Older adults with diabetes are at elevated risk of complications following hospitalization. Home health care services mitigate the risk of adverse events and facilitate a safe transition home. In the United States, when home health care services are prescribed, federal guidelines require they begin within two days of hospital discharge. This study examined the association between timing of home health care initiation and 30-day rehospitalization outcomes in a cohort of 786,734 Medicare beneficiaries following a diabetes-related index hospitalization. Of these patients, 26.6% were discharged to home health care. To evaluate the association between timing of home health care initiation and 30-day rehospitalizations, multivariate logistic regression models including patient demographics, clinical, geographic variables, and neighborhood socio-economic variables were used. Inverse probability-weighted propensity scores were incorporated into the analysis to account for potential confounding between the timing of home health care initiation and the outcome in the cohort. Compared to patients who received home health care within the recommended first two days, patients who received delayed services (3-7 days after discharge) had higher odds of rehospitalization (OR 1.28, 95% CI 1.25-1.32). Among patients who received late services (8-14 days after discharge), the odds of rehospitalization were four times greater than for patients receiving services within 2 days (OR 4.12, 95% CI 3.97-4.28). Timely initiation of home health care following diabetes-related hospitalizations is one strategy to improve outcomes.

With the increasing use of data-driven modeling methods new approaches to complex problems in the field of wind energy can be addressed. Topics reviewed through literature include wake modeling, performance monitoring and controls applications, condition monitoring and fault detection, and other data-driven research. Literature shows the advantages of data-driven methods reduce computational expense or complexity, particularly in the cases of wake modeling and controls, as well as various data-driven methodologies’ aptitude for predictive modeling and classification, as in the cases of fault detection and diagnosis. Significant work exists for fault detection while less work is found for controls applications. A methodology for creating data-driven wind turbine models for arbitrary performance parameters is proposed. Results are presented utilizing the methodology to create wind turbine models relating active adaptive twist to steady-state rotor thrust as a performance parameter of interest. Resulting models are evaluated by comparing root-mean-square-error (RMSE) on both the training and validation data sets, with Gaussian Process Regression (GPR), deemed an accurate model for this application. The resulting model undergoes particle swarm optimization to determine the optimal aerostructure twist shape at a given wind speed with respect to the modeled performance parameter, aerodynamic thrust load. The optimization process shows an improvement of 3.15% in thrust loading for the 10 MW reference turbine, and 2.66% for the 15 MW reference turbine.

The rapid transmission of COVID-19 in school communities has been a major concern. To ensure that mitigation systems were in place and support was available, a digital intervention to encourage and facilitate infection control behaviours was rapidly adapted and optimised for implementation as a whole school intervention. Using the person-based approach, ‘Germ Defence’ was iteratively adapted, guided by relevant literature, co-production with Patient and Public Involvement representatives, and think aloud interviews with forty-five school students, staff, and parents. Suggested infection control behaviours deemed feasible and acceptable by the majority of participants included handwashing/hand-sanitising and wearing a face covering in certain contexts such as crowded public spaces. Promoting a sense of collective responsibility was reported to increase motivation for the adoption of these behaviours. However, acceptability and willingness to implement recommended behaviours seemed to be influenced by participants’ perceptions of risk. Barriers to the implementation of recommended behaviours in school and at home primarily related to childcare needs and physical space. We conclude that it was possible to rapidly adapt Germ Defence to provide an acceptable resource to help mitigate against infection transmission within and from school settings. Adapted content was considered acceptable, persuasive, and accessible.

Daily maximum surface air temperature (Tamax) is a crucial factor for understanding complex land surface processes under rapid climate change. Remote detection of Tamax has widely relied on the empirical relationship between air temperature and land surface temperature (LST), a product derived from remote sensing. However, little is known about how such a relationship is affected by the high heterogeneity in landscapes and dynamics in seasonality. This study aims to advance our understanding of the roles of land cover and seasonal variation in the estimation of Tamax using the MODIS (Moderate Resolution Imaging Spectroradiometer) LST product. We developed statistical models to link Tamax and LST in the middle and lower reaches of the Yangtze River in China for five major land-cover types (i.e., forest, shrub, water, impervious surface, cropland, and grassland) and two seasons (i.e., growing season and non-growing season). Results show that the performance of modeling the Tamax-LST relationship was highly dependent on land cover and seasonal variation. Estimating Tamax over grasslands and water bodies achieved superior performance; while uncertainties were high over forested lands that contained extensive heterogeneity in species types, plant structure, and topography. We further found that all the land-cover specific models developed for the plant non-growing season outperformed the corresponding models developed for the growing season. Discrepancies in model performance mainly occurred in the vegetated areas (forest, cropland, and shrub), suggesting an important role of plant phenology in defining the statistical relationship between Tamax and LST. For impervious surfaces, the challenge of capturing the high spatial heterogeneity in urban settings using the low-resolution MODIS data made Tamax estimation a difficult task, which was especially true in the growing season.

Gas sensor arrays, also known as electronic noses, leverage a diverse set of materials to identify the components of complex gas mixtures. Metal-organic frameworks (MOFs) have emerged as promising materials for electronic noses due to their high-surface areas and chemical as well as structural tunability. Using our recently reported genetic algorithm design approach, we examined a set of 50 MOFs and searched through the over 1.125x1015 unique array combinations to identify optimal arrays for the detection of CO₂ in air. We found that despite individual MOFs having lower selectivity for O2 or N2 relative to CO₂, intelligently selecting the right combinations of MOFs enabled accurate prediction of the concentrations of all components in the mixture (i.e. CO₂, O₂, N₂). We also analyzed the physical properties of the elements in the arrays to develop an intuition for improving array design. Notably, we find that diversity among the surface areas in the MOFs leads to improved sensing. Consistent with the observation, we found that, as one might expect, the best arrays consistently had more structural diversity than the worst arrays.

Recent studies, typically using patient cerebrospinal fluid (CSF), have suggested that different autoantibodies (Aabs) acting on their respective receptors, may underlie neuropsychiatric disorders. The NR1 subunit of the N-methyl-D-aspartate receptor (NMDAR) has been identified as a target of anti-NMDAR Aabs in a number of central nervous system (CNS) diseases including encephalitis and autoimmune epilepsy. However, the role or the nature of Aabs responsible for effects on neuronal excitability and synaptic plasticity is yet to be established fully. Patient-derived anti-NMDAR Aabs have been shown to bind to specific regions within the NR1 subunit; here, peptide immunisation was used to generate Aabs against selected specific NR1 extracellular sequences. ‘Protein A’ purification was used to obtain total IgG and further peptide purification used to obtain a greater percentage of NMDAR-target specific IgG Aabs. Binding and specificity of these anti-NMDAR Aabs was determined using a range of methodologies including enzyme-linked immunosorbent assay, immunocytochemistry and immunoblotting. Functional effects were determined using different in vitro electrophysiology techniques: two-electrode voltage-clamp in Xenopus oocytes and measures of long-term potentiation (LTP) in ex vivo hippocampal brain slices using multi-electrode arrays. We show that anti-NMDAR Aabs generated from peptide immunisation had specificity for NR1 immunisation peptides as well as target-specific binding to the native protein. Anti-NMDAR Aabs had no clear effect on isolated NMDARs in an oocyte expression system. However, we show that peptide-purified anti-NMDAR Aabs prevented the induction of LTP at Schaffer collateral-CA1 synapses in ex vivo brain slices. Our data demonstrate that anti-NMDAR Aabs cause synaptic NMDAR hypofunction at a network level. This work provides a solid basis to address outstanding questions regarding anti-NMDAR Aabs mechanisms of action and, potentially, development of therapies against CNS diseases.

This work presents an innovative application of optimal control theory to the strategic scheduling of battery storage in the day-ahead electricity market, with a focus on enhancing profitability while factoring in battery degradation. The study incorporates in the optimisation framework the cost of battery capacity degradation, the effects of capacity degradation and internal resistance degradation into dynamics. We employ a continuous-time representation of the dynamics, in contrast with many other studies that use a discrete-time approximation with rather coarse intervals. We adopt an equivalent circuit model coupled with empirical degradation parameters to simulate a battery cell’s behaviour and degradation mechanisms with good support from experimental data. Utilising direct collocation methods with mesh refinement allows for precise numerical solutions to the complex, nonlinear dynamics involved. Through a detailed case study of Belgium’s day-ahead electricity market, we determine the optimal charging and discharging schedules under varying objectives: maximizing net revenues, profits considering capacity degradation, and profits considering both capacity degradation and internal resistance increase due to degradation. The results demonstrate the viability of our approach and underscore the significance of integrating degradation costs into the market strategy for battery operators, alongside its effects on the battery’s dynamic behaviour. Our methodology extends previous work by offering a more comprehensive model that empirically captures the intricacies of battery degradation, including a fine and adaptive time domain representation, focusing on the day-ahead market, and utilising accurate direct methods for optimal control. The paper concludes with insights into the potential of optimal control applications in energy markets and suggestions for future research avenues.

We argue for reconsidering leadership development based on systems design principles. A primary advantage of systems thinking is that it encourages holistic approaches to development and avoids episodic program-based training and piecemeal thinking. The latter approaches are both limited and limiting yet tend to be the preferred approach to leadership development in organizations. Systems approaches to development offer numerous advantages both conceptually and pragmatically, especially through the incorporation of ongoing feedback cycles. Core practices that define a leadership development system are presented and implications are discussed.

In the global carbon cycle, atmospheric carbon emissions, both ‘natural’ and anthropogenic, are balanced by carbon uptake (i.e. sequestration) that mostly occurs via photosynthesis, plus a much smaller proportion via geological processes. Since the formation of the Earth about 4.54 billion years ago the ratio between emitted and sequestered carbon has varied considerably with atmospheric CO₂ levels ranging from 100,000 ppm to a mere 100 ppm. Over this time, a huge amount of carbon has been sequestered due to photosynthesis and essentially removed from the cycle, being buried as fossil deposits of coal, oil and gas. Relatively low atmospheric CO₂ levels were the norm for the past 10 million years, and during the past million years they averaged about 220 ppm. More recently, the Holocene epoch, starting ~11,700 years ago, has been a period of unusual climatic stability with relatively warm, moist conditions and low atmospheric CO₂ levels of between 260 and 280 ppm. During the Holocene, stable conditions facilitated a social revolution with domestication of crops and livestock leading to urbanisation and development of complex technologies. As part of the latter process, immense quantities of sequestered fossil carbon have recently been used as energy sources, resulting in a particularly rapid increase in CO₂ emissions after 1950 CE to the current value of 424 ppm, with further rises to >800 ppm predicted by 2100. This is already perturbing the previously stable Holocene climate and threatening future food production and social stability. Today, the global carbon cycle has been shifted such that carbon sequestration is no longer keeping up with recent anthropogenic emissions. In order to address this imbalance it is important to understand the roles of high-capacity carbon sequestration systems, such as natural forests and tropical croplands, and to devise strategies to facilitate net CO₂ uptake.

Over the past two decades, persistent occurrences of harmful algal blooms (HAB; Karenia brevis) have been reported in Charlotte County, southwestern Florida. We developed data-driven models that rely on spatiotemporal remote sensing and field data to identify factors controlling HAB propagation, provide a same-day distribution (nowcasting), and forecast their occurrences up to three days in advance. We constructed multivariate regression models using historical HAB occurrences (213 events reported from January 2010 to October 2017) compiled by the Florida Fish and Wildlife Conservation Commission and validated the models against a subset (20%) of the reported historical events. The models were designed to specifically capture the onset of the HABs instead of those that developed days earlier and continued thereafter. A prototype of an early warning system was developed through a threefold exercise. The first step involved the automatic downloading and processing of daily Moderate Resolution Imaging Spectroradiometer (MODIS) Aqua products using SeaDAS ocean color processing software to extract temporal and spatial variations of remote sensing-based variables over the study area. The second step involved the development of a multivariate regression model for same-day mapping of HABs and similar subsequent models for forecasting HAB occurrences one, two, and three days in advance. Eleven remote sensing variables and two non-remote sensing variables were used as inputs for the generated models. In the third and final step, model outputs (same-day and forecasted distribution of HABs) were posted automatically on a web-based GIS (http://www.esrs.wmich.edu/webmap/bloom/). Our findings include the following: (1) the variables most indicative of the timing of bloom propagation are bathymetry, euphotic depth, wind direction, SST, chlorophyll-a [OC3M] and distance from the river mouth, and (2) the model predictions were 90% successful for same-day mapping and 65%, 72% and 71% for the one-, two- and three-day advance predictions, respectively. The adopted methodologies are reliable, dependent on readily available remote sensing data sets, and cost-effective and thus could potentially be used to map and forecast algal bloom occurrences in data-scarce regions.

The questions on who is entitled to benefit from REDD+ transactions remains one of the most controversially debated issues around cooperative efforts to reduce deforestation in developing countries. REDD+ has been conceived as international framework for voluntary efforts of developing countries to reduce greenhouse gas emissions and enhance carbon removals from forest activities. Designed as international framework under the UNFCCC that calculates emission reductions and removals (ERRs) at the national -and as an interim step on the subnational level – REDD+ is primarily a creature of international law. However, in defining forest-carbon ERRs the international framework competes with national emission trading systems and domestic REDD+ legislation as well as private standards that define units traded on the voluntary carbon market. The definition of various carbon units is closely linked to the question on who is entitled to participate in REDD+ and benefit from the sale of ERRs under results-based payment schemes or carbon market transactions. This paper applies a legal lens to the various claims to participate in REDD+ transactions. It tries to disentangle the various rights to ERRs, various carbon credits, and payments that come with REDD+ and that almost always create confusion and not seldom conflict around REDD+ implementation. The definition of carbon rights and the legal nature of carbon credits depends on local law and differs between countries. However, there are a number of legal considerations that apply and certain underlying concepts are relevant for the understanding of REDD+ transactions and the allocation of benefits and burdens of conservation activities.

Electricity load forecasting is a crucial undertaking within all the deregulated markets globally. In contemporary times, the transition from conventional electricity grids to Smart Grids constitutes an area where extensive research is conducted on a global scale. Among the research challenges, the investigation of Deep Transfer Learning (DTL) in the field of electricity load forecasting represents a fundamental effort that imparts generality to Artificial Intelligence applications, due to new capabilities, such as knowledge transfer and computational power reduction. In this paper a comprehensive study is conducted for day-ahead electricity load forecasting. For this purpose, three Sequence-to-Sequence (Seq2seq) Deep Learning (DL) models are used, namely the Multilayer Perceptron (MLP), the Convolutional Neural Network (CNN) and the Ensemble Learning Model (ELM), which is consisted of the weighted combination of the outputs of MLP and CNN models. Also, the study focuses on the development of different forecasting strategies based on DTL and emphasizing the way the datasets are trained and fine-tuning for higher forecasting accuracy. In order to implement the forecasting strategies using Deep Learning models, load datasets from three Greek islands, Rhodes, Lesvos, and Chios, are used. The main purpose is to apply DTL for day-ahead predictions (1-24 hours) for each month of the year for Chios dataset after training and fine-tuning the models using the datasets of the three islands in various combinations. After several trials, four DTL strategies are illustrated. In the first strategy (DTL Case 1), each of the three DL models is trained using only Lesvos dataset, while fine-tuning is performed on the dataset of Chios island, in order to create day-ahead predictions for Chios load. In the second strategy (DTL Case 2), data from both Lesvos and Rhodes concurrently are used for the DL model training period, and fine-tuning is performed on the data from Chios. The third DTL strategy (DTL Case 3) contains the training of the DL models using Lesvos dataset, and the testing period performed directly on the Chios dataset without fine-tuning. The fourth strategy is a Multi-task Deep Learning (MTDL) approach, which has been extensively studied in recent years. In MTDL, the three DL models are trained simultaneously on all three datasets and the final predictions are made on the unknown part of the dataset of Chios. In this paper, we explore the performance of DTL and compare the results with those produced with MTDL. The results demonstrated that DTL can be applied with high efficiency for day-ahead load forecasting. Specifically, the two cases with fine-tuning (DTL Case 1 and 2) outperformed MTDL in terms of load prediction accuracy. Regarding the DL models, all three exhibit very high prediction accuracy, especially in the two cases with fine-tuning. The ELM excels compared to the single models. More specifically, for conducting day-ahead predictions, it has been concluded that the MLP model presents best monthly forecasts with a MAPE of 6.24% and 6.01% for the first two cases, the CNN model presents best monthly forecasts with a MAPE of 5.57% and 5.60% respectively and the ELM model achieves best monthly forecasts with a MAPE of 5.29% and 5.31%, respectively, indicating the very high accuracy it can achieve.

The primary purpose of the study was the determination of the spatial day-to-day variability of extreme temperatures in Poland and the dependency of large temperature changes on atmospheric circulation in accordance with the Grosswetterlagen (GWL) classification. The goal was implemented based on data from 1966 to 2015, made available by the Institute of Meteorology and Water Management – National Research Institute. Day-to-day changes in maximum and minimum temperatures were designated with a rate of ≥ 6 °C (large) and with a rate of ≥ 12 °C (very large) and their spatial distribution was presented. Finally, the analysis of the dependency of considerable temperature changes on atmospheric circulation in accordance with the Grosswetterlagen (GWL) classification was conducted. The obtained results showed that in Poland in the period 1966-2015 the number of large changes in both Tmax and Tmin slightly increased, although the fluctuations show spatial variability. Large changes in Tmax occur more frequently in spring, and in Tmin in winter. Large changes in Tmax and Tmin are mainly recorded during cyclonic circulation, however, the anticyclonic circulation types favour especially large decreases in Tmin.

1) Background: Patients with neurological disorders are particularly at risk of falling and requiret functional rehabilitation. HUBER® is a motorised rotating platform that allows simultaneous work on balance, stability and strength with continuous adaptation and immediate feedback. This study aimed to measure the impact of rehabilitation with the HUBER® on the physical performance and quality of life of patients with neurological diseases requiring functional rehabilitation. 2) Methods: 32 subjects were enrolled in CHU Liège CNRF and randomly divided into 2 groups. The first group received classical rehabilitation combined with two training sessions per week on the HUBER® for 8 weeks. The second group received their usual treatment. This randomized control trial has been registered on clinicaltrials.gov under the number NCT04687293. Physical performance and quality of life were evaluated at different time. 3) Results: There was no significant difference between the 2 groups after enrolment. In terms of physical performance, an improvement in SPPB chair stand test (p=0.021) and total SPPB (p=0.003) was observed in the HUBER® group. In terms of quality of life, a higher improvement was observed overall in the HUBER® group (p<0.05 between groups). 4) Conclusion: The HUBER® showed promising results in functional rehabilitation of patients with neurological pathologies, as a complement to classical rehabilitation management by physiotherapy.

Rapidly and repeatedly ascertaining the health status of coral reefs is an ever more pressing issue as part of activities to understand and monitor the damaging impacts of climate change. A combination of increasing ocean temperatures, acidity and frequency of extreme storm events continues to alter the marine environment beyond what sensitive organisms, such as coral, can cope with. It is therefore vital to establish technologies and validated methods to provide a metric or indication into the health of these organisms. There are currently many surveys and techniques used by coral scientists to uncover insights into the status and assessment of coral reefs, from colour wheels to multispectral satellite surveys. Here we outline an array of current techniques and methods focused specifically on coral monitoring and health diagnosis, ranging across the length scales from simple diver-based surveyance to satellite remote sensing. The technique of using hyperspectral fluorescence imaging is also introduced as a viable novel addition to aid and extend the current toolbox of available technologies.

Most existing coal-fired power plants were designed for sustained operation at full load to maximize efficiency, reliability, and revenue, as well as to operate air pollution control devices at design conditions. Depending on plant type and design, these plants can adjust output within a fixed range in response to the plant operating or market conditions. The need for flexibility driven by increased penetration of variable and non-dispatchable power generation such as wind and solar is shifting the traditional mission profile of thermoelectric power plants in three ways: more frequent shutdowns when market or grid conditions warrant, more aggressive load ramp rates (rate of output change), and lower minimum sustainable load, which provides a wider operating range and helps avoid costly plant shutdowns. Recent studies have shown that flexibility of a coal-fired power plant can be improved by energy storage. The objective of this work was to analyze a set of energy storage options and determine their impact on flexibility and economics of a representative coal-fired power plant. The effect of three energy storage systems integrated with a coal power plant on plant flexibility and economics was investigated. The results obtained in this project show that Energy Storage Systems integrated with a thermal power plant improves plant flexibility and participation in the Energy and Ancillary Services markets which improves plant financial performance. The study was funded by the U.S. Department Office of Fossil Energy FE-1 under Award Number DE-FE0031903.

The month of May 2024 was characterized by solar energetic particles events directed towards the Earth, especially the big event causing a strong terrestrial geomagnetic storm during the night from 10 to 11 May 2024, with auroras observed everywhere in Europe. This was the strongest storm for the last 20 years with a Dst < -400 nT. In the present work, we show with observations of GOES, PROBA-V/EPT and MetOP/MEPED that this exceptional event was associated with the injection of energetic protons in the proton radiation belt, with important consequences for the South part of the South Atlantic Anomaly (SAA). In addition, the geomagnetic storm caused by the solar eruption has had tremendous impacts on the electron radiation belts. Indeed, we show that for 0.3 to 1 MeV electrons, the storm led to a long lasting four belts configuration which was not observed before with EPT launched in 2013, until a smaller geomagnetic storm on June 15 took place. Moreover, for the first time since its launch, observations of the EPT show that ultra-relativistic electrons with E>2 MeV have been injected into the inner belt until L=2.4, violating the impenetrable barrier previously estimated to be located at L=2.8.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer care and shown remarkable efficacy clinically. This efficacy is, however, limited to subsets of patients with significant infiltration of lymphocytes into the tumor microenvironment. To extend their efficacy to patients who fail to respond or achieve durable responses, it is now becoming evident that complex combinations of immunomodulatory agents may be required to extend efficacy to patients with immunologically “cold” tumours. Oncolytic viruses (OVs) have the capacity to selectively replicate within and kill tumour cells resulting in the induction of immunogenic cell death and the augmentation of anti-tumour immunity and have emerged as a promising modality for combination therapy to overcome the limitations seen with ICIs. Pre-clinical and clinical data has demonstrated that OVs can increase immune cell infiltration into the tumour and induce anti-tumour immunity, thus changing a “cold” tumour microenvironment that is commonly associated with poor response to ICIs, to a “hot” microenvironment which can render patients more susceptible to ICIs. Here, we review the major viral vector platforms used in OV clinical trials, their success when used as a monotherapy and when combined with adjuvant ICIs, as well as pre-clinical studies looking at the effectiveness of encoding OVs to deliver ICIs locally to the tumour microenvironment through transgene expression.

Recommender Systems (RecSys) are crucial in managing information overload and enhancing user satisfaction across various digital platforms, including e-commerce and entertainment. Evolving from traditional models to Deep Neural Networks (DNNs) and, more recently, Large Language Models (LLMs), these systems leverage sophisticated algorithms to analyze user behaviors and preferences. LLMs, such as GPT-4, are trained on extensive datasets to comprehend and generate natural language, significantly advancing their ability to deliver personalized recommendations. This tutorial explores the transformative impact of LLMs on RecSys, discussing their development, application in handling complex datasets, and the integration of contextual insights. Real-world examples illustrate how LLMs enhance recommendation accuracy and user experience, highlighting challenges and future directions in the field.

. The Tau protein is associated with microtubule function in the neuron and is crucial for normal axonal transport. In several different neurodegenerative disorders, Tau misfolding leads to hyper-phosphorylation (p-Tau) and intracellular p-Tau aggregates known as neurofibrillary tangles (NFTs). This is particularly evident in individuals with Down syndrome (DS), who develop Alzheimer’s disease-like (AD) neuropathology early in life with almost complete penetrance, associated with the development of dementia symptoms in their 40s or 50s. Our previous findings have shown that certain forms of p-Tau are present already in childhood in individuals with DS in neuron-derived exosomes, suggesting an early phosphorylation profile in this population that could influence the development of AD pathology. Misfolded p-Tau isoforms are known to be seeding competent and may be responsible for spreading AD pathology in different regions of the brain. This review is focused on the accumulation of p-Tau in the brain of individuals with DS and potential consequences for brain function.

Legionella bacteria can proliferate in poorly maintained water systems, posing risks to users. All Legionella species are potentially pathogenic but Legionella pneumophila (L. pneumophila) is usually the primary focus of testing. However, Legionella anisa (L. anisa) also colonises water distribution systems, is frequently found with L. pneumophila and could be a good indicator for increased risk of nosocomial infection. Anonymized data from three commercial Legionella testing laboratories afforded analysis of 565,750 water samples. Data covered July 2019 to August 2021, including the COVID-19 pandemic. Results confirmed L. anisa commonly colonises water distribution systems, being the most frequently identified non-L. pneumophila species. Proportions of L. anisa and L. pneumophila generally remained similar but increases in L. pneumophila during COVID-19 lockdown suggests static water supplies might favour its growth. Disinfection of hospital water systems was effective but re-colonization did occur, appearing to favour L. pneumophila, although L. anisa colony numbers also increased as a proportion of the total. While L. pneumophila remains the main species of concern as a risk to human health, L. anisa’s role should not be under-estimated, either as a potential infection risk or as an indicator of the need to intervene to control Legionella colonization of water supplies.

There is a growing consensus that to effectively adapt to climate change, cities need user-friendly tools and reliable high-resolution biophysical and socio-economic data for analysis, mapping, modeling, and visualization. This study examines availability of various types of information used in climate adaptation plans of 40 municipalities with population less than 300,000 people in the United and in France, probing into the choice and usage of relevant information by small municipalities. We argue that non-climatic spatial data, such as population demographic and socio-economic patterns, urban infrastructure, and environmental data must be integrated with climate tools and datasets to inform effective vulnerability assessment and equitable climate adaptation planning goals. Climate adaptation plans frequently fail to address the existing structural inequalities and environmental injustices in urban infrastructure and land use. Adaptation methodological approaches should be reassessed in the context of much needed societal transformation. Lessons learned from our studies offer valuable insights for potential development of the national and state-level climate adaptation information services for cities.

Observations of the X-ray binary system Her X-1 by the AstroSat Soft X-ray Telescope 1 (SXT) were carried out in 2020 through 2023 with the goals of measuring X-ray spectrum changes with the 35-day disk rotation phase and measuring eclipses at different 35-day phases. The four multi-day long observations were scheduled during: turn-on to Main High (MH) and MH rise; MH state; Short High (SH) state; and Low State (LS). 35-day phase was determined using monitoring observations with the Swift Burst Alert Telescope (BAT). Nine eclipses were observed at a range of 35-day phases, with at least one eclipse during each observation. Data with dips were separated from data without dips. The variation of X-ray spectral parameters vs. 35-day phase shows the following: eclipse parameters are nearly constant, showing that the scattering corona does not change with 35-day phase; dips show an increase in covering fraction but not column density compared to non-dip data; the 1 keV line normalization indicates an origin in a small region near the continuum emission region, likely the magnetospheric accretion flow from the inner disk onto the neutron star; and the change in blackbody normalization (area) shows that the emission region is much larger than the 1 keV emission region, and consistent with the inner edge of the accretion disk.

In recent years, the global energy sector has seen significant transformation, particularly in Europe, with a notable increase in intermittent renewable energy integration. Italy and the European Union (EU) have been among the leaders in this transition, with renewables playing a substantial role in electricity generation as of mid-2020s. The adoption of Battery Energy Storage Systems (BESS) has become crucial for enhancing grid efficiency, sustainability, and reliability by addressing the intermittent renewable sources. This paper investigates the feasibility and economic viability of batteries into wholesale electricity markets as per EU regulation, focusing on the dynamics of very different markets, namely the Day-Ahead Market (DAM) based on system marginal price and the Cross-Border Intra-day Market (XBID) based on continuous trading. A novel model is proposed to enhance BESS operations, leveraging price arbitrage strategies based on zonal price predictions, levelized cost of storage (LCOS), and uncertain bid acceptance in continuous trading. Machine learning and deep learning techniques are applied for price forecasting and bid acceptance prediction, respectively. The study finds that data-driven techniques outperform reference models in price forecasting and bid acceptance prediction (+7-14% accuracy). Regarding market dynamics, the study reveals a higher competitiveness of the continuous market compared to the DAM, particularly with increased risk factor in bids leading to higher profits. This research provides insights into compatibility between continuous markets and BESS, showing substantial improvements in economic profitability and the correlation between risk and profits in the bidding strategy (+9 M€ yearly revenues are obtained with a strategic behavior that reduces by 60% awarded energy).

Artificial intelligence (AI) systems are poised to become deeply integrated into society. If developed responsibly, AI has potential to benefit humanity immensely. However, it also poses a range of risks, including risks of catastrophic accidents. It is crucial that we develop oversight mechanisms that prevent harm. This article outlines a framework for evaluating and auditing AI to provide assurance of responsible development and deployment, focusing on catastrophic risks. We argue that responsible AI development requires comprehensive auditing that is proportional to AI systems’ capabilities and available affordances. This framework offers recommendations toward that goal and may be useful in the design of AI auditing and governance regimes.

Tamil Nadu, a state in southern India, is bereft of any native milch or dual-purpose cattle breed and the state depends chiefly on crossbred cattle for milk production. As most (90 percent) of the milk production in the state was contributed by Jersey crossbred cattle, the genetic evaluation study was intended to assess the milk production traits viz., test-day milk yields (TDMYs), total milk yield (TMY) and 305-day milk yield (305MY) in these crossbred cattle reared under farmers’ rearing environment. Data on monthly TDMYs (TDMY1 to TDMY10) of Jersey crossbred cows (n=81,653) reared by the farmers over 24 years (1999-2022) were collected for evaluation. The influence of non-genetic factors viz., location (agroclimatic zones), period and season of calving, and parity on TDMYs, TMY, and 305MY were assessed, and the variance and covariance components for genetic parameters (heritability and genetic correlation) of the traits were estimated by the method of restricted maximum likelihood (REML) under multivariate animal model and by random regression model (RRM). The overall means of various TDMYs ranged from 4.98 (TDMY10) to 9.95 kg (TDMY2) and, for TMY and 305MY the means were 2480.33 and 2393.71 kg respectively. The heritabilities estimated by animal model for TDMYs were high and ranged from 0.39 ± 0.01 to 0.47 ± 0.01 and were fairly less variable throughout the lactation while the estimates obtained by RRM were medium to high and ranged between 0.28 ± 0.01 and 0.65 ± 0.02 for different days in milk (DIMs). The heritability estimated for TMY and 305MY were 0.48 ± 0.01 and 0.49 ± 0.01 respectively. The estimates of heritability in mid-lactation yields were comparatively little less than those at the beginning and the end of lactation. The high estimates of heritabilities for TDMYs, TMY, and 305MY obtained in the present study offered an ample scope for improving milk production through selective breeding. Genetic correlations between TDMYs estimated by animal model were positive and moderate to high, with a range between 0.47 ± 0.01 and 0.99 ± 0.00. Considerably higher estimates (0.97-0.99) were observed between adjacent TDMYs showing strong genetic associations. By RRM, genetic correlations estimated between DIMs were positive, except for a few estimates and the magnitude of genetic correlation decreased with an increase in the interval between the DIMs. The high genetic correlation observed between the TDMYs in early and mid stages of lactation with TMY and 305MY suggested that these test day yields could be used favorably for the early selection of cows for milk production which facilitates reduction in the generation interval and consequently increase the annual genetic gain for the milk production traits.

The objectives of this study was to assess the impact of a reproductive approach in high-yielding nulliparous and parous Holstein cows on the interestrus interval, estrus detection rates, conception rates, and pregnancy rates. The strategy involved giving GnRH on day 5 following artificial insemination (AI). For nulliparous cows, there appears to be no noticeable effect of GnRH therapy on the interestrus interval. In both groups, nearly all of the cows exhibited an 18–25-day cycle interval (P < 0.05). In the 18–25 day cycle period, the untreated multiparous cows exhibited the highest proportion (P < 0.05), while the treated group demonstrated the highest proportion (P < 0.05) in the 26–35 day cycle interval. The study found that the conception rate was higher in repeat breeder nulliparous and 3+ lactation treated Holstein cows compared with untreated ones. However, the cumulative heat detection rate, pregnancy rate and conception rates were similar in both groups (P > 0.05). Also, this study found that in the hottest months of the year, this therapeutic approach can't counteract the negative effect of heat stress in high-yielding dairy cows. Thus, it is not advised of using the hormonal method to create supplementary corpus luteum across the herd.

The increasing complexity of vehicular traffic and the prevalence of accidents, particularly rear-end collisions, necessitate enhancements in automotive safety technologies. Adilights, an innovative automotive lighting system, addresses this need by introducing a dynamic visual communication method between vehicles. This system features a novel design that employs variable-intensity brake lights configured in an upside-down "U" shape to indicate braking severity. The intensity and pattern of the lights change in response to the pressure applied to the brake pedal, providing clear and immediate feedback to following drivers. This design not only improves the perceptibility of braking signals, particularly in dense traffic and poor visibility conditions but also aims to reduce the frequency of rear-end collisions significantly. The paper details the development and testing of Adilights, discusses its integration with current vehicular systems, and evaluates its effectiveness through simulated scenarios. The introduction of Adilights marks a step forward in the use of adaptive lighting systems for enhanced vehicular communication and road safety.\cite{Lee2007RearEnd}

Global stress is widespread in todays post-pandemic world of political and economic uncertainty. Vibroacoustic technology is a vibrotactile intervention with multiple uses, and its impact on stress lacks interpretation. This research assessed if the vibroacoustic technology of a Vibroacoustic Sound Massage (VSM) can reduce psychological, physiological and cognitive stress. The Perceived Stress Scale (PSS-10), and electrocardiogram (ECG) and electroencephalogram (EEG) biosignals were used to quantify results. Participants were divided into Low Stress and High Stress groups. ECG results show VSM increased parasympathetic activity for all participants, with the Low Stress group more effected. EEG results indicate increased concentration (TBR), reduced arousal and increased relaxation (BAR), and non-significant effects on participant well-being (FAA), though variability in this metric was homogenised after VSM. Together, these results validate VSM as an effective support tool for stress management and further research is required.

Monitoring the health of coral reefs is essential to understand the damaging impacts of anthropo-genic climate change. Non-invasive methods to survey coral reefs are the most desirable and op-tics-based surveys, ranging from simple photography to multispectral satellite imaging are well es-tablished. Herein, we review these techniques, focusing on their value for coral monitoring and health diagnosis. A new, low-cost hyperspectral imaging technique using linear variable filters is also described. This system is capable of simultaneously producing hyperspectral and photogrammetric outputs, which provides integrated information of reef structure and physiology.

Complex problem-solving (CPS) tasks have become an increasingly popular tool for understand-ing and assessing cognitive ability. These tasks have been repeatedly shown to be predictors of academic and workplace success above and beyond traditional measures of general intelligence and fluid intelligence. To date, there has been little exploration of the underlying mechanisms that drive this additional predictive utility. In this study, we examined the role of a variety of non-cognitive personality and investment traits that could drive performance on CPS tasks. Adult participants (n = 152) were recruited via M-Turk and completed a battery of personality and in-vestment trait measures, a measure of general mental ability, and a 61-trial microworlds-style CPS task. Generalised linear mixed-effects models revealed a wide variety of personality and in-vestment traits influenced task performance above and beyond general mental ability. Specifical-ly, two clusters of traits emerged as important determinants of performance: one cluster that in-fluenced the capacity to deal with the introduction of system randomness (Conscientiousness and Extraversion) and one cluster that influenced the capacity to deal with the introduction of system delays (NFC, Learning Goal Orientation, and Intellect). These findings suggest that CPS tasks do capture more than just general mental ability and may be good predictors of academic and workplace success because they tap into both cognitive ability and the motivation and willingness to engage in cognitive exploration and mental effort.

1. Background Septic shock is a rare and serious infectious disease. Patients surviving the early phase are at high risk of multiple amputations of limbs. They are potential sources of serious disability. 2. Methods The objective was to describe the functional prognosis and quality of life of the four-limb amputee patients following septic shock. This is a descriptive, retrospective and mono-centric study. The patients included between 2010 and 2019 had septic shock after 18 years, responsible for amputation of the four limbs. We studied the mean age of septic shock, the causative organisms, the infectious door enter, the different levels of amputation, the fitting process, the resumption of walking, the Functional Independence Measure (FIM) and the SF-12 Quality of Life Questionnaire. 3. Results We suceed to include 15 patients.. 53.3% women and 46.7% men with an average age of 46.1 years. 80% presented bilateral trans-tibial amputations, all were able to return walking even over short distances, within an average of 8.4 months. 40% did not require a technical walking aid, 33.3% had no walking perimeter limitation. 47% had a higher mental and social quality of life score than the general population. The younger the patients, the better their physical quality of life. After two years of follow-up, the younger the patients, the better their functional autonomy. Patients with better functional autonomy had a better physical quality of life. 4. Conclusion The number of amputations due to spetic shock is likely to increase in the years to come throughout the world. Our study prove that quadri-amputee patient can regain a fully acceptable functional and quality of life being monitored in a specialized health center with multidisciplinary health professional to help him.

Zero-day threats are a more severe and constantly developing menace to various participants including large companies, government offices, and educational establishments. These entities may contain valuable information and essential operations that attract cyber attackers. These exploits are especially devastating as they target weaknesses that an organization’s vendors are not even aware of, making them have no protection against them. This paper focuses on the background and use of zero-day exploitation and the structure and technologies of these complex malware attacks. We examine two notable real-life cases: the case of ‘HAFNIUM targeting Exchange Servers with zero-day exploits’ that was investigated by Microsoft 365 Security and Microsoft Threat Intelligence, and the ‘Log4j vulnerability’ case that was reported by the National Cyber Security Centre. These cases show the critical effects of zero-day vulnerabilities and measures taken to combat them. Additionally, this paper outlines different strategies that can be used to prevent zero-day attacks with the help of modern technologies. These are fast patch release, effective IDS/IPS, and a security model that involves constant vigilance and use of behavioral analytics. Thus, by studying the lifecycle of zero-day vulnerabilities and the structure of the exploits, one can enhance the protection of the organization against the threats that are invisible to traditional security systems. This extensive survey is designed to be useful in understanding the characteristics of zero-day vulnerabilities, the technologies for their mitigation, and the constant threat and development in the field of cybersecurity. Thus, it is possible to strengthen the protection against these threats that are constant and develop with time by analyzing the previous events and predicting potential problems.

Despite increased hurricane intensity, the U.S. Gulf of Mexico coast has experienced dramatic coastal population increase of 24.5% from 2000 to 2016. However, in coastal Louisiana areas with dramatic wetland loss, parishes have experienced population declines and lower rates of population growth. Therefore, understanding the magnitude of the effect of wetland loss as a main driver in population loss in coastal Louisiana is critical. Using regression analysis, this study finds that wetland loss has a significant and persistent negative effect on population growth in coastal Louisiana. This effect resulted in a reduction in the population growth rate in coastal parishes over time. A counterfactual simulation was conducted to estimate the potential population size in the absence of wetland loss from 1990 to 2021. On average, the effect of 1 hectare of wetland lost causes a reduction of approximately 1000 persons. This indicates that for the year 2021, the population was approximately 18% lower than the population that would have existed in the absence of wetland loss. This research underscores the role of wetlands in providing direct and indirect benefits to people in coastal Louisiana that are ultimately reflected in its population levels.

The need to alleviate the difficulties of abstraction and improve students’ achievement in Physical Geography informed this research. This study investigated the Effects of Mastery Learning Strategy and Learning Retention on Senior Secondary School Students’ Achievement in Physical Geography. The study adopted the quasi experimental non-equivalent pre-test, post-test control group design. The Multi-stage sampling technique at four levels was used to select four co-educational secondary schools in Ganye Educational Zone in Nigeria. The sample for the study was 218 Senior Secondary School two (SS II) students offering Geography from four intact classes in the four selected secondary schools. The instrument used for data collection was “Physical Geography Achievement and Retention Test” (PGART). The reliability of the instrument was established using Kendall tau b statistic. This gave a reliability index of 0.74. Data collected were analyzed using Mann-Whitney U and t-Test. The results showed that Mastery Learning Strategy has the potentials to improve students’ learning outcomes, retention and achievement in all spheres of cognitive domain in Physical Geography better than the Conventional Method. Hence the need to incorporate this teaching strategy during instruction so that learners would be guided to learn meaningfully and be assisted to retain content learnt in Geography.

The vaccine industry has undoubtedly contributed massively in the medical world, with hundreds of millions of lives saved as a result of the successful development of prophylactic and therapeutic vaccines against various infectious and oncological diseases. Simultaneously, there has been an ongoing evolutionary battle between polymorphic microbes and the human immune system, and various microbes have developed counter-responses against the human host immune system, by creating diverse “holes” of vulnerability in the innate immune system. Such mechanisms may have resulted due to the lower prophylactic and therapeutic focus upon sharpening the innate immune lines as directly as necessary. The overall objective of vaccine-development should be the sharpening of all immune departments that are targeted by various microbial agents for the purpose of transient innate immune suppression and the distribution of the microbial count/load at a systemic level. Likewise, it could be viable for the clinical research community to start focusing upon filling in the “gaps” of vulnerability that are now present in the pathways responsible for the proper natural immune activation and proportionate signalling toward the adaptive immune system. Perhaps, through such a process, the “road” toward the adaptive immune system, which is “old” and filled with “holes”, could be gradually transformed into a perfectly uniform “highway”, with all the required signals transmitted robustly from the innate to the adaptive immune system, before microbes manage to translate the various pathogenic proteins that transiently prevent such transmission altogether, until it becomes too late for the immune response to possibly develop in a proportionate and non-harmful manner to the organism. Such a scenario would be possible, given that it is almost impossible for human evolutionary growth to eventually stall and not risk experiencing a decrease as a result. Simultaneously, it is important for human society to bind by the principles of maintaining a healthy and nature-friendly lifestyle, given the philosophical quote of “We are what we eat.” The overall objective should be the facilitation of human and animal immune evolution over viral and bacterial molecular self-camouflaging from all possible directions, as a sharper human and animal evolutionary growth resulting from such actions could “cost” the sharper evolutionary growth of microbes as such, given that evolutionary patterns are based upon the models observed in Physics, in Newton’s Third Law of Motion, as well as in the First Law of Thermodynamics, which concerns the Conservation of Energy.

Abstract: Introduction: A retrospective case-controlled study was performed to evaluate the out-comes of shoulder arthroplasty performed as a day case in carefully selected patients, compared to the traditional inpatient approach. Materials & Methods: Patients who had total or hemiarthro-plasty of the shoulder performed as a day case or inpatient procedure were recruited. The primary outcome compared rates of uneventful recovery, defined by the absence of any complications or readmission to hospital within six months of surgery, between Inpatient and Outpatient groups. Secondary outcomes included examiner-determined functional scores and patient-determined pain scores at one, six, twelve, and twenty-four weeks post-surgery. A further assessment of pa-tient determined pain scores was carried out at a minimum of two years post-surgery (5.8 ± 3.2). Results: 73 patients (36 Inpatients and 37 Outpatients) were included in the study. Within this time frame 25/36 inpatients (69%) had uneventful recoveries compared to 24/37 outpatients (65%) (p = 0.17). Outpatients showed significant improvement over pre-operative baseline levels in more of the secondary outcomes (strength and passive range-of-motion) by six months post-operation. Outpatients also performed significantly better than Inpatients in external rotation (p<0.05) and internal rotation (p=0.05) at six-weeks post-surgery. Both groups showed significant improvement compared to pre-operative baselines in all patient-determined secondary outcomes except level of activity at work and sport. Inpatients, however, less severe pain at rest at six weeks (p=0.03), sig-nificantly less frequent pain at night (p=0.03) and extreme pain (p=0.04) at 24 weeks; and less se-vere pain at night at 24 weeks (p<0.01). By minimum two years postoperation, inpatients were more comfortable repeating their treatment setting for future arthroplasty (16/18) compared to outpatients (7/22) (p = 0.0002). Conclusions: At a minimum of two years follow up, there were no significant differences in rates of complications, hospitalisations, or revision surgeries between pa-tients that underwent shoulder arthroplasty as an inpatient versus as an outpatient. Outpatients demonstrated superior functional outcomes but reported more pain at six months post-surgery. Patients in both groups expressed a preference for inpatient shoulder arthroplasty in future. What is Known About This Subject: Shoulder arthroplasty is a complex procedure, and has tradition-ally been performed on an inpatient basis, with patients admitted for six to seven days post-surgery. One of the primary reasons for this is the high level of postoperative pain, usually treated with hospital-based opioid therapy. Two studies demonstrated outpatient TSA to have a similar rate of complications as inpatient TSA, however these studies only examined patients within a shorter term 90 day postoperative period, and did not evaluate functional outcomes between the two groups or in the longer term. What This Study Adds to Existing Knowledge: This study provides evidence supporting the longer-term results of shoulder arthroplasty done as a day case in carefully selected patients, which are comparable to outcomes in patients that are admitted to hospital post-surgery.

Bodybuilders utilize peaking strategies in a bid to fine-tune their aesthetics for competition day. The most prevalent peaking strategies utilized by natural bodybuilders are unreported in the current literature. Eighty-one (M - 59, F - 22) natural bodybuilders were recruited from competitions during the 2016 and 2017 British Natural Bodybuilder Federation seasons. Competitors completed a 34-item questionnaire designed to investigate peaking and contest day strategies. The questionnaire listed commonly utilized peaking strategies and provided additional space for qualitative information. Analysis of the data indicated that carbohydrate (CHO), water and sodium manipulation were the most commonly utilized peak week strategies. The consumption of high glycemic index CHO was the most common competition day strategy. Only 6.2 % of competitors reported following their regular diet the week prior to competition. The CHO manipulation strategies were similar to classical CHO loading, whereby bodybuilders attempt to maximize muscle glycogen concentrations. Furthermore, bodybuilders attempted to remove superfluous water by exploiting the diuretic/polyuria effect associated with water loading/restriction. The potentially deleterious effects of peaking on bodybuilders' health is considered and the efficacy of these strategies to enhance appearance is discussed. The findings of the present investigation are likely to be of interest to bodybuilders and their coaches.

Purpose: To compare the therapeutic efficacy and safety of dorzolamide/timolol fixed-combination in newly diagnosed primary open angle glaucoma patients. Methods: In this prospective, interventional case series, newly diagnosed primary open angle glaucoma (POAG) patients that had not been treated for glaucoma were included. Patients were started on Cosopt twice a day (BID) for 1 month and then switched to three times a day (TDS) for additional 1 month. Patients underwent comprehensive ophthalmic examination, diurnal intraocular pressure (IOP), blood pressure (BP) and 24-hours heart rate (HR) measurements at baseline, month 1( BID), and month 2( TDS). IOP, systolic and diastolic pressures were measured at 8:00 AM,12:00 AM, 4:00 PM, 8:00 PM and 12:00 PM. Throughout the study, all adverse events were recorded and monitored by the investigators. Results: In 31 POAG patients that completed the study ,mean baseline IOP was 23.1±3.15 mmHg . IOP was decreased significantly 16.5 ± 2.21 at 1 month (P < 0.0001) and 13.9 ± 2.23 mmHg at 1 and 2 month follow up. (P < 0.0001) IOP was significantly lower in month 2 compared to month 1 (P = 0.0004). While Cosopt BID significantly reduced the mean 24-hour systolic BP and mean 24-hour HR from baseline (P < 0.0001), the mean 24-hour systolic BP and HR remained unchanged 2ith Cosopt TDS compared to BID (P = 0.62). Conclusions: Cosopt TDS has a superior IOP-lowering effect than Cosopt BID in POAG patients with comparable safety profile.

The study of precipitation amount at different time scales constitutes an important issue in climate research and risk assessment. When dealing with daily totals, a frequent but sometimes underestimated problem is at what time the observation day begins. The choice of different starting times may lead to incompatibility between stations and incorrect identification of extreme events. In this work, the problem of temporal misalignment between precipitation datasets characterized by different starting time of the observation day is analyzed. The most widely used adjustment methods (1day and uniform shift) and two methods based on reanalysis (NOAA and ERA5) are evaluated in terms of temporal alignment, precipitation statistics and percentile distributions. As test series, the precipitation amount collected from 9 a.m. local time (09 LT) on the previous day to 09 LT on the target day (9-9 datasets) of the Padua and nearby stations in the period 1993-2022 have been selected. Results show that the reanalysis-based methods, in particular ERA5, outperform the others in temporal alignment, regardless the station. But, for the periods in which reanalysis data are not available, “1day” method, which shifts the daily amount back one calendar day, and “unif” method, which distributes uniformly the daily total from a 2-day moving window surrounding the target date, can be considered valid alternatives. On the other side, concerning the precipitation statistics, the reanalysis-based methods are not the best option, as they increase the precipitation frequency and reduce the mean value over wet days, NOAA much more than ERA5. Nevertheless, the uniform method provides a larger deviation from the original daily series. The use of the series of a station nearby the target one, which is mandatory in case of missing data, gives similar or better results than applying any adjustment method to the 9-9 series. General conclusions can hardly be drawn as they depend on the method and station. For the Padua dataset, the analysis was repeated at monthly and seasonal resolution. In general, the adjustment series show the most relevant changes in the precipitation statistics in summer and less temporal alignment with the original series in summer and autumn, the two seasons mainly affected by heavy rains in Padua. Finally, the percentiles distribution, analyzed for all the methods and stations, indicates that any adjustment method underestimates the percentile values, except ERA5. Only Legnaro, the station most correlated with Padua, gives results like ERA5.

HIV-1 assembly is a complex mechanism taking place at the plasma membrane of the host cell. It requires nice spatial and temporal coordination to end up with a full immature virus. Researchers have extensively studied HIV-1 assembly molecular mechanism during the past decades, in order to dissect the respective roles of viral proteins, viral genome and host cell factors. Nevertheless, the time course of the process has been observed in living cells only a decade ago. The very recent revolution of optical microscopy, combining high speed and high spatial resolution now permit to study assemblies and their consequences at the single molecule level within (living) cells. In this review, after a short description of these new approaches, we will show how HIV-1 assembly in cells has been revisited using these advanced super resolution microscopy techniques and how much it could make a bridge in studying assembly from the single molecule to the host cell.

Contemporary climate change is exposing plant populations to novel combinations of temperatures, drought stress, [CO₂] and other abiotic and biotic conditions. These changes are rapidly disrupting the evolutionary dynamics of plants. Despite the multifactorial nature of climate change, most studies typically manipulate only one climatic factor. In this opinion piece, we seek to explore how climate change factors interact with each other and with biotic pressures to alter evolutionary processes. We first explore the ramifications of climate change for key life history stages (germination, growth and reproduction). We then examine how mating system variation influences population persistence under rapid environmental change and propose that mixed mating could be advantageous in future climates. Furthermore, we discuss how spatial and temporal mismatches between plants and their mutualists and antagonists could promote or constrain adaptive responses to climate change. For example, plant-virus interactions vary from highly pathogenic to mildly facilitative, and are partly mediated by temperature, moisture availability and [CO₂]. Will host plants exposed to novel, stressful abiotic conditions be more susceptible to viral pathogens? Finally, we propose novel experimental approaches that could illuminate how plants will cope with unprecedented global change, such as resurrection studies combined with experimental evolution, genomics or epigenetics.

Background and Objective: Patients with spinal muscular atrophy (SMA) treated with a dis-ease-modifying therapy (DMT) are often classified as responders or non-responders based on at-tainment of a specific improvement threshold on validated functional scales. This categorization may significantly impact treatment reimbursement in some countries. The aim of this research is to evaluate the perception of treatment benefit by patients considered as responder or non-responder. Methods: In this non-commercial multicenter study, 99 post-symptomatically treated SMA type I-III patients with a median age of 11.2 (0.39-57.4) years at treatment initiation were stratified into three groups based on their treatment outcomes, i.e. those exhibiting clinically significant improvement (N=41), those with non-clinically significant improvement (N=18), or those show-ing no improvement (N=40). Fifteen months after treatment initiation patients or patients’ care-givers were assessed using a patient-rated scoring system based on the Patient Global Impression of Change (PGIC) scale, comprising 22 questions targeting important aspects and tasks in the daily life of patients with SMA. Results: We found no statistical difference in patient perception of treatment benefit in 17 out of 22 domains across patient groups. Conclusion: Our results suggest that functional motor scales do not recapitulate patients and pa-tients’ caregivers experience about the effect of nusinersen treatment in SMA.

Retinitis pigmentosa (RP) is a frequent cause of blindness among the working population in industrial countries, due to the inheritable death of photoreceptors. Though a gene therapy was recently approved for mutations in the RPE65 gene, there is generally no effective treatment presently. Previously, abnormally high-level cGMP and overactivation of its dependent protein kinase (PKG) have been suggested as causative for the fatal effects on photoreceptors, making it meaningful to explore the cGMP-PKG downstream signaling for more pathological insights and novel therapeutic target development purposes. Here we manipulated the cGMP-PKG system in degenerating retinas from the rd1 mouse model pharmacologically via adding a PKG inhibitory cGMP-analogue to organotypic retinal explant cultures. A combination of phosphorylated peptides enrichment and mass spectrometry was then applied to study the cGMP-PKG-dependent phosphoproteomics. We identified a host of novel potential cGMP-PKG downstream substrates and related kinases using this approach, and selected the RAF1 protein, which may act as both a substrate and a kinase, for further validation. We showed that the RAS/RAF1/MAPK/ERK pathway may be involved in retinal degeneration in a yet unclarified mechanism, thus deserving further investigation in the future.

Background: Infectious disease is a major challenge in aquaculture and poses a constraint for development of farming of new species. In 2017, Siberian sturgeon (Acipenser baerii) juveniles were imported from Italy to a Swedish farm. Due to stressful conditions, 30% died during transport and in the first days after arrival. Ten days after arrival, mortalities started to occur again. Within two months, only 5% of the juveniles were still alive. Methods: Diseased fish were transported live to the National Veterinary Institute (SVA) for necropsy and further analysis. Pathological and histopathological investigation was conducted. Virology was performed on gills and internal organs by cell culture isolation and specific PCR protocols. Results: The juveniles displayed neurological signs such as lethargy, inability to maintain upright position and erratic swimming. Body condition was low. Gills were pale. One fish had petechial hemorrhage on the abdomen and the snout. The ventricles were air-filled with, but swim bladders were deflated. One specimen had intestinal hemorrhage. Viral cell cultures were negative, but PCR of gills and internal organs detected the presence of Acipenser Iridovirus European (AcIV-E). Conclusions: AcIV-E was associated with disease and high mortality in the sturgeon juveniles. Stress probably aggravated the course of the infection.

The circadian clock is a 24-hour cycle within the body that regulates various factors, including sleep, body temperature, and hormone secretion. It allows the body to adjust to the light and dark cycle. Disruptions to the circadian rhythm are important risk factors for many diseases, including neurodegenerative illnesses. The central clock is controlled by the clock genes in the suprachiasmatic nucleus (SCN) of the brain, and one of the main functions of the circadian clock is to regulate lipid metabolism. There has been a lack of investigation on the circadian regulation of lipid metabolism-related apolipoprotein genes in the brain; thus, this study sought to summarize the rhythmic expression of clock genes and lipid metabolism-related apolipoprotein genes within the SCN of Mus musculus. Out of the 20 apolipoprotein genes that were studied by the published database, all 9 genes were highly expressed in the SCN. Most of the 6 genes showed rhythmic expression in the brain of mice, suggesting that the master clock might regulate them. The results, therefore, reveal a potential target for preventing and treating circadian disorders. We summarized most studies of lipid-related apolipoprotein genes within limited locations of the SCN and brain to further understand how disordered cerebral lipid metabolism causes multiple brain diseases and disorders. We reviewed recent studies, determined the unexplored questions, and identified a potential direction for further research.

Adventurous play, defined as exciting, thrilling play where children are able to take age-appropriate risks has been associated with a wide range of positive outcomes. Despite this, it remains unclear what factors might aid or hinder schools in offering adventurous play opportu-nities. The purpose of this systematic review is to synthesise findings from qualitative studies on the perceived barriers and facilitators of adventurous play in schools. A total of nine studies were included in the final synthesis. The review used two synthesis strategies: a meta-aggregative syn-thesis and narrative synthesis. Findings were similar across the two syntheses, highlighting that key barriers and facilitators were: adults’ perceptions of children; adults’ attitudes and beliefs about adventurous play and concerns pertaining to health; and, safety and concerns about legis-lation. Based on the findings of the review, recommendations for policy and practice as provided to support adventurous play in schools.

Background: Granular cell tumor is a benign neurogenic tumor of the subcutaneous and submucosal area. The tongue is the most affected site of the oral cavity. The clinical presentation is non-specific and manifests as a submucosal nodule or mass. Because of its non-specific presentation, a definitive diagnosis an only be established after a histopathological examination and an immunohistochemical study to search for a neurogenic origin. Methods: We report the case of a 48-year-old man who was referred for the management of a nodular lesion on the tip of his tongue that had increased in size over the previous three months. Results: A complete surgical excision was performed for the histopathological exam, and an immunohistochemical study confirmed a strong expression of S100 and CD68. A diagnosis of granular cell tumor was confirmed. There was no recurrence et three years follow-up. Conclusion: the GCT is a rare tumor of nervous origin of the oral mucosa, it is non-specific in expression, with a good prognosis after complete excision. the histological and immunohistochemical diagnosis of the lesion is essential for the diagnosis.

Phenol is added to acetophenone (methyl phenyl ketone) and to six of its halogenated derivatives in a supersonic jet expansion to determine the hydrogen bonding preference of the cold and isolated 1:1 complexes by linear infrared spectroscopy. Halogenation is found to have a pronounced effect on the docking site in this intermolecular ketone balance experiment. The spectra unambiguously decide between competing variants of phenyl group stacking due to their differences in hydrogen bond strength. Structures where the phenyl group interaction strongly distorts the hydrogen bond are more difficult to quantify in the experiment. For unsubstituted acetophenone, phenol clearly prefers the methyl side despite a predicted sub-kJ/mol advantage which is nearly independent of zero point vibrational energy, turning this complex into a challenging benchmark system for electronic structure methods which include long range dispersion interactions in some way.

Background: Exclusive enteral nutrition (EEN) is the recommended first-line induction therapy for pediatric patients with active luminal Crohn’s disease (CD). The primary aim of this retrospective study was to ascertain the efficacy of EEN used as induction therapy for children with newly di-agnosed CD resident in the South Island of NZ over a ten-year period (2010 – 2021). Secondary aims were to assess the clinical impact of EEN therapy on anthropometry, biochemistry, the pro-gression to medical therapies over three time periods, and to identify positive predictors of re-sponse to EEN therapy. Methods: This retrospective clinical case review collected data from children diagnosed with CD at Christchurch Hospital, Christchurch, New Zealand, and prescribed EEN as induction therapy between the years January 1st, 2010 – December 31st, 2021. Descriptive statistics, Spearman’s correlation coefficient, multivariate logistic regression test and standard t-tests were used for analyses. Results: Data were collected for total of 161 children, 128 (80%) children were offered EEN as induction therapy and were included in this analysis. One hundred and twenty-one (94.5%) children successfully completed an eight-week course of EEN, and a de-crease in PCDAI scores ≥ 15 points from baseline to the end of week 8 of EEN treatment was seen in 119 (98.3%). L1 and L4 disease location were positive predictors of response (p

The influence of distant London dispersion forces on the docking preference of alcohols of different size between the two lone electron pairs of the carbonyl group in pinacolone is explored by infrared spectroscopy of the OH stretching fundamental in supersonic jet expansions of 1:1 solvate complexes. Experimentally, no pronounced tendency of the alcohol to switch from the methyl to the bulkier tert-butyl side with increasing size is found. In all cases, methyl docking dominates by at least a factor of two, whereas DFT-optimized structures suggest a very close balance for the larger alcohols, once corrected by CCSD(T) relative electronic energies. Together with inconsistencies when switching from a C4 to a C5 alcohol, this points at deficiencies of the investigated B3LYP and in particular TPSS functionals even after dispersion correction, which cannot be blamed on zero point energy effects. The search for density functionals which describe the harmonic frequency shift, the structural change and the energy difference between the docking isomers of larger alcohols to unsymmetric ketones in a satisfactory way is open.

Functional somatic disorders (FSD) characterized by persistent and disabling physical symptoms are common in adolescents. Diagnostic uncertainty and insufficient illness explanations are proposed perpetuating factors that may constitute barriers for treatment engagement. This study evaluates the impact of manualized assessment and psychoeducation on diagnostic certainty and various clinical outcomes in adolescents with multi-system FSD. Ninety-one adolescents (15-19 years) included in a randomized trial testing group-based therapy (AHEAD) received systematic assessment (4 hrs.) and a subsequent psychiatric consultation (1.5 hrs.). Clinical outcomes included self-reported physical health, symptom severity, illness perception, illness related behavior, and psychological flexibility assessed before and approximately two months after assessment, prior to specialized treatment. Data were analyzed using t-tests. Immediately following assessment 71 (80.7%) adolescents out of 88 reported a higher diagnostic certainty and 74 (84.1%) reported that attending assessment gave them positive expectations for future treatment. A clinically relevant improvement of physical health was not observed at two months but considerable reductions were seen on symptom severity, illness worry, negative illness perceptions, limiting illness behavior and psychological inflexibility. The results underpin the importance of systematic assessment and psychoeducation which may be effective in their own right in specialized treatment of adolescents with severe FSD.

Pre-implantation horse conceptuses require nutrients and signals from histotroph, the composition of which is regulated by luteal progesterone and conceptus-secreted factors. To distinguish progesterone and conceptus effects we shortened the period of endometrial progesterone-priming by asynchronous embryo transfer. Day 8 embryos were transferred to synchronous (day 8) or asynchronous (day 3) recipients, and RNA sequencing was performed on endometrium and conceptuses recovered 6 and 11 days later (embryo days 14 and 19). Asynchrony resulted in many more differentially expressed genes (DEGs) in conceptus membranes (3473) than endometrium (715). Gene ontology analysis identified upregulation in biological processes related to organogenesis and preventing apoptosis in synchronous conceptuses on day 14, and in cell adhesion and migration on day 19. Asynchrony also resulted in large numbers of DEGs related to ‘extracellular exosome’. In endometrium, genes involved in immunity, the inflammatory response, and apoptosis regulation were upregulated during synchronous pregnancy and, again, many genes related to extracellular exosome were differentially expressed. Interestingly, only 14 genes were differentially expressed in endometrium recovered 6 days after synchronous versus 11 days after asynchronous transfer (day 14 recipient in both). Among these, KNG1 and IGFBP3 were consistently up-regulated in synchronous endometrium. Furthermore bradykinin, an active peptide cleaved from KNG1, stimulated prostaglandin release by cultured trophectoderm cells. The horse conceptus thus responds to a negatively asynchronous uterus by extensively adjusting its transcriptome, whereas the endometrial transcriptome is modified only subtly by a more advanced conceptus.

Introduction:The concept of same-day discharge has garnered increasing significance within orthopedic surgery, particularly in hip and knee procedures. Despite initial concerns surrounding the absence of prolonged hospital care, a burgeoning body of evidence highlights numerous advantages associated with same-day discharge, ranging from mitigating in-hospital infections to offering substantial financial and psychosocial benefits for both patients and healthcare providers. In this study, we aim to scrutinize the trends in same-day discharge specifically within the realm of total hip arthroplasties. Method:This retrospective analysis delves into the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database spanning from 2016 to 2021. Result:In this study, same-day hip patients skewed younger, comprising 48.3%females compared to 55.6% in hospitalized hip patients. Operatively, same-day hip surgeries boasted shorter durations, averaging 83.9 minutes, in contrast to the 92.3minutes for hospitalized hip procedures. Postoperatively, same-day hip patients exhibited significantly diminished rates of 30-day readmissions (1.7%vs. 3.5%), procedure-related readmissions (1.0%vs.2.1%), reoperations (1.1%vs.1.9%), and mortality (0.02% vs. 0.04%). In addition, we found that that unplanned readmissions in the same-day group are significantly predicted by being over 65 years old (OR: 2.0), having hypertension (OR: 1.6), chronic steroid usage (OR: 2.2), and severe COPD (OR: 2.0), while gender, emergent surgery indication, and smoking were not significant predictors. Moreover, the prevalence of the same-day discharge concept experienced a remarkable ascent from 2016 to 2021, with rates escalating from 1.5% to 25.6% of all total hip arthroplasties over a span of just six years. Conclusion:In conclusion, same-day discharge is a feasible and safe option for selected THA patients, improving healthcare efficiency and patient satisfaction.

The recent availability of commercial platforms for behavioral analysis in zebrafish larvae based on video-tracking technologies has exponentially increased the number of studies analyzing different behaviors in this model organism to assess neurotoxicity. Among the most commonly used assays in zebrafish larvae are basal locomotor activity (BLA) and visual motor response (VMR). However, the effect of different intrinsic and extrinsic factors that can significantly alter the outcome of these assays is still not well understood. In this work we have analyzed in 143 larvae the influence of age (5-8 days post-fertilization), time of day (8:00, 10:00, 12:00, 14:00; 16:00, 18:00, and 20:00 h), and experiment (three experiments performed at different days) on BLA and VMR results (4,004 analyses for each behavior). Results from both behaviors were adjusted to a Random-Effects linear regression model using generalized least squares (GLS), including in the model the effect of the three variables, the second-way interactions between them and the three-way interaction. The results presented in this manuscript show a specific effect of all three intrinsic factors and their interactions on both behaviors, supporting the view that the most stable time period for performing these behavioral assays is from 10:00 am to 04:00 pm, with some differences depending on age of the larva and the behavioral test.

Introduction: In the recent years alternate day dosing has been recommended in iron deficieny treatment. The aim of this study is to compare the efficacy and side effects of oral iron treatments given daily 1x1, alternate day 1x1 and 2x1 alternate day dosing in iron deficieny anemia patients. Methods: A total of 52 patients with a diagnosis of iron deficiency anemia with serum ferritin level of 25 µg/L or less were included in this retrospective study. Statistical analyzes were done with SPSS V.25. Results: The patients included in our study were between the ages of 18-51. All of the patients included in the study were female. A statistically significant increase was found between 0-14 days(p<0.001), 14-28 days(p<0.001) and 0-28 days(p<0.001) hemoglobin values in all patients. There was no statistically significant difference between 0-14 days (p=0.397) and 0-28 days(p=0.310) ferritin values in all patients. A statistically significant difference was found between 14-28 days(p<0.001) ferritin values. When the rate of change of hemoglobin and ferritin values between the groups was compared and no statistically significant difference was observed between the groups. The rate of change of ferritin values for 14-28 days was significant (p=0.012). There was no significant difference in the frequency of symptoms in the 14th day and 28th day controls for each group (p>0.05). The incidence of metallic taste and bloating symptoms was found to be statistically significant in the third control in the group with 2x1 drug use alternate day (p=0.094). Discussion: The only difference in efficacy was observed in ferritin values between 14th and 28th days. The increase in ferritin values was higher in the group that used 1x1 oral iron every day. However, since no difference was observed between the groups in terms of ferritin and hemoglobin values on days 0 and 28, all three groups were considered equally efficient. Side effects were mainly gastrointestinal side effects. Since the group that received 2x1 oral treatment alternate day had a statistically significantly higher rate of side effects, the patients’ treatment tolerance will be lower compared to the other groups. In conlusion, there is no difference in efficacy and side effects between the patient groups receiving 1x1 daily and 1x1 alternate day oral iron therapy, so 1x1 use alternate day is the most appropriate treatment method for oral iron therapy in terms of patient tolerance, adherence to treatment and pharmacoeconomics.

Purpose: A number of imaging readout schemes have been proposed for renal arterial spin labelling (ASL) to quantify kidney cortex perfusion, including gradient echo based methods of balanced fast field echo (bFFE) and gradient-echo echo-planar imaging (GE-EPI), or spin echo based schemes of spin-echo echo planar imaging (SE-EPI) and turbo spin-echo (TSE). Here, we compare these imaging schemes to evaluate the optimal imaging scheme for pulsed ASL (PASL) assessment of human kidney cortex perfusion at 3 T. Methods: Ten healthy volunteers with normal renal function were scanned using each 2D multislice imaging scheme, in combination with a respiratory triggered FAIR (flow-sensitive alternating inversion recovery) ASL scheme on a 3 T Philips Achieva scanner. All volunteers returned for a second identical scan session within two weeks of the first scan session. Comparisons were made between the imaging schemes in terms of perfusion weighted image (PWI) signal-to-noise ratio (SNR) and perfusion quantification, temporal SNR (tSNR), spatial coverage, and repeatability. Results: For each imaging scheme, renal cortex perfusion was calculated (bFFE: 276 ± 29 mL/100 g/min, GE-EPI: 222 ± 18 mL/100 g/min, SE-EPI: 201 ± 36 mL/100 g/min, TSE: 200 ± 20 mL/100 g/min). Perfusion was found to be higher for GE based readouts compared to SE based readouts, with significantly higher measured perfusion for the bFFE readout compared to all other schemes (P < 0.05), attributed to the greater vascular signal present. Despite the PWI-SNR being significantly lower for SE-EPI compared to all other schemes (P < 0.05), the SE-EPI readout gave the highest tSNR and was found to be the most reproducible scheme for the assessment of kidney cortex, with a CoV of 17.2%, whilst minimizing variability of the perfusion weighted signal across slices for whole kidney perfusion assessment. Conclusion: For the assessment of kidney cortex perfusion, SE-EPI provides optimal tSNR, minimal variability across slices and repeatable data acquired in a short scan time with low specific absorption rate.

During the 90 days following hospitalization for acute heart failure, ejection fraction and type of discharge medications have been shown in clinical trials to have little effect on mortality. We examined the recent literature addressing brain-related etiologies of sudden death following heart failure. Two mechanisms of sudden unexpected death have been suggested to possibly result from 4 significant influences on pathophysiology in the brain. The two causes of death are severe cardiac arrhythmia, and neurogenic pulmonary edema. They are both mediated through the brainstem autonomic nuclei generally, and executed specifically through the dorsal motor nucleus of the vagus nerve. The four significant influences on pathophysiology in the brainstem autonomic nuclei are: 1) Hyper-stimulation of neurons in the solitary tract nucleus, increasing their metabolic requirements; 2) Inadequate blood flow at a vascular watershed terminus; 3) Additionally decreased blood flow following vasoconstriction related to relative hyperventilation and decreased pCO2 levels; 4) Gravitational ischemia in the brain—caused by the weight of the brain mass sitting above the brainstem. Changes in head tilt release gravitational ischemia in the brain. There is no specific head position (relative to gravity) that is considered favorable or unfavorable for an extended period of time (i.e. more than 24 hours). Even a small degree of head elevation, used in managing pulmonary congestion, may increase gravitational ischemia in the posterior fossa and brainstem. In this paper we suggest a new and important research avenue for intervening in cardiac arrhythmias, and preventing their occurrence, through the non-invasive use of head-tilting, and other head repositioning maneuvers. This could potentially help many geriatric patients with heart failure, who have decreased mobility in bed, and who tend to stay in one position longer, thereby increasing gravitational ischemia in the brain.

Digital dentistry, including CAD/CAM dentistry, is perhaps the most disruptive innovation in dentistry to date. The rapid development of digital dentistry technologies over the past several decades has enabled clinicians to improve patient care by significantly reducing the time necessary for the restorative phase of treatment. Advancements in intra-oral scanning and computer-aided design and manufacturing (CAD/CAM), in conjunction with new dental CAD/CAM ceramic materials, have simplified patient care and made same-day dentistry a reality. This review aims to present the most recent advancements described in current literature as well as to document the successful implementation of digital dentistry into a predoctoral program. The overall process of CAD/CAM same-day dentistry and the accompanying advancements in software and materials were presented and discussed. Implementation of technology and personnel requirements were reviewed. CAD/CAM dentistry has been influential in shaping and improving dental practice and education, and this influence will only continue with time.

Colours were ubiquitous in the medieval world, and castles were no exception. While in the eyes of most people their rich colour schemes manifested power and wealth, some could also read the more nuanced messages these colours conveyed. The main objective of this paper is to discuss the use and role of colour in the interiors of castles of medieval Bohemia and Poland. The picture is complemented by the analysis of colour decorations of defensive residences of the Teutonic Order, for which colour schemes of external facades can be addressed as well. The dis-cussion takes into account the varying state of preservation and draws from the available writ-ten accounts. To present the most complete picture possible, we discuss royal residences, for which unfortunately limited data is available, as well as better-preserved castles of dukes and knights. We discuss the identified iconographic programmes and their chivalric, heraldic, and hagiographic motifs. Also within the scope of our discussion are late forms of floral decorations, known as “green chambers”. The numerous examples presented in the paper prove that colour was an important tool of visual social communication in castle architecture: it complemented the symbolism, and sometimes carried an independent message.

In this work, the Pumped Storage Unit (PSU) is proposed to be integrated with wind-thermal generation system owned by a company whose aim is to maximize its profit through optimal self-scheduling of its units by finding the best bidding strategy in day-ahead energy market. The mathematical formulation of the scenario based unit-commitment and coordinated trading problem is formulated as a stochastic mixed integer linear program. The formulation takes into account several uncertain parameters; such as the wind power generation, energy market prices, and imbalances up/down prices. The expected total profit obtained from energy trading with and without coordinating pumped storage system (PSS) with thermal-wind generation system were compared, and a significant improvement in profit resulted from coordination was observed. Furthermore, coordination between PSS and wind-thermal generation improve the conditional value at risk (CVaR) which monitors the biding risk level.

To explore the expression characteristics and biological functions of related genes of medicago terrestris under long day conditions, and to lay a foundation for revealing the molecular mechanism of medicago terrestris under long day conditions. The leaves of 'R108' tribulus Medicago sativa at branch stage (A), bud stage (B), initial flowering stage (C) and full flowering stage (D) were sequenced by RNA-Seq technology. The genome of Medicago sativa, a related species of Tribulus tribulus, was used as a reference genome for sequence comparison. The transcriptomes of three adjacent periods (A vs B, B vs C, C vs D) were analyzed for differentially expressed genes and photoperiod related differentially expressed genes were screened. A total of 6875 differentially expressed genes were detected. GO functional analysis showed that differentially expressed genes were mainly involved in biological processes, cell components and molecular functions, among which the most differentially expressed genes were involved in cell components. KEGG enrichment analysis showed that differentially expressed genes were mainly involved in circadian rhythm, photosynthesis - antenna protein, ribosome metabolism and other pathways. The number of single nucleotide variants detected by cSNP analysis was 312875, and the frequency of A/G and C/T were the highest. The function of eggNOG was divided into 23 categories, with a total of 26745 genes having similarities, 9008 genes were classified as function unknown, 2669 genes were classified as signal transduction mechanism, 2194 genes were classified as transcription, etc. In different developmental stages (A vs B, B vs C, C vs D), 3463 up-regulated and 3412 down-regulated differentially expressed genes were found. The difference between up-regulated and down-regulated genes was the most obvious between bud stage and initial flowering stage. In addition, a total of 79 flowering genes were found, of which 51 differential genes were screened out to participate in photoperiodic regulation pathway, 23 differential genes were up-regulated, and 28 differential genes were down-regulated. The ratio of gene-LOC11410562(GI), gene-LOC11435974(CO), gene-LOC11422615(TOC1) and gene-LOC11432385(LHY) was higher than that of gene-LOC25500742(PHYA) and gene-LOC11 431402(ELF3), gene-LOC11434778(Col13), gene-LOC25498015(Col6), and gene-LOC11415514(Col9) were preexpressed. The above differentially expressed genes were significantly expressed in different development stages of Terrestris alfalfa, which laid a foundation for further study of the molecular mechanism of Terrestris alfalfa.

Strawberry is produced in tropical regions using imported cultivars adapted to temperate and subtropical climates. These cultivars, under tropical conditions, produce below their genetic potential. Through multivariate analyses, the objective was to evaluate and select short-day strawberry genotypes based on intraspecific crosses, product characteristics, and fruit quality. The genotypes were obtained from the cross between 'Camino Real' (female parent) and the first-generation genotypes RVCA16, RVCS44, RVFS06, RVFS07, and RVDA11 (male parent), obtained in previous selections. The experimental design consisted of augmented blocks with standard controls, consisting of first-generation genotypes and commercial cultivars. The fruits were harvested and evaluated for productivity and post-harvest characteristics: Total Fruit Mass (MTF); Total Number of Fruits (TFN); Average Fruit Mass (AFM); Commercial Fruit Mass (CFM); Fruit Commercial Number (CFN); Average Commercial Mass of Fruits (ACFM); Total Soluble Solids (TSS); Firmness (F); Brightness (L); Hue Angle (°Hue); Chroma (C). The selection index of Mulamba and Mock (1978) was used with an intensity of 3% to obtain superior genotypes and submitted to multivariate analysis for comparative purposes. Of the 1500 genotypes evaluated, it was possible to select 44 genotypes with characteristics superior to the 13 controls. The RVDA11CR59 genotype showed better values for the attributes of interest, but the RVCS44CR population, from the cross between 'Camino Real' × RVCS44 ('Camarosa' × 'Sweet Charlie'), obtained the highest number (16) of individuals among those selected. Significant traits had high heritability but were not necessarily reflected in high selection gain. Coefficients of genetic variation were high, indicating sufficient genetic variability to select genotypes for these traits. When multivariate analyses were used, it was possible to group the selected genotypes into the same cluster according to the similarity and balance in the responses to the evaluated variables, demonstrating that these analyses help other parameters choose superior genotypes. The multivariate analysis allowed the selection of more balanced genotypes for production and post-harvest traits for tropical climates.

Cows produce saliva in very large quantities to lubricate and facilitate food processing. Estimates indicate an amount of 50-150 liter per day. Human saliva has previously been found to contain numerous antibacterial components, such as lysozyme, histatins, members of the S-100 family and lactoferrin to limit pathogen colonization. Cows are dependent of a complex microbial community in their digestive system for food digestion. We wondered how this would influence the content of their saliva. We therefore sampled saliva from five humans and both nose secretions and saliva from six cows and separated the saliva on SDS-PAGE gradient gels and analyzed the major protein bands by LC-MS/MS. The cow saliva was found to be dominated by a few major proteins only, the carbonic anhydrase 6, a pH stabilizing enzyme, and the short palate, lung and nasal epithelium carcinoma-associated protein 2A (SPLUNC2A), also named bovine salivary protein 30kDa (BSP30). This latter protein has been proposed to play a role in local antibacterial response by binding bacterial lipopolysaccharide (LPS) and inhibit bacterial growth, but may instead according to more recent data instead have primarily surfactant activity. Numerous peptide fragments of mucin-5B were also detected in the MS analysis. However, mucins stain poorly by the gel staining solution and they are large and have difficult to enter regular gels why their presence easily are overseen. Interestingly, no major band on gel was detected representing any of the antibacterial proteins indicating that cows may produce them at very low levels not to harm the microbial flora of their digestive system. The nose secretions of the cows primarily contained the odorant protein, a protein thought to be involved in enhancing the sensing of smell by the olfactory receptors to enhance the possibility to quickly sense potential poisonous food components. High levels of secretory IgA was also found in one sample of cow mouth drippings indicating a strong upregulation during an infection. The human saliva we more complex containing both secretory IgA, amylase, carbonic anhydrase 6, lysozyme, histatins and a number of other less abundant proteins.

Zika virus (ZIKV) is a notable arbovirus with maternal, sexual, and TORCH-related transmission capabilities. After 2015, Brazil had the highest number of ZIVK-infected pregnant women who lost their babies or delivered them with Congenital ZIKV Syndrome (CZS). ZIKV infection has been linked to variations in endogenous retroviruses (ERVs) and interleukins within the placenta. ERVs, remnants of ancient viral infections integrated into the genome, include syncytin receptors crucial for placental development. Interleukins, immune response regulators, aid immune tolerance and support syncytial structure development in the placenta, where syncytin receptors facilitate vital cell-to-cell fusion events. Since ZIKV can infect trophoblast cells, we investigated the relationship between ZIKV infections and ERV and interleukin modulations. Investigating the impact of ZIKV on trophoblast cells, we examined two cell types (BeWo and HTR8) infected with ZIKV-MR766 (African) and ZIKV-IEC-Paraíba (Asia-Brazilian) using Taqman and RT2 Profiler PCR Array assays. While early ZIKV infection (24-48 hours) did not induce differential ERV and interleukin expression, future studies involving additional trophoblastic cell lineages and extended infection timelines will illuminate the dynamic interplay between ZIKV, HERVs, interleukins, and cytokines essential for placental formation and function.

Background: Quality of life (QoL) in IC/BPS patients is an evidence gap in guidelines, because studies are limited and outdated. Therefore, guidelines might not reflect the current situation accurately, and no possible improvements in QoL of these patients. Secondly, guidelines suggest multimodal approach in therapy, however unknown is how the efficacy of these therapies are perceived by the patient themselves. The aim of this study is to investigate the perception of IC/BPS patients on their QoL and to determine which treatments they received and how they evaluate the efficacy of these various (alternative) therapies.Methods: Quantitative retrospective database study in IC/BPS patients, compiled of existing patient survey data (n=217) from July 2021. Results: The QoL of patients is affected significantly by IC/BPS. This is evident from the substantial self-reported impact by patients, the various affected domains on EQ-5D 5L. The QoL was not negatively affected by delayed diagnosis, but there were differences between female and males. Secondly, there was the wide array of (alternative) treatments utilized, although some have doubtful results and high dropout rates. Conclusion: QoL is considerably impaired in IC/BPS patients. Coagulation therapy and intravesical GAG therapy were most appreciated treatments. The diverse responses and adherence to various treatments warrant a personalized approach (phenotype-oriented therapy). To achieve improvement in the QoL, it is important to incorporate the patient’s perspective in treatment guidelines.

This study explores the impact of the ‘pre-intervention effects’ of a community-based interventions. This refers to participatory research processes and parallel publicity in the media on changes in alcohol use and relevant mechanisms (rules and norms about alcohol, accessibility of alcohol in a formal setting) among adolescents before any intervention is implemented. In a quasi-experimental study, adolescent data were collected twice by means of self-report among adolescents living in two municipalities (control and experimental condition). Regression analysis showed pre-intervention main effects on adolescents’ perceived accessibility of alcohol in a formal setting. Moreover, among adolescents aged 15 years and older, the normative decline in strictness of rules and norms was less steep in the experimental condition compared to the control condition. Also, adolescents aged 14 years and younger in the experimental condition reported more weekly drinking compared to their peers in the control condition. No differential effects across gender were found. To conclude, applying a co-creational approach in the development of an intervention, not only contributes to more effective interventions in the end, but involvement of and discussions in the community at the start of intervention planning are contributing to changes in targeted factors. This implies that public discussions about the development of intervention strategies should be considered as an essential feature of co-creation in community-based interventions.

The archival Rossi X-ray Timing Explorer (RXTE) Proportional Counter Array (PCA) observations of HZ Her/Her X-1 are analyzed here. The time periods for Anomalous Low States are refined. The 35-day X-ray lightcurve of Her X-1 is produced using 35-day phases determined with RXTE All-Sky Monitor (ASM) and Swift Burst Altert Telescope (BAT) data, with adjustments based on the RXTE/PCA data. The result is the highest sensitivity 35-day lightcurve of Her X-1. The RXTE/PCA data were separated into 8 differents states of the 35-day cycle: Main High (MH) turn-on, MH, MH decline, Low State (LS) 1, Short High (SH) turn-on, SH, SH decline, and LS2. Orbital lightcurves were created for each state, and the different states are compared. Eclipse data was extracted for each state to determine the changes of eclipse shape with 35-day phase. A scattering corona model was fit to the eclipses for the different 35-day states: this shows that the corona is present at all 35-day phases with similar intensity. We carried out a search for previously-reported dips with no absorption, but did not find any.

Safely resuming sporting events while the coronavirus is spreading is challenging – yet possible – if the science is taken into account. Two main ways the coronavirus can spread among football players is through air-suspended microdroplets (and possibly aerosols), and via contact with contaminated surfaces. Here we estimated virus survival in dried saliva droplets on a football pitch (i.e., on the grass) and on the ball itself, and compared these measures between mid-day and nighttime matches. We find, based on experiments with the enveloped phage Phi6 – a surrogate for SARS-Cov-2 – that while the virus survives reasonably well on both pitch and ball during a nighttime match (~10% survival), virtually no viruses survived the 90-minute duration of a mid-day match on a hot, sunny day. These results, taken together with studies reporting rapid deactivation of coronavirus in aerosols by sunlight, suggest that playing football in mid-day reduces the likelihood of transmission between players, and thus increases players’ safety.

In California, an average of 41,900 patients are diagnosed annually with Staphylococcus bacterial infection; out of these, 24,090 patients have methicillin-resistant Staphylococcus aureus (MRSA) infection and 17,810 patients have methicillin-sensitive Staphylococcus aureus (MSSA) infection. The aim of this paper is to find out whether there is a significant difference in strain dominancy and in what direction. The paper gathered and analyzed data for period of five years of infection rate due to Staphylococcus aureus. This study indicates that a significant difference in dominancy exists, the MRSA infection rate (an average of five years period) is 1.35 times higher than the MSSA infection rate (P-value < 0.05, CI: 95%), but the gap between the two infection rates is decreasing. The infection rate of both MRSA and MSSA is in a path of decline.

The operation of electricity and natural gas transmission networks in the U.S. are increasingly interdependent, due to the growing number of installations of gas fired generators and the penetration of renewable energy sources. This development suggests the need for closer communication and coordination between gas and power transmission system operators in order to improve the efficiency and reliability of the combined energy system. In this paper, we present a co-simulation platform for examining the interdependence between natural gas and electricity transmission networks based on a direct current unit-commitment and economic dispatch model for the power system and a transient hydraulic gas model for the gas system. We analyze the value of day-ahead coordination of power and natural gas network operations and show the importance of considering gas system constraints when analyzing power systems operation with high penetration of gas generators and renewable energy sources. Results show that day-ahead coordination contributes to a reduction in curtailed gas during high stress periods (e.g., large gas offtake ramps) and a reduction in energy consumption of gas compressor stations.

Oryzias latipes is an important model organism for physiology, genetics and developmental studies, and has also emerged a relevant vertebrate model for aquatic ecotoxicology. Knowledge regarding its associ-ated microbiota on the other hand is still scarce and limited to adults, despite the relevance of associated microbiome to hosts biology. This study provides first insights into the establishment of bacterial mi-crobiota during early developmental stages of laboratory-reared medaka using a 16SrRNA sequenc-ing-based approach. Major shifts in community compositions are observed, from a Proteobacte-ria-dominated community in larvae and juveniles to a more phylum diverse community towards adult-hood, with no obvious difference between female and male specimens. Major bacterial taxa found in adults, including genera Cetobacterium and ZOR0006, establish progressively and are rare during early stages. Dominance shifts are comparable to those documented in another major model teleost, the zebrafish. Results from this study provide a basis for future work investigating the influence of meda-ka-associated bacteria during host development.

In this review, we provide an overview of the current knowledge on the different sexual systems and sex determining mechanisms in bivalves, with a focus on the various epigenetic and genetic factors that may be involved. The final section of the review provides recent discoveries on sex-specific mitochondrial genes in bivalves possessing the unconventional system of doubly uniparental inheritance of mitochondria (which is found in several members of the orders Mytiloida, Unionoida, Veneroida and Nuculanoida). The genes involved in this developmental pathway could represent the first sex determination system in animals in which mitochondrially-encoded genes are directly involved.

Obesity is a significant public health concern with higher morbidity. Obesity patients are at risk of severe COVID-19 infection and obesity is a higher risk factor for intensive Care Unit admission in COVID-19 infection. Obesity status affects lung volumes, cardiac structure and hemodynamics. Obesity is associated with a low inflammation state, endothelial dysfunction, hyperinsulinaemia and metabolic disorders. The authors review cardio-respiratory pathophysiological aspects involved in obesity and propose clinical management in obese patients infected by COVD-19.

Wildfires can be destructive to highway infrastructure. Despite the substantial number of wildfires experienced every year, research on the physical impacts of wildfire on highways has been understudied. This research examines historical and potential future highway physical damage from wildfires. To accomplish our research objectives, we examined three major areas related to physical harm to highways and the consequences of that damage – physical characteristics, roadway impacts, and traffic impacts. These categories were subsequently broken into additional metrics, the first being physical characteristics, which includes length of highway affected and reduced average daily traffic (RADT) impacts during the event. Roadway impacts were broken into the number of trees requiring removal (those that present a danger either standing or fallen), pavement damage (burning asphalt concrete), slope/rock scaling (loose hazard rocks/vegetation), and structural damage (guardrail, signs, and delineators). Traffic impacts included the need for traffic control, road closures required, and reduced annual average daily traffic (RAADT) impacts for the year. The physical characteristics on the three highways researched during the 2020 Oregon Labor Day wildfires (Beachie Creek, Archie Creek, and Holiday Farm) indicated less than 61% of the highways were affected. The highway impacts, which included damage from hazard trees, damage to various structures – guardrail, signs, and delineators as well as bridges, slope/rock scaling damage and pavement destruction – averaged 34% for the three highways, while the three of eight arterial highway routes studied in the Oregon Cascades saw a 21% reduction in AADT. Results from this study can be used not only to assess physical damage to highways from wildfires, but as a baseline for measuring and assessing potential future wildfire highway impacts.

Three cases of Day-Night Band (DNB) observations of the Visible Infrared Imaging Radiometer Suite (VIIRS) onboard the Suomi National Polar-orbiting Partnership (SNPP) are explored for applications to assess the ocean environment and monitor ocean dynamics. An approach to use the DNB radiance ratio was developed in order to better continuously assess the ocean diurnal and short-term environmental changes with VIIRS DNB observations. In the La Plata River Estuary, the sediment fronts showed 20–25 km diurnal inshore-offshore movements on March 13, 2017. In the waters off the Argentina coast in the South Atlantic, VIIRS DNB measurements provided continuous observations and monitoring of the algae bloom development and migration between 24–26 March 2016. This algae bloom generally kept the same spatial patterns, but moved nearly 20 km eastward in the three-day period. In the Yangtze River Estuary and Hangzhou Bay region in China’s east coast, VIIRS DNB observations also revealed the complicated coastal dynamic changes between 12–14 April 2017. Even though there are still some challenges and limitations for monitoring the ocean environment with VIIRS DNB observations, this study shows that satellite DNB observations can provide additional data sources for ocean observations, especially observations during the nighttime.

Background: The UK dairy sheep industry is relatively small but growing, particularly for cheese and yogurt products. Anecdotally, sheep milk (SM) is better tolerated by humans than cows’ milk and could have environmental as well as health benefits. All milk contains sub-micron particles called extracellular vesicles (EV) which are mainly derived from the mammary epithelium. Physiologically, milk derived EV are thought to aid development of infant immunity and the microbiome but may also have health benefits to adult humans. Methods: Using sequential ultracentrifugation vesicles of &lt;1µm (LEV) followed by &lt;200nm (sEV) were isolated from six individual sheep during mid lactation. RNA was extracted and microRNA analysed by RTqPCR for sequences previously identified in cows’ milk. Human THP-1 monocytes were differentiated into macrophages and incubated with SM-derived LEV and sEV in the presence of pro-inflammatory LPS to measure effects on secretion of the chemokine CCL-2 or in the presence of DMNQ and fluorescent dihydrorhodamine-1,2,3 to measure reactive oxygen species. Results: LEV induced an increase in ROS in both monocytes and macrophages, whilst sEV decreased DMNQ-mediated ROS in macrophages but not monocytes. Interestingly, the LEV did not induce CCL2 release, however they increased LPS-induced CCL2 secretion in monocytes but not macrophages. miR26a, miR92a, miR125b, miR155, miR223, were identified in both sEV and LEV by RT-qPCR and could be responsible for modulation of ROS and CCL2 expression. Conclusions: These findings suggest that sheep milk can influence human monocyte/macrophage responses and so is worthy of further investigation for its potential human and non-human animal health benefits.

The athletic performance and safety of racehorses is influenced by hoof-surface interactions. This intervention study assessed the effect of eight horseshoe-surface combinations on hoof acceleration patterns at impact and foot-off in 14 galloping Thoroughbred racehorses retired from racing. Aluminium, barefoot, GluShu (aluminium-rubber composite) and steel shoeing conditions were trialled on turf and artificial (Martin Collins Activ-Track) surfaces. Shod conditions were applied across all four hooves. Tri-axial accelerometers (SlamStickX, range ±500 g, sampling rate 5000 Hz) were attached to the dorsal hoof wall (x: medio-lateral, medial=positive; y: along dorsal hoof wall, proximal=positive; z: perpendicular to hoof wall, dorsal=positive). Linear mixed models assessed whether surface, shoeing condition or stride time influenced maximum (most positive) or minimum (most negative) accelerations in x, y and z directions, using ≥40,691 strides (significance at p&lt;0.05). Day and horse-rider pair were included as random factors and stride time as a covariate. Collective mean accelerations across x, y and z axes were 22–98 g at impact and 17–89 g at foot-off. Mean stride time was 0.48 ± 0.07 s (mean ± 2 s.d.). Impact accelerations were larger on turf in all directions for forelimbs and hindlimbs (p≤0.015), with the exception of forelimb z-minimum, and in absolute terms maximum values were typically double minimum values. Surface-type affected all foot-off accelerations (p≤0.022), with the exception of hindlimb x-maximum; for example, there was an average increase of 17% in z-maximum across limbs on the artificial track. Shoe-type influenced all impact and foot-off accelerations in forelimb and hindlimb datasets (p≤0.024), with the exception of hindlimb impact y-maximum. Barefoot hooves generally experienced the lowest accelerations. Stride time affected all impact and foot-off accelerations (p<0.001). Identifying factors influencing hoof vibrations on landing and hoof motion during propulsion bears implication for injury risk and racing outcomes.

Understanding the effect of horseshoe-surface combinations on hoof kinematics at gallop is relevant for optimising performance and minimising injury in racehorse-jockey dyads. This intervention study assessed hoof breakover duration in Thoroughbred ex-racehorses from the British Racing School galloping on turf and artificial tracks in four shoeing conditions: barefoot, aluminium-rubber composite (GluShu), aluminium and steel. Shoe-surface combinations were tested in a randomized order and horse-rider pairings (n=14) remained constant. High-speed video cameras (Sony DSC-RX100M5) filmed the hoof-ground interactions at 1000 frames per second. The time taken for a hoof marker wand fixed to the lateral hoof wall to rotate through an angle of 90 degrees during 384 breakover events was quantified using Tracker software. Data were collected for leading and non-leading front and hind limbs, at gallop speeds ranging from 23–56 km h-1. Linear mixed-models assessed whether speed, surface, shoeing condition or any interaction between these parameters (fixed factors) significantly affected breakover duration. Day and horse-rider pair were included as random factors and speed was included as a covariate. The significance threshold was set at p&lt;0.05. For all limbs, breakover times decreased as gallop speed increased (p&lt;0.0005), although a greater relative reduction in breakover duration for hindlimbs was apparent beyond approximately 45 km h-1. Breakover duration was longer on turf compared to the artificial surface (p≤0.04). In the non-leading hindlimb only, breakover duration was affected by shoeing condition (p=0.025) and an interaction between shoeing condition and speed (p=0.023). Future work seeks to relate these results to hoof accelerometer data.

The origin and climate impact of Arctic aerosols, like the Arctic Haze, are not fully understood. Therefore, long-term aerosol observations in the Arctic are performed. In this study we present a homogenised data set from sun and star photometer operated in the European Arctic, in Ny-Ålesund, Svalbard, from 2004 – 2023. Due to polar day and polar night it is crucial to use observations of both instruments. Their data is evaluated in the same way and follows the cloud-screening procedure of AERONET. Additionally, an improved method for the calibration of the star photometer is presented. We found out, that winter months are generally more polluted and have larger particles than summer. While the monthly median Aerosol Optical Depth (AOD) decreases in spring, the AOD increases significantly in autumn months. The Arctic Haze is not characterised by large particles and can not be distinguished from large aerosols in winter months. With autocorrelation analysis we found out, that AOD events usually occur with duration of several hours and are therefore caused by large-scale processes and may have a periodicity of several days. Local processes can be neglected in Ny-Ålesund but long-range transport plays a major role for the Arctic aerosol budget. We also compared AOD events with large-scale processes, like large-scale oscillation patterns, sea ice, weather conditions or wildfires on the Northern Hemisphere but did not find one single cause, which clearly determines the Arctic AOD.

Epithelial barrier damage plays a central role in the development and maintenance of allergic inflammation. The rise in airways epithelial barrier permeability alters the tissue homeostasis and allows the allergen and other external agents penetration. Different factors contribute to barrier impairment, such as eosinophilic infiltrate and allergens proteases action: the eosinophilic cationic proteins and the allergens' proteolytic activity have a central role in contributing to epithelial damage. In the airways, the allergens proteases degrade the epithelial junctional proteins allowing the allergen penetration and the uptake by dendritic cells. The increase in allergen-immune system interactions induce the release of the alarmins and the activation of type 2 inflammatory pathways causing, or worsening, the main symptoms at skin, bowel and respiratory levels. We aim to highlight the molecular mechanisms underlying allergenic proteases-induced epithelial barrier damage and the role of immune response in allergic asthma onset, maintenance and progression. We further will explore clinical and radiological potential biomarkers of airways remodeling in allergic asthma patients.

Background Natural Saccharomyces cerevisiae yeast strains exhibit very large genotypic and phe-notypic diversity. Breeding programs taking advantage of this characteristic, are widely used for yeast selection in the wine industry, especially in the recent years when winemakers need to adapt their production to climate change. The aim of this work was to evaluate a Marker Assisted Se-lection (MAS) program to improve malic acid consumption capacity of Saccharomyces cerevisiae in grape juice. Methods Optimal individuals of two unrelated F1-hybrids were crossed to get a new genetic background carrying many “malic consumer” loci. Then, eleven QTLs already identified were used for implementing the MAS breeding program. Results By this way, extreme individuals able to consume more than 70% of malic acid in grape juice were selected. These individuals were tested in different enological matrixes and compared to their original parental strains. They greatly reduced the malic acid content at the end of alcoholic fermentations, they appeared to be robust to the environment and accelerate the ongoing of malo-lactic fermentations by Oenococcus oeni. Conclusions This study illustrates how MAS can be efficiently used for selecting industrial Saccharomyces cerevisiae strains with outlier properties for winemaking.

SORL1 gene encodes LR11/SorLA, a protein that binds -amyloid precursor protein (bAPP) and drives its intracellular trafficking. SORL1 mutations occurring frequently in a subset of familial cases of Alzheimer’s disease (AD) have been documented but their pathogenic potential is not yet clear and questions remain concerning their putative influence on the physiopathological processing of bAPP. We have assessed the influence of three SORL1 mutations that were described as likely disease-causing and that were associated with either benign (SorLA924) or severe (SorLA141 and SorLA511) AD phenotypes. We examined the influence of wild-type and mutants SorLA in transiently transfected HEK293 cells expressing either wild-type or Swedish mutated bAPP on bAPP expression, secreted Ab and sAPPa levels, intracellular Ab40 and Ab42 peptides, APP-CTFs (C99 and C83) expressions, a-, b- and g-secretases expressions and activities as well as Ab and CTFs-degrading enzymes. These paradigms were studied in control conditions or after pharmacological proteasomal modulation. We also established stably transfected CHO cells expressing wild-type SorLA and established the colocalization of wild-type SorLA and bAPP. Overall, although we mostly confirmed previous data concerning the influence of wild-type SorLA on bAPP processing, we were unable to evidence significant alterations triggered by our set of SorLA mutants, whatever the cells or pharmacological conditions examined. Our study however does not rule out the possibility that other AD-linked SORL1 mutations could indeed affect bAPP processing and that pathogenic mutations examined in the present study could interfere with other cellular pathways/triggers in AD.

Background and Aims: Screening and assessment of cognitive changes in adults with Intellectual Disabilities, mainly Down Syndrome (DS), is crucial to offer appropriate services to their needs. We present a systematic review of the existing instruments assessing dementia, aiming to support researchers and clinicians’ best practice. Methods: Searches were carried out in the databases Web of Science; PubMed; PsycINFO in March 2019 and updated in May 2020. Studies were selected and examined if they: (1) focused on assessing age-related cognitive changes in person with ID; (2) included adults and/or older adults; (3) included scales and batteries for cognitive assessment. Results: Forty-eight cross-sectional studies and twenty-six longitudinal studies were selected representing a total sample of 5,851 participants (4,089 DS and 1,801 with other ID). In those studies, we found 38 scales, questionnaires, and inventories, and 14 batteries for assessing cognitive and behavioural changes in adults with DS and other ID. Conclusion: The most used instrument completed by an informant or carer was the Dementia Questionnaire for Learning Disabilities (DLD), and its previous versions. We discuss the strengths and limitations of the instruments and outline recommendations for future use.

Cryptosporidiosis is a common illness in young cattle that causes high morbidity and some mortality. A common prophylactic treatment are halofuginone products but it seems likely disease could be reduced by other other pharmacological products or some management strategies. We undertook a systematic review and meta-analyses on key outcomes for treatment of calves before and after 5 days of age with any management strategy, any nutritional strategy or any non-halofuginone product. A systematic literature search was undertaken with data extracted for outcomes = oocyst shedding, diarrhea, mortality and weight gain. Experiments had to describe results for same age animals in contemporary arms. Control animals had to be observed concurrently in planned experiments (pre-post and case-control studies were not eligible). Both randomized and other clinically controlled trials were eligible. Results were subgrouped by study design and outcomes were described in detail where at least two articles described the same treatment strategy. 55 articles were found. Significantly lower incidence of oocyst shedding, diarrhea burden and mortality was reported in many experimental arms, especially when animals started treatment before 5 days old. Weight gain was not mostly affected by treatment, however, by three weeks of age. The evidence base is at least encouraging but insufficient about paromomycin, bumped kinase inhibitors and azithromycin treatment, especially for diarrhea and oocyst shedding, given late or early. Azithromycin is the most promising of these.

In many regions where drinking water supply is intermittent and unreliable, households adapt by storing water in cisterns or rooftop tanks. Both intermittent supply and stored water can be vulnerable to contamination by microorganisms with deleterious health effects. The Guadalajara Metropolitan Area is a rapidly growing urban center with over five million residents where household storage is nearly ubiquitous. This pilot study was conducted in July 2018 to examine the microbiological quality of drinking water in Guadalajara. Samples were tested for free available chlorine residual, total coliform bacteria, and E. coli. A survey on access to water and public perspectives was also conducted. Water exiting rooftop tanks exceeded regulatory limits for total coliform levels in half of the homes studied. Piped water arriving at two homes had total coliform levels that far exceeded regulatory limits. No E. coli were detected in any of the samples. Only 35% of homes had a chlorine residual between the recommended 0.2 and 1.5 mg/L. Many homes reported unpleasant odors and colors. Only 7% of residents drank the piped water. Future studies are needed, especially during April and May when many homes reported a higher disruption to water service.

The ability to identify and rank risk is essential for efficient and effective supervision of financial service firms, such as banks and insurers. Risk ranking ensures limited resources are allocated where they are most needed. Today, automatic risk identification within insurance supervision primarily relies on quantitative metrics based on numerical data (e.g. returns). The purpose of this work is to assess whether Natural Language Processing (NLP) and cognitive networks can achieve similar automated risk ranking and identification by analysing textual data, i.e. NIDT=829 investor transcripts from Bloomberg. To this aim, this work explores and tunes 3 NLP techniques: (1) keyword extraction enhanced by cognitive network analysis; (2) valence/sentiment analysis; and (3) topic modelling. Results highlight that keyword analysis, enriched by term frequency-inverse document frequency scores and semantic framing through cognitive networks, could detect events of relevance for the insurance system like cyber-attacks or the COVID-19 pandemic. Cognitive networks were found to highlight events that related to specific financial transitions: The semantic frame of "climate" grew in size by +538% between 2018 and 2020 and outlined an increased awareness that agents and insurers expressed towards climate change. A lexicon-based sentiment analysis achieved a Pearson’s correlation of ρ=0.16 (p&lt;0.001,N=829) between sentiment levels and daily share prices. Although relatively weak, this finding indicates that insurance jargon is insightful to support risk supervision. Topic modelling is considered less amenable to support supervision, because of a lack of results’ stability and an intrinsic difficulty to interpret risk patterns. We discuss how these automatic methods could complement existing supervisory tools in automated risk ranking.

Staphylococcus aureus and coagulase-negative staphylococci account for about 80% of infections associated with medical devices and are associated with increased virulence due to their ability to form biofilm. In this study, we aimed to construct a comprehensive reference map followed by significant pathway analysis in the proteome of S. aureus biofilm grown for 3-days as compared with 24 h planktonic using a high-resolution TMT based MS. We identified proteins associated with secondary metabolites, ABC transporters, biosynthesis of amino acids, response to stress, and amino sugar and nucleotide sugar metabolism were significantly upregulated in the 3-day biofilm. In contrast, proteins associated with virulence factors, microbial metabolism in diverse environments, translation, and energy metabolism were significantly downregulated. GO functional annotation indicated that more proteins are involved in metabolic processes, catalytic activity, and binding in biofilm, respectively. Among the significantly dysregulated proteins, hyaluronidase (hysA) in conjunction with chitinase may play a significant role in the elimination and/or prevention of biofilm development. This study advances the current S. aureus subproteomes, identified potential pathways significant to biofilm biology and helped to understand their potential role in S. aureus which may shed light on developing new therapeutic regimes including antibiofilm agents in the treatment of biofilm-infections related with implantable medical devices.

There has been a rise in the prevalence of atopic dermatitis (AD) globally especially in low-and middle-income countries such as Nigeria. The condition has been linked to genetic predisposes, living conditions, and environmental factors. Environmental factors are considered a significant contributor to AD in low- and middle-income countries. This study determined the prevalence of AD in southwestern Nigeria and identified risk factors in home and school environments that children aged 6 to 14 years are exposed to. A cross-sectional study was adopted, and the total sample size was 349. Four randomly selected health facilities were used for the study. A questionnaire was used to determine the risk factors in the population. Data analysis was done using the latest version of Statistical Package for Social Science (SPSS). The prevalence of atopic dermatitis in this study is 25%. Atopic dermatitis was found to be common in females ( 27%). Children who lived where trucks pass on the street almost daily had the highest cases of atopic dermatitis (28%). Children with rugs in their houses and those whose houses are surrounded by bushes also had higher cases of atopic dermatitis at 26% and 26% respectively. Children who played on school grass, attended creche with rubber toys, and attended a school where wooden chairs and chalkboards were used had higher numbers of AD cases at 26%, 26%, 28%, and 27% respectively. This study identified home and school exposure that predisposes children to AD. It is envisaged that the study will serve as a basis for possible research on evidence-based treatment options.

It is urgent to find new antibiotic classes to replenish the empty development pipeline of antibiotics. Recently, pyrrolobenzodiazepines (PBDs) with a C8-linked aliphatic-heterocycle have been identified as a new broad spectrum antibiotic class with activity against Gram-negative bacteria. The active imine moiety of the reported lead pyrrolobenzodiazepine compounds was replaced with amide to obtain the non-DNA binding and non-cytotoxic dilactam analogues to further understand the structure activity relationship and improve the safety potential of this class. The synthesized compounds were tested against panels of multidrug resistant Gram-positive and Gram-negative bacteria, including WHO priority pathogens. Minimum inhibitory concentrations for the dilactam analogues ranged from 4 – 32 mg/L for MDR Gram-positive bacteria, compared to 0.03 to 2 mg/L for the corresponding imine analogues while they were found to be inactive against MDR Gram-negative bacteria, with an MIC &gt;32 mg/L, compared to an MIC of 0.5 to 32 mg/L. A molecular modelling study suggests the lack of imine functionality also affects the interaction of PBDs with DNA gyrase. This study suggests the presence of N10-C11 imine moiety is crucial for broad spectrum activity of pyrrolobenzodiazepines.

Over the past decade, Thailand has experienced a rapid increase in its elderly population. Many unfavorable health outcomes among elderly people are associated with nutrition. Nutrition in elderly people is affected by physical, mental, and social factors. This study explored the food choices and dietary practices among community-dwelling elderly people in Thailand from the perspective of both caregivers and the elderly people themselves. Six focus group discussions and six semi-structured interviews were conducted in the Samut Sakhon Province of Thailand. A combination of deductive and inductive thematic analyses was adopted, and the results show that physical and mental factors and societal factors are important determinants of food choices. Moreover, a changing food environment and economic factors were found to affect food choices. Issues of trust in food safety and food markets were highlighted as growing issues. Therefore, fostering healthy food choice interventions that consider both environmental and societal aspects is necessary.

This case study features an observation of an obese female (body mass index ≥ 30 kgm-2) who undertook a 10-day water and electrolyte fast with the aim of reducing body fat and improving physiological markers of health. A comprehensive range of physiological measures (body mass, girths, blood pressure, body fluid balance, urine osmolarity, and resting oxygen consumption), mood indicators, metabolic markers (blood ketones, blood glucose, breath ketones, urine ketones), and measurement of intake and expenditure (fluid intake, food intake, nutritional macros, steps taken, and estimated movement caloric expenditure) were measured before, during and after the fasting period to determine the effectiveness of undertaking extended therapeutic fasting for improving markers of health and weight loss. Body mass on the first day of the fast was 95.1 kg and on the tenth and final day of the fast it was 88.1 kg representing a loss of 7 kg at a rate of 0.7 kg·day1. Mean body mass in the 15 days after the fast was 88.3 ± 0.4 kg. This case study is novel in reporting key physiological and psychological markers over a 10-day fast, and in pre- and post-fast periods. A 10-day fast appears to be a safe and effective method of weight loss, mood is positively affected by fasting and weight loss from fasting can be sustained providing care is taken in the approach to post-fasting nutrition.

We transformed the existing learning program Language Shower, which is used in some Norwegian day-care centers in the Grorud district of Oslo municipality, into a digital solution using an app for smartphone or tablet with the option for further enhancement of presentation by a NAO robot. The solution was tested in several iterations and multiple day-care centers over several weeks. Measurements of the children’s progress across learning sessions indicate a positive impact of the program using a robot as compared to the program without robot. In-situ observations and interviews with day care center staff confirmed the solution’s many advantages, but also revealed some important areas for improvement. In particular, the speech recognition needs to be more flexible and robust, and special measures have to be in place to handle children speaking simultaneously.

Based on hospital capacities, facts from past experience with the coronavirus disease 2019 (COVID-19) virus and the number of dark infections during the second wave (DII = 2D2), a reasonable limiting value of 140/D2 for the 7-day incidence per 100,000 persons (MSDIHT) and a second wave herd immunization threshold fraction value of 0.26 in Germany were calculated. If the MSDIHT is held below this limiting value, the German hospital system can cope with the number of new seriously infected persons without any triage decisions. On the basis of the SIRV epidemics model, the classical threshold values for herd immunization were calculated for 18 countries. For these countries, the dates regarding when herd immunization against the second COVID-19 wave will be reached were estimated

The intake of omega-3 polyunsaturated fatty acids (PUFA) of the average consumer is generally low and products like fish oils high in omega-3 PUFA have become a popular dietary supplement. There is a need for more sources of omega-3 PUFA to cover the increasing demand. This study investigated whether livers from different lean fish species could be a potential new source of oils rich in omega-3 PUFA. The seasonal variation in lipid content, fatty acid composition, peroxide value and free fatty acid content of livers from cod, hake, ling, coalfish and monkfish was determined and the effect of storage conditions on the fishing vessel (ice vs frozen) was studied. Generally, the lipid content and composition of the livers from the five fish species varied similarly during the two years of sampling period with significantly lower values in spring (March, April) and higher values in fall (November, October). Storage conditions were found to have no significant effect on the quality and oil composition. Monkfish livers were less suitable for production of omega-3 oil due to their lower lipid and EPA content and higher FFA levels. Coalfish had higher fluctuations in oil composition during sampling period, which potentially makes a standardised quality difficult to obtain. Cod, hake and ling were the most suitable species for fish liver oil production.

Background. Transferrin receptor 1 (TfR1), glucose transporter 1 (GLUT1), and CD98hc are candidates for targeted therapy at the blood-brain barrier (BBB). Our objective was to challenge the expression of TfR1, GLUT1, and CD98hc in brain capillaries by the histone deacetylase inhibitor (HDACi) valproic acid (VPA). Methods. Primary mouse brain capillary endothelial cells (BCECs) and brain capillaries isolated from mice injected intraperitoneally with VPA were examined using RT-qPCR and ELISA. Targeting to the BBB was performed by injecting monoclonal anti-TfR1 (Ri7217)-conjugated gold nanoparticles measured using ICP-MS. Results. In BCECs co-cultured with glial cells, Tfrc mRNA expression was significantly higher after 6 h VPA returning to baseline after 24 h. In vivo Glut1 mRNA expression was significantly higher in males, but not females', receiving VPA, whereas Cd98hc mRNA expression was unaffected by VPA. TfR1 increased significantly in vivo after VPA, whereas GLUT1 and CD98hc were unchanged. Uptake of anti-TfR1-conjugated nanoparticles was unaltered by VPA in spite upregulated TfR expression. Conclusions. VPA upregulates TfR1 in brain endothelium in vivo and in vitro. VPA does not increase GLUT1 and CD98hc proteins. The increase in TfR1 does not result in higher anti-TfR1 antibody targetability, suggesting targeting sufficiently occurs with available transferrin receptors without further contribution from accessory VPA-induced TfR1.

The 26th June, 1917 tsunamigenic earthquake in Samoa is considered the largest historical event on record to have impacted this region in terms of earthquake magnitude and intensity. Yet, very little is known about the scale and distribution of tsunami impacts for this event compared with the recent 2009 tsunamigenic earthquake which originated in a proximal source region at the Northern Tonga Trench. In this paper, we reconstruct the 1917 tsunami from source to inundation using the BG-Flood numerical modelling suite to understand the magnitude of inundation for this event. Model outputs representing inundation extent and hazard depth intensities at spatially flexible grid resolution (10 m, 20 m and 40 m), are validated using available tide gauge records in Apia harbour and limited observations of runup that were derived from historical records. Results indicate variable modelled-to-observed consistency using available source models, wave and runup validation data. Significant discrepancies in recorded vs modelled wave arrival time at Apia of between 30—40 mins are observed, with modelled runup underestimated in southeast Upolu Island compared with the rest of the country where runup observations are available (e.g., west Savai’i Island). We combine the inundation model with available digital distributions of buildings and roads in the RiskScape multi-hazard risk analysis software, to produce exposure metrics for understanding the likely impacts on present-day coastal asset and population distributions if a similar tsunami were to occur. A comparison between the distribution of hazard risk exposure for the 1917 and 2009 events is discussed along with the uncertainties in our results, with suggestions for future work offered.

Pneumonia is the leading cause of hospitalization in pediatric patients. Disease severity greatly influences pneumonia progression and adverse health outcomes such as hospital readmission. Hospital readmissions have become a measure of healthcare quality to reduce excess expenditures. The aim of this study was to examine 30-day all-cause readmission rates and evaluate the association between pneumonia severity and readmission among pediatric pneumonia hospitalizations. Using 2018 Nationwide Readmissions Database (NRD), we conducted a cross-sectional study of pediatric hospitalizations for pneumonia. Pneumonia severity was defined by the presence of respiratory failure, sepsis, mechanical ventilation, dependence on long-term supplemental oxygen, and/or respiratory intubation. Outcomes of interest were 30-day all-cause readmission, length of stay, and cost. The rate of 30-day readmission for the total sample was 5.9%, 4.7% for non-severe pneumonia, and 8.7% for severe pneumonia (p&lt;0.01). Among those who were readmitted, hospitalizations for severe pneumonia had a longer length of stay (6.5 vs. 5.4 days, p&lt;0.01) and higher daily cost ($3,246 vs. $2,679, p&lt;0.01) than admissions for non-severe pneumonia. Factors associated with 30-day readmission were pneumonia severity, immunosuppressive conditions, length of stay, and hospital case volume. To reduce potentially preventable readmissions, clinical interventions to improve the disease course and hospital system interventions are necessary.

Racial and ethnic disparities exist in diabetes prevalence, health services utilization, and out-comes including disabling and life-threatening complications. Home health care may especially benefit older adults with diabetes through individualized education, advocacy, care coordina-tion, and psychosocial support for patients and their caregivers. This study examined factors as-sociated with hospital discharge to home health care and subsequent utilization of home health care among a cohort of Medicare beneficiaries with diabetes, age 50 and older, living in the United States. The cohort (n=786,758) was followed for 14 days after a diabetes-related index hospitalization, using linked Medicare administrative, claims, and assessment data (2014-2016). Multivariate logistic regression models included patient demographics, comorbidities, hospital length of stay, geographic region, neighborhood area deprivation, and rural/urban setting. In ful-ly adjusted models, hospital discharge to home health care was significantly less likely among Hispanic (OR 0.8, 95% CI 0.8-0.8) and American Indian (OR 0.8, CI 0.8-0.8) compared to white patients. Among those discharged to home health care, all racial/ethnic minority patients were less likely to receive services within 14-days. Further work should focus on eliminating systemic racism in home health care referral and systemic barriers to receiving home health care services.

Energy system optimization models (ESOM) are widely used to inform about energy transition strategies. The heterogeneity of consumers, especially in the heat sector, is rarely considered in these model types. Integrating consumer heterogeneity and behavioral factors into ESOMs may generate new insights for energy policy. In this study a literature review was conducted, identifying empirical data on consumer behavior for adopting residential heating systems. This data was integrated into an ESOM for the German heat sector, combining established methods for integrating consumer heterogeneity and a novel approach for calculating indirect costs, representing behavioral factors. The incorporation of consumer choice leads to a higher diversity in technology market shares in a business as usual and an ambitious measures scenario. Especially, the future role of log wood technologies in the private household sector may have been underestimated in previous studies and should be discussed, when designing policies. Still, these findings need to be handled with care, since the empirical data basis and the methodological basis is limited.