Fouling by activated sludge in membrane bioreactor (MBR) processes for wastewater treatment can be reduced using several strategies such as backflushing, relaxation, and chemical cleaning. Some proprietary systems such as Avanti’s RPU-185 Flexidisks MBR use novel circular rotating, flat sheet membranes to assist in limiting this fouling. An attempt has already been made to model this novel rotating fouling process by developing a simulation model based on first principles and traditional fouling mechanisms. In order to directly compare the potential benefits of rotational MBR system, a follow-up study was carried out using Avanti’s newly developed static (non-rotating) Flexidisks MBR system. This new process uses the same proprietary and patented membrane modular arrangement as used in the circular rotational unit, but is configured instead as a static square-shaped unit which is in-line with the more traditional and popular format used for submerged flat sheet MBR systems. During this study, the results from operating the static pilot unit were simulated and modelled using a standard fouling model coupled with a viscosity to mixed liquor relationship model. These results were then compared with those obtained from running the rotating MBR model however with rotational switching functions turned off and rotational parameters set to a static mode. This comparison was done to ascertain whether the basic premise of the developed rotational model was sound in empirical terms when compared to a standard MBR flux model. The study concluded that relatively good agreement was reached between the two types of models, thus vindicating the usage of a complex rotational MBR model. Follow on studies will now compare results from the rotating MBR system using rotational models developed by other researchers to ascertain the effectiveness rotating MBR modelling approach.

The fluorinated organic compounds have superior physicochemical properties than general organic compounds due to the strong C-F single bond, and widely used in medicine, biology, pesticides, and materials science. In order to gain a deeper understanding of the physicochemical properties of fluorinated organic compounds, fluorinated aromatic compounds have been investigated by various spectroscopic techniques. 2-Fluorobenzonitrile and 3-fluorobenzonitrile are important fine chemical intermediates, and their excited state S1 and cationic ground state D0 vibrational features remain unknown. In this paper, we used two-color resonance two photon ionization (2-color REMPI) and mass analyzed threshold ionization (MATI) spectroscopy to study S1 and D0 states vibrational features of 2-fluorobenzonitrile and 3-fluorobenzonitrile. The precise excitation energy (band origin) and adiabatic ionization energy were determined to be 36028 2 cm-1 and 78650 5 cm-1 for 2-fluorobenzonitrile; and 35989 2 cm-1 and 78873 5 cm-1 for 3-fluorobenzonitrile, respectively. The density functional theory (DFT) at the levels of RB3LYP/aug-cc-pvtz, TD-B3LYP/aug-cc-pvtz, and UB3LYP/aug-cc-pvtz were used to calculate the stable structures and vibrational frequencies for the ground states S0, excited state S1, and cationic ground state D0, respectively. Franck-Condon spectral simulations for transitions of S1 S0 and D0 S1 were performed based on above DFT calculations. The theoretical and experimental results are in good agreement. The observed vibrational features in S1 and D0 states are assigned according to the simulated spectra and the comparison with structurally similar molecules. Several experimental findings and molecular features were discussed in detail.

Futures markets are mainly used as a tool for price discovery and for risk management on the spot markets and enable diversification for international portfolio investments. With this study we aim (1) to investigate the causality relationship between futures markets and spot market and (2) to examine the causality relationship between futures markets and spot markets in different countries. We are interested in both the futures markets - spot market relations and the interactions between the markets at international level. For variables we used the the BIST30 spot index and BIST30 futures contract representing the Borsa Istanbul market and the Dow-Jones 30 index and Dow-Jones 30 futures contract, which are the most important indices representing the US markets. Daily closing price data for the period between 2nd January, 2009 and 18th June, 2018 were analyzed using correlation, unit root test, causality test and regression equations. The results of the study show that the futures markets continue their price discovery role for both the spot markets and futures markets and are influential on other futures and spot markets at international level. These findings are important for investors wanting to invest in Turkey and in similarly considered emerging market economies. It will help investors take informed decisions by providing them with a more efficient price estimations utilizing the futures markets.

A new model for international bed numbers is applied to local area populations for English Clinical Commissioning Groups (CCGs) where the Age Standardized Mortality Rate (ASMR) is used as a measure of population health and hence for total occupied hospital bed demand (elective plus emergency admission types, including acute, rehabilitation, mental health, and maternity), rather than simple bed availability. A 100-unit increase in ASMR (European Standard population) leads to a 15.3 – 30.7 (feasible range) unit increase in occupied beds per 1,000 deaths. ASMR shows why the Australian states of the Northern Territory and Tasmania have an intrinsic higher bed demand than the other states – although in both cases the bed planning methodologies failed to indicate this need and both states show a large bed deficit. Due to the high volatility in bed demand the average bed demand for 2019 was determined by a linear trend using data for 2014/15 to 2019/20 — as the pre-COVID-19 baseline. The slope of the relationship between occupied beds per 1,000 deaths and deaths per 1,000 population shows a power law function. As is to be expected there is scatter around the trend line which will partly arise from uncertainty in the expected occupied beds in 2019, fluctuations in both ASMR and deaths per 1,000 population from one year to another, changes in the number of persons on the elective, outpatient and diagnostic waiting lists, and local area variation in births and consequently upon maternity, neonatal and pediatric bed demand. Additional variation in bed demand will arise from differences in the level of funding for social care, especially elderly care, and to a lesser extent upon patients using private health care, and charitable hospices for palliative care. However, after including the change in bed demand arising from ASMR the model is sufficiently accurate to identify gross differences in bed demand as a prelude to further investigation. The model requires further extension to cover specialty-level demand, and perhaps segregation between elective and emergency types of inpatient demand. A method for benchmarking the whole hospital’s average bed occupancy is given which enables them to run at optimum efficiency and safety. Using this method English hospitals can be shown to operate at highly disruptive and unsafe levels of bed occupancy leading to deleterious ‘turn-away’. Turn-away implies bed unavailability for the next arriving patient. The problems associated with crafting effective bed planning are illustrated using the English NHS as an example.

(1) Background: To investigate the dynamic issues behind international variation in EWM. (2) A rolling EWM calculation is used to reveal seasonal changes in the EWM calculation and is especially relevant nearer to the equator. (3) Results: In addition to latitude country specific factors determine EWM. Females generally show higher EWM mainly due to respiratory conditions. The EWM for respiratory conditions in England and Wales ranges from 44% to 83% which is about double the all-cause mortality equivalent. Age has a profound effect on EWM with a peak in puberty and then increasing EWM at old age. The gap between male and female EWM seems to act as a diagnostic tool reflecting the infectious/metrological mix in each winter. Additional difference due to ethnicity are also observed. An EWM equivalent calculation for sickness absence demonstrates how additional health-related variables can be linked to EWM. (4) Conclusions: EWM does not reach a peak at the same time each year, especially so in the tropics. Countries midway between the equator and the poles show highest EWM. Differences between the genders are highly significant and seem to vary according to the mix of variables active each winter. Pandemic influenza does not elevate EWM, although seasonal influenza plays a part each winter.

Fleets of drones have attracted a lot of attention from the research community in recent years. One of the biggest challenges in deploying such systems is localization. While GNSS localization systems can only be effective in open outdoor environments, new solutions based on radio sensors (e.g., ultra-wideband) are increasingly being used for localization in various situations and environments. However, self-localization without prior knowledge of anchor positions remains an open problem which, for example, makes it impossible to track a moving target. In this article, we provide a comparison of different variants of gradient descent-based algorithms, with a new improved variant, for solving the localization problem using relative distance measurements and multilateration. It is applied to self-localization of anchors and tracking targets using ultra-wideband distance sensors. A realistic simulation of drone tracking and anchors’ localization is performed to demonstrate the robustness and accuracy of the proposed approach.

Background: As a result of the pandemic, families and children have faced physical, emotional, and mental challenges. However, there has been little attention given to the relationship between the COVID-19 pandemic and child development. This systematic review aims to identify the impact of the pandemic on child development, globally. Methods: This study follows the PRISMA guidelines for the systematic review of 16 quantitative and qualitative studies conducted between 2020-2023. Results: This systematic review suggest that the COVID-19 pandemic played a crucial role in hindering child development in early childhood. Conclusion: Therefore, it is important to promote and implement the use of policies and strategies to overcome these obstacles.

The surging electricity demand driven by a growing global population, coupled with the increasing electrification of industries, transportation, and power-intensive appliances, poses a substantial challenge to electricity systems worldwide. This challenge is further compounded by the pressing issue of climate change. To address climate change and mitigate the environmental consequences of fossil fuel use, renewable energy sources are expected to play a pivotal role. However, certain renewable sources, such as wind and solar, exhibit stochastic behavior, resulting in unpredictable power output and significant fluctuations. This intermittency presents a challenge in maintaining a stable and reliable power supply. To overcome this challenge and ensure a balanced electricity grid, the strategic deployment of energy storage devices throughout the power system becomes critically important. Energy storage technologies play a vital role in mitigating the mismatch between renewable power generation and consumption. Additionally, they enable the storage of surplus energy generated from renewable sources during periods of high production for later use during periods of low or no generation. Each technology possesses unique characteristics and applications, providing flexibility and diversity in energy storage solutions. This work provides an overview of different energy storage technologies and explores their role in establishing a sustainable power system.

Glufosinate, a glutamine synthetase (GS) inhibitor, often provides variable weed control depending on environmental conditions such as light, temperature and humidity at the time of application. Midday applications normally provide improved efficacy compared to applications at dawn or dusk. We investigated the physiological, molecular, and biochemical basis for the time-of-day effect on glufosinate efficacy in Amaranthus palmeri. GS1 and GS2 gene expression and protein abundance were assessed in different parts (young leaves, old leaves, and roots) of plants incubated in the dark compared to those in the light. The turnover of GS total activity was also evaluated overtime following glufosinate treatment at midday compared to dusk application. The results suggest that GS in A. palmeri is less expressed and less abundant in the dark compared to in the light. Midday application of glufosinate under intense light conditions in the hours following application provide full control of A. palmeri plants. Consequently, these plants are unable to recover GS activity by de novo protein synthesis. Full activity of GS is required for complete inhibition by the irreversible inhibitor glufosinate. Therefore, glufosinate applications should always be performed in the middle of the day when sunlight is intense, to prevent weed escapes from the herbicide treatment.

We construct a Bayesian estimator for the dilution of a wastewater sample. When wastewater is diluted by rainwater an estimate of the level of dilution is required if we are to normalise sample measurements of disease markers such as SARS-CoV-2 RNA. We consider the situation where flow measurements are available, but will regularly be unreliable because of the action of combined sewer outflows (CSOs) and wastewater storage tanks, which divert wastewater away from treatment plants when the flow is excessive. However, we also have proxies for the flow from various chemical markers (e.g.\ phosphate, ammonium, electrical conductivity), whose level per unit of population is fixed. The new flow estimator has multiple advantages compared to existing procedures: credible intervals for the estimates; optimal weighting of the chemical markers; systematic handling of missing and censored values; and model based smoothing without lags.

A proportion of osteoarthritis (OA) patients are unsatisfied with post-operative outcomes following total joint replacement surgery (TJR), with insufficient pain relief or poor functional improvement. Predicting those will have poor outcomes would be beneficial for patients and clinicians. The aim of this study was to determine the relationship between baseline anthropometric data and the concentration of pre-operative serum and peri-operative synovial fluid (SF) cytokines with 7-month post-operative outcomes in a cohort of knee and hip OA patients. 160 OA patients were recruited who were scheduled for TJR. The concentration of 24 cytokines were measured in blood and SF by multiplex assay. EQ5Dindex health status was assessed pre-operatively and at 7-months post-operatively. 13% of patients were identified as non-responders based on EQ5Dindex. Compared to responders, non-responders were of higher BMI, had greater waist and hip circumference and had higher levels of SF leptin but lower levels of SF Resistin (p<0.05). Linear regression analysis found a significant relationship between pre-operative body weight and post-operative response (ΔEQ5Dindex; r=0.222, p=0.049). The combination of body weight with SF amphiregulin and SF IL-6 provided an improved predictive model of post-operative response (r=0.470, p=0.035).

The emergence of the semiconductor industry in the early 1960s resulted in a significant stage in the evolution of computing when large computational problems, as typified by the application of the discrete Fourier transform (DFT) to the task of spectrum estimation, could suddenly, with the availability of suitable algorithms, be solved in close to real time fashion. This paper provides a brief and meandering account of the history of the DFT’s various solutions, referred to generically as the fast Fourier transform (FFT), the algorithm being chosen for its mathematical elegance, practical significance and ever‑increasing range of applications. We touch upon a few of the most striking personalities, places and events that were encountered along the way and look, in particular, at the recent British contribution to the journey.

Our aim is at three feels: i) study safe haven properties of sectoral CDS; ii) study hedging effectiveness and measure the diversification benefits of introducing them in both Conventional and Islamic stock markets portfolios and iii) compare these results with VSTOXX, Gold and Bitcoin indices. To do this, we estimate time varying hedge ratio using (A)DCC and GOGARCH models and then deduce hedging effectiveness.. We follow the same methodology for each sub-period and each refit to test the effect of bubble crypto currency and COVID-19 pandemic on hedging effectiveness. Empirical results show the superiority of industrial CDS sectoral index to hedge both conventional and Islamic stock markets whether long or short term despite that their performances were reduced slightly during the second and third periods. VSTOXX and Others sectoral CDS indices offers Hedging performances that are generally better than Bitcoin and gold.

"Metaverse" as a term came to the fore in 2021 when Facebook rebranded its corporate identity to Meta, and signaled its intention to invest at least $10 billion in developing the concepts and related products that year. However, there is still little consensus in defining what constitutes the metaverse, although there is a widespread, though not universal, agreement that it will bring a wide range of benefits across society. More specifically, the advent, and continuing evolution, of the metaverse has strategic and operational implications for, and impacts on, industry and business at large. Adopting an inductive, interpretivist approach, this exploratory research article presents case examples of the guidance on the responsible development of the metaverse provided by two IT business services companies. The article identifies the major risks and responsibilities associated with the metaverse and assesses how companies might address these responsibilities. Very little research has been published in this area and this article attempts to make a small contribution to filling this gap in the literature. The article finds that responsibilities are largely in line with those currently associated with corporate digital responsibility, and concludes that the strategic impact and extent of regulatory change will depend on the nature of the metaverse that materialises in the forthcoming decade.

All vaccines exhibit both specific and non-specific effects. The specific effects are measured by the efficacy against the target pathogen, while the non-specific effects can be detected by the change in all-cause mortality . All-cause mortality data (gender, age band, vaccination history, month of death) between January 2021 and May 2022 was compiled by the Office for National Statistics. COVID–19 vaccination gave good protection on many occasions but less so for younger ages. Each gender and age group shows its own unique vaccination benefit/disbenefit time profile. Individuals are free to make vaccination decisions. For example, women aged 18-39 show a cohort who do not progress beyond the first or second dose. The all-cause mortality outcomes for the Omicron variant showed a very poor response to vaccination with 70% of sex/age/vaccination stage/month combinations increasing all-cause mortality, probably due to unfavorable antigenic distance between the first-generation vaccines and this variant, and additional non-specific effects. The all-cause mortality outcomes of COVID–19 vaccination is far more nuanced than have been widely appreciated, and virus vector appear better than the mRNA vaccines in this specific respect. The latter are seemingly more likely to increase all-cause mortality especially in younger age groups. An extensive discussion/literature review is included to provide potential explanations for the observed unexpected vaccine effects.

We currently face several, interlinked environmental crises, including climate change, habitat destruction and biodiversity loss. However, many governments seem unwilling to take strong and immediate action to address these threats, preferring to promote neoliberal approaches to allow consumers and the general public to make environmentally friendly choices. This is despite neoliberal approaches being much less likely to be successful than government leadership, taxation, subsidies, and legislation in addressing environmental issues. In this study, we examine public perception of environmental threats and solutions to these threats, in a survey, mainly completed in the UK. Climate change is seen as the biggest issue, likely due to recent activist campaigns and subsequent media attention on the issue. Neoliberal attitudes, such as green consumer choices to environmental concerns, do still dominate in a series of possible presented solutions, and score more highly than lifestyle changes such as changing diet. However, when questioned specifically about plastic pollution, government intervention to ban all unnecessary plastic scored very strongly, indicating a shift from a consumer driven response. Furthermore, most participants think they are at best only partly ‘doing their bit’ to protect the environment. The results demonstrate that the public are aware that not enough is happening to protect the environment and provide evidence that there is willingness for stronger government intervention to address environmental issues, although there is potential resistance to major lifestyle changes.

Since 2020 COVID-19 has caused serious mortality around the world. Given the ambiguity in es-tablishing COVID-19 as the direct cause of death we first investigate the effects of age and sex upon all-cause mortality during 2020 and 2021 in England and Wales. Since infectious agents have their own unique age profile for death, we explore several methods to adjust single year of age deaths in England and Wales during 2019 (the pre-COVID-19 base year) to a pathogen-neutral single year of age baseline. This adjusted base year is then used to confirm the widely reported higher deaths in males for most ages above 43 years in both 2020 and 2021. During 2020 (+ COVID-19 but no vac-cination) both male and female population-adjusted deaths were significantly increased above age 35. A significant reduction in all-cause mortality among both males and females aged 75+ could be demonstrated in 2021 during widespread COVID–19 vaccination, however, below age 75 deaths progressively increased. This finding arises from a mix of vaccination and year of age profiles of deaths for the different SARS-CoV-2 variants. In addition, specific effects for age around puberty were demonstrated where females had higher deaths rather than males. There is evidence that year-of-birth cohorts may also be involved, indicating that immune priming to specific pathogen outbreaks in the past may lead to lower deaths for some birth cohorts. To specifically identify the age profile for the COVID-19 variants in 2020 to 2023, we employ the proportion of total deaths at each age which are potentially due to or ‘with’ COVID-19. The original Wuhan strain, and the Alpha variant show somewhat limited divergence in the age profile with the Alpha variant shifted to a moderately higher proportion of deaths below age 84. The Delta variant specifically targeted persons below age 65. The Omicron variants showed significantly lower proportion of overall mortality, with markedly higher relative proportion of deaths above age 65 steeply increasing with age to a maximum around 100 years of age. A similar age profile for the variants can be seen in the age-banded deaths in US states – although slightly obscured by using age bands rather than single year of age. However, the US data shows that higher male deaths are greatly dependent on age and the COVID-variant. Deaths determined as ‘due to’ COVID-19 (as opposed to ‘involving’ COVID-19) in England and Wales were especially over-estimated in 2021 relative to the change in all-cause mortality. This arose as a by-product of an increase in COVID-19 testing capacity in late 2020. Potential structure-function mechanisms for the year of age specificity of SARS-CoV-2 var-iants are discussed. The question is posed as to whether vaccines based on different variants carry the specific age profile through into the vaccine.

Based upon 30-years of research by the author a new approach to hospital bed planning and international benchmarking is proposed. The number of hospital beds per 1000 population is commonly used to compare international bed numbers. This method is flawed because it does not consider population age structure or the effect of nearness-to-death on hospital utilization. Deaths are also serving as a proxy for wider bed demand arising from undetected outbreaks of 3000 species of human pathogens. To remedy this problem a new approach to bed modelling has been developed which plots beds per 1000 deaths against deaths per 1000 population. Lines of equivalence can be drawn on the plot to delineate countries with higher or lower bed supply. This method is extended to attempt to define the optimum region for bed supply in an effective health care system. England is used as an example of a health system descending into operational chaos due to too few beds and manpower. The former Soviet bloc countries represent a health system overly dependent on hospital beds. Several countries also show evidence for over-utilization of hospital beds. The new method is used to define a potential range for bed supply and manpower where the current most effective health systems currently reside. The method is applied to total curative beds, medical beds, psychiatric beds, critical care, geriatric care, etc., and can also be used to compare different types of healthcare staff, i.e., nurses, physicians, surgeons. Issues surrounding the optimum hospital size and the optimum average occupancy will also be discussed. The role of poor policy in the English NHS is used to show how the NHS has been led into a bed crisis. The method is also extended beyond international benchmarking to illustrate how it can be applied at a local or regional level in the process of long-term bed planning. Issues regarding the volatility in hospital admissions are also addressed to explain the need for surge capacity and why an adequate average bed occupancy margin is required for an optimally functioning hospital.

The liver is a key node of whole-body nutrient and fuel metabolism and is also the principal site for detoxification of xenobiotic compounds. As such, hepatic metabolite concentrations and/or turnover rates inform the status of both hepatic and systemic metabolic diseases as well as the disposition of medications. As a tool to better understand liver metabolism in these settings, in vivo magnetic resonance spectroscopy (MRS) offers a non-invasive means of monitoring hepatic metabolic activity in real time both by direct observation of concentrations and dynamics of specific metabolites as well as by observation of their enrichment by stable isotope tracers. This review summarizes the applications and advances in human liver metabolic studies by in vivo MRS over the past 35 years and discusses future directions and opportunities that will be opened by the development of ultra-high field MR systems and by hyperpolarized stable isotope tracers.

In recent years, Web APIs have become a de facto standard for exchanging machine-readable data on the Web. Despite this success though, they often fail in making resource descriptions interoperable due to the fact that they rely on proprietary vocabularies that lack formal semantics. The Linked Data principles similarly seek the massive publication of data on the Web, yet with the specific goal of ensuring semantic interoperability. Given their complementary goals, it is commonly admitted that cross-fertilization could stem from the automatic combination of Linked Data and Web APIs. Towards this goal, in this paper we leverage the micro-service architectural principles to define a SPARQL Micro-Service architecture, aimed at querying Web APIs using SPARQL. A SPARQL micro-service is a lightweight SPARQL endpoint that provides access to a small, resource-centric, virtual graph. In this context, we argue that full SPARQL Query expressiveness can be supported efficiently without jeopardizing servers availability. Furthermore, we demonstrate how this architecture can be used to dynamically assign dereferenceable URIs to Web API resources that do not have URIs beforehand, thus literally ``bringing'' Web APIs into the Web of Data. We believe that the emergence of an ecosystem of SPARQL micro-services published by independent providers would enable Linked Data-based applications to easily glean pieces of data from a wealth of distributed, scalable and reliable services. We describe a working prototype implementation and we finally illustrate the use of SPARQL micro-services in the context of two real-life use cases related to the biodiversity domain, developed in collaboration with the French National Museum of Natural History.

A recent study has suggested that the age profiles for deaths due to COVID-19 variants differs between variants and shows male/female specificity. This study demonstrates the age and sex dependency is common among human pathogens. The often-reported higher susceptibility to infections among the young and elderly is true in general but does not apply to individual pathogens. Even among different types of pneumonia there are subtle differences in the age profile. The gender ratio between pathogens likewise shows wide variation from as low as 10% female admissions for leptospirosis to around 90% for gonococcal admissions. The observed age/sex variation observed for mortality due to COVID-19 variants is an expression of a far wider phenomenon with implications to the age/sex response to vaccines. We propose that such differences are likely to be controlled by small noncoding RNAs which act as potent regulators of gene expression leading to altered cell morphology, metabolism, immune function, and response to vaccines.

Abstract: Calcium-based catalysts are of a high interest for glycerol polymerization due to their high catalytic activity and large availability. However, their poor stability under reaction conditions is an issue. In the present study, we investigated the stability and catalytic activity of Ca-hydroxyapatites (HAps) as one of the most abundant Ca-source in nature. A stochiometric, a Ca-deficient and a Ca-rich HAps have been synthetized and tested as catalysts in the glycerol polymerization reaction. Deficient and stochiometric HAps exhibited a remarkable 100% selectivity to triglycerol at 15 % of glycerol conversion at 245 °C after 8 h of reaction in the presence 0.5 mol.% of catalyst. Moreover, under the same reaction conditions, Ca-rich HAp showed a high selectivity (88 %) to di- and triglycerol at a glycerol conversion of 27 %. Most importantly, these catalysts were unexpectedly stable towards leaching under the reaction conditions based on the ICP-OES results. However, based on the catalytic tests and characterization analysis performed by XRD, XPS, IR, TGA-DSC and ICP-OES, we found that HAps can be deactivated by the presence of the reaction products themselves, i.e., water and polymers.

Passive marine listening, involving the acoustic monitoring of underwater environments, has become increasingly vital for scientific research, environmental monitoring, and defense applications. However, the success of such applications critically depends on the ability to extract meaningful information from the often noisy and dynamic underwater acoustic environment. In this context, Mel-frequency cepstral coefficients (MFCCs) have emerged as an essential tool for feature extraction, capturing the spectral characteristics of marine sounds and making them ideal for species identification and sound event detection. This research presents an innovative approach to enhance the robustness of MFCC-based passive marine listening through adaptive noise reduction techniques. The proposed approach utilizes dynamic spectral subtraction to counter underwater noise, resulting in enhanced signal-to-noise ratios for desired sounds. This adaptive system adjusts to dynamic underwater noise, allowing it to concentrate on target sounds and suppress interference effectively. The experimentation further validates the effectiveness of the proposed approach, with results reaching 99% on the full dataset of 570 mammals and vessels, demonstrating the effectiveness of SVM and Random Forests in the classification of underwater audio.

All vaccines exhibit specific and nonspecific effects. Specific effects are shown by the efficacy against the target pathogen, while nonspecific effects can be detected by the change in all-cause mortality. The real-world non-COVID-19 all-cause mortality (NCACM) data for the population of England between January 2021 and May 2023 was assessed. All vaccines administered were based on the original Wuhan antigen. Each gender and age group, along with COVID-19 variant shows its own unique NCACM vaccination benefit/disbenefit time profile. The efficacy of COVID-19 vaccination against COVID-19 disease/death per se is undisputed, however, the nonspecific outcomes of COVID–19 vaccination is far more nuanced than have been widely appreciated. This confirms an earlier study on the unanticipated nonspecific effects of influenza vaccination against all-cause winter mortality. Interestingly, a high proportion of NCACM beneficial effects occurred during the first 21 days following COVID-19 vaccination, while the worst example of increased NCACM occurred during the fourth dose of COVID-19 vaccination in 19–40-year-olds for the interval >21 days post vaccination which led to NCACM 3- to 10-times higher than in the unvaccinated. By the time of the Omicron variant, NCACM outcomes in those aged 90+ are mostly adverse. The beneficial nonspecific effects of COVID-19 vaccination increase with age and reach their maximum effect during the second week post vaccination for age groups below 50 years, rising to during the third week for those aged 70+. Finally, we discuss the mechanisms by which COVID-19 vaccination could induce wider nonspecific effects. Most of these mechanisms seem to depend on gene regulation by noncoding RNAs which also interact with mRNAs. We suggest that further international studies are required to discern the nonspecific NCACM effects of the different COVID-19 variants other than the three variants prevalent in the UK, and different types/manufacturer of COVID-19 vaccines which have been employed around the world. We can only speculate regarding the nonspecific effects of the COVID-19 vaccines administered to persons with an asymptomatic infection, and during vaccine waning. Vaccines not only need to be effective against the target pathogen, as primarily determined by antibody production, but need to minimize any unanticipated adverse nonspecific effects against all-cause mortality.

The dynamics of suspended sediment involves inherent non-linearity and complexity as a result of the presence of both spatial variability of the basin characteristics and temporal climatic patterns. As a result of this complexity, the conventional sediment rating curve (SRC) and other empirical methods produce inaccurate predictions. Deep neural networks (DNNs) have emerged as one of the advanced modeling techniques capable of addressing inherent non-linearity in hydrological processes over the last few decades. DNN algorithms are used to perform predictive analysis and investigate the interdependencies among the most pivotal water quantity and quality parameters i.e., discharge, suspended sediment concentration (SSC), and turbidity. In this study, the Long short-term memory (LSTM) algorithm of DNNs is used to model the discharge-suspended sediment relationship for the Stony Clove Creek. The simulations were run using primary data on discharge, SSC and turbidity. For the development of the DNN models and examining the effects of input vectors, combinations of different input vectors (namely discharge, and SSC) for the current and previous days are considered. Furthermore, a suitable modelling approach with an appropriate model input structure is suggested based on model performance indices for the training and testing phases. The performance of developed models is assessed using statistical indices such as root mean square error (RMSE), mean absolute error (MAE), and coefficient of determination (R2). Statistically, the performance of DNN-based models in simulating the daily SSC performed well with observed sediment concentration series data. The study demonstrates the suitability of the DNN approach for simulation and estimation of daily SSC, opening up new research avenues for applying hybrid soft computing models in hydrology.

De novo regeneration of Cannabis sativa L. (cannabis) using tissue culture techniques remains unreliable and infrequent. Conventional methods for the regeneration and transformation of cannabis have not achieved the reliability and replicability needed to be integrated into research and breeding programs. Protoplast systems are effective for gene expression studies, transformation and genome editing technologies, and opens the possibility of somatic hybridization to create interspecific hybrids. To date, leaf-derived protoplast have been isolated for transient gene expression studies, but attempts at protoplast-to-plant regeneration have not been reported. The present study aims to test the efficacy of using a callus culture system, as an abundant source for protoplast isolation and lays the groundwork for a protoplast-to-plant regeneration system. Using hypocotyl-derived callus cultures, which are known to have relatively greater regenerative potential, the efficacy of protoplast isolation and initial cell division were assessed. In this study, the effect of 2-aminoindane-2-phosphonic acid (AIP) in callus culture media and the effect of subculture frequency on protoplast yield were assessed. This study found that inclusion of AIP at 1 mM resulted in a 334% increase in protoplast yield compared with AIP-free medium, representing the first known use of AIP in cannabis tissue culture. Inclusion of AIP led to a 28% decrease in total soluble phenolics and 52% decrease in tissue browning compared to the control medium. Lastly, a two-phase culture system for protoplast regeneration was tested. At a concentration of 2.0×10^5 protoplasts per mL, division was observed, providing the first know report of cell division from cannabis protoplasts and setting the stage for future development of a protoplast-to-plant regeneration system.

Obesity in the United States continues to worsen. Anthocyanin-rich fruits and vegetables provide a pragmatic dietary approach to slow its metabolic complications. Given American diet patterns, foods with high anthocyanin content could address dose-response challenges. In a placebo-controlled, randomized, crossover pilot study, determine the effect of 100% elderberry juice on measures of indirect calorimetry (IC), and insulin sensitivity/glucose tolerance. Overweight and obese adults were randomized to a 5-week study which included two 1-week periods of twice-daily elderberry juice (EBJ), or sugar-matched placebo consumption separated by a 3-week washout period. Following each 1-week test period, IC and insulin sensitivity/glucose tolerance was measured with a 3-hour meal tolerance test (MTT). Treatment differences were tested with linear mixed modeling. 22 prospective study volunteers (18F/4M) attended recruitment meetings, 10 volunteers completed the protocol, and 9 were analyzed for treatment differences. EBJ was well tolerated and compliance was 99.6%. Six IC measures (intervals) were created which coincided with 10-20 minute gaseous samplings in-between MTT blood samplings. Average CHO oxidation was significantly higher during the MTT after 1-week EBJ consumption (3.38 vs. 2.88 grams per interval, EBJ vs. placebo, p = 0.0113). Conversely, average fat oxidation was significantly higher during the MTT after 1-week placebo consumption (1.17 vs 1.47 grams per interval, EBJ vs. placebo, p = 0.0189). This was in-line with a significantly lower average respiratory quotient after placebo treatment (0.87 vs. 0.84, EBJ vs. placebo, p = 0.0114). Energy expenditure was not different. There was no difference in serum glucose or insulin response between treatments. This pilot study of free-living volunteers describes significant change in IC but not insulin sensitivity with an EBJ intervention. Controlled feeding and increased sample size will help determine the utility of EBJ on these outcomes.

As the digital era advances, many industries continue to expand their use of digital technologies to support company operations, notably at the customer interface, bringing new commercial opportunities and increased efficiencies. However, there are new sets of responsibilities associated with the deployment of these technologies, encompassed within the emerging concept of corporate digital responsibility (CDR), which to date has received little attention in the academic literature. This exploratory paper thus looks to make a small contribution to addressing this gap in the literature. The paper adopts a qualitative, inductive research method, employing an initial scoping literature review followed by two case studies. Based on the research findings, a simple model of CDR parameters is put forward, and the article concludes with a discussion of a number of emergent issues - fair and equitable access, personal and social well-being, environmental implications, and cross-supply chain complexities - that suggest possible directions for future research.

Windup, a progressive increase in spinal response to repetitive stimulations of nociceptive peripheral fibres, is a useful model to study central sensitization to pain. Windup is expressed by neurons in of both dorsal and ventral horn of the spinal cord. In juvenile rats, it has been demonstrated both in vivo and in vitro that windup depends on calcium-dependent intrinsic properties and their modulation by synaptic components. However, the involvement of these two components in the adult remain controversial. In the present study, by means of electromyographic and extracellular recordings, we show that windup in adult, in vivo, depends on a synaptic balance between excitatory NMDA receptors and inhibitory glycinergic receptors. We also demonstrate the involvement of L-type calcium channels in both the dorsal and ventral horn of the spinal cord. These results indicate that windup in adults is similar to juveniles rats and that windup properties are the same regardless spinal network, i.e. sensory or motor.

Smart materials represent an elegant class of (macro)-molecules endowed with the ability to react to chemical/physical changes in the environment. Herein, we prepared new photo responsive azobenzenes possessing halogen bond donor groups. The X-ray structures of two molecules highlight supramolecular organizations governed by unusual noncovalent bonds. In azo dye I-azo-NO2, the nitro group is engaged in orthogonal H···O···I halogen and hydrogen bonding, linking the units in parallel undulating chains. As far as compound I-azo-NH-MMA is concerned, a non-centrosymmetric pattern is formed due to a very rare I···π interaction involving the alkene group supplemented by hydrogen bonds. The Cambridge Structural Database contains only four structures showing the same I···CH₂=C contact. For all compounds, an ¹⁹F NMR spectroscopic analysis confirms the formation of halogen bonds in solution through a recognition process with chloride anion, and the reversible photo-responsiveness is demonstrated upon exposing a solution to UV light irradiation. Finally, the intermediate I-azo-NH2 also shows a pronounced color change due to pH variation. These azobenzenes are thereby attractive building blocks to design future multi-stimuli responsive materials for highly functional devices.

Proper species identification from ancient DNA samples is a difficult task that sheds light on the evolutionary history of pathogenic microorganisms. The field of palaeomicrobiology has undoubtedly benefited from the advent of untargeted metagenomic approaches that use next-generation sequencing methodologies. Nevertheless, assigning ancient DNA at the species level is a challenging process. Recently, the gut microbiome analysis of three pre-Columbian Andean mummies [1](Santiago-Rodriguez et al. 2016) has called into question the identification of Leishmania in South America. Here, the metagenomic data filed in MG-RAST (Metagenomics RAST server) were used for a further attempt to identify members of the Trypanosomatidae family infecting these ancient remains. For this purpose, we used two metagenomic analysis tools. In the first step, data were analysed using the ultrafast metagenomic sequence classifier, based on exact alignment of k-mers (Kraken). In the second step, we used Bowtie2, an ultrafast and memory-efficient tool for aligning sequencing reads to long reference sequences. We then compared the output results. These approaches highlight some interesting findings on potential infections by human pathogenic trypanosomatids in these three pre-Columbian mummies.

Keywords: conservation; cultural pluralism; environmental regulation; community-based natural resource management; Indigenous law

Trends in excess winter mortality (EWM) were investigated from the winter of 1900/01 to 2019/20. During the 1918-1919 Spanish flu epidemic a maximum EWM of 100% was observed in both Denmark and the USA. During the Spanish flu epidemic in the USA 70% of excess winter deaths were coded to influenza. EWM steadily declined from the Spanish flu peak to a minimum around the 1970’s to 1980’s. There is evidence that this decline was accompanied by a shift in deaths away from the winter, and that the EWM calculation shifted from a maximum around April to June in the early 1900’s to around March since 1967. EWM has a good correlation with the number of estimated influenza deaths, but in this context influenza pandemics after the Spanish flu only had an EWM equivalent to that for seasonal influenza. Using data from 1980 onward the effect of influenza vaccination on EWM was examined using a large international data set. No effect of increasing influenza vaccination could be discerned; however, there are multiple competing forces influencing EWM which will obscure any underlying trend, e.g., increasing age at death, multimorbidity, dementia, polypharmacy, diabetes, and obesity – all of which either interfere with vaccine effectiveness or are risk factors for influenza death. After adjusting the trend in EWM in the USA influenza vaccination can be seen to be masking higher winter deaths among a high morbidity US population. Winter deaths are clearly the outcome of a complex system of competing long-term trends.

The Ro60 autoantigen is an RNA-binding protein, and a core component of nucleocytoplasmic ribonucleoprotein (RNP) complexes. Ro60 is essential in RNA metabolism, cell stress response pathways, and cellular homeostasis. It stabilises and mediates quality control and cellular dis-tribution of YRNAs, retroelement transcripts, and misfolded RNAs. Ro60 transcriptional dysregulation or loss of function can result in the generation and release of RNA fragments from YRNAs and other small RNAs. Small RNA fragments can instigate an inflammatory cascade through endosomal TLRs and cytoplasmic RNA sensors, which typically sense patho-gen-associated molecular patterns (PAMPs) and mount the first line of defence against invading pathogens. However, recognition of host-originating RNA moieties from Ro60 RNP complexes can activate inflammatory response pathways and compromise self-tolerance. Autoreactive B cells may produce antibodies targeting extracellular Ro60 RNP complexes. Ro60 autoantibodies serve as diagnostic markers for various autoimmune diseases including Sjögren's disease (SjD) and systemic lupus erythematosus (SLE), and they may also act as predictive markers for an-ti-drug antibody response among rheumatic patients. Understanding Ro60’s structure, function, and role in self-tolerance can enhance our understanding of the underlying molecular mecha-nisms of autoimmune conditions.

Evaluating new, promising organic molecules to make next-generation organic optoelectronic devices necessitates the evaluation of charge carrier transport performance through the semi-conducting medium. In this work, we utilize quantum chemical calculations (QCC) and kinetic Monte Carlo (KMC) simulations to predict the zero-field hole mobilities of ~100 morphologies of the benchmark polymer poly(3-hexylthiophene), with varying simulation volume, structural order, and chain-length polydispersity. Morphologies with monodisperse chains were generated previously using an optimized molecular dynamics force-field and represent a spectrum of nanostructured order. We discover that a combined consideration of backbone clustering and system-wide disorder arising from side-chain conformations are correlated with hole mobility. Furthermore, we show that strongly interconnected thiophene backbones are required for efficient charge transport. This definitively shows the role "tie-chains" play in enabling mobile charges in P3HT. By marrying QCC and KMC over multiple length- and time-scales, we demonstrate that it is now possible to routinely probe the relationship between molecular nanostructure and device performance.

Family Integrated Care (FICare) is associated with improved developmental outcomes and decreased parental mental health risks in stable preterm infants. However, less is known about its application in critically ill infants who are at greater risk for adverse outcomes. The objective of this study was to assess the safety and feasibility of implementation of FICare in critically ill infants in the first few weeks of life. In this prospective cohort study, 41 critically ill infants were enrolled: 17 in observational group receiving standard care (SC)and 24 in the FICare Plus group. Resources were developed for staff and parents to support earlier engagement in infant care. Outcomes were assessed using standardized questionnaires. The t-test or Wilcoxon Rank-Sum test were used to compare continuous variables, while Chi-square or Fisher exact test were used for categorical variables, respectively. Baseline maternal and infant characteristics were similar in both groups. The tools and procedures developed for FICare Plus successfully supported greater engagement in the care of their infant with no increase in adverse events and no increase in parent stress. Preliminary measures of infant efficacy were similar in both groups. Total anxiety scores were high among all parents at enrolment {83.1 (67-94) vs 77.3 (66-86); p-value 0.4}. However, the scores prior to discharge were lower in FICare Plus group {78 (71-90) vs 63 (52-74.5); p-value 0.02}. This pilot study showed that it is feasible and safe to implement family integrated care in critically ill infants.

The UK food industry faces significant challenges to remain sustainable. With major challenges such as Brexit on the horizon, companies can no longer rely on a low labour cost workforce to maintain low production costs and achieve economic sustainability. Smart Systems (SS) is being seen as an approach towards achieving significant improvements in both economic and environmental sustainability. However, there is little evidence to indicate whether UK food companies are prepared for the implementation of such systems. The purpose of this research is to explore the applicability of Smart Systems in UK food manufacturing companies and, to identify the key priority areas and improvement levers for the implementation of such systems. A triangulated primary research approach is adopted and includes a questionnaire, follow up interviews and visits to thirty-two food manufacturing companies in the UK. The questionnaire and interviews are guided by the development of a unique measuring instrument created by the authors that is focusses upon SS technologies and systems. This paper makes an original contribution in that it is one of few academic studies to explore the implementation of SS in the industry and, provides a new perspective on the key drivers and inhibitors around its implementation. Findings suggest that the current turbulence in the industry could be bringing food companies closer to the adoption of such systems, hence it is a good time to define and develop the optimum SS implementation strategy.

Polyglycerols (PGs) are biocompatible and highly functional polyols with a wide range of applications, such as emulsifiers, stabilizers, antimicrobial agents, in many industries including cosmetics, food, plastic and biomedical. The demand increase for biobased PGs encourages researchers to develop new catalytic systems for glycerol polymerization. This review focuses on alkaline homogeneous and heterogeneous catalysts. The performances of the alkaline catalysts are compared in terms of conversion and selectivity, and their respective advantages and disadvantages are commented. While homogeneous catalysts exhibit a high catalytic activity, they cannot be recycled and reused, whereas solid catalysts can be partially recycled. The key issue for heterogenous catalytic systems, which is unsolved so far, is linked to their instability due to partial dissolution in the reaction medium. Further, this paper also reviews the proposed mechanisms of glycerol polymerization over alkaline-based catalysts and discuss the various operating conditions with an impact on the performances. More particularly, temperature and amount of catalyst proved to have a significant influence on glycerol conversion and on its polymerization extent.

The present paper deals with the stochastic modeling of bio-colonization for the computation of stochastic hydrodynamic loading on jacket-type offshore structures. It relies on a multidisciplinary study gathering biological and physical research fields that accounts of uncertainties at all the levels. Indeed, bio-colonization of offshore structures is a complex phenomenon with two major but distinct domains (i) marine biology whose processes are modeled with biomathematics methods and (ii) hydrodynamic processes. This paper aims to connect these two domains. It proposes a stochastic model for the marine organism’s growth and then continues with transfers for assessment of drag coefficient and forces probability density functions that accounts for marine growth evolution. A case study relies on the characteristics (growth and shape) of the blue mussel (Mytilus edulis) in northeastern Atlantic.

Cannabis has developed into a multi-billion dollar industry that relies on clonal propagation of elite genetics with desirable agronomic and chemical phenotypes. While the goal of clonal propagation is to produce genetically uniform plants, somatic mutations can accumulate during growth and compromise long-term genetic fidelity. Cryopreservation is a process in which tissues are stored at cryogenic temperatures, halting cell division and metabolic processes to facilitate high fidelity germplasm preservation. In this study, a series of experiments were conducted to optimize various stages of cryopreservation and develop a protocol for long-term germplasm storage of Cannabis sativa. The resulting protocol uses a standard vitrification procedure to cryopreserve nodal explants from in vitro shoots as follows: Nodes were cultured for 17 hours in a pre-culture solution (PCS), followed by a 20 minute treatment in a loading solution (LS), and a 60 minute incubation in plant vitrification solution 2 (PVS2). The nodes were then flash frozen in liquid nitrogen, re-warmed in an unloading solution at 40°C, and cultured on basal MS culture medium in the dark for 5 days followed by transfer to standard culture conditions. This protocol was tested across 13 genotypes to assess the genotypic variability. The protocol was successful across all 13 genotypes, but significant variation was observed in tissue survival (43.3-80%) and regrowth of shoots (26.7-66.7%). Plants grown from cryopreserved samples were morphologically and chemically similar to control plants for most major traits, but some differences were observed in the minor cannabinoid and terpene profiles. While further improvements are likely possible, this study provides a functional cryopreservation system that works across multiple commercial genotypes for long-term germplasm preservation.

The continuous growth of roots depends on their ability to maintain a balanced ratio between cell production and cell differentiation at the tip. This process was reported to be regulated by the hormonal balance of cytokinin and auxin. However, other important regulators, such as plant folates, have also been reported to play a regulatory role. In this study, we investigated the impact of the folate precursor PABA on root development. Using pharmacological, genetic, and imaging approaches, we show that the growth of Arabidopsis thaliana roots is repressed by either supplementing the growth medium with PABA or overexpressing the PABA synthesis gene GAT-ADCS. This is associated with a smaller root meristem size, which consists of fewer cells. Conversely, reducing the levels of free root endogenous PABA results in longer roots with extended meristems and increased cell numbers. We provide evidence that PABA represses Arabidopsis root growth in a folate-independent manner and likely acts through two mechanisms: (i) the G2/M transition of cell division in the root apical meristem and (ii) promoting premature cell differentiation in the transition zone. These data collectively suggest that PABA plays a role in Arabidopsis root growth at the point where cell division and cell differentiation intersect.

The purpose of this paper is to assess the degree of openness of scientific articles on bioeconomy. Based on a WoS corpus of 2,489 articles published between 2015 and 2019, we calculated bibliometric indicators, explored the openness of each paper and assessed the share of journals, countries and research areas of these articles. The results show a sharp increase and diversification of articles in the field of bioeconomy, with a beginning long tail distribution. 45.6% of the articles are freely available, and the share of OA papers is steadily increasing, from 31% in 2015 to 52% in 2019. Gold is the most important variant of OA. Open access is low in the applied research areas of chemical, agricultural and environmental engineering but higher in the domains of energy and fuels, forestry, and green and sustainable science and technology. The UK and the Netherlands have the highest rates of OA papers, followed by Spain and Germany. The funding rate of OA papers is higher than of non-OA papers. This is the first bibliometric study on open access to articles on bioeconomy. The results can be useful for the further development of OA editorial and funding criteria in the field of bioeconomy.

Home care centers face both an increase in demand and many variations during the execution of routes, compromising the routes initially planned: robust solutions are not effective enough, it is necessary to move on to resilient approaches. We create a close to reality use case supported by interviews of staff at home health care centers, where caregivers are faced with unexpected events that compromise their initial route. We model, analyze and compare three resilient approaches to deal with these disruptions: a baseline approach without any collaboration, a distributed collaborative approach, and a centralized collaborative approach, where we propose a centralization and sharing of information to improve local decision-making. The latter reduces the number of late arrivals by 11% and the total time of late arrival by 21%, and also halves the number of routes exceeding the end of work time (contrary to the distributed collaborative approach, due to the time wasted reaching colleagues). The use of a device, such as a smartphone application, to centralize and share information thus allows better mutual assistance between caregivers. Moreover, we highlight several possible openings like the coupling of simulation and optimization to propose a more resilient approach.

Introduction: The attitudes of doctors and nurses toward patient safety is a significant factor in hospital safety climates and medical error rates. Yet, there are very few studies of patient safety attitudes in Saudi hospitals and none conducted in hospital emergency departments. Aims: The current study aims to investigate the discrepancy between the patient safety attitudes of doctors and nurses in a Saudi hospital emergency department. Materials and Method: The study employed a qualitative research designvia semi-structured interviews with Saudi and non-Saudi doctors and nurses working in a Saudi hospital emergency department to determine their attitudes and experiences about the patient safety climate. Results: The findings showed doctors and nurse held some similar safety attitudes, however, nurses reported issues with doctors with respect to their teamwork, communication, and patient safety attitudes. Moreover, several barriers to the patient safety climate were identified such as limits to resources, teamwork, communication, and incident reporting. Conclusion: The findings provide one of the few research contributions to knowledge on the differential patient safety attitudes of Saudi and non-Saudi doctors and nurses and suggest the application of such knowledge would enhance positive patient outcomes in emergency departments.

Following the central dogma of molecular biology, gene expression heterogeneity can aid in predicting and explaining the wide variety of protein products, functions, and, ultimately, heterogeneity in phenotypes. There is currently overlapping terminology used to describe the types of diversity in gene expression profiles, and overlooking these nuances can misrepresent important biological information. Here, we describe transcriptome diversity as a measure of the heterogeneity in 1) the expression of all genes within a sample or a single gene across samples in a population (gene-level diversity) or 2) the isoform-specific expression of a given gene (isoform-level diversity). We first overview modulators and quantification of transcriptome diversity at the gene level. Then, we discuss the role alternative splicing plays in driving transcript isoform-level diversity and how it can be quantified. Additionally, we overview computational resources for calculating gene-level and isoform-level diversity for high-throughput sequencing data. Finally, we discuss future applications of transcriptome diversity. This review provides a comprehensive overview of how gene expression diversity arises, and how measuring it determines a more complete picture of heterogeneity across proteins, cells, tissues, organisms, and species.

Significant amounts of anthropogenic radionuclides were introduced in ocean waters following nuclear atmospheric tests and development of the nuclear industry. Dispersion of artificial dissolved radionuclides has been extensively measured for decades over the European continental shelf. The radionuclide measurement and release fluxes databases provided here represent an exceptional opportunity to validate dispersion hydrodynamic models. MARS hydrodynamic model have been applied at different scales to reproduce in realistic conditions the measured dispersion. Specific methods have been developed to obtain qualitative and quantitative results and perform model/measurement comparisons. Model validation concerns short to large scales with dedicated surveys following the dispersion: it was performed within two and three dimensions framework and from minutes and hours following a release up to several years. Results are presented concerning the dispersion of radionuclides in marine systems deduced from standalone measurements, or according to model comparisons. It allows characterising dispersion over the continental shelf, pathways, transit times, budgets and source terms. This review exhibits the main features retained from the point of view of radiotracers, hydrodynamic models and model/measurement methods with perspectives of applications in other areas or oceanographic domains.

This study presents the utilization of the Microwave InfraRed Thermography (MIRT) technique to identify and analyze the defects in the carbon-fiber-reinforced polymer (CFRP) composite rein-forcement of concrete specimens. At first, a set of the numerical models was created, comprising of the broadband pyramidal horn antenna and the analyzed specimen. The utilization the system operating at a power of 1000W in a continuous mode, operating at frequency of 2.45 GHz was analyzed. The specimen under examination comprised a compact concrete slab that was covered with an adhesive layer, thereafter, topped with a layer of CFRP. An air gap represented a defect at the interface between the concrete and CFRP within the adhesive layer. In the modelling stage the study investigated three separate scenarios: a sample with no defects, a sample with a defect located at the center, and a sample with a numerous additional random defects located at the rim of the CFRP matte, to analyze the effect of the natural reinforcement degradation in this area. The next phase of the study involved conducting experiments to confirm the results obtained from nu-merical modeling. In the experiments the concrete sample aged for 10 years with the defect in the center and naturally developed defects at the CFRP rim was used. The study employed numerical modeling to explore the phenomenon of microwave heating in complex structures. The aim was to assess the chosen antenna design and identify the most effective experimental setup. These con-clusions were subsequently confirmed through experimentation. The observations made during the heating process were particularly remarkable, since they deviated from earlier studies that solely conducted measurements of the sample post-heating phase. The findings demonstrate that MIRT has the capacity to be employed as a technique for detecting flaws in concrete structures reinforced with CFRP.

Four strains of green microalgae (Scenedesmus acutus, Scenedesmus vacuolatus, Chlorella sorokiniana and Chlamydomonas reinhardtii) were compared for growth and pigment composition under photoautotrophic or heterotrophic conditions. Batch growth experiments were performed in multicultivators with online monitoring of optical density. For photoautotrophic growth, light-limited (CO2-sufficient) growth was analysed under different light intensities during exponential and deceleration growth phases. The specific growth rate, mesured during exponential phase, and the maximal biomass productivity, measured during deceleration phase, were not related to each other when different light intensities and different species were considered. This indicates species-dependent photoacclimation effects during cultivation time, which was confirmed by light-dependent changes in pigment contents and compositions when exponential and deceleration phases were compared. Except for C. reinhardtii, that does not grow on glucose, heterotrophic growth was promoted to similar extents by acetate or by glucose, however these two substrates led to different pigment compositions. Weak light increased pigment contents during heterotrophy in the four species, but was efficient in promoting growth only in S. acutus. C. sorokiniana and S. vacuolatus exhibited the best potential for heterotrophic biomass productivities both on glucose and acetate, with carotenoid (lutein) content being the highest in the former.

With the rapid development of technology and the advancement of Internet technology, various social networking platforms are gradually coming into people's view and occupying a higher and higher position. In the recommendation scenario, the user-item interaction naturally forms a bipartite heterogeneous graph structure and with the development of graph embedding and graph neural network technologies based on deep learning to process graph domain information, the combination of graph information and recommendation systems shows strong research potential and application prospects. The methodological improvement of the recommendation algorithm based on collaborative filtering takes advantage of the nature that user-items can form a bipartite graph in the recommendation scenario. The existing methods still have some shortcomings. The methods that only use weights or convolutional recurrent neural networks to implicitly model different historical behaviors lack explicit modeling of video switching relationships in serialized behaviors. The user's interest is changing all the time, so it is not possible to recommend based on the user's history, and it is necessary to consider both the long-term and short-term interest of the user according to the video content in order to achieve accurate recommendation of short videos. In this paper, we design a recommendation model based on graph neural network, which models users' long-term and short-term interests by two vector propagation methods, respectively.

Electron Beam Melting (EBM) is an increasingly used Additive Manufacturing (AM) technique employed by many industrial sectors, including the medical device and aerospace industries. In EBM process monitoring, data analysis for processed layer quality evaluation is currently focused on the extraction of information from the raw data collected in-EBM process, i.e. thermal/ optical / electronic images, and the comparison between the collected data and the Computed Tomography (CT)/ microscopy images generated post-EBM process. This article postulates that a stack of bitmaps could be generated from the 3D model at a range of Z heights during file preparation of the EBM process, and serve as a reference image set. In-EBM process comparison between that and the workpiece images collected during the EBM process could then be used for quality assessment purposes. In addition, despite the extensive literature on 3D model slicing and contour generation for AM process preparation, no methods regarding image generation from cross sections of the 3D models have been disseminated in details. This article aims to address this by presenting a piece of 3D model-image generation software. The software is capable of generating binary 3D model reference images with user-defined Region-of-Interest (ROI) of the processing area, and Z heights of the model. It is envisaged that this 3D model-reference image generation ability opens up new opportunities in quality assessment for the in-process monitoring of the EBM process.

Although the vegetative stage of indoor cannabis production can be relatively short in duration, there is a high energy demand due to higher light intensities (LI) than the clonal propagation stage and longer photoperiods than the flowering stage (i.e., 16 – 24 hours vs. 12 hours). While electric lighting is a major component of both energy consumption and overall production costs, there is a lack of scientific information to guide cultivators in selecting a LI that corresponds to their vegetative stage production strategies. To determine the vegetative plant responses to LI, clonal plants of ‘Gelato’ were grown for 21 days with canopy-level photosynthetic photon flux densities (PPFD) ranging between 135 and 1430 µmol·m^-2·s^-1 on a 16-hour photoperiod (i.e., daily light integrals of ≈ 8 to 80 mol·m^-2·d^-1). Plant height and growth index responded quadratically; the number of nodes, stem thickness, and aboveground dry weight increased asymptotically; and internode length and water content of aboveground tissues decreased linearly with increasing LI. Foliar attributes had varying responses to LI. Chlorophyll content index increased asymptotically, leaf size decreased linearly and specific leaf weight increased linearly with increasing LI. Generally, PPFD levels of ≈ 900 µmol·m^-2·s^-1 produced compact, robust plants that are commercially relevant, while PPFD levels of ≈ 600 µmol·m^-2·s^-1 promoted plant morphology with more open architecture – to increase airflow and reduce the potential foliar pests in compact (i.e., indica-dominant) genotypes.

The manipulation of participant allocation in randomized controlled trials to achieve equal groups sizes may introduce allocation bias potentially leading to larger treatment effect estimates. This study aimed to estimate the proportion of nursing trials that have precisely equal group sizes and examine if there was an association with trial outcome. Data were extracted from a sample of 148 randomized controlled trials published in nursing science journals in 2017. One hundred trials (68%) had precisely equal group sizes. Respectively, a positive outcome was reported in 70% and 58% of trials with equal/unequal groups. Trials from Asia were more likely to have equal group sizes than those from the rest of the world. Most trials reported a sample size calculation (n=105, 71%). In a third of trials (n=36, 34%), the number of participants recruited precisely matched the requirement of the sample size calculation; this was significantly more common in studies with equal group sizes. The high number of nursing trials with equal groups may suggest nurses con-ducting clinical trials are manipulating participant allocation to ensure equal group size increasing the risk of bias.

Metastasis is a critical step in the process of carcinogenesis and a vast majority of cancer related mortalities result from metastat-ic disease that is resistant to current therapies. Cell migration and invasion are the first steps of the metastasis process, which mainly occurs by two important biological mechanisms i.e., cytoskeletal remodelling and Epithelial to Mesenchymal Transition (EMT). Akt (also known as Protein Kinase B) is a central signalling molecule of the PI3K-Akt signalling pathway. Aberrant acti-vation of this pathway has been identified in a wide range of cancers. Several studies have revealed that Akt actively engages with the migratory process in motile cells, including metastatic cancer cells. The downstream signalling mechanism of Akt in cell migration depends upon the tumour type, sites, and intracellular localisation of activated Akt. In this review, we focus on the role of Akt in the regulation of two events that control cell migration and invasion in various cancers including head and neck squamous cell carcinoma (HNSCC) and the status of PI3K-Akt pathway inhibitors in clinical trials in HNSCC.

There is some evidence that aspects of nurse-doctor communication are associated with the quality of care and treatment patients receive whilst they are in hospital. To date, no studies have examined stakeholder perceptions of how patient care is influenced by clinical communication between nurses and doctors. We conducted a concept mapping study to generate a deep understanding of how clinical communication impacts patient care. Concept mapping has six phases: preparation, idea generation, structuring, representation, interpretation, and utilization. Twenty patients, 21 nurses, and 21 doctors participated in the study. Brainstorming generated 69 discreet statements about how nurse-doctor communication impacts patient care. The structuring (rating and clustering) phase was completed by 48 participants. The data interpretation workshop selected a five-cluster solution: effective communication, trust, patient safety, impediments to patient care, and interpersonal skills. On the final concept map, the five clusters were arranged in a circle around the center of the map. Clusters were relatively equal in size suggesting, each concept makes a broadly equal contribution to how nurse-doctor communication influences patient care. Our study suggests that there are multiple aspects of clinical communication that impact patient care. Candidate interventions to enhance nurse-doctor communication may need to consider the complex nature of interprofessional working. Registration: This study was prospectively registered with the Open Science Framework (OSF) (https://osf.io/9np8v/) prior to recruiting the first participant.

Following legalization, cannabis has quickly become an important horticultural crop in Canada and increasingly so in other parts of the world. However, due to previous legal restrictions on cannabis research there are limited scientific data on the relationship between nitrogen (N), phosphorus (P), and potassium (K) supply (collectively: NPK) and the crop yield and quality. This study examined the response of a high delta-9-tetrahydrocannabinol (THC) Cannabis sativa cultivar grown in deep-water culture with different nutrient solution treatments varying in their concentrations (mg L^-1) of N (70, 120, 180, 250, 290), P (20, 40, 60, 80, 100) and K (60, 120, 200, 280, 340) according to a central composite design. Results demonstrated that inflorescence yield responded quadratically to N and P, with the optimal concentrations predicted to be 194 and 59 mg L^-1, respectively. Inflorescence yield did not respond to K in the tested range. These results can provide guidance to cultivators when formulating nutrient solutions for soilless cannabis production and demonstrates the utility of surface response design for efficient multi-nutrient optimization.

Most commercial Cannabis sativa L. (cannabis) genotypes are short-day plants and cultivators typically use a 12.0 h uninterrupted dark period to induce flowering; however, scientific information is lacking to prove this is the optimal dark period for all genotypes, and cultivar specific photoperiods may increase productivity. Tissue culture can be used for research requiring multiple treatments, proper replication, and in a controlled environment on a smaller scale compared to greenhouse and indoor facilities. To determine whether cannabis explants can flower under varied photoperiods in vitro, explants were grown under one of six photoperiod treatments: 12.0, 13.2, 13.8, 14.4, 15.0, and 16.0 h for four weeks. The percentage of flowering explants was highest under 12.0 and 13.2 h treatments. There were no treatment effects on the fresh weight, final height, or growth index of the explants. The results suggest an uninterrupted dark period of at least 10.8 h (i.e. 13.2 h photoperiod) is needed to induce the flowering of this genotype. In vitro flowering could provide a unique and high throughput approach to study floral/seed development and secondary metabolism in cannabis under highly controlled conditions. Further research should determine if this response is the same on a whole plant level.

Over the last few decades, many countries, especially Caribbean island ones, have been challenged by the devastating consequences of natural disasters, which pose a significant threat to human health and safety. Timely information related to the distribution of vulnerable population and critical infrastructure are key for an effective disaster relief. OpenStreetMap (OSM) has repeatedly been shown to be highly suitable for disaster mapping and management. However, large portions of the world, including countries exposed to natural disasters, remain unmapped. In this study, we propose a methodology that relies on remotely sensed measurements (e.g. VIIRS, Sentinel-2 and Sentinel-1) and derived classification schemes (e.g. forest and built-up land cover) to predict the completeness of OSM building footprints in three small island states (Haiti, Dominica and St. Lucia). We find that the combinatorial effects of these predictors explain up to 94% of the variation of the completeness of OSM building footprints. Our study extends the existing literature by demonstrating how remotely sensed measurements could be leveraged to evaluate the completeness of OSM database, especially in countries at high risk of natural disasters. Identifying areas that lack coverage of OSM features could help prioritize mapping efforts, especially in areas vulnerable to natural hazards and where current data gaps pose an obstacle to timely and evidence-based disaster risk management actions.

The identification of informal settlements in urban areas is an important step in developing and implementing pro-poor urban policies. Understanding when, where and who lives inside informal settlements is critical to efforts to improve their resilience. This study aims to analyse the capability of machine-learning (ML) methods to map informal areas in Jeddah, Saudi Arabia, using very-high-resolution (VHR) imagery and terrain data. Fourteen indicators of settlement characteristics were derived and mapped using an object-based ML approach and VHR imagery. These indicators were categorised according to three different spatial levels: environ, settlement and object. The most useful indicators for prediction were found to be density and texture measures, (with random forest (RF) relative importance measures of over 25% and 23% respectively). The success of this approach was evaluated using a small, fully independent validation dataset. Informal areas were mapped with an overall accuracy of 91%. Object-based ML as a hybrid approach performed better (8%) than object-based image analysis alone due to its ability to encompass all available geospatial levels.

We describe a new approach for integrating multiple views of data into a common latent space using non-negative tensor factorization (NTF). This approach, which we refer to as the "Integrated Sources Model" (ISM), consists of two main steps: embedding and analysis. In the embedding step, each view is transformed into a matrix with common non-negative components. In the analysis step, the transformed views are combined into a tensor and decomposed using NTF. Noteworthy, ISM can be extended to process multi-view data sets with missing views. We illustrate the new approach using two examples: the UCI digit dataset and a public cell type gene signatures dataset, to show that multi-view clustering of digits or marker genes by their respective cell type is better achieved with ISM than with other latent space approaches. We also show how the non-negativity and sparsity of the ISM model components enable straightforward interpretations, in contrast to latent factors of mixed signs. Finally, we present potential applications to single-cell multi-omics and spatial mapping, including spatial imaging and spatial transcriptomics, and computational biology, which are currently under evaluation. ISM relies on state-of-the-art algorithms invoked via a simple workflow implemented in a Jupyter Python notebook.

Modification of Scots pine sapwood (Pinus sylvestris L.) with heterocyclic compounds, imidazole and succinimide, was investigated. Pressure-impregnation with aqueous solutions containing imidazole, imidazole + citric acid, succinimide, succinimide + citric acid, and citric acid + sorbitol (CIOL®) at 5%, 10%, and 15% solid content was followed by oven-curing at 220 °C for 1 hour. Mass changes during treatment steps, bending properties, and anti-swelling efficiency (ASE) were examined. Results indicate that solid concentrations within the range of 5% to 10% were optimal. Results seem to show there are two differing mechanisms in the modification of imidazole and succinimide, respectively. Mass loss due to the heat treatment was highest in imidazole-treated specimens, whereas it remained low and concentration-independent in succinimide-treated specimens. ASE after three cycles reached 31% for imidazole-treated specimens and improved to 38% with the addition of citric acid. For succinimide, ASE increased from 17% to 41%. Bending properties generally showed improvement, except for succinimide + citric acid and CIOL®, which displayed a reduced modulus of rupture. Chemical analyses are warranted to fully understand the reaction mechanisms of the treatments. Imidazole treatment's positive effects are suggested to stem from a thermal reaction between the chemical and wood, indicated by substantial mass loss during leaching and specimen darkening. Succinimide and citric acid might exhibit polymerization with each other and wood components, akin to the CIOL® process. Further research should delve into reaction mechanisms and the impact of imidazole and succinimide on biological durability.

Acetaminophen use during pregnancy and early childhood was accepted in the 1970s, but is now a subject of considerable concern. Careful analysis shows that initial acceptance of the drug was based on false assumptions and ignorance of the impact of the drug on brain development. Fourteen studies now indicate that prenatal exposure to acetaminophen is associated with neurodevelopmental problems. Based on corrections for confounding factors applied to the analyses of available data, it can be concluded that prenatal exposure to acetaminophen causes statistically significant risks of one subtype of autism spectrum disorder (ASD), developmental delays, and attention deficit hyperactivity disorder. In contrast, data regarding postnatal exposure to acetaminophen are limited, and several factors impede a classic multivariate analysis of data to resolve the issue. However, circumstantial evidence regarding postnatal exposure to the drug is abundant, and it can be concluded beyond a reasonable doubt that postnatal exposure to acetaminophen in susceptible children is responsible for many if not most cases of ASD. Circumstantial evidence includes at least three otherwise unexplained temporal relationships, data from laboratory animal studies, several miscellaneous and otherwise unexplained correlations, and the lack of alternative suspects that fit the evidence-derived profile.

The supply chain has incorporated products by putting them into hair scarfs. This study introduces the use of mini chips in health and beauty products and can reduce fatigue through enhanced sleep patterns. The mini chip could be placed in the scarf and used as a prototype. RFID technology provides the supply chain with specific information that is used to identify products and make communication easier. (Muhammad, et. al. 2013) This paper presents a new tool herein referred to as a scarf prototype which is developed to analyse EMG (electromyogram), ECG (electrocardiography), EEG (electroencephalogram), and EOG (electro-oculogram) signals that focuses in the area of sleep disorders. The mini chips used can be used to determine a solution for sleep disruption by using automated analytics. This could lead to improvement in our understanding of sleep disruption and overall sleep physiology. Automated technology allows repeated measurements, evaluation of sleep patterns, and provide suggestions to improve a person’s quality of sleep. This analysis compares the use of polysomnography and the scarf prototype. The analytics provide models and shows correlation between variables, such as EMG, ECG, EEG, and EOG. This study shows that the results from the scarf prototype is just as reliable as the original method, polysomnography.

In agriculture, the intricate relationship between innovation, productivity, and entrepreneurship is underexplored. Despite the widely recognised role of innovation in driving productivity, concrete indicators and comprehensive farm-level studies are lacking. This research aims to unravel this complexity by exploring the impact of innovation, specifically in agricultural entrepreneurship, on transformative changes in farm productivity. Using a two-stage analysis with the Malmquist Index (MI) of total factor productivity (TFP) on cereal farms from the Farm Business Survey (FBS) over 11 years, the study identifies innovators and, it assesses changes in productivity, technical efficiency, and economic efficiency. The second stage decomposes the MI to understand factors enabling innovation, including changes in technology scale. Objectives include a literature review to map innovation variables, integrating FBS data for validation and assessing productivity impacts from asset enhancements and changes in farming scale. Results reveal significant productivity variation and a moderate overall improvement. Future research directions emphasize expanded data collection on managerial behaviours and technology investments' role in efficiency frontier shifts. The study concludes by emphasising nuanced agricultural policies that leverage farmers' knowledge for innovation through enhanced management efficiency. It advocates for a departure from the 'bigger is better' mentality, proposing educational programs and support services to encourage informed decision-making. This forward-looking approach aims to inform future policies and enhance understanding of the intricate dynamics between agricultural innovation, productivity, and entrepreneurship.

AbstractWhile the technology is relatively new, low cost 3D printing has impacted many aspects of human life. 3D printers are being used as manufacturing tools for a wide variety of devices in a spectrum of applications ranging from diagnosis to implants to external prostheses. The ease of use and availability of 3D design software and low cost has made 3D printing an accessible manufacturing and fabrication tool in many research laboratories. 3D printers can print materials with varying density, optical character, strength and chemical properties providing platforms for a huge number of strategies that can be chosen for user’s needs. In this review, we focus on applications in biomedical diagnostics and how this revolutionary technique is facilitating development of low cost, sensitive and often geometrically complex tools. 3D printing in fabrication of microfluidics, supporting equipment, optical and electronic components of diagnostic devices is presented. Emerging diagnostic 3D bioprinting as a tool to incorporate living cells or biomaterials into 3D printing is also discussed.

The recent legalization of Cannabis sativa L. in many regions has revealed a need for effective propagation and biotechnologies for the species. Micropropagation affords researchers and producers methods to rapidly propagate insect/disease/virus free clonal plants, store germplasm, and forms the basis for other biotechnologies. Despite this need, research in the area is limited due to the long history or prohibitions and restrictions. Existing literature has multiple limitation: many publications use hemp as a proxy for drug-type Cannabis when it is well established that there is significant genotype specificity, studies using drug-type cultivars are predominantly op-timized using a single cultivar, most protocols have not been replicated by independent groups, and some attempts demonstrate a lack of reproducibility across genotypes. Due to culture decline and other problems the multiplication phase of micropropagation (stage 2) has not been fully developed in many reports. This review will provide a brief background on the history and botany of Cannabis as well as a comprehensive and critical summary of Cannabis tissue culture. Special attention will be paid to current challenges faced by researchers, the limitations of existing Cannabis micropropagation studies, and recent developments and future directions of Cannabis tissue culture technologies.

Process mining offers significant services in the development of digital threads and digital twin applications for healthcare. One of the sub-emerging case studies is the use of patients’ location data in process mining analyses. While the streamlining of published works is focused on introducing process discovery algorithms, there is a necessity to address challenges beyond that. Literature analysis indicates that explainability, reasoning, and characterizing the root causes of process drifts in healthcare processes is an important but overlooked challenge. In addition, incorporating domain-specific knowledge into process discovery could be a significant contribution to process mining literature. To address this, we present the DIAG approach that consists of a meta-model and an algorithm that enables diagnosing in process mining through an ontology-driven approach. With DIAG, we modeled the healthcare semantics in a process mining application and diagnosed the causes of drifts in patients’ pathways. We performed an experiment in a hospital living lab to examine the effectiveness of the DIAG approach.

Characterised by the growth of benign tumours, fibropapillomatosis (FP) is a debilitating disease that predominantly afflicts the endangered green turtle (Chelonia mydas). A growing body of histological and molecular evidence has consistently associated FP tumours with Chelonid alphaherpesvirus 5 (ChHV5), leading this virus to be considered the most likely aetiological agent of FP. However, a recent study which detected both ChHV5 and Chelonia mydas papillomavirus 1 (CmPV1) DNA in FP tumour tissues has challenged this hypothesis. The present study aimed to establish the wider prevalence of CmPV1 and co-occurrence with ChHV5 in marine turtles in waters adjacent to the east coast of Queensland, Australia. This comprehensive molecular survey screened a total of 353 samples from 275 foraging turtles using probe-based qPCR. Three sample categories were used in this study: Group A (FP tumours), Group B (non-tumoured skin from turtles with FP tumours) and Group C (non-tumoured skin from turtles without FP tumours). Concurrent detection of ChHV5 and CmPV1 DNA is reported for all three categories, with the highest rate of concurrent detection reported for Group A samples (43.5%). Collectively, these results pivot the way we think about FP; as an infectious disease where two separate viruses may be at play.

In this retrospective report we present five cases of critically ill pregnant or newly delivered women positive for Covid-19 admitted to our obstetrical departments at Karolinska University Hospital. They compose 6% of eighty-three pregnant women that tested positive for SARS-CoV-2 during the period March 25 to May 4, 2020. Three patients were at the time of admission in gestational week between 21+4 to 22+5 and treated during their antenatal period, meanwhile the other two were admitted within 1 week postpartum. All of them were in a need of intensive care, one was treated with high flow oxygen therapy, the other four with invasive mechanical ventilation (three with endotracheal intubation and one with extra corporeal membrane oxygenation). Age above thirty, overweight and gestational diabetes are notable factors in the cases presented. At the time of admission, they all presented with symptoms as fever, cough and dyspnea. Chest imaging with computer tomography scan was performed in each case and demonstrated multifocal pneumonic infiltrates in all of them but no pulmonary embolism was confirmed in any. Neither did the echocardiogram indicates any cardiomyopathy. Four of the patients have been discharged from the hospital, with an average of 20 hospital days. One antenatal pregnant woman needed prolonged ECMO therapy, in gestational week 27+3 she went into cardiac arrest, resulting in an urgent c-section on maternal indication. At the time of writing she is still hospitalized. In coherence with other published reports our cases indicate that critically ill pregnant women infected by SARS-Cov-2 may develop severe respiratory distress syndrome requiring prolonged intensive care. The material is limited for conclusions to be taken, more detailed information on symptoms, treatment, and outcomes for pregnant and postpartum women managed in intensive care is therefore needed.

With rising rates of human obesity, the study aimed to determine the relationship between maternal diet-induced obesity and offspring morphometrics and behaviour in mice. Pregnant and lactating female mice fed a diet high in fat and sugar (HFHS) commonly consumed by human populations showed decreased food, calorie, and protein intake but increased adiposity at the expense of lean mass. The pre-weaning body weight of HFHS offspring was reduced for the first postnatal week but not thereafter with HFHS female offspring having higher body weights by weaning, due to continuing higher fractional growth rates. Post-weaning, there were minor differences in offspring food and protein intake. Maternal diet, however, affected fractional growth rate and total body fat content of male but not female HFHS offspring. Maternal diet did not affect offspring locomotor activity or social behaviour in either sex. Both male and female HFHS offspring displayed reduced anxiety-related behaviours with sex differences in particular aspects of the elevated plus maze task. In the novel object recognition task, performance was impaired in male but not female HFHS offspring. Collectively, the findings demonstrate that maternal obesity alters the growth, adiposity, and behaviour of male and female offspring, with sex-specific differences.

Passive plasma spectroscopy is a well-established non-intrusive diagnostic technique. Depending on the emitter and its environment which determine the dominant interactions and effects governing emission line shapes, passive spectroscopy allows the determination of electron densities, emitter and perturber temperatures as well as other quantities like abundances. However, using spectroscopy needs appropriate line shape codes retaining all the physical effects governing the emission line profiles. This requires for line shape code developers to continuously correct or improve them to increase their accuracy when applied for diagnostics. This is exactly the aim expected from code-code and code-data comparisons. In this context, the He I 492 nm emitted in a helium corona discharge at room temperature represents an ideal case since its profile results from several broadening mechanisms: Stark, Doppler, resonance and van der Waals. The importance of each broadening mechanism depends on the plasma parameters. Here the profiles of the He I 492 nm in a helium plasma computed by various codes are compared for a selected set of plasma parameters. In addition, preliminary results related to plasma parameter determination using experimental spectra from a helium corona discharge at low pressure 1- 2 bars, are presented.

Understanding the factors which control endothelial cell (EC) function and angiogenesis is crucial for developing the horse as a disease model, but equine ECs remain poorly studied. In this study we have optimised methods for the isolation and culture of equine aortic endothelial cells (EA-oECs) and characterised their angiogenic functions in vitro. Mechanical dissociation, followed by magnetic purification using an anti-VE-cadherin antibody, resulted in EC-enriched cultures suitable for further study. Fibroblast growth factor 2 (FGF2) increased EAoEC proliferation rate and stimulated scratch wound closure and tube formation by EAoECs on extracellular matrix. Pharmacological inhibitors of FGFR1 (SU5402) or MEK (PD184352) blocked FGF2-induced ERK1/2 phosphorylation and functional responses, suggesting that these are dependent on FGFR1/MEK-ERK signalling. In marked contrast, VEGF-A had no effect on EAoEC proliferation, migration or tubulogenesis and did not promote ERK1/2 phosphorylation, indicating a lack of sensitivity to this classical pro-angiogenic growth factor. Gene expression analysis showed that, unlike human ECs, FGFR1 is expressed by EAoECs at a much higher level than both VEGFR1 and VEGFR2. These results suggest a predominant role for FGF2 versus VEGF-A in controlling the angiogenic functions of equine ECs. Collectively, our novel data provide a sound basis for stud-ying angiogenic processes in the horse and lay the foundations for comparative studies of EC biology in horses versus humans.

Osteoarthritis and rheumatoid arthritis are two of the most common chronic inflammatory joint diseases, for which there remains a great clinical need to develop safer and more efficacious pharmacological treatments. The pathology of both osteoarthritis and rheumatoid arthritis involves multiple tissues within the joint, including the synovial joint lining and the bone, as well as the articular cartilage in osteoarthritis. In this review, we discuss the potential for the development of oligonucleotide therapies for these disorders by examining the evidence that oligonucleotides can modulate the key cellular pathways that drive the pathology of the inflammatory diseased joint pathology as well as evidence in preclinical in vivo models that oligonucleotides can modify disease progression.

Expression of Krüppel–like factor 15 (KLF15), a stress induced transcription factor, is induced during bovine herpesvirus 1 (BoHV-1) reactivation from latency, and KLF15 stimulates BoHV-1 replication. Transient transfection studies revealed KLF15 and glucocorticoid receptor (GR) cooperatively transactivate the BoHV-1 immediate early transcription unit 1 (IEtu1), herpes sim-plex virus type 1 (HSV-1) infected cell protein 0 (ICP0), and ICP4 promoter. The IEtu1 promoter drives expression of bICP0 and bICP4, two key BoHV-1 transcriptional regulatory proteins. Based on these studies, we hypothesized infection is a stressful stimulus that increases KLF15 ex-pression and enhances productive infection. New studies demonstrated that silencing KLF15 impaired HSV-1 productive infection and KLF15 steady state protein levels were increased at late stages of productive infection. KLF15 was primarily localized to the nucleus following in-fection of cultured cells with HSV-1, but not BoHV-1. When cells were transfected with a KLF15 promoter construct and then infected with HSV-1, promoter activity was significantly increased. The ICP0 gene and to a lesser extent bICP0 transactivated the KLF15 promoter in the absence of other viral proteins. In contrast, BoHV-1 or HSV-1 encoded VP16 had no effect on KLF15 pro-moter activity. Collectively, these studies revealed HSV-1 and BoHV-1 productive infection in-creased KLF15 steady state protein levels, which correlated with increased virus production.

Zika virus (ZIKV) is a flavivirus that originated in Africa but emerged in Latin America in 2015. In this region, other flaviviruses such as Dengue (DENV), West Nile, and Yellow Fever Virus (YFV) also circulate, allowing for possible antigenic cross-reactivity to impact viral infections and immune responses. Studies have found antibody mediated enhancement between DENV and ZIKV, but the impact of YFV antibodies on ZIKV infection has not been fully explored. ZIKV infections cause congenital syndromes, such as microcephaly, necessitating further research into ZIKV vertical transmission through the placental barrier. Recent advancements in biomedical engineering have generated co-culture methods that allow for in vitro recapitulation of the maternal: fetal interface. This study utilized a transwell assay, which is a co-culture model utilizing human placental syncytiotrophoblasts, fetal umbilical cells, and a differentiating embryoid body to replicate the maternal: fetal axis. To determine if cross reactive YFV vaccine antibodies impact the pathogenesis of ZIKV across the maternal fetal axis, maternal syncytiotrophoblasts were inoculated with ZIKV or ZIKV incubated with YFV vaccine anti-sera, and viral load was measured 72 hours post inoculation. Here we report that BeWo and HUVEC cells are permissive to ZIKV and that the impact of YFV post-vaccination antibodies on ZIKV replication is cell line dependent. Embryoid bodies are also permissive to ZIKV and the presence of YFV antibodies collected 1 to 6 months post vaccination enhances ZIKV infection. Our data show that each of the cell lines and EBs have a unique response to ZIKV complexed with post-vaccination serum suggesting there may be cell-specific mechanisms that impact congenital ZIKV infections. Since ZIKV infections can cause severe congenital syndromes, it is crucial to understand any potential enhancement or protection offered from cross-reactive, post-vaccination antibodies.

Zika virus (ZIKV) is a flavivirus that originated in Africa but emerged in Latin America in 2015. In this region, other flaviviruses such as Dengue (DENV), West Nile, and Yellow Fever Virus (YFV) also circulate, allowing for possible antigenic cross-reactivity to impact viral infections and immune responses. Studies have found antibody mediated enhancement between DENV and ZIKV, but the impact of YFV antibodies on ZIKV infection has not been fully explored. ZIKV infections cause congenital syndromes, such as microcephaly, necessitating further research into ZIKV vertical transmission through the placental barrier. Recent advancements in biomedical engineering have generated co-culture methods that allow for in vitro recapitulation of the maternal: fetal interface. This study utilized a transwell assay, which is a co-culture model utilizing human placental syncytiotrophoblasts, fetal umbilical cells, and a differentiating embryoid body to replicate the maternal: fetal axis. To determine if cross reactive YFV vaccine antibodies impact the pathogenesis of ZIKV across the maternal fetal axis, maternal syncytiotrophoblasts were inoculated with ZIKV or ZIKV incubated with YFV vaccine anti-sera, and viral load was measured 72 hours post inoculation. The data show that the impact of YFV on ZIKV replication is cell line dependent. In differentiating embryoids, the presence of YFV antibodies enhanced ZIKV infection. Since viral pathogenesis, and the impact of antigenic cross-reactive antibodies, is cell line specific at the maternal-fetal axis, this suggests there may be discreet mechanisms that impact congenital ZIKV infections.

After a local pollution control plant significantly reduced phosphorus loading into a phytoplankton-dominated tributary of the Potomac River in the early 1980’s, water quality and biological communities were monitored bi-weekly from April-September. After a 10-year time-lag, submerged aquatic vegetation (SAV), once abundant in this freshwater tidal embayment, returned to the area in 1993. After additional reductions in nitrogen load starting in 2000, the system completely switched to a SAV-dominated state in 2005. Fish abundance didn’t change during these distinct phase changes, but the fish community structure did. Increases in SAV provided refuge and additional spawning substrate for species with adhesive eggs such as Banded Killifish (Fundulus diaphanus), which is now the most abundant species in the embayment. Other changes seen were a decrease in the relative contribution of open water dwelling species such as White Perch (Morone americana), and an increase of visual predators such as Largemouth Bass (Micropterus salmoides). The 30-year record of data from this Potomac River tributary has revealed many important long-term trends that validate the effectiveness of initiatives to improve water treatment, and will aid in the continued management of the watershed and point source inputs.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a characteristic dysregulated metabolism. Abnormal clinicopathological features linked to defective metabolic and inflammatory response pathways can induce PDAC development and progression. In this study, we investigated the metabolites and lipoproteins profiles of PDAC patients of African ancestry. Nuclear Magnetic Resonance (NMR) spectroscopy was conducted on serum obtained from consenting individuals (34 PDAC, 6 Chronic Pancreatitis, and 6 healthy participants). Seventy-five signals were quantified from each NMR spectrum. The Liposcale test was used for lipoprotein characterization. Spearman’s correlation and Kapan Meier tests were conducted for correlation and survival analyses respectively. In our patient cohort, the results demonstrated that levels of metabolites involved in the glycolytic pathway increased with the tumour stage. Raised ethanol and 3-hydroxybutyrate were independently correlated with a shorter patient survival time, irrespective of tumour stage. Furthermore, increased levels of bilirubin resulted in an abnormal lipoprotein profile in PDAC patients. Additionally, we observed that the levels of a panel of metabolites (such as glucose, lactate) and lipoproteins correlated with those of inflammatory markers. Taken together, the metabolic phenotype can help distinguish PDAC severity and be used in predicting patient survival and in informing treatment intervention.

Obesity is treatment-resistant, and is linked with a number of serious, chronic diseases. Adult obesity rates in the United States have tripled since the early 1960s. Recent reviews show that an increased ratio of omega-6 to omega-3 fatty acids contributes to obesity rates by increasing levels of the endocannabinoid signals AEA and 2-AG, overstimulating CB₁R and leading to increased caloric intake, reduced metabolic rates, and weight gain. Cannabis, or THC, also stimulates CB₁R and increases caloric intake during acute exposures. The present meta-analysis reveals significantly reduced body mass index and rates of obesity in Cannabis users, in conjunction with increased caloric intake. We provide for the first time a causative explanation for this paradox, in which rapid and long-lasting downregulation of CB₁R following acute Cannabis consumption reduces energy intake and storage and increases metabolic rates, thus reversing the impact on body mass index of elevated dietary omega-6/omega-3 ratios.

Sub-Saharan social-ecological systems are undergoing changes in environmental conditions, including modifications in rainfall pattern and biodiversity loss. Consequences of such changes depend on complex causal chains which call for integrated management strategies whose efficiency could benefit from ecosystem dynamic modelling. However, ecosystem models often require lots of quantitative information for estimating parameters, which is often unavailable. Alternatively, qualitative modelling frameworks have proved useful for explaining ecosystem response to perturbations, while requiring fewer information and providing more general predictions. However, current qualitative methods have some shortcomings which may limit their utility for specific issues. In this paper, we propose the Ecological Discrete-Event Network (EDEN), an innovative qualitative dynamic modelling framework based on "if-then" rules which generates many alternative event sequences (trajectories). Based on expert knowledge, observations and literature, we use this framework to assess the effect of permanent changes in surface water and herbivores diversity on vegetation and socio-economic transitions in an East African savanna. Results show that water availability drives changes in vegetation and socio-economic transitions, while herbivore functional groups had highly contrasted effects depending on the group. This first use of EDEN in a savanna context is promising for bridging expert knowledge and ecosystem modelling.

Fire detection from satellite sensors relies on an accurate estimation of the unperturbed state of a target pixel, from which an anomaly can be isolated. Methods for estimating the radiation budget of a pixel without fire depend upon training data derived from the location's recent history of brightness temperature variation over the diurnal cycle, which can be vulnerable to cloud contamination and the effects of weather. This study proposes a new method that utilises the common solar budget found at a given latitude in conjunction with an area's local solar time to aggregate a broad-area training dataset, which can be used to model the expected diurnal temperature cycle of a location. This training data is then used in a temperature fitting process with the measured brightness temperatures in a pixel, and compared to pixel-derived training data and contextual methods of background temperature determination. Results of this study show similar accuracy between clear-sky medium wave infrared upwelling radiation and the diurnal temperature cycle estimation compared to previous methods, with demonstrable improvements in processing time and training data availability. This method can be used in conjunction with brightness temperature thresholds to provide a baseline for upwelling radiation, from which positive thermal anomalies such as fire can be isolated.

The goal of this article was to evaluate the antioxidant and anti-inflammatory like activities of three species from genus Primula L. growing in Georgia: Primula macrocalyx, Primula woronowii and Primula saguramica . First, fractions containing shoot and root parts were air-dried, grinded and extracted by 80% ethanol followed by condensation and freeze-drying. Second, further chromatographic separations were done on Diaion HP-20 with the following solvents: H2O, methanol (50% and 100 %) and ethylacetate 100% to obtain the expected fractions.

P-band radar remote sensing applied during the Airborne Microwave Observatory of Subcanopy and Subsurface (AirMOSS) mission has shown great potential for estimation of root zone soil moisture. When retrieving the soil moisture profile (SMP) from P-band radar, a mathematical function describing the vertical moisture distribution is required. Because only a limited number of observations are available, the number of free parameters of the mathematical model must not exceed the number of observed data. For example, a second order polynomial that contains 3 free parameters was presumed based on in-situ SMP data. The polynomial is currently parameterized based on 3 backscatter observations provided by AirMOSS (i.e. one frequency at three polarizations of HH, VV and HV). In this paper, a more realistic, physically-based SMP model containing 3 free parameters is derived based on a solution to Richards’ equation for unsaturated flow in soils. Evaluation of the new SMP model based on both numerical simulations and measured data revealed that it exhibits greater flexibility for fitting measured and simulated SMPs than the currently applied polynomial. It is also demonstrated that the new SMP model can be reduced to a second order polynomial at the expense of fitting accuracy.

Electron Beam Melting (EBM) is an increasingly used Additive Manufacturing (AM) technique employed by many industrial sectors, including the medical device and aerospace industries. The application of this technology is, however, challenged by the lack of process monitoring and control system that underpins process repeatability and part quality reproducibility. An electronic imaging system prototype has been developed to serve as an EBM monitoring technique, the capabilities of which have been verified at room temperature and at 320+10°C. Nevertheless, in order to fully assess the applicability of this technique, the image quality needs to be investigated at a range of elevated temperatures to fully understand the influence of thermal noise due to heat. In this paper, electronic imaging pilot trials at elevated temperatures, ranging from room temperature to , were carried out. Image quality measure Q of the digital electron images was evaluated, and the influence of temperature was investigated. In this study, raw electronic images generated at higher temperatures had greater Q values, i.e. better global image quality. It has been demonstrated that, for temperatures between , the influence of temperature on electronic image quality was not adversely affecting the visual clarity of image features. It is envisaged that the prototype has significant potential to contribute to in-process EBM monitoring in many manufacturing sectors.

Hepatic macrophages act as the liver’s first line of defense against injury. Their differentiation into pro-inflammatory or anti-inflammatory subpopulations is a critical event that maintains a delicate balance between liver injury and repair. In our investigation, we explored the influence of the small heterodimer partner (SHP), a nuclear receptor primarily associated with metabolism, on macrophage differentiation during the innate immune response. During macrophage differentiation, we observed significant alterations in Shp mRNA expression. Deletion of SHP promoted M1 differentiation while interfering with M2 polarization. Conversely, overexpression of SHP resulted in increased expression of peroxisome proliferator activated receptor gamma (Pparg), a master regulator of anti-inflammatory macrophage differentiation, thereby inhibiting M1 differentiation. Upon lipopolysaccharide (LPS) injection, there was a notable increase in the pro-inflammatory M1-like macrophages, accompanied by exacerbated infiltration of monocyte-derived macrophages (MDMs) into the livers of Shp myeloid cell specific knockout (Shp-MKO). Concurrently, we observed significant induction of tumor necrosis factor alpha (Tnfa) and chemokine (C-C motif) ligand 2 (Ccl2) expression in LPS-treated Shp-MKO livers. Additionally, the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-kB) pathways were activated in LPS-treated Shp-MKO livers. Consistently, both pathways were hindered in SHP overexpression macrophages. Finally, we demonstrated that SHP interacts with p65, thereby influencing macrophage immune repones. In summary, our study uncovered a previously unrecognized role of SHP in promoting anti-inflammatory macrophage differentiation during the innate immune response. This was achieved by SHP acting as a regulator for the Pparg, MAPK and NF-kB pathways.

Urban development and planning are increasingly centered on matters of sustainability, balancing economic development with ecosystem services and biotic structures within urban environments. In addition to these institutional and structural factors, the decision-making process within individual households must be understood to address rising concerns about water use. Therefore, individual characteristics and preferences that influence the use of water also warrant examination. In response to a survey of occupants of single-family residences in the Fresno Clovis Metropolitan Area of California, contextual interviews and focus group interviews with a homeowner sub-sample, we find evidence of an interplay of social-structural, institutional, and cultural factors involved in influencing individual water use behaviors and landscape decision making. The complexity of residential behaviors and decision-making poses some potential issues with regards to the interactions between individual households and institutional actors in matters of water usage and landscaping, as survey respondents indicate relatively little confidence in institutions and groups to make wise water policy decisions. We conclude that the promotion and implementation of sustainable water use practices will require not only environmental education for the citizenry, but also a tailoring of information for environmental educational initiatives that address the particularities of individual neighborhoods and communities.

Oral cancer cells (TYS) and the signalling pathways involved in metastasis, in response to cancer-associated fibroblasts (CAFs, COM) and normal oral mucosal fibroblasts (MM1) was studied. Metastatic cell behaviour was observed by cell-scatter, 3D-collagen gel migration and 3D-spheroid invasion assays. Akt, MAPK, EGFR, TGFβRii and CXCR4 inhibitors were used to identify the signalling pathways involved. Signalling pathway protein expression and activation were assessed by SDS-PAGE and Western Blotting. COM-CM (conditioned medium) and MM1-CM stimulated cancer cell scattering, which was blocked only by the Akt inhibitor. COM-CM induced scattered cancer cells showed higher levels of Akt phosphorylation than the negative control and MM1-CM. Migration and invasion of TYS cells into the collagen gels from the spheroids was stimulated by CM from both sources, compared to the negative control. COM cells stimulated TYS, cancer cell invasion into the collagen more than MM1 and the control. Akt and EGFR inhibitors effectively blocked CM and COM cell-induced invasion. Akt-silenced cancer cells were not stimulated to migrate and invade by fibroblast-CM and did not survive addition of the EGFR inhibitor. This suggests that CAFs stimulate oral cancer cell migration and invasion in an Akt- dependent manner. EGFR and Akt are potential therapy targets in metastatic oral cancer.

Visits to coastal and inland-waterways have strong associations with many health and economic benefits but are also opportunities for exposure to environmental pollution. In England, few balanced survey samples exist which can facilitate accurate identification of correlates with recreation in blue spaces. This information could support risk assessment for likelihood of exposure and message targeting in case of environmental threats. We process data from a recent (2022-2023) and large (n = 177,551) survey of English residents to describe demographic, seasonal and regional correlates with any participation in water-based recreational activities in previous year (logistic regression model), and in the previous 28 days (zero-inflated negative binomial regression). Activities studied were: surfing and paddleboarding; open water swimming; scuba-diving and snorkelling; canoeing and kayaking; angling. Summer was associated with most frequent participation, winter with fewest sessions except for rowing. Anglers were group most likely to be socially vulnerable: less likely to be university educated, more likely to be disabled and especially likely to be male. People resident in rural locations were more likely to participate at least once in prior year, but did not have higher participation rates in the previous 28 days. Regional variations in specific activities may suggest where demand for water recreation is unmet. The results provide a reference description of outdoor water-recreationalists doing specific types of activity in England and may be useful when designing emergency messages and otherwise setting policy with regard to management of microbiological, radiological or chemical hazards in coastal and inland waters.

The overwhelming evidence supports the assertion that the climate is undergoing change. Understanding the perception of locals of the magnitude of climate change and its influence on non-timber forest products (NTFPs) challenge at a global scale. Although studies on climate change, value addition, and the multiple uses of NTFPs and their impact on local livelihoods have been conducted, locals' perceptions of these factors have not been fully explored. This study aims to assess various social factors, including education, gender, and religion, and their influence on locals' perceptions of the abovementioned factors. The research focused on five regions where NTFPs are prevalent in Ghana (Western North, Bono, Ahafo, Ashanti, and Eastern regions). To investigate the impact of social factors on local perceptions of climate change, value addition, and the multiple values of NTFPs within rural communities, a total of 732 interviews with a team of interviewers across these five regions in Ghana were carried out. We applied a logistic regression model to assess the social factors and their influencing locals’ perceptions of the mentioned variables. It was revealed that age, gender, education, and occupation did not significantly influence locals' perceptions of climate change. However, religion was found to influence locals' perceptions of climate change. Furthermore, the results demonstrated that gender (P<0.000328) and education (P<0.00426) strongly influenced locals' perceptions of value addition to NTFPs. In contrast, religion and constraints (related to time, finance, and skills) did not significantly influence locals' perceptions. Additionally, it was observed that gender (0.00132), education (0.00692), and religion (8.12e-05) significantly influenced how locals perceive and use NTFPs. In conclusion, this study provides valuable insights into the intricate interplay among local perceptions, climate change, value addition, multiple uses of NTFPs, and the capacity of NTFPs to enhance the well-being of forest fringe communities. These findings underscore the importance of comprehensive, tailor-made interventions that consider local perspectives and adhere to sustainable approaches, with the aim of optimising the positive impacts of NTFPs in poverty alleviation and overall community development.

Manipulation of the intestinal microbiome is an emerging area of research, especially in hind-gut fermenters such as the horse. The aim of this study was to determine whether fecal pH can provide a simple and cost-effective tool to document changes in the intestinal metabolome and microbiome following supplementation of feed with an enzyme rich malt extract (ERME). Fecal pH was determined weekly in triplicate using a commercial soil pH meter in 72 Thoroughbred racehorses in training before and during supplementation with ERME (300mls per day divided into two feeds) alongside their regular feeding schedule. No control group was included. Fecal pH increased over the 4 weeks of treatment from 6.20 (6.15-6.24) to 6.40 (6.38-6.44; P&lt;0.0001). Changes were not observed at one-week intervals but were apparent after 2 weeks There was a significant increase in the proportion of horses with a ‘normal’ pH at the end of the study (55%) compared to the start of the study (11%; p&lt;0.001). These data support the further validation of the use of fecal pH in large scale microbiome/metabolome studies in the horse, although comparisons with these outcomes are now warranted.

This paper studies the combined effect of corrosion and fatigue on the growth of cracks in aircraft and on the effect of skin corrosion and stress corrosion cracking on the load bearing capacity of rib stiffened aircraft wings. In this context it is shown that the growth of cracks from surface pitting, and also from intergranular cracking at a fastener hole, can be accurately computed using the Hartman-Schijve variant of the NASGRO crack growth equation. The examples studied support the lead crack approach, that has been independently developed by the USAF and the Australian Defence Science Technology Group, in which the growth of lead cracks is often exponential. In the case of skin corrosion it is shown that to be consistent with the US Joint Service Structural Guidelines (JSSG2006) assessment of its effect on the load bearing capacity of the wing should involve an assessment of whether at 115% DLL the remaining material exceeds the yield stress of the material.

Sex differences are essential factors in disease etiology and manifestation in many diseases such as cardiovascular disease, cancer, and neurodegeneration (1). The biological influence of sex differences (including genomic, epigenetic, hormonal, immunological, and metabolic differences between males and females) and the lack of biomedical studies considering sex differences in their study design has led to several policies. For example, the National Institute of Health’s (NIH) sex as a biological variable (SABV) and Sex and Gender Equity in Research (SAGER)) policies to motivate researchers to consider sex differences (2). However, drug repurposing, a promising alternative to traditional drug discovery by identifying novel uses for FDA-approved drugs, lacks sex-aware methods that can improve the identification of drugs that have sex-specific responses (1,3–5). Sex-aware drug repurposing methods either select drug candidates that are more efficacious in one sex or deprioritize drug candidates based on if they are predicted to cause a sex-bias adverse event (SBAE), unintended therapeutic effects that are more likely to occur in one sex. Computational drug repurposing methods are encouraging approaches to develop for sex-aware drug repurposing because they can prioritize sex-specific drug candidates or SBAEs at lower cost and time than traditional drug discovery. Sex-aware methods currently exist for clinical, genomic, and transcriptomic information (3,6,7). They have not expanded to other data types, such as DNA variation, which has been beneficial in other drug repurposing methods that do not consider sex (8). Additionally, some sex-aware methods suffer from poorer performance because a disproportionate number of male and female samples are available to train computational methods (3). However, there is development potential for several different categories (i.e., data mining, ligand binding predictions, molecular associations, and networks). Low-dimensional representations of molecular association and network approaches are also especially promising candidates for future sex-aware drug repurposing methodologies because they reduce the multiple hypothesis testing burden and capture sex-specific variation better than the other methods (9,10). Here we review how sex influences drug response, the current state of drug repurposing including with respect to sex-bias drug response, and how model organism study design choices influence drug repurposing validation.

We have performed the first comparative analysis of the potential of two physiologically-diverse model cyanobacteria, Synechococcus PCC 7002 (S.7002) and Synechococcus PCC 7942 (S.7942), for the photosynthetic production of four chemically-different high-value terpenes: two monoterpenes limonene and pinene, and two sesquiterpenes bisabolene and farnesene. We showed, for the first time, that S.7002 and S.7942 can produce farnesene and bisabolene, respectively. Both cyanobac-teria produced farnesene (S.7942 better than S.7002) more efficiently than the other tested terpenes (especially pinene the weakest produced terpene). S.7002 produced limonene better than bisabo-lene, whereas S.7942 produced bisabolene better than limonene. These findings suggest that S.7942 is better suited to produce sesquiterpenes than monoterpenes. Also interestingly, higher levels of terpenes were produced by S.7942 and S.7002 expressing a terpene-synthase gene from both a RSF1010-derived replicating plasmid and a neutral chromosomal site, as compared to ei-ther the plasmid alone or the chromosome alone. These results suggest that in both cyanobacteria the production of terpenes is more limited by the activity of terpene synthases than the abondance of terpene precursors. Finally, higher levels of terpenes were produced by S.7002 growing on urea (a frequent pollutant) as compared to nitrate (or ammonium) the standard nitrogen sources for cyanobacteria (more expensive than urea).

Using the nematode C. elegans germline as a model system, we previously reported that PUF-8 (a PUF RNA-binding protein) and LIP-1 (a dual-specificity phosphatase) repress sperm fate at 20°C and the dedifferentiation of spermatocytes into mitotic cells (termed "spermatocyte dedifferentiation") at 25°C. Thus, double mutants lacking both PUF-8 and LIP-1 produce excess sperm at 20°C, and their spermatocytes return to mitotically dividing cells via dedifferentiation at 25°C, resulting in germline tumors. To gain insight into the molecular competence for spermatocyte dedifferentiation, we compared the germline phenotypes of three mutant strains – fem-3(q20gf), puf-8(q725; fem-3(q20gf), and puf-8(q725); lip-1(zh15). Both fem-3(q20gf) and puf-8(q725); fem-3(q20gf) mutants produced excess sperm like puf-8(q725); lip-1(zh15) double mutants. Our results show that spermatocyte dedifferentiation was not observed in fem-3(q20gf) mutants, but it was more aggressive in puf-8(q725); lip-1(zh15) than in puf-8(q725); fem-3(q20gf) mutants. These results suggest that MPK-1 (the C. elegans ERK1/2 MAPK ortholog) activation by removing the function of LIP-1 in the absence of PUF-8 promotes spermatocyte dedifferentiation. This idea was confirmed using Resveratrol (RSV), a potential activator of MPK-1 and ERK1/2 in C. elegans and human cells. Notably, spermatocyte dedifferentiation was significantly enhanced by RSV treatment, and its effect was blocked by mpk-1 RNAi. We, therefore, conclude that PUF-8 and MPK-1 are normally required to inhibit spermatocyte dedifferentiation and tumorigenesis. Since these regulators are broadly conserved, we suggest that similar regulatory circuitry may control cellular dedifferentiation and tumorigenesis in other organisms, including humans.

(1) Background: Premature infants require mothers’ milk fortification to meet nutrition needs, but breast milk composition may be variable leading to a risk of inadequate nutrition. We aimed at determining factors influencing mothers’ milk macronutrients. (2) Methods: Milk samples were analyzed for the first 5 weeks after premature delivery, by infrared spectroscopy. Mothers’ nutritional intake data were obtained during standardized interviews with dieticians then analyzed with reference software. (3) Results: Composition of 367 milk samples from 81 mothers was (Median [range]g/100mL): Carbohydrates 6.8[4.4-7.3], lipids 3.4[1.3-6.4], proteins 1.3[0.1-3.1]. There was a relationship of milk composition with mothers’ carbohydrates intake only (r=0.164; p<.01). Postnatal age was correlated with milk proteins (r=-0.505 p<.001) & carbohydrates (r=+0.202, p<.001). Multiple linear regression analyses showed (coefficient) a relationship between milk proteins r=0.547 and postnatal age (-0.028), carbohydrates intake (+0.449) and the absence of maturation (-0.066); and between milk lipids r=0.295 and carbohydrates intake (+1.279) and smoking (-0.557). Finally, between milk carbohydrates concentration r=0.266 and postnatal age (+0.012) and smoking (-0.167). (4) Conclusions: Variability of mothers’ milk composition is differentially associated for each macronutrient with maternal carbohydrates intake, antenatal steroids, smoking, and postnatal age. Improvement in milk composition could be achieved by modification of these related factors.

We develop an optimized force-field for poly(3-hexylthiophene) (P3HT) and demonstrate its utility for predicting thermodynamic self-assembly. In particular, we consider short oligomer chains, model electrostatics and solvent implicitly, and coarsely model solvent evaporation. We quantify the performance of our model to determine what the optimal system sizes are for exploring self-assembly at combinations of state variables. We perform molecular dynamics simulations to predict the self-assembly of P3HT at ~350 combinations of temperature and solvent quality. Our structural calculations predict that the highest degrees of order are obtained with good solvents just below the melting temperature. We find our model produces the most accurate structural predictions to date, as measured by agreement with grazing incident X-ray scattering experiments.

A clinical simulation web-based program, known as FIRST2ACT (Feedback Incorporating Review and Simulation Techniques to Act on Clinical Trends) is designed to increase the efficacy of cli-nicians’ actions in the recognition and immediate response to a patient’s deterioration. This study, which was nested in a larger mixed method project, used ten focus groups (n=65) of graduate, enrolled, registered nurses, Associate Nurse Unit Managers, and general manag-ers/educators/coordinators from four different institutions to investigate whether nurses felt their practice was influenced by participating in either a face-to-face or web-based simulation educa-tional programme about patient deterioration. Results indicate individuals who were less ‘tech-savvy’ appreciated the flexibility of web-based learning, which increased their confidence. Face-to-face students appreciated self-reflection through performance evaluation. While face-to-face simulations were unable to completely duplicate symptoms, they did show nurses' adaptability. Both interventions enhanced clinical practice by improving documentation and re-plies while also boosting confidence and competence. Web learners initially experienced tech-related anxiety, which gradually subsided, demonstrating healthcare professionals' resilience to new learning approaches. Overall, the study highlighted the advantages and challenges of web-based and face-to-face education in clinical practice, emphasising the importance of adapta-bility and reflective learning for healthcare professionals. Further exploration of specific topics is required to improve practice, encourage knowledge sharing among colleagues, and improve early detection of patient deterioration.

Weight loss solutions are on the rise, and there is growing interest in natural alternatives to the pharmaceuticals in the market, which are not devoid of relevant side effects. To this end, the objective of the current study is to assess the effects of a botanical-based blend comprised of lemon verbena and hibiscus extracts in weight management, body fat, appetite, lipid, and glucose profiles, in an overweight population, for 90 days. As a result, the volunteers presented significant weight loss in absence of diet, which coincided with decreased body fat. Body fat was assessed by anthropometry, electrical bioimpedance and DEXA scan. Cholesterol levels were also significantly decreased. Satiety assessment revealed that the product contributed to increased feeling of fullness and satisfaction after a meal, compared to the placebo group, which could contribute to the weight loss observed. Blood glucose and blood pressure levels remained unchanged, which was expected as the volunteers were normoglycemic and their blood pressure was in the healthy range. In conclusion, daily supplementation of a botanical-based blend contributes to weight loss in overweight individuals, in absence of diet, while not affecting other parameters that are in the healthy range. This product could be a candidate alternative or add-on to other weight loss products, as part of a healthy lifestyle.

Dysregulation of high-frequency neuronal oscillations has been implicated in the pathophysiology of schizophrenia. Chronic methamphetamine (METH) use can induce psychosis similar to paranoid schizophrenia. The current study in mice aimed to determine the effect of chronic METH treatment on ongoing and evoked neuronal oscillations. C57BL/6 mice were treated with METH or vehicle control for three weeks and implanted with extradural recording electrodes. Two weeks after the last METH injection, mice underwent three EEG recording sessions to measure ongoing and auditory-evoked gamma and beta oscillatory power in response to an acute challenge with METH (2mg/kg), the NMDA receptor antagonist MK-801 (0.3mg/kg), or saline control. A separate group of mice pretreated with METH showed significantly greater locomotor hyperactivity to an acute METH challenge, confirming long-term sensitisation. Chronic METH did not affect ongoing or evoked gamma or beta power. Acute MK-801 challenge reduced ongoing beta power whereas acute METH challenge significantly increased ongoing gamma power. Both MK-801 and METH challenge suppressed evoked gamma power. Chronic METH treatment did not modulate these acute drug effects. There were minor effects of chronic METH and acute METH and MK-801 on selected components of event-related potential (ERP) waves. In conclusion, chronic METH treatment did not exert neuroplastic effects on the regulation of cortical gamma oscillations in a manner consistent with schizophrenia, despite causing behavioural sensitisation.

A complete model was developed to simulate the behavior of a circular clamped axisymmetric fluid-coupled Piezoelectric Micromachined Ultrasonic Transducer (PMUT). Combining Finite Difference and Boundary Element Matrix (FD-BEM), this model is based on the discretization of the partial differential equation used to translate the mechanical behavior of a PMUT. In the model, both the axial and the transverse displacements are preserved in the equation of motion and used to properly define the neutral line position. To introduce fluid coupling, a Green’s function dedicated to axisymmetric circular radiating sources is employed. The resolution of the behavioral equations is used to establish the equivalent electroacoustic circuit of a PMUT that preserves the average particular velocity, the mechanical power, and the acoustic power. Particular consideration is given to verifying the validity of certain assumptions that are usually made across various steps of previously reported analytical models. In this framework, the advantages of the membrane discretization performed in the FD-BEM model are highlighted through accurate simulations of the first vibration mode and especially the cutoff frequency that many other models do not predict. This high cutoff frequency corresponds to cases where the spatial average velocity of the plate is null and is of great importance for PMUT design because it defines the upper limit above which the device is considered to be mechanically blocked. These modeling results are compared with electrical and dynamic membrane displacement measurements of AlN-based PMUTs in air and fluid. This complete PMUT model using the FD-BEM approach is shown to be very efficient in terms of computation time and accuracy.

The needs for environmental reporting to include positive outcomes considering differences between creation of less harm, benefits and net benefits are explored. To become mainstream, nature-positive development needs positive messaging, measures and metrics to guide, plan and assess urban outcomes. With the accelerating climate crisis and negative messages getting the upper-hand, it’s important to avoid paralysis by bad news. Whilst striving for a nature-positive world, more effort should be on moving beyond zero to qualify and quantify benefits, gains, and regenerative outcomes instead of oscillating around damage and loss sticking points. Life Cycle Benefit Assessment (LCBA) is a method to measure gains in accelerating restoration and climate security. It enables a good news focus as its reach is to quantify and show positive gains beyond the negative and zero loss outcomes. The paper aims to clarify concepts, challenges and quantitative methods then review real-world third-party-certified case studies. Climate security, human wellness and resource viability gains inside safe operating space within planetary boundaries are quantified as positive benefits. Contrary to conventional Life Cycle Impact Assessment (LCIA) LCBA assigns damage and loss as negative debts and benefit as positive gains. It concludes that LCBA offers business and design a new environment assessment tool, with research needed on economic and other outcomes.