Background: The use of technology in paediatrics is increasing, and new health technology will change the way in which paediatric care is delivered in the future. This review is part of the Royal College of Paediatrics and Child Health Paediatrics 2040 project, which is developing a credible vision for the future of paediatrics in the UK. Aims: To summarise the impact of health technology on the delivery of paediatric care over the last ten years. To learn from existing technology use and make recommendations for future implementation. Methods: A search strategy was developed and two databases (Cochrane Library and PubMed) were systematically searched in August 2019 for relevant publications in English. Searches were limited to papers published between January 2009 and August 2019 (with further rapid review of papers published between September 2019 and November 2020). We included papers that studied young people up to the age of 24 or on those providing care for this population. A thematic synthesis of the data from the included studies was undertaken using seven domains of paediatric care. Results: 128 studies were included, grouped by domain of care. Most included studies were defined as digital (n=55) or communication (n=37). Studies looked at the different types of health technology used within different domains of care, including secondary and tertiary care (n=39), public health and prevention (n=29), and community (n=20). Studies were assessed on delivery of care outcomes using positive, negative, mixed and no effect. The most common outcomes reported were adherence and satisfaction. Discussion: This review highlights the growing importance of technology in delivering paediatric care. Six themes emerged: the importance of clear guidelines, continuity of care, confidentiality and privacy, digital poverty, using a personalised approach, and using technology to supplement rather than replace. In future, technology development should involve the end user throughout the design process.

Stream chemistry effectively integrates watershed ecosystem processes on both spatial and temporal scales. Streams of coastal areas integrate a more homogeneous, flat topography wherein there can be interactions between the stream and the body of water into which it drains, especially where tidal fluxes occur. The present study assessed water quality of Thompson Bayou, which comes to the campus of the University of West Florida in a wetland after flowing through 4 km of commercial and private property with associated impacts on water quality. Sampling was carried out for one year at eight discrete sites along Thompson Bayou from the UWF campus to the Escambia River. We used a portable field meter to measure temperature, pH, dissolved O2 (DO), and specific conductivity (SC). Except for temperature, all variables exhibited a spatial pattern of significant variation with distance, with consistent increases in DO and SC as the stream approached the river. These variables also exhibited a temporal pattern of significant seasonal variation, including—and especially—temperature. Data suggest that spatial and temporal patterns of water quality of Thompson Bayou are determined by (1) processing of water by the wetland, (2) interactions of the stream channel with upland forest stands, and (3) the tidal hydrology of the Escambia River.

The group III two-component hybrid histidine kinase MoHik1p in the filamentous fungus Magnaporthe oryzae is known to be a sensor for external osmotic stress and essential for the fungicidal activity of the phenylpyrrole fludioxonil. The mode of action of fludioxonil has not yet been completely clarified but rather assumed to hyperactivate the high osmolarity glycerol (HOG) signaling pathway. To date, not much is known about the detailed molecular mechanism of how osmotic stress is detected or fungicidal activity is initiated within the HOG pathway. The molecular mechanism of signaling was studied using a mutant strain in which the HisKA signaling domain was modified by an amino acid change of histidine H736 to alanine A736. We found that MoHik1pH736A is as resistant to fludioxonil but not as sensitive to osmotic stress as the null mutant ∆Mohik1. H736 is required for fludioxonil action but is not essential for sensing sorbitol stress. Consequently, this report provides evidence of the difference in the molecular mechanism of fludioxonil action and the perception of osmotic stress. This is an excellent basis to understand the successful phenylpyrrole-fungicides’ mode of action better and will give new ideas to decipher cellular signaling mechanisms.

Tubulin superfamily (TSF) proteins are widespread and known for multifaceted roles as cytoskeletal proteins underpinning many basic cellular functions including morphogenesis, division, and motility. In eukaryotes, tubulin assembles into microtubules, a major component of the dynamic cytoskeletal network of fibres, whereas the bacterial homolog FtsZ assembles the division ring at midcell. Functions of the lesser-known archaeal TSF proteins are beginning to be identified, and show surprising diversity, including homologs of tubulin and FtsZ, and a third archaea-specific family, CetZ, implicated in the regulation of cell shape and possibly other unknown functions. In this study, we defined sequence and structural characteristics of the CetZ family and CetZ1 and CetZ2 subfamilies, identified CetZ groups and diversity amongst archaea, and identified potential functional relationships through analysis of the genomic neighbourhoods of cetZ genes. At least three subfamilies of orthologous CetZ proteins were identified in the archaeal class Halobacteria, including CetZ1 and CetZ2 and a novel uncharacterized subfamily. CetZ1 and CetZ2 were correlated to one another and to cell shape and motility phenotypes across diverse Halobacteria. Amongst other known CetZ clusters in orders Archaeoglobales, Methanomicrobiales, Methanosarcinales, and Thermococcales, an additional uncharacterized group from Archaeoglobales and Methanomicrobiales affiliated strongly with Halobacteria CetZs, suggesting they originated via horizontal transfer. Subgroups of Halobacteria CetZ2 and Thermococcales CetZ genes were found adjacent to different type IV pili regulons, suggesting a potential utilization of CetZs by type IV systems. More broadly conserved cetZ gene neighbourhoods included nucleotide and cofactor biosynthesis (e.g., F420) and predicted cell surface sugar epimerase genes. The findings imply that CetZ subfamilies are involved in multiple functions linked to the cell surface, biosynthesis and motility.

This paper examines the importance of choice of cooking fuels in wellbeing, analysing relationships between the proportion of population with primary reliance on different types of fuels for cooking (predictor variable), and key wellbeing indices (outcome variables) - Personal Health, Social Life, Civic Engagement, Life Evaluation, Negative Experience. By combining two global datasets from Gallup and WHO, the study adds to current evidence by taking a global perspective. Controlling for demographic factors such as income per capita, age, education level, employment, etc., regression modelling of these relationships show that clean cooking fuels are influential in all of the key wellbeing indices with the exception of the Life Evaluation Index. Among the key wellbeing indices, Personal Health and Negative Experience Indices are the most strongly influenced by choice of clean cooking fuels. By adding access to electricity as an additional predictor variable, the analysis highlights the potential for integrating eCooking into national electrification plans as part of sustainable energy transitions, given that health outcomes (Personal health and Negative experience indices) appear to be as closely linked to choice of cooking fuels as to access to electricity.

Satellite-based broad-scale (i.e., global and continental) human settlement data offer foundational information for diverse applications spanning climate hazard mitigation, sustainable development monitoring, spatial epidemiology, and demographic modeling. While many human settlement products report exceptional detection accuracies above 85%, there is a substantial blind spot in that product validation is typically centered on large urban areas rather than rural, small-scale settlements that are home to 3.4 billion people. In this study, we make use of a data-rich collection of 30 refugee settlements in Uganda to produce a targeted assessment of small-scale settlement detection by four broad-scale human settlement products: Global Human Settlements Built-Up Sentinel-2 (GHS-BUILT-S2), World Settlement Footprint (WSF), High Resolution Settlement Layer (HRSL), and Geo-Referenced Infrastructure and Demographic Data for Development (GRID3). We measured each product’s areal coverage within refugee settlements, assessed product detection accuracies in comparison to an independent dataset of 317,416 refugee settlement building footprints, and examined agreement between products. For refugee settlements established before 2016, the human settlement products had a low median F1-Score (F1) of 0.24, a high median false alarm rate of 0.59, and tended to only agree at locations of highest building density. Individually, WSF entirely overlooked 8 of the 30 study refugee settlements (median F1=0.17); GHS-BUILT-S2 underestimated the building footprint area by a median 50% (F1=0.15); GRID3 overestimated the building footprint area by a median 280% (F1=0.38); and HRSL underestimated the median area by 7% (F1=0.34). All products suffer from low detection accuracy and high false alarm rates, but GRID3 and HRSL, based on 0.5 meter resolution imagery, offer better detection accuracy than GHS-BUILT S2 and WSF, which are based on 10-30 meter resolution imagery. These results show that human settlement products have far to go in providing an accurate depiction of small-scale refugee settlements and would benefit from incorporating refugee settlements in training and validation of broad-scale human settlement detection.

The accurate quantification of $\frac{F{e}^{3+}}{\Sigma Fe}$ ratios for Mössbauer spectroscopic room temperature measurements involves many steps and, when shown in a composite Mössbaur data table, does not allow enough space for more Mössbauer parameters to be presented in the composite table. So a simple formula is derived, (presented as a short communication) which users will find helpful when they have to determine corrected $\frac{F{e}^{3+}}{\Sigma Fe}$ ratios in their room temperature Mössbauer experiments.

Background: Articles published in scholarly journals form part of the scientific evidence base. It is the responsibility of the scientific community to maintain its integrity. In 2011 the BMJ commissioned a feature article to draw attention to an article that had appeared in another journal- The Lancet 13 years previously. The Lancet had already retracted the article. These actions exemplify the best traditions of scientific record-keeping. Objective: This submission examines whether the main claims summary made in the BMJ were factual. Method: We examine what was published in the Lancet against what was published in the BMJ and verify against the findings in the GMC hearings transcripts and verdict of the UK High Court. Results: The 6 points highlighted in BMJ had errors and need to be corrected. Conclusions: There are significant differences between what was reported in the Lancet paper and what was alleged to be there by the BMJ. This article aims only to point to errors in the BMJ article, to set the record straight. It does not show there was a causal association between MMR vaccination and autism.

Biochemical signaling is the key mechanism to coordinate a living organism in all aspects of its life. It is still enigmatic how exactly cells and organisms deal with environmental signals and irritations precisely because of the limited number of signaling proteins and a multitude of transitions inside and outside the cell. Many components of signaling pathways are functionally pleiotropic, which means they have several functions. A single stimulus often activates multiple effectors, a distinct effector can be activated by numerous stimuli and signals triggered by different stimuli are often transduced via shared network components. This very compact and concise review sheds light on the most important molecular mechanisms of cellular signaling in fungi.

The past years saw the rise of genomic biobanks and mega-scale meta-analysis of genomic data that promise to reveal the genetic underpinnings of health and disease. However, the over-representation of Europeans in genomic studies not only limit the global understanding of disease risk and intervention efficacy, but also inhibit viable research into the genomic differences between carriers and patients. Whilst the community has agreed that more diverse samples are required, it is not enough to blindly increase diversity; the diversity must be quantified, compared, and annotated to lead to insight. Genetic annotations from separate biobanks need to be comparable, computable, operate without access to raw data due to privacy concerns. But they must be comparable, both for regular research and to allow international comparison in response to pandemics. Here, we evaluate the appropriateness of commonly used genomic tools used to depict population structure in a standardized and comparable manner. The end goal is to reduce the effects of confounding and learn from genuine variation in genetic effects on phenotypes across populations, which will improve the value of biobanks, locally and internationally, increase the accuracy of association analyses, and inform developmental efforts.

Air pollution has created a lot of problems in the developed and developing countries. To avoid or reduce these problems, constant monitoring of the air should be ensured. The conventional techniques is costly because it requires a lot of money and time consuming. Biomonitoring has been the alternative method. Moss, lichens and plants are biomonitors available to entrap air pollutants. The aim of this paper is to discuss one of the ways of monitoring air pollution – Moss bag technique. To do this, types, choice, preparation, handling of bags after preparation of moss were discussed. From the literatures consulted, it was discovered that there were differences in the techniques used by the researchers. In all, the use of mosses with emphasis on the employment of moss bag have proved to be a powerful tool in airborne particulate and toxic elements. To conclude, developing countries should focus more on this technique because it will reduce cost of air monitoring.

Reconstructing the Tree of Life remains a central goal in biology. Early methods, relying on small numbers of morphological or genetic characters, often yielded conflicting evolutionary histories, undermining confidence in the results. Investigations based on phylogenomics, which use hundreds to thousands of loci for phylogenetic inquiry, have provided a clearer picture of life's history, but certain branches remain problematic. To resolve difficult nodes on the Tree of Life, two recent studies tested the utility of synteny, the conserved collinearity of orthologous genetic loci in two or more organisms, for phylogenetics. Synteny exhibits compelling phylogenomic potential while also raising new challenges. We identify and discuss specific opportunities and challenges that bear on the value of synteny data and other rare genomic changes for phylogenomic studies. Synteny-based analyses of highly contiguous genome assemblies mark a new chapter in the phylogenomic era and the quest to reconstruct the Tree of Life.

Chronic myeloid leukemia (CML) is the most common form of leukemia in adults and accounts for approximately 15% of all leukemia cases. The etiology of this disease is based on the presence of the oncogenic Bcr/Abl fusion protein, which has dysregulated tyrosine kinase activity. This pathological condition is the result of a chromosomal translocation between chromosomes 9 and 22 leading to the formation of the Philadelphia chromosome (Ph). Clinical establishment of targeted therapy with Abl kinase inhibitors (AKIs) has been observed in the treatment of CML. Therapy resistance in patients with CML is due to genetic alterations in the cells of CML, specifically affecting the Bcr/Abl oncoprotein. Acquired resistance of CML patients to tyrosine kinase inhibitors (AKIs) has also been associated with the tumor microenvironment (TME). This study aimed to examine the role of hypoxic conditions in the development of chemoresistance to certain AKIs in CML. The findings of our study indicate that exposure to hypoxic conditions leads to a substantial increase in chemoresistance to crizotinib, while only resulting in a slight increase in chemoresistance to imatinib. It is worth noting that both drugs effectively block Bcr/Abl function. Furthermore, it was observed that the inclusion of the JAK1/2 inhibitor ruxolitinib resulted in an augmentation of chemoresistance to crizotinib in the context of hypoxia. Overexpression of hypoxia-inducible factor 1a (HIF1a) and silencing of JAK2 confirmed that the two proteins cooperate in mediating chemoresistance to crizotinib in CML cell lines. It is noteworthy that the compound 2-methoxy estradiol (2ME2), which is a metabolite of estradiol lacking estrogenic activity, has shown efficacy in reinstating the sensitivity of CML cells to crizotinib in the presence of hypoxic circumstances. Additionally, when used in conjunction with a JAK2 inhibitor, 2ME2 exhibited activity in restoring crizotinib sensitivity in CML cells. The findings of our study underscore the significance of selectively targeting elements of the HIF1α pathway in order to achieve total eradication of chronic myeloid leukemia (CML) cells.

The ability to replicate scientific experiments is a cornerstone of the scientific method. Sharing ideas, workflows, data, and protocols facilitates testing the generalizability of results, increases the speed that science progresses, and enhances quality control of published work. Fields of science such as medicine, the social sciences, and the physical sciences have embraced practices designed to increase replicability. Granting agencies, for example, may require data management plans and journals may require data and code availability statements along with the deposition of data and code in publicly available repositories. While many tools commonly used in replicable workflows such as distributed version control systems (e.g. “git”) or scripted programming languages for data cleaning and analysis may have a steep learning curve, their adoption can increase individual efficiency and facilitate collaborations both within entomology and across disciplines. The open science movement is developing within the discipline of entomology, but practitioners of these concepts or those desiring to work more collaboratively across disciplines may be unsure where or how to embrace these initiatives. This article is meant to introduce some of the tools entomologists can incorporate into their workflows to increase the replicability and openness of their work. We describe these tools and others, recommend additional resources for learning more about these tools, and discuss the benefits to both individuals and the scientific community and potential drawbacks associated with implementing a replicable workflow.

Understanding swash zone dynamics is of crucial importance for coastal management as the swash motion, consisting of the uprush of the wave on the beach face and the subsequent downrush, is responsible for driving changes the beach morphology trough sediment exchanges between the sub-aerial and sub-aqueous beach. Improved understanding of the probabilistic characteristics of these motions has the potential to allow coastal engineers to develop improved sediment transport models which, in turn, can be further developed into coastal management tools. In this paper, novel descriptors of swash motions are obtained by combining field data and statistical modelling. Our results indicate that the probability distribution function (PDF) of shoreline height (p(ζ)) and trough-to-peak swash heights (p(ρ)) measured at a high energy, sandy beach were both inherently multimodal. Based on the observed multimodality of these PDFs, Gaussian Mixtures are shown to be the best method to statistically model them. Further, our results show that both offshore and surf zone dynamics are responsible for driving swash zone dynamics, which indicates unsaturated swash. The novel methods and results developed in this paper, both data collection and analysis, could aid coastal managers to develop improved swash zone models in the future.

Chronological age represents the greatest risk factor for many life-threatening diseases including neurodegeneration, cancer and cardiovascular disease; ageing also increases susceptibility to infectious disease. Current therapies that effectively tackle individual diseases may have little impact on the overall healthspan of older individuals, who would still be vulnerable to other age-related pathologies. However, recent progress in ageing research has highlighted the accumulation of senescent cells with chronological age as a probable underlying cause of pathological ageing. Cellular senescence is an essentially irreversible proliferation arrest mechanism that has important roles in development, wound healing and preventing cancer, but it may limit tissue function and cause widespread inflammation with age. The serine/threonine kinase mTOR is a regulatory nexus heavily implicated in both ageing and senescence. Excitingly, a growing body of research has highlighted rapamycin and other mTOR inhibitors as promising treatments for a broad spectrum of age-related pathologies, including neurodegeneration, cancer, immunosenescence, osteoporosis, rheumatoid arthritis, age-related blindness, diabetic nephropathy, muscular dystrophy, and cardiovascular disease. In this review, we assess the use of mTOR inhibitors to treat age-related pathologies, discuss possible molecular mechanisms of action where evidence is available, and consider strategies to minimize undesirable side effects. We also emphasize the urgent need for reliable, non-invasive biomarkers of senescence and biological ageing to better monitor the efficacy of any healthy ageing therapy.

Accurate determination of the concentration of alcohols and their metabolites is important in forensics and in several life science areas. A new method has been developed to quantify alcohols and their oxidative products using a headspace gas chromatography- mass spectrometer and isotope-labelled internal standards. This work demonstrates the application of this method, specifically in quantifying the concentration of oxidative products of alcohol and other minor alcohols found in hand sanitizers, which have become an essential household item since the COVID-19 pandemic. Apart from the major component, the minor alcohols found in hand sanitizers include methanol, isopropanol, and n-propanol. In ethanol-based hand sanitizers, a significant amount of acetaldehyde was observed as an oxidation product, while in isopropanol-based hand sanitizers, acetone was observed. The concentration of acetaldehyde in ethanol-based hand sanitizers significantly increased with storage time and temperature, whereas no such increase of acetone concentration was observed in isopropanol-based hand sanitizers with storage time and temperature.

The national study analyzes sea level rise (SLR) impacts based on 36 different SLR and storm surge scenarios across 5.7 million geographic locations and 3 time periods. Taking an approach based on engineering design guidelines and current cost estimates, the study details projected cost impacts for states, counties, and cities. These impacts are presented from multiple perspectives including total cost, cost per-capita, and cost per-square mile. The purpose of the study is to identify specific locations where infrastructure is vulnerable to rising sea levels. The study finds that Sea Level Rise (SLR) and minimal storm surge is a $400 billion threat to the United States by 2040 that includes a need for at least 50,000 miles of protective barriers. The research is limited in its scope to protecting coastal infrastructure with sea walls. Additional methods exist and may be appropriate in individual situations. The study is original in that it is a national effort to identify infrastructure that is vulnerable as well as the cost associated with protecting this infrastructure.

Retinoic acid receptor-related orphan receptor γ (RORγ) is a transcription factor regulating the expression of the pro-inflammatory cytokine IL-17 in human T helper 17 (Th17) cells. Activating RORγ can induce multiple IL-17-mediated autoimmune diseases but may also be useful for anticancer therapy. Its deep immunological functions make RORɣ an attractive drug target. Over 100 crystal structures have been published describing atomic interactions between RORɣ and agonists and inverse agonists. In this review, we focus on the role of dynamic properties and plasticity of the RORɣ orthosteric and allosteric binding sites by examining structural information from crystal structures and simulated models. We discuss the possible influences of allosteric ligands on the orthosteric binding site. We find that high structural plasticity favors the druggability of RORɣ, especially for allosteric ligands.

Research rarely explores LGBTQ+ youth bullying in the context of culture-specific outcomes (e.g., LGBTQ+ identity development) and what can mitigate the impact of peer stressors. This study used a concurrent mixed methods design to explore how experiences of peer victimization predicted LGBTQ+ youth’s identity development (i.e., stigma sensitivity, concealment motivation, and difficult process) and whether social support and outness served as protective, moderating factors. The mixed-methods approach provides a culture-specific context via qualitative inquiry to inform whether the quantitative findings align with how youth qualitatively discuss their experience of bullying, negative outcomes, and social support. Our sample consisted of 349 LGBTQ+ youth 14-17 years old who completed a survey (quantitative sample), and a subset of 39 LGBTQ+ youth who completed a semi-structured interview (qualitative sample). Our quantitative findings indicated that greater overall peer victimization was positively related to LGBIS-revised subscales of stigma sensitivity, concealment motivation, and difficult process, where both outness and social support moderated such relations. Qualitatively, victimized youth also reported stigma sensitivity and concealment motivation, while also endorsing how being out and having a support system played a role in their experience of being victimized. These qualitative findings align with our quantitative findings that classmate support mitigated the effects of peer victimization on difficulty of coming out. Implications for practitioners and researchers are provided.

After reviewing foundational literature by Snyder, I will demonstrate how hope theory has been used in psychological interventions and psychiatry, how hope influences learning and medical outcomes, and how hope can be applied to difficult life circumstances. Using this literature review, hope theory will be interrogated. I will argue that hope theory has developed its way through the years to garner many strengths, however a few weaknesses do exist and will be described. I will conclude with recommendations for using hope theory in practice, including the medical field, psychological interventions and counseling, and student development.

A multiscale (micro-macro) approach is proposed for the establishment of the full thermal and induced stress fields in cracked composites that are subjected to heat flow. Both the temperature and stresses distributions are determined by the solution of a boundary value problem with one-way coupling. In the micro level and for combined thermomechanical loading, a micromechanical analysis is employed to determine the effective moduli, coefficients of thermal expansion and thermal conductivities of the undamaged composite. In the macro level, the representative cell method is employed according to which the periodic damaged composite region is reduced, in conjunction with the discrete Fourier transform, to a finite domain problem. As a result, a boundary value problem is obtained in the Fourier transform domain which is appropriately discretized and solved. The inverse transform and an iterative procedure provide the full thermal and stress fields. The proposed method is verified by comparisons with exact solutions. Applications are given for the determination of the thermal and stress fields in cracked fiber-reinforced polymeric composite, cracked porous ceramic material and cracked periodically layered ceramic composite caused by the application of heat flow. The presented formulation admits however the application of a combined mechanical and heat flux on cracked composites.

The dynamic interplay of signaling networks in most major cellular processes is characterized by the orchestration of reversible protein phosphorylation. Consequently, analytic methods like quantitative phospho-peptidomics has been pushed forward from a highly specialized edge-technique to a powerful and versatile platform for comprehensively analyzing the phosphorylation profile of living organisms. Despite enormous progress in instrumentation and bioinformatics, a major problem remains a high number of missing values caused by the experimental procedure due to either a random phospho-peptide enrichment selectivity or borderline signal intensities, which both cause the exclusion for fragmentation using the commonly applied data dependent acquisition (DDA) mode. Consequently, an incomplete dataset reduces confidence in the subsequent statistical bioinformatic processing. Here, we successfully applied data independent acquisition (DIA) by using the filamentous fungus Magnaporthe oryzae as model organism and could prove that while maintaining data quality (such as phosphosite and peptide sequence confidence), the data completeness increases dramatically. Since the method presented here reduces the LC-MS/MS analysis from 3 h to 1 h and increases the number of phoshosites identified up to 10-fold in contrast to published studies in fungi, we pushed the phospho-proteomic technique beyond its current limits and could provide a sophisticated resource for investigation of signaling processes in filamentous fungi.

Geopolymers, made from aluminosilicate raw materials, offer significant environmental advantages over conventional concrete (CC) mixes. This study explores the compressive strength, setting time, and durability of geopolymer concrete (GPC) cylinders, some of which include an additional ordinary portland cement (OPC) mix. Consistent material composition and testing methods are emphasized to achieve reliable results. MATLAB was utilized to develop and assess a neural network model predicting the compressive strength of GPC based on key variables. The model was validated using 16 experimental samples and 1047 samples from various studies. The performance plot displayed the Mean Squared Error (MSE) over iterations, identifying the best training performance at epoch 658 with an MSE of 5.3408. The Error Histogram highlighted distribution errors between predicted and actual compressive strength values, with the highest range from -1.015 to 0.3587, meaning that the predicted values were mostly within a small margin of error from the actual values. This narrow error range indicates that the ANN model has high accuracy in its predictions, as most errors are small and clustered around zero, demonstrating reliable performance in estimating compressive strength. Regression analysis showed varying correlation coefficients (training set R=0.98373, test set R=0.88164, and whole set R=0.96982), indicating adequate predictive accuracy. The results demonstrate that properly trained neural networks can effectively predict the compressive strength of GPC, highlighting its potential as a sustainable construction material.

The energies of spin singlet and triplet bound electron pairs are reckoned for electrons interacting through the Coulomb interaction, while sitting on neigbouring lattice sites. It is concluded that triplet pairs are unlikely to be observed due to screening. The interplay of inter-electron couplings of different spatial range is investigated. High-pressure induced superconductivity is analysed and qualitative agreement is achieved with observed results by working out the dependence of the critical temperature on the microscopic parameters, characterising the electron motion. This approach can be applied to other kinds of inter-electron interactions.

A procedure, dedicated to superconductivity, is extended to study the properties of interacting electrons in normal metals in the thermodynamic limit. Each independent-electron band is shown to split into two correlated-electron bands. Excellent agreement is achieved with Bethe's wave-function for the one-dimensional Hubbard model. The groundstate energy, reckoned for the two-dimensional Hubbard Hamiltonian, is found to be lower than values, obtained thanks to the numerical methods. This analysis applies for any spatial dimension and temperature.

Diversification is an important strategy for managing risk in agricultural systems. Risk analysis can help to support farmers’ diversification strategies, but existing analytical methods are complicated and little used. The minimum regret model helps to fill this gap. It provides a simple, transparent calculation procedure that can be executed with existing spreadsheet software. Regret is an important heuristic in the behavioural sciences and regret-based models are used in finance. The article presents the model with a numerical example. It also presents a framework to compare minimum regret portfolios with two limit cases (maximum utility and minimax regret). A case study illustrates the use of the model and the comparative framework.

This paper presents an experimental scenario aimed at bridging the gap between the cities we have and the cities we need, not only in the 21^st century but also beyond, using the integrated tools of development control and holistic land development model to achieve a planner-led vision of city sustainability. Due to scathing criticisms against the development control system, the paper contends that planners as development approving officers and public interest specialists are better positioned than allied professionals to increase city sustainability through a holistic development process that benefits from the concept of strong sustainability posited by ecological economists. The paper adopts a seven-stage, 56-cell land development matrix (model) to simulate the development of the typical high-rise residential condominium in Ontario, supported with secondary data and the author’s ground experience as a planner and realtor with condominium customer service experience across Toronto and Mississauga cities between 2008 and 2017. Findings reveal that planners can seize the opportunity of being leaders of the development team to synergize the risks and value creation in land development that are key drivers of strong sustainability. The paper suggests some policy implications for averting disasters like fire hazards and terror attacks in high-rise residential buildings.

The current report contributes to the understanding of the stereoselectivity of the chiral dirhodium(II) carboxylate catalysts derived from N-protected amino acid ligands. Investigating the possible effect of ligand stereo-purity on catalyst structure and enantioselectivity was carried out. This was justified through a new X-ray crystal structure for Rh2(S,S,S,R-PTTL)4 diastereomer.

The emergence of CDK4/6 inhibitors, such as palbociclib, ribociclib, and abemaciclib, has revolutionized the treatment landscape for hormone receptor-positive breast cancer. These agents have demonstrated significant clinical benefits in terms of both progression-free survival and overall survival. However, resistance to CDK4/6 inhibitors remains a challenge, limiting their long-term efficacy. Understanding the complex mechanisms driving resistance is crucial for the development of novel therapeutic strategies and improvement of patient outcomes. Translational research efforts, such as preclinical models and biomarker studies, offer valuable insight into resistance mechanisms and may guide the identification of novel combination therapies. This review paper aims to outline the reported mechanisms underlying CDK4/6 inhibitor resistance, drawing insights from both clinical data and translational research in order to help direct the future of treatment for hormone receptor positive metastatic breast cancer.

The rapid growth of network services, Internet of Things devices and online users on the Internet have led to an increase in the amount of data transmitted daily. As more and more information is stored and transmitted on the Internet, cybercriminals are trying to gain access to the information to achieve their goals, whether it is to sell it on the dark web or for other malicious intent. Through thorough literature study relating to the causes and issues that are brought from the security and privacy segment of wireless networks, it is observed that there are various factors that can cause the networks to be an insecure; especially factors that revolve around cybercriminals with their growing expertise and the lack of preparation and efforts to combat them by relevant bodies. The aim of this paper is to showcase major and frequent security as well as privacy issues in wireless networks along with specialized solutions that can assist the related organizations or the public to fathom how great of an impact these challenges can bring if every related stakeholder took a step in reducing them. Through this paper it is discovered that there are many ways these challenges can be mitigated, however, the lack of implementation of privacy and security solutions is still largely present due to the absence of practical application of these solutions by responsible parties in real world scenarios.

Glacial ripping is a newly recognized process sequence in which subglacial erosion is triggered by groundwater overpressure. Investigations in gneiss terrain in lowland Sweden indicate that ripping involves three stages of (i) hydraulic jacking, (ii) rock disruption under subglacial traction and (iii) glacial transport of rock blocks. Evidence for each stage includes, respectively, dilated fractures with sediment fills, disintegrated roches moutonnées and boulder spreads. Here we ask: can glacial ripping also occur in sedimentary rocks, and, if so, what are its effects? The case study area is in hard, thinly bedded, gently dipping Cambrian quartz-arenites at Loch Eriboll, NW Scotland. Field surveys reveal dilated, sediment filled, bedding-parallel fractures, open joints and brecciated zones, interpreted as markers for pervasive, shallow penetration of the quartz-arenite by water at over-pressure. Other features, including disintegrated rock surfaces, boulder spreads and monomict rubble tills, indicate glacial disruption and short distance subglacial transport. The field results, together with published cosmogenic isotope ages, indicate that glacial ripping operated with high impact close to the former ice margin at Loch Eriboll at 17.6-16.5 ka. Glacial ripping thus can operate effectively in bedded, hard sedimentary rocks and the accompanying brecciation is significant – if not dominant - in till formation. Candidate markers for glacial ripping are identified in other sedimentary terrains in former glaciated areas of the Northern Hemisphere.

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

Estrogen receptor-positive (ER+) breast cancer is common among postmenopausal women and is frequently treated with Letrozole. Letrozole inhibits aromatase from synthesizing estrogen from androgens. Decreased estrogen slows the growth of tumors and can be an effective treatment. Letrozole resistance is increasingly being observed, which poses a unique problem for patients. We reanalyzed transcriptomic data comparing individuals who responded to Letrozole therapy (responders) to those who were resistant to treatment (non-responders). We identified SOX11 and S100A9 as two genes that significantly differed between these patients; with “PLK1 signaling events” being the most significant signaling pathway. We also identified PRDX4 and E2F8 as the top transcriptional biomarkers for ER+ treatment resistance. Many of the other significant gene products play a known role in ER+ breast cancer or other types of cancer, which partially validate our results. Several of the gene products we identified do not have a characterized role in ER+ breast cancer. Our analysis identified a set of genes that warrant further research to elucidate the molecular mechanism of Letrozole resistance in this patient population, as well as novel high-performing biomarkers. We anticipate that these findings could contribute to improved therapeutic outcomes in human patients.

Different external stimuli are perceived by multiple sensor histidine kinases and transmitted by phosphorylation via the phosphotransfer protein Ypd1p in the multistep phosphorelay system of the high osmolarity glycerol signaling pathway of filamentous fungi. How the signal propagation takes place is still not known in detail, since multiple sensor histidine kinase genes in most filamentous fungi are coded in the genome, whereas only one gene for Ypd1 exists. That raises the hypothesis that various Ypd1 isoforms are produced from a single gene sequence, perhaps by alternative splicing, facilitating a higher variability in signal transduction. We found that the mRNA of MoYPD1 in the rice blast fungus Magnaporthe oryzae is subjected to an increased structural variation and amplified putative isoforms on a cDNA level. We then generated mutant strains overexpressing these isoforms, purified the products and present here one previously unknown MoYpd1 isoform on a proteome level. Alternative splicing was found to be a valid molecular mechanism to increase the signal diversity in eukaryotic multistep phosphorelay systems.

Antiphospholipid antibody syndrome (APS) is an autoimmune disorder characterised by thrombosis and the presence of antiphospholipid antibodies (aPL): lupus anticoagulant and/or IgG/IgM anti-β2-glycoprotein I and anticardiolipin antibodies. APS carries significant morbidity for a relatively young patient population from recurrent thrombosis in any vascular bed (arterial, venous or microvascular), often despite current standard of care, which is anticoagulation with vitamin K antagonists (VKA). Platelets have established roles in thrombosis at any site, and platelet hyperreactivity is clearly demonstrated in the pathophysiology of APS. Together with excess thrombin generation, platelet activation and aggregation are the common end result of all the pathophysiological pathways leading to thrombosis in APS. However, antiplatelet therapies play little role in APS, reserved as a possible option of low dose aspirin in addition to VKA in arterial or refractory thrombosis. This review outlines the current evidence and mechanisms for excessive platelet activation in APS, how it plays a central role in APS-related thrombosis, what evidence for antiplatelets is available in clinical outcomes studies and potential future avenues to define how to target platelet hyperreactivity better with minimal impact on haemostasis.

The world is currently experiencing COVID-19, one of the worst pandemics that have happened in this century, affecting 10.7 million people worldwide. It has caused massive growth in the number of employees working from home. However, employees have minimal cybersecurity resources unlike organizations with security teams protecting them against attacks. Hence, cybersecurity plays an important role as users can be easily targeted by cybercriminals. This paper examines how cyberattacks have increased during this pandemic and shows how greatly they have affected health organizations, individuals and social networking applications. Results of the attacks include data breaches, false announcements and operations being disrupted. Attacks occurring during this pandemic and how they were handled are also critically discussed. The existing contributions do touch on related attacks but do not provide in-depth solutions regarding the issues. Even though there are many works and findings that were done previously, technology is ever evolving. Therefore, we need to be well versed with current and future issues and provide the latest mechanisms to prevent cybersecurity threats from occurring. On our share, we intend to present our findings on the challenges being faced by the population and its increasing threats as well as presenting unique solutions that can help organizations or related persons understand or spread awareness on the importance of cybersecurity. Through the research performed in this paper, it is found that there are many ways these issues can be alleviated. However, the issue is that there is significant lack of action and investment in terms of actual implementation and application of the available solutions.

This study explores the impact of multi-user interaction, group work, and simulations within virtual worlds on language learning and the development of intergroup empathy. Two distinct research projects were conducted, involving a total of 241 participants aged 19-45. The language learning study engaged 116 participants in diverse interactive experiences, while the intercultural study had 125 participants collaborating in multicultural groups and participating in perspective-taking simulations. Both studies employed qualitative data collection methods, including surveys, interviews, and observations. The findings suggest that the combination of networking strategies, collaborative learning, and simulations within virtual worlds contributes to improvements in learners' language proficiency, confidence, and empathy towards diverse social groups. Participants reported increased motivation and engagement, attributed to the immersive and interactive nature of the virtual environments. The studies highlight the importance of collaboration and reflection in facilitating language acquisition and intercultural understanding. Technical challenges were identified as potential barriers to implementation. The results demonstrate the potential of virtual worlds to enhance language education and foster empathy in diverse societies, offering valuable insights for educators and researchers. However, the findings may be limited by the specific contexts and sample sizes of the studies, warranting further research to explore the generalizability and long-term impact of virtual world interventions. not exaggerate the main conclusions.

The proximal part of the colon offers opportunities to prolong the absorption window following oral administration of a drug. In this work, we used computer simulations to understand how the hydrodynamics in the proximal colon might affect the release from dosage forms designed to target the colon. For this purpose, we developed and compared three different models: a completely-filled colon, a partially-filled colon and a partially-filled colon with a gaseous phase present (gas-liquid model).The highest velocities of the liquid were found in the completely-filled model, which also shows the best mixing profile, defined by the distribution of tracking particles over time. No significant differences with regard to the mixing and velocity profiles were found between the partially-filled model and the gas-liquid model. The fastest transit time of an undissolved tablet was found in the completely-filled model. The velocities of the liquid in the gas-liquid model are slightly higher along the colon than in the partially-filled model. The filling level has an impact on the exsisting shear forces and shear rates, which are decisive factors in the development of new drugs and formulations.

Inflammatory Bowel Disease (IBD) is characterized by chronic remitting and relapsing inflammation of the lower gastrointestinal tract. The etiology underlying IBD remains unknown but is thought to involve a hypersensitive immune response to environmental antigen, including the microbiota. Diagnosis and monitoring of disease is heavily reliant on endoscopy, which is invasive and does not provide information regarding specific mediators. This review describes recent developments in imaging of IBD with a focus on PET and SPECT imaging of inflammatory mediators, and how this may be applied to the microbiota.

This work explores the use of Kuhn verdazyl radicals as building blocks in multifunctional molecular materials in an exemplary study, focusing on the magnetic and the electron transfer (ET) characteristics, but also addressing the question whether chemical modification by cross-coupling is possible. The ET in solution is studied spectroscopically whereas solid state measurements afford information about the magnetic susceptibility or the conductivity of the given samples. The observed results are rationalized based on the chemical structures of the molecules, which have been obtained by X-ray crystallography. The crystallographically observed molecular structures as well as the interpretation based on the spectroscopic and physical measurements are backed up by DFT calculations. The measurements indicate that only weak, antiferromagnetic coupling is observed in Kuhn verdazyls owed to the low tendency to form face-to-face stacks, but also that steric reasons alone are not sufficient to explain this behavior. Furthermore, it is also demonstrated that ET reactions proceed rapidly in verdazyls/verdazylium redox couples and that Kuhn verdazyls are suited as donor molecules in ET reactions.

The Combined Elevation Test (CET) is a musculoskeletal screening technique (MST) replicates the streamline position in swimming and is commonly used in various sports. Although the CET is widely used, no normative data exist within an adolescent population. Therefore, the purpose of this study was to develop a normative data set for the CET within an adolescent population and to evaluate the influence various demographic and anthropometric variables. Data was collected for 416 participants aged between 8 and 18 years old. Age and arm span showed a significant correlation with CET scores (arm span r_s (105) = .478, p = .000, age r_s (416) = .238 p = .000). Regression analysis further quantified the influence of arm span and age on CET scores accounting for 23.1% and 5.3% of variability respectively. These results can be used as a reference point for clinicians and coaches who are using the CET within their assessment.

Fibrosis is a prevalent and detrimental condition associated with various diseases with a high impact on global morbidity and mortality rates. Despite its diverse causes and affected organs, common underlying mechanisms drive the development and progression of the disease. These mechanisms include an exaggerated inflammatory response, excessive activation of fibroblasts, and abnormal tissue remodeling following severe or repetitive tissue injury. Although significant advancements have been achieved to enhance our understanding of fibrosis, there is still a gap between identifying potential antifibrotic targets and successfully translating them into effective clinical interventions. Novel approaches that target specific cellular and molecular processes involved in fibrosis hold promise for reducing the pathological consequences of the disease. Understanding the pathogenesis and clinical implications of fibrotic diseases is crucial for developing effective therapeutic strategies and improving patient outcomes. In this review, we introduce the concept of fibrosis, discuss the mechanisms by which it arises, and explore existing and emerging therapeutic approaches in development.

Citron watermelon (Citrullus lanatus var. citroides) is an underexploited and under-researched crop species with potential to contribute to crop diversification in sub-Saharan Africa and beyond. The species is commonly cultivated in the drier parts of Southern Africa, mainly by smallholder farmers who maintain a wide range of landraces. Understanding the molecular and morpho-physiological basis for drought adaptation of Citron watermelon in these dry environments can aid in screening local germplasm, identification of suitable traits for crop improvement and improving food system resilience among smallholder farmers by adding to crop diversification. This paper reviews literature on drought adaptation of C. lanatus spp. (C3 xerophytes), using the systematic review approach. The review discusses; (i) the potential role of citron watermelon in adding to crop diversification, (ii) alternative food uses and potential by-products that can be processed from citron watermelon and (iii) the role of Sub-Saharan farmers as key actors in conserving citron watermelon germplasm and biodiversity. Finally, the review provides a summary of significant findings and identifies critical knowledge gaps for further research.

We consider an alternative hypothesis of crater formation -- through an electric discharge machining (EDM) of the celestial bodies' surfaces. The source of the energy and the current itself may lie in the plasma infalling on a celestial body (from an extremely strong solar outburst or a nearby supernova). This mechanism may have been even more important than impact cratering in the early Solar System, with potential implications to the history of the dynamics of the System itself and solar activity in particular. In this light, the conclusion that shocked and metamorphosed minerals found within crater sites are evidence of hypervelocity impacts might be reconsidered. There are ambiguities that remain among sources of mineralogical formations. This study is ongoing with details of investigations supporting a new approach to crater formation not yet exhausted. Apart from mineralogical analysis and theoretical considerations regarding the large scale crater formation, we present a description of experimental studies of EDM acting at low pressures. Experimental results are made with crude setups and could easily be replicated on a larger scale with valuable research potential, as there is a well understood relation between the crater size and the energy needed for its production.

After conducting a detailed survey among the villagers of Pallissery and Karukutty, it was observed that in most of the villages the native people have to travel long distances for their basic health needs. Also most of the villagers lack knowledge regarding live health updates. At times, these problems have even resulted in death of many people including pregnant women and children. The objective of our research is to propose an integrated and easy to use Medical Kiosk that can be installed at various locations in rural areas. The Kiosk will provide an integrated environment for all medical related activities and would perform numerous functions like sending notifications regarding medical camps, mobile medical help, important dates for vaccinations, child care, insurance policies and provide other live medical updates to the villagers. It would also support the basic facilities for measurement of body parameters like height, weight, BMI, blood pressure, and heartbeat and also facilitate live consultation facilities with specialized doctors through video and voice chats.

Widely used estimates of food-insecure populations are likely to be biased upwards, lacking adjustment for global increases in sedentary behavior in recent decades. We first construct a household model to account for sedentary choices during leisure and work time decisions. The model rationalizes increasing sedentary behavior from the household by accounting for increasing returns to cognitive human capital vs physical capital, alongside increased productivity of more sedentary activities both at work and at home. The household model then informs an empirical model that makes use of our unique international pseudo-panel data on sitting time, which serves as a proxy for sedentarism. We econometrically estimate a transfer function linking sedentarism to widely available covariates, which then are used to make out-of-sample predictions and can be applied to a large set of countries. The estimated sedentary time can be used to adjust the physical activity level reflected in the minimum dietary energy requirement used to determine a cutoff for food insecurity.

Polyethylene terephthalate (PET) pollution poses significant environmental consequences, and thus new degradation methods must be explored to mitigate this problem. We previously demonstrated that a consortium of three Pseudomonas and two Bacillus species can synergistically degrade PET in culture. The consortium more readily consumes Bis(2-Hydroxyethyl) terephthalate (BHET), a byproduct made in PET depolymerization, compared to PET, and can fully convert BHET into metabolically usable monomers terephthalic acid (TPA) and ethylene glycol (EG). Because of its crystalline structure, the main limitation of the biodegradation of post-consumer PET is the initial transesterification from PET to BHET, depicting the need for the transesterification step in the degradation process. Additionally, there have been numerous studies done on the depolymerization reaction of PET to BHET, yet few have tested the biocompatibility of that product with a bacterial consortium. In this report, a two-step process was implemented for sustainable PET biodegradation, where PET is first depolymerized to form BHET using an Orange Peel Ash (OPA) catalyzed glycolysis reaction, followed by complete degradation of the BHET glycolysis product by the bacterial consortium. Results show that OPA-catalyzed glycolysis reactions can fully depolymerize PET, with an average BHET yield of 92% (w/w) and that the reaction product is biocompatible with the bacterial consortium. After inoculation with the consortium, 19% degradation of the glycolysis product was observed in 2 weeks, for a total degradation percentage of 17% when taking both steps into account. Furthermore, the 10-week total BHET degradation rate was 35%, demonstrating that the glycolysis products are biocompatible with the consortium for longer periods of time, for a total two-step degradation rate of 33% over 10 weeks. While we predict complete degradation is achievable using this method, further experimentation with the consortium can allow for a circular recycling process, where TPA can be recovered from culture media and reused to create new materials.

Knowledge of the spatio-temporal occurrence of avalanche activity is critical for avalanche forecasting and hazard mapping. We present a near-real time automatic avalanche monitoring system that outputs detected avalanche polygons within roughly 10 min after Sentinel- 1 SAR data download. Our avalanche detection algorithm has an average probability of detection of 67.2 % with a false alarm rate averaging 45.9, with maximum POD's over 85 % and minimum FAR's of 24.9 % compared to manual detection of avalanches. The high variability in performance stems from the dynamic nature of snow in the Sentinel-1 data. After tuning parameters of the detection algorithm, we processed five years of Sentinel-1 images acquired over a 150 x 100 km large area in Northern Norway, with the best setup. Compared to a dataset of field-observed avalanches, 77.3 % were manually detectable. Using these manual detections as benchmark, the avalanche detection algorithm achieved an accuracy of 79 % with high POD's in cases of medium to large wet snow avalanches. For the first time, we can present a dataset of spatiotemporal avalanche activity over several winters from a large region. This unique dataset allows for research into the relationship between avalanche activity and triggering meteorological factors, mapping of avalanche prone areas and near-real time avalanche activity monitoring to assist public avalanche forecasting. Currently, the Norwegian Avalanche Warning Service is using our processing system for pre-operational use in three regions in Norway.

Poor soil health is a critical problem in many urban landscapes. Degraded soil restricts plant growth and microorganism activity, limiting the ability of urban landscapes to perform much needed ecosystem services. Incorporation of approximately 33% compost by volume into degraded soil has been proven to improve soil health and structure over time while avoiding the financial and environmental costs of importing soil mixes from elsewhere. However, additions of high volumes of compost could potentially increase the risk of nutrient loss through leaching and runoff. The objective of our study was to consider the effects of different compost amendments on soil health, plant health and susceptibility to nutrient leaching in order to identify ranges of acceptable compost characteristics that could be used for soil remediation in the urban landscape. We conducted a bioassay with Phaseolus vulgaris (Bush Bean) to measure the effect of nine composts from different feedstocks on various plant health parameters. We collected leachate prior to planting to measure nutrient loss from each treatment. We found that all compost amendments improved soil health. Nutrient-rich, manure-based composts produced the greatest plant growth, but also leached high concentrations of nitrate and phosphorus. Some treatments provided sufficient nutrients for plant growth without excess nutrient loss. We concluded, when incorporating as much as 33% compost by volume into a landscape bed, the optimal compost will generally have a C:N ratio of 10-20, P-content <1.0% and a soluble salt content between 1.0 and 3.5 mmhos/cm. These recommendations should ensure optimal plant and soil health and minimize nutrient leaching.

Introduction: The aim is to investigate the possibility of altering the delusional perceptions of psychotic patients by exposing them to a cognitively flexible virtual environment. A flexible vir-tual reality (VR) environment could challenge and enhance the ability to adapt to changing situa-tions and generate novel solutions to core psychotic symptoms. Materials and methods: A systematic review was conducted using different combinations of keywords in different databases. This study was conducted using the PRISMA statement. Results: There is a growing literature on the use of VR to manipulate and normalise perceptual distortions in psychosis. Over the last decade, the number of published studies on VR in mental health has increased 14-fold. Conclusions: A cognitive flexibility virtual environment can alter delusional perception by ex-posing the person to different scenarios that require them to question their assumptions, test their hypotheses, and revise their beliefs. Commonly used biosensors measure heart rate, skin con-ductance and body temperature in relation to different emotional states. Recently, there has been a major shift towards the use of neuroimaging techniques to better understand the pathophysiology of mental disorders. This is where the new wave of biosensor-integrated virtual reality (VR) sys-tems comes in.

This review provides a snapshot of chronic bacterial infections through the lens of Burkholderia pseudomallei; detailing its ability to establish multi-nucleated giant cells (MNGC) within the host, leading to the formation of pyogranulomatous lesions. We explore the role of MNGC in melioidosis disease progression and pathology by comparing the similarities and differences of melioidosis to tuberculosis, outlining the concerted events in pathogenesis that lead to MNGC formation, discussing the factors that influence MNGC formation and how they fit into clinical findings reported in chronic cases. Finally, we speculate about future models and techniques that can be used to delineate the mechanisms of MNGC formation and function.

Lung cancer is the most common malignancy across the world. The new era in lung cancer treatments, especially this past decade, has yielded novel categories of targeted therapy for specific mutations and adjuvant therapy, both of which have led to improved survival rates. In the present study, we review the changes and development of treatments, with a special focus on adjuvant therapy using tyrosine kinase inhibitors (TKIs) administered to non-small-cell lung carcinoma patients who had a complete resection of the tumor harboring a mutated epidermal growth factor receptor. The clinical trials are dating from the past (chemotherapy trials), present (TKIs) and future (ongoing trials).

Bioactive lipids are involved in cellular signalling events with links to human disease. Many of these are involved in inflammation under normal and pathological conditions. Despite being attractive molecules from a pharmacological point of view, detection and quantification of lipids has been a major challenge. Here, we have optimised a liquid chromatography dynamic multiple reaction monitoring targeted mass spectrometry (LC-dMRM-MS) approach to profile eicosanoids and fatty acids in biological samples. In particular, by applying this analytic workflow to study a cellular model of Chronic Myeloid Leukaemia (CML), we found that intra- and extra-cellular 2-Arachidonoylglycerol (2-AG), intracellular Arachidonic Acid (AA), and extracellular Prostaglandin F_2α (PGF_2α), 5-Hydroxyeicosatetraenoic acid (5-HETE), Palmitic acid (PA, C16:0) and Stearic acid (SA, C18:0) were altered in response to immunomodulation by type I Interferon (IFN-I), a currently approved treatment for CML. Our observations indicate changes in eicosanoid and fatty acid metabolism with potential relevance in the context of cancer inflammation and CML.

The popularity of multiparticulate formulations (MPs) as a paediatric dosage form continues to increase. MPs comprise of multiple small units that are easy-to-swallow. Currently, MPs are commonly manufactured into unit doses that are either swallowed whole or opened prior to administration. While this is an acceptable approach, dosing is envisioned to be optimized with a ‘standard’ paediatric device which can better harness the flexible dosing potential of MPs. We evaluated a novel oral syringe (SympfinyTM) that is being developed as a tool to dispense and administer MPs to children. Forty children, 4-12 years old, received 0.5, 1.2, and 2.0 mL doses of placebo MPs using the oral syringe with spring water or a drink of choice to complete sample intake. Acceptability was recorded as those able to completely swallow the dose and participants also rated dose acceptability on a 5-point scale. The ability to completely swallow the dose decreased as dose volume increased; the smallest dose was completely swallowed by 87.5% (35/40) children, and 69.4% (27/39) of children confirmed their willingness to take the sample as a daily medicine. Larger doses, 1.2 and 2.0 mL, gave values of 55% and 57.5% for the doses completely swallowed and 58.8% and 51.72% for willingness to take the sample as a daily medicine, respectively. Use of a drink of choice showed no increase in swallowability as compared with water. The novel oral syringe being developed is an appropriate device for dispensing doses flexibly and administering neutral tasting MPs directly to the mouth in the lower dose range without the need for a co-administration vehicle in children aged 4-12 years.

Retiring coal power plants can reduce air pollution and health damages. However, the spatial distribution of those impacts remains unclear due to complex power system adjustments and pollution chemistry and transport. Focusing on coal retirements in Pennsylvania (PA), we analyze six counterfactual scenarios for 2019 that differ in retirement targets (e.g., reducing 50% of coal-based installed capacity vs. generation) and priorities (e.g., closing plants with higher cost, closer to Environmental Justice Areas, or with higher CO₂ emissions). Using a power system model of the PJM Interconnection, we find that coal retirements in PA shift power generation across PA and the Rest of PJM region leading to scenario-varying changes in the plant-level release of several air pollutants. Due to air pollution chemistry and transport and socio-demographics, these changes in turn give rise to a reduction of 10 to 182 PM_2.5-attributable deaths in PJM across the six scenarios, with most reductions occurring in PA. Scenarios that reduce more coal power generation yield greater aggregate health benefits due to air quality improvements in PA and adjacent downwind regions. In addition, vulnerable populations—in both PA and Rest of PJM—benefit most in scenarios that prioritize plant closures in PA near Environmental Justice Areas. These results demonstrate the importance of considering cross-regional linkages and socio-demographics in designing equitable retirement strategies.

A synoptic review of plant disease epidemics and outbreaks was made using two complementary approaches. The first approach involved reviewing scientific literature published in 2021, in which quantitative data related to new plant disease epidemics or outbreaks were obtained via surveys or similar methodologies. The second approach involved retrieving new records added in 2021 to the CABI Distribution Database, which contains over a million global geographic records of organisms from over 50,000 species. The literature review retrieved 186 articles, describing studies in 62 categories (pathogen species/species complexes) across >40 host species on 6 continents. Pathogen species with >5 articles were: Bursaphelenchus xylophilus, Candidatus Liberibacter asiaticus, cassava mosaic viruses, citrus tristeza virus, Erwinia amylovora, Fusarium spp. complexes, Fusarium oxysporum f. sp. cubense, Magnaporthe oryzae, maize lethal necrosis co-infecting viruses, Meloidogyne spp. complexes, Pseudomonas syringae pvs, Puccinia striiformis f. sp. tritici, Xylella fastidiosa, and Zymoseptoria tritici. Automated searches of the CABI Distribution Database identified 617 distribution records new in 2021 of 283 plant pathogens. A further manual review of these records confirmed 15 pathogens reported in new locations: apple hammerhead viroid, apple rubbery wood viruses, Aphelenchoides besseyi, Biscogniauxia mediterranea, Ca. Liberibacter asiaticus, citrus tristeza virus, Colletotrichum siamense, cucurbit chlorotic yellows virus, Erwinia rhapontici, Erysiphe corylacearum, Fusarium oxysporum f. sp. cubense Tropical Race 4, Globodera rostochiensis, Nothophoma quercina, potato spindle tuber viroid, and tomato brown rugose fruit virus. Of these, 4 pathogens had at least 25% of all records reported in 2021. We assessed two of these pathogens – tomato brown rugose fruit virus and cucurbit chlorotic yellows virus – to be actively emerging in/spreading to new locations. Although three important pathogens – Ca. Liberibacter asiaticus, citrus tristeza virus and Fusarium oxysporum f. sp. cubense – were represented in the results of both our literature review and our interrogation of the CABI Distribution Database, in general our dual approaches revealed distinct sets of plant disease outbreaks and new records, with little overlap.

Phylogenomics has enriched our understanding that the Tree of Life can have network-like or reticulate structures among some taxa and genes. Non-vertical modes of evolution—such as hybridization/introgression and horizontal gene transfer—deviate from a strictly bifurcating tree model, causing non-treelike patterns. Here, we present a brief overview of a phylogenomic workflow for inferring organismal histories and compare methods for detecting reticulate evolution. We discuss how the timing of coalescent events can help disentangle introgression from incomplete lineage sorting and how horizontal gene transfer events can help determine the relative timing of speciation events. In doing so, we identify pitfalls of certain methods and discuss how to extend their utility across the Tree of Life. Workflows, methods, and future directions discussed herein underscore the need to embrace reticulate evolutionary patterns for understanding the timing and rates of evolutionary events, providing a clearer understanding of life’s history.

Machine learning has become an increasingly ubiquitous technology, as big data continues to inform and influence everyday life and decision-making. Currently in healthcare, as well as in most other industries, the two most prevalent machine learning paradigms are supervised learning and transfer learning. Both practices rely on large-scale, manually annotated datasets to train increasingly complex models. However, the requirement of data to be manually labeled leaves an excess of unused, unlabeled data available in both public and private data repositories. Self-supervised learning (SSL) is a growing area of machine learning that has the ability to take advantage of unlabeled data. Contrary to other machine learning paradigms, SSL algorithms create artificial supervisory signals from unlabeled data and pretrain algorithms on these signals. The aim of this review is two-fold: firstly, we provide a formal definition of SSL, divide SSL algorithms into their four unique subsets, and review the state-of-the-art published in each of those subsets between the years of 2014-2020. Second, this work surveys recent SSL algorithms published in healthcare, in order to provide medical experts with a clearer picture of how they can integrate SSL into their research, with the objective of leveraging unlabeled data.

Understanding of the molecular mechanisms of prostate cancer has led to development of therapeutic strategies targeting androgen receptor (AR). These androgen-receptor signaling inhibitors (ARSI) include androgen synthesis inhibitor- abiraterone and androgen receptor antagonists- enzalutamide, apalutamide, and darolutamide. Although these medications provide significant improvement in survival among men with prostate cancer, drug resistance develops in nearly all patients with time. This could be through androgen-dependent or androgen-independent mechanisms. Even weaker signals and non-canonical steroid ligands can activate AR in the presence of truncated AR-splice variants, AR overexpression, or activating mutations in AR. AR splice variant, AR-V7 is the most studied among these and is not targeted by available ARSIs. Non-androgen receptor dependent resistance mechanisms are mediated by activation of an alternative signaling pathway when AR is inhibited. DNA repair pathway, PI3K/AKT/mTOR pathway, BRAF-MAPK and Wnt signaling pathway and activation by glucocorticoid receptors can restore downstream signaling in prostate cancer by alternative proteins. Multiple clinical trials are underway exploring therapeutic strategies to overcome these resistance mechanisms.

Chikungunya virus (CHIKV) is an alphavirus that causes febrile illness punctuated by severe polyarthralgia. After the emergence of CHIKV in the Western Hemisphere, multiple reports of congenital infections were published that documented neurological complications, cardiac defects, respiratory distress, and miscarriage. The Western Hemisphere is endemic to several alphaviruses and whether antigenic cross-reactivity can impact the course of infection has not been explored. Recent advances in biomedical engineering have produced cell co-culture models that replicate the cellular interface at the maternal fetal axis. We employed a trans-well assay to determine if cross-reactive antibodies affected the movement and replication of CHIKV across placental cells and into an embryoid body. The data show that antibodies to Venezuelan equine encephalitis virus (VEEV) significantly reduced CHIKV viral load in embryoid bodies. The data highlight that viral pathogenesis can be cell-specific and that exploiting antigenic cross-reactivity could be an avenue for reducing the impact of congenital CHIKV infections.

Antimicrobial peptides and structurally related peptoids offer potential for the development of new antibiotics. However, progress has been hindered by challenges presented by poor in vivo stability (peptides) or lack of selectivity (peptoids). Herein, we have developed a process to prepare novel hybrid antibacterial agents that combine both linear peptoids (increased in vivo stability compared to peptides) and a nisin fragment (lipid II targeting domain). The hybrid nisin-peptoids prepared were shown to have low µM activity (comparable to natural nisin) against methicillin-resistant Staphylococcus aureus.

Coronaviruses are a large family of diverse enveloped RNA viruses found in numerous animal species. They are well-known for their ability to cross species barriers and have been transmitted from bats or intermediate hosts to humans on several occasions. Four of the seven human coronaviruses (hCoVs) are responsible for approximately 20% of common colds (hCoV-229E, -NL63, -OC43, -HKU1). Two others (SARS-CoV-1 and MERS-CoV) cause severe and frequently lethal respiratory syndromes but have only spread to very limited extents in human populations. In contrast, SARS-CoV-2, while exhibiting intermediate pathogenicity, has a profound impact on public health due to its enormous spread. In this review, we discuss which initial features of the SARS-CoV-2 Spike protein and subsequent adaptations to the new human host may have helped this pathogen to cause the COVID-19 pandemic. Our focus is on host forces driving changes in the Spike protein and their consequences for virus infectivity, pathogenicity, immune evasion and resistance to preventive or therapeutic agents. In addition, we discuss the significance and perspectives of broad-spectrum therapeutics and vaccines.

High level of noise is a disturbance to the human environment. Noise in industries is also an occupational hazard because of its attendant effects on workers’ health. Noise presents health and social problems in industrial operations, and the source is related to the machineries used in the industries. One of the unique features of the noise associated with wood machinery is the level of exposure and duration. Equipment used in a factory can be extremely loud. They can produce noise at decibels high enough to cause environmental health and safety concerns. The mechanically driven transport and handling equipment, cutting, milling, shaping and dust extractor installations in the wood industry generate noise. The sources of noise pollution have increased due to non-compliance with basic safety practices. The increased use of locally fabricated machine in the industry has increased the level of noise and vibration. The effects of industrial noise pollution as discussed include: increase in blood pressure; increased stress; fatigue; vertigo; headaches; sleep disturbance; annoyance; speech problems; dysgraphia, which means reading/learning impairment; aggression; anxiety and withdrawal. As presented in this paper, noise control techniques include; sound insulation, sound absorption, vibration damping and Vibration isolation.

Pharmaceutical poisoning is a significant global public health concern, causing approximately 190,000 deaths yearly. This scoping review aims to comprehensively map the available literature on pharmaceutical poisoning and compare patterns between high-income countries (HICs) and low-middle-income countries (LMICs). A systematic search was performed across the following databases: Embase, PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and CINAHL. Studies included were from 1st January 2011 to 31st December 2020, in English, with full text available. Seventy-nine articles were included in the study; 21 were from LMICs and 58 were from HICs. The toxic exposure was largely intentional (77%) in LMICs and accidental (68%) in HICs. Drugs acting on the nervous system were responsible for 95% of toxicities worldwide with analgesics accounting for the largest subtherapeutic group in both LMICs (40%) and HICs (58%). Notable statistics were that HICs accounted for 99% of opioid overdoses, and LMICs accounted for 19% of anti-epileptic-induced toxicities. Overall, the medical outcomes of poisonings were generally worse in LMICs. The review provides possible interventions to target specific geographic locations, based on the trends identified, to reduce the burden worldwide. Many gaps within the literature were recognised, calling for more robust analytical research.

Actively combating post-harvest food spoilage and waste can dramatically increase the efficiency of food utilization worldwide. In climacteric fruits, chemical treatments such as 1-MCP are an effective way of reducing post-harvest spoilage and waste by inhibiting the fruit’s ability to perceive ethylene. 1-MCP treatment is increasingly being used to explore the complex nature of ripening physiology at a fundamental level, however, differences in application and quantitation methods create difficulties in comparing conclusions across studies. Here we report an effective and reproducible method for 1-MCP application and quantitation for small-medium sized research applications. By use of surrogate alkene standards 1-butene and cis-2-butene, the highly volatile and elusive 1-MCP molecule can be identified and quantified by gas chromatography and subsequent standard curves may be developed. It is hoped that the methodology outlined here can help standardize consistent 1-MCP application for post-harvest research without excessive investment in specialized equipment.

Contemporary advanced models for aspect-targeted opinion word extraction (ATOWE), which predominantly utilize BERT-based encoders at a word level, have shown limited advancements when integrated with graph convolutional networks (GCNs) for syntactic tree assimilation. Recognizing the prowess of BERT subwords in encapsulating rare or context-poor words, this study pivots from syntactic trees to BERT subwords, omitting GCNs from the structural framework. Our approach, named Aspect-Enhanced Wordpiece Extraction Model (AEWEM), focuses on refining aspect representation during encoding. We propose an input format of paired sentence-aspect, diverging from traditional single-sentence inputs. AEWEM demonstrates superior performance on benchmark datasets, establishing a robust foundation for future explorations in this domain.

Malnutrition and dental caries in early childhood remain persistent and intertwined global health challenges, particularly for indigenous and geographically-remote populations. To examine the prevalence and associations between early childhood dental caries, parent-reported mouth pain and malnutrition in the Amazonian region of Ecuador, we conducted a cross-sectional study of the oral health and nutrition status of 1,407 children from birth through age 6 in the “Alli Kiru” program (2011-2013). We used multivariate regression analysis to examine relationships between severe caries, parent-reported mouth pain measures, and nutritional status. The prevalence of dental caries was 65.4%, with 44.7% of children having deep or severe caries, and 33.8% reporting mouth pain. The number of decayed, missing and filled teeth dmft) increased dramatically with age. Malnutrition was prevalent, with 35.9% of children stunted, 1.1% wasted, 7.4% underweight, and 6.8% overweight. As mouth pain increased in frequency, odds for severe caries increased. For each unit increase in mouth pain frequency interfering with sleeping, children had increased odds for underweight (AOR: 1.27; 95% CI: 1.02 – 1.54) and decreased odds for overweight (AOR: 0.76; 95% CI: 0.58 – 0.97). This relationship was most pronounced among 3-6 year-olds. Early childhood caries, mouth pain and malnutrition were prevalent in this sample of young children. Parent-reported mouth pain was associated with severe caries, and mouth pain interfering with sleeping was predictive of poor nutritional status. We demonstrate the utility of a parsimonious parent-reported measure of mouth pain to predict young children’s risk for severe early childhood caries and malnutrition, which has implications for community health interventions.

Precision medicine seeks to use genomic data to help provide the right treatment to the right patient at the right time. Next-generation sequencing technology allows for the rapid and accurate sequencing of many genes at once. This technology is becoming more common in oncology, though the clinical benefit of incorporating it into precision medicine strategies remains under significant debate. In this manuscript, we discuss the early findings of the impact of next-generation sequencing on cancer patient outcomes. We investigate why not all patients with genomic variants linked to a specific therapy receive that therapy and describe current barriers. Finally, we explore the current state of health insurance coverage for individual genome sequencing and targeted therapies for cancer. Based on our analysis, we recommend increased transparency around the determination of “actionable mutations” and a heightened focus on investigating the variations in health insurance coverage across patients receiving sequencing-matched therapies.

As the global overprovisioning of electronic devices continues to rise, the management of electronic waste (e-waste) has developed as a significant challenge. E-waste is comprised of hazardous materials; moreover, the toxic constituents in them can impact the environment and public health through improper disposal. On the beneficial side, this e-waste also contains some valuable materials. If the valuable materials are recovered, they can reduce the dependence on new, raw materials. Conventional linear models of production and consumption have led to a momentous buildup of e-waste, posing environmental and economic risks. This paper examines how the adoption of a circular economy approach can improve e-waste recycling in Nairobi by evaluating its economic recovery potential and e-waste residuals. It introduces metrics to assess the development of circular economy practices to help in the handling of e-waste residuals and examines the economic consequences associated with the adoption of circular strategies.

We study spherically symmetric spacetimes in Einstein-aether theory in three different coordinate systems, the isotropic, Painlev\`e-Gullstrand, and Schwarzschild coordinates, and present both time-dependent and time-independent exact vacuum solutions. In particular, in the isotropic coordinates we find a class of exact static solutions characterized bya single parameter $c_{14}$ in closed forms, which satisfies all the current observational constraints of the theory, and reduces to the Schwarzschild vacuum black hole solution in the decoupling limit ($c_{14} = 0$). However, as long as $c_{14} \not= 0$, a marginally trapped throat with a finite non-zero radius always exists, and in one side of it the spacetime is asymptotically flat, while in the other side the spacetime becomes singular within a finite proper distance from the throat, although the geometric area is infinitely large at the singularity. Moreover, the singularity is a strong and spacetime curvature singularity, at which both of the Ricci and Kretschmann scalars become infinitely large.

Public participation is significant for the success of any urban planning project. However, most members of the general public are not planning professionals and may not understand the technical details of a 2D paper-based plan, which might hamper their participation. One way to expand the participation of citizens is to present plans in well-designed, user-friendly and interactive platforms that allow participation regardless of the technical skills of the participants. This paper investigates the impacts of the combined use of 3D visualization and E-participation on public participation in Kisumu, Kenya. A 3D City model, created with CityEngine2016, was exported into a web-based geo-portal and used as a Planning Support System in two stakeholder workshops in order to evaluate its usability. For e-participation, 300 questionnaires given out to planning practitioners. Five indicators were developed for evaluating the usability of the 3D model while the usability of e-participation was evaluated using communication, collaboration and learning as indicators. Results showed that effectiveness and efficiency varies within different professional groups while the questionnaires showed strong preference for e-participation methods, especially SMSs/USSDs and emails. The study concludes that the use of 3D visualization and E-participation has the potential for improving the quality and quantity of public participation and recommends further research on the subject.

Box tree moth, Cydalima perspectalis is native to East Asia where it occurs on Buxus trees. Its natu-ral distribution includes China, Japan, Korea and India, and it was accidentally introduced into Europe, Middle East, North America and north Africa through the trade in Buxus spp., where it can cause considerable damage. In the native range of C. perspectalis, three tachinids (Diptera, Tachinidae) are known to parasitize larvae of C. perspectalis, including Exorista sp., Pseudoperichaeta nigrolineata (Walker 1853) and Compsilura concinnata (Meigen 1824). Data on tachinid parasitoids parasitizing C. perspectalis on the European continent include only P. nigrolineata. Field collection of mature larvae and pupae of C. perspectalis during July 2020 in four locations in Split – Dalmatia County in Croatia resulted in collection of live tachinid larvae that were reared to adults. The tachinid specimens were identified at the Natural History Museum, London, UK, as Nemorilla flo-ralis (Fallén, 1810) (Diptera, Tachinidae). Conservatively, 1.2 – 2.4 % parasitism rate was achieved. This is the first world record of N. floralis parasitism on C. perspectalis larvae, which can be added as a potential tool for C. perspectalis biological control.

Mount Hamiding Protected Forest is located in North Halmahera Regency, North Maluku Province, the Wallace zone has an important role in providing protection functions, life support systems and regulating water management, preventing floods, preventing seawater intrusion, and controlling soil fertility. The protected forest area in the Wallace Zone is globally renowned for its endemic characteristics of flora and fauna. The condition of the protected forest of Mount Hamiding HMPF is currently experiencing anthropogenic damage as a result of forest encroachment, illegal logging, shifting cultivation, grazing and poaching to meet social needs. Anthropogenic damage has been in the spotlight for decades and has become a global issue. This study aims to determine damage to protected forests, changes in land cover, and mitigation of protected forest areas. This research uses quantitative and descriptive qualitative methods. Determination of research locations by purposive sampling. Parameters measured in this study were damage to protected forests, changes in land cover and area mitigation strategies. To identify forest damage, snowball sampling was carried out, and land cover changes through land cover data processing were obtained from the Ministry of Environment and Forestry of the Republic of Indonesia. Then using Imagery 7 ETM+ and 8 OLI to calculate changes in forested land to non-forested from 2006 -2021, analysis of land cover change using supervised classification, developing a strategy based on identity verification of forest damage and analysis of land cover change. The results showed that damage to protected forests was caused by anthropogenic disturbances in the form of forest encroachment, shifting cultivation, illegal logging, grazing and hunting of wild animals. Changes in land cover experienced the greatest damage in 2006-2021 amounting to 1,796.54 ha (16.17%). Strategic efforts are carried out using forest engineering, namely the agroforestry system and social engineering through community empowerment, namely training and outreach.

In the current study, we assessed the effects of conventional and Ultra High Dose Rate (UHDR) irradiation on behavioral and cognitive performance one month following exposure and assessed whether these effects were associated with alterations in the number of immune cells in the hippocampus using flow cytometry. Conventional- and UHDR-irradiated mice showed impaired novel object recognition. During fear learning, conventional- and UHDR-irradiated mice moved less during the inter-stimulus-interval (ISI) and UHDR-irradiated mice also moved less during the baseline period (prior to the first tone). In irradiated mice, reduced activity levels were also seen in the home cage; conventional- and UHDR-irradiated mice moved less during the light period and UHDR-irradiated mice moved less during the dark period. Following behavioral and cognitive testing, infiltrating immune cells in the hippocampus were analyzed by flow cytometry. The percent Ly6G+ CD45+ cells in the hippocampus was lower in conventional- and UHDR-irradiated than sham-irradiated mice, suggesting that neutrophils might be particularly sensitive to radiation. The percent of Ly6G+ CD45+ cells in the hippocampus was positively correlated with the time spent exploring the novel object in the object recognition test, suggesting that the reduced percent Ly6G+ CD45+ cells in the hippocampus might mediate some of the detrimental radiation-induced cognitive effects.

While referral-level medicine is important in the veterinary curriculum, students also need a solid base knowledge of clinically relevant routine surgery and diagnostic skills. Veterinary hospitals must maintain a steady caseload that provides wellness cases and commonly encountered conditions. Shelter Medicine programs can create the opportunities to meet these challenges. Students can gain quantifiable surgical experience in spay/neuter with measured growth in surgical efficiency and competency while providing needed community service for animal shelters. Students can directly interact with shelter animals by performing examinations, diagnostic testing, and development of treatment protocols and recommendations for commonly encountered problems. Furthermore, students can obtain a working knowledge of biosecurity on a population level to minimize risk of infectious diseases spreading to healthy populations.

To improve accessibility, this article describes a static, four-legged, walker that can be constructed from materials and fasteners commonly available from hardware stores coupled by open-source 3-D printed joints. The designs are described in detail, shared under an open-source license, and fabricated with a low-cost open-source desktop 3-D printer and hand tools. The resulting device is loaded to failure to determine the maximum load that the design can safely support in both vertical and horizontal failure modes. The experimental results showed the average vertical failure load capacity was 3680±694.3N, equivalent to 375.3±70.8kg of applied weight with the fractured location at the wood dowel handlebars. The average horizontal load capacity was 315.6±49.4N, equivalent to 32.2±5.1kg. The maximum weight capacity of a user of 187.1±29.3kg was obtained, which indicates the open-source walker design can withstand the weight requirements of all genders with a 95% confidence interval that includes a safety factor of 1.8 when considering the lowest deviation weight capacity. The design has a cost at the bottom of the range of commercial walkers and reduces the mass compared to a commercial walker by 0.5kg (19% reduction). It can be concluded that this open-source walker design can aid accessibility in low-resource settings.

Increasingly measured data in the context of smart cities can be used to develop new and innovative business models to increase efficiency and the value of life. A time-series classification algorithm can support to automatize many different processes such as forecasting services. In order to ensure data security and privacy, Federated Learning trains a global model collaboratively on multiple clients. Having different data-distributions and data-quantities across participating clients, neural networks suffer from slow convergence and overfitting. Based on different data-distributions, data-quantities and number of clients, we develop and evaluate different data-clustering strategies to update global model weights in comparison to the state of the art. We use public time-series data, generate various synthetic datasets and train a Relational-Regularized Autoencoder for classification purposes. Our results show an improvement of model performance concerning generalization.

A new picture of the Josephson effect is devised. The radio-frequency (RF) signal, observed in a Josephson junction, is shown to stem from bound electrons, tunneling periodically through the insulating film. This holds also for the microwave mediated tunneling. The Josephson effect is found to be conditioned by the same prerequisite worked out previously for persistent currents, thermal equilibrium and occurence of superconductivity. The observed negative resistance behaviour is shown to originate from the interplay between the normal and superconducting currents.

Verteporfin, a free base benzoporphyrin derivative monoacid ring A, is a photosensitizing drug for photodynamic therapy (PDT) used in the treatment of the wet form of macular degeneration and activated by red light of 689 nm. Here, we present the first direct study of its photofragmentation channels in the gas-phase, conducted using a laser interfaced mass spectrometer across a broad photoexcitation range from 250-790 nm. The photofragmentation channels are compared with the collision-induced dissociation (CID) products revealing similar dissociation pathways characterized by the loss of the carboxyl and ester groups. Complementary solution-phase photolysis experiments indicate that photobleaching occurs in verteporfin in acetonitrile; a notable conclusion, as photoinduced activity in Verteporfin was not thought to occur in homogenous solvent conditions. These results provide unique new information on the thermal break-down products and photoproducts of this light-triggered drug.

Functional mobility assessments (i.e., Timed Up and Go) are commonly used clinical tools for mobility and fall risk screening in the aging population. In this work, we proposed a new Mixed Reality (MR)-based assessment that utilized a Microsoft HoloLens^TM headset to automatically lead and track the performance of functional mobility tests, and subsequently evaluated its validity in comparison with reference inertial sensors. Twenty-two healthy adults (10 older, 12 young) participated in this study. An automated functional mobility assessment app was developed based on the HoloLens platform. Mobility performance was recorded with the headset built-in sensor and validated with reference inertial sensor (Opal, APDM) taped on the headset and lower back. Results indicate vertical kinematic measures by HoloLens was in good agreement with the reference sensor (Normalized RMSE ~ 10%). Additionally, the HoloLens-based test completion time was in perfect agreement with clinical standard stopwatch measure. Overall, our preliminary investigation indicates that it is possible to use an MR headset to automatically guide users to complete common mobility tests with good measurement accuracy, thus it has great potential to provide objective and efficient sensor-based mobility assessment.

A classical model is presented for persistent currents in superconductors. Their existence is argued to be warranted because their decay would violate the second law of thermodynamics. This conclusion is achieved by analyzing comparatively Ohm's law and the Joule effect in normal metals and superconducting materials. Whereas Ohm's law applies in identical terms in both cases, the Joule effect is shown to cause the temperature of a superconducting sample to \textit{decrease}. An experiment is proposed to check the validity of this work in superconductors of both types I and II.

Under the extreme shortage of water resources in the Yellow River Basin, it is of great signifi-cance to analyze the spatial distribution relationship between rural settlement and water re-sources for the coordinated development of human and water resources in the Yellow River Ba-sin. However, the water allocation scheme depended on statistical data in the previous work, not on rural settlements in space. Furthermore, previous researches seldom focus on the evaluation of surface water resources accessibility according to the spatial distribution characteristics of ru-ral settlements and water resources, especially, in the Yellow River Basin and using rural set-tlement as unit. Therefore, a quantitative evaluation model of surface water resources accessibil-ity is constructed by using the GIS network analysis method, taking rural settlement as the re-search unit, based on three dimensions of topography, distance, and surface water resources, at the Yellow River basin scale. The results show that: (1) The surface runoff of rural settlement in the Yellow River basin is mostly less than 0.05 km/m2, reaching 99.83%. In other words, the Yel-low River Basin is extremely short of water resources. The surface water resources accessibility is affected by distance, topography, and surface water resources. The evaluation results show that the range of surface water resources accessibility is 0.13~0.88, with an average value of 0.47 and a standard deviation of 0.05. The High surface water resources accessibility value in the Yel-low River Basin is in the east and west, and the low value is mainly distributed in the middle. (2) The range from low to high of surface water resources accessibility in 12 catchments is Sanmen-xia station, Lanzhou station, Shizuishan station, Longmen station, Tongguan station, Toudaoguai station, Xiaolangdi station, Huayuankou station, Lijin station, Gaocun station, Ai Shan station and Tangnaihai station. (3) The value of surface water resources accessibility at the city scale is higher in the east of 10 cities and in the west of 1 city. However, it is lower in the west of 9 cities. And the values of the other cities are at a medium level. The correlation coefficient with primary industry GDP and surface water resources accessibility is 0.271 (N=56, Sig=0.043, in 0.05 level, the correlation is significant), which verifies the rationality of surface water resources accessibility model to some extent.

The maker movement has reached the optics labs, empowering researchers to actively create and modify microscope designs and imaging accessories. 3D printing has especially had a disruptive impact on the field, as it entails an accessible new approach in fabrication technologies, namely additive manufacturing, making prototyping in the lab available at low cost. Examples of this trend are taking advantage of the easy availability of 3D printing technology. For example, inexpensive microscopes for education have been designed, such as the FlyPi. Also, the highly complex robotic microscope OpenFlexure represents a clear desire for the democratisation of this technology. 3D printing facilitates new and powerful approaches to science and promotes collaboration between researchers, as 3D designs are easily shared. This holds the unique possibility to extend the open-access concept from knowledge to technology, allowing researchers from everywhere to use and extend model structures. Here we present a review of additive manufacturing applications in microscopy, guiding the user through this new and exciting technology and providing a starting point to anyone willing to employ this versatile and powerful new tool.

Preterm infants often experience frequent intermittent hypoxia (IH) episodes which is associated with neuroinflammation. We tested the hypotheses that early caffeine and/or non-steroidal in-flammatory drugs (NSAIDs) confer superior therapeutic benefits for protection against IH-induced neuroinflammation than late treatment. Newborn rats were exposed to IH or hy-peroxia (50% O2) from birth (P0) to P14. For early treatment, the pups were administered: 1) dai-ly caffeine citrate (Cafcit, 20 mg/kg IP loading on P0, followed by 5 mg/kg from P1-P14); 2) ke-torolac topical ocular solution in both eyes from P0 to P14; 3) ibuprofen (Neoprofen, 10 mg/kg loading dose on P0 followed by 5 mg/kg/day on P1 and P2); 4) caffeine+ketorolac co-treatment; 5) caffeine+ibuprofen co-treatment; or 6) equivalent volume saline. On P14, animals were placed in room air (RA) with no further treatment. For late treatment, pups received similar treatments from P15-P21 (caffeine and/or ketorolac), or P15-P17 (ibuprofen). RA control were similarly treated. At P21, whole brains were assessed for histopathology, apoptosis, mye-lination, and biomarkers of inflammation. IH caused significant inflammation, reduced mye-lination, and apoptosis in preterm rat brains, an effect that was improved predominantly with combined caffeine/NSAID early treatment. Early caffeine/NSAID co-treatment confers syner-gistic neuroprotection against IH-induced damage.

The Mediterranean diet (MedDiet) is recognised to reduce risk of coronary heart disease (CHD), in part, via its anti-inflammatory properties. Diet efficacy via this mechanism is however unclear in patients with diagnosed CHD. This study aimed to determine the effect of MedDiet versus low-fat diet intervention on inflammatory biomarkers and adiposity in a pilot cohort of Australian patients post coronary event. Participants (62±9 years, 83% male) were randomised to the MedDiet (n=34) or low-fat diet (n=31). At 0-, 3- and 6-months, dietary counselling, anthropometry, body composition (Dual-energy X-ray Absorptiometry) and venepuncture was conducted. Participants adhered well to the MedDiet intervention, however, there were no significant changes in body composition or inflammatory biomarkers hs-C-reactive protein or hs-interleukin-6 in the MedDiet compared to the low-fat diet group after 6-months. Adiponectin, an anti-inflammatory adipokine, tended to increase in response to the MedDiet (+1.1±4.2ng/mL, p=0.11) and decrease in response to the low-fat diet (-0.9±3.3ng/mL, p=0.20). In the pooled cohort, participants with greatest improvement in MedDiet adherence score had significantly lower waist circumference and subcutaneous fat levels at 6-months. A clinically significant effect of the MedDiet on inflammation and adiposity in CHD patients may require a larger sample, adjunct exercise intervention and/or caloric restriction.

Future healthcare professionals can play a significant role in managing those with thoughts of suicide. This scoping review aims to determine healthcare students’ knowledge and attitude towards suicide. A systematic search was conducted across five databases: PubMed, CINAHL, EMBASE, PsycINFO, Cochrane, and DARE. Only primary studies written in English, from database inception until 31st December 2023 were included. A total of 44 studies were included. Overall, healthcare students demonstrated low to moderate confidence in managing patients with thoughts of suicide and low levels of relevant education despite acknowledging their importance in preventing suicide. Increased personal exposure to suicide was associated with increased suicide literacy, confidence in managing patients with thoughts of suicide, and reduced stigma. Demographics and culture were shown to affect knowledge and attitude as well. Further research is needed to better understand various contributing factors to healthcare students’ knowledge and attitude regarding suicide. Evaluating healthcare curricula should be considered to implement effective suicide training program.

The rapid growth of the elderly population is a major global demographic and social issue. Unfortunately, there is a shortage of pension plans and social se-curity programmes for this population in developing countries which has severe consequences for their quality of life and planetary health (PH) wellbeing. In this article, we aimed to better understand the pension systems in Ghana, Pakistan, and Myanmar, by reviewing the official government materials (such as pension reports) and published literature. We observed several policy implementation gaps and inequity in pension schemes for older people, specifically for informal and private sector workers. Considering the size of formal versus informal economies and the level of development index of each country, we suggest a wide variety of options in pension policies, financing, designing cash benefits and pension payments to cover all older citizens. This article addresses an unmet need of the elderly people, their wider environmental and economic sustainability to ensure social justice and resource utilization. The governments of developing countries should embrace and establish unique, inclusive, and friendly policies encompassing the informal sector to warrant older adults’ functional and planetary wellbeing with dignity and honor.

Small ruminant lentivirus (SRLV) are infected and transmitted among ovine and caprine species. This disease is a severe problem for small ruminant production, not only for animals’ wellbeing but also for the herd’s efficiency. The main aim of this research was to quantify the seroprevalence and associated risk factors for SRLV infection in the north region of Portugal. Collected samples from a total of 150 herds, of which 129 (86.0%; 95% CI: 80.67% - 91.33%) had at least one seropositive animal. Out of 2607 individual blood samples, 1074 (41.2%) were positive for SRLV. The risk factors associated with SRLV infection were: specie (caprine), age (&gt; 2 years old), herd size (&gt; 100 animals), production system (intensive), production aptitude (milk), type of activity (professional), participation in livestock competitions (yes), buy replacement young ewe (yes) and rearing (natural). This knowledge empowers the implementation of effective preventive measures. Overall, biosecurity measures should be promoted and implemented to aim reducing viral transmission, with the main goal of reducing the prevalence of this disease. Completely, we understand that government authorities should promote and audit voluntary control and eradication programs in small ruminant herds in the region studied.

Road traffic accidents are associated with different factors, such as non-signalized road networks, inexperienced drivers, lack of communication skills, distraction, and visual or cognitive impairment of road users, which have led to this increase in traffic accidents. Understanding these factors in alignment with road user communication skills can provide solutions that can reduce traffic fatalities. Road users’ communication is predominantly formal in nature, but informal means of communication also exist but are not given proper attention during the driving training and licence testing processes. Therefore, this study investigated communication skills between drivers as a factor contributing to traffic accidents in South African cities. Consequently, 16 traffic scenarios of communication between drivers were simulated using PTV Vissim and Blender software, and a semistructured interview questionnaire was used to collect data from South African road users. The questionnaire was further used to evaluate the confidence level of road users concerning informal communication. The data were analysed via regression analysis to establish the relationship between traffic accidents and miscommunication between drivers. The information gathered and analysed from this study helps to understand the informal communication types between drivers and establish where communication loss exists, which ultimately leads to a traffic accident. The results also show that misinterpretation of communication signals can present the possibility of traffic safety risk.

Background: Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low levels of a constant current via scalp electrodes to specifically targeted areas of the brain. The effects of tDCS on whole-body exercise performance has been of interest in recent literature. The purpose of the current investigation was to investigate if tDCS, administered via Halo Sport, influences time trial performance in trained cyclists, and if changes in exercise performance are associated with prefrontal cortex (PFC) activation and/or muscle oxygenation (SmO2). Methods: Twelve recreationally trained cyclists volunteered to participate in two 10-kilometer time trials following 20 minutes of tDCS or a sham condition. Results: T-tests showed there was no significant difference in performance (time to completion) or physiological measures (BLa-, HR, SmO2, PFC oxygenation) between the Halo and sham conditions. Conclusions: These results indicate that the application of tDCS via Halo Sport does not induce changes in exercise performance or related physiological parameters during a 10-kilometer cycling time trial.

There is a need for strategic healthcare workforce planning to address shortages and ensure universal health coverage, aiming to optimize work-force per population ratio, distribution, and competencies. Amidst rising demands exacerbated by aging populations and events like the COVID-19 pandemic, strategic workforce planning becomes crucial for addressing healthcare inequalities by forecasting needs, bridging skill gaps, and adapting to changing demographics and care models. Israel has invested in strategic planning to tackle healthcare workforce challenges; however, globally there is insufficient planning informed by health labor market analysis, which hinders efforts to address healthcare inequalities. The paper reviews national policies in Israel, Australia, Germany, and Norway, ex-amining statistics and government publications to highlight strategic plan-ning considerations and address challenges in healthcare workforce plan-ning. This paper focuses both on the critical role of physicians in healthcare systems, and on the changing borders between healthcare professions and different national contexts which demand more context dependent strategic workforce planning. We highlight common themes among national policies, including the need for data collection, increasing the capacity of domestic training programs, and the need to address geographic maldistribution of physicians. Ultimately, we aim to guide policy in the development of a re-silient and sustainable healthcare workforce capable of meeting diverse community needs and promoting equity in healthcare services.

Entheseal spinal inflammation and new bone formation with progressive ankylosis may occur in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). This study evaluated whether JAK inhibition with tofacitinib modulated the key disease associated cytokines, TNF and IL-17A and whether tofacitinib also modulated bone marrow stromal cell-derived mesenchymal stem cells (MSCs) function including osteogenesis, since post inflammation new bone formation occurs in these conditions. Methods: Conventional entheseal derived αβ CD4+ and CD8+ T-cells were in-vestigated following anti-CD3/CD28 bead stimulation to determine IL-17A and TNF levels in Tofacitinib treated (1000nM) peri-entheseal bone (PEB) and peripheral blood mononuclear cells (PBMC) following ELISA. Bone marrow stromal cell-derived mesenchymal stem cells (MSCs) colony forming unit (CFU-F) and multilineage potential was evaluated using tofacitinib (dosag-es ranging between 100, 500, 1000 and 10000nM). Results: Induced IL-17A and TNF cytokine production from both entheseal CD4+ T-cells and CD8+ T-cells were effectively inhibited by to-facitinib. Tofacitinib treatment did not impact on CFU-F potential or in vitro chondro- and oste-ogenesis. However, tofacitinib stimulation increased MSC adipogenic potential with greater Oil Red O stained area. Conclusion: Inducible IL-17A and TNF production by healthy human enthe-seal CD4+ and CD8+ T-cells was robustly inhibited in vitro by tofacitinib. However, tofacitinib did not impact on MSC osteogenesis but stimulated in vitro MSC adipogenesis, the rele-vance of which needs further evaluation given the adipocytes are associated with new bone formation in SpA.

Heat-stressed lactating dairy cattle exhibit unique metabolic symptoms; many of which are undoubtedly involved in heat-induced subfertility. Because of its known systemic effects, we hypothesized that γ-aminobutyric acid (GABA) participates in the regulation of insulin and progesterone during heat stress. Multiparous lactating Holstein cows (n=6) were studied during four experimental periods: 1) thermoneutral (TN; d 1-5), 2) TN + hyperinsulinemic-hypoglycemic clamp (d 6-10), 3) heat stress (HS; d 16-20), and 4) HS + euglycemic clamp (d 21-25). Blood samples were collected once daily via coccygeal venipuncture into heparinized evacuated tubes. Analysis of GABA concentrations from all four treatment periods yielded no differences. In direct comparison to TN concentrations, plasma GABA tended to be decreased during HS (16.57±2.64 vs 13.87±2.28 ng/ml, respectively, P = 0.06). Both milk production and plasma insulin were moderately correlated with plasma GABA (r=0.35, P<0.01; r = -0.32, P<0.01). Plasma progesterone was correlated with plasma GABA concentrations during TN but not HS. These results are the first to indicate that peripheral GABA could be involved in regulating aspects of production and reproduction during heat stress. More research is needed to determine its precise role(s).

Causal language can be a powerful tool for media outlets to subtly influence public perception and reinforce specific narratives. Therefore, identifying these linguistic patterns can be helpful in assessing the level of bias present in media content. In this paper, we directly compare the prevalence of causal language in headlines pertaining to the coverage of the Israel-Palestine conflict and the Russia-Ukraine war. We specifically look at the BBC and AlJazeera headlines covering the assault on Gaza since October 7, 2023. We use UniCausal, a model for causal text mining, in order to automatically extract the cause and effect of each headline. Our findings reveal that BBC headlines tend to avoid directly attributing causality to Israel for the violence in Gaza, whereas Al Jazeera headlines explicitly identify Israel as the responsible party. This differential use of causal language suggests a potential bias in media reporting.

The phenomena of light absorption, fluorescence and laser emission are accounted for within a unique picture. The atomic dipole is dealt with in a quantum framework, whereas the electromagnetic field is assumed to be a classical sine-wave. The on and off resonance cases are investigated. This is achieved owing to a novel application of Poynting's theorem. Observable predictions are made, regarding absorption of the electromagnetic energy and the frequency bandwidth of light emitted either by fluorescence or laser effect.

In the mid-1950s, Bert L. Vallee and his colleague Marvin Margoshes discovered a molecule known today as metallothionein (MT). Meanwhile MTs have been shown to be common in many biological organisms. Despite their prevalence, however, it remains unclear to date what exactly MTs do and how they contribute to the biological function of an organism or organ. Honoring Dr. Vallee’s sometimes innovative approach to research, this contribution sets out to show how philosophy of science can help us gain a clearer picture of biochemical research. We shall look into both the discovery of as well as recent research on Dr. Vallee’s beloved family of MT proteins to illustrate (i) how exploratory and upward-looking research play important roles in biochemical discoveries although they do not fit the paradigmatic approach of decomposition and struc-ture-function mapping. Besides, we shall suggest (ii) that while other biochemical molecules ex-hibit a clearly identifiable function, other research hypotheses might be worthy of pursuit in the case of MTs.

Chronic myeloid leukemia (CML) is the most common form of leukemia in adults and accounts for approximately 15% of all leukemia cases. The etiology of this disease is based on the presence of the oncogenic Bcr/Abl fusion protein, which has dysregulated tyrosine kinase activity. This pathological condition is the result of a chromosomal translocation between chromosomes 9 and 22 leading to the formation of the Philadelphia chromosome (Ph). Clinical establishment of targeted therapy with Abl kinase inhibitors (AKIs) has been observed in the treatment of CML. Therapy resistance in patients with CML is due to genetic alterations in the cells of CML, specifically affecting the Bcr/Abl oncoprotein. Acquired resistance of CML patients to tyrosine kinase inhibitors (AKIs) has also been associated with the tumor microenvironment (TME). This study aimed to examine the role of hypoxic conditions in the development of chemoresistance to certain AKIs in CML. The findings of our study indicate that exposure to hypoxic conditions leads to a substantial increase in chemoresistance to crizotinib, while only resulting in a slight increase in chemoresistance to imatinib. It is worth noting that both drugs effectively block Bcr/Abl function. Furthermore, it was observed that the inclusion of the JAK1/2 inhibitor ruxolitinib resulted in an augmentation of chemoresistance to crizotinib in the context of hypoxia. Overexpression of hypoxia-inducible factor 1 (HIF1) and silencing of JAK2 confirmed that the two proteins cooperate in mediating chemoresistance to crizotinib in CML cell lines. It is noteworthy that the compound 2-methoxy estradiol (2ME2), which is a metabolite of estradiol lacking estrogenic activity, has shown efficacy in reinstating the sensitivity of CML cells to crizotinib in the presence of hypoxic circumstances. Additionally, when used in conjunction with a JAK2 inhibitor, 2ME2 exhibited activity in restoring crizotinib sensitivity in CML cells. The findings of our study underscore the significance of selectively targeting elements of the HIF1α pathway in order to achieve total eradication of chronic myeloid leukemia (CML) cells.

Community engagement in climate action and adaptation planning is an essential prerequisite for overcoming existing and projected environmental injustices associated with the negative impacts of climate change. Diversity and inclusion of stakeholders are crucial for addressing equity both in the development and implementation of local climate plans. Our study attempts to evaluate and compare consideration of equity in climate action and climate adaptation plans of Michigan cities and its association with a diversity of stakeholders involved in the planning process. Data analysis is based on the content of eight municipal climate action and/or climate adaptation plans, related documents, and interviews with city planners along with community activists. Data derived from climate action and adaptation plans were also compared to the strategies outlined in the Tribal Climate Adaptation Menu, which integrates climate science and indigenous knowledge. The study concludes that municipalities that engage more diverse groups of stakeholders appear to be more attentive to social equity and more likely to offer specific climate action and adaptation measures focusing on vulnerable groups. Integration of indigenous knowledge could provide valuable insights for municipalities through collaboration with tribal communities and climate adaptation experts.

The impact of riparian wetlands on the cycling, retention and export of nutrients from land to water varies according to local environmental conditions and is poorly resolved in catchment management approaches. To determine the role a specific wetland might play in a catchment mitigation strategy, an alternative approach is needed to the high frequency and spatially detailed monitoring programme that would otherwise be needed. Here, we present a new approach using a combination of novel and well-established geochemical, geophysical and isotope ratio approaches. This was developed and tested against a 2-year high-resolution sampling programme in a lowland permeable wetland in the Lambourn catchment, UK. The monitoring programme identified multiple pathways and water sources feeding into the wetland, generating large spatial and temporal variations in nutrient cycling, retention and export behaviours within the wetland. This complexity of contributing source areas and biogeochemical functions within the wetland were effectively identified using the new toolkit approach. We propose that this technique could be used to determine the likely net source/sink function of riparian wetlands prior to their incorporation into any catchment management plan, with relatively low resource implications when compared to a full high frequency nutrient speciation and isotope geochemistry-based monitoring approach.