Natural host defensins, also sometimes termed antimicrobial peptides, are evolutionarily conserved. They have been studied as antimicrobials, but some pharmaceutical properties, undesirable for clinical use, led to the development of synthetic molecules with constructed peptide arrangements and/or peptides not found in nature. The leading development currently is synthetic small molecule nonpeptide mimetics, whose physical properties capture the characteristics of the natural molecules, and share their biological attributes. We studied brilacidin, an arylamide of this type, for its activity in vitro against fungi (40 clinical isolates, 20 species) that the World Health Organization has highlighted as problem human pathogens. We find antifungal activity at low concentrations for many pathogens, which indicates further screening for activity, particularly in vivo, is justified to evaluate this compound, and other mimetics, as attractive leads for development of effective antifungal agents.

Despite the growing capabilities of large language models, concerns exist about the biases they develop. In this paper, we propose a novel, automated mechanism for debiasing through specified dataset augmentation in the lens of bias producers that can be useful in a variety of industries, especially ones that are “restricted” and have limited data. We consider that bias can occur due to intrinsic model architecture and dataset quality. The two aspects are evaluated using two different metrics we created. We show that our dataset augmentation algorithm reduces bias as measured by our metrics.

Epilepsy is a common neurological condition, typically diagnosed using Electroencephalogram (EEG). Large scale EEG datasets have recently been made publicly available, allowing the use of advanced Machine Learning (ML) algorithms to analyze EEG patterns associated with epilepsy. While most existing studies focus on identifying seizures in the EEG, few have tried to identify preictal EEG segments. Identifying preictal EEG segments are not only useful in developing early warning systems but also helps inform the course of treatment for the patient. In this study, we propose to represent EEG segments as images, instead of time-series data, and identify preictal EEG segments using a preexisting ML algorithm (YOLOv8) designed for image processing. Multiplexed images (containing the original EEG signal represented on a 2D grid, kurtosis, and spectral entropy) achieve the best accuracy of 95.75% on the dataset while images just containing the EEG signal result in an accuracy of 91.25%. Using only spectrograms, generated from the original EEG signal, results in an accuracy of 90.15%.

This paper explores the suppression of ideas within academic scholarship by academics, either by self-suppression or because of the efforts of other academics. Legal, moral, and social issues distinguishing freedom of speech, freedom of inquiry, and academic freedom are reviewed. How these freedoms and protections can come into tension is then explored by an analysis of denunciation mobs who exercise their legal free speech rights to call for punishing scholars who express ideas they disapprove of and condemn. When successful, these efforts, which constitute legally protected speech, will suppress certain ideas. Real-world examples over the past five years of academics who have been sanctioned or terminated for scholarship targeted by a denunciation mob are then explored.

Both Stevens Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are main injurious cutaneous medication reactions that mostly affect the epidermis and mucus membranes. TEN and SJS affecting nearly 1 or 2/1,000,000 people per year, and can recognized as medical crises since they may be deadly. Mucocutaneous discomfort, hemorrhagic erosions, erythema, and more or less severe epidermal separation that appear as ulcer and patches of dermic loss are their defining characteristics. The sole difference between TEN and SJS at this time is the degree of skin detachment, making them two extremes of a spectrum of severe cutaneous adverse drug reactions (cADRs). In the majority of cases, drugs are considered as the principal reason of SJS/TEN, but herpes simplex virus and Mycoplasma pneumoniae infections are also recognized causes, along with lesser number of cases in which the cause is still unknown. Among the drugs with a "high" likelihood of producing TEN/SJS are carbamazepine (CBZ), trimethoprim-sulfamethoxazole, phenytoin, aminopenicillins, allopurinol, cephalosporins, other sulfonamide antibiotics, quinolones, phenobarbital, and NSAIDs of the oxicam variety. There is strong genetic evidence for SJS and TEN in Han Chinese due to the substantial association between the human leukocyte antigen (HLA-B*1502) and SJS brought on by CBZ. The diagnosis is made mostly based on clinical symptoms and the histological study of a dermal biopsy. Pemphigus vulgaris, bullous pemphigoid, linear IgA dermatosis, paraneoplastic pemphigus, disseminated fixed bullous drug eruption, acute generalized exanthematous pustulosis (AGEP), and staphylococcal scalded skin syndrome (SSSS) are among the differential diagnoses. The management of patients with SJS/TEN is complicated by the high risk of mortality, necessitating early diagnosis, estimation of the SCORTEN prognosis, identification and discontinuation of the causative drug, specialized supportive care, and high-dose injectable Ig therapeutic interventions. The reported fatality rates for SJS are 1-5% on average and 25-35% for TEN; it can be even higher in patients who are elderly or who have a significant amount of epidermal detachment on their skin. More than 50% of TEN patients who survive the disease experience long-term consequences.

Recent pollinator declines have focused efforts on their conservation which require clear estimates of pollination value to agriculture. Our socio-economic producer surveys and agronomic field research data were used to present a new way of estimating ecosystem service value of native pollinators. Using two regionally important U.S.A. crops, Maine wild blueberry and Massachusetts cranberry as models, we present perceived values of native bee pollinators from both consumer and producers. Wild blueberry’s Replacement Cost (RC) was greater than Attributable Net Income (ANI), since greater rented honey bee stocking densities are required. Attributable Net Income for native bees were similar for wild blueberry ($613/ha) and cranberry ($689/ha). Marginal Net Farm Income (MNFI) from incrementally adding more hives per ha was greater from stocking a third/fourth hive per ha for cranberry ($6,206) than stocking a ninth/tenth hive per ha for wild blueberry ($556), given greater responsiveness of yield, revenue, and profit to using rented honey bee hives in cranberry compared to wild blueberry. Both crops’ producers were only willing to annually invest $140–188/ha in native pollination enhancements on their farms, justifying government support. Consumers are willing to pay ~6.7 times more to support native bees than producers, supporting market-based support for invertebrate conservation.

Reducing under-five mortality is a key indicator of a country's overall development, yet in Angola, understanding the factors contributing to hospital deaths in this vulnerable demographic remains incomplete despite improvements in healthcare infrastructure and public health policies. With one of the highest under-five mortality rates in Sub-Saharan Africa, Angola grapples with significant challenges, including malaria, malnutrition, pneumonia, neonatal conditions, and intestinal infectious diseases, as leading causes of death among children. This study aimed to identify factors associated with these hospital deaths in children aged 28 days to five years admitted to DBPH in Luanda between May 2022 and June 2023. Utilizing a hospital-based case-control design, a total of 1020 children were studied, with 340 cases of hospital deaths. Notably, distal and intermediate determinants emerged as primary predictors of hospital mortality, revealing significant associations with maternal education status, maternal alcohol consumption during pregnancy, short hospital stays (≤24h), poor nutritional status, short interbirth intervals, maternal age ≤19 years, and maternal age ≥35 years. These findings underscore the preventable nature of most under-five hospital deaths and emphasize the urgent need to address social inequities and enhance the quality of primary healthcare services to effectively mitigate child mortality.

Life on Earth evolved to accommodate the biochemical and biophysical boundary conditions of the planet millions of years ago. The former includes nutrients, water, and ability to synthesize other needed chemicals. The latter include the 1 g gravity of the planet, radiation, and the geomagnetic field (GMF)of the planet. How complex life forms have accommodated the GMF is not known in detail considering that Homo sapiens evolved a neuro system and a cardiovascular system that develops electromagnetic fields as part of their functioning. In addition, many proteins and physiologic processes utilize Fe ions, an ion that exhibits magnetic properties. Thus, complex organisms such as current humans generate magnetic fields, contain significant quantities of the Fe ion, and also respond to exogenous-supplied static and electromagnetic fields. Whether humans can store information in self-generated magnetic fields remains to be determined. Given the current body of literature, it remains somewhat unclear how Homo sapiens use exogenous magnetic fields to regulate function, and what can happen if the boundary condition of the GMF of Earth is no longer exerting an effect. Proposed deep space flights to destinations such as Mars will provide some insights as space flight could not have been anticipated by evolution. The results of such space flight “experiments” will provide new insights in the role of magnetic fields on human functioning. The outcomes may also have implications for those on Earth as magnetic field influences may play a role in developmental conditions such as autism and senescence-associated conditions such as dementia when integration of the biological and biophysical aspects of humans of humans are required for effective functioning. This review will discuss the involvement of magnetic fields on various normal and disturbed processes in humans while on Earth and then further discuss potential outcomes when the GMF is no longer available to impact host systems. Thus, the GMF of the Earth has been present throughout evolution but details of its role in human functions still remain to be elucidated.

The ability to self-direct a research program determines graduate degree completion. Yet, research on incompletion of graduate physics programs assume students’ present level of self-direction adequate and neglects to recognize a lack of self-directed learning as key. One theoretical mathematical physicist focused on changing this challenge of physics graduate education by promoting self-directed learning through the type research flow that has been found to bring the greatest satisfaction to researchers with respect to their insights. This he provided through his space, time, open mindedness and theoretical contributions with his students and in collaboration with his colleagues. A self-directed learner himself, David J. Rowe developed methods of mentoring for encouraging physics graduate students to recognize symmetry as valuable in identifying solutions to problems quickly—helping these students take the lead in finding insightful resolutions to complex, multidimensional, mathematical physics uncertainties. How Rowe set about supporting self-directed learning in his graduate physics education interactions will be examined with the use of narrative research to interpret the texts and conversations with the author he made available. His techniques will be presented and recommendations made regarding how Rowe’s work in this regard can be modeled to improve self-direction in STEM graduate education.

The fact that individuals are spatially close to each other in the urban environment increases the potential number of encounters between them. Thus, theoretically speaking, the probability of interaction and social intercourse among people increases as they get closer to each other spatially. This reduction in spatial distance and propensity for larger networks can offer advantages in lower communication and transaction costs. However, there is also the possibility of entropy in a single (organizational) urban subsystem, characterized by reduced spatial distances between individuals that can lead to more toxic outcomes and the possibility of generalized deconstruction in an urban system as a whole. The current paper considers, through a theoretical model and secondary data analysis, how reductions in spatial distance between individuals in urban business organizations can lead to withdrawals of energy through toxic forms of entropic citizenship behavior, and lead to the development of toxic organizations. Such toxic organizations can ‘infect’ the urban system and lead to systematic entropic urban deconstruction. Practical, implications for management of the theoretical explanatory heuristic of toxic forms of organizational entropy and toxic organizations are briefly discussed in the paper.

Aim: Streptococcus pneumoniae and influenza H1N1 virus are common organisms associated with human infections. These infections could play a significant role in immune regulation. The study was performed to analyse the genome sequences of these organisms with human genome and study its functional significance. Methods: The study was performed to analyse the overlapping of genome sequences in Streptococcus pneumoniae and Influenza (H1N1) virus against human genome sequences by BLASTn sequence analysis. The alignments are studied against the corresponding genes for their functional significance with DAVID and NDEx software.Results: Several hits or overlapping nucleotide segments were identified. Between streptococcus and homo sapiens 287 overlaps were identified, and among influenza and homo sapiens 124 hits were identified. A wide range of functional significance of these genes were identified, and the results are presented in this study. The results show insights into functional pathways and biological activities associated with the respective vaccinations or infections by these microorganisms. Conclusion: The common organisms like Streptococcus pneumoniae and Influenza H1N1 virus actively interact with the immune system and result in a wide range of immune regulations.

Advances in the availability of multitemporal and global built-/human-settlements datasets as derived from Remote Sensing (RS) can now provide globally consistent definitions of “human-settlement” at unprecedented spatial fineness. Yet, these data only provide a time-series of past extents and urban growth/expansion models have not had parallel advances at high-spatial resolution. We present a flexible modelling framework for producing annual built-settlement extents in the near future past last observed extents as provided by RS-based data. Using a random forest and autoregressive temporal models with short time-series of built-settlement extents and subnational level data, we predict annual 100m resolution binary settlement extents five years beyond the last observations. We applied this framework within varying contexts and predicted annual extents from 2010 to 2015. We found that our model framework preformed consistently across all sample countries and, when compared to time-specific imagery, demonstrated the capacity to capture human-settlement missed by the input time-series and validation extents. When comparing building footprints of small settlements to forecast extents, we saw that the modelling framework had a 12 percent increase in ground-truth accuracy. This framework shows promise for predicting near-future settlement extents, and provides a foundation for forecasts further into the future.

In contrast to “frank” pathogens, like Salmonella entrocolitica, Shigella dysenteriae, and Vibrio cholerae, that always have a probability of disease, “opportunistic” pathogens are organisms that cause an infectious disease in a host with a weakened immune system and rarely in a healthy host. Historically, drinking water treatment has focused on control of frank pathogens, particularly those from human or animal sources (like Giardia lamblia, Cryptosporidium parvum, or Hepatitis A virus), but in recent years outbreaks from drinking water have increasingly been due to opportunistic pathogens. Characteristics of opportunistic pathogens that make them problematic for water treatment include: 1) they are normally present in aquatic environments, 2) they grow in biofilms that protect the bacteria from disinfectants, and 3) under appropriate conditions in drinking water systems (e.g., warm water, stagnation, low disinfectant levels, etc.) these bacteria can amplify to levels that can pose a public health risk. The three most common opportunistic pathogens in drinking water systems include Legionella pneumophila, Mycobacterium avium, and Pseudomonas aeruginosa. This report focuses on these organisms to provide information on their public health risk, occurrence in drinking water systems, susceptibility to various disinfectants and other operational practices (like flushing and cleaning of pipes and storage tanks). In addition, information is provided on a group of nine other opportunistic pathogens that are less commonly found in drinking water systems, including Aeromonas hydrophila, Klebsiella pneumoniae, Serratia marcescens, Burkholderia pseudomallei, Acinetobacter baumannii, Stenotrophomonas maltophilia, Arcobacter butzleri, and several free-living amoebae including Naegleria fowleri and species of Acanthamoeba. The public health risk for these microbes in drinking water is still unclear, but in most cases, efforts to manage Legionella, mycobacteria, and Pseudomonas risks will also be effective for these other opportunistic pathogens. The approach to managing opportunistic pathogens in drinking water supplies focuses on controlling the growth of these organisms. Many of these microbes are normal inhabitants in biofilms in water, so the attention is less on eliminating these organisms from entering the system and more on managing their occurrence and concentrations in the pipe network. With anticipated warming trends associated with climate change, the factors that drive the growth of opportunistic pathogens in drinking water systems will likely increase. It is important, therefore, to evaluate treatment barriers and management activities for control of opportunistic pathogen risks. Controls for primary treatment, particularly for turbidity management and disinfection, should be reviewed to ensure adequacy for opportunistic pathogen control. However, the major focus for the utility’s opportunistic pathogen risk reduction plan is the management of biological activity and biofilms in the distribution system. Factors that influence the growth of microbes (primarily in biofilms) in the distribution system include, temperature, disinfectant type and concentration, nutrient levels (measured as AOC or BDOC), stagnation, flushing of pipes and cleaning of storage tank sediments, and corrosion control. Pressure management and distribution system integrity are also important to the microbial quality of water but are related more to the intrusion of contaminants into the distribution system – rather than directly related to microbial growth. Summarizing the identified risk from drinking water, the availability and quality of disinfection data for treatment, and guidelines or standards for control showed that adequate information is best available for management of L. pneumophila. For L. pneumophila the risk for this organism has been clearly established from drinking water, cases have increased worldwide, and it is one of the most identified causes of drinking water outbreaks. Water management best practices (e.g., maintenance of a disinfectant residual throughout the distribution system, flushing and cleaning of sediments in pipelines and storage tanks, among others) that have been shown to be effective for control of L. pneumophila in water supplies. In addition, there are well documented management guidelines available for the control of the organism in drinking water distribution systems. By comparison, management of risks for Mycobacteria from water are less clear than for L. pneumophila. Treatment of M. avium is difficult due to its resistance to disinfection, the tendency to form clumps and attachment to surfaces in biofilms. Additionally, there are no guidelines for management of M. avium in drinking water and one risk assessment study suggested a low risk of infection. The role of tap water in the transmission of the other opportunistic pathogens is less clear and in many cases actions to manage L. pneumophila (e.g., maintenance of a disinfectant residual, flushing, cleaning of storage tanks, etc.) will also be beneficial in helping to manage these organisms as well.

Providing patient-centered care to manage chronic pain and opioid use disorder (OUD) is associated with improved health outcomes. However, adopting a holistic approach to providing care is often challenging in rural communities. This study aims to identify and contrast challenges to providing patient-centered care from the perspective of patients and providers. A participatory design approach was adopted to elicit the perceptions of providers and patients with lived experiences of chronic pain and OUD in Jefferson County, Wisconsin. Two focus groups were conducted with each stakeholder group to identify problems that participants face with respect to chronic pain management and OUD and possible solutions. Four interviews were conducted with providers experienced in chronic pain management. Analysis of focus group sessions and interviews show consensus among patients and providers that lack of behavioral health and recovery resources create barriers to effectively manage OUD and chronic pain. However, there was discordance among the two groups about other barriers such as patient and provider attitudes, tapering approach, and access to medications for OUD. This tension among patients and providers can influence patients’ retention in therapy. More efforts are needed to mitigate stigma among providers in rural communities and support psychosocial needs of patients.

Steel fibre reinforced concrete (SFRC) consists of short hooked steel fibres randomly distributed and oriented within the cementitious matrix. The contribution of fibre in bridging cracks to provide the stress transfer required relies upon the orientation of the fibre in the concrete. Bridging fibre aligned with a crack are less effective than those inclined to it. Therefore, understanding the pull-out behaviour of misaligned fibre is a key factor to quantify and optimize the design of SFRC in the structural applications. In the laboratory a single oriented fibre embedded in a solid cylinder of concrete is subjected to a pull-out test where the axis of a tensile force is aligned with the axis of the cylinder. Based upon the observed behaviour this paper presents a new analytical bounding approach to capture the pull-out response of misaligned hooked-end steel fibre embedded in a concrete matrix. The analysis is based upon a transversely isotropic condition assumed for the plasticity that occurs in the cold drawn fibre. The model accounts for the influence of fibre diameter and the combined strengths of the steel and concrete. The model predictions have also been compared with other experimental results published in the literature. The results showed that the model can predict pull-out loads reasonably for different fibre orientations between bounds of failure derived from the strengths of the two constituents. A critical orientation is observed at maximum strength. Therein, an understanding of the pull-out behaviour of misaligned, hooked-end fibres is necessary to optimize the strength of concrete from this method of reinforcement.

1) Background. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe mucocutaneous reactions, characterized by extensive necrosis and detachment of the epidermis. 2) Case presentation. We present a case of a 46-year-old patient with late-stage high-grade serous ovarian cancer who was primarily treated with neoadjuvant chemotherapy and interval debulking which was followed by adjuvant chemotherapy. At first recurrence, she was again treated with chemotherapy and due to severe abdominal pain, an elastomeric pump containing analgesics, anti-inflammatories and ondansetron was administered. In the same month, she was admitted to the hospital due to severe dysphagia and in the following days, she developed haemorrhagic vesiculobullous lesions on facial skin and trunk. Stevens-Johnson syndrome was confirmed and ondansetron as a leading cause was discontinued. Despite multimodal treatment, her condition deteriorated, and she died. 3) Discussion and conclusion. Although gynaecologists rarely encounter Stevens-Johnson syndrome, high mortality of the disease should ensure a low threshold for diagnosing and treating this disease.

Low- and middle-income country cities face unprecedented urbanization and growth in slums. Gridded population data in small grid squares (e.g., 100x100m) derived from demographic and spatial data are a promising source of current population estimates, but face limitations in slums due to the dynamic nature of this population as well as modelling assumptions. The efficacy of using gridded population data in slum areas remains a question mark especially in the context of UN SDG indicator development. In this study, we use field-referenced boundaries and population counts from Slum Dwellers International (SDI) in Lagos (Nigeria), Port Harcourt (Nigeria), and Nairobi (Kenya) to assess the accuracy of nine gridded population datasets in slums. We also use a modelled map of all slums in Lagos to assess use of gridded population dataset for SDG11.1.1 (percent of population living in deprived areas). We found that all gridded population estimates vastly under-estimated population counts in populous slums, and the calculation of SDG11.1.1 in Lagos was impossibly low; gridded population datasets estimated that just 1-3% of the Lagos population lived in slums, compared to 56% using the UN-Habitat approach. We outline specific steps that might be taken to improve each gridded population dataset in deprived urban areas. While gridded population estimates are not yet sufficiently accurate to estimate SDG11.1.1, we are optimistic that some datasets could be following updates to their modelling approaches.

The new logic of partitions is dual to the usual Boolean logic of subsets (usually presented only in the special case to the logic of propositions) in the sense that partitions and subsets are category-theoretic duals. The new information measure of logical entropy is just the normalized quantitative version of partitions. The new approach to interpreting quantum mechanics (QM) is showing that the mathematics (not the physics) of QM is the Hilbert space version of the mathematics of partitions. Or putting it the other way around, the math of partitions is a skeletal version of the math of QM. The key concepts throughout this progression from logic to information theory to quantum theory are distinctions versus indistinctions, definiteness versus indefiniteness, or distinguishability versus indistinguishability. The distinctions of a partitions are the ordered pairs of elements from the underlying set that are in different blocks of the partition. Logical entropy is defined (initially) as the normalized number of distinctions. The cognate notions of definiteness and distinguishability run through the math of QM, e.g., in the key non-classical notion of superposition (= ontic indefiniteness) and in the Feynman rules for adding amplitudes (indistinguishable alternatives) versus adding probabilities (distinguishable alternatives).

Personalized surgery is not just a new trend but rather a patient-specific approach to therapy that makes it possible to adopt a targeted approach for a specific patient and closely mirrors the approach of personalized medicine. However, the application of tailored surgery in the context of cardiovascular replacement surgery was not systematically reviewed. The ability to customize a device is highly dependent on the collection of radiological image data for precise prosthesis modelling. These facts are essential to "tailor-made" device design for precise prosthesis implantation. According to this study, computed tomography (CT) was the most prominent imaging modality; however, transoesophageal echocardiography and echocardiography were also found to be helpful. Additionally, a dynamic finite element simulation is also an attractive alternative to the finite element analysis for an in-silico experiment. Nonetheless, there is a paucity of relevant publications and sporadic evidence. More clinical studies have been warranted, notwithstanding that the derived data and results from the insight into the use of therapeutic interventions may be of multiple directives in clinical practices and beyond. This study may help the integration of personalized devices for better comprehending predicted clinical outcomes, thus leading towards enhanced performance gains.

For 80 years high-intensity focused ultrasound (HIFU) has been a significant area for medical research. It is a non-invasive procedure which causes cell death in a highly localised area at a defined distance from the transducer. Since 2000, the clinical indications have broadened considerable as the technology has improved. This review looks back at the history of HIFU and the current clinical indications.

A few empirical examples document fixed alternative male mating strategies in animals. Here we focus on the polymorphism of male mating strategies in the ruff (Calidris pugnax, Aves Charadriiformes). In ruffs, three fixed alternative male mating strategies coexist and are signaled by extreme plumage polymorphism. We first present relevant data on the biology of the species. Then we review the available knowledge of the behavioral ecology of ruffs during the breeding season and we detail the characteristics of each of the three known fixed male mating strategies. We next turn to the exceptional quality results accumulated on both the structural and functional genomics of the ruff over the past few years. We show how much these genomic data can shed a new, mechanistic light on the evolution and maintenance of the three fixed alternative male mating strategies. We then look if there are sufficient indication to support frequency-dependent selection as key mechanism in maintaining these three strategies. Specifically, we search for evidences of equal fitness among individuals using each of the three strategies. Finally, we propose three lines of research avenues that will help to understand the eco-evolutionary dynamics of phenotypic differences within natural populations of this iconic model species.

Nuclear protein of testis (NUT), a protein product of the NUTM1 gene (located on the long arm of chromosome 15) with highly restricted physiologic expression in post-meiotic spermatids, is the oncogenic driver of a group of emerging neoplasms when fused with genes involved in transcription regulation. Although initially identified in a group of lethal midline carcinomas in which NUT forms fusion proteins with bromodomain proteins, NUTM1-rearrangement has since been identified in tumors at non-midline locations, with non-bromodomain partners and with varied morphology. The histologic features of these tumors have also expanded to include sarcoma, skin adnexal tumors, and hematologic malignancies that harbor various fusion partners and are associated with markedly different clinical courses varying from benign to malignant. Most of these tumors have nondescript primitive morphology and therefore should be routinely considered in any undifferentiated neoplasm. The diagnosis is facilitated by the immunohistochemical use of the monoclonal C52 antibody, fluorescence in situ hybridization (FISH), and, recently, RNA-Sequencing. The pathogenesis is believed to be altered expression of oncogenes or tumor suppressor genes by NUT-mediated genome-wide histone modification. NUTM1-rearranged neoplasms respond poorly to classical chemotherapy and radiation therapy. Targeted therapies such as bromodomain and extraterminal domain inhibitor (BETi) therapy are being developed. This current review provides an update of NUTM1-rearranged neoplasms, focusing on the correlation between basic sciences and clinical aspects.

Abstract: Aedes aegypti were exposed to water treated with mosquitocidal chips containing the insecticide pyriproxyfen in a polymer formulation. Chips were tested under different conditions; different water volumes, in containers made of different material, and in water with different levels of organic matter. Treated chips caused 100% mortality of Ae. aegypti during their pupal stage independent of conditions chips were exposed to in water. When tested for longevity, the chips containing 840 µg of pyriproxyfen killed 100% of Ae. aegypti for 4 sequential months of the chips being reused in water. Chips containing 8.4 µg of pyriproxyfen ceased to work after the first week of treatment. When mosquitocidal chips were used in > 25% of the oviposition containers within their cages, there was a significant control of the mosquito populations. Mosquitocidal chips worked in different environments, lasted for extended periods of time, caused significant mosquito population decreases, and were effective in controlling Ae. Aegypti.

Fourteen (14) rack-mounted polycrystalline modules installed on the concrete roof of the solar energy applications laboratory at the Kwame Nkrumah University of Science and Technology (KNUST) in Ghana, a hot humid environment were assessed after 19 years of continuous outdoor expodure. The physical state of the modules was documented using a visual inspection checklist. They were further assessed by current-voltage (I-V) characterization and thermal imaging. The modules were found to be in good physical state, except some bubbles on front side and minor discolouration/corrosion at edge of the cells. Compared with reference values, the performance decline of the modules observed over the exposure period was: nominal power (P_nom), 21% to 35%; short circuit current (I_sc), 5.8% to 11.7%; open circuit voltage (V_oc) 3.6% to 5.6% and 11.9% to 25.7% for fill factor (FF). It is hoped that this study will provide some helpful information to project developers, manufacturers and the research community on the long-term performance of PV modules in Ghana.

People living in slums and other deprived areas in low- and middle-income country (LMIC) cities are under-represented in censuses, and subsequently in "top-down" gridded population estimates. Modelled gridded population data are a unique source of disaggregated population information to calculate local development indicators such as the Sustainable Development Goals (SDGs). This study evaluates if, and how, WorldPop-Global (WPG) -Unconstrained and -Constrained “top-down” datasets might be improved in a simulated realistic LMIC urban population by incorporating slum profile population counts into model training. We found that the WPG-Unconstrained model with or without slum training data grossly underestimated population in urban deprived areas while grossly overestimating population in rural areas. SDG 11.1.1, the percent of population living in slums, for example, was estimated to be 20% or less compared to a "true" value of 29.5%. The WPG-Constrained model, which included building auxiliary datasets, far more accurately estimated the population in all grid cells (including rural areas), and the inclusion of slum training data further improved estimates such that SDG 11.1.1 was estimated at 27.1% and 27.0%, respectively. Inclusion of building metrics and slum training data in “top-down” gridded population models can substantially improve grid cell-level accuracy in both urban and rural areas.

Viruses with spindle or lemon-shaped virions are rare in the world of viruses, but are common in viruses of archaeal extremophiles, possibly due to the extreme conditions in which they thrive. However, the structural and genetic basis for the unique spindle shape is unknown. The best-studied spindle-shaped virus, SSV1, is composed mostly of the major capsid protein VP1. Similar to many other viruses, proteolytic cleavage of VP1 is thought to be critical for virion formation. Unlike half of the genes in SSV1, including the minor capsid protein gene vp3, the vp1 gene does not tolerate deletion or transposon insertion. In order determine the role of the vp1 gene and its proteolysis for virus function, we developed techniques for site-directed mutagenesis of the SSV1 genome and complemented deletion mutants with vp1 genes from other SSVs. By analyzing these mutants we demonstrate that the N-terminus of the VP1 protein is required, but the N-terminus, or entire SSV1 VP1 protein, can be exchanged with VP1s from other SSVs. However, the conserved glutamate at the cleavage site is not essential for infectivity. Interestingly, viruses containing point mutations at this position generate mostly abnormal virions.

We discuss a remote sensing system that is used to simultaneously detect range-resolved differential absorption LIDAR (light detection and ranging; DIAL) signals and integrated path DIAL signals (IP-DIAL) from aerosol targets for ranges up to 22 km. The DIAL/IP-DIAL frequency converter consists of an OPO pumped at 1064 nm to produce light at 1.6 μm and operates at 100 Hz pulse repetition frequency. The probe light is free space coupled to a movable platform that contains one transmitter and two receiver telescopes. Hybrid photon counting/current systems increase the dynamic range for detection by two orders of magnitude. Range resolved and column integrated dry-air CO2 and CH4 mixing ratios are obtained from line shape fits of CO2 and CH4 centered at 1602.2 nm and 1645.5 nm, respectively and measured at 10 different frequencies over ≈ 1.5 cm-1 bandwidth. The signal-to-noise ratios (SNR) of the IP-DIAL returns from cloud aerosols approach 1000:1 and the uncertainties in the mixing ratios weighted according to the integrated counts over the cloud segments range from 0.1 % to 1 %. The range averaged DIAL mixing ratios are in good agreement with the IP-DIAL mixing ratios at the 1 % to 2 % level for both CO2 and CH4. These results can serve as a validation method for future active and passive satellite observational systems.

Foam concrete is a construction material with controllable low strength and untraditional physical properties. Its highly crushable nature leaves it a niche as an engineered energy-absorbing material in many value-added applications; however, fundamental understanding of the material properties is crucial. As foam concrete is highly cellularized and ductile, conventional concrete testing methods such as compression test are insufficient to characterize the key material attributes of foam concrete, especially when the foam density is low. The resonant frequency test (ASTM C215) is specified for evaluating dynamic Young’s modulus of normal concrete. Inspired by the non-destructive feature of this test, we investigate the possibility of using the resonant frequency test to continuously monitor the modulus build-up of foam concrete with age. For the representativeness of the samples, three variables are considered in material design—bulk density ranging from 0.4 to 1.2 g/cm3, water to cementitious materials ratio of 0.42 and 0.47, and fly ash replacement of 10 and 30% by weight of cement. After examining the different vibration modes, the fundamental transverse frequency is determined most suitable for interpreting the foam modulus. The experimental results demonstrate good accuracy of using this approach for the measurement of different samples. It is also confirmed that, for a given foam concrete, the foam modulus can be predicted by knowing the foam density and solid modulus of its base cement paste, which provides an important insight for the further studies and real applications of foam concrete.

The tiered laboratory framework for HIV viral load monitoring accommodates a range of HIV viral load testing platforms, with quality assessment critical to ensure quality patient testing. HIV plasma viral load testing is challenged by the instability of viral RNA. An approach using an RNA stabilizing buffer is described for the Xpert® HIV-1 Viral Load (Cepheid) assay and was tested in remote laboratories in South Africa. EDTA-plasma panels with known HIV viral titres were prepared in PrimeStore molecular transport medium for per-module verification and per-instrument external quality assessment. The panels were transported at ambient temperatures to 13 testing laboratories during 2017 and 2018, tested according to standard procedures and uploaded to a web portal for analysis. A total of 275 quality assessment specimens (57 verification panels and two EQA cycles) were tested. All participating laboratories met study verification criteria (n=171 specimens) with an overall concordance correlation coefficient (ρ_c) of 0.997 (95% confidence interval [CI]: 0.996 to 0.998) and a mean bias of -0.019 log cp/mL (95% CI: -0.044 to 0.063). The overall EQA ρ_c (n=104 specimens) was 0.999 (95% CI: 0.998 to 0.999), with a mean bias of 0.03 log cp/mL (95% CI: 0.02 to 0.05). These panels are suitable for use in quality monitoring of Xpert® HIV-1 VL and are applicable to laboratories in remote settings.

Over the last few decades, urban expansion and population shifts have modified the existing landscape throughout the U.S. Protected areas and development are compatible lenses, yet stakeholders’ involvement in decision-making is often missing from environmental governance. We examine how stakeholders living and working in proximity to Everglades National Park (EVER) perceive environmental and social changes to the park and community park relations. EVER was selected as a study site for several reasons: proximity to urban areas, rich biological diversity, largest subtropical wilderness in the U.S., International Biosphere Reserve, World Heritage Site, and prominence as a tourist destination for the region. Forty-one semi-structured interviews were conducted with neighborhood groups, representatives from gateway communities, and conservation organizations. An analysis of the interview data generated six research themes: loss of native species, urban development, a shortage and contamination of water, hurricanes, climate change, and increased recreation use. The results of this study add to the literature by providing a better understanding of the relationships stakeholders have with national parks. The results will provide useable knowledge that may help stakeholders and public land managers design strategies related for sustainable plans for the park and its surrounding communities.

The illicit use of fentanyl has led to hundreds of thousands of opioid-related deaths worldwide. Therefore, the detection of fentanyl by law enforcement and recreational users is of utmost importance. However, current detection methods are expensive, time-consuming, require special storage conditions and necessitate complex instrumentation that is generally unportable and requires skilled personnel to operate. An alternative approach would be using molecularly imprinted polymers (MIPs) as the recognition component of a handheld sensor, testing strip, or color-based assay. In this work, a molecularly imprinted polymer was made by using methacrylic acid (MAA) and ethyleneglycol dimethacrylate (EGDMA) as the functional monomer and cross-linking monomer respectively, and benzylfentanyl (Bfen) as the template. The use of benzylfentanyl is advantageous because it closely resembles the structure of fentanyl but does not have any physiological effects as a narcotic. Important studies herein determined the optimum ratio of the template:functional monomer, with subsequent evaluations of selectivity versus the commonly encountered narcotics such as heroin, cocaine, and methamphetamine. The data obtained from the HPLC analysis showed that the Bfen-MIP was successful in selectively binding the template and actual fentanyl, better than other common narcotics.

Information-related measures are useful tools for multi-variable data analysis, as measures of dependence among variables, and as descriptions of order and disorder in biological and physical systems. Measures, like marginal entropies, mutual / interaction / multi -information, have long been used in a number of fields including descriptions of systems complexity and biological data analysis. The mathematical relationships among these measures are therefore of significant inherent interest. Relations between common information measures include the duality relations based on Möbius inversion on lattices. These are the direct consequence of the symmetries of the lattices of the sets of variables (subsets ordered by inclusion). While these relationships are of significant interest there has been, to our knowledge, no systematic examination of the full range of relationships of this diverse range of functions into a unifying formalism as we do here. In this paper we define operators on functions on these lattices based on the Möbius inversions that map functions into one another (Möbius operators). We show that these operators form a simple group isomorphic to the symmetric group S₃. Relations among the set of functions on the lattice are transparently expressed in terms of the operator algebra, and, applied to the information measures, can be used to derive a wide range of relationships among diverse information measures. The Möbius operator algebra is naturally generalized which yields extensive new relationships. This formalism now provides a fundamental unification of information-related measures, and the isomorphism of all distributive lattices with the subset lattice implies an even broader application of these results.

Little in the scholarly economics literature is directed specifically to the performance of sta­ble value funds, although they occupy a leading place among retirement investment vehicles. They are currently offered in more than one-third of all defined contribution plans in the USA, with more than $800 billion of assets under management. This paper rigorously ex­amines their performance throughout the entire period since their inception in 1973. We produce a composite index of stable value returns. We next conduct mean-variance analysis, Sharpe and Sortino ratio analysis, stochastic dominance analysis, and optimal multi-period portfolio composition analysis. Our evidence suggests that stable value funds dominate (on average) two major asset classes based on a historical analysis, and that they often occupy a significant position in optimized portfolios across a broad range of risk aversion levels. We discuss factors that contributed to stable value funds’ past performance and whether they can continue to perform well into the future. We also discuss considerations regarding whether or not to include stable value as an element in target date funds within defined con­tribution pension plans.

Biochar application to soil has been proposed as a means for reducing soil greenhouse gas emissions and mitigating climate change. The effects, however, of interactions between biochar, moisture and temperature on soil CO₂ and N₂O emissions, remain poorly understood. Furthermore, the applicability of lab-scale observations to field conditions in diverse agroecosystems remains uncertain. Here we investigate the impact of a mixed wood gasification biochar on CO₂ and N₂O emissions from loess-derived soils using: (1) controlled laboratory incubations at three moisture (27, 31 and 35%) and three temperature (10, 20 and 30°C) levels, and (2) a field study with four cropping systems (continuous corn, switchgrass, low diversity grass mix, and high diversity grass-forb mix). Biochar reduced N₂O emissions under specific temperatures and moistures in the laboratory and in the continuous corn cropping system in the field. However, the effect of biochar on N₂O emissions was only significant in the field, and no effect on cumulative CO₂ emissions was observed. Cropping system also had a significant effect in the field study, with soils in grass and grass-forb cropping systems emitting more CO₂ and less N₂O than corn cropping systems. Observed biochar effects were consistent with previous studies showing that biochar amendments can reduce soil N₂O emissions under specific, but not all, conditions. The disparity in N₂O emission responses at the lab and field scales suggests that laboratory incubation experiments are not reliable for predicting the impact of biochar at the field scale.

Patients with chronic obstructive pulmonary disease (COPD) often require frequent hospitalization due to worsening symptoms. Preventing prolonged hospital stay and readmission becomes a challenge for healthcare professionals treating patients with COPD. Although the integration of health and social care supports greater collaboration and enhanced patient care, organizational structure and poor leadership may hinder the implementation of patient-oriented goals. This paper presents a case of a 64-year-old chronic smoker with severe COPD who was to be discharged on long-term oxygen therapy (LTOT). It further highlights the healthcare decisions made to ensure the patient’s safety at home and further provides a long-lasting solution to the existing medical and social needs. The goal was accomplished through a discharge plan that reflects multidisciplinary working, efficient leadership, and change management using Havelock’s theory. While COPD is characterized by frequent exacerbation and hospital readmission, it was emphasized that most failed discharges could be attributed to bureaucratic organizational workflow which might not be in the patient’s best interest. It was further demonstrated that healthcare professionals are likely to miss the window of opportunity to apply innovative and long-lasting solutions to the patient’s health condition in an attempt to remedy the immediate symptoms of COPD

The study combines two critical aspects of climate research in Nigeria. The first segment focuses on improving predictive performance of global circulation models (GCMs) employing ensemble techniques. ANN ensemble displayed significant improvement in the accuracy of climate projections, particularly in high-altitude geographic areas where traditional models exhibit limitations. Performance evaluation metrics such as Mean Absolute Error (MAE), Root Mean Squared Error (RMSE), and Nash–Sutcliffe Efficiency (NSE) demonstrate the effectiveness of the ANN multimodal ensemble. Building on the improved climate modelling, the second segment delves into a spatial and temporal analysis of rainfall and mean temperature patterns under climate change in Nigeria. By considering two Representative Concentration Pathways (RCPs), namely RCP4.5 and RCP8.5, the study utilizes dynamically downscaled GCMs obtained from the Coupled Model Intercomparison Project phase 5 (CMIP5). The Mann-Kendall test reveals significant spatiotemporal variations in climate trends across the country. The warming trend is particularly pronounced in the northern regions, with RCP8.5 showing more severe impacts compared to RCP4.5. This integrated approach not only highlights the importance of multimodal ensembles in climate modelling but also provides valuable insights into the spatial and temporal patterns of climate change to inform effective adaptation and mitigation strategies for Nigeria.

Quantum gravity theories rely on a minimal measurable length for their formulations, which clashes with the classical formulation of the uncertainty principle and with Lorentz invariance from general relativity. These incompatibilities led to the development of the generalized uncertainty principle (GUP) from string theories and its various modifications. GUP and covariant formulations of the uncertainty principle are discussed, together with implications for space-time quantization.

Adaptive radiations occur mostly in response to environmental variation through the evolution of key eco-morphological innovations that allow emerging species to occupy new ecological niches. However, rapid phenotypic evolution and the evolution of key novelties are likely to also occur when a couple or few species are engaged into narrow ecological interactions. To demonstrate coevolution is a difficult task; only elusive evidences confirm that coevolution is a driver of speciation and diversification. Here we propose that the adaptive radiation of the Mediterranean orchid genus Ophrys, which gave rise to ca. 350 species since the apparition of the genus is due to the particular co-evolutionary dynamics between these plants and their pollinators. We suggest that the pollination by sexual swindle used by Ophrys orchids is the main driver of this coevolution. Flowers of each Ophrys species mimic sexually receptive females of one particular insect species, mainly bees. Male bees are attracted by pseudo-pheromones emitted by Ophrys flowers that are similar to the sexual pheromones of their females. Males lured by the flower shape, color and hairiness attempt to copulate with the flower, which glues pollen on their bodies. Pollen is eventually transferred to the stigma of another flower of the same Ophrys species during similar copulation attempts. Three observations led us to propose the scenario of an asymmetric co-evolutionary relationship between Ophrys and their pollinators. Firstly, there is a strong intra-specific competition among Ophrys individuals for the attraction of their species-specific pollinators, which is due to the high learning and memorization abilities of bees that record the pheromone signatures of kin or of previously courted partner to avoid (further) copulation attempts. Mnemonic pollinators induce thus a strong selective pressure for variation in the pseudo-pheromones emitted by individual flowers, which will potentially generate shifts in pollinator species, and hence Ophrys speciation. These pollinator shifts are adaptive for new Ophrys species because they may benefit from a competitor-free space. Secondly, such shifts in pollinator species are due to the random crossing of peaks in the olfactory landscape of the pollinator guild that is syntopic to each particular Ophrys population. This selective process on individual, random variation in pseudo-pheromone bouquets is followed by directional selection on flower phenotypes that will reinforce the attraction of the new pollinator. Thirdly, pollinators use the pseudo-pheromones emitted by Ophrys to locate suitable habitats from a distance within complex landscapes. Pollinators stay fixed for a while in these habitats by the local diversity of pseudo-pheromones, which increases their probability of encounter with a receptive female and hence the reproduction probability of both sexes. Conversely, pollinators disperse out of small suitable habitats once they have memorized the local diversity of sexual pseudo-pheromone bouquet or if fecundated Ophrys flowers repel pollinators, which decreases the probability of geitonogamy (plant advantage) but limit pollinator mating with locally emergent insect females, thus limiting inbreeding and favoring gene flow (pollinator advantage). Finally, we propose several research avenues that emerged according to this scenario of adaptive radiation by assymetric coevolution between Ophrys species and their pollinators.

Bats are reservoirs of many pathogenic viruses including the lyssaviruses rabies virus (RABV) and Australian bat lyssavirus (ABLV). Lyssavirus strains are closely associated with particular host reservoir species, with evidence of specific adaptation. Associated phenotypic changes remain poorly understood but are likely to involve P protein, a key mediator of the intracellular virus-host interface. Here, we examine the phenotype of P protein of ABLV, which circulates as two defined lineages associated with frugivorous and insectivorous bats, providing the opportunity compare proteins of viruses adapted to divergent bat species. We report that key functions of P protein in interferon/STAT1 antagonism and the capacity of P protein to undergo nuclear trafficking differ between lineages. Molecular mapping indicates that these differences are functionally distinct, and appear to involve modulatory effects on regulatory regions or structural impact, rather than changes to defined interaction sequences. This results in partial but significant phenotypic divergence, consistent with ‘fine-tuning’ to host biology, and with potentially distinct properties in the virus-host interface between bat families that represent key zoonotic reservoirs.

Background: Symptomatic Pelvic Congestion Syndrome (PCS) is often underdiagnosed and undertreated. We investigate a symptoms-based screening algorithm and treatment algorithm focused on position and location of pain for each type of PCS. Methods: This study is a retrospective, single-institution, multi-site review of 343 female patients who presented with pelvic pain. Results: Following a symptoms-based algorithm, 302 patients fulfilled criteria for inclusion; 299 patients had positional symptoms with a positive predictive value (PPV) of 97.99%, sensitivity of 98.99% and Odds Ratio (OR) of 48.83 (p=0.0003) while duplex ultrasonography (DUS) had a PPV of 98.84%, sensitivity of 86.49%, and OR of 6.4 (p=0.0396) confirmed by contrast venography. Patients with Type I PCS were treated with embolization and 87.5% reported total relief of anterior symptoms. Patients with Type II PCS were treated with embolization and/or vascular stenting based on their associated lesion, May-Thurner syndrome or Nutcracker syndrome, and 88.54% reported ≥50% symptom relief and 59.03% reported ≥80% symptom relief. Full treatment resulted in a mean “overall satisfaction” score of 96.07%. Conclusions: Algorithmic approaches are essential for PCS evaluation, diagnosis, and treatment. Patients with positional pelvic symptoms consistent with PCS should undergo diagnostic venography. Distinguishing between the types of PCS and using symptoms as a guide may be beneficial over a “one-size-fits-all” approach.

Carbonaceous materials have gained significant attention in recent years for their various applications in the field of medicine and biotechnology. This comprehensive review explores the synthesis and characterization of carbon-based materials and their potentials in various medical applications. The paper delves into the methods of fabrication of carbon-based nanoparticles, such as carbon nanotubes, biochar, and graphene, while highlighting their unique properties. Characterization techniques, such as microscopy, spectroscopy, and surface analysis, are discussed to provide insights into the chemical and structural properties of these materials. Furthermore, the review examined their wide-ranging medical applications, encompassing tissue engineering, drug delivery, biosensing, and imaging, showcasing the versatility and promising contributions of carbonaceous materials in the healthcare industry. The review outlines the current challenges and prospects in the field, emphasizing the growing significance of carbon-based materials as valuable tools in advancing medical science and technology, as well as public health.

Traditionally it has been thought necessary to lose 2% of body mass due to dehydration, before functioning is disrupted, although recently adverse effects have been reported with a loss of 0.5-0.7%. It is, however, unclear whether the response to small decreases in mass reflects dehydration, mechanisms that help to adapt to a loss of bodily fluid, or a placebo effect. Individuals were therefore subject to a temperature of 30°C for three hours, and mood and cognition monitored. To explore the possibility of a placebo response, the consumption of plain or coloured water was compared. To consider changes in hydration status, drinks known to differ in their ability to rehydrate were contrasted. Not drinking was disruptive, although a combination of plain water and electrolyte’s most effectively prevented a decline in functioning, indicating a role for rehydration after a loss of 0.52% body mass. There was, however, also evidence of a placebo response: a combination of plain water and electrolytes was better able to prevent a decline in functioning than coloured plain water and electrolytes. As increased anxiety was a robust response, it was discussed whether the renin–angiotensin–aldosterone system might be part of the mechanism.

The windowpane oyster Placuna placenta, lives in brackish coastal waters and has long been economically important to the Philippines because of its durable and translucent shell, which is used as a glass substitute and material for making windowpanes and handicrafts. There has been considerable degradation of the windowpane oyster fishery in past decades. Moreover, there are waste and under-exploited by-products such as the meat, which though nutritious and edible, currently has a very low value; its use being confined to dishes consumed by families in the fishing community. Historically there are instances of excellent practice in terms of regulating the windowpane oyster fishery, while in recent times there have been local initiatives to restore this and to develop high value food products from the meat. These initiatives have, however, never been followed through at a provincial or national level. Research on other molluscs and marine organisms highlights that these also contain high value pharmaceutical products. This review compiles evidence to establish the groundwork for an essential and comprehensive multidisciplinary research program centred around the windowpane oyster, which would ensure a high value for all parts of the oyster, including those currently discarded. By fostering a sustainable and circular economy within this fishery sector and its associated industry, its economic value would be amplified. This is particularly important for oyster harvesters in the Philippines, who often find themselves at the economic ladder's lower rungs. By integrating the principles of a circular economy, this initiative would not only aim to uplift the economic prospects of these harvesters but in doing so would drive the restoration of the windowpane oyster to its former range.

Recent research has suggested that working memory training interventions may benefit children with Developmental Language Disorder (DLD). The current study investigated a short and engaging adaptive working memory intervention that targeted executive skills and aimed to improve both language comprehension and working memory abilities in children with DLD. Forty-seven 6- to 10-year-old children with DLD were randomly allocated to an executive working memory training intervention (n=24) or an active control group (n=23). A pre-test/intervention/post-test/9-month-follow-up design was used. Outcome measures included assessments of language (to evaluate far transfer of the training) and working memory (to evaluate near transfer of the training). Hierarchical multiple regression analyses controlling for pre-intervention performance and age found group to be a significant predictor of sentence comprehension and of performance on six untrained working memory measures at post-intervention and 9-month follow-up. Children in the intervention group showed significantly higher language comprehension and working memory scores at both time points than children in the active control group. The intervention programme showed potential to improve working memory and language comprehension in children with DLD and demonstrated several advantages: it involved short sessions over a short period; caused little disruption in the school day; and was enjoyed by children.

It is important to understand the statistical-physical structure of the rain in the vertical so that observations aloft can be translated meaningfully into what will occur at the surface. In order to achieve this understanding, it is necessary to gather high temporal and spatial resolution observations of rain in the vertical. This can only be accomplished using radars. It can be achieved by translating radar Doppler spectra into drop size distributions which can then be integrated to calculate variables such as the rain fall rate. A long-standing difficulty in using such measurements, however, is the problem of vertical air motion which can shift the Doppler spectra, and, therefore, significantly alter the deduced drop size distributions and integrated variables. In this work, we illustrate the improvement in measured rain structures using a new approach for removing the effect of mean vertical air motion. It is demonstrated that the new approach proposed here not only produces what appear to be better estimates of the rainfall rates, but, also as a consequence, provides estimates of the temporal and spatial regionally coherent updraft and downdrafts occurring in the precipitation. Furthermore, the technique is readily applicable to other radars especially those operating at non-attenuating frequencies.

The integration of diverse distributed generation (DG) units, encompassing both Renewable Energy Sources (RES) and non-RES technologies delves into voltage levels, current distributions, and power flows, aiming to optimize and effectively manage the distribution network. An RES-based DGs such as photovoltaic systems and wind turbines, alongside non-RES units like fuel cells and micro turbines. This study proposes a hybrid approach the Multi-Objective Genetic Algorithm - Grey Wolf Optimizer (MOGA-GWO). By merging the strengths of multi-objective genetic algorithms with the efficiency of the Grey Wolf Optimizer, this advanced algorithm seeks semi-optimal solutions for multi-objective optimization problems. The algorithm aims to improve convergence speed without compromising solution quality, offering a promising solution for optimizing the characteristics of DG and RES integration in distribution networks compared to Cuckoo Search and Simulation Annealing Techniques. Key algorithmic operations include individual representation, initialization, fitness function computation, selection, crossover, mutation, and ending conditions. The DG optimal power flow problem is explored with a focus on minimizing generation costs, improving voltage profiles, minimizing losses, enhancing reliability, integrating renewable energy, reducing environmental impact, managing congestion, and ensuring compliance with operational constraints. Beyond traditional considerations, the study emphasizes neglected objectives and constraints, such as cyber-security concerns, real-time operation, regulatory frameworks, social acceptance, lifecycle environmental impact, grid resilience, data privacy, aging infrastructure compatibility, and economic viability.

Immune responses to influenza (flu) antigens reflect memory to prior infections or vaccinations, which might influence immunity to new flu antigens. Memory of past antigens has been termed “original antigenic sin” or more recently “immune imprinting” and “seniority”. We have researched a comparison between the immune response to live flu infections and inactivated flu vaccina-tions. A brief history of antibody generation theories is presented culminating in new findings about the immune-network theory suggesting that a network of clones exists between an-ti-idiotypic antibodies and T cell receptors. Findings regarding the 2009 pandemic flu strain and immune responses to it are presented, including memory B cells and conserved regions within the hemagglutinin protein. The importance of CD4+ memory T cells and cytotoxic CD8+ T cells responding to both infections and vaccinations are discussed and compared. Innate immune cells like natural killer (NK) cells and macrophages are discussed regarding their roles in adaptive immune responses. Antigen presentation via macroautophagy processes are described. New vaccines in development are mentioned along with the results of some clinical trials. The manu-script concludes with how repeated vaccinations are impacting the immune system and a sketch of what might be behind the imprinting phenomenon, including future research directions.

Homelessness continues to be a pervasive public health problem throughout Canada. Hospital Emergency Departments (EDs) and inpatient wards have become a source of temporary care and shelter for homeless patients. Upon leaving the hospital, homeless patients are not more equipped than before to find permanent housing. The Bridge Healing Program in Edmonton, Alberta has emerged as a novel approach to addressing homelessness by providing transitional housing for those relying on repeated visits to the ED. This paper describes the three essential components to the Bridge Healing model: partnership between the ED and a Housing First community organization; facility design based on The Eden Alternative™ principles, and; grassroots community funding. This paper in conjunction with the current pilot project of the Bridge Healing facilities serves as a proof of concept for the model and can inform transitional housing approaches in other communities.

Vitamin D, unlike the micronutrients, vitamins A, E and K, is largely obtained, not from food, but by the action of solar UV light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Because no defined storage organ or tissue has been found for vitamin D, it has been assumed that adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D) which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into blood. This uptake and release of 25(OH)D by muscle, accounts for the very long half-life of this metabolite in the circulation. As 25(OH)D concentration in blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain adequate vitamin D status in winter.

Vitamin D, unlike the micronutrients, vitamins A, E and K, is largely obtained, not from food, but by the action of solar UV light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Because no defined storage organ or tissue has been found for vitamin D, it has been assumed that adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D) which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into blood. This uptake and release of 25(OH)D by muscle, accounts for the very long half-life of this metabolite in the circulation. As 25(OH)D concentration in blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain adequate vitamin D status in winter.

In a search for a reliable, inexpensive, and versatile technique for high-throughput kinetic assays of drug metabolism, we elected to rehire an old-school approach based on the determination of formaldehyde (FA) formed in cytochrome P450-dependent demethylation reactions. After evaluating several fluorometric techniques of FA detection, we choose the method based on the Hantzsch reaction with acetoacetanilide as the most sensitive, robust, and adaptable to high-throughput implementation. Here we provide a detailed protocol for the use of our new technique for automatized assays of cytochrome P450-dependent drug demethylations and discuss its applicability for high-throughput scanning of the pathways of drug metabolism in the human liver. To probe our method further, we applied it to re-evaluating the pathways of metabolism of ketamine, a dissociative anesthetic, and potent antidepressant increasingly used in the treatment of alcohol withdrawal syndrome. Probing the kinetic parameters of ketamine demethylation by 11 major cytochrome P450 (CYP) enzymes, we demonstrate that besides CYP2B6 and CYP3A enzymes, which were initially recognized as the primary metabolizers of ketamine, an important role is also played by CYP2C19, and CYP2D6, while the involvement of CYP2C9 suggested in the previous reports deemed insignificant.

Twelve wild North American Porcupines (Erethizon dorsatum) were diagnosed with dermatopathies while being cared for at two wildlife rehabilitation clinics. Biopsy and necropsy were performed on 7 and 5 animals respectively. Atypical dermatophytosis was diagnosed in all cases. Lesions consisted of diffuse severe epidermal hyperkeratosis and mild hyperplasia, with mild lymphoplasmacytic dermatitis, and no folliculitis. Dermatophytes were noted histologically as hyphae and spores in hair shafts, and follicular and epidermal keratin. Trichophyton sp. was grown in 5/6 animals where culture was performed, with molecular diagnosis of Arthroderma benhamiae / Trichophyton mentagrophytes in these 5 cases. Metagenomic analysis of formalin-fixed paraffin-embedded tissue samples from 3 cases identified fungi from 17 orders in phyla Basidiomycota and Ascomycota. Alteration of therapy from ketaconazole, which was unsuccessful in 4 of 5 early cases, to terbinafine or nitraconazole lead to resolution of disease and recovery to release in four subsequent animals. In all, 6 animals were euthanized or died due to dermatopathy, no cases resolved spontaneously, and 6 cases resolved with therapy. The work we present demonstrates an atypical lesion and anatomical distribution due to dermatophytosis in a series of free-ranging wild porcupines and successful development of novel techniques for extraction and sequencing nucleic acids from fungus in archival formalin-fixed paraffin-embedded animal tissue.

Background. The Stanford Health Assessment Questionnaire-Disability Index (HAQ) is widely used to measure functional ability in persons with Rheumatoid Arthritis (RA). The instrument was developed with limited involvement from persons with RA, and their perception of the instrument has not been studied in depth. The aim of this study was to explore how persons with RA experience the use of the HAQ in care. Methods. Forty persons with RA were purposefully recruited to participate in semi-structured interviews. The interviews were then analyzed qualitatively using thematic analysis. Results. The participants questioned the relevance of the HAQ but nevertheless experienced that the instrument had a profound effect on their understanding of health and how care is delivered. The analysis resulted in three themes: Problems with individual items, meaning of the summative score, and effects on care and health perceptions. Conclusions. To make the HAQ relevant to persons with RA, it needs to be revised or to include an option to select items most meaningful to the respondent. To ensure relevance, the HAQ update should preferably be co-created by researchers, clinicians and persons with RA.

Polycystic ovary syndrome (PCOS) is a common endocrinopathy of reproductive-aged women characterized by hyperandrogenism, oligo-anovulation and insulin resistance closely linked with preferential abdominal fat accumulation. As an ancestral primate trait, PCOS was likely further selected in humans when scarcity of food in hunter-gatherers of the late Pleistocene additionally programmed for enhanced fat storage to meet the metabolic demands of reproduction in later life. As an evolutional model for PCOS, healthy normal-weight women with hyperandrogenic PCOS have subcutaneous (SC) abdominal adipose stem cells that favor fat storage through exaggerated lipid accumulation during development to adipocytes in vitro. In turn, fat storage is counterbalanced by reduced insulin sensitivity and preferential accumulation of highly-lipolytic intra-abdominal fat in vivo. This metabolic adaptation in PCOS balances energy storage with glucose availability and fatty acid oxidation for optimal energy use during reproduction; its accompanying oligo-anovulation allowed PCOS women from antiquity sufficient time and strength for childrearing of fewer offspring with a greater likelihood of childhood survival. Heritable PCOS characteristics are now affected by today’s contemporary environment through epigenetic events that predispose to lipotoxicity with excess weight gain and pregnancy complications, calling for an emphasis on preventive healthcare to optimize the long-term, endocrine-metabolic health of PCOS women in today’s obesogenic environment.

The severity and outcome of coronavirus disease 2019 (COVID-19) largely depends on a patient’s age. Over 80% of hospitalizations are of those over 65 years of age with a 23-fold greater risk of death. In the clinic, COVID-19 patients most commonly present with fever, cough and dyspnea. Particularly in those over 65, it can progress to pneumonia, lung consolidation, cytokine release syndrome, endotheliitis, coagulopathy, multiple organ failure and death. Comorbidities such as cardiovascular disease, diabetes, obesity and hypertension increase the chances of fatal disease, but they alone do not explain the variability in COVID-19 symptoms. Here, we present the molecular differences between the young, middle-aged and elderly that may determine whether COVID-19 is a mild or life-threatening illness. We also discuss several biological age clocks that could be used in conjunction with genetic tests to identify both the mechanisms of the disease and individuals most at risk. Finally, based on these mechanisms, we discuss treatments that could increase survival in the elderly, not simply by inhibiting the virus, but by restoring patients’ ability to clear the infection.

Viruses frequently contain overlapping genes, which encode functionally unrelated proteins from the same DNA or RNA region but in different reading frames. Yet overlapping genes are often overlooked during genome annotation, in particular in DNA viruses. Here we looked for the presence of overlapping genes likely to encode a functional protein in human parvovirus B19 (genus erythroparvovirus), using an experimentally validated software, Synplot2. Synplot2 detected an open reading frame, X, conserved in all erythroparvoviruses, which overlaps the VP1 capsid gene, and is under highly significant selection pressure. In a related virus, human parvovirus (genus tetraparvovirus), Synplot2 also detected an open reading frame under highly significant selection pressure, ARF1, which overlaps the VP1 gene. X and ARF1 have exactly the same location (both overlap the region of VP1 encoding the phospholipase A2 domain), and encode proteins with similar predicted properties, such as a transmembrane region, strongly suggesting that they are homologous. These findings provide compelling evidence that the X protein must be expressed and functional. It is probably translated either from a polycistronic mRNA by a non-canonical mechanism, or from an unmapped monocistronic mRNA. Finally, we also discovered proteins predicted to be expressed from a frame overlapping VP1 in other species related to parvovirus B19: porcine parvovirus 2 (Z protein) and bovine parvovirus 3 (X-like protein).

Coronavirus disease 2019 (COVID-19) was initially characterized as a respiratory illness. Neurological manifestations were reported mostly in severely affected patients. Routes for brain infection and the presence of virus particles in situ have not been well described, raising controversy about how the virus causes neurological symptoms. Here, we report the autopsy findings of a 1-year old infant with COVID-19. In addition to pneumonitis and multiple organ damage related to thrombosis, SARS-CoV-2 infected the choroid plexus, ventricles, and cerebral cortex. This is the first evidence of SARS-CoV-2 detection in an infant post-mortem brain.

SARS-CoV-2 is a novel betacoronavirus and the aetiological agent of the current COVID-19 outbreak that originated in Hubei Province, China. While polymerase chain reaction is the front-line tool for SARS-CoV-2 surveillance, application of amplification-free and culture-free methods for isolation of SARS-CoV-2 RNA, partnered with next-generation sequencing, would provide a useful tool for both surveillance and research of SARS-CoV-2. We here release into the public domain a set of bait capture hybridization probe sequences for enrichment of SARS-CoV-2 RNA from complex biological samples. These probe sequences have been designed using rigorous bioinformatics methods to provide sensitivity, accuracy, and minimal off-target hybridization. Probe design was based on existing, validated approaches for detecting antimicrobial resistance genes in complex samples and it is our hope that this SARS-CoV-2 bait capture platform, once validated by those with samples in hand, will be of aid in combating the current outbreak.

Variant H3.3, along with H2A.Z, is notably enriched at promoter regions and is commonly associated with transcriptional activation. However, the specific molecular mechanisms through which H3.3 influences chromatin dynamics at transcription start sites, and its role in gene regulation, remain elusive. Using a combination of biochemistry and cryo-electron microscopy (cryo-EM), we show that the inclusion of H3.3 alone does not induce discernible changes in nucleosome DNA dynamics. Conversely, the presence of both H3.3 and H2A.Z enhances DNA flexibility similarly to H2A.Z alone. Interestingly, our findings suggest that the presence of H3.3 in the H2A.Z nucleosome provides slightly increased protection to DNA near the superhelical location (SHL) -5.5/5.5. These results imply that while H2A.Z at active promoters promotes the formation of more accessible nucleosomes with increased DNA accessibility to facilitate transcription, the simultaneous presence of H3.3 offers an additional mechanism to fine-tune nucleosome accessibility and the chromatin environment.

Technological advances in the last decades have led to the realization of the concept of a smart environment. A significant part of this development is decentralized ledger technology and its variant, a blockchain. The blockchain database is immutable, open to all stakeholders, secure by architecture and robust. Applying a blockchain in water supply sanitary control creates opportunities for optimization, higher quality of service, cost reduction, better sanitary standards and public control. Physical, chemical, and biological water supply contamination is a great source of public health hazards. Implementation of a blockchain for water supply IoT, from the source point to the consumption point, enables effective response to changing environments, possible cross-contamination, stormwater management or disaster and emergency action. The chapter encompasses all fundamental elements and principles of water collection, distribution and consumption, with a focus on the health hazards and sanitary requirements for potable water. The chapter listed the main contaminants, methods of their registration and elimination, and requirements for drinking water in accordance with WHO, EU Drinking Water Directive and EPA standards. Blockchain technology solutions are described for smart water supply, including smart supply management, smart contracts, tokenization, smart compliance systems, and, most importantly, effective utilization of distributed ledger technologies for sanitary monitoring of water sources, water treatment, and water distribution systems.

Rare Earth Elements (REE), also known as Lanthanides (Ln3+), are a group of 17 elements showing peculiar physical and chemical properties. Unlike technological applications, very little is known about the physiological role and toxicity of Ln3+ on biological systems, in particular on microorganisms (e.g., bacteria), which represent the most abundant domains on our planet. Up to now, very limited studies have been conducted due to Ln3+ precipitation with some anions commonly present in the culture media. Therefore, the development of a minimal medium is essential to allow the study of Ln3+-microbial interactions, limiting considerably the precipitation as insoluble salts. In this regard, a new minimal culture medium capable of solubilizing large amounts of Ln3+, and allowing the growth of different microbial taxa, was successfully developed. Assays have shown that the medium is capable of solubilizing Ln3+ up to 100 times more than other common culture media and allowed the growth of 63 bacteria and 5 fungi. The kinetic growth of one yeast and one gram-positive bacterium has been defined, proving to support superior growth and biomass compared to other commonly used minimal media. Moreover, the sensitivity and uptake/absorption of a Bacillus stratosphericus strain was tested, highlighting its capability to tolerate concentrations up to 10 mM of either Cerium, Gadolinium or Lanthanum and accumulate different quantities of the three.

Psychomotor developmental delay in infants includes failure to acquire abilities such as sitting, walking, grasping objects and communication at the ages when most infants have acquired these abilities. Known risk factors include a large number of aspects of family environment, socioeconomic position, problems in pregnancy and birth, and maternal health. It is clinically useful to be able to screen for developmental delay so that healthcare interventions can be considered. The present research used machine learning (random forest) to create an algorithm predicting psychomotor delay in 9-month-old infants using information ascertainable at birth and in early infancy. The dataset was the UK longitudinal Millennium Cohort study. Fifty-two predictors measuring socioeconomic indicators, paternal, family and social support for the mother, beliefs about good parenting, maternal health, pregnancy and birth were included in the initial algorithm. Feature reduction showed that of the 52 variables, birthweight, family income and parents’ ages had the highest feature importance scores and could alone correctly predict developmental delay with over 99% sensitivity and 100% specificity. The relationships between delay and some of the predictors, particularly income, were nonlinear and complex. The results suggest that the risk of psychomotor developmental delay can be identified in early infancy using machine learning, and that the best predictors are factors present prior to birth. Surprisingly, the most important factors included in the present study did not include illnesses during pregnancy such as eclampsia and infections.

Many models with structures of matter associated with a structure of extra spatial dimensions have been proposed in recent decades. On employing a further generalisation from the local 4-dimensional spacetime form to a general form for proper time, we describe how matter fields resembling the Standard Model of particle physics can be accommodated far more directly than with a higher-dimensional spacetime theory. The successful identification of key features of visible matter in this non-spatial sector of extra dimensions in turn motivates seeking a candidate for dark matter residing in the original extra spatial dimension sector, and provides a close guide for the explicit form this invisible matter might take. We describe how such Standard Model and dark matter sectors in different extra-dimensional branches of generalised proper time are gravitationally connected through their common root in the local 4-dimensional spacetime and consider further possible mutual interactions and implications in comparison with existing dark matter models. A yet further possible branch of generalised proper time can be connected with dark energy models, hence in principle accounting for all three major components of cosmological structure within this framework.

Proposed fundamental laws of biology and a model of health and disease underscore the importance of the lymphatic system. The lymphatics are responsible for two of the laws of biology and the fulcrum of health and disease balancing proliferation with regeneration through the immune system. It is responsible for protection from the environment and repair of senile and damaged tissue. Life is constantly bombarded by forces that increase entropy. Lymphatics provide negative entropy to maintain health. Lymphatics help maintain cellular homeostasis removing products of metabolism. Using these principles, the role of lymphatics is investigated in salt sensitivity hypertension, cardiorenal system, the new pillar of heart failure and kidney disease - Sodium-Glucose Transport Protein 2 (SGLT2) Inhibitors, and brain diseases. The realization of organ lymphatics in maintenance of health and disease opens the avenue to new therapeutics. This is the unrealized potential of lymphatic study.

Since the turn of the 21^st Century Chian has enacted a range of policies to improve its water ecosystem. Some of these measures include (but are not limited to) the creation of Seven River Conservancy Commissions to engage in river basin management and the development (combination and recombination) of series of ministries and departments to address environmental pollution and degradation. The most recent attempt to address the nations polluted waterways and lakes occurred in December 2016, when the General Office of the Chinese Central Committee and the State Council issued The Options on Full Implementation of the River Chief System (RCS) Across the Country. The intent behind Options was not only to fully implemented he river chief system but to bring the nations drinking water supply quality to no worse than category III. Based on the Options Erik Solheim, UN Under Secretary General and Executive Director of the UN Environment Programme, commented ‘I'm convinced that what I have seen in Pujiang County and Anji County will be the future of China, even the future of the world’ (cited in Xianqiang 2021, 435; emphasis added). It is to this observation that the reminder of this article will be directed.

An increasing global aridification due to climate change has made the health monitoring of vegetation indispensable to maintaining the food supply chain. Cost-effective and smart irrigation systems are required not only to ensure the efficient distribution of water, but also to track the moisture of plant leaves, which is an important marker of the overall health of the plant. This paper presents a novel electromagnetic method to monitor the water content (WC) and characterization in plant leaves utilizing the absorption spectra of water molecules in the terahertz (THz) frequency for four consecutive days. We extracted the material properties of leaves of eight types of pot herbs from the scattering parameters, measured using a material characterization kit in the frequency range of 0.75 to 1.1 THz. From the computed permittivity, it is deduced that the leaf specimens increasingly become transparent to the THz waves as they dry out with the passage of days. Moreover, the loss in weight and thickness of leaves were observed due to the natural evaporation of leaf moisture cells and change occurred in the morphology of fresh and water-stressed leaves. It is also illustrated that loss observed in WC on day 1 was in the range of 5\% to 22\%, and increased from 83.12\% to 99.33\% on day 4. Furthermore, we observed an exponential decaying trend in the peaks of the real part of the permittivity from day 1 to 4, which was reminiscent of the trend observed in the weight of all leaves. Thus, results in paper demonstrated that timely detection of water stress in leaves can help to take proactive action in relation to plants health monitoring, and for precision agriculture applications, which is of high importance to improve the overall productivity.

Field of ResearchThis research study investigates the role of distributed leadership and culture within small enterprises in Malta, an area in which there has been very limited research. It focuses on the interaction between these two elements and their impact on organizational behaviour and effectiveness. Several studies (Jardon et al 2019; Cope et al., 2011; de Oliveira et al., 2015; Mohanty et al., 2012;) suggest that effective leadership and culture are vital elements in the successful endeavours of small organizations. Schein (2006) further asserts that they are two different faces on the same coin and the dyadic interaction characterizes “how leaders create culture and how culture defines and creates leaders”. Distributed Leadership is a systematic practice of interactions and synergies between leaders, followers, and the situation (Spillane 2013). It is different from traditional leadership, which involves top-down management because it tends to be more democratic and participatory, whereby influence and decision-making are shared among multiple individuals rather than being controlled by a single leader. (Xhemajli et al. 2022) MethodologyAdopting a naturalistic approach and guided by an interpretivist, constructivist epistemological stance, this research delves into the intricate interplay between leadership and culture within small businesses. The chosen research methodology employs Grounded Theory, recognized for its robust and systematic process facilitating the observation of patterns through intensive iterative and highly analytical procedures (Charmaz, 2015).In the initial stages of field research, characterized by 'responsive interviewing' (Rubin and Rubin, 2012), data sampling commenced with convenience sampling. This initial phase gradually evolved into a refined strategy incorporating selective sampling and theoretical sampling (Corbin and Strauss, 2015). The shift in sampling approaches reflects a deliberate focus on collecting data based on its specific contribution to the development and comprehension of the dimensions, properties, and characteristics of key concepts.The induction of theory is a product of successive comparative analyses, involving the systematic comparison of data points to identify both similarities and variations. Abductive reasoning is integral throughout the analytical process, with particular emphasis during constant comparative analysis of categories, leading to theoretical integration (Charmaz, 2006). This meticulous approach aligns with the assertion of Strauss and Corbin (2015) that grounding theory in data enhances the likelihood of deriving theories that authentically reflect reality.The key advantage of using this approach is that the analysis carried out goes beyond deep exploration and rich description and actually develops a framework that explains the phenomena observed (Parker and Roffey, 1997, p.218). This is very important if the findings are to contribute to the knowledge enhancement of any field of practiceThe culmination of this research effort is the presentation of a set of interconnected concepts, intricately woven together into an emergent parsimonious model (Corbin and Strauss, 2015). This model serves to explain the dynamic interplay between leadership and culture, elucidating its tangible impact on the effectiveness of small enterprises. Research Contribution:Implications for PracticeThis research contributes to the literature on leadership and organizational culture in small enterprises, particularly in the context of Malta where such studies are scarce. By providing an initial exploration of these phenomena and their impact on organizational behavior, this paper lays the groundwork for further inquiry into this important area. Furthermore, the study offers practical insights for leaders of small enterprises by elucidating leadership behaviors observed in established organizations. Through applied cases, it demonstrates how the abstract concept of culture can be translated into a practical instrument that supports leadership and organizational development. This not only enriches the understanding of leadership dynamics but also provides tangible strategies for implementation. Moreover, the research contributes empirical evidence on the development of leadership functions within small enterprises, emphasizing the potential of shared and distributed leadership models. By grounding its findings in data, the study equips leaders with a deeper understanding of how these leadership approaches can shape organizational development, fostering more effective management practices in small businesses. Methodologically, the adoption of Grounded Theory methodology showcases its efficacy in exploring complex management phenomena. By employing this approach, the researchers were able to gather rich descriptions and develop an explanatory framework, highlighting its applicability in studying nuanced organizational dynamics. Implications for Policy and TheoryThis research also holds significant implications for policymakers, academic researchers and institutions involved in supporting small businesses. By providing insights into distributed leadership and cultural influences on organizational effectiveness, it offers a basis for informed policy formulation and support mechanisms. The conceptual model emerging from this study serves as a foundation for designing more targeted policies that cater to the unique needs of small enterprises. By understanding the intricacies of leadership dynamics and cultural contexts, policymakers can develop interventions that foster a conducive environment for small business growth and sustainability. Additionally, academic researchers can use these findings to further refine theoretical frameworks and empirical studies in the field, contributing to ongoing scholarly dialogue and knowledge advancement.

The construction sector of the Kingdom of Saudi Arabia (KSA), valued at USD 152 billion and employing 2.54 million people by 2023, is crucial to its economy. However, it faces challenges such as delays, disputes, and cost overruns. This study aims to address these issues by implementing Building Information Modeling (BIM) in the KSA, based on an extensive literature review highlighting the role and significance of BIM in mitigating construction claims. BIM improves collaboration, communication, and data integration among stakeholders. Hence, this study proposes a comprehensive BIM package framework comprising Revit Architecture, Microsoft Project, and Cost-X to reduce claims effectively. Validated through a KSA claims case study with a USD 1,870,000 claims value and 360-day delay, the BIM package significantly reduced the claims value to USD 188,000 and saved 275 days. Interview sessions were conducted to validate the effectiveness of the BIM package; 95% favored the use of BIM, 86% supported NEC4 contract adoption alongside BIM, 100% acknowledged BIM's potential in reducing design errors, 95% were confident in the case study's accuracy, and 82% were satisfied with data accuracy. This study confirms that BIM is an effective approach for minimizing construction claims in the KSA.

Three-quarters of a million babies are born extremely preterm (< 28 weeks’ gestation) world-wide with devastating outcomes: 20% die in the newborn period, a further 35% develop bronchopul-monary dysplasia (BPD) and 10% suffer from cerebral palsy. Pioglitazone, a Peroxisome Proliferator Activated Receptor Gamma (PPARγ) agonist, may reduce the incidence of BPD and improve neurodevelopment in extreme preterm babies. Pioglitazone exerts an anti-inflammatory action mediated through Nuclear Factor-kappa B repression. PPARγ signalling is underactive in preterm babies as adiponectin remains low during the neonatal pe-riod. In newborn animal models, pioglitazone is shown to be protective against BPD, necrotising en-terocolitis, and lipopolysaccharide-induced brain injury. Single Nucleotide Polymorphisms of PPARγ are associated with inhibited preterm brain development and impaired neurodevelop-ment. Pioglitazone was well tolerated by the foetus in reproductive toxicology experiments. Bladder cancer, bone fractures, and macular oedema seen rarely in adults may be avoided with a short treatment course. Other effects of pioglitazone including improved glycaemic control and lipid metabolism may provide added benefit in prematurity. Currently, there is no formulation of pioglitazone suited for administration to preterm babies A liquid formulation of pioglitazone needs to be developed before clinical trials. The potential benefits are likely to outweigh any anticipated safety concerns.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) continues to be a global threat due to its ability to evolve and generate new subvariants, leading to new waves of infection. Additionally, other coronaviruses like Middle East respiratory syndrome coronavirus (MERS-CoV, formerly known as hCoV-EMC) which first emerged in 2012, persists and continues to present a threat of severe illness to humans. The continued identification of novel coronaviruses, coupled with the potential for genetic recombination between different strains, raises the possibility of new coronavirus clades of global concern emerging. As a result, there is a pressing need for pan-CoV therapeutic drugs and vaccines. After extensive optimization of an HCV protease inhibitor screening hit, a novel 3CLPro inhibitor (MK-7845) was discovered and subsequently profiled. MK-7845 exhibited nanomolar in vitro potency with broad spectrum activity against a panel of clinical SARS-CoV-2 subvariants and MERS-CoV. Furthermore, when administered orally, MK-7845 demonstrated a notable reduction of viral burdens by &gt;6 log orders in the lungs of transgenic mice infected with SARS-CoV-2 (K18-hACE2 mice) and MERS-CoV (K18-hDDP4 mice).

Mallios and Zafiris emphasize that adjoint functors or adjunctions are not only "ubiquitous" in category theory but characterize the naturality of their approach to physical geometry. Hence in this paper, the history and theory of adjoint functors is investigated. Where do adjoint functors come from mathematically and how did the concepts develop historically?

Key elements of Blue-Green Infrastructure are vegetation and stormwater storage. A combination of a bioretention cell with an underlying trench (BC-T) serving as a tree pit is often used in dense urban environments. An adequate ratio of drained area to bioretention cell area is a crucial design parameter. The ratio is derived from the hydrological balance; however, input data are often difficult to obtain or uncertain. The goal is to study the sensitivity of such data (tree water uptake and water holding capacities of soil filter and trench substrate) in the BC-T design. Sensitivity analysis is performed for the setup of a BC-T used in Prague, Czech Republic. A 10-year rainfall series (1 hour resolution) is used as an input. Data that are subject to the sensitivity analysis are changed for different trench exfiltration rates, and the effect on the size of the drained area is studied. At low trench exfiltration rates (1.8 mm.h-1), both the water holding capacity of the trench substrate and potential tree water uptake have a significant influence (more than a 20% change in the size of the drained area) and cannot be neglected. At good exfiltration rates (more than 18 mm.h-1) or when the trench is equipped with an underdrain, all studied parameters can be neglected. However, it is recommended to reduce the size of the drained area by 10-20%.

Organic soil amendments, such as composts, mitigate the environmental burdens associated with wasting organic resources. Although compost application to soil enhances an agroecosystem's capacity to store carbon and produce food, studies investigating the agronomical efficacy and their ability to ameliorate drought stress when used as a soil amendment are minimal. In this study, we produced and used a nutrient rich co-compost through the composting of sludge, a nitrogen-rich organic material with carbon rich municipal solid wastes (MSW) to evaluate the agronomic efficacy of the MSW derived co-compost and their ability to ameliorate drought stress. Application of co-compost significantly enhanced growth and yield of lettuce and maize, by a magnitude comparable to chemical fertilizers. Furthermore, under drought stress, lettuce plants grown under co-compost soil amendment grew much better with less wilting, more biomass and yield, and improved root growth. Also, co-compost application enhanced relative root mass ratio (RRMR) under drought stress, indicative that co-compost amendment increased the allocation of biomass to the roots, which is an important morphological attribute for drought adaptability. K content in both leaves and roots of plants amended with co-compost was also higher under drought stress, which may have played a role in osmotic adjustment, consequently, the plants exhibited higher leaf relative water content (RWC). Other nutrient elements that were significantly enhanced by co-compost application included Mg, Ca, Fe and Cu. These results provide evidence that MSW co-composting could optimize organic resource recycling for climate change mitigation and agricultural productivity while minimizing nutrient losses from agroecosystems.

Current antibiograms cannot discern the particular effect of a specific antibiotic when the bacteria are incubated with a mixture of antibiotics. To prove that this task is achievable, Escherichia coli strains were treated with ciprofloxacin for 45 min, immobilized on a slide and stained with SYBR Gold. In susceptible strains, the nucleoid relative surface started to decrease near the MIC, being progressively condensed as dose increased. The shrinkage level correlated with the DNA fragmentation degree. Ciprofloxacin-resistant bacilli showed no change. Additionally, E. coli strains were incubated with ampicillin for 45 min and processed similarly. The ampicillin-susceptible strain revealed intercellular DNA fragments that increased with dose, unlike the resistant strain. Co-incubation with both antibiotics revealed that ampicillin did not modify the nucleoid condensation effect of ciprofloxacin, whereas the quinolone partially decreased the background of DNA fragments induced by ampicillin. Sixty clinical isolates, with different combinations of susceptibility-resistance to each antibiotic, were co-incubated with the EUCAST breakpoints of susceptibility of ciprofloxacin and ampicillin. The morphological assay correctly categorized all the strains for each antibiotic in 60 min, demonstrating the feasible independent evaluation of a mixture of quinolone and beta-lactam. The rapid phenotypic assay may shorten the incubation times and necessary microbial mass currently required for evaluation.

Organisms are adapted to each other and the environment, not as tradition would have it, because natural selection made them that way, but because there is inbuilt striving towards stability and equilibrium. A General Theory of Behaviour connects imagery, affect and action with the central executive system we call Consciousness. The General Theory is founded on the assumption that the primary motivation of all of Consciousness and intentional behaviour is Psychological Homeostasis. Psychological homeostasis is as important to the organisation of mind and behaviour as Physiological Homeostasis is to the organisation of bodily systems. Consciousness processes quasi-perceptual images independently of the input to the retina and sensorium. Consciousness is the “I-Am” control centre for integration and regulation of (my) thoughts, (my) feelings and (my) actions with (my) conscious mental imagery as foundation stones. Imagery vividness, a combination of clarity and liveliness, is essential to imagining, remembering, thinking, predicting, planning and acting. Assessment of vividness using introspective report is validated by objective means such as fMRI. A significant body of work shows that vividness of visual imagery is determined by the similarity of neural responses in imagery to those occurring in perception of actual objects and performance of activities. I am Conscious, therefore I am.

The City of Pasadena is located in southern California; a region which has a Mediterranean climate and where the vast majority of rainfall occurs between October and April with the period between January and March being the most intense. A significant amount of the local water supply comes from regional rainfall, therefore any changes in precipitation patterns in the area has considerable significance. HYPOTHESIS: Local climate change has been occurring in the Pasadena area over the last 100 years resulting in changes in air temperature and rainfall. AIR TEMPERATURES: Between 1886 and 2016 the air temperature in Pasadena, California has increased significantly, from a minimum of 23.8°C in the daytime and 8.1°C at night between 1911 and 1920 to 27.2°C and 13.3°C between 2011 and 2016. The increase in nighttime temperature was uniform throughout the year, however daytime temperatures showed more seasonal variation. There was little change in the daytime temperatures May through July but more change the rest of the year. For example, the median daytime temperature for June between 1911 and 1920 was 27.9°C but was 28.7°C between 2011 and 2016, a difference of 0.8°C. In contrast, for October for the same periods the median daytime temperatures were 25.6°C and 28.9°C, a difference of 3.3°C. RAINFALL: There has been a change in local rainfall pattern over the same period. In comparing rainfall between 1883 – 1949 and 1950 – 2016, there appeared to be less rainfall in the months of October, December, and April while other months seemed to show no change in rainfall. For example, between the two periods mentioned above, the median rainfall in October was 12.4 mm and 8.9 mm respectively while for December they were 68.6 mm and 40.4 mm. There was comparatively a smaller change in the median volume of rainfall in April (18.8 mm vs. 17.5 mm). However, between 1883 and 2016 there were 13 with less than 1 mm of rain, 12 of which occurred after 1961. In the same line of logic, no measureable amount of rain occurred for 23 Octobers, 15 of those occurred after 1961. CONCLUSION: As air temperatures increased over the last 100 years in the Pasadena area, rainfall may have decreased in October, December, and April.

Logical information theory is the quantitative version of the logic of partitions just as logical probability theory is the quantitative version of the dual Boolean logic of subsets. The resulting notion of information is about distinctions, differences, and distinguishability, and is formalized using the distinctions (`dits') of a partition (a pair of points distinguished by the partition). All the definitions of simple, joint, conditional, and mutual entropy of Shannon information theory are derived by a uniform transformation from the corresponding definitions at the logical level. The purpose of this paper is to give the direct generalization to quantum logical information theory that similarly focuses on the pairs of eigenstates distinguished by an observable, i.e., qudits of an observable. The fundamental theorem for quantum logical entropy and measurement establishes a direct quantitative connection between the increase in quantum logical entropy due to a projective measurement and the eigenstates (cohered together in the pure superposition state being measured) that are distinguished by the measurement (decohered in the post-measurement mixed state). Both the classical and quantum versions of logical entropy have simple interpretations as "two-draw" probabilities for distinctions. The conclusion is that quantum logical entropy is the simple and natural notion of information for quantum information theory focusing on the distinguishing of quantum states.

Today, the most powerful approach to detect distant homologs of a protein is based on structure prediction and comparison. Yet this approach is still inapplicable to many viral proteins. Therefore, we developed a powerful sequence-based procedure to identify distant homologs of viral proteins. It relies on 3 main principles: 1) Traces of sequence similarity with a protein can persist beyond the significance cutoff of homology detection programs; 2) Candidate homologs can be identified among proteins with weak sequence similarity to the query, by using "contextual" information, e.g. taxonomy or type of host infected; 3) These candidate homologs can be validated using highly sensitive profile-profile comparison.As a test case, we applied our approach to a protein without known homologs, ORF4 of Lake Sinai virus (which infects bees). We discovered that ORF4 is composed of a domain that has homologs in proteins from >20 taxa of viruses infecting arthropods. We called it “Widespread, Intriguing, Versatile” (WIV) domain because it is found in proteins with a wide variety of domain organizations and functions. For example, WIV is encoded by the NSs protein of tospoviruses, a global threat to food security, which infect plants through arthropod vectors; by the protein encoded by RNA2 ORF1 of chronic bee paralysis virus, a widespread virus of bees; and by various proteins of cypoviruses, which infect the silkworm bombyx mori. WIV has a previously unknown structural fold, according to Alphafold predictions. In some viral species, WIV facilitates infection of arthropods, according to bibliographical evidence

Alopecurus myosuroides (blackgrass) is a problematic weed of Western European winter wheat and its success is largely due to widespread multiple-herbicide resistance. Previous analysis of F2 seed families derived from two distinct blackgrass populations exhibiting equivalent non-target site resistance (NTSR) phenotypes shows resistance is polygenic and evolves from standing genetic variation. Using a CIDER-seq pipeline we show that herbicide resistant (HR) and herbicide sensitive (HS) F3 plants from these F2 seed families as well as the parent populations they were derived from carry extra-chromosomal circular DNA (eccDNA). We identify the similarities and differences in the coding structures within and between resistant and sensitive populations. Although the numbers and size of detected eccDNAs varied between the populations, comparisons between HR and HS blackgrass populations identified shared and unique coding content, predicted genes, and functional protein domains. These include genes related to herbicide detoxification such as Cytochrome P450s, ATP-binding cassette transporters and glutathione transferases including AmGSTF1. eccDNA content was mapped to the Alopecurus myosuroides reference genome, revealing genomic regions at distal end of chromosome 5 and the near center of chromosome 1 and 7 as regions with high number of mapped eccDNA gene density. Mapping to 15 known herbicide-resistant QTL regions showed the eccDNA coding sequences match 12 with four QLT matching HS coding sequences one region only contained HR coding sequences. These findings establish that like other pernicious weeds, blackgrass has eccDNAs that contain homologs of chromosomal genes, and these may contribute genetic heterogeneity and evolutionary innovation to rapidly adapt to abiotic stresses including herbicide treatment.

Abstract: Oncogenic RAS mutations drive more than half of human cancers, and RAS inhibition is the holy grail of oncology. Thirty years of relentless efforts and harsh disappointments have taught us about the intricacies of oncogenic RAS signalling that allow us to now get a pharmacological grip on this elusive protein. The inhibition of effector pathways, such as the RAF-MEK-ERK pathway, has largely proven disappointing. So far, most of these efforts were aimed at blocking the activation of ERK. Here, we discuss RAF dependent pathways that are regulated through RAF functions independent of catalytic activity and their potential role as targets to block oncogenic RAS signalling. We focus on the now well documented roles of RAF kinase independent functions in apoptosis, cell cycle progression and cell migration.

Quasi-solid composited electrolytes were produced by LiFSI initiated polymerized poly-(Dioxolane) (PDOL) with garnet-LLZO (Li7La2Zr3O12) nanofibers and used in lithium-metal batteries. Linear sweep voltammetry shows that the initial oxidation voltage of 4.6 V for Gel-10% (G10, 10% wt. LLZO in PDOL) vs Li/Li+. EIS test of stainless steel// stainless steel symmetric cells for Gel-1% (G1), Gel-5% (G5) and Gel-10% (G10) show ion conductivity (5*10-5 S/cm). Li/G10/Li symmetric cells have stable stripping-plating cycling performance over 1300 hours continuously with the current density of 0.1 mA/cm2 at 25 oC, indicating a good interface contact and stable lithium-ion transport pathway through the composite electrolytes. LFP/G10/Li batteries have stable charge-discharge plateau, low polarization voltage of 0.07-volt, energy efficiency of 95% and coulombic efficiency of ~99% at current density of 26.3 mA/g at 25 oC for over 100 cycles.

The ejido system in Mexico based on communal land was transformed for private ownership due to neoliberal trends during 1990. This research describes the evolution of Mexican land policies that changed the ejido system into private development to answer why land tenure change is shaping urban growth. To demonstrate this, municipalities of San Andrés Cholula and Ocoyucan were selected as a case study. Within this context, we evaluated how much ejido land is being urbanized due to real estate market forces and what type of urbanization model is created. These two areas represent different development scales: S.A. Cholula where its ejidos were expropriated as part of a regional urban development plan; and Ocoyucan where its ejidos and rural land were reached by private developers without local planning. To analyze both municipalities, historical satellite images from Google Earth were used with GRASS GIS 7.4 and corrected with QGIS 2.18. We found that privatization of ejidos fragmented and segregated the rural world for the construction of massive gated-communities. Therefore, a disturbing land tenure change occurred during the last 30 years, hence this research questions the role of local authorities in permitting land use change without regulations or local planning. The resulting urbanization model is a private sector development that isolates rural communities in their own territories, for which we provide recommendations.

With the goal of representing common denominators of aging in different organisms López-Otín et al. in 2013 described nine hallmarks of aging. Since then, this representation has become a major reference point for the biogerontology field. The template for the hallmarks of aging account originated from landmark papers by Hanahan and Weinberg (2000, 2011) defining first six and later ten hallmarks of cancer. Here we assess the strengths and weaknesses of the hallmarks of aging account. As a checklist of diverse major foci of current aging research, it has provided a useful shared overview for biogerontology during a time of transition in the field. It also seems useful in applied biogerontology, to identify interventions (e.g. drugs) that impact multiple symptomatic features of aging. However, while the hallmarks of cancer provide a paradigmatic account of the causes of cancer with profound explanatory power, the hallmarks of aging do not. A worry is that as a non-paradigm the hallmarks of aging have obscured the urgent need to define a genuine paradigm, one that can provide a useful basis for understanding the mechanistic causes of the diverse aging pathologies. We argue that biogerontology must look and move beyond the hallmarks to understand the process of aging.

Dispersal represents a key life-history trait with several implications for the fitness of organisms, population dynamics and resilience, local adaptation, meta-population dynamics, range shifting and biological invasions. Plastic and evolutionary changes of dispersal traits have been intensively studied over the past decades in entomology, in particular in wing-dimorphic insects for which literature reviews are available. Importantly, dispersal polymorphism also exists in wing-monomorphic and wingless insects, and except for butterflies, fewer syntheses are available. In this perspective, by integrating the very last research in the fast moving field of insect dispersal ecology, this review article provides an overview of our current knowledge of dispersal polymorphism in insects. After having provided a definition of the main terms characterising insects’ movements, some of the most often used experimental methodologies for the separation of dispersers and residents in wing-monomorphic and wingless insects are presented. The existing knowledge on the morphological and life-history trait differences between resident and disperser phenotypes is then synthetized. The fourth part examines the effects of range expansion on dispersal traits and performance, in particular for insects from range edges and invasion fronts. Finally, some research perspectives are proposed in the last part of the review.

Over 55% of stoma patients suffer complications such as dehydration. Outcomes may be improved through communicating stoma output data to the patient and their clinical teams. Past artificial neural networks to improve accuracy in fluid level sensing were designed to account for ‘slosh’ caused by variable acceleration in one or two axes of movement. This paper describes the development of a novel sensor platform for non-invasive monitoring of stoma output in real time through incorporating a volumetric array consisting of thermistors and capacitive sensors into an ostomy appliance. Stoma output which exits the body at core temperature passes into a stoma appliance in a pattern which is dictated by water content, existing effluent within the bag and distortion of the usual bag shape. By using thermistors, a thermal boundary demarcates the accumulated level of fecal material as the effluent settles. A capacitive array allows the measurement of volume of output. The sensing components communicates via near field communication (NFC) and transmits data to a smartphone application by Bluetooth low energy (BLE). Testing of the device on 11 existing ileostomy patients with 51.6 bag hours of data found a correlation between measured volume and predictive value, supporting its use in this population.

The Sustainable Development Goals, while complex at first sight, express a simple narrative about the relationships between people and nature. This paper illustrates this in the context of a coral reef land or seascape supporting coastal people. Coral reefs, their health described by measures of coral and fish diversity and abundance, provide key services and benefits to people. These services directly support 10s of millions of jobs in multiple economic sectors in coastal and distant states, protect and harbor communities and cities across tropical coastlines, sustain use of living and non-living resources, provide transport infrastructure and valuable natural products, and in future may provide energy solutions. Through these multiple benefits, coral reefs contribute to reducing hunger and poverty, thus improving health, and potentially strengthening gender and social equality. However, access and use result in pressures that may drive decline in coral reef health. Broader land and seascape factors also affect reef health and therefore delivery of benefits, including land-use change and altered freshwater flows, as well as climate change. Managing this complex system requires appropriate awareness and knowledge, governance mechanisms and investments by stakeholders. This ‘SDG narrative’ can be used from local to global levels, motivating actions and policy at and across these scales to sustain ecosystem function and use, for the oceans what is also increasingly called a blue economy.

Soil and Water Assessment Tool (SWAT) was used to simulate five glacierized river basins that are global in coverage and vary in climate. The river basins included the Narayani (Nepal), Vakhsh (Central Asia), Rhone (Switzerland), Mendoza (Central Andes, Argentina), and Central Dry Andes (Chile) with a total area of 85,000 km2. A modified SWAT snow algorithm was applied in order to consider spatial variation of associated snow melt /accumulation by elevation band across each subbasin. In the previous studies, melt rates varied as a function of elevation resulting from an air temperature gradient while the snow parameters were constant throughout the entire basin. A major improvement of the new snow algorithm is separating the glaciers from seasonal snow based on their characteristics. Two SWAT snow algorithms were evaluated in simulation of monthly runoff from glaciered watershed: 1) the snow parameters are lumped (i.e. constant throughout the entire basin) and 2) the snow parameters are spatially variable based on elevation band-subbasin (i.e. modified snow algorithm). Applying the distributed SWAT snow algorithm improved the model performance in simulation of monthly runoff with snow-glacial regime, so that mean RSR decreased to 0.49 from 0.55 and NSE increased to 0.75 from 0.69. Improvement of model performance was negligible in simulation of monthly runoff from the basins with monsoon runoff regime.

This research investigates the application of Fused Filament Fabrication (FFF) in producing WC-10Co hardmetals, focusing binder formulations and understanding its influence on extrusion force and the influence of printing variables on green density of the samples. By examining the interplay between different binder compositions and backbone contents, the study aims to enhance the mechanical properties of the sintered parts while reducing defects inherent in the printing process. Evidence suggested that formulated feedstocks influenced the hardness of the sintered hardmetal, not due to microstructural changes but to macrostructural responses like macro defects introduced during printing, debinding and sintering of the samples. The results demonstrate the critical role of PP-MA content in improving part density and sintered hardness, suggesting the need for specific thermal debinding protocols tailored to each feedstock. The study provides insights into the formulation of feedstocks for hardmetal FFF, proposing a path toward refining manufacturing processes for better quality and performance of 3D printed hardmetal components.

Chronic degeneration of the Retinal Pigment Epithelium (RPE) is a precursor to pathological changes in the outer retina. The RPE monolayer, which lies beneath the neuroretina, daily internalises and digests large volumes of spent photoreceptor outer segments. Impaired cargo handling and processing in the endocytic/phagosome and autophagy pathways leads to the accumulation of lipofuscin and N-retinylidene-N-retinylethanolamine aggregates and chemically-modified compounds such as malondialdehyde and 4-hydroxynonenal within RPE. These contribute to increased proteolytic and oxidative stress, resulting in irreversible damage to post-mitotic RPE cells and development of blinding conditions such as Age-related Macular Degeneration, Stargardt disease and Choroideremia. Here, we review how impaired cargo handling in the RPE results in their dysfunction, discuss new findings from our laboratory and consider how newly discovered roles for lysosomes and the autophagy pathway could provide insights into retinopathies. Studies of these dynamic, molecular events have also been spurred on by recent advances in optics and imaging technology. Mechanisms underpinning lysosomal impairment in other degenerative conditions including storage disorders, a-synuclein pathologies and Alzheimer’s disease are also discussed. Collectively, these findings help transcend conventional understanding of these intracellular compartments as simple waste disposal bags to bring about a paradigm shift in the way lysosomes are perceived.

Load transfer through orthopaedic joint implants is poorly understood. The longer-term outcomes of these implants are just starting to be studied, making it imperative to monitor contact loads across the entire joint implant interface to elucidate the force transmission and distribution mechanisms exhibited by these implants in service. This study proposes and demonstrates the design, implementation, and characterization of a 3D-printed smart polymer sensor array using conductive polyaniline (PANI) structures embedded within a polymeric parent phase. The piezoresistive characteristics of PANI were studied to characterize the sensing behaviours inherent to these embedded pressure sensor arrays. PANI's stable response to a continuous load, its stability throughout loading and unloading cycles, and its repeatable and linear response to incremental loading cycles together with the accuracy of these measurements were investigated. It is demonstrated that this specially developed multi-material additive manufacturing process for polyaniline is an attractive approach for the fabrication of implant components having embedded smart-polymer sensors for the measurement and analysis of joint loads in orthopaedic implants.

Extensive genome structure variation, such as copy number variations (CNVs) and presence/absence variations, is the basis for the remarkable maize genetic diversity; however, the effect of CNVs on maize herbivory defense remains largely underexplored. Here, we report that the naturally occurring duplication of the maize 9-lipoxygenase gene, ZmLOX5, leads to increased resistance of maize to herbivory by fall armyworms (FAW). Previously, we showed that ZmLOX5-derived oxylipins are required for defense against chewing insect herbivores and identified several inbred lines, including Yu796, that contained duplicated CNVs of ZmLOX5, referred to as Yu796-2×LOX5. To test whether introgression of the Yu796-2×LOX5 locus into the herbivore-susceptible B73 background that contains a single ZmLOX5 gene is a feasible approach to increase resistance, we generated a series of near-isogenic lines that contained either 2, 1 or 0 copies of the Yu796-2×LOX5 locus in the B73 background by six back crosses (BC6). Droplet digital PCR (ddPCR) confirmed the successful introgression of the Yu796-2×LOX5 locus in B73. The resulting B73-2×LOX5 inbred line displayed increased resistance against FAW associated with increased expression of ZmLOX5, increased wound-induced production of its primary oxylipin product, the α-ketol, 9-hydroxy-10-oxo-12(Z),15(Z)-octadecadienoic acid (9,10-KODA), and the downstream defense hormones regulated by this molecule, 12-oxo-phytodienoic acid (12-OPDA) and abscisic acid (ABA). Surprisingly, wound-induced JA-Ile production was not increased in B73-2×LOX5, resulting from the increased JA catabolism. Furthermore, B73-2×LOX5 displayed enhanced drought tolerance likely due to increased ABA and 12-OPDA content. Taken together, this study revealed that the duplicated CNV of ZmLOX5 quantitively contributes to maize antiherbivore defense and presents proof-of-concept evidence that the introgression of naturally occurring duplicated CNVs of a defensive gene into the productive, but susceptible, crop varieties is a feasible breeding approach for enhancing plant resistance to herbivory and tolerance to abiotic stress.

Over the past decade and a half, dynamic functional imaging has revolutionized the neuroimaging field. Since 2009, it has revealed low dimensional brain connectivity measures, has identified potential common human spatial connectivity states, has tracked the transition patterns of these states, and has demonstrated meaningful alterations in these transition and spatial patterns in neurological disorders, psychiatric disorders, and over the course of development. Recently, researchers have begun to analyze this data from the perspective of dynamic system and information theory in the hopes of understanding how these dynamics support less easily quantified processes, such as information processing, cortical hierarchy, and consciousness. Consciousness, in particular, appears to be strongly linked to entropy production in the brain. Little attention has been paid to the effects of psychiatric disease on entropy production in the human brain, however. Even disorders characterized by substantial changes in conscious experience have not been widely analyzed from this perspective. We begin to rectify this by examining the complexity of subject trajectories in state space through the lens of information theory. Specifically, we identify a basis for the dynamic functional connectivity state space and track subject trajectories through this space over the course of the scan. The dynamic complexity of these trajectories is assessed along each dimension of the proposed basis space. Using these estimates, we demonstrate that schizophrenia patients display substantially simpler trajectories than demographically matched healthy controls, and that this drop in complexity concentrates along specific dimensions. We also demonstrate that entropy generation in at least one of these dimensions is linked to cognitive performance. Overall, results suggest great value in applying dynamic systems theory to problems of neuroimaging and reveal a substantial drop in the complexity of schizophrenia patients’ brain function.

Temporomandibular joint disorders (TMD) are characterized by their multifactorial etiology and pathogenesis. A 3-year prospective study was conducted in a Portuguese TMD department to study the prevalence of different TMD signs and symptoms and their association with risk factors and comorbidities. Five hundred ninety-five patients were included using an online database: EUROTMJ. Most patients were female (80.50 %), with a mean age of 38.20±15.73 years. The main complaints were temporomandibular joint (TMJ) clicking (13.26%), pain (12.49%), and masticatory muscle tension (12.15%). The main clinical findings were myalgia (74%), TMJ clicking (60-62%) and arthralgia (31-36%). Risk factors such as clenching (60%) and bruxism (30%) were positively associated with TMJ pain and myalgia. Orthodontic treatment (20%) and wisdom tooth removal (19%) were positively associated with TMJ clicking, while jaw trauma (6%) tracheal intubation (4%) and orthognathic surgery (1%) were positively associated with TMJ crepitus, limited man-dibular range of motion and TMJ pain, respectively. 42.88% of TMD patients had other associated chronic diseases, most of them were mental behavioral or neurodevelopmental disorders (33.76%), namely, anxiety (20%) and depression (13%). The authors also observed a positively association of mental disorders with the degree of TMJ pain and myalgia. Online database seems to be a relevant scientific instrument for healthcare providers who treat TMD. The authors expect that EUROTMJ database can serve as a milestone for other TMD departments.

This article explores the application of machine learning techniques, specifically focusing on ensemble methods like Random Forests, for detecting fraudulent activities in digital financial transactions. Highlighting the evolution from traditional statistical approaches to modern machine learning models, it underscores the effectiveness of Random Forests in handling the inherent challenges of imbalanced datasets typical in fraud detection scenarios. Using a Kaggle dataset of credit card transactions, the study optimizes Random Forest parameters through rigorous parameter tuning, achieving significant improvements in model performance metrics such as Area Under the Curve (AUC). The findings underscore the critical role of machine learning in enhancing fraud detection capabilities, emphasizing the ongoing evolution and future potential of these methodologies in financial risk management.

Surgical simulators are crucial in early craniofacial and plastic surgical training, necessitating synthetic materials that accurately replicate tissue properties. Recent critiques of our lab’s currently deployed silicone surrogate have highlighted numerous areas for improvement. To further refine our models, our group's objective is to find a composition of materials that is closest in fidelity to native oral mucosa during surgical rehearsal by expert craniofacial surgeons. Fifteen platinum silicone-based surrogate samples were constructed with variable hardness and slacker percentages. These samples underwent evaluation of tactile sensation, hardness, needle puncture, cut resistance, suture retention, defect repair, and tensile elasticity. Expert craniofacial surgeon evaluators provided focused qualitative feedback on selected top-performing samples for further assessment and statistical comparisons. Evaluation revealed surrogate characteristics with satisfactory to good performance. Sample 977 exhibited the highest performance, and comparison with the original surrogate (sample 810) demonstrated significant improvements in critical areas, emphasizing the efficacy of the refined composition. The study identified a silicone composition that directly addresses the feedback received by our team’s original silicone surrogate. The study underscores the delicate balance between biofidelity and practicality in surgical simulation. The need for ongoing refinement in surrogate materials is evident to optimize training experiences for early surgical learners.

Background: This study assessed the nature of healthcare services offered in the David Umahi Federal University of Health Sciences health clinic and students' disposition to access the facility. Objectives: To assess the knowledge, attitude and practice of students in accessing healthcare services in the David Umahi Federal University of Health Sciences health clinic.Methods: Used cross-sectional design, a structured questionnaire of a five-point Likert scale as a veritable instrument for collecting the data from 50 student respondents. The questionnaire is made up of four key sections comprising student’s demographic parameters, knowledge, attitude and practice of both students and the clinic staff. Data collected was analyzed in a table of descriptive statistics to determine the total, range, mean and median, which were used to ascertain students’ utilization/accessibility disposition, perception of barriers to accessing healthcare service and overall viability of the clinic.Results: The mean value outcome of knowledge of students falls between 3.1 and 3.9, the mean value for attitude of students falls between 2.5 to 3.4 and 4.0, while the practice of students falls between mean values 2.6 and 3.1. Most of these outcomes represent poor or weak weight factor which requires several levels of intervention.Conclusion: This study highlights the overriding importance of the university healthcare clinic in maintaining a healthy study season among students of David Umahi Federal University of Health Sciences and their health-seeking behaviour. This helps to promote health, attract higher intakes and retain them in the institution till graduation.

This paper examines the potential of Artificial Intelligence (AI) to address societal megatrends, with a specific focus on OpenAI’s Generative Pre-Trained Transformer 3 (GPT-3). To do this, we con-ducted an analysis using GPT-3 in order to explore the benefits of AI for digitalization, urbanization, globalization, climate change, automation and mobility, global health issues and aging population. We also looked at emerging markets as well as sustainability in this study. Interaction with GPT-3 was done solely through prompt questions and generated responses were analyzed. Our results indicate that AI can significantly improve our understanding of these trends by providing insights into how they develop over time and what solutions could be implemented. Further research is needed to determine how effective AI will be in addressing them successfully but initial findings are encouraging. Our discussion focuses on the implications of our findings for society going forward and suggests that further investigation should be done into how best to utilize new technologies like GPT-3 when tackling these challenges. Lastly, we conclude that while there is still much work left to do before any tangible effects can be seen from utilizing AI tools such as GPT-3 on societal mega-trends; early indications suggest it may have a positive impact if used correctly.

Background In this study we investigated in detail the role of cannabidiol (CBD), Beta-caryophyllene (BC), or their combinations in diabetic peripheral neuropathy (DN). The key factors that contribute to DN include mitochondrial dysfunction, inflammation, and oxidative stress. Methods Briefly, Streptozotocin (STZ) (55 mg/kg) was injected intraperitoneally to induce DN in Sprague Dawley rats and performed procedures including Randall Sellito Calipers, Von Frey Aesthesiometer, hot plate, and cold plate methods to determine mechanical and thermal hyperalgesia in vivo. The blood flow to the nerves was assessed by using the Laser Doppler device. Schwann cells were exposed to high glucose (HG) at a dose of 30 mM to induce hyperglycemia and DCFDA, JC1 & Mitosox staining were done to determine mitochondrial membrane potential, reactive oxygen species and mitochondrial superoxides in-vitro. The rats were administered i.p with BC (30mg/kg), CBD (15mg/kg), or combination while Schwann cells were treated with 3.65 µM CBD, 75 µM BC, or combination to assess their role in DN amelioration. Results Our results revealed that exposure to BC and CBD diminished HG-induced hyperglycemia in Schwann cells, in part, through reducing mitochondrial membrane potential, reactive oxygen species and mitochondrial superoxides. Further, BC and CBD combination treatment in-vivo could prevent the deterioration of mitochondrial quality control system by promoting autophagy and mitochondrial biogenesis while improving blood flow. CBD and BC treatments also reduced pain hypersensitivity to hyperalgesia and allodynia with increased antioxidant and anti-inflammatory action in diabetic rats. These in vivo effects were attributed to significant upregulation of AMPK, SIRT3, Nrf2, PINK1, PARKIN, LC3B, Beclin1 and TFAM functions while downregulation of NLRP3 inflammasome, NFκB, COX2 and p62 activity was noted as determined by western blotting. Conclusion the present studies demonstrated that STZ & HG induced oxidative and nitrosative stress play a crucial role in the pathogenesis of diabetic neuropathy. We find, for the first time, that CBD and BC combination ameliorate DN via modulating the mitochondrial quality control system.

Soil-borne Trichoderma spp. have been extensively studied for their biocontrol activities against pathogens and growth promotion ability with plants. However, the beneficial effect of Trichoderma on inducing resistance against insect herbivores has been considered only recently. Among diverse Trichoderma species, consistent with previous reports, we showed that root colonization by T. virens triggered induced systemic resistance (ISR) to leaf-infecting fungal pathogens. Whether T. virens induces ISR to insect pests has not been tested before. In this study, we investigated whether T. virens affects jasmonic acid (JA) biosynthesis and defense against fall armyworm (FAW) and western corn rootworm (WCR). Unexpectedly, the results showed that T. virens colonization of maize seedlings grown in autoclaved soil suppressed wound-induced production of JA, resulting in reduced resistance to FAW. Similarly, the bacterial endophyte Pseudomonas chlororaphis 30-84 suppressed systemic resistance to FAW due to reduced JA. Further comparative analyses of the systemic effects of these endophytes when applied into sterile or non-sterile field soil showed that both T. virens and P. chlororaphis 30-84 triggered ISR against hemibiotrophic fungal pathogen Colletotrichum graminicola in both soil conditions, but only suppressed resistance to FAW in sterile soil. In contrast to the effect on FAW defense, T. virens colonization of maize roots suppressed WCR larvae survival and weight gain. This is the first report suggesting the potential role of T. virens as a biocontrol agent against WCR.

Whether the universe is a computer simulation, or whether we wish to efficiently model our universe in a computer simulation, there would be benefits to modeling it in a fashion analogous to computer spreadsheet, each lattice cell can be conceived as containing all the mathematical formula necessary to continuously compute its state relative to changes in all its neighboring cells, and by progression, in relation to all the cells of entire space-time lattice. Alternatively, the “real” universe may itself be built on a space cell lattice, an irregular foam of space cells, in which each cell may be conceived as a multidimensional cell of distortable space, the shape of which fully describes (a) the four basic forces (gravity, electromagnetic, strong, weak) observed at that cell of space, and (b) the probability (or weight distribution) of any quantum states overlapping the cell and its neighbors. At an appropriate scale, it would appear that this conceptual model would resolve apparent conflicts between general relativity and quantum physics. It would also provide a new interpretation of Planck’s constant as description of the number of space cell events associated with any set of observable events. If formulae operating at a lattice cell level can be improve our ability to understand and model larger scale phenomena, this would be strong evidence in favor of the theory that mathematics is not just a human invention but rather an inherent feature of space-time itself.