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

Nicotinamide mononucleotide (NMN), a key NAD+ precursor, exhibits distinct metabolic characteristics and potential health benefits. Recent investigations underscore the pivotal role of gut bacteria and specialized uptake mechanisms in NMN metabolism. While human trials demonstrate NMN's safety and promising health outcomes, challenges persist. Variability in results is likely influenced by lifestyle, health conditions, and individual genetic and gut microbiota differences. Understanding how these factors affect NMN metabolism is crucial for personalized approaches and maximizing NMN's potential. Advances in delivery systems show promise for enhancing NMN bioavailability, but further understanding of optimal NAD+ levels and reliable measures of NMN's effects is necessary. This comprehensive approach is key to optimizing NMN's impact on human health and longevity.

The hybrid bond graph has been studied in depth for scalar bond graphs, but how does this translate to the multi-bond graph? Here, the controlled junction – used to model structural switching such as contact – is extended to the multi-bond case. This is a simple process, assuming that all bonds switch simultaneously (which makes physical sense). A controlled 0-junction is applied to multi-bond graph of a car, which can lose contact with the ground in cornering. Dynamic causality features, but this can be accommodated using an equational submodel in 20-Sim (in a manner similar to that used with scalar bond graphs). The junction is proposed for subsequent work to develop a validated multi-body dynamics car model in cornering.

Background: Educating college students about the importance of good sleep habits could lead to the adoption of healthier sleep routines, including sufficient sleep duration and sleep quality. The current pre-post study examines the impact of completing a sleep education program called “Sleep 101” on (1) sleep hygiene practices, (2) sleep quality, and (3) weekday and weekend sleep behaviors among college students. “Sleep 101” is an interactive online course developed to educate college students about the importance of sleep by addressing basic sleep physiology, the impact of sleep on mood, academic and physical performance, the interactions between sleep and various substances, and common sleep disorders. Methods: 338 college students were recruited from a midsized public university in the US and invited to participate in “Sleep 101”, of which 25 participants completed the baseline and post-intervention questionnaire. The Sleep Hygiene Index (SHI) was utilized to evaluate sleep hygiene practices, while standard questions were employed to assess weekday and weekend sleep behaviors and overall sleep quality. Results: Those who completed the study demonstrated a significant increase in weekday sleep duration and were less likely to engage in negative prior bedtime activities. In addition, 40% of those who completed baseline and post-intervention assessments noticed improvements in their sleep quality. Conclusion: These findings suggest that a brief online program is beneficial in improving sleep behaviors among college and could be a scalable approach to addressing current sleep issues and preventing future sleep problems in college students.

The phylogeny of Neoaves, the largest clade of extant birds, has remained unclear despite intense study. The difficulty associated with resolving the early branches in Neoaves is likely driven by the rapid radiation of this group. However, conflicts among studies may be exacerbated by the hypothesis that relationships are sensitive to the data type analyzed. For example, analyses of coding exons typically yield trees that place Strisores (nightjars and allies) sister to the remaining Neoaves, while analyses of non-coding data typically yield trees where Mirandornites (flamingos and grebes) is the sister of the remaining Neoaves. Our understanding of data type effects is hampered by the fact that previous analyses have used different taxa, loci, and types of non-coding data. Herein, we provide strong corroboration of the data type effects hypothesis for Neoaves by comparing trees based on coding and non-coding data derived from the same taxa and gene regions. A simple analytical method known to minimize biases due to base composition (coding nucleotides as purines and pyrimidines) resulted in coding exon data with increased congruence to the non-coding topology using concatenated analyses. These results improve our understanding of the resolution of neoavian phylogeny and point to a challenge - data type effects - that is likely to be an important factor in phylogenetic analyses of birds (and many other taxonomic groups). Using our results, we provide a summary phylogeny that identifies well-corroborated relationships and highlights specific nodes where future efforts should focus.

The campuses of Nigerian universities especially the old ones, like the University of Ibadan, comprise old trees which can pose a threat to pedestrians, structures, and roads within the school environments. However, there is no adequate information on these avenue trees thereby impeding their sustainable management. Therefore, this study provides the basic information needed by developing a geodatabase for the avenue trees along Benue, Emotan and Oduduwa roads within the University of Ibadan, Ibadan, Nigeria. The coordinates of all the avenue trees, and some within the selected roads were obtained. Tree growth data collected include; diameter at the breast height (dbh), diameter at the base, middle and at the top, crown height, crown diameter, and total height of all the avenue trees. Tree visual evaluation for diseases (TVED) was carried out for root decay, and termite attack on any part of the tree (stem, leaves and visible part of the root). Risk rate was assessed as low, medium and high, depending on the potential target (human, vehicles, structures). The risk rate depended on the incidence of leaning towards a building or road, cracked branches, root attack by termites, basal decay or branch decay. The growth data were used to compute the tree volume while the avenue trees were georeferenced. The physical health status of the avenue trees was determined using TVED data. The spatial distribution of the avenue trees was developed in GIS while all the analysed data were pulled together to develop a geodatabase for the avenue tress using design templates of BOOTSTRAP, comprising of Hypertext Markup Language, Cascade Style Sheets, JavaScripts and Hypertext Preprocessor. A total of 121 individual avenue trees belonging to 14 species were identified in the study area. The analysis of the geospatial distribution shows that Emotan Road had a lesser spatial distribution of avenue trees compared to Benue and Oduduwa roads. Furthermore, the health risk assessment of the trees in the study area indicated that 17.35% of the individual avenue trees had defects. The database created is user-friendly, suitable and has the ability for easy data storage and quick information retrieval on the avenue trees to enhance their maintenance and risk management. This can be accessed using the link http://159.203.29.155/rebs/rebs.php.

The links between mindfulness, savoring positive experiences, and depressive symptoms have been well-established in the literature. Nevertheless, little has been done to disentangle the prospective relations among these constructs. Clarifying the longitudinal relations is crucial, as it enables researchers and practitioners to discern potential trajectories of mental health interventions. In this study, 180 emerging adults between 18 and 27 years old were recruited twice at 3 months apart to complete self-reported measures including mindfulness, savoring positive experiences, and depressive symptoms. Cross-lagged path analysis indicated that savoring the moment was predictive of mindfulness three months later, whereas depressive symptoms were predictive of both mindfulness and savoring the moment three months later, above and beyond the effects of age, gender, and family income. Additionally, mindfulness, savoring positive experiences, and depressive symptoms were significantly correlated at baseline. The present study evidenced short-term inversed effects of depressive symptoms on mindfulness and savoring the moment, as well as a positive effect of savoring the moment on mindfulness. Hence, interventions gearing towards symptom reduction of depression are likely to carry concurrent and prospective benefits of psychological functioning, namely the ability to be present in the moment and to savor. Taken together, reducing depressive symptoms may be crucial in fostering psychological well-being.

Although the presence of dark energy is well established from various observations, its true nature is still not well understood. The cosmological constant term seems to be the preferred candidate. In earlier work we had a constant cosmological constant term to limit the sizes of large-scale structures at lower redshifts. In this work, we extend this to large scale structures at higher redshifts. Here we invoke a time varying cosmological constant to set constraints on sizes of galaxies at high redshifts and see that they are consistent with their observed sizes. The time-varying cosmological constant also provides a possible solution to the puzzle of structure formation of large disk galaxies (like the Wolfe disk) observed at very early stages of the Universe. Future observations of galaxies at even higher redshifts could support our approach.

Complex modeling has received significant attention in recent years and is increasingly used to explain the statistical phenomenon with increasing and decreasing fluctuations such as the similarity or difference of spike protein charge patterns of coronaviruses. Different from the existing covariance or correlation coefficient methods in traditional integer dimension construction, this study proposes a simplified novel fractional dimension derivation with the exact Excel tool algorithm. It involves the fractional center moment extension to covariance, which ends up a complex covariance coefficient that is better than the Pearson correlation coefficient, in the sense that the nonlinearity relationship can be further depicted. The spike protein sequences of coronaviruses were obtained from the GenBank and GISAID database, including the coronaviruses from pangolin, bat, canine, swine (three variants), feline, tiger, SARS-CoV-1, MERS, and SARS-CoV-2 (including the strains of Wuhan, Beijing, New York, German, and UK variant B.1.1.7) were used as the representative examples in this study. By examining the values above and below the average/mean based on the positive and negative charge patterns of the amino acid residues of the spike proteins from coronaviruses, the proposed algorithm provides deep insights into the nonlinear evolving trends of spike proteins for understanding the viral evolution and identifying the protein characteristics associated with viral fatality. The calculation results demonstrate that the complex covariance coefficient analyzed by this algorithm is capable of distinguishing the subtle nonlinear differences in the spike protein charge patterns with reference to Wuhan strain SARS-CoV-2 for which the Pearson correlation coefficient may overlook. Our analysis reveals the unique convergent (positive correlative) to divergent (negative correlative) domain center positions of each virus. The convergent or conserved region may be critical to the viral stability or viability; while the divergent region is highly variable between coronaviruses suggesting high frequency of mutations in this region. The analyses show that the conserved center region of SARS-CoV-1 spike protein is located at amino acid residues 900, but shifted to the amino acid residues 700 in MERS spike protein, and then to amino acid residues 600 in SARS-COV-2 spike protein, indicating the evolvement of the coronaviruses. Interestingly, the conserved center region of the spike protein in SARS-COV-2 variant B.1.1.7 shifted back to amino acid residues 700, suggesting this variant is more virulent than the original SARS-COV-2 strain. Another important characteristic our study reveals is that the distance between the divergent mean and the maximal divergent point in each of the viruses (MERS>SARS-CoV-1>SARS-CoV-2) is proportional to viral fatality rate. This algorithm may help to understand and analyze the evolving trends and critical characteristics of SARS-COV-2 variants, other coronaviral proteins and viruses.

The purpose of this qualitative study was to describe parent perceptions of the home exercise pro-gram (HEP) for their infant with congenital muscular torticollis (CMT), and how these perceptions evolved over a physical therapy (PT) plan of care. Twelve participants were recruited from a pediatric PT clinic, and nine completed interviews at three time points. Qualitative description and an iterative approach for thematic analysis of 27 interviews yielded three themes that corresponded to the research questions. The participants’ responses were categorized into three main themes: 1) parents’ perceptions of three key exercises within the HEP; 2) internal and external sources of stress; and 3) sources of empowerment and disempowerment. Regarding the HEP, parents articulated common sentiments for three frequently prescribed exercises for the management of CMT: 1) Tummy time was the fast favorite, 2) ipsilateral cervical rotation was perceived as stressful, and 3) contralateral cervical lateral flexion felt uncomfortable. Additionally, participants disclosed internal and external sources of stress (guilt, uncertainty, and the demands of returning to work) and sources of disempowerment (inconsistent messaging from providers, feeling overwhelmed) and empowerment (being able to see the bigger picture and clear communication and education about the diagnosis) with respect to managing their infant’s CMT. These themes provide insight into the evolution of parent perceptions over a PT plan of care for CMT. Participants’ insights suggest a need for consistent messaging regarding the diagnosis and evidence-based management of CMT, addressing parent stress, and modifying how exercises are taught. This study contributes updated research on parents’ experience with physical therapy and the HEP for their infant’s CMT.

Although relatively rare, affecting 8% of the general population, autoimmune disorders are causative linked with chronic diseases and morbidity. Control of the course of the disease is closely dependent on the ability to monitor its onset as well as response to treatment. In the present report, we review the progress in the development of biosensor-based approaches and related tools for the Point-of-Care diagnosis and monitoring of biomarkers related to several autoimmune diseases, such as Myasthenia Gravis, Rheumatoid Arthritis, Multiple Sclerosis, Systemic Erythematosus Lupus, Crohn’s Disease, Diabetes Mellitus, Behcet’s disease, Psoriasis and Celiac Disease. Various biosensing technologies are discussed, including electrochemical, optical and mechanical ones, along with the use of advanced nanomaterials and immobilization techniques for the biorecognition elements. The need for innovative devices with unique features of rapid, low-cost, real-time detection is considered in the context of preventing permanent organ and tissue damage from chronic autoimmune diseases.

Continual learning (CL), a.k.a lifelong learning, is an emerging research topic that has been attracting increasing interest in the field of machine learning. With human activity recognition (HAR) playing a key role in enabling numerous real-world applications, an essential step towards the long-term deployment of such systems is to extend the activity model to dynamically adapt to changes in people’s everyday behavior. Current research in CL applied to HAR domain is still under-explored with researchers exploring existing methods developed for computer vision in HAR. Moreover, analysis has so far focused on task-incremental or class-incremental learning paradigms where task boundaries are known. This impedes the applicability of such methods for real-world systems. To push this field forward, we build on recent advances in the area of continual learning and design a lifelong adaptive learning framework using Prototypical Networks, LAPNet-HAR, that processes sensor-based data streams in a task-free data-incremental fashion and mitigates catastrophic forgetting using experience replay and continual prototype adaptation. Online learning is further facilitated using contrastive loss to enforce inter-class separation. LAPNet-HAR is evaluated on 5 publicly available activity datasets in terms of its ability to acquire new information while preserving previous knowledge. Our extensive empirical results demonstrate the effectiveness of LAPNet-HAR in task-free CL and uncover useful insights for future challenges.

School closures (SC) were adopted globally as a COVID-19 disease pandemic containment strategy. This extreme measure provoked a disruption of the educational system involving hundreds of million children worldwide. The return of children to school has been variable and is still an unresolved and contentious issue. Importantly the process has not been directly correlated to the severity of the pandemic s impact and has fueled the widening of disparities, disproportionately affecting the most vulnerable populations. Available evidence shows SC added little benefit to COVID-19 control whereas the harms related to SC severely affected children and adolescents. This unresolved issue has put children and young people at high risk of social, economic and health-related harm for years to come, triggering severe consequences during their lifespan. In this article we describe the process of SC and the reopening timetable across the globe. We highlight the data regarding the international state of educational systems around the world, putting emphasis on the rights of children to come back to school.

Background and Objectives: Gastric cancer (GC) is one of the most commonly diagnosed cancer and the fourth cause of cancer death worldwide. Personalised treatment improves GC outcomes. A molecular classification is needed to choose the appropriate therapy. A classification that uses on-slide biomarkers and formalin-fixed and paraffin-embedded (FFPE) tissue is preferable to comprehensive genomic analysis. In 2016, Setia et al. proposed an on-slide classification, however this is not in widespread use. We propose a modification of this classification that has six subgroups: GC associated with Epstein-Barr virus (GC EBV+), GC with mismatch repair deficiency (GC dMMR), GC with epithelial-mesenchymal transformation (GC EMT), GC with functional loss of p53 due to mutation (GC p53m), CG with intact p53 (GC p53wt) and GC not otherwise specified (GC NOS). This classification also has provision for biomarkers for current or emerging targeted therapies (Her2, PD-L1 and Claudin18.2). Here we assess the implementation and feasibility of this inclusive working classification. Materials and Methods: We constructed a tissue microarray library from a cohort of 79 resection cases from FFPE tissue archives. We used a restricted panel of on-slide markers (EBER, MMR, E-cadherin, beta-catenin and p53), defined their interpretation algorithms, and assigned each case to a specific molecular subtype. Results: GC EBV(+) cases were 6%, GC dMMR cases were 20%, GC EMT cases were 14%, GC p53m cases were 23%, GC p53wt cases were 29% and GC NOS cases were 8%. Conclusions: This working classification uses markers that are widely available in Histopathology and are easy to interpret. A diagnostic subgroup is obtained for 92% of the cases. The proportion of cases in each subgroup is in keeping with other published series. Widescale implementation appears feasible. A study using endoscopic biopsies is warranted.

Avian sex chromosomes evolved after the divergence birds and crocodilians from their common ancestor, so they are much younger than the better-studied chromosomes of mammals. It has long been recognized that there may have been several stages to the evolution of avian sex chromosomes. For example, the CHD1 undergoes recombination in paleognaths but not neognaths. Genome assemblies have suggested there may be variation in the timing of barriers to recombination among Neognathae, but there remains little understanding of the extent of this variability. Here, we look at partial sequences of ATP5F1A, which is on the avian Z and W chromosomes. It is known that recombination of this gene has independently ceased in Galliformes, Anseriformes, and at least five neoavian orders, but whether there are other independent cessations of recombination among Neoaves is not understood. We used a combination of data extracted from published chromosomal-level genomes with data collected using PCR and cloning to identify Z and W copies in 22 orders. Our results suggest there may be at least 19 independent cessations of recombination within Neognathae, and 3 clades that may still be undergoing recombination (or have only recently ceased recombination). Analyses of ATP5F1A protein sequences revealed an increased amino acid substitution rate for W chromosome gametologs, suggesting relaxed purifying selection on the W chromosome. Supporting this hypothesis, we found that the increased substitution rate was particularly pronounced for buried residues, which are expected to be more strongly constrained by purifying selection. This highlights the dynamic nature of avian sex chromosomes, and that this level of variation among clades means they should be a good system to understand sex chromosome evolution.

The definitive negative results of various direct searches for dark matter particles and non-observation of them has increasingly indicated that we should consider alternate models like the Modification of Newtonian Dynamics (MOND) and Modification of Newtonian Gravity (MONG). It is puzzling how the Oort cloud, despite its great distance from the Sun, is gravitationally bound to the Sun’s gravity. In this work, we suggest that this could be explained by the modifications to Newtonian dynamics (MOND) and to gravity (MONG).

Building on a framework of risk transmission to children of depressed parents, the present study investigated the associations between parents’ self-compassion, parent’s depressive symptoms, and child adjustment. A total 189 Chinese parents (101 mothers) whose children were 2-8 years old were recruited to complete a questionnaire, including measures of self-compassion, depressive symptoms and children’s prosocial behavior, internalizing problems, and externalizing problems. Findings indicated mediation effects, in that parents’ depressive symptoms mediated the associ-ation between their self-compassion and child adjustment outcomes, namely children’s internal-izing and externalizing problems, after controlling the effects of monthly family income, child gender, and parent gender. Competing hypothesis suggested that parents’ self-compassion did not moderate between parents’ depressive symptoms and child adjustment outcomes. Hence, the association between parental depressive symptoms and child adjustment was not dependent on the level of parents’ self-compassion. As an implication, researchers and practitioners should be made aware of the protective role of parents’ self-compassion in the family context.

Phylogenomic analyses have revolutionized the study of biodiversity, but they have revealed that estimated tree topologies can depend, at least in part, on the subset of the genome that is analyzed. For example, estimates of trees for avian orders differ if protein coding or non-coding data are analyzed. The bird tree is a good study system because the historical signal for relationships among orders is very weak, which should permit subtle non-historical signals to be identified, while monophyly of orders is strongly corroborated, allowing identification of strong non-historical signals. Hydrophobic amino acids in mitochondrially-encoded proteins, which are expected to be found in transmembrane helices, have been hypothesized to be associated with non-historical signals. We tested this hypothesis by comparing the evolution of transmembrane helices and extramembrane segments of mitochondrial proteins from 420 bird species, sampled from most avian orders. We estimated amino acids exchangeabilities for both structural environments and assessed the performance of phylogenetic analysis using each data type. We compared those relative exchangeabilities with values calculated using a substitution dataset for transmembrane helices from a variety of sampled set of nuclear- and mitochondrially-encoded proteins, allowing us to compare the bird-specific mitochondrial models with a general model of transmembrane protein evolution. To complement our amino acid analyses, we examined the impact of protein structure on patterns of nucleotide evolution. Models of transmembrane and extramembrane sequence evolution for amino acids and nucleotides exhibited striking differences, but there was no evidence for strong topological data type effects. However, incorporating protein structure into analyses of mitochondrially-encoded proteins improved model fit. Thus, we believe that considering protein structure will improve analyses of mitogenomic data, both in birds and in other taxa.

The Digital Twin is one of the big technology trends of the last decade. In the course of its rapid expansion into the various fields of application, many different definitions emerged, tailored to the respective applications. Taxonomies can cluster the diversity and define application-specific archetypes. This paper presents a characterization of the Digital Twin in the context of structural mechanics and lightweight design. It begins by exploring various definitions of the Digital Twin concept and its application in different industries. The paper further analyzes the product life cycle of structures, dividing it into the design and operational phases and identifying the requirements for a Digital Twin in each phase. The structural design process is examined, including the definition of a structure and the stages of the product development process. Additionally, the paper discusses the operational phase of structures, highlighting the need for continuous monitoring, evaluation, and adaptation through Structural Health Monitoring (SHM) systems. The paper proposes two archetypes of Digital Twins for structures: a structure-designing Digital Twin for the design phase and a structure-monitoring Digital Twin for the operational phase. The findings provide a framework for implementing Digital Twins in structural mechanics, enabling digital design and monitoring of structures for improved performance and maintenance strategies.

Local anaesthetic agents suppress action potentials in excitable tissues by blocking voltage-gated sodium channels. In doing so they inhibit the depolarisation of nociceptive nerve fibres and so prevent the transmission of pain impulses. UK legislation allows HCPC-registered Podiatrists with POM-A annotation access to six local anaesthetic drugs and two of these with the addition of adrenaline. The use of local anaesthetia has transformed the treatment of nail pathology by Podiatrists. In the UK, the drug of choice in podiatric practice is 3% mepivacaine hydrochloride: it is a good choice of drug for digital anaesthesia. This paper will review the chemistry, pharmacology and dose calculation of mepivacaine, and challenge some of the orthodoxy over the rigid calculation of maximum safe dosages.

Experiences of homelessness, although widely varied, are characterized by extensive time in public spaces, often outdoors. However, there has been little empirical research about the ways in which environmental factors affect individuals experiencing homelessness (IEHs). Therefore, the purpose of this study was to use an environmental justice approach to understand how cardiopulmonary health of IEHs is affected by episodic poor air quality in Salt Lake County. It was hypothesized that people who had experienced unsheltered homelessness and those who had been experiencing homelessness for longer periods of time would report greater health difficulties from poor air quality exposure. Through a combination of in-person semi-structured interviews with IEHs (n = 138) and access to corresponding state-based service provider databases, researchers examined both overall descriptives of and relationships between types (sheltered and unsheltered) and duration (chronic and non-chronic) of homelessness. More than 61% of IEHs reported physical reactions to air pollution, 37% reported air pollution-related emotional stress, and more than 89% had sought medical attention for a condition related to air pollution. Findings indicate that while IEHs report a number of health effects related to poor air quality, there were no significant differences between individuals based on either sheltered status or duration of their experiences of homelessness. This study provides an initial empirical inquiry to understand how environmental disamenities negatively influence IEHs, as well as noting that sheltered status and duration of homelessness are less impactful than originally hypothesized.

The objective of this study is to determine the relationship between body condition score (BCS) and body carcass fat (BCF) of ewes at two key stages of the production cycle. Data were collected from 88 Coopworth ewes including BCS measurements manually evaluated by the farm manager, BCF measurements determined by computerized tomography (CT) and body parameter measurements automatically determined by an image processing application. Artificial neural network (ANN) statistical analysis method was used to develop a relationship between the body parameters and the BCF with an r2=0.96 and RMSE=1.01 using all top and side variables.

The use of improved agricultural technologies has been reported as the major strategy to increase agricultural production, increased household incomes and addressing poverty. However, adoption of such improved technologies by smallholder coffee farmers has been slow and this has contributed to the low coffee productivity in the country and the poor performance of the coffee sub sector. The study was meant to examine the effect of institutional factors including extension services, access to market and access to credit on technology adoption among smallholder coffee farmers in Kanungu District, Uganda. The study collected both quantitative and qualitative data from 289 smallholder coffee farmers and 8 key informants respectively in major coffee growing sub counties in Kanungu district. The study revealed that access to extension services and access to market have a positive significant influence on agricultural technology adoption while access to market has no significant influence on agricultural technology adoption. The study concluded that there is a positive significant relationship between institutional factors and technology adoption among smallholder coffee farmers in Kanungu district.

Haemaphysalis longicornis (Neumann, 1901) (Acari: Ixodidae), the Asian longhorned tick, is an invasive tick species present in the USA since at least 2017 and has been detected in one-third of Virginia counties. While this species is associated with the transmission of multiple pathogens in its native geographical range of eastern Asia, little is known about its ability to acquire and transmit pathogens in the USA, specifically those that are transmissible to humans, although from an animal health perspective it has already been shown to vector Theileria orientalis Ikeda strains. Emerging tick-borne viruses such as Bourbon virus (genus: Thogotovirus) are of concern as these newly discovered pathogenic agents have caused fatal clinical cases, and little is known about their distribution or enzootic maintenance. This study examined H. longicornis collected within Virginia (from ten counties) for Bourbon and Heartland virus using PCR methods. All ticks tested negative for Heartland virus via qRT-PCR. Bourbon virus-positive samples were confirmed on two different gene targets, and with Sanger sequencing of the PB2 (segment 1) gene. Bourbon virus RNA was detected in one nymphal stage H. longicornis from Patrick County, one nymph from Staunton City, one larval pool and one adult female tick from Wythe County, Virginia. An additional 100 Amblyomma americanum (Linnaeus 1758; lone star tick) collected at the same Patrick County site revealed one positive nymphal pool, suggesting that Bourbon virus may have spilled over from the native vector, potentially by co-feeding on a shared Bourbon virus-infected vertebrate host. Blood tested from local harvested deer revealed a 12.0% antibody seroprevalence against Bourbon virus, exposure which further corroborates that this tick-borne virus is circulating in the Southwest Virginia region. Through these results it can be concluded that H. longicornis can carry Bourbon virus and that pathogen spillover may occur from native to invasive tick species.

The estimation of the Hubble constant in the past few decades has increasingly become more accurate with the advance of new techniques. But its value seems to depend on the epoch at which the measurements are made. The Planck estimate of the Hubble constant from the observations of the CMBR in the early Universe is about 67.

The presence of dark matter, though well established by indirect evidence is yet to be observed directly. Various dark matter detection experiments running for several years have yielded no positive results so far. In view of these negative results, we had earlier proposed alternate models by postulating a minimum gravitational field strength (minimum curvature) and also a minimum acceleration. These postulates led to the modified Newtonian dynamics and modified Newtonian gravity (MONG). The observed flat rotation curves of galaxies had also been accounted for through these postulates. Here we extend these postulates to galaxy clusters and model the dynamical velocity-distance curves for such large-scale structures. The velocity-distance curve of the Virgo cluster, plotted with this model is found to be in accordance with that observed.

Here we propose a modification of the gravitational field on large scales as an alternate explanation for the discrepancy in the value of the Hubble constant as implied by Planck observations of the CMBR in the early Universe and that deduced from other distance indicators in the present epoch.

Background and Objectives: Mucilaginous substances from plant extracts are known to be able to support the lubricating effect of hyaluronic acid (HA) in dry eye disease (DED). In this pilot study, the combined lubricating effect of HA and mallow extract (Malva sylvestris L.) in patients with DED was assessed. Materials and Methods: 20 patients at 5 ophthalmological practices in Italy were treated with eye drops, containing HA and mallow extract on the one hand, and with eye drops containing HA only, on the other hand, in a two-period crossover design. As primary endpoints, the tear film breakup time (TBUT), the reduction of lissamine green staining of the ocular surface (Oxford Scheme, OS), and the safety and efficacy assessment by the ophthalmologists were evaluated. As secondary variables, the patient symptom score, the ocular surface index (OSDI), and the satisfaction, preference and efficacy judgement by the patients were evaluated. All data were analysed descriptively in addition to an exploratory analysis of the target variables. Results: Both products were well tolerated. There were no statistically significant differences, with regard to the TBUT, OS and OSDI, between both treatments. Anyway, the efficacy and safety assessments by the ophthalmologists and the patients showed results in favour of the combined product. Conclusion: The addition of mallow extract to HA containing eye drops enhances the treatment of DED at least with respect to subjective measurements. Further assessments will have to be done to prove and explain this observation in terms of measurable parameters, e.g. markers for inflammatory cytokines.

The latest IPCC report forcefully states that immediate, decisive, and large-scale actions are needed to avert climate catastrophe. This essay presumes that democratic governments are best and most desirably positioned to take these actions. Yet in the countries most pivotal to global climate, significant voting blocs are uninterested in environmental issues. The essay urges adding bottom-up dialog between environmental and anti-environmental voters, to current and future top-down technocratic “solutions.” To make this combination result in a unified pro-environment electorate, we must understand: religious objections to environmentalism; the capital-vs.-knowledge strife that slows polluting corporations’ green transitions; and the psychological mechanisms that can make inter-group dialog fruitful.

The greater U.S. Midwest is on the leading edge of tick and tick-borne disease (TBD) expansion, with tick and TBD encroachment into Illinois occurring from both the northern and the southern regions. To assess historical and future habitat suitability of four ticks of medical concern within the state, we fit individual and mean-weighted ensemble species distribution models for Ixodes scapularis, Amblyomma americanum, Dermacentor variabilis, and a newly invading species, Amblyomma maculatum using a variety of landscape and mean climate variables for the periods of 1970-2000, 2041-2060, and 2061-2080. Ensemble model projections for the historical climate were consistent with known distributions of each species but predicted the habitat suitability of A. maculatum to be much greater throughout Illinois than what known distributions demonstrate. Presence of forest and wetlands were the most important landcover classes predicting occurrence of all tick species. As the climate warmed, the expected distribution of all species became strongly responsive to precipitation and temperature variables, particularly precipitation of the warmest quarter and mean diurnal range, as well as proximity to forest cover and water sources. The suitable habitat all species was predicted to shrink in the 2050 climate scenario, and then increase more broadly statewide in the 2070 scenario, but at reduced likelihoods. Predicting where ticks may invade and concentrate as the climate changes will be important to anticipate, prevent, and treat TBD in Illinois.

Pathogenic adenovirus (Ad) infections are widespread but typically mild and transient, except in the immunocompromised. As vectors for gene therapy, vaccine and oncology applications, Ad based platforms offer advantages including ease of genetic manipulation, scale of production and well established safety profiles, making them attractive tools for therapeutic development. However, the immune system often poses a significant challenge that may need to be overcome for adenovirus based therapies to be truly efficacious. Both pre-existing anti-Ad immunity in the population as well as the rapid development of an immune response against engineered adenoviral vectors can have detrimental effects upon the downstream impact of an adenovirus-based therapeutic. This review focusses on the different challenges posed, including pre-existing natural immunity and anti-vector immunity induced by a therapeutic, both in context of the innate and adaptive immune responses. We summarize different approaches developed with the aim of tackling these problems, as well as their outcomes and potential future applications.

At the plasma membrane, transmembrane receptors are at the interface between cells and their environment. They allow sensing and transduction of chemical and mechanical extracellular signals. The spatial distribution of receptors and the specific recruitment of receptor subunits to the cell membrane is crucial for the regulation of signaling and cell behavior. However, it is challenging to define what regulates such spatial patterns for receptor localization, as cell shapes are extremely diverse when cells are maintained in standard culture conditions. Bone morphogenic protein receptors (BMPRs) are serine-threonine kinases, which build heteromeric complexes of BMPRI and II. These are especially interesting targets for receptor distribution studies, since the signaling pathways triggered by BMPR-complexes depends on their dimerization mode. They might exist as pre-formed complexes, or assemble upon binding of BMP, triggering cell signaling which leads to differentiation or migration. In this work we analyzed BMPR receptor distributions in single cells grown on micropatterns, which allows not only to control cell shape, but also the distribution of intracellular organelles and protein assemblies. We developed a script called ComRed (Center Of Mass Receptor Distribution), which uses center of mass calculations to analyze the shift and spread of receptor distributions according to the different cell shapes. ComRed was tested by simulating changes in experimental data, showing that shift and spread of distributions can be reliably detected. Our ComRed-based analysis of BMPR-complexes indicates that receptor distribution depends on cell polarization. The absence of a coordinated internalization after addition of BMP suggests that a rapid and continual recycling of BMPRs occurs. Receptor complexes formation and localization in cells induced by BMP might yield insights into the local regulation of different signaling pathways.

Increased construction activities in Australia have led to the generation of a massive volume of construction and demolition (C&D) waste annually. Management of this volume of waste requires an effective waste framework. The literature reported that the current Australian waste framework does not meet expectations and needs immediate improvements. This study was therefore conducted to seek the key C&D stakeholders' opinion about various issues identified in this waste stream. The specific objectives of this study are identification of the main barriers to effective C&D waste management, the impact of current regulations and opportunities to enhance the current C&D waste management system. A survey was conducted in 2019 to capture the stakeholders' perception. 132 participants from various industries and government agencies based in various Australian jurisdictions took part in the survey. The key results showed that the main barriers towards an effective management system are "overregulation, tough acceptance criteria, and increased testing requirements", "lack of local market" and "culture, poor education and low acceptance". Furthermore, a low number of participants indicated that the current legislation encourages waste recovery activities. The main areas of improvements included "providing a guideline that determines the accepted level of contamination for reusing C&D waste”, "preparation of guidelines on requirements of using recycled C&D materials in different industries" and "setting target for reduction, reusing, and recycling C&D waste". The results can inform policy development and be used as evidence for a broader discussion to solve lasting issues in C&D waste management.

The aim of the scoping review was to map out studies that compared the effect of smoking tobacco and smokeless tobacco on periodontal health. The review was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) framework. The search for articles was conducted in five electronic databases namely: Scopus, CINAHL, Web of Science, Medline, and PubMed. The search yielded two eligible articles for full-text screening. The two studies were cross-sectional in design, conducted in India and they both used bivariate analysis for comparison of the effects of tobacco smoking and the use of smokeless tobacco on the health of the periodontium without adjusting for confounders. The two studies used 10 measures to assess the health of the periodontium namely: Periodontal probing depth, clinical attachment level, gingival index, and periodontal index, plaque index score, debris index score, calculus index score, gingival inflammation, bleeding on probing and pocket depth. Periodontal probing depth, periodontal index, calculus index score and pocket depth worse for tobacco smoking when compared with smokeless tobacco users. Both studies seem to concur on worse pocket depths for tobacco smokers than for users of smokeless tobacco.

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

In an era of unparalleled technical advancement, the pharmaceutical industry is struggling to transform data into increased research and development efficiency, and as a corollary, new drugs for patients. Here, we briefly review some of the commonly discussed issues around this counterintuitive innovation crisis. Looking at both industry and science related factors, we posit that traditional preclinical research is front-loading the development pipeline with data and drug candidates that are unlikely to succeed in patients. Applying a first principles analysis, we highlight the critical culprits and provide suggestions as to how these issues can be rectified through pursuit of a Human Data-driven Discovery (HD3) paradigm. Consistent with other examples of disruptive innovation, we propose that new levels of success are not dependent on new inventions, but rather the strategic integration of existing data and technology assets. In support of these suggestions, we highlight the power of HD3, through recently published proof-of-concept applications in the areas of drug safety analysis and prediction, drug repositioning, rational design of combination therapies and the global response to the Covid19 pandemic. We conclude that innovators must play a key role in expediting the path to a largely human focused, systems-based approach to drug discovery and research.

The association between depressive symptomatology and cognitive decline has been examined using the Centre for Epidemiologic Studies-Depression Scale (CES-D), however, concerns have been raised about this self-report measure. Here, we examined how the CES-D total score from the 14- and 10-item versions compared to the 20-item version in predicting progression to cognitive decline from a cognitively unimpaired baseline. Data from 1,054 participants were analysed using ordinal logistic regression, alongside moderator and receiver-operating characteristics curve analyses. All baseline total scores significantly predicted progression to cognitive decline. The 14-item version was better than the 20-item version in predicting consensus diagnosis, as shown by their AICs, while also showing the highest accuracy when discriminating between participants by diagnosis at last visit. We did not find sex to moderate the relationship between CES-D score and cognitive decline. Current findings suggest the 10- and 14-item versions of the CES-D are comparable to the 20-item version, and that the 14-item version may be better at predicting longitudinal consensus diagnosis compared to the 20-item version.

The study aimed to develop standards for a welfare assessment protocol, by validating potential categorisation thresholds for assessment of beef farms in various beef cow-calf production systems in Namibia. Forty measures combined from a New Zealand-based protocol plus Namibia-specific measures, were applied on 55 beef farms (17 commercial farms, 20 semi-commercial and 18 communal village farms) during pregnancy testing, and a questionnaire guided interview. The categorised measures on a 3-point welfare score of 0: good 1: marginal and 2: poor/unacceptable welfare were subsequently compared with derivation of thresholds based upon the poorest 15% and best 50% of herds for each measure. Overall combined thresholds of continuous measures across the 3 farm types, showed 10/22 measures that posed welfare compromise across Namibia, where commercial farms had 4/22 measures and semi-commercial and communal village farms had 12/22 and 11/22 respectively with high thresholds. Most measures-imposed thresholds were retained because of significant importance to welfare of animals and preventiveness of the traits, while leniency was given to adjust good feeding and mortality measures to signify periods of drought. Handling measures (fearful, falling/lying) and abrasions thresholds were adjusted to reflect the temporary stress caused by infrequent cattle handling, and faulty yard designs/design and possible cattle breed influence on handling. Hence, the country needs prioritised investigation of underlying contributing factors and remediation to reduce the high thresholds.

In this study, we introduce the concept and construction of an innovative Digital Miniature Cathode Ray Magnetometer designed for the precise detection of magnetic fields. This device addresses several limitations inherent to magnetic probes such as D.C. offset, nonlinearity, temperature drift, sensor aging, and the need for frequent recalibration, while capable of oper-ating in a wide range of magnetic fields. The core principle of this device involves the utilization of a charged particle beam as the sensitivity medium. The system leverages the interaction of an electron beam with a scintillator material, which, then, emits visible light that is captured by an imager. The emitted scintillation light is captured by a CMOS sensor. This sensor not only rec-ords the scintillation light but also accurately determines the position of the electron beam, providing invaluable spatial information crucial for magnetic field mapping. The key innova-tion lies in the combination of electron beam projection, CMOS imager scintillation-based de-tection and digital image signal processing. By employing this synergy, the magnetometer achieves remarkable accuracy, sensitivity and dynamic range. The precise position registration enabled by the CMOS sensor further enhances the device's utility in capturing complex magnetic field patterns, allowing for 2D field mapping. In this work, the optimization of the probe's per-formance is tailored for applications related to the characterization of insertion devices in light sources, including undulators.

Background: Myasthenia Gravis (MG) is a rare autoimmune disease presenting with au-to-antibodies that affect the neuromuscular junction. Aside from symptomatic treatment options, novel therapeutics include monoclonal antibodies (mAbs). IMGT®, the international ImMunoGe-neTics information system® (https://www.imgt.org), extends the characterization of therapeutic antibodies with a systematic description of their mechanisms of action (MOA) and makes them available through its database for mAbs and fusion proteins, IMGT/mAb-DB. Methods: Using the available literature data combined with the amino acid sequence analyses from mAbs managed in IMGT/2Dstructure-DB, the IMGT® protein database, biocuration allowed to define in a standardized way descriptions of MOA of mAbs that target molecules towards MG treatment. Results: New therapeutic targets include FcRn and molecules such as CD38, CD40, CD19, MS4A1 and interleukin-6 receptor. A standardized graphical representation of the MOA of selected mAbs was created and integrated within IMGT/mAb-DB. The main mechanisms involved in these mAbs are either blocking or neutralizing. Therapies directed to B cell depletion and plasma cells have a blocking MOA with an immunosuppressant effect along with Fc-effector function (MS4A1, CD38) or FcγRIIb engager effect (CD19). Monoclonal antibodies targeting the complement also have blocking MOA with a complement inhibitor effect and treatments targeting T cells have a blocking MOA with an immunosuppressant effect (CD40) and Fc-effector function (IL6R). On the other hand, FcRn antagonists present a neutralizing MOA with an FcRn inhibitor effect. Conclusion: The MOA of each new mAb needs to be considered in association with the immuno-pathogenesis of each of the subtypes of MG in order to integrate the new mAbs as a viable and safe option in the therapy decision process. In IMGT/mAb-DB, mAbs for MG are characterized by their sequence, domains, chains and their MOA is described.

While there is overwhelming evidence for dark matter (DM) in galaxies and galaxy clusters, all searches for DM particles have so far proved negative. It is not even clear whether only one particle is involved or a combination or particles, their masses not precisely predicted. This non-detectability raises the possible relevance of modified gravity theories – MOND, MONG, etc. Here we consider a specific modification of Newtonian gravity (MONG) which involves gravitational self-energy, leading to modified equations whose solutions imply flat rotation curves and limitations of sizes of clusters. The results are consistent with current observations including that involving large spirals. This modification could also explain the current Hubble tension. We also consider effects of dark energy (DE) in terms of a cosmological constant.

Artisanal and small-scale gold mining (ASGM) has been an important source of income for communities in the Madre de Dios River Basin in Peru for hundreds of years. However, in recent decades, the scale of ASGM activities in the region has increased dramatically, and exposures to a variety of occupational and environmental hazards related to ASGM, including mercury, are becoming more widespread. The aims of our study were to: (1) examine patterns in the total hair mercury level of human participants in several communities in the region and compare these results to the 2.2 µg/g total hair mercury level equivalent to the World Health Organization (WHO) Expert Committee of Food Additives (JECFA)’s Provisional Tolerable Weekly Intake (PTWI); and (2), to measure the mercury levels of paco (Piaractus brachypomus) fish raised in local aquaculture ponds, in order to compare these levels to the EPA Fish Tissue Residue Criterion of 0.3 µg Hg/g fish (wet weight). We collected hair samples from 80 participants in four communities (one control and three where ASGM activities occurred) in the region, and collected 111 samples from fish raised in 24 local aquaculture farms. We then analyzed the samples for total mercury. Total mercury levels in hair were statistically significantly higher in the mining communities than in the control community, and increased with increasing distance away from the Madre de Dios headwaters (as the crow flies), did not differ by sex, and frequently exceeded the reference level. Regression analyses indicated that higher hair mercury levels were associated with residence in ASGM communities. The analysis of paco fish samples found no samples that exceeded the EPA tissue residue criterion. Collectively, these results align with other recent studies showing that ASGM activities are associated with elevated human mercury exposure. The fish farmed through the relatively new process of aquaculture in ASGM areas appeared to have little potential to contribute to human mercury exposure. More research is needed on human health risks associated with ASGM to discern occupational, residential, and nutritional exposure, especially through tracking temporal changes in mercury levels as fish ponds age, and assessing levels in different farmed fish species. Additionally, research is needed to definitively determine that elevated mercury levels in humans and fish result from the elemental mercury from mining, rather than from a different source, such as the mercury released from soil erosion during deforestation events from mining or other activities.

While it is generally accepted that food habits established during infancy will track into later childhood, longitudinal analysis of children’s food preferences is rare. This paper examines whether maternal-reported child food preferences at five years of age are the same as that reported at two years; and identifies any patterns of change from two- to five- years. Mothers in the Australian NOURISH trial reported child food preferences at two and five years of age. A four point scale was utilised - ‘like’, ‘neither like or dislike’, ‘dislike’, ‘never tried’. The proportion of children having the same preference at the two time points was calculated (95%CI) for 48 foods (cereals, 4; vegetables, 20; fruit, 14; meat/alternatives, 6; dairy, 4). For foods where ≤50% children had consistent preferences, the pattern of food preference change was determined. For 40/48 foods, more than half of the children were reported to have the same preference at two years of age, and three years later, at age five. Foods for which ≤50% children had the same preference at both ages were high-sugar breakfast cereals, zucchini, mushrooms, eggplant, spinach, lettuce, cabbage and celery. Findings reinforce the importance of promoting a consistent message regarding early and frequent exposure to a variety of healthy foods, particularly during the first 2 years of life, as the preferences established in these early years are likely to be maintained over time.

A continuous spatio-temporal database of accurate soil moisture (SM) measurements is an important asset for agricultural activities, hydrologic studies, and environmental monitoring. The Advanced Microwave Scanning Radiometer 2 (AMSR2), launched in May 2012, has been providing SM data globally with a revisit period of two days. It is imperative to assess the quality of this data before performing any application. Since resources of accurate SM measurements are very limited in Puerto Rico, this research will assess the quality of the AMSR2 data by comparing with ground-based measurements and perform a downscaling technique to provide a better description of how the sensor perceives the surface soil moisture as it passes over the island. The comparison consisted of the evaluation of the mean error, root mean squared error, and the correlation coefficient. Two downscaling techniques were used and their performances were studied. The results revealed that AMSR2 products tend to underestimate. This is due to the extreme heterogeneous distributions of elevations, vegetation densities, soil types, and weather events on the island. This research provides a comprehensive study on the accuracy and potential of the AMSR2 products over Puerto Rico. Further studies are recommended to improve the AMSR2 products.

Background: Individuals living in rural areas often face challenges in accessing healthcare, increasing their risk of poor health outcomes. Farmers, a sub-population in rural areas, are particularly vulnerable to mental health issues and suicide, yet exhibit low rates of help-seeking behavior. The aim of our study was to develop an in-depth understanding of the issues influencing mental help-seeking among farmers living in rural areas from the perspectives of healthcare providers, as well as to explore the strategies providers use to navigate through these issues to effectively engage with this vulnerable population. Methods: We used a descriptive phenomenological approach to understand healthcare providers’ perspectives, experiences, and approaches to providing mental healthcare to farmer clients in rural areas. Semi-structured interviews were conducted with 21 participants between March and May 2023. Results: Our analysis yielded five thematic areas: (1) ensuring accessibility, (2) establishing relatability, (3) addressing stoicism and stigma, (4) navigating dual roles, and (5) understanding community trauma. Conclusions: Healthcare service delivery for farmers is multifaceted. This study fills a gap in knowledge by translating these the data to inform an evidence-based model and a list of recommendations for implementing agriculturally-informed practices in rural areas.

Cellular biomolecular condensates termed ribonucleoprotein (RNP) granules often are enriched in messenger RNA (mRNA) molecules relative to the surrounding cytoplasm. Yet, the spatial localization and diffusion of mRNAs in close proximity to phase separated RNP granules is not well understood. In this study, we performed single molecule fluorescence imaging experiments of mRNAs in live cells in the presence of two types of RNP granules, stress granules (SG) and processing bodies (PB), which are distinct in their molecular composition and function. We developed a photobleaching- and noise-corrected colocalization imaging algorithm that was employed to determine the accurate positions of individual mRNAs relative to the granule’s boundaries. We found that mRNAs are often localized at granule boundaries, an observation consistent with recently published data. We suggest that mRNA molecules become spontaneously confined at the RNP granule boundary similar to the adsorption of polymer molecules at liquid-liquid interfaces, which is observed in various technological and biological processes. We also suggest that this confinement could be due to a combination of intermolecular interactions associated with, first, the screening of a portion of the RNP granule interface by the polymer and, second, electrostatic interactions due to a strong electric field induced by a Donnan potential generated across the thin interface.

Abstract: Purpose – In this article we lay out the change management practices adopted by financial firms in small states within the Eurozone. We determine whether these organisations have the ability to identify triggers for change (Red Flags) and subject them to eight thematic elements to understand whether management practices can continue to exist and support operational environments, even when unexpected circumstances affect their day to day operations and processes. In doing this we examine the extent to which the eight thematic elements from the model designed by Dalli Gonzi, (2019) (The Dali Model) can assist organisations in risk identification and business continuity planning. Design/methodology/approach – A self-administered questionnaire purposely designed for this study was administered to personnel working in internal controls within financial institutions of small Eurozone states. The participants were asked to grade statements using a 5-point Likert scale, ‘1’ being ‘totally disagree’ and ‘5’ being totally agree’ to the statement posed under the thematic elements forming the basis of the Dali Model. Findings – Factor analysis provided support for the eight hypothesised dimensions of the decision-making model: connection, capacity, governance, network, policy, training, process improvement, standards. Originality/value – The study provides a better understanding and support of “best practice” in change management through an understanding and assessment of the eight factors that are the basis of this model. It addresses practical recommendations to ensure application to a wider frame of use.

Geological disposal facilities for radioactive waste pose significant challenges for robust monitoring of environmental conditions within the engineered barriers that surround the waste canister. Temperatures are elevated, due to the presence of heat generating waste, relative humidity varies from 20% to 100%, and swelling pressures within the bentonite barrier can typically be 2-10 MPa. Here, we test the robustness of a bespoke design MEMS sensor-based monitoring system, which we encapsulate in polyurethane resin. We place the sensor within an oedometer cell and show that despite a rise in swelling pressure to 2 MPa, our relative humidity (RH) measurements are unaffected. We then test the sensing system against a traditional RH sensor, using saturated bentonite with a range of RH values between 50% and 100%. Measurements differ, on average, by 2.87% RH, and are particularly far apart for values of RH greater than 98%. However, bespoke calibration of the MEMS sensing system using saturated solutions of known RH, reduces the measurement difference to an average of 1.97% RH, greatly increasing the accuracy for RH values close to 100%.

Background: Recent infectious disease outbreaks have brought increased attention to strengthening the capacity to prevent, detect, and respond to natural biological threats. However, deliberate biological events also represent a significant global threat that have received relatively little attention. The Biological Weapons Convention provides a foundation for the response to deliberate biological events, but the political mechanisms to respond to and recover from such an event are poorly defined. Methods: We performed an analysis of the epidemiological timeline, the international policies triggered as a notional deliberate biological event unfolds, and the corresponding stakeholders and mandates assigned by each mandate. Findings: The results of this analysis identify a significant gap in both policy and stakeholder mandates: there is no single policy nor stakeholder mandate for leading and coordinating the response activities associated with a deliberate biological event. These results were visualized using an open source web-based tool published at https://dbe.talusanalytics.com. Interpretation: While there are organizations and stakeholders responsible for roles in leading security or public health response, these roles are non-overlapping and are led by organizations not with limited interaction outside such events. The lack of mandates highlights a gap in the mechanisms available to coordinate response and a gap in guidance for managing the response. The results of the analysis corroborate anecdotal evidence from stakeholder meetings and highlight a critical need and gap in deliberate biological response policy.

Structure from Motion with Multi-View Stereo photogrammetry (SfM) is increasingly utilised in geoscience investigations as a cost-effective method of acquiring high resolution (sub-meter) topographic data, but has not been thoroughly tested in gullied savanna systems. The aim of this study was to test the accuracy of topographic models derived from aerial (via an Unmanned Aerial Vehicle, ‘UAV’) and ground-based (via a handheld digital camera, ‘Ground’) SfM in modelling a hillslope gully system in dry-tropical savanna, and to assess the strengths and limitations of the approach at different scales. A UAV survey covered an entire hillslope gully system (0.715 km²), whereas a Ground survey covered a single gully within the broader system (650 m²). SfM topographic models, including Digital Surface Models (DSM) and dense point clouds, were compared against RTK-GPS point data and a pre-existing airborne LiDAR Digital Elevation Model (DEM). Results indicate UAV SfM can deliver topographic models with a resolution and accuracy suitable to define gully systems at a hillslope scale (e.g., 0.1 m resolution with ~ 0.5 – 1.3 m elevation error), while ground-based SfM is more capable of quantifying gully morphology (e.g., 0.01 m resolution with ~ 0.1 m elevation error). Key strengths of SfM for these applications include: the production of high resolution 3D topographic models and ortho-photo mosaics, low survey instrument costs (< $AUD 3,000); and rapid survey time (4 and 2 hours for UAV and Ground survey respectively). Current limitations of SfM include: difficulties in reconstructing vegetated surfaces; uncertainty as to optimal survey and processing designs; and high computational demands. Overall, this study has demonstrated great potential for SfM to be used as a cost-effective tool to aid in the mapping, modelling and management of hillslope gully systems at different scales, in tropical savanna landscapes and elsewhere.

Abstract: 1) Background. This research examined feasibility, acceptability and outcomes of delivering a 6-week yoga-based meditation intervention to clinical teams of hospice professionals (HPs) at a large non-profit hospice organization. The intervention was designed to increase mind-body integration and combat burnout. The manuscript was written for different audiences including research scientists who study interoception, burnout, meditation, or yoga, designers of meditation interventions, and hospice organizations looking for ways to mitigate HP burnout. 2) Methods. The intervention was launched within clinical teams, beginning with a half hour online introduction to the program and exposure to the week 1 meditation at each team’s monthly all-staff meeting. Throughout the program, HPs could access the meditations on their own via their workplace computers, tablets, and smartphones. Online pre- and post-intervention surveys with 151 HPs assessed burnout using the Professional Fulfillment Index and mind-body integration using the Multidimensional Assessment of Interoceptive Awareness sub-scales. 3) Results. Half of HPs expressed a desire to continue to have access to the meditations after the 6-week program ended. Due to covid-19 work from home restrictions, three-fourth of HPs did a meditation at home, 29% in a car between patient visits (not while driving), and 23% at the office. Higher interoceptive awareness was significantly related to lower burnout, particularly lower work exhaustion. Meditation frequency was significantly related to higher interoceptive awareness but not to burnout. 4) Conclusions. Findings showed that yoga-based meditation intervention was feasible and acceptable and associated with higher interoceptive awareness. The results point to a role for interoceptive awareness in reducing the risk for burnout.

In this study, we present a novel approach to estimate the Hurst exponent of time series data using a variety of machine learning algorithms. The Hurst exponent is a crucial parameter in characterizing long-range dependence in time series, and traditional methods such as Rescaled Range (R/S) analysis and Detrended Fluctuation Analysis (DFA) have been widely used for its estimation. However, these methods have certain limitations, which we sought to address by modifying the R/S approach to distinguish between fractional Lévy and fractional Brownian motion, and by demonstrating the inadequacy of DFA and similar methods for data that resembles fractional Lévy motion. This inspired us to utilize machine learning techniques to improve the estimation process. In an unprecedented step, we train various machine learning models, including LightGBM, MLP, and AdaBoost, on synthetic data generated from random walks, namely fractional Brownian motion and fractional Lévy motion, where the ground truth Hurst exponent is known. Meaning that we can initialize and create these stochastic processes with a scaling Hurst/scaling exponent which, is then used as the ground truth for training. Furthermore, we perform the continuous estimation of the scaling exponent directly from the time series, without resorting to the calculation of the power spectrum or other sophisticated preprocessing steps, as done in past approaches. Our experiments reveal that the machine learning-based estimators outperform traditional R/S analysis and DFA methods in estimating the Hurst exponent, particularly for data akin to fractional Lévy motion. Validating our approach on real-world financial data, we observe a divergence between the estimated Hurst/scaling exponents and results reported in the literature. Nevertheless, the confirmation provided by known ground truths reinforces the superiority of our approach in terms of accuracy. This work highlights the potential of machine learning algorithms for accurately estimating the Hurst exponent, paving new paths for time series analysis. By marrying traditional finance methods with the capabilities of machine learning, our study provides a novel contribution towards the future of time series data analysis.

Residential burns camp programmes provide help and support to children with burn injuries by providing activities designed to build their confidence and self-esteem. Our regional burns service has been running camps for over 20 years and evaluation is an important part of assessing their effectiveness. In this study we report both qualitative and quantitative data from 10 consecutive years of burns camps. Qualitative feedback was gathered using Likert scales and free response questionnaires at the end of camp and six weeks post-camp. Three quantitative outcome measures, the Paediatric Quality of Life Inventory v4, the Children’s Revised Impact of Event Scale (CRIES8) and the Satisfaction with Appearance Scale (SWAP) were completed before and six weeks after camp. Children and their parents/carers both reported attending burns camp was helpful for them/their child; the themes of meeting other children with burn injuries and developing confidence and self-esteem were cited as reasons. Parents/carers also reported significant improvements in their child’s physical and psychological functioning post-camp in some years. These findings confirm the importance of providing burns camp programmes for children with burn injuries as part of their post burn rehabilitation.

Election outcomes have been predicted in the past with the help of various state-of-the-art language models. Sentiment analysis helps in establishing the opinions of the public about a particular subject, a popular experiment known as opinion mining. Twitter has grown in popularity and proven to be a key tool in mining people’s sentiments concerning election and other trending subjects of interest. The outcome of the just concluded Presidential election in Nigeria shifts the focus on Lagos State governorship election. In this study, we propose a Bidirectional Encoder Representations from Transformers (BERT) model for the sentiment analysis of governorship election in Lagos State Nigeria using Twitter data. A total of 800,000 personal and public tweets were scraped from twitter concerning the three prominent contesting candidates using carefully selected search queries. The tweets were preprocessed to avoid noise and inconsistencies. The preprocessed tweets were passed into the pretrained and finetuned BERT model. The result was analyzed to establish the sentiments of the public about the candidates. The social networks of the candidates were also analyzed. The parameter-tuning yield different results with different learning rates (LR). Results showed that the learning rate at 1e-7 gave the best performance and that the smaller the learning rate, the higher the accuracy but the larger the epoch size, the higher the accuracy.

Bovine respiratory disease (BRD) is a major health problem within the global cattle industry. This disease has a complex aetiology, with viruses playing an integral role. In this study, metagenomics was used to sequence viral nucleic acids in the nasal swabs of BRD affected cattle. Viruses detected included those well known for their association with BRD in Australia (bovine viral diarrhea virus 1), as well as viruses known to be present but not fully characterised (bovine coronavirus) and viruses that have not been reported in BRD affect cattle in Australia (bovine rhinitis, bovine influenza D, and bovine nidovirus). Nasal swabs from a case control study were subsequently tested for 10 viruses and the presence of at least one virus was found to be significantly associated with BRD. Some of the more recently detected viruses had inconsistent association with BRD. Full genome sequences for bovine coronavirus, a virus increasingly associated with BRD, and bovine nidovirus were complete. Both viruses belong to the Coronaviridae family, which are frequently associated with disease in mammals. This study has provided greater insights into the viral pathogens associated with BRD and highlighted the need for further studies to elucidate more precisely the roles viruses play in BRD.

Effective teamwork is essential to the success of sport and athletic organizations. Interprofessional Collaboration (IPC) and team-based care has also been identified as a priority for health and social care organizations.(World Health Organization, 2010) The Interprofessional Education Collaborative (IPEC) Core Competencies of (1) Values and Ethics; (2) Roles and Responsibilities; (3) Communication; and (4) Teams and Teamwork provide a guiding framework for IPC. (Interprofessional Education Collaborative, 2023). Student-athlete well-being is a key objective for individuals working with or for university athletic departments, with high levels of well-being being correlated with sport, academic, and personal improvements (Navarro et al., 2020). Due to the multifaceted factors that influence student-athlete well-being (e.g., cultural factors, coaches, academic pressure, family stress, etc.), there is an increasing need for an interdisciplinary/interprofessional approach to well-being (Lemelin et al., 2022, Navarro et al., 2020; Ulrich et al., 2022) However, significant barriers exist in implementing IPC into university athletic departments and little research exists on how to overcome roadblocks to integrating IPC in university athletic departments for enhancing student-athlete wellness. This paper will describe how a university athletic department used a team approach to enhance student-athlete health and well-being. The Interprofessional Wellness Team (IWT) included a clinical sport psychology doctoral student, a licensed mental health professional, athletic trainer, and sport dietitian. A case vignette is used to demonstrate how IPEC core competencies are operationalized by the team to address athlete health and well-being through IPC. Recommendations on the further implementation of IPC centered around student-athlete well-being will be provided.

Hypertrophic Cardiomyopathy (HCM) is a common inherited disorder that can lead to heart failure and sudden cardiac death, characterized at the histological level by focal areas of myocyte disarray, hypertrophy and fibrosis, and few disease-targeted therapies exist. To identify, focal, spatially restricted alterations in transcriptional pathways and reveal novel therapeutic targets, we performed a spatial transcriptomic analysis of areas of focal myocyte disarray compared to areas of normal tissue, using a commercially available platform (GeoMx, nanoString). We analyzed surgical myectomy tissue from four patients with HCM and control interventricular septum tissue from two unused organ donor hearts that were free of cardiovascular disease. Histological sections were reviewed by an expert pathologist and 72 focal areas with varying degrees of myocyte disarray (normal, mild, moderate, severe) were chosen for analysis. Areas of interest were interrogated with the Human Cancer Transcriptome Atlas designed to profile 1800 transcripts. Differential expression analysis revealed significant changes in gene expression between HCM and Control tissue, and functional enrichment analysis indicated these genes were primarily involved in interferon production and mitochondrial energetics. Within HCM tissue, differentially expressed genes between areas of mild and moderate disarray were enriched for genes related to mitochondrial energetics (moderate disarray) and response to oxygen/cytokine levels (mild disarray). The comparison between areas of moderate and severe disarray were enriched for genes related to the c-Jun N-terminal kinase (JNK) cascade in severe disarray. Analysis of ligand-receptor pair gene expression revealed that HCM tissue exhibited downregulation of platelet-derived growth factor (PDGF), NOTCH, junctional adhesion molecule, and CD46 signaling, while showing upregulation of fibronectin, CD99, cadherin, and amyloid precursor protein signaling. A deconvolution analysis utilizing the matched single nuclei RNA-sequencing (snRNA-seq) data to determine cell type composition in areas of interest revealed significant differences in fibroblast and vascular cell composition in areas of severe disarray when compared to normal areas in HCM samples. Cell composition in normal areas from control tissue was also divergent from normal areas in HCM samples, which was consistent with the differential expression results. Overall, our data identify novel and potential disease-modifying targets for therapy in HCM.

The reaction of [Co2(CO)8] with an equimolar amount of P(OPh)3] in toluene solution yields in situ generated [Co2(CO)7{P(OPh)3}] 1. Subsequent heating of 1 provides in a condensation reaction an alternative synthetic access to the tetranuclear cluster [{Co4(μ2-CO)3(CO)8{P(OPh)3}] 2. Compound 2 has been characterized by IR and 31P NMR spectroscopy, the tetranuclear cluster framework has be ascertained by a single-crystal X-ray diffraction study performed at 100 K.

The paper proposes a rock classification method using the vibration signal of the rotary drilling process. This proposed method classifies four rocks with a reliability of 100 %, from the vibration signal record of a lasting 1/4 second. For the design of a suitable classification method, several attributes of the vibration signal were calculated for two different signal recording lengths. Cluster dendrogram, ANOVA test, and boxplot were used to determine useful attributes and proper signal length. The classification rule was found using a decision tree, machine learning tool. The publication gradually describes the process of creating the classification method and the results of the reliability verification of the proposed classification method. Rock disintegration by rotary drilling was carried out under standardized experimental conditions. The disintegration rocks were andesite, granite, limestone, and concrete.

We show that an experimentally plausible system consisting of a modulated wire medium hosted in a metal cavity can preserve the longitudinal field profile shaping predicted by Boyd et al. (2018) on the basis of a perfectly periodic wire-only structure. These new frequency domain numerical results are a significant step towards justifying the construction of an experimental apparatus to test the field profile shaping in practise.

Background: Down Syndrome is the most well-studied aneuploidy condition in humans. It is associated with multiple disease phenotypes including cardiovascular, neurological, haemato-logical, and immunological disease processes. In this review paper we aim to discuss the research into gene expression studies performed at the fetal stage of development. Methods: A descriptive review was performed including all papers published on the PubMed database between Septem-ber 1960- September 2022. Results: In the amniotic fluid, genes such as COL6A1 and DSCR1 are affected, causing the phenotypical craniofacial changes. Other genes affected in amniotic fluid in-cluding: GSTT1, CLIC6, ITGB2, C21orf67, C21orf86 and RUNX1. In the placenta, MEST, SNF1LK and LOX were dysregulated, affecting nervous system development. In the brain DYRK1A, DNMT3L, DNMT3B, TBX1, olig2 and AQP4 were found to be dysregulated, affecting the nervous system and intellectual disability. In the cardiac tissues GART, EST2 and ERG found to be dysregulated causing secondary heart field abnormalities. XIST, RUNX1, SON, ERG and STAT1 dysregulated causing myeloproliferative disorders. Conclusions: Differential expression of genes provides clues to the genetic consequences of DS. A better understanding of these processes could eventually to lead to the development of genetic and pharmacological therapies.

The Median American Sign Language Interpretation Software (ASL) Interpretation Software is a web application that is capable of interpreting American Sign Language in real-time, utilizing an internet connection and a primary web camera, complete with basic phrases and letters. Extensive use of Deep Learning and Neural Networks, specifically Convoluted Neural Networks, enables Median to interpret video inputs and generate accurate results directly displayed to the user in text format. The ultimate goal for Median is to have it act as a bridge between hearing people and members of the deaf community, allowing deaf people to communicate with non-signing people using American Sign Language. Furthermore, Median has been designed to benefit people who lack access to a human ASL Translator, as its format as a website allows it to be accessible anywhere at any time, giving increased availability over human interpreters. Median is designed to be a very versatile program with great potential for growth and expansion.

A proposed animal welfare assessment protocol for semi-arid rangeland-based cow-calf systems in Namibia combined 40 measures from a protocol developed for beef cattle in New Zealand with additional Namibia-specific measures. Preliminary validation of the protocol had been undertaken with five herds in one semi-commercial village. The aim of the current study was to apply this protocol and compare animal welfare across three cow-calf production systems in Namibia. A total of 2529 beef cows were evaluated during pregnancy testing in the yards of 17 commercial, 20 semi-commercial and 18 communal (total: 55) herds followed by an assessment of farm resources and a questionnaire-guided interview. Non-parametric tests were used to evaluate the difference in the welfare scores between the production systems. The results indicated a discrepancy of animal welfare between the three farm types, with a marked separation of commercial farms from semi-commercial, and communal village farms in the least. The differences in these production systems was mainly driven by economic gains through access to better beef export market for commercial farms and semi-commercial villages, as well as by the differences in the available grazing land, facility designs/quality and traditional customs in the village systems. The results indicate an advantage of commercialisation over communalisation.

One key area where animal welfare may relate to productivity is through reproductive performance. Welfare was assessed on 25 extensively managed pastoral New Zealand beef farms and the relationship between welfare and reproductive performance was explored. Relationships between welfare measures and key reproductive performance indicators (pregnancy rate, weaning rate, mating period and bull: cow ratio) were investigated using an exploratory Principal Components Analysis and linear regression model. Seven welfare measures (thinness, poor rumen fill, dirtiness, blindness, mortality, health checks of pregnant cows and yarding frequency/year) showed potential influence on reproductive performance, and lameness was retained individually as a potential measure. Mean pregnancy rates in both 2018 (PD18) and 2017 (PD17) were ~91% and mean weaning rate was 84%. Of the welfare measures, only lameness had a direct association with pregnancy rate, as well as confounding effect on the association between mating period and pregnancy rate. The bull: cow ration (mean 1:31) and reproductive conditions (dystocia, abortion, vaginal prolapse) did not influence pregnancy and weaning rates. In the study population there was no clear association between welfare and reproductive performance, except for the confounding effects of lameness.

Trait anxiety, emotion regulation strategies, and metacognitive beliefs influence executive functions (EF) and academic achievement. This study examines their interplay and impact on academic success. In total, 275 adolescents (10-17 years) and parents completed an online questionnaire assessing trait anxiety, emotion regulation strategies, metacognition, parent-reported behaviors related to executive functioning, and overall school average. Preliminary analyses confirmed consistency with existing literature for each variable and their interaction. Furthermore, we conducted a network analysis among the main variables. This analysis supports the need to pay more attention to reflective variables - maladaptive emotion regulation strategies and metacognitive beliefs about worry - when studying trait anxiety. These variables were linked to problematic executive functioning in adolescents. These latter had a negative link to academic achievement. This study offers innovative insights by investigating less-explored relationships in the scientific literature. It reveals high and significant correlations between metacognitive beliefs, maladaptive emotion regulation strategies and trait anxiety (r &gt; .500, p &lt; .001) but also between these variables and both executive functioning and academic achievement. These findings offer new perspectives for research and underscore the importance of holistically examining psychological factors related to academic success.

Rainfall is the main driver of hydrological processes in dryland environments and characterising the rainfall variability and processes of runoff generation are critical for understanding ecosystem function of catchments. Using remote sensing and in situ data sets, we assess the spatial and temporal variability of the rainfall, rainfall-runoff response, and effects of antecedent soil moisture and ground cover at different spatial scales on runoff coefficients in the Upper Burdekin catchment, northeast Australia, which is a major contributor of sediment and nutrients to the Great Barrier Reef. The high temporal and spatial variability of rainfall exerts significant controls on runoff generation processes. Rainfall amount and intensity are the primary runoff controls, and runoff coefficients for wet antecedent conditions were higher than for dry conditions. The majority of runoff occurred via surface runoff generation mechanisms, with subsurface runoff likely contributing little runoff due to the intense nature of rainfall events. At annual to seasonal temporal scales and for relatively large catchments, we could not detect a significant effect of ground cover on runoff. We conclude that in the range of moderate to large catchments (193 – 36,260 km²) runoff generation processes are sensitive to both antecedent soil moisture and ground cover. A higher runoff-ground cover correlation in drier months with sparse ground cover highlighted the critical role of cover at the onset of the wet season and how runoff generation is more sensitive to cover in drier months than in wetter months. The monthly water balance analysis indicates that runoff generation in wetter months (January and February) is partially influenced by saturation overland flow, most likely confined to saturated soils in riparian corridors, swales, and areas of shallow soil. By March and continuing through October, the soil ‘bucket’ progressively empties by evapotranspiration, and Hortonian overland flow becomes the dominant, if not exclusive, flow generation process. The results of this study can be used to better understand the rainfall-runoff relationships in dryland environments and subsequent exposure of coral reef ecosystems in Australia and elsewhere to terrestrial runoff.

The eruption of the COVID-19 pandemic has affected every sphere of life and may forever change how we have always lived and conducted our businesses, and no one can resist the wind of change that is blowing. Of all the sectors of governance, the educational sector, particularly at the tertiary level, appears to have been most greatly affected and therefore requires a more pragmatic approach to resolution. As of 29th June, Sub-Sahara Africa has reported 382,190 cases of COVID-19. In rejoinder to the virus epidemic, several Sub Sahara African governments implement the resolution to slam learning institutions to enclose the infection. Consequently, advanced schooling institutions obliged to reorganize their loom, becoming more digitally become forward, and changing to online platforms.

The Attentional Control Theory (ACT) suggests that trait anxiety does not directly affect performance but may alter processing efficiency through the generation of compensatory strategies. However, the ACT does not describe the nature of these strategies, which could be reflective in nature. One hundred ten students (M = 20.12; SD = 2.10) completed questionnaires on trait anxiety, metacognitive beliefs, and emotion regulation strategies (ERS). They performed two working memory tasks: the digit span task from the WAIS-IV and an emotional n-back task. Anxiety, metacognitive beliefs, and maladaptive ERS were not linked to performance but were associated with longer response times. Additionally, participants using maladaptive ERS, such catastrophizing and rumination, made fewer negative commission errors and employed more strategies during the digit span. These findings support the role of the reflective level in influencing trait anxiety's impact on performance and emphasize considering metacognitive beliefs and maladaptive ERS for a comprehensive understanding of the ACT. Identifying these variables provides insights to optimize cognitive abilities and promote academic success.

We recently found that in human osteoblasts Homer1 complexes to CaSR and mediates AKT initiation via mTORC2 leading to beneficial effects in osteoblasts including -catenin stabilization and mTORC1 activation (doi: 10.1074/jbc.RA118.006587). Herein we further investigated the relationship between Homer1 and CaSR and demonstrate a link between the protein levels of CaSR and Homer1 in human osteoblasts in primary culture. Thus, when siRNA was used to suppress the CaSR, we observed upregulated Homer1 levels and when siRNA was used to suppress Homer1 we observed downregulated CaSR protein levels using immunofluorescence staining of cultured osteoblasts as well as western blot analyses of cell protein extracts. This finding was confirmed in vivo as the bone cells from osteoblast specific CaSR(-/-) mice showed increased Homer1 expression compared to wild-type. Furthermore, when the commonly used osteosarcoma cell lines MG63 and SAOS-2 were compared to primary osteoblasts, higher levels of Homer1 protein were associated with increased protein levels of the CaSR as well as mTOR and Rictor. CaSR and Homer1 protein were both expressed in osteocytes embedded in the long bones of wild-type mice, and immunofluorescent studies of these cells revealed that Homer1 protein sub-cellular localization was markedly altered in the osteocytes of CaSR(-/-) mice compared to wt. The study identifies additional roles for Homer1 in the control of the protein level and subcellular localization of CaSR in cells of the osteoblast lineage, in addition to its established role of mTORC2 activation downstream of the receptor.

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.

How complex morphological patterns form is an intriguing question in developmental biology. However, the mechanisms that generate complex patterns remain largely unknown. Here we sought to identify the genetic mechanisms that regulate the tan (t) gene in a multi-spotted pigmentation pattern on the abdomen and wings of Drosophila guttifera. Previously, we showed that yellow (y) gene expression completely prefigures the abdominal [1] and wing [2] pigment patterns of this species. In the current study, we demonstrate that the t gene is co-expressed with the y gene in nearly identical patterns, both transcripts foreshadowing the adult abdominal and wing melanin spot patterns. We identified cis-regulatory modules (CRMs) of t, one of which drives reporter expression in six longitudinal rows of spots on the developing pupal abdomen, while the second CRM activates the reporter gene in a spotted wing pattern. Comparing the abdominal spot CRMs of y and t, we found a similar composition of putative transcription factor binding sites that are thought to regulate the complex expression patterns of both terminal pigmentation genes y and t. In contrast, the y and t wing spots appear to be regulated by distinct upstream factors. Our results suggest that the D. guttifera abdominal and wing melanin spot patterns have been established through the co-regulation of y and t, shedding light on how complex morphological traits may be regulated through the parallel coordination of downstream target genes.

The advancements achieved in Tissue Engineering are based on a careful and in-depth study of cell-tissue interaction. The choice of a certain biomaterial in Tissue Engineering is fundamental as it represents an interface for adherent cells in the creation of a microenvironment suitable for cell growth and differentiation. The knowledge of the biochemical and biophysical properties of the extracellular matrix is a useful tool for the optimization of polymeric scaffolds. The aim of this re-view is to analyse the chemical, physical and biological parameters on which it is possible to act in Tissue Engineering for the optimization of polymeric scaffolds. Understanding the scaffold impact on cell fate is of paramount importance for the successful advancement of Tissue Engineering.

The amyloid fibril formation by $\alpha$-synuclein is a hallmark of various neurodegenerative disorders, most notably Parkinson's disease. Epigallocatechin gallate (EGCG) has been reported to be an efficient aggregation inhibitor of numerous proteins, among them $\alpha$-synuclein. Here we show that this applies only to a small region of relevant parameter space and that under some conditions, EGCG can even accelerate α-synuclein amyloid fibril formation through facilitating its heterogeneous primary nucleation. Furthermore, we show through quantitative seeding experiments that contrary to previous reports, EGCG is not able to re-model α-synuclein amyloid fibrils into seeding-incompetent structures. Taken together, our results paint a complex picture of EGCG as a compound that can under some conditions inhibit the amyloid fibril formation of α-synuclein, but the inhibitory action is not robust against various relevant changes in experimental conditions. Our results are important for the development of strategies to identify and characterise promising amyloid inhibitors.

The study of rare diseases is important not only for the individuals affected but also for the advancement of medical knowledge and a deeper understanding of human biology and genetics. The wide repertoire of structural information now available from reliable and accurate prediction methods provides the opportunity to investigate the molecular origins of most of the rare diseases reviewed in the Orpha.net database. Thus, it has been possible to analyze the topology of the missense mutations found in the 2,535 proteins involved in Mendelian rare diseases (MRD), which form the database for our structural bioinformatics study. The amino acid substitutions responsible for MRD show different mutation site distributions at different three-dimensional protein depths. We then predicted the depth-dependent effects of mutations for the 20,248 pathogenic variants that are present in our database. The results of this structural bioinformatics investigation are relevant, as they provide additional clues to mitigate the damage caused by MRD.

Introduction: Lipoyl transferase 2 is involved in biosynthesis of the lipoate. Lipoate is the cofactor for the glycine cleavage system and four dehydrogenase enzymes. Biallelic variants in LIPT2 causing severe neonatal encephalopathy was first described in 2017. Methods: Clinical data was collected by retrospective chart review after obtaining consent from parents. The pathogenicity of these variants was further delineated using a yeast model. The YEp352-LIPT2 plasmid was used as a template to generate the two patient variants using QuickChange Lightning Site-Directed Mutagenesis Kit. Results: Patient was a 15-month-old female who presented at 1 month with dystonia, developmental delay and feeding difficulties. MR Brain showed cortical malformations including colpocephaly, polymicrogyria and heterotopia. Patient had elevations in lactate (6.1 mmol/L) and glycine. Exome sequencing showed 2 variants of uncertain significance in trans in the LIPT2 gene: c.346 G>T and c.418C>T. Patient was started on lipoic acid, thiamine and COQ10. Yeast complementation experiments indicate that both patient mutation variants result in diminished function versions of the LIPT2 protein. Conclusion: We report the fourth case of LIPT2-related disorder. Proband shared significant overlap with previous patients, however had a distinct movement disorder and brain malformations which have not been previously described. Unlike most neurometabolic disorders where dystonia develops later after metabolic stroke in basal ganglia, LIPT2- related disorder seems unique due to early onset of dystonia due to energy deficit in the developing brain. Lipoic acid supplementation has not led to significant clinical improvement. Analyses in yeast indicate that novel variants are deleterious but have retained some functionality.

Hispanics are disproportionately affected by low rates of physical activity and high rates of chronic diseases. Hispanics generally and Mexican Americans specifically are underrepresented in research on physical activity and its impact on mental well-being. Some community-based interventions have been effective in increasing physical activity among Hispanics. This study examined data from a sample of low-income Hispanic participants in free community exercise classes to characterize the association between self-reported frequency of exercise class attendance, intensity of physical activity, and participant well-being. As part of two cross-sectional samples recruited from a stratified random sample of community exercise classes, 302 participants completed a questionnaire consisting of a modified version of the Godin-Shephard Leisure-Time Exercise Questionnaire (LTEQ) and the Mental Health Continuum Short Form (MHC-SF). Adjusted binary logistic regression analyses indicated that those who achieve moderate and strenuous self-reported physical activity have 130% higher odds (p = 0.0422) of positive mental well-being after adjustment for age, attendance, and self-reported health. This study provides evidence that physical activity intensity and time are associated with flourishing mental health among Hispanics. The study provides insight into the planning and development of community-based physical activity programming tailored to low-income populations.

Barth Syndrome, a rare X-linked disorder affecting 1:300,000 live births, results from defects in Tafazzin, an acyltransferase that remodels cardiolipin and is essential for mitochondrial respiration. Barth Syndrome patients develop cardiomyopathy, muscular hypotonia and cyclic neutropenia during childhood, rarely surviving to middle age. At present, no effective therapy exists and downstream transcriptional effects of Tafazzin dysfunction are incompletely understood. To identify novel, cell-specific, pathological pathways that mediate heart dysfunction, we performed single-nucleus RNA-sequencing (snRNA-seq) on wild-type (WT) and Tafazzin-knockout (Taz-KO) mouse hearts. We determined differentially expressed genes (DEGs) and inferred predicted cell-cell communication networks from these data. Surprisingly, DEGs were distributed heterogeneously across the cell types, with fibroblasts, cardiomyocytes, endothelial cells, macrophages, adipocytes and pericytes exhibiting the greatest number of DEGs between genotypes. One differentially expressed gene was detected for the lymphatic endothelial and mesothelial cell types, while no significant DEGs were found in the lymphocytes. A Gene Ontology (GO) analysis of these DEGs showed cell-specific effects on biological processes such as fatty acid metabolism in adipocytes and cardiomyocytes, increased translation in cardiomyocytes, endothelial cells and fibroblasts, in addition to other cell-specific processes. Analysis of ligand-receptor pair expression, to infer intercellular communication patterns, revealed the strongest dysregulated communication involved adipocytes and cardiomyocytes. For the knockout hearts, there was a strong loss of ligand-receptor pair expression involving adipocytes, and cardiomyocyte expression of ligand-receptor pairs underwent reorganization. These findings suggest that adipocyte and cardiomyocyte mitochondria may be most sensitive to mitochondrial Tafazzin deficiency and that rescuing adipocyte mitochondrial dysfunction, in addition to cardiomyocyte mitochondrial dysfunction, may provide therapeutic benefit in Barth Syndrome patients.

The primary cilium plays critical roles in homeostasis and development of neurons. Recent studies demonstrate that cilia length is regulated by the metabolic state of cells, as dictated by processes such as glucose flux and O-GlcNAcylation (OGN). The study of cilia length regulation during neuron development, however, has been an area left largely unexplored. This project aims to elucidate the roles of O-GlcNAc in neuronal development through its regulation of the primary cilium. Here, we present findings suggesting that OGN levels negatively regulate cilia length on differentiated cortical neurons derived from human-induced pluripotent stem cells. In neurons, cilia length increased significantly during neurons maturation (after day 35), while OGN levels began to drop. Long-term perturbation of OGN via drugs, which inhibit or promote its cycling, during neuron development also have varying effects. Diminishing OGN levels increases cilia length until day 25, when neural stem cells expand and undergo early neurogenesis, before causing cell cycle exit defects and multinucleation. Elevating OGN levels induces greater primary cilia assembly but ultimately results in the development of premature neurons, which have higher insulin sensitivity. These results indicate that OGN levels and primary cilia length are jointly critical in proper neuron development and function. Understanding the interplays between these two nutrient sensors, O-GlcNAc and the primary cilium, during neuron development is important in paving connections between dysfunctional nutrient-sensing and early neurological disorders.

The standard of care for nonoperative appendicitis patients involves ongoing antibiotic therapy. Yet, there is variability regarding the decision to continue outpatient parenteral antibiotic treatment (OPAT) or transition to oral (PO) antibiotics. Methods: In our single-center retrospective study, we reviewed 46 pediatric patients who underwent nonoperative management of perforated appendicitis with Interventional Radiology (IR) percutaneous drainage. We reviewed age, ethnicity, hospitalization length, antibiotic choice, route and duration, and culture data. Results. Thirty-eight [83%] patients went home on OPAT, 6[13%] on PO, and 2[4%] completed therapy while inpatient. Based on culture susceptibilities of the 38 OPAT patients, 29[76%] had oral antibiotics as an option. The three most common organisms in those sent home on OPAT included Enterococcus faecalis (38 [100%]), Bacteroides spp (33 [87%]) and Escherichia coli (27 [71%]). All patients who grew Pseudomonas aeruginosa had an oral antibiotic as a treatment option; similarly with 93% (25/27) of E. coli, 81% (13/16) of α-hemolytic Streptococcus spp, and 76% (29/38) of Enterococcus faecalis.  Conclusions:  Nearly 80% of patients sent home on OPAT had PO antibiotic regimens options based on the culture susceptibility profiles. This data indicates that using cultures and susceptibility data can help guide antibiotic management, significantly reducing PICC line placement and likely reduce healthcare costs and complications associated with central lines.

Seed bank survival underpins plant population persistence but studies on seed bank trait-environment interactions are few. Changes in environmental conditions relevant to seed banks occur in desert ecosystems owing to solar energy development. We developed a conceptual model of seed bank survival to complement methodologies using in-situ seed bank packets. Using this framework, we quantified the seed bank survival of two closely related annual desert plant species, one rare (Eriophyllum mohavense) and one common (Eriophyllum wallacei) and the seed bank-environment interactions of these two species in the Mojave Desert within a system that emulates microhabitat variation associated with solar energy development. We tracked 4,860 seeds buried across 540 seed packets and found, averaged across both species, that seed bank survival was 21% and 6% for the first and second growing seasons, respectively. After two growing seasons, the rare annual had a significantly greater seed bank survival (10%) than the common annual (2%). Seed bank survival, across both species, was significantly greater in Shade (10%) microhabitats compared to Runoff (5%) microhabitats and Control microhabitats (3%). Our study confers insight into this early life-stage across rare and common congeners and their environmental interactions using a novel conceptual framework for seed bank survival.

Conjugation is a bacterial mechanism for DNA transfer from a donor cell to a wide range of recipients, including both prokaryotic and eukaryotic cells. In contrast to conventional DNA delivery techniques, such as electroporation and chemical transformation, conjugation eliminates the need for DNA extraction, thereby preventing DNA damage during isolation. While most established conjugation protocols allow for DNA transfer in liquid media or on a solid surface, we developed a procedure for conjugation within solid media. Such a protocol may expand conjugation as a tool for DNA transfer to species that require semi-solid or solid media for growth. Conjugation within solid media could also provide a more stable microenvironment in which the conjugative pilus can establish and maintain contact with recipient cells for the successful delivery of plasmid DNA. Furthermore, transfer in solid media may enhance the ability to transfer plasmids and chromosomes greater than 100 kbp. Using our optimized method, plasmids of varying sizes were tested for transfer from E. coli to S. cerevisiae. We demonstrated that there was no substantial decrease in conjugation frequency as plasmid size increased—up to 138.5 kbp in length. Finally, we established an efficient PCR-based synthesis protocol to generate custom conjugative plasmids

The responses of inflammatory cytokines and brain-derived neurotrophic factor (BDNF) to a high-intensity interval training (HIIT) session were compared between 7 postmenopausal (57±2 y) and 8 premenopausal females (44±3 y) during the luteal phase of their menstrual cycle, when estrogen and progesterone are highest, and. HIIT consisted of 10 x 1 min running intervals (90% maximum heart rate) separated by 1 min recovery intervals. Blood samples were collected at baseline (fasted), pre-exercise (postprandial), and 0, 30 and 90 min post-HIIT and analyzed for interleukin (IL-6) and 10 (IL-10), tumour necrosis factor-alpha (TNF-α) and BDNF. IL-6 significantly increased from pre-exercise to 0 min post-HIIT in postmenopausal (+40%, p=0.01) but 30 min post-HIIT in premenopausal females (+60%, p=0.02). IL-6 remained elevated at 90 min post-HIIT in premenopausal (+104%, p=0.05) and to a higher degree in postmenopausal (+385%, p&lt;0.001). IL-10 showed no response. TNF-α increased from pre- to 0 min post-HIIT (+10%, p=0.05), then decreased to below pre-exercise at 30 min (-10%, p=0.02) and 90 min (-5%, p=0.04) in both groups. BDNF increased immediate post-HIIT in premenopausal (+60%, p&lt;0.001) but not postmenopausal females. The differences in IL-6 and BDNF response to HIIT between pre and postmenopausal females provide evidence of the role of female reproductive hormones in the regulation of these exercise-induced responses.

Coastal flooding exacerbated by climate change is recognised as a major global threat which is expected to impact more than a quarter of people currently residing in Pacific Islands countries. While most research in the last decade has focused on understanding the dynamics and impacts of future coastal flooding from extreme sea levels, relative sea level rise (RSLR) effects on tsunami hazards are not well understood. Far-field or distant-sourced tsunamis tend to have relatively lower impacts in Pacific Island states compared with locally sourced events, but there is limited understanding on how the impact of far-field tsunamis changes over time due to RSLR. Using the hydrodynamics software BG-Flood, we modelled the Tōhoku tsunami from propagation to inundation in Samoa under incremental SLR to examine the effects that RSLR has on changing the exposure of the built environment (e.g., buildings) to a far-field tsunami. Outputs of maximum tsunami inundation and flow depth intensities which incorporate incremental SLR were then combined with digital representations of buildings and depth-damage functions in the RiskScape multi-hazard risk modelling software to assess the changes in building exposure over time. Results indicate that present day buildings exposure in Samoa to a Tōhoku-oki type far-field tsunami will increase by approx. 600% with 1 m RSLR by 2080–2130, and approx. 2,350% with 2 m RSLR by 2130–2140. These findings provide a useful baseline for tsunami hazard risk assessment under changing sea level conditions in analogous island environments.

The development of CRISPR associated proteins, such as Cas9, has led to increased accessibility and ease of use in genome editing. However, additional tools are needed to quantify and identify successful genome editing events in living animals. We developed a method to rapidly and quantitatively monitor gene editing activity non-invasively in living animals that also facilitates confocal microscopy and nucleotide level analyses at the end of study. Here we report a new CRISPR “footprinting” approach to activate luciferase and fluorescent proteins in mice as a function of gene editing. This system is based on experience with our prior Cre-detector system and is designed for Cas editors able to target LoxP including gRNAs including SaCas9 and ErCas12a [1, 2]. These CRISPRs cut specifically within LoxP, an approach that is a departure from previous gene editing in vivo activity detection techniques that targeted adjacent stop sequences. In this sensor paradigm, CRISPR activity was monitored non-invasively in living Cre reporter mice (FVB.129S6(B6)-Gt(ROSA)26Sortm1(Luc)Kael/J and Gt(ROSA)26Sortm4(ACTB-tdTomato,-EGFP)Luo/J, which will be referred to as LSL and mT/mG throughout the paper) after intramuscular or intravenous hydrodynamic plasmid injections, demonstrating utility in two diverse organ systems. The same genome-editing event was examined at the cellular level in specific tissues by confocal microscopy to determine the identity and frequency of successfully genome-edited cells. Further, SaCas9 induced targeted editing at efficiencies that were comparable to Cre recombinase demonstrating high effective delivery and activity in a whole animal. This work establishes genome editing tools and models to track CRISPR editing in vivo non-invasively and to fingerprint the identity of targeted cells. This approach also enables similar utility for any of the thousands of previously generated LoxP animal models.

This paper focuses on quantifying the economic and financial viability of NB-IoT and LoRaWAN technologies, two low-power wide-area network (LPWAN) technologies with unique characteristics that make them suitable for IoT applications. The purpose of the study is to propose an artefact for performing life cycle cost analysis and demonstrate its application to these technologies. The methodology uses pragmatic computational tools to facilitate the analysis and considers all relevant economic and financial factors, such as operating costs, equipment costs, and revenue potential. The main finding of the study is that NB-IoT and LoRaWAN technologies have different cost structures and revenue potentials, which may affect their economic and financial viability for different IoT applications. Ultimately, the study concludes that a comprehensive life cycle cost analysis is critical to making informed decisions about technology adoption, and that the proposed methodology can be applied to other IoT technologies to gain insight into their economic and financial viability.

The COVID-19 pandemic underscores the significance of vaccine hesitancy in shaping vaccination outcomes. Understanding the factors underpinning COVID-19 vaccination hesitancy is crucial for tailoring effective vaccination strategies. This cross-sectional study, conducted in three communities across the United States and Lebanon, employed surveys to assess respondents' knowledge, attitudes, and perceptions regarding COVID-19 infection and vaccination. Among the 7,196 participants, comprising 6,775 from the US and 422 from Lebanon, vaccine hesitancy rates were comparable at 12.2% and 12.8%, respectively. Notably, a substantial proportion of respondents harbored misconceptions, such as attributing the potential to alter DNA (86.4%) or track individuals (92.8%) to COVID-19 vaccines, and believing in the virus's artificial origins (81%). Primary determinants of hesitancy included perceptions that the vaccine poses greater risk than the infection itself (aOR = 8.7 and 9.4, respectively) and negative recommendations from healthcare providers (aOR = 6.5 and 5.4, respectively). Conversely, positive endorsements from healthcare providers were associated with reduced hesitancy (aOR = 0.02 and 0.4, respectively). Targeting healthcare providers to dispel misinformation and elucidate COVID-19 vaccine risks holds promise for enhancing vaccination uptake.

Little is known about how internal positive psychological resources, such as hope, impact burden in family caregivers of persons with dementia. The current study is novel in that it examined how multiple dimensions of hope impacted perceived burden in a sample of family caregivers of persons with Alzheimer’s disease. The stress process model was used as the theoretical framework for variable specification in this study of one-hundred and fifty-five caregivers. Multiple regression was used to determine if hope-agency and hope-pathway independently contributed to burden. Mediation analysis was used to assess whether hope mediated the relationship between subjective stress and burden. Hope-agency but not hope-pathway influenced burden when other variables were considered. Hope-agency partially mediated the effect of subjective stress on burden. This study provides evidence for the relevance of assessing multiple hope dimensions when working with caregivers. It also speaks to the importance of developing/testing hope-bolstering clinical interventions for this population.

The brief paper utilises Zimbabwe as a case study to discuss the effects of El Nino in Southern Africa. It offers potential adaptation and mitigation measures for farmers to prepare for the forecasted El Nino-influenced rainy season 2023/24 and the future. To reduce climate and weather hazards connected with El Nino, the brief report suggests anticipatory action methods be applied in southern Africa, using Zimbabwe as a case study. To protect farmers' livelihoods and enhance drought readiness for the forthcoming agricultural seasons, the paper suggests a degree of strategic, tactical, and operational decision-making that the agriculture industry should adhere to. It emphasised the significance of providing farmers with knowledge and advice regarding drought and heat stress, including cultivating crop varieties and livestock and sufficient fire safety precautions. The brief paper calls to advocate for anticipatory action to avert El Nino in Southern Africa.

Water-soluble nonionic surfactant, pentaethylene glycol monododecyl ether, C12E5, spontaneously blooms to the surface of spin-cast hydrophobic polyiso-prenes, generating hydrophilic surfaces. This system represents a simple model for hydrophilic chemical modification of rubbery polymers yet demonstrates surprisingly rich, complex and unexpected behaviour. The ver-tical depth profiles were quantified using neutron reflectometry (NR) and deuterated surfactant, and the surface properties were characterized using con-tact angle analysis and atomic force microscopy (AFM). Despite the low surface tension of the toluene solvent used in film preparation and the low surface en-ergy of the PI matrix, NR depth profiles revealed clear evidence of surfactant segregation. This surface layer was typically thicker than a monolayer, but incomplete, yet was remarkably stable with respect to dissolution, even when exposed to hundreds of thousands of times the volume of water required to dissolve all the surfactant on the surface. Despite the apparent resistance to removal from the surface, water exposure does alter the subsequent wettabil-ity of the surface, with a hydrophilic-to-hydrophobic transition occurring after rinsing. Complementary AFM images of these C12E5 / cis-PI films showed unexpected strand-like features on the surface of the film, which we attribute to a non-uniform lateral distribution of some of the surfactant. This surface structure becomes more evident after rinsing, and it appears that there are two distinct populations of surfactant on the PI film surface. We conclude that some of the bloomed surfactant exists as layers, which are relatively inert with respect to rinsing or surface modification, and some is laterally inhomogene-ous. This latter population is primarily responsible for surface wetting be-havior, but is not detected by specular NR.

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

Human Cytomegalovirus (HCMV) infection is a serious complication in hematopoietic stem cell transplant (HSCT) recipients due to virus-induced myelosuppression and impairment of stem cell engraftment. Despite the clear clinical link between myelosuppression and HCMV infection, little is known about the mechanism(s) by which the virus inhibits normal hematopoiesis because of the strict species specificity and the lack of surrogate animal models. In this study, we developed a novel humanized mouse model system that recapitulates the HCMV-mediated engraftment failure after hematopoietic cell transplantation. We observed significant alterations in the hematopoietic populations in peripheral lymphoid tissues following engraftment of a subset of HCMV+ CD34+ HPCs within the transplant suggesting that a small proportion of HCMV-infected CD34+ HPCs can profoundly affect HPC differentiation in the bone marrow microenvironment. This model will be instrumental to gain insight into the fundamental mechanisms of HCMV myelosuppression after HSCT and provides a platform to assess novel treatment strategies.

Background: Dietary quality and the consumption of antioxidant-rich foods has been shown to protect against memory decline. Therefore, this double-blind, randomized, placebo-controlled study aimed to investigate the effects of a nutritional supplement on changes in cognitive performance. Methods: In adults aged 40 to 70 years with subjective memory complaints, participants were randomly allocated to take a supplement containing vitamin E, astaxanthin, and grape juice extract daily for 12 weeks or a matching placebo. The primary outcomes comprised changes in cognitive tasks assessing episodic memory, working memory, and verbal memory. Secondary and exploratory measures included changes in the speed of information processing, attention, and self-report measures of memory, stress, and eye and skin health. Moreover, changes in plasma concentrations of brain-derived neurotrophic factor, malondialdehyde, tumor-necrosis factor-α, and interleukin-6 were measured, along with changes in skin carotenoid concentrations. Results: compared to the placebo, nutritional supplementation was associated with larger improvements in episodic memory, a self-report measure of everyday memory, increased plasma brain-derived neurotrophic factor, decreased plasma malondialdehyde, and increased skin carotenoid concentrations. However, there were no group differences in changes in the remaining outcome measures. Conclusions: Twelve weeks of supplementation with a nutritional supplement was associated with improvements in episodic memory and several biological markers associated with cognitive health. Future research will be essential to extend and validate the current findings.

Procedural Sedation and Analgesia (PSA) in the Emergency Department (ED) presents a crucial aspect of emergency medicine, enabling the execution of painful or distressing procedures with minimal patient discomfort. This narrative review delineates the pharmacological framework, methodologies, and clinical considerations integral to optimizing PSA, with a particular focus on pediatric and geriatric populations. Through a comprehensive review and analysis of current practices, this work evaluates the pharmacokinetics and pharmacodynamics of widely utilized sedatives and analgesics, including propofol, ketamine, dexmedetomidine, fentanyl, midazolam, etomidate, nitrous oxide, and remimazolam. Special attention is dedicated to the selection criteria based on patient-specific risk factors, procedural requirements, and the management of potential adverse effects. The manuscript also explores innovative sedation techniques and the integration of new pharmacological agents, emphasizing evidence-based approaches to enhance patient safety and outcome. Results underscore the significance of tailored sedation strategies, especially for vulnerable groups such as pediatric and geriatric patients, highlighting the need for meticulous pre-procedural assessment and monitoring to mitigate risks. Conclusions drawn advocate for a nuanced application of PSA, guided by current evidence and clinical guidelines, to improve the quality of care in emergency settings. This research reinforces the imperative for ongoing education, skill development, and adaptation of new evidence into clinical practice to advance procedural sedation and analgesia in the ED.

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in the alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more response in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.

Current methodologies for developing patient-derived xenografts (PDX) in humanized mice in preclinical trials to test response to immune-based therapies are limited by graft versus host disease. Here we compared two approaches for establishing PDX tumors in humanized mice: 1) PDX are first established in immune-deficient mice; 2) PDX are initially established in humanized mice, before transplanting established PDX’s to a larger cohort of humanized mice for preclinical trials. With the first approach, there was rapid wasting of PDX-bearing humanized mice with high levels of activated T cells in the circulation and organs, indicating immune-mediated toxicity. In contrast, with the second approach, toxicity was less of an issue and long-term human melanoma tumor growth and maintenance of human chimerism was achieved. Pre-clinical trials from the second approach revealed that rigosertib, but not anti-PD-1, increased CD8/CD4 T cell ratios in spleen and blood and inhibited PDX tumor growth. Resistance to anti-PD-1 was associated with limited infiltration of CD8+ T cell into the tumor. Our findings suggest that it is essential to carefully manage immune editing by first establishing PDX tumors in the presence of human immune cells before expanding PDX tumors into a larger cohort of humanized mice to evaluate therapy response.

The profile of secondary metabolites occurring in apple cuticular layer is not only characteristic for particular apple cultivar, but also dynamically reflects various external factors in growing environment. In this study, the possibility to authenticate apple samples based on analysis of their cuticular layer extracts was investigated. Ultra-high-performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-HRMS/MS) was employed for obtaining metabolomic fingerprints. In total, 274 authentic apple samples, four cultivars harvested within the seasons 2020 to 2022 in the Czech Republic and Poland were analysed. The generated complex data processed by univariate and multivariate statistical methods enabled to build classification models for discrimination of apple cultivars as well as their geographical origin. The models showed very good performance in differentiation of Czech and Polish samples for three of four cultivars: ‘Gala’, ‘Golden Delicious’ and ‘Idared’, moreover, the validity of the models was verified over harvest seasons. The diagnostic markers, besides metabolites of triterpene biosynthetic pathway, mainly represented wax esters. ‘Jonagold’, which is known to be susceptible to mutations, was the only cultivar for which the unambiguous classification of geographical origin was not possible.

Strawberry root rot caused by Neopestalotiopsis clavispora is one of the main diseases of strawberry and significantly impacts the yield and quality of strawberry fruit. There are now no effective control techniques available except for fungicide sprays, which may directly impact consumers. Biological control is becoming an alternative method for the control of plant diseases to replace or decrease the application of traditional synthetic chemical fungicides. Trichoderma is widely used as a biological agent for controlling strawberry root rot. In order to provide resources for screening the highly effective biocontrol fungus for controlling strawberry root rot caused by Neopestalotiopsis clavispora, the biocontrol mechanism,the control effects of Trichoderma asperellum CMT10 against strawberry root rot and growth-promoting effects on strawberry seedlings were investigated by plate culture, microscopy observation and root drenching methods.The results showed that CMT10 had obvious competitive, antibiotic and hyperparasitism effects on Neopestalotiopsis clavispora CMGF3. The CMT10 could quickly occupy nutritional space, and the inhibition rates of CMT10 against CMGF3 in confrontation culture on 7 d was 65.49%. The inhibition rates of volatile metabolite and fermentation metabolite produced by CMT10 against CMGF3 were 79.67% and 69.84%, respectively. The mycelium of strain CMT10 can act as hyperparasites by making contacting, winding and penetrating hyphae of CMGF3. Pot experiment showed that the biocontrol efficacy of CMT10 on strawberry root rot caused by Neopestalotiopsis clavispora was 63.00%. CMT10 had obvious promotion effect on strawberry growth, the plant height, root length, total fresh weight, root fresh weight, stem fresh weight and root dry weight, with the promotion rates were 20.09%, 22.39%, 87.11%, 101.58%, 79.82% and 72.33%, respectively. Overall, this study showed the ability of Trichoderma asperellum CMT10 to control strawberry root rot and their potential to develop as novel biocontrol agents to replace chemical fungicides for eco-friendly, sustainable agriculture.

Apis mellifera, especially weak ones, are highly vulnerable to Carpoglyphus lactis mites, which can rapidly infest and consume stored pollen, leading to weakened colonies and potentially colony collapse. This study aimed to ascertain and investigate the prevalence of this mite in honeybee colonies across 9 provinces in the Republic of Korea (ROK). A total of 615 honeybee colonies were collected, from 66 apiaries during the spring and 58 apiaries during the summer of 2023. A 1,242 bp segment of the the Cytochrome c oxidase subunit 1 (COI) gene was amplified using the polymerase chain reaction method. The detection levels of C. lactis in the honeybees were compared between winter and summer. Based on the COI sequence analysis, the nucleotide sequence similarity of C. lactis mites isolated in the ROK with those from China (NC048990.1) was found to be 99.5%, and with those from the United Kingdom (KY922482.1) was 99.3%. This study is the first report of C. lactis in Korean apiaries. The findings in this study demonstrate a significantly higher detection rate in winter, which is 4.1 times greater than that in summer (p &lt; 0.001). Furthermore, the results underscore the usefulness of molecular diagnostic techniques for detecting C. lactis mites.

COX II containing a dual core CuA active site is one of the three core subunits of mitochondrial Cco, which plays a significant role in the physiological process. In this report, the full-length cDNA of COXⅡ gene was cloned from Sitophilus zeamais, which had an ORF of 684 bp encoding 227 amino acids residues. The predicted COXⅡ protein had a molecular mass of 26.2 kDa with pI value of 6.37, and multiple sequence alignment and phylogenetic analysis indicated that Sitophilus zeamais COXⅡ had high sequence identity 78.51% with the COXⅡ of other insect species, especially similarity to sitophilus oryzae. This gene was subcloned into the prokaryotic expression vector pET-32a, and induced by IPTG in E.coli Transetta (DE3) expression system. Finally the COXⅡ with 6-His tag was purified using affinity chromatography with Ni²⁺-NTA agarose. WB showed the recombinant COXⅡ was about 44 kD, and the concentration of fusion protein was 50μg/mL. UV-spectrophotometer and infrared spectrometer analysis showed that recombinant COXⅡ could catalyze the oxidation of substrate Cytc, and influenced by AITC. It was found that AITC could form a hydrophobic region with COXⅡ protein via molecular docking, besides, a sulfur atom of AITC structure could form a length of 2.9 Å hydrogen bond with Leu-31. These results will provide valuable information for elucidating the role of COXⅡ in Sitophilus zeamais responses to AITC, meanwhile, it will helpful to carry out a point mutation in AITC binding sites for the future research.