Progressive supranuclear palsy (PSP) is a sporadic parkinsonism tauopathy characterised by the deposition of aggregations of abnormal, hyperphosphorylated four-repeat tau (4R-tau). A revised clinical diagnostic criterion for PSP allows early presentations for the full spectrum of clinical phenotypes to be recognised enabling doctors to make a more accurate diagnosis. The major genetic risk factor for sporadic PSP is a common variant in the gene encoding microtubule-associated protein tau (MAPT). Research into the biochemical and pathological pathways of tau is vital to improve the chances of developing an effective diagnostic biomarker to monitor tau pathogenesis. Neuroimaging biomarkers, such as tau PET ligands, are proving the most successful tool in providing a differential diagnosis between neurodegenerative disorders. There are currently no effective treatments for PSP, however tau-directed therapies in the last five years have rapidly advanced. Latest tau therapies are proposed to have disease-modifying effects by reducing toxic aggregations of tau through manipulating tau gene expression. After encouraging results from long awaited trials, additional funding is being injected into this field and with new results expected, this proves an exciting area for scientific discovery. This paper reviews advances in pathophysiology, diagnosis, biomarkers and disease-modifying therapeutic treatments for PSP.

Preeclampsia is a complex pregnancy-related hypertensive disorder which poses significant risks for both maternal and fetal health. Preeclampsia affects 5-8% of the pregnancies in the United States, causing a significant public health and economic burden. Despite extensive research, the etiology and pathogenesis of preeclampsia remain elusive, but have been correlated with maternal conditions such as obesity. In the past decades, the incidence of preeclampsia increased along with the prevalence of obesity among women of reproductive age. Maternal obesity has been shown to negatively affect pregnancy in almost all aspects. However, the precise mechanisms by which obesity influences preeclampsia are unclear. Ankyrin repeat and SOCS Box Containing protein 4 (ASB4) is an E3 ubiquitin ligase that can promote the degradation of a wide range of target proteins. ASB4-null mice display a full spectrum of preeclampsia-like phenotypes during pregnancy including hypertension, proteinuria, and decreased litter size. Furthermore, maternal obesity induced by a high fat diet aggravates preeclampsia-like phenotypes in pregnant mice lacking ASB4. Variants in the ASB4 gene have been associated with obesity in humans, and a functional connection between the ASB4 gene and obesity has been established in mice. This review discusses the connections between preeclampsia, obesity, and ASB4.

We give a bilocal field theory description of a composite scalar with an extended binding potential, that reduces to the Nambu–Jona–Lasinio (NJL) model in the pointlike limit. This provides a description of the internal dynamics of the bound state and features a static internal wave-function, ϕ(⃗r), in the center-of-mass frame that satisfies a Schr¨odinger-Klein-Gordon equation with eigenvalues m2. We analyze the “coloron” model (single perturbative massive gluon exchange) which yields a UV completion of the NJL model. This has a BCS-like enhancement of its interaction, ∝ Nc the number of colors, and is classically critical with gcritical remarkably close to the NJL quantum critical coupling. Negative eigenvalues for m2 lead to spontaneous symmetry breaking, and the Yukawa coupling of the bound state to constituent fermions is emergent.

We investigate solutions of the classical Mathieu-Hill (MH) equation which characterizes the dynamics of trapped ions, based on the Floquet theory and starting from a well known analytical model. The analytical model we introduce demonstrates that the equations of motion are equivalent to those of the harmonic oscillator (HO). Two independent approaches are used, based on two classes of complex solutions of the MH equation. The paper addresses both the damped HO and parametric oscillator (PO) for an ion confined in an electrodynamic (Paul) trap. Stability and instability regions for the periodic orbits associated to the MH equation which describes a HO (PO) confined in an electrodynamic trap are also discussed, depending on the values of the Floquet exponent, for very small values of the $q$ parameter. The main objective of the paper is to identify stable and bounded solutions for the dynamics of a HO levitated in an electrodynamic trap. This paper represents a follow-up of a recently published article in Photonics, 11 (6) 551.

The stability properties of the Hill equation are discussed, and especially those of the Mathieu equation that characterize ion motion in electrodynamic traps. The solutions of the Mathieu equation for a trapped ion are characterized by using the Floquet theory and Hill's Method solution, which yields an infinite system of linear and homogeneous equations whose coefficients are recursively determined. Stability is discussed for parameters $a$ and $q$ that are real. Characteristic curves are introduced naturally by the Sturm-Liouville problem for the well known even and odd Mathieu equations $ce_m(z,q)$ and $se_m(z,q)$. We illustrate the stability diagram for a combined (Paul and Penning) trap and represent the frontiers of the stability domains for axial and radial motion. In case of a Paul trap the stable solution corresponds to a superposition of harmonic motions. The problem of evaluating the maximum amplitudes of stable oscillations for the ideal conditions (taken into consideration) is also approached. Anharmonic corrections are discussed within the frame of the perturbation theory, while the frontiers of the modified stability domains are determined as a function of the chosen perturbation parameter. The results apply to 2D and 3D ion traps used for different applications in quantum engineering, among which optical clocks, quantum logic and quantum metrology, but not restricted only to these.

A simple underwater noise model suitable for use with explosive severance of well conductors and piles during the decommissioning of oil and gas subsea structures is introduced and evaluated against data from five projects in the US. This study focuses on a novel model for the determination of sound exposure levels. The model has been developed to enable determination of impact areas for marine mammals and fish. Simulated received underwater sound exposure levels were significantly correlated with measurements for all scenarios. The maximum total error achieved between simulations and measurements was 2.6%, suggesting that predictions are accurate to within 3% of the average measurement. A low relative bias was observed in the simulations when compared to measured values, suggesting only a small systematic underestimate (≤ 0.5% of average measurement) for most severance operations and a small overestimate (0.14%) for open water blasts.

In graduate programs such as social work, field education is the signature pedagogy of education. As such, student placement with an appropriate field education agency is critical to ensure academic success and career readiness. A variety of Learning Management System (LMS) and Integrated Planning and Advising Service (IPAS) technologies have been developed to fully integrate technology into the educational system and streamline and improve the learning experience for students, educators, and administrators. Few (if any) of the existing solutions have capabilities to match students with field educators on the basis of an individual student’s completed coursework and area of specialization, as well as field educator needs and opportunities. This paper describes our experience developing a custom LMS/IPAS system—the School of Social Work information System (SSWiS)—that was designed specifically for student learning, faculty advising, and academic administration within our social work graduate program. We present the challenges that motivated the design of the SSWiS before describing the architecture and functionality of our solution. We then discuss our preliminary evaluation results. We conclude with a discussion of the benefits and limitations of our system in the context of today’s technical needs in graduate education in social work and other fields.

A simple underwater noise model suitable for use with explosives in the decommissioning of oil and gas subsea structures is introduced and evaluated against data from five projects in the US. The performance of the model is compared to four existing models for open water blasts, and for the severance of well conductors and piles. Simulated received underwater sound pressure levels were significantly correlated with measurements for all scenarios. The maximum total error achieved between simulations and measurements was 3.5%, suggesting that predictions are accurate to within 4% of the average measurement. A low relative bias was observed in the simulations when compared to measured values, suggesting only a small systematic underestimate (≤ 1% of average measurement) for most severance operations and a small overestimate (1.34%) for open water blasts.

Balsam fir trees are a specialty agricultural species that are largely used as Christmas trees. Soil or tissue sampling is seldom performed to assess balsam fir nutrition needs, which can contribute to over or under fertilization and subsequent environmental challenges. Remote sensing to determine the normalized difference vegetation index (NDVI) has had strong relationships with nutrition in other plants. This research aimed to determine whether there is a relationship between NDVI and nutrition in balsam fir. A random sample of 45 trees was selected in autumn of 2021 and then another 70 trees selected in spring of 2022. Soil and needle tissue samples were analyzed for N, P, K, Ca, Mg, S, Fe, Zn, Mn, B, and Cu. An uncrewed aerial vehicle equipped with a multispectral camera was flown over the orchard to determine the NDVI for each tree. Nutrition and NDVI were analyzed for correlations through all sampled trees. Separate correlation analyses were repeated for mature trees (greater than 5 years old) and young trees (less than 5 years old). Soil nutrients N, P, K had a significant relationship with NDVI in autumn sampling. Only N was correlated consistently in both autumn and spring, with R2 of 37% and 33% respectively. Relationships were much stronger when only mature trees were considered, increasing to 60% and 51% respectively. NDVI was found to offer predictive power for tissue N that can be useful to producers to help optimize fertilizer input. However, further work is needed to refine these relationships.

Under the same seismic load, different local topography will have different effects, which is an important research field in seismic engineering. Hills are connected with valleys is a very typical terrain. Taking this terrain as an example, its response to the most destructive SH waves in the earthquake is studied. By simplifying and dividing the model, the wave functions satisfying the wave equation and boundary conditions in each region are constructed by using the complex function and moving coordinate method. The equations satisfying the boundary continuity conditions are established. With the help of calculation software, the numerical results are obtained. The influence of different parameters on ground motion is discussed.

Workloads may be classified as either internal or external. Internal workloads (heart rate, blood lactate, session rate of perceived exertion (sRPE) are categorised as the individual’s response to an external workload (volume, intensity). sRPE is an easily monitored variable which has been shown to have possible associations with other internal (1) and injury rates (2, 3) in contact sports. This case study describes the internal workload monitoring of a schoolboy rugby player during the entirety of his season (September to March) with the subsequent relationships between workload and time loss injuries being explored. Time loss injuries are defined as injuries which caused the individual to miss training or match play time (4). Acute to chronic workload ratio (ACWR) and exponentially weighted moving average (EWMA) were monitored, a novel ACWR:EWMA ratio was also calculated. High ACWR and low EWMA values were associated with injury occurrence, the ACWR:EWMA ratio may account for this. EWMA may be a better predictor of “time loss” injuries than ACWR. The ACWR:EWMA ratio may merit further scientific exploration in the future.

The objective of this study was to compare the pathogens and susceptibilities of the current automated rule-based technology (RBT) antibiogram with one manually collected through chart review with additional rules applied. This study was a 2-year, retrospective cohort study and included all bacterial cultures within the first 30 days from patients admitted to a single Burn Center. The current RBT antibiogram served as the control and new antibiogram versions were created using additional rules and compared to the control. Six-hundred fifty-seven patients were admitted (61% excluded for lack of cultures). Fifty-nine percent had at least one hospital acquired risk factor with over one-third having recent illicit drug use and one-third having a recent hospitalization. Of the 410 cultures included, 57% were Gram-negative and half were from wound infections. Sensitivities were significantly different when comparing manual and the RBT version after including factors, such as days since admission, presence of hospital acquired risk factors, or previous antibiotic courses. Recommended empiric Gram-negative antibiotics changed from double coverage to a single β-lactam with > 90% susceptibility. The susceptibilities between first and subsequent courses were dramatically different. Before developing an antibiogram or interpreting the output, it is important to consider which automated criteria are utilized, especially for units with extended lengths of stay.

Dementia, primarily caused by neurodegenerative diseases like Alzheimer’s disease (AD), affects millions worldwide, making detection and monitoring crucial. To enable these tasks, we propose encoding in-text pauses and filler words (i.e., “uh” and “um”) in text-based language models, and thoroughly evaluate their effect in performance. Additionally, we suggest using contrastive learning to improve performance in a multi-task framework. Our results demonstrated the effectiveness of our approaches in enhancing the model’s performance, achieving 87% accuracy and an 86% F1-score. Compared to the state-of-the-art, our approach has similar performance despite having significantly fewer parameters. This highlights the importance of pause and filler word encoding on the detection of dementia.

Branching patterns are ubiquitous in nature, consequently over the years many researchers have tried to characterize the complexity of their structures. Due to their hierarchical nature and resemblance to fractal trees, they are often thought to have fractal properties, however their non-homogeneity (i.e., lack of strict self-similarity) is often ignored. In this paper we review and examine the use of the box-counting and sandbox methods to estimate the fractal dimensions of branching structures. We highlight the fact that these methods rely on an assumption of self-similarity that is not present in branching structures due to their non-homogeneous nature. Looking at the local slopes of the log-log plots used by these methods reveals the problems caused by the non-homogeneity. Finally, we examine the role of the canopies (endpoints or limit points) of branching structures in the estimation of their fractal dimensions.

Hill stream loaches are a group of fish that inhabit fast flowing shallow freshwater. The family has radiated over Asia. For some species their range is limited to single catchments; they provide an excellent example of biogeographical speciation on multiple scales. Hill stream loaches have a range of adaptations which help them exploit environments where competitors and predators would be washed away. They have streamlined bodies and keeled scales reminiscent of Mako sharks and potentially many other as yet undiscovered drag reducing features. They adhere to rocks, crawl over shallow films of water, glide over hard surfaces using ground effects and launch into currents to attack prey or evade predation. They offer a test of modern approaches to organismal biology and a broad range of biomimetic potential. In this paper we analyse what behaviour is associated with their physical adaptations and how this might relate to their evolution and radiation. Our intent here is to review information that is presently available but also to derive new insight through combination and statistical analysis of existing material. We also use our own observations and critically argue several contradictory, or poorly supported assertions in the existing scientific literature. Our conclusion is that, although extensively studied, there remain major gaps in knowledge about their organismal biology. We summarise the research opportunities in the form of hypotheses that are worth testing.

In response to a perceived epidemic of coronary heart disease, Ancel Keys introduced the lipid-heart hypothesis in 1953 which asserted that high intakes of total fat, saturated fat, and cholesterol lead to atherosclerosis and that consuming less fat and cholesterol, and replacing saturated fat with polyunsaturated fat, would reduce serum cholesterol and consequently the risk of heart disease. Keys proposed an equation that would predict the concentration of serum cholesterol (DChol.) from consumption of saturated fat (DS), polyunsaturated fat (DP), and cholesterol (DZ): ΔChol. = 1.2(2ΔS − ΔP) + 1.5ΔZ. However, the Keys equation conflated natural saturated fat and industrial trans-fat into a single parameter and considered only linoleic acid as the polyunsaturated fat. This ignored the widespread consumption of trans-fat and its effects on serum cholesterol and promoted an imbalance of omega-6 to omega-3 fatty acids in the diet. Numerous observational, epidemiological, interventional, and autopsy studies have failed to validate the Keys equation and the lipid-heart hypothesis. Nevertheless, these have been the cornerstone of national and international dietary guidelines which have focused disproportionately on heart disease and much less so on cancer and metabolic disorders, which have steadily increased since the adoption of this hypothesis.

Though Bangladesh is often labelled as "climate change ground zero," the Chittagong Hill Tracts (CHT) were never considered a significant climate change hotspot until heavy rainfall and consequent landslides in 2017. This shift in problem narrative seemingly overlooks myriad environmentally unsustainable 'development' initiatives along with (il)legal deforestation. This paper examines climate change trends and impacts on the lives and livelihoods of diverse local groups in CHT. By analysing changing patterns in meteorological data and qualitative information on changes and challenges in everyday life and the livelihoods of local people, we show a shortfall of captured climate data on CHT to make a strong case for climate change. Yet, this study finds that this region is exposed to a substantial threat of land degradation, flash floods, water scarcity, landslides, and other slow and quick onsets due to a combined effect of deforestation, neoliberalised development, and slight changes in temperature and precipitation patterns. This paper calls for proactive measures to address climate change impacts by endorsing sustainable development strategies prioritizing environmental stewardship, social justice, and economic prosperity.

How a species is represented by marketers of animal-based products both reflects and shapes how consumers think about that animal. By examining the explicit statements, and implicit messages encoded in the imagery on supermarket egg boxes, this paper explores how hens are represented by whole egg retailers. Content analysis reveals two prominent messages purveyed through eggbox graphics, namely those pertaining to hen welfare and human health. The later disenfranchises hens from their products by focusing on the nutritional value of eggs, whereas the former reflects a public concern for the welfare of egg-laying hens. Although claims of improvements in welfare practices are undoubtedly exploited as marketing tools, they serve to raise awareness and drive competitors to adopt similar practices. Welfare claims are a direct response to public concerns about the plight of hens, and may positively influence industry welfare standards. However, idyllic depictions displayed on eggboxes also lull consumers into the belief that those eggs are an ethically sound food choice, regardless of the actual standard of living experienced by the hens.

Animal-based measures are the measure of choice in animal welfare assessment protocols as they can often be applied completely independently to the housing or production system employed. Although there has been a small body of work on potential animal-based measures for farmed crocodilians [1-3], they have not been studied in the context of an animal welfare assessment protocol. Potential animal-based measures, that could be used to reflect the welfare state of farmed crocodilians, were identified and aligned with the Welfare Quality® principles of good housing, good health, good feeding and appropriate behaviour. A consultation process with a panel of experts was used to evaluate and score the potential measures in terms of validity and feasibility. This resulted in a toolbox of measures being identified for further development and integration into animal welfare assessment on the farm. Animal-based measures related to ‘good feeding’ and ‘good health’ received the highest scores for validity and feasibility by the experts. There was less agreement on the animal-based measures that could be used to reflect ‘appropriate behaviour’. Where no animal-based measures were deemed to reliably reflect a welfare criterion nor be useful as a measure on the farm, additional measures of resources or management were suggested as alternatives. Future work in this area should focus on the reliability of the proposed measures and involve further evaluation of their validity and feasibility as they relate to different species of crocodilian and farming system.

While obesity is recognized as a key global public health issue, there has been no research to date on the perceptions of care for people with this condition held by individuals in positions of organizational power. The aim of this study was therefore to describe the perceptions and experiences of clinical leaders and managers of providing care to inpatients with obesity at a metropolitan public health service. This study applied an interpretative phenomenological analysis (IPA) approach to qualitative research, conducting interviews with 17 participants. Their perceptions of care for inpatients with obesity encompassed both their personal understanding as an individual, and their observations about the organizational, patient and carer perspectives. Three overall themes were identified: 1) The problem of inpatients with obesity, 2) Inpatients with obesity as sources of risk and 3) Personal and professional perceptions of inpatients with obesity. While clinical leaders and managers were aware of potential impact of stigma and weight bias on the care given to this cohort, elements of implicit bias, stereotyping, ‘othering’ and ambivalence were frequently present in the data. Ongoing efforts to improve care for patients with obesity must therefore include efforts to address perceptions and attitudes at all organisational levels of the workforce.

Large ruminant production in developing countries is inefficient with low growth rates and likely high greenhouse gas emissions (GHGe) per unit of meat or milk produced. Trials conducted in Lao PDR from 2017-2020, studied ad-libitum supplementation for 12 weeks with 20kg high quality molasses nutrient blocks (MNB; Four Seasons Pty Ltd, Brisbane, Australia), that were either: non-medicated (NMB); fenbendazole-medicated (FMB5, Panacur100®, Coopers Australia, @ 5g/kg); triclabendazole-medicated (TMB5 or TMB10, Fasinex®, Novartis Australia, @ 5g/kg or @ 10g/kg, respectively); or formulated with urea (UMB8 or UMB10 @ 8% or 10% urea, respectively). Average daily gains (ADG) were determined for access to all MNB’s and compared with access to NMB’s, no supplementation, or previously determined free-grazing baseline ADG’s (55–84g in cattle; 92–106g in buffalo). ADGs were significantly improved following access to all MNBs for periods up to 12wks. ADGs following access to UMB8 or NMB were calculated for three age cohorts of cattle: young calves <8m (238-298g), growing cattle (143-214g) and lactating cows (179-191g). Modelling using IPCC Inventory software model V 2.69 of published data demonstrated a conservative net abatement of 350kg CO2e was achievable over a 200 day feeding period. An additional trial of Emissions control blocks (EMB’s, n = 200) distributed to farmers (n = 60) and two educational institutions, was conducted. Consumption rates (156g/day) and farmer and institutional acceptance of EMB’s were similar to published findings with other MNB’s, confirming all MNB’s and EMB’s improved animal productivity and body condition score, with healthier animals that were easier to manage. Modelling of changes in GHGe intensity identified an abatement of 470kg CO2e per EMB consumed, delivering a total project emissions abatement of 94t CO2e. Provision of MNBs and EMBs in smallholder large ruminant production systems is likely to achieve impressive abatement of GHGe due to improved efficiency of rumen fermentation and productivity.

Chikungunya virus (CHIKV) is a mosquito borne RNA virus that poses an emerging threat to humans. As other RNA viruses, CHIKV encodes an error-prone RNA polymerase which, in addition to full-length genomes, gives rise to truncated, non-functional genomes coined defective viral genomes (DVGs). DVGs have been intensively studied in the context of therapy, as they can inhibit viral replication and dissemination in their hosts. In this work, we interrogate the influence of viral RNA secondary structures on the production of CHIKV DVGs. We experimentally map RNA secondary structures of CHIKV genome using selective 2′-hydroxyl acylation analyzed by primer extension and mutational profiling (SHAPE-MaP), which couples chemical labelling with next-generation sequencing. We correlate the inferred secondary structure with preferred deletion sites of CHIKV DVGs. We document an increased probability of DVG generation with truncations at unpaired nucleotides within the secondary structure. We then generated a CHIKV mutant bearing synonymous changes at the nucleotide level to disrupt existing RNA secondary structure (CHIKV-D2S). We show that CHIKV-D2S presents altered DVG generation compared to wild-type virus, correlating with its change in RNA secondary structure obtained by SHAPE-MaP. Our work thus demonstrates that RNA secondary structure impacts CHIKV DVG production during replication.

Modern radio spectrometers make measurement of polarized intensity as a function of Faraday depth possible. I investigate the effect of depolarization along a model line of sight. I model sightlines with two components informed by observations: a diffuse interstellar medium with a lognormal electron density distribution and a narrow, denser component simulating a spiral arm or H~{\sc ii} region, all with synchrotron-emitting gas mixed in. I then calculate the polarized intensity from 300-1800 MHz and calculate the resulting Faraday depth spectrum. The idealized synthetic observations show far more Faraday complexity than is observed in Global Magneto-Ionic Medium Survey observations. In a model with a very nearby H~{\sc ii} region observed at low frequencies, most of the effects of a ``depolarization wall'' are evident: the H~{\sc ii} region depolarizes background emission and less (but not zero) information from beyond the H~{\sc ii} region reaches the observer. In other cases, the effects are not so clear, as significant amounts of information reach the observer even through significant depolarization, and it is not clear that low-frequency observations sample largely different volumes of the interstellar medium than high-frequency observations. The observed Faraday depth can be randomized such that it does not always have any correlation with the true Faraday depth.

Docking the tail of lambs is a standard husbandry procedure and is achieved through several techniques including clamps, hot or cold knives and latex rings, the last of which is the most popular. All tail docking methods cause acute pain which can be reduced by application of local anesthetic, however precise anatomical injection for optimal efficacy requires considerable skill. This pen trial evaluated the ability of local anesthetic delivered with a dual function ring applicator / injector to alleviate acute tail docking pain. Thirty ewe lambs were assigned to one of three treatment groups (n = 10 per group): ring plus local anesthetic (Ring LA), ring only (Ring) and sham handled control (Sham). Lambs were videoed and behavior categorized every 5 minutes for the first hour and every 10 min for the subsequent 2 hours after treatment. There was a significant effect (p &lt; 0.001) of treatment on total active pain related behaviors in the first hour, with Ring lambs showing higher counts compared to Ring LA or Sham. Ring lambs also displayed a significantly higher count of combined abnormal postures (p &lt; 0.001) than Ring LA or Sham lambs. Delivery of 1.5ml of 2% lignocaine via the dual action device abolished abnormal behaviors and signs of pain in Ring LA lambs. However, lambs in the Ring LA group spent less time attempting to suckle compared to Ring and Sham lambs, suggesting that some residual discomfort remained.

Nutrient profiling (NP) models that assess nutrient density of foods can help remedy micronutrient deficiencies. We used NP methods to identify the most nutrient-rich foods in the 2019 FAO/INFOODS Western Africa Food Composition Table (WAFCT). The WAFCT had complete data for 909 foods. Three versions of the well-established Nutrient Rich Food (NRF) model were used: 1) the original NRF9.3; 2) a new NRF6.3 based on 6 priority micronutrients (iron, zinc, calcium, folate, vitamin A, vitamin B12); and 3) NRF 15.3, based on 15 nutrients to encourage (NRF6.3 nutrients + vitamin D, vitamin E, vitamin C, vitamin B1, vitamin B2, vitamin B3, vitamin B6, copper, and magnesium). Data analyses used one-way ANOVAs and independent t-tests, with significance at α=0.05. Animal-source foods were rated higher by NRF6.3 priority micronutrient and NRF15.3 NP models than by the NRF9.3 model. African indigenous vegetables had higher protein content and higher nutrient density compared to non-indigenous vegetables. African indigenous grains had higher nutrient density compared to non-indigenous grains. Though animal-source foods received some of the highest scores, NP models adapted to the West African context showed that African indigenous vegetables and grains were also nutrient rich. Indigenous foods could be important sources of priority micronutrients for the region.

Over the last 15 years, the advent of high-throughput ‘omics’ techniques has revealed the multiple roles and interactions occurring among hosts, their microbial partners and their environment. This microbiome revolution has radically changed our views of biology, evolution and individuality. Sitting at the interface between a host and its environment, the microbiome is a relevant yet understudied compartment for ecotoxicology research. Various recent works confirm that the microbiome reacts to and interacts with contaminants, with consequences for hosts and ecosystems. In this paper, we thus advocate for the development of a “microbiome-aware ecotoxicology” of organisms. We emphasize its relevance and discuss important conceptual and technical pitfalls associated with study design and interpretation. We identify topics such as functionality, quantification, temporality, resilience, interactions and prediction as major challenges and promising venues for microbiome research applied to ecotoxicology.

In an increasingly complex world there is a real, urgent need for methodologies to enable engineers to model complex sociotechnical systems, as these now seem to describe the majority of systems in use today. This is of course exacerbated by the increasing involvement and augmentation with “black box” AI contributions. Hollnagel produced a methodology, (FRAM) which did allow the analyst in-sights into these systems’ behaviour, but the model-based system engineering applications demand numbers and a quantitative ap-proach. In the last 10 years, this original approach developed to model systems as sets of interactive, interdependent “functions”, (abstracted from agent or component details), has been further developed to the point where it can take the basic data and structures from the current component focussed system engineering “models”, and can pull it all together into dynamic models, (as opposed to static, fixed System Theoretic Process Accimaps), from which analysts can discern how they really work in practice, and predict the emergent behaviours characteristic of complex systems. This paper describes how the FRAM methodology has now been extended to provide these extra, essential attributes. It also describes its implementation using an open-source software, freely available for use and verification on the GitHub site.

In his Cynefin classification of system behaviours, Snowden (2007), posits that his Simple (Clear ) and even Complicated system categories are sufficiently understandable to be amenable to the traditional methods of system analysis and modelling. Here, relationships between entities in the system are clear and unambiguous and they behave predictably. So, we can build mathematical “models” to describe how the system is expected to function in different situations. Leaving aside his fourth category, Chaotic, as too hard for the moment, this paper focusses on the third category, Complex systems. Yaneer Bar-Yam [1998] defined "complex systems" as systems that "have multiple interacting components, whose collective behaviour cannot be simply inferred from the behaviour of components." So, the traditional system modelling approach of decomposition into components and attempting to build up a picture of system performance from individual pieces, alone, is no longer appropriate for this class. The problem is that most of the methods we currently employ, and particularly the methods that attempt to make the case that these systems are safe, (such as Fault trees, FMEA. and Root Cause Analysis), rely on this decomposition into components and attempt to make the parts more reliable individually. Even the more systemic approaches, such as Reason’s (1990) Swiss Cheese Model, and Leveson’s System Theoretic Analysis (STPA) (2004), encourage adding layers of protection, barriers, strengthened control loops and better safety critical systems, in the hope that they are making the systems safer. But without a valid model to test the effectiveness of these add-ons, we cannot be sure that they will not have an opposite effect, of making the systems even more complex, unreliable and unpredictable. For complex systems, the careful gathering and documentation of system components and their relationships is still a necessary first step, but we need an additional capacity to model these complex systems to test out and prove they work safely and successfully in the real world. (not just draw fixed component relationships as system “models” (wiring diagrams)) In the last 10 years, an original approach developed by Hollnagel, (2012), to model systems as sets of interactive, interdependent “functions”, (abstracted from and independent of component details), has now been developed to the point where it can take the basic data and structures from the current component focussed system engineering “models”, such as MBSE( Goldberg (1994)), and can pull it all together in a dynamic system model from which analysts can discern how it really works in practice, and predict the emergent behaviours characteristic of complex systems. The paper describes how this methodology developed and how it is currently used to model real situations, to analyse incidents and anticipate events.

This review examines the challenges faced by the pig industry, with a specific emphasis on improving the health and growth of weaned pigs. It emphasises the immediate necessity of investigating alternative approaches to managing pig nutrition and health due to restrictions on the use of antibiotics and the prohibition of zinc oxide in weaned pig diets. The weaning phase is identified as a critical stage in piglet development, characterized by stressors that affect their gastrointestinal health, immune responses, and overall physiology. The primary challenge during weaning arises from transitioning piglets from a digestible milk-based diet to a less digestible cereal-based feed, causing nutritional stress. This manifests as reduced feed intake, leading to gastrointestinal disturbances, intestinal inflammation, and adverse effects on intestinal structure and microbiota. To address these challenges and optimise piglet development, various nutritional strategies have been explored. Notably, glucans, particularly β-glucans from fungi, cereals, algae, and yeast, show promise in alleviating weaning-related issues. Furthermore, it's important to highlight the critical roles played by vitamin D and selenium in piglet nutrition. These essential nutrients can be sourced naturally from enriched mushrooms that are specifically enriched with vitamin D and selenium, providing a valuable dietary option. In conclusion, effective nutritional strategies, including glucans, vitamin D, selenium, and enriched mushrooms, are beneficial for addressing weaning-related challenges.

Use of local anesthesia at the time of ring castration and tail docking can improve lamb welfare. However, few local anesthetics are registered for sheep, and data on their duration of effect is limited. Three studies were conducted to evaluate the efficacy of procaine (P), lidocaine (L) and bupivacaine (B) in terms of observed alleviation of behavioral responses to castration and/or tail docking in 10-min blocks in the first 60 min post treatment. In each study, comparisons were made between two groups of lambs castrated and/or tail docked with rubber rings and either receiving the agent using the NUMNUTS® instrument (N) or receiving no anesthetic agent (RR). Acute pain behavior was lower in NL (n = 28) than RRL (n = 15) males in the first 10 min post procedure (P &lt; 0.05); lower in NB (n = 16) than RRB (n = 16) males in periods 10-20 min (0.05 &lt; P &lt; 0.01), 20-30 min (P &lt; 0.05) and 40-50 min (0.05 &lt; P &lt; 0.01); lower in NB (n = 16) than RRB (n = 16) females between 20 and 40 min post-procedure (0.05 &lt; P &lt; 0.01); lower in NP (n = 8) than RRP (n = 7) males in period 10-20 min (0.05 &lt; P &lt; 0.01), and lower in NP (n = 9) than RRP (n = 9) females in periods 0-10 min (0.05 &lt; P &lt; 0.01), and 10-40 min (P &lt; 0.05). Analgesic benefits were modest, and the effects of procaine appear to last longer than lidocaine, while bupivacaine is slower to take effect than either procaine or lidocaine but may provide longer lasting analgesia. The duration of action of local anesthetics is short in sheep, and detailed behavioral evaluations are required in the first hour post procedure to establish efficacy.

Reelin depletion and stress seem to affect similar pathways including GABAergic and glutamatergic signaling and both are implicated in psychiatric disorders in late adolescence/early adulthood. The interaction between reelin depletion and stress, however, remains unclear. To investigate this, male and female heterozygous reelin mice (HRM) and wildtype (WT) controls were treated with the stress hormone, corticosterone (CORT), during late adolescence to simulate chronic stress. Glucocorticoid receptors (GR), N-methyl-D-aspartate receptor (NMDAr) subunits, glutamic acid decarboxylase (GAD67) and parvalbumin (PV) were measured in the hippocampus and the prefrontal cortex (PFC) in adulthood. While no changes were seen in male mice, female HRM showed a significant reduction in GR expression in the dorsal hippocampus. In addition, CORT reduced GR levels as well as GluN2B and GluN2C subunits of NMDAr in the dorsal hippocampus in female mice only. CORT furthermore reduced GluN1 levels in the PFC of female mice. The combined effect of HRM and CORT treatment appeared to be additive in terms of GR expression in the dorsal hippocampus. Female-specific CORT-induced changes were associated with overall higher circulating CORT levels in female compared to male mice. This study shows differential effects of reelin depletion and CORT treatment on GR and NMDAr protein expression in male and female mice, suggesting that females are more susceptible to reelin haploinsufficiency as well as late-adolescent stress. These findings shed more light on female-specific vulnerability to stress and have implications for stress-associated mental illnesses with a female bias including anxiety and major depression.

Antimicrobial use in agriculture has been identified as an area of focus for reducing overall antimicrobial use and improving stewardship. In this paper, we outline the design of a complex antimicrobial stewardship (AMS) intervention aimed at developing a national Veterinary Prescribing Champion programme for Welsh farm animal veterinary practices. We describe the process by which participants were encouraged to design and deliver bespoke individualised AMS activities at practice level by forging participant ‘champion’ identities and Communities of Practice through participatory and educational online activities. We describe the key phases identified as important when designing this complex intervention, namely (i) involving key collaborators in government and industry to stimulate project engagement; (ii) grounding the design in the literature, the results of stakeholder engagement, expert panel input and veterinary clinician feedback to promote contextual relevance and appropriateness; and (iii) taking a theoretical approach to implementing intervention design to foster critical psychological needs for participant motivation and scheme involvement. With recruitment of over 80% of all farm animal practices in Wales to the programme, we also describe demographic data of the participating Welsh Veterinary Prescribing Champions in order to inform recruitment and design of future AMS programmes.

The conventional rolled-up model for carbon nanocones assumes that the cone is constructed from a rolled-up graphene sheet joined seamlessly, which predicts five distinct vertex angles. This model completely ignores any effects due to the changing curvature and all bond lengths and bond angles are assumed to be those for the planar graphene sheet. Clearly curvature effects will become more important closest to the cone vertex, and especially so for the cones with the smaller apex angles. Here we construct carbon nanocones which in the assembled cone are assumed to comprise bond lengths and bond angles which are, as far as possible, equal throughout the structure at the same distance from the conical apex. Predicted bond angles and bond lengths are shown to agree well with those obtained by relaxing the conventional rolled-up model using the LAMMPS software. The major objective here is not simply to model physically realisable carbon nanocones for which numerical procedures are far superior, but rather to produce an improved model that takes into account curvature effects close to the vertex, and from which we may determine an analytical formula which represents an improvement on that for the conventional rolled-up model.

More than 20 lines of independent evidence from clinical observations, studies in laboratory animal models, pharmacokinetic considerations, and numerous temporal and spatial associations previously indicate that numerous genetic and environmental factors leading to inflammation and oxidative stress confer vulnerability to aberrant metabolism of acetaminophen during early development, leading to autism spectrum disorder (ASD). Contrary to this conclusion, multivariate analyses of cohort data adjusting for inflammation-associated factors have tended to show little to no risk of acetaminophen use for neurodevelopment. To resolve this discrepancy, here we use in-silico methods to create an ideal (virtual) population of 120000 individuals in which 50% of all cases of virtual ASD are induced by oxidative stress-associated cofactors and acetaminophen use. We demonstrate that Cox regression analysis of this ideal data set shows little to no risk of acetaminophen use if cofactors which create aberrant metabolism of acetaminophen are adjusted for in the analysis. Further, under-reporting of acetaminophen use is shown to be a considerable problem for this analysis, leading to large and erroneously low calculated risks of acetaminophen use. In addition, we argue that factors which impart susceptibility to acetaminophen-induced injury, and propensity for acetaminophen use itself, can be shared between the prepartum, peripartum, and postpartum periods, creating additional difficulty in analysis of existing datasets to determine risks of acetaminophen exposure for neurodevelopment during a specific time frame. It is concluded that risks of acetaminophen use for neurodevelopment obtained from multivariate analysis of cohort data depend on underlying assumptions in the analyses, and that other evidence, both abundant and robust, demonstrate the critical role of acetaminophen in the etiology of ASD.

Toxicological studies have shown that the cockroach Periplaneta americana is a classical model for studying the mode of action of commonly used insecticides. In a previous study, we demonstrated that thiamethoxam and clothianidin decreased locomotor activity and decreased the locomotor activity in an open-field-like apparatus. Here, we tested the effect of the neonicotinoid acetamiprid when applied orally, topically, or injected into the haemolymph. We found that acetamiprid decreased locomotor activity in the open-field-like apparatus. When treated with acetamiprid, a strong alteration in locomotor activity was observed 1 h, 24 h and 48 h after haemolymph and topical applications. Oral application of acetamiprid demonstrated that it impaired locomotor activity at 24 h and 48 h. A comparison of the present data with our previously published results showed that neonicotinoids were more active when injected into the haemolymph compared to oral and topical applications. These findings increased our understanding of the effect of neonicotinoid insecticides on insect locomotor activity, and demonstrated that the cyano-substituted neonicotinoid, acetamiprid, was able to alter cockroach locomotor activity.

The Human Herpesviruses persist in the form of a latent infection in specialized cell types. During latency, the herpesvirus genomes associate with cellular histone proteins and the viral lytic genes assemble into transcriptionally repressive heterochromatin. Although there is divergence in the nature of heterochromatin on latent herpesvirus genomes, in general the genomes assemble into forms of heterochromatin that can convert to euchromatin to permit gene expression and therefore reactivation. This reversible form of heterochromatin is known as facultative heterochromatin and is most commonly characterized by polycomb silencing. Polycomb silencing is prevalent on the cellular genome and plays a role in developmentally regulated and imprinted genes, as well as X chromosome inactivation. As herpesviruses initially enter the cell in an un-chromatinized state, they provide an optimal system to study how de novo facultative heterochromatin is targeted to regions of DNA and how it contributes to silencing. Here, we describe how polycomb-mediated silencing potentially assembles onto herpesvirus genomes, synergizing what is known about herpesvirus latency with facultative heterochromatin targeting to the cellular genome. A greater understanding of polycomb silencing of herpesviruses will inform on the mechanism of persistence and reactivation of these pathogenic human viruses and provide clues regarding how de novo facultative heterochromatin forms on the cellular genome.

Evaluating the integrity of structures is an important issue in engineering applications. The use of vibration-based techniques has become a common approach to assessing cracks, which are the most often occurring damage in structural elements. When involving an inverse method, it is necessary to know the influence of the position and the geometry of the crack on the modal parameter changes. The geometry of the crack, both in size and shape, defines the damage severity (DS). In this study, we present a method (DS-SHC) used for estimating the DS for closed and open transverse cracks in beam-like structures by using the intact and damaged beam deflections under its weight and a Stochastic Hill Climbing (SHC) algorithm. After describing the procedure of applying DS-SHC, we calculate for a prismatic cantilever beam the severities for different crack types and depths. The results are tested by comparing the DS obtained with DS-SHC with those acquired from dynamic tests made using professional simulation software. We obtained a good fit between the severities determined in these two ways. Afterward, we performed laboratory experiments and find out that the severities obtained with the DS-SHC method can accurately predict the frequency changes due to the crack. Hence, these severities are a valuable tool for damage detection.

Background: Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS), Gulf War Ill-ness (GWI) and control subjects had fMRI during difficult cognitive tests performed before and after submaximal exercise provocation (Washington 2020). Exercise caused increased activation in ME/CFS but decreased activation for GWI in the dorsal midbrain, left Rolandic operculum and right middle insula. Midbrain and isthmus nuclei participate in threat assessment, attention, cognition, mood, pain, sleep, and autonomic dysfunction Methods: Activated midbrain nuclei were inferred by re-analysis of data from 31 control, 36 ME/CFS and 78 GWI subjects using a seed region approach and the Harvard Ascending Arousal Network. Results: Before exercise, control and GWI had greater activation during cognition than ME/CFS in left pedunculotegmental nucleus. Postexercise ME/CFS had greater activation than GWI for midline periaqueductal gray, dorsal and median raphe, and right midbrain reticular formation, parabrachial complex and locus coeruleus. The change between days (delta) was positive for ME/CFS but negative for GWI indicating reciprocal patterns of activation. Controls had no changes. Conclusions: Exercise caused opposite effects with increased activation in ME/CFS but decreased activation in GWI indicating different pathophysiological responses to exertion and mechanisms of disease. Midbrain and isthmus nuclei contribute to postexertional malaise in ME/CFS and GWI.

Although it’s been some forty years since we started to teach combined modified Fault Tree / Event Tree acyclic digraphs, as much simpler Bow Tie diagrams, their popularity seems undimmed; as their pictorial and focussed discussion prompts, fulfil a valuable function in the safe design and operation of hazardous plants and installations. An excellent review of the current state of the art and an authoritative treatise on the terminology and issues involved has been produced as an internationally recognised standard for using the approach. But just as this model has augmented and helped formalise previous pictorial tools, (such as “Dominoes” and holey “Cheese” slices), this paper suggests and sets out to show how we can build on even this current cornerstone of practice and augment its versatility; with the ability to obtain, what engineers rely on, some more quantitative insights from these pictures. “Layers Of Protection Analysis” (LOPA), has already demonstrated a way of pulling together more quantitative predictions from the pictures. This paper would go further and by concentrating on the function not the physicality of a barrier, outlines a methodology that can extend, not just the quantification ability of the LOPA extension, but present a much more holistic view of how the Barriers, as functions, need to work together, interact and interdepend; often in nonlinear, unexpected ways, to give system designers and operators a much clearer view of actual performance predictions.

As our understanding of the thalamocortical system deepens, the questions we face become more complex. Their investigation requires the adoption of novel experimental approaches complemented with increasingly sophisticated computational modeling. In this review, we take stock of current data and knowledge about the circuitry of the somatosensory thalamocortical loop in rodents, discussing common principles across modalities and species whenever appropriate. We review the different levels of organization, including the cells, synapses, neuroanatomy, and network connectivity. We provide a complete overview of this system that should be accessible for newcomers to this field while nevertheless being comprehensive enough to serve as a reference for seasoned neuroscientists and computational modelers studying the thalamocortical system. We further highlight key gaps in data and knowledge that constitute pressing targets for future experimental work. Filling these gaps would provide invaluable information for systematically unveiling how this system supports behavioral and cognitive processes.

Measurements of optical properties have been used for decades to study particle distributions in the ocean. They have been found useful to constrain suspended mass concentration as well as particle-related properties such as size, composition, packing (particle porosity or density) and settling velocity. Optical properties, however, provide measurements that are biased, as certain particles (based on size, composition, shape or packing) contribute to a specific property more than others. Here we study this issue both theoretically as well as by contrasting different optical properties collected simultaneously in a bottom boundary layer, to highlight the utility of such measurements as well as the biases we are likely to encounter using different optical properties to study suspended particles. In particular, we investigate the possibility to infer settling velocity from vertical profiles of optical measurements, finding that the effects of aggregation dynamics can seldom be ignored.

Glucose is the primary energy fuel used by the brain and is transported across the blood-brain barrier (BBB) by the glucose transporter type 1 and 2.[1] A GLUT1 genetic defect is responsible for glucose transporter type 1 deficiency syndrome (GLUT1DS). Patients with GLUT1DS may present with pharmaco-resistant epilepsy, developmental delay, microcephaly, and/or abnormal movements, with tremendous phenotypic variability. Diagnosis is made by the presence of specific clinical features, hypoglycorrhachia and an SLC2A1 gene mutation. Treatment with a ketogenic diet therapy (KDT) is the standard of care as it results in production of ketone bodies which can readily cross the BBB and provide an alternate energy source to the brain in the absence of glucose. KDTs have been shown to reduce seizures and abnormal movements in children diagnosed with GLUT1DS. However, little is known about the impact of KDT on cognitive function, seizures and movement disorders in adults newly diagnosed with GLUT1DS and started on a KDT in adulthood, or the appropriate ketogenic diet therapy to administer. This case report demonstrates the potential benefits of using a modified Atkins diet (MAD), a less restrictive ketogenic diet therapy on cognition, seizure control and motor function in an adult with newly-diagnosed GLUT1SD.

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

Forensic genetic genealogy, a technique leveraging new DNA capabilities and public genetic databases to identify suspects, raises specific considerations in a law enforcement context. Use of this technique requires consideration of its scientific and technical limitations, including the composition of current online datasets, and consideration of its scientific validity. Additionally, forensic genetic genealogy needs to be considered in the relevant legal context to determine the best way in which to make use of its potential to generate investigative leads while minimising its impact on individual privacy. This article presents these issues from an Australian perspective, with the observations and conclusions likely to be applicable to other jurisdictions.

A custom-designed series of unsymmetrical spiroalkanedithiols having tailgroups comprised of a terminally fluorinated chain and a hydrocarbon chain of varying lengths were synthesized and used to prepare self-assembled monolayers (SAMs) on gold substrates. The specific structure of the adsorbates was of the form [CH₃(CH₂)_n][CF₃(CF₂)₇(CH₂)₈]C[CH₂SH]₂, where n = 7, 9, and 12 (designated as F8H10-C10, F8H10-C12, and F8H10-C18, respectively). The influence of the length of the hydrocarbon chain in the bidentate dithiol on the structure and interfacial properties of the monolayer was explored. A structurally analogous partially fluorinated monodentate alkanethiol and the corresponding normal alkanethiols were used to generate appropriate SAMs as reference systems. Ellipsometric thickness measurements showed an unexpectedly low film thickness for the SAMs derived from the bidentate adsorbates, possibly due to disruptions in interchain packing caused by the fluorocarbon chains (i.e., phase-incompatible fluorocarbon-hydrocarbon interactions), ultimately giving rise to loosely packed and disordered films. Analysis by X-ray photoelectron spectroscopy (XPS) were also consistent with a model in which the films were loosely packed; additionally, the XPS spectra confirmed the attachment of the sulfur headgroups of the bidentate adsorbates onto the gold substrates. Studies of the SAMs by polarization modulation-infrared reflection-adsorption spectroscopy (PM-IRRAS) suggested that as the length of the hydrocarbon chain in the adsorbates was extended, a more ordered surface was achieved by reducing the tilt of the fluorocarbon segment. The wettability data indicated that the adsorbates with longer alkyl chains were less wettable than those with shorter alkyl chains, likely due to an increase in interchain van der Waals forces in the former.

NASA mission systems proposals are often compared using an equivalent system mass (ESM) framework wherein all elements of technology to deliver an effect- its components, operations and logistics of delivery- are converted to effective masses since this has a known cost scale in space operations. To date, ESM methods and the tools for system comparison have not considered complexities wherein systems that serve a mission span multiple transit and operations stages, such as would be required to support a crewed mission to Mars, and thus do not account for the different mass equivalency factors operational during each period and the inter-dependencies of the costs across the mission. Further, ESM does not account well for the differential reliabilities of the underlying technologies. Less reliability should incur an equivalent mass cost for technologies that might otherwise provide a mass advantage. We introduce an extensions to ESM to address these limitations and show that it provides a direct method for analyzing, optimizing and comparing different mission systems. We demonstrate our extended ESM (xESM) calculation with crop production technologies -- an aspect of the developing offworld biomanufacturing suite -- since it represents a case with strong coupling among stages of the mission and a relatively high-risk profile.

In this study, the microbiological quality of traditionally made yoghurt from Northern Uganda and Western Kenya were analysed. Six samples of typical traditionally fermented milk were randomly collected from traditional cattle keepers from Karamojong (UG 1) and Acholi (UG 2) in Northern Uganda), and Kalenjin in Western Kenya (KE). Analysis was carried out for microbial quality of the collected samples and was assessed using the conventional methods for total aerobic mesophilic bacteria, total coliform, lactic acid bacteria, Staphylococcus aureus, Listeria monocytogenes, yeasts, and mould counts. The results showed that the pH of the samples was low (2.9- 3.6). The mean aerobic mesophilic bacterial counts were 5.14 x 109 cfu/ml. The mean counts for mesophilic lactobacilli ranged from x 106 to x 108, cfu/ml. The mean thermophilic lactobacilli count ranged from x 107, to x 109, cfu/ml. However, the thermophilic lactococci counts ranged from x 106, to x 109, cfu/ml. On the other hand, the Streptococci counts were between x 106 to x 108 cfu/ml. The mean counts for the non-Sorbitol E. coli was 3.87 x 103 cfu/ml. The results suggest that although the pH of the yoghurt made in the Acholi and Karamojong (Northern Uganda) and in Kalenjin (Kenya) areas was low, the level of bacteria, yeast, and mould counts indicated poor microbiological quality control. This poses public health concerns. Therefore, attention of the appropriate government agencies is needed to ensure that environment of yogurt produced in a traditional setting in most appropriate condition to reduce contamination.

There is growing awareness that “Nature-based Solutions” (NbS) can help to protect us from climate change impacts whilst slowing further warming, supporting biodiversity and securing ecosystem services. However, the potential of NbS to provide the intended benefits has not been rigorously assessed. There are concerns over their reliability and cost-effectiveness compared to engineered alternatives, and their resilience to climate change. Trade-offs can arise if climate mitigation policy encourages NbS with low biodiversity value, such as afforestation with non-native monocultures. This can result in maladaptation, especially in a rapidly changing world where biodiversity-based resilience and multifunctional landscapes are key. Here we highlight the rise of NbS in climate policy—focussing on their potential for climate change adaptation as well as mitigation—and discuss barriers to their evidence-based implementation. We outline the major financial and governance challenges to implementing NbS at scale, highlighting avenues for further research. As climate policy turns increasingly towards greenhouse gas removal approaches such as afforestation, we stress the urgent need for natural and social scientists to engage with policymakers. They must ensure that NbS can achieve their potential to tackle both the climate and biodiversity crisis while also contributing to sustainable development. This will require systemic change in the way we conduct research and run our institutions.

Acute myeloid leukemia (AML) is a hematological cancer with poor outcomes due to a lack of efficacious targeted therapies. The Nuclear Factor of Activated T Cells (NFAT) family of transcription factors is well characterized as a regulator of the cell cycle and differentiation in the myeloid lineage. Recent evidence has demonstrated that NFAT family members may have roles in regulating AML leukemogenesis and resistance to targeted therapy in myeloid leukemias. Furthermore gene expression data from patient samples show that some NFATs are more highly expressed in poorly differentiated AML and after disease relapse, implying that the NFAT family may have roles in specific types of AML. This review outlines the evidence for the role of NFAT in healthy myeloid tissue and explores how NFAT might regulate AML pathogenesis, highlighting the potential to target specific NFAT proteins therapeutically in AML.

The Greater Amanzule Peatland (GAP) in Ghana represents an important ecosystem facing dynamic land cover changes as a result of both natural and anthropogenic factors. This study integrates multispectral and radar remote sensing data from Landsat-7 and -8, L-band SAR, and SRTM to conduct a machine learning-based analysis of these changes from 2010 to 2020 and to predict future scenarios up to 2040. Findings reveal a 12% expansion in peatland cover, equivalent to approximately 6,570 ± 308.59 hectares, despite declines in specific peatland types. Concurrently, anthropogenic land uses have increased, evidenced by an 85% rise in rubber plantations (from 30,530 ± 110.96 hectares to 56,617 ± 220.90 hectares) and a 6% reduction in natural forest cover (5,965 ± 353.72 hectares). Sparse vegetation, including smallholder farms, decreased by 35% from 45,064 ± 163.79 hectares to 29,424 ± 114.81 hectares. Projections for 2030 and 2040 indicate minimal changes based on current trends; however, these do not consider potential impacts from climate change, large-scale development projects, and demographic shifts, necessitating cautious interpretation. The results highlight areas of stability and vulnerability within the GAP and offer critical insights for the development of targeted conservation strategies. Additionally, the methodological framework presented provides a robust approach for accurate and detailed landscape-scale monitoring of tropical peatlands, applicable to other regions facing similar environmental challenges.

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.

In dementia, particularly Alzheimer's Disease (AD), communication challenges are evident, especially in vocabulary and pragmatic aspects. Affected individuals often use vague, non-specific words, and their speech lacks informative nouns and verbs, leading to imprecise communication. However, aspects like sentence structure, phonology, and articulation are believed to remain intact until later stages, though this view is debated in the research community. The rise of Large Language Models (LLMs) has made significant strides in various domains, including sentiment analysis and question-answering. These advancements have been applied to dementia research, with studies using LLMs to analyze textual data. Some research incorporates pauses in text to enhance performance, while others utilize transfer learning techniques. However, limited datasets for dementia detection pose challenges in training LLMs. Our research presents a novel approach to measuring the impact of in-text encoding strategies by embedding special characters within the text to enhance model performance and incorporating sequences and summaries of their frequency. Our best model achieves 0.88 and 0.86 in f1-score and accuracy, respectively, whereas the baseline has 0.42 and 0.56 in f1-score and accuracy.

Large ruminant production is associated with high greenhouse gas emissions (GHGe) intensity, with the highest in southeast Asia being Laos at 102.9 CO2eq/kg meat produced, compared with average global meat emissions intensity of 33 CO2eq/kg. As recent studies in Laos identified emissions control molasses blocks (ECBs) achieved abatement of 470kg CO2eq/20kg block consumed, a study was conducted with a supplement mix with reported methane reducing properties, containing plant tannins and citral extract, salt, molasses and water. Groups of housed dairy buffalo (n=7) and pasture-fed grazing beef cows (n=11) were randomly selected, body condition scores estimated (BCS:1-5) and baseline nasa-oral methane eructation measured daily for 2 weeks. All animals were offered 300-400g/day of the mix for a month, with buffalo accessing abundant fresh cut forages whereas the grazing cows accessing rice straw and pasture declining in quality and quantity due to severe drought. The buffalo consumed all of the mix and retained their BCS of 3, whereas the cattle consumed between 200-300g/day of the mix and their BCS declined from 1.5 to 1.0 during the trial. Analysis of data points (buffalo n=309; cattle n=378) found average methane concentration (AMP) per animal of both cohorts increased over the 2 week baseline period, then declined during the supplementation period by 36% in the buffalo and 18% in cattle cohorts.

Keywords: cranberry, exercise, proteomics, oxylipins, gut microbiome, metabolomics, immunity

This review paper delves into the multifaceted aspects of pineapple cultivation, focusing on morphology studies, harvesting challenges, and mechanization efforts. Pineapple, renowned for its commercial value and unique flavor, holds a prominent position in global agriculture, with India alone producing 19.64 lakh tonnes annually. However, the hilly terrains of regions like northeastern India pose significant hurdles to traditional harvesting methods, necessitating innovative solutions. Understanding the morphology of pineapple plants is crucial for optimizing cultivation practices and designing efficient harvesting equipment. Insights from various studies shed light on leaf structure, fruit maturity, and growth patterns, providing valuable information for engineering tailored solutions. Mechanization endeavors, including semi-mechanized harvesting machines and semi-manual harvesters, demonstrate promising results in improving efficiency and reducing labor-intensive practices. Despite challenges such as increased crop losses and operational costs, continued research and development in mechanization hold the key to sustainable pineapple cultivation. This paper underscores the importance of integrating morphology studies and mechanization efforts to address the unique challenges faced by pineapple farmers, particularly in hilly terrains, and highlights the need for ongoing innovation to ensure the long-term sustainability of pineapple cultivation.

We report here a giant microfossil resembling the conidium of an ascomycete fungus (cf. Alternaria alternata). The specimen is preserved in stromatolitic black chert of the Gunflint Iron Formation (Paleoproterozoic Eon, Orosirian Period, ca. 1.9-2.0 Ga) of southern Ontario, Canada, and the rock that provided the thin section may have been collected by Elso Barghoorn as part of the original discovery of the Gunflint microbiota. The large size of the fossil sets it apart from other, tiny by comparison, Gunflint microfossils. The fossil is 200 microns in length and has cross walls. Individual cells are 30-46 microns in greatest dimension. The apical ‘spore’ is cap-shaped, and has partly separated from the rest of the structure. Cloulicaria gunflintensis gen. nov. sp. nov. may provide early evidence for eukaryotes (fungi) in the fossil record, and may also represent the earliest evidence for asexual reproduction in a eukaryote by means of mitospores.

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

Estrogen decline during menopause is associated with altered metabolism, weight gain and increased risk for cardiometabolic diseases. The gut microbiota also plays a role in the development of cardiometabolic dysfunction and is also subject to changes associated with age-related hormone changes. Phytoestrogens are plant-based estrogen mimics that have gained popularity as dietary supplements for treatment or prevention of menopause-related symptoms. These compounds have the potential to both modulate and to be metabolized by the gut microbiota. Hops (Humulus lupulus L.) contain potent phytoestrogen precursors, which rely on microbial biotransformation in the gut to estrogenic forms. We supplemented ovariectomized (OVX) or sham-operated (SHAM) C57BL/6 mice, with oral estradiol (E2), a flavonoid-rich extract from hops, or a placebo carrier oil to observe effects on adiposity, inflammation, and gut bacteria composition. Hops extract and E2 protected against increased visceral adiposity and liver triglyceride accumulation in OVX animals. Surprisingly, we found no evidence of OVX having a significant impact on the overall gut bacterial community structure. We did find differences in abundance of Akkermansia muciniphila, which was lower with HE treatment relative to the OVX E2 treatment and to placebo in the SHAM group.

Recommender systems as an effective information filtering system can be used to obtain information through the user's explicit or implicit behavior. On the one hand finding items that may be of interest to the user. On the other hand, the recommendation facilitates the interaction between the user and the item to increase the revenue. Recommender systems have been widely used in various fields, such as e-commerce, travel recommendation, online books and movies, social networks, etc, which can satisfy the intrinsic implicit needs of users through personalized services. In recent years, the development of deep learning has further improved the performance of recommendation systems. Although these methods improve the performance of the recommendation system, when the number of users and products increases, the recommendation system may face sparsity and cold start problems, and thus cannot achieve personalized recommendations. Knowledge graphs, which are structured data, have become the choice of many algorithms due to the high quality and wide scale of the data, and therefore many recommendation algorithms combined with knowledge graphs have emerged as a popular new direction in recommendation systems. These algorithms are able to preserve the rich connections between different entities. Moreover, when constructing the features of an entity, the entities that are far away from the central entity can also be utilized. Entities are no longer only directly connected to each other. To address the shortcomings of existing recommendation algorithms, this paper designs the recommendation algorithm GPRE using graph neural networks. GPRE focuses on expressing the user's features. The graph neural network provides GPRE with a strong generalization capability for modeling, which can provide long-range semantics between users and entities, as well as selective entity selection in the auxiliary graph neural network. Explicit semantic links are established between remote and central nodes to reduce the introduction of noise. In this paper, experiments are conducted on real-world datasets and the results are compared with baselines. The experimental results show that GPRE performs well on the experimental dataset.

Background:Peripheral neuropathy (PN) can result in either partial or complete loss of distal sensation resulting in an increased fall risk. Walkasins^® uses a shoe insert to detect the magnitude and direction of sway and sends signals to a leg unit that provides sensory balance cues. The objective of this case report is to describe the long-term influence of the Walkasins^® lower limb sensory neuroprosthesis on balance and gait for an individual with diabetic PN.Case Description:A fifty-one-year-old male with a 3-year history of PN and a 10-year history of type II diabetes mellitus was fitted with Walkasins^® and utilized the shoe inserts 8-10 hours/day for more than 1 year. Although, vibration and tactile thresholds were severely impaired at his 1^st metatarsophalangeal joint and the lateral malleolus bilaterally he could perceive tactile stimuli from the Walkasins^® above the ankles.Outcomes:Following Walkasins^® use, his Activities-specific Balance Confidence Scale (ABC) scores improved from 33% to 80%. His mean Vestibular Activities of Daily Living (VADL) scores decreased from 3.54 to 1. His Functional Gait Assessment (FGA) scores increased from 13/30 to 28/30 and his miniBESTest scores improved from 15/28 to 26/28. Gait speed increased from 0.23 m/sec to 1.5 m/sec. The patient described a decrease in pain and cramping throughout his lower extremities and an increase in function.Discussion:Gait and balance improved with the use of the Walkasins^® and participation in the Neuro Wellness Program. This improvement suggests that the use of sensory substitution devices, such as the Walkasins^®, may replace sensory deficits related to gait and balance dysfunction experienced by patients with PN. Further research is needed to determine if other patients will have a similar response and what the necessary threshold of sensory function is to benefit from use of the Walkasins^®.

Soil-borne oomycetes include devastating plant pathogens that cause substantial losses in the agricultural sector. To better manage this important group of pathogens, it is critical to understand how they respond to common agricultural practices, such as tillage and crop rotation. Here, a long-term field experiment was established using a split-plot design with tillage as the main plot factor (conventional tillage [CT] vs. no till [NT], 2 levels) and rotation as the subplot factor (monocultures of soybean, corn, or wheat, and corn-soybean-wheat rotation, 4 levels). Post-harvest soil oomycete communities were characterized over three consecutive years (2016-2018) by metabarcoding the Internal Transcribed Spacer 1 (ITS1) region. The community contained 292 Amplicon Sequence Variants (ASVs) and was dominated by Globisporangium spp. (85.1% in abundance, 203 ASV) and Pythium spp. (10.4%, 51 ASV). NT decreased diversity and community compositional structure heterogeneity, while crop rotation only affected the community structure under CT. The interaction effects of tillage and rotation on most oomycetes species accentuated the complexity of managing these pathogens. Soil and crop health represented by soybean seedling vitality was lowest in soils under CT cultivating soybean or corn, while grain yield of the three crops responded differently to tillage and crop rotation regimes.

Obtaining a good socket fit is an iterative process dependent on the skill and experience of the prosthetist creating it, and requiring individualisation based on the size and shape. There is no standard measurement system used to aid prosthetic socket creation, despite the severe impacts on physical health and quality of life if one is ill-fitting. Pressure sensors embedded in a prosthetic socket were used to collect data at the socket-residuum interface. To choose an interpolation method, a 2D grid was used, with previously collected walking test pressure data, to simplify the sensor array with a border for extrapolation. Four multivariable interpolation methods were evaluated to create a colour map of the pressure data. Radial Basis Function interpolation was chosen as it produced a clear image with a graduated interpolation between data points and was used to create a colour map across the surface of a 3D prosthetic socket model. For the model to be accessible to clinical audiences, a desktop application was created using PyQt to view the model. The created application allowed for connection to the sensors via Bluetooth, with the pressure data updating the colour map on the 3D model in real-time. The created application shows the potential for a clinical product, however further development informed by feedback from rehabilitation clinicians and prosthesis users is required

Solids in the interstellar medium consist of an intimate mixture of silicate and carbonaceous grains. Because 99% of silicates in meteorites were reprocessed at high temperatures in the inner regions of the Solar Nebula, we propose that similar levels of heating of carbonaceous materials in the oxygen-rich Solar Nebula would have converted nearly all carbon in dust and grain coatings to CO. We discuss catalytic experiments on a variety of grain surfaces that not only produce gas-phase species such as CH4, C2H6, C6H6, C6H5OH or CH3CN, but also produce carbonaceous solids and fibers that would be much more readily incorporated into growing planetesimals. CO and other more volatile products of these surface mediated reactions were likely transported outwards along with chondrule fragments and small Calcium Aluminum Inclusions (CAIs) to enhance the organic content in the outer regions of the nebula where comets formed. Carbonaceous fibers formed on the surfaces of refractory oxides may have significantly improved the aggregation efficiency of chondrules and CAIs. Carbonaceous fibers incorporated into chondritic parent bodies might have served as the carbon source for the generation of more complex organic species during thermal or hydrous metamorphic processes on the evolving asteroid.

Despite a global push in the development and implementation of widespread alternative energy use, significant disparities exist across given nation-states. These disparities, frequently referred to as the local-national gap, reflect both technical and economic factors, as well as the social, political, and ecological gaps between how communities see energy development and national/global policy goals. This dataset is an attempt to bridge the local-national gap regarding solar PV adoption in the state of Georgia (U.S.A.). This dataset is an aggregation of variables from seven different publicly-available sources that was designed to help researchers interested in the context underlying solar adoption on the local scale of governance (e.g. the county level). The SolarView database includes information necessary for informing policymaking activities such as solar installation information, a historical county zip code directory, county-level census data, housing value indexes, renewable energy incentive totals, PV rooftop suitability percentages, and utility rates. As this is a database from multiple sources, incomplete data entries are noted.

Nature-based solutions (NbS) are increasingly recognised for their potential to address both the climate and biodiversity crises. These outcomes are interdependent, and both rely on the capacity of NbS to support and enhance the health of an ecosystem: its biodiversity, the condition of its abiotic and biotic elements, and its capacity to function normally despite environmental change. However, while understanding of ecosystem health outcomes of nature-based interventions for climate change mitigation is growing, the outcomes of those implemented for adaptation remain poorly understood with evidence scattered across multiple disciplines. To address this, we conducted a systematic review of the outcomes of 109 nature-based interventions for climate change adaptation using 33 indicators of ecosystem health across eight broad categories (e.g. diversity, biomass, ecosystem functioning and population dynamics). We showed that 88% of interventions with positive outcomes for climate change adaptation also reported measurable benefits for ecosystem health. We also showed that interventions were associated with a 67% average increase in local species richness. All eight studies that reported benefits in terms of both climate change mitigation and adaptation also supported ecosystem health, leading to a triple win. However, there were also trade-offs, mainly for forest management and creation of novel ecosystems such as monoculture plantations of non-native species. Our review highlights two major limitations of research to date. First, only a limited selection of metrics are used to assess ecosystem health and these rarely include key aspects such as functional diversity and habitat connectivity. Second, taxonomic coverage is poor: 67% of outcomes assessed only plants and 57% did not distinguish between native and non-native species. Future research addressing these issues will allow the design and adaptive management of NbS to support healthy and resilient ecosystems, and thereby enhance their effectiveness for meeting both climate and biodiversity targets.

In this study, a monoethanolamine aerosol growth model was developed to investigate the aerosol growth factor. Interactions among the internal conditions in an absorber were considered in this aerosol model. Additionally, an experiment was conducted to measure aerosol particle size, for collecting in-house validation data. Sucrose was used as the aerosol nuclei instead of sulfuric acid to prevent the corrosion of equipment used in the experiment. Experimental results showed that the outlet aerosol sizes increased to the same size regardless of the sucrose concentrations. The aerosol growth model was validated using the in-house experimental data. The aerosol growth model efficiently predicted the aerosol size. For investigating aerosol growth effects, particle number concentration was determined to be the primary factor affecting aerosol growth and amine emissions. When the particle number concentration increased, the aerosol size decreased, whereas the MEA emission increased.

The study compares three machine learning and deep learning models—Support Vector Regression (SVR), Recurrent Neural Networks (RNN), and Long Short-Term Memory (LSTM)—for predicting market prices using the NGX All-Share Index dataset. The models were evaluated using multiple error metrics, including Mean Absolute Error (MAE), Mean Squared Error (MSE), Root Mean Square Error (RMSE), Mean Percentage Error (MPE), and R-squared. RNN and LSTM were tested with both 30 and 60-day windows, with performance compared to SVR. LSTM delivered better R-squared values, with a 60-day LSTM achieving the best accuracy (R-squared = 0.993) when using a combination of endogenous market data and technical indicators. SVR showed reliable results in certain scenarios but struggled in fold 2 with sudden spike that shows high probability of not capturing the entire underlying NGX pattern in the dataset correctly as witnessed with the high validation loss during the period. Additionally, RNN faced the vanishing gradient problem that limits its long-term performance. Despite challenges, LSTM's ability to handle temporal dependencies, especially with the inclusion of On-Balance Volume, led to significant improvements in prediction accuracy. The use of the Optuna optimization framework further enhanced model training and hyperparameter tuning, contributing to the performance of the LSTM model.

There is no routine approach to identify patients with gynecologic malignancies at high risk for chemotherapy-resistance. Circulating tumor DNA (ctDNA) tumor fraction (TFx) represents a minimally-invasive approach to tumor profiling, with as yet limited data on utility in gynecologic malignancies. The objective was to investigate the use of ctDNA TFx in a cohort of patients with ovarian and endometrial cancer. Plasma samples from patients with biopsy-proven ovarian or endometrial cancer collected between 4/2018 and 4/2020 were subjected to shallow whole genome sequencing with determination of TFx via ichorCNA package. The association of TFx to continuous and categorical baseline clinicopathologic factors and progression-free survival was assessed. 210 plasma samples from 78 patients with gynecologic cancers were analyzed. Mean TFx for ovarian cancer was 5.5% and endometrial cancer 2.4% and there was no significant difference in TFx among histology either for endometrial or ovarian cancers. Grade was associated with significant difference in ‘sentinel’ TFx among ovarian cancers but not endometrial cancers. ctDNA TFx dynamics over time demonstrated rapid clearance of ctDNA in most patients with ovarian cancer, while endometrial cancer had consistently low TFx. ctDNA TFx is feasible in ovarian and endometrial cancers and may be a valuable important tool for prognostication.

Despite the increasing popularity of liquid chromatography-mass spectrometry (LC-MS)-based lipidomics, there is a lack of accepted and validated method for lipid extract quality and quantity assessment prior to LC-MS. Fourier-Transform Infrared Spectroscopy (FTIR) has been reported for quantification of pure lipids, however, the sample complexity and purity complex lipid extract quantification in lipidomics experiments could be impact quantification accuracy. Here, we report comprehensive assessment of the sample matrix on the accuracy of lipid quantification using Attenuated Total Reflectance Fourier-Transform Infrared Spectroscopy (ATR-FTIR). Pure lipids are characterized by CH-and C=O-stretching vibrations on FTIR, with quantitative range of 40–3000 ng and a limit of detection of 12 ng. Sample extraction method and local baseline subtraction during FTIR spectral processing significantly impact lipid quantification by CH-stretching. To facilitate sample quality screening, we developed the Lipid Quality (LiQ) score from a spectral library of common contaminants, using a ratio of peak heights between CH-stretching vibrations maxima and the collective vibrations from amide/amine, CH-stretching minima and sugar moieties. We evaluated LiQ score as a rapid sample quality control method by comparing to total LC-MS intensity of targeted lipidomics of 107 human plasma lipid extracts. Exclusion of poor-quality samples based on LiQ score improved the correlation between FTIR and LC-MS quantification. Finally, the uncertainty of absolute quantification by FTIR was estimated using a 795 ng SPLASH LipidoMix standard to be &lt;10%. In summary, this study identified key parameters for accurate FTIR-based quantification of complex lipid mixture, and developed a rapid workflow requiring only 1 µL of MS-ready sample and &lt; 5 minutes for routine lipidomics sample quality and quantity assessment.

Although urbanization has contributed to improving living conditions, it has had negative impacts on the natural environment in the urbanized areas. Urbanization has changed the urban landscape and resulted in increasing land surface temperature (LST). Thus, studies related to LST in various urban environments have become a popular research topic. However, few LST studies focusing on the mountain landscapes (i.e. hill stations) have been carried out. The primary objective of this study is to investigate changes in the landscape and their impacts on LST intensity (LSTI) in the tropical mountain city of Nuwara Eliya, Sri Lanka. The study utilized annual median temperatures extracted from Landsat data collected from 1996 to 2017 based on the Google Earth Engine (GEE) interface. The fractions of built-up (BL), forest (FL), and agricultural (AL) land were calculated using land use and cover maps based on the urban-rural zone (URZ) analysis. The urban-rural margin was demarcated based on the fraction of BL (<10%) and LSTI was measured using the mean LST difference in the urban-rural zone. In addition, the mixture of land use types was calculated using the AL/FL and BL/FL fraction ratios, and grid-based density analysis. The result shows that the BL in all URZ rapidly developed, while AL decreased during the period 1996 to 2017. There was minimal change in the forest area of the Nuwara Eliya owing to the government forest preservation policies. The fraction of the BL increased from 32.4% in 1996 to 58.7% in 2017 in the city center zone (URZ₁) resulting in increased mean LST by 4.7 °C. Furthermore, the increase of the BL/FL fraction ratio and the decrease of the AL/FL fraction ratio were positively correlated with the mean LST. Grid-based analysis showed an increasing positive relationship between mean LST and density of BL. This indicated that BL density has been a crucial element in increasing LST in the study area. The results of this study will be a useful indicator to introduce improved landscape and urban planning in the future to minimize the negative impact of LST on urban sustainability.

Background: During placental formation, cytotrophoblasts (CTBs) fuse into multinucleate, microvilli-coated syncytiotrophoblasts (STBs), which contact maternal blood, mediating nutrient, metabolite, and gas exchange between mother and fetus, and providing a barrier against fetal infection. Trophoblasts remodel the surrounding extracellular matrix through the secretion of matrix metalloproteinases (MMPs). Maternal obesity and diabetes mellitus can negatively impact fetal development and may impair trophoblast function. We sought to model the impact of metabolic stress on STB function by examining MMP and hormone secretion. Methods: The BeWo CTB cell line was syncytialized to STB-like cells with forskolin. Cell morphology was examined by electron microscopy and immunofluorescence; phenotype was further assessed by ELISA and RT-qPCR. STBs were exposed to a metabolic stress cocktail (MetaC: 30 mM glucose, 10 nM insulin, and 0.1 mM palmitic acid). Results: BeWo syncytialization was demonstrated by increased secretion of HCGβ and progesterone, elevated syncytin gene expression (ERVW-1 and ERVFRD-1), loss of tight junctions, and increased surface microvilli. MetaC suppressed HCGβ and progesterone and altered both MMP-9 and MMP-2. Conclusions: Metabolic stress modeling diabetes and obesity altered BeWo STB hormone and MMP production in vitro. These results compel further study into the potential impact of metabolic stress on trophoblast formation and function.

Androgenetic alopecia, the most common cause of hair loss affecting both men and women, is typically treated using pharmaceutical options such as minoxidil and finasteride. While these medications work for many individuals, they are not suitable options for all. To date, the only non-pharmaceutical option that the United States Food and Drug Administration has cleared as a treatment for androgenetic alopecia is low-level laser therapy (LLLT). Various clinical trials utilizing LLLT devices of various types are available. However, a myriad of other physical treatments for this form of hair loss are reported in the literature. This review evaluated the effectiveness of microneedling, pulsed-electromagnetic field (PEMF) therapy, low-level laser therapy (LLLT), fractional laser therapy, and non-ablative laser therapy for the treatment of androgenetic alopecia (AGA). It also explores the potential of multimodal treatments combining these physical therapies. LLLT has the majority of evidence in the literature as a physical therapy for androgenetic alopecia. However, other physical treatments, such as non-ablative laser treatments, and multimodal approaches, such as PEMF-LLLT, seem to have the potential to be equally or more promising and merit further exploration.

Steroid hormones have diverse roles in pregnancy; some, such as progesterone and its metabolites, help stabilise pregnancy and can very likely influence the stability of pregnancy and the onset of labour. Changes and disorders in steroidogenesis may be involved in several pregnancy pathologies, such as premature delivery, preeclampsia, and intrahepatic cholestasis. To date, only a few studies have performed steroid analysis in multiple pregnancies. However, these studies offered a limited analysis of the steroidome in children and mothers with multiple pregnancies. Our team and a team from the Department of Steroids and Proteofactors of the Institute of Endocrinology in Prague investigated multiple pregnancies regarding the biosynthesis, transport, and effects of steroids. We recruited two groups of patients: pregnant women with multiple pregnancies as the study group and singleton pregnancies as the control group. Blood samples were drawn from the participants and analysed. Information about the mother, foetus, delivery, and newborn was extracted from medical records. The data were then analysed. The gestational age of twin pregnancies during delivery ranged from 35+3 to 39+3 weeks, while it was 38+1 to 41+1 weeks for the controls. Our findings provide answers to questions regarding the steroidome in multiple pregnancies.

Objective. The primary aim of this 6-month randomized, controlled, blinded clinical pilot study was to compare the percent root coverage obtained using an acellular dermal matrix allograft (ADM) and a coronally positioned tunnel (CPT) technique with two different suturing techniques. Materials and Methods. Sixteen patients with at least one Miller Class I or II recession defect ≥ 3 mm were randomly selected to receive a CPT with ADM using either two independent continuous sling sutures to secure the graft and the soft tissue separately (SEP) or a single continuous sling suture to secure both the graft and the soft tissue together (TOG) in the test group. Percent defect coverage, predictability of achieving 100% root coverage, keratinized tissue width, and attachment levels were assessed. Results. Both TOG and SEP suturing techniques achieved a significant amount of defect coverage, 83 vs. 85%, respectively, with no significant differences between groups. The predictability of achieving complete defect coverage was 63% for both groups. All maxillary sites had 100% coverage. There was a statistically significant gain of keratinized tissue for the TOG (1.1 ± 0.9 mm), while the SEP group gained only minimal amount (0.2 ± 0.8 mm). Conclusions. The single sling, for simultaneous suturing of the soft tissue and acellular dermal matrix, worked as well as two sling sutures used separately for the soft tissue and ADM. Suturing time was reduced by about 50% for the single sling group indicating a significant clinical advantage for the patient and surgeon.

A key feature of pulmonary arterial hypertension (PAH) is the hyperplastic proliferation exhibited by the vascular smooth muscle cells from patients (HPASMC). The growth inducers FOXM1 and PLK1 are highly upregulated in these cells. The mechanism by which these two proteins direct aberrant growth in these cells is not clear. Herein we identify cyclin dependent kinase 1 (CDK1) also termed cell division cycle protein 2 (CDC2), as having a primary role in promoting progress of the cell cycle leading to proliferation in HPASMC. HPASMC obtained from PAH patients and pulmonary arteries from Sugen/hypoxia rats were investigated for their expression of CDC2. Protein levels of CDC2 were much higher in PAH than in cells from normal donors. Knocking down FOXM1 or PLK1 protein expression with siRNA or pharmacological inhibitors lowered the cellular expression of CDC2 considerably. However, knockdown of CDC2 with siRNA or inhibiting its activity with RO-3306 did not reduce the protein expression of FOXM1 or PLK1. Expression of CDC2 and FOXM1 reached its maximum at G1/S, while PLK1 reached its maximum at G2/M phase of the cell cycle. The expression of other CDKs such as CDK2, CDK4, CDK6, CDK7 and CDK9 did not change in PAH HPASMC. Moreover, inhibition via Wee1 inhibitor adavosertib or siRNAs targeting Wee1, Myt1, CDC25A, CDC25B, or CDC25C led to dramatic decreases in CDC2 protein expression. Lastly, we found CDC2 expression at the RNA and protein level to be upregulated in pulmonary arteries during disease progression Sugen/hypoxia rats. In sum, our present results illustrate that the increased expression of FOXM1 and PLK1 in PAH leads directly to increased expression of CDC2 resulting in a potentiated growth hyperactivity of PASMC from patients with pulmonary hypertension. Our results further suggest that the regulation of CDC2, or associated regulatory proteins, will prove beneficial in the treatment of this disease.

By 2020, over 100 countries expanded electric and plug-in hybrid electric vehicle (EV/PHEV) technologies, with global sales surpassing 7 million units. Governments are adopting cleaner vehicle technologies due to proven environmental and health implications of internal combustion engine vehicles (ICEVs), evidenced by the recent COP26 meeting. This article proposes an agent-based model of vehicle activity as a tool for quantifying energy consumption by simulating a fleet of EV/PHEVs within an urban street network at various spatio-temporal resolutions. Driver behaviour plays a significant role in fuel consumption, thus, simulating various levels of individual behaviour enhancing heterogeneity should provide more accurate results of potential energy demand in cities. The study found that 1) energy consumption is lowest when speed limit adherence increases (low variance in behaviour) and is highest when acceleration/deceleration patterns vary (high variance in behaviour) and 2) on average, for tested vehicles, EV/PHEVs were £116.33 cheaper to run than ICEVs across all experiment conditions. The difference in the average fuel costs (electricity and petrol) shrinks at the vehicle level as driver behaviour is less varied (more homogeneous). This research should allow policymakers to quantify the demand for energy and subsequent fuel costs in cities.

The river Teign in Devon has come under scrutiny for failing to meet Environmental Quality Standards for ecotoxic metals due to past mining operations. A disused mine known as Bridford Barytes mine, has been found to contribute a significant source of Zn, Cd and Pb to the river. Recently, studies have been focused on the remediation of such mine sites using low-cost treatment methods to help reduce metal loads to the river downstream. Red mud is a waste product from the aluminium industry, the utilization of this resource has proven an attractive low-cost treatment method for adsorbing toxic metals. Adsorption kinetics and capacity experiments reveal metal removal efficiencies of up to 70% within the first 2 hours when red mud is applied in pelletized form. Biochar is another effective adsorbent with the potential to remove >90% Zn using agricultural feedstock. Compliance of the Teign has been investigated by analysing dissolved metal concentrations and bioavailable fractions of Zn to assess if levels are of environmental concern. By applying a Real-World Application Model, this study reveals that compressed pellets and agricultural biochar offer an effective, low-cost option to reducing metal concentrations and thus improving the quality of the river Teign.

Background: Globally, infections are the third leading cause of neonatal mortality. Predominant risk factors for facility-born newborns are poor hygiene practices that span both the facility and home environments. Current improvement interventions focus on only one environment and tar-get limited caregivers, primarily birth attendants and mothers. To inform the design of a hand hygiene behaviour change intervention in rural Cambodia, a formative mixed-methods research study was conducted to investigate the context specific behaviours and determinants of hand-washing among healthcare workers, maternal and non-maternal caregivers along the early new-born care continuum. Methods: Direct observations of hygiene practices of all individuals providing care to 46 newborns across eight facilities and associated communities were completed and hand hygiene compliance assessed in analysis. Semi structured interactive interviews were subsequently conducted with 35 midwives and household members to explore the corresponding cognitive, emotional, and environmental factors influencing the observed key hand hygiene behaviours. Results: Hand hygiene opportunities during newborn care were frequent in both set-tings (n = 1319) and predominantly performed by mothers, fathers and non-parental caregivers. Compliance to hand hygiene protocol across all caregivers, including midwives, was inadequate (0%). Practices were influenced by the lack of accessible physical infrastructure, time, increased workload, low infection risk perception, nurture-related motives, norms and inadequate knowledge. Conclusion: Our findings indicate that an effective intervention in this context should be multi-modal to address the different key behaviour determinants and target a wide range of caregivers.

Abstract: Non-alcoholic fatty liver disease (NAFLD) begins with lipid accumulation within hepatocytes, but the relative contributions of different macronutrients is still unclear. We inves-tigated the impact of fatty acids, glucose and fructose on lipid accumulation in primary human hepatocytes (PHH) and three different hepatoma cell lines: HepG2, Huh7 and McA-RH7777 (McA). Cells were treated for 48 hours with fatty acids (0 or 200μM), glucose (5mM or 11mM) and fructose (0mM, 2mM or 8mM). Lipid accumulation was measured via Nile Red staining. All cell types accumulated lipid in response to fatty acids (P<0.001). PHH and McA, but not HepG2 or Huh7 cells, accumulated more lipid with 11mM glucose plus fatty acids (P=0.004, fatty acid x glucose interaction, for both), but only PHH increased lipid accumulation in response to fructose (P<0.001). Considerable variation was observed between PHH cells from different individuals. Lipid accumulation in PHH was increased by insulin (P=0.003) with inter-individual variability. Similarly, insulin increased lipid accumulation in both HepG2 and McA cells, with a bigger response in McA in the presence of fatty acids (P<0.001 for fatty acid x insulin). McA were more insulin sensitive than either HepG2 or Huh7 cells in terms of AKT phosphorylation (P<0.001 insulin x cell type interaction). Hence glucose and fructose can contribute to the accumulation of lipid in PHH with considerable inter-individual variation, but hepatoma cell lines are not good models of PHH.

The emotion of disgust protects individuals against pathogens, and it has been found that during pregnancy, it is elevated. Physiological mechanisms discussed in relation to these changes include immune markers and progesterone levels. The aim of this study is to assess the association between steroids and disgust in pregnancy. In a sample of 179 pregnant women, we have analyzed blood serum steroid concentrations and measured disgust sensitivity by text-based questionnaires in the first and third trimester. We found positive correlations between disgust sensitivity and the levels of C19 steroids, including testosterone, but also its precursors in the Δ5 pathway (androstenediol, DHEA, and their sulfates) and the Δ4 pathway (androstenedione). Furthermore, positive correlations between disgust sensitivity and 5α/β-reduced C19 steroid metabolites were consistently present in both trimesters. In the first trimester, we found a positive association between disgust sensitivity and 17-hydroxypregnanolone as well as some estrogens. In the third trimester, we have observed positive associations between disgust sensitivity and cortisol as well as immunoprotective Δ5 C19 7α/β-hydroxy-steroids. Our study has thus shown that disgust sensitivity is positively correlated with immunomodulatory steroids, and in the third trimester, steroids may reflect potential maternal anxiety-related symptoms.

Glutamate NMDA receptor (NMDAR) hypofunction has been proposed to underlie schizophrenia symptoms because administration of NMDAR antagonists reproduces behavioral and molecular schizophrenia-like phenotypes in healthy humans and animal models. However, the role of specific NMDAR subunits in these schizophrenia-relevant characteristics is largely unknown. Mounting evidence implicates the GluN2D subunit of NMDAR in some of these symptoms and pathology. Firstly, genetic and post-mortem studies show changes in the GluN2D subunit in people with schizophrenia. Secondly, the psychosis-inducing effects of NMDAR antagonists are blunted in GluN2D-knockout mice, suggesting that the GluN2D subunit mediates NMDAR antagonist-induced psychotomimetic effects. Thirdly, in the mature brain, the GluN2D subunit is relatively enriched in parvalbumin (PV)-containing interneurons, a cell type hypothesized to underlie the cognitive symptoms of schizophrenia. Lastly, the GluN2D subunit is widely and abundantly expressed early in development which could be of importance considering schizophrenia is a disorder that has its origins in early neurodevelopment. The limitations of currently available therapies warrant further research into novel therapeutic targets such as the GluN2D subunit which may help us better understand underlying disease mechanisms and develop novel and more effective treatment options.

OBJECTIVE A quality improvement study to assess catheter-associated urinary tract infection (CAUTI) rate post-implementation of a bladder catheter with integrated active drain line urine clearance and automated intra-abdominal pressure monitoring in a burn intensive care unit (ICU). DESIGN Eight-year retrospective before and after study (2015–2022). SETTING A single American Burn Association verified Burn Center with fourteen inpatient beds. PATIENTS Patients meeting criteria for admission to a Burn Center METHODS Retrospective cohort study following the implementation of a novel urine output monitoring system with integrated drain line and urine clearance. Data from a 48-month (from January 2015-December 2018) historical control (period 1) were compared to data from a 28-month (from January 2020 to April 2022) post-implementation period (period 2). Pre- and post-implementation CAUTI event incidences were compared. Charts were reviewed to characterize the patients. RESULTS A total of 42 CAUTIs in 2243 patients were identified using the National Health and Safety Network (NHSN) definition during the analyzed period. There were 40 CAUTI events in period 1 and two CAUTIs in period 2. The incidence of CAUTI events pre-implementation was 0.030 (mean of 10 CAUTI events per year) compared to 0.002 (mean of 1 CAUTI event per year) post-implementation of an automatic drain line clearing UO monitoring system showing a significant reduction in CAUTI events (P<0.01, risk ratio novel vs. gravity bladder catheter 0.071, 95% confidence interval: 0.017-0.294). CONCLUSIONS CAUTIs were reduced in the period following the implementation of a novel urinary catheter system with an integrated active drain line and urine clearance in burn patients.

The ectoparasitic mite Varroa destructor is the most significant pathological threat to the western honey bee, Apis mellifera, leading to the death of most colonies if left untreated. An alternative approach to chemical treatments is to selectively enhance heritable honey bee traits of resistance or tolerance to the mite through breeding programs, or select for naturally surviving untreated colonies. We conducted a literature review of all studies documenting traits of A. mellifera populations either selectively bred or naturally selected for resistance and tolerance to mite parasitism. This allowed us to conduct an analysis of the diversity, distribution and importance of the traits in different honey bee populations that can survive V. destructor throughout the globe. In a second analysis, we investigated the genetic bases of these different phenotypes by comparing ’omics studies (genomics, transcriptomics, and proteomics) of A. mellifera resistance and tolerance to the parasite. Altogether, this review provides a detailed overview of the current state of the research projects and breeding efforts against the most devastating parasite of A. mellifera. By highlighting the most promising traits of varroa-surviving bees and our current knowledge on their genetic bases, this work will help direct future research efforts and selection programs to control this pest. Additionally, by comparing the diverse populations of honey bees that exhibit the traits, this review highlights the consequences of anthropogenic and natural selection on the interactions between hosts and parasites.

Mutations in the Neuroligin-3 (Nlgn3) gene are implicated in autism spectrum disorder (ASD) and gastrointestinal (GI) dysfunction but cellular Nlgn3 expression in the enteric nervous system remains to be characterised. We combined RNAScope in situ hybridization for Nlgn3 mRNA and immunofluorescence for cholinergic and VIP-expressing submucosal neurons, nitrergic and calretinin-containing myenteric neurons and glial cells. We measured Nlgn3 mRNA neuronal and glial expression via quantitative 3-dimensional image analysis. To validate dual RNAScope/immunofluorescence data, we interrogated available single cell RNA sequencing (scRNASeq) data to assess for Nlgn3, Nlgn1, Nlgn2 and their binding partners, Nrxn1-3, MGDA1 and MGDA2, in enteric neural subsets. Most submucosal and myenteric neurons expressed Nlgn3 mRNA. In contrast to other Nlgns and binding partners, Nlgn3 was strongly expressed in enteric glia, suggesting a role for Neuroligin-3 in mediating enteric neuron-glia interactions. The autism-associated R451C mutation reduces Nlgn3 mRNA expression in cholinergic but not VIPergic submucosal neurons. In the myenteric plexus, Nlgn3 mRNA levels are reduced in calretinin and NOS labelled neurons and S100ß labelled glia. We provide a comprehensive cellular profile for neuroligin-3 expression in ileal neuronal subpopulations of mice expressing the R451C autism-associated mutation in Nlgn3, which may contribute to the understanding of the pathophysiology of GI dysfunction in ASD.

At the Rio Conference in 1992, the sustainable development agenda promised a new era for natural resource management, where the well-being of human society would be enhanced through the sustainable use of natural capital. Several decades on, economic growth continues unabated at the expense of natural capital, as evidenced by biodiversity loss, climate change and further environmental issues. Why is this happening and what can be done about it? In this research, we present three Agent-Based Models that explore the social, economic and governance factors driving (un)sustainability in complex social-ecological systems. Our modelling results reinforce the idea that the current economic system does not protect the natural capital on which it depends. This is due to a disjunction between the economic and environmental elements upon which the sustainable development paradigm is founded. Additionally, various factors appear to enhance social-ecological system unsustainability: the role of financial entities and monetary debt; economic speculation; technological development and efficiency; lack of long-term views and late government interventions; inefficient tipping point management; and the absence of strong top-down and bottom-up conservation forces. Interestingly, alternative scenarios showed that these same factors could be redirected to enhance sustainable development. The current economic system may, therefore, not be inherently unsustainable, but rather specific economic mechanisms, agents’ decision-making, and the kinds of links between economic and natural systems could be at the root of the problem. We argue that short- and medium-term sustainability can be enhanced by implementing mechanisms that shift capitalist forces to support environmental conservation. Long-term sustainability, however, requires further paradigm change: where the economy integrates, and fully accounts for, externalities and recognises the actual value of natural capital.

Community pharmacists are involved in antimicrobial stewardship through self-care advice and delivering medications for uncomplicated infections. Objectives This mixed methods study aimed to identify opportunities to enhance the role of community pharmacists in the management of patients with suspected or confirmed urinary tract infection (UTI). Methods Data collection was through a service user survey (n=51) and pharmacist surveys and semi-structured interviews before (16 interviews, 22 questionnaires) and after (15 interviews, 16 questionnaires) trialling UTI leaflets designed to be shared with patients. Data were analysed inductively using thematic analysis and descriptive tabulation of quantitative data. Results Twenty-five percent (n=13/51) of service users with urinary symptoms sought help from a pharmacist first and 65% (n=33/51) were comfortable discussing their urinary symptoms with a pharmacist in a private space. Community pharmacists were confident as the first professional contact for service users with uncomplicated UTI (n=13/16, 81%), but indicated the lack of a specific patient referral pathway (n=16/16, 100%), the need for additional funding and staff (n=10/16, 62%), and the importance of developing prescription options for pharmacists (5/16, 31%). All community pharmacists reported playing a daily role in controlling antimicrobial resistance by educating service users about viral and bacterial infections and promoting a healthy lifestyle. Enhancing their role will need greater integrated working with general practices and more prescribers based in community pharmacy. Conclusion This study suggests that community pharmacists could play a greater role in the management of uncomplicated UTI. The current reconfiguration of primary care in England with primary care networks and integrated care systems could provide a real opportunity for this collaborative working with potential learning for international initiatives.

The COLOSS research association has been assessing honey bee colony losses, associated risk factors and management, focusing on Western countries but with a progressive international expansion. Here, we report the first survey on the loss rates of colonies in 2022/23 in Ethiopia using COLOSS monitoring survey tools. A face-to-face interview questionnaire survey was conducted on 64 beekeepers selected from Oromia and Tigray regions. This covered 1,713 honey bee colonies distributed in 68 apiaries. The percentages of colonies lost were significantly different between Oromia (24.1%) and Tigray (66.4%) regions. Colony losses were attributed as unsolvable queen problems (8% in Oromia; 10% in Tigray), natural disaster (32%; 82%), and empty hives or dead colonies (60%; 8%). The loss rate was significantly affected by queen replacement (p

Breast cancer is the most prevalent type of disease among women. It has become one of the foremost causes of death among women globally. Early detection plays a significant role in administering personalized treatment and improving patient outcomes. Mammography procedures are often used to detect early-stage cancer cells. This traditional method of mammography while valuable has limitations of potential for false positives and negatives, patient discomfort, and radiation exposure. Therefore, there is a probe for more accurate techniques required in detecting breast cancer, leading to exploring the potential of machine learning in the classification of diagnostic images due to its efficiency and accuracy. This study conducted a comparative analysis of pre-trained CNNs (ResNet50 and VGG16) and Vision Transformers (ViT-Base and SWIN Transformer) with the inclusion of ViT-Base trained from scratch model architectures to effectively classify breast cancer mammographic images into benign and malignant cases. The Swin transformer exhibits superior performance with 99.8% accuracy and a precision of 99.8%. These findings demonstrate the efficiency of deep learning to accurately classify breast cancer mammographic images for the diagnosis of breast cancer, leading to improvement in patient outcomes.

Many drastic actions are taken by cocaine users for the sake of experiencing high dopamine levels, which depends on iron for its synthesis. Dopamine depletion and iron deficiency are also involved in the symptoms of restless leg syndrome (RLS). The intersecting biochemical pathways of cocaine use, iron deficiency, and RLS have not been adequately investigated. This case report reveals the successful treatment of a patient with these conditions. A 63-year-old male with a history of cocaine use disorder, insomnia, and RLS sought emergency care for suicidality. Upon admission, he was also found to be iron-deficient. He revealed that his RLS worsened when he attempted to abstain from cocaine. He also used alcohol to sustain the effects of cocaine when the cost of cocaine was too high. During hospitalization, his mood, cravings, and RLS were resolved with adjunctive iron supplementation as well as 300 mg of Wellbutrin. If iron-deficient, replenishment of adequate dopaminergic receptor density and function via supplementation may play an essential role in the prevention of cocaine use and cessation of cocaine withdrawal. Further research is warranted to validate these findings and understand the implications of iron supplementation in addiction medicine.

The human virome is an area of increasing interest with relation to human health and disease. It has been demonstrated to alter in concert with the bacterial microbiome in early life and was also found to be different in patients with certain diseases such as inflammatory bowel disease. However, all virome analyses are hampered by a lack of annotated representative database sequences, often referred to as the ‘viral dark matter’. Here we provide the first description of the gut DNA virome in elderly individuals (>65 years old) as well as the description of novel bacteriophages not present in current reference databases. Diversity analysis comparing elderly persons from different residence locations (community living vs long term care facilities) did not reveal any difference in their virome diversity profiles despite the reported differences at the bacteriome level. An abundance of Microviridae of the subfamily Gokushovirinae were present in the faeces of elderly individuals. Several novel members of the order Caudovirales were also characterized and annotated. Assignment of host bacteria to detected viral genomes was attempted using a combination of CRISPR spacers, tRNA genes and a probabilistic approach. Further characterization of the viral dark matter is necessary for developing tools and expanding databases to study the human virome. This study focused on the virome of an aging human cohort with the goal of illuminating part of the viral dark matter.

Background: Community pharmacies are well-placed to deliver well-being interventions; however, to date, nothing has been produced specifically for this setting. The aim of this study was to develop a positive psychology intervention suitable for a community pharmacy setting with the goal of increasing the well-being of community members. Methods: Intervention development consisted of three steps: Step 1- identify the evidence-base and well-being model to underpin the basis of the intervention (Version 1); Step 2 - model the intervention and gather user feedback to produce Version 2, and Step 3 - revisit the evidence-base and refine the intervention to produce Version 3. Results: Findings from nine studies (seven RCTs, one cross-sectional, one N-1 design plus user feedback were applied to model a 6-week ‘Prescribing Happiness (P-Hap)’ intervention, underpinned by the PERMA model plus four other components from the positive psychology literature (Three Good Things, Utilising Your Signature Strengths in New Ways, Best Possible Selves and Character Strengths). A PERMA-based diary was designed to be completed 3-days a week as part of the intervention. Conclusions: This work is an important development which will direct the future implementation of interventions to support well-being in this novel setting. The next stage is to gain the perspectives of external stakeholders on the feasibility of delivering the P-Hap for its adoption into community pharmacy services in the future.

Herbivores have evolved several strategies to cope with plant defences. Some herbivores are able to resist toxic compounds, while others can manipulate host immunity. Previously it was found that spider mites collected from non-solanaceous wild host plants consist mostly of individuals that induce tomato defences, but also at low frequencies of individuals that can suppress these defences. Also, it has been shown that mites collected from non-solanaceous plants can adapt to tomato by evolving traits that allow them to suppress defences. Hence, we wanted to know if this trait is also common among mites naturally occurring on tomatoes. Here, we compared three T. urticae populations sampled from tomato at three field sites, and also an outbred population created from them through controlled crosses. We then assessed their fecundity on wild-type (WT) tomato plants and def-1 mutants impaired in inducible JA-defences. We also assessed the magnitude of JA defences they induce in WT plants to discriminate between resistant types (high induction and high performance) and those that can suppress defences (low induction, high performance). We then aligned these data with data on variation in mitochondrial DNA cytochrome oxidase I (COI) and effector 84 (a suppressor of JA-defences in planta), in order to compare genetic diversity patterns among mite lines that induce or suppress defences. We found that suppression is the dominant phenotype in mite strains collected from field-grown tomatoes and that inducers and suppressors predominantly cluster in distinct effector 84 clades. We speculate that effector allelic diversity may be subject to natural selection when these mites colonize a novel host plant, promoting traits to cope with plant resistance, such as defence suppression, which facilitates adaptation.

There has been a great deal of research in the area of using graph engines and graph databases to model network traffic and network attacks, but the novelty of this research lies in visually or graphically representing the Reconnaissance Tactic (TA0043) of the MITRE ATT&amp;CK framework. Using the newly created dataset, UWF-Zeekdata22, based on the MITRE ATT&amp;CK framework, patterns involving network connectivity, connection duration, and data volume were found and loaded into a graph environment. Patterns were also found in the graphed data that match the Reconnaissance as well as other tactics captured by UWF-Zeekdata22. The Star motif was particularly useful in mapping the Reconnaissance tactic. The results of this paper show that graph databases/graph engines can be essential tools for understanding network traffic and trying to detect network intrusions before they happen. Finally, an analysis of the run-time performance of the reduced dataset used to create the graph databases showed that the reduced datasets performed better than the full dataset.

The acquisition of regional, 1 metre resolution LIDAR in the PNG Highlands combined with 3D modelling in MoveTM has revolutionized our understanding of the evolution of the Porgera gold mine and areas of new potential. The new 3D model demonstrates active pull-apart basins along a regional transfer during ongoing fold and thrust deformation. When overlain on regional aeromagnetic data, new potential is revealed. The Porgera gold mine is one of the richest in the world and lies in a wide valley at an elevation of 2800m surrounded by mountains up to 4000m high in the middle of the PNG Highlands. It lies along a major lineament, the Porgera Transfer Zone (PTZ), cutting across the orogen that is associated with a 50 km offset of the ophiolite belt. To the NW of the mine there is an extensive belt of low- to high-grade metasediments that formed in deep water during Jurassic rifting, but were metamorphosed during Eocene subduction to the north. Subduction ceased due to accretion of the Sepik Terrane which caused inversion and mild erosion of the Porgera area. The Late Oligocene onset of wrenching in the Mobile Belt to the north placed that area into extension, emplacing metamorphic core complexes, and led to regional subsidence in the Early Miocene. Collision of the margin with the Melanesian Arc in the Middle Miocene caused Late Miocene to Pliocene orogenesis creating the broad mountain belt that we see today, that is still active, as shown by the 2018 MW 7.5 earthquake. Regional mapping of the area using high resolution LIDAR in association with limited field mapping, analysis of gravity and magnetics data and drilling of 300-500m deep core-holes has allowed development of a detailed 3D structural model. The Porgera valley is constrained laterally by the Eastern Boundary and Western Boundary dextral strike-slip faults that lie along the PTZ cutting across the orogeny. However, whilst the position and nature of the faults is clear, due to bending, fracturing and offset of major synclines and anticlines, the faults do not crop-out as significant through-going features. Rather, the dextral offset of basement is soft-linked to the Tertiary limestones at surface due to intervening thick, ductile Cretaceous shales. Fold and thrust structures are ubiquitous in the Tertiary limestones, but the youngest structural features are large extensional faults, particularly around the Porgera valley. The intrusive underlying the Porgera ore-body was emplaced at 6.0+-0.3 Ma, the time of maximum compression during orogenesis. At this time the Eastern Boundary fault and Western Boundary fault were both active allowing a pull-apart basin to form locally along the PTZ at the south-eastern boundary of the Jurassic metasediments. This enabled emplacement of the intrusive. The gold-bearing fluids from the intrusive and metasediments were brought up through the Mesozoic muds to the contact with the Paleogene carbonates where the Porgera ore body was emplaced.

Undernutrition and micronutrient deficiencies such as anemia are considered significant public health challenges in Bangladesh, which enhancing fish consumption is a well-established food-based intervention to address these. This paper documents the establishment of community-based fish chutney production and reports the impact of its consumption on mid-upper arm circumference (MUAC) and hemoglobin (Hb) levels among targeted 150 pregnant and lactating women (PLW) in rural Bangladesh. A fish chutney was developed using locally available ingredients followed by a series of laboratory tests, including nutrient composition, shelf-life and food safety. A community-based fish chutney production process was designed to: 1) supply locally available ingredients for processing; 2) establish two fish drying sites; 3) initiate a community-based production site, and 4) distribute fish chutney to PLW by six women nutrition field facilitators for one year. Then a pre- and post-intervention study was designed for a selected 150 PLW to receive 30g of fish chutney daily for 12 months. Differences in mean mid-upper arm circumference (MUAC) and hemoglobin (Hb) levels pre- and post-consumption were analyzed using one-way analysis of variance. Consumption of 30g of fish-chutney resulted in significant increases of the mean values of Hb levels and MUAC among the targeted PLW.

The human virome is an area of increasing interest with relation to human health and disease. It has been demonstrated to alter in concert with the bacterial microbiome in early life and was also found to be different in patients with certain diseases such as inflammatory bowel disease. However, all virome analyses are hampered by a lack of annotated representative database sequences, often referred to as the ‘viral dark matter’. Here we provide the first description of the gut DNA virome in elderly individuals (>65 years old) as well as the description of novel bacteriophages not present in current reference databases. Diversity analysis comparing elderly persons from different residence locations (community living vs long term care facilities) did not reveal any difference in their virome diversity profiles despite the reported differences at the bacteriome level. An abundance of Microviridae of the subfamily Gokushovirinae were present in the faeces of elderly individuals. Several novel members of the order Caudovirales were also characterized and annotated. Assignment of host bacteria to detected viral genomes was attempted using a combination of CRISPR spacers, tRNA genes and a probabilistic approach. Further characterization of the viral dark matter is necessary for developing tools and expanding databases to study the human virome. This study focused on the virome of an aging human cohort with the goal of illuminating part of the viral dark matter.

The parasitic mite, Varroa destructor, has shaken the beekeeping and pollination industries since its spread from its native host, the Asian honey bee (Apis cerana), to the naïve European honey bee (A. mellifera) used commercially for pollination and honey production around the globe. Varroa is the greatest threat to honey bee health. Worrying observations include increasing acaricide resistance in the varroa population and sinking economic treatment thresholds, suggesting that the mites or their vectored viruses are becoming more virulent. Highly infested weak colonies facilitate mite dispersal and disease transmission to stronger and healthier colonies. Here, we review recent developments in the biology, pathology and management of varroa, and integrate older knowledge that is less well known.

Root research on field grown crops is hindered by the difficulty of estimating root biomass in soil. Root washing, the current standard method is laborious and expensive. Biochemical methods to quantify root biomass in soil, targeting species-specific DNA, have potential as a more efficient assay. We combined an efficient DNA extraction method, designed specifically to extract DNA from soil, with well-established quantitative PCR methods to estimate the root biomass of twenty-two wheat varieties grown in field trials over two seasons. We also developed an assay for estimating root biomass for black-grass, a common weed of wheat cultivation. Two robust qPCR assays were developed to estimate the quantity of plant root DNA in soil samples, one specific to wheat and barley, and a second specific to black-grass. The DNA qPCR method was comparable, with high correlations, with the results of root washing from soil cores taken from winter wheat field trials. The DNA qPCR assay showed both variety and depth as significant factors in the distribution of root biomass in replicated field trials. The results suggest that these DNA qPCR assays are a useful, high throughput tool for investigating the genetic basis of wheat root biomass distribution in field grown crops, and the impact of black-grass root systems on crop production.

Fucoidan is a brown algae-derived polysaccharide having several biomedical applications. This study simultaneously compares the anticancer activities of crude fucoidans from Fucus vesiculosus and Sargassum filipendula, and effects of low (LMW, 10-50kDa), medium (MMW, 50-100kDa) and high (HMW, >100kDa) molecular weight fractions of S. filipendula fucoidan against osteosarcoma cells. Glucose, fucose and acid levels were lower and sulphation was higher in F. vesiculosus crude fucoidan compared to S. filipendula crude fucoidan. MMW had highest the levels of sugars, acids and sulphation among molecular weight fractions. There was a dose dependent drop in focal adhesion formation and proliferation of cells for all fucoidan-types, but F. vesiculosus fucoidan and HMW had the strongest effects. G1-phase arrest was induced by F. vesiculosus fucoidan, MMW and HMW, however F. vesiculosus fucoidan treatment also caused accumulation in sub G1-phase. Mitochondrial damage occurred for all fucoidan-types, however F. vesiculosus fucoidan led to mitochondrial fragmentation. Annexin V/PI, TUNEL and cytochrome c staining confirmed stress induced apoptosis-like cell death for F. vesiculosus fucoidan but features of stress-induced necrosis-like cell death for S. filipendula fucoidans. There was also variation in penetrability of different fucoidans inside the cell. These differences in anti-cancer activity of fucoidans are applicable for osteosarcoma treatment.

Abstract: Background: Dental fear and uncooperative behavior can hinder dental treatment quality. Pediatric Procedural Sedation and Analgesia (PPSA) is used to facilitate treatment when coping capacity is exceeded. Out-of-hospital PPSA has been associated with more adverse outcomes compared to hospital-based settings. Updated Dutch PPSA guidelines recommending two anesthesiologists and a ventilator during out-of-hospital PPSA have increased costs and raised concerns about the accessibility to specialized high quality dental care for children in the Netherlands. Aim: This study aims to investigate the impact of the updated 2017 guideline on the occurrence rate of adverse events during PPSA, as recorded in the anesthesia complication database of twelve participating Dutch dental clinics, with adjustments made for age, weight, and duration of treatment. Method: Data of 25,872 children treated at 12 dental clinics performing out-of-hospital PPSA between 1997 and 2019 were analyzed. Eligible children were aged 2-18 with ASA classification I and II. A logistic two-level mixed-effects model is used to estimate the updated guideline’s impact on adverse events. Results: In the final model we analyzed the data of 21,759 children in nine dental clinics. The OR of the occurrence rate of an adverse event adjusted for age, weight, and duration of treatment was 0.75 (95% CI 0.64 – 0.89) after the implementation of the updated guideline, compared to before the updated guideline. This outcome was significant with a P=0.001, indicating a protective effect. The average odds per clinic of having an adverse event was 0.04 with a 3.81% chance. Conclusion: Our findings demonstrate a significant reduction in adverse events after the implementation of the updated guideline and highlight the importance of adherence to evidence-based guidelines in improving patient safety and the quality of care provided during pediatric procedural sedation and analgesia in out-of-hospital dental clinics. Our study underlines the necessity of considering the complex underlying mechanisms that play a role in the development and implementation of evidence-based practice and safety initiatives on the occurrence of adverse events.