Evans' Syndrome (ES) is a rare autoimmune disorder characterized by the simultaneous occurrence of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Thrombotic complications in ES patients are uncommon, particularly involving Buerger's Disease (BD). We report a case of a 49-year-old male with ES and a history of diabetes and heavy smoking, presenting with a necrotic wound on his right great toe. Diagnostic evaluations revealed severe stenosis and thrombosis in the lower limb arteries, diagnosed as BD. The patient underwent successful popliteal-tibioperoneal artery bypass surgery and subsequent disarticulation and revision of the distal phalanx, followed by the application of an acellular dermal matrix (ADM) to promote healing. Post-surgery, the patient showed significant improvement in blood flow and complete epithelialization without complications. This case highlights the importance of a multidisciplinary approach in managing complex wounds in ES patients, suggesting potential treatment pathways for future cases involving BD

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.

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.

Pneumonic plague outbreaks are relatively infrequent in modern times but in the early part of the 20th century, they were commonplace including several well-documented epidemics responsible for the deaths of thousands. The transmissibility of this disease seems to be discontinuous since in some outbreaks few transmissions occur, while in others, the progression of the epidemic is explosive. Modern epidemiological studies explain that transmissibility within populations is heterogenous with relatively few subjects likely to be responsible for most transmissions and that ‘super spreading events’, particularly at the start of an outbreak, can lead to a rapid expansion of cases. These findings concur with outbreaks observed in real-world situations. It is often reported that pneumonic plague is rare and not easily transmitted but this view could lead to unnecessary complacency since future risks such as the spontaneous incidence of anti-microbial strains, climate change leading to a disruption of natural cycles within plague foci and use of plague as a bioweapon cannot be discounted. Carers and first responders are vulnerable, particularly in poorer countries where access to medicines may be limited, out-breaks occur in inaccessible areas or where there is a lack of surveillance due to a paucity of funds.

Scrub typhus threatens one billion people in the Asia-Pacific area and cases have emerged outside this region. It is caused by infection with any of the multitude of strains of the bacterium, Orientia tsutsugamushi. A vaccine that affords heterologous protection and a commercially available molecular diagnostic assay are lacking. Herein, we determined that the nucleotide and translated amino acid sequences of outer membrane protein A (OmpA) are highly conserved among 51 O. tsutsugamushi isolates. Molecular modeling revealed the predicted tertiary structure of O. tsutsugamushi OmpA to be very similar to that of the phylogenetically related pathogen, Anaplasma phagocytophilum, including the location of a helix that contains residues functionally essential for A. phagocytophilum infection. PCR primers were developed that amplified ompA DNA from all O. tsutsugamushi strains, but not from negative control bacteria. Using these primers in quantitative real-time PCR enabled sensitive detection and quantitation of O. tsutsugamushi ompA DNA from organs of mice that had been experimentally infected with the Karp or Gilliam strains. The high degree of OmpA conservation among O. tsutsugamushi strains evidences its potential to serve as a molecular diagnostic target and justifies its consideration as a candidate for developing a broadly protective scrub typhus vaccine.

Introduction The climate crisis is essentially a public health crisis. Response is imperative to prevent economic and social crises associated with the growing burden of climate impacts on human health and the health care sector. Green Podiatry Pillars By adopting the three pillars of Exercise, Evidence, and Everyday changes, podiatrists can contribute to more sustainable health and health care. Discussion Educating our patients to use their feet for low carbon active transport, eliminating interventions not supported by evidence, and reducing fossil fuel driven supply chains and energy use, are three impactful measures that all podiatrists, and indeed, all health and medical personnel, need to adopt. The avoidable suffering, enormous and costly use of resources for diabetic foot disease, is a scourge that must realise its preventable potential. It is too late, too costly, too polluting, and too sad, to continue to direct health care and research efforts and budgets, to an expensive modifiable diabetes disease process, potentiated by poor food and physical inactivity. Affected patients require skilled support, to avert such chronic disease processes, often not of their making. Conclusions Healthcare contributes 5 to 8% of green house gases (GHG), and non-communicable diseases (NCD) are increasing, so healthcare must lead on primary health. As citizens and health professionals, we must advocate for better community health, and educate our patients. Future Directions All health and medical personnel need to consider planetary health and sustainable healthcare within their daily work. Healthcare must act to address climate change, and realise benefits for people and planet.

The construction of optimized biological fuel cells requires a cathode which combines the longevity of a microbial catalyst with the power density of an enzymatic catalyst. Laccase secreting fungi were grown directly on the cathode of a biological fuel cell to facilitate the exchange of inactive enzymes with active enzymes with the goal of extending the lifetime of laccase cathodes. Additionally, a functionally graded coating was developed to increase enzyme loading at the cathode. Directly incorporating the laccase producing fungus at the cathode extends the operational lifetime of laccase cathodes while eliminating the need for frequent replenishment of the electrolyte. Additionally, the hybrid microbial-enzymatic cathode addresses the issue of enzyme inactivation by using the natural ability of fungi to exchange inactive laccases at the cathode with active laccases. Finally, enzyme adsorption was increased through the use of a functionally graded coating containing an optimized ratio of titanium dioxide nanoparticles and single walled carbon nanotubes. The hybrid microbial-enzymatic fuel cell combines the higher power density of enzymatic fuel cells with the longevity of microbial fuel cells and demonstrates the feasibility of a self-regenerating fuel cell in which inactive laccases are continuously exchanged with active laccases.

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.

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.

Transparent conductive electrodes (TCEs) are of enormous significance to the emergence of flexible and wearable electronics and continued growth of modern devices. Versatile and tunable TCEs, featuring with not only high optical transmittance but also intriguing features of electrochemical energy-storage capability, remain a significant challenge. Here we develop capacitive active films comprised of graphene-conjugated V2O5@poly (3,4-ethylene dioxythiophene) ternary composite (V2O5@PEDOT/rGO) on silver nanowire coated substrates as solid-state super/pseudocapacitors. The constructed electrodes exhibit improved electrolyte ions interaction with effective graphene layer, achieving high areal capacitance 0.6-1.2 mF.cm−2 with 0.5M LiCl electrolytes at optical transparency >60% with record durability. As demonstrated, the kinetic blocking of PEDOT layer and anchoring capability of graphene upon amphoteric soluble vanadium ions from layered V2O5 nanoribbons/nanobelts contribute synergistically to the unusual electrochemical stability, also shown using scanning electrochemical microscopy (SECM) providing electroactivity sites and ion transportation rates. As-fabricated symmetric solid-state supercapacitors delivered broad potential window >1.4 V under two different electrolyte environments (aqueous LiCl and LiCl/PVA gel) and demonstrated higher power and energy density (0.27 μWh.cm−2) outperforming previously reported devices at <0.1 μWh.cm−2. The electrochemical properties are also discussed in terms of solvation in polymer gel electrolyte ions.

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.

Recent advances in synthetic membranes allow their use in fields as diverse as food and agriculture, biotechnology, industrial wastewater treatment, and potable water production. Among the newly developed technologies, nanofiltration for liquids and more particularly for desalination of seawater or saline aquifers are actively pursued. However, current solid-state membranes performance is limited, which calls for the development of novel formulations for membranes offering both high permeability (ion and water flux) and ion differentiation (selectivity), usually considered antagonist features. We report the development of hybrid nanoporous membranes made of solid-state polymeric carbonate track-etched (PCTE) thin films in which biological ion channels such as Gramicidin A (GA), alpha-hemolysin (α-HL), and outer-membrane protein F (OmpF) aquaporin are confined and graphene oxide (GO) conjugated cobalt ion selective binding peptide motifs (Copep) are adsorbed, referring as bioinspired and biomimetic approaches, respectively. These solid-state nanoporous membranes are attracting widespread attention since they offer scalability, mechanical robustness, selectivity, controlled pore dimension and shape, for water sustainability. The ion permeability, ion diffusion coefficient and selective ion recognition are evaluated via nanofiltration, cell diffusion kinetics, and UV-Visible absorption spectroscopy to gain insights into the role of key performance parameters including effective ion confinement in track-etched pores, rich surface chemistry, and peptide-induced channel for selective ion transport. These findings provide new avenues for artificial ion channels by synergistic combination of eco-friendly material design such as GO enabled by bio-molecular recognition chemistry.

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.

The rapid transmission of COVID-19 in school communities has been a major concern. To ensure that mitigation systems were in place and support was available, a digital intervention to encourage and facilitate infection control behaviours was rapidly adapted and optimised for implementation as a whole school intervention. Using the person-based approach, ‘Germ Defence’ was iteratively adapted, guided by relevant literature, co-production with Patient and Public Involvement representatives, and think aloud interviews with forty-five school students, staff, and parents. Suggested infection control behaviours deemed feasible and acceptable by the majority of participants included handwashing/hand-sanitising and wearing a face covering in certain contexts such as crowded public spaces. Promoting a sense of collective responsibility was reported to increase motivation for the adoption of these behaviours. However, acceptability and willingness to implement recommended behaviours seemed to be influenced by participants’ perceptions of risk. Barriers to the implementation of recommended behaviours in school and at home primarily related to childcare needs and physical space. We conclude that it was possible to rapidly adapt Germ Defence to provide an acceptable resource to help mitigate against infection transmission within and from school settings. Adapted content was considered acceptable, persuasive, and accessible.

We have an unprecedented ability to map the Earth’s surface as deep learning technologies are applied to an abundance of high-frequency Earth observation data. Simple, free, and effective methods are needed to enable a variety of stakeholders to use these tools to improve scientific knowledge and decision making. Here we present a trained U-Net model that can map and delineate ground mounted solar arrays using publicly available Sentinel-2 imagery, and that requires minimal data pre-processing and no feature engineering. By using label overloading and image augmentation during training, the model is robust to temporal and spatial variation in imagery. The trained model achieved a precision and recall of 91.5% each and an intersection over union of 84.3% on independent validation data from two distinct geographies. This generalizability in space and time makes the model useful for repeatedly mapping solar arrays. We use this model to delineate all ground mounted solar arrays in North Carolina and the Chesapeake Bay watershed to illustrate how these methods can be used to quickly and easily produce accurate maps of solar infrastructure.

The Safe Drinking Water Act Amendments of 1996 require community water systems in the United States to send consumers Consumer Confidence Reports (CCRs). CCRs contain information on detected contaminants and required educational information about drinking water. The authors of this study developed a survey to evaluate how utilities track consumer feedback, understanding, and the role of the CCR in shaping consumer perceptions about water quality. Responses from this survey indicate it is common for utilities to indirectly track the effectiveness of their CCRs, but few utilities indicated directly evaluating consumer understanding or the effect of CCRs on consumer perceptions.

Uganda possesses natural rainforests that serve enormous environmental ecosystems and biodiversity services. Moreover, the country is known for its various tropical rainforest hardwoods, birds, and animal species. Over the years, the trend in the natural forest land has declined at an alarming rate; hence need to investigate the possible drivers. The loss of such biodiversity and ecosystems risks desertification and extreme climatic condition. As the world moves towards Zero Deforestation 2030, understanding the determinants of deforestation and forest degradation is paramount. Therefore, the main objective of this study was to understand the impact and relationships between net forest conversion, energy emission, agriculture, and forest production of Roundwood. We used data from FAO for the period 2004-2016. Using the ADF and KPSS test, we checked for the unit root presence in the variables. Also, the study used two different regression models: multiple linear regression and dynamic linear model. To analyze the determinants of deforestation, we used net forest conversion in Uganda. There was 94 % variation in the dependent variable (Net Forest conversion). The outcome of the dynamic linear regression showed that agriculture and energy emission positively impact net forest conversion. Based on our findings, this study recommended the modernization of agriculture by the government of Uganda to stop cutting down the forests on a big scale. Also, the study suggested that the government strictly legislate Roundwood and wood fuels/charcoal and firewood to reduce huge dependency on forests toward Zero-Deforestation by 2030. If well-structured and implemented, government policies could solve the unnecessary over dependency on the rainforest, the heart of the region's climatic conditions.

Carnivorous waterbirds have been reported to enhance wetlands diversities, control pests, bio-indicators of ecological conditions, and act as indicators of potential disease outbreaks. They also provide important ecosystem services to indigenous communities residing along wetlands. Regardless of their importance, global waterbirds populations are declining. Despite their ecological contribution to wetlands functions and ecosystem services, piscivore waterbirds have been re-ported to compete with piscivorous fish and fishermen. The aim of this study was to compare piscivorous waterbirds species and functional diversity between fish protected areas (FPA) and non-fish protected area (NFPA) in two tributaries of Zambezi River in Namibia. We also measured the degree to which patterns of guild structure between piscivore waterbirds and fish were similar between FPA and non-FPA. Species diversities were determined by calculating the Shannon Diversity Index. We calculated taxonomic diversity, functional diversity and community-based trait diversity indices for each tributary. Generally, species diversities were not significantly different between FPA and NFPA (P > 0.05). However, all functional diversities indices calculated were significantly different between FPA an NFPA (P < 0.05 for all comparisons). This was partly due to food item, weight and movement type that were associated with each site.

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.

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.

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.

Visible light photography diagnostic images are coloured ex vivo medical images popularly used in Dermatology and Endoscopy for diagnosis and monitoring. The need to protect the integrity of these images as well as associated patient data calls for techniques such as image steganography and watermarking. This research explores and compares the effect of watermarking on the YIQ and YCbCr colour transforms used in processing digital coloured images and video in recent times. Using a new spread spectrum watermarking algorithm, it was found that YIQ has better distortion performance than YCbCr in the order of 3dB while YCbCr had lower BER for accurate watermark retrieval and tamper detection in the order of 1.3 x 10-3.

Landform Evolution Modelling (LEM) provides an avenue for simulating how a landscape may evolve over extended time periods of thousands of years. The CAESAR-Lisflood LEM that includes a hydrologic model (TOPMODEL) and a hydraulic model (Lisflood) can be used to assess the proposed final landform morphology of a mine site by simulating how the mine landform and the landscape would evolve over a 1,000-year period. The accuracy of future simulations depends on the calibration and validation of the model to the past and present events. Calibration and validation of the model involves finding a combination of parameters of the model which when applied and simulated gives model outputs similar to those observed for the real site scenario for corresponding input data. Calibrating the sediment output of the CAESAR-Lisflood model at the catchment level and using it for studying the equilibrium conditions of the landform is an area yet to be explored. Therefore, the aim of this study was to calibrate the CAESAR-Lisflood model and then validate it. To achieve this, the model was run for a rainfall event with a set of parameters, plus discharge and sediment data for the input point of the catchment, to analyze how similar the model output would behave when compared with the discharge and sediment data for the output point of the catchment. The model parameters were then adjusted until the model closely approximate the real site values of the catchment. It was then validated by running the model for a different set of events and checking that the model gave similar results to the real site values. The outcomes demonstrated that while the model can be calibrated to a greater extent for hydrology (discharge output) throughout the year, the sediment output calibration may be slightly improved by having the ability to change parameters to take into account the seasonal vegetation growth during the start and end of the wet season. This study is important for designing and testing post-mining rehabilitated landscape systems that assess hydrology and sediment movement in seasonal biomes.

Many pilot-based initiatives have been developed to promote awareness and use of climate information services among vulnerable smallholder farmers in Africa through million-dollar investments. However, despite their experimental nature, these pilot projects have been successful in raising participating farmers’ awareness and use of climate information services and they can inform transferrable good practices. Through a systematic literature review approach, this review sought to understand ways in which these past pilot projects have contributed to climate risk management in the context of smallholder farming and the factors that led to their success. Results showed that climate information services main contribution to climate risk management has been through facilitating farm level decision making. Factors that led to success of the pilots include: use of downscaled information; building institutional partnerships to add value to climate information; involving farmers through the co-designing and co-developing process; face-to-face way of communication; embedding pre-seasonal workshops in the activities of local institutions for sustainability; using diversity of communication channels to enhance reach among others. These factors can be borrowed as good practices to inform future efforts focused on increasing adoption of climate information services among a wider population beyond pilot project reach.

With growing urbanisation the sustainability of cities has become increasingly important. Although cities have been using indicators for a long time it is only in the last decades that attempts have been made to collate indicators into indicator sets with the aim of reflecting the many different aspects that need to be covered to assess the sustainability of a city. The aim of this paper is to review how indicators for monitoring sustainable urban development have evolved over time and compare them to the indicators suggested by the UN Sustainable Development Goals (SDGs). The review reveals that previous indicator sets emphasised environmental sustainability, health and economic growth. It is also shown that indicator sets that pre-date the SDGs lacked dimensions such as gender equality and reduced inequalities. In all, the SDG indicators provide the possibility of a more balanced and integrated approach to urban sustainability monitoring. At the same time, a methodology is needed to facilitate the adaptation process of localising the SDGS, targets and indicators. Challenges of local application include their large number, their generic characteristics and the need to complement them with specific indicators that are more relevant at the city level.

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.

Background: HIV poses a threat to global health. With effective treatment options available, education and testing strategies are essential in preventing transmission. Text messaging is an effective tool for health promotion and can be used to target higher risk populations. This study reports on the design, delivery and testing of a mobile text messaging SMS intervention for HIV prevention and awareness, aimed at adults in the construction industry and delivered during the COVID-19 pandemic. Method: Participants were recruited at Test@Work workplace health promotion events (21 sites, n=464 employees), including health checks with HIV testing. Message development was based on a participatory design and included a focus group (n=9) and message fidelity testing (n=291) with assessment of intervention uptake, reach, acceptability, and engagement. Barriers to HIV testing were identified and mapped to the COM-B behavioural model. 23 one-way push SMS messages (19 included short web links) were generated and fidelity tested, then sent via automated SMS to two employee cohorts over a 10-week period during the COVID-19 pandemic. Engagement metrics measured were; opt-outs, SMS delivered/read, number of clicks per web link, and four two-way pull messages exploring repeat HIV testing, learning new information, perceived usefulness and behaviour change. Results: 291 people participated (68.3% of eligible attendees). A total of 7,726 messages were sent between March and June 2020, with 91.6% successfully delivered (100% read). 12.4% of participants opted out over 10 weeks. Of delivered messages, links were clicked an average of 14.4%, max 24.1% for HIV related links. The number of clicks on web links declined over time (r= -6.24, p=0.01). Response rate for two-way pull messages was 13.7% of participants. Since the workplace HIV test offer at recruitment, 21.6% reported having taken a further HIV test. Qualitative replies indicated behavioural influence of messaging on exercise, lifestyle behaviours and intention to HIV test. Conclusion: SMS messaging for HIV prevention and awareness is acceptable to adults in the construction industry, has high uptake, low attrition and good engagement with message content, when delivered during a global pandemic. Data collection methods may need refinement for audience and effect of COVID-19 on results is yet to be understood.

The application potential of cellulosic materials in natural composites and other fields needs to be explored to develop innovative, sustainable, lightweight, functional biomass materials that are also environmentally friendly. This study investigated Typha augostifolia (Typha sp.) as a potential new raw material for extracting cellulose nanocrystals (CNCs) for application in wastewater treatment composites. Alkaline treatments and bleaching were used to remove cellulose from the stem fibers. The CNCs were then isolated from the recovered cellulose using acid hydrolysis. The study showed a few distinct functional groups (O-H, -C-H, =C-H and C-O, and C-O-C) in the Fourier Transform Infrared (FTIR) spectra. Scanning electron microscope (SEM) revealed the smooth surface of CPC and CNCs that resulted from removing lignin and hemicellulose from powdered Typha augostifolia. Based on the crystalline index, the powdered Typha augostifolia, CPC, and CNCs were 42.86%, 66.94% and 77.41%. The loss of the amorphous section of the Typha sp. fiber resulted in a decrease in particle size. It may be inferred from the features of a Typha sp. CNC that CNCs may be employed as reinforcement in composites for wastewater treatment.

This study is part of a project designed to simulate the long-term landform equilibrium of a rehabilitated mine site. The project utilizes event fine suspended sediment (FSS) fluxes in a receiving stream following a rainfall event as an indicator of landform stability. The aim of this study was to use HEC-HMS to determine sediment and discharge quantity upstream to determine how it affects the downstream development of the catchment landform, in terms of sediment changes and geomorphology. Thus, the study focused on hydrology and sediment modelling of the upper catchment with HEC-HMS (Hydrologic Engineering Center-Hydrologic Modeling System) to determine daily discharge and sediment output at the catchment outlet. HEC-HMS was used to calibrate the stream discharge and FSS quantities at the catchment outlet to observed continuous discharge and FSS values. Calibration of the HEC-HMS model was done for two water years and then the same model parameters were used to validate the model for a third water year. Catchment discharge and FSS were calibrated and validated for continuous rainfall events against observed discharge and FSS data at the catchment outlet. The model was then run for a projected rainfall of 50 years. The denudation rate predicted by the model falls in the range previously determined for the region. The simulated sediment output was compared to the rainfall trends over the years. As a result, the sediment spikes following a rainfall-runoff event gradually decreased over time. Reducing FSS spikes indicate that the landform gradually attains stability. This modeling study can be used for long-term simulations to determine erosion equilibrium over the years and to quantify sediment yield in catchments for projected wet and dry rainfall scenarios.

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.

Incorporating ChatGPT into the classroom has several benefits that improve the educational experience for both teachers and students. ChatGPT seems useful in preparing students for success in the digital age, from personalized learning and increased instructional content to fostering collaboration, enabling bilingual classrooms, and encouraging creativity. This review offers insights regarding the perks of using ChatGPT in education as a tool for students. Among the many benefits of implementing ChatGPT in the classroom are enhanced accessibility, enhanced personalized learning, development of critical thinking skills, administrative support for educators, promotion of collaborative learning, and preparedness for a technologically advanced future. These advantages demonstrate how AI technologies have the capacity to drastically change teaching strategies and outcomes. While problems remain, the benefits of integrating ChatGPT in teaching are enormous. By integrating AI technology, educators may develop more dynamic and individualized learning environments that respond to the demands of 21st-century learners.

Mass crises are disruptive to people's mental health. The study aimed to explore mental distress during COVID-19 quarantine in a sample of university workers in Brazil. The survey included sets of questions about demographics, health, and support, an open question about major concerns, and the Clinical Outcome Routine Evaluation (CORE-OM), a measure of mental distress. 407 professionals participated in the study: mean age of 40 years (SD = 11.2), mostly female (67.8%), married (64.8%) and fulfilling social distancing to avoid COVID-19 infection (99%). Using the Consensual Qualitative Research for simple qualitative data (CQR-M) the main areas of concern were grouped into six domains, as follows: Work, Health, Isolation, Personal life and routine, Social environment, and Future. Many responses were multiple. They form categories indicating specific concerns within these domains. Quantitative data were analyzed by identifying the simple effects of potential predictors of mental distress. The results indicated medium effects of help with household chores, psychiatric treatment, age and physical exercise. Having someone available to listen was the only variable with a large effect in reducing mental suffering. The hybrid approach showed that the psychological experience during the pandemic is quite multifaceted and complex pointing new clues for public mental health.

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.

This study aligns with the 2030 United Nations Sustainable Development Goals- 3 which aim to “ensure healthy lives and promote well-being for all at all ages”. It contributes to the nascent literature stream on energy-health dynamics by introducing a holistic theoretical model to empirically examine the mediation effect of carbon emissions on the relationship between nonrenewable energy and infant mortality rates. Using an unbalanced panel data on 42 Asia and the Pacific countries from 2005 to 2015 and deploying the structural equation modeling approach, the empirical results are surmised as follows: (i) in regard to the full sample of countries, nonrenewable energy indirectly increases infant mortality rates through increasing carbon emissions. In other words, carbon emissions play a partial mediation role between nonrenewable energy and infant mortality rates; and (ii) for the different income groups, carbon emissions show varying mediation effects. For example, the mediation effects of carbon emissions in lower-middle and upper-middle income countries are found to be similar to those of the full sample of countries. Therefore, based on these findings, we conclude that nonrenewable energy is an essential determinant of infant mortality rates. Policy recommendations are put forward.

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.

Background: Craniofacial injuries are thought to be commonly associated with traumatic brain injury (TBI), but there is conflicting evidence in the literature. The objective of this retrospective cohort study is to evaluate the incidence of TBI in patients with craniofacial trauma. Methods: The study included 2982 consecutive patients with either solitary or concurrent diagnoses of TBI and facial fractures, seen and evaluated at a single level II trauma center between January 1, 2010 and December 31, 2020. Continuous variables were compared against whether the patient had one or both diagnoses.Results: Of the target population, 55.8% had a solitary diagnosis of TBI, 30.28% had a solitary diagnosis of facial fractures, and 13.92% had concurrent diagnoses of both TBI and facial fractures. Patients with concurrent diagnoses had a significantly longer mean length of stay (LOS) compared to those with solitary diagnoses (9.92 ± 16.33 days vs. 6.21 ± 10.96 days, p&lt;0.01), but age (p=0.68) and ICU LOS (p=0.09) did not differ significantly between the two groups. Conclusions: Trauma to the face should be given special attention due to the close relationship between facial bones and the brain. Patients with concurrent diagnoses of TBI and facial fractures had worse hospital outcomes than those with solitary diagnoses of either TBI or facial trauma.

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.

Precision medicine (PM), also termed stratified, individualised, targeted or personalised medicine, embraces a rapidly expanding area of research, knowledge, and practice. It brings together two emerging health technologies to deliver better individualised care: the many “-omics” arising from increased capacity to understand the human genome; and “big data” and data analytics including Artificial Intelligence (AI). PM has the potential to transform an individual’s health, moving from population-based disease prevention to more personalised management. There is however a tension between the two, with a real risk that this will exacerbate health inequalities and divert funds and attention from basic healthcare requirements leading to worse health outcomes for many. All areas of medicine should consider how this will affect their practice, with PM now strongly encouraged and supported by government initiatives and research funding. In this review we discuss examples of PM in current practice and its emerging applications in primary care, such as clinical prediction tools that incorporate genomic markers and pharmacogenomic testing. We look towards potential future applications and consider some key questions for PM including evidence of real-world impact, its affordability, the risk of exacerbating health inequalities, and the computational and storage challenges of applying PM technologies at scale.

The incidence of human papillomavirus-related head and neck squamous cell carcinoma (HPV+HNSCC) has reached epidemic levels in the last decade. While prophylactic vaccines will prevent future HPV infections, there are currently no HPV-specific antiviral drugs to treat current HPV infections or HPV+HNSCC. HPV replication and transcription are promising targets for anti-HPV therapeutics, as modulation of these processes can alter expression levels of HPV E6 and E7, which are required for maintenance of the transformed phenotype. This is a particularly attractive target in in HPV+HNSCC where the majority of tumors have episomal genomes replicating in an E1-E2 dependent manner. Here, we describe a model system to study HPV16 E1-E2 mediated DNA replication and HPV16 E2-mediated transcriptional activation and repression in multiple HNSCC cell lines. Our results demonstrate that low levels of IFIT1 are required for HPV16 replication in HNSCC cell lines and HPV16 E1 interacts with IFIT1. Restoration of IFIT1 expression in HNSCC cell lines partially inhibits HPV16 E1-E2 mediated replication. This system can be used to study replication and transcription by HPV16 E1 and E2 in HNSCC as well as be utilized to screen potential anti-HPV therapeutics that target HPV16 replication and transcription.

The aim of this work was to investigate a new, simple one-pot combustion synthesis technique for creating sulphur-based CuS/ZnS p-n heterojunction nanocomposite photocatalysts. The study examined the photocatalytic activity and reusability of these nanocomposites in removing rhodamine B (RhB) dye under visible light irradiation. Various methods of characterisation were employed to determine the properties of the materials, including particle morphology, crystalline phases and bandgap energy. The intrinsic reaction parameters, such as catalyst loading, pH level of the solution, and initial pollutant concentration, were varied to establish the optimal photo-degradation conditions. The results showed that a binary CuS/ZnS catalyst with a 10 gL-1 loading, at pH 5, degraded 97% of 5 ppm RhB dye after 270 minutes of visible light irradiation. Addition-ally, this composite catalyst exhibited excellent chemical stability and reusability, achieving 83% RhB dye removal after five recycling runs. Scavenger tests identified the photogenerated holes (h+) and superoxide free radicals (•O2) as the primary reactive species responsible for degradation. This study provides valuable insight into the design of highly efficient nanomaterials for removing organopollutants in wastewater, and a possible reaction mechanism is proposed.

There is need to address the challenges of organ shortage, through development of tissues and organs with alternatives to those of the allograft-kind. This illustrates the quest behind novel biofabrication strategies such as 3D bio-printing, which is necessary to create artificial multi-cellular tissues/organs. Several findings have been reported in this review. First, the role of ECM components in tissue regenerative medicine is presented. Different ECM components such as collagen, gelatin, elastin, fibronectin, laminins and glycosaminoglycans are concisely examined for their tissue regenerative medicine applications. Next, current state of research on extrusion-based 3D bio-printing techniques and their limitations are reviewed. For example, we show that cell viability is still a challenge with extrusion, while the use of natural polymers such as collagen in improving composites’ mechanical properties is limited. Lastly, we examine unresolved research questions necessary to advance the present state of research in the field.

Climate change has altered the frequency and severity of extreme weather, which can affect vegetation condition and habitat quality for wildlife. Declines in vegetation productivity during droughts and heatwaves can negatively impact animals that depend on vegetation for water and nutrition. The ability to detect such effects on habitat suitability can reveal refugia, which can be prioritised for protection to improve threatened species conservation. We used the normalised difference vegetation index (NDVI) to look at relationships between vegetation productivity and the presence of koalas (Phascolarctos cinereus) in potential habitat throughout much of their range. Using a large, long-term koala presence dataset, we tested the hypothesis that locations where koalas had been observed would exhibit higher NDVI values than a random, representative sample from the same vegetation group (i.e. woodlands, open forests or tall open forests). We also identified the minimum NDVI threshold at which koalas occurred across time for each vegetation group and compared these to the minimum NDVI values observed across potential koala habitat before and during the millennium drought; one of the worst recorded in Australia. Additionally, we investigated whether vegetation above the minimum NDVI thresholds was significantly closer to perennial water than unsuitable vegetation. We found that koalas tend to occur at locations exhibiting higher NDVI than average for all vegetation groups. We also found that 49% of all vegetation groups maintained a minimum NDVI above the koalas’ NDVI threshold before drought, equating to 190,227 km2, which declined to 166,746 km2 during drought (a 12% reduction). We also found that unsuitable vegetation tended to occur farther from perennial water than suitable vegetation for some vegetation groups. Areas that remained above the NDVI thresholds during the drought should be considered potential refugia for populations during an event of similar magnitude and could indicate future core habitat extent.

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.

Atherosclerosis is a chronic systemic inflammatory condition of the vasculature and a leading cause of stroke. Luminal stenosis severity is an important factor in determining vascular risk. Conventional imaging modalities, such as angiography or duplex ultrasonography, are used to quantify stenosis severity and inform clinical care but provide limited information on plaque biology. Inflammatory processes are central to atherosclerotic plaque progression and destabilization. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is a validated technique for quantifying plaque inflammation. In this review, we discuss the evolution of FDG-PET as an imaging modality to quantify plaque vulnerability, challenges to standardization of image acquisition and analysis, its potential application to routine clinical care after stroke, and the possible role it will play in future drug discovery.

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

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 paper we explore extending the concept of common cross-study Common Data Element concepts beyond simple demographics to cover disease-specific concepts relevant to imaging. We test interactively linking the resulting database to the associated images in a federated manner. We examine the use of existing standards, not only for terminology, but for interchange of serialized data in forms familiar to imaging and clinical trials specialists and their dedicated systems. Our intent is to perform preliminary work to inform both the upcoming Imaging Data Commons specifically, as well as more general integration projects beyond imaging.

(1) Background: Several agencies in the United States play a primary role in ensuring food safety, yet foodborne illnesses result in about 3,000 deaths and cost more than $15.6 billion each year. The study objectives included analyzing local health departments’ (LHDs) level of engagement in food safety and other related services, and LHDs’ characteristics associated with those services. (2) Methods: We used data from 1,496 LHDs that participated in the 2019 National Profile of Local Health Departments Survey, administered to all 2,459 LHDs in the United States. Logistic regression analyses were performed to model multiple dichotomous variables. (3) Results: An estimated 78.9% of LHDs performed food safety inspections, 78.3% provided food safety education, 40.7% provided food processing inspections, and 48.4% engaged in policy and advocacy. The odds for LHDs to directly provide preventive nutrition services were 20 times higher if the LHD had one or more nutritionists on staff (Adjusted Odds Ratio or AOR=20.0; Confidence Interval, CI=12.4-32.2) compared to LHDs with no nutritionists. Other LHD characteristics significantly associated with the provision of nutrition services (p&lt;.05) included population size, state governance (rather than local), and LHD having at least one registered, licensed, practical, or vocational nurse. The odds of providing food processing services were lower for locally governed than state governed LHDs (AOR=0.5; CI=0.4-0.7). The odds of performing food safety inspections varied by LHD’s population size, whether a nutritionist was on staff or not, state governance (vs. local), and having completed a community health assessment (CHA) within 5 years. (4) Conclusions: LHDs play a critical role in ensuring safe food for Americans, yet variations exist in their performance, based on their specific characteristics. Adequate funding and a competent workforce are essential for LHDs to utilize evidence-based practices and engage in policymaking and advocacy concerning food safety.

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.

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.

Feline immunodeficiency virus (FIV) is a lentivirus in the family Retroviridae that infects domestic cats resulting in an immunodeficiency disease featuring a progressive and profound decline in multiple sets of peripheral lymphocytes. Despite compelling evidence of FIV-associated immunopathology, there are conflicting data concerning the clinical effects of FIV infection on host morbidity and mortality. To explore FIV-associated immunopathogenesis and clinical disease, we experimentally inoculated a cohort of 4 specific pathogen free kittens with a biological isolate of FIV clade C and continuously monitored these animals along with 2 uninfected control animals for more than 13 years, from the time of inoculation to the humane euthanasia endpoint. Here we report the results obtained during the late asymptomatic and terminal phases of FIV infection in this group of experimentally FIV-infected cats.

The optimization of production of lignin-nanofiber-filled thermoplastic starch composite film for potential application in food packaging was carried using Response Surface Methodology (RSM), through the adoption of the Box-Wilson Central Composite Design (CCD) with 1 center point. The effects of filler loading on moisture absorption (MAB), tensile strength [TS], percent elongation [PE] and Young’s modulus [YM]) of the films were investigated in order to construct the desirability indices of the composite. The quality of the fitting model was expressed by the coefficient of determination, R2 and the adjusted R2. Results showed that the nanocomposite films were best fitted by a quadratic regression model with a high coefficient of determination (?2) value. The selected film has desirability of 76.80%, close to the objective function, and contained 4.81% lignin and 5.00% nanofibre. The MAB, TS, YM and PE of the selected film were 17.80 %, 21.51 MPa, 25.76 MPa and 48.81%, respectively. The addition of lignin and nanofiber to starch composite reduced the moisture absorption tendency but increased the mechanical properties of the films due to the good filler/matrix interfacial adhesion. Conclusively, results suggested that these films would be suitable for packaging application.

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.

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.

Interprofessional learning (IPL) is essential to prepare healthcare trainees as the future public health workforce. WHIRL was an innovative IPL intervention that engaged multi-professional teams of volunteer healthcare trainees (n=20) to deliver health checks (n=464), including tailored advice and signposting, to employees in the UK construction industry (across 21 events, 16 sites, 10 organisations) as part of an ongoing research programme called Test@Work. Volunteers undertook a four-part training and support package of trainer-led education, observations of practice, self-directed learning and clinical supervision, together with peer mentoring. In a one-group post-test only design, IPL outcomes were measured using the Inventory of Reflective Vignette - Interprofessional Learning (IRV-IPL), and the psychometric properties of the IRV-IPL tool were tested. WHIRL demonstrably improved healthcare trainees’ interprofessional skills in all five areas of collaboration, coordination, cooperation, communication, and commendation. The IRV-IPL tool was found to be a valid and reliable measure of interprofessional competencies across three scenarios; before and after health promotion activities, and as a predictor of future health promotion competence. This industry-based workplace IPL programme resulted in attainment of health check competencies, and bridged the gap between research, education and clinical practice.

Current commercially available instruments for monitoring mitochondrial respiration are incapable of single cell measurements. Therefore, we developed a three-electrode, Clark-type biosensor suitable for mitochondrial respirometry in single oocytes and embryos. The biosensor was embedded in a PMMA (polymethyl methacrylate) micro-chamber to allow investigation of single oocytes/embryos immersed in up to 100 µL of respiration buffer. The micro-chamber was completely sealed to avoid oxygen exchange between the inside of the chamber and the atmosphere, while being maintained at a temperature of 38.5 ˚C to preserve cell viability. Using amperometry, the oxygen consumption of cells inside the micro-chamber was measured as a change in output current and converted to femto-mol (fmol) oxygen consumed per second based on calibrations with known buffer oxygen concentrations. The sensor measured basal cell respiration supported by endogenous substrates, respiration associated with proton leak induced by inhibition of the adenosine triphosphate (ATP) synthase (complex V) with oligomycin, and the maximal non-coupled respiratory capacity revealed by Carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone (FCCP) titration. Some potential applications of this oxygen sensor system include evaluating effects of metabolic therapies on oocyte bioenergetics, and monitoring mitochondrial function throughout oocyte maturation and blastocyst development to predict embryo viability to compliment assisted reproductive technologies

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 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.

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

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.

Switchgrass (Panicum virgatum L.) remains the preeminent American perennial (C4) bioenergy crop for cellulosic ethanol that could help displace over a quarter of the US current petroleum consumption. Intriguingly, there is often little response to nitrogen fertilizer once stands are established. The rhizosphere microbiome plays a critical role in nitrogen cycling and overall plant nutrient uptake. We used high-throughput metagenomic sequencing to characterize the switchgrass rhizosphere microbial community (5.37 billion Illumina reads at 805 Gbp of data) before and after a nitrogen fertilization event for established stands on marginal land. We examined community structure, bulk metabolic potential, and resolved 29 individual bacteria genomes via metagenomic de novo assembly. Community structure and diversity were not significantly different before and after fertilization; however, the bulk metabolic potential of carbohydrate-active enzymes was depleted after fertilization. We resolved 29 metagenomic assembled genomes including some from the ‘most wanted’ soil taxa such as Verrucomicrobia, Candidate phyla UBA10199, Acidobacteria (rare subgroup 23), Dormibacterota, and the very rare Candidatus Eisenbacteria. The Dormibacterota (formally candidate division AD3) we identified have the potential for autotrophic CO utilization, which may impact carbon partitioning and storage. Our study also suggests that the rhizosphere microbiome may be involved in providing associative nitrogen fixation (ANF) via the novel diazotroph Janthinobacterium, which may partially explain why switchgrass growth is insensitive to fertilizer.

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.

Despite the availability of effective vaccines against COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide, pressing the need for new vaccines with improved breadth and durability. We developed an adjuvanted subunit vaccine against SARS-CoV-2 using recombinant receptor-binding domain (RBD) of spike with synthetic adjuvants targeting TLR7/8 (INI-4001) and TLR4 (INI-2002), co-delivered with aluminum hydroxide (AH) or aluminum phosphate (AP). The formulations were characterized for the quantities of RBD, INI-4001, and INI-2002 adsorbed onto the respective aluminum salts. Results indicated that at pH 6, the uncharged RBD (5.73 ± 4.2 mV) did not efficiently adsorb to the positively charged AH (22.68 ± 7.01 mV), whereas it adsorbed efficiently to the negatively-charged AP (-31.87 ± 0.33 mV). Alternatively, pre-adsorption of the TLR ligands to AH converted it to a negatively-charged particle, allowing for the efficient adsorption of RBD. RBD could also be directly adsorbed to AH at a pH of 8.1, which changed the charge of the RBD to negative. INI-4001 and INI-2002 efficiently to AH. Following vaccination in C57BL/6 mice, both aluminum salts promoted Th2-mediated immunity when used as the sole adjuvant. Co-delivery with TLR4 and/or TLR7/8 ligands efficiently promoted a switch to Th1-mediated immunity instead. Measurements of viral neutralization by serum antibodies demonstrated that the addition of TLR ligands to alum also greatly improved the neutralizing antibody response. These results indicate that the addition of a TLR7/8 and/or TLR4 agonist to a subunit vaccine containing RBD antigen and alum is a promising strategy for driving a Th1 response and neutralizing antibody titers targeting SARS-CoV-2.

The aim of this study was to establish the blood glucose response to different cooking methods of pasta. Participants consumed three identical meals in a random order that were freshly cooked (hot), cooled and reheated. Blood glucose concentrations were assessed before, and every 15 minutes after ingestion of each meal for 120 minutes. There was a significant interaction between temperature and time (F_{(8.46-372.34)} = 2.75, p = 0.005), with the reheated (90 minutes) condition returning to baseline faster than both cold (120 minutes) and hot conditions. Blood glucose AUC was significantly lower in the reheated (703 ± 56 mmol L^-1 min^-1) compared with the hot condition (735 ± 77 mmol L^-1 min^-1, t(92) = -3.36, pbonferroni = 0.003), with no significant difference with the cold condition (722 ± 62 mmol L^-1 min^-1). To our knowledge, the current study is the first to show that reheating pasta causes changes in post-prandial glucose response, with a quicker return to fasting levels in both the reheated and cooled conditions compared with the hot condition. The mechanisms behind the changes in post-prandial blood glucose seen in this study are most likely related to changes in starch structure and how these changes influence glycaemic response.

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.

We developed a honey bee RNA-virus vector based on the genome of a picorna-like Deformed wing virus (DWV), the main viral pathogen of the honey bee (Apis mellifera). To test the potential of DWV to be utilized as a vector, the 717 nt sequence coding for the enhanced green fluorescent protein (eGFP), flanked by the peptides targeted by viral protease, was inserted into an infectious cDNA clone of DWV in-frame between the leader protein and the virus structural protein VP2 genes. The in vitro RNA transcripts from egfp-tagged DWV cDNA clones were infectious when injected into honey bee pupae. Stable DWV particles containing genomic RNA of the recovered DWV with egfp inserts were produced, as evidenced by cesium chloride density gradient centrifugation. These particles were infectious to honey bee pupae when injected intra-abdominally. Fluorescent microscopy showed GFP expression in the infected cells and Western blot analysis demonstrated accumulation of free eGFP rather than its fusions with DWV LP and/or VP2 proteins. Analysis of the progeny egfp-tagged DWV showed gradual accumulation of genome deletions for egfp, providing estimates for the rate of loss of a non-essential gene an insect RNA virus genome during natural infection.

Background: The diagnosis of phenylketonuria (PKU) in an infant is a devastating and overwhelming event for their parents. Providing appropriate information and support is paramount, especially at the beginning of a child’s life. Investigating if parents are receiving the right support is important for their continued care. Methodology: An online survey was distributed to explore parents’ perceptions of current support and information provided by their healthcare provider and to rate sources of other support (n=169 participants). Results: Dietitians received the highest (85%) rate of “very helpful” support. Overall, parents found Facebook to be helpful for support, but had mixed reactions when asked if healthcare professionals (HCPs) should provide advice as part of the groups. When rating the most effective learning methods, the top three were: 1:1 sessions (n=109, 70%), picture books (n=73, 50%) and written handouts (n=70, 46%). Conclusion: Most parents were happy with the support and information they received from their dietitian, but required more support from other HCPs. Facebook groups provide parents with the social support that HCPs and their family may be unable to offer, suggesting a place for social media in future PKU care.

Systematic reviews of 591 primary studies of the modes of transmission for SARS-CoV-2 show significant methodological shortcomings and heterogeneity in the design, conduct, testing and reporting of SARS-CoV-2 transmission. While this is partly understandable at the outset of a pandemic, evidence rules of proof for assessing the transmission of this virus are needed for pre-sent and future pandemics of viral respiratory pathogens. We review the history of causality as-sessment related to microbial etiologies with a focus on respiratory viruses and suggest a hierar-chy of evidence to integrate clinical, epidemiologic, molecular and laboratory perspectives on transmission. The hierarchy, if applied to future studies, should narrow the uncertainty over the twin concepts of causality and transmission of human respiratory viruses. We attempt to address the translational gap between the current research evidence and the assessment of causality in the transmission of respiratory viruses with a focus on SARS-CoV-2. Experimentation, consistency and independent replication of research alongside our proposed framework provide a chain of evidence that can reduce the uncertainty over the transmission of respiratory viruses and increase the level of confidence in specific modes of transmission, informing the measures that should be undertaken to prevent transmission.

In vitro glucose uptake in yeast cell facilitated by Abelmoschus esculentus L. (okra seed) for management of type 2 diabetes was studied. Plant material was collected, identified, processed, and stored for further use. 80% methanol was employed for extraction and sonicated to release antidiabetic-bioactive component in solution and was filtered, concentrated, freeze-dried, and fractionated using standard techniques. Glucose uptake at an initial concentration of 5mM/L and 10mM/L by the crude extract was consistent to that of the known standard drug while at 25mM/L glucose concentration was equivalent with the crude extract. Also, at 0.625 mg/mL the linear equations, and R2 demonstrations that the crude extract was higher in dose predictability than the standard drug as presented by the equation; y = 35.754x - 57.822, and R² = 0.9502 (95%). The extract-fractions were employed to evaluate the ability of yeast cell line culture to take up glucose from the system through DPPH, FRAP, lipid peroxidation and anti-diabetes effect of extract-fraction assays. Extract-fractions were found to poses antioxidant activity high enough to inhibit stress-related diseases. The extract fractions were active as drug candidates both at low and high concentrations and were better compared with the standard drug and standard antioxidant was comparable. The high bioactive extract fractions require encapsulation with a nanoparticle as a drug candidate for type 2 diabetes patients. And an animal trial of the drug candidate may be necessary to monitor the in vivo performances of the extract fractions and subsequent human volunteered trial.

We assessed the use of Evidence-Based Practice (EBP) among pharmacists working in community pharmacies in France, and the factors linked to this practice. During 3 months in 2018 an online survey was sent to over 7,000 active pharmacists, and posted on pharmacist social media sites. The 40-item questionnaire described four clinical cases reflecting typical situations (conventional med-icine and Complementary and Alternative Medicine) encountered daily by community pharma-cists. Multiple-choice responses were proposed and scored according to whether they reflected EBP. A high total score indicated behavior in line with EBP. Univariate and multivariate analyses were used to evaluate factors that might explain adherence to EPB (pharmacy’s characteristics, the pharmacist’s status, mode of continuing education and sources of information). 595 pharmacists completed the questionnaire. The majority relied on pharmaceutical industry and other biased and/or non-evidence-based sources, particularly concerning information on homeopathic products. The consultation of independent reviews, health agency recommendations, and peer-reviewed scientific journals, was associated with evidence-based decisions. In contrast, reliance on phar-maceutical industry documents, personal experience and informal handbooks was linked to lower EBP scores. The level of EBP use by French community pharmacists needs to be improved to ensure that good quality scientifically-based advice is given to customers.

Six-Transmembrane Epithelial Antigen of the Prostate 1-4 (STEAP1-4) compose a family of metalloproteinases involved in iron and copper homeostasis and other cellular processes. Thus far, five homologs are known: STEAP1, STEAP1B, STEAP2, STEAP3, and STEAP4. In prostate cancer, STEAP1, STEAP2, and STEAP4 are overexpressed while STEAP3 expression is downregulated. Although the metalloreductase activities of STEAP1-4 are well-documented, their other biological functions are not. Furthermore, the properties and expression levels of STEAP heterotrimers, homotrimers, heterodimers, and homodimers are not well-understood. Nevertheless, studies over the last few decades have provided sufficient impetus to investigate STEAP1-4 as potential biomarkers and therapeutic targets for prostate cancer. In particular, STEAP1 is the target of many emerging immunotherapies. Herein, we give an overview of the structure, physiology, and pathophysiology of STEAP1-4 to provide context for past and current efforts to translate STEAP1-4 into the clinic.

In semi-arid regions, climate change has affected crop growing season length and sowing time, potentially causing low yield of the rainfed staple crop pearl millet (Pennisetum glaucum L.) and food insecurity among smallholder farmers. In this study, we used 1994–2023 rainfall data from Namibia's semi-arid North-Central Region (NCR), receiving November–April summer rainfall, to analyze rainfall patterns and trends and their implications on the growing season to propose climate adaptation options for the region. The results revealed high annual and monthly rainfall variabilities, with nonsignificant negative trends for November–February rainfalls, implying a shortening growing season. Furthermore, we determined the effects of sowing date on grain yields of the early-maturing Okashana-2 and local landrace Kantana pearl millet varieties and the optimal sowing window for the region, using data from a two-year split-plot field experiment conducted at the University of Namibia-Ogongo Campus, NCR, during the rainy season. Cubic polynomial regression models were applied to grain yield data sets to predict grain production for any sowing date between January and March. Both varieties produced the highest grain yields under January sowings, with Kantana exhibiting a higher yield potential than Okashana-2. Kantana, sown by 14 January, had a yield advantage of up to 36.0% over Okashana-2, but its yield gradually reduced with delays in sowing. Okashana-2 exhibited higher yield stability across January sowings, surpassing Kantana’s yields by up to 9.4% following the 14 January sowing. We determined the pearl millet optimal sowing window for the NCR from 1–7 and 1–21 January for Kantana and Okashana-2, respectively. These results suggest that co-cultivation of early and late pearl millet varieties and growing early-maturing varieties under delayed seasons could stabilize grain production in northern Namibia and enhance farmers' climate adaptation. Semi-arid agro-region policymakers could utilize this information to adjust local seed systems and extension strategies.

Co-delivery of antigens and adjuvants to the same antigen presenting cells (APCs) can significantly improve the efficacy and safety profiles of vaccines. Here, we report amine-grafted silica nanoparticles (A-SNPs) as a tunable vaccine co-delivery platform for TLR7/8 agonists along with the recombinant influenza antigen hemagglutinin H7 (H7) to APCs. A-SNPs of two different sizes (50 and 200 nm) were prepared and coated with INI-4001 at different coating densities, followed by co-adsorption of H7. Both INI-4001 and H7 showed &gt; 90% adsorption to the tested A-SNP formulations. TNF-α and IFN-α cytokine release by human peripheral blood mononuclear cells as well as TNF-α, IL-6, and IL-12 release by mouse bone marrow-derived dendritic cells revealed that the potency of the INI-4001-adsorbed A-SNPs (INI-4001/A-SNP) formulations can be improved relative to aqueous formulation control. This improved potency was dependent on particle size and ligand coating density. In addition, slow-release profiles of INI-4001 were measured from INI-4001/A-SNP formulations in plasma with 30-50% INI-4001 released after 7 days. In vivo murine immunization studies demonstrated significantly improved H7-specific humoral and Th1/Th17-polarized T cell immune responses with no observed adverse reactions. Low-density 50 nm INI-4001/A-SNP elicited significantly higher IFN-γ and IL-17 induction over that of the H7 antigen only group and INI-4001 aqueous formulation controls. In summary, this work introduces an effective and biocompatible SNP-based co-delivery platform that enhances the immunogenicity of TLR7/8 agonist-adjuvanted subunit influenza vaccines.

Recent dramatic reductions in the timeframe in which genomic sequencing can deliver results means its application in time-sensitive screening programs such as newborn screening (NBS) is becoming a reality. As genomic NBS (gNBS) programs are developed around the world, there is an increasing need to address the ethical and social issues that such initiatives raise. This study therefore aimed to explore the Australian public’s perspectives and values regarding key gNBS characteristics and preferences for service delivery. We recruited English-speaking members of the Australian public over 18 years of age via social media; 75 people aged 23-72 participated in one of 15 focus groups. Participants were generally supportive of introducing genomic sequencing into newborn screening, with several stating that adoption of such revolutionary and beneficial technology was a moral obligation. Participants consistently highlighted receiving an early diagnosis as the leading benefit, which was frequently linked to the potential for early treatment and intervention, or access to other forms of assistance, such as peer support. Informing parents about the test during pregnancy was considered important. This study provides insights into the Australian public’s views and preferences to inform the delivery of a gNBS program in the Australian context.

Development of K-Ras independence may explain failure of targeted therapy for pancreatic cancer (PC). In this paper active N as well as K-Ras was shown in all human cell lines tested. In a cell line dependent on mutant K-Ras, it was shown that depleting K-Ras reduced total Ras activity, while cell lines described as independent had no significant decline in total Ras activity. Knockdown of N-Ras showed it had an important role in controlling the relative level of oxidative metabolism but only K-Ras depletion caused a decrease in G2 cyclins, proteasome inhibition reversed this and other targets of APC/c were also decreased by K-Ras depletion. K-Ras depletion did not cause an increase in ubiquitinated G2 cyclins but instead caused exit from G2 phase to slow relative to completion of S-phase, suggesting mutant K-Ras may inhibit APC/c prior to anaphase but stabilizes G2 cyclins independently of this. We propose that during tumorigenesis, cancer cells expressing wild type N-Ras protein are selected because the protein protects cancer cells from the deleterious effects of cell cycle independent induction of cyclins by mutant K-Ras. Mutation independence results when N-Ras activity becomes adequate to drive cell division even in cells where K-Ras is inhibited. Keywords: Pancreatic Ductal Adenocarcinoma, K-Ras, N-Ras, G2 cyclins.

This study explores how young people’s mental health was affected by the COVID-19 pandemic using artwork and semi-structured interviews. This is important to understand so that policy and practice professionals can support those affected, prepare, and respond to future crises, and support young people who are isolated and restricted in other contexts. Co-designed participatory art workshops and interviews were conducted with 16–18-year-olds (N = 21) from the London-based Longitudinal cohort Study of Cognition, Adolescents and Mobile Phones (SCAMP). Artworks and interview transcripts were qualitatively co-analysed with young people. From interviews, six themes were identified: adaptation, restriction, change, challenges, overcoming adversity, and lockdown life. From artwork, four themes were identified; trapped, negative mental wellbeing, positive emotions, and technology. Everyday factors such as home environment, relationships, hobbies, habits, and education or work were key determinants of how challenged and restricted participants felt, and their capacity to overcome this. This implies that young people’s mental health services should collaborate with other sectors to address wider life determinants in a holistic way, and that clearer guidance and support in these areas could mitigate the negative mental health impacts of major environmental changes on young people.

The morphology, internal architecture, and emplacement mechanisms of the Central Atlantic Magmatic Province (CAMP) lava flows of the Hartford and Deerfield basins (USA) are presented. The Talcott, Holyoke, and Hampden formations within the Hartford basin constitute distinct basaltic units, each exhibiting chemical, mineralogical, and structural differences corresponding to flow fields. Each flow field was the result of several sustained eruptions that produced both inflated pahoehoe flows and subaquatic extrusions: 1–5 eruptions in the Talcott formation and 1-2 in Holyoke and Hampden basalts, where simple flows are dominant. The Deerfield basin displays the Deerfield basalt unit, characterized by pillow lavas and sheet lobes, aligning chemically and mineralogically with the Holyoke basalt unit. Overall, the studied flow fields are composed of thick, simple pahoehoe flows that display the entire range of pahoehoe morphology, including inflated lobes. The three-partite structure of sheet lobes, vertical distribution of vesicles, and segregation structures are typical. The characteristics of the volcanic pile suggest slow emplacement during sustained eruptive episodes and are compatible with a continental basaltic succession facies model. The studied CAMP basalts of the eastern United States are correlated with the well-exposed examples on both sides of the Atlantic Ocean (Canada, Portugal, and Morocco).

ELTD1 is expressed in endothelial and vascular smooth muscle cells and has a role in angiogenesis. It has been classified as an adhesion GPCR, but as yet, no ligand has been identified and its function remains unknown. To establish its role, ELTD1 was overexpressed in endothelial cells. Expression and consequently ligand independent activation of ELTD1 results in EndMT with a loss of cell-cell contact, formation of stress fibres and mature focal adhesions and an increased expression of smooth muscle actin. The effect was pro-angiogenic, increasing Matrigel network formation and endothelial sprouting. RNA-Seq analysis after the cells had undergone EndMT revealed large increases in chemokines and cytokines involved in regulating immune response. Gene set enrichment analysis of the data identified a number of pathways involved in myofibroblast biology suggesting that the endothelial cells had undergone a type II EMT. This type of EMT is involved in wound repair and is closely associated with inflammation implicating ELTD1 in these processes.

Gene editing tools such as CRISPR-Cas9 have created unprecedented opportunities for genetic studies in plants and animals. We designed a course-based undergraduate research experience (CURE) to train introductory biology students in the concepts and implementation of gene editing technology as well as develop their soft skills in data management and scientific communication. We present two versions of the course that can be implemented with twice-weekly meetings over a five-week period. In the remote-learning version, students perform homology searches, design guide RNAs and primers, and learn the principles of molecular cloning. This version is appropriate when access to laboratory equipment or in-person instruction is limited, such as closures that have occurred in response to the Covid-19 pandemic. In the in-person version, students design guide RNAs, clone CRISPR-Cas9 constructs, and perform genetic transformation of the model plant Arabidopsis thaliana. The highly parallel nature of the CURE makes it possible to target dozens to hundreds of genes, depending on the number of course sections available. Applying this approach in a sensitized mutant background enables focused reverse genetic screens for genetic suppressors or enhancers. The course can be readily adapted to other organisms or projects that employ gene editing.

In most industrialized countries, screening programs for cervical cancer have shifted from cytology (Pap smear or ThinPrep) alone on clinician-obtained samples to the addition of screening for human papillomavirus (HPV), its main causative agent. For HPV testing, self-sampling instead of clinician-sampling has proven to be equally accurate, in particular for assays that use nucleic acid amplification techniques. In addition, HPV testing of self-collected samples in combination with a follow-up Pap smear in case of a positive result is more effective in detecting precancerous lesions than a Pap smear alone. Self-sampling for HPV testing has already been adopted by some countries, while others have started trials to evaluate its incorporation into national cervical cancer screening programs. Self-sampling may result in more individuals willing to participate in cervical cancer screening, because it removes many of the barriers that prevent women, especially those in low socioeconomic and minority populations, from participating in regular screening programs. Several studies have shown that the majority of women who have been underscreened but who tested HPV-positive in a self-obtained sample, will visit a clinic for follow-up diagnosis and management. Additionally, a self-collected sample can also be used for vaginal microbiome analysis, which can provide additional information about HPV infection persistence as well as vaginal health in general.

Radiomics involves the extraction of information from medical images not visible to the human eye. There is evidence these features can be used for treatment stratification and outcome prediction. However, there is much discussion about the reproducibility of results between different studies. This paper studies the reproducibility of CT texture features used in radiomics, comparing two feature extraction implementations namely Matlab toolkit and Pyradiomics when applied on independent datasets of CT scans of patients i) the open access RIDER dataset containing a set of repeat CT scans taken 15 minutes apart for 31 patients (RIDER Scan 1 and Scan 2 respectively) treated for lung cancer and ii) the open access HN1 dataset containing 137 patients treated for head and neck cancer. Gross tumor volume (GTV) manually outlined by an experienced observer available on both datasets was used. 43 common radiomics features available on Matlab and Pyradiomics were calculated using 2 intensity-level quantization methods with and without an intensity threshold. Cases were ranked for each feature for all combinations of quantization parameters and the Spearman’s rank coefficient, rs, calculated. Reproducibility was defined when a highly correlated feature in the RIDER dataset also correlated highly in the HN1 dataset and vice versa. 29 out of 43 reported stable features were found to be highly reproducible between Matlab and Pyradiomics implementations, having consistently high correlation in rank ordering for RIDER Scan 1 and RIDER Scan 2 (rs &gt; 0.8). 18/43 reported features were common in RIDER and HN1 datasets, suggesting they may be agnostic to disease site. Useful radiomics features should be selected based on reproducibility. This study identified a set of features that meet this requirement and validated the methodology for evaluating reproducibility between datasets.

Technological advances in game-mediated robotics provide an opportunity to engage children with cerebral palsy (CP) and other neuromotor disabilities in more frequent and intensive therapy by making personalized, programmed interventions available 24/7 in children’s homes. Though shown to be clinically effective and feasible to produce, little is known of the subjective factors impacting acceptance of what we term assistive/rehabilitative (A/R) gamebots by their target populations. This research describes the conceptualization phase of an effort to develop a valid and reliable instrument to guide the design of A/R gamebots. We conducted in-depth interviews with 8 children with CP and their families who had trialed an exemplar A/R gamebot, PedBotHome, for 28 days in their homes. The goal was to understand how existing theories and instruments were either appropriate or inappropriate for measuring the subjective experience of A/R gamebots. Key findings were the importance of differentiating the use case of therapy from that of assistance in rehabilitative technology assessment, the need to incorporate the differing perspectives of children with CP and those of their parents into A/R gamebot evaluation, and the potential conflict between the goals of preserving the quality of the experience of game play for the child while also optimizing the intensity and duration of therapy provided during play.

Genome-wide association studies have revealed a locus at 8p12 that is associated with breast cancer risk. Fine-mapping of this locus identified 16 candidate causal variants (CCVs). However, as these variants are intergenic, their function is unclear. To map chromatin looping from this risk locus to a previously identified candidate target gene, DUSP4, we performed chromatin conformation capture analyses in normal and tumoral breast cell lines. We identified putative regulatory elements, containing CCVs, that loop to the DUSP4 promoter region. Using reporter gene assays, we found that the risk allele of CCV rs7461885 reduced the activity of a DUSP4 enhancer element, consistent with the function of DUSP4 as a tumor suppressor gene. Furthermore, the risk allele of CCV rs12155535, located in another DUSP4 enhancer element, was negatively correlated with looping of this element to the DUSP4 promoter region, suggesting that this allele would be associated with reduced expression. These findings provide the first evidence that CCV risk alleles downregulate DUSP4 expression, suggesting that this gene is a regulatory target of the 8p12 breast cancer risk locus.

Apicomplexan infections, such as giardiasis and cryptosporidiosis, negatively impact a considerable proportion of human and commercial livestock populations. Despite this, the molecular mecha-nisms of disease, particularly the effect on the body beyond the gastrointestinal tract, are still poorly understood. To highlight host-parasite-microbiome biochemical interactions, we utilised integrated metabolomics-16S rRNA genomics and metabolomics-proteomics approaches in a C57BL/6J mouse model of giardiasis and compared these to Cryptosporidium and uropathogenic Escherichia coli (UPEC) infections. Comprehensive samples (faeces, blood, liver, and luminal contents from duo-denum, jejunum, ileum, caecum and colon) were collected 10 days post infection and subjected to proteome and metabolome analysis by liquid and gas chromatographic mass-spectrometry, re-spectively. Microbial populations in faeces and luminal washes were examined using 16S rRNA metagenomics. Proteome-metabolome analyses indicated that 12 and 16 key pathways were sig-nificantly altered in the gut and liver, respectively, during giardiasis with respect to other infections. Energy pathways including glycolysis and supporting pathways of glyoxylate and dicarboxylate metabolism, and redox pathway of glutathione metabolism, were upregulated in small intestinal luminal contents and the liver during giardiasis. Metabolomics-16S rRNA genetics integration in-dicated that populations of three bacterial families –Autopobiaceae (Up), Desulfovibrionaceae (Up) and Akkermanasiaceae (Down) – were most significantly affected across the gut during giardiasis, causing upregulated glycolysis and short-chained fatty acid (SCFA) metabolism. In particular, the perturbed Akkermanasiaceae population seemed to cause oxidative stress responses along the gut-liver axis. Overall, the systems biology approach applied in this study highlighted that the effects of host-parasite-microbiome biochemical interactions extended beyond the gut ecosystem to the gut-liver axis. These findings form the first steps in a comprehensive comparison to ascertain the major molecular and biochemical contributors of host-parasite interactions and contribute towards the development of biomarker discovery and precision health solutions for apicomplexan infections.

Cryptosporidiosis is a major human health concern globally. Despite well-established methods, misdiagnosis remains common. Our understanding of the cryptosporidiosis biochemical mechanism remains limited, compounding the difficulty of clinical diagnosis. Here, we used a systems biology approach to investigate the underlying biochemical interactions in C57BL/6J mice infected with Cryptosporidium parvum. Faecal samples were collected daily following infection. Blood, liver tissues and luminal contents were collected 10 days post infection (dpi). High-resolution liquid chromatography and low-resolution gas chromatography coupled with mass spectrometry were used to analyse the proteomes and metabolomes of these samples. Faeces and luminal contents were additionally subjected to 16S rRNA gene sequencing. Univariate and multivariate statistical analysis of the acquired data illustrated altered host and microbial energy pathways during infection. Glycolysis/citrate cycle metabolites were depleted, while short-chain fatty acids and D-amino acids accumulated. An increased abundance of bacteria associated with a stressed gut environment was seen. Host proteins involved in energy pathways and Lactobacillus glyceraldehyde-3-phosphate dehydrogenase were upregulated during cryptosporidiosis. Liver oxalate also increased during infection. Microbiome-parasite relationships were observed to be more influential than the host-parasite association in mediating major biochemical changes in the mouse gut during cryptosporidiosis. Defining this parasite-microbiome interaction is the first step towards building a comprehensive cryptosporidiosis model towards biomarker discovery, and rapid and accurate diagnostics.

Lymphatic filariasis (LF), also commonly known as elephantiasis, is a neglected tropical disease (NTD) caused by filarial parasites. The disease is transmitted by a bite from infected mosquitoes. The bites of these infected mosquitoes deposit filarial parasites, Wuchereria or Brugia whose predilection site is the lymphatic system. The damage to the lymph system causes swelling in the legs, arms, and genitalia. A mapping survey conducted between 2003 and 2010 determined LF that LF was endemic in Zambia in 96 out of 116 districts. Elimination of LF is known to be possible by stopping the spread of the infection through large-scale preventive chemotherapy. Therefore, mass drug administration (MDA) with diethylcarbamazine citrate (DEC) (6 mg/kg) and Albendazole (400 mg) for Zambia has been conducted and implemented in all endemic districts with five effective rounds. Post-MDA pre-transmission assessment survey (pre-TAS) was conducted between 2021 and 2022 in 80 districts to determine the LF prevalence rate. We conducted a cross-sectional seroprevalence study involving 600 participants in each Evaluation Unit (EU) or each district. The study sites (sentinel and spot-check sites) were the districts that were the Implementation Unites (IUs) where MDA, preventive chemotherapy against LF was conducted. These included 80 districts from the 9 provinces. A total of 47,235 people from sentinel and spot-check locations were tested. Of these, valid tests were 47,052 of which 27,762 (59%) were females and 19,290 (41%) were males. The survey revealed in the 79/80 endemic district a prevalence of Wb anti-gens of 0.14% and 0.0% prevalence of microfilariae. All the surveyed districts had an optimum prevalence of less than 2 percent, except for Chibombo district. The majority of participants that tested positive for Wb Ag were those that had 2, 3, and 4 rounds of MDA. Surprisingly, individuals that had 1 round of MDA were not found to have circulating antigens of Wb. The study showed that all the surveyed districts except for Chibombo, passed Pre-TAS. This further implies that there is a need to conduct a TAS in these districts in order to decide whether to stop MDA or not. Keywords: Lymphatic Filariasis; pre-TAS; Prevalence; Antigenaemia; Microfilariae; Zambia

An important stage in SARS-CoV-2 life cycle is the fusion of spike(S) protein with the ACE2 host-cell receptor. Therefore, to explore conserved features in S protein dynamics and to identify potentially novel regions for drugging, we measured variability derived from 791 viral genomes and studied its properties by MD simulation. The findings indicated that S2 subunit (HR1, CH, and CD domains) showed low variability, low fluctuations in MD, and displayed a trimer cavity. By contrast, the RBD domain, which is typically targeted in drug discovery programmes, exhibits more sequence variability and flexibility. Interpretations from MD suggest that the monomer is in constant motion showing transitions up-to-down state, and the trimer cavity may function as a 'bouncing spring' that may facilitates S protein interactions with ACE2. Feasibility of trimer cavity for potential drug target was examined by SBVS screening. Several hits that have already been validated or suggested to inhibit the SARS-CoV-2 virus in cell systems were identified; in particular, the data suggest an action mechanism for such molecules including Chitosan and macrolide types. These findings identify a novel binding-site formed by the S protein, that might assist in future drug discovery programmes aimed at targeting the CoV family of viruses.

Type-2 diabetes mellitus (T2DM) have been strongly associated with single nucleotide polymorphisms (SNPs) in the TCF7L2 gene. This study investigated the association between rs12255372, rs7903146 and T2DM in a Ghanaian population. A case-control study design was used for this study. A total of 106 T2DM patients and 110 control participants were selected. Basic data collected included body mass index, blood pressure and socio-demographics. Fasting blood samples were collected and used for serum lipid analysis, HbA1c, plasma glucose estimation and DNA extraction. Common and allele-specific primers were designed for genotyping using the Modified Tetra-Primer Amplification assay. Associations were evaluated using logistic regression models. The rs7903146 risk variant was significantly associated with 2.16 vs 4.06 increased odds for T2DM in patients <60 years vs ≥60 years. Both rs7903146 and rs12255372 are significantly associated with increased odds of T2DM in women, overweight/obese; T2DM negative family history (T2DM-NFH) and low-HDL-C. In a multivariate model, rs7903146 but not rs12255372 was significantly associated with 2.18, 5.01 and 2.25 increased odds of T2DM, under the codominant, recessive and additive model, respectively (p<0.05). The association between rs7903146 and rs12255372 with T2DM is more highly associated in a subgroup- women and those with T2DM-NFH, yet have cardiometabolic risk.

Histoplasmosis is one of the most underdiagnosed and underreported endemic mycoses in the United States. Histoplasma capsulatum is the causative agent of this disease. To date, molecular epidemiologic studies detailing the phylogeographic structure of H. capsulatum in the United States have been limited. We conducted genomic sequencing using isolates from histoplasmosis cases reported in the United States. We identified North American Clade 2 (NAm2) as the most prevalent clade in the country. Despite high intra-clade diversity, isolates from Minnesota and Michigan cases predominately clustered by state. Future work incorporating environmental sampling and veterinary surveillance may further elucidate the molecular epidemiology of H. capsulatum in the United States and how genomic sequencing can be applied for surveillance and outbreak investigation of histoplasmosis.

Nebulized thrombolysis offers locally targeted therapy with potentially lower bleeding risk than systemic administration for coronavirus disease 2019 (COVID-19) respiratory failure. In a proof-of-concept safety study, adult patients with COVID-19-induced respiratory failure and a <300mmHg PaO2/FiO2 (P/F) ratio, requiring invasive mechanical ventilation (IMV) or non-invasive respiratory support (NIRS) received nebulized rt-PA in two cohorts (C1 and C2), alongside standard of care during the first two UK COVID-19 waves. Matched historical controls (MHC; n=18) were used in C1. Safety co-primary endpoints were treatment-related bleeds and fibrinogen reduction to <1.0–1.5 g/L. A dose escalation strategy for improved efficacy with the least safety concerns was determined in C1 for use in C2; patients were stratified by ventilation type to receive 40–60 mg rt-PA per day for ≤14 days. Nine patients in C1 (IMV, 6/9; NIRS, 3/9) and 26 in C2 (IMV, 12/26; NIRS, 14/26) received nebulized rt-PA for a mean (SD) of 6.7 (4.6) and 9.1(4.6) days, respectively. Four bleeding events (one severe and three mild) in three patients were considered treatment-related. No significant fibrinogen reductions were reported. Greater improvement in mean P/F ratio from baseline to end of study was observed in C1 compared with MHC [C1; 154 to 299 vs MHC; 154 to 212). In C2, there was no difference in the baseline P/F ratio of NIRS and IMV patients. However, a larger improvement in P/F ratio was observed in NIRS patients [NIRS; 126 to 240 vs IMV; 120 to 188) and they required fewer treatment days (NIRS; 7.86 vs IMV; 10.5). Nebulized rt-PA appears to be well-tolerated, showing a trend of improved oxygenation and faster recovery in patients with acute COVID-19-induced respiratory failure requiring respiratory support; this effect was more pronounced in the NIRS group. Further investigation is required to study the potential of this novel treatment approach.