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Animal feed ingredients, especially those abundant in high quality protein, are the most expensive component of livestock production. Sustainable alternative feedstocks may be sourced from abundant, low value agricultural byproducts. California almond production generates nearly 3 Mtons of biomass per year with about 50% in the form of hulls. Almond hulls are a low-value byproduct currently used primarily for animal feed for dairy cattle. However, the protein and essential amino acid content are low, at ~30% d.b.. The purpose of this study was to improve the protein content and quality using yeast. To achieve this, the almond hulls were liquefied to liberate soluble and structural sugars. A multi-phase screening approach was used to identify yeasts that can consume a large proportion of the sugars in almond hulls while accumulating high concentrations of amino acids essential for livestock feed. Compositional analysis showed that almond hulls are rich in polygalacturonic acid (pectin) and soluble sucrose. A pectinase-assisted process was optimized to liquefy and release soluble sugars from almond hulls. The resulting almond hull slurry containing solubilized sugars was subsequently used to grow high-protein yeasts that could consume nutrients in almond hulls while accumulating high concentrations of high-quality protein rich in essential amino acids needed for livestock feed, yielding a process that would produce 72 mg protein/g almond hull. Further work is needed to achieve conversion of galacturonic acid to yeast cell biomass.

Pneumococcal conjugate vaccines reduce the burden of invasive pneumococcal disease, but the sustained effect of these vaccines can be diminished by an increase in disease caused by non-vaccine serotypes. To describe pneumococcal serotype epidemiology in Botswana following introduction of 13-valent pneumococcal conjugate vaccine (PCV-13) in July 2012, we performed molecular serotyping of 268 pneumococcal strains isolated from 221 children between 2012 and 2017. The median (interquartile range) age of the children included in this analysis was 6 (3,12) months. Fifty-nine percent of the children had received at least one dose of PCV-13 and 35% were fully vaccinated with PCV-13. While colonization by vaccine serotypes steadily declined following PCV-13 introduction, 25% of strains isolated more than 3 years after vaccine introduction were PCV-13 serotypes. We also observed an increase in colonization by non-vaccine serotypes 21 and 23B, which have been associated with invasive pneumococcal disease and antibiotic resistance in other settings.

Animal affective computing is an emerging new field, which has so far mainly focused on pain, while other emotional states remain uncharted territories, especially in horses. This study is the first to develop AI models to automatically recognize horse emotional states from facial expressions using data collected in a controlled experiment. We explore two types of pipelines: a deep learning one which takes as input video footage, and a machine learning one which takes as input EquiFACS annotations. The former outperforms the latter, with 76% accuracy in separating between four emotional states: baseline, positive anticipation, disappointment and frustration. Anticipation and frustration were difficult to separate, with only 61% accuracy.

The island of Guam in the west Pacific has seen a significant decrease in coral cover since 2013. Lafac Bay, a marine protected area in northeast Guam, served as a reference site for benthic communities typical of forereefs on the windward side of the island. The staghorn coral Acropora abrotanoides is a dominant and characteristic ecosystem engineer of forereef communities on exposed shorelines. Photoquadrat surveys were conducted in 2015, 2017, and 2019, and a diver-operated hyperspectral imager (i.e., DiveRay) was used to survey the same transects in 2019. Machine learning algorithms were used to develop an automated pipeline to assess the benthic cover of 10 biotic and abiotic categories in 2019 based on hyperspectral imagery. The cover of scleractinian corals did not differ between 2015 and 2017 despite being subjected to a series of environmental disturbances in these years. Surveys in 2019 documented the almost complete decline of the habitat-defining staghorn coral Acropora abrotanoides (a practically complete disappearance from about 10% cover), a significant decrease (~75%) in the cover of other scleractinian corals, and a significant increase (~55%) in the combined cover of bare substrate, turf algae, and cyanobacteria. The drastic change in community composition suggests that the reef at Lafac Bay is transitioning to a turf algae-dominated community. However, the capacity of this reef to recover from previous disturbances suggests that this transition could be reversed, making Lafac Bay an excellent candidate for long-term monitoring. Community analyses showed no significant difference between automatically classified benthic cover estimates derived from the hyperspectral scans in 2019 and those derived from photoquadrats. These findings suggest that underwater hyperspectral imagers can be efficient and effective tools for fast, frequent, and accurate monitoring of dynamic reef communities.

Archaeological systematics, together with spatial and chronological information, are commonly used to infer cultural evolutionary dynamics in the past. For the study of the Palaeolithic, and particularly the European Final Palaeolithic and earliest Mesolithic, proposed changes in material culture are often interpreted as reflecting historical processes, migration, or cultural adaptation to climate change and resource availability. Yet, cultural taxonomic practice is known to be variable across research history and academic traditions, and few large-scale replicable analyses across such traditions have been undertaken. Drawing on recent developments in computational archaeology, we here present a data-driven assessment of the existing Final Palaeolithic/earliest Mesolithic cultural taxonomy in Europe. Our dataset consists of a large expert-sourced compendium of key sites, lithic toolkit composition, blade and bladelet production technology, as well as lithic armatures. The dataset comprises 16 regions and 86 individually named archaeological taxa ('cultures'), covering the period between ca. 15,000 and 11,000 years ago (cal BP). Using these data, we use geometric morphometric and multivariate statistical techniques to explore to what extent the dynamics observed in different lithic data domains (toolkits, technologies, armature shapes) correspond to each other and to the culture-historical relations of taxonomic units implied by traditional naming practice. Our analyses support the widespread conception that some dimensions of material culture became more diverse towards the end of the Pleistocene and the very beginning of the Holocene. At the same time, cultural taxonomic unit coherence and efficacy appear variable, leading us to explore potential biases introduced by regional research traditions, inter-analyst variation, and the role of disjunct macroevolutionary processes. In discussing the implications of these findings for narratives of cultural change and diversification across the Pleistocene-Holocene transition, we emphasize the increasing need for cooperative research and systematic archaeological analyses that reach across research traditions.

Sudden changes in sound and light (e.g., sirens and flashing police beacons) are a common component of working dogs' on-duty environment. Yet, how such stimuli impact dogs' ability to perform physical and cognitive tasks has not been explored. To address this shortcoming, we compared the accuracy and time taken for twelve dogs to complete a complex physical and cognitive task, before, during and after exposure to three 'real-world' stimuli: an acoustic distractor (85dB), white strobe lighting (5, 10 & 15 Hz), and exposure to a dazzling white, red, or blue lights. We found that strobe lighting, and to a greater extent, acoustic distraction, significantly reduced dogs' physical performance. Acoustic distraction also tended to impair dogs' cognitive performance. Dazzling lights had no effect on task performance. Most (nine out of twelve) dogs sensitised to the acoustic distraction to the extent of non-participation in the rewarded task. Our results suggest that without effective distractor response training, sudden changes in noise and flickering lights are likely to impede cognitive and physical task performance in working dogs. Repeated uncontrolled exposure may also amplify these effects.

IntroductionSupporting adolescents with their health and wellbeing is an international public health priority. Schools are well placed to universally detect unmet health needs and support pupils. This study aimed to evaluate the effectiveness of a digital health and wellbeing screening tool, called the 'Digital Health Contact' (DHC) implemented in schools in the East Midlands of England. The DHC, delivered by Public Health Nurses (School Nurses) (PHN(SN)), aims to identify pupils with unmet health needs (via a 'red flag' system) and provide appropriate support.Materials and methodsUsing data from 22 schools which took part in the DHC and 14 schools which did not take part, across three academic years (2018-2020), we conducted a controlled interrupted timeseries analysis with negative binomial regression to explore the effect of the DHC on the number of annual referrals to PHN(SN). Using DHC data from 164 pupils, we further conducted a Difference-in-Difference analysis to explore the impact of 'red flag' and referral via the DHC in Year 9 (age 13-14) on the number of red flags in Year 11 (age 15-16).ResultsAcross all schools, the mean annual number of referrals increased over the three year follow-up period. In the adjusted model, the number of referrals was comparable between schools taking part in the DHC and non-participating schools (0.15 referrals [95% CI -0.21, 0.50]). Red flag score was not significantly different among Year 11 pupils, after being referred via the DHC in Year 9 (-0.36 red flags [95% CI -0.97, 0.24]).DiscussionThe DHC, and similar screening tools, have the potential to raise awareness of the health and wellbeing support in schools and provide an additional pathway of referral to this support for pupils with unmet health needs, without replacing the traditional pathway where pupils refer themselves or are referred by teachers.

Islet autoantibodies are predominantly measured by radioassay to facilitate risk assessment and diagnosis of type 1 diabetes. However, the reliance on radioactive components, large sample volumes and limited throughput renders radioassay testing costly and challenging. We developed a multiplex analysis platform based on antibody detection by agglutination-PCR (ADAP) for the sample-sparing measurement of GAD, IA-2 and insulin autoantibodies/antibodies in 1 μL serum. The assay was developed and validated in 7 distinct cohorts (n = 858) with the majority of the cohorts blinded prior to analysis. Measurements from the ADAP assay were compared to radioassay to determine correlation, concordance, agreement, clinical sensitivity and specificity. The average overall agreement between ADAP and radioassay was above 91%. The average clinical sensitivity and specificity were 96% and 97%. In the IASP 2018 workshop, ADAP achieved the highest sensitivity of all assays tested at 95% specificity (AS95) rating for GAD and IA-2 autoantibodies and top-tier performance for insulin autoantibodies. Furthermore, ADAP correctly identified 95% high-risk individuals with two or more autoantibodies by radioassay amongst 39 relatives of T1D patients tested. In conclusion, the new ADAP assay can reliably detect the three cardinal islet autoantibodies/antibodies in 1μL serum with high sensitivity. This novel assay may improve pediatric testing compliance and facilitate easier community-wide screening for islet autoantibodies.

Marine phytoplankton are responsible for approximately half of photosynthesis on Earth. However, their ability to drive ocean productivity depends on critical nutrients, especially bioavailable nitrogen (N) which is scarce over vast areas of the ocean. Phytoplankton differ in their preferences for N substrates as well as uptake efficiencies and minimal N requirements relative to other critical nutrients, including iron (Fe) and phosphorus. In this study, we used the MicroTOOLs high-resolution environmental microarray to examine transcriptomic responses of phytoplankton communities in the California Current System (CCS) transition zone to added urea, ammonium, nitrate, and also Fe in the late summer when N depletion is common. Transcript level changes of photosynthetic, carbon fixation, and nutrient stress genes indicated relief of N limitation in many strains of Prochlorococcus, Synechococcus, and eukaryotic phytoplankton. The transcriptomic responses helped explain shifts in physiological and growth responses observed later. All three phytoplankton groups had increased transcript levels of photosynthesis and/or carbon fixation genes in response to all N substrates. However, only Prochlorococcus had decreased transcript levels of N stress genes and grew substantially, specifically after urea and ammonium additions, suggesting that Prochlorococcus outcompeted other community members in these treatments. Diatom transcript levels of carbon fixation genes increased in response to Fe but not to Fe with N which might have favored phytoplankton that were co-limited by N and Fe. Moreover, transcription patterns of closely related strains indicated variability in N utilization, including nitrate utilization by some high-light adapted Prochlorococcus. Finally, up-regulation of urea transporter genes by both Prochlorococcus and Synechococcus in response to filtered deep water suggested a regulatory mechanism other than classic control via the global N regulator NtcA. This study indicated that co-existing phytoplankton strains experience distinct nutrient stresses in the transition zone of the CCS, an understudied region where oligotrophic and coastal communities naturally mix.

Islet autoantibodies are predominantly measured by radioassay to facilitate risk assessment and diagnosis of type 1 diabetes. However, the reliance on radioactive components, large sample volumes and limited throughput renders radioassay testing costly and challenging. We developed a multiplex analysis platform based on antibody detection by agglutination-PCR (ADAP) for the sample-sparing measurement of GAD, IA-2 and insulin autoantibodies/antibodies in 1 μL serum. The assay was developed and validated in 7 distinct cohorts (n = 858) with the majority of the cohorts blinded prior to analysis. Measurements from the ADAP assay were compared to radioassay to determine correlation, concordance, agreement, clinical sensitivity and specificity. The average overall agreement between ADAP and radioassay was above 91%. The average clinical sensitivity and specificity were 96% and 97%. In the IASP 2018 workshop, ADAP achieved the highest sensitivity of all assays tested at 95% specificity (AS95) rating for GAD and IA-2 autoantibodies and top-tier performance for insulin autoantibodies. Furthermore, ADAP correctly identified 95% high-risk individuals with two or more autoantibodies by radioassay amongst 39 relatives of T1D patients tested. In conclusion, the new ADAP assay can reliably detect the three cardinal islet autoantibodies/antibodies in 1μL serum with high sensitivity. This novel assay may improve pediatric testing compliance and facilitate easier community-wide screening for islet autoantibodies.

Over half of all children with autism spectrum disorders (ASD) have gastrointestinal (GI) co-morbidities including chronic constipation, diarrhea, and irritable bowel syndrome. The severity of these symptoms has been correlated with the degree of GI microbial dysbiosis. The study objective was to assess tolerability of a probiotic (Bifidobacterium infantis) in combination with a bovine colostrum product (BCP) as a source of prebiotic oligosaccharides and to evaluate GI, microbiome and immune factors in children with ASD and GI co-morbidities. This pilot study is a randomized, double blind, controlled trial of combination treatment (BCP + B. infantis) vs. BCP alone in a cross-over study in children ages 2-11 with ASD and GI co-morbidities (n = 8). This 12-week study included 5 weeks of probiotic-prebiotic supplementation, followed by a two-week washout period, and 5 weeks of prebiotic only supplementation. The primary outcome of tolerability was assessed using validated questionnaires of GI function and atypical behaviors, along with side effects. Results suggest that the combination treatment is well-tolerated in this cohort. The most common side effect was mild gassiness. Some participants on both treatments saw a reduction in the frequency of certain GI symptoms, as well as reduced occurrence of particular aberrant behaviors. Improvement may be explained by a reduction in IL-13 and TNF-α production in some participants. Although limited conclusions can be drawn from this small pilot study, the results support the need for further research into the efficacy of these treatments.

Sublethal effects of oil spills may dampen seabird rehabilitation success due to lingering negative impacts of contamination and stress on reproduction and long-term survival. These effects can be difficult to measure while birds are in care as well as once birds are released. Expression of sexually selected traits that are sensitive to condition can provide information on physiological status of birds. We evaluated plumage molt and gular pouch skin color of California brown pelicans (Pelecanus occidentalis californicus) following oil contamination and rehabilitation to test for differences between previously oiled and rehabilitated (post-spill) and presumably uncontaminated pelicans. Post-spill pelicans released with either color leg bands alone, or bands plus harness-mounted satellite GPS tags, were relocated and visually assessed in the field at non-breeding communal roosts and compared to surrounding unmarked pelicans in the general population. Non-oiled pelicans bearing GPS tags were also included in the study. Post-spill pelicans lagged the general population in molt of ornamental yellow crown feathers but hind neck transition into white plumage was not significantly different. Both post-spill and non-oiled pelicans wearing GPS tags had lower gular redness scores than the unmarked, non-oiled population. Pre-breeding gular pouch redness of post-spill pelicans was more strongly influenced by wearing of a GPS tag than a history of oil contamination and rehabilitation. Gular pouch redness of post-spill pelicans in the first 18 months after release was positively correlated with long term survivorship. If gular pouch color is a condition-dependent sexual signal and overall health influences plumage molt progression, our results indicate that many post-spill pelicans marked with bands alone were in relatively good condition going into the next breeding season, but those released with electronic tags experienced additional stress due to wearing the equipment, introducing a confounding variable to the post-release study.

Camera traps are a key tool in ecological studies, and are increasingly being used to understand entire communities. However, robust inferences continue to be hampered by low detection of rare and elusive species. Attractants can be used to increase detection rates, but may also alter behaviour, and little research has evaluated short-term, localized response to the presence of attractants. We conducted three camera trap surveys in Kibale National Park, Uganda, using food baits and scent lures ("attractants") at each camera station to entice small carnivores to pass in front of camera stations. To examine the interrelationship between scavenging and response to attractants, we also placed camera traps at five food refuse pits. We modelled the effect of attractant and duration of trap placement on the detection probability of small carnivores and selected African golden cat Caracal aurata prey items. We examine transient site response of each species, by comparing our observed likelihood of detection in each 24 h period from 1-7 d following refreshing of attractants to randomly generated capture histories. African civet Civettictis civetta, rusty-spotted genet Genetta maculata, African palm civet Nandinia binotata, and marsh mongoose Atilax paludinosus detection probabilities were highest and Weyns's red duiker Cephalophus wenysi detection probability was lowest immediately after attractants were placed. Within 24 h after attractant was placed, rusty-spotted genet and African palm civet were more likely to be detected and African golden cat, red duiker, and blue duiker Philantomba monticola were less likely to be detected. Our results suggest that attractants can increase detection of small-bodied species and include some arboreal species in terrestrial camera trap sampling. However, attractants may also alter short-term visitation rates of some species, with potentially cascading effects on others. Community level and intraguild interaction studies should control for the potentially confounding effects of attractants on spatial activity patterns.

The prebiotic potential of nervine herbal medicines has been scarcely studied. We therefore used anaerobic human fecal cultivation to investigate whether medicinal herbs commonly used as treatment in neurological health and disease in Ayurveda and other traditional systems of medicine modulate gut microbiota. Profiling of fecal cultures supplemented with either Kapikacchu, Gotu Kola, Bacopa/Brahmi, Shankhapushpi, Boswellia/Frankincense, Jatamansi, Bhringaraj, Guduchi, Ashwagandha or Shatavari by 16S rRNA sequencing revealed profound changes in diverse taxa. Principal coordinate analysis highlights that each herb drives the formation of unique microbial communities predicted to display unique metabolic potential. The relative abundance of approximately one-third of the 243 enumerated species was altered by all herbs. Additional species were impacted in an herb-specific manner. In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring. Collectively, our results indicate that gut microbiota engage in both protein and glycan catabolism, providing amino acid and sugar substrates that are consumed by fermentative species. We identified taxa that are efficient amino acid fermenters and those capable of both amino acid and sugar fermentation. Herb-induced microbial communities are predicted to alter the relative abundance of taxa encoding SCFA (butyrate and propionate) pathways. Co-occurrence network analyses identified a large number of taxa pairs in medicinal herb cultures. Some of these pairs displayed related culture growth relationships in replicate cultures highlighting potential functional interactions among medicinal herb-induced taxa.

Animal feed ingredients, especially those abundant in high quality protein, are the most expensive component of livestock production. Sustainable alternative feedstocks may be sourced from abundant, low value agricultural byproducts. California almond production generates nearly 3 Mtons of biomass per year with about 50% in the form of hulls. Almond hulls are a low-value byproduct currently used primarily for animal feed for dairy cattle. However, the protein and essential amino acid content are low, at ~30% d.b.. The purpose of this study was to improve the protein content and quality using yeast. To achieve this, the almond hulls were liquefied to liberate soluble and structural sugars. A multi-phase screening approach was used to identify yeasts that can consume a large proportion of the sugars in almond hulls while accumulating high concentrations of amino acids essential for livestock feed. Compositional analysis showed that almond hulls are rich in polygalacturonic acid (pectin) and soluble sucrose. A pectinase-assisted process was optimized to liquefy and release soluble sugars from almond hulls. The resulting almond hull slurry containing solubilized sugars was subsequently used to grow high-protein yeasts that could consume nutrients in almond hulls while accumulating high concentrations of high-quality protein rich in essential amino acids needed for livestock feed, yielding a process that would produce 72 mg protein/g almond hull. Further work is needed to achieve conversion of galacturonic acid to yeast cell biomass.

IntroductionHealthcare-associated infections (HAIs) are a global health challenge, particularly in low- and middle-income countries (LMICs). Infection prevention and control (IPC) remains an important strategy for preventing HAIs and improving the quality of care in hospital wards. The social environment and interactions in hospital wards are important in the quest to improve IPC. This study explored care practices and the interactions between healthcare providers and mothers in the neonatal intensive care units (NICU) in two Ghanaian hospitals and discusses the relevance for IPC.MethodologyThis study draws on data from an ethnographic study using in-depth interviews, focus group discussions involving 43 healthcare providers and 72 mothers, and participant observations in the wards between September 2017 and June 2019. The qualitative data were analysed thematically using NVivo 12 to facilitate coding.FindingsMothers of hospitalized babies faced various challenges in coping with the hospital environment. Mothers received sparse information about their babies' medical conditions and felt intimidated in the contact with providers. Mothers strategically positioned themselves as learners, guardians, and peers to enable them to navigate the clinical and social environment of the wards. Mothers feared that persistent requests for information might result in their being labelled "difficult mothers" or might impact the care provided to their babies. Healthcare providers also shifted between various positionings as professionals, caregivers, and gatekeepers, with the tendency to exercise power and maintain control over activities on the ward.ConclusionThe socio-cultural environment of the wards, with the patterns of interaction and power, reduces priority to IPC as a form of care. Effective promotion and maintenance of hygiene practices require cooperation, and that healthcare providers and mothers find common grounds from which to leverage mutual support and respect, and through this enhance care for mothers and babies, and develop stronger motivation for promoting IPC.

Melanomas from gynecologic sites (MOGS) are rare and have poor survival. MicroRNAs (miRs) regulate gene expression and are dysregulated in cancer. We hypothesized that MOGS would display unique miR and mRNA expression profiles. The miR and mRNA expression profile in RNA from formalin fixed, paraffin embedded vaginal melanomas (relative to vaginal mucosa) and vulvar melanomas (relative to cutaneous melanoma) were measured with the Nanostring Human miRNA assay and Tumor Signaling mRNA assay. Differential patterns of expression were identified for 21 miRs in vaginal and 47 miRs in vulvar melanoma (fold change >2, p

Various methods have been developed to combine inference across multiple sets of results for unsupervised clustering, within the ensemble clustering literature. The approach of reporting results from one 'best' model out of several candidate clustering models generally ignores the uncertainty that arises from model selection, and results in inferences that are sensitive to the particular model and parameters chosen. Bayesian model averaging (BMA) is a popular approach for combining results across multiple models that offers some attractive benefits in this setting, including probabilistic interpretation of the combined cluster structure and quantification of model-based uncertainty. In this work we introduce clusterBMA, a method that enables weighted model averaging across results from multiple unsupervised clustering algorithms. We use clustering internal validation criteria to develop an approximation of the posterior model probability, used for weighting the results from each model. From a combined posterior similarity matrix representing a weighted average of the clustering solutions across models, we apply symmetric simplex matrix factorisation to calculate final probabilistic cluster allocations. In addition to outperforming other ensemble clustering methods on simulated data, clusterBMA offers unique features including probabilistic allocation to averaged clusters, combining allocation probabilities from 'hard' and 'soft' clustering algorithms, and measuring model-based uncertainty in averaged cluster allocation. This method is implemented in an accompanying R package of the same name. We use simulated datasets to explore the ability of the proposed technique to identify robust integrated clusters with varying levels of separation between subgroups, and with varying numbers of clusters between models. Benchmarking accuracy against four other ensemble methods previously demonstrated to be highly effective in the literature, clusterBMA matches or exceeds the performance of competing approaches under various conditions of dimensionality and cluster separation. clusterBMA substantially outperformed other ensemble methods for high dimensional simulated data with low cluster separation, with 1.16 to 7.12 times better performance as measured by the Adjusted Rand Index. We also explore the performance of this approach through a case study that aims to identify probabilistic clusters of individuals based on electroencephalography (EEG) data. In applied settings for clustering individuals based on health data, the features of probabilistic allocation and measurement of model-based uncertainty in averaged clusters are useful for clinical relevance and statistical communication.

Genetic engineering of animals has been proposed to address societal problems, but public acceptance of the use of this technology is unclear. Previous work has shown that the source of information proposing the technology (e.g. companies, universities), the term used to describe the technology (e.g. genome editing, genetic modification), and the genetic engineering application (e.g. different food products) affects technology acceptance. We conducted three mixed-method surveys and used a causal trust-acceptability model to understand social acceptance of genetic engineering (GE) by investigating 1) the source of information proposing the technology, 2) the term used to describe the technology, and 3) the GE application for farm animals proposed. Further, participants expressed their understanding of technology using a range of terms interchangeably, all describing technology used to change an organism’s DNA. We used structural equation modelling and confirmed model fit for each survey. In each survey, perceptions of benefit had the greatest effect on acceptance. Following our hypothesized model, social trust had an indirect influence on acceptance through similar effects of perceived benefit and perceived risk. Additional quantitative analysis showed that the source of information and technology term had little to no effect on acceptance. Applications involving animals were perceived as less beneficial than a plant application, and an application for increased cattle muscle growth was perceived as more risky than a plant application. When assessing the acceptability of applications participants considered impacts on plants, animals, and people, trust in actors and technologies, and weighed benefits and drawbacks of GE. Future work should consider how to best measure acceptability of GE for animals, consider contextual factors and consider the use of inductive frameworks.

The efficacy of using human volatile organic compounds (VOCs) as a form of forensic evidence has been well demonstrated with canines for crime scene response, suspect identification, and location checking. Although the use of human scent evidence in the field is well established, the laboratory evaluation of human VOC profiles has been limited. This study used Headspace-Solid Phase Microextraction-Gas Chromatography-Mass Spectrometry (HS-SPME-GC-MS) to analyze human hand odor samples collected from 60 individuals (30 Females and 30 Males). The human volatiles collected from the palm surfaces of each subject were interpreted for classification and prediction of gender. The volatile organic compound (VOC) signatures from subjects' hand odor profiles were evaluated with supervised dimensional reduction techniques: Partial Least Squares-Discriminant Analysis (PLS-DA), Orthogonal-Projections to Latent Structures Discriminant Analysis (OPLS-DA), and Linear Discriminant Analysis (LDA). The PLS-DA 2D model demonstrated clustering amongst male and female subjects. The addition of a third component to the PLS-DA model revealed clustering and minimal separation of male and female subjects in the 3D PLS-DA model. The OPLS-DA model displayed discrimination and clustering amongst gender groups with leave one out cross validation (LOOCV) and 95% confidence regions surrounding clustered groups without overlap. The LDA had a 96.67% accuracy rate for female and male subjects. The culminating knowledge establishes a working model for the prediction of donor class characteristics using human scent hand odor profiles.

During the COVID-19 pandemic, the reduced exports and imports as well as the lack of activity due to the interruption in the international tourism economy seriously impacted food security in many Pacific Islands. People often returned to natural resources to provide for themselves, their families, or to generate income. On Bora-Bora Island, the major tourist destination in French Polynesia, roadside sales are widespread. Our study analyses the impact of the COVID-19 pandemic on roadside sales activities through a census of roadside stalls on the five Bora-Bora districts conducted before (January and February 2020), during (from March 2020 to October 2021) and after (from November to December 2021) health-related activity and travel restrictions. Our results showed that the marketing system for local products (fruits, vegetables, cooked meals, and fish) increased in the form of roadside sales during the COVID-19 in two of the five districts of Bora-Bora. Roadside selling would be an alternative system for providing food to the population at Bora-Bora during a global crisis and that could reveal itself sustainable after this pandemic.

Necrotizing enterocolitis (NEC) remains the leading cause of gastrointestinal morbidity and mortality in premature infants. Human and animal studies suggest a role for Paneth cells in NEC pathogenesis. Paneth cells play critical roles in host-microbial interactions and epithelial homeostasis. The ramifications of eliminating Paneth cell function on the immature host-microbial axis remains incomplete. Paneth cell function was depleted in the immature murine intestine using chemical and genetic models, which resulted in intestinal injury consistent with NEC. Paneth cell depletion was confirmed using histology, electron microscopy, flow cytometry, and real time RT-PCR. Cecal samples were analyzed at various time points to determine the effects of Paneth cell depletion with and without Klebsiella gavage on the microbiome. Deficient Paneth cell function induced significant compositional changes in the cecal microbiome with a significant increase in Enterobacteriacae species. Further, the bloom of Enterobacteriaceae species that occurs is phenotypically similar to what is seen in human NEC. This further strengthens our understanding of the importance of Paneth cells to intestinal homeostasis in the immature intestine.

The science of meditation has grown tremendously in the last two decades. Most studies have focused on evaluating the clinical effectiveness of mindfulness-based interventions, neural and other physiological correlates of meditation, and individual cognitive and emotional aspects of meditation. Far less research has been conducted on more challenging domains to measure, such as group and relational, transpersonal and mystical, and difficult aspects of meditation; anomalous or extraordinary phenomena related to meditation; and post-conventional stages of development associated with meditation. However, these components of meditation may be crucial to people's psychological and spiritual development, could represent important mediators and/or mechanisms by which meditation confers benefits, and could themselves be important outcomes of meditation practices. In addition, since large numbers of novices are being introduced to meditation, it is helpful to investigate experiences they may encounter that are not well understood. Over the last four years, a task force of meditation researchers and teachers met regularly to develop recommendations for expanding the current meditation research field to include these important yet often neglected topics. These meetings led to a cross-sectional online survey to investigate the prevalence of a wide range of experiences in 1120 meditators. Results show that the majority of respondents report having had many of these anomalous and extraordinary experiences. While some of the topics are potentially controversial, they can be subjected to rigorous scientific investigation. These arenas represent largely uncharted scientific terrain and provide excellent opportunities for both new and experienced researchers. We provide suggestions for future directions, with accompanying online materials to encourage such research.

BackgroundThe human breast comprise several ductal systems, or lobes, which contain a small amount of fluid containing cells, hormones, proteins and metabolites. The complex physiology of these ducts is likely a contributing factor to the development of breast cancer, especially given that the vast majority of breast cancers begin in a single lobular unit.MethodsWe examined the levels of total protein, progesterone, estradiol, estrone sulfate, dehydroepiandrosterone sulfate, and macrophages in ductal fluid samples obtained from 3 ducts each in 78 women, sampled twice over a 6 month period. Samples were processed for both cytological and molecular analysis. Intraclass correlation coefficients and mixed models were utilized to identify significant data.ResultsWe found that the levels of these ductal fluid components were generally uncorrelated among ducts within a single breast and over time, suggesting that each lobe within the breast has a distinct physiology. However, we also found that estradiol was more correlated in women who were nulliparous or produced nipple aspirate fluid.ConclusionsOur results provide evidence that the microenvironment of any given lobular unit is unique to that individual unit, findings that may provide clues about the initiation and development of ductal carcinomas.

BackgroundAlthough micronutrient and antioxidant supplementation are widely used by persons with human immunodeficiency virus (HIV), a therapeutic role beyond recommended daily allowances (RDA) remains unproven. An oral high-dose micronutrient and antioxidant supplement (Treatment) was compared to an RDA supplement (Control) for time to progressive immunodeficiency or initiation of antiretroviral therapy (ART) in people living with HIV (PLWH).MethodsThis study was a randomized, double-blind, placebo-controlled multicenter clinical trial. PLWH were recruited from Canadian HIV Trials Network sites, and followed quarterly for two years. Eligible participants were asymptomatic, antiretroviral treatment (ART)-naïve, HIV-seropositive adults with a CD4 T lymphocyte count (CD4 count) between 375-750 cells/μL. Participants were randomly allocated 1:1 to receive Treatment or Control supplements. The primary outcome was a composite of time-to-first of confirmed CD4 count below 350 cells/μL, initiation of ART, AIDS-defining illness or death. Primary analysis was by intention-to-treat. Secondary outcomes included CD4 count trajectory from baseline to ART initiation or two years. A Data and Safety Monitoring Board reviewed the study for safety, recruitment and protocol adherence every six months.ResultsOf 171 enrolled participants: 66 (38.6%) experienced a primary outcome: 27 reached a CD4 count below 350 cells/μL, and 57 started ART. There was no significant difference in time-to-first outcome between groups (Hazard Ratio = 1.05; 95%CI: 0.65, 1.70), or in time to any component outcome. Using intent-to-treat censoring, mean annualized rates of CD4 count decline were -42.703 cells/μL and -79.763 cells/μL for Treatment and Control groups, with no statistical difference in the mean change between groups (-37.06 cells/μL/52 weeks, 95%CI: (-93.59, 19.47); p = 0.1993). Accrual was stopped at 171 of the 212 intended participants after an interim analysis for futility, although participant follow-up was completed.ConclusionsIn ART-naïve PLWH, high-dose antioxidant, micronutrient supplementation compared to RDA supplementation had no significant effect on disease progression or ART initiation.Clinical trial registrationClinicalTrials.gov Identifier: NCT00798772.

Suicide capability is theorised to facilitate the movement from suicidal ideation to suicide attempt. Three types of contributors are posited to comprise suicide capability: acquired, dispositional, and practical. Despite suicide capability being critical in the movement from ideation-to-attempt, there has been no systematic synthesis of empirical evidence relating to suicide capability that would enable further development and refinement of the concept. This study sought to address this synthesis gap. A scoping review was conducted on suicide capability studies published January 2005 to January 2022. Eleven electronic databases and grey literature sources were searched returning 5,212 potential studies. After exclusion criteria application, 90 studies were included for final analysis. Results synthesis followed a textual narrative approach allocating studies based on contributors of suicide capability. Most studies focused on investigating only one factor within contributors. Painful and provocative events appear to contribute to acquired capability more so than fearlessness about death. Whilst emerging evidence for dispositional and practical contributors is promising, the small number of studies prevents further conclusions from being drawn. An unexpected additional cognitive contributor was identified. The focus of a single factor from most studies and the limited number of studies on contributors other than acquired capability limits the theoretical development and practical application of suicide capability knowledge. Given that suicide is a complex and multifaceted behaviour, future research that incorporates a combination of contributors is more likely to advance our understandings of suicide capability.

The anonymity that the internet and social media affords users means that suicidal thoughts and/or behaviours can be talked about with a sense of freedom and disinhibition that is often not possible in face-to-face contexts. Better understanding online suicidal thoughts and/or behaviour talk is critical as more people turn to online spaces for support. Without this the potentiality of such spaces as sites for suicide prevention and intervention is likely to remain unrealised. Currently there are no scoping or systematic review syntheses focusing on internet and/or on social media suicidal thoughts and/or behaviour talk. This lack of synthesis is problematic as it makes it more difficult for online suicide prevention and intervention practices, policies, and our understanding of suicide to advance in a coherent and evidence-based manner. A scoping review protocol following Arksey and O'Malley's six-step modified framework has been developed to address this synthesis gap. It aims to systematically map the empirical literature that has investigated online suicidal thoughts and/or behaviours talk. It is anticipated that review outcomes could inform the training of health practitioners and peer/professional online moderators in how to best talk with people experiencing suicidal thoughts and/or behaviours. Outcomes could also form an evidence-base for developing policies and practices that focus on online places as safe spaces to talk about suicidal thoughts and/or behaviours. Developers of safe language guidelines could also use the outcomes to audit how well current guidelines reflect empirical evidence. Outcomes could enable researchers to design future online suicidal thoughts and/behaviours talk studies that extend our understandings of suicide leading to potential refinements of contemporary suicide theories/models.

There are limited data describing SARS-CoV-2-specific immune responses and their durability following infection and vaccination in nursing home residents. We conducted a prospective longitudinal evaluation of 11 consenting SARS-CoV-2-positive nursing home residents to evaluate the quantitative titers and durability of binding antibodies detected after SARS-CoV-2 infection and subsequent COVID-19 vaccination. The evaluation included nine visits over 150 days from October 25, 2020, through April 1, 2021. Visits included questionnaire administration, blood collection for serology, and paired anterior nasal specimen collection for testing by BinaxNOW™ COVID-19 Ag Card (BinaxNOW), reverse transcription polymerase chain reaction (RT-PCR), and viral culture. We evaluated quantitative titers of binding SARS-CoV-2 antibodies post-infection and post-vaccination (beginning after the first dose of the primary series). The median age among participants was 74 years; one participant was immunocompromised. Of 10 participants with post-infection serology results, 9 (90%) had detectable Pan-Ig, IgG, and IgA antibodies, and 8 (80%) had detectable IgM antibodies. At first antibody detection post-infection, two-thirds (6/9, 67%) of participants were RT-PCR-positive, but none were culture- positive. Ten participants received vaccination; all had detectable Pan-Ig, IgG, and IgA antibodies through their final observation ≤90 days post-first dose. Post-vaccination geometric means of IgG titers were 10-200-fold higher than post-infection. Nursing home residents in this cohort mounted robust immune responses to SARS-CoV-2 post-infection and post-vaccination. The augmented antibody responses post-vaccination are potential indicators of enhanced protection that vaccination may confer on previously infected nursing home residents.

Successful recruitment of invertebrate larvae to reef substrates is essential to the health of tropical coral reef ecosystems and to their capacity to recover from disturbances. Crustose calcifying red algae (CCRA) are a species rich group of seaweeds that have been identified as important recruitment substrates for scleractinian corals. Most studies on the settlement preference of coral larvae on CCRA use morphological species identifications that can lead to unreliable species identification and do not allow for examining species-specific interactions between coral larvae and CCRA. Accurate identifications of CCRA species is important for coral reef restoration and management to assess CCRA community composition and to detect CCRA species that are favored as coral recruitment substrates. In this study, DNA sequence analysis, was used to identify CCRA species to (1) investigate the species richness and community composition of CCRA on experimental coral recruitment tiles and (2) assess if the coral Acropora surculosa preferred any of these CCRA species as recruitment substrates. The CCRA community assemblages on the coral recruitment tiles was species-rich, comprising 27 distinct CCRA species of the orders Corallinales and Peyssonneliales which constitute new species records for Guam. Lithophylloideae sp. 1 (Corallinales) was the CCRA species that was significantly favored by coral larvae as a recruitment substrate. Lithophylloideae sp. 1 showed to hold a valuable ecological role for coral larval recruitment preference. Lithophylloideae sp. 1 had the highest benthic cover on the recruitment tiles and contained most A. surculosa recruits. DNA barcoding revealed a high taxonomic diversity of CCRA species on a microhabitat scale and provided detailed insight into the species-specific ecological interactions between CCRA and corals. With a steady decline in coral cover, detailed information on species interactions that drive reef recovery is valuable for the planning of marine management actions and restoration efforts.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the coronavirus disease-19 (COVID-19) pandemic, was identified in late 2019 and caused >5 million deaths by February 2022. To date, targeted antiviral interventions against COVID-19 are limited. The spectrum of SARS-CoV-2 infection ranges from asymptomatic to fatal disease. However, the reasons for varying outcomes to SARS-CoV-2 infection are yet to be elucidated. Here we show that an endogenously activated interferon lambda (IFNλ1) pathway leads to resistance against SARS-CoV-2 infection. Using a well-differentiated primary nasal epithelial cell (WD-PNEC) culture model derived from multiple adult donors, we discovered that susceptibility to SARS-CoV-2 infection, but not respiratory syncytial virus (RSV) infection, varied. One of four donors was resistant to SARS-CoV-2 infection. High baseline IFNλ1 expression levels and associated interferon stimulated genes correlated with resistance to SARS-CoV-2 infection. Inhibition of the JAK/STAT pathway in WD-PNECs with high endogenous IFNλ1 secretion resulted in higher SARS-CoV-2 titres. Conversely, prophylactic IFNλ treatment of WD-PNECs susceptible to infection resulted in reduced viral titres. An endogenously activated IFNλ response, possibly due to genetic differences, may be one explanation for the differences in susceptibility to SARS-CoV-2 infection in humans. Importantly, our work supports the continued exploration of IFNλ as a potential pharmaceutical against SARS-CoV-2 infection.

Lipoedema is a chronic adipose tissue disorder mainly affecting women, causing excess subcutaneous fat deposition on the lower limbs with pain and tenderness. There is often a family history of lipoedema, suggesting a genetic origin, but the contribution of genetics is currently unclear. A tightly phenotyped cohort of 200 lipoedema patients was recruited from two UK specialist clinics. Objective clinical characteristics and measures of quality of life data were obtained. In an attempt to understand the genetic architecture of the disease better, genome-wide single nucleotide polymorphism (SNP) genotype data were obtained, and a genome wide association study (GWAS) was performed on 130 of the recruits. The analysis revealed genetic loci suggestively associated with the lipoedema phenotype, with further support provided by an independent cohort taken from the 100,000 Genomes Project. The top SNP rs1409440 (ORmeta ≈ 2.01, Pmeta ≈ 4 x 10–6) is located upstream of LHFPL6, which is thought to be involved with lipoma formation. Exactly how this relates to lipoedema is not yet understood. This first GWAS of a UK lipoedema cohort has identified genetic regions of suggestive association with the disease. Further replication of these findings in different populations is warranted.

Understanding the genomic architecture and molecular mechanisms of cognitive functioning in healthy individuals is critical for developing tailored interventions to enhance cognitive functioning, as well as for identifying targets for treating impaired cognition. There has been substantial progress in uncovering the genetic composition of the general cognitive ability (g). However, there is an ongoing debate whether executive functioning (EF)-another key predictor of cognitive health and performance, is separable from general g. To provide an analytical review on existing findings on genetic influences on the relationship between g and EF, we re-analysed a subset of genome-wide association studies (GWAS) from the GWAS catalogue that used measures of g and EF as outcomes in non-clinical populations. We identified two sets of single nucleotide polymorphisms (SNPs) associated with g (1,372 SNPs across 12 studies), and EF (300 SNPs across 5 studies) at p

Pneumococcal conjugate vaccines reduce the burden of invasive pneumococcal disease, but the sustained effect of these vaccines can be diminished by an increase in disease caused by non-vaccine serotypes. To describe pneumococcal serotype epidemiology in Botswana following introduction of 13-valent pneumococcal conjugate vaccine (PCV-13) in July 2012, we performed molecular serotyping of 268 pneumococcal strains isolated from 221 children between 2012 and 2017. The median (interquartile range) age of the children included in this analysis was 6 (3,12) months. Fifty-nine percent of the children had received at least one dose of PCV-13 and 35% were fully vaccinated with PCV-13. While colonization by vaccine serotypes steadily declined following PCV-13 introduction, 25% of strains isolated more than 3 years after vaccine introduction were PCV-13 serotypes. We also observed an increase in colonization by non-vaccine serotypes 21 and 23B, which have been associated with invasive pneumococcal disease and antibiotic resistance in other settings.

To reach its goal of ending AIDS by 2030, Thailand has adopted antiretroviral treatment as prevention and HIV pre-exposure prophylaxis for men who have sex with men (MSM) and transgender women (TGW) as its core HIV control strategy. However, in the absence of reliable epidemiologic indicators, the impact of these policies on the course of the HIV epidemic in these groups remains unknown. To help answer this question, we formulated an HIV epidemic consensus initiative for Bangkok, Thailand, to analyze epidemiologic and program data and reach agreement between experts and stakeholders on the evolving state of the HIV epidemic among MSM and TGW. A customized Delphi process was used to consult and consolidate viewpoints of experts and stakeholders. Experts presented and discussed HIV prevalence and incidence data from recent and ongoing studies among MSM and TGW in Bangkok (2014 to 2018) during a meeting with stakeholders representing government, donors, and civil society. Agreement about the course of the HIV epidemic among MSM and TGW was attained by voting consensus. Based on presented data, meeting participants agreed that HIV prevalence and incidence had decreased among Bangkok MSM from 2014 to 2018. Despite these declines, HIV prevalence and incidence were found to remain high. This was particularly the case among younger MSM. Participants agreed that there was no evidence for a decrease in HIV prevalence and incidence among Bangkok TGW. Introduction of antiretroviral treatment as prevention and HIV pre-exposure prophylaxis may have contributed to these declines. However, HIV prevalence and incidence remained high, and no signs of a decrease were reported among Bangkok TGW. At the current rate of new HIV infections in MSM and TGW, Thailand will not reach its goal of ending AIDS by 2030. This HIV consensus initiative may serve as a model for building agreement and advocacy on epidemiologic and program data and their implications for a large metropolitan city.

Progressive immune deficiency of aging is characterized by severe thymic atrophy, contracted T cell repertoire, and poor immune function. p63 is critical for the proliferative potential of embryonic and adult stem cells, as well as thymic epithelial cells (TECs). Because p63 null mice experience rapid post-natal lethality due to epidermal and limb morphogenesis defects, studies to define a role for p63 expression in TEC biology focused on embryonic thymus development and in vitro experiments. Since post-natal thymic stromal development and function differs from that of the embryo, we assessed the impact of lineage-restricted p63 loss on pre- and post-natal murine TEC function by generating mice with a loss of p63 function targeted to TEC, termed p63TECko mice. In adult p63TECko mice, severe thymic hypoplasia was observed with a lack in a discernable segregation into medullary and cortical compartments and peripheral T cell lymphopenia. This profound thymic defect was seen in both neonatal as well as embryonic p63TECko mice. In addition to TECs, p63 also plays in important role in the development of stratified epithelium of the skin; lack of p63 results in defects in skin epidermal stratification and differentiation. Interestingly, all adult p63TECko mice lacked hair follicles despite having normal p63 expression in the skin. Together our results show a critical role of TEC p63 in thymic development and maintenance and show that p63 expression is critical for hair follicle formation.

Introduction Voluntary medical male circumcision (VMMC) uptake has been slow in some countries, including Botswana. To inform demand creation efforts, we examined sociodemographic characteristics and referral procedures associated with VMMC uptake in the Botswana Combination Prevention Project (BCPP) and examined the effectiveness of referral of men to MC services from HIV testing venues. Design BCPP was a community-randomized trial evaluating the impact of a combination HIV prevention package which included VMMC on community HIV incidence. We conducted a sub-analysis of VMMC uptake in intervention communities. Methods During the initial VMMC campaign in 15 intervention communities, baseline male circumcision (MC) status was assessed among men eligible for HIV testing. Uncircumcised male community residents aged 16–49 years with negative/unknown HIV status were mobilized and linked to study VMMC services. Outcomes included MC baseline status and uptake through study services. Univariate and multivariate logistic regressions were performed to identify factors associated with MC uptake. Results Of 12,864 men eligible for testing, 50% (n = 6,448) were already circumcised. Among the uncircumcised men (n = 6,416), 10% (n = 635) underwent MC. Of the 5,071 men identified as eligible for MC through HIV testing services, 78% declined referral and less than 1% of those were circumcised. Of those accepting referral (n = 1,107), 16% were circumcised. Younger (16–24 years) (aOR: 1.51; 95%CI:1.22,1.85), unemployed men (aOR:1.34; 95%CI: 1.06,1.69), and those undergoing HIV testing at mobile venues (aOR: 1.88; 95%CI: 1.53,2.31) were more likely to get circumcised. Fear of pain was the most prevalent (27%) reason given for not being circumcised. Conclusion Younger, unemployed men seeking HIV testing at mobile sites in Botswana were more likely to get VMMC. Addressing unique barriers for employed and older men may be necessary. Given the simplicity of VMMC as an intervention, the HIV testing programs offer a platform for identifying uncircumcised men and offering information and encouragement to access services.

Introduction There have been more than 425 million COVID-19 infections worldwide. Post-COVID illness has become a common, disabling complication of this infection. Therefore, it presents a significant challenge to global public health and economic activity. Methods Comprehensive clinical assessment (symptoms, WHO performance status, cognitive testing, CPET, lung function, high-resolution CT chest, CT pulmonary angiogram and cardiac MRI) of previously well, working-age adults in full-time employment was conducted to identify physical and neurocognitive deficits in those with severe or prolonged COVID-19 illness. Results 205 consecutive patients, age 39 (IQR30.0–46.7) years, 84% male, were assessed 24 (IQR17.1–34.0) weeks after acute illness. 69% reported ≥3 ongoing symptoms. Shortness of breath (61%), fatigue (54%) and cognitive problems (47%) were the most frequent symptoms, 17% met criteria for anxiety and 24% depression. 67% remained below pre-COVID performance status at 24 weeks. One third of lung function tests were abnormal, (reduced lung volume and transfer factor, and obstructive spirometry). HRCT lung was clinically indicated in Conclusion Despite low rates of residual cardiopulmonary pathology, in this cohort, with low rates of premorbid illness, there is a high burden of symptoms and failure to regain pre-COVID performance 6-months after acute illness. Cognitive assessment identified a specific deficit of the same magnitude as intoxication at the UK drink driving limit or the deterioration expected with 10 years ageing, which appears to contribute significantly to the symptomatology of long-COVID.

Studying land use change in protected areas (PAs) located in tropical forests is a major conservation priority due to high conservation value (e.g., species richness and carbon storage) here, coupled with generally high deforestation rates. Land use change researchers use a variety of land cover products to track deforestation trends, including maps they produce themselves and readily available products, such as the Global Forest Change (GFC) dataset. However, all land cover maps should be critically assessed for limitations and biases to accurately communicate and interpret results. In this study, we assess deforestation in PA complexes located in agricultural frontiers in the Amazon Basin. We studied three specific sites: Amboró and Carrasco National Parks in Bolivia, Jamanxim National Forest in Brazil, and Tambopata National Reserve and Bahuaja-Sonene National Park in Peru. Within and in 20km buffer areas around each complex, we generated land cover maps using composites of Landsat imagery and supervised classification, and compared deforestation trends to data from the GFC dataset. We then performed a dissimilarity analysis to explore the discrepancies between the two remote sensing products. Both the GFC and our supervised classification showed that deforestation rates were higher in the 20km buffer than inside the PAs and that Jamanxim National Forest had the highest deforestation rate of the PAs we studied. However, GFC maps showed consistently higher rates of deforestation than our maps. Through a dissimilarity analysis, we found that many of the inconsistencies between these datasets arise from different treatment of mixed pixels or different parameters in map creation (for example, GFC does not detect reforestation after 2012). We found that our maps underestimated deforestation while GFC overestimated deforestation, and that true deforestation rates likely fall between our two estimates. We encourage users to consider limitations and biases when using or interpreting our maps, which we make publicly available, and GFC's maps.

PurposeLesbian, gay, bisexual, transgender, and queer (LGBTQ) individuals experience high rates of adverse mental health outcomes due to the stressors they experience in families, communities, and society more broadly. Work and workplaces have the potential to influence these outcomes given their ability to amplify minority stress, and their ability to influence social and economic wellbeing in this already marginalized population. This study aims to identify how sociodemographic characteristics and characteristics of work, including degree of precarity, industry and perceived workplace support for LGBTQ people, influence self-reported mental health among LGBTQ people in two Canadian cities.MethodsSelf-identified LGBTQ workers ≥16 years of age (n = 531) in Sudbury and Windsor, Ontario, Canada were given an online survey between July 6 and December 2, 2018. Multivariate ordinal logistic regression was used to calculate odds ratios (OR) to evaluate differences in gender identity, age, income, industry, social precarity, work environment, and substance use among workers who self-reported very poor, poor, or neutral mental health, compared with a referent group that self-reported good or very good mental health on a five-point Likert scale about general mental health.ResultsLGBTQ workers with poor or neutral mental health had greater odds of: being cisgender women or trans compared with being cisgender men; being aged ConclusionsBoth precarious work and unsupportive work environments contribute to poor mental health among LGBTQ people. These factors are compounded for trans workers who face poorer mental health than cis-LGBQ workers in similar environments.

BackgroundThe high-sensitivity cardiac troponin on presentation to rule out myocardial infarction (HiSTORIC) study was a stepped-wedge cluster randomised trial with long before-and-after periods, involving seven hospitals across Scotland. Results were divergent for the binary safety endpoint (type 1 or type 4b myocardial infarction or cardiac death) across certain pre-specified analyses, which warranted further investigation. In particular, the calendar-matched analysis produced an odds ratio in the opposite direction to the primary logistic mixed-effects model analysis.MethodsSeveral post-hoc statistical models were fitted to each of the co-primary outcomes of length of hospital stay and safety events, which included adjusting for exposure time, incorporating splines, and fitting a random time effect. We improved control of patient characteristics over time by adjusting for multiple additional covariates using different methods: direct inclusion, regression adjustment for propensity score, and weighting. A data augmentation approach was also conducted aiming to reduce the effect of sparse data bias. Finally, the raw data was examined.ResultsThe new statistical models confirmed the results of the pre-specified trial analysis. In particular, the observed divergence between the calendar-matched and other analyses remained, even after performing the covariate adjustment methods, and after using data augmentation. Divergence was particularly acute for the safety endpoint, which had an event rate of 0.36% overall. Examining the raw data was particularly helpful to assess the sensitivity of the results to small changes in event rates and identify patterns in the data.ConclusionsOur experience reveals the importance of conducting multiple pre-specified sensitivity analyses and examining the raw data, particularly for stepped wedge trials with low event rates or with a small number of sites. Before-and-after analytical approaches that adjust for differences in patient populations but avoid direct modelling of the time trend should be considered in future stepped wedge trials with similar designs.

Surface waters, especially those receiving wastewater flows, can disseminate antimicrobial resistant bacteria (ARB), antimicrobial resistance genes (ARG), and antibiotics. In the Scioto River of central Ohio, United States, we evaluated fishes as potential sentinels of ARB and antimicrobial contamination and investigated the influence of antimicrobial exposure on the fish intestinal resistome. Seventy-seven fish were collected from river reaches receiving inputs from two wastewater treatment plants that serve the greater Columbus Metropolitan Area. Fish were screened for the presence of cephalosporin-resistant (CeRO) and carbapenem-resistant (CRO) organisms, epidemic carbapenemase genes, and antibiotic drugs and metabolites using culture methods, droplet digital PCR, and ultra-high performance liquid chromatography tandem mass spectroscopy (UHPLC-MS/MS). Nearly 21% of fish harbored a CeRO in their resistome, with 19.4% exhibiting bacteria expressing an AmpC genotype encoded by blaCMY, and 7.7% with bacteria expressing an extended-spectrum β-lactamase phenotype encoded by blaCTX-M. blaKPC and blaNDM were present in 87.7% (57/65) and 80.4% (37/46) of the intestinal samples at an average abundance of 104 copies. Three antibiotics-lincomycin (19.5%), azithromycin (31.2%) and sulfamethoxazole (3.9%)-were found in hepatic samples at average concentrations between 25-31 ng/g. Fish harboring blaCTX-M and those exposed to azithromycin were at greater odds of being downstream of a wastewater treatment plant. Fish that bioconcentrated antibiotics in their liver were not at greater odds of harboring CeRO, CRO, or epidemic carbapenemase gene copies in their resistome. Our findings confirm that fishes can be effective bioindicators of surface waters contaminated with ARB, ARG, and antibiotics. Moreover, our findings highlight the varying importance of different mechanisms that facilitate establishment of ARB in aquatic ecosystems.

Fiber intake may be associated with lower risk of metabolic syndrome (MetS) but data from metabolically unhealthy African American women is sparse. We examined the association of dietary fiber intake and MetS among postmenopausal African American women with obesity. Baseline cross-sectional data from the Focused Intervention on Exercise to Reduce CancEr (FIERCE) trial of 213 women (mean age 58.3 years) were used. Dietary intake was assessed by Food Frequency Questionnaires (FFQs). Multivariate linear and logistic regressions were performed to estimate associations of MetS with fiber intake and adherence to dietary fiber intake guidelines, respectively. Mean daily fiber intake was (10.33 g/1000kcal) in women with impaired metabolic health. We observed an inverse association of total fiber intake with MetS. One unit increase in energy-adjusted fiber intake was associated with a 0.10 unit decrease in the MetS z-score (p = 0.02). Similar results were obtained for both soluble and insoluble fiber. In multivariate-adjusted analyses, participants not adherent to fiber intake recommendations were more likely to have MetS as compared to those reporting intakes in the recommended range (adjusted odds ratio 4.24, 95% CI: 1.75, 10.30). Of the MetS components, high fasting glucose and high triglycerides were all associated with lower intake of fiber. Study participants who consumed a higher amount of fiber had a better overall metabolic profile and were less likely to have MetS in our cross-sectional analysis of postmenopausal African American women with obesity and unhealthy metabolic profiles.

Studies have outlined the negative consequences of the COVID-19 pandemic to psychological health. However, the potential within-individual diversity of experiences during COVID-19, and how such experiences relate to indices of psychological distress and COVID-19-specific stressors, remains to be explored. A large online sample of American MTurk Workers (N = 3,731; Mage = 39.54 years, SD = 13.12; 51.70% female) completed short assessments of psychological distress, COVID-19-specific stressors (e.g., wage loss, death), and seven items assessing negative and positive COVID-19 experiences. Latent profile analyses were used to identify underlying profiles of COVID-19 experiences. A four-profile solution was retained representing profiles that were: (1) predominantly positive (n = 839; 22.49%), (2) predominantly negative (n = 849; 22.76%), (3) moderately mixed (n = 1,748; 46.85%), and (4) high mixed (n = 295; 7.91%). The predominantly positive profile was associated with lower psychological distress, whereas both the predominantly negative and high mixed profiles were associated with higher psychological distress. Interestingly, specific COVID-19 stressful events were associated with the high mixed profile. The present study challenges the narrative that the impacts of COVID-19 have been unilaterally negative. Future directions for research are proposed.

Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) is used worldwide to test and trace the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). "Extraction-less" or "direct" real time-reverse transcription polymerase chain reaction (RT-PCR) is a transparent and accessible qualitative method for SARS-CoV-2 detection from nasopharyngeal or oral pharyngeal samples with the potential to generate actionable data more quickly, at a lower cost, and with fewer experimental resources than full RT-qPCR. This study engaged 10 global testing sites, including laboratories currently experiencing testing limitations due to reagent or equipment shortages, in an international interlaboratory ring trial. Participating laboratories were provided a common protocol, common reagents, aliquots of identical pooled clinical samples, and purified nucleic acids and used their existing in-house equipment. We observed 100% concordance across laboratories in the correct identification of all positive and negative samples, with highly similar cycle threshold values. The test also performed well when applied to locally collected patient nasopharyngeal samples, provided the viral transport media did not contain charcoal or guanidine, both of which appeared to potently inhibit the RT-PCR reaction. Our results suggest that direct RT-PCR assay methods can be clearly translated across sites utilizing readily available equipment and expertise and are thus a feasible option for more efficient COVID-19 coronavirus disease testing as demanded by the continuing pandemic.

Epidemiological studies suggest a relationship between blood lipids and immune-mediated diseases, but the nature of these associations is not well understood. We used genome-wide association studies (GWAS) to investigate shared single nucleotide polymorphisms (SNPs) between blood lipids and immune-mediated diseases. We analyzed data from GWAS (n~200,000 individuals), applying new False Discovery Rate (FDR) methods, to investigate genetic overlap between blood lipid levels [triglycerides (TG), low density lipoproteins (LDL), high density lipoproteins (HDL)] and a selection of archetypal immune-mediated diseases (Crohn's disease, ulcerative colitis, rheumatoid arthritis, type 1 diabetes, celiac disease, psoriasis and sarcoidosis). We found significant polygenic pleiotropy between the blood lipids and all the investigated immune-mediated diseases. We discovered several shared risk loci between the immune-mediated diseases and TG (n = 88), LDL (n = 87) and HDL (n = 52). Three-way analyses differentiated the pattern of pleiotropy among the immune-mediated diseases. The new pleiotropic loci increased the number of functional gene network nodes representing blood lipid loci by 40%. Pathway analyses implicated several novel shared mechanisms for immune pathogenesis and lipid biology, including glycosphingolipid synthesis (e.g. FUT2) and intestinal host-microbe interactions (e.g. ATG16L1). We demonstrate a shared genetic basis for blood lipids and immune-mediated diseases independent of environmental factors. Our findings provide novel mechanistic insights into dyslipidemia and immune-mediated diseases and may have implications for therapeutic trials involving lipid-lowering and anti-inflammatory agents.

BackgroundLow/ered cholesterol is linked to aggression in some study designs. Cases/series have reported reproducible aggression increases on statins, but statins also bear mechanisms that could reduce aggression. Usual statin effects on aggression have not been characterized.Methods1016 adults (692 men, 324 postmenopausal women) underwent double-blind sex-stratified randomization to placebo, simvastatin 20mg, or pravastatin 40mg (6 months). The Overt-Aggression-Scale-Modified-Aggression-Subscale (OASMa) assessed behavioral aggression. A significant sex-statin interaction was deemed to dictate sex-stratified analysis. Exploratory analyses assessed the influence of baseline-aggression, testosterone-change (men), sleep and age.ResultsThe sex-statin interaction was significant (P=0.008). In men, statins tended to decrease aggression, significantly so on pravastatin: difference=-1.0(SE=0.49)P=0.038. Three marked outliers (OASMa-change ≥40 points) offset otherwise strong significance-vs-placebo: statins:-1.3(SE=0.38)P=0.0007; simvastatin:-1.4(SE=0.43)P=0.0011; pravastatin:-1.2(SE=0.45)P=0.0083. Age≤40 predicted greater aggression-decline on statins: difference=-1.4(SE=0.64)P=0.026. Aggression-protection was emphasized in those with low baseline aggression: age

Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity.

The genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the world's population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians.