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Background: The large language model ChatGPT can now accept image input with the GPT4-vision (GPT4V) version. We aimed to compare the performance of GPT4V to pretrained U-Net and vision transformer (ViT) models for the identification of the progression of multiple sclerosis (MS) on magnetic resonance imaging (MRI). Methods: Paired coregistered MR images with and without progression were provided as input to ChatGPT4V in a zero-shot experiment to identify radiologic progression. Its performance was compared to pretrained U-Net and ViT models. Accuracy was the primary evaluation metric and 95% confidence interval (CIs) were calculated by bootstrapping. We included 170 patients with MS (50 males, 120 females), aged 21–74 years (mean 42.3), imaged at a single institution from 2019 to 2021, each with 2–5 MRI studies (496 in total). Results: One hundred seventy patients were included, 110 for training, 30 for tuning, and 30 for testing; 100 unseen paired images were randomly selected from the test set for evaluation. Both U-Net and ViT had 94% (95% CI: 89–98%) accuracy while GPT4V had 85% (77–91%). GPT4V gave cautious nonanswers in six cases. GPT4V had precision (specificity), recall (sensitivity), and F1 score of 89% (75–93%), 92% (82–98%), 91 (82–97%) compared to 100% (100–100%), 88 (78–96%), and 0.94 (88–98%) for U-Net and 94% (87–100%), 94 (88–100%), and 94 (89–98%) for ViT. Conclusion: The performance of GPT4V combined with its accessibility suggests has the potential to impact AI radiology research. However, misclassified cases and overly cautious non-answers confirm that it is not yet ready for clinical use. Relevance statement: GPT4V can identify the radiologic progression of MS in a simplified experimental setting. However, GPT4V is not a medical device, and its widespread availability highlights the need for caution and education for lay users, especially those with limited access to expert healthcare. Key Points: Without fine-tuning or the need for prior coding experience, GPT4V can perform a zero-shot radiologic change detection task with reasonable accuracy. However, in absolute terms, in a simplified "spot the difference" medical imaging task, GPT4V was inferior to state-of-the-art computer vision methods. GPT4V's performance metrics were more similar to the ViT than the U-net. This is an exploratory experimental study and GPT4V is not intended for use as a medical device. [ABSTRACT FROM AUTHOR]

Background: The rapidly changing policy climate related to cannabis legalization has led to drastic changes in cannabis use in the United States (US). Medical cannabis use is increasing overall, but at a faster rate among older adults compared to other age groups. Objective: The aim was to investigate older adults' cannabis use behaviors and attitudes around disclosing medical cannabis use to their primary healthcare providers (HCPs). Methods: Nineteen older adults (ages 65+ years) with self-reported medical cannabis use were recruited from flyers posted in ambulatory clinics in San Diego, CA. Surveys and semi-structured interviews on cannabis use were completed. A multi-methods approach was used to analyze data. Results: Participants' mean age was 75.3 years; 52.6% identified as women, and 89.5% as White. Cannabis was used by all participants to treat pain and by 75% for insomnia, with 25–33% reductions in use of prescription medications to treat these symptoms. Approximately 89% reported their primary HCPs were aware of their cannabis use, and 84.2% felt very comfortable/comfortable talking to HCPs about cannabis. Common themes from interviews included participants (1) being motivated to disclose cannabis use to their HCPs to seek medical advice on dosing, side effects, and benefits of cannabis, (2) feeling comfortable disclosing cannabis use as legalization has eased the stigma around cannabis use, and (3) perceiving mostly neutral attitudes from HCPs on their cannabis use. Conclusion: The study emphasizes the pivotal role of HCPs as educators in addressing patient inquiries about cannabis, underlining the need for equipping healthcare professionals with evidence-based knowledge through education and training initiatives. [ABSTRACT FROM AUTHOR]

Aims: We examined whether admission risk increases at a certain threshold of number of systems medicated or whether any increase confers greater admission risk in either sex in a community-dwelling cohort of older persons in Hertfordshire. This study uses a longitudinal retrospective study design. Methods: Data from 2997 men and women (aged 59–73 at baseline) were analyzed. Participants were followed up from baseline (1998–2004) until December 2018 using Hospital Episode Statistics and mortality data, reporting clinical outcomes using ICD-10 coding. Number of systems medicated in relation to mortality (all-cause, cancer-related, cardiovascular-related) and admission (any, neurological, cardiovascular, and respiratory) were examined using Cox regression. Results: Apart from cancer-related mortality among women, more systems medicated predicted increased risk of all events among both sexes (p ≤ 0.001). For 'any', cardiovascular and respiratory admissions, there were increases in risk for each category of number of systems medicated. For example, compared to men with no systems medicated, those with 1, 2 and > 2 systems medicated had hazard ratios (95% CI) for cardiovascular admissions of 1.82 (1.57,2.12), 2.39 (2.00,2.84) and 3.45 (2.84,4.20) respectively; estimates among women were 1.74 (1.44,2.11), 2.35 (1.92,2.88) and 3.40 (2.79,4.13). Conclusions: Increases in numbers of systems medicated conferred greater risk of admission in both sexes. Interventions aimed at reducing the burden of chronic disease in mid-late adulthood are required. [ABSTRACT FROM AUTHOR]

Background: Multi-ligament Knee Injuries (MLKI) are often caused by a high-energy impact resulting in dislocation of the knee joint. Given the higher degree of instability associated with these MLKIs, surgical fixation with adjunctive internal bracing and the use of suture augmentation have been proposed with the intention of better restoring knee stability and improving the long-term outcomes of surgery. This systematic review seeks to appraise the current literature in relation to the role of internal bracing in the management of MLKI. Methods: All randomised control trials, observational studies, cohort studies, and cross-sectional studies containing patients with multi-ligamentous knee injuries managed with the use of internal bracing or suture tape augmentation were included in this review. The primary outcomes of interest were re-operation and failure rates, with secondary outcomes focussed on patient-reported outcome measures (PROMs) and examination findings of knee stability. Results: 282 studies were identified for screening, 13 of which were suitable for inclusion and five of these had injuries with Schenck grade III or above. Of the studies identified, failure rates ranged from 0 to 13.6%. Lysholm score was the most commonly utilised PROM tool with scores ranging from 61.8 to 95. Stiffness requiring MUA ± adhesiolysis was a common complication identified across studies. Conclusions: The use of internal bracing in Multi-ligament Knee Injuries appears to be as effective as not using an internal bracing technique. The post-operative PROMs and relatively low failure rates reflect promising outcomes for the ongoing use of internal bracing in MLKI. However, further prospective studies directly comparing braced versus non-braced ligamentous repairs are required in order to definitively determine if the use of the internal brace does allow for increased joint stability and early rehabilitation. [ABSTRACT FROM AUTHOR]

The Drift Prairie, in central North America, has been largely converted from grasslands to croplands, but still contains thousands of wetlands used by shorebirds and waterfowl during breeding and migration periods. Consequently, many of the remaining wetlands are situated within cropland where disturbance regimes (i.e., fire, grazing, and water-level dynamics), which occurred naturally prior to agricultural development, have been highly altered by landscape fragmentation from agriculture practices. Currently, smaller wetlands within crop fields are subject to disturbances stemming from agricultural practices (i.e., manipulations), such as burning, disking, harvesting, and mowing. We evaluated vegetation structure of idled (i.e., not recently manipulated by farming practices) and manipulated agricultural wetlands to investigate whether management method or resulting vegetation structure had greater influence on occurrence probabilities and densities of dabbling ducks and shorebirds during spring. All manipulation methods reduced vegetation heights compared to idled wetlands and most manipulations reduced the proportion of vegetation cover in inundated areas. Wetland manipulations generally increased shorebird occurrence compared to idled wetlands, whereas vegetation variables better explained duck occurrence probabilities. Duck occurrence peaked in wetlands with lower vegetation coverage (32%), and duck densities decreased as vegetation coverage increased beyond 10%. While more studies are needed to understand underlying mechanisms driving these outcomes, our results indicate that including periodic disturbances that reduce dense vegetation within wetlands in agricultural fields would increase their use by migrating and breeding shorebirds and dabbling ducks. [ABSTRACT FROM AUTHOR]

Aim: Code-free deep learning (CFDL) allows clinicians without coding expertise to build high-quality artificial intelligence (AI) models without writing code. In this review, we comprehensively review the advantages that CFDL offers over bespoke expert-designed deep learning (DL). As exemplars, we use the following tasks: (1) diabetic retinopathy screening, (2) retinal multi-disease classification, (3) surgical video classification, (4) oculomics and (5) resource management. Methods: We performed a search for studies reporting CFDL applications in ophthalmology in MEDLINE (through PubMed) from inception to June 25, 2023, using the keywords 'autoML' AND 'ophthalmology'. After identifying 5 CFDL studies looking at our target tasks, we performed a subsequent search to find corresponding bespoke DL studies focused on the same tasks. Only English-written articles with full text available were included. Reviews, editorials, protocols and case reports or case series were excluded. We identified ten relevant studies for this review. Results: Overall, studies were optimistic towards CFDL's advantages over bespoke DL in the five ophthalmological tasks. However, much of such discussions were identified to be mono-dimensional and had wide applicability gaps. High-quality assessment of better CFDL applicability over bespoke DL warrants a context-specific, weighted assessment of clinician intent, patient acceptance and cost-effectiveness. We conclude that CFDL and bespoke DL are unique in their own assets and are irreplaceable with each other. Their benefits are differentially valued on a case-to-case basis. Future studies are warranted to perform a multidimensional analysis of both techniques and to improve limitations of suboptimal dataset quality, poor applicability implications and non-regulated study designs. Conclusion: For clinicians without DL expertise and easy access to AI experts, CFDL allows the prototyping of novel clinical AI systems. CFDL models concert with bespoke models, depending on the task at hand. A multidimensional, weighted evaluation of the factors involved in the implementation of those models for a designated task is warranted. [ABSTRACT FROM AUTHOR]

Kelp forests have deteriorated globally due to anthropogenic stressors. There is an urgent need to extend baselines, to understand the processes that underlie the persistence and recovery of kelp forests, and to distinguish the normal range of ecosystem variability from more extreme changes. Using a mixed-method, historical ecology approach, we integrate archival data, oral histories, and contemporary ecological data to examine the dynamics of kelp forests over a multi-decadal to multi-century time-period in central California. We focus on sea otters, sunflower seastars, sea urchins, kelp cover, kelp species dynamics, and climate. From 1826 to 2020, kelp was highly variable. There were seven periods of low kelp cover and two periods of exceptionally low kelp cover (1897–1899; 2014–2016) following El Niño-Southern Oscillations (ENSOs). Exceptionally low kelp cover did not occur when two predators—seastars and sea otters—were both present. In all cases, kelp recovered following times of extremely low cover, with a lag, which was extended by the duration of warm water anomalies (ENSO Recovery Lag). Kelp remained low for approximately 2 years following 80% of ENSOs. The greatest kelp decline (12-fold) was in Santa Cruz (northern Monterey Bay). Herbivore populations (sea urchins) were highly variable over the past century and exhibited short- and long-term changes in abundance. Sunflower seastars were present in low, stable abundances prior to seastar wasting disease (1938–2013, mean density = 0.02/m2) when they declined by 97.5%. Insights from this reconstruction indicate that kelp recovery following extended warm water anomalies exhibits a lag and occurs over multiple years. [ABSTRACT FROM AUTHOR]

Purpose: Patients with dihydropyrimidine dehydrogenase (DPD) deficiency are at high risk for severe and fatal toxicity from fluoropyrimidine (FP) chemotherapy. Pre-treatment DPYD testing is standard of care in many countries, but not the United States (US). This survey assessed pre-treatment DPYD testing approaches in the US to identify best practices for broader adoption. Methods: From August to October 2023, a 22-item QualtricsXM survey was sent to institutions and clinicians known to conduct pre-treatment DPYD testing and broadly distributed through relevant organizations and social networks. Responses were analyzed using descriptive analysis. Results: Responses from 24 unique US sites that have implemented pre-treatment DPYD testing or have a detailed implementation plan in place were analyzed. Only 33% of sites ordered DPYD testing for all FP-treated patients; at the remaining sites, patients were tested depending on disease characteristics or clinician preference. Almost 50% of sites depend on individual clinicians to remember to order testing without the assistance of electronic alerts or workflow reminders. DPYD testing was most often conducted by commercial laboratories that tested for at least the four or five DPYD variants considered clinically actionable. Approximately 90% of sites reported receiving results within 10 days of ordering. Conclusion: Implementing DPYD testing into routine clinical practice is feasible and requires a coordinated effort among the healthcare team. These results will be used to develop best practices for the clinical adoption of DPYD testing to prevent severe and fatal toxicity in cancer patients receiving FP chemotherapy. [ABSTRACT FROM AUTHOR]

Mapping spatial variation in stable isotope values (isoscapes) of primary producers and consumers can provide insight into regional patterns of biogeochemistry and be used to trace the movements of mobile animals. Here we present carbon (δ13C) and nitrogen (δ15N) isoscapes for an expansive region of the continental United States (Mid Atlantic Bight to the NW Gulf of Mexico) derived from inshore lizardfish (Synodus foetens) and explore temporal stability and environmental drivers of observed isotopic variation. We observed significant spatial variation in lizardfish δ13C and δ15N values throughout much of the Atlantic and Gulf coasts, reflecting local biogeochemistry regimes. Extensive sampling throughout the northern Gulf of Mexico (NGOM) revealed positive relationships between lizardfish δ13C values and bottom temperature, likely reflecting lower carbon isotope discrimination between CO2 and phytoplankton in highly productive, warm, inshore environments. Conversely, δ15N values were not well explained by environmental parameters, but appeared higher in nearshore environments of the NGOM, which are heavily influenced by nitrogenous run-off from land. An isotopically unique region of high δ13C values and low δ15N values were observed for lizardfish sampled in the Eastern NGOM off the southwest coast of Florida, reflecting a potential influence of seagrass and/or macroalgal productivity supporting the base of the food web. Overall, these findings underscore the utility of benthic lizardfish stable isotopes for inferring local patterns of ocean biogeochemistry throughout expansive ocean environments. In application, these data can be used to define migratory histories of mobile taxa and support contemporary critical habitat assessments. [ABSTRACT FROM AUTHOR]

The Consolidated Standards of Reporting Trials extension for Artificial Intelligence interventions (CONSORT-AI) was published in September 2020. Since its publication, several randomised controlled trials (RCTs) of AI interventions have been published but their completeness and transparency of reporting is unknown. This systematic review assesses the completeness of reporting of AI RCTs following publication of CONSORT-AI and provides a comprehensive summary of RCTs published in recent years. 65 RCTs were identified, mostly conducted in China (37%) and USA (18%). Median concordance with CONSORT-AI reporting was 90% (IQR 77–94%), although only 10 RCTs explicitly reported its use. Several items were consistently under-reported, including algorithm version, accessibility of the AI intervention or code, and references to a study protocol. Only 3 of 52 included journals explicitly endorsed or mandated CONSORT-AI. Despite a generally high concordance amongst recent AI RCTs, some AI-specific considerations remain systematically poorly reported. Further encouragement of CONSORT-AI adoption by journals and funders may enable more complete adoption of the full CONSORT-AI guidelines. The CONSORT-AI extension was developed to provide specific guidance for randomised controlled trials involving Artificial Intelligence (AI) interventions. Here, the authors show that since publication of CONSORT-AI, several AI-specific considerations remain systematically underreported. [ABSTRACT FROM AUTHOR]

Logged and disturbed forests are often viewed as degraded and depauperate environments compared with primary forest. However, they are dynamic ecosystems1 that provide refugia for large amounts of biodiversity2,3, so we cannot afford to underestimate their conservation value4. Here we present empirically defined thresholds for categorizing the conservation value of logged forests, using one of the most comprehensive assessments of taxon responses to habitat degradation in any tropical forest environment. We analysed the impact of logging intensity on the individual occurrence patterns of 1,681 taxa belonging to 86 taxonomic orders and 126 functional groups in Sabah, Malaysia. Our results demonstrate the existence of two conservation-relevant thresholds. First, lightly logged forests (<29% biomass removal) retain high conservation value and a largely intact functional composition, and are therefore likely to recover their pre-logging values if allowed to undergo natural regeneration. Second, the most extreme impacts occur in heavily degraded forests with more than two-thirds (>68%) of their biomass removed, and these are likely to require more expensive measures to recover their biodiversity value. Overall, our data confirm that primary forests are irreplaceable5, but they also reinforce the message that logged forests retain considerable conservation value that should not be overlooked.An analysis of the impact of logging intensity on biodiversity in tropical forests in Sabah, Malaysia, identifies a threshold of tree biomass removal below which logged forests still have conservation value. [ABSTRACT FROM AUTHOR]

Paramos, unique and biodiverse ecosystems found solely in the high mountain regions of the tropics, are under threat. Despite their crucial role as primary water sources and significant carbon repositories in Colombia, they are deteriorating rapidly and garner less attention than other vulnerable ecosystems like the Amazon rainforest. Their fertile soil and unique climate make them prime locations for agriculture and cattle grazing, often coinciding with economically critical deposits such as coal which has led to a steady decline in paramo area. Anthropic impact was evaluated using multispectral images from Landsat and Sentinel over 37 years, on the Guerrero and Rabanal paramos in central Colombia which have experienced rapid expansion of mining and agriculture. Our analysis revealed that since 1984, the Rabanal and Guerrero paramos have lost 47.96% and 59.96% of their native vegetation respectively, replaced primarily by crops, pastures, and planted forests. We detected alterations in the spectral signatures of native vegetation near coal coking ovens, indicating a deterioration of paramo health and potential impact on ecosystem services. Consequently, human activity is reducing the extent of paramos and their efficiency as water sources and carbon sinks, potentially leading to severe regional and even global consequences. [ABSTRACT FROM AUTHOR]

Purpose: One of the challenges for mental health research is the lack of an agreed set of outcome measures that are used routinely and consistently between disciplines and across studies in order to build a more robust evidence base for how to better understand young people's mental health and effectively address diverse needs. Methods: This study involved a scoping review of reviews on consensus of the use of mental health and wellbeing measures with children and young people. We were particularly interested to identify if there are differences in measures that are recommended for children and young people with care experience including those with developmental disabilities. Findings: We identified 41 reviews, of which two had a focus on child welfare settings, three on childhood trauma and 14 focused on children and young people with developmental disabilities. Overall, our review highlights a lack of consensus and a diversity of measures within the field. We identified 60 recommended measures, of which only nine were recommended by more than one review. Conclusions: Our review highlights the need for greater agreement in the use of mental health outcome measures. While our review highlights that there is value in identifying measures that can be used with any child or young person, researchers need to take into account additional considerations when working with children and young people with care experience and those with developmental disabilities, to ensure measures are accessible and sensitive to their life experiences. [ABSTRACT FROM AUTHOR]

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Registry studies have suggested associations between relationship status and fracture risk. We considered associations between relationship status and incident fracture in the Hertfordshire Cohort Study, comprising community-dwelling older adults, and explored associations between socioeconomic and lifestyle factors with relationship status. 2997 participants completed a baseline questionnaire (1998–2004) and clinic visit. Participants were followed up until December 2018 using Hospital Episode Statistics, which report clinical outcomes using codes from the 10th revision of the International Classification of Diseases (ICD-10); these codes were used to ascertain incident fractures. Relationship status (not currently married/cohabiting vs currently married/cohabiting) at baseline was examined in relation to incident fracture using Cox regression. Associations between baseline characteristics and relationship status were examined using logistic regression. Mean baseline age was 66.2 years. 80% were married/cohabiting at baseline; 15% had an incident fracture (mean (SD) follow-up duration: 14.4 (4.5) years). The following were related to greater likelihood of not being married/cohabiting: older age (women only); higher BMI (women only); current smoking; high alcohol consumption (men only); poorer diet quality (men only); lower physical activity; leaving school before age 15 (women only); and not owning one's home. Those not married/cohabiting had greater risk of incident fracture compared to those who were (age-adjusted hazard ratios (95% CI) 1.58 (1.06, 2.38) among men, 1.35 (1.06, 1.72) among women); associations were attenuated after accounting for the above factors associated with relationship status in the corresponding sex. This suggests that differences in health profiles and lifestyle according to relationship status may explain the association between relationship status and fracture risk. [ABSTRACT FROM AUTHOR]

AI-based simulations for educational and assessment purposes are gaining global recognition. Informed by cultural comparison research, this study investigates cross-country variations in users' utilization and perceptions of a simulation-based assessment. Specifically, we conducted a comparative analysis between a sample of South African and Canadian students to uncover potential differences in assessment scores, communication patterns, and reactions vis-a-vis a simulation assessment for evaluating teamwork skills. Data were collected from over 500 undergraduate students in South Africa and Canada who completed a simulation assessment and reported their reactions and perceptions. The findings yielded several noteworthy observations. First, South African students attained higher assessment scores than Canadian students; although, the difference did not quite reach statistical significance at p < 0.05. Second, significant variations were observed in the quantity and style of communication. South African students used fewer words and more polite language, while Canadian students tended to use more decisive language and provided more explanations and help to their virtual teammates. Third, South African students were more likely to perceive their virtual teammates as "human" and were less concerned whether they were real people or virtual. Lastly, compared with their Canadian counterparts, South African students reported more positive reactions and perceived the assessment to be more accurate. These findings warrant further investigation. [ABSTRACT FROM AUTHOR]

Invasions by non-native plant species after fire can negatively affect important ecosystem services and lead to invasion-fire cycles that further degrade ecosystems. The relationship between fire and plant invasion is complex, and the risk of invasion varies greatly between functional types and across geographic scales. Here, we examined patterns and predictors of non-native plant invasion following fire across the western United States. We specifically analyzed how the abundance of non-native plants after fire was related to fire characteristics and environmental conditions, such as climate, soil, and topography, in 26,729 vegetation plots from government networks and individual studies. Non-native plant cover was higher in plots measured after wildfires compared to prescribed burns or unburned plots. The post-fire cover of non-native species varied by plant functional type, and only the cover of short-lived (i.e., annual and biennial) forbs and short-lived C3 grasses was significantly higher in burned plots compared to unburned plots. Cool-season short-lived grasses composed most of the non-native post-fire vegetation, with cheatgrass (Bromus tectorum) being the most recorded species in the dataset. Climate variables were the most influential predictors of the cover of non-native short-lived grasses and forbs after fires, with invasion being more common in areas with drier summers and a higher proportion of yearly precipitation falling in October through March. Models using future projected climate for mid (2041–2070) and end (2071–2100) of century showed a potential for increasing post-fire invasion risk at higher elevations and latitudes. These findings highlight priorities for mitigation, monitoring, and restoration efforts to reduce post-fire plant invasion risk across the western United States. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) has great potential in ophthalmology. We investigated how ambiguous outputs from an AI diagnostic support system (AI-DSS) affected diagnostic responses from optometrists when assessing cases of suspected retinal disease. Thirty optometrists (15 more experienced, 15 less) assessed 30 clinical cases. For ten, participants saw an optical coherence tomography (OCT) scan, basic clinical information and retinal photography (‘no AI’). For another ten, they were also given AI-generated OCT-based probabilistic diagnoses (‘AI diagnosis’); and for ten, both AI-diagnosis and AI-generated OCT segmentations (‘AI diagnosis + segmentation’) were provided. Cases were matched across the three types of presentation and were selected to include 40% ambiguous and 20% incorrect AI outputs. Optometrist diagnostic agreement with the predefined reference standard was lowest for ‘AI diagnosis + segmentation’ (204/300, 68%) compared to ‘AI diagnosis’ (224/300, 75% p = 0.010), and ‘no Al’ (242/300, 81%, p = < 0.001). Agreement with AI diagnosis consistent with the reference standard decreased (174/210 vs 199/210, p = 0.003), but participants trusted the AI more (p = 0.029) with segmentations. Practitioner experience did not affect diagnostic responses (p = 0.24). More experienced participants were more confident (p = 0.012) and trusted the AI less (p = 0.038). Our findings also highlight issues around reference standard definition. [ABSTRACT FROM AUTHOR]

The evidence for the potential of mindfulness-based programmes (MBPs) to support improved stress coping and feelings of burnout in social workers is growing. MBPs which are specifically designed for social workers might help to enhance social work practice, whilst simultaneously supporting reductions in stress, burnout, and attrition in the profession. The aim of this qualitative study was to explore the experience of twelve social workers who completed the Mindfulness-based social work and self-care programme (MBSWSC). Thematic data analysis resulted in six key themes being identified: professional motivation, mindfulness practice challenges and facilitators, benefits of increased self-awareness, impact professionally, use of mindfulness practices in direct work, the importance of having a social work tailored programme. This study provides further promising evidence of the acceptability and effectiveness of MBSWSC as a social work self-care and reflective practice programme. It is becoming increasingly clear that social workers are more likely to enrol in and fully engage with MBPs, which are specifically designed to support their social work practice and stress processing skills, if they are offered by their organisation. The increased access to MBPs of this nature is likely to lead to reduced burnout, and retention issues within the social work profession. [ABSTRACT FROM AUTHOR]

Human-driven extinction threatens entire lineages across the Tree of Life. Here we assess the conservation status of jawed vertebrate evolutionary history, using three policy-relevant approaches. First, we calculate an index of threat to overall evolutionary history, showing that we expect to lose 86-150 billion years (11-19%) of jawed vertebrate evolutionary history over the next 50-500 years. Second, we rank jawed vertebrate species by their EDGE scores to identify the highest priorities for species-focused conservation of evolutionary history, finding that chondrichthyans, ray-finned fish and testudines rank highest of all jawed vertebrates. Third, we assess the conservation status of jawed vertebrate families. We found that species within monotypic families are more likely to be threatened and more likely to be in decline than other species. We provide a baseline for the status of families at risk of extinction to catalyse conservation action. This work continues a trend of highlighting neglected groups-such as testudines, crocodylians, amphibians and chondrichthyans-as conservation priorities from a phylogenetic perspective. [ABSTRACT FROM AUTHOR]

Bioenergetic failure caused by impaired utilisation of glucose and fatty acids contributes to organ dysfunction across multiple tissues in critical illness. Ketone bodies may form an alternative substrate source, but the feasibility and safety of inducing a ketogenic state in physiologically unstable patients is not known. Twenty-nine mechanically ventilated adults with multi-organ failure managed on intensive care units were randomised (Ketogenic n = 14, Control n = 15) into a two-centre pilot open-label trial of ketogenic versus standard enteral feeding. The primary endpoints were assessment of feasibility and safety, recruitment and retention rates and achievement of ketosis and glucose control. Ketogenic feeding was feasible, safe, well tolerated and resulted in ketosis in all patients in the intervention group, with a refusal rate of 4.1% and 82.8% retention. Patients who received ketogenic feeding had fewer hypoglycaemic events (0.0% vs. 1.6%), required less exogenous international units of insulin (0 (Interquartile range 0-16) vs.78 (Interquartile range 0-412) but had slightly more daily episodes of diarrhoea (53.5% vs. 42.9%) over the trial period. Ketogenic feeding was feasible and may be an intervention for addressing bioenergetic failure in critically ill patients. Clinical Trials.gov registration: NCT04101071. Critical illness leads to altered metabolic states and bioenergetic failure caused by impaired utilisation of glucose, fatty acids and amino acids. Here the authors show ketogenic diets may provide a safe and acceptable alternative metabolic fuel enabling energy production and maintaining tissue homeostasis. [ABSTRACT FROM AUTHOR]

Despite decades of genetic studies on late-onset Alzheimer's disease, the underlying molecular mechanisms remain unclear. To better comprehend its complex etiology, we use an integrative approach to build robust predictive (causal) network models using two large human multi-omics datasets. We delineate bulk-tissue gene expression into single cell-type gene expression and integrate clinical and pathologic traits, single nucleotide variation, and deconvoluted gene expression for the construction of cell type-specific predictive network models. Here, we focus on neuron-specific network models and prioritize 19 predicted key drivers modulating Alzheimer's pathology, which we then validate by knockdown in human induced pluripotent stem cell-derived neurons. We find that neuronal knockdown of 10 of the 19 targets significantly modulates levels of amyloid-beta and/or phosphorylated tau peptides, most notably JMJD6. We also confirm our network structure by RNA sequencing in the neurons following knockdown of each of the 10 targets, which additionally predicts that they are upstream regulators of REST and VGF. Our work thus identifies robust neuronal key drivers of the Alzheimer's-associated network state which may represent therapeutic targets with relevance to both amyloid and tau pathology in Alzheimer's disease. A network analysis on deconvoluted bulk transcriptomic data from human Alzheimer's disease cohorts identifies several potential key disease drivers, including JMJD6. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) regulate fundamental biological processes by silencing mRNA targets and are dysregulated in many diseases. Therefore, miRNA replacement or inhibition can be harnessed as potential therapeutics. However, existing strategies for miRNA modulation using oligonucleotides and gene therapies are challenging, especially for neurological diseases, and none have yet gained clinical approval. We explore a different approach by screening a biodiverse library of small molecule compounds for their ability to modulate hundreds of miRNAs in human induced pluripotent stem cell-derived neurons. We demonstrate the utility of the screen by identifying cardiac glycosides as potent inducers of miR-132, a key neuroprotective miRNA downregulated in Alzheimer's disease and other tauopathies. Coordinately, cardiac glycosides downregulate known miR-132 targets, including Tau, and protect rodent and human neurons against various toxic insults. More generally, our dataset of 1370 drug-like compounds and their effects on the miRNome provides a valuable resource for further miRNA-based drug discovery. Regulatory miRNAs have significant therapeutic potential. Here the authors developed a screen to identify small molecule drugs that modulate miRNome profiles in human neurons and validated cardiac glycosides as inducers of the neuroprotective miR-132. [ABSTRACT FROM AUTHOR]

Understanding processes leading to disease emergence is important for effective disease management and prevention of future epidemics. Utilizing whole genome sequencing, we studied the phylogenetic relationship and diversity of two populations of the bacterial oak pathogen Lonsdalea quercina from western North America (Colorado and California) and compared these populations to other Lonsdalea species found worldwide. Phylogenetic analysis separated Colorado and California populations into two Lonsdalea clades, with genetic divergence near species boundaries, suggesting long isolation and populations that differ in genetic structure and distribution and possibly their polyphyletic origin. Genotypes collected from different host species and habitats were randomly distributed within the California cluster. Most Colorado isolates from introduced planted trees, however, were distinct from three isolates collected from a natural stand of Colorado native Quercus gambelii, indicating cryptic population structure. The California identical core genotypes distribution varied, while Colorado identical core genotypes were always collected from neighboring trees. Despite its recent emergence, the Colorado population had higher nucleotide diversity, possibly due to its long presence in Colorado or due to migrants moving with nursery stock. Overall, results suggest independent pathogen emergence in two states likely driven by changes in host-microbe interactions due to ecosystems changes. Further studies are warranted to understand evolutionary relationships among L. quercina from different areas, including the red oak native habitat in northeastern USA. [ABSTRACT FROM AUTHOR]

Background: Demographic changes worldwide are leading to pressures on health services, with hospital admissions representing an important contributor. Here, we report admission types experienced by older people and examine baseline risk factors for subsequent admission/death, from the community-based Hertfordshire Cohort Study. Methods: 2997 participants (1418 women) completed a baseline questionnaire and clinic visit to characterize their health. Participants were followed up from baseline (1998–2004, aged 59–73 years) until December 2018 using UK Hospital Episode Statistics and mortality data, which report clinical outcomes using ICD-10 coding. Baseline characteristics in relation to the risk of admission/death during follow-up were examined using sex-stratified univariate logistic regression. Results: During follow-up, 36% of men and 26% of women died and 93% of men and 92% of women had at least one hospital admission; 6% of men and 7% of women had no admissions and were alive at end of follow-up. The most common types of admission during follow-up were cardiovascular (ever experienced: men 71%, women 68%) and respiratory (men 40%, women 34%). In both sexes, baseline risk factors that were associated (p < 0.05) with admission/death during follow-up were older age, poorer SF-36 physical function, and poorer self-rated health. In men, manual social class and a history of smoking, and in women, higher BMI, not owning one's home, and a minor trauma fracture since age 45, were also risk factors for admission/death. Conclusions: Sociodemographic factors were related to increased risk of admission/death but a small proportion experienced no admissions during this period, suggesting that healthy ageing is achievable. [ABSTRACT FROM AUTHOR]

Predicting where invasive plants are likely to spread and become abundant is critical for informing invasive plant management. Species distribution models are a key tool for informing the geography of invasion risk, but most distribution models are limited by their use of presence data, including no information on invader population abundance. In this study, we ask how habitat suitability varies for different levels of abundance for three invasive plants: stiltgrass (Microstegium vimineum), sericea lespedeza (Lespedeza cuneata), and privet (Ligustrum sinense). For each species, we used an ensemble distribution modeling approach to compare suitability for invasion estimated from subsets of point location data: all presences vs. locations with percent cover ≥ 1%, ≥ 5%, ≥ 10%, ≥ 25%, and ≥ 50%. For all species, the total area predicted as suitable for abundant populations was 32%–68% less than the area predicted as suitable for presence. For stiltgrass and sericea lespedeza, the area suitable for invasion decreased when predicted from higher levels of abundance, whereas for privet, suitable area was similar across abundance levels. Stiltgrass and sericea lespedeza are therefore likely to become highly abundant in a smaller portion of their ranges, while privet could become highly abundant anywhere it can establish at low abundance. Different environmental predictors explained suitability for presence versus abundance, suggesting the environmental niche associated with presence differs from that associated with high population abundance. Analyses of more species and growth forms are still needed, but our results combined with previous studies consistently show that fitting distribution models to point locations with ≥ 5–10% cover refines range maps and can produce a more targeted assessment of invasion risk. [ABSTRACT FROM AUTHOR]

Azaspiracids (AZAs) are a group of polyether marine algal toxins known to accumulate in shellfish, posing a risk to human health and the seafood industry. Analysis of AZAs is typically performed using LC–MS, which can suffer from matrix effects that significantly impact the accuracy of measurement results. While the use of isotopic internal standards is an effective approach to correct for these effects, isotopically labelled standards for AZAs are not currently available. In this study, 18O-labelled AZA1, AZA2, and AZA3 were prepared by reaction with H218O under acidic conditions, and the reaction kinetics and sites of incorporation were studied using LC–HRMS/MS aided by mathematical analysis of their isotope patterns. Analysis of the isotopic incorporation in AZA1 and AZA3 indicated the presence of four exchangeable oxygen atoms. Excessive isomerization occurred during preparation of 18O-labelled AZA2, suggesting a role for the 8-methyl group in the thermodynamic stability of AZAs. Neutralized mixtures of 18O-labelled AZA1 and AZA3 were found to maintain their isotopic and isomeric integrities when stored at −20 °C and were used to develop an isotope-dilution LC–MS method which was applied to reference materials of shellfish matrices containing AZAs, demonstrating high accuracy and excellent reproducibility. Preparation of isotopically labelled compounds using the isotopic exchange method, combined with the kinetic analysis, offers a feasible way to obtain isotopically labelled internal standards for a wide variety of biomolecules to support reliable quantitation. [ABSTRACT FROM AUTHOR]

Shark populations globally are facing catastrophic declines. Ecotourism has been posited as a potential solution to many of the issues facing shark conservation, yet increasingly studies suggest that such activity may negatively influence aspects of shark ecology and so further pressure declining populations. Here we combine UAV videography with deep learning algorithms, multivariate statistics and hidden Markov models (HMM) to quantitatively investigate the behavioural consequences of ecotourism in the whale shark (Rhincodon typus). We find that ecotourism increases the probability of sharks being in a disturbed behavioural state, likely increasing energetic expenditure and potentially leading to downstream ecological effects. These results are only recovered when fitting models that account for individual variation in behavioural responses and past behavioural history. Our results demonstrate that behavioural responses to ecotourism are context dependent, as the initial behavioural state is important in determining responses to human activity. We argue that models incorporating individuality and context-dependence should, wherever possible, be incorporated into future studies investigating the ecological impacts of shark ecotourism, which are only likely to increase in importance given the expansion of the industry and the dire conservation status of many shark species. [ABSTRACT FROM AUTHOR]

Purpose: To review the rising prevalence of osteopenia and osteoporosis in sub-Saharan Africa and the challenges this poses to governments and healthcare services. Using existing studies, we compare the prevalence of osteopenia and osteoporosis in men and women from sub-Saharan Africa to US and UK cohorts. Context-specific disparities in healthcare are discussed particularly the challenges in diagnosis and treatment of osteoporosis. Recent Findings: There are few epidemiological data describing the burden of osteoporosis in sub-Saharan Africa. In the studies and cohorts presented here, osteoporosis prevalence varies by sex, country and area of residence, but is generally higher in African populations, than has previously been appreciated. Risk factors contributing to poorer bone health include HIV, malnutrition and "inflammaging." Summary: Reprioritization towards care of ageing populations is urgently required. Equitable access to implementable preventative strategies, diagnostic services, treatments and pathways of care for bone health (for example embedded within HIV services) need now to be recognized and addressed by policy makers. [ABSTRACT FROM AUTHOR]

Objectives: Treatment and outcomes of acute stroke have been revolutionised by mechanical thrombectomy. Deep learning has shown great promise in diagnostics but applications in video and interventional radiology lag behind. We aimed to develop a model that takes as input digital subtraction angiography (DSA) videos and classifies the video according to (1) the presence of large vessel occlusion (LVO), (2) the location of the occlusion, and (3) the efficacy of reperfusion. Methods: All patients who underwent DSA for anterior circulation acute ischaemic stroke between 2012 and 2019 were included. Consecutive normal studies were included to balance classes. An external validation (EV) dataset was collected from another institution. The trained model was also used on DSA videos post mechanical thrombectomy to assess thrombectomy efficacy. Results: In total, 1024 videos comprising 287 patients were included (44 for EV). Occlusion identification was achieved with 100% sensitivity and 91.67% specificity (EV 91.30% and 81.82%). Accuracy of location classification was 71% for ICA, 84% for M1, and 78% for M2 occlusions (EV 73, 25, and 50%). For post-thrombectomy DSA (n = 194), the model identified successful reperfusion with 100%, 88%, and 35% for ICA, M1, and M2 occlusion (EV 89, 88, and 60%). The model could also perform classification of post-intervention videos as mTICI < 3 with an AUC of 0.71. Conclusions: Our model can successfully identify normal DSA studies from those with LVO and classify thrombectomy outcome and solve a clinical radiology problem with two temporal elements (dynamic video and pre and post intervention). Key Points: • DEEP MOVEMENT represents a novel application of a model applied to acute stroke imaging to handle two types of temporal complexity, dynamic video and pre and post intervention. • The model takes as an input digital subtraction angiograms of the anterior cerebral circulation and classifies according to (1) the presence or absence of large vessel occlusion, (2) the location of the occlusion, and (3) the efficacy of thrombectomy. • Potential clinical utility lies in providing decision support via rapid interpretation (pre thrombectomy) and automated objective gradation of thrombectomy outcomes (post thrombectomy). [ABSTRACT FROM AUTHOR]

There has been limited characterisation of bat-borne coronaviruses in Europe. Here, we screened for coronaviruses in 48 faecal samples from 16 of the 17 bat species breeding in the UK, collected through a bat rehabilitation and conservationist network. We recovered nine complete genomes, including two novel coronavirus species, across six bat species: four alphacoronaviruses, a MERS-related betacoronavirus, and four closely related sarbecoviruses. We demonstrate that at least one of these sarbecoviruses can bind and use the human ACE2 receptor for infecting human cells, albeit suboptimally. Additionally, the spike proteins of these sarbecoviruses possess an R-A-K-Q motif, which lies only one nucleotide mutation away from a furin cleavage site (FCS) that enhances infectivity in other coronaviruses, including SARS-CoV-2. However, mutating this motif to an FCS does not enable spike cleavage. Overall, while UK sarbecoviruses would require further molecular adaptations to infect humans, their zoonotic risk warrants closer surveillance. Certain bats species have previously been identified as ancestral sources of coronaviruses that infect humans but there is limited data on the genomic diversity or zoonotic potential of viruses infecting bats in the UK. Here, the authors use deep sequencing and in vitro assays to characterise coronaviruses recovered from 48 bat faecal samples. [ABSTRACT FROM AUTHOR]

Between-scanner differences in measures of bone and body composition can obscure or exaggerate physiological differences in multi-site studies or the magnitude of changes in longitudinal studies. We conducted a cross-calibration study at two bone imaging centres in The Gambia, West Africa where DXA (dual-energy X-ray absorptiometry) and pQCT (peripheral Quantitative-Computed Tomography) are routinely used. Repeat scans were obtained from 64 Gambian adults (58% Male) aged Mean(SD) 30.9 (13.5) years with Mean(SD) body mass index (BMI) 21.7 (4.0) kg/m2, using DXA (GE Lunar iDXA, whole body [WB], total hip [TH], lumbar spine [LS]) and pQCT (Stratec XCT2000L/XCT2000, tibia 4%, 50% sites). Between-scanner differences were tested using paired t tests (p < 0.05). Between-scanner correlation was explored with linear regression, and cross-calibration equations derived. Bland–Altman analysis investigated machine trend/bias. When differences were detected (p < 0.05), cross-calibration equations were applied to urban values, with t tests and Bland Altman analysis repeated. Between-scanner differences exceeded the predefined level of statistical significance (p < 0.05) for WB aBMD and BA; all pQCT measures vBMD, BMC, cortical cross-sectional area (CSA) and stress–strain index (SSI). Between-scanner correlation was high (R2:0.92–0.99), except pQCT Mu.Den (R2 = 0.51). Bland Altman plots indicated bias increased with increasing BMD. Cross-calibration equations attenuated all between-scanner differences and systematic bias. Cross-calibration, particularly of pQCT scanners, is an important consideration in multi-site studies particularly where between population comparisons are intended. Our experiences and findings may be generalisable to other resource-limited settings where the logistics of sourcing parts and in-country repair may result in lengthy scanner downtime. [ABSTRACT FROM AUTHOR]

The primary objective of this study was to examine the effects of a bespoke and innovative six-week online Mindfulness-based Social Work and Self-Care (MBSWSC) programme on the stress, feelings of burnout, anxiety, depression, and well-being of a sample of social workers. This secondary objective was to examine the effectiveness of MBSWSC at improving a number of potentially important mindfulness-based programme mechanisms of action, including mindfulness, attention regulation (decentering), acceptance, self-compassion, non-attachment, aversion, worry and rumination. A randomised controlled trial with repeated measures (pre-post intervention) was conducted to evaluate the effects of MBSWSC against an active control. The active control was a modified mindfulness-based programme which focussed on supporting increases in mindfulness and self-compassion in social workers with a view to improving the same primary study outcomes. Sixty-two participants were randomly allocated to MBSWSC (n = 33) or the active control (n = 29). When compared to the active control group, the MBSWSC programme was found to be significantly superior at improving stress, emotional exhaustion, anxiety, and depression. MBSWSC was also superior to the active control at improving acceptance, mindfulness, non-attachment, attention regulation (decentering) and worry of the social workers in this study. The results suggest that MBSWSC is a very useful therapeutic programme, which has the capacity to improve a range of important mental health and well-being outcomes for social workers. The results also indicate that the MBSWSC programme has the capacity to improve a range of important mindfulness-based mechanisms of action. Trial registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05519267 (retrospectively registered). [ABSTRACT FROM AUTHOR]

Purpose: Neovascular age-related macular degeneration (nAMD) is a major global cause of blindness. Whilst anti-vascular endothelial growth factor (anti-VEGF) treatment is effective, response varies considerably between individuals. Thus, patients face substantial uncertainty regarding their future ability to perform daily tasks. In this study, we evaluate the performance of an automated machine learning (AutoML) model which predicts visual acuity (VA) outcomes in patients receiving treatment for nAMD, in comparison to a manually coded model built using the same dataset. Furthermore, we evaluate model performance across ethnic groups and analyse how the models reach their predictions. Methods: Binary classification models were trained to predict whether patients' VA would be 'Above' or 'Below' a score of 70 one year after initiating treatment, measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The AutoML model was built using the Google Cloud Platform, whilst the bespoke model was trained using an XGBoost framework. Models were compared and analysed using the What-if Tool (WIT), a novel model-agnostic interpretability tool. Results: Our study included 1631 eyes from patients attending Moorfields Eye Hospital. The AutoML model (area under the curve [AUC], 0.849) achieved a highly similar performance to the XGBoost model (AUC, 0.847). Using the WIT, we found that the models over-predicted negative outcomes in Asian patients and performed worse in those with an ethnic category of Other. Baseline VA, age and ethnicity were the most important determinants of model predictions. Partial dependence plot analysis revealed a sigmoidal relationship between baseline VA and the probability of an outcome of 'Above'. Conclusion: We have described and validated an AutoML-WIT pipeline which enables clinicians with minimal coding skills to match the performance of a state-of-the-art algorithm and obtain explainable predictions. [ABSTRACT FROM AUTHOR]

Purpose: Intrathecal gadolinium magnetic resonance (MR) myelography can be used to localize various types of spinal cerebrospinal fluid (CSF) leaks; however, its diagnostic yield is not well known. We sought to determine the diagnostic yield of MR myelography in patients with spontaneous intracranial hypotension. Methods: A retrospective review was performed on all patients who had undergone intrathecal gadolinium MR myelography at our institution from 2002 to 2020 for suspected spinal CSF leak. The MR myelography images were reviewed for the presence or absence of a spinal CSF leak site. Images were also evaluated for the presence an extradural fluid collection. Results: A total of 97 patients were included in the final cohort. The average age was 52.6 years; 67.0% were female, 4 patients underwent 2 examinations each, yielding a total of 101 MR myelograms. The source of a spinal CSF leak was localized in 14 patients. The diagnostic yield for CSF leak localization on intrathecal gadolinium MR myelography was 14/101 (13.9%) per GdM examination and 14/97 (14.4%) per patient. Among the subset of patients without extradural fluid collections, the yield was 15.7% per examination. All detected leaks were either CSF-venous fistulas or distal nerve root sleeve tears. Conclusion: Intrathecal gadolinium MR myelography is capable of localizing CSF-venous fistulas and distal nerve root sleeve tears; however, our data show that it has a limited diagnostic yield. We suggest that other modalities may be a better first step before attempting intrathecal gadolinium MR myelography. [ABSTRACT FROM AUTHOR]

It is unclear if changes in public behaviours, developments in COVID-19 treatments, improved patient care, and directed policy initiatives have altered outcomes for minority ethnic groups in the second pandemic wave. This was a prospective analysis of patients aged ≥ 16 years having an emergency admission with SARS-CoV-2 infection between 01/09/2020 and 17/02/2021 to acute NHS hospitals in east London. Multivariable survival analysis was used to assess associations between ethnicity and mortality accounting for predefined risk factors. Age-standardised rates of hospital admission relative to the local population were compared between ethnic groups. Of 5533 patients, the ethnic distribution was White (n = 1805, 32.6%), Asian/Asian British (n = 1983, 35.8%), Black/Black British (n = 634, 11.4%), Mixed/Other (n = 433, 7.8%), and unknown (n = 678, 12.2%). Excluding 678 patients with missing data, 4855 were included in multivariable analysis. Relative to the White population, Asian and Black populations experienced 4.1 times (3.77–4.39) and 2.1 times (1.88–2.33) higher rates of age-standardised hospital admission. After adjustment for various patient risk factors including age, sex, and socioeconomic deprivation, Asian patients were at significantly higher risk of death within 30 days (HR 1.47 [1.24–1.73]). No association with increased risk of death in hospitalised patients was observed for Black or Mixed/Other ethnicity. Asian and Black ethnic groups continue to experience poor outcomes following COVID-19. Despite higher-than-expected rates of hospital admission, Black and Asian patients also experienced similar or greater risk of death in hospital since the start of the pandemic, implying a higher overall risk of COVID-19 associated death in these communities. [ABSTRACT FROM AUTHOR]

Alphaviruses, like many other arthropod-borne viruses, infect vertebrate species and insect vectors separated by hundreds of millions of years of evolutionary history. Entry into evolutionarily divergent host cells can be accomplished by recognition of different cellular receptors in different species, or by binding to receptors that are highly conserved across species. Although multiple alphavirus receptors have been described1–3, most are not shared among vertebrate and invertebrate hosts. Here we identify the very low-density lipoprotein receptor (VLDLR) as a receptor for the prototypic alphavirus Semliki forest virus. We show that the E2 and E1 glycoproteins (E2–E1) of Semliki forest virus, eastern equine encephalitis virus and Sindbis virus interact with the ligand-binding domains (LBDs) of VLDLR and apolipoprotein E receptor 2 (ApoER2), two closely related receptors. Ectopic expression of either protein facilitates cellular attachment, and internalization of virus-like particles, a VLDLR LBD–Fc fusion protein or a ligand-binding antagonist block Semliki forest virus E2–E1-mediated infection of human and mouse neurons in culture. The administration of a VLDLR LBD–Fc fusion protein has protective activity against rapidly fatal Semliki forest virus infection in mouse neonates. We further show that invertebrate receptor orthologues from mosquitoes and worms can serve as functional alphavirus receptors. We propose that the ability of some alphaviruses to infect a wide range of hosts is a result of their engagement of evolutionarily conserved lipoprotein receptors and contributes to their pathogenesis.Studies using viral coat glycoproteins show that alphaviruses can enter cells via the very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2), members of an evolutionarily conserved family of lipoprotein receptors. [ABSTRACT FROM AUTHOR]

Nitrogen stable isotopes (δ15N) are used to study food web and foraging dynamics due to the step-wise enrichment of tissues with increasing trophic level, but they rely on the isoscape baseline that varies markedly in the Arctic due to the interplay between Atlantic- and Pacific-origin waters. Using a hierarchy of simulations with a state-of-the-art ocean-biogeochemical model, we demonstrate that the canonical isotopic gradient of 2–3‰ between the Pacific and Atlantic sectors of the Arctic Ocean has grown to 3–4‰ and will continue to expand under a high emissions climate change scenario by the end of the twenty-first century. δ15N increases in the Pacific-influenced high Arctic due to increased primary production, while Atlantic sector decreases result from the integrated effects of Atlantic inflow and anthropogenic inputs. While these trends will complicate longitudinal food web studies using δ15N, they may aid those focussed on movement as the Arctic isoscape becomes more regionally distinct. [ABSTRACT FROM AUTHOR]

Introduction: To assess inter-device agreement in optical coherence tomography-derived retinal thickness measurements in patients with known macular conditions between spectral-domain and swept-source optical coherence tomography (OCT). Methods: Two hundred seventy-two subjects were included in the study. They consisted of 91 male (33.5%) and 181 female (66.5%) subjects, and 132 left (48.5%) and 140 right (51.5%) eyes. Each subject underwent spectral-domain OCT (SD-OCT, Spectralis, Heidelberg Engineering; RTVue XR Avanti XR HD, Optovue) and swept-source OCT (SS-OCT; DRI-OCT-1, Atlantis, Topcon) in a single imaging session performed by the same clinical trial-certified technician. The comparison of retinal thickness reproducibility between devices was performed using Bland–Altman analyses and across the entire data set using the intraclass correlation coefficient (ICC). Results: The ICC of the retinal thickness measurements (95% confidence interval) made using all three OCT instruments was 0.81 (0.77–0.84). The mean difference in mean retinal thickness between Spectralis SD-OCT and Topcon SS-OCT was 59.1 μm (95% limit of agreement [LoA] −21.7 to 139.8 μm). The mean difference in mean retinal thickness between Optovue SD-OCT and Topcon SS-OCT was 21.8 μm (95% LoA −34.7 to 78.3 μm). Conclusions: Retinal layer thickness measurements vary between SS-OCT and SD-OCT devices. We describe inter-device agreement in retinal thickness between SS-OCT and SD-OCT in patients with macular conditions. Clinicians should be aware of the differences in retinal thickness values when imaging patients using different OCT devices and should consider using the same OCT device model in order to monitor clinical change. Trial Registration: ClinicalTrials.gov Identifier (NCT02828215). [ABSTRACT FROM AUTHOR]

The Competition on Spatial Statistics for Large Datasets ran in late 2020 and early 2021 and attracted several researchers in spatial statistics, including some in our group at the University of Wollongong, Australia. In this discussion paper, we first summarize our submission to the competition. We then discuss some aspects of the competition and give suggestions for future competitions with regard to the datasets and the assessment methods used. [ABSTRACT FROM AUTHOR]

The complement system is a potent mediator of ischemia–reperfusion injury (IRI), which detrimentally affects the function and survival of transplanted kidneys. Human complement receptor 1 (HuCR1) is an integral membrane protein that inhibits complement activation by blocking the convertases that activate C3 and C5. We have previously reported that CSL040, a truncated form of recombinant soluble HuCR1 (sHuCR1), has enhanced complement inhibitory activity and improved pharmacokinetic properties compared to the parent molecule. Here, we compared the capacity of CSL040 and full-length sHuCR1 to suppress complement-mediated organ damage in a mouse model of warm renal IRI. Mice were treated with two doses of CSL040 or sHuCR1, given 1 h prior to 22 min unilateral renal ischemia and again 3 h later. 24 h after reperfusion, mice treated with CSL040 were protected against warm renal IRI in a dose-dependent manner, with the highest dose of 60 mg/kg significantly reducing renal dysfunction, tubular injury, complement activation, endothelial damage, and leukocyte infiltration. In contrast, treatment with sHuCR1 at a molar equivalent dose to 60 mg/kg CSL040 did not confer significant protection. Our results identify CSL040 as a promising therapeutic candidate to attenuate renal IRI and demonstrate its superior efficacy over full-length sHuCR1 in vivo. [ABSTRACT FROM AUTHOR]