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UK Biobank—a unique resource for discovery and translation research on genetics and neurologic disease
Get PDFUK Biobank is a large-scale prospective study with extensive genetic and phenotypic data from half a million adults. Participants, aged 40 to 69, were recruited from the general UK population between 2006 and 2010. During recruitment, participants completed questionnaires covering lifestyle and medical history, underwent physical measurements, and provided biological samples for long-term storage. Whole-cohort assays have been conducted, including biochemical markers, genotyping, whole-exome and whole-genome sequencing, as well as proteomics and metabolomics in large subsets of the cohort, with potential for additional assays in the future. Participants consented to link their data to electronic health records, enabling the identification of health outcomes over time. Research studies using UK Biobank data have already enhanced our understanding of the role of genetic variation in neurologic disease, offering insights into potential therapeutic approaches. The integration of genetic and imaging data has led to significant discoveries regarding the relationship between genetic variants and brain structure and function, particularly in Alzheimer disease and Parkinson disease. Genetic data have also allowed Mendelian randomization analyses to be performed, enabling further investigation into the causality of associations between behavioral and physiologic factors-such as diet and blood pressure-and neurologic outcomes. Furthermore, genetic and proteomic data have been particularly useful in identifying new drug targets for neurologic disease and in enhancing risk prediction algorithms that are increasingly applied in clinical practice to identify those at higher risk. As UK Biobank continues to be enhanced, and the cases of neurologic disease accrue over time, the study will become increasingly valuable for both discovery and translational research on genetics and neurologic disease
Lucy L′Ralph In-flight Calibration and Results at (152830) Dinkinesh
Get PDFThe L’Ralph instrument is a key component of NASA’s Lucy mission, intended to provide spectral image data of multiple Jupiter Trojans. The instrument operates from ∼0.35 to 4 μm using two focal plane assemblies: a 350–950 nm multispectral imager, Multi-spectral Visible Imaging Camera (MVIC), and a 0.97–4 μm imaging spectrometer, Linear Etalon Imaging Spectral Array (LEISA). Instrument calibration was established through ground testing before launch and has been monitored during cruise utilizing internal calibration sources and stellar targets. In-flight data have shown that the instrument thermal performance is exceeding expectations, allowing for early updates to LEISA radiometric and pointing calibrations. MVIC radiometric performance remains stable more than 3 yr since launch. The serendipitous identification of a new flyby target, (152830) Dinkinesh, allowed testing of instrument performance and interleaved LEISA and MVIC acquisitions on an asteroid target. Both MVIC and LEISA obtained data of Dinkinesh and its moon, Selam, demonstrating that they show good spectral agreement with an S- or Sq-type asteroid, along with evidence of a 3 μm absorption feature
A National Epidemiologic Mixed-methods Study on Depression, Anxiety, Substance Use, Treatment Needs and Barriers and Facilitators to Treatment Among Medical Students
Get PDFBackgroundResearch on the mental health of medical students enrolled in Paraguayan universities has mainly examined the prevalence of anxiety and depression, with limited exploration of treatment access, barriers, and facilitators. Additionally, substance use, such as alcohol and other substances, is of significant concern because of its association with mental health issues. This study aimed to assess the prevalence of depression, anxiety, and substance use disorders, as well as to identify barriers and facilitators influencing medical students' access to mental health and substance use treatment in the Republic of Paraguay.MethodsA national mixed-methods cross-sectional study was conducted with 532 medical students from public and private universities across the Republic of Paraguay. Data were collected via an online survey in 2024 using validated tools to measure mental health conditions, including alcohol and other substance use. Qualitative responses regarding barriers to and facilitators of treatment were categorized and analyzed.ResultsThe findings revealed high rates of anxiety (76.8%) and depression (39.3%). Substance use was also concerning, with 11.1% reporting alcohol-related problems and 1.9% reporting other substance-related problems. Barriers to seeking treatment included confidentiality concerns, stigma, and financial constraints, while facilitators included trust in the mental health system, emotional distress, and accessibility. Despite the availability of these services, many students felt unsupported by their universities.ConclusionsParaguayan universities must urgently address the stigma surrounding mental health and substance use, improve service accessibility, and build trust in the academic environment. Tackling these issues is crucial for safeguarding medical students' mental health and future
Addressing grand ecological challenges in aquatic ecosystems: how can mesocosms be used to advance solutions?
Get PDFRapid and drastic anthropogenic impacts are affecting global biogeochemical processes and driving biodiversity loss across Earth's ecosystems. In aquatic ecosystems, species distributions are shifting, abundances of many species have declined dramatically, and many are threatened with extinction. In addition to loss of diversity, the ecosystem functions, processes and services on which humans depend are also being heavily impacted. Addressing these challenges not only requires direct action to mitigate environmental impacts but also innovative approaches to identify, quantify and treat their effects in the environment. Mesocosms are valuable tools for achieving these goals as they provide controlled environments for evaluating effects of stressors and testing novel mitigation measures at multiple levels of biological organisation. Here, we summarise discussions from a survey of marine and freshwater researchers who use mesocosm systems to synthesise their opportunities and limitations for advancing solutions to grand ecological challenges in aquatic ecosystems. While most research utilising mesocosm systems in aquatic ecology has focused on quantifying the effects of environmental threats, there is a largely unexplored potential for using them to test solutions. To overcome spatio‐temporal constraints, there are opportunities to scale up the size and time‐scales of mesocosm studies, or alternatively, test the outcomes of habitat‐scale restoration at a smaller scale. Enhancing connectivity in future studies can help to overcome the limitation of isolation and test an important aspect of ecological recovery. Conducting ‘metacosm' studies: coordinated, distributed mesocosm experiments spanning wide climatic and environmental gradients and utilising more regression‐based experimental designs can help to tackle the challenge of context dependent results. Finally, collaboration of theoretical, experimental and applied ecologists and biogeochemists with environmental engineers and technological developers will be necessary to develop and test the tools required to advance solutions to the impacts of human activities on Earth's vulnerable aquatic ecosystems
Bridging the human–AI knowledge gap through concept discovery and transfer in AlphaZero
Get PDFAI systems have attained superhuman performance across various domains. If the hidden knowledge encoded in these highly capable systems can be leveraged, human knowledge and performance can be advanced. Yet, this internal knowledge is difficult to extract. Due to the vast space of possible internal representations, searching for meaningful new conceptual knowledge can be like finding a needle in a haystack. Here, we introduce a method that extracts new chess concepts from AlphaZero, an AI system that mastered chess via self-play without human supervision. Our method excavates vectors that represent concepts from AlphaZero’s internal representations using convex optimization, and filters the concepts based on teachability (whether the concept is transferable to another AI agent) and novelty (whether the concept contains information not present in human chess games). These steps ensure that the discovered concepts are useful and meaningful. For the resulting set of concepts, prototypes (chess puzzle–solution pairs) are presented to experts for final validation. In a preliminary human study, four top chess grandmasters (all former or current world chess champions) were evaluated on their ability to solve concept prototype positions. All grandmasters showed improvement after the learning phase, suggesting that the concepts are at the frontier of human understanding. Despite the small scale, our result is a proof of concept demonstrating the possibility of leveraging knowledge from a highly capable AI system to advance the frontier of human knowledge; a development that could bear profound implications and shape how we interact with AI systems across many applications
Investigating the accuracy of tropical woody stem CO 2 efflux estimates: scaling methods, and vertical and diel variation
Get PDFSummary: Stem CO2 efflux (EA) significantly contributes to autotrophic and ecosystem respiration in tropical forests, but field methodologies often introduce biases and uncertainty. This study evaluates these biases and their impact on scaling EA at the stand‐level. Diel and vertical patterns of EA were investigated, along with the accuracy of estimating stem surface area from allometric equations vs terrestrial light dection and ranging (LiDAR) scanning (TLS) in Maliau Basin Conservation Area, Sabah, Malaysian Borneo. Diel EA exhibited no uniform pattern due to inter‐tree variability, but results suggest measuring EA before 15:00 h. EA was significantly higher on buttresses and above the first major branching point, but vertical variations in EA did not impact stand‐level EA when stem surface area was accurately estimated. Allometric equations underestimated total stem surface area by c. 40% compared with TLS, but applying a site‐specific correction factor yielded a similar stand‐level EA and total stem surface area to TLS. This study provides guidance for measuring EA in the field and suggests that measuring at one time point and one height along the stem can produce accurate results if conducted using the correct time frame and if stem surface area is accurately estimated
Effects of transfusing older red blood cells on patient outcomes in critical illness: A retrospective cohort study
Get PDFBackground and Objectives: Randomized controlled trials have demonstrated morbidity and mortality in critically ill patients are unaffected by transfusing fresh (<7 days old) packed red blood cells (pRBCs); however, there is limited evidence regarding transfusion with pRBCs nearing expiry (35–42 days). The aim of this study was to investigate the effects of transfusing pRBCs close to the end of shelf life (≥35 days) on clinical outcomes in critically ill patients. Materials and Methods: A retrospective observational analysis of data obtained from centralized electronic medical records (2007–2013), sourced from all public and licensed private hospitals in Queensland, Australia, with intensive care units. Multivariate logistic and linear regressions were used to analyse association between transfusion with pRBCs nearing expiry, and in‐hospital mortality, hospital length of stay (HLOS) and rate of discharge home. Comparisons are presented as odds ratios (ORs) with 95% confidence intervals (CIs). Results: The study included 10,350 critically ill adult patients transfused ≥1 unit of non‐irradiated pRBCs (64,594 pRBCs units transfused). Receiving at least 1‐unit pRBCs ≥ 35 days old was associated with increased mortality (OR 1.21 [95% CI 1.06–1.38]; p = 0.005), decreased discharge to usual residence (OR 0.81 [95% CI 0.73–0.89]; p < 0.0001) and increased hospital LOS (estimate 2.55 [95% CI 1.60–3.49]; p < 0.0001). There was also association with increased sepsis (OR 1.27 [95% CI 1.13–1.42]; p < 0.0001) and delirium (OR 1.25 [95% CI 1.06–1.49]; p = 0.01). Conclusion: Transfusion of ≥1‐unit pRBCs ≥ 35 days old was associated with higher morbidity and mortality in critically ill patients
Considerations and recommendations from the ISMRM diffusion study group for preclinical diffusion MRI: part 1: in vivo small-animal imaging
Get PDFSmall-animal diffusion MRI (dMRI) has been used for methodological development and validation, characterizing the biological basis of diffusion phenomena, and comparative anatomy. The steps from animal setup and monitoring, to acquisition, analysis, and interpretation are complex, with many decisions that may ultimately affect what questions can be answered using the resultant data. This work aims to present selected considerations and recommendations from the diffusion community on best practices for preclinical dMRI of in vivo animals. We describe the general considerations and foundational knowledge that must be considered when designing experiments. We briefly describe differences in animal species and disease models and discuss why some may be more or less appropriate for different studies. We, then, give recommendations for in vivo acquisition protocols, including decisions on hardware, animal preparation, and imaging sequences, followed by advice for data processing including preprocessing, model-fitting, and tractography. Finally, we provide an online resource that lists publicly available preclinical dMRI datasets and software packages to promote responsible and reproducible research. In each section, we attempt to provide guides and recommendations, but also highlight areas for which no guidelines exist (and why), and where future work should focus. Although we mainly cover the central nervous system (on which most preclinical dMRI studies are focused), we also provide, where possible and applicable, recommendations for other organs of interest. An overarching goal is to enhance the rigor and reproducibility of small animal dMRI acquisitions and analyses, and thereby advance biomedical knowledge
The Brief International Cognitive Assessment in Multiple Sclerosis ( BICAMS ): Regression‐based norms for German‐speaking countries
Get PDFBackground and purpose: Cognitive impairment in multiple sclerosis (MS) is common and is associated with problems in employment, driving ability, and quality of life. Since cognitive impairment at time of diagnosis is predictive of disability progression, early assessment and annual monitoring is recommended. The Brief International Cognitive Assessment in Multiple Sclerosis (BICAMS) was introduced as a time‐efficient screening tool that can easily be applied in standard clinical care. However, besides application, tests need to be analysed and the raw values obtained must be interpreted accordingly. Since normative values have not been available for German‐speaking countries, BICAMS has not been implemented in clinical routine. The aim of this study was to calculate German normative BICAMS data to improve the current diagnostic process for people with MS. Methods: Healthy control subjects in different age categories were recruited to enable regression‐based norm analysis. Raw scores for each BICAMS test were converted into scaled scores before they were regressed for age, age squared, gender, and education. The obtained scores were then normalised to a z‐score by dividing the difference between the scaled score and the predicted score by the root mean squared error of the model. Results: In all, 237 HCs were recruited (68.8% female, 31.2% male) and examined with BICAMS. Datasets entered the regression‐based norms analysis and formed the basis for a final z‐score calculation. To simplify handling in everyday clinical practice, nomograms and look‐up tables were created which provide clinicians with age‐ and education‐corrected norms. Conclusion: Our work fills the gaps between BICAMS application, evaluation and interpretation and will make a significant contribution to more regular cognitive assessment of MS patients