791 research outputs found

    Dietary Iron, Anemia Markers, Cognition, and Quality of Life in Older Community-Dwelling Subjects at High Cardiovascular Risk

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    Anemia causes hypo-oxygenation in the brain, which could lead to cognitive disorders. We examined dietary iron intake as well as anemia markers (i.e., hemoglobin, hematocrit, mean corpuscular volume) and diabetes coexistence in relation to neuropsychological function and quality of life. In this study, 6117 community-dwelling adults aged 55-75 years (men) and 60-75 years (women) with overweight/obesity and metabolic syndrome were involved. We performed the Mini-Mental State Examination (MMSE), the Trail Making Test parts A and B (TMT-A/B), Semantic Verbal Fluency of animals (VFT-a), Phonological Verbal Fluency of letter P (VFT-p), Digit Span Test (DST), the Clock Drawing Test (CDT), and the Short Form-36 Health Survey (SF36-HRQL test). Dietary iron intake did not influence neuropsychological function or quality of life. However, anemia and lower levels of anemia markers were associated with worse scores in all neurophysiological and SF36-HRQL tests overall, but were especially clear in the MMSE, TMT-B (cognitive flexibility), and the physical component of the SF36-HRQL test. The relationships between anemia and diminished performance in the TMT-A/B and VFT tasks were notably pronounced and statistically significant solely among participants with diabetes. In brief, anemia and reduced levels of anemia markers were linked to inferior cognitive function, worse scores in different domains of executive function, as well as a poorer physical, but not mental, component of quality of life. It was also suggested that the coexistence of diabetes in anemic patients may exacerbate this negative impact on cognition. Nevertheless, dietary iron intake showed no correlation with any of the outcomes. To make conclusive recommendations for clinical practice, our findings need to be thoroughly tested through methodologically rigorous studies that minimize the risk of reverse causality

    Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

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    Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson‚Äôs disease (PD) and Alzheimer‚Äôs disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aő≤42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

    Highly-parallelized simulation of a pixelated LArTPC on a GPU

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    The rapid development of general-purpose computing on graphics processing units (GPGPU) is allowing the implementation of highly-parallelized Monte Carlo simulation chains for particle physics experiments. This technique is particularly suitable for the simulation of a pixelated charge readout for time projection chambers, given the large number of channels that this technology employs. Here we present the first implementation of a full microphysical simulator of a liquid argon time projection chamber (LArTPC) equipped with light readout and pixelated charge readout, developed for the DUNE Near Detector. The software is implemented with an end-to-end set of GPU-optimized algorithms. The algorithms have been written in Python and translated into CUDA kernels using Numba, a just-in-time compiler for a subset of Python and NumPy instructions. The GPU implementation achieves a speed up of four orders of magnitude compared with the equivalent CPU version. The simulation of the current induced on 10^3 pixels takes around 1 ms on the GPU, compared with approximately 10 s on the CPU. The results of the simulation are compared against data from a pixel-readout LArTPC prototype

    Poesía de sátira política y clandestina del Siglo de Oro. Antología esencial. Volumen I. Reinados de Felipe III y Felipe IV

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    En el marco del proyecto de investigaci√≥n "La burla como diversi√≥n y arma social en el Siglo de Oro (II). Poes√≠a pol√≠tica y clandestina. Recuperaci√≥n patrimonial y contexto hist√≥rico y cultural" (AEI/FEDER, UE, PID2020-116009GB-I00), del Ministerio de Ciencia e Innovaci√≥n (MICINN) del Gobierno de Espa√Īa, este volumen aborda el corpus correspondiente a los reinados de Felipe III y Felipe IV, ampliando sustancialmente el material disponible hasta el momento del abundante repertorio de la poes√≠a clandestina y de s√°tira pol√≠tica del Siglo de Oro. Incluye esta entrega 381 poemas procedentes de numerosos manuscritos, acompa√Īados de un aparato de notas que intenta aclarar las claves complejas de sus alusiones sat√≠ricas y precedidos de un estudio introductorio en el que, adem√°s de establecerse el estado de la cuesti√≥n sobre la materia, se ofrecen reflexiones te√≥ricas sobre los criterios y retos de edici√≥n de este dif√≠cil y fascinante corpus de enorme inter√©s literario, hist√≥rico, social y cultural

    1216P A spectroscopic liquid biopsy for the earlier detection of multiple cancer types

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    Background Employing a rapid liquid biopsy platform that can support clinicians in the diagnosis of different cancers, particularly for patients who develop cancers not targeted in current screening programs, would cause a paradigm shift in cancer diagnostics. Current liquid biopsies focus on single tumor derived biomarkers, such as circulating tumor DNA (ctDNA), which limits test sensitivity, especially for early-stage cancers that do not shed enough genetic material. Methods The Dxcover¬ģ Cancer Liquid Biopsy has been assessed upon its ability to predict individual cancers in organ-specific classifications: brain, breast, colorectal, kidney, lung, ovarian, pancreatic, and prostate cancer. The test uses Fourier transform infrared (FTIR) spectroscopy to build spectral profiles of serum samples, and machine learning algorithms to predict disease status. We also made a further exploratory evaluation of the ability to differentiate the signature from any one of the 8 cancers from non-cancer patient samples. We assessed the test performance when the cancer samples were grouped together to mimic patients with non-specific symptoms where the cancer site was uncertain. Additionally, we have examined non-generative data augmentation methods to improve machine learning performance. Results Area under the receiver operating characteristic curve (AUROC) values were calculated for 8 cancer types v symptomatic non-cancer controls: most classifiers achieved AUROC values above 0.85. The cancer v asymptomatic non-cancer classification detected 64% of stage I cancers when specificity was 99% (overall sensitivity 57%). When tuned for higher sensitivity, this model identified 99% of stage I cancers (with specificity 59%). For the colorectal cancer dataset, data augmentation using a WGAN led to an increase in AUROC from 0.91 to 0.96, demonstrating the impact data augmentation can have on deep learning performance, which could be useful when the amount of real data available for model training is limited

    Aspects of microbial communities in peatland carbon cycling under changing climate and land use pressures

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    This is the final version. Available on open access from the Finnish Peatland Society via the DOI in this record.‚ÄĮGlobally, major efforts are being made to restore peatlands to maximise their resilience to anthropogenic climate change, which puts continuous pressure on peatland ecosystems and modifies the geography of the environmental envelope that underpins peatland functioning. A probable effect of climate change is reduction in the waterlogged conditions that are key to peatland formation and continued accumulation of carbon (C) in peat. C sequestration in peatlands arises from a delicate imbalance between primary production and decomposition, and microbial processes are potentially pivotal in regulating feedbacks between environmental change and the peatland C cycle. Increased soil temperature, caused by climate warming or disturbance of the natural vegetation cover and drainage, may result in reductions of long-term C storage via changes in microbial community composition and metabolic rates. Moreover, changes in water table depth alter the redox state and hence have broad consequences for microbial functions, including effects on fungal and bacterial communities especially methanogens and methanotrophs. This article is a perspective review of the effects of climate change and ecosystem restoration on peatland microbial communities and the implications for C sequestration and climate regulation. It is authored by peatland scientists, microbial ecologists, land managers and non-governmental organisations who were attendees at a series of three workshops held at The University of Manchester (UK) in 2019‚Äď2020. Our review suggests that the increase in methane flux sometimes observed when water tables are restored is predicated on the availability of labile carbon from vegetation and the absence of alternative terminal electron acceptors. Peatland microbial communities respond relatively rapidly to shifts in vegetation induced by climate change and subsequent changes in the quantity and quality of below-ground C substrate inputs. Other consequences of climate change that affect peatland microbial communities and C cycling include alterations in snow cover and permafrost thaw. In the face of rapid climate change, restoration of a resilient microbiome is essential to sustaining the climate regulation functions of peatland systems. Technological developments enabling faster characterisation of microbial communities and functions support progress towards this goal, which will require a strongly interdisciplinary approach.Natural Environment Research Council (NERC

    Manejo del ictus agudo. Tratamientos y cuidados específicos de enfermería en la Unidad de Ictus

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    Resumen: Objetivo: Proporcionar un conjunto de recomendaciones actualizadas y basadas en la evidencia disponible para el manejo del ictus agudo. Nuestro objetivo es proporcionar una base para el desarrollo de los protocolos internos de cada centro, sirviendo de referencia para los cuidados de enfermería. Métodos: Revisión de evidencias disponibles sobre los cuidados del ictus agudo. Se han consultado las guías nacionales e internacionales más recientes. Los niveles de evidencia y grados de recomendación se han basado en la clasificación del Centro de Medicina Basada en la Evidencia de Oxford. Resultados: Se describen la atención y los cuidados del ictus agudo en la fase prehospitalaria, el funcionamiento de código ictus, la atención por el equipo de ictus a la llegada al hospital, los tratamientos de reperfusión y sus limitaciones, el ingreso en la Unidad de Ictus, los cuidados de enfermería en la Unidad de Ictus y el alta hospitalaria. Conclusiones: Estas pautas proporcionan recomendaciones generales basadas en la evidencia actualmente disponible para guiar a los profesionales que atienden a pacientes con ictus agudo. En algunos casos, sin embargo, existen datos limitados demostrando la necesidad de continuar investigando sobre el manejo del ictus agudo. Abstract: Objective: This study provides a series of updated, evidence-based recommendations for the management of acute stroke. We aim to lay a foundation for the development of individual centres’ internal protocols, serving as a reference for nursing care. Methods: We review the available evidence on acute stroke care. The most recent national and international guidelines were consulted. Levels of evidence and degrees of recommendation are based on the Oxford Centre for Evidence-Based Medicine classification. Results: The study describes prehospital acute stroke care, the operation of the code stroke protocol, care provided by the stroke team upon the patient's arrival at hospital, reperfusion treatments and their limitations, admission to the stroke unit, nursing care in the stroke unit, and discharge from hospital. Conclusions: These guidelines provide general, evidence-based recommendations to guide professionals who care for patients with acute stroke. However, limited data are available on some aspects, showing the need for continued research on acute stroke management

    Poesía de sátira política y clandestina del Siglo de Oro. Antología esencial. Volumen I. Reinados de Felipe III y Felipe IV

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    En el marco del proyecto de investigaci√≥n "La burla como diversi√≥n y arma social en el Siglo de Oro (II). Poes√≠a pol√≠tica y clandestina. Recuperaci√≥n patrimonial y contexto hist√≥rico y cultural" (AEI/FEDER, UE, PID2020-116009GB-I00), del Ministerio de Ciencia e Innovaci√≥n (MICINN) del Gobierno de Espa√Īa, este volumen aborda el corpus correspondiente a los reinados de Felipe III y Felipe IV, ampliando sustancialmente el material disponible hasta el momento del abundante repertorio de la poes√≠a clandestina y de s√°tira pol√≠tica del Siglo de Oro. Incluye esta entrega 381 poemas procedentes de numerosos manuscritos, acompa√Īados de un aparato de notas que intenta aclarar las claves complejas de sus alusiones sat√≠ricas y precedidos de un estudio introductorio en el que, adem√°s de establecerse el estado de la cuesti√≥n sobre la materia, se ofrecen reflexiones te√≥ricas sobre los criterios y retos de edici√≥n de este dif√≠cil y fascinante corpus de enorme inter√©s literario, hist√≥rico, social y cultural

    583P A rapid blood test for the earlier detection of colorectal cancer

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    Background The detection of colorectal cancer (CRC) in early stages can enable the removal of pre-cancerous lesions and allow earlier treatment. Most CRCs develop from adenomas, with ‚Äúadvanced‚ÄĚ adenoma (AA) considered to be clinically relevant precursor of CRC. Screening for CRC is recommended for average-risk adults using faecal immunochemical testing (FIT), but the performance of FIT is limited. FIT reportedly has false positive rate of ‚ąľ93%, and ‚ąľ10% of CRC diagnoses have a negative FIT result. Moreover, the sensitivity for detecting AA is only 24%, highlighting the need for alternative strategies. Methods The Dxcover¬ģ Colorectal Cancer Liquid Biopsy is a spectroscopic test that interrogates a blood sample with infrared light and generates a distinctive signature that represents the whole biomolecular profile of the sample. Patient samples (n=296) were retrospectively collected for this discovery study, and the full cohort consisted of 100 CRC, 99 adenoma (A) and 97 colonoscopy screening controls with a non-cancer (NC) diagnosis. Machine learning algorithms have been developed with the resultant spectral profiles to predict CRC and AA. Feature importance analysis has also been carried out to identify the spectral regions found to be most significant for each classification. Results The CRC v NC model achieved an area under the receiver operating characteristic curve (AUROC) of 0.93. At 90% specificity, the overall CRC sensitivity was 80%, and the detection rates were consistent across stages: 83% (I), 73% (II), 76% (III), and 100% (IV). The CRC+A v NC model reported an AUROC of 0.88, and at 90% specificity, the overall CRC sensitivity was 78%. The test successfully detected 83% of stage I, 73% of stage II, 76% of stage III and 87% of stage IV CRC. Furthermore, 59% of AA patients were identified with this classifier, which is greater than the current performance levels of FIT. Conclusions A rapid blood test that is sensitive to AA and early-stage CRC could substantially improve patient outcomes. This liquid biopsy can be fine-tuned to give a different balance of sensitivity and specificity depending on international healthcare markets. Current screening programmes have addressable shortcomings, and the emergence of new technologies is essential to support earlier CRC detection
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