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Multimodal machine learning to predict surgical site infection with healthcare workload impact assessment
No full textRemote monitoring is essential for healthcare digital transformation, however, this poses greater burdens on healthcare providers to review and respond as the data collected expands. This study developed a multimodal neural network to automate assessments of patient-generated data from remote postoperative wound monitoring. Two interventional studies including adult gastrointestinal surgery patients collected wound images and patient-reported outcome measures (PROMs) for 30-days postoperatively. Neural networks for PROMs and images were combined to predict surgical site infection (SSI) diagnosis within 48 h. The multimodal neural network model to predict confirmed SSI within 48 h remained comparable to clinician triage (0.762 [0.690-0.835] vs 0.777 [0.721-0.832]), with an excellent performance on external validation. Simulated usage indicated an 80% reduction in staff time (51.5 to 9.1 h) without compromising diagnostic accuracy. This multimodal approach can effectively support remote monitoring, alleviating provider burden while ensuring high-quality postoperative care.</p
Ferdinand de Saussure, the post-structuralist
No full textUnderstanding the linguistic work of earlier times demands that it be read in the context of when and why it was written. This effort is both aided and impeded by our habit of packaging the past into periods and doctrines that entail inevitable oversimplifications and distortions. This paper contends that structuralism conceived in such a distorted way – including the view that we are supposedly “post” it. Inspired by a student who referred to Saussure in an exam as a post-structuralist, I take up the case for seeing him as exactly that, in terms of how we generally conceive of structuralism, with a view to improving our understanding of what structuralist linguistics was – indeed, perhaps still is
Charitable giving responses to education budgets
Get PDFDo changes in government spending affect voluntary contributions to those recipients? We examine how changes in K-12 education budgets impact donations to teachers using data from DonorsChoose.org, an online crowdfunding platform for public school teachers to raise money. We find a positive correlation between budgets and voluntary contributions when not accounting for their endogenous relationship. Estimates using instrumental variables show evidence for crowd-out of private giving, though the magnitudes are small relative to spending and do not meaningfully offset budget changes. These results are driven entirely by teachers' posting of requests
Insulin receptor variants: extending the traditional Mendelian spectrum
Get PDFPurpose: INSR encodes the insulin receptor, the essential entrainer of growth and metabolism to nutritional cues. INSR variants cause a spectrum of monogenic insulin resistance (IR) syndromes, namely type A insulin resistance, Rabson-Mendenhall (RMS), and Donohue (DS) syndromes. However, no large cohort studies focused on variant classification and its diagnostic value have been described.Methods: This multicentric cohort study included 73 patients carrying INSR variants, referred for IR by 52 centers from six countries. Variants were classified using new bioinformatic toolsrelying on different prediction mechanisms, and the American College of Medical Genetics and Genomics (ACMG) guidelines.Results: Besides expanding the INSR mutational spectrum, this study suggested a semi-dominant inheritance in several DS/RMS families. Questioning strictly Mendelian inheritance, heterozygous loss-of-function (LoF) variants were mostly found in overweight patients, with a higher LoF frequency in IR patients than in the general population (OR: 5.77). Diagnostic challenges arose when trying to refine classification criteria for variants of uncertainsignificance. Among the variant effect predictors assessed, MISTIC and AlphaMissense outperformed REVEL.Conclusion: The spectrum of INSR-related disorders extends beyond traditional entities. Heterozygous INSR LoF variants may increase IR susceptibility. International collaboration and functional assays are needed to drive precision medicine forward.<br/
Optimization of Cyclophilin B-Targeted Tri-vector Inhibitors for Novel MASH Treatments
Get PDFCyclophilins have been implicated in the pathophysiology of metabolic dysfunction-associated steatohepatitis (MASH).Pharmacological inhibition of the cyclophilin B isoform has the potential to attenuate liver fibrosis in MASH, but current cyclophilin inhibitors in clinical trials lack isoform selectivity. We previously reported the novel tri-vector small-molecule inhibitor 1 that exhibited improved subtype selectivity by simultaneously engaging three pockets on the surface of cyclophilins. Here, we present structure−activity relationships that address genotoxicity concerns, enhance subtype selectivity, improve pharmaceutical properties, and demonstrate strong efficacy in a MASH cellular model. Lead compound 11 is a potent cyclophilin B inhibitor with an encouraging pharmacokinetic profile suitable for further development
Plasmodium falciparum induces T cell tolerance that is associated with decreased disease severity upon reinfection
Get PDFImmunity to severe malaria is acquired quickly, operates independently of pathogen load, and represents a highly effective form of disease tolerance. The mechanism that underpins tolerance remains unknown. We used a human rechallenge model of falciparum malaria in which healthy adult volunteers were infected three times over a 12 mo period to track the development of disease tolerance in real-time. We found that parasitemia triggered a hardwired innate immune response that led to systemic inflammation, pyrexia, and hallmark symptoms of clinical malaria across the first three infections of life. In contrast, a single infection was sufficient to reprogram T cell activation and reduce the number and diversity of effector cells upon rechallenge. Crucially, this did not silence stem-like memory cells but instead prevented the generation of cytotoxic effectors associated with autoinflammatory disease. Tolerized hosts were thus able to prevent collateral tissue damage in the absence of antiparasite immunity.</p
Work hours and amenity trade-offs
Get PDFWe present a compensating wage differentials model that incorporates complementarity and substitutability in firms' provision of amenities and workers' preferences for them. These interactions help explain why some amenities tend to be bundled, while others are more often traded off. Our empirical analysis examines amenity substitution in the US labor market using data from the National Longitudinal Survey of Youth 1997 cohort. We highlight how shorter or more flexible total work hours are traded off with other workplace amenities. Our findings suggest that women may need to forgo amenities they value to secure shorter, more flexible work hours
Hacia un análisis del lenguaje inclusivo desde una perspectiva glotopolítica
Get PDFLa lengua española parece encontrarse ante un proceso de evolución relacionado con un interés por potenciar una comunicación más inclusiva e igualitaria. Este parte de una serie de propuestas que empezaron cuestionando el uso del masculino genérico como género gramatical no marcado y desde las que se ha desafiado la norma a través de distintas estrategias lingüísticas que conviven en la lengua oral y en la escrita, y cuyo éxito y efectos aún se desconocen. Debido el impacto que tiene este fenómeno en la sociedad, que busca dar visibilidad a distintos tipos de personas y colectivos de forma más igualitaria, resulta de interés documentarlo y explorarlo desde distintos ángulos y enfoques. Para ello, tras presentar la situación actual del debate en torno al lenguaje inclusivo en español, argumentamos que puede resultar de interés adoptar una perspectiva glotopolítica como punto de partida para comprender con profundidad el origen y los fenómenos lingüísticos utilizados en la actualidad para la representación del género en español, ya que la glotopolítica facilita el examen de fenómenos en cuya configuración confluyen lengua y política. Desde este enfoque, es posible evaluar de manera crítica e interdisciplinar los aspectos lingüísticos, ideológicos y pedagógicos que intervienen en las propuestas existentes sobre el lenguaje inclusivo. Exploramos asimismo la alineación de esta perspectiva con los objetivos de descolonización y las agendas de inclusión, diversidad y equidad que en la actualidad se están promoviendo desde distintas instituciones y presentamos algunas propuestas recientes en el ámbito de la educación lingüística
Integrated functional genomic analysis identifies regulatory variants underlying a major QTL for disease resistance in European sea bass
Get PDFBACKGROUND: Viral nervous necrosis (VNN) is an important viral disease threatening global aquaculture sustainability and affecting over 50 farmed and ecologically important fish species. A major QTL for resistance to VNN has been previously detected in European sea bass, but the underlying causal gene(s) and mutation(s) remain unknown. To identify the mechanisms and genetic factors underpinning resistance to VNN in European sea bass, we employed integrative analyses of multiple functional genomics assays in European sea bass.RESULTS: The estimated heritability of VNN resistance was high (h2 ~ 0.40), and a major QTL explaining up to 38% of the genetic variance of the trait was confirmed on chromosome 3, with individuals with the resistant QTL genotype showing a 90% survivability against a VNN outbreak. Whole-genome resequencing analyses narrowed the location of this QTL to a small region containing 4 copies of interferon alpha inducible protein 27-like 2A (IFI27L2A) genes, and one copy of the interferon alpha inducible protein 27-like 2 (IFI27L2) gene. RNA sequencing revealed a clear association between the QTL genotype and the expression of two of the IFI27L2A genes, and the IFI27L2 gene. Integration with chromatin accessibility and histone modification data pinpointed two SNPs in active regulatory regions of two of these genes (IFI27L2A and IFI27L2), and transcription factor binding site gains for the resistant alleles were predicted. These alleles, particularly the SNP variant CHR3:10,077,301, exhibited higher frequencies (0.55 to 0.77) in Eastern Mediterranean Sea bass populations, which show considerably higher levels of resistance to VNN, as compared to susceptible West Mediterranean and Atlantic populations (0.15-0.25).CONCLUSIONS: The SNP variant CHR3:10,077,301, through modulation of IFI27L2 and IFI27L2A genes, is likely the causative mutation underlying resistance to VNN in European sea bass. This is one of the first causative mutations discovered for disease resistance traits in fish and paves the way for marker-assisted selection as well as biotechnological approaches to enhance resistance to VNN in European sea bass and other susceptible species.</p
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