HIV and Hepatitis C Mortality in Massachusetts, 2002–2011: Spatial Cluster and Trend Analysis of HIV and HCV Using Multiple Cause of Death

Background: Infectious diseases, while associated with a much smaller proportion of deaths than they were 50 years ago, still play a significant role in mortality across the state of Massachusetts. Most analysis of infectious disease mortality in the state only take into account the underlying cause of death, rather than contributing causes of death, which may not capture the full extent of mortality trends for infectious diseases such as HIV and the Hepatitis C virus (HCV). Methods: In this study we sought to evaluate current trends in infectious disease mortality across the state using a multiple cause of death methodology. We performed a mortality trend analysis, identified spatial clusters of disease using a 5-step geoprocessing approach and examined spatial-temporal clustering trends in infectious disease mortality in Massachusetts from 2002–2011, with a focus on HIV/AIDS and HCV. Results: Significant clusters of high infectious disease mortality in space and time throughout the state were detected through both spatial and space time cluster analysis. The most significant clusters occurred in Springfield, Worcester, South Boston, the Merrimack Valley, and New Bedford with other smaller clusters detected across the state. Multiple cause of death mortality rates were much higher than underlying cause mortality alone, and significant disparities existed across race and age groups. Conclusions: We found that our multi-method analyses, which focused on contributing causes of death, were more robust than analyses that focused on underlying cause of death alone. Our results may be used to inform public health resource allocation for infectious disease prevention and treatment programs, provide novel insight into the current state of infectious disease mortality throughout the state, and benefited from approaches that may more accurately document mortality trends

A classification model of homelessness using integrated administrative data: Implications for targeting interventions to improve the housing status, health and well-being of a highly vulnerable population

Homelessness is poorly captured in most administrative data sets making it difficult to understand how, when, and where this population can be better served. This study sought to develop and validate a classification model of homelessness. Our sample included 5,050,639 individuals aged 11 years and older who were included in a linked dataset of administrative records from multiple state-maintained databases in Massachusetts for the period from 2011-2015. We used logistic regression to develop a classification model with 94 predictors and subsequently tested its performance. The model had high specificity (95.4%), moderate sensitivity (77.8%) for predicting known cases of homelessness, and excellent classification properties (area under the receiver operating curve 0.94; balanced accuracy 86.4%). To demonstrate the potential opportunity that exists for using such a modeling approach to target interventions to mitigate the risk of an adverse health outcome, we also estimated the association between model predicted homeless status and fatal opioid overdoses, finding that model predicted homeless status was associated with a nearly 23-fold increase in the risk of fatal opioid overdose. This study provides a novel approach for identifying homelessness using integrated administrative data. The strong performance of our model underscores the potential value of linking data from multiple service systems to improve the identification of housing instability and to assist government in developing programs that seek to improve health and other outcomes for homeless individuals

How values and perceptions shape farmers' biodiversity management: insights from ten European countries

Farmers play a pivotal role in addressing biodiversity loss whilst maintaining food production. To rethink conservation in agricultural landscapes, it is crucial to understand their decisions regarding biodiversity and its management on the farms. In this study, we conducted 48 semi-structured interviews across ten European countries in 2021/22 to explore how farmers’ perceptions and valuations relate to their biodiversity management. Employing reflexive thematic analysis, we identified recurring patterns of shared meanings. Our findings underscore the profound influence of farmers’ biodiversity perceptions on their biodiversity management practices: 1) Narrow and targeted interventions were closely tied to instrumental values of biodiversity, whereas holistic management strategies were linked with recognising an inherent value of nature. 2) Targeted approaches were related to farmers’ interpretations of biodiversity as specific taxa and functions, relying on easily assessable and emotionally connoted indicators. 3) Holistic approaches aligned with a broader biodiversity concept and an emphasis on intricate functional relationships within ecosystems. 4) Actual decisions to implement measures were significantly constrained by perceived dependencies, namely production pathways, social dependencies, and landscape conditions. These findings raise a critical question about the prioritisation of ecocentric intrinsic versus anthropocentric instrumental values in conservation strategies. We propose an approach of ethical pluralism, acknowledging that instrumental values may provide practical solutions for certain challenges, while intrinsic values hold ethical significance, particularly in the context of complex or large-scale biodiversity conservation initiatives. Engaging in dialogue that accounts for diverse values will be essential for shaping effective and socially meaningful biodiversity conservation

Who are the visitors of the art museums: Particularities of the publics of the weekends at the Art Museum of Tigre (Argentina)

Saber quiénes son sus visitantes es una de las principales tareas de los museos en la actualidad, en la medida en que fluctúan entre ajustarse a las imposiciones del sistema capitalista y convertirse en instituciones democráticas y participativas. No obstante, este aspecto resulta aun más dificultoso en los museos de arte, en virtud de los atributos particulares de su estructura y actores. El presente trabajo tiene como objetivo aproximar algunos criterios que permitan conocer quiénes son los visitantes de los museos de arte creados en Argentina desde el inicio del nuevo milenio. Dada la magnitud del desafío, se procura, con el foco puesto en un caso particular, trazar algunos lineamientos sostenidos en los enfoques teórico-críticos aplicados a la museología y en los estudios de públicos. En cuanto a lo metodológico, se recurrió a un estudio de visitantes que apeló a orientaciones cuantitativas y cualitativas, realizado en el Museo de Arte de Tigre durante 2017, centrado en los públicos del fin de semana. Se considera que, al indagar los rasgos singulares de esta entidad patrimonial, pueden identificarse algunos indicios que permitan comenzar a trazar un perfil, tanto general como específico, de los visitantes de los museos de arte.Knowing who its visitors are is one of the main tasks of museums today, as they fluctuate between conforming to the impositions of the capitalist system and becoming democratic and participatory institutions. However, this aspect is even more difficult in the arts museums because of the particular attributes of their structure and its diverse actors. The present work has as main object to bring near some criteria that may allow to know who are the visitors of the art museums in Argentina since the beginning of the new millennium. Given the extent of the challenge, we’ll try, focusing in a particular case, draw some guidelines sustained in the theorical-critical approaches applied to museology and studies of the publics. In terms of methodology, a visitor study was carried out at the Tigre Art Museum in 2017, using both quantitative and qualitative guidelines, focusing on weekend audiences. It is considered that, when we question the singularities of this entity, there are some indications that a general and specific profile of visitors to art museums can begin to be identified.Saber quem são seus visitantes é uma das principais tarefas dos museus na atualidade, na medida em que flutuam entre amoldar-se às imposições do sistema capitalista e converter-se em instituições democráticas e participativas. Não obstante, este aspecto resulta ainda mais dificultoso nos museus de arte, devido aos atributos particulares de sua estrutura e atores. O presente trabalho tem por objetivo aproximar alguns critérios que permitam conhecer quem são os visitantes dos museus de arte criados na Argentina desde o início do novo milênio. Dada a magnitude do desafio, e com o foco posto em um caso particular, buscou-se traçar alguns lineamentos sustentados nos enfoques teórico-críticos aplicados à museologia e nos estudos de públicos. Quanto à metodologia, a pesquisa teve como base um estudo de visitantes que apelou a orientações quantitativas e qualitativas, realizado no Museu de Arte de Tigre durante o ano de 2017, focado nos públicos de fim de semana. Considera-se que, ao indagarmos os traços singulares desta entidade, podem ser identificados alguns indícios que permitam começar a esboçar um perfil, tanto geral quanto específico, dos visitantes dos museus de arte.Fil: Panozzo Zenere, Alejandra Gabriela. Universidad Nacional de Rosario. Facultad de Ciencias Políticas y Relaciones Internacionales. Instituto de Investigaciones. Centro de Investigaciones en Mediatizaciones; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentin

CMB-S4: Forecasting Constraints on Primordial Gravitational Waves

CMB-S4---the next-generation ground-based cosmic microwave background (CMB) experiment---is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the Universe, from the highest energies at the dawn of time through the growth of structure to the present day. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semi-analytic projection tool, targeted explicitly towards optimizing constraints on the tensor-to-scalar ratio, $r$, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2--3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments given a desired scientific goal. To form a closed-loop process, we couple this semi-analytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for $r > 0.003$ at greater than $5\sigma$, or, in the absence of a detection, of reaching an upper limit of $r < 0.001$ at $95\%$ CL.Comment: 24 pages, 8 figures, 9 tables, submitted to ApJ. arXiv admin note: text overlap with arXiv:1907.0447

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

CMB-S4: Forecasting Constraints on Primordial Gravitational Waves

Abstract: CMB-S4—the next-generation ground-based cosmic microwave background (CMB) experiment—is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the universe. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2–3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments, given a desired scientific goal. To form a closed-loop process, we couple this semianalytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than 5σ, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL

Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy.

We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities