A framework for assessing the lifetime economic burden of congenital cytomegalovirus in the United States

Background: In the United States (US), congenital cytomegalovirus infection (cCMVi) is a major cause of permanent disabilities and the most common etiology of non-genetic sensorineural hearing loss. Evaluations of prevention strategies will require estimates of the economic implications of cCMVi. We aimed to develop a conceptual framework to characterize the lifetime economic burden of cCMVi in the US and to use that framework to identify data gaps. Methods: Direct health care, direct non-health care, indirect, and intangible costs associated with cCMVi were considered. An initial framework was constructed based on a targeted literature review, then validated and refined after consultation with experts. Published costs were identified and used to populate the framework. Data gaps were identified. Results: The framework was constructed as a chance tree, categorizing clinical event occurrence to form patient profiles associated with distinct economic trajectories. The distribution and magnitude of costs varied by patient life stage, cCMVi diagnosis, severity of impairment, and developmental delays/disabilities. Published studies could not fully populate the framework. The literature best characterized direct health care costs associated with the birth period. Gaps existed for direct non-health care, indirect, and intangible costs, as well as health care costs associated with adult patients and those severely impaired. Conclusions: Data gaps exist concerning the lifetime economic burden of cCMVi in the US. The conceptual framework provides the basis for a research agenda to address these gaps. Understanding the full lifetime economic burden of cCMVi would inform clinicians, researchers, and policymakers, when assessing the value of cCMVi interventions

SCHISTOX: An individual based model for the epidemiology and control of schistosomiasis.

A stochastic individual based model, SCHISTOX, has been developed for the study of schistosome transmission dynamics and the impact of control by mass drug administration. More novel aspects that can be investigated include individual level adherence and access to treatment, multiple communities, human sex population dynamics, and implementation of a potential vaccine. Many of the model parameters have been estimated within previous studies and have been shown to vary between communities, such as the age-specific contact rates governing the age profiles of infection. However, uncertainty remains as there are wide ranges for certain parameter values and a few remain relatively unknown. We analyse the model dynamics by parameterizing it with published parameter values. We also discuss the development of SCHISTOX in the form of a publicly available open-source GitHub repository. The next key development stage involves validating the model by calibrating to epidemiological data

Suicide Attempts Among a Cohort of Transgender and Gender Diverse People

INTRODUCTION: Transgender and gender diverse people often face discrimination and may experience disproportionate emotional distress that leads to suicide attempts. Therefore, it is essential to estimate the frequency and potential determinants of suicide attempts among transgender and gender diverse individuals. METHODS: Longitudinal data on 6,327 transgender and gender diverse individuals enrolled in 3 integrated healthcare systems were analyzed to assess suicide attempt rates. Incidence was compared between transmasculine and transfeminine people by age and race/ethnicity and according to mental health status at baseline. Cox proportional hazards models examined rates and predictors of suicide attempts during follow-up. Data were collected in 2016, and analyses were conducted in 2019. RESULTS: During follow-up, 4.8% of transmasculine and 3.0% of transfeminine patients had at least 1 suicide attempt. Suicide attempt rates were more than 7 times higher among patients aged45 years, more than 3 times higher among patients with previous history of suicide ideation or suicide attempts than among those with no such history, and 2-5 times higher among those with 1-2 mental health diagnoses and more than 2 mental health diagnoses at baseline than among those with none. CONCLUSIONS: Among transgender and gender diverse individuals, younger people, people with previous suicidal ideation or attempts, and people with multiple mental health diagnoses are at a higher risk for suicide attempts. Future research should examine the impact of gender-affirming healthcare use on the risk of suicide attempts and identify targets for suicide prevention interventions among transgender and gender diverse people in clinical settings

Early blood glucose profile and neurodevelopmental outcome at two years in neonatal hypoxic-ischaemic encephalopathy

Background: To examine the blood glucose profile and the relationship between blood glucose levels and neurodevelopmental outcome in term infants with hypoxic-ischaemic encephalopathy. Methods: Blood glucose values within 72 hours of birth were collected from 52 term infants with hypoxic-ischaemic encephalopathy. Hypoglycaemia [ 150 mg/dL (8.3 mmol/L)] were correlated to neurodevelopmental outcome at 24 months of age. Results: Four fifths of the 468 blood samples were in the normoglycaemic range (392/468:83.8%). Of the remaining 76 samples, 51.3% were in the hypoglycaemic range and (48.7%) were hyperglycaemic. A quarter of the hypoglycaemic samples (28.2%:11/39) and a third of the hyperglycaemic samples (32.4%:12/37) were recorded within the first 30 minutes of life. Mean (SD) blood glucose values did not differ between infants with normal and abnormal outcomes [4.89(2.28) mmol/L and 5.02(2.35) mmol/L, p value = 0.15] respectively. In term infants with hypoxic-ischaemic encephalopathy, early hypoglycaemia (between 0-6 hours of life) was associated with adverse outcome at 24 months of age [OR = 5.8, CI = 1.04-32)]. On multivariate analysis to adjust for grade of HIE this association was not statistically significant. Late hypoglycaemia (6-72 hours of life) was not associated with abnormal outcome [OR = 0.22, CI (0.04-1.14)]. The occurrence of hyperglycaemia was not associated with adverse outcome. Conclusion: During the first 72 hours of life, blood glucose profile in infants with hypoxic-ischaemic encephalopathy varies widely despite a management protocol. Early hypoglycaemia (0-6 hours of life) was associated with severe HIE, and thereby; adverse outcome

The Third Fermi Large Area Telescope Catalog of Gamma-ray Pulsars

We present 294 pulsars found in GeV data from the Large Area Telescope (LAT) on the Fermi Gamma-ray Space Telescope. Another 33 millisecond pulsars (MSPs) discovered in deep radio searches of LAT sources will likely reveal pulsations once phase-connected rotation ephemerides are achieved. A further dozen optical and/or X-ray binary systems co-located with LAT sources also likely harbor gamma-ray MSPs. This catalog thus reports roughly 340 gamma-ray pulsars and candidates, 10% of all known pulsars, compared to $\leq 11$ known before Fermi. Half of the gamma-ray pulsars are young. Of these, the half that are undetected in radio have a broader Galactic latitude distribution than the young radio-loud pulsars. The others are MSPs, with 6 undetected in radio. Overall, >235 are bright enough above 50 MeV to fit the pulse profile, the energy spectrum, or both. For the common two-peaked profiles, the gamma-ray peak closest to the magnetic pole crossing generally has a softer spectrum. The spectral energy distributions tend to narrow as the spindown power $\dot E$ decreases to its observed minimum near $10^{33}$ erg s$^{-1}$, approaching the shape for synchrotron radiation from monoenergetic electrons. We calculate gamma-ray luminosities when distances are available. Our all-sky gamma-ray sensitivity map is useful for population syntheses. The electronic catalog version provides gamma-ray pulsar ephemerides, properties and fit results to guide and be compared with modeling results.Comment: 142 pages. Accepted by the Astrophysical Journal Supplemen

Creative destruction in science

Drawing on the concept of a gale of creative destruction in a capitalistic economy, we argue that initiatives to assess the robustness of findings in the organizational literature should aim to simultaneously test competing ideas operating in the same theoretical space. In other words, replication efforts should seek not just to support or question the original findings, but also to replace them with revised, stronger theories with greater explanatory power. Achieving this will typically require adding new measures, conditions, and subject populations to research designs, in order to carry out conceptual tests of multiple theories in addition to directly replicating the original findings. To illustrate the value of the creative destruction approach for theory pruning in organizational scholarship, we describe recent replication initiatives re-examining culture and work morality, working parents\u2019 reasoning about day care options, and gender discrimination in hiring decisions. Significance statement It is becoming increasingly clear that many, if not most, published research findings across scientific fields are not readily replicable when the same method is repeated. Although extremely valuable, failed replications risk leaving a theoretical void\u2014 reducing confidence the original theoretical prediction is true, but not replacing it with positive evidence in favor of an alternative theory. We introduce the creative destruction approach to replication, which combines theory pruning methods from the field of management with emerging best practices from the open science movement, with the aim of making replications as generative as possible. In effect, we advocate for a Replication 2.0 movement in which the goal shifts from checking on the reliability of past findings to actively engaging in competitive theory testing and theory building. Scientific transparency statement The materials, code, and data for this article are posted publicly on the Open Science Framework, with links provided in the article

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Gut fermentation of dietary fibres: physico-chemistry of plant cell walls and implications for health

The majority of dietary fibre (DF) originates from plant cell walls. Chemically, DF mostly comprise carbohydrate polymers, which resist hydrolysis by digestive enzymes in the mammalian small intestine, but can be fermented by large intestinal bacteria. One of the main benefits of DF relate to its fermentability, which affects microbial diversity and function within the gastro-intestinal tract (GIT), as well as the by-products of the fermentation process. Much work examining DF tends to focus on various purified ingredients, which have been extracted from plants. Increasingly, the validity of this is being questioned in terms of human nutrition, as there is evidence to suggest that it is the actual complexity of DF which affects the complexity of the GIT microbiota. Here, we review the literature comparing results of fermentation of purified DF substrates, with whole plant foods. There are strong indications that the more complex and varied the diet (and its ingredients), the more complex and varied the GIT microbiota is likely to be. Therefore, it is proposed that as the DF fermentability resulting from this complex microbial population has such profound effects on human health in relation to diet, it would be appropriate to include DF fermentability in its characterization-a functional approach of immediate relevance to nutrition

Whole fruit pulp (mango) and a soluble fibre (pectin) impact bacterial diversity and abundance differently within the porcine large intestine

Effects of diets including a fruit cell-wall matrix (mango) or a soluble cell-wall polymer (pectin), on the porcine large intestinal (LI) bacterial community were examined at the caecum (Cae), proximal (PC), mid- (MC), and distal colon (DC), investigating both bacterial composition and metabolic end-products. Pigs were fed one of three diets: Control based on wheat starch, and treatment diets where starch was partially substituted with either 15% mango pulp or 10% pectin. Fermentation end-products were significantly different between diets, and LI sites (P  Control > Pectin. Between diet groups, there were distinct community differences. Species abundance that differed per diet included Faecalibacterium prausnitzii (Pectin), and Lactobacillus mucosae (Mango). However, Mango promoted a more stable abundance of F. prausnitzii along the LI, while Pectin resulted in F. prausnitzii abundance being high proximally and low distally. This contrasted with the low fibre Control diet results, where F. prausnitzii was not detectable. This study has shown that although pectin can promote extensive fermentation early in the LI, more prolonged and beneficial effects in the distal LI, including greater microbial species diversity, occur when the diet includes plant material with complex intact plant cell-walls, such as from mango