A Bayesian approach to discrete multiple outcome network meta-analysis

In this paper we suggest a new Bayesian approach to network meta-analysis for the case of discrete multiple outcomes. The joint distribution of the discrete outcomes is modeled through a Gaussian copula with binomial marginals. The remaining elements of the hierarchial random effects model are specified in a standard way, with the logit of the success probabilities given by the sum of a baseline log-odds and random effects comparing the log-odds of each treatment against the reference and having a Gaussian distribution centered at the vector of pooled effects. An adaptive Markov Chain Monte Carlo algorithm is devised for running posterior inference. The model is applied to two datasets from Cochrane reviews, already analysed in two papers so to assess and compare its performance. We implemented the model in a freely available R package called netcopula

Chisini means and rational decision making: Equivalence of investment criteria

A plethora of tools are used for investment decisions and performance measurement, including Net Present Value (NPV), Internal Rate of Return (IRR), Profitability Index (PI), Modified Internal Rate of Return (MIRR), Average Accounting Rate of Return (AARR). All these and other known metrics are generally considered non-equivalent and some of them are regarded as unreliable or even naive. Building upon Magni (2010a, 2013)'s Average Internal Rate of Return (AIRR), we show that the notion of Chisini mean enables these tools to be used as rational decision criteria. Specifically, we focus on 11 metrics and show that, if properly used, they all provide equivalent accept-reject decisions and equivalent project rankings. Therefore, the intuitive notion of mean is the founding basis of investment decision criteria

Metal and dust evolution in ALMA REBELS galaxies: insights for future JWST observations

ALMA observations revealed the presence of significant amounts of dust in the first Gyr of Cosmic time. However, the metal and dust buildup picture remains very uncertain due to the lack of constraints on metallicity. JWST has started to reveal the metal content of high-redshift targets, which may lead to firmer constraints on high-redshift dusty galaxies evolution. In this work, we use detailed chemical and dust evolution models to explore the evolution of galaxies within the ALMA REBELS survey, testing different metallicity scenarios that could be inferred from JWST observations. In the models, we track the buildup of stellar mass by using non-parametric SFHs for REBELS galaxies. Different scenarios for metal and dust evolution are simulated by allowing different prescriptions for gas flows and dust processes. The model outputs are compared with measured dust scaling relations, by employing metallicity-dependent calibrations for the gas mass based on the [CII]158micron line. Independently of the galaxies metal content, we found no need for extreme dust prescriptions to explain the dust masses revealed by ALMA. However, different levels of metal enrichment will lead to different dominant dust production mechanisms, with stardust production dominant over other ISM dust processes only in the metal-poor case. This points out how metallicity measurements from JWST will significantly improve our understanding of the dust buildup in high-redshift galaxies. We also show that models struggle to reproduce observables such as dust-to-gas and dust-to-stellar ratios simultaneously, possibly indicating an overestimation of the gas mass through current calibrations, especially at high metallicities.Comment: 16 pages + appendices, 9 Figures, 1 Table. Resubmitted to MNRAS after moderate revisio

The ALMA REBELS Survey: Dust Continuum Detections at z > 6.5

We report 18 dust continuum detections ($\geq 3.3\sigma$) at $\sim88{\rm \mu m}$ and $158{\rm \mu m}$ out of 49 ultraviolet(UV)-bright galaxies ($M_{\rm UV} 6.5$, observed by the Cycle-7 ALMA Large Program, REBELS and its pilot programs. This has more than tripled the number of dust continuum detections known at $z>6.5$. Out of these 18 detections, 12 are reported for the first time as part of REBELS. In addition, 15 of the dust continuum detected galaxies also show a [CII]$_{\rm 158{\rm \mu m}}$ emission line, providing us with accurate redshifts. We anticipate more line emission detections from six targets (including three continuum detected targets) where observations are still ongoing. The dust continuum detected sources in our sample tend to have a redder UV spectral slope than the ones without a dust continuum detection. We estimate that all of the sources have an infrared (IR) luminosity ($L_{\rm IR}$) in a range of $3-8 \times 10^{11} L_\odot$, except for one with $L_{\rm IR} = 1.5^{+0.8}_{-0.5} \times 10^{12}\,L_{\odot}$. Their fraction of obscured star formation is significant at $\gtrsim 50\%$. Some of the dust continuum detected galaxies show spatial offsets ($\sim 0.5-1.5''$) between the rest-UV and far-IR emission peaks. These separations appear to have an increasing trend against an indicator that suggests spatially decoupled phases of obscured and unobscured star formation. REBELS offers the best available statistical constraints on obscured star formation in UV-bright, massive galaxies at $z > 6.5$.Comment: 17 pages, 9 figures, submitted to MNRA

Identifying phenotypic expansions for congenital diaphragmatic hernia plus (CDH+) using DECIPHER data.

Congenital diaphragmatic hernia (CDH) can occur in isolation or in conjunction with other birth defects (CDH+). A molecular etiology can only be identified in a subset of CDH cases. This is due, in part, to an incomplete understanding of the genes that contribute to diaphragm development. Here, we used clinical and molecular data from 36 individuals with CDH+ who are cataloged in the DECIPHER database to identify genes that may play a role in diaphragm development and to discover new phenotypic expansions. Among this group, we identified individuals who carried putatively deleterious sequence or copy number variants affecting CREBBP, SMARCA4, UBA2, and USP9X. The role of these genes in diaphragm development was supported by their expression in the developing mouse diaphragm, their similarity to known CDH genes using data from a previously published and validated machine learning algorithm, and/or the presence of CDH in other individuals with their associated genetic disorders. Our results demonstrate how data from DECIPHER, and other public databases, can be used to identify new phenotypic expansions and suggest that CREBBP, SMARCA4, UBA2, and USP9X play a role in diaphragm development

Aggressive vs. conservative phototherapy for infants with extremely low birth weight.

BACKGROUND: It is unclear whether aggressive phototherapy to prevent neurotoxic effects of bilirubin benefits or harms infants with extremely low birth weight (1000 g or less). METHODS: We randomly assigned 1974 infants with extremely low birth weight at 12 to 36 hours of age to undergo either aggressive or conservative phototherapy. The primary outcome was a composite of death or neurodevelopmental impairment determined for 91% of the infants by investigators who were unaware of the treatment assignments. RESULTS: Aggressive phototherapy, as compared with conservative phototherapy, significantly reduced the mean peak serum bilirubin level (7.0 vs. 9.8 mg per deciliter [120 vs. 168 micromol per liter], P\u3c0.01) but not the rate of the primary outcome (52% vs. 55%; relative risk, 0.94; 95% confidence interval [CI], 0.87 to 1.02; P=0.15). Aggressive phototherapy did reduce rates of neurodevelopmental impairment (26%, vs. 30% for conservative phototherapy; relative risk, 0.86; 95% CI, 0.74 to 0.99). Rates of death in the aggressive-phototherapy and conservative-phototherapy groups were 24% and 23%, respectively (relative risk, 1.05; 95% CI, 0.90 to 1.22). In preplanned subgroup analyses, the rates of death were 13% with aggressive phototherapy and 14% with conservative phototherapy for infants with a birth weight of 751 to 1000 g and 39% and 34%, respectively (relative risk, 1.13; 95% CI, 0.96 to 1.34), for infants with a birth weight of 501 to 750 g. CONCLUSIONS: Aggressive phototherapy did not significantly reduce the rate of death or neurodevelopmental impairment. The rate of neurodevelopmental impairment alone was significantly reduced with aggressive phototherapy. This reduction may be offset by an increase in mortality among infants weighing 501 to 750 g at birth. (ClinicalTrials.gov number, NCT00114543.

Metal and dust evolution in ALMA REBELS galaxies: insights for future JWST observations

Atacama Large Millimeter/submillimeter Array (ALMA) observations revealed the presence of significant amounts of dust in the first Gyr of Cosmic time. However, the metal and dust build-up picture remains very uncertain due to the lack of constraints on metallicity. JWST has started to reveal the metal content of high-redshift targets, which may lead to firmer constraints on high-redshift dusty galaxies evolution. In this work, we use detailed chemical and dust evolution models to explore the evolution of galaxies within the ALMA Reionization Era Bright Emission Line Survey (REBELS) survey, testing different metallicity scenarios that could be inferred from JWST observations. In the models, we track the build-up of stellar mass using non-parametric star formation histories for REBELS galaxies. Different scenarios for metal and dust evolution are simulated by allowing different prescriptions for gas flows and dust processes. The model outputs are compared with measured dust scaling relations, by employing metallicity-dependent calibrations for the gas mass based on the [C II] 158 μm line. Independently of the galaxies metal content, we found no need for extreme dust prescriptions to explain the dust masses revealed by ALMA. However, different levels of metal enrichment will lead to different dominant dust production mechanisms, with stardust production dominant over other interstellar medium dust processes only in the metal-poor case. This points out how metallicity measurements from JWST will significantly improve our understanding of the dust build-up in high-redshift galaxies. We also show that models struggle to reproduce observables such as dust-to-gas and dust-to-stellar ratios simultaneously, possibly indicating an overestimation of the gas mass through current calibrations, especially at high metallicities.MP, IDL, and SvdG acknowledge funding support from ERC starting grant 851622 DustOrigin. MP also thank Laura Sommovigo for providing data adopted in this paper. MR acknowledges financial support by the research projects AYA2017-84897-P and PID2020-113689GB-I00, financed by MCIN/AEI/10.13039/501100011033. PD acknowledges support from the NWO grant 016.VIDI.189.162 (ODIN) and from the European Commission’s and University of Groningen’s CO-FUND Rosalind Franklin programme. HSBA and HI acknowledge support from the NAOJ ALMA Scientific Research Grant Code 2021–19A. MA acknowledges support from FONDECYT grant 1211951 and ANID BASAL project FB210003. RB acknowledges support from an STFC Ernest Rutherford Fellowship (grant number ST/T003596/1). JH acknowledges support from the ERC Consolidator Grant 101088676 (VOYAJ) and the VIDI research programme with project number 639.042.611, which is (partly) financed by the Netherlands Organisation for Scientific Research (NWO).Peer reviewe

Macrophage entry mediated by HIV Envs from brain and lymphoid tissues is determined by the capacity to use low CD4 levels and overall efficiency of fusion

AbstractHIV infects macrophages and microglia in the central nervous system (CNS), which express lower levels of CD4 than CD4+ T cells in peripheral blood. To investigate mechanisms of HIV neurotropism, full-length env genes were cloned from autopsy brain and lymphoid tissues from 4 AIDS patients with HIV-associated dementia (HAD). Characterization of 55 functional Env clones demonstrated that Envs with reduced dependence on CD4 for fusion and viral entry are more frequent in brain compared to lymphoid tissue. Envs that mediated efficient entry into macrophages were frequent in brain but were also present in lymphoid tissue. For most Envs, entry into macrophages correlated with overall fusion activity at all levels of CD4 and CCR5. gp160 nucleotide sequences were compartmentalized in brain versus lymphoid tissue within each patient. Proline at position 308 in the V3 loop of gp120 was associated with brain compartmentalization in 3 patients, but mutagenesis studies suggested that P308 alone does not contribute to reduced CD4 dependence or macrophage-tropism. These results suggest that HIV adaptation to replicate in the CNS selects for Envs with reduced CD4 dependence and increased fusion activity. Macrophage-tropic Envs are frequent in brain but are also present in lymphoid tissues of AIDS patients with HAD, and entry into macrophages in the CNS and other tissues is dependent on the ability to use low receptor levels and overall efficiency of fusion

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe