Immune reconstitution syndrome in HIV: validating a case definition and identifying clinical predictors in persons initiating antiretroviral therapy

Background: Clinical deterioration after initiation of antiretroviral therapy may result from restored immunity. There is no standard clinical definition for immune reconstitution syndrome. The objectives of this study were to validate a proposed definition and to identify factors predictive of immune reconstitution syndrome. Methods: This was a retrospective case-control study from an academic university medical practice. Cases were matched to ⩾2 control subjects by CD4+ cell count at the time of initiation of antiretroviral therapy. Cases and “mock cases” were blindly reviewed by 2 human immunodeficiency virus (HIV) experts. Results: Twenty possible cases of immune reconstitution syndrome were identified; HIV experts excluded all cases of herpes zoster (shingles), with agreement on real and mock cases of 92%. For 14 confirmed case patients (compared with 40 control subjects), immune reconstitution syndrome was associated with a higher number of prior opportunistic infections (P = .003) and higher CD8+ cell counts at baseline (P = .05) and at week 12 (P = .02). Immune reconstitution syndrome was associated with lower baseline levels of alanine aminotransferase (P = .05) and hemoglobin (P = .02). On multivariate analysis, the number of prior opportunistic infections (odds ratio, 2.7; P = .007) and lower hemoglobin level at baseline (odds ratio, 0.8; P = .003) were independently associated with development of immune reconstitution syndrome. A predictive model was defined by classification and regression tree analysis with a sensitivity and specificity of 78.57% and 87.50%, respectively, for an importance score of ⩾4 (on a scale of 0.0 to 100.0), and 92.86% and 80.00%, respectively, for a score of ⩾2, using the number of prior opportunistic infections, CD8+ cell count, and hemoglobin level. Conclusions: A standard definition for immune reconstitution syndrome is possible. Patients with a greater severity of illness at initiation of antiretroviral therapy are at risk for immune reconstitution syndrome. The model defined by classification and regression tree analysis may provide a basis for risk stratification before initiation of antiretroviral therapy

Effects of Star Formation Stochasticity on the Ly-alpha & Lyman Continuum Emission from Dwarf Galaxies during Reionization

Observations of distant galaxies play a key role in improving our understanding of the Epoch of Reionization (EoR). The observed Ly-alpha emission line strength - quantified by its restframe equivalent width (EW) - provides a valuable diagnostic of stellar populations and dust in galaxies during and after the EoR. In this paper we quantify the effects of star formation stochasticity on the predicted Ly-alpha EW in dwarf galaxies, using the publicly available code SLUG ('Stochastically Light Up Galaxies'). We compute the number of hydrogen ionizing photons, as well as flux in the Far UV for a set of models with star formation rates (SFR) in the range 10-3-1 Msol/yr. From these fluxes we compute the luminosity, L-alpha, and the EW of the Ly-alpha line. We find that stochasticity alone induces a broad distribution in L-alpha and EW at a fixed SFR, and that the widths of these distributions decrease with increasing SFR. We parameterize the EW probability density function (PDF) as an SFR-dependent double power law. We find that it is possible to have EW as low as ~EW0/4 and as high as ~3 times the EW0, where EW0 denotes the expected EW in the absence of stochasticity. We argue that stochasticity may therefore be important when linking drop-out and narrow-band selected galaxies, when identifying population III galaxies, and that it may help to explain the large EW (EW > 100 - 200 A) observed for a fraction of Ly-alpha- selected galaxies. Finally, we show that stochasticity can also affect the inferred escape fraction of ionizing photons from galaxies. In particular, we argue that stochasticity may simultaneously explain the observed anomalous ratios of the Lyman continuum flux density to the (non-ionizing) UV continuum density in so-called Lyman-Bump galaxies at z = 3.1, as well as the absence of such objects among a sample of z = 1.3 drop-out galaxies.Comment: 9 pages, 4 figures, accepted for publication in MNRA

Impact of COVID-19 on accident and emergency attendances and emergency and planned hospital admissions in Scotland:an interrupted timeseries analysis

Funding: This analysis is part of the Early Assessment of COVID-19 epidemiology and Vaccine/anti-viral Effectiveness (EAVE II) study. EAVE II is funded by the Medical Research Council (MR/R008345/1) with the support of BREATHE -The Health Data Research Hub for Respiratory Health [MC_PC_19004], which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. Additional support has been provided through the Scottish Government DGHealth and Social Care. HRS is supported by the Medical Research Council [MR/R008345/1].Objectives: Following the outbreak of SARS-CoV-2, health systems and the populations who use them have faced unprecedented challenges. We aimed to measure the impact of COVID-19 on the uptake of hospital-based care at a national level. Design: The study period (weeks ending 05 January to 28 June 2020) encompassed the pandemic announcement by the World Health Organization (WHO) and the initiation of the UK lockdown. We undertook an interrupted time-series analysis to evaluate the impact of these events on hospital services at a national level and across demographics, clinical specialties and NHS Health Boards. Setting: Scotland, UK. Participants: Patients receiving hospital care from NHS Scotland.Main outcome measures: A&E attendances, and emergency and planned hospital admissions measured using the relative change of weekly counts in 2020 to the averaged counts for equivalent weeks in 2018 and 2019. Results: Before the pandemic announcement, the uptake of hospital care was largely consistent with historical levels. This was followed by sharp drops in all outcomes until UK lockdown, where activity began to steadily increase. This time-period saw an average reduction of -40.7% (95% CI: -47.7 to -33.7) in A&E attendances, -25.8% (95% CI: -31.1 to -20.4) in emergency hospital admissions and -60.9% (95% CI: -66.1 to -55.7) in planned hospital admissions, in comparison to the 2018-2019 averages. All subgroup trends were broadly consistent within outcomes, but with notable variations across age groups, specialties and geography. Conclusions: COVID-19 has had a profoundly disruptive impact on hospital-based care across NHS Scotland. This has likely led to an adverse effect on non-COVID-19 related illnesses, increasing the possibility of potentially avoidable morbidity and mortality. Further research is required to elucidate these impacts.PostprintPeer reviewe

TOI-1670 c, a 40-day Orbital Period Warm Jupiter in a Compact System, is Well-aligned

We report the measurement of the sky-projected obliquity angle $\lambda$ of the Warm Jovian exoplanet TOI-1670 c via the Rossiter-McLaughlin effect as part of the Stellar Obliquities in Long-period Exoplanet Systems (SOLES) project. We observed the transit window during UT 20 April 2023 for 7 continuous hours with NEID on the 3.5 m WIYN Telescope at Kitt Peak National Observatory. TOI-1670 hosts a sub-Neptune (P ~11 days; planet b) interior to the Warm Jovian (P ~40 days; planet c), which presents an opportunity to investigate the dynamics of a Warm Jupiter with an inner companion. Additionally, TOI-1670 c is now among the longest-period planets to date to have its sky-projected obliquity angle measured. We find planet c is well-aligned to the host star, with $\lambda$ = -0.3 +/- 2.2 degrees. TOI-1670 c joins a growing census of aligned Warm Jupiters around single stars and aligned planets in multi-planet systems.Comment: 11 pages, 2 figures, 1 table. Accepted to ApJ Letter

Regulation of SNAIL1 and E-cadherin function by DNMT1 in a DNA methylation-independent context

Mammalian DNA methyltransferase 1 (DNMT1) is essential for maintaining DNA methylation patterns after cell division. Disruption of DNMT1 catalytic activity results in whole genome cytosine demethylation of CpG dinucleotides, promoting severe dysfunctions in somatic cells and during embryonic development. While these observations indicate that DNMT1-dependent DNA methylation is required for proper cell function, the possibility that DNMT1 has a role independent of its catalytic activity is a matter of controversy. Here, we provide evidence that DNMT1 can support cell functions that do not require the C-terminal catalytic domain. We report that PCNA and DMAP1 domains in the N-terminal region of DNMT1 are sufficient to modulate E-cadherin expression in the absence of noticeable changes in DNA methylation patterns in the gene promoters involved. Changes in E-cadherin expression are directly associated with regulation of β-catenin-dependent transcription. Present evidence suggests that the DNMT1 acts on E-cadherin expression through its direct interaction with the E-cadherin transcriptional repressor SNAIL1

TOI-4201: An Early M-dwarf Hosting a Massive Transiting Jupiter Stretching Theories of Core-Accretion

We confirm TOI-4201 b as a transiting Jovian mass planet orbiting an early M dwarf discovered by the Transiting Exoplanet Survey Satellite. Using ground based photometry and precise radial velocities from NEID and the Planet Finder Spectrograph, we measure a planet mass of 2.59$^{+0.07}_{-0.06}$ M$_{J}$, making this one of the most massive planets transiting an M-dwarf. The planet is $\sim$0.4\% the mass of its 0.63 M$_{\odot}$ host and may have a heavy element mass comparable to the total dust mass contained in a typical Class II disk. TOI-4201 b stretches our understanding of core-accretion during the protoplanetary phase, and the disk mass budget, necessitating giant planet formation to either take place much earlier in the disk lifetime, or perhaps through alternative mechanisms like gravitational instability.Comment: To be submitted to AAS journals on 14th July 202

Variation of morphological descriptors for the evaluation of tomato germplasm and their stability across different growing conditions

[EN] Germplasm and breeding materials are usually characterized using morphological and agronomic descriptors, which should have a high heritability. Despite the widespread use of tomato (Solanum lycopersicum) standardized descriptors, little information exists on environmental effects on descriptor values and their heritability. We have evaluated 12 tomato accessions from seven cultivar groups in three different environments (open-field conventional, open-field organic, and greenhouse) and characterized them with 36 descriptors. A wide range of variation was found for most descriptors, demonstrating their utility for describing tomato materials and their diversity and relationships. The analysis of descriptors variation reveals that while for some descriptors with a simple genetic control the accession effect accounts for 100% of the variation, for others like yield per plant only 10.83% of the variation observed is due to the accession effect. Although significant differences were found among environments for most descriptors, including a much higher yield in the open-field conventional environment than in the two others, the environmental effect was low for most traits. However, the genotype×environment effect generally had an important contribution to the structure of variation for many descriptors, and for three traits it had the highest contribution to the percentage of the sum of squares. As a result of the variation structure, the heritability values are high (> 0.7) for only 10 descriptors, while for five is low (< 0.3). Principal components analysis (PCA) reveals that projections in the PCA graph of a same accession grown in different environments plot together in the same area of the PCA graph. Although cultivar groups are generally clearly separated in the PCA graph, accessions from the same cultivar group in some cases are intermixed. These results have important implications for detecting tomato duplicates and establishing core collections, as well as for analyzing germplasm and breeding results, when using data sets containing data of accessions grown in different environments.This work has been partially funded by the TRADITOM (Traditional tomato varieties and cultural practices: a case for agricultural diversification with impacto n food security and health of European population) and G2P-SOL (Linking genetic resources, genomes and phenotypes of Solanaceous crops) projects. These projects have received funding from the European Union's Horizon 2020 research and innovation programme under grant agreements No 634561 (TRADITOM) and No 677379 (G2P-SOL). Authors are grateful to Mr. Jonatan Cerdan for his technical help.Figás-Moreno, MDR.; Prohens Tomás, J.; Casanova-Calancha, C.; Fernández De Córdova Martínez, PJ.; Soler Aleixandre, S. (2018). Variation of morphological descriptors for the evaluation of tomato germplasm and their stability across different growing conditions. Scientia Horticulturae. 238:107-115. https://doi.org/10.1016/j.scienta.2018.04.039S10711523

Modeling offenses among motorcyclists involved in crashes in Spain

In relative terms, Spanish motorcyclists are more likely to be involved in crashes than other drivers and this tendency is constantly increasing. The objective of this study is to identify the factors that are related to being an offender in motorcycle accidents. A binary logit model is used to differentiate between offender and non-offender motorcyclists. A motorcyclist was considered to be offender when she had committed at least one traffic offense at the moment previous to the crash. The analysis is based on the official accident database of the Spanish general directorate of traffic (DGT) for the 2003-2008 time period. A number of explanatory variables including motorcyclist characteristics and environmental factors have been evaluated. The results suggest that inexperienced, older females, not using helmets, absent-minded and non-fatigued riders are more likely to be offenders. Moreover, riding during the night, on weekends, for leisure purposes and along roads in perfect condition, mainly on curves, predict offenses among motorcyclists. The findings of this study are expected to be useful in developing traffic policy decisions in order to improve motorcyclist safety

The unusual M-dwarf Warm Jupiter TOI-1899~b: Refinement of orbital and planetary parameters

TOI-1899~b is a rare exoplanet, a temperate Warm Jupiter orbiting an M-dwarf, first discovered by \citet{Canas2020_toi1899} from a TESS single-transit event. Using new radial velocities (RVs) from the precision RV spectrographs HPF and NEID, along with additional TESS photometry and ground-based transit follow-up, we are able to derive a much more precise orbital period of $P = 29.090312_{-0.000035}^{+0.000036}$~d, along with a radius of $R_p = 0.99\pm0.03$~\unit{R_{J}}. We have also improved the constraints on planet mass, $M_p = 0.67\pm{0.04}$~\unit{M_{J}}, and eccentricity, which is consistent with a circular orbit at 2$\sigma$ ($e = 0.044_{-0.027}^{+0.029}$). TOI-1899~b occupies a unique region of parameter space as the coolest known ($T_{eq} \approx$ 380~K) Jovian-sized transiting planet around an M-dwarf; we show that it has great potential to provide clues regarding the formation and migration mechanisms of these rare gas giants through transmission spectroscopy with JWST as well as studies of tidal evolution.Comment: 19 pages, 7 figures, 3 tables, submitted to AJ (comments welcome

Evaluation of storm impact on sandy beaches of the Gulf of Valencia using Landsat imagery series

Supplementary data associated with this article can be found in the online version, at http://dx.doi.org/10.1016/j.geomorph.2014.02.020. These data include Google maps of the most important areas described in this article.The impact of storms on sandy beaches and the subsequent recovery process is described from an analysis of the shoreline positions obtained from Landsat 5 TM and Landsat 7 ETM + imagery. Shoreline extraction is based on an algorithm previously proposed by the authors that enables a positioning accuracy of 5 m root mean square error (RMSE). The impact of six storms registered over a period of seven months (between November 2001 and May 2002) and the beach recovery processes until December 2002 across a 100 km segment of the Gulf of Valencia on the Spanish Mediterranean coast were analysed by comparing 12 shoreline positions. The multiple shoreline positions obtained from Landsat images provide very useful information for describing the impact of storms and the recovery process across large segments of microtidal coast. This enables the identification of differences not only in the magnitude of change produced by a particular event but also in the cumulative effect associated with several storm events, and in the study of how the beach recovery process takes place. The results show a high level of spatial variability. Beaches with steep slopes experienced fewer changes than shallow slopes. The existence of well developed foredunes in some areas minimised the reduction in the beach width after the storms. Coastal orientation was another important factor in explaining storm impact and the recovery process. This factor affects not only the way the waves interact with the beaches but also the sediment longshore transport: beach regeneration is slower when the transport of sediments is limited by artificial infrastructures (groins, jetties, ports) or natural sediment traps (headlands). The main limitations of using the proposed methodology to obtain the shoreline position from Landsat images are related to: (i) the precision in the shoreline detection; (ii) the nature of the indicator obtained, that is, the water/land interface; and (iii) the registration instant defined by the image acquisition time. However, the high frequency of the data acquisition and the possibility to cover large coastal areas bring a new perspective that enriches other methods and tools used by coastal scientists.The authors appreciate the financial support provided by the Spanish Ministerio de Ciencia e Innovacion in the framework of the Projects CGL2009-14220-C02-01 and CGL2010-19591. We also thank the Direccion General de Costas in Valencia for making available the data for the tests and analysis. Finally, we would like to thank the useful suggestions provided by the anonymous referees and the assigned editor, which enabled us to improve the quality of this paper.Pardo Pascual, JE.; Almonacid Caballer, J.; Ruiz Fernández, LÁ.; Palomar-Vázquez, J.; Rodrigo-Alemany, R. (2014). Evaluation of storm impact on sandy beaches of the Gulf of Valencia using Landsat imagery series. Geomorphology. 214:388-401. doi:10.1016/j.geomorph.2014.02.020S38840121