Observational studies have reported associations between body mass index (BMI) and asthma, but confounding and reverse causality remain plausible explanations. We aim to investigate evidence for a ...causal effect of BMI on asthma using a Mendelian randomization approach.
We used Mendelian randomization to investigate causal effects of BMI, fat mass, and lean mass on current asthma at age 7½ y in the Avon Longitudinal Study of Parents and Children (ALSPAC). A weighted allele score based on 32 independent BMI-related single nucleotide polymorphisms (SNPs) was derived from external data, and associations with BMI, fat mass, lean mass, and asthma were estimated. We derived instrumental variable (IV) estimates of causal risk ratios (RRs). 4,835 children had available data on BMI-associated SNPs, asthma, and BMI. The weighted allele score was strongly associated with BMI, fat mass, and lean mass (all p-values<0.001) and with childhood asthma (RR 2.56, 95% CI 1.38-4.76 per unit score, p = 0.003). The estimated causal RR for the effect of BMI on asthma was 1.55 (95% CI 1.16-2.07) per kg/m2, p = 0.003. This effect appeared stronger for non-atopic (1.90, 95% CI 1.19-3.03) than for atopic asthma (1.37, 95% CI 0.89-2.11) though there was little evidence of heterogeneity (p = 0.31). The estimated causal RRs for the effects of fat mass and lean mass on asthma were 1.41 (95% CI 1.11-1.79) per 0.5 kg and 2.25 (95% CI 1.23-4.11) per kg, respectively. The possibility of genetic pleiotropy could not be discounted completely; however, additional IV analyses using FTO variant rs1558902 and the other BMI-related SNPs separately provided similar causal effects with wider confidence intervals. Loss of follow-up was unlikely to bias the estimated effects.
Higher BMI increases the risk of asthma in mid-childhood. Higher BMI may have contributed to the increase in asthma risk toward the end of the 20th century. Please see later in the article for the Editors' Summary.
ABSTRACT
Tuberculosis (TB) is a serious disease around the world. Bacillus Calmette–Guérin (BCG) is the only TB vaccine licensed for use in human beings, and is effective in protecting infants and ...children against severe miliary and meningeal TB. However, BCG's protective efficacy is variable in adults. Novel TB vaccine candidates being developed include whole‐cell vaccines (recombinant BCG (rBCG), attenuated Mycobacterium tuberculosis, killed M. tuberculosis or Mycobacterium vaccae), adjuvanted protein subunit vaccines, viral vector‐delivered subunit vaccines, plasmid DNA vaccines, RNA‐based vaccines etc. At least 12 novel TB vaccine candidates are now in clinical trials, including killed M. vaccae, rBCG ΔureC::hly, adjuvanted fusion proteins M72 and H56 and viral vectored MVA85A. Unfortunately, in TB, there are no correlates of vaccine‐induced protection, although cell‐mediated immune responses such as interferon‐gamma (IFN‐γ) production are widely used to assess vaccine's immunogenicity. Recent studies suggested that central memory T cells and local secreted IgA correlated with protection against TB disease. Clinical TB vaccine efficacy trials should invest in identifying correlates of protection, and evaluate new TB biomarkers emerging from human and animal studies. Accumulating new knowledge on M. tuberculosis antigens and immune profiles correlating with protection or disease risk will be of great help in designing next generation of TB vaccines.
Logging and habitat conversion create hotter microclimates in tropical forest landscapes, representing a powerful form of localised anthropogenic climate change. It is widely believed that these ...emergent conditions are responsible for driving changes in communities of organisms found in modified tropical forests, although the empirical evidence base for this is lacking.
Here we investigated how interactions between the physiological traits of genera and the environmental temperatures they experience lead to functional and compositional changes in communities of ants, a key organism in tropical forest ecosystems.
We found that the abundance and activity of ant genera along a gradient of forest disturbance in Sabah, Malaysian Borneo, was defined by an interaction between their thermal tolerance (CTmax) and environmental temperature. In more disturbed, warmer habitats, genera with high CTmax had increased relative abundance and functional activity, and those with low CTmax had decreased relative abundance and functional activity.
This interaction determined abundance changes between primary and logged forest that differed in daily maximum temperature by a modest 1.1°C, and strengthened as the change in microclimate increased with disturbance. Between habitats that differed by 5.6°C (primary forest to oil palm) and 4.5°C (logged forest to oil palm), a 1°C difference in CTmax among genera led to a 23% and 16% change in relative abundance, and a 22% and 17% difference in functional activity. CTmax was negatively correlated with body size and trophic position, with ants becoming significantly smaller and less predatory as microclimate temperatures increased.
Our results provide evidence to support the widely held, but never directly tested, assumption that physiological tolerances underpin the influence of disturbance‐induced microclimate change on the abundance and function of invertebrates in tropical landscapes.
A free Plain Language Summary can be found within the Supporting Information of this article.
A free Plain Language Summary can be found within the Supporting Information of this article.
Background Interest in the association of vascular disease with COPD and pneumonia has increased, but there is a lack of research in this area with patients with bronchiectasis. Methods A ...retrospective study of 400 patients attending a specialist bronchiectasis clinic in NHS Lothian (Edinburgh, UK) between May 2013 and September 2014 was conducted. The study assessed the prevalence of vascular disease (ischemic heart disease, cerebrovascular disease, peripheral vascular disease, and atrial fibrillation). Using multivariable models, independent risk factors were identified for vascular disease that developed following the diagnosis of bronchiectasis. Results The study included 400 patients. There was preexisting vascular disease (ie, before the diagnosis of bronchiectasis) in 44 patients (11%), and vascular disease occurred after the diagnosis of bronchiectasis after a mean of 9.4 years (95% CI, 6.0-12.8 years) in 45 patients (11%). Independent factors associated with all-cause vascular disease after the diagnosis of bronchiectasis included male sex, hypertension, receiving long-term statin therapy, and having moderate-severity bronchiectasis or worse. Conclusions In conclusion, bronchiectasis severity is independently associated with the development of vascular disease after the diagnosis of bronchiectasis. Future studies addressing the impact of primary and secondary prevention are warranted.
The Metaverse has the potential to form the next pervasive computing archetype that can transform many aspects of work and life at a societal level. Despite the many forecasted benefits from the ...metaverse, its negative outcomes have remained relatively unexplored with the majority of views grounded on logical thoughts derived from prior data points linked with similar technologies, somewhat lacking academic and expert perspective. This study responds to the dark side perspectives through informed and multifaceted narratives provided by invited leading academics and experts from diverse disciplinary backgrounds. The metaverse dark side perspectives covered include: technological and consumer vulnerability, privacy, and diminished reality, human–computer interface, identity theft, invasive advertising, misinformation, propaganda, phishing, financial crimes, terrorist activities, abuse, pornography, social inclusion, mental health, sexual harassment and metaverse-triggered unintended consequences. The paper concludes with a synthesis of common themes, formulating propositions, and presenting implications for practice and policy.
To estimate waning of covid-19 vaccine effectiveness over six months after second dose.
Cohort study, approved by NHS England.
Linked primary care, hospital, and covid-19 records within the ...OpenSAFELY-TPP database.
Adults without previous SARS-CoV-2 infection were eligible, excluding care home residents and healthcare professionals.
People who had received two doses of BNT162b2 or ChAdOx1 (administered during the national vaccine rollout) were compared with unvaccinated people during six consecutive comparison periods, each of four weeks.
Adjusted hazard ratios for covid-19 related hospital admission, covid-19 related death, positive SARS-CoV-2 test, and non-covid-19 related death comparing vaccinated with unvaccinated people. Waning vaccine effectiveness was quantified as ratios of adjusted hazard ratios per four week period, separately for subgroups aged ≥65 years, 18-64 years and clinically vulnerable, 40-64 years, and 18-39 years.
1 951 866 and 3 219 349 eligible adults received two doses of BNT162b2 and ChAdOx1, respectively, and 2 422 980 remained unvaccinated. Waning of vaccine effectiveness was estimated to be similar across outcomes and vaccine brands. In the ≥65 years subgroup, ratios of adjusted hazard ratios for covid-19 related hospital admission, covid-19 related death, and positive SARS-CoV-2 test ranged from 1.19 (95% confidence interval 1.14 to 1.24)to 1.34 (1.09 to 1.64) per four weeks. Despite waning vaccine effectiveness, rates of covid-19 related hospital admission and death were substantially lower among vaccinated than unvaccinated adults up to 26 weeks after the second dose, with estimated vaccine effectiveness ≥80% for BNT162b2, and ≥75% for ChAdOx1. By weeks 23-26, rates of positive SARS-CoV-2 test in vaccinated people were similar to or higher than in unvaccinated people (adjusted hazard ratios up to 1.72 (1.11 to 2.68) for BNT162b2 and 1.86 (1.79 to 1.93) for ChAdOx1).
The rate at which estimated vaccine effectiveness waned was consistent for covid-19 related hospital admission, covid-19 related death, and positive SARS-CoV-2 test and was similar across subgroups defined by age and clinical vulnerability. If sustained to outcomes of infection with the omicron variant and to booster vaccination, these findings will facilitate scheduling of booster vaccination.
Oxidative stress appears to initiate organ failure in sepsis, justifying treatment with antioxidants such as vitamin C at megadoses. We have therefore investigated the safety and efficacy of megadose ...sodium ascorbate in sepsis.
Interventional study.
Research Institute.
Adult Merino ewes.
Sheep were instrumented with pulmonary and renal artery flow-probes, and laser-Doppler and oxygen-sensing probes in the kidney. Conscious sheep received an infusion of live Escherichia coli for 31 hours. At 23.5 hours of sepsis, sheep received fluid resuscitation (30 mL/kg, Hartmann solution) and were randomized to IV sodium ascorbate (0.5 g/kg over 0.5 hr + 0.5 g/kg/hr for 6.5 hr; n = 5) or vehicle (n = 5). Norepinephrine was titrated to restore mean arterial pressure to baseline values (~80 mm Hg).
Sepsis-induced fever (41.4 ± 0.2°C; mean ± se), tachycardia (141 ± 2 beats/min), and a marked deterioration in clinical condition in all cases. Mean arterial pressure (86 ± 1 to 67 ± 2 mm Hg), arterial Po2 (102.1 ± 3.3 to 80.5 ± 3.4 mm Hg), and renal medullary tissue Po2 (41 ± 5 to 24 ± 2 mm Hg) decreased, and plasma creatinine doubled (71 ± 2 to 144 ± 15 µmol/L) (all p < 0.01). Direct observation indicated that in all animals, sodium ascorbate dramatically improved the clinical state, from malaise and lethargy to a responsive, alert state within 3 hours. Body temperature (39.3 ± 0.3°C), heart rate (99.7 ± 3 beats/min), and plasma creatinine (32.6 ± 5.8 µmol/L) all decreased. Arterial (96.5 ± 2.5 mm Hg) and renal medullary Po2 (48 ± 5 mm Hg) increased. The norepinephrine dose was decreased, to zero in four of five sheep, whereas mean arterial pressure increased (to 83 ± 2 mm Hg). We confirmed these physiologic findings in a coronavirus disease 2019 patient with shock by compassionate use of 60 g of sodium ascorbate over 7 hours.
IV megadose sodium ascorbate reversed the pathophysiological and behavioral responses to Gram-negative sepsis without adverse side effects. Clinical studies are required to determine if such a dose has similar benefits in septic patients.
A response to Murshed et al., J Nanopart Res (2010) 12:2007–2010 Evans, Tom M.; Doroodchi, Elham; Moghtaderi, Behdad
Journal of nanoparticle research : an interdisciplinary forum for nanoscale science and technology,
09/2011, Letnik:
13, Številka:
9
Journal Article
This brief communication provides a response to Murshed et al. (J Nanopart Res 12:2007–2010,
2010
). We acknowledge that three of the equations in our original article (Doroodchi et al. J Nanopart ...Res 11:1501–1507,
2009
) contained minor typographical errors. However, we confirm that these misprinted equations have no bearing on the results presented within that article. In addition, we would like to clarify that we do not challenge the methodology of Leong et al. (J Nanopart Res 8:245–254,
2006
). Instead, we repeated their analysis using a more general form for the temperature field with continuity imposed across the particle–nanolayer–liquid interfaces and found that the solution reduces to the Renovated-Maxwell model.
Astrophysical false positives due to stellar eclipsing binaries pose one of the greatest challenges to ground-based surveys for transiting hot Jupiters. We have used known properties of multiple star ...systems and hot Jupiter systems to predict, a priori, the number of such false detections and the number of genuine planet detections recovered in two hypothetical but realistic ground-based transit surveys targeting fields close to the galactic plane (b {approx} 10{sup 0}): a shallow survey covering a magnitude range 10 < V < 13 and a deep survey covering a magnitude range 15 < V < 19. Our results are consistent with the commonly reported experience of false detections outnumbering planet detections by a factor of {approx}10 in shallow surveys, while in our synthetic deep survey we find {approx}1-2 false detections for every planet detection. We characterize the eclipsing binary configurations that are most likely to cause false detections and find that they can be divided into three main types: (1) two dwarfs undergoing grazing transits, (2) two dwarfs undergoing low-latitude transits in which one component has a substantially smaller radius than the other, and (3) two eclipsing dwarfs blended with one or more physically unassociated foreground stars. We also predict that a significant fraction of hot Jupiter detections are blended with the light from other stars, showing that care must be taken to identify the presence of any unresolved neighbors in order to obtain accurate estimates of planetary radii. This issue is likely to extend to terrestrial planet candidates in the CoRoT and Kepler transit surveys, for which neighbors of much fainter relative brightness will be important.
Itaconic acid is an important metabolite produced by macrophages after stimulation with LPS. The role of itaconate in the inflammatory cascade is unclear. Here we used 13Citaconate and dimethyl ...13Citaconate (DMI) to probe itaconate metabolism, and find that 13CDMI is not metabolized to itaconate. 13CItaconate in the cell culture medium leads to elevated intracellular levels of unlabeled succinate, with no evidence of intracellular uptake. The goal of this study is to encourage the development of effective pro-drug strategies to increase the intracellular levels of itaconate, which will enable more conclusive analysis of its action on macrophages and other cell and tissue types.
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