Evidence For Deviations Research Articles

Portfolio Diet Score and Risk of Cardiovascular Disease: Findings From 3 Prospective Cohort Studies.

The plant-based Portfolio dietary pattern includes recognized cholesterol-lowering foods (ie, plant protein, nuts, viscous fiber, phytosterols, and plant monounsaturated fats) shown to improve several cardiovascular disease (CVD) risk factors in randomized controlled trials. However, there is limited evidence on the role of long-term adherence to the diet and CVD risk. The primary objective was to examine the relationship between the Portfolio Diet Score (PDS) and the risk of total CVD, coronary heart disease (CHD), and stroke. We prospectively followed 73 924 women in the Nurses' Health Study (1984-2016), 92 346 women in the Nurses' Health Study II (1991-2017), and 43 970 men in the Health Professionals Follow-up Study (1986-2016) without CVD or cancer at baseline. Diet was assessed using validated food frequency questionnaires at baseline and every 4 years using a PDS that positively ranks plant protein (legumes), nuts and seeds, viscous fiber sources, phytosterols (mg/day), and plant monounsaturated fat sources, and negatively ranks foods high in saturated fat and cholesterol. During up to 30 years of follow-up, 16 917 incident CVD cases, including 10 666 CHD cases and 6473 strokes, were documented. After multivariable adjustment for lifestyle factors and a modified Alternate Healthy Eating Index (excluding overlapping components), comparing the highest with the lowest quintile, participants with a higher PDS had a lower risk of total CVD (pooled hazard ratio [HR], 0.86 [95% CI, 0.81-0.92]; Ptrend<0.001), CHD (pooled HR, 0.86 [95% CI, 0.80-0.93]; Ptrend=0.0001), and stroke (pooled HR, 0.86 [95% CI, 0.78-0.95]; Ptrend=0.0003). In addition, a 25-percentile higher PDS was associated with a lower risk of total CVD (pooled HR, 0.92 [95% CI, 0.89-0.95]), CHD (pooled HR, 0.92 [95% CI, 0.88-0.95]), and stroke (pooled HR, 0.92 [95% CI, 0.87-0.96]). Results remained consistent across sensitivity and most subgroup analyses, and there was no evidence of departure from linearity for CVD, CHD, or stroke. In a subset of participants, a higher PDS was associated with a more favorable blood lipid and inflammatory profile. The PDS was associated with a lower risk of CVD, including CHD and stroke, and a more favorable blood lipid and inflammatory profile, in 3 large prospective cohorts.

Diurnal Cycling of Insulin Sensitivity in Type 2 Diabetes: Evidence for Deviation From Physiology at an Early Stage.

In people with type 2 diabetes (T2D), fasting hyperglycemia is greater in the morning (a.m.) versus the afternoon (p.m.), and insulin sensitivity for glucose and lipid metabolism is lower a.m. versus p.m. This pattern is the reverse of the physiological diurnal cycle of people without diabetes who are more insulin sensitive a.m. versus p.m. These new findings have been observed in the present study in people without obesity but with recent-onset T2D, with good glycemic control, and in the absence of confounding pharmacological treatment. It is likely that the findings represent a specific marker of T2D, possibly present even in prediabetes before biochemical and clinical manifestations.

Individualized patient care in nodular lymphocyte-predominant Hodgkin lymphoma

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma that has traditionally been considered a subgroup of Hodgkin lymphoma. However, morphology, surface marker expression, genetics, and clinical course are different from classic Hodgkin lymphoma. While most patients experience indolent disease with slow progression, some patients can also have more aggressive disease. Nevertheless, outcomes are excellent, and excess mortality due to NLPHL is at most very low. The treatment of newly diagnosed NLPHL has historically mirrored that of classic Hodgkin lymphoma. However, evidence for deviations from that approach has emerged over time and is discussed herein. Less evidence is available for the optimal management of relapsed patients. So-called variant histology has recently emerged as a biological risk factor, providing at least a partial explanation for the observed heterogeneity of NLPHL. Considering variant histology together with other risk factors and careful observation of the clinical course of the disease in each patient can help to assess individual disease aggressiveness. Also important in this mostly indolent disease are the preferences of the patient and host factors, such as individual susceptibility to specific treatment side effects. Considering all this together can guide individualized treatment recommendations, which are paramount in this rare disease.

Pooled Analysis of Meningioma Risk Following Treatment for Childhood Cancer

Meningioma is the most common subsequent neoplasm following cranial irradiation among survivors of childhood cancer, but there are still uncertainties regarding the magnitude of the radiation dose-response association, potential modifiers of radiation risks, and the role of chemotherapy. To evaluate meningioma risk in survivors of childhood cancer following radiotherapy and chemotherapy and identify possible modifying factors of radiation-associated risk. This international case-control study pooled data from 4 nested case-control studies of survivors of childhood cancer diagnosed between 1942 and 2000, followed through 2016. Cases were defined as participants diagnosed with a subsequent meningioma. Controls were matched to cases based on sex, age at first cancer diagnosis, and duration of follow-up. Data were analyzed from July 2019 to June 2022. Radiation dose (Gy) to the meningioma site and cumulative chemotherapy doses, including intrathecal and systemic methotrexate doses. The main outcome was subsequent meningioma, assessed using odds ratios (ORs) and excess odds ratios per gray (EOR/Gy). The analysis included 273 survivors of childhood cancer who developed meningioma (cases) and 738 survivors who did not (controls), with a total of 1011 individuals (median [IQR] age at first cancer diagnosis 5.0 [3.0-9.2] years; 599 [59.2%] female). Median (IQR) time since first cancer was 21.5 (15.0-27.0) years. Increasing radiation dose was associated with increased risk of meningioma (EOR/Gy, 1.44; 95% CI, 0.62-3.61), and there was no evidence of departure from linearity (P = .90). Compared with survivors who were not exposed to radiation therapy, those who received doses of 24 Gy or more had more than 30-fold higher odds of meningioma (OR, 33.66; 95% CI, 14.10-80.31). The radiation dose-response association was significantly lower among patients treated at age 10 years or older compared with those treated before age 10 years (EOR/Gy, 0.57; 95% CI, 0.18-1.91 vs 2.20; 95% CI, 0.87-6.31; P for heterogeneity = .03). Risk associated with radiation remained significantly elevated 30 years after exposure (EOR/Gy, 3.76; 95% CI, 0.77-29.15). We found an increased risk of meningioma among children who had received methotrexate (OR, 3.43; 95% CI, 1.56-7.57), but no evidence of a dose-response association or interaction with radiation dose. These findings suggest that the meninges are highly radiosensitive, especially for children treated before age 10 years. These results support the reduction in whole-brain irradiation over recent decades and the prioritization of approaches that limit radiation exposure in healthy tissue for children. The persistence of elevated risks of meningiomas for 30 years after cranial radiotherapy could help inform surveillance guidelines.

An asymmetric electron-scattering photosphere around optical tidal disruption events

A star crossing the tidal radius of a supermassive black hole will be spectacularly ripped apart with an accompanying burst of radiation. A few tens of such tidal disruption events have now been identified in optical wavelengths, but the exact origin of the strong optical emission remains inconclusive. Here we report polarimetric observations of three tidal disruption events. The continuum polarization appears independent of wavelength, while emission lines are partially depolarized. These signatures are consistent with photons being scattered and polarized in an envelope of free electrons. An almost axisymmetric photosphere viewed from different angles is in broad agreement with the data, but there is also evidence for deviations from axial symmetry before the peak of the flare and significant time evolution at early times, compatible with the rapid formation of an accretion disk. By combining a super-Eddington accretion model with a radiative transfer code, we simulate the polarization degree as a function of disk mass and viewing angle and we show that the predicted levels are compatible with the observations for extended reprocessing envelopes of ~1,000 gravitational radii. Spectropolarimetry therefore constitutes a new observational test for tidal disruption event models, and opens an important new line of exploration in the study of tidal disruption events. Spectropolarimetric observations of three tidal disruption events reveal that they are optically polarized at the 1–2% level by a cloud of electrons surrounding the black hole (in good agreement with theory).

Accuracy order in L2 grammatical morphemes: Corpus evidence from different proficiency levels of Turkish learners of English

The present study empirically scrutinizes the fixed natural order of grammatical morphemes relying on a manual analysis of an EFL learner corpus. Specifically, we test whether the accuracy order of L2 grammatical morphemes in the case of L1 Turkish speakers of English deviates from Krashen’s (1977) natural order and whether proficiency levels play a role in the order of acquisition of these morphemes. With this in mind, we focus on the (in)accuracy of nine English grammatical morphemes with 2883 cases manually tagged by the UAM Corpus Tool in the written exam scripts of Turkish learners of English. The results based on target-like use scores provide evidence for deviation from what is widely believed to be a set order of acquisition of these grammatical morphemes by second language learners. In light of such findings, we challenge the view that the internally driven processes of mastering grammatical morphemes in English for interlanguage users are largely independent of their L1. Regardless of L2 grammar proficiency in our data, the observed accuracy of some morphemes ranked low in comparison with the so-called natural order. These grammatical morphemes were almost exclusively non-existent features in participants’ mother tongue (e.g., third person singular –s, articles and the irregular past tense forms), thus suggesting the influence of L1 in this respect.

Description of the growth hormone gene of the Australasian snapper, Chrysophrys auratus, and associated intra- and interspecific genetic variation.

The growth hormone (GH) gene of the marine teleost, the Australasian snapper (Chrysophrys auratus), was identified and characterized from the reference genome showing it was approximately 5577 bp in length and consisted of six exons and five introns. Large polymorphic repeat regions were found in the first and third introns, and putative transcription factor binding sites were identified. Phylogenetic analysis of the GH genes of perciform fish showed largely conserved coding regions and highly variable noncoding regions among species. Despite some exon sequence variation and an amino acid deletion identified between C. auratus and its sister species Chrysophrys/Pagrus major, the amino acid sequences and putative secondary structures were largely conserved across the Sparidae. A population-level assessment of 99 samples caught at five separate coastal locations in New Zealand revealed six variable alleles at the intron 1 site of the C. auratus GH gene. A population genetic analysis suggested that C. auratus from the five sample locations were largely panmictic, with no evidence for departure from the Hardy-Weinberg equilibrium, and have a high level of heterozygosity. Overall these results suggest that the GH gene is largely conserved across the coding regions, but some variability could be detected.

Ethnic Differences in the Association Between Body Mass Index and Type 2 Diabetes Risk: A Meta-Analysis of Prospective Cohort Studies

ObjectivesThe association between body mass index (BMI) and total body adiposity differs across ethnic groups. For instance, South Asians (SA) and East Asians (EA) have lower body fat for a given BMI level than Europeans, while the opposite is true for African-Caribbeans (AC). This suggests that the relationship between BMI and type 2 diabetes (T2D) risk may also vary depending on ethnicity. We conducted a meta-analysis to investigate whether the association between BMI and the risk of T2D differs across ethnic groups. MethodsMEDLINE, EMBASE and Web of Science were searched up to July 2020. We included prospective cohort studies of >2 years, which investigated the association between BMI and T2D incidence among adults of a specified ethnicity. Linear and non-linear dose-response meta-analyses were performed using random effects models, with subgroup analyses by ethnicity. The heterogeneity among studies was estimated using the Cochran Q test and I2 statistic. Study quality was assessed with the Newcastle-Ottawa Scale. Results54 studies were included. Cohorts were stratified into the following ethnic subgroups: AC (N = 67,453), EA (N = 1,012,135), European (N = 206,424), Indigenous (N = 10,533), Latin American (LA) (N = 4,669), SA (N = 9,395), and Southeast Asian (SEA) (N = 51,129). Linear dose-response associations between 1 kg/m2 increase in BMI and T2D were observed for the SEA (RR = 1.26; 95% CI, 1.10, 1.30) and SA (RR = 1.11; 95% CI: 1.04, 1.19) subgroups with no evidence of departure from linearity. Associations departed from linearity for all other subgroups. At a BMI level of 30 kg/m2, the non-linear dose-response curves for each of the other subgroups displayed the following risk ratios; AC: RR = 3.13 (95% CI, 1.95, 5.02), EA: RR = 2.39 (95% CI, 1.96, 2.92), European: RR = 7.41 (95% CI, 3.88, 14.18), Indigenous: RR = 8.15 (95% CI, 6.07; 10.95), and LA: RR = 12.82 (95% CI, 5.50, 29.92). For all subgroups, there was a high degree of interstudy heterogeneity (I2 > 75%). ConclusionsOur findings indicated that the association between BMI and the risk of T2D differs across ethnic groups, suggesting that ethnic-specific BMI cut-offs could be helpful in identifying cardiometabolic risk profiles across different populations. Funding SourcesCanadian Institutes for Health Research.

“The Meranaw Rina-rinaw and its Emerging Semiotic Resources”

This study aims to discover the emerging semiotic resources found in the Meranaw rina-rinaw. Through semiotic analysis, this ethnographic research determines how faithful the rina-rinaw has remained to the prototype, the traditional bayok, or how far it has drifted from the latter. Specifically, this study seeks to identify and discuss how the semiotic resources contribute to the meaning-making function of the rina-rinaw. The findings revealed the emerging semiotic resources such as the use of guitar as a musical accompaniment, the wearing of modern evening gowns instead of the Meranaw traditional malong or landap, transfer of the setting from the torogan to a private residence or more public place, and less formality and exclusiveness of the contemporary rina-rinaw event which, unlike the traditional bayok, is performed for the delectation of the general public. These semiotic resources have evolved in its own time. There are also evidence of departures or breaks where singers no longer exhibit the typical Meranaw arts of “kakini-kini” and “kakurum.” Instead, the onor walks naturally toward the stage. Moreover, the rina-rinaw event is open for everyone. The audience is no longer as exclusive as that of the traditional bayok; it is more heterogeneous. The participants could become rowdy or boisterous.

The association between Sugars Sweetened Beverages (SSBs) and lipid profile among children and youth: A systematic review and dose-response meta-analysis of cross-sectional studies.

The relationship between sugar-sweetened beverages (SSBs) intake and serum lipids among children and youth has been reported in several studies, but the results are still controversial. In the current study, we summarized the results of studies that assessed the relationship between SSBs consumption and serum lipids among children and youth in a systematic review and dose-response meta-analysis. The PubMed, Web of Sciences, Cochrane and Scopus electronic databases were searched for observational studies reporting an association between SSBs intake and serum lipids among children and youth that were published before May 2020. For data extracted from cohort studies, only cross-sectional baseline data were included in the current meta-analysis. The Random effects model was used to estimate the pooled weighted mean difference (WMD) and 95% confidence intervals (CI). Heterogeneity was assessed with the Cochran Q test and I2 statistics. In our search, 1845 studies were retrieved of which 13 studies (two cohorts and eleven cross-sectional) were included. High SSB consumption was associated with 1.21 mg/dL increase in low-density lipoprotein cholesterol (LDL-C; pooled WMD: 1.21 mg/dL; 95% CI: 0.23, 2.20; P= .01), 1.45 mg/dL decrease in high-density lipoprotein cholesterol (HDL-C, pooled WMD: -1.46 mg/dL; 95% CI, -2.25, -0.67; P< .0001) and 2.49 mg/dL decrease in total cholesterol (TC, pooled WMD: -2.49 mg/dL; 95% CI, -2.89, -2.10; P< .0001). In dose-response meta-analysis, there was an evidence of departure from linearity in the relationship between SSB consumption and change in LDL-C (P-nonlinearity = .03) and TC (P-nonlinearity = .01). However, no departure from linearity was observed between SSB intake and change in HDL-C (P-nonlinearity = .56) or triglyceride (TG) values (P-nonlinearity = .85). According to our results, high SSB consumption was significantly associated with higher LDL-C and lower HDL-C and TC among children and youth. However, owing to the limited number of the included studies, further well-designed interventional studies are needed to better elucidate causality.

Rastall gravity extension of the standard Lambda CDM model: theoretical features and observational constraints

We present a detailed investigation of the Rastall gravity extension of the standard Lambda CDM model. We review the model for two simultaneous modifications of different nature in the Friedmann equation due to the Rastall gravity: the new contributions of the material (actual) sources (considered as effective source) and the altered evolution of the material sources. We discuss the role/behavior of these modifications with regard to some low redshift tensions, including the so-called H_0 tension, prevailing within the standard Lambda CDM. We constrain the model at the level of linear perturbations, and obtain the first constraints through a robust and accurate analysis using the latest full Planck cosmic microwave background (CMB) data, with and without including baryon acoustic oscillations (BAO) data. We find that the Rastall parameter epsilon (null for general relativity) is consistent with zero at 68% CL (with a tendency towards positive values, -0.0001< epsilon < 0.0007 (CMB+BAO) at 68% CL), which in turn implies no significant statistical evidence for deviation from general relativity, and also a precision of mathcal {O}(10^{-4}) for the coefficient -1/2 of the term g_{mu nu }R in the Einstein field equations of general relativity (guaranteeing the local energy-momentum conservation). We explore the consequences led by the Rastall gravity on the cosmological parameters in the light of the observational analyses. It turns out that the effective source, with a present-day density parameter Omega _mathrm{X0}=-0.0010pm 0.0013 (CMB+BAO, 68% CL), dynamically screens the usual vacuum energy at high redshifts, but this mechanism barely works due to the opposition by the altered evolution of cold dark matter. Consequently, two simultaneous modifications of different nature in the Friedmann equation by the Rastall gravity act against each other, and do not help to considerably relax the low redshift tensions, including the so-called H_0 tension. Our results may offer a guide for the research community that studies the Rastall gravity in various aspects of gravitation and cosmology.

Safety, pharmacodynamic, and pharmacokinetic characterization of vericiguat: results from six phase I studies in healthy subjects

PurposeTo characterize the safety, pharmacodynamics, and pharmacokinetics (PK) of vericiguat in healthy males.MethodsSix phase I studies were conducted in European, Chinese, and Japanese males. Subjects received oral vericiguat as a single dose (0.5–15.0 mg solution [for first-in-human study] or 1.25–10.0 mg immediate release [IR tablets]) or multiple doses (1.25–10.0 mg IR tablets once daily [QD] or 5.0 mg IR tablets twice daily for 7 consecutive days). Bioavailability and food effects on vericiguat PK (IR tablets) were also studied in European subjects.ResultsOverall, 255 of 265 randomized subjects completed their respective studies. There were no deaths or serious adverse events. Vericiguat was generally well tolerated at doses ≤ 10.0 mg. In the first-in-human study, the most frequent drug-related adverse events were headache and postural dizziness (experienced by five subjects each [7.2%]). Three of four subjects who received vericiguat 15.0 mg (oral solution, fasted) experienced orthostatic reactions. Vericiguat (≤ 10.0 mg, IR tablets) was rapidly absorbed (median time to reach maximum plasma concentration ≤ 2.5 h [fasted]) with a mean half-life of about 22.0 h (range 17.9–27.0 h for single and multiple doses). No evidence for deviation from dose proportionality or unexpected accumulation was observed. Administration of vericiguat 5.0 mg IR tablets with food increased bioavailability by 19% (estimated ratio 119% [90% confidence interval]: 108; 131]), reduced PK variability, and prolonged vericiguat absorption relative to the fasted state.ConclusionIn general, vericiguat was well tolerated. These results supported further clinical evaluation of vericiguat QD in patients with heart failure.Registry numbersEudraCT: 2011-001627-21; EudraCT: 2012-000953-30

An updated systematic review and dose-response meta-analysis of the effects of α-lipoic acid supplementation on glycemic markers in adults.

This systematic review and dose-response meta-analysis was conducted to summarize data from available clinical trials on the effects of α-lipoic acid (ALA) supplementation on glycemic markers including glucose, hemoglobin A1c (HbA1c), insulin, homeostatic model assessment of insulin resistance (HOMA-IR), HOMA-β, and quantitative insulin check index in adults. A comprehensive literature search was conducted in the electronic databases of PubMed, Web of Science, ProQuest, Embase and SCOPUS from inception to February 2020. Among all of the eligible studies, 28 articles were selected. The weighted mean differences (WMD) and 95% confidence intervals (CI) were calculated to evaluate the pooled effect size. Between-study heterogeneity was evaluated using Cochran's Q test and I2. Subgroup analysis was done to evaluate the potential sources of heterogeneity. The dose-response relationship was evaluated using fractional polynomial modeling. Twenty eight eligible studies with a total sample size of 1,016 participants were included in the current meta-analysis. The findings of the meta-analysis showed that ALA supplementation significantly reduced insulin (WMD: -0.64; CI: -1.287 to 0.004, P=.04), HOMA-IR (WMD: -0.48; 95% CI: -0.79 to -0.16; P=.002). No change in glucose or HbA1C was reported. Moreover, the effect of ALA on insulin was duration-dependent (Pnon-linearity=0.04). No evidence of departure from linearity was observed between dose and duration of the ALA supplementation on other markers. The subgrouping revealed that ALA dosage and duration of ALA supplementation, health status of participants, geographic locations and the studies' quality are possible sources of heterogeneity. In summary, ALA supplementation improves serum insulin and insulin resistance in a two-class and duration dependent non-linear analysis.

Alpha-lipoic acid supplementation significantly reduces the risk of obesity in an updated systematic review and dose response meta-analysis of randomised placebo-controlled clinical trials.

There are numerous trials reported the effect of alpha-lipoic acid (ALA) on obesity measurements; while no summarised dose-response meta-analysis is available to address the effects of dose and duration of ALA supplementation on obesity measurements. We aimed to summarise the results of studies evaluating the effects of ALA supplementation on obesity measurements in a systematic review and dose-response meta-analysis. In a systematic search from Scopus, PubMed, Embase, Proquest electronic databases up to January 2020 relevant studies were retrieved. Randomised, placebo-controlled trials investigating the effect of ALA supplementation on obesity measurements including weight, body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR) and fat mass (FM) were included. Two class and dose-response meta-analysis were performed to data analysis. Totally, 18, 21 and 8 studies were included for the meta-analysis of ALA-weight, ALA-BMI, ALA-WC, respectively. In the two-class meta-analysis, ALA treatment significantly reduced weight (WMD: -2.29kg, 95% CI: -2.98, 1.60, P<.01) and BMI (WMD: -0.49kg/m2 , 95% CI:-0.83,-0.15, P=.005) but no effect on WC (WMD: -2.57cm, 95% CI: -8.91, 3.76; P=.426). While the dose-response meta-analysis revealed that the duration of ALA treatment is a significant factor affecting WC reduction (Pnon-linearity =.047). While no evidence of departure from linearity was observed for other variables; moreover, subgrouping also revealed that gender could be an important factor affecting the ALA impact on WC which was significant among women (WMD: -4.099; CI: -7.837, -0.361; P=.032). According to our finding, ALA treatment significantly reduced BMI, weight in a two-class meta-analysis without evidence of departure from linearity in terms of dose or duration. While the association of ALA treatment on WC is dependent to the duration of the study. Although further trials evaluating the other obesity measurements specially central obesity will be helpful to infer a more reliable result.

Alcohol consumption in relation to carotid subclinical atherosclerosis and its progression: results from a European longitudinal multicentre study

Background/AimThe association between alcohol consumption and subclinical atherosclerosis is still unclear. Using data from a European multicentre study, we assess subclinical atherosclerosis and its 30-month progression by carotid intima-media thickness (C-IMT) measurements, and correlate this information with self-reported data on alcohol consumption.MethodsBetween 2002–2004, 1772 men and 1931 women aged 54–79 years with at least three risk factors for cardiovascular disease (CVD) were recruited in Italy, France, Netherlands, Sweden, and Finland. Self-reported alcohol consumption, assessed at baseline, was categorized as follows: none (0 g/d), very-low (0 − 5 g/d), low (> 5 to ≤ 10 g/d), moderate (> 10 to ≤ 20 g/d for women, > 10 to ≤ 30 g/d for men) and high (> 20 g/d for women, > 30 g/d for men). C-IMT was measured in millimeters at baseline and after 30 months. Measurements consisted of the mean and maximum values of the common carotids (CC), internal carotid artery (ICA), and bifurcations (Bif) and whole carotid tree. We used quantile regression to describe the associations between C-IMT measures and alcohol consumption categories, adjusting for sex, age, physical activity, education, smoking, diet, and latitude.ResultsAdjusted differences between median C-IMT values in different levels of alcohol consumption (vs. very-low) showed that moderate alcohol consumption was associated with lower C-IMTmax[− 0.17(95%CI − 0.32; − 0.02)], and Bif-IMTmean[− 0.07(95%CI − 0.13; − 0.01)] at baseline and decreasing C-IMTmean[− 0.006 (95%CI − 0.011; − 0.000)], Bif-IMTmean[− 0.016(95%CI − 0.027; − 0.005)], ICA-IMTmean[− 0.009(95% − 0.016; − 0.002)] and ICA-IMTmax[− 0.016(95%: − 0.032; − 0.000)] after 30 months. There was no evidence of departure from linearity in the association between alcohol consumption and C-IMT.ConclusionIn this European population at high risk of CVD, findings show an inverse relation between moderate alcohol consumption and carotid subclinical atherosclerosis and its 30-month progression, independently of several potential confounders.

Gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) potentially increases the risk of obesity in adults: An exploratory systematic review and dose-response meta- analysis.

It has been suggested that trimethylamine N-oxide (TMAO) is associated with increased risk of diabetes and cardiovascular disease (CVD) morbidity and mortality. However, it is not known whether increased TMAO concentrations is associated with obesity. In the current study, we summarized the evidence related to the association of circulating TMAO with the risk of obesity measurements, including body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) in a two-class and dose-response meta-analysis of observational studies. A systematic search carried out in PubMed, SCOPUS, Cochrane, and ProQuest through September 30, 2019 resulted in 12 eligible studies which were included in the current meta-synthesis. In these studies, BMI was reported but there were no reports of WC or WHR. Meta-analysis of two-class variables and dose-response meta-analysis of continuous variables were performed. Subgroup analysis and meta-regression were also performed to identify the source of heterogeneity. There was a dose-response association between circulating TMAO concentration and increased BMI in studies involving healthy individuals (P nonlinearity = .007), while no evidence of departure from linearity was observed according to study design or among patients with CVD. Results showed the highest category of TMAO was associated with 0.56 kg/m2 increase in BMI (weighted mean difference [WMD], 0.563; CI, 0.026-1.100; P = .04). The results of the current meta-analysis revealed a positive association between circulating TMAO and obesity as presented by increased BMI. Moreover, a dose-dependent association between circulating TMAO and obesity was also identified in apparently healthy individuals. This is the first meta-analysis to reveal positive dose-dependent associations between circulating TMAO concentration and obesity.

Moving from two- to multi-way interactions among binary risk factors on the additive scale

Many studies have focused on investigating deviations from additive interaction of two dichotomous risk factors on a binary outcome. There is, however, a gap in the literature with respect to interactions on the additive scale of >2 risk factors. In this paper, we present an approach for examining deviations from additive interaction among three or more binary exposures. The relative excess risk due to interaction (RERI) is used as measure of additive interaction. First, we concentrate on three risk factors – we propose to decompose the total RERI to: the RERI owned to the joint presence of all three risk factors and the RERI of any two risk factors, given that the third is absent. We then extend this approach, to >3 binary risk factors. For illustration, we use a sample from data from the Greek EPIC cohort and we investigate the association with overall mortality of Mediterranean diet, body mass index , and smoking. Our formulae enable better interpretability of any evidence for deviations from additivity owned to more than two risk factors and provide simple ways of communicating such results from a public health perspective by attributing any excess relative risk to specific combinations of these factors. Abbreviations: BMI: Body Mass Index; ERR: excess relative risk; EPIC: European Prospective Investigation into Cancer and nutrition; MD: Mediterranean diet; RERI: relative excess risk due to interaction; RR: relative risk; TotRERI: total relative excess risk due to interaction

Representing the Heat-to-Moisture Transport Efficiency in Stable Conditions: An Extension of Two Different Approaches

Using eddy-covariance turbulence measurements over a Tibetan glacier, we present a description of scalar turbulence characteristics in the stable boundary layer. Interesting behaviours are demonstrated in terms of temperature–humidity de-correlation and dissimilarity. That is, a lack of perfect correlation occurs between the two scalars (i.e., correlation coefficients <1 in magnitude); overall, sensible heat is more efficiently transported than water vapour over snow and ice surfaces. Such behaviours provide evidence of departures from the idealized expectation of Monin–Obukhov similarity theory—all scalars assume a perfect level of linear correlation and an equal efficiency level of vertical transport. Results presented herein are noteworthy in that observations over uniform glaciated surfaces involve negligible effects of either a canopy-induced roughness sublayer or heterogeneity in the temperature–humidity source/sink distributions. Moreover, we address two different approaches to representing the heat-to-moisture transport efficiency in stable conditions. A new approach is extended through application of the quadrant analysis technique, thereby representing it as a function of atmospheric stability. Caution is further advised in the use of this approach, when temperature–humidity turbulence becomes markedly de-correlated. A second approach, as previously applied for estimating forest evaporation fluxes in unstable conditions, is extended to a stable boundary layer over snow and ice surfaces.

Short-Term Exposure to Ambient Air Pollution and Asthma Mortality.

Rationale: Short-term exposure to air pollution has been associated with asthma exacerbation and increased healthcare use caused by asthma, but its effect on asthma mortality remains largely unknown. Objectives: To quantitatively assess the association between short-term exposure to air pollution and asthma mortality. Methods: We investigated 4,454 individuals who lived in Hubei province, China, and died from asthma between 2013 and 2018. A case-crossover design and conditional logistic regression models were applied for data analyses. Exposures to particulate matter ≤2.5 μm in aerodynamic diameter (PM2.5), particulate matter ≤10 μm in aerodynamic diameter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) were estimated by inverse distance weighted averages of all monitoring stations within 50 km from each case's home address. Measurements and Main Results: Each interquartile range (IQR) increase of PM2.5 (lag 3; IQR, 47.1 μg/m3), NO2 (lag 03; IQR, 26.3 μg/m3), and O3 (lag 3; IQR, 52.9 μg/m3) were positively associated with asthma mortality, with odds ratios of 1.07 (95% confidence interval, 1.01-1.12), 1.11 (95% confidence interval, 1.01-1.22), and 1.09 (95% confidence interval, 1.01-1.18), respectively. There was no evidence of departure from linearity for these associations. Further adjustment for other pollutants did not change the associations materially. We did not observe significant associations between PM10, SO2, and CO exposures and asthma mortality. Overall, the estimates remained consistent in various sensitivity analyses. Conclusions: Our results provide new evidence that short-term exposures to PM2.5, NO2, and O3 may increase asthma mortality risk. Further studies are needed to confirm our findings in other populations.

The slope of the source-count distribution for fast radio bursts

The slope of the source-count distribution of fast radio burst (FRB) fluences, $\alpha$, has been estimated using a variety of methods. Hampering all attempts have been the low number of detected FRBs, and the difficulty of defining a completeness threshold for FRB surveys. In this work, we extend maximum-likelihood methods for estimating $\alpha$, using detected and threshold signal-to-noise ratios applied to all FRBs in a sample without regard to a completeness threshold. Using this method with FRBs detected by the Parkes radio telescope, we find $\alpha=-1.18 \pm 0.24$ (68\% confidence interval, C.I.), i.e.\ consistent with a non-evolving Euclidean distribution ($\alpha=-1.5$). Applying these methods to the Australian Square Kilometre Array Pathfinder (ASKAP) Commensal Real-time ASKAP Fast Transients (CRAFT) FRB survey finds $\alpha=-2.2 \pm 0.47$ (68\% C.I.). A full maximum-likelihood estimate finds an inconsistency with the Parkes rate with a p-value of 0.86\% ($2.6\, \sigma$). If not due to statistical fluctuations or biases in Parkes data, this is the first evidence for deviations from a pure power law in the integral source-count distribution of FRBs. It is consistent with a steepening of the integral source-count distribution in the fluence range 5--40\,Jy\,ms, for instance due to a cosmological population of FRB progenitors evolving more rapidly than the star-formation rate, and peaking in the redshift range 1--3.