Socioeconomic status and neural processing of a go/no-go task in preschoolers: an assessment of the P3b

While it is well established that lower socioeconomic status (SES) is associated with poorer executive functioning (EF), how SES relates to the neural processing of EF in childhood remains largely unexplored. We examined how household income and parent education related to amplitudes of the P3b, an event-related potential component, during one EF task. We assessed the P3b, indexing inhibition and attention allocation processes, given the importance of these skills for academic success. Children aged 4.5-5.5 years completed a go/no-task, which assesses inhibitory control and attention, while recording EEG. The P3b was assessed for both go trials (indexing sustained attention) and no-go trials (indexing inhibition processes). Higher household income was related to larger P3b amplitudes on both go and no-go trials. This was a highly educated sample, thus results indicate that P3b amplitudes are sensitive to household income even within the context of high parental education. Findings build on the behavioral literature and demonstrate that SES also has implications for the neural mechanisms underlying inhibition and attention processing in early childhood.Published versio

Lateralization of ERPs to speech and handedness in the early development of Autism Spectrum Disorder

Background: Language is a highly lateralized function, with typically developing individuals showing left hemispheric specialization. Individuals with autism spectrum disorder (ASD) often show reduced or reversed hemispheric lateralization in response to language. However, it is unclear when this difference emerges and whether or not it can serve as an early ASD biomarker. Additionally, atypical language lateralization is not specific to ASD as it is also seen more frequently in individuals with mixed- and left-handedness. Here, we examined early asymmetry patterns measured through neural responses to speech sounds at 12 months and behavioral observations of handedness at 36 months in children with and without ASD. Methods: Three different groups of children participated in the study: low-risk controls (LRC), high risk for ASD (HRA; infants with older sibling with ASD) without ASD, and HRA infants who later receive a diagnosis of ASD (ASD). Event-related potentials (ERPs) to speech sounds were recorded at 12 months. Utilizing a novel observational approach, handedness was measured by hand preference on a variety of behaviors at 36 months. Results: At 12 months, lateralization patterns of ERPs to speech stimuli differed across the groups with the ASD group showing reversed lateralization compared to the LRC group. At 36 months, factor analysis of behavioral observations of hand preferences indicated a one-factor model with medium to high factor loadings. A composite handedness score was derived; no group differences were observed. There was no association between lateralization to speech at 12 months and handedness at 36 months in the LRC and HRA groups. However, children with ASD did show an association such that infants with lateralization patterns more similar to the LRC group at 12 months were stronger right-handers at 36 months. Conclusions: These results highlight early developmental patterns that might be specific to ASD, including a potential early biomarker of reversed lateralization to speech stimuli at 12 months, and a relation between behavioral and neural asymmetries. Future investigations of early asymmetry patterns, especially atypical hemispheric specialization, may be informative in the early identification of ASD

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

Neural indices and looking behaviors of audiovisual speech processing in infancy and early childhood

Language is a multimodal process with visual and auditory cues playing important roles in understanding speech. A well-controlled paradigm with audiovisually matched and mismatched syllables is often used to capture audiovisual (AV) speech processing. The ability to detect and integrate mismatching cues shows large individual variability across development and is linked to later language in typical development (TD) and social abilities in autism spectrum disorder (ASD). However, no study has used a multimethod approach to better understand AV speech processing in early development. The studies’ aims were to examine behavioral performance, gaze patterns, and neural indices of AV speech in: 1) TD preschoolers (N=60; females=35) and 2) infants at risk for developing ASD (high-risk, HR; N=37; females=10) and TD controls (low-risk, LR; N=42; females=21). In Study 1, I investigated preschoolers’ gaze patterns and behavioral performance when presented with matched and mismatched AV speech and visual-only (lipreading) speech. As hypothesized, lipreading abilities were associated with children’s ability to integrate mismatching AV cues, and children looked towards the mouth when visual cues were helpful, specifically in lipreading conditions. Unexpectedly, looking time towards the mouth was not associated with the children’s ability to integrate mismatching AV cues. Study 2 examined how visual cues of AV speech modulated auditory event-related potentials (ERPs), and associations between ERPs and preschoolers’ behavioral performance during an AV speech task. As hypothesized, the auditory ERPs were attenuated during AV speech compared to auditory-only speech. Additionally, individual differences in their neural processing of auditory and visual cues predicted which cue the child attended to in mismatched AV speech. In Study 3, I investigated ERPs of AV speech in LR and HR 12-month-olds and their association with language abilities at 18-months. Unexpectedly, I found no group differences: all infants were able to detect mismatched AV speech as measured through a more negative ERP response. As hypothesized, more mature neural processing of AV speech integration, measured as a more positive ERP response to fusible AV cues, predicted later language across all infants. These results highlight the importance of using multimethod approaches to understand variability in AV speech processing at two developmental stages.2021-11-12T00:00:00

Adaptive NKG2C+ natural killer cells are related to exacerbations and nutritional abnormalities in COPD patients

Abstract: Chronic obstructive pulmonary disease (COPD) is a chronic and often progressive disorder with a heterogeneous presentation and frequent systemic manifestations. Several aspects like persistence in smoking habit, continuous exacerbations, alpha-1-antitrypsin deficiency and inflammatory-immune response, are involved in the pathophysiology and progression of the disease. However, the role of natural killer (NK) cells remains controversial. Otherwise, human cytomegalovirus (HCMV) infection has been reported to induce an adaptive differentiation and expansion of an NK cell subset which carries the CD94/NKG2C receptor, which may contribute to an upset immune defense. For these reasons, our objective is to assess the distribution of NK cells and their subset in COPD patients and some of its phenotypes. Methods: Peripheral blood samples were obtained from 66 COPD patients. HCMV serology and the proportions of total NK cells and the NKG2C+ and NKG2A+ subsets were evaluated by flow cytometry. The NKG2C genotype was also assessed. Results: Eighty-eight per cent of COPD patients were HCMV(+), and the proportions of total NK cells were higher in patients with severe-very severe airway obstruction than in those with only mild-moderate involvement. There were no differences in the proportions of NKG2C+ cells between controls and COPD, either among COPD patients classified by severity of the disease. However, the percentage of NKG2C+ cells were higher in COPD patients with frequent exacerbations than in occasional exacerbators, and higher in cases with reduced lean mass (Fat free mass index) than in those with normal nutritional status. Conclusion: These results suggest a relationship between levels of NKG2C+ cells in COPD patients and clinical variables closely linked to a poor/worse prognosis.SEPAR 2015, MINECO Plan Estatal I + D Retos (SAF2013–49063-C2–1-R, SAF2016–80363-C2–1-R y SAF2014–54371) (FEDER Funds), FUCAP & Menarini

Same data, different analysts: variation in effect sizes due to analytical decisions in ecology and evolutionary biology

Gould E, Fraser H, Parker T, et al. Same data, different analysts: variation in effect sizes due to analytical decisions in ecology and evolutionary biology. 2023.Although variation in effect sizes and predicted values among studies of similar phenomena is inevitable, such variation far exceeds what might be produced by sampling error alone. One possible explanation for variation among results is differences among researchers in the decisions they make regarding statistical analyses. A growing array of studies has explored this analytical variability in different (mostly social science) fields, and has found substantial variability among results, despite analysts having the same data and research question. We implemented an analogous study in ecology and evolutionary biology, fields in which there have been no empirical exploration of the variation in effect sizes or model predictions generated by the analytical decisions of different researchers. We used two unpublished datasets, one from evolutionary ecology (blue tit, Cyanistes caeruleus, to compare sibling number and nestling growth) and one from conservation ecology (Eucalyptus, to compare grass cover and tree seedling recruitment), and the project leaders recruited 174 analyst teams, comprising 246 analysts, to investigate the answers to prespecified research questions. Analyses conducted by these teams yielded 141 usable effects for the blue tit dataset, and 85 usable effects for the Eucalyptus dataset. We found substantial heterogeneity among results for both datasets, although the patterns of variation differed between them. For the blue tit analyses, the average effect was convincingly negative, with less growth for nestlings living with more siblings, but there was near continuous variation in effect size from large negative effects to effects near zero, and even effects crossing the traditional threshold of statistical significance in the opposite direction. In contrast, the average relationship between grass cover and Eucalyptus seedling number was only slightly negative and not convincingly different from zero, and most effects ranged from weakly negative to weakly positive, with about a third of effects crossing the traditional threshold of significance in one direction or the other. However, there were also several striking outliers in the Eucalyptus dataset, with effects far from zero. For both datasets, we found substantial variation in the variable selection and random effects structures among analyses, as well as in the ratings of the analytical methods by peer reviewers, but we found no strong relationship between any of these and deviation from the meta-analytic mean. In other words, analyses with results that were far from the mean were no more or less likely to have dissimilar variable sets, use random effects in their models, or receive poor peer reviews than those analyses that found results that were close to the mean. The existence of substantial variability among analysis outcomes raises important questions about how ecologists and evolutionary biologists should interpret published results, and how they should conduct analyses in the future

Empagliflozin in Patients with Chronic Kidney Disease

Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m(2) of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m(2) with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to < 10 ml per minute per 1.73 m(2), a sustained decrease in eGFR of & GE;40% from baseline, or death from renal causes) or death from cardiovascular causes. Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P < 0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P=0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups. Conclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo