Restraint-induced Corticosterone Secretion and Hypothalamic CRH mRNA Expression are Augmented During Acute Withdrawal from Chronic Cocaine Administration

Stress responses during cocaine withdrawal likely contribute to drug relapse and may be intensified as a consequence of prior cocaine use. The present study examined changes in stressor-induced activation of the hypothalamic–pituitary–adrenal (HPA) axis during acute withdrawal from chronic cocaine administration. Adult male Sprague–Dawley rats received daily administration of cocaine (30 mg/kg, i.p.) or saline for 14 days. Twenty-four hours after the last injection, rats in each group were sacrificed under stress-free conditions or following 30 min of immobilization. Plasma corticosterone (CORT) was measured in trunk-blood using radioimmunoassay, corticotropin-releasing hormone (CRH) mRNA levels in the paraventricularnucleus (PVN) of the hypothalamus were measured using in situ hybridization and glucocorticoid receptor (GR) protein expression in the pituitary gland and dissected brain regions was measured using Western blot analysis. Basal CRH mRNA in the PVN was unaltered as a result of prior cocaine administration. However, a significant increase in CRH mRNA was observed 90 min following the termination of restraint in cocaine withdrawn, but not saline-treated, rats. Basal CORT was also unaffected by prior cocaine administration, but the CORT response measured immediately after restraint was significantly augmented in cocaine-withdrawn rats. Differences in GR protein expression in number of regions implicated in negative feedback regulation of HPA function, including the hypothalamus, were not observed. These findings indicate that the HPA response to stressors is intensified during early withdrawal from cocaine administration and may be independent of changes in GR-mediated negative feedback

Phage display selected magnetite interacting Adhirons for shape controlled nanoparticle synthesis

Adhirons are robust, well expressing, peptide display scaffold proteins, developed as an effective alternative to traditional antibody binding proteins for highly specific molecular recognition applications. This paper reports for the first time the use of these versatile proteins for material binding, and as tools for controlling material synthesis on the nanoscale. A phage library of Adhirons, each displaying two variable binding loops, was screened to identify specific proteins able to interact with [100] faces of cubic magnetite nanoparticles. The selected variable regions display a strong preference for basic residues such as lysine. Molecular dynamics simulations of amino acid adsorption onto a [100] magnetite surface provides a rationale for these interactions, with the lowest adsorption energy observed with lysine. These proteins direct the shape of the forming nanoparticles towards a cubic morphology in room temperature magnetite precipitation reactions, in stark contrast to the high temperature, harsh reaction conditions currently used to produce cubic nanoparticles. These effects demonstrate the utility of the selected Adhirons as novel magnetite mineralization control agents using ambient aqueous conditions. The approach we outline with artificial protein scaffolds has the potential to develop into a toolkit of novel additives for wider nanomaterial fabrication

Entry of copycats of luxury brands

We develop a game-theoretic model to examine the entry of copycats and its implications by incorporating two salient features; these features are two product attributes, i.e., physical resemblance and product quality, and two consumer utilities, i.e., consumption utility and status utility. Our equilibrium analysis suggests that copycats with a high physical resemblance but low product quality are more likely to successfully enter the market by defying the deterrence of the incumbent. Furthermore, we show that higher quality can prevent the copycat from successfully entering the market. Finally, we show that the entry of copycats does not always improve consumer surplus and social welfare. In particular, when the quality of the copycat is sufficiently low, the loss in status utility from consumers of the incumbent product overshadows the small gain in consumption utility from buyers of the copycat, leading to an overall decrease in consumer surplus and social welfare. </jats:p

Peripheral photoplethysmography variability analysis of sepsis patients

Sepsis is associated with impairment in autonomic regulatory function. This work investigates the application of heart rate and photoplethysmogram (PPG) waveform variability analysis in differentiating two categories of sepsis, namely systemic inflammatory response syndrome (SIRS) and severe sepsis. Electrocardiogram-derived heart period (RRi) and PPG waveforms, measured from fingertips (Fin-PPG) and earlobes (Ear-PPG), of Emergency Department sepsis patients (n = 28) with different disease severity, were analysed by spectral technique, and were compared to control subjects (n = 10) in supine and 80° head-up tilted positions. Analysis of covariance (ANCOVA) was applied to adjust for the confounding factor of age. Low-frequency (LF, 0.04-0.15 Hz), mid-frequency (MF, 0.09-0.15 Hz) and high-frequency (HF, 0.15-0.60 Hz) powers were computed. The normalised MF power in Ear-PPG (MFnu Ear) was significantly reduced in severe sepsis patients with hyperlactataemia (lactate > 2 mmol/l), compared to SIRS patients (P 0.05), suggesting that there may be a link between 0.1 Hz ear blood flow oscillation and tissue metabolic changes in sepsis, in addition to autonomic factors. The study highlighted the value of PPG spectral analysis in the non-invasive assessment of peripheral vascular regulation in sepsis patients, with potential implications in monitoring the progression of sepsis

Prevalence and determinants of home delivery in urban and rural Philippines: Evidence from the 2017 National Demographic and Health Survey

Background: Women’s choice of place of delivery has implications on maternal and child mortality. This study aims to provide an updated and detailed comparison of prevalence and determinants of home delivery in the Philippines, and in urban and rural communities. Methods: Based on data from the 2017 Philippine National Demographic and Health Survey (NDHS), we estimated the prevalence of home delivery and determined factors influencing women’s decision to deliver at home. Analyses were restricted to data from 7229 women who were cohabiting or married, and their last-born child using logistic regression methods for survey data. Results: There remain a considerable proportion of women aged 15–49 years old who delivered at home (17.92%(95% confidence interval (CI): 15.77; 20.30)). More women in rural areas delivered at home (23.53% (95% CI: 20.38, 26.99)) than their counterparts in urban areas (10.72% (95% CI: 8.23; 13.85)); reflecting a significant difference in the home delivery prevalence of women relative to their place of residence. Our regression analyses showed that there isa relatively greater effect observed for the rural population in most of the proximal factors considered including birth order, women’s decision-making power, and emergency preparedness during pregnancy. Wealth index has the most pronounced effect with a significant increase in odds of home delivery among urban and rural women of the lowest wealth categories. Conclusion: The use of institutional childbirth services remains suboptimal in the Philippines with significant disparities between urban and rural communities. Current strategies therefore need to adopt a multi-sectoral approach to address the complex factors influencing women’s decision on place of delivery. Targeted efforts specific to population groups should also be made to contextualize and co-create health care services and solutions that will motivate them to deliver in health facilities

Real-time COVID-19 hospital admissions forecasting with leading indicators and ensemble methods in England

Hospitalisations from COVID-19 with Omicron sub-lineages have put a sustained pressure on the English healthcare system. Understanding the expected healthcare demand enables more effective and timely planning from public health. We collect syndromic surveillance sources, which include online search data, NHS 111 telephonic and online triages. Incorporating this data we explore generalised additive models, generalised linear mixed-models, penalised generalised linear models and model ensemble methods to forecast over a two-week forecast horizon at an NHS Trust level. Furthermore, we showcase how model combinations improve forecast scoring through a mean ensemble, weighted ensemble, and ensemble by regression. Validated over multiple Omicron waves, at different spatial scales, we show that leading indicators can improve performance of forecasting models, particularly at epidemic changepoints. Using a variety of scoring rules, we show that ensemble approaches outperformed all individual models, providing higher performance at a 21-day window than the corresponding individual models at 14-days. We introduce a modelling structure used by public health officials in England in 2022 to inform NHS healthcare strategy and policy decision making. This paper explores the significance of ensemble methods to improve forecasting performance and how novel syndromic surveillance can be practically applied in epidemic forecasting

Respecting Autonomy and Enabling Diversity: The Effect of Eligibility and Enrollment on Research Data Demographics

Many promising advances in precision health and other Big Data research rely on large data sets to analyze correlations among genetic variants, behavior, environment, and outcomes to improve population health. But these data sets are generally populated with demographically homogeneous cohorts. We conducted a retrospective cohort study of patients at a major academic medical center during 2012–19 to explore how recruitment and enrollment approaches affected the demographic diversity of participants in its research biospecimen and data bank. We found that compared with the overall clinical population, patients who consented to enroll in the research data bank were significantly less diverse in terms of age, sex, race, ethnicity, and socioeconomic status. Compared with patients who were recruited for the data bank, patients who enrolled were younger and less likely to be Black or African American, Asian, or Hispanic. The overall demographic diversity of the data bank was affected as much (and in some cases more) by which patients were considered eligible for recruitment as by which patients consented to enroll. Our work underscores the need for systemic commitment to diversify data banks so that different communities can benefit from research

Ammonia in a time of COVID-19. A submission of evidence to Defra/AQEG

A submission to the Air Quality Expert Group (AQEG), an expert committee of the Department for Environment, Food and Rural Affairs (Defra) • Ammonia gas (NH3) is a priority pollutant both as a precursor to particulate matter and for ecosystem impacts. • Three scenarios for UK emission reductions during COVID-19 in emission sectors, where activity is likely reduced ,have been assessed. • Total UK emissions of NH3 are likely to have decreased slightly (~2%), which is within the uncertainty and meteorological variability of the UK atmosphere. • Urban background and urban on road and roadside emissions of NH3 are likely to have decreased, by as much as 30% and 90% respectively compared with usual emissions before COVID-19. • Unratified data from three of the five UK automatic NH3 analysers (Auchencorth Moss, Chilbolton Observatory, and Manchester OSCA Observatory) show typical springtime NH3 concentrations across the UK. • Data from the non-automatic National Ammonia Monitoring Network will enable analysis at UK level in the months ahead. This includes roadside data from London Cromwell Rd. • Evidence gaps & future approaches are outlined. Future analysis of the Defra UKEAP rural networks proposed. • The key measurement gap is urban roadside NH3 (and PM ammonium) as there is only one long-term site in the UK measuring roadside NH3 concentrations. It is suggested that a roadside network of samplers and/or analysers are urgently put in place (perhaps aligned with the UK Urban NO2 Network; UUNN) to monitor NH3 at roadsides during and post COVID-19 lock down where possible

Lessons Learned From Interdisciplinary Efforts to Combat COVID-19 Misinformation: Development of Agile Integrative Methods From Behavioral Science, Data Science, and Implementation Science

BACKGROUND: Despite increasing awareness about and advances in addressing social media misinformation, the free flow of false COVID-19 information has continued, affecting individuals\u27 preventive behaviors, including masking, testing, and vaccine uptake. OBJECTIVE: In this paper, we describe our multidisciplinary efforts with a specific focus on methods to (1) gather community needs, (2) develop interventions, and (3) conduct large-scale agile and rapid community assessments to examine and combat COVID-19 misinformation. METHODS: We used the Intervention Mapping framework to perform community needs assessment and develop theory-informed interventions. To supplement these rapid and responsive efforts through large-scale online social listening, we developed a novel methodological framework, comprising qualitative inquiry, computational methods, and quantitative network models to analyze publicly available social media data sets to model content-specific misinformation dynamics and guide content tailoring efforts. As part of community needs assessment, we conducted 11 semistructured interviews, 4 listening sessions, and 3 focus groups with community scientists. Further, we used our data repository with 416,927 COVID-19 social media posts to gather information diffusion patterns through digital channels. RESULTS: Our results from community needs assessment revealed the complex intertwining of personal, cultural, and social influences of misinformation on individual behaviors and engagement. Our social media interventions resulted in limited community engagement and indicated the need for consumer advocacy and influencer recruitment. The linking of theoretical constructs underlying health behaviors to COVID-19-related social media interactions through semantic and syntactic features using our computational models has revealed frequent interaction typologies in factual and misleading COVID-19 posts and indicated significant differences in network metrics such as degree. The performance of our deep learning classifiers was reasonable, with an F-measure of 0.80 for speech acts and 0.81 for behavior constructs. CONCLUSIONS: Our study highlights the strengths of community-based field studies and emphasizes the utility of large-scale social media data sets in enabling rapid intervention tailoring to adapt grassroots community interventions to thwart misinformation seeding and spread among minority communities. Implications for consumer advocacy, data governance, and industry incentives are discussed for the sustainable role of social media solutions in public health

Enhancing offspring hypothalamic-pituitary-adrenal (HPA) regulation via systematic novelty exposure: The influence of maternal HPA function

In the rat, repeated brief exposures to novelty early in life can induce long-lasting enhancements in adult cognitive, social, emotional, and neuroendocrine function. Family-to-family variations in these intervention effects on adult offspring are predicted by the mother's ability to mount a rapid corticosterone (CORT) response to the onset of an acute stressor. Here, in Long-Evans rats, we investigated whether neonatal and adulthood novelty exposure, each individually and in combination, can enhance offspring hypothalamic-pituitary-adrenal (HPA) regulation. Using a 2 × 2 within-litter design, one half of each litter were exposed to a relatively novel non-home environment for 3-min (Neo_Novel) daily during infancy (PND 1-21) and the other half of the litter remained in the home cage (Neo_Home); we further exposed half of these two groups to early adulthood (PND 54-63) novelty exposure in an open field and the remaining siblings stayed in their home cages. Two aspects of HPA regulation were assessed: the ability to maintain a low level of resting CORT (CORTB) and the ability to mount a large rapid CORT response (CORTE) to the onset of an acute stressor. Assessment of adult offspring's ability to regulate HPA regulation began at 370 days of age. We further investigated whether the novelty exposure effects on offspring HPA regulation are sensitive to the context of maternal HPA regulation by assessing maternal HPA regulation similarly beginning 7 days after her pups were weaned. We found that at the population level, rats receiving neonatal, but not early adulthood exposure or both, showed a greater rapid CORTE than their home-staying siblings. At the individual family level, these novelty effects are positively associated with maternal CORTE. These results suggest that early experience of novelty can enhance the offspring's ability to mount a rapid response to environmental challenge and the success of such early life intervention is critically dependent upon the context of maternal HPA regulation. © 2014 Dinces, Romeo, McEwen and Tang.Link_to_subscribed_fulltex