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In the European Union, the escalating generation of waste, together with the difficulties in finding new places for its disposal, have led to choose for incineration as an alternative to the management of non-reusable or recyclable waste, recovering it and generating energy. The incineration of waste, however, generates a series of contaminants that have been associated with effects on human health and the environment. Several studies have analysed the impact produced by energy recovery plants, by comparing the concentration of pollutants both in air and in biological samples donated by the population living near and far from these facilities. A notable limitation in existing research is the scarcity of baseline data on dioxins, furans, and PCBs in air and in the general population prior to the plant ́s start of operations. Such data facilitates meaningful comparisons with post-start-up levels. This article delineates the methodology employed to assess the impact on air quality and public health resulting from the implementation of an energy recovery facility through an urban waste incineration (waste-to-energy plant) in Gipuzkoa, located in the Basque Country, Spain. This methodology includes the measurement of the levels of contaminants in air, the level of exposure of the population by measuring the body load of contaminants, and the concentrations in soil and locally produced food. Furthermore, the health status of the population has been evaluated in both the short and long term, as well as the assessment of the risk from exposure to air pollution.

* Context.--Discrete submucosal necrotic nodules may rarely manifest as colon polyps. Objective.--To characterize the clinical and pathologic features of this lesion, which has been under-studied in the literature. Design.--We conducted an international search to compile a series. For each potential case, photomicrographs were centrally reviewed to confirm the diagnosis. We gathered clinical and pathologic information on each confirmed case. Results.--The final cohort included 25 patients, with 23 having 1 lesion and 2 having several (31 lesions total). Mean patient age was 62 years; 13 patients (52%) were male. Symptoms were nonspecific, although 4 patients (16%) had blood in stool; 14 patients were asymptomatic. Patient history and medications appeared noncontributory. Most cases were located in the right colon (n = 18; 58%). Mean lesion size was 0.4 cm (range, 0.1-1.7 cm). Histology typically showed a centrally necrotic nodule with peripheral fibrosis, chronic inflammation, and sometimes palisading granulomatous inflammation. Percent necrosis ranged from 5% to 95% (average, 70%), and percent fibrosis ranged from 3% to 70% (average, 25%). In 3 cases, degenerated parasitic structures consistent with Anisakis could be seen on hematoxylin-eosin and trichrome special stain. No patient experienced disease recurrence. Conclusions.--Submucosal necrotic nodules can present as colon polyps. Most cases are unifocal, and patients do well on follow-up. At least some examples appear to be caused by Anisakis, implicating patient diet. Patients are often asymptomatic, and many cases show no histologic evidence of the causative agent. doi: 10.5858/arpa.2022-0267-OA, Colon polyps are a relatively common finding on colonoscopy and are usually biopsied or excised for pathologic evaluation. (1) Most of these polyps represent epithelial proliferations involving the mucosal surface [...]

Abstract Background Higher maternal pre-pregnancy body mass index (BMI) is associated with adverse pregnancy and perinatal outcomes. However, whether these associations are causal remains unclear. Methods We explored the relation of maternal pre-/early-pregnancy BMI with 20 pregnancy and perinatal outcomes by integrating evidence from three different approaches (i.e. multivariable regression, Mendelian randomisation, and paternal negative control analyses), including data from over 400,000 women. Results All three analytical approaches supported associations of higher maternal BMI with lower odds of maternal anaemia, delivering a small-for-gestational-age baby and initiating breastfeeding, but higher odds of hypertensive disorders of pregnancy, gestational hypertension, preeclampsia, gestational diabetes, pre-labour membrane rupture, induction of labour, caesarean section, large-for-gestational age, high birthweight, low Apgar score at 1 min, and neonatal intensive care unit admission. For example, higher maternal BMI was associated with higher risk of gestational hypertension in multivariable regression (OR = 1.67; 95% CI = 1.63, 1.70 per standard unit in BMI) and Mendelian randomisation (OR = 1.59; 95% CI = 1.38, 1.83), which was not seen for paternal BMI (OR = 1.01; 95% CI = 0.98, 1.04). Findings did not support a relation between maternal BMI and perinatal depression. For other outcomes, evidence was inconclusive due to inconsistencies across the applied approaches or substantial imprecision in effect estimates from Mendelian randomisation. Conclusions Our findings support a causal role for maternal pre-/early-pregnancy BMI on 14 out of 20 adverse pregnancy and perinatal outcomes. Pre-conception interventions to support women maintaining a healthy BMI may reduce the burden of obstetric and neonatal complications. Funding Medical Research Council, British Heart Foundation, European Research Council, National Institutes of Health, National Institute for Health Research, Research Council of Norway, Wellcome Trust.

Abstract Sleep duration has been linked to a wide range of negative health outcomes and to reduced life expectancy. We present genome-wide association studies of short ( ≤ 5 h) and long ( ≥ 10 h) sleep duration in adults of European (N = 445,966), African (N = 27,785), East Asian (N = 3141), and admixed-American (N = 16,250) ancestry from UK Biobank and the Million Veteran Programme. In a cross-population meta-analysis, we identify 84 independent loci for short sleep and 1 for long sleep. We estimate SNP-based heritability for both sleep traits in each ancestry based on population derived linkage disequilibrium (LD) scores using cov-LDSC. We identify positive genetic correlation between short and long sleep traits (rg = 0.16 ± 0.04; p = 0.0002), as well as similar patterns of genetic correlation with other psychiatric and cardiometabolic phenotypes. Mendelian randomisation reveals a directional causal relationship between short sleep and depression, and a bidirectional causal relationship between long sleep and depression.

Abstract Background Systemic and local profiles have each been associated with asthma, but parsing causal relationships between system-wide and airway-specific processes can be challenging. We sought to investigate systemic and airway processes in asthma and their causal relationships. Methods Three hundred forty-one participants with persistent asthma and non-asthmatic controls were recruited and underwent peripheral blood mononuclear cell (PBMC) collection and nasal brushing. Transcriptome-wide RNA sequencing of the PBMC and nasal samples and a series of analyses were then performed using a discovery and independent test set approach at each step to ensure rigor. Analytic steps included differential expression analyses, coexpression and probabilistic causal (Bayesian) network constructions, key driver analyses, and causal mediation models. Results Among the 341 participants, the median age was 13 years (IQR = 10–16), 164 (48%) were female, and 200 (58.7%) had persistent asthma with mean Asthma Control Test (ACT) score 16.6 (SD = 4.2). PBMC genes associated with asthma were enriched in co-expression modules for NK cell-mediated cytotoxicity (fold enrichment = 4.5, FDR = 6.47 × 10−32) and interleukin production (fold enrichment = 2.0, FDR = 1.01 × 10−15). Probabilistic causal network and key driver analyses identified NK cell granule protein (NKG7, fold change = 22.7, FDR = 1.02 × 10−31) and perforin (PRF1, fold change = 14.9, FDR = 1.31 × 10−22) as key drivers predicted to causally regulate PBMC asthma modules. Nasal genes associated with asthma were enriched in the tricarboxylic acid (TCA) cycle module (fold enrichment = 7.5 FDR = 5.09 × 10−107), with network analyses identifying G3BP stress granule assembly factor 1 (G3BP1, fold change = 9.1 FDR = 2.77 × 10−5) and InaD-like protein (INADL, fold change = 5.3 FDR = 2.98 × 10−9) as nasal key drivers. Causal mediation analyses revealed that associations between PBMC key drivers and asthma are causally mediated by nasal key drivers (FDR = 0.0076 to 0.015). Conclusions Integrated study of the systemic and airway transcriptomes in a well-phenotyped asthma cohort identified causal key drivers of asthma among PBMC and nasal transcripts. Associations between PBMC key drivers and asthma are causally mediated by nasal key drivers.

Abstract Unravelling protein distributions within individual cells is vital to understanding their function and state and indispensable to developing new treatments. Here we present the Hybrid subCellular Protein Localiser (HCPL), which learns from weakly labelled data to robustly localise single-cell subcellular protein patterns. It comprises innovative DNN architectures exploiting wavelet filters and learnt parametric activations that successfully tackle drastic cell variability. HCPL features correlation-based ensembling of novel architectures that boosts performance and aids generalisation. Large-scale data annotation is made feasible by our AI-trains-AI approach, which determines the visual integrity of cells and emphasises reliable labels for efficient training. In the Human Protein Atlas context, we demonstrate that HCPL is best performing in the single-cell classification of protein localisation patterns. To better understand the inner workings of HCPL and assess its biological relevance, we analyse the contributions of each system component and dissect the emergent features from which the localisation predictions are derived.

Once a patient has been diagnosed with severe COVID-19 pneumonia, treatment options have limited effectiveness. Opaganib is an oral treatment under investigation being evaluated for treatment of hospitalized patients with severe COVID-19 pneumonia. A randomized, placebo-controlled, double-blind phase 2/3 trial was conducted in 57 sites worldwide from August 2020 to July 2021. Patients received either opaganib (n = 230; 500 mg twice daily) or matching placebo (n = 233) for 14 days. The primary outcome was the proportion of patients no longer requiring supplemental oxygen by day 14. Secondary outcomes included changes in the World Health Organization Ordinal Scale for Clinical Improvement, viral clearance, intubation, and mortality at 28 and 42 days. Pre-specified primary and secondary outcome analyses did not demonstrate statistically significant benefit (except nominally for time to viral clearance). Post-hoc analysis revealed the fraction of inspired oxygen (FIO2) at baseline was prognostic for opaganib treatment responsiveness and corresponded to disease severity markers. Patients with FIO2 levels at or below the median value (≤60%) had better outcomes after opaganib treatment (n = 117) compared to placebo (n = 134). The proportion of patients with ≤60% FIO2 at baseline that no longer required supplemental oxygen (≥24 h) by day 14 of opaganib treatment increased (76.9% vs. 63.4%; nominal p-value = 0.033). There was a 62.6% reduction in intubation/mechanical ventilation (6.84% vs. 17.91%; nominal p-value = 0.012) and a clinically meaningful 62% reduction in mortality (5.98% vs. 16.7%; nominal p-value = 0.019) by day 42. No new safety concerns were observed. While the primary analyses were not statistically significant, post-hoc analysis suggests opaganib benefit for patients with severe COVID-19 requiring supplemental oxygen with an FIO2 of ≤60%. Further studies are warranted to prospectively confirm opaganib benefit in this subpopulation.

This paper introduces an LC resonator-based single-frequency eddy current (EC) sensor designed for corrosion detection in reinforcing bars (rebars) embedded within concrete structures. The work addresses the challenges of the limited detection ranges and reduced sensitivity over longer distances, prevalent in current EC sensor applications. The sensor development process involved a systematic experimental approach to carefully selecting each parameter in the LC resonator. The sensor design aimed to assess the condition of the rebar from a distance of up to 5–6 cm outside the concrete and provide insights into different corrosion levels. By examining the characteristics of the inductors, the parallel resistance Rp of the eddy current coil was identified as a key parameter reflecting the corrosion conditions in the rebar. The relationship between the Rp fluctuations and temperature variations was investigated, with the data indicating that an approximately 155 Ω variation can be expected per 1 °C change within the temperature range of 20–25 °C, allowing for temperature compensation if necessary. Subsequently, the sensor’s performance was evaluated by placing a rebar within a concrete block, where controlled mechanical degradation cycles were applied to simulate uniform corrosion in the rebar. The experimental results show that our EC sensor can detect material loss around the rebar with accuracy of approximately 0.17 mm.

The burden of large and rare copy number genetic variants (CNVs) as well as certain specific CNVs increase the risk of developing schizophrenia. Several cognitive measures are purported schizophrenia endophenotypes and may represent an intermediate point between genetics and the illness. This paper investigates the influence of CNVs on cognition. We conducted a systematic review and meta-analysis of the literature exploring the effect of CNV burden on general intelligence. We included ten primary studies with a total of 18,847 participants and found no evidence of association. In a new psychosis family study, we investigated the effects of CNVs on specific cognitive abilities. We examined the burden of large and rare CNVs (>200 kb,

Abstract Aims Police employees may experience high levels of stress due to the challenging nature of their work which can then lead to sickness absence. To date, there has been limited research on sickness absence in the police. This exploratory analysis investigated sickness absence in UK police employees. Methods Secondary data analyses were conducted using data from the Airwave Health Monitoring Study (2006–2015). Past year sickness absence was self-reported and categorised as none, low (1–5 days), moderate (6–19 days) and long-term sickness absence (LTSA, 20 or more days). Descriptive statistics and multinomial logistic regressions were used to examine sickness absence and exploratory associations with sociodemographic factors, occupational stressors, health risk behaviours, and mental health outcomes, controlling for rank, gender and age. Results From a sample of 40,343 police staff and police officers, forty-six per cent had no sickness absence within the previous year, 33% had a low amount, 13% a moderate amount and 8% were on LTSA. The groups that were more likely to take sick leave were women, non-uniformed police staff, divorced or separated, smokers and those with three or more general practitioner consultations in the past year, poorer mental health, low job satisfaction and high job strain. Conclusions The study highlights the groups of police employees who may be more likely to take sick leave and is unique in its use of a large cohort of police employees. The findings emphasise the importance of considering possible modifiable factors that may contribute to sickness absence in UK police forces.

In energy systems' economic models, people's behaviour is often underestimated, and they are generally unaware of how habits impact energy efficiency. Improving efficiency is challenging, and recommendations alone may not be sufficient. Changing behaviour requires understanding the direct impact of needs and habits on energy efficiency. This research introduces a methodology that retrieves human expert knowledge from four key aspects of the current energy transition: everyday appliances, buildings, mobility, flexibility, and energy efficiency. The aim is to examine the causal relationship between energy consumption and human behaviour, gaining a deeper understanding of the links among the factors that drive final energy consumers to change habits through the adoption of energy-saving measures. Working in collaboration with expert panels, this study provides a methodology for extracting expert human knowledge based on a set of future energy transition scenarios aligned with the achievement of the Paris Agreement, a taxonomy of 32 factors that have a strong influence on households' investment decisions, and the results of a survey that characterises the European population through the 32-factor taxonomy and some socioeconomic conditions. In addition, the survey included a sample of the Latin American population to analyse how socioeconomic conditions (region, education, gender, etc.) influence the prioritisation of these factors. We discuss the high priority given to competence and autonomy over financial factors by inhabitants of the European Union residential sector. We provide an analysis of the factors through which other similar projects are focused and on which we converge. In addition, we contribute by presenting the hierarchy of priorities assigned by people. This highlights the importance for policymakers to take these aspects seriously when implementing energy policy interventions that go beyond purely financial measures and fiscal incentives.

BackgroundHealthcare professionals work in high-pressured and demanding environments, which has been linked to the use of alcohol as a coping strategy. This international review aimed (i) to determine the pooled prevalence of hazardous, harmful, dependent, and frequent binge drinking in healthcare professionals, and (ii) to explore factors associated with variation in these outcomes.MethodsScopus, MEDLINE, and PsycINFO were searched from 2003 to 17th November 2022, for studies reporting a prevalence estimate for any outcome among healthcare professionals. Random-effects meta-analyses determined pooled prevalence estimates. Sub-group analyses were conducted, stratifying the meta-analyses by pandemic period vs pre-pandemic period. Meta-regressions explored factors that were associated with variation in the outcomes. PROSPERO (CRD42020173119).ResultsAfter screening 9,108 records, 64 studies were identified as eligible. The pooled prevalence was 19.98% [95% Confidence Intervals [CI]: 16.05–24.23%] for hazardous alcohol use (K = 52), 3.17% [95% CI: 0.95–6.58%] for harmful drinking (K = 8), 14.59% [95% CI: 7.16–25.05%] for dependent drinking (K = 7), and 17.71% [95% CI: 8.34–29.63%] for frequent binge drinking (K = 11). The prevalence of hazardous drinking was greater during the pandemic (28.19%) compared with pre-pandemic estimates (17.95%), though this was not statistically significant (p = 0.049). Studies including all hospital staff (32.04%) showed higher prevalence estimates for hazardous drinking compared with studies of doctors (16.78%) and nurses (27.02%).ConclusionApproximately one fifth of healthcare professionals drink to hazardous levels, with higher prevalence estimates observed during the COVID-19 pandemic. It may be that healthcare professionals used alcohol to cope with the additional trauma and stressors. Further research is needed to investigate whether this is sustained in the post-pandemic period.