Quality of colonoscopy in an organised colorectal cancer screening programme with immunochemical faecal occult blood test. The EQuIPE study (Evaluating Quality Indicators of the Performance of Endoscopy)

OBJECTIVES: To assess variation in the main colonoscopy quality indicators in organised colorectal cancer (CRC) screening programmes based on faecal immunochemical test (FIT). DESIGN: Data from a case-series of colonoscopies of FIT-positive subjects were provided by 44 Italian CRC screening programmes. Data on screening history, endoscopic procedure and histology results, and additional information on the endoscopy centre and the endoscopists were collected. The adenoma detection rate (ADR) and caecal intubation rate (CIR) were assessed for the whole population and the individual endoscopists. To explore variation in the quality indicators, multilevel analyses were performed according to patient/centre/endoscopist characteristics. RESULTS: We analysed 75 569 (mean age: 61.3 years; men: 57%) colonoscopies for positive FIT performed by 479 endoscopists in 79 centres. ADR ranged from 13.5% to 75% among endoscopists (mean: 44.8%). ADR was associated with gastroenterology specialty (OR: 0.87 for others, 95% CI 0.76 to 0.96) and, at the endoscopy centre level, with the routine use of sedation (OR: 0.80 if occasional (600 colonoscopies; 95% CI 1.11 to 2.04) and, at the endoscopy centre level, screening-dedicated sessions (OR: 2.18; 95% CI 1.24 to 3.83) and higher rates of sedation (OR: 0.47 if occasional; 95% CI 0.24 to 0.92). CONCLUSIONS: The quality of colonoscopy was affected by patient-related, endoscopist-related and centre-related characteristics. Policies addressing organisational issues should improve the quality of colonoscopy in our programme and similar programmes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions

Exposure to Perfluoroalkyl Substances and Mortality for COVID-19: A Spatial Ecological Analysis in the Veneto Region (Italy).

BACKGROUND: In the context of the COVID-19 pandemic, there is interest in assessing if per- and polyfluoroalkyl substances (PFAS) exposures are associated with any increased risk of COVID-19 or its severity, given the evidence of immunosuppression by some PFAS. The objective of this paper is to evaluate at the ecological level if a large area (Red Zone) of the Veneto Region, where residents were exposed for decades to drinking water contaminated by PFAS, showed higher mortality for COVID-19 than the rest of the region. METHODS: We fitted a Bayesian ecological regression model with spatially and not spatially structured random components on COVID-19 mortality at the municipality level (period between 21 February and 15 April 2020). The model included education score, background all-cause mortality (for the years 2015-2019), and an indicator for the Red Zone. The two random components are intended to adjust for potential hidden confounders. RESULTS: The COVID-19 crude mortality rate ratio for the Red Zone was 1.55 (90% Confidence Interval 1.25; 1.92). From the Bayesian ecological regression model adjusted for education level and baseline all-cause mortality, the rate ratio for the Red Zone was 1.60 (90% Credibility Interval 0.94; 2.51). CONCLUSION: In conclusion, we observed a higher mortality risk for COVID-19 in a population heavily exposed to PFAS, which was possibly explained by PFAS immunosuppression, bioaccumulation in lung tissue, or pre-existing disease being related to PFAS

The Collagen Chaperone HSP47 Is a New Interactor of APP that Affects the Levels of Extracellular Beta-Amyloid Peptides

Alzheimer disease (AD) is a neurodegenerative disorder characterized by progressive decline of cognitive function that represents one of the most dramatic medical challenges for the aging population. Aβ peptides, generated by processing of the Amyloid Precursor Protein (APP), are thought to play a central role in the pathogenesis of AD. However, the network of physical and functional interactions that may affect their production and deposition is still poorly understood. The use of a bioinformatic approach based on human/mouse conserved coexpression allowed us to identify a group of genes that display an expression profile strongly correlated with APP. Among the most prominent candidates, we investigated whether the collagen chaperone HSP47 could be functionally correlated with APP. We found that HSP47 accumulates in amyloid deposits of two different mouse models and of some AD patients, is capable to physically interact with APP and can be relocalized by APP overexpression. Notably, we found that it is possible to reduce the levels of secreted Aβ peptides by reducing the expression of HSP47 or by interfering with its activity via chemical inhibitors. Our data unveil HSP47 as a new functional interactor of APP and imply it as a potential target for preventing the formation and/or growth amyloid plaques

The gut microbiota of Colombians differs from that of Americans, Europeans and Asians

ABSTRACT: The composition of the gut microbiota has recently been associated with health and disease, particularly with obesity. Some studies suggested a higher proportion of Firmicutes and a lower proportion of Bacteroidetes in obese compared to lean people; others found discordant patterns. Most studies, however, focused on Americans or Europeans, giving a limited picture of the gut microbiome. To determine the generality of previous observations and expand our knowledge of the human gut microbiota, it is important to replicate studies in overlooked populations. Thus, we describe here, for the first time, the gut microbiota of Colombian adults via the pyrosequencing of the 16S ribosomal DNA (rDNA), comparing it with results obtained in Americans, Europeans, Japanese and South Koreans, and testing the generality of previous observations concerning changes in Firmicutes and Bacteroidetes with increasing body mass index (BMI). Results: We found that the composition of the gut microbiota of Colombians was significantly different from that of Americans, Europeans and Asians. The geographic origin of the population explained more variance in the composition of this bacterial community than BMI or gender. Concerning changes in Firmicutes and Bacteroidetes with obesity, in Colombians we found a tendency in Firmicutes to diminish with increasing BMI, whereas no change was observed in Bacteroidetes. A similar result was found in Americans. A more detailed inspection of the Colombian dataset revealed that five fiber-degrading bacteria, including Akkermansia, Dialister, Oscillospira, Ruminococcaceae and Clostridiales, became less abundant in obese subjects. Conclusion: We contributed data from unstudied Colombians that showed that the geographic origin of the studied population had a greater impact on the composition of the gut microbiota than BMI or gender. Any strategy aiming to modulate or control obesity via manipulation of this bacterial community should consider this effect

Pyrosequencing as a tool for better understanding of human microbiomes

Next-generation sequencing technologies have revolutionized the analysis of microbial communities in diverse environments, including the human body. This article reviews several aspects of one of these technologies, the pyrosequencing technique, including its principles, applications, and significant contribution to the study of the human microbiome, with especial emphasis on the oral microbiome. The results brought about by pyrosequencing studies have significantly contributed to refining and augmenting the knowledge of the community membership and structure in and on the human body in healthy and diseased conditions. Because most oral infectious diseases are currently regarded as biofilm-related polymicrobial infections, high-throughput sequencing technologies have the potential to disclose specific patterns related to health or disease. Further advances in technology hold the perspective to have important implications in terms of accurate diagnosis and more effective preventive and therapeutic measures for common oral diseases

Report from Working Group 3: Beyond the standard model physics at the HL-LHC and HE-LHC

This is the third out of five chapters of the final report [1] of the Workshop on Physics at HL-LHC, and perspectives on HE-LHC [2]. It is devoted to the study of the potential, in the search for Beyond the Standard Model (BSM) physics, of the High Luminosity (HL) phase of the LHC, defined as $3$ ab$^{-1}$ of data taken at a centre-of-mass energy of 14 TeV, and of a possible future upgrade, the High Energy (HE) LHC, defined as $15$ ab$^{-1}$ of data at a centre-of-mass energy of 27 TeV. We consider a large variety of new physics models, both in a simplified model fashion and in a more model-dependent one. A long list of contributions from the theory and experimental (ATLAS, CMS, LHCb) communities have been collected and merged together to give a complete, wide, and consistent view of future prospects for BSM physics at the considered colliders. On top of the usual standard candles, such as supersymmetric simplified models and resonances, considered for the evaluation of future collider potentials, this report contains results on dark matter and dark sectors, long lived particles, leptoquarks, sterile neutrinos, axion-like particles, heavy scalars, vector-like quarks, and more. Particular attention is placed, especially in the study of the HL-LHC prospects, to the detector upgrades, the assessment of the future systematic uncertainties, and new experimental techniques. The general conclusion is that the HL-LHC, on top of allowing to extend the present LHC mass and coupling reach by $20-50\%$ on most new physics scenarios, will also be able to constrain, and potentially discover, new physics that is presently unconstrained. Moreover, compared to the HL-LHC, the reach in most observables will, generally more than double at the HE-LHC, which may represent a good candidate future facility for a final test of TeV-scale new physics

Supplement: "Localization and broadband follow-up of the gravitational-wave transient GW150914" (2016, ApJL, 826, L13)

This Supplement provides supporting material for Abbott et al. (2016a). We briefly summarize past electromagnetic (EM) follow-up efforts as well as the organization and policy of the current EM follow-up program. We compare the four probability sky maps produced for the gravitational-wave transient GW150914, and provide additional details of the EM follow-up observations that were performed in the different bands

Measurement of t(t)over-bar normalised multi-differential cross sections in pp collisions at root s=13 TeV, and simultaneous determination of the strong coupling strength, top quark pole mass, and parton distribution functions

Peer reviewe