Diabetes status and post-load plasma glucose concentration in relation to site-specific cancer mortality: findings from the original Whitehall study

ObjectiveWhile several studies have reported on the relation of diabetes status with pancreatic cancer risk, the predictive value of this disorder for other malignancies is unclear. Methods: The Whitehall study, a 25year follow-up for mortality experience of 18,006 men with data on post-challenge blood glucose and self-reported diabetes, allowed us to address these issues. Results: There were 2158 cancer deaths at follow-up. Of the 15 cancer outcomes, diabetes status was positively associated with mortality from carcinoma of the pancreas and liver, while the relationship with lung cancer was inverse, after controlling for a range of potential covariates and mediators which included obesity and socioeconomic position. After excluding deaths occurring in the first 10years of follow-up to examine the effect of reverse causality, the magnitude of the relationships for carcinoma of the pancreas and lung was little altered, while for liver cancer it was markedly attenuated. Conclusions: In the present study, diabetes status was related to pancreatic, liver, and lung cancer risk. Cohorts with serially collected data on blood glucose and covariates are required to further examine this area

Development of a primary care-based complex care management intervention for chronically ill patients at high risk for hospitalization: a study protocol

Background: Complex care management is seen as an approach to face the challenges of an ageing society with increasing numbers of patients with complex care needs. The Medical Research Council in the United Kingdom has proposed a framework for the development and evaluation of complex interventions that will be used to develop and evaluate a primary care-based complex care management program for chronically ill patients at high risk for future hospitalization in Germany. Methods and design: We present a multi-method procedure to develop a complex care management program to implement interventions aimed at reducing potentially avoidable hospitalizations for primary care patients with type 2 diabetes mellitus, chronic obstructive pulmonary disease, or chronic heart failure and a high likelihood of hospitalization. The procedure will start with reflection about underlying precipitating factors of hospitalizations and how they may be targeted by the planned intervention (pre-clinical phase). An intervention model will then be developed (phase I) based on theory, literature, and exploratory studies (phase II). Exploratory studies are planned that entail the recruitment of 200 patients from 10 general practices. Eligible patients will be identified using two ways of 'case finding': software based predictive modelling and physicians' proposal of patients based on clinical experience. The resulting subpopulations will be compared regarding healthcare utilization, care needs and resources using insurance claims data, a patient survey, and chart review. Qualitative studies with healthcare professionals and patients will be undertaken to identify potential barriers and enablers for optimal performance of the complex care management program. Discussion: This multi-method procedure will support the development of a primary care-based care management program enabling the implementation of interventions that will potentially reduce avoidable hospitalizations

Syndromics: A Bioinformatics Approach for Neurotrauma Research

Substantial scientific progress has been made in the past 50 years in delineating many of the biological mechanisms involved in the primary and secondary injuries following trauma to the spinal cord and brain. These advances have highlighted numerous potential therapeutic approaches that may help restore function after injury. Despite these advances, bench-to-bedside translation has remained elusive. Translational testing of novel therapies requires standardized measures of function for comparison across different laboratories, paradigms, and species. Although numerous functional assessments have been developed in animal models, it remains unclear how to best integrate this information to describe the complete translational “syndrome” produced by neurotrauma. The present paper describes a multivariate statistical framework for integrating diverse neurotrauma data and reviews the few papers to date that have taken an information-intensive approach for basic neurotrauma research. We argue that these papers can be described as the seminal works of a new field that we call “syndromics”, which aim to apply informatics tools to disease models to characterize the full set of mechanistic inter-relationships from multi-scale data. In the future, centralized databases of raw neurotrauma data will enable better syndromic approaches and aid future translational research, leading to more efficient testing regimens and more clinically relevant findings

Measurement of the nuclear modification factor for muons from charm and bottom hadrons in Pb+Pb collisions at 5.02 TeV with the ATLAS detector

Heavy-flavour hadron production provides information about the transport properties and microscopic structure of the quark-gluon plasma created in ultra-relativistic heavy-ion collisions. A measurement of the muons from semileptonic decays of charm and bottom hadrons produced in Pb+Pb and pp collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV with the ATLAS detector at the Large Hadron Collider is presented. The Pb+Pb data were collected in 2015 and 2018 with sampled integrated luminosities of 208 mu b(-1) and 38 mu b(-1), respectively, and pp data with a sampled integrated luminosity of 1.17 pb(-1) were collected in 2017. Muons from heavy-flavour semileptonic decays are separated from the light-flavour hadronic background using the momentum imbalance between the inner detector and muon spectrometer measurements, and muons originating from charm and bottom decays are further separated via the muon track's transverse impact parameter. Differential yields in Pb+Pb collisions and differential cross sections in pp collisions for such muons are measured as a function of muon transverse momentum from 4 GeV to 30 GeV in the absolute pseudorapidity interval vertical bar eta vertical bar < 2. Nuclear modification factors for charm and bottom muons are presented as a function of muon transverse momentum in intervals of Pb+Pb collision centrality. The bottom muon results are the most precise measurement of b quark nuclear modification at low transverse momentum where reconstruction of B hadrons is challenging. The measured nuclear modification factors quantify a significant suppression of the yields of muons from decays of charm and bottom hadrons, with stronger effects for muons from charm hadron decays

A search for an unexpected asymmetry in the production of e+μ− and e−μ+ pairs in proton-proton collisions recorded by the ATLAS detector at root s = 13 TeV

This search, a type not previously performed at ATLAS, uses a comparison of the production cross sections for e(+)mu(-) and e(-)mu(+) pairs to constrain physics processes beyond the Standard Model. It uses 139 fb(-1) of proton-proton collision data recorded at root s = 13 TeV at the LHC. Targeting sources of new physics which prefer final states containing e(+)mu(-) and e(-)mu(+), the search contains two broad signal regions which are used to provide model-independent constraints on the ratio of cross sections at the 2% level. The search also has two special selections targeting supersymmetric models and leptoquark signatures. Observations using one of these selections are able to exclude, at 95% confidence level, singly produced smuons with masses up to 640 GeV in a model in which the only other light sparticle is a neutralino when the R-parity-violating coupling lambda(23)(1)' is close to unity. Observations using the other selection exclude scalar leptoquarks with masses below 1880 GeV when g(1R)(eu) = g(1R)(mu c) = 1, at 95% confidence level. The limit on the coupling reduces to g(1R)(eu) = g(1R)(mu c) = 0.46 for a mass of 1420 GeV

Differential cross-section measurements of the production of four charged leptons in association with two jets using the ATLAS detector

Differential cross-sections are measured for the production of four charged leptons in association with two jets. These measurements are sensitive to final states in which the jets are produced via the strong interaction as well as to the purely-electroweak vector boson scattering process. The analysis is performed using proton-proton collision data collected by ATLAS at √s = 13 TeV and with an integrated luminosity of 140 fb−1. The data are corrected for the effects of detector inefficiency and resolution and are compared to state-of-the-art Monte Carlo event generator predictions. The differential cross-sections are used to search for anomalous weak-boson self-interactions that are induced by dimension-six and dimension-eight operators in Standard Model effective field theory