Association of smoking and nicotine dependence with pre-diabetes in young and healthy adults.

INTRODUCTION: Several studies have shown an increased risk of type 2 diabetes among smokers. Therefore, the aim of this analysis was to assess the relationship between smoking, cumulative smoking exposure and nicotine dependence with pre-diabetes. METHODS: We performed a cross-sectional analysis of healthy adults aged 25-41 in the Principality of Liechtenstein. Individuals with known diabetes, Body Mass Index (BMI) >35 kg/m² and prevalent cardiovascular disease were excluded. Smoking behaviour was assessed by self-report. Pre-diabetes was defined as glycosylated haemoglobin between 5.7% and 6.4%. Multivariable logistic regression models were done. RESULTS: Of the 2142 participants (median age 37 years), 499 (23.3%) had pre-diabetes. There were 1,168 (55%) never smokers, 503 (23%) past smokers and 471 (22%) current smokers, with a prevalence of pre-diabetes of 21.2%, 20.9% and 31.2%, respectively (p <0.0001). In multivariable regression models, current smokers had an odds ratio (OR) of pre-diabetes of 1.82 (95% confidential interval (CI) 1.39; 2.38, p <0.0001). Individuals with a smoking exposure of <5, 5-10 and >10 pack-years had an OR (95% CI) for pre-diabetes of 1.34 (0.90; 2.00), 1.80 (1.07; 3.01) and 2.51 (1.80; 3.59) (p linear trend <0.0001) compared with never smokers. A Fagerström score of 2, 3-5 and >5 among current smokers was associated with an OR (95% CI) for pre-diabetes of 1.27 (0.89; 1.82), 2.15 (1.48; 3.13) and 3.35 (1.73; 6.48) (p linear trend <0.0001). DISCUSSION: Smoking is strongly associated with pre-diabetes in young adults with a low burden of smoking exposure. Nicotine dependence could be a potential mechanism of this relationship

Prospective Assessment of Sex-Related Differences in Symptom Status and Health Perception Among Patients With Atrial Fibrillation.

We prospectively assessed sex-specific differences in health perception, overall symptom status, and specific symptoms in a large cohort of patients with atrial fibrillation. We performed a prospective multicenter observational cohort study of 1553 patients with atrial fibrillation. Patients completed questionnaires about personal characteristics, comorbidities, and symptoms on a yearly basis. Mean age was 70±11 years among women and 67±12 years among men. Health perception on a visual analogue scale ranging from 0 to 100 (with higher scores indicating better health perception) was significantly lower in women than in men (70 [interquartile range: 50-80] versus 75 [interquartile range: 60-85]; javax.xml.bind.JAXBElement@29592a5d <0.0001). More women than men had any symptoms (85.0% versus 68.3%; javax.xml.bind.JAXBElement@7ac0b4e4 <0.0001), palpitations (65.2% versus 44.4%; javax.xml.bind.JAXBElement@41229466 <0.0001), dizziness (25.6% versus 13.5%; javax.xml.bind.JAXBElement@61871784 <0.0001), dyspnea (35.7% versus 21.8%; javax.xml.bind.JAXBElement@16cc22b <0.0001), and fatigue (25.3% versus 19.1%; javax.xml.bind.JAXBElement@7ef43176 =0.006). At 1-year follow-up, symptoms decreased in both sexes but remained more frequent in women (49.1% versus 32.6%, javax.xml.bind.JAXBElement@2b200b6a <0.0001). In multivariable adjusted longitudinal regression models, female sex remained an independent predictor for lower health perception (ß=-4.8; 95% CI, -6.5 to -3.1; javax.xml.bind.JAXBElement@72c212bd <0.0001), any symptoms (odds ratio [OR]: 2.6; 95% CI, 2.1-3.4; javax.xml.bind.JAXBElement@15d8fb54 <0.0001), palpitations (OR: 2.6; 95% CI, 2.1-3.2; javax.xml.bind.JAXBElement@4af80718 <0.0001), dizziness (OR: 2.9; 95% CI, 2.1-3.9; javax.xml.bind.JAXBElement@61282e76 <0.0001), dyspnea (OR: 2.1; 95% CI, 1.6-2.8; javax.xml.bind.JAXBElement@31d9f14 <0.0001), fatigue (OR: 1.6; 95% CI, 1.2-2.2; javax.xml.bind.JAXBElement@51cdd678 =0.0008), and chest pain (OR: 1.8; 95% CI, 1.3-2.6; javax.xml.bind.JAXBElement@5b87db9e =0.001). Women with atrial fibrillation have a substantially higher symptom burden and lower health perception than men. These relationships persisted after multivariable adjustment and during prospective follow-up

MuPix7 - A fast monolithic HV-CMOS pixel chip for Mu3e

The MuPix7 chip is a monolithic HV-CMOS pixel chip, thinned down to 50 \mu m. It provides continuous self-triggered, non-shuttered readout at rates up to 30 Mhits/chip of 3x3 mm^2 active area and a pixel size of 103x80 \mu m^2. The hit efficiency depends on the chosen working point. Settings with a power consumption of 300 mW/cm^2 allow for a hit efficiency >99.5%. A time resolution of 14.2 ns (Gaussian sigma) is achieved. Latest results from 2016 test beam campaigns are shown.Comment: Proceedingsfor the PIXEL2016 conference, submitted to JINST A dangling reference has been removed from this version, no other change

Amount of Information Needed for Model Choice in Approximate Bayesian Computation

Approximate Bayesian Computation (ABC) has become a popular technique in evolutionary genetics for elucidating population structure and history due to its flexibility. The statistical inference framework has benefited from significant progress in recent years. In population genetics, however, its outcome depends heavily on the amount of information in the dataset, whether that be the level of genetic variation or the number of samples and loci. Here we look at the power to reject a simple constant population size coalescent model in favor of a bottleneck model in datasets of varying quality. Not only is this power dependent on the number of samples and loci, but it also depends strongly on the level of nucleotide diversity in the observed dataset. Whilst overall model choice in an ABC setting is fairly powerful and quite conservative with regard to false positives, detecting weaker bottlenecks is problematic in smaller or less genetically diverse datasets and limits the inferences possible in non-model organism where the amount of information regarding the two models is often limited. Our results show it is important to consider these limitations when performing an ABC analysis and that studies should perform simulations based on the size and nature of the dataset in order to fully assess the power of the study

Automated Quantification of QT-Intervals by an Algorithm : A Validation Study in Patients with Chronic Obstructive Pulmonary Disease

Study objectives To assess the diagnostic accuracy of a purpose-designed QTc-scoring algorithm versus the established hand-scoring in patients with chronic obstructive pulmonary disease (COPD) undergoing sleep studies. Methods We collected 62 overnight electrocardiogram (ECG) recordings in 28 COPD patients. QT-intervals corrected for heart rate (QTc, Bazett) were averaged over 1-min periods and quantified, both by the algorithm and by cursor-assisted hand-scoring. Hand-scoring was done blinded to the algorithm-derived results. Bland-Altman statistics and confusion matrixes for three thresholds (460, 480, and 500ms) were calculated. Results A total of 32944 1-min periods and corresponding mean QTc-intervals were analysed manually and by computer. Mean difference between manual and algorithm-based QTc-intervals was -1ms, with limits of agreement of -18 to 16ms. Overall, 2587 (8%), 357 (1%), and 0 QTc-intervals exceeding the threshold 460, 480, and 500ms, respectively, were identified by hand-scoring. Of these, 2516, 357, and 0 were consistently identified by the algorithm. This resulted in a diagnostic classification accuracy of 0.98 (95% CI 0.98/0.98), 1.00 (1.00/1.00), and 1.00 (1.00/1.00) for 460, 480, and 500ms, respectively. Sensitivity was 0.97, 1.00, and NA for 460, 480, and 500ms, respectively. Specificity was 0.98, 1.00, and 1.00 for 460, 480, and 500ms, respectively. Conclusion Overall, 8% of nocturnal 1-min periods showed clinically relevant QTc prolongations in patients with stable COPD. The automated QTc-algorithm accurately identified clinically relevant QTc-prolongations with a very high sensitivity and specificity. Using this tool, hospital sleep laboratories may identify asymptomatic patients with QTc-prolongations at risk for malignant arrhythmia, allowing them to consult a cardiologist before an eventual cardiac event

The role of ureteric indocyanine green fluorescence in colorectal surgery: a retrospective cohort study.

BACKGROUND Ureteric injury (UI) is an infrequent but serious complication of colorectal surgery. Prophylactic ureteric stenting is employed to avoid UI, yet its efficacy remains debated. Intraoperative indocyanine green fluorescence imaging (ICG-FI) has been used to facilitate ureter detection. This study aimed to investigate the role of ICG-FI in identification of ureters during colorectal surgery and its impact on the incidence of UI. METHODS A retrospective cohort study involving 556 consecutive patients who underwent colorectal surgery between 2018 and 2023 assessed the utility of routine prophylactic ureteric stenting with adjunctive ICG-FI. Patients with ICG-FI were compared to those without ICG-FI. Demographic data, operative details, and postoperative morbidity were analyzed. Statistical analysis included univariable regression. RESULTS Ureteric ICG-FI was used in 312 (56.1%) patients, whereas 43.9% were controls. Both groups were comparable in terms of demographics except for a higher prevalence of prior abdominal surgeries in the ICG-FI group. Although intraoperative visualization was significantly higher in the ICG-FI group (95.3% vs 89.1%; p = 0.011), the incidence of UI was similar between groups (0.3% vs 0.8%; p = 0.585). Postoperative complications were similar between the two groups. Median stent insertion time was longer in the ICG-FI group (32 vs 25 min; p = 0.001). CONCLUSION Ureteric ICG-FI improved intraoperative visualization of the ureters but was not associated with a reduced UI rate. Median stent insertion time increased with use of ureteric ICG-FI, but total operative time did not. Despite its limitations, this study is the largest of its kind suggesting that ureteric ICG-FI may be a valuable adjunct to facilitate  ureteric visualization during colorectal surgery

Electron shuttle-mediated microbial Fe(III) reduction under alkaline conditions

Purpose: Extracellular Fe(III) reduction plays an important role in a variety of biogeochemical processes. Several mechanisms for microbial Fe(III) reduction in pH-neutral environments have been proposed, but pathways of microbial Fe(III) reduction within alkaline conditions have not been clearly identified. Alkaline soils are vastly distributed; thus, a better understanding of microbial Fe(III) reduction under alkaline conditions is of significance. The purpose of this study is to explore the dominant mechanism of bacterial iron reduction in alkaline environments. Materials and methods: We used antraquinone-2,6-disulfonate (AQDS) as a representative of quinone moities of humic substances and elemental sulfur and sulfate as sulfur species to investigate the potential role of humic substances and sulfur species in mediating microbial Fe(III) reduction in alkaline environments. We carried out thermodynamic calculations to predict the ability of bacteria to reduce Fe(III) (oxyhydr)oxides under alkaline conditions and the ability of AQDS and sulfur species to serve as electron acceptors for microbial anaerobic respiration in an assumed alkaline soil environments. A series of incubation experiments with two model dissimilatory metal reducing bacteria, Shewanella oneidensis MR-1 and Geobacter sulfurreducens PCA as well as mixed bacteria enriched from a soil were performed to confirm the contribution of AQDS and sulfur species to Fe(III) reduction under alkaline conditions. Results and discussion: Based on thermodynamic calculations, we predicted that, under alkaline conditions, the enzymatic reduction of Fe(III) (oxyhydr)oxides would be thermodynamically feasible but very weak. In our incubation experiments, the reduction of ferrihydrite by anaerobic cultures of Shewanella oneidensis MR-1, Geobacter sulfurreducens PCA or microbes enriched from a soil was significantly increased in the presence of S0 or AQDS. Notably, AQDS contributed more to promoting Fe(III) reduction as a soluble electron shuttle than S0 did under the alkaline conditions probably because of different mechanisms of microbial utilization of AQDS and S0. Conclusions: These results suggest that microbial reduction of Fe(III) (oxyhydr)oxides under alkaline conditions may proceed via a pathway mediated by electron shuttles such as AQDS and S0. Considering the high ability of electron shuttling and vast distribution of humic substances, we suggest that humic substance-mediated Fe(III) reduction may potentially be the dominant mechanism for Fe(III) reduction in alkaline environments

Importance of incomplete lineage sorting and introgression in the origin of shared genetic variation between two closely related pines with overlapping distributions

Genetic variation shared between closely related species may be due to retention of ancestral polymorphisms because of incomplete lineage sorting (ILS) and/or introgression following secondary contact. It is challenging to distinguish ILS and introgression because they generate similar patterns of shared genetic diversity, but this is nonetheless essential for inferring accurately the history of species with overlapping distributions. To address this issue, we sequenced 33 independent intron loci across the genome of two closely related pine species (Pinus massoniana Lamb. and Pinus hwangshanensis Hisa) from Southeast China. Population structure analyses revealed that the species showed slightly more admixture in parapatric populations than in allopatric populations. Levels of interspecific differentiation were lower in parapatry than in allopatry. Approximate Bayesian computation suggested that the most likely speciation scenario explaining this pattern was a long period of isolation followed by a secondary contact. Ecological niche modeling suggested that a gradual range expansion of P. hwangshanensis during the Pleistocene climatic oscillations could have been the cause of the overlap. Our study therefore suggests that secondary introgression, rather than ILS, explains most of the shared nuclear genomic variation between these two species and demonstrates the complementarity of population genetics and ecological niche modeling in understanding gene flow history. Finally, we discuss the importance of contrasting results from markers with different dynamics of migration, namely nuclear, chloroplast and mitochondrial DNA

Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation

Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death. Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups. To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 17,931 individuals with atrial fibrillation and 115,142 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases and 132,086 referents. We identified 12 new genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate the identification of new potential targets for drug discovery