Trajectories of body mass index in adulthood and risk of subtypes of postmenopausal breast cancer

Background - Body fatness is a dynamic exposure throughout life. To provide more insight into the association between body mass index (BMI) and postmenopausal breast cancer, we aimed to examine the age at onset, duration, intensity, and trajectories of body fatness in adulthood in relation to risk of breast cancer subtypes. Methods - Based on self-reported anthropometry in the prospective Norwegian Women and Cancer Study, we calculated the age at onset, duration, and intensity of overweight and obesity using linear mixed-effects models. BMI trajectories in adulthood were modeled using group-based trajectory modeling. We used Cox proportional hazards models to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for the associations between BMI exposures and breast cancer subtypes in 148,866 postmenopausal women. Results - A total of 7223 incident invasive postmenopausal breast cancer cases occurred during follow-up. Increased overweight duration and age at the onset of overweight or obesity were associated with luminal A-like breast cancer. Significant heterogeneity was observed in the association between age at overweight and overweight duration and the intrinsic-like subtypes (pheterogeneity 0.03). Compared with women who remained at normal weight throughout adulthood, women with a descending BMI trajectory had a reduced risk of luminal A-like breast cancer (HR 0.54, 95% CI 0.33–0.90), whereas women with ascending BMI trajectories were at increased risk (HR 1.09; 95% CI 1.01–1.17 for “Normal-overweight”; HR 1.20; 95% CI 1.07–1.33 for “Normal-obesity”). Overweight duration and weighted cumulative years of overweight and obesity were inversely associated with luminal B-like breast cancer. Conclusions - In this exploratory analysis, decreasing body fatness from obesity in adulthood was inversely associated with overall, hormone receptor-positive and luminal A-like breast cancer in postmenopausal women. This study highlights the potential health benefits of reducing weight in adulthood and the health risks associated with increasing weight throughout adult life. Moreover, our data provide evidence of intrinsic-like tumor heterogeneity with regard to age at onset and duration of overweight

Immuno-fluorescent Labeling of Microtubules and Centrosomal Proteins in Ex Vivo Intestinal Tissue and 3D In Vitro Intestinal Organoids.

The advent of 3D in vitro organoids that mimic the in vivo tissue architecture and morphogenesis has greatly advanced the ability to study key biological questions in cell and developmental biology. In addition, organoids together with recent technical advances in gene editing and viral gene delivery promises to advance medical research and development of new drugs for treatment of diseases. Organoids grown in vitro in basement matrix provide powerful model systems for studying the behavior and function of various proteins and are well suited for live-imaging of fluorescent-tagged proteins. However, establishing the expression and localization of the endogenous proteins in ex vivo tissue and in in vitro organoids is important to verify the behavior of the tagged proteins. To this end we have developed and modified tissue isolation, fixation, and immuno-labeling protocols for localization of microtubules, centrosomal, and associated proteins in ex vivo intestinal tissue and in in vitro intestinal organoids. The aim was for the fixative to preserve the 3D architecture of the organoids/tissue while also preserving antibody antigenicity and enabling good penetration and clearance of fixative and antibodies. Exposure to cold depolymerizes all but stable microtubules and this was a key factor when modifying the various protocols. We found that increasing the ethylenediaminetetraacetic acid (EDTA) concentration from 3 mM to 30 mM gave efficient detachment of villi and crypts in the small intestine while 3 mM EDTA was sufficient for colonic crypts. The developed formaldehyde/methanol fixation protocol gave very good structural preservation while also preserving antigenicity for effective labeling of microtubules, actin, and the end-binding (EB) proteins. It also worked for the centrosomal protein ninein although the methanol protocol worked more consistently. We further established that fixation and immuno-labeling of microtubules and associated proteins could be achieved with organoids isolated from or remaining within the basement matrix

Candidate Personality Traits Associated with Ratings in a Military Officer Selection Setting

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Predictors of long time survival after lung cancer surgery. A retrospective cohort study.

Background: There have been few reports regarding long time survival after lung cancer surgery. The influence of age and pulmonary function on long time survival is still not fully discovered. Some reports suggest that hospitals with a high surgical volume have better results. The aim of this study was to evaluate lung cancer surgery performed in a county hospital in terms of 30 days mortality, complications and predictors of long time survival. Methods: All patients operated with non-small cell lung cancer in the period 1993–2006 were reviewed, and 148 patients were included in the study. 30 days mortality and complications were analyzed by univariate analysis. Kaplan Meier plots were performed to display some of the univariate variables. Cox regression analysis was performed to find Hazard Ratios (HR) that predicted long time survival in univariate and multivariate analysis. Results: The overall 30 days mortality rate was 2.7%, whereas 36.3% had one or more complications after surgery. The median survival time was 3.4 years. In multivariate Cox regression analysis advanced preoperative stage predicted reduced long time survival with HR (95%CI) 1.63 (0.92, 2.89) and 4.16 (1.92, 9.05) for patients in stage IB and II-IV respectively, when compared to patients in stage IA. Age ≥ 70 years and FEV1<80% predicted reduced long time survival with HR (95%CI) 2.23 (1.41, 3.54) and 1.93 (1.14, 3.28) respectively, compared to age<70 years and FEV1 ≥ 80%. Conclusion: Thirty days mortality and complication rate showed that lung cancer surgery can be performed safely in a county hospital with experienced thoracic surgeons. Early preoperative stage, age below 70 years and normal pulmonary function predicted long time survival.publishedVersio

Direct and indirect effects of socioeconomic status on sepsis risk and mortality : a mediation analysis of the HUNT Study

Author's accepted version (postprint).This is an Accepted Manuscript of an article published by BMJ in Journal of Epidemiology and Community Health on 9/2/2023.Available online: doi.org/10.1136/jech-2022-219825acceptedVersio

The accretion and spreading of matter on white dwarfs

For a slowly rotating non-magnetized white dwarf the accretion disk extends all the way to the star. Here the matter impacts and spreads towards the poles as new matter continuously piles up behind it. We have solved the 3d compressible Navier-Stokes equations on an axisymmetric grid to determine the structure of this boundary layer for different viscosities corresponding to different accretion rates. The high viscosity cases show a spreading BL which sets off a gravity wave in the surface matter. The accretion flow moves supersonically over the cusp making it susceptible to the rapid development of gravity wave and/or Kelvin-Helmholtz instabilities. This BL is optically thick and extends more than 30 degrees to either side of the disk plane after 3/4 of a Keplerian rotation period (t=19s). The low viscosity cases also show a spreading BL, but here the accretion flow does not set off gravity waves and it is optically thin.Comment: 6 pages, 5 figures, requires autart.cl

A role for the terminal C5-C9 complement pathway in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease characterized by damage to the alveolar epithelium, leading to fibrosis and excessive accumulation of extracellular matrix in the interstitium of the lung. In the present study we performed high-resolution proteomic profiling of bronchoalveolar lavage (BAL) from IPF patients and controls, and found that the complement pathway was highly upregulated in IPF. The proteins C5, C6, C7, C8, and C9, all of which are part of the complement end product, TCC, were all upregulated. We also found that TCC levels were increased in plasma among IPF patients compared to controls, after adjustment for age, sex and BMI [mean (SD) 0.62 (0.24) vs. 0.33 (0.10), p = 0.031]. These findings suggest a role for the complement system in the pathogenesis of IPF

Trends in mortality after a sepsis hospitalization : a nationwide prospective registry study from 2008 to 2021

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