Novel associations for hypothyroidism include known autoimmune risk loci

Hypothyroidism is the most common thyroid disorder, affecting about 5% of the general population. Here we present the first large genome-wide association study of hypothyroidism, in 2,564 cases and 24,448 controls from the customer base of 23andMe, Inc., a personal genetics company. We identify four genome-wide significant associations, two of which are well known to be involved with a large spectrum of autoimmune diseases: rs6679677 near _PTPN22_ and rs3184504 in _SH2B3_ (p-values 3.5e-13 and 3.0e-11, respectively). We also report associations with rs4915077 near _VAV3_ (p-value 8.3e-11), another gene involved in immune function, and rs965513 near _FOXE1_ (p-value 3.1e-14). Of these, the association with _PTPN22_ confirms a recent small candidate gene study, and _FOXE1_ was previously known to be associated with thyroid-stimulating hormone (TSH) levels. Although _SH2B3_ has been previously linked with a number of autoimmune diseases, this is the first report of its association with thyroid disease. The _VAV3_ association is novel. These results suggest heterogeneity in the genetic etiology of hypothyroidism, implicating genes involved in both autoimmune disorders and thyroid function. Using a genetic risk profile score based on the top association from each of the four genome-wide significant regions in our study, the relative risk between the highest and lowest deciles of genetic risk is 2.1

Clinical efficacy and satisfaction of a digital wheeze detector in a multicentre randomised controlled trial: the WheezeScan study.

INTRODUCTION: Wheezing is common in preschool children and its clinical assessment often challenging for caretakers. This study aims to evaluate the impact of a novel digital wheeze detector (WheezeScan™) on disease control in a home care setting. METHODS: A multicentre randomised open-label controlled trial was conducted in Berlin, Istanbul and London. Participants aged 4-84 months with a doctor's diagnosis of recurrent wheezing in the past 12 months were included. While the control group followed usual care, the intervention group received the WheezeScan™ for at-home use for 120 days. Parents completed questionnaires regarding their child's respiratory symptoms, disease-related and parental quality of life, and caretaker self-efficacy at baseline (T0), 90 days (T1) and 4 months (T2). RESULTS: A total of 167 children, with a mean±sd age of 3.2±1.6 years, were enrolled in the study (intervention group n=87; control group n=80). There was no statistically significant difference in wheeze control assessed by TRACK (mean difference 3.8, 95% CI -2.3-9.9; p=0.2) at T1 between treatment groups (primary outcome). Children's and parental quality of life and parental self-efficacy were comparable between both groups at T1. The evaluation of device usability and perception showed that parents found it useful. CONCLUSION: In the current study population, the wheeze detector did not show significant impact on the home management of preschool wheezing. Hence, further research is needed to better understand how the perception and usage behaviour may influence the clinical impact of a digital support

Emergent quantum confinement at topological insulator surfaces

Bismuth-chalchogenides are model examples of three-dimensional topological insulators. Their ideal bulk-truncated surface hosts a single spin-helical surface state, which is the simplest possible surface electronic structure allowed by their non-trivial $\mathbb{Z}_2$ topology. They are therefore widely regarded ideal templates to realize the predicted exotic phenomena and applications of this topological surface state. However, real surfaces of such compounds, even if kept in ultra-high vacuum, rapidly develop a much more complex electronic structure whose origin and properties have proved controversial. Here, we demonstrate that a conceptually simple model, implementing a semiconductor-like band bending in a parameter-free tight-binding supercell calculation, can quantitatively explain the entire measured hierarchy of electronic states. In combination with circular dichroism in angle-resolved photoemission (ARPES) experiments, we further uncover a rich three-dimensional spin texture of this surface electronic system, resulting from the non-trivial topology of the bulk band structure. Moreover, our study reveals how the full surface-bulk connectivity in topological insulators is modified by quantum confinement.Comment: 9 pages, including supplementary information, 4+4 figures. A high resolution version is available at http://www.st-andrews.ac.uk/~pdk6/pub_files/TI_quant_conf_high_res.pd

Smoking Cessation after Diagnosis of New-Onset Atrial Fibrillation and the Risk of Stroke and Death

Limited data are available regarding the impact of smoking cessation after atrial fibrillation (AF) diagnosis on clinical outcomes. Using the Korean National Health Insurance Service database, we included patients newly diagnosed with AF and categorized them into four groups as follows: (i) never smokers, (ii) ex-smokers, (iii) smoking cessation after AF diagnosis (“quitters”), and (iv) current smokers. The primary outcomes were incident ischemic stroke and all-cause death during follow-up. Fatal ischemic stroke and death from cerebrovascular events were evaluated as secondary outcomes. Among 97,637 patients (mean age, 61 years; mean CHA(2)DS(2)-VASc score, 2.3), 6.9% stopped smoking after AF diagnosis. The mean follow-up duration was 3.2 ± 2.0 years. After multivariable adjustment, quitters had lower risks of ischemic stroke (hazard ratio (HR), 0.702; 95% confidence interval (CI), 0.595–0.827) and all-cause death (HR, 0.842; 95% CI, 0.748–0.948) than current smokers. Quitters after AF diagnosis were associated with lower risks of fatal ischemic stroke (HR, 0.454; 95% CI, 0.287–0.718) and death from cerebrovascular events (HR, 0.664; 95% CI, 0.465–0.949) compared with current smokers. Quitting smoking may reduce the risk of ischemic stroke, the severity of ischemic stroke, and the incidence of cerebrovascular events in patients with new-onset AF

Differences in External and Internal Cortical Strain with Prosthesis in the Femur

The contact between a femoral stem prosthesis and the internal surface of the cortical bone with the stress in the interface is of crucial importance with respect to loosening. However, there are no reports of strain patterns at this site, and the main aim of the current study was to investigate differences of internal and external cortical strain in the proximal femur after insertion of a stem prosthesis. The external cortical strain of a human cadaveric femur was measured with strain gauges before and after implantation of a stem prosthesis. By use of optical fibres embedded longitudinally in the endosteal cortex, deformations at the implant–internal cortex interface could also be measured. The main external deformation during loading of the intact femur occurred as compression of the medial cortex; both at the proximal and distal levels. The direction of the principal strain on the medial and lateral aspects was close to the longitudinal axis of the bone. After resection of the femoral neck and insertion of a stem prosthesis, the changes in external strain values were greatest medially at the proximal level, where the magnitude of deformation in compression was reduced to about half the values measured on the intact specimen. Otherwise, there were rather small changes in external principal strain. However, by comparing vertical strain in the external and internal cortex of the proximal femur, there were great differences in values and patterns at all positions. The transcortical differences in strain varied from compression on one side to distraction on the other and vice versa in some of the positions with a correlation coefficient of 0.07. Our results show that differences exist between the external and internal cortical strain when loading a stem prosthesis. Hence, strain at the internal cortex does not correspond and can not be deducted from measured strain at the external cortex

Evaluation of the Paradoxical Association Between Lipid Levels and Incident Atrial Fibrillation According to Statin Usage: A Nationwide Cohort Study.

ObjectiveHigher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) are associated with a lower risk of atrial fibrillation (AF). Statin use might exert confounding effects on the paradoxical associations; however, the relationships that distinguish statin users from non-users have not been thoroughly evaluated.MethodsFrom the Korean National Health Insurance Database, we included 9,778,014 adults who underwent a health examination in 2009. The levels of TC and LDL-C at the health examination were categorized into quartile values of the total study population. We grouped the study population into statin users and non-users and investigated the associations between TC, LDL-C, and the risk of incident AF.ResultsOf the total population, 867,336 (8.9%) were taking statins. During a mean follow-up of 8.2 years, inverse associations of TC - AF and LDL-C - AF were observed; higher levels of TC and LDL-C were associated with the lower risk of AF in the total population. Overall, statin users showed higher AF incidence rate than non-users, but the inverse associations of TC - AF and LDL-C - AF were consistently observed irrespective of statin usage; adjusted hazard ratio with 95% confidence interval was 0.81 (0.79-0.84) for statin users and 0.81 (0.80-0.83) for non-users in the highest TC quartile, and 0.84 (0.82-0.87) for statin users and 0.85 (0.84-0.86) for non-users in the highest LDL-C quartile (all pConclusionThe paradoxical relationship between lipid levels (TC and LDL-C) and the risk of AF remains consistent in both statin users and non-users