Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Measurement of the inclusive isolated-photon cross section in pp collisions at √s = 13 TeV using 36 fb−1 of ATLAS data

The differential cross section for isolated-photon production in pp collisions is measured at a centre-of-mass energy of 13 TeV with the ATLAS detector at the LHC using an integrated luminosity of 36.1 fb. The differential cross section is presented as a function of the photon transverse energy in different regions of photon pseudorapidity. The differential cross section as a function of the absolute value of the photon pseudorapidity is also presented in different regions of photon transverse energy. Next-to-leading-order QCD calculations from Jetphox and Sherpa as well as next-to-next-to-leading-order QCD calculations from Nnlojet are compared with the measurement, using several parameterisations of the proton parton distribution functions. The predictions provide a good description of the data within the experimental and theoretical uncertainties. [Figure not available: see fulltext.

Obesity and type 2 diabetes susceptibility genes identified from recent genome-wide association studies: impact on Southern Chinese

Background and objectives: Recent genome-wide association (GWA) studies conducted in Caucasian populations have significantly expanded the list of confirmed and potential susceptibility genes for obesity and type 2 diabetes. The major objective of this thesis was to establish the role of the previously identified obesity- and T2DM-susceptibility genes in the Hong Kong Southern Chinese population. Major findings: In a cross-sectional case-control study of Southern Chinese which involved 470 obese cases and 700 normal-weight controls, significant associations with obesity were demonstrated in 7 of 13 single nucleotide polymorphisms (SNPs) that have shown significant associations with obesity and/or body mass index (BMI) in previous Caucasian GWA studies. These SNPs are located within or near the GNPDA2, FTO, MC4R, KCTD15, SFRS10-ETV5-DGKG, SEC16B-RASAL2 and NEGR1 loci. The combined genetic risk score (GRS) of the 13 studied SNPs was associated with an increased risk for obesity. The GNPDA2 rs10938397, FTO rs8050136, and MC4R rs17782313, which showed the most significant associations with obesity, were further examined for their associations with persistent central obesity and the metabolic syndrome (MetS). Both rs8050136 and rs10938397 were significantly associated with persistent central obesity. rs10938397 was also associated with the MetS. The combined GRS of these 3 SNPs showed significant associations with both persistent central obesity and persistent MetS. Nineteen multimarker-tagging SNPs that span a well-defined LD block of the FTO gene were evaluated for their associations with obesity in a case-control study which involved 249 cases and 400 controls. rs16952522 was found to be significantly associated with obesity, in addition to the well-known SNP rs8050136. These 2 SNPs were nominally associated with T2DM, although the associations were abolished after adjustment for age, sex and BMI. However, the GA haplotype composed of the risk alleles of these 2 SNPs was significantly associated with T2DM, independent of BMI. Seventeen previously identified T2DM-associated SNPs were investigated for the associations with glycaemic progression in an 8-year follow-up study which involved 518 cases and 998 controls. Their combined GRS was associated with an increased risk for glycaemic progression. A significant association with glycaemic progression was found with CDKN2A/B rs10811661. Moreover, KCNJ11 rs5219 and IGF2BP2 rs11711477 also showed potential associations with glycaemic progression. In the subsequent 12-year follow-up study, which involved 200 cases and 903 controls, the CDKN2A/B rs10811661 showed a significant independent association with incident T2DM. The KCNJ11 E23K (rs5219) variant was examined for its association with diabetes development in a 12-year prospective study. It was found to be significantly associated with the development of prediabetes but not with the development of T2DM. However, in a meta-analysis which involved 15680 subjects across different populations, this variant could indeed predict T2DM. Conclusions: The findings of this thesis have provided novel evidence supporting the role of the GWA studies-identified obesity- and T2DM-associated genetic variants as genetic markers of obesity and T2DM among Southern Chinese in Hong Kong, and suggest that the GNPDA2, FTO and MC4R genes confer susceptibility to obesity and that the CDKN2A/B and KCNJ11 genes may play a role in diabetes development.published_or_final_versionMedicineDoctoralDoctor of Philosoph

Evaluation of fracture risk among type 2 diabetes patients with non-valvular atrial fibrillation receiving different oral anticoagulants

   Objective: Patients with type 2 diabetes are at higher fracture risk owing to the attenuated bone turnover and impaired bone microarchitecture. The comparative effect of warfarin over non-vitamin K antagonist oral anticoagulants (NOACs) on incident fractures among patients with type 2 diabetes comorbid with atrial fibrillation (AF) remains to be elucidated. Research Design and Methods: This was a retrospective propensity-score weighted population-based cohort study of adults with type 2 diabetes and AF who were started on warfarin or NOAC between 2005 and 2019, identified from the electronic database of the Hong Kong Hospital Authority. The primary outcome was a composite of major osteoporotic fractures (hip, clinical vertebral, proximal humerus and wrist). Hazard ratios (HR) were calculated using Cox proportional hazard regression models. Results: 15,770 type 2 diabetes patients comorbid with AF were included (9,288 on NOAC and 6,482 on warfarin). During a median follow-up of 20 months, 551 patients (3.5%) sustained major osteoporotic fractures (201 in NOAC group [2.2%]; 350 in warfarin group [5.4%]). The adjusted cumulative incidence was lower among NOAC users than warfarin users (HR 0.80, 95% CI 0.64-0.99, p=0.044). Subgroup analyses showed consistent protective effects against major osteoporotic fractures among NOAC users across sex, age, HbA1c, duration of diabetes and history of severe hypoglycemia, compared with warfarin users.  Conclusions: NOAC use was associated with a lower risk of major osteoporotic fractures than warfarin use, among type 2 diabetes patients comorbid with AF. NOAC may be the preferred anticoagulant from the perspective of bone health.</p

Exome-wide association analysis reveals novel coding sequence variants associated with lipid traits in Chinese

Blood lipids are important risk factors for coronary artery disease (CAD). Here we perform an exome-wide association study by genotyping 12,685 Chinese, using a custom Illumina HumanExome BeadChip, to identify additional loci influencing lipid levels. Single-variant association analysis on 65,671 single nucleotide polymorphisms reveals 19 loci associated with lipids at exome-wide significance (P<2.69 × 10−7), including three Asian-specific coding variants in known genes (CETP p.Asp459Gly, PCSK9 p.Arg93Cys and LDLR p.Arg257Trp). Furthermore, missense variants at two novel loci—PNPLA3 p.Ile148Met and PKD1L3 p.Thr429Ser—also influence levels of triglycerides and low-density lipoprotein cholesterol, respectively. Another novel gene, TEAD2, is found to be associated with high-density lipoprotein cholesterol through gene-based association analysis. Most of these newly identified coding variants show suggestive association (P<0.05) with CAD. These findings demonstrate that exome-wide genotyping on samples of non-European ancestry can identify additional population-specific possible causal variants, shedding light on novel lipid biology and CAD

A polygenic risk score improves risk stratification of coronary artery disease: a large-scale prospective Chinese cohort study

10.1093/eurheartj/ehac093EUROPEAN HEART JOURNAL43181702-

Empagliflozin in Patients with Chronic Kidney Disease

Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m(2) of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m(2) with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to &lt; 10 ml per minute per 1.73 m(2), a sustained decrease in eGFR of &amp; GE;40% from baseline, or death from renal causes) or death from cardiovascular causes. Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P &lt; 0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P=0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups. Conclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo

Measurements of ttˉt\bar{t} differential cross-sections of highly boosted top quarks decaying to all-hadronic final states in pppp collisions at s=13 \sqrt{s}=13\, TeV using the ATLAS detector

Measurements are made of differential cross-sections of highly boosted pair-produced top quarks as a function of top-quark and $t\bar{t}$ system kinematic observables using proton--proton collisions at a center-of-mass energy of $\sqrt{s} = 13$ TeV. The data set corresponds to an integrated luminosity of $36.1$ fb$^{-1}$, recorded in 2015 and 2016 with the ATLAS detector at the CERN Large Hadron Collider. Events with two large-radius jets in the final state, one with transverse momentum $p_{\rm T} > 500$ GeV and a second with $p_{\rm T}>350$ GeV, are used for the measurement. The top-quark candidates are separated from the multijet background using jet substructure information and association with a $b$-tagged jet. The measured spectra are corrected for detector effects to a particle-level fiducial phase space and a parton-level limited phase space, and are compared to several Monte Carlo simulations by means of calculated $\chi^2$ values. The cross-section for $t\bar{t}$ production in the fiducial phase-space region is $292 \pm 7 \ \rm{(stat)} \pm 76 \rm{(syst)}$ fb, to be compared to the theoretical prediction of $384 \pm 36$ fb