The genetic architecture of type 2 diabetes

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of heritability. To test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole genome sequencing in 2,657 Europeans with and without diabetes, and exome sequencing in a total of 12,940 subjects from five ancestral groups. To increase statistical power, we expanded sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support a major role for lower-frequency variants in predisposition to type 2 diabetes

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

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

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Operation and performance of the ATLAS semiconductor tracker in LHC Run 2

The semiconductor tracker (SCT) is one of the tracking systems for charged particles in the ATLAS detector. It consists of 4088 silicon strip sensor modules. During Run 2 (2015–2018) the Large Hadron Collider delivered an integrated luminosity of 156 fb-1 to the ATLAS experiment at a centre-of-mass proton-proton collision energy of 13 TeV. The instantaneous luminosity and pile-up conditions were far in excess of those assumed in the original design of the SCT detector. Due to improvements to the data acquisition system, the SCT operated stably throughout Run 2. It was available for 99.9% of the integrated luminosity and achieved a data-quality efficiency of 99.85%. Detailed studies have been made of the leakage current in SCT modules and the evolution of the full depletion voltage, which are used to study the impact of radiation damage to the modules

Performance of High-Speed Networks for Real-Time Applications

131 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1993.This thesis studies the performance of network medium-access protocols at high data transfer rates for real-time applications. In a real-time network, on-time delivery of messages is essential. We can ensure the timely completion of tasks only when we can predict the message transmission delay over the network reasonably well. For a given data transfer rate, whether messages in a network can be delivered in time depends on the medium-access protocols. The goal of this study is to determine the limitations in the ability of the protocols to guarantee on-time delivery of messages for different types of real-time applications. More specifically, we address the following two questions: (1) how well can traditional network medium-access protocols support real-time applications? and (2) how well do these protocols behave on a high-speed network?This thesis presents the results of a simulation study. The medium-access protocols studied are two token-passing protocols (token bus and token ring), the slotted-ring protocol and the multiple-ring protocols. The token-bus and token-ring protocols under our study are standards defined by the IEEE 802.4 and 802.5 recommendations, respectively, as well as by the fiber distributed data interface (FDDI). Besides the traditional performance measures, such as average message delay and throughput, our performance measures include the observed maximum message delay, number of messages missing their deadlines, and the variance in the message delay. The workloads for our experiments are based on typical real-time applications. One workload set is patterned after a distributed acoustic system on board a submarine. We also simulated two other real-time workload sets--the voice communication workload and the multi-media workload--to thoroughly investigate the performance of each of the network medium-access protocols.Our simulation results indicate how well each network medium-access protocol supports real-time applications of different workload characteristics. By understanding the desirable network parameters and the characteristics of the real-time workload, we can make it easier to decide which network medium-access protocol to use to support a real-time application on a high-speed network.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD

Integrated End-to-end Delay Analysis for Regulated ATM Networks

Abstract. In this paper, we present an ef®cient and effective method to derive the worst case end-to-end delay for ATM network.Traf®c and service description plays an important part in the end-to-end delay analysis.By utilizing the inverse of these arrival and service functions, we can effectively compute the worst case delay of an ATM switch.We analyze and compare the performance of an ATM switch with priority driven and FIFO scheduling policies using different workload sets and under different utilization.We also compare the performance using our proposed ``integrated&apos; &apos; method with the traditional ``independent&apos; &apos; method.From our simulation experiments, we found out that our method always produced a better estimation of cell delay within an ATM network

Using LDA Method to Provide Mobile Location Estimation Services within a Cellular Radio Network

Abstract — Mobile location estimation is becoming an important value-added service for a mobile phone operator. It is well-known that GPS can provide an accurate location estimation. But it is also a known fact that GPS does not perform well in urban areas like downtown New York and cities like Hong Kong. Then many mobile location estimation approaches based on the cellular radio networks have been proposed to compensate the problem of the lost of GPS signals for providing location services to mobile users in metropolitan areas, but there exists no general solution since each algorithm has its own advantage depending on specific terrain and environmental factors. In this paper, we propose a selector method with LDA among different kinds of mobile location estimation algorithms we had proposed in previous work to combine their merits, then provide a more accurate estimation for location services. And we build up a threelevel binary decision tree to classify these four algorithms. These three levels are named as Stat-Geo level, CG-nonCG level and CT-EPM level. And the success ratios of these three levels are 85.22%, 88.45 % and 88.89 % respectively. We have tested our selector method with real data taken in Hong Kong and the experiment results have shown that our selector method outperforms other existing location estimation algorithms among different kinds of terrains