A numerical investigation of moment coefficient and flow structure in a rotor-stator cavity with rotor mounted bolts

This paper presents a numerical study of the effect of rotor mounted bolts on the moment coefficient and flow structure within a rotor-stator cavity representative of modern gas turbine engine design. The CFD computations are performed using the commercial code FLUENT. The simulation methodology is first validated using experimental data from plain co-rotating disc and rotor-stator cavities from the open literature. Comparisons are then made with experimental data obtained from a test rig at the Thermo Fluid Mechanics Research Centre (TFMRC), University of Sussex. Computations were performed at Reφ = 6.8 × 106, Cw = 5929 (λT = 0.35) with different numbers of bolts (0 < N < 60), and also a continuous ring, at r/b = 0.9. The study has improved the current understanding of the effect on moment coefficient and flow structure that rotor mounted protrusions have in rotor-stator systems. It is seen that the contribution of skin friction to the moment coefficient reduces as the number of bolts is increased. The size and shape of the wake created by a rotating bolt also means that the pressure loss per bolt reduces with N but the overall effect is to increase the moment coefficient because there are more bolts. Copyright © 2011 by ASME

Virtual Constraints and Hybrid Zero Dynamics for Realizing Underactuated Bipedal Locomotion

Underactuation is ubiquitous in human locomotion and should be ubiquitous in bipedal robotic locomotion as well. This chapter presents a coherent theory for the design of feedback controllers that achieve stable walking gaits in underactuated bipedal robots. Two fundamental tools are introduced, virtual constraints and hybrid zero dynamics. Virtual constraints are relations on the state variables of a mechanical model that are imposed through a time-invariant feedback controller. One of their roles is to synchronize the robot's joints to an internal gait phasing variable. A second role is to induce a low dimensional system, the zero dynamics, that captures the underactuated aspects of a robot's model, without any approximations. To enhance intuition, the relation between physical constraints and virtual constraints is first established. From here, the hybrid zero dynamics of an underactuated bipedal model is developed, and its fundamental role in the design of asymptotically stable walking motions is established. The chapter includes numerous references to robots on which the highlighted techniques have been implemented.Comment: 17 pages, 4 figures, bookchapte

A new photon recoil experiment: towards a determination of the fine structure constant

We report on progress towards a measurement of the fine structure constant to an accuracy of $5\times 10^{-10}$ or better by measuring the ratio of the Planck constant to the mass of the cesium atom. Compared to similar experiments, ours is improved in three significant ways: (i) simultaneous conjugate interferometers, (ii) multi-photon Bragg diffraction between same internal states, and (iii) an about 1000 fold reduction of laser phase noise to -138 dBc/Hz. Combining that with a new method to simultaneously stabilize the phases of four frequencies, we achieve 0.2 mrad effective phase noise at the location of the atoms. In addition, we use active stabilization to suppress systematic effects due to beam misalignment.Comment: 12 pages, 9 figure

Prevalence and impact of comorbid chronic pain and cigarette smoking among people living with HIV

Rates of chronic pain and cigarette smoking are each substantially higher among people living with HIV (PLWH) than in the general population. The goal of these analyses was to examine the prevalence and impact of comorbid chronic pain and cigarette smoking among PLWH. Participants included 3289 PLWH (83% male) who were recruited from five HIV clinics. As expected, the prevalence of smoking was higher among PLWH with chronic pain (41.9%), than PLWH without chronic pain (26.6%, p <.0001), and the prevalence of chronic pain was higher among current smokers (32.9%), than among former (23.6%) or never (17%) smokers (ps <.0001). PLWH who endorsed comorbid chronic pain and smoking (vs. nonsmokers without chronic pain) were more likely to report cocaine/crack and cannabis use, be prescribed long-term opioid therapy, and have virologic failure, even after controlling for relevant sociodemographic and substance-related variables (ps <.05). These results contribute to a growing empirical literature indicating that chronic pain and cigarette smoking frequently co-occur, and extend this work to a large sample of PLWH. Indeed, PLWH may benefit from interventions that are tailored to address bidirectional pain-smoking effects in the context of HIV

The Role of Oestrogen Receptor Beta (ERβ) in the Aetiology and Treatment of Type 2 Diabetes Mellitus

Introduction: Challenges facing the treatment of type 2 diabetes necessitate the search for agents which act via alternative pathways to provide better therapeutic outcomes. Recently, an increasing body of evidence implicates the activation of oestrogen receptors (ERα and ERβ) in the development and treatment of underlying conditions in type 2 diabetes. This article summarizes available evidence for the involvement of oestrogen receptors in insulin secretion, insulin resistance as well as glucose uptake and highlights the potential of ERβ as a therapeutic target. Background: Recent studies indicate an association between the activation of each of the isoforms of ER and recent findings indicate that ERβ shows promise as a potential target for antidiabetic drugs. In vitro and in vivo studies in receptor knockout mice indicate beneficial actions of selective agonists of ERβ receptor and underscore its therapeutic potential. Conclusion: Studies are needed to further elucidate the exact mechanism underlying the role of ERβ activation as a therapeutic approach in the management of type 2 diabetes

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Marijuana Use Is Not Associated with Changes in Opioid Prescriptions or Pain Severity among People Living with HIV and Chronic Pain

Background:People living with HIV (PLWH) commonly report marijuana use for chronic pain, although there is limited empirical evidence to support its use. There is hope that marijuana may reduce prescription opioid use. Our objective was to investigate whether marijuana use among PLWH who have chronic pain is associated with changes in pain severity and prescribed opioid use (prescribed opioid initiation and discontinuation).Methods:Participants completed self-report measures of chronic pain and marijuana use at an index visit and were followed up for 1 year in the Center for AIDS Research Network of Integrated Clinical Systems (CNICS). Self-reported marijuana use was the exposure variable. Outcome variables were changes in pain and initiation or discontinuation of opioids during the study period. The relationship between exposure and outcomes was assessed using generalized linear models for pain and multivariable binary logistic regression models for opioid initiation/discontinuation.Results:Of 433 PLWH and chronic pain, 28% reported marijuana use in the past 3 months. Median pain severity at the index visit was 6.3/10 (interquartile range 4.7-8.0). Neither increases nor decreases in marijuana use were associated with changes in pain severity, and marijuana use was not associated with either lower odds of opioid initiation or higher odds of opioid discontinuation.Conclusions:We did not find evidence that marijuana use in PLWH is associated with improved pain outcomes or reduced opioid prescribing. This suggests that caution is warranted when counseling PLWH about potential benefits of recreational or medical marijuana

Brief report: The association of chronic pain and long-term opioid therapy with HIV treatment outcomes

Background: Chronic pain occurs in up to 85% of persons living with HIV and is commonly treated with long-term opioid therapy (LTOT). We investigated the impact of chronic pain and LTOT on HIV outcomes. Methods: This was prospective cohort study conducted between July 2015 and July 2016 in 5 HIV primary care clinics. Chronic pain was defined as ≥moderate pain for ≥3 months on the Brief Chronic Pain Questionnaire. Chronic pain and LTOT were assessed at an index visit. Suboptimal retention, defined as at least one "no-show" to primary care, and virologic failure were measured over the subsequent year. Multivariable logistic regression models were built for each outcome adjusting for site. Results: Among 2334 participants, 25% had chronic pain, 27% had suboptimal retention, 12% had virologic failure, and 19% were prescribed LTOT. Among individuals not on LTOT, chronic pain was associated with increased odds of suboptimal retention [adjusted odds ratio (aOR) 1.46, 95% confidence interval (CI): 1.10 to 1.93, P = 0.009] and virologic failure (aOR 1.97, 95% CI: 1.39 to 2.80, P < 0.001). Among individuals with chronic pain, there was no association between LTOT and retention, but LTOT was associated with lower rates of virologic failure (aOR 0.56, 95% CI: 0.33 to 0.96, P = 0.03). Conclusions: Chronic pain in participants not on LTOT was associated with virologic failure. This reinforces the need to identify effective chronic pain treatments for persons living with HIV and investigate their impact on HIV outcomes. The apparent protective association between LTOT and virologic failure in those with pain merits further exploration

No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing.

BACKGROUND: BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction. METHODS: We evaluated a truncating variant, p.Arg798Ter (rs137852986), and 10 missense variants of BRIP1, in 48 144 cases and 43 607 controls of European origin, drawn from 41 studies participating in the Breast Cancer Association Consortium (BCAC). Additionally, we sequenced the coding regions of BRIP1 in 13 213 cases and 5242 controls from the UK, 1313 cases and 1123 controls from three population-based studies as part of the Breast Cancer Family Registry, and 1853 familial cases and 2001 controls from Australia. RESULTS: The rare truncating allele of rs137852986 was observed in 23 cases and 18 controls in Europeans in BCAC (OR 1.09, 95% CI 0.58 to 2.03, p=0.79). Truncating variants were found in the sequencing studies in 34 cases (0.21%) and 19 controls (0.23%) (combined OR 0.90, 95% CI 0.48 to 1.70, p=0.75). CONCLUSIONS: These results suggest that truncating variants in BRIP1, and in particular p.Arg798Ter, are not associated with a substantial increase in breast cancer risk. Such observations have important implications for the reporting of results from breast cancer screening panels.The COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 - HEALTH-F2-2009-223175). BCAC is funded by Cancer Research UK [C1287/A10118, C1287/A12014] and by the European Community´s Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement n° 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 16 CA148065 and 1U19 CA148112 - the GAME-ON initiative), the Department of Defense (W81XWH-10-1- 0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. This study made use of data generated by the Wellcome Trust Case Control consortium. Funding for the project was provided by the Wellcome Trust under award 076113. The results published here are in part based upon data generated by The Cancer Genome Atlas Project established by the National Cancer Institute and National Human Genome Research Institute.This is the author accepted manuscript. The final version is available from BMJ Group at http://dx.doi.org/10.1136/jmedgenet-2015-103529