CHEETAH: Circuit-Switched High-Speed End-to-End Transport Architecture Testbed

We propose a circuit-switched high-speed end-to-end transport architecture (CHEETAH) as a networking solution to provide high-speed end-to-end circuit connectivity to end hosts on a dynamic call-by-call basis. Not only is it envisioned as a complementary service to the basic connectionless service provided by today’s Internet; it also relies on and leverages the presence of this service. Noting the dominance of Ethernet in LANs and SONET/SDH in WANs, CHEETAH circuits will consist of Ethernet segments at the ends and Ethernet-over-SONET segments in the wide area. In this article we explain the CHEETAH concept and describe a wide-area experimental network testbed we have deployed based on this concept. The network testbed currently extends between Raleigh, North Carolina, Atlanta, Georgia, and Oak Ridge, Tennessee, and uses off-the-shelf switches. We have created CHEETAH software to run on end hosts to enable automated use of this network by applications. Our first users of this network testbed and software will be the Terascale Supernova Initiative (TSI) project researchers, who plan to use this network for large file transfers and remote visualizations

Topiramate and metformin are effective add-on treatments in controlling antipsychotic-induced weight gain:a systematic review and network meta-analysis

Background: Antipsychotic drugs may lead to side effects such as obesity, diabetes, dyslipidemia, and cardiovascular disease. The current systematic review and network meta-analysis analyzes and provides an update on the clinical performance of these add-ons in comparison to placebo on body weight and body mass index (BMI) reductions.Methods: A comprehensive literature search was performed on electronic databases: PubMed (1946-), Embase (1974-), Cochrane library (1992-), and OpenGrey (2000-) until 31 July 2018. Network meta-analyses, comparing the body weight change, BMI change and withdrawn due to adverse events of different pharmacological add-ons, was performed using a multivariate meta-regression model with random-effects, adopting a frequentist approach. To rank the prognosis for all add-ons, we used surface under the cumulative ranking (SUCRA) values.Outcomes: From 614 potential studies identified, 27 eligible studies (n = 1,349 subjects) were included. All the studies demonstrated low to moderate risk of bias. For the analysis of body weight change, all add-ons except Ranitidine showed significant weight reductions comparing to placebo. The effectiveness rank based on SUCRA results from highest to lowest was Sibutramine, Topiramate, Metformin, Reboxetine, Ranitidine, and placebo. A similar pattern was seen for BMI change. The analysis of safety outcome did not detect significantly increased withdrawn number from the add-ons. Current evidence showed relatively good tolerance and safety of using the pharmacological add-ons.Interpretation: Topiramate and Metformin are effective add-on treatments in controlling antipsychotic-induced weight gain, comparing to placebo. They are well tolerated in short-term period. Although Sibutramine has the highest rank of the effectiveness, its license has been withdrawn in many countries due to its adverse effects. Hence, Sibutramine should not be adopted to treat antipsychotic-induced weight gain.</p

Validation of "Care of the Dying Evaluation" in Emergency Medicine (CODE-EM): pilot phase of end-of-life management protocol offered within emergency room (EMPOWER) study.

BackgroundAn increasing number of patients who present to emergency departments are at their end-of-life phase and have significant palliative care needs such as in symptom control for pain and dyspnoea. Evaluating quality of care provided is imperative, yet there is no suitable tool validated in the emergency and Asian settings. We aim to examine the face and construct validity, and reliability of a newly developed questionnaire, Care of the Dying Evaluation - Emergency Medicine, for measuring the quality of end-of-life care in an Asian emergency context.MethodsA mixed methods pilot study was conducted. Participants composed of the next-of-kin to thirty dying patients who presented to the emergency departments of three public hospitals in Singapore. Qualitative evaluation, using cognitive "think-aloud" interviews, and quantitative analysis were employed. Percentage agreement and κ statistic were measured to evaluate temporal stability of the questionnaire. Cronbach's α and item-total correlations were used to assess internal consistency within the constructs. Confirmatory factor analysis was performed for construct validity.ResultsAll participants reported clear understanding of the questionnaire with no ambiguity; a minority felt the questions caused emotional distress (7/30, 23.3%). The questions showed moderate to good test-retest reliability. Internal consistencies within the constructs were good for "ENVIRONMENT" and "CARE", and moderate for "COMMUNICATION". Factor loadings range from 0.40 to 0.99.ConclusionsThe Care of the Dying Evaluation - Emergency Medicine questionnaire may be valid and reliable for use in an Asian emergency setting. Our prospective multicentre study using this evaluation tool may provide more insight on the quality of care rendered to dying patients and identify areas for improvement.Trial registrationClinicalTrials.gov (NCT03906747)

Topiramate and Metformin Are Effective Add-On Treatments in Controlling Antipsychotic-Induced Weight Gain: A Systematic Review and Network Meta-Analysis

Background: Antipsychotic drugs may lead to side effects such as obesity, diabetes, dyslipidemia, and cardiovascular disease. The current systematic review and network meta-analysis analyzes and provides an update on the clinical performance of these add-ons in comparison to placebo on body weight and body mass index (BMI) reductions.Methods: A comprehensive literature search was performed on electronic databases: PubMed (1946-), Embase (1974-), Cochrane library (1992-), and OpenGrey (2000-) until 31 July 2018. Network meta-analyses, comparing the body weight change, BMI change and withdrawn due to adverse events of different pharmacological add-ons, was performed using a multivariate meta-regression model with random-effects, adopting a frequentist approach. To rank the prognosis for all add-ons, we used surface under the cumulative ranking (SUCRA) values.Outcomes: From 614 potential studies identified, 27 eligible studies (n = 1,349 subjects) were included. All the studies demonstrated low to moderate risk of bias. For the analysis of body weight change, all add-ons except Ranitidine showed significant weight reductions comparing to placebo. The effectiveness rank based on SUCRA results from highest to lowest was Sibutramine, Topiramate, Metformin, Reboxetine, Ranitidine, and placebo. A similar pattern was seen for BMI change. The analysis of safety outcome did not detect significantly increased withdrawn number from the add-ons. Current evidence showed relatively good tolerance and safety of using the pharmacological add-ons.Interpretation: Topiramate and Metformin are effective add-on treatments in controlling antipsychotic-induced weight gain, comparing to placebo. They are well tolerated in short-term period. Although Sibutramine has the highest rank of the effectiveness, its license has been withdrawn in many countries due to its adverse effects. Hence, Sibutramine should not be adopted to treat antipsychotic-induced weight gain

Sacubitril/valsartan versus valsartan in regressing myocardial fibrosis in hypertension: a prospective, randomized, open-label, blinded endpoint clinical trial protocol

BackgroundDiffuse interstitial myocardial fibrosis is a key common pathological manifestation in hypertensive heart disease (HHD) progressing to heart failure (HF). Angiotensin receptor–neprilysin inhibitors (ARNi), now a front-line treatment for HF, confer benefits independent of blood pressure, signifying a multifactorial mode of action beyond hemodynamic regulation. We aim to test the hypothesis that compared with angiotensin II receptor blockade (ARB) alone, ARNi is more effective in regressing diffuse interstitial myocardial fibrosis in HHD.MethodsRole of ARNi in Ventricular Remodeling in Hypertensive LVH (REVERSE-LVH) is a prospective, randomized, open-label, blinded endpoint (PROBE) clinical trial. Adults with hypertension and left ventricular hypertrophy (LVH) according to Asian sex- and age-specific thresholds on cardiovascular magnetic resonance (CMR) imaging are randomized to treatment with either sacubitril/valsartan (an ARNi) or valsartan (an ARB) in 1:1 ratio for a duration of 52 weeks, at the end of which a repeat CMR is performed to assess differential changes from baseline between the two groups. The primary endpoint is the change in CMR-derived diffuse interstitial fibrosis volume. Secondary endpoints include changes in CMR-derived left ventricular mass, volumes, and functional parameters. Serum samples are collected and stored to assess the effects of ARNi, compared with ARB, on circulating biomarkers of cardiac remodeling. The endpoints will be analyzed with reference to the corresponding baseline parameters to evaluate the therapeutic effect of sacubitril/valsartan vs. valsartan.DiscussionREVERSE-LVH will examine the anti-fibrotic potential of sacubitril/valsartan and will offer mechanistic insights into the clinical benefits of sacubitril/valsartan in hypertension in relation to cardiac remodeling. Advancing the knowledge of the pathophysiology of HHD will consolidate effective risk stratification and personalized treatment through a multimodal manner integrating complementary CMR and biomarkers into the conventional care approach.Clinical Trial Registration: ClinicalTrials.gov, identifier, NCT03553810

Spatio-temporal modelling of particulate matter and its application to assessing mortality effects of long-term exposure

abstractPublic HealthMasterMaster of Philosoph

Diagnostic yield of ambulatory oesophageal studies on versus off proton pump inhibitors: a systematic review and meta-analysis

Background: Patients with persistent gastroesophageal reflux disease symptoms despite proton pump inhibitors are increasingly encountered. It remains controversial if proton pump inhibitors should be stopped before functional oesophageal tests. Aim: This meta-analysis compares the positive yield of oesophageal studies performed off versus on proton pump inhibitors. Methods: Pubmed, Embase and the Cochrane Library were searched for eligible studies. Outcomes assessed were the number of subjects with: elevated oesophageal acid exposure time when studied off versus on proton pump inhibitors; positive symptom index (≥50%) and/or positive symptom association probability (≥95%) for acid reflux; and/or non-acid reflux events off versus on proton pump inhibitors. The random effects model was applied. Results: Fifteen studies (n = 5033 individuals; 33% on proton pump inhibitors; 32% men; mean age 52.1 years) were analysed. Pooled risk ratio for the comparison of high oesophageal acid exposure time off versus on proton pump inhibitors was 2.16 (95% confidence interval (CI) 1.42-3.28). The risk ratio of a positive symptom index (acid reflux) was 2.64 (95% CI 1.52-4.57) and the risk ratio of a positive symptom association probability (acid reflux) was 2.94 (95% CI 2.31-3.74). Conversely, the risk ratio of a positive symptom index (non-acid reflux) was 0.96 (95% CI 0.49-1.88) and risk ratio of a positive symptom association probability (non-acid reflux) was 0.54 (95% CI 0.30-0.99). Conclusions: Oesophageal studies after proton pump inhibitor cessation improve the positive yield for acid reflux-related events but reduce the detection of symptomatic non-acid reflux events.status: publishe

Regular Exercise Enhances the Immune Response Against Microbial Antigens Through Up-Regulation of Toll-like Receptor Signaling Pathways

Background/Aims: Regular physical exercise can enhance resistance to many microbial infections. However, little is known about the mechanism underlying the changes in the immune system induced by regular exercise. Methods: We recruited members of a university badminton club as the regular exercise (RE) group and healthy sedentary students as the sedentary control (SC) group. We investigated the distribution of peripheral blood mononuclear cell (PBMC) subsets and functions in the two groups. Results: There were no significant differences in plasma cytokine levels between the RE and SC groups in the true resting state. However, enhanced levels of IFN-&#947;, TNF-α, IL-6, IFN-α and IL-12 were secreted by PBMCs in the RE group following microbial antigen stimulation, when compared to the SC group. In contrast, the levels of TNF-α and IL-6 secreted by PBMC in the RE group were suppressed compared with those in SC group following non-microbial antigen stimulation (concanavalin A or α-galactosylceramide). Furthermore, PBMC expression of TLR2, TLR7 and MyD88 was significantly increased in the RE group in response to microbial antigen stimulation. Conclusion: Regular exercise enhances immune cell activation in response to pathogenic stimulation leading to enhanced cytokine production mediated via the TLR signaling pathways