Valsartan Improves Insulin Sensitivity without Altering Vascular Function in Healthy Overweight Adults without the Metabolic Syndrome

Background. We investigated hyperactivity of the renin-angiotensin system (RAS) as a cause of endothelial dysfunction in obese humans. Methods. Thirty five healthy overweight (BMI = 33.6 ± 6.6 kg m −2) adults (33 ± 10 years old) without cardiovascular risk factors received valsartan (160 mg) orally daily or a matching placebo for 6 weeks each. Results. Baseline flow-mediated dilatation (FMD) and nitroglycerin-mediated dilatation (NMD) were not altered by placebo or valsartan. However, fasting plasma insulin was significantly decreased by valsartan compared to placebo (−4.6 ± 16.0 μUmL−1 versus −0.4 ± 11.6 μUmL−1, P = 0.032) with no changes in glucose. A secondary analysis in patients with elevated waist to hip ratios (ÿ0.85, n = 18) showed an increase in FMD with valsartan. Conclusions. Our findings suggest that angiotensin 2 receptor blockade may aid in the prevention of diabetes even at the earliest stages of risk due solely to uncomplicated obesity. The lack of an improvement in FMD does not support a central role of RAS-hyperactivity in the etiology of the vascular dysfunction due solely to obesity. However, it is possible that obese patients with central adiposity may improve FMD with RAS blockade, and future investigation is warranted in this subgroup.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63259/1/met.2007.0002.pd

Be-10 age constraints on latest Pleistocene and Holocene cirque glaciation across the western United States

Paleoclimate: A rocky reworking of Holocene glaciology New dating of glacially-deposited rocks substantially revises our understanding of the waxing and waning of ice since the last glacial maximum. Glaciologists have long thought that moraines throughout the western United States represent ‘neoglacial’ advances about 6,000 years ago. Now, a multi-institution team led by Shaun Marcott at the University of Wisconsin-Madison has found — using cosmogenic isotopes — that these terminal deposits left by advancing glaciers are instead 9,000 to 15,000 years old. The research advances prior work by using absolute, not relative ages, and documents that glaciers retreated after the last glacial maximum ~ 21,000 years ago, fluctuated locally throughout much of the Holocene, and re-advanced during the Little Ice Age of a few hundred years ago. Glacial advances that might have occurred during the neoglacial were wiped away by the more extensive glaciations of the Little Ice Age

How much do delayed health care seeking, delayed care provision and diversion from primary care contribute to the transmission of STIs

Objectives: To explore the changing pattern of condom use from 1990 to 2000; to identify sociodemographic and behavioural factors associated with condom use; and reasons for condom use in 2000. Methods: Large probability sample surveys administered among those resident in Britain aged 16–44 (n = 13 765 in 1990, n = 11 161 in 2000). Face to face interviews with self completion components collected sociodemographic, behavioural, and attitudinal data. Results: Condom use in the past year among sexually active 16–24 year old men increased from 61.0% in 1990 to 82.1% in 2000 (p<0.0001), and from 42.0% to 63.2% (p<0.0001) among women of the same age, with smaller increases among older age groups. Among individuals reporting at least two partners in the previous 4 week period, approximately two thirds reported inconsistent or no condom use (63.1% (95% CI 55.9% to 69.8%) of the men and 68.5% (95% CI 57.6% to 77.7%) of the women). Conclusions: Rates of condom use increased substantially between 1990 and 2000, particularly among young people. However, inconsistent condom use by individuals with high rates of partner acquisition may contribute significantly to the recent resurgence in STIs. This group is an important target for intensive and specific sexual health interventions

Blood Pressure and Vascular Effects of Leptin in Humans

Background: Leptin may play a role in mediating obesity-related hypertension. However, its effects on the vasculature and blood pressure (BP) remain poorly defined in humans. Methods: In the first study, we performed a short-term, placebo-controlled, randomized, double-blind, cross-over experiment investigating the actions of recombinant human leptin (r-metHuLeptin) in 15 nonobese adults. To compliment the acute study, we retrospectively analyzed available BP results from a previously performed 85–day, placebo-controlled, randomized, double-blind, parallel weight-loss study using r-metHuLeptin in 284 obese adults. Results: In the acute study, conduit artery endothelial function determined by brachial flow-mediated dilatation (FMD) increased 2 hours following 0.2 mg · Kg−1 subcutaneously (SC) of r-metHuLeptin versus placebo (+3.3% versus −2.8%, P = .02). BP remained unchanged 4 hours after injections. In the retrospective analysis of the weight loss study data, 10 mg every day before noon (QAM), 10 mg every day after noon (QPM), or 10 mg twice a day (BID) SC of r-metHuLeptin was found to not alter the degree of weight loss (−3.2 ± 3.7 versus −2.9 ± 3.2 Kg, P = .54), change in systolic (−1.6 + 12.9 versus −2.0 ± 13.9 mmHg, P = .85) and diastolic BP (−0.2 ± 8.7 versus −1.5 ± 8.6, P = .30), as well as heart rate (−1.4 ± 10.7 versus −1.4 ± 10.4 beats/min, P = .98) compared to placebo. Conclusions: In our acute study, marked hyperleptinemia rapidly enhanced endothelial function and did not alter BP. The available data from a longer-term study in healthy obese adults did not demonstrate a significant effect of hyperleptinemia upon BP. These combined findings do not support a direct role for leptin in linking obesity to hypertension, however more studies are required to corroborate these observations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63121/1/met.2006.0023.pd

Impact of pre-enrolment medication use on clinical outcomes in SUMMIT

The impact of prior treatment on results of clinical trials in chronic obstructive pulmonary disease (COPD) has been debated. We used data from the Study to Understand Mortality and Morbidity in COPD Trial to examine the impact of prior treatment on the effects of randomised study drugs on mortality and exacerbations. We used data on 16 417 patients with moderate COPD and heightened cardiovascular risk and information on prior medications to examine the effects of fluticasone furoate (FF), vilanterol (VI) and combined FF/VI compared to placebo on moderate and severe exacerbation as well as mortality. The study was event-driven with a median study exposure of 1.8 years. This study was registered with ClinicalTrials.gov, number NCT01313676. There were no consistent associations between treatment prior to study entry and the effects of FF, VI or FF/VI on exacerbations during the study. However, patients taking inhaled corticosteroids and one or more bronchodilators prior to study entry seemed to have a better effect of active treatments than of placebo on mortality (hazard ratio for FF/VI 0.65, 95% CI 0.48–0.89). Survival in those randomised to placebo was independent of treatment prior to study enrolment. Prior treatment appears to affect treatment effects on mortality but not exacerbations in a randomised controlled trial of patients with COPD and heightened cardiovascular risk

Physical Human Interactive Guidance: Identifying Grasping Principles From Human-Planned Grasps

We present a novel and simple experimental method called Physical Human Interactive Guidance to study human-planned grasping. Instead of studying how the human uses his/her own biological hand or how a human teleoperates a robot hand in a grasping task, the method involves a human interacting physically with a robot arm and hand, carefully moving and guiding the robot into the grasping pose while the robot’s configuration is recorded. Analysis of the grasps from this simple method has produced two interesting results. First, the grasps produced by this method perform better than grasps generated through a state-of-the-art automated grasp planner. Second, this method when combined with a detailed statistical analysis using a variety of grasp measures (physics-based heuristics considered critical for a good grasp) offered insights into how the human grasping method is similar or different from automated grasping synthesis techniques. Specifically, data from the Physical Human Interactive Guidance method showed that the human-planned grasping method provides grasps that are similar to grasps from a state-of-the-art automated grasp planner, but differed in one key aspect. The robot wrists were aligned with the object’s principal axes in the human-planned grasps (termed low skewness in this paper), while the automated grasps used arbitrary wrist orientation. Preliminary tests shows that grasps with low skewness were significantly more robust than grasps with high skewness (77% to 93%). We conclude with a detailed discussion of how the Physical Human Interactive Guidance method relates to existing methods for extracting the human principles for physical interaction.Keywords: Haptic interfaces, Human robot interaction, Manipulators, Grasping, Telerobotic