Generic Medications and Blood Pressure Control in Diabetic Hypertensive Subjects

OBJECTIVE To investigate temporal improvements in blood pressure (BP) control in subjects with diabetes and policy changes regarding generic antihypertensives. RESEARCH DESIGN AND METHODS In a cross-sectional study we used logistic regression models to investigate the temporal relationship between access to generic antihypertensive medications and BP control (<130/80 mmHg) in 5,375 subjects (mean age, 66 ± 9 years; 61% African American) with diabetes and hypertension (HTN) enrolled in the national Results from the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort study between 2003 and 2007. At enrollment, BP was measured and medications in the home determined by medication label review by a trained professional. Generic antihypertensive medication status was ascertained from the U.S. Food and Drug Administration. RESULTS The percentage of subjects accessing generically available antihypertensive medications increased significantly from 66% in 2003 to 81% in 2007 (P < 0.0001), and the odds of achieving a BP <130/80 mmHg in 2007 was 66% higher (odds ratio 1.66 [95% CI 1.30–2.10]) than in 2003. Nevertheless, <50% of participants achieved this goal. African American race, male sex, limited income, and medication nonadherence were significant predictors of inadequate BP control. There was no significant relationship between access to generic antihypertensives and BP control when other demographic factors were included in the model (0.98 [0.96–1.00]). CONCLUSIONS Among African American and white subjects with HTN and diabetes, BP control remained inadequate relative to published guidelines, and racial disparities persisted. Although access to generic antihypertensives increased, this was not independently associated with improved BP control, suggesting that poor BP control is multifactorial

Crack-Like Processes Governing the Onset of Frictional Slip

We perform real-time measurements of the net contact area between two blocks of like material at the onset of frictional slip. We show that the process of interface detachment, which immediately precedes the inception of frictional sliding, is governed by three different types of detachment fronts. These crack-like detachment fronts differ by both their propagation velocities and by the amount of net contact surface reduction caused by their passage. The most rapid fronts propagate at intersonic velocities but generate a negligible reduction in contact area across the interface. Sub-Rayleigh fronts are crack-like modes which propagate at velocities up to the Rayleigh wave speed, VR, and give rise to an approximate 10% reduction in net contact area. The most efficient contact area reduction (~20%) is precipitated by the passage of slow detachment fronts. These fronts propagate at anomalously slow velocities, which are over an order of magnitude lower than VR yet orders of magnitude higher than other characteristic velocity scales such as either slip or loading velocities. Slow fronts are generated, in conjunction with intersonic fronts, by the sudden arrest of sub-Rayleigh fronts. No overall sliding of the interface occurs until either of the slower two fronts traverses the entire interface, and motion at the leading edge of the interface is initiated. Slip at the trailing edge of the interface accompanies the motion of both the slow and sub-Rayleigh fronts. We might expect these modes to be important in both fault nucleation and earthquake dynamics.Comment: 19 page, 5 figures, to appear in International Journal of Fractur

Acute WNT signalling activation perturbs differentiation within the adult stomach and rapidly leads to tumour formation

A role for WNT signalling in gastric carcinogenesis has been suggested due to two major observations. First, patients with germline mutations in adenomatous polyposis coli (APC) are susceptible to stomach polyps and second, in gastric cancer, WNT activation confers a poor prognosis. However, the functional significance of deregulated WNT signalling in gastric homoeostasis and cancer is still unclear. In this study we have addressed this by investigating the immediate effects of WNT signalling activation within the stomach epithelium. We have specifically activated the WNT signalling pathway within the mouse adult gastric epithelium via deletion of either glycogen synthase kinase 3 (GSK3) or APC or via expression of a constitutively active β-catenin protein. WNT pathway deregulation dramatically affects stomach homoeostasis at very short latencies. In the corpus, there is rapid loss of parietal cells with fundic gland polyp (FGP) formation and adenomatous change, which are similar to those observed in familial adenomatous polyposis. In the antrum, adenomas occur from 4 days post-WNT activation. Taken together, these data show a pivotal role for WNT signalling in gastric homoeostasis, FGP formation and adenomagenesis. Loss of the parietal cell population and corresponding FGP formation, an early event in gastric carcinogenesis, as well as antral adenoma formation are immediate effects of nuclear β-catenin translocation and WNT target gene expression. Furthermore, our inducible murine model will permit a better understanding of the molecular changes required to drive tumourigenesis in the stomach

Positive solutions of nonlinear elliptic boundary value problems

This dissertation focuses on the study of positive steady states to classes of nonlinear reaction diffusion (elliptic) systems on bounded domains as well as on exterior domains with Dirichlet boundary conditions. In particular, we study such systems in the challenging case when the reaction terms are negative at the origin, referred in the literature as semipositone problems. For the last 30 years, study of elliptic partial differential equations with semipositone structure has flourished not only for the semilinear case but also for quasilinear case. Here we establish several results that directly contribute to and enhance the literature of semipositone problems. In particular, we discuss existence, non-existence and multiplicity results for classes of superlinear as well as sublinear systems. We establish our results via the method of sub-super solutions, degree theory arguments, a priori bounds and energy analysis

Feasibility of Tomotherapy-Based Image-Guided Radiotherapy for Locally Advanced Oropharyngeal Cancer

PURPOSE: The study aims to assess the feasibility of tomotherapy-based image-guided (IGRT) radiotherapy for locally advanced oropharyngeal cancer. A retrospective review of 33 patients undergoing concurrent chemoradiation for locally advanced oropharyngeal cancers was conducted. Radiotherapy planning, treatment toxicity and loco-regional control were assessed. RESULTS: At a median follow-up of 32 months (6-47 months), no patient developed loco-regional recurrence. Two patients (6%) developed distant metastases. Grade 3-4 acute toxicity was respectively 72% and 25% for mucositis and gastrointestinal toxicity. Two patients (6%) had long-term dependence on tube feedings. Dose-volume histogram demonstrated excellent target volume coverage and low radiation dose to the organs at risk for complications. CONCLUSIONS AND CLINICAL RELEVANCE: IGRT provides excellent loco-regional control but acute toxicity remains significant and needs to be addressed in future prospective trials. The feasibility of Tomotherapy to decrease radiation dose to the normal tissues merits further investigations

Feasibility of image-guided radiotherapy based on helical tomotherapy to reduce contralateral parotid dose in head and neck cancer

Background To evaluate the feasibility of image-guided radiotherapy based on helical Tomotherapy to spare the contralateral parotid gland in head and neck cancer patients with unilateral or no neck node metastases. Methods A retrospective review of 52 patients undergoing radiotherapy for head and neck cancers with image guidance based on daily megavoltage CT imaging with helical tomotherapy was performed. Results Mean contralateral parotid dose and the volume of the contralateral parotid receiving 40 Gy or more were compared between radiotherapy plans with significant constraint (SC) of less than 20 Gy on parotid dose (23 patients) and the conventional constraint (CC) of 26 Gy (29 patients). All patients had PTV coverage of at least 95% to the contralateral elective neck nodes. Mean contralateral parotid dose was, respectively, 14.1 Gy and 24.7 Gy for the SC and CC plans (p < 0.0001). The volume of contralateral parotid receiving 40 Gy or more was respectively 5.3% and 18.2% (p < 0.0001) Conclusion Tomotherapy for head and neck cancer minimized radiotherapy dose to the contralateral parotid gland in patients undergoing elective node irradiation without sacrificing target coverage

Tropospheric jet response to Antarctic ozone depletion: An update with Chemistry-Climate Model Initiative (CCMI) models

The Southern Hemisphere (SH) zonal-mean circulation change in response to Antarctic ozone depletion is re-visited by examining a set of the latest model simulations archived for the Chemistry-Climate Model Initiative (CCMI) project. All models reasonably well reproduce Antarctic ozone depletion in the late 20th century. The related SH-summer circulation changes, such as a poleward intensification of westerly jet and a poleward expansion of the Hadley cell, are also well captured. All experiments exhibit quantitatively the same multi-model mean trend, irrespective of whether the ocean is coupled or prescribed. Results are also quantitatively similar to those derived from the Coupled Model Intercomparison Project phase 5 (CMIP5) high-top model simulations in which the stratospheric ozone is mostly prescribed with monthly- and zonally-averaged values. These results suggest that the ozone-hole-induced SH-summer circulation changes are robust across the models irrespective of the specific chemistry-atmosphere-ocean coupling

Positive solutions for a class of superlinear semipositone systems on exterior domains

2014-2015 UNCG University Libraries Open Access Publishing Fund Grant Winner---see document for abstract

Revising the WHO verbal autopsy instrument to facilitate routine cause-of-death monitoring.

OBJECTIVE: Verbal autopsy (VA) is a systematic approach for determining causes of death (CoD) in populations without routine medical certification. It has mainly been used in research contexts and involved relatively lengthy interviews. Our objective here is to describe the process used to shorten, simplify, and standardise the VA process to make it feasible for application on a larger scale such as in routine civil registration and vital statistics (CRVS) systems. METHODS: A literature review of existing VA instruments was undertaken. The World Health Organization (WHO) then facilitated an international consultation process to review experiences with existing VA instruments, including those from WHO, the Demographic Evaluation of Populations and their Health in Developing Countries (INDEPTH) Network, InterVA, and the Population Health Metrics Research Consortium (PHMRC). In an expert meeting, consideration was given to formulating a workable VA CoD list [with mapping to the International Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) CoD] and to the viability and utility of existing VA interview questions, with a view to undertaking systematic simplification. FINDINGS: A revised VA CoD list was compiled enabling mapping of all ICD-10 CoD onto 62 VA cause categories, chosen on the grounds of public health significance as well as potential for ascertainment from VA. A set of 221 indicators for inclusion in the revised VA instrument was developed on the basis of accumulated experience, with appropriate skip patterns for various population sub-groups. The duration of a VA interview was reduced by about 40% with this new approach. CONCLUSIONS: The revised VA instrument resulting from this consultation process is presented here as a means of making it available for widespread use and evaluation. It is envisaged that this will be used in conjunction with automated models for assigning CoD from VA data, rather than involving physicians

Constant light enhances synchrony among circadian clock cells and promotes behavioral rhythms in VPAC(2)-signaling deficient mice

Individual neurons in the suprachiasmatic nuclei (SCN) contain an intracellular molecular clock and use intercellular signaling to synchronize their timekeeping activities so that the SCN can coordinate brain physiology and behavior. The neuropeptide vasoactive intestinal polypeptide (VIP) and its VPAC2 receptor form a key component of intercellular signaling systems in the SCN and critically control cellular coupling. Targeted mutations in either the intracellular clock or intercellular neuropeptide signaling mechanisms, such as VIP-VPAC2 signaling, can lead to desynchronization of SCN neuronal clocks and loss of behavioral rhythms. An important goal in chronobiology is to develop interventions to correct deficiencies in circadian timekeeping. Here we show that extended exposure to constant light promotes synchrony among SCN clock cells and the expression of ~24 h rhythms in behavior in mice in which intercellular signaling is disrupted through loss of VIP-VPAC2 signaling. This study highlights the importance of SCN synchrony for the expression of rhythms in behavior and reveals how non-invasive manipulations in the external environment can be used to overcome neurochemical communication deficits in this important brain system