Patient-Reported Barriers to Adherence Among ACEI/ARB Users from a Motivational Interviewing Telephonic Intervention

Purpose: Hypertension is a common comorbidity among type 2 diabetes mellitus (T2DM) patients, which increases the risk of cardiovascular diseases. Despite the proven benefit of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in this population, poor medication adherence is prevalent, resulting in higher complications and mortality rate. Motivational interviewing (MoI) has demonstrated effectiveness in improving medication adherence and identifying barriers. This study aimed to assess and identify patient-reported barriers to adherence to ACEI/ARB from an MoI telephonic intervention conducted by student pharmacist interns. Patients and Methods: This retrospective study was conducted within an MoI intervention customized by past ACEI/ARB adherence trajectories for nonadherent patients with T2DM and hypertension enrolled in a Medicare Advantage Plan. Adherence barriers were extracted from the interviewers’ notes by two independent researchers. Descriptive analysis was performed to summarize the overall frequency of barriers as well as across trajectory groups, identified from the initial and follow-up calls. Results: In total, 247 patients received the initial MoI call from which 41% did not communicate any barrier for ACEI/ARB use despite having low adherence. About 59% of the patients reported at least one barrier during the initial call. The most common barriers included forgetfulness, discontinuation by physicians, side effects, multiple comorbidities, polypharmacy, lack of knowledge about disease/medication, and cost issues. The follow-up calls helped with uncovering at least one new barrier for 28 patients who previously communicated a different issue with their medication during the first call. Additionally, 18 patients with initial denial for having any barrier to adherence reported at least one barrier throughout the follow-up calls. Conclusion: This study summarized patient-reported barriers to ACEI/ARB adherence from an MoI telephonic intervention performed among nonadherent patients. Identifying specific barriers for patients may help to further design tailored interventions that address the barriers and improve adherence

The Massive Progenitor of the Possible Type II-Linear Supernova 2009hd in Messier 66

We present observations of SN2009hd in the nearby galaxy M66. This SN is one of the closest to us in recent years but heavily obscured by dust, rendering it unusually faint in the optical, given its proximity. We find that the observed properties of SN2009hd support its classification as a possible Type II-L SN, a relatively rare subclass of CC-SNe. High-precision relative astrometry has been employed to attempt to identify a SN progenitor candidate, based on a pixel-by-pixel comparison between HST F555W and F814W images of the SN site prior to explosion and at late times. A progenitor candidate is identified in the F814W images only; this object is undetected in F555W. Significant uncertainty exists in the astrometry, such that we cannot definitively identify this object as the SN progenitor. Via insertion of artificial stars into the pre-SN HST images, we are able to constrain the progenitor's properties to those of a possible supergiant, with M(F555W)0>-7.6 mag and (V-I) 0>0.99 mag. The magnitude and color limits are consistent with a luminous RSG; however, they also allow for the possibility that the star could have been more yellow than red. From a comparison with theoretical massive-star evolutionary tracks, which include rotation and pulsationally enhanced mass loss, we can place a conservative upper limit on the initial mass for the progenitor of <20 M_sun. If the actual mass of the progenitor is near the upper range allowed by our derived mass limit, then it would be consistent with that for the identified progenitors of the SNII-L 2009kr and the high-luminosity SNII-P 2008cn. The progenitors of these three SNe may possibly bridge the gap between lower-mass RSG that explode as SNeII-P and LBV, or more extreme RSG, from which the more exotic SNeII-n may arise. Very late-time imaging of the SN2009hd site may provide us with more clues regarding the true nature of its progenitor.Comment: 19 pages, 9 figures, 3 tables, accepted for publication in Ap

Immunogenicity and Efficacy of Single Antigen Gp63, Polytope and PolytopeHSP70 DNA Vaccines against Visceral Leishmaniasis in Experimental Mouse Model

Polytope approach of genetic immunization is a promising strategy for the prevention of infectious disease as it is capable of generating effective cell mediated immunity by delivering the T cell epitopes assembled in series. Leishmaniasis is a significant world wide health problem for which no vaccine exists. In this study we have compared immunogenicity and efficacy of three types of DNA vaccines: single antigen Gp63 (Gp63/pcDNA), polytope (Poly/pcDNA) and Polytope fused with hsp70 (Poly/hsp/pcDNA) against visceral leishmaniasis in susceptible BALB/c mice. Mice vaccinated with these plasmids generated strong Th1 immune response as seen by dominating IFN-γ over IL-10 cytokine. Interestingly, cytotoxic responses generated by polytope DNA plasmid fused with hsp70 of Leishmania donovani were significantly higher when compared to polytope and single antigen Gp63 vaccine. Challenge studies revealed that the parasite load in liver and spleen was significantly lower with Poly/hsp/pcDNA vaccination compared to other vaccines. Therefore, our study indicates that polytope DNA vaccine is a feasible, practical and effective approach for visceral leishmaniasis

(Re) Locating community in relationships: questions for public policy

This is the author accepted manuscript. The final version is available from SAGE Publications via the DOI in this record.This paper argues that we should think of community as being about social relationships rather than a ‘thing’ that is ‘lost’, ‘found’ or ‘made’. The paper draws on the philosophy of Roberto Esposito and the sociology of David Studdert to highlight the overlaps in their approaches to community. Both argue that community is ontological, as unavoidably ‘with us’. The paper then draws upon two empirical examples to argue that this approach could enable a different kind of public policy in relation to community. Policy would focus on existing relationships as the starting point for any efforts to effect social change. The implications for contemporary debates about localism are explored at the end of the paper.I am very grateful to David Studdert and Valerie Walkerdine for inviting me to the workshop on community and localism held at Cardiff University in April 2014 that stimulated this special issue of Sociological Review. I am also very grateful to the Leverhulme Trust for the research funding and to Nick Coke, Tessy Britton and Laura Billings for their invaluable contributions to the arguments made. The comments from three referees, the editors and Patrick Devine-Wright were extremely helpful in improving the paper

Extensive Genetic Diversity, Unique Population Structure and Evidence of Genetic Exchange in the Sexually Transmitted Parasite Trichomonas vaginalis

The human parasite Trichomonas vaginalis causes trichomoniasis, the world's most common non-viral sexually transmitted infection. Research on T. vaginalis genetic diversity has been limited by a lack of appropriate genotyping tools. To address this problem, we recently published a panel of T. vaginalis-specific genetic markers; here we use these markers to genotype isolates collected from ten regions around the globe. We detect high levels of genetic diversity, infer a two-type population structure, identify clinically relevant differences between the two types, and uncover evidence of genetic exchange in what was believed to be a clonal organism. Together, these results greatly improve our understanding of the population genetics of T. vaginalis and provide insights into the possibility of genetic exchange in the parasite, with implications for the epidemiology and control of the disease. By taking into account the existence of different types and their unique characteristics, we can improve understanding of the wide range of symptoms that patients manifest and better implement appropriate drug treatment. In addition, by recognizing the possibility of genetic exchange, we are more equipped to address the growing concern of drug resistance and the mechanisms by which it may spread within parasite populations

Search of the Orion spur for continuous gravitational waves using a loosely coherent algorithm on data from LIGO interferometers

We report results of a wideband search for periodic gravitational waves from isolated neutron stars within the Orion spur towards both the inner and outer regions of our Galaxy. As gravitational waves interact very weakly with matter, the search is unimpeded by dust and concentrations of stars. One search disk (A) is 6.87° in diameter and centered on 20h10m54.71s+33°33′25.29′′, and the other (B) is 7.45° in diameter and centered on 8h35m20.61s-46°49′25.151′′. We explored the frequency range of 50-1500 Hz and frequency derivative from 0 to -5×10-9 Hz/s. A multistage, loosely coherent search program allowed probing more deeply than before in these two regions, while increasing coherence length with every stage. Rigorous follow-up parameters have winnowed the initial coincidence set to only 70 candidates, to be examined manually. None of those 70 candidates proved to be consistent with an isolated gravitational-wave emitter, and 95% confidence level upper limits were placed on continuous-wave strain amplitudes. Near 169 Hz we achieve our lowest 95% C.L. upper limit on the worst-case linearly polarized strain amplitude h0 of 6.3×10-25, while at the high end of our frequency range we achieve a worst-case upper limit of 3.4×10-24 for all polarizations and sky locations. © 2016 American Physical Society

Genomic correlates of glatiramer acetate adverse cardiovascular effects lead to a novel locus mediating coronary risk

Glatiramer acetate is used therapeutically in multiple sclerosis but also known for adverse effects including elevated coronary artery disease (CAD) risk. The mechanisms underlying the cardiovascular side effects of the medication are unclear. Here, we made use of the chromosomal variation in the genes that are known to be affected by glatiramer treatment. Focusing on genes and gene products reported by drug-gene interaction database to interact with glatiramer acetate we explored a large meta-analysis on CAD genome-wide association studies aiming firstly, to investigate whether variants in these genes also affect cardiovascular risk and secondly, to identify new CAD risk genes. We traced association signals in a 200-kb region around genomic positions of genes interacting with glatiramer in up to 60 801 CAD cases and 123 504 controls. We validated the identified association in additional 21 934 CAD cases and 76 087 controls. We identified three new CAD risk alleles within the TGFB1 region on chromosome 19 that independently affect CAD risk. The lead SNP rs12459996 was genome-wide significantly associated with CAD in the extended meta-analysis (odds ratio 1.09, p = 1.58×10-12). The other two SNPs at the locus were not in linkage disequilibrium with the lead SNP and by a conditional analysis showed p-values of 4.05 × 10-10 and 2.21 × 10-6. Thus, studying genes reported to interact with glatiramer acetate we identified genetic variants that concordantly with the drug increase the risk of CAD. Of these, TGFB1 displayed signal for association. Indeed, the gene has been associated with CAD previously in both in vivo and in vitro studies. Here we establish genome-wide significant association with CAD in large human samples.This work was supported by grants from the Fondation Leducq (CADgenomics: Understanding CAD Genes, 12CVD02), the German Federal Ministry of Education and Research (BMBF) within the framework of the e:Med research and funding concept (e:AtheroSysMed, grant 01ZX1313A-2014 and SysInflame, grant 01ZX1306A), and the European Union Seventh Framework Programme FP7/2007-2013 under grant agreement no HEALTH-F2-2013-601456 (CVgenes-at-target). Further grants were received from the DFG as part of the Sonderforschungsbereich CRC 1123 (B2). T.K. was supported by a DZHK Rotation Grant. I.B. was supported by the Deutsche Forschungsgemeinschaft (DFG) cluster of excellence ‘Inflammation at Interfaces’. F.W.A. is supported by a Dekker scholarship-Junior Staff Member 2014T001 - Netherlands Heart Foundation and UCL Hospitals NIHR Biomedical Research Centre

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis