Exploring and understanding the scope and value of the Parkinson’s nurse in the UK (The USP Project): a realist economic evaluation protocol

Introduction There are multiple configurations of specialist nurses working in the field of Parkinson’s. Parkinson’s Nurse Specialists (PNSs) are recognised as playing a pivotal role; however, there is little published evidence to demonstrate their effectiveness. Further evidence is needed to establish which aspects of the PNSs provide the greatest benefit to people with Parkinson’s and their families, and the cost-effectiveness of different models of care. Methods and analysis Realist approaches explain how and why programmes work (or not) through striving to answer the question: what works, for whom and under what circumstances. This research uses a realist evaluation and aims to integrate an economic analysis within the realist framework. We refer to this as ‘realist economic evaluation’. It comprises four phases: (1) developing resource-sensitive initial programme theories (IPTs) using surveys to gain a better understanding of the role and impact (costs and benefits) of the PNSs; (2) testing the IPTs through qualitative interviews and quantitative data analysis; (3) evaluating the cost and resource use implications alongside the benefits associated with the role of the PNSs and (4) iteratively refining the IPTs throughout the project. The IPTs will draw on both quantitative and qualitative data. The result of the study will be a series of refined programme theories, which will explain how specialist nurses work in the field of Parkinson’s in the UK, what impact they have on people with Parkinson’s and their families and carers, and at what cost. Ethics and dissemination Northumbria University, the Health Research Authority and Health and Care Research Wales have approved this study. Key findings will be disseminated throughout the duration of the project online and through social media, and via annual and regional Parkinson’s meetings and the Parkinson’s UK Excellence Network. Academic dissemination will occur through publication and conference presentations

Leveraging Geospatial Information to address Space Epidemiology through Multi\unicode{x2013}omics \unicode{x2013} Report of an Interdisciplinary Workshop

This article will summarize the workshop proceedings of a workshop conducted at the University of Missouri that addressed the use of multi-omics fused with geospatial information to assess and improve the precision and environmental analysis of indicators of crew space health. The workshop addressed the state of the art of multi-omics research and practice and the potential future use of multi-omics platforms in extreme environments. The workshop also focused on potential new strategies for data collection, analysis, and fusion with crosstalk with the field of environmental health, biosecurity, and radiation safety, addressing gaps and shortfalls and potential new approaches to enhancing astronaut health safety and security. Ultimately, the panel proceedings resulted in a synthesis of new research and translational opportunities to improve space and terrestrial epidemiology. In the future, early disease prevention that employs new and expanded data sources enhanced by the analytic precision of geospatial information and artificial intelligence algorithms.Comment: 9 pages, 1 figur

Religious Identity, Religious Attendance, and Parental Control

Using a national sample of adolescents aged 10–18 years and their parents (N = 5,117), this article examines whether parental religious identity and religious participation are associated with the ways in which parents control their children. We hypothesize that both religious orthodoxy and weekly religious attendance are related to heightened levels of three elements of parental control: monitoring activities, normative regulations, and network closure. Results indicate that an orthodox religious identity for Catholic and Protestant parents and higher levels of religious attendance for parents as a whole are associated with increases in monitoring activities and normative regulations of American adolescents

Pharmacological characterisation of MDI-222, a novel AMPA receptor positive allosteric modulator with an improved safety profile

There is considerable interest in positive allosteric modulators (PAMs) of the α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) subtype of ionotropic glutamate receptors as therapeutic agents for a range of cognitive and mood disorders. However, the challenge is to increase AMPA receptor (AMPAR) function sufficient to enhance cognitive function but not to the extent that there are mechanism-related pro-convulsant or convulsant side effects. In this present study, we report the preclinical pharmacology data for MDI-222, an AMPAR PAM which enhances cognition but has a much reduced side-effect (i.e. convulsant) liability relative to other molecules of this mechanism

Cervical artery dissection in patients >= 60 years Often painless, few mechanical triggers

Objective: In a cohort of patients diagnosed with cervical artery dissection (CeAD), to determine the proportion of patients aged >= 60 years and compare the frequency of characteristics (presenting symptoms, risk factors, and outcome) in patients aged = 60 years. Methods: We combined data from 3 large cohorts of consecutive patients diagnosed with CeAD (i. e., Cervical Artery Dissection and Ischemic Stroke Patients-Plus consortium). We dichotomized cases into 2 groups, age >= 60 and Results: Among 2,391 patients diagnosed with CeAD, we identified 177 patients (7.4%) aged >= 60 years. In this age group, cervical pain (ORadjusted 0.47 [0.33-0.66]), headache (ORadjusted 0.58 [0.42-0.79]), mechanical trigger events (ORadjusted 0.53 [0.36-0.77]), and migraine (ORadjusted 0.58 [0.39-0.85]) were less frequent than in younger patients. In turn, hypercholesterolemia (ORadjusted 1.52 [1.1-2.10]) and hypertension (ORadjusted 3.08 [2.25-4.22]) were more frequent in older patients. Key differences between age groups were confirmed in secondary analyses. In multivariable, adjusted analyses, favorable outcome (i. e., modified Rankin Scale score 0-2) was less frequent in the older age group (ORadjusted 0.45 [0.25, 0.83]). Conclusion: In our study population of patients diagnosed with CeAD, 1 in 14 was aged >= 60 years. In these patients, pain and mechanical triggers might be missing, rendering the diagnosis more challenging and increasing the risk ofmissed CeAD diagnosis in older patients.Peer reviewe

Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke

Genetic factors have been implicated in stroke risk but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) in ischemic stroke and its subtypes in 3,548 cases and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 cases and 6,281 controls. We replicated reported associations between variants close to PITX2 and ZFHX3 with cardioembolic stroke, and a 9p21 locus with large vessel stroke. We identified a novel association for a SNP within the histone deacetylase 9(HDAC9) gene on chromosome 7p21.1 which was associated with large vessel stroke including additional replication in a further 735 cases and 28583 controls (rs11984041, combined P = 1.87×10−11, OR=1.42 (95% CI) 1.28-1.57). All four loci exhibit evidence for heterogeneity of effect across the stroke subtypes, with some, and possibly all, affecting risk for only one subtype. This suggests differing genetic architectures for different stroke subtypes

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Biologically Important Areas II for cetaceans within U.S. and adjacent waters – Hawaiʻi Region

In this assessment we incorporated published and unpublished information to delineate and score Biologically Important Areas (BIAs) for cetaceans in the Hawaiʻi region following standardized criteria. Twenty-six cetacean species have been documented in Hawaiʻi. Eleven odontocete species have distinct small populations resident to one or more island areas: rough-toothed dolphins, pantropical spotted dolphins, common bottlenose dolphins, spinner dolphins, short-finned pilot whales, false killer whales, pygmy killer whales, melon-headed whales, Blainville’s beaked whales, Cuvier’s beaked whales, and dwarf sperm whales. Eight species of mysticetes have been documented, although their occurrence and behavior are poorly understood, with the exception of breeding humpback whales and, more recently, common minke whales. Thirty-five BIAs were delineated or revised from the initial 2015 effort: 33 for small and resident odontocete populations and two for humpback whale reproductive areas. Hierarchical BIAs reflecting core areas of use or population-specific ranges were delineated for nine species. Reproductive watch list areas were designated for common minke whales in the main Hawaiian Islands (MHI) and humpback whales in the Northwestern Hawaiian Islands (NWHI); these areas did not meet the criteria for a BIA due to limited supporting information. All but three BIAs were in the MHI, reflecting the disparities in research effort between this region and the NWHI. Spatial extents of BIA boundaries ranged from 457 km2 to 138,001 km2 (median = 8,299 km2). Scores (range: 1-3) for Data Support and Boundary Certainty were moderate to high (mean = 2.40 and 2.43, respectively), while Intensity and Importance scores were slightly lower (mean = 1.94 and 1.89, respectively). Many of the Hawaiʻi species have been extensively studied over several decades; accordingly, this region ranks among the highest in terms of Data Support relative to other regions. BIAs presented here describe known ranges of small resident populations, intensities of use, and uncertainties in important areas for cetaceans in Hawaiʻi based on the best available data, and have also revealed knowledge gaps to guide future research efforts

Lifetime history of indoor tanning in young people: a retrospective assessment of initiation, persistence, and correlates

<p>Abstract</p> <p>Background</p> <p>Despite educational and public health campaigns to convey the risks of indoor tanning, many individuals around the world continue to engage in this behavior. Few descriptive studies of indoor tanning have collected information pertaining to the lifetime history of indoor tanning, thereby limiting our ability to understand indoor tanning patterns and potentially target interventions for individuals who not only initiate, but continue to persistently engage in indoor tanning.</p> <p>Methods</p> <p>In-person interviews elicited detailed retrospective information on lifetime history of indoor tanning among white individuals (n = 401) under age 40 seen by a dermatologist for a minor benign skin condition. These individuals were controls in a case-control study of early-onset basal cell carcinoma. Outcomes of interest included ever indoor tanning in both males and females, as well as persistent indoor tanning in females - defined as females over age 31 who tanned indoors at least once in the last three or all four of four specified age periods (ages 11-15, 16-20, 21-30 and 31 or older). Multivariate logistic regression was used to identify sociodemographic and lifestyle correlates of ever and persistent indoor tanning in females.</p> <p>Results</p> <p>Approximately three-quarters (73.3%) of females and 38.3% of males ever tanned indoors, with a median age of initiation of 17.0 and 21.5, respectively. Among indoor tanners, 39.3% of females and 21.7% of males reported being burned while indoor tanning. Female ever indoor tanners were younger, had darker color eyes, and sunbathed more frequently than females who never tanned indoors. Using unique lifetime exposure data, 24.7% of female indoor tanners 31 and older persistently tanned indoors starting as teenagers. Female persistent indoor tanners drank significantly more alcohol, were less educated, had skin that tanned with prolonged sun exposure, and sunbathed outdoors more frequently than non-persistent tanners.</p> <p>Conclusions</p> <p>Indoor tanning was strikingly common in this population, especially among females. Persistent indoor tanners had other high-risk behaviors (alcohol, sunbathing), suggesting that multi-faceted behavioral interventions aimed at health promotion/disease prevention may be needed in this population.</p

Genetics of the thrombomodulin-endothelial cell protein C receptor system and the risk of early-onset ischemic stroke

Background and purpose Polymorphisms in coagulation genes have been associated with early-onset ischemic stroke. Here we pursue an a priori hypothesis that genetic variation in the endothelial-based receptors of the thrombomodulin-protein C system (THBD and PROCR) may similarly be associated with early-onset ischemic stroke. We explored this hypothesis utilizing a multi-tage design of discovery and replication. Methods Discovery was performed in the Genetics-of-Early-Onset Stroke (GEOS) Study, a biracial population-based case-control study of ischemic stroke among men and women aged 1549 including 829 cases of first ischemic stroke (42.2% African-American) and 850 age-comparable stroke-free controls (38.1% African-American). Twenty-four single-nucleotide-polymorphisms (SNPs) in THBD and 22 SNPs in PROCR were evaluated. Following LD pruning (r(2)>= 0.8), we advanced uncorrelated SNPs forward for association analyses. Associated SNPs were evaluated for replication in an early-onset ischemic stroke population (onset-ge Results Among GEOS Caucasians, PROCR rs9574, which was in strong LD with 8 other SNPs, and one additional independent SNP rs2069951, were significantly associated with ischemic stroke (rs9574, OR = 1.33, p = 0.003; rs2069951, OR = 1.80, p = 0.006) using an additive-model adjusting for age, gender and population-structure. Adjusting for risk factors did not change the associations; however, associations were strengthened among those without risk factors. PROCR rs9574 also associated with early-onset ischemic stroke in the replication sample (OR = 1.08, p = 0.015), but not older-onset stroke. There were no PROCR associations in African-Americans, nor were there any THBD associations in either ethnicity. Conclusion PROCR polymorphisms are associated with early-onset ischemic stroke in Caucasians.Peer reviewe