Outlooks and Opinions of Practicing Physical Therapists Regarding Direct Access in Indiana

poster abstractIntroduction: Indiana is one of the remaining states that requires by state law a referral to initiate treatment by a licensed physical therapist (PT) and therefore does not allow consumers direct access to physical therapy services. In 2009, the Indiana Chapter of the American Physical Therapy Association (APTA) and Indiana University jointly funded a study to investigate the opinions of licensed physical therapists on direct access to physical therapy services. Purpose: The study investigated physical therapists opinions residing in the state of Indiana on four main issues: Direct access—desire for and willingness to achieve Scope of care—differential diagnosis and clinical skills Liability—perceived impact of direct access Manipulation practices—competence and confidence Methods: The researchers used an online program, SurveyMonkey©, to design an 18-question survey. The sample was recruited via a mailing list from the Indiana State Board of Health which included all the licensed physical therapists within the state of Indiana. A letter explaining the purpose of the study including a hyperlink to the survey and a hard copy of the survey was mailed to 3,350 physical therapists. The survey respondents could either choose to complete the survey online via the hyperlink or on the hard copy provided and return via a provided selfaddressed stamped envelope for survey return. Results: There were 1,379 respondents which accounted for a 42% return rate. APTA membership was analyzed with 39.5% of the respondents being APTA members and the remaining 60.5% being non-members. The collective responses to specific questions were reported by a five-level Likert response scale. The majority of respondents want direct access in the state of Indiana, with the average response being 4.13/5.00. However, proportionately the willingness of respondents to be actively involved is much lower, with the average response being 3.23/5.00. The majority (61%) believed their liability would increase with direct access. The terminal degrees for the respondents surveyed were varied with the majority, 48.6%, holding a Bachelor’s degree. The responses of participants were significantly influenced by their degree/level of training with higher levels of training being consistently associated with more favorable attitudes to direct access issues. Discussion /Clinical Relevance: The high return rate and passionate responses confirm these issues are important to PT’s practicing in Indiana and the majority of those surveyed are in favor of direct access to physical therapy services without compromise of the current scope of care. The results of this study may have implications for health policy regarding direct access to physical therapy services within the state of Indiana. In particular to help redirect efforts toward dispelling myths, promoting grassroots efforts and encouraging teamwork in our peers

Farmer perspectives of the on-farm and off-farm pros and cons of planted multifunctional riparian margins

The planting of riparian margins is a policy option for pastoral farmers in response to land use induced environmental issues such as declining water quality, stream bank erosion, and loss of aquatic and terrestrial habitat. We elicited the views and experiences as to pros and cons of planting riparian margins from two sets of dairy farmers from Taranaki, New Zealand: those who are or have planted riparian margins, and those who have not yet done so. Those farmers who have planted riparian margins identified 21 positive aspects of riparian margin plantings and 11 negative aspects of riparian margin plantings. Perceived benefits identified by this group include water quality, increased biodiversity, the provision of cultural ecosystem services, immediate direct benefits to farm management and the farm system, and in some instances increased productivity on-farm. In contrast, those farmers that had fenced but not planted their riparian margins did not consider that riparian margin plantings could add further benefits to that which could be achieved by excluding stock from waterways, and associated only negative perceptions with riparian margin plantings. Planting riparian margins is not cost neutral and will not deliver anticipated environmental benefits in every situation. However, we argue that riparian margin plantings are an important ecological infrastructure investment that needs to be captured within a wider policy framework, the benefits of which extend beyond the mitigation of a single negative externality generated by land use practices, such as nutrient loss, and contribute to a multifunctional landscape

The evolution of drug resistance in clinical isolates of Candida albicans

Candida albicans is both a member of the healthy human microbiome and a major pathogen in immunocompromised individuals. Infections are typically treated with azole inhibitors of ergosterol biosynthesis often leading to drug resistance. Studies in clinical isolates have implicated multiple mechanisms in resistance, but have focused on large-scale aberrations or candidate genes, and do not comprehensively chart the genetic basis of adaptation. Here, we leveraged next-generation sequencing to analyze 43 isolates from 11 oral candidiasis patients. We detected newly selected mutations, including single-nucleotide polymorphisms (SNPs), copy-number variations and loss-of-heterozygosity (LOH) events. LOH events were commonly associated with acquired resistance, and SNPs in 240 genes may be related to host adaptation. Conversely, most aneuploidies were transient and did not correlate with drug resistance. Our analysis also shows that isolates also varied in adherence, filamentation, and virulence. Our work reveals new molecular mechanisms underlying the evolution of drug resistance and host adaptation.National Science Foundation (U.S.). Graduate Research Fellowship ProgramHoward Hughes Medical InstituteHelen Hay Whitney Foundation (Postdoctoral Fellowship)Alfred P. Sloan FoundationNational Institutes of Health (U.S.) (Grant 8DP1CA174427)National Institutes of Health (U.S.) (Grant 2R01CA119176-01

Biometal Dyshomeostasis in Olfactory Mucosa of Alzheimer's Disease Patients

Olfactory function, orchestrated by the cells of the olfactory mucosa at the rooftop of the nasal cavity, is disturbed early in the pathogenesis of Alzheimer's disease (AD). Biometals including zinc and calcium are known to be important for sense of smell and to be altered in the brains of AD patients. Little is known about elemental homeostasis in the AD patient olfactory mucosa. Here we aimed to assess whether the disease-related alterations to biometal homeostasis observed in the brain are also reflected in the olfactory mucosa. We applied RNA sequencing to discover gene expression changes related to metals in olfactory mucosal cells of cognitively healthy controls, individuals with mild cognitive impairment and AD patients, and performed analysis of the elemental content to determine metal levels. Results demonstrate that the levels of zinc, calcium and sodium are increased in the AD olfactory mucosa concomitantly with alterations to 17 genes related to metal-ion binding or metal-related function of the protein product. A significant elevation in alpha-2-macroglobulin, a known metal-binding biomarker correlated with brain disease burden, was observed on the gene and protein levels in the olfactory mucosa cells of AD patients. These data demonstrate that the olfactory mucosa cells derived from AD patients recapitulate certain impairments of biometal homeostasis observed in the brains of patients.Peer reviewe

A phase Ib/IIa clinical trial of dantrolene sodium in patients with Wolfram syndrome

BACKGROUNDWolfram syndrome is a rare ER disorder characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, and progressive neurodegeneration. Although there is no treatment for Wolfram syndrome, preclinical studies in cell and rodent models suggest that therapeutic strategies targeting ER calcium homeostasis, including dantrolene sodium, may be beneficial.METHODSBased on results from preclinical studies on dantrolene sodium and ongoing longitudinal studies, we assembled what we believe is the first-ever clinical trial in pediatric and adult Wolfram syndrome patients with an open-label phase Ib/IIa trial design. The primary objective was to assess the safety and tolerability of dantrolene sodium in adult and pediatric Wolfram syndrome patients. Secondary objectives were to evaluate the efficacy of dantrolene sodium on residual pancreatic β cell functions, visual acuity, quality-of-life measures related to vision, and neurological functions.RESULTSDantrolene sodium was well tolerated by Wolfram syndrome patients. Overall, β cell functions were not significantly improved, but there was a significant correlation between baseline β cell functions and change in β cell responsiveness (R2, P = 0.004) after 6-month dantrolene therapy. Visual acuity and neurological functions were not improved by 6-month dantrolene sodium. Markers of inflammatory cytokines and oxidative stress, such as IFN-γ, IL-1β, TNF-α, and isoprostane, were elevated in subjects.CONCLUSIONThis study justifies further investigation into using dantrolene sodium and other small molecules targeting the ER for treatment of Wolfram syndrome.TRIAL REGISTRATIONClinicalTrials.gov identifier NCT02829268FUNDINGNIH/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (DK112921, DK113487, DK020579), NIH/National Center for Advancing Translational Sciences (NCATS) (TR002065, TR000448), NIH training grant (F30DK111070), Silberman Fund, Ellie White Foundation, Snow Foundation, Unravel Wolfram Syndrome Fund, Stowe Fund, Eye Hope Foundation, Feiock Fund, Washington University Institute of Clinical and Translational Sciences grant UL1TR002345 from NIH/NCATS, Bursky Center for Human Immunology & Immunotherapy Programs

“Lest we forget” : An overview of Australia’s response to the recovery and identification of unrecovered historic military remains

Peer reviewedPostprin

Single-Cell RNA-Seq Analysis of Olfactory Mucosal Cells of Alzheimer's Disease Patients

Olfaction is orchestrated by olfactory mucosal cells located in the upper nasal cavity. Olfactory dysfunction manifests early in several neurodegenerative disorders including Alzheimer's disease, however, disease-related alterations to the olfactory mucosal cells remain poorly described. The aim of this study was to evaluate the olfactory mucosa differences between cognitively healthy individuals and Alzheimer's disease patients. We report increased amyloid-beta secretion in Alzheimer's disease olfactory mucosal cells and detail cell-type-specific gene expression patterns, unveiling 240 differentially expressed disease-associated genes compared to the cognitively healthy controls, and five distinct cell populations. Overall, alterations of RNA and protein metabolism, inflammatory processes, and signal transduction were observed in multiple cell populations, suggesting their role in Alzheimer's disease-related olfactory mucosa pathophysiology. Furthermore, the single-cell RNA-sequencing proposed alterations in gene expression of mitochondrially located genes in AD OM cells, which were verified by functional assays, demonstrating altered mitochondrial respiration and a reduction of ATP production. Our results reveal disease-related changes of olfactory mucosal cells in Alzheimer's disease and demonstrate the utility of single-cell RNA sequencing data for investigating molecular and cellular mechanisms associated with the disease.Peer reviewe

Performance measurement : challenges for tomorrow

This paper demonstrates that the context within which performance measurement is used is changing. The key questions posed are: Is performance measurement ready for the emerging context? What are the gaps in our knowledge? and Which lines of enquiry do we need to pursue? A literature synthesis conducted by a team of multidisciplinary researchers charts the evolution of the performance-measurement literature and identifies that the literature largely follows the emerging business and global trends. The ensuing discussion introduces the currently emerging and predicted future trends and explores how current knowledge on performance measurement may deal with the emerging context. This results in identification of specific challenges for performance measurement within a holistic systems-based framework. The principle limitation of the paper is that it covers a broad literature base without in-depth analysis of a particular aspect of performance measurement. However, this weakness is also the strength of the paper. What is perhaps most significant is that there is a need for rethinking how we research the field of performance measurement by taking a holistic systems-based approach, recognizing the integrated and concurrent nature of challenges that the practitioners, and consequently the field, face