Fidelity Assessment in Community Programs: An Approach to Validating Simplified Methodology.

Fidelity to intervention protocol is linked to best outcomes for individuals with autism spectrum disorder (ASD; see Boyd & Corley [Autism 5(4):430-441, 2001]; Pellecchia et al. [J Autism Dev Disord 45(9):2917-2927, 2015]); however, fidelity measurement tools that are both accurate and feasible for community use are often not available. In this paper we explore methods for validated simplification of fidelity assessment procedures toward the goal of increased use in clinical practice. Video recordings (n = 36) of therapists working with children with ASD were coded using three variations of fidelity assessment methodology (trial-by-trial, 5-point Likert Scale, and 3-point Likert Scale), and the results were compared for exact agreement, mastery criterion agreement, and overall reliability. The results indicated overall a very high percentage of exact agreement (mean 99.44%, range 94.4-100%) and excellent reliability (mean Krippendorff's alpha [Kα] 1.0) between the trial-by-trial and 5-point Likert Scale across all components; however, the 3-point method may be viewed as being the more feasible strategy within community programs

Walking for transportation in Hong Kong Chinese urban elders: a cross-sectional study on what destinations matter and when

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EDN1 Lys198Asn is Associated with Diabetic Retinopathy in Type 2 Diabetes

Purpose: We tested the hypothesis that genetic variants in vasoactive and angiogenic factors regulating the retina vasculature contribute to the development of diabetic retinopathy (DR). Methods: A case-control study was performed to study the genetic association between DR and polymorphic variants of EDN1 (Lys198Asn), LTA (IVS1–80C>A, IVS1–206G>C, IVS1–252>G), eNOS (Glu298Asp), and ITGA2 (BgI II) in a Chinese population with type 2 diabetes mellitus. A well defined population with type 2 diabetes, consisting of 127 controls and 216 DR patients, was recruited. Results: A higher frequency of the Asn/Asn genotype of EDN1 was found in individuals with at least 10 years of diabetes and no retinopathy (controls) compared with DR patients with any duration of diabetes (DR: 2.3%; control: 11.0%; p=0.0002). The Asn allele was also more frequent in controls than DR patients (DR: 16.4%; control: 29.5%; p=0.007). Multiple logistic regression analysis showed that the Asn/Asn genotype was the factor most significantly associated with reduced risk of DR (odds ratio=0.19; 95% CI: 0.07-0.53; p=0.002) and with late onset of diabetes (Asn/Asn: 59 years; Lys/Lys + Lys/Asn: 53 years; p=0.02). Moreover, the Lys/Lys genotype was more common among patients with nonproliferative (75.7%) than proliferative DR (56.9%; p=0.008). The distributions of Lys198Asn alleles in hypertension did not differ from normotensive subjects. No associations between DR and polymorphisms of LTA, eNOS, or ITGA2 were detected, and there were no detectable gene-gene or gene-environmental interactions among the polymorphisms.Conclusions The Asn/Asn genotype of EDN1 was associated with a reduced risk of DR and with delayed onset of type 2 diabetes

Library as Scholarly Publishing Partner: Keys to Success

Many academic libraries are looking at new ways to add value when they deliver services to faculty, and one potential area where the library can provide new services is in partnering with academic staff to support the dissemination of faculty research. Librarians have traditionally helped faculty researchers at the beginning of the research cycle, with the discovery and delivery of information sources. However, they are now playing a role at the end of the research cycle, providing services that support scholarly publishing. This paper examines library participation in faculty-led publishing ventures. In particular, it explores the value that smaller research libraries can provide to faculty editors through journal hosting, which will be analysed through an examination of the successful migration of the Australian Journal of Teacher Education, a faculty-administered journal at Edith Cowan University in Perth, Western Australia, to the University’s institutional repository. This transition provided library staff members at Edith Cowan University opportunities to develop new knowledge and skills in journal publishing, while meeting the journal’s need for a better way to manage a growing influx of article submissions. The resultant faculty-library partnership enabled more effective management of the journal and has contributed to its growing success. The evaluative framework developed to enable assessment of the success of this journal’s transition can help other libraries demonstrate the success of their own journal hosting ventures

Clinical actionability of comprehensive genomic profiling for management of rare or refractory cancers

Background. The frequency with which targeted tumor sequencing results will lead to implemented change in care is unclear. Prospective assessment of the feasibility and limitations of using genomic sequencing is critically important. Methods. A prospective clinical study was conducted on 100 patients with diverse-histology, rare, or poor-prognosis cancers to evaluate the clinical actionability of a Clinical Laboratory Improvement Amendments (CLIA)-certified, comprehensive genomic profiling assay (FoundationOne), using formalin-fixed, paraffin-embedded tumors. The primary objectives were to assess utility, feasibility, and limitations of genomic sequencing for genomically guided therapy or other clinical purpose in the setting of a multidisciplinary molecular tumor board. Results. Of the tumors from the 92 patients with sufficient tissue, 88 (96%) had at least one genomic alteration (average 3.6, range 0–10). Commonly altered pathways included p53 (46%), RAS/RAF/MAPK (rat sarcoma; rapidly accelerated fibrosarcoma; mitogen-activated protein kinase) (45%), receptor tyrosine kinases/ligand (44%), PI3K/AKT/mTOR (phosphatidylinositol-4,5-bisphosphate 3-kinase; protein kinase B; mammalian target of rapamycin) (35%), transcription factors/regulators (31%), and cell cycle regulators (30%). Many low frequency but potentially actionable alterations were identified in diverse histologies. Use of comprehensive profiling led to implementable clinical action in 35% of tumors with genomic alterations, including genomically guided therapy, diagnostic modification, and trigger for germline genetic testing. Conclusion. Use of targeted next-generation sequencing in the setting of an institutional molecular tumor board led to implementable clinical action in more than one third of patients with rare and poor-prognosis cancers. Major barriers to implementation of genomically guided therapy were clinical status of the patient and drug access. Early and serial sequencing in the clinical course and expanded access to genomically guided early-phase clinical trials and targeted agents may increase actionability. Implications for Practice: Identification of key factors that facilitate use of genomic tumor testing results and implementation of genomically guided therapy may lead to enhanced benefit for patients with rare or difficult to treat cancers. Clinical use of a targeted next-generation sequencing assay in the setting of an institutional molecular tumor board led to implementable clinical action in over one third of patients with rare and poor prognosis cancers. The major barriers to implementation of genomically guided therapy were clinical status of the patient and drug access both on trial and off label. Approaches to increase actionability include early and serial sequencing in the clinical course and expanded access to genomically guided early phase clinical trials and targeted agents

Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients.

Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB

Genetic Factors Leading to Chronic Epstein–Barr Virus Infection and Nasopharyngeal Carcinoma in South East China: Study Design, Methods and Feasibility

Nasopharyngeal carcinoma (NPC) is a complex disease caused by a combination of Epstein-Barr virus chronic infection, the environment and host genes in a multi-step process of carcinogenesis. The identity of genetic factors involved in the development of chronic Epstein-Barr virus infection and NPC remains elusive, however. Here, we describe a two-phase, population-based, case-control study of Han Chinese from Guangxi province, where the NPC incidence rate rises to a high of 25-50 per 100,000 individuals. Phase I, powered to detect single gene associations, enrolled 984 subjects to determine feasibility, to develop infrastructure and logistics and to determine error rates in sample handling. A microsatellite screen of Phase I study participants, genotyped for 319 alleles from 34 microsatellites spanning an 18-megabase region of chromosome 4 (4p15.1-q12), previously implicated by a linkage analysis of familial NPC, found 14 alleles marginally associated with developing NPC or chronic immunoglobulin A production (p = 0.001-0.03). These associations lost significance after applying a correction for multiple tests. Although the present results await confirmation, the Phase II study population has tripled patient enrolment and has included environmental covariates, offering the potential to validate this and other genomic regions that influence the onset of NPC