Measurement of ocular surface protection under natural blink conditions

abstract: Purpose: To evaluate a new method of measuring ocular exposure in the context of a natural blink pattern through analysis of the variables tear film breakup time (TFBUT), interblink interval (IBI), and tear film breakup area (BUA). Methods: The traditional methodology (Forced-Stare [FS]) measures TFBUT and IBI separately. TFBUT is measured under forced-stare conditions by an examiner using a stopwatch, while IBI is measured as the subject watches television. The new methodology (video capture manual analysis [VCMA]) involves retrospective analysis of video data of fluorescein-stained eyes taken through a slit lamp while the subject watches television, and provides TFBUT and BUA for each IBI during the 1-minute video under natural blink conditions. The FS and VCMA methods were directly compared in the same set of dry-eye subjects. The VCMA method was evaluated for the ability to discriminate between dry-eye subjects and normal subjects. The VCMA method was further evaluated in the dry eye subjects for the ability to detect a treatment effect before, and 10 minutes after, bilateral instillation of an artificial tear solution. Results: Ten normal subjects and 17 dry-eye subjects were studied. In the dry-eye subjects, the two methods differed with respect to mean TFBUTs (5.82 seconds, FS; 3.98 seconds, VCMA; P = 0.002). The FS variables alone (TFBUT, IBI) were not able to successfully distinguish between the dry-eye and normal subjects, whereas the additional VCMA variables, both derived and observed (BUA, BUA/IBI, breakup rate), were able to successfully distinguish between the dry-eye and normal subjects in a statistically significant fashion. TFBUT (P = 0.034) and BUA/IBI (P = 0.001) were able to distinguish the treatment effect of artificial tears in dry-eye subjects. Conclusion: The VCMA methodology provides a clinically relevant analysis of tear film stability measured in the context of a natural blink pattern.The final version of this article, as published in Clinical Ophthalmology, can be viewed online at: https://www.dovepress.com/measurement-of-ocular-surface-protection-under-natural-blink-condition-peer-reviewed-article-OPT

Sustaining Wildlife with Recreation on Public Lands: A Synthesis of Research Findings, Management Practices, and Research Needs

Humans and wildlife interact in multifaceted ways on public lands with both positive and negative outcomes for each group. When managed well, wildlife-based tourism and other forms of recreation can benefit conservation goals. Public lands planners and managers often must decide how to best manage recreational activities and wildlife habitats that overlap spatially and temporally. We conducted an extensive literature review and categorized recreational activity into five types based on the use of motorized equipment, season, and location (terrestrial vs. aquatic), expanding on findings summarized in prior reviews. Our findings provide a reference for public lands planners and managers who need information about how wildlife species respond to recreational activities and to associated changes in their habitats. We also describe management principles gleaned from the literature and outline priority research and administrative study areas to advance our understanding of recreation-wildlife interactions

Humanized Mouse Model of Ovarian Cancer Recapitulates Patient Solid Tumor Progression, Ascites Formation, and Metastasis

Ovarian cancer is the most common cause of death from gynecological cancer. Understanding the biology of this disease, particularly how tumor-associated lymphocytes and fibroblasts contribute to the progression and metastasis of the tumor, has been impeded by the lack of a suitable tumor xenograft model. We report a simple and reproducible system in which the tumor and tumor stroma are successfully engrafted into NOD-scid IL2Rγnull (NSG) mice. This is achieved by injecting tumor cell aggregates derived from fresh ovarian tumor biopsy tissues (including tumor cells, and tumor-associated lymphocytes and fibroblasts) i.p. into NSG mice. Tumor progression in these mice closely parallels many of the events that are observed in ovarian cancer patients. Tumors establish in the omentum, ovaries, liver, spleen, uterus, and pancreas. Tumor growth is initially very slow and progressive within the peritoneal cavity with an ultimate development of tumor ascites, spontaneous metastasis to the lung, increasing serum and ascites levels of CA125, and the retention of tumor-associated human fibroblasts and lymphocytes that remain functional and responsive to cytokines for prolonged periods. With this model one will be able to determine how fibroblasts and lymphocytes within the tumor microenvironment may contribute to tumor growth and metastasis, and will make it possible to evaluate the efficacy of therapies that are designed to target these cells in the tumor stroma

Molecular Cytogenetic Analysis and Resequencing of Contactin Associated Protein-Like 2 in Autism Spectrum Disorders

Autism spectrum disorders (ASD) are a group of related neurodevelopmental syndromes with complex genetic etiology.1 We identified a de novo chromosome 7q inversion disrupting Autism susceptibility candidate 2 (AUTS2) and Contactin Associated Protein-Like 2 (CNTNAP2) in a child with cognitive and social delay. We focused our initial analysis on CNTNAP2 based on our demonstration of disruption of Contactin 4 (CNTN4) in a patient with ASD;2 the recent finding of rare homozygous mutations in CNTNAP2 leading to intractable seizures and autism;3 and in situ and biochemical analyses reported herein that confirm expression in relevant brain regions and demonstrate the presence of CNTNAP2 in the synaptic plasma membrane fraction of rat forebrain lysates. We comprehensively resequenced CNTNAP2 in 635 patients and 942 controls. Among patients, we identified a total of 27 nonsynonymous changes; 13 were rare and unique to patients and 8 of these were predicted to be deleterious by bioinformatic approaches and/or altered residues conserved across all species. One variant at a highly conserved position, I869T, was inherited by four affected children in three unrelated families, but was not found in 4010 control chromosomes (p = 0.014). Overall, this resequencing data demonstrated a modest nonsignificant increase in the burden of rare variants in cases versus controls. Nonethless, when viewed in light of two independent studies published in this issue of AJHG showing a relationship between ASD and common CNTNAP2 alleles,4,5 the cytogenetic and mutation screening data suggest that rare variants may also contribute to the pathophysiology of ASD, but place limits on the magnitude of this contribution

Applying refinement to the use of mice and rats in rheumatoid arthritis research

Rheumatoid arthritis (RA) is a painful, chronic disorder and there is currently an unmet need for effective therapies that will benefit a wide range of patients. The research and development process for therapies and treatments currently involves in vivo studies, which have the potential to cause discomfort, pain or distress. This Working Group report focuses on identifying causes of suffering within commonly used mouse and rat ‘models’ of RA, describing practical refinements to help reduce suffering and improve welfare without compromising the scientific objectives. The report also discusses other, relevant topics including identifying and minimising sources of variation within in vivo RA studies, the potential to provide pain relief including analgesia, welfare assessment, humane endpoints, reporting standards and the potential to replace animals in RA research

Evidence of the validity and accuracy of the Brazilian social attitude of students scale towards politics

Objetivou-se apresentar as evidências de validade e confiabilidade de uma escala brasileira para medir atitudes políticas de estudantes brasileiros de nível superior ante seus comportamentos políticos. O estudo teve uma amostra de abrangência nacional (N = 445), com estudantes brasileiros oriundos de distintos estados. Os resultados indicaram uma estrutura empírica sustentável (teste de Kaiser-Meyer-Olkin - KMO = 0,81), com indicadores psicométricos considerados adequados à mensuração das atitudes políticas. Três fatores empíricos foram identificados: grau de conhecimento sobre política (15 itens, cargas fatoriais entre 0,31 e 0,82, alfa = 0,82, eigenvalue = 5,07 e variância explicada = 18,78 %), afetos relativos à política (7 itens, cargas fatoriais entre 0,41 e 0,58, alfa = 0,72, eigenvalue = 3,17 e variância explicada = 11,73 %) e intenções de comportamento político (2 itens, cargas fatoriais entre 0,70 e 0,72, alfa = 0,80, eigenvalue = 1,8 e variância explicada = 6,8 %). Conclui-se que os resultados fortalecem a estrutura fatorial original da escala e mostram sua utilidade para a identificação de atitudes sociais ante comportamentos políticos.El objetivo de la presente investigación fue presentar las pruebas de confiabilidad y validez de una escala brasileña para medir las actitudes políticas de los estudiantes universitarios brasileños ante su comportamiento político. El estudio contó con una muestra nacional (N = 445) de estudiantes brasileños de diferentes Estados. Los resultados indicaron una estructura empírica sustentable (KMO = .81), con indicadores psicométricos que se consideran adecuados para la medición de las actitudes políticas. Específicamente, se identificaron tres factores empíricos: nivel de conocimiento sobre la política (15 ítems, cargas factoriales entre .31 y .82, alfa = .82, eigenvalue = 5.07 y varianza explicada = 18.78 %), sentimientos acerca de la política (7 ítems, factoriales de .41 y .58, alfa = .72, eigenvalue = 3.17 y varianza explicada = 11.73 °/o) e intenciones del comportamiento político (2 ítems, factoriales de .70 y .72, alfa = .80, eigenvalue = 1.8 y varianza explicada = 6.8 %). Se llegó a la conclusión de que los resultados apoyan la estructura factorial original de la escala y muestran su utilidad en la identificación de las actitudes sociales ante la conducta política.The objective of this study was to present the validity and reliability evidences of a Brazilian scale to measure the political attitudes of Brazilian higher education students regarding their political behavior. The study had a nationwide sample (N = 445), with Brazilian students from different states. The results indicated a sustainable empirical structure (KMO = 0.81), with psychometric indicators considered adequate to the measurement of political attitudes. Three empirical factors were identified: degree of political knowledge (15 items, factorial loads between 0.31 and 0.82, alpha = 0.82, eigenvalue = 5.07 and explained variance = 18.78%), feelings about politics (7 items, factorial loads between 0.41 and 0.58, alpha = 0.72, eigenvalue = 3.17 and explained variance = 11.73%) and intentions of political behavior (2 items, factorial loads between 0, 70 and 0.72, alpha = 0.80, eigenvalue = 1.8 and explained variance = 6.8%). It is concluded that the results strengthen the original factorial structure of the scale and show its utility for the identification of social attitudes regarding political behaviors

Common variation in the miR-659 binding-site of GRN is a major risk factor for TDP43-positive frontotemporal dementia

Loss-of-function mutations in progranulin (GRN) cause ubiquitin- and TAR DNA-binding protein 43 (TDP-43)-positive frontotemporal dementia (FTLD-U), a progressive neurodegenerative disease affecting ∼10% of early-onset dementia patients. Here we expand the role of GRN in FTLD-U and demonstrate that a common genetic variant (rs5848), located in the 3′-untranslated region (UTR) of GRN in a binding-site for miR-659, is a major susceptibility factor for FTLD-U. In a series of pathologically confirmed FTLD-U patients without GRN mutations, we show that carriers homozygous for the T-allele of rs5848 have a 3.2-fold increased risk to develop FTLD-U compared with homozygous C-allele carriers (95% CI: 1.50–6.73). We further demonstrate that miR-659 can regulate GRN expression in vitro, with miR-659 binding more efficiently to the high risk T-allele of rs5848 resulting in augmented translational inhibition of GRN. A significant reduction in GRN protein was observed in homozygous T-allele carriers in vivo, through biochemical and immunohistochemical methods, mimicking the effect of heterozygous loss-of-function GRN mutations. In support of these findings, the neuropathology of homozygous rs5848 T-allele carriers frequently resembled the pathological FTLD-U subtype of GRN mutation carriers. We suggest that the expression of GRN is regulated by miRNAs and that common genetic variability in a miRNA binding-site can significantly increase the risk for FTLD-U. Translational regulation by miRNAs may represent a common mechanism underlying complex neurodegenerative disorders

Target for improvement: a cluster randomised trial of public involvement in quality-indicator prioritisation (intervention development and study protocol)

<p>Abstract</p> <p>Background</p> <p>Public priorities for improvement often differ from those of clinicians and managers. Public involvement has been proposed as a way to bridge the gap between professional and public clinical care priorities but has not been studied in the context of quality-indicator choice. Our objective is to assess the feasibility and impact of public involvement on quality-indicator choice and agreement with public priorities.</p> <p>Methods</p> <p>We will conduct a cluster randomised controlled trial comparing quality-indicator prioritisation with and without public involvement. In preparation for the trial, we developed a 'menu' of quality indicators, based on a systematic review of existing validated indicator sets. Participants (public representatives, clinicians, and managers) will be recruited from six participating sites. In intervention sites, public representatives will be involved through direct participation (public representatives, clinicians, and managers will deliberate together to agree on quality-indicator choice and use) and consultation (individual public recommendations for improvement will be collected and presented to decision makers). In control sites, only clinicians and managers will take part in the prioritisation process. Data on quality-indicator choice and intended use will be collected. Our primary outcome will compare quality-indicator choice and agreement with public priorities between intervention and control groups. A process evaluation based on direct observation, videorecording, and participants' assessment will be conducted to help explain the study's results. The marginal cost of public involvement will also be assessed.</p> <p>Discussion</p> <p>We identified 801 quality indicators that met our inclusion criteria. An expert panel agreed on a final set of 37 items containing validated quality indicators relevant for chronic disease prevention and management in primary care. We pilot tested our public-involvement intervention with 27 participants (11 public representatives and 16 clinicians and managers) and our study instruments with an additional 21 participants, which demonstrated the feasibility of the intervention and generated important insights and adaptations to engage public representatives more effectively. To our knowledge, this study is the first trial of public involvement in quality-indicator prioritisation, and its results could foster more effective upstream engagement of patients and the public in clinical practice improvement.</p> <p>Trial registration</p> <p><a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2496">NTR2496</a> (Netherlands National Trial Register, <url>http://www.trialregister.nl</url>).</p