Regulation of human intestinal T-cell responses by type 1 interferon-STAT1 signaling is disrupted in inflammatory bowel disease

This work was supported by a research fellowship grant from the Crohn’s and Colitis in Childhood Research Association (CICRA) and a small project grant from Crohn’s and Colitis UK (CCUK). We would like to acknowledge Professor Ian Sanderson, who helped with the initial design of this work, and provided important support throughout. We would also like to thank Dr Gary Warne for his advice and assistance in the use of the sorting by flow cytometry. We would also like to thank Dr Raj Lahiri and Professor Graham Foster for the kind gift of the primers for the ISGs (2’5’ OAS and MxA)

Evaluating the drivers of and obstacles to the willingness to use cognitive enhancement drugs: the influence of drug characteristics, social environment, and personal characteristics

Sattler S, Mehlkop G, Graeff P, Sauer C. Evaluating the drivers of and obstacles to the willingness to use cognitive enhancement drugs: the influence of drug characteristics, social environment, and personal characteristics. Substance Abuse Treatment, Prevention, and Policy. 2014;9(1): 8.Background The use of cognitive enhancement (CE) by means of pharmaceutical agents has been the subject of intense debate both among scientists and in the media. This study investigates several drivers of and obstacles to the willingness to use prescription drugs non-medically for augmenting brain capacity. Methods We conducted a web-based study among 2,877 students from randomly selected disciplines at German universities. Using a factorial survey, respondents expressed their willingness to take various hypothetical CE-drugs; the drugs were described by five experimentally varied characteristics and the social environment by three varied characteristics. Personal characteristics and demographic controls were also measured. Results We found that 65.3% of the respondents staunchly refused to use CE-drugs. The results of a multivariate negative binomial regression indicated that respondents’ willingness to use CE-drugs increased if the potential drugs promised a significant augmentation of mental capacity and a high probability of achieving this augmentation. Willingness decreased when there was a high probability of side effects and a high price. Prevalent CE-drug use among peers increased willingness, whereas a social environment that strongly disapproved of these drugs decreased it. Regarding the respondents’ characteristics, pronounced academic procrastination, high cognitive test anxiety, low intrinsic motivation, low internalization of social norms against CE-drug use, and past experiences with CE-drugs increased willingness. The potential severity of side effects, social recommendations about using CE-drugs, risk preferences, and competencies had no measured effects upon willingness. Conclusions These findings contribute to understanding factors that influence the willingness to use CE-drugs. They support the assumption of instrumental drug use and may contribute to the development of prevention, policy, and educational strategies

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

Self-Reported Functional Vision in USH2A-Associated Retinal Degeneration as Measured by the Michigan Retinal Degeneration Questionnaire

Purpose: The purpose of this study was to evaluate self-reported functional vision (FV) and the impact of vision loss in patients with USH2A-associated retinal degeneration using a patient-reported outcome (PRO) measure, the Michigan Retinal Degeneration Questionnaire (MRDQ), to correlate MRDQ scores with well-established visual function measurements. // Design: An observational cross-sectional study (n = 93) of participants who had Usher Syndrome Type 2 (USH2, n = 55) or autosomal recessive non-syndromic retinitis pigmentosa (ARRP; n = 38) associated with biallelic variants in the USH2A gene. // Methods: The study protocol was approved by all ethics boards and informed consent was obtained from each participant. Participants completed the MRDQ at the 48-month study follow-up visit. Disease duration was self-reported by participants. One-way ANOVA was used to compare subgroups (clinical diagnosis, age, disease duration, and full-field stimulus threshold [FST] Blue-Red mediation) on mean scores per domain. Spearman correlation coefficients were used to assess associations between MRDQ domains and visual/retinal function assessments. // Results: Of the study sample, 58% were female participants and the median disease duration was 13 years. MRDQ domains were sensitive to differences between subgroups of clinical diagnosis, age, disease duration, and FST Blue-Red mediation. MRDQ domains correlated with static perimetry, microperimetry, full-field stimulus testing, and best-corrected visual acuity (BCVA). // Conclusions: Self-reported FV measured by the MRDQ, when applied to USH2 and ARRP participants, had good distributional characteristics and correlated well with visual function tests. MRDQ adds a new dimension of understanding on vision-related functioning and establishes this PRO tool as an informative measure in evaluating USH2A outcomes

Tear proteomic analysis of Sjogren syndrome patients with dry eye syndrome by two-dimensional-nano-liquid chromatography coupled with tandem mass spectrometry

We examined the tear film proteome of patients with Sjögren's syndrome (SS) and dry eye syndrome (group A), patients with dry eye symptoms (group B) and normal volunteers (group C). Tear samples were pooled from 8 subjects from each group and were subjected to two-dimensional-nano-liquid chromatography coupled with tandem mass spectrometry (2D-nano-LC-MS/MS). The tear breakup time for group A was significantly reduced compared with group B and C (P < 0.001). Group A (Schirmer I test, 2.13 +/- 2.38 mm/5 min) had markedly lower tear volume than group B (5.94 +/- 4.75 mm/5 min) and C (14.44 +/- 6.57 mm/5 min) (P < 0.001). Group A had significantly higher normalized tear protein content (1.8291 +/- 0.2241 mu g/mm) than group B (1.0839 +/- 0.1120 mu g/mm) (P = 0.001) and C (0.2028 +/- 0.0177 mu g/mm) (P = 0.001). The 2D-nano-LC-MS/MS analysis identified a total of 435 proteins, including 182 (54.8%),247 (74.4%) and 278 (83.7%) in group A, B, and C, respectively, with 56 (16.7%) proteins including defensin alpha 1, clusterin and lactotransferrin unique to group A. In conclusion, dry eye syndrome in SS patients is associated with an altered proteomic profile with dysregulated expression of proteins involved in a variety of important cellular process including inflammation, immunity, and oxidative stress

Evaluation of a combined index of optic nerve structure and function for glaucoma diagnosis

<p>Abstract</p> <p>Background</p> <p>The definitive diagnosis of glaucoma is currently based on congruent damage to both optic nerve structure and function. Given widespread quantitative assessment of both structure (imaging) and function (automated perimetry) in glaucoma, it should be possible to combine these quantitative data to diagnose disease. We have therefore defined and tested a new approach to glaucoma diagnosis by combining imaging and visual field data, using the anatomical organization of retinal ganglion cells.</p> <p>Methods</p> <p>Data from 1499 eyes of glaucoma suspects and 895 eyes with glaucoma were identified at a single glaucoma center. Each underwent Heidelberg Retinal Tomograph (HRT) imaging and standard automated perimetry. A new measure combining these two tests, the structure function index (SFI), was defined in 3 steps: 1) calculate the probability that each visual field point is abnormal, 2) calculate the probability of abnormality for each of the six HRT optic disc sectors, and 3) combine those probabilities with the probability that a field point and disc sector are linked by ganglion cell anatomy. The SFI was compared to the HRT and visual field using receiver operating characteristic (ROC) analysis.</p> <p>Results</p> <p>The SFI produced an area under the ROC curve (0.78) that was similar to that for both visual field mean deviation (0.78) and pattern standard deviation (0.80) and larger than that for a normalized measure of HRT rim area (0.66). The cases classified as glaucoma by the various tests were significantly non-overlapping. Based on the distribution of test values in the population with mild disease, the SFI may be better able to stratify this group while still clearly identifying those with severe disease.</p> <p>Conclusions</p> <p>The SFI reflects the traditional clinical diagnosis of glaucoma by combining optic nerve structure and function. In doing so, it identifies a different subset of patients than either visual field testing or optic nerve head imaging alone. Analysis of prospective data will allow us to determine whether the combined index of structure and function can provide an improved standard for glaucoma diagnosis.</p

Advancing clinical trials for inherited retinal diseases: Recommendations from the second monaciano symposium

Major advances in the study of inherited retinal diseases (IRDs) have placed efforts to develop treatments for these blinding conditions at the forefront of the emerging field of precision medicine. As a result, the growth of clinical trials for IRDs has increased rapidly over the past decade and is expected to further accelerate as more therapeutic possibilities emerge and qualified participants are identified. Although guided by established principles, these specialized trials, requiring analysis of novel outcome measures and endpoints in small patient populations, present multiple challenges relative to study design and ethical considerations. This position paper reviews recent accomplishments and existing challenges in clinical trials for IRDs and presents a set of recommendations aimed at rapidly advancing future progress. The goal is to stimulate discussions among researchers, funding agencies, industry, and policy makers that will further the design, conduct, and analysis of clinical trials needed to accelerate the approval of effective treatments for IRDs, while promoting advocacy and ensuring patient safety

Development and validation of a computerized expert system for evaluation of automated visual fields from the Ischemic Optic Neuropathy Decompression Trial

BACKGROUND: The objective of this report is to describe the methods used to develop and validate a computerized system to analyze Humphrey visual fields obtained from patients with non-arteritic anterior ischemic optic neuropathy (NAION) and enrolled in the Ischemic Optic Neuropathy Decompression Trial (IONDT). The IONDT was a multicenter study that included randomized and non-randomized patients with newly diagnosed NAION in the study eye. At baseline, randomized eyes had visual acuity of 20/64 or worse and non-randomized eyes had visual acuity of better than 20/64 or were associated with patients refusing randomization. Visual fields were measured before treatment using the Humphrey Field Analyzer with the 24-2 program, foveal threshold, and size III stimulus. METHODS: We used visual fields from 189 non-IONDT eyes with NAION to develop the computerized classification system. Six neuro-ophthalmologists ("expert panel") described definitions for visual field patterns defects using 19 visual fields representing a range of pattern defect types. The expert panel then used 120 visual fields, classified using these definitions, to refine the rules, generating revised definitions for 13 visual field pattern defects and 3 levels of severity. These definitions were incorporated into a rule-based computerized classification system run on Excel(® )software. The computerized classification system was used to categorize visual field defects for an additional 95 NAION visual fields, and the expert panel was asked to independently classify the new fields and subsequently whether they agreed with the computer classification. To account for test variability over time, we derived an adjustment factor from the pooled short term fluctuation. We examined change in defects with and without adjustment in visual fields of study participants who demonstrated a visual acuity decrease within 30 days of NAION onset (progressive NAION). RESULTS: Despite an agreed upon set of rules, there was not good agreement among the expert panel when their independent visual classifications were compared. A majority did concur with the computer classification for 91 of 95 visual fields. Remaining classification discrepancies could not be resolved without modifying existing definitions. Without using the adjustment factor, visual fields of 63.6% (14/22) patients with progressive NAION and no central defect, and all (7/7) patients with a paracentral defect, worsened within 30 days of NAION onset. After applying the adjustment factor, the visual fields of the same patients with no initial central defect and 5/7 of the patients with a paracentral defect were seen to worsen. CONCLUSION: The IONDT developed a rule-based computerized system that consistently defines pattern and severity of visual fields of NAION patients for use in a research setting