56 research outputs found
Day-to-day Variability of Stuttering
Variability has long been known to be a primary feature of the disorder of stuttering (Bloodstein & Bernstein Ratner, 2008; Costello & Ingham, 1984; Yaruss, 1997a, 1997b). Many factors that affect variability have been investigated (Brown, 1937; Johnson & Brown, 1935; Quarrington, Conway, & Siegel, 1962) yet the typical range of variability experienced by speakers remains unknown. This study will examine the speech of six adult speakers in three spontaneous speaking situations and two reading tasks. The frequency, duration, and types of stuttered events that occur on the tasks will be compared within and between speakers. The focus will be on describing variability in stuttering frequency and duration within speakers and attempting to detect consistent patterns between speakers
Multivariate analysis of electrophysiological diversity of Xenopus visual neurons during development and plasticity
Abstract Biophysical properties of neurons become increasingly diverse over development, but mechanisms underlying and constraining this diversity are not fully understood. Here we investigate electrophysiological characteristics of Xenopus tadpole midbrain neurons across development and during homeostatic plasticity induced by patterned visual stimulation. We show that in development tectal neuron properties not only change on average, but also become increasingly diverse. After sensory stimulation, both electrophysiological diversity and functional differentiation of cells are reduced. At the same time, the amount of cross-correlations between cell properties increase after patterned stimulation as a result of homeostatic plasticity. We show that tectal neurons with similar spiking profiles often have strikingly different electrophysiological properties, and demonstrate that changes in intrinsic excitability during development and in response to sensory stimulation are mediated by different underlying mechanisms. Overall, this analysis and the accompanying dataset provide a unique framework for further studies of network maturation in Xenopus tadpoles
IL-22 regulates lymphoid chemokine production and assembly of tertiary lymphoid organs
The series of events leading to tertiary lymphoid organ (TLO) formation in mucosal organs following tissue damage remain unclear. Using a virus-induced model of autoantibody formation in the salivary glands of adult mice, we demonstrate that IL-22 provides a mechanistic link between mucosal infection, B-cell recruitment, and humoral autoimmunity. IL-22 receptor engagement is necessary and sufficient to promote differential expression of chemokine (C-X-C motif) ligand 12 and chemokine (C-X-C motif) ligand 13 in epithelial and fibroblastic stromal cells that, in turn, is pivotal for B-cell recruitment and organization of the TLOs. Accordingly, genetic and therapeutic blockade of IL-22 impairs and reverses TLO formation and autoantibody production. Our work highlights a critical role for IL-22 in TLO-induced pathology and provides a rationale for the use of IL-22–blocking agents in B-cell–mediated autoimmune conditions
The Comprehensive Complication Index (CCI®) is a Novel Cost Assessment Tool for Surgical Procedures
OBJECTIVE The aim of this study was to identify a readily available, reproducible, and internationally applicable cost assessment tool for surgical procedures. SUMMARY OF BACKGROUND DATA Strong economic pressure exists worldwide to slow down the rising of health care costs. Postoperative morbidity significantly impacts on cost in surgical patients. The comprehensive complication index (CCI), reflecting overall postoperative morbidity, may therefore serve as a new marker for cost. METHODS Postoperative complications and total costs from a single tertiary center were prospectively collected (2014 to 2016) up to 3 months after surgery for a variety of abdominal procedures (n = 1388). CCI was used to quantify overall postoperative morbidity. Pearson correlation coefficient (rpears) was calculated for cost and CCI. For cost prediction, a linear regression model based on CCI, age, and type of surgery was developed and validated in an international cohort of patients. RESULTS We found a high correlation between CCI and overall cost (rpears = 0.75) with the strongest correlation for more complex procedures. The prediction model performed very well (R = 0.82); each 10-point increase in CCI corresponded to a 14% increase to the baseline cost. Additional 12% of baseline cost must be added for patients older than 50 years, or 24% for those over 70 years. The validation cohorts showed a good match of predicted and observed cost. CONCLUSION Overall postoperative morbidity correlates highly with cost. The CCI together with the type of surgery and patient age is a novel and reliable predictor of expenses in surgical patients. This finding may enable objective cost comparisons among centers, procedures, or over time obviating the need to look at complex country-specific cost calculations (www.assessurgery.com)
Using Biotic Interaction Networks for Prediction in Biodiversity and Emerging Diseases
Networks offer a powerful tool for understanding and visualizing inter-species ecological and evolutionary interactions. Previously considered examples, such as trophic networks, are just representations of experimentally observed direct interactions. However, species interactions are so rich and complex it is not feasible to directly observe more than a small fraction. In this paper, using data mining techniques, we show how potential interactions can be inferred from geographic data, rather than by direct observation. An important application area for this methodology is that of emerging diseases, where, often, little is known about inter-species interactions, such as between vectors and reservoirs. Here, we show how using geographic data, biotic interaction networks that model statistical dependencies between species distributions can be used to infer and understand inter-species interactions. Furthermore, we show how such networks can be used to build prediction models. For example, for predicting the most important reservoirs of a disease, or the degree of disease risk associated with a geographical area. We illustrate the general methodology by considering an important emerging disease - Leishmaniasis. This data mining methodology allows for the use of geographic data to construct inferential biotic interaction networks which can then be used to build prediction models with a wide range of applications in ecology, biodiversity and emerging diseases
The Autism - Tics, AD/HD and other Comorbidities inventory (A-TAC): further validation of a telephone interview for epidemiological research
<p>Abstract</p> <p>Background</p> <p>Reliable, valid, and easy-to-administer instruments to identify possible caseness and to provide proxies for clinical diagnoses are needed in epidemiological research on child and adolescent mental health.</p> <p>The aim of this study is to provide further validity data for a parent telephone interview focused on Autism - Tics, Attention-deficit/hyperactivity disorder (AD/HD), and other Comorbidities (A-TAC), for which reliability and preliminary validation data have been previously reported.</p> <p>Methods</p> <p>Parents of 91 children clinically diagnosed at a specialized Child Neuropsychiatric Clinic, 366 control children and 319 children for whom clinical diagnoses had been previously assigned were interviewed by the A-TAC over the phone. Interviewers were blind to clinical information. Different scores from the A-TAC were compared to the diagnostic outcome.</p> <p>Results</p> <p>Areas under ROC curves for interview scores as predictors of clinical diagnoses were around 0.95 for most disorders, including autism spectrum disorders (ASDs), attention deficit/hyperactivity disorder (AD/HD), tic disorders, developmental coordination disorders (DCD) and learning disorders, indicating excellent screening properties. Screening cut-off scores with sensitivities above 0.90 (0.95 for ASD and AD/HD) were established for most conditions, as well as cut-off scores to identify proxies to clinical diagnoses with specificities above 0.90 (0.95 for ASD and AD/HD).</p> <p>Conclusions</p> <p>The previously reported validity of the A-TAC was supported by this larger replication study using broader scales from the A-TAC-items and a larger number of diagnostic categories. Short versions of algorithms worked as well as larger. Different cut-off levels for screening versus identifying proxies for clinical diagnoses are warranted. Data on the validity for mood problems and oppositional defiant/conduct problems are still lacking. Although the A-TAC is principally intended for epidemiological research and general investigations, the instrument may be useful as a tool to collect information in clinical practice as well.</p
Oral abstracts 3: RA Treatment and outcomesO13. Validation of jadas in all subtypes of juvenile idiopathic arthritis in a clinical setting
Background: Juvenile Arthritis Disease Activity Score (JADAS) is a 4 variable composite disease activity (DA) score for JIA (including active 10, 27 or 71 joint count (AJC), physician global (PGA), parent/child global (PGE) and ESR). The validity of JADAS for all ILAR subtypes in the routine clinical setting is unknown. We investigated the construct validity of JADAS in the clinical setting in all subtypes of JIA through application to a prospective inception cohort of UK children presenting with new onset inflammatory arthritis. Methods: JADAS 10, 27 and 71 were determined for all children in the Childhood Arthritis Prospective Study (CAPS) with complete data available at baseline. Correlation of JADAS 10, 27 and 71 with single DA markers was determined for all subtypes. All correlations were calculated using Spearman's rank statistic. Results: 262/1238 visits had sufficient data for calculation of JADAS (1028 (83%) AJC, 744 (60%) PGA, 843 (68%) PGE and 459 (37%) ESR). Median age at disease onset was 6.0 years (IQR 2.6-10.4) and 64% were female. Correlation between JADAS 10, 27 and 71 approached 1 for all subtypes. Median JADAS 71 was 5.3 (IQR 2.2-10.1) with a significant difference between median JADAS scores between subtypes (p < 0.01). Correlation of JADAS 71 with each single marker of DA was moderate to high in the total cohort (see Table 1). Overall, correlation with AJC, PGA and PGE was moderate to high and correlation with ESR, limited JC, parental pain and CHAQ was low to moderate in the individual subtypes. Correlation coefficients in the extended oligoarticular, rheumatoid factor negative and enthesitis related subtypes were interpreted with caution in view of low numbers. Conclusions: This study adds to the body of evidence supporting the construct validity of JADAS. JADAS correlates with other measures of DA in all ILAR subtypes in the routine clinical setting. Given the high frequency of missing ESR data, it would be useful to assess the validity of JADAS without inclusion of the ESR. Disclosure statement: All authors have declared no conflicts of interest. Table 1Spearman's correlation between JADAS 71 and single markers DA by ILAR subtype ILAR Subtype Systemic onset JIA Persistent oligo JIA Extended oligo JIA Rheumatoid factor neg JIA Rheumatoid factor pos JIA Enthesitis related JIA Psoriatic JIA Undifferentiated JIA Unknown subtype Total cohort Number of children 23 111 12 57 7 9 19 7 17 262 AJC 0.54 0.67 0.53 0.75 0.53 0.34 0.59 0.81 0.37 0.59 PGA 0.63 0.69 0.25 0.73 0.14 0.05 0.50 0.83 0.56 0.64 PGE 0.51 0.68 0.83 0.61 0.41 0.69 0.71 0.9 0.48 0.61 ESR 0.28 0.31 0.35 0.4 0.6 0.85 0.43 0.7 0.5 0.53 Limited 71 JC 0.29 0.51 0.23 0.37 0.14 -0.12 0.4 0.81 0.45 0.41 Parental pain 0.23 0.62 0.03 0.57 0.41 0.69 0.7 0.79 0.42 0.53 Childhood health assessment questionnaire 0.25 0.57 -0.07 0.36 -0.47 0.84 0.37 0.8 0.66 0.4
RA-MAP, molecular immunological landscapes in early rheumatoid arthritis and healthy vaccine recipients
Rheumatoid arthritis (RA) is a chronic inflammatory disorder with poorly defined aetiology characterised by synovial inflammation with variable disease severity and drug responsiveness. To investigate the peripheral blood immune cell landscape of early, drug naive RA, we performed comprehensive clinical and molecular profiling of 267 RA patients and 52 healthy vaccine recipients for up to 18 months to establish a high quality sample biobank including plasma, serum, peripheral blood cells, urine, genomic DNA, RNA from whole blood, lymphocyte and monocyte subsets. We have performed extensive multi-omic immune phenotyping, including genomic, metabolomic, proteomic, transcriptomic and autoantibody profiling. We anticipate that these detailed clinical and molecular data will serve as a fundamental resource offering insights into immune-mediated disease pathogenesis, progression and therapeutic response, ultimately contributing to the development and application of targeted therapies for RA.</p
Maternal hyperleptinemia is associated with male offspring’s altered vascular function and structure in mice
Children of mothers with gestational diabetes have greater risk of developing hypertension but little is known about the mechanisms by which this occurs. The objective of this study was to test the hypothesis that high maternal concentrations of leptin during pregnancy, which are present in mothers with gestational diabetes and/or obesity, alter blood pressure, vascular structure and vascular function in offspring. Wildtype (WT) offspring of hyperleptinemic, normoglycemic, Lepr db/+ dams were compared to genotype matched offspring of WT-control dams. Vascular function was assessed in male offspring at 6, and at 31 weeks of age after half the offspring had been fed a high fat, high sucrose diet (HFD) for 6 weeks. Blood pressure was increased by HFD but not affected by maternal hyperleptinemia. On a standard diet, offspring of hyperleptinemic dams had outwardly remodeled mesenteric arteries and an enhanced vasodilatory response to insulin. In offspring of WT but not Leprdb/+ dams, HFD induced vessel hypertrophy and enhanced vasodilatory responses to acetylcholine, while HFD reduced insulin responsiveness in offspring of hyperleptinemic dams. Offspring of hyperleptinemic dams had stiffer arteries regardless of diet. Therefore, while maternal hyperleptinemia was largely beneficial to offspring vascular health under astandard diet, it had detrimental effects in offspring fed HFD. These results suggest that circulating maternal leptin concentrations may interact with other factors in the pre- and post-natal environments to contribute to altered vascular function in offspring of diabetic pregnancie
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