In vivo imaging of the airway wall in asthma: fibered confocal fluorescence microscopy in relation to histology and lung function

<p>Abstract</p> <p>Background</p> <p>Airway remodelling is a feature of asthma including fragmentation of elastic fibres observed in the superficial elastin network of the airway wall. Fibered confocal fluorescence microscopy (FCFM) is a new and non-invasive imaging technique performed during bronchoscopy that may visualize elastic fibres, as shown by <it>in vitro </it>spectral analysis of elastin powder. We hypothesized that FCFM images capture <it>in vivo </it>elastic fibre patterns within the airway wall and that such patterns correspond with airway histology. We aimed to establish the concordance between the bronchial elastic fibre pattern in histology and FCFM. Second, we examined whether elastic fibre patterns in histology and FCFM were different between asthmatic subjects and healthy controls. Finally, the association between these patterns and lung function parameters was investigated.</p> <p>Methods</p> <p>In a cross-sectional study comprising 16 subjects (8 atopic asthmatic patients with controlled disease and 8 healthy controls) spirometry and bronchoscopy were performed, with recording of FCFM images followed by endobronchial biopsy at the airway main carina. Elastic fibre patterns in histological sections and FCFM images were scored semi-quantitatively. Agreement between histology and FCFM was analysed using linearly weighted kappa κ_w.</p> <p>Results</p> <p>The patterns observed in histological sections and FCFM images could be divided into 3 distinct groups. There was good agreement between elastic fibre patterns in histology and FCFM patterns (κ_w0.744). The semi-quantitative pattern scores were not different between asthmatic patients and controls. Notably, there was a significant difference in post-bronchodilator FEV₁%predicted between the different patterns by histology (p = 0.001) and FCFM (p = 0.048), regardless of asthma or atopy.</p> <p>Conclusion</p> <p>FCFM captures the elastic fibre pattern within the airway wall in humans <it>in vivo</it>. The association between post-bronchodilator FEV₁%predicted and both histological and FCFM elastic fibre patterns points towards a structure-function relationship between extracellular matrix in the airway wall and lung function.</p> <p>Trial registration</p> <p>Netherlands Trial Register <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=NTR1306">NTR1306</a></p

Defining tumor growth in vestibular schwannomas:a volumetric inter-observer variability study in contrast-enhanced T1-weighted MRI

Introduction:For patients with vestibular schwannomas (VS), the need for reliable volumetric tumor monitoring is important. Currently, a volumetric cutoff of 20% increase in tumor volume is widely used to define tumor growth in VS. This study investigates the volumetric limits of agreement (LoA) of VS by an inter-observer study.Methods:This retrospective study included 100 VS patients who underwent contrast-enhanced T1-weighted MRI. Five observers volumetrically annotated the images. Observer agreement and reliability was measured using the LoA, estimated using the limits of agreement with the mean (LOAM) method, and the intraclass correlation coefficient (ICC). Influence of imaging parameters and tumor characteristics were assessed using univariable and multivariable linear regression analysis.Results:The 100 patients had an average median tumor volume of 903 mm3 (IQR: 193-3101). Peritumoral cysts were found in 6 patients. Patients were divided into four volumetric size categories based on tumor volume quartile. The smallest tumor volume quartile showed a LOAM relative to the mean of 26.8%, whereas for the largest tumor volume quartile this figure was found to be 7.3% and when excluding peritumoral cysts: 4.8%. Of all imagingparameters and tumor characteristics, only tumor volume was associated with the LoA (adjusted B=-0.001 [P=0.003]).Conclusion:Agreement limits within volumetric annotation of VS are affected by tumor volume, since the LoA improves with increasing tumor volume. As a result, for tumors larger than 200 mm3, growth can reliably be detected at an earlier stage, compared to the currently widely used cutoff of 20%.

The outcome of non-residential youth care compared to residential youth care: A multilevel meta-analysis

Objective: This multilevel meta-analysis compared the outcomes of Treatment Foster Care Oregon for Adolescents (TFCO-A) and home-based treatment programs (HBT) with residential youth care for children and youth aged 0 to 23 years. Methods: A total of 145 effect sizes for different types of behavioral problems were derived from 24 controlled studies (n = 16,943 participants). A three-level random-effects meta-analysis was conducted. Results: We found a small statistically significant overall effect (d = 0.21), 95% CI [0.090-0.338], which indicated that non-residential youth care was slightly more effective than residential youth care. However, moderator analysis revealed that TFCO-A yielded a larger effect size (d = 0.36) than HBT (d = 0.08). Conclusions: Our findings suggest that youth treated in treatment foster care have better outcomes than youth in residential care, which is not true for children who are treated at home. Therefore, in case of out-of-home placement treatment foster care should be the first option. Given that residential care has no additional value for youth who are treated a

Perspective and Costing in Cost-Effectiveness Analysis, 1974-2018

OBJECTIVE: Our objective was to examine perspective and costing approaches used in cost-effectiveness analyses (CEAs) and the distribution of reported incremental cost-effectiveness ratios (ICERs). METHODS: We analyzed the Tufts Medical Center's CEA and Global Health CEA registries, containing 6907 cost-per-quality-adjusted-life-year (QALY) and 698 cost-per-disability-adjusted-life-year (DALY) studies published through 2018. We examined how often published CEAs included non-health consequences and their impact on ICERs. We also reviewed 45 country-specific guidelines to examine recommended analytic perspectives. RESULTS: Study authors often mis-specified or did not clearly state the perspective used. After re-classification by registry reviewers, a healthcare sector or payer perspective was most prevalent (74%). CEAs rarely included unrelated medical costs and impacts on non-healthcare sectors. The most common non-health consequence included was productivity loss in the cost-per-QALY studies (12%) and patient transportation in the cost-per-DALY studies (21%). Of 19,946 cost-per-QALY ratios, the median ICER was $US26,000/QALY (interquartile range [IQR] 2900-110,000), and 18$US430/DALY (IQR 67-3400), and 8% were cost saving and DALY averting. Based on 16 cost-per-QALY studies (2017-2018) reporting 68 ICERs from both the healthcare sector and societal perspectives, the median ICER from a societal perspective ($US22,710/QALY [IQR 11,991-49,603]) was more favorable than from a healthcare sector perspective ($US30,402/QALY [IQR 10,486-77,179]). Most governmental guidelines (67%) recommended either a healthcare sector or a payer perspective. CONCLUSION: Researchers should justify and be transparent about their choice of perspective and costing approaches. The use of the impact inventory and reporting of disaggregate outcomes can reduce inconsistencies and confusion

Correction to : Perspective and Costing in Cost‑Effectiveness Analysis, 1974-2018

The article Perspective and Costing in Cost-Effectiveness Analysis

\u3ci\u3eSDH5\u3c/i\u3e, a Gene Required for Flavination of Succinate Dehydrogenase, Is Mutated in Paraganglioma

Mammalian mitochondria contain about 1100 proteins, nearly 300 of which are uncharacterized. Given the well-established role of mitochondrial defects in human disease, functional characterization of these proteins may shed new light on disease mechanisms. Starting with yeast as a model system, we investigated an uncharacterized but highly conserved mitochondrial protein (named here Sdh5). Both yeast and human Sdh5 interact with the catalytic subunit of the succinate dehydrogenase (SDH) complex, a component of both the electron transport chain and the tricarboxylic acid cycle. Sdh5 is required for SDH-dependent respiration and for Sdh1 flavination (incorporation of the flavin adenine dinucleotide cofactor). Germline loss-of-function mutations in the human SDH5 gene, located on chromosome 11q13.1, segregate with disease in a family with hereditary paraganglioma, a neuroendocrine tumor previously linked to mutations in genes encoding SDH subunits. Thus, a mitochondrial proteomics analysis in yeast has led to the discovery of a human tumor susceptibility gene

Tuberculosis Microepidemics among Dispersed Migrants, Birmingham, UK, 2004-2013

MIRU-VNTR typing was supported by the Public Health England National TB Strain Typing Project. M.M. is funded by the UK Clinical Research Collaboration Modernising Medical Microbiology Consortium. C.B. is funded by the Heart of Birmingham Primary Care Trust and Public Health England

\u3ci\u3eSDH5\u3c/i\u3e, a Gene Required for Flavination of Succinate Dehydrogenase, Is Mutated in Paraganglioma

Mammalian mitochondria contain about 1100 proteins, nearly 300 of which are uncharacterized. Given the well-established role of mitochondrial defects in human disease, functional characterization of these proteins may shed new light on disease mechanisms. Starting with yeast as a model system, we investigated an uncharacterized but highly conserved mitochondrial protein (named here Sdh5). Both yeast and human Sdh5 interact with the catalytic subunit of the succinate dehydrogenase (SDH) complex, a component of both the electron transport chain and the tricarboxylic acid cycle. Sdh5 is required for SDH-dependent respiration and for Sdh1 flavination (incorporation of the flavin adenine dinucleotide cofactor). Germline loss-of-function mutations in the human SDH5 gene, located on chromosome 11q13.1, segregate with disease in a family with hereditary paraganglioma, a neuroendocrine tumor previously linked to mutations in genes encoding SDH subunits. Thus, a mitochondrial proteomics analysis in yeast has led to the discovery of a human tumor susceptibility gene

Multicentre performance evaluation of the E170 Module for MODULAR ANALYTICS

The E170 module was evaluated at 13 sites in an international multicentre study. The objective of the study was to assess the analytical performance of 49 analytes, and to collect feedback on the system's reliability and practicability. The typical, within-run coefficients of variation (CVs) for most of the quantitative assays ranged between 1 and 2% while a range of 2-4% was achieved with the infectious disease methods. Total precision CVs were found to be within the manufacturer's expected performance ranges, demonstrating good concordance of the system's measuring channels and a high reproducibility during the 2-4-week trial period. The functional sensitivity of 11 selected assays met the clinical requirements (e.g., thyreotroponin (TSH) 0.008 mU/l, troponin T 0.02 µg/l, total prostate-specific antigen (PSA) 0.03 µg/l). The E170 showed no drift during an 8-hour period and no relevant reagent carryover. Accuracy was confirmed by ring trial experiments and method comparisons vs. Elecsys® 2010. The reliability and practicability of the system's hardware and software met with, or even exceeded, the evaluator's requirements. Workflow studies showed that E170 can cover the combined workload of various routine analysers in a variety of laboratory environment. Throughput and sample processing time requirements were achieved while personnel ‘hands-on-time' could be reduce

Mittelfristige Prognose der österreichischen Wirtschaft 2003-2007: Ökonometrisches Forschungsprogramm des Instituts für Höhere Studien

aus dem Inhaltsverzeichnis: Einleitung und Zusammenfassung; Die internationale Konjunktur; Die österreichische Außenwirtschaft; Perspektiven der Inlandskonjunktur; Monetäre Prognose; Tabellenanhang