Varying the item format improved the range of measurement in patient-reported outcome measures assessing physical function

BACKGROUND: Physical function (PF) is a core patient-reported outcome domain in clinical trials in rheumatic diseases. Frequently used PF measures have ceiling effects, leading to large sample size requirements and low sensitivity to change. In most of these instruments, the response category that indicates the highest PF level is the statement that one is able to perform a given physical activity without any limitations or difficulty. This study investigates whether using an item format with an extended response scale, allowing respondents to state that the performance of an activity is easy or very easy, increases the range of precise measurement of self-reported PF. METHODS: Three five-item PF short forms were constructed from the Patient-Reported Outcomes Measurement Information System (PROMIS(R)) wave 1 data. All forms included the same physical activities but varied in item stem and response scale: format A ( Are you able to ... ; without any difficulty / unable to do ); format B ( Does your health now limit you ... ; not at all / cannot do ); format C ( How difficult is it for you to ... ; very easy / impossible ). Each short-form item was answered by 2217-2835 subjects. We evaluated unidimensionality and estimated a graded response model for the 15 short-form items and remaining 119 items of the PROMIS PF bank to compare item and test information for the short forms along the PF continuum. We then used simulated data for five groups with different PF levels to illustrate differences in scoring precision between the short forms using different item formats. RESULTS: Sufficient unidimensionality of all short-form items and the original PF item bank was supported. Compared to formats A and B, format C increased the range of reliable measurement by about 0.5 standard deviations on the positive side of the PF continuum of the sample, provided more item information, and was more useful in distinguishing known groups with above-average functioning. CONCLUSIONS: Using an item format with an extended response scale is an efficient option to increase the measurement range of self-reported physical function without changing the content of the measure or affecting the latent construct of the instrument

Layperson perception of reflux-related symptoms

OBJECTIVE: To assess for differences of intended meaning in the description of reflux-related symptoms among otolaryngology patients and clinicians. STUDY DESIGN: Cross-sectional survey-based study. SETTING: Five tertiary, academic otolaryngology practices. METHODS: Between June 2020 and July 2022, a questionnaire consisting of 20 common descriptors of reflux-related symptoms within four domains (throat-, chest-, stomach-, and sensory-related symptoms) was completed by patients. Attending otolaryngologists at five academic medical centers then completed the same survey. The primary outcome was to assess differences in patient and clinician perceptions of reflux-related symptoms. Differences based on geographic location was a secondary outcome. RESULTS: A total of 324 patients and 27 otolaryngologists participated. Patients selected a median of six terms compared with 10.5 for otolaryngologists ( CONCLUSION: There are differences between otolaryngologists and their patients in the interpretation of the symptoms of reflux. Patients tended to have a narrower interpretation of reflux with symptoms primarily limited to classic stomach-related symptoms, while clinicians tended to have a broader definition of reflux that included extra-esophageal manifestations of disease. This has important counseling implications for the clinician, as patients presenting with reflux symptoms may not comprehend the relationship of those symptoms to reflux disease

The Photodetector Array Camera and Spectrometer (PACS) on the Herschel Space Observatory

The Photodetector Array Camera and Spectrometer (PACS) is one of the three science instruments on ESA's far infrared and submillimetre observatory. It employs two Ge:Ga photoconductor arrays (stressed and unstressed) with 16x25 pixels, each, and two filled silicon bolometer arrays with 16x32 and 32x64 pixels, respectively, to perform integral-field spectroscopy and imaging photometry in the 60-210\mu\ m wavelength regime. In photometry mode, it simultaneously images two bands, 60-85\mu\ m or 85-125\mu\m and 125-210\mu\ m, over a field of view of ~1.75'x3.5', with close to Nyquist beam sampling in each band. In spectroscopy mode, it images a field of 47"x47", resolved into 5x5 pixels, with an instantaneous spectral coverage of ~1500km/s and a spectral resolution of ~175km/s. We summarise the design of the instrument, describe observing modes, calibration, and data analysis methods, and present our current assessment of the in-orbit performance of the instrument based on the Performance Verification tests. PACS is fully operational, and the achieved performance is close to or better than the pre-launch predictions

Plasma and Muscle Myostatin in Relation to Type 2 Diabetes

OBJECTIVE: Myostatin is a secreted growth factor expressed in skeletal muscle tissue, which negatively regulates skeletal muscle mass. Recent animal studies suggest a role for myostatin in insulin resistance. We evaluated the possible metabolic role of myostatin in patients with type 2 diabetes and healthy controls. DESIGN: 76 patients with type 2 diabetes and 92 control subjects were included in the study. They were matched for age, gender and BMI. Plasma samples and biopsies from the vastus lateralis muscle were obtained to assess plasma myostatin and expression of myostatin in skeletal muscle. RESULTS: Patients with type 2 diabetes had higher fasting glucose (8.9 versus 5.1 mmol/L, P<0.001), plasma insulin (68.2 versus 47.2 pmol/L, P<0.002) and HOMA2-IR (1.6 versus 0.9, P<0.0001) when compared to controls. Patients with type 2 diabetes had 1.4 (P<0.01) higher levels of muscle myostatin mRNA content than the control subjects. Plasma myostatin concentrations did not differ between patients with type 2 diabetes and controls. In healthy controls, muscle myostatin mRNA correlated with HOMA2-IR (r = 0.30, P<0.01), plasma IL-6 (r = 0.34, P<0.05) and VO2 max (r = -0.26, P<0.05), however, no correlations were observed in patients with type 2 diabetes. CONCLUSIONS: This study supports the idea that myostatin may have a negative effect on metabolism. However, the metabolic effect of myostatin appears to be overruled by other factors in patients with type 2 diabetes

Genome-wide association study identifies 30 loci associated with bipolar disorder.

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P &lt; 1 × 10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P &lt; 5 × 10-8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder

Progress and challenges in glacial lake outburst flood research (2017–2021):a research community perspective

Glacial lake outburst floods (GLOFs) are among the most concerning consequences of retreating glaciers in mountain ranges worldwide. GLOFs have attracted significant attention amongst scientists and practitioners in the past 2 decades, with particular interest in the physical drivers and mechanisms of GLOF hazard and in socioeconomic and other human-related developments that affect vulnerabilities to GLOF events. This increased research focus on GLOFs is reflected in the gradually increasing number of papers published annually. This study offers an overview of recent GLOF research by analysing 594 peer-reviewed GLOF studies published between 2017 and 2021 (Web of Science and Scopus databases), reviewing the content and geographical focus as well as other characteristics of GLOF studies. This review is complemented with perspectives from the first GLOF conference (7-9 July 2021, online) where a global GLOF research community of major mountain regions gathered to discuss the current state of the art of integrated GLOF research. Therefore, representatives from 17 countries identified and elaborated trends and challenges and proposed possible ways forward to navigate future GLOF research, in four thematic areas: (i) understanding GLOFs - timing and processes; (ii) modelling GLOFs and GLOF process chains; (iii) GLOF risk management, prevention and warning; and (iv) human dimensions of GLOFs and GLOF attribution to climate change.Fil: Emmer, Adam. University of Graz; AustriaFil: Allen, Simon K.. Universitat Zurich; Suiza. Universidad de Ginebra; SuizaFil: Carey, Mark. University of Oregon; Estados UnidosFil: Frey, Holger. Universitat Zurich; SuizaFil: Huggel, Christian. Universitat Zurich; SuizaFil: Korup, Oliver. Universitat Potsdam; AlemaniaFil: Mergili, Martin. University of Graz; AustriaFil: Sattar, Ashim. Universitat Zurich; SuizaFil: Veh, Georg. Universitat Potsdam; AlemaniaFil: Chen, Thomas Y.. Columbia University; Estados UnidosFil: Cook, Simon J.. University Of Dundee; Reino Unido. Unesco. Centre For Water Law, Policy And Science; Reino UnidoFil: Correas Gonzalez, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Das, Soumik. Jawaharlal Nehru University; IndiaFil: Diaz Moreno, Alejandro. Reynolds International Ltd; Reino UnidoFil: Drenkhan, Fabian. Pontificia Universidad Católica de Perú; PerúFil: Fischer, Melanie. Universitat Potsdam; AlemaniaFil: Immerzeel, Walter W.. Utrecht University; Países BajosFil: Izagirre, Eñaut. Universidad del País Vasco; EspañaFil: Joshi, Ramesh Chandra. Kumaun University India; IndiaFil: Kougkoulos, Ioannis. American College Of Greece; GreciaFil: Kuyakanon Knapp, Riamsara. University of Oslo; Noruega. University of Cambridge; Estados UnidosFil: Li, Dongfeng. National University Of Singapore; SingapurFil: Majeed, Ulfat. University Of Kashmir; IndiaFil: Matti, Stephanie. Haskoli Islands; IslandiaFil: Moulton, Holly. University of Oregon; Estados UnidosFil: Nick, Faezeh. Utrecht University; Países BajosFil: Piroton, Valentine. Université de Liège; BélgicaFil: Rashid, Irfan. University Of Kashmir; IndiaFil: Reza, Masoom. Kumaun University India; IndiaFil: Ribeiro De Figueiredo, Anderson. Universidade Federal do Rio Grande do Sul; BrasilFil: Riveros, Christian. Instituto Nacional de Investigación En Glaciares y Ecosistemas de Montaña; PerúFil: Shrestha, Finu. International Centre For Integrated Mountain Development Nepal; NepalFil: Shrestha, Milan. Arizona State University; Estados UnidosFil: Steiner, Jakob. International Centre For Integrated Mountain Development Nepal; NepalFil: Walker-Crawford, Noah. Colegio Universitario de Londres; Reino UnidoFil: Wood, Joanne L.. University of Exeter; Reino UnidoFil: Yde, Jacob C.. Western Norway University Of Applied Sciences; Suiz

Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID)

Introduction: Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin's lymphoma in a real-life clinical setting. Methods: Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators. Results: A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0% with systemic lupus erythematosus, 15.7% antineutrophil cytoplasmic antibody-associated granulomatous vasculitides, 15.1% multiple sclerosis and 10.0% pemphigus) from 42 centres received a mean dose of 2,440 mg of rituximab over a median (range) of 194 (180 to 1,407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3% of patients showed no response, 45.1% showed a partial response and 41.6% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician's visual analogue scale; mean improvement from baseline of 12.1 mm). Conclusions: Data from this registry indicate that rituximab is a commonly employed, well-tolerated therapy with potential beneficial effects in standard of care-refractory autoimmune diseases, and support the results from other open-label, uncontrolled studies

New insights in the relation between climate and slope failures at high-elevation sites

Climate change is now unequivocal; however, the type and extent of terrestrial impacts are still widely debated. Among these, the effects on slope stability are receiving a growing attention in recent years, both as terrestrial indicators of climate change and implications for hazard assessment. High-elevation areas are particularly suitable for these studies, because of the presence of the cryosphere, which is particularly sensitive to climate. In this paper, we analyze 358 slope failures which occurred in the Italian Alps in the period 2000–2016, at an elevation above 1500 m a.s.l. We use a statistical-based method to detect climate anomalies associated with the occurrence of slope failures, with the aim to catch an eventual climate signal in the preparation and/or triggering of the considered case studies. We first analyze the probability values assumed by 25 climate variables on the occasion of a slope-failure occurrence. We then perform a dimensionality reduction procedure and come out with a set of four most significant and representative climate variables, in particular heavy precipitation and short-term high temperature. Our study highlights that slope failures occur in association with one or more climate anomalies in almost 92% of our case studies. One or more temperature anomalies are detected in association with most case studies, in combination or not with precipitation (47% and 38%, respectively). Summer events prevail, and an increasing role of positive temperature anomalies from spring to winter, and with elevation and failure size, emerges. While not providing a final evidence of the role of climate warming on slope instability increase at high elevation in recent years, the results of our study strengthen this hypothesis, calling for more extensive and in-depth studies on the subject