Support for the higher-order factor structure of the WHODAS 2.0 self-report version in a Dutch outpatient psychiatric setting

PURPOSE: Previous studies of the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) interview version suggested a second-order model, with a general disability factor and six factors on a lower level. The goal of this study is to investigate if we can find support for a similar higher-order factor structure of the 36-item self-report version of the WHODAS 2.0 in a Dutch psychiatric outpatient sample. We aim to give special attention to the differences between the non-working group sample and the working group sample. Additionally, we intend to provide preliminary norms for clinical interpretation of the WHODAS 2.0 scores in psychiatric settings. METHODS: Patients seeking specialized ambulatory treatment, primarily for depressive or anxiety symptoms, completed the WHODAS 2.0 as part of the initial interview. The total sample consisted of 770 patients with a mean age of 37.5 years (SD = 13.3) of whom 280 were males and 490 were females. Several factorial compositions (i.e., one unidimensional model and two second-order models) were modeled using confirmatory factor analysis (CFA). Descriptive statistics, model-fit statistics, reliability of the (sub)scales, and preliminary norms for interpreting test scores are reported. RESULTS: For the non-working group, the second-order model with a general disability factor and six factors on a lower level, provided an adequate fit. Whereas, for the working group, the second-order model with a general disability factor and seven factors on a lower level seemed more appropriate. The WHODAS 2.0 36-item self-report form showed adequate levels of reliability. Percentile ranks and normalized T-scores are provided to aid clinical evaluations. CONCLUSION: Our results lend support for a factorial structure of the WHODAS 2.0 36-item self-report version that is comparable to the interview version. While we conjecture that a seven-factor solution might give a better reflection of item content and item variance, further research is needed to assess the clinical relevance of such a model. At this point, we recommend using the second-order structure with six factors that matches past findings of the interview form

High-vacuum-compatible high-power Faraday isolators for gravitational-wave interferometers

Faraday isolators play a key role in the operation of large-scale gravitational-wave detectors. Second-generation gravitational-wave interferometers such as the Advanced Laser Interferometer Gravitational-Wave Observatory (LIGO) and Advanced Virgo will use high-average-power cw lasers (up to 200 W) requiring specially designed Faraday isolators that are immune to the effects resulting from the laser beam absorption–degraded isolation ratio, thermal lensing, and thermally induced beam steering. In this paper, we present a comprehensive study of Faraday isolators designed specifically for high-performance operation in high-power gravitational-wave interferometers

A novel cyclic biased agonist of the apelin receptor, MM07, is disease modifying in the rat monocrotaline model of pulmonary arterial hypertension.

BACKGROUND AND PURPOSE: Apelin is an endogenous vasodilatory and inotropic peptide that is down-regulated in human pulmonary arterial hypertension, although the density of the apelin receptor is not significantly attenuated. We hypothesised that a G protein-biased apelin analogue MM07, which is more stable than the endogenous apelin peptide, may be beneficial in this condition with the advantage of reduced β-arrestin-mediated receptor internalisation with chronic use. EXPERIMENTAL APPROACH: Male Sprague-Dawley rats received either monocrotaline to induce pulmonary arterial hypertension or saline and then daily i.p. injections of either MM07 or saline for 21 days. The extent of disease was assessed by right ventricular catheterisation, cardiac MRI, and histological analysis of the pulmonary vasculature. The effect of MM07 on signalling, proliferation, and apoptosis of human pulmonary artery endothelial cells was investigated. KEY RESULTS: MM07 significantly reduced the elevation of right ventricular systolic pressure and hypertrophy induced by monocrotaline. Monocrotaline-induced changes in cardiac structure and function, including right ventricular end-systolic and end-diastolic volumes, ejection fraction, and left ventricular end-diastolic volume, were attenuated by MM07. MM07 also significantly reduced monocrotaline-induced muscularisation of small pulmonary blood vessels. MM07 stimulated endothelial NOS phosphorylation and expression, promoted proliferation, and attenuated apoptosis of human pulmonary arterial endothelial cells in vitro. CONCLUSION AND IMPLICATIONS: Our findings suggest that chronic treatment with MM07 is beneficial in this animal model of pulmonary arterial hypertension by addressing disease aetiology. These data support the development of G protein-biased apelin receptor agonists with improved pharmacokinetic profiles for use in human disease.the Medical Research Council MC_PC_14116 [to APD] Wellcome Trust [107715/Z/15/Z to APD], Programme in Metabolic and Cardiovascular Disease [096822/Z/11/Z to PY; 203814/Z/16/A to TLW], Parke Davis Fellowship [to PY], British Heart Foundation [FS/14/59/31282 to CR] and in part by the National Institute for Health Research Cambridge Biomedical Research Centre

The use of 2-D speckle tracking echocardiography in assessing adolescent athletes with left ventricular hypertrabeculation meeting the criteria for left ventricular non-compaction cardiomyopathy

BACKGROUND: Current echocardiographic criteria cannot accurately differentiate exercise induced left ventricular (LV) hypertrabeculation in athletes from LV non-compaction cardiomyopathy (LVNC). This study aims to evaluate the role of speckle tracking echocardiography (STE) in characterising LV myocardial mechanics in healthy adolescent athletes with and without LVNC echocardiographic criteria. METHODS: Adolescent athletes evaluated at three sports academies between 2014 and 2019 were considered for this observational study. Those meeting the Jenni criteria for LVNC (end-systolic non-compacted/compacted myocardium ratio > 2 in any short axis segment) were considered LVNC+ and the rest LVNC-. Peak systolic LV longitudinal strain (Sl), circumferential strain (Sc), rotation (Rot), corresponding strain rates (SRl/c) and segmental values were calculated and compared using a non-inferiority approach. RESULTS: A total of 417 participants were included, mean age 14.5 ± 1.7 years, of which 6.5% were LVNC+ (n = 27). None of the athletes showed any additional LVNC clinical criteria. All average Sl, SRl Sc, SRc and Rot values were no worse in the LVNC+ group compared to LVNC- (p values range 0.0003-0.06), apart from apical SRc (p = 0.2). All 54 segmental measurements (Sl/Sc SRl/SRc and Rot) had numerically comparable means in both LVNC+ and LVNC-, of which 69% were also statistically non-inferior. CONCLUSIONS: Among healthy adolescent athletes, 6.5% met the echocardiographic criteria for LVNC, but showed normal LV STE parameters, in contrast to available data on paediatric LVNC describing abnormal myocardial function. STE could better characterise the myocardial mechanics of athletes with LV hypertrabeculation, thus allowing the transition from structural to functional LVNC diagnosis, especially in suspected physiological remodelling

The management of heart failure cardiogenic shock:an international RAND appropriateness panel

Background: Observational data suggest that the subset of patients with heart failure related CS (HF-CS) now predominate critical care admissions for CS. There are no dedicated HF-CS randomised control trials completed to date which reliably inform clinical practice or clinical guidelines. We sought to identify aspects of HF-CS care where both consensus and uncertainty may exist to guide clinical practice and future clinical trial design, with a specific focus on HF-CS due to acute decompensated chronic HF. Methods: A 16-person multi-disciplinary panel comprising of international experts was assembled. A modified RAND/University of California, Los Angeles, appropriateness methodology was used. A survey comprising of 34 statements was completed. Participants anonymously rated the appropriateness of each statement on a scale of 1 to 9 (1–3 as inappropriate, 4–6 as uncertain and as 7–9 appropriate). Results: Of the 34 statements, 20 were rated as appropriate and 14 were rated as inappropriate. Uncertainty existed across all three domains: the initial assessment and management of HF-CS; escalation to temporary Mechanical Circulatory Support (tMCS); and weaning from tMCS in HF-CS. Significant disagreement between experts (deemed present when the disagreement index exceeded 1) was only identified when deliberating the utility of thoracic ultrasound in the immediate management of HF-CS. Conclusion: This study has highlighted several areas of practice where large-scale prospective registries and clinical trials in the HF-CS population are urgently needed to reliably inform clinical practice and the synthesis of future societal HF-CS guidelines

Omics\u27 biomarkers associated with chronic low back pain: Protocol of a retrospective longitudinal study

Introduction Chronic low back pain (CLBP) produces considerable direct costs as well as indirect burdens for society, industry and health systems. CLBP is characterised by heterogeneity, inclusion of several pain syndromes, different underlying molecular pathologies and interaction with psychosocial factors that leads to a range of clinical manifestations. There is still much to understand in the underlying pathological processes and the non-psychosocial factors which account for differences in outcomes. Biomarkers that may be objectively used for diagnosis and personalised, targeted and cost-effective treatment are still lacking. Therefore, any data that may be obtained at the-omics\u27 level (glycomics, Activomics and genome-wide association studies-GWAS) may be helpful to use as dynamic biomarkers for elucidating CLBP pathogenesis and may ultimately provide prognostic information too. By means of a retrospective, observational, case-cohort, multicentre study, we aim to investigate new promising biomarkers potentially able to solve some of the issues related to CLBP. Methods and analysis The study follows a two-phase, 1:2 case-control model. A total of 12 000 individuals (4000 cases and 8000 controls) will be enrolled; clinical data will be registered, with particular attention to pain characteristics and outcomes of pain treatments. Blood samples will be collected to perform-omics studies. The primary objective is to recognise genetic variants associated with CLBP; secondary objectives are to study glycomics and Activomics profiles associated with CLBP. Ethics and dissemination The study is part of the PainOMICS project funded by European Community in the Seventh Framework Programme. The study has been approved from competent ethical bodies and copies of approvals were provided to the European Commission before starting the study. Results of the study will be reviewed by the Scientific Board and Ethical Committee of the PainOMICS Consortium. The scientific results will be disseminated through peer-reviewed journals. Trial registration number NCT02037789; Pre-results

The advanced LIGO input optics

The advanced LIGO gravitational wave detectors are nearing their design sensitivity and should begin taking meaningful astrophysical data in the fall of 2015. These resonant optical interferometers will have unprecedented sensitivity to the strains caused by passing gravitational waves. The input optics play a significant part in allowing these devices to reach such sensitivities. Residing between the pre-stabilized laser and the main interferometer, the input optics subsystem is tasked with preparing the laser beam for interferometry at the sub-attometer level while operating at continuous wave input power levels ranging from 100 mW to 150 W. These extreme operating conditions required every major component to be custom designed. These designs draw heavily on the experience and understanding gained during the operation of Initial LIGO and Enhanced LIGO. In this article, we report on how the components of the input optics were designed to meet their stringent requirements and present measurements showing how well they have lived up to their design

The use of 2-D speckle tracking echocardiography in differentiating healthy adolescent athletes with right ventricular outflow tract dilation from patients with arrhythmogenic cardiomyopathy

AIMS: Echocardiographic assessment of adolescent athletes for arrhythmogenic cardiomyopathy (ACM) can be challenging owing to right ventricular (RV) exercise-related remodelling, particularly RV outflow tract (RVOT) dilation. The aim of this study is to evaluate the role of RV 2-D speckle tracking echocardiography (STE) in comparing healthy adolescent athletes with and without RVOT dilation to patients with ACM. METHODS AND RESULTS: A total of 391 adolescent athletes, mean age 14.5 ± 1.7 years, evaluated at three sports academies between 2014 and 2019 were included, and compared to previously reported ACM patients (n = 38 definite and n = 39 borderline). Peak systolic RV free wall (RVFW-Sl), global and segmental strain (Sl), and corresponding strain rates (SRl) were calculated. The participants meeting the major modified Task Force Criteria (mTFC) for RVOT dilation were defined as mTFC+ (n = 58, 14.8%), and the rest as mTFC- (n = 333, 85.2%). Mean RVFW-Sl was -27.6 ± 3.4% overall, -28.2 ± 4.1% in the mTFC+ group and - 27.5 ± 3.3% in the mTFC- group. mTFC+ athletes had normal RV-FW-Sl when compared to definite (-29% vs -19%, p < 0.001) and borderline ACM (-29% vs -21%, p < 0.001) cohorts. In addition, all mean global and regional Sl and SRl values were no worse in the mTFC+ group compared to the mTFC- (p values range < 0.0001 to 0.1, inferiority margin of 2% and 0.1 s-1 respectively). CONCLUSIONS: In athletes with RVOT dilation meeting the major mTFC, STE evaluation of the RV can demostrate normal function and differentiate physiological remodelling from pathological changes found in ACM, improving screening in grey-area cases

The Advanced LIGO Input Optics

The advanced LIGO gravitational wave detectors are nearing their design sensitivity and should begin taking meaningful astrophysical data in the fall of 2015. These resonant optical interferometers will have unprecedented sensitivity to the strains caused by passing gravitational waves. The input optics play a significant part in allowing these devices to reach such sensitivities. Residing between the pre-stabilized laser and the main interferometer, the input optics subsystem is tasked with preparing the laser beam for interferometry at the sub-attometer level while operating at continuous wave input power levels ranging from 100 mW to 150 W. These extreme operating conditions required every major component to be custom designed. These designs draw heavily on the experience and understanding gained during the operation of Initial LIGO and Enhanced LIGO. In this article, we report on how the components of the input optics were designed to meet their stringent requirements and present measurements showing how well they have lived up to their design