Reference ranges of the WHO Disability Assessment Schedule (WHODAS 2.0) score and diagnostic validity of its 12-item version in identifying altered functioning in healthy postpartum women.

OBJECTIVES: To compare scores on the 36-item WHO Disability Assessment Schedule 2.0 tool (WHODAS-36) for postpartum women across a continuum of morbidity and to validate the 12-item version (WHODAS-12). METHODS: This is a secondary analysis of the Brazilian retrospective cohort study on long-term repercussions of severe maternal morbidity. We determined mean, median, and percentile values for WHODAS-36 total score and for each domain, and percentile values for WHODAS-12 total score in postpartum women divided into three groups: "no," "nonsevere," and "severe" morbidities. RESULTS: The WHODAS-36 mean total scores were 11.58, 18.31, and 19.19, respectively for no, nonsevere, and severe morbidity. There was a dose-dependent effect on scores for each domain of WHODAS-36 according to the presence and severity of morbidity. The diagnostic validity of WHODAS-12 was determined by comparing it with WHODAS-36 as a "gold standard." The best cut-off point for diagnosing dysfunctionality was the 95th percentile. CONCLUSION: The upward trend of WHODAS-36 total mean value scores of women with no morbidity compared with those with morbidity along a severity continuum may reflect the impact of morbidity on postpartum functioning

Validation of the WHO Disability Assessment Schedule (WHODAS 2.0) 12-item tool against the 36-item version for measuring functioning and disability associated with pregnancy and history of severe maternal morbidity.

OBJECTIVE: To validate the WHO Disability Assessment Schedule 2.0 (WHODAS 2.0) 12-item tool against the 36-item version for measuring functioning and disability associated with pregnancy and the occurrence of maternal morbidity. METHODS: This is a secondary analysis of the Brazilian retrospective cohort study on long-term repercussions of severe maternal morbidity (SMM) among women who delivered at a tertiary facility (COMMAG study). We compared WHODAS-12 and WHODAS-36 scores of women with and without SMM using measures of central tendency and variability, tests for instruments' agreement (Bland-Altman plot), confirmatory factor analysis (CFA), and Cronbach alpha coefficient for internal consistency. RESULTS: The COMMAG study enrolled 638 women up to 5 years postpartum. Although the median WHODAS-36 and -12 scores for all women were statistically different (13.04 and 11.76, respectively; P<0.001), there was a strong linear correlation between them. Furthermore, the mean difference and the differences in variance analyses demonstrated agreement of total scores between the two versions. CFA demonstrated how the WHODAS-12 questions are divided into six previously defined factors and Cronbach alpha showed good internal consistency. CONCLUSION: WHODAS-12 demonstrated agreement with WHODAS-36 for total score and was a good instrument for screening functioning and disability among postpartum women, with and without SMM

The impact of hypertension, hemorrhage, and other maternal morbidities on functioning in the postpartum period as assessed by the WHODAS 2.0 36-item tool.

OBJECTIVE: To assess the scores of postpartum women using the WHO Disability Assessment Schedule 2.0 36-item tool (WHODAS-36), considering different morbidities. METHODS: Secondary analysis of a retrospective cohort of women who delivered at a referral maternity in Brazil and were classified with and without severe maternal morbidity (SMM). WHODAS-36 was used to assess functioning in postpartum women. Percentile distribution of total WHODAS score was compared across three groups: Percentile (P)90. Cases of SMM were categorized and WHODAS-36 score was assessed according to hypertension, hemorrhage, or other conditions. RESULTS: A total of 638 women were enrolled: 64 had mean scores below P90 (41.3). Of women scoring above P>90, those with morbidity had a higher mean score than those without (44.6% vs 36.8%, P=0.879). Women with higher WHODAS-36 scores presented more complications during pregnancy, especially hypertension (47.0% vs 37.5%, P=0.09). Mean scores among women with any complication were higher than those with no morbidity (19.0 vs 14.2, P=0.01). WHODAS-36 scores were higher among women with hypertensive complications (19.9 vs 16.0, P=0.004), but lower among those with hemorrhagic complications (13.8 vs 17.7, P=0.09). CONCLUSIONS: Complications during pregnancy, childbirth, and the puerperium increase long-term WHODAS-36 scores, demonstrating a persistent impact on functioning among women, up to 5 years postpartum

Critical behavior of the two-dimensional N-component Landau-Ginzburg Hamiltonian with cubic anisotropy

We study the two-dimensional N-component Landau-Ginzburg Hamiltonian with cubic anisotropy. We compute and analyze the fixed-dimension perturbative expansion of the renormalization-group functions to four loops. The relations of these models with N-color Ashkin-Teller models, discrete cubic models, planar model with fourth order anisotropy, and structural phase transition in adsorbed monolayers are discussed. Our results for N=2 (XY model with cubic anisotropy) are compatible with the existence of a line of fixed points joining the Ising and the O(2) fixed points. Along this line the exponent $\eta$ has the constant value 1/4, while the exponent $\nu$ runs in a continuous and monotonic way from 1 to $\infty$ (from Ising to O(2)). For N\geq 3 we find a cubic fixed point in the region $u, v \geq 0$, which is marginally stable or unstable according to the sign of the perturbation. For the physical relevant case of N=3 we find the exponents $\eta=0.17(8)$ and $\nu=1.3(3)$ at the cubic transition.Comment: 14 pages, 9 figure

The N-component Ginzburg-Landau Hamiltonian with cubic anisotropy: a six-loop study

We consider the Ginzburg-Landau Hamiltonian with a cubic-symmetric quartic interaction and compute the renormalization-group functions to six-loop order in d=3. We analyze the stability of the fixed points using a Borel transformation and a conformal mapping that takes into account the singularities of the Borel transform. We find that the cubic fixed point is stable for N>N_c, N_c = 2.89(4). Therefore, the critical properties of cubic ferromagnets are not described by the Heisenberg isotropic Hamiltonian, but instead by the cubic model at the cubic fixed point. For N=3, the critical exponents at the cubic and symmetric fixed points differ very little (less than the precision of our results, which is $\lesssim 1$ in the case of $\gamma$ and $\nu$). Moreover, the irrelevant interaction bringing from the symmetric to the cubic fixed point gives rise to slowly-decaying scaling corrections with exponent $\omega_2=0.010(4)$. For N=2, the isotropic fixed point is stable and the cubic interaction induces scaling corrections with exponent $\omega_2 = 0.103(8)$. These conclusions are confirmed by a similar analysis of the five-loop $\epsilon$-expansion. A constrained analysis which takes into account that $N_c = 2$ in two dimensions gives $N_c = 2.87(5)$.Comment: 29 pages, RevTex, new refs added, Phys. Rev. B in pres

Exclusion of mutations in the PRNP, JPH3, TBP, ATN1, CREBBP, POU3F2 and FTL genes as a cause of disease in Portuguese patients with a Huntington-like phenotype

Huntington disease (HD) is an autosomal dominant neurodegenerative disorder characterised by chorea, cognitive impairment, dementia and personality changes, caused by the expansion of a CAG repeat in the HD gene. Often, patients with a similar clinical presentation do not carry expansions of the CAG repeat in this gene [Huntington disease-like (HDL) patients]. We report the genetic analysis of 107 Portuguese patients with an HDL phenotype. The HDL genes PRNP and JPH3, encoding the prion protein and junctophilin-3, respectively, were screened for repeat expansions in these patients. Given the partial clinical overlap of SCA17, DRPLA and neuroferritinopathy with HD, their causative genes (TBP, ATN1, and FTL, respectively) were also analysed. Finally, repeat expansions in two candidate genes, CREBBP and POU3F2, which encode the nuclear transcriptional coactivator CREB-binding protein and the CNS-specific transcription factor N-Oct-3, respectively, were also studied. Expansions of the repetitive tracts of the PRNP, JPH3, TBP, ATN1, CREBBP and POU3F2 genes were excluded in all patients, as were sequence alterations in the FTL gene. Since none of the genes already included in the differential diagnosis of HD was responsible for the disease in our sample, the genetic heterogeneity of the HDL phenotype is still open for investigation.Fundação para a Ciência e a Tecnologia (FCT) and FEDER (grant CBO/33485/99). BIC included in grant CBO/33485/99, respectivel

Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6,809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI