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Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3–19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8–144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries. http://purl.org/eprint/status/PeerReviewed published version Article

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10−8) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for ∼11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction. B.C.A.C. was funded through a European Community Seventh Framework Programme under grant agreement no 223175 (HEALTH-F2-2009-223175; COGS); Cancer Research UK (C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692); the National Institutes of Health Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), R01 grants (CA128978, CA176785, CA192393), and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAME-ON initiative); the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, the Breast Cancer Res. Foundation, and the Ovarian Cancer Research Fund. CIMBA genotyping was supported by National Institutes of Health grant (CA128978); the Department of Defence (W81XWH-10-1-0341); and the Breast Cancer Res. Foundation. CIMBA data management and data analysis were supported by Cancer Research UK grants C12292/A11174 and C1287/A10118. This study made use of data generated by the Wellcome Trust Case Control consortium. Functional studies were supported by the Florida Breast Cancer Foundation. A full description of funding and acknowledgments is provided in Supplementary Note 1.

The kidney sessions of the 2017 Banff Conference focused on 2 areas: clinical implications of inflammation in areas of interstitial fibrosis and tubular atrophy (i‐IFTA) and its relationship to T cell–mediated rejection (TCMR), and the continued evolution of molecular diagnostics, particularly in the diagnosis of antibody‐mediated rejection (ABMR). In confirmation of previous studies, it was independently demonstrated by 2 groups that i‐IFTA is associated with reduced graft survival. Furthermore, these groups presented that i‐IFTA, particularly when involving >25% of sclerotic cortex in association with tubulitis, is often a sequela of acute TCMR in association with underimmunosuppression. The classification was thus revised to include moderate i‐IFTA plus moderate or severe tubulitis as diagnostic of chronic active TCMR. Other studies demonstrated that certain molecular classifiers improve diagnosis of ABMR beyond what is possible with histology, C4d, and detection of donor‐specific antibodies (DSAs) and that both C4d and validated molecular assays can serve as potential alternatives and/or complements to DSAs in the diagnosis of ABMR. The Banff ABMR criteria are thus updated to include these alternatives. Finally, the present report paves the way for the Banff scheme to be part of an integrative approach for defining surrogate endpoints in next‐generation clinical trials. The Banff consortium presents revisions to the diagnostic criteria for T cell– and antibody‐mediated kidney transplant rejection, including specific criteria for chronic active T cell–mediated rejection, plus prospects for integrative endpoints in clinical trials. See related articles on pages 321, 364, and 377.

Abstract Objectives The purpose of this study was to assess the feasibility and safety of transcarotid transcatheter aortic valve replacement (TAVR). Background Many candidates for TAVR have challenging vascular anatomy that precludes transfemoral access. Transcarotid arterial access may be an option for such patients. Methods The French Transcarotid TAVR Registry is a voluntary database that prospectively collected patient demographics, procedural characteristics, and clinical outcomes among patients undergoing transcarotid TAVR. Outcomes are reported according to the updated Valve Academic Research Consortium criteria. Results Among 96 patients undergoing transcarotid TAVR at 3 French sites (2009 to 2013), the mean age and Society of Thoracic Surgeons predicted risk of mortality were 79.4 ± 9.2 years and 7.1 ± 4.1%, respectively. Successful carotid artery access was achieved in all patients. The Medtronic CoreValve (Medtronic, Inc., Minneapolis, Minnesota) (n = 89; 92.7%) and Edwards SAPIEN valves (Edwards Lifesciences, Irvine, California) (n = 7; 7.3%) were used. Procedural complications included: valve embolization (3.1%), requirement for a second valve (3.1%), and tamponade (4.2%). There were no major bleeds or major vascular complications related to the access site. There were 3 (3.1%) procedural deaths and 6 (6.3%) deaths at 30 days. The 1-year mortality rate was 16.7%. There were 3 (3.1%) cases of Valve Academic Research Consortium–defined in-hospital stroke (n = 0) or transient ischemic attack (TIA) (n = 3). None of these patients achieved the criteria for stroke and none manifested new ischemic lesions on cerebral computed tomography or magnetic resonance imaging. At 30 days, a further 3 TIAs were observed, giving an overall stroke/TIA rate of 6.3%. Conclusions Transcarotid vascular access for TAVR is feasible and is associated with encouraging short- and medium-term clinical outcomes. Prospective studies are required to ascertain if transcarotid TAVR yields equivalent results to other nonfemoral vascular access routes.

We show that, in a sufficiently large population satisfying certain statistical regularities, it is often possible to accurately estimate the utilitarian social welfare function, even if we only have very noisy data about individual utility functions and interpersonal utility comparisons. In particular, we show that it is often possible to identify an optimal or close-to-optimal utilitarian social choice using voting rules such as the Borda rule, approval voting, relative utilitarianism, or any Condorcet-consistent rule.

Background: A long-standing epidemiological puzzle is the reduced rate of rheumatoid arthritis (RA) in those with schizophrenia (SZ) and vice versa. Traditional epidemiological approaches to determine if this negative association is underpinned by genetic factors would test for reduced rates of one disorder in relatives of the other, but sufficiently powered data sets are difficult to achieve. The genomics era presents an alternative paradigm for investigating the genetic relationship between two uncommon disorders. Methods: We use genome-wide common single nucleotide polymorphism (SNP) data from independently collected SZ and RA case-control cohorts to estimate the SNP correlation between the disorders. We test a genotype X environment (GxE) hypothesis for SZ with environment defined as winter- vs summer-born. Results: We estimate a small but significant negative SNP-genetic correlation between SZ and RA (−0.046, s.e. 0.026, P = 0.036). The negative correlation was stronger for the SNP set attributed to coding or regulatory regions (−0.174, s.e. 0.071, P = 0.0075). Our analyses led us to hypothesize a gene-environment interaction for SZ in the form of immune challenge. We used month of birth as a proxy for environmental immune challenge and estimated the genetic correlation between winter-born and non-winter born SZ to be significantly less than 1 for coding/regulatory region SNPs (0.56, s.e. 0.14, P = 0.00090). Conclusions: Our results are consistent with epidemiological observations of a negative relationship between SZ and RA reflecting, at least in part, genetic factors. Results of the month of birth analysis are consistent with pleiotropic effects of genetic variants dependent on environmental context. Refereed/Peer-reviewed

What are the psychological consequences of the increasingly politicized nature of the COVID-19 pandemic in the United States relative to similar Western countries? In a two-wave study completed early (March) and later (December) in the pandemic, we found that polarization was greater in the United States ( N = 1,339) than in Canada ( N = 644) and the United Kingdom. ( N = 1,283). Political conservatism in the United States was strongly associated with engaging in weaker mitigation behaviors, lower COVID-19 risk perceptions, greater misperceptions, and stronger vaccination hesitancy. Although there was some evidence that cognitive sophistication was associated with increased polarization in the United States in December (but not March), cognitive sophistication was nonetheless consistently negatively correlated with misperceptions and vaccination hesitancy across time, countries, and party lines. Furthermore, COVID-19 skepticism in the United States was strongly correlated with distrust in liberal-leaning mainstream news outlets and trust in conservative-leaning news outlets, suggesting that polarization may be driven by differences in information environments.

En el marco de una reflexión de orden general sobre el principio de las responsabilidades comunes pero diferenciadas, la presente contribución plantea la cuestión de la presencia de este principio en el campo del derecho internacional de las aguas dulces. La respuesta a esta pregunta es afirmativa, aunque debe ser matizada. El principio de responsabilidades comunes pero diferenciadas aparece raramente en esta especialidad, aunque su aplicación plantea ventajas principalmente en dos casos : en situaciones en las cuales los estados ribereños de un mismo curso de agua internacional/acuífero transfronterizo no presentan el mismo nivel de desarrollo, y cuando la gestión de los recursos acuáticos se extiende mas allá del marco geográfico de la cuenca hidrográfica/acuífera. Dans le contexte d’une réflexion générale menée sur le principe des responsabilités communes mais différenciées (PRCMD), l’auteur s’interroge sur la présence de ce principe dans le domaine du droit international des eaux douces. Sa réponse est affirmative mais nuancée. Le recours au PRCMD, qui reste exceptionnel dans cette spécialité, se fait utilement dans deux cas de figure : dans des situations où les États riverains du même cours d’eau international/aquifère transfrontière ne présentent pas un degré de développement identique et lorsque la gestion des ressources en eau dépasse le cadre géographique du bassin hydrographique/aquifère. This paper discusses the relevance and impact of the principle of Common But Differentiated Responsibilities (CBDR) in the specific field of international fresh water law. The CBDR principle applies to a certain extent in a field where traditionally there is no place for it. This occurs mainly in two situations : first, when riparian States along the same international watercourse/transboundary aquifer do not have the same level of development ; and second, when the management of water resources extends beyond the geographical area of the river basin/aquifer.

The effect of blocky to lamellar phase transformation on the microstructure and micro-texture of a Magnesium-Rare earth alloy containing long-period stacking order (LPSO) phases were examined comprehensively at the isothermal temperature of 400 °C via multiaxial forging. A very fine-grained microstructure with an average grain size of 1 μm was achieved after applying three multi-axial forging (MAF) passes. Particle stimulated nucleation (PSN) along with continuous dynamic recrystallizations (CDRX) due to the blocky LPSO phases were realized to be the main reasons for the achievement of such fine microstructure. The deformation-induced blocky to lamellar phase transformation began at 1/3 pass and expanded through the whole microstructure after the third pass. Such phase transformation was found to be initiated by the fragmentation of blocky phases. As a result of PSN and CDRX mechanisms, two new rare earth (RE) texture components of and || Transverse Direction (TD) were formed at the second MAF pass that led to a highly randomized deformation texture. Nevertheless, the continuous breakdown of blocky phases and their subsequent phase transformation to lamellar LPSO suppressed PSN at the third deformation pass. Hence, the formed RE texture components were disappeared which in turn increased the texture intensity at this deformation pass.

Author(s): Lochmuller, Hanns; Behin, Anthony; Tournev, Ivailo; Tarnopolsky, Mark; Horvath, Rita; Pogoryelova, Oksana; Shah, Jinay; Koutsoukos, Tony; Skrinar, Alison; Kakkis, Emil; Bedrosian, Camille L; Mozaffar, Tahseen | Abstract: BackgroundGNE myopathy is a rare, autosomal recessive, muscle disease caused by mutations in GNE and is characterized by rimmed vacuoles on muscle biopsy and progressive distal to proximal muscle weakness.ObjectiveInvestigate the clinical presentation and progression of GNE myopathy.MethodsThe GNE Myopathy Disease Monitoring Program was an international, prospective, observational study in subjects with GNE myopathy. Muscle strength was assessed with hand-held dynamometry (HHD), with upper extremity (UE) and lower extremity (LE) composite scores reflecting upper and lower extremity muscle groups, respectively. The GNE myopathy-Functional Activity Scale (GNEM-FAS) was used to further assess impairment in mobility, upper extremity function, and self-care.ResultsEighty-seven of 101 enrolled subjects completed the trial until study closure by the sponsor; 60 completed 36 months. Mean (SD) HHD UE composite score decreased from 34.3 kg (32.0) at baseline to 29.4 kg (32.6) kg at month 36 (LS mean change [95%CI]: -3.8 kg [-5.9, -1.7]; P = 0.0005). Mean (SD) HHD LE composite score decreased from 32.0 kg (34.1) at baseline to 25.5 kg (31.2) at month 36 (LS mean change [95%CI]: -4.9 [-7.7, -2.2]; P = 0.0005). GNEM-FAS scores were more severe at baseline in subjects who walked l200 meters versus ≥200 meters in 6 minutes; in both groups, GNEM-FAS total, mobility, UE, and self-care scores decreased from baseline through month 36.ConclusionsThese findings demonstrate progressive decline in muscle strength in GNE myopathy and provide insight into the appropriate tools to detect clinically meaningful changes in future GNE myopathy interventional trials.