Consensus‐based technical recommendations for clinical translation of renal phase contrast MRI

Background Phase‐contrast (PC) MRI is a feasible and valid noninvasive technique to measure renal artery blood flow, showing potential to support diagnosis and monitoring of renal diseases. However, the variability in measured renal blood flow values across studies is large, most likely due to differences in PC‐MRI acquisition and processing. Standardized acquisition and processing protocols are therefore needed to minimize this variability and maximize the potential of renal PC‐MRI as a clinically useful tool. Purpose To build technical recommendations for the acquisition, processing, and analysis of renal 2D PC‐MRI data in human subjects to promote standardization of renal blood flow measurements and facilitate the comparability of results across scanners and in multicenter clinical studies. Study Type Systematic consensus process using a modified Delphi method. Population Not applicable. Sequence Field/Strength Renal fast gradient echo‐based 2D PC‐MRI. Assessment An international panel of 27 experts from Europe, the USA, Australia, and Japan with 6 (interquartile range 4–10) years of experience in 2D PC‐MRI formulated consensus statements on renal 2D PC‐MRI in two rounds of surveys. Starting from a recently published systematic review article, literature‐based and data‐driven statements regarding patient preparation, hardware, acquisition protocol, analysis steps, and data reporting were formulated. Statistical Tests Consensus was defined as ≥75% unanimity in response, and a clear preference was defined as 60–74% agreement among the experts. Results Among 60 statements, 57 (95%) achieved consensus after the second‐round survey, while the remaining three showed a clear preference. Consensus statements resulted in specific recommendations for subject preparation, 2D renal PC‐MRI data acquisition, processing, and reporting. Data Conclusion These recommendations might promote a widespread adoption of renal PC‐MRI, and may help foster the set‐up of multicenter studies aimed at defining reference values and building larger and more definitive evidence, and will facilitate clinical translation of PC‐MRI. Level of Evidence 1 Technical Efficacy Stage

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Nuevos registros de Braquiópodos y consideraciones sobre las faunas de Tivertoniastreptorhynchus (Moscoviano) y Costatumulus amosi (Pérmico temprano) del oeste argentino: reexamen de las secciones clave de las Quebradas Agua del Jagüel y Santa Elena

The brachiopod Coolkilella aredesi sp. nov. and Calytrixia piersoni sp. nov. are proposed on the basis of specimens from the Del Salto, Río del Peñón and Agua del Jagüel formations. Their biostratigraphic implications are discussed together with new records of Septosyringothyris (Precosyringothyris) jaguelensis Lech and Streptorhynchus inaequiornatus Leanza at the top of the latter unit. The stratigraphic record, paleontological content and age of both the Tivertonia-Streptorhynchus assemblage (Moscovian) and the younger Costatumulus amosi fauna (Sakmarian–Artinskian) were reviewed and assessed based on outcrops at Quebrada Agua del Jagüel and Quebrada Santa Elena. Faunal content confirms the most recent stratigraphic, biostratigraphic and paleoclimatic frameworks. These a diachronic nature of the Agua del Jagüel and Cordón del Jagüel formations, supporting the absence of an early Permian glacial event in western Argentina.Se proponen las nuevas especies de braquiópodos Coolkilella aredesi sp. nov. y Calytrixia piersoni sp. nov. sobre la base de especímenes provenientes de las formaciones Del Salto, Río del Peñón y Agua del Jagüel. Se analizan sus implicancias bioestratigraficas junto al significado de nuevos registros de Septosyringothyris (Precosyringothyris) jaguelensis Lech y Streptorhynchus inaequiornatus Leanza en el techo de la última unidad mencionada. Se revisan y precisan el registro estratigráfico, contenido paleontológico y edades de la asociación de Tivertonia-Streptorhynchus (Moscoviano) y de la fauna más joven de Costatumulus amosi (Sakmariano—Artinskiano) en los afloramientos de las Quebradas de Agua de Jagüel y Santa Elena. El contenido faunístico permite corroborar los más recientes esquemas estratigráficos, bioestratigráficos y paleoclimáticos, reconociendo las formaciones Agua del Jagüel y Cordón del Jagüel como unidades diacrónicas y desestimando a su vez la existencia de un evento glacial Pérmico en el oeste de Argentina.Fil: Taboada, Arturo Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de la Patagonia "San Juan Bosco". Facultad de Ciencias Naturales - Sede Esquel. Laboratorio de Investigaciones en Evolución y Biodiversidad; Argentin

Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis

BACKGROUND: Findings from family and twin studies suggest that genetic contributions to psychiatric disorders do not in all cases map to present diagnostic categories. We aimed to identify specific variants underlying genetic effects shared between the five disorders in the Psychiatric Genomics Consortium: autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia. METHODS: We analysed genome-wide single-nucleotide polymorphism (SNP) data for the five disorders in 33,332 cases and 27,888 controls of European ancestory. To characterise allelic effects on each disorder, we applied a multinomial logistic regression procedure with model selection to identify the best-fitting model of relations between genotype and phenotype. We examined cross-disorder effects of genome-wide significant loci previously identified for bipolar disorder and schizophrenia, and used polygenic risk-score analysis to examine such effects from a broader set of common variants. We undertook pathway analyses to establish the biological associations underlying genetic overlap for the five disorders. We used enrichment analysis of expression quantitative trait loci (eQTL) data to assess whether SNPs with cross-disorder association were enriched for regulatory SNPs in post-mortem brain-tissue samples. FINDINGS: SNPs at four loci surpassed the cutoff for genome-wide significance (p<5×10(-8)) in the primary analysis: regions on chromosomes 3p21 and 10q24, and SNPs within two L-type voltage-gated calcium channel subunits, CACNA1C and CACNB2. Model selection analysis supported effects of these loci for several disorders. Loci previously associated with bipolar disorder or schizophrenia had variable diagnostic specificity. Polygenic risk scores showed cross-disorder associations, notably between adult-onset disorders. Pathway analysis supported a role for calcium channel signalling genes for all five disorders. Finally, SNPs with evidence of cross-disorder association were enriched for brain eQTL markers. INTERPRETATION: Our findings show that specific SNPs are associated with a range of psychiatric disorders of childhood onset or adult onset. In particular, variation in calcium-channel activity genes seems to have pleiotropic effects on psychopathology. These results provide evidence relevant to the goal of moving beyond descriptive syndromes in psychiatry, and towards a nosology informed by disease cause. FUNDING: National Institute of Mental Health