Green Infrastructure Design Influences Communities of Urban Soil Bacteria

The importance of natural ecosystem processes is often overlooked in urban areas. Green Infrastructure (GI) features have been constructed in urban areas as elements to capture and treat excess urban runoff while providing a range of ancillary benefits, e.g., ecosystem processes mediated by microorganisms that improve air and water quality, in addition to the associations with plant and tree rhizospheres. The objective of this study was to characterize the bacterial community and diversity in engineered soils (Technosols) of five types of GI in New York City; vegetated swales, right of way bioswales (ROWB; including street-side infiltration systems and enhanced tree pits), and an urban forest. The design of ROWB GI features directly connects with the road to manage street runoff, which can increase the Technosol saturation and exposure to urban contaminants washed from the street and carried into the GI feature. This GI design specifically accommodates dramatic pulses of water that influence the bacterial community composition and diversity through the selective pressure of contaminants or by disturbance. The ROWB had the highest biodiversity, but no significant correlation with levels of soil organic matter and microbially-mediated biogeochemical functions. Another important biogeochemical parameter for soil bacterial communities is pH, which influenced the bacterial community composition, consistent with studies in non-urban soils. Bacterial community composition in GI features showed signs of anthropogenic disturbance, including exposure to animal feces and chemical contaminants, such as petroleum products. Results suggest the overall design and management of GI features with a channeled connection with street runoff, such as ROWB, have a comprehensive effect on soil parameters (particularly organic matter) and the bacterial community. One key consideration for future assessments of GI microbial community would be to determine the source of organic matter and elucidate the relationship between vegetation, Technosol, and bacteria in the designed GI features

Genetic variability in sporadic amyotrophic lateral sclerosis

With the advent of gene therapies for amyotrophic lateral sclerosis (ALS), there is a surge in gene testing for this disease. Although there is ample experience with gene testing for C9orf72, SOD1, FUS and TARDBP in familial ALS, large studies exploring genetic variation in all ALS-associated genes in sporadic ALS (sALS) are still scarce. Gene testing in a diagnostic setting is challenging, given the complex genetic architecture of sALS, for which there are genetic variants with large and small effect sizes. Guidelines for the interpretation of genetic variants in gene panels and for counselling of patients are lacking. We aimed to provide a thorough characterization of genetic variability in ALS genes by applying the American College of Medical Genetics and Genomics (ACMG) criteria on whole genome sequencing data from a large cohort of 6013 sporadic ALS patients and 2411 matched controls from Project MinE. We studied genetic variation in 90 ALS-associated genes and applied customized ACMG-criteria to identify pathogenic and likely pathogenic variants. Variants of unknown significance were collected as well. In addition, we determined the length of repeat expansions in C9orf72, ATXN1, ATXN2 and NIPA1 using the ExpansionHunter tool. We found C9orf72 repeat expansions in 5.21% of sALS patients. In 50 ALS-associated genes, we did not identify any pathogenic or likely pathogenic variants. In 5.89%, a pathogenic or likely pathogenic variant was found, most commonly in SOD1, TARDBP, FUS, NEK1, OPTN or TBK1. Significantly more cases carried at least one pathogenic or likely pathogenic variant compared to controls (odds ratio 1.75; P-value 1.64 × 10-5). Isolated risk factors in ATXN1, ATXN2, NIPA1 and/or UNC13A were detected in 17.33% of cases. In 71.83%, we did not find any genetic clues. A combination of variants was found in 2.88%. This study provides an inventory of pathogenic and likely pathogenic genetic variation in a large cohort of sALS patients. Overall, we identified pathogenic and likely pathogenic variants in 11.13% of ALS patients in 38 known ALS genes. In line with the oligogenic hypothesis, we found significantly more combinations of variants in cases compared to controls. Many variants of unknown significance may contribute to ALS risk, but diagnostic algorithms to reliably identify and weigh them are lacking. This work can serve as a resource for counselling and for the assembly of gene panels for ALS. Further characterization of the genetic architecture of sALS is necessary given the growing interest in gene testing in ALS

A Standard Set of Value-Based Patient-Centered Outcomes for Breast Cancer: The International Consortium for Health Outcomes Measurement (ICHOM) Initiative.

A major challenge in value-based health care is the lack of standardized health outcomes measurements, hindering optimal monitoring and comparison of the quality of health care across different settings globally. The International Consortium for Health Outcomes Measurement (ICHOM) assembled a multidisciplinary international working group, comprised of 26 health care providers and patient advocates, to develop a standard set of value-based patient-centered outcomes for breast cancer (BC). The working group convened via 8 teleconferences and completed a follow-up survey after each meeting. A modified 2-round Delphi method was used to achieve consensus on the outcomes and case-mix variables to be included. Patient focus group meetings (8 early or metastatic BC patients) and online anonymized surveys of 1225 multinational BC patients and survivors were also conducted to obtain patients' input. The standard set encompasses survival and cancer control, and disutility of care (eg, acute treatment complications) outcomes, to be collected through administrative data and/or clinical records. A combination of multiple patient-reported outcomes measurement (PROM) tools is recommended to capture long-term degree of health outcomes. Selected case-mix factors were recommended to be collected at baseline. The ICHOM will endeavor to achieve wide buy-in of this set and facilitate its implementation in routine clinical practice in various settings and institutions worldwide

The Next Generation Virgo Cluster Survey

International audienceThe Next Generation Virgo Cluster Survey (NGVS) is a CFHT MegaPrime large program to survey the Virgo Cluster from its core to virial radius, for a total coverage of 104 square degrees. Over the next four years, the survey will perform deep imaging (10 sigma detection for point sources of 25.7 mag in the g-band) in five band-passes (u*,g',r',i',z'), thereby superceding all optical studies of this uniquely important system. The program's main scientific objectives are: the characterization of the faint-end shape of the galaxy luminosity function, the characterization of galaxy scaling relations over a factor 10<SUP>7</SUP> in mass, the cluster/intracluster medium/galaxy connection, the role of environmental effects in galaxy evolution,and the fossil record of star formation and chemical enrichment in dense environments. Numerous ancillary projects - from a survey of the Galactic halo to a cosmic shear measurement of the matter power spectrum on large scales - will also be enabled. Details about the survey can be found at http://astrowww.phys.uvic.ca/ lff/NGVS.htm

The Next Generation Virgo Cluster Survey

International audienceThe Next Generation Virgo Cluster Survey (NGVS) is a CFHT MegaPrime large program to survey the Virgo Cluster from its core to virial radius, for a total coverage of 104 square degrees. Over the next four years, the survey will perform deep imaging (10 sigma detection for point sources of 25.7 mag in the g-band) in five band-passes (u*,g',r',i',z'), thereby superceding all optical studies of this uniquely important system. The program's main scientific objectives are: the characterization of the faint-end shape of the galaxy luminosity function, the characterization of galaxy scaling relations over a factor 10<SUP>7</SUP> in mass, the cluster/intracluster medium/galaxy connection, the role of environmental effects in galaxy evolution,and the fossil record of star formation and chemical enrichment in dense environments. Numerous ancillary projects - from a survey of the Galactic halo to a cosmic shear measurement of the matter power spectrum on large scales - will also be enabled. Details about the survey can be found at http://astrowww.phys.uvic.ca/ lff/NGVS.htm

The Next Generation Virgo Cluster Survey

International audienceThe Next Generation Virgo Cluster Survey (NGVS) is a CFHT MegaPrime large program to survey the Virgo Cluster from its core to virial radius, for a total coverage of 104 square degrees. Over the next four years, the survey will perform deep imaging (10 sigma detection for point sources of 25.7 mag in the g-band) in five band-passes (u*,g',r',i',z'), thereby superceding all optical studies of this uniquely important system. The program's main scientific objectives are: the characterization of the faint-end shape of the galaxy luminosity function, the characterization of galaxy scaling relations over a factor 10<SUP>7</SUP> in mass, the cluster/intracluster medium/galaxy connection, the role of environmental effects in galaxy evolution,and the fossil record of star formation and chemical enrichment in dense environments. Numerous ancillary projects - from a survey of the Galactic halo to a cosmic shear measurement of the matter power spectrum on large scales - will also be enabled. Details about the survey can be found at http://astrowww.phys.uvic.ca/ lff/NGVS.htm

The Next Generation Virgo Cluster Survey

International audienceThe Next Generation Virgo Cluster Survey (NGVS) is a CFHT MegaPrime large program to survey the Virgo Cluster from its core to virial radius, for a total coverage of 104 square degrees. Over the next four years, the survey will perform deep imaging (10 sigma detection for point sources of 25.7 mag in the g-band) in five band-passes (u*,g',r',i',z'), thereby superceding all optical studies of this uniquely important system. The program's main scientific objectives are: the characterization of the faint-end shape of the galaxy luminosity function, the characterization of galaxy scaling relations over a factor 10<SUP>7</SUP> in mass, the cluster/intracluster medium/galaxy connection, the role of environmental effects in galaxy evolution,and the fossil record of star formation and chemical enrichment in dense environments. Numerous ancillary projects - from a survey of the Galactic halo to a cosmic shear measurement of the matter power spectrum on large scales - will also be enabled. Details about the survey can be found at http://astrowww.phys.uvic.ca/ lff/NGVS.htm

The Effect of SMN Gene Dosage on ALS Risk and Disease Severity

Objective: The role of the survival of motor neuron (SMN) gene in amyotrophic lateral sclerosis (ALS) is unclear, with several conflicting reports. A decisive result on this topic is needed, given that treatment options are available now for SMN deficiency. Methods: In this largest multicenter case control study to evaluate the effect of SMN1 and SMN2 copy numbers in ALS, we used whole genome sequencing data from Project MinE data freeze 2. SMN copy numbers of 6,375 patients with ALS and 2,412 controls were called from whole genome sequencing data, and the reliability of the calls was tested with multiplex ligation-dependent probe amplification data. Results: The copy number distribution of SMN1 and SMN2 between cases and controls did not show any statistical differences (binomial multivariate logistic regression SMN1 p = 0.54 and SMN2 p = 0.49). In addition, the copy number of SMN did not associate with patient survival (Royston-Parmar; SMN1 p = 0.78 and SMN2 p = 0.23) or age at onset (Royston-Parmar; SMN1 p = 0.75 and SMN2 p = 0.63). Interpretation: In our well-powered study, there was no association of SMN1 or SMN2 copy numbers with the risk of ALS or ALS disease severity. This suggests that changing SMN protein levels in the physiological range may not modify ALS disease course. This is an important finding in the light of emerging therapies targeted at SMN deficiencies

Genetic variability in sporadic amyotrophic lateral sclerosis

With the advent of gene therapies for amyotrophic lateral sclerosis (ALS), there is a surge in gene testing for this disease. Although there is ample experience with gene testing for C9orf72, SOD1, FUS and TARDBP in familial ALS, large studies exploring genetic variation in all ALS-associated genes in sporadic ALS (sALS) are still scarce. Gene testing in a diagnostic setting is challenging, given the complex genetic architecture of sALS, for which there are genetic variants with large and small effect sizes. Guidelines for the interpretation of genetic variants in gene panels and for counselling of patients are lacking. We aimed to provide a thorough characterization of genetic variability in ALS genes by applying the American College of Medical Genetics and Genomics (ACMG) criteria on whole genome sequencing data from a large cohort of 6013 sporadic ALS patients and 2411 matched controls from Project MinE. We studied genetic variation in 90 ALS-associated genes and applied customized ACMG-criteria to identify pathogenic and likely pathogenic variants. Variants of unknown significance were collected as well. In addition, we determined the length of repeat expansions in C9orf72, ATXN1, ATXN2 and NIPA1 using the ExpansionHunter tool. We found C9orf72 repeat expansions in 5.21% of sALS patients. In 50 ALS-associated genes, we did not identify any pathogenic or likely pathogenic variants. In 5.89%, a pathogenic or likely pathogenic variant was found, most commonly in SOD1, TARDBP, FUS, NEK1, OPTN or TBK1. Significantly more cases carried at least one pathogenic or likely pathogenic variant compared to controls (odds ratio 1.75; P-value 1.64 × 10-5). Isolated risk factors in ATXN1, ATXN2, NIPA1 and/or UNC13A were detected in 17.33% of cases. In 71.83%, we did not find any genetic clues. A combination of variants was found in 2.88%. This study provides an inventory of pathogenic and likely pathogenic genetic variation in a large cohort of sALS patients. Overall, we identified pathogenic and likely pathogenic variants in 11.13% of ALS patients in 38 known ALS genes. In line with the oligogenic hypothesis, we found significantly more combinations of variants in cases compared to controls. Many variants of unknown significance may contribute to ALS risk, but diagnostic algorithms to reliably identify and weigh them are lacking. This work can serve as a resource for counselling and for the assembly of gene panels for ALS. Further characterization of the genetic architecture of sALS is necessary given the growing interest in gene testing in ALS