An algorithmic approach to resolutions

We provide an algorithmic method for constructing projective resolutions of modules over quotients of path algebras. This algorithm is modified to construct minimal projective resolutions of linear modules over Koszul algebras

Resolutions and cohomology over complete intersections

This chapter contains a new proof and new applications of a theorem of Shamash and Eisenbud, providing a construction of projective resolutions of modules over a complete intersection. The duals of these infinite projective resolutions are finitely generated differential graded modules over a graded polynomial ring, so they can be represented in the computer, and can be used to compute Ext modules simultaneously in all homological degrees. It is shown how to write Macaulay 2 code to implement the construction, and how to use the computer to determine invariants of modules over complete intersections that are difficult to obtain otherwise

Identification of Novel CYP2D7-2D6 Hybrids: Non-Functional and Functional Variants

Polymorphic expression of CYP2D6 contributes to the wide range of activity observed for this clinically important drug metabolizing enzyme. In this report we describe novel CYP2D7/2D6 hybrid genes encoding non-functional and functional CYP2D6 protein and a CYP2D7 variant that mimics a CYP2D7/2D6 hybrid gene. Five-kilobyte-long PCR products encompassing the novel genes were entirely sequenced. A quantitative assay probing in different gene regions was employed to determine CYP2D6 and 2D7 copy number variations and the relative position of the hybrid genes within the locus was assessed by long-range PCR. In addition to the previously known CYP2D6*13 and *66 hybrids, we describe three novel non-functional CYP2D7-2D6 hybrids with gene switching in exon 2 (CYP2D6*79), intron 2 (CYP2D6*80), and intron 5 (CYP2D6*67). A CYP2D7-specific T-ins in exon 1 causes a detrimental frame shift. One subject revealed a CYP2D7 conversion in the 5′-flanking region of a CYP2D6*35 allele, was otherwise unaffected (designated CYP2D6*35B). Finally, three DNAs revealed a CYP2D7 gene with a CYP2D6-like region downstream of exon 9 (designated CYP2D7[REP6]). Quantitative copy number determination, sequence analyses, and long-range PCR mapping were in agreement and excluded the presence of additional gene units. Undetected hybrid genes may cause over-estimation of CYP2D6 activity (CYP2D6*1/*1 vs *1/hybrid, etc), but may also cause results that may interfere with the genotype determination. Detection of hybrid events, “single” and tandem, will contribute to more accurate phenotype prediction from genotype data

Localisation des activités métropolitaines : quels impacts sur le navettage à montréal?

Le phénomène de déconcentration urbaine constitue une réalité à laquelle de nombreuses métropoles doivent désormais faire face. Perturbant les modèles de localisation des activités à l’échelle métropolitaine, ce processus n’est pas sans bouleverser de nombreux paradigmes, notamment en ce qui a trait aux dynamiques de mobilité. Bien que le lien entre forme urbaine et navettage ait fait l’objet de nombreuses études, les enjeux de cette réorganisation spatiale demeurent mal connus, leurs résultats étant souvent contradictoires. Parallèlement, les préoccupations environnementales grandissantes des métropoles se traduisent par une multiplication des inventaires, plans et politiques visant à réduire leurs émissions de GES. Ainsi, quels impacts la localisation des activités métropolitaines, sous l’influence du phénomène de déconcentration des activités, peut-elle avoir sur le navettage métropolitain et, par conséquent, sur les émissions de GES reliées au transport? À Montréal, le secteur des transports s’avère effectivement crucial en termes de réduction des émissions de GES, ce qui fournit un cadre d’étude particulièrement intéressant pour répondre à cette question.A number of metropolitan areas are confronted with the process of urban diffusion. Under such circumstances, metropolitan-wide urban activity location models are disrupted by this process and pose a challenge to a range of paradigms, particularly those that address the dynamics of mobility. Although a vast literature exists on the relationship between urban form and commuting, the issues that surround spatial reorganization are not clearly defined, and research findings contradict each other. At the same time, metropolitan environmental awareness is growing, leading to greenhouse gas emission inventories, climate change plans and policies to reduce metropolitan emissions. The question on the implications of the diffusion of activities at the metropolitan level on commuting patterns and thus on transportation greenhouse gas emissions can be raised. This paper offers new insights into this question by examining how the transportation sector can play a vital role in Montréal in contributing to the reduction of GHGs

Pharmacogenomics of the efficacy and safety of Colchicine in COLCOT

© 2021 The Authors. Circulation: Genomic and Precision Medicine is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited and is not used for commercial purposes.Background: The randomized, placebo-controlled COLCOT (Colchicine Cardiovascular Outcomes Trial) has shown the benefits of colchicine 0.5 mg daily to lower the rate of ischemic cardiovascular events in patients with a recent myocardial infarction. Here, we conducted a post hoc pharmacogenomic study of COLCOT with the aim to identify genetic predictors of the efficacy and safety of treatment with colchicine. Methods: There were 1522 participants of European ancestry from the COLCOT trial available for the pharmacogenomic study of COLCOT trial. The pharmacogenomic study's primary cardiovascular end point was defined as for the main trial, as time to first occurrence of cardiovascular death, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina requiring coronary revascularization. The safety end point was time to the first report of gastrointestinal events. Patients' DNA was genotyped using the Illumina Global Screening array followed by imputation. We performed a genome-wide association study in colchicine-treated patients. Results: None of the genetic variants passed the genome-wide association study significance threshold for the primary cardiovascular end point conducted in 702 patients in the colchicine arm who were compliant to medication. The genome-wide association study for gastrointestinal events was conducted in all 767 patients in the colchicine arm and found 2 significant association signals, one with lead variant rs6916345 (hazard ratio, 1.89 [95% CI, 1.52-2.35], P=7.41×10-9) in a locus which colocalizes with Crohn disease, and one with lead variant rs74795203 (hazard ratio, 2.51 [95% CI, 1.82-3.47]; P=2.70×10-8), an intronic variant in gene SEPHS1. The interaction terms between the genetic variants and treatment with colchicine versus placebo were significant. Conclusions: We found 2 genomic regions associated with gastrointestinal events in patients treated with colchicine. Those findings will benefit from replication to confirm that some patients may have genetic predispositions to lower tolerability of treatment with colchicine.info:eu-repo/semantics/publishedVersio

Enriching news events with meta-knowledge information

Given the vast amounts of data available in digitised textual form, it is important to provide mechanisms that allow users to extract nuggets of relevant information from the ever growing volumes of potentially important documents. Text mining techniques can help, through their ability to automatically extract relevant event descriptions, which link entities with situations described in the text. However, correct and complete interpretation of these event descriptions is not possible without considering additional contextual information often present within the surrounding text. This information, which we refer to as meta-knowledge, can include (but is not restricted to) the modality, subjectivity, source, polarity and specificity of the event. We have developed a meta-knowledge annotation scheme specifically tailored for news events, which includes six aspects of event interpretation. We have applied this annotation scheme to the ACE 2005 corpus, which contains 599 documents from various written and spoken news sources. We have also identified and annotated the words and phrases evoking the different types of meta-knowledge. Evaluation of the annotated corpus shows high levels of inter-annotator agreement for five meta-knowledge attributes, and moderate level of agreement for the sixth attribute. Detailed analysis of the annotated corpus has revealed further insights into the expression mechanisms of different types of meta-knowledge, their relative frequencies and mutual correlations

Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries

Funding Information: M.B.A. holds a Tier 2 Canada Research Chair in the Developmental Origins of Chronic Disease at the University of Manitoba and is a Fellow in the Canadian Institutes for Advanced Research (CIFAR) Humans and the Microbiome Program. Her effort on this project was partly supported by HDR UK and ICODA. K.K.C.M. declares support from The Innovation and Technology Commission of the Hong Kong Special Administrative Region Government, and Hong Kong Research Grants Council Collaborative Research Fund Coronavirus Disease (COVID-19) and Novel Infectious Disease Research Exercise (Ref: C7154-20G) and grants from C W Maplethorpe Fellowship, National Institute of Health Research UK, European Commission Framework Horizon 2020 and has consulted for IQVIA Ltd. A.S. is supported by ICODA and HDR UK, and has received a research grant from HDR UK to the BREATHE Hub. He participates on the Scottish and UK Government COVID-19 Advisory Committees, unremunerated. S.J.S. is supported by a Wellcome Trust Clinical Career Development Fellowship (209560/Z/17/Z) and HDR UK, and has received personal fees from Hologic and Natera outside the submitted work. D.B. is supported by a National Health and Medical Research Council (Australia) Investigator Grant (GTN1175744). I.C.K.W. declares support from The Innovation and Technology Commission of the Hong Kong Special Administrative Region Government, and Hong Kong Research Grants Council Collaborative Research Fund Coronavirus Disease (COVID-19) and Novel Infectious Disease Research Exercise (Ref: C7154-20G), and grants from Hong Kong Research Grant Council, National Institute of Health Research UK, and European Commission Framework Horizon 2020. H.Z. is supported by a UNSW Scientia Program Award and reports grants from European Commission Framework Horizon 2020, Icelandic Centre for Research, and Australia’s National Health and Medical Research Council. H.Z. was an employee of the UNSW Centre for Big Data Research in Health, which received funding from AbbVie Australia to conduct research, unrelated to the current study. I.I.A.A., C.D.A., K.A., A.I.A., L.C., S.S., G.E.-G., O.W.G., L. Huicho, S.H., A.K., K.L., V.N., I.P., N.R.R., T.R., T.A.H.R., V.L.S., E.M.S., L.T., R.W. and H.Z. received funding from HDRUK (grant #2020.106) to support data collection for the iPOP study. K.H., R.B., S.O.E., A.R.-P. and J.H. receive salary from ICODA. M.B. received trainee funding from HDRUK (grant #2020.106). J.E.M. received trainee funding from HDRUK (grant #2020.109). Other relevant funding awarded to authors to conduct research for iPOP include: M.G. received funding from THL, Finnish Institute for Health and Welfare to support data collection. K.D. received funding from EDCTP RIA2019 and HDRUK (grant #2020.106) to support data collection. R.B. received funding from Alzheimer’s Disease Data Initiative and ICODA for the development of federated analysis. A.D.M. received funding from HDR UK who receives its funding from the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation (BHF) and the Wellcome Trust; and Administrative Data Research UK, which is funded by the Economic and Social Research Council (grant ES/S007393/1). N.A. received funding from the National Institutes of Health (R35GM138353). O.S received funding from NordForsk (grant #105545). The remaining authors declare no competing interests. Funding Information: Funding and in-kind support: This work was supported by the International COVID-19 Data Alliance (ICODA), an initiative funded by the Bill and Melinda Gates Foundation and Minderoo as part of the COVID-19 Therapeutics Accelerator and convened by Health Data Research (HDR) UK, in addition to support from the HDR UK BREATHE Hub. Several ICODA partners contributed to the study, including: Cytel (statistical support), the Odd Group (data visualization) and Aridhia Informatics (development of federated analysis using a standardized protocol ([Common API] https://github.com/federated-data-sharing/ ) to be used in future work). Additional contributors: We acknowledge the important contributions from the following individuals: A. C. Hennemann and D. Suguitani (patient partners from Prematuridade: Brazilian Parents of Preemies’ Association, Porto Alegre, Brazil); N. Postlethwaite (implementation of processes supporting the trustworthy collection, governance and analysis of data from ICODA, HDR UK, London, UK); A. S. Babatunde (led data acquisition from University of Uyo Teaching Hospital, Uyo, Nigeria); N. Silva (data quality, revision and visualization assessment from Methods, Analytics and Technology for Health (M.A.T.H) Consortium, Belo Horizonte, Brazil); J. Söderling (data management from the Karolinska Institutet, Stockholm, Sweden). We also acknowledge the following individuals who assisted with data collection efforts: R. Goemaes (Study Centre for Perinatal Epidemiology (SPE), Brussels, Belgium); C. Leroy (Le Centre d'Épidémiologie Périnatale (CEpiP), Brussels, Belgium); J. Gamba and K. Ronald (St. Francis Nsambya Hospital, Kampala, Uganda); M. Heidarzadeh (Tabriz Medical University, Tabriz, Iran); M. J. Ojeda (Pontificia Universidad Católica de Chile, Santiago, Chile); S. Nangia (Lady Hardinge Medical College, New Delhi, India); C. Nelson, S. Metcalfe and W. Luo (Maternal Infant Health Section of the Public Health Agency of Canada, Ottawa, Canada); K. Sitcov (Foundation for Health Care Quality, Seattle, United States); A. Valek (Semmelweis University, Budapest, Hungary); M. R. Yanlin Liu (Mater Data and Analytics, Brisbane, Australia). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Funding Information: Funding and in-kind support: This work was supported by the International COVID-19 Data Alliance (ICODA), an initiative funded by the Bill and Melinda Gates Foundation and Minderoo as part of the COVID-19 Therapeutics Accelerator and convened by Health Data Research (HDR) UK, in addition to support from the HDR UK BREATHE Hub. Several ICODA partners contributed to the study, including: Cytel (statistical support), the Odd Group (data visualization) and Aridhia Informatics (development of federated analysis using a standardized protocol ([Common API] https://github.com/federated-data-sharing/) to be used in future work). Additional contributors: We acknowledge the important contributions from the following individuals: A. C. Hennemann and D. Suguitani (patient partners from Prematuridade: Brazilian Parents of Preemies’ Association, Porto Alegre, Brazil); N. Postlethwaite (implementation of processes supporting the trustworthy collection, governance and analysis of data from ICODA, HDR UK, London, UK); A. S. Babatunde (led data acquisition from University of Uyo Teaching Hospital, Uyo, Nigeria); N. Silva (data quality, revision and visualization assessment from Methods, Analytics and Technology for Health (M.A.T.H) Consortium, Belo Horizonte, Brazil); J. Söderling (data management from the Karolinska Institutet, Stockholm, Sweden). We also acknowledge the following individuals who assisted with data collection efforts: R. Goemaes (Study Centre for Perinatal Epidemiology (SPE), Brussels, Belgium); C. Leroy (Le Centre d'Épidémiologie Périnatale (CEpiP), Brussels, Belgium); J. Gamba and K. Ronald (St. Francis Nsambya Hospital, Kampala, Uganda); M. Heidarzadeh (Tabriz Medical University, Tabriz, Iran); M. J. Ojeda (Pontificia Universidad Católica de Chile, Santiago, Chile); S. Nangia (Lady Hardinge Medical College, New Delhi, India); C. Nelson, S. Metcalfe and W. Luo (Maternal Infant Health Section of the Public Health Agency of Canada, Ottawa, Canada); K. Sitcov (Foundation for Health Care Quality, Seattle, United States); A. Valek (Semmelweis University, Budapest, Hungary); M. R. Yanlin Liu (Mater Data and Analytics, Brisbane, Australia). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Publisher Copyright: © 2023, The Author(s).Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from −90% to +30%, were reported in many countries following early COVID-19 pandemic response measures (‘lockdowns’). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95–0.98, P value <0.0001), second (0.96, 0.92–0.99, 0.03) and third (0.97, 0.94–1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96–1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88–1.14, 0.98), third (0.99, 0.88–1.12, 0.89) and fourth (1.01, 0.87–1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02–1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03–1.15, 0.002), third (1.10, 1.03–1.17, 0.003) and fourth (1.12, 1.05–1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways.Peer reviewe

Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries.

Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways