Understanding the behaviour of (macro)chain transfer agents for RAFT controlled dispersion polymerisation in supercritical CO2

In this thesis, we focus on reversible addition- fragmentation chain transfer (RAFT) polymerisation in scCO2 with both molecular chain transfer agents (CTAs) (DDMAT, CPAB, CTPPA) and polydimethylsiloxane (PDMS)-based macromolecular CTAs (macro-CTAs) soluble in scCO2 (PDMS-DDMAT, PDMS-CPAB, PDMS-CTTPA), for the dispersion polymerisation of methyl methacrylate (MMA). Although the use of PDMS-DDMAT macro-CTAs led to stable PMMA particles, successful RAFT control was not attained, and part of the macro-CTA remained unreacted. Therefore, RAFT dispersion polymerisation of MMA in scCO2 was investigated using DDMAT and comparing to other molecular CTAs. Despite its low chain transfer constant (Ctr) towards MMA, DDMAT showed good control over PMMA molecular weight. A thorough investigation of the nucleation stage revealed an unexpected “in situ two-stage” mechanism that explains this result. Finally, a correlation between polymerisation control and the degree of solubility in scCO2 of the CTAs was stablished, giving rise to a guideline to select the best molecular CTA for MMA RAFT dispersion polymerisation in scCO2. The use of PDMS-CPAB and PDMS-CTPPA, which present chain-ends of high Ctr towards MMA, allowed an overall improvement of MMA polymerisation and RAFT control in scCO2 compared with PDMS-DDMAT. The good solubility of these macro-CTAs in scCO2 and the good control observed led to the formation of PDMS-b-PMMA block copolymers, suggesting the establishment of a polymerisation-induced self-assembly (PISA) process. This is a step forward towards PISA polymerisation via RAFT in scCO2 with fluorine-free macro-CTAs

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Understanding the behaviour of (macro)chain transfer agents for RAFT controlled dispersion polymerisation in supercritical CO2

Cette thèse porte sur l’utilisation de la polymérisation radicalaire contrôlée par transfert réversible par addition-fragmentation (RAFT) conduite dans le dioxyde de carbone supercritique (scCO2) avec des agents de transfert de chaîne moléculaires (CTA) (DDMAT, CPAB, CTPPA) ou macromoléculaires (macro-CTA) à base de polydimétylsiloxane (PDMS) (PDMS-DDMAT, PDMS-CPAB, PDMS-CTTPA), pour la polymérisation en dispersion du méthacrylate de méthyle (MMA). Bien que le PDMS-DDMAT ait pu stabiliser les particules de PMMA produites dans le scCO2, le contrôle de la polymérisation n'a pas été atteint et une partie du macro-CTA n'a pas réagi. La polymérisation du MMA est donc réalisée en présence de DDMAT et comparée à celles conduites avec CPAB, CTPPA. Malgré la faible constante de transfert du DDMAT (Ctr) vis-à-vis du MMA, un bon contrôle de la masse moléculaire du PMMA est obtenu. Une étude approfondie a révélé un mécanisme inattendu en « deux étapes » qui permet de rationaliser ce résultat. Enfin, une corrélation entre le contrôle de la polymérisation et le degré de solubilité dans le scCO2 des CTA a pu être établie, permettant de créer une ligne directrice pour sélectionner le meilleur CTA pour la polymérisation du MMA dans le scCO2. L’utilisation des PDMS-CPAB et PDMS-CTPPA, qui portent des groupes terminaux ayant des Ctr élevées vis-à-vis du MMA, montrent une amélioration globale de la polymérisation du MMA et du contrôle RAFT dans le scCO2 par rapport aux résultats utilisant le PDMS-DDMAT. La bonne solubilité des macro-CTA dans le scCO2 et le bon contrôle observé conduisent à la formation de copolymères à blocs PDMS-b-PMMA, et laissent entrevoir la mise en place d’un système d’auto-assemblage induit par la polymérisation.In this thesis, we focus on reversible addition-fragmentation chain transfer (RAFT) polymerisation in scCO2 with both molecular chain transfer agents (CTAs) (DDMAT, CPAB, CTPPA) and polydimethylsiloxane (PDMS)-based macromolecular CTAs (macro-CTAs) soluble in scCO2 (PDMS-DDMAT, PDMS-CPAB, PDMS-CTTPA), for the dispersion polymerisation of methyl methacrylate (MMA). Although the use of PDMS-DDMAT macro-CTAs led to stable PMMA particles, successful RAFT control was not attained, and part of the macro-CTA remained unreacted. Therefore, RAFT dispersion polymerisation of MMA in scCO2 was investigated using DDMAT and comparing to other molecular CTAs. Despite its low chain transfer constant (Ctr) towards MMA, DDMAT showed good control over PMMA molecular weight. A thorough investigation of the nucleation stage revealed an unexpected “in situ two-stage” mechanism that explains this result. Finally, a correlation between polymerisation control and the degree of solubility in scCO2 of the CTAs was stablished, giving rise to a guideline to select the best molecular CTA for MMA RAFT dispersion polymerisation in scCO2. The use of PDMS-CPAB and PDMS-CTPPA, which present chain-ends of high Ctr towards MMA, allowed an overall improvement of MMA polymerisation and RAFT control in scCO2 compared with PDMS-DDMAT. The good solubility of these macro-CTAs in scCO2 and the good control observed led to the formation of PDMS-b-PMMA block copolymers, suggesting the establishment of a polymerisation-induced self-assembly (PISA) process. This is a step forward towards PISA polymerisation via RAFT in scCO2 with fluorine-free macro-CTAs

Analyse du comportement de (macro)agents de transfert de chaîne lors de la polymérisation en dispersion de type RAFT dans le CO2 supercritique

In this thesis, we focus on reversible addition-fragmentation chain transfer (RAFT) polymerisation in scCO2 with both molecular chain transfer agents (CTAs) (DDMAT, CPAB, CTPPA) and polydimethylsiloxane (PDMS)-based macromolecular CTAs (macro-CTAs) soluble in scCO2 (PDMS-DDMAT, PDMS-CPAB, PDMS-CTTPA), for the dispersion polymerisation of methyl methacrylate (MMA). Although the use of PDMS-DDMAT macro-CTAs led to stable PMMA particles, successful RAFT control was not attained, and part of the macro-CTA remained unreacted. Therefore, RAFT dispersion polymerisation of MMA in scCO2 was investigated using DDMAT and comparing to other molecular CTAs. Despite its low chain transfer constant (Ctr) towards MMA, DDMAT showed good control over PMMA molecular weight. A thorough investigation of the nucleation stage revealed an unexpected “in situ two-stage” mechanism that explains this result. Finally, a correlation between polymerisation control and the degree of solubility in scCO2 of the CTAs was stablished, giving rise to a guideline to select the best molecular CTA for MMA RAFT dispersion polymerisation in scCO2. The use of PDMS-CPAB and PDMS-CTPPA, which present chain-ends of high Ctr towards MMA, allowed an overall improvement of MMA polymerisation and RAFT control in scCO2 compared with PDMS-DDMAT. The good solubility of these macro-CTAs in scCO2 and the good control observed led to the formation of PDMS-b-PMMA block copolymers, suggesting the establishment of a polymerisation-induced self-assembly (PISA) process. This is a step forward towards PISA polymerisation via RAFT in scCO2 with fluorine-free macro-CTAs.Cette thèse porte sur l’utilisation de la polymérisation radicalaire contrôlée par transfert réversible par addition-fragmentation (RAFT) conduite dans le dioxyde de carbone supercritique (scCO2) avec des agents de transfert de chaîne moléculaires (CTA) (DDMAT, CPAB, CTPPA) ou macromoléculaires (macro-CTA) à base de polydimétylsiloxane (PDMS) (PDMS-DDMAT, PDMS-CPAB, PDMS-CTTPA), pour la polymérisation en dispersion du méthacrylate de méthyle (MMA). Bien que le PDMS-DDMAT ait pu stabiliser les particules de PMMA produites dans le scCO2, le contrôle de la polymérisation n'a pas été atteint et une partie du macro-CTA n'a pas réagi. La polymérisation du MMA est donc réalisée en présence de DDMAT et comparée à celles conduites avec CPAB, CTPPA. Malgré la faible constante de transfert du DDMAT (Ctr) vis-à-vis du MMA, un bon contrôle de la masse moléculaire du PMMA est obtenu. Une étude approfondie a révélé un mécanisme inattendu en « deux étapes » qui permet de rationaliser ce résultat. Enfin, une corrélation entre le contrôle de la polymérisation et le degré de solubilité dans le scCO2 des CTA a pu être établie, permettant de créer une ligne directrice pour sélectionner le meilleur CTA pour la polymérisation du MMA dans le scCO2. L’utilisation des PDMS-CPAB et PDMS-CTPPA, qui portent des groupes terminaux ayant des Ctr élevées vis-à-vis du MMA, montrent une amélioration globale de la polymérisation du MMA et du contrôle RAFT dans le scCO2 par rapport aux résultats utilisant le PDMS-DDMAT. La bonne solubilité des macro-CTA dans le scCO2 et le bon contrôle observé conduisent à la formation de copolymères à blocs PDMS-b-PMMA, et laissent entrevoir la mise en place d’un système d’auto-assemblage induit par la polymérisation

Understanding the behaviour of (macro)chain transfer agents for RAFT controlled dispersion polymerisation in supercritical CO2

In this thesis, we focus on reversible addition- fragmentation chain transfer (RAFT) polymerisation in scCO2 with both molecular chain transfer agents (CTAs) (DDMAT, CPAB, CTPPA) and polydimethylsiloxane (PDMS)-based macromolecular CTAs (macro-CTAs) soluble in scCO2 (PDMS-DDMAT, PDMS-CPAB, PDMS-CTTPA), for the dispersion polymerisation of methyl methacrylate (MMA). Although the use of PDMS-DDMAT macro-CTAs led to stable PMMA particles, successful RAFT control was not attained, and part of the macro-CTA remained unreacted. Therefore, RAFT dispersion polymerisation of MMA in scCO2 was investigated using DDMAT and comparing to other molecular CTAs. Despite its low chain transfer constant (Ctr) towards MMA, DDMAT showed good control over PMMA molecular weight. A thorough investigation of the nucleation stage revealed an unexpected “in situ two-stage” mechanism that explains this result. Finally, a correlation between polymerisation control and the degree of solubility in scCO2 of the CTAs was stablished, giving rise to a guideline to select the best molecular CTA for MMA RAFT dispersion polymerisation in scCO2. The use of PDMS-CPAB and PDMS-CTPPA, which present chain-ends of high Ctr towards MMA, allowed an overall improvement of MMA polymerisation and RAFT control in scCO2 compared with PDMS-DDMAT. The good solubility of these macro-CTAs in scCO2 and the good control observed led to the formation of PDMS-b-PMMA block copolymers, suggesting the establishment of a polymerisation-induced self-assembly (PISA) process. This is a step forward towards PISA polymerisation via RAFT in scCO2 with fluorine-free macro-CTAs

NEOTROPICAL CARNIVORES: a data set on carnivore distribution in the Neotropics

Mammalian carnivores are considered a key group in maintaining ecological health and can indicate potential ecological integrity in landscapes where they occur. Carnivores also hold high conservation value and their habitat requirements can guide management and conservation plans. The order Carnivora has 84 species from 8 families in the Neotropical region: Canidae; Felidae; Mephitidae; Mustelidae; Otariidae; Phocidae; Procyonidae; and Ursidae. Herein, we include published and unpublished data on native terrestrial Neotropical carnivores (Canidae; Felidae; Mephitidae; Mustelidae; Procyonidae; and Ursidae). NEOTROPICAL CARNIVORES is a publicly available data set that includes 99,605 data entries from 35,511 unique georeferenced coordinates. Detection/non-detection and quantitative data were obtained from 1818 to 2018 by researchers, governmental agencies, non-governmental organizations, and private consultants. Data were collected using several methods including camera trapping, museum collections, roadkill, line transect, and opportunistic records. Literature (peer-reviewed and grey literature) from Portuguese, Spanish and English were incorporated in this compilation. Most of the data set consists of detection data entries (n = 79,343; 79.7%) but also includes non-detection data (n = 20,262; 20.3%). Of those, 43.3% also include count data (n = 43,151). The information available in NEOTROPICAL CARNIVORES will contribute to macroecological, ecological, and conservation questions in multiple spatio-temporal perspectives. As carnivores play key roles in trophic interactions, a better understanding of their distribution and habitat requirements are essential to establish conservation management plans and safeguard the future ecological health of Neotropical ecosystems. Our data paper, combined with other large-scale data sets, has great potential to clarify species distribution and related ecological processes within the Neotropics. There are no copyright restrictions and no restriction for using data from this data paper, as long as the data paper is cited as the source of the information used. We also request that users inform us of how they intend to use the data

NEOTROPICAL ALIEN MAMMALS: a data set of occurrence and abundance of alien mammals in the Neotropics

Biological invasion is one of the main threats to native biodiversity. For a species to become invasive, it must be voluntarily or involuntarily introduced by humans into a nonnative habitat. Mammals were among first taxa to be introduced worldwide for game, meat, and labor, yet the number of species introduced in the Neotropics remains unknown. In this data set, we make available occurrence and abundance data on mammal species that (1) transposed a geographical barrier and (2) were voluntarily or involuntarily introduced by humans into the Neotropics. Our data set is composed of 73,738 historical and current georeferenced records on alien mammal species of which around 96% correspond to occurrence data on 77 species belonging to eight orders and 26 families. Data cover 26 continental countries in the Neotropics, ranging from Mexico and its frontier regions (southern Florida and coastal-central Florida in the southeast United States) to Argentina, Paraguay, Chile, and Uruguay, and the 13 countries of Caribbean islands. Our data set also includes neotropical species (e.g., Callithrix sp., Myocastor coypus, Nasua nasua) considered alien in particular areas of Neotropics. The most numerous species in terms of records are from Bos sp. (n = 37,782), Sus scrofa (n = 6,730), and Canis familiaris (n = 10,084); 17 species were represented by only one record (e.g., Syncerus caffer, Cervus timorensis, Cervus unicolor, Canis latrans). Primates have the highest number of species in the data set (n = 20 species), partly because of uncertainties regarding taxonomic identification of the genera Callithrix, which includes the species Callithrix aurita, Callithrix flaviceps, Callithrix geoffroyi, Callithrix jacchus, Callithrix kuhlii, Callithrix penicillata, and their hybrids. This unique data set will be a valuable source of information on invasion risk assessments, biodiversity redistribution and conservation-related research. There are no copyright restrictions. Please cite this data paper when using the data in publications. We also request that researchers and teachers inform us on how they are using the data