37 research outputs found
Les effets de la vente en ligne sur les inégalités territoriales d'accÚs au commerce. Vers un nivellement des disparités urbain-périurbain ?
LâaccessibilitĂ© gĂ©ographique des populations aux biens est diffĂ©renciĂ©e selon les espaces. Les populations des centres-villes peuvent accĂ©der Ă pieds, Ă proximitĂ© de leur domicile Ă des magasins offrant un large choix de biens, alors que les populations pĂ©riurbaines doivent parcourir plusieurs kilomĂštres en voiture pour accĂ©der au premier magasin de proximitĂ©. Depuis les annĂ©es 1990, le commerce Ă destination des particuliers (business-to-consumer) connaĂźt de fortes Ă©volutions, avec le dĂ©veloppement dâInternet et de la vente en ligne. Cette « Ă©lectronisation » offre la possibilitĂ© dâune sĂ©paration croissante des fonctions du commerce, notamment la vente en elle-mĂȘme et la logistique de distribution . Ainsi, la livraison Ă domicile et celle dans des relais-livraison se sont affirmĂ©es comme des modes de distribution alternatifs aux magasins, bouleversant les cadres de lâanalyse de lâaccessibilitĂ© des populations aux commerces, notamment dans les espaces pĂ©riurbains. LâaccessibilitĂ© est entendue ici comme lâensemble des contraintes spatiales, temporelles et modales pesant sur les dĂ©placements nĂ©cessaires pour accĂ©der Ă un bien.Les principales formes de distribution de la vente en ligne, les livraisons Ă domicile et en relais-livraison, proposent une redĂ©finition de lâaccessibilitĂ© Ă un large Ă©ventail de biens matĂ©riels, en offrant ces biens Ă domicile et/ou dans des commerces de proximitĂ© plutĂŽt que, pour certains biens, dans un magasin du centre-ville. Les disparitĂ©s dâaccessibilitĂ©s aux commerces, parfois fortes selon le type de bien recherchĂ©, marquĂ©es par un gradient urbain-pĂ©riurbain et par une hĂ©tĂ©rogĂ©nĂ©itĂ© des territoires pĂ©riurbains, devraient sâen trouver significativement nivelĂ©es par une multiplication attendue des points de distribution, notamment dans des territoires qui nâen disposaient pas. Cependant cela nĂ©cessite, dâune part, que les habitants des territoires concernĂ©s adoptent largement le commerce Ă©lectronique et tirent parti des options de livraison. Dâautre part, le dĂ©veloppement de la vente en ligne entraĂźne une transformation de lâoffre commerciale existante par la concurrence quâelle opĂšre. Certaines localisations commerciales existantes sâen trouvent fragilisĂ©es ou remises en cause, tout autant que lâaccessibilitĂ© et les pratiques dâachat des populations rĂ©sidant dans ces territoires.Les trois parties du rapport fournissent des rĂ©ponses et des Ă©clairages diffĂ©renciĂ©s sur ces interrogations, plus prĂ©cisĂ©ment sur celle formulĂ©e en titre. La premiĂšre partie sera focalisĂ©e sur l'accĂšs aux produits alimentaires et de consommation courante via l'analyse des zones de dessertes des cybermarchĂ©s. La seconde partie s'intĂ©ressera Ă un acteur Ă©mergent du e-commerce: les points relais. Enfin la derniĂšre partie essaiera de saisir plus finement les usages et pratiques des mĂ©nages en termes de ventes en ligne
Lack of MEF2A Î7aa mutation in Irish families with early onset ischaemic heart disease, a family based study
BACKGROUND: Ischaemic heart disease (IHD) is a complex disease due to the combination of environmental and genetic factors. Mutations in the MEF2A gene have recently been reported in patients with IHD. In particular, a 21 base pair deletion (Î7aa) in the MEF2A gene was identified in a family with an autosomal dominant pattern of inheritance of IHD. We investigated this region of the MEF2A gene using an Irish family-based study, where affected individuals had early-onset IHD. METHODS: A total of 1494 individuals from 580 families were included (800 discordant sib-pairs and 64 parent-child trios). The Î7aa region of the MEF2A gene was investigated based on amplicon size. RESULTS: The Î7aa mutation was not detected in any individual. Variation in the number of CAG (glutamate) and CCG (proline) residues was detected in a nearby region. However, this was not found to be associated with IHD. CONCLUSION: The Î7aa mutation was not detected in any individual within the study population and is unlikely to play a significant role in the development of IHD in Ireland. Using family-based tests of association the number of tri-nucleotide repeats in a nearby region of the MEF2A gene was not associated with IHD in our study group
HMGA1 Induces Intestinal Polyposis in Transgenic Mice and Drives Tumor Progression and Stem Cell Properties in Colon Cancer Cells
Although metastatic colon cancer is a leading cause of cancer death worldwide, the molecular mechanisms that enable colon cancer cells to metastasize remain unclear. Emerging evidence suggests that metastatic cells develop by usurping transcriptional networks from embryonic stem (ES) cells to facilitate an epithelial-mesenchymal transition (EMT), invasion, and metastatic progression. Previous studies identified HMGA1 as a key transcription factor enriched in ES cells, colon cancer, and other aggressive tumors, although its role in these settings is poorly understood.To determine how HMGA1 functions in metastatic colon cancer, we manipulated HMGA1 expression in transgenic mice and colon cancer cells. We discovered that HMGA1 drives proliferative changes, aberrant crypt formation, and intestinal polyposis in transgenic mice. In colon cancer cell lines from poorly differentiated, metastatic tumors, knock-down of HMGA1 blocks anchorage-independent cell growth, migration, invasion, xenograft tumorigenesis and three-dimensional colonosphere formation. Inhibiting HMGA1 expression blocks tumorigenesis at limiting dilutions, consistent with depletion of tumor-initiator cells in the knock-down cells. Knock-down of HMGA1 also inhibits metastatic progression to the liver in vivo. In metastatic colon cancer cells, HMGA1 induces expression of Twist1, a gene involved in embryogenesis, EMT, and tumor progression, while HMGA1 represses E-cadherin, a gene that is down-regulated during EMT and metastatic progression. In addition, HMGA1 is among the most enriched genes in colon cancer compared to normal mucosa.Our findings demonstrate for the first time that HMGA1 drives proliferative changes and polyp formation in the intestines of transgenic mice and induces metastatic progression and stem-like properties in colon cancer cells. These findings indicate that HMGA1 is a key regulator, both in metastatic progression and in the maintenance of a stem-like state. Our results also suggest that HMGA1 or downstream pathways could be rational therapeutic targets in metastatic, poorly differentiated colon cancer
A pilot study to evaluate a community pharmacyâbased monitoring system to identify adverse drug reactions associated with paediatric medicines use
Economic Analysis of Labor Markets and Labor Law: An Institutional/Industrial Relations Perspective
The Effectiveness of Transnational Non-State Governance: The Role of Domestic Regulations and Compliance Assessment in Practice
Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.
BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5âĂâ1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1â-ârelative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23â848 participants were enrolled and 11â636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74â341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca
Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK
Background
A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials.
Methods
This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5âĂâ1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1â-ârelative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674.
Findings
Between April 23 and Nov 4, 2020, 23â848 participants were enrolled and 11â636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0â75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4â97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8â80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74â341 person-months of safety follow-up (median 3·4 months, IQR 1·3â4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation.
Interpretation
ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials