A community in transition: Analysis of health and well‐being in people living during and following aridification

This paper considers skeletal and dental lesions to assess the effects of aridification on two skeletal samples from the Bronze Age in what is now the United Arab Emirates (UAE), located on the eastern end of the Arabian Peninsula. This paper hypothesized that the sample from Qarn al-Harf (QAH) Tomb 6 would show a greater prevalence of skeletal and dental lesions in comparison with that from QAH Tomb 5, because QAH Tomb 6 dates to a period of aridification when compared with the wetter Wadi Suq period (~2000 B.C.). The skeletal remains from two tombs from QAH cemetery are studied: one dated to the transition period from the Umm an-Nar to Wadi Suq period (~2000 B.C.) (Tomb 6, n = 141) and one Wadi Suq period tomb (Tomb 5, n = 44; 2000–1600 B.C.). Skeletal and dental lesions, including carious lesions, antemortem tooth loss, dental enamel hypoplasia, periosteal new bone formation, cribra orbitalia, and porotic hyperostosis, were recorded and used to assess differential lived experience. Findings from the two tombs are compared with five contemporary sites of the Umm an-Nar and Wadi Suq periods. Fisher's exact tests found more statistically significant differences in the prevalence of cribra orbitalia (p = 0.0050) and non-adult mortality (p = 0.0118) for the QAH Tomb 6 skeletal sample than that from QAH Tomb 5. No other skeletal or dental lesions were significantly different according to Fisher's exact tests. While not significant, periosteal new bone formation rates in QAH 6 in conjunction with cribra orbitalia rates suggest individuals were experiencing stressors that were not impacting QAH Tomb 5 individuals. Skeletal and dental lesion rates are not directly attributable to climate change; however, we argue that intense aridification around 2000 B.C. caused desiccated crops and an increased reliance on marine sources for QAH Tomb 6. This reliance likely promoted nutritionally deficient diets manifesting as observed higher rates of cribra orbitalia and periosteal new bone formation

Stepping Up or Falling Behind? Students’ Views on Universities and the Climate Crisis

This report presents the findings from a large-scale survey conducted among undergraduate students in twelve universities in Brazil, Fiji, Mozambique and Kenya. Carried out as part of the Transforming Universities for a Changing Climate (Climate-U) project, the survey centres on students’ attitudes and experiences in relation to climate change and perceptions of climate action in their universities. It responds to the overall aim of the project, which is to generate insights into how to maximise the contribution of universities to the mitigation and adaptation challenges of climate change, and to understand how universities might contribute to climate justice. The aim of this report is primarily descriptive; it serves to document the results of the survey comprehensively, providing basic analysis of the data including in comparative perspective across the four countries as well as serving as a reference for intended data users. To facilitate comparisons, a student home assets index is constructed using principal components analysis (PCA) and environmental attitudes are assessed using the Milfont and Duckitt (2010) reduced-form inventory and estimated using a latent-trait model based on Item Response Theory (IRT). Findings are reported mostly as descriptive statistics with a limited number of linear regression models being employed to estimate predictors of environmental attitudes. Findings focus on, inter alia, students’ backgrounds and areas of study, their experience, environmental attitudes, understandings and beliefs about climate change, feelings of personal responsibility and engagement with and willingness to participate in climate action as well as students’ assessments of what universities are doing and what they should be doing with regard to climate change. Overall, in all countries, students reported that they were most likely to learn about climate change from internet and social media sources. There is strong consensus that students should be learning more about climate change at their universities and that they are not satisfied with current learning. ‘Environmental concern’ was found to be higher among students studying science, agriculture, and health/ welfare related subjects, by women, by more economically advantaged students, and among students in Brazil. While students in Brazil were most likely to believe human actions are the major cause of climate change and provided the most pessimistic estimations of the impact of climate change, they were also the least likely to be confident that government action could make an impact. Conversely, students in Kenya had the greatest confidence in government action, were the most willing to participate in climate-change activities and were most optimistic about the impacts of climate change. The report provides indicative evidence for participating universities and others who may be intending to improve their engagement with students on issues relating to climate change and climate justice

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

BACKGROUND: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. METHODS: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). FINDINGS: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29-146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0- 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25-1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39-1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65-1·60]; p=0·92). INTERPRETATION: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. FUNDING: British Heart Foundation

Etude des interactions entre MEF2 et la voie de signalisation Notch au cours de la myogenèse adulte chez Drosophila melanogaster

La myogenèse des muscles indirects du vol (IFM) chez Drosophila melanogaster suit un schéma développemental précis. Au cours de l'embryogenèse, un groupe de cellules, les Précurseurs adultes Musculaires (AMP) se spécifient. Ces cellules deviennent des myoblastes qui prolifèrent au cours des stades larvaires et donneront par la suite les IFM adultes. Nos travaux se sont concentrés sur les interactions requises lors de la transition de myoblastes qui prolifèrent au statut de myoblaste différencié prêt à fusionner à la fibre musculaire. Il a été montré que les myoblastes qui prolifèrent ont une voie Notch active et que cette voie est inhibée dans les fibres en cours de différenciation. De plus, il a également été montré que les facteurs de transcription Myocyte Enhancer Factor 2 (MEF2), Vestigial (VG) et Scalloped (SD) sont nécessaires pour le développement des IFM et que VG est requis pour la répression de la voie Notch dans les fibres. Cette étude porte sur les interactions entre la voie Notch et MEF2 et les mécanismes mis en jeu pour réprimer la voie au cours de la différenciation. Nous avons montré que MEF2 peut réprimer la voie Notch dans des contexgtes non-musculaires. En utilisant un crible récent pour identifier des cibles potentielles de MEF2, nous avons cherché ceux qui sont également des cibles de SD. Parmi les résultats, deux cibles ont présenté un intérêt particulier, Delta et neuralized, deux composants de la voie de signalisation Notch. Nos résultats montrent dans un contexte ex vivo que les séquences enhancers de DI et neur sont régulées par MEF2/SD et MEF2/NOTCH respectivement. In vivo ces enhancers sont actifs dans les fibres des IFM en cours de différenciation pour DI et au cours de la différentiation tardive pour neur. Au cours de ma thèse, j'ai pu étudier l'effet de MEF2 sur la régulation de ces cibles pour comprendre leur rôle au cours de la différentiation des IFM.Myogenesis of indirect flight muscles (IFM) in Drosophila melanogaster follows a well defined cellular developmental scheme. During embryogenesis, a subset of cells, the Adult Muscle Precursors (AMPs), are specified. These cells will become proliferating myoblasts during the larval stages which will then give rise to the adult IFM. Our work focused on the interactions required during the transition between proliferating myoblasts to differentiated myoblasts ready to fuse to the muscle fiber. It has been previously shown that proliferating myoblasts express the Notch pathway, and that this pathway is inhibited in developing muscle fibers. On the other hand, it has also been shown that the Myocyte Enhancing Factor 2 (MEF2), Vestigial (VG) and Scalloped (SD) transcription factors are necessary for IFM development and that VG is required for Notch pathway repression in differentiating fibers. Our study focuses on the interactions between Notch and MEF2 and mechanisms by which the Notch pathway is inhibited during differentiation. Here we show that MEF2 is capable of inhibiting the Notch pathway in non myogenic cells. A previous screen for MEF2 potential targets identified Delta and Neuralized, two components of the Notch pathway. Both are expressed in developing fibers where MEF2, SD and VG are expressed. Our preliminary results show that MEF2 is required for Delta expression in developing IFMs and that this regulation is potentially dependent on an enhancer to which MEF2 and SD bind. We have identified a similar neuralized enhancer that seems to be potentially regulated by MEF2 and NICD. During my thesis I studied the effect of MEF2 on these targets in vivo and in vitro to understand the rote they play during IFM differentiation.PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Mef2 Interacts with the Notch Pathway during Adult Muscle Development in Drosophila melanogaster

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