Instrumental variable meta-analysis of randomised trials of epidural analgesia in labour to adjust for non-compliance

Objective: Intention-to-treat analysis of randomised controlled trials may cause bias towards the null where non-compliance with the allocated intervention occurs. Instrumental variable analysis allows estimation of the causal effect adjusted for non-compliance. The aim of this study is to compare intention-to-treat and instrumental variable meta-analysis of the association between epidural analgesia in labour and caesarean section. Study design and Setting: The study was restricted to 27 trials in a recent Cochrane Systematic Review. For trials with data on compliance, the association between epidural analgesia in labour and caesarean section was calculated using intention-to-treat analysis and instrumental variable analysis. Fixed-effects meta-analysis was used to calculate pooled risk ratios. Results: In 18 trials with data on compliance, 23% of women allocated to epidural analgesia did not comply and 27% of women allocated to the control received epidural analgesia. Data on outcomes in non-compliant groups were available for 10 trials. The pooled risk ratio for caesarean section following epidural analgesia in labour was 1.37 (95% CI 1.00-1.89, p=0.049) using instrumental variable analysis compared to 1.19 (95% CI 0.93-1.51, p=0.16) using intention-to-treat analysis. Conclusion: Intention-to-treat meta-analysis underestimates the effect of receiving epidural analgesia in labour on caesarean section compared to instrumental variable meta-analysis.NHMR

Intrahepatic cholestasis of pregnancy is not associated with stillbirth in an Australian maternity population

Dissertação de mestrado em Relações Internacionais (Estudos da Paz e da Segurança), apresentada à Faculdade de Economia da Universidade de CoimbraNo seguimento de experiências de violência extrema, no contexto de regimes políticos autoritários e violações sistemáticas de direitos humanos, algumas sociedades são confrontadas com questões relativas ao legado desse passado de violência, cujo impacto se faz sentir diretamente ao nível dos seus processos de (re)conciliação e reconstrução pós-conflito: o que será lembrado e esquecido, na construção da memória e verdade(s) sobre o conflito, e na transmissão do conhecimento às gerações futuras? O que deve acontecer aos indivíduos que planearam e aos que exerceram a violência? Que tipo de crimes serão julgados? Que tipo de processos judiciais e mecanismos de reparação serão estabelecidos e com que propósitos? Como é que uma sociedade pode (re)estabelecer os seus laços sociais intra-comunitários e até que ponto é que indivíduos que se percecionam mutuamente como inimigos alguma vez se poderão reconciliar? Estas são questões relacionadas com o fenómeno de justiça de transição, que se tem vindo a estabelecer enquanto norma global para as sociedades lidarem com o passado. A justiça de transição não só é uma área pouco teorizada como a sua teoria e prática dependem, em larga medida, de pressupostos adquiridos e partilhados com o modelo liberal internacional de construção da paz (peacebuilding). Esta dissertação procura problematizar mais especificamente um destes pressupostos, a dicotomia “vítimaperpetrador” e os processos de categorização inerentes ao modelo dominante de justiça de transição, em geral, tal como este é pensado e implementado ao nível internacional e nacional. Com base no estudo de caso do Ruanda, o nosso objetivo é demonstrar as insuficiências e limitações desta visão dicotómica para interpretar dinâmicas profundas de conflito considerando, ao invés, a diversidade de experiências de violência e vitimização que esta dicotomia exclui e refletindo sobre o seu impacto nas perspectivas de (re)conciliação pós-conflito, em particular da sociedade Ruandesa. De forma a atingir o objetivo a que nos propomos, a análise desta dissertação será orientada pela seguinte pergunta de partida: de que forma, no contexto de sociedades pós-conflito, como o Ruanda, pode uma narrativa de vitimização dominante ser desafiada por excluir uma diversidade de experiências de vitimização e violência, e que repercussões pode esta contestação originar para as perspectivas de (re)conciliação nesta sociedade? A nossa análise estará alicerçada em três hipóteses: (i) a dicotomia “vítima-perpetrator” é um elemento fundamental das iniciativas de transição pós-conflito apoiados pela ONU e implementados no contexto de intervenções internacionais; (ii) o Ruanda no pósgenocídio é caracterizado por uma narrativa nacional dominante de vitimização, baseada numa dicotomia “vítima-perpetrator” que é insuficiente para compreender a diversidade de experiências de violência e vitimização vivida por diferentes grupos sociais, excluindoas e deslegitimando-as; e (iii) os processos de justiça de transição orientados segundo esta dicotomia provocam novas formas de re-vitimização, por um lado, invisibilizando e deslegitimando certas experiências de violência e vitimização e, por outro lado, tomando estas categorias socio-políticas como absolutas, limitando assim a agência política dos indivíduos e a sua (re)integração social, colocando em causa o processo de (re)conciliação em sociedades divididas em geral, e na Ruandesa em particular. A validação destas hipóteses será baseada numa abordagem qualitativa à investigação, com base na interpretação qualitativa de informação textual recolhida através de fontes primárias e secundárias, e também na análise de discurso. O enquadramento teórico e conceptual com base no qual articularemos a nossa crítica combina contributos teóricos de duas disciplinas distintas mas complementares: a psicologia social, mais precisamente o trabalho de Carlos Beristain sobre a abordagem psicosocial, e a teoria das relações internacionais, especificamente a vertente mais crítica da abordagem construtivista. Da nossa análise decorreu a validação das nossas hipóteses iniciais, sendo que demonstrámos assim como a dicotomia “vítima-perpetrator” se tem tornado um elemento fundamental nas iniciativas de justiça de transição apoiadas pela ONU; discutimos e detalhámos as narrativas dominantes de justiça de transição e vitimização estabelecidas no Ruanda e as suas dinâmicas de exclusão e, por último, refletimos sobre como os processos de justiça de transição orientados por esta dicotomia promovem processos de revitimização e limitam as perspectivas de longo prazo de reconciliação em sociedades divididas, como exemplificado pelo Ruanda no pós-genocídio.Following experiences of extreme violence, in the context of authoritarian political regimes and systematic human rights violations, societies are faced with questions regarding the legacy of that past of violence, which directly impact on the processes of (re)conciliation and post-conflict rebuilding: what will be remembered and forgotten, in the construction of memory and truth(s) relating to the conflict, and in the transmission of knowledge to younger generations? What should happen to those individuals who planned and those who enacted the violence? What will be the range of crimes under investigation? What kind of judicial processes and mechanisms for reparations will be established and with what purposes? How can a community (re)establish its social intra-community ties and to what extent and in which way can individuals who perceive each other as enemies ever reconcile? These questions fall within the scope of the phenomenon of transitional justice, which has been establishing itself as a global norm on how societies should deal with the past. Not only is the field of transitional justice under theorized but its dominant discourse on theory and praxis relies heavily on core assumptions taken for granted, many of which borrowed from liberal peacebuilding. Our dissertation seeks to problematize one of these, in particular, the “victim-perpetrator” dichotomy and the categorizing inherent to the dominant transitional justice model thought of and implemented at both international and national levels. Drawing on Rwanda as a case study, this dissertation will aim at demonstrating the insufficiencies and limitations of this dichotomised view in understanding deeper conflict dynamics, by looking into the diversity of violence and victimhood experiences that this dichotomy excludes and by reflecting upon its impact on the prospects of post-conflict (re)conciliation, specifically with regards to contemporary Rwandan society. In order to achieve our proposed aim, the analysis in this dissertation will be guided by the following research question: In what way, in the context of a post-conflict society such as Rwanda, can an established dominant victimhood narrative be challenged for excluding the diversity of victimization and violence experiences, and what repercussions may that dispute have on the prospects of (re)conciliation in this society? Our analysis will be grounded on three working hypotheses: (i) the dichotomy “victim-perpetrator” is a fundamental element in UN-sanctioned post-conflict transition Initiatives implemented in the context of international interventions; (ii) post -genocide Rwanda is characterized by a national dominant victimhood narrative, based on a “victim-perpetrator” dichotomy which is insufficient to understand the full diversity of violence and victimhood experiences from different social groups, therefore excluding and delegitimizing them; and (iii) transitional justice processes framed by this dichotomy promote new forms of victimization, on the one hand, by making invisible (and, therefore, illegitimate) certain experiences of violence and victimhood and, on the other hand, by essentializing these sociopolitical categories, which ends up limiting individuals’ political agency and social reintegration, hindering the reconciliation process in divided societies and, particularly, in Rwanda. The validation of these hypotheses will be based on a qualitative research approach, in this way relying on the qualitative interpretation of textual (qualitative) data collected both from the literature and from primary evidence as well as discourse analysis. The theoretical and conceptual framework supporting our critique combines contributions from two distinct but, complementary fields of study: social psychology, in particular the work of Carlos Beristain on the psychosocial approach, and international relations theory, drawing on the more critical strand of constructivism. Our discussion successfully validated our three initial hypotheses, therefore asserting how the “victim-perpetrator” dichotomy has become a fundamental element in UN-sanctioned transit ional justice initiatives; discussing and detailing the dominant transitional justice and victimhood narratives in Rwanda and their dynamics of exclusion and, finally, reflecting on how transitional justice processes framed by this dichotomy promote re-victimization and hinder long-term reconciliation in divided societies such as post-genocide Rwanda

Variation in hospital caesarean section rates for preterm births

Background: Evidence about optimal mode of delivery for preterm birth is lacking and there is thought to be considerable variation in practice. Objective: To assess whether variation in hospital preterm caesarean section rates (Robson Classification Group 10) and outcomes are explained by casemix, labour or hospital characteristics. Materials and Methods: Population-based cohort study in NSW, 2007-2011. Births were categorised according to degree of prematurity and hospital service capability: 26-31 weeks, 32-33 weeks and 34-36 weeks. Hospital preterm caesarean rates were investigated using multilevel logistic regression models, progressively adjusting for casemix, labour and hospital factors. The association between hospital caesarean rates, and severe maternal and neonatal morbidity rates was assessed. Results: At 26-31 weeks the caesarean rate was 55.2% (7 hospitals, range 43.4-58.4%); 50.9% at 32-33 weeks (12 hospitals, 43.4- 58.1%); and 36.4% at 34-36 weeks (51 hospitals, 17.4-48.3%). At 26-31 weeks and 32-33 weeks, 81% and 59% of the variation between hospitals was explained with no hospital significantly different from the state average after adjustment. At 34-36 weeks, although 59% of the variation was explained, substantial unexplained variation persisted. Hospital caesarean rates were not associated with severe maternal morbidity rates at any gestational age. At 26-31 weeks medium and high caesarean rates were associated with higher severe neonatal morbidity rates, but there was no evidence of this association ≥32 weeks. 3 Conclusion: Both casemix and practice differences contributed to the variation in hospital caesarean rates. Low preterm caesarean rates were not associated with worse outcomes.Australian National Health and Medical Research Council; Australian Research Counci

Пойменные ценокомплексы Красноярского водохранилища в районе залива реки Убей

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Forest Goers and Multidrug-Resistant Malaria in Cambodia: An Ethnographic Study.

Multidrug-resistant Plasmodium falciparum malaria on the Cambodia-Thailand border is associated with working in forested areas. Beyond broad recognition of "forest-going" as a risk factor for malaria, little is known about different forest-going populations in this region. In Oddar Meanchey Province in northwestern Cambodia, qualitative ethnographic research was conducted to gain an in-depth understanding of how different populations, mobility and livelihood patterns, and activities within the forest intersect with potentiate malaria risk and impact on the effectiveness of malaria control and elimination strategies. We found that most forest-going in this area is associated with obtaining precious woods, particularly Siamese rosewood. In the past, at-risk populations included large groups of temporary migrants. As timber supplies have declined, so have these large migrant groups. However, groups of local residents continue to go to the forest and are staying for longer. Most forest-goers had experienced multiple episodes of malaria and were well informed about malaria risk. However, economic realities mean that local residents continue to pursue forest-based livelihoods. Severe constraints of available vector control methods mean that forest-goers have limited capacity to prevent vector exposure. As forest-goers access the forest using many different entry and exit points, border screening and treatment interventions will not be feasible. Once in the forest, groups often converge in the same areas; therefore, interventions targeting the mosquito population may have a potential role. Ultimately, a multisectoral approach as well as innovative and flexible malaria control strategies will be required if malaria elimination efforts are to be successful

Households or hotspots? Defining intervention targets for malaria elimination in Ratanakiri Province, eastern Cambodia

Background. Malaria “hotspots” have been proposed as potential intervention units for targeted malaria elimination. Little is known about hotspot formation and stability in settings outside sub-Saharan Africa. Methods. Clustering of Plasmodium infections at the household and hotspot level was assessed over 2 years in 3 villages in eastern Cambodia. Social and spatial autocorrelation statistics were calculated to assess clustering of malaria risk, and logistic regression was used to assess the effect of living in a malaria hotspot compared to living in a malaria-positive household in the first year of the study on risk of malaria infection in the second year. Results. The crude prevalence of Plasmodium infection was 8.4% in 2016 and 3.6% in 2017. Living in a hotspot in 2016 did not predict Plasmodium risk at the individual or household level in 2017 overall, but living in a Plasmodium-positive household in 2016 strongly predicted living in a Plasmodium-positive household in 2017 (Risk Ratio, 5.00 [95% confidence interval, 2.09–11.96], P < .0001). There was no consistent evidence that malaria risk clustered in groups of socially connected individuals from different households. Conclusions. Malaria risk clustered more clearly in households than in hotspots over 2 years. Household-based strategies should be prioritized in malaria elimination programs in this region

The discovery of I-BRD9, a selective cell active chemical probe for bromodomain containing protein 9 inhibition

Acetylation of histone lysine residues is one of the most well-studied post-translational modifications of chromatin, selectively recognized by bromodomain “reader” modules. Inhibitors of the bromodomain and extra terminal domain (BET) family of bromodomains have shown profound anticancer and anti-inflammatory properties, generating much interest in targeting other bromodomain-containing proteins for disease treatment. Herein, we report the discovery of I-BRD9, the first selective cellular chemical probe for bromodomain-containing protein 9 (BRD9). I-BRD9 was identified through structure-based design, leading to greater than 700-fold selectivity over the BET family and 200-fold over the highly homologous bromodomain-containing protein 7 (BRD7). I-BRD9 was used to identify genes regulated by BRD9 in Kasumi-1 cells involved in oncology and immune response pathways and to the best of our knowledge, represents the first selective tool compound available to elucidate the cellular phenotype of BRD9 bromodomain inhibition

High Mobility and Low Use of Malaria Preventive Measures Among the Jarai Male Youth Along the Cambodia?Vietnam Border

Malaria control along the Vietnam?Cambodia border presents a challenge for both countries\u27 malaria elimination targets as the region is forested, inhabited by ethnic minority populations, and potentially characterized by early and outdoor malaria transmission. A mixed methods study assessed the vulnerability to malaria among the Jarai population living on both sides of the border in the provinces of Ratanakiri (Cambodia) and Gia Lai (Vietnam). A qualitative study generated preliminary hypotheses that were quantified in two surveys, one targeting youth (N = 498) and the other household leaders (N = 449). Jarai male youth, especially in Cambodia, had lower uptake of preventive measures (57.4%) and more often stayed overnight in the deep forest (35.8%) compared with the female youth and the adult population. Among male youth, a high-risk subgroup was identified that regularly slept at friends\u27 homes or outdoors, who had fewer bed nets (32.5%) that were torn more often (77.8%). The vulnerability of Jarai youth to malaria could be attributed to the transitional character of youth itself, implying less fixed sleeping arrangements in nonpermanent spaces or non-bed sites. Additional tools such as long-lasting hammock nets could be suitable as they are in line with current practices