Moving from medical to health systems classifications of deaths : extending verbal autopsy to collect information on the circumstances of mortality

Acknowledgements The authors would also like to acknowledge the field staff at the MRC, SA/Wits Agincourt Unit, particularly Sizzy Ngobeni. The authors also acknowledge Drs Malin Eriksson and Edward Fottrell at Umeå Centre for Global Health Research *UCGHR) who contributed to the development of the SF-VA indicators, Dr Nawi Ng at UCGHR who advised on the cause of death categories, and Dr Kerstin Edin at UCGHR who provided comments on the manuscript categories, and Dr Kerstin Edin who provided comments on the manuscript. Funding A Health Systems Research Initiative Development Grant from the UK Department for International Development (DFID), Economic and Social Research Council (ESRC), Medical Research Council (MRC (and the Wellcome Trust (MR/N005597/1) funds the research presented in this paper. Support for the Agincourt HDSS including verbal autopsies was provided by The Wellcome Trust, UK (grants 058893/Z/99/A; 069683/Z/02/Z; 085477/Z/08/Z; 085477/B/08/Z), and the University of the Witwatersrand and Medical Research Council, South Africa.Peer reviewedPublisher PD

Initiating a participatory action research process in the Agincourt health and socio–demographic surveillance site

Financial disclosure Funding: The research presented in this paper is funded by a Development Grant as part of the Health Systems Research Initiative from Department for International Development (DFID)/Medical Research Council (MRC)/Wellcome Trust/Economic and Social Research Council (ESRC) (MR/N005597/1). The fieldwork was completed with the Umeå Centre for Global Health Research, with support from FORTE: Swedish Council for Health, Working Life and Welfare (grant No. 2006–1512). The School of Public Health at the University of the Witwatersrand, the South African Medical Research Council, and the Wellcome Trust, UK support the MRC/Wits Rural Public Health and Health Transitions Research Unit and Agincourt HDSS (Grants 058893/Z/99/A; 069683/Z/02/Z; 085477/Z/08/Z; 085477/B/08/Z). OW is a recipient of an MSc Chevening Scholarship, the UK government's global scholarship programme, funded by the Foreign and Commonwealth Office (FCO) and partner organizations (Chevening Ref.: NGCV–2015–1194).Peer reviewedPublisher PD

Synthesis and characterization of metal (M=Al or Ga) 2-phosphino (phenolate/benzenethiolate) complexes and their electrochemical behavior in the presence of CO2

A series of Group 13 complexes MLX2 (M = Al or Ga, L = SC6H4-2-PtBu2 or OC6H4-2-PtBu2, X = Me or C6F5) have been synthesized and characterized by multinuclear NMR spectroscopy and single crystal X-ray diffraction. Reactions of Me3Al or Me3Ga with an equivalent of either 2-tBu2P(C6H4)OH (1) or 2-tBu2P(C6H4)SH (5) resulted in the formation of four new (2,3,6, and 7), 4-coordinate dimethyl chelate (S,P or O,P) complexes via methane elimination. The dimethyl gallium complexes (3 and 7) underwent a further reaction with excess B(C6F5)3, and through ligand exchange (methyl/pentafluorophenyl), resulted in the disubstituted bis(pentafluorophenyl) analogs (4 and 8). Cyclic voltammetry (CV) experiments for all compounds in the presence of and the absence of (1–8) CO2 were performed. For compounds showing cathodic reduction waves under CO2 (2,3,4, and 6), bulk electrolysis experiments were performed. Electrochemical studies indicate that, for several compounds, a transient CO2 adduct is formed which undergoes a one-electron, irreversible (or partially irreversible) reduction to form an unstable radical anion

Rethinking collaboration: developing a learning platform to address under-five mortality in Mpumalanga province, South Africa

Sophie Witter - orcid: 0000-0002-7656-6188 https://orcid.org/0000-0002-7656-6188Following 50 years of apartheid, South Africa introduced visionary health policy committing to the right to health as part of a primary health care (PHC) approach. Implementation is seriously challenged, however, in an often-dysfunctional health system with scarce resources and a complex burden of avoidable mortality persists. Our aim was to develop a process generating evidence of practical relevance on implementation processes among people excluded from access to health systems. Informed by health policy and systems research, we developed a collaborative learning platform in which we worked as co-researchers with health authorities in a rural province. This article reports on the process and insights brought by health systems stakeholders. Evidence gaps on under-five mortality were identified with a provincial Directorate after which we collected quantitative and qualitative data. We applied verbal autopsy to quantify levels, causes and circumstances of deaths and participatory action research to gain community perspectives on the problem and priorities for action. We then re-convened health systems stakeholders to analyse and interpret these data through which several systems issues were identified as contributory to under-five deaths: staff availability and performance; service organization and infrastructure; multiple parallel initiatives; and capacity to address social determinants. Recommendations were developed ranging from immediate low- and no-cost re-organization of services to those where responses from higher levels of the system or outside were required. The process was viewed as acceptable and relevant for an overburdened system operating ‘in the dark’ in the absence of local data. Institutional infrastructure for evidence-based decision-making does not exist in many health systems. We developed a process connecting research evidence on rural health priorities with the means for action and enabled new partnerships between communities, authorities and researchers. Further development is planned to understand potential in deliberative processes for rural PHC.The research presented in this article was funded by the Health Systems Research Initiative from Department for International Development (DFID)/Medical Research Council (MRC)/Wellcome Trust/Economic and Social Research Council (ESRC) (MR/N005597/1 and MR/P014844/1). The fieldwork was completed with the Umea° Centre for Global Health Research, with support from FORTE: Swedish Council for Health, Working Life and Welfare (grant no. 2006–1512). The School of Public Health at the University of the Witwatersrand, the South African Medical Research Council, and the Wellcome Trust, UK support the MRC/Wits Rural Public Health and Health Transitions Research Unit and Agincourt HDSS (grants nos. 058893/Z/99/A; 069683/Z/02/Z; 085477/Z/08/Z; 085477/B/08/Z). OW is a recipient of an MSc Chevening Scholarship, the UK government’s global scholarship programme, funded by the Foreign and Commonwealth Office (FCO) and partner organizations (Chevening Ref.: NGCV-2015-1194).http://dx.doi.org/10.1093/heapol/czz04734pubpub

Rethinking collaboration : developing a learning platform to address under-five mortality in Mpumalanga province, South Africa

The authors would also like to acknowledge colleagues at the MRC/Wits Agincourt unit, who made important contributions to the work. The research presented in this article was funded by the Health Systems Research Initiative from Department for International Development (DFID)/Medical Research Council (MRC)/Wellcome Trust/Economic and Social Research Council (ESRC) (MR/N005597/1 and MR/P014844/1). The fieldwork was completed with the Umeå Centre for Global Health Research, with support from FORTE: Swedish Council for Health, Working Life and Welfare (grant no. 2006–1512). The School of Public Health at the University of the Witwatersrand, the South African Medical Research Council, and the Wellcome Trust, UK support the MRC/Wits Rural Public Health and Health Transitions Research Unit and Agincourt HDSS (grants nos. 058893/Z/99/A; 069683/Z/02/Z; 085477/Z/08/Z; 085477/B/08/Z). OW is a recipient of an MSc Chevening Scholarship, the UK government’s global scholarship programme, funded by the Foreign and Commonwealth Office (FCO) and partner organizations (Chevening Ref.: NGCV-2015-1194).Peer reviewedPublisher PD

Temporal changes in the epidemiology, management, and outcome from acute respiratory distress syndrome in European intensive care units: a comparison of two large cohorts

Background: Mortality rates for patients with ARDS remain high. We assessed temporal changes in the epidemiology and management of ARDS patients requiring invasive mechanical ventilation in European ICUs. We also investigated the association between ventilatory settings and outcome in these patients. Methods: This was a post hoc analysis of two cohorts of adult ICU patients admitted between May 1–15, 2002 (SOAP study, n = 3147), and May 8–18, 2012 (ICON audit, n = 4601 admitted to ICUs in the same 24 countries as the SOAP study). ARDS was defined retrospectively using the Berlin definitions. Values of tidal volume, PEEP, plateau pressure, and FiO2 corresponding to the most abnormal value of arterial PO2 were recorded prospectively every 24 h. In both studies, patients were followed for outcome until death, hospital discharge or for 60 days. Results: The frequency of ARDS requiring mechanical ventilation during the ICU stay was similar in SOAP and ICON (327[10.4%] vs. 494[10.7%], p = 0.793). The diagnosis of ARDS was established at a median of 3 (IQ: 1–7) days after admission in SOAP and 2 (1–6) days in ICON. Within 24 h of diagnosis, ARDS was mild in 244 (29.7%), moderate in 388 (47.3%), and severe in 189 (23.0%) patients. In patients with ARDS, tidal volumes were lower in the later (ICON) than in the earlier (SOAP) cohort. Plateau and driving pressures were also lower in ICON than in SOAP. ICU (134[41.1%] vs 179[36.9%]) and hospital (151[46.2%] vs 212[44.4%]) mortality rates in patients with ARDS were similar in SOAP and ICON. High plateau pressure (> 29 cmH2O) and driving pressure (> 14 cmH2O) on the first day of mechanical ventilation but not tidal volume (> 8 ml/kg predicted body weight [PBW]) were independently associated with a higher risk of in-hospital death. Conclusion: The frequency of and outcome from ARDS remained relatively stable between 2002 and 2012. Plateau pressure > 29 cmH2O and driving pressure > 14 cmH2O on the first day of mechanical ventilation but not tidal volume > 8 ml/kg PBW were independently associated with a higher risk of death. These data highlight the continued burden of ARDS and provide hypothesis-generating data for the design of future studies

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field