Planning Framework for Human Resources for Health for Maternal and Newborn Care

With approximately 1.3 billion births estimated to be taking place globally over a decade up to 2020, the demand for maternal and newborn health (MNH) workforce continues to be a key aspect of public health service delivery. Human resources for health (HRH) projection models can contribute the quantitative evidence required for policy design for education commissioning and distribution of skilled personnel. To date, HRH supply and requirement projection models have not been developed specifically for system-based subnational planning within maternal and newborn care. In addition, current methodologies are often limited to national level and have a professional silo approach to considering the workforce, with informing policy and planning as a secondary consideration. The aim of this thesis was to fill the gap through improved understanding of the role of HRH projections for policy and development of a new model for projecting the future MNH clinical teams with spatial equity and system perspective at the centre of the planning framework. The specific objectives were to • review the literature for strengths and limitations for current HRH planning and outline the main components of an evidence-informed MNH-HRH planning framework with relevance to subnational contexts and MNH systems • translate the main components into a working prototype as a spreadsheet-based model to estimate and MNH-HRH requirements and supply for each occupation • apply the MNH-HRH planning model in three countries from low to high income contexts and critique the implications for future research and development in this field. Following the construction of a new planning framework, a working prototype called the ‘MNH.HRH Planning App’ was developed. The spreadsheet-based model was applied using secondary data sources to England, Bangladesh, and Ethiopia which have varied health systems, levels of spatial disaggregation and HRH structures for MNH care. The thesis concludes by highlighting the implications of the new planning framework for the future development of a web-based MNH.HRH Planning App, potential for engaging policy-makers for evidence-informed planning and contributes to the wider discourse on the use of quantitative projection models for planning the future human resources for healthcare

Participation in Transition(s):Reconceiving Public Engagements in Energy Transitions as Co-Produced, Emergent and Diverse

This paper brings the transitions literature into conversation with constructivist Science and Technology Studies (STS) perspectives on participation for the first time. In doing so we put forward a conception of public and civil society engagement in sustainability transitions as co-produced, relational, and emergent. Through paying close attention to the ways in which the subjects, objects, and procedural formats of public engagement are constructed through the performance of participatory collectives, our approach offers a framework to open up to and symmetrically compare diverse and interconnected forms of participation that make up wider socio-technical systems. We apply this framework in a comparative analysis of four diverse cases of civil society involvement in UK low carbon energy transitions. This highlights similarities and differences in how these distinct participatory collectives are orchestrated, mediated, and subject to exclusions, as well as their effects in producing particular visions of the issue at stake and implicit models of participation and ‘the public’. In conclusion we reflect on the value of this approach for opening up the politics of societal engagement in transitions, building systemic perspectives of interconnected ‘ecologies of participation’, and better accounting for the emergence, inherent uncertainties, and indeterminacies of all forms of participation in transitions

Mathematical modeling supports the presence of neutrophil depriming in vivo.

Abstract Following migration into the intestinal mucosa in inflammatory bowel disease (IBD), neutrophils enter the intestinal lumen and are excreted. This provides a basis for quantification of disease activity by measuring excreted label following injection of In-111-labeled neutrophils. In severe pan-colitis, 50% of the injected In-111 is typically recovered in the feces, indicating that 50% of neutrophil turnover is via fecal excretion. Neutrophils have an intravascular lifespan of ~10 h and a distribution volume of ~10 L, so total body neutrophil turnover is 10.N/10 cells/h, where N is the peripheral blood neutrophil count (cells/L). Neutrophil loss via the colon in a patient with 50% fecal In-111 loss is therefore N/120 cells/min. Pan-colonic mucosal-blood flow in pan-colitis is 200 mL/min, which would deliver N/5 neutrophils to the colon per min. Therefore, 5/120, or 4%, of incoming neutrophils undergo migration into inflamed bowel. If the 96% of nonmigrating cells exit in a primed state, then at steady state >90% of circulating neutrophils would be primed if no depriming took place. As the highest level of priming seen in IBD is ~40%, this indicates that depriming within the circulation must take place. Using the above values in the steady state equation relating priming rate to depriming rate plus primed-cell destruction rate gives a mean depriming time of 35 min. We conclude that a very small proportion of neutrophils entering a site of inflammation migrate and that in vivo depriming must take place to limit the numbers of primed neutrophils in the circulation.This study was supported by the Wellcome Trust and the UK‐US Fulbright Commission; CS holds a Wellcome Trust Postdoctoral Clinical Research Fellowship and a Fulbright Scholar award. The work in the Chilvers lab is funded by the Wellcome Trust, MRC, Asthma‐UK, BBSRC, Gates Foundation and NIHR Cambridge BRC.This is the final published version, also available from http://physreports.physiology.org/content/2/3/e00241.long

The contribution of social work field education to work-integrated learning.

The International Journal of Work-Integrated Learning is an Open Access journal which means that all content is freely available without charge to the user or his/her institution. Users are allowed to read, download, copy, distribute, print, search, or link to the full texts of the articles, or use them for any other lawful purpose, without asking prior permission from the publisher or the author.fals

Alveolar Macrophages Isolated Directly From Human Cytomegalovirus (HCMV)-Seropositive Individuals Are Sites of HCMV Reactivation In Vivo.

Human cytomegalovirus (HCMV) causes significant morbidity in the immunocompromised host. Following primary infection, the virus establishes latent infection in progenitor cells of the myeloid lineage. These cells exhibit limited viral gene transcription and no evidence of de novo virion production. It is well recognized that differentiation of latently infected myeloid progenitor cells to dendritic or macrophage-like cells permits viral reactivation in vitro. This has been used to support the concept that viral reactivation in HCMV carriers routinely occurs from such terminally differentiated myeloid cells in vivo. However, to date this has not been shown for in vivo-differentiated macrophages. This study is the first to demonstrate that alveolar macrophages from HCMV carriers express immediate early lytic genes and produce infectious virus. This supports the view, until now based on in vitro data, that terminally differentiated myeloid cells in vivo are sites of HCMV reactivation and potential centers of viral dissemination in latently infected individuals with no evidence of virus disease or dissemination.This work was supported by the UK Medical Research Council (grant 0701279 to J. S.) and the National Institute for Health Research UK Biomedical Research Centre (to J. S. and E. R. C.).This is the final published version. It first appeared at http://jid.oxfordjournals.org/content/211/12/1936

Phenotypically distinct neutrophils patrol uninfected human and mouse lymph nodes.

Neutrophils play a key role in innate immunity. As the dominant circulating phagocyte, they are rapidly recruited from the bloodstream to sites of infection or injury to internalize and destroy microbes. More recently, neutrophils have been identified in uninfected organs, challenging the classical view of their function. Here we show that neutrophils were present in lymph nodes (LNs) in homeostasis. Using flow cytometry and confocal imaging, we identified neutrophils within LNs in naive, unchallenged mice, including LNs draining the skin, lungs, and gastrointestinal tract. Neutrophils were enriched within specific anatomical regions, in the interfollicular zone, a site of T cell activation. Intravital two-photon microscopy demonstrated that LN neutrophils were motile, trafficked into LNs from both blood and tissues via high endothelial venules and afferent lymphatics, respectively, and formed interactions with dendritic cells in LNs. Murine and human LN neutrophils had a distinct phenotype compared with circulating neutrophils, with higher major histocompatibility complex II (MHCII) expression, suggesting a potential role in CD4 T cell activation. Upon ex vivo stimulation with IgG immune complex (IC), neutrophils up-regulated expression of MHCII and costimulatory molecules and increased T cell activation. In vivo, neutrophils were capable of delivering circulating IC to LNs, suggesting a broader functional remit. Overall, our data challenge the perception that neutrophil patrol is limited to the circulation in homeostasis, adding LNs to their routine surveillance territory.L.S.C.L. was funded by Wellcome Trust (104384/Z/14/Z). M.R.C. is supported by National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre, Chan-Zuckerburg Initiative Human Cell Atlas Technology Development Grant, Medical Research Council New Investigator Research Grant (MR/N024907/1), Arthritis Research UK Cure Challenge Research Grant (21777), and NIHR Research Professorship (RP-2017-08- ST2-002)

Kinship in Aegean Prehistory? Ancient DNA in Human Bones from Mainland Greece and Crete

Attempts were made to detect ancient DNA (aDNA) in samples of 89 human skeletons from Neolithic and Bronze Age sites in Greece and Crete. Ancient DNA was absent in specimens from Nea Nicomedia, Lerna, Kato Zakro: Karaviádena, and Mycenae Grave Circle A. For each of three skeletons sampled from Antron Grave Circle B, polymerase chain reactions (PCRs) gave products for nuclear but not mitochondrial DNA, but the yield of DNA was low and inconsistent, with replicate PCRs failing to give reproducible results. At Kouphovouno evidence for mitochondrial and/or nuclear aDNA was obtained from eight of the 20 skeletons that were examined, while at Mycenae Grave Circle B evidence for mitochondrial aDNA was obtained for four of the 22 skeletons that were studied, and in two cases confirmed the evidence of close kinship that had already been suggested by facial reconstruction: this in turn raises interesting questions of social relationships and the role of high-status women in MBA/LBA society. We conclude that, although aDNA might be present in some Eastern Mediterranean skeletons from later centuries of the Bronze Age, it is not commonly found in material from this period and is likely to be absent from older material.Στη μελέτη αυτή έγιναν προσπάθειες να αναγνωριστεί αρχαίο DNA (aDNA) σε δείγματα ογδόντα εννέα ανθρώπινων σκελετών προερχομένων από θέσεις της Νεολιθικής περιόδου και της Εποχής του Χαλκού στην Ελλάδα και την Κρήτη. Αρχαίο DNA δεν εντοπίστηκε σε δείγματα από τη Νέα Νικομήδεια, τη Λέρνα, την Κάτω Ζάκρο (Καραβιάδενα) και τον Ταφικό Κύκλο Α των Μυκηνών. Για κάθε έναν από τους τρεις σκελετούς, οι οποίοι εξετάστηκαν από τον Ταφικό Κύκλο Β της Αντρώνας, οι αλυσιδωτές αντιδράσεις πολυμεράσης (PCRs) απέφεραν αποτελέσματα για πυρηνικό αλλά όχι μιτοχονδριακό DNA. Η παραγωγή DNA ήταν χαμηλή και αντιφατική, με τα αντίγραφα πολυμεράσης να αποτυγχάνουν να αποφέρουν αναπαραγώγιμα αποτελέσματα. Στο Κουφόβουνο οκτώ από τους είκοσι σκελετούς, που εξετάστηκαν, έδωσαν στοιχεία για μιτοχονδρνακό ή/και πυρηνικό DNA, ενώ στον Ταφικό Κύκλο Β των Μυκηνών ενδείξεις για μιτοχονδριακό DNA έδωσαν τέσσερεις από τους είκοσι δύο σκελετούς, που μελετήθηκαν. Σε δύο περιπτώσεις επιβεβαιώθηκε η ένδειξη στενής συγγένειας, κάτι το οποίο είχε ήδη προταθεί με την αποκατάσταση των προσώπων: το γεγονός αυτό εγείρει ενδιαφέροντα ερωτήματα σχετικά με τις κοινωνικές σχέσεις και το ρόλο γυναικών υψηλής κοινωνικής στάθμης στην κοινωνία της Μέσης και της Ύστερης Εποχής του Χαλκού. Συμπεραίνουμε ότι, αν και μπορεί να αναγνωριστεί DNA σε ορισμένους σκελετούς της Ανατολικής Μεσογείου των τελευταίων αιώνων της Εποχής του Χαλκού, δεν εντοπίζεται συχνά σε υλικό αυτής της εποχής και ενδεχομένως απουσιάζει από παλαιότερο υλνκό.</jats:p

Pulmonary retention of primed neutrophils: a novel protective host response, which is impaired in the acute respiratory distress syndrome.

RATIONALE: Acute respiratory distress syndrome (ARDS) affects over 200000 people annually in the USA. Despite causing severe, and often refractory, hypoxaemia, the high mortality and long-term morbidity of ARDS results mainly from extra-pulmonary organ failure; however the mechanism for this organ crosstalk has not been determined. METHODS: Using autologous radiolabelled neutrophils we investigated the pulmonary transit of primed and unprimed neutrophils in humans. Flow cytometry of whole blood samples was used to assess transpulmonary neutrophil priming gradients in patients with ARDS, sepsis and perioperative controls. MAIN RESULTS: Unprimed neutrophils passed through the lungs with a transit time of 14.2 s, only 2.3 s slower than erythrocytes, and with <5% first-pass retention. Over 97% of neutrophils primed ex vivo with granulocyte macrophage colony-stimulating factor were retained on first pass, with 48% still remaining in the lungs at 40 min. Neutrophils exposed to platelet-activating factor were initially retained but subsequently released such that only 14% remained in the lungs at 40 min. Significant transpulmonary gradients of neutrophil CD62L cell surface expression were observed in ARDS compared with perioperative controls and patients with sepsis. CONCLUSIONS: We demonstrated minimal delay and retention of unprimed neutrophils transiting the healthy human pulmonary vasculature, but marked retention of primed neutrophils; these latter cells then 'deprime' and are re-released into the systemic circulation. Further, we show that this physiological depriming mechanism may fail in patients with ARDS, resulting in increased numbers of primed neutrophils within the systemic circulation. This identifies a potential mechanism for the remote organ damage observed in patients with ARDS.This work was supported by the Wellcome Trust, MRC (UK), Papworth Hospital R&D, Intensive Care Society and NIHR Cambridge Biomedical Research Centre.This is the final published version, also available from http://thorax.bmj.com/content/early/2014/04/04/thoraxjnl-2013-204742.full

In vivo imaging of hepatic neutrophil migration in severe alcoholic hepatitis with 111In-radiolabelled leucocytes.

The study's aim was to image severe alcoholic hepatitis (SAH) using 111In-labelled leucocytes with two objectives in mind: firstly for non-invasive diagnosis and secondly to provide a platform for experimental therapies aiming to inhibit intrahepatic neutrophil migration. 111In-leucocyte scintigraphy was performed 30 min and 24 h post-injection in 19 patients with SAH, 14 abstinent patients with alcohol-related cirrhosis and 11 normal controls. Eleven with SAH and seven with cirrhosis also had 99mTc-nanocolloid scintigraphy. Change in hepatic 111In radioactivity was expressed as decay-corrected 24 h:30 min count ratio and, in SAH, compared with histological grading of steatohepatitis and expression of granulocyte marker, CD15. Hepatic microautoradiography on biopsy specimens obtained 24 h post-injection of 111In-leucocytes was performed in one patient. Median 24 h:30 min hepatic 111In activity ratio was higher in SAH (2.5 (interquartile range (IQR): 1.7-4.0) compared with cirrhotics and normal controls (1.0 (0.8-1.1) and 0.8 (0.7-0.9) respectively, P<0.0001). In SAH, it correlated with CD15 expression (r = 0.62, P=0.023) and was higher in marked compared with mild/moderate steatohepatitis (4.0 (3.0-4.6) compared with 1.8 (1.5-2.6), P=0.006). Hepatic-to-splenic 99mTc count rate ratio was reduced in SAH (0.5 (0.4-1.4)) compared with cirrhotics (2.3( 0.6-3.0)) and three historic normal controls (4.2 (3.8-5.0); P=0.003), consistent with impaired hepatic reticuloendothelial function. Scintigraphic findings in SAH included prominent lung radioactivity at 30 min, likely the result of neutrophil primimg. Microautoradiography demonstrated cell-associated 111In in areas of parenchymal neutrophil infiltration. In conclusion, 111In-leucocyte scintigraphy can non-invasively diagnose SAH and could provide a platform for evaluation of novel treatments aiming to inhibit intrahepatic neutrophil migration.The study was funded by a project grant from Brighton and Sussex Medical Schoo