Plasma appearance and disappearance of an oral dose of 25-hydroxyvitamin D2 in healthy adults

25-Hydroxyvitamin D (25(OH)D) half-life is a potential biomarker for investigating vitamin D metabolism and requirements. We performed a pilot study to assess the approach and practical feasibility of measuring 25(OH)D half-life after an oral dose. A total of twelve healthy Gambian men aged 18–23 years were divided into two groups to investigate the rate and timing of (1) absorption and (2) plasma disappearance after an 80 nmol oral dose of 25(OH)D2. Fasting blood samples were collected at baseline and, in the first group, every 2 h post-dose for 12 h, at 24 h, 48 h and on day 15. In the second group, fasting blood samples were collected on days 3, 4, 5, 6, 9, 12, 15, 18 and 21. Urine was collected for 2 h after the first morning void at baseline and on day 15. 25(OH)D2 plasma concentration was measured by ultra-performance liquid chromatography-tandem MS/MS and corrected for baseline. Biomarkers of vitamin D, Ca and P metabolism were measured at baseline and on day 15. The peak plasma concentration of 25(OH)D2 was 9·6 (sd 0·9) nmol/l at 4·4 (sd 1·8) h. The terminal slope of 25(OH)D2 disappearance was identified to commence from day 6. The terminal half-life of plasma 25(OH)D2 was 13·4 (sd 2·7) d. There were no significant differences in plasma 25(OH)D3, total 1,25(OH)2D, parathyroid hormone, P, Ca and ionised Ca and urinary Ca and P between baseline and day 15 and between the two groups. The present study provides data on the plasma response to oral 25(OH)D2 that will underpin and contribute to the further development of studies to investigate 25(OH)D half-life

Are social innovation paradigms incommensurable?

This paper calls attention to the problematic use of the concept of social innovation which remains undefined despite its proliferation throughout academic and policy discourses. Extant research has thus far failed to capture the socio-political contentions which surround social innovation. This paper therefore draws upon the work of Thomas Kuhn and conducts a paradigmatic analysis of the field of social innovation which identifies two emerging schools: one technocratic, the other democratic. The paper identifies some of the key thinkers in each paradigm and explains how the struggle between these two paradigms reveals itself to be part of a broader conflict between neoliberalism and it opponents and concludes by arguing that future research focused upon local contextualised struggles will reveal which paradigm is in the ascendancy

Thrombin promotes diet-induced obesity through fibrin-driven inflammation

Obesity promotes a chronic inflammatory and hypercoagulable state that drives cardiovascular disease, type 2 diabetes, fatty liver disease, and several cancers. Elevated thrombin activity underlies obesity-linked thromboembolic events, but the mechanistic links between the thrombin/fibrin(ogen) axis and obesity-associated pathologies are incompletely understood. In this work, immunohistochemical studies identified extravascular fibrin deposits within white adipose tissue and liver as distinct features of mice fed a high-fat diet (HFD) as well as obese patients. Fibγ390–396A mice carrying a mutant form of fibrinogen incapable of binding leukocyte αMβ2-integrin were protected from HFD-induced weight gain and elevated adiposity. Fibγ390–396A mice had markedly diminished systemic, adipose, and hepatic inflammation with reduced macrophage counts within white adipose tissue, as well as near-complete protection from development of fatty liver disease and glucose dysmetabolism. Homozygous thrombomodulin-mutant ThbdPro mice, which have elevated thrombin procoagulant function, gained more weight and developed exacerbated fatty liver disease when fed a HFD compared with WT mice. In contrast, treatment with dabigatran, a direct thrombin inhibitor, limited HFD-induced obesity development and suppressed progression of sequelae in mice with established obesity. Collectively, these data provide proof of concept that targeting thrombin or fibrin(ogen) may limit pathologies in obese patients

Rethinking Radical Democracy

Over the course of three decades, vocabularies of radical democracy have pressed their stamp on democratic thought. Trading on the intuition that there is more to democracy than elections, they have generated critical insights into the important role that practices of pluralisation and critique play in bettering institutional politics. As a result, few would today deny the radical democratic contribution to democratic thought. What many might question, however, is its continuing traction. The paper probes this question, focusing on the nuanced place of democracy in contemporary radical work. It grapples with the difficulties that this poses for radical democrats and it suggests that a way of overcoming these difficulties – that threaten to undermine the coherence of radical democracy – is to rethink and reconstruct the distinctiveness of its vocabulary. The paper attempts such a reconstruction. It develops the idea of the promissory rule of the many and it discusses the ways it rejuvenates broader democratic thought

Measuring coverage in MNCH: indicators for global tracking of newborn care.

Neonatal mortality accounts for 43% of under-five mortality. Consequently, improving newborn survival is a global priority. However, although there is increasing consensus on the packages and specific interventions that need to be scaled up to reduce neonatal mortality, there is a lack of clarity on the indicators needed to measure progress. In 2008, in an effort to improve newborn survival, the Newborn Indicators Technical Working Group (TWG) was convened by the Saving Newborn Lives program at Save the Children to provide a forum to develop the indicators and standard measurement tools that are needed to measure coverage of key newborn interventions. The TWG, which included evaluation and measurement experts, researchers, individuals from United Nations agencies and non-governmental organizations, and donors, prioritized improved consistency of measurement of postnatal care for women and newborns and of immediate care behaviors and practices for newborns. In addition, the TWG promoted increased data availability through inclusion of additional questions in nationally representative surveys, such as the United States Agency for International Development-supported Demographic and Health Surveys and the United Nations Children's Fund-supported Multiple Indicator Cluster Surveys. Several studies have been undertaken that have informed revisions of indicators and survey tools, and global postnatal care coverage indicators have been finalized. Consensus has been achieved on three additional indicators for care of the newborn after birth (drying, delayed bathing, and cutting the cord with a clean instrument), and on testing two further indicators (immediate skin-to-skin care and applications to the umbilical cord). Finally, important measurement gaps have been identified regarding coverage data for evidence-based interventions, such as Kangaroo Mother Care and care seeking for newborn infection

Count every newborn; a measurement improvement roadmap for coverage data.

BACKGROUND: The Every Newborn Action Plan (ENAP), launched in 2014, aims to end preventable newborn deaths and stillbirths, with national targets of ≤12 neonatal deaths per 1000 live births and ≤12 stillbirths per 1000 total births by 2030. This requires ambitious improvement of the data on care at birth and of small and sick newborns, particularly to track coverage, quality and equity. METHODS: In a multistage process, a matrix of 70 indicators were assessed by the Every Newborn steering group. Indicators were graded based on their availability and importance to ENAP, resulting in 10 core and 10 additional indicators. A consultation process was undertaken to assess the status of each ENAP core indicator definition, data availability and measurement feasibility. Coverage indicators for the specific ENAP treatment interventions were assigned task teams and given priority as they were identified as requiring the most technical work. Consultations were held throughout. RESULTS: ENAP published 10 core indicators plus 10 additional indicators. Three core impact indicators (neonatal mortality rate, maternal mortality ratio, stillbirth rate) are well defined, with future efforts needed to focus on improving data quantity and quality. Three core indicators on coverage of care for all mothers and newborns (intrapartum/skilled birth attendance, early postnatal care, essential newborn care) have defined contact points, but gaps exist in measuring content and quality of the interventions. Four core (antenatal corticosteroids, neonatal resuscitation, treatment of serious neonatal infections, kangaroo mother care) and one additional coverage indicator for newborns at risk or with complications (chlorhexidine cord cleansing) lack indicator definitions or data, especially for denominators (population in need). To address these gaps, feasible coverage indicator definitions are presented for validity testing. Measurable process indicators to help monitor health service readiness are also presented. A major measurement gap exists to monitor care of small and sick babies, yet signal functions could be tracked similarly to emergency obstetric care. CONCLUSIONS: The ENAP Measurement Improvement Roadmap (2015-2020) outlines tools to be developed (e.g., improved birth and death registration, audit, and minimum perinatal dataset) and actions to test, validate and institutionalise proposed coverage indicators. The roadmap presents a unique opportunity to strengthen routine health information systems, crosslinking these data with civil registration and vital statistics and population-based surveys. Real measurement change requires intentional transfer of leadership to countries with the greatest disease burden and will be achieved by working with centres of excellence and existing networks

Toolbox for Non-Intrusive Structural and Functional Analysis of Recombinant VLP Based Vaccines: A Case Study with Hepatitis B Vaccine

Background: Fundamental to vaccine development, manufacturing consistency, and product stability is an understanding of the vaccine structure-activity relationship. With the virus-like particle (VLP) approach for recombinant vaccines gaining popularity, there is growing demand for tools that define their key characteristics. We assessed a suite of non-intrusive VLP epitope structure and function characterization tools by application to the Hepatitis B surface antigen (rHBsAg) VLP-based vaccine. Methodology: The epitope-specific immune reactivity of rHBsAg epitopes to a given monoclonal antibody was monitored by surface plasmon resonance (SPR) and quantitatively analyzed on rHBsAg VLPs in-solution or bound to adjuvant with a competitive enzyme-linked immunosorbent assay (ELISA). The structure of recombinant rHBsAg particles was examined by cryo transmission electron microscopy (cryoTEM) and in-solution atomic force microscopy (AFM). Principal Findings: SPR and competitive ELISA determined relative antigenicity in solution, in real time, with rapid turnaround, and without the need of dissolving the particulate aluminum based adjuvant. These methods demonstrated the nature of the clinically relevant epitopes of HBsAg as being responsive to heat and/or redox treatment. In-solution AFM and cryoTEM determined vaccine particle size distribution, shape, and morphology. Redox-treated rHBsAg enabled 3D reconstruction from CryoTEM images – confirming the previously proposed octahedral structure and the established lipidto-protei

Revolution from above in English schools: neoliberalism, the democratic commons and education

The ideas of the New Left and the recently emerged alter-globalisation movements are marginal within current policy debates concerning the English education system. Here I seek to demonstrate the interconnections between the New Left and the alter-globalisation movement and suggest that these ideas contain a powerful corrective to the increasingly authoritarian present. The next part of the article considers the development of neoliberalism both in a theoretical context and since the arrival of the new Conservative–Liberal government in the UK. Here I outline the rapid transformation of English schools under the academies programme and look at how it has been explicitly linked to ideas of ‘moral collapse’ evident in the popular discourse of ‘Broken Britain’. Especially significant in this respect has been the labelling of comprehensive schools as ‘failures’ and the explicit imposition of more authoritarian understandings of pedagogy. I seek to explore both the rapidity of this transformation in the context of the dissatisfaction with the idea of comprehensive schools shown by the political Right and the Third Way’s reworking of socialism. Finally I briefly consider more progressive alternatives for schools and education by returning to the idea of the democratic commons. In this respect, the cultural Left needs to explore more radical alternatives beyond the defence of comprehensive schooling which sounds both nostalgic and misplaced within our global times