Intravenous multipotent adult progenitor cell therapy after traumatic brain injury: modulation of the resident microglia population

INTRODUCTION: We have demonstrated previously that the intravenous delivery of multipotent adult progenitor cells (MAPC) after traumatic brain injury affords neuroprotection via interaction with splenocytes, leading to an increase in systemic anti-inflammatory cytokines. We hypothesize that the observed modulation of the systemic inflammatory milieu is related to T regulatory cells and a subsequent increase in the locoregional neuroprotective M2 macrophage population. METHODS: C57B6 mice were injected with intravenous MAPC 2 and 24 hours after controlled cortical impact injury. Animals were euthanized 24, 48, 72, and 120 hours after injury. In vivo, the proportion of CD4(+)/CD25(+)/FOXP3(+) T-regulatory cells were measured in the splenocyte population and plasma. In addition, the brain CD86(+) M1 and CD206(+) M2 macrophage populations were quantified. A series of in vitro co-cultures were completed to investigate the need for direct MAPC:splenocyte contact as well as the effect of MAPC therapy on M1 and M2 macrophage subtype apoptosis and proliferation. RESULTS: Significant increases in the splenocyte and plasma T regulatory cell populations were observed with MAPC therapy at 24 and 48 hours, respectively. In addition, MAPC therapy was associated with an increase in the brain M2/M1 macrophage ratio at 24, 48 and 120 hours after cortical injury. In vitro cultures of activated microglia with supernatant derived from MAPC:splenocyte co-cultures also demonstrated an increase in the M2/M1 ratio. The observed changes were secondary to an increase in M1 macrophage apoptosis. CONCLUSIONS: The data show that the intravenous delivery of MAPC after cortical injury results in increases in T regulatory cells in splenocytes and plasma with a concordant increase in the locoregional M2/M1 macrophage ratio. Direct contact between the MAPC and splenocytes is required to modulate activated microglia, adding further evidence to the central role of the spleen in MAPC-mediated neuroprotection

A New Tool for CME Arrival Time Prediction using Machine Learning Algorithms: CAT-PUMA

Coronal mass ejections (CMEs) are arguably the most violent eruptions in the solar system. CMEs can cause severe disturbances in interplanetary space and can even affect human activities in many aspects, causing damage to infrastructure and loss of revenue. Fast and accurate prediction of CME arrival time is vital to minimize the disruption that CMEs may cause when interacting with geospace. In this paper, we propose a new approach for partial-/full halo CME Arrival Time Prediction Using Machine learning Algorithms (CAT-PUMA). Via detailed analysis of the CME features and solar-wind parameters, we build a prediction engine taking advantage of 182 previously observed geo-effective partial-/full halo CMEs and using algorithms of the Support Vector Machine. We demonstrate that CAT-PUMA is accurate and fast. In particular, predictions made after applying CAT-PUMA to a test set unknown to the engine show a mean absolute prediction error of ∼5.9 hr within the CME arrival time, with 54% of the predictions having absolute errors less than 5.9 hr. Comparisons with other models reveal that CAT-PUMA has a more accurate prediction for 77% of the events investigated that can be carried out very quickly, i.e., within minutes of providing the necessary input parameters of a CME. A practical guide containing the CAT-PUMA engine and the source code of two examples are available in the Appendix, allowing the community to perform their own applications for prediction using CAT-PUMA

Appraisal of literature reviews on end-of-life care for minority ethnic groups in the UK and a critical comparison with policy recommendations from the UK end-of-life care strategy

<p>Abstract</p> <p>Background</p> <p>Evidence of low end-of-life (EoL) care service use by minority ethnic groups in the UK has given rise to a body of research and a number of reviews of the literature. This article aims to review and evaluate literature reviews on minority ethnic groups and EoL care in the UK and assess their suitability as an evidence base for policy.</p> <p>Methods</p> <p>Systematic review. Searches were carried out in thirteen electronic databases, eight journals, reference lists, and grey literature. Reviews were included if they concerned minority ethnic groups and EoL care in the UK. Reviews were graded for quality and key themes identified.</p> <p>Results</p> <p>Thirteen reviews (2001-2009) met inclusion criteria. Seven took a systematic approach, of which four scored highly for methodological quality (a mean score of six, median seven). The majority of systematic reviews were therefore of a reasonable methodological quality. Most reviews were restricted by ethnic group, aspect of EoL care, or were broader reviews which reported relevant findings. Six key themes were identified.</p> <p>Conclusions</p> <p>A number of reviews were systematic and scored highly for methodological quality. These reviews provide a good reflection of the primary evidence and could be used to inform policy. The complexity and inter-relatedness of factors leading to low service use was recognised and reflected in reviews' recommendations for service improvement. Recommendations made in the UK End-of-Life Care Strategy were limited in comparison, and the Strategy's evidence base concerning minority ethnic groups was found to be narrow. Future policy should be embedded strongly in the evidence base to reflect the current literature and minimise bias.</p

Suicide and Suicide Risk in Lesbian, Gay, Bisexual, and Transgender Populations: Review and Recommendations

Despite strong indications of elevated risk of suicidal behavior in lesbian, gay, bisexual, and transgender people, limited attention has been given to research, interventions or suicide prevention programs targeting these populations. This article is a culmination of a three-year effort by an expert panel to address the need for better understanding of suicidal behavior and suicide risk in sexual minority populations, and stimulate the development of needed prevention strategies, interventions and policy changes. This article summarizes existing research findings, and makes recommendations for addressing knowledge gaps and applying current knowledge to relevant areas of suicide prevention practice

Mechanical characterisation of polymer of intrinsic microporosity PIM-1 for hydrogen storage applications

Polymers of intrinsic microporosity (PIMs) are currently attracting interest due to their unusual combination of high surface areas and capability to be processed into free-standing films. However, there has been little published work with regards to their physical and mechanical properties. In this paper, detailed characterisation of PIM-1 was performed by considering its chemical, gas adsorption and mechanical properties. The polymer was cast into films, and characterised in terms of their hydrogen adsorption at −196 °C up to much higher pressures (17 MPa) than previously reported (2 MPa), demonstrating the maximum excess adsorbed capacity of the material and its uptake behaviour in higher pressure regimes. The measured tensile strength of the polymer film was 31 MPa with a Young’s modulus of 1.26 GPa, whereas the average storage modulus exceeded 960 MPa. The failure strain of the material was 4.4%. It was found that the film is thermally stable at low temperatures, down to −150 °C, and decomposition of the material occurs at 350 °C. These results suggest that PIM-1 has sufficient elasticity to withstand the elastic deformations occurring within state-of-the-art high-pressure hydrogen storage tanks and sufficient thermal stability to be applied at the range of temperatures necessary for gas storage applications

A prospective, multi-method, multi-disciplinary, multi-level, collaborative, social-organisational design for researching health sector accreditation [LP0560737]

BACKGROUND: Accreditation has become ubiquitous across the international health care landscape. Award of full accreditation status in health care is viewed, as it is in other sectors, as a valid indicator of high quality organisational performance. However, few studies have empirically demonstrated this assertion. The value of accreditation, therefore, remains uncertain, and this persists as a central legitimacy problem for accreditation providers, policymakers and researchers. The question arises as to how best to research the validity, impact and value of accreditation processes in health care. Most health care organisations participate in some sort of accreditation process and thus it is not possible to study its merits using a randomised controlled strategy. Further, tools and processes for accreditation and organisational performance are multifaceted. METHODS/DESIGN: To understand the relationship between them a multi-method research approach is required which incorporates both quantitative and qualitative data. The generic nature of accreditation standard development and inspection within different sectors enhances the extent to which the findings of in-depth study of accreditation process in one industry can be generalised to other industries. This paper presents a research design which comprises a prospective, multi-method, multi-level, multi-disciplinary approach to assess the validity, impact and value of accreditation. DISCUSSION: The accreditation program which assesses over 1,000 health services in Australia is used as an exemplar for testing this design. The paper proposes this design as a framework suitable for application to future international research into accreditation. Our aim is to stimulate debate on the role of accreditation and how to research it.Jeffrey Braithwaite, Johanna Westbrook, Marjorie Pawsey, David Greenfield, Justine Naylor, Rick Iedema, Bill Runciman, Sally Redman, Christine Jorm, Maureen Robinson, Sally Nathan and Robert Gibber