An analysis of National Health Service Trust websites on the occupational backgrounds of 'Non-Executive Directors' on England's Acute Trusts.

OBJECTIVES: To explore the occupational backgrounds of English Non-Executive Directors (NED) on Acute National Health Service (NHS) Trusts. DESIGN: Data extrapolated from Trust websites of NED' occupational backgrounds by gender and occupations, and inter-rater reliability test undertaken. SETTING: Data were available on all but 24 of the 166 Acute Trusts' from all regions. PARTICIPANTS: Trust Chairs and NED were categorised by their dominant occupation. MAIN OUTCOME MEASURE: Differentiating NED with and without health or social care leadership experience. RESULTS: The ratings of NED' occupations positively correlated (p < 0.001). Occupational categories were Commerce and Finance from private and public sectors or with Medical or Community leadership experience. Only 4% of Chairs were Medical, 2% from Community - the majority (61%) from Commerce and Finance. Of the 1001 NED, 8% and 6% respectively had Medical or Community leadership experience; most (86%) were Commerce, Finance and non-clinical Managerial backgrounds. Females made up 27% of NED. CONCLUSIONS: With a predominance of Chairs and NED without health or social care leadership experience, are current Boards equipped to avoid inadvertently 'doing the system's business' (Francis, 2013) rather than developing a more patient-centred, clinically led and integrated NHS? It is suggested that Boards need more NED with health and social care leadership experience and methods to identify the 'patient's agenda' to create 'a common culture' that places 'patients at the centre of everything we do' (Hunt, 2012). A key context for Trust Boards operations is funding, which Francis' terms of reference excluded, an issue that is briefly discussed

The End of Fossil Fuel Era: Supply-demand Measures through Energy Efficiency

4th International Conference on Sustainable Future for Human Security, SustaiN 2013In the last ten years, the world has faced an uncertain oil prices, unlike during 1970 when the oil crisis occurred due to the Middle East political crisis. The problem now facing has more in the increases of oil demand when the developed countries are not the major consumers for oil and other major fossil fuel anymore. China, India, Brazil and South East Asia nations lead the increases of the energy demand inline with their economic growth and population domination. The energy demand in ASEAN is dominated by the countries in Malaya peninsula (cognate) such as Indonesia and Malaysia (225 million and 25 million population respectively), Singapore and Brunei lead the domination in the economics, which are also one of the variables of the increases of energy demand. The paper will estimate the future energy demand (includes fossil fuel) ASEAN by using bottom up approach and various variables such as economic development and population trend from references developed countries, the country's landscape and technological efficiency. It shows that the energy demand increase for the region is inevitable, the increases are followed by some consequences such as local fossil fuel scarcity, technological boundaries and infrastructure adjustment. The efficiency is most likely to be one of the keys for the region to be survived in the next 5 to 6 decades

U-box E3 ubiquitin ligase PUB17 acts in the nucleus to promote specific immune pathways triggered by Phytophthora infestans

Ubiquitination regulates many processes in plants, including immunity. The E3 ubiquitin ligase PUB17 is a positive regulator of programmed cell death (PCD) triggered by resistance proteins CF4/9 in tomato. Its role in immunity to the potato late blight pathogen, Phytophthora infestans, was investigated here. Silencing StPUB17 in potato by RNAi and NbPUB17 in Nicotiana benthamiana by virus-induced gene silencing (VIGS) each enhanced P. infestans leaf colonization. PAMP-triggered immunity (PTI) transcriptional responses activated by flg22, and CF4/Avr4-mediated PCD were attenuated by silencing PUB17. However, silencing PUB17 did not compromise PCD triggered by P. infestans PAMP INF1, or co-expression of R3a/AVR3a, demonstrating that not all PTI- and PCD-associated responses require PUB17. PUB17 localizes to the plant nucleus and especially in the nucleolus. Transient over-expression of a dominant-negative StPUB17V314I,V316I mutant, which retained nucleolar localization, suppressed CF4-mediated cell death and enhanced P. infestans colonization. Exclusion of the StPUB17V314I,V316I mutant from the nucleus abolished its dominant-negative activity, demonstrating that StPUB17 functions in the nucleus. PUB17 is a positive regulator of immunity to late blight that acts in the nucleus to promote specific PTI and PCD pathways

Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state

Human respiratory syncytial virus (RSV) is the main cause of lower respiratory tract infections in young children. The RSV fusion protein (F) is highly conserved and is the only viral membrane protein that is essential for infection. The prefusion conformation of RSV F is considered the most relevant target for antiviral strategies because it is the fusion-competent form of the protein and the primary target of neutralizing activity present in human serum. Here, we describe two llama-derived single-domain antibodies (VHHs) that have potent RSV-neutralizing activity and bind selectively to prefusion RSV F with picomolar affinity. Crystal structures of these VHHs in complex with prefusion F show that they recognize a conserved cavity formed by two F protomers. In addition, the VHHs prevent RSV replication and lung infiltration of inflammatory monocytes and T cells in RSV-challenged mice. These prefusion F-specific VHHs represent promising antiviral agents against RSV

A Study to Validate a Self-Reported Version of the ONS Drug Dependence Questionnaire

Aim: A prospective study to establish the reliability of a self-completion version of the Office for National Statistics (ONS) questionnaire for assessing drug dependence of substance misuse clients. Method: A total of 47 treatment seeking opioid-dependent clients completed the self-complete version of the ONS questionnaire (ONS-sc) followed by the interviewer-administered ONS questionnaire (ONS-ia) at a single clinic appointment. Scores for four Class A drugs (heroin, methadone, speed and crack/cocaine) from both formats were compared. Results: The observed agreement was 87% or more and Cohen's kappa was 0.7 (p < 0.001) or more for all four Class A drugs. Sensitivity for each Class A drugs was 56% or higher and specificity was 87% or higher. Sensitivity for severe heroin dependency was 98% (CI 89–100%). There was a 100% correlation between the ONS-sc and positive urine analysis for heroin use. However, methadone and crack/cocaine drug use appeared under reported. Conclusion: ONS-sc is a feasible, practical and time-saving alternative to a detailed interview on drug dependence. Further research with a larger sample size and non-opiate-dependent clients are needed, as this could prove a useful tool for monitoring clients in everyday practice, or for survey purposes where interviews are impractical

Neutralization of Diverse Human Cytomegalovirus Strains Conferred by Antibodies Targeting Viral gH/gL/pUL128-131 Pentameric Complex

Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection, and developing a prophylactic vaccine is of high priority to public health. We recently reported a replication-defective human cytomegalovirus with restored pentameric complex glycoprotein H (gH)/gL/pUL128-131 for prevention of congenital HCMV infection. While the quantity of vaccine-induced antibody responses can be measured in a viral neutralization assay, assessing the quality of such responses, including the ability of vaccine-induced antibodies to cross-neutralize the field strains of HCMV, remains a challenge. In this study, with a panel of neutralizing antibodies from three healthy human donors with natural HCMV infection or a vaccinated animal, we mapped eight sites on the dominant virus-neutralizing antigen-the pentameric complex of glycoprotein H (gH), gL, and pUL128, pUL130, and pUL131. By evaluating the site-specific antibodies in vaccine immune sera, we demonstrated that vaccination elicited functional antiviral antibodies to multiple neutralizing sites in rhesus macaques, with quality attributes comparable to those of CMV hyperimmune globulin. Furthermore, these immune sera showed antiviral activities against a panel of genetically distinct HCMV clinical isolates. These results highlighted the importance of understanding the quality of vaccine-induced antibody responses, which includes not only the neutralizing potency in key cell types but also the ability to protect against the genetically diverse field strains. IMPORTANCE HCMV is the leading cause of congenital viral infection, and development of a preventive vaccine is a high public health priority. To understand the strain coverage of vaccine-induced immune responses in comparison with natural immunity, we used a panel of broadly neutralizing antibodies to identify the immunogenic sites of a dominant viral antigen-the pentameric complex. We further demonstrated that following vaccination of a replication-defective virus with the restored pentameric complex, rhesus macaques can develop broadly neutralizing antibodies targeting multiple immunogenic sites of the pentameric complex. Such analyses of site-specific antibody responses are imperative to our assessment of the quality of vaccine-induced immunity in clinical studies