Embedded expert system for space shuttle main engine maintenance

The SPARTA Embedded Expert System (SEES) is an intelligent health monitoring system that directs analysis by placing confidence factors on possible engine status and then recommends a course of action to an engineer or engine controller. The technique can prevent catastropic failures or costly rocket engine down time because of false alarms. Further, the SEES has potential as an on-board flight monitor for reusable rocket engine systems. The SEES methodology synergistically integrates vibration analysis, pattern recognition and communications theory techniques with an artificial intelligence technique - the Embedded Expert System (EES)

Induction of human immunodeficiency virus type 1-specific T cells by a bluetongue virus tubule-vectored vaccine prime-recombinant modified virus Ankara boost regimen.

In the absence of strategies for reliable induction of antibodies broadly neutralizing human immunodeficiency virus type 1 (HIV-1), vaccine efforts have shifted toward the induction of cell-mediated immunity. Here we describe the construction and immunogenicity of novel T-cell vaccine NS1.HIVA, which delivers the HIV-1 clade A consensus-derived immunogen HIVA on the surface of tubular structures spontaneously formed by protein NS1 of bluetongue virus. We demonstrated that NS1 tubules can accommodate a protein as large as 527 amino acids without losing their self-assembly capability. When injected into BALB/c mice by several routes, chimeric NS1.HIVA tubules induced HIV-1-specific major histocompatibility complex class I-restricted T cells. These could be boosted by modified virus Ankara expressing the same immunogen and generate a memory capable of gamma interferon (IFN-gamma) production, proliferation, and lysis of sensitized target cells. Induced memory T cells readily produced IFN-gamma 230 days postimmunization, and upon a surrogate virus challenge, NS1.HIVA vaccine alone decreased the vaccinia virus vv.HIVA load in ovaries by 2 orders of magnitude 280 days after immunization. Thus, because of its T-cell immunogenicity and antigenic simplicity, the NS1 delivery system could serve as a priming agent for heterologous prime-boost vaccination regimens. Its usefulness in primates, including humans, remains to be determined

The consensual politics of development: a case study of hydropower development in the eastern Himalayan region of India

Criticism and contestation of large dam projects have a long, strong history in India. In this paper, we analyze diverse civil-society responses to large dam projects in the Eastern Himalaya region of India, which has in the past decades been presented as a clean, green, climate-mitigating way of generating energy, but critiqued for its adverse impacts more recently. We draw our findings primarily based on interviews with NGOs involved in environmental and/or water issues in Darjeeling, interviews with those involved in a local people’s movement ‘Affected Citizens of Teesta’, and participatory research over the course of three years between 2015 and 2018. Our findings show how doing development for the state, the market and/or donor organizations compromises the ability of NGOs in the Darjeeling region to hold these actors accountable for social and environmental excesses. In the same region, dam projects in North Sikkim led to a local people’s movement, where expressions of indigeneity, identity and place were used to critique and contest the State’s agenda of development, in ways that were symptomatically different to NGOs tied down by relations of developmental bureaucracy. Our findings reveal how the incursion of State authority, presence and power in civil-society undermines the civil society mandate of transformative social change, and additionally, how the geographical, political, institutional and identity-based divides that fragment diverse civil-society institutions and actors make it challenging to counter the increasingly consensual politics of environmental governance

Epidemiology of blindness in children

An estimated 1.4 million of the world’s children are blind. A blind child is more likely to live in socioeconomic deprivation, to be more frequently hospitalised during childhood and to die in childhood than a child not living with blindness. This update of a previous review on childhood visual impairment focuses on emerging therapies for children with severe visual disability (severe visual impairment and blindness or SVI/BL). For children in higher income countries, cerebral visual impairment and optic nerve anomalies remain the most common causes of SVI/BL, while retinopathy of prematurity (ROP) and cataract are now the most common avoidable causes. The constellation of causes of childhood blindness in lower income settings is shifting from infective and nutritional corneal opacities and congenital anomalies to more resemble the patterns seen in higher income settings. Improvements in maternal and neonatal health and investment in and maintenance of national ophthalmic care infrastructure are the key to reducing the burden of avoidable blindness. New therapeutic targets are emerging for childhood visual disorders, although the safety and efficacy of novel therapies for diseases such as ROP or retinal dystrophies are not yet clear. Population-based epidemiological research, particularly on cerebral visual impairment and optic nerve hypoplasia, is needed in order to improve understanding of risk factors and to inform and support the development of novel therapies for disorders currently considered ‘untreatable’

Visual impairment, severe visual impairment, and blindness in children in Britain (BCVIS2): a national observational study

Background: The WHO VISION 2020 global initiative against blindness, launched in 2000, prioritised childhood visual disability by aiming to end avoidable childhood blindness by 2020. However, progress has been hampered by the global paucity of epidemiological data concerning childhood visual disability. The British Childhood Visual Impairment and Blindness Study 2 (BCVIS2) was done to address this evidence gap. Methods: BCVIS2 was a prospective UK-wide, cross-sectional, observational study to establish an inception cohort of children newly diagnosed with visual impairment. Ophthalmologists and paediatricians reported cases from 89 hospitals and community centres across the UK. We included children aged 18 years or younger who were newly diagnosed with any condition causing impaired visual acuity to a level of 0·5 logMAR or worse (worse than 6/18 Snellen) in each eye, or equivalent vision as assessed by standard qualitative measures, between Oct 1, 2015, and Nov 1, 2016. Eligible children were notified simultaneously but independently by their managing ophthalmologists and paediatricians via the two national active surveillance schemes, the British Ophthalmological Surveillance Unit and the British Paediatric Surveillance Unit. Standardised detailed demographic, socioeconomic, and clinical data about detection, management, and treatment were collected at diagnosis and 1 year later. We calculated incidence estimates and relative rates by key sociodemographic factors. We did descriptive analyses of underlying ophthalmic disorders and non-ophthalmic comorbidities. Findings: 61 (7%) of 845 eligible children initially notified were ineligible at follow-up because of improved vision after treatment. Thus, the study sample comprised 784 children with permanent newly-diagnosed all-cause visual impairment, severe visual impairment, or blindness. 559 (72%) of 778 children had clinically significant non-ophthalmic impairments or conditions. 28 (4%) of 784 children died within a year after diagnosis of visual disability (all had underlying systemic disorders). Incidence of visual disability in the first year of life was 5·19 per 10 000 children (95% CI 4·71–5·72), almost ten times higher than among 1-to-4-year-olds and between 20 times and 100 times higher than in the older age groups. The overall cumulative incidence (or lifetime risk) of visual impairment, severe visual impairment, or blindness was 10·03 per 10 000 children (9·35–10·76). Incidence rates were higher for those from any ethnic minority group, the lowest quintile of socioeconomic status, and those born preterm or with low birthweight. 345 (44%) of 784 children had a single affected anatomical site. Disorders of the brain and visual pathways affected 378 (48%) of 784 children. Interpretation: BCVIS2 provides a contemporary snapshot of the heterogeneity, multi-morbidity, and vulnerability associated with childhood visual disability in a high-income country. These findings could facilitate developing and delivering health care and planning of interventional research. Our findings highlight the importance of including childhood visual disability as a sentinel event and metric in global child health initiatives. Funding: Fight for Sight, National Institute for Health Research, and Ulverscroft Foundation

Microbiological findings and prescribing trends in SARS- CoV-2 positive patients in two United Kingdom Hospitals

Objective: To describe antibiotic prescribing and microbiological findings in patients admitted to two London hospitals with COVID-19. Methods: This is a retrospective review of confirmed SARS-CoV-2 infected adults admitted between 9th February and 10th May 2020. Demographics, critical care unit (CCU) admission, antibiotic prescribing and microbiology results within 10 days of COVID-19 diagnosis were analysed. Results: 1155 patients were identified. 32.9% (380) died. 12.4% (143) had positive microbiology. After excluding likely contaminants, 6.9% (80) had clinically significant microbiology. The most common organisms isolated from blood cultures were Escherichia coli 9.5% (7), Klebsiella pneumoniae 4.0% (3), and Staphylococcus aureus 2.7% (2). A high percentage of blood cultures yielded coagulase negative staphylococci (51/74, 68.9%) and likely represented contamination. Organisms isolated from lower respiratory tract samples included Candida albicans 44.4% (12), Staphylococcus aureus 22.2% (6), Klebsiella species 11.0% (3), Pseudomonas aeruginosa 11.0% (3), and Citrobacter species 11% (3). Legionella and pneumococcal urinary antigen tests were positive in 0/117 and 2/71 (2.8%) samples. 91% (1051) of patients received antibiotics. Clarithromycin (24.2% total antibiotic use) and amoxicillin (21%) were most frequently used, followed by piperacillin-tazobactam (12.6%), gentamicin (10.6%), co-amoxiclav (9.3%) and meropenem (3.2%). Piperacillin-tazobactam or meropenem use was associated with a higher length of stay and mortality. Conclusions: Positive microbiology in COVID-19 patients is uncommon. Antibiotic use was widespread, despite lack of microbiological evidence of co-infection. When present, positive microbiology was more likely due to gram negative bacteria. Current local clinical and antimicrobial guidelines have incorporated these findings and recommend against routine antibiotic use in COVID-19 patients

Cardiovascular disease biomarkers are associated with declining renal function in type 2 diabetes

Aims/hypothesis: We investigated whether biochemical cardiovascular risk factors and/or markers of subclinical cardiovascular disease were associated with the development of reduced renal function in people with type 2 diabetes. Methods: A cohort of 1066 Scottish men and women aged 60–74 years with type 2 diabetes from the Edinburgh Type 2 Diabetes Study were followed up for a median of 6.7 years. New-onset reduced renal function was defined as two eGFRs <60 ml−1 min−1 (1.73 m)−2 at least 3 months apart with a > 25% decline from baseline eGFR. Ankle brachial pressure index (ABI), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT) were measured at baseline. Pulse wave velocity (PWV) and carotid intima media thickness were measured 1 year into follow-up. Data were analysed using Cox proportional hazards models. Results: A total of 119 participants developed reduced renal function during follow-up. ABI, PWV, NT-proBNP and hsTnT were all associated with onset of decline in renal function following adjustment for age and sex. These associations were attenuated after adjustment for additional diabetes renal disease risk factors (systolic BP, baseline eGFR, albumin:creatinine ratio and smoking pack-years), with the exception of hsTnT which remained independently associated (HR 1.51 [95% CI 1.22, 1.87]). Inclusion of hsTnT in a predictive model improved the continuous net reclassification index by 0.165 (0.008, 0.286). Conclusions/interpretation: Our findings demonstrate an association between hsTnT, a marker of subclinical cardiac ischaemia, and subsequent renal function decline. Further research is required to establish the predictive value of hsTnT and response to intervention

The M, E, and N structural proteins of the severe acute respiratory syndrome coronavirus are required for efficient assembly, trafficking, and release of virus-like particles

Copyright @ 2008 American Society for Microbiology.The production of virus-like particles (VLPs) constitutes a relevant and safe model to study molecular determinants of virion egress. The minimal requirement for the assembly of VLPs for the coronavirus responsible for severe acute respiratory syndrome in humans (SARS-CoV) is still controversial. Recent studies have shown that SARS-CoV VLP formation depends on either M and E proteins or M and N proteins. Here we show that both E and N proteins must be coexpressed with M protein for the efficient production and release of VLPs by transfected Vero E6 cells. This suggests that the mechanism of SARS-CoV assembly differs from that of other studied coronaviruses, which only require M and E proteins for VLP formation. When coexpressed, the native envelope trimeric S glycoprotein is incorporated onto VLPs. Interestingly, when a fluorescent protein tag is added to the C-terminal end of N or S protein, but not M protein, the chimeric viral proteins can be assembled within VLPs and allow visualization of VLP production and trafficking in living cells by state-of-the-art imaging technologies. Fluorescent VLPs will be used further to investigate the role of cellular machineries during SARS-CoV egress.The University of Hong Kong and the French Ministry of Health