Transpiration-Cooled Spacecraft-Insulation-Repair Fasteners

Transpiration-cooled fasteners are proposed that operate like an open-loop heat pipe (self-tapping screws, bolts, and spikes) for use in on-orbit repair of thermal- insulation of a space shuttle or other spacecraft. By limiting the temperature rise of such a fastener and of the adjacent repair material and thermal protection system, the transpiration cooling would contribute to the ability of the repair to retain its strength and integrity in the high-heat-flux, oxidizing environment of reentry into the atmosphere of the Earth. A typical fastener according to the proposal would include a hollow refractory-metal, refractory-composite, or ceramic screw or bolt, the central cavity of which would be occupied by a porous refractory- metal or ceramic plug that would act as both a reservoir and a wick for a transpirant liquid. The plug dimensions, the plug material, and the sizes of the pores would be chosen in conjunction with the transpirant liquid so that (1) capillary pumping could be relied upon to transport the liquid to the heated surface, where the liquid would be vaporized, and (2) the amount of liquid would suffice for protecting against the anticipated heat flux and integrated heat load

High-Sensitivity Cardiac Troponin and New-Onset Heart Failure: A Systematic Review and Meta-Analysis of 67,063 Patients With 4,165 Incident Heart Failure Events.

OBJECTIVES: The aim of this study was to systematically collate and appraise the available evidence regarding the association between high-sensitivity cardiac troponin (hs-cTn) and incident heart failure (HF) and the added value of hs-cTn in HF prediction. BACKGROUND: Identification of subjects at high risk for HF and early risk factor modification with medications such as angiotensin-converting enzyme inhibitors may delay the onset of HF. Hs-cTn has been suggested as a prognostic marker for the incidence of first-ever HF in asymptomatic subjects. METHODS: PubMed, Embase, and Web of Science were systematically searched for prospective cohort studies published before January 2017 that reported associations between hs-cTn and incident HF in subjects without baseline HF. Study-specific multivariate-adjusted hazard ratios (HRs) were pooled using random-effects meta-analysis. RESULTS: Data were collated from 16 studies with a total of 67,063 subjects and 4,165 incident HF events. The average age was 57 years, and 47% were women. Study quality was high (Newcastle-Ottawa score 8.2 of 9). In a comparison of participants in the top third with those in the bottom third of baseline values of hs-cTn, the pooled multivariate-adjusted HR for incident HF was 2.09 (95% confidence interval [CI]: 1.76 to 2.48; p < 0.001). Between-study heterogeneity was high, with an I2 value of 80%. HRs were similar in men and women (2.29 [95% CI: 1.64 to 3.21] vs. 2.18 [95% CI: 1.68 to 2.81]) and for hs-cTnI and hs-cTnT (2.09 [95% CI: 1.53 to 2.85] vs. 2.11 [95% CI: 1.69 to 2.63]) and across other study-level characteristics. Further adjustment for B-type natriuretic peptide yielded a similar HR of 2.08 (95% CI: 1.64 to 2.65). Assay of hs-cTn in addition to conventional risk factors provided improvements in the C index of 1% to 3%. CONCLUSIONS: Available prospective studies indicate a strong association of hs-cTn with the risk of first-ever HF and significant improvements in HF prediction

Socioeconomic Deprivation and Survival After Heart Transplantation in England: An Analysis of the United Kingdom Transplant Registry.

BACKGROUND: Socioeconomic deprivation (SED) is associated with shorter survival across a range of cardiovascular and noncardiovascular diseases. The association of SED with survival after heart transplantation in England, where there is universal healthcare provision, is unknown. METHODS AND RESULTS: Long-term follow-up data were obtained for all patients in England who underwent heart transplantation between 1995 and 2014. We used the United Kingdom Index of Multiple Deprivation (UK IMD), a neighborhood level measure of SED, to estimate the relative degree of deprivation for each recipient. Cox proportional hazard models were used to examine the association between SED and overall survival and conditional survival (dependant on survival at 1 year after transplantation) during follow-up. Models were stratified by transplant center and adjusted for donor and recipient age and sex, ethnicity, serum creatinine, diabetes mellitus, and heart failure cause. A total of 2384 patients underwent heart transplantation. There were 1101 deaths during 17 040 patient-year follow-up. Median overall survival was 12.6 years, and conditional survival was 15.6 years. Comparing the most deprived with the least deprived quintile, adjusted hazard ratios for all-cause mortality were 1.27 (1.04-1.55; P=0.021) and 1.59 (1.22-2.09; P=0.001) in the overall and conditional models, respectively. Median overall survival and conditional survival were 3.4 years shorter in the most deprived quintile than in the least deprived. CONCLUSIONS: Higher SED is associated with shorter survival in heart transplant recipients in England and should be considered when comparing outcomes between centers. Future research should seek to identify modifiable mediators of this association.No direct funding was provided for the conduct of this study. JE completed part of this work as part of an academic clinical fellowship, where he spent time at the University of Cambridge, Cardiovascular Epidemiology Unit receiving training on research methods, supported by SK and EDA. The Cardiovascular Epidemiology Unit is funded by the UK Medical Research Council (G0800270), British Heart Foundation (SP/09/002), British Heart Foundation Cambridge Cardiovascular Centre of Excellence, and UK National Institute for Health Research Cambridge Biomedical Research Centre.This is the author accepted manuscript. The final version is available from American Heart Association via https://doi.org/10.1161/CIRCOUTCOMES.116.00265

Emergence: Key physical issues for deeper philosophical inquiries

A sketch of three senses of emergence and a suggestive view on the emergence of time and the direction of time is presented. After trying to identify which issues philosophers interested in emergent phenomena in physics view as important I make several observations pertaining to the concepts, methodology and mechanisms required to understand emergence and describe a platform for its investigation. I then identify some key physical issues which I feel need be better appreciated by the philosophers in this pursuit. I end with some comments on one of these issues, that of coarse-graining and persistent structures.Comment: 16 pages. Invited Talk at the Heinz von Foerster Centenary International Conference on Self-Organization and Emergence: Emergent Quantum Mechanics (EmerQuM11). Nov. 10-13, 2011, Vienna, Austria. Proceedings to appear in J. Phys. (Conf. Series

Emergence: Key physical issues for deeper philosophical inquiries

A sketch of three senses of emergence and a suggestive view on the emergence of time and the direction of time is presented. After trying to identify which issues philosophers interested in emergent phenomena in physics view as important I make several observations pertaining to the concepts, methodology and mechanisms required to understand emergence and describe a platform for its investigation. I then identify some key physical issues which I feel need be better appreciated by the philosophers in this pursuit. I end with some comments on one of these issues, that of coarse-graining and persistent structures.Comment: 16 pages. Invited Talk at the Heinz von Foerster Centenary International Conference on Self-Organization and Emergence: Emergent Quantum Mechanics (EmerQuM11). Nov. 10-13, 2011, Vienna, Austria. Proceedings to appear in J. Phys. (Conf. Series

Prognostic value of three iron deficiency definitions in patients with advanced heart failure

Aims: There is uncertainty about the definition of iron deficiency (ID) and the association between ID and prognosis in patients with advanced heart failure. We evaluated three definitions of ID in patients referred for heart transplantation. Methods and results: Consecutive patients assessed for heart transplantation at a single UK centre between January 2010 and May 2022 were included. ID was defined as (1) serum ferritin concentration of <100 ng/ml, or 100–299 ng/ml with transferrin saturation <20% (guideline definition), (2) serum iron concentration ≤13 μmol/L, or (3) transferrin saturation <20%. The primary outcome measure was a composite of all-cause mortality, urgent heart transplantation or need for mechanical circulatory support. Overall, 801 patients were included, and the prevalence of ID was 39–55% depending on the definition used. ID, defined by either serum iron or transferrin saturation, was an independent predictor of the primary outcome measure (hazard ratio [HR] 1.532, 95% confidence interval [CI] 1.264–1.944, and HR 1.595, 95% CI 1.323–2.033, respectively), but the same association was not seen with the guideline definition of ID (HR 1.085, 95% CI 0.8827–1.333). These findings were robust in multivariable Cox regression analysis. ID, by all definitions, was associated with lower 6-min walk distance, lower peak oxygen consumption, higher intra-cardiac filling pressures and lower cardiac output. Conclusions: Iron deficiency, when defined by serum iron concentration or transferrin saturation, was associated with increased frequency of adverse clinical outcomes in patients with advanced heart failure. The same association was not seen with guideline definition of ID

Microbiological, histological, immunological, and toxin response to antibiotic treatment in the mouse model of Mycobacterium ulcerans disease.

Mycobacterium ulcerans infection causes a neglected tropical disease known as Buruli ulcer that is now found in poor rural areas of West Africa in numbers that sometimes exceed those reported for another significant mycobacterial disease, leprosy, caused by M. leprae. Unique among mycobacterial diseases, M. ulcerans produces a plasmid-encoded toxin called mycolactone (ML), which is the principal virulence factor and destroys fat cells in subcutaneous tissue. Disease is typically first manifested by the appearance of a nodule that eventually ulcerates and the lesions may continue to spread over limbs or occasionally the trunk. The current standard treatment is 8 weeks of daily rifampin and injections of streptomycin (RS). The treatment kills bacilli and wounds gradually heal. Whether RS treatment actually stops mycolactone production before killing bacilli has been suggested by histopathological analyses of patient lesions. Using a mouse footpad model of M. ulcerans infection where the time of infection and development of lesions can be followed in a controlled manner before and after antibiotic treatment, we have evaluated the progress of infection by assessing bacterial numbers, mycolactone production, the immune response, and lesion histopathology at regular intervals after infection and after antibiotic therapy. We found that RS treatment rapidly reduced gross lesions, bacterial numbers, and ML production as assessed by cytotoxicity assays and mass spectrometric analysis. Histopathological analysis revealed that RS treatment maintained the association of the bacilli with (or within) host cells where they were destroyed whereas lack of treatment resulted in extracellular infection, destruction of host cells, and ultimately lesion ulceration. We propose that RS treatment promotes healing in the host by blocking mycolactone production, which favors the survival of host cells, and by killing M. ulcerans bacilli