Study made to establish parameters and limitations of explosive welding

It is theorized that metal jetting must be present for welding to occur, therefore an explosive weld interface may indicate the relation between the metal jet velocity and shock wave velocity in welding. Parameters for effecting explosive welding in patches of 3 or 4 inches in diameter were established, and found applicable to explosive welding of patches of various sizes

Conceptual design study for a teleoperator visual system, phase 2

An analysis of the concept for the hybrid stereo-monoscopic television visual system is reported. The visual concept is described along with the following subsystems: illumination, deployment/articulation, telecommunications, visual displays, and the controls and display station

Application of advanced technology to space automation

Automated operations in space provide the key to optimized mission design and data acquisition at minimum cost for the future. The results of this study strongly accentuate this statement and should provide further incentive for immediate development of specific automtion technology as defined herein. Essential automation technology requirements were identified for future programs. The study was undertaken to address the future role of automation in the space program, the potential benefits to be derived, and the technology efforts that should be directed toward obtaining these benefits

Nitric Oxide Contributes to Vasomotor Tone in Hypertensive African Americans Treated With Nebivolol and Metoprolol

Endothelial dysfunction is more prevalent in African Americans (AAs) compared with whites. The authors hypothesized that nebivolol, a selective β1 -antagonist that stimulates nitric oxide (NO), will improve endothelial function in AAs with hypertension when compared with metoprolol. In a double-blind, randomized, crossover study, 19 AA hypertensive patients were randomized to a 12-week treatment period with either nebivolol 10 mg or metoprolol succinate 100 mg daily. Forearm blood flow (FBF) was measured using plethysmography at rest and after intra-arterial infusion of acetylcholine and sodium nitroprusside to estimate endothelium-dependent and independent vasodilation, respectively. Physiologic vasodilation was assessed during hand-grip exercise. Measurements were repeated after NO blockade with L-N(G) -monomethylarginine (L-NMMA) and after inhibition of endothelium-derived hyperpolarizing factor (EDHF) with tetraethylammonium chloride (TEA). NO blockade with L-NMMA produced a trend toward greater vasoconstriction during nebivolol compared with metoprolol treatment (21% vs 12% reduction in FBF, P=.06, respectively). This difference was more significant after combined administration of L-NMMA and TEA (P\u3c.001). Similarly, there was a contribution of NO to exercise-induced vasodilation during nebivolol but not during metoprolol treatment. There were significantly greater contributions of NO and EDHF to resting vasodilator tone and of NO to exercise-induced vasodilation with nebivolol compared with metoprolol in AAs with hypertension

Efficacy of RTS,S malaria vaccines: individual-participant pooled analysis of phase 2 data.

BACKGROUND: The efficacy of RTS,S/AS01 as a vaccine for malaria is being tested in a phase 3 clinical trial. Early results show significant, albeit partial, protection against clinical malaria and severe malaria. To ascertain variations in vaccine efficacy according to covariates such as transmission intensity, choice of adjuvant, age at vaccination, and bednet use, we did an individual-participant pooled analysis of phase 2 clinical data. METHODS: We analysed data from 11 different sites in Africa, including 4453 participants. We measured heterogeneity in vaccine efficacy by estimating the interactions between covariates and vaccination in pooled multivariable Cox regression and Poisson regression analyses. Endpoints for measurement of vaccine efficacy were infection, clinical malaria, severe malaria, and death. We defined transmission intensity levels according to the estimated local parasite prevalence in children aged 2-10 years (PrP₂₋₁₀), ranging from 5% to 80%. Choice of adjuvant was either AS01 or AS02. FINDINGS: Vaccine efficacy against all episodes of clinical malaria varied by transmission intensity (p=0·001). At low transmission (PrP₂₋₁₀ 10%) vaccine efficacy was 60% (95% CI 54 to 67), at moderate transmission (PrP₂₋₁₀ 20%) it was 41% (21 to 57), and at high transmission (PrP₂₋₁₀ 70%) the efficacy was 4% (-10 to 22). Vaccine efficacy also varied by adjuvant choice (p<0·0001)--eg, at low transmission (PrP₂₋₁₀ 10%), efficacy varied from 60% (95% CI 54 to 67) for AS01 to 47% (14 to 75) for AS02. Variations in efficacy by age at vaccination were of borderline significance (p=0·038), and bednet use and sex were not significant covariates. Vaccine efficacy (pooled across adjuvant choice and transmission intensity) varied significantly (p<0·0001) according to time since vaccination, from 36% efficacy (95% CI 24 to 45) at time of vaccination to 0% (-38 to 38) after 3 years. INTERPRETATION: Vaccine efficacy against clinical disease was of limited duration and was not detectable 3 years after vaccination. Furthermore, efficacy fell with increasing transmission intensity. Outcomes after vaccination cannot be gauged accurately on the basis of one pooled efficacy figure. However, predictions of public-health outcomes of vaccination will need to take account of variations in efficacy by transmission intensity and by time since vaccination. FUNDING: Medical Research Council (UK); Bill & Melinda Gates Foundation Vaccine Modelling Initiative; Wellcome Trust

Matrix Black Holes

Four and five dimensional extremal black holes with nonzero entropy have simple presentations in M-theory as gravitational waves bound to configurations of intersecting M-branes. We discuss realizations of these objects in matrix models of M-theory, investigate the properties of zero-brane probes, and propose a measure of their internal density. A scenario for black hole dynamics is presented.Comment: 26 pages, harvmac; a few more references and additional comment

Barriers to and Facilitators of Engagement With mHealth Technology for Remote Measurement and Management of Depression: Qualitative Analysis

BACKGROUND: Mobile technology has the potential to provide accurate, impactful data on the symptoms of depression, which could improve health management or assist in early detection of relapse. However, for this potential to be achieved, it is essential that patients engage with the technology. Although many barriers to and facilitators of the use of this technology are common across therapeutic areas and technology types, many may be specific to cultural and health contexts. OBJECTIVE: This study aimed to determine the potential barriers to and facilitators of engagement with mobile health (mHealth) technology for remote measurement and management of depression across three Western European countries. METHODS: Participants (N=25; 4:1 ratio of women to men; age range, 25-73 years) who experienced depression participated in five focus groups held in three countries (two in the United Kingdom, two in Spain, and one in Italy). The focus groups investigated the potential barriers to and facilitators of the use of mHealth technology. A systematic thematic analysis was used to extract themes and subthemes. RESULTS: Facilitators and barriers were categorized as health-related factors, user-related factors, and technology-related factors. A total of 58 subthemes of specific barriers and facilitators or moderators emerged. A core group of themes including motivation, potential impact on mood and anxiety, aspects of inconvenience, and ease of use was noted across all countries. CONCLUSIONS: Similarities in the barriers to and facilitators of the use of mHealth technology have been observed across Spain, Italy, and the United Kingdom. These themes provide guidance on ways to promote the design of feasible and acceptable cross-cultural mHealth tools. ©Sara Simblett, Faith Matcham, Sara Siddi, Viola Bulgari, Chiara Barattieri di San Pietro, Jorge Hortas López, José Ferrão, Ashley Polhemus, Josep Maria Haro, Giovanni de Girolamo, Peter Gamble, Hans Eriksson, Matthew Hotopf, Til Wykes, RADAR-CNS Consortium. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 30.01.2019

Impact of RTS,S/AS02A and RTS,S/AS01B on Genotypes of P. falciparum in Adults Participating in a Malaria Vaccine Clinical Trial

Objective:RTS,S, a candidate vaccine for malaria, is a recombinant protein expressed in yeast containing part of the circumsporozoite protein (CSP) sequence of 3D7 strain of Plasmodium falciparum linked to the hepatitis B surface antigen in a hybrid protein. The RTS,S antigen is formulated with GSK Biologicals\u27 proprietary Adjuvant Systems AS02A or AS01B. A recent trial of the RTS,S/AS02A and RTS,S/AS01B vaccines evaluated safety, immunogenicity and impact on the development of parasitemia of the two formulations. Parasite isolates from this study were used to determine the molecular impact of RTS,S/AS02A and RTS,S/AS01B on the multiplicity of infection (MOI) and the csp allelic characteristics of subsequent parasitemias.Design:The distribution of csp sequences and the MOI of the infecting strains were examined at baseline and in break-through infections from vaccinated individuals and from those receiving a non-malarial vaccine.Setting:The study was conducted in Kombewa District, western Kenya.Participants:Semi-immune adults from the three study arms provided isolates at baseline and during break-through infections.Outcome:Parasite isolates used for determining MOI and divergence of csp T cell&ndash;epitopes were 191 at baseline and 87 from break-through infections.Results:Grouping recipients of RTS,S/AS01A and RTS,S/AS02B together, vaccine recipients identified as parasite-positive by microscopy contained significantly fewer parasite genotypes than recipients of the rabies vaccine comparator (median in pooled RTS,S groups: 3 versus 4 in controls, P = 0.0313). When analyzed separately, parasitaemic individuals in the RTS,S/AS01B group, but not the RTS,S/AS02A group, were found to have significantly fewer genotypes than the comparator group. Two individual amino acids found in the vaccine construct (Q339 in Th2R and D371 in Th3R) were observed to differ in incidence between vaccine and comparator groups but in different directions; parasites harboring Q339 were less common among pooled RTS,S/AS vaccine recipients than among recipients of rabies vaccine, whereas parasites with D371 were more common among the RTS,S/AS groups.Conclusions:It is concluded that both RTS,S/AS vaccines reduce multiplicity of infection. Our results do not support the hypothesis that RTS,S/AS vaccines elicit preferential effects against pfcsp alleles with sequence similarity to the 3D7 pfcsp sequence employed in the vaccine construct

Listening to the patients’ voice: a conceptual framework of the walking experience

Background walking is crucial for an active and healthy ageing, but the perspectives of individuals living with walking impairment are still poorly understood. Objectives to identify and synthesise evidence describing walking as experienced by adults living with mobility-impairing health conditions and to propose an empirical conceptual framework of walking experience. Methods we performed a systematic review and meta-ethnography of qualitative evidence, searching seven electronic databases for records that explored personal experiences of walking in individuals living with conditions of diverse aetiology. Conditions included Parkinson’s disease, multiple sclerosis, chronic obstructive pulmonary disease, hip fracture, heart failure, frailty and sarcopenia. Data were extracted, critically appraised using the NICE quality checklist and synthesised using standardised best practices. Results from 2,552 unique records, 117 were eligible. Walking experience was similar across conditions and described by seven themes: (i) becoming aware of the personal walking experience, (ii) the walking experience as a link between individuals’ activities and sense of self, (iii) the physical walking experience, (iv) the mental and emotional walking experience, (v) the social walking experience, (vi) the context of the walking experience and (vii) behavioural and attitudinal adaptations resulting from the walking experience. We propose a novel conceptual framework that visually represents the walking experience, informed by the interplay between these themes. Conclusion a multi-faceted and dynamic experience of walking was common across health conditions. Our conceptual framework of the walking experience provides a novel theoretical structure for patient-centred clinical practice, research and public health

Walking on common ground: a cross-disciplinary scoping review on the clinical utility of digital mobility outcomes

Physical mobility is essential to health, and patients often rate it as a high-priority clinical outcome. Digital mobility outcomes (DMOs), such as real-world gait speed or step count, show promise as clinical measures in many medical conditions. However, current research is nascent and fragmented by discipline. This scoping review maps existing evidence on the clinical utility of DMOs, identifying commonalities across traditional disciplinary divides. In November 2019, 11 databases were searched for records investigating the validity and responsiveness of 34 DMOs in four diverse medical conditions (Parkinson’s disease, multiple sclerosis, chronic obstructive pulmonary disease, hip fracture). Searches yielded 19,672 unique records. After screening, 855 records representing 775 studies were included and charted in systematic maps. Studies frequently investigated gait speed (70.4% of studies), step length (30.7%), cadence (21.4%), and daily step count (20.7%). They studied differences between healthy and pathological gait (36.4%), associations between DMOs and clinical measures (48.8%) or outcomes (4.3%), and responsiveness to interventions (26.8%). Gait speed, step length, cadence, step time and step count exhibited consistent evidence of validity and responsiveness in multiple conditions, although the evidence was inconsistent or lacking for other DMOs. If DMOs are to be adopted as mainstream tools, further work is needed to establish their predictive validity, responsiveness, and ecological validity. Cross-disciplinary efforts to align methodology and validate DMOs may facilitate their adoption into clinical practice