The effect of current Schistosoma mansoni infection on the immunogenicity of a candidate TB vaccine, MVA85A, in BCG-vaccinated adolescents: An open-label trial.

INTRODUCTION: Helminth infection may affect vaccine immunogenicity and efficacy. Adolescents, a target population for tuberculosis booster vaccines, often have a high helminth burden. We investigated effects of Schistosoma mansoni (Sm) on the immunogenicity and safety of MVA85A, a model candidate tuberculosis vaccine, in BCG-vaccinated Ugandan adolescents. METHODS: In this phase II open label trial we enrolled 36 healthy, previously BCG-vaccinated adolescents, 18 with no helminth infection detected, 18 with Sm only. The primary outcome was immunogenicity measured by Ag85A-specific interferon gamma ELISpot assay. Tuberculosis and schistosome-specific responses were also assessed by whole-blood stimulation and multiplex cytokine assay, and by antibody ELISAs. RESULTS: Ag85A-specific cellular responses increased significantly following immunisation but with no differences between the two groups. Sm infection was associated with higher pre-immunisation Ag85A-specific IgG4 but with no change in antibody levels following immunisation. There were no serious adverse events. Most reactogenicity events were of mild or moderate severity and resolved quickly. CONCLUSIONS: The significant Ag85A-specific T cell responses and lack of difference between Sm-infected and uninfected participants is encouraging for tuberculosis vaccine development. The implications of pre-existing Ag85A-specific IgG4 antibodies for protective immunity against tuberculosis among those infected with Sm are not known. MVA85A was safe in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT02178748

Embedded Sensors for Measuring Surface Regression

The development and evaluation of new hybrid and solid rocket motors requires accurate characterization of the propellant surface regression as a function of key operational parameters. These characteristics establish the propellant flow rate and are prime design drivers affecting the propulsion system geometry, size, and overall performance. There is a similar need for the development of advanced ablative materials, and the use of conventional ablatives exposed to new operational environments. The Miniature Surface Regression Sensor (MSRS) was developed to serve these applications. It is designed to be cast or embedded in the material of interest and regresses along with it. During this process, the resistance of the sensor is related to its instantaneous length, allowing the real-time thickness of the host material to be established. The time derivative of this data reveals the instantaneous surface regression rate. The MSRS could also be adapted to perform similar measurements for a variety of other host materials when it is desired to monitor thicknesses and/or regression rate for purposes of safety, operational control, or research. For example, the sensor could be used to monitor the thicknesses of brake linings or racecar tires and indicate when they need to be replaced. At the time of this reporting, over 200 of these sensors have been installed into a variety of host materials. An MSRS can be made in either of two configurations, denoted ladder and continuous (see Figure 1). A ladder MSRS includes two highly electrically conductive legs, across which narrow strips of electrically resistive material are placed at small increments of length. These strips resemble the rungs of a ladder and are electrically equivalent to many tiny resistors connected in parallel. A substrate material provides structural support for the legs and rungs. The instantaneous sensor resistance is read by an external signal conditioner via wires attached to the conductive legs on the non-eroding end of the sensor. The sensor signal can be transmitted from inside a high-pressure chamber to the ambient environment, using commercially available feedthrough connectors. Miniaturized internal recorders or wireless data transmission could also potentially be employed to eliminate the need for producing penetrations in the chamber case. The rungs are designed so that as each successive rung is eroded away, the resistance changes by an amount that yields a readily measurable signal larger than the background noise. (In addition, signal-conditioning techniques are used in processing the resistance readings to mitigate the effect of noise.) Hence, each discrete change of resistance serves to indicate the arrival of the regressing host material front at the known depth of the affected resistor rung. The average rate of regression between two adjacent resistors can be calculated simply as the distance between the resistors divided by the time interval between their resistance jumps. Advanced data reduction techniques have also been developed to establish the instantaneous surface position and regression rate when the regressing front is between rungs

Biochemical reference values in elderly black subjects

Biochemical reference values for the black age group of ≥ 65 years were determined from the black urban population of the Orange Free State. Biochemical investigations performed were those included in the Sequential Multiple Analyser Computer profile because it includes the 20 most requested clinical chemistry investigations. Most of the reference values corresponded to values for the same age groups in the Western world. There was no age-related rise in the alkaline phosphatase values, which suggested absence of occult Paget's disease. Reference values for serum total protein and globulin were found to be higher than values derived from elderly white groups

Evaluation of a disease specific rheumatoid arthritis self-management education program, a single group repeated measures study

Background: Rheumatoid Arthritis is a progressive and disabling disease, predicted to increase in prevalence over the next 50 years. Self-management is acknowledged as an integral part in the management of chronic disease. The rheumatoid arthritis specific self-management program delivered by health professionals was developed by Arthritis Western Australia in 2006. The purpose of this study was to determine whether this program would achieve early benefits in health related outcomes, and whether these improvements would be maintained for 12 months. Methods: Individuals with rheumatoid arthritis were referred from rheumatologists. Participants with co-existing inflammatory musculoskeletal conditions were excluded. All participants completed a 6-week program. Assessments occurred at baseline (8 weeks prior to intervention), pre-intervention, post-intervention, and 6 and 12 month follow ups. Outcomes measured included pain and fatigue (numerical rating scale, 0-10), depression and anxiety (hospital anxiety and depression questionnaire), health distress, and quality of life (SF-36 version 2). Results: There were significant improvements in mean [SD] fatigue (5.7 [2.4] to 5.1 [2.6]), depression (6.3 [4.3] to 5.6 [3.9]) and SF-36 mental health (44.5 [11.1] to 46.5 [9.5]) immediately following intervention, with long term benefits for depression (6.3 [4.3] to 4.9 [3.9]), and SF-36 subscales mental health (44.5 [11.1] to 47.8 [10.9]), role emotional (41.5 [13.2] to 46.5 [11.8]), role physical (35.0 [11.0] to 40.2 [12.1]) and physical function (34.8 [11.5] to 38.6 [10.7]). Conclusion: Participants in the program recorded significant improvements in depression and mental health post-intervention, which were maintained to 12 months follow up

The design of a JADE compliant manufacturing ontology and accompanying relational database schema

Published ArticleTo enable meaningful and consistent communication between different software systems in a particular domain (such as manufacturing, law or medicine), a standardised vocabulary and communication language is required by all the systems involved. Concepts in the domain about which the systems want to communicate are formalized in an ontology by establishing the meaning of concepts and creating relationships between them. The inputs to this process in found by analysing the physical domain and its processes. The resulting ontology structure is a computer useable representation of the physical domain about which the systems want to communicate. To enable the long term persistence of the actual data contained in these concepts and the enforcement of various business rules, a sufficiently powerful database system is required. This paper presents the design of a manufacturing ontology and its accompanying relational database schema that will be used in a manufacturing test domain

Analysis of two mutations in the MTHFR gene associated with mild hyperhomocysteinaemia – heterogeneous distribution in the South African population

Objective, The frequencies of mutations 677C→T and 1298A→C in the methylenetetrahydrofolate reductase (MTHFR) gene, previously shown to be associated with decreased enzyme activity that may lead to hyperhomocysteinaemia and consequently increased risk of cardiovascular disease (CVD), were determined in the South African population.Methods, Hinfi (677C→T) and MbolI (1298A→C) restriction enzyme analyses were performed on amplified DNA samples of 76 white, 73 coloured and 60 black subjects.Results, The mutant alleles of mutations 677C→T and 1298A..-+C were more common in the white (allele frequencies 0.36 and 0.37, respectively) than in the black population (0.04 and 0.09), while intermediate frequencies were detected in the coloured population (0,18 and 0.30); Homozygosity for mutation 677C → T was not detected in the black cohort, while this genotype was detected in 1 coloured (1.4%) and 8 white (105%) subjects, In the black population, 5% of the 60 subjects analysed were homozygous for mutation 1298A→C, compared with approximately 12% in both the white and coloured populations,Conclusions. Since hyperhomocysteinaemia is a risk factor for premature CVD, the heterogeneous distribution of the 677C→T and 1298A→C mutations across ethnic groups may partly explain ethnic differences in heart disease risk through decreased enzyme activity and hence increased homocysteine levels