ESTABLISHING A PLATFORM FOR SPRAY DRYING INHALABLE VACCINES IN SOUTH AFRICA

Mycobacterium bovis BCG is the current vaccine for tuberculosis (TB). However, BCG as it is currently administered shows highly variable efficacy in protecting adults against TB. The natural route of infection of TB is via inhalation of bacilli-containing aerosols and it is postulated that immunization by the natural route of infection may lead to a greater immunity given the fact that the lungs are the primary target of infection. By eliciting both local and systemic immune responses, it is anticipated that an inhaled form of BCG will offer greater protection against pulmonary TB. Current commercial BCG vaccine preparations are filled as bacterial suspensions in vials, dried through lyophilization and stabilized through refrigeration with a one year shelf life. However, freeze-dried BCG does not exhibit a particle form conducive for delivery via the aerosol route and must be injected. Spray drying studies by Harvard University and Medicine in Need (MEND) scientists have demonstrated that BCG could be spray dried into a viable aerosol with up to 1 year of stability under refrigerated conditions, with the potential for room temperature stability. To support the further preclinical development of the BCG aerosol for application in the developing world, MEND established a state-of-the-art Biosafety level 3 spray drying facility with local expertise in South Africa, where the vaccine will be produced for an IND-enabling toxicology study meeting OECD Good Laboratory Practice (GLP) requirements. Frozen BCG bulk is spray dried and the resulting dry powder is characterized in terms of viability and aerosol properties. The dried BCG aerosol is then aseptically filled into capsules using a semi-automatic filling device for delivery using a low-cost hand-held inhaler. In conclusion, the spray drying technology was successfully transferred from Harvard University to the MEND facility in Pretoria. MEND is developing local expertise and infrastructure to support further preclinical and clinical development of BCG for inhalation

Gender and racial disparity for hospital emergency service usage in USA: a quantitative analysis for various age groups during 2010–2017.

Background: Annually emergency department (ED) services are utilized by more than 100 million Americans making ED usage trends important determinants of healthcare quality, outcomes and cost. Previous workers have demonstrated the existence of disparity in various healthcare services in USA although a comprehensive analysis has not been undertaken. Dahlgren and Whitehead rainbow model has offered insights for multiple factors of influence on an individual’s health and focuses on the relationships among these factors. The Commission on Social Determinants of Health (CSDH; WHO initiatives) suggests that the social and environmental factors are at the root of most of the inequalities responsible for both communicable and non-communicable diseases. Methods: The objectives of this study were to quantify the existing disparity in ED usage between 2010– 2017 by age, race and gender primarily using the Federal and State databases and comparing the quantitative trends with prior works from 2006–2020 that shed lights on health disparity. Single user normalization was developed to achieve randomization to reduce the heterogeneity of the database. Results: Each age group was represented by the usage pattern of the “single” average individual revealing significantly different ED usage for different age groups. Black and white Americans as well as males and females showed large variation indicative of racial and gender disparity. Conclusions: This is the first comprehensive meta-analysis demonstrating racial and gender specific variation in the usage of emergency health care services that exist in USA and seem to be multifactorial and age specific. Using a tool of single user normalization developed in this work as a means of randomization these disparities were quantified and may help identify such disparity trends in other regions that suffer from similar disparities

An evaluation of the current extent and potential spread of Black Bass invasions in South Africa

Black Bass, a collective name for members of the centrarchid genus Micropterus, are native to North America, but have been introduced globally to enhance recreational angling. This study assessed the distribution of Micropterus salmoides, M. dolomieu and M. punctulatus in South Africa using both formal (survey-based) and informal (tournament data and social media) information sources. Analysis of the distribution data showed habitat bias between the data sources. Survey data from formal information sources were dominated by locality records in riverine environments while those derived from informal information sources focused more on lacustrine habitats. Presence data were used to develop niche models to identify suitable areas for their establishment. The predicted distribution range of M. salmoides revealed a broad suitability over most of South Africa, however, the Cape Fold Ecoregion and all coastal regions were most suitable for the establishment for both M. dolomieu and M. punctulatus. Flow accumulation and precipitation of coldest quarter were the most important environmental variables associated with the presence of all Black Bass species in South Africa. In addition, anthropogenic disturbance such as agricultural activities were associated with the presence of both Smallmouth Bass and Spotted Bass. An extensive area-based invasion debt was observed for all Micropterus spp. The potential for further spread of Black Bass in South Africa is of ecological concern because of their impact on native biota

Profile: Agincourt health and socio-demographic surveillance system.

The Agincourt health and socio-demographic surveillance system (HDSS), located in rural northeast South Africa close to the Mozambique border, was established in 1992 to support district health systems development led by the post-apartheid ministry of health. The HDSS (90 000 people), based on an annual update of resident status and vital events, now supports multiple investigations into the causes and consequences of complex health, population and social transitions. Observational work includes cohorts focusing on different stages along the life course, evaluation of national policy at population, household and individual levels and examination of household responses to shocks and stresses and the resulting pathways influencing health and well-being. Trials target children and adolescents, including promoting psycho-social well-being, preventing HIV transmission and reducing metabolic disease risk. Efforts to enhance the research platform include using automated measurement techniques to estimate cause of death by verbal autopsy, full 'reconciliation' of in- and out-migrations, follow-up of migrants departing the study area, recording of extra-household social connections and linkage of individual HDSS records with those from sub-district clinics. Fostering effective collaborations (including INDEPTH multi-centre work in adult health and ageing and migration and urbanization), ensuring cross-site compatibility of common variables and optimizing public access to HDSS data are priorities

Diagnostic accuracy of a three-gene Mycobacterium tuberculosis host response cartridge using fingerstick blood for childhood tuberculosis: a multicentre prospective study in low-income and middle-income countries

BACKGROUND: Childhood tuberculosis remains a major cause of morbidity and mortality in part due to missed diagnosis. Diagnostic methods with enhanced sensitivity using easy-to-obtain specimens are needed. We aimed to assess the diagnostic accuracy of the Cepheid Mycobacterium tuberculosis Host Response prototype cartridge (MTB-HR), a candidate test measuring a three-gene transcriptomic signature from fingerstick blood, in children with presumptive tuberculosis disease. METHODS: RaPaed-TB was a prospective diagnostic accuracy study conducted at four sites in African countries (Malawi, Mozambique, South Africa, and Tanzania) and one site in India. Children younger than 15 years with presumptive pulmonary or extrapulmonary tuberculosis were enrolled between Jan 21, 2019, and June 30, 2021. MTB-HR was performed at baseline and at 1 month in all children and was repeated at 3 months and 6 months in children on tuberculosis treatment. Accuracy was compared with tuberculosis status based on standardised microbiological, radiological, and clinical data. FINDINGS: 5313 potentially eligible children were screened, of whom 975 were eligible. 784 children had MTB-HR test results, of whom 639 had a diagnostic classification and were included in the analysis. MTB-HR differentiated children with culture-confirmed tuberculosis from those with unlikely tuberculosis with a sensitivity of 59·8% (95% CI 50·8–68·4). Using any microbiological confirmation (culture, Xpert MTB/RIF Ultra, or both), sensitivity was 41·6% (34·7–48·7), and using a composite clinical reference standard, sensitivity was 29·6% (25·4–34·2). Specificity for all three reference standards was 90·3% (95% CI 85·5–94·0). Performance was similar in different age groups and by malnutrition status. Among children living with HIV, accuracy against the strict reference standard tended to be lower (sensitivity 50·0%, 15·7–84·3) compared with those without HIV (61·0%, 51·6–69·9), although the difference did not reach statistical significance. Combining baseline MTB-HR result with one Ultra result identified 71·2% of children with microbiologically confirmed tuberculosis. INTERPRETATION: MTB-HR showed promising diagnostic accuracy for culture-confirmed tuberculosis in this large, geographically diverse, paediatric cohort and hard-to-diagnose subgroups. FUNDING: European and Developing Countries Clinical Trials Partnership, UK Medical Research Council, Swedish International Development Cooperation Agency, Bundesministerium für Bildung und Forschung; German Center for Infection Research (DZIF)

Chitosan–Starch–Keratin composites: Improving thermo-mechanical and degradation properties through chemical modification

The lysozyme test shows an improved in the degradability rate, the weight loss of the films at 21 days is reduced from 73 % for chitosan-starch matrix up to 16 % for the composites with 5wt% of quill; but all films show a biodegradable character depending on keratin type and chemical modification. The outstanding properties related to the addition of treated keratin materials show that these natural composites are a remarkable alternative to potentiat-ing chitosan–starch films with sustainable featuresChitosan–starch polymers are reinforced with different keratin materials obtained from chicken feather. Keratin materials are treated with sodium hydroxide; the modified surfaces are rougher in comparison with untreated surfaces, observed by Scanning Electron Microscopy. The results obtained by Differential Scanning Calorimetry show an increase in the endothermic peak related to water evaporation of the films from 92 °C (matrix) up to 102–114 °C (reinforced composites). Glass transition temperature increases from 126 °C in the polymer matrix up to 170–200 °C for the composites. Additionally, the storage modulus in the composites is enhanced up to 1614 % for the composites with modified ground quill, 2522 % for composites with modified long fiber and 3206 % for the composites with modified short fiber. The lysozyme test shows an improved in the degradability rate, the weight loss of the films at 21 days is reduced from 73 % for chitosan-starch matrix up to 16 % for the composites with 5wt% of quill; but all films show a biodegradable character depending on keratin type and chemical modification. The outstanding properties related to the addition of treated keratin materials show that these natural composites are a remarkable alternative to potentiat-ing chitosan–starch films with sustainable featuresUniversidad Autónoma del Estado de México Tecnológico Nacional de México, Instituto Tecnológico de Querétaro Universidad Nacional Autónoma de México Tecnológico Nacional de México, Instituto Tecnológico de Celaya Universidad Autónoma de Cd. Juáre

Perspectives from the 2nd International Post-Tuberculosis Symposium: mobilising advocacy and research for improved outcomes

In 2020, it was estimated that there were 155 million survivors of TB alive, all at risk of possible post TB disability. The 2nd International Post-Tuberculosis Symposium (Stellenbosch, South Africa) was held to increase global awareness and empower TB-affected communities to play an active role in driving the agenda. We aimed to update knowledge on post-TB life and illness, identify research priorities, build research collaborations and highlight the need to embed lung health outcomes in clinical TB trials and programmatic TB care services. The symposium was a multidisciplinary meeting that included clinicians, researchers, TB survivors, funders and policy makers. Ten academic working groups set their own goals and covered the following thematic areas: 1) patient engagement and perspectives; 2) epidemiology and modelling; 3) pathogenesis of post-TB sequelae; 4) post-TB lung disease; 5) cardiovascular and pulmonary vascular complications; 6) neuromuscular & skeletal complications; 7) paediatric complications; 8) economic-social and psychological (ESP) consequences; 9) prevention, treatment and management; 10) advocacy, policy and stakeholder engagement. The working groups provided important updates for their respective fields, highlighted research priorities, and made progress towards the standardisation and alignment of post-TB outcomes and definitions

Reinterpretation of LHC Results for New Physics: Status and recommendations after Run 2

We report on the status of efforts to improve the reinterpretation of searches and measurements at the LHC in terms of models for new physics, in the context of the LHC Reinterpretation Forum. We detail current experimental offerings in direct searches for new particles, measurements, technical implementations and Open Data, and provide a set of recommendations for further improving the presentation of LHC results in order to better enable reinterpretation in the future. We also provide a brief description of existing software reinterpretation frameworks and recent global analyses of new physics that make use of the current data

Soil Moisture datasets (Hess-2018-546)

The datasets presented serves as supplementary material for the manuscript titled “Evaluation of soil moisture from CCAM-CABLE simulation, satellite-based models estimates and satellite observations: Skukuza and Malopeni flux towers region case study”, submitted to the journal of hydrology and earth system sciences (https://doi.org/10.5194/hess-2018-546). The following datasets are provided to reproduce the graphics on the manuscript and the detailed descriptions of the various datasets are provided in the manuscript. The scripts for reproducing the plots may be found at https://rpubs.com/FKhosa/hess-2018-546. The datasets are grouped in different folders for different sections of the manuscript. 1. Datasets describing the study region (Section 2) are contained in the folder “Study-region” • Koeppen climate types (“Koeppen-Geiger.csv”): this dataset is sourced from http://koeppen-geiger.vu-wien.ac.at/present.htm and is used to represent the climate types for the study region (Figure 2a). • Elevation/Topographic data (“Topography-25km.tif”): this dataset is sourced from https://www.ngdc.noaa.gov/mgg/fliers/06mgg01.html and is used to represent the topography for the study region (Figure 2b). • Soil type’s data (“soil-types.csv”): this dataset is sourced from https://soilgrids.org and is used to represent the soil types for the study region (Figure 2c). 2. Various soil moisture datasets discussed and analyse in Section 3 namely; • In situ observations: datasets for the two evaluation sites (i.e., Skukuza and Malopeni) may be requested from [email protected], parts of the dataset for Skukuza can be accessed from FLUXNET. • CCAM-CABLE: this dataset is available on request from [email protected]. Aggregated data is partly provided in the “MI” folder. • ESA: this dataset is available on request from the custodians of the data (www.esa-soilmoisture-cci.org/). • GLEAM: this dataset is available on request from the custodians of the data (www.gleam.eu). 3. Plotting data for Figure 3 is contained in the folder “Seasonal plots”, data sets for producing Figure 4a and 4b are contained in the folder “Taylor & NMB”. Datasets for plotting Figure 6 is contained in the folder “Boxplots”. Mutual information is calculated using data in the folder “MI” subfolder “data-for-computation” resulting datasets for plotting are contained in the subfolder “data-for-plotting”