An analysis of pre-clinical efficacy testing of antivenoms for sub-Saharan Africa: Inadequate independent scrutiny and poor-quality reporting are barriers to improving snakebite treatment and management

Background The World Health Organization’s strategy to halve snakebite mortality and morbidity by 2030 includes an emphasis on a risk-benefit process assessing the preclinical efficacy of antivenoms manufactured for sub-Saharan Africa. To assist this process, we systematically collected, standardised and analysed all publicly available data on the preclinical efficacy of antivenoms designed for sub-Saharan Africa. Methodology/Principal findings Using a systematic search of publication databases, we focused on publicly available preclinical reports of the efficacy of 16 antivenom products available in sub Saharan Africa. Publications since 1999 reporting the industry standard intravenous pre-incubation method of murine in vivo neutralisation of venom lethality (median effective dose [ED50]) were included. Eighteen publications met the criteria. To permit comparison of the several different reported ED50 values, it was necessary to standardise these to microlitre of antivenom resulting in 50% survival of mice challenged per milligram of venom (μl/mg). We were unable to identify publicly available preclinical data on four antivenoms, whilst data for six polyspecific antivenoms were restricted to a small number of venoms. Only four antivenoms were tested against a wide range of venoms. Examination of these studies for the reporting of key metrics required for interpreting antivenom ED50s were highly variable, as evidenced by eight different units being used for the described ED50 values. Conclusions/Significance There is a disturbing lack of (i) preclinical efficacy testing of antivenom for sub Saharan Africa, (ii) publicly available reports and (iii) independent scrutiny of this medically important data. Where reports do exist, the methods and metrics used are highly variable. This prevents comprehensive meta-analysis of antivenom preclinical efficacy, and severely reduces the utility of antivenom ED50 results in the decision making of physicians treating patients and of national and international health agencies. Here, we propose the use of a standardised result reporting checklist to resolve this issue. Implementation of these straightforward steps will deliver uniform evaluation of products across laboratories, facilitate meta-analyses, and contribute vital information for designing the clinical trials needed to achieve the WHO target of halving snakebite morbidity and mortality by 2030

An Atlas of Spectrophotometric Landolt Standard Stars

We present CCD observations of 102 Landolt standard stars obtained with the R-C spectrograph on the CTIO 1.5 m telescope. Using stellar atmosphere models we have extended the flux points to our six spectrophotometric secondary standards, in both the blue and the red, allowing us to produce flux-calibrated spectra that span a wavelength range from 3050 \AA to 1.1 \micron. Mean differences between UBVRI spectrophotometry computed using Bessell's standard passbands and Landolt's published photometry is found to be 1% or less. Observers in both hemispheres will find these spectra useful for flux-calibrating spectra and through the use of accurately constructed instrumental passbands be able to compute accurate corrections to bring instrumental magnitudes to any desired standard photometric system (S-corrections). In addition, by combining empirical and modeled spectra of the Sun, Sirius and Vega, we calculate and compare synthetic photometry to observed photometry taken from the literature for these three stars.Comment: Added referee's comments, minor corrections, replaced Table 1

MammoSapiens: eResearch of the lactation program.

Delivering bioinformatics power to life science researchers inevitably runs into problems of limited computing resources in the context of exponentially increasing data sources, access time, costs, lack of skills and, rapidly evolving technology and software tools with poorly defined standards. In this context the development of e-facilities to best enable collaborative research often needs to be customized to specific project applications in close cooperation with the experimentalist users and, to be concerned with the storage and management of results to allow more consistency and traceability of e-results on a broad access data mining platform. Here we showcase an internet based eResearch platform using the PHP/MySQL paradigm for the collaborative, integrative and comparative analysis of lactation related gene sequences and gene expression experiments to support lactation research. We also illustrate how these resources are used, how they enable research by allowing meta-analysis of data and results and, how the bottom-up development of customized eResearch components can lead to the production of more generic functional software tools and eResearch environments for deployment to a larger number of biological research users working on other bio-systems.<br /

MammoSapiens: eResearch of the lactation program. Building online facilities for collaborative molecular and evolutionary analysis of lactation and other biological systems from gene sequences and gene expression data.

Delivering bioinformatics power to life science researchers inevitably runs into problems of limited computing resources in the context of exponentially increasing data sources, access time, costs, lack of skills and, rapidly evolving technology and software tools with poorly defined standards. In this context the development of online facilities to best enable collaborative research often needs to be customized to specific project applications in close cooperation with the experimentalist users and, to be concerned with the storage and management of results to allow more consistency and traceability of results on a broad access data mining platform. Here we showcase an Internet based research platform using the PHP/MySQL paradigm for the collaborative, integrative and comparative analysis of lactation related gene sequences and gene expression experiments to support lactation research. We also illustrate how these resources are used, how they enable research by allowing meta-analysis of data and results and, how the bottom-up development of customized eResearch components can lead to the production of more generic functional software tools and eResearch environments for deployment to a larger number of biological researchers working on other bio-systems

Estimating Cost Functions for Resource Allocation Using Transmission Models: A Case Study of Tuberculosis Case Finding in South Africa.

OBJECTIVE: Cost functions linked to transmission dynamic models are commonly used to estimate the resources required for infectious disease policies. We present a conceptual and empirical approach for estimating these functions, allowing for nonconstant marginal costs. We aim to expand on the current approach which commonly assumes linearity of cost over scale. METHODS: We propose a theoretical framework adapted from the field of transport economics. We specify joint functions of production of services within a disease-specific program. We expand these functions to include qualitative insights of program expansion patterns. We present the difference in incremental total costs between an approach assuming constant unit costs and alternative approaches that assume economies of scale, scope and homogeneous or heterogeneous facility recruitment into the programme during scale-up. We illustrate the framework's application in tuberculosis, using secondary data from the literature and routine reporting systems in South Africa. RESULTS: Economies of capacity and scope substantially change cost estimates over time. Cost data requirements for the proposed approach included standardized and disaggregated unit costs (for a limited number of outputs) and information on the facilities network available to the program. CONCLUSIONS: The defined functional form will determine the magnitude and shape of costs when outputs and coverage are increasing. This in turn will impact resource allocation decisions. Infectious diseases modelers and economists should use transparent and empirically based cost models for analyses that inform resource allocation decisions. This framework describes a general approach for developing these models

Optical Photometry of the Type Ia SN 1999ee and the Type Ib/c SN 1999ex in IC 5179

We present UBVRIz lightcurves of the Type Ia SN 1999ee and the Type Ib/c SN 1999ex, both located in the galaxy IC 5179. SN 1999ee has an extremely well sampled lightcurve spanning from 10 days before Bmax through 53 days after peak. Near maximum we find systematic differences ~0.05 mag in photometry measured with two different telescopes, even though the photometry is reduced to the same local standards around the supernova using the specific color terms for each instrumental system. We use models for our bandpasses and spectrophotometry of SN 1999ee to derive magnitude corrections (S-corrections) and remedy this problem. This exercise demonstrates the need of accurately characterizing the instrumental system before great photometric accuracies of Type Ia supernovae can be claimed. It also shows that this effect can have important astrophysical consequences since a small systematic shift of 0.02 mag in the B-V color can introduce a 0.08 mag error in the extinction corrected peak B magnitudes of a supernova and thus lead to biased cosmological parameters. The data for the Type Ib/c SN 1999ex present us with the first ever observed shock breakout of a supernova of this class. These observations show that shock breakout occurred 18 days before Bmax and support the idea that Type Ib/c supernovae are due to core collapse of massive stars rather than thermonuclear disruption of white dwarfs.Comment: 55 pages, 15 figures, accepted by the Astronomical Journa