The Regulatory Review Process in South Africa: Challenges and Opportunities for a New Improved System.

BACKGROUND: The aims of this study were to assess the regulatory review process in South Africa from 2015 to 2017, identify the key milestones and timelines; evaluate the effectiveness of measures to ensure consistency, transparency, timeliness, and predictability in the review process; and to provide recommendations for enhanced regulatory practices. METHODS: A questionnaire was completed by the Medicines Control Council (MCC) to describe the organization of the authority, record key milestones and timelines in the review process and to identify good review practices (GRevPs). RESULTS: Currently, the MCC conducts a full assessment of quality, efficacy, and safety data in the review of all applications. The overall regulatory median approval time decreased by 14% in 2017 (1411 calendar days) compared with that of 2016, despite the 27% increase in the number of applications. However, the MCC has no target for overall approval time of new active substance applications and no targets for key review milestones. Guidelines, standard operating procedures, and review templates are in place, while the formal implementation of GRevPs and the application of an electronic document management system are planned for the near future. CONCLUSIONS: As the MCC transitions to the newly established South Africa Health Products Regulatory Authority, it would be crucial for the authority to recognize the opportunities for an enhanced regulatory review and should consider models such as abridged assessment, which encompass elements of risk stratification and reliance. It is hoped that resource constraints may then be alleviated and capacity developed to meet target timelines.Peer reviewedFinal Published versio

Optimized Confinement of Fermions in Two Dimensions

One of the challenging features of studying model Hamiltonians with cold atoms in optical lattices is the presence of spatial inhomogeneities induced by the confining potential, which results in the coexistence of different phases. This paper presents Quantum Monte Carlo results comparing meth- ods for confining fermions in two dimensions, including conventional diagonal confinement (DC), a recently proposed 'off-diagonal confinement' (ODC), as well as a trap which produces uniform den- sity in the lattice. At constant entropy and for currently accessible temperatures, we show that the current DC method results in the strongest magnetic signature, primarily because of its judicious use of entropy sinks at the lattice edge. For d-wave pairing, we show that a constant density trap has the more robust signal and that ODC can implement a constant density profile. This feature is important to any prospective search for superconductivity in optical lattices

Analytical and developmental investigation of electron strip multipliers, phase 3 Final report

Operational gain fatigue mechanisms in continuous dynode electron multiplier

Analytical and developmental investigation of electron strip multipliers Final report

Operational characteristics of dynode electron strip multiplier

Isentropic Curves at Magnetic Phase Transitions

Experiments on cold atom systems in which a lattice potential is ramped up on a confined cloud have raised intriguing questions about how the temperature varies along isentropic curves, and how these curves intersect features in the phase diagram. In this paper, we study the isentropic curves of two models of magnetic phase transitions- the classical Blume-Capel Model (BCM) and the Fermi Hubbard Model (FHM). Both Mean Field Theory (MFT) and Monte Carlo (MC) methods are used. The isentropic curves of the BCM generally run parallel to the phase boundary in the Ising regime of low vacancy density, but intersect the phase boundary when the magnetic transition is mainly driven by a proliferation of vacancies. Adiabatic heating occurs in moving away from the phase boundary. The isentropes of the half-filled FHM have a relatively simple structure, running parallel to the temperature axis in the paramagnetic phase, and then curving upwards as the antiferromagnetic transition occurs. However, in the doped case, where two magnetic phase boundaries are crossed, the isentrope topology is considerably more complex

Vaginal Microbicides: Detecting Toxicities in Vivo that Paradoxically Increase Pathogen Transmission

BACKGROUND: Microbicides must protect against STD pathogens without causing unacceptable toxic effects. Microbicides based on nonoxynol-9 (N9) and other detergents disrupt sperm, HSV and HIV membranes, and these agents are effective contraceptives. But paradoxically N9 fails to protect women against HIV and other STD pathogens, most likely because it causes toxic effects that increase susceptibility. The mouse HSV-2 vaginal transmission model reported here: (a) Directly tests for toxic effects that increase susceptibility to HSV-2, (b) Determines in vivo whether a microbicide can protect against HSV-2 transmission without causing toxicities that increase susceptibility, and (c) Identifies those toxic effects that best correlate with the increased HSV susceptibility. METHODS: Susceptibility was evaluated in progestin-treated mice by delivering a low-dose viral inoculum (0.1 ID50) at various times after delivering the candidate microbicide to detect whether the candidate increased the fraction of mice infected. Ten agents were tested – five detergents: nonionic (N9), cationic (benzalkonium chloride, BZK), anionic (sodium dodecylsulfate, SDS), the pair of detergents in C31G (C14AO and C16B); one surface active agent (chlorhexidine); two non-detergents (BufferGel®, and sulfonated polystyrene, SPS); and HEC placebo gel (hydroxyethylcellulose). Toxic effects were evaluated by histology, uptake of a 'dead cell' dye, colposcopy, enumeration of vaginal macrophages, and measurement of inflammatory cytokines. RESULTS: A single dose of N9 protected against HSV-2 for a few minutes but then rapidly increased susceptibility, which reached maximum at 12 hours. When applied at the minimal concentration needed for brief partial protection, all five detergents caused a subsequent increase in susceptibility at 12 hours of ~20–30-fold. Surprisingly, colposcopy failed to detect visible sign of the N9 toxic effect that increased susceptibility at 12 hours. Toxic effects that occurred contemporaneously with increased susceptibility were rapid exfoliation and re-growth of epithelial cell layers, entry of macrophages into the vaginal lumen, and release of one or more inflammatory cytokines (Il-1β, KC, MIP 1α, RANTES). The non-detergent microbicides and HEC placebo caused no significant increase in susceptibility or toxic effects. CONCLUSION: This mouse HSV-2 model provides a sensitive method to detect microbicide-induced toxicities that increase susceptibility to infection. In this model, there was no concentration at which detergents provided protection without significantly increasing susceptibility.JHU Woodrow Wilson Fellowship; National Institutes of Health (Program Project A1 45967

Using monoclonal antibodies to prevent mucosal transmission of epidemic infectious diseases.

Passive immunization with antibodies has been shown to prevent a wide variety of diseases. Recent advances in monoclonal antibody technology are enabling the development of new methods for passive immunization of mucosal surfaces. Human monoclonal antibodies, produced rapidly, inexpensively, and in large quantities, may help prevent respiratory, diarrheal, and sexually transmitted diseases on a public health scale

Using publication metrics to highlight academic productivity and research impact

This article provides a broad overview of widely available measures of academic productivity and impact using publication data and highlights uses of these metrics for various purposes. Metrics based on publication data include measures such as number of publications, number of citations, the journal impact factor score, and the h-index, as well as emerging metrics based on document-level metrics. Publication metrics can be used for a variety of purposes for tenure and promotion, grant applications and renewal reports, benchmarking, recruiting efforts, and administrative purposes for departmental or university performance reports. The authors also highlight practical applications of measuring and reporting academic productivity and impact to emphasize and promote individual investigators, grant applications, or department output