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

Exploring the Dynamics and Impacts of Failed Teamwork in the Flight Deck: A Case Study Analysis of Contributing Factors and Mitigation Strategies

Crew Resource Management (CRM) is a crucial concept in aviation, emphasizing the coordinated use of all available resources, including human, equipment, and information, to ensure safe and efficient flight operations. CRM aims to enhance communication, decision-making, and situational awareness among flight crew members, thus reducing errors, mitigating risks, and improving overall operational efficiency. The CRM competencies include leadership, teamwork, and decision-making. The National Transportation Safety Board has determined poor teamwork was a contributing factor of major aircraft accidents. This ongoing project aims to investigate the teamwork competency within the operational hierarchies of Part 121 and Part 135 operations by examining accidents that occurred between the years 2000 and 2022. The study will delve into the dynamics of teamwork within regulatory frameworks and previous literature to identify patterns, challenges, and potential areas for improvement. By understanding the intricacies of teamwork within these operational structures, the goal is to enhance safety standards to help mitigate risks in the aviation industry

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

Modelling Animal Systems Paper: Update of the Dutch protein evaluation system for ruminants: the DVE/OEB2010 system

In the current Dutch protein evaluation system (the DVE/OEB1991 system), two characteristics are calculated for each feed: true protein digested in the intestine (DVE) and the rumen degradable protein balance (OEB). Of these, DVE represents the protein value of a feed, while OEB is the difference between the potential microbial protein synthesis (MPS) on the basis of available rumen degradable protein and that on the basis of available rumen degradable energy. DVE can be separated into three components: (i) feed crude protein undegraded in the rumen but digested in the small intestine, (ii) microbial true protein synthesized in the rumen and digested in the small intestine, and (iii) endogenous protein lost in the digestive processes. Based on new research findings, the DVE/OEB1991 system has recently been updated to the DVE/OEB2010 system. More detail and differentiation is included concerning the representation of chemical components in feed, the rumen degradation characteristics of these components, the efficiency of MPS and the fractional passage rates. For each chemical component, the soluble, washout, potentially degradable and truly non-degradable fractions are defined with separate fractional degradation rates. Similarly, fractional passage rates for each of these fractions were identified and partly expressed as a function of fractional degradation rate. Efficiency of MPS is related to the various fractions of the chemical components and their associated fractional passage rates. Only minor changes were made with respect to the amount of DVE required for maintenance and production purposes of the animal. Differences from other current protein evaluation systems, viz. the Cornell Net Carbohydrate and Protein system and the Feed into Milk system, are discussed

A comparison of in situ and in vitro methods to estimate in vivo fermentable organic matter of forages in ruminants

Farmers in five districts of north-eastern Uganda were interviewed to generate information on sweet potato production and constraints, with emphasis on damage by millipedes. Participatory rural appraisal methodology was used to interview 148 farmers. The peak period of planting sweet potato was from the end of May till the beginning of July in order to produce dried form food (amukeke) for storage in the dry season, which sets in around November. Vine cuttings were usually planted on mounds and weeding was mostly done only once. Osukut, Araka Red and Araka White were the most popular varieties. Many respondents obtained planting material from volunteer plants. Separation of plots over time and in space was often not practised. Sweet potato crop rotations were diverse. Millet, groundnut and maize were commonly grown after sweet potato. Cassava, sweet potato, groundnut and maize are host crops for millipedes and were often grown in succession. Millipede incidences were not statistically different for the three agro-ecological zones of north-eastern Uganda, but depended on the frequency of millipede hosts (including sweet potato) in the crop rotations. Groundnut planted after sweet potato had high levels of millipede attack. Millipede incidence was often associated with the incidence of weevils. The results of this inventory show that most farmers consider millipedes as a pest of sweet potato and other major food and cash crops, but that many farmers lack the knowledge to control them

Immune Amplification of Murine CD8+ Suppressor T Cells Induced via An Immune-Privileged Site: Quantifying Suppressor T Cells Functionally

BACKGROUND: CD8(+) suppressor T cells exert antigen-specific suppression of the expression of hypersensitivity by activated T cells. Therefore, CD8(+) suppressor T cells serve a major regulatory role for the control of active immunity. Accordingly, the number and/or activity of CD8(+) suppressor T cells should be influenced by an immune response to the antigen. To test this hypothesis we used an adoptive transfer assay that measures the suppression of the expression of delayed-type hypersensitivity (DTH) by CD8(+) suppressor T cells to quantify the antigen-specific suppression of DTH by these suppressor T cells. METHODS: Suppressor T cells were induced in the spleens of mice by the injection of antigen into the anterior chamber of an eye. Following this injection, the mice were immunized by the same antigen injected into the anterior chamber. Spleen cells recovered from these mice (AC-SPL cells) were titrated in an adoptive transfer assay to determine the number of AC-SPL cells required to effect a 50% reduction of antigen-induced swelling (Sw50) in the footpad of immunized mice challenged by antigen. RESULTS: Suppression of the expression of DTH is proportional to the number of AC-SPL cells injected into the site challenged by antigen. The number of AC-SPL cells required for a 50% reduction in DTH-induced swelling is reduced by injecting a cell population enriched for CD8(+) AC-SPL cells. Immunizing the mice receiving intracameral antigen to the same antigen decreases the RSw50 of AC-SPL cells required to inhibit the expression of DTH. CONCLUSIONS: The results provide the first quantitative demonstration that the numbers of antigen-specific splenic CD8(+) suppressor T cells are specifically amplified by antigen during an immune response

Variation in the solubilization of crude protein in wheat straw by different white-rot fungi

Besides their unique ability to depolymerize cell wall components, white-rot fungi are known to assimilate nitrogenous compounds from substrates. This modification may change protein solubility and fermentation in the rumen. To investigate this, the crude protein (CP) in fungal treated wheat straw (3 fungal species, 2 strains each) was fractioned according to the Cornell Net Carbohydrate and Protein System (CNCPS) and assessed for in vitro protein fermentation using a modified gas production technique (IVGPN). Results showed that fungi increased fraction A (instantaneously soluble CP; ∼2.6 times) and B1 (rapidly degradable; ∼1.2 times); and decreased the slowly degradable fraction B3 (∼41.6%) and unavailable fraction C (∼48.3%). The IVGPN of straw treated with Ceriporiopsis subvermispora strains were not different to the control, but increased by 30.2 to 47.1% in Pleurotus eryngii and Lentinula edodes strains. The IVGPN was significantly (P <  0.01) correlated to all fractions of CP, except fraction B1 and B2 (intermediately degradable). All fungi also increased the arginine (∼56%) and lysine (∼15%) contents. This study shows the importance of assessing the protein solubilization by different fungal strains, which can uncover unique mechanisms in the cell wall depolymerization