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

Entrained defects and mechanical properties of aluminium castings

The presence of entrained double oxide films, known as bifilms, has been identified as a contributing factor to the variability in mechanical properties observed in aluminium castings. These bifilms consist of folded-over oxide films containing gas-filled crevices and are formed due to turbulence on the liquid metal's surface during handling and pouring. Additionally, it has been suggested that hydrogen dissolved in the aluminium melt can permeate these defects, causing them to expand and leading to the formation of hydrogen porosity. This, in turn, exacerbates the detrimental effects on the mechanical properties of the castings. In this study, the ultimate tensile strength (UTS) and percentage elongation of sand cast bars were compared under various casting conditions. These parameters were chosen as indicators of casting reliability, which was expected to be influenced by the presence of oxide films. The results indicated that incorporating filters in the gating system and reducing the runner height led to a noticeable improvement in tensile strength and elongation. This improvement was attributed to enhanced mold filling conditions, which reduced the likelihood of oxide film entrainment. The findings of this research provide valuable insights into the factors that affect the properties of light metal alloy castings. By understanding these influences, it becomes possible to develop improved practices that result in healthier castings with enhanced mechanical properties

Effect of runner thickness and hydrogen content on the mechanical properties of A356 alloy castings

Earlier studies demonstrated the detrimental effect of entrained bifilm defects on aluminum cast alloys’ tensile and fatigue properties. It was suggested that hydrogen has a contributing role as it diffuses into the bifilms and swells them out to form hydrogen porosity. In this study, the effect of the runner height and hydrogen content on the properties of A356 alloy castings was investigated using a two-level full factorial design of experiments. Four responses, the Weibull modulus and position parameter of both the ultimate tensile strength (UTS) and % elongation, were assessed. The results suggested that decreasing the runner height and adopting procedures intended to decrease the hydrogen content of the casting caused a considerable enhancement of the Weibull moduli and position parameters of the UTS and % elongation. This was reasoned to the more quiescent practice during mold filling, eliminating the possibility of bifilm formation as well as the decreased hydrogen level that eliminated the amount of hydrogen diffused into the bifilms and accordingly decreased the size of the entrained defects. This, in turn, would allow the production of A356 cast alloys with better and more reproducible properties

Influence of bifilm defects generated during mould filling on the tensile properties of Al–Si–Mg cast alloys

Entrapped double oxide film defects are known to be the most detrimental defects during the casting of aluminium alloys. In addition, hydrogen dissolved in the aluminium melt was suggested to pass into the defects to expand them and cause hydrogen porosity. In this work, the effect of two important casting parameters (the filtration and hydrogen content) on the properties of Al–7 Si–0.3 Mg alloy castings was studied using a full factorial design of experiments approach. Casting properties such as the Weibull modulus and position parameter of the elongation and the tensile strength were considered as response parameters. The results suggested that adopting 10 PPI filters in the gating system resulted in a considerable boost of the Weibull moduli of the tensile strength and elongation due to the enhanced mould filling conditions that minimised the possibility of oxide film entrainment. In addition, the results showed that reducing the hydrogen content in the castings samples from 0.257 to 0.132 cm3/100 g Al was associated with a noticeable decrease in the size of bifilm defects with a corresponding improvement in the mechanical properties. Such significant effect of the process parameters studied on the casting properties suggests that the more careful and quiescent mould filling practice and the lower the hydrogen level of the casting, the higher the quality and reliability of the castings produced

Myelodysplasia in a psoriasis patient receiving etanercept : Cause or coincidence?

Peer reviewedFinal Accepted Versio

Hibiscus sabdariffa Affects Ammonium Chloride-Induced Hyperammonemic Rats

Hibiscus sabdariffa (HS) is an edible medicinal plant, indigenous to India, China and Thailand and is used in Ayurveda and traditional medicine. Alcoholic extract of HS leaves (HSEt) was studied for its anti-hyperammonemic and antioxidant effects in brain tissues of ammonium chloride-induced hyperammonemic rats. Oral administration of HSEt (250 mg kg−1 body weight) significantly normalizes the levels of ammonia, urea, uric acid, creatinine and non-protein nitrogen in the blood. HSEt significantly reduced brain levels of lipid peroxidation products such as thiobarbituric acid and reactive substances (TBARS) and hydroperoxides (HP). However, the administered extract significantly increased the levels of antioxidants such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and reduced glutathione (GSH) in brain tissues of hyperammonemic rats. This investigation demonstrates significant anti-hyperammonemic and antioxidant activity of HS

Optimisation of a novel hot air contactless single incremental point forming of polymers

This study presents a new contactless sheet forming method that utilises hot air as a forming tool to address tool wear challenges in single-point incremental forming. Experiments were conducted on a 3-axis CNC machine equipped with a hot air nozzle on a polycarbonate sheet. A design of experiment (DOE) approach was employed, evaluating five control factors: air pressure, air temperature, feed rate, tool offset, and step down. The evaluation criteria for the formed sheets are profile variation, thickness variation, and surface roughness. The results indicate that air temperature and feed rate have the most significant influence on the deformation process. Additionally, air pressure and feed rate substantially impact both thickness variation and surface roughness of the formed material. To optimise the process parameters for high-quality forming, a prediction model is developed. The optimised process shows good agreement with the predicted model regarding profile and thickness variations. However, it does not align with surface roughness due to the stepwise nature and inherent waviness of the contactless forming technique. This study offers a promising approach for developing innovative contactless forming techniques using hot pressurised air as a forming tool. The proposed technique has the potential to significantly reduce tool wear and lubrication requirements

Retinopathy of prematurity in infants with birth weight above 1500 grams

Objective: To identify the rate and prognosis of retinopathy of prematurity (ROP) among newborn infants of birthweight of above 1500 grams, and the possible risk factors associated with the disease.Design: A prospective cohort study.Setting: Neonatal unit at Maternity Hospital, Kuwait city, Kuwait.Methods: All low birth weight infants were examined for the presence of ROP in the period between January 1996 to December 1997. Prospective collection of data on babies who were above 1500 grams was done to find an association between the disease in these babies and some of the maternal and neonatal risk factors.Results: A total of 68 babies of birth weight above 1500 grams were screened for ROP out of which 13 (19.1%) had different stages of the disease. None of the patients had threshold disease requiring surgery. Among the risk factors chosen, oxygen therapy, presence ofhypotension at birth and the non-use of surfactant were the only risk factors to be associated with disease. However, with logistic regression analysis, none of these were independently associated with ROP.Conclusion: ROP may occur in newborn infants of larger birthweight but with good prognosis, and oxygen therapy seems to predispose to the disease

Hot-air contactless single-point incremental forming

Single-point incremental forming (SPIF) has emerged as a time-efficient approach that offers increased material formability compared to conventional sheet-metal forming techniques. However, the physical interaction between the forming tool and the sheet poses challenges, such as tool wear and formability limits. This study introduces a novel sheet-forming technique called contactless single-point incremental forming (CSPIF), which uses hot compressed air as a deformation tool, eliminating the requirement for physical interaction between the sheet and a rigid forming tool. In this study, a polycarbonate sheet was chosen as the case-study material and subjected to the developed CSPIF. The experiments were carried out at an air temperature of 160 °C, air pressure of 1 bar, a nozzle speed of 750 mm/min, and a step-down thickness of 0.75 mm. A Schlieren setup and a thermal camera were used to visualize the motion of the compressed hot air as it traveled from the nozzle to the sheet. The results showed that the CSPIF technique allowed for the precise shaping of the polycarbonate sheet with minimal springback. However, minor deviations from the designed profile were observed, primarily at the starting point of the nozzle, which can be attributed to the bending effects of the sample. In addition, the occurrence of sheet thinning and material buildup on the deformed workpiece was also observed. The average surface roughness (Ra) of the deformed workpiece was measured to be 0.2871 micron

SPACE VECTOR PWM TECHNIQUE FOR THREE- TO SEVEN-PHASE AC-TO-AC POWER CONVERTERS: ANALYSIS AND EXPERIMENTAL VERIFICATIONS

This paper presents Pulse Width Modulation (PWM) control technique for three to seven-phase ac-to-ac power converters. These proposed PWM techniques are based on Indirect Space Vector Modulation (ISVM), which model the converter as two independent stages perform rectification and inversion stages. Two schemes of ISVM are proposed. The first scheme maximizes the voltage transfer ratio (VTR) of the converter but it produces unwanted low order harmonics. The second scheme generates sinusoidal output voltage waveforms; the cost is a reduction in the VTR of this configuration in linear mode. The viability of the proposed technique is proved using experimental results