Withdrawal of parenteral phenobarbitone - Implications for resource-poor countries

Parenteral phenobarbitone is an integral part of the management of status epilepticus, especially in the context of resource-poor countries. It is highly effective at controlling seizures. It is safe, cheap, can be given by rapid intravenous push or intramuscular route, boluses can be repeated, and it is recommended as part of the Advanced Paediatric Life Support guidelines. The proposed alternatives lack efficacy, practicality and/or place the child in status epilepticus at risk of respiratory compromise. The impact of the loss of parenteral phenobarbitone would be increased cardiac complications, lack of early seizure control, prolonged seizures resulting in brain damage and systemic complications. Increased numbers of patients will require artificial ventilation in centres without facilities, and centres with facilities will be unable to cope with the load of ventilated patients because of lack of safe transport systems and bed space

The bending strength of tablets with a breaking line—Comparison of the results of an elastic and a "brittle cracking" finite element model with experimental findings

The aim of this work was to ascertain the influence of the position of the breaking line of bevel-edged tablets in a three-point bending test. Two different brands of commercially available, flat-round, bevel-edged tablets with a single central breaking line were studied. Breaking line positions tested, relative to the upper loading roll, were 0°, 22.5°, 45°, 67.5° and 90°. The breaking line faced either up- or downwards during the test. The practical results were compared with FEM results simulating similar test configurations. Tablets failed mainly across the failure plane, resulting in two tablet halves. An exception to this was found for tablets where the breaking line faced down and was positioned at an angle of 22.5° relative to the loading plane. Here the crack followed the breaking line in the centre of the tablets and only diverged towards the loading plane position at the edges of the tablets. The breaking line facing upwards resulted in a significantly higher tensile strength of the tablets compared to it facing downwards. However, with one exception, the orientation of the breaking line relative to the loading plane appeared not to affect the tensile strength values. A fully elastic FEM model indicated that both the position of the breaking line relative to the loading plane and as to whether the breaking line faced up- or downwards during the bending test would result in considerably different failure loads during practical experiments. The results also suggested that regardless of the breaking line position, when it is facing down crack propagation should start at the outer edges propagating towards the midpoint of the discs until failure occurs. Failure should hence always result in equal tablet halves, whereby the failure plane should coincide with the loading plane. Neither predictions fully reflected the practical behaviour of the tablets. Using a brittle cracking FEM model significantly larger tensile stresses for tablets with the breaking line positioned downwards at 0° or 22.5° relative to the loading plane were still predicted, but the differences between model and experimental values was greatly reduced. The remaining differences are more likely due to the inadequacy of the equation available to calculate the experimental tensile strength values. This equation cannot account for the presence of a breaking line and overestimates the thickness of the loading plane by the depth of the breaking line when in 0° or 22.5° position. If the depth of the breaking line is taken into account, the model predictions and the experimental findings are comparable. Also, in the brittle cracking FEM simulations the predicted crack propagation patterns were similar to those found in the experiments, and the model stress distributions across the lower surfaces were much more homogeneous and streamlined parallel to the loading plane. The brittle cracking model hence reflected the practicalities of the bending test more closely. The findings suggested that with the breaking line facing down fracture should always start in the centre of a tablet at its lower surface, initiated by the breaking line. Due to simultaneous development of larger stresses along the y-axis the tablet should still break into two equal halves along the loading plane, unless the position of the breaking line relative to the loading plane was 22.5°. In this case the tablet would fail by a mixed process, whereby failure would occur mainly along the breaking line, but due to simultaneous crack formation at the lower surface close to the bevel edge parallel to the loading plane the final breaking pattern would deviate from the breaking line about half-way from its centre, as seen in the practical experiments

Genetic Algorithm Performance with Different Selection Strategies in Solving TSP

A genetic algorithm (GA) has several genetic operators that can be modified to improve the performance of particular implementations. These operators include parent selection, crossover and mutation. Selection is one of the important operations in the GA process. There are several ways for selection. This paper presents the comparison of GA performance in solving travelling salesman problem (TSP) using different parent selection strategy. Several TSP instances were tested and the results show that tournament selection strategy outperformed proportional roulette wheel and rank-based roulette wheel selections, achieving best solution quality with low computing times. Results also reveal that tournament and proportional roulette wheel can be superior to the rank-based roulette wheel selection for smaller problems only and become susceptible to premature convergence as problem size increases

Detecting cell lysis using viscosity monitoring in E. coli fermentation to prevent product loss

Monitoring the physical or chemical properties of cell broths to infer cell status is often challenging due to the complex nature of the broth. Key factors indicative of cell status include cell density, cell viability, product leakage and DNA release to the fermentation broth. The rapid and accurate prediction of cell status for hosts with intracellular protein products can minimise product loss due to leakage at the onset of cell lysis in fermentation. This paper reports the rheological examination of an industrially relevant E. coli fermentation system producing antibody fragments (Fab'). Viscosity monitoring showed an increase in viscosity during the exponential phase in relation to the cell density increase; this is a relatively flat profile in the stationary phase, followed by a rapid increase which correlated well with product loss, DNA release and loss of cell viability. This phenomenon was observed over several fermentations that a 25% increase in broth viscosity (using induction-point viscosity as a reference) indicated 10% product loss. Our results suggest that viscosity can accurately detect cell lysis and product leakage in post-induction cell cultures, and can identify cell lysis earlier than several other common fermentation monitoring techniques. This work demonstrates the utility of rapidly monitoring the physical properties of fermentation broths, and that viscosity monitoring has the potential to be a tool for process development to determine the optimal harvest time and minimise product los

Investigating and modelling the effects of cell lysis on the rheological properties of fermentation broths

This article examines the rheology of an industrially relevant E. coli fermentation system producing antibody fragments (Fab′), to gain a deeper understanding of the physical properties of fermentation broths. Viscosity monitoring has been shown to be a useful tool to detect cell lysis and product leakage in late stage fermentation, and here we add to this work by characterising the rheological properties of an E. coli cell broth and its individual components, such as cell paste, supernatant, DNA and protein. Viscoelastic measurements have been carried out to provide novel insight into properties such as changes in cell strength, stability and robustness during fermentation, with ramifications for alternative process monitoring and control strategies. Additionally, an empirical model has been created to determine the extent of cell lysis using viscosity measurements, based on DNA leakage in late stage fermentation. The model directly indicates product loss to extracellular space, as intracellular content (product, DNA and host cell protein) is released simultaneously during cell lysis in late stage fermentation

Theoretical investigations into the influence of the position of a breaking line on the tensile failure of flat, round, bevel-edged tablets using finite element methodology (FEM) and its practical relevance for industrial tablet strength testing.

Flat, round tablets may have a breaking ("score") line. Pharmacopoeial tablet breaking load tests are diametral in their design, and industrially used breaking load testers often have automatic tablet feeding systems, which position the tablets between the loading platens of the machine with the breaking lines in random orientation to the applied load. The aim of this work was to ascertain the influence of the position of the breaking line in a diametral compression test using finite element methodology (FEM) and to compare the theoretical results with practical findings using commercially produced bevel-edged, scored tablets. Breaking line test positions at an angle of 0°, 22.5°, 45°, 67.5° and 90° relative to the loading plane were studied. FEM results obtained for fully elastic and elasto-plastic tablets were fairly similar, but they highlighted large differences in stress distributions depending on the position of the breaking line. The stress values at failure were predicted to be similar for tablets tested at an angle of 45° or above, whereas at lower test angles the predicted breaking loads were up to three times larger. The stress distributions suggested that not all breaking line angles would result in clean tensile failure. Practical results, however, did not confirm the differences in the predicted breaking loads, but they confirmed differences in the way tablets broke. The results suggest that it is not advisable to convert breaking loads obtained on scored tablets into tablet tensile strength values, and comparisons between different tablets or batches should carefully consider the orientation of the breaking line with respect to the loading plane, as the failure mechanisms appear to vary

Seroprevalence of HTLV-1 and HTLV-2 amongst mothers and children in Malawi within the context of a systematic review and meta-analysis of HTLV seroprevalence in Africa

OBJECTIVES: Human T‐lymphotropic virus (HTLV)‐1 causes T‐cell leukaemia and myelopathy. Together with HTLV‐2, it is endemic in some African nations. Seroprevalence data from Malawi are scarce, with no reports on associated disease incidence. HTLV seroprevalence and type were tested in 418 healthy mothers from Malawi. In addition, we tested the sera of 534 children to investigate mother‐to‐child transmission. To provide context, we conducted a systematic review and meta‐analysis of HTLV seroprevalence in African women and children. METHODS: Stored samples from a previous childhood cancer and BBV study were analysed. ELISA was used for HTLV screening followed by immunoblot for confirmation and typing. Standard methods were used for the systematic review. RESULTS: HTLV seroprevalence was 2.6% (11/418) in mothers and 2.2% (12/534) in children. Three mothers carried HTLV‐1 alone, seven had HTLV‐2 and one was dually infected. Three children carried HTLV‐1 alone, seven had HTLV‐2 and two were dually infected. Only two corresponding mothers of the 12 HTLV‐positive children were HTLV positive. The systematic review included 66 studies of women and 13 of children conducted in 25 African countries. Seroprevalence of HTLV‐1 varied from 0 to 17% and of HTLV‐2 from 0 to 4%. CONCLUSIONS: In contrast to findings from other studies in Africa, the seroprevalence of HTLV‐2 was higher than that of HTLV‐1 in Malawi and one of the highest for the African region. The lack of mother–child concordance suggests alternative sources of infection among children. Our data and analyses contribute to HTLV prevalence mapping in Africa

Epilepsy diagnosis and management of children in Kenya: review of current literature

Introduction: The growing impact of non-communicable diseases in low- to middle-income countries makes epilepsy a key research priority. We evaluated peer-reviewed published literature on childhood epilepsy specific to Kenya to identify knowledge gaps and inform future priorities. Methodology: A literature search utilizing the terms “epilepsy” OR “seizure” as exploded subject headings AND “Kenya” was conducted. Relevant databases were searched, generating 908 articles. After initial screening to remove duplications, irrelevant articles, and publications older than 15 years, 154 papers remained for full-article review, which identified 35 publications containing relevant information. Data were extracted from these reports on epidemiology, etiology, clinical features, management, and outcomes. Results: The estimated prevalence of lifetime epilepsy in children was 21–41 per 1,000, while the incidence of active convulsive epilepsy was 39–187 cases per 100,000 children per year. The incidence of acute seizures was 312–879 per 100,000 children per year and neonatal seizures 3,950 per 100,000 live births per year. Common risk factors for both epilepsy and acute seizures included adverse perinatal events, meningitis, malaria, febrile seizures, and family history of epilepsy. Electroencephalography abnormalities were documented in 20%–41% and neurocognitive comorbidities in more than half. Mortality in children admitted with acute seizures was 3%–6%, and neurological sequelae were identified in 31% following convulsive status epilepticus. Only 7%–29% children with epilepsy were on antiseizure medication. Conclusion: Active convulsive epilepsy is a common condition among Kenyan children, remains largely untreated, and leads to extremely poor outcomes. The high proportion of epilepsy attributable to preventable causes, in particular neonatal morbidity, contributes significantly to the lifetime burden of the condition. This review reaffirms the ongoing need for better public awareness of epilepsy as a treatable disease and for national-level action that targets both prevention and management