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Background Over the past years, there has been a growing concern that a considerable amount of anti-malarial supply in the underdeveloped world particularly in the private sector, is of poor quality. The World Health Organization (WHO) has received about 1500 reports that mentions instances of substandard and falsified products since 2013. The majority of the reports concerned antibiotics and anti-malarials. The majority of reports (42%) originate from the WHO African region. Objective This study intends to assess the quality of the most widely used anti-malarial medications [artemether-lumefantrine tablets, chloroquine phosphate tablets, primaquine phosphate tablets, artesunate, and artemether injections] in Gambella, South-West, Ethiopia. Methods A total of 52 samples were collected on June 2022 from Gambella National Regional State, Ethiopia. Half of the districts (six) located in the four zones of the region were chosen using simple random sampling technique. All drug retail outlets available in the selected districts (locally known as woredas) were included. The samples were subjected to visual inspection with a tool adopted from the joint WHO/FIP/ USP checklist. The pharmacopeial tests for identification, uniformity of dosage forms, assay, thickness, diameter, hardness, friability, disintegration test, dissolution, and sterility tests were carried out according to the USP 44-NF 39 and International Pharmacopoeia 11th edition, 2022 monographs. Results and Discussion Only 25% of the samples were registered on the Ethiopian Food and Drug Authority (EFDA’s) electronic regulatory/ registration system (ERIS). Besides, 88.8% of artemether injection products were presented in clear glass ampoules. This might expose the products to photochemical degradation that leads to in loss of anti-plasmodial activity. In addition, 50% of the artemether products assessed were not bioequivalent with the comparator product in the in vitro dissolution comparison tests. Overall, the study findings reveal a high prevalence (58.3%) of substandard anti-malarial drugs in the region. The stated percent of the samples had failed in one or more of the quality test parameters assessed in this study. Conclusion The study findings reveal a high prevalence (58.3%) of substandard anti-malarial drugs in the region. Only a quarter were registered and 38% of the unregistered products failed the quality tests. Hence, the national, regional medicine regulatory bodies and other stake holders should perform the required roles to circumvent presence of Substandard and Falsified (SF) anti-malarial drugs in the study sites.

This study aimed to clarify the relationship between carbapenem consumption and clinical outcome using the diagnosis procedure combination (DPC) payment system database (2020) published by the Ministry of Health, Labour, and Welfare of Japan. This study divided 5316 medical facilities subject to aggregation into five facilities and calculated the median values, including facility characteristics, clinical outcomes, and carbapenem consumption. Next, a correlation analysis was performed between carbapenem consumption and clinical outcome, as well as a multiple regression analysis between carbapenem consumption as the dependent variable and clinical outcome, bed size, and proportion of patients by disease as independent variables. Additionally, three clinical outcomes available from the DPC payment system database were selected, including cure, readmission within 4 weeks, and the average length of stay. This study revealed no relationship between carbapenem consumption and clinical outcome in university hospitals and university hospital-equivalent community hospitals; however, a relationship was suggested in the community, DPC-prepared, and non-DPC hospitals. University hospitals and university hospital-equivalent community hospitals with a high consumption of carbapenems may need to reconsider the classification because of the limited number of facilities in this classification.

Background Substandard anti-malarial agents pose a significant challenge to effective malaria control and elimination efforts especially in sub-Saharan Africa. The quality of anti-malarials in most low-and-middle income countries (LMICs) is affected by several factors including inadequate regulation and limited resources. In this study, the pharmacopeial quality of artemether–lumefantrine (AL) in low and high malaria transmission settings in Uganda was assessed. Methods This was a cross-sectional study conducted among randomly selected private drug outlets. The AL anti-malarials available in drug outlets were purchased using overt method. The samples were screened for quality using visual inspection, weight uniformity, content assay and dissolution tests. The assay test was done using liquid chromatography–mass spectrometry (LC–MS). The samples were considered substandard if the active pharmaceutical ingredient (API) content was outside 90–110% range of the label claim. Dissolution test was conducted following United States Pharmacopoeia (USP) method. Data was analysed using descriptive statistics and presented as means with standard deviations, frequencies, and proportions. Correlation between medicine quality and independent variables was determined using Fisher’s exact test of independence at 95% level of significance. Results A total of 74 AL anti-malarial samples were purchased from high (49/74; 66.2%) and low (25/74; 33.8%) malaria transmission settings. The most common batch of AL was LONART, 32.4% (24/74), with 33.8% (25/74) being ‘Green leaf’. Overall prevalence of substandard quality artemether–lumefantrine was 18.9% (14/74; 95% CI: 11.4–29.7). Substandard quality AL was significantly associated with setting ( p  = 0.002). A total of 10 samples (13.5%) failed artemether content assay test while, 4 samples (5.4%, 4/74) failed the lumefantrine assay test. One sample from a high malaria transmission setting failed both artemether and lumefantrine assay content test. Of the samples that failed artemether assay test, 90% had low (< 90%) artemether content. All the samples passed visual inspection and dissolution tests. Conclusion Artemether–lumefantrine agents, the recommended first-line treatment for uncomplicated malaria with APIs outside the recommended pharmacopeial content assay limit is common especially in high malaria transmission settings. There is need for continuous surveillance and monitoring of the quality of artemisinin-based anti-malarials across the country by the drug regulatory agency.

Two green analytical approaches have been developed for the analysis of antimalarial fixed dose tablets of artemether and lumefantrine for quality control. The first approach consisted of investigating the qualitative performance of a low-cost handheld near-infrared spectrometer in combination with the principal component analysis as an exploratory tool to identify trends, similarities, and differences between pharmaceutical samples, before applying the data driven soft independent modeling of class analogy (DD-SIMCA) as a one-class classifier for proper drug falsification detection with 100% of both sensitivity and specificity in the studied cases. Despite its limited spectral range and low resolution, the handheld device allowed detecting falsified drugs with no active pharmaceutical ingredient and identifying specifically a pharmaceutical tablet brand name. The second approach was the quantitative analysis based on the green and fast RP-HPLC technique using ethanol as a green organic solvent and acetic acid as a green pH modifier. The optimal separation was achieved in 7 min using a mobile phase composed of ethanol 96% and 10 mM of acetic acid pH 3.35 (63:37, v/v). The developed method was validated according to the total error approach based on an accuracy profile, was applied to the analysis of tablets, and allowed confirming falsified drugs detected by spectroscopy.

In tertiary education, assessment plays a critical role in shaping student engagement and measuring learning outcomes. In introductory statistics courses, understanding earlier material is essential for later topics, necessitating consistent engagement to avoid fragmented learning. Assessment influences motivation and the depth of conceptual understanding upon course completion. Traditional methods such as cumulative grading and learning analytics often fail to capture the complexity of student knowledge. This research employed a multi-layered approach, including innovative 'consistency of learning', 'combination analysis' and 'heatmap' techniques, to examine performance across 11 learning modules. Results showed that Pass-grade (50-64%) students often did not complete key modules adequately, resulting in fragmented understanding. The study highlighted the limitations of traditional evaluation methods in capturing the complexity and variability of student knowledge. It further emphasized the importance of thoughtful assessment design to ensure that students developed a cohesive understanding of the material regardless of the grade level they achieve. Given the increasing importance of statistical literacy in today's data-centric society, it is vital to equip students with the knowledge to make informed data decisions. By integrating these novel evaluation methods, educators can better understand and support student achievement and improve learning outcomes in introductory statistics.

Grain shape is an important agronomic character of rice, which affects the appearance, processing, and the edible quality. Screening and identifying more new genes associated with grain shape is beneficial to further understanding the genetic basis of grain shape and provides more gene resources for genetic breeding. This study has a natural population containing 623 indica rice cultivars. Genome-wide association studies/GWAS of several traits related to grain shape (grain length/GL, grain width/GW, grain length to width ratio/GLWR, grain circumferences/GC, and grain size/grain area/GS) were conducted by combining phenotypic data from four environments and the second-generation resequencing data, which have identified 39 important Quantitative trait locus/QTLs. We analyzed the 39 QTLs using three methods: gene-based association analysis, haplotype analysis, and functional annotation and identified three cloned genes (GS3, GW5, OsDER1) and seven new candidate genes in the candidate interval. At the same time, to effectively utilize the genes in the grain shape-related gene bank, we have also analyzed the allelic combinations of the three cloned genes. Finally, the extreme allele combination corresponding to each trait was found through statistical analysis. This study’s novel candidate genes and allele combinations will provide a valuable reference for future breeding work.

Keywords: Augmented renal clearance, Piperacillin, Critical care

Given the frequent initiation of antibacterial treatment at home by caregivers of children under five years in low-income countries, there is a need to find out whether caregivers' reports of prior antibacterial intake by their children before being brought to the healthcare facility are accurate. The aim of this study was to describe and validate caregivers' reported use of antibacterials by their children prior to seeking care at the healthcare facility. A cross sectional study was conducted among children under five years seeking care at healthcare facilities in Gulu district, northern Uganda. Using a researcher administered questionnaire, data were obtained from caregivers regarding reported prior antibacterial intake in their children. These reports were validated by comparing them to common antibacterial agents detected in blood and urine samples from the children using liquid chromatography with tandem mass spectrometry (LC-MS/MS) methods. A total of 355 study participants had a complete set of data on prior antibacterial use collected using both self-report and LC-MS/MS. Of the caregivers, 14.4% (51/355, CI: 10.9-18.5%) reported giving children antibacterials prior to visiting the healthcare facility. However, LC-MS/MS detected antibacterials in blood and urine samples in 63.7% (226/355, CI: 58.4-68.7%) of the children. The most common antibacterials detected from the laboratory analysis were cotrimoxazole (29%, 103/355), ciprofloxacin (13%, 46/355), and metronidazole (9.9%, 35/355). The sensitivity, specificity, positive predictive value (PPV), negative predictive value and agreement of self-reported antibacterial intake prior to healthcare facility visit were 17.3% (12.6-22.8), 90.7% (84.3-95.1), 76.5% (62.5-87.2), 38.5% (33.0-44.2) and 43.9% (k 0.06) respectively. There is low validity of caregivers' reports on prior intake of antibacterials by these children. There is need for further research to understand the factors associated with under reporting of prior antibacterial use.

Multi drug treatments are increasingly used in the clinic to combat complex and co-occurring diseases. However, most drug combination discovery efforts today are mainly focused on anticancer therapy and rarely examine the potential of using more than two drugs simultaneously. Moreover, there is currently no reported methodology for performing second- and higher-order drug combination analysis of secretomic patterns, meaning protein concentration profiles released by the cells. Here, we introduce COMBSecretomics (https://github.com/EffieChantzi/COMBSecretomics.git), the first pragmatic methodological framework designed to search exhaustively for second- and higher-order mixtures of candidate treatments that can modify, or even reverse malfunctioning secretomic patterns of human cells. This framework comes with two novel model-free combination analysis methods; a tailor-made generalization of the highest single agent principle and a data mining approach based on top-down hierarchical clustering. Quality control procedures to eliminate outliers and non-parametric statistics to quantify uncertainty in the results obtained are also included. COMBSecretomics is based on a standardized reproducible format and could be employed with any experimental platform that provides the required protein release data. Its practical use and functionality are demonstrated by means of a proof-of-principle pharmacological study related to cartilage degradation. COMBSecretomics is the first methodological framework reported to enable secretome-related second- and higher-order drug combination analysis. It could be used in drug discovery and development projects, clinical practice, as well as basic biological understanding of the largely unexplored changes in cell-cell communication that occurs due to disease and/or associated pharmacological treatment conditions.

Background Substandard and falsified anti-malarial medicines pose a serious threat to public health, especially in low-income countries. Appropriate technologies for drug quality analysis in resource-limited settings are important for the surveillance of the formal and informal drug market. The feasibility of thin-layer chromatography (TLC) with different solvent systems was tested using the GPHF Minilab in a study of the quality of sulfadoxine/pyrimethamine tablets in Malawi. Methods Twenty eight samples of sulfadoxine/pyrimethamine tablets were collected from randomly selected health facilities of four districts of southern Malawi. A mystery shopper approach was used when collecting samples from illegal street vendors, and an overt approach for the other facilities. Samples were subjected to visual inspection, disintegration testing and TLC analysis. 10 samples were further investigated according to the methods of the US Pharmacopeia using high performance liquid chromatography (HPLC). Results One sample was found to be falsified, containing a mixture of paracetamol tablets and co-trimoxazole tablets. These had been repackaged into paper strip packs labelled as a brand of sulfadoxine/pyrimethamine. TLC with different solvent systems readily proved that these tablets did not comply with their declaration, and provided strong evidence for the active pharmaceutical ingredients which were actually contained. Full pharmacopeial analysis by HPLC confirmed the results suggested by TLC for this sample, and showed two further samples to be of substandard quality. Conclusions Due to the absence of the declared anti-malarial ingredients and due to the presence of other pharmaceutical ingredients, the identified falsified medicine represents a serious health risk for the population. Thin-layer chromatography (TLC) using different solvent systems proved to be a powerful method for the identification of this type of counterfeiting, presenting a simple and affordable technology for use in resource-limited settings.