MOLECULAR DOCKING AND PHARMACOKINETIC PREDICTION OF HERBAL DERIVATIVES AS MALTASE-GLUCOAMYLASE INHIBITOR

  Objective: To perform molecular docking and pharmacokinetic prediction of momordicoside F2, beta-sitosterol, and cis-N-feruloyltyramine herbal derivatives as maltase-glucoamylase (MGAM) inhibitors for the treatment of diabetes.Methods: The herbal derivatives and standard drug miglitol were docked differently onto MGAM receptor using AutoDock Vina software. In addition, Lipinski's rule, drug-likeness, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties were analyzed using Molinspiration, ADMET structure–activity relationship, and prediction of activity spectra for substances online tools.Results: Docking studies reveal that momordicoside F2, beta-sitosterol, and cis-N-feruloyltyramine derivatives have high binding affinity to the MGAM receptor (−7.8, −6.8, and −6.5 Kcal/Mol, respectively) as compared to standard drug miglitol (−5.3 Kcal/Mol). In addition, all the herbal derivatives indicate good bioavailability (topological polar surface area <140 Ȧ and Nrot <10) without toxicity or mutagenic effects.Conclusion: The molecular docking and pharmacokinetic information of herbal derivatives obtained in this study can be utilized to develop novel MGAM inhibitors having antidiabetic potential with better pharmacokinetic and pharmacodynamics profile

Multiple testing of composite null hypotheses for discrete data using randomized pp-values

$P$-values that are derived from continuously distributed test statistics are typically uniformly distributed on $(0,1)$ under least favorable parameter configurations (LFCs) in the null hypothesis. Conservativeness of a $p$-value $P$ (meaning that $P$ is under the null hypothesis stochastically larger than a random variable which is uniformly distributed on $(0,1)$) can occur if the test statistic from which $P$ is derived is discrete, or if the true parameter value under the null is not an LFC. To deal with both of these sources of conservativeness, we present two approaches utilizing randomized $p$-values, namely single-stage and two-stage randomization. We illustrate their effectiveness for testing a composite null hypothesis under a binomial model. We also give an example of how the proposed $p$-values can be used to test a composite null in group testing designs. Similar to previous findings, we find that the proposed randomized $p$-values are less conservative compared to non-randomized $p$-values under the null hypothesis, but that they are stochastically not smaller under the alternative. The problem of establishing the validity of randomized $p$-values is not trivial and has received attention in previous literature. We show that our proposed randomized $p$-values are valid under various discrete statistical models which are such that the distribution of the corresponding test statistic belongs to an exponential family. The behaviour of the power function for the tests based on the proposed randomized $p$-values as a function of the sample size is also investigated. Simulations and a real data analysis are used to compare the different considered $p$-values

E-Learners’ Challenges and Coping Strategies in Interactive and Collaborative e-Learning in Kenya

Some universities in Kenya have taken up e-learning to flexibly deliver learning and bridge the educational access gap. Despite the benefits that e-learning offers to the e-learners, there are challenges that they must cope with. The aim of this paper is to present the challenges that emerged from a research that was undertaken in two Institutions of Higher Learning (IHLs). It also presents the coping strategies that e-learners used to overcome the challenges. The research used the constructivist version of Grounded Theory (GT) methodology. It used in-depth interviews and participant observations to gather data from the e-learners, e-tutors, e-learning managers and e-learning platforms. Therefore, the research yielded qualitative data which was analyzed using Atlas.ti software. Data was analyzed thematically to establish the patterns of challenges and the equivalent coping strategies. The results are presented using the Gioia technique and the discussion used the vignettes technique from participants in order to preserve their voice. The challenges that emerged relate to: e-content, coursework, internet access, e-learning technology, Information and Communication Technology (ICT) skills and training, interaction and collaboration, personal issues, teaching of Science, Technology, Engineering and Mathematics (STEM) courses and the tutorials. Recommendations on how to tackle these challenges have also been suggested. An understanding of these challenges is important to the e-learning players so that they can adopt interventions to mitigate them and hence improve interaction and collaboration. The results presented in this paper are part of the larger research whose main objective was to develop an e-learning theory for interaction and collaboration

Event and Actors Representation in Selected Nigerian Daily Newspapers

The 2011 Nigerian presidential election newspaper reports were not just to inform the public about the outcomes of the election. The representations in the newspaper reports were ideological and, by implication, judgmental. The main actors (presidential aspirants), were also represented differently. In this paper, we interrogate some linguistic tools that were used in the ideological presentation of the election and the main social actors. In other words, the paper examines whether the main social actors are included or excluded, genericised or specified; and the level of voice projection accorded to them. The study is anchored on Critical Discourse Analysis framework and it operationalises some aspects of van Leeuwen (2008) socio-semantic model and Hallidayan transitivity system in examining social actor differential representations and process types in the newspaper reports. These linguistic tools (exclusion, inclusion, individualization, assimilation, collectivization, functionalisation, appraisement and voice projection) are very pertinent because they serve as the very foundation on which further context analysis of the discourse could be based. The study observes that social actors representations and voice projection in the data do not only polarize the reportage but also lace it with bias. It also shows that the incumbent president was given more positive representation and voice projection than other aspirants

Making Urban Slum Population Visible: Citizens and Satellites to Reinforce Slum Censuses

In response to the “Leave No One Behind” principle (the central promise of the 2030 Agenda for Sustainable Development), reliable estimate of the total number of citizens living in slums is urgently needed but not available for some of the most vulnerable communities. Not having a reliable estimate of the number of poor urban dwellers limits evidence-based decision-making for proper resource allocation in the fight against urban inequalities. From a geographical perspective, urban population distribution maps in many low- and middle-income cities are most often derived from outdated or unreliable census data disaggregated by coarse administrative units. Moreover, slum populations are presented as aggregated within bigger administrative areas, leading to a large diffuse in the estimates. Existing global and open population databases provide homogeneously disaggregated information (i.e. in a spatial grid), but they mostly rely on census data to generate their estimates, so they do not provide additional information on the slum population. While a few studies have focused on bottom-up geospatial models for slum population mapping using survey data, geospatial covariates, and earth observation imagery, there is still a significant gap in methodological approaches for producing precise estimates within slums. To address this issue, we designed a pilot experiment to explore new avenues. We conducted this study in the slums of Nairobi, where we collected in situ data together with slum dwellers using a novel data collection protocol. Our results show that the combination of satellite imagery with in situ data collected by citizen science paves the way for generalisable, gridded estimates of slum populations. Furthermore, we find that the urban physiognomy of slums and population distribution patterns are related, which allows for highlighting the diversity of such patterns using earth observation within and between slums of the same city

Mobile phone-delivered reminders and incentives to improve childhood immunisation coverage and timeliness in Kenya (M-SIMU): a cluster randomised controlled trial

Background As mobile phone access continues to expand globally, opportunities exist to leverage these technologies to support demand for immunisation services and improve vaccine coverage. We aimed to assess whether short message service (SMS) reminders and monetary incentives can improve immunisation uptake in Kenya. Methods In this cluster-randomised controlled trial, villages were randomly and evenly allocated to four groups: control, SMS only, SMS plus a 75 Kenya Shilling (KES) incentive, and SMS plus 200 KES (85 KES = USD$1). Caregivers were eligible if they had a child younger than 5 weeks who had not yet received a first dose of pentavalent vaccine. Participants in the intervention groups received SMS reminders before scheduled pentavalent and measles immunisation visits. Participants in incentive groups, additionally, received money if their child was timely immunised (immunisation within 2 weeks of the due date). Caregivers and interviewers were not masked. The proportion of fully immunised children (receiving BCG, three doses of polio vaccine, three doses of pentavalent vaccine, and measles vaccine) by 12 months of age constituted the primary outcome and was analysed with logbinomial regression and General Estimating Equations to account for correlation within clusters. This trial is registered with ClinicalTrials.gov, number NCT01878435. Findings Between Oct 14, 2013, and Oct 17, 2014, we enrolled 2018 caregivers and their infants from 152 villages into the following four groups: control (n=489), SMS only (n=476), SMS plus 75 KES (n=562), and SMS plus 200 KES (n=491). Overall, 1375 (86%) of 1600 children who were successfully followed up achieved the primary outcome, full immunisation by 12 months of age (296 [82%] of 360 control participants, 332 [86%] of 388 SMS only participants, 383 [86%] of 446 SMS plus 75 KES participants, and 364 [90%] of 406 SMS plus 200 KES participants). Children in the SMS plus 200 KES group were significantly more likely to achieve full immunisation at 12 months of age (relative risk 1·09, 95% CI 1·02–1·16, p=0·014) than children in the control group. Interpretation In a setting with high baseline immunisation coverage levels, SMS reminders coupled with incentives significantly improved immunisation coverage and timeliness. Given that global immunisation coverage levels have stagnated around 85%, the use of incentives might be one option to reach the remaining 15%

Impact of intermittent preventive treatment of malaria in pregnancy with dihydroartemisinin-piperaquine versus sulfadoxine-pyrimethamine on the incidence of malaria in infancy: a randomized controlled trial.

BACKGROUND: Intermittent preventive treatment of malaria during pregnancy (IPTp) with dihydroartemisinin-piperaquine (DP) significantly reduces the burden of malaria during pregnancy compared to sulfadoxine-pyrimethamine (SP), the current standard of care, but its impact on the incidence of malaria during infancy is unknown. METHODS: We conducted a double-blind randomized trial to compare the incidence of malaria during infancy among infants born to HIV-uninfected pregnant women who were randomized to monthly IPTp with either DP or SP. Infants were followed for all their medical care in a dedicated study clinic, and routine assessments were conducted every 4 weeks. At all visits, infants with fever and a positive thick blood smear were diagnosed and treated for malaria. The primary outcome was malaria incidence during the first 12 months of life. All analyses were done by modified intention to treat. RESULTS: Of the 782 women enrolled, 687 were followed through delivery from December 9, 2016, to December 5, 2017, resulting in 678 live births: 339 born to mothers randomized to SP and 339 born to those randomized to DP. Of these, 581 infants (85.7%) were followed up to 12 months of age. Overall, the incidence of malaria was lower among infants born to mothers randomized to DP compared to SP, but the difference was not statistically significant (1.71 vs 1.98 episodes per person-year, incidence rate ratio (IRR) 0.87, 95% confidence interval (CI) 0.73-1.03, p = 0.11). Stratifying by infant sex, IPTp with DP was associated with a lower incidence of malaria among male infants (IRR 0.75, 95% CI 0.58-0.98, p = 0.03) but not female infants (IRR 0.99, 95% CI 0.79-1.24, p = 0.93). CONCLUSION: Despite the superiority of DP for IPTp, there was no evidence of a difference in malaria incidence during infancy in infants born to mothers who received DP compared to those born to mothers who received SP. Only male infants appeared to benefit from IPTp-DP suggesting that IPTp-DP may provide additional benefits beyond birth. Further research is needed to further explore the benefits of DP versus SP for IPTp on the health outcomes of infants. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02793622 . Registered on June 8, 2016

Sampling-Based Approaches to Improve Estimation of Mortality among Patient Dropouts: Experience from a Large PEPFAR-Funded Program in Western Kenya

Monitoring and evaluation (M&E) of HIV care and treatment programs is impacted by losses to follow-up (LTFU) in the patient population. The severity of this effect is undeniable but its extent unknown. Tracing all lost patients addresses this but census methods are not feasible in programs involving rapid scale-up of HIV treatment in the developing world. Sampling-based approaches and statistical adjustment are the only scaleable methods permitting accurate estimation of M&E indices.In a large antiretroviral therapy (ART) program in western Kenya, we assessed the impact of LTFU on estimating patient mortality among 8,977 adult clients of whom, 3,624 were LTFU. Overall, dropouts were more likely male (36.8% versus 33.7%; p = 0.003), and younger than non-dropouts (35.3 versus 35.7 years old; p = 0.020), with lower median CD4 count at enrollment (160 versus 189 cells/ml; p<0.001) and WHO stage 3-4 disease (47.5% versus 41.1%; p<0.001). Urban clinic clients were 75.0% of non-dropouts but 70.3% of dropouts (p<0.001). Of the 3,624 dropouts, 1,143 were sought and 621 had their vital status ascertained. Statistical techniques were used to adjust mortality estimates based on information obtained from located LTFU patients. Observed mortality estimates one year after enrollment were 1.7% (95% CI 1.3%-2.0%), revised to 2.8% (2.3%-3.1%) when deaths discovered through outreach were added and adjusted to 9.2% (7.8%-10.6%) and 9.9% (8.4%-11.5%) through statistical modeling depending on the method used. The estimates 12 months after ART initiation were 1.7% (1.3%-2.2%), 3.4% (2.9%-4.0%), 10.5% (8.7%-12.3%) and 10.7% (8.9%-12.6%) respectively. CONCLUSIONS/SIGNIFICANCE ABSTRACT: Assessment of the impact of LTFU is critical in program M&E as estimated mortality based on passive monitoring may underestimate true mortality by up to 80%. This bias can be ameliorated by tracing a sample of dropouts and statistically adjust the mortality estimates to properly evaluate and guide large HIV care and treatment programs