Quantitative feature extraction for machine learning analysis of resting-state fMRI data

Joint posterior distributions of the fitted statistical models. (DOCX 32 kb

Effect of dolutegravir on folate, vitamin B12 and mean corpuscular volume levels among children and adolescents with HIV: a sub‐study of the ODYSSEY randomized controlled trial

INTRODUCTION: Dolutegravir-based antiretroviral therapy (ART) is the preferred antiretroviral treatment for children and adolescents living with HIV. A large surveillance study in Botswana previously raised concerns about an association between pre-conception dolutegravir and neural tube defects. Before these concerns were subsequently resolved, we set up a sub-study to look at the effect of dolutegravir on levels of folate and vitamin B12 in children and adolescents within the randomized ODYSSEY trial, as folate and vitamin B12 are known to play a crucial role in neural tube development. METHODS: We conducted the sub-study among Ugandan ODYSSEY participants and compared folate and vitamin B12 between children randomized to dolutegravir-based ART (DTG) and non-dolutegravir-based standard-of-care treatment (SOC). Plasma folate was measured at enrolment and week 4 on stored samples; in addition, plasma and red blood cell (RBC) folate and vitamin B12 were assayed at week ≥96 in prospectively collected samples. RBC mean corpuscular volume (MCV) was measured 24-weekly in all ODYSSEY participants. Samples analysed in the sub-study were collected between September 2016 and October 2020. RESULTS: A total of 229 children aged ≥6 years were included in the sub-study with median age at trial enrolment of 12.3 (interquartile range [IQR] 9.0, 14.7) years, and CD4 count of 501 (IQR 228, 695); 112 (49%) children were male. Most participants (225/229, 98%) had plasma folate results at enrolment and 214 (93%) children had results available for RBC folate, vitamin B12 and plasma folate at week ≥96. MCV results were analysed on 679 children aged ≥6 years enrolled in ODYSSEY. At week 4, mean plasma folate was significantly higher in the dolutegravir arm than in SOC (difference [DTG-SOC] 1.6 ng/ml, 95% CI 0.8, 2.3; p<0.001), and this difference persisted to week ≥96 (2.7 ng/ml, 95% CI 1.7, 3.7; p<0.001). Mean RBC folate at ≥96 weeks was also higher in the DTG arm (difference 73 ng/ml, 95% CI 3, 143; p = 0.041). There was no difference in the treatment arms for vitamin B12 levels at ≥96 weeks or change in MCV through trial follow-up. CONCLUSIONS: Plasma and RBC folate levels were higher in children and adolescents receiving dolutegravir-based ART than on other ART regimens. Further studies are needed to clarify the mechanisms of these interactions and the clinical implications of increased blood folate levels

Molecular surveillance reveals the presence of pfhrp2 and pfhrp3 gene deletions in Plasmodium falciparum parasite populations in Uganda, 2017–2019

Abstract Background Histidine-rich protein-2 (HRP2)-based rapid diagnostic tests (RDTs) are the only RDTs recommended for malaria diagnosis in Uganda. However, the emergence of Plasmodium falciparum histidine rich protein 2 and 3 (pfhrp2 and pfhrp3) gene deletions threatens their usefulness as malaria diagnostic and surveillance tools. The pfhrp2 and pfhrp3 gene deletions surveillance was conducted in P. falciparum parasite populations in Uganda. Methods Three-hundred (n = 300) P. falciparum isolates collected from cross-sectional malaria surveys in symptomatic individuals in 48 districts of eastern and western Uganda were analysed for the presence of pfhrp2 and pfhrp3 genes. Presence of parasite DNA was confirmed by PCR amplification of the 18s rRNA gene, msp1 and msp2 single copy genes. Presence or absence of deletions was confirmed by amplification of exon1 and exon2 of pfhrp2 and pfhrp3 using gene specific PCR. Results Overall, pfhrp2 and pfhrp3 gene deletions were detected in 29/300 (9.7%, 95% CI 6.6–13.6%) parasite isolates. The pfhrp2 gene was deleted in 10/300 (3.3%, 95% CI 1.6–6.0%) isolates, pfhrp3 in 9/300 (3.0%, 95% CI 1.4–5.6%) while both pfhrp2 and pfhrp3 were deleted in 10/300 (3.3%, 95% CI 1.6–6.0%) parasite isolates. Proportion of pfhrp2/3 deletions was higher in the eastern 14.7% (95% CI 9.7–20.0%) compared to the western region 3.1% (95% CI 0.8–7.7%), p = 0.001. Geographical location was associated with gene deletions aOR 6.25 (2.02–23.55), p = 0.003. Conclusions This is the first large-scale survey reporting the presence of pfhrp2/3 gene deletions in P. falciparum isolates in Uganda. Roll out of RDTs for malaria diagnosis should take into consideration the existence of pfhrp2/3 gene deletions particularly in areas where they were detected. Periodic pfhrp2/3 surveys are recommended to inform future decisions for deployment of alternative RDTs

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir

Communıty Partıcıpatıon And Sustaınabılıty Of Donor-Funded Agrıcultural Projects In Uganda ( The Case Of Potato Projects In Kabale Dıstrıct)

This study examined the effect of community involvement on the sustainability of donor-funded agricultural projects in Uganda, specifically the potato projects in Kabale District. The study used a mixed methods research technique using a cross-sectional survey design based on questionnaires, interviews and documentary review. Using basic random and purposeful selection methods, 196 respondents were chosen as a sample from a total of 400. Using descriptive statistical methods like mean and standard deviation, quantitative data were examined. The impact of community participation on sustainability of donor funded potato projects was determined using regression analysis. The findings indicated that, project design, (R Square =.180, P .01).  project resourcing (R Square = 925, P .01) and project monitoring and evaluation (R Square =.147**, P.01) affects sustainability of donor funded agricultural projects by roughly 90%. In conclusion, it has been established that, community participation has provided knowledge & information only to a limited extent that has not had any substantial impact on sustainability of donor funded potato projects. The study recommends that donors should all include potato project stakeholders in project design and implementation, project resourcing, and project monitoring and evaluation if potato projects are to be sustainable world overs globally, particularly in those involving potato projects

Strategic Planning and Business Sustainability of SMEs in Kigezi Sub-Region

This study looked at how strategic planning affected business sustainability of small and medium-sized businesses in Uganda. A Kigezi sub-regional case. Utilizing a correctional sectional study design, the investigation was conducted. The study's use of both quantitative and qualitative approaches allowed it to evaluate the relationship between the factors it was examining.  A sample of 105 respondents was selected using simple random selection and purposive sampling techniques. The quantitative and qualitative data from the respondents were analyzed using SPSS Version 23.0 and theme analysis, respectively. Tables providing quantitative results in the form of descriptive statistics, correlations, and regressions were presented based on the study's goals. The study found a significant association between strategic planning and the long-term viability of SMEs' businesses (r =.789, P.01). The research's findings and analyses indicate a strong relationship between strategic planning and SMEs' ability to remain competitive in the Kigezi sub-region. According to the study, the majority of respondents said that long-term success for SMEs was strongly impacted by strategic planning.  According to the study, SMEs should focus on strategic planning for business longevity if they want to successfully continue their businesses

The impact of internal controls on SACCO performance in Rukiga, Uganda

Purpose: The research on the internal controls of Rukiga SACCO was conducted in Rukiga District to examine the segregation of duties, determine the impact of independent checks, and assess the risk management on the financial performance of the organization. Research methodology: This research was carried out after the cross-sectional survey. The bivariate correlations between the predictor components and the dependent variable were examined using a Pearson correlation matrix, and a linear regression model was used to fit the data. Results: The regression model results showed that segregation of duties (R=762), independent checks (R=676), and risk management (R=899) had beneficial influence on Rukiga SACCO performance. Furthermore, the performance was impacted by risk management, separation of roles, and independent checks. Limitations: The structured questionnaire, which was administered by the participant, served as the primary data collection tool. The probability of non-responses occurred due to the loss of control over the questionnaire after submission to respondents. This situation had a significant impact on the data analysis and the generalizability of the findings. Contribution: Task segregation, independent auditing, and risk management should be considered to achieve loan portfolio expansion, profitability development, and market share increase, which were crucial elements of Rukiga SACCO performance

Factors associated with malaria parasitaemia among children under 5 years in Uganda: a secondary data analysis of the 2014 Malaria Indicator Survey dataset

Abstract Background In the midst of success with malaria reduction in Uganda, there are areas that still have high prevalence of malaria parasitaemia. This project aimed at investigating factors associated with this prevalence and its relationship with anaemia. Methods This is a secondary data analysis of the 2014 Malaria Indicator Survey dataset of children under 5 years. All had a blood sample taken by finger or heel prick for determination of malaria parasitaemia and estimation of haemoglobin level for anaemia status. The main outcome was the presence of malaria parasitaemia by microscopy and independent variables included: age, gender, residence (urban vs rural), use of a long-lasting, insecticidal-treated net, indoor residual spraying (IRS) of household in the past 6 months, mother’s highest education level, mother heard malaria prevention message in the past 6 months, and household wealth status. Results The analysis included 4930 children and of these, 938 (19.04%: 95% CI 16.63–21.71) tested positive for malaria parasites. Malaria parasite prevalence significantly increased from 11.08 (95% CI 9.12–13.40) among children with no anaemia to 50.99% (95% CI 39.13–62.74) with severe anaemia (Chi-square p-value = 0.001). Additionally, prevalence significantly rose from the youngest age group (under 6 months) by 1.62 times (95% CI 1.04–2.52, p = 0.033) among the age group of 7–12 months and to four times (95% CI 2.57–6.45, p = 0.001) among those who were between 49 and 59 months. The following were associated with reduced parasitaemia: IRS use (AOR 0.23 [0.08–0.61], p = 0.004), educated mothers (primary AOR 0.75 [0.59–0.96], p = 0.023 to tertiary AOR 0.11 [0.02–0.53], 0.006), mother heard malaria message (AOR 0.78 [0.62–0.99], p = 0.037), and wealthier households (richest AOR 0.17 [0.08–0.36], p = 0.001). Conclusions Increasing malaria parasite prevalence among children under 5 years is still related to increasing age and severity of anaemia even in the context of decreasing malaria prevalence. Designing interventions that include the use of IRS and behaviour change communication tailored to include older children, especially in areas with high malaria prevalence, could be of added value. All this should be done in an environment that improves the socio-economic status and equity of such populations