DTI-based tractographic analysis of white matter alterations in HIV infected children

Despite early combination antiretroviral therapy (cART) administration, children born with human immunodeficiency virus (HIV) continue to demonstrate neurodevelopmental abnormalities. Often, there is a link between structural and functional abnormalities. Previously, we found HIV-associated changes in white matter and functional networks in a cohort of 7-year-old HIV infected (HIV+) children who intiatied early cART compared to uninfected controls. To explore possible relationships between these alterations, we used tractography to identify HIV-related abnormalities within structural connections located in functional resting state networks. Within HIV+ children (n=61), we identified white matter (WM) tracts with lower mean fractional anisotropy (FA) and/or higher mean diffusivity (MD) located in several functional networks, including the somatosensory, auditory, salience, default mode network (DMN), motor and basal ganglia networks compared to uninfected controls (n=46). Among the uninfected controls, children born to HIV+ mothers (exposed uninfected, HEU) (n=19) showed WM alterations (higher FA) compared to HIV unexposed uninfected children (HUU) (n=27) within tracts in the posterior DMN, visual (occipital lobe and lingual gyrus), salience and motor networks. The observed WM alterations in HIV+ children point to demyelination/dysmyelination within six networks. Four of these networks – the basal ganglia, default mode, salience and somatosensory – were all found to have altered functional connectivity in a previous study; therefore, these results point to damage or developmental delay in white matter may be related to or responsible for the HIV-associated functional abnormalities. The observed WM alterations in the HEU children suggest that even exposure to HIV and/or antiretroviral therapy (ART) also has long-term effects on axonal integrity in the developing brain

How CIOs Engage Boards on Digitisation: The Case of Financial Services Companies in South Africa

Boards as custodians of companies have to understand and lead digital transformation. Chief Information Officers (CIOs) can assist with educating and advising the board on digital transformation, but how do CIOs engage boards on the matter? Digitisation is at the heart of the financial services companies. Accordingly, this dissertation focussed on companies in the financial services industry. The main research question for this dissertation is: how do CIOs of South African (SA) financial services companies engage boards on digitisation? A detailed literature review was conducted which suggested research questions on digitisation, the role of the board and the CIO’s, engagement between them, and performance. The interview schedule was based on the foregoing topics. The researcher adopted an interpretivist epistemological perspective to understand digitisation engagements from the perspectives of board members, non-IT executives, and CIOs. The researcher employed a qualitative research method to gain an in-depth understanding of the subject. Fifteen semi-structured interviews were conducted with board members, non-IT executives and CIOs from financial services companies. Six key themes emerged from the thematic analysis of the interviews, namely: digitisation, the board’s role, the CIO’s role, non-IT executives’ role, digitisation engagement, and value. It’s important to note that the non-IT executives’ role was an additional role that emerged from the thematic analysis, this role had not been discussed in the literature review. Non-IT executives owned strategy and owned digitisation initiatives. A new Chief Digital Officer (CDO) role also emerged from the thematic analysis as a sub-theme of the CIO’s role. The CDO’s mandate was to drive company-wide digitisation over and above the CIO’s role. Considering the six themes collectively, the three entities (boards, non-IT executives, & CIOs) have a key role to play pertaining to digitisation. The findings suggested that CIOs often engaged the board through board meetings, board committees, and ad-hoc engagements. CIOs often educated the board on digital technologies, digitisation opportunities and digitisation issues. Further, findings suggested that digitisation engagement influenced How CIOs Engage Boards on Digitisation: The Case of Financial Services Companies in South Africa - 2 - value (e.g. responding to digitisation opportunities & issues) rather than performance which was difficult to prove. The dissertation concludes with methodological, substantive and scientific reflections, and recommendations for practice and future research. The dissertation contributes to the growing body of knowledge on digitisation and demonstrates how the logic espoused in the Complex context of Snowden and Boone's (2007) Cynefin framework can be used to guide how CIOs and boards engage on digitisation

Affordable flow cytometry for enumeration of absolute CD4(+ )T-lymphocytes to identify subtype C HIV-1 infected adults requiring antiretroviral therapy (ART) and monitoring response to ART in a resource-limited setting

BACKGROUND: The World Health Organization (WHO)'s "3 × 5 program" has spurred efforts to place 3 million people on combination antiretroviral therapy (ART) for treatment of AIDS in resource-limited countries. Paradoxically, the cost of CD4(+ )T-lymphocyte count essential for decision-making to commence HIV positive adults on ART as well as for monitoring responses to ART remains unaffordable in most resource-limited countries. Thus, low-cost methods for enumerating CD4(+ )T-lymphocyte are urgently needed. OBJECTIVE: To evaluate Cyflow cytometry (Cyflow SL, Partec, Munster, Germany) for enumeration of absolute CD4(+ )T-lymphocyte in subtype C HIV-1 seropositive subjects using FACSCount (Becton and Dickinson, Immunocytometry Systems, San Jose, CA, USA) as the "predicate method". METHODS: A total of 150 HIV-1 seropositive subjects were included in the evaluation exercise. Fifty-eight specimens were collected from pregnant HIV-1 seropositive women (subtype C drug resistance study). Twenty-seven specimens were collected from women and their spouses with AIDS followed in a Duke ART study to assess the immunologic and virologic responses to generic ART, comprising Stavudine, Lamivudine and Nevirapine (Stalanev, Varichem Labs, Harare, Zimbabwe). Sixty-five specimens were collected from AIDS patients enrolled in an ongoing Kaposi Sarcoma (KS) study to investigate impact of ART on KS progression. Enumeration of CD4(+ )T-lymphocytes using FACSCount is routinely conducted for all the three studies. The Medical Research Council of Zimbabwe and Medicines Control Authority of Zimbabwe approved the studies. Whole blood was collected in EDTA vacutainer tubes and aliquoted into two tubes (200 μL in each). CD4(+ )T-lymphocyte counts were enumerated using a Cyflow counter, in the Department of Immunology and a FACSCount in the Department of Obstetrics and Gynaecology within 6 hours of phlebotomy following manufacturers' instructions. RESULTS: Using linear regression analysis, there was a very strong correlation (R = 0.991) between the overall CD4(+ )T-lymphocyte counts obtained by FACSCount and those obtained by Cyflow. When data analysis was stratified by study groups, there was a strong correlation between the FACSCount and Cyflow CD4(+ )T-lymphocyte counts from subjects in the three independent studies; Subtype C resistance (R(2 )= 0.987), Duke ART (R(2 )= 0.980) and KS (R(2 )= 0.994), Table 1. Using Bland-Altman plots, the overall, absolute CD4(+ )T lymphocytes obtained by the two methods were in excellent agreement (mean difference 1.21, 95% Confidence Interval {CI): -2.1 to 3.3). For the 0–250 CD4(+ )T-lymphocytes range, the CD4 counts obtained using FACSCount were also in good agreement with those obtained using Cyflow counter (mean difference = 2.6 cells/μL, 95% CI: -1.1 to 6.3). Similarly, in the 251–500 (mean difference 1.0, cells/μL, 95% CI: -3.7 to 5.6) and the 501–1200 (mean difference = 0.29 cells/μL, 95% CI: -8.1 to 8.7) CD4 T-lymphocytes range, good agreement was observed. CONCLUSION: The Cyflow counter is as accurate as the FACSCount in enumerating absolute CD4(+ )T-lymphocytes in the range 1–1200 cells/μL. Cyflow cytometry is relatively affordable, easy to use technology that is useful not only in identifying HIV seropositive individuals who require ART but also for monitoring immunologic responses to ART

Spun-Up Rotation-Powered Magnetized White Dwarfs in Close Binaries as Possible Gamma-ray Sources: Signatures of Pulsed Modulation from AE Aquarii and AR Scorpii in Fermi-LAT Data

In this paper, the possibility of periodic pulsar-like gamma-ray emission from the white dwarfs in AE Aquarii and AR Scorpii is investigated. We show that the white dwarf magnetospheres in AE Aquarii and AR Scorpii can possibly induce potentials to accelerate charged particles to energies in excess of one tera electronvolt (TeV) with associated gamma-ray emission through processes such as curvature radiation, inverse Compton, and hadronic processes such as neutral pion decay. We report here pulsed gamma-ray signatures at or close to the spin period of white dwarfs in both AE Aquarii and AR Scorpii in the Fermi-LAT dataset. This may indicate that both these white dwarfs possibly contain a particle accelerator that can produce relativistic electrons and ions and associated high energy radiation. The possibility of pair production is also investigated, which could provide a source for relativistic e± pairs in the magnetosphere. This could possibly be a driver for other forms of lepton-induced multi-wavelength pulsar-like emission from these two systems as well, for example, to explain the recently detected pulsed radio emission from AE Aquarii and R Scorpii in MeerKAT observations at the spin period of the white dwarf. The possibility of future detection of AE Aquarii and AR Scorpii with the Cherenkov Telescope Array (CTA) is also discussed. The future Vera Rubin Observatory will make a revolutionary contribution to time-domain astrophysics, which may lead to the discovery of thousands of new transient sources, possibly also many more close binaries with highly spun-up magnetized white dwarfs such as AE Aquarii and AR Scorpii for future investigation

Predicting SARS-CoV-2 Evolution Using Population-Scale Intra-Host Diversity Data Derived from Public SRA Data

VCF Files for Population Genomics: Scaling to Millions of Samples Codeatho

Interactions of HIV and antiretroviral therapy with neutrophils and platelets

Neutrophils are important components of the innate immune system that mediate pathogen defense by multiple processes including phagocytosis, release of proteolytic enzymes, production of reactive oxygen species, and neutrophil extracellular trap formation. Abnormalities of neutrophil count and function have been described in the setting of HIV infection, with the majority of antiretroviral agents (ARVs), excluding zidovudine, having been reported to correct neutropenia. Questions still remain, however, about their impact on neutrophil function, particularly the possibility of persistent neutrophil activation, which could predispose people living with HIV to chronic inflammatory disorders, even in the presence of virally-suppressive treatment. In this context, the effects of protease inhibitors and integrase strand transfer inhibitors, in particular, on neutrophil function remain poorly understood and deserve further study. Besides mediating hemostatic functions, platelets are increasingly recognized as critical role players in the immune response against infection. In the setting of HIV, these cells have been found to harbor the virus, even in the presence of antiretroviral therapy (ART) potentially promoting viral dissemination. While HIV-infected individuals often present with thrombocytopenia, they have also been reported to have increased platelet activation, as measured by an upregulation of expression of CD62P (P-selectin), CD40 ligand, glycoprotein IV, and RANTES. Despite ART-mediated viral suppression, HIV-infected individuals reportedly have sustained platelet activation and dysfunction. This, in turn, contributes to persistent immune activation and an inflammatory vascular environment, seemingly involving neutrophil-platelet-endothelium interactions that increase the risk for development of comorbidities such as cardiovascular disease (CVD) that has become the leading cause of morbidity and mortality in HIV-infected individuals on treatment, clearly underscoring the importance of unraveling the possible etiologic roles of ARVs. In this context, abacavir and ritonavir-boosted lopinavir and darunavir have all been linked to an increased risk of CVD. This narrative review is therefore focused primarily on the role of neutrophils and platelets in HIV transmission and disease, as well as on the effect of HIV and the most common ARVs on the numbers and functions of these cells, including neutrophil-platelet-endothelial interactions.http://www.frontiersin.org/Immunologyam2022Immunolog

Leukocyte selenium, zinc, and copper concentrations in preeclamptic and normotensive pregnant women

Preeclampsia is an important cause of maternal and perinatal mortality worldwide. The etiology of this relatively common medical complication of pregnancy, however, remains unknown. We studied the relationship between maternal leukocyte selenium, zinc, and copper concentrations and the risk of preeclampsia in a large hospital-based case-control study. One hundred seventy-one women with proteinuric pregnancy-induced hypertension (with or without seizures) comprised the case group. Controls were 184 normotensive pregnant women. Leukocytes were separated from blood samples collected during the patients' postpartum labor and delivery admission. Leukocyte concentrations for the three cations were measured by inductively coupled plasma-mass spectrometry (ICP-MS). Concentrations for each cation were reported as micrograms per gram of total protein. Women with preeclampsia had significantly higher median leukocyte selenium concentrations than normotensive controls (3.23 vs 2.80 mu g/g total protein, p < 0.0001). Median leukocyte zinc concentrations were 31% higher in preeclamptics as compared with controls (179.15 vs 136.44 mu g/g total protein, p < 0.0001). Although median leukocyte copper concentrations were slightly higher for cases than controls, this difference did not reach statistical significance (17.72 vs 17.00 mu g/g total protein, p = 0.468). There was evidence of a linear increase in risk of preeclampsia with increasing concentrations of selenium and zinc. The relative risk for preeclampsia was 3.38 (adjusted odds ratio [OR] = 3.38, 95% confidence interval [CI] = 1.53-7.54) among women in the highest quartile of the control selenium distribution compared with women in the lowest quartile. The corresponding relative risk and 95% CI for preeclampsia was 5.30 (2.45-11.44) for women in the highest quartile of the control zinc distribution compared with women in the lowest quartile. There was no clear pattern of a linear trend in risk with increasing concentration of leukocyte copper concentrations (adjusted for Linear trend in risk = 0.299). Our results are consistent with some previous reports. Prospective studies are needed to determine whether observed alterations in selenium and zinc concentrations precede preeclampsia or whether the differences may be attributed to preeclampsia-related alterations in maternal and fetal-placental trace metal metabolism

Estimates of the prevalence of male circumcision in sub-Saharan Africa from 2010-2023 -A systematic review and meta-analysis

Background Male circumcision (MC) is a key part of the package of interventions to prevent HIV, the biggest health challenge in sub-Saharan Africa. Objective To estimate the male circumcision prevalence and to evaluate the progress towards meeting WHO targets in sub-Saharan Africa during the period 2010-2023. Methods We carried out a systematic review and meta-analysis of studies published during the period 2010-2023. We searched PubMed, Scopus, Cochrane CENTRAL, Google Scholar, WHO and the Demographic and Health Survey for reports on MC prevalence in sub-Saharan Africa. MC prevalence was synthesized using inverse-variance heterogeneity models, heterogeneity using I2 statistics and publication bias using funnel plots. Results A total of 53 studies were included. The overall prevalence during the study period was 45.9% (95% CI 32.3-59.8), with a higher MC prevalence in Eastern (69.9%, 95%CI 49.9-86.8) compared to Southern African (33.3%, 95%CI 21.7-46.2). The overall prevalence was higher in urban (45.3%, 95%CI 27.7-63.4) compared to rural settings (42.6%, 95% 26.5-59.5). Male circumcision prevalence increased from 40.2% (95% CI 25.0-56.3) during 2010-2015 to 56.2% (95% CI 31.5-79.5) during 2016-2023. Three countries exceeded 80% MC coverage, namely, Ethiopia, Kenya and Tanzania. Conclusion Overall, the current MC prevalence is below 50%, with higher prevalence in Eastern African countries and substantially lower prevalence in Southern Africa. Most of the priority countries need to do more to scale up medical male circumcision programs.Scopu

Seroprevalence of hepatitis C virus infection among indigent urban pregnant women in Zimbabwe

No Abstract. Central African Journal of Medicine Vol. 46 (1) 2000: pp. 1-