Community-based antiretroviral therapy versus standard clinic-based services for HIV in South Africa and Uganda (DO ART): a randomised trial

Background: Community-based delivery of antiretroviral therapy (ART) for HIV, including ART initiation, clinical and laboratory monitoring, and refills, could reduce barriers to treatment and improve viral suppression, reducing the gap in access to care for individuals who have detectable HIV viral load, including men who are less likely than women to be virally suppressed. We aimed to test the effect of community-based ART delivery on viral suppression among people living with HIV not on ART. / Methods: We did a household-randomised, unblinded trial (DO ART) of delivery of ART in the community compared with the clinic in rural and peri-urban settings in KwaZulu-Natal, South Africa and the Sheema District, Uganda. After community-based HIV testing, people living with HIV were randomly assigned (1:1:1) with mobile phone software to community-based ART initiation with quarterly monitoring and ART refills through mobile vans; ART initiation at the clinic followed by mobile van monitoring and refills (hybrid approach); or standard clinic ART initiation and refills. The primary outcome was HIV viral suppression at 12 months. If the difference in viral suppression was not superior between study groups, an a-priori test for non-inferiority was done to test for a relative risk (RR) of more than 0·95. The cost per person virally suppressed was a co-primary outcome of the study. This study is registered with ClinicalTrials.gov, NCT02929992. / Findings: Between May 26, 2016, and March 28, 2019, of 2479 assessed for eligibility, 1315 people living with HIV and not on ART with detectable viral load at baseline were randomly assigned; 666 (51%) were men. Retention at the month 12 visit was 95% (n=1253). At 12 months, community-based ART increased viral suppression compared with the clinic group (306 [74%] vs 269 [63%], RR 1·18, 95% CI 1·07–1·29; psuperiority=0·0005) and the hybrid approach was non-inferior (282 [68%] vs 269 [63%], RR 1·08, 0·98–1·19; pnon-inferiority=0·0049). Community-based ART increased viral suppression among men (73%, RR 1·34, 95% CI 1·16–1·55; psuperiority<0·0001) as did the hybrid approach (66%, RR 1·19, 1·02–1·40; psuperiority=0·026), compared with clinic-based ART (54%). Viral suppression was similar for men (n=156 [73%]) and women (n=150 [75%]) in the community-based ART group. With efficient scale-up, community-based ART could cost US$275–452 per person reaching viral suppression. Community-based ART was considered safe, with few adverse events. / Interpretation: In high and medium HIV prevalence settings in South Africa and Uganda, community-based delivery of ART significantly increased viral suppression compared with clinic-based ART, particularly among men, eliminating disparities in viral suppression by gender. Community-based ART should be implemented and evaluated in different contexts for people with detectable viral load. / Funding: The Bill & Melinda Gates Foundation; the University of Washington and Fred Hutch Center for AIDS Research; the Wellcome Trust; the University of Washington Royalty Research Fund; and the University of Washington King K Holmes Endowed Professorship in STDs and AIDS

Facilitating Knowledge Visualisation as Communication and Knowledge Transfer Mechanism in Postgraduate Learning

Advances in technology and subsequent access to inexpensive software have made visualisation, as a method of knowledge creation and transfer, more accessible. Visualisations have been used to support knowledge representation and transfer in teaching but the focus has primarily been on creating visualisations for learner consumption. The idea of students becoming active participants in producing visualisations, as part of knowledge creation and learning, has largely been overlooked. The study reported here investigated the use of visualisation for summarising knowledge at postgraduate level. The student’s need to assimilate and organise knowledge is an important part of their learning. We suggest that it would be useful for students to learn how to produce knowledge visualisations as part of this activity. The production is an act of knowledge creation, which can improve their comprehension of the research literature. Producing visualisations is not necessarily straightforward and it is therefore advisable to scaffold the process. We propose a faded-struts learning process that gradually removes scaffolding as the learner masters the principles and becomes more adept. The contribution of this research is to present the idea of providing worked examples and faded examples to support postgraduate learning. This helps postgraduates to craft knowledge visualisations so that they can slowly become more proficient and independent. Due to the ubiquity of mobile devices we propose providing this support on these devices, incorporating their unique constraints and affordances in our learning process. This is essentially a proof of concept paper, suggesting how the idea could be realised. Further work is necessary to test the idea with students and to extend the repertoire of mobile learning (m-learning) visualisation tasks.College of Engineering, Science and Technolog

In quest of a systematic framework for unifying and defining nanoscience

This article proposes a systematic framework for unifying and defining nanoscience based on historic first principles and step logic that led to a “central paradigm” (i.e., unifying framework) for traditional elemental/small-molecule chemistry. As such, a Nanomaterials classification roadmap is proposed, which divides all nanomatter into Category I: discrete, well-defined and Category II: statistical, undefined nanoparticles. We consider only Category I, well-defined nanoparticles which are >90% monodisperse as a function of Critical Nanoscale Design Parameters (CNDPs) defined according to: (a) size, (b) shape, (c) surface chemistry, (d) flexibility, and (e) elemental composition. Classified as either hard (H) (i.e., inorganic-based) or soft (S) (i.e., organic-based) categories, these nanoparticles were found to manifest pervasive atom mimicry features that included: (1) a dominance of zero-dimensional (0D) core–shell nanoarchitectures, (2) the ability to self-assemble or chemically bond as discrete, quantized nanounits, and (3) exhibited well-defined nanoscale valencies and stoichiometries reminiscent of atom-based elements. These discrete nanoparticle categories are referred to as hard or soft particle nanoelements. Many examples describing chemical bonding/assembly of these nanoelements have been reported in the literature. We refer to these hard:hard (H-n:H-n), soft:soft (S-n:S-n), or hard:soft (H-n:S-n) nanoelement combinations as nanocompounds. Due to their quantized features, many nanoelement and nanocompound categories are reported to exhibit well-defined nanoperiodic property patterns. These periodic property patterns are dependent on their quantized nanofeatures (CNDPs) and dramatically influence intrinsic physicochemical properties (i.e., melting points, reactivity/self-assembly, sterics, and nanoencapsulation), as well as important functional/performance properties (i.e., magnetic, photonic, electronic, and toxicologic properties). We propose this perspective as a modest first step toward more clearly defining synthetic nanochemistry as well as providing a systematic framework for unifying nanoscience. With further progress, one should anticipate the evolution of future nanoperiodic table(s) suitable for predicting important risk/benefit boundaries in the field of nanoscience

From May’s Laws to May’s legacy

The Institutions of Politics; Design, Workings, and implications ( do not use, ended 1-1-2020

Socs3b regulates the development and function of innate immune cells in zebrafish

Introduction: Suppressor of cytokine signaling 3 (SOCS3) is a critical component of the negative feedback regulation that controls signaling by cytokines and other factors thereby ensuring that important processes such as hematopoiesis and inflammation occur at appropriate levels. Methods: To gain further insights into SOCS3 function, the zebrafish socs3b gene was investigated through analysis of a knockout line generated using CRISPR/Cas9-mediated genome editing. Results: Zebrafish socs3b knockout embryos displayed elevated numbers of neutrophils during primitive and definitive hematopoiesis but macrophage numbers were not altered. However, the absence of socs3b reduced neutrophil functionality but enhanced macrophage responses. Adult socs3b knockout zebrafish displayed reduced survival that correlated with an eye pathology involving extensive infiltration of neutrophils and macrophages along with immune cell dysregulation in other tissues. Discussion: These findings identify a conserved role for Socs3b in the regulation of neutrophil production and macrophage activation

A retrial queueing system with a variable number of active servers:Dynamic manpower planning in a call center

A retrial queueing model is considered with Poisson input and an unlimited number of servers. At any epoch only a finite number of the servers are active, the others are called dormant. An active server is always in one of two possible states, idle or busy. When upon arrival of a customer at least one of the active servers is idle, the newly arrived customer goes into service immediately, making the idle server busy. When at an arrival epoch all active servers are busy, the decision must be made to send the newly arrived customer into orbit, or to activate a dormant server for immediate service of the arrived customer. Customers in orbit try to reenter the system after an exponentially distributed retrial time. At service completion epochs the decision must be made to keep the newly become idle server active, or to make this server dormant. The service times of the customers are independent and have a Coxian-2 distribution. Given specific costs for activating servers, keeping servers active and a holding cost for customers staying in orbit, the problem is when to activate and shut down servers in order to minimize the long-run average cost per unit time. Using Markov decision theory an efficient algorithm is discussed for calculating an optimal policy