The cascade of care for HIV-exposed infants in rural South Africa

Human Immunodeficiency Virus (HIV) in infants is not straightforward to diagnose, those born with HIV have high mortality, and those starting treatment at older ages have poorer outcomes, making the optimisation of care for HIV-exposed infants extremely important. The cascade of care is a tool used to describe the pathway from testing of HIV-exposed infants to successful treatment of those diagnosed with HIV, and, when used at a population-level, can identify gaps in healthcare systems and monitor improvements over time. This thesis used routinely collected data to assess the cascade for an estimated 17,570 HIV-exposed infants born between 2010 and 2016 in the Hlabisa health sub-district, KwaZulu-Natal, South Africa, a rural area where the antenatal HIV seroprevalence was 48% in 2016. The key cascade stages considered were the proportion of HIV-exposed infants who received an HIV polymerase chain reaction (PCR) test, the proportion of infants diagnosed with HIV who initiated antiretroviral therapy (ART), and the proportion of infants on ART who achieved viral suppression. A deterministic and probabilistic data linkage algorithm was developed to link, at an individual-level, data from demographic surveillance, PCR test data from the National Health Laboratory Service, and data from TIER.net, the national Department of Health ART surveillance system. Results suggest that by two years of age, 88% of HIV-exposed infants born in the sub-district had been tested, and of those diagnosed with HIV, 65% had initiated ART, of whom 53% were still on ART, of whom 68% were virally suppressed. Limitations to each of the sources of data used were described, which may have led to errors in the linkage and estimates of the cascade. Improvements to data collection systems are required, both for the quality and continuity of clinical care as well as for surveillance and research purposes

Characterization of Heparan Sulfate-Protein Interactions for Synthetic Heparin Design

Heparin is a widely prescribed anticoagulant that has been in clinical use for over 70 years. It is a natural product and a special form of heparan sulfate, a heterogeneous polysaccharide that is expressed as a proteoglycan on the surface of all animal tissues. In recent years, the development of a chemoenzymatic method to synthesize specific heparan sulfate polysaccharides and oligosaccharides has enabled studies of the structure-based interactions between negatively charged heparan sulfate and its protein binding partners. A synthetic version of heparin and its low-molecular-weight derivatives could have several advantages over the drugs that are currently available. First, a synthetic drug would evade the historically contaminated porcine intestine supply chain from which heparin is currently derived. In addition, the structure of the drug could be tailored for improved safety and efficacy and to meet the needs of different patient populations. In this dissertation, we sought to characterize structure-function relationships of heparan sulfate with several goals: to reduce binding to platelet factor 4, an initiating step in heparin-induced thrombocytopenia; to identify the structure required for binding to Stabilin receptors, which clear heparins via the liver rather than the kidneys; and to create a heparan sulfate structure that has optimum bioavailability and activity against factors of the coagulation cascade. Through biochemical, cell-based and in vivo assays, we determined that PF4 binding was decreased by Sulf-2 treatment and by limiting the oligosaccharide length, that a 3-O-sulfated 10-mer is required for robust Stabilin binding, that a 19-mer will confer anti-IIa activity and that oligosaccharides as short as a 6-mer are bioavailable through subcutaneous injection.Doctor of Philosoph

Temperature and Size Dependence of Photoluminescence in Lead Chalcogenide Quantum Dot Films

This work presents temperature-dependent photoluminescence spectra for nanocrystalline films, cast from PbS and PbSe quantum dots with diameters ranging from 0.6 nm to 9.2 nm (band gaps from 0.52 eV to 1.96 eV). Across all sizes and materials, two emission peaks are observed in the photoluminescence spectra. A low-energy peak dominates at low temperatures, and a high-energy peak dominates at high temperatures. No materials-dependent effects are noted, but the spectral behavior is a strong function of nanocrystal band gap. Intensity trends, the spacing of the two emission peaks, and the shift of peak emission energy with temperature are all affected by band gap changes. Results are suggestive of a scenario in which one emission peak is due to a fixed-energy trap state. The impact of air exposure on spectral behavior is also considered, and likely explains many previous inconsistencies between similar studies. High-temperature emission is strongly quenched by exposure to oxygen, with quenching effects beginning within seconds of exposure. Low-temperature emission is largely unaffected by short-term air exposure. These results are modeled with the introduction of a dark trap state whose concentration grows as air exposure increases

Radiofrequency denervation for chronic back pain: a systematic review and meta-analysis

Objectives: To assess the effectiveness of radiofrequency denervation (RD) of lumbosacral anatomical targets for the management of chronic back pain. Design: Systematic review and meta-analysis of randomised controlled trials (RCTs). Methods: A database search (Medline, Medline in Process, Embase, CINHAL and the Cochrane library) was conducted from January 2014 to April 2019 for placebo or no-treatment controlled trials of RD for the management of chronic back pain. Included trials were quality assessed using the Cochrane Risk-of-Bias Tool and the quality of outcomes assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Meta-analysis was conducted to calculate mean difference (MD) in post-treatment Pain Score. Results: Nineteen RCTs were included in the review. There appears to be short-term pain relief (1–3 months) provided by RD of the sacroiliac joint (five trials, MD −1.53, CI −2.62 to 0.45) and intervertebral discs (four trials, MD −0.98, CI −1.84 to 0.12), but the placebo effect is large and additional intervention effect size is small (6 months) is uncertain. Conclusions: RD of selected lumbosacral targets appears to have a small, short-term, positive effect for the management of patients with chronic back pain. However, the quality of evidence for the majority of outcomes is low or very low quality and there is still a degree of uncertainty, particularly around the duration of effect

Little Association between Intracranial Arterial Stenosis and Lacunar Stroke

Atheromatous middle cerebral artery (MCA) stenosis could cause lacunar stroke by occluding lenticulostriate artery origins, but atheroma is common, and previous studies lacked suitable controls. We aimed to determine if intracranial atheroma was more common in lacunar than in cortical ischaemic stroke. We recruited patients with lacunar stroke and controls with mild cortical stroke, confirmed the stroke subtype with magnetic resonance imaging and used transcranial Doppler ultrasound imaging to record flow velocity and focal stenoses in the basal intracranial arteries 1 month after stroke. We compared ipsi- and contralateral MCA mean flow velocities between stroke subtypes and tested for associations using linear mixed models. Amongst 67 lacunar and 67 mild cortical strokes, mean age 64 and 67 years, respectively, we found no difference in MCA mean flow velocity between cortical and lacunar patients. Increasing age and white matter lesion scores were independently associated with lower MCA flow velocities (0.2 cms−1 fall in velocity per year increase in age, p = 0.045; 3.75 cms−1 fall in flow velocity per point increase in white matter lesion score, p = 0.004). We found no intracranial arterial stenoses. MCA atheromatous stenosis is unlikely to be a common cause of lacunar stroke in white populations. Falling velocities with increasing white matter lesion scores may reflect progressive brain tissue loss leaving less tissue to supply

Co-producing Justice : International Social Economy Network Programme Report

While the significance of employment to desistance (giving up crime) is well established, there are multifarious obstacles to people with convictions accessing and sustaining work. Social enterprises are businesses that trade for a social purpose, rather than for the enrichment of shareholders or owners. It has been shown that social enterprise and cooperative structures of employment can circumnavigate some of the systemic obstacles to employment, such as criminal records and employer discrimination that people routinely encounter. Yet, one in six people in the UK have a criminal conviction; a large proportion of people are, therefore, affected by the impacts that contact with the justice system has on access to employment and, relatedly, opportunities to move on from offending. The House of Commons Work and Pensions Committee (2016) recognise that employment significantly reduces reoffending and can lead to other outcomes that can reduce reoffending (e.g. financial security and stable accommodation). The Scottish Government (2016) has recently co-produced, with the social enterprise sector, a ten-year Strategy to encourage the further development of the sector and contribute to an overarching ‘inclusive growth’ agenda, demonstrating considerable appetite for an evidence-informed approach for this demographic. Despite this, not only are such structures providing paid work a rarity in the UK justice system, the potential of social enterprises and co-operatives in this context has hardly been explored. Recent research (Roy et al., 2017; Weaver 2016; forthcoming) provides important evidence to suggest their potential to support desistance, recovery and integration; this project sought to build on this by exploring approaches to their implementation, connecting a range of multi-disciplinary international and local experts who can differently contribute towards their realisation. By combining these largely disconnected strands of research, siloed within specific disciplines, our aim has been to advance a more coherent interdisciplinary theorizing and exploration of the interactions, synergies and distinctions in these disciplinary fields and to influence the direction of future research, policy and practice in justice contexts

Geochemical Logging in the Cajon Pass Drill Hole and Its Application to a New, Oxide, Igneous Rock Classification Scheme

A new elemental oxide classification scheme for crystalline rocks is developed and applied to geochemical well logs from the Cajon Pass drill hole. This classification scheme takes advantage of measurements of elements taken by a geochemical logging tool string. It uses K_2O versus SiO_2/Al_2O_3 to distinguish between granites, granodiorites, tonalites, syenites, monzonites, diorites, and gabbros. Oxide measurements from cores are used to calibrate the elemental abundances determined from the well logs. From these logs, a detailed lithologic column of the core is generated. The lithologic column derived from the well log classification scheme is compared with a lithologic column constructed from core samples and well cuttings. In the upper 1295 m of the well, agreement between the two columns is good. Discrepancies occur from 1295 to 2073 m and are believed to be caused by the occurrence of rock types not distinguished by the classification scheme and/or the occurrence of secondary minerals. Despite these discrepancies, the well log-based classification scheme helps to distinguish changes in rock type and shows potential as an aid to the construction of lithologic columns in boreholes of crystalline rocks

Global Effect of COVID-19 on Small Businesses

COVID-19 is a worldwide pandemic that started in December 2019 in China. Smallbusinesses all over the world had no idea where to turn to, where their capital would go and whatto expect from a teeter-totter economy. With the help of government incentives and results fromsurveys such as the Small Business Pulse Survey as well as the Current Population Survey, Inthis study the following were concluded: 1) partaking in government incentives may better thebusiness, 2) having an online e-commerce presence may make or break the company, and 3)redesigning the business to work with the “new normal” may help define their niche and have athriving business

Experiences of transition to adult care and readiness to self-manage care in young people with perinatal HIV in England

Background: There are few data on young people’s own experiences of transferring from paediatric to adult care, or readiness to self-manage care. Methods: A total of 132 young people living with perinatal HIV, aged 14–25 years, answered questions about transition experiences. Results: Of the participants, 45 (34%), with a median age of 16 (interquartile range [IQR] 16–17), were in paediatric care, of whom 89% reported that transition discussions had begun, at median age 15 (IQR 14–16) years. Young people in adult care were more likely than those in paediatric care to self manage appointments (90% vs 42% respectively, P < 0.001), and know their antiretroviral therapy (ART) drugs (55% vs 37%, P = 0.033). Knowledge of most recent CD4 T cell count/VL was slightly better for those in adult care (48% vs 31%, P = 0.059); naming side effects of ART was similar (71% vs 60%, P = 0.119). Conclusions: Transition discussions occurred before movement from paediatric to adult care. Further education around ART, potential side effects, and CD4 T cell count/viral load knowledge is required

Readiness for Reform in Middle Schools Adopting PowerTeaching for Mathematics Instruction

Federal policy makers and school leaders increasingly recognize middle school math as a turning point in students’ academic success, especially in predicting high school graduation rates. New i3 scale-up grants allow large-scale implementation of proven reforms that increase student achievement. PowerTeaching (PT) is one such reform that centers on cooperative learning. A five year technologically-facilitated scale-up of PowerTeaching will bring the reform to 185 high-needs middle schools nationwide. In this pilot phase of the project, we will examine eight schools’ readiness for reform. Teacher questionnaires, interviews with school leaders, PT coaches and teachers, coaching feedback, and walk-through observation data will be used to determine school characteristics that impacted the initial implementation of the PT model and promote formative evaluation efforts