Liouville-space R-matrix-Floquet description of atomic radiative processes involving autoionizing states in the presence of intense electromagnetic fields

A reduced-density-operator description is developed for coherent optical phenomena in many-electron atomic systems, utilizing a Liouville-space, multiple-mode Floquet–Fourier representation. The Liouville-space formulation provides a natural generalization of the ordinary Hilbert-space (Hamiltonian) R-matrix-Floquet method, which has been developed for multi-photon transitions and laser-assisted electron–atom collision processes. In these applications, the R-matrix-Floquet method has been demonstrated to be capable of providing an accurate representation of the complex, multi-level structure of many-electron atomic systems in bound, continuum, and autoionizing states. The ordinary Hilbert-space (Hamiltonian) formulation of the R-matrix-Floquet method has been implemented in highly developed computer programs, which can provide a non-perturbative treatment of the interaction of a classical, multiple-mode electromagnetic field with a quantum system. This quantum system may correspond to a many-electron, bound atomic system and a single continuum electron. However, including pseudo-states in the expansion of the many-electron atomic wave function can provide a representation of multiple continuum electrons. The 'dressed' many-electron atomic states thereby obtained can be used in a realistic non-perturbative evaluation of the transition probabilities for an extensive class of atomic collision and radiation processes in the presence of intense electromagnetic fields. In order to incorporate environmental relaxation and decoherence phenomena, we propose to utilize the ordinary Hilbert-space (Hamiltonian) R-matrix-Floquet method as a starting-point for a Liouville-space (reduced-density-operator) formulation. To illustrate how the Liouville-space R-matrix-Floquet formulation can be implemented for coherent atomic radiative processes, we discuss applications to electromagnetically induced transparency, as well as to related pump–probe optical phenomena, and also to the unified description of radiative and dielectronic recombination in electron–ion beam interactions and high-temperature plasmas

Improving outcomes for adults living with HIV admitted to hospital in the era of high antiretroviral therapy coverage

Despite impressive successes with the public health approach in scaling up HIV testing and ART access in the past 20 years, advanced HIV disease remains a persistent problem. People living with HIV (PLHIV) who require admission to hospital are at extremely high risk of death. Tuberculosis (TB) remains the single biggest cause of HIV-related deaths. This thesis considers adults living with HIV admitted to hospital, with the major focus being a cluster randomised trial of enhanced TB diagnostics (CASTLE trial). The thesis consists of the following chapters: first, a systematic review of interventions to reduce mortality among adults living with HIV admitted to hospital in low- and middle-income countries. Ten studies were identified, including two TB diagnostics intervention trials that showed mortality reductions. Secondly, routine data from Queen Elizabeth Central Hospital in Blantyre, Malawi was used to estimate trends in incidence of adult HIV-related admission to hospital and in-hospital deaths. The population incidence of HIV related hospital admissions declined substantially all age and sex groups from 2012 to 2019. In-hospital case fatality for admitted PLHIV remained unchanged, at 23.5%, with no significant reduction in any age-sex group, and no association with ART use at admission. Thirdly, a cluster-randomised trial (Computer Aided Screening for Tuberculosis in Low Resource Environments: CASTLE) using admission day as the unit of randomisation was designed and conducted. Admission days were randomly assigned to: 1) enhanced diagnostics for TB using urine lipoarabinomannan (LAM) (SILVAMP-LAM, Fujicorp, Japan and LF-LAM, Alere/Abbot, USA), digital chest X-ray with computer aided diagnosis (dCXR-CAD) using CAD4TBv6 (Delft, Netherlands) plus usual care; or 2) to usual care alone. The primary outcome was TB treatment initiation during admission. Between 2 September 2020 and 15 February 2022, 415 adults were recruited during 207 admission-days. TB treatment was initiated in 46/208 (22%) in the enhanced TB diagnostics arm and 24/207 (12%) in the usual care arm (risk ratio [RR] 1.92, 95% CI 1.20-3.08). Urine SILVAMP-LAM/LF-LAM plus dCXR-CAD diagnostics identified more hospitalised PLHIV with TB than usual care, but with no evidence of impact on survival, undiagnosed TB, or TB treatment initiation within 24 hours. Unanticipated findings in CASTLE included poor concordance between SILVAMP-LAM and LF-LAM results. The PhD highlights the ongoing high mortality of people living with HIV in hospital, the relative paucity of evidence based interventions for this population, and the persistently high death rate. I show that an enhanced TB diagnostic intervention is feasible and increases the number of people diagnosed with TB. To achieve goals to get to zero AIDS deaths, people with advanced HIV disease particularly those in hospital, deserve greater research attention

Before the whistle blows: developing new paradigms in tuberculosis screening to maximise benefit and minimise harm [version 1; peer review: awaiting peer review]

We summarise recent emerging evidence around tuberculosis (TB) transmission and its role in tuberculosis epidemiology, and in novel TB screening and diagnostic tests that will likely become available in low-resource settings in the near future. Little consideration has been paid to how these novel new tests will be implemented, nor what the consequences for individuals, communities and health systems will be. In particular, because of low specificity and consequent false-positive diagnoses, and the low percentage of people who “screen positive” that will go onto develop active pulmonary disease, there is significant potential for inappropriate initiation of TB treatment, as well as stigmatisation, loss of livelihoods and in some setting institutionalisation, with uncertain benefit for individual health or community transmission. We use analogy to prompt consideration of how and where new TB screening tests could be implemented in TB screening programmes in low-resource settings. Acceptance and confidence in TB screening programmes depends on well-functioning public health programmes that use screening algorithms that minimise harms and balance population benefits with autonomy and respect for individuals. Before new TB screening tests and algorithms are introduced, more evidence for their effectiveness, costs, benefits and harms under real-world conditions are required

Towards Many-objective Optimisation with Hyper-heuristics: Identifying Good Heuristics with Indicators

PPSN 2016: 14th International Conference on Parallel Problem Solving from Nature, 17-21 September 2016, Edinburgh, ScotlandThis is the author accepted manuscript. The final version is available from Springer Verlag via the DOI in this record.The use of hyper-heuristics is increasing in the multi-objective optimisation domain, and the next logical advance in such methods is to use them in the solution of many-objective problems. Such problems comprise four or more objectives and are known to present a significant challenge to standard dominance-based evolutionary algorithms. We in- corporate three comparison operators as alternatives to dominance and investigate their potential to optimise many-objective problems with a hyper-heuristic from the literature. We discover that the best results are obtained using either the favour relation or hypervolume, but conclude that changing the comparison operator alone will not allow for the generation of estimated Pareto fronts that are both close to and fully cover the true Pareto front.This work was funded under EPSRC grant EP/K000519/1

Same-day antiretroviral therapy initiation in people living with HIV who have tuberculosis symptoms: a systematic review

Objectives Tuberculosis symptoms are very common among people living with HIV (PLHIV) initiating antiretroviral therapy (ART), are not specific for tuberculosis disease and may result in delayed ART start. The risks and benefits of same-day ART initiation in PLHIV with tuberculosis symptoms are unknown. Methods We systematically reviewed nine databases on 12 March 2020 to identify studies that investigated same-day ART initiation among PLHIV with tuberculosis symptoms and reported both their approach to TB screening and clinical outcomes. We extracted and summarised data about TB screening, numbers of people starting same-day ART and outcomes. Results We included four studies. Two studies deferred ART for everyone with any tuberculosis symptoms (one or more of cough, fever, night sweats or weight loss) and substantial numbers of people had deferred ART start (28% and 39% did not start same-day ART). Two studies permitted some people with tuberculosis symptoms to start same-day ART, and fewer people deferred ART (2% and 16% did not start same-day). Two of the four studies were conducted sequentially; proven viral load suppression at eight months was 31% when everyone with tuberculosis symptoms had ART deferred, and 44% when algorithm was changed so that some people with tuberculosis symptoms could start same-day ART. Conclusions Although tuberculosissymptoms are very common in people starting ART, there is insufficient evidence about whether presence of tuberculosis symptoms should lead to ART start being deferred or not. Research to inform clear guidelines would help maximise benefits of sameday ART

Increasing the accessibility and impact of justice-related student and practitioner research

Much good quality research by pre-doctoral students and case-work focused practitioners remains unpublished. However, their findings could contribute to the evidence base underpinning science and practice within international justice system contexts. There are two main challenges to making findings accessible: reaching all criminal justice stakeholders, and encouraging collaborative efforts in research addressing ‘real world’ problems. This article presents the rationale for a new, open access repository. The aim is to share good quality pre-doctoral and practitioner criminal justice research across traditional disciplinary and international borders. Such a repository should be easy to use, well maintained and sustainable. Its reach, value and impact also need to be measurable. We present the major considerations relating to the operation and workflow of such a repository, and outline the potential value, benefits and limitations. Our research suggests that the proposed repository could foster interdisciplinary and collaborative work to benefit global justice systems and societies

What is the optimum time to start antiretroviral therapy in people with HIV and tuberculosis coinfection? A systematic review and meta-analysis

Background: HIV and tuberculosis are frequently diagnosed concurrently. In March 2021, World Health Organization recommended that antiretroviral therapy (ART) should be started within two weeks of tuberculosis treatment start, at any CD4 count. We aimed to assess whether earlier ART improved outcomes in people with newly diagnosed HIV and tuberculosis. Methods: We did a systematic review by searching nine database for for trials that compared earlier ART to later ART initiation in people with HIV and tuberculosis. We included studied published from database inception to 12 March 2021. We compared ART within four weeks vs. ART more than four weeks after TB treatment, and ART within two weeks vs. ART between two and eight weeks, and stratified analysis by CD4 count. The main outcome was death; secondary outcomes included IRIS and AIDS-defining events. We used random effects meta-analysis to pool effect estimates. Results: 2468 abstracts were screened, from which we identified nine trials. Among people with all CD4 counts, there was no difference in mortality by earlier ART (≤ 4 week) vs. later ART (> 4 week) (risk difference [RD] 0%; 95% confidence interval [CI] -2% to +1%). Among people with CD4 count ≤50 cells/mm3, earlier ART (≤4 weeks) reduced risk of death (RD -6%; -10% to -1%). Among people with all CD4 counts earlier ART (≤4 weeks) increased the risk of IRIS (RD +6%, 95% CI +2% to +10%) and reduced the incidence of AIDS defining events (RD -2%, 95% CI -4% to 0%). Results were similar when trials were restricted to the five trials which permitted comparison of ART within two weeks to ART between two and eight weeks. Discussion: Earlier ART did not alter risk of death overall among people living with HIV who had TB disease. Trials were conducted between 2004 and 2014, before recommendations to treat HIV at any CD4 count or to rapidly start ART in people without TB. No trials included children or pregnant women. No trials included integrase inhibitors in ART regimens. For logistical and patient preference reasons, earlier ART initiation for everyone with TB and HIV may be preferred to later ART

Muscle Glycogen Utilisation during an Australian Rules Football Game.

PURPOSE: To better understand the carbohydrate (CHO) requirement of Australian Football (AF) match play by quantifying muscle glycogen utilisation during an in-season AF match. METHODS: After a 24 h CHO loading protocol of 8 g/kg and 2 g/kg in the pre-match meal, two elite male forward players had biopsies sampled from m. vastus lateralis before and after participation in a South Australian Football League game. Player A (87.2kg) consumed water only during match play whereas player B (87.6kg) consumed 88 g CHO via CHO gels. External load was quantified using global positioning system technology. RESULTS: Player A completed more minutes on the ground (115 vs. 98 min) and covered greater total distance (12.2 vs. 11.2 km) than Player B, though with similar high-speed running (837 vs. 1070 m) and sprinting (135 vs. 138 m), respectively. Muscle glycogen decreased by 66% in Player A (Pre-: 656, Post-: 223 mmol∙kg-1 dw) and 24% in Player B (Pre-: 544, Post-: 416 mmol∙kg-1 dw), respectively. CONCLUSION: Pre-match CHO loading elevated muscle glycogen concentrations (i.e. >500 mmol.kg-1 dw), the magnitude of which appears sufficient to meet the metabolic demands of elite AF match play. The glycogen cost of AF match play may be greater than soccer and rugby and CHO feeding may also spare muscle glycogen use. Further studies using larger sample sizes are now required to quantify the inter-individual variability of glycogen cost of match play (including muscle and fibre-type specific responses) as well examine potential metabolic and ergogenic effects of CHO feeding

Increasing confidence and changing behaviors in primary care providers engaged in genetic counselling.

BackgroundScreening and counseling for genetic conditions is an increasingly important part of primary care practice, particularly given the paucity of genetic counselors in the United States. However, primary care physicians (PCPs) often have an inadequate understanding of evidence-based screening; communication approaches that encourage shared decision-making; ethical, legal, and social implication (ELSI) issues related to screening for genetic mutations; and the basics of clinical genetics. This study explored whether an interactive, web-based genetics curriculum directed at PCPs in non-academic primary care settings was superior at changing practice knowledge, attitudes, and behaviors when compared to a traditional educational approach, particularly when discussing common genetic conditions.MethodsOne hundred twenty one PCPs in California and Pennsylvania physician practices were randomized to either an Intervention Group (IG) or Control Group (CG). IG physicians completed a 6 h interactive web-based curriculum covering communication skills, basics of genetic testing, risk assessment, ELSI issues and practice behaviors. CG physicians were provided with a traditional approach to Continuing Medical Education (CME) (clinical review articles) offering equivalent information.ResultsPCPs in the Intervention Group showed greater increases in knowledge compared to the Control Group. Intervention PCPs were also more satisfied with the educational materials, and more confident in their genetics knowledge and skills compared to those receiving traditional CME materials. Intervention PCPs felt that the web-based curriculum covered medical management, genetics, and ELSI issues significantly better than did the Control Group, and in comparison with traditional curricula. The Intervention Group felt the online tools offered several advantages, and engaged in better shared decision making with standardized patients, however, there was no difference in behavior change between groups with regard to increases in ELSI discussions between PCPs and patients.ConclusionWhile our intervention was deemed more enjoyable, demonstrated significant factual learning and retention, and increased shared decision making practices, there were few differences in behavior changes around ELSI discussions. Unfortunately, barriers to implementing behavior change in clinical genetics is not unique to our intervention. Perhaps the missing element is that busy physicians need systems-level support to engage in meaningful discussions around genetics issues. The next step in promoting active engagement between doctors and patients may be to put into place the tools needed for PCPs to easily access the materials they need at the point-of-care to engage in joint discussions around clinical genetics