Characterisation and Calibration of ZEPLIN III - A Dark Matter Detector

The ZEPLIN III liquid xenon dark matter detector is designed to potentially discover the WIMP - a supersymmetric galactic dark matter candidate. This thesis presents experimental results of the ZEPLIN III commissioning studies, in preparation for the first and second underground science runs. Data acquired on the surface, at the Imperial College London laboratories, were used to characterise the instrument’s response in terms of light yield (LY) and single photoelectron (SPE) spectra. A zero-field LY was measured as 7.42±0.37 phe/keV and 18.12±0.91 phe/keV in dedicated single- and dual-phase high yield configurations, respectively, consistent with Monte Carlo simulations. Mean SPE measured pulse areas ranged from 41.78±1.55 Vps to 52.37±1.59 Vps, depending on the method employed. A 3-D position reconstruction was verified and, significantly, no evidence of a potentially-contaminating background -population was observed. This study directly lead to critical development of the DAQ software and hardware configuration. The PMT array was confirmed as responsive and, crucially, the particle discrimination principle was demonstrated. Zero-field LYs of (4.6-4.7) ±0.5 phe/keV were recovered from the centre of the chamber, exceeding simulation predictions. With-field (3.01 kV/cm in the liquid) LYs of (1.2-1.8) ±0.3 phe/keV from the liquid scintillation (S1) and an electroluminescence yield (S2) of (98-140) ±35 phe/keV from the gas phase were also determined. ZEPLIN III was deployed in the Boulby Underground Laboratory, UK and demonstrated successful operation at high field (up to 3.79 kV/cm in the liquid), in situ. An alternative Poisson method for obtaining single photoelectron distributions was developed by the ZEPLIN collaboration. The origin of long- events in surface data was investigated and ultimately resolved as an artefact of early versions of the data reduction software. An S1 zero-field LY of 4.72±0.10 phe/keV, obtained with a 57Co external source, was recovered for the centre of the chamber. The instrument’s energy resolution was evaluated and a novel parameterisation approach, developed by the author, yielded sigma=1.08±0.06 p E(keV ) with a dominant stochastic term. A ‘flat-fielding’ method was established, proving to minimise the resolution significantly, yielding 8.6% and 7.3% for S1 and S2, respectively, in the fiducialised anti-correlated energy channel. This flat-fielding recipe, along with construction of the light collection correction matrices, formed the basis of the final procedures subsequently applied to first science run data-sets

Maternal HIV infection associated with small-for-gestational age infants but not preterm births: evidence from rural South Africa

BACKGROUND: Human immunodeficiency virus (HIV) is prevalent in many countries where small-for-gestational age (SGA) and premature delivery are also common. However, the associations between maternal HIV, preterm delivery and SGA infants remain unclear. We estimate the prevalence of SGA and preterm (<37 weeks) births, their associations with antenatal maternal HIV infection and their contribution to infant mortality, in a high HIV prevalent, rural area in South Africa.METHODS: Data were collected, in a non-randomized intervention cohort study, on all women attending antenatal clinics (2001-2004), before the availability of antiretroviral treatment. Newborns were weighed and gestational age was determined (based on last menstrual period plus midwife assessment antenatally). Poisson regression with robust variance assessed risk factors for preterm and SGA birth, while Cox regression assessed infant mortality and associated factors.RESULTS: Of 2368 live born singletons, 16.6% were SGA and 21.4% were preterm. HIV-infected women (n= 1189) more commonly had SGA infants than uninfected women (18.1 versus 15.1%; P = 0.051), but percentages preterm were similar (21.8 versus 20.9%; P = 0.621). After adjustment for water source, delivery place, parity and maternal height, the SGA risk in HIV-infected women was higher [adjusted relative risk (aRR) 1.28, 95% confidence interval (CI): 1.06-1.53], but the association between maternal HIV infection and preterm delivery remained weak and not significant (aRR: 1.07, 95% CI: 0.91-1.26). In multivariable analyses, mortality under 1 year of age was significantly higher in SGA and severely SGA than in appropriate-for-gestational-age infants [adjusted hazard ratio (aHR): 2.12, 95% CI: 1.18-3.81 and 2.77, 95% CI: 1.56-4.91], but no difference in infant mortality was observed between the preterm and term infants (aHR: 1.18 95% CI: 0.79-1.79 for 34-36 weeks and 1.31, 95% CI: 0.58-2.94 for <34 weeks).CONCLUSIONS: Maternal HIV infection increases the risk of SGA, but not preterm births, in this cohort

Fish Consumption Measured during Pregnancy and Risk of Cardiovascular Diseases Later in Life: An Observational Prospective Study

Previous studies have indicated a protective effect of long chain n-3 PUFAs against cardiovascular disease; however, the overall evidence remains uncertain, and there is a general lack of knowledge in the field of cardiovascular epidemiology in women. Therefore, the objective of this study was to explore the association between fish intake and cardiovascular disease among 7429 women from a prospective pregnancy cohort in Aarhus, Denmark, who were followed for 12–17 years. Exposure information derived from a questionnaire sent to the women in gestation week 16, and daily fish consumption was quantified based on assumptions of standard portion sizes and food tables. Information on admissions to hospital was obtained from the Danish National Patient Registry and diagnoses of hypertensive, cerebrovascular and ischaemic heart disease were used to define the outcome: cardiovascular disease. During the follow-up period 263 events of cardiovascular disease were identified. Overall, there was no association between cardiovascular disease and fish intake, confidence intervals for effect estimates in the different fish intake groups were wide, overlapped and for all but one they encompassed unity. Restricting the analysis to women who had reported the same fish intake in a questionnaire in gestation week 30 did not alter these findings. In conclusion, our data from a prospective cohort of relatively young and initially healthy women from Aarhus linked with information from registries could not substantiate a protective effect of fish intake against cardiovascular disease

Tuberculosis and HIV co-infection in children

HIV is the top and tuberculosis is the second leading cause of death from infectious disease worldwide, with an estimated 8.7 million incident cases of tuberculosis and 2.5 million new HIV infections annually. The World Health Organization estimates that HIV prevalence among children with tuberculosis, in countries with moderate to high prevalence, ranges from 10 to 60%. The mechanisms promoting susceptibility of people with HIV to tuberculosis disease are incompletely understood, being likely caused by multifactorial processes. Paediatric tuberculosis and HIV have overlapping clinical manifestations, which could lead to missed or late diagnosis. Although every effort should be made to obtain a microbiologically-confirmed diagnosis in children with tuberculosis, in reality this may only be achieved in a minority, reflecting their paucibacillary nature and the difficulties in obtain samples. Rapid polymerase chain reaction tests, such as Xpert MTB/RIF assay, are increasingly used in children. The use of less or non invasive methods of sample collection, such as naso-pharyngeal aspirates and stool samples for a polymerase chain reaction-based diagnostic test tests and mycobacterial cultures is promising technique in HIV negative and HIV positive children. Anti-tuberculosis treatment should be started immediately at diagnosis with a four drug regimen, irrespective of the disease severity. Moreover, tuberculosis disease in an HIV infected child is considered to be a clinical indication for initiation of antiretroviral treatment. The World Health Organization recommends starting antiretroviral treatment in children as soon as anti-tuberculosis treatment is tolerated and within 2- 8 weeks after initiating it. The treatment of choice depends on the child’s age and availability of age-appropriate formulations, and potential drug interactions and resistance. Treatment of multi-drug resistant tuberculosis in HIV-infected children follows same principles as for HIV uninfected children. There are conflicting results on effectiveness of isoniazid preventive therapy in reducing incidence of tuberculosis disease in children with HIV. CONCLUSION: Data on HIV/TB co-infection in children are still lacking. There are on-going large clinical trials on the prevention and treatment of TB/HIV infection in children that hopefully will help to guide an evidence-based clinical practice in both resource-rich and resource-limited settings

National Guidelines for the prevention of mother-to-child transmission of HIV across Europe - how do countries differ?

Objectives: The aim was to summarize national prevention of mother-to-child transmission (PMTCT) guidelines across Europe and to identify differences between these. Methods: A survey was conducted using a structured questionnaire sent to experts in 25 European countries from January to March 2012, requesting a copy of the national guidelines. Responses were received from 23 countries. Results: Twenty-two (96%) countries supported a policy to recommend antenatal HIV screening for all pregnant women (15: opt-out strategy; 8: opt-in strategy). For HIV-positive women in whom the only indication for antiretroviral therapy (ART) was PMTCT, the recommended gestational age for commencing ART varied from 12 to 28 weeks: initiation before 19 weeks gestation was recommended in guidelines from nine countries; in France, the UK and the Netherlands, there was a wide range, from 14 to 24 weeks, whereas the Swiss and Ukrainian guidelines recommended starting at 24-28 weeks and the German/Austrian and Lithuanian at 28 weeks. Six national guidelines recommended inclusion of Zidovudine in antenatal ART regimens, and seven (37%) allowed continuation of Efavirenz for women conceiving on this drug. According to nine guidelines, zidovudine should always be used intrapartum. Eighteen national guidelines stated that HIV-positive women on successful ART can have a vaginal delivery. Viral load thresholds for vaginal delivery were <1000 copies/ml in 5 countries, <400 copies/ml in 3 and <50 copies/ml in 11 countries. Conclusion: There are important differences across Europe in national PMTCT guidelines, with most variation seen where the evidence-base remains limited. Such differences should be considered when interpreting research and surveillance finding

Risk Behaviors and Reasons for not Getting Tested for HIV among Men Who Have Sex with Men: An Online Survey in Peru

Men who have sex with men (MSM) account for the greatest burden of the HIV epidemic in Peru. Given that MSM are frequent users of the Internet, understanding the risk behaviors and the reasons for not getting tested among MSM who surf the Internet may improve the tailoring of future online behavioral interventions.From October 2007 to April 2008, we conducted an online survey among users of seven Peruvian gay websites.We received 1,481 surveys, 1,301 of which were included in the analysis. The median age of the participants was 22.5 years (range 12-71), 67% were homosexual, and the remainder was bisexual. Of survey respondents, 49.4% had never been tested for HIV and only 11.3% were contacted in-person during the last year by peer health educators from the Peruvian Ministry of Health and NGOs. Additionally, 50.8% had unprotected anal or vaginal sex at last intercourse, and a significant percentage reported a condom broken (22.1%), slipped (16.4%) or sexual intercourse initiated without wearing a condom (39.1%). The most common reasons for not getting tested for HIV among high-risk MSM were "I fear the consequences of a positive test result" (n = 55, 34.4%), and "I don't know where I can get tested" (n = 50, 31.3%).A small percentage of Peruvian MSM who answered our online survey, were reached by traditional peer-based education programs. Given that among high-risk MSM, fear of a positive test result and lack of awareness of places where to get tested are the most important reasons for not taking an HIV test, Internet interventions aimed at motivating HIV testing should work to reduce fear of testing and increase awareness of places that offer free HIV testing services to MSM

Trends in antiretroviral use in pregnancy in the UK and Ireland, 2008–2018

Introduction: HIV treatment recommendations have evolved over time, reflecting both growing availability of new antiretrovirals and accumulating evidence on their safe and effective use. We analysed patterns of antiretroviral use among diagnosed pregnant women living with HIV delivering in the UK and Ireland between 2008 and 2018 using national surveillance data. Methods: All singleton pregnancies with known outcomes and known timing of antiretroviral initiation reported to the National Surveillance of HIV in Pregnancy and Childhood were included. Every individual instance of specific antiretroviral use was the unit of analysis in generating a snapshot of antiretroviral use overall and over calendar time. The final analysis was restricted to the 14 most frequently prescribed antiretrovirals. Results: There were 12 099 singleton pregnancies reported during 2008–2018 and a total of 38 214 individual uses of the 14 most commonly prescribed antiretrovirals, the majority of which were started before conception (70.9%). In 2008, 37.7% (482/1279) of pregnancies were conceived under treatment, reaching 80.9% (509/629) by 2018. Patterns of antiretroviral use have changed over time, particularly for third agents. Between 2008 and 2018 the most frequently used protease inhibitor shifted from lopinavir to darunavir, whereas use of integrase inhibitors increased steadily over time. Conclusions: These national surveillance data enable investigation of the ‘real-world’ use of antiretrovirals in pregnancy on a population level. Findings demonstrate mixed responsiveness of antiretroviral prescription to changes in pregnancy guideline recommendations and may also reflect changes in commissioning and in the characteristics of pregnant women living with HIV