Undergraduate studies

Oxidative stress in the RPE is widely accepted as a contributing factor to AMD. We have previously shown that ribozyme-mediated reduction in the antioxidant enzyme manganese superoxide dismutase (MnSOD) leads to some of the features of geographic atrophy in mice. To develop a mouse model independent of viral injection, we used a conditional knockout of the Sod2 gene in the RPE to elevate mitochondrial oxidative stress in that cell layer. Experimental mice in which exon 3 of Sod2 was flanked by loxP sites were also transgenic for PVMD2-rtTA and tetO-PhCMV cre, so that cre recombinase was expressed only in the RPE. Pups of this genotype (Sod2(flox/flox)VMD2cre) were induced to express cre recombinase by feeding doxycycline-laced chow to nursing dams. Controls included mice of this genotype not treated with doxycycline and doxycycline-treated Sod2(flox/flox) mice lacking the cre transgene. Expression of cre in the RPE was verified by immunohistochemistry, and deletion of Sod2 exon 3 in...

To examine variation in source of information about sexual matters by sociodemographic factors, and associations with sexual behaviours and outcomes. Cross-sectional probability sample survey. British general population. 3408 men and women, aged 17-24 years, interviewed from 2010-2012 for third National Survey of Sexual Attitudes and Lifestyles. Main source of information (school, a parent, other); age and circumstances of first heterosexual intercourse; unsafe sex and distress about sex in past year; experience of sexually transmitted infection (STI) diagnoses, non-volitional sex or abortion (women only) ever. Citing school was associated with younger age, higher educational level and having lived with both parents. Citing a parent was associated, in women, with lower educational level and having lived with one parent. Relative to other sources, citing school was associated with older age at first sex (adjusted HR 0.73 (95% CI 0.65 to 0.83) men, 0.73 (0.65 to 0.82) women), lower li...

To assess progress in meeting young people's sex education needs in Britain by examining the current situation and changes over the past 20 years in sources of information about sexual matters and unmet information needs. Cross-sectional probability sample surveys. British general population. 3869 men and women aged 16-24 years, interviewed 2010-2012 for the third National Survey of Sexual Attitudes & Lifestyles (Natsal-3), compared with 16-24 year-olds in Natsal-1 (1990-1991; 792 men and women) and Natsal-2 (1999-2001; 2673 men and women). Reported source of information about sexual matters, unmet information needs and preferred source of additional information. Between 1990 and 2012, the proportion citing school lessons as their main source of information about sexual matters increased from 28.2% (95% CI 24.6 to 32.1) to 40.3% (95% CI 38.6 to 42.1). In 2010-2012, parents were reported as a main source by only 7.1% (95% CI 5.8 to 8.7) of men and 14.1% (95% CI 12.6 to 15.7) of w...

Men who pay for sex (MPS) are considered a bridging population for sexually transmitted infections (STI). However, the extent, characteristics and role of MPS in transmission is poorly understood. We investigate these questions using data from Britain's third National Survey of Sexual Attitudes and Lifestyles (Natsal-3). We performed complex survey analyses of data from 6293 men aged 16-74 years resident in Britain who completed Natsal-3, a probability sample survey undertaken during 2010-2012, using computer-assisted personal interviewing and computer-assisted self-interview. 11.0% (95% CI10.1% to 11.9%) of all men reported ever paying for sex. Among MPS, 18.4% (95% CI 18.2% to 18.7%) of their lifetime sexual partners were paid. 3.6% (95% CI 3.1% to 4.2%) of men had paid for sex in the past 5 years. Partners of MPS constitute 14.7% of all reported partners and MPS report 15.6% of all reported STI diagnoses in the past 5 years. Paying for sex in the past 5 years was strongly ass...

Establishing the clinical significance of symptoms of sexual dysfunction is challenging. To address this, the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) introduced two new morbidity criteria (duration and symptom severity) to the existing criteria of distress. This study sought to establish the impact of these three criteria on the population prevalence of sexual function problems. The data come from a national probability survey (Natsal-3) and are based on 11,509 male and female participants aged 16-74, reporting at least one sexual partner in the past year. The key outcomes were: proportion of individuals reporting proxy measures of DSM-5 problems, and the proportion of those meeting morbidity criteria. We found that among sexually active men, the prevalence of reporting one or more of four specific sexual problems was 38.2%, but 4.2% after applying the three morbidity criteria; corresponding figures for women reporting one or more of three ...

Chronic graft-versus-host disease (cGVHD) is associated with inadequate reconstitution of tolerogenic CD4+CD25+FOXP3+ regulatory T cells (Treg). Previous phase 1 studies identified a low daily dose of interleukin-2 (IL-2) that was well tolerated and did not exacerbate alloimmunity in active cGVHD. Low-dose IL-2 therapy augmented Treg in-vivo and was associated with clinical improvement. In the current phase 2 study, 35 adult patients with steroid-refractory cGVHD received daily IL-2 (1x10(6)IU/m(2)/d) for 12 weeks. Median time from transplantation and cGVHD onset was 616 (range, 270-2145) and 317 days (range, 28-1880) respectively. Two patients withdrew and 5 required IL-2 dose-reductions due to side-effects. Twenty of 33 evaluable patients (61%) had clinical responses at multiple cGVHD sites including liver, skin, gastrointestinal tract, lung, and joint/muscle/fascia. Three patients (9%) had progressive cGVHD. Compared with pretreatment levels, Treg and NK-cell counts rose >5-fo...

In 2000, a 10-year Teenage Pregnancy Strategy was launched in England to reduce conceptions in women younger than 18 years and social exclusion in young parents. We used routinely collected data and data from Britain's National Surveys of Sexual Attitudes and Lifestyles (Natsal) to examine progress towards these goals. In this observational study, we used random-effects meta-regression to analyse the change in conception rates from 1994-98 to 2009-13 by top-tier local authorities in England, in relation to Teenage Pregnancy Strategy-related expenditure per head, socioeconomic deprivation, and region. Data from similar probability sample surveys: Natsal-1 (1990-91), Natsal-2 (1999-2001), and Natsal-3 (2010-12) were used to assess the prevalence of risk factors and their association with conception in women younger than 18 years in women aged 18-24 years; and the prevalence of participation in education, work, and training in young mothers. Conception rates in women younger than 1...