Global identification of androgen response elements

Chromatin immunoprecipitation (ChIP) is an invaluable tool in the study of transcriptional regulation. ChIP methods require both a priori knowledge of the transcriptional regulators which are important for a given biological system and high-quality specific antibodies for these targets. The androgen receptor (AR) is known to play essential roles in male sexual development, in prostate cancer and in the function of many other AR-expressing cell types (e.g. neurons and myocytes). As a ligand-activated transcription factor the AR also represents an endogenous, inducible system to study transcriptional biology. Therefore, ChIP studies of the AR can make use of treatment contrast experiments to define its transcriptional targets. To date several studies have mapped AR binding sites using ChIP in combination with genome tiling microarrays (ChIP-chip) or direct sequencing (ChIP-seq), mainly in prostate cancer cell lines and with varying degrees of genomic coverage. These studies have provided new insights into the DNA sequences to which the AR can bind, identified AR cooperating transcription factors, mapped thousands of potential AR regulated genes and provided insights into the biological processes regulated by the AR. However, further ChIP studies will be required to fully characterise the dynamics of the AR-regulated transcriptional programme, to map the occupancy of different AR transcriptional complexes which result in different transcriptional output and to delineate the transcriptional networks downstream of the AR.

Sexual dimorphism in amphipods: the role of male posterior gnathopods revealed in Gammarus pulex

In the mate-guarding amphipod, Gammarus pulex, the enlarged male posterior gnathopods have been variously suggested to function to grasp and subdue the female, to be used as weapons in fights between males, to signal to the female the male presence and stimulate moult accelaration, egg development or egg extrusion. These hypotheses were tested in a series of experiments, the results of which reveal an unexpected function. Ablation of the posterior gnathopods of males showed that they were neither necessary for, nor advantageous in, establishment and/ or maintenance of precopula mate guarding, with or without competition with intact males. Furthermore, these appendages do not function to advance female moult, or stimulate egg development or extrusion. However, only males with intact posterior gnathopods were able to copulate. We also show that females require a full copulation of several bouts to extrude eggs. We conclude that the function of the posterior gnathopods is to facilitate copulation and suggest future studies focus on the selective pressures acting on copulating males.

Sex, drugs and STDs: Preliminary findings from the Belfast Youth Development Study

Young people's participation in sexual risk behaviours is commonly linked with participation in a range of other risky behaviours, and in particular with substance use behaviours. This cross-sectional analysis of the sixth sweep of the Belfast Youth Development Study aimed to examine associations between substance use and sexual activity and related risks among 17-19-year olds in Northern Ireland. Being sexual activity and participating in sexual risk behaviours was associated with the use of a range of licit and illicit substances particularly alcohol and ecstasy. Additionally, females were more likely to have been tested for a sexually transmitted disease (STD). The findings add to the existing research body suggesting that substance misuse and sexual risk behaviours tend to co-occur in adolescence and highlight a need to develop appropriate interventions and initiatives for school aged young people.

Dealing with a problem that doesn't exist?:Professional responses to female perpetrated child sexual abuse

Female involvement in sexual offences against children is more common than is generally thought and has serious implications for the long-term emotional and psychological well-being of victims. Drawing on findings from: a comprehensive review of the literature; an overview of relevant literature and legislation; and an electronic survey of Multi-Agency Public Protection Panels; this paper explores the criminal justice response to female sex offending in England, Wales and Northern Ireland. The literature highlights that the way in which professionals identify and respond to child sexual abuse has been shown to be influenced by the gender of the perpetrator. Equally, whilst similar to male sex offending in terms of the intrusiveness and seriousness of the abuse, some aspects of female sex offending can cause particular problems for professionals. The fact that some sexual abuse can be disguised as childcare can make it difficult for professionals to identify this type of abuse whilst high rates of co-offending bring additional difficulties in determining the degree of female involvement and assigning responsibility. The survey findings indicate that risk assessment tools for female sex offenders is a key area requiring development and point towards small inconsistencies in the current practice of risk assessing females in the community. The survey also identifies the lack of treatment programmes for this group of offenders as well as drawing attention to the need for national policies and procedures, staff training and the identification of areas of good practice. Increased discussion and debate about how best to work with this group of sex offenders is also required. Copyright © 2007 John Wiley & Sons, Ltd.

Pre-clinical development of a combination microbicide vaginal ring containing dapivirine and darunavir

Objectives: Combination microbicide vaginal rings may be more effective than single microbicide rings at reducing/preventing sexual transmission of HIV. Here, we report the preclinical development and macaque pharmacokinetics of matrix-type silicone elastomer vaginal rings containing dapivirine and darunavir.

Methods: Macaque rings containing 25 mg dapivirine, 300 mg darunavir and 100 mg dapivirine, and 300 mg darunavir were manufactured and characterised by differential scanning calorimetry. In vitro release was assessed into isopropanol/water and simulated vaginal fluid. Macaque vaginal fluid and blood serum concentrations for both antiretrovirals were measured during 28-day ring use. Tissue levels were measured on day 28. Ex vivo challenge studies were performed on vaginal fluid samples and IC50 values calculated.

Results: Darunavir caused a concentration-dependent reduction in the dapivirine melting temperature in both solid drug mixes and in the combination ring. In vitro release from rings was dependent on drug loading, the number of drugs present, and the release medium. In macaques, serum concentrations of both microbicides were maintained between 101–102 pg/mL. Vaginal fluid levels ranged between 103–104 ng/g and 104–105 ng/g for dapivirine and darunavir, respectively. Tissue concentrations ranges for each drug were: vagina (1.8×103–3.8×103 ng/g) > cervix (9.4×101–3.9×102 ng/g) > uterus (0–108 ng/g) > rectum (0–40 ng/g). Measured IC50 values were > 2 ng/mL for both compounds.

Conclusions: Based on these results, and in light of recent clinical progress of the 25mg dapivirine ring, a combination vaginal ring containing dapivirine and darunavir is a viable second-generation HIV microbicide candidate.

Provision for young people who have displayed harmful sexual behaviour

Over the past few decades, children and young people who have sexually harmed others have attracted increasing attention from researchers and policy makers. Although it is known that they form a small, but significant group, there are difficulties in gaining a clear indication of incidence since much of the existing research has involved small and heterogeneous samples, many of which were not UK-based and lack of control groups for comparison. Furthermore, many incidents of sexual abuse are likely to go unreported. The nature, extent and significant negative consequences of harmful sexual behaviour for the victims and perpetrators, make this an important issue for policy development and research investigation. Overall, research and knowledge in this important area are still accumulating and much remains to be confirmed. Although recent decades have seen a movement towards greater understanding of the issue of harmful sex behaviour, a gap remains. The purpose of the project was to help address this gap in knowledge.

Impact of abuse and neglect on the health and wellbeing of children:Child sexual abuse

During the past 30 years, the focus on the extent and nature of child abuse and neglect has been coupled with an increasing interest in the impact on children’s development, health and mental wellbeing. Child maltreatment is both a human rights violation and a complex public health issue, likely caused by a myriad of factors that involve the individual, the family, and the community. Child abuse includes any type of maltreatment or harm inflicted upon children and young people in interactions between adults (or older adolescents). Such maltreatment is likely to cause enduring harm to the child.
The different forms of abuse and neglect often occur together in one family and can affect one or more children. These include, in deceasing level of frequency: neglect; physical abuse and non-accidental injury; emotional abuse; and sexual abuse (Cawson et al, 2000; 2002). Recently, bullying and domestic violence have been included as forms of abuse of children.
There is a sizeable body of literature on the relationship between types of child maltreatment and a variety of negative health and mental health consequences. These include biological, psychological, and social deficits (for reviews, see Crittenden, 1998; Kendall-Tackett, 2001; 2003). Aside from the serious physical and health consequences of child maltreatment, several emotional and behavioural consequences for children have been noted in the literature.

Risk, Regulation and the Reintegration of Sexual Offenders

Media reporting of and public concern about sexual offending, particularly relating to children, affects and reflects political, policy and organisational responses to those convicted of such crimes. The development of regulatory policies on sexual offending has taken place within a highly emotive and overtly politicized public and policy discourse. This chapter charts the various ways in which the risks imagined or posed by sexual offenders have been conceptualised within public discourses and regulated and managed under the legislative and organisational ‘risk paradigm.’ Ultimately, it argues that risk-based responses to sexual offending are at best uncertain in their effects and at worst counterproductive, in that they often reduce the potential for successful reintegration. In seeking to look ‘beyond risk’, the chapter also explores the usefulness of restorative and related practices in supporting sex offender reintegration aimed at the primary and secondary levels of harm prevention.

Evaluation of a partnership between primary and secondary care providing an accessible Level 1 sexual health service in the community

Comprehensive testing for asymptomatic sexually transmitted infections in Northern Ireland has traditionally been provided by genitourinary medicine clinics. As patient demand for services has increased while budgets have remained limited, there has been increasing difficulty in accommodating this demand. In May 2013, the newly commissioned specialist Sexual Health service in the South Eastern Trust sought to pilot a new model of care working alongside a GP partnership of 12 practices. A training programme to enable GPs and practice nurses to deliver Level 1 sexual health care to heterosexual patients aged >16 years, in accordance with the standards of BASHH, was developed. A comprehensive care pathway and dedicated community health advisor supported this new model with close liaison between primary and secondary care. Testing for Chlamydia, gonorrhoea, HIV and syphilis was offered. The aims of the pilot were achieved, namely to provide accessible, cost-effective sexual health care within a framework of robust clinical governance. Furthermore, it uncovered a high positivity rate for Chlamydia, especially in young men attending their general practice, and demonstrated a high level of patient satisfaction. Moreover the capacity of secondary care to deliver Levels 2 and 3 services was increased.

Gaining ethical approvals to undertake sexual health research with young people in the UK: Applying a 'Children's Rights Based Approach'

This paper (co-written with Dr Maria Lohan, Dr Carmel Kelly & Professor Laura Lundy) will describe the ethical review process to undertake health research in the UK, and explain an approach that can help researchers deal with ethical and methodological dilemmas in their research. Ethical review is necessary to ensure researchers and participants are protected, yet the requirement to ‘pass’ numerous committees may be challenging particularly for health researchers who work with vulnerable groups and sensitive topics. The inclusion of these groups/topics is crucial if health researchers are to understand health disparities and implement appropriate interventions with health benefits for vulnerable populations. It is proposed that to overcome ethical and methodological challenges and pitfalls, researchers must implement strategies that advocate for, and increase the participation of, vulnerable populations in health research. A ‘children’s rights based approach’ using participatory methodology will be described that draws on the jurisprudence of international law, (United Nations Convention on the Rights of the Child, 1989) and provides a framework that may empower ethics committees to carry out their function confidently. The role of the researcher, framed within the context of doctoral level study, will be reviewed in terms of the investment required and benefits of utilising this approach. It will be argued that adopting this approach with vulnerable groups, not only guarantees their meaningful participation in the research process and permits their voices to be heard, but also offers ethics committees an internationally agreed upon legal framework, ratified by their governing States, from which to fulfil their obligations and resolve their ethical dilemmas. Increasing the representation and participation of vulnerable groups in health research can inform the development of health policy and practice based on ‘insider knowledge’ that better engages with and more adequately reflects their specific needs. This is likely to yield numerous health, social and economic benefits for all of society through the delivery of more equitable, effective and sustainable services.

Microbicide Vaginal Rings: Technological Challenges and Clinical Development

Vaginal rings (VRs) are flexible, torus-shaped, polymeric devices designed to sustain delivery of pharmaceutical drugs to the vagina for clinical benefit. Following first report in a 1970 patent application, several steroid-releasing VR products have since been marketed for use in hormone replacement therapy and contraception. Since 2002, there has been growing interest in the use of VR technology for delivery of drugs that can reduce the risk of sexual acquisition of human immunodeficiency virus type 1 (HIV-1), the causative agent of acquired immunodeficiency syndrome (AIDS). Although no vaginally-administered product has yet been approved for HIV reduction/prevention, extensive research efforts are continuing and a number of VR devices offering sustained release of so-called ‘HIV microbicide’ compounds are currently being evaluated in late-stage clinical studies. This review article provides an overview of the published scientific literature within this important field of research, focusing primarily on articles published within peer-reviewed journal publications. Many important aspects of microbicide-releasing VR technology are discussed, with a particular emphasis on the technological, manufacturing and clinical challenges that have emerged in recent years.

Ethics in sexual behavior assessment and support for people with intellectual disability

Sexuality is an issue of equality, rights, and ethics, especially when it comes to the sexuality of people with intellectual and developmental disabilities. This paper offers a discussion of ethics related to the assessment and intervention supports of sexual behavior in people with intellectual and developmental disabilities. A brief history of sexuality and disability is presented. Issues of sexual abuse of people with intellectual and developmental disabilities and the laws related to sterilization, pornography, sexual rights, and consent are explored. Finally, specific ethical concerns related to intervention by behavior analysts in the realm of sexual behavior are examined.

Suppression of the Insulin Receptors in Adult Schistosoma japonicum Impacts on Parasite Growth and Development: Further Evidence of Vaccine Potential

To further investigate the importance of insulin signaling in the growth, development, sexual maturation and egg production of adult schistosomes, we have focused attention on the insulin receptors (SjIRs) of Schistosoma japonicum, which we have previously cloned and partially characterised. We now show, by Biolayer Interferometry, that human insulin can bind the L1 subdomain (insulin binding domain) of recombinant (r)SjIR1 and rSjIR2 (designated SjLD1 and SjLD2) produced using the Drosophila S2 protein expression system. We have then used RNA interference (RNAi) to knock down the expression of the SjIRs in adult S. japonicum in vitro and show that, in addition to their reduced transcription, the transcript levels of other important downstream genes within the insulin pathway, associated with glucose metabolism and schistosome fecundity, were also impacted substantially. Further, a significant decrease in glucose uptake was observed in the SjIR-knockdown worms compared with luciferase controls. In vaccine/challenge experiments, we found that rSjLD1 and rSjLD2 depressed female growth, intestinal granuloma density and faecal egg production in S. japonicum in mice presented with a low dose challenge infection. These data re-emphasize the potential of the SjIRs as veterinary transmission blocking vaccine candidates against zoonotic schistosomiasis japonica in China and the Philippines.