Influence of CYP2D6 genotype on the disposition of the enantiomers of venlafaxine and its major metabolites in postmortem femoral blood

Venlafaxine (VEN) is an antidepressant drug mainly metabolized by the cytochrome P450 (CYP) enzyme CYP2D6 to the active metabolite O-desmethylvenlafaxine (ODV). VEN is also metabolized to N-desmetylvenlafaxine (NDV) via CYP3A4. ODV and NDV are further metabolized to N,O-didesmethylvenlafaxine (DDV). VEN is a racemic mixture of the S- and R-enantiomers and these have in vitro displayed different degrees of serotonin and noradrenaline reuptake inhibition. The aim of the study was to investigate if an enantioselective analysis of VEN and its metabolites, in combination with genotyping for CYP2D6, could assist in the interpretation of forensic toxicological results in cases with different causes of deaths. Concentrations of the enantiomers of VEN and metabolites were determined in femoral blood obtained from 56 autopsy cases with different causes of death. The drug analysis was done by liquid chromatography tandem mass spectrometry (LC/MS/MS) and the CYP2D6 genotyping by PCR and pyrosequencing. The mean (median) enantiomeric S/R ratios of VEN, ODV, NDV and DDV were 0.99 (0.91), 2.17 (0.93), 0.92 (0.86) and 1.08 (1.03), respectively. However, a substantial variation in the relationship between the S- and R-enantiomers of VEN and metabolites was evident (S/R ratios ranging from 0.23 to 17.6). In six cases, a low S/R VEN ratio (mean 0.5) was associated with a high S/R ODV ratio (mean 11.9). Genotyping showed that these individuals carried two inactive CYP2D6 genes indicating a poor metabolizer phenotype. From these data we conclude that enantioselective analysis of VEN and ODV can predict if a person is a poor metabolizer genotype/phenotype for CYP2D6. Knowledge of the relationship between the S- and R-enantiomers of this antidepressant drug and its active metabolite is also important since the enantiomers display different pharmacodynamic profiles.     

Sexual Harassment Litigation: a Road to Re-victimization or Recovery?

Various aspects of the judicial process have been hypothesized as damaging to sexual harassment plaintiffs, though limited research has been conducted that actually examines this hypothesis. We examined data from a large sample of women who participated in a class action lawsuit alleging workplace sexual harassment and discrimination (n?=?1218) and another sample of similarly situated women who opted out of litigation (n?=?465, non-litigants). We then followed the litigants for 5 years. This study takes an initial look at some of the variables theorized to play a role in the psychological outcomes of both harassment and subsequent litigation. Both the severity of harassment and participation/persistence in the litigation process were related to psychological outcomes at each of three assessments across a 5-year period; the frequency and severity of harassment, as well as plaintiffs’ cognitive appraisals of their situation, appeared to have the strongest relationship to psychological harm. Results of multivariate analysis of covariance (MANCOVA) revealed that participation and persistence in litigation played a consistent role in psychological outcomes across time, over and above the impact of harassment itself. However, litigation did not appear to be the cause of psychological outcomes as posttraumatic stress disorder (PTSD) symptomatology, in particular, was the result of the original harassment experience.     

A New Approach of Juvenile Age Estimation using Measurements of the Ilium and Multivariate Adaptive Regression Splines (MARS) Models for Better Age Prediction

Juvenile age estimation methods used in forensic anthropology generally lack methodological consistency and/or statistical validity. Considering this, a standard approach using nonparametric Multivariate Adaptive Regression Splines (MARS) models were tested to predict age from iliac biometric variables of male and female juveniles from Marseilles, France, aged 0–12 years. Models using unidimensional (length and width) and bidimensional iliac data (module and surface) were constructed on a training sample of 176 individuals and validated on an independent test sample of 68 individuals. Results show that MARS prediction models using iliac width, module and area give overall better and statistically valid age estimates. These models integrate punctual nonlinearities of the relationship between age and osteometric variables. By constructing valid prediction intervals whose size increases with age, MARS models take into account the normal increase of individual variability. MARS models can qualify as a practical and standardized approach for juvenile age estimation.     

Regulation of donor conception and the "time to tell" campaign

The first jurisdictions in the world to introduce legislation regulating donor conception were Victoria (Australia) and Sweden in the 1980s. Under the Infertility (Medical Procedures) Act 1984 (Vic), donor-conceived people (aged 18 years and over), their parents (if children were under 18 years) and donors gained the right to apply for identifying information about each other. Information can only be given with the consent of each party. To date, over 3,500 donor-conceived children have been born in Victoria since the 1984 Victorian legislation was introduced (and enacted in 1988). The first 106 donor-conceived children under this legislation turned 18 in 2006 and many of them may not know that they are donor-conceived. The Infertility Treatment Authority, Victoria, conducted a public education campaign to provide information and support to people affected by the legislation. The campaign and services associated with donor registers have had a significant initial impact.     

A review of the role of radical feminist theories in the understanding of rape myth acceptance

Abstract

Research into rape myth acceptance (RMA) first emerged in the 1970s, when authors such as Brownmiller (1975) and Burt (1980) proposed that rape was a mechanism that allowed men to exert power over women and that the endorsement of rape myths justified this sexual dominance. These influential theories have meant that subsequent definitions of rape myths have failed to acknowledge male victims of serious sexual assault, despite an increase in prevalence rates. More recent research has attempted to explore RMA in relation to male victims, with results suggesting that men are more likely than women to endorse rape myths regarding male victims when the victim is assumed to be homosexual, or when the victim is heterosexual and the perpetrator is female. Brownmiller's theory is challenged and a more holistic view of the importance of sex-role traditionality is explored, while acknowledging the contribution of individual factors relating to the development of RMA.     

Factors associated with contact child sexual abuse in a sample of indecent image offenders

Abstract

This study explored a sample of 244 UK adult male offenders convicted of offences involving indecent images of children (IIOC): 120 had a previous contact child sexual offence (defined as dual offenders) and 124 had no evidence of an offence against a child (defined as non-contact offenders). Offender groups were compared regarding their socio-demographic characteristics, previous convictions and IIOC possession. Key discriminatory factors that differentiated dual offenders were: access to children, previous offence history, sexual grooming and possession of IIOC that depicts similar-aged victims. In contrast, non-contact offenders could be identified from their greater amount and wider range of IIOC possession. The results suggest a homology between Internet behaviours, IIOC possession and victim selection. Implications for law enforcement agencies are discussed in terms of assisting investigative prioritisation by identifying those most at risk of committing sexual abuse against children.