A historical argument for regulatory failure in the case of Primodos and other hormone pregnancy tests.

The drug Primodos and other hormone pregnancy tests (HPTs) remained on the British market for about a decade after they were first implicated, in 1967, as a possible cause of birth defects. In November 2017, an expert working group (EWG) set up by the Medicines and Healthcare Products Regulatory Agency (MHRA) concluded against such an association. However, it was explicitly 'not within the remit of the EWG to make formal conclusions or recommendations on the historical system or regulatory failures', a situation that has left many stakeholders dissatisfied. Placing the question of a teratogenicity to one side, this article takes a more contextual and comparative approach than was possible under the auspices of MHRA. It asks why an unnecessary and possibly even harmful drug was allowed to remain on the British market when a reliable and perfectly safe alternative existed: urine tests for pregnancy. Based on archival research in several countries, this article builds a historical argument for regulatory failure in the case of HPTs. It concludes that the independent review which campaigners are calling for would have the potential to not only bring them a form of closure, but would also shed light on pressing issues of more general significance regarding risk, regulation and communication between policy makers, medical experts and patients.The Wellcome Trust (Grant no. 106553), the Swedish Research Council (Dnr 446-2014–1749), and the University of Oslo

Breaking the silence : restorative justice and child sexual abuse : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Social Policy at Massey University, Albany, New Zealand

This research investigated the relationship between justice and child sexual abuse from the perspective of adult survivors. Utilising participant observation, unstructured interviews and focus groups within a feminist framework, 21 adult survivors of child sexual abuse (18 women and 3 men) were consulted to identify issues that were problematic for them. In addition, 2 jurors, 1 judge and 2 counsellors were interviewed. The findings indicated that child sexual abuse has been shrouded by a conspiracy of silence, caused partly by deeply entrenched structures within society. These forces combined with the complexity of recovery, including the possible impacts of Stockholm Syndrome, and the perceived inability of the criminal justice system to meet their needs, have appeared to silence many survivors of child sexual abuse. A review of the economic consequences and an analysis of the subsequent costs of child sexual abuse have indicated the need to implement programmes that would lessen the burden for victims, offenders, their families and the broader society. Survivors cautiously suggested that restorative justice might be sufficiently flexible to encourage victims of child sexual abuse to criminally report, thereby breaking the silence. A cost benefit analysis of a restorative justice programme indicated that significant savings could be made and highlighted that the prevention of child sexual abuse should be a priority. The findings of this research would have implications for policy makers and all those who provide services to victims and offenders of child sexual abuse. Stockholm Syndrome has highlighted the complexity of the recovery process for victims of child sexual abuse. This syndrome combined with the concerns of adult survivors of child sexual abuse would have implications for practitioners within the traditional criminal justice system and the restorative justice movement. Finally, the costs of child sexual abuse in New Zealand would have implications for justice agencies, health agencies, social welfare organisations and the Accident Compensation Corporation of New Zealand

Inherited human IRAK-1 deficiency selectively impairs TLR signaling in fibroblasts

Most members of the Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) families transduce signals via a canonical pathway involving the MyD88 adapter and the interleukin-1 receptor-associated kinase (IRAK) complex. This complex contains fourmolecules, including at least two (IRAK-1 and IRAK-4) active kinases. In mice and humans, deficiencies of IRAK-4 or MyD88 abolish most TLR (except for TLR3 and some TLR4) and IL-1R signaling in both leukocytes and fibroblasts. TLR and IL-1R responses areweak but not abolished inmice lacking IRAK-1, whereas the role of IRAK-1 in humans remains unclear. We describe here a boy with X-linked MECP2 deficiency-related syndrome due to a large de novo Xq28 chromosomal deletion encompassing both MECP2 and IRAK1. Like many boys with MECP2 null mutations, this child died very early, at the age of 7 mo. Unlikemost IRAK-4-or MyD88-deficient patients, he did not suffer from invasive bacterial diseases during his short life. The IRAK-1 protein was completely absent fromthe patient's fibroblasts, which responded very poorly to all TLR2/6 (PAM2CSK4, LTA, FSL-1), TLR1/2 (PAM3CSK4), and TLR4 (LPS, MPLA) agonists tested but had almost unimpaired responses to IL-1β. By contrast, the patient's peripheral blood mononuclear cells responded normally to all TLR1/2, TLR2/6, TLR4, TLR7, and TLR8 (R848) agonists tested, and to IL-1β. The death of this child precluded long-term evaluations of the clinical consequences of inherited IRAK-1 deficiency. However, these findings suggest that human IRAK-1 is essential downstream from TLRs but not IL-1Rs in fibroblasts, whereas it plays a redundant role downstream from both TLRs and IL-1Rs in leukocytes