"What Has This to Do with Working Class Women?": Birth Control and the Canadian Left, 1900-1939

Les études consacrées au mouvement canadien du contrôle des naissances ont jusqu’alors insisté sur le rôle joué par des philanthropes appartenant aux classes moyennes; elles ont ainsi maquillé le fait que ce furent d’abord des périodiques réformistes qui soulevèrent les aspects sociaux et politiques de la limitation des naissances. Les écrits des libertaires, des socialistes et des communistes révèlent que la gauche canadienne était loin de l’unanimité dans son évaluation des bienfaits de la contraception; elle se trouvait cependant à l’unisson dans son hostilité à ce qu’elle considérait comme une immixtion des classes moyennes dans la vie des familles ouvrières. Nous nous proposons ici à la fois d’étendre nos connaissances sur l’histoire du contrôle des naissances à ses débuts et de présenter sous un nouvel éclairage les attitudes de la gauche canadienne à l’endroit de la femme, de la famille et des agents de contrôle social

The longitudinal effects of midwife-led postnatal debriefing on the psychological health of mothers

To assess the effect of midwife-led postpartum debriefing on psychological variables, 149 women were recruited in the third trimester of their pregnancy and were randomly assigned to treatment and control conditions. Women in the treatment group received midwife-led postpartum debriefing within 3 days postpartum, whereas women in the control group did not receive formalised debriefing. Background information and psychological variables were assessed in the prepartum, and birthing information was gathered 2 days postpartum. The psychological variables, plus a measure of birth trauma, were re-assessed at 1 month, and again, together with a measure of parenting stress, at 3 months postpartum. Although the majority of women reported positively on their debriefing experience, statistical analyses indicated that only on the measure of dyadic satisfaction was there some suggestion that debriefing was effective. There were no significant differences between the treatment and control groups on measures of personal information, depression, anxiety, trauma, perception of the birth, or parenting stress at any assessment points, postpartum. On the other hand, the effect of medical intervention on women's perceptions of their birthing was evident, with women who experienced more medical intervention reporting more negative perceptions of their birthing than women who had experienced less medical intervention. Surprisingly, this difference was more marked among the women who had been debriefed than among the control group. Generally, the results did not support midwife-led debriefing as an effective intervention postpartum. © 2006 Society for Reproductive and Infant Psychology.C

'A tragedy as old as history':Medical responses to infertility and artificial insemination by donor in 1950s Britain

This chapter will explore how the infertile patient was characterized, perceived, and treated by the medical profession in 1950s England and Scotland. Such was the concern that this subject engendered in postwar Britain that a Departmental Committee was appointed in 1958 (known as the Feversham Committee) to investigate infertility and its treatment through artificial insemination. The written and oral evidence submitted by medical witnesses to that Committee offers rich insights into medical thinking and practice, and into the complex sociomedical politics and ethical anxieties which surrounded the topic. The testimony of legal and religious witnesses will also be explored to a more limited extent in order to offer some context to medical understandings and treatments of infertility. It will be considered how women’s bodies, personalities, and even agency in proactively seeking motherhood through artificial insemination were heavily pathologized in medical and religious discourses, but also how the men involved – husbands, sperm donors and even doctors – did not escape this tendency to pathologize

Mutational processes molding the genomes of 21 breast cancers

All cancers carry somatic mutations. The patterns of mutation in cancer genomes reflect the DNA damage and repair processes to which cancer cells and their precursors have been exposed. To explore these mechanisms further, we generated catalogs of somatic mutation from 21 breast cancers and applied mathematical methods to extract mutational signatures of the underlying processes. Multiple distinct single- and double-nucleotide substitution signatures were discernible. Cancers with BRCA1 or BRCA2 mutations exhibited a characteristic combination of substitution mutation signatures and a distinctive profile of deletions. Complex relationships between somatic mutation prevalence and transcription were detected. A remarkable phenomenon of localized hypermutation, termed "kataegis," was observed. Regions of kataegis differed between cancers but usually colocalized with somatic rearrangements. Base substitutions in these regions were almost exclusively of cytosine at TpC dinucleotides. The mechanisms underlying most of these mutational signatures are unknown. However, a role for the APOBEC family of cytidine deaminases is proposed

Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): Survival results from an adaptive, multiarm, multistage, platform randomised controlled trial

BACKGROUND Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone. METHODS Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m(2)) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544). FINDINGS 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60-71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6%) men were previously treated with local therapy, and median prostate-specific antigen was 65 ng/mL (IQR 23-184). Median follow-up was 43 months (IQR 30-60). There were 415 deaths in the control group (347 [84%] prostate cancer). Median overall survival was 71 months (IQR 32 to not reached) for SOC-only, not reached (32 to not reached) for SOC + ZA (HR 0·94, 95% CI 0·79-1·11; p=0·450), 81 months (41 to not reached) for SOC + Doc (0·78, 0·66-0·93; p=0·006), and 76 months (39 to not reached) for SOC + ZA + Doc (0·82, 0·69-0·97; p=0·022). There was no evidence of heterogeneity in treatment effect (for any of the treatments) across prespecified subsets. Grade 3-5 adverse events were reported for 399 (32%) patients receiving SOC, 197 (32%) receiving SOC + ZA, 288 (52%) receiving SOC + Doc, and 269 (52%) receiving SOC + ZA + Doc. INTERPRETATION Zoledronic acid showed no evidence of survival improvement and should not be part of standard of care for this population. Docetaxel chemotherapy, given at the time of long-term hormone therapy initiation, showed evidence of improved survival accompanied by an increase in adverse events. Docetaxel treatment should become part of standard of care for adequately fit men commencing long-term hormone therapy. FUNDING Cancer Research UK, Medical Research Council, Novartis, Sanofi-Aventis, Pfizer, Janssen, Astellas, NIHR Clinical Research Network, Swiss Group for Clinical Cancer Research

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio