Search

PROLOGUE The slave-ships carried not only men, women and children, but also their gods, beliefs, and traditional folklore. So wrote the pioneering French Sociologist, Roger Bastide (1971, 23). When Columbus reached the Caribbean Islands in 1492, the American continent was populated by human communities whose social institutions and cultural patterns showed a remarkable diversity ranging from nomadic foragers like the Shoshoni and Paiute to complex theocratic states and civilizations – in its original sense – like the Aztec, Maya, and Inca (Farb 1969). The pattern of cultures that pre-existed the penetration and colonization of the American continent by European peoples, along with the developing market economy, to a large degree structured the subsequent division of the continent into what has been described as the ‘three Americas’ (Harris 1964). The temperate regions of the Americas, peopled largely by hunter–gatherers or shifting cultivators, were colonized by Europeans and now constitute ‘white’ America. In these regions, in countries such as the United States, Chile, and Argentina, the Native American population was largely eliminated through disease, forced labour, and genocide, and the majority of the population are now of European descent. In parts of Central and South America, however, the locus of the theocratic states of the Incas and Aztecs, the Native American population was high, and the Spanish and Portuguese colonizers, having conquered the region, simply supplanted the traditional elite and proceeded to rule these areas as imperial domains.

This paper questions whether a focus on individual development is appropriate when it comes to attempting to change professional practice. Based on a study of the conceptual development of candidates on the Scottish Qualification for Headship Programme (SQH), the paper examines evidence from detailed case studies of the learning of some of the students. These were constructed using the reflective commentaries written by the candidates at the end of each year and the outcomes of semi‐structured interviews to explore their experiences of the course and what they felt they had learned as a result. The evidence indicated that there was a complex dynamic involved in learning to change practice where the conceptual development of individuals was closely related to their experience of enacting new behaviours in the social setting of the workplace. The sense that candidates made of school leadership and management was shaped and embedded in their social experience. Change and development on their part was closely...

To investigate the contraception and sexual health-related awareness, attitudes, and practices of a representative sample of Canadian women of childbearing age.A self-report survey was mailed to a national sample of 3345 women, aged 15 to 44 years, who were members of a pre-recruited market research panel. Survey questions and methodology were similar to 3 previous Canadian Contraception Studies, allowing for description of current patterns of behaviours and beliefs and comparison of trends over time.Of 3345 women contacted, 1582 returned completed surveys, for a response rate of 47.3%. Responses were weighted to represent Canadian women by region, age, and marital status on the basis of current census data. Eighty-six percent of women sampled had ever had sexual intercourse and 78% were currently sexually active. Women's familiarity with oral contraceptives and condoms as methods of contraception was high (96% and 93%, respectively), but familiarity with other methods was much lower (sterilization, 62%; withdrawal, 59%; the morning-after pill, 57%; intrauterine devices, 50%; depot [injectable] medroxyprogesterone acetate, 38%). A very favourable opinion was held by 63% of respondents concerning oral contraceptives, by 38% concerning condoms, and by 39% and 28% concerning male and female sterilization, respectively. Among respondents who have ever had sexual intercourse, the most frequently used current methods were oral contraceptives (32%), condoms (21%), male sterilization (15%), female sterilization (8%), and withdrawal (6%). Nine percent of these respondents reported using no method of contraception at all. The currently reported rate of female sterilization is the lowest ever recorded in Canada. Survey results show that adherence to contraceptive methods is a challenge for many women and their partners, and that risk of sexually transmitted disease is an ongoing concern.This study provides a wide-ranging examination of contraception awareness, beliefs, and use among Canadian women that may provide guidance for clinical and public health practice. Part 1 of this report describes the methodology of the 2002 Canadian Contraception Study and the overall results of this study; Part 2 considers results pertaining specifically to adolescent women and women in their later reproductive years, reports on indicators of women's sexual function and reproductive health history, describes approaches to addressing challenges in contraception counselling, and presents data concerning trends in Canadian women's awareness and use of contraception over the past 2 decades.

Aim: Germline BRCA1/2 mutation screening is critical in ovarian cancer patients to identify a subset of women who might benefit from PARP inhibitors. A recent clinical study suggests that women with either germline or somatic BRCA1/2 mutations may benefit from PARP inhibitors1. Tumor mutation screening could expand the number of ovarian cancer patients that might consider PARP inhibitor treatment2. Methods: Previously untreated high grade epithelial ovarian cancer patients were prospectively enrolled between January 2011 and December 2013 in accordance with IRB protocol. Patients were offered germline and tumor BRCA1/2 mutation screening. Germline mutation screening was performed on DNA from blood via custom amplicon assay and next generation sequencing. DNA from FFPE tumor samples was sequenced using custom hybridization enrichment and next generation sequencing. Variants and large rearrangements were identified and classified according to established criteria. Results: 263 patients were enrolled and germline testing was completed. Germline mutation analysis revealed 39 deleterious mutations (15% mutation rate, 25 BRCA1 and 14 BRCA2 mutations). Somatic tumor analysis has been completed for 88 patients receiving upfront surgical treatment (out of 123 total upfront surgery patients). 14 (16%) had germline deleterious mutations and all 14 mutations were independently identified in the tumor, giving 100% concordance between the assays. An additional 8 (9%) deleterious somatic mutations were identified, representing an overall BRCA1/2 mutation rate of 25%. One somatic BRCA2 mutation was observed in a patient with a previously identified germline BRCA2 mutation. Conclusions: Data from this prospective cohort support previously reported frequencies of BRCA1/2 deleterious mutations in high grade epithelial ovarian tumors2. Next generation sequencing assays on blood and tumor DNA were 100% concordant. Tumor sequencing identified additional BRCA1/2 defects. Further molecular profiling and clinical follow-up is ongoing to evaluate outcomes in these subgroups of ovarian cancer patients with BRCA1/2 defects. References 1. Ledermann et al, 2013 ASCO Annual Meeting 2. Hennessy et al, 2010 JCO 28:3570-6. Disclosure: K. Timms, C. Neff, J. Potter, S. Chau, J. Chen, D. Williams, M. Perry, B. Morris, A. Gutin and J. Lanchbury: is an employee and stockholder of Myriad Genetics, Inc.; K. Lu: Participating MD Anderson researchers do not receive funds from Myriad Genetics, Inc.All other authors have declared no conflicts of interest.

In 1998, we conducted the first national survey of urology residents to evaluate Canadian training programs and other aspects related to the future practice of urology. The survey, a 7-page questionnaire, examined the educational learning needs of the trainees. Of 70 residents surveyed, 41 responded (response rate 60%). Topic areas in which the respondents felt comfortable included uro-oncology, and surgery of the prostate, kidney, and bladder. They were less comfortable with management of incontinence and infertility. In-training evaluation was thought to be an important activity that was well done by the training programs. A large majority (81%) expressed interest in elective rotations which they indicated should last 3 to 4 months. They suggested that research rotations be available, but not mandatory. There was strong support for the concept of a national examination preparation course. Almost half of the respondents indicated that American board examinations in urology were important in that it allowed them a choice between Canada and the United States. These results will be of use to those involved in the training of Canada's future urologists.

Abstract —Essential hypertensives display enhanced signal transduction through pertussis toxin–sensitive G proteins. The T allele of a C825T variant in exon 10 of the G protein β3 subunit gene ( GNB3 ) induces formation of a splice variant (Gβ3-s) with enhanced activity. The T allele of GNB3 was shown recently to be associated with hypertension in unselected German patients (frequency=0.31 versus 0.25 in control). To confirm and extend this finding in a different setting, we performed an association study in Australian white hypertensives. This involved an extensively examined cohort of 110 hypertensives, each of whom were the offspring of 2 hypertensive parents, and 189 normotensives whose parents were both normotensive beyond age 50 years. Genotyping was performed by polymerase chain reaction and digestion with Bse DI, which either cut ( C allele) or did not cut ( T allele) the 268-bp polymerase chain reaction product. T allele frequency in the hypertensive group was 0.43 compared with 0.25 in the normotensive group (χ 2 =22; P =0.00002; odds ratio=2.3; 95% CI=1.7 to 3.3). The T allele tracked with higher pretreatment blood pressure: diastolic=105±7, 109±16, and 128±28 mm Hg (mean±SD) for CC , CT , and TT , respectively ( P =0.001 by 1-way ANOVA). Blood pressures were higher in female hypertensives with a T allele ( P =0.006 for systolic and 0.0003 for diastolic by ANOVA) than they were in male hypertensives. In conclusion, the present study of a group with strong family history supports a role for a genetically determined, physiologically active splice variant of the G protein β3 subunit gene in the causation of essential hypertension.

There are opportunities to enhance the learning that takes place within computing projects in Higher Education in England and Wales. The application of Self Organised Learning (SOL) ideas in conjunction with teaching on Project Management for student negotiated self-selected computing projects for small to medium size enterprises has proved encouraging. The anatomy of learning conversations, found with SOL, has proved very useful in coaching students carrying out final year HND computing projects.

Homologous recombination (HR) repair defects are of potential therapeutic relevance in a variety of different cancers. Numerous studies have investigated the rate of BRCA1/2 mutations in triple negative breast cancer, and current clinical studies are investigating the efficacy of agents targeting HR deficiency in this breast cancer subtype. A more comprehensive assay for HR defects might expand the number of patients likely to benefit from these therapies, and may expand their utility to other breast cancer subtypes. Recently three DNA-based measures of HR deficiency (HRD) have been developed based on whole genome tumor LOH profiles, telomeric allelic imbalance, or large-scale state transitions. These will be referred herein as HRD-LOH, HRD-TAI and HRD-LST respectively. All 3 scores are highly correlated with defects in BRCA1/2 and other pathway genes in breast or ovarian cancer, and are associated with sensitivity to platinum agents. 213 invasive breast tumor samples and matched normal tissue blocks were obtained from 3 commercial vendors. The samples were selected to contain approximately equal numbers of all subtypes of breast cancer as defined by IHC analysis of ER, PR, and HER2. BRCA1/2 mutation screening and BRCA1 promoter methylation analysis was performed, and genome wide SNP profiles were generated. These data were used to calculate HRD-LOH, HRD-TAI, and HRD-LST scores. Somatic and germline BRCA1/2 mutations were detected in all subtypes of breast cancer at significant levels with the total mutation frequency ranging from 7.8 – 16.4% depending on subtype. In contrast BRCA1 promoter methylation was confined almost exclusively to triple negative tumors (19.7%). Overall BRCA1/2 deficiency ranged from approximately 10% in ER+/Her2- tumors up to approximately 36% in triple negative tumors. HRD-LOH, HRD-TAI, and HRD- LST scores have previously been shown to be highly significantly associated with BRCA1/2 status in both breast and ovarian cancer. In this dataset all 3 scores showed significant association with BRCA1/2 status for the entire dataset, in addition significant association was observed between the scores and BRCA1/2 status in each of the individual tumor subtypes. The 3 scores were found to be highly correlated with one another, but all 3 were still significant in multivariate analysis. This dataset is not of sufficient size to determine which of these scores is best able to identify BRCA1/2 deficient tumors. It is likely that a combination of the 3 scores will prove to be the most robust predictor of HR deficiency. This study has demonstrated significant levels of BRCA1/2 deficiency across all subtypes of breast cancer. All 3 HR deficiency assays showed significant association with BRCA1/2 deficiency regardless of breast cancer subtype. The 3 scores are highly correlated, but also additive and a combination of all 3 is likely to provide the best predictor of HR deficiency. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-05-10.

Introduction: Defects in homologous recombination (HR) repair have potential therapeutic relevance, and current clinical studies are focused on examining the efficacy of agents that exploit HR deficiency in triple negative breast cancer. A homologous recombination deficiency (HRD) score based on whole genome tumor LOH profiles has been developed that is highly correlated with defects in BRCA1/2, and other HR pathway genes, in ovarian cancer(1), and which predicts response to platinum-based neoadjuvant therapy in triple negative breast cancer(2). This study examines the frequency of BRCA1/2 defects and elevated HRD score across breast cancer subtypes as defined by IHC hormone receptor status. Methods: A targeted custom hybridization panel was developed targeting BRCA1, BRCA2, and 50,000 selected SNPs across the entire human genome. This panel, in combination with sequencing on the Illumina HiSeq, was used to analyze approximately 50 randomly ascertained tumors from each of 4 breast cancer subtypes (triple negative, ER+/Her2-, ER-/Her2+, ER+/Her2+) for BRCA1/2 somatic and germline mutations, and SNP allele frequencies. HRD scores were calculated using LOH profiles reconstructed from the SNP analysis. A BRCA1 promoter methylation assay was also performed on all samples. Results: BRCA1/2 somatic and germline mutations were detected in all breast cancer subtypes. BRCA1/2 mutations were observed most frequently in triple negative and ER+/Her2+ tumors. BRCA1 promoter methylation was confined almost exclusively to triple negative tumors. Association between elevated HRD score and BRCA defects was observed regardless of tumor type, and BRCA1/2 intact tumors with elevated HRD scores were observed in all breast cancer subtypes. Conclusions: Elevated HRD score is significantly associated with BRCA1/2 defects in breast cancer. BRCA1/2 defects and elevated HRD scores were observed in all subtypes of breast cancer, suggesting the presence of HR defects in genes other than BRCA1/2 are present in all breast cancer subtypes. HRD score could potentially be used to facilitate the expansion of platinum or PARP inhibitor therapy beyond triple negative breast cancer into other subtypes. Citation Format: Kirsten M. Timms, Victor Abkevich, Chris Neff, Brian Morris, Jennifer Potter, Thanh V. Tran, Jian Chen, Zaina Sangale, Eliso Tikishvili, Andrey Zharkikh, Michael Perry, Alexander Gutin, Jerry Lanchbury. Frequency of homologous recombination repair defects across breast cancer subtypes. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1763. doi:10.1158/1538-7445.AM2013-1763

The Canadian Urological Association has recently developed a new continuing medical education vehicle, Video Journal in Urology. The editorial content of this quarterly production is determined by the results of a needs assessment, the results of which are described in this paper. The needs assessment, as a two-page questionnaire, was mailed to 504 urologists. One hundred and eight-three responded, a response rate of 36.3%. The topic areas ranked as most interesting were largely centered around the broad topic of prostate cancer.

RFLPs at the low density lipoprotein receptor locus (LDLR) display marked linkage disequilibrium between each other. Cross-sectional analysis of a bi-alleleic ApaLI RFLP of LDLR showed that the 9.4- and 6.6-kb alleles were present in similar frequency between a group of 84 Caucasian essential hypertensive (HT) and a group of 96 normotensive subjects whose parents each had a similar blood pressure status at age > or = 50. After subdividing HTs into lean and obese, however, the frequency of the 6.6-kb allele in the 27 HTs with BMI > or = 26 kg/m2 was 0.63, compared with 0.39 for HTs with BMI < 26 (chi 2 = 8.8; P = 0.004). The difference in genotype frequencies was even more striking (chi 2 = 23; P = 0.00008), with a virtual absence of 9.4-kb homozygotes in the obese HT group (1 vs 22). Genetic variation at LDLR (19p13.2) is thus associated with obesity in HT.

Insulin has cardiovascular actions and patients with essential hypertension display insulin resistance. A cross-sectional study of the R1 RFLP of the insulin receptor gene (INSR) was carried out in 67 hypertensive (HT) and 75 normotensive (NT) subjects whose parents had a similar blood pressure status at age greater than or equal to 50. The frequency of the minor (+) allele was 0.31 in HTs and 0.44 in NTs, and the difference between observed alleles in all subjects in each group was significant (chi 2 = 4.8, P less than 0.05). Allele frequencies of a BglI RFLP of the insulin gene, however, did not differ between the HT and NT groups. The data thus provide evidence in favour of an association of HT with a polymorphism at the INSR locus (19p13.3-13.2), so implicating this locus, and possibly a genetic variant of the insulin receptor itself, in HT.