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Background Breast reconstruction after mastectomy in the treatment of locally advanced breast cancer is often done in stages and before radiotherapy. We have previously published an algorithm for immediate free autologous reconstruction after neoadjuvant chemotherapy and preoperative radiotherapy. This protocol was designed to provide a shorter and simpler reconstructive path whilst improving cosmesis and maintaining oncological efficiency. Methods A total of 29 patients were included and underwent surgery for 30 cancers by the first author between 2010 and September 2015. Data were prospectively entered into a database and analysed for tumour size, chemotherapeutic response, lymph node involvement, surgical complications and tumour recurrence. Results The mean age was 55 ± 7 years. Eighty percent of patients had either a partial or complete chemotherapeutic response defined as >25% decrease in tumour size. Twenty-eight patients had free abdominal tissue transfer. One patient was excluded due to advanced disease. There were no take-backs due to microsurgical issues. One patient was reoperated on for a haematoma. Four patients had recurrent cancer during follow-up, three of whom are deceased. Conclusion Many, but not all, breast reconstructive surgeons consider autologous reconstruction as the 'gold' standard in the presence of radiotherapy. Rearranging the order of radiotherapy and surgery means operating in a recently irradiated field. We believe the surgical challenges are outweighed by a shorter and simpler reconstructive journey that additionally results in a better cosmesis. It is possible to perform immediate free autologous reconstruction after neoadjuvant chemotherapy and preoperative radiotherapy with excellent results and at least equivalent oncological efficacy.

Patient: Female, 66-year-old Final Diagnosis: Choriocarcinoma Symptoms: Vaginal bleeding Medication: — Clinical Procedure: — Specialty: Obstetrics and Gynecology Objective: Unusual clinical course Background: Choriocarcinoma is the most aggressive form of gestational trophoblastic disease and usually occurs in women of childbearing age, most commonly within 1 year after an abnormal pregnancy. Postmenopausal chorio-carcinoma is exceptionally rare and few cases have been described in the literature. Case Report: We present the case of a 66-year-old woman who presented to the Emergency Department with sudden onset of left upper- and lower-extremity weakness. She was found to have a brain mass, which was excised by neurosurgery and found to be a choriocarcinoma. She was then started on standard first-line therapy of EMACO, but was subsequently lost to follow-up. Conclusions: Postmenopausal choriocarcinoma is rare and there are few case reports in the literature. It is a rare but possibly under-diagnosed metastatic disease in women. At present, a postmenopausal woman without a clear primary tumor should have a pregnancy test performed to rule out choriocarcinoma, as it is readily responsive to therapy.

IntroductionThere is no power for change greater than a community discovering what it cares about.1 The Health Data Platform (HDP) will democratize British Columbia’s (population of approximately 4.6 million) health sector data by creating common enabling infrastructure that supports cross-organization analytics and research used by both decision makers and cademics. HDP will provide streamlined, proportionate processes that provide timelier access to data with increased transparency for the data consumer and provide shared data related services that elevate best practices by enabling consistency across data contributors, while maintaining continued stewardship of their data. HDP will be built in collaboration with Swansea University following an agile pragmatic approach starting with a minimum viable product. Objectives and ApproachBuild a data sharing environment that harnesses the data and the understanding and expertise about health data across academe, decision makers, and clinicians in the province by: Enabling a common harmonized approach across the sector on: Data stewardship Data access Data security and privacy Data management Data standards To: Enhance data consumer data access experience Increase process consistency and transparency Reduce burden of liberating data from a data source Build trust in the data and what it is telling us and therefore the decisions made Increase data accessibility safely and responsibly Working within the jurisdiction’s existing legislation, the Five Safes Privacy and Security Framework will be implemented, tailored to address the requirements of data contributors. ResultsThe minimum viable product will provide the necessary enabling infrastructure including governance to enable timelier access, safely to administrative data to a limited set of data consumers. The MVP will be expanded with another release planned for early 2021. Conclusion / ImplicationsCollaboration with Swansea University has enabled BC to accelerate its journey to increasing timelier access to data, safely and increasing the maturity of analytics by creating the enabling infrastructure that promotes collaboration and sharing of data and data approaches. 1 Margaret Wheatley

Iron deficiency is common worldwide and is associated with adverse pregnancy outcomes. The increasing prevalence of indiscriminate iron supplementation during pregnancy also raises concerns about the potential adverse effects of iron excess. We examined how maternal iron status affects the delivery of iron to the placenta and fetus. Using mouse models, we documented maternal homeostatic mechanisms that protect the placenta and fetus from maternal iron excess. We determined that under physiological conditions or in iron deficiency, fetal and placental hepcidin did not regulate fetal iron endowment. With maternal iron deficiency, critical transporters mediating placental iron uptake (transferrin receptor 1 [TFR1]) and export (ferroportin [FPN]) were strongly regulated. In mice, not only was TFR1 increased, but FPN was surprisingly decreased to preserve placental iron in the face of fetal iron deficiency. In human placentas from pregnancies with mild iron deficiency, TFR1 was increased, but there was no change in FPN. However, induction of more severe iron deficiency in human trophoblast in vitro resulted in the regulation of both TFR1 and FPN, similar to what was observed in the mouse model. This placental adaptation that prioritizes placental iron is mediated by iron regulatory protein 1 (IRP1) and is important for the maintenance of mitochondrial respiration, thus ultimately protecting the fetus from the potentially dire consequences of generalized placental dysfunction.

BACKGROUND: The role of cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) in the era of targeted therapies is currently undefined. In recent years, neutrophil-to-lymphocyte ratio (NLR) has emerged as a prognostic marker in several cancers, including mRCC. In this multicentre retrospective study, we aim to assess the impact of CN in mRCC and the value of NLR in risk stratification and patient selection. METHODS: Retrospective data from patients with de novo mRCC from four large Australian hospitals were collected. Survival analyses were performed using the Kaplan-Meier method and compared using the log-rank test. Multivariate analyses were performed using the Cox proportional hazards method. RESULTS: Our study identified 91 de novo mRCC patients. Patients who underwent CN (n = 46, 51%) were more likely to be younger (59.0 years vs 64.6 years, P = 0.019) and to have received systemic therapy (91% vs 76%, P = 0.043). Median overall survival (mOS) was significantly improved in patients who underwent CN (23.0 months vs 10.9 months, hazard ratios (HR) 0.33, 95% confidence interval (CI) 0.20-0.55, P

Background Hyperkyphosis negatively affects health status, physical mobility, and quality of life, but there is no standard protocol for treating people with hyperkyphosis. Treatment options include targeted exercise. Objectives This single-site randomized controlled trial (RCT) will determine the efficacy of a targeted multimodal spine-strengthening exercise program, compared with no exercise intervention, among community-dwelling men and women aged ≥60 years. Design The RCT is a parallel-group design, with 1:1 randomization to exercise and attentional control groups. Setting The study will be conducted at one primary site (one academic medical center partnered with one local community medical center). Participants One hundred men and women, aged ≥60 years, with thoracic kyphosis ≥40 degrees will be randomized. Intervention The targeted multimodal spine-strengthening exercise intervention includes exercise and postural training delivered by a physical therapist in a group of 10 participants, 3 times a week for 6 months. Controls receive monthly health education meetings in a group of 10 participants and monthly calls from the study coordinator to monitor physical activity and any adverse events. Measurements The primary outcome is change in Cobb angle of kyphosis measured from lateral spine radiographs at baseline and 6 months. Secondary outcomes include change in physical function (assessed with the modified Physical Performance Test, Timed “Up & Go” Test, timed loaded standing, 4-m walk, and Six-Minute Walk Test) and health-related quality of life (assessed with the modified Scoliosis Research Society instrument [SRS-30] self-image domain and Patient Reported Outcomes Measurement Information System [PROMIS] global health and physical function indexes). Additional secondary outcomes include pain, physical activity level, spinal flexion and extension muscle strength, paraspinal extensor muscle density, and adverse events. Limitations Blinding of the participants and instructors providing the intervention is not possible. Conclusions The efficacy of a high-quality, adequately powered exercise intervention in men and women with kyphosis ≥40 degrees will be evaluated to determine whether targeted multimodal spine-strengthening exercise reduces hyperkyphosis in older adults and improves important secondary outcomes of physical function and health-related quality of life.

276 Background: Ipilimumab and nivolumab (IPI-NIVO) and IO/vascular endothelial growth factor (VEGF) inhibitor combinations (IOVE) are now standard of care 1L treatment options for mRCC. However, there is limited head-to-head comparative evidence between these strategies. Methods: Using the IMDC dataset, patients treated with a 1L IOVE combination (pembrolizumab axitinib, avelumab axitinib and nivolumab cabozantinib) were compared with those treated with IPI-NIVO. The outcomes of interest were overall response rate (ORR), treatment duration (TD), time to next treatment (TTNT), and overall survival (OS). A preplanned subgroup analysis of the IMDC intermediate/poor risk population was conducted. Hazard ratios were adjusted for IMDC risk factors. Results: 723 patients were included for analysis (N=571 for IPI-NIVO and N=152 for IOVE). The median age was 60 in both groups. The proportion of patients with IMDC favorable, intermediate and poor risk disease in IPI-NIVO vs. IOVE groups were 9% vs. 33%, 58% vs. 53%, 33% vs. 14%, respectively. In the intermediate/poor risk groups (Table), ORR and median TD were lower and shorter in IPI-NIVO vs IOVE while no difference in median TTNT and OS was detected. The HR for death adjusting for IMDC criteria for IPI-NIVO vs. IOVE was 0.92 (95% CI 0.61-1.40, p=0.71). IMDC risk groups and the presence or absence of sarcomatoid histology, brain, liver or bone metastases were not associated with differences in OS between these treatments (all p>0.2). Patients that had dose delays or steroid use (defined as >40mg of prednisone equivalent/day) for immune related adverse events (irAEs) were associated with longer median TTNT (21.6 vs. 9.5 mons, p=0.02) and OS (NR vs. 44.4 mons, p=0.01) despite similar treatment durations (7.6 vs. 8.9 mons, p=0.77) compared to those without dose delays or steroid use. Conclusions: We were unable to detect any differences in OS between IPI-NIVO and IOVE regimens in the IMDC intermediate/poor risk groups and amongst various subgroups. Patients who experienced irAEs requiring dose delay or steroids had longer overall survival. [Table: see text]

BACKGROUND: Hyperkyphosis is common among older adults, and is associated with multiple adverse health outcomes. A kyphosis-specific exercise and posture training program improves hyperkyphosis, but in-person programs are expensive to implement and maintain over longer-periods of time. It is unknown if a technology-based posture training program disseminated through a smartphone is a feasible or acceptable alternative to in-person training among older adults with hyperkyphosis. OBJECTIVE: The primary purpose of this study was to assess the feasibility of subject recruitment, short-term retention and adherence, and the acceptability of a technology-based exercise and postural training program disseminated as video clip links and text messaging prompts via a smartphone. The secondary purpose was to explore the potential efficacy of this program on kyphosis, physical function and health-related quality of life in older adults with hyperkyphosis METHODS: This was a 6-week pre-post design pilot trial. We recruited community-dwelling adults ≥65 years with hyperkyphosis ≥40 (±5) degrees and access to a smartphone. The intervention had two parts: 1) exercise and posture training via video clips sent to participants daily via text messaging which included 6 weekly video clip links to be viewed on the participant’s smartphone and 2) text messaging prompts to practice good posture. We determined subject recruitment, adherence, retention and acceptability of the intervention. Outcomes included change in kyphometer-measured kyphosis, occiput to wall (OTW), Short Physical Performance Battery (SPPB), Scoliosis Research Society SRS-30, Center for Epidemiological Studies Depression (CESD) and Physical Activity Scale for the Elderly (PASE). RESULTS: 64 potential participants were recruited, 17 participants were enrolled and 12 completed post-intervention testing at 6-weeks. Average age was 71.6 (SD=4.9) years and 50% were female. Median adherence to daily video viewing was 100%, (range 14 to 100) and to practicing good posture 3 times or more per day was 71%, (range 0 to 100). Qualitative evaluation of acceptability of the intervention revealed the smartphone screen was too small for participants to view the videos well and daily prompts to practice posture were too frequent. Kyphosis, OTW and physical activity significantly improved after the 6-week intervention. Kyphosis decreased by 8 (95% CI: 12, 5) degrees (p

Although viral vectors comprise the majority of gene delivery vectors, their various safety, production, and other practical concerns have left a research gap to be addressed. The non-viral vector space encompasses a growing variety of physical and chemical methods capable of gene delivery into the nuclei of target cells. Major physical methods described in this chapter are microinjection, electroporation, and ballistic injection, magnetofection, sonoporation, optical transfection, and localized hyperthermia. Major chemical methods described in this chapter are lipofection, polyfection, gold complexation, and carbon-based methods. Combination approaches to improve transfection efficiency or reduce immunological response have shown great promise in expanding the scope of non-viral gene delivery.

[Purpose] Persons with age-related hyperkyphosis often have concomitant sagittal plane imbalance of the spine. This study investigated the reliability of sagittal vertical axis (SVA) measurement of sagittal balance, association between thoracic Cobb angle of kyphosis and SVA measure of sagittal balance, and compared the degree of SVA in males and females with age-related hyperkyphosis. [Participants and Methods] Measurements of SVA and Cobb angle of kyphosis were obtained from baseline radiographs of 112 community-dwelling males and females, mean age 70.0 (SD=5.7) years with kyphosis ≥40 degrees, recruited for a randomized controlled trial. Spearman correlation coefficients were used to determine associations between SVA and kyphosis, and Wilcoxon nonparametric tests to compare SVA between genders. [Results] SVA was acquired with excellent intra-rater [0.95 (95% CI: 0.88, 0.98)] and inter-rater reliability [0.93 (95% CI: 0.83,0.97)]. There was no significant correlation between Cobb angle of thoracic kyphosis and SVA, (r=−0.05). More males than females had sagittal imbalance (SVA≥5 cm). [Conclusion] In older adults with hyperkyphosis, SVA was a reliable measure of sagittal balance, and more extreme in males. SVA was not associated with Cobb angle of thoracic kyphosis, and could be considered an independent phenotype of age-related hyperkyphosis to be targeted in future intervention trials.

Purpose: Preclinically, AKT kinase inhibition restores drug sensitivity in platinum-resistant tumors. Here the pan-AKT kinase inhibitor afuresertib was given in combination with paclitaxel and carboplatin (PC) in patients with recurrent platinum-resistant epithelial ovarian cancer (PROC) and primary platinum-refractory ovarian cancer (PPROC). Patients and Methods: Part I was a combination 3+3 dose escalation study for recurrent ovarian cancer. Patients received daily continuous oral afuresertib at 50–150 mg/day with intravenous paclitaxel (175 mg/m2) and carboplatin (AUC5) every 3 weeks for six cycles followed by maintenance afuresertib at 125 mg/day until progression or toxicity. Part II was a single-arm evaluation of the clinical activity of this combination in recurrent PROC (Cohort A) or PPROC (Cohort B). Patients received oral afuresertib at the MTD defined in Part I in combination with PC for six cycles, followed by maintenance afuresertib. Primary endpoints were safety and tolerability of afuresertib in combination with PC (Part I, dose escalation), and investigator-assessed overall response rate (ORR) as per RECIST version 1.1 (Part II). Results: Twenty-nine patients enrolled into Part I, and 30 into Part II. Three dose-limiting toxicities of grade 3 rash were observed, one at 125 mg and two at 150 mg afuresertib. The MTD of afuresertib in combination with PC was therefore identified as 125 mg/day. The most common (≥50%) drug-related adverse events observed in Part I of the study were nausea, diarrhea, vomiting, alopecia, fatigue, and neutropenia and, in Part II, were diarrhea, fatigue, nausea, and alopecia. The Part II ORR in the intention to treat patients was 32% [95% confidence interval (CI), 15.9–52.4] by RECIST 1.1 and 52% (95% CI, 31.3–72.2) by GCIG CA125 criteria. Median progression-free survival was 7.1 months (95% CI, 6.3–9.0 months). Conclusions: Afuresertib plus PC demonstrated efficacy in recurrent PROC with the MTD of afuresertib defined as 125 mg/day.

BACKGROUND: The impact of regulatory approvals of new therapies for castration-resistant prostate cancer (CRPC) in Australia is unclear. AIMS: To determine if changes in novel therapy access in Australia affected how clinicians initially managed men with newly diagnosed CRPC. METHODS: Data from patients diagnosed with CRPC from 2013 to 2016 across three Australian hospitals were retrospectively collected. Baseline clinicopathological factors and initial management decision at the time of CRPC development (early treatment (ET) vs deferred treatment (DT)) were recorded. Categorical variables between cohorts were compared by Chi-squared analysis. Cox regression analysis was performed to assess the impact of CRPC diagnosis year on time to commencing life-prolonging systemic treatment (TTT). RESULTS: Our study identified 137 CRPC patients, with 126 (92%) patients receiving life-prolonging systemic treatment. The median age was 73 years. The initial management decision was DT in 71 (52%) patients and ET in 66 (48%) patients. There was a significant shift from DT to ET during the study period (2013-2014: DT 61% vs ET 33%; 2015-2016: DT 39% vs ET 67%; P = 0.004), with a rise in novel androgen receptor signalling inhibitor use and simultaneous reduction in first-generation antiandrogen use at CRPC development. Each successive CRPC diagnosis year was associated with shorter TTT on univariate analysis (HR: 1.5, 95% CI: 1.3-1.7, P < 0.001). CONCLUSION: Over time, clinicians are favouring earlier introduction of life-prolonging systemic treatment at the development of CRPC. This trend is largely driven by substantial uptake of novel androgen receptor signalling inhibitors as the preferred initial treatment for CRPC patients.

BACKGROUND Hyperkyphosis is common among older adults and is associated with multiple adverse health outcomes. Kyphosis-specific exercise and posture training programs improve hyperkyphosis, but in-person programs are expensive to implement and maintain over long periods. It is unclear if a technology-based posture training program disseminated through a mobile phone is a feasible or acceptable alternative to in-person training among older adults with hyperkyphosis. OBJECTIVE The primary purpose was to assess the feasibility of subject recruitment, short-term retention and adherence, and acceptability of a technology-based exercise and posture training program disseminated as video clip links and text messaging prompts via a mobile phone. The secondary purpose was to explore the potential efficacy of this program for kyphosis, physical function, and health-related quality of life in older adults with hyperkyphosis. METHODS In this 6-week pre-post design pilot trial, we recruited community-dwelling adults aged ≥65 years with hyperkyphosis ≥40° (±5°) and access to a mobile phone. The intervention had two parts: (1) exercise and posture training via video clips sent to participants daily via text messaging, including 6 weekly video clip links to be viewed on the participant’s mobile phone, and (2) text messaging prompts to practice good posture. We analyzed the subject recruitment, adherence, retention, and acceptability of the intervention. Outcomes included change in kyphometer-measured kyphosis, occiput-to-wall (OTW) distance, Short Physical Performance Battery score, Scoliosis Research Society (SRS-30) score, Center for Epidemiological Studies Depression score, and Physical Activity Scale for the Elderly (PASE) score. RESULTS A total of 64 potential participants were recruited, 17 were enrolled, and 12 completed postintervention testing at 6 weeks. The average age was 71.6 (SD 4.9) years, and 50% were women. The median adherence to daily video viewing was 100% (range, 14%-100%) and to practicing good posture at least three times per day was 71% (range, 0%-100%). Qualitative evaluation of intervention acceptability revealed that the mobile phone screen was too small for participants to view the videos well and daily prompts to practice posture were too frequent. Kyphosis, OTW distance, and physical activity significantly improved after the 6-week intervention. Kyphosis decreased by 8° (95% CI –12 to –5; P CONCLUSIONS Technology-based exercise and posture training using video clip viewing and text messaging reminders is feasible and acceptable for a small cohort of older adults with hyperkyphosis. Technology-based exercise and posture training warrants further study as a potential self-management program for age-related hyperkyphosis, which may be more easily disseminated than in-person training.

IntroductionBC’s Ministry of Health (MOH) maintains many administrative databases with rich information and analytical potential. Researchers are keen to use these data for both discovery and applied research. Historically, limited views of data availability and populations therein have supported study feasibility. Therefore, we developed BC Data ScoutTM, a cohort browser. Objectives and ApproachWe developed a cohort browser service to provide information to researchers planning a study using MOH data. The objective was to create a tool that is simple to use, provides quick results and is free to users to encourage its use. A better understanding of the data available can improve study quality and expand the user-base by giving researchers access to information not previously available during the planning stages. The tool will be evaluated by examining the number of requests received and a user satisfaction survey. Plans are in place to expand into additional data sources and extend query sophistication. ResultsThe BC Data ScoutTM online tool provides cohort information in the form of highly aggregated, approximate results to researchers planning a study. It was developed by the MOH, the BC SUPPORT Unit and Population Data BC (PopData) and was launched in February 2018. The service is delivered by PopData. BC Data ScoutTM offers province-wide information for query, is accessible to a wide group of eligible researchers, and has data availability from the year 2000 onwards. Four types of MOH data are available for query: hospital data; physician data; pharmaceutical data; and demographics. In addition to determining study feasibility, the aggregate reports also help to further refine a full data access request and provide enough information to complete and strengthen a funding application. Conclusion/ImplicationsBC Data ScoutTM will be beneficial for researchers planning to request data. This preliminary information may increase the chances of meaningful research studies to obtain funding, and the production of relevant, high-quality research results. BC will be among the first jurisdictions across Canada to offer this type of feasibility service.

There is an increasing need for new cancer therapies. The antitumour effect of bacterial infection has been well observed and practiced throughout history. Bacteria are well-suited to serve as anticancer agents due to their intrinsic mobility, cell toxicity, immunogenicity, and preferential accumulation within the anoxic tumour environment. Furthermore, advances in biotechnology and molecular techniques have made it easier than ever to engineer bacteria as both therapeutic agents themselves and as therapeutic vectors. Here, we review bacteriolytic therapy and immunotherapy strategies, and examine the development of bacteria as vehicles for cell- and tissue-targeted delivery of genetic cancer therapeutics.

Androgen deprivation and androgen targeted therapies (ATT) are established treatments for prostate cancer (PCa). Although initially effective, ATT induces an adaptive response that leads to treatment resistance. Increased expression of relaxin-2 (RLN2) is an important alteration in the adaptive response. RLN2 has a well described role in PCa cell proliferation, adhesion and tumour growth. The objectives of this study were to develop cell models for studies of RLN2 signalling and to implement in vitro assays for evaluating the therapeutic properties of the unique RLN2 receptor (RXFP1) antagonist

Although viral vectors comprise the majority of gene delivery vectors, their various safety, production, and other practical concerns have left a research gap to be addressed. The non-viral vector space encompasses a growing variety of physical and chemical methods capable of gene delivery into the nuclei of target cells. Major physical methods described in this chapter are microinjection, electroporation, and ballistic injection, magnetofection, sonoporation, optical transfection, and localized hyperthermia. Major chemical methods described in this chapter are lipofection, polyfection, gold complexation, and carbon-based methods. Combination approaches to improve transfection efficiency or reduce immunological response have shown great promise in expanding the scope of non-viral gene delivery.

The paper investigates the inherent problems of financial fraud detection and proposes a forensic accounting framework using business intelligence as a plausible means of addressing them. The paper adopts an empirical case study approach to present how business intelligence could be used effectively in the detection of financial accounting fraud. The proposed forensic accounting framework using business intelligence (BI) provides a three-phase model via novel knowledge discovery technique to perform the financial analysis such as ratio analysis for a business case scenario. The implementation of the framework practically demonstrates by using their accounting data how the technologies and the investigative methods of trend analysis could be adopted in order to investigate fraudulent financial reporting unlike traditional methods of vertical and horizontal analysis for the business case study. Finally, the results justify the effectiveness of the proposed BI model in proactively identifying, classifying and evaluating financial fraud in the organisation. This research further leads to practical follow-up steps that would serve as guidelines for the forensic accounting auditors and management to focus on the prime areas of financial fraud present in the case study. Overall, the proposed model caters to detecting various types of accounting fraud as well as aids in continuous improvement of an organisation?s accounting, audit, systems and policies through the feedback loop.

BACKGROUND:Hyperkyphosis, an excessive anterior curvature in the thoracic spine, is associated with reduced health status in older adults. Hyperkyphosis is highly prevalent, more common in older women than men. There is no standard intervention to reduce age-related hyperkyphosis. Sex differences in response to a kyphosis-specific exercise intervention are not known. METHODS:We conducted a randomized controlled trial of a targeted kyphosis-specific exercise and postural training program on the primary outcome Cobb angle of kyphosis, and investigated whether the magnitude of change differed between men and women. One hundred twelve participants aged ≥60years with kyphosis ≥40° were enrolled and randomized to exercise or waitlist control, and 101 participants had analyzable baseline and follow-up radiographs for Cobb angle measurements. A group intervention including 10 participants per group was delivered by a physical therapist, 1-h, twice a week for 3-months. Controls were placed on a waitlist for 3months before receiving a delayed intervention. Primary outcome was change from baseline to 3-months in Cobb angle measured from standing lateral spine radiographs. Secondary outcomes included change over 3-months in kyphometer-measured kyphosis, physical function and quality of life. Groups were combined for analysis after both received the intervention, and sex differences in response to the intervention were tested with ANOVA. RESULTS:Participants (60 women, 41 men) were 70.0 (SD = 5.7) years old with mean Cobb angle 55.9 (SD = 12.2) degrees at baseline. The active group had higher baseline modified Physical Performance Test scores than control, p= 0.03. Men had greater baseline kyphometer-measured kyphosis, p= 0.09, and higher bone mineral density (BMD), spine strength, more vertebral fractures and diffuse idiopathic skeletal hyperostosis (DISH) than women, p≤ 0.01. There was no statistically significant difference between groups in change in Cobb at 3-months, p = 0.09, however change in kyphometer-measured kyphosis differed by 4.8 (95% CI:-6.8,-2.7) degrees, p 0.1. CONCLUSIONS:A 3-month targeted spine strengthening exercise and posture training program reduced kyphometer-measured, but not radiographic-measured kyphosis. Despite sex differences in baseline kyphosis, BMD, spine strength, fractures and DISH, sex did not affect treatment response. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT01766674.

© 2017, International Osteoporosis Foundation and National Osteoporosis Foundation. Summary: A 6-month randomized controlled trial of spine-strengthening exercise and posture training reduced both radiographic and clinical measures of kyphosis. Participants receiving the intervention improved self-image and satisfaction with their appearance. Results suggest that spine-strengthening exercise and postural training may be an effective treatment option for older adults with hyperkyphosis. Introduction: The purpose of the present study is to determine in a randomized controlled trial whether spine-strengthening exercises improve Cobb angle of kyphosis in community-dwelling older adults. Methods: We recruited adults ≥60 years with kyphosis ≥40° and enrolled 99 participants (71 women, 28 men), mean age 70.6 ± 0.6 years, range 60–88, with baseline Cobb angle 57.4 ± 12.5°. The intervention included group spine-strengthening exercise and postural training, delivered by a physical therapist, 1-h, three times weekly for 6 months. Controls received four group health education meetings. The primary outcome was change in the gold standard Cobb angle of kyphosis measured from standing lateral spine radiographs. Secondary outcomes included change in kyphometer-measured kyphosis, physical function (modified Physical Performance Test, gait speed, Timed Up and Go, Timed Loaded Standing, 6-Min Walk), and health-related quality of life (HRQoL) (PROMIS global health and physical function indexes, SRS-30 self-image domain). ANCOVA was used to assess treatment effects on change from baseline to 6 months in all outcomes. Results: There was a −3.0° (95% CI −5.2, −0.8) between-group difference in change in Cobb angle, p = 0.009, favoring the intervention and approximating the magnitude of change from an incident vertebral fracture. Kyphometer-measured kyphosis (p = 0.03) and SRS-30 self-esteem (p 0.05. Conclusions: Spine-strengthening exercise and posture training over 6 months reduced kyphosis compared to control. Our randomized controlled trial results suggest that a targeted kyphosis-specific exercise program may be an effective treatment option for older adults with hyperkyphosis. Trial registration number and name of trial register: ClinicalTrials.gov; identifier NCT01751685.

The current taxonomy of the order Xanthomonadales is highly problematic and no comprehensive phylogenomic studies have been completed that include the most divergent members within the order. In this work, we have completed a phylogenomic analysis of a wide range of genomes, five of which were sequenced for the first time for this work, representing the vast majority of the diversity within the order Xanthomonadales. Using comparative genomic techniques, we have identified a large number of conserved signature inserts/deletions (CSIs) that are specifically found in different groups of related organisms, at different taxonomic levels, within the order. Our phylogenetic analyses do not support a monophyletic grouping of the members of the order Xanthomonadales and no CSIs were identified which are uniquely shared by all sequenced species within this order. However, our work has identified 10 CSIs which are specific to all members of the family Xanthomonadaceae and an additional 10 and 11 CSIs that are specific to one of two phylogenetically well-defined clades within the family Xanthomonadaceae. On the basis of the identified CSIs and the results of phylogenomic analyses, we propose a new taxonomic framework for the order Xanthomonadales. In this proposal, the families Algiphilaceae and Solimonadaceae (Nevskiaceae), which do not branch with the other members of the order Xanthomonadales, are transferred into the order Nevskiales ord. nov. The remaining members of the order Xanthomonadales are divided into two families: the family Xanthomonadaceae, containing the genus Xanthomonas and its closest relatives, and a new family, Rhodanobacteraceae fam. nov., containing the genus Rhodanobacter and its closest relatives. Additionally, we have also emended descriptions of the order Lysobacterales, the family Lysobacteraceae, and the family Nevskiaceae to indicate that they are earlier synonyms of the order Xanthomonadales, the family Xanthomonadaceae, and the family Solimonadaceae, respectively.

Objective To examine the tolerability and antitumor activity of trebananib plus pegylated liposomal doxorubicin (PLD) or topotecan in recurrent platinum-resistant or partially platinum-sensitive ovarian cancer. Methods In this open-label phase 1b study, patients received trebananib 10mg/kg or 15mg/kg IV QW plus PLD 50mg/m 2 (cohorts A1 and A3, respectively) or topotecan 4mg/m 2 (cohorts B1 and B3, respectively). Endpoints were dose-limiting toxicity (DLT; primary); treatment-emergent adverse events (AEs), overall response rate, anti-trebananib antibodies, and pharmacokinetics (secondary). Results 103 patients were enrolled. One patient in A1 and B1 had DLTs. Across all cohorts, the most common AEs were nausea, fatigue, and peripheral edema. Across both trebananib plus PLD cohorts (A1/A3), grade 4 AEs were pulmonary embolism, disease progression, and anemia. Two patients had grade 5 intestinal perforation (n=1) and sudden death (n=1). Across both trebananib plus topotecan cohorts (B1/B3), grade 4 AEs were neutropenia, hypokalemia, decreased granulocyte count, chest pain, dyspnea, decreased neutrophil count, and pulmonary embolism. Two patients had grade 5 disease progression. One patient had grade 5 pleural effusion associated with progressive disease. Confirmed objective response rates were 36.0% (A1), 34.8% (A3), 16.7% (B1), and 0.0% (B3). Median progression-free survival duration (months) was 7.4 (A1), 7.1 (A3), 3.5 (B1), and 3.1 (B3), respectively. No drug–drug interactions were apparent. Conclusions Trebananib 10mg/kg and 15mg/kg IV QW plus PLD or topotecan appear to have acceptable toxicity profiles in recurrent platinum-resistant or partially platinum-sensitive ovarian cancer. Antitumor activity was evident across all cohorts.

Enterohemorrhagic Escherichia coli O157:H7 is responsible for many outbreaks of gastrointestinal illness and hemolytic uremic syndrome worldwide. Monitoring this pathogen in food and water supplies is an important public health issue. Highly conserved genetic markers, which are characteristic for specific strains, can provide direct identification of target pathogens. In this study, we examined a new detection strategy for pathogenic strains of E. coli O157:H7 serotype based on a conserved signature insertion/deletion (CSI) located in the ybiX gene using TaqMan-probe-based quantitative PCR (qPCR). The qPCR assay was linear from 1.0 × 10(2) to 1.0 × 10(7) genome copies and was specific to O157:H7 when tested against a panel of 15 non-O157:H7 E. coli. The assay also maintained detection sensitivity in the presence of competing E. coli K-12, heterologous nontarget DNA spiked in at a 1000-fold and 800-fold excess of target DNA, respectively, demonstrating the assay's ability to detect E. coli O157:H7 in the presence of high levels of background DNA. This study thus validates the use of strain-specific CSIs as a new class of diagnostic marker for pathogen detection.

Polypeptides have received noticeable attention in the biomedical field due to their structural versatility and biomimetic properties. Particularly, polypeptides that are responsive to biological stimuli, such as mildly acidic extracellular and intracellular conditions, have great potential as delivery carriers for therapeutics. However, synthesis of high-molecular-weight acid-labile peptides is often daunting due to highly restrictive polymerization conditions and limitations in preserving acid-degradable functional groups. For instance, the popular N-carboxyanhydride (NCA) ring-opening polymerization (ROP) is efficient, but acid-labile NCA monomers are difficult to synthesize and store. In this study, acid-labile polypeptides with high molecular weights were synthesized under mild, permissive conditions using carboxylated urethane derivative monomers which are stable for ease of handling. The polymerization was successful in various organic solvents at room temperature, and did not require additional energy or initiation to drive the formation of NCA intermediates. The polymerization was also rapid enough to be independent of inert atmosphere. The strategy explored here to synthesize high-molecular-weight acid-labile polypeptides offers significant advantages including facile synthesis of acid-labile urethane derivative monomers that are stable, even in contact with moisture, and fast polymerization under easily achievable conditions. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 280–286

Background Current treatment for locally advanced breast cancer (LABC) includes neoadjuvant chemotherapy and post-mastectomy radiotherapy, which may be deleterious for immediate reconstruction. A few trials have instead combined neoadjuvant chemotherapy followed by preoperative radiotherapy. If safe and oncologically efficacious, mastectomy with immediate free autologous reconstruction (transverse rectus abdominis myocutaneous (TRAM)/deep inferior epigastric perforator (DIEP) flap) could then achieve a shorter, simpler reconstructive journey with better cosmesis. No trials have been performed combining this neoadjuvant regime with free autologous reconstruction as an assessment end point. Methods We performed a Pubmed/Medline search for oncological efficacy of neoadjuvant chemotherapy followed by preoperative radiotherapy and flap reconstruction of the breast. A new treatment sequencing protocol is proposed in which patients suitable for neoadjuvant chemotherapy followed by preoperative radiotherapy and likely mastectomy are selected. Positive chemotherapeutic response is followed by radiotherapy then surgery within 6 weeks comprising mastectomy/axillary clearance and immediate reconstruction (TRAM/DIEP). Non-responders are offered mastectomy, tissue expander reconstruction, adjuvant radiotherapy then delayed autologous reconstruction. Local/systemic recurrence rates, disease-free survival, complications, patient satisfaction and aesthetics are examined. Results Between 1995 and 2012, 10 trials treated LABC patients using combined neoadjuvant chemotherapy followed by preoperative radiotherapy. Compared with chemotherapy alone, increased complete pathological response, complete clinical remission, median survival and tumour-free survival were observed. Discussion Our new treatment sequence protocol offers a simpler, more advantageous approach to LABC. We hypothesize equivalent oncological efficacy, optimized oncological management and surgical planning. The aim was to shorten and simplify the reconstructive journey through a single operation including gold-standard reconstruction, offering better cosmesis, fewer complications and reduced costs.

Summary Background Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab—a human IgG1 VEGFR-2 antagonist—or placebo in this patient population. Methods We did a randomised, double-blind, phase 3 trial in patients with advanced or metastatic urothelial carcinoma who progressed during or after platinum-based chemotherapy. Patients were enrolled from 124 sites in 23 countries. Previous treatment with one immune-checkpoint inhibitor was permitted. Patients were randomised (1:1) using an interactive web response system to receive intravenous docetaxel 75 mg/m 2 plus either intravenous ramucirumab 10 mg/kg or matching placebo on day 1 of repeating 21-day cycles, until disease progression or other discontinuation criteria were met. The primary endpoint was investigator-assessed progression-free survival, analysed by intention-to-treat in the first 437 randomised patients. This study is registered with ClinicalTrials.gov, number NCT02426125. Findings Between July, 2015, and April, 2017, 530 patients were randomly allocated either ramucirumab plus docetaxel (n=263) or placebo plus docetaxel (n=267). Progression-free survival was prolonged significantly in patients allocated ramucirumab plus docetaxel versus placebo plus docetaxel (median 4·07 months [95% CI 2·96–4·47] vs 2·76 months [2·60–2·96]; hazard ratio [HR] 0·757, 95% CI 0·607–0·943; p=0·0118). A blinded independent central analysis was consistent with these results. An objective response was achieved by 53 (24·5%, 95% CI 18·8–30·3) of 216 patients allocated ramucirumab and 31 (14·0%, 9·4–18·6) of 221 assigned placebo. The most frequently reported treatment-emergent adverse events, regardless of causality, in either treatment group (any grade) were fatigue, alopecia, diarrhoea, decreased appetite, and nausea. These events occurred predominantly at grade 1–2 severity. The frequency of grade 3 or worse adverse events was similar for patients allocated ramucirumab and placebo (156 [60%] of 258 vs 163 [62%] of 265 had an adverse event), with no unexpected toxic effects. 63 (24%) of 258 patients allocated ramucirumab and 54 (20%) of 265 assigned placebo had a serious adverse event that was judged by the investigator to be related to treatment. 38 (15%) of 258 patients allocated ramucirumab and 43 (16%) of 265 assigned placebo died on treatment or within 30 days of discontinuation, of which eight (3%) and five (2%) deaths were deemed related to treatment by the investigator. Sepsis was the most common adverse event leading to death on treatment (four [2%] vs none [0%]). One fatal event of neutropenic sepsis was reported in a patient allocated ramucirumab. Interpretation To the best of our knowledge, ramucirumab plus docetaxel is the first regimen in a phase 3 study to show superior progression-free survival over chemotherapy in patients with platinum-refractory advanced urothelial carcinoma. These data validate inhibition of VEGFR-2 signalling as a potential new therapeutic treatment option for patients with urothelial carcinoma. Funding Eli Lilly and Company.

This paper briefly introduces the framework of an early diagnosis and early intervention program for Hong Kong pre-school children with special educational needs launched by the Counselling & Research Center at the Hong Kong Shue Yan University and Lok Sin Tong (a charitable organization established under Cap 151 of the Hong Kong Ordinances). The whole program involves 103 pre-school children with SEN and their parents. Prior to enrolling in this program, most of the children have been assessed to have autism, ADHD, or dyslexia. In this program, the Mullen Scales of Early Learning (Mullen, 1995) or Childhood Autism Rating Scale (Schopler, Reichler, DeVellis, & Daly, 1980) were administered to the children by counselling psychologists to measure their cognitive and motor abilities. In addition, their parents were also invited to participate in the survey interview of Vineland Adaptive Behavior Scales (Sparrow, Cicchetti, & Balla, 2008) and Child Behavior Checklist (Achenbach, 1991, 1992). Based on these measures and clinical observation, an Individualized Development Plan (IDP) has been designed for each child. A functional approach, rather than a diagnostic approach, has been applied in designing the IDPs, communicating them to the parents, and providing the children with relevant individual and group counselling and therapeutic services. Through illustration of this approach, we hope to stimulate further clinical and public discussion in the arenas of issues faced by children with SEN and their parents, as well as the perceived and projected advantages of early diagnosis and early intervention.

Breast reconstruction after mastectomy in the treatment of locally advanced breast cancer is often done in stages and before radiotherapy. We have previously published an algorithm for immediate free autologous reconstruction after neoadjuvant chemotherapy and preoperative radiotherapy. This protocol was designed to provide a shorter and simpler reconstructive path whilst improving cosmesis and maintaining oncological efficiency.A total of 29 patients were included and underwent surgery for 30 cancers by the first author between 2010 and September 2015. Data were prospectively entered into a database and analysed for tumour size, chemotherapeutic response, lymph node involvement, surgical complications and tumour recurrence.The mean age was 55 ± 7 years. Eighty percent of patients had either a partial or complete chemotherapeutic response defined as25% decrease in tumour size. Twenty-eight patients had free abdominal tissue transfer. One patient was excluded due to advanced disease. There were no take-backs due to microsurgical issues. One patient was reoperated on for a haematoma. Four patients had recurrent cancer during follow-up, three of whom are deceased.Many, but not all, breast reconstructive surgeons consider autologous reconstruction as the 'gold' standard in the presence of radiotherapy. Rearranging the order of radiotherapy and surgery means operating in a recently irradiated field. We believe the surgical challenges are outweighed by a shorter and simpler reconstructive journey that additionally results in a better cosmesis. It is possible to perform immediate free autologous reconstruction after neoadjuvant chemotherapy and preoperative radiotherapy with excellent results and at least equivalent oncological efficacy.

BACKGROUND: Current guidelines recommend offering genetic testing for Lynch syndrome to individuals whose tumors suggest this condition and to relatives of affected individuals. Little is known, however, regarding how patients view the prospect of such testing. In addition, data on preferences (utilities) for the potential outcomes of testing decisions for use in cost-effectiveness analyses are lacking. METHODS: Time tradeoff utilities were elicited for 10 potential outcomes of Lynch syndrome testing decisions and 3 associated cancers from 70 participants, representing a range of knowledge about and experiences with Lynch syndrome. RESULTS: Highest mean utilities were assigned to scenarios in which only the assessor's sibling had Lynch-associated colorectal cancer (ranging from 0.669 ± 0.231 to 0.760 ± 0.220). Utilities assigned to scenarios in which the assessor had Lynch-associated colorectal cancer ranged from 0.605 ± 0.252 to 0.682 ± 0.246, whereas the lowest mean utilities were assigned to 2 of the general cancer states (0.601 ± 0.238 and 0.593 ± 0.272 for colorectal and ovarian cancer respectively). Only 43% of the sample assigned higher values to undergoing Lynch testing and receiving negative results versus forgoing Lynch testing, whereas 50% assigned higher values to undergoing rather than forgoing surgery to prevent a subsequent cancer. CONCLUSIONS: Genetic testing for Lynch syndrome, regardless of results, can have profound effects on quality of life; the utilities we collected can be used to incorporate these effects into cost-effectiveness analyses. Importantly, preferences for the potential outcomes of testing vary substantially, calling into question the extent to which patients would avail themselves of such testing if it were offered to them. Cancer 2013. © 2012 American Cancer Society

Hyperkyphosis, an excessive anterior curvature in the thoracic spine, is associated with reduced health status in older adults. Hyperkyphosis is highly prevalent, more common in older women than men. There is no standard intervention to reduce age-related hyperkyphosis. Sex differences in response to a targeted intervention are not known.

Objectives. We assessed whether state Medicaid preferred drug lists are concordant with the World Health Organization's 2009 16th Essential Medicines List and with each other. We also characterized listed medicines by generic availability and appearance on treatment guidelines. Methods. We derived generic availability and first-line treatment status from the US Food and Drug Administration's Orange Book and the 2004–2009 National Health Service National Institute for Clinical Excellence guidelines. We report characteristics of Essential Medicines List and preferred drug list (PDL)-only medicines and describe differences between medicines that are frequently and infrequently listed on PDLs. Results. Only 6 of 120 Essential Medicines List medicines appeared on fewer than 50% of PDLs. PDL-only medicines (n = 249) were less likely than were Essential Medicines List medicines (n = 120) to have generic versions available (56% vs 76%) and to be first-line treatments (21% vs 41%). The content of PDLs was variable: 33% of medicines appeared on 80% to 100% of PDLs. Conclusions. Application of the essential medicines concept to Medicaid PDLs could reduce costs and provide more equitable and evidence-based health care to low-income patients in the United States.

Purpose: This randomized phase II study evaluated ASA404 (vadimezan; 5,6-dimethylxanthenone-4-acetic acid) in combination with docetaxel in castration-refractory metastatic prostate cancer (CRMPC). Experimental Design: Seventy-four patients with histopathologically confirmed CRMPC previously untreated with chemotherapy were randomized to receive either ≤10 cycles of docetaxel 75 mg/m2 alone (D; n = 39) or docetaxel plus ASA404 1,200 mg/m2 (A-D; n = 35). Study endpoints included prostate-specific antigen response, tumor response, median time to tumor progression, median survival, and toxicity. Results: The overall pattern of adverse events was similar in the two groups; however, there was a higher incidence of cardiac adverse events and neutropenia in the A-D group. Coadministration of ASA404 with docetaxel did not affect total systemic exposure of either drug. A higher prostate-specific antigen response rate was reported with A-D versus D (59.4% versus 36.8%), together with a larger median percentage reduction in prostate-specific antigen (84.0% versus 61.9%) and a shorter median time to prostate-specific antigen nadir (105 versus 119 d). Tumor response rate was 23.1% with A-D and 9.1% with D. Time to tumor progression and median survival were similar in the groups (time to tumor progression, 8.7 mo for A-D and 8.4 mo for D; survival, 17.0 mo for A-D and 17.2 mo for D). Hazard ratios for time to tumor progression and survival were 0.81 and 0.80, respectively, favoring A-D; 2-year survival was 33.3% with A-D and 22.8% with D. Conclusion: The study met some endpoints (prostate-specific antigen response, tumor response) but not others (i.e., time to tumor progression). The results indicate that the combination of ASA404 with docetaxel has acceptable toxicity, lacks adverse pharmacokinetic interaction, and, overall, has activity in CRMPC. Clin Cancer Res; 16(10); 2906–14. ©2010 AACR.

We constructed linear covalently closed (LCC) DNA minivectors as a non-viral gene-delivery vector alternative produced via a simple platform in vivo. DNA ministrings possess a heightened safety profile and also efficiently deliver DNA cargo to targeted cells. Conventional DNA vectors carry undesirable prokaryotic sequences, including antibiotic resistance genes, CpG motifs, and bacterial origins of replication, which may lead to the stimulation of host immunological responses. The bioavailability of conventional DNA vectors is also compromised due to their larger molecular size. Their circular nature may also impart chromosomal integration, leading to insertional mutagenesis. Bacterial sequences are excised from DNA minivectors, leaving only the gene of interest (GOI) and necessary eukaryotic expression elements. Our LCC DNA minivectors, or DNA ministrings, are devoid of immunogenic bacterial sequences; therefore improving their bioavailability and GOI expression. In the event of vector integration into the chromosome, the LCC DNA ministring will lethally disrupt the host chromosome, thereby removing the potentially dangerous mutant from the proliferating cell population. Consequently, DNA ministrings offer the benefits of 'minicircle' DNA while eliminating the potential for undesirable vector integration events. In comparison to conventional plasmids and their isogenic circular covalently closed (CCC) counterparts, DNA ministrings demonstrate superior bioavailability, transfection efficiency, and cytoplasmic kinetics - they thus require lower amounts of cationic surfactants for effective transfection of target cells. We have constructed a one-step inducible in vivo system for the production of DNA ministrings in Escherichia coli that is simple to use, rapid, and scalable.

While the natural hosts for bacteriophages are bacteria, there is growing evidence for the ability of phage to interact with mammalian cells, particularly with those of the human immune system. These interactions typically encompass two main features: (i) phage immunogenicity, or ability of phages to induce specific immune responses; and (ii) phage immunomodulation, which can be defined as the ability of phages to modify the immune system in both innate and adaptive responses. The aim of this chapter is to explore the interactions between phages and the immune system, and more specifically the implications of these interactions in the development of novel medical applications.

Bacteriophages (phages) offer many potential and existing applications to biotechnology, including their modification and use as protein/gene carriers. Phages possess many intrinsic physicochemical attributes that make them excellent candidates for use in gene therapy. In this chapter we will explore how phages have been employed in gene delivery as well as their future utility in this exciting medical application.

Tutorial assessment in PBL is thought to be a valid assessment approach and is believed to exert a positive impact on the learning process. Reports, however, have demonstrated that assessment by the facilitator can be unreliable. Training of faculty to conduct this type of assessment has tended to be lacking and is a likely contributor to this inconsistency. This report describes the final in a series of foundation-building faculty development workshops focused on the instructional methodology of PBL. The PBL Assessment and Feedback workshop reported here introduced the theory and practice of conducting process-based assessment accompanied by formative feedback. Scenario-based discussions, mock group demonstration, role-modeling, and role-play were utilized as adult learning-appropriate strategies to familiarize participants with process-based assessment and feedback. Evaluation of the workshop by participants provided evidence that the majority of participants were satisfied with the methods and content of the workshop. Suggestions for additional training in these assessment methods included additional examples, practice, workshops, or observation and mentoring.

In this study, we examined the relationship between students’ problem-based learning (PBL) skills and their content acquisition as measured by traditional examinations. We conducted this investigation to evaluate the assumption that students’ learning in the small group setting of PBL as evaluated by their faculty facilitators was an accurate indicator of students’ learning as measured by problem analysis tests and traditional content acquisition tests. Parallel model reliability analyses were conducted to determine reliability for each year’s assessment components, which included multiple choice examinations, image-based computer tests, facilitators’ evaluations of students’ performance in the PBL small groups, and assessments that measured the students’ problem analysis and problem-solving skills. We also performed correlation tests to analyze the data. The reliability tests show that all assessment measures were consistently significant. There were predominantly significant correlations between process type assessment measures and the more traditional objective tests. When analyzed on a yearly basis, all of the correlations were significant. When analyzed on a trimester basis, all of the correlations were positive, with many being significant. The finding that the process grade revealed significant correlation with the other two assessment tools indicates that although process type evaluations may seem to be primarily subjective, they are an important metric for monitoring student progress.

This report describes the first in a series of foundation-building faculty development workshops focused on the instructional methodology of problem-based learning (PBL). The PBL Process workshop reported here introduced the learning theory topics supporting PBL and utilized an extended roleplay method to provide participants with personal experience with the PBL learning cycle. Overall, participants were satisfied with the methods and content of the workshop. A majority of survey respondents indicated that simulating a complete iteration of the PBL process was an effective way to learn about PBL. Participants expressed relatively greater difficulty understanding and performing activities related to qualitative assessment of learning processes. The workshop was developed to align with adult learning principles, and continued refinement of the workshop has enhanced the learning theory components underpinning PBL as well as the experiential aspects. These dual goals have resulted in blending the existing experiential workshop with an online distance-learning component addressing the learning theory topics relevant to PBL pedagogy.

Palliative chemotherapy has an increasing role in the management of recurrent high-grade gliomas. Temozolomide is a well-tolerated agent that results in objective responses and stabilisation of disease. Theoretically, temozolomide may be more effective when given in a prolonged schedule rather than the standard 5 days-monthly schedule. This Phase II study examined the efficacy and toxicity of temozolomide when given in a two-weekly schedule. Twenty-five patients received 150 mg/m2 temozolomide daily for seven days alternating with seven days of no treatment. One cycle of temozolomide was a total of two weeks treatment in every 28 days. Of the 25 evaluable patients, there was one complete response (4%), four partial responses (16%) and 10 patients had disease stablisation (40%). The progression free survival at 6 months was 56%. Two-weekly temozolomide was well tolerated with only four episodes of Grade 3 thrombocytopenia. Overall, two-weekly temozolomide is an active and well tolerated schedule, but does not appear to improve on the activity of temozolomide using the standard 5-day schedule.

PurposeTo describe the process of building partnerships between a health professional group (university‐based researchers and organizations from within and outside the health sector) and the black communities, highlight the accomplishments and identify problems in the process.Design/methodology/approachThe description of the process of building partnerships with four black communities in Nova Scotia is organized in the following sections: the impetus for launching a Diabetes Primary Prevention for the Black Communities Project, its preparation, implementation, and evaluation. The accomplishments and the problems associated with the Project are analysed.FindingsRecruitment of participants for the focus groups was challenging. Response rate to survey questionnaire was moderate. Presentation of the Project results by one of the black Project assistants to the participant communities was well received. The Project was quite successful in encouraging community involvement by engaging community groups in several small‐scale activities. Three issues related to project implementation were identified: recruitment of focus groups, participant disappointment, and survey return rates. Strategies incorporating the principles of involving a target audience, providing a service, empowering people and respecting cultural diversity with the aim to ensure successful partnership building with the black communities were proposed.Originality/valueThis paper describes the process of forging partnership with the black communities. The results of the Project could serve as a paradigm for developing culturally sensitive and responsive strategies to lessen the burden of type 2 diabetes in other racial minority communities.

This paper reviews the epidemiology, pathophysiology and clinical significance of isolated systolic hypertension (ISH) in the elderly. Aging is associated with structural and functional changes in the arterial tree. Intimal thickening, migration of small muscle cells to the intima, medial fibrosis, and elastic fiber degeneration result in increased arterial stiffness and ISH. The augmented systemic vascular resistance in the elderly is mediated by increased arterial stiffness. Aging is correlated with overactivity of the sympathetic nervous system, reduced neuronal plasma norepinephrine uptake, and baroreceptor dysfunction. These functional changes all contribute to the development of ISH in elderly persons. Prospective and epidemiological studies have demonstrated that ISH is associated with coronary and cerebrovascular morbidity and mortality. There is good evidence indicating that lifestyle modifications such as weight reduction, increased physical activity, moderation of dietary sodium, and decreased alcohol intake, in combination with pharmacological therapy can effectively reduce blood pressure in elderly individuals with ISH. Primary health care providers can make significant contributions to the care of elderly persons with ISH. These contributions involve educating elderly people to control hypertension through lifestyle modification, monitoring the efficacy of antihypertensive therapy, and preventing complications associated with non-compliance with therapeutic regimens.

Observational and interventional studies that evaluate the impact of hormone replacement therapy (HRT) on cardiovascular changes have produced inconsistent and inconclusive results. The present study sought to elucidate the influence of HRT on aortic distensibility, left ventricular mass (LVM) and 24-h blood pressure (BP) profile in 38 menopausal women who were either HRT users or non-users. The two groups were similar for age, ambulatory BP, aortic distensibility, cardiac mass, lipid profile and body mass index but differed in clinic diastolic BP (DBP). HRT non-dippers had significantly lower clinic and daytime DBP and a smaller nocturnal BP reduction than dippers. Daytime DBP was significantly and inversely related to duration of HRT use. The present study demonstrates that hormonal therapy after menopause lowers DBP, but shows no significant influence on aortic distensibility, cardiac mass or 24-h BP profile. HRT users who were dippers demonstrated a significantly greater nocturnal BP reduction. Long-term controlled trails are needed to better define the effects of estrogen and progestin on the aorta, the heart and 24-h BP profile in normotensive and hypertensive menopausal women.

The authors examine the impact of consumer involvement on consumers'willingness to engage in relationships with service providers, because healthy relationships between consumers and service providers depend on the voluntary participation of consumers in relationships. They also examine the effect that involvement has on consumers' expectations of relational efforts by the service provider. On the basis of survey results from the telecom and health sector, the authors' results indicate that more involved consumers express greater interest in engaging in relationships with service providers. Also, although high-involvement customers do not differ from their low-involvement counterparts in terms of their expectations that their service providers communicate with them regularly and be price-competitive, they express a greater desire for fairness in treatment and being involved in solutions to their problems. These results indicate that the opportunity exists to engage high-involvement customers in long-term relationship programs tailored to their unique needs.

There is a dearth of information on the cardiovascular health of immigrant women. The present study analyzed the dataset from the National Population Health Survey to describe the modifiable CVD risk factors of Canadian immigrant women. Results indicated a statistically significant difference in modifiable CVD risk factors with respect to the country of birth, spoken language, and the length of time in Canada. The prevalence of smoking was significantly different across all income groups, with the lowest and middle income groups having the highest prevalence rate. Compared with their non‐white counterparts, the white immigrant women had a greater prevalence of obesity, hypertension, and smoking. Irrespective of race and country of birth, immigrant women tended to have worse CVD risk factors than non‐immigrant women. Age was the most important predictor of heart disease and hypertension. Implications of the study results for evidence‐based practice are discussed.