Attaining minimally disruptive medicine: context, challenges and a roadmap for implementation.

In this second of two papers on minimally disruptive medicine, we use the language of patient workload and patient capacity from the Cumulative Complexity Model to accomplish three tasks. First, we outline the current context in healthcare, comprised of contrasting problems: some people lack access to care and others receive too much care in an overmedicalised system, both of which reflect imbalances between patients' workloads and their capacity. Second, we identify and address five tensions and challenges between minimally disruptive medicine, the existing context, and other approaches to accessible and patient-centred care such as evidence-based medicine and greater patient engagement. Third, we outline a roadmap of three strategies toward implementing minimally disruptive medicine in practice, including large-scale paradigm shifts, mid-level add-ons to existing reform efforts, and a modular strategy using an existing 'toolkit' that is more limited in scope, but can fit into existing healthcare systems.

Hormone therapy for management of menopausal symptoms: understanding [corrected] breast cancer risk.

Since the publication of the Women's Health Initiative, women seeking relief from menopausal symptoms often express concerns about the risk of hormone therapy (HT). In women at increased risk for breast cancer or with a personal history of breast cancer, the decision to use HT for the treatment of menopausal symptoms must be carefully considered in the context of the most recent literature. It is well established that HT is the most effective treatment for climacteric symptoms and sexual dysfunction. The evidence to date on the use of HT in women with a history of breast cancer is complicated by the fact that the majority of breast cancers are estrogen responsive and the concern about risk of recurrence. Over the past decade, survival after breast cancer treatment has continued to improve resulting in millions of survivors worldwide. As a result of breast cancer therapies, the prevalence of menopausal symptoms is increasing in survivors, and both clinicians and patients are seeking safe and effective therapies for symptom management. This article will review the role of HT in the treatment of menopausal symptoms in women without breast cancer and those with a personal history of breast cancer or those who are at increased risk of breast cancer. Management of menopause-related symptoms will be reviewed with a focus on strategies to improve quality of life.

Modelling the determinants of 2000 m rowing ergometer performance: a proportional, curvilinear allometric approach.

Previous studies have investigated the determinants of indoor rowing using correlations and linear regression. However, the power demands of ergometer rowing are proportional to the cube of the flywheel's (and boat's) speed. A rower's speed, therefore, should be proportional to the cube root (0.33) of power expended. Hence, the purpose of the present study was to explore the relationship between 2000 m indoor rowing speed and various measures of power of 76 elite rowers using proportional, curvilinear allometric models. The best single predictor of 2000 m rowing ergometer performance was power at VO(2max)(WVO(2max))(0.28), that explained R(2)=95.3% in rowing speed. The model realistically describes the greater increment in power required to improve a rower's performance by the same amount at higher speeds compared with that at slower speeds. Furthermore, the fitted exponent, 0.28 (95% confidence interval 0.226-0.334) encompasses 0.33, supporting the assumption that rowing speed is proportional to the cube root of power expended. Despite an R(2)=95.3%, the initial model was unable to explain "sex" and "weight-class" differences in rowing performances. By incorporating anaerobic as well as aerobic determinants, the resulting curvilinear allometric model was common to all rowers, irrespective of sex and weight class.

RNA-binding properties of in vitro expressed histidine-tagged RB69 RegA translational repressor protein.

To facilitate RNA-binding studies of the phage RB69 RegA translational repressor protein, regA was configured to add six histidines to the carboxyl end of the protein. In vitro transcription-translation from the T7 promoter on plasmid pSA1 yielded a RegA69-His6 protein that binds nickel-Sepharose and elutes with 0.5 M imidazole. The system was further modified to avoid cloning and the toxic effects of RegA on Escherichia coli by the polymerase chain reaction (PCR), producing linear templates with the configuration T7 promoter-TIR-regA-His6. A translation initiation region was used that conforms to consensus E. coli and eukaryotic initiation sites and eliminates the target for RegA autogenous repression. RegA69-His6 synthesized in E. coli S30 or wheat germ extracts displayed RNA-binding properties similar to wild-type RB69 RegA. Specificity of RNA binding was demonstrated by in vitro repression of T4 gp44 and gp45 but not beta-lactamase, by differential binding to poly(U)- and poly(C)-agarose, and by site-specific binding to a 23-base gene 44 target RNA but not to mutant 44 RNA. Therefore, addition of the His6 tag to the C-terminus of RB69 RegA does not dramatically alter RNA binding, indicating that this region is not directly involved in site recognition. With access to several T4-like phage genomes and regA mutant sequences, in vitro synthesis of His-tagged proteins directly from linear PCR products provides a convenient and efficient system to study RegA and other interesting RNA-binding proteins.