Dynamical Boson Stars

The idea of stable, localized bundles of energy has strong appeal as a model for particles. In the 1950s John Wheeler envisioned such bundles as smooth configurations of electromagnetic energy that he called {\em geons}, but none were found. Instead, particle-like solutions were found in the late 1960s with the addition of a scalar field, and these were given the name {\em boson stars}. Since then, boson stars find use in a wide variety of models as sources of dark matter, as black hole mimickers, in simple models of binary systems, and as a tool in finding black holes in higher dimensions with only a single killing vector. We discuss important varieties of boson stars, their dynamic properties, and some of their uses, concentrating on recent efforts.Comment: 79 pages, 25 figures, invited review for Living Reviews in Relativity; major revision in 201

Prevalence of the most frequent BRCA1 mutations in Polish population

The purpose of our study was to establish the frequency and distribution of the four most common BRCA1 mutations in Polish general population and in a series of breast cancer patients. Analysis of the population frequency of 5382insC (c.5266dupC), 300T >G (p.181T >G), 185delAG (c.68_69delAG) and 3819del5 (c.3700_3704del5) mutations of the BRCA1 gene were performed on a group of respectively 16,849, 13,462, 12,485 and 3923 anonymous samples collected at birth in seven Polish provinces. The patient group consisted of 1845 consecutive female breast cancer cases. The most frequent BRCA1 mutation in the general population was 5382insC found in 29 out of 16,849 samples (0.17%). 300T >G and 3819del5 mutations were found in respectively 11 of 13,462 (0.08%) and four of 3923 (0.1%) samples. The population prevalence for combined Polish founder 5382insC and 300T >G mutations was 0.25% (1/400). The frequencies of 5382insC and 300T >G carriers among consecutive breast cancer cases were, respectively, 1.9% (35/1845) and 1.2% (18/1486). Comparing these data with the population frequency, we calculated the relative risk of breast cancer for 5382insC mutation at OR = 17 and for 300T >G mutation at OR = 26. Our results, based on large population studies, show high frequencies of founder 5382insC and 300T >G BRCA1 mutations in Polish general population. Carriage of one of these mutations is connected with a very high relative risk of breast cancer

Physician Perception of Blood Pressure Control and Treatment Behavior in High-Risk Hypertensive Patients: A Cross-Sectional Study

Objective: We examined physician perception of blood pressure control and treatment behavior in patients with previous cardiovascular disease and uncontrolled hypertension as defined by European Guidelines. Methods: A cross-sectional study was conducted in which 321 primary care physicians throughout Spain consecutively studied 1,614 patients aged ≥18 years who had been diagnosed and treated for hypertension (blood pressure ≥140/90 mmHg), and had suffered a documented cardiovascular event. The mean value of three blood pressure measurements taken using standardized procedures was used for statistical analysis. Results: Mean blood pressure was 143.4/84.9 mmHg, and only 11.6% of these cardiovascular patients were controlled according to 2007 European Guidelines for Hypertension Management target of <130/80 mmHg. In 702 (49.2%) of the 1426 uncontrolled patients, antihypertensive medication was not changed, and in 480 (68.4%) of these cases this was due to the physicianś judgment that blood pressure was adequately controlled. In 320 (66.7%) of the latter patients, blood pressure was 130-139/80-89 mmHg. Blood pressure level was the main factor associated (inversely) with no change in treatment due to physician perception of adequate control, irrespective of sociodemographic and clinical factors. Conclusions: Physicians do not change antihypertensive treatment in many uncontrolled cardiovascular patients because they considered it unnecessary, especially when the BP values are only slightly above the guideline target. It is possible that the guidelines may be correct, but there is also the possibility that the care by the physicians is appropriate since BP <130/80 mmHg is hard to achieve, and recent reviews suggest there is insufficient evidence to support such a low BP targetFunding for this study was obtained from RECORDATI ESPAÑA, S.L through an unrestricted grant. Krista Lundelin has a ‘‘Rio Hortega’’ research training contract (Expediente CM10/00327) from the Ministry of Science and Innovation (Instituto de Salud Carlos III), Spain Governmen

Log odds of carrying an Ancestral Mutation in BRCA1 or BRCA2 for a Defined personal and family history in an Ashkenazi Jewish woman (LAMBDA)

INTRODUCTION: Ancestral mutations in BRCA1 and BRCA2 are common in people of Ashkenazi Jewish descent and are associated with a substantially increased risk of breast and ovarian cancer. Women considering mutation testing usually have several personal and family cancer characteristics, so predicting mutation status from one factor alone could be misleading. The aim of this study was to develop a simple algorithm to estimate the probability that an Ashkenazi Jewish woman carries an ancestral mutation, based on multiple predictive factors. METHODS: We studied Ashkenazi Jewish women with a personal or family history of breast or ovarian cancer and living in Melbourne or Sydney, Australia, or with a previous diagnosis of breast or ovarian cancer and living in the UK. DNA samples were tested for the germline mutations 185delAG and 5382insC in BRCA1, and 6174delT in BRCA2. Logistic regression was used to identify, and to estimate the predictive strength of, major determinants. RESULTS: A mutation was detected in 64 of 424 women. An algorithm was developed by combining our findings with those from similar analyses of a large study of unaffected Jewish women in Washington. Starting with a baseline score, a multiple of 0.5 (based on the logistic regression estimates) is added for each predictive feature. The sum is the estimated log odds ratio that a woman is a carrier, and is converted to a probability by using a table. There was good internal consistency. CONCLUSIONS: This simple algorithm might be useful in the clinical and genetic counselling setting. Comparison and validation in other settings should be sought

Variation in breast cancer risk in BRCA1 and BRCA2 mutation carriers

Genetic testing for BRCA1 and BRCA2 (BRCA1/2) mutations can provide important information for women who are concerned about their breast and ovarian cancer risks and need to make relevant prevention and medical management decisions. However, lifetime risks of breast cancer in individual BRCA1/2 mutation carriers have been confusing to apply in clinical decision-making. Published risk estimates vary significantly and are very dependent on the characteristics of the population under study. Recently, Begg and colleagues estimated cancer risks in a population-based study of BRCA1/2 mutation carriers. Here, we discuss the clinical decision-making implications of this research in the context of risk factors that may influence risk estimates in BRCA1/2 mutation carriers

A discrete choice experiment of preferences for genetic counselling among Jewish women seeking cancer genetics services

To determine which aspects of breast cancer genetic counselling are important to Ashkenazi Jewish women, a discrete choice experiment was conducted. Participants consisted of 339 Australian Ashkenazi Jewish women who provided a blood sample for research used to test for Ashkenazi Jewish ancestral mutations in the genes BRCA1 and BRCA2, and were offered their genetic test result through a cancer genetics service. Main outcome measures were women's preferences for, and trade-offs between, the genetic counselling aspects of providing cancer, gene, and risk information (information); giving advice about cancer surveillance (surveillance); preparing for genetic testing (preparation); and, assistance with decision-making (direction). Respondents most valued information, about twice as much as advice about surveillance, four times as much as preparation for testing, and nine times as much as assistance with decision-making, which was least valued. Women's preferences were consistent with the major goals of genetic counselling, which include providing information and surveillance advice, and avoiding direction by facilitating autonomous decision-making. There were differences between the women in which aspects they most favoured, suggesting that counselling that elicits and responds to clients' preferences is more likely to meet clients' needs

The Ontario printed educational message (OPEM) trial to narrow the evidence-practice gap with respect to prescribing practices of general and family physicians: a cluster randomized controlled trial, targeting the care of individuals with diabetes and hypertension in Ontario, Canada

<p>Abstract</p> <p>Background</p> <p>There are gaps between what family practitioners do in clinical practice and the evidence-based ideal. The most commonly used strategy to narrow these gaps is the printed educational message (PEM); however, the attributes of successful printed educational messages and their overall effectiveness in changing physician practice are not clear. The current endeavor aims to determine whether such messages change prescribing quality in primary care practice, and whether these effects differ with the format of the message.</p> <p>Methods/design</p> <p>The design is a large, simple, factorial, unblinded cluster-randomized controlled trial. PEMs will be distributed with <b><it>informed</it></b>, a quarterly evidence-based synopsis of current clinical information produced by the Institute for Clinical Evaluative Sciences, Toronto, Canada, and will be sent to all eligible general and family practitioners in Ontario. There will be three replicates of the trial, with three different educational messages, each aimed at narrowing a specific evidence-practice gap as follows: 1) angiotensin-converting enzyme inhibitors, hypertension treatment, and cholesterol lowering agents for diabetes; 2) retinal screening for diabetes; and 3) diuretics for hypertension.</p> <p>For each of the three replicates there will be three intervention groups. The first group will receive <b><it>informed </it></b>with an attached postcard-sized, short, directive "outsert." The second intervention group will receive <b><it>informed </it></b>with a two-page explanatory "insert" on the same topic. The third intervention group will receive <b><it>informed</it></b>, with both the above-mentioned outsert and insert. The control group will receive <b><it>informed </it></b>only, without either an outsert or insert.</p> <p>Routinely collected physician billing, prescription, and hospital data found in Ontario's administrative databases will be used to monitor pre-defined prescribing changes relevant and specific to each replicate, following delivery of the educational messages. Multi-level modeling will be used to study patterns in physician-prescribing quality over four quarters, before and after each of the three interventions. Subgroup analyses will be performed to assess the association between the characteristics of the physician's place of practice and target behaviours.</p> <p>A further analysis of the immediate and delayed impacts of the PEMs will be performed using time-series analysis and interventional, auto-regressive, integrated moving average modeling.</p> <p>Trial registration number</p> <p>Current controlled trial ISRCTN72772651.</p

Structural Constraints Identified with Covariation Analysis in Ribosomal RNA

Covariation analysis is used to identify those positions with similar patterns of sequence variation in an alignment of RNA sequences. These constraints on the evolution of two positions are usually associated with a base pair in a helix. While mutual information (MI) has been used to accurately predict an RNA secondary structure and a few of its tertiary interactions, early studies revealed that phylogenetic event counting methods are more sensitive and provide extra confidence in the prediction of base pairs. We developed a novel and powerful phylogenetic events counting method (PEC) for quantifying positional covariation with the Gutell lab’s new RNA Comparative Analysis Database (rCAD). The PEC and MI-based methods each identify unique base pairs, and jointly identify many other base pairs. In total, both methods in combination with an N-best and helix-extension strategy identify the maximal number of base pairs. While covariation methods have effectively and accurately predicted RNAs secondary structure, only a few tertiary structure base pairs have been identified. Analysis presented herein and at the Gutell lab’s Comparative RNA Web (CRW) Site reveal that the majority of these latter base pairs do not covary with one another. However, covariation analysis does reveal a weaker although significant covariation between sets of nucleotides that are in proximity in the three-dimensional RNA structure. This reveals that covariation analysis identifies other types of structural constraints beyond the two nucleotides that form a base pair