Novel mutations in the BRCA1 and BRCA2 genes in Iranian women with early-onset breast cancer

BACKGROUND: Breast cancer is the most common female malignancy and a major cause of death in middle-aged women. So far, germline mutations in the BRCA1 and BRCA2 genes in patients with early-onset breast and/or ovarian cancer have not been identified within the Iranian population. METHODS: With the collaboration of two main centres for cancer in Iran, we obtained clinical information, family history and peripheral blood from 83 women under the age of 45 with early-onset breast cancer for scanning of germline mutations in the BRCA1 and BRCA2 genes. We analysed BRCA1 exons 11 and BRCA2 exons 10 and 11 by the protein truncation test, and BRCA1 exons 2, 3, 5, 13 and 20 and BRCA2 exons 9, 17, 18 and 23 with the single-strand conformation polymorphism assay on genomic DNA amplified by polymerase chain reaction. RESULTS: Ten sequence variants were identified: five frameshifts (putative mutations – four novel); three missense changes of unknown significance and two polymorphisms, one seen commonly in both Iranian and British populations. CONCLUSIONS Identification of these novel mutations suggests that any given population should develop a mutation database for its programme of breast cancer screening. The pattern of mutations seen in the BRCA genes seems not to differ from other populations studied. Early-onset breast cancer (less than 45 years) and a limited family history is sufficient to justify mutation screening with a detection rate of over 25% in this group, whereas sporadic early-onset breast cancer (detection rate less than 5%) is unlikely to be cost-effective

Photon rockets and gravitational radiation

The absence of gravitational radiation in Kinnersley's ``photon rocket'' solution of Einstein's equations is clarified by studying the mathematically well-defined problem of point-like photon rockets in Minkowski space (i.e. massive particles emitting null fluid anisotro\-pically and accelerating because of the recoil). We explicitly compute the (uniquely defined) {\it linearized} retarded gravitational waves emitted by such objects, which are the coherent superposition of the gravitational waves generated by the motion of the massive point-like rocket and of those generated by the energy-momentum distribution of the photon fluid. In the special case (corresponding to Kinnersley's solution) where the anisotropy of the photon emission is purely dipolar we find that the gravitational wave amplitude generated by the energy-momentum of the photons exactly cancels the usual $1/r$ gravitational wave amplitude generated by the accelerated motion of the rocket. More general photon anisotropies would, however, generate genuine gravitational radiation at infinity. Our explicit calculations show the compatibility between the non-radiative character of Kinnersley's solution and the currently used gravitational wave generation formalisms based on post-Minkowskian perturbation theory.Comment: 21 pages, LATEX, submitted to Class. Quant. Gra

BlindBuilder : a new encoding to evolve Lego-like structures

This paper introduces a new representation for assemblies of small Lego-like elements: structures are indirectly encoded as construction plans. This representation shows some interesting properties such as hierarchy, modularity and easy constructibility checking by definition. Together with this representation, efficient GP operators are introduced that allow efficient and fast evolution, as witnessed by the results on two construction problems that demonstrate that the proposed approach is able to achieve both compactness and reusability of evolved components

High resolution radio observations of the colliding-wind binary WR140

Milli-arcsecond resolution Very Long Baseline Array (VLBA) observations of the archetype WR+O star colliding-wind binary (CWB) system WR140 are presented for 23 epochs between orbital phases 0.74 and 0.97. At 8.4 GHz, the emission in the wind-collision region (WCR) is clearly resolved as a bow-shaped arc that rotates as the orbit progresses. We interpret this rotation as due to the O star moving from SE to approximately E of the WR star, which leads to solutions for the orbit inclination of 122+/-5 deg, the longitude of the ascending node of 353+/-3 deg, and an orbit semi-major axis of 9.0+/-0.5 mas. The distance to WR140 is determined to be 1.85+/-0.16 kpc, which requires the O star to be a supergiant. The inclination implies the mass of the WR and O star to be 20+/-4 and 54+/-10 solar masses respectively. We determine a wind-momentum ratio of 0.22, with an expected half-opening angle for the WCR of 63 deg, consistent with 65+/-10 deg derived from the VLBA observations. Total flux measurements from Very Large Array (VLA) observations show the radio emission from WR140 is very closely the same from one orbit to the next, pointing strongly toward emission, absorption and cooling mechanism(s) that are controlled largely by the orbital motion. The synchrotron spectra evolve dramatically through the orbital phases observed, exhibiting both optically thin and optically thick emission. We discuss a number of absorption and cooling mechanisms that may determine the evolution of the synchrotron spectrum with orbital phase.Comment: Accepted by ApJ, to appear in v623, April 20, 2005. 14 pages, 13 figs, requires emulateapj.cls. A version with full resolution figs can be obtained from http://www.drao.nrc.ca/~smd/preprint/wr140_data.pd

Epidemics in Networks of Spatially Correlated Three-dimensional Root Branching Structures

Using digitized images of the three-dimensional, branching structures for root systems of bean seedlings, together with analytical and numerical methods that map a common 'SIR' epidemiological model onto the bond percolation problem, we show how the spatially-correlated branching structures of plant roots affect transmission efficiencies, and hence the invasion criterion, for a soil-borne pathogen as it spreads through ensembles of morphologically complex hosts. We conclude that the inherent heterogeneities in transmissibilities arising from correlations in the degrees of overlap between neighbouring plants, render a population of root systems less susceptible to epidemic invasion than a corresponding homogeneous system. Several components of morphological complexity are analysed that contribute to disorder and heterogeneities in transmissibility of infection. Anisotropy in root shape is shown to increase resilience to epidemic invasion, while increasing the degree of branching enhances the spread of epidemics in the population of roots. Some extension of the methods for other epidemiological systems are discussed.Comment: 21 pages, 8 figure

What difference does ("good") HRM make?

The importance of human resources management (HRM) to the success or failure of health system performance has, until recently, been generally overlooked. In recent years it has been increasingly recognised that getting HR policy and management "right" has to be at the core of any sustainable solution to health system performance. In comparison to the evidence base on health care reform-related issues of health system finance and appropriate purchaser/provider incentive structures, there is very limited information on the HRM dimension or its impact. Despite the limited, but growing, evidence base on the impact of HRM on organisational performance in other sectors, there have been relatively few attempts to assess the implications of this evidence for the health sector. This paper examines this broader evidence base on HRM in other sectors and examines some of the underlying issues related to "good" HRM in the health sector. The paper considers how human resource management (HRM) has been defined and evaluated in other sectors. Essentially there are two sub-themes: how have HRM interventions been defined? and how have the effects of these interventions been measured in order to identify which interventions are most effective? In other words, what is "good" HRM? The paper argues that it is not only the organisational context that differentiates the health sector from many other sectors, in terms of HRM. Many of the measures of organisational performance are also unique. "Performance" in the health sector can be fully assessed only by means of indicators that are sector-specific. These can focus on measures of clinical activity or workload (e.g. staff per occupied bed, or patient acuity measures), on measures of output (e.g. number of patients treated) or, less frequently, on measures of outcome (e.g. mortality rates or rate of post-surgery complications). The paper also stresses the need for a "fit" between the HRM approach and the organisational characteristics, context and priorities, and for recognition that so-called "bundles" of linked and coordinated HRM interventions will be more likely to achieve sustained improvements in organisational performance than single or uncoordinated interventions

Improved efficacy response attributed to diagnostic selection – Interim results of the phase 1 experience from ALKA-372-001

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Prospective Investigation of Markers of Elevated Delirium Risk (PRIMED Risk) study protocol: a prospective, observational cohort study investigating blood and cerebrospinal fluid biomarkers for delirium and cognitive dysfunction in older patients [version 1; peer review: awaiting peer review]

BACKGROUND: Delirium is a common post-operative complication, particularly in older adults undergoing major or emergency procedures. It is associated with increased length of intensive care and hospital stay, post-operative mortality and subsequent dementia risk. Current methods of predicting delirium incidence, duration and severity have limitations. Investigation of blood and cerebrospinal fluid (CSF) biomarkers linked to delirium may improve understanding of the underlying pathophysiology, particularly with regard to the extent this is shared or distinct with underlying dementia. Together, these have the potential for development of better risk stratification tools and perioperative interventions. / METHODS: 200 patients over the age of 70 scheduled for surgery with routine spinal anaesthetic will be recruited from UK hospitals. Their cognitive and functional baseline status will be assessed pre-operatively by telephone. Time-matched CSF and blood samples will be taken at the time of surgery and analysed for known biomarkers of neurodegeneration and neuroinflammation. Patients will be assessed daily for delirium until hospital discharge and will have regular cognitive follow-up for two years. Primary outcomes will be change in modified Telephone Interview for Cognitive Status (TICS-m) score at 12 months and rate of change of TICS-m score. Delirium severity, duration and biomarker levels will be treated as exposures in a random effects linear regression models. PRIMED Risk has received regulatory approvals from Health Research Authority and London – South East Research Ethics Committee. / DISCUSSION: The main anticipated output from this study will be the quantification of biomarkers of acute and chronic contributors to cognitive impairment after surgery. In addition, we aim to develop better risk prediction models for adverse cognitive outcomes