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

Setting upper limits on the strength of periodic gravitational waves from PSR J1939+2134 using the first science data from the GEO 600 and LIGO detectors

Data collected by the GEO 600 and LIGO interferometric gravitational wave detectors during their first observational science run were searched for continuous gravitational waves from the pulsar J1939+2134 at twice its rotation frequency. Two independent analysis methods were used and are demonstrated in this paper: a frequency domain method and a time domain method. Both achieve consistent null results, placing new upper limits on the strength of the pulsar's gravitational wave emission. A model emission mechanism is used to interpret the limits as a constraint on the pulsar's equatorial ellipticity

First upper limits from LIGO on gravitational wave bursts

We report on a search for gravitational wave bursts using data from the first science run of the LIGO detectors. Our search focuses on bursts with durations ranging from 4 ms to 100 ms, and with significant power in the LIGO sensitivity band of 150 to 3000 Hz. We bound the rate for such detected bursts at less than 1.6 events per day at 90% confidence level. This result is interpreted in terms of the detection efficiency for ad hoc waveforms (Gaussians and sine-Gaussians) as a function of their root-sum-square strain h_{rss}; typical sensitivities lie in the range h_{rss} ~ 10^{-19} - 10^{-17} strain/rtHz, depending on waveform. We discuss improvements in the search method that will be applied to future science data from LIGO and other gravitational wave detectors.Comment: 21 pages, 15 figures, accepted by Phys Rev D. Fixed a few small typos and updated a few reference

Analysis of LIGO data for gravitational waves from binary neutron stars

We report on a search for gravitational waves from coalescing compact binary systems in the Milky Way and the Magellanic Clouds. The analysis uses data taken by two of the three LIGO interferometers during the first LIGO science run and illustrates a method of setting upper limits on inspiral event rates using interferometer data. The analysis pipeline is described with particular attention to data selection and coincidence between the two interferometers. We establish an observational upper limit of $\mathcal{R}<$1.7 \times 10^{2}$per year per Milky Way Equivalent Galaxy (MWEG), with 90coalescence rate of binary systems in which each component has a mass in the range 1--3$M_\odot$.Comment: 17 pages, 9 figure

Broad phenotypic spectrum in familial adenomatous polyposis; from early onset and severe phenotypes to late onset of attenuated polyposis with the first manifestation at age 72

<p>Abstract</p> <p>Background</p> <p>Familial adenomatous polyposis (FAP) is typically characterized by multiple colonic polyps and frequent extracolonic features. Whereas the number of colonic polyps has been linked to the <it>APC </it>gene mutation, possible genotype-phenotype correlations largely remain to be defined for the extracolonic manifestations.</p> <p>Methods</p> <p>Full genomic sequencing combined with multiplex ligation-dependent probe amplification was used to identify <it>APC </it>gene mutations, which were correlated to the clinical presentations.</p> <p>Results</p> <p>10 novel <it>APC </it>gene mutations were identified in 11 families. A broad spectrum of extracolonic manifestations was identified in most of these individuals. Two sisters with an insertion in codon 528 (c.1582_1583insGC) both showed severe phenotypes with classical polyposis, upper gastrointestinal polyps and thyroid cancer. A woman with a 3'<it>APC </it>mutation (c.5030_5031insAA) developed colon cancer at age 72 as the first manifestation of attenuated FAP.</p> <p>Conclusion</p> <p>With an increasing number of FAP families diagnosed, a broad and variable tumor spectrum and a high frequency of extracolonic manifestations are gradually recognized. We report novel <it>APC </it>mutations and present two FAP cases that suggest familial aggregation of thyroid cancer and demonstrate the need to consider attenuated FAP also among elderly patients with colon cancer.</p

Improving the sensitivity to gravitational-wave sources by modifying the input-output optics of advanced interferometers

We study frequency dependent (FD) input-output schemes for signal-recycling interferometers, the baseline design of Advanced LIGO and the current configuration of GEO 600. Complementary to a recent proposal by Harms et al. to use FD input squeezing and ordinary homodyne detection, we explore a scheme which uses ordinary squeezed vacuum, but FD readout. Both schemes, which are sub-optimal among all possible input-output schemes, provide a global noise suppression by the power squeeze factor, while being realizable by using detuned Fabry-Perot cavities as input/output filters. At high frequencies, the two schemes are shown to be equivalent, while at low frequencies our scheme gives better performance than that of Harms et al., and is nearly fully optimal. We then study the sensitivity improvement achievable by these schemes in Advanced LIGO era (with 30-m filter cavities and current estimates of filter-mirror losses and thermal noise), for neutron star binary inspirals, and for narrowband GW sources such as low-mass X-ray binaries and known radio pulsars. Optical losses are shown to be a major obstacle for the actual implementation of these techniques in Advanced LIGO. On time scales of third-generation interferometers, like EURO/LIGO-III (~2012), with kilometer-scale filter cavities, a signal-recycling interferometer with the FD readout scheme explored in this paper can have performances comparable to existing proposals. [abridged]Comment: Figs. 9 and 12 corrected; Appendix added for narrowband data analysi

Detector Description and Performance for the First Coincidence Observations between LIGO and GEO

For 17 days in August and September 2002, the LIGO and GEO interferometer gravitational wave detectors were operated in coincidence to produce their first data for scientific analysis. Although the detectors were still far from their design sensitivity levels, the data can be used to place better upper limits on the flux of gravitational waves incident on the earth than previous direct measurements. This paper describes the instruments and the data in some detail, as a companion to analysis papers based on the first data.Comment: 41 pages, 9 figures 17 Sept 03: author list amended, minor editorial change