Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies.

BACKGROUND: Half the epidemiological studies with information about menopausal hormone therapy and ovarian cancer risk remain unpublished, and some retrospective studies could have been biased by selective participation or recall. We aimed to assess with minimal bias the effects of hormone therapy on ovarian cancer risk. METHODS: Individual participant datasets from 52 epidemiological studies were analysed centrally. The principal analyses involved the prospective studies (with last hormone therapy use extrapolated forwards for up to 4 years). Sensitivity analyses included the retrospective studies. Adjusted Poisson regressions yielded relative risks (RRs) versus never-use. FINDINGS: During prospective follow-up, 12 110 postmenopausal women, 55% (6601) of whom had used hormone therapy, developed ovarian cancer. Among women last recorded as current users, risk was increased even with <5 years of use (RR 1·43, 95% CI 1·31-1·56; p<0·0001). Combining current-or-recent use (any duration, but stopped <5 years before diagnosis) resulted in an RR of 1·37 (95% CI 1·29-1·46; p<0·0001); this risk was similar in European and American prospective studies and for oestrogen-only and oestrogen-progestagen preparations, but differed across the four main tumour types (heterogeneity p<0·0001), being definitely increased only for the two most common types, serous (RR 1·53, 95% CI 1·40-1·66; p<0·0001) and endometrioid (1·42, 1·20-1·67; p<0·0001). Risk declined the longer ago use had ceased, although about 10 years after stopping long-duration hormone therapy use there was still an excess of serous or endometrioid tumours (RR 1·25, 95% CI 1·07-1·46, p=0·005). INTERPRETATION: The increased risk may well be largely or wholly causal; if it is, women who use hormone therapy for 5 years from around age 50 years have about one extra ovarian cancer per 1000 users and, if its prognosis is typical, about one extra ovarian cancer death per 1700 users. FUNDING: Medical Research Council, Cancer Research UK

Superweakly interacting dark matter from the Minimal Walking Technicolor

We study a superweakly interacting dark matter particle motivated by minimal walking technicolor theories. Our WIMP is a mixture of a sterile state and a state with the charges of a standard model fourth family neutrino. We show that the model can give the right amount of dark matter over a range of the WIMP mass and mixing angle. We compute bounds on the model parameters from the current accelerator data including the oblique corrections to the precision electroweak parameters, as well as from cryogenic experiments, Super-Kamiokande and from the IceCube experiment. We show that consistent dark matter solutions exist which satisfy all current constraints. However, almost the entire parameter range of the model lies within the the combined reach of the next generation experiments.Comment: 29 pages, 6 figure

Crosstalk between G-protein and Ca2+ pathways switches intracellular cAMP levels

Cyclic adenosine monophosphate and cyclic guanosine monophosphate are universal intracellular messengers whose concentrations are regulated by molecular networks comprised of different isoforms of the synthases adenylate cyclase or guanylate cyclase and the phosphodiesterases which degrade these compounds. In this paper, we employ a systems biology approach to develop mathematical models of these networks that, for the first time, take into account the different biochemical properties of the isoforms involved. To investigate the mechanisms underlying the joint regulation of cAMP and cGMP, we apply our models to analyse the regulation of cilia beat frequency in Paramecium by Ca(2+). Based on our analysis of these models, we propose that the diversity of isoform combinations that occurs in living cells provides an explanation for the huge variety of intracellular processes that are dependent on these networks. The inclusion of both G-protein receptor and Ca(2+)-dependent regulation of AC in our models allows us to propose a new explanation for the switching properties of G-protein subunits involved in nucleotide regulation. Analysis of the models suggests that, depending on whether the G-protein subunit is bound to AC, Ca(2+) can either activate or inhibit AC in a concentration-dependent manner. The resulting analysis provides an explanation for previous experimental results that showed that alterations in Ca(2+) concentrations can either increase or decrease cilia beat frequency over particular Ca(2+) concentration ranges

The scintillation and ionization yield of liquid xenon for nuclear recoils

XENON10 is an experiment designed to directly detect particle dark matter. It is a dual phase (liquid/gas) xenon time-projection chamber with 3D position imaging. Particle interactions generate a primary scintillation signal (S1) and ionization signal (S2), which are both functions of the deposited recoil energy and the incident particle type. We present a new precision measurement of the relative scintillation yield \leff and the absolute ionization yield Q_y, for nuclear recoils in xenon. A dark matter particle is expected to deposit energy by scattering from a xenon nucleus. Knowledge of \leff is therefore crucial for establishing the energy threshold of the experiment; this in turn determines the sensitivity to particle dark matter. Our \leff measurement is in agreement with recent theoretical predictions above 15 keV nuclear recoil energy, and the energy threshold of the measurement is 4 keV. A knowledge of the ionization yield \Qy is necessary to establish the trigger threshold of the experiment. The ionization yield \Qy is measured in two ways, both in agreement with previous measurements and with a factor of 10 lower energy threshold.Comment: 8 pages, 9 figures. To be published in Nucl. Instrum. Methods

Tawney and the third way

From the 1920s to the 1950s R. H. Tawney was the most influential socialist thinker in Britain. He articulated an ethical socialism at odds with powerful statist and mechanistic traditions in British socialist thinking. Tawney's work is thus an important antecedent to third way thinking. Tawney's religiously-based critique of the morality of capitalism was combined with a concern for detailed institutional reform, challenging simple dichotomies between public and private ownership. He began a debate about democratizing the enterprise and corporate governance though his efforts fell on stony ground. Conversely, Tawney's moralism informed a whole-hearted condemnation of market forces in tension with both his concern with institutional reform and modern third way thought. Unfortunately, he refused to engage seriously with emergent welfare economics which for many social democrats promised a more nuanced understanding of the limits of market forces. Tawney's legacy is a complex one, whose various elements form a vital part of the intellectual background to current third way thinking

3D Position Sensitive XeTPC for Dark Matter Search

The technique to realize 3D position sensitivity in a two-phase xenon time projection chamber (XeTPC) for dark matter search is described. Results from a prototype detector (XENON3) are presented.Comment: Presented at the 7th UCLA Symposium on "Sources and Detection of Dark Matter and Dark Energy in the Universe

Comment on "Evidence for Neutrinoless Double Beta Decay"

We comment on the recent claim for the experimental observation of neutrinoless double-beta decay. We discuss several limitations in the analysis provided in that paper and conclude that there is no basis for the presented claim.Comment: A comment written to Modern Physics Letters A. 4 pages, no figures. Updated version, accepted for publicatio

Status of the LUX Dark Matter Search

The Large Underground Xenon (LUX) dark matter search experiment is currently being deployed at the Homestake Laboratory in South Dakota. We will highlight the main elements of design which make the experiment a very strong competitor in the field of direct detection, as well as an easily scalable concept. We will also present its potential reach for supersymmetric dark matter detection, within various timeframes ranging from 1 year to 5 years or more.Comment: 4 pages, in proceedings of the SUSY09 conferenc