Adjusting the frequency of mammography screening on the basis of genetic risk: Attitudes among women in the UK.

Purpose To explore public attitudes towards modifying frequency of mammography screening based on genetic risk. Methods Home-based interviews were carried out with a population-based sample of 942 women aged 18–74 years in the UK. Demographic characteristics and perceived breast cancer (BC) risk were examined as predictors of support for risk-stratified BC screening and of the acceptability of raised or lowered screening frequency based on genetic risk, using multivariate logistic regression. Results Over two-thirds of respondents (65.8%) supported the idea of varying screening frequency on the basis of genetic risk. The majority (85.4%) were willing to have more frequent breast screening if they were found to be at higher risk, but fewer (58.8%) were willing to have less frequent screening if at lower risk (t (956) = 15.6, p < 0.001). Ethnic minority status was associated with less acceptability of more frequent screening (OR = 0.40, 95% CI = 0.21–0.74), but there were no other significant demographic correlates. Higher perceived risk of BC was associated with greater acceptability of more frequent screening (OR = 1.71, 95%CI = 1.27–2.30). Conclusion Women were positive about adjusting the frequency of mammography screening in line with personal genetic risk, but it will be important to develop effective communication materials to minimise resistance to reducing screening frequency for those at lower genetic risk

Fluctuations of fitness distributions and the rate of Muller's ratchet

The accumulation of deleterious mutations is driven by rare fluctuations which lead to the loss of all mutation free individuals, a process known as Muller's ratchet. Even though Muller's ratchet is a paradigmatic process in population genetics, a quantitative understanding of its rate is still lacking. The difficulty lies in the nontrivial nature of fluctuations in the fitness distribution which control the rate of extinction of the fittest genotype. We address this problem using the simple but classic model of mutation selection balance with deleterious mutations all having the same effect on fitness. We show analytically how fluctuations among the fittest individuals propagate to individuals of lower fitness and have a dramatically amplified effects on the bulk of the population at a later time. If a reduction in the size of the fittest class reduces the mean fitness only after a delay, selection opposing this reduction is also delayed. This delayed restoring force speeds up Muller's ratchet. We show how the delayed response can be accounted for using a path integral formulation of the stochastic dynamics and provide an expression for the rate of the ratchet that is accurate across a broad range of parameters.Comment: Genetics 201

Vr 2: a new apple scab resistance gene

Reports from several European countries of the breakdown of the Vf resistance, the most frequently used source of resistance in breeding programs against apple scab, emphasize the urgency of diversifying the basis of apple scab resistance and pyramiding different apple scab resistances with the use of their associated molecular markers. GMAL 2473 is an apple scab resistant selection thought to carry the resistance gene Vr. We report the identification by BSA of three AFLP markers and one RAPD marker associated with the GMAL 2473 resistance gene. SSRs associated with the resistance gene were found by (1) identifying the linkage group carrying the apple scab resistance and (2) testing the SSRs previously mapped in the same region. One such SSR, CH02c02a, mapped on linkage group 2, co-segregates with the resistance gene. GMAL 2473 was tested with molecular markers associated with other apple scab resistance genes, and accessions carrying known apple scab resistance genes were tested with the SSR linked to the resistance gene found in GMAL 2473. The results indicate that GMAL 2473 does not carry Vr, and that a new apple scab resistance gene, named Vr 2, has been identifie

Controlling circular polarization of light emitted by quantum dots using chiral photonic crystal slab

We study the polarization properties of light emitted by quantum dots that are embedded in chiral photonic crystal structures made of achiral planar GaAs waveguides. A modification of the electromagnetic mode structure due to the chiral grating fabricated by partial etching of the wave\-guide layer has been shown to result in a high circular polarization degree $\rho_c$ of the quantum dot emission in the absence of external magnetic field. The physical nature of the phenomenon can be understood in terms of the reciprocity principle taking into account the structural symmetry. At the resonance wavelength, the magnitude of $|\rho_c|$ is predicted to exceed 98%. The experimentally achieved value of $|\rho_c|=81$% is smaller, which is due to the contribution of unpolarized light scattered by grating defects, thus breaking its periodicity. The achieved polarization degree estimated removing the unpolarized nonresonant background from the emission spectra can be estimated to be as high as 96%, close to the theoretical prediction

Molecular markers linked to the apple scab resistance gene Vbj derived from Malus baccata jackii

Breeding for scab-resistant apple cultivars by pyramiding several resistance genes in the same genetic background is a promising way to control apple scab caused by the fungus Venturia inaequalis. To achieve this goal, DNA markers linked to the genes of interest are required in order to select seedlings with the desired resistance allele combinations. For several apple scab resistance genes, molecular markers are already available; but until now, none existed for the apple scab resistance gene Vbj originating from the crab apple Malus baccata jackii. Using bulk segregant analysis, three RAPD markers linked to Vbj were first identified. These markers were transformed into more reliable sequence-characterised amplified region (SCAR) markers that proved to be co-dominant. In addition, three SSR markers and one SCAR were identified by comparing homologous linkage groups of existing genetic maps. Discarding plants showing genotype-phenotype incongruence (GPI plants) plants, a linkage map was calculated. Vbj mapped between the markers CH05e03 (SSR) and T6-SCAR, at 0.6cM from CH05e03 and at 3.9cM from T6-SCAR. Without the removal of the GPI plants, Vbj was placed 15cM away from the closest markers. Problems and pitfalls due to GPI plants and the consequences for mapping the resistance gene accurately are discussed. Finally, the usefulness of co-dominant markers for pedigree analysis is also demonstrate

Detection of the fire blight biocontrol agent Bacillus subtilis BD170 (Biopro®) in a Swiss apple orchard

Fire blight, caused by Erwinia amylovora, is a major disease threat to apple, pear and other pome fruit worldwide. The disease is widespread in Europe and has recently become established in Switzerland. Antibiotics are the most effective controls used in North America but these are not permitted for agricultural use in most European countries. A newly registered biological control product Biopro®, based on the antagonist Bacillus subtilis strain BD170, is being used as an alternative strategy for fire blight management. A specific molecular marker was developed for monitoring the spread of this agent on blossoms after Biopro® spray application in a Swiss apple orchard throughout the bloom period for 2years. Direct spraying resulted in efficient primary colonisation of pistils in flowers that were open at the time of treatment. Subsequent bacterial dissemination (secondary colonisation) of flowers that were closed or at bud stage at the time of treatment was observed but was found to be dependent on the timing of treatments relative to bloom stage in the orchard. Foraging honeybees were shown to be disseminators of Biopro®. We also report detection of the biocontrol agent in honey collected from hives where bees were exposed by placing Biopro® at the entrance or in the hatching nest and from hives that were simply placed in sprayed orchard

Inviting end-of-life talk in initial CALM therapy sessions: A conversation analytic study

OBJECTIVE: To examine how end-of-life talk is initiated in CALM therapy sessions with advanced cancer patients. METHODS: Conversation analysis was used to systematically examine the sequences where talk about death was raised in the first sessions of ten patients. RESULTS: Open questions about the patients' experiences, feelings or understanding in the context of talk about their troubles, were found to regularly elicit talk concerning end-of-life. These questions were designed in ways that invite patients to discuss troubling aspects of their cancer journey, without making discussion of this topic an interactional requirement. That is, the interactional work required to not engage in such talk is minimised. This choice is provided through the open question design, the degree to which negative feeling descriptors are specified, and the sequential context of the question. CONCLUSION: The analysis shows that therapists provide patients with the opportunity to talk about end-of-life in a way that is supportive of the therapeutic relationship. The readiness of patients to engage in end-of-life talk displays the salience of this topic, as well as the reflective space provided by CALM therapy. PRACTICE IMPLICATIONS: The results provide important insight into the process of CALM therapy, which can be used to guide training

Portable Catapult Launcher For Small Aircraft

An apparatus for launching an aircraft having a multiplicity of interconnected elongated tracks of rigid material forming a track system and wherein each elongated track has a predetermined elongated track cross-sectional design, a winch system connected to the track system wherein the winch system has a variable mechanical advantage, one or more elongated elastic members wherein one end of each of the one or more elongated elastic members is adjustably connected to the track system, and a carrier slidably mounted to the track system wherein the canier is connected to the winch system and to the other end of each of the one or more elongated elastic members

Population-based, risk-stratified genetic testing for ovarian cancer risk: a focus group study

Study Purpose: A population-based risk stratification programme for ovarian cancer (OC) may improve OC survival by identifying women at increased risk and implementing an appropriate risk management strategy. The present study explored attitudes towards an OC risk stratification programme incorporating predictive genetic testing and risk-stratified screening as part of a larger study investigating OC screening. Methods: Focus groups consisting of 56 members of the general public (mean age 45 years; 34% non-white) were conducted using a hypothetical scenario. The group sessions were recorded, transcribed verbatim and analysed using Framework Analysis. Results: There was strong support for the proposed programme. Genetic testing and risk-stratified screening was thought to raise awareness, offer reassurance and offer opportunities for early intervention. Anxiety was only mentioned in relation to receiving a diagnosis of OC and not with screening per se. Perhaps because lay models of cancer already embrace both environmental and genetic factors, a low-risk result was not anticipated to result in a false sense of immunity. Unexpectedly, participants also wanted to receive cancer prevention advice in conjunction with genetic testing; screening alone was not regarded as sufficient. Conclusion: The encouraging results from this small study warrant further large-scale research into risk-stratified OC screening

Neurospora crassa Light Signal Transduction Is Affected by ROS

In the ascomycete fungus Neurospora crassa blue-violet light controls the expression of genes responsible for differentiation of reproductive structures, synthesis of secondary metabolites, and the circadian oscillator activity. A major photoreceptor in Neurospora cells is WCC, a heterodimeric complex formed by the PAS-domain-containing polypeptides WC-1 and WC-2, the products of genes white collar-1 and white collar-2. The photosignal transduction is started by photochemical activity of an excited FAD molecule noncovalently bound by the LOV domain (a specialized variant of the PAS domain). The presence of zinc fingers (the GATA-recognizing sequences) in both WC-1 and WC-2 proteins suggests that they might function as transcription factors. However, a critical analysis of the phototransduction mechanism considers the existence of residual light responses upon absence of WCC or its homologs in fungi. The data presented point at endogenous ROS generated by a photon stimulus as an alternative input to pass on light signals to downstream targets