Non-uptake of predictive genetic testing for BRCA1/2 among relatives of known carriers: Attributes, cancer worry, and barriers to testing in a multicenter clinical cohort

BRCA1/2 test decliners/deferrers have received almost no attention in the literature and this is the first study of this population in the United Kingdom. The aim of this multicenter study is to examine the attributes of a group of individuals offered predictive genetic testing for breast/ovarian cancer predisposition who did not wish to proceed with testing at the time of entry into this study. This forms part of a larger study involving 9 U.K. centers investigating the psychosocial impact of predictive genetic testing for BRCA1/2. Cancer worry and reasons for declining or deferring BRCA1/2 predictive genetic testing were evaluated by questionnaire following genetic counseling. A total of 34 individuals declined the offer of predictive genetic testing. Compared to the national cohort of test acceptors, test decliners are significantly younger. Female test decliners have lower levels of cancer worry than female test acceptors. Barriers to testing include apprehension about the result, traveling to the genetics clinic, and taking time away from work/family. Women are more likely than men to worry about receiving less screening if found not to be a carrier. The findings do not indicate that healthy BRCA1/2 test decliners are a more vulnerable group in terms of cancer worry. However, barriers to testing need to be discussed in genetic counseling.

A Cluster Randomized Controlled Trial of an Adapted U.S. Model of Pharmaceutical Care for Nursing Home Residents in Northern Ireland (Fleetwood Northern Ireland Study): A Cost-Effectiveness Analysis

OBJECTIVES: To evaluate the cost-effectiveness of an adapted U.S. model of pharmaceutical care to improve psychoactive prescribing for nursing home residents in Northern Ireland (Fleetwood NI Study).
DESIGN: Economic evaluation alongside a cluster randomized controlled trial.
SETTING: Nursing homes in NI randomized to intervention (receipt of the adapted model of care; n511) or control (usual care continued; n511).
PARTICIPANTS: Residents aged 65 and older who provided informed consent (N5253; 128 intervention, 125 control) and who had full resource use data at 12 months.
INTERVENTION: Trained pharmacists reviewed intervention home residents’ clinical and prescribing information for 12 months, applied an algorithm that guided them in assessing the appropriateness of psychoactive medication, and worked with prescribers (general practitioners) to make changes. The control homes received usual care in which there was no pharmacist intervention.
MEASUREMENTS: The proportion of residents prescribed one or more inappropriate psychoactive medications (according to standardized protocols), costs, and a cost-effectiveness acceptability curve. The latter two outcomes are the focus for this article.
RESULTS: The proportions of residents receiving inappropriate psychoactive medication at 12 months in the intervention and control group were 19.5% and 50.4%, respectively. The mean cost of healthcare resources used per resident per year was $4,923 (95% con?dence interval.

Regarding “Co-expression of SNAIL and TWIST determines prognosis in estrogen receptor-positive early breast cancer patients”

We read the interesting research article published by van Nes et al. [1], which described the use of Snail and TWIST together in the prognosis of breast cancer, and in particular in estrogen receptor (ER)-positive breast cancer patients.

Donepezil and memantine for moderate-to-severe Alzheimer's disease

Background: Clinical trials have shown the benefits of cholinesterase inhibitors for the treatment of mild-to-moderate Alzheimer's disease. It is not known whether treatment benefits continue after the progression to moderate-to-severe disease. Methods: We assigned 295 community-dwelling patients who had been treated with donepezil for at least 3 months and who had moderate or severe Alzheimer's disease (a score of 5 to 13 on the Standardized Mini-Mental State Examination [SMMSE, on which scores range from 0 to 30, with higher scores indicating better cognitive function]) to continue donepezil, discontinue donepezil, discontinue donepezil and start memantine, or continue donepezil and start memantine. Patients received the study treatment for 52 weeks. The coprimary outcomes were scores on the SMMSE and on the Bristol Activities of Daily Living Scale (BADLS, on which scores range from 0 to 60, with higher scores indicating greater impairment). The minimum clinically important differences were 1.4 points on the SMMSE and 3.5 points on the BADLS.
Results: Patients assigned to continue donepezil, as compared with those assigned to discontinue donepezil, had a score on the SMMSE that was higher by an average of 1.9 points (95% confidence interval [CI], 1.3 to 2.5) and a score on the BADLS that was lower (indicating less impairment) by 3.0 points (95% CI, 1.8 to 4.3) (P<0.001 for both comparisons). Patients assigned to receive memantine, as compared with those assigned to receive memantine placebo, had a score on the SMMSE that was an average of 1.2 points higher (95% CI, 0.6 to 1.8; P<0.001) and a score on the BADLS that was 1.5 points lower (95% CI, 0.3 to 2.8; P = 0.02). The efficacy of donepezil and of memantine did not differ significantly in the presence or absence of the other. There were no significant benefits of the combination of donepezil and memantine over donepezil alone.
Conclusions: In patients with moderate or severe Alzheimer's disease, continued treatment with donepezil was associated with cognitive benefits that exceeded the minimum clinically important difference and with significant functional benefits over the course of 12 months. (Funded by the U.K. Medical Research Council and the U.K. Alzheimer's Society; Current Controlled Trials number, ISRCTN49545035).

Determining the minimum clinically important differences for outcomes in the DOMINO trial

Although less likely to be reported in clinical trials than expressions of the statistical significance of differences in outcomes, whether or not a treatment has delivered a specified minimum clinically important difference (MCID) is also relevant to patients and their caregivers and doctors. Many dementia treatment randomised controlled trials (RCTs) have not reported MCIDs and, where they have been done, observed differences have not reached these.

DOMINO-AD protocol:donepezil and memantine in moderate to severe Alzheimer's disease - a multicentre RCT

Alzheimer's disease (AD) is the commonest cause of dementia. Cholinesterase inhibitors, such as donepezil, are the drug class with the best evidence of efficacy, licensed for mild to moderate AD, while the glutamate antagonist memantine has been widely prescribed, often in the later stages of AD. Memantine is licensed for moderate to severe dementia in AD but is not recommended by the England and Wales National Institute for Health and Clinical Excellence. However, there is little evidence to guide clinicians as to what to prescribe as AD advances; in particular, what to do as the condition progresses from moderate to severe. Options include continuing cholinesterase inhibitors irrespective of decline, adding memantine to cholinesterase inhibitors, or prescribing memantine instead of cholinesterase inhibitors. The aim of this trial is to establish the most effective drug option for people with AD who are progressing from moderate to severe dementia despite treatment with donepezil.

Sub-luminous type Ia supernovae from the mergers of equal-mass white dwarfs with mass 0.9M

Type Ia supernovae are thought to result from thermonuclear explosions of carbong'oxygen white dwarf stars. Existing models generally explain the observed properties, with the exception of the sub-luminous 1991bg-like supernovae. It has long been suspected that the merger of two white dwarfs could give rise to a type Ia event, but hitherto simulations have failed to produce an explosion. Here we report a simulation of the merger of two equal-mass white dwarfs that leads to a sub-luminous explosion, although at the expense of requiring a single common-envelope phase, and component masses of 0.9M. The light curve is too broad, but the synthesized spectra, red colour and low expansion velocities are all close to what is observed for sub-luminous 1991bg-like events. Although the mass ratios can be slightly less than one and still produce a sub-luminous event, the masses have to be in the range 0.83M to 0.9M. © 2010 Macmillan Publishers Limited. All rights reserved.

Corporate Governance in Canadian and US Credit Unions

This report, a collaborative effort between the Filene Research Institute and the Credit Union Central of Canada, with participation from the Desjardins Group, follows on two recent governance projects: Tracking the Relationship Between Credit Union Governance and Performance and a three-part series by Professor Robert Hoel about how boards can add more value. Beyond these, the academic literature of corporate governance is well developed, so this study includes an in-depth review of financial institution governance research and calls out the differences between credit unions and other firms. Also, because surveys can only go so far in teasing out insights, the authors followed up with a dozen interviews with credit unions of all sizes across all three major North American credit union systems.

Because the report is survey-based, large swaths of the findings compare major and minor details of different (and often not-so-different) approaches to governance in the three systems and among differently sized credit unions. From those comparisons, some interesting differences emerge. For example, as a federated system, Desjardins excels at some aspects of board development and system governance in ways that the more atomized US and Canadian credit union systems do not.

Improving the Fuel Economy of a Tuned 600cc FSAE Engine

To maintain its relevance, motorsport cannot be exempt from
the trend of increasing fuel economy. This bears obvious
competitive benefits as well, either in decreasing the
frequency of pit stops or the mass of fuel carried. Given the
increased points weighting of fuel economy for the Formula
Student (FS) competition, a complete analysis was performed
on the Queen's Formula Racing 600cc motorcycle engine in
preparation for the 2011 competition.
The criteria for such high performance fuel economy differ to
a degree from most mass transportation counterparts and were
divided into three distinct regimes; full load, part load and no
load conditions.
Full load positions naturally demand maximum torque for
performance but that does not imply that fuel savings cannot
be made whilst preserving this. The point at which maximum
torque is produced with minimum air -fuel ratio, Leanest
mixture for Best Torque (LBT), was therefore sought and
mapped for full load.
At part load, torque is less of a concern, and maintaining a
sustainable engine temperature and transient response become
more important. With decreasing AFR, engine temperatures
can rise dramatically so temperatures were measured close to
the exhaust port for a wide range of air-fuel ratios.
Competition track data was analysed to highlight key part load
operating regions and these were mapped according to
measured safe temperature limits. Torque response to a step
throttle change was also measured to ensure suitable engine
transient performance was maintained.
At no load conditions, with low engine speed only idle
conditions need to be satisfied. In the situation where the
engine is still at high speed without load, the engine is being
motored and no fuel is required. An overrun fuel cut was
employed to reflect this giving significant fuel savings. The
effect on torque and engine pickup was measured.
Modifications were also made to the fuel injector location to
improve fuel mixing and evaporation at this lower air flow
condition.
These mapping regimes were implemented and tested using
fully transient lap simulations using competition track data
and a four quadrant AC engine dynamometer. The experiment
indicated a reduction in fuel consumption for 22 laps of the FS
track from 5.08litres to 3.67litres, around 27% in total. The
actual fuel used at the 2011 competition was 3.6 litres while
placing 8th in the endurance event, further validating the
benefits of these mapping regimes.

Marie Sallé, a Wise Professional Woman of Influence

This study maps the extent of Sallé's influence while identifying her self agency in moulding her image and developing her career.

WO 2014087023 An Amphipathic Peptide

http://www.google.com/patents/EP2928909A1?cl=en