Cost-effectiveness of the Manchester approach to identifying Lynch syndrome in women with endometrial cancer

This is the final version. Available on open access from MDPI via the DOI in this recordLynch syndrome (LS) is a hereditary cancer syndrome responsible for 3% of all endometrial cancer and 5% in those aged under 70 years. It is unclear whether universal testing for LS in endometrial cancer patients would be cost-effective. The Manchester approach to identifying LS in endometrial cancer patients uses immunohistochemistry (IHC) to detect mismatch repair (MMR) deficiency, incorporates testing for MLH1 promoter hypermethylation, and genetic testing for pathogenic MMR variants. We aimed to assess the cost-effectiveness of the Manchester approach based on primary research data from clinical practice in Manchester. The PETALS study informed estimates of diagnostic performances for a number of different strategies. A recent microcosting study was adapted and used to estimate diagnostic costs. A Markov model was used to predict long-term costs and health outcomes (measured in quality-adjusted life years, QALYs) for individuals and their relatives. Bootstrapping and probabilistic sensitivity analysis were used to estimate the uncertainty in cost-effectiveness. The Manchester approach dominated other reflex testing strategies when considering diagnostic costs and Lynch syndrome cases identified. When considering long-term costs and QALYs the Manchester approach was the optimal strategy, costing £5459 per QALY gained (compared to thresholds of £20,000 to £30,000 per QALY commonly used in the NHS). Cost-effectiveness is not an argument for restricting testing to younger patients or those with a strong family history. Universal testing for Lynch syndrome in endometrial cancer patients is expected to be cost-effective in the UK NHS, and the Manchester approach is expected to be the optimal testing strategy.Medical Research Council (MRC)National Institute for Health Research (NIHR

Tincurrin : a new biscuit wheat

Although a demand has existed both locally and overseas for soft wheat suitable for biscuits, cakes and various confectioneries, production has been very limited. In 1978 farmers in the soft wheat area will be able to grow the higher yielding variety Tincurrin. It is recommended for general sowing to replace all varieties grown at present in the soft wheat areas as defined.Exceptions may prevail in areas prone to rust snd septoria problems

Response Inhibition and ADHD Traits: Correlates and Heritability in a Community Sample

Endophenotypes or intermediate phenotypes are of great interest in neuropsychiatric genetics because of their potential for facilitating gene discovery. We evaluated response inhibition, latency and variability measures derived from the stop task as endophenotypes of ADHD by testing whether they were related to ADHD traits in the general population, heritable and shared genetic risk with ADHD traits. Participants were 16,099 children and adolescents, ages 6 to 18æyears who visited a local science center. We measured ADHD traits using the Strengths and Weaknesses of ADHD-symptoms and Normal-Behavior (SWAN) rating scale and performance on the stop signal task (SST)?response inhibition (SSRT), response latency (GoRT), and response variability (GoRTSD). Regression analysis was used to assess the relationship of cognitive measures and ADHD traits while controlling for family, age, sex, ethnicity, socioeconomic status and treatment status. Heritability of ADHD and cognitive traits was estimated using SOLAR in 7,483 siblings from 3,507 families that included multiple siblings. Bivariate relationships between pairs of variables were examined. Individuals with greater ADHD trait scores had worse response inhibition, slower response latency, and greater variability. Younger participants and girls had inferior performance although the gender effects were minimal and evident in youngest participants. Inhibition, latency, variability, total ADHD traits, inattention and hyperactivity-impulsivity scores were significantly heritable. ADHD traits and inhibition, but not latency or variability were coheritable. In the largest study in the general population, we found support for the validity of response inhibition as an endophenotype of ADHD. Electronic supplementary material The online version of this article (doi:10.1007/s10802-012-9693-9) contains supplementary material, which is available to authorized users

The prevalence of mismatch repair deficiency in ovarian cancer: A systematic review and meta-analysis

This is the final version. Available on open access from Wiley via the DOI in this recordData availability statement: All data contained here within this article is available on request from the corresponding authorOvarian cancer (OC) is the least survivable gynecological malignancy and presents late. Five-year survival for OC is around 45% increasing the need for innovative treatments. Checkpoint inhibitors have shown significant clinical efficacy in mismatch repair deficient (MMRd) cancers and could be a powerful treatment in OC. However, their application in OC is limited due to the lack of data on the prevalence of MMRd. The aim of our study was to conduct a systematic review of the literature and meta-analysis to provide an accurate estimate of the prevalence of MMRd in OC. We followed PRISMA guidelines throughout. Studies were identified by electronic searches of Medline, Embase, Cochrane CENTRAL and Web of Science followed by citation searching. Studies not written in English were excluded. All studies were reviewed by at least two independent reviewers. Proportions of test positivity were calculated by random and fixed-effects meta-analysis models. I2 score was used to assess heterogeneity across studies. In total 54 studies were included with 17 532 analyzed for MMRd. The overall proportions of MMRd by immunohistochemistry and microsatellite instability analysis were 6.7% and 10.4%, respectively. MMRd was reported in all histotypes of epithelial OC but was most common in endometrioid OC. We estimate that on average 46.7% (95% CI: 28.8-65.4) of ovarian carcinomas showing MMRd by IHC had a germline path_MMR variant identified. OC in those with Lynch syndrome seems to present at an earlier age and stage. Studies however were generally of low quality and there was a high degree of heterogeneity. A significant minority (up to 16%) of OC displays MMRd and, therefore, could be amenable to checkpoint inhibition therapy. However, the current literature base is of limited quality and therefore high-quality prospective studies exploring MMRd in OC with the use of multimodal testing are required. In addition, trials researching efficacy of checkpoint inhibition in MMRd OC are needed

Applying a brain-computer interface to support motor imagery practice in people with stroke for upper limb recovery: A feasibility study

<p>Abstract</p> <p>Background</p> <p>There is now sufficient evidence that using a rehabilitation protocol involving motor imagery (MI) practice in conjunction with physical practice (PP) of goal-directed rehabilitation tasks leads to enhanced functional recovery of paralyzed limbs among stroke sufferers. It is however difficult to confirm patient engagement during an MI in the absence of any on-line measure. Fortunately an EEG-based brain-computer interface (BCI) can provide an on-line measure of MI activity as a neurofeedback for the BCI user to help him/her focus better on the MI task. However initial performance of novice BCI users may be quite moderate and may cause frustration. This paper reports a pilot study in which a BCI system is used to provide a computer game-based neurofeedback to stroke participants during the MI part of a protocol.</p> <p>Methods</p> <p>The participants included five chronic hemiplegic stroke sufferers. Participants received up to twelve 30-minute MI practice sessions (in conjunction with PP sessions of the same duration) on 2 days a week for 6 weeks. The BCI neurofeedback performance was evaluated based on the MI task classification accuracy (CA) rate. A set of outcome measures including action research arm test (ARAT) and grip strength (GS), was made use of in assessing the upper limb functional recovery. In addition, since stroke sufferers often experience physical tiredness, which may influence the protocol effectiveness, their fatigue and mood levels were assessed regularly.</p> <p>Results</p> <p>Positive improvement in at least one of the outcome measures was observed in all the participants, while improvements approached a minimal clinically important difference (MCID) for the ARAT. The on-line CA of MI induced sensorimotor rhythm (SMR) modulation patterns in the form of lateralized event-related desynchronization (ERD) and event-related synchronization (ERS) effects, for novice participants was in a moderate range of 60-75% within the limited 12 training sessions. The ERD/ERS change from the first to the last session was statistically significant for only two participants.</p> <p>Conclusions</p> <p>Overall the crucial observation is that the moderate BCI classification performance did not impede the positive rehabilitation trends as quantified with the rehabilitation outcome measures adopted in this study. Therefore it can be concluded that the BCI supported MI is a feasible intervention as part of a post-stroke rehabilitation protocol combining both PP and MI practice of rehabilitation tasks. Although these findings are promising, the scope of the final conclusions is limited by the small sample size and the lack of a control group.</p

Energy Dependence of Nuclear Transparency in C(p,2p) Scattering

The transparency of carbon for (p,2p) quasi-elastic events was measured at beam energies ranging from 6 to 14.5 GeV at 90 degrees c.m. The four momentum transfer squared q*q ranged from 4.8 to 16.9 (GeV/c)**2. We present the observed energy dependence of the ratio of the carbon to hydrogen cross sections. We also apply a model for the nuclear momentum distribution of carbon to normalize this transparency ratio. We find a sharp rise in transparency as the beam energy is increased to 9 GeV and a reduction to approximately the Glauber level at higher energies.Comment: 4 pages, 2figures, submitted to PR