Assessing women's preferences towards tests that may reveal uncertain results from prenatal genomic testing: Development of attributes for a discrete choice experiment, using a mixed-methods design

Prenatal DNA tests, such as chromosomal microarray analysis or exome sequencing, increase the likelihood of receiving a diagnosis when fetal structural anomalies are identified. However, some parents will receive uncertain results such as variants of uncertain significance and secondary findings. We aimed to develop a set of attributes and associated levels for a discrete-choice experiment (DCE) that will examine parents' preferences for tests that may reveal uncertain test results. A two phase mixed-methods approach was used to develop attributes for the DCE. In Phase 1, a “long list” of candidate attributes were identified via two approaches: 1) a systematic review of the literature around parental experiences of uncertainty following prenatal testing; 2) 16 semi-structured interviews with parents who had experienced uncertainty during pregnancy and 25 health professionals who return uncertain prenatal results. In Phase 2, a quantitative scoring exercise with parents prioritised the candidate attributes. Clinically appropriate levels for each attribute were then developed. A final set of five attributes and levels were identified: likelihood of getting a result, reporting of variants of uncertain significance, reporting of secondary findings, time taken to receive results, and who tells you about your result. These attributes will be used in an international DCE study to investigate preferences and differences across countries. This research will inform best practice for professionals supporting parents to manage uncertainty in the prenatal setting

Dealing with uncertain results from chromosomal microarray and exome sequencing in the prenatal setting: an international cross-sectional study with healthcare professionals.

OBJECTIVES: To conduct qualitative interviews with healthcare providers working in different countries to understand their experiences of dealing with uncertain results from prenatal chromosome microarray analysis (CMA) and exome sequencing (ES). METHODS: Semi-structured interviews with 31 healthcare providers who report or return prenatal CMA and/or ES results (clinicians, genetic counsellors and clinical scientists) in six countries with differing healthcare systems; Australia (4), Denmark (5), Netherlands (6), Singapore (4), Sweden (6) and United Kingdom (6). The topic guide explored the main sources of uncertainty and their management. RESULTS: There was variation in reporting practices both between and across countries for variants of uncertain significance (VUS), however, there was broad agreement on reporting practices for incidental findings. There was also variation in who decides what results are reported (clinical scientists or clinicians). Technical limitations and lack of knowledge (to classify variants and of prenatal phenotypes) were significant challenges, as were turnaround times and lack of guidelines. CONCLUSION: Health professionals around the globe are dealing with similar sources of uncertainty, but managing them in different ways, Continued dialogue with international colleagues on ways of managing uncertain results is important to compare and contrast the benefits and limitations of the different approaches. This article is protected by copyright. All rights reserved

Smokers' recall of Australian graphic cigarette packet warnings & awareness of associated health effects, 2005-2008

Extent: 11p.Background: In 2006, Australia introduced graphic cigarette packet warnings. The new warnings include one of 14 pictures, many depicting tobacco-related pathology. The warnings were introduced in two sets; Set A in March and Set B from November. This study explores their impact on smokers’ beliefs about smoking related illnesses. This study also examines the varying impact of different warnings, to see whether warnings with visceral images have greater impact on smokers’ beliefs than other images. Methods: Representative samples of South Australian smokers were interviewed in four independent cross-sectional omnibus surveys; in 2005 (n = 504), 2006 (n = 525), 2007 (n = 414) and 2008 (n = 464). Results: Unprompted recall of new graphic cigarette warnings was high in the months following their introduction, demonstrating that smokers’ had been exposed to them. Smokers also demonstrated an increase in awareness about smoking-related diseases specific to the warning messages. Warnings that conveyed new information and had emotive images demonstrated greater impact on recall and smokers’ beliefs than more familiar information and less emotive images. Conclusions: Overall graphic pack warnings have had the intended impact on smokers. Some have greater impact than others. The implications for policy makers in countries introducing similar warnings are that fresh messaging and visceral images have the greatest impact.Caroline L Miller, Pascale G Quester, David J Hill and Janet E Hille

Immunostimulation and Immunoinhibition of Premalignant Lesions

BACKGROUND: The immune reaction may be either stimulatory or inhibitory to tumor growth, depending upon the local ratio of immune reactants to tumor cells. HYPOTHESIS: A tumor-stimulatory immune response may be essential for survival of a neoplasm in vivo and for the biological progression from a premalignant lesion to a malignancy. Neither a positive nor a negative correlation between the magnitude of an immune-cell infiltrate and a cancer's prognosis can reveal whether the infiltrate was stimulating or inhibiting to the tumor's growth unless the position on the nonlinear curve that relates tumor growth to the magnitude of the immune reaction is known. DISCUSSION: This hypothesis is discussed in relation to the development of human malignant melanomas and colorectal cancers

Rabies screen reveals GPe control of cocaine-triggered plasticity.

Identification of neural circuit changes that contribute to behavioural plasticity has routinely been conducted on candidate circuits that were preselected on the basis of previous results. Here we present an unbiased method for identifying experience-triggered circuit-level changes in neuronal ensembles in mice. Using rabies virus monosynaptic tracing, we mapped cocaine-induced global changes in inputs onto neurons in the ventral tegmental area. Cocaine increased rabies-labelled inputs from the globus pallidus externus (GPe), a basal ganglia nucleus not previously known to participate in behavioural plasticity triggered by drugs of abuse. We demonstrated that cocaine increased GPe neuron activity, which accounted for the increase in GPe labelling. Inhibition of GPe activity revealed that it contributes to two forms of cocaine-triggered behavioural plasticity, at least in part by disinhibiting dopamine neurons in the ventral tegmental area. These results suggest that rabies-based unbiased screening of changes in input populations can identify previously unappreciated circuit elements that critically support behavioural adaptations

A Step Towards Seascape Scale Conservation: Using Vessel Monitoring Systems (VMS) to Map Fishing Activity

Published onlineJournal ArticleResearch Support, Non-U.S. Gov'tBACKGROUND: Conservation of marine ecosystems will require a holistic understanding of fisheries with concurrent spatial patterns of biodiversity. METHODOLOGY/PRINCIPAL FINDINGS: Using data from the UK Government Vessel Monitoring System (VMS) deployed on UK-registered large fishing vessels we investigate patterns of fisheries activity on annual and seasonal scales. Analysis of VMS data shows that regions of the UK European continental shelf (i.e. Western Channel and Celtic Sea, Northern North Sea and the Goban Spur) receive consistently greater fisheries pressure than the rest of the UK continental shelf fishing zone. CONCLUSIONS/SIGNIFICANCE: VMS provides a unique and independent method from which to derive patterns of spatially and temporally explicit fisheries activity. Such information may feed into ecosystem management plans seeking to achieve sustainable fisheries while minimising putative risk to non-target species (e.g. cetaceans, seabirds and elasmobranchs) and habitats of conservation concern. With multilateral collaboration VMS technologies may offer an important solution to quantifying and managing ecosystem disturbance, particularly on the high-seas.MJW is supported by a Natural Environment Research Council PhD studentship (NER/S/A/2004/12980) at the University of Exeter (Cornwall Campus). BJG receives funding from the European Social Fund

Lutein supplementation in retinitis pigmentosa: PC-based vision assessment in a randomized double-masked placebo-controlled clinical trial [NCT00029289]

BACKGROUND: There is no generally accepted medical or surgical treatment to stop the progressive course of retinitis pigmentosa. Previous studies have suggested lutein as a potential treatment with positive effects on macular pigment density. The objective of this study was to examine the effect of lutein supplementation on preservation of visual function in patients with retinitis pigmentosa (RP) METHODS: In a double-masked randomized placebo-controlled phase I/II clinical trial with a cross-over design, 34 adult patients with RP were randomized to two groups. One group, consisted of 16 participants, received lutein supplementation (10 mg/d for 12 wks followed by 30 mg/d) for the first 24 weeks and then placebo for the following 24 weeks, while the other group included 18 participants for whom placebo (24 weeks) was administered prior to lutein. Visual acuity, contrast sensitivity, and central visual field were measured at different illumination levels at baseline and every week using a PC-based test at home. RESULTS: For visual acuity (VA) at normal illumination level, treatment with lutein reduced logMAR, i.e. improved VA, but this effect was not statistically significant. The changes in normal (100%), low (4%), and very low (0.1%) illumination log CS were not statistically significant (p-values: 0.34, 0.23, and 0.32, respectively). Lutein had a statistically significant effect on visual field (p-value: 0.038) and this effect increased in the model assuming a 6-week delay in effect of lutein. Comparing the development of vision measures against the natural loss expected to occur over the course of 48 weeks, most measures showed reduced decline, and these reductions were significant for normal illumination VA and CS. CONCLUSION: These results suggest that lutein supplementation improves visual field and also might improve visual acuity slightly, although these results should be interpreted cautiously. As a combined phase I and II clinical trial, this study demonstrated the efficacy and safety of lutein supplementation

Associations with photoreceptor thickness measures in the UK Biobank.

Spectral-domain OCT (SD-OCT) provides high resolution images enabling identification of individual retinal layers. We included 32,923 participants aged 40-69 years old from UK Biobank. Questionnaires, physical examination, and eye examination including SD-OCT imaging were performed. SD OCT measured photoreceptor layer thickness includes photoreceptor layer thickness: inner nuclear layer-retinal pigment epithelium (INL-RPE) and the specific sublayers of the photoreceptor: inner nuclear layer-external limiting membrane (INL-ELM); external limiting membrane-inner segment outer segment (ELM-ISOS); and inner segment outer segment-retinal pigment epithelium (ISOS-RPE). In multivariate regression models, the total average INL-RPE was observed to be thinner in older aged, females, Black ethnicity, smokers, participants with higher systolic blood pressure, more negative refractive error, lower IOPcc and lower corneal hysteresis. The overall INL-ELM, ELM-ISOS and ISOS-RPE thickness was significantly associated with sex and race. Total average of INL-ELM thickness was additionally associated with age and refractive error, while ELM-ISOS was additionally associated with age, smoking status, SBP and refractive error; and ISOS-RPE was additionally associated with smoking status, IOPcc and corneal hysteresis. Hence, we found novel associations of ethnicity, smoking, systolic blood pressure, refraction, IOPcc and corneal hysteresis with photoreceptor thickness

Computer simulation of breast reduction surgery

Background: Plastic surgery of the breast, particularly breast reduction, is considered difficult. It can become a challenge for a less experienced surgeon to understand exactly what to do when facing a particular type of breast and how to avoid unsatisfactory results. Methods: The goal of this study was to create a computer model of the breast that provides a basis for the simulation of breast surgery, particularly breast reduction. The reconstruction of elastic parameters is based on observations of the breast with the patient in different positions. Results: It is shown that several measurements with the patient in different positions allow one to choose the parameters of the model and determine the elastic coefficients of the breast and the skin. The geometry of the breast before and after surgery is simulated. A qualitative study of the incision parameters’ influence on the final geometry of the breast is presented. Conclusion: The developed methodology and software allow one to estimate the form of the breast after the surgery by knowing its form before surgery and taking into consideration the parameters of incision applied by the surgeon at the time of surgery. The described approach can be used for the qualitative and quantitative study of breast reduction surgery with a satisfactory result. Level of Evidence: V (This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266.