Are estrogen receptor-positive breast cancers in BRCA1 mutation carriers sporadic?

There is a strong association between BRCA1 mutation carrier status and estrogen receptor-negative breast cancer. This has led to the idea that estrogen receptor-positive breast cancers in BRCA1 mutation carriers may be incidental or sporadic in nature and not as a direct result of BRCA1 dysfunction. A recent paper in Breast Cancer Research challenges this view

Eyetracking Metrics in Young Onset Alzheimer’s Disease: A Window into Cognitive Visual Functions

Young onset Alzheimer’s disease (YOAD) is defined as symptom onset before the age of 65 years and is particularly associated with phenotypic heterogeneity. Atypical presentations, such as the clinic-radiological visual syndrome posterior cortical atrophy (PCA), often lead to delays in accurate diagnosis. Eyetracking has been used to demonstrate basic oculomotor impairments in individuals with dementia. In the present study, we aim to explore the relationship between eyetracking metrics and standard tests of visual cognition in individuals with YOAD. Fifty-seven participants were included: 36 individuals with YOAD (n =  26 typical AD; n =  10 PCA) and 21 age-matched healthy controls. Participants completed three eyetracking experiments: fixation, pro-saccade, and smooth pursuit tasks. Summary metrics were used as outcome measures and their predictive value explored looking at correlations with visuoperceptual and visuospatial metrics. Significant correlations between eyetracking metrics and standard visual cognitive estimates are reported. A machine-learning approach using a classification method based on the smooth pursuit raw eyetracking data discriminates with approximately 95% accuracy patients and controls in cross-validation tests. Results suggest that the eyetracking paradigms of a relatively simple and specific nature provide measures not only reflecting basic oculomotor characteristics but also predicting higher order visuospatial and visuoperceptual impairments. Eyetracking measures can represent extremely useful markers during the diagnostic phase and may be exploited as potential outcome measures for clinical trials

Evolution of spiral and scroll waves of excitation in a mathematical model of ischaemic border zone

Abnormal electrical activity from the boundaries of ischemic cardiac tissue is recognized as one of the major causes in generation of ischemia-reperfusion arrhythmias. Here we present theoretical analysis of the waves of electrical activity that can rise on the boundary of cardiac cell network upon its recovery from ischaemia-like conditions. The main factors included in our analysis are macroscopic gradients of the cell-to-cell coupling and cell excitability and microscopic heterogeneity of individual cells. The interplay between these factors allows one to explain how spirals form, drift together with the moving boundary, get transiently pinned to local inhomogeneities, and finally penetrate into the bulk of the well-coupled tissue where they reach macroscopic scale. The asymptotic theory of the drift of spiral and scroll waves based on response functions provides explanation of the drifts involved in this mechanism, with the exception of effects due to the discreteness of cardiac tissue. In particular, this asymptotic theory allows an extrapolation of 2D events into 3D, which has shown that cells within the border zone can give rise to 3D analogues of spirals, the scroll waves. When and if such scroll waves escape into a better coupled tissue, they are likely to collapse due to the positive filament tension. However, our simulations have shown that such collapse of newly generated scrolls is not inevitable and that under certain conditions filament tension becomes negative, leading to scroll filaments to expand and multiply leading to a fibrillation-like state within small areas of cardiac tissue.Comment: 26 pages, 13 figures, appendix and 2 movies, as accepted to PLoS ONE 2011/08/0

The functional neuroanatomy of musical memory in Alzheimer's disease

BACKGROUND: Memory for music has attracted much recent interest in Alzheimer's disease but the underlying brain mechanisms have not been defined in patients directly. Here we addressed this issue in an Alzheimer's disease cohort using activation fMRI of two core musical memory systems. METHODS: We studied 34 patients with younger onset Alzheimer's disease led either by episodic memory decline (typical Alzheimer's disease) or by visuospatial impairment (posterior cortical atrophy) in relation to 19 age-matched healthy individuals. We designed a novel fMRI paradigm based on passive listening to melodies that were either previously familiar or unfamiliar (musical semantic memory) and either presented singly or repeated (incidental musical episodic memory). RESULTS: Both syndromic groups showed significant functional neuroanatomical alterations relative to the healthy control group. For musical semantic memory, disease-associated activation group differences were localised to right inferior frontal cortex (reduced activation in the group with memory-led Alzheimer's disease); while for incidental musical episodic memory, disease-associated activation group differences were localised to precuneus and posterior cingulate cortex (abnormally enhanced activation in the syndromic groups). In post-scan behavioural testing, both patient groups had a deficit of musical episodic memory relative to healthy controls whereas musical semantic memory was unimpaired. CONCLUSIONS: Our findings define functional neuroanatomical substrates for the differential involvement of musical semantic and incidental episodic memory in major phenotypes of Alzheimer's disease. The complex dynamic profile of brain activation group differences observed suggests that musical memory may be an informative probe of neural network function in Alzheimer's disease. These findings may guide the development of future musical interventions in dementia

Stratifying triple-negative breast cancer: which definition(s) to use?

Triple-negative breast cancers (TNBC) have increased rates of pathologic complete response following neoadjuvant chemotherapy, yet have poorer prognosis compared with non-TNBC. Known as the triple-negative paradox, this highlights the need to dissect the biologic and clinical heterogeneity within TNBC. In the present issue, Keam and colleagues suggest two subgroups of TNBC exist based on the proliferation-related marker Ki-67, each with differential response and prognosis following neoadjuvant chemotherapy. To place results into context, we review several definitions available under the TNBC umbrella that may stratify TNBC into clinically relevant subgroups

The development of a network for community-based obesity prevention: the CO-OPS Collaboration

Background: Community-based interventions are a promising approach and an important component of a comprehensive response to obesity. In this paper we describe the Collaboration of COmmunity-based Obesity Prevention Sites (CO-OPS Collaboration) in Australia as an example of a collaborative network to enhance the quality and quantity of obesity prevention action at the community level. The core aims of the CO-OPS Collaboration are to: identify and analyse the lessons learned from a range of community-based initiatives aimed at tackling obesity, and; to identify the elements that make community-based obesity prevention initiatives successful and share the knowledge gained with other communities.Methods: Key activities of the collaboration to date have included the development of a set of Best Practice Principles and knowledge translation and exchange activities to promote the application (or use) of evidence, evaluation and analysis in practice.Results: The establishment of the CO-OPS Collaboration is a significant step toward strengthening action in this area, by bringing together research, practice and policy expertise to promote best practice, high quality evaluation and knowledge translation and exchange. Future development of the network should include facilitation of furtherevidence generation and translation drawing from process, impact and outcome evaluation of existing communitybased interventions.Conclusions: The lessons presented in this paper may help other networks like CO-OPS as they emerge around the globe. It is important that networks integrate with each other and share the experience of creating these networks.<br /

Tracking of fatness during childhood, adolescence and young adulthood: a 7-year follow-up study in Madeira Island, Portugal

Aims: Investigating tracking of fatness from childhood to adolescence, early adolescence to young adulthood and late adolescence to young adulthood. Subjects and methods: Participants from the Madeira Growth Study were followed during an average period of 7.2 years. Height, body mass, skin-folds and circumferences were measured, nine health- and performance-related tests were administered and the Baecke questionnaire was used to assess physical activity. Skeletal maturity was estimated using the TW3 method. Results: The prevalence of overweight plus obesity ranged from 8.2–20.0% at baseline and from 20.4–40.0% at followup, in boys. Corresponding percentages for girls were 10.6– 12.0% and 13.2–18.0%. Inter-age correlations for fatness indicators ranged from 0.43–0.77. BMI, waist circumference and sum of skin-folds at 8, 12 and 16-years old were the main predictors of these variables at 15, 19 and 23-years old, respectively. Strength, muscular endurance and aerobic fitness were negatively related to body fatness. Physical activity and maturation were independently associated with adolescent (15 years) and young adult (19 years) fatness. Conclusions: Over 7.2 years, tracking was moderate-to-high for fatness. Variance was explained by fatness indicators and to a small extent by physical fitness, physical activity and maturation