Epicardial myocardial strain abnormalities may identify the earliest stages of arrhythmogenic cardiomyopathy.

The aim of this cohort study was to evaluate the value of echocardiographic multilayer strain analysis in the identification of arrhythmogenic cardiomyopathy (AC) in its earliest stages in which sudden cardiac death can occurs. Twenty seven asymptomatic relatives of AC probands (mean age 39.6 ± 19.5 years, 37 % male) with a desmosomal pathogenic mutation but no additional criteria for AC (group II) were compared to age and sex-matched healthy controls (group I). In addition, 70 patients harboring a pathogenic desmosomal mutation with "definitive" diagnosis of AC (group IV), and 19 subjects with "borderline" diagnosis (group III) were also studied. A standard echocardiographic evaluation plus left (LV) and right ventricular global and regional transmural, endocardial, and epicardial longitudinal strain (LS) analysis, was performed. In group II, while LV ejection fraction, fractional shortening, and S' were not significantly reduced compared to controls, transmural global LS was significantly reduced to 19.3 ± 1.8 % in group II versus 20.9 ± 1.1 % in controls (p = 0.0003). Compared to controls, group II presented significant (p < 0.05) regional LS decrease in the basal infero-lateral, antero-lateral, latero-apical, infero-septal, and septo-apical segments. Moreover, LS of the latero-apical and the basal antero-lateral segments was significantly altered in the epicardium (p < 0.05) but not significantly in the endocardium. Global and regional LV LS analysis allows detection of AC in an early or non-diagnostic stage of the disease. Moreover, epicardial LS analysis allows the detection of abnormalities earlier than endocardial LS

Dynamic programming with approximation function for nurse scheduling

Although dynamic programming could ideally solve any combinatorial optimization problem, the curse of dimensionality of the search space seriously limits its application to large optimization problems. For example, only few papers in the literature have reported the application of dynamic programming to workforce scheduling problems. This paper investigates approximate dynamic programming to tackle nurse scheduling problems of size that dynamic programming cannot tackle in practice. Nurse scheduling is one of the problems within workforce scheduling that has been tackled with a considerable number of algorithms particularly meta-heuristics. Experimental results indicate that approximate dynamic programming is a suitable method to solve this problem effectively

Markers for the identification of late breast cancer recurrence

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited

Evaluation of applying IHC4 as a prognostic model in the translational study of Intergroup Exemestane Study (IES): PathIES

Background: Intergroup Exemestane Study (IES) was a randomised study that showed a survival benefit of switching adjuvant endocrine therapy after 2–3 years from tamoxifen to exemestane. This PathIES aimed to assess the role of immunohistochemical (IHC)4 score in determining the relative sensitivity to either tamoxifen or sequential treatment with tamoxifen and exemestane. Patients and methods: Primary tumour samples were available for 1274 patients (27% of IES population). Only patients for whom the IHC4 score could be calculated (based on oestrogen receptor, progesterone receptor, HER2 and Ki67) were included in this analysis (N = 430 patients). The clinical score (C) was based on age, grade, tumour size and nodal status. The association of clinicopathological parameters, IHC4(+C) scores and treatment effect with time to distant recurrence-free survival (TTDR) was assessed in univariable and multivariable Cox regression analyses. A modified clinical score (PathIEscore) (N = 350) was also estimated. Results: Our results confirm the prognostic importance of the original IHC4, alone and in conjunction with clinical scores, but no significant difference with treatment effects was observed. The combined IHC4 + Clinical PathIES score was prognostic for TTDR (P < 0.001) with a hazard ratio (HR) of 5.54 (95% CI 1.29–23.70) for a change from 1st quartile (Q1) to Q1–Q3 and HR of 15.54 (95% CI 3.70–65.24) for a change from Q1 to Q4. Conclusion: In the PathIES population, the IHC4 score is useful in predicting long-term relapse in patients who remain disease-free after 2–3 years. This is a first trial to suggest the extending use of IHC4+C score for prognostic indication for patients who have switched endocrine therapies at 2–3 years and who remain disease-free after 2–3 years

Finger dexterity in well-functioning cohort of office workers in Macau

Aim: The study aimed to describe the finger dexterity in office workers of an Asian population. Methods: One hundred twenty-seven right-handed office workers, aged 21–50 with a similar split of male and female, were recruited with finger dexterity measured by the O’Connor Finger Dexterity Test. The grip strength, tip and lateral pinch strength of both hands were also measured. Results: This study provided the percentile score of the O’Connor Finger Dexterity Test of both males and females in the Asian population. Raw scores of below 218 and 213 seconds in male and female participants respectively reach the 90th percentile, and above 237 and 235 seconds in male and female below the 10th percentile. Results showed no significant difference in local mean scores across different age groups, between male and female and with varying hours of working in typing, filing, and writing. A significant difference was only found in finger dexterity and years of working as office workers. No significant correlation was found between the finger dexterity with grip strength, tip and lateral pinch of the dominant right hand. The results were similar to the original normative score with similar work skills and demands. Conclusion: The mean scores could be used as a valid reference for local occupational therapists to evaluate the finger dexterity of office workers. However, caution has to be taken that conclusions drawn can be biased because of the relatively small sample size, and the results cannot be generalized to represent a wider Asian population

The clinical and functional significance of c-Met in breast cancer: a review

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.CMH-Y is funded by a Cancer Research UK Clinical Research Fellowship. JLJ is funded by the Breast Cancer Campaign Tissue Bank

Biomarkers characterization of circulating tumour cells in breast cancer patients

Introduction: Increasing evidence supports the view that the detection of circulating tumor cells (CTCs) predicts outcomes of nonmetastatic breast cancer patients. CTCs differ genetically from the primary tumor and may contribute to variations in prognosis and response to therapy. As we start to understand more about the biology of CTCs, we can begin to address how best to treat this form of disease. Methods: Ninety-eight nonmetastatic breast cancer patients were included in this study. CTCs were isolated by immunomagnetic techniques using magnetic beads labelled with a multi-CK-specific antibody (CK3-11D5) and CTC detection through immunocytochemical methods. Estrogen receptor, progesterone receptor and epidermal growth factor receptor (EGFR) were evaluated by immunofluorescence experiments and HER2 and TOP2A by fluorescence in situ hybridization. We aimed to characterize this set of biomarkers in CTCs and correlate it with clinical-pathological characteristics. Results: Baseline detection rate was 46.9% ≥ 1 CTC/30 ml threshold. CTC-positive cells were more frequent in HER2-negative tumors (p = 0.046). In patients younger than 50 years old, HER2-amplified and G1-G2 tumors had a higher possibility of being nondetectable CTCs. Heterogeneous expression of hormonal receptors (HRs) in samples from the same patients was found. Discordances between HR expression, HER2 and TOP2A status in CTCs and their primary tumor were found in the sequential blood samples. Less that 35% of patients switched their CTC status after receiving chemotherapy. EGFR-positive CTCs were associated with Luminal tumors (p = 0.03). Conclusions: This is the largest exploratory CTC biomarker analysis in nonmetastatic BC patients. Our study suggests that CTC biomarkers profiles might be useful as a surrogate marker for therapeutic selection and monitoring since heterogeneity of the biomarker distribution in CTCs and the lack of correlation with the primary tumor biomarker status were found. Further exploration of the association between EGFR-positive CTCs and Luminal tumors is warranted

Obesity-Related Oxidative Stress: the Impact of Physical Activity and Diet Manipulation

Obesity-related oxidative stress, the imbalance between pro-oxidants and antioxidants (e.g., nitric oxide), has been linked to metabolic and cardiovascular disease, including endothelial dysfunction and atherosclerosis. Reactive oxygen species (ROS) are essential for physiological functions including gene expression, cellular growth, infection defense, and modulating endothelial function. However, elevated ROS and/or diminished antioxidant capacity leading to oxidative stress can lead to dysfunction. Physical activity also results in an acute state of oxidative stress. However, it is likely that chronic physical activity provides a stimulus for favorable oxidative adaptations and enhanced physiological performance and physical health, although distinct responses between aerobic and anaerobic activities warrant further investigation. Studies support the benefits of dietary modification as well as exercise interventions in alleviating oxidative stress susceptibility. Since obese individuals tend to demonstrate elevated markers of oxidative stress, the implications for this population are significant. Therefore, in this review our aim is to discuss (i) the role of oxidative stress and inflammation as associated with obesity-related diseases, (ii) the potential concerns and benefits of exercise-mediated oxidative stress, and (iii) the advantageous role of dietary modification, including acute or chronic caloric restriction and vitamin D supplementation

Heterocellular gene signatures reveal luminal-A breast cancer heterogeneity and differential therapeutic responses.

Breast cancer is a highly heterogeneous disease. Although differences between intrinsic breast cancer subtypes have been well studied, heterogeneity within each subtype, especially luminal-A cancers, requires further interrogation to personalize disease management. Here, we applied well-characterized and cancer-associated heterocellular signatures representing stem, mesenchymal, stromal, immune, and epithelial cell types to breast cancer. This analysis stratified the luminal-A breast cancer samples into five subtypes with a majority of them enriched for a subtype (stem-like) that has increased stem and stromal cell gene signatures, representing potential luminal progenitor origin. The enrichment of immune checkpoint genes and other immune cell types in two (including stem-like) of the five heterocellular subtypes of luminal-A tumors suggest their potential response to immunotherapy. These immune-enriched subtypes of luminal-A tumors (containing only estrogen receptor positive samples) showed good or intermediate prognosis along with the two other differentiated subtypes as assessed using recurrence-free and distant metastasis-free patient survival outcomes. On the other hand, a partially differentiated subtype of luminal-A breast cancer with transit-amplifying colon-crypt characteristics showed poor prognosis. Furthermore, published luminal-A subtypes associated with specific somatic copy number alterations and mutations shared similar cellular and mutational characteristics to colorectal cancer subtypes where the heterocellular signatures were derived. These heterocellular subtypes reveal transcriptome and cell-type based heterogeneity of luminal-A and other breast cancer subtypes that may be useful for additional understanding of the cancer type and potential patient stratification and personalized medicine