Fenchel-Rockafellar type duality for a non-convex non-differential optimization problem

AbstractA Fenchel-Rockafellar type duality theorem is obtained for a non-convex and non-differentiable maximization problem by embedding the original problem in a family of perturbed problems. The recent results of Ivan Singer are developed in this more general framework. A relationship is also established between the solutions and optimal values of the primal and dual problems using the theory of subdifferential calculus

An Efficient Hybrid Fuzzy-Clustering Driven 3D-Modeling of Magnetic Resonance Imagery for Enhanced Brain Tumor Diagnosis

Brain tumor detection and its analysis are essential in medical diagnosis. The proposed work focuses on segmenting abnormality of axial brain MR DICOM slices, as this format holds the advantage of conserving extensive metadata. The axial slices presume the left and right part of the brain is symmetric by a Line of Symmetry (LOS). A semi-automated system is designed to mine normal and abnormal structures from each brain MR slice in a DICOM study. In this work, Fuzzy clustering (FC) is applied to the DICOM slices to extract various clusters for di erent k. Then, the best-segmented image that has high inter-class rigidity is obtained using the silhouette fitness function. The clustered boundaries of the tissue classes further enhanced by morphological operations. The FC technique is hybridized with the standard image post-processing techniques such as marker controlled watershed segmentation (MCW), region growing (RG), and distance regularized level sets (DRLS). This procedure is implemented on renowned BRATS challenge dataset of di erent modalities and a clinical dataset containing axial T2 weighted MR images of a patient. The sequential analysis of the slices is performed using the metadata information present in the DICOM header. The validation of the segmentation procedures against the ground truth images authorizes that the segmented objects of DRLS through FC enhanced brain images attain maximum scores of Jaccard and Dice similarity coe cients. The average Jaccard and dice scores for segmenting tumor part for ten patient studies of the BRATS dataset are 0.79 and 0.88, also for the clinical study 0.78 and 0.86, respectively. Finally, 3D visualization and tumor volume estimation are done using accessible DICOM information.Ministerio de Desarrollo de Recursos Humanos, India SPARC/2018-2019/P145/SLUniversidad Politécnica de Tomsk, Rusia RRSG/19/500

Case Series of Fertility Treatment in HIV-Discordant Couples (Male Positive, Female Negative): The Ontario Experience

The success of combination antiretroviral therapies for the treatment of human immunodeficiency virus (HIV) has resulted in prolonged life expectancy (over 40 years from diagnosis) and an improved quality of life for people living with HIV. The risk of vertical HIV transmission during pregnancy has been reduced to less than 1%. As a result of these breakthroughs and as many of these individuals are of reproductive age, fertility issues are becoming increasingly important for this population. One population in which conception planning and reduction of horizontal HIV transmission warrants further research is HIV-discordant couples where the male partner is HIV-positive and the female partner is HIV-negative. Sperm washing is a technique carried out in a fertility clinic that separates HIV from the seminal fluid. Although sperm washing followed by intrauterine insemination significantly reduces the risk of horizontal HIV transmission, there has been limited access to the procedure in North America. Furthermore, little is known about the conception decision-making experiences of HIV-discordant couples who might benefit from sperm washing. Chart reviews and semi-structured interviews were completed with 12 HIV-discordant couples in Ontario, Canada. Couples were recruited through HIV clinics and one fertility clinic that offered sperm washing. Participants identified a number of factors that affected their decision-making around pregnancy planning. Access to sperm washing and other fertility services was an issue (cost, travel and few clinics). Participants identified a lack of information on the procedure (availability, safety). Sources of support (social networks, healthcare providers) were unevenly distributed, especially among those who did not disclose their HIV status to friends and family. Finally, the stigmatisation of HIV continues to have a negative affect on HIV-discordant couples and their intentions to conceive. Access to sperm washing and fertility service is significantly limited for this population and is accompanied with a number of challenges

The bioenergetic signature of isogenic colon cancer cells predicts the cell death response to treatment with 3-bromopyruvate, iodoacetate or 5-fluorouracil

<p>Abstract</p> <p>Background</p> <p>Metabolic reprogramming resulting in enhanced glycolysis is a phenotypic trait of cancer cells, which is imposed by the tumor microenvironment and is linked to the down-regulation of the catalytic subunit of the mitochondrial H⁺-ATPase (β-F1-ATPase). The <it>bioenergetic signature </it>is a protein ratio (β-F1-ATPase/GAPDH), which provides an estimate of glucose metabolism in tumors and serves as a prognostic indicator for cancer patients. Targeting energetic metabolism could be a viable alternative to conventional anticancer chemotherapies. Herein, we document that the <it>bioenergetic signature </it>of isogenic colon cancer cells provides a gauge to predict the cell-death response to the metabolic inhibitors, 3-bromopyruvate (3BrP) and iodoacetate (IA), and the anti-metabolite, 5-fluorouracil (5-FU).</p> <p>Methods</p> <p>The <it>bioenergetic signature </it>of the cells was determined by western blotting. Aerobic glycolysis was determined from lactate production rates. The cell death was analyzed by fluorescence microscopy and flow cytometry. Cellular ATP concentrations were determined using bioluminiscence. Pearson's correlation coefficient was applied to assess the relationship between the <it>bioenergetic signature </it>and the cell death response. <it>In vivo </it>tumor regression activities of the compounds were assessed using a xenograft mouse model injected with the highly glycolytic HCT116 colocarcinoma cells.</p> <p>Results</p> <p>We demonstrate that the <it>bioenergetic signature </it>of isogenic HCT116 cancer cells inversely correlates with the potential to execute necrosis in response to 3BrP or IA treatment. Conversely, the <it>bioenergetic signature </it>directly correlates with the potential to execute apoptosis in response to 5-FU treatment in the same cells. However, despite the large differences observed in the <it>in vitro </it>cell-death responses associated with 3BrP, IA and 5-FU, the <it>in vivo </it>tumor regression activities of these agents were comparable.</p> <p>Conclusions</p> <p>Overall, we suggest that the determination of the <it>bioenergetic signature </it>of colon carcinomas could provide a tool for predicting the therapeutic response to various chemotherapeutic strategies aimed at combating tumor progression.</p

MCT1-mediated transport of a toxic molecule is an effective strategy for targeting glycolytic tumors

There is increasing evidence that oncogenic transformation modifies the metabolic program of cells. A common alteration is the upregulation of glycolysis, and efforts to target glycolytic enzymes for anticancer therapy are under way. Here, we performed a genome-wide haploid genetic screen to identify resistance mechanisms to 3-bromopyruvate (3-BrPA), a drug candidate that inhibits glycolysis in a poorly understood fashion. We identified the SLC16A1 gene product, MCT1, as the main determinant of 3-BrPA sensitivity. MCT1 is necessary and sufficient for 3-BrPA uptake by cancer cells. Additionally, SLC16A1 mRNA levels are the best predictor of 3-BrPA sensitivity and are most elevated in glycolytic cancer cells. Furthermore, forced MCT1 expression in 3-BrPA–resistant cancer cells sensitizes tumor xenografts to 3-BrPA treatment in vivo. Our results identify a potential biomarker for 3-BrPA sensitivity and provide proof of concept that the selectivity of cancer-expressed transporters can be exploited for delivering toxic molecules to tumors.National Institutes of Health (U.S.) (NIH CA103866)Jane Coffin Childs Memorial Fund for Medical Research (Fellowship)National Science Foundation (U.S.) (Fellowship)Howard Hughes Medical Institute (Investigator

My partner wants a child: A cross-sectional study of the determinants of the desire for children among mutually disclosed sero-discordant couples receiving care in Uganda

<p>Abstract</p> <p>Background</p> <p>The percentages of couples in HIV sero-discordant relationships range from 5 to 31% in the various countries of Africa. Given the importance of procreation and the lack of assisted reproduction to avoid partner transmission, members of these couples are faced with a serious dilemma even after the challenge of disclosing their HIV status to their spouses. Identifying the determinants of the decision to have children among sero-discordant couples will help in setting reproductive intervention priorities in resource-poor countries.</p> <p>Methods</p> <p>We conducted a survey among 114 mutually disclosed sero-discordant couples (228 individuals) receiving HIV care at four centres in Greater Kampala, between June and December 2007. The data we collected was classified according to whether the man or the woman was HIV-positive. We carried out multivariate logistic regression modelling to determine factors (age, gender, and the influences of relatives and of health workers, ART knowledge, and disclosure) that are independently associated with a desire for children.</p> <p>Results</p> <p>The majority, 59%, of the participants, desired to have children. The belief that their partner wanted children was a major determinant of the desire to have children, irrespective of the HIV sero-status (adjusted odds ratio 24.0 (95% CI 9.15, 105.4)). Among couples in which the woman was HIV-positive, young age and relatives' expectations for children were significantly associated with increased fertility desire, while among couples in which the man was positive; knowledge of ART effectiveness was associated with increased fertility desire. Availability of information on contraception was associated with decreased fertility desire.</p> <p>Conclusions</p> <p>The gender of the positive partner affects the factors associated with a desire for children. Interventions targeting sero-discordant couples should explore contraceptive choices, the cultural importance of children, and partner communication.</p