757 research outputs found

    Almost Euclidean sections of the N-dimensional cross-polytope using O(N) random bits

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    It is well known that R^N has subspaces of dimension proportional to N on which the \ell_1 norm is equivalent to the \ell_2 norm; however, no explicit constructions are known. Extending earlier work by Artstein--Avidan and Milman, we prove that such a subspace can be generated using O(N) random bits.Comment: 16 pages; minor changes in the introduction to make it more accessible to both Math and CS reader

    Safety and Tolerability of PD‐1/PD‐L1 Inhibitors Compared with Chemotherapy in Patients with Advanced Cancer: A Meta‐Analysis

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    BACKGROUND: Compared with chemotherapy, significant improvement in survival outcomes with the programmed death receptor-1 (PD-1) inhibitors nivolumab and pembrolizumab and the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab has been shown in several types of advanced solid tumors. We conducted a systematic review and meta-analysis to compare safety and tolerability between PD-1/PD-L1 inhibitors and chemotherapy. METHODS: PubMed and American Society of Clinical Oncology (ASCO) databases were searched 1966 to September 2016. Eligible studies included randomized controlled trials (RCTs) comparing single-agent U.S. Food and Drug Administration-approved PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab, or atezolizumab) with chemotherapy in cancer patients reporting any all-grade (1-4) or high-grade (3-4) adverse events (AEs), all- or high-grade treatment-related symptoms, hematologic toxicities and immune-related AEs, treatment discontinuation due to toxicities, or treatment-related deaths. The summary incidence, relative risk, and 95% confidence intervals were calculated. RESULTS: A total of 3,450 patients from 7 RCTs were included in the meta-analysis: 4 nivolumab, 2 pembrolizumab, and 1 atezolizumab trials. The underlying malignancies included were non-small cell lung cancer (4 trials) and melanoma (3 trials). Compared with chemotherapy, the PD-1/PD-L1 inhibitors had a significantly lower risk of all- and high-grade fatigue, sensory neuropathy, diarrhea and hematologic toxicities, all-grade anorexia, nausea, and constipation, any all- and high-grade AEs, and treatment discontinuation. There was an increased risk of all-grade rash, pruritus, colitis, aminotransferase elevations, hypothyroidism, and hyperthyroidism, and all- and high-grade pneumonitis with PD1/PD-L1 inhibitors. CONCLUSION: PD-1/PD-L1 inhibitors are overall better tolerated than chemotherapy. Our results provide further evidence supporting the favorable risk/benefit ratio for PD-1/PD-L1 inhibitors. The Oncologist 2017;22:470-479 IMPLICATIONS FOR PRACTICE: We conducted a systematic review and meta-analysis to compare summary toxicity endpoints and clinically relevant adverse events between programmed death receptor-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors and chemotherapy. PD1/PD-L1 inhibitors were associated with a lower risk of treatment-related symptoms (fatigue, anorexia, nausea, diarrhea, constipation, and sensory neuropathy) but a higher risk of immune-related adverse events (AEs). Summary toxicity endpoints favor PD1/PD-L1 inhibitors (any all- and high-grade AEs and treatment discontinuation). PD1/PD-L1 inhibitors are overall better tolerated than chemotherapy. In addition to efficacy data from trials, our findings provide useful information for clinicians for well-balanced discussions with their patients on the risks and benefits of treatment options for advanced cancer

    Reconfigurable and non-volatile vertical magnetic logic gates

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    In this paper, we discuss the concept and prototype fabrication of reconfigurable and non-volatile vertical magnetic logic gates. These gates consist of two input layers and a RESET layer. The RESET layer allows the structure to be used as either an and or an or gate, depending on its magnetization state. To prove this concept, the gates were fabricated using a multi-layered patterned magnetic media, in which three magnetic layers are stacked and exchange-decoupled via non-magnetic interlayers. We demonstrate the functionality of these logic gates by conducting atomic force microscopy and magnetic force microscopy (MFM) analysis of the multi-layered patterned magnetic media. The logic gates operation mechanism and fabrication feasibility are both validated by the MFM imaging results

    Multidisciplinary Management of Breast Cancer During Pregnancy

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    Although breast cancer during pregnancy (BCDP) is rare (occurring with only 0.4% of all BC diagnoses in female patients aged 16–49 years), management decisions are challenging to both the patient and the multidisciplinary team

    Body Composition as a Predictor of Toxicity in Patients Receiving Anthracycline and Taxane–Based Chemotherapy for Early-Stage Breast Cancer

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    Poor body composition metrics (BCM) are associated with inferior cancer outcomes; however, in early breast cancer (EBC) there is a paucity of evidence regarding BCM’s impact on toxicities. This study investigates associations between BCM and treatment-related toxicity in EBC patients receiving anthracyclines-taxane based chemotherapy

    Skeletal Muscle Measures as Predictors of Toxicity, Hospitalization, and Survival in Patients with Metastatic Breast Cancer Receiving Taxane-Based Chemotherapy

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    Severe skeletal muscle (SM) loss (sarcopenia), is associated with poor cancer outcomes including reduced survival and increased toxicity. This study investigates SM measures in metastatic breast cancer (MBC) patients receiving first line taxane-based chemotherapy and evaluates associations with treatment toxicity and other outcomes

    Skeletal muscle measures and physical function in older adults with cancer: sarcopenia or myopenia?

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    BACKGROUND: Skeletal muscle loss, commonly known as sarcopenia, is highly prevalent in older adults and linked with adverse outcomes in cancer, yet the definition and role of sarcopenia remains uncertain. The aim of this study was to examine the association of Computerized Tomography (CT) assessed skeletal muscle measures with physical function in older adults with cancer. RESULTS: CTs for 185 patients were available. Median age 73 (IQR 68-76) and 56.5% female. After controlling for sex and BMI, we found no evidence that SMI was associated with physical function impairments. Both SMD and SMG were associated physical function impairments and higher values were associated with decreased limitations in instrumental activities of daily living (RR 0.84 [CI 0.73-0.96] and 0.94 [CI 0.89-0.99], respectively), climbing stairs (RR 0.84 [CI 0.76-0.94] and 0.91 [CI 0.87-0.96]), walking 1 block (RR 0.77 [CI 0.67-0.90] and 0.91 [CI 0.85-0.97]), and prolonged Timed Up and Go (RR 0.83 [CI 0.75-0.92] and 0.92 [CI 0.88-0.96]). MATERIALS AND METHODS: Using the Carolina Senior Registry, we identified patients with CT imaging performed within 60 days +/- of baseline geriatric assessment (GA). Skeletal muscle area and density (SMD) were analyzed from L3 lumbar segments. Muscle area and height (m2) were used to calculate skeletal muscle index (SMI). Skeletal Muscle Gauge (SMG) was created by multiplying SMI x SMD. CONCLUSIONS: Skeletal muscle mass as assessed from CT imaging was not associated with physical function impairments. Skeletal muscle radiodensity was more associated with physical function and may aid in identifying older adults at risk for functional impairments

    Management recommendations for pancreatic manifestations of von Hippel–Lindau disease

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    Von Hippel–Lindau disease (VHL) is a multineoplasm inherited disease manifesting with hemangioblastoma of the central nervous system and retina, adrenal pheochromocytoma, renal cell carcinoma, pancreatic neuroendocrine tumors and cysts, and neoplasms/cysts of the ear, broad ligament, and testicles. During 2018-2020, the VHL Alliance gathered several committees of experts in the various clinical manifestations of VHL to review the literature, gather the available evidence on VHL, and develop recommendations for patient management. The current report details the results of the discussion of a group of experts in the pancreatic manifestations of VHL along with their proposed recommendations for the clinical surveillance and management of patients with VHL. The recommendations subcommittee performed a comprehensive systematic review of the literature and conducted panel discussions to reach the current recommendations. The level of evidence was defined according to the Shekelle variation of the Grading of Recommendations, Assessment, Development, and Evaluation grading system. The National Comprehensive Cancer Network Categories of Evidence and Consensus defined the committee members' interpretation of the evidence and degree of consensus. The recommendations encompass the main aspects of VHL-related pancreatic manifestations and their clinical management. They are presented in a clinical orientation, including general planning of screening and surveillance for pancreatic neuroendocrine tumors, utility of biochemical biomarkers, the optimal choice for imaging modality, indirect risk stratification, indications for tissue sampling of VHL-related pancreatic neuroendocrine tumors, and interventions. These recommendations are designed to serve as the reference for all aspects of the screening, surveillance, and management of VHL-related pancreatic manifestations

    Biopsy of breast cancer metastases: patient characteristics and survival

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    Abstract Background Discordance in hormone receptors (HR) and human epidermal growth factor receptor 2 (HER2) status between primary tumors and metastatic sites for breast cancer is well established. However, it is uncertain which patient-related factors lead to biopsy when metastases are suspected and whether having a biopsy impacts survival. Methods The medical charts of metastatic breast cancer (MBC) patients diagnosed January 2000-August 2014 were retrospectively reviewed. A biopsy was defined as a procedure where tissue was obtained and assessed for both HR and HER2. Both bivariate and multivariate analyses were performed to assess patient characteristics related to biopsy and whether having a biopsy was associated with improved survival. Results Of 409 patients suspected of having MBC, 165 (40%) had a biopsy, and 34% of these had discordant HR or HER2 status when compared to the initial diagnosis. In multivariate analysis, having a biopsy was associated with: recurrence in years 2010–2014, disease-free interval of > =3 years, stage 0-IIA at presentation, suspected locoregional recurrence, being HR+/HER2-, or missing HR/HER2 at diagnosis. A similar multivariate analysis revealed that having a biopsy was associated with improved survival (HR = 0.67, p = 0.002). The association of biopsy and improved survival was noted in specific subgroups: patients with missing HR and HER2 data at initial diagnosis (p = 0.001), those without metastases in liver, lung or brain (p = 0.001), and being younger than 70 years old at recurrence (p < 0.001). Conclusions Specific clinical factors were associated with biopsy at the time of suspected recurrence. Having a biopsy was associated with reduced mortality

    Empowering minority women: Autonomy versus participation

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    Feminist attempts to empower women within their own cultural traditions have employed two broad strategies: authentic choice and participation. This paper argues that the methodological problems that beset the authentic choice strategy tell in favour of the participation approach. However, proponents of the participation strategy have failed to pay sufficient attention to the background conditions that need to be met if women are to make effective use of the institutional mechanisms their models advocate. If women are to be effective political agents at least some of the most serious structural inequalities that women face must be addressed. A nuanced statement of the participation strategy must therefore take account of long-standing feminist concerns regarding economic equality and access to resources. While this approach falls short of the demanding conditions for democratic citizenship implicit in the authentic choice strategy, it none the less places significant limits on the scope of participatory strategies and links the goal of empowering women within their own cultural traditions to wider feminist struggles to secure greater economic equality for women in general
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