Nonlinear Ionic Conductivity of Thin Solid Electrolyte Samples: Comparison between Theory and Experiment

Nonlinear conductivity effects are studied experimentally and theoretically for thin samples of disordered ionic conductors. Following previous work in this field the {\it experimental nonlinear conductivity} of sodium ion conducting glasses is analyzed in terms of apparent hopping distances. Values up to 43 \AA are obtained. Due to higher-order harmonic current density detection, any undesired effects arising from Joule heating can be excluded. Additionally, the influence of temperature and sample thickness on the nonlinearity is explored. From the {\it theoretical side} the nonlinear conductivity in a disordered hopping model is analyzed numerically. For the 1D case the nonlinearity can be even handled analytically. Surprisingly, for this model the apparent hopping distance scales with the system size. This result shows that in general the nonlinear conductivity cannot be interpreted in terms of apparent hopping distances. Possible extensions of the model are discussed.Comment: 7 pages, 6 figure

Practical reasoning in political discourse: The UK government's response to the economic crisis in the 2008 Pre-Budget Report

This article focuses on practical reasoning in political discourse and argues for a better integration of argumentation theory with critical discourse analysis (CDA). Political discourse and its specific genres (for example, deliberation) primarily involve forms of practical reasoning, typically oriented towards finding solutions to problems and deciding on future courses of action. Practical reasoning is a form of inference from cognitive and motivational premises: from what we believe (about the situation or about means—end relations) and what we want or desire (our goals and values), leading to a normative judgement (and often a decision) concerning action. We offer an analysis of the main argument in the UK government’s 2008 Pre-Budget Report (HM Treasury, 2008) and suggest how a critical evaluation of the argument from the perspective of a normative theory of argumentation (particularly the informal logic developed by Douglas Walton) can provide the basis for an evaluation in terms of characteristic CDA concerns. We are advancing this analysis as a contribution to CDA, aimed at increasing the rigour and systematicity of its analyses of political discourse, and as a contribution to the normative concerns of critical social science

A Multidisciplinary Breast Cancer Brain Metastases Clinic: The University of North Carolina Experience

Breast cancer brain metastasis (BCBM) confers a poor prognosis and is unusual in requiring multidisciplinary care in the metastatic setting. The University of North Carolina at Chapel Hill (UNC-CH) has created a BCBM clinic to provide medical and radiation oncology, neurosurgical, and supportive services to this complex patient population. We describe organization and design of the clinic as well as characteristics, treatments, and outcomes of the patients seen in its first 3 years

Spinal intradural extraosseous Ewing's sarcoma

Extraosseous Ewing's sarcoma (EES) involving the central nervous system is rare, but can be diagnosed and distinguished from other primitive neuroectodermal tumors (PNET) by identification of the chromosomal translocation (11;22)(q24;q12). We report EES arising from the spinal intradural extramedullary space, based on imaging, histopathological, and molecular data in two men, ages 50 and 60 years old and a review of the literature using PubMed (1970–2009). Reverse transcriptase polymerase chain reaction (RT-PCR) identified the fusion product FL1-EWS. Multimodal therapy, including radiation and alternating chemotherapy including vincristine, cyclophosphamide, doxorubicin and ifosfamide and etoposide led to local tumor control and an initial, favorable therapeutic response. No systemic involvement was seen from the time of diagnosis to the time of last follow-up (26 months) or death (4 years). This report confirms that EES is not confined to the earliest decades of life, and like its rare occurrence as an extra-axial meningeal based mass intracranially, can occasionally present as an intradural mass in the spinal canal without evidence of systemic tumor. Gross total resection followed by multimodal therapy may provide for extended progression free and overall survival

A Study of the Day - Night Effect for the Super - Kamiokande Detector: I. Time Averaged Solar Neutrino Survival Probability

This is the first of two articles aimed at providing comprehensive predictions for the day-night (D-N) effect for the Super-Kamiokande detector in the case of the MSW \nu_e \to \numt transition solution of the solar neutrino problem. The one-year averaged probability of survival of the solar \nue crossing the Earth mantle, the core, the inner 2/3 of the core, and the (core + mantle) is calculated with high precision (better than 1%) using the elliptical orbit approximation (EOA) to describe the Earth motion around the Sun. Results for the survival probability in the indicated cases are obtained for a large set of values of the MSW transition parameters $\Delta m^2$ and $sin^22\theta_{V}$ from the ``conservative'' regions of the MSW solution, derived by taking into account possible relatively large uncertainties in the values of the $^{8}$B and $^{7}$Be neutrino fluxes. Our results show that the one-year averaged D-N asymmetry in the $\nu_e$ survival probability for neutrinos crossing the Earth core can be, in the case of $sin^22 \theta_{V} \leq 0.13$, larger than the asymmetry in the probability for (only mantle crossing + core crossing) neutrinos by a factor of up to six. The enhancement is larger in the case of neutrinos crossing the inner 2/3 of the core. This indicates that the Super-Kamiokande experiment might be able to test the $sin^22\theta_{V} \leq 0.01$ region of the MSW solution of the solar neutrino problem by performing selective D-N asymmetry measurements.Comment: LaTeX2e - 18 Text Pages + 21 figures = 39 Pages. - Figures in PS + text file sk1b14.tex requires two auxiliary files (included

Effect of a micronutrient-rich snack taken preconceptionally and throughout pregnancy on ultrasound measures of fetal growth: The Mumbai Maternal Nutrition Project (MMNP)

Improving micronutrient intakes of under‐nourished mothers in low‐ and middle‐income countries increases birth weight, but there is little data on the nature and timing during gestation of any effects on fetal growth. Ultrasound measures of fetal size were used to determine whether and when a food‐based supplement affected fetal growth. Non‐pregnant women living in Mumbai slums, India (N = 6,513), were randomly assigned to receive either a daily micronutrient‐rich snack containing green leafy vegetables, fruit, and milk (treatment) or a snack made from lower‐micronutrient vegetables (control) in addition to their usual diet from before pregnancy until delivery. From 2,291 pregnancies, the analysis sample comprised 1,677 fetuses (1,335 fetuses of women supplemented for ≥3 months before conception). First‐trimester (median: 10 weeks, interquartile range: 9–12 weeks) fetal crown‐rump length was measured. Fetal head circumference, biparietal diameter, femur length, and abdominal circumference were measured during the second (19, 19–20 weeks) and third trimesters (29, 28–30 weeks). The intervention had no effect on fetal size or growth at any stage of pregnancy. In the second trimester, there were interactions between parity and allocation group for biparietal diameter (p = .02) and femur length (p = .04) with both being smaller among fetuses of primiparous women and larger among those of multiparous women, in the treatment group compared with the controls. Overall, a micronutrient‐rich supplement did not increase standard ultrasound measures of fetal size and growth at any stage of pregnancy. Additional ultrasound measures of fetal soft tissues (fat and muscle) may be informative

Structural basis of phosphatidylinositol 3-kinase C2α function

Phosphatidylinositol 3-kinase type 2α (PI3KC2α) is an essential member of the structurally unresolved class II PI3K family with crucial functions in lipid signaling, endocytosis, angiogenesis, viral replication, platelet formation and a role in mitosis. The molecular basis of these activities of PI3KC2α is poorly understood. Here, we report high-resolution crystal structures as well as a 4.4-Å cryogenic-electron microscopic (cryo-EM) structure of PI3KC2α in active and inactive conformations. We unravel a coincident mechanism of lipid-induced activation of PI3KC2α at membranes that involves large-scale repositioning of its Ras-binding and lipid-binding distal Phox-homology and C-C2 domains, and can serve as a model for the entire class II PI3K family. Moreover, we describe a PI3KC2α-specific helical bundle domain that underlies its scaffolding function at the mitotic spindle. Our results advance our understanding of PI3K biology and pave the way for the development of specific inhibitors of class II PI3K function with wide applications in biomedicine

Structural basis of phosphatidylinositol 3-kinase C2α function

Phosphatidylinositol 3-kinase type 2α (PI3KC2α) is an essential member of the structurally unresolved class II PI3K family with crucial functions in lipid signaling, endocytosis, angiogenesis, viral replication, platelet formation and a role in mitosis. The molecular basis of these activities of PI3KC2α is poorly understood. Here, we report high-resolution crystal structures as well as a 4.4-Å cryogenic-electron microscopic (cryo-EM) structure of PI3KC2α in active and inactive conformations. We unravel a coincident mechanism of lipid-induced activation of PI3KC2α at membranes that involves large-scale repositioning of its Ras-binding and lipid-binding distal Phox-homology and C-C2 domains, and can serve as a model for the entire class II PI3K family. Moreover, we describe a PI3KC2α-specific helical bundle domain that underlies its scaffolding function at the mitotic spindle. Our results advance our understanding of PI3K biology and pave the way for the development of specific inhibitors of class II PI3K function with wide applications in biomedicine

A classification prognostic score to predict OS in stage IV well-differentiated neuroendocrine tumors

No validated prognostic tool is available for predicting overall survival (OS) of patients with well-differentiated neuroendocrine tumors (WDNETs). This study, conducted in three independent cohorts of patients from five different European countries, aimed to develop and validate a classification prognostic score for OS in patients with stage IV WDNETs. We retrospectively collected data on 1387 patients: (i) patients treated at the Istituto Nazionale Tumori (Milan, Italy; n = 515); (ii) European cohort of rare NET patients included in the European RARECAREnet database (n = 457); (iii) Italian multicentric cohort of pancreatic NET (pNETs) patients treated at 24 Italian institutions (n = 415). The score was developed using data from patients included in cohort (i) (training set); external validation was performed by applying the score to the data of the two independent cohorts (ii) and (iii) evaluating both calibration and discriminative ability (Harrell C statistic). We used data on age, primary tumor site, metastasis (synchronous vs metachronous), Ki-67, functional status and primary surgery to build the score, which was developed for classifying patients into three groups with differential 10-year OS: (I) favorable risk group: 10-year OS >= 70%; (II) intermediate risk group: 30% <= 10-year OS < 70%; (III) poor risk group: 10-year OS < 30%. The Harrell C statistic was 0.661 in the training set, and 0.626 and 0.601 in the RARECAREnet and Italian multicentric validation sets, respectively. In conclusion, based on the analysis of three 'field-practice' cohorts collected in different settings, we defined and validated a prognostic score to classify patients into three groups with different long-term prognoses

ATTAIN: Phase III study of etirinotecan pegol versus treatment of physician's choice in patients with metastatic breast cancer and brain metastases

The increasing incidence of breast cancer brain metastases is a major clinical problem with its associated poor prognosis and limited treatment options. The long-acting topoisomerase-1 inhibitor, etirinotecan pegol, was designed to preferentially accumulate in tumor tissue including brain metastases, providing sustained cytotoxic SN38 levels. Motivated by improved survival findings from subgroup analyses from the Phase III BEACON trial, this ongoing randomized, Phase III trial compares etirinotecan pegol to drugs commonly used for advanced breast cancer in patients with stable, treated breast cancer brain metastases who have been previously treated with an anthracycline, taxane and capecitabine. The primary end point is overall survival. Secondary end points include objective response rate, progression-free survival and time to CNS disease progression or recurrence in patients with/without CNS lesions present at study entry. Trial registration number: NCT02915744