586 research outputs found

    Exploring the ā€˜middle groundā€™ between state and market: the example of China

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    Studies of housing systems lying in the ā€˜middle groundā€™ between state and market are subject to three important shortcomings. First, the widely used Esping-Andersen (EA) approach assesses only a subset of the key housing outcomes and may be less helpful for describing changes in housing policy regimes. Second, there is too much emphasis on tenure transitions, and an assumed close correspondence between tenure labels and effective system functioning may not be valid. Third, due attention has not been given to the spatial dimensions in which housing systems operate, in particular when housing policies have a significant devolved or localised emphasis. Updating EAā€™s framework, we suggest a preliminary list of housing system indicators in order to capture the nature of the housing systems being developed and devolved. We verified the applicability of this indicator system with the case of China. This illustrates clearly the need for a more nuanced and systematic basis for categorising differences and changes in welfare and housing policies

    Genome-wide CRISPR Screen in a Mouse Model of Tumor Growth and Metastasis

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    Genetic screens are powerful tools for identifying genes responsible for diverse phenotypes. Here we describe a genome-wide CRISPR/Cas9-mediated loss-of-function screen in tumor growth and metastasis. We mutagenized a non-metastatic mouse cancer cell line using a genome-scale library with 67,405 single-guide RNAs (sgRNAs). The mutant cell pool rapidly generates metastases when transplanted into immunocompromised mice. Enriched sgRNAs in lung metastases and late-stage primary tumors were found to target a small set of genes, suggesting that specific loss-of-function mutations drive tumor growth and metastasis. Individual sgRNAs and a small pool of 624 sgRNAs targeting the top-scoring genes from the primary screen dramatically accelerate metastasis. In all of these experiments, the effect of mutations on primary tumor growth positively correlates with the development of metastases. Our study demonstrates Cas9-based screening as a robust method to systematically assay gene phenotypes in cancer evolution in vivo.National Institutes of Health (U.S.) (Grant R01-CA133404)National Cancer Institute (U.S.) (Grant U54 CA151884)National Cancer Institute (U.S.) (Grant P30-CA14051)National Institute of Mental Health (U.S.) (Grant 5DP1-MH100706)National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (Grant 5R01-DK097768

    Analysis on the clinical features of 22 basaloid squamous cell carcinoma of the lung

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    <p>Abstract</p> <p>Background</p> <p>Basaloid squamous cell carcinoma of the lung is a rare and highly malignant tumor mostly observed in the proximal bronchi. Basaloid squamous cell carcinoma of the lung cases typically show rapid clinical progression, very poor prognosis and special pathological morphology. This project aimed to examine the clinical features of basaloid squamous cell carcinoma of the lung and the factors related to its prognosis; and to compare survival outcomes between basaloid squamous cell carcinoma and poorly differentiated squamous cell carcinomas (PDSC).</p> <p>Methods</p> <p>Between January 2004 and December 2008, pathological sections from basaloid squamous cell carcinoma and PDSC of the lung were collected and retrospectively analyzed at Tianjin Medical University Cancer Institute and Hospital. Data analysis was performed using Statistical Package for the Social Sciences (SPSS11.0). The Kaplan-Meier method was used to calculate the survival rate. Log-rank test was used to compare the differences in survival rate between the two groups. The factors influencing prognosis were analyzed using the Cox proportional hazard model.</p> <p>Results</p> <p>A total of 120 pathological sections were used in the analysis of this study-22 from basaloid squamous cell carcinoma cases and 98 from PDSC cases. Compared to the PDSC group, the basaloid squamous cell carcinoma group had a larger proportion of female patients (p = 0.001); however it had higher proportion of male smokers (p = 0.003). There were no statistically significant differences in survival rate between the two groups (Ļ‡<sup>2 </sup>= 1.200, p = 0.273). Additionally, prognosis of basaloid squamous cell carcinoma is significantly influenced by treatment mode and clinical stages of the tumor. The post-operation mortality hazard of patients treated with a combination chemotherapy and radiotherapy was 1.296 times higher than other treatment modes (<it>p </it>= 0.025). Increases in post-operation mortality hazard ratio were also associated with more advanced clinical stage of tumors (Ļ‡<sup>2 </sup>trend = 11.907, <it>p </it>= 0.000).</p> <p>Conclusions</p> <p>This study demonstrated that basaloid squamous cell carcinoma and PDSC have very similar clinical features, and there are no significant differences in survival rates between the two groups. Hence, we conclude that in the short term, the same clinical treatments and therapeutic modes can be administered to patients with basaloid squamous cell carcinoma and PDSC of the lung.</p

    Establishing the feasibility of the dosimetric compliance criteria of RTOG 1308: phase III randomized trial comparing overall survival after photon versus proton radiochemotherapy for inoperable stage II-IIIB NSCLC.

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    BACKGROUND: To establish the feasibility of the dosimetric compliance criteria of the RTOG 1308 trial through testing against Intensity Modulation Radiation Therapy (IMRT) and Passive Scattering Proton Therapy (PSPT) plans. METHODS: Twenty-six lung IMRT and 26 proton PSPT plans were included in the study. Dose Volume Histograms (DVHs) for targets and normal structures were analyzed. The quality of IMRT plans was assessed using a knowledge-based engineering tool. RESULTS: Most of the RTOG 1308 dosimetric criteria were achieved. The deviation unacceptable rates were less than 10 % for most criteria; however, a deviation unacceptable rate of more than 20 % was computed for the planning target volume minimum dose compliance criterion. Dose parameters for the target volume were very close for the IMRT and PSPT plans. However, the PSPT plans led to lower dose values for normal structures. The dose parameters in which PSPT plans resulted in lower values than IMRT plans were: lung V5Gy (%) (34.4 in PSPT and 47.2 in IMRT); maximum spinal cord dose (31.7 Gy in PSPT and 43.5 Gy in IMRT); heart V5Gy (%) (19 in PSPT and 47 in IMRT); heart V30Gy (%) (11 in PSPT and 19 in IMRT); heart V45Gy (%) (7.8 in PSPT and 12.1 in IMRT); heart V50% (Gy) (7.1 in PSPT and 9.8 in IMRT) and mean heart dose (7.7 Gy in PSPT and 14.9 Gy in IMRT). CONCLUSIONS: The revised RTOG 1308 dosimetric compliance criteria are feasible and achievable

    Toll-like receptor signaling adapter proteins govern spread of neuropathic pain and recovery following nerve injury in male mice.

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    BackgroundSpinal Toll-like receptors (TLRs) and signaling intermediaries have been implicated in persistent pain states. We examined the roles of two major TLR signaling pathways and selected TLRs in a mononeuropathic allodynia.MethodsL5 spinal nerve ligation (SNL) was performed in wild type (WT, C57BL/6) male and female mice and in male Tlr2-/-Tlr3-/-, Tlr4-/-, Tlr5-/-, Myd88-/-, Triflps2, Myd88/Triflps2, Tnf-/-, and Ifnar1-/- mice. We also examined L5 ligation in Tlr4-/- female mice. We examined tactile allodynia using von Frey hairs. Iba-1 (microglia) and GFAP (astrocytes) were assessed in spinal cords by immunostaining. Tactile thresholds were analyzed by 1- and 2-way ANOVA and the Bonferroni post hoc test was used.ResultsIn WT male and female mice, SNL lesions resulted in a persistent and robust ipsilateral, tactile allodynia. In males with TLR2, 3, 4, or 5 deficiencies, tactile allodynia was significantly, but incompletely, reversed (approximately 50%) as compared to WT. This effect was not seen in female Tlr4-/- mice. Increases in ipsilateral lumbar Iba-1 and GFAP were seen in mutant and WT mice. Mice deficient in MyD88, or MyD88 and TRIF, showed an approximately 50% reduction in withdrawal thresholds and reduced ipsilateral Iba-1. In contrast, TRIF and interferon receptor null mice developed a profound ipsilateral and contralateral tactile allodynia. In lumbar sections of the spinal cords, we observed a greater increase in Iba-1 immunoreactivity in the TRIF-signaling deficient mice as compared to WT, but no significant increase in GFAP. Removing MyD88 abrogated the contralateral allodynia in the TRIF signaling-deficient mice. Conversely, IFNĪ², released downstream to TRIF signaling, administered intrathecally, temporarily reversed the tactile allodynia.ConclusionsThese observations suggest a critical role for the MyD88 pathway in initiating neuropathic pain, but a distinct role for the TRIF pathway and interferon in regulating neuropathic pain phenotypes in male mice

    Discontinuous Galerkin methods for nonlinear scalar hyperbolic conservation laws: divided difference estimates and accuracy enhancement

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    In this paper, an analysis of the accuracy-enhancement for the discontinuous Galerkin (DG) method applied to one-dimensional scalar nonlinear hyperbolic conservation laws is carried out. This requires analyzing the divided difference of the errors for the DG solution. We therefore first prove that the alpha-th order (1 <= \alpha <= k+1) divided difference of the DG error in the L2-norm is of order k+(3-alpha)/2 when upwind fluxes are used, under the condition that |f'(u)| possesses a uniform positive lower bound. By the duality argument, we then derive superconvergence results of order k+(3-alpha)/2 in the negative-order norm, demonstrating that it is possible to extend the Smoothness-Increasing Accuracy-Conserving filter to nonlinear conservation laws to obtain at least (3k/2+1)th order superconvergence for post-processed solutions. As a by-product, for variable coefficient hyperbolic equations, we provide an explicit proof for optimal convergence results of order k+1 in the L2-norm for the divided differences of DG errors and thus (2k+1)th order superconvergence in negative-order norm holds. Numerical experiments are given that confirm the theoretical results

    Estimating prevalence of overweight and obesity at the neighborhood level: the value of maternal height and weight data available on birth certificate records

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    <p>Abstract</p> <p>Objective</p> <p>To determine the value of maternal height and weight data on birth certificate records when estimating prevalence of overweight and obese adults at the neighborhood level.</p> <p>Research Design and Methods</p> <p>Regression analysis was used to determine how much variation in the percentage of the adult population with a body mass index (BMI) of ā‰„ 25 (based on survey data) could be accounted for by the percentage of mothers with BMI ā‰„ 25 (based on birth certificate data) -- alone and in combination with other sociodemographic characteristics of census tracts.</p> <p>Results</p> <p>Alone, the percentage of mothers with BMI ā‰„ 25 explained more than half (R<sup>2 </sup>= .52) of the variation in the percentage of all residents in census tracts with BMI ā‰„ 25; in combination with several measures of the sociodemographic characteristics of the census tracts, 75% ( R<sup>2 </sup>= 75.2) of the variation is explained.</p> <p>Conclusions</p> <p>Maternal height and weight data available from birth certificate records may be useful for identifying neighborhoods with relatively high or low prevalence of adult residents who are overweight or obese. This is especially true if used in combination with readily available census data.</p

    Spectroscopic scanning tunneling microscopy insights into Fe-based superconductors

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    In the first three years since the discovery of Fe-based high Tc superconductors, scanning tunneling microscopy (STM) and spectroscopy have shed light on three important questions. First, STM has demonstrated the complexity of the pairing symmetry in Fe-based materials. Phase-sensitive quasiparticle interference (QPI) imaging and low temperature spectroscopy have shown that the pairing order parameter varies from nodal to nodeless s\pm within a single family, FeTe1-xSex. Second, STM has imaged C4 -> C2 symmetry breaking in the electronic states of both parent and superconducting materials. As a local probe, STM is in a strong position to understand the interactions between these broken symmetry states and superconductivity. Finally, STM has been used to image the vortex state, giving insights into the technical problem of vortex pinning, and the fundamental problem of the competing states introduced when superconductivity is locally quenched by a magnetic field. Here we give a pedagogical introduction to STM and QPI imaging, discuss the specific challenges associated with extracting bulk properties from the study of surfaces, and report on progress made in understanding Fe-based superconductors using STM techniques.Comment: 36 pages, 23 figures, 229 reference

    Modern microwave methods in solid state inorganic materials chemistry: from fundamentals to manufacturing

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