488 research outputs found
The effect of the annealing temperature on the local distortion of LaCaMnO thin films
Mn -edge fluorescence data are presented for thin film samples (3000~\AA)
of Colossal Magnetoresistive (CMR) LaCaMnO: as-deposited,
and post-annealed at 1000 K and 1200 K. The local distortion is analyzed in
terms of three contributions: static, phonon, and an extra,
temperature-dependent, polaron term. The polaron distortion is very small for
the as-deposited sample and increases with the annealing temperature. In
contrast, the static distortion in the samples decreases with the annealing
temperature. Although the local structure of the as-deposited sample shows very
little temperature dependence, the change in resistivity with temperature is
the largest of these three thin film samples. The as-deposited sample also has
the highest magnetoresistance (MR), which indicates some other mechanism may
also contribute to the transport properties of CMR samples. We also discuss the
relationship between local distortion and the magnetization of the sample.Comment: 11 pages of Preprint format, 8 figures in one tar fil
Mood and anxiety disorders in very preterm/very low-birth weight individuals from 6 to 26 years
Background
Very preterm (<32 weeks’ gestational age; VP) or very low–birth weight (<1,500 g; VLBW) birth has been associated with increased risk for anxiety and mood disorders and less partnering in adulthood. The aim was to test whether (a) VP/VLBW are at increased risk of any anxiety or mood disorders from 6 to 26 years compared with term-born individuals; (b) social support from romantic partners is associated with protection from anxiety and mood disorders; and (c) VP/VLBW adults’ lower social support mediates their risk for any anxiety and mood disorders.
Methods
Data are from a prospective geographically defined longitudinal whole-population study in South Bavaria (Germany). Two hundred VP/VLBW and 197 term individuals were studied from birth to adulthood. Anxiety and mood disorders were assessed at 6, 8, and 26 years with standardized diagnostic interviews and social support via self-report at age 26.
Results
At age 6, VP/VLBW children were not at increased risk of any anxiety or mood disorder. At age 8, VP/VLBW more often had any anxiety disorder than term comparisons (11.8% vs. 6.6%, OR = 2.10, 95% CI [1.08–4.10]). VP/VLBW adults had an increased risk for any mood (27.5% vs. 18.8%, OR = 1.65 [1.02–2.67]) but not for any anxiety disorder (33.0% vs. 28.4%, OR = 1.27 [0.82–1.96]). None of the significant differences survived correction for multiple testing. Social support was associated with a lower risk of anxiety or mood disorders in both groups (OR = 0.81 [0.68–0.96]) and mediated the association of VP/VLBW birth with any anxiety or any mood disorders at age 26.
Conclusions
This study does not show a persistently increased risk for any anxiety or mood disorder after VP/VLBW birth. Low social support from a romantic partner mediates the risk for anxiety or mood disorders after VP/VLBW birth
Development and evaluation of a de-identification procedure for a case register sourced from mental health electronic records
Background: Electronic health records (EHRs) provide enormous potential for health research but also present data governance challenges. Ensuring de-identification is a pre-requisite for use of EHR data without prior consent. The South London and Maudsley NHS Trust (SLaM), one of the largest secondary mental healthcare providers in Europe, has developed, from its EHRs, a de-identified psychiatric case register, the Clinical Record Interactive Search (CRIS), for secondary research. Methods: We describe development, implementation and evaluation of a bespoke de-identification algorithm used to create the register. It is designed to create dictionaries using patient identifiers (PIs) entered into dedicated source fields and then identify, match and mask them (with ZZZZZ) when they appear in medical texts. We deemed this approach would be effective, given high coverage of PI in the dedicated fields and the effectiveness of the masking combined with elements of a security model. We conducted two separate performance tests i) to test performance of the algorithm in masking individual true PIs entered in dedicated fields and then found in text (using 500 patient notes) and ii) to compare the performance of the CRIS pattern matching algorithm with a machine learning algorithm, called the MITRE Identification Scrubber Toolkit – MIST (using 70 patient notes – 50 notes to train, 20 notes to test on). We also report any incidences of potential breaches, defined by occurrences of 3 or more true or apparent PIs in the same patient’s notes (and in an additional set of longitudinal notes for 50 patients); and we consider the possibility of inferring information despite de-identification. Results: True PIs were masked with 98.8% precision and 97.6% recall. As anticipated, potential PIs did appear, owing to misspellings entered within the EHRs. We found one potential breach. In a separate performance test, with a different set of notes, CRIS yielded 100% precision and 88.5% recall, while MIST yielded a 95.1% and 78.1%, respectively. We discuss how we overcome the realistic possibility – albeit of low probability – of potential breaches through implementation of the security model. Conclusion: CRIS is a de-identified psychiatric database sourced from EHRs, which protects patient anonymity and maximises data available for research. CRIS demonstrates the advantage of combining an effective de-identification algorithm with a carefully designed security model. The paper advances much needed discussion of EHR de-identification – particularly in relation to criteria to assess de-identification, and considering the contexts of de-identified research databases when assessing the risk of breaches of confidential patient information
Cutoff for the Ising model on the lattice
Introduced in 1963, Glauber dynamics is one of the most practiced and
extensively studied methods for sampling the Ising model on lattices. It is
well known that at high temperatures, the time it takes this chain to mix in
on a system of size is . Whether in this regime there is
cutoff, i.e. a sharp transition in the -convergence to equilibrium, is a
fundamental open problem: If so, as conjectured by Peres, it would imply that
mixing occurs abruptly at for some fixed , thus providing
a rigorous stopping rule for this MCMC sampler. However, obtaining the precise
asymptotics of the mixing and proving cutoff can be extremely challenging even
for fairly simple Markov chains. Already for the one-dimensional Ising model,
showing cutoff is a longstanding open problem.
We settle the above by establishing cutoff and its location at the high
temperature regime of the Ising model on the lattice with periodic boundary
conditions. Our results hold for any dimension and at any temperature where
there is strong spatial mixing: For this carries all the way to the
critical temperature. Specifically, for fixed , the continuous-time
Glauber dynamics for the Ising model on with periodic boundary
conditions has cutoff at , where is
the spectral gap of the dynamics on the infinite-volume lattice. To our
knowledge, this is the first time where cutoff is shown for a Markov chain
where even understanding its stationary distribution is limited.
The proof hinges on a new technique for translating to mixing
which enables the application of log-Sobolev inequalities. The technique is
general and carries to other monotone and anti-monotone spin-systems.Comment: 34 pages, 3 figure
Feline mammary carcinoma stem cells are tumorigenic, radioresistant, chemoresistant and defective in activation of the ATM/p53 DNA damage pathway
AbstractCancer stem cells were identified in a feline mammary carcinoma cell line by demonstrating expression of CD133 and utilising the tumour sphere assay. A population of cells was identified that had an invasive, mesenchymal phenotype, expressed markers of pluripotency and enhanced tumour formation in the NOD-SCID mouse and chick embryo models. This population of feline mammary carcinoma stem cells was resistant to chemotherapy and radiation, possibly due to aberrant activation of the ATM/p53 DNA damage pathway. Epithelial–mesenchymal transition was a feature of the invasive phenotype. These data demonstrate that cancer stem cells are a feature of mammary cancer in cats
LCCC 1025: a phase II study of everolimus, trastuzumab, and vinorelbine to treat progressive HER2-positive breast cancer brain metastases
Purpose: HER2 + breast cancer (BC) is an aggressive subtype with high rates of brain metastases (BCBM). Two-thirds of HER2 + BCBM demonstrate activation of the PI3K/mTOR pathway driving resistance to anti-HER2 therapy. This phase II study evaluated everolimus (E), a brain-permeable mTOR inhibitor, trastuzumab (T), and vinorelbine (V) in patients with HER2 + BCBM. Patients and methods: Eligible patients had progressive HER2 + BCBM. The primary endpoint was intracranial response rate (RR); secondary objectives were CNS clinical benefit rate (CBR), extracranial RR, time to progression (TTP), overall survival (OS), and targeted sequencing of tumors from enrolled patients. A two-stage design distinguished intracranial RR of 5% versus 20%. Results: 32 patients were evaluable for toxicity, 26 for efficacy. Intracranial RR was 4% (1 PR). CNS CBR at 6 mos was 27%; at 3 mos 65%. Median intracranial TTP was 3.9 mos (95% CI 2.2–5). OS was 12.2 mos (95% CI 0.6–20.2). Grade 3–4 toxicities included neutropenia (41%), anemia (16%), and stomatitis (16%). Mutations in TP53 and PIK3CA were common in BCBM. Mutations in the PI3K/mTOR pathway were not associated with response. ERBB2 amplification was higher in BCBM compared to primary BC; ERBB2 amplification in the primary BC trended toward worse OS. Conclusion: While intracranial RR to ETV was low in HER2 + BCBM patients, one-third achieved CNS CBR; TTP/OS was similar to historical control. No new toxicity signals were observed. Further analysis of the genomic underpinnings of BCBM to identify tractable prognostic and/or predictive biomarkers is warranted. Clinical Trial: (NCT01305941)
An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics
For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types
Prophets vs. profits: How market competition influences leaders' disciplining behavior towards ethical transgressions
We investigate how market competition influences the way organizational leaders discipline moral transgressions of employees. In a cross-sectional study among organizational leaders at various hierarchical levels (Study 1), we find that strong market competition is related to an instrumental decision frame (business practices being perceived as focused on serving the organization’s interest). This decision frame explains why strong market competition is related to leaders’ perceptions of the evaluation of wrongdoing in terms of instrumental rather than moral concerns. In two subsequent experiments (Study 2 and 3), we find that high (relative to low) market competition makes leaders’ disciplining of moral transgressions contingent upon the instrumentality of the transgression to the organization. We find that the same transgression is punished less severely when it resulted in profit for the organization than when it resulted in loss. This research is among the first to identify conditions that determine the disciplinary responses of organization leaders to employees’ moral transgressions, and it feeds the debate on whether market competition - a fundamental characteristic of capitalist economies - promotes the display of moral or immoral behavior within organization
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