identifying patients with relapsing remitting multiple sclerosis using algorithms applied to us integrated delivery network healthcare data

Abstract Background Relapsing-remitting multiple sclerosis (RRMS) has a major impact on affected patients; therefore, improved understanding of RRMS is important, particularly in the context of real-world evidence. Objectives To develop and validate algorithms for identifying patients with RRMS in both unstructured clinical notes found in electronic health records (EHRs) and structured/coded health care claims data. Methods US Integrated Delivery Network data (2010–2014) were queried for study inclusion criteria (possible multiple sclerosis [MS] base cohort): one or more MS diagnosis code, patients aged 18 years or older, 1 year or more baseline history, and no other demyelinating diseases. Sets of algorithms were developed to search narrative text of unstructured clinical notes (EHR clinical notes–based algorithms) and structured/coded data (claims-based algorithms) to identify adult patients with RRMS, excluding patients with evidence of progressive MS. Medical records were reviewed manually for algorithm validation. Positive predictive value was calculated for both EHR clinical notes–based and claims-based algorithms. Results From a sample of 5308 patients with possible MS, 837 patients with RRMS were identified using only the EHR clinical notes–based algorithms and 2271 patients were identified using only the claims-based algorithms; 779 patients were identified using both algorithms. The positive predictive value was 99.1% (95% confidence interval [CI], 94.2%–100%) for the EHR clinical notes–based algorithms and 94.6% (95% CI, 89.1%–97.8%) to 94.9% (95% CI, 89.8%–97.9%) for the claims-based algorithms. Conclusions The algorithms evaluated in this study identified a real-world cohort of patients with RRMS without evidence of progressive MS that can be studied in clinical research with confidence

How much collocation knowledge do L2 learners have?: the effects of frequency and amount of exposure

Many scholars believe that collocations are difficult to learn and use by L2 learners. However, some research suggests that learners often know more collocations than commonly thought. This study tested 108 Spanish learners of English to measure their productive knowledge of 50 collocations, which varied according to corpus frequency, t-score, and MI score. The participants produced a mean score of 56.6% correct, suggesting that our learners knew a substantial number of collocations. Knowledge of the collocations correlated moderately with corpus frequency (.45), but also with everyday engagement with English outside the classroom, in activities like reading, watching movies/TV, and social networking (composite correlation = .56). Everyday engagement also had a stronger relationship with collocation knowledge than years of English study (.45)

Language and learning science in South Africa

South Africa is a multilingual country with 11 official languages. However, English dominates as the language of access and power and although the Language-in- Education Policy (1997) recommends school language policies that will promote additive bilingualism and the use of learners' home languages as languages of learning and teaching, there has been little implementation of these recommendations by schools. This is despite the fact that the majority of learners do not have the necessary English language proficiency to successfully engage with the curriculum and that teachers frequently are obliged to resort to using the learners' home language to mediate understanding. This research investigates the classroom language practices of six Grade 8 science teachers, teaching science through the medium of English where they and their learners share a common home language, Xhosa. Teachers' lessons were videotaped, transcribed and analysed for the opportunities they offered learners for language development and conceptual challenge. The purpose of the research is to better understand the teachers' perceptions and problems and to be able to draw on examples of good practice, to inform teacher training and to develop a coherent bilingual approach for teaching science through the medium of English as an additional language

Formulaic sequence (FS) cannot be an umbrella term in SLA : Focusing on psycholinguistic FSs and their identification

The term formulaic sequence (FS) is used with a multiplicity of meanings in the SLA literature, some overlapping but others not, and researchers are not always clear in defining precisely what they are investigating, or in limiting the implicational domain of their findings to the type of formulaicity they focus on. The first part of the article provides a conceptual framework focusing on the contrast between linguistic or learner-external definitions, that is, what is formulaic in the language the learner is exposed to, such as idiomatic expressions or collocations, and psycholinguistic or learner-internal definitions, that is, what is formulaic within an individual learner because it presents a processing advantage. The second part focuses on the methodological consequences of adopting a learner-internal approach to the investigation of FSs, and examines the challenges presented by the identification of psycholinguistic formulaicity in advanced L2 learners, proposing a tool kit based on a hierarchical identification method

H3K9 Methyltransferases and Demethylases Control Lung Tumor-Propagating Cells and Lung Cancer Progression

Epigenetic regulators are attractive anticancer targets, but the promise of therapeutic strategies inhibiting some of these factors has not been proven in vivo or taken into account tumor cell heterogeneity. Here we show that the histone methyltransferase G9a, reported to be a therapeutic target in many cancers, is a suppressor of aggressive lung tumor-propagating cells (TPCs). Inhibition of G9a drives lung adenocarcinoma cells towards the TPC phenotype by de-repressing genes which regulate the extracellular matrix. Depletion of G9a during tumorigenesis enriches tumors in TPCs and accelerates disease progression metastasis. Depleting histone demethylases represses G9a-regulated genes and TPC phenotypes. Demethylase inhibition impairs lung adenocarcinoma progression in vivo. Therefore, inhibition of G9a is dangerous in certain cancer contexts, and targeting the histone demethylases is a more suitable approach for lung cancer treatment. Understanding cellular context and specific tumor populations is critical when targeting epigenetic regulators in cancer for future therapeutic development

The Hierarchical Structure and Dynamics of Voids

Contrary to the common view voids have very complex internal structure and dynamics. Here we show how the hierarchy of structures in the density field inside voids is reflected by a similar hierarchy of structures in the velocity field. Voids defined by dense filaments and clusters can de described as simple expanding domains with coherent flows everywhere except at their boundaries. At scales smaller that the void radius the velocity field breaks into expanding sub-domains corresponding to sub- voids. These sub-domains break into even smaller sub-sub domains at smaller scales resulting in a nesting hierarchy of locally expanding domains. The ratio between the magnitude of the velocity field responsible for the expansion of the void and the velocity field defining the sub voids is approximately one order of magnitude. The small-scale components of the velocity field play a minor role in the shaping of the voids but they define the local dynamics directly affecting the processes of galaxy formation and evolution. The super-Hubble expansion inside voids makes them cosmic magnifiers by stretching their internal primordial density fluctuations allowing us to probe the small scales in the primordial density field. Voids also act like time machines by "freezing" the development of the medium-scale density fluctuations responsible for the formation of the tenuous web of structures seen connecting proto galaxies in computer simulations. As a result of this freezing haloes in voids can remain "connected" to this tenuous web until the present time. This may have an important effect in the formation and evolution of galaxies in voids by providing an efficient gas accretion mechanism via coherent low-velocity streams that can keep a steady inflow of matter for extended periods of time.Comment: High-res version are related media here: http://skysrv.pha.jhu.edu/~miguel/Papers/Hierarchy_voids/index.htm

Great Aunt Edna's vase: metaphor use in working with heritage language families

This article explores the use of a particular metaphor—Great Aunt Edna’s Vase—as a means to facilitating multilingual families in contextualizing and engaging with complex emotional connections as linked to language, identity, and belonging. Building from the premise that language is linked to the construction of identity, but that individual family members will have different views and opinions on the heritage language within this context, this article highlights the use of metaphors in family work, before introducing the metaphor of Great Aunt Edna’s Vase and situating it in relevant literature around language, heritage, and identity. The concepts introduced add to the existing body of literature in addressing the growing need for work specifically aimed at multilingual families, in a globally ever-more-diverse society, highlighting the links between language and well-being, and making a contribution to the global knowledge necessary for practitioners and families to explore these links successfully

Neuroanatomical Comparison of the “Word” and “Picture” Versions of the Free and Cued Selective Reminding Test in Alzheimer’s Disease

Episodic memory tests with cued recall, such as the Free and Cued Selective Reminding Test (FCSRT), allow for the delineation of hippocampal and prefrontal atrophy contributions to memory performance in Alzheimer’s disease (AD). Both Word and Picture versions of the test exist but show different profiles, with the Picture version usually scoring higher across different cohorts. One possible explanation for this divergent performance between the different modality versions of the test might be that they rely on different sets of neural correlates. The current study explores this by contrasting the neural correlates of the Word and Picture versions of the FCSRT with voxel-based morphometry (VBM) in AD and healthy subjects. We predicted that the Picture version would be associated with different cortical regions than the Word version, which might be more hippocampal-centric. When comparing 35 AD patients and 34 controls, AD patients exhibited impairments on both versions of the FCSRT and both groups performed higher in the Picture version. A region of interest analysis based on prior work revealed significant correlations between free recall of either version with atrophy of the temporal pole and hippocampal regions. Thus, contrary to expectations, performance on both the Word and the Picture version of the FCSRT is associated with largely overlapping networks. Free recall is associated with hippocampal volume and might be properly considered as an indicator of hippocampal structural integrity

Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer

As a master regulator of chromatin function, the lysine methyltransferase EZH2 orchestrates transcriptional silencing of developmental gene networks. Overexpression of EZH2 is commonly observed in human epithelial cancers, such as non-small cell lung carcinoma (NSCLC), yet definitive demonstration of malignant transformation by deregulated EZH2 remains elusive. Here, we demonstrate the causal role of EZH2 overexpression in NSCLC with new genetically-engineered mouse models of lung adenocarcinoma. Deregulated EZH2 silences normal developmental pathways leading to epigenetic transformation independent from canonical growth factor pathway activation. As such, tumors feature a transcriptional program distinct from KRAS- and EGFR-mutant mouse lung cancers, but shared with human lung adenocarcinomas exhibiting high EZH2 expression. To target EZH2-dependent cancers, we developed a novel and potent EZH2 inhibitor JQEZ5 that promoted the regression of EZH2-driven tumors in vivo, confirming oncogenic addiction to EZH2 in established tumors and providing the rationale for epigenetic therapy in a subset of lung cancer