245 research outputs found

    Documenting heritage language experience using questionnaires

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    Introduction: There exists a great degree of variability in the documentation of multilingual experience across different instruments. The present paper contributes to the “methods turn” and individual differences focus in (heritage) bilingualism by proposing a comprehensive online questionnaire building on existing questionnaires and the experience of using them to document heritage bilingualism: the Heritage Language Experience (HeLEx) online questionnaire. HeLEx is validated against and contrasted to an extended version of the Language and Social Background Questionnaire designed for heritage speakers (HSs), LSBQ-H. Methods: We compare data elicited with both questionnaires in turn from a group of Turkish HSs (n = 174, mean age=32). Our validation focuses on traditional language background variables, including language exposure and use, language proficiency, language dominance, as well as a more novel measure of language entropy. The analyses are based on a subset of key questions from each questionnaire that capture language experience for up to five languages, four modalities, and five social contexts. In a subsequent set of analyses, we explore the impact of different types of response scales, response mechanisms, and manners of variable derivation on the informativity of the data they can provide, in terms of the scope, granularity and distributional properties of the derived measures. Results and Discussion: Our results show that both HeLEx and LSBQ-H are successful at detecting the important distributional patterns in the data and reveal a number of advantages of HeLEx. In the discussion, we consider the impact of methodological choices regarding question phrasing, visual format, response options, and response mechanisms. We emphasize that these choices are not trivial and can affect the derived measures and subsequent analyses on the impact of individual differences on language acquisition and processing

    How to quantify bilingual experience? Findings from a Delphi consensus survey

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    While most investigations of bilingualism document participants’ language background, there is an absence of consensus on how to quantify bilingualism. The high number of different language background questionnaires used by researchers and practitioners jeopardises data comparability and cross-pollination between research and practice. Using the Delphi consensus survey method, we asked 132 panellists (researchers, speech and language therapists, teachers) from 29 countries to rate 124 statements on a 5-point agreement scale. Consensus was pre-defined as 75% agreement threshold. After two survey rounds, 79% of statements reached consensus. The need for common measures to quantify bilingualism was acknowledged by 96% of respondents. Agreement was reached to document: language exposure and use, language difficulties, proficiency (when it cannot be assessed directly), education and literacy, input quality, language mixing practices, and attitudes (towards languages and language mixing). We discuss the implications of these findings for the creation of a new tool to quantify bilingual experience

    A Case Study of Tire Crumb Use on Playgrounds: Risk Analysis and Communication When Major Clinical Knowledge Gaps Exist

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    Physicians and public health professionals working with the U.S. Environmental Protection Agency’s Region 8 Pediatric Environmental Health Specialty Unit (PEHSU) received several telephone calls requesting information regarding the safety of recycled tire crumb as a playground surface constituent placed below children’s play structures. There were no reported symptoms or adverse health effects in exposed children. The literature available on the safety and risk of exposure to crumb rubber constituents was limited and revealed no information quantifying exposures associated with product use. Callers were informed by the PEHSU that no evidence existed suggesting harm from intended use of the product, but gaps in knowledge about the product were identified and communicated. Here the case of crumb rubber on playgrounds is used as a model to present an approach to similar environmental medicine questions. From defining the question, to surveying traditional and nontraditional resources for information, synthesis of findings, and risk communication, the case provides a model to approach similar questions

    BRAF V600E mutations in urine and plasma cell-free DNA from patients with Erdheim-Chester disease.

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    Erdheim-Chester disease (ECD) is a rare histiocytosis with a high prevalence of BRAF V600E mutation (>50% of patients). Patients with BRAF-mutant ECD can respond to BRAF inhibitors. Unfortunately, the lack of adequate archival tissue often precludes BRAF testing. We hypothesized that cell-free DNA (cfDNA) from plasma or urine can offer an alternative source of biologic material for testing. We tested for BRAF V600E mutation in cfDNA from the plasma and urine of 6 ECD patients. In patients with available archival tissue, the result of BRAF mutation analysis was concordant with plasma and urine cfDNA results in all 3 patients (100% agreement, kappa 1.00). In all 6 patients, BRAF mutation analysis of plasma and urine cfDNA was concordant in 5 of 6 patients (83% agreement, kappa 0.67). Testing for BRAF V600E mutation in plasma and urine cfDNA should be further investigated as an alternative to archival tissue mutation analysis

    Pre-existing immunity to SARS-CoV-2 before the COVID-19 pandemic era in Cameroon: A comparative analysis according to HIV-status

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    BackgroundThe lower burden of COVID-19 in tropical settings may be due to preexisting cross-immunity, which might vary according to geographical locations and potential exposure to other pathogens. We sought to assess the overall prevalence of SARS-CoV-2 antibodies and determine SARS-CoV-2 seropositivity according to HIV-status before the COVID-19 pandemic era. MethodsA cross-sectional and comparative study was conducted at the Chantal BIYA International Reference Centre (CIRCB) on 288 stored plasma samples (163 HIV-positive versus 125 HIV-negative); all collected in 2017-2018, before the COVID-19 pandemic era. Abbott Panbio (TM) COVID-19 IgG/IgM assay was used for detecting SARS-CoV-2 immunoglobulin G (IgG) and M (IgM). Among people living with HIV (PLHIV), HIV-1 viral load and TCD4 cell count (LTCD4) were measured using Abbott Real Time PCR and BD FACSCalibur respectively. Statistical analyses were performed, with pResultsThe median [IQR] age was 25 [15-38] years. Overall seropositivity to SARS-CoV-2 antibodies was 13.5% (39/288) of which 7.3% (21) was IgG, 7.3% (21) IgM and 1.0% (3) IgG/IgM. According to HIV-status in the study population, SARS-CoV-2 seropositivity was 11.0% (18/163) among HIV-positive versus 16.8% (21/125) among HIV-negative respectively, p=0.21. Specifically, IgG was 6.1% (10/163) versus 8.8% (11/125), p=0.26; IgM was 5.5% (9/163) versus 9.6%, (12/125), p=0.13 and IgG/IgM was 0.6% (1/163) versus 1.6% (2/125) respectively. Among PLHIV, SARS-CoV-2 seropositivity according to CD4 count was 9.2% (>= 500 cells/mu L) versus 1.8% (200-499 cells/mu L), (OR=3.5; p=0.04) and 0.6% (<200 cells/mu L), (OR=17.7; p<0.01). According to viral load, SARS-CoV-2 seropositivity was 6.7% (>= 40 copies/mL) versus 4.9% (<40 copies/mL), (OR= 3.8; p<0.01). ConclusionBefore COVID-19 in Cameroon, cross-reactive antibodies to SARS-CoV-2 were in circulation, indicating COVID-19 preexisting immunity. This preexisting immunity may contribute in attenuating disease severity in tropical settings like Cameroon. Of relevance, COVID-19 preexisting immunity is lower with HIV-infection, specifically with viral replication and poor CD4-cell count. As poor CD4-count leads to lower cross-reactive antibodies (regardless of viral load), people living with HIV appear more vulnerable to COVID-19 and should be prioritized for vaccination

    Life-threatening influenza pneumonitis in a child with inherited IRF9 deficiency

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    Life-threatening pulmonary influenza can be caused by inborn errors of type I and III IFN immunity. We report a 5-yr-old child with severe pulmonary influenza at 2 yr. She is homozygous for a loss-of-function IRF9 allele. Her cells activate gamma-activated factor (GAF) STAT1 homodimers but not IFN-stimulated gene factor 3 (ISGF3) trimers (STAT1/STAT2/IRF9) in response to IFN-α2b. The transcriptome induced by IFN-α2b in the patient's cells is much narrower than that of control cells; however, induction of a subset of IFN-stimulated gene transcripts remains detectable. In vitro, the patient's cells do not control three respiratory viruses, influenza A virus (IAV), parainfluenza virus (PIV), and respiratory syncytial virus (RSV). These phenotypes are rescued by wild-type IRF9, whereas silencing IRF9 expression in control cells increases viral replication. However, the child has controlled various common viruses in vivo, including respiratory viruses other than IAV. Our findings show that human IRF9- and ISGF3-dependent type I and III IFN responsive pathways are essential for controlling IAV

    Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

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    BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

    STAT3/LKB1 controls metastatic prostate cancer by regulating mTORC1/CREB pathway

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    Prostate cancer (PCa) is a common and fatal type of cancer in men. Metastatic PCa (mPCa) is a major factor contributing to its lethality, although the mechanisms remain poorly understood. PTEN is one of the most frequently deleted genes in mPCa. Here we show a frequent genomic co-deletion of PTEN and STAT3 in liquid biopsies of patients with mPCa. Loss of Stat3 in a Pten-null mouse prostate model leads to a reduction of LKB1/pAMPK with simultaneous activation of mTOR/CREB, resulting in metastatic disease. However, constitutive activation of Stat3 led to high LKB1/pAMPK levels and suppressed mTORC1/CREB pathway, preventing mPCa development. Metformin, one of the most widely prescribed therapeutics against type 2 diabetes, inhibits mTORC1 in liver and requires LKB1 to mediate glucose homeostasis. We find that metformin treatment of STAT3/AR-expressing PCa xenografts resulted in significantly reduced tumor growth accompanied by diminished mTORC1/CREB, AR and PSA levels. PCa xenografts with deletion of STAT3/AR nearly completely abrogated mTORC1/CREB inhibition mediated by metformin. Moreover, metformin treatment of PCa patients with high Gleason grade and type 2 diabetes resulted in undetectable mTORC1 levels and upregulated STAT3 expression. Furthermore, PCa patients with high CREB expression have worse clinical outcomes and a significantly increased risk of PCa relapse and metastatic recurrence. In summary, we have shown that STAT3 controls mPCa via LKB1/pAMPK/mTORC1/CREB signaling, which we have identified as a promising novel downstream target for the treatment of lethal mPCa

    The Complete Genome Sequence of Thermoproteus tenax: A Physiologically Versatile Member of the Crenarchaeota

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    Here, we report on the complete genome sequence of the hyperthermophilic Crenarchaeum Thermoproteus tenax (strain Kra 1, DSM 2078(T)) a type strain of the crenarchaeotal order Thermoproteales. Its circular 1.84-megabase genome harbors no extrachromosomal elements and 2,051 open reading frames are identified, covering 90.6% of the complete sequence, which represents a high coding density. Derived from the gene content, T. tenax is a representative member of the Crenarchaeota. The organism is strictly anaerobic and sulfur-dependent with optimal growth at 86 degrees C and pH 5.6. One particular feature is the great metabolic versatility, which is not accompanied by a distinct increase of genome size or information density as compared to other Crenarchaeota. T. tenax is able to grow chemolithoautotrophically (CO2/H-2) as well as chemoorganoheterotrophically in presence of various organic substrates. All pathways for synthesizing the 20 proteinogenic amino acids are present. In addition, two presumably complete gene sets for NADH:quinone oxidoreductase (complex I) were identified in the genome and there is evidence that either NADH or reduced ferredoxin might serve as electron donor. Beside the typical archaeal A(0)A(1)-ATP synthase, a membrane-bound pyrophosphatase is found, which might contribute to energy conservation. Surprisingly, all genes required for dissimilatory sulfate reduction are present, which is confirmed by growth experiments. Mentionable is furthermore, the presence of two proteins (ParA family ATPase, actin-like protein) that might be involved in cell division in Thermoproteales, where the ESCRT system is absent, and of genes involved in genetic competence (DprA, ComF) that is so far unique within Archaea

    Creating a space for young women's voices: Using participatory 'video drama' in Uganda

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    This article draws upon research that explored the experiences of young women in relation to sexual health in Uganda with a view to enhancing gender-sensitive strategies. We have coined the phrase ‘participatory video drama’ to describe the exploratory methodology that the young women participants in our research used to present stories about their lives. The aim of this article is to suggest that ‘participatory video’ (PV) and ‘participatory video drama’ (PVD) are innovative methodological tools to utilise when working with participants who experience voicelessness in their everyday lives. We contribute to an emerging body of work around this methodology by suggesting that the process of PV provides a novel and engaging platform for participants to express their experiences. PVD further creates spaces for the performative exploration of embedded power relations and is therefore informative and has the potential to be transformatory and empowering
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