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PURPOSE: This study investigated the longitudinal, cross-linguistic developmental relationships of phonological awareness (PA), letter identification (letter ID), and morphological awareness (MA) in 71 heritage Spanish-English dual language learners (DLLs) in kindergarten and second grade. METHOD: Multiple linear regression was used to test if kindergarten Spanish and English PA (sound elision and sound matching) and letter ID significantly predicted later English MA (oral derived word stress judgment, oral derivational morpheme blending, written derived word decomposition, and morphologically complex word spelling) performance in second grade. RESULTS: Cross-linguistically, the PA skill of sound matching in kindergarten was the most reliable predictor of MA in second grade for Spanish-English DLLs. Spanish PA explained the majority of variation in oral MA skills in English. English PA was only uniquely predictive of written MA skills in English. CONCLUSIONS: Both the cognitive operation of sound sequence manipulation in PA (elision or matching) and the modality of morpheme representation in MA (oral or written) appear to mediate the transfer of metalinguistic knowledge in Spanish-English DLL development in early elementary school. Results are discussed within the context of classroom practices.

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BACKGROUND: Many GPs are challenged to deliver safe and effective care for patients who use alcohol and other drugs (AOD). The Royal Australian College of General Practitioners (RACGP) developed the AOD GP Education Programme to support Australian GPs and optimise AOD care in the community. How the programme impacted GP participants is not yet fully understood. AIM: To explore the views and experiences of GP participants who completed the AOD GP Education Programme, and AOD experts who were involved in the programme as a presenter or mentor. DESIGN & SETTING: Situated in the constructivist paradigm, this qualitive descriptive study engaged GPs across Australia. METHOD: This study employed semi-structured, online, focus groups interviews. Data were analysed thematically. RESULTS: Five focus groups were held with a total of 35 GP participants. Five themes developed, which illustrated that the study participants viewed the programme design as comprehensive and flexible. It has also been shown that participants' individual learning needs were addressed. Impacts of the programme on clinical practice included the following: confidence to care for patients who use AOD; confidence to collaborate with colleagues in delivery of AOD care; confidence to develop AOD professional networks in their community setting; and confidence to manage complex AOD presentations. CONCLUSION: Participants described the AOD programme as a high quality and positive educational experience. The prioritisation of core treatment skills (whole-person care and structured approaches to behavioural change) was a feature of the professional development programme. The AOD programme design is a practical model to implement for future AOD GP education and continuing professional development.

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Yoga is a multidimensional and heterogeneous mind-body practice led by a therapist or teacher (e.g., yoga instructor). Although they constitute an integral part of delivery, content, and curriculum, factors that influence yoga instructors' choices have yet to be explored. Using a mixed methods sequential design for development of an instrument that identifies measurable epistemic (YIBS-E) and pedagogic (YIBS-P) beliefs, the Yoga Instructor Beliefs Scale (YIBS) reports validity evidence from four distinct phases. Phase I presents qualitative findings from literature-informed semistructured interviews to give a comprehensive construct model of yoga instructor beliefs from diverse styles/ schools/lineages of yoga (nine content-specific clusters). In Phase II, focus group panels of experts evaluated construct novelty and importance of themes, resulting in a pool of potential questionnaire items. Phase III employed cognitive interviews to assess the perceived meaning and clarity of using the preliminary YIBS items. Phase IV included exploratory factor analysis and correlational analyses using 204 yoga instructor responses, suggesting a 44-item instrument with distinct epistemic (Experiential, Energetic, Systems-Based, Affectual, Mindful, and Physical) and pedagogic (Curricular Integration, Student Awareness, Accessibility, and Differentiated Instruction) factors (YIBS- E α = 0.90, YIBS-P α = 0.85). Measurable belief constructs can inform research on individual yoga instructor differences that may influence curriculum content choices and delivery. The purpose of this instrument is to enable research linking instructor beliefs to the presence of various components of a yoga program and to contextualize defining qualities of yoga programs. Long-term use of this instrument should enable in-depth analyses such as mediation or moderation of yoga instructor beliefs on intervention components/content or outcomes.

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This cross-sectional study applied the intergroup contact theory in the context of transgender prejudice and examined the relationships between quality and quantity of contact and explicit and implicit anti-transgender prejudice. Additionally, the study assessed the possible mediating role of intergroup anxiety in the relationship between intergroup contact and anti-transgender prejudice. Structural equation modeling was used to examine the proposed relationships, controlling for gender, religiosity, and political conservatism. Data were collected from an online sample of 354 participants (males: n = 168; females: n = 186). As hypothesized, greater quantity of contact was uniquely related to less implicit anti-transgender prejudice, whereas greater quality of contact was uniquely related to less explicit and implicit anti-transgender prejudice. Intergroup anxiety mediated the relationships between quality of contact and implicit and explicit anti-transgender prejudice but did not mediate the relationship between quantity of contact and implicit anti-transgender prejudice.

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BACKGROUND: Assessment of pure polysaccharide response to the 23-valent pneumococcal polysaccharide vaccine (PPV23) can be biased by previous exposure to the conjugate vaccine (PCV). We applied pre-analytical modification to the existing ELISA by pre-incubating serum with PCV. METHODS: PCV-adsorbed and non-adsorbed sera were prepared before measuring the concentration of anti-pneumococcal capsular polysaccharide (PCP) IgG antibodies by the whole pneumococcal ELISA. Paired pre and post-pneumococcal vaccination sera from 73 subjects were analyzed and the baseline anti-PCP IgG for each sample was subtracted from the post-vaccination value to measure vaccine responses. Absolute change in titers and fold changes were then compared between both methods. RESULTS: In the PCV-vaccinated group (n = 28), pre-adsorption with PCV significantly reduced the vaccine responses compared to non-adsorbed sera [median increase in anti-PCP titers: 27.55 mg/l and 45.98 mg/l, respectively]. In addition, the median fold change dropped significantly from 3.026 to 2.313. In PPV23-vaccinated immunocompetent subjects (n = 28) there was a significant difference in anti-PCP responses with PCV adsorption [median values: 73.71 mg/l without and 51.04 mg/l with adsorption]. All the antibody deficiency patients (n = 17) displayed poor PPV23 responses. Although PPV23 responsiveness was not statistically different between both methods, we have observed a trend for lower anti-PCP IgG titers in PCV-adsorbed sera compared to non-adsorbed ones. Serotype-specific IgG analysis using a multiplexed bead-based immunoassay performed on 10 paired samples confirmed that the adsorption observed is specific to PCV serotypes. CONCLUSION: Pre-analytical modification to the conventional ELISA by removing the PCV-specific serotypes may differentiate true polysaccharide response from recall response induced by previous PCV vaccination.

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Background: The assessment of specific polysaccharide antibody production plays a pivotal role in the diagnosis of humoral primary immunodeficiencies (PID). The response to 23-valent pneumococcal vaccine (PPV) remains the gold standard for the diagnosis of polysaccharide antibodies. However, in Spain, the interpretation of pure polysaccharide 23-valent immunization is hampered by the high endemicity of pneumococcal disease and the generalization of the 13-valent adjuvant pneumococcal vaccination. Specific Typhim Vi vaccination (TV) immunoglobulin G IgG response to immunization is useful in adult PID, but there is no data regarding children. Objectives: To evaluate the clinical utility of TV IgG production as a diagnostic tool to determine anti-polysaccharide antibody production deficiency in children, when the response to PPV is unclear and isolated determination of serotypes is unfeasible. Methods: We conducted a single-institution prospective observational study on 61 children with recurrent infections. Baseline specific antibodies against PPV and TV were evaluated. In 28 children (46%), the response to the production of antibodies confirmed a clinical suspicion of humoral PID, and they were therefore immunized with 23-valent pneumococcal vaccine and Typhim Vi. Both specific antibody responses were measured by ELISA (The Binding Site Group Ltd, Birmingham, UK) using previously published cut-offs. Results: Seventy percent of the 61 children displayed baseline PPV IgG > 27 mg/L, whereas only 8% showed TV IgG > 28 U/mL (p < 0.0001). Twenty-one of 28 children (75%) achieved a 3-fold increase in post-vaccination TV IgG levels, whereas only 3% achieved a 4-fold increase in PPV IgG post vaccination, mainly due to high baseline PPV IgG titers. When we classified children according to their response to TV as responders or non-responders and compared this with the well-known clinical warning signs of the Jeffrey Modell Foundation. The proportions of children with history of pneumonia and the need for intravenous antibiotics were significantly higher in TV IgG non-responders than in TV IgG responders (p = 0.02 and p = 0.01, respectively). Conclusion: Response to TV can be considered an ancillary diagnostic tool to determine polysaccharide antibodies in children, particularly when isolated determination of pneumococcal serotypes is not feasible. TV provides a useful asset for clinicians in the era of conjugate PPV vaccination, with clinical relevance. Further research is warranted for validation.

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The present study evaluated the efficacy of equivalence-based instruction (EBI) as described in the PEAK-E curriculum (Dixon, 2015) for promoting the emergence of derived geometry skills in two children with high-functioning autism. The results suggested that direct training of shape name (A) to shape property (B) (i.e., A-B relations) was effective for both participants. Following A-B training, both participants demonstrated emergent relations that are consistent with symmetry (B-A), as well as emergent shape name (A) to shape picture (C) relations that are consistent with transitivity (A-C). The results expand on existing literature by demonstrating the emergence of an A-C relation when neither A nor B stimuli were ever trained to C stimuli and illustrate the efficacy of EBI for training geometry skills.

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Modulation of the cell cycle may underlie the toxicologic or pharmacologic responses of a potential therapeutic agent and contributes to decisions on its preclinical and clinical safety and efficacy. The descriptive and quantitative assessment of normal, aberrant, and degenerate mitotic figures in tissue sections is an important end point characterizing the effect of xenobiotics on the cell cycle. Historically, pathologists used manual counting and special staining visualization techniques such as immunohistochemistry for quantification of normal, aberrant, and degenerate mitotic figures. We designed an automated image analysis algorithm for measuring these mitotic figures in hematoxylin and eosin (H&E)-stained sections. Algorithm validation methods used data generated from a subcutaneous human transitional cell carcinoma xenograft model in nude rats treated with the cell cycle inhibitor Eg5. In these studies, we scanned and digitized H&E-stained xenografts and applied a complex ruleset of sequential mathematical filters and shape discriminators for classification of cell populations demonstrating normal, aberrant, or degenerate mitotic figures. The resultant classification system enabled the representations of three identifiable degrees of morphological change associated with tumor differentiation and compound effects. The numbers of mitotic figure variants and mitotic indices data generated corresponded to a manual assessment by a pathologist and supported automated algorithm verification and application for both efficacy and toxicity studies.

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PURPOSE: To estimate the rate constant for pyruvate to lactate conversion in tumours in response to a hypoxic challenge, using hyperpolarised (13)C1-pyruvate and magnetic resonance spectroscopy. METHODS AND MATERIALS: Hypoxic inspired gas was used to manipulate rat P22 fibrosarcoma oxygen tension (pO2), confirmed by luminescence decay of oxygen-sensitive probes. Hyperpolarised (13)C1-pyruvate was injected into the femoral vein of anaesthetised rats and slice-localised (13)C magnetic resonance (MR) spectra acquired. Spectral integral versus time curves for pyruvate and lactate were fitted to a precursor-product model to estimate the rate constant for tumour conversion of pyruvate to lactate (kpl). Mean arterial blood pressure (MABP) and oxygen tension (ArtpO2) were monitored. Pyruvate and lactate concentrations were measured in freeze-clamped tumours. RESULTS: MABP, ArtpO2 and tumour pO2 decreased significantly during hypoxia. kpl increased significantly (p<0.01) from 0.029±0.002s(-1) to 0.049±0.006s(-1) (mean±SEM) when animals breathing air were switched to hypoxic conditions, whereas pyruvate and lactate concentrations were minimally affected by hypoxia. Both ArtpO2 and MABP influenced the estimate of kpl, with a strong negative correlation between kpl and the product of ArtpO2 and MABP under hypoxia. CONCLUSION: The rate constant for pyruvate to lactate conversion, kpl, responds significantly to a rapid reduction in tumour oxygenation.

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The Behavioral and Emotional Screening System (BESS) is a relatively new method for identifying behavior and emotional risk (BER) in children and adolescents. Psychometric evidence regarding this instrument is important for researchers and practitioners considering the use of the BESS for identifying BER in students. Previous psychometric research specifically regarding the BESS Student Form involved the use of samples of elementary and middle school-age children. This study adds to the psychometric evidence for scores on the BESS Student Form by using samples of high school aged students to assess both the factor structure reported by Dowdy, Twyford et al. (2011) and the measurement invariance of the BESS items with regard to ethnicity, English language proficiency, and socioeconomic status. The results indicate that while the proposed 4-factor structure of the BESS Student Form is appropriate, lower than preferred reliabilities for some of the factors indicates that reporting the overall risk T score is more appropriate than reporting factor scores for risk classification purposes. Additionally, the BESS Student Form items did not exhibit measurement bias when comparing across ethnicities, language proficiency classification, or socioeconomic status (via free/reduced lunch classification).

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Previous research has investigated the influence of sample size, model misspecification, test length, ability distribution offset, and generating model on the likelihood ratio difference test in applications of item response models. This study extended that research to the evaluation of dimensionality using the multidimensional random coefficients multinomial logit model (MRCMLM). Logistic regression analysis of simulated data reveal that sample size and test length have a large effect on the capacity of the LR difference test to correctly identify unidimensionality, with shorter tests and smaller sample sizes leading to smaller Type I error rates. Higher levels of simulated misfit resulted in fewer incorrect decisions than data with no or little misfit. However, Type I error rates indicate that the likelihood ratio difference test is not suitable under any of the simulated conditions for evaluating dimensionality in applications of the MRCMLM.

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Antiangiogenic therapy based on blocking the actions of vascular endothelial growth factor-A (VEGF) can lead to "normalization" of blood vessels in both animal and human tumors. Differential expression of VEGF isoforms affects tumor vascular maturity, which could influence the normalization process and response to subsequent treatment. Fibrosarcoma cells expressing only VEGF120 or VEGF188 isoforms were implanted either subcutaneously (s.c.) or in dorsal skin-fold "window" chambers in SCID mice. VEGF120 was associated with vascular fragility and hemorrhage. Tumor-bearing mice were treated with repeat doses of SU5416, an indolinone receptor tyrosine kinase inhibitor with activity against VEGFR-2 and proven preclinical ability to induce tumor vascular normalization. SU5416 reduced vascularization in s.c. implants of both VEGF120 and VEGF188 tumors. However, in the window chamber, SU5416 treatment increased red cell velocity in VEGF120 (representing vascular normalization) but not VEGF188 tumors. SU5416 treatment had no effect on growth or necrosis levels in either tumor type but tended to counteract the increase in interstitial fluid pressure seen with growth of VEGF120 tumors. SU5416 pretreatment resulted in the normally fragile blood vessels in VEGF120-expressing tumors becoming resistant to the vascular damaging effects of the tubulin-binding vascular disrupting agent (VDA), combretastatin A4 3-O-phosphate (CA4P). Thus, vascular normalization induced by antiangiogenic treatment can reduce the efficacy of subsequent VDA treatment. Expression of VEGF120 made tumors particularly susceptible to vascular normalization by SU5416, which in turn made them resistant to CA4P. Therefore, VEGF isoform expression may be useful for predicting response to both antiangiogenic and vascular-disrupting therapy.

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