240 research outputs found

    The Effects of Continuous Improvement Practices Using State Value-Added Data for Reading Educator Program Enhancement

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    Louisiana’s value-added evaluation of teacher preparation programs has provided a salient impetus for program improvement; however, due to the nature of the assessment, teacher preparation programs need to use additional sources of data to identify actionable responses to the value-added results. This paper describes one teacher preparation program’s approach to continuous program improvement in reading education and describes some of the limitations and benefits of value-added assessment results for that purpose

    Use of Near-Infrared Spectroscopic Analysis of Second Trimester Amniotic Fluid to Assess Preterm Births

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    This pilot study investigated the possibility that metabolomic differences exist in second trimester of women delivering at term (β‰₯37 weeks, n = 216) and preterm (≀35 weeks, n = 11). For this retrospective study, biobanked AF samples underwent near-infrared (NIR) spectral analysis using wavelengths from 700 to 1050 nm. Spectral data was compressed then optimized by multilinear regression to create a calibration model. The resultant model was able to classify term and preterm births based on differing AF metabolomic profiles with a sensitivity and specificity of 100%. When groups were classified using a prematurity index (PI), there was a statistical difference (P < 0.001) between the predicted preterm group (PI 0.77 Β± 0.08) and the term group (PI 1.00 Β± 0.02). In conclusion, the 2nd trimester AF samples showed distinct differences in metabolomic profiles between patients delivering preterm as compared to those at term in functional groups related to proteins, carbohydrates, fats, polyols, and water

    Pathways to clinical CLARITY: volumetric analysis of irregular, soft, and heterogeneous tissues in development and disease

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    AbstractThree-dimensional tissue-structural relationships are not well captured by typical thin-section histology, posing challenges for the study of tissue physiology and pathology. Moreover, while recent progress has been made with intact methods for clearing, labeling, and imaging whole organs such as the mature brain, these approaches are generally unsuitable for soft, irregular, and heterogeneous tissues that account for the vast majority of clinical samples and biopsies. Here we develop a biphasic hydrogel methodology, which along with automated analysis, provides for high-throughput quantitative volumetric interrogation of spatially-irregular and friable tissue structures. We validate and apply this approach in the examination of a variety of developing and diseased tissues, with specific focus on the dynamics of normal and pathological pancreatic innervation and development, including in clinical samples. Quantitative advantages of the intact-tissue approach were demonstrated compared to conventional thin-section histology, pointing to broad applications in both research and clinical settings.</jats:p

    Predictors of rapid aortic root dilation and referral for aortic surgery in Marfan syndrome

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    Few data exist regarding predictors of rapid aortic root dilation and referral for aortic surgery in Marfan syndrome (MFS). To identify independent predictors of the rate of aortic root (AoR) dilation and referral for aortic surgery, we investigated the data from the Pediatric Heart Network randomized trial of atenolol versus losartan in young patients with MFS. Data were analyzed from the echocardiograms at 0, 12, 24, and 36months read in the core laboratory of 608 trial subjects, aged 6months to 25 years, who met original Ghent criteria and had an AoR z-score (AoRz)>3. Repeated measures linear and logistic regressions were used to determine multivariable predictors of AoR dilation. Receiver operator characteristic curves were used to determine cut-points in AoR dilation predicting referral for aortic surgery. Multivariable analysis showed rapid AoR dilation as defined by change in AoRz/year>90th percentile was associated with older age, higher sinotubular junction z-score, and atenolol use (R-2=0.01) or by change in AoR diameter (AoRd)/year>90th percentile with higher sinotubular junction z-score and non-white race (R-2=0.02). Referral for aortic root surgery was associated with higher AoRd, higher ascending aorta z-score, and higher sinotubular junction diameter:ascending aorta diameter ratio (R-2=0.17). Change in AoRz of 0.72 SD units/year had 42% sensitivity and 92% specificity and change in AoRd of 0.34cm/year had 38% sensitivity and 95% specificity for predicting referral for aortic surgery. In this cohort of young patients with MFS, no new robust predictors of rapid AoR dilation or referral for aortic root surgery were identified. Further investigation may determine whether generalized proximal aortic dilation and effacement of the sinotubular junction will allow for better risk stratification. Rate of AoR dilation cut-points had high specificity, but low sensitivity for predicting referral for aortic surgery, limiting their clinical use. Clinical Trial Number ClinicalTrials.gov number, NCT00429364

    Hospital Costs Related to Early Extubation after Infant Cardiac Surgery

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    Background The Pediatric Heart Network Collaborative Learning Study (PHN CLS) increased early extubation rates after infant Tetralogy of Fallot (TOF) and coarctation (CoA) repair across participating sites by implementing a clinical practice guideline (CPG). The impact of the CPG on hospital costs has not been studied. Methods PHN CLS clinical data were linked to cost data from Children’s Hospital Association by matching on indirect identifiers. Hospital costs were evaluated across active and control sites in the pre- and post-CPG periods using generalized linear mixed effects models. A difference-in-difference approach was used to assess whether changes in cost observed in active sites were beyond secular trends in control sites. Results Data were successfully linked on 410/428 (96%) of eligible patients from 4 active and 4 control sites. Mean adjusted cost/case for TOF repair was significantly reduced in the post-CPG period at active sites (42,833vs.42,833 vs. 56,304, p<0.01) and unchanged at control sites (47,007vs.47,007 vs. 46,476, p=0.91), with an overall cost reduction of 27% in active vs. control sites (p=0.03). Specific categories of cost reduced in the TOF cohort included clinical (-66%, p<0.01), pharmacy (-46%, p=0.04), lab (-44%, p<0.01), and imaging (-32%, p<0.01). There was no change in costs for CoA repair at active or control sites. Conclusions The early extubation CPG was associated with a reduction in hospital costs for infants undergoing repair of TOF, but not CoA repair. This CPG represents an opportunity to both optimize clinical outcome and reduce costs for certain infant cardiac surgeries

    Whole cell screen for inhibitors of pH homeostasis in Mycobacterium tuberculosis

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    Bacterial pathogens like Mycobacterium tuberculosis (Mtb) encounter acidic microenvironments in the host and must maintain their acid-base homeostasis to survive. A genetic screen identified two Mtb strains that cannot control intrabacterial pH (pHIB) in an acidic environment; infection with either strain led to severe attenuation in mice. To search for additional proteins that Mtb requires to survive at low pH, we introduced a whole-cell screen for compounds that disrupt pHIB, along with counter-screens that identify ionophores and membrane perturbors. Application of these methods to a natural product library identified four compounds of interest, one of which may inhibit novel pathway(s). This approach yields compounds that may lead to the identification of pathways that allow Mtb to survive in acidic environments, a setting in which Mtb is resistant to most of the drugs currently used to treat tuberculosis

    Prokayrotic Ubiquitin-Like Protein (Pup) Proteome of Mycobacterium tuberculosis

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    Prokaryotic ubiquitin-like protein (Pup) in Mycobacterium tuberculosis (Mtb) is the first known post-translational small protein modifier in prokaryotes, and targets several proteins for degradation by a bacterial proteasome in a manner akin to ubiquitin (Ub) mediated proteolysis in eukaryotes. To determine the extent of pupylation in Mtb, we used tandem affinity purification to identify its β€œpupylome”. Mass spectrometry identified 55 out of 604 purified proteins with confirmed pupylation sites. Forty-four proteins, including those with and without identified pupylation sites, were tested as substrates of proteolysis in Mtb. Under steady state conditions, the majority of the test proteins did not accumulate in degradation mutants, suggesting not all targets of pupylation are necessarily substrates of the proteasome under steady state conditions. Four proteins implicated in Mtb pathogenesis, Icl (isocitrate lyase), Ino1 (inositol-1-phosphate synthase), MtrA (Mtb response regulator A) and PhoP (phosphate response regulator P), showed altered levels in degradation defective Mtb. Icl, Ino1 and MtrA accumulated in Mtb degradation mutants, suggesting these proteins are targeted to the proteasome. Unexpectedly, PhoP was present in wild type Mtb but undetectable in the degradation mutants. Taken together, these data demonstrate that pupylation regulates numerous proteins in Mtb and may not always lead to degradation

    Six-Year Neurodevelopmental Outcomes for Children With Single-Ventricle Physiology

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    OBJECTIVES: To determine if neurodevelopmental deficits in children with single-ventricle physiology change with age and early developmental scores predict 6-year outcomes. METHODS: In the Single Ventricle Reconstruction Trial, Bayley Scales of Infant Development, Second Edition, were administered at 14 months of age, and parents completed the Behavior Assessment System for Children, Second Edition (BASC-2) annually from the ages of 2 to 6 years. Scores were classified as average, at risk, or impaired. We calculated sensitivities, specificities, and positive and negative predictive values of earlier tests on 6-year outcomes. RESULTS: Of 291 eligible participants, 244 (84%) completed the BASC-2 at 6 years; more Single Ventricle Reconstruction participants than expected on the basis of normative data scored at risk or impaired on the BASC-2 Adaptive Skills Index at that evaluation (28.7% vs 15.9%; P < .001). Children with Adaptive Skills Composite scores <2 SD below the mean at the age of 6 were more likely to have had delayed development at 14 months, particularly on the Psychomotor Development Index (sensitivity of 79%). However, the positive predictive value of the 14-month Mental Development Index and Psychomotor Development Index for 6-year BASC-2 Adaptive Scores was low (44% and 36%, respectively). Adaptive Skills Composite score impairments at the age of 6 were poorly predicted by using earlier BASC-2 assessments, with low sensitivities at the ages of 3 (37%), 4 (48%), and 5 years (55%). CONCLUSIONS: Many children with hypoplastic left heart syndrome who have low adaptive skills at the age of 6 years will not be identified by screening at earlier ages. With our findings, we highlight the importance of serial evaluations for children with critical congenital heart disease throughout development
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