Beyond phonotactic frequency: Presentation frequency effects word productions in specific language impairment

Phonotactic frequency effects on word production are thought to reflect accumulated experience with a language. Here we demonstrate that frequency effects can also be obtained through short-term manipulations of the input to children. We presented children with nonwords in an experiment that systematically manipulated English phonotactic frequency and the frequency of presentation within the experiment. Both of these manipulations affected the accuracy and time-to-response for nonword production both for typically developing and children with specific language impairment. Children with SLI were less accurate in their productions overall, but still exhibited an effect of the short-term frequency manipulation. Children with SLI differed significantly from their typical peers in terms of time-to-response only when both English and Experimental frequency were low. The results indicate that simple manipulations of the input can affect children's representation of word forms, and this can facilitate word production without the need for long term exposure or articulatory practice.Learning outcomes: The reader will learn that sound frequency affects the production of new words. This includes not only the frequency with which sound sequences are represented in the speaker's native language, but the frequency with which they are heard within a single session.     

Children with specific language impairment show rapid,implicit learning of stress assignment rules

An implicit learning paradigm was used to assess children's sensitivity to syllable stress information in an artificial language. Study 1 demonstrated that preschool children, with and without specific language impairment (SLI), can generalize patterns of stress heard during a brief period of familiarization, and can also abstract underlying ordered rules by which stress patterns were assigned to syllables. In Study 2, the salience of stressed elements was acoustically enhanced. Counter to expectations, there was no evidence of learning with this manipulation for either the typically developing children or children with SLI. The results suggest that children with SLI and their typically developing peers are sensitive to syllable stress cues to language structure. However, attempts to draw attention to these patterns by making them more salient may prompt children to use alternate learning strategies that do not lead to an implicit understanding of how stress contributes to the structure of language.Learning outcomes: The reader will be able to understand: (1) that children with SLI can learn and generalize the rules for assigning word-level stress patterns within minutes of hearing examples, but (2) strategies to enhance learning may actually have the opposite effect for these children.     

The relationship between quality of life and compliance to a brace protocol in adolescents with idiopathic scoliosis: a comparative study

Background  

Corrective bracing for adolescent idiopathic scoliosis (AIS) has favourable outcomes when patients are compliant. However, bracing may be a stressful and traumatic experience and compliance with a bracing protocol is likely to be dependent upon patients' physical, emotional and social wellbeing. The Brace Questionnaire (BrQ), a recently-developed, condition-specific tool to measure quality of life (QOL) has enabled clinicians to study relationships between QOL and compliance.     

Chk1 inhibition and Wee1 inhibition combine synergistically to impede cellular proliferation

Inhibition of the checkpoint kinase Chk1, both as a monotherapy and in combination with DNA damaging cytotoxics, is a promising therapeutic approach for the treatment of a wide array of human cancers. However, much remains to be elucidated in regard to the patient populations that will respond best to a Chk1 inhibitor and the optimal therapeutics to combine with a Chk1 inhibitor. In an effort to discover sensitizing mutations and novel combination strategies for Chk1 inhibition, an siRNA screen was performed in combination with the selective Chk1 inhibitor AR458323. This screen employed a custom made library of siRNAs targeting 195 genes, most of which are involved in cell-cycle control or DNA damage repair. One of the most prominent and consistent hits across runs of the screen performed in three different cancer cell lines was Wee1 kinase. MK-1775 is a small molecule inhibitor of Wee1 that is currently in early stage clinical trials. In confirmation of the results obtained from the siRNA screen, AR458323 and MK-1775 synergistically inhibited proliferation in multiple cancer cell types. This antiproliferative effect correlated with a synergistic induction of apoptosis. In cellular mechanistic studies, the combination of the two molecules resulted in dramatic decreases in inhibitory phosphorylation of cyclin-dependent kinases, an increase in DNA damage, alterations in cell-cycle profile, and collapse of DNA synthesis. In conclusion, the clinical combination of a Chk1 inhibitor and a Wee1 inhibitor holds promise as an effective treatment strategy for cancer.     

Relationship between scaffold channel diameter and number of regenerating axons in the transected rat spinal cord

Regeneration of endogenous axons through a Schwann cell (SC)-seeded scaffold implant has been demonstrated in the transected rat spinal cord. The formation of a cellular lining in the scaffold channel may limit the degree of axonal regeneration. Spinal cords of adult rats were transected and implanted with the SC-loaded polylactic co-glycollic acid (PLGA) scaffold implants containing seven parallel-aligned channels, either 450 μm (n = 19) or 660 μm in diameter (n = 14). Animals were sacrificed after 1, 2 and 3 months. Immunohistochemistry for neurofilament expression was performed. The cross-sectional area of fibrous tissue and regenerative core was calculated. We found that the 450 μm scaffolds had significantly greater axon fibers per channel at the 1 month (186 ± 37) and 3 month (78 ± 11) endpoints than the 660 μm scaffolds (90 ± 19 and 40 ± 6, respectively) (p = 0.0164 and 0.0149, respectively). The difference in the area of fibrous rim between the 450 and 660 μm channels was most pronounced at the 1 month endpoint, at 28,046 ± 6551 and 58,633 ± 7063 μm², respectively (p = 0.0105). Our study suggests that fabricating scaffolds with smaller diameter channels promotes greater regeneration over larger diameter channels. Axonal regeneration was reduced in the larger channels due to the generation of a large fibrous rim. Optimization of this scaffold environment establishes a platform for future studies of the effects of cell types, trophic factors or pharmacological agents on the regenerative capacity of the injured spinal cord.     

Correlation of radiographic cardiothoracic ratio with cardiac function in patients with acute congestive heart failure

Objective: Plain film radiographs are routinely used as a part of the emergency department evaluation of patients with acute congestive heart failure. Determination of the cardiothoracic ratio (CT ratio) may provide insight into the severity and mechanism of the cardiac dysfunction. This study was designed to correlate the determined CT ratio with measures of systolic and diastolic function in patients with decompensated congestive heart failure (CHF). Methods: The CT ratio was retrospectively calculated from the routine upright anteroposterior plain film radiographs obtained during the evaluation of patients with acute CHF. Likewise, values for the diastolic time intervals such as isovolumic relaxation times and filling times (measures of diastolic dysfunction, IVRT, FT) and the Heather Index (a measure of systolic contractility, HI) were obtained from the tracings obtained by impedance cardiography (IC). These functional measures were then independently correlated with the CT ratio by multiple regression analysis. The degree of left ventricular hypertrophy (LVH) as determined by EKG voltage was also correlated to cardiac function measures for comparison. Results: In 45 patients there was no significant correlation (P < 0.05) of the measured IVRT and FT with the corresponding CT ratio. The HI was also significantly inversely correlated with the CT ratio (r = –0.36, P < 0.05). By comparison, the degree of LVH was not significantly related to the measures of systolic function but was highly correlated to the IVRT. Conclusion: CT ratios determined from plain film radiographs appear to correlate well with measures of cardiac systolic function and may be useful in determining the severity and mechanism of CHF in the acute setting.     

Methodology for measuring diversity in human populations

A population is considered diverse if it contains individuals with a wide variety of demographic and cultural characteristics or attributes. However, it is often difficult to compare the relative diversity of two groups. It is even more difficult to specifically measure or quantify the diversity of any single group. In this paper a three step process for measuring and quantifying diversity in a human populations is described. The measurement methodologies illustrated in an example using this process are based upon fractionalization techniques and mathematical information theory.     

Effect of GDF‐7 deficiency on tail tendon phenotype in mice

The subfamily of growth/differentiation factors (GDFs) known as GDFs 5, 6, and 7 appears to be involved in tendon maintenance and repair, although the precise nature of this role has yet to be elucidated. The aim of the present study was to examine the role of GDF‐7 in tendon maintenance by studying tail tendon fascicle gene expression, composition, and material property strain rate dependency in 16‐week‐old male and female GDF‐7 deficient mice. GDF‐7 deficiency did not affect the biochemical composition of tail tendon fascicles, nor did it significantly affect the tensile material properties obtained at either slow (5%/s) or fast (50%/s) strain rates. Further, no difference was found between genotypes in the strain rate sensitivity of any tensile material property. Consistent with the compositional analyses, QRT‐PCR data did not reveal any differences of twofold or greater in the gene expression levels of collagens I, III, V, nor in the proteoglycans decorin, fibromodulin, lumican, biglycan, versican, or aggrecan. Gdf5 expression was upregulated twofold in GDF‐7 deficient tail tendons, and Bmp7 expression was downregulated twofold. No notable differences in expression levels for Bmp1‐6 or Gdf6 were detected. GDF‐5 protein levels were 50% higher in GDF‐7 deficient tail tendon compared to wild type tail tendon. The results of this study support the intriguing possibility that compensation by Gdf‐5 may be at least in part responsible for the absence of a strong phenotype in GDF‐7 deficient mice. © 2008 Orthopaedic Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:834–839, 2008     

Virus encoding an encephalitogenic peptide protects mice from experimental allergic encephalomyelitis

The association of vital infections with autoimmune central nervous system (CNS) diseases such as post-infectious encephalomyelitis and possibly multiple sclerosis (MS) prompted the investigation to understand how virus infection could modulate autoimmune responses. Recombinant vaccinia viruses encoding an encephalitogenic portion of myelin basic protein (MBP) were evaluated in an animal model for human demyelinating disease, experimental allergic encephalomyelitis (EAE). We have determined that mice vaccinated with recombinant viruses encoding an encephalitogenic region of MBP were protected from EAE. In vivo depletion of CD8⁺ T cells did not abrogate this protection, suggesting lack of regulation by this cell type. These studies demonstrate that virus infection may be a means to modulate immune responsiveness to CNS disease.