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Do emotional difficulties and peer problems hew together from childhood to adolescence? The case of children with a history of developmental language disorder (DLD)
Children and adolescents with developmental language disorder (DLD) are, overall, vulnerable to difficulties in emotional adjustment and in peer relations. However, previous research has shown that different subgroups follow different trajectories in respect of quality of peer relations. Less is known of the trajectories of emotional development. We consider here the possibility that development in these two domains is interrelated: that is, the trajectories of emotional and peer problems will proceed in parallel. We conducted longitudinal joint trajectories analyses of emotional and peer relations in a sample of young people identified as having DLD at age 7 years and seen at intervals up to 16 years. Potential influences on joint trajectory group membership were examined. Findings revealed five distinct joint trajectories. Emotional and peer difficulties do hew together from childhood to adolescence for just over half of the sample, but not all. The variables most clearly associated with group membership were pragmatic language ability, prosociality and parental mental health. This is the first study to examine joint longitudinal trajectories of emotional and peer difficulties in individuals with DLD. We demonstrate that development in individuals with DLD is heterogeneous and identify three key variables associated with personal and social adjustment from childhood to adolescence. Theoretical and clinical implications of these findings are discussed
All clinically-relevant blood components transmit prion disease following a single blood transfusion: a sheep model of vCJD
Variant CJD (vCJD) is an incurable, infectious human disease, likely arising from the consumption of BSE-contaminated meat products. Whilst the epidemic appears to be waning, there is much concern that vCJD infection may be perpetuated in humans by the transfusion of contaminated blood products. Since 2004, several cases of transfusion-associated vCJD transmission have been reported and linked to blood collected from pre-clinically affected donors. Using an animal model in which the disease manifested resembles that of humans affected with vCJD, we examined which blood components used in human medicine are likely to pose the greatest risk of transmitting vCJD via transfusion. We collected two full units of blood from BSE-infected donor animals during the pre-clinical phase of infection. Using methods employed by transfusion services we prepared red cell concentrates, plasma and platelets units (including leucoreduced equivalents). Following transfusion, we showed that all components contain sufficient levels of infectivity to cause disease following only a single transfusion and also that leucoreduction did not prevent disease transmission. These data suggest that all blood components are vectors for prion disease transmission, and highlight the importance of multiple control measures to minimise the risk of human to human transmission of vCJD by blood transfusion
The deuteron: structure and form factors
A brief review of the history of the discovery of the deuteron in provided.
The current status of both experiment and theory for the elastic electron
scattering is then presented.Comment: 80 pages, 33 figures, submited to Advances in Nuclear Physic
Parameter selection for and implementation of a web-based decision-support tool to predict extubation outcome in premature infants
BACKGROUND: Approximately 30% of intubated preterm infants with respiratory distress syndrome (RDS) will fail attempted extubation, requiring reintubation and mechanical ventilation. Although ventilator technology and monitoring of premature infants have improved over time, optimal extubation remains challenging. Furthermore, extubation decisions for premature infants require complex informational processing, techniques implicitly learned through clinical practice. Computer-aided decision-support tools would benefit inexperienced clinicians, especially during peak neonatal intensive care unit (NICU) census. METHODS: A five-step procedure was developed to identify predictive variables. Clinical expert (CE) thought processes comprised one model. Variables from that model were used to develop two mathematical models for the decision-support tool: an artificial neural network (ANN) and a multivariate logistic regression model (MLR). The ranking of the variables in the three models was compared using the Wilcoxon Signed Rank Test. The best performing model was used in a web-based decision-support tool with a user interface implemented in Hypertext Markup Language (HTML) and the mathematical model employing the ANN. RESULTS: CEs identified 51 potentially predictive variables for extubation decisions for an infant on mechanical ventilation. Comparisons of the three models showed a significant difference between the ANN and the CE (p = 0.0006). Of the original 51 potentially predictive variables, the 13 most predictive variables were used to develop an ANN as a web-based decision-tool. The ANN processes user-provided data and returns the prediction 0–1 score and a novelty index. The user then selects the most appropriate threshold for categorizing the prediction as a success or failure. Furthermore, the novelty index, indicating the similarity of the test case to the training case, allows the user to assess the confidence level of the prediction with regard to how much the new data differ from the data originally used for the development of the prediction tool. CONCLUSION: State-of-the-art, machine-learning methods can be employed for the development of sophisticated tools to aid clinicians' decisions. We identified numerous variables considered relevant for extubation decisions for mechanically ventilated premature infants with RDS. We then developed a web-based decision-support tool for clinicians which can be made widely available and potentially improve patient care world wide
LV reverse remodeling imparted by aortic valve replacement for severe aortic stenosis; is it durable? A cardiovascular MRI study sponsored by the American Heart Association
<p>Abstract</p> <p>Background</p> <p>In patients with severe aortic stenosis (AS), long-term data tracking surgically induced effects of afterload reduction on reverse LV remodeling are not available. Echocardiographic data is available short term, but in limited fashion beyond one year. Cardiovascular MRI (CMR) offers the ability to serially track changes in LV metrics with small numbers due to its inherent high spatial resolution and low variability.</p> <p>Hypothesis</p> <p>We hypothesize that changes in LV structure and function following aortic valve replacement (AVR) are detectable by CMR and once triggered by AVR, continue for an extended period.</p> <p>Methods</p> <p>Tweny-four patients of which ten (67 ± 12 years, 6 female) with severe, but compensated AS underwent CMR pre-AVR, 6 months, 1 year and up to 4 years post-AVR. 3D LV mass index, volumetrics, LV geometry, and EF were measured.</p> <p>Results</p> <p>All patients survived AVR and underwent CMR 4 serial CMR's. LVMI markedly decreased by 6 months (157 ± 42 to 134 ± 32 g/m<sup><b>2</b></sup>, p < 0.005) and continued trending downwards through 4 years (127 ± 32 g/m<sup><b>2</b></sup>). Similarly, EF increased pre to post-AVR (55 ± 22 to 65 ± 11%,(p < 0.05)) and continued trending upwards, remaining stable through years 1-4 (66 ± 11 vs. 65 ± 9%). LVEDVI, initially high pre-AVR, decreased post-AVR (83 ± 30 to 68 ± 11 ml/m2, p < 0.05) trending even lower by year 4 (66 ± 10 ml/m<sup><b>2</b></sup>). LV stroke volume increased rapidly from pre to post-AVR (40 ± 11 to 44 ± 7 ml, p < 0.05) continuing to increase non-significantly through 4 years (49 ± 14 ml) with these LV metrics paralleling improvements in NYHA. However, LVmass/volume, a 3D measure of LV geometry, remained unchanged over 4 years.</p> <p>Conclusion</p> <p>After initial beneficial effects imparted by AVR in severe AS patients, there are, as expected, marked improvements in LV reverse remodeling. Via CMR, surgically induced benefits to LV structure and function are durable and, unexpectedly express continued, albeit markedly incomplete improvement through 4 years post-AVR concordant with sustained improved clinical status. This supports down-regulation of both mRNA and MMP activity acutely with robust suppression long term.</p
Abstract Reasoning and Friendship in High Functioning Preadolescents with Autism Spectrum Disorders
To investigate the relationship between cognitive and social functioning, 20 Israeli individuals with HFASD aged 8–12 and 22 age, maternal education, and receptive vocabulary–matched preadolescents with typical development (TYP) came to the lab with a close friend. Measures of abstract reasoning, friendship quality, and dyadic interaction during a play session were obtained. As hypothesized, individuals with HFASD were significantly impaired in abstract reasoning, and there were significant group differences in friend and observer reports of friendship quality. There also was consistency in reports between friends. Two factors—“relationship appearance” and “relationship quality” described positive aspects of the relationships. Disability status and age related to relationship appearance. Proband abstract reasoning was related to relationship quality
Mammalian cell entry genes in Streptomyces may provide clues to the evolution of bacterial virulence
Understanding the evolution of virulence is key to appreciating the role specific loci play in pathogenicity. Streptomyces species are generally non-pathogenic soil saprophytes, yet within their genome we can find homologues of virulence loci. One example of this is the mammalian cell entry (mce) locus, which has been characterised in Mycobacterium tuberculosis. To investigate the role in Streptomyces we deleted the mce locus and studied its impact on cell survival, morphology and interaction with other soil organisms. Disruption of the mce cluster resulted in virulence towards amoebae (Acanthamoeba polyphaga) and reduced colonization of plant (Arabidopsis) models, indicating these genes may play an important role in Streptomyces survival in the environment. Our data suggest that loss of mce in Streptomyces spp. may have profound effects on survival in a competitive soil environment, and provides insight in to the evolution and selection of these genes as virulence factors in related pathogenic organisms
Teratogenicity of depleted uranium aerosols: A review from an epidemiological perspective
BACKGROUND: Depleted uranium is being used increasingly often as a component of munitions in military conflicts. Military personnel, civilians and the DU munitions producers are being exposed to the DU aerosols that are generated. METHODS: We reviewed toxicological data on both natural and depleted uranium. We included peer reviewed studies and gray literature on birth malformations due to natural and depleted uranium. Our approach was to assess the "weight of evidence" with respect to teratogenicity of depleted uranium. RESULTS: Animal studies firmly support the possibility that DU is a teratogen. While the detailed pathways by which environmental DU can be internalized and reach reproductive cells are not yet fully elucidated, again, the evidence supports plausibility. To date, human epidemiological data include case examples, disease registry records, a case-control study and prospective longitudinal studies. DISCUSSION: The two most significant challenges to establishing a causal pathway between (human) parental DU exposure and the birth of offspring with defects are: i) distinguishing the role of DU from that of exposure to other potential teratogens; ii) documentation on the individual level of extent of parental DU exposure. Studies that use biomarkers, none yet reported, can help address the latter challenge. Thoughtful triangulation of the results of multiple studies (epidemiological and other) of DU teratogenicity contributes to disentangling the roles of various potentially teratogenic parental exposures. This paper is just such an endeavor. CONCLUSION: In aggregate the human epidemiological evidence is consistent with increased risk of birth defects in offspring of persons exposed to DU
Dietary Restriction Depends on Nutrient Composition to Extend Chronological Lifespan in Budding Yeast Saccharomyces cerevisiae
10.1371/journal.pone.0064448PLoS ONE85
Synthetic microparticles conjugated with VEGF165 improve the survival of endothelial progenitor cells via microRNA-17 inhibition
Several cell-based therapies are under pre-clinical and clinical evaluation for the treatment of ischemic diseases. Poor survival and vascular engraftment rates of transplanted cells force them to work mainly via time-limited paracrine actions. Although several approaches, including the use of soluble vascular endothelial growth factor (sVEGF)-VEGF165, have been developed in the last 10 years to enhance cell survival, they showed limited efficacy. Here, we report a pro-survival approach based on VEGF-immobilized microparticles (VEGF-MPs). VEGF-MPs prolong VEGFR-2 and Akt phosphorylation in cord blood-derived late outgrowth endothelial progenitor cells (OEPCs). In vivo, OEPC aggregates containing VEGF-MPs show higher survival than those treated with sVEGF. Additionally, VEGF-MPs decrease miR-17 expression in OEPCs, thus increasing the expression of its target genes CDKN1A and ZNF652. The therapeutic effect of OEPCs is improved in vivo by inhibiting miR-17. Overall, our data show an experimental approach to improve therapeutic efficacy of proangiogenic cells for the treatment of ischemic diseases.Soluble vascular endothelial growth factor (VEGF) enhances vascular engraftment of transplanted cells but the efficacy is low. Here, the authors show that VEGF-immobilized microparticles prolong survival of endothelial progenitors in vitro and in vivo by downregulating miR17 and upregulating CDKN1A and ZNF652
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