A cross-lagged analysis of emotion regulation, peer problems and emotional problems in children with and without early language difficulties: Evidence from the Millennium Cohort Study

Purpose: Adolescents with a history of language difficulties are at risk for increased social and emotional difficulties; however, the pathways involved are unclear. We examine the contribution of poor emotion regulation by comparing longitudinal data from children at risk of developmental language disorder (rDLD) and the general population. Method: Data from the Millennium Cohort Study were analyzed at ages 3, 5, 7, 11, and 14 years. The rDLD group (children with parent-reported difficulties and/or a score of −1.5 SDs on the Naming Vocabulary subtest at age 5 years) was compared to a general population group on parent reports of emotion regulation, peer problems, and emotional problems. Results: In line with the established literature, increased socioemotional problems in individuals with language difficulties were reported. Poor emotion regulation consistently predicted subsequent peer and emotional problems throughout development in both groups. Stronger cross-lag effects were found in the rDLD group for poor emotion regulation at age 3 years predicting age 5 years emotional problems and age 5 years emotional problems predicting age 7 years emotion regulation difficulties. Stronger reciprocal cross-lag effects were also observed in the rDLD group between peer and emotional problems at ages 3 and 5 years. No significant group differences were found in adolescence. Conclusions: Poor emotion regulation makes a small but significant contribution to later peer and emotional difficulties, and this relationship is stronger in children at rDLD. Early reciprocal peer and emotional difficulties are also stronger in the rDLD group, but these effects dissipate in midchildhood. Nevertheless, the consistent relationship between early emotion regulation difficulties and socioemotional problems throughout development warrants further investigation in individuals with lower language skills

Co-opetition models for governing professional football

In recent years, models for co-creating value in a business-to-business context have often been examined with the aim of studying the strategies implemented by and among organisations for competitive and co-operative purposes. The traditional concepts of competition and co-operation between businesses have now evolved, both in terms of the sector in which the businesses operate and in terms of the type of goods they produce. Many researchers have, in recent times, investigated the determinants that can influence the way in which the model of co-opetition can be applied to the football world. Research interest lies in the particular features of what makes a good football. In this paper, the aim is to conduct an analysis of the rules governing the “football system”, while also looking at the determinants of the demand function within football entertainment. This entails applying to football match management the co-opetition model, a recognised model that combines competition and co-operation with the view of creating and distributing value. It can, therefore, be said that, for a spectator, watching sport is an experience of high suspense, and this suspense, in turn, depends upon the degree of uncertainty in the outcome. It follows that the rules ensuring that both these elements can be satisfied are a fertile ground for co-operation between clubs, as it is in the interest of all stakeholders to offer increasingly more attractive football, in comparison with other competing products. Our end purpose is to understand how co-opetition can be achieved within professional football

The relationship between the systemic inflammatory response, tumour proliferative activity, T-lymphocytic and macrophage infiltration, microvessel density and survival in patients with primary operable breast cancer

The significance of the inter-relationship between tumour and host local/systemic inflammatory responses in primary operable invasive breast cancer is limited. The inter-relationship between the systemic inflammatory response (pre-operative white cell count, C-reactive protein and albumin concentrations), standard clinicopathological factors, tumour T-lymphocytic (CD4+ and CD8+) and macrophage (CD68+) infiltration, proliferative (Ki-67) index and microvessel density (CD34+) was examined using immunohistochemistry and slide-counting techniques, and their prognostic values were examined in 168 patients with potentially curative resection of early-stage invasive breast cancer. Increased tumour grade and proliferative activity were associated with greater tumour T-lymphocyte (P<0.05) and macrophage (P<0.05) infiltration and microvessel density (P<0.01). The median follow-up of survivors was 72 months. During this period, 31 patients died; 18 died of their cancer. On univariate analysis, increased lymph-node involvement (P<0.01), negative hormonal receptor (P<0.10), lower albumin concentrations (P<0.01), increased tumour proliferation (P<0.05), increased tumour microvessel density (P<0.05), the extent of locoregional control (P<0.0001) and limited systemic treatment (Pless than or equal to0.01) were associated with cancer-specific survival. On multivariate analysis of these significant covariates, albumin (HR 4.77, 95% CI 1.35–16.85, P=0.015), locoregional treatment (HR 3.64, 95% CI 1.04–12.72, P=0.043) and systemic treatment (HR 2.29, 95% CI 1.23–4.27, P=0.009) were significant independent predictors of cancer-specific survival. Among tumour-based inflammatory factors, only tumour microvessel density (P<0.05) was independently associated with poorer cancer-specific survival. The host inflammatory responses are closely associated with poor tumour differentiation, proliferation and malignant disease progression in breast cancer

Mutation in the FUS nuclear localisation signal domain causes neurodevelopmental and systemic metabolic alterations

Variants in the ubiquitously expressed DNA/RNA-binding protein FUS cause aggressive juvenile forms of amyotrophic lateral sclerosis (ALS). Most FUS mutation studies have focused on motor neuron degeneration; little is known about wider systemic or developmental effects. We studied pleiotropic phenotypes in a physiological knock-in mouse model carrying the pathogenic FUSDelta14 mutation in homozygosity. RNA sequencing of multiple organs aimed to identify pathways altered by the mutant protein in the systemic transcriptome, including metabolic tissues, given the link between ALS-frontotemporal dementia and altered metabolism. Few genes were commonly altered across all tissues, and most genes and pathways affected were generally tissue specific. Phenotypic assessment of mice revealed systemic metabolic alterations related to the pathway changes identified. Magnetic resonance imaging brain scans and histological characterisation revealed that homozygous FUSDelta14 brains were smaller than heterozygous and wild-type brains and displayed significant morphological alterations, including a thinner cortex, reduced neuronal number and increased gliosis, which correlated with early cognitive impairment and fatal seizures. These findings show that the disease aetiology of FUS variants can include both neurodevelopmental and systemic alterations

Personalized Pathway Enrichment Map of Putative Cancer Genes from Next Generation Sequencing Data

BACKGROUND: Pathway analysis of a set of genes represents an important area in large-scale omic data analysis. However, the application of traditional pathway enrichment methods to next-generation sequencing (NGS) data is prone to several potential biases, including genomic/genetic factors (e.g., the particular disease and gene length) and environmental factors (e.g., personal life-style and frequency and dosage of exposure to mutagens). Therefore, novel methods are urgently needed for these new data types, especially for individual-specific genome data. METHODOLOGY: In this study, we proposed a novel method for the pathway analysis of NGS mutation data by explicitly taking into account the gene-wise mutation rate. We estimated the gene-wise mutation rate based on the individual-specific background mutation rate along with the gene length. Taking the mutation rate as a weight for each gene, our weighted resampling strategy builds the null distribution for each pathway while matching the gene length patterns. The empirical P value obtained then provides an adjusted statistical evaluation. PRINCIPAL FINDINGS/CONCLUSIONS: We demonstrated our weighted resampling method to a lung adenocarcinomas dataset and a glioblastoma dataset, and compared it to other widely applied methods. By explicitly adjusting gene-length, the weighted resampling method performs as well as the standard methods for significant pathways with strong evidence. Importantly, our method could effectively reject many marginally significant pathways detected by standard methods, including several long-gene-based, cancer-unrelated pathways. We further demonstrated that by reducing such biases, pathway crosstalk for each individual and pathway co-mutation map across multiple individuals can be objectively explored and evaluated. This method performs pathway analysis in a sample-centered fashion, and provides an alternative way for accurate analysis of cancer-personalized genomes. It can be extended to other types of genomic data (genotyping and methylation) that have similar bias problems

Differences in risk factors for children with special health care needs (CSHCN) receiving needed specialty care by socioeconomic status

<p>Abstract</p> <p>Background</p> <p>The purpose of this study is to identify factors affecting CSHCN's receiving needed specialty care among different socioeconomic levels. Previous literature has shown that Socioeconomic Status (SES) is a significant factor in CHSHCN receiving access to healthcare. Other literature has shown that factors of insurance, family size, race/ethnicity and sex also have effects on these children's receipt of care. However, this literature does not address whether other factors such as maternal education, geographic location, age, insurance type, severity of condition, or race/ethnicity have different effects on receiving needed specialty care for children in each SES level.</p> <p>Methods</p> <p>Data were obtained from the National Survey of Children with Special Health Care Needs, 2000–2002. The study analyzed the survey which studies whether CHSCN who needed specialty care received it. The analysis included demographic characteristics, geographical location of household, severity of condition, and social factors. Multiple logistic regression models were constructed for SES levels defined by federal poverty level: < 199%; 200–299%; ≥ 300%.</p> <p>Results</p> <p>For the poorest children (,199% FPL) being uninsured had a strong negative effect on receiving all needed specialty care. Being Hispanic was a protective factor. Having more than one adult in the household had a positive impact on receipt of needed specialty care but a larger number of children in the family had a negative impact. For the middle income group of children (200–299% of FPL severity of condition had a strong negative association with receipt of needed specialty care.</p> <p>Children in highest income group (> 300% FPL) were positively impacted by living in the Midwest and were negatively impacted by the mother having only some college compared to a four-year degree.</p> <p>Conclusion</p> <p>Factors affecting CSHCN receiving all needed specialty care differed among socioeconomic groups. These differences should be addressed in policy and practice. Future research should explore the CSHCN population by income groups to better serve this population</p

Implementation of a population-based epidemiological rare disease registry: study protocol of the amyotrophic lateral sclerosis (ALS) - registry Swabia

BACKGROUND: The social and medical impact of rare diseases is increasingly recognized. Amyotrophic lateral sclerosis (ALS) is the most prevalent of the motor neuron diseases. It is characterized by rapidly progressive damage to the motor neurons with a survival of 2–5 years for the majority of patients. The objective of this work is to describe the study protocol and the implementation steps of the amyotrophic lateral sclerosis (ALS) registry Swabia, located in the South of Germany. METHODS/DESIGN: The ALS registry Swabia started in October 2010 with both, the retrospective (01.10.2008-30.09.2010) and prospective (from 01.10.2010) collection of ALS cases, in a target population of 8.6 million persons in Southern Germany. In addition, a population based case–control study was implemented based on the registry that also included the collection of various biological materials. Retrospectively, 420 patients (222 men and 198 women) were identified. Prospectively data of ALS patients were collected, of which about 70% agreed to participate in the population-based case–control study. All participants in the case–control study provided also a blood sample. The prospective part of the study is ongoing. DISCUSSION: The ALS registry Swabia has been implemented successfully. In rare diseases such as ALS, the collaboration of registries, the comparison with external samples and biorepositories will facilitate to identify risk factors and to further explore the potential underlying pathophysiological mechanisms

The Comparative Oncology Trials Consortium: Using Spontaneously Occurring Cancers in Dogs to Inform the Cancer Drug Development Pathway

Chand Khanna and colleagues describe the work of the Comparative Oncology Trials Consortium (COTC), which provides infrastructure and resources to integrate naturally occurring dog cancer models into the development of new human cancer drugs, devices, and imaging techniques