Artificial Neural Network Inference (ANNI): A Study on Gene-Gene Interaction for Biomarkers in Childhood Sarcomas

Objective: To model the potential interaction between previously identified biomarkers in children sarcomas using artificial neural network inference (ANNI). Method: To concisely demonstrate the biological interactions between correlated genes in an interaction network map, only 2 types of sarcomas in the children small round blue cell tumors (SRBCTs) dataset are discussed in this paper. A backpropagation neural network was used to model the potential interaction between genes. The prediction weights and signal directions were used to model the strengths of the interaction signals and the direction of the interaction link between genes. The ANN model was validated using Monte Carlo cross-validation to minimize the risk of over-fitting and to optimize generalization ability of the model. Results: Strong connection links on certain genes (TNNT1 and FNDC5 in rhabdomyosarcoma (RMS); FCGRT and OLFM1 in Ewing’s sarcoma (EWS)) suggested their potency as central hubs in the interconnection of genes with different functionalities. The results showed that the RMS patients in this dataset are likely to be congenital and at low risk of cardiomyopathy development. The EWS patients are likely to be complicated by EWS-FLI fusion and deficiency in various signaling pathways, including Wnt, Fas/Rho and intracellular oxygen. Conclusions: The ANN network inference approach and the examination of identified genes in the published literature within the context of the disease highlights the substantial influence of certain genes in sarcomas

Teacher Wellbeing: The Importance of Teacher–Student Relationships

Many studies have examined the importance of teacher-student relationships for the development of children. Much less is known, however, about how these relationships impact the professional and personal lives of teachers. This review considers the importance of teacher-student relationships for the wellbeing of teachers guided by the Transactional Model of Stress and Coping of Lazarus (1991). Based on theories on interpersonal relationships, it is postulated that teachers have a basic need for relatedness with the students in their class that originates from the close proximity between teacher and student. It is discussed that teachers internalize experiences with students in representational models of relationships that guide emotional responses in daily interactions with students, and changes teacher wellbeing in the long run. In addition, the notion of mental representations of relationships at different levels of generalization could offer a window to understand how individual teacher-student relationships may affect the professional and personal self-esteem of teachers. Lastly, it is argued that the influence of student misbehavior on teacher stress may be more fully understood from a relationship perspective. The review shows that few studies have directly tested these propositions and offers suggestions for future research

The Early Positive Approaches to Support (E-PAtS) study: study protocol for a feasibility cluster randomised controlled trial of a group programme (E-PAtS) for family caregivers of young children with intellectual disability

Background: Children with intellectual disability have an IQ < 70, associated deficits in adaptive skills and are at increased risk of having clinically concerning levels of behaviour problems. In addition, parents of children with intellectual disability are likely to report high levels of mental health and other psychological problems. The Early Positive Approaches to Support (E-PAtS) programme for family caregivers of young children (5 years and under) with intellectual and developmental disabilities is a group-based intervention which aims to enhance parental psychosocial wellbeing and service access and support positive development for children. The aim of this study is to assess the feasibility of delivering E-PAtS to family caregivers of children with intellectual disability by community parenting support service provider organisations. The study will inform a potential, definitive RCT of the effectiveness and cost-effectiveness of E-PAtS. Methods: This study is a feasibility cluster randomised controlled trial, with embedded process evaluation. Up to 2 family caregivers will be recruited from 64 families with a child (18 months to 5 years) with intellectual disability at research sites in the UK. Participating families will be allocated to intervention: control on a 1:1 basis; intervention families will be offered the E-PAtS programme immediately, continuing to receive usual practice, and control participants will be offered the opportunity to attend the E-PAtS programme at the end of the follow-up period and will continue to receive usual practice. Data will be collected at baseline, 3 months post-randomisation and 12 months post-randomisation. The primary aim is to assess feasibility via the assessment of: recruitment of service provider organisations; participant recruitment; randomisation; retention; intervention adherence; intervention fidelity and the views of participants, intervention facilitators and service provider organisations regarding intervention delivery and study processes. The secondary aim is preliminary evaluation of a range of established outcome measures for individual family members, subsystem relationships and overall family functioning, plus additional health economic outcomes for inclusion in a future definitive trial. Discussion: The results of this study will inform a potential future definitive trial, to evaluate the effectiveness and cost-effectiveness of the E-PAtS intervention to improve parental psychosocial wellbeing. Such a trial would have significant scientific impact internationally in the intellectual disability field

Single Parenting and Child Behavior Problems in Kindergarten

Two waves of data from a sample of 89 poor and near-poor single black mothers and their preschool children were used to study the influences of parenting stress, physical discipline practices, and nonresident fathers’ relations with their children on behavior problems in kindergarten. The results indicate that higher levels of parent stress, more frequent spanking, and less frequent father–child contact at time 1 were associated with increased teacher-reported behavior problems at time 2. In addition, more frequent contact between nonresident biological fathers and their children moderated the negative effect of harsh discipline by mothers on subsequent child behavior problems. Specifically, when contact with the father was low, maternal spanking resulted in elevated levels of behavior problems; with average contact, this negative effect of spanking was muted; and with high contact, spanking was not associated with increased behavior problems in kindergarten. The implications of these findings for future research and policy are discussed

Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that primarily affects the lining of the synovial joints and is associated with progressive disability, premature death, and socioeconomic burdens. A better understanding of how the pathological mechanisms drive the deterioration of RA progress in individuals is urgently required in order to develop therapies that will effectively treat patients at each stage of the disease progress. Here we dissect the etiology and pathology at specific stages: (i) triggering, (ii) maturation, (iii) targeting, and (iv) fulminant stage, concomitant with hyperplastic synovium, cartilage damage, bone erosion, and systemic consequences. Modern pharmacologic therapies (including conventional, biological, and novel potential small molecule disease-modifying anti-rheumatic drugs) remain the mainstay of RA treatment and there has been significant progress toward achieving disease remission without joint deformity. Despite this, a significant proportion of RA patients do not effectively respond to the current therapies and thus new drugs are urgently required. This review discusses recent advances of our  understanding of RA pathogenesis, disease modifying drugs, and provides perspectives on next generation therapeutics for RA

Spatio-temporal patterns of event-related potentials related to audiovisual synchrony judgments in older adults

Older adults have altered perception of the relative timing between auditory and visual stimuli, even when stimuli are scaled to equate detectability. To help understand why, this study investigated the neural correlates of audiovisual synchrony judgments in older adults using electroencephalography (EEG). Fourteen younger (18-32 year old) and 16 older (61-74 year old) adults performed an audiovisual synchrony judgment task on flash-pip stimuli while EEG was recorded. All participants were assessed to have healthy vision and hearing for their age. Observers responded to whether audiovisual pairs were perceived as synchronous or asynchronous via a button press. The results showed that the onset of predictive sensory information for synchrony judgments was not different between groups. Channels over auditory areas contributed more to this predictive sensory information than visual areas. The spatial-temporal profile of the EEG activity also indicates that older adults used different resources to maintain a similar level of performance in audiovisual synchrony judgments compared with younger adults

Neuronal and glial cell expression of angiotensin II type 1 (AT1) and type 2 (AT2) receptors in the rat retina.

The bio-active peptide, angiotensin II (Ang II), has been suggested to exert a neuromodulatory effect on inner retinal neurons. In this study, we examined the distribution of angiotensin receptors (ATRs) in the developing and mature rat retina and optic nerve using immunofluorescence immunocytochemistry. Double-labeling experiments were performed with established markers to identify different retinal cell populations. In adult retinae, ATRs were observed on neurons involved in "ON" pathways of neurotransmission. Angiotensin II type 1 receptors (AT(1)Rs) were expressed by a sub-population of "ON" cone bipolar cells that also labeled for G alpha(0) and islet-1. Extra-neuronal expression of AT(1)Rs was evident on retinal astrocytes, Müller cells and blood vessels. Immunoreactivity for the angiotensin II type 2 receptor (AT(2)R) was observed on conventional and displaced GABAergic amacrine cells. Co-localization studies showed that AT(2)R-expressing amacrine cells constituted at least two separate sub-populations. Cell counts revealed that all wide-field amacrine cells expressing protein kinase C-alpha were also AT(2)R-positive; a further subset of amacrine cells expressing AT(2)Rs and stratifying in sublamina "b" of the inner plexiform layer (IPL) was identified. Developmental expression of AT(1)Rs was dynamic, involving multiple inner neuronal classes. At postnatal day 8 (P8), AT(1)R immunoreactivity was observed on putative ganglion cells. The characteristic bipolar cell labeling observed in adults was not evident until P13. In contrast, AT(2)Rs were detected as early as P2 and localized specifically to amacrine cells from this age onward. These data provide further evidence for the potential role of angiotensin II in the modulation of retinal neurons and glia. The differential pattern of expression of these receptors across these cell types is similar to that observed in the brain and suggests that a similar functional role for Ang II may also exist within the retina

Appraising the Quality of Systematic Reviews for Age-Related Macular Degeneration Interventions A Systematic Review

Importance: Age-related macular degeneration (AMD) is a leading cause of vision impairment. It is imperative that AMD care is timely, appropriate, and evidence-based. It is thus essential that AMD systematic reviews are robust; however, little is known about the quality of this literature. Objectives: To investigate the methodological quality of systematic reviews of AMD intervention studies, and to evaluate their use for guiding evidence-based care. Evidence Review: This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. All studies that self-identified as a systematic review in their title or abstract or were categorized as a systematic review from a medical subject heading and investigated the safety, efficacy and/or effectiveness of an AMD intervention were included. Comprehensive electronic searches were performed in Ovid MEDLINE, Embase, and the Cochrane Library from inception to March 2017. Two reviewers independently assessed titles and abstracts, then full-texts for eligibility. Quality was assessed using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) tool. Study characteristics (publication year, type of intervention, journal, citation rate, and funding source) were extracted. Findings: Of 983 citations retrieved, 71 studies (7.6%) were deemed eligible. The first systematic review relating to an AMD intervention was published in 2003. More than half were published since 2014. Methodological quality was highly variable. The mean (SD) AMSTAR score was 5.8 (3.2) of 11.0, with no significant improvement over time (r = -0.03; 95% CI, -0.26 to 0.21; P = .83). Cochrane systematic reviews were overall of higher quality than reviews in other journals (mean [SD] AMSTAR score, 9.9 [1.2], n = 15 vs 4.7 [2.2], n = 56; P < .001). Overall, there was poor adherence to referring to an a priori design (22 articles [31%]) and reporting conflicts of interest in both the review and included studies (16 articles [23%]). Reviews funded by government grants and/or institutions were generally of higher quality than industry-sponsored reviews or where the funding source was not reported. Conclusions and Relevance: There are gaps in the conduct of systematic reviews in the field of AMD. Enhanced endorsement of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement by refereed journals may improve review quality and improve the dissemination of reliable evidence relating to AMD interventions to clinicians