Measuring disadvantage in the early years in the UK: A systematic scoping review

Background: The relationship between disadvantage and child health in the early years is well established. For this evidence base to most helpfully inform services, we need to better understand how disadvantage is conceptualised and measured in the literature. We aimed to conceptualise disadvantage measured in child health literature and explore the associations between disadvantage and child health using these measures. Method: We conducted a scoping review using systematic methods to identify key concepts of disadvantage used in empirical child health literature. We searched MEDLINE, Scopus, and grey literature for studies exploring the association between disadvantage and child health outcomes for children aged 0-5 in the United Kingdom. We extracted and analysed data from 86 studies. Results: We developed a framework describing two domains, each with two attributes conceptualising disadvantage: level of disadvantage indicator (individual and area) and content of disadvantage indicator (social and economic). Individual-level measures of disadvantage tended to identify stronger associations between disadvantage and child health compared with area-level measures. Conclusion: The choice of disadvantage indicators, particularly whether individual- or area-level, can affect the inferences made about the relationship between disadvantage and child health. Better access to individual-level disadvantage indicators in administrative data could support development and implementation of interventions aimed at reducing child health inequalities in the early years

Why Should ACT Work When CBT Has Failed? a Study Assessing Acceptability and Feasibility of Acceptance and Commitment Therapy (ACT) for Paediatric Patients With Chronic Fatigue Syndrome/myalgic Encephalomyelitis (CFS/ME)

AIMS: Paediatric chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) effects 0.5–3.28% of children. NICE guidance recommends Activity Management, Graded Exercise Therapy or Cognitive Behavioural Therapy for fatigue (CBT-f). Approximately 15% of patients do not achieve full recovery within one year with current treatments. Acceptance and Commitment Therapy (ACT) is an effective treatment in many chronic illnesses. There are no studies investigating ACT for paediatric CFS/ME. This feasability study aimed to assess if ACT is a feasible and acceptable alternative treatment when current treatment has not led to recovery. METHODS: This feasability cohort study aimed to enrol a minimum of 12 participants aged 11–18 yearswith CFS/ME attending the Royal United Hospitals Bath NHS Foundation Trust Specialist Paediatric CFS/ME Service, who were still symptomatic after 12 months or 12 sessions of standard treatment and were offered six to 12 sessions of ACT. Retention and recruitment data were analysed. Participants were asked to complete questionnaires before, during and after treatment. A selection of participants and their parents were interviewed about their experience of the study. Interviews were analysed using thematic analysis. RESULTS: 19 participants (95% of those approached) were recruited. Only 4 participants of this hard-to-reach group did not complete treatment. In almost all sessions participants reported that they felt ‘totally’ listened to in post session questionnaires (31/33 sessions). Preliminary interviews (n = 12) indicate acceptability of ACT, with all young people and their parents stating that they thought ACT should be offered to this population. Participants particularly commented that the absence of thought challenging (used in CBT-f) was a positive element of ACT. Participant's openness to try new approaches and altruistic desire to be in a study was noted. CONCLUSION: Recruitment data indicate that it is feasible to recruit and retain 11–18-year-olds with CFS/ME to a study offering ACT. Interviews with participants and parents were broadly positive suggesting ACT is an acceptable treatment in this population. Results indicated that it is both feasible and acceptable to offer ACT to 11–18-year-olds with CFS/ME using this protocol, supporting the prospect of an RCT in this area

Structure-based prediction of RNA-binding domains and RNA-binding sites and application to structural genomics targets

Mechanistic understanding of many key cellular processes often involves identification of RNA binding proteins (RBPs) and RNA binding sites in two separate steps. Here, they are predicted simultaneously by structural alignment to known protein–RNA complex structures followed by binding assessment with a DFIRE-based statistical energy function. This method achieves 98% accuracy and 91% precision for predicting RBPs and 93% accuracy and 78% precision for predicting RNA-binding amino-acid residues for a large benchmark of 212 RNA binding and 6761 non-RNA binding domains (leave-one-out cross-validation). Additional tests revealed that the method makes no false positive prediction from 311 DNA binding domains but correctly detects six domains binding with both DNA and RNA. In addition, it correctly identified 31 of 75 unbound RNA-binding domains with 92% accuracy and 65% precision for predicted binding residues and achieved 86% success rate in its application to SCOP RNA binding domain superfamily (Structural Classification Of Proteins). It further predicts 25 targets as RBPs in 2076 structural genomics targets: 20 of 25 predicted ones (80%) are putatively RNA binding. The superior performance over existing methods indicates the importance of dividing structures into domains, using a Z-score to measure relative structural similarity, and a statistical energy function to measure protein–RNA binding affinity

Binding to SMN2 pre-mRNA-protein complex elicits specificity for small molecule splicing modifiers

Small molecule splicing modifiers have been previously described that target the general splicing machinery and thus have low specificity for individual genes. Several potent molecules correcting the splicing deficit of the SMN2 (survival of motor neuron 2) gene have been identified and these molecules are moving towards a potential therapy for spinal muscular atrophy (SMA). Here by using a combination of RNA splicing, transcription, and protein chemistry techniques, we show that these molecules directly bind to two distinct sites of the SMN2 pre-mRNA, thereby stabilizing a yet unidentified ribonucleoprotein (RNP) complex that is critical to the specificity of these small molecules for SMN2 over other genes. In addition to the therapeutic potential of these molecules for treatment of SMA, our work has wide-ranging implications in understanding how small molecules can interact with specific quaternary RNA structures

RBPDB: a database of RNA-binding specificities

The RNA-Binding Protein DataBase (RBPDB) is a collection of experimental observations of RNA-binding sites, both in vitro and in vivo, manually curated from primary literature. To build RBPDB, we performed a literature search for experimental binding data for all RNA-binding proteins (RBPs) with known RNA-binding domains in four metazoan species (human, mouse, fly and worm). In total, RPBDB contains binding data on 272 RBPs, including 71 that have motifs in position weight matrix format, and 36 sets of sequences of in vivo-bound transcripts from immunoprecipitation experiments. The database is accessible by a web interface which allows browsing by domain or by organism, searching and export of records, and bulk data downloads. Users can also use RBPDB to scan sequences for RBP-binding sites. RBPDB is freely available, without registration at http://rbpdb.ccbr.utoronto.ca/

Incidence of Resident Mistreatment in the Learning Environment Across Three Institutions

Introduction: Mistreatment in the learning environment is associated with negative outcomes for trainees. While the Association of American Medical Colleges (AAMC) annual Graduation Questionnaire (GQ) has collected medical student reports of mistreatment for a decade, there is not a similar nationally benchmarked survey for residents. The objective of this study is to explore the prevalence of resident experiences with mistreatment. Methods: Residents at three academic institutions were surveyed using questions similar to the GQ in 2018. Quantitative data were analyzed based on frequency and Mann-Whitney U tests to detect gender differences. Results: Nine hundred ninety-six of 2682 residents (37.1%) responded to the survey. Thirty-nine percent of residents reported experiencing at least one incident of mistreatment. The highest reported incidents were public humiliation (23.7%) and subject to offensive sexist remarks/comments (16.0%). Female residents indicated experiencing significantly more incidents of: public embarrassment, public humiliation, offensive sexist remarks, lower evaluations based on gender, denied opportunities for training or rewards, and unwanted sexual advances. Faculty were the most frequent instigators of mistreatment (66.4%). Of trainees who reported experiencing mistreatment, less than one-quarter reported the behavior. Conclusion: Mistreatment in the academic learning environment is a concern in residency programs. There is increased frequency among female residents

Analysis of interactions between ribosomal proteins and RNA structural motifs

<p>Abstract</p> <p>Background</p> <p>One important goal of structural bioinformatics is to recognize and predict the interactions between protein binding sites and RNA. Recently, a comprehensive analysis of ribosomal proteins and their interactions with rRNA has been done. Interesting results emerged from the comparison of r-proteins within the small subunit in <it>T. thermophilus </it>and <it>E. coli</it>, supporting the idea of a core made by both RNA and proteins, conserved by evolution. Recent work showed also that ribosomal RNA is modularly composed. Motifs are generally single-stranded sequences of consecutive nucleotides (ssRNA) with characteristic folding. The role of these motifs in protein-RNA interactions has been so far only sparsely investigated.</p> <p>Results</p> <p>This work explores the role of RNA structural motifs in the interaction of proteins with ribosomal RNA (rRNA). We analyze composition, local geometries and conformation of interface regions involving motifs such as tetraloops, kink turns and single extruded nucleotides. We construct an interaction map of protein binding sites that allows us to identify the common types of shared 3-D physicochemical binding patterns for tetraloops. Furthermore, we investigate the protein binding pockets that accommodate single extruded nucleotides either involved in kink-turns or in arbitrary RNA strands. This analysis reveals a new structural motif, called <it>tripod</it>.</p> <p>It corresponds to small pockets consisting of three aminoacids arranged at the vertices of an almost equilateral triangle. We developed a search procedure for the recognition of tripods, based on an empirical tripod fingerprint.</p> <p>Conclusion</p> <p>A comparative analysis with the overall RNA surface and interfaces shows that contact surfaces involving RNA motifs have distinctive features that may be useful for the recognition and prediction of interactions.</p

Brave new brains: sociology, family and the politics of knowledge

This article critically explores sociological arguments for greater biosocial synthesis, centring contemporary developments in public policy to demonstrate how such a reframing of humanity tends to reinforce existing political orders and socially patterned normativities. The case for further amalgamation of the social and life sciences is examined to suggest that production of somatic markers of truth from relational encounters largely relies upon an anaemic and politically contained version of the social as acquired in early childhood. More specifically, the gendered, classed and culturally specific practice of parenting children has come to occupy a new significance in accounts of social brains and environmentally reactive genomes. This is highlighted through a discussion of ‘early intervention’ as a heavily biologised policy rationale framing opportunities for biosocial collaboration. It is argued that late capitalist objectives of personal investment and optimisation are driving this assimilation of the social and life sciences, pursuing an agenda that traces and re-scores longstanding social divisions in the name of progress

Two Isoforms of the mRNA Binding Protein IGF2BP2 Are Generated by Alternative Translational Initiation

IGF2BP2 is a member of a family of mRNA binding proteins that, collectively, have been shown to bind to several different mRNAs in mammalian cells, including one of the mRNAs encoding insulin-like growth factor-2. Polymorphisms in the Igf2bp2 gene are associated with risk of developing type 2 diabetes, but detailed functional characterisation of IGF2BP2 protein is lacking. By immunoblotting with C-terminally reactive antibodies we identified a novel IGF2BP2 isoform with a molecular weight of 58 kDa in both human and rodents, that is expressed at somewhat lower levels than the full-length 65 kDa protein. We demonstrated by mutagenesis that this isoform is generated by alternative translation initiation at the internal Met69. It lacks a conserved N-terminal RNA Recognition Motif (RRM) and would be predicted to differ functionally from the canonical full length isoform. We further investigated IGF2BP2 mRNA transcripts by amplification of cDNA using 5′-RACE. We identified multiple transcription start sites of the human, mouse and rat Igf2bp2 genes in a highly conserved region only 50–90 nts upstream of the major translation start site, ruling out the existence of N-terminally extended isoforms. We conclude that structural heterogeneity of IGF2BP2 protein should be taken into account when considering cellular function

Visual mismatch negativity to masked stimuli presented at very brief presentation rates

Mismatch Negativity (MMN) has been characterised as a ‘pre-attentive’ component of an event-related potential (ERP) that is related to discrimination and error prediction processes. The aim of the current experiment was to establish whether visual MMN could be recorded to briefly presented, backward and forward masked visual stimuli, given both below and above levels of subjective experience. Evidence of visual MMN elicitation in the absence of the ability to consciously report stimuli would provide strong evidence for the automaticity of the visual MMN mechanism. Using an oddball paradigm, two stimuli that differed in orientation from each other, an + and an x were presented on a computer screen. Electroencephalogram (EEG) was recorded from nine participants (six females), mean age 21.4 years. Results showed that for stimuli that were effectively masked at 7ms presentation, there was little variation in the ERPs evoked to standard and deviant stimuli or in the subtraction waveform employed to delineate the visual MMN. At 14 ms stimulus presentation, when participants were able to report stimulus presence, an enhanced negativity at around 175 ms and 305 ms was observed to the deviant and was evident in the subtraction waveform. Although some of the difference observed in the ERPs can be attributed to stimulus characteristics, the use of a ‘lonely’ deviant protocol revealed attenuated visual MMN components at 14 ms stimulus presentation. Overall, results suggest that some degree of conscious attention is required before visual MMN components emerge, suggesting visual MMN is not an entirely pre-attentive process