Protocol for developing core outcome sets for evaluation of psychosocial interventions for children and families with experience or at risk of child maltreatment or domestic abuse

Introduction Recognition that child maltreatment (CM) and domestic violence and abuse (DVA) are common and have serious and long-term adverse health consequences has resulted in policies and programmes to ensure that services respond to and safeguard children and their families. However, high-quality evidence about how services can effectively intervene is scant. The value of the current evidence base is limited partly because of the variety of outcomes and measures used in evaluative studies. One way of addressing this limitation is to develop a core outcome set (COS) which is measured and reported as a minimum standard in the context of trials and other types of evaluative research. The study described in this protocol aims to develop two discrete COSs for use in future evaluation of psychosocial interventions aimed at improving outcomes for children and families at risk or with experience of (1) CM or (2) DVA. Methods and analysis A two-phase mixed methods design: (1) rapid reviews of evidence, stakeholder workshops and semistructured interviews with adult survivors of CM/DVA and parents of children who have experienced CM/DVA and (2) a three panel adapted E-Delphi Study and consensus meeting. This study protocol adheres to reporting guidance for COS protocols and has been registered on the Core Outcome Measures for Effectiveness Trials (COMET) database. Ethics and dissemination We will disseminate our findings through peer-reviewed and open access publications, the COMET website and presentations at international conferences. We will engage with research networks, journal editors and funding agencies to promote awareness of the CM-COS and DVA-COS. We will work with advisory and survivor and public involvement groups to coproduce a range of survivor, policy and practice facing outputs. Approval for this study has been granted by the Research Ethics Committee at University College London

Planar Airy beam light-sheet for two-photon microscopy

We demonstrate the first planar Airy light-sheet microscope. Fluorescence light-sheet microscopy has become the method of choice to study large biological samples with cellular or sub-cellular resolution. The propagation-invariant Airy beam enables a ten-fold increase in field-of-view with single-photon excitation; however, the characteristic asymmetry of the light-sheet limits its potential for multi-photon excitation. Here we show how a planar light-sheet can be formed from the curved propagation-invariant Airy beam. The resulting symmetric light sheet excites two-photon fluorescence uniformly across an extended field-of-view without the need for deconvolution. We demonstrate the method for rapid two-photon imaging of large volumes of neuronal tissue.Comment: 7 pages, 4 figure

Brain volume in chronic ketamine users - Relationship to sub-threshold psychotic symptoms and relevance to schizophrenia

RATIONALE: Ketamine may model aspects of schizophrenia arising through NMDA receptor activity deficits. Although acute ketamine can induce effects resembling both positive and negative psychotic symptoms, chronic use may be a closer model of idiopathic psychosis. OBJECTIVES: We tested the hypotheses that ketamine users had lower brain volumes, as measured using MRI, and greater sub-threshold psychotic symptoms relative to a poly-drug user control group. METHODS: Ketamine users (n = 17) and poly-drug using controls (n = 19) were included in the study. All underwent volumetric MRI imaging and measurement of sub-threshold psychotic symptoms using the Comprehensive Assessment of At-Risk Mental State (CAARMS). Freesurfer was used to analyse differences in regional brain volume, cortical surface area and thickness between ketamine users and controls. The relationship between CAARMS ratings and brain volume was also investigated in ketamine users. RESULTS: Ketamine users were found to have significantly lower grey matter volumes of the nucleus accumbens, caudate nucleus, cerebellum and total cortex (FDR p \u3c 0.05; Cohen\u27s d = 0.36-0.75). Within the cortex, ketamine users had significantly lower grey matter volumes within the frontal, temporal and parietal cortices (Cohen\u27s d 0.7-1.31; FDR p \u3c 0.05). They also had significantly higher sub-threshold psychotic symptoms (p \u3c 0.05). Frequency of ketamine use showed an inverse correlation with cerebellar volume (p \u3c 0.001), but there was no relationship between regional brain volumes and sub-threshold psychotic symptoms. CONCLUSIONS: Chronic ketamine use may cause lower grey matter volumes as well as inducing sub-threshold psychotic symptoms, although these likely arise through distinct mechanisms

The Importance of Grey and Qualitative Literature in Developing Domestic Violence and Abuse and Child Maltreatment Core Outcome Sets: A Brief Report

Purpose: Core Outcome Sets (COS) are agreed sets of outcomes to be used in all trials that evaluate the effect of interventions. This report considers the added value of including grey and qualitative literature in a study to identify COSs of family-focused interventions for CM and DVA. / Methods: We identified outcomes of interventions for DVA or CM through systematically searching 12 academic databases and 86 organisation websites, leading to the inclusion of 485 full-text reports across 6 reviews. We developed a candidate outcome longlist comprising 347 extracted outcomes. / Results: We identified 87% (282/347) of candidate outcomes from the grey and qualitative literature, and 37% (127/347) from the trial literature. Of the candidate outcomes on the longlist, 22% (75/347) were identified solely from the grey or qualitative literature and 7% (26/347) from trial literature. Three of the eight outcomes in the final core outcome sets may have been missed if grey or qualitative literature had not been searched. / Conclusions: The qualitative and grey literature adds DVA and CM outcomes that are relevant to survivor perspectives but not reported in trials; this had an impact on the final COSs. It is important for COS developers to consider what they may be missing if they do not search the qualitative and grey literature

Effect of early glycemic control on HbA1c tracking and development of vascular complications after 5 years of childhood onset type 1 diabetes: Systematic review and meta-analysis.

OBJECTIVE: A systematic review and meta-analysis was conducted to investigate if glycemic control measured by glycated hemoglobin (HbA1c) levels near diagnosis are predictive of future glycemic outcomes and vascular complications in childhood onset type 1 diabetes (T1D). METHODS: Evidence was gathered using electronic databases (MEDLINE, EMBASE, Web of Science, CINAHL, Scopus, and Cochrane Library up to February 2017) and snowballing techniques. Studies investigating the association between the exposure "early glycemic control" and main outcome: "tracking of early control" and secondary outcome: risk of future complications; in children and young people aged 0 to 19 years at baseline; were systematically double-reviewed, quality assessed, and outcome data extracted for synthesis and meta-analysis. FINDINGS: Five studies (N = 4227 participants) were eligible. HbA1c levels were sub-optimal throughout the study period but tended to stabilize in a "track" by 6 months after T1D diagnosis. The group with low HbA1c <53 mmol/mol (<7%) at baseline had lower long-term HbA1c levels than the higher HbA1c group. The estimated standardized mean difference between the sub groups showed a reduction of HbA1c levels on average by 1.6% (range -0.95% to -2.28%) from baseline. Only one study investigated the association between early glycemic control and development of vascular complications in childhood onset T1D. INTERPRETATIONS: Glycemic control after the first few months of childhood onset T1D, remains stable but sub-optimal for a decade. The low and high HbA1c levels at baseline seem to "track" in their respective tracks during the 10-year follow-up, however, the initial difference between groups narrows over time. PROSPERO: CRD42015024546 http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42015024546

Brain volume in chronic ketamine users — relationship to sub-threshold psychotic symptoms and relevance to schizophrenia

Rationale: Ketamine may model aspects of schizophrenia arising through NMDA receptor activity deficits. Although acute ketamine can induce effects resembling both positive and negative psychotic symptoms, chronic use may be a closer model of idiopathic psychosis. Objectives: We tested the hypotheses that ketamine users had lower brain volumes, as measured using MRI, and greater sub-threshold psychotic symptoms relative to a poly-drug user control group. Methods: Ketamine users (n = 17) and poly-drug using controls (n = 19) were included in the study. All underwent volumetric MRI imaging and measurement of sub-threshold psychotic symptoms using the Comprehensive Assessment of At-Risk Mental State (CAARMS). Freesurfer was used to analyse differences in regional brain volume, cortical surface area and thickness between ketamine users and controls. The relationship between CAARMS ratings and brain volume was also investigated in ketamine users. Results: Ketamine users were found to have significantly lower grey matter volumes of the nucleus accumbens, caudate nucleus, cerebellum and total cortex (FDR p < 0.05; Cohen’s d = 0.36–0.75). Within the cortex, ketamine users had significantly lower grey matter volumes within the frontal, temporal and parietal cortices (Cohen’s d 0.7–1.31; FDR p < 0.05). They also had significantly higher sub-threshold psychotic symptoms (p < 0.05). Frequency of ketamine use showed an inverse correlation with cerebellar volume (p < 0.001), but there was no relationship between regional brain volumes and sub-threshold psychotic symptoms. Conclusions: Chronic ketamine use may cause lower grey matter volumes as well as inducing sub-threshold psychotic symptoms, although these likely arise through distinct mechanisms

Climatic and vegetational drivers of insect beta diversity at the continental scale

Aim: We construct a framework for mapping pattern and drivers of insect diversity at the continental scale and use it to test whether and which environmental gradients drive insect beta diversity. Location: Global; North and Central America; Western Europe. Time period: 21st century. Major taxa studied: Insects. Methods: An informatics system was developed to integrate terrestrial data on insects with environmental parameters. We mined repositories of data for distribution, climatic data were retrieved (WorldClim), and vegetation parameters inferred from remote sensing analysis (MODIS Vegetation Continuous Fields). Beta diversity between sites was calculated and then modeled with two methods, Mantel test with multiple regression and generalized dissimilarity modeling. Results: Geographic distance was the main driver of insect beta diversity. Independent of geographic distance, bioclimate variables explained more variance in dissimilarity than vegetation variables, although the particular variables found to be significant were more consistent in the latter, particularly, tree cover. Tree cover gradients drove compositional dissimilarity at denser coverages, in both continental case studies. For climate, gradients in temperature parameters were significant in driving beta diversity more so than gradients in precipitation parameters. Main conclusions: Although environmental gradients drive insect beta diversity independently of geography, the relative contribution of different climatic and vegetational parameters is not expected to be consistent in different study systems. With further incorporation of additional temporal information and variables, this approach will enable the development of a predictive framework for conserving insect biodiversity at the global scale

Caries associated with orthodontic care part 2: management

It is recognized that wearing an orthodontic appliance increases the caries risk of the individual. The prevalence of demineralization has been reported to be as high as 73%. When demineralization occurs a number of treatments exist: fluoride application, acid microabrasion, casein phosphopeptide-amorphous calcium phosphate (CCP-ACP), resin infiltration and self-assembling peptides. Of these, topical fluoride has the most evidence to support its use. CPD/Clinical Relevance: Demineralization is the most common complication of orthodontic care. The clinician should understand how to manage this when it occurs

Salivary cortisol, cortisone and serum cortisol concentrations are related to age and body mass index in healthy children and young people

Background Saliva is an ideal medium in which to measure cortisol in children. However, there are very few data reporting salivary cortisol or cortisone concentrations in healthy children since the introduction of liquid chromatography mass spectrometry (LC MS/MS) to routine laboratory practice. Design Early morning serum cortisol, salivary cortisol and cortisone were measured on fasting samples, and salivary hormones were measured in samples collected every 2 hours during waking hours, and 30 minutes after waking the following morning. Participants 43 healthy paediatric volunteers (19 female), median age 11.5 years, range 6.2 – 18.7, participated. Results Early morning serum cortisol (265nmol/L, 156 – 516) correlated strongly with salivary cortisol (4.7nmol/L, 1.1‐14.6) and cortisone (28.8nmol/L, 11.7‐56.6), p<0.0001 for both. Serum cortisol, salivary cortisol and salivary cortisone correlated directly with age (p<0.0001, p=0.002 and p=0.015 respectively), and salivary cortisone / cortisol ratio correlated indirectly with age (p=0.007). Between 08.00 and 21.00, area under the curve for salivary cortisol (mean ± 1 SD) was 41.8 ± 19.1 and for cortisone, 213.0 ± 61.2. Salivary cortisol was undetectable in 25/130 (19%) of samples collected after 13.00 while cortisone was always detectable. Discussion Salivary cortisol and cortisone concentrations are strongly related to serum cortisol concentrations, however cortisone may be a preferable measure as cortisol is often undetectable. Age may be an important factor in the interpretation of early morning cortisol measurements made in serum and saliva

The Emergence of Radiation from Gravitational Potential Wells: The Absence of ωM\omega M Effects

We consider a source of gravitational waves of frequency $\omega$, located near the center of a massive galaxy of mass $M$ and radius $R$, with $\omega\gg R^{-1}$. In the case of a perfect fluid galaxy, and of odd-parity waves, there is no direct matter-wave interaction and the propagation of the waves is affected by the galaxy only through the curvature of the spacetime background through which the waves propagate. We find that, in addition to the expected redshift of the radiation emerging from the galaxy, there is a small amount of backscatter, of order $M/\omega^2R^3$. We show that there is no suppression of radiative power by the factor $1+\omega^2M^2/4$ as has been recently predicted by Kundu. The origin of Kundu's suppression lies in the interpretation of a term in the expansion of the exterior field of the galaxy in inverse powers of radius. It is shown why that term is not related to the source strength or to the strength of the emerging radiation.Comment: 29p