Long-term collateral effects of parent programs on child maltreatment proxies:Can administrative data provide useful insights?

Collecting child maltreatment data from participants is expensive and time-consuming, and often suffers from substantial attrition rates. Administrative population data may prove fruitful to overcome these barriers. The aim of this study was twofold: (1) to illustrate how administrative data may be used in evaluating long-term intervention effects; and (2) to examine collateral effects of three preventive early childhood interventions offered to families in the Netherlands (Supportive Parenting, VoorZorg, and Incredible Years). Using population data, four proxies of child maltreatment were assessed to examine collateral intervention effects: incidences of child protection orders, placements of children in residential care, crime victimization of children or their parents, and parental registrations as a crime suspect. The results revealed no significant differences between experimental and control conditions on any of these proxies, with very small effect sizes (ranging from Cramer's V = 0.01 to Cramer's V = 0.10). We conclude that the results do not provide support for collateral effects, but that studying other outcomes may provide this support. We further discuss that small sample sizes and low prevalences challenge studies using administrative data. Notwithstanding these limitations, we conclude that administrative data can strengthen the evidence base for collateral and direct intervention effects.</p

In the Eye of the Beholder?

This study examined parent-observer discrepancies in assessments of negative child behavior and negative parenting behavior to shed more light on correlates with these discrepancies. Specifically, we hypothesized that informant discrepancy between observers and parents on child behavior would be larger when parents reported high levels of negative parenting (and vice versa) because high levels of these behaviors might be indicators of negative perceiver bias or patterns of family dysfunctioning. Using restricted correlated trait–models, we analyzed cross-sectional observation (coded with the Dyadic Parent-Child Interaction Coding System) and survey data (Eyberg Child Behavior Inventory and Parenting Practices Interview) of 386 Dutch parentchild dyads with children aged 4–8 years (Mage = 6.21, SD = 1.33; 55.30% boys). Small associations between parent-reported and observed child and parenting behavior were found, indicating high discrepancy. In line with our hypothesis, this discrepancy was higher when parents self-reported more negative parenting or more negative child behavior. Parent-observer discrepancy on negative child behavior was also predicted by child gender. For boys parents reported higher levels of negative child behavior than were observed, but for girls parents reported lower levels of negative child behavior than were observed. These findings suggest that informant discrepancies between observers and parents might provide important information on underlying, problematic family functioning and may help to identify those families most in need of help

Rational design of a conformation-specific antibody for the quantification of A beta oligomers

The accurate quantification of the amounts of small oligomeric assemblies formed by the amyloid β (Aβ) peptide represents a major challenge in the Alzheimer’s field. There is therefore great interest in the development of methods to specifically detect these oligomers by distinguishing them from larger aggregates. The availability of these methods will enable the development of effective diagnostic and therapeutic interventions for this and other diseases related to protein misfolding and aggregation. We describe here a single-domain antibody able to selectively quantify oligomers of the Aβ peptide in isolation and in complex protein mixtures from animal models of disease

Rational design of a conformation-specific antibody for the quantification of Aβ oligomers.

Protein misfolding and aggregation is the hallmark of numerous human disorders, including Alzheimer's disease. This process involves the formation of transient and heterogeneous soluble oligomers, some of which are highly cytotoxic. A major challenge for the development of effective diagnostic and therapeutic tools is thus the detection and quantification of these elusive oligomers. Here, to address this problem, we develop a two-step rational design method for the discovery of oligomer-specific antibodies. The first step consists of an "antigen scanning" phase in which an initial panel of antibodies is designed to bind different epitopes covering the entire sequence of a target protein. This procedure enables the determination through in vitro assays of the regions exposed in the oligomers but not in the fibrillar deposits. The second step involves an "epitope mining" phase, in which a second panel of antibodies is designed to specifically target the regions identified during the scanning step. We illustrate this method in the case of the amyloid β (Aβ) peptide, whose oligomers are associated with Alzheimer's disease. Our results show that this approach enables the accurate detection and quantification of Aβ oligomers in vitro, and in Caenorhabditis elegans and mouse hippocampal tissues

Pathways to Youth Behavior: The Role of Genetic, Neural, and Behavioral Markers

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142554/1/jora12341_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142554/2/jora12341.pd

Rationally Designed Antibodies as Research Tools to Study the Structure–Toxicity Relationship of Amyloid-β Oligomers

Alzheimer’s disease is associated with the aggregation of the amyloid-β peptide (Aβ), resulting in the deposition of amyloid plaques in brain tissue. Recent scrutiny of the mechanisms by which Aβ aggregates induce neuronal dysfunction has highlighted the importance of the Aβ oligomers of this protein fragment. Because of the transient and heterogeneous nature of these oligomers, however, it has been challenging to investigate the detailed mechanisms by which these species exert cytotoxicity. To address this problem, we demonstrate here the use of rationally designed single-domain antibodies (DesAbs) to characterize the structure−toxicity relationship of Aβ oligomers. For this purpose, we use Zn2+-stabilized oligomers of the 40-residue form of Aβ (Aβ40) as models of brain Aβ oligomers and two single-domain antibodies (DesAb18-24 and DesAb34-40), designed to bind to epitopes at residues 18−24 and 34−40 of Aβ40, respectively. We found that the DesAbs induce a change in structure of the Zn2+-stabilized Aβ40 oligomers, generating a simultaneous increase in their size and solvent-exposed hydrophobicity. We then observed that these increments in both the size and hydrophobicity of the oligomers neutralize each other in terms of their effects on cytotoxicity, as predicted by a recently proposed general structure−toxicity relationship, and observed experimentally. These results illustrate the use of the DesAbs as research tools to investigate the biophysical and cytotoxicity properties of Aβ oligomers

Rationally Designed Antibodies as Research Tools to Study the Structure–Toxicity Relationship of Amyloid-β Oligomers

Alzheimer’s disease is associated with the aggregation of the amyloid-β peptide (Aβ), resulting in the deposition of amyloid plaques in brain tissue. Recent scrutiny of the mechanisms by which Aβ aggregates induce neuronal dysfunction has highlighted the importance of the Aβ oligomers of this protein fragment. Because of the transient and heterogeneous nature of these oligomers, however, it has been challenging to investigate the detailed mechanisms by which these species exert cytotoxicity. To address this problem, we demonstrate here the use of rationally designed single-domain antibodies (DesAbs) to characterize the structure−toxicity relationship of Aβ oligomers. For this purpose, we use Zn2+-stabilized oligomers of the 40-residue form of Aβ (Aβ40) as models of brain Aβ oligomers and two single-domain antibodies (DesAb18-24 and DesAb34-40), designed to bind to epitopes at residues 18−24 and 34−40 of Aβ40, respectively. We found that the DesAbs induce a change in structure of the Zn2+-stabilized Aβ40 oligomers, generating a simultaneous increase in their size and solvent-exposed hydrophobicity. We then observed that these increments in both the size and hydrophobicity of the oligomers neutralize each other in terms of their effects on cytotoxicity, as predicted by a recently proposed general structure−toxicity relationship, and observed experimentally. These results illustrate the use of the DesAbs as research tools to investigate the biophysical and cytotoxicity properties of Aβ oligomers

Could scale-up of parenting programmes improve child disruptive behaviour and reduce social inequalities? Using individual participant data meta-analysis to establish for whom programmes are effective and cost-effective

Background Child disruptive behavioural problems are a large and costly public health problem. The Incredible Years® (IY) parenting programme has been disseminated across the UK to prevent this problem and shown to be effective in several trials. It is vital for policy to know for which families IY is most effective, to be sure that it helps reduce, rather than widen, socioeconomic inequalities. Individual trials lack power and generalisability to examine differential effects; conventional meta-analysis lacks information about within-trial variability in effects. Objectives To overcome these limitations by pooling individual-level data from the IY parenting trials in Europe to examine to what extent it benefits socially disadvantaged families. Secondary objectives examine (1) additional moderators of effects on child behaviour, (2) wider health benefits and potential harms and (3) costs, cost-effectiveness and potential long-term savings. Design Individual participant data meta-analysis of 14 randomised trials of the IY parenting intervention. Settings UK (eight trials), the Netherlands, Ireland, Norway, Sweden and Portugal. Participants Data were from 1799 families, with children aged 2–10 years (mean 5.1 years; 63% boys). Interventions IY Basic parenting programme. Main outcome measures Primary outcome was disruptive child behaviour, determined by the Eyberg Child Behavior Inventory Intensity scale (ECBI-I). Secondary outcomes included self-reported parenting practices, parenting stress, mental health, children’s attention deficit hyperactivity disorder (ADHD) and emotional symptoms. Results There were no differential effects of IY on disruptive behaviour in families with different levels of social/socioeconomic disadvantage or differential effects for ethnic minority families, families with different parenting styles, or for children with comorbid ADHD or emotional problems or of different ages. Some moderators were found: intervention effects were strongest in children with more severe baseline disruptive behaviour, in boys, and in children with parents who were more depressed. Wider health benefits included reduced child ADHD symptoms, greater parental use of praise, and reduced harsh and inconsistent discipline. The intervention did not improve parental depression, stress, self-efficacy or children’s emotional problems. Economic data were available for five UK and Ireland trials (maximum n = 608). The average cost per person of the IY intervention was £2414. The probability that the IY intervention is considered cost-effective is 99% at a willingness to pay of £145 per 1-point improvement on the ECBI-I. Estimated longer-term savings over 20 years range from £1000 to £8400 per child, probably offsetting the cost of the intervention. Limitations Limitations include a focus on one parenting programme; the need to make assumptions in harmonising data; and the fact that data addressed equalities in the effectiveness of, not access to, the intervention. Conclusions There is no evidence that the benefits of the IY parenting intervention are reduced in disadvantaged or minority families; benefits are greater in the most distressed families, including parents who are depressed. Thus, the intervention is unlikely to widen socioeconomic inequalities in disruptive behaviour and may have effects in narrowing inequalities due to parent depression. It was as likely to be effective for older as for younger children. It has wider benefits for ADHD and parenting and is likely to be considered to be cost-effective. Researchers/funders should encourage data sharing to test equity and other moderator questions for other interventions; further research is needed on enhancing equality of access to interventions