30 research outputs found

    Child protection and out-of-home placement experiences of preschool children born to mothers enrolled in methadone maintenance treatment during pregnancy

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    Children born to opiate-dependent women engaged in methadone maintenance treatment are at high risk of child welfare concern. However, few studies have examined the early child protection service (CPS) contacts of this group or the risk factors that place some but not other mother-infant dyads at increased risk of serious concern resulting in the removal of the child from the family home. As part of a prospective longitudinal study based in New Zealand, 73 women enrolled in methadone maintenance treatment during pregnancy and 54 non-methadone maintained comparison mothers were recruited during pregnancy and interviewed close to delivery, 18-months and 4.5-years. At each follow-up evaluation, detailed life history methods were used to describe children's family circumstances and all CPS contacts. By 4.5-years postdelivery, methadone maintained mothers were ten-times more likely to have been investigated by child protection services than comparison mothers (59% v. 6%, p<.001). Of these contacts, almost half (44%) resulted in the removal of the child from the family home compared to no comparison children (p<.001). These children were most frequently placed before age 1, with an average of 1-2 caregiver changes (range: 0-7). In addition to maternal methadone maintenance treatment during pregnancy (p<.001), significant independent predictors of child out-of-home placement included maternal depression (p=.01), maternal history of child custody loss (p=.02), and to some extent, high levels of family socioeconomic adversity (p=.06). Findings highlight the complex psychosocial needs of this high-risk group, as well as the need for careful monitoring and parenting support following hospital discharge.</p

    Stage 1 Registered Report: The relationship between handedness and language ability in children [version 1; referees: 2 approved]

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    Weak or inconsistent hand preference may be a risk factor for developmental language delay.  This study will test the extent to which variations in language skills are associated with the strength of hand preference. Data are drawn from a large sample (n = 569) of 6- to 7-year-old children unselected for ability, assessed at two time points, 6 months apart. Hand preference is assessed using the Quantitative Hand Preference task (QHP) and five uni-manual motor tasks. Language skills (expressive and receptive vocabulary, receptive grammar, and morphological awareness) are assessed with standardized measures. If weak cerebral lateralisation (as assessed by the QHP task) is a risk factor for language difficulties, it should be possible to detect such effects in the large representative sample of children examined here

    Low but contrasting neutral genetic differentiation shaped by winter temperature in European great tits

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    Gene flow is usually thought to reduce genetic divergence and impede local adaptation by homogenising gene pools between populations. However, evidence for local adaptation and phenotypic differentiation in highly mobile species, experiencing high levels of gene flow, is emerging. Assessing population genetic structure at different spatial scales is thus a crucial step towards understanding mechanisms underlying intraspecific differentiation and diversification. Here, we studied the population genetic structure of a highly mobile species – the great tit Parus major – at different spatial scales. We analysed 884 individuals from 30 sites across Europe including 10 close-by sites (< 50 km), using 22 microsatellite markers. Overall we found a low but significant genetic differentiation among sites (FST = 0.008). Genetic differentiation was higher, and genetic diversity lower, in south-western Europe. These regional differences were statistically best explained by winter temperature. Overall, our results suggest that great tits form a single patchy metapopulation across Europe, in which genetic differentiation is independent of geographical distance and gene flow may be regulated by environmental factors via movements related to winter severity. This might have important implications for the evolutionary trajectories of sub-populations, especially in the context of climate change, and calls for future investigations of local differences in costs and benefits of philopatry at large scales

    Cell-free DNA profiling of metastatic prostate cancer reveals microsatellite instability, structural rearrangements and clonal hematopoiesis.

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    This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.BACKGROUND: There are multiple existing and emerging therapeutic avenues for metastatic prostate cancer, with a common denominator, which is the need for predictive biomarkers. Circulating tumor DNA (ctDNA) has the potential to cost-efficiently accelerate precision medicine trials to improve clinical efficacy and diminish costs and toxicity. However, comprehensive ctDNA profiling in metastatic prostate cancer to date has been limited. METHODS: A combination of targeted and low-pass whole genome sequencing was performed on plasma cell-free DNA and matched white blood cell germline DNA in 364 blood samples from 217 metastatic prostate cancer patients. RESULTS: ctDNA was detected in 85.9% of baseline samples, correlated to line of therapy and was mirrored by circulating tumor cell enumeration of synchronous blood samples. Comprehensive profiling of the androgen receptor (AR) revealed a continuous increase in the fraction of patients with intra-AR structural variation, from 15.4% during first-line metastatic castration-resistant prostate cancer therapy to 45.2% in fourth line, indicating a continuous evolution of AR during the course of the disease. Patients displayed frequent alterations in DNA repair deficiency genes (18.0%). Additionally, the microsatellite instability phenotype was identified in 3.81% of eligible samples (≥ 0.1 ctDNA fraction). Sequencing of non-repetitive intronic and exonic regions of PTEN, RB1, and TP53 detected biallelic inactivation in 47.5%, 20.3%, and 44.1% of samples with ≥ 0.2 ctDNA fraction, respectively. Only one patient carried a clonal high-impact variant without a detectable second hit. Intronic high-impact structural variation was twice as common as exonic mutations in PTEN and RB1. Finally, 14.6% of patients presented false positive variants due to clonal hematopoiesis, commonly ignored in commercially available assays. CONCLUSIONS: ctDNA profiles appear to mirror the genomic landscape of metastatic prostate cancer tissue and may cost-efficiently provide somatic information in clinical trials designed to identify predictive biomarkers. However, intronic sequencing of the interrogated tumor suppressors challenges the ubiquitous focus on coding regions and is vital, together with profiling of synchronous white blood cells, to minimize erroneous assignments which in turn may confound results and impede true associations in clinical trials.The Belgian Foundation Against Cancer (grant number C/2014/227); Kom op tegen Kanker (Stand up to Cancer), the Flemish Cancer Society (grant number 00000000116000000206); Royal College of Surgeons/Cancer Research UK (C19198/A1533); The Cancer Research Funds of Radiumhemmet, through the PCM program at KI (grant number 163012); The Erling-Persson family foundation (grant number 4-2689-2016); the Swedish Research Council (grant number K2010-70X-20430-04-3), and the Swedish Cancer Foundation (grant number 09-0677)

    Avoiding the potential pitfalls of using negative priming tasks in developmental studies: Assessing inhibitory control in children, adolescents, and adults.

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    Despite being ignored, visual distractors often produce traceable negative priming (NP) effects that can be used to investigate inhibitory processes. Robust NP effects are typically found with young adults, but not with children. Using 2 different NP tasks, the authors compared NP in 5 different age groups spanning 5 to 25 years of age. The 1st task revealed comparable NP between all age groups, but a linear decrease in NP through childhood to early adulthood. In the 2nd task, NP decreased linearly into adulthood, with children actually showing larger NP than adults. This Age Group Ă— NP interaction was eliminated, however, when reaction time data were log transformed to control for age differences in overall processing speed. When appropriately transformed data were used, both experiments showed that NP was intact and comparable between children, adolescents, and adults, and suggested that an inhibitory process is fully developed by early childhood. The results highlight how potential pitfalls might be avoided when comparing NP in children and adults.</p

    Preschool executive control on the Shape School task: Measurement considerations and utility.

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    Executive functions (EF) necessary for purposeful goal-directed activities undergo rapid change and development during the preschool years. However, of the few psychometrically valid measures of EF suitable for use with preschoolers, information on task sensitivity and predictive validity is scant. The neurodevelopmental correlates of early executive difficulties are also largely unknown. In this study, the discriminant and predictive validity of the recently developed Shape School task (Espy, Bull, Martin, &amp; Stroup, 2006) was examined with data from a regional sample of 209 preschool children at age 4 years. A 2-tiered measurement approach was used, with task completion examined in addition to efficiency. Children's performance was also examined in relation to functioning in a range of neurodevelopmental domains. The Shape School task showed some usefulness in capturing expected differences between at-risk and typically developing children. Performance loaded heavily on language and global cognitive abilities. However, several other factors were also implicated, including attention, motor skills, and ocular control. In addition, task completion and efficiency scores appeared to reflect different aspects of performance, and their associations with neurodevelopmental function and later academic achievement on the Woodcock-Johnson Tests of Achievement at age 6 years also differed. Implications for the application of the Shape School task are discussed.</p

    A comparison of parent and staff perceptions of setting-specific and everyday stressors encountered by parents with very preterm infants experiencing neonatal intensive care

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    Background: Stress responses among parents of premature infants experiencing the neonatal intensive care unit (NICU) environment are widely reported. However, less is known about how nurses perceive parents' experiences or how stressors relating to demands on family finances and practical challenges associated with infant hospitalization contribute to parental stress levels in the NICU. Objective: 1) To compare parent and staff perceptions of the stressors facing parents experiencing neonatal intensive care; and 2) to develop a scale suitable for identifying stressors outside the NICU setting. Methods: At infant 34. weeks, parents (n=. 21) of very preterm infants (≤. 32. weeks GA) and NICU nurses (n=. 23) completed the Parental Stressor Scale: NICU (PSS: NICU) and a custom-made External Stressor Scale (ESS: NICU). Results: Nurses perceived parents to experience higher stress in the NICU than parents themselves (ps. Conclusions: Periodic reassessments of staff and parent perceptions should be encouraged along with research dedicated to a fuller understanding of the range of stressors facing parents experiencing neonatal intensive care in attempts to reduce stress levels and aid integration into the unit.</p
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