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"Harvey, Kate"
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Squeak!
A mouse wakes up with a squeak, and his noise sets off a chain reaction of animals waking each other up.
Book
Family Mealtimes: A Systematic Umbrella Review of Characteristics, Correlates, Outcomes and Interventions
Systematic reviews have examined the multitude of studies investigating family mealtimes and their importance to child/adolescent health and psychosocial outcomes, but the focus of each is limited to specific aspects of family meals (e.g., frequency) and/or specific outcomes (e.g., nutrition). Their findings require synthesis and so a systematic umbrella review was undertaken. Databases were searched to identify systematic reviews (with or without meta-analysis/meta-synthesis) addressing at least one of the following questions: what are the characteristics and/or correlates of family mealtimes; what outcomes are associated with family mealtimes; are interventions aimed at promoting family mealtimes effective? Forty-one eligible reviews were retrieved. Their findings demonstrate that families with children/adolescents typically eat together at least a few days each week. More frequent family meals are predicted by a more positive mealtime environment, more positive attitudes towards family meals, the presence of younger children, and families having more time. Greater family meal frequency protects children/adolescents against a poorer diet, obesity, risk behaviours, poorer mental health and wellbeing, and poorer academic outcomes. Findings from interventions seeking to promote family mealtimes are mixed. This umbrella review provides a comprehensive and integrated understanding of research into family mealtimes, establishing where evidence is sound and where further research is needed.
Journal Article
Little Wolf's first howling
Little Wolf can hardly wait. Tonight he will howl at the moon to the top of the sky. First, Big Wolf demonstrates traditional howling form: AAAAAAAAAAOOOOOooooooooo. Then it's Little Wolf's turn. He's sure he is ready, but when the big moment comes, something happens. Something unexpected, something wild, something unbe-beep-bop-believable! Sisters Laura McGee Kvasnosky and Kate McGee have created a wonderful story about the importance of doing things your own way and being true to your heart when it swells with wildness and joy--Provided by publisher.
Book
What do parents perceive are the barriers and facilitators to accessing psychological treatment for mental health problems in children and adolescents? A systematic review of qualitative and quantitative studies
A minority of children and adolescents with mental health problems access treatment. The reasons for poor rates of treatment access are not well understood. As parents are a key gatekeeper to treatment access, it is important to establish parents’ views of barriers/facilitators to accessing treatment. The aims of this study are to synthesise findings from qualitative and quantitative studies that report parents’ perceptions of barriers/facilitators to accessing treatment for mental health problems in children/adolescents. A systematic review and narrative synthesis were conducted. Forty-four studies were included in the review and were assessed in detail. Parental perceived barriers/facilitators relating to (1) systemic/structural issues; (2) views and attitudes towards services and treatment; (3) knowledge and understanding of mental health problems and the help-seeking process; and (4) family circumstances were identified. Findings highlight avenues for improving access to child mental health services, including increased provision that is free to service users and flexible to their needs, with opportunities to develop trusting, supportive relationships with professionals. Furthermore, interventions are required to improve parents’ identification of mental health problems, reduce stigma for parents, and increase awareness of how to access services.
Journal Article
Targeting stromal remodeling and cancer stem cell plasticity overcomes chemoresistance in triple negative breast cancer
The cellular and molecular basis of stromal cell recruitment, activation and crosstalk in carcinomas is poorly understood, limiting the development of targeted anti-stromal therapies. In mouse models of triple negative breast cancer (TNBC), Hedgehog ligand produced by neoplastic cells reprograms cancer-associated fibroblasts (CAFs) to provide a supportive niche for the acquisition of a chemo-resistant, cancer stem cell (CSC) phenotype via FGF5 expression and production of fibrillar collagen. Stromal treatment of patient-derived xenografts with smoothened inhibitors (SMOi) downregulates CSC markers expression and sensitizes tumors to docetaxel, leading to markedly improved survival and reduced metastatic burden. In the phase I clinical trial EDALINE, 3 of 12 patients with metastatic TNBC derived clinical benefit from combination therapy with the SMOi Sonidegib and docetaxel chemotherapy, with one patient experiencing a complete response. These studies identify Hedgehog signaling to CAFs as a novel mediator of CSC plasticity and an exciting new therapeutic target in TNBC.
Stromal cell recruitment, activation and crosstalk with cancer cells is poorly understood. Here, the authors demonstrate that cancer cell-derived Hedgehog ligand triggers stromal remodeling that in turn induces a cancer-stem-cell like, drug-resistant phenotype of nearby cancer cells while treatment with smoothened inhibitors reverses these phenotypes.
Journal Article
Parent perceived barriers and facilitators of children’s adventurous play in Britain: a framework analysis
Background
From a public health perspective there is growing interest in children’s play, including play involving risk and adventure, in relation to children’s physical and mental health. Regarding mental health, it is theorised that adventurous play, where children experience thrilling, exciting emotions, offers important learning opportunities that prepare children for dealing with uncertainty and help prevent anxiety. Despite these benefits, adventurous play has decreased substantially within a generation. Parents have a key role in facilitating or limiting children’s opportunities for adventurous play, but research identifying the barriers and facilitators parents perceive in relation to adventurous play is scarce. The present study therefore examined the barriers to and facilitators of adventurous play as perceived by parents of school-aged children in Britain.
Methods
This study analysed data from a subsample of parents in Britain (
n
= 377) who participated in the nationally representative British Children’s Play Survey. Parents responded to two open-ended questions pertaining to the barriers to and facilitators of children’s adventurous play. Responses were analysed using a qualitative Framework Analysis, an approach suitable for managing large datasets with specific research questions.
Results
Four framework categories were identified: Social Environment; Physical Environment; Risk of Injury; Child Factors. Social Environment included barriers and facilitators related to parents, family and peers, as well as community and society. Dominant themes within the Social Environment related to perceptions about the certainty of child safety, such as supervision and the safety of society. Beliefs about the benefits of adventurous play for development and well-being were also important in the Social Environment. Physical Environment factors focused on safety and practical issues. Risk of Injury captured concerns about children being injured during play. Child Factors included child attributes, such as play preference, developmental ability and trait-like characteristics.
Conclusions
Improved understanding of what influences parent perceptions of adventurous play can inform public health interventions designed to improve children’s opportunities for and engagement in adventurous play, with a view to promote children’s physical and mental health.
Journal Article
Marine Structure Derived Calcium Phosphate–Polymer Biocomposites for Local Antibiotic Delivery
Hydrothermally converted coralline hydroxyapatite (HAp) particles loaded with medically active substances were used to develop polylactic acid (PLA) thin film composites for slow drug delivery systems. The effects of HAp particles within PLA matrix on the gentamicin (GM) release and release kinetics were studied. The gentamicin release kinetics seemed to follow Power law Korsmeyer Peppas model with mainly diffusional process with a number of different drug transport mechanisms. Statistical analysis shows very significant difference on the release of gentamicin between GM containing PLA (PLAGM) and GM containing HAp microspheres within PLA matrix (PLAHApGM) devices, which PLAHApGM displays lower release rates. The use of HAp particles improved drug stabilization and higher drug encapsulation efficiency of the carrier. HAp is also the source of Ca2+ for the regeneration and repair of diseased bone tissue. The release profiles, exhibited a steady state release rate with significant antimicrobial activity against Staphylococcus aureus (S. aureus) (SH1000) even at high concentration of bacteria. The devices also indicated significant ability to control the growth of bacterial even after four weeks of drug release. Clinical release profiles can be easily tuned from drug-HAp physicochemical interactions and degradation kinetics of polymer matrix. The developed systems could be applied to prevent microbial adhesion to medical implant surfaces and to treat infections mainly caused by S. aureus in surgery.
Journal Article
Deep whole genome sequencing identifies recurrent genomic alterations in commonly used breast cancer cell lines and patient-derived xenograft models
Background
Breast cancer cell lines (BCCLs) and patient-derived xenografts (PDXs) are the most frequently used models in breast cancer research. Despite their widespread usage, genome sequencing of these models is incomplete, with previous studies only focusing on targeted gene panels, whole exome or shallow whole genome sequencing. Deep whole genome sequencing is the most sensitive and accurate method to detect single nucleotide variants and indels, gene copy number and structural events such as gene fusions.
Results
Here we describe deep whole genome sequencing (WGS) of commonly used BCCL and PDX models using the Illumina X10 platform with an average ~ 60 × coverage. We identify novel genomic alterations, including point mutations and genomic rearrangements at base-pair resolution, compared to previously available sequencing data. Through integrative analysis with publicly available functional screening data, we annotate new genomic features likely to be of biological significance.
CSMD1
, previously identified as a tumor suppressor gene in various cancer types, including head and neck, lung and breast cancers, has been identified with deletion in 50% of our PDX models, suggesting an important role in aggressive breast cancers.
Conclusions
Our WGS data provides a comprehensive genome sequencing resource of these models.
Journal Article
A quantitative mass spectrometry-based approach to monitor the dynamics of endogenous chromatin-associated protein complexes
Understanding the dynamics of endogenous protein–protein interactions in complex networks is pivotal in deciphering disease mechanisms. To enable the in-depth analysis of protein interactions in chromatin-associated protein complexes, we have previously developed a method termed RIME (Rapid Immunoprecipitation Mass spectrometry of Endogenous proteins). Here, we present a quantitative multiplexed method (qPLEX-RIME), which integrates RIME with isobaric labelling and tribrid mass spectrometry for the study of protein interactome dynamics in a quantitative fashion with increased sensitivity. Using the qPLEX-RIME method, we delineate the temporal changes of the Estrogen Receptor alpha (ERα) interactome in breast cancer cells treated with 4-hydroxytamoxifen. Furthermore, we identify endogenous ERα-associated proteins in human Patient-Derived Xenograft tumours and in primary human breast cancer clinical tissue. Our results demonstrate that the combination of RIME with isobaric labelling offers a powerful tool for the in-depth and quantitative characterisation of protein interactome dynamics, which is applicable to clinical samples.
Chromatin-associated protein complexes play a critical role in the regulation of gene expression in health and disease. Here, the authors describe a sensitive mass spectrometry-based method to monitor the dynamic interactions of endogenous chromatin-associated protein complexes in clinical samples.
Journal Article