Extended Family Outreach in Hereditary Cancer Using Web-Based Genealogy, Direct-to-Consumer Ancestry Genetics, and Social Media: Mixed Methods Process Evaluation of the ConnectMyVariant Intervention.

Background: Cascade screening, defined as helping at-risk relatives get targeted genetic testing of familial variants for dominant hereditary cancer syndromes, is a proven component of cancer prevention; however, its uptake is low. We developed and conducted a pilot study of the ConnectMyVariant intervention, in which participants received support to contact at-risk relatives that extended beyond first-degree relatives and encourage relatives to obtain genetic testing and connect with others having the same variant through email and social media. The support that participants received included listening to participants' needs, assisting with documentary genealogy to find common ancestors, facilitating direct-to-consumer DNA testing and interpretation, and assisting with database searches.

DNA extraction from placental, fetal and neonatal tissue at autopsy: what organ to sample for DNA in the genomic era?

Incorporation of genome and exome sequencing into fetal and neonatal autopsy investigations has been shown to improve diagnostic yield. This requires deoxyribonucleic acid (DNA) to be extracted from either the placenta or autopsy tissue for molecular testing. However, the sources and quality of DNA obtained are highly variable and there are no adequate published data on what tissue is most ideal to sample for DNA extraction in this setting.

Applying the Criminal Narrative Experience Framework to Young Offenders.

The present study applied the Criminal Narrative Experience for the first time with young offenders ( N = 23). The analysis was based on young people serving a community sentence and attending a Youth Offending Team. Participants completed questionnaires relating to their roles and emotions during a typical offence and data were examined with Smallest Space Analysis (SSA) to identify if the themes were replicated.

Analgesic prescribing in palliative care.

Pain management requires a multimodal approach involving pharmacological and non-pharmacological strategies. It is important to take a detailed history and examine the patient before prescribing any analgesia. This article focuses on assessment and management of pain in palliative care patients.

Management of personal safety risk for lever operation in mechanical railway signal boxes.

Despite increased implementation of computer control systems in managing and regulating rail networks, mechanical signal boxes using lever operation will be in place for years to come. A rolling risk assessment programme identified a number of levers in mechanical signal boxes within the UK rail network which potentially presented unacceptable personal safety risk to signallers. These levers operate both points and signals and the risk is primarily the weights which have to be moved when pulling and pushing the levers.

Directed differentiation of human embryonic stem cells toward chondrocytes.

We report a chemically defined, efficient, scalable and reproducible protocol for differentiation of human embryonic stem cells (hESCs) toward chondrocytes. HESCs are directed through intermediate developmental stages using substrates of known matrix proteins and chemically defined media supplemented with exogenous growth factors. Gene expression analysis suggests that the hESCs progress through primitive streak or mesendoderm to mesoderm, before differentiating into a chondrocytic culture comprising cell aggregates.

Bone marrow-derived mesenchymal stem cells express the pericyte marker 3G5 in culture and show enhanced chondrogenesis in hypoxic conditions.

Bone marrow-derived mesenchymal stem cells are a potential source of cells for the repair of articular cartilage defects. Hypoxia has been shown to improve chondrogenesis in some cells. In this study, bone marrow-derived stem cells were characterized and the effects of hypoxia on chondrogenesis investigated.

The Operational Demand Evaluation Checklist (ODEC) of workload for railway signalling.

This paper is concerned with the interpretation and assessment of mental workload, and in particular assessment of the load imposed by the work system. It highlights a framework created to direct the development of workload assessment tools capable of assessing the dimensions most relevant to the population being studied, in our case railway signallers. A tool to capture the operational demands on the rail signaller was required to evaluate the load from the system they operated.

Hyperosmolarity regulates SOX9 mRNA posttranscriptionally in human articular chondrocytes.

The transcription factor SOX9 regulates cartilage extracellular matrix gene expression and is essential for chondrocyte differentiation. We previously showed that activation of p38 MAPK by cycloheximide in human chondrocytes leads to stabilization of SOX9 mRNA (Tew SR and Hardingham TE. J Biol Chem 281: 39471-39479, 2006).

Molecular dissection of integrin signalling proteins in the control of mammary epithelial development and differentiation.

Cell-matrix adhesion is essential for the development and tissue-specific functions of epithelia. For example, in the mammary gland, beta1-integrin is necessary for the normal development of alveoli and for the activation of endocrine signalling pathways that determine cellular differentiation. However, the adhesion complex proteins linking integrins with downstream effectors of hormonal signalling pathways are not known.

Ablation of beta1 integrin in mammary epithelium reveals a key role for integrin in glandular morphogenesis and differentiation.

Integrin-mediated adhesion regulates the development and function of a range of tissues; however, little is known about its role in glandular epithelium. To assess the contribution of beta1 integrin, we conditionally deleted its gene in luminal epithelia during different stages of mouse mammary gland development and in cultured primary mammary epithelia. Loss of beta1 integrin in vivo resulted in impaired alveologenesis and lactation.

Caspase-mediated Cleavage of Insulin Receptor Substrate.

Apoptosis is an important mechanism for maintaining tissue homeostasis. The efficient induction and execution of apoptosis are essential for cell clearance in specific developmental situations. Insulin-like growth factor (IGF)-I is a survival factor for epithelial cells in the mammary gland, and its withdrawal or inhibition leads to apoptosis.

A role for the cytoskeleton in prolactin-dependent mammary epithelial cell differentiation.

The function of exocrine glands depends on signals within the extracellular environment. In the mammary gland, integrin-mediated adhesion to the extracellular matrix protein laminin co-operates with soluble factors such as prolactin to regulate tissue-specific gene expression. The mechanism of matrix and prolactin crosstalk and the activation of downstream signals are not fully understood.

Cell-matrix interactions during development and apoptosis of the mouse mammary gland in vivo.

Epithelial cell survival is dependent on extracellular signals provided by both soluble factors and by adhesion. In the mammary gland, extensive apoptosis of epithelial cells occurs rapidly when lactation ceases, but the mechanism of apoptosis induction is not known. In tissue culture, mammary epithelial cells require laminin as a survival ligand and specific beta1 integrins are necessary to suppress apoptosis.