Using online blogs to explore positive outcomes after burn injuries

This study uses blog analysis, a new and novel technique, to explore the positive outcomes experienced by burn survivors. This study examined 10 burn survivor blogs to offer a unique, longitudinal insight into burn survivor recovery. Using thematic analysis, three themes emerged: shift in self-perception, enhanced relationships and a change in life outlook. Many of these themes contained stories and experiences unique to a traumatic burn injury, suggesting that standardised trauma scales are not effectively measuring the impact of a burn in this population. Reflections on blog analysis are discussed, along with a recommendation that health researchers utilise the vast amount of data available from online blogs

A prospective study to assess the value of MMP-9 in improving the appropriateness of urgent referrals for colorectal cancer

Background Bowel cancer is common and is a major cause of death. Most people with bowel symptoms who meet the criteria for urgent referral to secondary care will not be found to have bowel cancer, and some people who are found to have cancer will have been referred routinely rather than urgently. If general practitioners could better identify people who were likely to have bowel cancer or conditions that may lead to bowel cancer, the pressure on hospital clinics may be reduced, enabling these patients to be seen more quickly. Increased levels of an enzyme called matrix metalloproteinase 9 (MMP-9) have been found to be associated with such conditions, and this can be measured from a blood sample. This study aims to find out whether measuring MMP-9 levels could improve the appropriateness of urgent referrals for patients with bowel symptoms. Methods People aged 18 years or older referred to a colorectal clinic will be asked to complete a questionnaire about symptoms, recent injuries or chronic illnesses (these can increase the level of matrix metalloproteinases) and family history of bowel cancer. A blood sample will be taken from people who consent to take part to assess MMP-9 levels, and the results of examination at the clinic and/or investigations arising from the clinic visit will be collected from hospital records. The accuracy of MMP-9 will be assessed by comparing the MMP-9 level with the resulting diagnosis. The combination of factors (e.g. symptoms and MMP-9 level) that best predict a diagnosis of malignancy (invasive disease or polyps) will be determined. Discussion Although guidelines are in place to facilitate referrals to colorectal clinics, symptoms alone do not adequately distinguish people with malignancy from people with benign conditions. This study will establish whether MMP-9 could assist this process. If this were the case, measurement of MMP-9 levels could be used by general practitioners to assist in the identification of people who were most likely to have bowel cancer or conditions that may lead to bowel cancer, and who should, therefore, be referred most urgently to secondary car

Reflections on a 'virtual' practice development unit: changing practice through identity development

Aims. This paper draws together the personal thoughts and critical reflections of key people involved in the establishment of a ‘virtual’ practice development unit of clinical nurse specialists in the south of England. Background. This practice development unit is ‘virtual’ in that it is not constrained by physical or specialty boundaries. It became the first group of Trust-wide clinical nurse specialists to be accredited in the UK as a practice development unit in 2004. Design and methods. The local university was asked to facilitate the accreditation process via 11 two-hour audio-recorded learning sessions. Critical reflections from practice development unit members, leaders and university staff were written 12 months after successful accreditation, and the framework of their content analysed. Findings and discussion. Practice development was seen as a way for the clinical nurse specialists to realize their potential for improving patient care by transforming care practice in a collaborative, interprofessional and evolutionary manner. The practice development unit provided a means for these nurses to analyse their role and function within the Trust. Roberts’ identity development model for nursing serves as a useful theoretical underpinning for the reflections contained in this paper. Conclusions. These narratives provide another example of nurses making the effort to shape and contribute to patient care through organizational redesign. This group of nurses began to realize that the structure of the practice development unit process provided them with the means to analyse their role and function within the organization and, as they reflected on this structure, their behaviour began to change. Relevance to clinical practice. Evidence from these reflections supports the view that practice development unit participants have secured a positive and professional identity and are, therefore, better able to improve the patient experience

Longitudinal assessment of neuronal 3D genomes in mouse prefrontal cortex

Neuronal epigenomes, including chromosomal loopings moving distal cis-regulatory elements into proximity of target genes, could serve as molecular proxy linking present-day-behaviour to past exposures. However, longitudinal assessment of chromatin state is challenging, because conventional chromosome conformation capture assays essentially provide single snapshots at a given time point, thus reflecting genome organization at the time of brain harvest and therefore are non-informative about the past. Here we introduce ‘NeuroDam’ to assess epigenome status retrospectively. Short-term expression of the bacterial DNA adenine methyltransferase Dam, tethered to the Gad1 gene promoter in mouse prefrontal cortex neurons, results in stable G[superscriptmethyl]ATC tags at Gad1-bound chromosomal contacts. We show by NeuroDam that mice with defective cognition 4 months after pharmacological NMDA receptor blockade already were affected by disrupted chromosomal conformations shortly after drug exposure. Retrospective profiling of neuronal epigenomes is likely to illuminate epigenetic determinants of normal and diseased brain development in longitudinal context.United States. National Institutes of Healt

Establishing a colorectal cancer research database from routinely collected health data: the process and potential from a pilot study.

OBJECTIVE: Colorectal cancer is a common cause of death and morbidity. A significant amount of data are routinely collected during patient treatment, but they are not generally available for research. The National Institute for Health Research Health Informatics Collaborative in the UK is developing infrastructure to enable routinely collected data to be used for collaborative, cross-centre research. This paper presents an overview of the process for collating colorectal cancer data and explores the potential of using this data source. METHODS: Clinical data were collected from three pilot Trusts, standardised and collated. Not all data were collected in a readily extractable format for research. Natural language processing (NLP) was used to extract relevant information from pseudonymised imaging and histopathology reports. Combining data from many sources allowed reconstruction of longitudinal histories for each patient that could be presented graphically. RESULTS: Three pilot Trusts submitted data, covering 12 903 patients with a diagnosis of colorectal cancer since 2012, with NLP implemented for 4150 patients. Timelines showing individual patient longitudinal history can be grouped into common treatment patterns, visually presenting clusters and outliers for analysis. Difficulties and gaps in data sources have been identified and addressed. DISCUSSION: Algorithms for analysing routinely collected data from a wide range of sites and sources have been developed and refined to provide a rich data set that will be used to better understand the natural history, treatment variation and optimal management of colorectal cancer. CONCLUSION: The data set has great potential to facilitate research into colorectal cancer

Shock Ignition Laser-Plasma Interactions in Ignition-Scale Plasmas

We use a subignition scale laser, the 30 kJ Omega, and a novel shallow-cone target to study laser-plasma interactions at the ablation-plasma density scale lengths and laser intensities anticipated for direct drive shock-ignition implosions at National Ignition Facility scale. Our results show that, under these conditions, the dominant instability is convective stimulated Raman scatter with experimental evidence of two plasmon decay (TPD) only when the density scale length is reduced. Particle-in-cell simulations indicate this is due to TPD being shifted to lower densities, removing the experimental back-scatter signature and reducing the hot-electron temperature. The experimental laser energy-coupling to hot electrons was found to be 1%-2.5%, with electron temperatures between 35 and 45 keV. Radiation-hydrodynamics simulations employing these hot-electron characteristics indicate that they should not preheat the fuel in MJ-scale shock ignition experiments

Novel animal models for studying complex brain disorders: BAC-driven miRNA-mediated in vivo silencing of gene expression

In schizophrenia, glutamic acid decarboxylase 1 (GAD1) disturbances are robust, consistently observed, cell-type specific and represent a core feature of the disease. In addition, neuropeptide Y (NPY), which is a phenotypic marker of a sub-population of GAD1-containing interneurons, has shown reduced expression in the prefrontal cortex in subjects with schizophrenia, suggesting that dysfunction of the NPY+ cortical interneuronal sub-population might be a core feature of this devastating disorder. However, modeling gene expression disturbances in schizophrenia in a cell type-specific manner has been extremely challenging. To more closely mimic these molecular and cellular human post-mortem findings, we generated a transgenic mouse in which we downregulated GAD1 mRNA expression specifically in NPY+ neurons. This novel, cell type-specific in vivo system for reducing gene expression uses a bacterial artificial chromosome (BAC) containing the NPY promoter-enhancer elements, the reporter molecule (eGFP) and a modified intron containing a synthetic microRNA (miRNA) targeted to GAD1. The animals of isogenic strains are generated rapidly, providing a new tool for better understanding the molecular disturbances in the GABAergic system observed in complex neuropsychiatric disorders such as schizophrenia. In the future, because of the small size of the silencing miRNAs combined with our BAC strategy, this method may be modified to allow generation of mice with simultaneous silencing of multiple genes in the same cells with a single construct, and production of splice-variant-specific knockdown animals

Transcriptome of iPSC-derived neuronal cells reveals a module of co-expressed genes consistently associated with autism spectrum disorder

Evaluation of expression profile in autism spectrum disorder (ASD) patients is an important approach to understand possible similar functional consequences that may underlie disease pathophysiology regardless of its genetic heterogeneity. Induced pluripotent stem cell (iPSC)-derived neuronal models have been useful to explore this question, but larger cohorts and different ASD endophenotypes still need to be investigated. Moreover, whether changes seen in this in vitro model reflect previous findings in ASD postmortem brains and how consistent they are across the studies remain underexplored questions. We examined the transcriptome of iPSC-derived neuronal cells from a normocephalic ASD cohort composed mostly of high-functioning individuals and from non-ASD individuals. ASD patients presented expression dysregulation of a module of co-expressed genes involved in protein synthesis in neuronal progenitor cells (NPC), and a module of genes related to synapse/neurotransmission and a module related to translation in neurons. Proteomic analysis in NPC revealed potential molecular links between the modules dysregulated in NPC and in neurons. Remarkably, the comparison of our results to a series of transcriptome studies revealed that the module related to synapse has been consistently found as upregulated in iPSC-derived neurons-which has an expression profile more closely related to fetal brain-while downregulated in postmortem brain tissue, indicating a reliable association of this network to the disease and suggesting that its dysregulation might occur in different directions across development in ASD individuals. Therefore, the expression pattern of this network might be used as biomarker for ASD and should be experimentally explored as a therapeutic target