Reframing postconcussional syndrome as an interface disorder of neurology, psychiatry and psychology.

Persistent symptoms following a minor head injury can cause significant morbidity, yet the underlying mechanisms for this are poorly understood. The shortcomings of the current terminology that refer to non-specific symptom clusters is discussed. This update considers the need for a multi-dimensional approach for the heterogenous mechanisms driving persistent symptoms after mild traumatic brain injury. Relevant pathophysiology is discussed to make the case for mild traumatic brain injury to be conceptualised as an interface disorder spanning neurology, psychiatry and psychology. The relevance of pre-injury factors, psychological co-morbidities and their interaction with the injury to produce persistent symptoms are reviewed. The interplay with psychiatric diagnoses, functional and somatic symptom disorder presentations and the influence of the medicolegal process is considered. The judicious use and interpretation of investigations given the above complexity is discussed, with suggestions of how the explanation of the diagnostic formulation to the patient can be tailored, including insight into the above processes, to aid recovery. Moving beyond the one-dimensional concept of "postconcussional syndrome" and reframing the cause of persistent symptoms following mild traumatic brain injury in a bio-psycho-socio-ecological model will hopefully improve understanding of the underlying contributory mechanistic interactions and facilitate treatment

Exercise for people living with frailty and receiving haemodialysis:a mixed-methods randomised controlled feasibility study

Objectives Frailty is highly prevalent in haemodialysis (HD) patients, leading to poor outcomes. This study aimed to determine whether a randomised controlled trial (RCT) of intradialytic exercise is feasible for frail HD patients, and explore how the intervention may be tailored to their needs.Design Mixed-methods feasibility.Setting and participants Prevalent adult HD patients of the CYCLE-HD trial with a Clinical Frailty Scale Score of 4–7 (vulnerable to severely frail) were eligible for the feasibility study.Interventions Participants in the exercise group undertook 6 months of three times per week, progressive, moderate intensity intradialytic cycling (IDC).Outcomes Primary outcomes were related to feasibility. Secondary outcomes were falls incidence measured from baseline to 1 year following intervention completion, and exercise capacity, physical function, physical activity and patient-reported outcomes measured at baseline and 6 months. Acceptability of trial procedures and the intervention were explored via diaries and interviews with n=25 frail HD patients who both participated in (n=13, 52%), and declined (n=12, 48%), the trial.Results 124 (30%) patients were eligible, and of these 64 (52%) consented with 51 (80%) subsequently completing a baseline assessment. n=24 (71% male; 59±13 years) dialysed during shifts randomly assigned to exercise and n=27 (81% male; 65±11 years) shifts assigned to usual care. n=6 (12%) were lost to follow-up. The exercise group completed 74% of sessions. 27%–89% of secondary outcome data were missing. Frail HD patients outlined several ways to enhance trial procedures. Maintaining ability to undertake activities of daily living and social participation were outcomes of primary importance. Participants desired a varied exercise programme.Conclusions A definitive RCT is feasible, however a comprehensive exercise programme may be more efficacious than IDC in this population.</div

A randomised controlled trial of a brief online mindfulness-based intervention on paranoia in a non-clinical sample

Paranoia is common and distressing in the general population and can impact on health, emotional well-being and social functioning, such that effective interventions are needed. Brief online mindfulness-based interventions (MBIs) have been shown to reduce symptoms of anxiety and depression in non-clinical samples, however at present there is no research investigating whether they can reduce paranoia. The current study explored whether a brief online MBI increased levels of mindfulness and reduced levels of paranoia in a non-clinical population. The mediating effect of mindfulness on any changes in paranoia was also investigated. One hundred and ten participants were randomly allocated to either a two week online MBI including 10 minutes of daily guided mindfulness practice or to a waitlist control condition. Measures of mindfulness and paranoia were administered at baseline, post-intervention and one-week follow-up. Participants in the MBI group displayed significantly greater reductions in paranoia compared to the waitlist control group. Mediation analysis demonstrated that change in mindfulness skills (specifically the observe, describe and nonreact facets of the FFMQ) mediated the relationship between intervention type and change in levels of paranoia. This study provides evidence that a brief online MBI can significantly reduce levels of paranoia in a non-clinical population. Furthermore, increases in mindfulness skills from this brief online MBI can mediate reductions in non-clinical paranoia. The limitations of the study are discussed

The Impact of Falls: A Qualitative Study of the Experiences of People Receiving Haemodialysis

The prevalence of falls is high in people receiving haemodialysis (HD). This study aimed to explore the experiences of people receiving HD who had fallen in the last six months. A qualitative study, informed by constructivist grounded theory, used semi-structured interviews in combination with falls diaries. Twenty-five adults (mean age of 69 ± 10 years, 13 female, 13 White British) receiving HD with a history of at least one fall in the last six months (median 3, IQR 2−4) participated. Data were organised within three themes: (a) participants’ perceptions of the cause of their fall(s): poor balance, weakness, and dizziness, exacerbated by environmental causes, (b) the consequences of the fall: injuries were disproportionate to the severity of the fall leading to loss of confidence, function and disruptions to HD, (c) reporting and coping with falls: most did not receive any specific care regarding falls. Those who attended falls services reported access barriers. In response, personal coping strategies included avoidance, vigilance, and resignation. These findings indicate that a greater focus on proactively identifying falls, comprehensive assessment, and timely access to appropriate falls prevention programmes is required to improve care and outcomes

Assessing the Impact and Effectiveness of Hearing Voices Network Self-Help Groups

The Hearing Voices Network (HVN) is an influential service-user led organisation that promotes self-help as an important aspect of recovery. This study presents the first systematic assessment of the impact and effectiveness of HVN self-help groups. A customized 45-item questionnaire, the Hearing Voices Groups Survey, was sent to 62 groups affiliated with the English HVN. 101 responses were received. Group attendance was credited with a range of positive emotional, social and clinical outcomes. Aspects that were particularly valued included: opportunities to meet other voice hearers, provision of support that was unavailable elsewhere, and the group being a safe and confidential place to discuss difficult issues. Participants perceived HVN groups to facilitate recovery processes and to be an important resource for helping them cope with their experiences. Mental health professionals can use their expertise to support the successful running of these groups

Gene Regulation and Epigenetic Remodeling in Murine Embryonic Stem Cells by c-Myc

BACKGROUND:The Myc oncoprotein, a transcriptional regulator involved in the etiology of many different tumor types, has been demonstrated to play an important role in the functions of embryonic stem (ES) cells. Nonetheless, it is still unclear as to whether Myc has unique target and functions in ES cells. METHODOLOGY/PRINCIPAL FINDINGS:To elucidate the role of c-Myc in murine ES cells, we mapped its genomic binding sites by chromatin-immunoprecipitation combined with DNA microarrays (ChIP-chip). In addition to previously identified targets we identified genes involved in pluripotency, early development, and chromatin modification/structure that are bound and regulated by c-Myc in murine ES cells. Myc also binds and regulates loci previously identified as Polycomb (PcG) targets, including genes that contain bivalent chromatin domains. To determine whether c-Myc influences the epigenetic state of Myc-bound genes, we assessed the patterns of trimethylation of histone H3-K4 and H3-K27 in mES cells containing normal, increased, and reduced levels of c-Myc. Our analysis reveals widespread and surprisingly diverse changes in repressive and activating histone methylation marks both proximal and distal to Myc binding sites. Furthermore, analysis of bulk chromatin from phenotypically normal c-myc null E7 embryos demonstrates a 70-80% decrease in H3-K4me3, with little change in H3-K27me3, compared to wild-type embryos indicating that Myc is required to maintain normal levels of histone methylation. CONCLUSIONS/SIGNIFICANCE:We show that Myc induces widespread and diverse changes in histone methylation in ES cells. We postulate that these changes are indirect effects of Myc mediated by its regulation of target genes involved in chromatin remodeling. We further show that a subset of PcG-bound genes with bivalent histone methylation patterns are bound and regulated in response to altered c-Myc levels. Our data indicate that in mES cells c-Myc binds, regulates, and influences the histone modification patterns of genes involved in chromatin remodeling, pluripotency, and differentiation

Notch Ankyrin Repeat Domain Variation Influences Leukemogenesis and Myc Transactivation

, cell-based and structural analyses to compare the abilities of activated Notch1-4 to support T cell development, induce T cell acute lymphoblastic leukemia/lymphoma (T-ALL), and maintain T-ALL cell growth and survival., a direct Notch target that has an important role in Notch-associated T-ALL.We conclude that the leukemogenic potentials of Notch receptors vary, and that this functional difference stems in part from divergence among the highly conserved ankyrin repeats, which influence the transactivation of specific target genes involved in leukemogenesis

Rapid spatiotemporal variations in rift structure during development of the Corinth Rift, central Greece

The Corinth Rift, central Greece, enables analysis of early rift development as it is young (<5Ma) and highly active and its full history is recorded at high resolution by sedimentary systems. A complete compilation of marine geophysical data, complemented by onshore data, is used to develop a high-resolution chronostratigraphy and detailed fault history for the offshore Corinth Rift, integrating interpretations and reconciling previous discrepancies. Rift migration and localization of deformation have been significant within the rift since inception. Over the last circa 2Myr the rift transitioned from a spatially complex rift to a uniform asymmetric rift, but this transition did not occur synchronously along strike. Isochore maps at circa 100kyr intervals illustrate a change in fault polarity within the short interval circa 620-340ka, characterized by progressive transfer of activity from major south dipping faults to north dipping faults and southward migration of discrete depocenters at ~30m/kyr. Since circa 340ka there has been localization and linkage of the dominant north dipping border fault system along the southern rift margin, demonstrated by lateral growth of discrete depocenters at ~40m/kyr. A single central depocenter formed by circa 130ka, indicating full fault linkage. These results indicate that rift localization is progressive (not instantaneous) and can be synchronous once a rift border fault system is established. This study illustrates that development processes within young rifts occur at 100kyr timescales, including rapid changes in rift symmetry and growth and linkage of major rift faults

Modelling of the effect of ELMs on fuel retention at the bulk W divertor of JET

Effect of ELMs on fuel retention at the bulk W target of JET ITER-Like Wall was studied with multi-scale calculations. Plasma input parameters were taken from ELMy H-mode plasma experiment. The energetic intra-ELM fuel particles get implanted and create near-surface defects up to depths of few tens of nm, which act as the main fuel trapping sites during ELMs. Clustering of implantation-induced vacancies were found to take place. The incoming flux of inter-ELM plasma particles increases the different filling levels of trapped fuel in defects. The temperature increase of the W target during the pulse increases the fuel detrapping rate. The inter-ELM fuel particle flux refills the partially emptied trapping sites and fills new sites. This leads to a competing effect on the retention and release rates of the implanted particles. At high temperatures the main retention appeared in larger vacancy clusters due to increased clustering rate

The effect of beryllium oxide on retention in JET ITER-like wall tiles

Preliminary results investigating the microstructure, bonding and effect of beryllium oxide formation on retention in the JET ITER-like wall beryllium tiles, are presented. The tiles have been investigated by several techniques: Scanning Electron Microscopy (SEM) equipped with Energy Dispersive X-ray (EDX), Transmission Electron microscopy (TEM) equipped with EDX and Electron Energy Loss Spectroscopy (EELS), Raman Spectroscopy and Thermal Desorption Spectroscopy (TDS). This paper focuses on results from melted materials of the dump plate tiles in JET. From our results and the literature, it is concluded, beryllium can form micron deep oxide islands contrary to the nanometric oxides predicted under vacuum conditions. The deepest oxides analyzed were up to 2-micron thicknesses. The beryllium Deuteroxide (BeOxDy) bond was found with Raman Spectroscopy. Application of EELS confirmed the oxide presence and stoichiometry. Literature suggests these oxides form at temperatures greater than 700 °C where self-diffusion of beryllium ions through the surface oxide layer can occur. Further oxidation is made possible between oxygen plasma impurities and the beryllium ions now present at the wall surface. Under Ultra High Vacuum (UHV) nanometric Beryllium oxide layers are formed and passivate at room temperature. After continual cyclic heating (to the point of melt formation) in the presence of oxygen impurities from the plasma, oxide growth to the levels seen experimentally (approximately two microns) is proposed. This retention mechanism is not considered to contribute dramatically to overall retention in JET, due to low levels of melt formation. However, this mechanism, thought the result of operation environment and melt formation, could be of wider concern to ITER, dependent on wall temperatures