p-Adic Models of Ultrametric Diffusion Constrained by Hierarchical Energy Landscapes

We demonstrate that p-adic analysis is a natural basis for the construction of a wide variety of the ultrametric diffusion models constrained by hierarchical energy landscapes. A general analytical description in terms of p-adic analysis is given for a class of models. Two exactly solvable examples, i.e. the ultrametric diffusion constraned by the linear energy landscape and the ultrametric diffusion with reaction sink, are considered. We show that such models can be applied to both the relaxation in complex systems and the rate processes coupled to rearrangenment of the complex surrounding.Comment: 14 pages, 6 eps figures, LaTeX 2.0

Aggression Following Traumatic brain injury: Effectiveness of Risperidone (AFTER): study protocol for a feasibility randomised controlled trial

Background: Traumatic brain injury (TBI) is a major public health concern and many people develop long-lasting physical and neuropsychiatric consequences following a TBI. Despite the emphasis on physical rehabilitation, it is the emotional and behavioural consequences that have greater impact on people with TBI and their families. One such problem behaviour is aggression which can be directed towards others, towards property or towards the self.Aggression is reported to be common after TBI (37–71%) and causes major stress for patients and their families.Both drug and non-drug interventions are used to manage this challenging behaviour, but the evidence-base for these interventions is poor and no drugs are currently licensed for the treatment of aggression following TBI. The most commonly used drugs for this purpose are antipsychotics, particularly second-generation drugs such as risperidone. Despite this widespread use, randomised controlled trials (RCTs) of antipsychotic drugs, including risperidone, have not been conducted. We have, therefore, set out to test the feasibility of conducting an RCT of this drug for people who have aggressive behaviour following TBI. Methods/design: We will examine the feasibility of conducting a placebo-controlled, double-blind RCT of risperidone for the management of aggression in adults with TBI and also assess participants’ views about their experience of taking part in the study. We will randomise 50 TBI patients from secondary care services in four centres in London and Kent to up to 4 mg of risperidone orally or an inert placebo and follow them up 12 weeks later. Participants will be randomised to active or control treatment in a 1:1 ratio via an external and remote web-based randomisation service. Participants will be assessed at baseline and 12-week follow-up using a battery of assessment scales to measure changes in aggressive behaviour (MOAS, IRQ) as well as global functioning (GOS-E, CGI), quality of life (EQ-5D-5L, SF-12) and mental health (HADS). We will also assess the adverse effect profile with a standard scale (UKU) and collect available data from medical records on blood tests (serum glucose/HbA1c, lipid profile, prolactin), and check body weight and blood pressure. In addition completion of the MOAS and a check for any new or worsening side-effect will be completed weekly and used by the prescribing clinician to determine continuing dosage. Family carers’ well being will be assessed with CWSQ. Service use will be recorded using CSRI. A process evaluation will be carried out at theend of the trial using both qualitative and quantitative methodology. Discussion: Aggressive behaviour causes immense distress among some people with TBI and their families. By examining the feasibility of a double-blind, placebo-controlled RCT, we aim to discover whether this approach can successfully be used to test the effects of risperidone for the treatment of aggressive behaviour among people with aggression following TBI and improve the evidence base for the treatment of these symptoms. Our criteria for demonstrating success of the feasibility study are: (1) recruitment of at least 80% of the study sample, (2) uptake of intervention by at least 80% of participants in the active arm of the trial and (3) completion of follow-up interviews at 12 weeks by at least 75% of the study participants

How to Enhance Qualitative Research Appraisal: Development of the Methodological Congruence Instrument

In this research report, we introduce a methodological congruence instrument (MCI) that addresses the five major qualitative research traditions. Methodological congruence is a fit between the researcher\u27s chosen methodology and his/her philosophical perspective. The chosen methodology should be aligned with the research question, data collection and sampling procedures, philosophical perspectives and seminal authors, data analysis, and findings. These elements are contained in the MCI. We share information about its inception, development, and application, and invite our research colleagues to offer critical feedback. It is our hope that qualitative researchers, editorial board members, teachers, and students find this instrument helpful and relevant to the application of qualitative research. As the qualitative research community continues to address questions of quality, the MCI may offer an additional layer of transparency that engenders scholarly discussion and furthers ethical writing, production, and publication

Risperidone versus placebo for aggression following traumatic brain injury: a feasibility randomised controlled trial

Objectives: To conduct a feasibility randomised controlled trial of risperidone for the treatment of aggression in adults with traumatic brain injury (TBI). Design: Multicentre, parallel design, placebo controlled (1:1 ratio) double-blind feasibility trial with an embedded process evaluation. No statistical comparison was performed between the two study groups. Setting: Four neuropsychiatric and neurology outpatient clinics in London and Kent, UK. Participants: Our aim was to recruit 50 patients with TBI over 18 months. Follow-up participants at 12 weeks using a battery of assessment scales to measure changes in aggressive behaviour and irritability (Modified Overt Aggression Scale (MOAS)-primary outcome, Irritability Questionnaire) as well as global functioning (Glasgow Outcome Scale-Extended, Clinical Global impression) and quality of life (EQ-5D-5L, SF-12), mental health (Hospital Anxiety and Depression Scale) and medication adverse effects (Udvalg for Kliniske Undersøgelser). Results: Six participants were randomised to the active arm of the trial and eight to the placebo arm over a 10-month period (28% of our target). Two participants withdrew because of adverse events. Twelve out of 14 (85.7%) patients completed a follow-up assessment at 12 weeks. At follow-up, the scores of all outcome measures improved in both groups. Placebo group showed numerically better score change according to the primary outcome MOAS. No severe adverse events were reported. The overall rate of adverse events remained low. Data from the process evaluation suggest that existence of specialised TBI follow-up clinics, availability of a dedicated database of TBI patients’ clinical details, simple study procedures and regular support to participants would enhance recruitment and retention in the trial. Feedback from participants showed that once in the study, they did not find the trial procedure onerous. Conclusions: It was not feasible to conduct a successful randomised trial of risperidone versus placebo for post-TBI aggression using the methods we deployed in this study. It is not possible to draw any definitive conclusion about risperidone’s efficacy from such a small trial. Trial registration number: ISRCTN3019143

p-Adic description of characteristic relaxation in complex systems

This work is a further development of an approach to the description of relaxation processes in complex systems on the basis of the p-adic analysis. We show that three types of relaxation fitted into the Kohlrausch-Williams-Watts law, the power decay law, or the logarithmic decay law, are similar random processes. Inherently, these processes are ultrametric and are described by the p-adic master equation. The physical meaning of this equation is explained in terms of a random walk constrained by a hierarchical energy landscape. We also discuss relations between the relaxation kinetics and the energy landscapes.Comment: AMS-LaTeX (+iopart style), 9 pages, submitted to J.Phys.

A proof of concept pilot trial of probiotics in symptomatic oral lichen planus (CABRIO)

OBJECTIVE: To preliminary evaluate the clinical effects of probiotics in individuals with symptomatic oral lichen planus and the possible mechanisms of action. SUBJECTS AND METHODS: A group of 30 individuals with symptomatic oral lichen planus were recruited in a randomised double-blind parallel group controlled (1:1) proof-of-concept pilot trial of probiotic VSL#3 vs placebo. Efficacy outcomes included changes in pain numeric rating scale, oral disease severity score and the chronic oral mucosal disease questionnaire. Adverse effects, home diary and withdrawals were assessed as feasibility outcomes. Mechanistic outcomes included changes in salivary and serum levels of CXCL10 and IFN-γ and in oral microbial composition. RESULTS: The probiotic VSL#3 was safe and well tolerated. We observed no statistically significant change in pain, disease activity, quality of life, serum/salivary CXCL10 or oral microbial composition with respect to placebo. Salivary IFN-γ levels demonstrate a trend for a reduced level in the active group (p = 0.082) after 30 days of probiotic consumption. CONCLUSIONS: The present proof-of-concept study provides some weak not convincing indication of biological and clinical effects of probiotic VSL#3 in individuals with painful oral lichen planus. Further research in this field is needed, with the current study providing useful information to the design of future clinical trials

More haste less speed: A meta-analysis of thinking latencies during planning in people with psychosis

Cognitive impairment is a core feature of psychosis, with slowed processing speed thought to be a prominent impairment in schizophrenia and first-episode psychosis. However, findings from the Stockings of Cambridge (SOC) planning task suggest changes in processing speed associated with the illness may include faster responses in early stages of planning, though findings are inconsistent. This review uses meta-analytic methods to assess thinking times in psychosis across the available literature. Studies were identified by searching PubMed, Web of Science and Google Scholar. Eligibility criteria: 1) included a sample of people with non-affective psychosis according to DSM III, DSM IV, DSM V or ICD-10 criteria; 2) employed the SOC task; 3) included a healthy control group; and 4) published in English. We identified 11 studies that employed the SOC task. Results show that people with psychosis have significantly faster initial thinking times than non-clinical participants, but significantly slower subsequent thinking times during problem execution. These findings indicate that differences in processing speed are not limited to slower responses in people with psychosis but may reflect a preference for step-by-step processing rather than planning before task execution. We suggest this style of responding is adopted to compensate for working memory impairment

Dissociable effects of 5-HT2C receptor antagonism and genetic inactivation on perseverance and learned non-reward in an egocentric spatial reversal task

Cognitive flexibility can be assessed in reversal learning tests, which are sensitive to modulation of 5-HT2C receptor (5-HT2CR) function. Successful performance in these tests depends on at least two dissociable cognitive mechanisms which may separately dissipate associations of previous positive and negative valence. The first is opposed by perseverance and the second by learned non-reward. The current experiments explored the effect of reducing function of the 5-HT2CR on the cognitive mechanisms underlying egocentric reversal learning in the mouse. Experiment 1 used the 5-HT2CR antagonist SB242084 (0.5 mg/kg) in a between-groups serial design and Experiment 2 used 5-HT2CR KO mice in a repeated measures design. Animals initially learned to discriminate between two egocentric turning directions, only one of which was food rewarded (denoted CS+, CS−), in a T- or Y-maze configuration. This was followed by three conditions; (1) Full reversal, where contingencies reversed; (2) Perseverance, where the previous CS+ became CS− and the previous CS− was replaced by a novel CS+; (3) Learned non-reward, where the previous CS− became CS+ and the previous CS+ was replaced by a novel CS-. SB242084 reduced perseverance, observed as a decrease in trials and incorrect responses to criterion, but increased learned non-reward, observed as an increase in trials to criterion. In contrast, 5-HT2CR KO mice showed increased perseverance. 5-HT2CR KO mice also showed retarded egocentric discrimination learning. Neither manipulation of 5-HT2CR function affected performance in the full reversal test. These results are unlikely to be accounted for by increased novelty attraction, as SB242084 failed to affect performance in an unrewarded novelty task. In conclusion, acute 5-HT2CR antagonism and constitutive loss of the 5-HT2CR have opposing effects on perseverance in egocentric reversal learning in mice. It is likely that this difference reflects the broader impact of 5HT2CR loss on the development and maintenance of cognitive function

Search for the Proton Decay Mode proton to neutrino K+ in Soudan 2

We have searched for the proton decay mode proton to neutrino K+ using the one-kiloton Soudan 2 high resolution calorimeter. Contained events obtained from a 3.56 kiloton-year fiducial exposure through June 1997 are examined for occurrence of a visible K+ track which decays at rest into mu+ nu or pi+ pi0. We found one candidate event consistent with background, yielding a limit, tau/B > 4.3 10^{31} years at 90% CL with no background subtraction.Comment: 13 pages, Latex, 3 tables and 3 figures, Accepted by Physics Letters