A pilot randomised controlled trial of an internet-based cognitive behavioural therapy self-management programme (MS Invigor8) for multiple sclerosis fatigue

The majority of people affected by Multiple Sclerosis (PaMS) experience severe and disabling fatigue. MS Fatigue is poorly understood and most existing treatments have limited effectiveness. However, a recent randomised controlled trial (RCT) showed that cognitive-behaviour therapy with a clinical psychologist was effective in reducing MS fatigue severity and impact. The current study developed an Internet-based version of this intervention to make it available to a wider group of PaMS and conducted preliminary investigations of its efficacy, feasibility and cost-effectiveness in a pilot RCT. The ‘MS Invigor8’ website was developed using agile design and substantial input from PaMS. The programme includes eight online tailored and interactive sessions along with homework tasks, intended to be accessed weekly. In the pilot trial, 40 patients were randomised to MS Invigor8 (n=23) or standard care (n=17). The MS Invigor8 group accessed sessions over 8-10 weeks and received up to three 30-50 minute telephone support sessions. Participants completed online questionnaires assessing fatigue, mood and quality of life at baseline and 10 weeks follow-up. Large between group treatment effects were found for the primary outcomes of fatigue severity (d=1.19) and impact (d =1.22). The MS Invigor8 group also reported significantly greater improvements in anxiety and depression. Analysis suggested that the intervention may be cost-effective. Qualitative feedback suggested that participants considered this treatment approach acceptable and helpful. Technical website problems negatively affected some users’ experiences and need to be resolved. Given the promising results a larger RCT with longer term follow-up is warranted. <br/

The ethical role of computational linguistics in digital psychological formulation and suicide prevention.

Formulation is central to clinical practice. Formulation has a factor weighing, pattern recognition and explanatory hypothesis modelling focus. Formulation attempts to make sense of why a person presents in a certain state at a certain time and context, and how that state may be best managed to enhance mental health, safety and optimal change. Inherent to the clinical need for formulation is an appreciation of the complexities, uncertainty and limits of applying theoretical concepts and symptom, diagnostic and risk categories to human experience; or attaching meaning or weight to any particular factor in an individual's history or mental state without considering the broader biopsychosocial and cultural context. With specific reference to suicide prevention, this paper considers the need and potential for the computer linguistic community to be both cognisant of and ethically contribute to the clinical formulation process

NMR Simulation of an Eight-State Quantum System

The propagation of excitation along a one-dimensional chain of atoms is simulated by means of NMR. The physical system used as an analog quantum computer is a nucleus of 133-Cs (spin 7/2) in a liquid crystalline matrix. The Hamiltonian of migration is simulated by using a special 7-frequency pulse, and the dynamics is monitored by following the transfer of population from one of the 8 spin energy levels to the other.Comment: 10 pages, 3 figure

Effect of wheat distillers dried grains with solubles or sugar beet pulp on prevalence of Salmonella enterica Typhimurium in weaned pigs

Salmonella enterica Typhimurium (ST) is of concern in the swine industry with relevance for animal health and consumer safety. Nutritional strategies might help to reduce ST infection and transmission. This study examined the potential of wheat (Triticum aestivum) distillers dried grains with solubles (DDGS) and sugar beet (Beta vulgaris) pulp (SBP) to alter intestinal microbial communities and ST shedding using a Trojan model. Weaned pigs (n = 105; 28.5 ± 3.5 d of age) were separated into 3 treatment groups (7 pigs/pen) and fed a wheat-based control diet or the control diet formulated with 15% wheat DDGS or 6% SBP inclusion. Following 12 d of diet adaptation, 2 pigs/pen were inoculated with 2 x 109 cfu ST, resistant to novobiocin and nalidixic acid. Fecal swabs were taken from infected pigs and pen-mates (contact pigs) for 9 d following challenge, enriched in nutrient broth for 24 h, and plated on selective media to determine prevalence of ST. The ranges of prevalence of ST in feces were from 90 to 100% in challenged pigs and 74 to 78% in contact pigs. No influence of treatment on rectal temperature and prevalence of ST in contact pigs were observed. Fifteen contact pigs were euthanized per treatment group on 9 and 10 d postchallenge to enumerate in intestinal contents (ileum, cecum, and proximal colon), Lactobacillus spp., Enterobacteriaceae, and Clostridium clusters I, VI, and XVIa by quantitative PCR (qPCR) and to determine ST prevalence by selective culture. No significant effects of diet were observed with respect to ST prevalence in feces, ileum, cecum, colon, and lymph nodes of contact pigs. Compared with the control diet, DGGS and SBP diets showed a trend towards increased (P < 0.1) number of Lactobacillus species in the cecum and colon. Although both wheat DGGS and SBP tended to increase the Lactobacillus spp. neither of the feed ingredients affected ST prevalence

Early IL-1 signaling promotes iBALT induction after influenza virus infection

Inducible bronchus-associated lymphoid tissue (iBALT) is a long lasting tertiary lymphoid tissue that can be induced following influenza A virus (IAV) infection. Previous studies have shown that iBALT structures containing germinal center (GC) B cells protect against repeated infection by contributing locally to the cellular and humoral immune response. If we are to exploit this in vaccination strategies, we need a better understanding on how iBALT structures are induced. One hypothesis is that the strength of the initial innate response dictates induction of iBALT. In the present study, we investigated the role of interleukin (IL)-1 and IL-1R signaling on iBALT formation. Mice lacking the IL-1R had a delayed viral clearance and, thus, a prolonged exposure to viral replication, leading to increased disease severity, compared to wild-type mice. Contradictorily, iBALT formation following clearance of the virus was heavily compromised in Il1r1-/- mice. Quantification of gene induction after IAV infection demonstrated induction of IL-1α and to a much lesser extent of IL-1β. Administration of recombinant IL-1α to the lungs of wild-type mice, early but not late, after IAV infection led to more pronounced iBALT formation and an increased amount of GC B cells in the lungs. Bone marrow chimeric mice identified the stromal compartment as the crucial IL-1 responsive cell for iBALT induction. Mechanistically, Q-PCR analysis of lung homogenates revealed a strongly diminished production of CXCL13, a B cell-attracting chemokine, in Il1r-/- mice during the early innate phase of IAV infection. These experiments demonstrate that appropriate innate IL-1α-IL-1R signaling is necessary for IAV clearance and at the same time instructs the formation of organized tertiary lymphoid tissues through induction of CXCL13 early after infection. These findings are discussed in the light of recent insights on the pathogenesis of tertiary lymphoid organ formation in the lung in various diseases where the IL-1 axis is hyperactive, such as rheumatoid arthritis and COPD