The Diabetes Manual trial protocol – a cluster randomized controlled trial of a self-management intervention for type 2 diabetes [ISRCTN06315411]

Background The Diabetes Manual is a type 2 diabetes self-management programme based upon the clinically effective 'Heart Manual'. The 12 week programme is a complex intervention theoretically underpinned by self-efficacy theory. It is a one to one intervention meeting United Kingdom requirements for structured diabetes-education and is delivered within routine primary care. Methods/design In a two-group cluster randomized controlled trial, GP practices are allocated by computer minimisation to an intervention group or a six-month deferred intervention group. We aim to recruit 250 participants from 50 practices across central England. Eligibility criteria are adults able to undertake the programme with type 2 diabetes, not taking insulin, with HbA1c over 8% (first 12 months) and following an agreed protocol change over 7% (months 13 to 18). Following randomisation, intervention nurses receive two-day training and delivered the Diabetes Manual programme to participants. Deferred intervention nurses receive the training following six-month follow-up. Primary outcome is HbA1c with total and HDL cholesterol; blood pressure, body mass index; self-efficacy and quality of life as additional outcomes. Primary analysis is between-group HbA1c differences at 6 months powered to give 80% power to detect a difference in HbA1c of 0.6%. A 12 month cohort analysis will assess maintenance of effect and assess relationship between self-efficacy and outcomes, and a qualitative study is running alongside. Discussion This trial incorporates educational and psychological diabetes interventions into a single programme and assesses both clinical and psychosocial outcomes. The trial will increase our understanding of intervention transferability between conditions, those diabetes related health behaviours that are more or less susceptible to change through efficacy enhancing mechanisms and how this impacts on clinical outcomes

Sympathomimetic effects of chronic methamphetamine abuse on oral health: a cross-sectional study

Background: Methamphetamine, a highly addictive sympathomimetic stimulant, is currently widely abused worldwide and has been associated with devastating effects on oral health, resulting in the term "meth mouth". However, "meth mouth" pathology is primarily based on case reports with a lack of systematic clinical evaluation. Therefore, we have conducted a systematic study to investigate (1) the pharmacological impact of methamphetamine on oral health with regard to saliva function, including the parameters saliva flow rate and total saliva production (ml/5 min) and the buffering capacity of saliva;(2) the contribution of the symptoms of bruxism and muscle trismus to potential oral health damage. Methods: We assessed the data of 100 chronic methamphetamine abusers and 100 matched-pair comparison participants. Primarily, we conducted an anamnesis with all methamphetamine abusers with regard to saliva dysfunctions, jaw clenching and pain in the temporomandibular joint. Subsequently, in the first part of the clinical enquiry, we tested the saliva flow rate and the total saliva production (ml/5 min) by using the sialometry method and the buffer capacity of saliva by determining the pH-value. In the second part of the clinical enquiry, we evaluated bruxism symptoms with respect to generalized tooth attrition, dentine exposure and visible enamel cracks and examined a potential muscle trismus by measuring the maximal opening of the mouth. Results: The majority of methamphetamine abusers reported a dry mouth (72 %) and jaw clenching (68 %). Almost half of all methamphetamine abusers experienced pain in the temporomandibular joint (47 %). With regard to the clinical findings, methamphetamine abusers showed significantly lower total saliva production (ml/5 min) (p 0.05). Conclusions: The sympathomimetic effects of chronic methamphetamine abuse may lead to dry mouth and extensive bruxism and therefore can increase the risk for caries decay, periodontal lesions and tooth wear. Furthermore, a significant decline of saliva buffer capacity in methamphetamine abusers may trigger the risk for dental erosions. Methamphetamine abusers and practitioners should be aware of these symptoms

Oxytocin attenuates feelings of hostility depending on emotional context and individuals' characteristics

In humans, oxytocin (OT) enhances prosocial behaviour. However, it is still unclear how the prosocial effects of OT are modulated by emotional features and/or individuals' characteristics. In a placebo-controlled design, we tested 20 healthy male volunteers to investigate these behavioural and neurophysiological modulations using magnetoencephalography. As an index of the individuals' characteristics, we used the empathy quotient (EQ), the autism spectrum quotient (AQ), and the systemising quotient (SQ). Only during the perception of another person's angry face was a higher SQ a significant predictor of OT-induced prosocial change, both in the behavioural and neurophysiological indicators. In addition, a lower EQ was only a significant predictor of OT-induced prosocial changes in the neurophysiological indicators during the perception of angry faces. Both on the behavioural and the neurophysiological level, the effects of OT were specific for anger and correlated with a higher SQ

Common Gene Therapy Viral Vectors Do Not Efficiently Penetrate Sputum from Cystic Fibrosis Patients

Norwalk virus and human papilloma virus, two viruses that infect humans at mucosal surfaces, have been found capable of rapidly penetrating human mucus secretions. Viral vectors for gene therapy of Cystic Fibrosis (CF) must similarly penetrate purulent lung airway mucus (sputum) to deliver DNA to airway epithelial cells. However, surprisingly little is known about the rates at which gene delivery vehicles penetrate sputum, including viral vectors used in clinical trials for CF gene therapy. We find that sputum spontaneously expectorated by CF patients efficiently traps two viral vectors commonly used in CF gene therapy trials, adenovirus (d∼80 nm) and adeno-associated virus (AAV serotype 5; d∼20 nm), leading to average effective diffusivities that are ∼3,000-fold and 12,000-fold slower than their theoretical speeds in water, respectively. Both viral vectors are slowed by adhesion, as engineered muco-inert nanoparticles with diameters as large as 200 nm penetrate the same sputum samples at rates only ∼40-fold reduced compared to in pure water. A limited fraction of AAV exhibit sufficiently fast mobility to penetrate physiologically thick sputum layers, likely because of the lower viscous drag and smaller surface area for adhesion to sputum constituents. Nevertheless, poor penetration of CF sputum is likely a major contributor to the ineffectiveness of viral vector based gene therapy in the lungs of CF patients observed to date

The SUN Protein Mps3 Is Required for Spindle Pole Body Insertion into the Nuclear Membrane and Nuclear Envelope Homeostasis

The budding yeast spindle pole body (SPB) is anchored in the nuclear envelope so that it can simultaneously nucleate both nuclear and cytoplasmic microtubules. During SPB duplication, the newly formed SPB is inserted into the nuclear membrane. The mechanism of SPB insertion is poorly understood but likely involves the action of integral membrane proteins to mediate changes in the nuclear envelope itself, such as fusion of the inner and outer nuclear membranes. Analysis of the functional domains of the budding yeast SUN protein and SPB component Mps3 revealed that most regions are not essential for growth or SPB duplication under wild-type conditions. However, a novel dominant allele in the P-loop region, MPS3-G186K, displays defects in multiple steps in SPB duplication, including SPB insertion, indicating a previously unknown role for Mps3 in this step of SPB assembly. Characterization of the MPS3-G186K mutant by electron microscopy revealed severe over-proliferation of the inner nuclear membrane, which could be rescued by altering the characteristics of the nuclear envelope using both chemical and genetic methods. Lipid profiling revealed that cells lacking MPS3 contain abnormal amounts of certain types of polar and neutral lipids, and deletion or mutation of MPS3 can suppress growth defects associated with inhibition of sterol biosynthesis, suggesting that Mps3 directly affects lipid homeostasis. Therefore, we propose that Mps3 facilitates insertion of SPBs in the nuclear membrane by modulating nuclear envelope composition

Management control systems in innovation companies: A literature based framework

Past research has traditionally argued that management control systems (MCSs) may present a hindrance to the creativity of innovation companies. This theoretical paper surveys the literature to focus an investigation on the MCSs of innovation companies. Within the object of control paradigm the paper develops and presents a theoretical model of the impact of eleven external, organisational and innovation related contingency factors on the MCSs in companies that engage in innovation activities. We also suggest measures for further empirical research. By formulating hypotheses on 43 potential interactions the model predicts contradictory influences on two direct control categories, results and action control, but stresses the importance of two indirect categories, personnel and cultural control. More specifically, the high levels of technological complexity and innovation capability in this type of company are expected to be negatively associated with the application of results and action control, whereas personnel and cultural seem to be more appropriate. Furthermore, important sources of finance, venture capital and public funding, are both hypothesised to be positively associated with the application of results, action and personnel control; whereas only public funding is predicted to be positively related to the application of cultural control. The principal contribution of this paper lies in synthesising the literature to provide a model of the impact of a unique set of eleven contingency factors for innovation companies on a broad scope of controls. In addition, the contingency model, if empirically validated, would add value by inferring the particular forms of management control which would be beneficial in innovative company settings. © 2014 Springer-Verlag Berlin Heidelberg