Mechanism of action of 5-arninosalicylic acid

5-Aminosalicylic Acid (5-ASA) has been used for over 50 years in the treatment of inflammatory bowel disease in the pro-drug form sulphasalazine (SASP). SASP is also used to treat rheumatoid arthritis. However whether the therapeutic properties of SASP are due to the intact molecule, the 5-ASA or sulphapyridine components is unknown. Several mechanisms of action have been proposed for 5-ASA and SASP including interference in the metabolism of arachidonic acid to prostaglandins and leukotrienes, scavenging,of reactive oxygen species, effects on leucocyte function and production of cytokines. However, it is unlikely that the anti-inflammatory properties of SASP and 5-ASA are due to several different properties but more likely that a single property of 5-ASA explains the theraapeutic effects of 5-ASA and SASP. Reactive oxygen species (ROS) are involved in the metabolism of prostaglandins and leukotrienes and can act as second messengers, and so the scavenging of ROS may be the single mechanism of action of 5-ASA that gives rise to its antiinflammatory effects in both inflammatory bowel disease and rheumatoid arthritis

Crustal Deformation and Fault Strength of the Sulawesi Subduction Zone

This paper investigates the seismicity and rheology of the North-Sulawesi subduction zone. Body-wave modeling is used to estimate focal mechanisms and centroid depths of moderate magnitude (M5–M6.5) earthquakes on the North Sulawesi megathrust and surrounding region. The slip vectors of megathrust earthquakes radiate outward from Sulawesi, indicating motion that is incompatible with the relative motion of two rigid plates. Instead, the observed deformation implies lateral spreading of high topography, controlled by gravitational potential energy contrasts. This finding suggests that the observed deformation of Sulawesi results from stresses transmitted through the lithosphere, rather than basal tractions due to circulation in the mantle. Our modeling of the force balance on the megathrust shows that the subduction megathrust is weak, with an average shear stress of ∼13 MPa and an effective coefficient of friction of 0.03. Elsewhere in Sulawesi, slip vectors of other earthquakes suggest similar potential-energy-driven deformation is present, but at significantly slower rates. Our results show the importance of lateral rheology contrasts in determining deformation rate, and hence seismic hazard, in response to a given driving force.Newton Institutional Links Leverhulme Fellowshi

Improving multidisciplinary team working to support integrated care for people with frailty amidst the COVID-19 pandemic

Multidisciplinary team (MDT) working is essential to optimise and integrate services for people who are frail. MDTs require collaboration. Many health and social care professionals have not received formal training in collaborative working. This study investigated MDT training designed to help participants deliver integrated care for frail individuals during the Covid-19 pandemic. Researchers utilised a semi-structured analytical framework to support observations of the training sessions and analyse the results of two surveys designed to assess the training process and its impact on participants knowledge and skills. 115 participants from 5 Primary Care Networks in London attended the training. Trainers utilised a video of a patient pathway, encouraged discussion of it, and demonstrated the use of evidence-based tools for patient needs assessment and care planning. Participants were encouraged to critique the patient pathway, reflect on their own experiences of planning and providing patient care. 38% of participants completed a pre-training survey, 47% a post-training survey. Significant improvement in knowledge and skills were reported including understanding roles in contributing to MDT working, confidence to speak in MDT meetings, using a range of evidence-based clinical tools for comprehensive assessment and care planning. Greater levels of autonomy, resilience, and support for MDT working were reported. Training proved effective; it could be scaled up and adopted to other settings

Gender differences in the Force Concept Inventory for different educational levels in the United Kingdom

The Force Concept Inventory (FCI) is widely used to investigate the effect of education level on conceptual understanding of Newtonian mechanics but has only recently been scrutinized for gender effects and retention. This study examines both the gender gap in first year physics undergraduates compared to the gap for nonphysicists and the FCI retention after three months. All participants were either studying or working at the University of Sheffield in the UK and had completed a similar compulsory level of secondary education. As expected the results show that a greater level of education in physics is associated with a larger average FCI score. However, further analysis shows that there exists a gender gap at all levels of education. The size of the effect of gender is quantified using Cohen’s d and ranges from 0.84 to 1.17 which indicates a large effect due to gender for all levels of education. Despite the FCI having been used as a tool to measure learning gains immediately following instruction in Newtonian mechanics there has been little work to investigate whether this increase in FCI score remains after some time has elapsed. Here the increase in FCI scores is found to remain increased after a three month absence of mechanics-related teaching, and that this retention of FCI scores is independent of gender. Despite this, the gender gap still remains large and statistically significant after the three month delay

Attitudes and barriers to exercise in adults with type 1 diabetes (T1DM) and how best to address them: a qualitative study

This is the final version. Available on open access from Public Library of Science via the DOI in this recordData Availability: The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper.BACKGROUND: Regular physical activity has recognised health benefits for people with T1DM. However a significant proportion of them do not undertake the recommended levels of activity. Whilst questionnaire-based studies have examined barriers to exercise in people with T1DM, a formal qualitative analysis of these barriers has not been undertaken. Our aims were to explore attitudes, barriers and facilitators to exercise in patients with T1DM. METHODOLOGY: A purposeful sample of long standing T1DM patients were invited to participate in this qualitative study. Twenty-six adults were interviewed using a semi-structured interview schedule to determine their level of exercise and barriers to initiation and maintenance of an exercise programme. PRINCIPAL FINDINGS: Six main barriers to exercise were identified: lack of time and work related factors; access to facilities; lack of motivation; embarrassment and body image; weather; and diabetes specific barriers (low levels of knowledge about managing diabetes and its complications around exercise). Four motivators to exercise were identified: physical benefits from exercise; improvements in body image; enjoyment and the social interaction of exercising at gym or in groups. Three facilitators to exercise were identified: free or reduced admission to gyms and pools, help with time management, and advice and encouragement around managing diabetes for exercise. SIGNIFICANCE: Many of the barriers to exercise in people with T1DM are shared with the non-diabetic population. The primary difference is the requirement for education about the effect of exercise on diabetes control and its complications. There was a preference for support to be given on a one to one basis rather than in a group environment. This suggests that with the addition of the above educational requirements, one to one techniques that have been successful in increasing activity in patients with other chronic disease and the general public should be successful in increasing activity in patients with T1DM.Insulin Dependent Diabetes Trus

Exercise to preserve beta cell function in recent-onset type 1 diabetes mellitus (EXTOD) - a study protocol for a pilot randomized controlled trial

BACKGROUND: Exercise has a beta cell preserving effect in patients with type 2 diabetes. This benefit of exercise has not been examined in type 1 diabetes. Significant beta cell function is present at the time of diagnosis of type 1 diabetes and therefore studies of beta cell preservation are ideally conducted immediately after diagnosis.Many of the variables required to design and power such a study are currently unknown. The aim of EXTOD is to obtain the information required to design a formal study of exercise and beta cell preservation in newly diagnosed patients with type 1 diabetes. METHODS: Barriers to exercise will initially be assessed in a qualitative study of newly diagnosed patients. Then, sixty newly diagnosed adult type 1 diabetes patients will be randomized to either conventional treatment or exercise, stratified on beta cell function and fitness. The exercise group will be encouraged to increase their level of activity to a minimum of 150 minutes of moderate to vigorous intensity exercise per week, aiming for 240 minutes per week of exercise for 12 months. Beta cell function will be measured by meal-stimulated C peptide. Primary outcomes are recruitment, adherence to exercise, loss to follow-up, and exercise levels in the non-intervention arm (contamination). The secondary outcome of the study is rate of loss of beta cell function. DISCUSSION: The outcomes of the EXTOD study will help define the barriers, uptake and benefits of exercise in adults newly diagnosed with type 1 diabetes. This information will enable design of a formal study to assess the effect of exercise on beta cell preservation in newly diagnosed patients with type 1 diabetes. TRIAL REGISTRATION: Current controlled trials ISRCTN91388505.Funding is provided by the Research for Patient Benefit (RfPB) stream of the National Institute for Health Research UK

Patient-initiated second medical consultations: patient characteristics and motivating factors, impact on care and satisfaction: A systematic review

Objectives: To review the characteristics and motivations of patients seeking second opinions, and the impact of such opinions on patient management, satisfaction, and cost-effectiveness. Data sources: Embase, Medline, PsycINFO and HMIC databases. Study design: A systematic literature search was performed for terms related to second opinion and patient characteristics. Study quality was assessed using the National Institutes of Health (NIH) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Data collection / Extraction methods: We included articles focused on patient-initiated second opinions, which provided quantitative data on their impact on diagnosis, treatment, prognosis or patient satisfaction, described the characteristics or motivating factors of patients who initiated a second opinion, or the cost-effectiveness of patient-initiated second opinions. Principal findings: Thirty-one articles were included in the review. 27 studies considered patient characteristics, 18 patient motivating factors, 10 patient satisfaction, and 17 clinical agreement between the first and second opinion. Seeking a second opinion was more common in women, middle age patients, more educated patients; and in people having a chronic condition, with higher income or socioeconomic status or living in central urban areas. Patients seeking a second opinion sought to gain more information or reassurance about their diagnosis or treatment. While many second opinions confirm the original diagnosis or treatment, discrepancies in opinions had a potential major impact on patient outcomes in up to 58% of cases. No studies reporting on the cost-effectiveness of patient initiated second opinions. Conclusions: Seeking a second opinion was more common in women, middle-age patients, and more educated patients, and in people having a chronic condition, with higher income or socioeconomic status or living in central urban areas. Patients seeking a second opinion sought to gain more information or reassurance about their diagnosis or treatment