The ascent of kimberlite: Insights from olivine

Olivine xenocrysts are ubiquitous in kimberlite deposits worldwide and derive from the disaggregation of mantle-derived peridotitic xenoliths. Here, we provide descriptions of textural features in xenocrystic olivine from kimberlite deposits at the Diavik Diamond Mine, Canada and at Igwisi Hills volcano, Tanzania. We establish a relative sequence of textural events recorded by olivine during magma ascent through the cratonic mantle lithosphere, including: xenolith disaggregation, decompression fracturing expressed as mineral- and fluid-inclusion-rich sealed and healed cracks, grain size and shape modification by chemical dissolution and abrasion, late-stage crystallization of overgrowths on olivine xenocrysts, and lastly, mechanical milling and rounding of the olivine cargo prior to emplacement. Ascent through the lithosphere operates as a “kimberlite factory” wherein progressive upward dyke propagation of the initial carbonatitic melt fractures the overlying mantle to entrain and disaggregate mantle xenoliths. Preferential assimilation of orthopyroxene (Opx) xenocrysts by the silica-undersaturated carbonatitic melt leads to deep-seated exsolution of CO2-rich fluid generating buoyancy and supporting rapid ascent. Concomitant dissolution of olivine produces irregular-shaped relict grains preserved as cores to most kimberlitic olivine. Multiple generations of decompression cracks in olivine provide evidence for a progression in ambient fluid compositions (e.g., from carbonatitic to silicic) during ascent. Numerical modelling predicts tensile failure of xenoliths (disaggregation) and olivine (cracks) over ascent distances of 2–7 km and 15–25 km, respectively, at velocities of 0.1 to >4 m s−1. Efficient assimilation of Opx during ascent results in a silica-enriched, olivine-saturated kimberlitic melt (i.e. SiO2 >20 wt.%) that crystallizes overgrowths on partially digested and abraded olivine xenocrysts. Olivine saturation is constrained to occur at pressures <1 GPa; an absence of decompression cracks within olivine overgrowths suggests depths <25 km. Late stage (<25 km) resurfacing and reshaping of olivine by particle–particle milling is indicative of turbulent flow conditions within a fully fluidized, gas-charged, crystal-rich magma

The Potential Impact of Displacing Sedentary Time in Adults with Type 2 Diabetes.

This is the final published version. Available from Lippincott, Williams & Wilkins via the DOI in this record.PURPOSE: Sedentary time, in particular, prolonged unbroken sedentary time, is detrimental to health and displaces time spent in either light or moderate intensity physical activity. This cross-sectional study aimed to identify the potential impact of reallocating time from sedentary behaviors to more active behaviors on measures of body composition and metabolic health in people with type 2 diabetes. METHODS: Participants were 519 adults with newly diagnosed type 2 diabetes who had been recruited to the Early Activity in Diabetes (Early ACTID) randomized controlled trial. Waist-worn accelerometers were used to obtain objective measurement of sedentary time, light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA) at baseline alongside clinical measurements and fasting blood samples to determine cholesterol, triglycerides, HOMA-IR, and glucose. Isotemporal substitution modeling was performed to determine the potential impact of reallocating 30 min of sedentary time accumulated in a single bout (long bout) with 30 min of interrupted sedentary time, LPA, or MVPA. RESULTS: Sedentary time accounted for 65% of the waking day, of which 45% was accumulated in prolonged (≥30 min) bouts. Reallocation of 30 min of long-bout sedentary time with 30 min of short-bout sedentary time was associated with lower body mass index (BMI) (adjusted β, -0.60; 95% confidence interval [CI], -1.00, -0.21) and waist circumference (WC) (adjusted β, -1.16; 95% CI, -2.08, -0.25). Stronger effects were seen for LPA and MVPA. Reallocation of 30 min of long-bout sedentary time with LPA was associated with higher HDL-cholesterol (adjusted β, 0.02; 95% CI, 0.00-0.03 mmol·L). CONCLUSIONS: Encouraging adults with newly diagnosed type 2 diabetes to break up prolonged periods of sedentary time may be an effective strategy for improving body composition and metabolic health.National Institute for Health Research (NIHR

Phase I clinical trial of the Src inhibitor dasatinib with dacarbazine in metastatic melanoma.

BackgroundSrc inhibitors sensitise melanoma cells to chemotherapy in preclinical models. The combination of dasatinib and dacarbazine was tested in a phase I trial in melanoma.MethodsPatients had ECOG performance status 0-2 and normal organ function. Dacarbazine was administered on day 1 and dasatinib on day 2 through 19 of each 21-day cycle. Both were escalated from 50 mg b.i.d. of dasatinib and 800 mg m(-2) of dacarbazine. Available pre-treatment biopsies were sequenced for BRAF, NRAS, and C-Kit mutations.ResultsDose-limiting toxicity was reached at dasatinib 70 mg b.i.d./dacarbazine 1000 mg m(-2), and was predominantly haematological. In 29 patients receiving dasatinib 70 mg b.i.d., the objective response rate (ORR) was 13.8%, the clinical benefit rate (ORR+SD) was 72.4%, the 6-month progression-free survival (PFS) was 20.7%, and the 12-month overall survival (OS) was 34.5%. Two out of three patients who were wild type for BRAF, NRAS, and c-KIT mutations had confirmed partial responses, and one had a minor response.ConclusionThe recommended phase II dose is dasatinib 70 mg b.i.d with dacarbazine 800 mg m(-2). PFS and OS data for dasatinib at 70 mg b.i.d. with dacarbazine compared favourably with historical controls. Preliminary data support evaluating tumour mutation status further as a biomarker of response

Dietary changes and associations with metabolic improvements in adults with type 2 diabetes during a patient-centred dietary intervention: an exploratory analysis.

This is the final published version. Available from BMJ Publishing Group via the DOI in this record.OBJECTIVES: Describe dietary intake of participants enrolled in a non-prescriptive dietary intervention and dietary changes at 6 months and explore whether these changes had a role in observed improvements in glycated haemoglobin (HbA1c), weight, lipids and blood pressure. DESIGN: Secondary analysis of data from the Early ACTivity in Diabetes randomised controlled trial. PARTICIPANTS: 262 patients with newly diagnosed type 2 diabetes randomised to the dietary intervention. OUTCOMES AND ANALYSIS: Changes in energy intake, macronutrients, fibre and alcohol and in weight, waist circumference, lipids, HbA1c and blood pressure at baseline and 6 months. Multivariate models were used to examine associations between dietary changes and metabolic variables. RESULTS: Men reported reducing mean energy intake from 1903±462 kcal to 1685 kcal±439 kcal (p<0.001), increasing carbohydrate intake from 42.4±6.6% to 43.8±6.6% (p=0.002) and reducing median alcohol intake from 13 (0-27) g to 5 (0-18) g (p<0.001). Women reported reducing mean energy intake from 1582±379 kcal to 1459±326 kcal (p<0.001) with no change to macronutrient distribution and alcohol. Fibre intake was maintained. In men (n=148), weak and clinically insignificant associations were found between increased carbohydrates and reduction in HbA1c (β=-0.003 (-0.006, -0.001); p=0.009), increased fibre and reduction in total cholesterol (β=-0.023 (-0.044, -0.002); p=0.033), decreased total fat and reduction in low-density lipoprotein (LDL)-cholesterol (β=0.024 (0.006, 0.001); p=0.011), and decreased alcohol and reduction in diastolic blood pressure (β=0.276 (0.055, 0.497); p=0.015). In women (n=75), associations were found between a decrease in transfats and reductions in waist circumference (β=-0.029 (0.006, 0.052); p=0.015), total cholesterol (β=0.399 (0.028, 0.770); p=0.036) and LDL cholesterol (β=0.365 (0.042, 0.668); p=0.028). CONCLUSIONS: Clinically important metabolic improvements observed in a patient-centred dietary intervention were not explained by changes in macronutrients. However, a non-prescriptive approach may promote a reduction in total energy intake while maintaining fibre consumption. TRIAL REGISTRATION NUMBER: The Early ACTID trial number ISRCTN92162869.Diabetes UKUK Department of HealthWestern Comprehensive Local Research NetworkNational Institute for Health Research (NIHR

Development of a brief, reliable and valid diet assessment tool for impaired glucose tolerance and diabetes: the UK Diabetes and Diet Questionnaire.

This is the final published version. Available from Cambridge University Press via the DOI in this record.OBJECTIVE: Dietary advice is fundamental in the prevention and management of type 2 diabetes (T2DM). Advice is improved by individual assessment but existing methods are time-consuming and require expertise. We developed a twenty-five-item questionnaire, the UK Diabetes and Diet Questionnaire (UKDDQ), for quick assessment of an individual's diet. The present study examined the UKDDQ's repeatability and relative validity compared with 4 d food diaries. DESIGN: The UKDDQ was completed twice with a median 3 d gap (interquartile range=1-7 d) between tests. A 4 d food diary was completed after the second UKDDQ. Diaries were analysed and food groups were mapped on to the UKDDQ. Absolute agreement between total scores was examined using intra-class correlation (ICC). Agreement for individual items was tested with Cohen's weighted kappa (κ w). SETTING: South West of England. SUBJECTS: Adults (n 177, 50·3 % women) with, or at high risk for, T2DM; mean age 55·8 (sd 8·6) years, mean BMI 34·4 (sd 7·3) kg/m2; participants were 91 % White British. RESULTS: The UKDDQ showed excellent repeatability (ICC=0·90 (0·82, 0·94)). For individual items, κ w ranged from 0·43 ('savoury pastries') to 0·87 ('vegetables'). Total scores from the UKDDQ and food diaries compared well (ICC=0·54 (0·27, 0·70)). Agreement for individual items varied and was good for 'alcohol' (κ w=0·71) and 'breakfast cereals' (κ w=0·70), with no agreement for 'vegetables' (κ w=0·08) or 'savoury pastries' (κ w=0·09). CONCLUSIONS: The UKDDQ is a new British dietary questionnaire with excellent repeatability. Comparisons with food diaries found agreements similar to those for international dietary questionnaires currently in use. It targets foods and habits important in diabetes prevention and management.National Institute for Health Research (NIHR)Avon Primary Care Research CollaborativeNational Institute for Health Research (NIHR

Attitudes and barriers to exercise in adults with a recent diagnosis of type 1 diabetes: a qualitative study of participants in the Exercise for Type 1 Diabetes (EXTOD) study

This is the final published version. Available from BMJ Publishing via the DOI in this record.All data underlying the findings are fully available without restriction. All relevant data are within the paperObjectives To explore attitudes and barriers to exercise in adults with new-onset type 1 diabetes mellitus (T1DM). Design Qualitative methodology using focus group (n=1), individual face-to-face (n=4) and telephone interviews (n=8). Thematic analysis using the Framework Method. Setting Nineteen UK hospital sites. Participants Fifteen participants in the Exercise for Type 1 Diabetes study. We explored current and past levels of exercise, understanding of exercise and exercise guidelines, barriers to increasing exercise levels and preferences for monitoring of activity in a trial. Results Five main themes were identified: existing attitudes to exercise, feelings about diagnosis, perceptions about exercise consequences, barriers to increasing exercise and confidence in managing blood glucose. An important finding was that around half the participants reported a reduction in activity levels around diagnosis. Although exercise was felt to positively impact on health, some participants were not sure about the benefits or concerned about potential harms such as hypoglycaemia. Some participants reported being advised by healthcare practitioners (HCPs) not to exercise. Conclusions Exercise should be encouraged (not discouraged) from diagnosis, as patients may be more amenable to lifestyle change. Standard advice on exercise and T1DM needs to be made available to HCPs and patients with T1DM to improve patients’ confidence in managing their diabetes around exercise. Trial registration number ISRCTN91388505; ResultsNational Institute for Health Research (NIHR)National Institute for Health Research (NIHR

"I've made this my lifestyle now": a prospective qualitative study of motivation for lifestyle change among people with newly diagnosed type two diabetes mellitus

This is the final published version. Available from BMC via the DOI in this record.The datasets generated and/or analysed during the current study are not publicly available due to the level of personal information that is contained in the qualitative transcripts.Background: Diagnosis with Type 2 Diabetes is an opportunity for individuals to change their physical activity and dietary behaviours. Diabetes treatment guidelines recommend theory-based, patient-centred care and advocate the provision of support for patient motivation but the motivational experiences of people newly diagnosed with diabetes have not been well studied. Framed in self-determination theory, this study aimed to qualitatively explore how this patient group articulate and experience different types of motivation when attempting lifestyle change. Methods: A secondary analysis of semi-structured interview data collected with 30 (n female = 18, n male = 12) adults who had been newly diagnosed with type two diabetes and were participants in the Early ACTID trial was undertaken. Deductive directed content analysis was performed using NVivo V10 and researcher triangulation to identify and describe patient experiences and narratives that reflected the motivation types outlined in selfdetermination theory and if/how these changed over time. Results: The findings revealed the diversity in motivation quality both between and within individuals over time and that patients with newly-diagnosed diabetes have multifaceted often competing motivations for lifestyle behaviour change. Applying self-determination theory, we identified that many participants reported relatively dominant controlled motivation to comply with lifestyle recommendations, avoid their non-compliance being “found out” or supress guilt following lapses in behaviour change attempts. Such narratives were accompanied by experiences of frustrating slow behaviour change progress. More autonomous motivation was expressed as something often achieved over time and reflected goals to improve health, quality of life or family time. Motivational internalisation was evident and some participants had integrated their behaviour change to a new way of life which they found resilient to common barriers. Conclusions: Motivation for lifestyle change following diagnosis with type two diabetes is complex and can be relatively low in self-determination. To achieve the patient empowerment aspirations of current national health care plans, intervention developers, and clinicians would do well to consider the quality not just quantity of their patients’ motivation.National Institute for Health Research (NIHR

Accuracy Analysis of Interpolation Methods on Flash Glucose Monitoring Data

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordConference poster abstractDiabetes UK Professional Conference 2021, 19 - 30 April 2021, OnlineResearch Englan