Treatment of type 2 diabetes with antioxidant vitamin C therapy

High dose vitamin C supplementation significantly improved insulin sensitivity in skeletal muscle of people with type 2 diabetes. This clinically relevant improvement corresponded with improvements in vitamin C and oxidative stress levels in skeletal muscle. Vitamin C supplementation could be an effective adjunct therapy in people with type 2 diabetes

A bifurcation analysis of an open loop internal combustion engine

The process of engine mapping in the automotive industry identifies steady-state engine responses by running an engine at a given operating point (speed and load) until its output has settled. While the time simulating this process with a computational model for one set of parameters is relatively short, the cumulative time to map all possible combinations becomes computationally inefficient. This work presents an alternative method for mapping out the steady-state response of an engine in simulation by applying bifurcation theory. The bifurcation approach used in this work allows the engine's steady-state response to be traced through the model's state-parameter space under the simultaneous variation of one or more model parameters. To demonstrate this approach, a bifurcation analysis of a simplified nonlinear engine model is presented. Using "throttle position" and "desired load torque signal", the engine's dynamic response is classified into distinct regions bounded by bifurcation points. These bifurcations are shown to correspond to key physical properties of the open-loop system: fold bifurcations correspond to the minimum throttle angle required for a steady-state engine response; Hopf bifurcations bound a region where self-sustaining oscillations occur. The techniques used in this case study demonstrate the efficiency a bifurcation approach has at highlighting different regions of dynamic behavior in the engine's state-parameter space. Such an approach could speed up the mapping process and enhance the automotive engineer's understanding of an engine's underlying dynamic behavior. The information obtained from the bifurcation analysis could also be used to inform the design of future engine control strategies

Cost consequence analysis of transcutaneous tibial nerve stimulation (TTNS) for urinary incontinence in care home residents alongside a randomised controlled trial

Background: Urinary incontinence (UI) is prevalent in more than half of residents of nursing and residential care homes and can have a detrimental impact on dignity and quality of life. Care homes predominantly use absorbent pads to contain UI rather than actively treat the condition. Transcutaneous tibial nerve stimulation (TTNS) is a non-invasive, safe, low-cost intervention with demonstrated effectiveness for reducing UI in adults. We examined the costs and consequences of delivering TTNS to care home residents in comparison to sham (inactive) electrical stimulation.Methods: A cost consequence analysis approach was used to assemble and present the resource use and outcome data for the ELECTRIC trial which randomised 406 residents with UI from 37 care homes in the United Kingdom to receive 12 sessions of 30 minutes of either TTNS or sham (inactive) TTNS. TTNS was administered by care home staff over 6 weeks. Health state utility was measured using DEMQOL-U and DEMQOL-PROXY-U at baseline, 6 weeks and 18 weeks follow-up. Staff completed a resource use questionnaire at baseline, 6 weeks and 18 weeks follow-up, which also assessed use of absorbent pads. Results: HRQoL did not change significantly in either randomised group. Delivery of TTNS was estimated to cost £81.20 per participant, plus training and support costs of £121.03 per staff member. 85% of participants needed toilet assistance as routine, on average requiring one or two staff members to be involved 4 or 5 times in each 24 hours. Daily use of mobility aids and other assistive devices to use the toilet were reported. The value of staff time to assist residents to use the toilet (assuming an average of 5 minutes per resident per visit) was estimated as £19.17 (SD 13.22) for TTNS and £17.30 (SD 13.33) for sham (per resident in a 24-hour period).Conclusions: Use of TTNS to treat UI in care home residents did not lead to changes in resource use, particularly any reduction in the use of absorbent pads and no cost benefits for TTNS were shown. Managing continence in care homes is labour intensive, requiring both high levels of staff time and use of equipment aids

The feasibility and acceptability of trial procedures for a pragmatic randomised controlled trial of a structured physical activity intervention for people diagnosed with colorectal cancer: findings from a pilot trial of cardiac rehabilitation versus usual care (no rehabilitation) with an embedded qualitative study.

Background: Pilot and feasibility work is conducted to evaluate the operational feasibility and acceptability of the intervention itself and the feasibility and acceptability of a trials’ protocol design. The Cardiac Rehabilitation In Bowel cancer (CRIB) study was a pilot randomised controlled trial (RCT) of cardiac rehabilitation versus usual care (no rehabilitation) for post-surgical colorectal cancer patients. A key aim of the pilot trial was to test the feasibility and acceptability of the protocol design.Methods: A pilot RCT with embedded qualitative work was conducted in three sites. Participants were randomly allocated to cardiac rehabilitation or usual care groups. Outcomes used to assess the feasibility and acceptability of key trial parameters were screening, eligibility, consent, randomisation, adverse events, retention, completion, missing data, and intervention adherence rates. Colorectal patients’ and clinicians’ perceptions and experiences ofthe main trial procedures were explored by interview.Results: Quantitative study. Three sites were involved. Screening, eligibility, consent, and retention rates were 79 % (156/198), 67 % (133/198), 31 % (41/133), and 93 % (38/41), respectively. Questionnaire completion rates were 97. 5 % (40/41), 75 % (31/41), and 61 % (25/41) at baseline, follow-up 1, and follow-up 2, respectively. Sixty-nine percent (40) of accelerometer datasets were collected from participants; 31 % (20) were removed for not meetingwear-time validation.Qualitative study: Thirty-eight patients and eight clinicians participated. Key themes were benefits for people with colorectal cancer attending cardiac rehabilitation, barriers for people with colorectal cancer attending cardiac rehabilitation, generic versus disease-specific rehabilitation, key concerns about including people with cancer incardiac rehabilitation, and barriers to involvement in a study about cardiac rehabilitation.Conclusions: The study highlights where threats to internal and external validity are likely to arise in any future studies ofsimilar structured physical activity interventions for colorectal cancer patients using similar methods being conducted in similar contexts. This study shows that there is likely to be potential recruitment bias and potential imprecision due to sub-optimal completion of outcome measures, missing data, and sub-optimal intervention adherence. Hence, strategies to manage these risks should be developed to stack the odds in favour of conducting successful future trials

Hierarchical Level of Detail Optimisation for Constant Framerate Rendering of Radiosity Scenes

The predictive hierarchical level of detail optimization algorithm of Mason and Blake is experimentally evaluated in the form of a practical application to hierarchical radiosity. In a novel approach the recursively subdivided patch hierarchy generated by a perceptually refined hierarchical radiosity algorithm is treated as a hierarchical level of detail scene description. In this way we use the Mason-Blake algorithm to successfully maintain constant frame rates during the interactive rendering of the radiosity-generated scene. We establish that the algorithm is capable of maintaining uniform frame rendering times, but that the execution time of the optimization algorithm itself is significant and is strongly dependent on frame-to-frame coherence and the granularity of the level of detail description. To compensate we develop techniques which effectively reduce and limit the algorithm execution time: We restrict the execution times of the algorithm to guard against pathological situations and propose simplification transforms that increase the granularity of the scene description, at minimal cost to visual quality. We demonstrate that using these techniques the algorithm is capable of maintaining interactive frame rates for scenes of arbitrary complexity. Furthermore we provide guidelines for the appropriate use of predictive level of detail optimization algorithms derived from our practical experience

Abdominal massage plus advice, compared with advice only, for neurogenic bowel dysfunction in MS:a RCT

This project was funded by the National Institute for Health Research Health TechnologyPeer reviewedPublisher PD

Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress

A functional genomics study revealed that the activity of acetyl-CoA synthetase 2 (ACSS2) contributes to cancer cell growth under low-oxygen and lipid-depleted conditions. Comparative metabolomics and lipidomics demonstrated that acetate is used as a nutritional source by cancer cells in an ACSS2-dependent manner, and supplied a significant fraction of the carbon within the fatty acid and phospholipid pools. ACSS2 expression is upregulated under metabolically stressed conditions and ACSS2 silencing reduced the growth of tumor xenografts. ACSS2 exhibits copy-number gain in human breast tumors, and ACSS2 expression correlates with disease progression. These results signify a critical role for acetate consumption in the production of lipid biomass within the harsh tumor microenvironment

Estradiol-independent restoration of T-cell function in post-reproductive females

Aging leads to a general decline in protective immunity. The most common age-associated effects are in seen T-cell mediated immune function. Adult mice whose immune systems show only moderate changes in T-cell subsets tend to live longer than age-matched siblings that display extensive T-cell subset aging. Importantly, at the time of reproductive decline, the increase in disease risks in women significantly outpace those of men. In female mice, there is a significant decline in central and peripheral naïve T-cell subsets at the time of reproductive failure. Available evidence indicates that this naïve T-cell decline is sensitive to ovarian function and can be reversed in post-reproductive females by transplantation of young ovaries. The restoration of naïve T-cell subsets due to ovarian transplantation was impressive compared with post-reproductive control mice, but represented only a partial recovery of what was lost from 6 months of age. Apparently, the influence of ovarian function on immune function may be an indirect effect, likely moderated by other physiological functions. Estradiol is significantly reduced in post-reproductive females, but was not increased in post-reproductive females that received new ovaries, suggesting an estradiol-independent, but ovarian-dependent influence on immune function. Further evidence for an estradiol-independent influence includes the restoration of immune function through the transplantation of young ovaries depleted of follicles and through the injection of isolated ovarian somatic cells into the senescent ovaries of old mice. While the restoration of naïve T-cell populations represents only a small part of the immune system, the ability to reverse this important functional parameter independent of estradiol may hold promise for the improvement of post-reproductive female immune health. Further studies of the non-reproductive influence of the ovary will be needed to elucidate the mechanisms of the relationship between the ovary and health

CRIB—the use of cardiac rehabilitation services to aid the recovery of patients with bowel cancer: a pilot randomised controlled trial (RCT) with embedded feasibility study

Introduction: Patients with colorectal cancer report ongoing physical and psychological impairments and a high proportion of these patients are overweight, insufficiently active and high-risk drinkers, putting them at risk of poor recovery and risk of recurrence and comorbidities. A challenge is implementing sustainable and effective rehabilitation as part of routine care for this group.Methods and analysis: A two-arm pilot randomised controlled trial (RCT) with embedded feasibility study undertaken as a phased programme of work. The intervention involves an existing cardiac rehabilitation programme for cardiac patients accepting colorectal cancer patient referrals. The intervention consists of supervised exercise sessions run by a cardiac physiotherapist and information sessions. Phase 1 will involve one research site enrolling 12 patients to assess intervention and study design processes. Semistructured interviews with patients with colorectal cancer and cardiac patients and clinicians will be used to gather data on acceptability of the intervention and study procedures. Phase 2 will involve three sites enrolling 66 patients with colorectal cancer randomised to control or intervention groups. Outcome measures will be taken preintervention and postintervention, for phases 1 and 2. The primary outcome is accelerometer measured physical activity; secondary outcomes are self-report physical activity, quality of life, anxiety, depression, symptoms including fatigue. The following variables will also be examined to determine if these factors influence adherence and outcomes: self-efficacy, risk perception and treatments.Ethics and dissemination: Full ethical approval was granted by NRES Committees—North of Scotland (13/NS/0004; IRAS project ID: 121757) on 22 February 2013. The proposed work is novel in that it aims to test the feasibility and acceptability of using an evidence-based and theory driven existing cardiac rehabilitation service with patients with colorectal cancer. Should this model of rehabilitation prove to be clinically and cost effective we aim to conduct a randomised controlled trial of this intervention to measure effectiveness.Trial registration reference ISRCTN63510637; UKCRN id 14092