Qualitative findings from an exploratory trial of the Healthy Lifestyles Programme (HeLP) and their implications for the process evaluation in the definitive trial.

This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.Approximately one third of 10-11 year olds in England are now overweight or obese suggesting that population approaches are urgently required. However, despite the increasing number of school-based interventions to prevent obesity, results continue to be inconsistent and it is still unclear what the necessary conditions are that lead to the sustained behaviour change required to affect weight status. The Healthy Lifestyles Programme is a theoretically informed four phase multi-component intervention which seeks to create supportive school and home environments for healthy behaviours.National Institute for Health Research (NIHR) Research for Patient Benefit ProgrammeCollaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsul

Evaluating a radiotherapy deep learning synthetic CT algorithm for PET-MR attenuation correction in the pelvis

\ua9 2024, The Author(s). Background: Positron emission tomography–magnetic resonance (PET-MR) attenuation correction is challenging because the MR signal does not represent tissue density and conventional MR sequences cannot image bone. A novel zero echo time (ZTE) MR sequence has been previously developed which generates signal from cortical bone with images acquired in 65 s. This has been combined with a deep learning model to generate a synthetic computed tomography (sCT) for MR-only radiotherapy. This study aimed to evaluate this algorithm for PET-MR attenuation correction in the pelvis. Methods: Ten patients being treated with ano-rectal radiotherapy received a 18 F-FDG-PET-MR in the radiotherapy position. Attenuation maps were generated from ZTE-based sCT (sCTAC) and the standard vendor-supplied MRAC. The radiotherapy planning CT scan was rigidly registered and cropped to generate a gold standard attenuation map (CTAC). PET images were reconstructed using each attenuation map and compared for standard uptake value (SUV) measurement, automatic thresholded gross tumour volume (GTV) delineation and GTV metabolic parameter measurement. The last was assessed for clinical equivalence to CTAC using two one-sided paired t tests with a significance level corrected for multiple testing of p≤ 0.05 / 7 = 0.007 . Equivalence margins of \ub1 3.5 % were used. Results: Mean whole-image SUV differences were −0.02% (sCTAC) compared to −3.0% (MRAC), with larger differences in the bone regions (−0.5% to −16.3%). There was no difference in thresholded GTVs, with Dice similarity coefficients ≥ 0.987 . However, there were larger differences in GTV metabolic parameters. Mean differences to CTAC in SUV max were 1.0 \ub1 0.8 % (\ub1 standard error, sCTAC) and - 4.6 \ub1 0.9 % (MRAC), and 1.0 \ub1 0.7 % (sCTAC) and - 4.3 \ub1 0.8 % (MRAC) in SUV mean . The sCTAC was statistically equivalent to CTAC within a \ub1 3.5 % equivalence margin for SUV max and SUV mean (p= 0.007 and p= 0.002), whereas the MRAC was not (p= 0.88 and p= 0.83). Conclusion: Attenuation correction using this radiotherapy ZTE-based sCT algorithm was substantially more accurate than current MRAC methods with only a 40 s increase in MR acquisition time. This did not impact tumour delineation but did significantly improve the accuracy of whole-image and tumour SUV measurements, which were clinically equivalent to CTAC. This suggests PET images reconstructed with sCTAC would enable accurate quantitative PET images to be acquired on a PET-MR scanner

A qualitative evaluation of the impact of a Good Life Club on people living with dementia and care partners

Background: Research suggests there is a lack of post diagnostic support to enable people living with dementia to fulfil social and active lives throughout their dementia journey. Gardening has been found to have many benefits for people living with dementia. Although such research is important, most research frames people with dementia as passive recipients of stimulation. The impact of a community-based gardening group where people living with dementia are active in the development of an outdoor space is underdeveloped. Knowledge about the impact of participating in such groups is also sparse. The Good Life Club (GLC) was co-developed and evaluated to respond to these gaps. Objectives: The primary aim of this paper is to present the findings regarding the impact of attending the GLC on the self-reported wellbeing for people living with dementia and care partners. Methods: Qualitative data were collected via 22 semi-structured interviews. Fourteen interviews were conducted before the GLC and eight after the GLC. Thematic Analysis was used to analyse data. Dementia Care Mapping Data was collected to supplement the interview data. Findings: Four key themes were identified. The first was that participants considered having active participation in social life to be a key aspect of living a good life. The second was that the way the GLC was set up and delivered gave the participants ownership of the GLC and within this they felt able to contribute. The third was the importance of social connectedness and peer support to the wellbeing of both people living with dementia and care partners. Fourth, positive mood and wellbeing was directly experienced through gardening. Conclusions: The combination of long-term investment of time and energy to the GLC, on-going friendships and in-session autonomy, act as key ingredients in creating a group that is relaxed, full of humour and highly valued

The Healthy Lifestyles Programme (HeLP), a novel school-based intervention to prevent obesity in school children: study protocol for a randomised controlled trial

This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.Over the last three decades there has been a substantial increase in the proportion of children who are overweight or obese. The Healthy Lifestyles Programme (HeLP) is a novel school-based intervention, using highly interactive and creative delivery methods to prevent obesity in children.NIH

Resolving debris discs in the far-infrared: early highlights from the DEBRIS survey

We present results from the earliest observations of DEBRIS, a Herschel Key Programme to conduct a volume- and flux-limited survey for debris discs in A-type through M-type stars. PACS images (from chop/nod or scan-mode observations) at 100 and 160 micron are presented toward two A-type stars and one F-type star: beta Leo, beta UMa and eta Corvi. All three stars are known disc hosts. Herschel spatially resolves the dust emission around all three stars (marginally, in the case of beta UMa), providing new information about discs as close as 11 pc with sizes comparable to that of the Solar System. We have combined these data with existing flux density measurements of the discs to refine the SEDs and derive estimates of the fractional luminosities, temperatures and radii of the discs.Comment: to be published in A&A, 5 pages, 2 color figure

Simulation of Preterm Neonatal Brain Metabolism During Functional Neuronal Activation Using a Computational Model

We present a computational model of metabolism in the preterm neonatal brain. The model has the capacity to mimic haemodynamic and metabolic changes during functional activation and simulate functional near-infrared spectroscopy (fNIRS) data. As an initial test of the model's efficacy, we simulate data obtained from published studies investigating functional activity in preterm neonates. In addition we simulated recently collected data from preterm neonates during visual activation. The model is well able to predict the haemodynamic and metabolic changes from these observations. In particular, we found that changes in cerebral blood flow and blood pressure may account for the observed variability of the magnitude and sign of stimulus-evoked haemodynamic changes reported in preterm infants

Normative Alethic Pluralism

Some philosophers have argued that truth is a norm of judgement and have provided a variety of formulations of this general thesis. In this paper, I shall side with these philosophers and assume that truth is a norm of judgement. What I am primarily interested in here are two core questions concerning the judgement-truth norm: (i) what are the normative relationships between truth and judgement? And (ii) do these relationships vary or are they constant? I argue for a pluralist picture—what I call Normative Alethic Pluralism (NAP)—according to which (i) there is more than one correct judgement-truth norm and (ii) the normative relationships between truth and judgement vary in relation to the subject matter of the judgement. By means of a comparative analysis of disagreement in three areas of the evaluative domain—refined aesthetics, basic taste and morality—I show that there is an important variability in the normative significance of disagreement—I call this the variability conjecture. By presenting a variation of Lynch’s scope problem for alethic monism, I argue that a monistic approach to the normative function of truth is unable to vindicate the conjecture. I then argue that normative alethic pluralism provides us with a promising model to account for it

Anti-HIV-1 activity of cellulose acetate phthalate: Synergy with soluble CD4 and induction of "dead-end" gp41 six-helix bundles

BACKGROUND: Cellulose acetate phthalate (CAP), a promising candidate microbicide for prevention of sexual transmission of the human immunodeficiency virus type 1 (HIV-1) and other sexually transmitted disease (STD) pathogens, was shown to inactivate HIV-1 and to block the coreceptor binding site on the virus envelope glycoprotein gp120. It did not interfere with virus binding to CD4. Since CD4 is the primary cellular receptor for HIV-1, it was of interest to study CAP binding to HIV-1 complexes with soluble CD4 (sCD4) and its consequences, including changes in the conformation of the envelope glycoprotein gp41 within virus particles. METHODS: Enzyme-linked immunosorbent assays (ELISA) were used to study CAP binding to HIV-1-sCD4 complexes and to detect gp41 six-helix bundles accessible on virus particles using antibodies specific for the α-helical core domain of gp41. RESULTS: 1) Pretreatment of HIV-1 with sCD4 augments subsequent binding of CAP; 2) there is synergism between CAP and sCD4 for inhibition of HIV-1 infection; 3) treatment of HIV-1 with CAP induced the formation of gp41 six-helix bundles. CONCLUSIONS: CAP and sCD4 bind to distinct sites on HIV-1 IIIB and BaL virions and their simultaneous binding has profound effects on virus structure and infectivity. The formation of gp41 six-helical bundles, induced by CAP, is known to render the virus incompetent for fusion with target cells thus preventing infection

Trial baseline characteristics of a cluster randomised controlled trial of a school-located obesity prevention programme; the Healthy Lifestyles Programme (HeLP) trial

This is the final version of the article. Available from BioMed Central via the DOI in this record.Background We have developed a healthy lifestyles programme (HeLP) for primary school aged children (9–10 years), currently being evaluated in a definitive cluster randomised controlled trial. This paper descriptively presents the baseline characteristics of trial children (BMI, waist circumference, % body fat, diet and physical activity) by gender, cluster level socio-economic status, school size and time of recruitment into the trial. Methods Schools were recruited from across the South West of England and allocated 1:1 to either intervention (HeLP) or control (usual practice) stratified by the proportion of children eligible for free school meals (FSM, 1 Year 5 class). The primary outcome is change in body mass index standard deviation score (BMI sds) at 24 months post-randomisation. Secondary outcomes are BMI sds at 18 months, waist circumference and percentage body fat sds at 18 and 24 months, proportion of children classified as underweight, overweight and obese at 18 and 24 months, physical activity (for a sub-sample) and food intake at 18 months. Results At baseline 11.4% and 13.6% of children were categorised as overweight or obese respectively. A higher percentage of girls than boys (25.3% vs 24.8%) and children from schools in FSM category 2 (28.2% vs 23.2%) were overweight or obese. Children were consuming a mean (range) of 4.15 (0–13) energy dense snacks (EDS) and 3.23 (0–9) healthy snacks (HS) per day with children from schools in FSM category 2 consuming more EDS and negative food markers and less HS and positive food markers. Children spent an average 53.6 min per day (11.9 to 124.8) in MVPA and thirteen hours (779.3 min) per day (11 h to 15 h) doing less than ‘light’ intensity activity. Less than 5% of children achieved the Departments of Health’s recommendation of 60 min of MVPA every day. Conclusion We have excellent completeness of baseline data for all measures and have achieved compliance to accelerometry not seen before in other large scale studies. Our anthropometric baseline data is representative of local and national data for children this age and reflects the gender and socio-economic variations expected of children this age in relation to physical activity and weight status.The definitive trial of HeLP is funded by the UK National Institute for Health Research (NIHR) Public Health Research Programme (10/3010/01) and a full report will be published on the NIHR website. Intervention materials and delivery was funded by the Peninsula College of Medicine and Dentistry. PenCLAHRC provided methodological support during the transition from the exploratory trial to the definitive evaluation