Reducing the Social Gradient in Uptake of the NHS Colorectal Cancer Screening Programme Using a Narrative-Based Information Leaflet: A Cluster-Randomised Trial

Objective: To test the effectiveness of adding a narrative leaflet to the current information material delivered by the NHS English colorectal cancer (CRC) screening programme on reducing socioeconomic inequalities in uptake. / Participants: 150,417 adults (59-74 years) routinely invited to complete the guaiac Faecal Occult Blood test (gFOBt) in March 2013. / Design: A cluster randomised controlled trial (ISRCTN74121020) to compare uptake between two arms. The control arm received the standard NHS CRC screening information material (SI) and the intervention arm received the standard information plus a supplementary narrative leaflet, which had previously been shown to increase screening intentions (SI+N). Between group comparisons were made for uptake overall and across socioeconomic status (SES). Results: Uptake was 57.7% and did not differ significantly between the two trial arms (SI: 58.5%; SI+N: 56.7%; Odds Ratio = 0.93, 95% confidence interval: 0.81-1.06, p = 0.27). There was no interaction between group and SES quintile (p = 0.44). / Conclusions: Adding a narrative leaflet to existing information materials does not reduce the SES gradient in uptake. Despite the benefits of using a pragmatic trial design, the need to add to, rather than replace existing information may have limited the true value of an evidence-based intervention on behaviour

Impact of general practice endorsement on the social gradient in uptake in bowel cancer screening

This is a summary of independent research funded by the National Institute for Health. Research (NIHR)’s Programme Grants for Applied Research Programme (RP-PG-0609–10106

Biogeography of Mentzelia thompsonii and related species (Loasaceae).

Mentzelia thompsonii is the only species in Mentzelia section Trachyphytum endemic to the Colorado Plateau and one of only a few that do not occur in California. In order to investigate the geographic origins, ecological function, and evolutionary potential of M. thompsonii and related species, we combine evidence from DNA, soil chemistry, and environmental niche modeling in a phylogenetic context. Based on ndhF–rpl32 cpDNA sequences from 185 specimens of M. thompsonii and 42 specimens representing the remaining 21 species in section Trachyphytum, we found that M. thompsonii is monophyletic and phylogenetically isolated from other species in Trachyphytum, suggesting that it is a paleoendemic. In contrast, the South American species, M. solierii, was placed sister to a haplotype from M. packardiae, representing the first published phylogenetic investigation of M. solierii. Soil analyses from all North American species in section Trachyphytum show that the edaphic niche of M. thompsonii is significantly different, and niche modeling with MaxEnt found that the distribution of Mancos Shale outcrops was five times more important than the most important climate variable for predicting the distribution of M. thompsonii. Surprisingly, subrange haplotype diversity in M. thompsonii did not match niche projections of climatic refugia during the last glacial maximum. Instead, diversity was lowest in the southernmost subrange and highest in the northernmost subrange of M. thompsonii. However, haplotype diversity was congruent with the projected distribution of M. thompsonii in 2081–2100, suggesting that genetic diversity in M. thompsonii has been shaped more by rapid warming and drought during interglacial periods than by the gradual cooling leading into glacial periods

Repetitive task training for improving functional ability after stroke

Background Repetitive task training (RTT) involves the active practice of task-specific motor activities and is a component of current therapy approaches in stroke rehabilitation. Objectives Primary objective: To determine if RTT improves upper limb function/reach and lower limb function/balance in adults after stroke. Secondary objectives: 1) To determine the effect of RTT on secondary outcome measures including activities of daily living, global motor function, quality of life/health status and adverse events. 2) To determine the factors that could influence primary and secondary outcome measures, including the effect of 'dose' of task practice; type of task (whole therapy, mixed or single task); timing of the intervention and type of intervention. Search methods We searched the Cochrane Stroke Group Trials Register (4 March 2016); the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 5: 1 October 2006 to 24 June 2016); MEDLINE (1 October 2006 to 8 March 2016); Embase (1 October 2006 to 8 March 2016); CINAHL (2006 to 23 June 2016); AMED (2006 to 21 June 2016) and SPORTSDiscus (2006 to 21 June 2016). Selection criteria Randomised/quasi-randomised trials in adults after stroke, where the intervention was an active motor sequence performed repetitively within a single training session, aimed towards a clear functional goal. Data collection and analysis Two review authors independently screened abstracts, extracted data and appraised trials. We determined the quality of evidence within each study and outcome group using the Cochrane 'Risk of bias' tool and GRADE (Grades of Recommendation, Assessment, Development and Evaluation) criteria. We did not assess follow-up outcome data using GRADE. We contacted trial authors for additional information. Main results We included 33 trials with 36 intervention-control pairs and 1853 participants. The risk of bias present in many studies was unclear due to poor reporting; the evidence has therefore been rated 'moderate' or 'low' when using the GRADE system. There is low-quality evidence that RTT improves arm function (standardised mean difference (SMD) 0.25, 95% confidence interval (CI) 0.01 to 0.49; 11 studies, number of participants analysed = 749), hand function (SMD 0.25, 95% CI 0.00 to 0.51; eight studies, number of participants analysed = 619), and lower limb functional measures (SMD 0.29, 95% CI 0.10 to 0.48; five trials, number of participants analysed = 419). There is moderate-quality evidence that RTT improves walking distance (mean difference (MD) 34.80, 95% CI 18.19 to 51.41; nine studies, number of participants analysed = 610) and functional ambulation (SMD 0.35, 95% CI 0.04 to 0.66; eight studies, number of participants analysed = 525). We found significant differences between groups for both upper-limb (SMD 0.92, 95% CI 0.58 to 1.26; three studies, number of participants analysed = 153) and lower-limb (SMD 0.34, 95% CI 0.16 to 0.52; eight studies, number of participants analysed = 471) outcomes up to six months post treatment but not after six months. Effects were not modified by intervention type, dosage of task practice or time since stroke for upper or lower limb. There was insufficient evidence to be certain about the risk of adverse events. Authors' conclusions There is low- to moderate-quality evidence that RTT improves upper and lower limb function; improvements were sustained up to six months post treatment. Further research should focus on the type and amount of training, including ways of measuring the number of repetitions actually performed by participants. The definition of RTT will need revisiting prior to further updates of this review in order to ensure it remains clinically meaningful and distinguishable from other interventions

Design and characterization of the POLARBEAR-2b and POLARBEAR-2c cosmic microwave background cryogenic receivers

The POLARBEAR-2/Simons Array Cosmic Microwave Background (CMB) polarization experiment is an upgrade and expansion of the existing POLARBEAR-1 (PB-1) experiment, located in the Atacama desert in Chile. Along with the CMB temperature and $E$-mode polarization anisotropies, PB-1 and the Simons Array study the CMB $B$-mode polarization anisotropies produced at large angular scales by inflationary gravitational waves, and at small angular scales by gravitational lensing. These measurements provide constraints on various cosmological and particle physics parameters, such as the tensor-to-scalar ratio $r$, and the sum of the neutrino masses. The Simons Array consists of three 3.5 m diameter telescopes with upgraded POLARBEAR-2 (PB-2) cryogenic receivers, named PB-2a, -2b, and -2c. PB-2a and -2b will observe the CMB over multiple bands centered at 95 GHz and 150 GHz, while PB-2c will observe at 220 GHz and 270 GHz, which will enable enhanced foreground separation and de-lensing. Each Simons Array receiver consists of two cryostats which share the same vacuum space: an optics tube containing the cold reimaging lenses and Lyot stop, infrared-blocking filters, and cryogenic half-wave plate; and a backend which contains the focal plane detector array, cold readout components, and millikelvin refrigerator. Each PB-2 focal plane array is comprised of 7,588 dual-polarization, multi-chroic, lenslet- and antenna-coupled, Transition Edge Sensor (TES) bolometers which are cooled to 250 mK and read out using Superconducting Quantum Interference Devices (SQUIDs) through a digital frequency division multiplexing scheme with a multiplexing factor of 40. In this work we describe progress towards commissioning the PB-2b and -2c receivers including cryogenic design, characterization, and performance of both the PB-2b and -2c backend cryostats.Comment: 20 page

Protocol for the process evaluation of the Promoting Activity, Independence and stability in early Dementia (PrAISED), following changes required by the COVID-19 pandemic

Introduction. The PrAISED Randomised Controlled Trial (RCT) is evaluating a home-based, face-to-face, individually tailored, activity and exercise programme for people living with dementia. Social distancing requirements following the COVID-19 pandemic necessitated rapid changes to intervention delivery. Methods and analysis. A mixed methods process evaluation will investigate how the changes were implemented and the impact that these have on participants’ experience. An implementation study will investigate how the intervention was delivered during the pandemic. A study on the mechanisms of impact and context will investigate how these changes were experienced by the PrAISED participants, their carers and the therapists delivering the intervention. The study will commence in May 2020. Ethics and dissemination. The PrAISED RCT and process evaluation have received ethical approval number 18/YH/0059. The ISRCTN Registration Number for PrAISED is 15320670. The PrAISED process evaluation will enable us to understand how distancing and isolation affected participants, their activity and exercise routines, and whether the therapy programme could be continued with remote support. This will be valuable both in explaining trial results, and also contribute to understanding and designing new ways of delivering home-based services and rehabilitation interventions for people with dementia and their carers

The Impact of a Dementia-Friendly Exercise Class on People Living with Dementia: A Mixed-Methods Study

Exercise has multiple benefits for people living with dementia. A programme of group exercise classes for people with dementia and their family carers has been established in a University sports centre. This study aims to explore the impact of this programme on participants with dementia and their carers. A mixed-methods design including a prospective, repeated measures cohort study followed by focus groups was employed. Physiological and cognitive outcome measures were repeated at baseline and three months in a cohort of people with dementia attending a group exercise class. Focus groups on the participants’ experiences and their perceptions of the impact of the exercise class on their lives were then conducted. The results were analysed and mapped on a model, to illustrate the components that most likely promote participation. Sixteen participants (n = 8 with dementia, and n = 8 carers) were recruited, and completed both baseline and follow up assessments. Positive mean differences were found in physical activity (4.44), loneliness (1.75), mood (1.33) and cognition (1.13). Ten participants were included in the focus groups, which found that accessibility of the exercise venue, opportunities for socialisation and staff who were experienced working with people living with dementia were key to participants reporting benefits. The four key themes from the focus group data were synthesised to produce a model outlining the components that might generate a positive impact of the exercise classes and promote participation. Exercise classes for people with dementia can be delivered with success in novel environments such as University sports centres. There is some indication of improvement over a short period of time. The model derived from this study will inform strategies to promote attendance at dementia-friendly exercise classes

The facilitators and barriers to improving functional activity and wellbeing in people with dementia: a qualitative study from the process evaluation of Promoting Activity, Independence and Stability in Early Dementia (PrAISED)

BACKGROUND: The PRomoting Activity, Independence and Stability in Early Dementia (PrAISED) study delivered an exercise and functional activity programme to participants living with dementia. A Randomised Controlled Trial showed no measurable benefits in activities of daily living, physical activity or quality of life. OBJECTIVE: To explore participants' responses to PrAISED and explain why an intervention that might be expected to have produced measurable health gains did not do so. METHODS: A process evaluation using qualitative methods, comprising interviews and researcher notes. SETTING: Data were collected in participants' homes or remotely by telephone or videoconferencing. SAMPLE: A total of 88 interviews were conducted with 44 participants living with dementia (n = 32 intervention group; n = 12 control group) and 39 caregivers. A total of 69 interviews were conducted with 26 therapists. RESULTS: Participants valued the intervention as proactively addressing health issues that were of concern to them, and as a source of social contact, interaction, information and advice. Facilitators to achieving positive outcomes included perceiving progress towards desired goals, positive expectations, therapists' skills and rapport with participants, and caregiver support. Barriers included: cognitive impairment, which prevented independent engagement and carry-over between sessions; chronic physical health problems and intercurrent acute illness and injury; 'tapering' (progressively infrequent supervision intended to help develop habits and independent activity); and the COVID-19 pandemic. CONCLUSIONS: Self-directed interventions may not be appropriate in the context of dementia, even in the mild stages of the condition. Dementia-specific factors affected outcomes including caregiver support, rapport with therapists, availability of supervision, motivational factors and the limitations of remote delivery. The effects of cognitive impairment, multimorbidity and frailty overwhelmed any positive impact of the intervention. Maintenance of functional ability is valued, but in the face of inevitable progression of disease, other less tangible outcomes become important, challenging how we frame 'health gain' and trial outcomes

A critical role for endocytosis in Wnt signaling

BACKGROUND: The Wnt signaling pathway regulates many processes during embryonic development, including axis specification, organogenesis, angiogenesis, and stem cell proliferation. Wnt signaling has also been implicated in a number of cancers, bone density maintenance, and neurological conditions during adulthood. While numerous Wnts, their cognate receptors of the Frizzled and Arrow/LRP5/6 families and downstream pathway components have been identified, little is known about the initial events occurring directly after receptor activation. RESULTS: We show here that Wnt proteins are rapidly endocytosed by a clathrin- and dynamin-mediated process. While endocytosis has traditionally been considered a principal mechanism for receptor down-regulation and termination of signaling pathways, we demonstrate that interfering with clathrin-mediated endocytosis actually blocks Wnt signaling at the level of β-catenin accumulation and target gene expression. CONCLUSION: A necessary component of Wnt signaling occurs in a subcellular compartment distinct from the plasma membrane. Moreover, as internalized Wnts transit partially through the transferrin recycling pathway, it is possible that a "signaling endosome" serves as a nexus for activated Wnt pathway components

Tele-Rehabilitation for People with Dementia during the COVID-19 Pandemic: A Case-Study from England

ntroduction: The Promoting Activity, Independence and Stability in Early Dementia (PrAISED) is delivering an exercise programme for people with dementia. The Lincolnshire part�nership National Health Service (NHS) foundation Trust successfully delivered PrAISED through a video-calling platform during the Coronavirus Disease 2019 (COVID-19) pandemic. Methods: This qualitative case-study aimed to identify participants that video delivery worked for, to highlight its benefits and its challenges. Interviews were conducted between May and August 2020 with five participants with dementia and their caregivers (n = 10), as well as five therapists from the Lincolnshire partnership NHS foundation Trust. The interviews were analysed through thematic analysis. Results: Video delivery worked best when participants had a supporting caregiver and when therapists showed enthusiasm and had an established rapport with the client. Benefits included time efficiency of sessions, enhancing participants’ motivation, caregivers’ dementia awareness, and therapists’ creativity. Limitations included users’ poor IT skills and resources. Discussion: The COVID-19 pandemic required innovative ways of delivering rehabilitation. This study supports that people with dementia can use tele-rehabilitation, but success is reliant on having a caregiver and an enthusiastic and known therapis