One size does not fit all - stroke survivor's views on group self-management interventions

INTRODUCTION: Stroke is the main cause of complex disability in the UK. Many stroke survivors feel abandoned when rehabilitation ends and more than half are left with long-term unmet needs. There is now emerging interest in whether group self-management programs (SMP) specifically for stroke survivors could help. However, more work is required to understand the acceptability of group SMPs to stroke survivors and the factors of concern that could impact efficacy. PURPOSE: The purpose of this study is to explore stroke survivor's views on (1) possible benefits of a group SMP, (2) possible challenges of a group SMP, and (3) when/where to implement a SMP in an individual's stroke journey. METHOD: Fourteen stroke survivors took part in semi-structured interviews, which were analyzed using an inductive thematic approach. RESULTS: Three main themes were identified in the data: (1) a space to share support, (2) it is not a one size fits all problem, and (3) how is it all going to happen? CONCLUSION: A varied group of stroke survivors can provide valuable insight and ideas about how group SMP's should be constructed. To the best of our knowledge, this is the first patient engagement study that explores group SMPs for stroke. In future work, researchers may find it helpful to consider the findings from this study to inform the design of group SMPs. Implications for Rehabilitation There is interest in whether unmet needs after stroke could be addressed through a group self-management program (SMP). Stroke survivors can provide valuable insight and ideas about how group SMPs should be constructed. Group SMPs should carefully consider: how to create a safe space in which stroke survivors feel comfortable, the impact of the facilitators, tailoring the group to the individual, the presence of carers, and the emotional impact of a group SMP

Dyskeratosis Congenita links telomere attrition to age-related systemic energetics.

Underlying mechanisms of plasma metabolite signatures of human ageing and age-related diseases are not clear but telomere attrition and dysfunction are central to both. Dyskeratosis Congenita (DC) is associated with mutations in the telomerase enzyme complex (TERT, TERC, and DKC1) and progressive telomere attrition. We analyzed the effect of telomere attrition on senescence associated metabolites in fibroblast conditioned media and DC patient plasma. Samples were analyzed by gas chromatography/ mass spectrometry and liquid chromatography/ mass spectrometry. We showed extracellular citrate was repressed by canonical telomerase function in vitro and associated with DC leukocyte telomere attrition in vivo; leading to the hypothesis that altered citrate metabolism detects telomere dysfunction. However, elevated citrate and senescence factors only weakly distinguished DC patients from controls, whereas elevated levels of other tricarboxylic acid cycle metabolites, lactate and especially pyruvate distinguished them with high significance. The DC plasma signature most resembled that of patients with loss of function pyruvate dehydrogenase complex mutations and that of older subjects but significantly not those of type 2 diabetes, lactic acidosis, or elevated mitochondrial reactive oxygen species (1-3). Additionally, our data are consistent with further metabolism of citrate and lactate in the liver and kidneys. Citrate uptake in certain organs modulates age-related disease in mice and our data has similarities with age-related disease signatures in humans. Our results have implications for the role of telomere dysfunction in human ageing in addition to its early diagnosis and the monitoring of anti-senescence therapeutics, especially those designed to improve telomere function

CRISPR-Cas9 correction of a nonsense mutation in LCA5 rescues lebercilin expression and localization in human retinal organoids

Mutations in the lebercilin-encoding gene LCA5 cause one of the most severe forms of Leber congenital amaurosis, an early-onset retinal disease that results in severe visual impairment. Here, we report on the generation of a patient-specific cellular model to study LCA5-associated retinal disease. CRISPR-Cas9 technology was used to correct a homozygous nonsense variant in LCA5 (c.835C>T; p.Q279∗) in patient-derived induced pluripotent stem cells (iPSCs). The absence of off-target editing in gene-corrected (isogenic) control iPSCs was demonstrated by whole-genome sequencing. We differentiated the patient, gene-corrected, and unrelated control iPSCs into three-dimensional retina-like cells, so-called retinal organoids. We observed opsin and rhodopsin mislocalization to the outer nuclear layer in patient-derived but not in the gene-corrected or unrelated control organoids. We also confirmed the rescue of lebercilin expression and localization along the ciliary axoneme within the gene-corrected organoids. Here, we show the potential of combining precise single-nucleotide gene editing with the iPSC-derived retinal organoid system for the generation of a cellular model of early-onset retinal disease

Grouping practices in the primary school: what influences change?

During the 1990s, there was considerable emphasis on promoting particular kinds of pupil grouping as a means of raising educational standards. This survey of 2000 primary schools explored the extent to which schools had changed their grouping practices in responses to this, the nature of the changes made and the reasons for those changes. Forty eight percent of responding schools reported that they had made no change. Twenty two percent reported changes because of the literacy hour, 2% because of the numeracy hour, 7% because of a combination of these and 21% for other reasons. Important influences on decisions about the types of grouping adopted were related to pupil learning and differentiation, teaching, the implementation of the national literacy strategy, practical issues and school self-evaluation

Scallop swimming kinematics and muscle performance: modelling the effects of "within-animal" variation in temperature sensitivity

Escape behaviour was investigated in Queen scallops (Aequipecten opercularis) acclimated to 5, 10 or 15 degrees C and tested at their acclimation temperature. Scallops are active molluscs, able to escape from predators by jet-propelled swimming using a striated muscle working in opposition to an elastic hinge ligament. The first cycle of the escape response was recorded using high-speed video ( 250 Hz) and whole-animal velocity and acceleration determined. Muscle shortening velocity, force and power output were calculated using measurements of valve movement and jet area, and a simple biomechanical model. The average shortening speed of the adductor muscle had a Q(10) of 2.04, significantly reducing the duration of the jetting phase of the cycle with increased temperature. Muscle lengthening velocity and the overall duration of the clap cycle were changed little over the range 5 - 15 degrees C, as these parameters were controlled by the relatively temperature-insensitive, hinge ligament. Improvements in the average power output of the adductor muscle over the first clap cycle ( 222 vs. 139 W kg(-1) wet mass at 15 and 5 degrees C respectively) were not translated into proportional increases in overall swimming velocity, which was only 32% higher at 15 degrees C ( 0.37m s(-1)) than 5 degrees C (0.28 m s(-1))

The use of quantitative sensory testing in cancer pain assessment: A systematic review

Objective: To summarize the literature on the use of quantitative sensory testing (QST) in the assessment of pain in people with cancer and to describe which QST parameters consistently demonstrate abnormal sensory processing in patients with cancer pain. Databases and Data Treatment: Medline, EMBASE, AMED, CINAHL, SCOPUS and CENTRAL were searched for observational or experimental studies using QST in patients with a cancer diagnosis and reporting pain. Search strategies were based on the terms “quantitative sensory testing”, “cancer”, “pain”, “cancer pain” and “assessment”. Databases were searched from inception to January 2019. Data were extracted and synthesized narratively, structured around the different QST modalities and sub‐grouped by cancer pain aetiology (tumour‐ or treatment‐related pain). Results: Searches identified 286 records of which 18 met the eligibility criteria for inclusion. Three studies included patients with tumour‐related pain, and 15 studies included patients with pain from chemotherapy‐induced peripheral neuropathy (CIPN). Across all studies, 50% (9/18) reported sensory abnormities using thermal detection thresholds (cool and warm), 44% (8/18) reported abnormal mechanical detection thresholds using von‐Frey filaments and 39% (7/18) found abnormal pinprick thresholds. Abnormal vibration and thermal pain (heat/cold) thresholds were each reported in a third of included studies. Conclusion: This systematic review highlights the lack of published data characterizing the sensory phenotype of tumour‐related cancer pain. This has implications for our understanding of the underlying pathophysiological mechanisms of cancer pain. Understanding the multiple mechanisms driving cancer pain will help to move towards rational individualized analgesic treatment choices. Significance: This systematic review found that pain in cancer patients is associated with abnormal sensory responses to thermal, mechanical and pinprick stimuli. However, these findings are based primarily on studies of chemotherapy‐induced peripheral neuropathy and data on tumour‐related pain are lacking, warranting further research

Constraining noncommutative field theories with holography

An important window to quantum gravity phenomena in low energy noncommutative (NC) quantum field theories (QFTs) gets represented by a specific form of UV/IR mixing. Yet another important window to quantum gravity, a holography, manifests itself in effective QFTs as a distinct UV/IR connection. In matching these two principles, a useful relationship connecting the UV cutoff $\Lambda_{\rm UV}$, the IR cutoff $\Lambda_{\rm IR}$ and the scale of noncommutativity $\Lambda_{\rm NC}$, can be obtained. We show that an effective QFT endowed with both principles may not be capable to fit disparate experimental bounds simultaneously, like the muon $g-2$ and the masslessness of the photon. Also, the constraints from the muon $g-2$ preclude any possibility to observe the birefringence of the vacuum coming from objects at cosmological distances. On the other hand, in NC theories without the UV completion, where the perturbative aspect of the theory (obtained by truncating a power series in $\Lambda_{\rm NC}^{-2}$) becomes important, a heuristic estimate of the region where the perturbative expansion is well-defined $E/ \Lambda_{\rm NC} \lesssim 1$, gets affected when holography is applied by providing the energy of the system $E$ a $\Lambda_{\rm NC}$-dependent lower limit. This may affect models which try to infer the scale $\Lambda_{\rm NC}$ by using data from low-energy experiments.Comment: 4 pages, version to be published in JHE

Comparison of breast and bowel cancer screening uptake patterns in a common cohort of South Asian women in England

Background: Inequalities in uptake of cancer screening by ethnic minority populations are well documented in a number of international studies. However, most studies to date have explored screening uptake for a single cancer only. This paper compares breast and bowel cancer screening uptake for a cohort of South Asian women invited to undertake both, and similarly investigates these women's breast cancer screening behaviour over a period of fifteen years. Methods: Screening data for rounds 1, 2 and 5 (1989-2004) of the NHS breast cancer screening programme and for round 1 of the NHS bowel screening pilot (2000-2002) were obtained for women aged 50-69 resident in the English bowel screening pilot site, Coventry and Warwickshire, who had been invited to undertake breast and bowel cancer screening in the period 2000-2002. Breast and bowel cancer screening uptake levels were calculated and compared using the chi-squared test. Results: 72,566 women were invited to breast and bowel cancer screening after exclusions. Of these, 3,539 were South Asian and 69,027 non-Asian; 18,730 had been invited to mammography over the previous fifteen years (rounds 1 to 5). South Asian women were significantly less likely to undertake both breast and bowel cancer screening; 29.9% (n = 1,057) compared to 59.4% (n = 40,969) for non-Asians (p < 0.001). Women in both groups who consistently chose to undertake breast cancer screening in rounds 1, 2 and 5 were more likely to complete round 1 bowel cancer screening. However, the likelihood of completion of bowel cancer screening was still significantly lower for South Asians; 49.5% vs. 82.3% for non-Asians, p < 0.001. South Asian women who undertook breast cancer screening in only one round were no more likely to complete bowel cancer screening than those who decided against breast cancer screening in all three rounds. In contrast, similar women in the non-Asian population had an increased likelihood of completing the new bowel cancer screening test. The likelihood of continued uptake of mammography after undertaking screening in round 1 differed between South Asian religio-linguistic groups. Noticeably, women in the Muslim population were less likely to continue to participate in mammography than those in other South Asian groups. Conclusions: Culturally appropriate targeted interventions are required to reduce observed disparities in cancer screening uptakes

Using technology to deliver cancer follow-up : a systematic review

Peer reviewedPublisher PD