Beyond design review: collaborating to create well-designed places in Scotland

This practice paper reflects on the national design advice service in Scotland that has been operated by Architecture & Design Scotland (A&DS) since 2005. Placed in the context of research on design review practice, the paper describes how design review in Scotland has evolved from a traditional panel model operating alongside a range of training and skills development functions into a more holistic and dynamic design advice service. The paper argues that the evolution of design review in Scotland signifies an innovative shift away from the often combative setting of a design panel, where the force of an argument frequently wins the day, towards a more measured, iterative and collaborative process of nurturing and enabling well-designed buildings and places

Impact of Tail Loss on the Behaviour and Locomotor Performance of Two Sympatric Lampropholis Skink Species

Caudal autotomy is an anti-predator behaviour that is used by many lizard species. Although there is an immediate survival benefit, the subsequent absence of the tail may inhibit locomotor performance, alter activity and habitat use, and increase the individuals' susceptibility to future predation attempts. We used laboratory experiments to examine the impact of tail autotomy on locomotor performance, activity and basking site selection in two lizard species, the delicate skink (Lampropholis delicata) and garden skink (L. guichenoti), that occur sympatrically throughout southeastern Australia and are exposed to an identical suite of potential predators. Post-autotomy tail movement did not differ between the two Lampropholis species, although a positive relationship between the shed tail length and distance moved, but not the duration of movement, was observed. Tail autotomy resulted in a substantial decrease in sprint speed in both species (28–39%), although this impact was limited to the optimal performance temperature (30°C). Although L. delicata was more active than L. guichenoti, tail autotomy resulted in decreased activity in both species. Sheltered basking sites were preferred over open sites by both Lampropholis species, although this preference was stronger in L. delicata. Caudal autotomy did not alter the basking site preferences of either species. Thus, both Lampropholis species had similar behavioural responses to autotomy. Our study also indicates that the impact of tail loss on locomotor performance may be temperature-dependent and highlights that future studies should be conducted over a broad thermal range

Temporal repeatability of behaviour in a lizard: implications for behavioural syndrome studies

It is well established that, across taxa, individuals within populations exhibit consistent differences in their behaviour across time and/or contexts. Further, the functional coupling of traits may result in the formation of a behavioural syndrome. Despite extensive evidence on the existence of consistent among-individual differences in behaviour and behavioural syndromes in the animal realm, these findings are predominately based upon short-term assessments, leading to questions regarding their stability over longer periods. Understanding if these estimates are temporally stable would allow predictions of individual behaviour to be made using short-term repeated measures. Here, we used 57 adult male delicate skinks (Lampropholis delicata) to evaluate the stability of behavioural variation observed both among (animal personality and behavioural plasticity) and within individuals (behavioural predictability), as well as behavioural syndromes, across short (four weeks) and long (five months) timeframes. To do so, we repeatedly assayed activity, exploration, and boldness five times per each individual. Overall, our study revealed complex patterns of behavioural variation and trait (co)variation over time. Activity was always repeatable across time intervals, whereas behavioural differences among individuals in exploration and boldness were not consistent. Yet a behavioural syndrome between activity and exploration was detected at both shorter and longer temporal scales, suggesting that syndrome structure in these traits does not vary as a function of time. Our findings indicate that, at least for some traits (e.g. activity) and studies, short-term measures may be adequate in serving as a proxy for long-term variation in individual behaviour, and to reveal the existence of behavioural syndromes at the population level

Perioperative supplementation with a fruit and vegetable juice powder concentrate and postsurgical morbidity: a double-blind, randomised, placebo controlled clinical trial

Aims Surgical trauma leads to an inflammatory response that causes surgical morbidity. Reduced antioxidant micronutrient (AM)a levels and/or excessive levels of Reactive Oxygen Species (ROS)b have previously been linked to delayed wound healing and presence of chronic wounds. We aimed to evaluate the effect of pre-operative supplementation with encapsulated fruit and vegetable juice powder concentrate (JuicePlus+®) on postoperative morbidity and Quality of Life (QoL)c. Methods We conducted a randomised, double-blind, placebo-controlled two-arm parallel clinical trial evaluating postoperative morbidity following lower third molar surgery. Patients aged between 18 and 65 years were randomised to take verum or placebo for 10 weeks prior to surgery and during the first postoperative week. The primary endpoint was the between-group difference in QoL over the first postoperative week, with secondary endpoints being related to other measures of postoperative morbidity (pain and trismus). Results One-hundred and eighty-three out of 238 randomised patients received surgery (Intention-To-Treat population). Postoperative QoL tended to be higher in the active compared to the placebo group (p=0.059). Furthermore, reduction in mouth opening 2 days after surgery was 3.1 mm smaller (p=0.042), the mean pain score over the postoperative week was 9.4 mm lower (p=0.007) and patients were less likely to experience moderate to severe pain on postoperative day 2 (RR 0.58, p=0.030), comparing verum to placebo groups. Conclusion Pre-operative supplementation with a fruit and vegetable supplement rich in AM may improve postoperative QoL and reduce surgical morbidity and post-operative complications after surgery

Oncometabolite induced primary cilia loss in pheochromocytoma

Primary cilia are sensory organelles involved in regulation of cellular signaling. Cilia loss is frequently observed in tumors; yet, the responsible mechanisms and consequences for tumorigenesis remain unclear. We demonstrate that cilia structure and function is disrupted in human pheochromocytomas – endocrine tumors of the adrenal medulla. This is concomitant with transcriptional changes within cilia-mediated signaling pathways that are associated with tumorigenesis generally and pheochromocytomas specifically. Importantly, cilia loss was most dramatic in patients with germline mutations in the pseudohypoxia-linked genes SDHx and VHL. Using a pheochromocytoma cell line derived from rat, we show that hypoxia and oncometabolite-induced pseudohypoxia are key drivers of cilia loss and identify that this is dependent on activation of an Aurora-A/HDAC6 cilia resorption pathway. We also show cilia loss drives dramatic transcriptional changes associated with proliferation and tumorigenesis. Our data provide evidence for primary cilia dysfunction contributing to pathogenesis of pheochromocytoma by a hypoxic/pseudohypoxic mechanism and implicates oncometabolites as ciliary regulators. This is important as pheochromocytomas can cause mortality by mechanisms including catecholamine production and malignant transformation, while hypoxia is a general feature of solid tumors. Moreover, pseudohypoxia-induced cilia resorption can be pharmacologically inhibited, suggesting potential for therapeutic intervention

Alternative job search strategies in remote rural and peri-urban labour markets: the role of social networks

This paper examines the importance of informal methods (especially social networking) to the job search strategies used by unemployed people. It compares three areas: a small rural town; a larger, more sparsely populated, remote rural area; and a centrally-located, peri-urban labour market. The analysis is based first on survey research undertaken with 490 job seekers across the study areas. Emerging issues were then followed up during a series of twelve focus groups. The survey research showed that job seekers in the rural study areas were significantly more likely to use social networks to look for work. However, those who had experienced repeated or long-term periods out of work, the unskilled and young people were significantly less likely to use such networks. Focus groups confirmed the perceived importance of social networking to the job search process in rural areas, in contrast to the more marginal role such methods appear to play in peri-urban settings. For many rural job seekers, formal job search activities conducted through Jobcentres were seen as largely symbolic, lacking the practical value of social networking. These results suggest that service providers seeking to assist unemployed people in rural areas need to address the problems faced by many disadvantaged job seekers who are currently caught between their lack of social network relations and the absence of local public employment service facilities in more remote communities

Attitudes towards Oral Health in Patients with Rheumatoid Arthritis: A Qualitative Study Nested within a Randomized Controlled Trial

Introduction: Patients with rheumatoid arthritis (RA) present a higher incidence and severity of periodontitis than the general population. Our study, Outcomes of Periodontal Treatment in Patients with Rheumatoid Arthritis (OPERA), was a randomized waiting-list controlled trial using mixed methods. Patients randomized to the intervention arm received intensive periodontal treatment, and those in the control arm received the same treatment with a 6-mo delay. Aim: The nested qualitative component aimed to explore patients’ experiences and priorities concerning oral health and barriers and facilitators for trial participation. Methods: Using purposive sampling until thematic saturation was reached, we conducted 21 one-to-one semistructured interviews with randomized patients in either of the 2 treatment arms as well as with patients who did not consent for trial participation. Results: The patients described their experiences about RA, oral health, and study participation. Previous experiences with dental care professionals shaped patients’ current perceptions about oral health and the place of oral health on their list of priorities compared with other conditions. Patients also highlighted some of the barriers and facilitators for study participation and for compliance with oral health maintenance. The patients, in the control arm, presented their views regarding the acceptable length of waiting time for the intervention. Conclusion: The associations between periodontal and systemic health are increasingly recognized by the literature. Our study provided an insight into RA patients’ experiences and perceptions about oral health. It also highlighted some of the barriers and facilitators for participating in a periodontal interventional study for this group. We hope that our findings will support the design of larger interventional periodontal studies in patients with RA. The complex challenges faced by the burden of RA and the associated multimorbidities in this patient group might highlight opportunities to improve access to oral health services in this patient population. Knowledge Transfer Statement: This article provided insights into the experiences and perceptions of rheumatoid arthritis patients about their oral health to improve patient participation in a definitive clinical trial

A Digital Health Solution for Child Growth Monitoring at Home: Testing the Accuracy of a Novel “GrowthMonitor” Smartphone Application to Detect Abnormal Height and Body Mass Indices

Objective To develop and evaluate a smartphone application that accurately measures height and provides notifications when abnormalities are detected. Patients and Methods A total of 145 (75 boys) participants with a mean age ± SD of 8.7±4.5 years (range, 1.0-17.0 years), from the Children’s Hospital at Barts Health Trust, London, United Kingdom, were enrolled in the study. “GrowthMonitor” (UCL Creatives) iPhone application (GMA) measures height using augmented reality. Using population-based (UK-WHO) references, algorithms calculated height SD score (HSDS), distance from target height (THSDSDEV), and HSDS change over time (ΔHSDS). Pre-established thresholds discriminated normal/abnormal growth. The GMA and a stadiometer (Harpenden; gold standard) measured standing heights of children at routine clinic visits. A subset of parents used GMA to measure their child’s height at home. Outcome targets were 95% of GMA measurements within ±0.5 SDS of the stadiometer and the correct identification of abnormal HSDS, THSDSDEV, and ΔHSDS. Results Bland-Altman plots revealed no appreciable bias in differences between paired study team GMA and stadiometer height measurements, with a mean of the differences of 0.11 cm with 95% limits of agreement of −2.21 to 2.42 cm. There was no evidence of greater bias occurring for either shorter/younger children or taller/older children. The 2 methods of measurements were highly correlated (R=0.999). GrowthMonitor iPhone application measurements performed by parents in clinic and at home were slightly less accurate. The κ coefficient indicated reliable and consistent agreement of flag alerts for HSDS (κ=0.74) and THSDSDEV (κ=0.88) between 83 paired GMA and stadiometer measurements. GrowthMonitor iPhone application yielded a detection rate of 96% and 97% for HSDS-based and THSDSDEV-based red flags, respectively. Forty-two (18 boys) participants had GMA calculated ΔHSDS using an additional height measurement 6-16 months later, and no abnormal flag alerts were triggered for ΔHSDS values. Conclusion GrowthMonitor iPhone application provides the potential for parents/carers and health care professionals to capture serial height measurements at home and without specialized equipment. Reliable interpretation and flagging of abnormal measurements indicate the potential of this technology to transform childhood growth monitoring

Modelling autosomal dominant optic atrophy associated with OPA1 variants in iPSC-derived retinal ganglion cells

Autosomal dominant optic atrophy (DOA) is the most common inherited optic neuropathy, characterised by the preferential loss of retinal ganglion cells (RGCs), resulting in optic nerve degeneration and progressive bilateral central vision loss. Over 60% of genetically confirmed DOA patients carry variants in the nuclear OPA1 gene, which encodes for a ubiquitously expressed, mitochondrial GTPase protein. OPA1 has diverse functions within the mitochondrial network, facilitating inner membrane fusion and cristae modelling, regulating mitochondrial DNA maintenance and coordinating mitochondrial bioenergetics. There are currently no licensed disease-modifying therapies for DOA and the disease mechanisms driving RGC degeneration are poorly understood. Here, we describe the generation of isogenic, heterozygous OPA1 null iPSC (OPA1+/-) through CRISPR/Cas9 gene editing of a control cell line, in conjunction with the generation of DOA patient-derived iPSC carrying OPA1 variants, namely, the c.2708_2711delTTAG variant (DOA iPSC), and previously reported missense variant iPSC line (c.1334G>A, DOA+ iPSC) and CRISPR/Cas9 corrected controls. A two-dimensional (2D) differentiation protocol was used to study the effect of OPA1 variants on iPSC-RGC differentiation and mitochondrial function. OPA1+/-, DOA and DOA+ iPSC showed no differentiation deficit compared to control iPSC lines, exhibiting comparable expression of all relevant markers at each stage of differentiation. OPA1+/- and OPA1 variant iPSC-RGCs exhibited impaired mitochondrial homeostasis, with reduced bioenergetic output and compromised mitochondrial DNA maintenance. These data highlight mitochondrial deficits associated with OPA1 dysfunction in human iPSC-RGCs, and establish a platform to study disease mechanisms that contribute to RGC loss in DOA, as well as potential therapeutic interventions