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During a project investigating pea viruses in the United Kingdom (UK) and developing a workflow for high throughput sequencing (HTS) in crop surveillance, pea necrotic yellow dwarf virus (PNYDV) was identified at one site, along with pea enation mosaic virus-1, pea enation mosaic virus-2, pea enation mosaic virus satellite RNA, pea seed-borne mosaic virus and turnip yellows virus. Following an initial finding of small PNYDV contigs by RNA sequencing protocol on a MiSeq (Illumina), confirmation and prevalence testing by PCR and Sanger sequencing determined the average PNYDV prevalence to be 3%. This is the first report of PNYDV, and a nanovirus, in the UK. Initial characterisation of the octopartite genome by PCR revealed that component DNA N had a truncated sequence that differed from those previously reported. This led to confirmation testing using rolling circle amplification (RCA) into the MiSeq and then MinION (Oxford Nanopore). Sequence was obtained by both RCA-MiSeq and RCA-MinION, with the MinION producing more complete genomes than RCA-MiSeq. Data obtained from sequencing was used to provide an initial estimation of the genomic formula of PNYDV. Previous work has looked into the comparing each method, however within this study it is shown how these methods can be used together. The truncated sequence for DNA N was also found by RCA-MiSeq, RCA-MinION and confirmed by specific primers, but further work is required to understand the impact of this truncation.

International audience; Accumulation of excess iron in the body, or systemic iron overload, results from a variety of causes. The concentration of iron in the liver is linearly related to the total body iron stores and, for this reason, quantification of liver iron concentration (LIC) is widely regarded as the best surrogate to assess total body iron. Historically assessed using biopsy, there is a clear need for noninvasive quantitative imaging biomarkers of LIC. MRI is highly sensitive to the presence of tissue iron and has been increasingly adopted as a noninvasive alternative to biopsy for detection, severity grading, and treatment monitoring in patients with known or suspected iron overload. Multiple MRI strategies have been developed in the past 2 decades, based on both gradient-echo and spin-echo imaging, including signal intensity ratio and relaxometry strategies. However, there is a general lack of consensus regarding the appropriate use of these methods. The overall goal of this article is to summarize the current state of the art in the clinical use of MRI to quantify liver iron content and to assess the overall level of evidence of these various methods. Based on this summary, expert consensus panel recommendations on best practices for MRI-based quantification of liver iron are provided.

Dementia is a global health challenge and currently the focus of a coordinated international response articulated through the notion of dementia-friendly communities and initiatives (DFCIs). Yet, while increasing research attention has been paid to the social and spatial dimensions to life with dementia in a neighbourhood setting, the temporalities of dementia have been largely overlooked. This article sets out different aspects of the lived experience of time for people with dementia and unpaid carers, before exploring the temporal politics of formal dementia care and support. The authors show that time is a site for material struggle and a marker of unequal relations of power. People with dementia and unpaid carers are disempowered through access to formal care, and this is illustrated in their loss of (temporal) autonomy and limited options for changing the conditions of the care received. The authors advocate for a time-space configured understanding of the relationship with neighbourhood and foreground a tempo-material understanding of dementia. Set against the backdrop of austerity policy in the UK, the findings reveal that ongoing budgetary restrictions have diminished the capacity for social care to mediate in questions of social justice and inequality, at times even compounding inequity. Funding Agencies|Economic and Social Research Council [ES/L001772/1]; National Institute for Health Research

Summary We aimed to identify risk factors for adverse outcomes in pregnancies of women with sickle cell disease (SCD) and develop risk prediction models. Models were derived from a retrospective cohort of pregnant women with SCD and constructed using generalised estimating equation logistic regression, with clustering by woman. Maternal event(s) consisted of acute anaemia; cardiac, pulmonary, hepatobiliary, musculoskeletal, skin, splenic, neurological or renal complications, multi‐organ failure, venous thromboembolism, admission‐requiring vaso‐occlusive events (VOE), red cell transfusion, mortality or hypertensive disorder of pregnancy. Fetal events included preterm birth, small‐for‐gestational‐age or perinatal mortality. Of 199 pregnancies, 71% and 45% resulted in adverse maternal and fetal outcomes respectively. Low first‐trimester haemoglobin, admission‐requiring VOE in the year before pregnancy, multiple transfusions before pregnancy, SCD genotype and previous cardiac complications predicted maternal risk. Younger age and SCD genotype allowed early prediction of fetal risk (model‐F1). Adding maternal event(s) and high lactate dehydrogenase enabled re‐assessment of fetal risk with advancing gestation (model‐F2). Models were well calibrated and moderately discriminative for maternal outcome (c‐statistic 0·81, cross‐validated value 0·79) and fetal outcome (model‐F1 c‐statistic 0·68, cross‐validated value 0·65; model‐F2 c‐statistic 0·72, cross‐validated value 0·68). The models will allow early identification of women with SCD at high risk of adverse events, permitting early targeted interventions and ongoing fetal risk re‐assessment enabling intensification of surveillance and optimisation of delivery timing.

MRI quantification of liver iron concentration (LIC) using R2 or R2* relaxometry requires offline post-processing causing reporting delays, administrative overhead, and added costs. A prototype 3D multi-gradient-echo pulse sequence, with inline post-processing, allows immediate calculation of LIC from an R2* map (inline R2*-LIC) without offline processing. We compared inline R2*-LIC to FerriScan and offline R2* calibration methods. Forty patients (25 women, 15 men; age 18–82 years), prospectively underwent FerriScan and the prototype sequence, which produces two R2* maps, with and without fat modeling, as well as an inline R2*-LIC map derived from the R2* map with fat modeling, with informed consent. For each map, the following contours were drawn: ROIs, whole-axial-liver contour, and an exact copy of contour utilized by FerriScan. LIC values from the FerriScan report and those calculated using an alternative R2 calibration were the reference standards. Results were compared using Pearson and interclass correlation coefficients (PCC, ICC), linear regression, Bland-Altman analysis, and estimation of area under the receiver operator curve (ROC-AUC). Inline R2*-LIC demonstrated good agreement with the reference standards. Compared to FerriScan, inline R2*-LIC with whole-axial-liver contour, ROIs, and FerriScan contour demonstrated PCC of 94.8%, 94.8%, and 92%; ICC 93%, 92.7%, and 90.2%; regression slopes 1.004, 0.974, and 1.031; mean bias 5.54%, 10.91%, and 0.36%; and ROC-AUC estimates 0.903, 0.906, and 0.890 respectively. Agreement was maintained when adjusted for sex, age, diagnosis, liver fat content, and fat-water swap. Inline R2*-LIC provides robust and comparable quantification of LIC compared to FerriScan, without the need for offline post-processing. • In patients being treated for iron overload with chelation therapy, liver iron concentration (LIC) is regularly assessed in order to monitor and adjust therapy. • Magnetic resonance imaging (MRI) is commonly used to quantify LIC. Several R 2 and R 2 * methods are available, all of which require offline post-processing. • A novel R 2 * MRI method allows for immediate calculation of LIC and provides comparable quantification of LIC to the FerriScan and recently published alternative R 2 * methods.

Sickle cell disease patients commonly present to an emergency department (ED) due to acute vaso-occlusive pain episodes (VOEs), also known as vaso-occlusive crises (VOCs). Unsatisfactory patient care leads to preventable morbidity, mortality, and substantial financial costs. This study investigated the current use of sickle cell disease patient-directed physician education (PDPE) in the clinical setting and also explored opportunities for improvement. A qualitative phenomenologic design was used with semi-structured in-depth interviews. Open-ended questions were used to probe participant's experiences with EDs, the feasibility of a PDPE program as well as barriers and facilitators to PDPE. A total of nine patients and eight physicians participated in the study. Three major themes were identified: divergent challenges to patient recommendations, new targets for sickle cell disease education and triage process: not heard and not seen. Numerous challenges exist to the implementation and optimization of PDPE with sickle cell disease triage processes and nursing support identified as influential factors. Paramount to the process of improving PDPE is physicians perceiving patients as credible sources of information, especially as it relates to generalized concerns of opioid dosing. A patient provided written or digital education tool can be considered to facilitate PDPE to ease communication strain on patients while increasing communication efficiency.

Background: In the UK, around 500–600 people a year sustain traumatic injuries to the spinal cord, half of which involve the cervical spine. UK ambulance guidelines stipulate that if immobilisation is indicated, the entire spine should be immobilised using an orthopaedic scoop stretcher, head restraints and a rigid cervical collar. However, the use of cervical collars is being debated in the paramedic profession. Although they were originally considered harmless and used as a precautionary measure, an increasing amount of evidence suggests otherwise and it is argued that they can do more harm than good. Therefore, it is debatable whether using them is consistent with the principles of patient safety and evidence-based practice. Aim: A literature review was carried out to comprehensively examine research surrounding the adverse effects of cervical collars and the range of movement they allow to gain a comprehensive understanding of their efficacy. Methods: The EBSCOhost Health Science Research database was searched. Seven articles were found and chosen for inclusion in the literature review. Results: Two themes were identified regarding cervical collars: adverse effects and range of movement. Conclusion: Evidence suggests that cervical collars can cause more harm than good, and UK ambulance guidelines for spinal immobilisation should be reconsidered.

The purpose of this study was to compare clinical decision-making in iron overload patients using FerriScan and an R2*-based approach. One-hundred and six patients were imaged at two consecutive timepoints (454 ± 158 days) on a 1.5-T Siemens MAGNETOM Avanto Fit scanner. For both timepoints, patients underwent the standard FerriScan MRI protocol. During the second exam, each patient additionally underwent R2*-MRI mapping. For each patient, a retrospective (simulated) decision was made to increase, decrease, or maintain chelator levels. Two different decision models were considered: The fixed threshold model assumed that chelator adjustments are based strictly on fixed liver iron concentration (LIC) thresholds. Decisions made with this model depend only on the most recent LIC value and do not require any clinician input. The second model utilized decisions made by two hematologists retrospectively based on trends between two consecutive LIC values. Agreement (κA) between hematologists (i.e., interobserver variability) was compared with the agreement (κB) between a single hematologist using the two different LIC techniques. Good agreement between R2*- and FerriScan-derived decisions was achieved for the fixed threshold model. True positive/negative rates were greater than 80%, and false positive/negative rates were less than 10%. ROC analysis yielded areas under the curve greater than 0.95. In the second model, the agreement in clinical decision-making for the two scenarios (κA vs. κB) was equal at the 95% confidence level. Switching to R2*-based LIC estimation from FerriScan has the same level of agreement in patient management decisions as does switching from one hematologist to another. • Good agreement between R2*- and FerriScan-derived decisions in liver iron overload patient management • Switching to R2*-based LIC estimation from FerriScan has the same level of agreement in patient management decisions as does switching from one hematologist to another.

Friction drilling is a non-conventional hole-making process suitable for thin-section, ductile metals. During friction drilling, heat is generated due to tool rotation and the resulting flow of metal creates a bushing on the exit side of the hole. The bushing offers a longer engagement length for any subsequent thread making process. The threaded holes in this study were created by friction drilling and thread forming in 6082-T6 aluminium alloy. Four scenarios of the threaded holes were created with four levels of rotation rates of friction drilling processes (2000 rpm to 4000 rpm) and the mechanical properties of the threaded holes were compared. It was shown that 3000–3500 rpm is the optimum range of the rotation rate that achieved the higher load-bearing capacities (i.e., resistance to thread stripping) of 5.0–5.5 kN. In addition, the regions close to the thread surfaces in all scenarios were found to have experienced localised hardening to a hardness from 113 HV to around 125 HV.

This realist review of the literature provided a contemporary understanding of neighbourhoods and dementia and described how people living with dementia and their neighbourhood interacted via ongoing place-making and remaking processes. Drawing on 44 articles, neighbourhoods were revealed to have fluid and dynamic qualities where people with dementia used their strength and resources to connect to significant people and places. The review also indicated that the person with dementia–neighbourhood relationship was underpinned by four themes: ‘home’, ‘social interactions’, ‘activities’ and ‘transportation’. Further research is encouraged to use innovative, participatory methods to explore the neighbourhood–dementia nexus in depth whilst paying close attention to social inclusion and diversity.

This chapter explores the understanding behind the emerging dementia-friendly communities (DFC) agenda. A five-year international qualitative study investigated the experience of the neighbourhood for people living with dementia and their care partners. Despite efforts to place people with dementia at the heart of the DFC movement, limited attention has been given to their actions and agency in a neighbourhood context. Spatial and affective practices of people living with dementia highlight the idea of ‘enabling neighbourhoods’. The chapter also notes the importance of engagement with diverse places and social opportunities in the neighbourhood to managing life with dementia alongside keeping up with wellbeing and social health. Ultimately, research shows the value of attending to the ‘doing’ of the neighbourhood, the transformative impact it can have on social relations over time, and the influence of people with dementia as agents of change.

This chapter tackles the report findings of Neighbourhoods: Our People, Our Places (N: OPOP) based on the experiences of people living alone with dementia from Greater Manchester, Scotland and Sweden. It also examines a subset of data from the N: OPOP project of people living alone with dementia establishing social networks and relationships in a neighbourhood context. Multiple data-collection methods were used such as semi-structured interviews, walking interviews, guided home tours and social network mapping, which were conducted with fourteen community-dwelling people living alone with dementia situated across the three international study sites. Thematic analysis revealed four main themes: making the effort to stay connected, befriending by organisations and facilitated friendships, the quiet neighbourhood atmosphere, and changing social connections. Moreover, the analysis suggests that people living alone with dementia were active agents that took control of finding and maintaining relationships and social networks in a lived neighbourhood. The findings indicate the need to raise awareness on policy, practice and creative ways to connect.

This chapter highlights the importance of situations and conditions wherein people live with dementia beyond care settings. Most research on dementia primarily focuses on disorientation in time and space. In line with the pathologising perspective of dementia in police reports or newpaper articles, outdoor spaces and mobility for affected individuals were often problematised. According to research, neighbourhoods are multi-dimensional in terms of being amalgamations of social, physical, real, and imagined spaces that hold varying importance in each person. Thus, therapeutic design in dementia studies focuses to mitigate risk and threat in environments by tackling supportive properties and features for people with dementia. The chapter also explains how the book contributes to the emerging capacity-oriented approach to dementia.

This chapter explains how the book has demonstrated the diversity of theoretical and conceptual approaches to people living with dementia. The idea of a neighbourhood implies an urban bias that holds particular meaning within Global North nations, which also largely undermines the rural experience of living with dementia. Neighbourhood, then, becomes a slippery concept that simultaneously covers perspectives and lived phenomena. The chapter acknowledges how the neighbourhood perspective has limitations to the emplaced lives of people with dementia. Additionally, intersectional understanding helped spark recognition of the significance of diversity of people with dementia. However, silence remains the lived experience of most people living with dementia. The chapter also includes possible improvements to policies, research, and practices addressing dementia.

This chapter looks into the significance of neighbourhoods for people living with dementia in line with social connection, engagement, and interaction. It also includes the nature of associations people have in the immediate locale in relation to geographic proximity. In literature, outdoor spaces, built environments, and everyday technologies are identified as the three domains of activity for neighbourhoods. According to the ESRC/NIHR-funded Neighbourhoods: Our People, Our Places research, relationships are constituted through a relationship sense of place that can facilitate belonging and inclusion. Moreover, local social connections act as channels for information, interaction, support, and metaphorical safety nets in exceptional circumstances. However, local connections for people with dementia could extend beyond the conventional neighbourhoods. Viewing neighbourhoods as relational phenomena gives the perspective of understanding the overlooked geographies of everyday life with dementia.

While doses of deferiprone up to 75 mg/kg/d have been demonstrated to be effective in cardiac iron removal, their efficacy in the reduction of liver iron has been equivocal. The aim of this study was to evaluate the effect of deferiprone dose on liver iron concentrations in adult iron overload patients.A single-centered, retrospective, cohort observational study was conducted involving 71 patients exposed to deferiprone doses up to 113 mg/kg/d between January 2009 and June 2015 for a median of 33 months.At the end of the study period, liver iron measured by R2 MRI was reduced by a mean 1.7 mg/g dw. A dose effect was observed, with incremental reductions of 2.8 mg/g dw in end of study LIC for every 10 mg/kg/d higher dose of deferiprone (P 0.001). A dose effect was also observed in end of study ferritin and cardiac iron concentration measured by T2* MRI (P 0.0001 and P = 0.048, respectively). No associations between adverse effects and deferiprone dose were observed, but there was a trend toward higher rates of agranulocytosis at higher doses and two of three hereditary hemochromatosis patients developed this complication.The present study failed to demonstrate that the use of deferiprone at90 mg/kg/d was associated with increased risk of agranulocytosis or neutropenia, but did demonstrate more effective liver iron control in iron overload patients.

Rose cryptic virus-1 (RoCV1) also known as Rosa multiflora cryptic virus is a partitivirus affecting roses, one of the most important ornamental crops worldwide. RoCV1 has previously been reported in the US, Canada and New Zealand, and has now been identified in the United Kingdom for the first time. Using High Throughput Sequencing (HTS) RoCV1 sequences were found in two samples collected in 2007 and 2012. This discovery led to the development of a RT-qPCR (TaqMan) assay for the detection of this virus. As part of a rose virus survey in the UK, 251 samples were analysed using the newly developed RoCV1 RT-qPCR test, following ELISA analysis for other common rose viruses. The results of the RT-qPCR test were confirmed using published conventional PCR primers and Sanger sequencing of amplified products. Results suggest that RoCV1 could have been infecting roses in the UK since at least 2007, with a large number of recently collected samples (43%) found to be infected. Cryptoviruses are not thought to cause direct economic losses in their plant host, although it is not clear what impact they might have in mixed infections.

Blood circulation is the main distribution route for systemic delivery and the possibility to manipulate red blood cells (RBCs) by attaching nanoparticles to their surface provides a great opportunity for cargo delivery into tissues. Nanocarriers attached to RBCs can be delivered to specific organs orders of magnitude faster than if injected directly into the bloodstream. Another advantage is a shielding from recognition by the immune system, thereby increasing the efficiency of delivery. We present a high-throughput microfluidic method that can monitor the shape of drifting cells due to interactions with nanoparticles and characterize the 3D dispersion of fluorescent silica nanoparticles at the surface of RBCs. The combination of fluorescence microscopy with image analysis demonstrates that the adsorption of silica nanoparticles onto the surface of RBCs is strongly influenced by electrostatic interactions. A reduced number of intact RBCs with increasing nanoparticle concentration beyond a certain threshold points to a toxicity mechanism associated with the nanoparticle adsorption at the surface of RBCs.

The extent of social isolation experienced by people living with dementia who reside in the community has been well acknowledged, yet little is known about how people living alone with dementia maintain neighbourhood-based connections. The purpose of this study is to examine the experiences of people with dementia who live alone, focusing upon how they establish social networks and relationships in a neighbourhood context, and how they are supported to maintain this social context within everyday life. Multiple data collection methods were used including, semi-structured interviews, walking interviews, guided home tours and social network mapping, which were conducted with 14 community-dwelling people living alone with dementia (11 women and three men) situated across the three international study sites in England, Scotland and Sweden. Data were analysed using thematic analysis. The analysis revealed four main themes: (a) making the effort to stay connected; (b) befriending by organisations and facilitated friendships; (c) the quiet neighbourhood atmosphere; and (d) changing social connections. The analysis suggests that people with dementia who live alone were active agents who took control to find and maintain relationships and social networks in the neighbourhood. Our findings indicate the need to raise awareness about this specific group in both policy and practice, and to find creative ways to help people connect through everyday activities and by spontaneous encounters in the neighbourhood. Funding: Swedish Riksbankens Jubileumsfond [M10-0187:1]; Economic and Social Research Council (ESRC)UK Research & Innovation (UKRI)Economic & Social Research Council (ESRC); National Institute for Health Research (NIHR)National Institute for Health Research (NIHR)

Dementia-friendly communities herald a shift toward the neighbourhood as a locus for the care and support of people with dementia, sparking growing interest in the geographies of dementia care and raising questions over the shifting spatial and social experience of the condition. Existing research claims that many people with dementia experience a shrinking world whereby the boundaries to their social and physical worlds gradually constrict over time, leading to a loss of control and independence. This paper reports a five-year, international study that investigated the neighbourhood experience of people with dementia and those who care for and support them. We interrogate the notion of a shrinking world and in so doing highlight an absence of attention paid to the agency and actions of people with dementia themselves. The paper draws together a socio-relational and embodied-material approach to question the adequacy of the shrinking world concept as an explanatory framework and to challenge reliance within policy and practice upon notions of place as fixed or stable. We argue instead for the importance of foregrounding lived place and attending to social practices and the networks in which such practices evolve. Our findings have implications for policy and practice, emphasising the need to bolster the agency of people living with dementia as a route to fostering accessible and inclusive neighbourhoods. Funding agencies: Economic and Social Research Council (ESRC; part of UK Research and Innovation); National Institute for Health Research (NIHR).