Functionalized erythrocyte-derived optical nanoparticles to target ephrin-B2 ligands.

Over- or under-expression of erythropoietin-production human hepatocellular receptors (Eph) and their ligands are associated with various diseases. Therefore, these molecular biomarkers can potentially be used as binding targets for the delivery of therapeutic and/or imaging agents to cells characterized by such irregular expressions. We have engineered nanoparticles derived from erythrocytes and doped with the near-infrared (NIR) FDA-approved dye, indocyanine green. We refer to these nanoparticles as NIR erythrocyte-derived transducers (NETs). We functionalized the NETs with the ligand-binding domain of a particular Eph receptor, EphB1, to target the genetically modified human dermal microvascular endothelial cells (hDMVECs) with coexpression of EphB1 receptor and its ligand ephrin-B2. This cell model mimics the pathological phenotypes of lesional endothelial cells (ECs) in port wine stains (PWSs). Our quantitative fluorescence imaging results demonstrate that such functionalized NETs bind to the ephrin-B2 ligands on these hDMVECs in a dose-dependent manner that varies sigmoidally with the number density of the particles. These nanoparticles may potentially serve as agents to target PWS lesional ECs and other diseases characterized with over-expression of Eph receptors or their associated ligands to mediate phototherapy

The effect of a rapid heating rate, mechanical vibration and surfactant chemistry on the structure-property relationships of epoxy/clay nanocomposites

The role of processing conditions and intercalant chemistry in montmorillonite clays on the dispersion, morphology and mechanical properties of two epoxy/clay nanocomposite systems was investigated in this paper. This work highlights the importance of employing complementary techniques (X-ray diffraction, small angle X-ray scattering, optical microscopy and transmission electron microscopy) to correlate nanomorphology to macroscale properties. Materials were prepared using an out of autoclave manufacturing process equipped to generate rapid heating rates and mechanical vibration. The results suggested that the quaternary ammonium surfactant on C30B clay reacted with the epoxy during cure, while the primary ammonium surfactant (I.30E) catalysed the polymerisation reaction. These effects led to important differences in nanocomposite clay morphologies. The use of mechanical vibration at 4 Hz prior to matrix gelation was found to facilitate clay dispersion and to reduce the area fraction of I.30E clay agglomerates in addition to increasing flexural strength by over 40%

Experiences of patients and professionals participating in the HITS home blood pressure telemonitoring trial: a qualitative study: Table 1

Objectives To explore the experiences of patients and professionals taking part in a randomised controlled trial (RCT) of remote blood pressure (BP) telemonitoring supported by primary care. To identify factors facilitating or hindering the effectiveness of the intervention and those likely to influence its potential translation to routine practice. Design Qualitative study adopting a qualitative descriptive approach. Participants 25 patients, 11 nurses and 9 doctors who were participating in an RCT of BP telemonitoring. A maximum variation sample of patients from within the trial based on age, sex and deprivation status of the practice was sought. Setting 6 primary care practices in Scotland. Method Data were collected via taped semistructured interviews. Initial thematic analysis was inductive. Multiple strategies were employed to ensure that the analysis was credible and trustworthy. Results Prior to the trial, both patients and professionals were reluctant to increase the medication based on single BP measurements taken in the surgery. BP measurements based on multiple electronic readings were perceived as more accurate as a basis for action. Patients using telemonitoring became more engaged in the clinical management of their condition. Professionals reported that telemonitoring challenged existing roles and work practices and increased workload. Lack of integration of telemonitoring data with the electronic health record was perceived as a drawback. Conclusions BP telemonitoring in a usual care setting can provide a trusted basis for medication management and improved BP control. It increases patients’ engagement in the management of their condition, but supporting telemetry and greater patient engagement can increase professional workloads and demand changes in service organisation. Successful service design in practice would have to take account of how additional roles and responsibilities could be realigned with existing work and data management practices. The embedded qualitative study was included in the protocol for the HITS trial registered with ISRCTN no. 7261427

Improving recruitment to clinical trials with a register of a million patients who agree to the use of their clinical records for research in the Scottish Health Research Register (SHARE)

The UK's technical ability to identify people eligible for medical research is not yet matched by a practical capability to approach them directly to ask them to consider participation in those studies. The consequence is that recruitment to research is more difficult than necessary and some projects fail. This makes Britain a less attractive location to undertake clinical research than it should be. In order to overcome this increasingly important obstacle, we wanted to develop a register of Scottish residents who wish to be considered for participation in a range of studies. This was an oral presentation given at the Clinical Trials Methodology conference 2011, 4-5 October 2011, Bristol, UK

Curating Complex, Dynamic and Distributed Data: Telehealth as a Laboratory for Strategy

Telehealth monitoring data is now being collected across large populations of patients with chronic diseases such as stroke, hypertension, COPD and dementia. These large, complex and heterogeneous datasets, including distributed sensor and mobile datasets, present real opportunities for knowledge discovery and re-use, however they also generate new challenges for curation. This paper uses qualitative research with stakeholders in two nationally-funded telehealth projects to outline the perceptions, practices and preferences of different stakeholders with regard to data curation. Telehealth provides a living laboratory for the very different challenges implicit in designing and managing data infrastructure for embedded and ubiquitous computing. Here, technical and human agents are distributed, and interaction and state change is a central component of design, rather than an inconvenient challenge to it. The authors argue that there are lessons to be learned from other domains where data infrastructure has been radically rethought to address these challenge

Acceptability and perceived barriers and facilitators to creating a national research register to enable ’direct to patient’ enrolment into research: the Scottish Health Research Register (SHARE)

BackgroundDifficulties with recruitment pose a major, increasingly recognised challenge to the viability of research. We sought to explore whether a register of volunteers interested in research participation, with data linkage to electronic health records to identify suitable research participants, would prove acceptable to healthcare staff, patients and researchers.MethodsWe undertook a qualitative study in which a maximum variation sampling approach was adopted. Focus groups and interviews were conducted with patients, general practitioners (GP), practice managers and health service researchers in two Scottish health boards. Analysis was primarily thematic to identify a range of issues and concerns for all stakeholder groups.ResultsThe concept of a national research register was, in general, acceptable to all stakeholder groups and was widely regarded as beneficial for research and for society. Patients, however, highlighted a number of conditions which should be met in the design of a register to expedite confidence and facilitate recruitment. They also gave their perceptions on how a register should operate and be promoted, favouring a range of media. GPs and practice managers were primarily concerned with the security and confidentiality of patient data and the impact a register may have on their workload. Researchers were supportive of the initiative seeing advantages in more rapid access to a wider pool of patients. They did raise concerns that GPs may be able to block access to personal patient data held in general practice clinical systems and that the register may not be representative of the whole population.ConclusionsThis work suggests that patients, healthcare staff and researchers have a favourable view of the potential benefits of a national register to identify people who are potentially eligible and willing to participate in health related research. It has highlighted a number of issues for the developers to incorporate in the design of research registers

A manually annotated Actinidia chinensis var. chinensis (kiwifruit) genome highlights the challenges associated with draft genomes and gene prediction in plants

Most published genome sequences are drafts, and most are dominated by computational gene prediction. Draft genomes typically incorporate considerable sequence data that are not assigned to chromosomes, and predicted genes without quality confidence measures. The current Actinidia chinensis (kiwifruit) 'Hongyang' draft genome has 164\ua0Mb of sequences unassigned to pseudo-chromosomes, and omissions have been identified in the gene models

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Children’s anthropomorphic and anthropocentric ideas about micro-organisms

Different views exist about whether anthropomorphic ideas assist or hinder learning in biology. This paper discussesthe anthropomorphic and anthropocentric ideas children have about micro-organisms, and whether they affecttheir understanding. The research was carried out in primary and secondary schools in the South of England andinvolved 414 children aged 7, 11 and 14 years. Three different research techniques were used to elicit their ideas.Anthropomorphic and anthropocentric ideas about micro-organisms are apparent in responses from all age groups.Anthropomorphic ideas seem to help children to explain their understanding of some aspects of micro-organismsbut the imbalance in children’s anthropocentric views of micro-organisms appears to prohibit them consideringother aspects of micro-organisms; for example, the importance of their role in decomposition and cycling of matter,or their beneficial technological applications. The focus on the danger micro-organisms are thought to pose tohuman health creates a hostile view of micro-organisms and this may inhibit future learning