Associations of central and peripheral blood pressure with cardiac structure and function in an adolescent birth cohort:the Avon Longitudinal Study of Parents and Children

LetterDiana L.S. Ferreira, Abigail Fraser, Laura D. Howe, Siana Jones, George Davey Smith, Debbie A. Lawlor, Robyn J. Tapp, Andy R. Ness, John E. Deanfield, Nish Chaturvedi, Alun D. Hughe

The Potential of N-Rich Plasma-Polymerized Ethylene (PPE:N) Films for Regulating the Phenotype of the Nucleus Pulposus

We recently developed a nitrogen-rich plasma-polymerized biomaterial, designated “PPE:N” (N-doped plasma-polymerized ethylene) that is capable of suppressing cellular hypertrophy while promoting type I collagen and aggrecan expression in mesenchymal stem cells from osteoarthritis patients. We then hypothesized that these surfaces would form an ideal substrate on which the nucleus pulposus (NP) phenotype would be maintained. Recent evidence using microarrays showed that in young rats, the relative mRNA levels of glypican-3 (GPC3) and pleiotrophin binding factor (PTN) were significantly higher in nucleus pulposus (NP) compared to annulus fibrosus (AF) and articular cartilage. Furthermore, vimentin (VIM) mRNA levels were higher in NP versus articular cartilage. In contrast, the levels of expression of cartilage oligomeric matrix protein (COMP) and matrix gla protein precursor (MGP) were lower in NP compared to articular cartilage. The objective of this study was to compare the expression profiles of these genes in NP cells from fetal bovine lumbar discs when cultured on either commercial polystyrene (PS) tissue culture dishes or on PPE:N with time. We found that the expression of these genes varies with the concentration of N ([N]). More specifically, the expression of several genes of NP was sensitive to [N], with a decrease of GPC3, VIM, PTN, and MGP in function of decreasing [N]. The expression of aggrecan, collagen type I, and collagen type II was also studied: no significant differences were observed in the cells on different surfaces with different culture time. The results support the concept that PPE:N may be a suitable scaffold for the culture of NP cells. Further studies are however necessary to better understand their effects on cellular phenotypes

Percutaneous revascularization for ischemic left ventricular dysfunction: Cost-effectiveness analysis of the REVIVED-BCIS2 trial

BACKGROUND: Percutaneous coronary intervention (PCI) is frequently undertaken in patients with ischemic left ventricular systolic dysfunction. The REVIVED (Revascularization for Ischemic Ventricular Dysfunction)-BCIS2 (British Cardiovascular Society-2) trial concluded that PCI did not reduce the incidence of all-cause death or heart failure hospitalization; however, patients assigned to PCI reported better initial health-related quality of life than those assigned to optimal medical therapy (OMT) alone. The aim of this study was to assess the cost-effectiveness of PCI+OMT compared with OMT alone. METHODS: REVIVED-BCIS2 was a prospective, multicenter UK trial, which randomized patients with severe ischemic left ventricular systolic dysfunction to either PCI+OMT or OMT alone. Health care resource use (including planned and unplanned revascularizations, medication, device implantation, and heart failure hospitalizations) and health outcomes data (EuroQol 5-dimension 5-level questionnaire) on each patient were collected at baseline and up to 8 years post-randomization. Resource use was costed using publicly available national unit costs. Within the trial, mean total costs and quality-adjusted life-years (QALYs) were estimated from the perspective of the UK health system. Cost-effectiveness was evaluated using estimated mean costs and QALYs in both groups. Regression analysis was used to adjust for clinically relevant predictors. RESULTS: Between 2013 and 2020, 700 patients were recruited (mean age: PCI+OMT=70 years, OMT=68 years; male (%): PCI+OMT=87, OMT=88); median follow-up was 3.4 years. Over all follow-ups, patients undergoing PCI yielded similar health benefits at higher costs compared with OMT alone (PCI+OMT: 4.14 QALYs, £22 352; OMT alone: 4.16 QALYs, £15 569; difference: −0.015, £6782). For both groups, most health resource consumption occurred in the first 2 years post-randomization. Probabilistic results showed that the probability of PCI being cost-effective was 0. CONCLUSIONS: A minimal difference in total QALYs was identified between arms, and PCI+OMT was not cost-effective compared with OMT, given its additional cost. A strategy of routine PCI to treat ischemic left ventricular systolic dysfunction does not seem to be a justifiable use of health care resources in the United Kingdom

Arrhythmia and death following percutaneous revascularization in ischemic left ventricular dysfunction: Prespecified analyses from the REVIVED-BCIS2 trial

BACKGROUND: Ventricular arrhythmia is an important cause of mortality in patients with ischemic left ventricular dysfunction. Revascularization with coronary artery bypass graft or percutaneous coronary intervention is often recommended for these patients before implantation of a cardiac defibrillator because it is assumed that this may reduce the incidence of fatal and potentially fatal ventricular arrhythmias, although this premise has not been evaluated in a randomized trial to date. METHODS: Patients with severe left ventricular dysfunction, extensive coronary disease, and viable myocardium were randomly assigned to receive either percutaneous coronary intervention (PCI) plus optimal medical and device therapy (OMT) or OMT alone. The composite primary outcome was all-cause death or aborted sudden death (defined as an appropriate implantable cardioverter defibrillator therapy or a resuscitated cardiac arrest) at a minimum of 24 months, analyzed as time to first event on an intention-to-treat basis. Secondary outcomes included cardiovascular death or aborted sudden death, appropriate implantable cardioverter defibrillator (ICD) therapy or sustained ventricular arrhythmia, and number of appropriate ICD therapies. RESULTS: Between August 28, 2013, and March 19, 2020, 700 patients were enrolled across 40 centers in the United Kingdom. A total of 347 patients were assigned to the PCI+OMT group and 353 to the OMT alone group. The mean age of participants was 69 years; 88% were male; 56% had hypertension; 41% had diabetes; and 53% had a clinical history of myocardial infarction. The median left ventricular ejection fraction was 28%; 53.1% had an implantable defibrillator inserted before randomization or during follow-up. All-cause death or aborted sudden death occurred in 144 patients (41.6%) in the PCI group and 142 patients (40.2%) in the OMT group (hazard ratio, 1.03 [95% CI, 0.82–1.30]; P =0.80). There was no between-group difference in the occurrence of any of the secondary outcomes. CONCLUSIONS: PCI was not associated with a reduction in all-cause mortality or aborted sudden death. In patients with ischemic cardiomyopathy, PCI is not beneficial solely for the purpose of reducing potentially fatal ventricular arrhythmias. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01920048

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

An Analysis of Undergraduate Elementary School Pre-Service Teachers\u27 Ability to Contextualize Fraction Expressions and Decontextualize Fraction Word Problems

The focus of this research was to expand on existing literature by providing information on elementary school pre-service teachers\u27 ability to contextualize fraction expressions and decontextualize fraction word problems. The elementary school pre-service teachers who participated in this study were enrolled in a mathematics for elementary school teachers content course in a college of education at a large university during the Spring 2016 semester. In this mixed-method study, the participants were given the Contextualization and Decontextualization of Fractions Instrument (CDFI) which assessed elementary school pre-service teachers\u27 ability to solve fraction word problems and identify decontextualized fraction word problems into expressions and contextualized fraction expressions into word problems. The elementary school pre-service teachers were given the CDFI before and after they completed a unit on fractions. Of the 52 participants who completed both the pre- and post- CDFI, 11 were selected to participant in think aloud interviews in which they decontextualized fraction expressions from word problems and solved and contextualized fraction word problems from expressions. Quantitative results showed an overall statistically significant difference in the elementary school pre-service teachers\u27 pre- and post- test scores. With the exception of two questions, all questions on the CDFI showed a statistically significant difference between the pre- and the post- test scores. No statistical significance was found in the responses to the question that required the elementary school pre-service teachers to identify the expression that matched the given fraction subtraction word problem. A large number of participants correctly identified the correct subtraction expression on the pre-test, and only slightly more of them were able to identify the correct subtraction expression on the post-test. No statistical significance was found in the responses to the question that required the elementary school pre-service teachers to explain their selection of a contextualized fraction multiplication expression. Though there was an increase in the elementary school pre-service teachers\u27 ability to explain their selection of the contextualized fraction multiplication expression, it was not statistically significant. The qualitative analysis of the think aloud interview data showed that some of the elementary school pre-service teachers struggled with contextualizing fraction expressions. Most of the elementary school pre-service teachers did not struggle with solving the fraction word problems, but did struggle with decontextualizing fraction multiplication word problems

A un lugar donde crezcan las flores. Prácticas artísticas en torno a la creación de universos ficcionales.

[ES] Este trabajo presenta diferentes propuestas multidisciplinares que surgen desde la introspección, la espontaneidad y la fabulación para crear universos ficcionales, relacionados con la esfera de la intimidad y las vivencias personales, e intentar abordar y canalizar inquietudes de carácter autobiográfico relacionadas con la infancia, la nostalgia, los paraísos perdidos y la necesidad del arte a nivel individual y colectivo. Su título, A un lugar donde crezcan las flores, hace referencia a un recorrido por nuestro proceso de exploración artística.[EN] This project presents different mulidisciplinar proposals that come from introspection, spontaneity and fabulation in order not only to create fictional universes related to intimacy and personal experiences, but also to try to address and direct ones worries, which have an autobiografic character related to love, childhood, nostalgia, lost paradises and the need of art individually and collectively. Its tittle To wards a place where flowers grow, refers to a journey through our process of artistic experimentation.Bono Tapp, L. (2021). A un lugar donde crezcan las flores. Prácticas artísticas en torno a la creación de universos ficcionales. Universitat Politècnica de València. http://hdl.handle.net/10251/170069TFG

Pre-Service Teachers’ Implementation of Physical and Virtual Manipulatives

With the accessibility of virtual manipulatives (apps and applets) in classrooms, it is necessary to reassess how these advancements may impact the learning process and research efforts. A possible approach is a framework that combines the well-known concrete (C), pictorial (P) and abstract (A) learning levels (CPA) with a proposed Virtual-level (V) (CPAV). The V-level includes digital and dynamic (non-static) components, which allows students’ virtual interaction with digital tools such as images, words, numbers and graphs. It also involves different sublevels: Virtual-Concrete, Virtual-Pictorial and Virtual Abstract. The framework will be discussed and demonstrated using easily available apps and applets (for example, NCTM Illuminations and National Library of Virtual Manipulatives). It is very important to understand what is involved in a virtual manipulative tool in order to provide for students’ learning needs. We will discuss mathematics pre-service teachers’ understanding and possible misconceptions of the framework while developing lesson plans and assessment activities. Several improvements are recommended in order to avoid participants’ misunderstandings. Most pre-service teachers demonstrated the ability to identify the levels involved in the instructional activities for the C, P and A levels in pre-, post and follow-up-tests, and lesson plans, but had a harder time with the V-sublevels. Participants are encouraged to bring their own iPads and computers

Physical and Virtual Manipulation Framework Conceptions of Undergraduate Pre-Service Teachers

The goal of this study is to analyze undergraduate elementary school pre-service teachers’ conceptions and misconceptions of physical and virtual manipulative materials using an interpretive framework. The framework involved the use of the Concrete, Pictorial and Abstract cognitive levels combined with the Virtual-level, or CPVA-framework. The CPVA instrument was used to answer two research questions related to participants’ understanding of CPVA-levels using the framework during a mathematics methods course. Pre-, post and follow-up test scores were analyzed. The participants demonstrated improvement from pre-test to post- and follow-up-tests. However, this improvement was limited by their understanding of the Virtual-level

Management of irritable bowel syndrome in primary care: the results of an exploratory randomised controlled trial of mebeverine, methylcellulose, placebo and a self-management website

Background: many patients with IBS suffer on-going symptoms. The evidence base is poor for IBS drugs but they are widely prescribed and advised in Guidelines. Cognitive Behavioural Therapy (CBT) can be helpful, but availability is poor in the NHS. We developed a web-based CBT self-management programme (Regul8) in partnership with patients and trialled it and common IBS medications in an exploratory factorial RCT to test trial procedures and provide information for a larger trial.Methods: patients, 16 to 60 years, with IBS symptoms fulfilling Rome III criteria were recruited via GP practices and randomised to over-encapsulated mebeverine, methylcellulose or placebo for 6 weeks and to 1 of 3 website conditions: Regul8 with a nurse telephone session and email support, Regul8 with minimal email support, or no website.Results: 135 patients recruited from 26 GP practices. Mean IBS SSS score 241.9 (sd 87.7), IBS-QOL 64 (sd 20) at baseline. 91% follow-up at 12 weeks. Mean IBS SSS decreased by 35 points from baseline to 12 weeks. There was no significant difference in IBS SSS or IBS-QOL score between medication or website groups at 12 weeks, or in medication groups at 6 weeks, or IBS-QOL in website groups at 6 weeks. However, IBS SSS at 6 weeks was lower in the No website group than the website groups (IBS SSS no website =162.8 (95% CI 137.4-188.3), website 197.0 (172.4 - 221.7), Website + telephone support 208.0 (183.1-233.0) p = 0.037). Enablement and Subjects Global Assessment of relief (SGA) were significantly improved in the Regul8 groups compared to the non-website group at 12 weeks (Enablement = 0 in 56.8% of No website group, 18.4% website, 10.5% Website + support, p = 0.001) (SGA; 32.4% responders in No website group, 45.7% website group, 63.2% website + support group, p = 0.035) Conclusions: This exploratory study demonstrates feasibility and high follow-up rates and provides information for a larger trial. Primary outcomes (IBS SS and IBS QOL) did not reach significance at 6 or 12 weeks, apart from IBS SSS being lower in the no-website group at 6 weeks - this disappeared by 12 weeks. Improved Enablement suggests patients with access to the Regul8 website felt better able to cope with their symptoms than the non-website group. Improved SGA score in the Regul8 groups may indicate some overall improvement not captured on other measures. Trial registration: ClinicalTrials.gov Identifier (NCT number): NCT00934973