Summary Background Cardiosphere-derived cells (CDCs) reduce scarring after myocardial infarction, increase viable myocardium, and boost cardiac function in preclinical models. We aimed to assess ...safety of such an approach in patients with left ventricular dysfunction after myocardial infarction. Methods In the prospective, randomised CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction (CADUCEUS) trial, we enrolled patients 2–4 weeks after myocardial infarction (with left ventricular ejection fraction of 25–45%) at two medical centres in the USA. An independent data coordinating centre randomly allocated patients in a 2:1 ratio to receive CDCs or standard care. For patients assigned to receive CDCs, autologous cells grown from endomyocardial biopsy specimens were infused into the infarct-related artery 1·5–3 months after myocardial infarction. The primary endpoint was proportion of patients at 6 months who died due to ventricular tachycardia, ventricular fibrillation, or sudden unexpected death, or had myocardial infarction after cell infusion, new cardiac tumour formation on MRI, or a major adverse cardiac event (MACE; composite of death and hospital admission for heart failure or non-fatal recurrent myocardial infarction). We also assessed preliminary efficacy endpoints on MRI by 6 months. Data analysers were masked to group assignment. This study is registered with ClinicalTrials.gov , NCT00893360. Findings Between May 5, 2009, and Dec 16, 2010, we randomly allocated 31 eligible participants of whom 25 were included in a per-protocol analysis (17 to CDC group and eight to standard of care). Mean baseline left ventricular ejection fraction (LVEF) was 39% (SD 12) and scar occupied 24% (10) of left ventricular mass. Biopsy samples yielded prescribed cell doses within 36 days (SD 6). No complications were reported within 24 h of CDC infusion. By 6 months, no patients had died, developed cardiac tumours, or MACE in either group. Four patients (24%) in the CDC group had serious adverse events compared with one control (13%; p=1·00). Compared with controls at 6 months, MRI analysis of patients treated with CDCs showed reductions in scar mass (p=0·001), increases in viable heart mass (p=0·01) and regional contractility (p=0·02), and regional systolic wall thickening (p=0·015). However, changes in end-diastolic volume, end-systolic volume, and LVEF did not differ between groups by 6 months. Interpretation We show intracoronary infusion of autologous CDCs after myocardial infarction is safe, warranting the expansion of such therapy to phase 2 study. The unprecedented increases we noted in viable myocardium, which are consistent with therapeutic regeneration, merit further assessment of clinical outcomes. Funding US National Heart, Lung and Blood Institute and Cedars-Sinai Board of Governors Heart Stem Cell Center.
Objectives This study sought to report full 1-year results, detailed magnetic resonance imaging analysis, and determinants of efficacy in the prospective, randomized, controlled CADUCEUS ...(CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction) trial. Background Cardiosphere-derived cells (CDCs) exerted regenerative effects at 6 months in the CADUCEUS trial. Complete results at the final 1-year endpoint are unknown. Methods Autologous CDCs (12.5 to 25 × 106 ) grown from endomyocardial biopsy specimens were infused via the intracoronary route in 17 patients with left ventricular dysfunction 1.5 to 3 months after myocardial infarction (MI) (plus 1 infused off-protocol 14 months post-MI). Eight patients were followed as routine-care control patients. Results In 13.4 months of follow-up, safety endpoints were equivalent between groups. At 1 year, magnetic resonance imaging revealed that CDC-treated patients had smaller scar size compared with control patients. Scar mass decreased and viable mass increased in CDC-treated patients but not in control patients. The single patient infused 14 months post-MI responded similarly. CDC therapy led to improved regional function of infarcted segments compared with control patients. Scar shrinkage correlated with an increase in viability and with improvement in regional function. Scar reduction correlated with baseline scar size but not with a history of temporally remote MI or time from MI to infusion. The changes in left ventricular ejection fraction in CDC-treated subjects were consistent with the natural relationship between scar size and ejection fraction post-MI. Conclusions Intracoronary administration of autologous CDCs did not raise significant safety concerns. Preliminary indications of bioactivity include decreased scar size, increased viable myocardium, and improved regional function of infarcted myocardium at 1 year post-treatment. These results, which are consistent with therapeutic regeneration, merit further investigation in future trials. (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction CADUCEUS; NCT00893360 )
Global trade and the movement of people accelerate biological invasions by spreading species worldwide. Biosecurity measures seek to allow trade and passenger movements while preventing incursions ...that could lead to the establishment of unwanted pests, pathogens, and weeds. However, few data exist to evaluate whether changes in trade volumes, passenger arrivals, and biosecurity measures have altered rates of establishment of nonnative species over time. This is particularly true for pathogens, which pose significant risks to animal and plant health and are consequently a major focus of biosecurity efforts but are difficult to detect. Here, we use a database of all known plant pathogen associations recorded in New Zealand to estimate the rate at which new fungal pathogens arrived and established on 131 economically important plant species over the last 133 years. We show that the annual arrival rate of new fungal pathogens increased from 1880 to about 1980 in parallel with increasing import trade volume but subsequently stabilised despite continued rapid growth in import trade and recent rapid increases in international passenger arrivals. Nevertheless, while pathogen arrival rates for crop and pasture species have declined in recent decades, arrival rates have increased for forestry and fruit tree species. These contrasting trends between production sectors reflect differences in biosecurity effort and suggest that targeted biosecurity can slow pathogen arrival and establishment despite increasing trade and international movement of people.
This study examines students' perceptions of the outcomes and processes of engaged reading in classrooms prioritizing engagement through self-selected, self-paced reading of compelling young adult ...literature. The primary data were 71 end-of-year student interviews, supported by end-of-year teacher interviews, biweekly observational data, on-the-fly conversations with students, and video/audio records of student-initiated book discussions. An inductive analysis yielded 15 main categories of outcomes, including changes in students' identities, in their sense of agency, and in their relational, moral, and intellectual lives. The web of relationships among the processes and outcomes is examined through 317 causal statements made by students in interviews. Finally, a case study illustrates the cascading and reciprocal effects of engaged reading on one student's development. These adolescents showed, to varying degrees, an awareness of these processes and self-transformations, and thus a sense of agency with respect to their own development-their personhood and future narratives. This study raises questions about the adequacy of existing models of engagement for explaining students' engaged reading experiences and about currently advocated approaches to teaching English language arts that (a) minimize the roles of engagement and fiction, (b) require students to read the same text, (c) focus on engaged reading as an individual cognitive act without regard for the social nature of literate and human development, and (d) expect uniform outcomes across students.
People living with HIV (PLH) suffer disproportionately from the chronic diseases exacerbated by smoking tobacco. We performed a systematic review and meta-analysis to establish the relative ...prevalence of smoking among PLH.
We included observational studies reporting current smoking rates among PLH and comparators without HIV. We searched Medline, EMBASE, LILACS and SciELO from inception to 31 August 2019. We excluded studies that recruited participants with smoking related illness. We used a random effects model to estimate the odds ratio for current smoking in PLH and people without HIV. We used the Newcastle--Ottawa scale to assess methodological bias. We performed subgroup analysis based on sex and WHO region. We quantified heterogeneity with meta-regression and predictive distributions. PROSPERO registration:CRD42016052608.
We identified 6116 studies and included 37. Of 111 258 PLH compared with 10 961 217 HIV-negative participants pooled odds of smoking were 1.64 (95% confidence interval, 95% CI: 1.45-1.85) (95% prediction interval: 0.66-4.10, I2 = 98.1%). Odds for men and women living with HIV were 1.68 (95% CI: 1.44-1.95) (95% prediction interval: 0.71-3.98, I2 = 91.1%) and 2.16 (95% CI: 1.77-2.63) (95% prediction interval: 0.92-5.07, I2 = 81.7%) respectively.
PLH are more likely to be smokers than people without HIV. This finding was true in subgroup analyses of men, women and in four of five WHO regions from which data were available. Meta-regression did not explain heterogeneity, which we attribute to the diversity of PLH populations worldwide. Smoking is a barrier to PLH achieving parity in life expectancy and an important covariate in studies of HIV-associated multimorbidity.
There remains considerable debate over the active form of gold under operating conditions of a recently validated gold catalyst for acetylene hydrochlorination. We have performed an in situ x-ray ...absorption fine structure study of gold/carbon (Au/C) catalysts under acetylene hydrochlorination reaction conditions and show that highly active catalysts comprise single-site cationic Au entities whose activity correlates with the ratio of Au(I):Au(III) present. We demonstrate that these Au/C catalysts are supported analogs of single-site homogeneous Au catalysts and propose a mechanism, supported by computational modeling, based on a redox couple of Au(I)-Au(III) species.
Professor Eric Walker: an appreciation Johnston, Peter W
Journal of pathology,
December 2018, 2018-Dec, 2018-12-00, 20181201, Volume:
246, Issue:
4
Journal Article
Modelling the electrical activity of the heart is an important tool for understanding electrical function in various diseases and conduction disorders. Clearly, for model results to be useful, it is ...necessary to have accurate inputs for the models, in particular the commonly used bidomain model. However, there are only three sets of four experimentally determined conductivity values for cardiac ventricular tissue and these are inconsistent, were measured around 40 years ago, often produce different results in simulations and do not fully represent the three-dimensional anisotropic nature of cardiac tissue. Despite efforts in the intervening years, difficulties associated with making the measurements and also determining the conductivities from the experimental data have not yet been overcome. In this review, we summarise what is known about the conductivity values, as well as progress to date in meeting the challenges associated with both the mathematical modelling and the experimental techniques.
Graphical abstract
Epicardial potential distributions, arising from a subendocardial ischaemic region, modelled using conductivity data from the indicated studies.
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