IEEE recently introduced new revisions to the medium- and high-voltage circuit breaker standards. The revised standards provide for new ratings and capabilities; expand choices for users by making it ...easier to certify and accept under IEEE/ANSI standards equipment originally destined for the IEC market; and clarify the scope and limitations of various ratings of importance to the industrial user. This article presents some of the more pertinent changes and how these changes affect the application of circuit breakers in the petroleum and chemical industries.
Abstract Objective As a negative regulator of T cells, Programmed Death Ligand 1 (PD-L1) is both an indicator and inhibitor of anti -tumor immune responses, which has led to confusion about its ...prognostic significance. We investigated the primary source of PD-L1 expression in epithelial ovarian cancer and its relationship to tumor-infiltrating lymphocytes (TIL) and associated gene products. Methods Tissue microarrays containing high-grade serous carcinomas (HGSC) and endometrioid, clear cell and mucinous ovarian cancers from optimally debulked patients were assessed by immunohistochemistry for expression of PD-L1 and other markers (CD68, CD3, CD8, PD-1, CD103, FoxP3 and CD25). The Cancer Genome Atlas was interrogated for associations between PD-L1 expression and immune-related transcriptional and genomic features of HGSC. Results PD-L1 was primarily expressed by tumor-associated CD68+ macrophages rather than tumor cells. PD-L1+ cells frequently co-localized with CD8, CD4 and PD-1+ TIL, CD25+ FoxP3+ Tregs, and other TIL subsets. PD-L1+ cells were prognostically favorable in HGSC. Moreover, the presence of both PD-L1+ cells and CD8 TIL was associated with better prognosis than CD8 TIL alone. PD-L1 gene expression was independent of BRCA status. At the transcriptional level, PD-L1 was associated with both cytolytic (granzyme B, T-bet and IFN-γ) and suppressive (PD-1, CTLA-4, LAG3 and IDO-1) gene products. Conclusions PD-L1 is primarily expressed by macrophages in ovarian cancer and is strongly associated with both cytolytic and regulatory TIL subsets, resulting in a net positive association with survival. Tumors containing PD-L1+ macrophages appear caught in an immunological stalemate that may require multi-pronged immunotherapy to alleviate.
Abstract
Aims
The Valve Academic Research Consortium (VARC), founded in 2010, was intended to (i) identify appropriate clinical endpoints and (ii) standardize definitions of these endpoints for ...transcatheter and surgical aortic valve clinical trials. Rapid evolution of the field, including the emergence of new complications, expanding clinical indications, and novel therapy strategies have mandated further refinement and expansion of these definitions to ensure clinical relevance. This document provides an update of the most appropriate clinical endpoint definitions to be used in the conduct of transcatheter and surgical aortic valve clinical research.
Methods and results
Several years after the publication of the VARC-2 manuscript, an in-person meeting was held involving over 50 independent clinical experts representing several professional societies, academic research organizations, the US Food and Drug Administration (FDA), and industry representatives to (i) evaluate utilization of VARC endpoint definitions in clinical research, (ii) discuss the scope of this focused update, and (iii) review and revise specific clinical endpoint definitions. A writing committee of independent experts was convened and subsequently met to further address outstanding issues. There were ongoing discussions with FDA and many experts to develop a new classification schema for bioprosthetic valve dysfunction and failure. Overall, this multi-disciplinary process has resulted in important recommendations for data reporting, clinical research methods, and updated endpoint definitions. New definitions or modifications of existing definitions are being proposed for repeat hospitalizations, access site-related complications, bleeding events, conduction disturbances, cardiac structural complications, and bioprosthetic valve dysfunction and failure (including valve leaflet thickening and thrombosis). A more granular 5-class grading scheme for paravalvular regurgitation (PVR) is being proposed to help refine the assessment of PVR. Finally, more specific recommendations on quality-of-life assessments have been included, which have been targeted to specific clinical study designs.
Conclusions
Acknowledging the dynamic and evolving nature of less-invasive aortic valve therapies, further refinements of clinical research processes are required. The adoption of these updated and newly proposed VARC-3 endpoints and definitions will ensure homogenous event reporting, accurate adjudication, and appropriate comparisons of clinical research studies involving devices and new therapeutic strategies.
Graphical Abstract
Surgical aortic valve replacement (SAVR) has long been the mainstay of therapy for severe aortic stenosis. However, transcatheter aortic valve replacement (TAVR) is now generally accepted as the new ...standard of care for patients with symptomatic aortic stenosis who are not candidates for open surgery. Arguably TAVR may also be a preferred alternative to SAVR in carefully selected high-risk, but still operable, patients in whom morbidity and mortality may be reduced. Although TAVR outcomes continue to improve, concerns remain with respect to vascular injury, stroke, paravalvular regurgitation, and valve durability. However, it seems likely that with ongoing refinement of transcatheter valve systems, techniques, and patient selection TAVR is becoming an increasingly appealing option for a much broader range of patients. Randomized trials and ongoing surveillance will play an important role as we enter a new era of rigorous clinical evaluation for minimally invasive therapies for structural heart disease.
ABSTRACT
Searches for space–time variations of fundamental constants have entered an era of unprecedented precision. New, high-quality quasar spectra require increasingly refined analytical methods. ...In this paper, a continuation in a series to establish robust and unbiased methodologies, we explore how convergence criteria in non-linear least-squares optimization impact on quasar absorption system measurements of the fine structure constant α. Given previous claims for high-precision constraints, we critically examine the veracity of a so-called blinding approach, in which α is fixed at the terrestrial value during the model building process, releasing it as a free parameter only after the ‘final’ absorption system kinematic structure has been obtained. We show that this approach results in such small consecutive parameter steps during minimization that convergence is unlikely to be reached, even after as many as 1000 iterations. The fix is straightforward: α must be treated as a free parameter from the earliest possible stages of absorption system model building. The implication of the results presented here is that all previous measurements that have used initially fixed α should be reworked.
Transcatheter aortic valve implantation in 2017: state of the art Barbanti, Marco; Webb, John G; Gilard, Martine ...
EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology,
09/2017, Letnik:
13, Številka:
AA
Journal Article
Recenzirano
In the last 15 years, transcatheter aortic valve implantation (TAVI) technology has met with rapid uptake, with >350,000 procedures performed in >70 countries. Over the same period, this technique ...has evolved from a challenging intervention to a standardised, simple, and streamlined procedure. The purpose of this review article is to provide an overview on the rapidly changing field of TAVI therapy, exploring past achievements, current issues and future perspectives. The discussion has been subdivided into three sections: 1) the evolution of clinical and anatomical indications for TAVI, 2) the description of procedural advances and complication rate trends over time, and 3) the progressive adoption of a minimalist approach.
Objectives The purpose of this study was to investigate the 5-year outcome following transcatheter aortic valve implantation (TAVI). Background Little is known about long-term outcomes following ...TAVI. Methods The 5-year outcomes following successful TAVI with a balloon-expandable valve were evaluated in 88 patients. Patients who died within 30 days after TAVI were excluded. Results Mean aortic valve gradient decreased from 46 ± 18 mm Hg to 10 ± 4.5 mm Hg after TAVI and 11.8 ± 5.7 mm Hg at 5 years (p for post-TAVI trend = 0.06). Mean aortic valve area increased from 0.62 ± 0.17 cm2 to 1.67 ± 0.41 cm2 after TAVI and 1.40 ± 0.25 cm2 at 5 years (p for post-TAVI trend <0.01). At 5 years, 3 patients (3.4%) had moderate prosthetic valve dysfunction (moderate transvalvular regurgitation in 1, moderate stenosis in 1, and moderate mixed disease in 1). Survival rates at 1 to 5 years were 83%, 74%, 53%, 42%, and 35%, respectively. Median survival time after TAVI was 3.4 years (95% confidence interval CI: 2.6 to 4.3), and the risk of death was significantly increased in patients with chronic obstructive pulmonary disease (adjusted hazard ratio HR: 2.17; 95% CI: 1.28 to 3.70) and at least moderate paravalvular regurgitation (adjusted HR: 2.98; 95% CI: 1.44 to 6.17). Conclusions Our study demonstrated favorable long-term outcomes after TAVI. Signs of moderate prosthetic valve failure were observed in 3.4% of patients. No patients developed severe prosthetic regurgitation or stenosis. Comorbidities, notably chronic lung disease and at least moderate paravalvular regurgitation, were associated with reduced long-term survival.
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