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- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 2. |
- Yang, Wen-Yi, et al.
(författare)
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Association of Office and Ambulatory Blood Pressure With Mortality and Cardiovascular Outcomes
- 2019
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Ingår i: Journal of the American Medical Association (JAMA). - : AMER MEDICAL ASSOC. - 0098-7484 .- 1538-3598. ; 322:5, s. 409-420
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Tidskriftsartikel (refereegranskat)abstract
- ImportanceBlood pressure (BP) is a known risk factor for overall mortality and cardiovascular (CV)-specific fatal and nonfatal outcomes. It is uncertain which BP index is most strongly associated with these outcomes. ObjectiveTo evaluate the association of BP indexes with death and a composite CV event. Design, Setting, and ParticipantsLongitudinal population-based cohort study of 11135 adults from Europe, Asia, and South America with baseline observations collected from May 1988 to May 2010 (last follow-ups, August 2006-October 2016). ExposuresBlood pressure measured by an observer or an automated office machine; measured for 24 hours, during the day or the night; and the dipping ratio (nighttime divided by daytime readings). Main Outcomes and MeasuresMultivariable-adjusted hazard ratios (HRs) expressed the risk of death or a CV event associated with BP increments of 20/10 mm Hg. Cardiovascular events included CV mortality combined with nonfatal coronary events, heart failure, and stroke. Improvement in model performance was assessed by the change in the area under the curve (AUC). ResultsAmong 11135 participants (median age, 54.7 years, 49.3% women), 2836 participants died (18.5 per 1000 person-years) and 2049 (13.4 per 1000 person-years) experienced a CV event over a median of 13.8 years of follow-up. Both end points were significantly associated with all single systolic BP indexes (P<.001). For nighttime systolic BP level, the HR for total mortality was 1.23 (95% CI, 1.17-1.28) and for CV events, 1.36 (95% CI, 1.30-1.43). For the 24-hour systolic BP level, the HR for total mortality was 1.22 (95% CI, 1.16-1.28) and for CV events, 1.45 (95% CI, 1.37-1.54). With adjustment for any of the other systolic BP indexes, the associations of nighttime and 24-hour systolic BP with the primary outcomes remained statistically significant (HRs ranging from 1.17 [95% CI, 1.10-1.25] to 1.87 [95% CI, 1.62-2.16]). Base models that included single systolic BP indexes yielded an AUC of 0.83 for mortality and 0.84 for the CV outcomes. Adding 24-hour or nighttime systolic BP to base models that included other BP indexes resulted in incremental improvements in the AUC of 0.0013 to 0.0027 for mortality and 0.0031 to 0.0075 for the composite CV outcome. Adding any systolic BP index to models already including nighttime or 24-hour systolic BP did not significantly improve model performance. These findings were consistent for diastolic BP. Conclusions and RelevanceIn this population-based cohort study, higher 24-hour and nighttime blood pressure measurements were significantly associated with greater risks of death and a composite CV outcome, even after adjusting for other office-based or ambulatory blood pressure measurements. Thus, 24-hour and nighttime blood pressure may be considered optimal measurements for estimating CV risk, although statistically, model improvement compared with other blood pressure indexes was small.
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| 4. |
- Janko, Matthew R., et al.
(författare)
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In-situ bypass is associated with superior infection-free survival compared with extra-anatomic bypass for the management of secondary aortic graft infections without enteric involvement
- 2022
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Ingår i: Journal of Vascular Surgery. - : Elsevier. - 0741-5214 .- 1097-6809. ; 76:2, s. 546-
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The optimal revascularization modality following complete resection of aortic graft infection (AGI) without enteric involvement remains unclear. The purpose of this investigation is to determine the revascularization approach associated with the lowest morbidity and mortality using real-world data in patients undergoing complete excision of AGI. Methods: A retrospective, multi-institutional study of AGI from 2002 to 2014 was performed using a standardized database. Baseline demographics, comorbidities, and perioperative variables were recorded. The primary outcome was infection-free survival. Descriptive statistics, Kaplan-Meier survival analysis, and univariate and multivariable analyses were performed. Results: A total of 241 patients at 34 institutions from seven countries presented with AGI during the study period (median age, 68 years; 75% male). The initial aortic procedures that resulted in AGI were 172 surgical grafts (71%), 66 endografts (27%), and three unknown (2%). Of the patients, 172 (71%) underwent complete excision of infected aortic graft material followed by in situ (in-line) bypass (ISB), including antibiotic-treated prosthetic graft (35%), autogenous femoral vein (neo-aortoiliac surgery) (24%), and cryopreserved allograft (41%). Sixty-nine patients (29%) underwent extra-anatomic bypass (EAB). Overall median Kaplan-Meier estimated survival was 5.8 years. Perioperative mortality was 16%. When stratified by ISB vs EAB, there was a significant difference in Kaplan-Meier estimated infection-free survival (2910 days; interquartile range, 391-3771 days vs 180 days; interquartile range, 27-3750 days; P <.001). There were otherwise no significant differences in presentation, comorbidities, or perioperative variables. Multivariable Cox regression showed lower infection-free survival among patients with EAB (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.6-3.6; P <.001), polymicrobial infection (HR, 2.2; 95% CI, 1.4-3.5; P = .001), methicillin-resistant Staphylococcus aureus infection (HR, 1.7; 95% CI, 1.1-2.7; P = .02), as well as the protective effect of omental/muscle flap coverage (HR, 0.59; 95% CI, 0.37-0.92; P = .02). Conclusions: After complete resection of AGI, perioperative mortality is 16% and median overall survival is 5.8 years. EAB is associated with nearly a two and one-half-fold higher reinfection/mortality compared with ISB. Omental and/or muscle flap coverage of the repair appear protective.
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| 11. |
- Neuhausen, J., et al.
(författare)
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Properties of irradiated LBE and Pb
- 2015
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Ingår i: Handbook on Lead-bismuth Eutectic Alloy and Lead Properties, Materials Compatibility, Thermal-hydraulics and Technologies - 2015 Edition (NEA-7268). - : Nuclear Energy Agency of the OECD (NEA).
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 12. |
- Pemunta, Ngambouk Vitalis, 1973-, et al.
(författare)
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Toward a reconceptualization of the “urban” and “rural” as conceptual and analytical categories in the social sciences
- 2012
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Ingår i: Arts and Social Sciences Journal. - : Aston Journals. - 2151-6200. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Globalization implies a general shift in spatio-temporal relations and the simultaneous deterritorialization of cultural phenomena orchestrated by the multiple global flows of people, ideas, and fashions. Within the context of globalization, it is troublesome for social scientists to continue using the “urban–rural” dichotomy as distinctive analytical and methodological categories because it tends to suggest a contingency in the pattern and character of social phenomena. This article sets out to theoretically rethink this conceptualization because of the multi-stranded and culturally embedded nature of human behavior in both space and time which has led to difficulties in delineating rigid subject boundaries today unlike in the past. Drawing on empirical data from diverse social phenomena, but particularly from the urban procurement and consumption of medicinal plant recipes, “dualistic” religious inclination and urban agriculture, we demonstrate that the geographic, spatio-temporal conceptualization of distinctive urban and rural phenomena are problematic. We suggest the notions of “urban-ruralism” and “rural-urbanism” as theoretical and methodological reconceptualizations to capture multiple embedded processes and to show that there exists a type of behavioral continuum/consistency because individuals have adopted hyphenated identities.
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| 13. |
- Schrijver, Carolus J., et al.
(författare)
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Understanding space weather to shield society : A global road map for 2015-2025 commissioned by COSPAR and ILWS
- 2015
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Ingår i: Advances in Space Research. - : Elsevier BV. - 0273-1177 .- 1879-1948. ; 55:12, s. 2745-2807
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Tidskriftsartikel (refereegranskat)abstract
- There is a growing appreciation that the environmental conditions that we call space weather impact the technological infrastructure that powers the coupled economies around the world. With that comes the need to better shield society against space weather by improving forecasts, environmental specifications, and infrastructure design. We recognize that much progress has been made and continues to be made with a powerful suite of research observatories on the ground and in space, forming the basis of a Sun Earth system observatory. But the domain of space weather is vast extending from deep within the Sun to far outside the planetary orbits and the physics complex including couplings between various types of physical processes that link scales and domains from the microscopic to large parts of the solar system. Consequently, advanced understanding of space weather requires a coordinated international approach to effectively provide awareness of the processes within the Sun Earth system through observation-driven models. This roadmap prioritizes the scientific focus areas and research infrastructure that are needed to significantly advance our understanding of space weather of all intensities and of its implications for society. Advancement of the existing system observatory through the addition of small to moderate state-of-the-art capabilities designed to fill observational gaps will enable significant advances. Such a strategy requires urgent action: key instrumentation needs to be sustained, and action needs to be taken before core capabilities are lost in the aging ensemble. We recommend advances through priority focus (1) on observation-based modeling throughout the Sun Earth system, (2) on forecasts more than 12 h ahead of the magnetic structure of incoming coronal mass ejections, (3) on understanding the geospace response to variable solar-wind stresses that lead to intense geomagnetically-induced currents and ionospheric and radiation storms, and (4) on developing a comprehensive specification of space climate, including the characterization of extreme space storms to guide resilient and robust engineering of technological infrastructures. The roadmap clusters its implementation recommendations by formulating three action pathways, and outlines needed instrumentation and research programs and infrastructure for each of these. An executive summary provides an overview of all recommendations.
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