| 1. |
- Schael, S, et al.
(författare)
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Precision electroweak measurements on the Z resonance
- 2006
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Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Forskningsöversikt (refereegranskat)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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| 2. |
- 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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| 3. |
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| 4. |
- Bridel, Claire, et al.
(författare)
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Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
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Forskningsöversikt (refereegranskat)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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| 5. |
- Frykholm, Peter, 1961-, et al.
(författare)
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Preoperative fasting in children : review of existing guidelines and recent developments
- 2018
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Ingår i: British Journal of Anaesthesia. - : Elsevier BV. - 0007-0912 .- 1471-6771. ; 120:3, s. 469-474
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Forskningsöversikt (refereegranskat)abstract
- The current guidelines for preoperative fasting recommend intervals of 6, 4, and 2 h (6-4-2) of fasting for solids, breast milk, and clear fluids, respectively. The objective is to minimize the risk of pulmonary aspiration of gastric contents, but also to prevent unnecessarily long fasting intervals. Pulmonary aspiration is rare and associated with nearly no mortality in paediatric anaesthesia. The incidence may have decreased during the last decades, judging from several audits published recently. However, several reports of very long fasting intervals have also been published, in spite of the implementation of the 6-4-2 fasting regimens. In this review, we examine the physiological basis for various fasting recommendations, the temporal relationship between fluid intake and residual gastric content, and the pathophysiological effects of preoperative fasting, and review recent publications of various attempts to reduce the incidence of prolonged fasting in children. The pros and cons of the current guidelines will be addressed, and possible strategies for a future revision will be suggested.
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| 6. |
- Brits, Martin, et al.
(författare)
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Critical review of the analysis of brominated flame retardants and their environmental levels in Africa
- 2016
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Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 164, s. 174-189
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Forskningsöversikt (refereegranskat)abstract
- World-wide, the prevalence of brominated flame retardants (BFRs) is well documented for routine analysis of environmental and biological matrices. There is, however, limited information on these compounds in the African environment and insufficient information on the analytical approaches used to obtain data. This paper presents a review on BFR levels in the African environment and the various analytical methodologies specifically applied in Africa for polybrominated diphenyl ethers (PBDEs), polybrominated biphenyls and alternative-BFRs. The analyses include liquid sample preparation using liquid-liquid and solid phase extraction and solid sample preparation involving Soxhlet extraction, with ultrasound-assisted extraction increasingly being applied. Instrumental detection techniques were limited to gas chromatography coupled with electron capture detector and electron impact ionisation with single quadrupole mass spectrometers. Information on congener profile prevalence in indoor dust, soil, aquatic environment (water, sediment, and aquatic organisms), eggs, wastewater treatment plant compartments, landfills (leachate and sediment) and breast milk are presented. Although PBDEs were inconsistently detected, contamination was reported for all investigated matrices in the African environment. The manifestation in remote regions indicates the ubiquitous prevalence and long-range transport of these compounds. Levels in sediment, and breast milk from some African countries were higher than reported for Asia and Europe. Due to limited data or non-detection of alternative-BFRs, it is unclear whether banned formulations were replaced in Africa. Most of the data reported for BFR levels in Africa were obtained in non-African laboratories or in South Africa and formed the basis for our discussion of reported contamination levels and related methodologies.
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| 7. |
- Godoy, Patricio, et al.
(författare)
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Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME
- 2013
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Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 87:8, s. 1315-1530
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Forskningsöversikt (refereegranskat)abstract
- This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro. In a complex architecture of nested, zonated lobules, the liver consists of approximately 80 % hepatocytes and 20 % non-parenchymal cells, the latter being involved in a secondary phase that may dramatically aggravate the initial damage. Hepatotoxicity, as well as hepatic metabolism, is controlled by a set of nuclear receptors (including PXR, CAR, HNF-4 alpha, FXR, LXR, SHP, VDR and PPAR) and signaling pathways. When isolating liver cells, some pathways are activated, e.g., the RAS/MEK/ERK pathway, whereas others are silenced (e.g. HNF-4 alpha), resulting in up- and downregulation of hundreds of genes. An understanding of these changes is crucial for a correct interpretation of in vitro data. The possibilities and limitations of the most useful liver in vitro systems are summarized, including three-dimensional culture techniques, co-cultures with non-parenchymal cells, hepatospheres, precision cut liver slices and the isolated perfused liver. Also discussed is how closely hepatoma, stem cell and iPS cell-derived hepatocyte-like-cells resemble real hepatocytes. Finally, a summary is given of the state of the art of liver in vitro and mathematical modeling systems that are currently used in the pharmaceutical industry with an emphasis on drug metabolism, prediction of clearance, drug interaction, transporter studies and hepatotoxicity. One key message is that despite our enthusiasm for in vitro systems, we must never lose sight of the in vivo situation. Although hepatocytes have been isolated for decades, the hunt for relevant alternative systems has only just begun.
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| 8. |
- Hallett, Lauren M., et al.
(författare)
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Restoration ecology through the lens of coexistence theory
- 2023
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Ingår i: Trends in Ecology & Evolution. - : CELL PRESS. - 0169-5347 .- 1872-8383. ; 38:11, s. 1085-1096
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Forskningsöversikt (refereegranskat)abstract
- Advances in restoration ecology are needed to guide ecological restoration in a variable and changing world. Coexistence theory provides a framework for how variability in environmental conditions and species interactions affects species success. Here, we conceptually link coexistence theory and restoration ecology. First, including low-density growth rates (LDGRs), a classic metric of coexistence, can improve abundance-based restoration goals, because abundances are sensitive to initial treatments and ongoing variability. Second, growth-rate partitioning, developed to identify coexistence mechanisms, can improve restoration practice by informing site selection and indicating necessary interventions (e.g., site amelioration or competitor removal). Finally, coexistence methods can improve restoration assessment, because initial growth rates indicate trajectories, average growth rates measure success, and growth partitioning highlights interventions needed in future.
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| 9. |
- Masterson, C. H., et al.
(författare)
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Mesenchymal stem/stromal cell-based therapies for severe viral pneumonia: therapeutic potential and challenges
- 2021
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Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 9:61, s. 1-21
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Forskningsöversikt (refereegranskat)abstract
- Severe viral pneumonia is a significant cause of morbidity and mortality globally, whether due to outbreaks of endemic viruses, periodic viral epidemics, or the rarer but devastating global viral pandemics. While limited anti-viral therapies exist, there is a paucity of direct therapies to directly attenuate viral pneumonia-induced lung injury, and management therefore remains largely supportive. Mesenchymal stromal/stem cells (MSCs) are receiving considerable attention as a cytotherapeutic for viral pneumonia. Several properties of MSCs position them as a promising therapeutic strategy for viral pneumonia-induced lung injury as demonstrated in pre-clinical studies in relevant models. More recently, early phase clinical studies have demonstrated a reassuring safety profile of these cells. These investigations have taken on an added importance and urgency during the COVID-19 pandemic, with multiple trials in progress across the globe. In parallel with clinical translation, strategies are being investigated to enhance the therapeutic potential of these cells in vivo, with different MSC tissue sources, specific cellular products including cell-free options, and strategies to ‘licence’ or ‘pre-activate’ these cells, all being explored. This review will assess the therapeutic potential of MSC-based therapies for severe viral pneumonia. It will describe the aetiology and epidemiology of severe viral pneumonia, describe current therapeutic approaches, and examine the data suggesting therapeutic potential of MSCs for severe viral pneumonia in pre-clinical and clinical studies. The challenges and opportunities for MSC-based therapies will then be considered.
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| 10. |
- Serenelli, Aldo, et al.
(författare)
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Weighing stars from birth to death : mass determination methods across the HRD
- 2021
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Ingår i: Astronomy and Astrophysics Review. - : Springer Science and Business Media LLC. - 0935-4956 .- 1432-0754. ; 29:1
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Forskningsöversikt (refereegranskat)abstract
- The mass of a star is the most fundamental parameter for its structure, evolution, and final fate. It is particularly important for any kind of stellar archaeology and characterization of exoplanets. There exist a variety of methods in astronomy to estimate or determine it. In this review we present a significant number of such methods, beginning with the most direct and model-independent approach using detached eclipsing binaries. We then move to more indirect and model-dependent methods, such as the quite commonly used isochrone or stellar track fitting. The arrival of quantitative asteroseismology has opened a completely new approach to determine stellar masses and to complement and improve the accuracy of other methods. We include methods for different evolutionary stages, from the pre-main sequence to evolved (super)giants and final remnants. For all methods uncertainties and restrictions will be discussed. We provide lists of altogether more than 200 benchmark stars with relative mass accuracies between [0.3 , 2] % for the covered mass range of M∈[0.1,16]M⊙, 75 % of which are stars burning hydrogen in their core and the other 25 % covering all other evolved stages. We close with a recommendation how to combine various methods to arrive at a “mass-ladder” for stars.
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