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- Flachskampf, Frank A, et al.
(författare)
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Overestimation of flow velocity through leaks in mechanical valve prostheses and through small orifices by continuous-wave Doppler.
- 1997
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Ingår i: Journal of the American Society of Echocardiography. - 0894-7317 .- 1097-6795. ; 10:9, s. 904-914
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Tidskriftsartikel (refereegranskat)abstract
- The reliability of continuous-wave Doppler flow velocity measurements through small regurgitant lesions, such as in prosthetic leakage, has not been systematically analyzed. To evaluate the accuracy of continuous-wave Doppler in prosthetic valve leakage and small orifices in an in vitro, steady-flow model-flow velocities through the leaks of twelve intact mechanical prostheses and through six circular nozzles (area 0.5 to 20 mm2) were measured at pressure drops between 30 and 105 mm Hg. These results were compared with those predicted by the modified Bernoulli equation. Laser Doppler anemometry of flow velocities through the nozzles was also performed. Despite high correlation, there was substantial overestimation of Bernoulli predicted velocities by echo Doppler in the prosthetic leaks (mean +12.3% +/- 9.4%; range 90.3% to 143.4%). In the nozzles < or = 10 mm2, but not in the largest (20 mm2) nozzle, there was also overestimation of the Bernoulli predicted velocities (mean +6.2% +/- 2%). Laser Doppler anemometry of flow velocities through the nozzles showed slightly lower values than predicted by the Bernoulli equation. Thus, continuous-wave echo Doppler overestimates flow velocities through small orifices. This apparently is, at least in part, due to transit time effects and should be taken into account when using echo Doppler in small (< 10 mm2) orifices, such as in mild to moderate regurgitant lesions and prosthetic valve leakage.
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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 in higher eukaryotes
- 2008
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Ingår i: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
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Forskningsöversikt (refereegranskat)abstract
- Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is 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 verify an autophagic response.
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- Paiva Fonseca, Gabriel, et al.
(författare)
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Dose specification for Ir-192 high dose rate brachytherapy in terms of dose-to-water-in-medium and dose-to-medium-in-medium
- 2015
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing: Hybrid Open Access. - 0031-9155 .- 1361-6560. ; 60:11, s. 4565-4579
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Tidskriftsartikel (refereegranskat)abstract
- Dose calculation in high dose rate brachytherapy with Ir-192 is usually based on the TG-43U1 protocol where all media are considered to be water. Several dose calculation algorithms have been developed that are capable of handling heterogeneities with two possibilities to report dose: dose-to-medium-inmedium (D-m,D-m) and dose-to-water-in-medium (D-w,D-m). The relation between D-m,D-m and D-w,D-m for Ir-192 is the main goal of this study, in particular the dependence of D-w,D-m on the dose calculation approach using either large cavity theory (LCT) or small cavity theory (SCT). A head and neck case was selected due to the presence of media with a large range of atomic numbers relevant to tissues and mass densities such as air, soft tissues and bone interfaces. This case was simulated using a Monte Carlo (MC) code to score: D-m,D-m, D-w,D-m (LCT), mean photon energy and photon fluence. D-w,D-m (SCT) was derived from MC simulations using the ratio between the unrestricted collisional stopping power of the actual medium and water. Differences between D-m,D-m and D-w,D-m (SCT or LCT) can be negligible (less than1%) for some tissues e.g. muscle and significant for other tissues with differences of up to 14% for bone. Using SCT or LCT approaches leads to differences between D-w,D-m (SCT) and D-w,D-m (LCT) up to 29% for bone and 36% for teeth. The mean photon energy distribution ranges from 222 keV up to 356 keV. However, results obtained using mean photon energies are not equivalent to the ones obtained using the full, local photon spectrum. This work concludes that it is essential that brachytherapy studies clearly report the dose quantity. It further shows that while differences between D-m,D-m and D-w,D-m (SCT) mainly depend on tissue type, differences between D-m,D-m and D-w,D-m (LCT) are, in addition, significantly dependent on the local photon energy fluence spectrum which varies with distance to implanted sources.
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- Pardiñas, Antonio F., et al.
(författare)
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Interaction Testing and Polygenic Risk Scoring to Estimate the Association of Common Genetic Variants With Treatment Resistance in Schizophrenia
- 2022
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Ingår i: JAMA psychiatry. - Chicago, IL, United States : American Medical Association. - 2168-6238 .- 2168-622X. ; 79:3, s. 260-269
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Tidskriftsartikel (refereegranskat)abstract
- Importance About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schizophrenia are largely unknown. Adequately powered genetic studies of TRS are scarce because of the difficulty in collecting data from well-characterized TRS cohorts.Objective To examine the genetic architecture of TRS through the reassessment of genetic data from schizophrenia studies and its validation in carefully ascertained clinical samples.Design, Setting, and Participants Two case-control genome-wide association studies (GWASs) of schizophrenia were performed in which the case samples were defined as individuals with TRS (n = 10 501) and individuals with non-TRS (n = 20 325). The differences in effect sizes for allelic associations were then determined between both studies, the reasoning being such differences reflect treatment resistance instead of schizophrenia. Genotype data were retrieved from the CLOZUK and Psychiatric Genomics Consortium (PGC) schizophrenia studies. The output was validated using polygenic risk score (PRS) profiling of 2 independent schizophrenia cohorts with TRS and non-TRS: a prevalence sample with 817 individuals (Cardiff Cognition in Schizophrenia [CardiffCOGS]) and an incidence sample with 563 individuals (Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances [STRATA-G]).Main Outcomes and Measures GWAS of treatment resistance in schizophrenia. The results of the GWAS were compared with complex polygenic traits through a genetic correlation approach and were used for PRS analysis on the independent validation cohorts using the same TRS definition.Results The study included a total of 85 490 participants (48 635 [56.9%] male) in its GWAS stage and 1380 participants (859 [62.2%] male) in its PRS validation stage. Treatment resistance in schizophrenia emerged as a polygenic trait with detectable heritability (1% to 4%), and several traits related to intelligence and cognition were found to be genetically correlated with it (genetic correlation, 0.41-0.69). PRS analysis in the CardiffCOGS prevalence sample showed a positive association between TRS and a history of taking clozapine (r2 = 2.03%; P = .001), which was replicated in the STRATA-G incidence sample (r2 = 1.09%; P = .04).Conclusions and Relevance In this GWAS, common genetic variants were differentially associated with TRS, and these associations may have been obscured through the amalgamation of large GWAS samples in previous studies of broadly defined schizophrenia. Findings of this study suggest the validity of meta-analytic approaches for studies on patient outcomes, including treatment resistance.
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