| 1. |
- Mathieu, François, et al.
(författare)
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Relationship Between Measures of Cerebrovascular Reactivity and Intracranial Lesion Progression in Acute TBI Patients : an Exploratory Analysis.
- 2020
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Ingår i: Neurocritical Care. - : Springer. - 1541-6933 .- 1556-0961. ; 32:2, s. 373-382
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Failure of cerebral autoregulation and progression of intracranial lesion have both been shown to contribute to poor outcome in patients with acute traumatic brain injury (TBI), but the interplay between the two phenomena has not been investigated. Preliminary evidence leads us to hypothesize that brain tissue adjacent to primary injury foci may be more vulnerable to large fluctuations in blood flow in the absence of intact autoregulatory mechanisms. The goal of this study was therefore to assess the influence of cerebrovascular reactivity measures on radiological lesion expansion in a cohort of patients with acute TBI.METHODS: We conducted a retrospective cohort analysis on 50 TBI patients who had undergone high-frequency multimodal intracranial monitoring and for which at least two brain computed tomography (CT) scans had been performed in the acute phase of injury. We first performed univariate analyses on the full cohort to identify non-neurophysiological factors (i.e., initial lesion volume, timing of scan, coagulopathy) associated with traumatic lesion growth in this population. In a subset analysis of 23 patients who had intracranial recording data covering the period between the initial and repeat CT scan, we then correlated changes in serial volumetric lesion measurements with cerebrovascular reactivity metrics derived from the pressure reactivity index (PRx), pulse amplitude index (PAx), and RAC (correlation coefficient between the pulse amplitude of intracranial pressure and cerebral perfusion pressure). Using multivariate methods, these results were subsequently adjusted for the non-neurophysiological confounders identified in the univariate analyses.RESULTS: We observed significant positive linear associations between the degree of cerebrovascular reactivity impairment and progression of pericontusional edema. The strongest correlations were observed between edema progression and the following indices of cerebrovascular reactivity between sequential scans: % time PRx > 0.25 (r = 0.69, p = 0.002) and % time PAx > 0.25 (r = 0.64, p = 0.006). These associations remained significant after adjusting for initial lesion volume and mean cerebral perfusion pressure. In contrast, progression of the hemorrhagic core and extra-axial hemorrhage volume did not appear to be strongly influenced by autoregulatory status.CONCLUSIONS: Our preliminary findings suggest a possible link between autoregulatory failure and traumatic edema progression, which warrants re-evaluation in larger-scale prospective studies.
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| 2. |
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| 3. |
- Nordberg, Gunnar F, et al.
(författare)
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Risk assessment
- 2015. - 4
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Ingår i: Handbook on the toxicology of metals. - : Academic Press. - 9780123982926 ; , s. 461-486
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Bokkapitel (refereegranskat)abstract
- Risk assessment for metallic substances usually follows the generally accepted framework format for risk assessment for all toxic substances, which involves (1) exposure assessment, (2) hazard identification, (3) assessment of dose-response relationships, and (4) risk characterization. The importance of risk communication is also addressed. Risk assessment/risk communication is of particular relevance for metals and metalloids because all living organisms are exposed to these elements. Lead, cadmium, mercury, and the metalloid arsenic have been responsible for many human poisonings and even deaths. It is, hence, imperative that readers of this Handbook have a firm perspective on the exposure levels of metallic substances that produce adverse health effects and the various risk assessment approaches that have been used and are evolving to protect the health and well-being of living organisms. Because of the increasing use of nanomaterials, a recent concern is the dose metric for inhaled metallic nanoparticles. Regardless of exposure route, the following risk assessment considerations are important: biomonitoring approaches, identification of the mode of action for toxicity of metallic species for hazard identification, determining dose-effect relationships, the construction of dose-response curves, and the development of benchmark doses for various metallic species, which are discussed in relation to protecting sensitive subpopulations because not all individuals within a general population are at equal risk for toxicity. Risk characterization using modern biomarkers that are capable of detecting early cellular effects to low-dose exposures to metallic substances will play an increasingly important role in assessing risk from exposure to this class of toxic substances on an individual or mixture basis. The issue of metal-/metalloid-induced carcinogenesis is of ever increasing importance because many of the elements associated with this cellular outcome produce a number of early cellular effects, including the formation of reactive oxygen species, modification of apoptosis, and methylation of DNA. Finally, the issue of risk communication/risk management is of great importance because these issues are critical to addressing the health concerns of exposed populations and the practical, ethical, and financial issues related to reducing hazardous exposures to metallic substances.
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| 4. |
- Romm, H., et al.
(författare)
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Web-based scoring of the dicentric assay, a collaborative biodosimetric scoring strategy for population triage in large scale radiation accidents
- 2014
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Ingår i: Radiation and Environmental Biophysics. - : Springer Science and Business Media LLC. - 0301-634X .- 1432-2099. ; 53:2, s. 241-254
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Tidskriftsartikel (refereegranskat)abstract
- In the case of a large scale radiation accident high throughput methods of biological dosimetry for population triage are needed to identify individuals requiring clinical treatment. The dicentric assay performed in web-based scoring mode may be a very suitable technique. Within the MULTIBIODOSE EU FP7 project a network is being established of 8 laboratories with expertise in dose estimations based on the dicentric assay. Here, the manual dicentric assay was tested in a web-based scoring mode. More than 23,000 high resolution images of metaphase spreads (only first mitosis) were captured by four laboratories and established as image galleries on the internet (cloud). The galleries included images of a complete dose effect curve (0-5.0 Gy) and three types of irradiation scenarios simulating acute whole body, partial body and protracted exposure. The blood samples had been irradiated in vitro with gamma rays at the University of Ghent, Belgium. Two laboratories provided image galleries from Fluorescence plus Giemsa stained slides (3 h colcemid) and the image galleries from the other two laboratories contained images from Giemsa stained preparations (24 h colcemid). Each of the 8 participating laboratories analysed 3 dose points of the dose effect curve (scoring 100 cells for each point) and 3 unknown dose points (50 cells) for each of the 3 simulated irradiation scenarios. At first all analyses were performed in a QuickScan Mode without scoring individual chromosomes, followed by conventional scoring (only complete cells, 46 centromeres). The calibration curves obtained using these two scoring methods were very similar, with no significant difference in the linear-quadratic curve coefficients. Analysis of variance showed a significant effect of dose on the yield of dicentrics, but no significant effect of the laboratories, different methods of slide preparation or different incubation times used for colcemid. The results obtained to date within the MULTIBIODOSE project by a network of 8 collaborating laboratories throughout Europe are very promising. The dicentric assay in the web based scoring mode as a high throughput scoring strategy is a useful application for biodosimetry in the case of a large scale radiation accident.
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| 5. |
- Sarangi, Sohan, et al.
(författare)
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Segregation in inhalable powders : Quantification of the effect of vibration on adhesive mixtures
- 2023
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Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier. - 0939-6411 .- 1873-3441. ; 187, s. 107-119
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this investigation was to study the effect of induced vibrations on adhesive mixtures containing budesonide and salbutamol sulphate as active pharmaceutical ingredients (APIs) and Inhalacr 70 as carriers. A series of adhesive mixtures with varied fine concentrations (1–4%) was prepared for each API. Half of the adhesive mixture was stressed on a vibrating sieve under conditions resembling hopper flow. Based on scanning electron micrographs, it was concluded that Inhalacr 70 contains particles of two distinct shapes, one irregular with groves and valleys and the other more regular with well-defined edges. The dispersibility of the control and stressed mixtures was studied using a next generation impactor. The stressed mixtures containing 1 and 1.5% API displayed a significant reduction in fine particle dose (FPD) compared to the control. The reduction in FPD resulted from a loss of fines from the adhesive mixture during vibration and as a consequence of restructuring and self-agglomeration resulting in reduced dispersibility. However, no significant difference was observed for mixtures with larger weight fractions of fines (2 and 4% API) but these have a drawback of reduced fine particle fraction (FPF). It is concluded that vibrations induced on the adhesive mixtures during handling potentially have a significant effect on the dispersibility of the API and the total amount of drug delivered to the lungs.
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