52 resultados para thrombolysis time window


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Human resources managers often use assessment centers to evaluate candidates for a job position. During an assessment center, the candidates perform a series of exercises. The exercises require one or two assessors (e.g., managers or psychologists) that observe and evaluate the candidate. If an exercise is designed as a role-play, an actor is required as well which plays, e.g., an unhappy customer with whom the candidate has to deal with. Besides performing the exercises, the candidates have a lunch break within a prescribed time window. Each candidate should be observed by approximately half the number of the assessors. Moreover, an assessor cannot be assigned to a candidate if they personally know each other. The planning problem consists of determining (1) resource-feasible start times of all exercises and lunch breaks and (2) a feasible assignment of assessors to candidates, such that the assessment center duration is minimized. We propose a list-scheduling heuristic that generates feasible schedules for such assessment centers. We develop novel procedures for devising an appropriate scheduling list and for incorporating the problem-specific constraints. Our computational results indicate that our approach is capable of devising optimal or near-optimal solutions to real-world instances within short CPU time.

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Linear- and unimodal-based inference models for mean summer temperatures (partial least squares, weighted averaging, and weighted averaging partial least squares models) were applied to a high-resolution pollen and cladoceran stratigraphy from Gerzensee, Switzerland. The time-window of investigation included the Allerød, the Younger Dryas, and the Preboreal. Characteristic major and minor oscillations in the oxygen-isotope stratigraphy, such as the Gerzensee oscillation, the onset and end of the Younger Dryas stadial, and the Preboreal oscillation, were identified by isotope analysis of bulk-sediment carbonates of the same core and were used as independent indicators for hemispheric or global scale climatic change. In general, the pollen-inferred mean summer temperature reconstruction using all three inference models follows the oxygen-isotope curve more closely than the cladoceran curve. The cladoceran-inferred reconstruction suggests generally warmer summers than the pollen-based reconstructions, which may be an effect of terrestrial vegetation not being in equilibrium with climate due to migrational lags during the Late Glacial and early Holocene. Allerød summer temperatures range between 11 and 12°C based on pollen, whereas the cladoceran-inferred temperatures lie between 11 and 13°C. Pollen and cladocera-inferred reconstructions both suggest a drop to 9–10°C at the beginning of the Younger Dryas. Although the Allerød–Younger Dryas transition lasted 150–160 years in the oxygen-isotope stratigraphy, the pollen-inferred cooling took 180–190 years and the cladoceran-inferred cooling lasted 250–260 years. The pollen-inferred summer temperature rise to 11.5–12°C at the transition from the Younger Dryas to the Preboreal preceded the oxygen-isotope signal by several decades, whereas the cladoceran-inferred warming lagged. Major discrepancies between the pollen- and cladoceran-inference models are observed for the Preboreal, where the cladoceran-inference model suggests mean summer temperatures of up to 14–15°C. Both pollen- and cladoceran-inferred reconstructions suggest a cooling that may be related to the Gerzensee oscillation, but there is no evidence for a cooling synchronous with the Preboreal oscillation as recorded in the oxygen-isotope record. For the Gerzensee oscillation the inferred cooling was ca. 1 and 0.5°C based on pollen and cladocera, respectively, which lies well within the inherent prediction errors of the inference models.

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Referred to as orthographic depth, the degree of consistency of grapheme/phoneme correspondences varies across languages from high in shallow orthographies to low in deep orthographies. The present study investigates the impact of orthographic depth on reading route by analyzing evoked potentials to words in a deep (French) and shallow (German) language presented to highly proficient bilinguals. ERP analyses to German and French words revealed significant topographic modulations 240-280ms post-stimulus onset, indicative of distinct brain networks engaged in reading over this time window. Source estimations revealed that these effects stemmed from modulations of left insular, inferior frontal and dorsolateral regions (German>French) previously associated to phonological processing. Our results show that reading in a shallow language was associated to a stronger engagement of phonological pathways than reading in a deep language. Thus, the lexical pathways favored in word reading are reinforced by phonological networks more strongly in the shallow than deep orthography.

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Intravital imaging has revealed that T cells change their migratory behavior during physiological activation inside lymphoid tissue. Yet, it remains less well investigated how the intrinsic migratory capacity of activated T cells is regulated by chemokine receptor levels or other regulatory elements. Here, we used an adjuvant-driven inflammation model to examine how motility patterns corresponded with CCR7, CXCR4, and CXCR5 expression levels on ovalbumin-specific DO11.10 CD4(+) T cells in draining lymph nodes. We found that while CCR7 and CXCR4 surface levels remained essentially unaltered during the first 48-72 h after activation of CD4(+) T cells, their in vitro chemokinetic and directed migratory capacity to the respective ligands, CCL19, CCL21, and CXCL12, was substantially reduced during this time window. Activated T cells recovered from this temporary decrease in motility on day 6 post immunization, coinciding with increased migration to the CXCR5 ligand CXCL13. The transiently impaired CD4(+) T cell motility pattern correlated with increased LFA-1 expression and augmented phosphorylation of the microtubule regulator Stathmin on day 3 post immunization, yet neither microtubule destabilization nor integrin blocking could reverse TCR-imprinted unresponsiveness. Furthermore, protein kinase C (PKC) inhibition did not restore chemotactic activity, ruling out PKC-mediated receptor desensitization as mechanism for reduced migration in activated T cells. Thus, we identify a cell-intrinsic, chemokine receptor level-uncoupled decrease in motility in CD4(+) T cells shortly after activation, coinciding with clonal expansion. The transiently reduced ability to react to chemokinetic and chemotactic stimuli may contribute to the sequestering of activated CD4(+) T cells in reactive peripheral lymph nodes, allowing for integration of costimulatory signals required for full activation.

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Ischemic complications during aneurysm surgery are a frequent cause of postoperative infarctions and new neurological deficits. In this article, we discuss imaging and neurophysiological tools that may help the surgeon to detect intraoperative ischemia. The strength of intraoperative digital subtraction angiography (DSA) is the full view of the arterial and venous vessel. DSA is the gold standard in complex and giant aneurysms, but due to certain disadvantages, it cannot be considered standard of care. Microvascular Doppler sonography is probably the fastest diagnostic tool and can quickly aid diagnosis of large vessel occlusions. Intraoperative indocyanine green videoangiography is the best tool to assess flow in perforating and larger arteries, as well as occlusion of the aneurysm sac. Intraoperative neurophysiological monitoring with somatosensory and motor evoked potentials indirectly measures blood flow by recording neuronal function. It covers all causes of intraoperative ischemia, provided that ischemia occurs in the brain areas under surveillance. However, every method has advantages and disadvantages. No single method is superior to the others in every aspect. Therefore, it is very important for the neurosurgeon to know the strengths and weaknesses of each tool in order to have them available, to know how to use them for each individual situation, and to be ready to apply them within the time window for reversible cerebral ischemia.

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The population mixing hypothesis proposes that childhood leukaemia (CL) might be a rare complication of a yet unidentified subclinical infection. Large population influxes into previously isolated rural areas may foster localised epidemics of the postulated infection causing a subsequent increase of CL. While marked population growth after a period of stability was central to the formulation of the hypothesis and to the early studies on population mixing, there is a lack of objective criteria to define such growth patterns. We aimed to determine whether periods of marked population growth coincided with increases in the risk of CL in Swiss municipalities. We identified incident cases of CL aged 0-15 years for the period 1985-2010 from the Swiss Childhood Cancer Registry. Annual data on population counts in Swiss municipalities were obtained for 1980-2010. As exposures, we defined (1) cumulative population growth during a 5-year moving time window centred on each year (1985-2010) and (2) periods of 'take-off growth' identified by segmented linear regression. We compared CL incidence across exposure categories using Poisson regression and tested for effect modification by degree of urbanisation. Our study included 1500 incident cases and 2561 municipalities. The incident rate ratio (IRR) comparing the highest to the lowest quintile of 5-year population growth was 1.18 (95 % CI 0.96, 1.46) in all municipalities and 1.33 (95 % CI 0.93, 1.92) in rural municipalities (p value interaction 0.36). In municipalities with take-off growth, the IRR comparing the take-off period (>6 % annual population growth) with the initial period of low or negative growth (<2 %) was 2.07 (95 % CI 0.95, 4.51) overall and 2.99 (1.11, 8.05) in rural areas (p interaction 0.52). Our study provides further support for the population mixing hypothesis and underlines the need to distinguish take-off growth from other growth patterns in future research.

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One in five strokes affects the posterior circulation. Diagnosing posterior circulation stroke can be challenging, as the vascular anatomy can be variable, and because presenting symptoms are often non-specific and fluctuating. Nevertheless, making the correct diagnosis is important, as these strokes have a high chance of recurrence, can be life threatening, and can lead to equally life-threatening complications. Investigation and management largely follow those for stroke in general, although some specific differences exist. These include the preferred use of MRI for diagnosing posterior fossa lesions, the management of basilar artery thrombosis, which may have a longer time window for recanalisation therapy, and the use of endovascular therapies for secondary prevention, which, so far, have not shown any benefit in the treatment of vertebral or basilar artery stenosis. In this review, we summarise the anatomy, aetiology and presentation of posterior circulation stroke, and discuss current approaches to management.

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Guidelines recommend intravenous thrombolysis (IVT) to be applied as early as possible in ischemic stroke (IS), while clinical presentation is often assessed by using the National Institutes of Health Stroke Scale (NIHSS). However, diagnostic workup under time pressure bears the risk of misdiagnosis. Little is known about whether NIHSS could help to differentiate between IS and stroke mimics (SM) in patients being evaluated for IVT.

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BACKGROUND AND PURPOSE: The effect of thrombolysis depends on the time from stroke onset to treatment and therefore also on the time when patients come to the hospital. This study was designed to analyze the variables that influence the time from symptom onset to admission (TTA) to the stroke unit. METHODS: We evaluated the medical records of 615 consecutive stroke or transient ischemic attack (TIA) patients admitted to our neurological department within 48 hours after symptom onset. RESULTS: The median TTA was 180 minutes. Referral by emergency medical services (EMS; P<0.001), high National Institutes of Health Stroke Scale (NIHSS) scores (P<0.001), strokes in the carotid territory (P<0.001), and strokes not attributable to small vessel disease (P<0.001) were associated with shorter prehospital delays. The TTA was adjusted for travel times (adjTTA), and all these variables remained significantly associated with time to admission. In addition, patients with previous experience with stroke or TIA had longer adjTTA (P=0.028). Regression analysis confirmed the independent association between referral by EMS (P=0.010), high NIHSS scores (P<0.001), carotid territory stroke (P<0.001), and first-ever cerebrovascular event (P=0.022) with shorter adjTTA. CONCLUSIONS: Factors such as NIHSS scores and stroke location influence the time to admission but, unlike referral pathways, cannot be modified. Educational programs and stroke campaigns should therefore not only teach typical and less common stroke symptoms and signs but also that EMS provides the fastest means of transportation to a stroke unit and the best chances to get treatment early.

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BACKGROUND AND PURPOSE: It is unclear whether intraarterial (IAT) or intravenous (IVT) thrombolysis is more effective for ischemic stroke with hyperdense middle cerebral artery sign (HMCAS) on computed tomography (CT). The aim of this study was to compare IAT and IVT in stroke patients with HMCAS. METHODS: Comparison of data from 2 stroke units with similar management of stroke associated with HMCAS, except that 1 unit performed IAT with urokinase and the other IVT with plasminogen activator. Time to treatment was up to 6 hours for IAT and up to 3 hours for IVT. Outcome was measured by mortality and the modified Rankin Scale (mRS), dichotomized at 3 months into favorable (mRS 0 to 2) and unfavorable (mRS 3 to 6). RESULTS: One hundred twelve patients exhibited a HMCAS, 55 of 268 patients treated with IAT and 57 of 249 patients who underwent IVT. Stroke severity at baseline and patient age were similar in both groups. Mean time to treatment was longer in the IAT group (244+/-63 minutes) than in the IVT group (156+/-21 minutes; P=0.0001). However, favorable outcome was more frequent after IAT (n=29, 53%) than after IVT (n=13, 23%; P=0.001), and mortality was lower after IAT (n=4, 7%) than after IVT (n=13, 23%; P=0.022). After multiple regression analysis IAT was associated with a more favorable outcome than IVT (P=0.003) but similar mortality (P=0.192). CONCLUSIONS: In this observational study intraarterial thrombolysis was more beneficial than IVT in the specific group of stroke patients presenting with HMCAS on CT, even though IAT was started later. Our results indicate that a randomized trial comparing both thrombolytic treatments in patients with middle cerebral artery occlusion is warranted.

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BACKGROUND: The PROACT II trial showed that intra-arterial thrombolysis (IAT) is effective for treatment of acute ischaemic stroke attributable to M1 and M2 segment occlusions. Incidence of symptomatic intracranial haemorrhage (sICH) was 10%. OBJECTIVE: To evaluate the risk and predictors of sICH after IAT by using urokinase in a large number of patients presenting with the whole spectrum of cerebral vessel occlusions. METHODS: 294 patients with stroke treated with intra-arterial urokinase were retrospectively analysed. The risk of sICH as well as bleeding characteristics were assessed. Demographic and radiological data, time to treatment, urokinase dose, recanalisation rates, stroke aetiology and severity were analysed for predictors. RESULTS: sICH occurred in 14 of 294 (4.8%) patients. The median National Institute of Health Stroke Scale score of all patients was 15. All but one sICH were located in the infarcted brain tissue, and no sICH occurred in patients with peripheral vessel occlusions (M3 or M4 segments of the middle cerebral artery). Poor collaterals (p = 0.001), early signs of ischaemia on computed tomography (p = 0.003), higher urokinase dose (p = 0.019), lower recanalisation rate (p = 0.02) and higher diastolic blood pressure on admission (p = 0.04) were found to be correlated with sICH on univariate analysis. On multivariate analysis, poor collaterals (p = 0.004), urokinase dose (p = 0.021) and early signs on computed tomography (p = 0.026) remained predictors of sICH. CONCLUSIONS: With regard to the whole spectrum of cerebral vessel occlusions, an incidence of <5% sICH after IAT is distinctly low. This result underlines the important role of IAT in the treatment of acute stroke.

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The optimal temporal window of intravenous (IV) computed tomography (CT) cholangiography was prospectively determined. Fifteen volunteers (eight women, seven men; mean age, 38 years) underwent dynamic CT cholangiography. Two unenhanced images were acquired at the porta hepatis. Starting 5 min after initiation of IV contrast infusion (20 ml iodipamide meglumine 52%), 15 pairs of images at 5-min intervals were obtained. Attenuation of the extrahepatic bile duct (EBD) and the liver parenchyma was measured. Two readers graded visualization of the higher-order biliary branches. The first biliary opacification in the EBD occurred between 15 and 25 min (mean, 22.3 min +/- 3.2) after initiation of the contrast agent. Biliary attenuation plateaued between the 35- and the 75-min time points. Maximum hepatic parenchymal enhancement was 18.5 HU +/- 2.7. Twelve subjects demonstrated poor or non-visualization of higher-order biliary branches; three showed good or excellent visualization. Body weight and both biliary attenuation and visualization of the higher-order biliary branches correlated significantly (P<0.05). For peak enhancement of the biliary tree, CT cholangiography should be performed no earlier than 35 min after initiation of IV infusion. For a fixed contrast dose, superior visualization of the biliary system is achieved in subjects with lower body weight.

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PURPOSE: To prospectively determine quantitatively and qualitatively the timing of maximal enhancement of the normal small-bowel wall by using contrast material-enhanced multi-detector row computed tomography (CT). MATERIALS AND METHODS: This HIPAA-compliant study was approved by the institutional review board. After information on radiation risk was given, written informed consent was obtained from 25 participants with no history of small-bowel disease (mean age, 58 years; 19 men) who had undergone single-level dynamic CT. Thirty seconds after the intravenous administration of contrast material, a serial dynamic acquisition, consisting of 10 images obtained 5 seconds apart, was performed. Enhancement measurements were obtained over time from the small-bowel wall and the aorta. Three independent readers qualitatively assessed small-bowel conspicuity. Quantitative and qualitative data were analyzed during the arterial phase, the enteric phase (which represented peak small-bowel mural enhancement), and the venous phase. Statistical analysis included paired Student t test and Wilcoxon signed rank test with Bonferroni correction. A P value less than .05 was used to indicate a significant difference. RESULTS: The mean time to peak enhancement of the small-bowel wall was 49.3 seconds +/- 7.7 (standard deviation) and 13.5 seconds +/- 7.6 after peak aortic enhancement. Enhancement values were highest during the enteric phase (P < .05). Regarding small-bowel conspicuity, images obtained during the enteric phase were most preferred qualitatively; there was a significant difference between the enteric and arterial phases (P < .001) but not between the enteric and venous phases (P = .18). CONCLUSION: At multi-detector row CT, peak mural enhancement of the normal small bowel occurs on average about 50 seconds after intravenous administration of contrast material or 14 seconds after peak aortic enhancement.

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BACKGROUND AND PURPOSE: No controlled, randomized trial has investigated whether intravenous, intra-arterial (IAT), or mechanical thrombolysis is beneficial in children with ischemic stroke. We report 2 children who underwent IAT for acute ischemic stroke and include them in a review about intravenous thrombolysis, IAT, and mechanical thrombolysis for childhood stroke. METHODS: We searched in MEDLINE and EMBASE for studies that reported on treatment of childhood stroke with intravenous thrombolysis, IAT, or mechanical thrombolysis in the presence of occlusion of the basilar artery, sphenoidal, or insular middle cerebral artery. To be included in this review, the following findings had to be reported: (1) stroke severity at presentation; (2) cerebral imaging findings before thrombolysis; (3) time to treatment; (4) dose of the thrombolytic agent; (5) pre- and postinterventional angiographic findings in IAT; and (6) outcome assessed at hospital discharge or within 12 months after thrombolysis. RESULTS: Adequate data were available in 17 children (including our 2 own cases) who underwent intravenous thrombolysis (n=6), IAT (n=10), or mechanical thrombolysis (n=1). No symptomatic intracranial hemorrhage occurred, but 2 asymptomatic intracranial hemorrhages were present. Sixteen children (94%) survived, and 12 (71%) had a good outcome (modified Rankin Scale score 0 or 1). CONCLUSIONS: The available data about thrombolysis in pediatric stroke are limited. They suggest that this treatment may be beneficial in children with ischemic stroke. Controlled, randomized trials are needed to determine whether thrombolysis is useful in childhood stroke.