Cross-correlation image analysis for real-time single particle tracking.

Accurately measuring the translations of objects between images is essential in many fields, including biology, medicine, chemistry, and physics. One important application is tracking one or more particles by measuring their apparent displacements in a series of images. Popular methods, such as the center of mass, often require idealized scenarios to reach the shot noise limit of particle tracking and, therefore, are not generally applicable to multiple image types. More general methods, such as maximum likelihood estimation, reliably approach the shot noise limit, but are too computationally intense for use in real-time applications. These limitations are significant, as real-time, shot-noise-limited particle tracking is of paramount importance for feedback control systems. To fill this gap, we introduce a new cross-correlation-based algorithm that approaches shot-noise-limited displacement detection and a graphics processing unit-based implementation for real-time image analysis of a single particle.

Childhood adversities and risk of posttraumatic stress disorder and major depression following a motor vehicle collision in adulthood.

AIMS: Childhood adversities (CAs) predict heightened risks of posttraumatic stress disorder (PTSD) and major depressive episode (MDE) among people exposed to adult traumatic events. Identifying which CAs put individuals at greatest risk for these adverse posttraumatic neuropsychiatric sequelae (APNS) is important for targeting prevention interventions. METHODS: Data came from n = 999 patients ages 18-75 presenting to 29 U.S. emergency departments after a motor vehicle collision (MVC) and followed for 3 months, the amount of time traditionally used to define chronic PTSD, in the Advancing Understanding of Recovery After Trauma (AURORA) study. Six CA types were self-reported at baseline: physical abuse, sexual abuse, emotional abuse, physical neglect, emotional neglect and bullying. Both dichotomous measures of ever experiencing each CA type and numeric measures of exposure frequency were included in the analysis. Risk ratios (RRs) of these CA measures as well as complex interactions among these measures were examined as predictors of APNS 3 months post-MVC. APNS was defined as meeting self-reported criteria for either PTSD based on the PTSD Checklist for DSM-5 and/or MDE based on the PROMIS Depression Short-Form 8b. We controlled for pre-MVC lifetime histories of PTSD and MDE. We also examined mediating effects through peritraumatic symptoms assessed in the emergency department and PTSD and MDE assessed in 2-week and 8-week follow-up surveys. Analyses were carried out with robust Poisson regression models. RESULTS: Most participants (90.9%) reported at least rarely having experienced some CA. Ever experiencing each CA other than emotional neglect was univariably associated with 3-month APNS (RRs = 1.31-1.60). Each CA frequency was also univariably associated with 3-month APNS (RRs = 1.65-2.45). In multivariable models, joint associations of CAs with 3-month APNS were additive, with frequency of emotional abuse (RR = 2.03; 95% CI = 1.43-2.87) and bullying (RR = 1.44; 95% CI = 0.99-2.10) being the strongest predictors. Control variable analyses found that these associations were largely explained by pre-MVC histories of PTSD and MDE. CONCLUSIONS: Although individuals who experience frequent emotional abuse and bullying in childhood have a heightened risk of experiencing APNS after an adult MVC, these associations are largely mediated by prior histories of PTSD and MDE.

Prior differences in previous trauma exposure primarily drive the observed racial/ethnic differences in posttrauma depression and anxiety following a recent trauma.

BACKGROUND: Racial and ethnic groups in the USA differ in the prevalence of posttraumatic stress disorder (PTSD). Recent research however has not observed consistent racial/ethnic differences in posttraumatic stress in the early aftermath of trauma, suggesting that such differences in chronic PTSD rates may be related to differences in recovery over time. METHODS: As part of the multisite, longitudinal AURORA study, we investigated racial/ethnic differences in PTSD and related outcomes within 3 months after trauma. Participants (n = 930) were recruited from emergency departments across the USA and provided periodic (2 weeks, 8 weeks, and 3 months after trauma) self-report assessments of PTSD, depression, dissociation, anxiety, and resilience. Linear models were completed to investigate racial/ethnic differences in posttraumatic dysfunction with subsequent follow-up models assessing potential effects of prior life stressors. RESULTS: Racial/ethnic groups did not differ in symptoms over time; however, Black participants showed reduced posttraumatic depression and anxiety symptoms overall compared to Hispanic participants and White participants. Racial/ethnic differences were not attenuated after accounting for differences in sociodemographic factors. However, racial/ethnic differences in depression and anxiety were no longer significant after accounting for greater prior trauma exposure and childhood emotional abuse in White participants. CONCLUSIONS: The present findings suggest prior differences in previous trauma exposure partially mediate the observed racial/ethnic differences in posttraumatic depression and anxiety symptoms following a recent trauma. Our findings further demonstrate that racial/ethnic groups show similar rates of symptom recovery over time. Future work utilizing longer time-scale data is needed to elucidate potential racial/ethnic differences in long-term symptom trajectories.

Spin-orbit-driven band inversion in bilayer graphene by the van der Waals proximity effect.

Spin-orbit coupling (SOC) is the key to realizing time-reversal-invariant topological phases of matter1,2. SOC was predicted by Kane and Mele3 to stabilize a quantum spin Hall insulator; however, the weak intrinsic SOC in monolayer graphene4-7 has precluded experimental observation in this material. Here we exploit a layer-selective proximity effect-achieved via a van der Waals contact with a semiconducting transition-metal dichalcogenide8-21-to engineer Kane-Mele SOC in ultra clean bilayer graphene. Using high-resolution capacitance measurements to probe the bulk electronic compressibility, we find that SOC leads to the formation of a distinct, incompressible, gapped phase at charge neutrality. The experimental data agree quantitatively with a simple theoretical model in which the new phase results from SOC-driven band inversion. In contrast to Kane-Mele SOC in monolayer graphene, the inverted phase is not expected to be a time-reversal-invariant topological insulator, despite being separated from conventional band insulators by electric-field-tuned phase transitions where crystal symmetry mandates that the bulk gap must close22. Our electrical transport measurements reveal that the inverted phase has a conductivity of approximately e2/h (where e is the electron charge and h Planck's constant), which is suppressed by exceptionally small in-plane magnetic fields. The high conductivity and anomalous magnetoresistance are consistent with theoretical models that predict helical edge states within the inverted phase that are protected from backscattering by an emergent spin symmetry that remains robust even for large Rashba SOC. Our results pave the way for proximity engineering of strong topological insulators as well as correlated quantum phases in the strong spin-orbit regime in graphene heterostructures.

MRI-guided, open trial of abciximab for ischemic stroke within a 3- to 24-hour window.

The authors assessed the effect of IV abciximab on early neurologic improvement and ischemic lesion growth in 29 patients with supratentorial stroke and NIH stroke scale score (NIHSSS) > or = 4 (11.1 +/- 5.9), treated within 3 to 24 (13.6 +/- 5.5) hours of onset. The 48 to 72-hour NIHSSS improvement was 4.4 +/- 3.2 and the 24-hour lesion growth on DWI was +23% (-50%, +103%); 7/26 (27%) patients experienced lesion size decrease. Treatment of sub-24-hour stroke with abciximab improves early post-treatment neurologic status and often attenuates ischemic lesion growth.

Lack of clinical significance of early ischemic changes on computed tomography in acute stroke.

CONTEXT: The prevalence and clinical significance of early ischemic changes (EICs) on baseline computed tomography (CT) scan of the head obtained within 3 hours of ischemic stroke are not established. OBJECTIVE: To determine the frequency and significance of EIC on baseline head CT scans in the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA (recombinant tissue plasminogen activator) Stroke Trial. DESIGN AND SETTING: The original study, a randomized controlled trial, took place from January 1991 through October 1994 at 43 sites, during which CT images were obtained within 3 hours of symptom onset and prior to the initiation of rt-PA or placebo. For the current analysis, detailed reevaluation was undertaken after October 1994 of all baseline head CT scans with clinical data available pretreatment (blinded to treatment arm). PATIENTS: Of 624 patients enrolled in the trial, baseline CT scans were retrieved and reviewed for 616 (99%). MAIN OUTCOME MEASURES: Frequency of EICs on baseline CT scans; association of EIC with other baseline variables; effect of EICs on deterioration at 24 hours (>/=4 points increase from the baseline National Institutes of Health Stroke Scale [NIHSS] score); clinical outcome (measured by 4 clinical scales) at 3 months, CT lesion volume at 3 months, death at 90 days; and symptomatic intracranial hemorrhage (ICH) within 36 hours of treatment. RESULTS: The prevalence of EIC on baseline CT in the combined rt-PA and placebo groups was 31% (n = 194). The EIC was significantly associated with baseline NIHSS score (rho = 0.23; P<.001) and time from stroke onset to baseline CT scan (rho = 0.11; P =.007). After adjusting for baseline variables, there was no EIC x treatment interaction detected for any clinical outcome, including deterioration at 24 hours, 4 clinical scales, lesion volume, and death at 90 days (P>/=.25), implying that EIC is unlikely to affect response to rt-PA treatment. After adjusting for NIHSS score (an independent predictor of ICH), no EIC association with symptomatic ICH at 36 hours was detected in the group treated with rt-PA (P>/=.22). CONCLUSIONS: Our analysis suggests that EICs are prevalent within 3 hours of stroke onset and correlate with stroke severity. However, EICs are not independently associated with increased risk of adverse outcome after rt-PA treatment. Patients treated with rt-PA did better whether or not they had EICs, suggesting that EICs on CT scan are not critical to the decision to treat otherwise eligible patients with rt-PA within 3 hours of stroke onset.

Outcome of stroke patients without angiographically revealed arterial occlusion within four hours of symptom onset.

BACKGROUND AND PURPOSE: Follow-up imaging data from stroke patients without angiographically apparent arterial occlusions at symptom onset are lacking. We reviewed our Emergency Management of Stroke (EMS) trial experience to determine the clinical and imaging outcomes of patients with ischemic stroke who showed no arterial occlusion on angiograms obtained within 4 hours of symptom onset. METHODS: All patients in this report were participants in the EMS trial that was designed to address the safety and potential efficacy of combined IV and intraarterial thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) in patients with acute ischemic stroke. RESULTS: Thirty-five patients were randomized to receive either IV rt-PA (n = 17) or placebo (n = 18), followed by cerebral angiography. No symptomatic arterial occlusion was evident in 10 (29%) of the 34 patients. Eight (80%) of 10 patients without angiographically apparent clot within 4 hours of symptom onset had a new cerebral infarction confirmed on follow-up brain imaging. The median 72-hour infarction volume was 2.4 cc (range, 1-30 cc). Four of the 10 "no-clot" patients had a favorable 3-month outcome as assessed by Barthel Index (score, 95 or 100) and modified Rankin Scale (score, 0 or 1). The six remaining patients had 3-month Rankin Scale scores of 1 (Barthel of 90), 2, 3, 4, or 5. CONCLUSION: Acute ischemic stroke patients with a neurologic deficit but a negative angiogram during the first 4 hours after symptom onset usually develop image-documented cerebral infarction, and approximately half suffer from long-term functional disability. The two most likely explanations for negative angiograms are very early irreversible ischemic damage despite recanalization or ongoing ischemia secondary to clot in non-visible penetrating arterioles or in the microvasculature.

Treatment of acute ischemic stroke.

Acute ischemic stroke is the third leading cause of death in the United States and the leading cause of adult disability. The direct and indirect costs of stroke care exceed $51 billion annually. In 1996, the US Food and Drug Administration approved the first treatment for acute ischemic stroke, intravenous tissue plasminogen activator. Later that year, the National Institute of Neurologic Disorders and Stroke (a branch of the National Institutes of Health) convened a consensus conference on the Rapid Identification and Treatment of Acute Ischemic Stroke, setting goals for stroke care in the United States. Since then, it has become imperative that emergency physicians understand the pathophysiology of stroke, the basis and rationale for treatment, and the therapeutic approaches. This article reviews the state of the art of acute stroke treatment, its foundation, as well as its future.

Recombinant chemosensory protein (CSP2) from the moth Mamestra brassicae: crystallization and preliminary crystallographic study.

Chemosensory proteins (CSPs) are small proteins (13 kDa on average) present in several sensory organs from a wide range of insect species. They are believed to be involved in chemoperception (olfaction or taste) and to play a role in chemical transport from air or water to chemosensitive receptors. Here, the first crystals of a CSP originating from the moth Mamestra brassicae (Mbra) proboscis and expressed as recombinant protein in Escherichia coli periplasm are reported. Crystals of MbraCSP2 were obtained by the hanging-drop vapour-diffusion method under the following conditions: 1 microl of a 46 mg ml(-1) protein solution in 50 mM Tris pH 8.0 containing cetyl alcohol as ligand (1:5 molar ratio) was mixed with 1 microl of well solution containing 30% PEG 4000, 0.2 M sodium acetate in 100 mM Tris at pH 8.4. The protein-cetyl alcohol complex crystallizes in space group P2(1), with unit-cell parameters a = 47.9, b = 49.7, c = 50.3 A, beta = 110.1 degrees. With two molecules in the asymmetric unit, the V(M) is 2.15 A(3) Da(-1) and the solvent content is 42%. A complete data set has been collected at 1.6 A resolution on beamline ID14-2 (ESRF, Grenoble). Se-Met expression has been performed with a view to solving the CSP2 structure with MAD data collection using the Se absorption edge.

Early stroke treatment associated with better outcome: the NINDS rt-PA stroke study.

BACKGROUND: The National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study showed a similar percentage of intracranial hemorrhage and good outcome in patients 3 months after stroke treatment given 0 to 90 minutes and 91 to 180 minutes after stroke onset. At 24 hours after stroke onset more patients treated 0 to 90 compared to 91 to 180 minutes after stroke onset had improved by four or more points on the NIH Stroke Scale (NIHSS). The authors performed further analyses to characterize the relationship of onset-to-treatment time (OTT) to outcome at 3 months, early improvement at 24 hours, and intracranial hemorrhage within 36 hours. METHODS: Univariate analyses identified potentially confounding variables associated with OTT that could mask an OTT-treatment interaction. Tests for OTT-treatment interactions adjusting for potential masking confounders were performed. An OTT-treatment interaction was considered significant if p < or = 0.10, implying that treatment effectiveness was related to OTT. RESULTS: For 24-hour improvement, there were no masking confounders identified and there was an OTT-treatment interaction (p = 0.08). For 3-month favorable outcome, the NIHSS met criteria for a masking confounder. After adjusting for NIHSS as a covariate, an OTT-treatment interaction was detected (p = 0.09): the adjusted OR (95% CI) for a favorable 3-month outcome associated with recombinant tissue-type plasminogen activator (rt-PA) was 2.11 (1.33 to 3.35) in the 0 to 90 minute stratum and 1.69 (1.09 to 2.62) in the 91 to 180 minute stratum. In the group treated with rt-PA, after adjusting for baseline NIHSS, an effect of OTT on the occurrence of intracranial hemorrhage was not detected. CONCLUSIONS: If the NINDS rt-PA Stroke Trial treatment protocol is followed, this analysis suggests that patients treated 0 to 90 minutes from stroke onset with rt-PA have an increased odds of improvement at 24 hours and favorable 3-month outcome compared to patients treated later than 90 minutes. No effect of OTT on intracranial hemorrhage was detected within the group treated with rt-PA, possibly due to low power.

Tissue plasminogen activator for acute ischemic stroke in patients with unruptured cerebral aneurysms.

Intracranial hemorrhage (ICH) is the most feared complication of thrombolytic therapy for acute ischemic stroke. There are limited data on the risks of thrombolysis in patients with asymptomatic intracranial aneurysm. We report 2 adults with signs of hemispheric ischemia who were successfully treated with intravenous tissue plasminogen activator (t-PA), despite the presence of asymptomatic intracranial aneurysm. The presence of an asymptomatic intracranial aneurysm may not necessarily preclude a good outcome from acute ischemic stroke treated with rt-PA. Selected patients harboring incidental, unruptured intracranial aneurysm may benefit from thrombolytics.

Combined intravenous and intra-arterial r-TPA versus intra-arterial therapy of acute ischemic stroke: Emergency Management of Stroke (EMS) Bridging Trial.

BACKGROUND AND PURPOSE: The purpose of this study was to test the feasibility, efficacy, and safety of combined intravenous (IV) and local intra-arterial (IA) recombinant tissue plasminogen activator (r-TPA) therapy for stroke within 3 hours of onset of symptoms. METHODS: This was a double-blind, randomized, placebo-controlled multi-center Phase I study of IV r-TPA or IV placebo followed by immediate cerebral arteriography and local IA administration of r-TPA by means of a microcatheter. Treatment activity was assessed by improvement on the National Institutes of Health Stroke Scale Score (NIHSSS) at 7 to 10 days. The Barthel Index, modified Rankin Scale, and the Glasgow Outcome Scale measured 3-month functional outcome. Arterial recanalization rates and their relation to total r-TPA dose and time to lysis were measured. Rates of life-threatening bleeding, intracerebral hemorrhage (ICH), or other bleeding complications assessed safety. RESULTS: Thirty-five patients were randomly assigned, 17 into the IV/IA group and 18 into the placebo/IA group. There was no difference in the 7- to 10-day or the 3-month outcomes, although there were more deaths in the IV/IA group. Clot was found in 22 of 34 patients. Recanalization was better (P=0. 03) in the IV/IA group with TIMI 3 flow in 6 of 11 IV/IA patients versus 1 of 10 placebo/IA patients and correlated to the total dose of r-TPA (P=0.05). There was no difference in the median treatment intervals from time of onset to IV treatment (2.6 vs 2.7 hours), arteriography (3.3 vs 3.0 hours), or clot lysis (6.3 vs 5.7 hours) between the IV/IA and placebo/IA groups, respectively. A direct relation between NIHSSS and the likelihood of the presence of a clot was identified. Eight ICHs occurred; all were hemorrhagic infarctions. There were no parenchymal hematomas. Symptomatic ICH within 24 hours occurred in 1 placebo/IA patient only. Beyond 24 hours, symptomatic ICH occurred in 2 IV/IA patients only. Life-threatening bleeding complications occurred in 2 patients, both in the IV/IA group. Moderate to severe bleeding complications occurred in 2 IV/IA patients and 1 placebo/IA patient. CONCLUSIONS: This pilot study demonstrates combined IV/IA treatment is feasible and provides better recanalization, although it was not associated with improved clinical outcomes. The presence of thrombus on initial arteriography was directly related to the baseline NIHSSS. This approach is technically feasible. The numbers of symptomatic ICH were similar between the 2 groups, which suggests that this approach may be safe. Further study is needed to determine the safety and effectiveness of this new method of treatment. Such studies should address not only efficacy and safety but also the cost-benefit ratio and quality of life, given the major investment in time, personnel, and equipment required by combined IV and IA techniques.

Tobacco mosaic virus inoculation inhibits wound-induced jasmonic acid-mediated responses within but not between plants.

Jasmonic acid (JA) and salicylic acid (SA) have both been implicated as important signal molecules mediating induced defenses of Nicotiana tabacum L. against herbivores and pathogens. Since the application of SA to a wound site can inhibit both wound-induced JA and a defense response that it elicits, namely nicotine production, we determined if tobacco mosaic virus (TMV) inoculation, with its associated endogenous systemic increase in SA, reduces a plant's ability to increase JA and nicotine levels in response to mechanical damage, and evaluated the consequences of these interactions for the amount of tissue removed by a nicotine-tolerant herbivore, Manduca sexta. Additionally, we determined whether the release of volatile methyl salicylic acid (MeSA) from inoculated plants can reduce wound-induced JA and nicotine responses in uninoculated plants sharing the same chamber. The TMV-inoculated plants, though capable of inducing nicotine normally in response to methyl jasmonate applications, had attenuated wound-induced JA and nicotine responses. Moreover, larvae consumed 1.7- to 2.7-times more leaf tissue from TMV-inoculated plants than from mock-inoculated plants. Uninoculated plants growing in chambers downwind of either TMV-inoculated plants or vials releasing MeSA at 83- to 643-times the amount TMV-inoculated plants release, exhibited normal wound-induced responses. We conclude that tobacco plants, when inoculated with TMV, are unable to elicit normal wound responses, due likely to the inhibition of JA production by the systemic increase in SA induced by virus-inoculation. The release of volatile MeSA from inoculated plants is not sufficient to influence the wound-induced responses of neighboring plants.

Agreement and variability in the interpretation of early CT changes in stroke patients qualifying for intravenous rtPA therapy.

BACKGROUND AND PURPOSE: Ischemic changes identified on CT scans performed in the first few hours after stroke onset, which are thought to possibly represent early cytotoxic edema and development of irreversible injury, may have important implications for subsequent treatment. However, insecurity and conflicting data exist over the ability of clinicians to correctly recognize and interpret these changes. We performed a detailed review of selected baseline CT scans from the NINDS rt-PA Stroke Trial to test agreement among experienced stroke specialists and other physicians on the presence of early CT ischemic changes. METHODS: Seventy baseline CT scans from the NINDS Stroke Trial were read and classified for the presence or absence of various early findings of ischemia by 16 individuals, including NINDS trial investigators, other neurologists, other emergency medicine physicians, and radiology or stroke fellows. CT scans included normal scans and scans from patients who later developed symptomatic intracranial hemorrhage, as well as scans on which the NINDS rt-PA Stroke Trial neuroradiologist identified clear-cut early CT changes. For each CT finding, kappa-statistics were used to assess the proportion of agreement beyond chance. RESULTS: kappa-Values (95% confidence interval [CI]) ranged from 0.20 (-0.20, 0.61) (fair agreement) to 0.41 (0.37, 0.45) (moderate agreement) among the 16 viewers, and the kappa-value was only 0.39 (0.29, 0.49) (fair) in answer to the question "do early CT changes involve more than one third of the MCA [middle cerebral artery] territory?" There was substantial variability within each specialty group and between groups. kappa-Values were only fair to moderate even among physicians experienced in selecting and treating acute stroke patients with rtPA. Observed agreement ranged from 68% to 85%. Physicians agreed on the finding of early CT changes involving >33% of the MCA territory 77% of the time, although the kappa-value of 0.39 suggested only moderate agreement beyond chance. CONCLUSIONS: There is considerable lack of agreement, even among experienced clinicians, in recognizing and quantifying early CT changes. Improved methods of recognizing and quantifying early ischemic brain damage are needed.

Effects of tissue plasminogen activator for acute ischemic stroke at one year. National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator Stroke Study Group.

BACKGROUND: In 1995, the two-part National Institute of Neurological Disorders and Stroke (NINDS) Recombinant Tissue Plasminogen Activator Stroke Trial found that patients who were treated with tissue plasminogen activator (t-PA) within three hours after the onset of symptoms of acute ischemic stroke were at least 30 percent more likely than patients given placebo to have minimal or no disability three months after the stroke. It was unknown, however, whether the benefit would be sustained for longer periods. METHODS: In the NINDS Trial, a total of 624 patients with stroke were randomly assigned to receive either t-PA or placebo. We collected outcome data over a period of 12 months after the occurrence of stroke. The primary outcome measure was a "favorable outcome," defined as minimal or no disability as measured by the Barthel index, the modified Rankin Scale, and the Glasgow Outcome Scale. We assessed the treatment effect using a global statistic. RESULTS: Using an intention-to-treat analysis for the combined results of the two parts of the trial at 6 months and 12 months, we found that the global statistic favored the t-PA group (odds ratio for a favorable outcome at 6 months, 1.7; 95 percent confidence interval, 1.3 to 2.3; odds ratio at 12 months, 95 percent confidence interval, 1.7; 1.2 to 2.3). The patients treated with t-PA were at least 30 percent more likely to have minimal or no disability at 12 months than were the placebo-treated patients (absolute increase in the proportion with a favorable outcome, 11 to 13 percentage points). There was no significant difference in mortality at 12 months between the t-PA group and the placebo group (24 percent vs. 28 percent, P=0.29). There was no interaction between the type of stroke identified at base line and treatment with respect to the long-term response. The rate of recurrent stroke at 12 months was similar in the two groups. CONCLUSIONS: During 12 months of follow-up, the patients with acute ischemic stroke who were treated with t-PA within three hours after the onset of symptoms were more likely to have minimal or no disability, than the patients given placebo. These results indicate a sustained benefit of t-PA for such patients.

A molecular study of euglenoid phylogeny using small subunit rDNA.

The euglenoids are an ancient and extremely diverse lineage of eukaryotic flagellates with unclear relationships among taxa. Synapomorphies for the euglenoids include a surface pellicle and a closed mitosis with a series of separate sub-spindles. The taxonomy currently in use is inconsistent with the available data and needs revision. Most euglenoid phylogenies are largely intuitive reconstructions based on a limited number of morphological characters. Therefore, we have added molecular characters from the Small Subunit (SSU) rDNA to generate an overall phylogenetic framework for the euglenoids. SSU rDNA sequences from photosynthetic, osmotrophic, and phagotrophic euglenoids were aligned based on secondary structure. Phylogenetic analysis using the conserved areas of the sequence was performed using parsimony, maximum likelihood, and distance methods. Trees derived using different criteria are in agreement. The euglenoids form a distinct monophyletic clade with phagotrophic members diverging prior to the phototrophic and osmotrophic members. Among photosynthetic members, the biflagellate form diverged prior to the uniflagellate form. Additionally, the genus Euglena appears to be paraphyletic, with osmotrophic taxa, such as Astasia and Khawkinea, diverging independently within the clade containing the photosynthetic genus Euglena.

Hypertension and its treatment in the NINDS rt-PA Stroke Trial.

BACKGROUND AND PURPOSE: We examined the frequency, course, and treatment of hypertension in the NINDS rt-PA Stroke Trial. METHODS: Blood pressure (BP) was measured at the time of admission, at randomization, and then 36 times during the first 24 hours after randomization. Patients with a systolic BP of >185 mm Hg and a diastolic BP of >110 mm Hg at admission were defined as hypertensive before randomization, and those with a systolic BP of >180 mm Hg or a diastolic BP of >105 mm Hg within the first 24 hours after randomization were defined as hypertensive after randomization. Standardized clinical assessments were conducted at 24 hours and at 3 months. Post hoc analyses were conducted to evaluate the association of antihypertensive therapy with clinical outcomes. RESULTS: Of the 624 patients, 121(19%) had hypertension on admission and 372 (60%) had hypertension in the 24 hours after randomization. The use of antihypertensive therapy before randomization (tPA 9%, placebo 9%) and after randomization (tPA 24%, placebo 29%) was similar between placebo- and tPA-treated patients. No adverse effects of prerandomization antihypertensive therapy on 3-month favorable outcome were detected for either the placebo- or tPA-treated groups. For placebo patients with hypertension in the 24 hours after randomization, clinical outcome measures were similar for those patients who did and did not receive antihypertensive therapy after randomization (P > or = 0.26); antihypertensive therapy was not associated with declines in BP (P = 0.44) or with abrupt declines (P = 0.14). Those tPA patients who were hypertensive after randomization and received antihypertensive therapy were less likely to have a favorable outcome at 3 months (P < 0.01) than those who were hypertensive and did not receive antihypertensive therapy. CONCLUSIONS: The frequency of hypertension and the use of antihypertensive therapy were similar between the tPA and placebo groups in the NINDS rt-PA Stroke Trial. In the placebo group, antihypertensive therapy was not associated with less favorable outcomes at 3 months; postrandomization antihypertensive therapy was associated with less favorable outcomes for the tPA patients who were hypertensive. However, because of the nonrandomized use of antihypertensive therapy and the many post hoc comparisons leading to type 1 errors, the significance of this observation is unclear. Careful attention to BP and gentle management remain warranted for stroke patients treated with tPA.