Manipulation Of Pressure Research Articles

Precise control of end‐tidal carbon dioxide and oxygen improves BOLD and ASL cerebrovascular reactivity measures

In-depth investigation of cerebrovascular blood flow and MR mechanisms underlying the blood oxygenation level dependent signal requires precise manipulation of the arterial partial pressure of carbon dioxide and oxygen, measured by their noninvasive surrogates, the end-tidal values. The traditional methodology consists of administering a fixed fractional concentration of inspired CO(2), but this causes a variable ventilatory response across subjects, resulting in different values of end-tidal partial pressures of CO(2) and O(2). In this study, we investigated whether fine control of these end-tidal partial pressures would improve stability and predictability of blood oxygenation level dependent and arterial spin labeling signals for studying cerebrovascular reactivity. In 11 healthy volunteers, we compared the MR signals generated by the traditional fixed fractional concentration of inspired CO(2) method to those of an automated feed-forward system, a simpler, safer, and more compact alternative to dynamic end-tidal forcing systems, designed to target constant end-tidal partial pressures of CO(2) and O(2). We found that near square-wave changes in end-tidal partial pressure of CO(2) of 5, 7.5, and 10 mm Hg (+/-1.01 mm Hg within two to three breaths) and constrained changes in the end-tidal partial pressure of O(2) (<10 mm Hg) induced cerebral vascular reactivity measurements with faster transitions, together with improved stability and gradation, than those achieved with the traditional fixed fractional concentration of inspired CO(2) method.

Dielectrophoretic cell trapping and parallel one-to-one fusion based on field constriction created by a micro-orifice array

Micro-orifice based cell fusion assures high-yield fusion without compromising the cell viability. This paper examines feasibility of a dielectrophoresis (DEP) assisted cell trapping method for parallel fusion with a micro-orifice array. The goal is to create viable fusants for studying postfusion cell behavior. We fabricated a microfluidic chip that contained a chamber and partition. The partition divided the chamber into two compartments and it had a number of embedded micro-orifices. The voltage applied to the electrodes located at each compartment generated an electric field distribution concentrating in micro-orifices. Cells introduced into each compartment moved toward the micro-orifice array by manipulation of hydrostatic pressure. DEP assisted trapping was used to keep the cells in micro-orifice and to establish cell to cell contact through orifice. By applying a pulse, cell fusion was initiated to form a neck between cells. The neck passing through the orifice resulted in immobilization of the fused cell pair at micro-orifice. After washing away the unfused cells, the chip was loaded to a microscope with stage top incubator for time lapse imaging of the selected fusants. The viable fusants were successfully generated by fusion of mouse fibroblast cells (L929). Time lapse observation of the fusants showed that fused cell pairs escaping from micro-orifice became one tetraploid cell. The generated tetraploid cells divided into three daughter cells. The fusants generated with a smaller micro-orifice (diameter approximately 2 mum) were kept immobilized at micro-orifice until cell division phase. After observation of two synchronized cell divisions, the fusant divided into four daughter cells. We conclude that the presented method of cell pairing and fusion is suitable for high-yield generation of viable fusants and furthermore, subsequent study of postfusion phenomena.

Feasibility of In Vivo Pressure Measurement Using a Pressure-Tip Catheter via Transventricular Puncture

Pressure-tip catheters (PTCs) are used to evaluate ventricular mechanics during surgical repair of congenital heart disease in children. Studies in infants require miniaturized sensors. We compared the safety and accuracy of a 2-Fr ultraminiature PTC with a 5-Fr PTC. In 10 piglets (weight 19-22 kg), a 5-Fr PTC was inserted through a 3-mm apical puncture with a #11 blade. A 20-gauge angiocatheter was inserted using a separate site. A 2-Fr PTC was threaded through the angiocatheter lumen. The angiocatheter was withdrawn, leaving the 2-Fr PTC within the left ventricle (LV). Left ventricular pressure (LVP) changes were measured during three inferior vena caval occlusions. Reliability coefficients demonstrated correlation between the 2-Fr PTC and 5-Fr PTC for LV end-diastolic pressure (0.90-0.95), peak LVP (0.92-0.99), and the maximal (0.87-0.93) and minimal (0.89-0.94) first derivatives of LVP. Bland-Altman analysis demonstrated agreement for all variables. Blood loss was trivial with pressure manipulation and catheter placement and removal. Pressure measurements using the 2-Fr PTC were accurate and comparable with those from the 5-Fr PTC. Transventricular placement of a 2-Fr PTC is feasible and should allow evaluation of ventricular mechanics during surgical repair of congenital heart disease.

Feasible Input Manipulation for a Nonisothermal Direct Methanol Fuel Cell System

Through a semiexperimental dynamic modeling of a direct methanol fuel cell (DMFC) system, transient behaviors on describing cell temperature, methanol crossover, water crossover, and electric power are presented. By different operating manners, the new input determinations are addressed. To investigate the performance of DMFC systems, the presented fuel and exergetic efficiencies for the specific probe of energy utilization are evaluated. Through both steady-state and unsteady state analyses, the manipulation of cathode pressure and anode inlet flow temperature is a feasible approach for temperature regulation, but methanol crossover is restricted.

Baroreflex control of heart rate in the broad-nosed caiman Caiman latirostris is temperature dependent

It has been suggested that ectothermic vertebrates primarily control blood pressure to protect the pulmonary vasculature from oedema caused by high pressure, while endothermic vertebrates control blood pressure to maintain adequate oxygen delivery to the tissues. In the present study we have characterised how temperature affects the cardiac limb of the baroreflex in the intact unanaesthetized broad-nosed caiman (Caiman latirostris) by pharmacological manipulation of blood pressure in a “closed-loop” system. Sodium nitroprusside (SNP) and phenylephrine were used to manipulate arterial pressure and the resulting alterations in heart rate were used to calculate the gain of the baroreflex. Both drugs were infused as bolus injections in concentrations of 5, 10, 25, 50 and 100µgkg−1. The barostatic response was present at both 15 and 30°C, and, at both temperatures, C. latirostris responded to reductions in systemic blood pressure (Psys). At 30°C the baroreflex was more pronounced at a blood pressure lower than control value (52.3cmH2O) with a maximal baroreflex gain of 1.97beatsmin−1cmH2O−1 at a Psys of 41.9cmH2O, and therefore seems to counteract hypotension. In contrast, the maximal baroreflex at 15°C was found at a Psys almost equal to the control value. The highest baroreflex gain in response to change in blood pressure was measured at the highest temperature. Thus, C. latirostris exhibit a temperature dependent barostatic response.

Laser‐speckle analysis of renal cortical perfusion – regional perfusion dynamics

Tubuloglomerular feedback and a myogenic mechanism act on afferent arterioles to mediate autoregulation of renal blood flow (RBF) and their actions may extend beyond single nephrons. We tested for physiologically significant coupling among neighboring nephrons. Cortical surface perfusion was assessed by laser‐speckle perfusion imaging at 1 Hz. Time series from 5 regions of interest (ROI, ~0.5 × 0.5 mm) were extracted. RBF (Transonic 400) was systematically altered by manipulation of perfusion pressure, by captopril (−/+ ANG II), and by L‐NAME. Perfusion in the ROIs (units) was linear in RBF (slope = 1120 ± 63 units × min/mL, r2 = 0.94 ± 0.03, n=5). Power spectra of the ROI time series contain the same information as RBF spectra and spectra of all ROIs are very similar. Comparing adjacent to remotely located ROIs by spectra of difference series, by linear cross spectra, and by nonlinear cross bi‐spectra showed that coupling decreased with separation between ROIs. The cross bi‐spectral coupling index declined with separation of ROIs: adjacent = 0.269, medium = 0.170, remote = 0 during control (greater index = greater coupling). ANG II infusion increased the spread of coupling: adjacent = 0.133, medium = 0.034, remote = 0.014. Local coupling suggests that autoregulation may involve coordinate action of clusters of nephrons. Coupling may be regulated by ANG II.Funded by Heart &amp; Stroke Fdn of BC &amp; Yukon, &amp; Victoria Fdn

Psychological, muscular and kinematic factors mediate performance under pressure

It is well established that performance is influenced by pressure, but the underlying mechanisms of the pressure-performance relationship are poorly understood. To address this important issue, the current experiment evaluated psychological, physiological, and kinematic factors as mediators of the pressure-performance relationship. Psychological, physiological, and kinematic responses to three levels of competitive pressure were measured in 23 males and 35 females during a golf putting task. Pressure manipulations impaired putting performance. Self-reported anxiety, effort, and perceived pressure were increased. Heart rate, heart rate variability, muscle activity, and lateral clubhead acceleration were also elevated. Mediation analyses revealed that effort, muscle activity, and lateral acceleration partially mediated the decline in performance. Results confirmed that pressure elicits effects on performance through multiple pathways.

Introduction to High‐Pressure Bioscience and Biotechnology

The manipulation of biological materials using elevated pressure is providing an ever-growing number of opportunities in both the applied and basic sciences. Manipulation of pressure is a useful parameter for enhancing food quality and shelf life; inactivating microbes, viruses, prions, and deleterious enzymes; affecting recombinant protein production; controlling DNA hybridization; and improving vaccine preparation. In biophysics and biochemistry, pressure is used as a tool to study intermediates in protein folding, enzyme kinetics, macromolecular interactions, amyloid fibrous protein aggregation, lipid structural changes, and to discern the role of solvation and void volumes in these processes. Biologists, including many microbiologists, examine the utility and basis of pressure inactivation of cells and cellular processes, and conversely seek to discover how deep-sea life has evolved a preference for high-pressure environments. This introduction and the papers that follow provide information on the nature and promise of the highly interdisciplinary field of high-pressure bioscience and biotechnology (HPBB).

The surprisingly low motivational power of future rewards: Comparing conventional money-based measures of discounting with motivation-based measures

Temporal discount rates are often poor predictors of behaviors that we expect will be motivated by the future. The current research suggests this may be because conventional discounting measures are poor measures of the motivational value of future rewards. In six studies, I develop motivation-based measures of the present value (PV) of future rewards and compare the PVs obtained with those obtained using conventional money-based discounting measures. Conventional money-based PVs consistently overestimate motivation-based PVs and are discriminable from them. I explore explanations for this mismatch, including timing of effort exertion (Study 2) and loss aversion (Study 3), both features of the motivation-based measures. In Study 5, I use self-reports of valuation strategies and a time pressure manipulation to demonstrate that participants use different valuation strategies in the conventional money-based and the motivation-based measures that, in part, determine the difference in PVs obtained and the relatively low correspondence between them.

Static Autoregulation is Intact in Majority of Patients With Severe Traumatic Brain Injury

The management of severe traumatic brain injury (sTBI) patients with and without intact cerebral pressure autoregulation (CPA) varies markedly. Recent studies, analyzing beat-to-beat interactions between intracranial pressure (ICP) and systolic blood pressure, or transcranial Doppler velocity changes during a rapid drop in cerebral perfusion pressure (CPP), suggest that CPA is disrupted after sTBI. We use computed tomography perfusion (CTP) to guide blood pressure manipulation in sTBI and have found CPA results that differ with this literature. We present these results here and suggest modifying our basic concepts of CPA disruption. We tested CPA in 24 consecutive sTBI patients using CTP. ICP was monitored intraparenchymally and blood pressure with an arterial line. After a CTP study at baseline, a phenylephrine infusion was used to raise the CPP by 20 mm Hg, and a second CTP was performed immediately thereafter. Quantitative analysis of cerebral blood flow (CBF) was done offline. CPA was considered intact if CBF was unchanged despite the increase in CPP and disrupted if CBF rose after CPP manipulation. CPA was intact in 25 of 33 patients (75.7%) and disrupted in 8 of 33 patients (24.3%). The mean age was significantly different for the 2 groups; 52 years for the disrupted group, 29 years for the intact group (p < 0.0003). The mean ICP change was also statistically different; 3.8 for the disrupted group and 1.5 for the intact group (p < 0.006). Injury Severity Score (ISS), Glasgow Coma Scale, and CPP were not statistically different between the two groups. By using direct measurement of CBF in response to a CPP challenge, we found CPA disruption to be much less common than reported in similar groups of sTBI patients. This difference reflects potentially important separate aspects of CPA. We suggest that CPA measurement using beat-to-beat interactions and transcranial Doppler measurements reflect dynamic CPA processes (dynamic autoregulation), whereas our method reflects steady-state conditions (static autoregulation). If the major disruption of CPA after sTBI involves dynamic vascular responsiveness, perhaps we need more focus on this aspect and less on static-CPP manipulation in terms of pathophysiology and treatment.

Choking vs. Clutch Performance: A Study of Sport Performance under Pressure

Choking research in sport has suggested that an athlete's tendency to choke, versus give a better than usual (i.e., "clutch") performance depends on his or her personality, as well as on situational influences, such as a reliance on explicit (versus implicit) knowledge when pressured. The current study integrated these hypotheses and tested a structural equation model (SEM) to predict sport performance under pressure. Two hundred and one participants attempted two sets of 15 basketball free throws, and were videotaped during their second set of shots as a manipulation of pressure. Results of the model suggest that "reinvesting" attention in the task leads to greater anxiety (cognitive and somatic), which then predicts a higher level of self-focus; self-focus, then, did not lead to improved performance under pressure, whereas feelings of self-reported "perceived control" did help performance. Implications for measurement of these constructs, and their relationships with performance, are discussed.

Brain tissue oxygen monitoring in traumatic brain injury and major trauma: outcome analysis of a brain tissue oxygen–directed therapy

Cerebral ischemia is the leading cause of preventable death in cases of major trauma with severe traumatic brain injury (TBI). Intracranial pressure (ICP) control and cerebral perfusion pressure (CPP) manipulation have significantly reduced the mortality but not the morbidity rate in these patients. In this study, the authors describe their 5-year experience with brain tissue oxygen (PbtO(2)) monitoring, and the effect of a brain tissue oxygen-directed critical care guide (PbtO(2)-CCG) on the 6-month clinical outcome (based on the 6-month Glasgow Outcome Scale score) in patients with TBIs. One hundred thirty-nine patients admitted to Creighton University Medical Center with major traumatic injuries (Injury Severity Scale [ISS] scores >or= 16) and TBI underwent prospective evaluation. All patients were treated with a PbtO(2)-CCG to maintain a brain oxygen level > 20 mm Hg, and control ICP < 20 mm Hg. The role of demographic, clinical, and imaging parameters in the identification of patients at risk for cerebral hypooxygenation and the influence of hypooxygenation on clinical outcome were recorded. Outcomes were compared with those in a historical ICP/CPP patient cohort. Subgroup analysis of severe TBI was performed and compared to data reported in the Traumatic Coma Data Bank. The majority of injuries were sustained in motor vehicle crashes (63%), and diffuse brain injury was the most common abnormality (58%). Mechanism of injury, severity of TBI, pathological entity, neuroimaging results, and trauma indices were not predictive of ischemia. Factors affecting death included gunshot injury, poor trauma indices, subarachnoid hemorrhage, and coma. After standard resuscitation, 65% of patients had an initially low PbtO(2). Data are presented as means +/- SDs. Treatment with the PbtO(2)-CCG resulted in a 44% improvement in mean PbtO(2) (16.21 +/- 12.30 vs 23.65 +/- 14.40 mm Hg; p < 0.001), control of ICP (mean 12.76 +/- 6.42 mm Hg), and the maintenance of CPP (mean 76.13 +/- 15.37 mm Hg). Persistently low cerebral oxygenation was seen in 37% of patients at 2 hours, 31% at 24 hours, and 18% at 48 hours of treatment. Thus elevated ICP and a persistent low PbtO(2) after 2 hours represented increasing odds of death (OR 14.3 at 48 hours). Survivors and patients with good outcomes generally had significantly higher mean daily PbtO(2) and CPP values compared to nonsurvivors. Polytrauma, associated with higher ISS scores, presented an increased risk of vegetative outcome (OR 9.0). Compared to the ICP/CPP cohort, the mean Glasgow Outcome Scale score at 6 months in patients treated with PbtO(2)-CCG was higher (3.55 +/- 1.75 vs 2.71 +/- 1.65, p < 0.01; OR for good outcome 2.09, 95% CI 1.031-4.24) as was the reduction in mortality rate (25.9 vs 41.50%; relative risk reduction 37%), despite higher ISS scores in the PbtO(2) group (31.6 +/- 13.4 vs 27.1 +/- 8.9; p < 0.05). Subgroup analysis of severe closed TBI revealed a significant relative risk reduction in mortality rate of 37-51% compared with the Traumatic Coma Data Bank data, and an increased OR for good outcome especially in patients with diffuse brain injury without mass lesions (OR 4.9, 95% CI 2.9-8.4). The prevention and aggressive treatment of cerebral hypooxygenation and control of ICP with a PbtO(2)-directed protocol reduced the mortality rate after TBI in major trauma, but more importantly, resulted in improved 6-month clinical outcomes over the standard ICP/CPP-directed therapy at the authors' institution.

Analogy Learning and the Performance of Motor Skills under Pressure

The efficacy of analogical instruction, relative to explicit instruction, for the acquisition of a complex motor skill and subsequent performance under pressure was investigated using a modified (seated) basketball shooting task. Differences in attentional resource allocation associated with analogy and explicit learning were also examined using probe reaction times (PRT). Access to task-relevant explicit (declarative) knowledge was assessed. The analogy and explicit learning groups performed equally well during learning and delayed retention tests. The explicit group experienced a drop in performance during a pressured transfer test, relative to their performance during a preceding retention test. However, the analogy group's performance was unaffected by the pressure manipulation. Results from PRTs suggested that both groups allocated equal amounts of attentional resources to the task throughout learning and test trials. Analogy learners had significantly less access to rules about the mechanics of their movements, relative to explicit learners. The results are interpreted in the context of Eysenck and Calvo's (1992) processing efficiency theory and Masters's (1992) theory of reinvestment.

Predictors of shunt during carotid endarterectomy with routine electroencephalography monitoring

The routine use of intraoperative electroencephalography (EEG) monitoring with selective shunt placement during carotid endarterectomy (CEA) has been shown to be safe and effective. We attempt to identify the anatomic and clinical factors associated with significant EEG changes requiring shunt placement during CEA. Between January 2005 and June 2007, 242 CEAs were performed with selective shunt placement for significant EEG changes. Risk factors assessed include severity of both ipsilateral and contralateral disease, presence of ipsilateral preoperative symptoms, hypertension, coronary artery disease, diabetes, age, gender, and preemptive intraoperative blood pressure manipulation to >or=20% above baseline before cross-clamping. Data were analyzed with the chi(2) test (P < .05 was significant). CEA was performed for asymptomatic disease in 177 of 242 patients (73.1%). The perioperative stroke rate was 0.8% (2 of 242), and the overall morbidity rate was 4.5%. No patients died. Significant EEG changes requiring shunt occurred in 35 patients (14.46%). Factors associated with carotid shunt placement were moderate ipsilateral carotid artery stenosis (50% to 79%) compared with severe (>or=80%) disease (30.6% vs 11.7%, P = .003) and degree of contralateral carotid stenosis (0% to 49%, 10.8%; 50% to 79%, 10.9%; 80% to 99%, 23.2%; occlusion, 50%; P = .0003). Presence of symptoms, gender, age, hypertension, diabetes, or coronary artery disease, and preemptive intraoperative manipulation of blood pressure were not significant predictors of shunt placement. CEA performed with routine EEG monitoring and selective shunt placement is associated with a low risk of perioperative stroke. Identified predictors of significant EEG changes were anatomic factors including degree of contralateral carotid artery disease and moderate ipsilateral carotid artery stenosis (50% to 79%). Although contralateral carotid occlusion has been accepted as indication for shunt placement in the absence of cerebral monitoring, this study suggests that high-grade contralateral disease and moderate ipsilateral carotid stenosis are associated with cerebral ischemia resulting in EEG changes and should prompt consideration for nonselective shunting.

Choking and excelling under pressure in experienced classifiers.

We extend previous work examining the effects of pressure on category learning to the effects of pressure on categorization performance in highly trained individuals. After extensive training on either a rule-based or an information-integration classification task, half of the participants performed the same task on a fifth day while under pressure to earn a monetary bonus ($50) for themselves and a partner. Performance of this group was compared with that of a low-pressure control group who performed without the pressure manipulation. Pressure caused performance decrements both for experienced classifiers performing rule-based tasks and for those performing information-integration tasks, as compared with control groups. These results contrast with those of previous research, where inexperienced classifiers choked on rule-based tasks but excelled on information-integration tasks. An additional "superpressure" block of trials was given at the end of the fifth session. Under this type of pressure, participants performing an information-integration task outperformed those performing rule-based tasks. Implications for theories of choking under pressure are discussed.

Advances in Emerging Therapies

Historically, stroke has proven to be a condition poorly amenable to treatment, and the last year delivered its share of neutral results in this regard. However, other studies suggested promising areas for pursuit while a couple grabbed the headlines and will modify clinical practice. We can justifiably emphasize the findings of the third European Cooperative Acute Stroke Study (ECASS-3), which has recently confirmed the use of thrombolytic therapy up to 4.5 hours after onset of ischemic stroke.1 The reality is that alteplase was already a safe and highly effective treatment before the results of ECASS-3 became known. However, a minority allowed their uncertainty over safety and doubts raised by individually neutral trials to restrict implementation of this potent therapy. The latest result broadens the range of patients who may benefit but it has implications beyond these narrow confines. Even after accounting for the expected low rate of symptomatic bleeding—just 2% excess over placebo—alteplase treatment delivered a 10% absolute increase in proportion of patients attaining excellent outcome, indicating 3 valuable lessons. First, any residual doubts over the safety or efficacy of intravenous alteplase early after stroke have been annulled. Second, the challenging time window for treatment can be relaxed, provided this is not at the expense of slower reaction by services. Third, there is evidently scope for further extension of treatment and enhancement of alteplase’s action that begs continued research. We need to test extended patient selection, perhaps via imaging strategies. We must also assess whether we can enhance the extent and rapidity of reperfusion. This may involve incoorporating ancillary measures such as antithrombotic therapy and blood pressure manipulation. One of our challenges is to divorce enhancement of reperfusion from exacerbation of serious bleeding risk. Both better patient selection and careful pharmacological profiling are required. By harnessing our very active …

Effects of baroreceptor activation on respiratory variability in rat

Controversy surrounds the respiratory responses to baroreceptor activation. Although many reflexes that effect respiration (e.g. chemoreflexes and nociceptive reflexes) frequently affect cardiovascular parameters, the effect of baroreflex stimulation within normal physiological limits is generally considered to affect only blood pressure and heart rate. Even though previous authors have reported that baroreceptor activation can affect respiratory activity, the effects on respiratory frequency and amplitude are highly variable, and changes in perfusion evoked by blood pressure manipulation could account for the observed effects. Here, we determined the respiratory effects of activating arterial baroreceptors by intravenous injection of phenylephrine or angiotensin II, or by electrical stimulation of the aortic depressor nerve (ADN). In urethane-anesthetized vagotomized rats, 1, 2 and 4s trains of tetanic ADN stimulation evoked 3.1+/-1.1%, 11.2+/-13.6% and 21.9+/-8.9% increases in inspiratory (TI) time and 26.5+/-18%, 23.4+/-15.7% and 34.6+/-20.9% increases in expiratory (TE) time, respectively (P<0.05 in both cases), but no effect on the amplitude of bursts recorded in the phrenic nerve. Similar effects were observed following pressor trials evoked by intravenous PE (TE: +26.1+/-9.1%, P<0.01), but not Ang II. Intermittent ADN stimulation (single pulse, 1 Hz) significantly increased the variability of TI during periods of low respiratory drive (P<0.05) without significantly affecting any other parameters. We propose that a specific baroreceptor-respiratory response exists that is independent of changes in blood flow. In contrast to the effects of baroreceptor stimulation on sympathetic nerve activity, the baro-respiratory response is subtle and highly dependent on respiratory drive.

Speaking one's second language under time pressure: An ERP study on verbal self‐monitoring in German–Dutch bilinguals

This study addresses how verbal self-monitoring and the Error-Related Negativity (ERN) are affected by time pressure when a task is performed in a second language as opposed to performance in the native language. German-Dutch bilinguals were required to perform a phoneme-monitoring task in Dutch with and without a time pressure manipulation. We obtained an ERN following verbal errors that showed an atypical increase in amplitude under time pressure. This finding is taken to suggest that under time pressure participants had more interference from their native language, which in turn led to a greater response conflict and thus enhancement of the amplitude of the ERN. This result demonstrates once more that the ERN is sensitive to psycholinguistic manipulations and suggests that the functioning of the verbal self-monitoring system during speaking is comparable to other performance monitoring, such as action monitoring.

Controlling Hypertension and Hypotension Immediately Post Stroke (CHHIPS) – a randomised controlled trial

To assess the effects of acute pressor and depressor blood pressure (BP) manipulation on 2-week death and dependency following acute stroke and investigate the safety and efficacy of such treatments. A multicentre, prospective, randomised, double-blind, placebo-controlled titrated-dose trial. Five hospitals in England. Patients over 18 years admitted to hospital with a clinical diagnosis of suspected stroke and either (1) symptom onset < 36 hours and hypertension, defined as systolic BP (SBP) < 160 mmHg (depressor arm), or (2) symptom onset < 12 hours and hypotension, defined as SBP < or = 140 mmHg (pressor arm). Patients were allocated to either the pressor or the depressor arm depending on blood pressure at randomisation. The ratio of allocation to active intervention versus matched placebo was 2:1 for the depressor arm and 1:1 for the pressor arm. The primary end point was death and dependency at 2 weeks, with dependency defined as a modified Rankin score < 3. Secondary end points were the safety of acute pressor (0-12 hours post stroke) and depressor (0-36 hours post stroke) BP manipulation in stroke patients; whether effects of BP reduction are influenced by stroke type (ischaemic versus haemorrhagic); whether alternative routes for administration of antihypertensive therapy (including sublingual and intravenous) are effective in dysphagic stroke patients; whether effects of BP manipulation are influenced by the time to treatment; and the short- and medium-term cost-effectiveness of such therapy in the acute post-stroke period on subsequent disability or death. 180 patients were recruited over the 36-month trial period, 179 in the depressor arm and one in the pressor arm (who received placebo). No significant difference was found in death or dependency at 2 weeks between those receiving active depressor treatment with lisinopril or labetalol and those receiving placebo, although numbers recruited to the trial were lower than projected. Active treatment was not associated with an increase in early neurological deterioration despite significantly greater reductions in BP at 24 hours and 2 weeks with active therapy compared with placebo. Active treatment was generally well tolerated and treatment discontinuation rates were similar in active and placebo groups. Survival analysis showed that the active treatment group had a lower mortality at 3 months than the placebo group (p = 0.05). The pressor arm was closed early because of problems with recruitment, so no conclusions can be drawn regarding this therapy. Oral and sublingual lisinopril and oral and intravenous labetalol are effective BP-lowering agents in acute cerebral infarction and haemorrhage and do not increase the likelihood of early neurological deterioration. The study was not sufficiently powered to detect a difference in disability or death at 2 weeks. However, the 3-month difference in mortality in favour of active treatment is of interest, although care must be taken in interpretation of the results. Further work is needed to confirm this and to assess whether there are differences in the effectiveness of labetalol compared with lisinopril in terms of reducing death or dependency after acute stroke, and whether the introduction of treatment post stroke earlier than was achieved here would be of greater benefit.

Parallel Constraint Satisfaction in Memory-Based Decisions

Three studies sought to investigate decision strategies in memory-based decisions and to test the predictions of the parallel constraint satisfaction (PCS) model for decision making (Glockner & Betsch, 2008). Time pressure was manipulated and the model was compared against simple heuristics (take the best and equal weight) and a weighted additive strategy. From PCS we predicted that fast intuitive decision making is based on compensatory information integration and that decision time increases with increasing inconsistency in the decision task. In line with these predictions we observed a predominant usage of compensatory strategies under all time pressure conditions and even with decision times as short as 1.7 seconds. For a substantial number of participants, choices and decision times were best explained by PCS, but there was also evidence for use of simple heuristics. The time pressure manipulation did not significantly affect decision strategies. Overall, the results highlight intuitive, automatic processes in decision making and support the idea that human information-processing capabilities are less severely bounded than often assumed.