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Older adults exposed to enriched environments (EE) maintain relatively higher levels of cognitive function, even in the face of compromised markers of brain health. Response speed (RS) is often used as a simple proxy to measure the preservation of global cognitive function in older adults. However, it is unknown which specific selection, decision, and/or motor processes provide the most specific indices of neurocognitive health. Here, using a simple decision task with electroencephalography (EEG), we found that the efficiency with which an individual accumulates sensory evidence was a critical determinant of the extent to which RS was preserved in older adults. Moreover, the mitigating influence of EE on age-related RS declines was most pronounced when evidence accumulation rates were shallowest. These results suggest that the phenomenon of cognitive reserve, whereby high EE individuals can better tolerate suboptimal brain health to facilitate the preservation of cognitive function, is not just applicable to neuroanatomical indicators of brain ageing, but can be observed in markers of neurophysiology. Our results suggest that EEG metrics of evidence accumulation may index neurocognitive vulnerability of the ageing brain.SIGNIFICANCE STATEMENTResponse speed in older adults is closely linked with trajectories of cognitive ageing. Here, by recording brain activity while individuals perform a simple computer task, we identify a neural metric which is a critical determinant of response speed. Older adults exposed to greater cognitive and social stimulation throughout a lifetime could maintain faster responding, even when this neural metric was impaired. This work suggests EEG is a useful technique for interrogating how a lifetime of stimulation benefits brain health in ageing.

Objectives:Mental fatigue, ‘brain fog’, and difficulties maintaining engagement are commonly reported issues in a range of neurological and psychiatric conditions. Traditional sustained attention tasks commonly measure this capacity as the ability to detect target stimuli based on sensory features in the auditory or visual domains. However, with this approach, discrete target stimuli may exogenously capture attention to aid detection, thereby masking deficits in the ability to endogenously sustain attention over time.Methods:To address this, we developed the Continuous Temporal Expectancy Task (CTET) where individuals continuously monitor a stream of patterned stimuli alternating at a fixed temporal interval (690 ms) and detect an infrequently occurring target stimulus defined by a prolonged temporal duration (1020 ms or longer). As such, sensory properties of target and non-target stimuli are perceptually identical and differ only in temporal duration. Using the CTET, we assessed stroke survivors with unilateral right hemisphere damage (N = 14), a cohort in which sustained attention deficits have been extensively reported.Results:Stroke survivors had overall lower target detection accuracy compared with neurologically healthy age-matched older controls (N = 18). Critically, stroke survivors performance was characterised by significantly steeper within-block performance decrements, which occurred within short temporal windows (˜3 ½ min), and were restored by the break periods between blocks.Conclusions:These findings suggest that continuous temporal monitoring taxes sustained attention processes to capture clinical deficits in this capacity over time, and outline a precise measure of the endogenous processes hypothesised to underpin sustained attention deficits following right hemisphere stroke.

Mental fatigue, ‘brain fog’ and difficulties maintaining engagement are commonly reported issues in a wide range of neurological and psychiatric conditions. These compromise the ability to effectively engage with rehabilitative intervention and limit plasticity processes necessary for optimal recovery. Traditional sustained attention tasks commonly measure this capacity as the ability to detect target stimuli based on sensory features in the auditory and visual domains. However, with this approach, discrete sudden onset target stimuli may exogenously capture attention and/or result in automatic stimulus-response mappings to aid target detection, thereby masking deficits in the ability to endogenously sustain attention over time. We have developed a sustained attention test (the continuous temporal expectancy test; CTET) which requires individuals to continuously monitor a stream of patterned stimuli alternating at a fixed temporal interval (690ms) and detect an infrequently occurring target stimulus defined by a prolonged temporal duration (1020ms or longer). Because sensory properties of target and non-target stimuli are perceptually identical and differ only in temporal duration, the CTET taxes continuous monitoring processes which are critical for sustaining attention. Here, using the CTET we assessed stroke survivors with unilateral right hemisphere damage (N=14), a cohort in which sustained attention deficits have been extensively reported. The right hemisphere stroke survivors had overall lower target detection accuracy on the CTET compared to neurologically-healthy age-matched older controls (N=18). In addition, performance of the stroke survivors was characterised by significantly steeper within-block performance decrements in target detection accuracy compared with controls. These decrements occurred within short temporal windows (∼3 ½ minutes) and were restored by the break periods between blocks. These findings outline a precise measure of the endogenous processes hypothesized to underpin deficits of sustained attention following right hemisphere stroke and suggest that continuous temporal monitoring may be a particularly sensitive way to capture clinical deficits in the capacity to sustain attention over time.

Objectives. We sought to determine the prognostic value of the admission electrocardiogram (ECG) in patients with unstable angina and non–Q wave myocardial infarction (MI).Background. Although the ECG is the most widely used test for evaluating patients with unstable angina and non–Q wave MI, little prospective information is available on its value in predicting outcome in the current era of aggressive medical and interventional therapy.Methods. ECGs with the qualifying episode of pain were analyzed in patients enrolled in the Thrombolysis in Myocardial Ischemia (TIMI) III Registry, a prospective study of patients admitted to the hospital with unstable angina or non–Q wave MI.Results. New ST segment deviation ≥1 mm was present in 14.3% of 1,416 enrolled patients, isolated T wave inversion in 21.9% and left bundle branch block (LBBB) in 9.0%. By 1-year follow-up, death or MI occurred in 11% of patients with ≥1 mm ST segment deviation compared with 6.8% of patients with new, isolated T wave inversion and 8.2% of those with no ECG changes (p < 0.001 when comparing ST with no ST segment deviation). Two other high risk groups were identified: those with only 0.5-mm ST segment deviation and those with LBBB, whose rates of death or MI by 1 year were 16.3% and 22.9%, respectively. On multivariate analysis, ST segment deviation of either ≥1 mm or ≥0.5 mm remained independent predictors of death or MI by 1 year.Conclusions. The admission ECG is very useful in risk stratifying patients with non–Q wave MI. The new criteria of not only ≥1-mm ST segment deviation but also ≥0.5-mm ST segment deviation or LBBB identify high risk patients, whereas T wave inversion does not add to the clinical history in predicting outcome.(J Am Coll Cardiol 1997;30:133–40)

A canine model was developed to record right (RV) and left ventricular (LV) volumes and high-fidelity pressures during acute pulmonary hypertension without the need for major surgery. In this study, new methodology was applied to record high-fidelity RV and LV pressures during cinemagnetic resonance imaging of the heart before and after acute pulmonary hypertension in six anesthetized intact dogs in which the pericardium and thorax were never disturbed by any surgical procedure. After pulmonary embolus, RV systolic pressure increased from 27 + 2 (SD) to 43 +/- 8 mmHg (P < 0.01) as LV systolic pressure decreased (97 +/- 17 to 76 +/- 3 mmHg; P < 0.05). Stroke volume (26 +/- 7 to 21 +/- 5 ml; P < 0.05) and RV ejection fraction (45 +/- 9 to 28 +/- 3%; P < 0.01) decreased as LV ejection fraction was unchanged (50 +/- 5 to 52 +/- 5%; P = NS). LV end-diastolic pressure decreased from 11 +/- 4 to 7 +/- 3 mmHg (P < 0.05), and RV end-diastolic pressure increased from 6 +/- 3 to 11 +/- 3 mmHg (P < 0.01). RV end-diastolic volume increased from 57 +/- 14 to 75 +/- 20 ml (P < 0.01) as LV end-diastolic volumes decreased from 53 +/- 11 to 42 +/- 10 ml (P < 0.01), resulting in no change in total ventricular volume at end diastole (111 +/- 24 to 116 +/- 28 ml). The observed mean decrease of 4.0 mmHg and 11 ml in LV end-diastolic pressure and volume, respectively, was associated with no change in total ventricular volume.(ABSTRACT TRUNCATED AT 250 WORDS)

UNLABELLED: RATIONALE, OBJECTIVE AND METHODS: The authors recently combined magnetic resonance imaging with high-fidelity left ventricular (LV) pressure measurement in a closed-chested, intact animal model. However, LV volumes derived from summated serial short axis slices require long imaging times and make it difficult to record LV volumes in response to acute alterations in load. In this study, geometry-based LV end-systolic volume estimates calculated from a single long-axis image (Area-Length formula) and from a long-axis and short-axis image (Bullet formula) were compared to those derived from summated short-axis images of the left ventricle (Simpson's rule) during altered loading conditions in six anesthetized, intact dogs. RESULTS: Angiotensin infusion produced three different LV systolic pressures (89 +/- 8 vs. 123 +/- 12 vs. 151 +/- 10 mmHg, P < .001). Area-Length and Bullet formula end-systolic volumes correlated with Simpson's rule volumes (r = .95 and .97; respectively). However, Bullet formula end-systolic volumes provided a significantly better agreement with Simpson's rule end-systolic volumes. CONCLUSIONS: The Bullet formula can be substituted for Simpson's rule to record magnetic resonance LV volumes during steady-state alterations in load in our intact animal model.

A canine model was developed to estimate left ventricular wall stress, volumes, contractility, and high-energy phosphate metabolites without the need for major surgery. A percutaneously inserted catheter-tip manometer was used to record high-fidelity left ventricular pressure while gradient echo cinemagnetic resonance (cine-MR) imaging alternated with in vivo 31P-nuclear magnetic resonance (NMR) spectroscopy during pharmacological maneuvers to increase cardiac work. Left ventricular circumferential wall stress, volumes, maximum rate of pressure development (dP/dtmax), and the ratio of phosphocreatine (PCr) to gamma-ATP (PCr/gamma-ATP) were recorded sequentially during control 1, dobutamine infusion, control 2, angiotensin infusion, and control 3 in five anesthetized, closed-chest dogs. PCr/gamma-ATP did not change significantly during controls 1-3, angiotensin, and dobutamine infusion. Left ventricular peak positive dP/dt (+dP/dtmax) increased significantly during dobutamine (3,338 +/- 831 mmHg/s, P < 0.001) but was unchanged during angiotensin (1,818 +/- 317 mmHg/s) and controls 1-3 (1,915 +/- 434 vs. 1,808 +/- 478 vs. 1,859 +/- 414 mmHg/s). However, dobutamine decreased the total systolic stress integral (area under the wall stress-time relationship) and end-diastolic and end-systolic volumes, whereas angiotensin increased these parameters compared with control conditions. The unchanged PCr/gamma-ATP is in accord with the results from other open-chest surface coil 31P-NMR experiments in the normal heart. Our assessment of left ventricular functional parameters provides new information that complements these more invasive studies in which heart rate-pressure product was measured during increases in cardiac work.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: Numerous models of acute and chronic left ventricular dysfunction have been used over the years. However, few can produce a rapid onset of global systolic and diastolic dysfunction that is stable and potentially reversible. The aim of this study was to develop such a model. Methods: A model of left ventricular dysfunction was produced in six intact dogs using 1% halothane anaesthesia and pharmacological autonomic blockade with atropine (0.1 mg·kg−1) and propranolol (2 mg·kg−1). Left ventricular function was assessed by combined high fidelity pressure and cinemagnetic resonance imaging (cine-MR) during increases in afterload using infusions of angiotensin. Results: Left ventricular systolic dysfunction was characterised by a diminished resting ejection fraction of 45(SD 4)% and a depressed +dP/dtmax of 1537(100) mm Hg·s−1. Diastolic dysfunction was manifested by an increased left ventricular end diastolic pressure of 16(2) mm Hg, a decreased −dP/dtmax of −1705(369) mm Hg·s−1, and a prolonged time constant of left ventricular relaxation of 42(9) ms. As left ventricular systolic pressure steadily rose with angiotensin infusion from 87(7) to 124(13) to 152(10) mm Hg (p

Previous work in the isolated heart and intact circulation has suggested that the relationship between wall stress and time during left ventricular (LV) ejection is linear and that the slope, which will be referred to as time-varying wall stress, increases in response to augmentation in afterload. However, the etiology of the increase in slope has not been determined in an intact animal. Magnetic resonance imaging coupled with high-fidelity LV pressure measurement using a nonferrous catheter-tip manometer generates a detailed assessment of wall stress in an animal model where the thorax and pericardium have never been disturbed. Accordingly, six anesthetized dogs were studied during autonomic blockade with atropine and propranolol during angiotensin infusion, producing three widely disparate left ventricular systolic pressures (87 +/- 7 vs. 124 +/- 13 vs. 152 +/- 10 mmHg, P less than 0.001). Time-varying wall stress did not change from low to medium load (-42.4 +/- 9.5 to -27.3 +/- 22.3 g.cm-2.ms-1) but increased significantly at high load (-21.7 +/- 14.9 g.cm-2.ms-1, P less than 0.05). Analysis of the relative contribution of pressure, chamber radius, wall thickness, and long-axis dimension to the changes in time-varying wall stress demonstrated only the pressure component to change its relative contribution at medium (P less than 0.001) and high load (P less than 0.001). Therefore, we conclude that the increase in time-varying wall stress results from augmentation of pressure in the latter one-half of systole that is incompletely offset by shortening and wall thickening.(ABSTRACT TRUNCATED AT 250 WORDS)

William Knott Pallister (“Bill”) was born in Sunderland in 1926, and at the age of 10 moved to Newport, Monmouthshire, where he attended Newport High School, excelling academically and in sport. He won an entrance scholarship to Westminster Medical School in 1944, where he qualified in 1949. He represented the medical school in rugby and cricket and …

To determine secretory IgA epitopes in tears of extended-wear soft contact lens wearers and non-wearing controls.We developed enzyme-linked immunosorbent assays (ELISA) to determine the tear concentrations of two epitopes of secretory IgA, the IgA alpha-chain and the secretory component. These epitopes were measured in basal tears of 20 individuals in 6 nights of extended wear of etafilcon A soft contact lenses and in 19 non-lens-wearing individuals.Levels of IgA alpha-chain immunoreactivity were significantly decreased in the lens-wearing group compared to non-lens wearers. However, the level of secretory component immunoreactivity was not significantly different between groups. IgA alpha-chain and secretory component immunoreactvity were highly correlated; however, some samples showed a marked variation between these two values.Tear concentrations of sIgA epitopes are significantly reduced in extended-wear contact lens wearers, and may contribute to the increased susceptibility to ocular infection seen in this group.

We sought to determine the prognostic value of the admission electrocardiogram (ECG) in patients with unstable angina and non-Q wave myocardial infarction (MI).Although the ECG is the most widely used test for evaluating patients with unstable angina and non-Q wave MI, little prospective information is available on its value in predicting outcome in the current era of aggressive medical and interventional therapy.ECGs with the qualifying episode of pain were analyzed in patients enrolled in the Thrombolysis in Myocardial Ischemia (TIMI) III Registry, a prospective study of patients admitted to the hospital with unstable angina or non-Q wave MI.New ST segment deviationor = 1 mm was present in 14.3% of 1,416 enrolled patients, isolated T wave inversion in 21.9% and left bundle branch block (LBBB) in 9.0%. By 1-year follow-up, death or MI occurred in 11% of patients withor = 1 mm ST segment deviation compared with 6.8% of patients with new, isolated T wave inversion and 8.2% of those with no ECG changes (p0.001 when comparing ST with no ST segment deviation). Two other high risk groups were identified: those with only 0.5-mm ST segment deviation and those with LBBB, whose rates of death or MI by 1 year were 16.3% and 22.9%, respectively. On multivariate analysis, ST segment deviation of eitheror = 1 mm oror = 0.5 mm remained independent predictors of death or MI by 1 year.The admission ECG is very useful in risk stratifying patients with non-Q wave MI. The new criteria of not onlyor = 1-mm ST segment deviation but alsoor = 0.5-mm ST segment deviation or LBBB identify high risk patients, whereas T wave inversion does not add to the clinical history in predicting outcome.

This study sought to examine the management and subsequent outcomes of patients with a prehospital electrocardiogram (ECG) in a large, voluntary registry of myocardial infarction.The prehospital ECG has been proposed as a means of rapidly identifying patients with acute myocardial infarction who might be eligible for reperfusion therapy.The characteristics and outcomes of patients with a prehospital ECG were compared with those without a prehospital ECG in the National Registry of Myocardial Infarction 2 data base. Included in the analysis were those patients who presented to the hospital within 12 h of an acute myocardial infarction. Excluded were patients with an in-hospital infarction, transferred-in referrals and self-transported patients.Prehospital ECGs were obtained in 3,768 (5%) of 66,995 National Registry of Myocardial Infarction 2 patients meeting study criteria. Median time from myocardial infarction symptom onset until hospital arrival was longer among those having a prehospital ECG (152 vs. 91 min, p0.001). However, once in the hospital, the prehospital ECG group experienced a shorter median time to the initiation of either thrombolysis (30 vs. 40 min, p0.001) or primary angioplasty (92 vs. 115 min, p0.001). The prehospital ECG group was more likely to receive thrombolytic therapy (43% vs. 37%, p0.001) and to undergo primary angioplasty (11% vs. 7%, p0.001). Also, the prehospital ECG group was more likely to undergo coronary arteriography (55% vs. 40%, p0.001), angioplasty (24% vs. 16%, p0.001) or bypass surgery (10% vs. 6%, p0.001). The in-hospital mortality rate was 8% in patients with a prehospital ECG and 12% in those without a prehospital ECG (p0.001). After adjusting for baseline covariates utilizing multiple logistic regression analysis, this mortality difference remained statistically significant (odds ratio 0.83, 95% confidence interval 0.71 to 0.96, p = 0.01).The prehospital ECG is infrequently utilized for diagnosing myocardial infarction, and among patients with a prehospital ECG, is associated with a longer time from symptom onset to hospital arrival. Despite these shortcomings, the prehospital ECG is a test that may potentially influence the management of patients with acute myocardial infarction through wider, faster in-hospital utilization of reperfusion strategies and greater usage of invasive procedures, factors that may possibly reduce shortterm mortality. Efforts to implement the prehospital ECG more widely and more rapidly may be indicated.

All materials were tested as either untreated films or coated with a 1st generation Biocompatibles coating based on phosphorylcholine (1) which aims to increase the haemocompatibility of a wide range of biomaterials.

A case of bilateral hydrothorax associated with catheterization of the internal jugular vein for feeding purposes is described. The possible mechanisms of this complication are discussed.

In a randomised trial postoperative pain relief was provided by either epidural injections of bupivacaine or an infusion of fentanyl adjusted by the patient to achieve adequate pain relief. Both techniques produced satisfactory analgesia without respiratory depression after peripheral arterial surgery. The technique of infusing intravenously a potent analgesic in a dose adjusted by the patient appears to offer several advantages in postoperative care.