Coupling the topological defect phase to the extrinsic curvature in nematic shells.

In two dimensional nematics, topological defects are point like singularities with both a charge and a phase. We study the topological defects within curved nematic textures on the surface of a cylinder. This allows us to isolate the effect of extrinsic curvature on the structure of the topological defect. By minimizing the energy associated with distortions in the nematic director around the core of a defect, we show that the phase of the topological defect is coupled to the orientation of the cylinder. This coupling depends on the relative energetic cost associated with splay, bend and twist distortions of the nematic director. We identify a bistability in the phase of the defects when twist deformations dominate. Finally, we show a similar effect for integer charge topological defects.

Lost in Time: Temporal Monitoring Elicits Clinical Decrements in Sustained Attention Post-Stroke.

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.

Orientational Correlations in Active and Passive Nematic Defects.

We investigate the emergence of orientational order among +1/2 disclinations in active nematic liquid crystals. Using a combination of theoretical and experimental methods, we show that +1/2 disclinations have short-range antiferromagnetic alignment, as a consequence of the elastic torques originating from their polar structure. The presence of intermediate -1/2 disclinations, however, turns this interaction from antialigning to aligning at scales that are smaller than the typical distance between like-sign defects. No long-range orientational order is observed. Strikingly, these effects are insensitive to material properties and qualitatively similar to what is found for defects in passive nematic liquid crystals.

Properties of twisted topological defects in 2D nematic liquid crystals.

Topological defects are one of the most conspicuous features of liquid crystals. In two dimensional nematics, they have been shown to behave effectively as particles with both charge and orientation, which dictate their interactions. Here, we study "twisted" defects that have a radially dependent orientation. We find that twist can be partially relaxed through the creation and annihilation of defect pairs. By solving the equations for defect motion and calculating the forces on defects, we identify four distinct elements that govern the relative relaxational motion of interacting topological defects, namely attraction, repulsion, co-rotation and co-translation. The interaction of these effects can lead to intricate defect trajectories, which can be controlled by setting relevant timescales.

Activity Driven Orientational Order in Active Nematic Liquid Crystals on an Anisotropic Substrate.

We investigate the effect of an anisotropic substrate on the turbulent dynamics of a simulated two-dimensional active nematic. This is introduced as an anisotropic friction and an effective anisotropic viscosity, with the orientation of the anisotropy being defined by the substrate. In this system, we observe the emergence of global nematic order of topological defects that is controlled by the degree of anisotropy in the viscosity and the magnitude of the active stress. No global defect alignment is seen in passive liquid crystals with anisotropic viscosity or friction confirming that ordering is driven by the active stress. We then closely examine the active flow generated by a single defect to show that the net kinetic energy of the flow is dependent on the orientation of the defect relative to the substrate, resulting in a torque on the defect to align it with the anisotropy in the substrate.

Geometrical Control of Active Turbulence in Curved Topographies.

We investigate the turbulent dynamics of a two-dimensional active nematic liquid crystal constrained to a curved surface. Using a combination of hydrodynamic and particle-based simulations, we demonstrate that the fundamental structural features of the fluid, such as the topological charge density, the defect number density, the nematic order parameter, and defect creation and annihilation rates, are approximately linear functions of the substrate Gaussian curvature, which then acts as a control parameter for the chaotic flow. Our theoretical predictions are then compared with experiments on microtubule-kinesin suspensions confined on toroidal droplets, finding excellent qualitative agreement.

Cellular geometry controls the efficiency of motile sperm aggregates.

Sperm that swim collectively to the fertilization site have been observed across several vertebrate and invertebrate species, with groups ranging in size from sperm pairs to massive aggregates containing hundreds of cells. Although the molecular mechanisms that regulate sperm-sperm adhesion are still unclear, aggregation can enhance sperm motility and thus offer a fertilization advantage. Here, we report a thorough computational investigation on the role of cellular geometry in the performance of sperm aggregates. The sperm head is modelled as a persistent random walker characterized by a non-trivial three-dimensional shape and equipped with an adhesive region where cell-cell binding occurs. By considering both, a simple parametric head shape and a computer reconstruction of a real head shape based on morphometric data, we demonstrate that the geometry of the head and the structure of the adhesive region crucially affects both the stability and motility of the aggregates. Our analysis further suggests that the apical hook commonly found in the sperm of muroid rodents might serve to shield portions of the adhesive region and promote efficient alignment of the velocities of the interacting cells.

The prehospital electrocardiogram in acute myocardial infarction: is its full potential being realized? National Registry of Myocardial Infarction 2 Investigators.

OBJECTIVES: 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. BACKGROUND: The prehospital ECG has been proposed as a means of rapidly identifying patients with acute myocardial infarction who might be eligible for reperfusion therapy. METHODS: 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. RESULTS: 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, p < 0.001). However, once in the hospital, the prehospital ECG group experienced a shorter median time to the initiation of either thrombolysis (30 vs. 40 min, p < 0.001) or primary angioplasty (92 vs. 115 min, p < 0.001). The prehospital ECG group was more likely to receive thrombolytic therapy (43% vs. 37%, p < 0.001) and to undergo primary angioplasty (11% vs. 7%, p < 0.001). Also, the prehospital ECG group was more likely to undergo coronary arteriography (55% vs. 40%, p < 0.001), angioplasty (24% vs. 16%, p < 0.001) or bypass surgery (10% vs. 6%, p < 0.001). The in-hospital mortality rate was 8% in patients with a prehospital ECG and 12% in those without a prehospital ECG (p < 0.001). 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). CONCLUSIONS: 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.

The electrocardiogram predicts one-year outcome of patients with unstable angina and non-Q wave myocardial infarction: results of the TIMI III Registry ECG Ancillary Study. Thrombolysis in Myocardial Ischemia.

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 > or = 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 > or = 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 > or = 1 mm or > 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 > or = 1-mm ST segment deviation but also > or = 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.

A stable model of left ventricular dysfunction in an intact animal assessed with high fidelity pressure and cinemagnetic resonance imaging.

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 < 0.001), left ventricular ejection fraction decreased markedly from 45(4) to 35(4) to 27(4)% (p < 0.001). Left ventricular +dP/dtmax did not change [1537(100) to 1500(110) to 1498(84) mm Hg.s-1] in spite of a significant increase in left ventricular end diastolic pressure from 16(2) to 21(5) to 29(7) mm Hg (p < 0.001) and left ventricular end diastolic volume from 59(12) to 71(14) to 78(17) ml (p < 0.001). Individual slopes of the end systolic pressure-volume relationship were also low, ranging between 2.1 and 4.4 mm Hg.s-1 (r = 0.99 to 1.00), typical of impaired contractility. CONCLUSIONS: Halothane anaesthesia in dogs pretreated with large amounts of propranolol and appropriate muscarinic cholinergic blockade produces a moderate decrease in baseline systolic and diastolic function in our intact dog model. However, left ventricular systolic function showed limited contractile reserve when challenged by physiological increases in systemic arterial pressure. Impaired systolic and diastolic function may, at least in part, be related to diminished activator calcium produced by halothane in addition to the well known negative inotropic action of beta adrenergic blockade.

Emergent behavioural phenotypes of swarming models revealed by mimicking a frustrated anti-ferromagnet.

Self-propelled particle (SPP) models are often compared with animal swarms. However, the collective animal behaviour observed in experiments often leaves considerable unconstrained freedom in the structure of a proposed model. Essentially, multiple models can describe the observed behaviour of animal swarms in simple environments. To tackle this degeneracy, we study swarms of SPPs in non-trivial environments as a new approach to distinguish between candidate models. We restrict swarms of SPPs to circular (periodic) channels where they polarize in one of two directions (like spins) and permit information to pass through windows between neighbouring channels. Co-alignment between particles then couples the channels (anti-ferromagnetically) so that they tend to counter-rotate. We study channels arranged to mimic a geometrically frustrated anti-ferromagnet and show how the effects of this frustration allow us to better distinguish between SPP models. Similar experiments could therefore improve our understanding of collective motion in animals. Finally, we discuss how the spin analogy can be exploited to construct universal logic gates, and therefore swarming systems that can function as Turing machines.

Comparison of biochemical markers of bone turnover in Paget disease treated with pamidronate and a proposed model for the relationships between measurements of the different forms of pyridinoline cross-links.

We have compared the use of new markers of bone turnover in the assessment and treatment of Paget disease and made observations on the mechanisms of bone resorption. Urine hydroxyproline (Hyp) as a bone resorption marker and serum alkaline phosphatase (ALP) as a bone formation marker have traditionally been used to biochemically assess and monitor treatment of Paget disease. Hyp and total ALP were compared with total urine pyridinoline (Pyd) and deoxypyridinoline (Dpd), free urine Pyd and Dpd, urine type I collagen N-terminal cross-linked telopeptide (NTX), type I collagen C-terminal propeptide (PICP), serum osteocalcin, and bone ALP in Paget patients treated with pamidronate. Patients were divided into three biochemical severity-based treatment groups by their fasting urine hydroxyprolline excretion (HypE) levels (Le., group 1, HypE < 5.0 mumol/l of glomerular filtrate [GF]; group 2, HypE of 5.0-9.9 mumol/l of GF; group 3, HypE > 10 mumol/l of GF). Group 1 received one 60 mg intravenous infusion of pamidronate, and groups 2 and 3 received four and six 60 mg infusions at weekly intervals, respectively. Fasting serum and morning urine specimens were taken before and at 2, 6, 13, and 26 weeks after starting treatment. Baseline Z scores were used to compare separation of patient results from normal, and the difference in Z scores from baseline to 13 weeks was used to compare response to treatment. Baseline discrimination and response to treatment at all disease activity levels was greatest for NTX and was poor for osteocalcin, PICP, and C-terminal cross-linked telopeptide of type I collagen (ICTP). The other markers showed good discrimination and response at medium and high levels of disease activity. NTX, total Pyd and Dpd, free Pyd and Dpd, and ICTP are all pyridinoline cross-link-based markers, but discrimination and response by NTX was generally much greater than for the others. Determination of the mechanism of the difference between NTX and other cross-link measures is necessary for appropriate use of the markers and may also lead to a better understanding of the bone resorption process. It has been proposed that the greater sensitivity and discrimination of NTX is because it is more bone-specific than the other cross-link markers with significant amounts of free Pyd and Dpd coming from nonbone sources. We propose another model where the proportion of peptide-bound cross-links such as NTX may be increased in high bone turnover states partly due to a rate-limiting step in their degradation to free cross-links. Conditions with high bone resorption rates would have high levels of NTX that would decline rapidly when resorption rates fall to a level where the capacity to degrade NTX matches the rate of production.

Assessment of ventricular volumes using cine magnetic resonance in the intact dog. A comparison of measurement methods.

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.

Right and left ventricular volumes and function after acute pulmonary hypertension in intact dogs.

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)

A maintenance protocol for psoriasis plaques cleared by the 308 nm excimer laser.

OBJECTIVE: Using the 308 nm excimer laser, to evaluate the effectiveness of tapering the dose frequency on maintaining the clearance of psoriasis plaques after at least 75% clearance of a target plaque was achieved. METHODS: This prospective case series, conducted at a university-based dermatology practice, enrolled five adults with stable, mild-to-moderate plaque-type psoriasis vulgaris. Patients received 308 nm UVB doses to affected areas. Initial dosing was based on multiples of a pre-determined minimal erythema dose (MED). Delivered fluences were 100, 150, 200, 250, 300 and 350 mJ/cm(2), corresponding to MED levels of 1 through 6. Subsequent doses were based on response to treatment. Induction treatments were scheduled biweekly for a total of 15 treatments. After improvement of disease, tapering began as follows: one treatment per week for 4 weeks, one treatment every other week for 4 weeks, and one final treatment 4 weeks later for a total of seven treatments. The main outcome measure was maintenance of disease improvement as determined by the Psoriasis Area and Severity Index (PASI) score and percentage improvement of target lesion and total body disease during and after the laser therapy taper. A flare was defined as a 25% worsening of the percentage improvement. RESULTS: All five patients completed the protocol. All patients achieved > or = 75% clearance of target plaques. No flares were noted upon completing the first month of the taper in any patient, either per percentage improvement or per PASI scores. One month after the second month of the taper (total of six treatments), no flares were noted and four out of five patients had no flares per PASI scores. No patients, either at the end of induction or at any interval during the taper, met the definition of a 50% rebound of PASI scores. Adverse effects included erythema, blisters, hyperpigmentation and erosions. All were well tolerated. CONCLUSION: Our results reaffirm that biweekly UVB laser treatments promote clearance of psoriatic plaques. A tapering of laser treatments may be beneficial in maintaining the level of plaque clearance obtained from biweekly laser treatments. Randomized, prospective trials are needed to establish laser therapy protocols for maintaining the plaque clearance achieved with the 308 nm excimer laser.

Class I topical corticosteroid use by psoriasis patients in an academic practice.

BACKGROUND: Psoriasis is a chronic skin disorder that can have a profound impact on the quality of life of patients. The treatment of psoriasis is complicated by the availability of numerous topical agents, systemic agents, and phototherapy. Of the topical preparations available, the ultra-high potency, or Class I steroids, have an important role in treating psoriasis. Their use is most appropriate for the treatment of plaques in regions excluding the face, axilla, groin and genitals. OBJECTIVE: The purpose of this study was to examine the prescribing patterns of Class I topical corticosteroids within a large academic dermatology practice for patients with all types of psoriasis. METHODS: A retrospective chart review of 650 patients with psoriasis from an academic dermatology practice was performed. Class I steroid use was defined as those patients who were observed to be currently using clobetasol propionate, halobetasol propionate, diflorasone, or augmented betamethasone dipropionate. RESULTS: A total of 79% of patients were prescribed topical steroids of any class while 46% of patients were prescribed a Class I steroid. In all, 58% of patients who received topical steroid therapy received a Class I agent; 11% of patients prescribed Class I steroids also received systemic therapy for their psoriasis. Conversely, 35% of patients who received systemic therapy were also receiving Class I topical therapy. DISCUSSION: In our department, Class I topical steroids are commonly used in the treatment of psoriasis. The superpotent topicals are often used as an adjunct to systemic therapy and will likely remain a mainstay of psoriasis therapy.

Respiratory acidosis and subcutaneous emphysema during laparoscopic cholecystectomy.

A case is presented of a healthy 69-year-old woman who underwent elective laparoscopic cholecystectomy under general anaesthesia. As surgery proceeded she developed hypercapnia (arterial blood PaCO2 = 100 mmHg) and a related respiratory acidosis (arterial blood pH 7.07). The cause was attributed to subcutaneous insufflation and absorption of CO2, directly related to the surgical pneumoperitoneum.

Pre-induction priming of the uterine cervix with oral prostaglandin E2 and a placebo.

A double blind study was undertaken to determine the effectiveness or oral prostaglandin E2 as a means of improving the pelvic score prior to induction of labour. 48 patients who were greater than 37 weeks gestation and who had Bishop scores of less than 6 entered the study. Ten tablets were given on an hourly regime. Of 25 patients in the prostaglandin group, 17 were considered successes (68.0%), whereas of 23 patients who received a placebo, 9 were successes (39.1%). No adverse effects were recorded. Prostaglandin E2 is therefore considered a safe and effective method for priming the unfavourable cervix prior to induction of labour.