Multi-stabilities and symmetry-broken one-colour and two-colour states in closely coupled single-mode lasers

We theoretically investigate the dynamics of two mutually coupled identical single-mode semi-conductor lasers. For small separation and large coupling between the lasers, symmetry-broken one-colour states are shown to be stable. In this case the light output of the lasers have significantly different intensities while at the same time the lasers are locked to a single common frequency. For intermediate coupling we observe stable symmetry-broken two-colour states, where both lasers lase simultaneously at two optical frequencies which are separated by up to 150~GHz. Using a five dimensional model we identify the bifurcation structure which is responsible for the appearance of symmetric and symmetry-broken one-colour and two-colour states. Several of these states give rise to multi-stabilities and therefore allow for the design of all-optical memory elements on the basis of two coupled single-mode lasers. The switching performance of selected designs of optical memory elements is studied numerically.Comment: 12 pages, 15 figure

P-67: Dose response antihypertensive efficacy of aliskiren (SPP 100), an orally active renin inhibitor

Aliskiren (SPP 100), an orally active renin inhibitor, has been shown to inhibit the production of angiotensin I and angiotensin II in healthy volunteers. In a pilot study, aliskiren decreased BP in hypertensive patients at daily doses of 75 and 150 mg. In this multi-centre, double-blind, active comparator trial, the dose-dependent effects of aliskiren were evaluated in 226 patients with mild to moderate hypertension. Parallel groups of randomized patients were assessed at the end of a washout period and again after a 4-week treatment period. Treatment consisted of single oral daily doses of aliskiren (37.5, 75, 150 or 300 mg) or of losartan 100 mg once daily. Daytime ambulatory systolic BP was defined as the primary variable of the study. As illustrated in the figure, a clear dose-response curve was observed for the decrease (mean +/- SEM) in daytime ambulatory systolic BP. The mean (SD) change at the end of the 4-week treatment period was -1.3 (9.5) mmHg, -5.5 (10.6) mmHg, -8.5 (10.4) mmHg, -10.5 (10.7) mmHg, and -11.1 (13.4) mmHg for 37.5, 75, 150, and 300 mg aliskiren and 100mg losartan, respectively. Statistically significant lowering occurred with 75, 150 and 300 mg of aliskiren. The daytime ambulatory systolic BP responses to aliskiren doses of 150 and 300 mg were not significantly different from that of 100 mg losartan. Similar results were shown for daytime ambulatory diastolic BP and for night-time ambulatory systolic and diastolic BP. Aliskiren was well tolerated - there was no increase in the number of adverse events with increasing doses of aliskiren, and the safety profile of aliskiren was similar to that of losartan. The results of this dose-ranging study confirm a dose-dependent reduction in BP with aliskiren in mild to moderate hypertension. Additional exploratory studies testing the efficacy and safety of this new renin inhibitor in patients with renal disease and congestive heart failure are currently underwa

Effects of Aging and Hypertension on Plasma Angiotensin II and Platelet Angiotensin II Receptor Density

Plasma renin activity (PRA) declines with age in normal individuals, but the effect of age on plasma angiotensin II (ANG II) is less clear. A decline in plasma ANG II with age could result in altered platelet ANG II receptor density since plasma hormone levels influence their target organ receptors. To investigate this possibility, PRA, plasma ANG II, and platelet ANG II receptor density were examined in 17 young, 12 middle-aged, and 14 elderly healthy normotensive volunteers. To assess whether hypertension altered receptor density, these variables were also examined in 23 hypertensive patients. In normotensives, there was a negative correlation between age and PRA (r = — 0.43, P < .05), no significant change in basal plasma ANG II with age, and a weak positive correlation between age and ANG II receptor density (r = 0.34, P < .05). Multiple regression analysis revealed that the relationship between age and ANG II receptor density was independent of the associated rise in mean arterial arterial pressure with age (P < .05). Platelet ANG II receptor density was not significantly related to PRA or plasma ANG II. ANG II receptor affinity did not change with age. Neither PRA nor ANG II receptor density or affinity differed between hypertensives and normotensives of similar mean age, but plasma ANG II was significantly lower in hypertensives compared with normotensives. We concluded that aging is associated with a decline in supine PRA. The small decrease in plasma ANG II was not significant. Platelet ANG II receptor density increased with age primarily due to a small group of elderly subjects with elevated receptor density. There was no change in ANG II receptor density or affinity in hypertensives despite apparently lower plasma ANG II in these patients. Am J Hypertens 1992;5:687-69

Regression of left ventricular mass in hypertensive patients treated with perindopril/indapamide as a first-line combination: The REASON echocardiography study

Background: Increase in left ventricular mass (LVM) may be linked to morbidity and mortality in hypertensive patients. Arterial stiffness, systolic blood pressure (BP), and pulse pressure (PP) seem to be the main determinants of LVM. The perindopril/indapamide combination normalizes systolic BP, PP, and arterial function to a greater extent than atenolol. The aim of this study was to compare the effects of perindopril (2 mg)/indapamide (0.625 mg) first-line combination with atenolol (50 mg) on LVM reduction in hypertensive patients. Methods: Two hundred fourteen patients with essential hypertension participating in the PREterax in Regression of Arterial Stiffness in a ContrOlled Double-BliNd (REASON), randomized, double-blind, parallel-group study, underwent M-mode two-dimensional-guided echocardiography. Results: Perindopril/indapamide and atenolol were both effective at brachial BP reduction during the 12-month period. The systolic BP reduction was significantly greater with perindopril/indapamide than with atenolol (−21.2 v −15.3 mm Hg), whereas the reduction in diastolic BP was similar between treatment groups (−12.1 v −11.3 mm Hg). Reduction in LVM was higher with perindopril/indapamide than with atenolol. The between-group difference was significant for LVM (−13.6 v −4.3 g, P = .027), LVM/body surface area (LVMI1, P = .032), and LVM/body height2.7 (LVMI2, P = .013). The 124 patients with LV hypertrophy at baseline showed greatest LVM regression (LVM: −22.5 v −8.9 g, P = .009; LVMI1, P = .031; LVMI2, P = .028). The reduction in LVM adjusted for brachial systolic BP and heart rate was still significantly greater with perindopril/indapamide than with atenolol. Conclusions: Treatment, based on a first-line perindopril/indapamide combination in hypertensive patients, was more effective than atenolol on regression of echocardiographic indices of LVM and LV hypertroph

Twenty-four-hour ambulatory blood pressure monitoring efficacy of perindopril/indapamide first-line combination in hypertensive patients: the REASON study

Background: Circadian blood pressure (BP) measurements provide more information on hypertensive complications than office BP measurements. The purpose of this study was to analyze the efficacy of the first-line combination of perindopril 2 mg plus indapamide 0.625 mg versus atenolol 50 mg on BP parameters and variability over 24 h in patients with hypertension. Methods: A double-blind, randomized, controlled, 12-month study comparing perindopril/indapamide and atenolol was performed in 201 patients (age 55.0 years) with uncomplicated sustained essential hypertension. Ambulatory BP measurements (ABPM) were done every 15 min over 24 h. Results: After 1 year of treatment, the decrease in systolic BP was significantly greater for perindopril/indapamide than for atenolol during the entire 24-h period (-13.8 ν −9.2 mm Hg), the daytime and the nighttime periods (P < .01). Diastolic blood pressure (DBP) variations were comparable for the two groups (−7.2 ν −8.3 mm Hg, NS). Pulse pressure (PP) reduction was also significantly greater for perindopril/indapamide than for atenolol (for the whole 24 h, −6.6 ν −0.9 mm Hg, P < .001). The through to peak (T/P) BP ratio and the smoothness index were comparable in the two groups for DBP. For systolic blood pressure (SBP), higher values of the T/P ratio (0.80 ν 0.59) and the smoothness index (1.45 ν 0.98; P < .02) were achieved for the perindopril/indapamide combination than for atenolol. Conclusions: The perindopril/indapamide first-line combination decreased SBP and PP more effectively than atenolol. Moreover, the BP control effect was smooth and consistent throughout the 24-h dosing interval and BP reduction variability was lower than the one induced by atenolo

A text become provisional: revisiting the capital of the ruins

This essay is a reexamination of Samuel Beckett's The Capital of the Ruins, the untransmitted radio script written for Raidió Éireann (now Raidió Teilifís Éireann) in 1946 following his work with the Irish Red Cross in Saint Lô. The first half of this essay is concerned with the archival and publishing history of the text. This section examines the variants introduced by various editors or publishers and makes a case for a definitive edition of the text based on the edited photocopy of the typescript held in the Beckett International Foundation archive at the University of Reading. The second half of this essay then uses this close attention to the text to reconsider the focus of The Capital of the Ruins and the extent to which the piece is more firmly directed towards socio-political aspects of post-neutrality Ireland than has previously been identified

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Longitudinal Synaptic Loss in Primary Tauopathies: An In Vivo [11 C]UCB-J Positron Emission Tomography Study

BACKGROUND: Synaptic loss is characteristic of many neurodegenerative diseases; it occurs early and is strongly related to functional deficits. OBJECTIVE: In this longitudinal observational study, we determine the rate at which synaptic density is reduced in the primary tauopathies of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), and we test the relationship with disease progression. METHODS: Our cross-sectional cohort included 32 participants with probable PSP and 16 with probable CBD (all amyloid-negative corticobasal syndrome), recruited from tertiary care centers in the United Kingdom, and 33 sex- and age-matched healthy control subjects. Synaptic density was estimated by positron emission tomography imaging with the radioligand [11 C]UCB-J that binds synaptic vesicle 2A. Clinical severity and cognition were assessed by the PSP Rating Scale and the Addenbrooke's cognitive examination. Regional [11 C]UCB-J nondisplaceable binding potential was estimated in Hammersmith Atlas regions of interest. Twenty-two participants with PSP/CBD had a follow-up [11 C]UCB-J positron emission tomography scan after 1 year. We calculated the annualized change in [11 C]UCB-J nondisplaceable binding potential and correlated this with the change in clinical severity. RESULTS: We found significant annual synaptic loss within the frontal lobe (-3.5%, P = 0.03) and the right caudate (-3.9%, P = 0.046). The degree of longitudinal synaptic loss within the frontal lobe correlated with the rate of change in the PSP Rating Scale (R = 0.47, P = 0.03) and cognition (Addenbrooke's Cognitive Examination-Revised, R = -0.62, P = 0.003). CONCLUSIONS: We provide in vivo evidence for rapid progressive synaptic loss, correlating with clinical progression in primary tauopathies. Synaptic loss may be an important therapeutic target and outcome variable for early-phase clinical trials of disease-modifying treatments. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society