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This paper discusses the response of the economics profession to a possible occurrence of tipping points in natural systems, with a drop in welfare. For a climate tipping point, the hazard-rate model is relevant, and the paper shows that in a Ramsey growth model with climate tipping, the effect on policy is increased saving and increased taxation of greenhouse gas emissions. Climate change is often seen as a tragedy of the commons because incentives to deviate undermine cooperation and prevention of climate change. However, a climate tipping point can be prevented in a Nash equilibrium or with partial cooperation if the drop in welfare is sufficiently high. In case of uncertainty about the threshold, this result remains if the uncertainty is not too large. In the conclusion, the paper makes a few remarks on including tipping points in teaching environmental and resource economics.

Aims In the Ongoing Telmisartan Alone and in Combination with Ramipril Trial (ONTARGET), dual agent renin-angiotensin-aldosterone system (RAAS) blockade with angiotensin-converting-enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) did not reduce the risk of renal and cardiovascular outcomes compared with the single use of either agent. Dual therapy however increased the incidence of hyperkalemia. We examined risk factors for hyper- and hyokalemia and hypothesized that both would be associated with worse cardiovascular and renal outcomes.Methods A post-hoc analysis of the ONTARGET trial comparing dual therapy (ramipril andtelmisartan) vs monotherapy (ramipril ortelmisartan) was performed. The association between serum potassium at week 6 on cardiovascular and renal outcomes during the 56 months follow-up was assessed by multivariate Cox analysis. The main cardiovascular outcome was the composite of cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure. The renal outcome was defined as the composite of a doubling of serum creatinine or chronic dialysis.Results Six weeks after randomization, hyperkalemia developed in 210 (2.7%) patients on dual therapy vs 264 (1.6%) patients on monotherapy (p< 0.001 vs dual therapy). Hypokalemia developed in 87 (1.1%) patients on dual therapy vs 200 (1.2%)patients on monotherapy. Serum potassium was nonlinearly associated with cardiovascular and renal events with a nadir between 4.0–5.0 mmol/l for cardiovascular and 4.0–4.5 mmol/l for renal events such that subjects above or below these values exhibited higher risks. This association was independent of age, gender, diabetes, estimated glomerular filtration rate, systolic blood pressure and diuretic use.Conclusions With the precautions stipulated by the protocol of the ONTARGET trial, hypokalemia and hyperkalemia were infrequent events. Nevertheless, both high and low serum potassium were associated with an increased risk of cardiovascular and renal disease.

We present two-dimensional line-of-sight stellar kinematics of the lens galaxy in the Einstein Cross, obtained with the GEMINI 8 m telescope, using the GMOS integral-field spectrograph. The stellar kinematics extend to a radius of 4'' (with 0.''2 spaxels), covering about two-thirds of the effective (or half-light) radius Re [?] 6'' of this early-type spiral galaxy at redshift zl [?] 0.04, of which the bulge is lensing a background quasar at redshift zs [?] 1.7. The velocity map shows regular rotation up to [?]100 km s-1 around the minor axis of the bulge, consistent with axisymmetry. The velocity dispersion map shows a weak gradient increasing toward a central (R < 1'') value of s0 = 170 +- 9 km s-1. We deproject the observed surface brightness from Hubble Space Telescope imaging to obtain a realistic luminosity density of the lens galaxy, which in turn is used to build axisymmetric dynamical models that fit the observed kinematic maps. We also construct a gravitational lens model that accurately fits the positions and relative fluxes of the four quasar images. We combine these independent constraints from stellar dynamics and gravitational lensing to study the total mass distribution in the inner parts of the lens galaxy. We find that the resulting luminous and total mass distribution are nearly identical around the Einstein radius RE = 0.''89, with a slope that is close to isothermal, but which becomes shallower toward the center if indeed mass follows light. The dynamical model fits to the observed kinematic maps result in a total mass-to-light ratio Udyn = 3.7 +- 0.5 U,I (in the I band). This is consistent with the Einstein mass ME = 1.54 x 1010 M divided by the (projected) luminosity within RE , which yields a total mass-to-light ratio of U E = 3.4 U,I , with an error of at most a few percent. We estimate from stellar population model fits to colors of the lens galaxy a stellar mass-to-light ratio U[?] from 2.8 to 4.1 U,I . Although a constant dark matter fraction of 20% is not excluded, dark matter may play no significant role in the bulge of this [?]L [?] early-type spiral galaxy.

ABSTRACTObjectives:We performed a cost-consequence analysis in a French setting of the renoprotective benefit of irbesartan in hypertensive type 2 diabetes patients over a 25-year period.Research design and methods:A previously published Markov model simulated progression from microalbuminuria to overt nephropathy, doubling of serum creatinine, end-stage renal disease and death. Three treatment strategies with analogous blood pressure control were compared: (A) control – conventionally medicated antihypertensive therapy (excluding angiotensin converting enzyme inhibitors, other angiotensin-2-receptor antagonists and dihydropyridine calcium channel blockers) initiated at microalbuminuria; (B) early irbesartan – (300 mg daily added to control, initiated with microalbuminuria) and (C) late irbesartan – (300 mg daily, initiated with overt nephropathy). Probabilities came from the Irbesartan in Reduction of Microalbuminuria-2 study, Irbesartan in Diabetic Nephropathy Trial and other sources. Clinical and economic outcomes were projected over 25 years. Annual discount rates were 3%.Results:Compared to control, early use of irbesartan added (mean ± standard deviation) 1.51 ± 0.08 undiscounted life years (discounted: 0.94 ± 0.05 years), while late irbesartan added 0.07 ± 0.01 (0.04 ± 0.01) years/patient. Early irbesartan added 1.03 ± 0.06 discounted quality-adjusted life years (QALYs), while late irbesartan added 0.06 ± 0.01 QALYs. Early and late irbesartan treatments were projected to save €22 314 ± 1273 and €6619 ± 820/patient, respectively versus control. Sensitivity analysis showed that even over short time horizons both irbesartan treatments were superior to the control group.Conclusions:In France, early irbesartan treatment improved quality and length of life and reduced costs in hypertensive patients with type 2 diabetes and microalbuminuria. Late irbesartan therapy is beneficial, but earlier irbesartan leads to better outcomes.

We construct orbit-based axisymmetric dynamical models for the globular cluster M15 that fit ground-based line-of-sight velocities and Hubble Space Telescope line-of-sight velocities and proper motions. This allows us to constrain the variation of the mass-to-light ratio M/L as a function of radius in the cluster and to measure the distance and inclination of the cluster. We obtain a best-fitting inclination of 60deg +- 15deg, a dynamical distance of 10.3 +- 0.4 kpc, and an M/L profile with a central peak. The inferred mass in the central 0.05 pc is 3400 M, implying a central density of at least 7.4 x 106 M pc-3. We cannot distinguish the nature of the central mass concentration. It could be an intermediate mass black hole, or it could be a large number of compact objects, or it could be a combination. The central 4'' of M15 appears to contain a rapidly spinning core, and we speculate on its origin.

Zusammenfassung Hintergrund: Das obstruktive Schlafapnoesyndrom (OSAS) wird als unabhängiger kardiovaskulärer Risikofaktor diskutiert. Zentrale Apnoen mit Cheyne-Stokes-Atmung wiederum sind Folgen einer kongestiven Herzinsuffizienz und von prognostischer Bedeutung. Fallbeschreibung: Berichtet wird über den Fall eines 74-jährigen Patienten mit langjähriger nasaler Continuous-Positive-Airway-Pressure-Therapie wegen eines bekannten OSAS. In einer Kontrollpolysomnographie zeigten sich neu aufgetretene zentrale Apnoen vom Typ der Cheyne-Stokes-Atmung ohne Zeichen einer manifesten Herzinsuffizienz. In weiteren Untersuchungen stellte sich eine neu diagnostizierte hochgradige Aortenklappenstenose mit guter linksventrikulärer Funktion dar. Klinische Zeichen einer kongestiven Herzinsuffizienz wurden erst 2 Wochen nach dem ersten Auftreten von Cheyne-Stokes Atmung beobachtet. Schlussfolgerung: Cheyne-Stokes-Atmung kann infolge einer akuten kardialen Dekompensation schon vor den ersten klinischen Zeichen einer Herzinsuffizienz auftreten und sollte immer Anlass zu einer weiteren Abklärung sein. Anhand des Fallberichts wird das gegenwärtige pathophysiologische Verständnis der Cheyne Stokes Atmung resümiert.

Whiplash-associated disorders (WAD) are a major problem in the Western world, which put a formidable financial burden on modern society and which evoke an emerging debate on the true nature of their origin. To date there is no generally accepted test that allows us to diagnose WAD objectively. Because whiplash injury causes dysfunction of proprioception in the neck, we investigated the characteristics of the cervico-ocular reflex (COR) of presumptive WAD patients. These patients and age-matched healthy controls were rotated at different stimulus peak velocities in the dark while their head was fixed in space. The gain values of the COR were significantly increased in the patient population at a wide range of stimulus peak velocities with maximum difference at the lower frequencies (p = 0.037, ANOVA). Hence, although larger numbers of patients should be measured, the COR gain appears to be a parameter that may permit an objective diagnosis of WAD.

We present a summary of high-spatial resolution follow-up observations of the elliptical (E) and lenticular (S0) galaxies in the SAURON survey using the OASIS integral field spectrograph. The OASIS observations explore the central 8" × 10" regions of these galaxies using a spatial sampling four times higher than SAURON, often revealing previously undiscovered features. Around 75% (31/48) of the SAURON E/S0s with central velocity dispersion ≳ 120 km s⁻¹ were observed with OASIS, covering well the original SAURON representative sample.We present here an overview of this follow-up survey, and some preliminary results on individual objects, including a previously unreported counter-rotating core in NGC4382; the decoupled stellar and gas velocity fields of NGC2768; and the strong age gradient towards the centre of NGC3489. (© 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

There is growing evidence from clinical trials that losartan (Avastar™, Merck & Co., Inc.) and other angiotensin (A)-II-receptor antagonists have beneficial effects on the progression of renal disease among Type 2 diabetic patients beyond the benefits derived from the effect of blood-pressure lowering alone. Comparators used is the studies were not angiotensin-converting enzyme-inhibitors but typically conventional hypertensive therapy plus placebo, placebo alone and in one case, amlodipine. These trials have reported reductions in progression to end stage renal disease (ESRD) (losartan and irbesartan) and to nephropathy (irbesartan). An important pharmacoeconomic question is whether potential cost-savings on reduced progression to ESRD and nephropathy outweigh the extra costs of A-II-antagonist treatment. This paper will review the published economic studies for A-II-receptor antagonists and their pharmacoeconomic implications. In particular, potential pharmacoeconomic implications and related methodological aspects of the recent RENAAL trial for losartan are considered.

Zusammenfassung. qHintergrund: Die Lebensqualität bei Patienten mit obstruktivem Schlafapnoesyndrom (OSAS) vor und unter Therapie ist im Hinblick auf Langzeiteffekte bislang nur wenig untersucht. qPatienten und Methodik: In der vorliegenden Studie wurde die Veränderung der Lebensqualität mit Hilfe der Visuellen Analogskala (VAS) Lebensqualität, des Nottingham Health Profile (NHP) und des Quality of Life Index (QL-Index) bei 85 Patienten mit polysomnographisch gesichertem OSAS erfasst. Verglichen wurden die Ergebnisse der dauerhaften Therapieanwender (n = 66) mit denen der Studienteilnehmer (n = 19), die zum Zeitpunkt der Kontrolluntersuchung die Continuous-Positive-Airway-Pressure-(CPAP-)Therapie abgebrochen hatten. qErgebnisse: Sowohl die VAS (vor CPAP 56,9 ± 27,0, unter CPAP 67,2 ± 21,8 mm; p = 0,027) als auch die Dimensionen "Energieverlust" (vor CPAP 44,2 ± 39,5, unter CPAP 25,0 ± 34,2 Punkte; p &lt; 0,001), "Emotionale Reaktion" (vor CPAP 24,7 ± 22,5, unter CPAP 11,8 ± 18,8 Punkte; p &lt; 0,001) und "Schlafprobleme" (vor CPAP 32,0 ± 30,0, unter CPAP 21,5 ± 27,2 Punkte; p = 0,005) des NHP zeigten nach einer Beobachtungszeit von 16 ± 9 Monaten eine signifikante Besserung der Lebensqualität in der Gruppe der Therapieanwender. Für die Therapieabbrecher ergaben sich hingegen in sämtlichen verwendeten Instrumenten keine signifikanten Veränderungen. Eine Korrelation zwischen der durchschnittlichen nächtlichen Nutzungsdauer (Maskenstunden) und der Verbesserung der Lebensqualität fand sich nicht. qSchlussfolgerung: Möglicherweise ist schon eine scheinbar suboptimale Nutzung des CPAP-Gerätes ausreichend. Da nicht alle Instrumente bzw. deren Dimensionen zur Erfassung der Lebensqualität bei Patienten mit OSAS geeignet sind, ist die Entwicklung deutschsprachiger, krankheitsspezifischer Instrumente notwendig. Abstract. qBackground: Only poor data regarding changes in quality of life in patients with obstructive sleep apnea syndrome (OSAS) under continuous positive airway pressure (CPAP) therapy concerning long-term effects are available. qPatients and Methods: In this study, 85 patients were evaluated before and under CPAP therapy using the Visual Analog Scale (VAS) Quality of Life, the Nottingham Health Profile (NHP), and the Quality of Life Index (QL-Index). The results of patients with continuous usage of CPAP (n = 66) were compared with a control group of patients who discontinued CPAP therapy (n = 19). qResults: VAS (before CPAP 56.9 ± 27.0, under CPAP 67.2 ± 21.8 mm; p = 0.027) as well as the NHP dimensions "Energy" (before CPAP 44.2 ± 39.5, under CPAP 25.0 ± 34.2 points; p &lt; 0.001), "Emotional reactions" (before CPAP 24.7 ± 22.5, under CPAP 11.8 ± 18.8 points; p &lt; 0,001), and "Sleep problems" (before CPAP 32.0 + 30.0, under CPAP 21.5 + 27.2 points; p = 0.005) showed a significant improvement after 16 ± 9-month follow-up. In the control group, none of the instruments displayed a significant change. A correlation between CPAP compliance (mask hours) and changes in quality of life was not detected. qConclusion: Thus, even suboptimal CPAP usage might bring benefit regarding quality of life. As not all health-related instruments or dimensions were able to display the effects on quality of life, there is a need to translate and validate disease-specific instruments into the German language.

In some domains acquiring knowledge has proved successful in ways that have not been equalled elsewhere notwithstanding long-term efforts. As the lack of success in the latter must be due to the combination of approach and content, this suggests searching for new approaches, and interpreting the 'not' as a possibly 'never'. The alternative is to see the 'not' as a 'not yet'. The argument Von Foerster (1970) brings to this dilemma is that in the social domain the 'not' is due to an extra, mainly action-bound, source of variation. Constraining this source will allow for a (reasonable) 'not yet'. To remind of Heinz's surprising and sophisticated argument it is re-used.

1 We recently demonstrated that intracellular application of Angiotensin II (Angiotensin IIintr) induces rat aorta contraction independent of plasma membrane Angiotensin II receptors. In this study we investigated the effects of Angiotensin IIintr on cell growth in A7r5 smooth muscle cells. 2 DNA-synthesis was increased dose-dependently by liposomes filled with Angiotensin II as measured by [3H]-thymidine incorporation at high (EC50=27±6 pM) and low (EC50=14±5 nM) affinity binding sites with increases in Emax of 58±4 and 37±4% above quiescent cells, respectively. Cell growth was corroborated by an increase in cell number. 3 Extracellular Angiotensin II (10 pM – 10 μM) did not modify [3H]-thymidine incorporation. 4 Growth effects of Angiotensin IIintr mediated via high affinity sites were inhibited by liposomes filled with 1 μM of the non-peptidergic antagonists losartan (AT1-receptor) or PD123319 (AT2-receptor) or with the peptidergic agonist CGP42112A (AT2-receptor). Emax values were decreased to 30±3, 29±4 and 4±2%, respectively, without changes in EC50. The Angiotensin IIintr effect via low affinity sites was only antagonized by CGP42112A (Emax=11±3%), while losartan and PD123319 increased Emax to 69±4%. Intracellular applications were ineffective in the absence of Angiotensin IIintr. 5 Neither intracellular nor extracellular Angiotensin I (1 μM) were effective. 6 The Angiotensin IIintr induced growth response was blocked by selective inhibition of phosphatidyl inositol 3-kinase (PI-3K) by wortmannin (1 μM) and of the mitogen-activated protein kinase (MAPK/ERK) pathway by PD98059 (1 μM) to 61±14 and 4±8% of control, respectively. 7 These data demonstrate that Angiotensin IIintr induces cell growth through atypical AT-receptors via a PI-3K and MAPK/ERK -sensitive pathway. British Journal of Pharmacology (2001) 132, 1590 – 1596

We have analyzed V, H, and J Hubble Space Telescope (HST) images for a sample of early- to late-type spiral galaxies and have reported elsewhere the statistical frequency of R1/4-law and exponential bulges in our sample as a function of Hubble type and the frequency of occurrence and structural properties of the resolved central nuclei hosted by intermediate- to late-type bulges and disks (see references in the text). Here we use these data to show the following: The V-H color distribution of the R1/4 bulge peaks around [?]V-H[?] ~ 1.3, with a sigma D(V-H) ~ 0.1 mag. Assuming a solar metallicity, these values correspond to stellar ages of [?] 6 +- 3 Gyr. In contrast, the V-H color distribution of the exponential bulges peaks at [?]V-H ~ 0.9[?] and has a sigma D(V-H) ~ 0.4 mag. This likely implies significantly smaller ages and/or lower metallicities for (a significant fraction of the stars in) the exponential bulges compared to the R1/4-law spheroids. Most of the central nuclei hosted by the exponential bulges have V-H and J-H colors that are compatible with relatively unobscured stellar populations. Assuming no or little dust effects, ages [?]1 Gyr are suggested for these nuclei, which in turn imply masses of about a few 106 to a few 107 M, i.e., sufficient to dissolve progenitor bars with masses consistent with those inferred for the exponential bulges by their luminosities. While different bulge-nucleus pairs cover a large range of V-H colors, each bulge-nucleus pair has quite similar V-H colors and thus possibly similar stellar populations. The HST photometric analysis suggests that exponential-type bulge formation is taking place in the local universe and that this process is consistent with being the outcome of secular evolution processes within the disks. The structures that are currently formed inside the disks are quite dissimilar from the old elliptical-like spheroids that are hosted by the early-type disks.

AbstractMicroalbuminuria is associated with both an increased prevalence of cardiovascular risk factors and greater renal and cardiovascular morbidity. We questioned whether in the general population such associations can be found at lower levels of urinary albumin excretion than that of classically defined microalbuminuria. To that purpose urinary albumin concentration was measured in 40619 subjects aged 28 to 75 years. The subjects filled in a questionnaire on cardiovascular risk factors and events and were divided in deciles according to their urinary albumin concentration.Smoking was associated with albuminuria in the fifth or higher decile of urinary albumin concentration, that is with an albumin concentration of 5.1 mg/l and higher. The lower cut-off point for a positive association with hypertension was 8.8 mg/l, and for diabetes 11.2 mg/l. Family history for cardiovascular disease and hyperlipidaemia were not associated with albuminuria.We conclude that urinary albumin concentrations far below the microalbuminuric range are associated with increased prevalence of established cardiovascular risk factors. Family history for cardiovascular disease and hyperlipidaemia seems to behave differently. These data emphasize the need for more studies on the impact of albuminuria on the prediction of cardiovascular and renal disease in the general population.

Ischemic preconditioning has not only received wide attention in heart research, but has also been a topic of extensive studies involving other organs. In several of these studies, it has been shown that in spite of differences in the endpoints used to assess protection, the same mediators as in myocardial ischemic preconditioning may be involved. However, several of the putative mediators do not require ischemia to become activated. This has guided us and others to investigate whether the myocardium can also be protected by brief ischemia in other organs and whether other non-pharmacological forms of stress, which do not produce ischemia but are capable of activating these potential mediators, are also cardioprotective.