Coronary collateral perfusion in patients with coronary artery disease: effect of metoprolol

BACKGROUND The use of ultrathin Doppler angioplasty guidewires has made it possible to measure collateral flow quantitatively. Pharmacologic interventions have been shown to influence collateral flow and, thus, to affect myocardial ischaemia. METHODS Twenty-five patients with coronary artery disease undergoing PTCA were included in the present analysis. Coronary flow velocities were measured in the ipsilateral (n = 25) and contralateral (n = 6; two Doppler wires) vessels during PTCA with and without i.v. adenosine (140 microg/kg.min) before and 3 min after 5 mg metoprolol i.v., respectively. The ipsilateral Doppler wire was positioned distal to the stenosis, whereas the distal end of the contralateral wire was in an angiographically normal vessel. The flow signals of the ipsilateral wire were used to calculate the collateral flow index (CFI). CFI was defined as the ratio of flow velocity during balloon inflation divided by resting flow. RESULTS Heart rate and mean aortic pressure decreased slightly (ns) after i.v. metoprolol. The collateral flow index was 0.25+/-0.12 (one fourth of the resting coronary flow) during the first PTCA and 0.27+/-0.14 (ns versus first PTCA) during the second PTCA, but decreased with metoprolol to 0.16+/-0.08 (p<0.0001 vs. baseline) during the third PTCA. CONCLUSIONS Coronary collateral flow increased slightly but not significantly during maximal vasodilatation with adenosine but decreased in 23 of 25 patients after i.v. metoprolol. Thus, there is a reduction in coronary collateral flow with metoprolol, probably due to an increase in coronary collateral resistance or a reduction in oxygen demand.

Cichlid species-area relationships are shaped by adaptive radiations that scale with area

A positive relationship between species richness and island size is thought to emerge from an equilibrium between immigration and extinction rates, but the influence of species diversification on the form of this relationship is poorly understood. Here, we show that within-lake adaptive radiation strongly modifies the species-area relationship for African cichlid fishes. The total number of species derived from in situ speciation increases with lake size, resulting in faunas orders of magnitude higher in species richness than faunas assembled by immigration alone. Multivariate models provide evidence for added influence of lake depth on the species-area relationship. Diversity of clades representing within-lake radiations show responses to lake area, depth and energy consistent with limitation by these factors, suggesting that ecological factors influence the species richness of radiating clades within these ecosystems. Together, these processes produce lake fish faunas with highly variable composition, but with diversities that are well predicted by environmental variables.

Portal vein omentin is increased in patients with liver cirrhosis but is not associated with complications of portal hypertension

BACKGROUND: Omentin is a visceral fat-derived adipokine associated with endothelium-dependent vasodilation. Impaired endothelial function is a major cause of portal hypertension in liver cirrhosis. The aim was to assess associations of omentin with systemic markers of endothelial function, namely arginine and asymmetric dimethylarginine (ADMA) and complications of portal hypertension in liver cirrhosis. MATERIALS AND METHODS: Systemic omentin was measured by ELISA in portal venous serum (PVS), systemic venous serum (SVS) and hepatic venous serum (HVS) of 40 patients with liver cirrhosis and 10 liver-healthy controls. ADMA and arginine were determined in SVS of the patients by ELISA. RESULTS: Omentin is elevated in PVS and tends to be increased in SVS and HVS of patients with liver cirrhosis compared with controls. Omentin is principally expressed in visceral fat, and PVS omentin tends to be higher than SVS levels. Lower HVS than PVS omentin suggests that omentin may be partly removed from the circulation by the liver. Omentin in serum is not associated with stages of liver cirrhosis defined by CHILD-POUGH or MELD score and is not affected in patients with ascites. HVS omentin tends to be reduced in patients with large varices compared with patients without/with small varices. Arginine/ADMA ratio is reduced in patients with massive ascites but is not associated with variceal size. Further, Arginine/ADMA ratio does not correlate with omentin. CONCLUSION: Current data show that PVS omentin is increased in liver cirrhosis but is not associated with complications of portal hypertension

Search for single b*-quark production with the ATLAS detector at sqrts=7 TeV

The results of a search for an excited bottom-quark b* in pp collisions at root s = 7 TeV, using 4.7 fb(-1) of data collected by the ATLAS detector at the LHC are presented. In the model studied, a single b*-quark is produced through a chromomagnetic interaction and subsequently decays to a W boson and a top quark. The search is performed in the dilepton and lepton + jets final states, which are combined to set limits on b*-quark couplings for a range of b*-quark masses. For a benchmark with unit size chromomagnetic and Standard Model-like electroweak b* couplings, b* quarks with masses less than 870 GeV are excluded at the 95% credibility level.

Prognostic factors and risk groups in T1G3 non-muscle-invasive bladder cancer patients initially treated with Bacillus Calmette-Guérin: results of a retrospective multicenter study of 2451 patients

BACKGROUND The impact of prognostic factors in T1G3 non-muscle-invasive bladder cancer (BCa) patients is critical for proper treatment decision making. OBJECTIVE To assess prognostic factors in patients who received bacillus Calmette-Guérin (BCG) as initial intravesical treatment of T1G3 tumors and to identify a subgroup of high-risk patients who should be considered for more aggressive treatment. DESIGN, SETTING, AND PARTICIPANTS Individual patient data were collected for 2451 T1G3 patients from 23 centers who received BCG between 1990 and 2011. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Using Cox multivariable regression, the prognostic importance of several clinical variables was assessed for time to recurrence, progression, BCa-specific survival, and overall survival (OS). RESULTS AND LIMITATIONS With a median follow-up of 5.2 yr, 465 patients (19%) progressed, 509 (21%) underwent cystectomy, and 221 (9%) died because of BCa. In multivariable analyses, the most important prognostic factors for progression were age, tumor size, and concomitant carcinoma in situ (CIS); the most important prognostic factors for BCa-specific survival and OS were age and tumor size. Patients were divided into four risk groups for progression according to the number of adverse factors among age ≥ 70 yr, size ≥ 3 cm, and presence of CIS. Progression rates at 10 yr ranged from 17% to 52%. BCa-specific death rates at 10 yr were 32% in patients ≥ 70 yr with tumor size ≥ 3 cm and 13% otherwise. CONCLUSIONS T1G3 patients ≥ 70 yr with tumors ≥ 3 cm and concomitant CIS should be treated more aggressively because of the high risk of progression. PATIENT SUMMARY Although the majority of T1G3 patients can be safely treated with intravesical bacillus Calmette-Guérin, there is a subgroup of T1G3 patients with age ≥ 70 yr, tumor size ≥ 3 cm, and concomitant CIS who have a high risk of progression and thus require aggressive treatment.

An adaptive Newton-method based on a dynamical systems approach

The traditional Newton method for solving nonlinear operator equations in Banach spaces is discussed within the context of the continuous Newton method. This setting makes it possible to interpret the Newton method as a discrete dynamical system and thereby to cast it in the framework of an adaptive step size control procedure. In so doing, our goal is to reduce the chaotic behavior of the original method without losing its quadratic convergence property close to the roots. The performance of the modified scheme is illustrated with various examples from algebraic and differential equations.

Larger visual stimuli are perceived to last longer from time to time: The internal clock is not affected by nontemporal visual stimulus size

Performance on interval timing is often explained by the assumption of an internal clock based on neural counting. According to this account, a neural pacemaker generates pulses, and the number of pulses relating to a physical time interval is recorded by a counter. Thus, the number of accumulated pulses is the internal representation of this interval. Several studies demonstrated that large visual stimuli are perceived to last longer than smaller ones presented for the same duration. The present study was designed to investigate whether nontemporal visual stimulus size directly affects the internal clock. For this purpose, a temporal reproduction task was applied. Sixty participants were randomly assigned to one of two experimental conditions with stimulus size being experimentally varied within either the target or the reproduction interval. A direct effect of nontemporal stimulus size on the pacemaker-counter system should become evident irrespective of whether stimulus size was experimentally varied within the target or the reproduction interval. An effect of nontemporal stimulus size on reproduced duration only occurred when stimulus size was varied during the target interval. This finding clearly argues against the notion that nontemporal visual stimulus size directly affects the internal clock. Furthermore, our findings ruled out a decisional bias as a possible cause of the observed differential effect of stimulus size on reproduced duration. Rather the effect of stimulus size appeared to originate from the memory stage of temporal information processing at which the timing signal from the pacemaker-counter component is encoded in reference memory.

Reduced serum chemerin in patients with more severe liver cirrhosis

Chemerin is a well-established modulator of immune cell function and its serum levels are induced in inflammatory diseases. Liver cirrhosis is associated with inflammation which is aggravated by portal hypertension. The objective of this study was to evaluate whether chemerin is induced in patients with more severe liver cirrhosis and portal hypertension. Chemerin has been measured by ELISA in the portal venous serum (PVS), systemic venous serum (SVS) and hepatic venous serum (HVS) of 45 patients with liver cirrhosis. Chemerin is higher in HVS compared to PVS in accordance with our recently published finding. SVS, HVS and PVS chemerin decline in patients with more advanced liver injury defined by the CHILD-PUGH score. Hepatic chemerin has been determined in a small cohort and is similarly expressed in normal and cirrhotic liver. MELD score and serum markers of liver and kidney function do not correlate with chemerin. There is a positive correlation of chemerin in all compartments with Quick prothrombin time and of SVS chemerin with systolic blood pressure. PVS chemerin is induced in patients with modest/massive ascites but this does not translate into higher HVS and SVS levels. Chemerin is not associated with variceal size. Reduction of portal pressure by transjugular intrahepatic portosystemic shunt does not affect chemerin levels. These data show that low chemerin in patients with more severe liver cirrhosis is associated with reduced Quick prothrombin time.

Urinary tract endometriosis in patients with deep infiltrating endometriosis: prevalence, symptoms, management, and proposal for a new clinical classification

OBJECTIVE To analyze the prevalence of urinary tract endometriosis (UTE) in patients with deep infiltrating endometriosis (DIE) and to define potential criteria for preoperative workup. DESIGN Retrospective study. SETTING University hospital. PATIENT(S) Six hundred ninety-seven patients with endometriosis. INTERVENTION(S) Excision of all endometriotic lesions. MAIN OUTCOME MEASURE(S) Correlation of preoperative features and intraoperative findings in patients with UTE. RESULT(S) Out of 213 patients presenting DIE, 52.6% suffered from UTE. In patients with ureteral endometriosis, symptoms were not specific. Among the patients with bladder endometriosis, 68.8% complained of urinary symptoms compared to 7.9% in the group of patients without UTE. In patients with rectovaginal endometriosis, the probability of ureterolysis showed a linear correlation with the size of the nodule. We found that 3 cm in diameter provided a specific cutoff value for the likelihood of ureteric involvement. CONCLUSION(S) The prevalence of UTE has often been underestimated. Preoperative questioning is important in the search for bladder endometriosis. The size of the nodule is one of the few reliable criteria in preoperative assessment that can suggest ureteric involvement. We propose a classification of ureteral endometriosis that will allow the standardization of terminology and help to compare the outcome of different surgical treatment in randomized studies.

Dissolution-Precipitation in Porous Media: Experiments and Modelling

The evolution of porosity due to dissolution/precipitation processes of minerals and the associated change of transport parameters are of major interest for natural geological environments and engineered underground structures. We designed a reproducible and fast to conduct 2D experiment, which is flexible enough to investigate several process couplings implemented in the numerical code OpenGeosys-GEM (OGS-GEM). We investigated advective-diffusive transport of solutes, effect of liquid phase density on advective transport, and kinetically controlled dissolution/precipitation reactions causing porosity changes. In addition, the system allowed to investigate the influence of microscopic (pore scale) processes on macroscopic (continuum scale) transport. A Plexiglas tank of dimension 10 × 10 cm was filled with a 1 cm thick reactive layer consisting of a bimodal grain size distribution of celestite (SrSO4) crystals, sandwiched between two layers of sand. A barium chloride solution was injected into the tank causing an asymmetric flow field to develop. As the barium chloride reached the celestite region, dissolution of celestite was initiated and barite precipitated. Due to the higher molar volume of barite, its precipitation caused a porosity decrease and thus also a decrease in the permeability of the porous medium. The change of flow in space and time was observed via injection of conservative tracers and analysis of effluents. In addition, an extensive post-mortem analysis of the reacted medium was conducted. We could successfully model the flow (with and without fluid density effects) and the transport of conservative tracers with a (continuum scale) reactive transport model. The prediction of the reactive experiments initially failed. Only the inclusion of information from post-mortem analysis gave a satisfactory match for the case where the flow field changed due to dissolution/precipitation reactions. We concentrated on the refinement of post-mortem analysis and the investigation of the dissolution/precipitation mechanisms at the pore scale. Our analytical techniques combined scanning electron microscopy (SEM) and synchrotron X-ray micro-diffraction/micro-fluorescence performed at the XAS beamline (Swiss Light Source). The newly formed phases include an epitaxial growth of barite micro-crystals on large celestite crystals (epitaxial growth) and a nano-crystalline barite phase (resulting from the dissolution of small celestite crystals) with residues of celestite crystals in the pore interstices. Classical nucleation theory, using well-established and estimated parameters describing barite precipitation, was applied to explain the mineralogical changes occurring in our system. Our pore scale investigation showed limits of the continuum scale reactive transport model. Although kinetic effects were implemented by fixing two distinct rates for the dissolution of large and small celestite crystals, instantaneous precipitation of barite was assumed as soon as oversaturation occurred. Precipitation kinetics, passivation of large celestite crystals and metastability of supersaturated solutions, i.e. the conditions under which nucleation cannot occur despite high supersaturation, were neglected. These results will be used to develop a pore scale model that describes precipitation and dissolution of crystals at the pore scale for various transport and chemical conditions. Pore scale modelling can be used to parameterize constitutive equations to introduce pore-scale corrections into macroscopic (continuum) reactive transport models. Microscopic understanding of the system is fundamental for modelling from the pore to the continuum scale.

Two distinct filopodia populations at the growth cone allow to sense nanotopographical extracellular matrix cues to guide neurite outgrowth

BACKGROUND The process of neurite outgrowth is the initial step in producing the neuronal processes that wire the brain. Current models about neurite outgrowth have been derived from classic two-dimensional (2D) cell culture systems, which do not recapitulate the topographical cues that are present in the extracellular matrix (ECM) in vivo. Here, we explore how ECM nanotopography influences neurite outgrowth. METHODOLOGY/PRINCIPAL FINDINGS We show that, when the ECM protein laminin is presented on a line pattern with nanometric size features, it leads to orientation of neurite outgrowth along the line pattern. This is also coupled with a robust increase in neurite length. The sensing mechanism that allows neurite orientation occurs through a highly stereotypical growth cone behavior involving two filopodia populations. Non-aligned filopodia on the distal part of the growth cone scan the pattern in a lateral back and forth motion and are highly unstable. Filopodia at the growth cone tip align with the line substrate, are stabilized by an F-actin rich cytoskeleton and enable steady neurite extension. This stabilization event most likely occurs by integration of signals emanating from non-aligned and aligned filopodia which sense different extent of adhesion surface on the line pattern. In contrast, on the 2D substrate only unstable filopodia are observed at the growth cone, leading to frequent neurite collapse events and less efficient outgrowth. CONCLUSIONS/SIGNIFICANCE We propose that a constant crosstalk between both filopodia populations allows stochastic sensing of nanotopographical ECM cues, leading to oriented and steady neurite outgrowth. Our work provides insight in how neuronal growth cones can sense geometric ECM cues. This has not been accessible previously using routine 2D culture systems.

A SIMULATION STUDY OF THE SIZE AND POWER OF SOME TWO-SAMPLE TESTS FOR UNEQUALLY CENSORED SURVIVAL DATA (RANK TESTS, LOGRANK, PROPORTIONAL HAZARDS, WILCOXON TESTS, EXPONENTIAL DISTRIBUTION)

Sizes and power of selected two-sample tests of the equality of survival distributions are compared by simulation for small samples from unequally, randomly-censored exponential distributions. The tests investigated include parametric tests (F, Score, Likelihood, Asymptotic), logrank tests (Mantel, Peto-Peto), and Wilcoxon-Type tests (Gehan, Prentice). Equal sized samples, n = 18, 16, 32 with 1000 (size) and 500 (power) simulation trials, are compared for 16 combinations of the censoring proportions 0%, 20%, 40%, and 60%. For n = 8 and 16, the Asymptotic, Peto-Peto, and Wilcoxon tests perform at nominal 5% size expectations, but the F, Score and Mantel tests exceeded 5% size confidence limits for 1/3 of the censoring combinations. For n = 32, all tests showed proper size, with the Peto-Peto test most conservative in the presence of unequal censoring. Powers of all tests are compared for exponential hazard ratios of 1.4 and 2.0. There is little difference in power characteristics of the tests within the classes of tests considered. The Mantel test showed 90% to 95% power efficiency relative to parametric tests. Wilcoxon-type tests have the lowest relative power but are robust to differential censoring patterns. A modified Peto-Peto test shows power comparable to the Mantel test. For n = 32, a specific Weibull-exponential comparison of crossing survival curves suggests that the relative powers of logrank and Wilcoxon-type tests are dependent on the scale parameter of the Weibull distribution. Wilcoxon-type tests appear more powerful than logrank tests in the case of late-crossing and less powerful for early-crossing survival curves. Guidelines for the appropriate selection of two-sample tests are given. ^

Dive depth and dive duration data of subadult and adult, male and female southern elephant seals from Marion Island between 2004 and 2008 with links to datasets

Sexual segregation in habitat use occurs in a number of animal species, including southern elephant seals, where differences in migration localities and dive behaviour between sexes have been recorded. Due to the extreme sexual size dimorphism exhibited by southern elephant seals, it is unclear whether observed differences in dive behaviour are due to increased physiological capacity of males, compared to females, or differences in activity budgets and foraging behaviour. Here we use a mixed-effects modelling approach to investigate the effects of sex, size, age and individual variation on a number of dive parameters measured on southern elephant seals from Marion Island. Although individual variation accounted for substantial portions of total model variance for many response variables, differences in maximum and targeted dive depths were always influenced by sex, and only partly by body length. Conversely, dive durations were always influenced by body length, while sex was not identified as a significant influence. These results support hypotheses that physiological capability associated with body size is a limiting factor on dive durations. However, differences in vertical depth use appear to be the result of differences in forage selection between sexes, rather than a by-product of the size dimorphism displayed by this species. This provides further support for resource partitioning and possible avoidance of inter-sexual competition in southern elephant seals.

Biomass and stable isotope composition of plankton in five size fractions along a zonal transect (24°N) from the Canary Islands to Florida in January-March 2011

The spatial variability of biomass and stable isotopes in plankton size fractions in the upper 200 m was studied in a high spatial resolution transect along 24°N from Canary Islands to Florida (January - March 2011) during Leg 8 of the Malaspina-2010 expedition (http://www.expedicionmalaspina.es) to determine nitrogen and carbon sources. Plankton samples were collected by vertical tows of a microplankton net (40 mm mesh size) and a mesoplankton net (200 mm mesh size) through the upper 200 m of the water column. Sampling was between 10:00 and 16:00 h GMT. Plankton was separated into five size fractions (40 - 200, 200 - 500, 500 - 1000, 1000 - 2000 and > 2000 mm) by gentle filtration of the samples by a graded series of nylon sieves (2000, 1000, 500, 200 and 40 mm). Large gelatinous organisms were removed before filtration. Aliquots for each size fraction were collected on pre-weighed glass-fibre filters, dried (60°C, 48 h) and stored in a desiccator before determination of biomass (dry weight), carbon and nitrogen content and natural abundance of stable carbon and nitrogen isotopes ashore. Vertical advection of waters predominated in lateral zones while the central Atlantic (30-70°W) was characterized by a strong stratification and oligotrophic surface waters. Plankton biomass was low in the central zone and high in both eastern and western sides, with most of the variability due to either large (>2000 µm) and small plankton (<500 µm). Carbon isotopes reflected mainly the advection the deep water in lateral zones. Stable nitrogen isotopes showed a nearly symmetrical spatial distribution in all fractions, with the lowest values (delta15N <1per mill) in the central zone, and were inversely correlated to carbon stable isotopes (delta13C) and to the abundance of the nitrogen-fixer Trichodesmium. Diazotrophy was estimated to account for >50% of organic nitrogen in the central zone, and even >30% in eastern and western zones. The impact of diazotrophy increased with the size of the organisms, supporting the wide participation of all trophic levels in the processing of recently fixed nitrogen. These results indicate that atmospheric sources of carbon and nitrogen prevail over deep water sources in the subtropical North Atlantic and that the zone influenced by diazotrophy is much larger than reported in previous studies.

Heat flow ratios of stations from the Iberian abyssal plain (Table 1)

New heat flow observations have been made in the Iberia abyssal plain off the Galicia margin along the transeat of Ocean Drilling Program Leg 149 drill sites. in order to investigate the nature of this unusually wide and deep continet-ocean transition region. Our results indicate the presence of three separate zones. Average values of 47.5 +/- 3 mW/m in the westernmost zone III agree with predictions of standard oceanic lithospheric models for its estimated age of 126 Ma. In contrast, the heat flow within zone II is 5-15 mW/m higher than predicted. assuming that the mantle heat flow remains constant across the basin. This region of high values is coincident with the location of a major intra-crustal "S"-type reflector east of ODP Site 900. and the anomaly is consistent with the presence of 2-3 km of primarily upper continental crust above the reflector, with concentrations of radiogenic components similar to those from granodiorite samplles dredged off Galicia Bank. It is not, however, consistent with the low values of heat production measured on gabbroic sanhples from its western end at ODP Site 900. In zone I, detailed measurements across the tilted fault block south of ODP Site 901 show consistent variations which closely match predictions due to the effects of basement structure and sediment deposition. There is no evidence for variations due to vertical convective transport along the dipping basement fault block. Once corrected for these variations. measurements in zone I yield average values that agree quite well with previous measurements across Calicia Bank. indicating no systematic landward increase in heat flow with decreasing amounts of continental, extension.