Call for a reference model of chronic hind limb ischemia to investigate therapeutic angiogenesis

A large number of studies utilize animal models to investigate therapeutic angiogenesis. However, the lack of a standardized experimental model leaves the comparison of different studies problematic. To establish a reference model of prolonged moderate tissue ischemia, we created unilateral hind limb ischemia in athymic rnu-rats by surgical excision of the femoral vessels. Blood flow of the limb was monitored for 60 days by laser Doppler imaging. Following a short postoperative period of substantially depressed perfusion, the animals showed a status of moderate hind limb ischemia from day 14 onwards. Thereafter, the perfusion remained at a constant level (55.5% of normal value) until the end of the observation period. Histopathological assessment of the ischemic musculature on postoperative days 28 and 60 showed essentially no inflammatory cell infiltrate or fibrosis. However, the mitochondrial activity and capillary-to-fiber ratio of the muscular tissue was reduced to 52.7% of normal, presenting with a significant weakness of the ischemic limb evidenced by a progressive decline in performance. Intramuscular injection of culture-expanded human endothelial progenitor cells (EPC) resulted in a significant increase in blood flow (82.0+/-3.5% of normal), capillary density (1.60+/-0.08/muscle fiber) and smooth muscle covered arterioles (8.0+/-0.6/high power field) in the ischemic hind limb as compared to controls (55.0+/-3.1%; 0.99+/-0.03; 5.0+/-0.2). In conclusion, chronic, moderate hind limb ischemia with consistently reduced perfusion levels persisting over a prolonged period can be established reliably in rnu athymic nude rats and is responsive to pro-angiogenic treatments such as EPC transplantation. This study provides a detailed protocol of a highly reproducible reference model to test novel therapeutic options for limb ischemia.

Impact of volcanic stratospheric aerosols on diurnal temperature range in Europe over the past 200 years: Observations versus model simulations

We analyze the impact of stratospheric volcanic aerosols on the diurnal temperature range (DTR) over Europe using long-term subdaily station records. We compare the results with a 28-member ensemble of European Centre/Hamburg version 5.4 (ECHAM5.4) general circulation model simulations. Eight stratospheric volcanic eruptions during the instrumental period are investigated. Seasonal all- and clear-sky DTR anomalies are compared with contemporary (approximately 20 year) reference periods. Clear sky is used to eliminate cloud effects and better estimate the signal from the direct radiative forcing of the volcanic aerosols. We do not find a consistent effect of stratospheric aerosols on all-sky DTR. For clear skies, we find average DTR anomalies of −0.08°C (−0.13°C) in the observations (in the model), with the largest effect in the second winter after the eruption. Although the clear-sky DTR anomalies from different stations, volcanic eruptions, and seasons show heterogeneous signals in terms of order of magnitude and sign, the significantly negative DTR anomalies (e.g., after the Tambora eruption) are qualitatively consistent with other studies. Referencing with clear-sky DTR anomalies to the radiative forcing from stratospheric volcanic eruptions, we find the resulting sensitivity to be of the same order of magnitude as previously published estimates for tropospheric aerosols during the so-called “global dimming” period (i.e., 1950s to 1980s). Analyzing cloud cover changes after volcanic eruptions reveals an increase in clear-sky days in both data sets. Quantifying the impact of stratospheric volcanic eruptions on clear-sky DTR over Europe provides valuable information for the study of the radiative effect of stratospheric aerosols and for geo-engineering purposes.

Indirectly measuring evaluations of several attitude objects in relation to a neutral reference point

This article presents a new response time measure of evaluations, the Evaluative Movement Assessment (EMA). Two properties are verified for the first time in a response time measure: (a) mapping of multiple attitude objects to a single scale, and (b) centering that scale around a neutral point. Property (a) has implications when self-report and response time measures of attitudes have a low correlation. A study using EMA as an indirect measure revealed a low correlation with self-reported attitudes when the correlation reflected between-subjects differences in preferences for one attitude object to a second. Previously this result may have been interpreted as dissociation between two measures. However, when correlations from the same data reflected within-subject preference rank orders between multiple attitude objects, they were substantial (average r = .64). This result suggests that the presence of low correlations between self-report and response time measures in previous studies may be a reflection of methodological aspects of the response time measurement techniques. Property (b) has implications for exploring theoretical questions that require assessment of whether an evaluation is positive or negative (e.g., prejudice), because it allows such classifications in response time measurement to be made for the first time.

Reference intervals for common carotid intima-media thickness measured with echotracking: relation with risk factors

AIMS Common carotid artery intima-media thickness (CCIMT) is widely used as a surrogate marker of atherosclerosis, given its predictive association with cardiovascular disease (CVD). The interpretation of CCIMT values has been hampered by the absence of reference values, however. We therefore aimed to establish reference intervals of CCIMT, obtained using the probably most accurate method at present (i.e. echotracking), to help interpretation of these measures. METHODS AND RESULTS We combined CCIMT data obtained by echotracking on 24 871 individuals (53% men; age range 15-101 years) from 24 research centres worldwide. Individuals without CVD, cardiovascular risk factors (CV-RFs), and BP-, lipid-, and/or glucose-lowering medication constituted a healthy sub-population (n = 4234) used to establish sex-specific equations for percentiles of CCIMT across age. With these equations, we generated CCIMT Z-scores in different reference sub-populations, thereby allowing for a standardized comparison between observed and predicted ('normal') values from individuals of the same age and sex. In the sub-population without CVD and treatment (n = 14 609), and in men and women, respectively, CCIMT Z-scores were independently associated with systolic blood pressure [standardized βs 0.19 (95% CI: 0.16-0.22) and 0.18 (0.15-0.21)], smoking [0.25 (0.19-0.31) and 0.11 (0.04-0.18)], diabetes [0.19 (0.05-0.33) and 0.19 (0.02-0.36)], total-to-HDL cholesterol ratio [0.07 (0.04-0.10) and 0.05 (0.02-0.09)], and body mass index [0.14 (0.12-0.17) and 0.07 (0.04-0.10)]. CONCLUSION We estimated age- and sex-specific percentiles of CCIMT in a healthy population and assessed the association of CV-RFs with CCIMT Z-scores, which enables comparison of IMT values for (patient) groups with different cardiovascular risk profiles, helping interpretation of such measures obtained both in research and clinical settings.

Draft Genome Sequence of the Virulent Clostridium chauvoei Reference Strain JF4335

Clostridium chauvoei is the etiological agent of blackleg, a disease of cattle and sheep with high mortality rates, causing severe economic losses in livestock production. Here, we report the draft genome sequence of the virulent C. chauvoei strain JF4335 (2.8 Mbp and 28% G+C content) and the annotation of the genome.

Impact of loading displacements on SLR-derived parameters and on the consistency between GNSS and SLR results

Displacements of the Earth’s surface caused by tidal and non-tidal loading forces are relevant in high-precision space geodesy. Some of the corrections are recommended by the international scientific community to be applied at the observation level, e.g., ocean tidal loading (OTL) and atmospheric tidal loading (ATL). Non-tidal displacement corrections are in general recommended not to be applied in the products of the International Earth Rotation and Reference Systems Service, in particular atmospheric non-tidal loading (ANTL), oceanic and hydrological non-tidal corrections. We assess and compare the impact of OTL, ATL and ANTL on SLR-derived parameters by reprocessing 12 years of SLR data considering and ignoring individual corrections. We show that loading displacements have an influence not only on station long-term stability, but also on geocenter coordinates, Earth Rotation Parameters, and satellite orbits. Applying the loading corrections reduces the amplitudes of annual signals in the time series of geocenter and station coordinates. The general improvement of the SLR station 3D coordinate repeatability when applying OTL, ATL and ANTL corrections are 19.5 %, 0.2 % and 3.3 % respectively, w.r.t. the solutions without loading corrections. ANTL corrections play a crucial role in the combination of optical (SLR) and microwave (GNSS, VLBI, DORIS) space geodetic observation techniques, because of the so-called Blue-Sky effect: SLR measurements can be carried out only under cloudless sky conditions—typically during high air pressure conditions, when the Earth’s crust is deformed, whereas microwave observations are weather-independent. Thus, applying the loading corrections at the observation level improves SLR-derived products as well as the consistency with microwave-based results. We assess the Blue-Sky effect on SLR stations and the consistency improvement between GNSS and SLR solutions when ANTL corrections are included. The omission of ANTL corrections may lead to inconsistencies between SLR and GNSS solutions of up to 2.5 mm for inland stations. As a result, the estimated GNSS–SLR coordinate differences correspond better to the local ties at the co-located stations when applying ANTL corrections.

SLR-derived terrestrial reference frame using the observations to LAGEOS-1/2, Starlette, Stella, and AJISAI

Currently, the contributions of Starlette, Stella, and AJISAI are not taken into account when defining the International Terrestrial Reference Frame (ITRF), despite the large amount of data collected in a long time-span. Consequently, the SLR-derived parameters and the SLR part of the ITRF are almost exclusively defined by LAGEOS-1 and LAGEOS-2. We investigate the potential of combining the observations to several SLR satellites with different orbital characteristics. Ten years of SLR data are homogeneously processed using the development version 5.3 of the Bernese GNSS Software. Special emphasis is put on orbit parameterization and the impact of LEO data on the estimation of the geocenter coordinates, Earth rotation parameters, Earth gravity field coefficients, and the station coordinates in one common adjustment procedure. We find that the parameters derived from the multi-satellite solutions are of better quality than those obtained in single satellite solutions or solutions based on the two LAGEOS satellites. A spectral analysis of the SLR network scale w.r.t. SLRF2008 shows that artifacts related to orbit perturbations in the LAGEOS-1/2 solutions, i.e., periods related to the draconitic years of the LAGEOS satellites, are greatly reduced in the combined solutions.

A robust reference signal generator for synchronized ventricular assist devices

Ventricular assist devices (VADs) are blood pumps that offer an option to support the circulation of patients with severe heart failure. Since a failing heart has a remaining pump function, its interaction with the VAD influences the hemodynamics. Ideally, the heart's action is taken into account for actuating the device such that the device is synchronized to the natural cardiac cycle. To realize this in practice, a reliable real-time algorithm for the automatic synchronization of the VAD to the heart rate is required. This paper defines the tasks such an algorithm needs to fulfill: the automatic detection of irregular heart beats and the feedback control of the phase shift between the systolic phases of the heart and the assist device. We demonstrate a possible solution to these problems and analyze its performance in two steps. First, the algorithm is tested using the MIT-BIH arrhythmia database. Second, the algorithm is implemented in a controller for a pulsatile and a continuous-flow VAD. These devices are connected to a hybrid mock circulation where three test scenarios are evaluated. The proposed algorithm ensures a reliable synchronization of the VAD to the heart cycle, while being insensitive to irregularities in the heart rate.