Progenitor cell recruitment during individualized high-flow, very-large-volume apheresis for autologous transplantation improves collection efficiency

BACKGROUND: Individual adaptation of processed patient's blood volume (PBV) should reduce number and/or duration of autologous peripheral blood progenitor cell (PBPC) collections. STUDY DESIGN AND METHODS: The durations of leukapheresis procedures were adapted by means of an interim analysis of harvested CD34+ cells to obtain the intended yield of CD34+ within as few and/or short as possible leukapheresis procedures. Absolute efficiency (AE; CD34+/kg body weight) and relative efficiency (RE; total CD34+ yield of single apheresis/total number of preapheresis CD34+) were calculated, assuming an intraapheresis recruitment if RE was greater than 1, and a yield prediction models for adults was generated. RESULTS: A total of 196 adults required a total of 266 PBPC collections. The median AE was 7.99 x 10(6), and the median RE was 1.76. The prediction model for AE showed a satisfactory predictive value for preapheresis CD34+ only. The prediction model for RE also showed a low predictive value (R2 = 0.36). Twenty-eight children underwent 44 PBPC collections. The median AE was 12.13 x 10(6), and the median RE was 1.62. Major complications comprised bleeding episodes related to central venous catheters (n = 4) and severe thrombocytopenia of less than 10 x 10(9) per L (n = 16). CONCLUSION: A CD34+ interim analysis is a suitable tool for individual adaptation of the duration of leukapheresis. During leukapheresis, a substantial recruitment of CD34+ was observed, resulting in a RE of greater than 1 in more than 75 percent of patients. The upper limit of processed PBV showing an intraapheresis CD34+ recruitment is higher than in a standard large-volume leukapheresis. Therefore, a reduction of individually needed PBPC collections by means of a further escalation of the processed PBV seems possible.

Can decision making in general surgery be based on evidence? An empirical study of Cochrane Reviews

BACKGROUND: This empirical study analyzes the current status of Cochrane Reviews (CRs) and their strength of recommendation for evidence-based decision making in the field of general surgery. METHODS: Systematic literature search of the Cochrane Database of Systematic Reviews and the Cochrane Collaboration's homepage to identify available CRs on surgical topics. Quantitative and qualitative characteristics, utilization, and formulated treatment recommendations were evaluated by 2 independent reviewers. Association of review characteristics with treatment recommendation was analyzed using univariate and multivariate logistic regression models. RESULTS: Ninety-three CRs, including 1,403 primary studies and 246,473 patients, were identified. Mean number of included primary studies per CR was 15.1 (standard deviation [SD] 14.5) including 2,650 (SD 3,340) study patients. Two and a half (SD 8.3) nonrandomized trials were included per analyzed CR. Seventy-two (77%) CRs were published or updated in 2005 or later. Explicit treatment recommendations were given in 45 (48%). Presence of a treatment recommendation was associated with the number of included primary studies and the proportion of randomized studies. Utilization of surgical CRs remained low and showed large inter-country differences. The most surgical CRs were accessed in UK, USA, and Australia, followed by several Western and Eastern European countries. CONCLUSION: Only a minority of available CRs address surgical questions and their current usage is low. Instead of unsystematically increasing the number of surgical CRs it would be far more efficient to focus the review process on relevant surgical questions. Prioritization of CRs needs valid methods which should be developed by the scientific surgical community.

Multimeric tyrosine sulfate acts as an endothelial cell protectant and prevents complement activation in xenotransplantation models

BACKGROUND: Activation of endothelial cells (EC) in xenotransplantation is mostly induced through binding of antibodies (Ab) and activation of the complement system. Activated EC lose their heparan sulfate proteoglycan (HSPG) layer and exhibit a procoagulant and pro-inflammatory cell surface. We have recently shown that the semi-synthetic proteoglycan analog dextran sulfate (DXS, MW 5000) blocks activation of the complement cascade and acts as an EC-protectant both in vitro and in vivo. However, DXS is a strong anticoagulant and systemic use of this substance in a clinical setting might therefore be compromised. It was the aim of this study to investigate a novel, fully synthetic EC-protectant with reduced inhibition of the coagulation system. METHOD: By screening with standard complement (CH50) and coagulation assays (activated partial thromboplastin time, aPTT), a conjugate of tyrosine sulfate to a polymer-backbone (sTyr-PAA) was identified as a candidate EC-protectant. The pathway-specificity of complement inhibition by sTyr-PAA was tested in hemolytic assays. To further characterize the substance, the effects of sTyr-PAA and DXS on complement deposition on pig cells were compared by flow cytometry and cytotoxicity assays. Using fluorescein-labeled sTyr-PAA (sTyr-PAA-Fluo), the binding of sTyr-PAA to cell surfaces was also investigated. RESULTS: Of all tested compounds, sTyr-PAA was the most effective substance in inhibiting all three pathways of complement activation. Its capacity to inhibit the coagulation cascade was significantly reduced as compared with DXS. sTyr-PAA also dose-dependently inhibited deposition of human complement on pig cells and this inhibition correlated with the binding of sTyr-PAA to the cells. Moreover, we were able to demonstrate that sTyr-PAA binds preferentially and dose-dependently to damaged EC. CONCLUSIONS: We could show that sTyr-PAA acts as an EC-protectant by binding to the cells and protecting them from complement-mediated damage. It has less effect on the coagulation system than DXS and may therefore have potential for in vivo application.

Flow-Centric, Back-In-Time Debugging

Conventional debugging tools present developers with means to explore the run-time context in which an error has occurred. In many cases this is enough to help the developer discover the faulty source code and correct it. However, rather often errors occur due to code that has executed in the past, leaving certain objects in an inconsistent state. The actual run-time error only occurs when these inconsistent objects are used later in the program. So-called back-in-time debuggers help developers step back through earlier states of the program and explore execution contexts not available to conventional debuggers. Nevertheless, even back-in-time debuggers do not help answer the question, ``Where did this object come from?'' The Object-Flow Virtual Machine, which we have proposed in previous work, tracks the flow of objects to answer precisely such questions, but this VM does not provide dedicated debugging support to explore faulty programs. In this paper we present a novel debugger, called Compass, to navigate between conventional run-time stack-oriented control flow views and object flows. Compass enables a developer to effectively navigate from an object contributing to an error back-in-time through all the code that has touched the object. We present the design and implementation of Compass, and we demonstrate how flow-centric, back-in-time debugging can be used to effectively locate the source of hard-to-find bugs.

Flow-R, a model for susceptibility mapping of debris flows and other gravitational hazards at a regional scale

The development of susceptibility maps for debris flows is of primary importance due to population pressure in hazardous zones. However, hazard assessment by process-based modelling at a regional scale is difficult due to the complex nature of the phenomenon, the variability of local controlling factors, and the uncertainty in modelling parameters. A regional assessment must consider a simplified approach that is not highly parameter dependant and that can provide zonation with minimum data requirements. A distributed empirical model has thus been developed for regional susceptibility assessments using essentially a digital elevation model (DEM). The model is called Flow-R for Flow path assessment of gravitational hazards at a Regional scale (available free of charge under http://www.flow-r.org) and has been successfully applied to different case studies in various countries with variable data quality. It provides a substantial basis for a preliminary susceptibility assessment at a regional scale. The model was also found relevant to assess other natural hazards such as rockfall, snow avalanches and floods. The model allows for automatic source area delineation, given user criteria, and for the assessment of the propagation extent based on various spreading algorithms and simple frictional laws. We developed a new spreading algorithm, an improved version of Holmgren's direction algorithm, that is less sensitive to small variations of the DEM and that is avoiding over-channelization, and so produces more realistic extents. The choices of the datasets and the algorithms are open to the user, which makes it compliant for various applications and dataset availability. Amongst the possible datasets, the DEM is the only one that is really needed for both the source area delineation and the propagation assessment; its quality is of major importance for the results accuracy. We consider a 10 m DEM resolution as a good compromise between processing time and quality of results. However, valuable results have still been obtained on the basis of lower quality DEMs with 25 m resolution.

Proton entry into the near-lunar plasma wake for magnetic field aligned flow

We report the first observation of protons in the near-lunar (100-200 km from the surface) and deeper (near anti-subsolar point) plasma wake when the interplanetary magnetic field (IMF) and solar wind velocity (vsw) are parallel (aligned flow; angle between IMF and vsw≤10°). More than 98% of the observations during aligned flow condition showed the presence of protons in the wake. These observations are obtained by the Solar Wind Monitor sensor of the Sub-keV Atom Reflecting Analyser experiment on Chandrayaan-1. The observation cannot be explained by the conventional fluid models for aligned flow. Back tracing of the observed protons suggests that their source is the solar wind. The larger gyroradii of the wake protons compared to that of solar wind suggest that they were part of the tail of the solar wind velocity distribution function. Such protons could enter the wake due to their large gyroradii even when the flow is aligned to IMF. However, the wake boundary electric field may also play a role in the entry of the protons into the wake.

Prospective memory, executive functions and metacognitive control: An empirical approach to their structural interrelations in young elementary school children

Introduction Prospective memory (PM), the ability to remember to perform intended activities in the future (Kliegel & Jäger, 2007), is crucial to succeed in everyday life. PM seems to improve gradually over the childhood years (Zimmermann & Meier, 2006), but yet little is known about PM competences in young school children in general, and even less is known about factors influencing its development. Currently, a number of studies suggest that executive functions (EF) are potentially influencing processes (Ford, Driscoll, Shum & Macaulay, 2012; Mahy & Moses, 2011). Additionally, metacognitive processes (MC: monitoring and control) are assumed to be involved while optimizing one’s performance (Krebs & Roebers, 2010; 2012; Roebers, Schmid, & Roderer, 2009). Yet, the relations between PM, EF and MC remain relatively unspecified. We intend to empirically examine the structural relations between these constructs. Method A cross-sectional study including 119 2nd graders (mage = 95.03, sdage = 4.82) will be presented. Participants (n = 68 girls) completed three EF tasks (stroop, updating, shifting), a computerised event-based PM task and a MC spelling task. The latent variables PM, EF and MC that were represented by manifest variables deriving from the conducted tasks, were interrelated by structural equation modelling. Results Analyses revealed clear associations between the three cognitive constructs PM, EF and MC (rpm-EF = .45, rpm-MC = .23, ref-MC = .20). A three factor model, as opposed to one or two factor models, appeared to fit excellently to the data (chi2(17, 119) = 18.86, p = .34, remsea = .030, cfi = .990, tli = .978). Discussion The results indicate that already in young elementary school children, PM, EF and MC are empirically well distinguishable, but nevertheless substantially interrelated. PM and EF seem to share a substantial amount of variance while for MC, more unique processes may be assumed.

Endothelial function and sleep: associations of flow-mediated dilation with perceived sleep quality and rapid eye movement (REM) sleep.

Endothelial function typically precedes clinical manifestations of cardiovascular disease and provides a potential mechanism for the associations observed between cardiovascular disease and sleep quality. This study examined how subjective and objective indicators of sleep quality relate to endothelial function, as measured by brachial artery flow-mediated dilation (FMD). In a clinical research centre, 100 non-shift working adults (mean age: 36 years) completed FMD testing and the Pittsburgh Sleep Quality Index, along with a polysomnography assessment to obtain the following measures: slow wave sleep, percentage rapid eye movement (REM) sleep, REM sleep latency, total arousal index, total sleep time, wake after sleep onset, sleep efficiency and apnea-hypopnea index. Bivariate correlations and follow-up multiple regressions examined how FMD related to subjective (i.e., Pittsburgh Sleep Quality Index scores) and objective (i.e., polysomnography-derived) indicators of sleep quality. After FMD showed bivariate correlations with Pittsburgh Sleep Quality Index scores, percentage REM sleep and REM latency, further examination with separate regression models indicated that these associations remained significant after adjustments for sex, age, race, hypertension, body mass index, apnea-hypopnea index, smoking and income (Ps < 0.05). Specifically, as FMD decreased, scores on the Pittsburgh Sleep Quality Index increased (indicating decreased subjective sleep quality) and percentage REM sleep decreased, while REM sleep latency increased (Ps < 0.05). Poorer subjective sleep quality and adverse changes in REM sleep were associated with diminished vasodilation, which could link sleep disturbances to cardiovascular disease.

Vertical integration and information sharing — an empirical investigation in the German apparel industry

Despite the astounding success of the fast fashion retailers, the management practices leading to these results have not been subject to extensive research so far. Given this background, we analyze the impact of information sharing and vertical integration on the performance of 51 German apparel companies. We find that the positive impact of vertical integration is mediated by information sharing, i.e. that the ability to improve the information flow is a key success factor of vertically integrated apparel supply chains. Thus, the success of an expansion strategy based on vertical integration critically depends on effective ways to share logistical information.

Combined effects of heterogeneity, anisotropy, and saturation on steady state flow and transport: A laboratory sand tank experiment

Field soils show rather different spreading behavior at different water saturations, frequently caused by layering of the soil material. We performed tracer experiments in a laboratory sand tank. Such experiments complement and help comprehension of field investigations. We estimated, by image analysis, the first two moments of small plumes traveling through a two-dimensional, heterogeneous medium with strongly anisotropic correlation structure. Three steady state regimes were analyzed. Two main conclusions were drawn. First, low saturation led to very large heterogeneity and to strong preferential flow. Thus the description of the flow paths and the prediction of the solute arrival times require, in this case, more accurate knowledge about the topological structure. Second, saturation-dependent macroscopic anisotropy is an essential element of transport in unsaturated media. For this reason, small structural soil features should be properly upscaled to give appropriate effective soil parameters to be input in transport models.

Family models of independence/interdependence and their intergenerational similarity in Germany, Turkey, and India

Family change theory suggests three ideal-typical family models characterized by different combinations of emotional and material interdependencies in the family. Its major proposition is that in economically developing countries with a collectivistic background a family model of emotional interdependence emerges from a family model of complete interdependence. The current study aims to identify and compare patterns of family-related value orientations related to family change theory across three cultures and two generations. Overall, N = 919 dyads of mothers and their adolescent children from Germany, Turkey, and India participated in the study. Three clusters were identified representing the family models of independence, interdependence, and emotional interdependence, respectively. Especially the identification of an emotionally interdependent value pattern using a person-oriented approach is an important step in the empirical validation of family change theory. The preference for the three family models differed across as well as within cultures and generations according to theoretical predictions. Dyadic analyses pointed to substantial intergenerational similarities and also to differences in family models, reflecting both cultural continuity as well as change in family-related value orientations.

Three-dimensional printing creates models for surgical planning of aortic valve replacement after previous coronary bypass grafting.

PURPOSE Resternotomy for aortic valve replacement in patients with previous coronary artery bypass grafting and an internal mammary artery graft may be a surgical problem. Thus, we are exploring the effect of using rapid prototyping techniques for surgical planning and intraoperative orientation during aortic valve replacement after previous coronary artery bypass grafting (CABG). DESCRIPTION As a proof of concept, we studied a patient who had undergone CABG 5 years earlier. At that time the patient received a left internal mammary artery graft to the left anterior descending artery and a venous graft to the right coronary artery. Now the patient required aortic valve replacement due to symptomatic aortic valve stenosis. The left internal mammary artery bypass and the right coronary artery bypass were patent and showed good flow in the angiography. The patient was examined by 128-slice computed tomography. The image data were visualized and reconstructed. Afterwards, a replica showing the anatomic structures was fabricated using a rapid prototyping machine. EVALUATION Using data derived from 128-slice computed tomography angiography linked to proprietary software, we were able to create three-dimensional reconstructions of the vascular anatomy after the previous CABG. The models were sterilized and taken to the operating theatre for orientation during the surgical procedure. CONCLUSIONS Stereolithographic replicas are helpful for choosing treatment strategies in surgical planning and for intraoperative orientation during reoperations of patients with previous CABG.

Modeling of ore-forming and geoenvironmental systems: Roles of fluid flow and chemical reaction processes

Ore-forming and geoenviromental systems commonly involve coupled fluid flowand chemical reaction processes. The advanced numerical methods and computational modeling have become indispensable tools for simulating such processes in recent years. This enables many hitherto unsolvable geoscience problems to be addressed using numerical methods and computational modeling approaches. For example, computational modeling has been successfully used to solve ore-forming and mine site contamination/remediation problems, in which fluid flow and geochemical processes play important roles in the controlling dynamic mechanisms. The main purpose of this paper is to present a generalized overview of: (1) the various classes and models associated with fluid flow/chemically reacting systems in order to highlight possible opportunities and developments for the future; (2) some more general issues that need attention in the development of computational models and codes for simulating ore-forming and geoenviromental systems; (3) the related progresses achieved on the geochemical modeling over the past 50 years or so; (4) the general methodology for modeling of oreforming and geoenvironmental systems; and (5) the future development directions associated with modeling of ore-forming and geoenviromental systems.

Measurement of the distributions of event-by-event flow harmonics in lead-lead collisions at = 2.76 TeV with the ATLAS detector at the LHC

The distributions of event-by-event harmonic flow coefficients v_n for n=2-4 are measured in sqrt(s_NN)=2.76 TeV Pb+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using charged particles with transverse momentum pT> 0.5 GeV and in the pseudorapidity range |eta|<2.5 in a dataset of approximately 7 ub^-1 recorded in 2010. The shapes of the v_n distributions are described by a two-dimensional Gaussian function for the underlying flow vector in central collisions for v_2 and over most of the measured centrality range for v_3 and v_4. Significant deviations from this function are observed for v_2 in mid-central and peripheral collisions, and a small deviation is observed for v_3 in mid-central collisions. It is shown that the commonly used multi-particle cumulants are insensitive to the deviations for v_2. The v_n distributions are also measured independently for charged particles with 0.51 GeV. When these distributions are rescaled to the same mean values, the adjusted shapes are found to be nearly the same for these two pT ranges. The v_n distributions are compared with the eccentricity distributions from two models for the initial collision geometry: a Glauber model and a model that includes corrections to the initial geometry due to gluon saturation effects. Both models fail to describe the experimental data consistently over most of the measured centrality range.

ANALYTICAL MODELS OF EXOPLANETARY ATMOSPHERES. I. ATMOSPHERIC DYNAMICS VIA THE SHALLOW WATER SYSTEM

Within the context of exoplanetary atmospheres, we present a comprehensive linear analysis of forced, damped, magnetized shallow water systems, exploring the effects of dimensionality, geometry (Cartesian, pseudo-spherical, and spherical), rotation, magnetic tension, and hydrodynamic and magnetic sources of friction. Across a broad range of conditions, we find that the key governing equation for atmospheres and quantum harmonic oscillators are identical, even when forcing (stellar irradiation), sources of friction (molecular viscosity, Rayleigh drag, and magnetic drag), and magnetic tension are included. The global atmospheric structure is largely controlled by a single key parameter that involves the Rossby and Prandtl numbers. This near-universality breaks down when either molecular viscosity or magnetic drag acts non-uniformly across latitude or a poloidal magnetic field is present, suggesting that these effects will introduce qualitative changes to the familiar chevron-shaped feature witnessed in simulations of atmospheric circulation. We also find that hydrodynamic and magnetic sources of friction have dissimilar phase signatures and affect the flow in fundamentally different ways, implying that using Rayleigh drag to mimic magnetic drag is inaccurate. We exhaustively lay down the theoretical formalism (dispersion relations, governing equations, and time-dependent wave solutions) for a broad suite of models. In all situations, we derive the steady state of an atmosphere, which is relevant to interpreting infrared phase and eclipse maps of exoplanetary atmospheres. We elucidate a pinching effect that confines the atmospheric structure to be near the equator. Our suite of analytical models may be used to develop decisively physical intuition and as a reference point for three-dimensional magnetohydrodynamic simulations of atmospheric circulation.