cssi/SciSciGPT-SciSciNet huggingface dataset:
Acute bleeding complications in patients after hematopoietic stem cell transplantation with prophylactic platelet transfusion triggers of 10 x 10(9) and 20 x 10(9) per L.

BACKGROUND: Prophylactic platelet (PLT) transfusions are given as a standard care in patients with hematologic malignancies undergoing hematopoietic stem cell transplantation (HSCT). This retrospective analysis evaluates utilization of blood transfusions, risk of bleeding, and survival in 480 HSCT patients at 10 × 109 and 20 × 109 per L prophylactic trigger levels. STUDY DESIGN AND METHODS: A total of 224 patients received prophylactic PLT transfusions at 20 × 109 per L threshold (1997-1998, SP1); 256 patients had prophylaxis at 10 × 109 per L (1999-2001, SP2). Bleeding scores were assigned daily. RESULTS: A slight reduction in PLT transfusions per patient in SP2 compared with SP1 was not statistically significant (odds ratio, 0.82; 95% confidence interval, 0.51-1.33; p = 0.416), yet a significantly higher proportion of patients in SP2 had PLT counts less than or equal to 10 × 109 per L compared to SP1 (p < 0.001). In patients who bled, however, there was no excess exposure to low PLT counts before bleeding started. A substantial number of patients who bled received PLT transfusions above the goal before bleeding started (82.9% in SP2, 41.5% in SP1) because of medical complications that associated with increased risk of bleeding. Bleeding incidence was similar in both study periods (21.9% in SP1, 16.4% in SP2; p = 0.526). Bleeding was significantly associated with reduced survival in both study periods. CONCLUSIONS: Patients who bled were usually placed on a higher threshold before the onset of their major bleeding event and were not exposed to additional risk of bleeding from thrombocytopenia. Similarity in bleeding incidence between study periods appears to associate with adjustments to high-risk conditions and may not reflect consequences of the lower transfusion threshold.
Kinetic Evaluation of Cell Membrane Hydrolysis during Apoptosis by Human Isoforms of Secretory Phospholipase A2

Some isoforms of secretory phospholipase A2 (sPLA2) distinguish between healthy and damaged or apoptotic cells. This distinction reflects differences in membrane physical properties. Since various sPLA2 isoforms respond differently to properties of artificial membranes such as surface charge, they should also behave differently as these properties evolve during a dynamic physiological process such as apoptosis. To test this idea, S49 lymphoma cell death was induced by glucocorticoid (6-48 h), thapsigargin (3-4 h) or calcium ionophore. Rates of membrane hydrolysis catalyzed by various concentrations of snake venom and human groups IIa, V, and X sPLA2 were compared after each treatment condition. The data were analyzed using a model that evaluates the adsorption of enzyme to the membrane surface and subsequent binding of substrate to the active site. Results were compared temporally to changes in membrane biophysics and composition. Under control conditions, membrane hydrolysis was confined to the few unhealthy cells present in each sample. Increased hydrolysis during apoptosis and necrosis appeared to reflect substrate access to adsorbed enzyme for the snake venom and group X isoforms corresponding to weakened lipid-lipid interactions in the membrane. In contrast, apoptosis promoted initial adsorption of human groups V and IIa concurrent with phosphatidylserine exposure on the membrane surface. However, this observation was inadequate to explain the behavior of the groups V and IIa enzymes toward necrotic cells where hydrolysis was reduced or absent. The response to endoplasmic reticulum stress (thapsigargin) was intermediate between that observed for glucocorticoid and ionomycin. Thus, a combination of changes in cell membrane properties during apoptosis and necrosis capacitates the cell for hydrolysis differently by each isoform.
Inhibition of mitogen-induced lymphocyte blastogenesis by serum from tumor-bearing animals: changes with tumor growth.

Abstract Serum from rats bearing hepatoma 5123 D was found to be inhibitory to the mitogen-induced blastogenic response of normal rat peripheral blood lymphocytes, and this inhibition increased with increasing tumor size. Tumor-bearer serum inhibited the phytohemagglutinin and concanavalin A responses at an earlier stage of tumor growth than the response to dextran sulfate. The concentration of phytohemagglutinin eliciting maximal incorporation of tritiated thymidine was 5 μl/ml for lymphocytes cultured in normal serum and 15 μl/ml for tumor-bearer serum. For concanavalin A the best response was at 2·5 μg/ml in both sera. For dextran sulfate 40 μg/ml elicited the maximal incorporation in normal serum while 20 μg/ml was found for tumor-bearer serum. In all cases, the maximal response at all mitogen levels was significantly less when tumor-bearer as opposed to normal serum was used. The inhibitory component(s) in the tumor-bearer serum was heat stable, nondializable and could be removed from the serum by exposure to normal lymphocytes.
Spawning Substrate Size, Shape, and Siltation Influence Walleye Egg Retention

Abstract We compared Walleye Sander vitreus egg retention among varying rock treatments placed in a hydraulic flume to test the influence of spawning substrate shape and size on egg retention and the influence of substrate siltation on egg adhesiveness. Egg loss from suboptimal spawning substrates has been hypothesized as a substantial source of mortality during the incubation period. To investigate the influence of substrate size and shape on Walleye egg retention, known numbers of Walleye eggs were pipetted onto rock substrate in a hydraulic flume and exposed to flowing water conditions. Eggs scoured from the substrate during each trial were collected and enumerated. Egg retention was higher in angular crushed limestone than in round glacial till and greater in coarse gravel than in larger size-classes, under all water velocity regimes. Angular coarse gravel had the highest egg retention rate (mean ± SD, 66.9 ± 3.7%), and round very coarse gravel had the lowest egg retention rate (47.0 ± 3.1%) of all th...
Approaching the “Resistant:” Exploring East Asian International Students’ Perceptions of Therapy and Help-Seeking Behavior Before and After They Arrived in the United States

In this study we investigated cultural, familial, and individual beliefs that influenced international students’ perceptions of therapy and help-seeking behaviors. Included were changes in perception or behavior before and after the students came to the US, and factors that influenced help-seeking behaviors. Six international students from East Asian countries where English is a foreign language, including Taiwan, Mainland China, Japan, and South Korea, were interviewed. We used semi-structured interviews and participant observations for collecting data. The findings indicated changes after students came to the US. Further discussions focus on encouraging and discouraging factors relative to seeing therapists, and culturally sensitive interventions for family therapy clinicians.
DEVELOPMENT OF A DICHOTOMOUS SLIT NOZZLE VIRTUAL IMPACTOR

Abstract A high-volume slit nozzle virtual impactor has been developed to collect fine and coarse particles. The size cut-off and particle loss characteristics of the developed slit virtual impactor agree well with those of the 16.7 l min −1 commercially available dichotomous sampler. The effects of various flow and physical design parameters on the collection of both fine and coarse particles have been investigated. The results of these tests indicated that many of the theoretical principles established for round nozzle virtual impactors can be successfully applied to slit nozzle virtual impactors. However, the effects of the flow volume and Reynolds number (Re) on the cut-off behavior and particle losses are more pronounced for slit virtual impactors. The impactor's particle size cutpoint decreased as the total inlet flow and Re increased. For Re 7000, losses of fine particles were significant, while coarse particle losses were low. Changes in the minor-to-total flow ratio and collection slit width also affected particle losses.
A General Equation for Correlating the Thermophysical Properties of n-Paraffins, n-Olefins, and Other Homologous Series. 3. Asymptotic Behavior Correlations for Thermal and Transport Properties

In this final paper of the series, asymptotic behavior correlations (ABCs) are presented for thermal properties (ideal-gas enthalpy and free energy of formation, ideal-gas heat capacity, enthalpy of vaporization, and liquid heat capacity) and for transport properties (liquid viscosity, thermal conductivity, and surface tension). The theoretical basis for asymptotic behavior of these properties is discussed. The correlations were developed using literature data for n-paraffins and n-olefins (1-alkenes) and give accurate and consistent predictions. They are preferable to existing correlations in most instances. For specific heat, viscosity, thermal conductivity, and surface tension, comparisons are made with high molecular weight, linear polyethylenes and other long-chain molecules.
Gene-Specific Repression of Proinflammatory Cytokines in Stimulated Human Macrophages by Nuclear IκBα

We have previously shown that increased nuclear accumulation of IκBα inhibits NF-κB activity and induces apoptosis in human leukocytes. In this study, we wanted to explore the possibility that the nucleocytoplasmic distribution of IκBα can be used as a therapeutic target for the regulation of NF-κB–dependent cytokine synthesis. Treatment of LPS-stimulated human U937 macrophages with an inhibitor of chromosome region maintenance 1-dependent nuclear export, leptomycin B, resulted in the increased nuclear accumulation of IκBα and inhibition of NF-κB DNA binding activity, caused by the nuclear IκBα-p65 NF-κB interaction. Surprisingly, however, whereas mRNA expression and cellular release of TNF-α, the β form of pro-IL-1 (IL-1β), and IL-6 were inhibited by the leptomycin B-induced nuclear IκBα, IL-8 mRNA expression and cellular release were not significantly affected. Analysis of in vivo recruitment of p65 NF-κB to NF-κB–regulated promoters by chromatin immunoprecipitation in U937 cells and human PBMCs indicated that although the p65 recruitment to TNF-α, IL-1β, and IL-6 promoters was inhibited by the nuclear IκBα, p65 recruitment to IL-8 promoter was not repressed. Chromatin immunoprecipitation analyses using IκBα and S536 phosphospecific p65 NF-κB Abs demonstrated that although the newly synthesized IκBα induced by postinduction repression is recruited to TNF-α, IL-1β, and IL-6 promoters but not to the IL-8 promoter, S536-phosphorylated p65 is recruited to IL-8 promoter, but not to TNF-α, IL-1β, or IL-6 promoters. Together, these data indicate that the inhibition of NF-κB–dependent transcription by nuclear IκBα in LPS-stimulated macrophages is gene specific and depends on the S536 phosphorylation status of the recruited p65 NF-κB.
Recovery-Based Discontinuous Galerkin for Navier-Stokes Viscous Terms

Recovery-based discontinuous Galerkin (RDG) is presented as a new generation of discontinuous Galerkin (DG) methods for diusion. The recovery concept is easily understood and integrated; in particular, RDG does not require additional data structures for surrogate variables and lifting operators, nor intricate manipulation of the partial dierential equations, as is the case with Local Discontinuous Galerkin. In our previous papers we have illustrated RDG’s remarkable accuracy and stability for scalar diusion problems via numerical experiment and Fourier analysis. This paper demonstrates RDG’s ability to solve the 2-D Navier-Stokes equations. We extend the original recovery concept for the diusion ux; recovery is now used for solution enhancement. Solution enhancement via recovery is attractive because the subroutines can be used repetitively until a desired level of enhancement is achieved. We then present numerical results for a 2-D nonlinear equation and the Navier-Stokes equations. Lastly, we compare the various RDG schemes by Fourier analysis.
Pharmacokinetics of Genetically Engineered Antibody Forms Using Positron Emission Tomography

In the last grant period we have focused on multi-step targeting methodologies (MST), as a method for delivery of high dose to the tumor, with low dose to the bone marrow. We have explored uptake in colorectal, pancreatic and prostate cancer, using an special preparation, developed in collaboration with NeoRex A high tumor/bone marrow ratio is clearly achieved with MST, but with a cost, namely the higher dose to normal kidney. For this reason, we have in particular, (a) looked dosimetry for both tumor and normal organ, and especially renal dosimetry, which appears to be the target organ, for Y-90. (b) In parallel with this we have explored the dosimetry of very high dose rate radionuclides, including Holmium-166. (c) In addition, with NaiKong Cheung, we have developed a new MST construct based on the anti-GD2 targeting 5F11; (d) we have successfully completed development of s-factor tables for mice. In summary, renal dosimetry is dominated by about 4-5% of the injected dose being held long-term in the renal cortex, probably in the proximal tubule, due to the universal uptake of small proteins. This appears to be a function of a biotynlated protein binding of the strept-avidin construct, to HSP70. This corticalmore » uptake has caused us to reconsider renal dosimetry as a whole, with the smaller mass of the cortex, rather than the whole kidney, as the target organ. These insights into dosimetry will be of great importance as MST, becomes more common in clinical practice.« less
Minimizing Probing Cost and Achieving Identifiability in Network Link Monitoring

Continuously monitoring the link performance is important to network diagnosis. Recently, active probes sent between end systems are widely used to monitor the link performance. In this paper, we address the problem of minimizing the probing cost and achieving identifiability in link monitoring. Given a set of links to monitor, our objective is to select as few probing paths as possible to cover all of them, and the selected probing paths can uniquely identify all identifiable links being monitored. We propose an algorithm based on the linear system model to find out all sets of probing paths that can uniquely identify an identifiable link. We extend the bipartite model to reflect the relation between a set of probing paths and the link that can be uniquely identified. Through the extended bipartite model, our optimization problem is transformed into the classic set cover problem, which is NP-hard. Therefore, we propose a heuristic based algorithm to greedily select the probing paths. Our method eliminates two types of redundant probing paths, i.e., those that can be replaced by others and those that cannot be used to achieving identifiability. Simulations based on real network topologies show that our approach can achieve identifiability with very low probing cost. Compared with prior work, our method is more general and has better performance.
Localization of pigment epithelium derived factor (PEDF) in developing and adult human ocular tissues.

Results: In developing retinas (7.4 to 21.5 fetal weeks, Fwks), pAb anti-PEDF labeled retinal pigment epithelium (RPE) granules, developing cones, some neuroblasts and many cells in the ganglion cell layer (GCL). In adult retinas, pAb antiPEDF labeled rod and cone cytoplasm and nuclei of rods but not cones. Cells in the INL and GCL, choroid, corneal epithelium and endothelium, and ciliary body were also pAb PEDF-positive. Preadsorption of pAb anti-PEDF with the immunizing peptide blocked specific labeling in retina and other tissues, except for photoreceptor outer segments. In agreement with the immunolocalization with pAb anti-PEDF, in situ hybridization revealed PEDF mRNA in the RPE, photoreceptors, inner nuclear layer cells and ganglion cells in adult retina. In developing retinas 18 Fwks and older, and in adult retinas, mAb anti-PEDF labeled the interphotoreceptor matrix (IPM). Western blots of retina, cornea, and ciliary body/iris with pAb anti-PEDF produced several bands at about 46 kDa. With mAb anti-PEDF, retina produced one band at about 46 kDa; cornea and ciliary body/iris had several bands at about 46 kDa. Conclusions: PEDF, originally reported as a product of RPE cells, is present in photoreceptors and inner retinal cell types in developing and adult human eyes. Photoreceptors and RPE may secrete PEDF into the IPM.
Microrheology of highly crosslinked microtubule networks is dominated by force-induced crosslinker unbinding

We determine the time- and force-dependent viscoelastic responses of reconstituted networks of microtubules that have been strongly crosslinked by biotin–streptavidin bonds. To measure the microscale viscoelasticity of such networks, we use a magnetic tweezers device to apply localized forces. At short time scales, the networks respond nonlinearly to applied force, with stiffening at small forces, followed by a reduction in the stiffening response at high forces, which we attribute to the force-induced unbinding of crosslinks. At long time scales, force-induced bond unbinding leads to local network rearrangement and significant bead creep. Interestingly, the network retains its elastic modulus even under conditions of significant plastic flow, suggesting that crosslinker breakage is balanced by the formation of new bonds. To better understand this effect, we developed a finite element model of such a stiff filament network with labile crosslinkers obeying force-dependent Bell model unbinding dynamics. The coexistence of dissipation, due to bond breakage, and the elastic recovery of the network is possible because each filament has many crosslinkers. Recovery can occur as long as a sufficient number of the original crosslinkers are preserved under the loading period. When these remaining original crosslinkers are broken, plastic flow results.
Coagulation abnormalities in 5 cats with naturally occurring cytauxzoonosis

Objective To characterize hemostasis and determine if disseminated intravascular coagulation (DIC) is present in cats with cytauxzoonosis. Design Cross-sectional study. Setting University teaching hospital. Animals Five client-owned cats with cytologic and PCR-confirmed cytauxzoonosis. Interventions None. Measurements and Main Results Admission samples were collected for hemostasis testing including platelet count, activated partial thromboplastin time, prothrombin time, fibrinogen, antithrombin (AT), d-dimer, protein C, plasminogen, antiplasmin, factors VII, VIII, IX, X, and XI, von Willebrand factor, and thromboelastography. Results were compiled for combined criteria used to define DIC, and all 5 cats satisfied criteria using a previously described modified scoring system for DIC in cats. The abnormalities found in all 5 cats included thrombocytopenia, low protein C activity, and prolonged prothrombin time; however, none of the cats had low AT activity. None of the cats had clinical signs of hemorrhage despite thrombocytopenia, coagulation factor deficiency (5/5 cats), and thromboelastographic evidence of hypocoagulability (2/5 cats). Three of 5 cats survived to hospital discharge. The nonsurvivors had disseminated cytauxzoonosis with schizont-laden macrophages in vessels of various organs. Conclusions This is the first report that comprehensively describes the hemostastic status of cats with naturally occurring infection with Cytauxzoon felis. All 5 cats had laboratory evidence of overt DIC. Unlike human and canine models of sepsis-induced DIC, AT deficiency was not found in this series of cats. Further research is warranted to investigate therapeutic strategies targeting thrombotic DIC to improve survival in cats with cytauxzoonosis.
Responding to Changing Situations: Learning Automata for Sensor Placement

Security issues have received increasing attention in recent years. Due to the difficulty of predicting where a terror event will occur, it is a great challenge to develop methods of detection that preempt attack. Sensors are one such method. However, questions of effective sensor placement remain?it is hard to determine where to place sensors because of uncertainty over the location of an attack. In this paper we use the intruders' behavioral constraints in the face of environmental factors as input to a learning algorithm that optimizes sensor placement. We show through simulation results that this algorithm can dynamically optimize placement by letting sensors make local decisions about where to move in situ. The resulting configurations are more or less equivalent to those achieved by the global optimization of sensor placement. The technique is superior in the sense that re-optimization happens continuously, and can be done with distributed control. Also, in many situations the configurations achieved are better than spacing sensors equally: detection rates are far higher.
Radiometric detection of direct-sequence spread spectrum signals with interference excision using the wavelet transform

One of the most important properties of direct-sequence spread spectrum signals (DSSS) is their low probability of intercept. Determination of the presence of such signals can be performed by radiometer-based intercept receivers that detect the signal's presence by measuring received power. However, conventional intercept receivers often fail when they operate in the presence of narrow-band interference because of their inability to differentiate between jammer and DSSS signal energy. An intercept receiver which employs wavelet transform domain-based excision is described. The receiver detects BPSK DSSS signals in the presence of narrow-band interference by employing adaptive interference rejection techniques to suppress the interference before measuring power. The improvement in the system performance over that of conventional radiometric detection only is shown by presenting numerical simulation results in the form of receiver operating characteristics. Performance is also compared to that for intercept receivers that use FFT-based excision systems techniques. >
Tectonic setting of the Jurassic Smartville and Slate Creek complexes, northern Sierra Nevada, California

Jurassic ophiolitic complexes in California and Oregon are widely distributed outboard of a Jurassic and older continental margin. Whether these outboard complexes were exotic and collided with the Jurassic continental margin, or whether they were simply part of a wide forearc to a Jurassic continental magmatic arc, has long been at issue. We have studied two such complexes and crosscutting intrusions in the fault-bounded Central and Western belts of the northern Sierra Nevada. We report new and revised U-Pb (zircon) dates for the Early Jurassic and younger Slate Creek complex (ca. 203−171 Ma) in the Central belt; the Late Jurassic Smartville complex (159 ± 3 Ma) in the Western belt; and crosscutting intrusions ranging from Middle Jurassic to Early Cretaceous age. The new ages imply that the Central and Western belts have been part of the same terrane since Middle Jurassic time and that the fault separating them has accommodated only minor displacements since ca. 160 Ma. Isotopic compositions of common Pb indicate derivation from mantle sources, but evidence for inheritance of Pre-cambrian zircon is common in plutons within the Early and Late Jurassic complexes and in Middle Jurassic, Late Jurassic, and Early Cretaceous crosscutting intrusions. Although there are several potential sources for such contamination, the ages of the inherited zircon are consistent with a North American origin. This contamination would have been accomplished most plausibly near the North American margin.
Local structure prediction with local structure-based sequence profiles.

Motivation: A large body of experimental and theoretical evidence suggests that local structural determinants are frequently encoded in short segments of protein sequence. Although the local structural information, once recognized, is particularly useful in protein structural and functional analyses, it remains a difficult problem to identify embedded local structural codes based solely on sequence information. Results: In this paper, we describe a local structure prediction method aiming at predicting the backbone structures of nine-residue sequence segments. Two elements are the keys for this local structure prediction procedure. The first key element is the LSBSP1 database, which contains a large number of non-redundant local structure-based sequence profiles for nine-residue structure segments. The second key element is the consensus approach, which identifies a consensus structure from a set of hit structures. The local structure prediction procedure starts by matching a query sequence segment of nine consecutive amino acid residues to all the sequence profiles in the local structure-based sequence profile database (LSBSP1). The consensus structure, which is at the center of the largest structural cluster of the hit structures, is predicted to be the native state structure adopted by the query sequence segment. This local structure prediction method is assessed with a large set of random test protein structures that have not been used in constructing the LSBSP1 database. The benchmark results indicate that the prediction capacities of the novel local structure prediction procedure exceed the prediction capacities of the local backbone structure prediction methods based on the I-sites library by a significant margin. Availability: All the computational and assessment procedures have been implemented in the integrated computational system PrISM.1 (Protein Informatics System for Modeling). The system and associated databases ∗ To whom correspondence should be addressed. for LINUX systems can be downloaded from the website:
Correlation based learning from spike timing dependent plasticity

We explore a synaptic plasticity model where potentiation and depression are induced by precisely timed pairs of synaptic events and postsynaptic spikes. We include the observation that strong synapses undergo relatively less potentiation than weak synapses, whereas depression is independent of synaptic strength. After random stimulation the synaptic weights reach a stable equilibrium distribution. Competition can be introduced separately by a mechanism that scales synaptic strengths as a function of postsynaptic activity. The plasticity rules select inputs which have a strong correlation with other inputs. 2001 Published by Elsevier Science B.V.
Quantitative assessment of RASSF1A methylation as a putative molecular marker in papillary thyroid carcinoma

Background Epigenetic alterations such as DNA methylation are widespread cancer, contributing to tumorigenesis and acting as markers for prognostication. Papillary thyroid cancer (PTC) demonstrates tumor-specific methylation of numerous genes, including RASSF1A. Although the function of RASSF1A in PTC tumorigenesis is still being defined, quantitative evaluation of RASSF1A methylation and its correlation with tumor characteristics has not been performed. Methods Analysis of RASSF1A methylation was performed using quantitative polymerase chain reaction after methylation-dependent and -sensitive restriction enzyme digestion in PTC (n = 41) and normal (n = 18) thyroid tissue. Methylation was then evaluated for correlation with tumor size, stage, and multiple histopathologic characteristics. Results RASSF1A promoter hypermethylation was observed in nearly all PTC cases versus normal thyroid tissue, with mean hypermethylation 4.2 times greater in PTC (P Conclusion RASSF1A methylation differs in PTC compared with normal thyroid, is associated with multifocality, and is inversely correlated with extracapsular invasion. The ease of evaluating methylation status with minute amounts of DNA suggests a potential role for RASSF1A as a molecular marker for characterization of PTC histopathology.
Unequal Competition Among Chains of Supercenters: Kmart, Target, and Wal‐Mart

The three largest discount chains, Kmart, Target, and Wal-Mart, have adopted the supercenter format for expansion. This article examines the locations of and the competition among these supercenters. Wal-Mart has the greatest number of supercenters and is driving the expansion of the supercenter format. Both Kmart and Target have clustered their supercenters in a small number of metropolitan markets. In contrast to Wal-Mart and Kmart, Target has focused on a middle-class rather than a blue-collar clientele. Now Kmart is struggling following a declaration of bankruptcy. Wal-Mart has largely defeated its supercenter competitors and now is confronting the major grocery chains for grocery sales.
Ventricular Conduction and Long-Term Heart Failure Outcomes and Mortality in African Americans Insights From the Jackson Heart Study

Background—QRS prolongation is associated with adverse outcomes in mostly white populations, but its clinical significance is not well established for other groups. We investigated the association between QRS duration and mortality in African Americans. Methods and Results—We analyzed data from 5146 African Americans in the Jackson Heart Study stratified by QRS duration on baseline 12-lead ECG. We defined QRS prolongation as QRS≥100 ms. We assessed the association between QRS duration and all-cause mortality using Cox proportional hazards models and reported the cumulative incidence of heart failure hospitalization. We identified factors associated with the development of QRS prolongation in patients with normal baseline QRS. At baseline, 30% (n=1528) of participants had QRS prolongation. The cumulative incidences of mortality and heart failure hospitalization were greater with versus without baseline QRS prolongation: 12.6% (95% confidence interval [CI], 11.0–14.4) versus 7.1% (95% CI, 6.3–8.0) and 8.2% ...
Geospatial Human-environment Simulation through Integration of Massive Multiplayer Online Games and Geographic Information Systems

This article reports on the initial development of a generic framework for integrating Geographic Information Systems (GIS) with Massive Multi-player Online Gaming (MMOG) technology to support the integrated modeling of human-environment resource management and decision-making. We review Web 2.0 concepts, online maps, and games as key technologies to realize a participatory construction of spatial simulation and decision making practices. Through a design-based research approach we develop a prototype framework, “GeoGame”, that allows users to play board-game-style simulations on top of an online map. Through several iterations we demonstrate the implementation of a range of design artifacts including: real-time, multi-user editing of online maps, web services, game lobby, user-modifiable rules and scenarios building, chat, discussion, and market transactions. Based on observational, analytical, experimental and functional evaluations of design artifacts as well as a literature review, we argue that a MMO GeoGame-framework offers a viable approach to address the complex dynamics of human-environmental systems that require a simultaneous reconciliation of both top-down and bottom-up decision making where stakeholders are an integral part of a modeling environment. Further research will offer additional insight into the development of social-environmental models using stakeholder input and the use of such models to explore properties of complex dynamic systems.
Emollient Therapy for Newborn Infants—A Global Perspective

Abstract Research on emollient therapy as a strategy to reduce mortality in newborn infants is a global priority. This paper discusses the use of emollients on newborn infants. Since the question is “Should emollients be applied to newborn infants, particularly premature infants?” the focus is on reports that discussed some measure of skin condition such as skin grades, skin effects, transepidermal water loss (TEWL), or impact on infection/mortality. The investigations on the use of emollients for premature infants are reviewed. Consideration is also given to the infant caregiver interactions during the applicaton as the process itself may be important for achieving benefits on skin barrier development and integrity. The remaining questions and subjects of future research are presented.
Mechanisms for quality control of misfolded transmembrane proteins

To prevent the accumulation of misfolded and aggregated proteins, the cell has developed a complex network of cellular quality control (QC) systems to recognize misfolded proteins and facilitate their refolding or degradation. The cell faces numerous obstacles when performing quality control on transmembrane proteins. Transmembrane proteins have domains on both sides of a membrane and QC systems in distinct compartments must coordinate to monitor the folding status of the protein. Additionally, transmembrane domains can have very complex organization and QC systems must be able to monitor the assembly of transmembrane domains in the membrane. In this review, we will discuss the QC systems involved in repair and degradation of misfolded transmembrane proteins. Also, we will elaborate on the factors that recognize folding defects of transmembrane domains and what happens when misfolded transmembrane proteins escape QC and aggregate. This article is part of a Special Issue entitled: Protein Folding in Membranes.
Biomarkers for Radiation Pneumonitis Using Noninvasive Molecular Imaging.

Our goal is to develop minimally invasive biomarkers for predicting radiation-induced lung injury before symptoms develop. Currently, there are no biomarkers that can predict radiation pneumonitis. Radiation damage to the whole lung is a serious risk in nuclear accidents or in radiologic terrorism. Our previous studies have shown that a single dose of 15 Gy of x-rays to the thorax causes severe pneumonitis in rats by 6–8 wk. We have also developed a mitigator for radiation pneumonitis and fibrosis that can be started as late as 5 wk after radiation. Methods: We used 2 functional SPECT probes in vivo in irradiated rat lungs. Regional pulmonary perfusion was measured by injection of 99mTc-macroaggregated albumin. Perfused volume was determined by comparing the volume of distribution of 99mTc-macroaggregated albumin to the anatomic lung volume obtained by small-animal CT. A second probe, 99mTc-labeled Duramycin, which binds to apoptotic cells, was used to measure pulmonary cell death in the same rat model. Results: The perfused volume of lung was decreased by about 25% at 1, 2, and 3 wk after receipt of 15 Gy, and 99mTc-Duramycin uptake was more than doubled at 2 and 3 wk. There was no change in body weight, breathing rate, or lung histology between irradiated and nonirradiated rats at these times. Pulmonary vascular resistance and vascular permeability measured in isolated perfused lungs ex vivo increased at 2 wk after 15 Gy of irradiation. Conclusion: Our results suggest that SPECT biomarkers have the potential to predict radiation injury to the lungs before substantial functional or histologic damage is observed. Early prediction of radiation pneumonitis in time to initiate mitigation will benefit those exposed to radiation in the context of therapy, accidents, or terrorism.
Dual effect of fluid shear stress on volume-regulated anion current in bovine aortic endothelial cells

The key mechanism responsible for maintaining cell volume homeostasis is activation of volume-regulated anion current (VRAC). The role of hemodynamic shear stress in the regulation of VRAC in bovin...
Inhibition of endotoxin-induced depression of cellular proliferation by ascorbic acid.

AbstractPrevious studies have shown that cementum-bound endotoxin or endotoxin-like products from untreated periodontally involved teeth depress the proliferation of, and have direct toxic effects on, cultured fibroblasts. The purpose of this investigation was to study the effect(s) of ascorbate and several other compounds on the toxicity of commercially prepared endotoxin. The 3T6 fibroblasts were grown in Dulbecco—Vogt modification of Eagles' medium containing 10% heat-inactivated calf serum. Replicate cultures were prepared and grown for 5 days. The proliferation of endotoxin-challenged cells was monitored in the presence of either l-ascorbate, d-isoascorbate, dehydroascorbate, carbonylcyanide m-chlorophenylhydrazone, or cycloheximide. Under very specific conditions, ascorbate reversed the endotoxin-mediated depression of cellular proliferation. An uncoupler of oxidative phosphorylation, carbonylcyanide m-chlorophenylhydrazone also effectively reversed the effect of endotoxin while cycloheximide had no...
Analysis on Detection Results of Urine Lead of Enterprise Employees in a District of Guangzhou City during 2004—2007

[Objective]To understand the level of urine lead among workers in lead exposure enterprises in a district of Guangzhou city,provide the reference for control and surveillance of lead poisoning.[Methods]The detection records of urine lead in occupational physical examination in this district during 2004—2007 were reviewed and analyzed statistically,and the urine lead were tested by flameless atomic absorption spectrometry.[Results]Among 271 urine samples,4.8 % of urine lead level was ≥0.07 mg/L,and 95.2% was 0.07 mg/L.Among 13 workers whose urine lead levels was ≥ 0.07 mg/L,7 workers was in the formation post of the storage battery factory,accounted for 11.9%,3 workers was in the smear post of the storage battery factory,accounted for 4.6%,and the rest 3 workers was in the drying post and driving post of the storage battery factory,plating post of electroplating industry respectively,together accounted for 4.6% ( χ2=8.90,P0.01).There was difference in constituent ratio of urine lead which exceeded observation value among different posts.[Conclusion]Most of workers whose urine lead exceed standard was employees in the storage battery factory,and the formation and smear posts took a large proportion.It is suggested that the control and surveillance of lead poisoning should put emphasis in the storage battery factory in further.Because the urine lead level of workers exposed to lead was high,the occupational health monitoring should be strengthened among this population.
Understanding the eating-disordered patient: engaging the concrete

Anorexic patients typically present major obstacles when beginning psychotherapy, including a tendency to focus concretely on their food- and weight-related symptoms. The author seeks to clarify the meaning of this "concrete attitude" and presents a treatment approach that accepts the anorexic person's "limitations." The case of a 14-year-old anorexic girl illustrates how acceptance and understanding of the patient's concrete attitude, especially during the initial phase of treatment, can reduce the probability of a therapeutic impasse and can enhance the treatment process.
Genomic characterization of high-count MBL cases indicates that early detection of driver mutations and subclonal expansion are predictors of adverse clinical outcome

High-count monoclonal B-cell lymphocytosis (MBL) is an asymptomatic expansion of clonal B cells in the peripheral blood without other manifestations of chronic lymphocytic leukemia (CLL). Yearly, 1% of MBLs evolve to CLL requiring therapy; thus being critical to understand the biological events that determine which MBLs progress to intermediate/advanced CLL. In this study, we performed targeted deep sequencing on 48 high-count MBLs, 47 of them with 2-4 sequential samples analyzed, exploring the mutation status of 21 driver genes and evaluating clonal evolution. We found somatic non-synonymous mutations in 25 MBLs (52%) at the initial time point analyzed, including 12 (25%) with >1 mutated gene. In cases that subsequently progressed to CLL, mutations were detected 41 months (median) prior to progression. Excepting NOTCH1, TP53 and XPO1, which showed a lower incidence in MBL, genes were mutated with a similar prevalence to CLL, indicating the early origin of most driver mutations in the MBL/CLL continuum. MBLs with mutations at the initial time point analyzed were associated with shorter time-to-treatment (TTT). Furthermore, MBLs showing subclonal expansion of driver mutations on sequential evaluation had shorter progression time to CLL and shorter TTT. These findings support that clonal evolution has prognostic implications already at the pre-malignant MBL stage, anticipating which individuals will progress earlier to CLL.
Role of cell membrane transporters in the pharmacological treatment of Sickle cell anemia

T pharmacological management of any disease can be complex due the multitude of factors driving pharmacokinetic (PK) and pharmacodynamic (PD) properties of drugs. Sickle cell anemia (SCA) is particularly difficult to manage due to the complex pathophysiology that affects multiple organ systems. In order to improve current therapies and develop new drugs for the treatment of SCA, it is important to understand factors that modulate PK and PD. Recent studies have demonstrated that cell membrane transport proteins encoded by the family of ATP-binding cassette (ABC) genes and solute carrier (SLC) genes play an integral role in regulating PK and PD properties of oncology drugs. Transporters mediate cellular uptake and efflux of substrates which influence drug disposition as well as targeted and off-target drug effects. Variation in transporter function or expression contributes to inter-patientvariability in drug response and drug-drug or drug-food interactions. The oncology field is moving rapidly to further examine the impact of ABC and SLC transporters on drug distribution, toxicity, efficacy, and interactions for investigational and approved drugs. Likewise, pharmacological studies of commonly used drugs in hematology may help to improve treatment for SCA. Hydroxyurea, currently the only FDA-approved drug for the treatment of SCA, induces fetal hemoglobin expression and decreases sickle cell-related morbidity. However, PK and PD properties of hydroxyurea vary widely between patients, and the source of inter-patient variability remains largely unknown. Studies to elucidate PK and PD properties of hydroxyurea are needed. Data implicating transporters in the modulation of hydroxyurea pharmacology will be presented including (i) identification of specific transporters and (ii) demonstration of how transporter deficiency alters hydroxyurea PK. From these findings, it is evident that additional studies are warranted to investigate the role of transporters as determinants of hydroxyurea PK and PD responses. Knowledge gained from these and similar studies of hematological drugs may be particularly applicable for optimizing individual dosing regimens, predicting individual drug response, and avoiding drug-drug or drug-food interactions. All of which can help to improve the pharmacological treatment for SCA.
Introduction to the Special Section on Culture and Variants of Sex/Gender: Bias and Stigma

As a side effect of globalization, the ideological and religious heterogeneity of many local populations is increasing. This trend is particularly noticeable at tertiary-care medical centers serving patients with rare conditions such as somatic intersexuality or gender dysphoria and transgenderism (both with and without somatic intersexuality). This special section is designed to familiarize clinicians and researchers with culture-associated gender bias and stigma that may influence attitudes to individuals with somatic or behavioral gender atypicalities.
RNA secondary structures regulate three steps of Rho-dependent transcription termination within a bacterial mRNA leader

Transcription termination events in bacteria often require the RNA helicase Rho. Typically, Rho promotes termination at the end of coding sequences, but it can also terminate transcription within leader regions to implement regulatory decisions. Rho-dependent termination requires initial recognition of a Rho utilization (rut) site on a nascent RNA by Rho's primary binding surface. However, it is presently unclear what factors determine the location of transcription termination, how RNA secondary structures influence this process and whether mechanistic differences distinguish constitutive from regulated Rho-dependent terminators. We previously demonstrated that the 5' leader mRNA of the Salmonella corA gene can adopt two mutually exclusive conformations that dictate accessibility of a rut site to Rho. We now report that the corA leader also controls two subsequent steps of Rho-dependent termination. First, the RNA conformation that presents an accessible rut site promotes pausing of RNA polymerase (RNAP) at a single Rho-dependent termination site over 100 nt downstream. Second, an additional RNA stem-loop promotes Rho activity and controls the location at which Rho-dependent termination occurs, despite having no effect on initial Rho binding to the corA leader. Thus, the multi-step nature of Rho-dependent termination may facilitate regulation of a given coding region by multiple cytoplasmic signals.
Rapid Response Team Activations in Pediatric Surgical Patients.

Introduction The rapid response team (RRT) is a multidisciplinary team who evaluates hospitalized patients for concerns of nonemergent clinical deterioration. RRT evaluations are mandatory for children whose Pediatric Early Warning System (PEWS) score (assessment of child's behavior, cardiovascular and respiratory status) is ≥4. We aimed to determine if there were differences in characteristics of RRT calls between children who were admitted primarily to either medical or surgical services. We hypothesized that RRT activations would be called for less severely ill children with lower PEWS score on surgical services compared with children admitted to a medical service. Materials and Methods We performed a retrospective review of all children with RRT activations between January 2008 and April 2015 at a tertiary care pediatric hospital. We evaluated the characteristics of RRT calls and made comparisons between RRT calls made for children admitted primarily to medical or surgical services. Results A total of 2,991 RRT activations were called, and 324 (11%) involved surgical patients. Surgical patients were older than medical patients (median: 7 vs. 4 years; p p p p = 0.412). RRT evaluations did not differ between day and night shifts (52% day vs. 48% night; p = 0.17). All surgical patients and all but one medical patient survived the event; surgical patients were more likely to survive to hospital discharge (97 vs. 91%, p Conclusions RRT activations are rare events among pediatric surgical patients. When compared with medical patients, RRT evaluation is requested for surgical patients with a lower PEWS score and these children are less likely to require transfer to a higher level of care, suggesting that pediatric surgery team, families, and nursing staff may not be as comfortable with clinical deterioration.
NATURE OF THE PROTEIN CORE OF BOVINE, OVINE AND PORCINE SUBMAXILLARY MUCINS AND ITS IMPLICATIONS FOR PROTEIN SYNTHESIS*

Publisher Summary This chapter discusses the nature of the protein core of bovine, ovine, and porcine submaxillary mucins and describes its implications for protein synthesis. Protein biosynthesis occurs by a two-step mechanism involving the formation of small peptides at the ribosomes and their assembly by polymerases at the Golgi membrane. The existence of homologous peptides and proteins in the mucins from individual glands has important consequences for the concept of evolutionary processes. The lack of blood group activity for the inactive mucin can be expected to arise from the presence of carbohydrate chains shorter than for those for the H and A types. A limited number of synthesizing sites for peptides, containing 16 to 30 amino acids, can produce a pool of peptides from which an unlimited number of proteins can be assembled at a specific enzyme site for each protein. Specific short sequences needed for a particular function—for example, the basic chains of histones—can be separately synthesized and incorporated.