bluuebunny/crossref_metadata_2025 huggingface dataset:
FRAMESELF: an ontology‐based framework for the self‐management of machine‐to‐machine systems
Authors: Alaya Mahdi Ben , Monteil Thierry
Published: October 2013

Machine‐to‐machine (M2M) systems need to connect thousands of heterogeneous machines that are widely distributed and frequently evolve according to their environment changes. Keeping such systems alive is costly in terms of time and money. The increasing complexity of M2M communications places M2M development and research under strain. Autonomic computing paradigm is widely believed to be a promising solution to self‐manage this complexity. This paper proposes FRAMESELF, an ontology‐based framework designed for the self‐configuration of M2M communications. A variety of communication modules based on service‐oriented and event‐driven communication patterns is dynamically selected and configured in deployment plans. A generic and extensible control loop components diagram detailing the monitoring, analyzing, planning, and executing processes are provided. Ontology models describing the M2M architecture and M2M communication patterns are proposed. A smart metering use case is experimented to validate the proposed approach and to calculate the overload generated by FRAMESELF facing scalability. Copyright © 2013 John Wiley & Sons, Ltd.
Tracking moving objects using topographical indexing
Authors: Alamri Sultan , Taniar David , Safarb Maytham , Al‐Khalidi Haidar
Published: October 2013

With the increasing popularity of Global Positioning System (GPS) technologies, many applications have been developed that are able to browse and monitor their GPS tracks on mobile objects. However, a large number of applications focus only on the region (not the exact coordinate location) where mobile objects are located. Not only the exact coordinate locations of moving objects are not needed but also the exact coordinate locations may sometime be distorted because of the inaccuracy of tracking systems. Therefore, in this paper, we propose an efficient data structure index for the moving objects based on their regional location. The topographical outdoor‐tree (TO‐tree) is based on the connectivity (adjacency) between outdoor cells space. The proposed index can support and enable efficient query processing and efficient updates of moving objects in outdoor space cells. The TO‐tree can serve spatial, topological, and adjacency queries. Experiments suggest that the TO‐tree performs efficiently and incurs less update cost while maintaining satisfactory performance. Copyright © 2013 John Wiley & Sons, Ltd.
Development of a Green Supercapacitor Composed Entirely of Environmentally Friendly Materials
Authors: Dyatkin Boris , Presser Volker , Heon Min , Lukatskaya Maria R. , Beidaghi Majid , Gogotsi Yury
Published: October 2013

Owing to recent power‐ and energy‐density advances, higher efficiencies, and almost unlimited lifetimes, electrical double‐layer capacitors (EDLCs, also known as supercapacitors) are now used in a wide range of energy harvesting and storage systems, which include portable power and grid applications. Despite offering key performance advantages, many device components pose significant environmental hazards once disposed. They often contain fluorine, sulfur, and cyanide groups, which are harmful if discarded by using conventional landfill or incineration methods, and they are constructed by using multiple metallic parts, which contribute to a high ash content. We explore designs for a fully operational supercapacitor that incorporates materials completely safe to dispose of and easy to incinerate. The components, which include material alternatives for the current collector, electrolyte, separator, particle binder, and packaging, are all mutually compatible, and most of them exhibit better performance than commonly used materials. We selected a graphite foil as current collector, sodium acetate as electrolyte, an ester as porous membrane based on acetate cellulose, and polymers based on polyvinyl alcohol as environmentally benign solutions for device components. The presented materials all originate from simple and inexpensive source compounds, which decreases the environmental impact of their manufacture and renders them more viable for integration into commercial devices for large‐scale stationary and transportation energy storage applications.
Epidemic routing based on adaptive compression of vectors: efficient low‐delay routing for opportunistic networks based on adaptive compression of vectors
Authors: Ren Zhi , Peng Shuang , Chen Hong , Fang Jun , Chen Qianbin
Published: October 2013

In the study of routing in opportunistic networks, we find that there are some redundant overhead when the existing epidemic‐based routing algorithms exchange summary vectors (SVs) and request vectors (RVs), and store SVs. To address this issue, we propose an efficient low‐delay routing algorithm, epidemic routing based on adaptive compression of vectors (ERACV). Our proposed algorithm adaptively shortens the length of SVs and RVs by compressing the same bit sequences, optimizes the mechanism of exchanging SVs and RVs, and improves the order of transmitting data packets. Theoretical analysis verifies the effectiveness of ERACV in decreasing redundant overhead and packet delay. Simulation results show that ERACV reduces SVs’ storage and control overheads by at least 18.0% and 35.8%, respectively, as well as decreases the average end‐to‐end delay of data packets by more than 2.5%, as compared with epidemic routing algorithm and message transmission control scheme. Copyright © 2013 John Wiley & Sons, Ltd.
Meta‐analysis reveals profound responses of plant traits to glacial CO2 levels
Authors: Temme A. A. , Cornwell W. K. , Cornelissen J. H. C. , Aerts R.
Published: October 2013

A general understanding of the links between atmospheric CO2 concentration and the functioning of the terrestrial biosphere requires not only an understanding of plant trait responses to the ongoing transition to higher CO2 but also the legacy effects of past low CO2. An interesting question is whether the transition from current to higher CO2 can be thought of as a continuation of the past trajectory of low to current CO2 levels. Determining this trajectory requires quantifying the effect sizes of plant response to low CO2. We performed a meta‐analysis of low CO2 growth experiments on 34 studies with 54 species. We quantified how plant traits vary at reduced CO2 levels and whether C3 versus C4 and woody versus herbaceous plant species respond differently. At low CO2, plant functioning changed drastically: on average across all species, a 50% reduction in current atmospheric CO2 reduced net photosynthesis by 38%; increased stomatal conductance by 60% and decreased intrinsic water use efficiency by 48%. Total plant dry biomass decreased by 47%, while specific leaf area increased by 17%. Plant types responded similarly: the only significant differences being no increase in SLA for C4 species and a 16% smaller decrease in biomass for woody C3 species at glacial CO2. Quantitative comparison of low CO2 effect sizes to those from high CO2 studies showed that the magnitude of response of stomatal conductance, water use efficiency and SLA to increased CO2 can be thought of as continued shifts along the same line. However, net photosynthesis and dry weight responses to low CO2 were greater in magnitude than to high CO2. Understanding the causes for this discrepancy can lead to a general understanding of the links between atmospheric CO2 and plant responses with relevance for both the past and the future.
Matrix metalloproteinases and tissue damage in HIV‐tuberculosis immune reconstitution inflammatory syndrome
Authors: Tadokera Rebecca , Meintjes Graeme A. , Wilkinson Katalin A. , Skolimowska Keira H. , Walker Naomi , Friedland Jon S. , Maartens Gary , Elkington Paul T. G. , Wilkinson Robert J.
Published: October 2013

The HIV‐TB‐associated immune reconstitution inflammatory syndrome (TB‐IRIS) can complicate combined treatments for HIV‐1 and TB. Little is known about tissue damage in TB‐IRIS. Matrix metalloproteinases (MMPs) degrade components of the extracellular matrix and consequently may play a role in such immunopathology. Here we investigated the involvement of MMPs in TB‐IRIS. We determined MMP transcript abundance and secreted protein in Mycobacterium tuberculosis stimulated PBMCs from 22 TB‐IRIS patients and 22 non‐IRIS controls. We also measured MMP protein levels in corresponding serum and the effect of prednisone — which reduces the duration of symptoms in IRIS patients — or placebo treatment on MMP transcript and circulating MMP protein levels. PBMCs from TB‐IRIS had increased MMP‐1, ‐3, ‐7, and ‐10 transcript levels when compared with those of controls at either 6 or 24 h. Similarly, MMP‐1, ‐3, ‐7, and ‐10 protein secretion in stimulated cultures was higher in TB‐IRIS than in controls. Serum MMP‐7 concentration was elevated in TB‐IRIS and 2 weeks of corticosteroid therapy decreased this level, although not significantly. TB‐IRIS is associated with a distinct pattern of MMP gene and protein activation. Modulation of dysregulated MMP activity may represent a novel therapeutic approach to alleviate TB‐IRIS in HIV‐TB patients undergoing treatment.
Facile Synthesis and Electrochemical Properties of Co3S4‐Nitrogen‐Doped Graphene Nanocomposites for Supercapacitor Applications
Authors: Grace Andrews Nirmala , Ramachandran Rajendran , Vinoba Mari , Choi Song Yi , Chu Dae Hyun , Yoon Yeoil , Nam Sung Chan , Jeong Soon Kwan
Published: October 2013

Nanocomposites of Co3S4 grown on nitrogen‐doped graphene (NG) (Co3S4‐NG) have been prepared at various concentrations of NG. The supercapacitive behaviors of the developed nanocomposites were assessed with cyclic voltammetry and galvanostatic charge discharge techniques. The nanocomposites exhibit excellent capacitive behavior with a high specific capacitance of 2427 F/g at 2 mV/s in Co3S4‐NG‐7 composite (7 indicates the percentage weight ratio of NG). The superior electrochemical performances could be due to synergistic effects between Co3S4 and NG, high charge mobility and good flexibility of graphene structures. These results indicate that the developed hybrid materials are promising candidates for high performance energy applications.
Interaction Between DNA and Some Salicylic Acid Derivatives and Characterization of Their DNA Targets
Authors: Abedi M. , Bathaie S. Z. , Mousavi M. F.
Published: October 2013

A nanofiber polypyrrole (PPy) film was electrochemically deposited on a Pt electrode and used for immobilization of single‐stranded DNA (ssDNA) and investigation of hybridization events. Then, the interaction of DNA with four salicylic acid (SA) derivatives was studied with electrochemical methods. The oxidation peak of guanine was decreased by increasing the concentrations of salicylic acid derivatives. The binding constants of these compounds with four different sequences of DNA including different percentages of guanine‐cytosine and adenine‐thymine bases were calculated and it was clarified that sequences with higher percentage of adenine‐thymine bases have a higher binding constant in their interaction with SA derivatives.
Performance analysis of full duplex decode‐and‐forward cooperative relaying over Nakagami‐m fading channels
Authors: Sharma Prabhat Kumar , Garg Parul
Published: October 2013

This paper analyses the error and outage performances of a dual hop, decode‐and‐forward cooperative system where the relay is equipped with full duplex relaying capabilities in a generalised fading environment. We evaluate the error performance in terms of average symbol error rate for M‐ary phase shift keying and obtain the exact closed form expression for M = 2. We also derive the exact closed form expression for outage probability considering flat, independent but not necessarily identical Nakagami‐m fading channels for full duplex relaying. Copyright © 2013 John Wiley & Sons, Ltd.
Efficient second‐order time integration for single‐species aerosol formation and evolution
Authors: Winkelmann Christoph , Nordlund Markus , Kuczaj Arkadiusz K. , Stolz Steffen , Geurts Bernard J.
Published: October 2013

The dynamics of a single‐species aerosol composed of droplets in air is described in terms of nucleation, evaporation, condensation, and coagulation processes. We present a comprehensive overview of the Euler–Euler formulation, which gives rise to a model in which fast nucleation that initiates aerosol droplets co‐exists with comparably slow condensation. The latter process is responsible for the subsequent growth of the droplets. To accurately represent the dynamical consequences of the fast nucleation process, while retaining numerical efficiency, a new second‐order time‐integration method for the nucleation, evaporation, and condensation processes is proposed and analyzed. The new time‐integration method takes the form of a ‘corrected Euler forward’ method. It includes rapid nucleation bursts and their possible cessation within a time step Δt. If the current nucleation burst persists for longer than the next time step, it is included fully, whereas cessation of the nucleation burst within the next Δt implies corrections to the effective rates in the algorithm. The identification of these two situations corresponds to the physical mechanism by which nucleation of a supersaturated vapor is halted because of the progressing condensation onto the already formed droplets. The resulting time‐integration method is shown to be second‐order accurate in time, whereas the computational costs per time step were found to be increased by less than 25% compared with the Euler forward method. The new method is also applied in combination with advective transport of the aerosol forming vapor to investigate a front of rapid nucleation. Adopting robust first‐order upwinding for the spatial discretization, we arrive at a flexible method that shows an overall first‐order convergence in Δt. For the full, spatially dependent system motivated by an aerosol of water droplets in air, the computational benefits of the new time‐integration method over the Euler forward scheme, are a factor of about 10 improvements in accuracy at a given Δt and a similar factor in computing time when keeping the same level of accuracy. Copyright © 2013 John Wiley & Sons, Ltd.
Age‐ and gender‐related regional variations of human brain cortical thickness, complexity, and gradient in the third decade
Authors: Creze Maud , Versheure Leslie , Besson Pierre , Sauvage Chloe , Leclerc Xavier , Jissendi‐Tchofo Patrice
Published: October 2013

Brain functional and cytoarchitectural maturation continue until adulthood, but little is known about the evolution of the regional pattern of cortical thickness (CT), complexity (CC), and intensity or gradient (CG) in young adults. We attempted to detect global and regional age‐ and gender‐related variations of brain CT, CC, and CG, in 28 healthy young adults (19–33 years) using a three‐dimensional T1‐weighted magnetic resonance imaging sequence and surface‐based methods. Whole brain interindividual variations of CT and CG were similar to that in the literature. As a new finding, age‐ and gender‐related variations significantly affected brain complexity (P < 0.01) on posterior cingulate and middle temporal cortices (age), and the fronto‐orbital cortex (gender), all in the right hemisphere. Regions of interest analyses showed age and gender significant interaction (P < 0.05) on the temporopolar, inferior, and middle temporal‐entorrhinal cortices bilaterally, as well as left inferior parietal. In addition, we found significant inverse correlations between CT and CC and between CT and CG over the whole brain and markedly in precentral and occipital areas. Our findings differ in details from previous reports and may correlate with late brain maturation and learning plasticity in young adults' brain in the third decade. Hum Brain Mapp 35:2817–2835, 2014. © 2013 Wiley Periodicals, Inc.
FORECASTING DISCONNECTED EXCHANGE RATES
Authors: Berge Travis J.
Published: October 2013

The inability of empirical models to forecast exchange rates has given rise to the belief that exchange rates are disconnected from macroeconomic fundamentals. This paper addresses the potential disconnect by endogenously selecting forecast models from a broad set of fundamentals. The procedure shows that exchange rates are not disconnected from fundamentals, but fundamentals vary in their predictive content at different forecast horizons and for different currencies. Performing model selection out‐of‐sample is challenging. At short horizons, the method cannot outperform a random walk, although the performance is improved at long horizons. These findings are confirmed across currencies and forecast evaluation methods. Copyright © 2013 John Wiley & Sons, Ltd.
Screening and characterization of protease producing actinomycetes from marine saltern
Authors: Suthindhiran Krish , Jayasri Mangalam Achuthananda , Dipali Dipa , Prasar Apurva
Published: October 2013

In the course of systematic screening program for bioactive actinomycetes, an alkaline protease producing halophilic strain Actinopolyspora sp. VITSDK2 was isolated from marine saltern, Southern India. The strain was identified as Actinopolyspora based on its phenotypic and phylogenetic characters. The protease was partially purified using ammonium sulfate precipitation and subsequently by DEAE cellulose column chromatography. The enzyme was further purified using HPLC and the molecular weight was found to be 22 kDa as determined by SDS–PAGE analysis. The purified protease exhibited pH stability in a wide range of 4–12 with optimum at 10.0. The enzyme was found to be stable between 25 and 80 °C and displayed a maximum activity at 60 °C. The enzyme activity was increased marginally in presence of Mn2+, Mg2+, and Ca2+ and decreased in presence of Cu2+. PMSF and DFP completely inhibited the activity suggesting it belongs to serine protease. Further, the proteolytic activity was abolished in presence of N‐tosyl‐L‐lysine chloromethyl ketone suggesting this might be chymotrypsin‐like serine protease. The protease was 96% active when kept for 10 days at room temperature. The results indicate that the enzyme belong to chymotrypsin‐like serine protease exhibiting both pH and thermostability, which can be used for various applications in industries.
The radiative environment of the Tibetan Plateau
Authors: Wonsick Margaret M. , Pinker Rachel T.
Published: October 2013

The Tibetan Plateau, also known as the Qinghai—Tibetan Plateau, is a vast elevated plateau in Central Asia. It occupies an area of around 2.3 million km2 and has an average elevation of over 4500 m. The plateau is interspersed with mountain ranges, has a strong thermal effect on its atmospheric environment, and influences regional and global climate. As the depth of the atmosphere over the plateau is much smaller than its surroundings, the impact of solar radiation on heating the plateau is magnified. At present, observations of shortwave (SW) fluxes over the plateau are very meager and satellite estimates are very coarse. Therefore, estimating the role of radiation in the total heat budget of the plateau is difficult. We use an updated version of the University of Maryland Surface Radiation Budget model driven with observations from Meteosat‐5 to characterize clouds and surface SW radiative fluxes at high‐temporal and spatial resolution (hourly at 0.125°). Results are presented for a period of 5 years in terms of means and variability in space, time, and the context of the regional monsoon regimes. Maximum monthly mean values of SW flux near 360 Wm−2 occur in May and June, mainly in the western plateau. Minimum values of 120–150 Wm−2 are most widespread in December and January. An anomaly in clouds and SW fluxes in the plateau during the Indian monsoon drought year of 2002 is discovered and discussed. The objective of this study is to provide improved estimates of cloud amounts and radiative fluxes over the plateau in unprecedented detail and with consideration of the plateau conditions. It is anticipated that this information will be useful as a benchmark for the evaluation of numerical models that are known to have difficulties in this complex region and for hydrological modelling.
Statistical analysis of Indian rainfall and rice productivity anomalies over the last decades
Authors: Subash N. , Gangwar B.
Published: October 2013

Monsoon fluctuations have a reflective influence on rice productivity, which is the main foodgrain in India. The impact of El Niño on spatial variability of summer monsoon rainfall and thereby kharif rice productivity was analysed for the period 1974–2009. It was clear from the analysis that the delayed onset of monsoon along with El Niño has varied influences on rice productivity over different rice growing states as well as over India. Out of eight El Niño years, 6 years received deficit rainfall during monsoon season. But, the quantity of deficit varies from −20.3% in 2002 to −5.5% in 1991. The monthly distribution of monsoon rainfall shows higher frequency of deficit occurred during July and September. Interestingly, all El Niño years, except in 1997, September received deficit in rainfall which indicate the early withdrawal of monsoon. During 8 moderate and strong El Niño years, 5 years the kharif rice productivity falls below the technological trend ranging by between −4.3% in 1986 and −13.8% in 2002 over India. There exists a wide spatial variability of normalized kharif rice productivity anomaly during moderate El Niño event, with a maximum of −21.9% over Gujarat followed by −15.9% at Maharashtra. However, during the strong El Niño event, there is a maximum of −14.2% at Bihar to −6.6% over Maharashtra. The correlation between normalized monthly rainfall anomaly and rice productivity anomaly during the El Niño years indicated that July rainfall contributed 71% of the variations in rice productivity. Analysis of El Niño impact on spatial rice productivity may be useful for formulating farm‐level site specific management planning and policy decisions.
At What Depth Are The Properties of a Gypseous Forest Topsoil Affected By Burning?
Authors: Aznar Javier M. , González‐Pérez José A. , Badía David , Martí Clara
Published: October 2013

Wildfires represent one of the main factors of land degradation in Mediterranean environments having negative effects to several ecosystem services. In this work, the fire‐induced changes associated with depth (O horizon and Ah at 0–1, 1–2 and 2–3 cm depths) were studied in a gypseous soil under Aleppo pine forest. Topsoil monoliths were burned in an outdoor combustion tunnel simulating a fire of moderate intensity. In the O horizon, burning caused an immediate and significant decrease in water repellency (WR), total organic carbon (TOC) and pyrolyzed carbon (PyC) and an increase in total inorganic carbon. The Ah horizon was also significantly affected by fire, but mainly in its first shallower centimetre and with a different direction according to soil properties: TOC, gypsum, WR and PyC decreased, whereas soil aggregate stability and pH increased. Soil burning not only involved the loss of the pre‐fire organic matter content of the O horizon and the upper centimetre of the Ah horizon but also decreased their relative abundance of markers of resins, lignin and polysaccharides. Moreover, the soil burning exerted the cracking of alkylic long‐chain molecular series, some of them until the 2 cm Ah depth. The reduction of organic lipophilic molecules in the upper soil centimetre may be related to the fire‐induced decreases in WR. Moderate burning of the studied gypseous ochric horizon does not modify any of the properties studied at depths greater than 2 cm. Copyright © 2013 John Wiley & Sons, Ltd.
Increasing the Donor Pool: Consideration of Prehospital Cardiac Arrest in Controlled Donation After Circulatory Death for Liver Transplantation
Authors: Elaffandi Ahmed H. , Bonney Glenn K. , Gunson Bridget , Scalera Irene , Mergental Hynek , Isaac John R. , Bramhall Simon R. , Mirza Darius F. , Perera Thamara M. P.R. , Muiesan Paolo
Published: October 2013

Donor warm ischemia has implications for outcomes after liver transplantation (LT) using organs from donation after circulatory death (DCD) donors. Prehospital cardiac arrest (PHCA) before donation may generate a further ischemic insult. The aim of this single-center study of 108 consecutive DCD LT procedures was to compare the outcomes of PHCA and non-PHCA cohorts. A review of a prospectively collected database of all DCD grafts transplanted between January 2007 and October 2011 was undertaken to identify donors who had sustained PHCA. The unit policy was to consider such donors when transaminase levels were ≤4 times the normal range and had an improving trend. Twenty-six of the 108 DCD transplants were from DCD donors with PHCA, and 82 were in the non-PHCA cohort. A comparative analysis of the PHCA and non-PHCA cohorts showed better short-term results (a low incidence of acute kidney injury) for the PHCA group but satisfactory long-term results for both groups with no significant differences in graft or patient survival between them. In conclusion, a careful donor selection policy for including PHCA DCD donors with normalized liver function tests or transaminase levels ≤ 4 times the norm resulted in successful transplantation and could boost the donor pool with no adverse outcomes. Liver Transpl 20:63-71, 2014. © 2013 AASLD.
Multimodal Therapy Including Liver Transplantation for Hepatic Undifferentiated Embryonal Sarcoma
Authors: Walther Ashley , Geller James , Coots Abigail , Towbin Alexander , Nathan Jaimie , Alonso Maria , Sheridan Rachel , Tiao Greg
Published: October 2013

The outcomes of hepatic undifferentiated embryonal sarcoma (HUES) have historically been limited by persistent, unresectable disease and the subsequent development of disease resistance and dissemination. We present our institutional experience with HUES and assess current treatment trends and outcomes in the era of liver transplantation. We conducted a retrospective chart review of cases presenting with HUES at our institution over the past 10 years. The collected data included age, sex, presenting symptoms, imaging and the associated Pretreatment Extent of Disease (PRETEXT) score, pathology, chemotherapy, surgical interventions, and outcomes. Approval was obtained from the institutional review board of the Cincinnati Children's Hospital Medical Center. HUES was identified in 6 patients (4 males and 2 females) with a median age at diagnosis of 11 years (range = 7-13 years). Initial imaging was available for all but 1 patient. The PRETEXT stage for these patients ranged from II to III. One patient was diagnosed with lung metastases. Two patients underwent upfront resection, and 1 patient received neoadjuvant therapy and then conventional resection. Three patients were treated with orthotopic liver transplantation (OLT) after neoadjuvant chemotherapy (primary OLT in 2 cases and salvage OLT for local recurrence in 1 case). Two patients received posttransplant adjuvant chemotherapy. All 6 patients remained in clinical remission with a mean follow-up of 35 months (range = 12-84 months). In conclusion, OLT has rarely been reported as a treatment option for HUES. The addition of liver transplantation as a surgical option for treating patients with HUES can result in improved survival for patients whose tumors are initially unresectable or recur. Liver Transpl 20:191-199, 2014. © 2013 AASLD.
Transjugular Intrahepatic Portosystemic Shunts in Liver Transplant Recipients
Authors: Bonnel Alexander R. , Bunchorntavakul Chalermrat , Reddy Rajender K.
Published: October 2013

The insertion of a transjugular intrahepatic portosystemic shunt (TIPS) is a minimally invasive procedure used to relieve the signs and symptoms of portal hypertension in patients with liver disease. The most common indications for placement are refractory ascites and variceal hemorrhage. In properly selected candidates, TIPS placement can serve as a bridge to liver transplantation. Expertise in TIPS placement after transplantation has significantly increased, which has allowed the procedure to become a viable option for retransplant candidates suffering the consequences of recurrent portal hypertension due to portal vein thrombosis, recurrent liver disease, or hepatic venous outflow obstruction (HVOO). However, TIPSs in liver transplant recipients are associated with a lower clinical response rate and a higher rate of complications in comparison with patients with native liver disease, and they are, therefore, generally reserved for patients with a Model for End-Stage Liver Disease (MELD) score ≤ 15 and ≤ 12 in patients with HCV. The role of TIPS placement in nonliver transplant recipients has been well studied in large trials, and it translates well into clinical applicability to candidates for orthotopic liver transplantation (OLT). However, the experience with OLT recipients is heterogeneous and restricted to small series. Thus, we focus here on reviewing the current literature and discussing the proper use of TIPSs in liver transplant recipients. Liver Transpl 20:130-139, 2014. © 2013 AASLD.
Donor Hemodynamic Profile Presages Graft Survival in Donation After Cardiac Death Liver Transplantation
Authors: Abt Peter L. , Praestgaard Jens , West Sharon , Hasz Richard
Published: October 2013

Obligatory exposure to a period of warm ischemia is the defining feature of liver allografts from donation after cardiac death (DCD) donors. We explored novel methods for characterizing the dynamic aspects of donor warm ischemia that might be useful in assessing organ quality. The hemodynamic profile during donor warm ischemia was retrospectively studied for 110 Maastricht category III DCD donors. Three methods were used to summarize the hemodynamic changes after extubation: (1) the area under the systolic blood pressure curve (AUCSBP), (2) the slope of the systolic blood pressure regressed onto the time from extubation until cross-clamping, and (3) the slope of the systolic blood pressure regressed onto the time from extubation but calculated with only the values during the first 10 minutes after extubation (SBP10). Stepwise multivariate Cox models were created to study the association of these measures with graft survival. The duration of the donor warm ischemia time (23.6 ± 8.5 minutes) was not associated with graft survival (P = 0.35), although AUCSBP and SBP10 demonstrated significant associations (P = 0.02 and P = 0.05, respectively) in a univariate analysis. Multivariate regression models incorporating donor and recipient covariates indicated that among all covariates, SBP10 had the closest association with graft survival (hazard ratio = 1.08, P = 0.01). This association was even stronger when SBP10 was dichotomized into values above or below the median (−7.2 mm Hg/minute). Patients with SBP10s steeper than the median had an estimated 5-year graft survival rate of 76%, whereas patients with slopes less than the median had a 5-year survival rate of 45% (P < 0.007). In conclusion, the incorporation of novel methods for characterizing the donor warm ischemia time may help in selecting DCD liver allografts with favorable outcomes. Liver Transpl 20:165-172, 2014. © 2013 AASLD.
Oral mucosal health in liver transplant recipients and controls
Authors: Helenius-Hietala Jaana , Ruokonen Hellevi , Grönroos Lisa , Rissanen Harri , Vehkalahti Miira M. , Suominen Liisa , Isoniemi Helena , Meurman Jukka H.
Published: October 2013

Immunosuppressive drugs and other medications may predispose patients to oral diseases. Data on oral mucosal health in recipients of liver transplantation (LT) are limited. We, therefore, recruited 84 LT recipients (64 with chronic liver disease and 20 with acute liver failure) for clinical oral examinations in a cross-sectional, case-control study. Their oral health had been clinically examined before transplantation. The prevalence of oral mucosal lesions (OMLs) was assessed in groups with different etiologies of liver disease and in groups with different immunosuppressive medications, and these groups were compared to controls selected from a nationwide survey in Finland (n = 252). Risk factors for OMLs were evaluated with logistic regression. OMLs were more frequent in LT recipients versus controls (43% versus 15%, P < 0.001), and the use of steroids raised the prevalence to 53%. Drug-induced gingival overgrowth was the single most common type of lesion, and its prevalence was significantly higher for patients using cyclosporine A (CSA; 29%) versus patients using tacrolimus (TAC; 5%, P = 0.007); the prevalence was even higher with the simultaneous use of calcium channel blockers and CSA (47%) or TAC (8%, P = 0.002). Lesions with malignant potential such as drug-induced lichenoid reactions, oral lichen planus–like lesions, leukoplakias, and ulcers occurred in 13% of the patients with chronic liver disease and in 6% of the controls. Every third patient with chronic liver disease had reduced salivary flow, and more than half of all patients were positive for Candida; this risk was higher with steroids. In conclusion, the high frequency of OMLs among LT recipients can be explained not only by immunosuppressive drugs but also by other medications. Because dry mouth affects oral health and OMLs may have the potential for malignant transformation, annual oral examinations are indicated. Liver Transpl 20:72–80, 2014. © 2013 AASLD.
A systematic review and meta‐analysis of clinical variables used in Huntington disease research
Authors: Franciosi Sonia , Shim Yaein , Lau Margaret , Hayden Michael R. , Leavitt Blair R.
Published: October 2013

Treatment effect in Huntington disease (HD) clinical trials has relied on primary outcome measures such as total motor score or functional rating scales. However, these measures have limited sensitivity, particularly in pre‐ to early stages of the disease. We performed a systematic review of HD clinical studies to identify endpoints that correlate with disease severity. Using standard HD keywords and terms, we identified 749 published studies from 1993 to 2011 based on the availability of demographic, biochemical, and clinical measures. The average and variability of each measure was abstracted and stratified according to pre‐far, pre‐close, early, mild, moderate, and severe HD stages. A fixed‐effect meta‐analysis on selected variables was conducted at various disease stages. A total of 1,801 different clinical variables and treatment outcomes were identified. Unified Huntington Disease Rating Scale (UHDRS) Motor, UHDRS Independence, and Trail B showed a trend toward separation between HD stages. Other measures, such as UHDRS Apathy, Verbal Fluency, and Symbol Digit, could only distinguish between pre‐ and early stages of disease and later stages, whereas other measures showed little correlation with increasing HD stages. Using cross‐sectional data from published HD clinical trials, we have identified potential endpoints that could be used to track HD disease progression and treatment effect. Longitudinal studies, such as TRACK‐HD, are critical for assessing the value of potential markers of disease progression for use in future HD therapeutic trials. A list of variables, references used in this meta‐analysis, and database is available at http://www.cmmt.ubc.ca/research/investigators/leavitt/publications. © 2013 International Parkinson and Movement Disorder Society
Prefrontal seizures manifesting as motor stereotypies
Authors: McGonigal Aileen , Chauvel Patrick
Published: October 2013

Background

The definition of stereotypies traditionally does not include “epileptic automatisms.” However repetitive, sometimes rhythmic behaviors can occur during frontal lobe seizures in a reproducible pattern for a given patient. Thus, the concept of a frontostriatal “motor loop” could be relevant to repetitive ictal behaviors.

Methods

We describe 17 patients with frontal lobe epilepsy who presented with motor and/or verbal stereotypies and who were explored using depth electrodes (stereoelectroencephalography [SEEG]) in the context of epilepsy presurgical evaluation.

Results

Motor patterns were typically reproducible between seizures for a given patient. Distal motor stereotypies were associated with anterior prefrontal localization, and proximal stereotypies were associated with posterior prefrontal localization.

Conclusions

“Stereotypy” is a useful term to describe ictal repetitive behaviors produced by prefrontal seizure discharge. The expression of distal and proximal stereotypies follows a rostrocaudal gradient within the frontal lobes. Exploration of the cortical compartment of frontostriatal networks in epileptic patients offers a unique opportunity to study the mechanisms of stereotypies in vivo. © 2013 International Parkinson and Movement Disorder Society
Identification of Similar Binding Sites to Detect Distant Polypharmacology
Authors: Jalencas Xavier , Mestres Jordi
Published: October 2013

The ability of small molecules to interact with multiple proteins is referred to as polypharmacology. This property is often linked to the therapeutic action of drugs but it is known also to be responsible for many of their side effects. Because of its importance, the development of computational methods that can predict drug polypharmacology has become an important line of research that led recently to the identification of many novel targets for known drugs. Nowadays, the majority of these methods are based on measuring the similarity of a query molecule against the hundreds of thousands of molecules for which pharmacological data on thousands of proteins are available in public sources. However, similarity‐based methods are inherently biased by the chemical coverage offered by the active molecules present in those public repositories, which limits significantly their capacity to predict interactions with proteins structurally and functionally unrelated to any of the already known targets for drugs. It is in this respect that structure‐based methods aiming at identifying similar binding sites may offer an alternative complementary means to ligand‐based methods for detecting distant polypharmacology. The different existing approaches to binding site detection, representation, comparison, and fragmentation are reviewed and recent successful applications presented.
Extensions to In Silico Bioactivity Predictions Using Pathway Annotations and Differential Pharmacology Analysis: Application to Xenopus laevis Phenotypic Readouts
Authors: Liggi Sonia , Drakakis Georgios , Hendry Adam E. , Hanson Kimberley M. , Brewerton Suzanne C. , Wheeler Grant N. , Bodkin Michael J. , Evans David A. , Bender Andreas
Published: October 2013

The simultaneous increase of computational power and the availability of chemical and biological data have contributed to the recent popularity of in silico bioactivity prediction algorithms. Such methods are commonly used to infer the ‘Mechanism of Action’ of small molecules and they can also be employed in cases where full bioactivity profiles have not been established experimentally. However, protein target predictions by themselves do not necessarily capture information about the effect of a compound on a biological system, and hence merging their output with a systems biology approach can help to better understand the complex network modulation which leads to a particular phenotype. In this work, we review approaches and applications of target prediction, as well as their shortcomings, and demonstrate two extensions of this concept which are exemplified using phenotypic readouts from a chemical genetic screen in Xenopus laevis. In particular, the experimental observations are linked to their predicted bioactivity profiles. Predicted targets are annotated with pathways, which lead to further biological insight. Moreover, we subject the prediction to further machine learning algorithms, namely decision trees, to capture the differential pharmacology of ligand‐target interactions in biological systems. Both methodologies hence provide new insight into understanding the Mechanism of Action of compound activities from phenotypic screens.
Oscillating gradient spin‐echo (OGSE) diffusion tensor imaging of the human brain
Authors: Baron Corey A. , Beaulieu Christian
Published: October 2013

Purpose

The dependence of diffusion tensor imaging (DTI) eigenvalues and fractional anisotropy (FA) on short diffusion times was investigated using oscillating gradient spin echo (OGSE) and pulsed gradient spin echo (PGSE) DTI in the human brain in vivo.

Theory and Methods

DTI was performed in seven healthy volunteers at 4.7 Tesla (T) with b = 300 s/mm2 and diffusion times of 4.1 ms (OGSE 50 Hz), 7.4 ms (OGSE 25 Hz), 20 ms (PGSE), and 40 ms (PGSE). Eigenvalues and FA were compared in the corpus callosum body, splenium and genu, and the corticospinal, cingulum, inferior fronto‐occipital, superior and inferior longitudinal fasciculi using tractography, and the thalamus and putamen using region‐of‐interest.

Results

Relative to 40 ms, the 4.1 ms diffusion time led to significant increases in DTI eigenvalues in seven white matter tracts (6% to 20% parallel, 13% to 40% perpendicular) and both deep gray matter regions (16% parallel, 18% to 26% perpendicular), and reductions of FA (−9% to −12%) in four tracts.

Conclusion

DTI eigenvalues and FA depend on diffusion time in both white and gray matter in the human brain. The ability to target different length scales by means of the diffusion time may improve sensitivity to changes in tissue microstructure associated with pathology. Magn Reson Med 72:726–736, 2014. © 2013 Wiley Periodicals, Inc.
Improve myocardial T1 measurement in rats with a new regression model: Application to myocardial infarction and beyond
Authors: Zhang Haosen , Ye Qing , Zheng Jie , Schelbert Erik B. , Hitchens T. Kevin , Ho Chien
Published: October 2013

Purpose

To improve myocardial and blood T1 measurements with a multi‐variable T1 fitting model specifically modified for a segmented multi‐shot FLASH sequence.

Methods

The proposed method was first evaluated in a series of phantoms simulating realistic tissues, and then in healthy rats (n = 8) and rats with acute myocardial infarction (MI) induced by coronary artery ligation (n = 8).

Results

By taking into account the saturation effect caused by sampling α‐train pulses, and the longitudinal magnetization recovery between readouts, our model provided more accurate T1 estimate than the conventional three‐parameter fit in phantoms under realistic gating procedures (error of −0.42 ± 1.73% versus −3.40 ± 1.46%, respectively, when using the measured inversion efficiency, β). The baseline myocardial T1 values in healthy rats was 1636.3 ± 23.4 ms at 7 Tesla. One day postligation, the T1 values in the remote and proximal myocardial areas were 1637.5 ± 62.6 ms and 1740.3 ± 70.5 ms, respectively. In rats with acute MI, regional differences in myocardial T1 values were observed both before and after the administration of gadolinium.

Conclusion

The proposed method has improved T1 estimate as validated in phantoms and could advance applications in rodents using quantitative myocardial T1 mapping. Magn Reson Med 72:737–748, 2014. © 2013 Wiley Periodicals, Inc.
Successful treatment of severe myasthenia gravis developed after allogeneic hematopoietic stem cell transplantation with plasma exchange and rituximab
Authors: Unal Sule , Sag Erdal , Kuskonmaz Baris , Kesici Selman , Bayrakci Benan , Ayvaz Deniz C. , Tezcan Ilhan , Yalnızoglu Dilek , Uckan Duygu
Published: October 2013

Myasthenia gravis is among the rare complications after allogeneic hematopoietic stem cell transplantation and is usually associated with chronic GVHD. Herein, we report a 2‐year and 10 months of age female with Griscelli syndrome, who developed severe myasthenia gravis at post‐transplant +22nd month and required respiratory support with mechanical ventilation. She was unresponsive to cyclosporine A, methylprednisolone, intravenous immunoglobulin, and mycophenolate mofetil and the symptoms could only be controlled after plasma exchange and subsequent use of rituximab, in addition to cyclosporine A and mycophenolate mofetil maintenance. She is currently asymptomatic on the 6th month of follow‐up. Pediatr Blood Cancer 2014;61:928–930. © 2013 Wiley Periodicals, Inc.
Natural killer cell therapy and aerosol interleukin‐2 for the treatment of osteosarcoma lung metastasis
Authors: Guma Sergei R. , Lee Dean A. , Yu Ling , Gordon Nancy , Hughes Dennis , Stewart John , Wang Wei Lien , Kleinerman Eugenie S.
Published: October 2013

Background

Survival of patients with osteosarcoma lung metastases has not improved in 20 years. We evaluated the efficacy of combining natural killer (NK) cells with aerosol interleukin‐2 (IL‐2) to achieve organ‐specific NK cell migration and expansion in the metastatic organ, and to decrease toxicity associated with systemic IL‐2.

Procedure

Five human osteosarcoma cell lines and 103 patient samples (47 primary and 56 metastatic) were analyzed for NKG2D ligand (NKG2DL) expression. Therapeutic efficacy of aerosol IL‐2 + NK cells was evaluated in vivo compared with aerosol IL‐2 alone and NK cells without aerosol IL‐2.

Results

Osteosarcoma cell lines and patient samples expressed various levels of NKG2DL. NK‐mediated killing was NKG2DL‐dependent and correlated with expression levels. Aerosol IL‐2 increased NK cell numbers in the lung and within metastatic nodules but not in other organs. Therapeutic efficacy, as judged by tumor number, size, and quantification of apoptosis, was also increased compared with NK cells or aerosol IL‐2 alone. There were no IL‐2‐associated systemic toxicities.

Conclusion

Aerosol IL‐2 augmented the efficacy of NK cell therapy against osteosarcoma lung metastasis, without inducing systemic toxicity. Our data suggest that lung‐targeted IL‐2 delivery circumvents toxicities induced by systemic administration. Combining aerosol IL‐2 with NK cell infusions, may be a potential new therapeutic approach for patients with osteosarcoma lung metastasis. Pediatr Blood Cancer 2014;61:618–626. © 2013 Wiley Periodicals, Inc.
Myoepithelial carcinoma treatment in children: A report from the TREP project
Authors: Bisogno Gianni , Tagarelli Arianna , Schiavetti Amalia , Scarzello Giovanni , Ferrari Andrea , Cecchetto Giovanni , Alaggio Rita
Published: October 2013

Background

Myoepithelial carcinoma (MC) of soft tissues is an aggressive tumor that rarely affects children, for whom no established treatment protocols exist. As part of the TREP (Tumori Rari in Età Pediatrica) project – an Italian network dedicated to children and adolescents with very rare tumors – we present a series of patients with MC, who were treated homogeneously and achieved a satisfactory outcome.

Procedure

From 2005 to 2012, seven patients (age 0.5–9.2 years) with a diagnosis of MC were registered in the TREP study. After one patient treated with ifosfamide, cisplatin, and etoposide showed tumor shrinkage and experienced long‐term disease remission, all subsequent patients were treated with the same chemotherapy regimen. All patients also received radiotherapy.

Results

Initial surgical management involved a biopsy in three cases and tumor resection in 4. Response to initial chemotherapy was evaluable in four patients: two had a partial remission, one a minor response and one stable disease. Four patients received external‐beam radiotherapy and three had brachytherapy. Overall, six patients are alive in first complete remission with a median follow‐up of 2.5 years (0.9–5.1 years).

Conclusions

Though our experience is limited to a small number of patients, our treatment strategy for patients with MC is appears clinically useful and demonstrates how cooperation within the TREP project has enabled enough data to be collected to propose treatment recommendations for pediatric patients with this very rare tumor. Pediatr Blood Cancer 2014;61:643–646. © 2013 Wiley Periodicals, Inc.