bluuebunny/crossref_metadata_2025 huggingface dataset:
Microstructural brain abnormalities of children of idiopathic generalized epilepsy with generalized tonic‐clonic seizure: A voxel‐based diffusional kurtosis imaging study
Authors: Gao Junling , Feng Shi‐Ting , Wu Bangxian , Gong Nanjie , Lu Minhua , Wu Po‐Man , Wang He , He Xiaoming , Huang Bingsheng
Published: May 2014

The above article, published online on 3 May 2014 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor in Chief, and Wiley Periodicals, Inc. The retraction has been agreed due to errors in the results of the published article. The authors stated in the Methods section that ‘. . . only clusters with a false discovery rate (FDR)‐corrected P‐value less than 0.05 were included.’ However, it was subsequently discovered that the FDG‐correction had not been performed correctly. Had this been carried out in the right way, the difference between the case group and the control group in most of the presented regions would have been insignificant.

REFERENCE

1. Gao J, Feng S‐T, Wu B, Gong N, Lu M, Wu P‐M, Wang H, He X, and Huang B. Microstructural Brain Abnormalities of Children of Idiopathic Generalized Epilepsy With Generalized Tonic‐Clonic Seizure: A Voxel‐Based Diffusional Kurtosis Imaging Study J mag res. 2014 May 3. doi: 10.1002/jmri.24647 [epub ahead of print]
Testing the capability of a polynomial‐modified gaussian model in the description and simulation of chromatographic peaks of amlodipine and its impurity in ion‐interaction chromatography
Authors: Čolović Jelena , Vemić Ana , Kostić Nađa , Malenović Anđelija , Medenica Mirjana
Published: May 2014

In this paper, the capability of a polynomial‐modified Gaussian model to relate the peak shape of basic analytes, amlodipine, and its impurity A, with the change of chromatographic conditions was tested. For the accurate simulation of real chromatographic peaks the authors proposed the three‐step procedure based on indirect modeling of peak width at 10% of peak height (W0.1), individual values of left‐half width (A) and right‐half width (B), number of theoretical plates (N), and tailing factor (Tf). The values of retention factors corresponding to the peak beginning (kB), peak apex (kA), peak ending (kE), and peak heights (H0) of the analytes were directly modeled. Then, the investigated experimental domain was divided to acquire a grid of appropriate density, which allowed the subsequent calculation of W0.1, A, B, N, and Tf. On the basis of the predicted results for Tf and N, as well as the defined criteria for the simulation the following conditions were selected: 33% acetonitrile/67% aqueous phase (55 mM perchloric acid, pH 2.2) at 40°C column temperature. Perfect agreement between predicted and experimental values was obtained confirming the ability of polynomial modified Gaussian model and three‐step procedure to successfully simulate the real chromatograms in ion‐interaction chromatography.
Time to transplantation as a predictor of hepatocellular carcinoma recurrence after liver transplantation
Authors: Samoylova Mariya L. , Dodge Jennifer L. , Yao Francis Y. , Roberts John Paul
Published: May 2014

In the United States, there are significant geographic disparities in the time to transplantation for patients with hepatocellular carcinoma (HCC); it is possible that rapid transplantation contributes to higher rates of posttransplant HCC recurrence because there is insufficient time for the tumor biology to manifest. In this study, we compared HCC recurrence in rapid transplant patients and their slower transplant counterparts. We identified adult liver transplantation (LT) candidates in the Organ Procurement and Transplantation Network/United Network for Organ Sharing (UNOS) data set who were granted an initial exception for an HCC diagnosis between January 1, 2006 and September 30, 2010 and underwent transplantation in the same time window. Patients were followed until HCC recurrence, non–HCC-related death, or last follow-up. The cumulative incidence of HCC recurrence was compared for patients waiting ≤120 days and patients waiting >120 days from an HCC exception to LT. The association between the risk of posttransplant recurrence and the wait time was further evaluated via competing risks regression with the Fine and Gray model. For 5002 LT recipients with HCC, the median wait time from an exception to LT was 77 days, and it varied from 30 to 169 days by UNOS region. The cumulative incidence of posttransplant HCC recurrence was 3.3% [95% confidence interval (CI) = 2.8%-3.8%] and 5.6% (95% CI = 5.0%-6.3%) within 1 and 2 years, respectively. The rate of observed recurrence within 1 year of transplantation was significantly lower for patients waiting >120 days versus patients waiting ≤120 days (2.2% versus 3.9%, P = 0.002); however, the difference did not persist at 2 years (5.0% versus 5.9%, P = 0.09). After we accounted for clinical factors, the HCC recurrence risk was reduced by 40% for patients waiting >120 days (subhazard ratio = 0.6, P = 0.005). In conclusion, the risk of HCC recurrence within the first year after transplantation may be lessened by the institution of a mandatory waiting time after an exception is granted. Liver Transpl 20:937–944, 2014. © 2014 AASLD.
Boundary of Anosov dynamics and evolution equations for surfaces
Authors: Jane Dan , Ruggiero Rafael O.
Published: May 2014

We show that a compact surface of genus greater than one, without focal points and a finite number of bubbles (“good” shaped regions of positive curvature) is in the closure of Anosov metrics. Compact surfaces of nonpositive curvature and genus greater than one are in the closure of Anosov metrics, by Hamilton's work about the Ricci flow. We generalize this fact to the above surfaces without focal points admitting regions of positive curvature using a “magnetic” version of the Ricci flow, the so‐called Ricci Yang‐Mills flow.
Gallotannin is a DNA damaging compound that induces senescence independently of p53 and p21 in human colon cancer cells
Authors: Al‐Halabi Racha , Abou Merhi Raghida , Chakilam Saritha , El‐Baba Chirine , Hamade Eva , Di Fazio Pietro , Ocker Matthias , Schneider‐Stock Regine , Gali‐Muhtasib Hala
Published: May 2014

The plant secondary metabolite gallotannin (GT) is the simplest hydrolyzable tannin shown to have anti‐carcinogenic properties in several cell lines and to inhibit tumor development in different animal models. Here, we determined if GT induces senescence and DNA damage and investigated the involvement of p53 and p21 in this response. Using HCT116 human colon cancer cells wildtype for p53+/+/p21+/+ and null for p53+/+/p21−/− or p53−/−/p21+/+, we found that GT induces senescence independently of p21 and p53. GT was found to increase the production of reactive oxygen species (ROS) by altering the redox balance in the cell, mainly by reducing the levels of glutathione and superoxide dismutase (SOD). Using the key antioxidants N‐acetyl cysteine, dithiothreitol, SOD, and catalase, we showed that ROS were partially involved in the senescence response. Furthermore, GT‐induced cell cycle arrest in S‐phase in all HCT116 cell lines. At later time points, we noticed that p53 and p21 null cells escaped complete arrest and re‐entered cell cycle provoking higher rates of multinucleation. The senescence induction by GT was irreversible and was accompanied by significant DNA damage as evidenced by p‐H2AX staining. Our findings indicate that GT is an interesting anti colon cancer agent which warrants further study. © 2014 Wiley Periodicals, Inc.
Electrically induced torque decrease reflects more than muscle fatigue
Authors: Papaiordanidou Maria , Stevenot Jean‐Damien , Mustacchi Valerie , Vanoncini Michele , Martin Alain
Published: May 2014

The aim of the study was to compare the fatigue induced by different electrical stimulation (ES) protocols. The triceps surae muscle of 8 healthy subjects was fatigued with 4 protocols (30 Hz−500 μs, 30 Hz−1 ms, 100 Hz−1 ms, and 100 Hz−500 μs), composed of 60 trains (4 s on–6 s off), delivered at an intensity evoking 30% of maximal voluntary contraction (MVC). Fatigue was quantified by ES and MVC torque decreases. The amplitude of the twitch delivered at the intensity and pulse width used in each fatiguing protocol (twitch at Istim) was analyzed. All parameters decreased significantly after all protocols. The ES torque decrease correlated positively with the twitch decrease elicited at Istim only for the 30‐Hz protocols. Results show that, during the 100‐Hz protocols, phenomena not related to the fatigue of the solicited motor units may occur, including changes in the excitability threshold of the axonal terminal branches. Muscle Nerve 50: 604–606, 2014
General coupling extended multiscale FEM for elasto‐plastic consolidation analysis of heterogeneous saturated porous media
Authors: Zhang Hongwu , Lu Mengkai , Zheng Yonggang , Zhang Sheng
Published: May 2014

This paper presents a general coupling extended multiscale FEM (GCEMs) for solving the coupling problem of elasto‐plastic consolidation of heterogeneous saturated porous media. In the GCEMs, the numerical multiscale base functions for the solid skeleton and fluid phase of the coupling system are all constructed on the basis of the equivalent stiffness matrix of the unit cell, which not only contain the interaction between the solid and fluid phases but also consider the time effect. Furthermore, in order to improve the computational accuracy for two‐dimensional problems, a multi‐node coarse element strategy for the GCEMs is proposed, and a two‐scale iteration algorithm for the elasto‐plastic consolidation analysis is developed. Some one‐dimensional and two‐dimensional homogeneous and heterogeneous numerical examples are carried out to validate the proposed method through the comparison with the coupling multiscale FEM and standard FEM. Numerical results show that the newly developed GCEMs can almost preserve the same convergent property as the standard FEM and also possesses the advantages of high computational efficiency. In addition, the GCEMs can be easily applied to other coupling multifield and multiphase transient problems. Copyright © 2014 John Wiley & Sons, Ltd.
Image‐based simulation of urethral distensibility and flow resistance as a function of pelvic floor anatomy
Authors: Yao Franklin , Laudano Melissa A. , Seklehner Stephan , Chughtai Bilal , Lee Richard K.
Published: May 2014

Aims

The goal of this study is to develop an image‐based model of urethral distention and resistance in women with and without SUI.

Methods

A biomechanical vector force model was created to simulate the mechanical deformation of pelvic floor structures during cough and Valsalva in order to measure urethral distension and predict flow resistance patterns. Dynamic MRI images were used to create a spatial model to construct an accurate representation of tissue thickness and location, which was combined with tissue property values (MATLAB 2011a, MathWorks, Natick, MA). Spatial profiles were created to demonstrate the effects of hypermobility and tissue property variability on distensibility and flow resistance along the urethra. Sensitivity analyses were conducted to demonstrate the relationship between flow resistance and various tissue properties.

Results

The average distension for incontinent cases (3.8 mm) was significantly greater than that of continent cases (2.6 mm) (t = 3.3083, df = 8, P < 0.01), corresponding to a 70% drop in average resistance to urine flow. Sensitivity analyses demonstrated that the stiffness and contractility of the vagina and urethra had the greatest effect on continence.

Conclusions

We present a novel, 2‐dimensional biomechanical model of female stress urinary incontinence (SUI) that relates the effects of various factors such as tissue elasticity, pelvic floor structure, and muscle activation. A better understanding of the pathophysiology underlying SUI has potential implications for the creation of novel targeted treatments. Neurourol. Urodynam. 34:???–???, 2015. © 2014 Wiley Periodicals, Inc.
Rapidly derived colorectal cancer cultures recapitulate parental cancer characteristics and enable personalized therapeutic assays
Authors: Ashley Neil , Jones Matthew , Ouaret Djamila , Wilding Jenny , Bodmer Walter F
Published: May 2014

We have developed a simple procedure for deriving pure cultures of growing cancer cells from colorectal cancers, including material refrigerated overnight, for pathological characterization and cytotoxicity assays. Forty‐six cancers were processed and cultures set up under varying culture conditions. Use of a Rho kinase (ROCK1) inhibitor markedly increased culture survival, resulting in 80% of samples growing in culture for at least 1 month and beyond. Overnight refrigeration of samples before culture initiation had little effect on success rates, paving the way for cultures to be established for samples collected over wide geographical areas, such as those for clinical trials. Primary cultures demonstrated good correlation for differentiation markers compared to parent cancers, and were highly dynamic in 3D culture. In Matrigel, many colonies formed central lumens, indicating the presence of stem‐like cells. Viable colonies in these cultures recapitulated the in vivo generation of carcinoembryonic antigen (CEA)‐positive necrotic/apoptotic debris, much of which was derived from abnormal vacuolated dynamic ‘bubble cells’ that have not previously been described. Although bubble cells morphologically resembled signet ring cells, a rare cancer subtype, immunostaining suggested that they were most likely derived from terminally differentiated enterocytes. Micro‐assays showed that drug toxicity could be measured in these cultures within hours and with sensitivity down to a few hundred cells. Primary cultures derived by our method provide valid in vitro avatars for studying the pathology of cancers in vitro and are amenable to pre‐clinical drug testing, paving the way for personalized cancer treatment. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
CLASSROOM VICTIMIZATION: CONSEQUENCES FOR SOCIAL AND ACADEMIC ADJUSTMENT IN ELEMENTARY SCHOOL
Authors: Reuland Meg M. , Mikami Amori Yee
Published: May 2014

Peer victimization is a well‐established risk factor for children's adjustment, but it has rarely been studied as a feature of classroom climate. This study examines the consequences of classroom victimization for children's social and academic adjustment. Classroom victimization, social functioning, and academic adjustment were assessed in two subsamples taken from a full sample of 523 children nested in 28 classrooms, followed over the course of a school year. Results from a subsample of 213 students suggested that higher classroom levels of victimization predicted attenuated growth in children's reading achievement as well as greater stability of reading achievement over the course of the year. Results from a subsample of 490 children suggested that lower levels of classroom victimization predicted reduced stability of peer social preference and mitigated the trajectory between children's externalizing behavior and poor social preference. Implications for prevention of and interventions targeting peer victimization are discussed.
A Detailed Description of the Chemistry of Thiol Supporting Plasma Polymer Films
Authors: Thiry Damien , Francq Remy , Cossement Damien , Guillaume Maxime , Cornil Jérôme , Snyders Rony
Published: May 2014

In this work, the plasma polymerization of propanethiol is investigated with the aim to control the thiol density [SH] in the coatings. The results reveal a nearly constant evolution of [SH] regarding the mean power dissipated in the discharge. This peculiar behavior is explained considering (i) mass spectrometry data revealing a similar relative concentration of condensable SH‐bearing species in the plasma and (ii) similar energetic conditions at the growing film/plasma interface. Finally, it is observed that the low 〈P〉 synthesized films are not chemically stable in solution likely due to the release of H2S molecules trapped in the material network. The whole set of our data allows to provide a deeper understanding of the growth mechanism of propanethiol plasma polymer, essential for future development.
Phase transitions in lipid vesicles detected by a complementary set of methods: heat‐transfer measurements, adiabatic scanning calorimetry, and dissipation‐mode quartz crystal microbalance
Authors: Losada‐Pérez P. , Jiménez‐Monroy K. L. , van Grinsven B. , Leys J. , Janssens S. D. , Peeters M. , Glorieux C. , Thoen J. , Haenen K. , De Ceuninck W. , Wagner P.
Published: May 2014

We report on the use of the heat transfer method, a novel surface‐sensitive technique based on heat transfer through solid–liquid interfaces, to detect phase transitions of model lipid membranes. We selected the lipid DPPC because of its rich phase behavior in an experimentally accessible temperature range. The vesicles were adsorbed on nanocrystalline diamond films, known as a versatile platform material for biosensing with outstanding heat‐conduction properties. Complementary Peltier‐element‐based adiabatic scanning calorimetry (pASC) and quartz crystal microbalance with dissipation monitoring (QCM‐D) measurements were carried out to monitor the phase transitions in multilamellar and small unilamellar vesicles, respectively. The heat‐transfer measurements revealed reversible jumps upon heating and cooling in the thermal resistance in the vicinity of the expected transition temperature and they agree qualitatively with molecular simulations of the thermal conductivity across a lipid bilayer. The results show the capability of the heat transfer method to detect the main phase transition in DPPC, opening new perspectives for the study of more complex lipid systems and different solid platforms. This work confirms QCM‐D as a useful tool for the assessment of the structural changes upon the phase conversion and shows the capability of pASC to provide high‐resolution thermodynamic information on biophysical systems.

Temperature profile of the heat transfer resistance Rth during the main phase transition of a DPPC supported vesicle layer adsorbed on a hydrogen‐terminated nanocrystalline diamond substrate. The arrows indicate the sense of the run: heating (red solid line) and cooling (blue solid line).
Prophylactic and Therapeutic Effects of Acanthopanax senticosus Harms Extract on Murine Collagen‐induced Arthritis
Authors: Takahashi Yusuke , Tanaka Maki , Murai Ryosei , Kuribayashi Kageaki , Kobayashi Daisuke , Yanagihara Nozomi , Watanabe Naoki
Published: May 2014

Evidences are accumulating that extract of Acanthopanax senticosus Harms (ASH; syn Eleutherococcus senticosus [Rupr. & Maxim.] Maxim), a shrub native to Northeastern Asia, has antiinflammatory effects. In this study, we examined prophylactic and therapeutic effects of ASH extract (ASHE) on rheumatoid arthritis using collagen‐induced arthritis (CIA) mouse model. Acanthopanax senticosus Harms extract was administered before the onset of arthritis in the prophylaxis model. In the therapeutic model, ASHE was administered after the onset of arthritis with or without anti‐TNF‐α antibody. The ASHE treatment showed efficacy before onset of CIA but there was no effect after CIA was established. The ASHE treatment delayed the onset and decreased severity of CIA. In vitro examinations showed that ASHE is an antioxidant and that ASHE suppresses TNF‐α and interleukin‐6 production in human peripheral blood mononuclear cells. The combination therapy with ASHE and anti‐TNF‐α antibody reduced the severity of arthritis compared with anti‐TNF‐α antibody alone. The present study shows that ASHE has prophylactic effect against CIA and support therapeutic effect of anti‐TNF‐α antibody. © 2014 The Authors. Phytotherapy Research published by John Wiley & Sons Ltd.
Temporal Variations in Dissolved Oxygen Concentrations Observed in a Shallow Floodplain Aquifer
Authors: Schilling K. E. , Jacobson P. J.
Published: May 2014

Dissolved oxygen (DO) concentrations play an important role in many groundwater biogeochemial processes, yet assessments of temporal variations are lacking. In this study, we examined daily DO concentrations using a continuously‐reading optical DO probe in a shallow floodplain setting in Iowa to (i) quantify fluctuations across two growing seasons; (ii) examine hydrologic controls on DO values; and (iii) model daily DO concentrations using easily measured variables. DO concentrations exhibited both rapid and long‐term changes in concentrations over time, rapidly increasing and decreasing more than 1 mg/l in response to precipitation recharge and stream stage increase over the span of several hours and days. On 40% of the monitoring days in this study, DO concentrations increased, on average, 0.2–0.4 mg/l from one day to the next. DO concentrations decreased approximately 5–6 mg/l from spring through late summer and fall, likely owing to microbial and root respiration. Daily DO concentrations were successfully modelled using a combination of hydrologic (groundwater level and river stage) and temperature variables (r2 > 0.7). Improved understanding of temporal controls on groundwater DO patterns is needed to help clarify the dynamics of many biogeochemical processes. Copyright © 2014 John Wiley & Sons, Ltd.
Exploring and inferring user–user pseudo‐friendship for sentiment analysis with heterogeneous networks
Authors: Deng Hongbo , Han Jiawei , Li Hao , Ji Heng , Wang Hongning , Lu Yue
Published: May 2014

With the development of social media and social networks, user‐generated content, such as forums, blogs and comments, are not only getting richer, but also ubiquitously interconnected with many other objects and entities, forming a heterogeneous information network between them. Sentiment analysis on such kinds of data can no longer ignore the information network, since it carries a lot of rich and valuable information, explicitly or implicitly, where some of them can be observed while others are not. However, most existing methods may heavily rely on the observed user–user friendship or similarity between objects, and can only handle a subgraph associated with a single topic. None of them takes into account the hidden and implicit dissimilarity, opposite opinions, and foe relationship. In this paper, we propose a novel information network‐based framework which can infer hidden similarity and dissimilarity between users by exploring similar and opposite opinions, so as to improve post‐level and user‐level sentiment classification at the same time. More specifically, we develop a new meta path‐based measure for inferring pseudo‐friendship as well as dissimilarity between users, and propose a semi‐supervised refining model by encoding similarity and dissimilarity from both user‐level and post‐level relations. We extensively evaluate the proposed approach and compare with several state‐of‐the‐art techniques on two real‐world forum datasets. Experimental results show that our proposed model with 10.5% labeled samples can achieve better performance than a traditional supervised model trained on 61.7% data samples.
Nano‐Dissection and Sequencing of DNA at Single Sub‐Nuclear Structures
Authors: Chen Brandon K. , Anchel David , Gong Zheng , Cotton Rachel , Li Ren , Sun Yu , Bazett‐Jones David P
Published: May 2014

The relative positioning of gene loci within a mammalian nucleus is non‐random and plays a role in gene regulation. Some sub‐nuclear structures may represent “hubs” that bring specific genetic loci into close proximity where co‐regulatory mechanisms can operate. The identification of loci in proximity to a shared sub‐nuclear structure can provide insights into the function of the associated structure, and reveal relationships between the loci sharing a common association. A technique is introduced based on the nano‐dissection of DNA from thin sections of cells by high‐precision nano‐tools operated inside a scanning electron microscope. The ability to dissect and identify gene loci occupying a shared site at a single sub‐nuclear structure is demonstrated here for the first time. The technique is applied to the nano‐dissection of DNA in vicinity of a single promyelocytic leukemia nuclear body (PML NB), and reveals novel loci from several chromosomes that are confirmed to associate at PML NBs with statistical significance in a cell population. Furthermore, it is demonstrated that pairs of loci from different chromosomes congregate at the same nuclear body. It is proposed that this technique is the first that allows the de novo determination of gene loci associations with single nuclear sub‐structures.
Learning about application software by studying processes
Authors: Osterweil Leon J.
Published: May 2014

In earlier work, it has been suggested that processes and applications seem to share many important characteristics and seem to be amenable to similar approaches of modeling, definition, and analysis. In most of this previous work, approaches and technologies for developing applications have been applied to the development of processes, largely with positive results. This paper suggests the opposite, namely that approaches and technologies for developing processes seem likewise to be applicable to developing applications. As an example, this paper notes that resource specification, allocation, and management are central issues in the development of many processes, and suggests that although these capabilities seem to be important for growing classes of application software, the ability to support them seems curiously neglected. The paper also notes that management of rework is a central issue of virtually all creative activities. This is evidenced by the observation that facilities for supporting rework are prominent features in so many creative domains. Accordingly, the paper suggests an analogous need for facilities for supporting rework in application software as well, especially in application software aimed at supporting human creativity. The paper concludes by noting that both application and process software technologies grow through consideration of the relevance of technologies developed for one to the other. This in turn should lead to a clearer understanding of the essence of what they have in common, leading to conjectures about the nature of a more abstract class of entities, that we refer to simply as software. Copyright © 2014 John Wiley & Sons, Ltd.
Study on Mathematical Modeling of Combined Top and Bottom Blowing VOD Refining Process of Stainless Steel
Authors: Wei Ji‐He , Li Yi
Published: May 2014

A mathematical model for the combined top and bottom blowing VOD refining of stainless steel has been proposed. It is essentially based on the assumptions made for the AOD process of stainless steel under the conditions of combined side and top blowing in our previous work, but considering the effects of reduced ambient pressure and the degassing in the refining. The influence of the operational factors, the non‐isothermal conditions and others has all been considered. The model has been applied to 20 heats of 409L‐grade ferritic stainless steel refining in a 120 t VOD vessel. The results show that the changes in the composition and temperature of the steel during the whole refining process with the time can be precisely predicted by the model. The critical carbon concentration (after which the decarburization alters to be limited by the mass transfer of carbon in molten steel) for the combined blowing of 409L‐grade steel in this work is in the range of 0.119 to 0.182 mass%, in agreement essentially with that of the oxygen top blowing. The influences of the related factors on the refining effectiveness and the optimization of blowing technology have been examined from the model predictions. The model can offer useful information for determining and optimizing the technology of the VOD refining of stainless steel, and controlling the process in real time and online.
Concerned with the unprivileged: user programs in kernel refinement
Authors: Daum Matthias , Billing Nelson , Klein Gerwin
Published: May 2014

It is a great verification challenge to prove properties of complete computer systems on the source code level. The L4.verified project achieved a major step towards this goal by mechanising a proof of functional correctness of the seL4 kernel. They expressed correctness in terms of data refinement with a coarse-grained specification of the kernel’s execution environment. In this paper, we strengthen the original correctness theorem in two ways. First, we convert the previous abstraction relations into projection functions from concrete to abstract states. Second, we revisit the specification of the kernel’s execution environment: we introduce the notion of virtual memory based on the kernel data structures, we distinguish individual user programs that run on top of the kernel and we restrict the memory access of each of these programs to its virtual memory. Through our work, properties like the separation of user programs gain meaning. This paves the way for proving security properties like non-interference of user programs. Furthermore, our extension of L4.verified’s proof facilitates the verification of properties about complete software systems based on the seL4 kernel. Besides the seL4-specific results, we report on our work from an engineering perspective to exemplify general challenges that similar projects are likely to encounter. Moreover, we point out the advantages of using projection functions in L4.verified’s verification approach and for stepwise refinement in general.
Assessment of low-dose cisplatin as a model of nausea and emesis in beagle dogs, potential for repeated administration
Authors: Kenward Hannah , Pelligand Ludovic , Elliott Jonathan
Published: May 2014

Cisplatin is a highly emetogenic cancer chemotherapy agent, which is often used to induce nausea and emesis in animal models. The cytotoxic properties of cisplatin also cause adverse events that negatively impact on animal welfare preventing repeated administration of cisplatin. In this study, we assessed whether a low (subclinical) dose of cisplatin could be utilized as a model of nausea and emesis in the dog while decreasing the severity of adverse events to allow repeated administration. The emetic, nausea-like behavior and potential biomarker response to both the clinical dose (70 mg/m2) and low dose (15 mg/m2) of cisplatin was assessed. Plasma creatinine concentrations and granulocyte counts were used to assess adverse effects on the kidneys and bone marrow, respectively. Nausea-like behavior and emesis was induced by both doses of cisplatin, but the latency to onset was greater in the low-dose group. No significant change in plasma creatinine was detected for either dose groups. Granulocytes were significantly reduced compared with baseline (P = 0.000) following the clinical, but not the low-dose cisplatin group. Tolerability of repeated administration was assessed with 4 administrations of an 18 mg/m2dose cisplatin. Plasma creatinine did not change significantly. Cumulative effects on the granulocytes occurred, they were significantly decreased (P = 0.03) from baseline at 3 weeks following cisplatin for the 4th administration only. Our results suggest that subclinical doses (15 and 18 mg/m2) of cisplatin induce nausea-like behavior and emesis but have reduced adverse effects compared with the clinical dose allowing for repeated administration in crossover studies.
Prediction of Permanent Hypoparathyroidism after Total Thyroidectomy
Authors: Almquist M. , Hallgrimsson P. , Nordenström E. , Bergenfelz A.
Published: May 2014

Background

Hypoparathyroidism is a common complication with thyroid surgery. The ability to predict a high risk of permanent hypoparathyroidism is important for individual prognosis and follow‐up.

Methods

Permanent hypoparathyroidism, defined as continuing need for vitamin D medication at 1‐year post‐operatively, was investigated in patients after total thyroidectomy. Blood levels of calcium and parathyroid hormone (PTH) were measured intra‐operatively, the day after surgery and at 1 month post‐operatively. Logistic regression analysis was performed to investigate the risk of vitamin D treatment at last follow‐up, calculated as odds ratios (ORs) with 95 % confidence intervals (CIs). Patients were followed until cessation of vitamin D and/or calcium medication, until death, loss to follow‐up, or end of follow‐up, whichever came first.

Results

A total of 519 patients were included. The median (range) follow‐up in patients unable to cease vitamin D was 2.7 (1.2–10.3) years. The rate of permanent hypoparathyroidism was 10/519, 1.9 %. Parathyroid auto‐transplantation was performed in 90/519 (17.3 %) patients. None of these developed permanent hypoparathyroidism, nor did any patient with normal PTH day 1 (>1.6 pmol/l or 15 pg/ml). The adjusted risk (OR, 95 % CI) for permanent hypoparathyroidism for log PTH on day 1 was 0.25 (0.13–0.50). In patients not auto‐transplanted and with unmeasurable PTH day 1 (<0.7 pmol/l or 6.6 pg/ml), 8/42 (19.2 %) developed permanent hypoparathyroidism.

Conclusions

Auto‐transplantation protects against permanent hypoparathyroidism, whereas low PTH day 1 is associated with high risk.
Synergistic effects of primates and dung beetles on soil seed accumulation in snow regions
Authors: Enari Hiroto , Sakamaki‐Enari Haruka
Published: May 2014

This study aimed to reveal the soil seed accumulation processes for endozoochorous plants in the heavy‐snowfall forests of Japan, where seed dispersal agents are few when compared to tropical forests. We assessed (1) primary seed dispersal by Japanese macaques (Macaca fuscata) by identifying dispersed seeds found in their feces, and (2) secondary seed dispersal by dung beetles by using beads (as seeds mimics) of different sizes, to quantify the frequency of seed burial and burial depths. We studied this diplochorous system in different forest types (undisturbed beech forest, conifer plantation, and secondary beech‐oak forest) and during the spring and summer seasons. The key findings were as follows: (1) macaques dispersed the seeds of 11 and 14 plant species during spring and summer, respectively; (2) seeds dispersed by macaques in the spring were smaller and twice as abundant than those dispersed in the summer; (3) although no differences were observed in the amount of beads buried by beetles between seasons, all bead sizes tended to be buried in deeper soil layers in the spring than in the summer; and (4) the seed supply to the soil in undisturbed beech forest and conifer plantation was greater than the one in secondary beech‐oak forest. Similar to what has been observed in tropical forests, seeds defecated by frugivorous mammals can be successfully incorporated into the underground soil seed bank through a diplochorous macaque‐beetle system in temperate forests of deep snow regions.
Practical Aspects of Risk Assessment in Gastrointestinal Stromal Tumors
Authors: Jones R. L.
Published: May 2014

Introduction

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract, which are characterized in the majority of cases by activating mutations in KIT and platelet-derived growth factor receptor alpha (PDGFRA). The introduction of tyrosine kinase inhibitors has revolutionized the management of patients with metastatic GIST. However, complete surgical resection remains the mainstay of management for those with localized disease. Recently, three large trials have confirmed the benefit of adjuvant imatinib therapy in patients who were at high risk of recurrence following complete resection. In this setting, it is critical that oncologists understand the various GIST risk assessment criteria and be able to apply these methods to accurately assess the risk of recurrence and the need for adjuvant imatinib therapy.

Purpose

The aim of this review is to outline the risk stratification systems currently available to oncologists who are treating patients with GIST, so they can be optimally applied for clinical decision-making.
Identification of a novel insect neuropeptide, CNMa and its receptor
Authors: Jung Sung-Hwan , Lee Jae-Hyuk , Chae Hyo-Seok , Seong Jae Young , Park Yoonseong , Park Zee-Yong , Kim Young-Joon
Published: May 2014

To identify ligands for orphan GPCRs, we searched novel neuropeptide genes in the Drosophila melanogaster genome. Here, we describe CNMa, a novel cyclic neuropeptide that is a highly potent and selective agonist for the orphan GPCR, CG33696 (CNMaR). Phylogenetic analysis revealed that arthropod species have two paralogous CNMaRs, but many taxa retain only one. Drosophila CNMa potently activates CNMaR‐2 from Apis mellifera, suggesting both receptors are functional. Although CNMa is conserved in most arthropods, Lepidoptera lack the CNMa gene. However, they retain the CNMaR gene. Bombyx CNMaR showed low sensitivity to Drosophila CNMa, hinting toward the existence of additional CNMaR ligand(s).
A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer's disease
Authors: Jessen Frank , Amariglio Rebecca E. , van Boxtel Martin , Breteler Monique , Ceccaldi Mathieu , Chételat Gaël , Dubois Bruno , Dufouil Carole , Ellis Kathryn A. , van der Flier Wiesje M. , Glodzik Lidia , van Harten Argonde C. , de Leon Mony J. , McHugh Pauline , Mielke Michelle M. , Molinuevo Jose Luis , Mosconi Lisa , Osorio Ricardo S. , Perrotin Audrey , Petersen Ronald C. , Rabin Laura A. , Rami Lorena , Reisberg Barry , Rentz Dorene M. , Sachdev Perminder S. , de la Sayette Vincent , Saykin Andrew J. , Scheltens Philip , Shulman Melanie B. , Slavin Melissa J. , Sperling Reisa A. , Stewart Robert , Uspenskaya Olga , Vellas Bruno , Visser Pieter Jelle , Wagner Michael ,   Subjective Cognitive Decline Initiative (SCD‐I) Working Group
Published: May 2014

There is increasing evidence that subjective cognitive decline (SCD) in individuals with unimpaired performance on cognitive tests may represent the first symptomatic manifestation of Alzheimer's disease (AD). The research on SCD in early AD, however, is limited by the absence of common standards. The working group of the Subjective Cognitive Decline Initiative (SCD‐I) addressed this deficiency by reaching consensus on terminology and on a conceptual framework for research on SCD in AD. In this publication, research criteria for SCD in pre‐mild cognitive impairment (MCI) are presented. In addition, a list of core features proposed for reporting in SCD studies is provided, which will enable comparability of research across different settings. Finally, a set of features is presented, which in accordance with current knowledge, increases the likelihood of the presence of preclinical AD in individuals with SCD. This list is referred to as SCD plus.
Clinical utility of cerebrospinal fluid biomarkers in the diagnosis of early Alzheimer's disease
Authors: Blennow Kaj , Dubois Bruno , Fagan Anne M. , Lewczuk Piotr , de Leon Mony J. , Hampel Harald
Published: May 2014

Several potential disease‐modifying drugs for Alzheimer's disease (AD) have failed to show any effect on disease progression in clinical trials, conceivably because the AD subjects are already too advanced to derive clinical benefit from treatment and because diagnosis based on clinical criteria alone introduces a high misdiagnosis rate. Thus, well‐validated biomarkers for early detection and accurate diagnosis are crucial. Low cerebrospinal fluid (CSF) concentrations of the amyloid‐β (Aβ1‐42) peptide, in combination with high total tau and phosphorylated tau, are sensitive and specific biomarkers highly predictive of progression to AD dementia in patients with mild cognitive impairment. However, interlaboratory variations in the results seen with currently available immunoassays are of concern. Recent worldwide standardization efforts and quality control programs include standard operating procedures for both preanalytical (e.g., lumbar puncture and sample handling) and analytical (e.g., preparation of calibration curve) procedures. Efforts are also ongoing to develop highly reproducible assays on fully automated instruments. These global standardization and harmonization measures will provide the basis for the generalized international application of CSF biomarkers for both clinical trials and routine clinical diagnosis of AD.
Going beyond numbers: A typology of health professional mobility inside and outside the European Union
Authors: Glinos Irene A
Published: May 2014

In a context of current and forecasted global health workforce shortages, attention around health professional mobility is mounting as observers and policy makers recognise its role in supplying health systems with the workforce they dependent on to function, or depleting these systems of their doctors and nurses. The paper proposes a typology of health professional mobility composed of six types of mobile health professionals and three types of borders. The framework draws attention to the individual's decision to migrate and to the role laws and borders play as determinants for mobility opportunities. In doing so, the typology is able to identify which types of mobile health professionals are likely to escape data collection, to highlight the distinction between free mobility within the EU and migration outside the EU's external borders, and to act as tool for designing policies adapted to the diversity of health professional mobility.
Bedeutung der allergologischen Abklärung bei Asthma und COPD
Authors: Schneider Spence Judith A. , Bircher Andreas J. , Scherer Hofmeier Kathrin
Published: May 2014

Während eine allergologische Abklärung im Work-Up eines Asthma bronchiale inbegriffen sein sollte, wird die chronisch obstruktive Pneumopathie nicht spontan mit einer atopischen Diathese in Zusammenhang gebracht. Anamnese, Klinik, das Vorhandensein weiterer atopischer Krankheiten sowie Prickteste und die serologische Messung von spezifischen IgE-Antikörpern geben Hinweise auf eine allergische Genese einer akuten oder chronischen Lungenkrankheit. Der Stickoxidwert in der Ausatemluft (FeNO-Messung) kann durch die Infiltration von Eosinophilen in die Bronchialwand beim allergischen Phänotyp des Asthma bronchiale erhöht sein (TH2-gewichteter Phänotyp). Eine Abhängigkeit der Beschwerden vom Arbeitsplatz muss evaluiert werden. Neben dem allergischen Typ des Asthma bronchiale soll auch an eine Aspirin-exacerbated-respiratory disease (AERD) gedacht werden. Aufgrund der überlappenden pathophysiologischen Grundlagen und der Symptomatik zwischen Asthma bronchiale und der chronisch obstruktiven Pneumopathie ist die Zuweisung zum Allergologen allenfalls auch bei einem COPD-Patienten indiziert.
Management von Exazerbationen in Asthma und COPD
Authors: Leuppi Jörg D. , Ott Sebastian R.
Published: May 2014

Asthma bronchiale und chronisch obstruktive Pneumopathie (COPD) sind chronische Atemwegserkrankungen mit einer hohen weltweiten Prävalenz. Beide Krankheiten können akut exazerbieren und dadurch Patienten in eine lebensbedrohliche Situation bringen. Das Management einer akuten Exazerbation fängt mit der akuten Situation an, hört aber erst nach sorgfältiger Überprüfung und Optimierung des Langzeitmanagements auf. Das Ziel ist, zukünftige Exazerbationen möglichst zu vermeiden, da die Exazerbation-Frequenz bei beiden Krankheiten stark mit der Langzeitprognose assoziiert ist. Neue Daten konnten zeigen, dass eine kürzere Behandlungsdauer mit systemischen Kortikosteroiden (5 Tage) bei einer akuten Exazerbation einer COPD die gleiche Erfolgschancen hat in den darauffolgenden 6 Monaten eine erneute Exazerbation zu verhindern wie eine Behandlungsdauer von 14 Tagen. Ebenfalls wird der gezielter Einsatz von Antibiotika in diesem Review diskutiert.
The maturation of antibody technology for the HIV epidemic
Authors: Winnall Wendy R , Beasley Matthew D , Center Rob J , Parsons Matthew S , Kiefel Ben R , Kent Stephen J
Published: May 2014

Antibodies are one of our most useful biological tools. Indeed, improvements in antibody‐based technologies have ushered in a new era of antibody‐based therapeutics, research and diagnostic tools. Although improved technologies have led to the development of therapeutic antibodies for treatment of malignancies and inflammatory conditions, the use of advanced antibody technology in the therapy of viral infections is in its infancy. Non‐human primate studies have demonstrated that antibodies against the HIV envelope can both prevent viral infection and control viremia. Despite the obvious potential of antibody therapies against HIV, there remain limitations in production and purification capacity that require further research. Recent advances in recombinant antibody technology have led to the development of a range of novel antibody fragments, such as single‐domain nanobodies and bispecific antibodies, that are capable of targeting cancer cells to cytotoxic T cells. Novel antibody production techniques have also been designed, allowing antibodies to be obtained from non‐mammalian cells, bovine colostrum and the periplasm and cytoplasm of bacteria. These advances may allow large‐scale production of HIV antibodies that are capable of protecting against HIV infection or serving as therapeutics that reduce the need for life‐long antiretroviral treatment. This review summarises recent advances in antibody‐based technologies and discusses the possibilities and challenges of using these advances to design prophylactics and therapeutics against HIV.
Nap1 stimulates homologous recombination by RAD51 and RAD54 in higher-ordered chromatin containing histone H1
Authors: Machida Shinichi , Takaku Motoki , Ikura Masae , Sun Jiying , Suzuki Hidekazu , Kobayashi Wataru , Kinomura Aiko , Osakabe Akihisa , Tachiwana Hiroaki , Horikoshi Yasunori , Fukuto Atsuhiko , Matsuda Ryo , Ura Kiyoe , Tashiro Satoshi , Ikura Tsuyoshi , Kurumizaka Hitoshi
Published: May 2014

Homologous recombination plays essential roles in mitotic DNA double strand break (DSB) repair and meiotic genetic recombination. In eukaryotes, RAD51 promotes the central homologous-pairing step during homologous recombination, but is not sufficient to overcome the reaction barrier imposed by nucleosomes. RAD54, a member of the ATP-dependent nucleosome remodeling factor family, is required to promote the RAD51-mediated homologous pairing in nucleosomal DNA. In higher eukaryotes, most nucleosomes form higher-ordered chromatin containing the linker histone H1. However, the mechanism by which RAD51/RAD54-mediated homologous pairing occurs in higher-ordered chromatin has not been elucidated. In this study, we found that a histone chaperone, Nap1, accumulates on DSB sites in human cells and DSB repair is substantially decreased in Nap1-knockdown cells. We determined that Nap1 binds to RAD54, enhances the RAD54-mediated nucleosome remodeling by evicting histone H1 and eventually stimulates the RAD51-mediated homologous pairing in higher-ordered chromatin containing histone H1.
Advantages, drawbacks and applications of mixed Ar–N2 sources in inductively coupled plasma-based techniques: an overview
Authors: Scheffler G. L. , Pozebon D.
Published: May 2014

This review deals with mixed gas Ar–N2 plasmas, highlighting advantages, limitations and applications of them in inductively coupled plasma optical emission spectrometry (ICP OES), inductively coupled plasma mass spectrometry (ICP-MS) and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) techniques, covering publications in the last three decades.
Electrocatalytic hydrogen generation by a trithiolato-bridged dimanganese hexacarbonyl anion with a turnover frequency exceeding 40 000 s−1
Authors: Hou Kaipeng , Poh Hwa Tiong , Fan Wai Yip
Published: May 2014

Electrocatalytic proton reduction based on a dimanganese hexacarbonyl anion.
Polymer-encapsulated organic nanoparticles for fluorescence and photoacoustic imaging
Authors: Li Kai , Liu Bin
Published: May 2014

In this Critical Review, we summarize the latest advances in the development of polymer encapsulated nanoparticles based on conjugated polymers and fluorogens with aggregation induced emission (AIE) characteristics, elucidate the importance of matrix selection and structure–property relationship of these nanoparticles and discuss their applications in fluorescence and photoacoustic imaging.