bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting outcomes following cognitive behaviour therapy in child anxiety disorders: the influence of genetic, demographic and clinical information
Authors: Hudson Jennifer L. , Lester Kathryn J. , Lewis Cathryn M. , Tropeano Maria , Creswell Cathy , Collier David A. , Cooper Peter , Lyneham Heidi J. , Morris Talia , Rapee Ronald M. , Roberts Susanna , Donald Jennifer A. , Eley Thalia C.
Published: June 2013

Background

Within a therapeutic gene by environment (G × E) framework, we recently demonstrated that variation in the Serotonin Transporter Promoter Polymorphism; 5HTTLPR and marker rs6330 in Nerve Growth Factor gene; NGF is associated with poorer outcomes following cognitive behaviour therapy (CBT) for child anxiety disorders. The aim of this study was to explore one potential means of extending the translational reach of G × E data in a way that may be clinically informative. We describe a ‘risk‐index’ approach combining genetic, demographic and clinical data and test its ability to predict diagnostic outcome following CBT in anxious children.

Method

DNA and clinical data were collected from 384 children with a primary anxiety disorder undergoing CBT. We tested our risk model in five cross‐validation training sets.

Results

In predicting treatment outcome, six variables had a minimum mean beta value of 0.5:5HTTLPR, NGF rs6330, gender, primary anxiety severity, comorbid mood disorder and comorbid externalising disorder. A risk index (range 0–8) constructed from these variables had moderate a predictive ability (AUC = .62–.69) in this study. Children scoring high on this index (5–8) were approximately three times as likely to retain their primary anxiety disorder at follow‐up as compared with those children scoring 2 or less.

Conclusion

Significant genetic, demographic and clinical predictors of outcome following CBT for anxiety‐disordered children were identified. Combining these predictors within a risk index could be used to identify which children are less likely to be diagnosis‐free following CBT alone and require longer or enhanced treatment. The ‘risk‐index’ approach represents one means of harnessing the translational potential of G × E data.
Immunohistochemical detection of p53 and p63 in oral squamous cell carcinoma, oral leukoplakia, and oral submucous fibrosis
Authors: Varun B.R. , Ranganathan K. , Rao Umadevi K. , Joshua Elizabeth
Published: June 2013

Aim

Oral squamous cell carcinoma (OSCC) may be preceded by potentially malignant disorders such as leukoplakia and oral submucous fibrosis (OSF). p63 in concert with p53 regulates cell proliferation and differentiation and may have a role in potentially malignant and malignant lesions of the oral cavity. The aim of the study was to evaluate and compare the expression of p53 and p63 proteins in OSCC, leukoplakia, and OSF by immunohistochemistry (IHC).

Methods

Tissue sections of OSCC (n = 20), leukoplakia (n = 20), OSF (n = 20) and normal oral mucosa (n = 10) were stained with p53 and p63 antibodies by IHC. Mean labeling index (LI) among the study groups were compared using the Kruskal–Wallis test.

Results

The mean LI of p53 for OSCC, leukoplakia, OSF, and normal mucosa were 56.9 ± 21.3, 37.6 ± 12.6, 34.6 ± 8.7 and 15.1 ± 9, while mean LI of p63 were 56.8 ± 19.6, 42.3 ± 10.5, 32.8 ± 12.1, and 26.4 ± 9.4. The mean LI of p53 and p63 were significantly higher in OSCC, leukoplakia and OSF compared to normal mucosa (P < 0.01; P < 0.01).

Conclusion

The significant increase in expression of p53 and p63 proteins in OSCC, leukoplakia, and OSF suggests their role as surrogate markers of malignant transformation.
Public Versus Private Provision of Public Goods
Authors: SLAVOV SITA NATARAJ
Published: June 2013

It is well known that public goods are underprovided in a static setting with voluntary contributions. Public provision—in a median voter framework with proportional taxation—generally exceeds private provision. This paper compares private and public provision of public goods in a dynamic setting. In a dynamic setting, voluntary donations can result in efficient provision. Also, majority‐rule solutions exist even when taxes are not proportional to income. At low discount factors, public provision tends to exceed private provision. As patience increases, however, private provision may exceed public provision. This occurs because many outcomes with a low level of public good provision—and potentially large targeted transfer payments to particular individuals—become sustainable under public provision. Under private provision, however, large targeted transfers are unsustainable. To finance the public good, private provision tends to result in benefit taxation, and public provision tends to result in progressive taxation.
ROBUST UTILITY MAXIMIZATION IN NONDOMINATED MODELS WITH 2BSDE: THE UNCERTAIN VOLATILITY MODEL
Authors: Matoussi Anis , Possamaï Dylan , Zhou Chao
Published: June 2013

The problem of robust utility maximization in an incomplete market with volatility uncertainty is considered, in the sense that the volatility of the market is only assumed to lie between two given bounds. The set of all possible models (probability measures) considered here is nondominated. We propose studying this problem in the framework of second‐order backward stochastic differential equations (2BSDEs for short) with quadratic growth generators. We show for exponential, power, and logarithmic utilities that the value function of the problem can be written as the initial value of a particular 2BSDE and prove existence of an optimal strategy. Finally, several examples which shed more light on the problem and its links with the classical utility maximization one are provided. In particular, we show that in some cases, the upper bound of the volatility interval plays a central role, exactly as in the option pricing problem with uncertain volatility models.
PORTFOLIO LIQUIDATION IN DARK POOLS IN CONTINUOUS TIME
Authors: Kratz Peter , Schöneborn Torsten
Published: June 2013

We consider an illiquid financial market where a risk averse investor has to liquidate a portfolio within a finite time horizon [0, T] and can trade continuously at a traditional exchange (the “primary venue”) and in a dark pool. At the primary venue, trading yields a linear price impact. In the dark pool, no price impact costs arise but order execution is uncertain, modeled by a multidimensional Poisson process. We characterize the costs of trading by a linear‐quadratic functional which incorporates both the price impact costs of trading at the primary exchange and the market risk of the position. The solution of the cost minimization problem is characterized by a matrix differential equation with singular boundary condition; by means of stochastic control theory, we provide a verification argument. If a single‐asset position is to be liquidated, the investor slowly trades out of her position at the primary venue, with the remainder being placed in the dark pool at any point in time. For multi‐asset liquidations this is generally not the case; for example, it can be optimal to oversize orders in the dark pool in order to turn a poorly balanced portfolio into a portfolio bearing less risk.
NO‐ARBITRAGE PRICING FOR DIVIDEND‐PAYING SECURITIES IN DISCRETE‐TIME MARKETS WITH TRANSACTION COSTS
Authors: Bielecki Tomasz R. , Cialenco Igor , Rodriguez Rodrigo
Published: June 2013

We prove a version of First Fundamental Theorem of Asset Pricing under transaction costs for discrete‐time markets with dividend‐paying securities. Specifically, we show that the no‐arbitrage condition under the efficient friction assumption is equivalent to the existence of a risk‐neutral measure. We derive dual representations for the superhedging ask and subhedging bid price processes of a contingent claim contract. Our results are illustrated with a vanilla credit default swap contract.
OPTIMAL HIGH‐FREQUENCY TRADING IN A PRO RATA MICROSTRUCTURE WITH PREDICTIVE INFORMATION
Authors: Guilbaud Fabien , Pham Huyên
Published: June 2013

We propose a framework to study optimal trading policies in a one‐tick pro rata limit order book, as typically arises in short‐term interest rate futures contracts. The high‐frequency trader chooses to post either market orders or limit orders, which are represented, respectively, by impulse controls and regular controls. We discuss the consequences of the two main features of this microstructure: first, the limit orders are only partially executed, and therefore she has no control on the executed quantity. Second, the high‐frequency trader faces the overtrading risk, which is the risk of large variations in her inventory. The consequences of this risk are investigated in the context of optimal liquidation. The optimal trading problem is studied by stochastic control and dynamic programming methods, and we provide the associated numerical resolution procedure and prove its convergence. We propose dimension reduction techniques in several cases of practical interest. We also detail a high‐frequency trading strategy in the case where a (predictive) directional information on the price is available. Each of the resulting strategies is illustrated by numerical tests.
Petrography and geochemistry of impactites and volcanic bedrock in the ICDP drill core D1c from Lake El'gygytgyn, NE Russia
Authors: Raschke Ulli , Schmitt Ralf T. , Reimold W. Uwe
Published: June 2013

The 3.6 Ma old and 18 km diameter El'gygytgyn impact structure in NE Siberia was drilled in 2008/09 by ICDP (International Continental Scientific Drilling Program). A 517 m long core hole (D1c) was drilled into the outer flank of the central uplift structure, with an overall core recovery of approximately 63%. Thereby, approximately 315 m lake sediments and approximately 202 m impactites were recovered. Here, we present a detailed petrographic and geochemical assessment of the impact breccia and bedrock sections in this core. The 97 m long lower bedrock unit (517–420 m below lake floor [blf]) consists of an ignimbrite. In the overlying upper bedrock unit (420–390 mblf), the core recovered a sequence of similar ignimbrite and several decimeters of mafic rocks. We interpret these units as rocks that are located close to their former, preimpact position, but have been somewhat rotated due to collapse of the central uplift (i.e., it represents parautochthonous basement). From about 390 to 328 mblf occurs a suevite package with an impact melt poor, clast‐dominated matrix, and lithic and mineral clasts that cover the entire range of volcanic target rocks known from the El'gygytgyn region. All stages of shock metamorphism (unshocked to melted) were observed in clasts, and in microclasts of the matrix, of suevite from different depths. Immediately below this package, at the contact to the underlying bedrock, occurs a 1 m wide sheared zone within vitrophyric ignimbrite, which we consider the actual crater floor. The uppermost approximately 12 m, from 328–316 mblf depth, seem to comprise reworked suevite, consisting of a mixture of sediments and suevite with more and, on average, stronger shocked minerals than found in the main suevite unit. This includes a small component of glassy spherules and impact melt fragments. Toward the top of this unit, lake sediments progressively become the dominant material in this section. We assume that this unit contains a fallback component from the ejecta plume that was mixed with the first sediments of the postimpact crater lake, and possibly some rocks that slumped off the inner crater wall—similar to a thin layer at the base of the sediment section of borehole LB‐5A recovered in Lake Bosumtwi (Ghana).
Magmatic history and parental melt composition of olivine‐phyric shergottite LAR 06319: Importance of magmatic degassing and olivine antecrysts in Martian magmatism
Authors: Balta J. Brian , Sanborn Matthew , McSween Harry Y. , Wadhwa Meenakshi
Published: June 2013

Several olivine‐phyric shergottites contain enough olivine that they could conceivably represent the products of closed‐system crystallization of primary melts derived from partial melting of the Martian mantle. Larkman Nunatak (LAR) 06319 has been suggested to represent a close approach to a Martian primary liquid composition based on approximate equilibrium between its olivine and groundmass. To better understand the olivine–melt relationship and the evolution of this meteorite, we report the results of new petrographic and chemical analyses. We find that olivine megacryst cores are generally not in equilibrium with the groundmass, but rather have been homogenized by diffusion to Mg# 72. We have identified two unique grain types: an olivine glomerocryst and an olivine grain preserving a primary magmatic boundary that constrains the time scale of eruption to be on the order of hours. We also report the presence of trace oxide phases and phosphate compositions that suggest that the melt contained approximately 1.1% H2O and lost volatiles during cooling, also associated with an increase in oxygen fugacity upon degassing. We additionally report in situ rare earth element measurements of the various mineral phases in LAR 06319. Based on these reported trace element abundances, we estimate the oxygen fugacity in the LAR 06319 parent melt early in its crystallization sequence (i.e., at the time of crystallization of the low‐Ca and high‐Ca pyroxenes), the rare earth element composition of the parent melt, and those of melts in equilibrium with later formed phases. We suggest that LAR 06319 represents the product of closed‐system crystallization within a shallow magma chamber, with additional olivine accumulated from a cumulate pile. We infer that the olivine megacrysts are antecrysts, derived from a single magma chamber, but not directly related to the host magma, and suggest that mixing of antecrysts within magma chambers may be a common process in Martian magmatic systems.
Marsh thistle in New York: early detection and rapid response to a recent invader
Authors: Hinchey Eamonn , Vogler Donna , Stressler Joseph
Published: June 2013

Case studies implementing early detection and rapid response (EDRR) protocols are crucial to our understanding of how to evaluate the threat of a new invasive organism. Most EDRR schematics depict a linear approach to EDRR beginning with detection, then assessment, and concluding with the rapid response. Our case study exemplified the need to adjust this protocol by interlacing all three phases. Our target species is a recent invader to central New York: Cirsium palustre (marsh thistle). We observed 192 populations and reported them on iMapInvasives.org. These locations were used to generate risk maps of neighboring counties. Six test plots evaluated the plant's bienniality and monocarpism. A life‐stage analysis allowed us to delineate the invasion front to target control and management solutions where they are most effective for marsh thistle. An adaptive approach to EDRR can expedite response strategies, develop risk maps, and train partners for better control.
Locke's Reply to the Skeptic
Authors: Weinberg Shelley
Published: June 2013

Given his representationalism how can Locke claim we have sensitive knowledge of the external world? We can see the skeptic as asking two different questions: how we can know the existence of external things, or more specifically how we can know inferentially of the existence of external things. Locke's account of sensitive knowledge, a form of non‐inferential knowledge, answers the first question. All we can achieve by inference is highly probable judgment. Because Locke's theory of knowledge includes both first order psychological and second order normative conditions, sensitive knowledge can be non‐inferential and less certain than intuitive and demonstrative knowledge.
Targeted molecular trait stacking in cotton through targeted double‐strand break induction
Authors: D'Halluin Kathleen , Vanderstraeten Chantal , Van Hulle Jolien , Rosolowska Joanna , Van Den Brande Ilse , Pennewaert Anouk , D'Hont Kristel , Bossut Martine , Jantz Derek , Ruiter Rene , Broadhvest Jean
Published: June 2013

Recent developments of tools for targeted genome modification have led to new concepts in how multiple traits can be combined. Targeted genome modification is based on the use of nucleases with tailor‐made specificities to introduce a DNA double‐strand break (DSB) at specific target loci. A re‐engineered meganuclease was designed for specific cleavage of an endogenous target sequence adjacent to a transgenic insect control locus in cotton. The combination of targeted DNA cleavage and homologous recombination–mediated repair made precise targeted insertion of additional trait genes (hppd, epsps) feasible in cotton. Targeted insertion events were recovered at a frequency of about 2% of the independently transformed embryogenic callus lines. We further demonstrated that all trait genes were inherited as a single genetic unit, which will simplify future multiple‐trait introgression.
OsDMI3‐mediated activation of OsMPK1 regulates the activities of antioxidant enzymes in abscisic acid signalling in rice
Authors: SHI BEN , NI LAN , LIU YANPEI , ZHANG AYING , TAN MINGPU , JIANG MINGYI
Published: June 2013

It has been shown that the
Ca

2+/calmodulin (CaM)‐dependent protein kinase (CCaMK) OsDMI3 is a novel component of abscisic acid (ABA) signaling in the induction of antioxidant defense in leaves of rice. However, it is not clear how OsDMI3 participates in this process in plants. In this study, we provide evidence to show that there exists a cross‐talk between OsDMI3 and the major ABA‐activated mitogen‐activated protein kinase (MAPK) OsMPK1 in ABA signaling, in which OsDMI3 functions upstream of OsMPK1 to regulate the antioxidant defense systems in rice. These findings provide a novel and interesting insight into the mechanism of CCaMK‐ induced antioxidant defense in ABA signaling.
Predictive modelling of complex agronomic and biological systems
Authors: KEURENTJES JOOST J. B. , MOLENAAR JAAP , ZWAAN BAS J.
Published: June 2013

Biological systems are tremendously complex in their functioning and regulation. Studying the multifaceted behaviour and describing the performance of such complexity has challenged the scientific community for years. The reduction of real‐world intricacy into simple descriptive models has therefore convinced many researchers of the usefulness of introducing mathematics into biological sciences. Predictive modelling takes such an approach another step further in that it takes advantage of existing knowledge to project the performance of a system in alternating scenarios. The ever growing amounts of available data generated by assessing biological systems at increasingly higher detail provide unique opportunities for future modelling and experiment design. Here we aim to provide an overview of the progress made in modelling over time and the currently prevalent approaches for iterative modelling cycles in modern biology. We will further argue for the importance of versatility in modelling approaches, including parameter estimation, model reduction and network reconstruction. Finally, we will discuss the difficulties in overcoming the mathematical interpretation of in vivo complexity and address some of the future challenges lying ahead.
Guideline for treatment of bipolar disorder by the Japanese Society of Mood Disorders, 2012
Authors: Kanba Shigenobu , Kato Tadafumi , Terao Takeshi , Yamada Kazuo ,   Committee for Treatment Guidelines of Mood Disorders, Japanese Society of Mood Disorders, 2012
Published: June 2013

The Japanese Society of Mood Disorders established a committee for treatment guidelines of mood disorders, which created the first edition of a treatment guideline for bipolar disorders on 10 March 2011. The committee has now created a second edition, which we report here. In creating this treatment guideline, the first step was to have several bipolar disorder specialists review well‐conducted studies and meta‐analyses. Based on this evidence, and with a consensus among the specialists, treatment procedures that were considered optimal were compiled and the strength of recommendation for each treatment method was determined. The first draft, prepared in this manner, was further revised through a process of critical investigation by all committee members to produce the final edition.
Helpful Today, But Not Tomorrow? Feeling Grateful as a Predictor of Daily Organizational Citizenship Behaviors
Authors: Spence Jeffrey R. , Brown Douglas J. , Keeping Lisa M. , Lian Huiwen
Published: June 2013

This research extends the existing theoretical understanding of what predicts organizational citizenship behavior (OCB). Using experience sampling techniques, we examine the within‐person relation between OCB and a novel, theoretically relevant predictor: state gratitude. Using 4 independent samples with a total of 210 working adults and 173 undergraduate students, we developed a reliable and valid measure of state gratitude. Drawing upon the moral affect model of gratitude and affective events theory, we conducted 2 experience sampling studies with data collected from 67 (Study 2) and 104 (Study 3) working adults to test the effects of state gratitude on OCB, beyond the effects of several relevant constructs (i.e., state positive affect, dispositional gratitude, and social exchange). Our results advance OCB research and explanations of OCB by modeling OCB as a dynamic, time‐variant construct and by demonstrating that feelings of gratitude, a discrete positive emotion, can be an effective predictor of OCB.
A Case of Successful Pregnancy in a Ewe with Uterus Didelphys
Authors: Carr DJ , Aitken RP , Milne JS , David AL , Wallace JM
Published: June 2013

Contents

Uterus didelphys is a rare congenital abnormality of the reproductive tract. Although it occurs in various species, there are no published reports describing pregnancy outcome in association with this abnormality. Herein we describe a case of successful unilateral singleton pregnancy in a ewe incidentally found to have uterus didelphys during the course of a biomedical research study. The pregnancy was established using assisted reproductive techniques and interrupted in late gestation, at which point the abnormality was identified. Serial ultrasound assessment of foetal biometry revealed a normal foetal growth trajectory. Despite a 45% reduction in placentome number, total placentome weight was near normal secondary to compensatory placentome growth and development. To our knowledge, this is the first detailed report of normal foetal growth in an animal with uterus didelphys and illustrates the ability of the ovine placenta to adapt to a reduced number of placentomes and maintain foetal nutrient supply.
Four Core Social‐Psychological Motivations to Undertake Collective Action
Authors: van Zomeren Martijn
Published: June 2013

Collective action against collective disadvantage is a theoretically and socially relevant phenomenon that has received increased scientific attention in recent years. Because recent work combines different theoretical traditions, the last decade can be rightly called an ‘age of integration’. In this article, I take stock and look ahead by briefly reviewing four core social‐psychological motivations for undertaking collective action (based on identity, morality, emotion, and efficacy). I then review recent accumulating evidence for an encompassing social‐psychological model of collective action that integrates all four core motivations. Based on this model's shortcomings, I close by calling for an ‘age of innovation’ for which I propose a theoretical and research agenda.
Liberale Romandie, radikale Deutschschweiz? Kantonale Demokratien zwischen Repräsentation und Partizipation
Authors: Bühlmann Marc , Vatter Adrian , Dlabac Oliver , Schaub Hans‐Peter
Published: June 2013

Der vorliegende Beitrag untersucht die weit verbreitete These, dass Deutschschweizer Kantone vor allem radikaldemokratische Merkmale aufweisen, während die lateinischen Kantone stärker liberal‐repräsentative Demokratieformen besitzen. Die empirische und mehrdimensionale Messung der Demokratiequalität in den Kantonen zeigt, dass die pauschale These der direktdemokratisch‐partizipatorischen Deutschschweizer Kantone auf der einen Seite und der repräsentativdemokratischen Stände der lateinischen Schweiz auf der anderen Seite der Komplexität der kantonalen Demokratien nicht gerecht wird. Als erklärungskräftige Alternative für die Positionen der Kantone auf den Achsen liberaler und radikaler Demokratien an der Schwelle des 21. Jahrhunderts erweist sich vielmehr die Stärke der liberalen und demokratischen Verfassungsbewegungen in den Kantonen Mitte des 19. Jahrhunderts.
Assessment of immunoglobulin concentrates on thrombogenic activity by thrombin generation assay, prekallikrein activator assay, and size‐exclusion chromatography
Authors: Seifner Alexandra , Beck Gerhard , Bayer Patrick , Eichmeir Stephanie , Lackner Friedrich , Rögelsperger Olga , Weber Katharina , Wollein Gabriele
Published: June 2013

Background

Immunoglobulin G (IgG) concentrates have recently been found to be contaminated with procoagulant impurities causing thromboembolic events (TEEs) in vivo. In this study the question was raised whether a thrombin generation assay (TGA) will be able to characterize IgG samples from the Austrian market with regard to their thrombogenic potential.

Study Design and Methods

A total of 44 IgG concentrates have been assayed by TGA employing pooled normal plasma and Factor (F)XI‐deficient plasma (FXIdp). Furthermore, the prekallikrein activator assay including determination of blank values, size‐exclusion chromatography, and further test systems required for batch release testing of IgG concentrates according to the European Pharmacopeia (Pharm. Eur.) were carried out.

Results

All samples complied with acceptance criteria stated in the Plarm. Eur. and/or prescribed by the marketing approval. One intravenous immunoglobulin (IVIG) involved in TEEs exceeded a threshold level of 350 nmol peak thrombin, which was not exceeded after change of manufacture and by all the other IVIGs tested. Two hyperimmune globulins revealed elevated peak thrombin levels of up to 810 nmol in FXI and up to 285 nmol in FXIdp.

Conclusion

The study indicates that the TGA is able to reliably predict procoagulant activities probably associated with the presence of FXIa and potential thrombogenicity. Comparison of thrombin generation with product‐specific acceptance criteria as well as variables from other test systems as amidolytic activity and molecular size can help to monitor IgG quality and manufacturing changes with regard to thrombogenicity.
A multicenter, randomized, active‐controlled study to investigate the efficacy and safety of intravenous ferric carboxymaltose in patients with iron deficiency anemia
Authors: Onken Jane E. , Bregman David B. , Harrington Robert A. , Morris David , Acs Peter , Akright Bruce , Barish Charles , Bhaskar Birbal S. , Smith‐Nguyen Gioi N. , Butcher Angelia , Koch Todd A. , Goodnough Lawrence T.
Published: June 2013

Background

Many patients receiving oral iron for iron deficiency anemia (IDA) cannot tolerate or fail to respond to therapy, and existing intravenous (IV) iron formulations often require repeated administrations. Ferric carboxymaltose (FCM), a nondextran IV formulation, permits larger single doses.

Study Design and Methods

We evaluated FCM versus oral iron in IDA patients. After 14 days of oral iron, 507 participants responding inadequately to oral iron (hemoglobin [Hb] increase <1 g/dL; Cohort 1) were assigned to Group A (two doses of FCM, 750 mg, 1 week apart) or Group B (oral iron, 325 mg, 3 × day for 14 additional days). Also, 504 subjects not appropriate for oral iron (Cohort 2) were assigned to Group C (FCM as above) or Group D (standard‐of‐care IV iron). The primary efficacy endpoint was change to highest observed Hb from baseline to Day 35. The composite safety endpoint included all‐cause mortality, nonfatal myocardial infarction, nonfatal stroke, unstable angina, heart failure, arrhythmias, and hyper‐ or hypotensive events.

Results

Mean (± standard deviation [SD]) Hb increase was significantly greater in Group A–FCM than Group B–oral iron: 1.57 (±1.19) g/dL versus 0.80 (±0.80) g/dL (p = 0.001). Post hoc comparison of Group C–FCM and Group D–IV standard of care also demonstrated significant mean (±SD) increase in Hb from baseline to highest value by Day 35 in Group C versus Group D: 2.90 (±1.64) g/dL versus 2.16 (±1.25) g/dL (p = 0.001). Safety endpoints occurred in 17 of 499 (3.4%) participants receiving FCM versus 16 of 498 (3.2%) in comparator groups.

Conclusion

Two 750‐mg FCM infusions are safe and superior to oral iron in increasing Hb levels in IDA patients with inadequate oral iron response.
Physical activity is associated with retained muscle metabolism in human myotubes challenged with palmitate
Authors: Green C. J. , Bunprajun T. , Pedersen B. K. , Scheele C.
Published: June 2013

Key points

It is known that saturated fatty acids play a role in the progression of insulin resistance in skeletal muscle while physical activity promotes insulin sensitivity.

The effect of diet and exercise on muscle satellite/stem cells is not well defined: we found that differentiated human muscle satellite cells exhibit metabolic differences. These differences were associated with physical activity level and may reflect a memory of the in vivo environment.

Differentiated muscle satellite cells from physically active individuals have a higher tolerance to saturated fatty acids reflected by a partial protection from fatty acid‐induced insulin resistance.

Physical activity and diet have significant effects on the physiological function of differentiated human muscle satellite cells. As these cells exhibit some phenotypes associated with in vivo adaptations and are involved in muscle maintenance, dysregulatory function could have profound effects on health.

Abstract  The aim of this study was to investigate whether physical activity is associated with preserved muscle metabolism in human myotubes challenged with saturated fatty acids. Human muscle satellite cells were isolated from sedentary or active individuals and differentiated into myocytes in culture. Metabolic differences were then investigated in the basal state or after chronic palmitate treatment. At basal, myocytes from sedentary individuals exhibited higher CD36 and HSP70 protein expression as well as elevated phosphorylation of c‐Jun NH2‐terminal kinase (JNK) and insulin receptor substrate 1 (IRS1) serine307 compared to myocytes from active individuals. Despite equal lipid accumulation following palmitate treatment, myocytes from sedentary individuals exhibited delayed acetyl coenzyme A carboxylase phosphorylation compared to the active group. Myocytes from sedentary individuals had significantly higher basal glucose uptake and palmitate promoted insulin resistance in sedentary myocytes. Importantly, myocytes from active individuals were partially protected from palmitate‐induced insulin resistance. Palmitate treatment enhanced IRS1 serine307 phosphorylation in myocytes from sedentary individuals and correlated positively to JNK phosphorylation. In conclusion, muscle satellite cells retain metabolic differences associated with physical activity. Physical activity partially protects myocytes from fatty acid‐induced insulin resistance and inactivity is associated with dysregulation of metabolism in satellite cells challenged with palmitate. Although the benefits of physical activity on whole body physiology have been well investigated, this paper presents novel findings that both diet and exercise impact satellite cells directly. Given the fact that satellite cells are important for muscle maintenance, a dysregulated function could have profound effects on health. Therefore the effects of lifestyle on satellite cells needs to be delineated.
SNARE proteins are essential in the potentiation of NMDA receptors by group II metabotropic glutamate receptors
Authors: Cheng Jia , Liu Wenhua , Duffney Lara J. , Yan Zhen
Published: June 2013

Key points

Activation of group II metabotropic glutamate receptors (mGluRs) enhances NMDA receptor (NMDAR)‐mediated currents in cortical pyramidal neurons.

In this study, we found that group II mGluR‐induced enhancement of NMDAR currents was associated with increased NMDAR surface expression and synaptic localization.

Inhibition of SNAP‐25 or knockdown of syntaxin 4 blocked the enhancement of NMDAR currents by group II mGluRs.

Group II mGluRs increase the activity of Rab4 small GTPase. Rab4 knockdown or dominant negative Rab4 abolished the enhancing effect of Group II mGluRs on NMDAR currents.

These results suggest that SNARE proteins and Rab4 are key molecules involved in the enhancement of NMDAR exocytosis and function by group II mGluRs. Identification of key molecules involved in NMDAR up‐regulation could provide novel drug targets for schizophrenia treatment.

Abstract  The group II metabotropic glutamate receptors (group II mGluRs) have emerged as the new drug targets for the treatment of mental disorders like schizophrenia. To understand the potential mechanisms underlying the antipsychotic effects of group II mGluRs, we examined their impact on NMDA receptors (NMDARs), since NMDAR hypofunction has been implicated in schizophrenia. The activation of group II mGluRs caused a significant enhancement of NMDAR currents in cortical pyramidal neurons, which was associated with increased NMDAR surface expression and synaptic localization. We further examined whether these effects of group II mGluRs are through the regulation of NMDAR exocytosis via SNARE proteins, a family of proteins involved in vesicle fusion. We found that the enhancing effect of APDC, a selective agonist of group II mGluRs, on NMDAR currents was abolished when botulinum toxin was delivered into the recorded neurons to disrupt the SNARE complex. Inhibiting the function of two key SNARE proteins, SNAP‐25 and syntaxin 4, also eliminated the effect of APDC on NMDAR currents. Moreover, the application of APDC increased the activity of Rab4, a small Rab GTPase mediating fast recycling from early endosomes to the plasma membrane, and enhanced the interaction between syntaxin 4 and Rab4. Knockdown of Rab4 or expression of dominant‐negative Rab4 attenuated the effect of APDC on NMDAR currents. Taken together, these results have identified key molecules involved in the group II mGluR‐induced potentiation of NMDAR exocytosis and function.
Nonlinear Vibration of Gears With Tooth Surface Modifications
Authors: Eritenel Tugan , Parker Robert G.
Published: June 2013

This work provides an analytical solution for the nonlinear vibration of gear pairs that exhibit partial and total contact loss. Partial contact loss is where parts of contact lines lose contact although other parts remain in contact. The gear tooth surface modifications admit an arbitrary combination of profile and lead modifications. Modifications are a source of partial contact loss. The analysis also applies for total contact loss. Unlike models in the literature that are excited by static transmission error or time-varying mesh stiffness, the excitation and the nonlinearity are not a priori specified. Instead, the force-deflection function of the gear pair is provided by an independent source, such as a finite element model or Hertz contact formula. The manipulation of the single-degree-of-freedom oscillator equation of motion yields the excitation and the nonlinearity that arise from Fourier and Taylor series expansions of the force-deflection function. These expansions capture the essential contact behavior that includes tooth profile and lead modifications as well as the bending and shear flexibility of the gear teeth and gear blanks. The method of multiple scales gives the steady-state dynamic response in terms of a frequency-amplitude relation. Comparisons with gear vibration experiments and simulations from the literature that include spur and helical gears with tooth profile and lead modifications verify the method.
Surface Waves on a Half-Space Due to a Time-Harmonic Loading on an Inertial Strip Foundation
Authors: Dehestani M. , Vafai A. , Choobbasti A. J. , Malidarreh N. R. , Szidarovszky F.
Published: June 2013

An analytical approach has been applied to obtain the solution of Navier's equation for a homogeneous, isotropic half-space under an inertial foundation subjected to a time-harmonic loading. Displacement potentials were used to change the Navier's equation to a system of wave-type equations. Calculus of variation was employed to demonstrate the contribution of the foundation's inertial effects as boundary conditions. Use of the Fourier transformation method for the system of Poisson-type equations and applying the boundary conditions yielded the transformed surface displacement field. Direct contour integration has been employed to achieve the surface waves. In order to clarify the foundation's inertial effects, related coefficients were defined and a parametric study was conducted. Final results revealed that increasing the mass per unit length of the foundation or the frequency of the applied harmonic load intensifies the inertial effect factors. On the other hand, an increase in strip width or Poisson's ratio would imply reduction in the inertial effect factors.
Aeroelastic Stability and Response of Composite Swept Wings in Subsonic Flow Using Indicial Aerodynamics
Authors: Sina S. A. , Farsadi T. , Haddadpour H.
Published: June 2013

In this study, the aeroelastic stability and response of an aircraft swept composite wing in subsonic compressible flow are investigated. The composite wing was modeled as an anisotropic thin-walled composite beam with the circumferentially asymmetric stiffness structural configuration to establish proper coupling between bending and torsion. Also, the structural model consists of a number of nonclassical effects, such as transverse shear, material anisotropy, warping inhibition, nonuniform torsional model, and rotary inertia. The finite state form of the unsteady aerodynamic loads have been modeled based on the indicial aerodynamic theory and strip theory in the subsonic compressible flow. Novel Mach dependent exponential approximations of the indicial aerodynamic functions have been developed. The extended Galerkin’s method was used to construct the mass, stiffness, and damping matrices of the nonconservative aeroelastic system. Eigen analysis of the system was performed to obtain the aeroelastic instability (divergence and flutter) boundaries. Also, solving the equations of motion in the time domain leads to the aeroelastic response of wing in different flight speeds. The obtained results are compared with the available results in the literature, which reveals an excellent agreement. The numerical results obtained in this article seek to clarify the effects of geometrical and material couplings and flight Mach number on the aeroelastic instability and response of composite wings in subsonic compressible flow.
Development of a Self-Opening Neural Interface
Authors: Cutrone Annarita , Bossi Sivia , Micera Silvestro
Published: June 2013

This article illustrates the development and preliminary results of SELINE, a self-opening neural interface. The advantages of this innovative neural interface are: higher selectivity due to its three-dimensional structure and efficient anchorage system to the nervous tissue. The device is made of polyimide that is a lightweight, flexible and biocompatible polymer. The electrode has been microfabricated using lithographic techniques; electrical and mechanical tests have been performed to evaluate the integrity of the device. Successful results have been obtained in the development of the electrode with excellent mechanical and electrical properties.
Monte Carlo modeling for dose assessment in cone beam CT for oral and maxillofacial applications
Authors: Zhang G. , Marshall N. , Bogaerts R. , Jacobs R. , Bosmans H.
Published: June 2013

Purpose:

To adjust Monte Carlo modeling for dose assessment in dedicated cone beam computed tomography (CBCT) of the oral and maxillofacial region.

Methods:

Two different CBCT systems with different fields of view (FOVs), beam qualities, and scan geometries were modeled using Monte Carlo simulation. Dose calculations for typical CBCT examinations were performed with the head and neck part of four computational anatomical phantoms.

Results:

Simulation results compared favorably to values acquired experimentally using physical phantoms (in the literature). For a given phantom scanned with 90 kV and 60 × 60 mm FOV, effective dose per mAs was on average the same for the two different systems. Exposing the four phantoms under identical settings for the same CBCT system resulted in variations in organ doses of greater than 100%, leading to differences in effective dose of 30%. For one system, the dose dependence on the operating tube potential can be described with a quadratic polynomial function. Dose distributions over the axial plane were presented as contour plots.

Conclusions:

Monte Carlo modeling is an efficient and accurate means of evaluating dose distributions for dedicated cone beam oral and maxillofacial CT. Results suggest large dose differences among patients undergoing the same examination on a given system, supporting approaches toward patient specific dosimetry. A dedicated and standardized computational phantom for head and neck dosimetry should be established.
A moving blocker system for cone‐beam computed tomography scatter correction
Authors: Ouyang Luo , Song Kwang , Wang Jing
Published: June 2013

Purpose:

Scatter contamination in cone‐beam computed tomography (CBCT) degrades the image quality by introducing shading artifacts. A moving‐blocker‐based approach has been proposed to simultaneously estimate scatter and reconstruct the complete volume within field of view (FOV) from a single CBCT scan. Promising results were obtained from our simulation studies. In this work, the authors demonstrated experimentally the effectiveness of the moving‐blocker‐based scatter correction approach by implementing a moving blocker system on a LINAC on‐board kV CBCT imaging system.

Methods:

A physical attenuator (i.e., “blocker”) consisting of equal spaced lead strips was mounted on a linear actuator. A step motor connected to the actuator drove the blocker to move back and forth along gantry rotation axis during the CBCT acquisition. Scatter signal was estimated from the blocked region of imaging panel, and interpolated into the unblocked region. A statistics‐based iterative image reconstruction algorithm was used to reconstruct CBCT images from unblocked projections after the scatter signal was subtracted. Experimental studies were performed on a Catphan phantom and an anthropomorphic pelvis phantom to evaluate performance of the moving blocker system.

Results:

The scatter‐induced shading artifacts were substantially reduced in the images acquired with the moving blocker system. CT number error in selected regions of interest reduced from 318 to 17 and from 239 to 10 for the Catphan phantom and pelvis phantom, respectively.

Conclusions:

The authors demonstrated experimentally that the moving blocker system can successfully estimate the scatter signal in projection data and obtain complete volumetric information within the FOV using a single scan.
Does the γ dose distribution comparison technique default to the distance to agreement test in clinical dose distributions?
Authors: Low Daniel A. , Morele Delphine , Chow Philip , Dou Tai H. , Ju Tao
Published: June 2013

Purpose:

To determine the validity of the assumption that the γ dose distribution comparison tool defaults to the distance to agreement test under conditions of clinically relevant steep dose gradients and γ test criteria.

Methods:

The assumption was tested by computing the angle θ between the dose axis and γ vector for clinical treatment plans. θ was a function of the evaluated dose distribution dose gradient and the ratio (α) of the dose difference to distance to agreement (DTA) criteria. Dose distributions from prostate, head and neck, and lung clinical treatment plans were examined: 50 treatment plans were selected for each of the prostate and head neck sites and 27 treatment plans were selected for lung. Dose‐gradient histograms were prepared for each of the treatment plans using α = 1%/mm (e.g., 3%, 3 mm dose difference and DTA criteria, respectively). To determine how frequently different values of α were used in publications, papers that referenced the original γ paper were examined to identify the dose difference and DTA criteria used in those publications. In order to compare θ calculated using α = 1%/mm to θ for other values of α, the relationship between θ and α was determined.

Results:

For most of the targets and critical structures, the maximum value of θ approached 90°, so the assumption that the γ tool defaulted to the DTA test in steep dose gradients was correct. Most of the published papers using the γ tool employed the 3%, 3 mm dose difference and DTA criteria, respectively. Most of the other evaluations used criteria such that α ⩾ 1%/mm, so the conclusions relating to the examined dose distributions applied. There were a few papers employing very small values of α (including one where α = 0.17%/mm), breaking the assumption that the γ dose comparison tool defaulted to the DTA tool in steep dose gradients.

Conclusions:

Most published cases utilized values of α ⩾ 1%/mm, and for those the implicit assumption that the γ dose comparison tool defaults to the DTA test in steep dose gradient regions was true. There were a few cases for which α was small enough to potentially invalidate this assumption. Care should be taken by investigators when selecting the γ test criteria to assure that the γ test will appropriately default to the DTA test in the steepest dose gradients being evaluated.
On deriving the Maxwellian velocity distribution
Authors: Walstad Allan
Published: June 2013

Maxwell's 1860 derivation of the molecular velocity distribution does not constitute a valid approach for pedagogical use.
Tensors: A guide for undergraduate students
Authors: Battaglia Franco , George Thomas F.
Published: June 2013

A guide on tensors is proposed for undergraduate students in physics or engineering that ties directly to vector calculus in orthonormal coordinate systems. We show that once orthonormality is relaxed, a dual basis, together with the contravariant and covariant components, naturally emerges. Manipulating these components requires some skill that can be acquired more easily and quickly once a new notation is adopted. This notation distinguishes multi-component quantities in different coordinate systems by a differentiating sign on the index labelling the component rather than on the label of the quantity itself. This tiny stratagem, together with simple rules openly stated at the beginning of this guide, allows an almost automatic, easy-to-pursue procedure for what is otherwise a cumbersome algebra. By the end of the paper, the reader will be skillful enough to tackle many applications involving tensors of any rank in any coordinate system, without index-manipulation obstacles standing in the way.
Rotating frame analysis of rigid body dynamics in space phasor variables
Authors: Bhattacharjee Shayak
Published: June 2013

We propose a new method of attacking problems in rigid body rotation, focusing on the heavy symmetric top. The technique is a direct extension of the method traditionally applied to the free symmetric top. We write Euler's equations in a frame which is attached to the top and thus shares its entire angular velocity. The structure of the resulting equations is such that it is advantageous to cast and solve them in terms of complex variables (space phasors). Through this formalism, we obtain a direct link between the initial conditions at the time of launch and the subsequent behavior of the top. The insertion of a damping term allows us to further explain the behavior of a top where the pivot is non-ideal and has friction. Finally, we make some suggestions regarding experimental verification of our results.