bluuebunny/crossref_metadata_2025 huggingface dataset:
Seismic wave propagation in anisotropic ice – Part 1: Elasticity tensor and derived quantities from ice-core properties
Authors: Diez A. , Eisen O.
Published: August 2014

Abstract. A preferred orientation of the anisotropic ice crystals influences the viscosity of the ice bulk and the dynamic behaviour of glaciers and ice sheets. Knowledge about the distribution of crystal anisotropy, to understand its contribution to ice dynamics, is mainly provided by crystal orientation fabric (COF) data from ice cores. However, the developed anisotropic fabric does not only influence the flow behaviour of ice, but also the propagation of seismic waves. Two effects are important: (i) sudden changes in COF lead to englacial reflections and (ii) the anisotropic fabric induces an angle dependency on the seismic velocities and, thus, also recorded traveltimes. A framework is presented here to connect COF data with the elasticity tensor to determine seismic velocities and reflection coefficients for cone and girdle fabrics from ice-core data. We connect the microscopic anisotropy of the crystals with the macroscopic anisotropy of the ice mass, observable with seismic methods. Elasticity tensors for different fabrics are calculated and used to investigate the influence of the anisotropic ice fabric on seismic velocities and reflection coefficients, englacially as well as for the ice-bed contact. Our work, therefore, provides a contribution to remotely determine the state of bulk ice anisotropy.
Seismic wave propagation in anisotropic ice – Part 2: Effects of crystal anisotropy in geophysical data
Authors: Diez A. , Eisen O. , Hofstede C. , Lambrecht A. , Mayer C. , Miller H. , Steinhage D. , Binder T. , Weikusat I.
Published: August 2014

Abstract. We investigate the propagation of seismic waves in anisotropic ice. Two effects are important: (i) sudden changes in crystal orientation fabric (COF) lead to englacial reflections; (ii) the anisotropic fabric induces an angle dependency on the seismic velocities and, thus, recorded traveltimes. Velocities calculated from the polycrystal elasticity tensor derived for the anisotropic fabric from measured COF eigenvalues of the EDML ice core, Antarctica, show good agreement with the velocity trend determined from a vertical seismic profiling. The agreement of the absolute velocity values, however, depends on the choice of the monocrystal elasticity tensor used for the calculation of the polycrystal properties. With this validation of seismic velocities we make use of abrupt changes in COF as common reflection mechanism for seismic and radar data below the firn–ice transition to investigate their occurrence by comparison with ice-core data. Our results highlight the possibility to complement regional radar surveys with local, surface-based seismic deployment to separate isochrones in radar data from other mechanisms. This is important for the reconnaissance of future ice-core drill sites, where accurate isochrone (i.e. non-COF) layer integrity allows for synchronization with other cores, as well as studies of ice dynamics considering non-homogeneous viscosity from preferred crystal orientations.
A Possible Correction of the Face Inversion Effect: A Methodological Commentary
Authors: Rakover SAM S. , CAHLON Baruch
Published: August 2014

The face inversion effect is based on 2 phenomena: Recognition of faces presented upright (hair above, chin below) is better than that of faces presented inverted (chin above, hair below), and inversion impairs recognition of faces more than of nonfacial objects (buildings, cars). Based on theoretical and empirical considerations, this article suggests that in many cases the size of the second phenomenon is overestimated, because it is influenced by recognition of upright faces being higher than recognition of upright objects (i.e., a baseline-level effect). A mathematically based correction is suggested for the baseline-level effect. It rests on the assumption that recognition of inverted faces depends on recognition of upright faces. Theoretical and empirical support is offered for this assumption. Also, an empirical base for the proposed correction is provided.
Effects of Gender, Imagery Ability, and Sports Practice on the Performance of a Mental Rotation Task
Authors: HABACHA HAMDI , MOLINARO CORINNE , DOSSEVILLE FABRICE
Published: August 2014

Mental rotation is one of the main spatial abilities necessary in the spatial transformation of mental images and the manipulation of spatial parameters. Researchers have shown that mental rotation abilities differ between populations depending on several variables. This study uses a mental rotation task to investigate effects of several factors on the spatial abilities of 277 volunteers. The results demonstrate that high and low imagers performed equally well on this tasks. Athletes outperformed nonathletes regardless of their discipline, and athletes with greater expertise outperformed those with less experience. The results replicate the previously reported finding that men exhibit better spatial abilities than women. However, with high amounts of practice, the women in the current study were able to perform as well as men.
Monetary and Affective Judgments of Consumer Goods: Modes of Evaluation Matter
Authors: SETA JOHN J. , SETA CATHERINE E. , MCCORMICK MICHAEL , GALLAGHER ASHLEIGH H.
Published: August 2014

Participants who evaluated 2 positively valued items separately reported more positive attraction (using affective and monetary measures) than those who evaluated the same two items as a unit. In Experiments 1–3, this separate/unitary evaluation effect was obtained when participants evaluated products that they were purchasing for a friend. Similar findings were obtained in Experiments 4 and 5 when we considered the amount participants were willing to spend to purchase insurance for items that they currently owned. The averaging/summation model was contrasted with several theoretical perspectives and implicated averaging and summation integration processes in how items are evaluated. The procedural and theoretical similarities and differences between this work and related research on unpacking, comparison processes, public goods, and price bundling are discussed. Overall, the results support the operation of integration processes and contribute to an understanding of how these processes influence the evaluation and valuation of private goods.
CONDITIONS FOR EXACT CAVALIERI ESTIMATION
Authors: Tinajero-Bravo Mónica , Eslava-Gómez Guillermina , Cruz-Orive Luis Manuel
Published: August 2014

Exact Cavalieri estimation amounts to zero variance estimation of an integral with systematic observations along a sampling axis. A sufficient condition is given, both in the continuous and the discrete cases, for exact Cavalieri sampling. The conclusions suggest improvements on the current stereological application of fractionator-type sampling.
Metabolic balance of coastal Antarctic waters revealed by autonomous pCO2 and ΔO2/Ar measurements
Authors: Tortell Philippe D. , Asher Elizabeth C. , Ducklow Hugh W. , Goldman Johanna A. L. , Dacey John W. H. , Grzymski Joseph J. , Young Jodi N. , Kranz Sven A. , Bernard Kim S. , Morel François M. M.
Published: August 2014

We use autonomous gas measurements to examine the metabolic balance (photosynthesis minus respiration) of coastal Antarctic waters during the spring/summer growth season. Our observations capture the development of a massive phytoplankton bloom and reveal striking variability in pCO2 and biological oxygen saturation (ΔO2/Ar) resulting from large shifts in community metabolism on time scales ranging from hours to weeks. Diel oscillations in surface gases are used to derive a high‐resolution time series of net community production (NCP) that is consistent with 14C‐based primary productivity estimates and with the observed seasonal evolution of phytoplankton biomass. A combination of physical mixing, grazing, and light availability appears to drive variability in coastal Antarctic NCP, leading to strong shifts between net autotrophy and heterotrophy on various time scales. Our approach provides insight into the metabolic responses of polar ocean ecosystems to environmental forcing and could be employed to autonomously detect climate‐dependent changes in marine primary productivity.
The extension of ionospheric holes into the tail of Venus
Authors: Collinson G. A. , Fedorov A. , Futaana Y. , Masunaga K. , Hartle R. , Stenberg G. , Grebowsky J. , Holmström M. , Andre N. , Barabash S. , Zhang T. L.
Published: August 2014

Ionospheric holes are Cytherian nightside phenomena discovered by the NASA Pioneer Venus Orbiter, featuring localized plasma depletions driven by prominent and unexplained enhancements in the draped interplanetary magnetic field. Observed only during solar maximum, the phenomenon remains unexplained, despite their frequent observation during the first 3 years of the mission and more than 30 years having elapsed since their first description in the literature. We present new observations by the European Space Agency Venus Express showing that ionospheric holes can extend much further into the tail than previously anticipated (1.2 to 2.4 planetary radii) and may be observed throughout the solar cycle and over a wide range of solar wind conditions. We find that ionospheric holes are a manifestation of a deeper underlying phenomenon: tubes of enhanced draped interplanetary magnetic field that emerge in pairs from below the ionosphere and stretch far down the tail. We speculate on two possible explanations for the magnetic fields underlying the phenomena: magnetic pileup due to stagnation of ionospheric flow and internal draping around a metallic core.
PC index as a proxy of the solar wind energy that entered into the magnetosphere: Development of magnetic substorms
Authors: Troshichev O. A. , Podorozhkina N. A. , Sormakov D. A. , Janzhura A. S.
Published: August 2014

The Polar Cap (PC) index has been approved by the International Association of Geomagnetism and Aeronomy (IAGA XXII Assembly, Merida, Меxico, 2013) as a new index of magnetic activity. The PC index can be considered to be a proxy of the solar wind energy that enters the magnetosphere. This distinguishes PC from AL and Dst indices that are more related to the dissipation of energy through auroral currents or storage of energy in the ring current during magnetic substorms or storms. The association of the PC index with the direct coupling of the solar wind energy into the magnetosphere is based upon analysis of the relationship of PC with parameters in the solar wind, on the one hand, and correlation between the time series of PC and the AL index (substorm development), on the other hand. This paper (the first of a series) provides the results of statistical investigations that demonstrate a strong correlation between the behavior of PC and the development of magnetic substorms. Substorms are classified as isolated and expanded. We found that (1) substorms are preceded by growth in the РС index, (2) sudden substorm expansion onsets are related to “leap” or “reverse” signatures in the PC index which are indicative of a sharp increase in the PC growth rate, (3) substorms start to develop when PC exceeds a threshold level 1.5 ± 0.5 mV/m irrespective of the length of the substorm growth phase, and (4) there is a linear relation between the intensity of substorms and PC for all substorm events.
Equatorial ionization anomaly variability over the Brazilian region during boreal sudden stratospheric warming events
Authors: Paes R. R. , Batista I. S. , Candido C. M. N. , Jonah O. F. , Santos P. C. P.
Published: August 2014

This study refers to the connection between the stratosphere and ionosphere, investigating, specifically, the behavior of the equatorial ionization anomaly (EIA) and ionospheric effects over the Brazilian region during sudden stratospheric warming (SSW) events. We studied three major warmings that occurred in the Northern Hemisphere winter 2007–2008, 2008–2009, and 2009–2010 and a minor warming that occurred in 2010–2011. The solar activity was low for the first two cases and relatively moderate for the last two. In this study the EIA behavior was investigated using the ΔTEC (total electron content) parameter, which expresses the EIA relative intensity for the Brazilian sector. The results for the Brazilian region show, mainly after SSW temperature peak, an increase in the EIA intensity in the morning, followed by a decrease in the afternoon. As identified through ΔTEC signatures and consistently confirmed through wavelet power spectra analysis, this semidiurnal behavior is preserved for a number of days equal to the polar region thermal stabilization phase and it is very similar to the results obtained in pioneer studies in the Peruvian sector, in which TEC data was also used. In some cases the TEC negative variation is stronger than the positive, being noticeably more intense around the prereversal enhancement time, when the EIA is strongly suppressed in the Brazilian sector.
Source scaling relations and along‐strike segmentation of slow slip events in a 3‐D subduction fault model
Authors: Liu Yajing
Published: August 2014

Scaling between slip event duration and equivalent moment is diagnostic of the underlying physics of rupture process. For episodic slow slip events (SSEs) in subduction zones, their moment‐duration relation is not clearly defined and shows considerable variation among individual margins where multiple episodes of SSEs are geodetically detected. Here I set up a 3‐D planar thrust fault model within the framework of rate‐state friction to study the spatiotemporal evolution of slip and stress during SSEs. SSE source properties, including along‐strike length, duration, equivalent moment, and stress drop, are quantified, and their scaling relations are compared to observations. Modeled SSEs have nearly constant stress drops of 0.001 to 0.01 MPa, due to near‐lithostatic pore pressure at the SSE depths. The modeled moment‐duration scaling is between 1 (linear) and 2 (squared). When multiple SSEs appear simultaneously along the strike, the stress interaction between approaching slip fronts results in higher average propagation speeds for longer lengths, which leads to a scaling close to 2. When SSEs are well offset in space and time, stress interaction is negligible and the scaling is close to 1. Two types of SSE along‐strike segmentation gaps are identified from model results. The “primary” gaps are persistent segmentation boundaries due to along‐strike variation of effective normal stress, while the “secondary” gaps evolve through SSE cycles and reflect the stress condition within a primary segment. This implies that some geodetically inferred SSE segmentation boundaries may result from slower slip velocities below the resolution limits of geodetic inversion models.
Computational analysis of nonlinear creep of polyphase aggregates: Influence of phase morphology
Authors: Cook A. C. , Vel S. S. , Gerbi C. , Johnson S. E.
Published: August 2014

The constitutive laws of polyphase aggregates dominantly depend on the operative deformation mechanisms, phase morphology and modes, and environmental conditions. Each of these factors has the potential to dramatically affect bulk mechanical properties as well as the local stress and strain rate distributions. To focus on the effects of phase morphology, we have developed a rigorous multiscale approach based on asymptotic expansion homogenization. The proposed methodology has two fundamental goals: (1) accurately predict bulk behavior in aggregates by explicitly taking into account phase morphology and (2) calculate detailed distributions of strain rates, stresses, and viscosities in heterogeneous materials. The methodology is able to consider general nonlinear phase constitutive laws that relate strain rates to stresses, temperature, and other factors such as water fugacity and grain size. We demonstrate the approach by analyzing power law creep of computer‐generated and natural polyphase systems and benchmarking the results against analytical solutions. As an outcome of this analysis, we find that the approximation of an aggregate as a power law material is reasonable for isotropic, homogeneous phase distributions but breaks down significantly with high degrees of phase organization. We also present distributions in strain rate, stress, and viscosity for different applied loading conditions. Results exhibit areas of high internal stresses and substantial localization. We describe and provide a freely available software package supporting these calculations.
Linear repetitive learning controls for nonlinear systems by Padé approximants
Authors: Tomei P. , Verrelli C. M.
Published: August 2014

We discuss the use of [m,m]‐Padé approximants in the implementation of repetitive learning controls solving the output tracking problem (via output error feedback) in the presence of uncertain periodic reference and/or disturbance signals with known common period. The aim is to address the stability issues concerning those approximants when a linear learning controller—designed through a detailed stability proof (involving the use of a suitable Lyapunov‐like function) and described by a transfer function exhibiting all its poles with negative real part—is to be obtained as well as to evaluate the corresponding closed‐loop performances: robustness (for instance with respect to additive disturbance noises due to unmodeled sensor dynamics) is consequently achieved with improvements in the output tracking errors appearing as the approximation order m increases. Even though the case of any relative degree may be explicitly addressed, in this paper, for the sake of clarity, we restrict our attention to the learning problem for the class of single‐input, single‐output, minimum phase, time‐invariant systems with known relative degree ρ = 2, uncertain parameters and uncertain output‐dependent nonlinearities. Numerical simulation results illustrate the theoretical derivations. Copyright © 2014 John Wiley & Sons, Ltd.
Liquid Marbles for High‐Throughput Biological Screening of Anchorage‐Dependent Cells
Authors: Oliveira Nuno M. , Correia Clara R. , Reis Rui L. , Mano João F.
Published: August 2014

Stable liquid marbles (LM) are produced by coating liquid droplets with a hydrophobic powder. The used hydrophobic powder is produced by fluorosi­lanization of diatomaceous earth, used before to produce superhydrophobic structures. Here, the use of LM is proposed for high‐throughput drug screening on anchorage‐dependent cells. To provide the required cell adhesion sites inside the liquid environment of LM, surface‐modified poly(l‐lactic acid) microparticles are used. A simple method that takes advantage from LM appealing features is presented, such as the ability to inject liquid on LM without disrupting (self‐healing ability), and to monitor color changes inside of LM. After promoting cell adhesion, a cytotoxic screening test is performed as a proof of concept. Fe3+ is used as a model cytotoxic agent and is injected on LM. After incubation, AlamarBlue reagent is injected and used to assess the presence of viable cells, by monitoring color change from blue to red. Color intensity is measured by image processing and the analysis of pictures takes using an ordinary digital camera. The proposed method is fully validated in counterpoint to an MTS (3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carbo​xymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐te​trazolium) colorimetric assay, a well‐known method used for the cytotoxicity assessment.
Highly Efficient and Stable Phosphorescent Organic Light‐Emitting Diodes Utilizing Reverse Intersystem Crossing of the Host Material
Authors: Fukagawa Hirohiko , Shimizu Takahisa , Kamada Taisuke , Kiribayashi Yukihiro , Osada Yoshichika , Hasegawa Munehiro , Morii Katsuyuki , Yamamoto Toshihiro
Published: August 2014

Phosphorescent organic‐light emitting diodes (PHOLEDs) exhibit an internal quantum efficiency of 100% and their early practical realization is expected. One of the main challenges in PHOLEDs is to improve the operational stability of green and blue devices. Triplet exciton dynamics in stable PHOLEDs, which are different from those in unstable PHOLEDs, are shown. An efficient and stable green PHOLED is demonstrated by employing a suitable host that surrounds the phosphorescent dopant. The transient photoluminescence characteristics show that the triplet excitons of the host, which are generally unstable, are rapidly transferred to the dopant and emit phosphorescence in the stable PHOLED. Most of the triplet excitons of the host in the stable PHOLED are transferred to the dopant within 10 ns, following the Förster process by utilizing reverse intersystem crossing from the triplet state to the singlet state. The findings also provide a design strategy for hosts to enable realization of highly stable full‐color PHOLEDs.
The Role of Photon Energy in Free Charge Generation in Bulk Heterojunction Solar Cells
Authors: Di Nuzzo Daniele , Koster L. Jan Anton , Gevaerts Veronique S. , Meskers Stefan C. J. , Janssen René A. J.
Published: August 2014

To determine the role of photon energy on charge generation in bulk heterojunction solar cells, the bias voltage dependence of photocurrent for excitation with photon energies below and above the optical band gap is investigated in two structurally related polymer solar cells. Charges generated in (poly[2,6‐(4,4‐bis(2‐ethylhexyl)‐4H‐cyclopenta[2,1‐b;3,4‐b′′]dithiophene)‐alt‐4,7‐(2,1,3‐benzothia­diazole)] (C‐PCPDTBT):[6,6]‐phenyl‐C61‐butyric acid methyl ester (PCBM) solar cells via excitation of the low‐energy charge transfer (CT) state, situated below the optical band gap, need more voltage to be extracted than charges generated with excitation above the optical band gap. This indicates a lower effective binding energy of the photogenerated electrons and holes when the excitation is above the optical band gap than when excitation is to the bottom of the CT state. In blends of PCBM with the silicon‐analogue, poly[(4,4‐bis(2‐ethylhexyl)dithieno[3,2‐b:2′,3′‐d]silole)‐2,6‐diyl‐alt‐(2,1,3‐benzothiadiazole)‐4,7‐diyl] (Si‐PCPDTBT), there is no effect of the photon energy on the electric field dependence of the dissociation efficiency of the CT state. C‐PCPDTBT and Si‐PCPDTBT have very similar electronic properties, but their blends with PCBM differ in the nanoscale phase separation. The morphology is coarser and more crystalline in Si‐PCPDTBT:PCBM blends. The results demonstrate that the nanomorphological properties of the bulk heterojunction are important for determining the effective binding energy in the generation of free charges at the heterojunction.
A multicenter, open‐label phase II study of recombinant CPT (Circularly Permuted TRAIL) plus thalidomide in patients with relapsed and refractory multiple myeloma
Authors: Geng Chuanying , Hou Jian , Zhao Yaozhong , Ke Xiaoyan , Wang Zhao , Qiu Lugui , Xi Hao , Wang Fuxu , Wei Na , Liu Yan , Yang Shifang , Wei Peng , Zheng Xiangjun , Huang Zhongxia , Zhu Bing , Chen Wen‐Ming
Published: August 2014

Circularly permuted TRAIL (CPT), a recombinant mutant of human Apo2L/TRAIL, is a novel antitumor candidate for multiple myeloma (MM) and other hematologic malignancies. In this phase II study, the safety and efficacy of CPT plus thalidomide was investigated in thalidomide‐resistant MM patients. A total of 43 patients were recruited into three CPT plus thalidomide cohorts based on CPT dosage in sequence: 5 mg/kg (n = 11), 8 mg/kg (n = 17), and 10 mg/kg (n = 15). CPT was administered via intravenous infusion on days 1–5, and thalidomide was given orally at 100 mg once daily in each 21‐day cycle. The overall response rate (ORR) of 41 efficacy‐evaluable patients was 22.0% (2 complete response, 3 near complete response, and 4 partial response). No significant difference in the ORR was observed among the three dose cohorts; however, the ORR tended to be higher with the higher‐dose regimen. Median progression‐free survival and median duration of response were 6.6 months and 6.1 months, respectively. The most common treatment‐related adverse events (TRAEs) were neutropenia (46.5%), leukopenia (41.9%), fever (37.2%), elevated AST (32.6%), and elevated ALT (20.9%). TRAEs of Grade 3–4 were mainly neutropenia (18.6%), anemia (9.3%), elevated AST (7.0%), and leukopenia (4.7%). No significant differences were found in the incidence and severity of TRAEs among the three cohorts. In conclusion, CPT plus thalidomide was well tolerated with no occurrence of dose‐limiting toxicities and demonstrated promising antitumor activity in RRMM patients. CPT at 10 mg/kg for 5 days in combination with thalidomide and dexamethason will be studied in the next clinical trial. Am. J. Hematol. 89:1037–1042, 2014. © 2014 Wiley Periodicals, Inc.
A comparison of methods for assessing mortality risk
Authors: Levine Morgan E. , Crimmins Eileen M.
Published: August 2014

Objectives

Concepts such as Allostatic Load, Framingham Risk Score, and Biological Age were developed to combine information from multiple measures into a single latent variable that can be used to quantify a person's biological state. Given these varying approaches, the goal of this article is to compare how well these three measures predict subsequent all‐cause and disease‐specific mortality within a large nationally representative U.S. sample.

Methods

Our study population consisted of 9,942 adults, ages 30 and above from National Health and Nutrition Examination Survey III. Receiver Operating Characteristic curves and Cox Proportional Hazard models for the whole sample and for stratified age groups were used to compare how well Allostatic Load, Framingham Risk Score, and Biological Age predict ten‐year all‐cause and disease‐specific mortality in the sample, for whom there were 1,076 deaths over 96,420 person years of exposure.

Results

Overall, Biological Age predicted 10‐year mortality more accurately than other measures for the full age range, as well as for participants ages 50 to 69 and 70+. Additionally, out of the three measures, Biological Age had the strongest association with all‐cause and cancer mortality, while the Framingham Risk Score had the strongest association with CVD mortality.

Conclusions

Methods for quantifying biological risk provide important approaches to improving our understanding of the causes and consequences of changes in physiological function and dysregulation. Biological Age offers an alternative and, in some cases a more accurate summary approach to the traditionally used methods, such as Allostatic Load and Framingham Risk Score. Am. J. Hum. Biol. 26:768–776, 2014. © 2014 Wiley Periodicals, Inc.
Area‐level socioeconomic disparities impact adult overweight and obesity risks of han ethnicity in China
Authors: Zhao Dapeng , Zheng Lianbin , Li Yonglan , Yu Keli , Zhang Xinghua
Published: August 2014

Objectives

The profound socioeconomic processes occurring in developing countries have been accompanied by the notable increase of overweight and obese populations. This study for the first time investigates the impact of area‐based socioeconomic status (SES) on adult overweight and obesity for both sexes of Han ethnicity in China.

Methods

We investigated 6,221 adult participants of Han ethnicity from 18 geographic areas in China, and measured stature and weight for each participant. The mean annual income per individual was chosen as the area‐level SES index. We adopted logistic regression analysis to explore the relationship of area‐level SES with overweight and obesity.

Results

The age‐adjusted overweight and obesity prevalence was 32.46% for men and 29.27% for women respectively. Substantial area‐level SES disparity in overweight and obesity risks for both sexes exist in China. The overweight and obesity prevalence rates increased with increasing SES levels in men rather than in women.

Conclusion

Men living in high SES areas as well as women living at the lowest SES areas were most likely to be at the highest risk of overweight and obesity in China. Am. J. Hum. Biol. 27:129–132, 2015. © 2014 Wiley Periodicals, Inc.
Diffuse angiopathy in Adams‐Oliver syndrome associated with truncating DOCK6 mutations
Authors: Lehman Anna , Stittrich Anna‐Barbara , Glusman Gustavo , Zong Zheyuan , Li Hong , Eydoux Patrice , Senger Christof , Lyons Christopher , Roach Jared C. , Patel Millan
Published: August 2014

Adams‐Oliver syndrome (AOS) is a rare malformation syndrome characterized by the presence of two anomalies: aplasia cutis congenita of the scalp and transverse terminal limb defects. Many affected individuals also have additional malformations, including a variety of intracranial anomalies such as periventricular calcification in keeping with cerebrovascular microbleeds, impaired neuronal migration, epilepsy, and microcephaly. Cardiac malformations can be present, as can vascular dysfunction in the forms of cutis marmorata telangiectasia congenita, pulmonary vein stenoses, and abnormal hepatic microvasculature. Elucidated genetic causes include four genes in different pathways, leading to a model of AOS as a multi‐pathway disorder. We identified an infant with mild aplasia cutis congenita and terminal transverse limb defects, developmental delay and a severe, diffuse angiopathy with incomplete microvascularization. Whole‐genome sequencing documented two rare truncating variants in DOCK6, a gene associated with a type of autosomal recessive AOS that recurrently features periventricular calcification and impaired neurodevelopment. We highlight an unexpectedly high frequency of likely deleterious mutations in this gene in the general population, relative to the rarity of the disease, and discuss possible explanations for this discrepancy. © 2014 Wiley Periodicals, Inc.
Genetic testing and corresponding services among individuals with autism spectrum disorder (ASD)
Authors: Cuccaro Michael L. , Czape Kayla , Alessandri Michael , Lee Joycelyn , Deppen Abigail Rupchock , Bendik Elise , Dueker Nicole , Nations Laura , Pericak‐Vance Margaret , Hahn Susan
Published: August 2014

The purpose of this study was to assess use of genetic testing and corresponding genetic services for children with Autism Spectrum Disorder (ASD). Survey data from 397 parents of individuals with ASD was collected using the Center for Autism and Related Disabilities client registry. Participants reported that 41.2% of the individuals with ASD had undergone any type of genetic testing. However, only 21.3% of individuals with ASD had been referred to a genetics specialist. Diagnosis and level of functioning were significantly associated with both referral to a genetics specialist and having undergone any genetic testing. In addition, Hispanic ancestry was associated with increased referral to genetic testing. Concerns about the limited benefits of genetic testing and prohibitive costs were potential barriers to pursuing genetic testing. Overall, low numbers of individuals with ASD have a history of undergoing genetic testing or receiving genetic services. Possible reasons include low referral rates as well as concerns by parents about cost and relevance, and lack of availability. These findings confirm the historical trend for providing genetic testing and genetic services to those with the greatest impairments. © 2014 Wiley Periodicals, Inc.
The formation of inflammatory demyelinated lesions in cerebral white matter
Authors: Maggi Pietro , Macri Sheila M. Cummings , Gaitán María I. , Leibovitch Emily , Wholer Jillian E. , Knight Heather L. , Ellis Mary , Wu Tianxia , Silva Afonso C. , Massacesi Luca , Jacobson Steven , Westmoreland Susan , Reich Daniel S.
Published: August 2014

Objective

Vascular permeability and inflammatory demyelination are intimately linked in the brain, but what is their temporal relationship? We aimed to determine the radiological correlates of the earliest tissue changes accompanying demyelination in a primate model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE) in the common marmoset.

Methods

By 7T magnetic resonance imaging (MRI), T1 maps, proton density, and T2‐weighted images were acquired before and after EAE induction in 5 marmosets (every other week before lesions appeared, weekly thereafter). From scans before and after intravenous injection of contrast material, we measured the evolution of lesional blood–brain barrier (BBB) permeability, comparing in vivo MRI to postmortem tissue examination.

Results

On average, BBB permeability increased 3.5‐fold (p < 0.0001) over the 4 weeks prior to lesion appearance. Permeability gradually decreased after lesion appearance, with attendant changes in the distribution of inflammatory cells (predominantly macrophages and microglia) and demyelination. On tissue analysis, we also identified small perivascular foci of microglia and T cells without blood‐derived macrophages or demyelination. These foci had no visible MRI correlates, although permeability within the foci, but not outside, increased in the weeks before the animals died (p < 0.0001).

Interpretation

This study provides compelling evidence that in marmoset EAE, which forms lesions strongly resembling those of MS, early changes in vascular permeability are associated with perivascular inflammatory cuffing and parenchymal microglial activation but precede the arrival of blood‐derived monocytes that accompany demyelination. Prospective detection of transient permeability changes could afford an opportunity for early intervention to forestall tissue damage in newly forming lesions. Ann Neurol 2014;76:594–608
Many‐body and spin‐orbit effects on direct‐indirect band gap transition of strained monolayer MoS2 and WS2
Authors: Wang Luqing , Kutana Alex , Yakobson Boris I.
Published: August 2014

Monolayer transition metal dichalcogenides are promising materials for photoelectronic devices. Among them, molybdenum disulphide (MoS2) and tungsten disulphide (WS2) are some of the best candidates due to their favorable band gap values and band edge alignments. Here, various perturbative corrections to the DFT electronic structure, e.g. GW, spin‐orbit coupling, as well as many‐body excitonic and trionic effects are considered, and accurate band gaps as a function of homogeneous biaxial strain in these materials are calculated. All of these corrections are shown to be of comparable magnitudes and need to be included in order to obtain an accurate electronic structure. The strain at which the direct‐to‐indirect gap transition occurs is calculated. After considering all contributions, the direct to indirect gap transition strain is predicted to be at 2.7% in MoS2 and 3.9% in WS2. These values are generally higher than the previously reported theoretical values.
Detektion lokaler und zeitlicher Veränderungen der Elektrodengrenzschicht in Lithium‐Ionen‐Batterien mit dem elektrochemischen Rastermikroskop
Authors: Bülter Heinz , Peters Fabian , Schwenzel Julian , Wittstock Gunther
Published: July 2014

Die Grenzschicht zwischen Elektrode und Elektrolyt (SEI; solid electrolyte interphase) in Lithium‐Ionen‐Batterien trennt das stark reduzierende lithiierte Graphit von reduzierbaren Elektrolytbestandteilen. Sie ist von kritischer Bedeutung für die Leistungsfähigkeit, Haltbarkeit und den sicheren Betrieb der Batterien. In‐situ‐Abbildung der SEI wird mit dem Feedback‐Modus der elektrochemischen Rastermikroskopie mit 2,5‐Di‐tert‐butyl‐1,4‐dimethoxybenzol als Mediator demonstriert. Die Bildung der SEI wird über eine Verringerung der Regenerationskinetik des Mediators beobachtet. Kontinuierliche Abbildungen einzelner Probenregionen zeigen Fluktuationen der passivierenden Eigenschaften auf einer Zeitskala von 2 min bis zu 20 h mit einer inhomogenen Verteilung über den Bildausschnitt. Die Implikationen des demonstrierten Herangehens für die In‐situ‐Bewertung lokaler SEI‐Eigenschaften auf Graphitelektroden werden in Bezug auf die Untersuchungen des Einflusses mechanischer Spannungen auf die Zuverlässigkeit der SEI und des Wirkungsprinzips von Elektrolytadditiven zur Verbesserung der SEI‐Eigenschaften diskutiert.
Three‐Dimensional Constrained Tracking Control Via Exact Differentiation Estimator of a Quadrotor Helicopter
Authors: Ghommam Jawhar , Charland Guillaume , Saad Maarouf
Published: August 2014

In this paper, a constructive method is presented to design a three dimensional trajectory tracking controller that forces a quadrotor helicopter to track a bounded and sufficiently smooth reference trajectory asymptotically in the presence of constant force disturbances. The quadrotor helicopter under consideration has fewer independent thrusters than degrees of freedom to be controlled. Motivated by the vehicle's steering practices, the roll and pitch angles are regarded as virtual controls along with four control forces to fulfill the task of position and yaw angle reference tracking. To prevent position constraint violation, the barrier Lyapunov function (BLF) is employed in the vectorial backstepping procedure to guarantee that the position and attitude constraints are not violated. The backstepping procedure employs an exact and robust sliding mode differentiator of order two to facilitate the implementation of the attitude command signal without calculating the virtual control signal derivative analytically.
A Bayesian SIRS model for the analysis of respiratory syncytial virus in the region of Valencia, Spain
Authors: Corberán‐Vallet Ana , Santonja Francisco J.
Published: August 2014

We present a Bayesian stochastic susceptible‐infected‐recovered‐susceptible (SIRS) model in discrete time to understand respiratory syncytial virus dynamics in the region of Valencia, Spain. A SIRS model based on ordinary differential equations has also been proposed to describe RSV dynamics in the region of Valencia. However, this continuous‐time deterministic model is not suitable when the initial number of infected individuals is small. Stochastic epidemic models based on a probability of disease transmission provide a more natural description of the spread of infectious diseases. In addition, by allowing the transmission rate to vary stochastically over time, the proposed model provides an improved description of RSV dynamics. The Bayesian analysis of the model allows us to calculate both the posterior distribution of the model parameters and the posterior predictive distribution, which facilitates the computation of point forecasts and prediction intervals for future observations.
Assays for determination of ertapenem for applications in therapeutic drug monitoring, pharmacokinetics and sample stability
Authors: Pickering Matthew K. , Brown Stacy D.
Published: August 2014

Carbapanems are a class of β‐lactam antibiotics with broad‐spectrum potency and high β‐lactamase resistance. Ertapenem, a member of this class, sold under the trade name Invanz™, has been of interest in the world of antibiotic therapeutic drug monitoring owing to its highly standardized 1 g dose and its high degree of plasma protein binding. Owing to the relative newness of this drug, fewer than 30 methods for ertapenem quantification have been published. Among these about half utilize biological matrices at the sample type. Liquid‐liquid extraction and protein precipitation prevail as the most frequently used sample preparation techniques, despite their low recoveries compared with solid‐phase extraction. Additionally, high‐performance liquid chromatography with ultraviolet detection (HPLC‐UV) is the instrumentation choice for most ertapenem assays. While these approaches may not achieve the highest possible sensitivity for ertapenem quantification, they provide clinically relevant tools for monitoring ertapenem in real patients. Sample stability is an ongoing concern for laboratories that handle ertapenem analysis, with buffering being of paramount importance, as well as low temperature (<−70°C) storage, to ensure minimal drug degradation in situ. Copyright © 2014 John Wiley & Sons, Ltd.
Pancreas divisum: A common developmental variant that deserves attention in preclinical medical education
Authors: White Jessica J. , Roberts Zoey N. , Gest Thomas R. , Beale Elmus G.
Published: August 2014

Clinical literature indicates that pancreas divisum (PD) is present in 3–22% of the population and may be associated with an increased risk of pancreatitis. PD is a developmental variant wherein the duct systems derived from the dorsal and ventral pancreatic buds are not fused. Hence secretions from the head, neck, body, and tail, which develop from the dorsal bud, must pass through the minor duodenal papilla. The smaller uncinate process, derived from the ventral bud, drains through the major duodenal papilla. The purpose of this study was: (1) to do a cadaveric dissection to confirm whether PD is common in donors who had not been selected because they had pancreatitis and (2) to determine the frequency of PD descriptions in anatomy, embryology, pathology, and surgery books in our libraries. For our anatomical study, pancreata of eight human donors were dissected. Dye was injected into the ducts so that any communications between main and accessory ducts could be easily located. For our literature review, 22 anatomy, 14 embryology, 11 pathology, and 26 surgery books were examined for mention of PD. PD was unambiguously identified in two donor cadavers. However, only 14% of the anatomy plus embryology books compared to 70% of the surgery plus pathology books describe PD. Cadaveric dissection confirms that PD is indeed prevalent. The prevalence of PD with its increased risk of pancreatitis merits inclusion of this topic in textbooks of anatomy and embryology. Clin. Anat. 27:1038–1045, 2014. © 2014 Wiley Periodicals, Inc.
Patterns of innervation of the lacrimal gland with clinical application
Authors: Scott Gabriel , Balsiger Heather , Kluckman Matthew , Fan Jerry , Gest Thomas
Published: August 2014

Parasympathetic stimulation of the lacrimal gland is responsible for tear production, and this innervation originates from fibers conveyed in the facial nerve. After synapse in the pterygopalatine ganglion, postsynaptic parasympathetic fibers travel within the zygomatic and zygomaticotemporal nerves (ZTN) into the orbit. As described in most anatomy texts, ZTN communicates with the lacrimal nerve (LN) posterior to the gland and then secretomotor fibers enter the gland. This study was performed to gain a better understanding of the innervation of the lacrimal gland. Seventeen cadaver heads were bisected for a total of 34 sides, which then underwent dissection of the superolateral orbital region to observe the course for the LN and ZTN. Three variations of the course of the LN and ZTN were found. In 20 (60.6%) dissections it was documented that the ZTN entered directly into the lacrimal gland with no communication with the LN. In 12 (36.4%) of the bisected heads, ZTN had both a direct connection into the gland and a communicating branch with the LN. In only one (3.0%) bisected head, ZTN communicated with the LN before entering the gland as it is commonly described in anatomy texts. Our study reveals that the ZTN usually takes a different course than is classically described in most anatomy textbooks. A greater understanding of the typical course these nerves take may help surgeons identify them more easily and avoid damaging them. Clin. Anat. 27:1174–1177, 2014. © 2014 Wiley Periodicals, Inc.
Cytotoxic and DNA‐targeted therapy in urothelial cancer: Have we squeezed the lemon enough?
Authors: Balar Arjun V. , Milowsky Matthew I.
Published: August 2014

Urothelial cancer has long been known as a chemotherapy‐sensitive disease. However, clinical trial data to date suggest a plateau to the magnitude of benefit from cytotoxic therapy alone. In spite of level 1 evidence supporting cisplatin‐based chemotherapy for patients with muscle‐invasive and metastatic urothelial cancer, underuse prevails among patients with localized disease and only a modest survival benefit exists in the metastatic setting, although trials have consistently demonstrated that there is a subset of patients who clearly benefit. Recent comprehensive genomic profiling has identified a high prevalence of actionable genomic alterations as well as other potential targets yet to be fully understood. Modern clinical trials must now focus on identifying predictive biomarkers to select those patients who will benefit most from cytotoxic chemotherapy, molecularly targeted therapy, or potentially both. Cancer 2015;121:179–87. © 2014 American Cancer Society.
Patient preferences in advanced or recurrent ovarian cancer
Authors: Havrilesky Laura J. , Alvarez Secord Angeles , Ehrisman Jessie A. , Berchuck Andrew , Valea Fidel A. , Lee Paula S. , Gaillard Stephanie L. , Samsa Greg P. , Cella David , Weinfurt Kevin P. , Abernethy Amy P. , Reed Shelby D.
Published: August 2014

BACKGROUND

The objective of this study was to elucidate relative preferences of women with ovarian cancer for symptoms, treatment‐related side effects, and progression‐free survival (PFS) relevant to choosing a treatment regimen.

METHODS

Women with advanced or recurrent ovarian cancer participated in a survey that included 3 methods to measure patient preferences (ratings, rankings, and a discrete‐choice experiment) for 7 attributes: mode of administration, visit frequency, peripheral neuropathy, nausea and vomiting, fatigue, abdominal discomfort, and PFS. Participants were asked to choose between 2 unlabeled treatment scenarios that were characterized using the 7 attributes. Each participant completed 12 choice questions in which attribute levels were assigned according to an experimental design and a fixed‐choice question representing 2 chemotherapy regimens for ovarian cancer.

RESULTS

In total, 95 women completed the survey. Participants' ratings and rankings revealed greater concern and importance for PFS than for any other attribute (P < .0001 for all). The discrete‐choice experiment revealed that the relative odds that a participant would choose a scenario with 18 months, 21 months, and 24 months of PFS versus 15 months of PFS were 1.5 (P = .01), 3.4 (P < .001), and 7.5 (P < .001), respectively. However, participants' choices indicated that they were willing to accept a shorter PFS to avoid severe side effects: 6.7 months to reduce nausea and vomiting from severe to mild, 5.0 months to reduce neuropathy from severe to mild, and 3.7 months to reduce abdominal symptoms from severe to moderate.

CONCLUSIONS

PFS is the predominant driver of patient preferences for chemotherapy regimens. However, women in the current study were willing to trade significant PFS time for reductions in treatment‐related toxicity. Cancer 2014;120:3651–3659. © 2014 American Cancer Society.