bluuebunny/crossref_metadata_2025 huggingface dataset:
On the impact of masking and blocking hypotheses for measuring the efficacy of new tuberculosis vaccines
Authors: Arregui Sergio , Sanz Joaquín , Marinova Dessislava , Martín Carlos , Moreno Yamir
Published: February 2016

Over the past 60 years, theMycobacterium bovisbacille Calmette–Guérin (BCG) has been used worldwide to prevent tuberculosis (TB). However, BCG has shown a very variable efficacy in different trials, offering a wide range of protection in adults against pulmonary TB. One of the most accepted hypotheses to explain these inconsistencies points to the existence of a pre-existing immune response to antigens that are common to environmental sources of mycobacterial antigens andMycobacterium tuberculosis. Specifically, two different mechanisms have been hypothesized to explain this phenomenon: the masking and the blocking effects. According to masking hypothesis, previous sensitization confers some level of protection against TB that masks vaccine’s effects. In turn, the blocking hypothesis postulates that previous immune response prevents vaccine taking of a new TB vaccine. In this work we introduce a series of models to discriminate between masking and blocking mechanisms and address their relative likelihood. We apply our methodology to the data reported by BCG-REVAC clinical trials, which were specifically designed for studying BCG efficacy variability. Our results yield estimates that are consistent with high levels of blocking (41% in Manaus -95% CI [14–68]- and 96% in Salvador -95% CI [52–100]-). Moreover, we also show that masking does not play any relevant role in modifying vaccine’s efficacy either alone or in addition to blocking. The quantification of these effects around a plausible model constitutes a relevant step towards impact evaluation of novel anti-tuberculosis vaccines, which are susceptible of being affected by similar effects, especially if applied on individuals previously exposed to mycobacterial antigens.
Testing the effects of perimeter fencing and elephant exclosures on lion predation patterns in a Kenyan wildlife conservancy
Authors: Dupuis-Desormeaux Marc , Davidson Zeke , Pratt Laura , Mwololo Mary , MacDonald Suzanne E.
Published: February 2016

The use of fences to segregate wildlife can change predator and prey behaviour. Predators can learn to incorporate fencing into their hunting strategies and prey can learn to avoid foraging near fences. A twelve-strand electric predator-proof fence surrounds our study site. There are also porous one-strand electric fences used to create exclosures where elephant (and giraffe) cannot enter in order to protect blocs of browse vegetation for two critically endangered species, the black rhinoceros (Diceros bicornis) and the Grevy’s zebra (Equus grevyi). The denser vegetation in these exclosures attracts both browsing prey and ambush predators. In this study we examined if lion predation patterns differed near the perimeter fencing and inside the elephant exclosures by mapping the location of kills. We used a spatial analysis to compare the predation patterns near the perimeter fencing and inside the exclosures to predation in the rest of the conservancy. Predation was not over-represented near the perimeter fence but the pattern of predation near the fence suggests that fences may be a contributing factor to predation success. Overall, we found that predation was over-represented inside and within 50 m of the exclosures. However, by examining individual exclosures in greater detail using a hot spot analysis, we found that only a few exclosures contained lion predation hot spots. Although some exclosures provide good hunting grounds for lions, we concluded that exclosures did not necessarily create prey-traps per se and that managers could continue to use this type of exclusionary fencing to protect stands of dense vegetation.
Amyloid properties of the leader peptide of variant B cystatin C: implications for Alzheimer and macular degeneration
Authors: Sant'Anna Ricardo , Navarro Susanna , Ventura Salvador , Paraoan Luminita , Foguel Debora
Published: February 2016

Variant B (VB) of cystatin C has a mutation in its signal peptide (A25T), which interferes with its processing leading to reduced secretion and partial retention in the vicinity of the mitochondria. There are genetic evidences of the association of VB with Alzheimer's disease (AD) and age‐related macular degeneration (AMD). Here, we investigated aggregation and amyloid propensities of unprocessed VB combining computational and in vitro studies. Aggregation predictors revealed the presence of four aggregation‐prone regions, with a strong one at the level of the signal peptide, which indeed formed toxic aggregates and mature amyloid fibrils in solution. In light of these results, we propose for the first time the role of the signal peptide in pathogenesis of AD and AMD.
Is the subarctic landscape still a carbon sink? Evidence from a detailed catchment balance
Authors: Lundin Erik J. , Klaminder Jonatan , Giesler Reiner , Persson Andreas , Olefeldt David , Heliasz Michal , Christensen Torben R. , Karlsson Jan
Published: February 2016

Climate warming raises the question whether high‐latitude landscape still function as net carbon (C) sinks. By compiling an integrated C balance for an intensely studied subarctic catchment, we show that this catchment's C balance is not likely to be a strong current sink of C, a commonly held assumption. In fact, it is more plausible (71% probability) that the studied catchment functions as a C source (−11 ± 20 g C m−2 yr−1). Analyses of individual fluxes indicate that soil and aquatic C losses offset C sequestering in other landscape components (e.g., peatlands and aboveground forest biomass). Our results stress the importance of fully integrated catchment C balance estimates and highlight the importance of upland soils and their interaction with the aquatic network for the catchment C balance.
F2 region response to geomagnetic disturbances across Indian latitudes: O(1S) dayglow emission
Authors: Upadhayaya A. K. , Gupta Sumedha , Brahmanandam P. S.
Published: February 2016

The morphology of ionospheric storms has been investigated across equatorial and low latitudes of Indian region. The deviation in F2 region characteristic parameters (foF2 and h′F) along with modeled green line dayglow emission intensities is examined at equatorial station Thiruvananthapuram (8.5°N, 76.8°E, 0.63°S geomagnetic latitude) and low‐latitude station Delhi (28.6°N, 77.2°E,19.2°N geomagnetic latitude) during five geomagnetic storm events. Both positive and negative phases have been noticed in this study. The positive storm phase over equatorial station is found to be more frequent, while the drop in ionization in most of the cases was observed at low‐latitude station. It is concluded that the reaction as seen at different ionospheric stations may be quite different during the same storm depending on both the geographic and geomagnetic coordinates of the station, storm intensity, and the storm onset time. Modulation in the F2 layer critical frequency at low and equatorial stations during geomagnetic disturbance of 20–23 November 2003 was caused by the storm‐induced changes in O/N2. It is also found that International Reference Ionosphere 2012 model predicts the F2 layer characteristic (foF2 and h′F) parameters at both the low and equatorial stations during disturbed days quite reasonably. A simulative approach in GLOW model developed by Solomon is further used to estimate the changes in the volume emission rate of green line dayglow emission under quiet and strong geomagnetic conditions. It is found that the O(1S) dayglow thermospheric emission peak responds to varying geomagnetic conditions.
Neogene magnetostratigraphy and rock magnetic study of the Kashi Depression, NW China: Implications to neotectonics in the SW Tianshan Mountains
Authors: Qiao Qingqing , Huang Baochun , Piper John D. A. , Deng Tao , Liu Chengying
Published: February 2016

The southwest Tianshan Mountains of China are bordered by the Tarim foreland and comprise an actively deforming segment of the India‐Asia collisional system. We report a detailed magnetostratigraphic study of the Dashankou section in the Kashi Depression of the Tarim Basin to improve the understanding of the history of sedimentation, denudation, and mountain building in this region. The preferred correlation of the succession with the geomagnetic polarity timescale defines a depositional history between 12.4 and 3.0 Ma with a substantial increase in sedimentation rates identified at ~6.7 Ma corresponding to a pulse of rapid uplift in the southwest Tianshan Mountains. Although climatic changes may have modulated the record during Neogene times, they do not appear to have had an important influence on sediment accumulation rates between 7.0 and 2.6 Ma. Magnetic fabrics identify the influence of a regional stress field imparted by ongoing India‐Asia collision in the lower part of the succession contrasting with predominantly sedimentary fabrics in the higher part of the succession. A major clastic influx with a maximum age estimate of ~3.6 Ma comprises the Xiyu conglomerates, and integration with other magnetostratigraphic investigations around the Tianshan demonstrates unambiguously that depositional onset of this coarse clastic episode is diachronous. Hence, the Xiyu Formation cannot be considered as a chronostratigraphic marker related to any specific tectonic or climatic event.
Evaluation of long‐term surface‐retrieved cloud droplet number concentration with in situ aircraft observations
Authors: Lim Kyo‐Sun Sunny , Riihimaki Laura , Comstock Jennifer M. , Schmid Beat , Sivaraman Chitra , Shi Yan , McFarquhar Greg M.
Published: February 2016

A new operational retrieval of cloud droplet number concentration (ND) at cloud base has been produced from surface remote sensors at the Atmospheric Radiation Measurement (ARM) Southern Great Plains site for 13 years from January 1998 to January 2011. The retrieval is based on surface radiometer measurements of cloud optical depth from the multifilter rotating shadow band radiometer and liquid water path from the microwave radiometer (MWR). It is only applicable for single‐layered overcast warm (stratus or stratocumulus) clouds. Evaluation with in situ aircraft measurements during the extended‐term aircraft field campaign, Routine ARM Aerial Facility (AAF) Clouds with Low Optical Water Depths (CLOWD) Optical Radiative Observations (RACORO), shows that the retrieved ND robustly reproduces the primary mode of the in situ measured probability density function (PDF) but produces too wide a distribution, primarily caused by frequent high cloud droplet number concentration. Our analysis shows that the error in the MWR retrievals at low liquid water paths is one possible reason for this deficiency. Modification through the diagnosed liquid water path from the coordinate solution improves not only the PDF of the retrieved ND but also the relationship between the cloud droplet number concentration and cloud droplet effective radius. Consideration of entrainment effects rather than assuming an adiabatic cloud improves the values of the ND retrieval by reducing the magnitude of cloud droplet number concentration. Aircraft measurements and retrieval comparisons suggest that retrieving the vertical distribution of cloud droplet number concentration and effective radius is feasible with an improvement of the parameter representing the mixing effects between environment and clouds and with a better understanding of the effect of mixing degree on cloud properties.
The geologic history of Margaritifer basin, Mars
Authors: Salvatore M. R. , Kraft M. D. , Edwards C. S. , Christensen P. R.
Published: February 2016

In this study, we investigate the fluvial, sedimentary, and volcanic history of Margaritifer basin and the Uzboi‐Ladon‐Morava outflow channel system. This network of valleys and basins spans more than 8000 km in length, linking the fluvially dissected southern highlands and Argyre basin with the northern lowlands via Ares Vallis. Compositionally, thermophysically, and morphologically distinct geologic units are identified and are used to place critical relative stratigraphic constraints on the timing of geologic processes in Margaritifer basin. Our analyses show that fluvial activity was separated in time by significant episodes of geologic activity, including the widespread volcanic resurfacing of Margaritifer basin and the formation of chaos terrain. The most recent fluvial activity within Margaritifer basin appears to terminate at a region of chaos terrain, suggesting possible communication between surface and subsurface water reservoirs. We conclude with a discussion of the implications of these observations on our current knowledge of Martian hydrologic evolution in this important region.
Eocene‐Oligocene proto‐Cascades topography revealed by clumped (Δ47) and oxygen isotope (δ18O) geochemistry (Chumstick Basin, WA, USA)
Authors: Methner Katharina , Fiebig Jens , Wacker Ulrike , Umhoefer Paul , Chamberlain C. Page , Mulch Andreas
Published: February 2016

The topography of the present‐day Washington Cascades impacts atmospheric circulation and precipitation patterns in the Pacific Northwest, introducing a pronounced orographic rain shadow in the lee of the mountain range. The temporal development of Cascade topography, however, remains largely unconstrained for the early Cenozoic. Based on coupled carbonate clumped isotope (Δ47) and oxygen isotope (δ18O) measurements we reconstruct δ18O values of Eocene groundwater (δ18Owater) in the Chumstick basin (central Washington), today located in the Cascade rain shadow. Δ47 (paleo)thermometry indicates a systematic change in basin burial temperatures from 110°C to 70°C depending on burial depth in the basin. These data are in good agreement with low‐T thermochronological and vitrinite reflectance data, and further constrain the basin burial and exhumation history. In concert with field observations, microstructural analysis, and δ18O values of the analyzed carbonates, we suggest that the Δ47 temperatures and δ18O values reflect open‐system carbonate cement recrystallization in meteoric‐derived groundwaters during early burial diagenesis. Assuming open‐system behavior, reconstructed mean δ18Owater values of ~ −7‰ (middle Eocene) to −9‰ (late Eocene/early Oligocene) are consistent with a low‐elevation origin of the corresponding meteoric waters that permeated the sandstone/conglomerate members of the Eocene sedimentary units. In light of the paleogeographic setting of the Chumstick basin, the reconstructed δ18Owater values agree well with Pacific‐derived moisture that did not experience strong rainout. The absence of a rain shadow effect therefore permits only moderate Eocene/Oligocene elevations at least for the southern part of the Washington proto‐Cascades.
The Southern Annular Mode determines interannual and centennial‐scale fire activity in temperate southwest Tasmania, Australia
Authors: Mariani Michela , Fletcher Michael‐Shawn
Published: February 2016

Southern Annular Mode (SAM) is the primary mode of atmospheric variability in the Southern Hemisphere. While it is well established that the current anthropogenic‐driven trend in SAM is responsible for decreased rainfall in southern Australia, its role in driving fire regimes in this region has not been explored. We examined the connection between fire activity and SAM in southwest Tasmania, which lies in the latitudinal band of strongest correlation between SAM and rainfall in the Southern Hemisphere. We reveal that fire activity during a fire season is significantly correlated with the phase of SAM in the preceding year using superposed epoch analysis. We then synthesized new 14 charcoal records from southwest Tasmania spanning the last 1000 years, revealing a tight coupling between fire activity and SAM at centennial timescales, observing a multicentury increase in fire activity over the last 500 years and a spike in fire activity in the 21st century in response to natural and anthropogenic SAM trends.
Typical and Atypical Human Functional Brain Development
Authors: de Haan Michelle , Johnson Mark H.
Published: February 2016

Developmental cognitive neuroscience focuses on studying the normal development of brain–behavior relationships, as well as how factors such as neurodevelopmental disorder, brain injury, or atypical environments affect these relationships. This chapter first overviews three theoretical frameworks for investigating and interpreting developing brain‐behavior relationships. The predictions of the interactive specialization framework are then explored in more detail by reviewing brain imaging studies of normal development and brain imaging studies of atypical development including developmental disorders such as autism and attention deficit hyperactivity disorder, brain injury resulting in impaired face processing, memory and language, and atypical experiences such as perceptual impairment and child maltreatment. The results support the interactive specialization view of increased specialization and localization of brain response and changes in the dynamics of brain networks with age. The chapter concludes by highlighting untested predictions of the interactive specialization framework and discussing advances in methodology important for future work in the field.
Characteristics of cryptogenic stroke in cancer patients
Authors: Gon Yasufumi , Okazaki Shuhei , Terasaki Yasukazu , Sasaki Tsutomu , Yoshimine Toshiki , Sakaguchi Manabu , Mochizuki Hideki
Published: February 2016

Objective

To clarify the characteristics of cryptogenic stroke in patients with active cancer.

Methods

Patients with or without cancer diagnosed with acute ischemic stroke between January 2006 and February 2015 were extracted from a prospectively collected stroke database of Osaka University Hospital. Patients were categorized according to the presence of active cancer and known stroke mechanisms.

Results

Among 1191 patients with acute ischemic stroke, 145 (12%) had active cancer. Patients with active cancer were diagnosed more often with cryptogenic stroke than were patients without cancer (47% vs. 12%, P < 0.001). Compared with cryptogenic stroke patients without cancer, cryptogenic stroke patients with active cancer had fewer atherosclerotic risk factors, lower nutrition status, higher plasma D‐dimer levels, and multiple vascular lesions. In a multivariate logistic analysis, plasma D‐dimer level (odds ratio [OR] per 1 standard deviation increase: 6.30; 95% confidence interval [CI]: 2.94–15.69; P < 0.001), and the presence of multiple vascular lesions (OR: 6.40; 95% CI: 2.35–18.35; P < 0.001) were independent predictors of active cancer. When comparing active cancer patients who had known stroke mechanisms with those who had cryptogenic stroke, high plasma D‐dimer levels, multiple vascular lesions, and receiving chemotherapy and/or radiation therapy were associated with cryptogenic stroke etiology.

Interpretation

In cryptogenic stroke, patients with active cancer has a unique pathology characterized by high plasma D‐dimer levels and multiple vascular lesions. The hypercoagulable state and malnutrition due to cancer and its treatments potentially influence the development of cryptogenic stroke in cancer patients.
Crosslinked Continuous Glass Fiber‐Reinforced Toughened Polypropylene Composites
Authors: Gohs Uwe , Girdauskaite Lina , Peitzsch Lutz , Rothe Stefan , Zschech Carsten , Heinrich Gert , Rödel Hartmut
Published: February 2016

The authors prepared crosslinkable toughened polypropylene to be used for simultaneous spinning of hybrid yarn and the preparation of continuous glass fiber‐reinforced polypropylene composites by filament winding to be consolidated by compression molding. A subsequent electron treatment aims on crosslinking of matrix as well as enhancement of interfacial adhesion in the interphase of glass fiber‐reinforced polypropylene composites. The authors evaluate the crosslinking behavior as well as the tensile properties of crosslinkable toughened polypropylene. Finally, the authors use transverse tensile test and single fiber pull‐out test in order to study the effect of matrix modification and electron treatment on continuous glass fiber‐reinforced polypropylene composites as well as on single glass fiber polypropylene model microcomposites.
Ultra‐Fast One‐Step Fabrication of Cu2Se Thermoelectric Legs With Ni–Al Electrodes by Plasma‐Activated Reactive Sintering Technique
Authors: Wu Linchun , Su Xianli , Yan Yonggao , Uher Ctirad , Tang Xinfeng
Published: February 2016

In this study, a novel ultra‐fast method is developed to fabricate thermoelectric (TE) legs and electrodes from raw elemental materials in just one‐step plasma‐activated reactive sintering (PARS) process. We have demonstrated this approach with TE legs made of Cu2Se and the Ni–Al multiphase composite electrode. The obtained Cu2Se material shows a maximum ZT value of 0.9 at 773 K. The lowest specific interfacial resistivity of the as‐prepared Cu2Se/electrode junction is about 30 mΩ cm2 at room temperature. The interfacial bonding strength is about 10 MPa. This method shows great prospects for large‐scale, low‐cost, and rapid fabrication of thermoelectric modules.
Enhancement of the Power Conversion Efficiency in Organic Photovoltaics by Unveiling the Appropriate Polymer Backbone Enlargement Approach
Authors: Chochos Christos L. , Singh Ranbir , Kim Min , Gasparini Nicola , Katsouras Athanasios , Kulshreshtha Chandramouli , Gregoriou Vasilis G. , Keivanidis Panagiotis E. , Ameri Tayebeh , Brabec Christoph J. , Cho Kilwon , Avgeropoulos Apostolos
Published: February 2016

Optoelectronic properties, supramolecular assemblies, and morphology variation of polymeric semiconductors are governed by six fundamental chemical features. These features are molecular weight, bond length alternation (BLA), planarity, aromatic resonance energy, substituents, and intermolecular interactions. Of these features the specific role of BLA in determining the performance of a polymeric semiconductor in practical technological applications is so far unknown. This study investigates this question and reports the novel finding that the optoelectronic, microscopic (supramolecular packing), and macroscopic (morphology variation and device performance) properties of model semiconducting polymers depend on the conjugated polymer backbone enlargement, which is directly related to the BLA. Extensive studies are performed in both single‐component polymer films and their blends with fullerene derivatives. Understanding the specific structure‐properties relations will lead to significant advancement in the area of organic electronics, since it will set new design rules toward further optimization of polymer chemical structures to enhance the device performances.
Enhancing the Thermal Characteristics of Shape‐Stabilized Phase Change Nanocomposite Nanofibers by Incorporation of Multiwalled Carbon Nanotubes within the Nanofibrous Structure
Authors: Esmaeilzadeh Zahra , Rezaei Babak , Mousavi Shoushtari Ahmad , Mojtahedi Mohammad Reza Mohaddes
Published: February 2016

In this study, the authors employed a good dispersion of multiwalled carbon nanotubes (MWCNTs) within the phase change material (PCM)/polymer (polyethylene glycol/polyacrylonitrile) electrospinning solution to enhance the thermal properties of shape‐stabilized phase change nanocomposite nanofibers (SPCNNs). In this regard, nanofibers with and without MWCNTs were produced (with approximately similar diameters), and the effect of a good dispersion of MWCNTs on the thermal, physical, and mechanical properties of the nanofibrous samples was evaluated. Scanning electron microscopy and transmission electron microscopy were utilized to observe the surface morphology and interior structures of electrospun nanofibers, respectively. Differential scanning calorimeter (DSC) and thermogravimetric analysis were utilized to evaluate the degree of crystallinity (DOC) and thermal stability of the samples, respectively. The DSC results of phase change nanofibers (PCNs) and the phase change nanocomposite nanofibers (PCNNs) confirmed that the presence of MWCNTs extremely boosts the DOC of nanofibers (44.69% and 93.64% for PCNs and PCNNs, respectively), which can be attributed to the nucleation effect of MWCNTs. Moreover, the X‐ray diffraction pattern and tensile test results showed that the presence of MWCNTs can affect the average size of crystals and mechanical strength of nanofibers, respectively. Altogether, the present study demonstrates that the SPCNNs have good mechanical and thermal properties and appropriate potential for use in numerous thermal energy storage applications.
Polypyrrole‐Coated Magnetite Fe3O4 Nanoparticles Containing an Anthraquinone Crown Ether Macrocycle Used for the Extraction of Cu(II) Ion from Water
Authors: Bhowmick Arundhati , Weatherman Dasha , Kundu Patit Paban , Sykes Andrew G.
Published: February 2016

Uniform Fe3O4 nanoparticles (NPs) with an average crystallite size of 12 nm were rapidly prepared using a sonochemical route. These NPs were subsequently coated with a crown ether‐functionalized polypyrrole polymer. The morphology, structure, and composition of the coated and uncoated NPs were characterized by elemental analyses, transmission electronic microscopy, X‐ray powder diffraction, and Fourier transform infrared spectroscopy. The resultant nanocomposites possess the magnetism of Fe3O4 NPs that make for easy separation by an external magnetic field and show the ability to remove Cu(II) from aqueous solution.
Organic Multilevel Memory Devices of Long‐Term Environmental Stability via Incorporation of Fluorine
Authors: Liu Zhaojun , He Jinghui , Li Hua , Xu Qingfeng , Li Najun , Chen Dongyun , Wang Lihua , Chen Xiaofang , Zhang Keqin , Lu Jianmei
Published: February 2016

Organic resistive memory devices have been considered as potential candidates for next‐generation, non‐volatile memories. As prerequisites for real applications such memory devices would need to attain a high storage density, low power consumption, and, especially, long‐term stability. Although extensive research has been carried out these issues have thus far not been resolved in a satisfactory manner. In this work, two phenothiazine‐cored, cyano‐substituted diphenylethene derivatives with trifluoromethyl and nitro‐groups (PTZ‐CF3 and PTZ‐NO2) are presented and the performance of electroresistive memory devices based on these two molecules is investigated. Both molecules can realize ternary memory data storage with ternary device yields as high as 70%. In addition, PTZ‐CF3‐based devices exhibit a long‐term stability (up to three months), lower operating voltage (−1.01/−2.42 V), and higher ON/OFF ratios (>104 and 103) compared to those based on PTZ‐NO2. Such superior performance can be attributed to the introduced trifluoromethyl group, which leads to a better solubility, film‐forming ability, and hydrophobicity. These results may serve as a guide to improve the performance and promote the development of organic memories.
Tatton–Brown–Rahman syndrome due to 2p23 microdeletion
Authors: Okamoto Nobuhiko , Toribe Yasuhisa , Shimojima Keiko , Yamamoto Toshiyuki
Published: February 2016

Tatton–Brown–Rahman syndrome is a new overgrowth syndrome due to DNMT3A (DNA cytosine 5 methyltransferase 3A) mutations. Mutation carriers show a distinctive facial appearance, intellectual disability, and increased height. We report a patient with overgrowth who showed submicroscopic deletion of chromosome 2p23 including DNMT3A. The deletion was detected by array‐CGH. He showed moderate ID and distinctive facial gestalt. His clinical features were consistent with those of Tatton–Brown–Rahman syndrome. We suggest that 2p23 microdeletion including DNMT3A may cause similar symptoms in patients with DNMT3A mutations and should be considered in patients with overgrowth. © 2016 Wiley Periodicals, Inc.
Novel myopathy in a newborn with Shwachman–Diamond syndrome and review of neonatal presentation
Authors: Topa Alexandra , Tulinius Mar , Oldfors Anders , Hedberg‐Oldfors Carola
Published: February 2016

Shwachman–Diamond–Bodian syndrome (SDS) is a pleiotropic disorder in which the main features are bone marrow dysfunction and pancreatic insufficiency. Skeletal changes can occur, and in rare cases manifest as severe congenital thoracic dystrophy. We report a newborn boy with asphyxia, narrow thorax, and severe hypotonia initially suggesting a neuromuscular disease. The muscle biopsy showed myopathic changes with prominent variability in muscle fiber size and abnormal expression of developmental isoforms of myosin. The myofibrils showed focal loss and disorganization of myofilaments, and thickening of the Z‐discs including some abortive nemaline rods. The boy became permanently dependent on assisted ventilation. Pancreatic insufficiency was subsequently diagnosed, explaining the malabsorption and failure to thrive. Except transitory thrombocytopenia and leukopenia, no major hematological abnormalities were noted. He had bilateral nephrocalcinosis with preserved renal function. Transitory liver dysfunction with elevated transaminase levels and parenchymal changes on ultrasound were registered. The clinical diagnosis was confirmed by detection of compound heterozygous mutations in SBDS using whole‐exome sequencing: a recurrent intronic mutation causing aberrant splicing (c.258+2T>C) and a novel missense variant in a highly conserved codon (c.41A>G, p.Asn14Ser), considered to be damaging for the protein structure by in silico prediction programs. The carrier status of the parents has been confirmed. This case illustrates the challenges in differential diagnosis of pronounced neonatal hypotonia with asphyxia and highlights the muscular involvement in SDS. To our knowledge, this is the first report of myopathy evidenced in a patient with clinically and molecularly confirmed SDS. © 2016 Wiley Periodicals, Inc.
Prenatal detection of 5q14.3 duplication including MEF2C and brain phenotype
Authors: Cesaretti Claudia , Spaccini Luigina , Righini Andrea , Parazzini Cecilia , Conte Giorgio , Crosti Francesca , Redaelli Serena , Bulfamante Gaetano , Avagliano Laura , Rustico Mariangela
Published: February 2016

The 5q14.3 duplication is a rare condition comprising speech and developmental delay, microcephaly, and mild ventriculomegaly. The region 5q14.3 contains several genes but the predominant role for the onset of the neurodevelopmental phenotype has been attributed to MEF2C. We describe the prenatal identification of 5q14.3 duplication, including MEF2C, in a monochorionic twin pregnancy with corpus callosum anomalies, confirmed by autopsy. To the best of our knowledge, this cerebral finding has been observed for the first time in 5q14.3 duplication patients, possibly widening the neurological picture of this scarcely known syndrome. A pathogenetic role of MEF2C overexpression in brain development may be assumed, but further studies are needed. © 2016 Wiley Periodicals, Inc.
Cortical bone histomorphology of known‐age skeletons from the Kirsten collection, Stellenbosch university, South Africa
Authors: Pfeiffer Susan , Heinrich Jarred , Beresheim Amy , Alblas Mandi
Published: February 2016

Objectives

Normal human bone tissue changes predictably as adults get older, but substantial variability in pattern and pace remains unexplained. Information is needed regarding the characteristics of histological variables across diverse human populations.

Methods

Undecalcified thin sections from mid‐thoracic ribs of 213 skeletons (138 M, 75 F, 17–82 years, mean age 48 years), are used to explore the efficacy of an established age‐at‐death estimation method and methodological approach (Cho et al.: J Forensic Sci 47 (2002) 12‐18) and expand on it. The ribs are an age‐balanced sample taken from skeletonized cadavers collected from 1967 to 1999 in South Africa, each with recorded sex, age, cause of death and government‐defined population group (129 “Colored,” 49 “Black,” 35 “White”).

Results

The Ethnicity Unknown equation performs better than those developed for European‐Americans and African‐Americans, in terms of accuracy and bias. A new equation based solely on the study sample does not improve accuracy. Osteon population densities (OPD) show predicted values, yet secondary osteon areas (On.Ar) are smaller than expected for non‐Black subgroups. Relative cortical area (Ct.Ar/Tt.Ar) is low among non‐Whites.

Conclusions

Results from this highly diverse sample show that population‐specific equations do not increase estimate precision. While within the published range of error for the method (±24.44 years), results demonstrate a systematic under‐aging of young adults and over‐aging of older adults. The regression approach is inappropriate. The field needs fresh approaches to statistical treatment and to factors behind cortical bone remodeling. Am J Phys Anthropol 160:137–147, 2016. © 2016 The Authors American Journal of Physical Anthropology Published by Wiley Periodicals, Inc.
Pyrone Diels–Alder Routes to Indolines and Hydroindolines: Syntheses of Gracilamine, Mesembrine, and Δ7‐Mesembrenone
Authors: Gan Pei , Smith Myles W. , Braffman Nathaniel R. , Snyder Scott A.
Published: February 2016

Although the Diels–Alder reaction has long been utilized for the preparation of numerous heterocycles, opportunities to extend its power remain. Herein, we detail a simple, modular, and robust approach that combines various amines regioselectively with 4,6‐dichloropyrone to create substrates which, under appropriate conditions, can directly deliver varied indolines and hydroindolines through [4+2] cycloadditions with substitution patterns difficult to access otherwise. As an initial demonstration of the power of the strategy, several different natural products have been obtained either formally or by direct total synthesis, with efforts toward one of these—the complex amaryllidaceae alkaloid gracilamine—affording the shortest route to date in terms of linear step count.
Polysiloxane microspheres functionalized with imidazole groups as a palladium catalyst support
Authors: Pospiech Piotr , Chojnowski Julian , Mizerska Urszula , Makowski Tomasz , Strzelec Krzysztof , Sienkiewicz Natalia
Published: February 2016

Polysiloxane microspheres containing a large number of silanol groups were obtained by an emulsion process of modified polyhydromethylsiloxane. N‐substituted imidazole groups were grafted on these microspheres by the silylation of their silanol groups with N‐[γ‐(dimethylchlorosilyl)propyl]imidazole hydrochloride. The progress of the reaction was monitored using 29Si and 13C magic angle spinning (MAS) NMR and its impact on microsphere morphology was studied using scanning electron microscopy (SEM). The usefulness of the imidazole‐functionalized microspheres as a support for a metal catalyst was demonstrated by their reaction with PdCl2(PhCN)2. In this way a new heterogenized catalyst, Pd(II) complex with imidazole ligands supported on polysiloxane microspheres, was generated. This catalyst, MPd, was characterized using 13C and 29Si MAS NMR, X‐ray photoelectron, Fourier transform infrared and far‐infrared spectroscopies, X‐ray diffraction, SEM–energy‐dispersive X‐ray spectroscopy and wide‐angle X‐ray scattering. The catalyst appears in two structures, as Pd(II) complex and Pd(0) nanoclusters. Its catalytic activity was tested using a model reaction, the hydrogenation of cinnamaldehyde, and compared with that of an analogous complex operating in a homogeneous system. MPd showed a high activity in the promotion of hydrogenation of cinnamaldehyde. The activity in the substrate conversion was stable at least in five cycles of this reaction. The main product was hydrocinnamaldehyde which could be obtained with a yield above 70%. A mechanism of the reaction is proposed. Copyright © 2016 John Wiley & Sons, Ltd.
Thermoplastic polyvinyl alcohol/multiwalled carbon nanotube composites: Preparation, mechanical properties, thermal properties, and electromagnetic shielding effectiveness
Authors: Lin Jia‐Horng , Lin Zheng‐Ian , Pan Yi‐Jun , Hsieh Chien‐Teng , Huang Chien‐Lin , Lou Ching‐Wen
Published: February 2016

This study uses the solution mixing method to combine plasticized polyvinyl alcohol (PVA) as a matrix, and multiwalled carbon nanotubes (MWCNTs) as reinforcement to form PVA/MWCNTs films. The films are then laminated and hot pressed to create PVA/MWCNTs composites. The control group of PVA/MWCNTs composites is made by incorporating the melt compounding method. Diverse properties of PVA/MWCNTs composites are then evaluated. For the experimental group, the incorporation of MWCNTs improves the glass transition temperature (Tg), crystallization temperature, Tc), and thermal stability of the composites. In addition, the test results indicate that composites containing 1.5 wt % of MWCNTs have the maximum tensile strength of 51.1 MPa, whereas composites containing 2 wt % MWCNTs have the optimal electrical conductivity of 2.4 S/cm, and electromagnetic shielding effectiveness (EMI SE) of −31.41 dB. This study proves that the solution mixing method outperforms the melt compounding method in terms of mechanical properties, dispersion, melting and crystallization behaviors, thermal stability, and EMI SE. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43474.
Brief Report: Intensification to Triple Therapy After Treatment With Nonbiologic Disease‐Modifying Antirheumatic Drugs for Rheumatoid Arthritis in the United States From 2009 to 2014
Authors: Sparks Jeffrey A. , Krumme Alexis A. , Shrank William H. , Matlin Olga S. , Brill Gregory , Pezalla Edmund J. , Choudhry Niteesh K. , Solomon Daniel H.
Published: February 2016

Objective

Several trials suggest that triple therapy (methotrexate, sulfasalazine, and hydroxychloroquine) and biologic disease‐modifying antirheumatic drugs (DMARDs) have similar efficacy in patients with rheumatoid arthritis (RA). This study was undertaken to investigate intensification to triple therapy after initial nonbiologic prescription among patients with RA.

Methods

The use of triple therapy among patients with RA in 2009–2014 was evaluated using US insurance claims data. Patients with a health care visit for RA and an initial nonbiologic DMARD prescription were included. Frequencies of intensification to triple therapy or a biologic DMARD and rates of intensification per 6‐month time period were calculated. Using Cox regression, we evaluated whether sociodemographic, temporal, geographic, clinical, and health care utilization factors were associated with intensification to triple therapy. Among those patients whose therapy was intensified, we investigated factors associated with triple therapy use by logistic regression. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) for intensification to triple therapy in relation to various clinical and demographic factors were calculated.

Results

There were 24,576 patients with a mean ± SD age of 50.3 ± 12.3 years, and 78% were female. During the study period, treatment was intensified to biologic DMARDs in 2,739 patients (11.1%) compared to 181 patients (0.7%) whose treatment was intensified to triple therapy. There was no significant change in triple therapy use across calendar years. Patients whose treatment was intensified to triple therapy were more likely to receive glucocorticoids (HR 1.91 [95% CI 1.41–2.60]) compared to patients who did not use glucocorticoids and were more likely to use nonsteroidal antiinflammatory drugs (NSAIDs) (HR 1.48, 95% CI 1.10–1.99 versus no NSAID use). Among those patients whose treatment was intensified to triple therapy or biologic DMARDs, factors significantly associated with triple therapy use included older age, US region (with the highest odds for triple therapy use in the West and lowest odds for triple therapy use in the Northeast), glucocorticoid use, and lower number of outpatient visits within 180 days of initial nonbiologic DMARD prescription.

Conclusion

Despite reports published during the study period suggesting equivalent efficacy of triple therapy and biologic DMARDs for RA, the use of triple therapy was infrequent and did not increase over time in this large nationwide study.
Aging Promotes Sirtuin 3–Dependent Cartilage Superoxide Dismutase 2 Acetylation and Osteoarthritis
Authors: Fu Yao , Kinter Michael , Hudson Joanna , Humphries Kenneth M. , Lane Rachel S. , White Jeremy R. , Hakim Michael , Pan Yong , Verdin Eric , Griffin Timothy M.
Published: February 2016

Objective

To quantify functional age‐related changes in the cartilage antioxidant network in order to discover novel mediators of cartilage oxidative stress and osteoarthritis (OA) pathophysiology.

Methods

We evaluated histopathologic changes of knee OA in 10‐, 20‐, and 30‐month‐old male F344BN rats and analyzed cartilage oxidation according to the ratio of reduced to oxidized glutathione. Antioxidant gene expression and protein abundance were analyzed by quantitative reverse transcription–polymerase chain reaction and selected reaction–monitoring mass spectrometry, respectively. Superoxide dismutase 2 (SOD2) activity and acetylation were analyzed by colorimetric enzyme assays and Western blotting, respectively. We examined human OA cartilage to evaluate the clinical relevance of SOD2 acetylation, and we tested age‐related changes in the mitochondrial deacetylase sirtuin 3 (SIRT‐3) in rats and mice.

Results

Cartilage oxidation and OA severity in F344BN rats increased with age and were associated with an increase in SOD2 expression and protein abundance. However, SOD2‐specific activity decreased with age due to elevated posttranslational lysine acetylation. Consistent with these findings, SIRT‐3 levels decreased substantially with age, and treatment with SIRT‐3 increased SOD2 activity in an age‐dependent manner. SOD2 was also acetylated in human OA cartilage, and activity was increased with SIRT‐3 treatment. Moreover, in C57BL/6J mice, cartilage SIRT‐3 expression decreased with age, and whole‐body deletion of SIRT‐3 accelerated the development of knee OA.

Conclusion

Our results show that SIRT‐3 mediates age‐related changes in cartilage redox regulation and protects against early‐stage OA. These findings suggest that mitochondrial acetylation promotes OA and that restoration of SIRT‐3 in aging cartilage may improve cartilage resistance to oxidative stress by rescuing acetylation‐dependent inhibition of SOD2 activity.
HLA–DPB1 as a Risk Factor for Relapse in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis: A Cohort Study
Authors: Hilhorst Marc , Arndt Fabian , Joseph Kemna Michael , Wieczorek Stefan , Donner Yoni , Wilde Benjamin , Thomas Epplen Jörg , van Paassen Pieter , Cohen Tervaert Jan Willem
Published: February 2016

Objective

The antineutrophil cytoplasmic antibody (ANCA)–associated vasculitides (AAVs) form a group of small‐vessel vasculitides with systemic involvement. Although the etiology of AAVs remains largely unknown, both genetic and environmental factors have been implicated. Recently, certain alleles in the HLA–DPB1 region on chromosome 6 were shown to be associated with proteinase 3 (PR3)–ANCA–positive AAV but not with myeloperoxidase (MPO)–ANCA–positive AAV. The aim of this study was to investigate whether different alleles in the HLA–DPB1 region have clinical and/or prognostic implications in AAV.

Methods

One hundred seventy‐four patients with a diagnosis of AAV were recruited at the Maastricht University Medical Centre between 2000 and 2009. Seventeen different HLA–DPB1 alleles were determined using the restriction fragment length polymorphism technique. A validation cohort of 170 AAV patients from the Vasculitis Centre of Luebeck/Bad Bramstedt was included.

Results

In the initial cohort, the distribution of HLA–DPB1 alleles was significantly different between PR3‐ANCA–positive compared with MPO‐ANCA–positive AAV patients, ANCA‐negative AAV patients, and healthy controls. Importantly, HLA–DPB1*04:01 was present in 90% of PR3‐ANCA–positive AAV patients compared with 63% of MPO‐ANCA–positive AAV patients, 58% of ANCA‐negative patients, and 63% of healthy controls. Patients homozygous for HLA–DPB1*04:01 had relapses more often compared with heterozygous patients and noncarrier patients. This association persisted after correction for ANCA subtype and diagnosis. In the validation cohort, patients homozygous for HLA–DPB1*04:01 and those heterozygous for HLA–DPB1*04:01 had relapses more often compared with noncarrier patients. When both patient cohorts were merged (n = 344), homozygous patients relapsed most often, followed by heterozygous patients and noncarrier patients.

Conclusion

Carriage of HLA–DPB1*04:01 in patients with AAV is significantly associated with an increased risk of relapse compared with HLA–DPB1*04:01–negative patients, irrespective of ANCA status or clinical AAV entity.
Mesenchymal Stem Cell Alterations in Bone Marrow Lesions in Patients With Hip Osteoarthritis
Authors: Campbell T. Mark , Churchman Sarah M. , Gomez Alejandro , McGonagle Dennis , Conaghan Philip G. , Ponchel Frederique , Jones Elena
Published: February 2016

Objective

In patients with osteoarthritis (OA), bone marrow lesions (BMLs) are intimately linked to disease progression. We hypothesized that aberrant multipotential stromal cell (also known as mesenchymal stem cell [MSC]) responses within bone tissue contributes to BML pathophysiology. The aim of this study was to investigate BML and non‐BML native subchondral bone MSCs for numeric, topographic, in vitro functional, and gene expression differences.

Methods

Ex vivo 3T magnetic resonance imaging (MRI) of the femoral heads of 20 patients with hip OA was performed. MRI‐determined BML and non‐BML regions were excised and enzymatically treated to extract cells and quantify MSCs using flow cytometry and colony‐forming unit–fibroblast (CFU‐F) assay. Immunohistochemical analysis was performed to determine in vivo CD271+ MSC distribution. Culture‐expanded CD271+ cells were analyzed for tripotentiality and gene expression.

Results

BML regions were associated with greater trabecular bone area and cartilage damage compared with non‐BML regions. The proportion of CD45−CD271+ MSCs was higher in BML regions compared with non‐BML regions (median difference 5.6‐fold; P < 0.001); the CFU‐F assay showed a similar trend (median difference 4.3‐fold; P = 0.013). Immunohistochemistry revealed CD271+ cell accumulation in bone adjacent to cartilage defects and areas of osteochondral angiogenesis. BML MSCs had lower proliferation and mineralization capacities in vitro and altered expression of TNFSF11/RANKL and CXCR4/stromal cell–derived factor 1 receptor. OA MSCs showed up‐regulated transcripts for CXCR1 and CCR6 compared with MSCs derived from healthy or osteoporotic bone.

Conclusion

This study is the first to show numeric and topographic alterations in native MSCs in the diseased bone of patients with hip OA. Given the associated functional perturbation of MSCs, these data suggest that subchondral bone MSC manipulation may be an OA treatment target.