bluuebunny/crossref_metadata_2025 huggingface dataset:
Are international differences in breast cancer survival between Australia and the UK present amongst both screen‐detected women and non‐screen‐detected women? survival estimates for women diagnosed in West Midlands and New South Wales 1997–2006
Authors: Woods Laura M. , Rachet Bernard , O'Connell Dianne L. , Lawrence Gill , Coleman Michel P.
Published: January 2016

We examined survival in screened‐detected and non‐screen‐detected women diagnosed in the West Midlands (UK) and New South Wales (Australia) in order to evaluate whether international differences in survival are related to early diagnosis, or to other factors relating to the healthcare women receive. Data for women aged 50 − 65 years who had been eligible for screening from 50 years were examined. Data for 5,628 women in West Midlands and 6,396 women in New South Wales were linked to screening service records (mean age at diagnosis 53.7 years). We estimated net survival and modelled the excess hazard ratio of breast cancer death by screening status. Survival was lower for women in the West Midlands than in New South Wales (5‐year net survival 90.9% [95% CI 89.9%−91.7%] compared with 93.4% [95% CI 92.6%‐94.1%], respectively). The difference was greater between the two populations of non‐screen‐detected women (4.9%) compared to between screen‐detected women, (1.8% after adjustment for lead‐time and over‐diagnosis). The adjusted excess hazard ratio of breast cancer death for West Midlands compared with New South Wales was greater in the non‐screen‐detected group (EHR 2.00, 95% CI 1.70 − 2.31) but not significantly different to that for women whose cancer had been screen‐detected (EHR 1.72, 95% CI 0.87 − 2.56). In this study more than one in three breast cancer deaths in the West Midlands would have been avoided if survival had been the same as in New South Wales. The possibility that women in the UK receive poorer treatment is an important potential explanation which should be examined with care.
Cathepsin L inactivation leads to multimodal inhibition of prostate cancer cell dissemination in a preclinical bone metastasis model
Authors: Sudhan Dhivya R. , Pampo Christine , Rice Lori , Siemann Dietmar W.
Published: January 2016

It is estimated that approximately 90% of patients with advanced prostate cancer develop bone metastases; an occurrence that results in a substantial reduction in the quality of life and a drastic worsening of prognosis. The development of novel therapeutic strategies that impair the metastatic process and associated skeletal adversities is therefore critical to improving prostate cancer patient survival. Recognition of the importance of Cathepsin L (CTSL) to metastatic dissemination of cancer cells has led to the development of several CTSL inhibition strategies. The present investigation employed intra‐cardiac injection of human PC‐3ML prostate cancer cells into nude mice to examine tumor cell dissemination in a preclinical bone metastasis model. CTSL knockdown confirmed the validity of targeting this protease and subsequent intervention studies with the small molecule CTSL inhibitor KGP94 resulted in a significant reduction in metastatic tumor burden in the bone and an improvement in overall survival. CTSL inhibition by KGP94 also led to a significant impairment of tumor initiated angiogenesis. Furthermore, KGP94 treatment decreased osteoclast formation and bone resorptive function, thus, perturbing the reciprocal interactions between tumor cells and osteoclasts within the bone microenvironment which typically result in bone loss and aggressive growth of metastases. These functional effects were accompanied by a significant downregulation of NFκB signaling activity and expression of osteoclastogenesis related NFκB target genes. Collectively, these data indicate that the CTSL inhibitor KGP94 has the potential to alleviate metastatic disease progression and associated skeletal morbidities and hence may have utility in the treatment of advanced prostate cancer patients.
The impact of balance‐focused attitudes on job stress: Gender differences evidenced in American and Chinese samples
Authors: Li Chenwei , Wu Keke (‘Coco’) , Johnson Diane E.
Published: January 2016

Based on gender role expectations model, we examined how balance‐focused attitudes would affect job stress by influencing individuals' perceptions of family interference with work (FIW), and investigated whether a gender difference would exist in the relationships among balance‐focused attitudes, FIW and job stress. Using two independent samples from the United States and China, we found support for the indirect influence of balance‐focused attitudes on job stress, through FIW. Participants with balance‐focused attitudes experienced lower levels of job stress as they perceived less interference from family to work. As expected, such indirect effect was more pronounce among male participants, meaning that the male participants benefited more from having balance‐focused attitudes. Discussion, theoretical and practical implications are provided.
Screening of PRKAR1A and PDE4D in a Large Italian Series of Patients Clinically Diagnosed With Albright Hereditary Osteodystrophy and/or Pseudohypoparathyroidism
Authors: Elli Francesca Marta , Bordogna Paolo , de Sanctis Luisa , Giachero Federica , Verrua Elisa , Segni Maria , Mazzanti Laura , Boldrin Valentina , Toromanovic Alma , Spada Anna , Mantovani Giovanna
Published: January 2016

The cyclic adenosine monophosphate (cAMP) intracellular signaling pathway mediates the physiological effects of several hormones and neurotransmitters, acting by the activation of G-protein coupled receptors (GPCRs) and several downstream intracellular effectors, including the heterotrimeric stimulatory G-protein (Gs), the cAMP-dependent protein kinase A (PKA), and cAMP-specific phosphodiesterases (PDEs). Defective G-protein–mediated signaling has been associated with an increasing number of disorders, including Albright hereditary osteodistrophy (AHO) and pseudohypoparathyroidism (PHP), a heterogeneous group of rare genetic metabolic disorders resulting from molecular defects at the GNAS locus. Moreover, mutations in PRKAR1A and PDE4D genes have been recently detected in patients with acrodysostosis (ACRDYS), showing a skeletal and endocrinological phenotype partially overlapping with AHO/PHP. Despite the high detection rate of molecular defects by currently available molecular approaches, about 30% of AHO/PHP patients still lack a molecular diagnosis, hence the need to screen patients negative for GNAS epi/genetic defects also for chromosomal regions and genes associated with diseases that undergo differential diagnosis with PHP. According to the growing knowledge on Gsα-cAMP signaling-linked disorders, we investigated our series of patients (n = 81) with a clinical diagnosis of PHP/AHO but negative for GNAS anomalies for the presence of novel genetic variants at PRKAR1A and PDE4D genes. Our work allowed the detection of 8 novel missense variants affecting genes so far associated with ACRDYS in 9 patients. Our data further confirm the molecular and clinical overlap among these disorders. We present the data collected from a large series of patients and a brief review of the literature in order to compare our findings with already published data; to look for PRKAR1A/PDE4D mutation spectrum, recurrent mutations, and mutation hot spots; and to identify specific clinical features associated with ACRDYS that deserve surveillance during follow-up. © 2016 American Society for Bone and Mineral Research.
Care team identification in the electronic health record: A critical first step for patient‐centered communication
Authors: Dalal Anuj K. , Schnipper Jeffrey L.
Published: January 2016

Patient‐centered communication is essential to coordinate care and safely progress patients from admission through discharge. Hospitals struggle with improving the complex and increasingly electronic conversation patterns among care team members, patients, and caregivers to achieve effective patient‐centered communication across settings. Accurate and reliable identification of all care team members is a precursor to effective patient‐centered communication and ideally should be facilitated by the electronic health record. However, the process of identifying care team members is challenging, and team lists in the electronic health record are typically neither accurate nor reliable. Based on the literature and on experience from 2 initiatives at our institution, we outline strategies to improve care team identification in the electronic health record and discuss potential implications for patient‐centered communication. Journal of Hospital Medicine 2016;11:381–385. © 2016 Society of Hospital Medicine
Weight‐based insulin dosing for acute hyperkalemia results in less hypoglycemia
Authors: Wheeler Dauria T. , Schafers Stephen J. , Horwedel Tim A. , Deal Eli N. , Tobin Garry S.
Published: January 2016

Hyperkalemia treatment with intravenous insulin has been associated with hypoglycemia. This single‐center, retrospective study compared the effects on hypoglycemia between weight‐based insulin dosing (0.1 U/kg of body weight up to a maximum of 10 U) compared to standard flat doses of 10 U among patients weighing less than 95 kg. Of the 132 charts randomly selected for review, hypoglycemic events (blood glucose <70 mg/dL) were reduced from 27.3% in the 10‐U group to 12.1% in the weight‐based group (P = 0.05). The number of affected patients was reduced with 19.7% in the 10‐U group and 10.6% in the weight‐based group (P = 0.22). The potassium‐lowering effects of these 2 strategies were similar between groups. Female patients and those with baseline glucose values <140 mg/dL were at increased risk for hypoglycemia. Weight‐based insulin dosing (0.1 U/kg) for acute hyperkalemia therapy resulted in less hypoglycemia without impacting potassium lowering. Journal of Hospital Medicine 2016;11:355–357. © 2016 Society of Hospital Medicine
Influence of fat on liver T1 measurements using modified Look–Locker inversion recovery (MOLLI) methods at 3T
Authors: Mozes Ferenc E. , Tunnicliffe Elizabeth M. , Pavlides Michael , Robson Matthew D.
Published: January 2016

Purpose

To characterize the effect of fat on modified Look–Locker inversion recovery (MOLLI) T1 maps of the liver. The balanced steady‐state free precession (bSSFP) sequence causes water and fat signals to have opposite phase when repetition time (TR) = 2.3 msec at 3T. In voxels that contain both fat and water, the MOLLI T1 measurement is influenced by the choice of TR.

Materials and Methods

MOLLI T1 measurements of the liver were simulated using the Bloch equations while varying the hepatic lipid content (HLC). Phantom scans were performed on margarine phantoms, using both MOLLI and spin echo inversion recovery sequences. MOLLI T1 at 3T and HLC were determined in patients (n = 8) before and after bariatric surgery.

Results

At 3T, with HLC in the 0–35% range, higher fat fraction values lead to longer MOLLI T1 values when TR = 2.3 msec. Patients were found to have higher MOLLI T1 at elevated HLC (T1 = 929 ± 97 msec) than at low HLC (T1 = 870 ± 44 msec).

Conclusion

At 3T, MOLLI T1 values are affected by HLC, substantially changing MOLLI T1 in a clinically relevant range of fat content. J. Magn. Reson. Imaging 2016;44:105–111.
Systematic evaluation of data‐independent acquisition for sensitive and reproducible proteomics—a prototype design for a single injection assay
Authors: Heaven Michael R. , Funk Adam J. , Cobbs Archie L. , Haffey Wendy D. , Norris Jeremy L. , McCullumsmith Robert E. , Greis Kenneth D.
Published: January 2016

Data‐independent acquisition (DIA)‐based proteomics has become increasingly complicated in recent years because of the vast number of workflows described, coupled with a lack of studies indicating a rational framework for selecting effective settings to use. To address this issue and provide a resource for the proteomics community, we compared 12 DIA methods that assay tryptic peptides using various mass‐isolation windows. Our findings indicate that the most sensitive single injection LC‐DIA method uses 6 m/z isolation windows to analyze the densely populated tryptic peptide range from 450 to 730 m/z, which allowed quantification of 4465 Escherichia coli peptides. In contrast, using the sequential windowed acquisition of all theoretical fragment‐ions (SWATH) approach with 26 m/z isolation windows across the entire 400–1200 m/z range, allowed quantification of only 3309 peptides. This reduced sensitivity with 26 m/z windows is caused by an increase in co‐eluting compounds with similar precursor values detected in the same tandem MS spectra, which lowers the signal‐to‐noise of peptide fragment‐ion chromatograms and reduces the amount of low abundance peptides that can be quantified from 410 to 920 m/z. Above 920 m/z, more peptides were quantified with 26 m/z windows because of substantial peptide 13C isotope distributions that parse peptide ions into separate isolation windows. Because reproducible quantification has been a long‐standing aim of quantitative proteomics, and is a so‐called trait of DIA, we sought to determine whether precursor‐level chromatograms used in some methods rather than their fragment‐level counterparts have similar precision. Our data show that extracted fragment‐ion chromatograms are the reason DIA provides superior reproducibility. Copyright © 2015 John Wiley & Sons, Ltd.
Movement impairment: Focus on the brain
Authors: Adami Raffaella , Bottai Daniele
Published: January 2016

The saying “mens sana in corpore sano” has a particular resonance these days because, for the majority who have a very sedentary occupation, the everyday rhythms of life do not compel us to do much physical exercise. Recently published data indicate that exercise can counteract the effects of neurological diseases such as Alzheimer's disease and have prompted research on the beneficial effects of movement on the brain and brain neurogenesis. This might lead us to hypothesize that the absence or reduction of movements, especially those with antigravity effects, could induce a deterioration of the brain. This Review discusses current knowledge of the relationship between neurogenic capacity and the lack of motor activity in human and animal models. © 2016 Wiley Periodicals, Inc.
A deglaciation model of the Oberhasli, Switzerland
Authors: Wirsig Christian , Zasadni Jerzy , Ivy‐Ochs Susan , Christl Marcus , Kober Florian , Schlüchter Christian
Published: January 2016

We combine 10Be surface exposure ages from boulders and bedrock, field observations and measurement of bedrock ice‐flow direction indicators with numerical ice surface models to develop a model of the evolution of the Oberhasli area in the central Swiss Alps from the Last Glacial Maximum (LGM) to the early Holocene. Surface exposure ages from bedrock and boulder samples imply that the highest ice surface at the glacial trimline in Haslital was attained at 23.0 ± 0.8 ka. Significant retreat followed no later than 17.7 ± 0.8 ka. Several boulders were let down on the Gelmerhörner ridge during lowering of the ice surface of the Aare LGM glacier. Their exposure ages of 16–14 ka suggest that patches of remnant ice persisted on the trough shoulder until the Bølling–Allerød interstadial. Lateglacial glacier systems in the High Alps were of a dendritic character, confined to the trunk valleys and cirques. Based on combined evidence from glacial erosional marks, surface exposure ages and numerical modelling we have been able to constrain the likely terminal position and ice surface of the Egesen stadial glacier (Younger Dryas equivalent) in Haslital. Exposure ages from the trough floor imply that deglaciation was completed at the end of the Younger Dryas at 12.2–10.8 ka.
Rising waters and processes of diversification and unification in material culture: the flooding of Doggerland and its effect on north‐west European prehistoric populations between ca. 13 000 and 1500 cal BC
Authors: Ballin Torben Bjarke
Published: January 2016

The present paper discusses how post‐glacial sea level rises may have led to material cultural diversification and ‘atomization’ of geographically extensive cultures or social territories. The resulting smaller social territories, with their associated material cultures, subsequently began to merge, possibly due to the development of better means of transport. Where the North Sea, at the beginning of this process of material diversification, represented a growing barrier to contacts, it later became a means of communication. In this paper, dates for material cultures follow those of Vang Petersen ().
Examining Minority Attrition Among Women in Longitudinal Trauma Research
Authors: Boykin Derrecka M. , London Melissa J. , Orcutt Holly K.
Published: January 2016

Research suggests that racial and ethnic minorities are more likely to attrit from longitudinal trauma studies than non‐Hispanic Whites. Yet, little is known about how the loss of minority participants influences longitudinal findings as well as internal and external validity of study findings. Thus, the present study examined the effects of race/ethnicity on attrition in a longitudinal trauma study of women (minority = 223, non‐Hispanic White or majority = 459) exposed to a campus shooting. Survival analyses were used to compare the attrition rates of minority participants to majority participants and assess the extent to which race/ethnicity, among other variables, predicted attrition. Minority participants were more likely to attrit than majority participants, hazard ratio (HR) = 0.69, 95% CI [0.48, 0.99], even after adjusting for study variables. A main effect was also found for age, HR = 1.06, 95% CI [1.01, 1.12]. Race/ethnicity did not interact with other study variables to influence attrition. The findings underscored the importance of assessing the effects of attrition on longitudinal findings and external validity.
Tidal benthic mesocosms simulating future climate change scenarios in the field of marine ecology
Authors: Pansch Andreas , Winde Vera , Asmus Ragnhild , Asmus Harald
Published: January 2016

Increasing human activities cause local to global changes in sea surface temperatures, ocean acidity, eutrophication, and rising sea levels. Many laboratory experiments investigate the effects of these regime shifts on single species and single stressors, showing variable responses within and among species, while different combinations of stressors can have synergistic, additive or antagonistic effects. Large‐scale multi‐species and multi‐stressor experiments can more reliably predict future ecosystem changes. A unique mesocosm facility was developed and set up at the AWI Wadden Sea Station – Sylt, Northern Germany to investigate the particular effects of future climate changes on predominant marine intertidal communities. Each of 12 benthic mesocosms serves as an independent experimental unit with novel techniques of tide and current simulations as well as multi parameter measurement systems to simulate multi‐factorial climate change scenarios including the combination of warming, acidification, nutrient enrichment, and sea level rise. Temperature, pH, oxygen, and salinity can be continuously monitored and logged, while discretely collected samples of total alkalinity, light availability, chlorophyll a (Chl a), nutrients and seston supplement these online datasets. Herein we demonstrate the functionality of the new benthic mesocosm system including first experimental results on the responses of Fucus vesiculosus forma mytili, and its associated community to the combination of warming, ocean acidification, and increased nutrient enrichment.
Near‐IR image‐guided laser ablation of demineralization on tooth occlusal surfaces
Authors: Tom Henry , Chan Kenneth H. , Darling Cynthia L. , Fried Daniel
Published: January 2016

Introduction

Studies have shown that reflectance images at near‐IR wavelengths coincident with higher water absorption are well‐suited for image‐guided laser ablation of carious lesions since the contrast between sound and demineralized enamel is extremely high and interference from stains is minimized. The objective of this study was to demonstrate that near‐IR reflectance images taken at a wavelength range of 1,500–1,700 nm can be used to guide a 9.3 μm CO2 laser for the selective ablation of early demineralization on tooth occlusal surfaces.

Methods

The occlusal surfaces of ten sound human molars were used in this in vitro study. Shallow simulated caries lesions with random patterns and varying depth and position were produced on tooth occlusal surfaces. Sequential near‐IR reflectance images at 1,500–1,700 nm were used to guide the laser for the selective removal of the demineralized enamel. Digital microscopy and polarization sensitive optical coherence tomography (PS‐OCT) were used to assess selectivity.

Results

Images taken before and after lesion removal suggest that the demineralized areas were removed with high selectivity. Although the estimated volume of tissue ablated was typically higher than the initial lesion volume measured with PS‐OCT, the volume of enamel removed by the laser correlated well with the initial lesion volume.

Conclusion

Sequential near‐IR reflectance images at 1,500–1,700 nm can be used to guide a 9.3 μm CO2 laser for the selective ablation of early demineralization on tooth occlusal surfaces. Lasers Surg. Med. 48:52–61, 2016. © 2016 Wiley Periodicals, Inc.
Amphiphilic Copolymers Shuttle Drugs Across the Blood–Brain Barrier
Authors: Clemens‐Hemmelmann Mirjam , Kuffner Christiane , Metz Verena , Kircher Linda , Schmitt Ulrich , Hiemke Christoph , Postina Rolf , Zentel Rudolf
Published: January 2016

Medical treatment of diseases of the central nervous system requires transport of drugs across the blood–brain barrier (BBB). Here, it is extended previously in vitro experiments with a model compound to show that the non‐water‐soluble and brain‐impermeable drug domperidone (DOM) itself can be enriched in the brain by use of an amphiphilic copolymer as a carrier. This carrier consists of poly(N‐(2‐hydroxypropyl)‐methacrylamide), statistically copolymerized with 10 mol% hydrophobic lauryl methacrylate, into whose micellar aggregates DOM is noncovalently absorbed. As tested in a BBB model efficient transport of DOM across, the BBB is achievable over a wide range of formulations, containing 0.8 to 35.5 wt% domperidone per copolymer. In neither case, the polymer itself is translocated across the BBB model. In vivo experiments in mice show that already 10 min after intraperitoneal injection of the polymer/domperidone (PolyDOM) formulation, domperidone can be detected in blood and in the brain. Highest serum and brain levels of domperidone are detected 40 min after injection. At that time point serum domperidone is increased 48‐fold. Most importantly, domperidone is exclusively detectable in high amounts in the brain of PolyDOM injected mice and not in mice injected with bare domperidone.

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Effect of PCL/PEG‐Based Membranes on Actinorhodin Production in Streptomyces coelicolor Cultivations
Authors: Scaffaro Roberto , Lopresti Francesco , Sutera Alberto , Botta Luigi , Fontana Rosa Maria , Puglia Anna Maria , Gallo Giuseppe
Published: January 2016

The actinomycetes, Gram‐positive filamentous bacteria, are the most prolific source of natural occurring antibiotics. At an industrial level, antibiotics from actinomycete strains are produced by means of submerged fermentations, where one of the major factors negatively affecting bioproductivity is the pellet‐shaped biomass growth. The immobilization of microorganisms on properly chosen supports prevents cell–cell aggregation resulting in improving the biosynthetic capability. Thus, novel porous biopolymer‐based devices are developed by combining melt mixing and particulate leaching. In particular, polycaprolactone (PCL), polyethylene glycol (PEG), and sodium chloride (NaCl) with different grain sizes are used to prepare PCL/PEG/NaCl blends in the melt. These blends are then leached to obtain PCL‐based porous membranes that are used as solid support for the growth of Streptomyces coelicolor, a model streptomycete used to produce various antibiotics including the blue colored actinorhodin (ACT). Thereafter, the effect of the devices' characteristics on the bacterial growth and on the production ACT is evaluated. The results showed that ACT production is strongly dependent on the pore size distribution of the device. Moreover, membranes with pores ranging from 90 to 110 μm are able to offer a potential improvement in volumetric productivity of ACT if compared to conventional submerged liquid culture.

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Effect of Dissolved Polymer on the Elasticity and Plasticity of a Lyotropic Lamellar Mesophase
Authors: Herrmann Laure , Kékicheff Patrick
Published: January 2016

Using the Surface Force Apparatus (SFA) technique, direct force–distance measurements between mica surfaces immersed in a polymer‐doped lamellar phase are presented. In the aqueous layers separating the charged and undulating bilayers of sodium dodecyl sulfate (SDS)/octanol, water is replaced by a polyethylene glycol aqueous solution (PEG,Mw20000 g/mol). As the mesophases align with the layers parallel to the solid mica surfaces the measurements yield structural information on the confined mesophases as well as bulk elastic properties. Keeping the membrane volume fraction constant the PEG dissolution results in a marked decrease in the elastic compressibility modulus,. This indicates a softening of the repulsive interactions between the lamellae mediated by polymer adsorption on the bilayers/aqueous solution interface. Insights into the behavior of the mesophases in confined geometries and thereby their stabilization mechanism are gained by noting a plastic contribution due to the presence of edge dislocations in the wedge‐like confinement geometry.
SVD analysis of Array transmission and reception and its use for bootstrapping calibration
Authors: Brunner David O. , Pruessmann Klaas P.
Published: January 2016

Purpose

Noise‐optimal reconstruction of array transmitter calibrations would ideally require knowledge of the receive array sensitivities which can often only be measured once the transmitter is calibrated to provide sufficient coverage. This poses often a problem in bootstrapping transmit‐receive arrays particularly at ultrahigh fields.

Methods

Said problem is resolved by formulating the local transmit‐receive efficiency of the array setup as a bilinear form and deriving therefrom a noise‐optimal, joint reconstruction of the calibration data resulting in the relative sensitivities of the used transmitters and receivers.

Results

Retrieval and reconstruction of parallel transmission calibration data in phantoms and in vivo are presented using an eight‐channel parallel transmit setup with up to 16 receivers using strip‐line TR arrays and parallel transmission by traveling waves.

Conclusion

Data sets from calibration scans are reconstructed robustly and with optimal signal‐to‐noise ratio. The found array signal gain is furthermore a direct performance measure for array transmitter and receiver combinations. The concomitantly obtained image was shown to have maximum coverage of the subject. Magn Reson Med 76:1730–1740, 2016. © 2016 International Society for Magnetic Resonance in Medicine
Polyacrylonitrile solution homogeneity study by dynamic shear rheology and the effect on the carbon fiber tensile strength
Authors: Newcomb Bradley A. , Gulgunje Prabhakar V. , Liu Yaodong , Gupta Kishor , Kamath Manjeshwar G. , Pramanik Chandrani , Ghoshal Sushanta , Chae Han Gi , Kumar Satish
Published: January 2016

Poly(acrylonitrile‐co‐methacrylic acid) (PAN‐co‐MAA)/N,N‐dimethylformamide (DMF) solutions were prepared and dynamic shear rheology of these solutions were investigated. With increasing stirring time up to 72 h at 70°C, the polymer solution became less elastic (more liquid‐like) with a ∼60% reduction in the zero‐shear viscosity. Relaxation spectra of the PAN‐co‐MAA/DMF solutions yield a decrease in relaxation time (disentanglement time, τd), corresponding to an about 8% decrease in viscosity average molecular weight. The log‐log plot of G′ (storage modulus) versus G″ (loss modulus) exhibited an increase in slope as a function of stirring time, suggesting that the molecular level solution homogeneity increased. In order to study the effect of solution homogeneity on the resulting carbon fiber tensile strength, multiple PAN‐co‐MAA/DMF solutions were prepared, and the precursor fibers were processed using gel‐spinning, followed by continuous stabilization and carbonization. The rheological properties of each solution were also measured and correlated with the tensile strength values of the carbon fibers. It was observed that with increasing the slope of the G′ versus G″ log‐log plot from 1.471 to 1.552, and reducing interfilament fiber friction during precursor fiber drawing through the addition of a fiber washing step prior to fiber drawing, the carbon fiber strength was improved (from 3.7 to 5.8 GPa). This suggests that along with precursor fiber manufacturing and carbonization, the solution homogeneity is also very important to obtain high strength carbon fiber. POLYM. ENG. SCI., 56:361–370, 2016. © 2016 Society of Plastics Engineers
Enabling Shared Leadership in Virtual Project Teams: A Practitioners’ Guide
Authors: Hoegl Martin , Muethel Miriam
Published: January 2016

Many virtual project teams perform better when leadership is shared (rather than centralized with the formal team leader); however, team leaders are often neither prepared to identify shared leadership potential nor to actually share leadership responsibility. Based on a study of 96 globally dispersed software development teams we show that team leaders tend to underestimate the team members’ capacity to lead themselves. As a consequence, these leaders monopolize decision-making authority and provide insufficient levels of autonomy for team members to tackle their tasks. Preventing the team members from unfolding their true potential, these leaders unconsciously jeopardize virtual team performance. Paradoxically, it is thus team leaders themselves hindering leadership effectiveness in virtual teams.
Enablers for Organizational Project Management in the Chinese Context
Authors: Wen Qi , Qiang Maoshan
Published: January 2016

This study aims at exploring the organizational enablers (OEs) for organizational project management (OPM) in the Chinese context. From the resource-based view of firms, we conceptualize OEs as important drivers for the business value creation processes in project-based organizations. The preliminary factor framework was constructed through literature review and expert interviews. Questionnaire surveys elicited 146 responses from Chinese project management practitioners; thereafter, factor analysis was performed to test the OE system empirically. The resulting final OE system contains 49 enablers in nine categories for three management hierarchies; this OE system, constructed by exploratory analysis and verified by confirmatory analysis, comprehensively clarifies the framework of OEs in the Chinese context; it facilitates further investigations into the interaction among OEs and their effects on organization performance. Firm managers may also find this system helpful in formulating identifiable, measurable, and manageable OE frameworks for their own firms, and enabling their organization's strategies with robust OEs.
3D V3O7·H2O/Partially Exfoliated Carbon Nanotube Composites with Significantly Improved Lithium Storage Ability
Authors: Zhang Xiyue , Yu Minghao , Zhao Shaobin , Li Feng , Hu Xianlei , Guo Shoubin , Lu Xihong , Tong Yexiang
Published: January 2016

Currently, transition metal oxides are widely explored as electrode materials for lithium ion batteries due to their remarkably large reversible capacities. However, these materials always suffer from poor conductivities and slow lithium ion diffusion in the lattice. Given this, a distinctive 3D porous network is developed through partial exfoliation of multiwall carbon nanotubes, which can function as not only superior conductive additive but also as an efficient 3D porous scaffold. By self‐assembling with V3O7·H2O nanowires, the hybrid electrode is demonstrated to achieve a significant boost in lithium storage when compared with pristine V3O7·H2O nanowires. This method can provide much inspiration in the construction of high‐performance metal oxides based electrodes.
Preclinical pharmacology and pharmacokinetics of CERC‐301, a GluN2B‐selective N‐methyl‐D‐aspartate receptor antagonist
Authors: Garner Rachel , Gopalakrishnan Shobha , McCauley John A. , Bednar Rodney A. , Gaul Stanley L. , Mosser Scott D. , Kiss Laszlo , Lynch Joseph J. , Patel Shil , Fandozzi Christine , Lagrutta Armando , Briscoe Richard , Liverton Nigel J. , Paterson Blake M. , Vornov James J. , Mazhari Reza
Published: January 2016

The preclinical pharmacodynamic and pharmacokinetic properties of 4‐methylbenzyl (3S, 4R)‐3‐fluoro‐4‐[(Pyrimidin‐2‐ylamino) methyl] piperidine‐1‐carboxylate (CERC‐301), an orally bioavailable selective N‐methyl‐D‐aspartate (NMDA) receptor subunit 2B (GluN2B) antagonist, were characterized to develop a translational approach based on receptor occupancy (RO) to guide CERC‐301 dose selection in clinical trials of major depressive disorder. CERC‐301 demonstrated high‐binding affinity (Ki, 8.1 nmol L−1) specific to GluN2B with an IC50 of 3.6 nmol L−1 and no off‐target activity. CERC‐301 efficacy was demonstrated in the forced swim test with an efficacy dose (ED50) of 0.3–0.7 mg kg−1 (RO, 30–50%); increase in locomotor activity was observed at ED50 of 2 mg kg−1, corresponding to an RO of 75%. The predicted 50% RO concentration (Occ50) in humans was 400 nmol L−1, similar to that predicted for rat, dog, and monkey (300, 200, and 400 nmol L−1, respectively). Safety pharmacology and neurotoxicity studies raised no specific safety concerns. A first‐in‐human study in healthy males demonstrated a dose‐proportional pharmacokinetic profile, with Tmax of ~1 h and t1/2 of 12–17 h. Based on the preclinical and pharmacodynamic data, doses of ≥8 mg in humans are hypothesized to have an acceptable safety profile and result in clinically relevant peak plasma exposure.
Bioequivalence of saxagliptin/dapagliflozin fixed‐dose combination tablets compared with coadministration of the individual tablets to healthy subjects
Authors: Vakkalagadda Blisse , Vetter Marion L. , Rana Jignasa , Smith Charles H. , Huang Jian , Karkas Jennifer , Boulton David W. , LaCreta Frank
Published: January 2016

Saxagliptin and dapagliflozin are individually indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. The bioequivalence of saxagliptin/dapagliflozin 2.5/5 mg and 5/10 mg fixed‐dose combination (FDC) tablets compared with coadministration of the individual tablets and the food effect on both strengths of saxagliptin/dapagliflozin FDCs were evaluated in this open‐label, randomized, single‐dose crossover study. Healthy subjects were randomized to saxagliptin 2.5 mg + dapagliflozin 5 mg fasted, 2.5/5 mg FDC fasted, 2.5/5 mg FDC fed (Cohort 1) or saxagliptin 5 mg + dapagliflozin 10 mg fasted, 5/10 mg FDC fasted, 5/10 mg FDC fed (Cohort 2). Serial blood samples for pharmacokinetics of saxagliptin and dapagliflozin were obtained predose and up to 60 h postdose. Bioequivalence of FDC tablets versus individual components was concluded if the 90% CIs for FDC to individual component geometric mean ratios of Cmax, AUC0‐T, and AUCinf of both analytes were between 0.80 and 1.25. Seventy‐two subjects were randomized; 71 (98.6%) completed the study. Saxagliptin/dapagliflozin 2.5/5 mg and 5/10 mg FDC tablets were bioequivalent to the individual tablets administered concomitantly. Food had no clinically meaningful effect on saxagliptin or dapagliflozin overall systemic exposure. Saxagliptin/dapagliflozin FDC tablets were bioequivalent to coadministration of the individual components in healthy subjects under fasted conditions and food had no clinically meaningful effect on bioavailability.
Formation of silicene on silver: Strong interaction between Ag and Si
Authors: Prévot Geoffroy , Bernard Romain , Cruguel Hervé , Curcella Alberto , Lazzeri Michele , Leoni Thomas , Masson Laurence , Ranguis Alain , Borensztein Yves
Published: January 2016

The real‐time formation of Si single layers on Ag(110) and Ag(111) has been investigated at different temperatures, by a combination of scanning tunnelling microscopy, grazing incidence X‐ray diffraction, optical differential reflectance spectroscopy and density functional theory. It is shown that the reactivity of the Ag substrate with the Si atoms is important. The formation of Si nanoribbons on Ag(110) is accompanied by a missing‐row reconstruction of the Ag surface, and the removed Ag atoms form additional islands. The mechanism of Si island formation on Ag(111) involves the insertion of single Si atoms within the Ag top layer and the exchange with Ag atoms. The released Ag atoms diffuse to steps edges and form new Ag fingers. This strong interaction between Si and Ag atoms with possible alloying, questions the actual structures of the different Si phases observed on Ag(110) and Ag(111), and usually attributed to silicene single layers.
Determination of bisphenol A‐glucuronide in human urine using ultrahigh‐pressure liquid chromatography/tandem mass spectrometry
Authors: Hauck Zane Z. , Huang Ke , Li Guannan , van Breemen Richard B.
Published: January 2016

Rationale

Used widely as a plasticizer and as a monomer for plastics, bisphenol A (BPA) is under investigation as a possible endocrine disrupter. As an indication of systemic exposure, a fast and accurate assay was developed for the major BPA metabolite in human urine, BPA‐monoglucuronide (BPA‐G), using ultrahigh‐pressure liquid chromatography/tandem mass spectrometry (UHPLC/MS/MS).

Methods

Urine samples were prepared using solid‐phase mixed‐mode reversed‐phase/anion‐exchange extraction. BPA‐G was measured using UHPLC/MS/MS with an amide UHPLC column interfaced to a triple‐quadrupole mass spectrometer equipped with negative ion electrospray, collision‐induced dissociation and selected reaction monitoring. [13C12]‐BPA‐G was used as a surrogate standard.

Results

By measuring the glucuronide metabolite of BPA, potential interference due to BPA contamination from containers, solvents, pipette, etc., was avoided. The standard curve had a linear regression coefficient of 0.999, and the intra‐ and inter‐assay variations were less than 10%. The assay was validated according to FDA guidelines.

Conclusions

A fast, accurate, and highly selective method for the determination of BPA‐G in human urine was developed and validated using UHPLC/MS/MS. This method is suitable for assessing human exposure to BPA. Copyright © 2016 John Wiley & Sons, Ltd.
A novel chaos‐based encryption algorithm over TCP data packet for secure communication
Authors: Çavuşoğlu Ünal , Akgül Akif , Kaçar Sezgin , Pehli̇van İhsan , Zengi̇n Ahmet
Published: January 2016

In this article, a new algorithm that can encrypt data on TCP data segment by using a novel chaotic random number generator was developed. First of all, dynamic analyses of the chaotic system to be used were made and the original pseudo‐random number generator (PRNG) with a new approach was designed. Key series produced by PRNG was tested on NIST and passed all the tests. The chaos‐based encryption here was performed on TCP, one of the most fundamental protocols in data communication. Following this, TCP data segments were encrypted by the sender on bit base with key series produced by PRNG, and then they were decrypted by the receiver. Security level of the chaos‐based encryption carried out here was tested with histogram, its key length, key sensitivity and entropy method. Memory and time usages were measured in performance analysis. So as to reveal the performance of the encryption, memory usage, encryption and decryption times were analyzed by comparison on different security algorithms. According to tests and analyses results, this chaos‐based encryption has a high level of performance and security; and it is an original study that can be used in real‐time implementations with TCP protocol. Copyright © 2016 John Wiley & Sons, Ltd.
Integrative and regularized principal component analysis of multiple sources of data
Authors: Liu Binghui , Shen Xiaotong , Pan Wei
Published: January 2016

Integration of data of disparate types has become increasingly important to enhancing the power for new discoveries by combining complementary strengths of multiple types of data. One application is to uncover tumor subtypes in human cancer research in which multiple types of genomic data are integrated, including gene expression, DNA copy number, and DNA methylation data. In spite of their successes, existing approaches based on joint latent variable models require stringent distributional assumptions and may suffer from unbalanced scales (or units) of different types of data and non‐scalability of the corresponding algorithms. In this paper, we propose an alternative based on integrative and regularized principal component analysis, which is distribution‐free, computationally efficient, and robust against unbalanced scales. The new method performs dimension reduction simultaneously on multiple types of data, seeking data‐adaptive sparsity and scaling. As a result, in addition to feature selection for each type of data, integrative clustering is achieved. Numerically, the proposed method compares favorably against its competitors in terms of accuracy (in identifying hidden clusters), computational efficiency, and robustness against unbalanced scales. In particular, compared with a popular method, the new method was competitive in identifying tumor subtypes associated with distinct patient survival patterns when applied to a combined analysis of DNA copy number, mRNA expression, and DNA methylation data in a glioblastoma multiforme study. Copyright © 2016 John Wiley & Sons, Ltd.
A Nanoplatform with Precise Control over Release of Cargo for Enhanced Cancer Therapy
Authors: Qu Qianqian , Wang Yi , Zhang Lei , Zhang Xiaobin , Zhou Shaobing
Published: January 2016

The development of a nanocarrier delivery system having both sufficient stability in blood circulation and a rapid drug release profile at target sites remains a major challenge in cancer therapy. Here, a multifunctional star‐shaped micellar system with a precisely spatiotemporal control of releasing encapsulated agents is developed by mixing a photoinitiated crosslinking amphiphilic copolymer with a phenylboronic acid (PBA)‐functionalized redox‐sensitive amphiphilic copolymer for the first time. The combination of the functional polymers effectively resolves the contradiction that the micellar system cannot release the rapid drug release in cells when it possesses an extreme stability that is often required in blood circulation. In this system, the inner core polymers are photo‐crosslinked, endowing a stable micelle matrix structure; the end groups of the hydrophilic segments are decorated with PBA ligands, providing an active targeting ability; disulfide bonds in the micellar matrix impart a redox‐responsive trigger for the prompt intracellular release of drugs. As a result, with a relatively low DOX dosage (2 mg kg−1 per injection) the in vivo antitumor effect on H22‐bearing BALB/c mice shows that the micelles have a high therapeutic efficacy against solid tumors while minimal side effects against normal tissues.
Concise Review: Paracrine Role of Stem Cells in Pituitary Tumors: A Focus on Adamantinomatous Craniopharyngioma
Authors: Martinez-Barbera Juan Pedro , Andoniadou Cynthia L.
Published: January 2016

The existence of tissue-specific progenitor/stem cells in the adult pituitary gland of the mouse has been demonstrated recently using genetic tracing experiments. These cells have the capacity to differentiate into all of the different cell lineages of the anterior pituitary and self-propagate in vitro and can therefore contribute to normal homeostasis of the gland. In addition, they play a critical role in tumor formation, specifically in the etiology of human adamantinomatous craniopharyngioma, a clinically relevant tumor that is associated with mutations in CTNNB1 (gene encoding β-catenin). Mouse studies have shown that only pituitary embryonic precursors or adult stem cells are able to generate tumors when targeted with oncogenic β-catenin, suggesting that the cell context is critical for mutant β-catenin to exert its oncogenic effect. Surprisingly, the bulk of the tumor cells are not derived from the mutant progenitor/stem cells, suggesting that tumors are induced in a paracrine manner. Therefore, the cell sustaining the mutation in β-catenin and the cell-of-origin of the tumors are different. In this review, we will discuss the in vitro and in vivo evidence demonstrating the presence of stem cells in the adult pituitary and analyze the evidence showing a potential role of these stem cells in pituitary tumors.
Performance of ultrasound‐based endometriosis staging system (UBESS) for predicting level of complexity of laparoscopic surgery for endometriosis
Authors: Menakaya U. , Reid S. , Lu C. , Bassem G. , Infante F. , Condous G.
Published: January 2016

Objective

To develop and assess the performance of a preoperative ultrasound‐based endometriosis staging system (UBESS) to predict the level of complexity of laparoscopic surgery for endometriosis.

Methods

This was a multicenter prospective and retrospective cohort study on consecutive women with suspected endometriosis who underwent laparoscopy between June 2009 and July 2013. Each woman underwent a systematic transvaginal ultrasound evaluation to assess the pelvis for different phenotypes of endometriosis, and the diagnostic performance of ultrasound for these different phenotypes was evaluated relative to the gold standard, laparoscopy. A three‐stage preoperative UBESS was developed to assess the severity of pelvic endometriosis, based on the histological phenotypes of endometriosis, the anatomical locations of deep infiltrating endometriosis and their sonographic markers of local invasiveness. The three stages of UBESS (I–III) were then correlated with the three levels of complexity of laparoscopic surgery for endometriosis described by the Royal College of Obstetricians and Gynaecologists (Levels 1–3). The end‐points were the diagnostic performance of UBESS to predict the level of complexity of laparoscopic surgery for endometriosis, i.e. UBESS stage I to predict Level‐1 laparoscopic surgery, UBESS stage II to predict Level‐2 laparoscopic surgery and UBESS stage III to predict Level‐3 laparoscopic surgery.

Results

The analysis included 192 women, with a mean ± SD age at diagnosis of endometriosis of 23.7 ± 9.3 years and a mean duration of symptoms prior to presentation of 42 months. Predominant reported locations of pelvic pain were left iliac fossa (32%), right iliac fossa (29.5%) and lower abdomen (61%) and predominant symptoms included dyspareunia (57.5%), dysmenorrhea (58.5%) and dyschezia (41.5%). The accuracy, sensitivity, specificity, positive and negative predictive values and positive and negative likelihood ratios of UBESS I for predicting a requirement for Level‐1 laparoscopic surgery were: 87.5%, 83.3%, 91.7%, 90.9%, 84.6%, 10 and 0.182; those of UBESS II for predicting Level‐2 surgery were: 87.0%, 73.7%, 90.3%, 65.1%, 93.3%, 7.6 and 0.292; and those of UBESS III for predicting Level‐3 surgery were: 95.3%, 94.8%, 95.5%, 90.2%, 97.7%, 21.2 and 0.054, respectively.

Conclusion

UBESS could be utilized to predict the level of complexity of laparoscopic surgery for endometriosis. It has the potential to facilitate the triage of women with suspected endometriosis to the most appropriate surgical expertise required for laparoscopic endometriosis surgery. UBESS needs to be validated externally in multiple centers to assess its general applicability. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.