bluuebunny/crossref_metadata_2025 huggingface dataset:
Stride-Time Variability and Fall Risk in Persons with Multiple Sclerosis
Authors: Moon Yaejin , Wajda Douglas A. , Motl Robert W. , Sosnoff Jacob J.
Published: December 2015

Gait variability is associated with falls in clinical populations. However, gait variability’s link to falls in persons with Multiple Sclerosis (PwMS) is not well established. This investigation examined the relationship between stride-time variability, fall risk, and physiological fall risk factors in PwMS. 17 PwMS (62.8±7.4years) and 17 age-matched controls (62.8±5.9years) performed the 6-minute walk test. Stride-time was assessed with accelerometers attached to the participants’ shanks. Stride-time variability was measured by interstride coefficient of variation (CV) of stride-time. The participant’s fall risk was measured by the short form physiological profile assessment (PPA). A Spearman correlation analysis was used to determine the relationship between variables. Increased fall risk was strongly associated with increased stride-time CV in both PwMS (ρ=0.71,p<0.01) and the controls (ρ=0.67,p<0.01). Fall risk was not correlated with average stride-time (p>0.05). In PwMS, stride-time CV was related to postural sway (ρ=0.74,p<0.01) while in the control group, it was related to proprioception (ρ=0.61,p<0.01) and postural sway (ρ=0.78,p<0.01). Current observations suggest that gait variability is maybe more sensitive marker of fall risk than average gait parameters in PwMS. It was also noted that postural sway may be potentially targeted to modify gait variability in PwMS.
Simultaneous Low- and High-Grade Primary Leiomyosarcomas in Two Separate Organs in a Thirty-Year Survivor of Hereditary Retinoblastoma
Authors: Moore Katherine , Tawfik Ossama , Hays Allyson , Opole Isaac
Published: December 2015

Patients with hereditary retinoblastoma have a heightened risk of developing subsequent bone and soft tissue sarcomas, exacerbated by radiation and alkylating chemotherapy. Secondary leiomyosarcomas are rare. A 29-year-old patient with bilateral retinoblastoma history presented with concurrent, independent malignancies found to be Rb-suppressed uterine and Rb-positive bladder leiomyosarcomas. She had undergone both ifosfamide chemotherapy and radiation therapy but demonstrated rare simultaneous primary leiomyosarcomas not previously described in association with ifosfamide. This rare case underlines the protean genetic predisposition to malignancy in this patient population, heightening awareness of lifelong malignancy potential, and the necessity for continuous periodic screening.
A Retrospective Evaluation of the Utility of Capsule Endoscopy and Double-Balloon Endoscopy in Crohn’s Disease
Authors: Nakamura Masanao , Hirooka Yoshiki , Watanabe Osamu , Yamamura Takeshi , Funasaka Kohei , Ohno Eizaburo , Kawashima Hiroki , Miyahara Ryoji , Goto Hidemi
Published: December 2015

Background. Although the usefulness of capsule endoscopy (CE) and double-balloon endoscopy (DBE) for the evaluation of Crohn’s disease (CD) is established, their capabilities in the differential diagnosis of small bowel stenosis have not been sufficiently addressed. The present study therefore aimed to retrospectively determine the types of patients for whom CE and DBE would confer the most benefit.Patients and Methods. We retrospectively reviewed data from 185 patients with established CD. A change of treatment based on CE or DBE results or successful DBE balloon dilation was defined as clinically useful indication. We then analyzed the factors significantly related to useful and poor indications.Results. CE results were assessed as useful indications in 28 (45%) of 62 patients. Multivariate analysis demonstrated that positive CRP and low IOIBD score are factors significantly related to a useful indication. DBE results were recognized as useful indications in 118 (77%) of 153 patients. Multivariate analysis indicated small bowel stenosis and abdominal pain as factors significantly associated with useful indications. All patients with a poor indication on CE had small bowel stenosis.Conclusions. CE was most useful for patients in clinical remission with positive CRP and without stenosis, whereas DBE was useful for patients with symptoms of stenosis.
The Potential Health Benefits of Polyphenol‐Rich Extracts from Cichorium intybus L. Studied on Caco‐2 Cells Model
Authors: Azzini Elena , Maiani Giuseppe , Garaguso Ivana , Polito Angela , Foddai Maria S. , Venneria Eugenia , Durazzo Alessandra , Intorre Federica , Palomba Lara , Rauseo Maria L. , Lombardi-Boccia Ginevra , Nobili Fabio
Published: December 2015

Phytochemicals can exert their bioactivity without reaching the systemic circulation; scarcely absorbed antioxidants might reach the large bowel contributing to protection from oxidative damage‐induced gastrointestinal diseases. In the present work, we aimed to study the relationship between potential activity of polyphenol‐rich extracts from Cichorium intybus L. and changes in morphological characteristics on Caco‐2 cells. Phytochemicals content (carotenoids and flavonoids) and total antioxidant activity of Red Chicory of Treviso and Variegated Chicory of Castelfranco were evaluated. The bioactivity of polyphenol‐rich extracts from chicories was studied in in vitro Caco‐2 cell monolayers model. Morphological characteristics changes to test the antioxidant and/or prooxidant effect were verified by histological analysis and observed by Electronic Scansion Microscopy (SEM). On Caco‐2 cell model, the polyphenols fractions from chicories have indicated a moderate antioxidant behavior until 17 μM concentration, while 70 μM and 34 μM exert cytotoxic effects for Treviso’s and Castelfranco’s Chicory, respectively, highlighted by TEER decreasing, increased permeability, and alteration of epithelium. Our findings support the beneficial effects of these products in counteracting the oxidative stress and cellular damage, induced in vitro on Caco‐2 cell model, through interaction with the mucopolysaccharide complexes in the glycocalyx, maintaining in vivo a healthy and effective intestinal barrier.
Robust Response of Streamflow Drought to Different Timescales of Meteorological Drought in Xiangjiang River Basin of China
Authors: Zhao Lin , Wu Jianjun , Fang Jian
Published: December 2015

Meteorological drought can evolve into all aspects of hydrologic system such as soil layer, groundwater, and river discharge, leading to agricultural drought, groundwater drought, and streamflow drought, respectively. How does it propagate? Is there any strong relationship between meteorological drought and others? These issues need further understanding regarding different climate regions. In this paper, monthly SRI and SPEI at different timescales during 1976 and 2005 were utilized to understand how streamflow drought responded to meteorological drought in Xiangjiang river basin, a semihumid basin of Central China. Impressive findings included that strong correlations between SRI and SPEI were found. SPEI of 2-month timescale behaved best when correlating with SRI (R=0.79). Longer timescales of SPEI seemed not to be useful for streamflow drought identification. At seasonal scale, higher correlation coefficients were obtained during dry season, whereas lower coefficients were found in wet season. The maximumRreached up to 0.89 in November at 2-month timescale. Besides, robust response relation between streamflow drought and meteorological drought was also found. The average response rate (Rr) was considerably high (75.4%), with the maximum obtained at 2-month timescale (Rr=82.9%). Meanwhile, important seasonal difference of response rate has also been pointed out.
Relationship between Evapotranspiration and Land Surface Temperature under Energy- and Water-Limited Conditions in Dry and Cold Climates
Authors: Sun Zhigang , Wang Qinxue , Batkhishig Ochirbat , Ouyang Zhu
Published: December 2015

Remotely sensed land surface temperature- (LST-) dependent evapotranspiration (ET) models and vegetation index- (VI-) LST methods may not be suitable for ET estimation in energy-limited cold areas. In this study, the relationship of ET to LST was simulated using the process-based Simultaneous Heat and Water (SHAW) model for energy- and water-limited conditions in Mongolia, to understand the differences in ET processes under these two limiting conditions in dry and cold climates. Simulation results from the SHAW model along with ground observational data showed that ET and LST have a positive relationship when air temperature (Ta) is less than or equal to the temperature (Ttra) above which plants transpire and have a negative relationship whenTais greater thanTtraunder the energy-limited condition. However, ET and LST maintain a negative relationship with changes inTaunder the water-limited condition. The differences in the relationship between ET and LST under the energy-limited and water-limited conditions could be attributed to plant transpiration and energy storage in moist/watered soil and plants. This study suggests that different strategies should be used to estimate ET under the energy-limited condition in dry and cold climates.
Emerging Roles of Filopodia and Dendritic Spines in Motoneuron Plasticity during Development and Disease
Authors: Kanjhan Refik , Noakes Peter G. , Bellingham Mark C.
Published: December 2015

Motoneurons develop extensive dendritic trees for receiving excitatory and inhibitory synaptic inputs to perform a variety of complex motor tasks. At birth, the somatodendritic domains of mouse hypoglossal and lumbar motoneurons have dense filopodia and spines. Consistent with Vaughn’s synaptotropic hypothesis, we propose a developmental unified-hybrid model implicating filopodia in motoneuron spinogenesis/synaptogenesis and dendritic growth and branching critical for circuit formation and synaptic plasticity at embryonic/prenatal/neonatal period. Filopodia density decreases and spine density initially increases until postnatal day 15 (P15) and then decreases by P30. Spine distribution shifts towards the distal dendrites, and spines become shorter (stubby), coinciding with decreases in frequency and increases in amplitude of excitatory postsynaptic currents with maturation. In transgenic mice, either overexpressing the mutated human Cu/Zn-superoxide dismutase (hSOD1G93A) gene or deficient in GABAergic/glycinergic synaptic transmission (gephyrin, GAD-67, or VGAT gene knockout), hypoglossal motoneurons develop excitatory glutamatergic synaptic hyperactivity. Functional synaptic hyperactivity is associated with increased dendritic growth, branching, and increased spine and filopodia density, involving actin-based cytoskeletal and structural remodelling. Energy-dependent ionic pumps that maintain intracellular sodium/calcium homeostasis are chronically challenged by activity and selectively overwhelmed by hyperactivity which eventually causes sustained membrane depolarization leading to excitotoxicity, activating microglia to phagocytose degenerating neurons under neuropathological conditions.
Visual Tracking Based on an Improved Online Multiple Instance Learning Algorithm
Authors: Wang Li Jia , Zhang Hua
Published: December 2015

An improved online multiple instance learning (IMIL) for a visual tracking algorithm is proposed. In the IMIL algorithm, the importance of each instance contributing to a bag probability is with respect to their probabilities. A selection strategy based on an inner product is presented to choose weak classifier from a classifier pool, which avoids computing instance probabilities and bag probabilityMtimes. Furthermore, a feedback strategy is presented to update weak classifiers. In the feedback update strategy, different weights are assigned to the tracking result and template according to the maximum classifier score. Finally, the presented algorithm is compared with other state-of-the-art algorithms. The experimental results demonstrate that the proposed tracking algorithm runs in real-time and is robust to occlusion and appearance changes.
Abnormal Resting-State Functional Connectivity Strength in Mild Cognitive Impairment and Its Conversion to Alzheimer’s Disease
Authors: Li Yuxia , Wang Xiaoni , Li Yongqiu , Sun Yu , Sheng Can , Li Hongyan , Li Xuanyu , Yu Yang , Chen Guanqun , Hu Xiaochen , Jing Bin , Wang Defeng , Li Kuncheng , Jessen Frank , Xia Mingrui , Han Ying
Published: December 2015

Individuals diagnosed with mild cognitive impairment (MCI) are at high risk of transition to Alzheimer’s disease (AD). However, little is known about functional characteristics of the conversion from MCI to AD. Resting-state functional magnetic resonance imaging was performed in 25 AD patients, 31 MCI patients, and 42 well-matched normal controls at baseline. Twenty-one of the 31 MCI patients converted to AD at approximately 24 months of follow-up. Functional connectivity strength (FCS) and seed-based functional connectivity analyses were used to assess the functional differences among the groups. Compared to controls, subjects with MCI and AD showed decreased FCS in the default-mode network and the occipital cortex. Importantly, the FCS of the left angular gyrus and middle occipital gyrus was significantly lower in MCI-converters as compared with MCI-nonconverters. Significantly decreased functional connectivity was found in MCI-converters compared to nonconverters between the left angular gyrus and bilateral inferior parietal lobules, dorsolateral prefrontal and lateral temporal cortices, and the left middle occipital gyrus and right middle occipital gyri. We demonstrated gradual but progressive functional changes during a median 2-year interval in patients converting from MCI to AD, which might serve as early indicators for the dysfunction and progression in the early stage of AD.
Validation of Housekeeping Genes to Study Human Gingival Stem Cells and Their In Vitro Osteogenic Differentiation Using Real‐Time RT‐qPCR
Authors: Taïhi Ihsène , Nassif Ali , Berbar Tsouria , Isaac Juliane , Berdal Ariane , Gogly Bruno , Fournier Benjamin Philippe
Published: December 2015

Gingival stem cells (GSCs) are recently isolated multipotent cells. Their osteogenic capacity has been validated in vitro and may be transferred to human cell therapy for maxillary large bone defects, as they share a neural crest cell origin with jaw bone cells. RT‐qPCR is a widely used technique to study gene expression and may help us to follow osteoblast differentiation of GSCs. For accurate results, the choice of reliable housekeeping genes (HKGs) is crucial. The aim of this study was to select the most reliable HKGs for GSCs study and their osteogenic differentiation (dGSCs). The analysis was performed with ten selected HKGs using four algorithms: ΔCt comparative method, GeNorm, BestKeeper, and NormFinder. This study demonstrated that three HKGs, SDHA, ACTB, and B2M, were the most stable to study GSC, whereas TBP, SDHA, and ALAS1 were the most reliable to study dGSCs. The comparison to stem cells of mesenchymal origin (ASCs) showed that SDHA/HPRT1 were the most appropriate for ASCs study. The choice of suitable HKGs for GSCs is important as it gave access to an accurate analysis of osteogenic differentiation. It will allow further study of this interesting stem cells source for future human therapy.
Mechanical Properties of a “5+4” Viscoelastic Damping Wall Based on Full-Scale Laboratory Tests
Authors: Xu Junhong , Li Aiqun
Published: December 2015

This paper presented temperature scanning tests of the viscoelastic materials firstly. The temperature scanning tests were carried out by a Rheogel-E4000DMA analyzer and the results showed the modulus and loss factor of viscoelastic damping material. Secondly, the full-scale laboratory test of the “5+4” VDW was carried out. The test was conducted on an electrohydraulic servo tester. A new shear loading mode in the transverse direction was proposed for the VDW. And the maximum damping force, the storage stiffness, the loss stiffness, equivalent damping coefficient, the shear storage modulus, the shear loss modulus, and the loss factor were discussed in the text.
Cell Line‐Dependent Variability of Coordinate Expression of p75NTR and CRABP1 and Modulation of Effects of Fenretinide on Neuroblastoma Cells
Authors: Yang Yaoli Pu , Wang Simeng , Li Xingguo , Schor Nina F.
Published: December 2015

Neuroblastoma is a childhood neural crest tumor. Fenretinide, a retinoic acid analogue, induces accumulation of mitochondrial reactive oxygen species and consequent apoptosis in neuroblastoma cells. The p75 neurotrophin receptor (p75NTR) enhances the antineuroblastoma cell efficacy of fenretinide in vitro. We examined the role of the retinoid binding protein, CRABP1, in p75NTR‐mediated potentiation of the efficacy of fenretinide. Knockdown and overexpression, respectively, of either p75NTR or CRABP1 were effected in neuroblastoma cell lines using standard techniques. Expression was determined by qRT‐PCR and confirmed at the protein level by Western blot. Metabolic viability was determined by Alamar blue assay. While protein content of CRABP1 correlated roughly with that of p75NTR in the three neuroblastoid or epithelioid human neuroblastoma cell lines studied, manipulation of p75NTR expression resulted in cell line‐dependent, variable change in CRABP1 expression. Furthermore, in some cell lines, induced expression of CRABP1 in the absence of p75NTR did not alter cell sensitivity to fenretinide treatment. The effects of manipulation of p75NTR expression on CRABP1 expression and the effects of CRABP1 expression on fenretinide efficacy are therefore neuroblastoma cell line‐dependent. Potentiation of the antineuroblastoma cell effects of fenretinide by p75NTR is not mediated solely through CRABP1.
Upper Limb Immobilisation: A Neural Plasticity Model with Relevance to Poststroke Motor Rehabilitation
Authors: Furlan Leonardo , Conforto Adriana Bastos , Cohen Leonardo G. , Sterr Annette
Published: December 2015

Advances in our understanding of the neural plasticity that occurs after hemiparetic stroke have contributed to the formulation of theories of poststroke motor recovery. These theories, in turn, have underpinned contemporary motor rehabilitation strategies for treating motor deficits after stroke, such as upper limb hemiparesis. However, a relative drawback has been that, in general, these strategies are most compatible with the recovery profiles of relatively high-functioning stroke survivors and therefore do not easily translate into benefit to those individuals sustaining low-functioning upper limb hemiparesis, who otherwise have poorer residual function. For these individuals, alternative motor rehabilitation strategies are currently needed. In this paper, we will review upper limb immobilisation studies that have been conducted with healthy adult humans and animals. Then, we will discuss how the findings from these studies could inspire the creation of a neural plasticity model that is likely to be of particular relevance to the context of motor rehabilitation after stroke. For instance, as will be elaborated, such model could contribute to the development of alternative motor rehabilitation strategies for treating poststroke upper limb hemiparesis. The implications of the findings from those immobilisation studies for contemporary motor rehabilitation strategies will also be discussed and perspectives for future research in this arena will be provided as well.
Nutritional Omega-3 Deficiency Alters Glucocorticoid Receptor-Signaling Pathway and Neuronal Morphology in Regionally Distinct Brain Structures Associated with Emotional Deficits
Authors: Larrieu Thomas , Hilal Muna L. , De Smedt-Peyrusse Véronique , Sans Nathalie , Layé Sophie
Published: December 2015

Extensive evidence suggests that long term dietary n-3 polyunsaturated fatty acids (PUFAs) deficiency results in altered emotional behaviour. We have recently demonstrated that n-3 PUFAs deficiency induces emotional alterations through abnormal corticosterone secretion which leads to altered dendritic arborisation in the prefrontal cortex (PFC). Here we show that hypothalamic-pituitary-adrenal (HPA) axis feedback inhibition was not compromised in n-3 deficient mice. Rather, glucocorticoid receptor (GR) signaling pathway was inactivated in the PFC but not in the hippocampus of n-3 deficient mice. Consequently, only dendritic arborisation in PFC was affected by dietary n-3 PUFAs deficiency. In addition, occlusion experiment with GR blockade altered GR signaling in the PFC of control mice, with no further alterations in n-3 deficient mice. In conclusion, n-3 PUFAs deficiency compromised PFC, leading to dendritic atrophy, but did not change hippocampal GR function and dendritic arborisation. We argue that this GR sensitivity contributes to n-3 PUFAs deficiency-related emotional behaviour deficits.
Numerical Simulation of the Topographical Change in Korea Mountain Area by Intense Rainfall and Consequential Debris Flow
Authors: Jun Byong-Hee
Published: December 2015

The objectives of this study are to simulate the topographical changes associated with rainfall and the consequential debris flow using terrestrial LiDAR (Light Detection And Ranging). Three rainfall events between July 9 and July 14, 2009, triggered a number of debris flows at Jecheon County in Korea. Rain fell at a rate of 64 mm/h, producing 400 mm of total accumulation during this period. Tank simulation model for SWI (Soil Water Index) estimated the water stored beneath the ground and debris flow occurrence in study area. For the LiDAR (Light Detection and Ranging) survey, the terrestrial laser scanning system RIEGL LMS-Z390i consists of an accurate and fast 3D scanner, associated RTK GPS system. The DEM derived from LiDAR enabled the debris flow to be mapped and analyzed in great detail. The estimated affected area and erosion/deposition volumes by debris flow were compared with two-dimensional numerical simulation. The simulation results were sufficiently in good agreement with the debris flow track, and a success rate of over 90% was achieved with a simulation time of 300 s. A comparison of the simulated and surveyed results based on deposition volume yields a success rate of over 97% with 350 s of simulation time.
Novel Hyperbolic Homoclinic Solutions of the Helmholtz-Duffing Oscillators
Authors: Chen Yang-Yang , Chen Shu-Hui , Wang Wei-Wei
Published: December 2015

The exact and explicit homoclinic solution of the undamped Helmholtz-Duffing oscillator is derived by a presented hyperbolic function balance procedure. The homoclinic solution of the self-excited Helmholtz-Duffing oscillator can also be obtained by an extended hyperbolic perturbation method. The application of the present homoclinic solutions to the chaos prediction of the nonautonomous Helmholtz-Duffing oscillator is performed. Effectiveness and advantage of the present solutions are shown by comparisons.
Inflammation in Benign Prostate Tissue and Prostate Cancer in the Finasteride Arm of the Prostate Cancer Prevention Trial
Authors: Murtola Teemu J. , Gurel Bora , Umbehr Martin , Lucia M. Scott , Thompson Ian M. , Goodman Phyllis J. , Kristal Alan R. , Parnes Howard L. , Lippman Scott M. , Sutcliffe Siobhan , Peskoe Sarah B. , Barber John R. , Drake Charles G. , Nelson William G. , De Marzo Angelo M. , Platz Elizabeth A.
Published: December 2015

Background: A previous analysis of the placebo arm of the Prostate Cancer Prevention Trial (PCPT) reported 82% overall prevalence of intraprostatic inflammation and identified a link between inflammation and higher-grade prostate cancer and serum PSA. Here, we studied these associations in the PCPT finasteride arm.

Methods: Prostate cancer cases (N = 197) detected either on a clinically indicated biopsy or on protocol-directed end-of-study biopsy, and frequency-matched controls (N = 248) with no cancer on an end-of-study biopsy were sampled from the finasteride arm. Inflammation in benign prostate tissue was visually assessed using digital images of hematoxylin and eosin–stained sections. Logistic regression was used for statistical analysis.

Results: In the finasteride arm, 91.6% of prostate cancer cases and 92.4% of controls had at least one biopsy core with inflammation in benign areas (P < 0.001 for difference compared with placebo arm). Overall, the odds of prostate cancer did not differ by prevalence [OR, 0.90; 95% confidence interval (CI), 0.44–1.84] or extent (P trend = 0.68) of inflammation. Inflammation was not associated with higher-grade disease (prevalence: OR, 1.07; 95% CI, 0.43–2.69). Furthermore, mean PSA concentration did not differ by the prevalence or extent of inflammation in either cases or controls.

Conclusion: The prevalence of intraprostatic inflammation was higher in the finasteride than placebo arm of the PCPT, with no association with higher-grade prostate cancer.

Impact: Finasteride may attenuate the association between inflammation and higher-grade prostate cancer. Moreover, the missing link between intraprostatic inflammation and PSA suggests that finasteride may reduce inflammation-associated PSA elevation. Cancer Epidemiol Biomarkers Prev; 25(3); 463–9. ©2015 AACR.
Hif1a Deletion Reveals Pro-Neoplastic Function of B Cells in Pancreatic Neoplasia
Authors: Lee Kyoung Eun , Spata Michelle , Bayne Lauren J. , Buza Elizabeth L. , Durham Amy C. , Allman David , Vonderheide Robert H. , Simon M. Celeste
Published: December 2015

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related deaths worldwide, with an exceedingly low 5-year survival rate. PDAC tumors are characterized by an extensive desmoplastic stromal response and hypovascularity, suggesting that tumor hypoxia could regulate PDAC initiation and/or progression. Using a well-defined, autochthonous KrasG12D-driven murine model, as well as human tumors, we demonstrate that hypoxia and stabilization of hypoxia-inducible factor 1α (HIF1α), a principal mediator of hypoxic adaptation, emerge early during preinvasive stages of PDAC. Surprisingly, pancreas-specific Hif1a deletion drastically accelerated KrasG12D-driven pancreatic neoplasia and was accompanied by significant increases in intrapancreatic B lymphocytes, featuring prominent influx of a rare “B1b” B-cell subtype. Finally, treatment of HIF1α-deficient mice with B cell–depleting αCD20 monoclonal antibodies inhibited progression of pancreatic intraepithelial neoplasia (PanIN). Our data reveal a previously unrecognized role for B cells in promoting pancreatic tumorigenesis and implicate HIF1α as a critical regulator of PDAC development.

Significance: We show here that pancreas-specific Hif1a deletion promotes PDAC initiation, coincident with increased intrapancreatic accumulation of B cells, and that B-cell depletion suppresses pancreatic tumorigenesis. We therefore demonstrate a protective role for HIF1α in pancreatic cancer initiation and uncover a previously unrecognized function of B cells. Cancer Discov; 6(3); 256–69. ©2015 AACR.

See related commentary by Roghanian et al., p. 230.

See related article by Pylayeva-Gupta et al., p. 247.

See related article by Gunderson et al., p. 270.

This article is highlighted in the In This Issue feature, p. 217
Bruton Tyrosine Kinase–Dependent Immune Cell Cross-talk Drives Pancreas Cancer
Authors: Gunderson Andrew J. , Kaneda Megan M. , Tsujikawa Takahiro , Nguyen Abraham V. , Affara Nesrine I. , Ruffell Brian , Gorjestani Sara , Liudahl Shannon M. , Truitt Morgan , Olson Peter , Kim Grace , Hanahan Douglas , Tempero Margaret A. , Sheppard Brett , Irving Bryan , Chang Betty Y. , Varner Judith A. , Coussens Lisa M.
Published: December 2015

Pancreas ductal adenocarcinoma (PDAC) has one of the worst 5-year survival rates of all solid tumors, and thus new treatment strategies are urgently needed. Here, we report that targeting Bruton tyrosine kinase (BTK), a key B-cell and macrophage kinase, restores T cell–dependent antitumor immune responses, thereby inhibiting PDAC growth and improving responsiveness to standard-of-care chemotherapy. We report that PDAC tumor growth depends on cross-talk between B cells and FcRγ+ tumor–associated macrophages, resulting in TH2-type macrophage programming via BTK activation in a PI3Kγ-dependent manner. Treatment of PDAC-bearing mice with the BTK inhibitor PCI32765 (ibrutinib) or by PI3Kγ inhibition reprogrammed macrophages toward a TH1 phenotype that fostered CD8+ T-cell cytotoxicity, and suppressed PDAC growth, indicating that BTK signaling mediates PDAC immunosuppression. These data indicate that pharmacologic inhibition of BTK in PDAC can reactivate adaptive immune responses, presenting a new therapeutic modality for this devastating tumor type.

Significance: We report that BTK regulates B-cell and macrophage-mediated T-cell suppression in pancreas adenocarcinomas. Inhibition of BTK with the FDA-approved inhibitor ibrutinib restores T cell–dependent antitumor immune responses to inhibit PDAC growth and improves responsiveness to chemotherapy, presenting a new therapeutic modality for pancreas cancer. Cancer Discov; 6(3); 270–85. ©2015 AACR.

See related commentary by Roghanian et al., p. 230.

See related article by Pylayeva-Gupta et al., p. 247.

See related article by Lee et al., p. 256.

This article is highlighted in the In This Issue feature, p. 217
Application of Sequencing, Liquid Biopsies, and Patient-Derived Xenografts for Personalized Medicine in Melanoma
Authors: Girotti Maria Romina , Gremel Gabriela , Lee Rebecca , Galvani Elena , Rothwell Dominic , Viros Amaya , Mandal Amit Kumar , Lim Kok Haw Jonathan , Saturno Grazia , Furney Simon J. , Baenke Franziska , Pedersen Malin , Rogan Jane , Swan Jacqueline , Smith Matthew , Fusi Alberto , Oudit Deemesh , Dhomen Nathalie , Brady Ged , Lorigan Paul , Dive Caroline , Marais Richard
Published: December 2015

Targeted therapies and immunotherapies have transformed melanoma care, extending median survival from ∼9 to over 25 months, but nevertheless most patients still die of their disease. The aim of precision medicine is to tailor care for individual patients and improve outcomes. To this end, we developed protocols to facilitate individualized treatment decisions for patients with advanced melanoma, analyzing 364 samples from 214 patients. Whole exome sequencing (WES) and targeted sequencing of circulating tumor DNA (ctDNA) allowed us to monitor responses to therapy and to identify and then follow mechanisms of resistance. WES of tumors revealed potential hypothesis-driven therapeutic strategies for BRAF wild-type and inhibitor-resistant BRAF-mutant tumors, which were then validated in patient-derived xenografts (PDX). We also developed circulating tumor cell–derived xenografts (CDX) as an alternative to PDXs when tumors were inaccessible or difficult to biopsy. Thus, we describe a powerful technology platform for precision medicine in patients with melanoma.

Significance: Although recent developments have revolutionized melanoma care, most patients still die of their disease. To improve melanoma outcomes further, we developed a powerful precision medicine platform to monitor patient responses and to identify and validate hypothesis-driven therapies for patients who do not respond, or who develop resistance to current treatments. Cancer Discov; 6(3); 286–99. ©2015 AACR.

This article is highlighted in the In This Issue feature, p. 217
A Call to Reduce the Use of Bridging Anticoagulation
Authors: Rose Adam J. , Allen Arthur L. , Minichello Tracy
Published: December 2015

Because of the recent publication of several important studies, there has been a major change in how we think about perioperative management of anticoagulation. Because of these changes, existing consensus guidelines are suddenly out of date and can no longer be used as is, particularly the 2012 American College of Chest Physicians Antithrombotic Guidelines, version 9. We estimate that well over 90% of patients receiving warfarin therapy should not receive bridging anticoagulation during periprocedural interruptions of therapy, except under unusual circumstances and with appropriate justification. Accumulating evidence also suggests that bridging is not indicated among patients receiving direct-acting oral anticoagulant therapy. The large number of patients potentially affected represents an important safety concern and requires an immediate change in practice.
Responses to nitrate pollution, warming and density in common frog tadpoles (Rana temporaria)
Authors: Egea-Serrano Andrés , Van Buskirk Josh
Published: December 2015

Amphibians face a variety of anthropogenic environmental perturbations that could act alone or in combination to influence population size. We investigated interactive effects of warming conditions, a moderate pulse of nitrogen pollution, and conspecific density on larvae of the common frog,Rana temporaria. The 16-day experiment had a 2 × 2 × 2 factorial design implemented in 80-l outdoor mesocosms. High density and warm temperature both resulted in reduced activity and visibility; tadpoles grew and developed more quickly at low density and high temperature. The high-nitrogen treatment did not influence behavior, growth, or development rate. We attribute this to several realistic features of our study, including a pulsed treatment application and natural denitrification within the mesocosms. There was only a single interaction among the three factors: higher temperature exacerbated density-dependence in growth rate. These results illustrate that climate warming may benefit temperate amphibians, although the benefits may be counteracted by enhanced larval crowding.
The Effects of Varying Break Length on Attention and Time on Task
Authors: Lim Julian , Kwok Kenneth
Published: December 2015

Objective:

We aimed to discover how varying the length of task breaks would affect the time-on-task effect in subsequent testing periods.

Background:

An important means of preventing errors and accidents caused by mental fatigue and time on task is to intersperse rest intervals within long work periods. Most studies of rest pauses to date have examined their effects in real-world tasks and settings, and their subtler effects on behavior, as measurable by laboratory paradigms, are not well understood.

Method:

We studied a group of 71 participants as they completed a 1-hr auditory oddball task with two rest opportunities. Rest intervals were 1, 5, or 10 min long.

Results:

Improvements in reaction time were significantly positively associated with length of the rest break. However, longer breaks were also associated with steeper decrements in performance in the subsequent task block. Across individuals, the amount of immediate improvement correlated with the extent of later decline.

Conclusion:

Our results support a resource/effort-allocation model of fatigue, whereby longer breaks bias participants toward greater effort expenditure on resumption of the task when cognitive resources may not have been fully replenished.

Application:

These findings may have implications for the refinement of work-rest schedules in industries where time-on-task degradation in performance is an important concern.
Haptic Communication in Collaborative Virtual Environments
Authors: Wang Jinling , Chellali Amine , Cao Caroline G. L.
Published: December 2015

Objective:

To understand the interaction between haptic and verbal communication, we quantified the relative effect of verbal, haptic, and haptic-plus-verbal feedback in a collaborative virtual pointing task.

Background:

Collaborative virtual environments (CVEs) provide a medium for interaction among remote participants. Better understanding of the role of haptic feedback as a supplement to verbalization can improve the design of CVEs.

Methods:

Thirty-six participants were randomly paired into 18 dyads to complete a 2-D pointing task in a CVE. In a mixed experimental design, participants completed the task in three communication conditions: haptic only (H), verbal only (V), and haptic plus verbal (HV). The order of the conditions presented to the participants was counterbalanced.

Results:

The time to task completion, path length, overshoot, and root mean square error were analyzed. Overall, performance in the V and HV conditions was significantly better than in the H condition. H was the least efficient communication channel but elicited response with the shortest reaction time. When verbalization was not available, the use of the haptic device was more likely to be exaggerated to ensure information transmission. When verbalization was used, participants converged on the use of a Cartesian coordinate system for communicating spatial information.

Conclusion:

Haptic communication can be used to complete a collaborative virtual task but is less efficient than verbal communication. A training period may help to improve the efficiency of haptic communication.

Application:

These results can be used to design remote collaboration tasks incorporating haptic components and for improving the design of CVEs that support haptic communication.
SPIDER
Authors: Strayer David L. , Fisher Donald L.
Published: December 2015

Objective:

The objective was to identify key cognitive processes that are impaired when drivers divert attention from driving.

Background:

Driver distraction is increasingly recognized as a significant source of injuries and fatalities on the roadway.

Method/Results:

A “SPIDER” model is developed that identifies key cognitive processes that are impaired when drivers divert attention from driving. SPIDER is an acronym standing for scanning, predicting, identifying, decision making, and executing a response.

Conclusion:

When drivers engage in secondary activities unrelated to the task of driving, SPIDER-related processes are impaired, situation awareness is degraded, and the ability to safely operate a motor vehicle may be compromised.

Application:

The pattern of interference helps to illuminate the sources of driver distraction and may help guide the integration of new technology into the automobile.
Measuring and Controlling the Exhaust Emission from DI Diesel Engine Using Biofuel as an Environment Fuel
Authors: Kanthavelkumaran Natesan , Seenikannan P , Kumaresh E
Published: December 2015

Today, world’s energy needs are met all the way through fossil fuels and natural gas. As an outcome, the amount of fossil fuel is diminishing from year to year. This article shows the prospect of coconut oil as a renewable and alternative fuel for diesel. The diesel engine has versatile uses in small power generation and automobile sectors. This article is mainly focused on the performance and emission strategy while using biofuel as a substitute in diesel engine. An experimental arrangement is used to study the performance of a small diesel engine using different blends of biodiesel converted from coconut oil. With biodiesel, the engine is proficient running without difficulty. Different blends of biodiesel (i.e. B75, B50, and B25) have been used to avoid problematical modification of the engine or the fuel supply system. In conclusion, a comparison of engine performance for different blends of biodiesel has been accepted to determine the best possible blend for different operating conditions. As per the case study, coconut oil–diesel fuel blend resulted in lower smoke and NOx emissions. Besides, this research mainly focuses that the concentrations of biofuel increase the emissions of carbonyl compounds and that of acetaldehyde when compared with results from sole fuel (diesel) with same engine. Possible impacts of changing diesel to B75 diesel indicate an increase of ozone formation. In terms of environment health, a lower impact was projected considering only the changes in biofuel concentrations.
Addressing the physical health of people with serious mental illness: A potential solution for an enduring problem
Authors: Happell Brenda , Gaskin Cadeyrn J , Stanton Robert
Published: December 2015

People with serious mental illness face significant inequalities in physical health care. As a result, the risk of cardiometabolic disorders and premature mortality is far greater than that observed in the general population. Contributiung to this disparity, is the lack of routine physical health screening by mental health clinicians. One possible solution is the implimentation of a physical health nurse consultant, whose role is to monitor and coordinate the physical health care of people with serious mental illness. Current evidence supports the implimentation of such a role, and a failure to address the widening gaps in physical health care will only serve to increase the disparities faced by people with serious mental illness.
What can increase the default risk in local governments?
Authors: Navarro-Galera Andrés , Lara-Rubio Juan , Buendía-Carrillo Dionisio , Rayo-Cantón Salvador
Published: December 2015

Concern has been expressed by international organisations and in previous studies about the financial situation of local governments, and the question of debt has been identified as a crucial element in efforts to overcome the current financial crisis. However, the variables that can affect the financial soundness of these governments have not been sufficiently studied, despite their direct relation to the credit risk premium. In this article, we aim to identify risk factors for default by local governments, and provide useful information to municipal financial managers. We conducted an empirical study of 148 Spanish municipalities and analysed data from four years, applying a random effects logistic regression model. Our findings reveal that a lower population density, less dependent population, falling levels of per capita income and the presence of progressive local government are all risk factors for default by local governments. Furthermore, our findings indicate that the general financing structure variable and debt composition and maturity variable do influence the risk of default by local governments.

Points for practitioners

The findings of this article can provide useful information for managers and politicians responsible for the financial management of local governments, in particular, by enabling them to better understand the risk premiums assigned by banks. Specifically, by identifying the risk factors for default, this article highlights the warning signs of this risk, so that suitable arguments may be expressed in negotiating loan repayment schedules and interest rates, and in designing financial viability and restructuring plans.
Intercultural policy and multi-level governance in Barcelona: mainstreaming comprehensive approach
Authors: Zapata-Barrero Ricard
Published: December 2015

The main purpose of this article is to analyse Barcelona’s mainstreaming approach to intercultural policy from the beginning of its immigration process. My key questions are threefold: (a) why was Barcelona attracted by the intercultural approach so early in 1997? (b) how can we understand the consolidation of interculturalism? and (c) how can its successful permanent endurance (16 years) be explained, given different migratory contexts/political governments? I will argue that Barcelona’s status as a key player within the multi-level system of Catalan and Spanish governance has been a favourable key factor.

I will first feature the mainstreaming approach, and then defend the argument that the vertical dimension has helped to strengthen the legitimacy of the horizontal dimension, as it has provided a favourable environment in which interculturalism can flourish. I conclude by highlighting the fact that the analysis of Barcelona helps to provide new meanings for the multi-level governance debate in diverse European cities.

Points for practitioners

Multi-level governance and cities networks influence the policy design and the consolidation of cities’ diversity policies. There is an assumed link for cities between intercultural policies and the mainstreaming approach in diversity policies. The relationship between the vertical and horizontal dimensions of multi-level governance plays a key role in promoting a favourable environment for these policies to thrive.
National culture and public service motivation: investigating the relationship using Hofstede’s five cultural dimensions
Authors: Kim Sangmook
Published: December 2015

Much research has focused on finding and explaining the antecedents, correlates, and outcomes of public service motivation (PSM), but little is known about the influence of national context on individuals’ PSM. Previous research suggests that national culture may exert an independent influence on individuals’ PSM. This article examines PSM as an individual-level variable that is related to national culture, which is represented by Hofstede’s cultural dimensions. Using data from the International Social Survey Programme (2005), I investigate the relationship between cultural dimensions and individuals’ PSM. This article demonstrates that masculinity and indulgence are positively related to individuals’ PSM, whereas individualism is negatively associated with individuals’ PSM. However, power distance and uncertainty avoidance have a non-significant relationship with PSM. This article provides partial support for the thesis that national culture is associated with individuals’ PSM, but future research is required to explicate the relationship of cultural characteristics to individuals’ PSM.

Points for practitioners

Culture influences certain types of behavior both directly and indirectly. The article suggests that cultural tendencies such as masculinity, indulgence, and collectivism have a significant positive influence on individuals’ PSM. Organizational education and socialization enhancing these cultural values are likely to foster employees’ PSM.
Comparing local politicians’ and bureaucrats’ assessments of democratic participation: the cases of Norway and Sweden
Authors: Pierre Jon , Røiseland Asbjørn , Peters B. Guy , Gustavsen Annelin
Published: December 2015

Given the increasing emphasis on delivery and output as a source of legitimacy for local government, how do politicians and civil servants perceive conventional, input-based channels for citizens’ influence on government in relationship to performance and output-oriented opportunities to influence public service? This article compares the attitudes of senior local politicians and civil servants in Norwegian and Swedish local authorities on these issues. The analysis draws on a data set collected among political and administrative leaders in Norwegian and Swedish local authorities. We also compare a service sector where public management reform has been extensive (care of the elderly) with a service sector where regulation and law enforcement dominates (planning and construction). The analysis suggests that there is a significant similarity between politicians’ and bureaucrats’ attitudes, although politicians accord greater importance to input-based channels of influence and to throughput than do bureaucrats.

Points for practitioners

Public management reform provides a new channel for clients to influence public service directly through the providers of those services and not through conventional political channels. This article studies how politicians and public servants in Norwegian and Swedish municipalities evaluate conventional and new channels for clients to influence service delivery. We also compare service sectors where such choice is extensive with areas where choice is much more constrained. Overall, we find that politicians tend to favor conventional political channels for clients’ influence whereas public servants take a more positive view of clients approaching the executive side of the local authority.