bluuebunny/crossref_metadata_2025 huggingface dataset:
Including ecotoxic impacts on warm-blooded predators in life cycle impact assessment
Authors: Golsteijn Laura , van Zelm Rosalie , Veltman Karin , Musters Gijs , Hendriks A Jan , Huijbregts Mark AJ
Published: July 2011

In current life cycle impact assessment, the focus of ecotoxicity is on cold-blooded species. We developed a method to calculate characterization factors (CFs) for the impact assessment of chemical emissions on warm-blooded predators in freshwater food chains. The method was applied to 329 organic chemicals. The CF for these predators was defined as a multiplication of the fate factor (FF), exposure factor (XF), bioaccumulation factor (BF), and effect factor (EF). Fate factors and XFs were calculated with the model USES-LCA 2.0. Bioaccumulation factors were calculated with the model OMEGA, for chemical uptake via freshwater, food, and air. Effect factors were calculated based on experimental, median lethal doses (LD50). The concentration buildup (CB) of the chemicals (i.e., FF, XF, and BF over the 3 routes of exposure) showed a range of 7 to 9 orders of magnitude, depending on the emission compartment. Effect factors displayed a range of 7 orders of magnitude. Characterization factors ranged 9 orders of magnitude. After emissions to freshwater, the relative contribution of the uptake routes to CB were 1% (90% confidence interval [CI]: 0%–2%) for uptake from air, 43% (11%–50%) for uptake from water, and 56% (50%–87%) for uptake from food. After an emission to agricultural soil, the contribution was 11% (0%–80%) for uptake from air, 39% (5%–50%) for uptake from water, and 50% (11%–83%) for uptake from food. Uptake from air was mainly relevant for emissions to air (on average 42%, 90% CI: 5%–98%). Characterization factors for cold-blooded species were typically 4 orders of magnitude higher than CFs for warm-blooded predators. The correlation between both types of CFs was low, which means that a high relative impact on cold-blooded species does not necessarily indicate a high relative impact on warm-blooded predators. Depending on the weighing method to be considered, the inclusion of impacts on warm-blooded predators can change the relative ranking of toxic chemicals in a life cycle assessment. Integr Environ Assess Manag 2012; 8: 372–378. © 2011 SETAC
Dickkopf‐3 is regulated by the MYCN‐induced miR‐17‐92 cluster in neuroblastoma
Authors: De Brouwer Sara , Mestdagh Pieter , Lambertz Irina , Pattyn Filip , De Paepe Anne , Westermann Frank , Schroeder Christina , Schulte Johannes H. , Schramm Alexander , De Preter Katleen , Vandesompele Jo , Speleman Frank
Published: July 2011

Neuroblastoma (NB) is a paediatric tumour with a remarkable diverse clinical behaviour. Approximately half of the high stage aggressive tumours are characterized by MYCN gene amplification but our understanding of the role of MYCN in NB oncogenesis is incomplete. Previous studies have shown that MYCN expression is inversely correlated with expression of Dickkopf‐3 (DKK3), a gene encoding an extracellular protein with presumed tumour suppressor activity, but direct MYCN regulation of DKK3 was excluded leaving the mechanism of regulation unexplained. Given the recently established role of MYCN‐regulated miRNAs in downregulation of protein‐coding genes and predicted seeds for miR‐17‐92 cluster members within the DKK3 3′UTR, we hypothesized that this mechanism would act in MYCN regulation of DKK3. To investigate this, we used a validated miR‐17‐92‐inducible cellular system and could demonstrate robust downregulation of DKK3 mRNA and protein levels upon miR‐17‐92 overexpression. Next, two of the three predicted miRNAs, miR‐19b and miR‐92a, were shown to lower DKK3 protein levels, in addition to measurable DKK3 mRNA knock‐down by miR‐92a. Direct interaction between miR‐19b or miR‐92a and the 3′UTR of DKK3 was validated using luciferase reporter assays. In conclusion, this study demonstrates that the MYCN‐induced downregulation of DKK3 results from direct upregulation of miR‐17‐92 components effecting both DKK3 mRNA stability and translation which further contributes to the pleiotropic oncogenic effect of elevated MYCN levels. The strict MYCN‐mediated regulation of DKK3 is suggestive for an important downstream function of the MYCN protein and thus warrants further investigations to unravel the role of DKK3 in NB.
L1‐CAM‐targeted antibody therapy and 177Lu‐radioimmunotherapy of disseminated ovarian cancer
Authors: Fischer Eliane , Grünberg Jürgen , Cohrs Susan , Hohn Alexander , Waldner‐Knogler Karin , Jeger Simone , Zimmermann Kurt , Novak‐Hofer Ilse , Schibli Roger
Published: July 2011

The L1‐cell adhesion molecule (L1‐CAM) is highly expressed in various cancer types including ovarian carcinoma but is absent from most normal tissue. A chimeric monoclonal antibody, chCE7, specifically binds to human L1‐CAM and exhibits anti‐proliferative effects on L1‐CAM‐expressing tumor cells. The goal of this study was to evaluate the efficacy of a novel 177Lu‐chCE7 radioimmunotherapeutic agent and to compare it to a treatment protocol with unlabeled, growth‐inhibiting chCE7 in a mouse xenograft model of disseminated ovarian cancer. chCE7agl, an aglycosylated IgG1 variant with improved pharmacokinetics, was conjugated with 1,4,7,10‐tetraazacyclododecane‐N‐N′‐N′‐N‴‐tetraacetic acid (DOTA) and labeled with the low‐energy β‐emitter 177Lu. Tumor growth and survival were assessed after a single i.v. dose of 8 MBq (60 μg) radioimmunoconjugate in nude mice bearing either subcutaneous or intraperitoneal SKOV3.ip1 human ovarian cancer tumors. Therapeutic efficacy was compared with three times weekly i.p. administration of 10 mg/kg unconjugated chCE7. In vivo analysis of 177Lu‐chCE7agl biodistribution demonstrated high and specific accumulation of radioactivity at the tumor site with maximal tumor uptake of up to 48.0 ± 8.1% ID/g at 168 h postinjection. A single treatment with 177Lu‐DOTA‐chCE7agl caused significant retardation of tumor growth and prolonged median survival from 33 to 71 days, while administration of a nontargeted 177Lu‐immunoconjugate had no beneficial effect. Three times weekly i.p. application of unlabeled chCE7 10 mg/kg similarly increased survival from 44 to 72 days. We conclude that a single dose of 177Lu‐DOTA‐chCE7agl is as effective as repeated administration of nonradioactive chCE7 for treatment of small intraperitoneal tumors expressing L1‐CAM.
Inhibition of sonic hedgehog pathway and pluripotency maintaining factors regulate human pancreatic cancer stem cell characteristics
Authors: Tang Su‐Ni , Fu Junsheng , Nall Dara , Rodova Mariana , Shankar Sharmila , Srivastava Rakesh K.
Published: July 2011

Activation of the sonic hedgehog (SHh) pathway is required for the growth of numerous tissues and organs and recent evidence indicates that this pathway is often recruited to stimulate growth of cancer stem cells (CSCs) and to orchestrate the reprogramming of cancer cells via epithelial mesenchymal transition (EMT). The objectives of this study were to examine the molecular mechanisms by which (‐)‐epigallocatechin‐3‐gallate (EGCG), an active compound in green tea, inhibits self‐renewal capacity of pancreatic CSCs and synergizes with quercetin, a major polyphenol and flavonoid commonly detected in many fruits and vegetables. Our data demonstrated that EGCG inhibited the expression of pluripotency maintaining transcription factors (Nanog, c‐Myc and Oct‐4) and self‐renewal capacity of pancreatic CSCs. Inhibition of Nanog by shRNA enhanced the inhibitory effects of EGCG on self‐renewal capacity of CSCs. EGCG inhibited cell proliferation and induced apoptosis by inhibiting the expression of Bcl‐2 and XIAP and activating caspase‐3. Interestingly, EGCG also inhibited the components of SHh pathway (smoothened, patched, Gli1 and Gli2) and Gli transcriptional activity. Furthermore, EGCG inhibited EMT by inhibiting the expression of Snail, Slug and ZEB1, and TCF/LEF transcriptional activity, which correlated with significantly reduced CSC's migration and invasion, suggesting the blockade of signaling involved in early metastasis. Furthermore, combination of quercetin with EGCG had synergistic inhibitory effects on self‐renewal capacity of CSCs through attenuation of TCF/LEF and Gli activities. Since aberrant SHh signaling occurs in pancreatic tumorigenesis, therapeutics that target SHh pathway may improve the outcomes of patients with pancreatic cancer by targeting CSCs.
AT9283, a novel aurora kinase inhibitor, suppresses tumor growth in aggressive B‐cell lymphomas
Authors: Qi Wenqing , Liu Xiaobing , Cooke Laurence S. , Persky Daniel O. , Miller Thomas P. , Squires Matthew , Mahadevan Daruka
Published: July 2011

Aurora kinases are oncogenic serine/threonine kinases that play key roles in regulating the mitotic phase of the eukaryotic cell cycle. Auroras are overexpressed in numerous tumors including B‐cell non‐Hodgkin's lymphomas and are validated oncology targets. AT9283, a pan‐aurora inhibitor inhibited growth and survival of multiple solid tumors in vitro and in vivo. In this study, we demonstrated that AT9283 had potent activity against Aurora B in a variety of aggressive B‐(non‐Hodgkin lymphoma) B‐NHL cell lines. Cells treated with AT9283 exhibited endoreduplication confirming the mechanism of action of an Aurora B inhibitor. Also, treatment of B‐NHL cell lines with AT9283 induced apoptosis in a dose and time dependent manner and inhibited cell proliferation with an IC50 < 1 μM. It is well known that inhibition of auroras (A or B) synergistically enhances the effects of microtubule targeting agents such as taxanes and vinca alkaloids to induce antiproliferation and apoptosis. We evaluated whether AT9283 in combination with docetaxel is more efficient in inducing apoptosis than AT9283 or docetaxel alone. At very low doses (5 nM) apoptosis was doubled in the combination (23%) compared to AT9283 or docetaxel alone (10%). A mouse xenograft model of mantle cell lymphoma demonstrated that AT9283 at 15 mg/kg and docetaxel (10 mg/kg) alone had modest anti‐tumor activity. However, AT9283 at 20 mg/kg and AT9283 (15 or 20 mg/kg) plus docetaxel (10 mg/kg) demonstrated a statistically significant tumor growth inhibition and enhanced survival. Together, our results suggest that AT9283 plus docetaxel may represent a novel therapeutic strategy in B‐cell NHL and warrant early phase clinical trial evaluation.
Horizontal transmission and retention of malignancy, as well as functional human genes, after spontaneous fusion of human glioblastoma and hamster host cells in vivo
Authors: Goldenberg David M. , Zagzag David , Heselmeyer‐Haddad Kerstin M. , Berroa Garcia Lissa Y. , Ried Thomas , Loo Meiyu , Chang Chien‐Hsing , Gold David V.
Published: July 2011

Cell fusion in vitro has been used to study cancer, gene mapping and regulation, and the production of antibodies via hybridomas. However, in‐vivo heterosynkaryon formation by cell–cell fusion has received less attention. This investigation describes the spontaneous fusion of a human glioblastoma with normal hamster cells after xenogeneic transplantation, resulting in malignant cells that express both human and hamster genes and gene products, and retention of glioblastoma traits with an enhanced ability to metastasize. Three of 7 human genes found showed translation of their proteins during serial propagation in vivo or in vitro for years; namely, CD74, CXCR4 and PLAGL2, each implicated with malignancy or glioblastoma. This supports the thesis that genetic hybridization of cancer and normal cells can transmit malignancy and also, as first described herein, regulatory genes involved in the tumor's organotypic morphology. Evidence also is increasing that even cell‐free human cancer DNA can induce malignancy and transfer genetic information to normal cells. Hence, we posit that the transfer of genetic information between tumor and stromal cells, whether by cell–cell fusion or other mechanisms, is implicated in the progression of malignancy, and may further define the crosstalk between cancer cells and their stromal neighbors.
Dermatopontin: A potential predictor for metastasis of human oral cancer
Authors: Yamatoji Masanobu , Kasamatsu Atsushi , Kouzu Yukinao , Koike Hirofumi , Sakamoto Yosuke , Ogawara Katsunori , Shiiba Masashi , Tanzawa Hideki , Uzawa Katsuhiro
Published: July 2011

Dermatopontin (DPT), a component of the extracellular matrix (ECM), is involved in promotion of cellular adhesion and ECM assembly activities. However, the role of DPT in the pathogenesis of carcinoma is unclear. We evaluated DPT expression in human oral cancer and its possible roles including cellular adhesion and invasiveness. We first investigated the DPT mRNA and protein expression status in human oral squamous cell carcinoma (OSCC)‐derived cells. Real‐time quantitative reverse transcriptase‐polymerase chain reaction (qRT‐PCR) and immunoblotting analysis detected frequent downregulation of DPT in OSCC‐derived cells compared to human normal oral keratinocytes. To assess the epigenetic regulation of DPT, OSCC‐derived cells were treated with a histone deacetylase inhibitor, sodium butyrate (NaB). NaB restored the DPT expression in OSCC‐derived cells. DPT‐overexpressed cells were examined whether DPT could contribute to cellular adhesion and invasiveness. Markedly, increased adhesion and decreased invasiveness in DPT‐overexpressed cells were found compared to mock‐transfected cells. Adhesion of DPT‐overexpressed cells was inhibited by α3β1 integrin functional blocking antibody. OSCC‐derived cells treated with NaB also decreased invasiveness. The expression status of DPT in primary OSCCs (n = 97) was analyzed and compared to clinicopathological behavior. DPT expression in primary OSCCs was significantly lower (p < 0.05) than in the normal counterparts and was correlated significantly (p < 0.05) with regional lymph node metastasis. Our data provided strong evidence that downregulation of DPT is a characteristic event in OSCCs and that DPT was correlated with cellular adhesion and invasiveness. Therefore, DPT might play an important role in regulating tumor invasion and metastasis.
A million africans a year dying from cancer by 2030: What can cancer research and control offer to the continent?
Authors: Sylla Bakary S. , Wild Christopher P.
Published: July 2011

In Africa, there were an estimated 681,000 new cancer cases and 512,000 deaths in 2008. Projections to 2030 show a startling rise, with corresponding figures of 1.27 million cases and 0.97 million deaths resulting from population growth and aging alone. The figures make no assumptions about incidence rates which may increase due to the further introduction of tobacco and a more westernized lifestyle. The current situation in many parts of Africa with respect to health care systems suggests that improved cancer treatment would be an insufficient response to this increasing burden. Much could be achieved through cancer prevention by applying current knowledge about major risk factors and the natural history of the disease. For example, vaccination against hepatitis B virus and human papilloma viruses would prevent the occurrence of two of the most common cancers in Africa, liver and cervix, respectively, in the long‐term. Strong measures to prevent the widespread introduction of tobacco must be a priority. Early detection and treatment of cervical and breast cancers using approaches applicable now in Africa would provide immediate value, as would the management of human immunodeficiency virus (HIV) infection in respect to HIV‐associated malignancies. In parallel, further research is needed into the causes of cancer and the barriers to implementation of promising prevention strategies. Underpinning all is the need for African governments to look forward and prioritize cancer through national cancer control plans, to invest in public health infrastructure and to ensure the adequate training and support for people in cancer prevention and control. Given this core commitment from within Africa, international partners can provide complementary support in a cooperation that permits action now to mitigate the impending tragedy of cancer in the continent of Africa.
Novelties That Change Carrying Capacity
Authors: Erwin Douglas H.
Published: July 2011

Comparative developmental studies have revealed a rich array of details about the patterns and processes of morphological change in animals and increasingly in plants. But, applying these insights to the study of major episodes of evolutionary innovation requires understanding how these novel morphologies become established and sufficiently abundant (either as individuals within a species or as a clade of species) to be preserved in the fossil record, and, in many cases, to influence ecological processes. Evolutionary novelties may: (1) disappear without changing the species; (2) be associated with the generation (through selection or drift) of a new species; and if the latter (3) may or may not become ecologically significant. Only the latter are commonly preserved in the fossil record. These alternatives mirror the distinction among historians of technology between innovation and invention. Here, I argue that specific sorts of evolutionary inventions drive ecological transformation, essentially constructing an environment for themselves and ancillary organisms through ecological spillover effects, increasing the “carrying capacity” of an ecosystem. J. Exp. Zool. (Mol. Dev. Evol.) 318B:460–465, 2012. © 2011 Wiley Periodicals, Inc.
A new conjugated addition of trialkyl phosphites and alkylidenephosphoranes to 3‐ω‐azideoacetyl coumarin synthesis of some 1,2,3,4‐triazaphospholes, triazoles, and azido‐coumarin derivatives
Authors: Sediek Ashraf A. , Shaddy Abeer A. , Abdou Wafaa M.
Published: July 2011

A new and efficient conjugate addition of trimethyl and triethyl phosphites to 3‐ω‐azidoacetylcoumarin (1) has been studied. The reaction proceeded smoothly at r.t. furnishing 1,2,3,4‐triazaphosphole coumarin derivatives 4a, 4b in ∼75% yields. Linear substituted triazoles 10b, 11a were also obtained from the reactions of 1 with α‐keto ylides, acetyl‐ and benzoylmethylene triphenylphosphoranes. Contrary to these results, Wittig reaction was occurred when 1 was allowed to react with α‐alkoxycarbonylmethylene‐ and cyanomethylenetriphenylphosphoranes 7c, 7d, 7e as well as with methylidene‐ and benzylidenetriphenylphosphoranes 8b, 10a resulting in the formation of the corresponding olefins either as an intermediate 14b or as final products 11b, 11c, 12a. J. Heterocyclic Chem., (2011).
Sexual orientation harassment in the workplace: When do observers intervene?
Authors: Ryan Ann Marie , Wessel Jennifer Leah
Published: July 2011

Little is known about when and why observers of harassment incidents choose to intervene. On the basis of a model of observer intervention by Bowes‐Sperry and O'Leary‐Kelly (2005), we examined situational (directness of harassment, relationship to target, knowledge of target orientation, recurrence beliefs) variables as potential predictors of observer decisions to intervene when witnessing sexual orientation harassment. We also examined how costs and benefits analysis and recurrence beliefs relate to the level and immediacy of involvement. Relationship to the target, directness of the harassment, recurrence beliefs, knowledge of target orientation, and costs evidenced some connections to the nature of intervention. We discussed implications for organizations. Copyright © 2011 John Wiley & Sons, Ltd.
Growth potential of different zones of the growth plate—an experimental study in rabbits
Authors: Hajdu Stefan , Schwendenwein Elisabeth , Kaltenecker Gerhard , László Ilonka , Lang Susanna , Vécsei Vilmos , Sarahrudi Kambiz
Published: July 2011

Despite clinical efforts to treat growth disturbances only little is known about the growth potential of the different zones of the growth plate. The aim of this study was to investigate the growth potential of different zones of the growth plate. A total of 20 New Zealand White rabbits were used for this experiment. The right and left ulna of each animal were used resulting in a total of 40 ulnae. Animals were assigned into five groups. In groups I and II resection of the metaphyseal (n = 12) or the epiphyseal (n = 6) segment of the growth plate was performed. In group III resection of the growth plate and re‐implantation was performed (n = 6). In group IV the growth plate was resected and re‐implanted after a 180° rotation (n = 6). Animals in group V served as controls. Histologic and radiologic examinations were performed to evaluate the growth process at 1, 2, 4, and 12 weeks following surgery. In group I, III, and IV temporary growth disturbance which was compensated within a short time was observed. Resection of the epiphyseal part resulted in growth arrest of the distal ulna in combination with normal growth of the radius which led to and valgus deformity of the limb. The results of this study indicate the importance of the reserve zone for the functioning of the growth plate. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:162–168, 2012
Effectiveness of Zataria multiflora Boiss essential oil and grape seed extract impregnated chitosan film on ready‐to‐eat mortadella‐type sausages during refrigerated storage
Authors: Moradi Mehran , Tajik Hossein , Razavi Rohani Seyed Mehdi , Oromiehie Abdul Rasoul
Published: July 2011

BACKGROUND: The effectiveness of chitosan films containing Zataria multiflora Boiss essential oil (ZEO) (5 and 10 g kg−1) and grape seed extract (GSE) (10 g kg−1) on lipid oxidation and microbial (lactic acid bacteria, aerobic mesophiles and inoculated Listeria monocytogenes) characteristics of mortadella sausage at 4 °C for 21 days was evaluated. The release of total phenolics (TPs) into sausage was also assessed.

RESULTS: All films exhibited antibacterial activity against L. monocytogenes on agar culture media. Chitosan films containing ZEO were the most effective on the growth of bacteria. The growth of L. monocytogenes was significantly inhibited by ZEO‐GSE containing films especially during storage of the sausages for 6 days. Aerobic mesophiles and lactic acid bacteria were the most sensitive and resistant groups to films by 0.1–1.1 and 0.1–0.7 log cycles reduction, respectively. Sausages wrapped by 10 g kg−1 GSE + 10 g kg−1 ZEO films had the lowest degrees of lipid oxidation, which was 23% lower than the control. The TPs of ZEO films decreased to zero after 6 days, whereas TPs of GSE films followed a slight decrease during the storage.

CONCLUSION: Antimicrobial/antioxidant chitosan film could be developed by incorporating GSE and ZEO for extending the shelf life of mortadella sausage. Copyright © 2011 Society of Chemical Industry
Influence of fertilisation regimes on a nosZ‐containing denitrifying community in a rice paddy soil
Authors: Chen Zhe , Hou Haijun , Zheng Yan , Qin Hongling , Zhu Yijun , Wu Jinshui , Wei Wenxue
Published: July 2011

BACKGROUND: Denitrification is a microbial process that has received considerable attention during the past decade since it can result in losses of added nitrogen fertilisers from agricultural soils. Paddy soil has been known to have strong denitrifying activity, but the denitrifying microorganisms responsible for fertilisers in paddy soil are not well known. The objective of this study was to explore the impacts of 17‐year application of inorganic and organic fertiliser (rice straw) on the abundance and composition of a nosZ‐denitrifier community in paddy soil. Soil samples were collected from CK plots (no fertiliser), N (nitrogen fertiliser), NPK (nitrogen, phosphorus and potassium fertilisers) and NPK + OM (NPK plus organic matter). The nitrous oxide reductase gene (nosZ) community composition was analysed using terminal restriction fragment length polymorphism, and the abundance was determined by quantitative PCR.

RESULTS: Both the largest abundance of nosZ‐denitrifier and the highest potential denitrifying activity (PDA) occurred in the NPK + OM treatment with about four times higher than that in the CK and two times higher than that in the N and NPK treatments (no significant difference). Denitrifying community composition differed significantly among fertilisation treatments except for the comparison between CK and N treatments. Of the measured abiotic factors, total organic carbon was significantly correlated with the observed differences in community composition and abundance (P < 0.01 by Monte Carlo permutation).

CONCLUSION: This study shows that the addition of different fertilisers affects the size and composition of the nosZ‐denitrifier community in paddy soil. Copyright © 2011 Society of Chemical Industry
High‐sensitivity capillary and microchip electrophoresis using electrokinetic supercharging
Authors: Dawod Mohamed , Chung Doo Soo
Published: July 2011

Electrokinetic supercharging (EKS) is considered as one of the most powerful online preconcentration techniques in electrophoresis. It combines the efficient preconcentration power of field‐amplified sample injection and the exceptional selective nature of transient isotachophoresis. It has a wide range of applications to different types of analytes ranging from small ions to large proteins and DNA fragments. This comprehensive review — up to date — provides listing for all the works, developments, and advances in EKS. The review will pay particular attention to innovations, new methodologies for manipulation, challenges for improving the detection sensitivity, and various applications of EKS in capillaries and microchips.
Grizzly bear selection of avalanche chutes: Testing the effectiveness of forest buffer retention
Authors: Serrouya Robert , Mclellan Bruce N. , Pavan Gary D. , Apps Clayton D.
Published: July 2011

In mountainous areas with sufficient snowfall, avalanche chutes are an important component of grizzly bear (Ursus arctos) habitat. Therefore, regional land‐use plans have recommended retaining adjacent forest buffers to maintain security and thus reduce potential impacts of clearcut forest harvesting. Our objective was to determine if forest buffers affected selection of avalanche chutes by grizzly bears, while accounting for factors such as vegetation composition and other physical attributes. We used radio‐location data from 61 grizzly bears collected between 1994 and 2000 in southern British Columbia, mapped a sample of avalanche chutes (1,045), and quantified the amount of forb, shrub, tree, and non‐vegetated cover within each chute. We also measured forested buffer width on each side of the chute, solar radiation, chute size, chute frequency (no. of chutes/km), and the area of clearcut logging adjacent to chutes. Each avalanche chute was the sample unit and the number of grizzly bear radiolocations was the dependent variable. We found that natural biophysical attributes were the strongest factors predicting the level of avalanche chute use by bears. Frequency of large chutes (>100 m wide), chute area, forb content, and solar radiation all positively affected use by bears. Larger avalanche chutes had a higher proportion of forb cover than smaller chutes, and more of these large chutes per unit area provided increased forage opportunities. Based on multivariate analyses, forested buffer width or the amount of clearcut logging were not strong factors predicting the level of use. However, a post hoc univariate analysis revealed that clearcut logging reduced the amount of bear use of the best avalanche chutes (large and abundant chutes). Furthermore, because a portion of our study area contained logging but no vehicle traffic, we concluded that it was the removal of tree cover, rather than displacement by vehicles, that caused the observed pattern. Although our multivariate models did not perform well using independent validation in a different geographic area, 4 factors were consistently important (large and abundant chutes, forb content, with a negative but weaker influence of clearcutting), suggesting broad applicability of these factors in mountainous ecosystems. © 2011 The Wildlife Society.
Correcting radiofrequency inhomogeneity effects in skeletal muscle magnetisation transfer maps
Authors: Sinclair C. D. J. , Morrow J. M. , Hanna M. G. , Reilly M. M. , Yousry T. A. , Golay X. , Thornton J. S.
Published: July 2011

The potential of MRI to provide quantitative measures of neuromuscular pathology for use in therapeutic trials is being increasingly recognised. Magnetisation transfer (MT) imaging shows particular promise in this context, being sensitive to pathological changes, particularly in skeletal muscle, where measurements correlate with clinically measured muscle strength. Radiofrequency (RF) transmit field (B1) inhomogeneities can be particularly problematic in measurements of the MT ratio (MTR) and may obscure genuine muscle MTR changes caused by disease. In this work, we evaluate, for muscle imaging applications, a scheme previously proposed for the correction of RF inhomogeneity artefacts in cerebral MTR maps using B1 information acquired in the same session. We demonstrate the theoretical applicability of this scheme to skeletal muscle using a two‐pool model of pulsed quantitative MT. The correction scheme is evaluated practically in MTR imaging of the lower limbs of 28 healthy individuals and in two groups of patients with representative neuromuscular diseases: Charcot–Marie–Tooth disease type 1A and inclusion body myositis. The correction scheme was observed to reduce both the within‐subject and between‐subject variability in the calf and thigh muscles of healthy subjects and patient groups in histogram‐ and region‐of‐interest‐based approaches. This method of correcting for RF inhomogeneity effects in MTR maps using B1 data may markedly improve the sensitivity of MTR mapping indices as measures of pathology in skeletal muscle. Copyright © 2011 John Wiley & Sons, Ltd.
Localized 1H NMR spectroscopy in different regions of human brain in vivo at 7 T: T2 relaxation times and concentrations of cerebral metabolites
Authors: Marjańska Małgorzata , Auerbach Edward J. , Valabrègue Romain , Van de Moortele Pierre‐François , Adriany Gregor , Garwood Michael
Published: July 2011

At the high field strength of 7 T, in vivo spectra of the human brain with exceptional spectral quality sufficient to quantify 16 metabolites have been obtained previously only in the occipital lobe. However, neurochemical abnormalities associated with many brain disorders are expected to occur in brain structures other than the occipital lobe. The purpose of the present study was to obtain high‐quality spectra from various brain regions at 7 T and to quantify the concentrations of different metabolites. To obtain concentrations of metabolites within four different regions of the brain, such as the occipital lobe, motor cortex, basal ganglia and cerebellum, the T2 relaxation times of the singlets and J‐coupled metabolites in these regions were measured for the first time at 7 T. Our results demonstrate that high‐quality, quantifiable spectra can be obtained in regions other than the occipital lobe at 7 T utilizing a 16‐channel transceiver coil and B1+ shimming. Copyright © 2011 John Wiley & Sons, Ltd.
Cell‐free fetal DNA testing: a pilot study of obstetric healthcare provider attitudes toward clinical implementation
Authors: Sayres Lauren C. , Allyse Megan , Norton Mary E. , Cho Mildred K.
Published: July 2011

Objective

To provide a preliminary assessment of obstetric healthcare provider opinions surrounding implementation of cell‐free fetal DNA testing.

Methods

A 37‐question pilot survey was used to address questions around the translation and use of non‐invasive prenatal testing using cell‐free fetal DNA. The survey was distributed and collected at a Continuing Medical Education course on obstetrics and gynecology.

Results

Of 62 survey respondents, 73% were female and 87% held MD/DO degrees. Respondents generally agreed that patients want prenatal diagnostic information to help make decisions about a pregnancy and that cell‐free fetal DNA testing would encourage the testing of more patients for more conditions. However, there was an overall lack of knowledge or conviction about using this technology. Genetic counseling and professional society approval were deemed important to implementation, whereas the possibility of direct‐to‐consumer testing and government regulation produced mixed responses. Respondents indicated that they would be more likely to offer cell‐free fetal DNA testing for chromosomal abnormalities and single‐gene disorders, but would be cautious with respect to determination of sex and behavioral or late‐onset conditions.

Conclusion

Preliminary assessment indicates uncertainty among obstetric providers about the details of implementing cell‐free fetal DNA testing and suggests expanded research on perspectives of this stakeholder group. Copyright © 2011 John Wiley & Sons, Ltd.
Methodological challenges in the coding and adjudication of sudden deaths in a large simple trial with observational follow‐up: the ziprasidone observational study of cardiac outcomes (ZODIAC)
Authors: Geier Jamie L. , Karayal Onur N. , Lewis Michael , Camm John A. , Keane Martin , Kremer Charlotte ME. , Kolluri Sheela , Reynolds Robert , Eng Sybil , Strom Brian L.
Published: July 2011

Purpose

The Ziprasidone Observational study of car DIAC Outcomes (ZODIAC), a large simple trial comparing ziprasidone versus olanzapine in real‐world use, showed no difference in risk of sudden death. Upon the request of the US Food and Drug Administration, 205 fatal events were readjudicated applying ICD‐10 coding rules for sudden death.

Methods

A readjudication committee coded three domains (witness to death, time of symptom onset to death, and most likely cause of death) for use within algorithms consistent with ICD‐10 rules. Relative risks (RR) and corresponding 95%CI were calculated for persons randomized to ziprasidone versus olanzapine, comparing 1‐year incidence of sudden death, using multiple definitions.

Results

Data on symptom onset to death and diagnosis of specific cardiac arrhythmias required by the ICD‐10 rules were often lacking. Sensitivity analyses were conducted to explore the impact of cases suggestive of cardiac origin but missing data required by ICD‐10 sudden death codes. Overall, the readjudicated data matched the study's initial findings, with no significant difference in 1‐year mortality between ziprasidone and olanzapine for sudden death not otherwise specified and sudden cardiac death (R96.0 or R96.1 or I46.1; RR = 1.11, 95%CI 0.45– 2.77).

Conclusions

After outcome readjudication, ZODIAC found no difference in the risk of sudden death among those randomized to ziprasidone versus olanzapine. However, unlike hospital‐based studies, fatal events in general population studies often occur outside hospital and often lack the clinical detail needed for the exact determination of symptom onset and event. Epidemiological evaluations of sudden death need to consider the limitations of the available data. Copyright © 2011 John Wiley & Sons, Ltd.
Is less more? Patients' preferences for drug information leaflets
Authors: Schwappach David L.B. , Mülders Verena , Simic Dusan , Wilm Stefan , Thürmann Petra A.
Published: July 2011

Purpose

Present package information leaflets do not fulfil the needs of many patients. The objective of this study was to investigate patients' preferences towards content and presentation of drug information leaflets using prepared medication brochures in a discrete choice experiment.

Methods

6 binary attributes relating to content and presentation of drug information were used to define and design alternative leaflets. Choice sets between alternative leaflets were created based on an orthogonal design. 1,000 participants aged at least 50 years were presented 8 choice sets of drug information leaflets in a personal interview. The reliability of choices was assessed with a duplicate of one original choice. Regression analysis was used to model the impact of attributes on choices and interactions with responders' age and education.

Results

Participants slightly preferred colored over black‐white leaflets, no visual presentation of side effects by the use of smilies, the provision of a brief summary, and general health tips, but no information on what‐to‐do in case of side‐effects. All attributes except the " extent of side‐effects presented" significantly affected participants' choices. Older and less educated participants preferred less information. Of the repeated (duplicate) choices, 84% were replicates of the original choice. Interrater agreement was moderate (K = 0.67, CI 0.6 ‐ 0.7). 235 subjects (23.5%) followed an optimization strategy and did not trade attributes, i.e., exhibited dominant preferences.

Conclusions

In general, participants preferred condensed, plain information in a clear and moderately colored design, but preferences towards drug information are affected by age and level of education. Copyright © 2011 John Wiley & Sons, Ltd.
Polypharmacy of potentially addictive medication in the older persons—quantifying usage
Authors: Ineke Neutel C. , Skurtveit Svetlana , Berg Christian
Published: July 2011

Purpose

The use of restricted medications, for example, opioids, benzodiazepines (BZD), and z‐hypnotics, in the older persons continues to increase. Little is known about usage practices or about the extent of polypharmacy within this group. The objectives of this study were (i) to describe polypharmacy and (ii) to develop a medication usage index (MUI) to quantify usage patterns.

Methods

Data for 2008 were obtained from the Norwegian Prescription Database containing all prescriptions filled in Norwegian pharmacies. The study population included people aged 70–89 years who filled prescriptions for weak opioids, strong opioids, anxiolytic BZD, hypnotic BZD, and/or z‐hypnotics. A MUI was developed based on Anatomical Therapeutic Chemical codes, defined daily doses, Anatomical Therapeutic Chemical subgroups, and number of prescribers.

Results

Forty‐two percent of elderly Norwegians filled at least one prescription in one of the medication subgroups in 2008. MUI Level 1 (least) usage was shown by 56.6% of users (23.8% of the general population), Level 2 by 29.7% (12.5%), Level 3 by 11.3% (4.8%), and Level 4 (most) by 2.4% (1.0%). People using strong opioids were the most likely to use other restricted medications. In addition, female participants had a higher MUI than did male participants, and older users higher than younger users. Cancer or palliative care patients attained twice the MUI points than did the others.

Conclusions

Polypharmacy was found to be common within these restricted drug categories for the older persons. MUI provides a convenient approach to summarizing drug usage and will be useful in detecting trends and regional differences and determining the impact of interventions. Copyright © 2011 John Wiley & Sons, Ltd.
Application of Amorphous Boron Granulated With Hydroxyl‐ Terminated Polybutadiene in Fuel‐Rich Solid Propellant
Authors: Pang Weiqiang , Fan Xuezhong , Zhang Wei , Xu Huixiang , Li Jizhen , Li Yonghong , Shi Xiaobing , Li Yang
Published: July 2011

Amorphous boron powder granulated with HTPB, whose particle diameter could be controlled, was prepared by mechanical mill method. It was found that amorphous boron powder could be granulated with HTPB binder to form B‐HTPB particles, whose median particle diameter (d50) and specific surface area are in the range of 125.0–431.0 µm and 0.02–0.1 m2 g−1, respectively. The B‐HTPB particles could be dispersed in the HTPB binder with relatively low viscosity compared with direct addition of amorphous boron powder to the HTPB binder. The experimental results showed that the content of boron particles in a fuel‐rich propellant could be increased by addition of B‐HTPB particles and the combustion characteristics of the fuel‐rich solid propellant could be improved.
Investigation on the Thermal Expansion and Theoretical Density of 1,3,5‐Trinitro‐1,3,5‐Triazacyclohexane
Authors: Sun Jie , Shu Xiaoyan , Liu Yu , Zhang Haobin , Liu Xiaofeng , Jiang Yan , Kang Bin , Xue Chao , Song Gongbao
Published: July 2011

The CTE and the theoretical density are important properties for energetic materials. To obtain the CTE and the theoretical density of 1,3,5‐trinitro‐1,3,5‐triazacyclohexane (RDX), XRD, and Rietveld refinement are employed to estimate the dimensional changes, within the temperature range from 30 to 170 °C. The CTE of a, b, c axis and volume are obtained as 3.07×10−5 K−1, 8.28×10−5 K−1, 9.19×10−5 K−1, and 20.7×10−5 K−1, respectively. Calculated from the refined cell parameters, the theoretical density at the given temperature can be obtained. The theoretical density at 20 °C (1.7994 g cm−3) is in close match with the RDX single‐crystal density (1.7990 g cm−3) measured by density gradient method. It is suggested that the CTE measured by XRD could perfectly meet with the thermal expansion of RDX.
Prostate carcinoma cells LNCaP and glucan cooperate in induction of cytokine synthesis by dendritic cells: Effect on natural killer cells and CD4+ lymphocytes activation
Authors: Donini Marta , Marongiu Laura , Fontana Emanuela , Dusi Stefano
Published: July 2011

BACKGROUND

Glucan is an immunomodulating agent used for cancer therapy. We investigated the effects of glucan on immune cell response to prostate carcinoma.

METHODS

Dendritic cells (DC) were co‐cultured with prostate carcinoma cells LNCaP and/or glucan, and maturation markers expression, cytokine release, and superoxide anion production were evaluated. Conditioned media from glucan‐treated or untreated DC and/or LNCaP cultures were used to stimulate T lymphocytes and natural killer (NK) cells.

RESULTS

LNCaP promoted partial DC maturation and scarce IL‐12 secretion. Glucan induced DC maturation but no IL‐12 production by DC. However, glucan increased IL‐12 release by DC co‐cultured with LNCaP. Moreover, LNCaP enhanced IL‐1β, IL‐23, IL‐6, and TNF‐α secretion, but decreased superoxide anion production in glucan‐stimulated DC. The NADPH oxidase inhibitor diphenyliodonium chloride (DPI) and the superoxide anion scavenger superoxide dismutase (SOD) reproduced this effect, but did not affect IL‐12 secretion. Conditioned media of glucan‐treated DC/LNCaP co‐cultures activated IFN‐γ production by NK cells and Th1/Th17 generation by CD4+ lymphocytes, whereas media from DC/LNCaP co‐cultured without glucan produced scarce NK and CD4+ cells responses. Experiments performed with an IL‐12‐blocking antibody demonstrated that these effects arise from glucan‐dependent regulation of IL‐12 production by DC.

CONCLUSIONS

Glucan and LNCaP cooperate in induction of cytokine synthesis by DC. LNCaP enhance IL‐1β, IL‐23, IL‐6, and TNF‐α secretion by decreasing glucan‐dependent NADPH oxidase activity, whereas glucan increases IL‐12 production through NADPH oxidase‐unrelated mechanisms. This cooperation is essential to elicit a substantial NK cells and CD4+ lymphocytes activity, pointing out a potential relevance of glucan in prostate cancer therapy. Prostate 72:566–576, 2012. © 2011 Wiley Periodicals, Inc.
The curcumin analog ca27 down‐regulates androgen receptor through an oxidative stress mediated mechanism in human prostate cancer cells
Authors: Fajardo Alexandra M. , MacKenzie Debra A. , Ji Ming , Deck Lorraine M. , Jagt David L. Vander , Thompson Todd A. , Bisoffi Marco
Published: July 2011

BACKGROUND

The androgen receptor (AR) plays a critical role in prostate cancer development and progression. Therefore, the inhibition of AR function is an established therapeutic intervention. Since the expression of the AR is retained and often increased in progressive disease, AR protein down‐regulation is a promising therapeutic approach against prostate cancer. We show here that the curcumin analog 27 (ca27) down‐regulates AR expression in several prostate cancer cell lines.

METHODS

ca27 at low micromolar concentrations was tested for its effect on AR expression, AR activation, and induction of oxidative stress in human LNCaP, C4‐2, and LAPC‐4 prostate cancer cells.

RESULTS

ca27 induced the down‐regulation of AR protein expression in LNCaP, C4‐2, and LAPC‐4 cells within 12 hr. Further, ca27 led to the rapid induction of reactive oxygen species (ROS). To further support this finding, ca27 treatment led to the activation of the cellular redox sensor NF‐E2‐related factor 2 (Nrf2) and the induction of the Nrf2‐regulated genes NAD(P)H quinone oxidoreductase 1 and aldoketoreductase 1C1. We show that ROS production preceded AR protein loss and that ca27‐mediated down‐regulation of the AR was attenuated by the antioxidant, N‐acetyl cysteine.

CONCLUSIONS

ca27 induces ROS and mediates AR protein down‐regulation through an oxidative stress mechanism of action. Our results suggest that ca27 represents a novel agent for the elucidation of mechanisms of AR down‐regulation, which could lead to effective new anti‐androgenic strategies for the treatment of advanced prostate cancer. Prostate 72:612–625, 2012. © 2011 Wiley Periodicals, Inc.
Does Labour Migration Offer Opportunities for Meeting Prospective Spouses? The Case of Migrant Workers in Cambodia
Authors: Yagura Kenjiro
Published: July 2011

In the rural areas of developing countries, the children of poor families are at a disadvantaged position in the local marriage market. Labour migration may offer opportunities to find a suitable spouse because an acquaintance in the migration destination may emerge as a prospective spouse. This paper examines whether or not this happens in reality. Econometric analysis of the data of unmarried migrant workers in Phnom Penh indicated that those who do not expect their parents to give them land prefer marrying someone they meet in Phnom Penh rather than someone from their own place of origin. This suggests that those who encounter difficulties in finding a partner in their place of origins actively seek a spouse at the migration destination. The findings indicate that labour migration introduces changes in the formation of families, which consequently influences familial relationships. Copyright © 2011 John Wiley & Sons, Ltd.
Hafnia nanoparticles – a model system for graphene growth on a dielectric
Authors: Kidambi Piran R. , Bayer Bernhard C. , Weatherup Robert S. , Ochs Rolf , Ducati Caterina , Szabó D. Vinga , Hofmann Stephan
Published: July 2011

We study graphene growth on hafnia (HfO2) nanoparticles by chemical vapour deposition using optical microscopy, high resolution transmission electron microscopy and Raman spectroscopy. We find that monoclinic HfO2 nanoparticles neither reduce to a metal nor form a carbide while nucleating nanometer domain‐sized few layer graphene. Hence we regard this as an interesting non‐metallic catalyst model system with the potential to explore graphene growth directly on a (high‐k) dielectric.

magnified image

HfO2 nanoparticles coated with few layer graphene by atmospheric pressure CVD with methane and hydrogen at 950 °C.

(© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)