bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel method to enhance informed consent: a prospective and randomised trial of form-based versus electronic assisted informed consent in paediatric endoscopy
Authors: Friedlander Joel A , Loeben Greg S , Finnegan Patricia K , Puma Anita E , Zhang Xuemei , de Zoeten Edwin F , Piccoli David A , Mamula Petar 
Published: January 2011

ObjectivesTo evaluate the adequacy of paediatric informed consent and its augmentation by a supplemental computer-based module in paediatric endoscopy.MethodsThe Consent-20 instrument was developed and piloted on 47 subjects. Subsequently, parents of 101 children undergoing first-time, diagnostic upper endoscopy performed under moderate IV sedation were prospectively and consecutively, blinded, randomised and enrolled into two groups that received either standard form-based informed consent or standard form-based informed consent plus a commercial (Emmi Solutions, Inc, Chicago, Il), sixth grade level, interactive learning module (electronic assisted consent). Anonymously and electronically, the subjects' anxiety (State Trait Anxiety Inventory), satisfaction (Modified Group Health Association of America), number of questions asked, and attainment of informed consent were assessed (Consent-20). Statistics were calculated using t test, paired t test, and Mann Whitney tests.ResultsThe ability to achieve informed consent, as measured by the new instrument, was 10% in the control form-based consent group and 33% in the electronic assisted consent group (p<0.0001). Electronically assisting form-based informed consent did not alter secondary outcome measures of subject satisfaction, anxiety or number of questions asked in a paediatric endoscopy unit.ConclusionsThis study demonstrates the limitations of form-based informed consent methods for paediatric endoscopy. It also shows that even when necessary information was repeated electronically in a comprehensive and standardised video, informed consent as measured by our instrument was incompletely achieved. The supplemental information did, however, significantly improve understanding in a manner that did not negatively impact workflow, subject anxiety or subject satisfaction. Additional study of informed consent is required.Clinical trial registration numberClinicalTrials.gov IdentifierNCT00899392.
Fine structure of helium and light helium-like ionsThis paper was presented at the International Conference on Precision Physics of Simple Atomic Systems, held at École de Physique, les Houches, France, 30 May – 4 June, 2010.
Authors: Pachucki Krzysztof , Yerokhin Vladimir A. 
Published: January 2011

Calculational results are presented for the fine structure splitting of the 23P state of helium and helium-like ions with nuclear charge Z up to 10. Theoretical predictions are in agreement with the latest experimental results for the helium fine structure intervals as well as with the most of the experimental data available for light helium-like ions. Comparing the theoretical value of the 23P0-23P1 interval in helium with experimental results (Zelevinsky et al. Phys. Rev. Lett. 95, 203001 (2005)), we determine the value of the fine structure constant α with an accuracy of 31 ppb.
Progress in precise laser spectroscopy of antiprotonic helium atomsThis paper was presented at the International Conference on Precision Physics of Simple Atomic Systems, held at École de Physique, les Houches, France, 30 May – 4 June, 2010.
Authors: Hori Masaki 
Published: January 2011

The ASACUSA collaboration at CERN has previously measured the optical transition frequencies of antiprotonic helium to a precision of <1 part in 108 by laser spectroscopy. We describe some recent theoretical and experimental developmental work carried out by our collaboration to further improve the experimental precision.
Hyperfine interaction effects on the (1s2p)3P1–(1s2s)1S0 energy splitting in He-like ions for parity nonconservation studiesThis paper was presented at the International Conference on Precision Physics of Simple Atomic Systems, held at École de Physique, les Houches, France, 30 May – 4 June, 2010.
Authors: Ferro Fabrizio , Artemyev Anton , Surzhykov Andrey , Stöhlker Thomas 
Published: January 2011

Accurate theoretical knowledge of the (1s2p)3P1–(1s2s)1S0 splitting in He-like ions is demanded for future experimental studies of the nuclear spin-dependent part of the weak interaction. In this paper we perform a calculation of the hyperfine structure of (1s2p)3P1–(1s2s)1S0 within 3 ≤ Z ≤ 35, Z being the atomic number. In this Z range parity nonconservation (PNC) effects are amplified by the close energy proximity of the opposite parity levels (1s2p)3P1 and (1s2s)1S0. We find that the hyperfine structure is relevant for Z > 12, and produces splitting among the hyperfine sublevels as large as 150 meV for medium Z He-like ions (Z ∼ 35).
Particle dark matter in the galactic halo: recent results from DAMA/LIBRAThis paper was presented at the International Conference on Precision Physics of Simple Atomic Systems, held at École de Physique, les Houches, France, 30 May – 4 June, 2010.
Authors: Bernabei R. , Belli P. , Montecchia F. , Nozzoli F. , Cappella F. , d’Angelo A. , Incicchitti A. , Prosperi D. , Cerulli R. , Dai C. J. , He H. L. , Ma X. H. , Sheng X. D. , Wang R. G. , Ye Z. P. 
Published: January 2011

The DAMA/LIBRA experiment has a sensitive mass of about 250 kg highly radiopure NaI(Tl). It is running at the Gran Sasso National Laboratory of the INFN in Italy and is mainly devoted to the investigation of dark matter (DM) particles in the galactic halo by exploiting the model-independent DM annual modulation signature. The present DAMA/LIBRA and the former DAMA/NaI experiments (the first generation experiment having an exposed mass of about 100 kg) have thus far cumulatively released the results of data collected over 13 annual cycles (total exposure: 1.17 t year). They give model-independent evidence of the presence of DM particles in the galactic halo on the basis of the investigated DM signature at 8.9 σ C.L. for the cumulative exposure. The main aspects of the obtained results are summarized and some comments are addressed.
Advances towards a new measurement of the 1S–2S transition of positroniumThis paper was presented at the International Conference on Precision Physics of Simple Atomic Systems, held at École de Physique, les Houches, France, 30 May – 4 June, 2010.
Authors: Crivelli P. , Cesar C. L. , Gendotti U. 
Published: January 2011

In this paper, a new experiment is presented to measure the 1S–2S transition of positronium, the bound state of an electron and a positron. The goal is to improve the current accuracy by a factor of 5 to reach a precision of the order of 0.6 ppb, to check recent QED calculations. This accuracy is challenging, but it seems well within reach in view of the technological advances that have occurred during the last two decades. We will present the details of the experimental set-up, the advances in the production of positronium, the developments of the laser system, and as well our new experimental technique for the detection of Ps in the 2S state.
Notch3 Activation Promotes Invasive Glioma Formation in a Tissue Site-Specific Manner
Authors: Pierfelice Tarran J. , Schreck Karisa C. , Dang Louis , Asnaghi Laura , Gaiano Nicholas , Eberhart Charles G. 
Published: January 2011

Abstract
Although Notch signaling has been widely implicated in neoplastic growth, direct evidence for in vivo initiation of neoplasia by the pathway in murine models has been limited to tumors of lymphoid, breast, and choroid plexus cells. To examine tumorigenic potential in the eye and brain, we injected retroviruses encoding activated forms of Notch1, Notch2, or Notch3 into embryonic mice. Interestingly, the majority of animals infected with active Notch3 developed proliferative lesions comprised of pigmented ocular choroid cells, retinal and optic nerve glia, and lens epithelium. Notch3-induced lesions in the choroid, retina, and optic nerve were capable of invading adjacent tissues, suggesting that they were malignant tumors. Although Notch3 activation induced choroidal tumors in up to 67% of eyes, Notch1 or Notch2 activation never resulted in such tumors. Active forms of Notch1 and Notch2 did generate a few small proliferative glial nodules in the retina and optic nerve, whereas Notch3 was 10-fold more efficient at generating growths, many of which were large invasive gliomas. Expression of active Notch1/Notch3 chimeric receptors implicated the RBPjk-association molecule and transactivation domains of Notch3 in generating choroidal and glial tumors, respectively. In contrast to our findings in the optic nerve and retina, introduction of active Notch receptors, including Notch3, into the brain never caused glial tumors. Our results highlight the differential ability of Notch receptor paralogs to initiate malignant tumor formation, and suggest that glial precursors of the optic nerve, but not the brain, are susceptible to transformation by Notch3. Cancer Res; 71(3); 1115–25. ©2011 AACR.
Alpha- versus Beta-Particle Radiopeptide Therapy in a Human Prostate Cancer Model (213Bi-DOTA-PESIN and 213Bi-AMBA versus177Lu-DOTA-PESIN)
Authors: Wild Damian , Frischknecht Michael , Zhang Hanwen , Morgenstern Alfred , Bruchertseifer Frank , Boisclair Julie , Provencher-Bolliger Anne , Reubi Jean-Claude , Maecke Helmut R. 
Published: January 2011

Abstract
Recurrent prostate cancer presents a challenge to conventional treatment, particularly so to address micrometastatic and small-volume disease. Use of α-radionuclide therapy is considered as a highly effective treatment in such applications due to the shorter range and exquisite cytotoxicity of α-particles as compared with β-particles. 213Bi is considered an α-emitter with high clinical potential, due to its short half-life (45.6 minutes) being well matched for use in peptide-receptor radionuclide α-therapy; however, there is limited knowledge available within this context of use. In this study, two novel 213Bi-labeled peptides, DOTA-PEG4-bombesin (DOTA-PESIN) and DO3A-CH2CO-8-aminooctanoyl-Q-W-A-V-G-H-L-M-NH2 (AMBA), were compared with 177Lu (β-emitter)-labeled DOTA-PESIN in a human androgen-independent prostate carcinoma xenograft model (PC-3 tumor). Animals were injected with 177Lu-DOTA-PESIN, 213Bi-DOTA-PESIN, or 213Bi-AMBA to determine the maximum tolerated dose (MTD), biodistribution, and dosimetry of each agent; controls were left untreated or were given nonradioactive 175Lu-DOTA-PESIN. The MTD of 213Bi-DOTA-PESIN and 213Bi-AMBA was 25 MBq (0.68 mCi) whereas 177Lu-DOTA-PESIN showed an MTD of 112 MBq (3 mCi). At these dose levels, 213Bi-DOTA-PESIN and 213Bi-AMBA were significantly more effective than 177Lu-DOTA-PESIN. At the same time, 177Lu-DOTA-PESIN showed minimal, 213Bi-DOTA-PESIN slight, and 213Bi-AMBA marked kidney damage 20 to 30 weeks posttreatment. These preclinical data indicate that α-therapy with 213Bi-DOTA-PESIN or 213Bi-AMBA is more efficacious than β-therapy. Furthermore, 213Bi-DOTA-PESIN has a better safety profile than 213Bi-AMBA, and represents a possible new approach for use in peptide-receptor radionuclide α-therapy treating recurrent prostate cancer. Cancer Res; 71(3); 1009–18. ©2011 AACR.
Deoxycytidine Kinase Modulates the Impact of the ABC Transporter ABCG2 on Clofarabine Cytotoxicity
Authors: Nagai Shinjiro , Takenaka Kazumasa , Nachagari Deepa , Rose Charles , Domoney Kali , Sun Daxi , Sparreboom Alex , Schuetz John D. 
Published: January 2011

Abstract
Purine nucleoside antimetabolites, such as clofarabine, are effective antileukemic agents. However, their effectiveness depends on an initial activation step in which they are monophosphorylated by deoxycytidine kinase (dCK). Some purine nucleoside antimetabolites and their monophosphate derivatives are exported by the ABC transporter ABCG2. Because clofarabine is a dCK substrate, and we show substantial variation in dCK and ABCG2 in myeloid leukemia, we hypothesized that the activity of dCK may modulate ABCG2-mediated resistance to clofarabine by regulating the formation of clofarabine monophosphate. We show that ABCG2 influence on clofarabine cytotoxicity was markedly influenced by dCK activity. When dCK expression was reduced by siRNA, clofarabine cytotoxicity was strongly reduced by enhanced ABCG2-mediated efflux. Conversely, dCK overexpression blunted ABCG2-mediated efflux of clofarabine by increasing the formation of clofarabine nucleotides. The use of an ABCG2 inhibitor confirmed that ABCG2 export of clofarabine is maximal when dCK levels are minimal. Analysis of intracellular clofarabine metabolites suggested that ABCG2 exported clofarabine more readily than clofarabine monophosphate. That ABCG2 primarily effluxes clofarabine, but not chlorfarabine-monophosphate, was confirmed by HPLC analysis of drug exported from ABCG2-overexpressing cells. Because the level and function of dCK and ABCG2 vary substantially among other types of cancer, these findings have important implications not only for clofarabine therapy but for purine nucleoside therapy in general. Therefore, we propose that addition of ABCG2 inhibitors would effectively increase the antitumor efficacy of purine nucleosides by blocking drug efflux that may be a significant mode of resistance when dCK levels are low. Cancer Res; 71(5); 1781–91. ©2011 AACR.
Dual IGF-I/II–Neutralizing Antibody MEDI-573 Potently Inhibits IGF Signaling and Tumor Growth
Authors: Gao Jin , Chesebrough Jon W. , Cartlidge Susan A. , Ricketts Sally-Ann , Incognito Leonard , Veldman-Jones Margaret , Blakey David C. , Tabrizi Mohammad , Jallal Bahija , Trail Pamela A. , Coats Steven , Bosslet Klaus , Chang Yong S. 
Published: January 2011

Abstract
Insulin-like growth factors (IGF), IGF-I and IGF-II, are small polypeptides involved in regulating cell proliferation, survival, differentiation, and transformation. IGF activities are mediated through binding and activation of IGF-1R or insulin receptor isoform A (IR-A). The role of the IGF-1R pathway in promoting tumor growth and survival is well documented. Overexpression of IGF-II and IR-A is reported in multiple types of cancer and is proposed as a potential mechanism for cancer cells to develop resistance to IGF-1R–targeting therapy. MEDI-573 is a fully human antibody that neutralizes both IGF-I and IGF-II and inhibits IGF signaling through both the IGF-1R and IR-A pathways. Here, we show that MEDI-573 blocks the binding of IGF-I and IGF-II to IGF-1R or IR-A, leading to the inhibition of IGF-induced signaling pathways and cell proliferation. MEDI-573 significantly inhibited the in vivo growth of IGF-I– or IGF-II–driven tumors. Pharmacodynamic analysis demonstrated inhibition of IGF-1R phosphorylation in tumors in mice dosed with MEDI-573, indicating that the antitumor activity is mediated via inhibition of IGF-1R signaling pathways. Finally, MEDI-573 significantly decreased 18F-fluorodeoxyglucose (18F-FDG) uptake in IGF-driven tumor models, highlighting the potential utility of 18F-FDG-PET as a noninvasive pharmacodynamic readout for evaluating the use of MEDI-573 in the clinic. Taken together, these results demonstrate that the inhibition of IGF-I and IGF-II ligands by MEDI-573 results in potent antitumor activity and offers an effective approach to selectively target both the IGF-1R and IR-A signaling pathways. Cancer Res; 71(3); 1029–40. ©2011 AACR.
Prediction and Genetic Demonstration of a Role for Activator E2Fs in Myc-Induced Tumors
Authors: Fujiwara Kenichiro , Yuwanita Inez , Hollern Daniel P. , Andrechek Eran R. 
Published: January 2011

Abstract
Advances in genomic signatures have begun to dissect breast cancer heterogeneity and application of these signatures will allow the prediction of which pathways are important in tumor development. Here we used genomic signatures to predict involvement of specific E2F transcription factors in Myc-induced tumors. We genetically tested this prediction by interbreeding Myc transgenics with mice lacking various activator E2F alleles. Tumor latency decreased in the E2F1 mutant background and significantly increased in both the E2F2 and E2F3 mutants. Investigating the mechanism behind these changes revealed a reduction in apoptosis in the E2F1 knockout strain. E2F2 and E2F3 mutant backgrounds alleviated Myc proliferative effects on the pregnant mammary gland, reducing the susceptible tumor target population. Gene expression data from tumors revealed that the E2F2 knockout background resulted in fewer tumors with EMT, corresponding with a reduction in probability of Ras activation. In human breast cancer we found that a low probability of E2F2 pathway activation was associated with increased relapse-free survival time. Together these data illustrate the predictive utility of genomic signatures in deciphering the heterogeneity within breast cancer and illustrate the unique genetic requirements for individual E2Fs in mediating tumorigenesis in both mouse models and human breast cancer. Cancer Res; 71(5); 1924–32. ©2011 AACR.
GSK1120212 (JTP-74057) Is an Inhibitor of MEK Activity and Activation with Favorable Pharmacokinetic Properties for Sustained In Vivo Pathway Inhibition
Authors: Gilmartin Aidan G. , Bleam Maureen R. , Groy Arthur , Moss Katherine G. , Minthorn Elisabeth A. , Kulkarni Swarupa G. , Rominger Cynthia M. , Erskine Symon , Fisher Kelly E. , Yang Jingsong , Zappacosta Francesca , Annan Roland , Sutton David , Laquerre Sylvie G. 
Published: January 2011

Abstract
Purpose: Despite their preclinical promise, previous MEK inhibitors have shown little benefit for patients. This likely reflects the narrow therapeutic window for MEK inhibitors due to the essential role of the P42/44 MAPK pathway in many nontumor tissues. GSK1120212 is a potent and selective allosteric inhibitor of the MEK1 and MEK2 (MEK1/2) enzymes with promising antitumor activity in a phase I clinical trial (ASCO 2010). Our studies characterize GSK1120212' enzymatic, cellular, and in vivo activities, describing its unusually long circulating half-life.
Experimental Design: Enzymatic studies were conducted to determine GSK1120212 inhibition of recombinant MEK, following or preceding RAF kinase activation. Cellular studies examined GSK1120212 inhibition of ERK1 and 2 phosphorylation (p-ERK1/2) as well as MEK1/2 phosphorylation and activation. Further studies explored the sensitivity of cancer cell lines, and drug pharmacokinetics and efficacy in multiple tumor xenograft models.
Results: In enzymatic and cellular studies, GSK1120212 inhibits MEK1/2 kinase activity and prevents Raf-dependent MEK phosphorylation (S217 for MEK1), producing prolonged p-ERK1/2 inhibition. Potent cell growth inhibition was evident in most tumor lines with mutant BRAF or Ras. In xenografted tumor models, GSK1120212 orally dosed once daily had a long circulating half-life and sustained suppression of p-ERK1/2 for more than 24 hours; GSK1120212 also reduced tumor Ki67, increased p27Kip1/CDKN1B, and caused tumor growth inhibition in multiple tumor models. The largest antitumor effect was among tumors harboring mutant BRAF or Ras.
Conclusions: GSK1120212 combines high potency, selectivity, and long circulating half-life, offering promise for successfully targeting the narrow therapeutic window anticipated for clinical MEK inhibitors. Clin Cancer Res; 17(5); 989–1000. ©2011 AACR.
An Antibody–Drug Conjugate Targeting the Endothelin B Receptor for the Treatment of Melanoma
Authors: Asundi Jyoti , Reed Chae , Arca Jennifer , McCutcheon Krista , Ferrando Ronald , Clark Suzanna , Luis Elizabeth , Tien Janet , Firestein Ron , Polakis Paul 
Published: January 2011

Abstract
Purpose: To identify and evaluate targets amenable to antibody therapy in melanoma.
Experimental Design: We searched for mRNA transcripts coding for cell-surface proteins with expression patterns similar to that of the melanoma oncogene MITF. One such candidate, the endothelin B receptor (EDNBR), was first analyzed for a functional contribution to tumor growth by conditional induction of shRNA. Second, antibodies were raised to the receptor, conjugated with monomethyl auristatin E, and tested for efficacy against melanoma tumor models generated from cell lines.
Results: Conditional knockdown of the receptor in tumor xenograft models resulted in only a modest impact on tumor growth. A monoclonal antibody reactive with the N-terminal tail of EDNBR was found to internalize rapidly into melanoma cells. When conjugated with monomethyl auristatin E, the antibody–drug conjugate (ADC) showed remarkable efficacy against human melanoma cell lines and xenograft tumor models that was commensurate with levels of receptor expression. Comparative immunohistochemistry revealed a range of EDNBR expression across a panel of human melanomas, with the majority expressing levels equivalent to or greater than that in the models responsive to the ADC.
Conclusion: An ADC targeting the EDNBR is highly efficacious in preclinical models of melanoma. Clin Cancer Res; 17(5); 965–75. ©2011 AACR.
Human-Sled Dog Relations: What Can We Learn from the Stories and Experiences of Mushers?
Authors: Kuhl Gail 
Published: January 2011

AbstractIn this qualitative study, the elements and quality of musher-sled dog relationships were investigated. In-depth interviews with a narrative design were conducted with eight mushers from northern Minnesota and northwestern Ontario. The mushers were asked to contribute ideas by sharing stories and experiences of working with dogs, as well as art or photographs. While all the participants had their own ideas about musher-sled dog relationships, six themes emerged. The mushers stated the importance of getting to know the dogs, their respect for their sled dogs’ abilities, the idea of a two-way communication that takes place, the importance of trust, the notion of partnership, and what can be learned through working with sled dogs. This study supports other research suggesting that humans and animals engage in interspecies relationships and that these can be quality relationships with multiple elements. The importance of researching and teaching about dogs as subjects is discussed, as well as the significance of humans having direct experience with other animals.
Cruel Intimacies and Risky Relationships: Accounting for Suffering in Industrial Livestock Production
Authors: Purcell Natalie 
Published: January 2011

AbstractThis article investigates the hypothesis that greater human-livestock intimacy can deter cruelty and mitigate suffering in the industrial production of animals for human consumption. The history of industrial agriculture in North America is one of increasingly utilitarian, profit-based, and technologically mediated relationships between humans and the animals they raise and kill for food. Under what circumstances is the physical and emotional distance between producers, consumers, and consumed animals an impetus toward uncaring and irresponsible relationships? Do even intimate interspecies encounters in livestock production involve cruelty and suffering? This article addresses these questions and evaluates reform options by attending to both the localized arrangements and systemic structures of industrial livestock production. Finally, it proposes a risk-mapping strategy to assess the plausibility of caring intimacies in livestock production.