bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of the written request process on drug development in childhood cancer
Authors: Snyder Kristen M. , Reaman Gregory , Avant Debbie , Pazdur Richard 
Published: January 2013

AbstractPurposeThe Food and Drug Administration (FDA) Modernization Act, enacted in 1997, created a pediatric exclusivity incentive allowing sponsors to qualify for an additional 6 months of marketing exclusivity after satisfying the requirements outlined in the Written Request (WR). This review evaluates the impact of the WR mechanism on the development of oncology drugs in children.MethodsA search of the FDA document archiving, reporting, and regulatory tracking system was performed for January 1, 2000 to December 31, 2010. Drugs were identified and pediatric‐specific labeling information was obtained from Drugs@fda.gov and FDA Pediatric Labeling Changes Table.ResultsFifty WRs have been issued for oncology drugs. Pediatric studies have been submitted for 14 drugs. Thirteen received pediatric exclusivity. As of December 31, 2010, labeling changes have been made for 11 drugs. Three drugs were approved for pediatric use.ConclusionWRs have provided a mechanism to promote the study of drugs in pediatric malignancies. Information from studies resulting from the WRs regarding safety, pharmacokinetics, and tolerability of oncology drugs has been incorporated into pediatric labeling for 11/14 of the drugs. Earlier communication and collaboration between the FDA, National Cancer Institute, clinical investigators, and commercial sponsors are envisioned to facilitate the identification and prioritization of emerging new drugs of interest for WR consideration. Since this is the only regulatory mechanism, resulting from specific legislative initiatives relevant to cancer drug development for children, efforts to enhance its impact on increasing drug approval for pediatric cancer indications are warranted. Pediatr Blood Cancer 2013; 60: 531–537. © 2013 Wiley Periodicals, Inc.
Factors associated with poor quality of life in survivors of childhood acute lymphoblastic leukemia and lymphoma
Authors: Kanellopoulos Adriani , Hamre Hanne Mari , Dahl Alv A. , Fosså Sophie D. , Ruud Ellen 
Published: January 2013

AbstractBackgroundPrevious studies of health‐related quality of life (QoL) in childhood cancer survivors have hardly focused on factors associated with poor QoL. The aims of our study were: (1) to assess QoL in long‐term survivors (LTSs) of childhood acute lymphoblastic leukemia (ALL) and lymphomas compared to age‐matched controls from the general population (NORMs). (2) To investigate factors associated with poor QoL in LTSs.ProcedureThis population‐based cross‐sectional study enrolled 285 LTSs of ALL and lymphomas diagnosed between 1970 and 2002 at age <18 years. The LTSs completed an extensive mailed questionnaire including the Short Form 36 (SF‐36) as QoL‐measure. NORMs consisted of five age‐matched controls for each LTS (N = 1,425). Poor QoL was defined as SF‐36 physical or mental component summary score <40.ResultsThe median age of LTSs' at survey was 30 years (range: 18–54), median follow‐up time 21 years (range: 7–39). Compared to NORMs, LTSs scored significantly lower on 7 of 8 SF‐36 subscales. Among LTSs 32% reported poor QoL versus 19% among NORMs (P < 0.001). Among LTSs, psychosocial, lifestyle‐ and health‐related variables, but not type of malignancy, treatment factors or socio‐demographic factors were clinically significantly associated with poor QoL in bivariate regression analyses. In multivariate analysis, levels of fatigue, anxiety and depression, as well as obesity and insomnia remained significantly associated with poor QoL.ConclusionSignificantly more LTSs than age‐matched NORMs experienced poor QoL. Clinically significant associations with fatigue, anxiety, depression, obesity and insomnia were observed, which may be amenable for interventions, and thereby improvement of QoL in LTSs. Pediatr Blood Cancer 2013; 60: 849–855. © 2013 Wiley Periodicals, Inc.
Phase I/II trial of clofarabine and cytarabine in children with relapsed/refractory acute lymphoblastic leukemia (AAML0523): A report from the Children's Oncology Group
Authors: Cooper Todd M. , Razzouk Bassem I. , Gerbing Robert , Alonzo Todd A. , Adlard Kathleen , Raetz Elizabeth , Gamis Alan S. , Perentesis John , Whitlock James A. 
Published: January 2013

AbstractBackgroundThe discovery of effective re‐induction regimens for children with more than one relapse of acute lymphoblastic leukemia (ALL) remains elusive. The novel nucleoside analog clofarabine exhibits modest single agent efficacy in relapsed ALL, though optimal combinations of this agent with other active chemotherapy drugs have not yet been defined. Herein we report the response rates of relapsed ALL patients treated on Children's Oncology Group study AAML0523, a Phase I/II study of the combination of clofarabine and cytarabine.ProcedureAAML0523 enrolled 21 children with ALL in second or third relapse, or those refractory to re‐induction therapy. The study consisted of two phases: a dose finding phase and an efficacy phase. The dose finding portion consisted of a single dose escalation/de‐escalation of clofarabine for 5 days in combination with a fixed dose of cytarabine (1 g/m2/day for 5 days). Eight patients received clofarabine at 40 mg/m2/day and 13 patients at 52 mg/m2/day.ResultsToxicities observed at all doses of clofarabine were typical of intensive chemotherapy regimens for leukemia, with infection being the most common. We did not observe significant hepatotoxicity as reported in other clofarabine combination regimens. The recommended pediatric Phase II dose of clofarabine in combination with cytarabine for the efficacy portion of AAML0523 was 52 mg/m2. Of 21 patients with ALL, 3 (14%) achieved a complete response (CR). Based on the two‐stage design definition of first‐stage inactivity, the therapy was deemed ineffective.ConclusionThe combination of clofarabine and cytarabine in relapsed/refractory childhood ALL does not warrant further clinical investigation. Pediatr Blood Cancer 2013; 60: 1141–1147. © 2013 Wiley Periodicals, Inc.
Utility of platelet function analyzer as a screening tool for the diagnosis of Von Willebrand disease in adolescents with menorrhagia
Authors: Naik Swati , Teruya Jun , Dietrich Jennifer E. , Jariwala Purvi , Soundar Esther , Venkateswaran Lakshmi 
Published: January 2013

AbstractBackgroundVon Willebrand disease (VWD), and in particular, VWD type 1 and low VW factor (defined as Von Willebrand Ristocetin cofactor activity (RCoF) <30 and <50 IU/dl, respectively with normal multimers) are frequently detected in adolescents with menorrhagia and both groups benefit from similar management. Platelet function analyzer (PFA‐100®) is often used as a screening test to detect VWD. We analyzed the utility of PFA‐100® as a screening tool in the detection of VWD type 1 and low VW factor (VWF) in an exclusive adolescent population with menorrhagia.MethodsThe study population consisted of adolescents with menorrhagia who had simultaneously drawn blood samples for VWD and PFA‐100®. Abnormal PFA‐100® was defined as values >183 seconds for collagen/epinephrine and/or >126 seconds for collagen/ADP.ResultsOf a total of 235 patients tested, 23 patients had RCoF <50 IU/dl and normal multimer patterns. Statistical analysis of the utility of PFA‐100® in detecting RCoF <50 IU/dl with normal multimers yielded sensitivity, specificity, positive predictive, and negative predictive values of 52%, 89%, 34%, and 95%, respectively.ConclusionsBased on our results, PFA‐100® was not sufficiently sensitive to detect RCoF values <50 IU/dl with normal multimer patterns in teen‐aged women with menorrhagia. We conclude that in the setting of adolescent menorrhagia, PFA‐100® does not have utility as an initial screening test for the diagnosis of VWD and in particular, low VWF and that clinicians need to be aware of this limitation of PFA‐100® while evaluating adolescents with menorrhagia. Pediatr Blood Cancer 2013; 60: 1184–1187. © 2013 Wiley Periodicals, Inc.
SIOP‐PODC recommendations for graduated‐intensity treatment of retinoblastoma in developing countries
Authors: Chantada Guillermo , Luna‐Fineman Sandra , Sitorus Rita S. , Kruger Mariana , Israels Trijn , Leal‐Leal Carlos , Bakhshi Sameer , Qaddoumi Ibrahim , Abramson David H. , Doz François ,   SIOP‐PODC graduated‐intensity retinoblastoma guidelines writing committee
Published: January 2013

AbstractRetinoblastoma remains incurable in many regions of the world. The major obstacles to cure are delayed diagnosis, poor treatment compliance, and lack of evidence‐based recommendations for clinical management. Although enucleation is curative for intraocular disease, in developing countries retinoblastoma is often diagnosed after the disease has disseminated beyond the eye. A SIOP‐PODC committee generated guidelines for the clinical management of retinoblastoma in developing countries and developed a classification system based on the resources available in those settings. Recommendations are provided for staging and treatment of unilateral and bilateral retinoblastoma and counseling of families for whom compliance is an issue. Pediatr Blood Cancer 2013; 60: 719–727. © 2013 Wiley Periodicals, Inc.
Sequential administration of methotrexate and asparaginase in relapsed or refractory pediatric acute myeloid leukemia
Authors: Buaboonnam Jassada , Cao Xueyuan , Pauley Jennifer L. , Pui Ching‐Hon , Ribeiro Raul C. , Rubnitz Jeffrey E. , Inaba Hiroto 
Published: January 2013

AbstractBackgroundThe efficacy of combination chemotherapy with methotrexate (MTX) and asparaginase is not well known in relapsed and refractory acute leukemia after contemporary therapy.ProcedureA retrospective study of pediatric patients with relapsed or refractory acute myeloid leukemia (AML) who received MTX and asparaginase as a salvage therapy at St. Jude Children Research Hospital was performed. MTX was given intravenously followed by a dose of asparaginase intramuscularly or intravenously 24 hours later. The chemotherapy cycle was repeated every 7–10 days. Response, survival, and toxicities were evaluated.ResultsFifteen patients, median age 10.5 years (range, 1.1–18.5 years), were treated. Median number of previous therapeutic regimens was three (range, 1–4). Six patients responded to treatment (three had morphologic complete remission with incomplete blood count recovery, two had partial remission, and one had stable disease for 16 months), and four are still alive. Three of six responders had monoblastic leukemia, and also developed tumor lysis syndrome. The 1‐ and 2‐year overall survival rates are 35.6% and 17.8%, respectively. The most common adverse event was transient elevation of transaminases (nine patients). Two patients developed pancreatitis. Episodes of febrile neutropenia were rare (two patients), and most courses (75 out of 93 total courses) were given in an outpatient setting.ConclusionsCombination chemotherapy with MTX and asparaginase appears to be an effective salvage therapy and well tolerated in patients with relapsed or refractory childhood AML, even in those heavily pretreated with contemporary frontline or salvage therapy. Pediatr Blood Cancer 2013; 60: 1161–1164. © 2013 Wiley Periodicals, Inc.
Characterization of osteoblastic and osteolytic proteins in prostate cancer bone metastases
Authors: Larson Sandy R. , Zhang Xiaotun , Dumpit Ruth , Coleman Ilsa , Lakely Bryce , Roudier Martine , Higano Celestia S. , True Lawrence D. , Lange Paul H. , Montgomery Bruce , Corey Eva , Nelson Peter S. , Vessella Robert L. , Morrissey Colm 
Published: January 2013

AbstractBACKGROUNDApproximately 90% of patients who die of Prostate Cancer (PCa) have bone metastases, which promote a spectrum of osteoblastic, osteolytic or mixed bone responses. Numerous secreted proteins have been reported to promote osteoblastic or osteolytic bone responses. We determined whether previously identified and/or novel proteins were associated with the osteoblastic or osteolytic response in clinical specimens of PCa bone metastases.METHODSGene expression was analyzed on 14 PCa metastases from 11 patients by microarray profiling and qRT‐PCR, and protein expression was analyzed on 33 PCa metastases from 30 patients by immunohistochemistry on highly osteoblastic and highly osteolytic bone specimens.RESULTSTranscript and protein levels of BMP‐2, BMP‐7, DKK‐1, ET‐1, and Sclerostin were not significantly different between osteoblastic and osteolytic metastases. However, levels of OPG, PGK1, and Substance P proteins were increased in osteoblastic samples. In addition, Emu1, MMP‐12, and sFRP‐1 were proteins identified with a novel role of being associated with either the osteoblastic or osteolytic bone response.CONCLUSIONSThis is the first detailed analysis of bone remodeling proteins in human specimens of PCa bone metastases. Three proteins not previously shown to be involved may have a role in the PCa bone response. Furthermore, our data suggests that the relative expression of numerous, rather than a single, bone remodeling proteins determine the bone response in PCa bone metastases. Prostate 73: 932–940, 2013. © 2013 Wiley Periodicals, Inc.
Circular dichroism in angle‐resolved photoemission spectroscopy of topological insulators
Authors: Wang Yihua , Gedik Nuh 
Published: January 2013

Abstractmagnified imageTopological insulators are a new phase of matter that exhibits exotic surface electronic properties. Determining the spin texture of this class of material is of paramount importance for both fundamental understanding of its topological order and future spin‐based applications. In this article, we review the recent experimental and theoretical studies on the differential coupling of left‐circularly versus right‐circularly polarized light to the topological surface states in angle‐resolved photoemission spectroscopy. These studies have shown that the polarization of light and the experimental geometry play a veryimportant role in both photocurrent intensity and spin polarization of photoelectrons emitted from the topological surface states. A general photoemission matrix element calculation can quantitatively explain the observations and is also applicable to topologically trivial systems with strong spin–orbit coupling. These experimental and theoretical investigations suggest that optical excitation with circularly polarized light is a promising route towards mapping the spin–orbit texture and manipulating the spin orientation in topological and other spin–orbit coupled materials.magnified imageThe circular‐dichroic angle‐resolved photoemission spectrum of Bi2Se3 as obtained by the difference between spectra taken with left‐circularly vs. right‐circularly polarized light using a time‐of‐flight electron spectrometer.(© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Ensemble prediction of coastal flood risk arising from overtopping by linking meteorological, ocean, coastal and surf zone models
Authors: Zou Qing‐Ping , Chen Yongping , Cluckie Ian , Hewston Richard , Pan Shunqi , Peng Zhong , Reeve Dominic 
Published: January 2013

AbstractThis paper presents an integrated ‘Clouds‐to‐Coast’ ensemble modelling framework of coastal flood risk due to wave overtopping. The modelling framework consists of four key components: meteorological forecasts, wave–tide–surge predictions, nearshore wave models and surf zone models. This type of ensemble prediction approach allows us to estimate the probabilities of various outcomes and so improve our understanding of the reliability of results. It also provides a measure of the uncertainty associated with predictions, which can be particularly large for extreme storms, and allows us to assess how the uncertainty propagates from meteorological forecasts to overtopping and subsequent coastal flood risk predictions. Copyright © 2013 Royal Meteorological Society
Assimilation of GNSS ZTD and radar radial velocity for the benefit of very‐short‐range regional weather forecasts
Authors: de Haan S. 
Published: January 2013

AbstractWind, humidity and temperature observations from aircraft and radiosondes are generally used to find the best initial state of the atmosphere for numerical weather prediction (NWP). To be of use for very‐short‐range numerical weather forecasting (or numerical nowcasting), these observations need to be available within several minutes after observation time. Radiosondes have a typically observation latency of over 30 min and arrive too late for numerical nowcasting. Zenith Total Delay (ZTD) observations obtained from a ground‐based network of Global Navigation Satellite System (GNSS) receivers can fill this gap of lacking rapid humidity information. ZTD contains information on the total amount of water vapour. Other rapidly available observations, such as radial wind estimates from Doppler weather radars, can also be exploited. Both observations are available with a delay of less than 5 min with adequate spatial resolution. In this article, the impact of assimilation of these humidity and wind observations in a very‐short‐range regional forecast model is assessed over a four‐month summer period and a six‐week winter period. As a reference for the impact, GNSS observations are also assimilated in a three‐hourly NWP scheme with longer observation cut‐off times. The quality of the forecasts is evaluated against radiosonde observations, radar radial wind and hourly precipitation observations. Assimilation of both GNSS ZTD and radar radial winds resulted in a positive impact on humidity, rainfall and wind forecasts.
Steady and unsteady nonlinear internal waves incident on an interface
Authors: Grimshaw Roger , McHugh John 
Published: January 2013

AbstractSteady nonlinear internal waves are commonly described by the Dubreil‐Jacotin–Long equation. This equation contains unknown functions of the stream function, representing the density and vorticity fields. Often these are determined by upstream conditions where the flow is assumed to be known. But for the case when the waves are periodic in the horizontal direction, these functions need to be determined instead by consideration of the source of the waves, and in particular by the wave‐induced mean flow. Here we show that this situation is particularly important for waves incident and reflected from an interface, representing a sharp change in the background density stratification, such as that at the tropopause. The combination of the incident and reflected wave‐induced mean flows generates a sharp shear near the interface.
Surface‐enhanced Raman scattering imaging using noble metal nanoparticles
Authors: Wilson Andrew J. , Willets Katherine A. 
Published: January 2013

AbstractSurface‐enhanced Raman scattering (SERS) imaging is a powerful technique for studying biological systems both in vitro and in vivo. In SERS, Raman scattering from molecules located near the surface of either gold or silver nanoparticles is enhanced by 105–108. This review describes the basic enhancement mechanism of SERS and provides experimental details that must be considered when performing a SERS imaging experiment with a focus on cellular imaging. Specific examples highlighting the power of SERS for measuring chemical distributions in cells, signal multiplexing, and following dynamic motion of SERS probes in vivo are provided. Potential future directions in which SERS is combined with super‐resolution imaging are also described. WIREs Nanomed Nanobiotechnol 2013, 5:180–189. doi: 10.1002/wnan.1208This article is categorized under:

Diagnostic Tools > Diagnostic Nanodevices
Diagnostic Tools > In Vitro Nanoparticle-Based Sensing
Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Dark Matter in a twisted bottle
Authors: Arbey Alexandre , Cacciapaglia Giacomo , Deandrea Aldo , Kubik Bogna 
Published: January 2013

Abstract

The real projective plane is a compact, non-orientable orbifold of Euler characteristic 1 without boundaries, which can be described as a twisted Klein bottle. We shortly review the motivations for choosing such a geometry among all possible two-dimensional orbifolds, while the main part of the study will be devoted to dark matter study and limits in Universal Extra Dimensional (UED) models based on this peculiar geometry. In the following we consider such a UED construction based on the direct product of the real projective plane with the standard four-dimensional Minkowski space-time and discuss its relevance as a model of a weakly interacting Dark Matter candidate.
One important difference with other typical UED models is the origin of the symmetry leading to the stability of the dark matter particle. This symmetry in our case is a remnant of the six-dimensional Minkowski space-time symmetry partially broken by the compactification. Another important difference is the very small mass splitting between the particles of a given Kaluza-Klein tier, which gives a very important role to co-annihilation effects. Finally the role of higher Kaluza-Klein tiers is also important and is discussed together with a detailed numerical description of the influence of the resonances.
2:1 for naturalness at the LHC?
Authors: Arkani-Hamed Nima , Blum Kfir , D’Agnolo Raffaele Tito , Fan JiJi 
Published: January 2013

Abstract

A large enhancement of a factor of 1.5 - 2 in Higgs production and decay in the diphoton channel, with little deviation in the ZZ channel, can only plausibly arise from a loop of new charged particles with large couplings to the Higgs. We show that, allowing only new fermions with marginal interactions at the weak scale, the required Yukawa couplings for a factor of 2 enhancement are so large that the Higgs quartic coupling is pushed to large negative values in the UV, triggering an unacceptable vacuum instability far beneath the 10 TeV scale. An enhancement by a factor of 1.5 can be accommodated if the charged particles are lighter than 150 GeV, within reach of discovery in almost all cases in the 8 TeV run at the LHC, and in even the most difficult cases at 14 TeV. Thus if the diphoton enhancement survives further scrutiny, and no charged particles beneath 150 GeV are found, there must be new bosons far beneath the 10 TeV scale. This would unambiguously rule out a large class of fine-tuned theories for physics beyond the Standard Model, including split SUSY and many of its variants, and provide strong circumstantial evidence for a natural theory of electroweak symmetry breaking at the TeV scale. Alternately, theories with only a single fine-tuned Higgs and new fermions at the weak scale, with no additional scalars or gauge bosons up to a cutoff much larger than the 10 TeV scale, unambiguously predict that the hints for a large diphoton enhancement in the current data will disappear.
Tinnitus and Patterns of Hearing Loss
Authors: Tan Christine M. , Lecluyse Wendy , McFerran Don , Meddis Ray 
Published: January 2013

Abstract
Tinnitus is strongly linked with the presence of damaged hearing. However, it is not known why tinnitus afflicts only some, and not all, hearing-impaired listeners. One possibility is that tinnitus patients have specific inner ear damage that triggers tinnitus. In this study, differences in cochlear function inferred from psychophysical measures were measured between hearing-impaired listeners with tinnitus and hearing-impaired listeners without tinnitus. Despite having similar average hearing loss, tinnitus patients were observed to have better frequency selectivity and compression than those without tinnitus. The results suggest that the presence of subjective tinnitus may not be strongly associated to outer hair cell impairment, at least where hearing impairment is evident. The results also show a different average pattern of hearing impairment amongst the tinnitus patients, consistent with the suggestion that inner hair cell dysfunction with subsequent reduced auditory innervation is a possible trigger of tinnitus.