bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bayesian clinical trials at the University of Texas M. D. Anderson Cancer Center
Authors: Biswas Swati , Liu Diane D , Lee J Jack , Berry Donald A 
Published: June 2009

Background The Bayesian approach is being used increasingly in medical research. In particular, it has become a standard in designing clinical trials at the University of Texas M. D. Anderson Cancer Center. Purpose/Methods To address the extent and nature of Bayesian trials conducted at M. D. Anderson, we reviewed the protocols registered in the Protocol Document Online System between 2000 and early 2005. We summarize our findings and give details for three innovative trials that typify those in which a Bayesian approach has played a major role at the center. Results Of 964 protocols reviewed, 59% were conducted solely at M. D. Anderson and the rest were multicenter trials. Bayesian designs and analyses were used in about 20% (195/964) of the protocols that we reviewed. Of the 520 protocols identified as phase I or II drug trials, about 34% were Bayesian. Most of the 195 Bayesian trials were designed by M. D. Anderson statisticians. The Bayesian design features most commonly used were the continuous reassessment method in phase I (toxicity) trials, adaptive randomization in phase II trials, and designs to monitor efficacy and toxicity simultaneously. We also provide an insider's view regarding some practical considerations that have made the design and implementation of so many Bayesian trials possible. Limitations We reviewed only a subset of all M. D. Anderson protocols, but did not exclude any available in electronic form. Conclusions The large number of Bayesian trials conducted at M. D. Anderson testifies to the receptivity to the Bayesian approach within the center, including principal investigators, regulatory review committees, and patients. Statisticians who take a Bayesian perspective can successfully work to establish a culture of innovation in clinical trial design.
Bayesian Design of Single-arm Phase II Clinical Trials with Continuous Monitoring
Authors: Johnson Valen E , Cook John D 
Published: June 2009

Background Bayesian designs are increasingly used to conduct phase II clinical trials. However, stopping boundaries in most Bayesian designs are defined from posterior credible intervals. The use of designs based on posterior credible intervals results in a loss of efficiency when compared to formal stopping rules based on Bayesian hypothesis tests. Such designs also introduce an unnecessary element of subjectivity in the interpretation of trial results. Methods We derive a new class of Bayesian designs based on formal hypothesis tests. The prior densities used to define the alternative hypotheses in these tests assign no mass to parameter values that are consistent with the null hypotheses and are called nonlocal alternative prior densities. Results We show that Bayesian designs based on hypothesis tests and nonlocal alternative prior densities are more efficient than common Bayesian designs based on posterior credible intervals and common frequentist designs. In contrast to trial designs based on Bayesian credible intervals, we demonstrate that the mis-specification of the prior densities used to describe the anticipated effect of the experimental treatment in designs based on hypothesis tests cannot increase the expected weight of evidence in favor of the trial agent. Limitations Extension of test-based designs to phase I—II designs and randomized phase II designs remains an open research question. Conclusions Phase II single-arm trials designed using Bayesian hypothesis tests with nonlocal alternatives provide better operating characteristics, use fewer patients per correct decision, and provide more directly interpretable results than other commonly used Bayesian and frequentist designs. Because the mis-specification of the prior density on the effect of the experimental agent decreases the expected weight of evidence that is collected in favor of the experimental treatment, the use of Bayesian hypothesis tests to design clinical trials also eliminates a potential source of bias often associated with trials designed using posterior credible intervals.
Scientific and political challenges in North America's first randomized controlled trial of heroin-assisted treatment for severe heroin addiction: Rationale and design of the NAOMI study
Authors: Oviedo-Joekes Eugenia , Nosyk Bohdan , Marsh David C , Guh Daphne , Brissette Suzanne , Gartry Candice , Krausz Michael , Anis Aslam , Schechter Martin T 
Published: June 2009

Background Heroin addiction is a chronic relapsing disease, best treated with opioid-agonist substitution therapy such as methadone maintenance. However, a subset of the most severely affected individuals do not benefit sufficiently from this treatment. The North American Opiate Medication Initiative (NAOMI) is a randomized clinical trial (RCT) to evaluate the hypothesis that pharmaceutical-grade heroin, diacetylmorphine (DAM) is more effective in retaining patients and improving their outcomes than Methadone Maintenance Treatment (MMT) among those with chronic, refractory injection opioid dependence. Purpose/Methods The study aimed at randomizing 253 participants to two intervention arms: (1) MMT alone or (2) injectable opioids (DAM or hydromorphone) plus adjunctive MMT if deemed appropriate. The planned study duration was 3 years, with a 1-year intake period, 1 year of treatment, and an additional year of follow-up. The NAOMI trial was initiated in March 2005 at two Canadian sites (Vancouver and Montreal). This was the first multicenter RCT in North America to compare the relative efficacy of these different therapeutic strategies. We discuss the rationale behind the NAOMI study design, as well as the scientific and political issues and methodological challenges arising from the conduct of a trial that involves the prescription of a controlled substance to individuals with dependence on that substance. Limitations Restrictive entry criteria led to the exclusion of many otherwise eligible participants, slowing recruitment into the study. Inability to offer DAM treatment beyond 12 months led to artificial boundary effects in the trial. Conclusions Addiction treatment research navigates between science and politics, and evidence-based medicine is many times confronted by moral beliefs. Political considerations influence study design to a further degree than in RCTs treating less-stigmatized disorders with more-reputable medications.
Design, conduct, and analyses of Breast International Group (BIG) 1-98: A randomized, double-blind, phase-III study comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with receptor-positive, early breast cancer
Authors: Giobbie-Hurder Anita , Price Karen N , Gelber Richard D 
Published: June 2009

Background Aromatase inhibitors provide superior disease control when compared with tamoxifen as adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer. Purpose To present the design, history, and analytic challenges of the Breast International Group (BIG) 1-98 trial: an international, multicenter, randomized, double-blind, phase-III study comparing the aromatase inhibitor letrozole with tamoxifen in this clinical setting. Methods From 1998—2003, BIG 1-98 enrolled 8028 women to receive monotherapy with either tamoxifen or letrozole for 5 years, or sequential therapy of 2 years of one agent followed by 3 years of the other. Randomization to one of four treatment groups permitted two complementary analyses to be conducted several years apart. The first, reported in 2005, provided a head-to-head comparison of letrozole versus tamoxifen. Statistical power was increased by an enriched design, which included patients who were assigned sequential treatments until the time of the treatment switch. The second, reported in late 2008, used a conditional landmark approach to test the hypothesis that switching endocrine agents at approximately 2 years from randomization for patients who are disease-free is superior to continuing with the original agent. Results The 2005 analysis showed the superiority of letrozole compared with tamoxifen. The patients who were assigned tamoxifen alone were unblinded and offered the opportunity to switch to letrozole. Results from other trials increased the clinical relevance about whether or not to start treatment with letrozole or tamoxifen, and analysis plans were expanded to evaluate sequential versus single-agent strategies from randomization. Limitations Due to the unblinding of patients assigned tamoxifen alone, analysis of updated data will require ascertainment of the influence of selective crossover from tamoxifen to letrozole. Conclusions BIG 1-98 is an example of an enriched design, involving complementary analyses addressing different questions several years apart, and subject to evolving analytic plans influenced by new data that emerge over time.
The HBS1L-MYB intergenic interval associated with elevated HbF levels shows characteristics of a distal regulatory region in erythroid cells
Authors: Wahlberg Karin , Jiang Jie , Rooks Helen , Jawaid Kiran , Matsuda Fumihiko , Yamaguchi Masao , Lathrop Mark , Thein Swee Lay , Best Steve 
Published: June 2009

Abstract
HBS1L-MYB intergenic polymorphism (HMIP) on chromosome 6q23 is associated with elevated fetal hemoglobin levels and has pleiotropic effects on several hematologic parameters. To investigate potential regulatory activity in the region, we have measured sensitivity of the sequences to DNase I cleavage that identified 3 tissue-specific DNase I hypersensitive sites in the core intergenic interval. Chromatin immunoprecipitation with microarray (ChIP-chip) analysis showed strong histone acetylation in a defined interval of 65 kb corresponding to the core HBS1L-MYB intergenic region in primary human erythroid cells but not in non–MYB-expressing HeLa cells. ChIP-chip analysis also identified several potential cis-regulatory elements as strong GATA-1 signals that coincided with the DNase I hypersensitive sites present in MYB-expressing erythroid cells. We suggest that HMIP contains regulatory sequences that could be important in hematopoiesis by controlling MYB expression. This study provides the functional link between genetic association of HMIP with control of fetal hemoglobin and other hematologic parameters. We also present a large-scale analysis of histone acetylation as well as RNA polymerase II and GATA-1 interactions on chromosome 6q, and α and β globin gene loci. The data suggest that GATA-1 regulates numerous genes of various functions on chromosome 6q.
Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study
Authors: Balgobind Brian V. , Raimondi Susana C. , Harbott Jochen , Zimmermann Martin , Alonzo Todd A. , Auvrignon Anne , Beverloo H. Berna , Chang Myron , Creutzig Ursula , Dworzak Michael N. , Forestier Erik , Gibson Brenda , Hasle Henrik , Harrison Christine J. , Heerema Nyla A. , Kaspers Gertjan J. L. , Leszl Anna , Litvinko Nathalia , Nigro Luca Lo , Morimoto Akira , Perot Christine , Pieters Rob , Reinhardt Dirk , Rubnitz Jeffrey E. , Smith Franklin O. , Stary Jan , Stasevich Irina , Strehl Sabine , Taga Takashi , Tomizawa Daisuke , Webb David , Zemanova Zuzana , Zwaan C. Michel , van den Heuvel-Eibrink Marry M. 
Published: June 2009

Abstract
Translocations involving chromosome 11q23 frequently occur in pediatric acute myeloid leukemia (AML) and are associated with poor prognosis. In most cases, the MLL gene is involved, and more than 50 translocation partners have been described. Clinical outcome data of the 11q23-rearranged subgroups are scarce because most 11q23 series are too small for meaningful analysis of subgroups, although some studies suggest that patients with t(9;11)(p22;q23) have a more favorable prognosis. We retrospectively collected outcome data of 756 children with 11q23- or MLL-rearranged AML from 11 collaborative groups to identify differences in outcome based on translocation partners. All karyotypes were centrally reviewed before assigning patients to subgroups. The event-free survival of 11q23/MLL-rearranged pediatric AML at 5 years from diagnosis was 44% (± 5%), with large differences across subgroups (11% ± 5% to 92% ± 5%). Multivariate analysis identified the following subgroups as independent prognostic predictors: t(1;11)(q21;q23) (hazard ratio [HR] = 0.1, P = .004); t(6;11)(q27;q23) (HR = 2.2, P < .001); t(10;11)(p12;q23) (HR = 1.5, P = .005); and t(10;11)(p11.2;q23) (HR = 2.5, P = .005). We could not confirm the favorable prognosis of the t(9;11)(p22;q23) subgroup. We identified large differences in outcome within 11q23/MLL-rearranged pediatric AML and novel subgroups based on translocation partners that independently predict clinical outcome. Screening for these translocation partners is needed for accurate treatment stratification at diagnosis.
Electro- and Photoactive Molecular Assemblies of Liquid Crystals and Physical Gels
Authors: Kato Takashi , Tanabe Kana 
Published: June 2009

Abstract
Self-organized structures of liquid crystals and self-assembled fibers have great potential as new functional materials. This article highlights self-organization of π-conjugated molecules, leading to the induction of photonic, electronic, and electrochemical properties.
Fluorescence Sensor for Water Content in Organic Solvents Based on Covalent Immobilization of Benzothioxanthene
Authors: Li Zhi-Zhang , Niu Cheng-Gang , Zeng Guang-Ming , Qin Pin-Zhu 
Published: June 2009

Abstract
A derivative of benzothioxanthene, N-(2-methacryloxyethyl)benzo[k,l]thioxanthene-3,4-dicarboximide (MBTD), was used as a fluorescent indicator for determination of water content in organic solvents. MBTD was photocopolymerization-immobilized on a glass surface. The prepared sensor system possesses relatively long lifetime, short response, and recovering time. The reversibility and reproducibility are also adequate for practical measurement.
Mukaiyama Aldol Reaction Catalyzed by Mesoporous Aluminosilicate
Authors: Ito Suguru , Yamaguchi Hitoshi , Kubota Yoshihiro , Asami Masatoshi 
Published: June 2009

Abstract
In the presence of a mesoporous aluminosilicate Al–MCM-41, aldol reaction of various silyl enol ethers with both aromatic and aliphatic aldehydes proceeded under mild reaction conditions to afford the corresponding O-silylated aldol adducts in high yields. The solid acid catalyst was easily recovered and reusable three times.
Periodic Structure in a Fluorene-based Polymer Prepared by Electrochemical Polymerization
Authors: Kawabata Kohsuke , Goto Hiromasa 
Published: June 2009

Abstract
A conjugated copolymer, poly[2,7-di(2-furyl)fluorene], with periodic dielectric microstructure is prepared by electrochemical polymerization using cholesteric liquid crystal as an electrolyte solution. The polymer film thus prepared displays a labyrinthine fingerprint texture formed by a convexo–concave structure, and exhibits a random diffraction grating function. This anisotropic electrochemical polymerization technique is a novel bottom-up approach for preparing one-dimensional photonic crystals.
A Simple Access to Symmetric Diarylamines via Copper(II)-catalyzed Coupling of Aqueous Ammonia with Arylboronic Acids
Authors: Zhou Changfeng , Chen Fan , Yang Dongpeng , Jia Xiaofei , Zhang Lixue , Cheng Jiang 
Published: June 2009

Abstract
A simple and efficient CuII-catalyzed coupling reaction of arylboronic acids with aqueous ammonia under air is described. The reaction was conducted under atmospheric pressure and no additional ligand was required. Benzoic acid was added to tune the basicity of the reaction system.
Ni0-catalyzed Direct Amination of Anisoles Involving the Cleavage of Carbon–Oxygen Bonds
Authors: Tobisu Mamoru , Shimasaki Toshiaki , Chatani Naoto 
Published: June 2009

Abstract
Ni0-catalyzed cross-coupling of aryl methyl ethers with amines is described. The use of an N-heterocyclic carbene as a ligand and NaOt-Bu as a base promotes the amination of anisole derivatives via the cleavage of normally unreactive aryl carbon–oxygen bonds.
Phenanthroline Derivatives for Electron-transport Layer in Organic Light-emitting Devices
Authors: Li Yan-Jun , Sasabe Hisahiro , Su Shi-Jian , Tanaka Daisaku , Takeda Takashi , Pu Yong-Jin , Kido Junji 
Published: June 2009

Abstract
A series of novel phenanthroline derivatives (Phens) have been synthesized and their application to organic light-emitting devices (OLEDs) as an electron-transport layer was investigated. The OLEDs with a structure of ITO/α-NPD/Alq3/Phen/LiF/Al exhibited remarkable performances and lower operating voltages compared to Alq3-based device, indicating that Phens posses favorable electron-transport properties.
Synthesis of Thermotropic Liquid Crystalline Polyimides with Siloxane Linkages
Authors: Shoji Yu , Higashihara Tomoya , Watanabe Junji , Ueda Mitsuru 
Published: June 2009

Abstract
Thermotropic liquid crystalline (LC) semi-aliphatic polyimides have been developed from 3,3′,4,4′-tetracarboxybiphenyl dianhydride (BPDA) and diamines containing siloxane spacer units. These polyimides exhibited high thermal stability and lower transition temperature compared to the corresponding polyimides containing alkyl or oxyethylene spacer units.
Intracellular Enzyme-responsive Fragmentation of Nonviral Gene Carriers Leads to Polyplex Destabilization and Enhanced Transgene Expression
Authors: Hashimoto Tomoko , Tachibana Yoichi , Nozaki Hisae , Mazda Osam , Niidome Takuro , Murakami Akira , Yamaoka Tetsuji 
Published: June 2009

Abstract
A novel cationic oligopeptide has been developed for bioprocessing-triggered nonviral gene delivery systems. Intracellular fragmentation of the carrier in response to endogenous enzyme, furin, led to destabilized polyplexes and enhanced transgene expression.
Enantioselective Reduction of Aliphatic Ketones Using Oxazaborolidine Catalyst Generated In Situ from Chiral Lactam Alcohol and Phenoxyborane
Authors: Kawanami Yasuhiro , Mikami Yudai , Hoshino Katsuhiro , Suzue Mikiko , Kajihara Izumi 
Published: June 2009

Abstract
Oxazaborolidine catalyst generated in situ from chiral lactam alcohol 3 and p-iodophenoxyborane at room temperature was found to catalyze the enantioselective borane reduction of various prochiral aliphatic ketones at −20 °C with high enantioselectivity up to 98% ee.
Catalytic Cyclization of Alkenyl N,O-Acetals by Fe(OTf)3
Authors: Komeyama Kimihiro , Igawa Ryoichi , Morimoto Takayuki , Takaki Ken 
Published: June 2009

Abstract
Fe(OTf)3, was found to be a good catalyst for the cyclization of alkenyl N,O-acetals to give various nitrogen-containing heterocycles in high yields.
Gender and self‐reported mental health problems: Predictors of help seeking from a general practitioner
Authors: Doherty D. Tedstone , Kartalova‐O'Doherty Y. 
Published: June 2009

ObjectivesFindings have shown that many people do not seek help when experiencing psychological distress. The main aim of this paper is to examine the socio‐demographic and health status factors that predict help seeking for self‐reported mental health problems for males and females from a general practitioner (GP).DesignThe analysis used data from the HRB National Psychological Wellbeing and Distress Survey – a telephone survey of the population aged 18 years and over.MethodsTelephone numbers were selected on a random probability basis. An initial set of random clusters was selected from the Geodirectory. Using these sampling areas, random digit dialling was used to generate a random telephone sample. Data were weighted on key variables. Respondents who reported mental health problems in the previous year were included in the current study (382/2,674).ResultsThe findings showed gender differences in the models of predictors between males and females with more factors influencing attendance at the GP for males than for females. While only social limitations and access to free health care predicted female attendance, a range of socio‐demographic and psychological factors influenced male attendance.ConclusionsFindings suggest that a ‘gender sensitive approach’ should be applied to mental health policies and mental health promotion and prevention programmes. Acknowledgement and awareness of the factors that influence help seeking will aid the design of gender specific promotion, prevention, and treatment programmes at primary care level.
The Dying Rabbit Problem Revisited
Authors: Oller-Marcén Antonio M. 
Published: June 2009

AbstractIn this paper we study a generalization of the Fibonacci sequence in which rabbits are mortal and take more that two months to become mature. In particular we give a general recurrence relation for these sequences (improving the work in [Hoggat and Lind, Fibonacci Quart. 7: 482–487, 1969]) and we calculate explicitly their general term (extending the work in [Miles, Amer. Math. Monthly 67: 745–752, 1960]). In passing, and as a technical requirement, we also study the behavior of the positive real roots of the characteristic polynomial of the considered sequences.
Generalized Levinson–Durbin Sequences and Binomial Coefficients
Authors: Shaman Paul 
Published: June 2009

AbstractThe Levinson–Durbin recursion is used to construct the coefficients which define the minimum mean square error predictor of a new observation for a discrete time, second-order stationary stochastic process. As the sample size varies, the coefficients determine what is called a Levinson–Durbin sequence. A generalized Levinson–Durbin sequence is also defined, and we note that binomial coefficients constitute a special case of such a sequence. Generalized Levinson–Durbin sequences obey formulas which generalize relations satisfied by binomial coefficients. Some of these results are extended to vector stationary processes.
Contaminated Sediment Management by Capping and Deep Water Confined Aquatic Disposal in the Harbor of Oslo
Authors: Breedveld Gijs D. , Pettersen Arne , Oen Amy M. P. , Eek Espen , Cornelissen Gerard , Kibsgaard Anne , Hauge Audun , Jørgensen Torild , Jensen Kjetil Lønborg 
Published: June 2009

Abstract
Dredging has been prohibited in the harbor of Oslo in the past 15 years as a result of serious sediment contamination. Through a joint effort of the Oslo Harbor Authorities, the Norwegian Road Administration, and the Norwegian Pollution Control Authorities, a remediation plan for the redevelopment of the old harbor of Oslo has been implemented. The plan, which will be completed in 2009, includes dredging of the shallow parts of the harbor down to 15 m of water depth (approximately 450,000 m3), capping of the deeper parts of the harbor (1,000,000 m2), as well as construction of a deep water confined aquatic disposal facility for the dredged material at 70-m depth in the inner Oslofjord. To prevent uncontrolled contaminant transport, an on-line monitoring system is operated that consists of buoys with turbidity loggers and a water current velocity meter. Passive samplers are used for time-integrated sampling of organic contaminants. In addition, periodic sampling and analysis of water and suspended solid samples are carried out. To document the environmental benefit from the remediation, contaminant transport is quantified before, during, and after remediation using flux measurements based on in situ diffusion chambers. Monitoring results show that remobilization of contaminants has been very limited and do not exceed the amounts defined in the environmental permit from the pollution control authorities (environmental budget). Capping resulted in more than 90 % reduction in contaminant flux.