bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase 0 Clinical Trial of the Poly (ADP-Ribose) Polymerase Inhibitor ABT-888 in Patients With Advanced Malignancies
Authors: Kummar Shivaani , Kinders Robert , Gutierrez Martin E. , Rubinstein Larry , Parchment Ralph E. , Phillips Lawrence R. , Ji Jiuping , Monks Anne , Low Jennifer A. , Chen Alice , Murgo Anthony J. , Collins Jerry , Steinberg Seth M. , Eliopoulos Helen , Giranda Vincent L. , Gordon Gary , Helman Lee , Wiltrout Robert , Tomaszewski Joseph E. , Doroshow James H. 
Published: April 2009

Purpose We conducted the first phase 0 clinical trial in oncology of a therapeutic agent under the Exploratory Investigational New Drug Guidance of the US Food and Drug Administration. It was a first-in-human study of the poly (ADP-ribose) polymerase (PARP) inhibitor ABT-888 in patients with advanced malignancies. Patients and Methods ABT-888 was administered as a single oral dose of 10, 25, or 50 mg to determine the dose range and time course over which ABT-888 inhibits PARP activity in tumor samples and peripheral blood mononuclear cells, and to evaluate ABT-888 pharmacokinetics. Blood samples and tumor biopsies were obtained pre- and postdrug administration for evaluation of PARP activity and pharmacokinetics. A novel statistical approach was developed and utilized to study pharmacodynamic modulation as the primary end point for trials of limited sample size. Results Thirteen patients with advanced malignancies received the study drug; nine patients underwent paired tumor biopsies. ABT-888 demonstrated good oral bioavailability and was well tolerated. Statistically significant inhibition of poly (ADP-ribose) levels was observed in tumor biopsies and peripheral blood mononuclear cells at the 25-mg and 50-mg dose levels. Conclusion Within 5 months of study activation, we obtained pivotal biochemical and pharmacokinetic data that have guided the design of subsequent phase I trials of ABT-888 in combination with DNA-damaging agents. In addition to accelerating the development of ABT-888, the rapid conclusion of this trial demonstrates the feasibility of conducting proof-of-principle phase 0 trials as part of an alternative paradigm for early drug development in oncology.
Fertility of Female Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study
Authors: Green Daniel M. , Kawashima Toana , Stovall Marilyn , Leisenring Wendy , Sklar Charles A. , Mertens Ann C. , Donaldson Sarah S. , Byrne Julianne , Robison Leslie L. 
Published: April 2009

Purpose This study was undertaken to determine the effect, if any, of treatment for cancer diagnosed during childhood or adolescence on fertility. Patients and Methods We reviewed the fertility of female participants in the Childhood Cancer Survivor Study (CCSS), which consisted of 5-year survivors, and a cohort of randomly selected siblings who responded to a questionnaire. Medical records of all members of the cohort were abstracted to obtain chemotherapeutic agents administered; the cumulative dose of drug administered for several drugs of interest; and the doses, volumes, and dates of administration of all radiation therapy. Results There were 5,149 female CCSS participants, and there were 1,441 female siblings of CCSS participants who were age 15 to 44 years. The relative risk (RR) for survivors of ever being pregnant was 0.81 (95% CI, 0.73 to 0.90; P < .001) compared with female siblings. In multivariate models among survivors only, those who received a hypothalamic/pituitary radiation dose ≥ 30 Gy (RR, 0.61; 95% CI, 0.44 to 0.83) or an ovarian/uterine radiation dose greater than 5 Gy were less likely to have ever been pregnant (RR, 0.56 for 5 to 10 Gy; 95% CI, 0.37 to 0.85; RR, 0.18 for > 10 Gy; 95% CI, 0.13 to 0.26). Those with a summed alkylating agent dose (AAD) score of three or four or who were treated with lomustine or cyclophosphamide were less likely to have ever been pregnant. Conclusion This large study demonstrated that fertility is decreased among female CCSS participants. The risk factors identified may be utilized for pretreatment counseling of patients and their parents.
Reticulin Accumulation in Essential Thrombocythemia: Prognostic Significance and Relationship to Therapy
Authors: Campbell Peter J. , Bareford David , Erber Wendy N. , Wilkins Bridget S. , Wright Penny , Buck Georgina , Wheatley Keith , Harrison Claire N. , Green Anthony R. 
Published: April 2009

Purpose Essential thrombocythemia (ET) manifests substantial interpatient heterogeneity in rates of thrombosis, hemorrhage, and disease transformation. Bone marrow histology reflects underlying disease activity in ET but many morphological features show poor reproducibility. Patients and Methods We evaluated the clinical significance of bone marrow reticulin, a measure previously shown to have relatively high interobserver reliability, in a large, prospectively-studied cohort of ET patients. Results Reticulin grade positively correlated with white blood cell (P = .05) and platelet counts (P = .0001) at diagnosis. Elevated reticulin levels at presentation predicted higher rates of arterial thrombosis (hazard ratio [HR], 1.8; 95% CI, 1.1 to 2.9; P = .01), major hemorrhage (HR, 2.0; 95% CI, 1.0 to 3.9; P = .05), and myelofibrotic transformation (HR, 5.5; 95% CI, 1.7 to 18.4; P = .0007) independently of known risk factors. Higher reticulin levels at diagnosis were associated with greater subsequent falls in hemoglobin levels in patients treated with anagrelide (P < .0001), but not in those receiving hydroxyurea (P = .9). Moreover, serial trephine specimens in patients randomly assigned to anagrelide showed significantly greater increases in reticulin grade compared with those allocated to hydroxyurea (P = .0003), and four patients who developed increased bone marrow reticulin on anagrelide showed regression of fibrosis when switched to hydroxyurea. These data suggest that patients receiving anagrelide therapy should undergo surveillance bone marrow biopsy every 2 to 3 years and that those who show substantially increasing reticulin levels are at risk of myelofibrotic transformation and may benefit from changing therapy before adverse clinical features develop. Conclusion Our results demonstrate that bone marrow reticulin grade at diagnosis represents an independent prognostic marker in ET, reflecting activity and/or duration of disease, with implications for the monitoring of patients receiving anagrelide.
Phase I Study of Samarium-153 Lexidronam With Docetaxel in Castration-Resistant Metastatic Prostate Cancer
Authors: Morris Michael J. , Pandit-Taskar Neeta , Carrasquillo Jorge , Divgi Chaitanya R. , Slovin Susan , Kelly William K. , Rathkopf Dana , Gignac Gretchen A. , Solit David , Schwartz Lawrence , Stephenson Ryan D. , Hong Christina , Delacruz Anthony , Curley Tracy , Heller Glenn , Jia Xiaoyu , O'Donoghue Joseph , Larson Steven , Scher Howard I. 
Published: April 2009

Purpose Early studies of patients with castration-resistant metastatic prostate cancer (CRMPC) suggest that chemotherapy administered with a dose of a bone-seeking radiopharmaceutical is superior to chemotherapy alone. To build on this strategy and fully integrate a repetitively dosed bone-seeking radiopharmaceutical into a contemporary chemotherapy regimen, we conducted a phase I study of docetaxel and samarium-153 (153Sm) lexidronam. Patients and Methods Men with progressive CRMPC were eligible. Cohorts of three to six patients were defined by dose escalations as follows: docetaxel 65, 70, 75, 75, 75 mg/m2 and 153Sm ethylenediaminetetramethylenephosphonate (EDTMP) 0.5, 0.5, 0.5, 0.75, 1 mCi/kg. Each cycle lasted a minimum of 6 (cohorts 1 through 5) or 9 (cohort 6) weeks. Docetaxel was administered on days 1 and 22 (and day 43 for cohort 6), and 153Sm-EDTMP was administered on day −1 to 1 of each cycle. Patients with acceptable hematologic toxicities were eligible to receive additional cycles until progression. Results Twenty-eight men were treated in six cohorts. Maximum-tolerated dose was not reached, because full doses of both agents were well tolerated, even using an every-6-week dosing schedule of 153Sm-EDTMP. Patients received an average of 5.6 docetaxel doses (range, one to 13 doses) and 2.9 153Sm-EDTMP doses (range, one to six doses). Fifteen patients demonstrated a more than 50% decline in prostate-specific antigen. Treatment significantly reduced indices of bone deposition and resorption. Conclusion Docetaxel and 153Sm-EDTMP can be combined safely at full doses over repeated cycles. Responses were seen in the small group of patients with taxane-resistant disease tested. The optimal phase II doses for patients with taxane-naïve disease may differ from those optimal for patients with taxane-resistant disease.
Factors Associated With Living in Developmental Centers in California
Authors: Harrington Charlene , Kang Taewoon , Chang Jamie 
Published: April 2009

AbstractThis study examined need, predisposing, market, and regional factors that predicted the likelihood of individuals with developmental disabilities living in state developmental centers (DCs) compared with living at home, in community care, or in intermediate care (ICFs) and other facilities. Secondary data analysis using logistic regression models was conducted for all individuals ages 21 years or older who had moderate, severe, or profound intellectual disability. Client needs were the most important factors associated with living arrangements, with those in DCs having more complex needs. Men had higher odds of living in DCs than in other settings, whereas older individuals had lower odds of living in DCs than in ICFs for persons with developmental disabilities and other facilities. Asians/Pacific Islanders, African Americans, and Hispanics were less likely to live in DCs than to live at home. The supply of residential care beds for the elderly reduced the likelihood of living in DCs, and the odds of living in a DC varied widely across regions. Controlling for need, many other factors predicted living arrangements. Policymakers need to ensure adequate resources and provider supply to reduce the need by individuals with intellectual disability to live in DCs and to transition individuals from DCs into other living arrangements.
Satisfaction and Sense of Well Being Among Medicaid ICF/MR and HCBS Recipients in Six States
Authors: Stancliffe Roger J. , Lakin K. Charlie , Taub Sarah , Chiri Giuseppina , Byun Soo-yong 
Published: April 2009

Abstract
Self-reported satisfaction and sense of well-being were assessed in a sample of 1,885 adults with intellectual and developmental disabilities receiving Medicaid Home and Community Based Services (HCBS) and Intermediate Care Facility (ICF/MR) services in 6 states. Questions dealt with such topics as loneliness, feeling afraid at home and in one's neighborhood, feeling happy, feeling that staff are nice and polite, and liking one's home and work/day program. Loneliness was the most widespread problem, and there were also small percentages of people who reported negative views in other areas. Few differences were evident by HCBS and ICF/MR status. The findings document consistent benefits of residential support provided in very small settings—with choices of where and with whom to live—and to individuals living with family.
Social Inclusion of Children With Intellectual Disabilities in a Recreational Setting
Authors: Siperstein Gary N. , Glick Gary C. , Parker Robin C. 
Published: April 2009

Abstract
The social acceptance of children with and without intellectual disabilities was examined in an inclusive, summer recreational program. Participants were 67 children entering Grades 3 through 6, of which 29 were identified as having a mild intellectual disability. Children were recruited from economically and racially diverse urban school districts. Results showed that children with and without intellectual disabilities were equally accepted by their peers. Specifically, 95% of children without intellectual disabilities indicated that they liked to “hang out with” at least 1 child with an intellectual disability. Results also indicated that the majority of children without intellectual disabilities made at least 1 new friend with another child with an intellectual disability. The features of recreational programming that promote social inclusion are discussed.
Numerical Simulation of the Mechanical Properties of Cr12 Steel during Gas Quenching
Authors: Li Ziliang , Cheng Heming , Li Jianyun , Hou Lijun 
Published: April 2009

Abstract
Heat treatment is one method to improve mechanical properties of metal, but each heat treatment method has its advantages and disadvantages, therefore, different requirements regarding size, shape, and properties with respect to different heat treatment processes should be considered. Gas quenching is a heat treatment process used in various industries such as the aerospace, automotive, machine tool, and other advanced manufacturing processes. The use of gas quenching can significantly improve the mechanical and physical properties of a material. Simulation of gas quenching processes is becoming increasingly important, although not common, for the investigation of mechanical properties and their effects on quality. This paper is based on the theory of phase transformation, computational mechanics, thermal nonelasticity, and the character of the gas quenching process. A nonlinear heat conduction equation considering phase transformation is developed and a model of the relationship between the phase transformation products and the properties of Cr12 steel are established and solved using the finite element method (FEM). By comparing calculated results with those of experiments, satisfying agreement is found. It is anticipated that this model will be valuable for further theoretical development and practical applications.
Evolution of New Disease Specificity at a Simple Resistance Locus in a Crop–Weed Complex: Reconstitution of theLr21Gene in Wheat
Authors: Huang Li , Brooks Steven , Li Wanlong , Fellers John , Nelson James C , Gill Bikram 
Published: April 2009

AbstractThe wheat leaf-rust resistance gene Lr21 was first identified in an Iranian accession of goatgrass, Aegilops tauschii Coss., the D-genome donor of hexaploid bread wheat, and was introgressed into modern wheat cultivars by breeding. To elucidate the origin of the gene, we analyzed sequences of Lr21 and lr21 alleles from 24 wheat cultivars and 25 accessions of Ae. tauschii collected along the Caspian Sea in Iran and Azerbaijan. Three basic nonfunctional lr21 haplotypes, H1, H2, and H3, were identified. Lr21 was found to be a chimera of H1 and H2, which were found only in wheat. We attempted to reconstitute a functional Lr21 allele by crossing the cultivars Fielder (H1) and Wichita (H2). Rust inoculation of 5876 F2 progeny revealed a single resistant plant that proved to carry the H1H2 haplotype, a result attributed to intragenic recombination. These findings reflect how plants balance the penalty and the necessity of a resistance gene and suggest that plants can reuse “dead” alleles to generate new disease-resistance specificity, leading to a “death–recycle” model of plant-resistance gene evolution at simple loci. We suggest that selection pressure in crop–weed complexes contributes to this process.
Distal Recognition Sites in Substrates Are Required for Efficient Phosphorylation by the cAMP-Dependent Protein Kinase
Authors: Deminoff Stephen J , Ramachandran Vidhya , Herman Paul K 
Published: April 2009

Abstract
Protein kinases are important mediators of signal transduction in eukaryotic cells, and identifying the substrates of these enzymes is essential for a complete understanding of most signaling networks. In this report, novel substrate-binding variants of the cAMP-dependent protein kinase (PKA) were used to identify substrate domains required for efficient phosphorylation in vivo. Most wild-type protein kinases, including PKA, interact only transiently with their substrates. The substrate domains identified were distal to the sites of phosphorylation and were found to interact with a C-terminal region of PKA that was itself removed from the active site. Only a small set of PKA alterations resulted in a stable association with substrates, and the identified residues were clustered together within the hydrophobic core of this enzyme. Interestingly, these residues stretched from the active site of the enzyme to the C-terminal substrate-binding domain identified here. This spatial organization is conserved among the entire eukaryotic protein kinase family, and alteration of these residues in a second, unrelated protein kinase also resulted in a stable association with substrates. In all, this study identified distal sites in PKA substrates that are important for recognition by this enzyme and suggests that the interaction of these domains with PKA might influence specific aspects of substrate binding and/or release.
Psychiatric Characteristics in a Self-Selected Sample of Boys With Klinefelter Syndrome
Authors: Bruining Hilgo , Swaab Hanna , Kas Martien , van Engeland Herman 
Published: April 2009

BACKGROUND. Klinefelter syndrome is the most frequent chromosomal aneuploidy with a prevalence of 1 in 700. Klinefelter syndrome has been widely associated with cognitive impairment and language problems. No previous studies have systematically investigated the association of Klinefelter syndrome with psychiatric disorders in children and adolescents. To our knowledge, the only data available are from psychiatric inventories of adults with Klinefelter syndrome.OBJECTIVE. To explore the extent of psychiatric morbidity in children with Klinefelter syndrome.METHOD. Fifty-one subjects with Klinefelter syndrome aged 6 to 19 years were included through the Dutch Klinefelter association and 2 university medical centers. The sample was screened by using structured and standardized assessment procedures covering the full range of psychiatric problems and disorders. In addition, all boys were formally evaluated for the presence of a language disorder.RESULTS. A wide range of classifications could be applied, with language disorder (65% [33 of 51]) as the most prevalent disorder, followed by attention-deficit disorders (63% [32 of 51]) and autism spectrum disorder (27% [14 of 51]). Behavioral impairment was most evident among cases classified as autism spectrum disorder and psychotic disorder (12% [6 of 51]).CONCLUSIONS. Children with Klinefelter syndrome seem to be at risk for problems in social and language development, as well as for problems in regulation of emotion and behavior. This is reflected in the broad spectrum of psychiatric classifications applicable in the present selected sample. Health care professionals should be aware of an increased a priori possibility of psychiatric problems when confronted with a child with Klinefelter syndrome.
Managing Iron Overload in Patients with Myelodysplastic Syndromes with Oral Deferasirox Therapy
Authors: Jabbour Elias , Garcia-Manero Guillermo , Taher Ali , Kantarjian Hagop M. 
Published: April 2009

AbstractPatients with myelodysplastic syndromes (MDS) often require chronic RBC transfusions, which can lead to iron overload. Without adequate management, this may cause progressive damage to hepatic, endocrine, and cardiac organs, significantly affecting overall survival. Recent retrospective analyses have suggested that iron chelation provides a survival advantage in iron-overloaded patients with MDS who are given chelation therapy compared with those who are not. Nonetheless, it is evident that iron overload in many patients with MDS is not adequately managed. Clinical evaluation of the once-daily, oral iron chelator deferasirox in MDS populations has indicated that it provides dose-dependent reductions in body iron burden and is generally well tolerated, with a manageable safety profile in adult and pediatric patients. The most common treatment-related adverse events (AEs) included transient, mild-to-moderate gastrointestinal disturbances and skin rash, which rarely required drug discontinuation and resolved spontaneously in most cases. Adequate management of AEs and practical approaches such as patient education and counseling are necessary to ensure that patients remain compliant with therapy. Regular monitoring of serum ferritin levels is key to identifying patients who require iron chelation therapy, and to ensure maintenance of iron levels below the critical level of 1,000 μg/l. The flexible dosing regimen of deferasirox allows dose adjustments to be made in response to trends in serum ferritin, to changes in a patient’s transfusional iron intake, and to the objectives of treatment, allowing the full benefit of transfusion therapy without the risks associated with iron overload.
Environmental properties of pentafluorosulfanyl compounds: Physical properties and photodegradation
Authors: Jackson Derek A. , Mabury Scott A. 
Published: April 2009

Abstract
The pentafluorosulfanyl (SF5) functional group was investigated from an environmental perspective to ascertain its physical properties and photolytic fate. Five aromatic probe compounds were compared with their trifluoromethyl analogs. Water solubilities for SF5 compounds ranged from 78 mg/L to 2.4 g/L. Octanol—water partitioning coefficients ranged from log Kow = 2.9 to 3.6, all of which were approximately 0.5 to 0.6 log units more hydrophobic than their trifluoromethyl analogs. The direct photolytic fate of SF5 compounds was studied, and the SF5 group was found to completely degrade using actinic radiation with hourly half-lives. The reaction was followed by high-performance liquid chromatography with a UV-visible detector, 19F nuclear magnetic resonance spectroscopy, and high-resolution mass spectrometry. It was found that five equivalents of fluoride were released to form a benzenesulfonate as a final product of photodegradation. Finally, an SF5 analog of fluometuron, a potentially new herbicide, was synthesized and likewise photolyzed. The present study provides the first evidence that pentafluorosulfanyl can degrade under mild, environmentally relevant conditions.
ME Surfactant Increases Production in the Codell Formation of the DJ Basin
Authors: Paterniti M. 
Published: April 2009

Abstract
A Denver-Julesburg (DJ) Basin operator, Anadarko Petroleum Corp., has had success with the optimization of its completions in the Codell formation. The use of a microemulsion additive (ME) is one of the keys that has allowed them to further improve production and increase reserves.
Before the ME surfactant, the operator used a non-emulsifier (NE) as a surfactant in their stimulation treatments. By replacing the surfactant with the ME, their median production has increased by 10%. In addition, lower GOR wells show the most benefit from the use of the ME additive, meaning that margins on wells in lower GOR areas can be improved. Anadarko began testing the ME additive in 2005 while still completing some Codell wells with the NE. After review, the ME additive was run almost exclusively.
This paper compares the wells using ME to those using the conventional NE surfactant. The study wells were chosen to minimize potential production effects caused by other factors, such as job size and depletion. After eliminating these other factors, the sample size consisted of 32 NE wells and 34 ME wells across the basin. The wells were compared on a broad scope and where possible, offset wells were compared.