bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultimate Fate of Oncology Drugs Approved by the US Food and Drug Administration Without a Randomized Trial
Authors: Tsimberidou Apostolia-Maria , Braiteh Fadi , Stewart David J. , Kurzrock Razelle 
Published: October 2009

PurposeTo approve a new anticancer drug, the US Food and Drug Administration often requires randomized trials. However, several oncology drugs have been approved on the basis of objective end points without a randomized trial. We reviewed the long-term safety and efficacy of such agents.MethodsWe searched the Web site of the US Food and Drug Administration's Center for Drug Evaluation and Research and MEDLINE for initial applications of investigational anticancer drugs from 1973 through 2006.ResultsOverall, 68 oncology drugs, excluding hormone therapy and supportive care, were approved, including 31 without a randomized trial. For these 31 drugs, a median of two clinical trials (range, one to seven) and 79 patients (range, 40 to 413) were used per approval. Objective response was the most common end point used for approval; median response rate was 33% (range, 11% to 90%). Thirty drugs are still fully approved. United States marketing authorization for one drug, gefitinib (an epidermal growth factor receptor [EGFR] inhibitor), was rescinded after a randomized trial showed no survival improvement; however, this trial was performed in unselected patients, and it was subsequently demonstrated that patients with EGFR mutation are more likely to respond. Nineteen of the 31 drugs have additional uses (per National Comprehensive Cancer Network or National Cancer Institute Physician Data Query guidelines), and subsequent formal US Food and Drug Administration approvals were obtained for 11 of these (range, one to 18 new indications). No drug has demonstrated safety concerns.ConclusionNonrandomized clinical trials with definitive end points can yield US Food and Drug Administration approvals, and these drugs have a reassuring record of long-term safety and efficacy.
Meeting New Challenges in the Management of Anemia of Chronic Kidney Disease Through Collaborative Care with Pharmacists
Authors: Bacchus Shaffeeulah , O'mara Neeta , Manley Harold , Fishbane Steven 
Published: October 2009

Objective: To evaluate chronic kidney disease (CKD)–associated anemia management challenges and limitations and discuss strategies to improve treatment rates and patient response to therapy, monitoring of patient response to therapy, and education of prescribing providers and patients. Data Sources: Multiple MEDLINE searches were performed using a comprehensive search term list to identify studies for inclusion, including, but not limited to, anemia, erythropoiesis-stimulating agent (ESA), epoetin, darbepoetin, CERA, hemoglobin, CKD, dialysis, end-stage renal disease, quality of life, and pharmacist. Annual data reports and clinical practice guidelines published by the National Kidney Foundation and US Renal Data System were included. Information provided within product package inserts for recombinant human erythropoietin (epoetin alfa; Epogen, Procrit) and darbepoetin alfa (Aranesp) were also included. Study Selection and Data Extraction: Only articles that were published in English and were relevant for this review were included. Data Synthesis: Anemia is a common complication of CKD, with significant impact on patients' quality of life. Anemia of CKD represents a significant burden on the healthcare system, with ESA use resulting in substantial financial costs. As new therapies, formularies, and dosing regimens evolve, the collaborative role of the clinical pharmacist is integral to a multidisciplinary treatment strategy, both in the inpatient and outpatient settings, such as hospitals or dialysis centers, respectively. This review focuses on initial and target hemoglobin (Hb) concentrations, as well as patient characteristics, treatment preferences, and dosing schedules, which are important considerations in managing CKD-associated anemia. To ensure effective therapeutic strategies, a patient-centered approach is required. Pharmacists are ideally positioned to help select ESA therapy, influence formulary use, educate healthcare professionals and patients, develop and implement dosing and monitoring protocols, and possibly promote quality improvement. Conclusions: An approach to CKD-associated anemia management that involves collaboration with pharmacists is essential to achieve patient-specific, cost-effective ESA therapy.
Sliding Scale Versus Tight Glycemic Control in the Noncritically III at a Community Hospital
Authors: Patel Gita Wasan , Roderman Nicki , Lee Karen A , Charles Melissa M , Nguyen Diem , Beougher Paula , Kleja Kacie , Casteneda Evangelina 
Published: October 2009

Background: Development of hyperglycemia during hospitalization is an area of concern in patients with and without diabetes mellitus. Tight glycemic control has been debated for critically ill and noncritically III patients with hyperglycemia. Although many studies have been performed in the critically ill, adequate data are not available in the noncritically ill population. Objective: To compare traditional sliding scale (SS) with a tight glycemic control (TC) algorithm. The primary endpoint was the percentage of total blood glucose measurements in the target range of 80–150 mg/dL. The secondary endpoint evaluated was safety, defined as percentage of all blood glucose measurements that were 0–60 mg/dL. Methods: A 1-year, retrospective analysis from June 1, 2007, to May 31, 2008, was performed evaluating all inpatients with hyperglycemia within the first 48 hours of admission to the Medical Center of Plano, Plano, TX. A cohort of patients managed with SS (n =121) was compared with those treated with TC (n = 210). Patients on SS insulin received a traditional SS regimen with regular insulin or insulin aspart based on physician preference. Results: Demographics and comorbidities were similar between the 2 groups; however, the TC cohort was younger (64.8 ± 14.1 vs 70.8 ± 13.7 y; p< 0.001). There were more persons with type 2 diabetes mellitus in the TC cohort (81.9%) versus the SS cohort (60.3%; p < 0.001). In the TC cohort, 42.9% of blood glucose measurements were in the target range of 80–150 mg/dL compared with 30.6% of the measurements in the SS cohort (p < 0.001). Regarding safety, 2% of blood glucose measurements of the TC cohort were in the range of 0–60 mg/dL versus 0.3% of the SS cohort (p < 0.001). No clinical sequelae of hypoglycemia were observed. Patients achieved more blood glucose measurements in the target range when treated with TC versus SS insulin, without regard to prior history of diabetes. Conclusions: Patients treated with TC experienced more blood glucose measurements in the target range as compared with patients treated with SS with relatively low hypoglycemia rates.
Neonatal Peritoneal Candidiasis Successfully Treated with Anidulafungin Add-On Therapy
Authors: Varisco Brian Michael , Benner Kimberley W , Prabhakaran Priya 
Published: October 2009

Objective: To report the first successful use of anidulafungin and liposomal amphotericin B in an infant with peritoneal candidiasis. Case Summary: An 11-day-old term female infant with Hirschsprung enterocolitis and bowel perforation was transferred to our institution on day 4 of hospitalization with septic shock and abdominal compartment syndrome. Initial peritoneal culture at time of colectomy did not grow yeast; however, Candida albicans grew from cultures obtained on abdominal washout 2 days later even while the patient was on treatment with liposomal amphotericin B 5 mg/kg/day. Anidulafungin 1.5 mgkg/day intravenous therapy was instituted, and within 4 days peritoneal cultures were negative. The patient slowly recovered and, after a prolonged hospitalization, she was discharged home on hospital day 68 on partial parenteral nutrition. Discussion: Despite the rising incidence of fluconazole-resistant Candida spp., pediatric dosing guidelines, and an adult indication for echinocandin use in candidal peritonitis, there are no reports of echinocandin use for fungal peritonitis in pediatric patients. The echinocandins are rational choices when fluconazole resistance is a concern. Furthermore, the unique clearance profile of anidulafungin makes it an attractive choice in critically ill patients with hepatic and renal dysfunction; the Infectious Diseases Society of America has recommended that an echinocandin be first-line antifungal therapy for moderately or severely ill pediatric or adult patients. Conclusions: Peritoneal candidiasis is a common complication of bowel perforation in neonates. Anidulafungin's pharmacokinetic and antifungal properties make it a viable therapeutic option in the treatment of this disease in critically ill infants and children.
Electron Scattering in Buried InGaAs MOSFET Channel with HfO2Gate Oxide
Authors: Oktyabrsky Serge , Nagaiah Padmaja , Tokranov Vadim , Koveshnikov Sergei , Yakimov Michael , Kambhampati Rama , Moore Richard , Tsai Wilman 
Published: October 2009

AbstractGroup III-V semiconductor materials are being studied as potential replacements for conventional CMOS technology due to their better electron transport properties. However, the excess scattering of carriers in MOSFET channel due to high-k gate oxide interface significantly depreciates the benefits of III-V high-mobility channel materials. We present results on Hall electron mobility of buried QW structures influenced by remote scattering due to InGaAs/HfO2interface. Mobility in In0.77Ga0.23As QWs degraded from 12000 to 1200 cm2/V-s and the mobility vs. temperature slope changed from T-1.2to almost T+1.0in 77-300 K range when the barrier thickness is reduced from 50 to 0 nm. This mobility change is attributed to remote Coulomb scattering due to charges and dipoles at semiconductor/oxide interface. Elimination of the InGaAs/HfO2interface via introduction of SiOxinterface layer formed by oxidation of thin a-Si passivation layer was found to improve the channel mobility. The mobility vs. sheet carrier density shows the maximum close to 2×1012cm-2.
First Principles Study of Metal/Bi2Te3Interfaces: Implications to Improve Contact Resistance
Authors: Xiong Ka , Wang Weichao , Alshareef Husam N , Gupta Rahul P , White John B , Gnade Bruce E , Cho Kyeongjae 
Published: October 2009

AbstractWe investigate the band offsets and stability for Ni/Bi2Te3and Co/Bi2Te3interfaces by first principles calculations. It is found that the surface termination strongly affects the band offsets. Ni and Co are found to form Ohmic contacts to Bi2Te3. The interface formation energies for Co/Bi2Te3interfaces are much lower than those of Ni/Bi2Te3interfaces. Our calculations are consistent with the experimental data.
Physics based models for metal hydride particle morphology, distribution, and effective thermal conductivity
Authors: Smith Kyle Christopher , Fisher Timothy 
Published: October 2009

AbstractThis paper describes a modeling approach to target aspects of heat conduction in metal hydride powders that are essential to metal hydrides as viable H2storage media, including particle morphology distribution, size distribution, particle packing properties at specified solid fraction, and effective thermal conductivity. An isotropic fracture model is presented that replicates features of particle size and shape distributions observed experimentally. The discrete element method is used to simulate evolution of metal hydride particle contact networks during quasi-static consolidation of decrepitated metal hydride powders. Finally, the effective thermal conductivity of such a powder is modeled assuming that contact conductance is the same for each interparticle contact.
Overexpression of Kinase-Negative Protein Kinase Cδ in Pancreatic β-Cells Protects Mice From Diet-Induced Glucose Intolerance and β-Cell Dysfunction
Authors: Hennige Anita M. , Ranta Felicia , Heinzelmann Isabel , Düfer Martina , Michael Diana , Braumüller Heidi , Lutz Stefan Z. , Lammers Reiner , Drews Gisela , Bosch Fatima , Häring Hans-Ulrich , Ullrich Susanne 
Published: October 2009

OBJECTIVE
In vitro models suggest that free fatty acid–induced apoptotic β-cell death is mediated through protein kinase C (PKC)δ. To examine the role of PKCδ signaling in vivo, transgenic mice overexpressing a kinase-negative PKCδ (PKCδKN) selectively in β-cells were generated and analyzed for glucose homeostasis and β-cell survival.

RESEARCH DESIGN AND METHODS
Mice were fed a standard or high-fat diet (HFD). Blood glucose and insulin levels were determined after glucose loads. Islet size, cleaved caspase-3, and PKCδ expression were estimated by immunohistochemistry. In isolated islet cells apoptosis was assessed with TUNEL/TO-PRO3 DNA staining and the mitochondrial potential by rhodamine-123 staining. Changes in phosphorylation and subcellular distribution of forkhead box class O1 (FOXO1) were analyzed by Western blotting and immunohistochemistry.

RESULTS
PKCδKN mice were protected from HFD-induced glucose intolerance. This was accompanied by increased insulin levels in vivo, by an increased islet size, and by a reduced staining of β-cells for cleaved caspase-3 compared with wild-type littermates. In accordance, long-term treatment with palmitate increased apoptotic cell death of isolated islet cells from wild-type but not from PKCδKN mice. PKCδKN overexpression protected islet cells from palmitate-induced mitochondrial dysfunction and inhibited nuclear accumulation of FOXO1 in mouse islet and INS-1E cells. The inhibition of nuclear accumulation of FOXO1 by PKCδKN was accompanied by an increased phosphorylation of FOXO1 at Ser256 and a significant reduction of FOXO1 protein.

CONCLUSIONS
Overexpression of PKCδKN in β-cells protects from HFD-induced β-cell failure in vivo by a mechanism that involves inhibition of fatty acid–mediated apoptosis, inhibition of mitochondrial dysfunction, and inhibition of FOXO1 activation.
Ethnic Differences in the Relationship Between Albuminuria and Calcified Atherosclerotic Plaque
Authors: Divers Jasmin , Wagenknecht Lynne E. , Bowden Donald W. , Carr J. Jeffrey , Hightower R. Caresse , Xu Jianzhao , Langefeld Carl D. , Freedman Barry I. 
Published: October 2009

OBJECTIVEDespite higher rates of nephropathy, calcified atherosclerotic plaque is less prevalent in African Americans with diabetes relative to European Americans. We explored ethnicity-specific relationships between albuminuria and calcified plaque involving the infrarenal aorta, coronary artery, and carotid artery in 835 European American and 393 African American subjects with type 2 diabetes.RESEARCH DESIGN AND METHODSGeneralized estimating equations with exchangeable correlation and the sandwich estimator of the variance were used to test for association between the principal component of calcified plaque in the three vascular beds and urine albumin-to-creatinine ratio (ACR).RESULTSMean ± SD ages of African American and European American participants were 56.7 ± 9.6 and 61.7 ± 9.1 years, respectively, with diabetes duration of 10.4 ± 7.4 and 10.0 ± 7.3 years and median urine ACR of 17.5 and 13.4 mg/g. In African American and European American participants, respectively, median calcified plaque mass scores were 53.5 and 291 for coronary artery, 3 and 35.5 for carotid artery, and 761 and 3,237 for aorta. With adjustment for age, sex, glomerular filtration rate, and BMI, albuminuria was significantly associated with calcified plaque in European Americans (P = 3.4 × 10−8) but not in African Americans (P = 0.33), with significant ethnic interaction (P = 0.01). Ethnic differences in this relationship persisted after adjustment for blood pressure, smoking, lipids, and use of ACE inhibitors or angiotensin receptor blockers.CONCLUSIONSAlbuminuria is strongly associated with severity of calcified plaque in European Americans with diabetes but not in African Americans. Disparities in this relationship may contribute to ethnic differences in the rates of cardiovascular disease that are observed in subjects with type 2 diabetes.
Dietary Intake of Total, Animal, and Vegetable Protein and Risk of Type 2 Diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-NL Study
Authors: Sluijs Ivonne , Beulens Joline W.J. , van der A Daphne L. , Spijkerman Annemieke M.W. , Grobbee Diederick E. , van der Schouw Yvonne T. 
Published: October 2009

OBJECTIVE
Dietary recommendations are focused mainly on relative dietary fat and carbohydrate content in relation to diabetes risk. Meanwhile, high-protein diets may contribute to disturbance of glucose metabolism, but evidence from prospective studies is scarce. We examined the association among dietary total, vegetable, and animal protein intake and diabetes incidence and whether consuming 5 energy % from protein at the expense of 5 energy % from either carbohydrates or fat was associated with diabetes risk.

RESEARCH DESIGN AND METHODS
A prospective cohort study was conducted among 38,094 participants of the European Prospective Investigation into Cancer and Nutrition (EPIC)-NL study. Dietary protein intake was measured with a validated food frequency questionnaire. Incident diabetes was verified against medical records.

RESULTS
During 10 years of follow-up, 918 incident cases of diabetes were documented. Diabetes risk increased with higher total protein (hazard ratio 2.15 [95% CI 1.77–2.60] highest vs. lowest quartile) and animal protein (2.18 [1.80–2.63]) intake. Adjustment for confounders did not materially change these results. Further adjustment for adiposity measures attenuated the associations. Vegetable protein was not related to diabetes. Consuming 5 energy % from total or animal protein at the expense of 5 energy % from carbohydrates or fat increased diabetes risk.

CONCLUSIONS
Diets high in animal protein are associated with an increased diabetes risk. Our findings also suggest a similar association for total protein itself instead of only animal sources. Consumption of energy from protein at the expense of energy from either carbohydrates or fat may similarly increase diabetes risk. This finding indicates that accounting for protein content in dietary recommendations for diabetes prevention may be useful.
High‐Resolution Patterning of Hydrogels in Three Dimensions using Direct‐Write Photofabrication for Cell Guidance
Authors: Seidlits Stephanie K. , Schmidt Christine E. , Shear Jason B. 
Published: October 2009

AbstractThe development of three‐dimensional, spatially defined neuronal cultures that mimic chemical and physical attributes of native tissue is of considerable interest for various applications, including the development of tailored neuronal networks and clinical repair of damaged nerves. Here, the use of multiphoton excitation to photocrosslink protein microstructures within three‐dimensional, optically transparent hydrogel materials, such as those based on hyaluronic acid, is reported. Multiphoton excitation confines photocrosslinking to a three‐dimensional voxel with submicron spatial resolution, enabling fabrication of protein matrices with low‐ to sub‐micrometer feature sizes by scanning the focus of a laser relative to the reagent solution. These methods can be used to create complex three‐dimensional architectures that provide both chemical and topographical cues for cell culture and guidance, providing for the first time a means to direct cell adhesion and migration on size scales relevant to in vivo environments. Using this approach, guidance of both dorsal root ganglion cells (DRGs) and hippocampal neural progenitor cells (NPCs) along arbitrary, three‐dimensional paths is demonstrated.
Gonadal steroids and salivary IgA in healthy young women and men
Authors: Van Anders Sari M. 
Published: October 2009

AbstractEmpirical evidence from clinical, nonhuman animal, and in vitro studies point to links between immune function and gonadal steroids, including potential androgenic immunosuppression and estrogenic immunoenhancement. This study was designed to test links between steroids and one marker of mucosal humoral immunity—immunoglobulin A (IgA) in healthy individuals, to facilitate comparisons with other species and clinical populations, as there are few existing studies with healthy humans that also allow gender/sex investigations. Participants (86 women, 91 men) provided a saliva sample for measurement of testosterone (T), estradiol (E2), and IgA. Results showed that E2 was significantly and positively correlated with IgA in women, and group analyses by E2 quartile showed that this association was linear. No significant correlations or nonlinear associations were seen between T and IgA in men or women, or E2 and IgA in men. Evidence from this study indicates that IgA and E2 are significantly associated in healthy premenopausal women. Am. J. Hum. Biol. 2010. © 2009 Wiley‐Liss, Inc.
Vanadium(V)/mandelic acid initiated graft copolymerization of acrylamide onto guar gum in an aqueous medium
Authors: Srivastava Arti , Mishra Vivek , Singh Shailendra Kumar , Kumar Rajesh 
Published: October 2009

AbstractThe graft copolymerization reaction of acrylamide onto guar gum with a vanadium(V)/mandelic acid redox pair was carried out in an N2 atmosphere. The optimum concentrations of vanadium(V), mandelic acid, hydrogen ions, acrylamide, and guar gum for the maximum percentage of grafting were 6.0 × 10−3, 2.0 × 10−2, 55.0 × 10−2, and 20.0 × 10−2 mol/dm3 and 110.1 × 10−2 g/dm3, respectively. The optimum time and temperature of reaction were 90 min and 35°C, respectively, and during the study of [H+] variation, a prompt change in the value of the grafting parameters was observed. The maximum percentage of swelling of the graft copolymer was achieved at room temperature in 1 h. Studies of the flocculation, viscosity, and metal‐ion absorption capacity were also performed. The synthesized graft copolymer was characterized by Fourier transform infrared spectroscopy and thermogravimetric analyses, which showed that the grafted guar gum was thermally more stable than the ungrafted guar gum. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Online monitoring of the thermal degradation of POM during melt extrusion
Authors: Rajan Vipin V. , Wäber Roy , Wieser Jürgen 
Published: October 2009

AbstractBecause of its high stiffness, chemical resistance, and low viscosity, Poly (oxymethylene) (POM) is of high relevance for technical applications. The thermal degradation of POM during processing affects its final properties and decreases the long‐term stability. The degradation is indicated by the emission of formaldehyde (FA) gas. The aim of this study is to monitor the thermal degradation of POM online, during the melt extrusion in a co‐rotating twin screw extruder (TSE). The effect of the processing conditions on the thermal stabilisation of the POM is observed by FA emission and online viscosity measurements. The effect of processing conditions on the compounding of POM with two different FA scavengers is also studied. Fourier transform infrared (FTIR) spectroscopy is used for the online measurement of FA gas and acetyl acetone colour measurement for the offline characterisation. The online viscosity is measured by passing the melt through a slit die at constant volume flow rate. An enhanced thermal degradation is found with decreasing throughput and increasing screw speed. A good correlation between the online viscosity and offline FA measurement is observed. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010