bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design of Clinical Trials in Acute Kidney Injury
Authors: Palevsky Paul M. , Molitoris Bruce A. , Okusa Mark D. , Levin Adeera , Waikar Sushrut S. , Wald Ron , Chertow Glenn M. , Murray Patrick T. , Parikh Chirag R. , Shaw Andrew D. , Go Alan S. , Faubel Sarah G. , Kellum John A. , Chinchilli Vernon M. , Liu Kathleen D. , Cheung Alfred K. , Weisbord Steven D. , Chawla Lakhmir S. , Kaufman James S. , Devarajan Prasad , Toto Robert M. , Hsu Chi-yuan , Greene Tom , Mehta Ravindra L. , Stokes John B. , Thompson Aliza M. , Thompson B. Taylor , Westenfelder Christof S. , Tumlin James A. , Warnock David G. , Shah Sudhir V. , Xie Yining , Duggan Emily G. , Kimmel Paul L. , Star Robert A. 
Published: March 2012

Summary
Acute kidney injury (AKI) remains a complex clinical problem associated with significant short-term morbidity and mortality and lacking effective pharmacologic interventions. Patients with AKI experience longer-term risks for progressive chronic ESRD, which diminish patients’ health-related quality of life and create a larger burden on the healthcare system. Although experimental models have yielded numerous promising agents, translation into clinical practice has been unsuccessful, possibly because of issues in clinical trial design, such as delayed drug administration, masking of therapeutic benefit by adverse events, and inadequate sample size. To address issues of clinical trial design, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored a workshop titled “Clinical Trials in Acute Kidney Injury: Current Opportunities and Barriers” in December 2010. Workshop participants included representatives from academia, industry, and government agencies whose areas of expertise spanned basic science, clinical nephrology, critical care medicine, biostatistics, pharmacology, and drug development. This document summarizes the discussions of collaborative workgroups that addressed issues related to patient selection, study endpoints, the role of novel biomarkers, sample size and power calculations, and adverse events and pilot/feasibility studies in prevention and treatment of AKI. Companion articles outline the discussions of workgroups for model trials related to prevention or treatment of established AKI in different clinical settings, such as in patients with sepsis.
Effects of Dapagliflozin, an SGLT2 Inhibitor, on HbA1c, Body Weight, and Hypoglycemia Risk in Patients With Type 2 Diabetes Inadequately Controlled on Pioglitazone Monotherapy
Authors: Rosenstock Julio , Vico Marisa , Wei Li , Salsali Afshin , List James F. 
Published: March 2012

OBJECTIVE
To examine the safety and efficacy of dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, added on to pioglitazone in type 2 diabetes inadequately controlled on pioglitazone.

RESEARCH DESIGN AND METHODS
Treatment-naive patients or those receiving metformin, sulfonylurea, or thiazolidinedione entered a 10-week pioglitazone dose-optimization period with only pioglitazone. They were then randomized, along with patients previously receiving pioglitazone ≥30 mg, to 48 weeks of double-blind dapagliflozin 5 (n = 141) or 10 mg (n = 140) or placebo (n = 139) every day plus open-label pioglitazone. The primary objective compared HbA1c change from baseline with dapagliflozin plus pioglitazone versus placebo plus pioglitazone at week 24. Primary analysis was based on ANCOVA model using last observation carried forward; all remaining analyses used repeated-measures analysis.

RESULTS
At week 24, the mean reduction from baseline in HbA1c was −0.42% for placebo versus −0.82 and −0.97% for dapagliflozin 5 and 10 mg groups, respectively (P = 0.0007 and P &lt; 0.0001 versus placebo). Patients receiving pioglitazone alone had greater weight gain (3 kg) than those receiving dapagliflozin plus pioglitazone (0.7–1.4 kg) at week 48. Through 48 weeks: hypoglycemia was rare; more events suggestive of genital infection were reported with dapagliflozin (8.6–9.2%) than placebo (2.9%); events suggestive of urinary tract infection showed no clear drug effect (5.0–8.5% for dapagliflozin and 7.9% for placebo); dapagliflozin plus pioglitazone groups had less edema (2.1–4.3%) compared with placebo plus pioglitazone (6.5%); and congestive heart failure and fractures were rare.

CONCLUSIONS
In patients with type 2 diabetes inadequately controlled on pioglitazone, the addition of dapagliflozin further reduced HbA1c levels and mitigated the pioglitazone-related weight gain without increasing hypoglycemia risk.
Toward the Optimal dose Metric in Continuous Renal Replacement Therapy
Authors: Granado Rolando Claure-Del , Macedo Etienne , Chertow Glenn M. , Soroko Sharon , Himmelfarb Jonathan , Ikizler T. Alp , Paganini Emil P. , Mehta Ravindra L. 
Published: March 2012

Purpose: There is no consensus on the optimal method to measure delivered dialysis dose in patients with acute kidney injury (AKI). The use of direct dialysate-side quantification of dose in preference to the use of formal blood-based urea kinetic modeling and simplified blood urea nitrogen (BUN) methods has been recommended for dose assessment in critically-ill patients with AKI. We evaluate six different blood-side and dialysate-side methods for dose quantification. Methods: We examined data from 52 critically-ill patients with AKI requiring dialysis. All patients were treated with pre-dilution CVVHDF and regional citrate anticoagulation. Delivered dose was calculated using blood-side and dialysis-side kinetics. Filter function was assessed during the entire course of therapy by calculating BUN to dialysis fluid urea nitrogen (FUN) ratios q/12 hours. Results: Median daily treatment time was 1,413 min (1,260–1,440). The median observed effluent volume per treatment was 2,355 mL/h (2,060–2,863) (p<0.001). Urea mass removal rate was 13.0±7.6 mg/min. Both EKR (r2=0.250; p<0.001) and KD (r2=0.409; p<0.001) showed a good correlation with actual solute removal. EKR and KD presented a decline in their values that was related to the decrease in filter function assessed by the FUN/BUN ratio. Conclusions: Effluent rate (mL/kg/h) can only empirically provide an estimated of dose in CRRT. For clinical practice, we recommend that the delivered dose should be measured and expressed as KD. EKR also constitutes a good method for dose comparisons over time and across modalities.
The prognostic significance of lymphopenia in peripheral T‐cell and natural killer/T‐cell lymphomas: A study of 826 cases from the International Peripheral T‐cell Lymphoma Project
Authors: Mitrovic Zdravko , Perry Anamarija M. , Suzumiya Junji , Armitage James O. , Au Wing Y. , Coiffier Bertrand , Holte Harald , Jaffe Elaine S. , Monserrat Emili , Rajan Sandeep K. , Savage Kerry J. , Tobinai Kensei , Vose Julie M. , Weisenburger Dennis D. 
Published: March 2012

AbstractLymphopenia is a marker of inferior survival in patients with various malignancies. However, the prognostic significance of lymphopenia in peripheral T‐cell lymphoma (PTCL) is unclear. We analyzed the prognostic significance of lymphopenia in 826 patients with different types of PTCL and natural killer/T‐cell lymphoma (NKTCL) from the International Peripheral T‐cell Lymphoma Project. Lymphopenia was defined as an absolute lymphocyte count of less than 1,000 cells per microliter. The overall frequency of lymphopenia was 35.3%, ranging from 21.1% in ALK+anaplastic large cell lymphoma (ALCL) to 47.5% in angioimmunoblastic T‐cell lymphoma (AITL). Lymphopenia was independently associated with an inferior overall survival (OS) in patients with the lymphoma type of adult T‐cell leukemia/lymphoma (ATLL), with a 2‐year OS of 15% versus 40% for those without lymphopenia (P< 0.001). Lymphopenia was also an adverse predictor of survival in PTCL, not otherwise specified, but was associated with other unfavorable prognostic factors. A trend toward inferior survival for lymphopenic patients was also observed in AITL, ALK−ALCL and extranasal NKTCL lymphoma, whereas no difference in survival was found in nasal NKTCL, ALK+ALCL, or enteropathy‐associated T‐cell lymphoma. In this study, lymphopenia was identified as a new adverse prognostic factor in the lymphoma type of ATLL. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.
Evaluation of hemostasis in flowing blood
Authors: Grabowski Eric F. , Yam Kylee , Gerace Matthew 
Published: March 2012

AbstractHemostasis and thrombosis are now increasingly recognized as integrally related to blood rheology and blood flow. Platelets, for example, are known to access the vessel wall in ways which depend upon the small‐scale motions of neighboring erythrocytes, and access one another via collisions driven by gradients in blood flow velocity. In this context, flow devices have become a subject of great interest in the clinical assessment of bleeding disorders, especially platelet function defects and von Willebrand disease. While these devices currently lack standardization and outcomes measures which establish clear clinical utility, their promise remains great, particularly in the potential to simulate the microenvironment of arteries vs. veins and in their ability to incorporate such intrinsically flow‐dependent phenomena as co‐localization of tissue‐factor‐bearing microparticles with platelets, the weakness of the GPIb‐vWF bond at very high shear stresses, and even the hemostatic and antithrombotic function of vascular endothelium. In contrast, currently utilized assays are often performed under static conditions that do not involve flow and therefore are not able to simulate the microenvironment of arteries and veins. Am. J. Hematol., 2012. © 2012 Wiley Periodicals, Inc.
A comparison of attrition rates in patients undergoing sublingual immunotherapy vs subcutaneous immunotherapy
Authors: Hsu Nicole M. , Reisacher William R. 
Published: March 2012

AbstractBackground:Effective allergy immunotherapy (IT) requires patient compliance. Numerous studies have shown high noncompliance rates in patients undergoing IT. For patients enrolled in subcutaneous IT (SCIT), noncompliance rates were noted to range from 11% to 50%, whereas sublingual IT (SLIT) patients had noncompliance rates ranging from 3% to 25%. Comparing noncompliance rates is difficult because noncompliance in SCIT is defined as withdrawal from therapy, whereas in SLIT it is considered poor adherence to daily administration. The aim of this study was to compare attrition rates in patients enrolled in SCIT vs SLIT, as well as major factors leading to termination of IT.Methods:We retrospectively compared attrition rates, IT duration, and reasons for termination between patients enrolled in SCIT (n = 139) and SLIT (n = 78), over a 4‐year period.Results:Attrition rates for SCIT and SLIT were 45% and 41%, respectively (p = 0.669). No significant difference in duration of IT was observed between the groups (≤1 month, p = 0.079; 1‐2 months, p = 0.486; 2‐3 months, p = 0.165; 3‐6 months, p = 0.575; 6‐12 months, p = 0.361; 12–24 months, p = 1.000; and ≥24 months, p = 0.258). Among reasons cited for discontinuing IT, SCIT patients reported inconvenience (p = 0.001), whereas SLIT patients indicated efficacy concerns (p = 0.022) as the major basis for withdrawal.Conclusion:No significant difference was observed in attrition rates between SCIT and SLIT. While there was no significant difference in duration of IT prior to withdrawal, there was a trend toward earlier withdrawal in SCIT patients. The reasons for withdrawal, however, were considerably different between the 2 groups. © 2012 ARS‐AAOA, LLC.
Surface coating on cotton fabrics of new multilayer formulations based on superabsorbent hydrogels synthesized by gamma radiation designed for diapers
Authors: Nizam El‐Din Horia M. 
Published: March 2012

AbstractIn this work, superabsorbent formulations composed of two layers of hydrogels, prepared by gamma irradiation, were surface coated on cotton fabrics. The first layer, which is directly surface coated on cotton fabrics, was based on the copolymer hydrogel of 2‐acrylamido‐2‐methylpropanesulfonic acid/2‐dimethyaminoethyl methacrylate (AMPS/DEMA). The top layer was based on pure AMPS hydrogel. The different hydrogel layers were characterized in terms of thermal stability by thermogravimetric analysis and mechanical testing. In addition, the swelling of the different layers of hydrogels in water and urea solutions (as a solution resembling urine) were studied. The results showed that the multilayer hydrogels obtained displayed higher swelling in urea than in water, which is promising in the field of diapers. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Learning surgically oriented anatomy in a student‐run extracurricular club: An education through recreation initiative
Authors: Ullah Shahnoor M. , Bodrogi Andrew , Cristea Octav , Johnson Marjorie , McAlister Vivian C. 
Published: March 2012

AbstractDidactic and laboratory anatomical education have seen significant reductions in the medical school curriculum due, in part, to the current shift from basic science to more clinically based teaching in North American medical schools. In order to increase medical student exposure to anatomy, with clinical applicability, a student‐run initiative called surgically oriented anatomy prosectors (SOAP) club was created within the extracurricular program at the Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Canada. SOAP invites surgeons and residents from various surgical specialties to demonstrate, on a cadaver, a surgical procedure of their choosing. During the demonstration, the anatomy, as it relates to the surgical procedure, is discussed. The students then break into smaller groups to examine the relevant anatomy on the cadavers, during which time the discussion is broadened. The group continues the conversation in a social environment with refreshments. SOAP is one of the most popular extracurricular clubs with 65% of first and second year medical students registered as members. The high demand for SOAP, along with the positive participant feedback, may be due to its utilization of the principle of education through recreation, which seeks to provide opportunities for learning seamlessly throughout all facets of life. It also demonstrates the desire, amongst certain medical students, to learn applied anatomy, particularly within a surgical context. Anat Sci Educ. © 2012 American Association of Anatomists.
Safety modeling for two‐way left‐turn lanes and a procedure to identify two‐way left‐turn lane segments with safety concerns
Authors: Lu Jian John , Chen Shengdi , Pernia Juan C. , Lu Linjun 
Published: March 2012

SUMMARYIn the past, two‐way left‐turn lane (TWLTL) median treatments have been frequently used in Florida to inexpensively improve traffic and safety performances. In order to identify factors that may have significant impacts on safety operations in TWLTL sections and to identify TWLTL locations that present existing and future safety concerns, a research project was carried out and results are summarized in the paper. In the research, a three‐year crash history database with crashes and section characteristics from a total of 1688 TWLTL sections all over Florida was developed and used. A negative binomial regression model was developed to determine the statistical relationship between the number of crashes per mile per year and several variables such as traffic volume, access density, posted speed, and number of lanes. In regard to the methodology, in order to identify locations with safety concerns, several steps are needed: development of real crash data distribution, determination of statistical distribution models that better represent the actual crash data, determination of percentile values for the average number of crashes, estimation of crash rates for sections with the same characteristics, estimation of critical values for the variables corresponding to the percentile values for average number of crashes, calculation of tables of critical average annual daily traffic values, and generation of a list of TWLTL locations with critical safety concerns. Results presented in the paper have been used in real applications. Copyright © 2012 John Wiley & Sons, Ltd.
Impact of CO2 Emission Variation on Firm Performance
Authors: Alvarez Isabel Gallego 
Published: March 2012

ABSTRACTThe quantifying and reporting of greenhouse gas emissions is one of the most important tools for monitoring and auditing proposed to mitigate climate change, and it also directly affects business. It is thus vital that at this time we learn in detail whether firms actually report on greenhouse gas emissions and make the account entries that must be included within it.This research is twofold: first to analyse the reports on greenhouse gas emissions of international firms in the 2007 and 2008 period and to see what kind of variation occurs in CO2 emissions between 2006–2007 and 2007–2008, and second to determine the impact that this variation (2006–2007) can have on firm performance in four time periods (t, t + 1, t + 2 and t + 3) that correspond to 2007, 2008, 2009 and 2010, taking two variables as a measure of firm performance, ROE and ROA, and considering a time period affected by a financial crisis.The results obtained show that there was a reduction in CO2 emissions in the 2006–2007 period, and also in the 2007–2008 period. As regards the impact that the variation in CO2 emissions has on ROE and ROA, CO2 emission variation is a significant but negative variable only for ROA_2007 and for the rest of the years it is not statistically significant either for ROE or ROA. Copyright © 2012 John Wiley & Sons, Ltd and ERP Environment.
Enhancing the Efficiency of Directed Evolution in Focused Enzyme Libraries by the Adaptive Substituent Reordering Algorithm
Authors: Feng Xiaojiang , Sanchis Joaquin , Reetz Manfred T. , Rabitz Herschel 
Published: March 2012

AbstractDirected evolution is a broadly successful strategy for protein engineering in the quest to enhance the stereoselectivity, activity, and thermostability of enzymes. To increase the efficiency of directed evolution based on iterative saturation mutagenesis, the adaptive substituent reordering algorithm (ASRA) is introduced here as an alternative to traditional quantitative structure–activity relationship (QSAR) methods for identifying potential protein mutants with desired properties from minimal sampling of focused libraries. The operation of ASRA depends on identifying the underlying regularity of the protein property landscape, allowing it to make predictions without explicit knowledge of the structure–property relationships. In a proof‐of‐principle study, ASRA identified all or most of the best enantioselective mutants among the synthesized epoxide hydrolase from Aspergillus niger, in the absence of peptide seeds with high E‐values. ASRA even revealed a laboratory error from irregularities of the reordered E‐value landscape alone.
Multi‐Criteria Aspects of Modularization in the Process Plant Layout and Design
Authors: Hady Łukasz , Wozny Günter 
Published: March 2012

AbstractEine breite Anwendung der Modularisierung bei der Planung verfahrenstechnischer Anlagen ist bisher vor allem durch fehlende einheitliche und von allen akzeptierte modulare Strukturen sowie Ansätze begrenzt. Neben den bestehenden Ansätzen zur Modularisierung verfahrenstechnischer Anlagen wird ein Modularisierungskonzept dargestellt, mit dem verschiedene Aspekte der Modularisierung gleichzeitig bei der Anlagenplanung berücksichtigt werden können. Das modulare Konzept umfasst hierbei die Definition und Identifizierung von Modulen, deren dreidimensionales Design, die Ablage und Know‐how‐Sicherung zwecks der Wiederverwendung des Engineering und der Ausrüstungen sowie die Planung und Kostenschätzung mit wiederverwendbaren Modulen. Abschließend wird die Modularisierung von Miniplant‐Anlagen sowie die Einführung der Modularisierung in die Lehre vorgestellt.
The minute brain of the copepod Tigriopus californicus supports a complex ancestral ground pattern of the tetraconate cerebral nervous systems
Authors: Andrew David R. , Brown Sheena M. , Strausfeld Nicholas J. 
Published: March 2012

AbstractCopepods are a diverse and ecologically crucial group of minute crustaceans that are relatively neglected in terms of studies on nervous system organization. Recently, morphological neural characters have helped clarify evolutionary relationships within Arthropoda, particularly among Tetraconata (i.e., crustaceans and hexapods), and indicate that copepods occupy an important phylogenetic position relating to both Malacostraca and Hexapoda. This taxon therefore provides the opportunity to evaluate those neural characters common to these two clades likely to be results of shared ancestry (homology) versus convergence (homoplasy). Here we present an anatomical characterization of the brain and central nervous system of the well‐studied harpacticoid copepod species Tigriopus californicus. We show that this species is endowed with a complex brain possessing a central complex comprising a protocerebral bridge and central body. Deutocerebral glomeruli are supplied by the antennular nerves, and a lateral protocerebral olfactory neuropil corresponds to the malacostracan hemiellipsoid body. Glomeruli contain synaptic specializations comparable to the presynaptic “T‐bars” typical of dipterous insects, including Drosophila melanogaster. Serotonin‐like immunoreactivity pervades the brain and ventral nervous system, with distinctive deutocerebral distributions. The present observations suggest that a suite of morphological characters typifying the Tigriopus brain reflect a ground pattern organization of an ancestral Tetraconata, which possessed an elaborate and structurally differentiated nervous system. J. Comp. Neurol. 520:3446–3470, 2012. © 2012 Wiley Periodicals, Inc.
Organization of the gymnotiform fish pallium in relation to learning and memory: IV. Expression of conserved transcription factors and implications for the evolution of dorsal telencephalon
Authors: Harvey‐Girard Erik , Giassi Ana C.C. , Ellis William , Maler Leonard 
Published: March 2012

AbstractWe have cloned the apteronotid homologs of FoxP2, Otx1, and FoxO3. There was, in the case of all three genes, good similarity between the apteronotid and human amino acid sequences: FoxP2, 78%; Otx1, 54%; FoxO3, 71%. The functional domains of these genes were conserved to a far greater extent, on average: FoxP2, 89%; Otx1, 76%; FoxO3, 82%. This led us to hypothesize that the cellular functions of these genes might also be conserved. We used in situ hybridization to examine the distribution of the mRNA transcripts of these genes in the apteronotid telencephalon. We confined our analysis to the pallial regions previously associated with learning about social signals, whose circuitry has been closely examined in the other articles of this series. We found that AptFoxP2 and AptOtx1 transcripts were expressed predominantly in the dorsocentral division of the pallium (DC); the dorsolateral division of the pallium (DL) contained only weakly labeled neurons. In both cases, the distribution of labeled neurons was very heterogeneous, and unlabeled neurons could be found adjacent to strongly labeled ones. In contrast, we found that most neurons in DL strongly expressed AptFoxO3 mRNA, although there was only weak expression in a small number of cells within DC. We briefly discuss the relevance of our results regarding the functional roles of AptFoxP2/AptOtx1‐expressing neurons in DC for communication vs. foraging behavior. We extensively discuss the implications of our results for possible homologies between DL and DC and medial and dorsal pallium of tetrapods, respectively. J. Comp. Neurol. 520:3395–3413, 2012. © 2012 Wiley Periodicals, Inc.