bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of everolimus in patients with metastatic insulinoma and refractory hypoglycemia
Authors: Bernard Valérie , Lombard-Bohas Catherine , Taquet Marie-Caroline , Caroli-Bosc François-Xavier , Ruszniewski Philippe , Niccoli Patricia , Guimbaud Rosine , Chougnet Cécile N , Goichot Bernard , Rohmer Vincent , Borson-Chazot Françoise , Baudin Eric , _ _ 
Published: February 2013

BackgroundRefractory hypoglycemia in patients with metastatic insulinoma is an important cause of morbidity and mortality. Everolimus could be a new therapeutic option.MethodsWithin the French Group, we conducted a retrospective, multicentric study of endocrine tumors to evaluate the time to the first recurrence of symptomatic hypoglycemia, after everolimus initiation, in patients with metastatic insulinoma and refractory hypoglycemia. Ongoing hyperglycemic medical options, tumor response, and safety information were recorded.ResultsTwelve patients with metastatic insulinoma and refractory hypoglycemia who were treated with everolimus between May 2007 and June 2011 were reviewed. Everolimus (starting dose, 10 mg/day, except in one patient, 5 mg/day) was given after a median of four previous therapeutic lines. Medication aimed at normalizing blood glucose levels in 11 patients. After a median duration of 6.5 months (range 1–35+ months), median time to the first recurrence of symptomatic hypoglycemia was 6.5 months (range 0 to 35+ months). Three patients discontinued everolimus because of cardiac and/or pulmonary adverse events at 1, 1.5, and 7 months after initiation, which led to two deaths. Three patients discontinued everolimus because of tumor progression at 2, 3, and 10 months after initiation, without recurrence of hypoglycemia.ConclusionEverolimus appears to be a new effective treatment for patients with metastatic insulinoma and refractory hypoglycemia. Tolerance should be carefully monitored.
Secretory Protein Biogenesis and Traffic in the Early Secretory Pathway
Authors: Barlowe Charles K , Miller Elizabeth A 
Published: February 2013

Abstract
The secretory pathway is responsible for the synthesis, folding, and delivery of a diverse array of cellular proteins. Secretory protein synthesis begins in the endoplasmic reticulum (ER), which is charged with the tasks of correctly integrating nascent proteins and ensuring correct post-translational modification and folding. Once ready for forward traffic, proteins are captured into ER-derived transport vesicles that form through the action of the COPII coat. COPII-coated vesicles are delivered to the early Golgi via distinct tethering and fusion machineries. Escaped ER residents and other cycling transport machinery components are returned to the ER via COPI-coated vesicles, which undergo similar tethering and fusion reactions. Ultimately, organelle structure, function, and cell homeostasis are maintained by modulating protein and lipid flux through the early secretory pathway. In the last decade, structural and mechanistic studies have added greatly to the strong foundation of yeast genetics on which this field was built. Here we discuss the key players that mediate secretory protein biogenesis and trafficking, highlighting recent advances that have deepened our understanding of the complexity of this conserved and essential process.
The Genetics of Canine Skull Shape Variation
Authors: Schoenebeck Jeffrey J , Ostrander Elaine A 
Published: February 2013

AbstractA dog’s craniofacial diversity is the result of continual human intervention in natural selection, a process that began tens of thousands of years ago. To date, we know little of the genetic underpinnings and developmental mechanisms that make dog skulls so morphologically plastic. In this Perspectives, we discuss the origins of dog skull shapes in terms of history and biology and highlight recent advances in understanding the genetics of canine skull shapes. Of particular interest are those molecular genetic changes that are associated with the development of distinct breeds.
Θ CuAl2 Precipitate Coarsening in Al-2% Cu Thin Films
Authors: Sanchez John E. , McKnelly L. T. , Morris J. W. 
Published: February 2013

AbstractΘ phase CuAl2 precipitate size evolution during coarsening at 310°C in 0.5 μm thick Al-2% (wt) Cu thin films was characterized by transmission electron microscopy. Films were sputter deposited onto oxidized Si substrates by standard techniques. The coarsening process preferred the growth of blocky Θ morphologies at Al triple points. Coarsening was via solute Cu diffusion along Al grain boundaries during annealing. The average Θ size dependence on annealing time (t) is approximately (t)1/4 in general agreement with models for particle coarsening along grain boundaries. Concurrent Al grain growth was shown to initially enhance the Θ coarsening rate above (t)1/4 behavior. This boundary coarsening process leads to a grain size dependence of the coarsening rate which has been observed in related and other previous work in thin films. These results are shown to be relevant for effects produced during accelerated electromigration testing, such as previous ‘curious’ 0 morphologies at triple points observed by others, the enhanced flux of Cu during testing, and possible mechanisms affecting electromigration failure processes.
Void Elongation Phenomena Observed in Polycrystalline Cu Interconnects at a High Current Density Stressing Conditions
Authors: Shingubara S. , Kajiwara S. , Osaka T. , Sakaue H. , Takahagi T. 
Published: February 2013

ABSTRACTFormation and morphological change of voids induced by electromigration in polycrystalline Cu interconnects on TiN have been investigated at various current density conditions at elevated temperatures. At first voids were formed at grain boundaries, then they grew further to elongate in the electric field direction. Void elongation parameter (a ratio of void diameters in longitudinal to lateral directions to the electric field) was 2.53 when the current density was 9×106A/cm2, while it was 1.31 when the current density was 3×106A/cm2at 400°C, 50h. Occurrence of void elongation is enhanced with increase in current density, and its relationship to grain boundaries are discussed by FIB-SIM image analysis.
Effects of Nitrogen on Preventing the Crystallization of Amorphous Ta-Si-N Diffusion Barrier
Authors: Kim Dong Joon , Jeon Soon Pil , Kim Yong Tae , Park Jong-Wan 
Published: February 2013

ABSTRACTAmorphous Ta-Si-N thin film was deposited by dc sputterring of Ta5Si3 target in (Ar+N2) atmosphere. The crystal structure and the thermal stability of Ta-Si-N thin films were investigated by XRD, RBS, AES, Nomarski microscope, and TEM. When the concentration of nitrogen in Ta-Si-N thin film was higher than 40 at.%, the Ta-Si-N thin film remained the amorphous state after the annealing at 1100°C for 60 min. In this case, the Cu diffusion was prevented by the amorphous Ta-Si-N thin film even if the annealing temperature increased up to 900°C for 30 min. Whereas, the Ta-Si-N thin film with nitrogen concentration less than 40 at. % was transformed from the amorphous to the polycrystalline TaSi2 phases after the annealing at 900°C for 60 min and failed to prevent the Cu diffusion after the annealing at 700°C for 30 min.
Three-Dimensional Finite Element Simulation of Electro and Stress Migration Effects in Interconnect Lines
Authors: Rzepka Sven , Korhonen Matt A. , Weber Eicke R. , Li Che-Yu 
Published: February 2013

ABSTRACTA tool for 3-D modeling of EM and SM in interconnect lines has been developed based on a commercial finite element code. After detailing the approach, we focus on the verification of the simulator by comparing the results of 1-D analytic and FEM simulations, and then we apply the simulator to interconnect line segments with a specified grain structure.
Thermoelectric properties of Tl9BiTe6 / Tl9BiSe6 solid solutions
Authors: Wölfing Bernd , Kloc Christian , Bucher Ernst 
Published: February 2013

ABSTRACTThe compounds Tl9BiTe6 (TBT) and Tl9BiSe6 (TBS) crystallize in the tetragonal space group I4/mcm. Tl9BiTe6 has a thermopower of 185 μV/K and an electrical resistivity of 5.5 mΩcm at 300K, resulting in a power factor of S2/ρ = 0.6 mW/mK2. Compared to Bi2Te3 which is the state of the art material at this temperature this is about a factor of 7 lower. At 300 K TBS has a thermopower of 750 μV/K but a high resistivity of 130 Ωcm. To optimize the thermoelectric properties of TBT solid solutions have been formed with TBS. The resistivities and have been measured on Tl9BiTe1-xSex with x = 0.05, 0.08, 0.2 and 0.5. In addition to the electrical properties the lattice constants have been measured by X-ray diffraction. The dependence of the lattice constants on the Te/Se ratio clearly deviates from Vegard's law. Different affinities of Te and Se towards the two chalcogenide sites in the crystal can explain this behavior.
Association and Mutation Analyses of the IRF6 Gene in Families with Nonsyndromic and Syndromic Cleft Lip and/or Cleft Palate
Authors: Pegelow M. , Koillinen H. , Magnusson M. , Fransson I. , Unneberg P. , Kere J. , Karsten A. , Peyrard-Janvid M. 
Published: February 2013

Objectives (1) To detect interferon regulatory factor 6 gene ( IRF6) mutations in newly recruited Van der Woude syndrome (VWS) and popliteal pterygium syndrome (PPS) families. (2) To test for association, in nonsyndromic cleft lip and/or cleft palate (NSCL/P) and in VWS/PPS families, the single nucleotide polymorphism (SNP) rs642961, from the IRF6 enhancer AP-2α region, alone or as haplotype with rs2235371, a coding SNP (Val274Ile). Design IRF6 mutation screening was performed by direct sequencing and genotyping of rs642961 and rs2235371 by TaqMan technology. Patients Seventy-one Swedish NSCL/P families, 24 Finnish cleft palate (CP) families, and 24 VWS/PPS families (seven newly recruited) were studied. Results Allelic and genotypic frequencies in each phenotype were compared to those of the controls, and no significant difference could be observed. IRF6 gene mutation was detected in six of the seven new VWS/PPS families. Association analysis of the entire VWS/PPS sample set revealed the A allele from rs642961 to be a risk allele. Significant association was detected in the Swedish CP subset of our NSCL/P collection where the G-C haplotype for rs642961-rs2235371 were at risk ( P= .013). Conclusions Our results do not support the previously reported association between the A allele of rs642961 and the NSCL phenotype. However, in the VWS/PPS families, the A allele was a risk allele and was, in a large majority (>80%), transmitted on the same chromosome as the IRF6 mutation.
Developing a Measure of Appraisal: A Psychometric Analysis of the Parental Appraisal of Cleft Questionnaire
Authors: Shuttlewood Emma , Dalton Louise , Cooper Myra 
Published: February 2013

Objective To develop a questionnaire measure of appraisals for parents of children with a cleft (the Parental Appraisal of Cleft Questionnaire) and to investigate the ability of the Parental Appraisal of Cleft Questionnaire to predict variance in parental well-being. Design, Participants, Setting The study used a cross-sectional postal and online questionnaire design with a retest component involving parents of children with a cleft lip and/or palate. Data are presented for 179 parents, predominantly women (74.9%), aged 22 to 58 years. Main Outcome Measures Participants completed the appraisal measure under development; other measures of psychological well-being, social support, and socially desirable responding; and demographic information. Results Overall, the Parental Appraisal of Cleft Questionnaire was found to have a coherent factor structure, good internal reliability, and good test-retest reliability. The Parental Appraisal of Cleft Questionnaire was also found to predict a significant amount of unique variance in well-being over and above the variance predicted by demographic, social support, and social desirability variables. Conclusions Parental appraisals, measured by the Parental Appraisal of Cleft Questionnaire, were found to predict unique variance in well-being. These findings are discussed in relation to adjustment to cleft lip and/or palate for parents. Directions for future research are outlined and the implications for clinical practice and services are discussed.
Selecting Candidate Wells for Refracturing Using Production Data
Authors: Roussel Nicolas P. , Sharma Mukul M. 
Published: February 2013

Summary
The selection of candidate wells for refracturing is often very difficult to peform based on the information available at the surface. We propose a systematic methodology to allow a field engineer to evaluate a well's potential for refracturing from an analysis of field-production data and other reservoir data commonly available. The well-selection method was successfully confronted to a case study in the Wattenberg field using data from 300 Codell tight gas wells.
The performance of refracturing treatments has been observed to be highly variable in the Wattenberg field (Colorado), with some wells underperforming while others are restored to initial or even higher production rates. Historically, multiple approaches have been taken to select the best candidate wells, including heuristic guidelines, field correlations, and neural networks.
After identifying the physical phenomena that are thought to impact the performance of refracturing operations, five dimensionless groups were developed to quantify them. By choosing a dimensionless approach, the goal is to establish refracturing criteria that will not limited to one specific field, but may used in distinct oil and gas fields. One potential motivation for refracturing is the stress reorientation occurring around a fractured well, causing the refracture to propagate orthogonally to the initial fracture in underdepleted sections of the reservoir. Numerical simulations of the areal extent of the stress-reversal region as well as tiltmeter measurements confirmed the existence of refracture reorientation in the Codell formation. Guidelines for the selection of refracturing candidates were expressed in terms of the potential for stress reorientation, the quality of the initial completion, the initial production decline, and the reservoir depletion around the well of interest. Two groups of wells showed the most promise for refracturing: (a) ineffective initial completions with a small initial production decline and (b) long initial fractures in underdepleted reservoirs. The dimensionless groups help us identify such wells and provide quantitative criteria for selection of wells that may be good candidates for refracturing.
“Squimulation”—Simultaneous Well-Stimulation and Scale-Squeeze Treatments in Deepwater West Africa
Authors: Patterson D. , Kendrick M. , Williams W. , Jordan M. 
Published: February 2013

SummaryIn a deepwater west African field, the relatively small number of high-cost, highly productive wells, coupled with a high barium sulfate scaling tendency (upon waterflood breakthrough of injected seawater) requires effective scale management along with removal of near-wellbore damage in order to achieve high hydrocarbon recovery.The nature of the well-completion strategy in the field (frac packs for sand control) had resulted in some wells with higher than expected skin values owing to drilling-fluid losses, residual fracture gel, fluid loss agents, and fines mobilization within the frac packs.The paper will present how the challenges of managing impaired completions and inorganic scale forced innovation in terms of when to apply both stimulation and scale-inhibitor packages to deepwater wells. This paper will outline a novel process for non-conventional batch chemical applications where bullhead stimulation treatments have been displaced deep into the formation (&gt;20 ft) using a scale inhibitor overflush. Not only does this benefit the stimulation by displacing the spent acid and reagents away from the immediate wellbore area, but the combined treatment provides a cost savings with a single mobilization for the combined treatment. The paper will describe the laboratory testing that was performed to qualify the treatments. The four field treatments that were performed demonstrate how these coupled applications have proven very effective at both well stimulation/skin reduction and scale-inhibitor placement before and after seawater breakthrough. The term “squimulation” is used by the local operations team to describe this simultaneous squeeze-and-stimulation process.Many similar fields are currently being developed in the Campos basin (Gulf of Mexico) and west Africa, and this paper presents a good example of best-practice sharing from another oil basin.
Digital Pathology Evaluation in the Multicenter Nephrotic Syndrome Study Network (NEPTUNE)
Authors: Barisoni Laura , Nast Cynthia C. , Jennette J. Charles , Hodgin Jeffrey B. , Herzenberg Andrew M. , Lemley Kevin V. , Conway Catherine M. , Kopp Jeffrey B. , Kretzler Matthias , Lienczewski Christa , Avila-Casado Carmen , Bagnasco Serena , Sethi Sanjeev , Tomaszewski John , Gasim Adil H. , Hewitt Stephen M. 
Published: February 2013

Summary
Pathology consensus review for clinical trials and disease classification has historically been performed by manual light microscopy with sequential section review by study pathologists, or multi-headed microscope review. Limitations of this approach include high intra- and inter-reader variability, costs, and delays for slide mailing and consensus reviews. To improve this, the Nephrotic Syndrome Study Network (NEPTUNE) is systematically applying digital pathology review in a multicenter study using renal biopsy whole slide imaging (WSI) for observation-based data collection. Study pathology materials are acquired, scanned, uploaded, and stored in a web-based information system that is accessed through a web-browser interface. Quality control includes metadata and image quality review. Initially, digital slides are annotated, with each glomerulus identified, given a unique number, and maintained in all levels until the glomerulus disappears or sections end. The software allows viewing and annotation of multiple slide sections concurrently. Analysis utilizes “descriptors” for patterns of injury, rather than diagnoses, in renal parenchymal compartments. This multidimensional representation via WSI, allows more accurate glomerular counting and identification of all lesions in each glomerulus, with data available in a searchable database. The use of WSI brings about efficiency critical to pathology review in a clinical trial setting, including independent review by multiple pathologists, improved intraobserver and interobserver reproducibility, efficiencies and risk reduction in slide circulation and mailing, centralized management of data integrity and slide images for current or future studies, and web-based consensus meetings. The overall effect is improved incorporation of pathology review in a budget neutral approach.
Decreased Serum Concentrations of 25-Hydroxycholecalciferol Are Associated With Increased Risk of Progression to Impaired Fasting Glucose and Diabetes
Authors: Tsur Anat , Feldman Becca S. , Feldhammer Ilan , Hoshen Moshe B. , Leibowitz Gil , Balicer Ran D. 
Published: February 2013

OBJECTIVE
To study the association between vitamin D status and the risk of incident impaired fasting glucose (IFG) and diabetes in a population-based cohort of diabetes-free subjects.

RESEARCH DESIGN AND METHODS
In a historical prospective cohort study of subjects from the Clalit Health Services database, which includes information on nearly 4 million people, diabetes-free subjects aged 40–70 years with serum 25-hydroxycholecalciferol (25-OHD) measurements available were followed for 2 years to assess the development of IFG and diabetes in five 25-OHD subgroups: ≥25, 25.1–37.5, 37.6–50, 50.1–75, and &gt;75 nmol/L.

RESULTS
The baseline cohort included 117,960 adults: 83,526 normoglycemic subjects and 34,434 subjects with IFG. During follow-up, 8,629 subjects (10.3% of the normoglycemic group) developed IFG, and 2,162 subjects (1.8% of the total cohort) progressed to diabetes. A multivariable model adjusted for age, sex, population group, immigrant status, BMI, season of vitamin D measurement, LDL and HDL cholesterol, triglycerides, estimated glomerular filtration rate, history of hypertension or cardiovascular disease, Charlson comorbidity index, smoking, and socioeconomic status revealed an inverse association between 25-OHD and the risk of progression to IFG and diabetes. The odds of transitioning from normoglycemia to IFG, from normoglycemia to diabetes, and from IFG to diabetes in subjects with a 25-OHD level ≤25 nmol/L were greater than those of subjects with a 25-OHD level &gt;75 nmol/L [odds ratio 1.13 (95% CI 1.03–1.24), 1.77 (1.11–2.83), and 1.43 (1.16–1.76), respectively].

CONCLUSIONS
Vitamin D deficiency appears to be an independent risk factor for the development of IFG and diabetes.
Screening for Diabetes and Prediabetes Should Be Cost-Saving in Patients at High Risk
Authors: Chatterjee Ranee , Narayan K.M. Venkat , Lipscomb Joseph , Jackson Sandra L. , Long Qi , Zhu Ming , Phillips Lawrence S. 
Published: February 2013

OBJECTIVE
Although screening for diabetes and prediabetes is recommended, it is not clear how best or whom to screen. We therefore compared the economics of screening according to baseline risk.

RESEARCH DESIGN AND METHODS
Five screening tests were performed in 1,573 adults without known diabetes—random plasma/capillary glucose, plasma/capillary glucose 1 h after 50-g oral glucose (any time, without previous fast, plasma glucose 1 h after a 50-g oral glucose challenge [GCTpl]/capillary glucose 1 h after a 50-g oral glucose challenge [GCTcap]), and A1C—and a definitive 75-g oral glucose tolerance test. Costs of screening included the following: costs of testing (screen plus oral glucose tolerance test, if screen is positive); costs for false-negative results; and costs of treatment of true-positive results with metformin, all over the course of 3 years. We compared costs for no screening, screening everyone for diabetes or high-risk prediabetes, and screening those with risk factors based on age, BMI, blood pressure, waist circumference, lipids, or family history of diabetes.

RESULTS
Compared with no screening, cost-savings would be obtained largely from screening those at higher risk, including those with BMI &gt;35 kg/m2, systolic blood pressure ≥130 mmHg, or age &gt;55 years, with differences of up to −46% of health system costs for screening for diabetes and −21% for screening for dysglycemia110, respectively (all P &lt; 0.01). GCTpl would be the least expensive screening test for most high-risk groups for this population over the course of 3 years.

CONCLUSIONS
From a health economics perspective, screening for diabetes and high-risk prediabetes should target patients at higher risk, particularly those with BMI &gt;35 kg/m2, systolic blood pressure ≥130 mmHg, or age &gt;55 years, for whom screening can be most cost-saving. GCTpl is generally the least expensive test in high-risk groups and should be considered for routine use as an opportunistic screen in these groups.