bluuebunny/crossref_metadata_2025_split huggingface dataset:
Open label study of escalating doses of oral treprostinil diethanolamine in patients with systemic sclerosis and digital ischemia: pharmacokinetics and correlation with digital perfusion
Authors: Shah Ami A , Schiopu Elena , Hummers Laura K , Wade Michael , Phillips Kristine , Anderson Cynthia , Wise Robert , Boin Francesco , Seibold James R , Wigley Fredrick , Rollins Kristan D 
Published: April 2013

Abstract
Introduction
Treprostinil diethanolamine is an innovative salt form of the prostacyclin analogue, treprostinil sodium, developed as an oral sustained release (SR) osmotic tablet. The availability of a formulation permitting convenient systemic delivery might have applicability to scleroderma vascular complications. We evaluated pharmacokinetics and perfusion in scleroderma patients with digital ischemia following escalating twice-daily doses of treprostinil diethanolamine SR.

Methods
Scleroderma patients with digital ulcers were enrolled in this dual-center, open-label, phase I pharmacokinetic study. Drug concentrations and perfusion, quantified by laser Doppler imaging, were measured over 12 hours at the 2 mg and 4 mg (or maximally tolerated) doses. Pharmacokinetic parameters were determined from individual plasma concentration versus time profiles using non-compartmental analysis methods. Digital perfusion and skin temperature were modeled as a function of log-transformed drug concentration and other covariates by performing repeated measures analyses using random effects models.

Results
Nineteen scleroderma patients (84% female, 53% limited scleroderma) received treprostinil diethanolamine SR with dose titration up to 4 mg twice daily as tolerated. Peak concentrations (mean maximum plasma concentration (Cmax) = 1,176 and 2,107 pg/mL) occurred approximately 3.6 hours after dose administration, and overall exposure (under the plasma concentration-time curve from time 0 to 12 hours post dose (AUC0-12) = 7,187 and 12,992 hr*pg/mL) was linear between the 2 mg and 4 mg doses. Perfusion and digital skin temperature were positively associated with log-transformed plasma concentration at the 4 mg dose (P = 0.015 and P = 0.013, respectively). The most frequent adverse events were similar to those seen with prostacyclin analogues.

Conclusions
Oral treprostinil diethanolamine was effectively absorbed in patients with scleroderma. Drug administration was temporally associated with improved cutaneous perfusion and temperature. Treprostinil diethanolamine may provide a new therapeutic option for Raynaud's phenomenon and the peripheral vascular disease of scleroderma.

Trial Registration
ClinicalTrials.gov NCT00848939.
Reduced Neuroanatomic Volumes in Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia
Authors: Zeller Bernward , Tamnes Christian K. , Kanellopoulos Adriani , Amlien Inge K. , Andersson Stein , Due-Tønnessen Paulina , Fjell Anders M. , Walhovd Kristine B. , Westlye Lars T. , Ruud Ellen 
Published: April 2013

Purpose To compare regional brain volumes in adult long-term survivors of childhood acute lymphoblastic leukemia (ALL) and healthy controls. Patients and Methods We investigated 130 survivors of childhood ALL diagnosed between 1970 and 2002 with magnetic resonance imaging (MRI) and neuropsychological testing at a median of 22.5 years after diagnosis. Morphometric analyses including whole-brain segmentation were performed using a validated automated procedure; 130 healthy adults served as controls. Results Compared with healthy controls, ALL survivors showed significantly smaller volumes of cortical gray matter, cerebral white matter, amygdala, caudate, hippocampus, thalamus, and estimated intracranial volume. Effect sizes ranged from small to medium. The strongest effect was found for the caudate, which on average was 5.2% smaller in ALL survivors. Caudate volumes were also smaller when controlling for intracranial volume, suggesting a specific effect. Neither age at diagnosis nor treatment variables such as radiation therapy or drug dose had a major impact on neuroanatomic volumes. Neuropsychological assessment revealed reduced processing speed, executive function, and verbal learning/memory in survivors compared with controls but no difference in estimated general intellectual ability. In ALL survivors, but not in controls, neuropsychological test results correlated with volumes of cortical gray matter, caudate, and thalamus as well as intracranial volume. Conclusion Structural MRI of long-term survivors of childhood ALL demonstrated smaller volumes of multiple brain structures compared with healthy controls. Because of possible selection biases, these results must be interpreted with caution. Future studies are required to clarify the significance of these findings and the neurobiologic mechanisms involved.
Analysis of plasma 3-methoxytyramine, normetanephrine and metanephrine by ultraperformance liquid chromatographytandem mass spectrometry: utility for diagnosis of dopamine-producing metastatic phaeochromocytoma
Authors: Peitzsch Mirko , Prejbisz Aleksander , Kroiß Matthias , Beuschlein Felix , Arlt Wiebke , Januszewicz Andrzej , Siegert Gabriele , Eisenhofer Graeme 
Published: April 2013

Background Measurements of plasma normetanephrine (NMN) and metanephrine (MN) provide a sensitive test for diagnosis of phaeochromocytomas and paragangliomas (PPGLs), but do not allow detection of dopamine-producing tumours. Here we introduce a novel mass spectrometric based method coupled to ultraperformance liquid chromatography (LC-MS/MS) for measuring NMN, MN and 3-methoxytyramine (MTY), the O-methylated metabolite of dopamine. Methods Specific collision-induced fragment ions assessed by multireaction monitoring transitions were used for identification, with quantification according to signal intensities of analytes relative to stable isotope labelled internal standards. Results for solid-phase extracted samples from 196 subjects analysed by LC-MS/MS were compared with those analysed by liquid chromatography with electrochemical detection (LC-ECD). Concentration ranges in 125 volunteers were compared with those from 63 patients with PPGLs, including 14 with metastatic disease. Results The LC-MS/MS method showed linearity over four orders of magnitude with analytical sensitivity sufficient to measure to 0.02 nmol/L. Intra- and inter-assay coefficients of variation ranged from 2.8% to 13.5%. NMN and MN were respectively measured 17% and 10% higher and MTY 26% lower by LC-MS/MS than by LC-ECD. Medians and ranges for 3-methoxytramine, NMN and MN were respectively 0.08 (0.03-0.13), 0.35 (0.13-0.95) and 0.15 (0.07-0.33) nmol/L in volunteers. Among patients with PPGLs, plasma methoxytyramine was six-fold higher in patients with than without metastastases (1.09 versus 0.19 nmol/L) and in three patients was the only metabolite increased. Conclusions The LC-MS/MS method enables accurate, selective and sensitive measurements of catecholamine O-methylated metabolites that should be particularly useful for screening and management of dopamine-producing metastatic PPGLs.
Demography and biochemistry of 2800 patients from a renal stones clinic
Authors: Walker Valerie , Stansbridge Elizabeth M , Griffin Damian G 
Published: April 2013

Background Because the causes of stones are uncertain, interventions to prevent recurrence have an insecure foundation. Progress depends on careful evaluation of stone formers. Methods A descriptive retrospective database study of 1983 men and 816 women from the Southampton stones clinic from 1990 to March 2007. Anonymized data from the first attendance were analysed using non-parametric statistical tests. Results Sex ratio (2.43:1), age (median 49 y, 2.5th-97.5th percentiles, 23-77 y men, 20-79 y women), recurrent stone formers (30%) and type of stone were similar to other centres. Women more often had a positive family history (24% versus 19% men), previous urinary infection (31% versus 5%) and structural urinary tract abnormality (14% versus 7%); more men had gout (5% versus 1%) and bladder outlet obstruction (3% versus <1%). Calcium, oxalate and uric acid excretion were increased in 43%, 17% and 22% respectively of men and 31%, 7% and 10% of women. Urinary calcium, oxalate and uric acid correlated significantly, r ranging from 0.149 to 0.311 for 24 h excretion and 0.510 to 0.695 for concentrations per litre. Twenty-two percent of men and 8% of women with normal parathyroid hormone had phosphaturia (excretion of phosphate corrected for glomerular filtration rate (TmPO4/GFR) < 0.70 mmol/L); 6% men and 1.6% women also had low plasma phosphate. Many variables correlated significantly but often weakly with age. Creatinine clearance, pH and (men) TmPO4/GFR decreased from 50 y, urine creatinine, calcium and citrate from 60 y. Conclusions Risk factors for stones differ between men and women, change with ageing and in some may have a genetic basis. The role of phosphaturia merits further exploration.
A Fast Estimate for the Population Recombination Rate Based on Regression
Authors: Lin Kao , Futschik Andreas , Li Haipeng 
Published: April 2013

Abstract
Recombination is a fundamental evolutionary force. Therefore the population recombination rate ρ plays an important role in the analysis of population genetic data; however, it is notoriously difficult to estimate. This difficulty applies both to the accuracy of commonly used estimates and to the computational efforts required to obtain them. Some particularly popular methods are based on approximations to the likelihood. They require considerably less computational efforts than the full-likelihood method with not much less accuracy. Nevertheless, the computation of these approximate estimates can still be very time consuming, in particular when the sample size is large. Although auxiliary quantities for composite likelihood estimates can be computed in advance and stored in tables, these tables need to be recomputed if either the sample size or the mutation rate θ changes. Here we introduce a new method based on regression combined with boosting as a model selection technique. For large samples, it requires much less computational effort than other approximate methods, while providing similar levels of accuracy. Notably, for a sample of hundreds or thousands of individuals, the estimate of ρ using regression can be obtained on a single personal computer within a couple of minutes while other methods may need a couple of days or months (or even years). When the sample size is smaller (n ≤ 50), our new method remains computational efficient but produces biased estimates. We expect the new estimates to be helpful when analyzing large samples and/or many loci with possibly different mutation rates.
High Density Metal Oxide (ZnO) Nanopatterned Platforms for Electronic Applications
Authors: Suresh Vignesh , Huang Meiyu Stella , Srinivasan Madapusi.P. , Krishnamoorthy Sivashankar 
Published: April 2013

ABSTRACTFabrication methodologies with high precision and tenability for nanostructures of metal and metal oxides are widely explored for engineering devices such as solar cells, sensors, non-volatile memories (NVM) etc. In this direction, metal and metal oxide nanopatterned arrays are the state-of-the-art platforms upon which the device structures are built where the tunable orderly arrangement of the nanostructures enhances the device performance. We describe here a coalition of fabrication protocols that employ block copolymer self-assembly and nanoimprint lithography (NIL) to obtain metal oxide nanopatterns with sub-100 nm spatial resolution. The protocols are easily scalable down to sub-50 nm and below.Nanopatterned arrays of ZnO created by using NIL assisted templates through area selective atomic layer deposition (ALD) and radio frequency (RF) sputtering find application in NVM and photovoltaics. We have employed NIL that produced nanoporous polymer templates using Si molds derived from block copolymer lithography (BCL) for pattern transfer into ZnO. The resulting ZnO nanoarrays were highly dense (8.6 x 109 nanofeatures per cm2) exhibiting periodic feature to feature spacing and width that replicated the geometric attributes of the template. Such nanopatterns find application in NVM, where a change in the density and periodicity of the arrays influences the charge storage characteristics. The above assembly and patterning protocols were employed to fabricate metal-oxide-semiconductor (MOS) capacitor devices for investigating application in NVM. Patterned ZnO nanoarrays were used as charge storage centres for the MOS capacitor devices. Preliminary results upon investigating the flash memory performance showed good flat-band voltage hysteresis window at a relatively low operating voltage due to high charge trap density.
Coherent effects in quantum dot-metallic nanoparticle systems: plasmonic induction of Rabi oscillation and ultra-high field enhancement
Authors: Sadeghi S. M. 
Published: April 2013

ABSTRACTWe theoretically show when single hybrid systems consisting of a metallic nanoparticle and a semiconductor quantum dot interact with a coherent light source (a laser field), quantum coherence in the quantum dot can dramatically influence the plasmonic field of the metallic nanoparticle. As a result, the quantum dot can self-renormalize the plasmonic field that it experiences. Using this we show when the applied laser field has a step-like amplitude rise, the effective field experienced by the quantum dot can exhibit strong oscillations with significantly high amplitudes for a short period of time. Our results also reveal the correlation between this effect and the Rabi flopping induced by plasmonic effects when a quantum dot is in the vicinity of a metallic nanoparticle. These results suggest that in a quantum dot-metallic nanoparticle system quantum coherence not only can change the magnitude of the field that the quantum dot experiences, but also, compared to the applied field, it can significantly increase the rate of its time variations. The results suggest that quantum dot-metallic nanoparticle systems can be appealing host for investigation of quantum plasmonic effects and photonic-plasmonic devices.
Atom-probe tomography of surface oxides and oxidized grain boundaries in alloys from nuclear reactors
Authors: Kruska Karen , Saxey David W , Terachi Takumi , Yamada Takuyo , Chou Peter , Calonne Olivier , Fournier Lionel , Smith George D W , Lozano-Perez Sergio 
Published: April 2013

ABSTRACTThe preparation of site-specific atom-probe tomography (APT) samples containing localized features has become possible with the use of focused ion beams (FIBs). This technique was used to achieve the analysis of surface oxides and oxidized grain boundaries in this paper. Transmission electron microscopy (TEM), providing microstructural and chemical characterization of the same features, has also been used, revealing crucial additional information.The study of grain boundary oxidation in stainless steels and nickel-based alloys is required in order to understand the mechanisms controlling stress corrosion cracking in nuclear reactors. Samples oxidized under simulated pressurized water reactor primary water conditions were used, and FIB lift-out TEM and APT specimens containing the same oxidized grain boundary were prepared and fully characterized. The results from both techniques were found fully consistent and complementary.Chromium-rich spinel oxides grew at the surface and into the bulk material, along grain boundaries. Nickel was rejected from the oxides and accumulated ahead of the oxidation front. Lithium, which was present in small quantities in the aqueous environment during oxidation, was incorporated in the oxide. All phases were accurately quantified and the effect of different experimental parameters were analysed.
Characteristics of Emergency Department Visits by Older Versus Younger Homeless Adults in the United States
Authors: Brown Rebecca T. , Steinman Michael A. 
Published: April 2013

Objectives. We compared the characteristics of emergency department (ED) visits of older versus younger homeless adults. Methods. We analyzed 2005–2009 data from the National Hospital Ambulatory Medical Care Survey, a nationally representative survey of visits to hospitals and EDs, and used sampling weights, strata, and clustering variables to obtain nationally representative estimates. Results. The ED visits of homeless adults aged 50 years and older accounted for 36% of annual visits by homeless patients. Although demographic characteristics of ED visits were similar in older and younger homeless adults, clinical and health services characteristics differed. Older homeless adults had fewer discharge diagnoses related to psychiatric conditions (10% vs 20%; P = .002) and drug abuse (7% vs 15%; P = .003) but more diagnoses related to alcohol abuse (31% vs 23%; P = .03) and were more likely to arrive by ambulance (48% vs 36%; P = .02) and to be admitted to the hospital (20% vs 11%; P = .003). Conclusions. Older homeless adults’ patterns of ED care differ from those of younger homeless adults. Health care systems need to account for these differences to meet the needs of the aging homeless population.
End-of-Life Care Issues: A Personal, Economic, Public Policy, and Public Health Crisis
Authors: Morhaim Dan K. , Pollack Keshia M. 
Published: April 2013

Advance directive documents are free, legal, and readily available, yet too few Americans have completed one. Initiating discussions about death is challenging, but progress in medical technology, which leads to increasingly complex medical care choices, makes this imperative. Advance directives help manage decision-making during medical crises and end-of-life care. They allow personalized care according to individual values and a likely reduction in end-of-life health care costs. We argue that advance directives should be part of the public health policy agenda and health reform.
Offshore Well Construction With Closed-Loop Cementing Technology
Authors: Dennis Moore , Hannegan Don 
Published: April 2013

Abstract
Achieving successful isolation of potential flow zones during well construction from floating rigs has historically been a formidable task, particularly on HPHT prospects. Operational challenges include actual vs. predicted leak-off test (LOT) values, margins of error in mud weights, high temperature compressibility at shoe depth and risk of inducing a fracture during pre-flush and/or cement slurry displacement. Wellbore strengthening operations may contribute to the relative unknown. Additionally, it is often assumed that the weakest component of the cementing operation is the last casing shoe, which may not be the case.
This presentation speaks to conducting dynamic formation integrity tests when drilling the open hole to be cased and cemented and applying managed pressure drilling (MPD) techniques as a means of increasing chances of getting a good cement job on the first attempt and in keeping with the intent of API Recommended Practice 65, Part 2- Isolating potential flow zones during well construction:
Preparatory - quantify the stability of the wellbore, actual wellbore pressures data for correlation with cementing simulator models & more efficient hole cleaning ahead of the cement.
Displacement - optimize fluid dynamics, ascertain in real-time an induced fracture and/or help ensure the column of plug in the tubing string is balanced with the annulus.
Curing -maintain more consistent annulus pressure on rigs experiencing wave heave & backpressure applications for minimizing the risk of channeling.
Testing – using MPD kit in lieu of cementing equipment or exercising the BOP.
Managed Pressure Drilling with Solids-Free Drilling Fluid Provides Cost-Efficient Drilling Solution for Subsea Carbonate Gas Development Wells
Authors: Setiawan Trigundai Budi , Bin Omar Mohammad Mizuar , Bin Sulaiman Mohd Zarkashi , Bin Musa Mohammad Zarir , Fadzli Muffaz , Nesan Thanavathy Patma , Wuest Chad H. , Toralde Julmar Shaun , Sridharan Prem Ananthan 
Published: April 2013

Abstract
The development of the Kanowit Field in offshore Sarawak, Malaysia requires the drilling of two subsea development wells using a semi-sub rig. Previous experience identified the need for solids-free drilling fluid to ensure maximum reservoir productivity and so that the quality of the produced gas is within required specifications. High reservoir pressure requires the use of high-density solids-free drilling fluids, but associated costs and the high probability of losing large volumes to the fractured carbonate reservoir made this option unsuitable.
A more cost-effective option was to use a less-dense solids-free drilling fluid and utilize managed pressure drilling (MPD) to be able to compensate for the difference in density with backpressure. MPD mitigated the loss circulation risk by controlling the level of overbalance to the minimum and MPD early kick and loss detection capabilities, used in conjunction with a statically underbalanced drilling fluid, also allowed for the collection of actual geopressure environment data that aided in the decision making process. Both wells were completed and tested with a maximum potential flow rate that exceeded the technical potential in initial projections.
The successful deployment of MPD with solids-free drilling fluids proves its technical and economic feasibility in carrying out subsea development drilling through carbonate reservoirs prone to severe circulation losses.
Supplementing Downhole Information to Enhance MPD and UBD Operations
Authors: Veeningen Daan , Adsit Rhys 
Published: April 2013

Abstract
Managed pressure and underbalanced drilling operations are predominantly conducted through the use of surface measurements and are heavily assisted by modeling subsurface conditions as downhole measurements have limited availability. Downhole information is typically absent during periods without flow and when using compressible fluids such as aerated mud.
Operational efficiency and wellsite safety would benefit by supplementing the models and surface data with direct measurements of subsurface conditions. Automation would be enabled and well control would meaningfully improve from self-sufficient downhole information by realizing the lowest pressures, while eliminating complex calculations and minimizing time spent on the choke.
Along-string annular pressure measurement and evaluation provides new downhole capabilities. Initial field deployments have demonstrated their utility and viability, but downhole ECD calculations through normalization of the absolute pressure measurements to hydrostatic depth do not properly account the distributed pressure sensing.
This paper proposes a new method for computing the along-string ECD values*, shows visualization for intuitive interpretation of the values and proposes a method for relative volume determination*. The new methodology with multiple sensors with non-hydrostatic pressure additions scaled by sensor depths show the need for two scale factors. Finally, an influx volume can be estimated across a wellbore section that is bounded by discrete drillstring pressure sensors. Examples are offered for pumping sweeps and a kick that is up the annulus and recommendations are offered for technologies that acquire pressure along the drillstring.
Managed Pressure Drilling (MPD), Under Balanced Drilling (UBD) and other operations that manage a tight pressure window benefit from the procedures and practices offered. Recommendations relevant to integration of downhole data with surface control systems for closed-loop and automated wellsite operations are offered.