bluuebunny/crossref_metadata_2025 huggingface dataset:
The Relation of the Kinetics of Pirmenol to Its Antiarrhythmic Efficacy
Authors: Johnson Brian F. , Haffajee Charles I. , Woodman Tracy , Sloan Kathy L.
Published: March 2013

In a single‐blind study the multiple oral dose kinetics of pirmenol were related to its efficacy in eight patients with frequent (mean, 631; range, 167–1374 beats/hour) premature ventricular contractions (PVC). Oral pirmenol was started at 100 mg bid for 48 hours and increased to 150 mg bid in six patients to obtain more than 70% suppression of PVC counts. Efficacy was achieved without side effects. Pirmenol decreased heart rate but not PR interval, QRS duration, or QTc interval. Peak plasma levels after the first 100‐mg dose occurred at 1 to 3 hours and ranged from 0.6 to 1.9 μg/mL. Plasma elimination half‐life ranged from 9.7 to 31 hours (mean, 18.3). From 67.4 to 171.3 mg pirmenol (mean, 102.3 mg) were recovered in the urine in 48 hours after the last dose. Cumulative excretion in divided urine collections was consistent with a mean elimination half‐life of 15 to 20 hours. The pharmacokinetics of pirmenol support oral twice‐daily administration. The minimum PVC suppressing plasma level is between 0.5 and 1.5 μg/mL.
Low‐Dose Acebutolol Given Once Daily in the Treatment of Chronic Angina Pectoris
Authors: Piña Ileana L. , Smith Elizabeth V. , Weidler Donald J.
Published: March 2013

Acebutolol, a beta‐1 selective beta blocker with intrinsic sympathomimetic activity has been shown to be an effective agent in chronic angina pectoris therapy, with twice or three times daily dosing. The long‐term effects of 400 mg of acebutolol given only once a day versus placebo on exercise hemodynamics, ST segment depression, and rate pressure product were studied. Eleven patients (mean age, 60 ± 12 years) with hypertension and chronic angina pectoris were enrolled. Resting heart rate was not significantly altered after therapy, (80 vs 72 bpm). Objective measurements from exercise treadmill tests showed significant reduction in peak heart rate from 130 to 103 bpm, systolic blood pressure from 197 to 167 mm Hg, rate pressure product (from 25 to 18 bpm‐mm Hg × 1000), and ST depression in patients receiving acebutolol compared with those receiving placebo. No significant adverse effects were reported. These data indicate that acebutolol may be efficacious as once daily therapy for chronic stable angina pectoris.
Alprazolam Pharmacokinetics in Women on Low‐Dose Oral Contraceptives
Authors: Scavone Joseph M. , Greenblatt David J. , Locniskar Ann , Shader Richard I.
Published: March 2013

Sixteen women chronically using low‐dose estrogen‐containing oral contraceptive steroids (OCs) and 23 drug‐free control women received a single 1‐mg oral dose of alprazolam. Multiple plasma samples drawn during 48 hours after the dose were analyzed by electron‐capture gas‐liquid chromatography. There were no significant differences between controls and oral contraceptive users in alprazolam volume of distribution (1.27 versus 1.39 L/kg), elimination half‐life (11.9 versus 12.3 hours), total clearance (1.36 versus 1.39 mL/min/kg), or total area under the plasma concentration versus time curve (227 versus 243 ng/mL × hr). Alprazolam free fraction in plasma was slightly but significantly greater in the oral contraceptive group as opposed to the control group (28.4 versus 27.0% unbound), respectively. However, comparison of free clearance between groups revealed no significant difference (4.61 versus 4.89 mL/min/kg, respectively). Thus, low‐dose estrogen‐containing oral contraceptives do not significantly influence the metabolic clearance of alprazolam.
Serum Binding of Indapamide in Health and Disease: Primary Role of α1‐acid glycoprotein
Authors: Urien Saik , Morin Didier , d'Athis Philippe , Coulomb Bertrand , Tillement Jean‐Paul
Published: March 2013

The serum concentrations of alpha‐1‐acid glycoprotein (AAG), albumin (HSA), and nonesterified fatty acids (NEFA), and the serum binding of indapamide were measured in four groups of individuals: control (healthy) subjects (N = 24), patients with inflammatory syndrome (N = 28), with hepatic (N = 20) and renal (N = 27) insufficiency. Indapamide serum binding was increased in patients with inflammatory syndrome (82.2 ± 3.4%, P < .001), decreased in patients with hepatic insufficiency (72.3 ± 5.9%, P < .001) and unchanged in patients with renal insufficiency (77.7 ± 2.8%) as compared with controls (78.2 ± 3.1%). A multivariate analysis indicated that these changes were mainly related to concomitant changes in AAG concentration (that explained 63% of intersubject variability in bound/free binding ratio), and to a lesser extent to HSA (that explained only 4% of the variability in the binding). These data show that the free fraction of the acidic drug indapamide in serum is affected by pathologic conditions in which changes in AAG concentration occur and that, unexpectedly, HSA plays a negligible role in the binding.
Pharmacodynamics, Clinical Indications, and Adverse Effects of Heparin
Authors: Freedman Michael D.
Published: March 2013

Heparins are a heterogenous group of naturally occurring glycosaminoglycans characterized by anticoagulant activity and a wide range of molecular weights (low molecular weight or fractionated heparins evolving within the past two decades). Cofactors for endogenous inhibitors of coagulation (antithrombin III and heparin cofactor II), heparin administration results in a hypocoagulable state. Various platelet activities, including inhibition of activity induced by platelet‐derived growth factors on vascular smooth muscle, also have been noted. Divorced of anticoagulant nature, novel applications may include a role in atherosclerosis prevention, acceleration of collateral coronary as well as peripheral circulation (i.e., angiogenesis), and continued (chronic) post‐myocardial infarction therapy. Established indications include treatment of various thrombotic diseases, unstable angina, and thrombosis chemoprophylaxis in medical/surgical patients. The antithrombotic potential of the heparins is used also in thrombosis management related to extracorporeal circulatory assistance or dialysis devices. Heparin's therapeutic potential in the postphlebitic syndrome as well as in acute treatment of myocardial infarction (primarily and adjunctively with various thrombolytic agents) continues to undergo evaluation; however, early data review shows favorable trends for its inclusion in situations that favor thrombus generation (e.g., anterior myocardial infarction).

Although associated with thrombocytopenia or hypertransaminasemia, the heparins are relatively well tolerated. In a small subset of patients, a severe thrombocytopenia may ensue, which generally resolves on medication withdrawal. As this class of glycosaminoglycans becomes better characterized, new indications may emerge for both native and the newer fractionated heparins.
Clinical Utility of Ambulatory Blood Pressure Monitoring in Target Organ Complications and Equipment Choices
Authors: Prisant L. Michael , Bottini P. Bruce , Carr Albert A.
Published: March 2013

Although population studies have demonstrated a relationship between casual office blood pressures and target organ events, the variability of these blood pressure measurements for individual patients has generated an interest in the role of ambulatory blood pressure monitoring for defining the presence of hypertension and assessing the response to therapy. Noninvasive devices provide fewer data than intra‐arterial ambulatory blood pressure monitoring devices, but are safer. No current noninvasive device performs well during ambulation. Rigorous evaluation of these rapid proliferating electronic devices is important, as would be the case with any new antihypertensive agent. Although ambulatory blood pressure measurements correlate better with target organ damage for groups of patients than do casual office measurements, the predictability and limited data on reproducibility for individual patients does not support widespread application for routine testing for hypertensive patients. Ambulatory blood pressure monitoring should be viewed as a standard research tool for the evaluation of new cardiovascular drugs.
Pharmacokinetics of Fluvastatin After Single and Multiple Doses in Normal Volunteers
Authors: Tse Francis L. S. , Jaffe James M. , Troendle August
Published: March 2013

The pharmacokinetics of fluvastatin, a potent inhibitor of hydroxymethylglutaryl‐CoA reductase and thus cholesterol synthesis, have been studied in 24 normal male volunteers who received [3H] fluvastatin in three different studies: a single‐dose study using oral doses of 2 or 10 mg, an absolute bioavailability study using doses of 2 mg intravenously or 10 mg orally, and a multiple‐dose study using 40 mg orally once daily for 6 days. Serial blood and plasma samples and complete urine and feces were collected and analyzed for total radioactivity as well as for intact fluvastatin. Fluvastatin was rapidly and almost completely (>90%) absorbed from the gastrointestinal tract, although the estimated bioavailability from the 2‐ and 10‐mg doses was only 19 to 29% because of extensive first‐pass metabolism. Fluvastatin pharmacokinetics appeared to be linear over the 2‐ to 10‐mg dose range, as indicated by dose‐proportional blood levels of total radioactivity and the parent drug. Absorbed fluvastatin was completely metabolized before excretion, the biliary/fecal route being the major excretory pathway. The recovery of radioactivity after a single dose was virtually complete within 120 hours. The terminal half‐lives of fluvastatin and total radioactivity averaged 0.5 to 1 hour and 55 to 71 hours, respectively, whereas the total body clearance of fluvastatin was 0.97 L/hour/kg. Repeated oral administration of 40‐mg doses of [3H]fluvastatin resulted in no time‐related change in pharmacokinetic characteristics, but this dose yielded greater than proportional increases in circulating levels of the parent drug, thus suggesting a saturable first‐pass effect on fluvastatin. During repeated daily administration, plasma levels of fluvastatin reached steady state after the first dose, whereas those of total radioactivity approached steady state after 6 days. The degree of accumulation of radioactivity, unlike that of the parent drug, was inconsistent with the terminal half‐life, but instead implied a shorter effective half‐life of 32 to 36 hours. It appears that the terminal phase of the blood radioactivity profile represents a minor metabolite that is reversibiy bound to and slowly released from a specific tissue depot, and that this binding involves a finite amount of drug regardless of the dose administered. The oral and intravenous administration of [3H]fluvastatin described in the present report was safe and well tolerated.
Sertraline Does Not Alter Steady‐State Concentrations or Renal Clearance of Lithium in Healthy Volunteers
Authors: Apseloff Glen , Wilner Keith D. , von Deutsch Daniel A. , Henry Eugenia B. , Tremaine Larry M. , Gerber Nicholas , Lazar Jeffrey D.
Published: March 2013

An open‐label, placebo‐controlled study was conducted to determine the effects of sertraline on the steady‐state levels and renal clearance of lithium in 20 healthy volunteers. Subjects received 600 mg of lithium twice daily for 9 days. On the evening of day 8, subjects received orally either placebo or 100 mg of sertraline; these were administered twice, 8 hours apart, beginning 2 hours after the evening dose of lithium. In a comparison of day 8 with day 9 (before administration of the morning doses of lithium), sertraline was associated with only a 0.01 mEq/L (1.4%) decrease in steady‐state levels and a 0.11 L/hour (6.9%) increase in the renal clearance of lithium. Neither change was statistically significant relative to placebo. Four subjects were excluded from analysis because of protocol violations or laboratory abnormalities unrelated to sertraline. Seven subjects who received lithium plus sertraline experienced side effects, mainly tremors, possibly related to treatment, whereas none of those administered lithium plus placebo experienced side effects. No sertraline‐related laboratory abnormalities were observed.
Intravenous and Oral Propafenone for Treatment of Tachycardia in Infants and Children: Pharmacokinetics and Clinical Response
Authors: Ito Shinya , Gow Robert , Verjee Zul , Giesbrecht Ester , Dodo Hidemi , Freedom Robert , Tonn George R. , Axelson James E. , Zalzstein Eli , Rosenberg Herschel C. , Koren Gideon
Published: March 2013

To elucidate contribution of an active metabolite to overall clinical responses to propafenone, steady‐state disposition of propafenone and its active metabolite and the clinical responses to treatment were examined in pediatric patients receiving intravenous or oral propafenone. There were more than ten‐fold interindividual differences in apparent clearance, resulting in a wide range of the steady‐state trough plasma concentrations of propafenone. The active metabolite, 5‐hydroxypropafenone, was detected in four of the six patients receiving oral propafenone; however, two neonates receiving oral propafenone and all eight receiving intravenous propafenone had no detectable levels of 5‐hydroxypropafenone in plasma. In nine patients for whom electrocardiographic (ECG) data were available, the PQ interval was significantly increased, whereas the QRS duration and the QTc interval were not. There was no close relationship between plasma concentrations of propafenone or 5‐hydroxypropafenone and ECG parameters. Lack of good correlation between serum concentrations and clinical response precludes using a serum‐concentration targeting strategy with propafenone therapy.
Application of Serum Nicotine and Plasma Cotinine Concentrations to Assessment of Nicotine Replacement in Light, Moderate, and Heavy Smokers Undergoing Transdermal Therapy
Authors: Lawson George M. , Hurt Richard D. , Dale Lowell C. , Offord Kenneth P. , Croghan Ivana T. , Schroeder Darrell R. , Jiang Nai‐S.
Published: March 2013

As part of a clinical trial investigating the level of nicotine replacement with different doses of transdermal therapy for smoking cessation, peak and trough serum nicotine and plasma cotinine concentrations were measured in 70 subjects while they were actively smoking (baseline) and daily for 6 consecutive inpatient days while they were receiving transdermal nicotine. Subjects were randomly assigned to a daily 24‐hour patch delivering a transdermal nicotine dose of 0, 11, 22, or 44 mg and stratified by self‐reported smoking rate as either light (10–15 cigarettes per day), moderate (16–30 cigarettes per day), or heavy (>30 cigarettes per day). Steady‐state concentrations of nicotine and cotinine were attained in 1 and 3 days, respectively, at all doses and were independent of baseline smoking rate. Mean percentage replacement of nicotine was calculated by dividing steady‐state peak nicotine or cotinine concentrations by their respective baseline concentrations. Significant underreplacement occurred in subjects receiving the 11 mg/day patch regardless of baseline smoking rate. Underreplacement also occurred in moderate and heavy smokers receiving 22 mg/day and in light smokers at this same dose. Complete replacement occurred only in subjects receiving the 44 mg/day patch. These results have several implications for transdermal nicotine therapy. First, with the higher nicotine and cotinine levels observed with heavier smoking, it is inherent that one size does not fit all, and there is a need to consider more individualization of dosage for nicotine patch therapy. Second, there is substantial underreplacement with the 22 mg/day dose in moderate to heavy smokers and in some light smokers. Third, even with twice the usual dose (i.e., 44 mg/day), there was no accumulation of either nicotine or cotinine. Plasma cotinine levels after achievement of steady state (i.e., after 3 days of patch therapy) can be collected at any time and used to calculate percent replacement using baseline levels.
Pharmacokinetics of Intravenous and Oral Losartan in Patients with Heart Failure
Authors: Lo Man‐Wai , Toh Jenny , Emmert Scott E. , Ritter Michael A. , Furtek Christine I. , Lu Hannah , Colucci Wilson S. , Uretsky Barry F. , MD Ewa Rucinska
Published: March 2013

The pharmacokinetics of a selective AT1‐subtype, nonpeptide, orally active, angiotensin II receptor antagonist, losartan, were characterized in 11 patients with heart failure (New York Heart Association class II, n = 6; class III, n = 4; class IV, n = 1) after oral and intravenous administration. In these patients, average plasma clearance of losartan was 566 mL/min, volume of distribution at steady‐state was 34 L, and terminal plasma half‐life was 1.5 hours. Average bioavailability was 36%. No clinically significant accumulation of losartan or its active metabolite, EXP3174, occurred after multiple‐dose oral administration for 7 to 8 days. Terminal plasma half‐life of EXP3174 after oral administration of losartan was 7.6 hours. The pharmacokinetics of losartan in patients in this study appear to be similar to those in healthy subjects studied previously.
A Novel Recombinant Soluble Human Thrombomodulin, ART‐123, Activates the Protein C Pathway in Healthy Male Volunteers
Authors: Nakashima Mitsuyoshi , Uematsu Toshihiko , Umemura Kazuo , Maruyama Ikuro , Tsuruta Kazuhisa
Published: March 2013

The effect of a novel recombinant soluble human thrombomodulin, ART‐123, on protein C activation was investigated by measuring plasma prothrombinase activity in four healthy male volunteers. ART‐123 at a dose of 0.3 mg was administered as a bolus intravenous injection for 1 minute. Plasma ART‐123 concentration and prothrombinase activity were determined before and immediately, 24, and 48 hours after injection, and thromboelastography was recorded before and immediately and 24 hours after injection. The mean elimination half‐life was 19.82 ± 2.10 hours. Compared with pretreatment levels, ART‐123 reduced prothrombinase activity by 44.2 ± 11.7%, 52.1 ± 10.8%, and 61.0 ± 14.7%, respectively, immediately, 24, and 48 hours after injection, suggesting that ART‐123 activated the protein C pathway. ART‐123 did not affect thromboelastography values. There were no abnormal findings for objective signs or laboratory tests, including blood pressure, heart rate, electrocardiogram, body temperature, hematology, coagulation and hemostatic parameters, blood chemistry, and urinalysis. Based on these observations, ART‐123 at a dose of 0.3 mg can activate the protein C pathway in healthy volunteers.
Pentoxifylline Potentiates In Vitro Lymphocyte Suppression by Glucocorticoids and Immunosuppressive Drugs
Authors: Briggs William A. , Eustace Joseph , Mathew Suresh , Gimenez Luis F. , Choi Michael , Scheel Paul J. , Burdick James
Published: March 2013

Pentoxifylline, which has immunomodulatory effects in addition to its better known rheologic effects, might potentiate the effectiveness of traditional immunosuppressive drugs. We therefore studied the suppressive effect of pentoxifylline in combination with clinically relevant concentrations of prednisolone, methylprednisolone, cyclosporine, tacrolimus, rapamycin, and mycophenolic acid on mitogen‐stimulated lymphocytes from 29 patients with glomerular diseases. Inhibition of lymphocyte proliferation obtained with 10−7 and 10−8 mol/L concentrations of the glucocorticoids and with 300 ng/mL cyclosporine was significantly increased when each was combined with 5, 25, or 50 μg/mL of pentoxifylline. The additive inhibitory effect of pentoxifylline in combination with 10−7 mol/L glucocorticoids was inversely proportional to the inhibitory effect of the 10−7 mol/L concentration of glucocorticoid alone, suggesting that the less sensitive the patient's cells, the greater the potentiation by pentoxifylline. The greatest degree of potentiation by pentoxifylline occurred when combined with the lower (10−8 mol/L) concentration of glucocorticoids. Pentoxifylline also significantly increased lymphocyte suppression in combination with 150 and 300 ng/mL concentrations of cyclosporine, 5 ng/mL of tacrolimus, 2.5 × 10−7 mol/L mycophenolic acid, and 10 ng/mL of rapamycin. These in vitro results suggest that pentoxifylline might have steroid‐sparing effects and contribute to improved clinical outcomes from immunosuppressive treatment of renal diseases.
SERS signal response and SERS/SERDS spectra of fluoranthene in water on naturally grown Ag nanoparticle ensembles
Authors: Ossig Robert , Kolomijeca Anna , Kwon Yong‐Hyok , Hubenthal Frank , Kronfeldt Heinz‐Detlef
Published: March 2013

We present experimental results of the time‐dependent Raman signal response of fluoranthene adsorbed on a naturally grown Ag nanoparticle ensemble, which serves as surface enhanced Raman scattering (SERS) substrate. In addition, SERS characteristics such as the concentration‐dependent calibration curves and the limit of detection (LOD) for fluoranthene in distilled water will be shown. The SERS substrate was prepared by Volmer–Weber growth under ultrahigh vacuum condition and exhibits a plasmon resonance wavelength at 491 nm. For the measurement of SERS signal response and SERS/shifted excitation Raman difference spectroscopy spectra of fluoranthene in water, experimental Raman setup containing a microsystem light source with two emission wavelengths (487.61 nm and 487.91 nm) was used. We experimentally demonstrate that the maximum SERS intensity is achieved 9 min after changing the analyte concentration from 0 nmol/l to 600 nmol/l. This response time is explained by a time‐dependent adsorption of the probe molecules onto the nanoparticles.

The LOD for fluoranthene in water was evaluated applying shifted excitation Raman difference spectroscopy (SERDS) at different molecule concentrations. For SERDS, two emission wavelengths of a prototype microsystem light source have been used for Raman excitation. The experimental results reveal that the LOD for the probe molecules is very low. Experimentally, we have detected a fluoranthene concentration of only 4 nmol/l, which is very close to our estimated LOD of 2 nmol/l. Thus, the presented Raman setup, with a SERS substrate, whose plasmon resonance coincides with the excitation wavelength for SERS measurements, is well suited for in‐situ trace detection of pollutant chemicals in water. Copyright © 2013 John Wiley & Sons, Ltd.
SERS detection of benzophenones on viologen functionalized Ag nanoparticles: application to breakfast cereals
Authors: Droghetti Enrica , Nicoletti Francesco P. , Guandalini Luca , Bartolucci Gianluca , Smulevich Giulietta
Published: March 2013

Silver (Ag) nanoparticles, as colloid suspensions or immobilized on an Ag plate, have been functionalized with the molecular assembler bis‐acridinium dication lucigenin (LG) and have been used as a chemical sensor system to detect benzophenone (BP) and 4‐methylbenzophenone (4MBP). The analytes strongly interact via their CO group with the N+–CH3 moiety of LG. Quantitative detection of BP and 4MBP had been obtained via a linear calibration curve by plotting the analyte concentration as a function of the intensity of the surface‐enhanced Raman scattering (SERS) signals. Therefore, the method has been applied to detect BP and 4MBP extracted from spiked cereal samples. In fact, these molecules are commonly used in the area of food packaging, and, due to their volatility, can migrate through the packaging into the food. The lowest amount of analytes revealed by the SERS method, in the analyte stock solutions and in the spiked breakfast cereal, was at trace level, 50 μM (9 ppm) and 70 μM (25 ppm), respectively. The calculated limit of detection value was 16 μM (3 ppm). The measurements were compared to the results of conventional gas chromatography‐tandem mass spectrometry (GC‐MS/MS) spectrometry of the BP concentrations in the spiked breakfast cereals. For a BP (or 4MBP) concentration above 70 μM (25 ppm), there was a very good agreement between the SERS sensor and the GC‐MS/MS determinations. In addition, no spurious bands due to other compounds present in the extract have been observed in the SERS spectra, indicating a good selectivity and specificity of the method. Thus, the SERS sensor can be applied, e.g. as a non‐quantitative alarm sensor for relatively high benzophenone concentrations in breakfast cereals. Copyright © 2013 John Wiley & Sons, Ltd.
Micro‐Raman investigations of early stage silver corrosion products occurring in sulfur containing atmospheres
Authors: Martina I. , Wiesinger R. , Schreiner M.
Published: March 2013

Silver is a soft, lustrous metal with the highest electrical and thermal conductivity. Due to these properties, it has many applications as a precious material both in pure and alloy form (ornaments, jewellery, utensils, coins), but also in several technological fields, considering silver compounds (e.g. photography, electric and electronic industry). As a consequence of this, silver and its by‐products are regularly exposed to different atmospheres where a wide spectrum of agents (e.g. moisture, temperature, air pollutants, UV light) may cause metal corrosion and alteration of their surface characteristics and properties. The aim of this research is to deepen the potential and applicability of micro‐Raman spectroscopy as a surface‐sensitive technique to investigate the initial steps of atmospheric corrosion throughout the identification of surface chemical reactions and corrosion products formed on silver substrates. In a previous study, micro‐Raman analysis was carried out on pure silver powder compounds, selected among the most expected corrosion products occurring on silver substrates, in order to optimize experimental conditions and to obtain reference spectra [1]. Subsequently highly pure silver samples were exposed for 24 h to different controlled laboratory atmospheres (synthetic air, relative humidity, SO2, H2S), particularly focusing on sulfur containing gases, and the resulting surface reactions. The experiments highlight micro‐Raman spectroscopy as a highly surface‐sensitive technique enabling to detect both adsorbed chemical species and crystalline corrosion products of only several monolayers of thickness. Furthermore, these investigations could show the trends of primary and secondary corrosion mechanisms and their mutual interaction occurring on silver substrates. Copyright © 2013 John Wiley & Sons, Ltd.
Validation of the Pittsburgh Sleep Quality Index Addendum for Posttraumatic Stress Disorder (PSQI‐A) in U.S. Male Military Veterans
Authors: Insana Salvatore P. , Hall Martica , Buysse Daniel J. , Germain Anne
Published: March 2013

Sleep disturbances are core symptoms of posttraumatic‐stress disorder (PTSD), yet they bear less stigma than other PTSD symptoms. Given the growing number of returning military veterans, brief, valid assessments that identify PTSD in a minimally stigmatizing way may be useful in research and clinical practice. The study purpose was to evaluate the psychometric properties of the Pittsburgh Sleep Quality Index Addendum for PTSD (PSQI‐A), and to examine its ability to identify PTSD cases among U.S. male military veterans. Male military veterans (N = 119) completed the PSQI‐A, as well as measures of sleep quality, combat exposure, posttraumatic stress, depression, and anxiety. Veterans with PTSD had higher PSQI‐A identified disruptive nocturnal behaviors than veterans without PTSD. The PSQI‐A had good internal consistency and convergent validity with sleep quality, combat exposure, PTSD symptoms, depression, and anxiety. A cutoff score ≥ 4 provided an area under the curve = .81, with 71% sensitivity, 82% specificity, and 60% positive and 83% negative predictive value for a clinical diagnosis of PTSD; correct classification was 74%. The PSQI‐A is a valid measure to possibly detect PTSD among male military veterans. Assessment of disruptive nocturnal behaviors may provide a cost‐effective, nonstigmatizing approach to PTSD screening without directly probing for trauma exposure(s).
Free‐Radical Polymerization with Long‐Chain Branching and Scission in a Continuous Stirred‐Tank Reactor
Authors: Tobita Hidetaka
Published: March 2013

Free‐radical polymerization that involves the polymer transfer reactions leading to both long‐chain branching and scission, as in the cases of high‐pressure olefin polymerization, is considered. In CSTR, the residence time distribution is broad and the primary polymer chain, whose residence time is large, is subjected to polymer transfer reaction for a longer time, leading to a larger number of branching and scission points. The distributions of both branching and scission density are much broader in a CSTR than in a batch, or equivalently, a PFR. The radius of gyration for larger sized polymers formed in a CSTR tends to be much smaller than that for randomly branched polymers.

magnified image
Early Pig Management in the Zagros Flanks: Reanalysis of the Fauna from Neolithic Jarmo, Northern Iraq
Authors: Price M. D. , Arbuckle B. S.
Published: March 2013

In this paper, we present a reanalysis of pig (Sus scrofa) remains from the Neolithic site of Qalat Jarmo, originally excavated in the 1940s and 1950s. Employing modern zooarchaeological techniques, not available during the initial analyses, we explore the nature of swine exploitation strategies and demonstrate that pigs were most likely managed by the early 7th millennium (Pottery Neolithic) and perhaps earlier. Comparing biometric data with those from other sites in the region, we show that the Jarmo pigs exhibit evidence for size decrease associated with intensive management, but had not yet achieved the degree of dental or post‐cranial size reduction seen in later Neolithic domestic populations. Although samples from the earliest (Pre‐Pottery) occupation of the site are small, there is some evidence to suggest that domestic pigs were present at Jarmo as early as the late 8th millennium cal. bc. In either case, Jarmo likely represents the earliest appearance of pig husbandry along the Zagros flanks, and we discuss the mechanisms by which Neolithic technologies, including domesticated animals, spread to new regions. This project emphasises the value of curated faunal assemblages in shedding new light on the spread of Neolithic economies. Copyright © 2013 John Wiley & Sons, Ltd.
Physician perceptions and beliefs of phase I trials in pediatric oncology
Authors: Gilliam Margaux B. , Madan‐Swain Avi , Adams Julia M. , Pressey Joseph G.
Published: March 2013

The identification and referral of candidate patients for phase I trials relies heavily on pediatric oncologists who must balance their own perceptions of phase I trials with the desires of the patient and his/her family. A survey was sent to 419 physicians practicing pediatric oncology at 30 different institutions. Results indicated significant differences between physicians who practiced at institutions that participated in phase I consortia versus those who did not. The findings of the survey may be used to enhance the design and execution of phase I trials and to educate oncologists about the goals of phase I trials. Pediatr Blood Cancer 2013;60:E67–E69. © 2013 Wiley Periodicals, Inc.
A Rapid Method for Total Β‐Escin Analysis in Dry, Hydroalcoholic and Hydroglycolic Extracts of Aesculus hippocastanum L. by Capillary Zone Electrophoresis
Authors: Dutra Lidiane S. , Leite Magda N. , Brandão Marcos A. F. , de Almeida Priscila Aparecida , Vaz Fernando A. S. , de Oliveira Marcone A. L.
Published: March 2013

Introduction

Seeds of Aesculus hippocastanum L. are used in European phytotherapy to treat inflammatory and vascular problems, and also to help in the regulation of the microcirculation. Thus, the quality control of herbal medicines using this species is important.

Objective

To develop and to optimise a capillary zone electrophoresis method to determine total β‐escin in different extracts of A. hippocastanum L.

Methods

The optimal condition found through chemometric approach was: 25 mmol/L of bicarbonate–carbonate buffer, pH 10.3; +20 kV of voltage; 20°C of cartridge temperature; direct ultraviolet detection at 226 nm; 13 mbar injection for 5 s and analysis time within 6 min.

Results

Repeatability, coefficient of variation (CV; %) = 3.19, 3.07 and 1.89 (n = 12), and intermediate precision, CV (%) = 3.05, 3.53 and 2.99 (n = 24) for dry, hydroalcoholic and hydroglycolic extracts, respectively were achieved. The accuracy was evaluated through recovery tests in concentration levels of 100, 150 and 200 g/L, ranging from 98.17 to 104.68%. The proposed method exhibited linearity (r = 0.9983) in the concentration range from 101.4 to 907.2 g/L and limits of detection and quantification equal to 11.63 and 38.76 g/L respectively.

Conclusion

A fast and reliable methodology for determination of total β‐escin was successfully validated and applied on extracts of A. hippocastanum L. demonstrating its usefulness to quality control of medicines containing this plant species. Copyright © 2013 John Wiley & Sons, Ltd.
Syntheses and properties of poly(diethyl vinylphosphonate) initiated by lanthanide tris(borohydride) complexes: Polymerization controllability and mechanism
Authors: Li Jing , Ni Xufeng , Ling Jun , Shen Zhiquan
Published: March 2013

Polymerization of diethyl vinylphosphonate (DEVP) is achieved by using lanthanide tris(borohydride) complexes, Ln(BH4)3(THF)3 (Ln = Y, La, Nd, Sm, Gd, Dy, Lu) as an initiator. The characteristics and mechanism of polymerization as well as the properties of the resulting poly(diethyl vinylphophonate)s (PDEVPs) are studied. The effects of the lanthanide elements, the molar ratios of monomer to initiator ([M]/[ln]), reaction temperature and time on polymerization have been investigated in detail. The optimized polymerization conditions are 40 °C, 1 h in bulk with [M]/[ln] = 300. The kinetic study indicates that the polymerization of DEVP undergoes a controlled manner as the molecular weights (MWs) of PDEVPs increase with monomer conversion linearly maintaining moderate MW distribution (1.7–1.9). Additionally, a coordination anionic polymerization mechanism is proved by end‐group analysis with ESI mass and 1H NMR spectroscopy. The obtained PDEVPs have low glass transition temperature (Tg = −62 °C) and high thermal decomposition temperature (Td > 300 °C) determined by differential scanning calorimetry and thermogravimetric analysis respectively. The thermosensitive behavior of PDEVP is characterized by evaluating the lower critical solution temperature of PDEVP in water by ultraviolet transmittance. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 2409–2415
Cationic cyclopolymerization of divinyl ethers with norbornane‐, norbornene‐, or adamantane‐containing substituents: Synthesis of cyclopoly(divinyl ether)s with bulky rigid side chains leading to high glass transition temperature
Authors: Morita Kazuhiro , Hashimoto Tamotsu , Urushisaki Michio , Sakaguchi Toshikazu
Published: March 2013

Cationic cyclopolymerizations of 2,2‐bis(vinyloxymethyl)bicyclo[2.2.1]heptane (1), 5,5‐bis(vinyloxymethyl)‐2‐bicyclo[2.2.1]heptene (2), and 2,2‐bis(vinyloxymethyl)tricyclo[3.3.1.1]3, 7decane (3), divinyl ethers with a norbornane, norbornene, or adamantane unit, respectively, were investigated with the HCl/ZnCl2 initiating system in toluene and methylene chloride at −30 °C. All the reactions proceeded quantitatively to give gel‐free, soluble polymers in organic solvents. The number‐average molecular weight (Mn) of the polymers increased in direct proportion to monomer conversion and further increased on addition of a fresh monomer feed to the almost completely polymerized reaction mixture. The contents of the unreacted vinyl groups in the produced soluble polymers were less than ∼10 mol %, and therefore, the degree of cyclization of the polymers was determined to be over ∼90%. These facts show that cyclopolymerization of 1, 2, and 3 exclusively occurred and the poly(vinyl ether)s with the cyclized repeating units and polycyclic pendants were obtained with their molecular weights being regulated. BF3OEt2 initiator also caused cyclopolymerization of 1, 2, and 3 to give the corresponding high‐molecular‐weight cyclopolymers quantitatively. Glass transition temperatures (Tg's) of poly(1) and poly(2) were 165–180 °C, and Tg's of poly(3) were 211–231 °C; these values are very high as vinyl ether polymers. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 2445–2454
Protein Adhesion on Atmospheric Plasma Deposited Quaternary Ammonium Salt Coatings
Authors: Donegan Mick , Dowling Denis P.
Published: March 2013

This study investigates protein adhesion on nm thick helium atmospheric plasma deposited quaternary ammonium salt (QAS) coatings. The adhesion of the proteins BSA, IgG and Fg was evaluated on coated and uncoated silicon wafer substrates. This study was carried out in PBS solution, under flow conditions using ellipsometry. The QAS was found to exhibit a low level of solubility in PBS over time (approx. 2 nm h−1). On addition of both the IgG and Fg proteins, it was found that a protective protein layer of 7 and 2 nm respectively was formed, which prevented further dissolution of the QAS. In contrast the 1 nm thick BSA protein layer, which formed on the QAS, was insufficiently thick to prevent the slow dissolution of the salt. It was concluded that the charge and structure of the protein influences its adhesion on the QAS surface.

magnified image
Elimination of E. Faecalis by a New Non‐Thermal Atmospheric Pressure Plasma Handheld Device for Endodontic Treatment. A Preliminary Investigation
Authors: Jablonowski Lukasz , Koban Ina , Berg Marie H. , Kindel Eckhard , Duske Kathrin , Schröder Karsten , Weltmann Klaus‐Dieter , Kocher Thomas
Published: March 2013

The aim of this study was to investigate the feasibility of an atmospheric pressure plasma jet (PJ) for endodontic treatment and to compare the antimicrobial efficiency with conventional irrigation solutions (chlorhexidine digluconate (CHX), sodium hypochlorite (NaOCl)) against intracanal bacteria (E. faecalis) using a standardized simulated root canal model. The disinfection efficiency was determined by number of colony forming units. Scanning electron microscopy was used to investigate the effect of the treatment procedures on bacteria inside the root canal. The PJ achieved a significantly higher microbial reduction than chemical CHX irrigation and a comparable one with NaOCl. The application of PJ for endodontic treatment could provide a new possibility of controlling endodontic infection.

magnified image
Perfluoro‐tert‐butyl‐homoserine as a sensitive 19F NMR reporter for peptide–membrane interactions in solution
Authors: Buer Benjamin C. , Levin Benjamin J. , Marsh E. Neil G.
Published: March 2013

Fluorine (19F) NMR is a valuable tool for studying dynamic biological processes. However, increasing the sensitivity of fluorinated reporter molecules is a key to reducing acquisition times and accessing transient biological interactions. Here, we evaluate the utility a novel amino acid, l‐O‐(perfluoro‐t‐butyl)‐homoserine (pFtBSer), that can easily be synthesized and incorporated into peptides and provides greatly enhanced sensitivity over currently used 19F biomolecular NMR probes. Incorporation of pFtBSer into the potent antimicrobial peptide MSI‐78 results in a sharp 19F NMR singlet that can be readily detected at concentrations of 5 µm and lower. We demonstrate that pFtBSer incorporation into MSI‐78 provides a sensitive tool to study binding through 19F NMR chemical shift and nuclear relaxation changes. These results establish future potential for pFtBSer to be incorporated into various proteins where NMR signal sensitivity is paramount, such as in‐cell investigations. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.
Polarization dependent photocurrent spectroscopy for identification of quantum confined interband transitions in type‐II InAs/GaSb superlattices
Authors: Gautam Nutan , Barve Ajit Vijay , Krishna Sanjay
Published: March 2013

We report on the use of polarization sensitive photocurrent spectroscopy for identifying the participating transitions in type‐II superlattices based on InAs/GaSb system. Prominent features in measured transverse magnetic and transverse electric photocurrent response on photodetectors have been analyzed to unambiguously predict the correct ordering of hole minibands as heavy and light hole minibands. Measurements carried out on both midwave infrared as well as long wave infrared superlattice detectors reveal the order of the participating valence minibands as: heavy‐hole1, light‐hole1and light‐hole2, with the increasing energy. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A practical MGA‐ARIMA model for forecasting real‐time dynamic rain‐induced attenuation
Authors: Gong Shuhong , Gao Yifeng , Shi Houbao , Zhao Ge
Published: March 2013

The novel and practical modified genetic algorithm (MGA)‐autoregressive integrated moving average (ARIMA) model for forecasting real‐time dynamic rain‐induced attenuation has been established by combining genetic algorithm ideas with the ARIMA model. It is proved that due to the introduction of MGA into the ARIMA(1,1,7) model, the MGA‐ARIMA model has the potential to be conveniently applied in every country or area by creating a parameter database used by the ARIMA(1,1,7) model. The parameter database is given in this paper based on attenuation data measured in Xi'an, China. The methods to create the parameter databases in other countries or areas are offered, too. Based on the experimental results, the MGA‐ARIMA model has been proved practical for forecasting dynamic rain‐induced attenuation in real time. The novel model given in this paper is significant for developing adaptive fade mitigation technologies at millimeter wave bands.
Design and semiparametric analysis of non‐inferiority trials with active and placebo control for censored time‐to‐event data
Authors: Kombrink Karola , Munk Axel , Friede Tim
Published: March 2013

The clinical trial design including a test treatment, an active control and a placebo is called the gold standard design. In this paper, we develop a statistical method for planning and evaluating non‐inferiority trials with gold standard design for right‐censored time‐to‐event data. We consider both lost to follow‐up and administrative censoring. We present a semiparametric approach that only assumes the proportionality of the hazard functions. In particular, we develop an algorithm for calculating the minimal total sample size and its optimal allocation to treatment groups such that a desired power can be attained for a specific parameter constellation under the alternative. For the purpose of sample size calculation, we assume the endpoints to be Weibull distributed. By means of simulations, we investigate the actual type I error rate, power and the accuracy of the calculated sample sizes. Finally, we compare our procedure with a previously proposed procedure assuming exponentially distributed event times. To illustrate our method, we consider a double‐blinded, randomized, active and placebo controlled trial in major depression. Copyright © 2013 John Wiley & Sons, Ltd.
A random forest approach for competing risks based on pseudo‐values
Authors: Mogensen Ulla B. , Gerds Thomas A.
Published: March 2013

Random forest is a supervised learning method that combines many classification or regression trees for prediction. Here we describe an extension of the random forest method for building event risk prediction models in survival analysis with competing risks. In case of right‐censored data, the event status at the prediction horizon is unknown for some subjects. We propose to replace the censored event status by a jackknife pseudo‐value, and then to apply an implementation of random forests for uncensored data. Because the pseudo‐responses take on values on a continuous scale, the node variance is chosen as split criterion for growing regression trees. In a simulation study, the pseudo split criterion is compared with the Gini split criterion when the latter is applied to the uncensored event status. To investigate the resulting pseudo random forest method for building risk prediction models, we analyze it in a simulation study of predictive performance where we compare it to Cox regression and random survival forest. The method is further illustrated in two real data sets. Copyright © 2013 John Wiley & Sons, Ltd.
On use of partial area under the ROC curve for evaluation of diagnostic performance
Authors: Ma Hua , Bandos Andriy I. , Rockette Howard E. , Gur David
Published: March 2013

Evaluation of diagnostic performance is a necessary component of new developments in many fields including medical diagnostics and decision making. The methodology for statistical analysis of diagnostic performance continues to develop, offering new analytical tools for conventional inferences and solutions for novel and increasingly more practically relevant questions.

In this paper, we focus on the partial area under the Receiver Operating Characteristic (ROC) curve or pAUC. This summary index is considered to be more practically relevant than the area under the entire ROC curve (AUC), but because of several perceived limitations, it is not used as often. To improve interpretation, results for pAUC analysis are frequently reported using a rescaled index such as the standardized partial AUC proposed by McClish (1989).

We derive two important properties of the relationship between the ‘standardized’ pAUC and the defined range of interest, which could facilitate a wider and more appropriate use of this important summary index. First, we mathematically prove that the ‘standardized’ pAUC increases with increasing range of interest for practically common ROC curves. Second, using comprehensive numerical investigations, we demonstrate that, contrary to common belief, the uncertainty about the estimated standardized pAUC can either decrease or increase with an increasing range of interest.

Our results indicate that the partial AUC could frequently offer advantages in terms of statistical uncertainty of the estimation. In addition, selection of a wider range of interest will likely lead to an increased estimate even for standardized pAUC. Copyright © 2013 John Wiley & Sons, Ltd.
Visual search
Authors: Chan Louis K.H. , Hayward William G.
Published: March 2013

Visual search is the act of looking for a predefined target among other objects. This task has been widely used as an experimental paradigm to study visual attention, and because of its influence has also become a subject of research itself. When used as a paradigm, visual search studies address questions including the nature, function, and limits of preattentive processing and focused attention. As a subject of research, visual search studies address the role of memory in search, the procedures involved in search, and factors that affect search performance. In this article, we review major theories of visual search, the ways in which preattentive information is used to guide attentional allocation, the role of memory, and the processes and decisions involved in its successful completion. We conclude by summarizing the current state of knowledge about visual search and highlight some unresolved issues.WIREs Cogn Sci2013, 4:415–429. doi: 10.1002/wcs.1235

This article is categorized under:

Psychology > Perception and Psychophysics