bluuebunny/crossref_metadata_2025_split huggingface dataset:
A rapid direct fluorescent assay for cell-free DNA quantification in biological fluids
Authors: Goldshtein Hagit , Hausmann Michael J , Douvdevani Amos 
Published: September 2009

Background Circulating cell-free DNA (CFD) levels may be elevated in trauma, stroke, sepsis, pre-eclampsia and cancer. Owing to the complex and expensive methodology, detection of CFD has hitherto been confined to research laboratories. This study presents a simple, inexpensive and accurate test for CFD. Methods Using the commercial fluorescent SYBR® Gold stain, biological fluids were directly assayed for CFD without prior DNA extraction and amplification. Stain was added to the sample in 96-well plates (final stain dilution: 1:10,000) and fluorescence was read by a fluorometer (excitation wavelength 488 nm, emission wavelength 535 nm). Results The assay was validated with serum, whole blood, urine and supernatant of cell cultures. Specificity and linearity were demonstrated over a wide range of concentrations; the results correlated with the conventional quantitative polymerase chain reaction assay of β-globin ( R2 = 0.9987, P < 0.001). The assay was not affected by exposure of whole blood or serum to room temperature for four or 24 h, respectively. Intra and day-to-day coefficients of variation (16–4.8% and 31–8%, respectively; depending on DNA level) compared well with published data describing more work-intensive tests. The limit of quantitation (170 ng/mL) was below the mean DNA level in a cohort of normal individuals (471 [203] ng/mL). Finally, free DNA in supernatant of cell cultures after cell lysis accurately reflected cell number ( R2 = 0.974, P < 0.0001). Conclusions The direct SYBR® Gold assay proved to be an accurate and simple technique for measuring CFD in biological fluids.
A convenient enzyme-linked immunosorbent assay for rapid screening of anti-adeno-associated virus neutralizing antibodies
Authors: Ito Tetsuo , Yamamoto Shigekazu , Hayashi Tsukasa , Kodera Mika , Mizukami Hiroaki , Ozawa Keiya , Muramatsu Shin-ichi 
Published: September 2009

Background Recombinant adeno-associated virus vectors based on serotype 2 (AAV-2) have become leading vehicles for gene therapy. Most humans in the general population have anti-AAV-2 antibodies as a result of naturally acquired infections. Pre-existing immunity to AAV-2 might affect the functional and safety consequences of AAV-2 vector-mediated gene transfer in clinical applications. Methods An enzyme-linked immunosorbent assay (ELISA) method was developed using microwell plates coated with intact particles of recombinant AAV-2 vectors, and horseradish peroxidase-conjugated anti-human immunoglobulin G (HRP-IgG). Neutralizing antibody titres were analysed by assessing the ability of serum antibody to inhibit transduction into HEK293 cells of AAV vectors that express β-galactosidase. Results Anti-AAV-2 antibodies were detected by ELISA in two of 20 healthy subjects. The positivity criterion (optical density >0.5) in ELISA corresponded to the cut-off value (320-fold dilution of serum) in the AAV-2 neutralization assay. Influences of interfering substances were not observed. Conclusion This ELISA method may be useful for rapid screening of anti-AAV-2 neutralizing antibodies in candidates for gene therapy.
Pay for perfomance and the quality of diabetes management in individuals with and without co-morbid medical conditions
Authors: Millett Christopher , Bottle Alex , Ng Anthea , Curcin Vasa , Molokhia Mariam , Saxena Sonia , Majeed Azeem 
Published: September 2009

Summary Objective To examine the impact of the Quality and Outcomes Framework, a major pay-for-performance incentive introduced in the UK during 2004, on diabetes management in patients with and without co-morbidity. Design Cohort study comparing actual achievement of treatment targets in 2004 and 2005 with that predicted by the underlying (pre-intervention) trend in diabetes patients with and without co-morbid conditions. Setting A total of 422 general practices participating in the General Practice Research Database. Main outcomes measures Achievement of diabetes treatment targets for blood pressure (< 140/80 mm Hg), HbA1c (≤ 7.0%) and cholesterol (≤ 5 mmol/L). Results The percentage of diabetes patients with co-morbidity reaching blood pressure and cholesterol targets exceeded that predicted by the underlying trend during the first two years of pay for perfomance (by 3.1% [95% CI 1.1–5.1] for BP and 4.1% [95% CI 2.2–6.0] for cholesterol among patients with ≥ 5 co-morbidities in 2005). Similar improvements were evident in patients without co-morbidity, except for cholesterol control in 2004 (−0.2% [95% CI −1.7–1.4]). The percentage of patients meeting the HbA1c target in the first two years of this program was significantly lower than predicted by the underlying trend in all patients, with the greatest shortfall in patients without co-morbidity (3.8% [95% CI 2.6–5.0] lower in 2005). Patients with co-morbidity remained significantly more likely to meet treatment targets for cholesterol and HbA1c than those without after the introduction of pay for perfomance. Conclusions Diabetes patients with co-morbid conditions appear to have benefited more from this pay-for-performance program than those without co-morbidity.
Cell-Free DNA as a Noninvasive Acute Rejection Marker in Renal Transplantation
Authors: García Moreira Vanessa , Prieto García Belen , Baltar Martín Jose M , Ortega Suárez Francisco , Alvarez Francisco V 
Published: September 2009

AbstractBackground: Acute rejection (AR) is a key conditioning factor for long-term graft function and survival in renal transplantation patients. The standard care with creatinine measurements and biopsy upon allograft dysfunction implies that AR is usually detected at advanced stages. Rapid noninvasive biomarkers of rejection are needed to improve the management of these patients. We assessed whether total cell-free DNA (tCF-DNA) and donor-derived cell-free DNA (ddCF-DNA) were useful markers for this purpose, both in plasma and in urine.Methods: Plasma and urine samples from 100 renal transplant recipients were obtained during the first 3 months after transplantation. tCF-DNA and ddCF-DNA were analyzed by quantitative PCR for the HBB (hemoglobin, beta) and the TSPY1 (testis specific protein, Y-linked 1) genes, respectively. We observed 19 episodes of AR, as well as other complications, such as acute tubular necrosis, nephrotoxicity, and infections.Results: Plasma tCF-DNA concentrations increased markedly during AR episodes, often before clinical diagnosis, and returned to reference values after antirejection treatment. A cutoff plasma tCF-DNA concentration of 12 000 genome equivalents/mL correctly classified AR and non-AR episodes in 86% of posttransplantation complications (diagnostic sensitivity, 89%; specificity, 85%). Although similar increases were observed during severe posttransplantation infections, use of the combination of plasma tCF-DNA and procalcitonin (PCT), a specific marker of sepsis, significantly improved the diagnostic specificity (to 98%; 95% CI, 92%–100%), with 97% of the episodes being correctly classified. Use of transrenal DNA and ddCF-DNA concentrations did not add relevant information.Conclusions: Given that renal biopsy is the gold standard for detecting AR, analysis of both plasma tCF-DNA and PCT could permit a more selective use of this invasive procedure.
Effect of Implants on Maximum Bite Force in Edentulous Patients
Authors: Rismanchian Mansour , Bajoghli Farshad , Mostajeran Zahra , Fazel Akbar , Eshkevari Psadr 
Published: September 2009

Abstract
One of the main goals of prosthetic dentistry is to reconstruct the masticatory system. Replacing missing teeth by complete or partial denture is associated with decreased bite force and patient satisfaction. The aim of the present study was to measure the maximum bite force (MBF) and to evaluate patients' satisfaction from their conventional complete dentures and their mandibular implant-supported overdentures opposed by complete denture. In this cross sectional analytical descriptive study, seventy-five 45- to 65-year-old patients were divided into 3 groups wearing: (1) conventional complete dentures for up to 6 months; (2) conventional complete dentures for 10 years or more; and (3) complete maxillary dentures opposing mandibular implant-supported overdentures. Bite force was measured by means of electronic bite force measuring device with strain gauges. Three measurements were made on each side on the first molar region and the mean values were recorded. Patient satisfaction was also recorded using questionnaires. Results were analyzed by analysis of variance (ANOVA), t test, chi-square, and Pearson correlation test. The mean MBF for the first, the second, and the third group was, respectively, 5.65 ± 1.46 kgf, 7.01 ± 2.1 kgf, and 12.22 ± 27 kgf. The difference between MBF in patients with overdentures and in patients with conventional complete dentures was statistically significant (P  =  .001). Patient satisfaction with mandibular implant-supported overdentures was recorded as “great.” Results indicated MBF in the patients with mandibular implant-supported overdentures was significantly higher than that of patients with conventional complete dentures. This difference may indicate the important role of dental implants in the improvement of bite force and chewing efficiency and therefore patients' satisfaction.
Religious Involvement and Cigarette Smoking among Iranian University Students
Authors: Nakhaee Nouzar , Divsalar Kouros , Jadidi Nadjme 
Published: September 2009

Objectives: To find out the prevalence of cigarette smoking in a group of Iranian Muslim students and also to find out if there is a relationship between religious practices and cigarette smoking. Methods: In this cross-sectional study, 950 university students in Kerman, Iran were asked to fill out a self-administered questionnaire consisting of questions on demographic data, cigarette smoking, and religious practices. It was explained that the study was anonymous and voluntary, and confidentiality was assured. Results: All 833 subjects who participated in the study were Muslims, 54.1% of whom were female and 89.3% were single. Approximately 40% of male students and 5.8% of the female ones were smokers. Based on bivariate analysis, some differences were noted in the prevalence of smoking according to gender, marital status, income, average university scores, close friend's smoking, parental smoking, reading the Quran, saying prayers, mosque attendance, and fasting. Using multivariate analysis, male gender, higher income, lower average exam scores, and close friend's smoking being associated with the likelihood to smoke cigarettes. The odds ratio for cigarette smoking in the upper tertile compared with those in the lower tertile of religious activity was 0.53 (CI 95% 0.33–0.84). Conclusion: Religious activities may have a protective role against cigarette smoking among Muslim college students in the country.
The Role of Cognitive Impairment and Caregiver Support in Diabetes Management of Older Outpatients
Authors: Feil Denise G. , Pearman Ann , Victor Tara , Harwood Dylan , Weinreb Jane , Kahle Kristin , Unützer Jürgen 
Published: September 2009

Objectives: To examine the role of cognitive impairment and caregiver support in diabetes care adherence and glycemic control. Methods: Fifty-one veteran male outpatients (27 with caregivers) aged 60 years and older with type 2 diabetes were evaluated for cognitive impairment with the Cognitive Abilities Screening Instrument. Patients or caregivers completed diabetes self-care and depression scales. Medical morbidity information and HbA1c plasma levels at baseline and 1 year later were obtained from electronic medical records. Results: Greater cognitive impairment ( F = 5.1, p < .05), and presence of a caregiver ( F = 5.3, p < .05), were independently associated with worse diabetes care adherence (adjusting for age, education, medical comorbidity, and depression). In addition, Mean HbA1c levels were worse in the cognitively impaired group with caregivers relative to the three other groups ( F = 4.10, p < .05, η2 =.09). One year later, mean HbA1c levels rose from 7.7 to 8.2% in the cognitively impaired group with caregivers. Conclusion: Cognitive impairment is associated with worse diabetes care management. Surprisingly, the presence of a caregiver is not protective. Further research is necessary to examine the healthcare needs of cognitively impaired, diabetic patients and their caregivers.
Are Metabolically Normal but Obese Individuals at Lower Risk for All-Cause Mortality?
Authors: Kuk Jennifer L. , Ardern Chris I. 
Published: September 2009

OBJECTIVE
The clinical relevance of the metabolically normal but obese phenotype for mortality risk is unclear. This study examines the risk for all-cause mortality in metabolically normal and abnormal obese (MNOB and MAOB, respectively) individuals.

RESEARCH DESIGN AND METHODS
The sample included 6,011 men and women from the Third National Health and Nutrition Examination Survey (NHANES III) with public-access mortality data linkage (follow-up = 8.7 ± 0.2 years; 292 deaths). Metabolically abnormal was defined as insulin resistance (IR) or two or more metabolic syndrome (MetSyn) criteria (excluding waist).

RESULTS
A total of 30% of obese subjects had IR, and 38.4% had two or more MetSyn factors, whereas only 6.0% (or 1.6% of the whole population) were free from both IR and all MetSyn factors. By MetSyn factors or IR alone, MNOB subjects (hazard ratio [HR]MetSyn 2.80 [1.18–6.65]; HRIR 2.58 [1.00–6.65]) and MAOB subjects (HRMetSyn 2.74 [1.46–5.15]; HRIR 3.09 [1.55–6.15]) had similar elevations in mortality risk compared with metabolically normal, normal weight subjects.

CONCLUSIONS
Although a rare phenotype, obesity, even in the absence of overt metabolic aberrations, is associated with increased all-cause mortality risk.
β-Cell–Mediated Signaling Predominates Over Direct α-Cell Signaling in the Regulation of Glucagon Secretion in Humans
Authors: Cooperberg Benjamin A. , Cryer Philip E. 
Published: September 2009

OBJECTIVE
Given evidence of both indirect and direct signaling, we tested the hypothesis that increased β-cell–mediated signaling of α-cells negates direct α-cell signaling in the regulation of glucagon secretion in humans.

RESEARCH DESIGN AND METHODS
We measured plasma glucagon concentrations before and after ingestion of a formula mixed meal and, on a separate occasion, ingestion of the sulfonylurea glimepiride in 24 basal insulin-infused, demonstrably β-cell–deficient patients with type 1 diabetes and 20 nondiabetic, demonstrably β-cell–sufficient individuals; the latter were infused with glucose to prevent hypoglycemia after glimepiride.

RESULTS
After the mixed meal, plasma glucagon concentrations increased from 22 ± 1 pmol/l (78 ± 4 pg/ml) to 30 ± 2 pmol/l (103 ± 7 pg/ml) in the patients with type 1 diabetes but were unchanged from 27 ± 1 pmol/l (93 ± 3 pg/ml) to 26 ± 1 pmol/l (89 ± 3 pg/ml) in the nondiabetic individuals (P &lt; 0.0001). After glimepiride, plasma glucagon concentrations increased from 24 ± 1 pmol/l (83 ± 4 pg/ml) to 26 ± 1 pmol/l (91 ± 4 pg/ml) in the patients with type 1 diabetes and decreased from 28 ± 1 pmol/l (97 ± 5 pg/ml) to 24 ± 1 pmol/l (82 ± 4 pg/ml) in the nondiabetic individuals (P &lt; 0.0001). Thus, in the presence of both β-cell and α-cell secretory stimuli (increased amino acid and glucose levels, a sulfonylurea) glucagon secretion was prevented when β-cell secretion was sufficient but not when β-cell secretion was deficient.

CONCLUSIONS
These data indicate that, among the array of signals, indirect reciprocal β-cell–mediated signaling predominates over direct α-cell signaling in the regulation of glucagon secretion in humans.
Aquaporin-1–mediated cerebral edema following traumatic brain injury: effects of acidosis and corticosteroid administration
Authors: Tran Nam D. , Kim Stefan , Vincent Heather K. , Rodriguez Anthony , Hinton David R. , Bullock M. Ross , Young Harold F. 
Published: September 2009

Object
Dysregulation of water homeostasis induces cerebral edema. Edema is a major cause of morbidity and mortality following traumatic brain injury (TBI). Aquaporin-1 (AQP-1), a water channel found in the brain, can function as a transporter for CO2 across the cellular membrane. Additionally, AQP-1's promoter contains a glucocorticoid response element. Thus, AQP-1 may be involved with edema-related brain injury and might be modulated by external conditions such as the pH and the presence of steroids. In this study, the authors investigated the hypotheses that: 1) AQP-1 participates in brain water homeostasis following TBI; 2) secondary injury (for example, acidosis) alters the expression of AQP-1 and exacerbates cerebral edema; and 3) corticosteroids augment brain AQP-1 expression and differentially affect cerebral edema under nonacidotic and acidotic conditions.

Methods
Anesthetized Sprague-Dawley rats were subjected to moderate to severe TBI (2.5–3.5 atm) or surgery without injury, and they were randomized to receive a 3-mg/kg bolus of intravenous dexamethasone within 10 minutes after injury or surgery, a 3-mg/kg bolus of dexamethasone followed by 1-mg/kg maintenance doses every 8 hours for 24 hours, or saline boluses at similar time intervals. A second group of animals was subjected to respiratory acidosis with target arterial blood pH 6.8–7.2 for 1 hour following the surgery or injury. To evaluate selective blockage of AQP-1, some animals received a single intraperitoneal dose of HgCl2 (0.3–30.0 mmol/L) within 30 minutes of injury or surgery. At 4 or 24 hours postinjury, animals were killed and their brains were harvested for mRNA, protein, or water content analyses.

Results
The authors demonstrated elevated cerebral edema levels at 4 and 24 hours following TBI. Dexamethasone administration within 1 hour of TBI attenuated the cerebral edema under nonacidotic conditions but worsened it under acidotic conditions. Selective blockage of AQP-1 channels with HgCl2 attenuated the edematous effects of corticosteroids and acidosis. Reverse transcriptase polymerase chain reaction and immunohistochemical analyses demonstrated a paucity of AQP-1 in the cerebral cortices of the uninjured animals. In contrast, AQP-1 mRNA and protein levels were higher in the cerebral cortices of animals that sustained a TBI.

Conclusions
These findings implicate an important, modifiable role for AQP-1 in water homeostasis within the CNS following TBI.
Long-term control of petroclival meningiomas through radiosurgery
Authors: Flannery Thomas J. , Kano Hideyuki , Lunsford L. Dade , Sirin Sait , Tormenti Matthew , Niranjan Ajay , Flickinger John C. , Kondziolka Douglas 
Published: September 2009

Object
Because of their critical location adjacent to brain, cranial nerve, and vascular structures, petroclival meningiomas remain a clinical challenge. The authors evaluated outcomes in 168 patients with petroclival meningiomas who underwent Gamma Knife surgery (GKS) during a 21-year interval.

Methods
Gamma Knife surgery was used as either primary or adjuvant treatment of 168 petroclival meningiomas involving the region between the petrous apex and the upper two-thirds of the clivus. The most common presenting symptoms were trigeminal nerve dysfunction, balance problems, diplopia, and hearing loss. The median tumor volume was 6.1 cm3 (range 0.3–32.5 cm3), and the median radiation dose to the tumor margin was 13 Gy (range 9–18 Gy).

Results
During a median follow-up of 72 months, neurological status improved in 44 patients (26%), remained stable in 98 (58%), and worsened in 26 (15%). Tumor volume decreased in 78 patients (46%), remained stable in 74 (44%), and increased in 16 (10%), all of whom were subjected to additional management strategies. Overall 5- and 10-year progression-free survival rates were 91 and 86%, respectively. Patients followed up for at least 10 years (31 patients) had tumor and symptom control rates of 97 and 94%, respectively. Eight patients had repeat radiosurgery, 4 underwent delayed resection, and 4 had fractionated radiation therapy. Cerebrospinal fluid diversion was performed in 7 patients (4%). Significant risk factors for tumor progression were a tumor volume ≥ 8 cm3 (p = 0.001) and male sex (p = 0.02).

Conclusions
In this 21-year experience, GKS for petroclival meningiomas obviated initial or further resection in 98% of patients and was associated with a low risk of adverse radiation effects. The authors believe that radiosurgery should be considered as an initial option for patients with smaller-volume, symptomatic petroclival meningiomas.
Kriging as an alternative for a more precise analysis of output parameters in nuclear safety—Large break LOCA calculation
Authors: Roustant Olivier , Joucla Jérôme , Probst Pierre 
Published: September 2009

AbstractThe methods using the best estimate codes are now applied in safety demonstration for nuclear power plants (NPP) to evaluate uncertainties of the relevant output parameters. Towards this objective, it is useful to further analyse the outputs, for example, to learn more about sensitivity to input parameters. In addition, this first analysis can be used to assess uncertainty. Such an analysis is difficult to obtain using the code itself because it is quite time‐consuming. One approach, called response surface methodology, consists in replacing the code by a simpler model, estimated with few runs. Linear regression is often used. In this paper, we propose kriging as introduced by Sacks et al. (Technometrics 1989; 31:41–47; Stat. Sci. 1989; 4(4):409–435) as an alternative.Kriging was applied to the Loss‐of‐Fluid Test (LOFT) loss of coolant experiment L2‐5, which was the subject of the former ISP 13 and the ongoing BEMUSE (ISP: International Standard Problem. BEMUSE: Best‐Estimate Methods–Uncertainty and Sensitivity Evaluation) international problem. The output is the second maximum peak cladding temperature (PCT) of the fuel. The best estimate code used is CATHARE2 V1.3L. We observe that kriging is more flexible and can handle irregularities. As a result, it gives more accurate predictions. In addition, sensitivity analysis is provided. This method offers complementary information and constructs a response surface more accurately, with a more realistic evaluation of risk. Copyright © 2009 John Wiley & Sons, Ltd.
Functional communication during signaled reinforcement and/or extinction
Authors: Jarmolowicz David P. , DeLeon Iser G. , Kuhn Stephanie A. Contrucci 
Published: September 2009

AbstractSchedule thinning following functional communication training (FCT) can increase treatment feasibility. Multiple‐schedule arrangements are often used in this process; however, the current literature provides little information on the optimum signal arrangements. In the current study, we examined the effects of three signal arrangements (i.e., signaled FR1, signaled EXT, and signaled FR1/EXT) on rates of problem behavior at dense schedule values and during schedule thinning. At all schedule values, signaled FR1/EXT controlled collateral behavior better than did signaled FR1 or signaled EXT. Additionally, for the single signal arrangements, the signaled FR1 was more efficient than the signaled EXT at dense schedules whereas the inverse was true at leaner schedules. Copyright © 2009 John Wiley & Sons, Ltd.