scholarly journals THU0540 A PHASE 2B STUDY OF INTRAVENOUSLY (IV) ADMINISTERED TC 99M TILMANOCEPT TO DETERMINE DIFFERENTIAL UPTAKE, REPRODUCIBILITY OVER TIME AND IMAGE STABILITY IN HEALTHY SUBJECTS AND IN PATIENTS WITH RHEUMATOID ARTHRITIS (RA) ON STABLE TREATMENT

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 509.2-510
Author(s):  
A. Hussein ◽  
D. Ralph ◽  
B. Potter ◽  
B. Abbruzzese ◽  
R. Hershey ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Joint Disease ◽  
Current Phase ◽  
Specific Reference ◽  
Activated Macrophages ◽  
Planar Imaging ◽  
Pixel Intensity ◽  
Cut Points ◽  
Over Time ◽  
Average Pixel Intensity

Background:At present, there are no reliable noninvasive means to directly monitor disease activity in RA patients. Activated macrophages are a critical component of the inflammatory etiology of RA due to their role in prolonged RA joint inflammation and destruction through the release of pro-inflammatory cytokines and chemokines. Tc 99m tilmanocept is a radiopharmaceutical imaging agent that binds with high affinity to the macrophage mannose receptor CD206 that resides on activated macrophages. Previous clinical trials demonstrated safety and tolerability of Tc 99m tilmanocept, as well as a determination of optimal clinical dose and timeframe for RA imaging.Objectives:The current phase 2b study aims to evaluate reproducibility and stability of imaging and will assess quantitative Tc 99m tilmanocept uptake cut points that reliably enable discrimination between joints of healthy people and RA patients.Methods:The analysis cohort contained 18 healthy controls (HC) clinically free of inflammatory joint disease and 12 subjects with clinically diagnosed RA who are on stable anti-inflammatory and/or anti-rheumatic therapy. Each subject received a 150-mcg dose of tilmanocept radiolabeled with 10 mCi of Tc 99m in a 3mL IV injection. Injection was followed by planar imaging at 60 and 180 minutes for both HC and RA subjects on study Day 0 and repeated in RA subjects on Day 8. Images were quantitatively assessed to detect localization within synovial spaces of bilateral hands and wrists by determining average pixel intensity in each region of interest relative to average pixel intensity in a joint-specific reference region.Results:Data obtained from the interim analysis support the hypothesis that Tc 99m tilmanocept imaging can provide robust quantitative imaging in HC and RA subjects. Repeat images within and between days demonstrate root mean squared differences that are approximately 10% or less of the observed localization of Tc 99m tilmanocept. Qualitatively, images of HC indicated no disease-related site-specific localization, whereas localization is present in RA subjects at levels expected given the difference in macrophage number and density in different pathotypes of RA. Notably, images from patients with active RA exhibit the same localization patterns on images taken in a test-retest fashion on the same day as well as in subjects with images acquired on Day 0 and Day 8 (see Figure 1). These results show low imaging readout variability, enabling reliable quantification of joints with RA-involved macrophage-mediated inflammation. Analysis of the HC and RA images was used to determine initial quantitative “cut-points” to differentiate between joints with and without the inflammation typically seen in RA.Figure 1.Tilmanocept consistently localizes in areas of macrophage-driven inflammation, demonstrating low variability. RA patients exhibit reproducible localization over a 1-week period. Typical of healthy subjects, no evidence of inflammation-related Tc 99m tilmanocept uptake was observed in the healthy control. Images on the right show same patient imaged on 2 different days.Conclusion:Tc 99m tilmanocept imaging of the joints in healthy subjects as well as in patients with active RA under stable treatment is reproducible and stable over time. The results confirmed that the signal in joints of healthy subjects and RA patients can be quantified and used to establish cut points to distinguish inflamed and non-inflamed joints on a joint-by-joint basis. These results provide the foundation for a noninvasive, objective method to monitor activity in macrophage-driven inflammation in joints of patients with RA.Disclosure of Interests:Ayah Hussein Employee of: Currently employed by Navidea Biopharmaceuticals, David Ralph Consultant of: Previous consultant for Navidea Biopharmaceuticals, Employee of: Currently employed by Navidea Biopharmaceuticals, Beth Potter Employee of: Currently employed by Navidea Biopharmaceuticals, Bonnie Abbruzzese Employee of: Currently employed by Navidea Biopharmaceuticals, Rachael Hershey Employee of: Currently employed by Navidea Biopharmaceuticals, Katherine Repp Employee of: Previously employed by Navidea Biopharmaceuticals, Haya Shakhtra Employee of: Currently employed by Navidea Biopharmaceuticals, Mehak Goel Employee of: Currently employed by Navidea Biopharmaceuticals, Madison Palmer Employee of: Currently employed by Navidea Biopharmaceuticals, Allison Kissling Employee of: Previously employed by Navidea Biopharmaceuticals, Carley Hartings Employee of: Previously employed by Navidea Biopharmaceuticals, Michael Blue Employee of: Currently employed by Navidea Biopharmaceuticals, Michael Rosol Employee of: Currently employed by Navidea Biopharmaceuticals

A Comparison of Near-Infrared Imaging and Computerized Tomography Scan for Detecting Maxillary Sinusitis

2021 ◽  
pp. 000348942110606
Author(s):  
Mehdi Abouzari ◽  
Brooke Sarna ◽  
Joon You ◽  
Adwight Risbud ◽  
Kotaro Tsutsumi ◽  
...  
Keyword(s):  
Maxillary Sinus ◽  
Computerized Tomography ◽  
Sensitivity And Specificity ◽  
Near Infrared ◽  
Maxillary Sinusitis ◽  
Tertiary Care ◽  
Pixel Intensity ◽  
Sinus Disease ◽  
Nir Imaging ◽  
Average Pixel Intensity

Objective: To investigate the use of near-infrared (NIR) imaging as a tool for outpatient clinicians to quickly and accurately assess for maxillary sinusitis and to characterize its accuracy compared to computerized tomography (CT) scan. Methods: In a prospective investigational study, NIR and CT images from 65 patients who presented to a tertiary care rhinology clinic were compared to determine the sensitivity and specificity of NIR as an imaging modality. Results: The sensitivity and specificity of NIR imaging in distinguishing normal versus maxillary sinus disease was found to be 90% and 84%, normal versus mild maxillary sinus disease to be 76% and 91%, and mild versus severe maxillary sinus disease to be 96% and 81%, respectively. The average pixel intensity was also calculated and compared to the modified Lund-Mackay scores from CT scans to assess the ability of NIR imaging to stratify the severity of maxillary sinus disease. Average pixel intensity over a region of interest was significantly different ( P < .001) between normal, mild, and severe disease, as well as when comparing normal versus mild ( P < .001, 95% CI 42.22-105.39), normal versus severe ( P < .001, 95% CI 119.43-174.14), and mild versus severe ( P < .001, 95% CI 41.39-104.56) maxillary sinus disease. Conclusion: Based on this data, NIR shows promise as a tool for identifying patients with potential maxillary sinus disease as well as providing information on severity of disease that may guide administration of appropriate treatments.

Do Radiographic Joint Damage and Disease Activity Influence Functional Disability Through Different Mechanisms? Direct and Indirect Effects of Disease Activity in Established Rheumatoid Arthritis

2013 ◽  
Vol 40 (9) ◽  
pp. 1505-1512 ◽  
Author(s):  
Sandhya C. Nair ◽  
Johannes W.J. Bijlsma ◽  
Jacobien H. van der Werf ◽  
Maaike J. van der Veen ◽  
Suzanne P. Linn-Rasker ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Functional Disability ◽  
Functional Decline ◽  
Joint Damage ◽  
Treatment Strategies ◽  
Joint Disease ◽  
Influence Functional ◽  
Over Time ◽  
Predictive Effect

Objective.To explore the relationship between rheumatoid arthritis (RA) disease activity and functional disability over time, considering indirect (predictive) and direct (concurrent) associations as well as the influence of radiographic joint damage and treatment strategy.Methods.Functional disability [Health Assessment Questionnaire (HAQ)], disease activity [28-joint Disease Activity Score (DAS28)], and radiographic joint damage [Sharp/van der Heijde score (SHS)] were measured in 4 consecutive randomized controlled trials with increasingly intensive (tight control) treatment strategies. Average followup time for the 3 cohorts was 97, 53, and 50 months, respectively. Next to current DAS28, the previous DAS28 was used to study the predictive effect of a change in DAS28 on progression of functional disability (HAQ). Finally, it was investigated whether SHS mediated the predictive effect of DAS28.Results.In patients treated with intensive treatment strategies, the progression of HAQ over time was statistically significantly less (p < 0.0001). The predictive influence of DAS28 on HAQ progression increased over the duration of the disease. SHS was not found to influence HAQ progression and did not mediate the predictive effect of DAS28. In the less intensively treated patients, the direct effect of disease activity decreased with disease duration, and contrarily, SHS did influence HAQ progression, but was not found to (fully) mediate the predictive effect of DAS28.Conclusion.In patients with RA treated with modern treatment strategies, there is less functional decline over time. Further, disease activity does predict functional decline but joint damage does not. This might indicate that factors associated with cumulative disease activity but not visible on radiographs can influence functional decline in patients with RA. This further underlines the importance of disease activity as a treatment target in early RA and in established RA.

scholarly journals Structural Health Monitoring for cultural heritage constructions: a resilience perspective

2019 ◽  
Author(s):  
Maria Pina Limongelli ◽  
Zehra Irem Turksezer ◽  
Pier Francesco Giordano
Keyword(s):  
Structural Health Monitoring ◽  
Cultural Heritage ◽  
Health Monitoring ◽  
Social Value ◽  
Specific Reference ◽  
Structural Health ◽  
Heritage Constructions ◽  
The Impact ◽  
Support Decision Making ◽  
Over Time

<p>Disturbances or disruptive events may induce reductions of functionality of the built environment. For Cultural Heritage (CH) structures, functionalities may range from technical, to economic ones linked to touristic activities, up to intangible functionalities related to the cultural and social value of these constructions. Resilience can be defined as the capability of a system overcome a disturbance with the minimum total loss of functionality over time. Structural Health Monitoring (SHM) may enhance resilience by providing information that can support decision making, aiming to reduce the impact of the disturbances. In this paper, the benefits of SHM systems as means for improving resilience of CH structures are addressed and discussed with specific reference to the three different decision situations; before, during and after events of disturbances. Examples of real applications of SHM for CH structures and its effect on the resilience of the system conclude the paper.</p>

scholarly journals Do Interference-Based Cut-Points Differentiate Mild, Moderate, and Severe Levels of 16 Cancer-Related Symptoms Over Time?

2009 ◽  
Vol 37 (2) ◽  
pp. 220-232 ◽  
Author(s):  
Sangchoon Jeon ◽  
Charles W. Given ◽  
Alla Sikorskii ◽  
Barbara Given
Keyword(s):  
Cut Points ◽  
Over Time

AB1239 THE EFFECT OF INFLUENZA VACCINATION ON THE MULTI-BIOMARKER DISEASE ACTIVITY SCORE AND ITS COMPONENT BIOMARKERS IN HEALTHY SUBJECTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1910-1911
Author(s):  
D. Furst ◽  
L. Lenz ◽  
M. Horton ◽  
D. Flake ◽  
E. Sasso ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza Vaccine ◽  
Disease Activity ◽  
Virus Vaccine ◽  
Healthy Subjects ◽  
Influenza Virus Vaccine ◽  
National Institutes Of Health ◽  
Research Support ◽  
Myriad Genetics ◽  
Over Time

Background:The multi-biomarker disease activity (MBDA) blood test measures 12 protein biomarkers (IL-6, CRP, SAA, EGF, VEGF, VCAM, MMP-1, MMP-3, leptin, resistin, TNF-RI and YKL40). It uses a validated algorithm to provide a score on a scale of 1-100 for assessing disease activity in patients with rheumatoid arthritis (RA). The MBDA score reflects several molecular aspects of inflammation, including cytokines, acute phase reactants, growth factors, molecular adhesion, metalloproteinases and hormones. Insights gained by understanding how vaccination affects these biomarkers in healthy subjects - in whom the level of inflammation prior to vaccination should be low and stable - may aid the understanding of how vaccination affects patients with RA.Objectives:The goal of this study was to understand how immunization of healthy subjects with the influenza vaccine affects the assessment of inflammation with the MBDA score and its 12 biomarkers.Methods:A 4-strain influenza virus vaccine (Fluarix Quadrivalent, GlaxoSmithKline) was administered intramuscularly to 22 healthy volunteer subjects on October 24, 2018. Serum samples were obtained immediately prior to vaccination (baseline) and 1, 2 and 3 weeks after vaccination. No restrictions were placed on subject activity. Samples were stored at -80oC until measurement of the 12 MBDA biomarkers for determination of the adjusted MBDA score, hereafter called the MBDA score. (Adjustment accounts for the effects of age, sex and adiposity1). MBDA scores (natural scale) and biomarker concentrations (log scale) were modeled using generalized estimating equations (GEE) that account for correlations between measurements from the same subject at multiple timepoints. Significance of MBDA score change or biomarker concentration change over time was determined by a likelihood ratio test of timepoints.Results:Of the 22 healthy subjects receiving the influenza virus vaccine, 14 (63.6%) were female, with mean (SD) age of 40.0 years (8.9). MBDA scores were low (<30), moderate (30-44) or high (>44) for 15 (68%), 6 (27%) and 1 (5%) subjects at baseline, and this distribution was stable over time (Figure 1). Overall, MBDA scores did not change significantly over time (p=0.48, Figure 2). Mean changes in MBDA score (95% CI) from baseline to weeks 1, 2 and 3 were 0.32 (-3.07, 3.71), 0.82 (-3.03, 4.67) and 2.86 (-1.10, 6.82), respectively (Figure 2); the week 3 value becomes 0.95 (-1.78, 3.68) if the week 3 outlier is removed. Among the 66 post-baseline measurements of change in MBDA score (Figure 2), 3 (5%) exceeded the 95% CI for change in MBDA score in this study (i.e., 14). When assessing the entire cohort across all timepoints, EGF was the only biomarker that demonstrated statistically significant change over time (p=5.6 x 10-7). At weeks 1, 2 and 3, the mean relative concentrations of EGF, compared with baseline, were 0.62 (0.52, 0.74), 0.86 (0.70, 1.06) and 0.62 (0.50, 0.76), respectively.Figure 1Figure 2Conclusion:Immunization of 22 healthy subjects with a quadrivalent influenza vaccine did not have a statistically significant effect on MBDA scores during a 3-week observation, and it had minimal effect on the component biomarkers.References:[1]Curtis et al.Rheumatology [Oxford]2018;58:874Disclosure of Interests:Daniel Furst Grant/research support from: AbbVie, Actelion, Amgen, BMS, Corbus Pharmaceuticals, the National Institutes of Health, Novartis, Pfizer, and Roche/Genentech, Consultant of: AbbVie, Actelion, Amgen, BMS, Cytori Therapeutics, Corbus Pharmaceuticals, the National Institutes of Health, Novartis, Pfizer, and Roche/Genentech, Speakers bureau: CMC Connect (McCann Health Company), Lauren Lenz Shareholder of: Myriad Genetics, Inc., Employee of: Myriad Genetics, Inc., Megan Horton Shareholder of: Myriad Genetics, Inc., Employee of: Myriad Genetics, Inc., Darl Flake Shareholder of: Myriad Genetics, Inc., Employee of: Myriad Genetics, Inc., Eric Sasso Shareholder of: Myriad Genetics, Inc., Employee of: Myriad Genetics, Inc., Michael E. Weinblatt Grant/research support from: BMS, Amgen, Lilly, Crescendo and Sonofi-Regeneron, Consultant of: Horizon Therapeutics, Bristol-Myers Squibb, Amgen, Abbvie, Crescendo, Lilly, Pfizer, Roche, Gilead

Abstract 10756: Chronic Kidney Disease in Long-term Survivors After Fontan Palliation

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Sheena Sharma ◽  
Rebecca L Ruebner ◽  
Susan L Furth ◽  
Kathryn M Dodds ◽  
Jack Rychik ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Function ◽  
Healthy Subjects ◽  
Single Ventricle ◽  
Fontan Operation ◽  
Long Term Survivors ◽  
Fontan Palliation ◽  
Over Time

Background: The Fontan operation is a palliative procedure for children with congenital single ventricle heart disease. With advances in prenatal diagnosis and surgical techniques, more children are surviving into adulthood with unique cardiovascular physiology. Little is currently known about long-term kidney function in these patients. Hypothesis: We hypothesize that long-term survivors after Fontan palliation will have a higher prevalence of chronic kidney disease (CKD) compared to healthy controls. Methods: We performed a retrospective cohort study of subjects evaluated through the Single Ventricle Survivorship Program (SVSP) at the Children’s Hospital of Philadelphia between July 1, 2010 and December 5, 2014 and healthy children similar in sex and age. The primary outcome was CKD, defined as eGFR <90 ml/min/1.73m2 calculated with age-appropriate estimating equations using creatinine and cystatin C. Secondary outcomes included proteinuria and hyperparathyroidism. Results: The Fontan cohort included 68 subjects with mean age of 13.9 years (SD 5.8) at SVSP visit who were 11.2 years (SD 5.7) from Fontan operation. The healthy cohort included 70 patients with mean age of 15.9 years (SD 3.9). Mean eGFR was 102.6 versus 101.9ml/min/1.73m2 (p=0.89) in pediatric Fontan versus healthy subjects using the complete CKiD equation, and 128.5 versus 129.7ml/min/1.73m2 (p=0.56) in adult Fontan versus healthy subjects using the CKD-EPI creatinine and cystatin formula. 10% of Fontan subjects had an eGFR<90 ml/min/1.73m2. Mean intact parathyroid hormone level was higher at 68.0pg/mL (SD 35.4) in the Fontan group compared to 26.0pg/mL (SD 13.6) in the healthy group. Proteinuria was found within 34% of the Fontan group compared to 4.6% within the control group. Conclusion: We found that 10% of subjects have eGFR <90ml/min/1.73m2 after Fontan palliation which would indicate CKD if this remained persistent over time. Although the majority of the cohort had normal kidney function by eGFR, we found a higher proportion with proteinuria and increased parathyroid hormone levels which may indicate early kidney disease. Future studies will focus on evaluating changes in kidney function over time in long-term survivors after Fontan palliation.

scholarly journals P737 Left ventricular hemodynamic forces: towards establishing reference values for healthy adults

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
F Capuano ◽  
R Cocchia ◽  
F Ferrara ◽  
S Lanero ◽  
V Russo ◽  
...  
Keyword(s):  
Reference Values ◽  
Healthy Subjects ◽  
Left Ventricular ◽  
Healthy Adults ◽  
Disease Assessment ◽  
Lv Function ◽  
Specific Reference ◽  
Endocardial Contour ◽  
Hemodynamic Forces ◽  
Lv Volume

Abstract Introduction Left ventricular hemodynamic forces (LV-HDF) have been recently demonstrated to be promising markers of sub-clinical dysfunction and potential predictors of disease outcome. However, there is a lack of reference values in healthy subjects. Knowledge of physiologic ranges is mandatory towards the use of LV-HDF-based indices for disease assessment in future clinical applications. Purpose Aim of the current study is to define the normal reference values for LV-HDF parameters in a large cohort of healthy adults. Here we present preliminary results for the initial set of enrolled subjects. Methods We enrolled 82 healthy subjects [mean age 44 ± 13.2 years (range 18-88), 41 men]. All participants underwent standard transthoracic echocardiography (TTE) examination, as recommended by current guidelines, including apical two-, three- and four-chamber windows, acquired at a frame rate above 40 Hz. These were then analyzed by tri-plane tissue tracking, measuring LV volume and LV ejection fraction (EF) as reference parameters. The same tracking method was used to evaluate the global hemodynamic force by a novel mathematical calculation technique applied to the three-dimensional endocardial contour. Physical-based LV-HDF parameters were then extracted for clinical application; these included the amplitude (root mean square) of the longitudinal and transversal force components (FL and FT) and their alignment angle relative to the LV axis. Parameters were computed as average over the whole cardiac cycle as well as limited to the systolic phase. Forces were normalized with LV volume to reduce variability with LV dimension, and divided by specific weight to yield a dimensionless measure. Results Mean EF was 63 ± 9%. Whole cycle LV-HDF parameters were: FL = 16.0 ± 5.6%, FT = 2.3 ± 0.8%, with significant longitudinal alignment FT/FL = 0.15 ± 0.04, angle = 13.0°±3.1°. Systolic HDF parameters were: FL = 22.7 ± 8.2%, FT = 2.9 ± 1.1%, with longitudinal alignment FT/FL = 0.13 ± 0.04, angle = 11.2°±3.1°. Importantly, dimensionless physical-based LV-HDF parameters showed no significant variation with age, gender or BSA. Conclusions We report the physiologic range of LV-HDF parameters measured by TTE. Knowledge of age- and gender-specific reference values, for a combination of standard, mechanical and hemodynamic indices, can improve the global assessment of the LV function and may help to detect sub-clinical stages of LV dysfunction.

scholarly journals Veld management with specific reference to game ranching in the grassland and savanna areas of South Africa

Koedoe ◽  
1990 ◽  
Vol 33 (2) ◽  
Author(s):  
W.S.W. Trollope
Keyword(s):  
South Africa ◽  
Land Use ◽  
Nature Conservation ◽  
National Parks ◽  
Management Practices ◽  
Wide Spectrum ◽  
Management Program ◽  
Specific Reference ◽  
Game Ranching ◽  
Over Time

Veld management refers to the management of natural vegetation for specific objectives related to different forms of land use. In the wildlife context a wide spectrum of different forms of land use are practised ranging from pure nature conservation in large national parks through to smaller areas used for game farming. Consequently the products useable to society emanating from these areas vary greatly, and therefore the management of veld stocked with wildlife is extremely complex and must be adapted to the particular form of land use that is being practised. A generally accepted principle is that the smaller the area being used for wildlife the more intensively it must be managed, particularly game ranches. A prerequisite for the development of an effective veld management program is a comprehensive assessment of the condition of the veld upon which realistic veld management practices can be formulated. These practices will include stocking the veld with the appropriate species and numbers of animals, grazing and browsing management, veld burning and the provision of watering points. Finally a programme for monitoring veld condition over time is a prerequisite for sound veld management.

scholarly journals Population Pharmacokinetic Modeling of VL-2397, a Novel Systemic Antifungal Agent: Analysis of a Single- and Multiple-Ascending-Dose Study in Healthy Subjects

2019 ◽  
Vol 63 (6) ◽  
Author(s):  
Laura L. Kovanda ◽  
Sean M. Sullivan ◽  
Larry R. Smith ◽  
Amit V. Desai ◽  
Pete L. Bonate ◽  
...  
Keyword(s):  
Antifungal Agent ◽  
Healthy Subjects ◽  
Phase 1 ◽  
Plasma Concentrations ◽  
Population Pharmacokinetic ◽  
Binding Model ◽  
Saturable Binding ◽  
Drug Concentrations ◽  
Over Time

ABSTRACT VL-2397, a novel, systemic antifungal agent, has potent in vitro and in vivo fungicidal activity against Aspergillus species. Plasma concentrations from a phase 1 study were used to construct a population pharmacokinetic (PPK) model for VL-2397. Healthy subjects aged 18 to 55 years received single doses of VL-2397, ranging from 3 to 1,200 mg, multiple daily doses of 300, 600, or 1,200 mg for 7 days, or 300 mg three times/day for 7 days followed by 600 mg daily for 21 days. Plasma samples were collected throughout the dosing intervals. Sixty-six subjects provided 1,908 concentrations. Drug concentrations over time were increased less than dose proportionally for doses above 30 mg. Dose-normalized concentrations plotted over time did not overlap. A 3-compartment nonlinear saturable binding model fit the data well. Clearance increased with dose, and mean values ranged from 0.4 liters/h at 3 mg to 8.5 liters/h at 1,200 mg. Mean volume in the central compartment ranged from 4.8 to 6.9 liters across doses. In the first 24 h, once-daily dosing results in a rapid decrease in concentrations by hour 16 to approximately 1 mg/liter, regardless of dose, with slow clearance over time. Administration of 300 mg every 8 h achieved concentrations above 1 mg/liter over an entire 24-h period. There was a significant relationship between body surface area and clearance. The data suggest that VL-2397 has nonlinear saturable binding kinetics. Protein binding is the likely primary source of the nonlinearity. The PPK model can now be used to optimize dosing by bridging the kinetics to efficacious pharmacodynamic targets.

scholarly journals Using Accelerometers in Youth Physical Activity Studies: A Review of Methods

2013 ◽  
Vol 10 (3) ◽  
pp. 437-450 ◽  
Author(s):  
Kelli L. Cain ◽  
James F. Sallis ◽  
Terry L. Conway ◽  
Delfien Van Dyck ◽  
Lynn Calhoon
Keyword(s):  
Physical Activity ◽  
Decision Rule ◽  
Decision Rules ◽  
Moderate Intensity ◽  
Accelerometer Data ◽  
Cut Points ◽  
Moderate Intensity Physical Activity ◽  
Youth Physical Activity ◽  
Intensity Physical Activity ◽  
Over Time

Background:In 2005, investigators convened by the National Cancer Institute recommended development of standardized protocols for accelerometer use and reporting decision rules in articles. A literature review was conducted to document accelerometer methods and decision rule reporting in youth physical activity articles from 2005−2010.Methods:Nine electronic databases identified 273 articles that measured physical activity and/or sedentary behavior using the most-used brand of accelerometer (ActiGraph). Six key methods were summarized by age group (preschool, children, and adolescents) and trends over time were examined.Results:Studies using accelerometers more than doubled from 2005−2010. Methods included 2 ActiGraph models, 6 epoch lengths, 6 nonwear definitions, 13 valid day definitions, 8 minimum wearing day thresholds, 12 moderate-intensity physical activity cut points, and 11 sedentary cut points. Child studies showed the most variation in methods and a trend toward more variability in cut points over time. Decision rule reporting improved, but only 54% of papers reported on all methods.Conclusion:The increasing diversity of methods used to process and score accelerometer data for youth precludes comparison of results across studies. Decision rule reporting is inconsistent, and trends indicate declining standardization of methods. A methodological research agenda and consensus process are proposed.

Sign in / Sign up

Export Citation Format

Share Document