Range Of Activity Levels Research Articles

A 3D In Vitro Model of the Human Airway Epithelium Exposed to Tritiated Water: Dosimetric Estimate and Cytotoxic Effects.

Tritium has been receiving worldwide attention, particularly because of its production and use in existing fission reactors and future nuclear fusion technologies, leading to an increased risk of release in the environment. Linking human health effects to low-dose tritium exposures presents a challenge for many reasons. Among these: biological effects strongly depend on the speciation of tritiated products and exposure pathway; large dosimetric uncertainties may exist; measurements using in vitro cell cultures generally lack a description of effects at the tissue level, while large-scale animal studies might be ethically questionable and too highly demanding in terms of resources. In this context, three-dimensional models of the human airway epithelium are a powerful tool to investigate potential toxicity induced upon inhalation of radioactive products in controlled physiological conditions. In this study we exposed such a model to tritiated water (HTO) for 24 h, with a range of activity levels (up to ∼33 kBq µl-1 cm-2). After the exposures, we measured cell viability, integrity of epithelial layer and pro-inflammatory response at different post-exposure time-points. We also quantified tritium absorption and performed dosimetric estimates considering HTO passage through the epithelial layer, leading to reconstructed upper limits for the dose to the tissue of less than 50 cGy cumulative dose for the highest activity. Upon exposure to the highest activity, cell viability was not decreased; however, we observed a small effect on epithelial integrity and an inflammatory response persisting after seven days. These results represent a reference condition and will guide future experiments using human airway epithelium to investigate the effects of other peculiar tritiated products.

Algorithms, Filters And Corrections Compound Differences Between Multiple Lifestyle Physical Activity Estimates

Physical activity (PA) can be objectively and conveniently measured using accelerometers. The use of wrist-worn devices has grown dramatically over the past decade, becoming the preferred choice in many recreational, clinical and research applications. ActiGraph is a leading company in this field, wherein data from accelerometers can be analyzed in their ActiLife software. However, the effects of multiple algorithms, filters and corrections on PA outcomes are not always clear. PURPOSE: To examine how lifestyle PA estimates are impacted by multiple scoring methods in a commercial software platform. METHODS: We collected lifestyle wrist-worn accelerometer data (ActiGraph GT3X+) from 132 adults with a range of activity levels with and without chronic pain (low back pain, fibromyalgia, pain-free). We analyzed accelerations in ActiLife using multiple algorithms, with and without the wrist correction and proprietary low-frequency extension (LFE) across four PA domains: total EE (METs), active EE (kCal), MVPA time, and steps. Accelerometer and self-reported (International Physical Activity Questionnaire) PA outcomes were compared. RESULTS: PA estimates differed notably across most algorithms with highly variable, but typically large effect sizes (p < 0.05, median % change = 33.5% [6.9% – 62.6%], d = 1.04 [0.60 – 1.45]). The wrist correction reduced PA estimates across all outcomes (p < 0.05, % change = -15.0% [-3.9% – -31.8%], d = 0.56 [0.31 – 0.93]) save steps and one daily EE algorithm (no change). The LFE increased steps considerably (p < 0.05, % change = 72.3%, d = 1.44) yet had little effect across all other outcomes (p < 0.05, % change = 4.7% [2.9% – 4.9%], d = 0.13 [0.11 – 0.14]). Differences were always greater when multiple factors were considered (% change = 89.2% [80.7% – 201.3%]). Correlations between objective and self-reported PA were typically moderate (ρ = 0.55 [0.36 – 0.88]), were further reduced by the wrist correction, and affected minimally by the LFE. CONCLUSIONS: Previously-validated scoring methods are not necessarily interchangeable. The wrist correction and LFE inconsistently inflate PA estimates, with variability increasing when multiple factors are considered. Researchers should consistently report detailed methodology to optimize comparisons across studies and to normative guidelines.

A descriptive baseline analysis of the health of adults longitudinal observational (halo) study - the Australian cohort

Purpose: The Health of Adults’ Longitudinal Observational (HALO) Study explores the relationship between chronic disease and physical activity, in particular osteoarthritis (OA) and running. The study aims to disentangle the relationship between running and the development and progression of knee OA (KOA) among a general (non-elite) population across a range of activity levels and evaluate how risk factors such as volume of running and injury, impact on joint health. This analysis describes the original Australian baseline sample (n=250) collected for the HALO study in 2016.

Determining management preferences in a multimethod consumptive recreational fishery

Understanding behavioral responses of recreational fishers to management changes is fundamental for effective policy making. However, given the diverse motivations and nonmarket nature of recreational fishing, evaluating fishers’ preferences is nontrivial. This study examined fishers’ management preferences toward different management tools (i.e., a new measure or a change in the setting for an existing measure) in a highly consumptive recreational fishery. A combination of a discrete choice experiment and an opinion-based survey explored the potential heterogeneity in management preferences in the Tasmanian Rock Lobster fishery. Although the fishery has extensive management in place, further restrictions are required to limit recreational harvest in support of a strategy to achieve a stock rebuilding target. As a diverse fishery, with various fishing methods and a range of activity levels, it is expected that the perceptions of management changes vary across fisher subgroups. A phone survey was used to ask fishers’ opinions on how effective different management tools are at restricting catch and if they supported or opposed the tool. Additionally, a discrete choice experiment was used to assess if fishers’ utility is associated with a management tool and to what extent fishers are willing to trade a change in one management tool for a change in another. Results show that there are both homogenous and heterogeneous management preferences in the fishery across fisher subgroups. There was consensual aversion by all fisher subgroups toward changes in management settings that directly limit the catch of lobster, including a reduction in daily bag limit and shortened season length. Other changes to management settings, such as an increase in the minimum size limit, have less consensus in preference between fisher groups, and any changes in these tools could differentially impact fisher subgroups. The results from this research can support managers in identifying whether and to what extent intra-sector separation for the purposes of designing and implementing new management measures and settings is warranted, on the basis that it can increase effectiveness of achieving management and the likelihood of maximizing net utility within a fishery.

Activity time series of old stars from late F to early K

Context. A number of high-precision time series have recently become available for many stars as a result of data from CoRoT, Kepler, and TESS. These data have been widely used to study stellar activity. Photometry provides information that is integrated over the stellar disk. Therefore, there are many degeneracies between spots and plages or sizes and contrasts. In addition, it is important to relate activity indicators, derived from photometric light curves, to other indicators (Log R′HK and radial velocities). Aims. Our aim is to understand how to relate photometric variability to physical parameters in order to help the interpretation of these observations. Methods. We used a large number of synthetic time series of brightness variations for old main sequence stars within the F6-K4 range. Simultaneously, we computed using consistent modeling for radial velocity, astrometry, and chromospheric emission. We analyzed these time series to study the effect of the star spectral type on brightness variability, the relationship between brightness variability and chromospheric emission, and the interpretation of brightness variability as a function of spot and plage properties. We then studied spot-dominated or plage-dominated regimes. Results. We find that within our range of activity levels, the brightness variability increases toward low-mass stars, as suggested by Kepler results. However, many elements can create an interpretation bias. Brightness variability roughly correlates to Log R′HK level. There is, however, a large dispersion in this relationship, mostly caused by spot contrast and inclination. It is also directly related to the number of structures, and we show that it can not be interpreted solely in terms of spot sizes. Finally, a detailed analysis of its relation with Log R′HK shows that in the activity range of old main-sequence stars, we can obtain both spot or plage dominated regimes, as was shown by observations in previous works. The same star can also be observed in both regimes depending on inclination. Furthermore, only strong correlations between chromospheric emission and brightness variability are significant. Conclusions. Our realistic time series proves to be extremely useful when interpreting observations and understanding their limitations, most notably in terms of activity interpretation. Inclination is crucial and affects many properties, such as amplitudes and the respective role of spots and plages.

Relationship between body mass, lean mass, fat mass, and limb bone cross-sectional geometry: Implications for estimating body mass and physique from the skeleton.

ObjectivesEstimating body mass from skeletal dimensions is widely practiced, but methods for estimating its components (lean and fat mass) are poorly developed. The ability to estimate these characteristics would offer new insights into the evolution of body composition and its variation relative to past and present health. This study investigates the potential of long bone cross‐sectional properties as predictors of body, lean, and fat mass.Materials and MethodsHumerus, femur and tibia midshaft cross‐sectional properties were measured by peripheral quantitative computed tomography in sample of young adult women (n = 105) characterized by a range of activity levels. Body composition was estimated from bioimpedance analysis.ResultsLean mass correlated most strongly with both upper and lower limb bone properties (r values up to 0.74), while fat mass showed weak correlations (r ≤ 0.29). Estimation equations generated from tibial midshaft properties indicated that lean mass could be estimated relatively reliably, with some improvement using logged data and including bone length in the models (minimum standard error of estimate = 8.9%). Body mass prediction was less reliable and fat mass only poorly predicted (standard errors of estimate ≥11.9% and >33%, respectively).DiscussionLean mass can be predicted more reliably than body mass from limb bone cross‐sectional properties. The results highlight the potential for studying evolutionary trends in lean mass from skeletal remains, and have implications for understanding the relationship between bone morphology and body mass or composition.

The magnetic local time distribution of energetic electrons in the radiation belt region

AbstractUsing 14 years of electron flux data from the National Oceanic and Atmospheric Administration Polar Operational Environmental Satellites, a statistical study of the magnetic local time (MLT) distribution of the electron population is performed across a range of activity levels, defined by AE, AE*, Kp, solar wind velocity (Vsw), and VswBz. Three electron energies (&gt;30, &gt;100, and &gt;300 keV) are considered. Dawn‐dusk flux asymmetries larger than order of magnitude were observed for &gt;30 and &gt;100 keV electrons. For &gt;300 keV electrons, dawn‐dusk asymmetries were primarily due to a decrease in the average duskside flux beyond L* ∼ 4.5 that arose with increasing activity. For the &gt;30 keV population, substorm injections enhance the dawnside flux, which may not reach the duskside as the electrons can be on open drift paths and lost to the magnetopause. The asymmetries in the &gt;300 keV population are attributed to the combination of magnetopause shadowing and &gt;300 keV electron injections by large electric fields. We suggest that 3‐D radiation belt models could set the minimum energy boundary (Emin) to 30 keV or above at L* ∼ 6 during periods of low activity. However, for more moderate conditions, Emin should be larger than 100 keV and, for very extreme activities, ∼300 keV. Our observations show the extent that in situ electron flux readings may vary during active periods due to the MLT of the satellite and highlight the importance of 4‐D radiation belt models to fully understand radiation belt processes.

Investigation of secondary cooling design enhancements in thermally limited compact notebooks

Thermal design enhancements in a thermally limited compact notebook system are investigated in this paper. System temperature, power, and fan speed are characterized under a range of activity levels. A finite element model is developed, and validated against measurements. Design enhancements improve cooling with minimum intrusion to the existing mechanical design. A passive secondary heat pipe in the system reduces the CPU temperature by 5 $^{\circ}$C, and improves the system performance through increased CPU + Graphics and Memory Controller Hub (GMCH) thermal design power (TDP) by 6.4%. When such a secondary heat pipe is considered with an integrated off-the-shelf Peltier cooler, the CPU temperature is only reduced by 2.3 $^{\circ}$C and CPU+GMCH TDP is improved only by 4.9%. Although Peltier integration provides no benefit to thermals, it can be advantageous in generating small amount of thermoelectric power in conditions when the system is not executing thermally limited applications. Calculations suggest that a 10% increase in Seebeck coefficient and consequently a 5.5% increase in coefficient of performance (COP) of off-the-shelf thermoelectric materials can increase the TDP envelop by 7.1% using the Peltier-integrated secondary heat pipe scheme.

The effect of activation level on muscle function during locomotion: are optimal lengths and velocities always used?

Skeletal muscle exhibits broad functional diversity, despite its inherent length and velocity constraints. The observed variation in morphology and physiology is assumed to have evolved to allow muscle to operate at its optimal length and velocity during locomotion. Here, we used the variation in optimum lengths and velocities that occurs with muscle activation level to experimentally test this assumption. Muscle ergometry and sonomicrometry were used to characterize force-length and power-velocity relationships, and in vivo operating lengths and velocities, at a range of activation levels. Operating lengths and velocities were mapped onto activation level specific force-length and power-velocity relationships to determine whether they tracked changing optima. Operating velocities decreased in line with decreased optimal velocities, suggesting that optimal velocities are always used. However, operating lengths did not change with changing optima. At high activation levels, fibres used an optimal range of lengths. However, at lower activation levels, fibres appeared to operate on the ascending limb of sub-maximally activated force-length relationships. This suggests that optimal lengths are only used when demand is greatest. This study provides the first mapping of operating lengths to activation level-specific optima, and as such, provides insight into our assumptions about the factors that determine muscle performance during locomotion.

Prediction of performance reduction in self-paced exercise as modulated by the rating of perceived exertion.

Rating of perceived exertion (RPE) is a scale of exercise difficulty and has been hypothesized to be a regulator of work rate during self-pacing. The goal of this work was to develop a dynamic prediction of RPE and to characterize the control strategy employed to reduce work rate during self-paced exercise using RPE as feedback. Training and test data were acquired from the literature to develop a linear regression of RPE as a function of four physiological variables: core temperature, mean-weighted skin temperature, metabolic rate, and integral of relative oxygen consumption (R (2) = 0.85). A thermoregulatory model was used to predict core and mean-weighted skin temperature. Utilizing self-paced cycling and running data from the literature, we characterized reductions in work rate with a proportional-derivative control algorithm with RPE as feedback. Bland-Altman analysis revealed the necessity to parameterize RPE equations for untrained and endurance-trained individuals. Afterwards, dynamic predictions of RPE were accurate for a wide range of activity levels and air temperatures for walking, running, and cycling (LoA and bias of 2.3 and -0.03, respectively). For self-paced exercise, the control algorithm characterized the trend and magnitude of work rate reductions for cycling and running, and showed regulated RPE to be less conservative for shorter vs. longer duration exercise. A novel methodology to characterize self-paced work intensity, based upon dynamic physiologic response, is provided. The complete model is a useful tool that estimates performance decrements during self-paced exercise and predicts tolerance time for exhaustive fixed-rate exercise.

Abstract 2619: Meausuring PIP3 reveals the unexpected role of p110B in luminal breast cancers

Abstract The phosphatidylinositol 3-kinase (PI3K) family of lipid kinases plays a prominent role in the growth and survival of several types of cancer, including breast cancers where the PI3K pathway is altered in up to 70% of cases. Due to the technical challenges of measuring the PI3K product, PIP3 directly, the phosphorylation of the downstream effector AKT has historically been used to indirectly assess the activity of class I PI3K. While this approach has proven to be rather useful, it is based on the assumption that this readout is proportional to the levels of PIP3, which is likely to apply only to a limited range of activation levels and within specific contexts. Indeed, evaluation of the efficacy of PI3K inhibitors with such indirect measurements may approximate and oversimplify the complex transduction mechanism of PI3K. During time course experiments using the p110A selective inhibitor, BYL719, we observed that both PIP3 and p-AKT levels were similarly restored after 24 hours in HER2 amplified breast cancer cells, while the rebound of p-AKT was minimal and did not correlate with increased PIP3 levels in PIK3CA mutant breast cancer models. Both p110B inhibition and p110B depletion were effective in blocking the PIP3 rebound observed. Consistent with this, the combination of p110A and p110B inhibitors decreased cell growth and induced a better apoptotic response compared to BYL719 alone. We further demonstrated that only the combination of p110A and p110B inhibitors induced tumor regression. Importantly, PIP3 levels correlated with efficacy more reliably than p-AKT in a PIK3CA mutant model in vivo. These data suggest that measurement of PIP3 levels following treatment may serve as a more effective biomarker than p-AKT levels to predict response to PI3K inhibitors within this subset of breast cancers. Citation Format: Carlotta Costa, Hiromichi Ebi, Anthony C. Faber, Madhuri Nishtala, Youngchul Song, Cyril H. Benes, Jeffrey A. Engelman. Meausuring PIP3 reveals the unexpected role of p110B in luminal breast cancers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2619. doi:10.1158/1538-7445.AM2014-2619

Leisure Time Physical Activity of Moderate to Vigorous Intensity and Mortality: A Large Pooled Cohort Analysis

Leisure time physical activity reduces the risk of premature mortality, but the years of life expectancy gained at different levels remains unclear. Our objective was to determine the years of life gained after age 40 associated with various levels of physical activity, both overall and according to body mass index (BMI) groups, in a large pooled analysis. We examined the association of leisure time physical activity with mortality during follow-up in pooled data from six prospective cohort studies in the National Cancer Institute Cohort Consortium, comprising 654,827 individuals, 21-90 y of age. Physical activity was categorized by metabolic equivalent hours per week (MET-h/wk). Life expectancies and years of life gained/lost were calculated using direct adjusted survival curves (for participants 40+ years of age), with 95% confidence intervals (CIs) derived by bootstrap. The study includes a median 10 y of follow-up and 82,465 deaths. A physical activity level of 0.1-3.74 MET-h/wk, equivalent to brisk walking for up to 75 min/wk, was associated with a gain of 1.8 (95% CI: 1.6-2.0) y in life expectancy relative to no leisure time activity (0 MET-h/wk). Higher levels of physical activity were associated with greater gains in life expectancy, with a gain of 4.5 (95% CI: 4.3-4.7) y at the highest level (22.5+ MET-h/wk, equivalent to brisk walking for 450+ min/wk). Substantial gains were also observed in each BMI group. In joint analyses, being active (7.5+ MET-h/wk) and normal weight (BMI 18.5-24.9) was associated with a gain of 7.2 (95% CI: 6.5-7.9) y of life compared to being inactive (0 MET-h/wk) and obese (BMI 35.0+). A limitation was that physical activity and BMI were ascertained by self report. More leisure time physical activity was associated with longer life expectancy across a range of activity levels and BMI groups. Please see later in the article for the Editors' Summary.

Differences in activity level between cownose rays (Rhinoptera bonasus) and Atlantic stingrays (Dasyatis sabina) are related to differences in heart mass, hemoglobin concentration, and gill surface area

Aquatic animals are faced with the challenge of extracting oxygen from water, a medium that is metabolically expensive to ventilate and that contains just a fraction of the oxygen concentration relative to air, yet the physiologies of fishes have evolved to support a wide range of activity levels in nature. Oxygen delivery components, including gill surface area (oxygen uptake), blood chemistry (oxygen transport), and the heart (system pump), have been positively correlated to activity level in teleost fishes, yet relatively little is known about how these components are related to activity in elasmobranches. The current study addresses this question by examining heart mass, hemoglobin concentration, hematocrit level, and gill surface area in wild-caught representatives of the benthic Atlantic stingray (Dasyatis sabina) and active cownose ray (Rhinoptera bonasus). Allometric scaling exponents are similar for all four measures between the study species. Heart mass, gill surfaces areas, and hemoglobin concentrations were 2.1 times, approximately 7.1 times, and 2.0 times higher, respectively, in active cownose rays, when compared to benthic Atlantic stingrays, after correcting for differences in body mass. When considered in the context of functional plasticity within the oxygen delivery systems of benthic and active species, data from the current study indicate that higher activity levels in cownose rays are supported by modifications that, at least in part, are likely to enhance oxygen uptake.

Phenylmethylene hydantoins as prostate cancer invasion and migration inhibitors. CoMFA approach and QSAR analysis

Prostrate cancer constitutes the second leading cause of cancer deaths in men in United States. In the process of discovery of new antiproliferative and anti-metastatic agents against prostate cancer, marine-derived phenylmethylene hydantoin (PMH) derivatives were identified with activity level range between 50 and 200 μM. 3D-QSAR CoMFA model was used in virtual screening of commercially available derivatives of PMH. PMH derivatives with manifold increase in anti-migratory and anti-invasive activities were discovered using wound-healing and Cultrex invasion assays. Benzene ring replacement with other heterocyclic rings did not significantly improve the methylene hydantoins activities. Multivariate analysis performed on the whole series of methylene hydantoins, which further supported the findings of CoMFA model. Predictive QSAR model with conventional r 2 and cross-validated coefficient ( q 2) values up to 0.982 and 0.803 were established. The molecular volume (MV) and the log P were identified as critical parameters for methylene hydatoins migration inhibitory activity. PMH is a novel anti-metastatic lead class with potential therapeutic activity against prostate cancer.

Telomerase activity is not a key determinant of sensitivity to standard cytotoxic drugs in human esophageal carcinoma cell lines

The aim of the present study was to investigate if basal telomerase activity levels may predict sensitivity to cytotoxic drugs in a panel of human esophageal carcinoma cell lines. The TRAPeze telomerase detection assay was used to investigate telomerase activity in the cell lines. Cytotoxic drug sensitivity for 20 standard cytotoxic agents was assessed using the fluorometric microculture cytotoxicity assay (FMCA). Telomerase activity was detected in all cell lines with a broad range of activity levels. Drug sensitivity also varied considerably between the cell lines. Except for a P value towards a correlation between mitoxantrone and telomerase activity (P=0.054), no statistically significant correlation was found between telomerase activity levels and sensitivity to investigated drugs, including key drugs such as cisplatin (P=0.9), 5-fluorouracil (P=0.8) and doxorubicin (P=0.54). We therefore conclude that basal telomerase activity level is not a key determinant of sensitivity to standard cytotoxic drugs in esophageal carcinoma cell lines.

Apparatus for the Calibration/Certification of Direct Reading Tritium in Air Monitors

Direct reading tritium-in-air-monitors are widely used for immediate observation of discharges or working area levels where significant sources of tritium are held. These monitors require initial and periodic calibration certification at the levels likely to be encountered. We describe a purpose built gas handling apparatus which enables various activity levels of tritiated gas (3H + N2) to be precisely metered and circulated in a closed loop through the monitor under calibration at a wide range of activity levels.

Understanding falls in osteoporosis: The viscoelastic modeling perspective

Unsteadiness and increased postural sway predispose individuals with osteoporosis to falling. We examined this relationship from a biomechanical perspective using a viscoelastic model. Specifically, we investigated the center-of-pressure (COP) in quiet stance in 37 postmenopausal women (aged 42-79 years), diagnosed with osteopenia or osteoporosis and who engaged in a range of activity levels. Subjects stood on a force platform for two 20s intervals: one with eyes open (EO) and the other with eyes closed (EC). The COP signals were used to compute traditional measures of sway: standard deviation, range, and mean velocity. Based on the difference between the COP and its smoothed representation, we used the "COP minus center-of-mass" signal to compute selected properties of postural mechanics (stiffness and viscosity) and dynamics (frequency and damping) of stance. Sway variability and incidence of falls were not correlated even though our subjects displayed higher sway than age-matched subjects from other studies. Bone density was correlated with frequency in the mediolateral (ML) plane with EO (r=0.50, p<0.002). Irrespective of age, the decrease in postural frequency and increase in postural viscosity in the ML plane were determinants of imbalance and accounted for 18% and 8% of the variance, respectively. With EC, an additional 10% of the variance was contributed by the ML range. The increased ML viscosity was the sole predictor of falls accounting for 20% of the variance of the tendency to fall. Thus, ML frequency plays a fundamental role in preserving balance in that a low value is an important predictor of falls. Finally, although being physical activity may reduce sway, physical activity fails to improve poor postural strategies. To conclude, increases in viscosity and range elucidate further the unique strategy of ML body sway in individuals with osteopenia or osteoporosis and provide insight into how posture may be maintained by those who fear falling.

Fluctuations in Ankle Dorsiflexor Force are Similar in Young and Old Men and Women

0836 Force fluctuations during contractions of hand and leg muscles are often greater in old compared with young adults, but this variability has not been examined across a range of activation levels in muscles surrounding the ankle. PURPOSE: To compare the fluctuations in force during isometric contractions performed with the ankle dorsiflexor (AD) muscles in young and old adults. METHODS: Young (n = 10; 23 ± 3 yrs, 5 men, 5 women) and old (n = 11; 73 ± 5 yrs, 5 men, 6 women) healthy adults performed isometric maximum voluntary contractions (MVC's) and submaximal constant-force isometric contractions with the AD muscles at target forces of 2.5, 5, 10, 30, 50, and 80% of MVC. Subjects exerted the force as steadily as possible with visual feedback. The standard deviation (SD) and coefficient of variation (CV) of force were measured during constant-force segments of the submaximal trials. RESULTS: MVC force (N) was reduced in the old compared with the young subjects (196 ± 72 vs. 265 ± 94 N, P = 0.07). The SD of force increased with target force, as expected (from 0.35 N to 4.4 N for 2.5 – 80% MVC target forces). The CV of force was not significantly different between young and old adults for any target force level (P>0.05). The CV of force was not different between men and women in either age group (P>0.05). The CV of force was highest at 2.5% MVC (CV = 6.0%) and decreased to a minimum (CV = 2.0%) from 10–80% MVC (P<0.001), agreeing with previous findings on the effect of target force in hand and leg muscles. The dominant frequency of the force fluctuations was below 2 Hz. CONCLUSION: This data suggests that the neural factors responsible for the effect of target force on force fluctuations are similar between hand muscles, knee extensors, and AD muscles. Across a range of voluntary activation levels of the AD motor unit pool, the magnitude of fluctuations in motor output during isometric contractions is similar between young and old adults. Supported by AG19171 to BLT.

Modeled evidence of force reduction at the extensor carpi radialis brevis origin with the forearm support band

Purpose: Although the forearm support band has been hypothesized to reduce force and thus inflammation and degeneration at the extensor carpi radialis brevis (ECRB) origin, little evidence exists to support an actual effect. We present both a cadaveric and clinical model that show the effect and principles of the forearm support band. Method: The cadaver model measured forces at the ECRB origin as various pressures were applied to the forearm support band and while the ECRB tendon was loaded distally. For clinical correlation support band pressure during rest and activity was measured in healthy individuals. Results: Our results revealed an increased forearm support band effect with increased band pressure and a decreased relative effect with increased force applied distally. For clinical correlation the support band pressure during activity was measured in 21 healthy volunteers while controlling for the application pressure in 2 common support band designs. This resulted in activity pressures ranging from 43 to 192 mm Hg dependent on the starting pressure of application. Conclusions: Although further clinical evaluation is necessary to determine the most appropriate clinical indications and application pressures for the forearm support band these combined results suggest that the forearm support band may be most effective when applied to 30 to 50 mm Hg at rest, resulting in up to 120 mm Hg pressure during activity. According to our model this would result in a force reduction at the ECRB origin of approximately 13% to 15% throughout a range of activity levels. (J Hand Surg 2003;28A:279-287. Copyright © 2003 by the American Society for Surgery of the Hand.)

Recombinant human IgG molecules lacking Fcgamma receptor I binding and monocyte triggering activities.

Subclasses of human IgG have a range of activity levels with different effector systems but each triggers at least one mechanism of cell destruction. We are aiming to engineer non-destructive human IgG constant regions for therapeutic applications where depletion of cells bearing the target antigen is undesirable. The attributes required are a lack of killing via Fcgamma receptors (R) and complement but retention of neonatal FcR binding to maintain placental transport and the prolonged half-life of IgG. Eight variants of human IgG constant regions were made with anti-RhD and CD52 specificities. The mutations, in one or two key regions of the CH2 domain, were restricted to incorporation of motifs from other subclasses to minimize potential immunogenicity. IgG2 residues at positions 233 - 236, substituted into IgG1 and IgG4, reduced binding to FcgammaRI by 10(4)-fold and eliminated the human monocyte response to antibody-sensitized red blood cells, resulting in antibodies which blocked the functions of active antibodies. If glycine 236, which is deleted in IgG2, was restored to the IgG1 and IgG4 mutants, low levels of activity were observed. Introduction of the IgG4 residues at positions 327, 330 and 331 of IgG1 and IgG2 had no effect on FcgammaRI binding but caused a small decrease in monocyte triggering.