Modeling Electrically Active Viscoelastic Membranes

The membrane protein prestin is native to the cochlear outer hair cell that is crucial to the ear's amplification and frequency selectivity throughout the whole acoustic frequency range. The outer hair cell exhibits interrelated dimensional changes, force generation, and electric charge transfer. Cells transfected with prestin acquire unique active properties similar to those in the native cell that have also been useful in understanding the process. Here we propose a model describing the major electromechanical features of such active membranes. The model derived from thermodynamic principles is in the form of integral relationships between the history of voltage and membrane resultants as independent variables and the charge density and strains as dependent variables. The proposed model is applied to the analysis of an active force produced by the outer hair cell in response to a harmonic electric field. Our analysis reveals the mechanism of the outer hair cell active (isometric) force having an almost constant amplitude and phase up to 80 kHz. We found that the frequency-invariance of the force is a result of interplay between the electrical filtering associated with prestin and power law viscoelasticity of the surrounding membrane. Paradoxically, the membrane viscoelasticity boosts the force balancing the electrical filtering effect. We also consider various modes of electromechanical coupling in membrane with prestin associated with mechanical perturbations in the cell. We consider pressure or strains applied step-wise or at a constant rate and compute the time course of the resulting electric charge. The results obtained here are important for the analysis of electromechanical properties of membranes, cells, and biological materials as well as for a better understanding of the mechanism of hearing and the role of the protein prestin in this mechanism

Power efficiency of outer hair cell somatic electromotility

© 2009 Rabbitt et al. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS Computational Biology 5 (2009): e1000444, doi:10.1371/journal.pcbi.1000444.Cochlear outer hair cells (OHCs) are fast biological motors that serve to enhance the vibration of the organ of Corti and increase the sensitivity of the inner ear to sound. Exactly how OHCs produce useful mechanical power at auditory frequencies, given their intrinsic biophysical properties, has been a subject of considerable debate. To address this we formulated a mathematical model of the OHC based on first principles and analyzed the power conversion efficiency in the frequency domain. The model includes a mixture-composite constitutive model of the active lateral wall and spatially distributed electro-mechanical fields. The analysis predicts that: 1) the peak power efficiency is likely to be tuned to a specific frequency, dependent upon OHC length, and this tuning may contribute to the place principle and frequency selectivity in the cochlea; 2) the OHC power output can be detuned and attenuated by increasing the basal conductance of the cell, a parameter likely controlled by the brain via the efferent system; and 3) power output efficiency is limited by mechanical properties of the load, thus suggesting that impedance of the organ of Corti may be matched regionally to the OHC. The high power efficiency, tuning, and efferent control of outer hair cells are the direct result of biophysical properties of the cells, thus providing the physical basis for the remarkable sensitivity and selectivity of hearing.This work was supported by NIDCD R01 DC04928 (Rabbitt), NIDCD R01 DC00384 (Brownell) and NASA Ames GSRA56000135 (Breneman)

Understanding adolescent and young adult use of family physician services: a cross-sectional analysis of the Canadian Community Health Survey

BACKGROUND: Primary health care is known to have positive effects on population health and may reduce at-risk behavior and health problems in adolescence. Yet little is known about the factors that are associated with adolescent and young adult utilization of family physician services. It is critical to determine the factors associated with utilization to inform effective primary health care policy. We address this gap in the primary health care literature by examining three issues concerning adolescent and young adult family physician use: inequity; the unique developmental stage of adolescence; and the distinction between utilization (users versus non-users) and intensity (high users versus low users). METHODS: We conducted nested logistic regressions for two outcomes: utilization and intensity of family physician services for early adolescence, middle adolescence, and young adulthood using the 2005 Canadian Community Health Survey. RESULTS: Chronic conditions were associated with utilization in early and middle adolescence and intensity in all age groups. Respondents from Quebec had lower odds of utilization. Those without a regular medical doctor had much lower odds of being users. The factors associated with use in early and middle adolescence were in keeping with parental involvement while the factors in young adulthood show the emerging independence of this group. CONCLUSIONS: We highlight key messages not known previously for adolescent and young adult use of family physician services. There is inequity concerning regional variation and for those who do not have a regular medical doctor. There is variation in factors associated with family physician services across the three age groups of adolescence. Health care and health care policies aimed at younger adolescents must consider that parents are still the primary decision-maker while older adolescents are more autonomous. There is variation in the factors associated with the two outcomes of utilization and intensity of services. Factors associated with utilization must be understood when considering the equitability of access to primary health care while factors associated with intensity must be understood when considering appropriate use of resources. The understanding gained from this study can inform health care policy that is responsive to the critical developmental stage of adolescence and young adulthood

Avoidable mortality across Canada from 1975 to 1999

BACKGROUND: The concept of 'avoidable' mortality (AM) has been proposed as a performance measure of health care systems. In this study we examined mortality in five geographic regions of Canada from 1975 to 1999 for previously defined avoidable disease groups that are amenable to medical care and public health. These trends were compared to mortality from other causes. METHODS: National and regional age-standardized mortality rates for ages less than 65 years were estimated for avoidable and other causes of death for consecutive periods (1975–1979, 1980–1985, 1985–1989, 1990–1994, and 1995–1999). The proportion of all-cause mortality attributable to avoidable causes was also determined. RESULTS: From 1975–1979 to 1995–1999, the AM decrease (46.9%) was more pronounced compared to mortality from other causes (24.9%). There were persistent regional AM differences, with consistently lower AM in Ontario and British Columbia compared to the Atlantic, Quebec, and Prairies regions. This trend was not apparent when mortality from other causes was examined. Injuries, ischaemic heart disease, and lung cancer strongly influenced the overall AM trends. CONCLUSION: The regional differences in mortality for ages less than 65 years was attributable to causes of death amenable to medical care and public health, especially from causes responsive to public health

124I-HuCC49deltaCH2 for TAG-72 antigen-directed positron emission tomography (PET) imaging of LS174T colon adenocarcinoma tumor implants in xenograft mice: preliminary results

<p>Abstract</p> <p>Background</p> <p>¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG-PET) is widely used in diagnostic cancer imaging. However, the use of ¹⁸F-FDG in PET-based imaging is limited by its specificity and sensitivity. In contrast, anti-TAG (tumor associated glycoprotein)-72 monoclonal antibodies are highly specific for binding to a variety of adenocarcinomas, including colorectal cancer. The aim of this preliminary study was to evaluate a complimentary determining region (CDR)-grafted humanized C_H2-domain-deleted anti-TAG-72 monoclonal antibody (HuCC49deltaC_H2), radiolabeled with iodine-124 (¹²⁴I), as an antigen-directed and cancer-specific targeting agent for PET-based imaging.</p> <p>Methods</p> <p>HuCC49deltaC_H2 was radiolabeled with ¹²⁴I. Subcutaneous tumor implants of LS174T colon adenocarcinoma cells, which express TAG-72 antigen, were grown on athymic Nu/Nu nude mice as the xenograft model. Intravascular (i.v.) and intraperitoneal (i.p.) administration of ¹²⁴I-HuCC49deltaC_H2 was then evaluated in this xenograft mouse model at various time points from approximately 1 hour to 24 hours after injection using microPET imaging. This was compared to i.v. injection of ¹⁸F-FDG in the same xenograft mouse model using microPET imaging at 50 minutes after injection.</p> <p>Results</p> <p>At approximately 1 hour after i.v. injection, ¹²⁴I-HuCC49deltaC_H2 was distributed within the systemic circulation, while at approximately 1 hour after i.p. injection, ¹²⁴I-HuCC49deltaC_H2 was distributed within the peritoneal cavity. At time points from 18 hours to 24 hours after i.v. and i.p. injection, ¹²⁴I-HuCC49deltaC_H2 demonstrated a significantly increased level of specific localization to LS174T tumor implants (p = 0.001) when compared to the 1 hour images. In contrast, approximately 50 minutes after i.v. injection, ¹⁸F-FDG failed to demonstrate any increased level of specific localization to a LS174T tumor implant, but showed the propensity toward more nonspecific uptake within the heart, Harderian glands of the bony orbits of the eyes, brown fat of the posterior neck, kidneys, and bladder.</p> <p>Conclusions</p> <p>On microPET imaging, ¹²⁴I-HuCC49deltaC_H2 demonstrates an increased level of specific localization to tumor implants of LS174T colon adenocarcinoma cells in the xenograft mouse model on delayed imaging, while ¹⁸F-FDG failed to demonstrate this. The antigen-directed and cancer-specific ¹²⁴I-radiolabled anti-TAG-72 monoclonal antibody conjugate, ¹²⁴I-HuCC49deltaC_H2, holds future potential for use in human clinical trials for preoperative, intraoperative, and postoperative PET-based imaging strategies, including fused-modality PET-based imaging platforms.</p

Estimates of abundance and trend on a Blue Whale feeding ground off Isla de Chiloé, Chile

Since 1970, blue whales (Balaenoptera musculus) have been seen feeding in the waters off southern Chile during the summer and autumn (December to May). Investigation of the genetic, acoustic and morphological characteristics of these blue whales shows that they are a distinct but unnamed subspecies, called the Chilean blue whales. Photo-identification surveys have been conducted in the waters off northwestern Isla Grande de Chiloé, southern Chile from 2004–2012 and Isla Chañaral, central Chile in 2012. Over this time, 1,070 blue whales were encountered yielding, after photo-quality control, 318 and 267 unique photographs of the left and right side of the flank respectively. Using mark-recapture analysis of left and right side photographs collected from Isla Grande de Chiloé (2004–2012), open population models estimate that ~570–760 whales are feeding seasonally in this region. POPAN superpopulation abundance estimates for the same feeding ground in 2012 are 762 (95% confidence intervals, CI = 638–933) and 570 (95% CI 475–705) for left and right side datasets respectively, very similar to results from closed population models. Estimates of trend revealed strong variation in abundance, peaking in 2009 and [suggesting] fluctuating use in the survey area over time, likely related to the density of their prey. High inter-annual return rates suggest a degree of site-fidelity of individuals to Isla Grande de Chiloé and that the number of whales using this feeding ground is relatively small