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The cervix shortens and softens as its collagen microstructure remodels in preparation for birth. Altered cervical tissue collagen microstructure can contribute to a mechanically weak cervix and premature cervical dilation and delivery. To investigate the local microstructural changes associated with anatomic location and pregnancy, we used second-harmonic generation microscopy to quantify the orientation and spatial distribution of collagen throughout cervical tissue from 4 pregnant and 14 non-pregnant women. Across patients, the alignment and concentration of collagen within the cervix was more variable near the internal os and less variable near the external os. Across anatomic locations, the spatial distribution of collagen within a radial zone adjacent to the inner canal of the cervix was more homogeneous than that of a region comprising the middle and outer radial zones. Two regions with different collagen distribution characteristics were found. The anterior and posterior sections in the outer radial zone were characterized by greater spatial heterogeneity of collagen than that of the rest of the sections. Our findings suggest that the microstructural alignment and distribution of collagen varies with anatomic location within the human cervix. These observed differences in collagen microstructural alignment may reflect local anatomic differences in cervical mechanical loading and function. Our study deepens the understanding of specific microstructural cervical changes in pregnancy and informs investigations of potential mechanisms for normal and premature cervical remodeling., (© 2018 Society for Reproduction and Fertility.)

The mechanical integrity of the soft tissue structures supporting the fetus may play a role in maintaining a healthy pregnancy and triggering the onset of labor. Currently, the level of mechanical loading on the uterus, cervix, and fetal membranes during pregnancy is unknown, and it is hypothesized that the over-stretch of these tissues contributes to the premature onset of contractility, tissue remodeling, and membrane rupture, leading to preterm birth. The purpose of this review article is to introduce and discuss engineering analysis tools to evaluate and predict the mechanical loads on the uterus, cervix, and fetal membranes. Here we will explore the potential of using computational biomechanics and finite element analysis to study the causes of preterm birth and to develop a diagnostic tool that can predict gestational outcome. We will define engineering terms and identify the potential engineering variables that could be used to signal an abnormal pregnancy. We will discuss the translational ability of computational models for the better management of clinical patients. We will also discuss the process of model validation and the limitations of these models. We will explore how we can borrow from parallel engineering fields to push the boundary of patient care so that we can work toward eliminating preterm birth., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Preterm birth is the leading cause of neonatal mortality and morbidity worldwide. Spontaneous preterm birth is a complex, multifactorial condition in which cervical dysfunction plays an important role in some women. Current treatment options for cervical dysfunction include cerclage and supplemental progesterone. In addition, cervical pessary is being studied in research protocols. However, cerclage, supplemental progesterone and cervical pessary have well known limitations and there is a strong need for alternate treatment options. In this review, we discuss two novel interventions to treat cervical dysfunction: (1) injectable, silk protein-based biomaterials for cervical tissue augmentation (injectable cerclage) and (2) a patient-specific pessary. Three-dimensional computer simulation of the cervix is performed to provide a biomechanical rationale for the interventions. Further development of these novel interventions could lead to new treatment options for women with cervical dysfunction., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The appropriate biomechanical function of the uterus is required for the execution of human reproduction. These functions range from aiding the transport of the embryo to the implantation site, to remodeling its tissue walls to host the placenta, to protecting the fetus during gestation, to contracting forcefully for a safe parturition and postpartum, to remodeling back to its nonpregnant condition to renew the cycle of menstruation. To serve these remarkably diverse functions, the uterus is optimally geared with evolving and contractile muscle and tissue layers that are cued by chemical, hormonal, electrical, and mechanical signals. The relationship between these highly active biological signaling mechanisms and uterine biomechanical function is not completely understood for normal reproductive processes and pathological conditions such as adenomyosis, endometriosis, infertility and preterm labor. Animal studies have illuminated the rich structural function of the uterus, particularly in pregnancy. In humans, medical imaging techniques in ultrasound and magnetic resonance have been combined with computational engineering techniques to characterize the uterus in vivo, and advanced experimental techniques have explored uterine function using ex vivo tissue samples. The collective evidence presented in this review gives an overall perspective on uterine biomechanics related to both its nonpregnant and pregnant function, highlighting open research topics in the field. Additionally, uterine disease and infertility are discussed in the context of tissue injury and repair processes and the role of computational modeling in uncovering etiologies of disease. WIREs Syst Biol Med 2017, 9:e1388. doi: 10.1002/wsbm.1388 For further resources related to this article, please visit the WIREs website., (© 2017 Wiley Periodicals, Inc.)

The extracellular matrix (ECM) plays an active and dynamic role that both reflects and facilitates the functional requirements of a tissue. The mature ECM of the nonpregnant cervix is drastically reorganized during pregnancy to drive changes in tissue mechanics that ensure safe birth. In this study, our research on mice deficient in the proteoglycan decorin have led to the finding that progesterone and estrogen play distinct and complementary roles to orchestrate structural reorganization of both collagen and elastic fibers in the cervix during pregnancy. Abnormalities in collagen and elastic fiber structure and tissue mechanical function evident in the cervix of nonpregnant and early pregnant decorin-null mice transiently recover for the remainder of pregnancy only to return 1 month postpartum. Consistent with the hypothesis that pregnancy levels of progesterone and estrogen may regulate ECM organization and turnover, expressions of factors required for assembly and synthesis of collagen and elastic fibers are temporally regulated, and the ultrastructure of collagen fibrils and elastic fibers is markedly altered during pregnancy in wild-type mice. Finally, utilizing ovariectomized nonpregnant decorin-null mice, we demonstrate structural resolution of collagen and elastic fibers by progesterone or estrogen, respectively, and the potential for both ECM proteins to contribute to mechanical function. These investigations advance understanding of regulatory factors that drive specialized ECM organization and contribute to an understanding of the cervical remodeling process, which may provide insight into potential complications associated with preterm birth that impact 9.6% of live births in the United States., (Copyright © 2017 Endocrine Society.)

Background: Premature cervical remodeling resulting in spontaneous preterm birth may begin with premature failure or relaxation at the internal os (termed "funneling"). To date, we do not understand why the internal os fails or why funneling occurs in some cases of premature cervical remodeling. Although the human cervix is thought to be mostly collagen with minimal cellular content, cervical smooth muscle cells are present in the cervix and can cause cervical tissue contractility., Objective: To understand why the internal os relaxes or why funneling occurs in some cases of premature cervical remodeling, we sought to evaluate cervical smooth muscle cell content and distribution throughout human cervix and correlate if cervical smooth muscle organization influences regional cervical tissue contractility., Study Design: Using institutional review board-approved protocols, nonpregnant women <50 years old undergoing hysterectomy for benign indications were consented. Cervical tissue from the internal and external os were immunostained for smooth muscle cell markers (α-smooth muscle actin, smooth muscle protein 22 calponin) and contraction-associated proteins (connexin 43, cyclooxygenase-2, oxytocin receptor). To evaluate cervical smooth muscle cell morphology throughout the entire cervix, whole cervical slices were obtained from the internal os, midcervix, and external os and immunostained with smooth muscle actin. To correlate tissue structure with function, whole slices from the internal and external os were stimulated to contract with 1 μmol/L of oxytocin in organ baths. In separate samples, we tested if the cervix responds to a common tocolytic, nifedipine. Cervical slices from the internal os were treated with oxytocin alone or oxytocin + increasing doses of nifedipine to generate a dose response and half maximal inhibitory concentration. Student t test was used where appropriate., Results: Cervical tissue was collected from 41 women. Immunohistochemistry showed cervical smooth muscle cells at the internal and external os expressed mature smooth muscle cell markers and contraction-associated proteins. The cervix exhibited a gradient of cervical smooth muscle cells. The area of the internal os contained 50-60% cervical smooth muscle cells that were circumferentially organized in the periphery of the stroma, which may resemble a sphincter-like pattern. The external os contained approximately 10% cervical smooth muscle cells that were randomly scattered in the tissue. In organ bath studies, oxytocin stimulated the internal os to contract with more than double the force of the external os (1341 ± 693 vs 523 ± 536 integrated grams × seconds, respectively, P = .009). Nifedipine significantly decreased cervical tissue muscle force compared to timed vehicle control (oxytocin alone) at doses of 10(-5) mol/L (vehicle 47% ± 15% vs oxytocin + nifedipine 24% ± 16%, P = .007), 10(-4) mol/L (vehicle 46% ± 16% vs oxytocin + nifedipine -4% ± 20%, P = .003), and 10(-3) mol/L (vehicle 42% ± 14% vs oxytocin + nifedipine -15% ± 18%, P = .0006). The half maximal inhibitory concentration for nifedipine was 1.35 × 10(-5) mol/L., Conclusion: Our findings suggest a new paradigm for cervical tissue morphology-one that includes the possibility of a specialized sphincter at the internal os. This new paradigm introduces novel avenues to further investigate potential mechanisms of normal and premature cervical remodeling., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Unlabelled: An appropriately timed cervical remodeling process is critical for a healthy delivery, yet little is known about the material property changes of the cervix in pregnancy because obtaining human tissue samples is difficult. Rodent models offer advantages including accurately timed pregnant tissues and genetically altered models. Determining the material properties of the mouse cervix, however, is challenging because of its small size and complex geometry. The aim of this study is to quantify cervical material property changes in a normal mouse pregnancy using a microstructurally-inspired porous fiber composite model. We mechanically test intact, whole, gestation-timed mouse cervix by pulling apart tensioned sutures through its inner canal. To interpret our mechanical testing results, we conduct an inverse finite element analysis, taking into account the combined loading state of the thick-walled cylindrical tissue. We fit the material model to previous osmotic swelling data and load-deformation data from this study using a nonlinear optimization scheme, and validate the model by predicting a separate set of deformation data. Overall, the proposed porous fiber composite model captures the mechanical behavior of the mouse cervix in large deformation. The evolution of cervical material parameters indicates that in a normal mouse pregnancy, the cervix begins to soften between day 6 and day 12 of a 19-day gestation period. The material parameter associated with the collagen fiber stiffness decreases from 3.4MPa at gestation day 6 to 9.7e-4MPa at gestation day 18, while the ground substance stiffness decreases from 2.6e-1MPa to 7.0e-4MPa., Statement of Significance: Accelerated cervical remodeling can lead to extremely premature births. Little is known, however, about the material property changes of the cervix in pregnancy because pregnant human tissue samples are limited. Rodent models overcome this limitation and provide access to gestation-timed samples. Measuring the material property changes of the mouse cervix in pregnancy is challenging due to its small size and complex geometry. Here, we establish a combined experimental and modeling framework. We use this framework to determine the cervical material property changes throughout a normal mouse pregnancy. We present our experimental methods for mechanically testing whole, intact cervical tissue samples. We fit a porous fiber composite material model to the mechanical data and show that the mouse cervix begins to soften between day 6 and day 12 of a 19-day gestation period., (Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Appropriate mechanical function of the uterine cervix is critical for maintaining a pregnancy to term so that the fetus can develop fully. At the end of pregnancy, however, the cervix must allow delivery, which requires it to markedly soften, shorten and dilate. There are multiple pathways to spontaneous preterm birth, the leading global cause of death in children less than 5 years old, but all culminate in premature cervical change, because that is the last step in the final common pathway to delivery. The mechanisms underlying premature cervical change in pregnancy are poorly understood, and therefore current clinical protocols to assess preterm birth risk are limited to surrogate markers of mechanical function, such as sonographically measured cervical length. This is what motivates us to study the cervix, for which we propose investigating clinical cervical function in parallel with a quantitative engineering evaluation of its structural function. We aspire to develop a common translational language, as well as generate a rigorous integrated clinical-engineering framework for assessing cervical mechanical function at the cellular to organ level. In this review, we embark on that challenge by describing the current landscape of clinical, biochemical, and engineering concepts associated with the mechanical function of the cervix during pregnancy. Our goal is to use this common platform to inspire novel approaches to delineate normal and abnormal cervical function in pregnancy., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The uterine cervix during pregnancy is the vital mechanical barrier which resists compressive and tensile loads generated from a growing fetus. Premature cervical remodeling and softening is hypothesized to result in the shortening of the cervix, which is known to increase a woman׳s risk of preterm birth. To understand the role of cervical material properties in preventing preterm birth, we derive a cervical material model based on previous mechanical, biochemical and histological experiments conducted on nonpregnant and pregnant human hysterectomy cervical tissue samples. In this study we present a three-dimensional fiber composite model that captures the equilibrium material behavior of the tissue in tension and compression. Cervical tissue is modeled as a fibrous composite material, where a single family of preferentially aligned and continuously distributed collagen fibers are embedded in a compressible neo-Hookean ground substance. The total stress in the collagen solid network is calculated by integrating the fiber stresses. The shape of the fiber distribution is described by an ellipsoid where semi-principal axis lengths are fit to optical coherence tomography measurements. The composite material model is fit to averaged mechanical testing data from uni-axial compression and tension experiments, and averaged material parameters are reported for nonpregnant and term pregnant human cervical tissue. The model is then evaluated by investigating the stress and strain state of a uniform thick-walled cylinder under a compressive stress with collagen fibers preferentially aligned in the circumferential direction. This material modeling framework for the equilibrium behavior of human cervical tissue serves as a basis to determine the role of preferentially-aligned cervical collagen fibers in preventing cervical deformation during pregnancy., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: The mechanical strength of the cervix relies on the cross-linking of the tissue's collagen network. Clinically, the internal os is functionally distinct from the external os. We sought to detect specific collagen cross-links in human cervical tissue and determine whether cross-link profiles were similar at the internal and external os., Study Design: Transverse slices of cervical tissue were obtained at the internal and external os from 13 nonpregnant, premenopausal women undergoing a benign hysterectomy. To understand how cross-links were distributed throughout the entire cervix and at the internal and external os, biopsies were obtained from 3 circumferential zones in 4 quadrants from each slice. Biopsies were pulverized, lyophilized, reduced with sodium borohydride, hydrolyzed with hydrochloric acid, and reconstituted in heptafluorobutyric acid buffer. Hydroxyproline was measured by ultraperformance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS), converted to total collagen, and normalized by dry weight. Collagen cross-links pyridinoline (PYD), deoxypyridinoline (DPD), dihydroxylysinonorleucine (DHLNL), and the nonenzymatic advanced glycation end product pentosidine (PEN) were measured by UPLC-ESI-MS/MS and reported as cross-link density ratio (cross-link/total collagen). Generalized estimated equation analysis was used to compare results between the internal and external os and to compare quadrants and zones within slices from the internal and external os to determine if cross-link profiles were similar., Results: A total of 592 samples from 13 patients were analyzed. Collagen cross-links are detectable in the human cervix by UPLC-ESI-MS/MS. When comparing all samples from the internal and external os, similar levels of collagen content, PYD, DHLNL, and DPD were found, but PEN density was higher at the external os (0.005 vs 0.004, P = .001). When comparing all internal os samples, significant heterogeneity was found in collagen content and cross-link densities across zones and quadrants. The external os exhibited heterogeneity only across zones., Conclusion: Collagen cross-links (PYD, DPD, DHLNL, and PEN) are detectable by UPLC-ESI-MS/MS in the human cervix. The internal os exhibits significant collagen cross-link heterogeneity compared with the external os. Further studies are needed to evaluate how collagen cross-link heterogeneity correlates to the mechanical strength and function of the human cervix., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The human cervix is an important mechanical barrier in pregnancy which must withstand the compressive and tensile forces generated from the growing fetus. Premature cervical shortening resulting from premature cervical remodeling and alterations of cervical material properties are known to increase a woman׳s risk of preterm birth (PTB). To understand the mechanical role of the cervix during pregnancy and to potentially develop indentation techniques for in vivo diagnostics to identify women who are at risk for premature cervical remodeling and thus preterm birth, we developed a spherical indentation technique to measure the time-dependent material properties of human cervical tissue taken from patients undergoing hysterectomy. In this study we present an inverse finite element analysis (IFEA) that optimizes material parameters of a viscoelastic material model to fit the stress-relaxation response of excised tissue slices to spherical indentation. Here we detail our IFEA methodology, report compressive viscoelastic material parameters for cervical tissue slices from nonpregnant (NP) and pregnant (PG) hysterectomy patients, and report slice-by-slice data for whole cervical tissue specimens. The material parameters reported here for human cervical tissue can be used to model the compressive time-dependent behavior of the tissue within a small strain regime of 25%., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Growth and remodeling of biological tissues involves mass exchanges between soluble building blocks in the tissue's interstitial fluid and the various constituents of cells and the extracellular matrix. As the content of these various constituents evolves with growth, associated material properties, such as the elastic modulus of the extracellular matrix, may similarly evolve. Therefore, growth theories may be formulated by accounting for the evolution of tissue composition over time in response to various biological and mechanical triggers. This approach has been the foundation of classical bone remodeling theories that successfully describe Wolff's law by establishing a dependence between Young's modulus and bone apparent density and by formulating a constitutive relation between bone mass supply and the state of strain. The goal of this study is to demonstrate that adding tissue composition as state variables in the constitutive relations governing the stress-strain response and the mass supply represents a very general and straightforward method to model interstitial growth and remodeling in a wide variety of biological tissues. The foundation for this approach is rooted in the framework of mixture theory, which models the tissue as a mixture of multiple solid and fluid constituents. A further generalization is to allow each solid constituent in a constrained solid mixture to have its own reference (stress-free) configuration. Several illustrations are provided, ranging from bone remodeling to cartilage tissue engineering and cervical remodeling during pregnancy., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Optical coherence tomography (OCT) is able to provide high resolution volumetric data for biological tissues. However, the field of view (FOV) of OCT is sometimes smaller than the field of interest, which limits the clinical application of OCT. One way to overcome the drawback is to stitch multiple 3D volumes. In this paper, we propose a novel method to register multiple overlapped volumetric OCT data into a single volume. The relative positions of overlapped volumes were estimated on en face plane and at depth. On en face plane, scale invariant feature transform (SIFT) was implemented to extract the keypoints in each volume. Based on the invariant features, volumes were paired through keypoint matching. Then, we formulated the relationship between paired offsets and absolute positions as a linear model and estimated the centroid of each volume using least square method. Moreover, we calibrated the depth displacement in each paired volume and aligned the z coordinates of volumes globally. The algorithm was validated through stitching multiple volumetric OCT datasets of human cervix tissue and of swine heart. The experimental results demonstrated that our method is capable of visualizing biological samples over a wider FOV, which enhances the investigation of tissue structure such as fiber orientation.

After a 3-step guided compliance procedure (vocal prompt, vocal plus model prompt, vocal prompt plus physical guidance) did not increase compliance, we evaluated 2 modifications with 4 preschool children who exhibited noncompliance. The first modification consisted of omission of the model prompt, and the second modification consisted of omitting the model prompt and decreasing the interprompt interval from 10 s to 5 s. Each of the modifications effectively increased compliance for 1 participant. For the remaining 2 participants, neither modification was effective; differential reinforcement in the form of contingent access to a preferred edible item was necessary to increase compliance. Problem behavior varied across participants, but was generally higher during guided compliance conditions and lower during differential reinforcement conditions.

The purpose of this research was to develop a reliable and repeatable inflation protocol to measure the scleral inflation response of mouse eyes to elevations in intraocular pressure (IOP), comparing the inflation response exhibited by the sclera of younger and older C57BL/6 mice. Whole, enucleated eyes from younger (2 month) and older (11 month) C57BL/6 mice were mounted by the cornea on a custom fixture and inflated according to a load-unload, ramp-hold pressurization regimen via a cannula connected to a saline-filled programmable syringe pump. First, the tissue was submitted to three load-unload cycles from 6 mmHg to 15 mmHg at a rate of 0.25 mmHg/s with ten minutes of recovery between cycles. Next the tissue was submitted to a series of ramp-hold tests to measure the creep behavior at different pressure levels. For each ramp-hold test, the tissue was loaded from 6 mmHg to the set pressure at a rate of 0.25 mmHg/s and held for 30 min, and then the specimens were unloaded to 6 mmHg for 10 min. This sequence was repeated for set pressures of: 10.5, 15, 22.5, 30, 37.5, and 45 mmHg. Scleral displacement was measured using digital image correlation (DIC), and fresh scleral thickness was measured optically for each specimen after testing. For comparison, scleral thickness was measured on untested fresh tissue and epoxy-fixed tissue from age-matched animals. Comparing the apex displacement of the different aged specimens, the sclera of older animals had a statistically significant stiffer response to pressurization than the sclera of younger animals. The stiffness of the pressure-displacement response of the apex measured in the small-strain (6-15 mmHg) and the large-strain (37.5-45 mmHg) regime, respectively, were 287 ± 100 mmHg/mm and 2381 ± 191 mmHg/mm for the older tissue and 193 ± 40 mmHg/mm and 1454 ± 93 mmHg/mm for the younger tissue (Student t-test, p<0.05). The scleral thickness varied regionally, being thickest in the peripapillary region and thinnest at the equator. Fresh scleral thickness did not differ significantly by age in this group of animals. This study presents a reliable inflation test protocol to measure the mechanical properties of mouse sclera. The inflation methodology was sensitive enough to measure scleral response to changes in IOP elevations between younger and older C57BL/6 mice. Further, the specimen-specific scleral displacement profile and thickness measurements will enable future development of specimen-specific finite element models to analyze the inflation data for material properties., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

An in vitro inflation test method was developed to characterize the mechanical behavior of the bovine posterior sclera. The method used digital image correlation to provide a spatially resolved, full-field deformation map of the surface of the posterior sclera in response to controlled pressurization. A series of experiments were performed in the range of 2-6 kPa (15-45 mmHg) to characterize the load-unload displacement response at various pressure rates and the time-dependent displacement response at different applied pressures. The magnitude of the displacement was largest in the peripapillary region, mainly between the apex and the optic nerve head. Further, the results showed that bovine scleral tissue exhibited nonlinear and viscoelastic behavior characterized by a rate-dependent displacement response, hysteresis during unloading and creep. The creep rate was insensitive to the applied pressure, suggesting that the tissue can be modeled as a quasilinear viscoelastic material in the physiological pressure range of 2-6 kPa., (Copyright © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

This study documents screening methods and services provided by health plan case managers for high need children in a Washington State health plan. Enrollees were screened to identify 315 children who had or were at risk of developing a chronic condition and were high users of health services. From this group, 46 children/families could be contacted and needed case management. Services included assessment of physical/social needs, patient education, referral to community resources, and benefit utilization. These services were different from care coordination provided in primary care practices.

This study documents care management services in 2 pediatric clinics for children with or at risk for a chronic condition during 8 months in 2005. Patients were identified by the clinic staff from a list provided by the health plan of patients at risk for or with a chronic condition. Care management services were documented for 161 of 189 selected patients. Services included family support, condition management, medical equipment management, and referrals to specialty care. Pediatric clinical care management activities directly relate to patient care and are complementary to, not duplicative of, case management provided by health plan managers.

Objective: The cervix is the lower portion of the uterus. It is composed of fibrous tissue and its mechanical integrity is crucial for maintaining a healthy gestation. During normal pregnancy, the cervical extracellular matrix (ECM) remodels in preparation for labor. The objective of this study was to investigate the biochemical and morphological changes in cervical stroma associated with physiological remodeling during normal pregnancy., Study Design: Using human cervical tissue obtained from pregnant and non-pregnant patients, the ECM was analyzed for its biochemical constituents and histologic morphology. The ECM was assayed for hydration, collagen concentration, collagen solubility, total sulfated glycosaminoglycan concentration, and individual disaccharide concentration. The ECM morphology was visualized using conventional histological techniques (Masson's trichrome stain, polarized light microscopy) as well as second harmonic generation (SHG) imaging., Results: When comparing pregnant to non-pregnant tissue, significant increases were measured for total sulfated glycosaminoglycans, hyaluronic acid, and collagen solubility. The microscopy studies confirmed that the collagenous network of the cervical stroma was anisotropic and pregnancy was associated with a discernable decrease in collagen organization., Conclusion: Significant changes were seen in the concentration and organization of cervical ECM constituents during normal pregnancy.

The process of selecting electronic health record systems is one of the most critical decisions in the journey towards automating and improving healthcare using information technology. However, there are a wide variety of problems associated with system selection and procurement processes in healthcare. Indeed the literature contains numerous examples of systems that were purchased and customized that failed to meet user needs, were implemented well behind schedule, which cost much more than expected and which in some cases failed completely. In this paper we describe a framework which we have developed and have begun to apply in considering key processes in the selection of electronic health records - i.e. the testing of potential candidate systems to determine if they meet user and institutional needs. The objective of our work is to improve our understanding of and the effectiveness of this critical decision making aspect of health informatics. In our work we consider system selection in terms of strength of evidence obtained from testing candidate systems.

The relationship between usability and training remains to be explored in health informatics. We examine the training given during the implementation of an institutional electronic medical record system, as well as the usability of the system from the perspective of new users who have been recently trained. We examine in which ways video-based usability testing with new users, who received classroom training one month earlier, can be used to a) indicate needed changes in the training program, and b) provide feedback to improve system customization and deployment. Usability testing methods were found to be an important adjunct to system deployment: they can improve the system implementation as well as suggest strategies for user education.

Acoustic trauma not only produces temporary and permanent hearing loss but is a common cause of chronic tinnitus. Recent work indicated a possible role for the transient receptor potential channel vanilloid subfamily type 1 (TRPV1) in modulating the effects of cochlear injury. In our research, we investigated the effects of acoustic damage on TRPV1 expression in spiral ganglion neurons of adult rats. After exposing them unilaterally to noise, we extracted cochleas and processed the spiral ganglion for TRPV1 expression at four posttrauma intervals (2 hours, 24 hours, 12 days, and 16.9 months). We measured TRPV1 immunodensity in the apical, middle, and basal turns of the cochlea. We found a significant interaction (p = .039) between posttrauma interval and regional cochlear receptor expression: For survival intervals between 24 hours and 2 weeks, TRPV1 density increased in all cochlear regions; at the longest survival interval (16.9 months), TRPV1 density was dramatically reduced in the basal region. We also psychophysically tested the long-survival subjects, which showed evidence of 20-kHz tonal tinnitus. These results suggest that TRPV1 may participate after cochlear injury in a signal cascade that is responsible for the neuroplastic events leading to tinnitus and hyperacusis.

The experience of Mount Sinai Hospital is representative of the challenges and problems facing large academic medical centers in selecting an ambulatory EMR. The facility successfully revived a stalled process in a challenging financial climate, using a framework of science and rigorous investigation. The process incorporated several innovations: 1) There was a thorough review of medical informatics literature to develop a mission statement, determine practical objectives and guide the demonstration process; 2) The process involved rigorous investigation of vendor statements, industry statements and other institution's views of vendors; 3) The initiative focused on user-centric selection, and the survey instrument was scientifically and specifically designed to assess user feedback; 4) There was scientific analysis of validated findings and survey results at all steering meetings; 5) The process included an assessment of vendors' ability to support research by identifying funded and published research; 6) Selection involved meticulous total cost of ownership analysis to assess and compare real costs of implementing a vendor solution; and finally, 7) There were iterative meetings with stakeholders, executives and users to understand needs, address concerns and communicate the vision.