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Laboratory evaluation of amalgam separators.

BACKGROUND: Amalgam in dental wastewater is receiving increasing scrutiny from regulators because of national, state and local initiatives to reduce or virtually eliminate the discharge of mercury and mercury-containing items into the environment. Amalgam separators are considered to be one means of reducing the amount of amalgam that dental offices discharge into sewers. The purpose of this study was to evaluate the amalgam removal efficiency of commercially available amalgam separators and the total mercury concentration in the effluent from laboratory testing. METHODS: The authors evaluated the amalgam removal efficiency of 12 amalgam separators according to International Organization for Standardization, or ISO, Standard 11143 for Amalgam Separators. Total mercury concentration in the effluent was calculated using the mass of amalgam particles larger than 1.2 micrometers and the volume of effluent, together with U.S. Environmental Protection Agency, or EPA, Method 245.1 for amalgam particles smaller than 1.2 microm. Total dissolved mercury also was determined. RESULTS: The results show that all 12 amalgam separators exceeded the ISO 11143 requirement of 95 percent amalgam removal efficiency. Statistical differences were found in the efficiencies of the separators. Both the total mercury concentration and total dissolved mercury concentration in the effluent demonstrated large variations. CONCLUSIONS AND CLINICAL IMPLICATIONS: This laboratory evaluation shows that amalgam separators removed at least 96.09 percent of the amalgam in samples with particle-size distribution as specified in ISO 11143. Total mercury concentration and total dissolved mercury concentration in the effluent varied widely for each amalgam separator. Additional research is needed to develop test methods to evaluate the efficiency of amalgam separators in removing small amalgam particles, colloidal amalgam particles and ionic mercury in solution.

Dental Amalgam↗

Objective biofidelity rating of a numerical human occupant model in frontal to lateral impact.

Both hardware crash dummies and mathematical human models have been developed largely using the same biomechanical data. For both, biofidelity is a main requirement. Since numerical modeling is not bound to hardware crash dummy design constraints, it allows more detailed modeling of the human and offering biofidelity for multiple directions. In this study the multi-directional biofidelity of the MADYMO human occupant model is assessed, to potentially protect occupants under various impact conditions. To evaluate the model's biofidelity, generally accepted requirements were used for frontal and lateral impact: tests proposed by EEVC and NHTSA and tests specified by ISO TR9790, respectively. A subset of the specified experiments was simulated with the human model. For lateral impact, the results were objectively rated according to the ISO protocol. Since no rating protocol was available for frontal impact, the ISO rating scheme for lateral was used for frontal, as far as possible. As a result, two scores show the overall model biofidelity for frontal and lateral impact, while individual ratings provide insight in the quality on body segment level. The results were compared with the results published for the THOR and WorldSID dummies, showing that the mathematical model exhibits a high level of multi-directional biofidelity. In addition, the performance of the human model in the NBDL 11G oblique test indicates a valid behavior of the model in intermediate directions as well. A new aspect of this study is the objective assessment of the multi-directional biofidelity of the mathematical human model according to accepted requirements. Although hardware dummies may always be used in regulations, it is expected that virtual testing with human models will serve in extrapolating outside the hardware test environment. This study was a first step towards simulating a wider range of impact conditions, such as angled impact and rollover.

Journal Article↗

Assessment of a computer-aided instructional program for the pediatric emergency department.

Computer aided instruction (CAI) software is becoming commonplace in medical education. Our experience with CAI programs in our pediatric ED raised concerns about the time commitment some of these programs require. We developed a just-in-time learning program, the Virtual Preceptor (VP) and evaluated this program for use in a busy clinical environment. Forty-three of 47 pediatric residents used the VP at least once. Interns used the program 2 (1/2) times more often than upper level residents. Of 321 topics available in 18 subject categories, 153 (48%) were selected at least once. Content was rated as appropriate by 72% of users. 95% of residents would use the program again. Although no resident felt the program itself took too long to use, 51% said they were too busy to use the VP. Time of use and level of training may be important factors in CAI use in the pediatric ED environment.

Analysis of Variance↗

A web-based workflow system for emergency healthcare.

Emergency healthcare delivery involves a variety of activities performed from the time of a call to the ambulance service till the time of patient's disposal from the emergency department of a hospital. Workflow systems have recently received considerable attention in the healthcare field since they overcome organizational structures and support collaboration and coordination requirements by automatically routing relevant information where and when needed. In particular, healthcare workflow systems implemented over the Web can form the basis for a collaborative environment by bringing together healthcare professionals who are geographically dispersed and, hence, creating virtual healthcare workgroups organized around patient care. In this paper, a web-based workflow system is presented that was developed to support emergency healthcare processes and to provide an infrastructure for the integration of pre-hospital and in-hospital emergency healthcare.

Emergency Service, Hospital↗

Development of a solid-phase assay for analysis of matrix metalloproteinase activity.

Proteases play fundamentally important roles in normal physiology and disease pathology. Methods for detection of active proteolysis may greatly aid in the diagnosis of disease progression, and suggest modes of therapeutic intervention. Most assays for proteolytic potential are limited by a lack of specificity and/or quantification. We have developed a solid-phase activity assay for members of the matrix metalloproteinase (MMP) family that is specific and can be used to quantify active enzyme concentration. The assay has two principal components: a capture antibody that immobilizes the MMP without perturbing the enzyme active site, and a fluorescence resonance energy transfer substrate for monitoring proteolysis at low enzyme concentrations. The assay was standardized for MMP-1, MMP-3, MMP-13, and MMP-14. The efficiency of the assay was found to be critically dependent upon the quality of the antibodies, the use of substrates exhibiting high specific activities for the enzymes, and enzyme samples that are fresh. The assay was applied to studies of constitutive and induced MMP activity in human melanoma cells. Analysis of several melanoma cell lines, and comparison with prior studies, correlated higher constitutive MMP-13 activity with higher levels of the cell surface receptor CD44. Ligands to two different melanoma cell surface receptors (the alpha2beta1 integrin or CD44) were found to induce different proteolytic profiles, suggesting that the extracellular matrix can modulate melanoma invasion. Overall, the solid-phase MMP activity assay was found to be valuable for analysis of protease activity in cellular environments. The solid-phase assay is suitably flexible to allow studies of virtually any proteolytic enzyme for which appropriate substrates and antibodies are available.

Amino Acid Sequence↗

Growth and differentiation of hyperplastic outgrowths derived from mouse mammary epithelial cells transformed in organ culture.

Potentially neoplastic outgrowths of BALB/c mouse mammary hyperplasia(s) (MH) derived from 7,12-dimethylbenz[a]anthracene-transformed epithelial cells in organ culture were characterized for responses to the hormones normally required for morphogenesis and functional differentiation of the mammary tissue. In a new culture model of the gland-free mammary fat pad, DNA synthesis in the MH outgrowths increased to a single peak during 6 days of incubation in a serum-free medium containing insulin, prolactin, aldosterone, and cortisol. The rise in DNA synthesis was accompanied by increased cell number and lobuloalveolar morphogenesis filling 50-70% of the fat pad; the rate of growth was variable among the MH outgrowth lines. Certain MH tissue showed some growth response in medium with aldosterone, cortisol, or estrogen, and progesterone in the presence of insulin. The hormone mixture insulin-prolactin was conducive to maximal growth, which suggested an altered sensitivity of the MH outgrowths to the mammogenic steroid hormones. Functional differentiation in the MH outgrowths was assessed in vivo by determination of the casein messenger RNA (mRNAcsn) levels measured by a specific complementary DNA probe. In MH-1 and MH-5 outgrowth lines, mRNAcsn was measurable in lactating hosts. In MH-9 outgrowth essentially the same concentration of mRNAcsn was present both in virgin and lactating hosts. Although mRNAcsn was present in MH outgrowths in lactating hosts, the concentration of the mRNA was only 0.056-0.88% of that present in the lactating host's own mammary gland. Virtually no mRNAcsn was measurable in the mammary tumors, regardless of the endocrine environment of the host animal. The results indicate a transformation-associated altered pattern of mammary cell-specific gene expression.

9,10-Dimethyl-1,2-benzanthracene↗

[Family environment risk factors of depression in adolescence].

General psychosocial theories of developmental psychopathology assert that family environment plays a significant role in forming both adaptive and maladaptive functioning of children. Also virtually all theories of depression assert that faulty parent-child relationships play a major role in the aetiology of this disorder. According these theoretical formulations familial risk factors have been the focus of most research on depression in adolescence. Several studies have shown that insecure attachment and parenting characterized by coldness, rejection, harsh discipline and unsupportive behaviour is positively related to adolescent depressive symptoms. Some research indicates that authoritative parenting, conceptualized as a composite of warmth, accept-involvement, firm control, and democratic discipline, is associated with the least depressive symptoms among adolescents. Pathogenetic factors within the family environment, such as parental depression, changes of family structure, violence or neglect, can also contribute to depression in adolescence. A causal relationship between anomalous parenting and depression is probably the interplay among genetic, cognitive, emotional, interpersonal and family environmental factors.

Adolescent↗

Depth-map-based scene analysis for active navigation in virtual angioscopy.

This paper presents a new approach dealing with virtual exploratory navigation inside vascular structures. It is based on the notion of active vision in which only visual perception drives the motion of the virtual angioscope. The proposed fly-through approach does not require a premodeling of the volume dataset or an interactive control of the virtual sensor during the fly-through. Active navigation combines the on-line computation of the scene view and its analysis, to automatically define the three-dimensional sensor path. The navigation environment and the camera-like model are first sketched. The basic stages of the active navigation framework are then described: the virtual image computation (based on ray casting), the scene analysis process (using depth map), the navigation strategy, and the virtual path estimation. Experimental results obtained from phantom model and patient computed tomography data are finally reported.

Algorithms↗

Neural underpinning of postural responses to visual field motion.

Numerous results emerging from current research strongly implicate the effect of Visual Field Motion on the organization of postural responses. However, this is the first empirical study exploring the neural substrates underlying the subjects' response to Visual Field Motion. Two separate experiments were conducted to investigate the subject responses to Visual Field Motion. In the first experiment, the standing subjects were exposed to Visual Field Motion in the VR environment. In the second experiment, the recumbent subjects viewed the same Visual Field Motion while in a MRI scanner. A virtual reality (VR) prototype of the moving room paradigm [Lee, D.N., Aronson, E., 1974. Visual proprioceptive control of standing in human infants. Perception & Psychophysics 15, 529-532] was developed to simulate various optic flow patterns in a controlled VR environment. Postural responses (center of pressure, body kinematics, vection, egomotion) and brain activation patterns (fMRI signals) were examined. The subjects experienced egomotion and have reported vection in both experiments only when certain attributes of Visual Field Motion were introduced. This was accompanied by significant activation of specific brain structures, including prefrontal, parietal cortices and bilateral cerebellum. We propose the existence of functional interactions between modality specific areas of the brain involved in postural responses to Visual Field Motion (VFM).

Adult↗

A volumetric approach to virtual simulation of functional endoscopic sinus surgery.

Advanced display technologies have made the virtual exploration of relatively complex models feasible in many applications. Unfortunately, only a few human interfaces allow natural interaction with the environment. Moreover, in surgical applications, such realistic interaction requires real-time rendering of volumetric data-placing an overwhelming performance burden on the system. We report on a collaboration of an interdisciplinary group developing a virtual reality system that provides intuitive interaction with volume data by employing real-time volume rendering and force feedback (haptic) sensations. We describe our rendering methods and the haptic devices and explain its utility of this system in the real-world application of Endoscopic Sinus Surgery (ESS) simulation.

Computer Simulation↗

The evolution of mass balance models of persistent organic pollutant fate in the environment.

Current approaches to modelling the fate of persistent organic pollutants (POPs) in the environment have evolved in response to four dominant characteristics of these substances; namely: (1) the presence of POPs in virtually all environmental phases and the ease with which they move from one to the other requires multi-compartmental modelling. Describing transport across phase boundaries becomes as, or even more, important as quantifying transport within the phases; (2) POPs may persist in the environment for many decades. For chemicals that 'have time', concepts such as equilibrium partitioning and steady-state become more important than for short-lived substances whose fate is more controlled by the rates of transformation; (3) measuring POPs is difficult and expensive and observed concentrations of POPs are not available in high spatial or temporal resolution. Consequently, high resolution tends not to be a high priority in POP models; and (4) detrimental effects of POPs often manifest themselves in top predators, which has led to a focus on modelling biotic uptake and transfer within food chains. The task of building a POPs model is viewed as combining the four 'building blocks' of partitioning, transport, transformation and source data with the help of the law of the conservation of mass. Process models, evaluative models, models of real local, regional and global fate, as well as biological uptake models are presented and references to numerous examples are provided. An attempt is made to forecast future directions in the field of POPs modelling. It is expected that modelling techniques that do not rely on quantitative emission estimates as well as approaches that take into account spatial, temporal and climatic variability as well as parameter uncertainty will increase in importance. Finally, the relationship between modelling POPs and models of other pollutant issues is addressed, as are potential interactions between POPs and pollutant issues such as eutrophication, acidification and global climate change.

Journal Article↗

Alleviating blood shortages in a resource-constrained environment.

BACKGROUND: The nation devotes considerable resources to the collection, processing, and distribution of blood products. Nonetheless, shortages of virtually every blood component persist. Economic theory suggests that the national blood supply can be increased either by increasing the level of resources used in the collection and production of blood components or by utilizing existing resources more efficiently. STUDY DESIGN AND METHODS: This study uses data envelopment analysis to analyze the efficiency of 70 blood centers to determine the extent to which operational efficiency can be improved, the increase in the nation's blood supply that would result, and management strategies that would lead to such improvements. Data were collected from the AABB 2002-2003 Directory of Community Blood Centers. RESULTS: The study found that roughly half of the 70 blood centers studied are efficient. The remaining blood centers collectively can both increase outputs and decrease some inputs. If the inefficient blood centers were to eliminate half of their inefficiency, then systemwide output of platelets would be increased by 17 percent, cryoprecipitate by 12 percent, plasma by 10 percent, and red blood cells by 7 percent. Inefficient blood centers have little opportunity to reduce full-time employees or reduce expenditures; however, they can decrease their use of part-time employees by 10 percent and volunteers by 9 percent. CONCLUSION: The results indicate that efficiency improvements would help to alleviate the nation's persistent blood shortages. These findings can be used by blood center managers to identify management interventions that can improve operational efficiency, resulting in greater output with existing levels of resources.

Blood Banks↗

Dissociable retrosplenial and hippocampal contributions to successful formation of survey representations.

During everyday navigation, humans encounter complex environments predominantly from a first-person perspective. Behavioral evidence suggests that these perceptual experiences can be used not only to acquire route knowledge but also to directly assemble map-like survey representations. Most studies of human navigation focus on the retrieval of previously learned environments, and the neural foundations of integrating sequential views into a coherent representation are not yet fully understood. We therefore used our recently introduced virtual-reality paradigm, which provides accuracy and reaction-time measurements precisely indicating the emergence of survey knowledge, and functional magnetic resonance imaging while participants repeatedly encoded a complex environment from a first-person ground-level perspective. Before the experiment, we gave specific instructions to induce survey learning, which, based on the clear evidence for emerging survey knowledge in the behavioral data from 11 participants, proved successful. Neuroimaging data revealed increasing activation across sessions only in bilateral retrosplenial cortices, thus paralleling behavioral measures of map expertise. In contrast, hippocampal activation did not follow absolute performance but rather reflected the amount of knowledge acquired in a given session. In other words, hippocampal activation was most prominent during the initial learning phase and decayed after performance had approached ceiling level. We therefore conclude that, during navigational learning, retrosplenial areas mainly serve to integrate egocentric spatial information with cues about self-motion, whereas the hippocampus is needed to incorporate new information into an emerging memory representation.

Adult↗

Meiotic aneuploidy in the XXY mouse: evidence that a compromised testicular environment increases the incidence of meiotic errors.

Male mammals with two X chromosomes are sterile due to the loss of virtually all germ cells in the differentiating testis. The survival of rare germ cells, however, can give rise to patches of normal-appearing spermatogenesis in the adult testis. Intracytoplasmic sperm injection (ICSI) makes possible the establishment of a pregnancy using spermatozoa from severely oligozoospermic men and, indeed, has been successful using spermatozoa from human 47,XXY (Klinefelter syndrome) males. The risk of an abnormal pregnancy, however, may be significantly increased since several studies have demonstrated elevated levels of aneuploidy in spermatozoa from Klinefelter syndrome men. This has been suggested to reflect the consequences of meiotic segregation in XXY germ cells; however, it is also possible that it is a consequence of abnormalities in meiotic regulation in the XXY testis. We have addressed this question experimentally in the XXY male mouse. Analysis of testicular spermatozoa from XXY and control males demonstrates a significant increase in meiotic aneuploidy in the XXY mouse. Since previous studies have demonstrated that germ cells in the adult XXY testis are exclusively XY, the meiotic abnormalities observed must be attributable to segregation errors in XY germ cells. These findings have potential significance for ICSI pregnancies using spermatozoa from other types of male factor infertility patients, since they raise the possibility that increased meiotic errors are a generalized feature of the severely oligozoospermic testis.

Aneuploidy↗

Training in cortical control of neuroprosthetic devices improves signal extraction from small neuronal ensembles.

We have recently developed a closed-loop environment in which we can test the ability of primates to control the motion of a virtual device using ensembles of simultaneously recorded neurons /29/. Here we use a maximum likelihood method to assess the information about task performance contained in the neuronal ensemble. We trained two animals to control the motion of a computer cursor in three dimensions. Initially the animals controlled cursor motion using arm movements, but eventually they learned to drive the cursor directly from cortical activity. Using a population vector (PV) based upon the relation between cortical activity and arm motion, the animals were able to control the cursor directly from the brain in a closed-loop environment, but with difficulty. We added a supervised learning method that modified the parameters of the PV according to task performance (adaptive PV), and found that animals were able to exert much finer control over the cursor motion from brain signals. Here we describe a maximum likelihood method (ML) to assess the information about target contained in neuronal ensemble activity. Using this method, we compared the information about target contained in the ensemble during arm control, during brain control early in the adaptive PV, and during brain control after the adaptive PV had settled and the animal could drive the cursor reliably and with fine gradations. During the arm-control task, the ML was able to determine the target of the movement in as few as 10% of the trials, and as many as 75% of the trials, with an average of 65%. This average dropped when the animals used a population vector to control motion of the cursor. On average we could determine the target in around 35% of the trials. This low percentage was also reflected in poor control of the cursor, so that the animal was unable to reach the target in a large percentage of trials. Supervised adjustment of the population vector parameters produced new weighting coefficients and directional tuning parameters for many neurons. This produced a much better performance of the brain-controlled cursor motion. It was also reflected in the maximum likelihood measure of cell activity, producing the correct target based only on neuronal activity in over 80% of the trials on average. The changes in maximum likelihood estimates of target location based on ensemble firing show that an animal's ability to regulate the motion of a cortically controlled device is not crucially dependent on the experimenter's ability to estimate intention from neuronal activity.

Action Potentials↗

Local skin hyperthermia due to transcutaneous electrode heat.

The hypothesis that a transcutaneous monitor electrode can heat skin beyond the electrode edge was tested. This heating would cause a skin thermistor probe, if placed too close to the transcutaneous electrode, to transduce an artifactually high skin temperature. In a skin servo control system, this might result in a cooler environment than desired. Eight premature newborns in humidified incubators were tested once each between one and five days of age. Mean skin temperatures at 0.5 cm, 1.5 cm, and 2.5 cm from the electrode edge were significantly higher after electrode placement, although there were virtually no temperature changes in two of the subjects. Transcutaneous monitor electrodes can heat the surrounding skin. This may affect environment temperature in a skin servo control system if the skin probe is placed too close to the transcutaneous electrode.

Blood Gas Monitoring, Transcutaneous↗

Simulated medical learning environments on the Internet.

Learning anatomy and surgical procedures requires both a conceptual understanding of three-dimensional anatomy and a hands-on manipulation of tools and tissue. Such virtual resources are not available widely, are expensive, and may be culturally disallowed. Simulation technology, using high-performance computers and graphics, permits realistic real-time display of anatomy. Haptics technology supports the ability to probe and feel this virtual anatomy through the use of virtual tools. The Internet permits world-wide access to resources. We have brought together high-performance servers and high-bandwidth communication using the Next Generation Internet and complex bimanual haptics to simulate a tool-based learning environment for wide use. This article presents the technologic basis of this environment and some evaluation of its use in the gross anatomy course at Stanford University.

Anatomy↗

Invasion as limitation to anti-angiogenic glioma therapy.

The inhibition of tumor angiogenesis could be an efficient therapeutic strategy for the treatment of malignant gliomas. Prominent neovascularization is induced by these tumors, and microvascular proliferation is a malignancy grading criterion. However, glioma cells can also invade the brain diffusely over long distances without necessarily requiring angiogenesis. Experimentally, it was shown that especially during early stages of growth in rodent brain, glioma cells can coopt the preexistent host vasculature to recruit their blood supply in the absence of neovascularization. This phenomenon was only observed in orthotopic models in which the tumor cells were implanted into the brain which is a densely vascularized environment, but not in subcutaneous models in which tumor cells are implanted into a virtual space. Using an orthotopic mouse model, we analyzed whether systemic anti-angiogenic therapy with an antibody against the vascular endothelial growth factor receptor-2 (VEGFR-2) could inhibit intracerebral growth of xenografted human glioblastoma cells and what effect this treatment had on tumor morphology and invasiveness. We found that anti-angiogenic therapy inhibited tumor growth by 80% compared to buffer-treated controls. The intratumoral microvessel density was reduced by at least 40% in treated animals compared to controls. However, in mice treated with the anti-VEGFR-2 antibody, we noticed a striking increase in the number and total area of small satellite tumors clustered around the primary mass. These satellites usually contained central vessel cores, and tumor cells often had migrated along blood vessels over long distances to eventually reach the surface and spread in the subarachnoid space. Systemic anti-angiogenic therapy can thus apparently increase the invasiveness of gliomas in the orthotopic model. Tumor cell invasion was tightly associated with preexistent blood vessels, suggesting that increased cooption of the host vasculature could represent a compensatory mechanism that is selected for by inhibiting adequate tumor vascularization.

Angiogenesis Inhibitors↗