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Multiaccommodative stimuli in VR systems: problems & solutions.

Virtual reality environments can introduce multiple and sometimes conflicting accommodative stimuli. For instance, with the high-powered lenses commonly used in head-mounted displays, small discrepancies in screen lens placement, caused by manufacturer error or user adjustment focus error, can change the focal depths of the image by a couple of diopters. This can introduce a binocular accommodative stimulus or, if the displacement between the two screens is unequal, an unequal (anisometropic) accommodative stimulus for the two eyes. Systems that allow simultaneous viewing of virtual and real images can also introduce a conflict in accommodative stimuli: When real and virtual images are at different focal planes, both cannot be in focus at the same time, though they may appear to be in similar locations in space. In this paper four unique designs are described that minimize the range of accommodative stimuli and maximize the visual system's ability to cope efficiently with the focus conflicts that remain: pinhole optics, monocular lens addition combined with aniso-accommodation, chromatic bifocal, and bifocal lens system. The advantages and disadvantages of each design are described and recommendation for design choice is given after consideration of the end use of the virtual reality system (e.g., low or high end, entertainment, technical, or medical use). The appropriate design modifications should allow greater user comfort and better performance.

Accommodation, Ocular↗

Introduction to the special issue on virtual reality environments in behavioral sciences.

Virtual reality (VR) is usually described in biology and in medicine as a collection of technologies that allow people to interact efficiently with three-dimensional (3-D) computerized databases in real time using their natural senses. This definition lacks any reference to head-mounted displays (HMDs) and instrumented clothing such as gloves or suits. In fact, less than 10% of VR healthcare applications in medicine are actually using any immersive equipment. However, if we focus our attention on behavioral sciences, where immersion is used by more than 50% of the applications, VR is described as an advanced form of human- computer interface that allows the user to interact with and become immersed in a computer-generated environment. This difference outlines a different vision of VR shared by psychologists, psychotherapists, and neuropsychologists: VR provides a new human-computer interaction paradigm in which users are no longer simply external observers of images on a computer screen but are active participants within a computer-generated 3-D virtual world. This special issue investigates this vision, presenting some of the most interesting applications actually developed in the area. Moreover, it discusses the clinical principles, human factors, and technological issues associated with the use of VR in the behavioral sciences.

Behavioral Sciences↗

High prevalence of unrecognized osteomalacia in hospital patients with rheumatoid arthritis.

A consecutive series of 31 patients with rheumatoid arthritis (RA) admitted over a 6-month period to the rheumatology unit of a District General Hospital were screened for possible osteomalacia. Transiliac bone biopsies were performed in 14 patients where the above diagnosis was suspected, yielding four (12.9%) cases of osteomalacia. All affected patients were elderly women who had a poor diet and were virtually housebound. Additional risk factors in two cases were partial gastrectomy and occult coeliac disease. Biochemical screening was of limited value in differential diagnosis, since elevated serum alkaline phosphatase levels were noted in both osteomalacic and non-osteomalacic patients. This study indicates that, in the West of Scotland at least, osteomalacia is a common, easily overlooked and treatable cause of morbidity in elderly patients with RA.

Adult↗

The effects of immersiveness on physiology.

The effects of varying levels of immersion in virtual reality environments on participant's heart rate, respiration rate, peripheral skin temperature, and skin resistance levels were examined. Subjective reports of presence were also noted. Participants were presented with a virtual environment of an airplane flight both as seen from a two-dimensional computer screen and as seen from within a head-mounted display. Subjects were randomly assigned to different order of conditions presented, but all subjects received both conditions. Differences between the non-phobics' physiological responses and the phobic's response when placed in a virtual environment related to the phobia were noted. Also noted were changes in physiology based on degree of immersion.

Adult↗

Adonis microcarpa (pheasant's eye) toxicity in pigs fed field pea screenings.

Seed of Adonis microcarpa (pheasant's eye) fed at 5.6 g/kg of the diet induced virtually total feed refusal within 3 d in growing and finishing pigs. It also caused vomiting, rapid and shallow breathing and death in a minority. These effects were probably caused by cardiac glycosides whose structure and effects closely resemble those of digoxin. Feed intake and growth recovered within 2 weeks of removal of the seed.

Animal Feed↗

Highlights of the evidence of benefit for women aged 40-49 years from the 14-year follow-up of the Breast Cancer Detection Demonstration Project.

Randomized breast cancer screening trials are helpful in establishing evidence of benefit when they yield statistically significant results. The results of individual randomized screening trials can vary greatly depending on the quality of the images, the frequency of screening, compliance, contamination, sample size, and the length and adequacy of follow-up. For women 40-49 years of age at entry the first randomized breast cancer screening trial, the Health Insurance Program of Greater New York (HIP), showed a statistically significant decrease of 24% in breast cancer mortality at 18 years of follow-up, virtually the same as the 23% decrease seen in women 50-59 years of age. At 10-12 years of follow-up, five of seven randomized trials have shown nonstatistical decreases in breast cancer mortality. No trials with fewer than 8 years of follow-up have shown a decrease in mortality for women 40-49 years of age; whereas seven trials have shown a decrease for women older than 50 years of age. The largest study on the screening of women aged 40-49 (93,471) was the Breast Cancer Detection Demonstration Program (BCDDP). This demonstration program was not a randomized trial but has yielded indirect supportive evidence for the screening of women aged 40-49, by comparing age group results. Three highlights of these studies are presented: (1) Mammography in the BCDDP (1970s) was improved greatly compared to that in the HIP study (1960s). Mammography detected 40% of the cancers in women 40-49 years of age in the HIP compared to 90% in the BCDDP. In women 50-59 years of age, mammography detected 60% of cancers in the HIP but 92% in the BCDDP. (2) Using annual two-view mammography plus clinical breast examination after the first screen of women 45 years of age and older, subsequent detection rates were virtually the same for all age groups. The number of women screened annually yields slightly more than two breast cancers per 1000 women, regardless of age group. (3) Similar types, sizes, stage distributions, and survival and case fatality rates were demonstrated in women aged 40-49, 50-59 and 60-69 years.

Adult↗

Newly identified invasion drivers define the tumor front in oral squamous cell carcinoma.

Cells at the invasive front of oral squamous cell carcinoma (OSCC) occupy a partial epithelial-to-mesenchymal transition (p-EMT) state that drives invasion and therapeutic resistance yet remains poorly understood. To define the regulators of this metastable state, we developed an isogenic OSCC model that captures stable epithelial and p-EMT phenotypes and used it to perform a genome-wide CRISPR invasion screen. This unbiased strategy identified 17 modulators of invasion, most previously unrecognized in cancer and virtually unexplored in OSCC, that converge on cytoskeletal remodeling, adhesion, and epigenetic regulation. Within this network, EDIL3 emerged as a central driver of EMT, invasion, and chemoresistance in head and neck cancer, extending prior reports in other tumor types. Importantly, the invasion signature derived from our screen localized with striking specificity to the tumor invasive front of human OSCC, providing direct clinical validation. Together, these findings reveal a novel, targetable network of transient invasion drivers defining the OSCC tumor front.

Journal Article↗

Use of the BRET 7TM receptor/beta-arrestin assay in drug discovery and screening.

To perform functional cell-based screening assays on seven-transmembrane (7TM) receptors, also known as G-protein coupled receptors, at least three distinct assays are currently needed to screen for G(alphas), G(alphai/0) or G(alphaq/11) signaling receptors. Therefore, there has long been a desire for a universal screening assay that could be used to screen all 7TM receptors independent of their signaling pathway. The receptor/beta-arrestin interaction is common to virtually all 7TM receptors. Therefore, an assay based on this interaction should achieve just that. Bioluminescence resonance energy transfer technology can be used to measure the receptor/beta-arrestin interaction in living cells but due to various technical and biological reasons, the use of the technology for compound screening has been limited. The recent development of beta-arrestin mutants that significantly improve the assay signal, in combination with new improved instrumentation, has transformed bioluminescence resonance energy transfer technology from being a highly specialized research tool in molecular pharmacology to a more drug screening-friendly technique that is useful in an industrial setting.

Arrestins↗

Computer-simulation technique for low dose computed tomographic screening.

OBJECTIVES: The purpose of this study is to assess the relative influence of noise and artifact in detecting lung nodules on low dose computed tomographic (CT) screening. METHODS: We develop the computer-simulation technique that allows tube current simulation and virtual nodule insertion in any CT images. The tube current simulation uses a reduction model that adds random Gaussian noise distribution to existing projection data. The virtual nodules are generated using a dedicated CT simulation tool with same scanner geometry. RESULTS: The coefficient of the correlations between the contrast-to-noise ratio of the actual scan and simulated tube current images was 0.98. There was no difference in CT number between virtual nodules and actual nodules [t test results = 0.60, t50(0.01) = 2.70 at 10 mA] and the coefficient of the correlations of the image noise was 0.99. CONCLUSIONS: Our technique is useful for systematic evaluation of radiation dose reduction and structure visibility in low-dose CT screening.

Computer Simulation↗

Detection of latent prostate cancer from routine screening: comparison with breast cancer screening.

OBJECTIVES: One criticism of routine prostate cancer screening is the possibility that latent prostate cancer would be detected and treated in men who would otherwise never need treatment for their prostate cancer. This increase in latent cancer detection with screening could lead to overtreatment, with its resulting increases in morbidity, mortality, and health care costs. In contrast, breast cancer screening is widely accepted, and there is little concern about latent breast cancer detection and overtreatment of breast cancer due to screening. This study compares the detection of latent prostate cancer from screening with the detection of latent cancer in an established cancer screening program (breast cancer screening) and examines the risk that screening leads to an increase in detection of latent cancer over traditional methods of detection for both breast and prostate cancer. METHODS: The present study reviews outcomes data from several large prostate and breast cancer screening trials. The natural history of latent prostate and breast cancer is then reviewed. By applying this information, the rate of latent prostate cancer detection and latent breast cancer detection with screening is compared. RESULTS: Recent large-scale prostate cancer screening studies have reported a latent cancer detection rate of 2.9% to 8.0%. This rate of detection is virtually the same as that found by traditional methods of detection. Ductal carcinoma in situ (DCIS) is a noninvasive breast cancer that accounts for 16.2% to 23.7% of breast cancers detected in screening programs using mammography. The literature estimates that DCIS will remain latent in 50% to 66% of patients. These data suggest that the latent breast cancer detection rate in screening programs is 8.1% to 15.6%, which is a threefold to fivefold increase compared with the detection rate of latent breast cancer prior to screening with mammography. CONCLUSIONS: These results suggest that the latent prostate cancer detection rate from screening is similar to or less than the latent breast cancer detection rate from screening. Furthermore, prostate cancer screening does not appear to increase the detection rate of latent cancer over traditional methods of detection. This should eliminate concern that prostate cancer screening will lead to overtreatment of prostate cancer.

Breast Neoplasms↗

3-D visualization of the newborn's hip joint using ultrasound and automatic image segmentation.

Graf's method has been established as a standardized procedure for the diagnostic screening of developmental dysplasia of the hip in newborns. In this procedure, a two dimensional ultrasound image that has to contain standardized landmarks is taken and evaluated interactively to calculate congruence indicators. Since these indicators are only derived from a 2-D scan, they do not reflect the spatial joint structure. In our study, we visualized three dimensional scans of newborns' hip joints that were obtained using a conventional ultrasound transducer and a commercial localizer system that was fixed to the scanhead. The landmarks were detected by automatic image segmentation to avoid examiner dependent findings. The landmark structures as well as an automatically determined virtual sphere approximating the femoral head were visualized color coded on a computer screen. This kind of visualization was found to be intuitive. The evaluation of the entire joint geometry and the 3-D relations between the acetabulum and the femoral head improves the reliability of the diagnostics.

Acetabulum↗

Canadian National Breast Screening Study-2: 13-year results of a randomized trial in women aged 50-59 years.

BACKGROUND: Screening for breast cancer with mammography in women aged 50 years or more has been shown to reduce mortality from breast cancer. However, the extent to which mammography contributes to the reduction of mortality in women who also undergo physical examination of the breasts is not known. This study was designed to compare breast cancer mortality following annual screening consisting of two-view mammography and physical examination of the breasts with mortality following annual screening by physical examination only. Breast self-examination was taught to all participants. METHODS: This trial randomly and individually assigned 39 405 women aged 50-59 years, recruited from January 1980 through March 1985, to one of the study arms. The women were followed by record linkage with the Canadian National Cancer Registry and National Mortality Database to December 31, 1993, and by active follow-up of breast cancer patients to June 30, 1996. RESULTS: Randomization achieved virtually equal distribution of demographic and breast cancer risk variables. At the first annual screen, 21% of the cancers found by mammography alone (in the mammography plus physical examination group) were 20 mm or more in size compared with 46% of those found by physical examination in the mammography plus physical examination group and 56% in the physical examination-only group. The corresponding percentages for screens 2-5 were 10%, 42%, and 50%, respectively. Screening detected 267 invasive breast cancers in the mammography plus physical examination group compared with 148 in the physical examination-only group. By December 31, 1993, 622 invasive and 71 in situ breast carcinomas were ascertained in the mammography plus physical examination group, and 610 and 16 were ascertained in the physical examination-only group. At 13-year follow-up, with 107 and 105 deaths from breast cancer in the respective groups, the cumulative rate ratio was 1.02 (95% confidence interval = 0.78-1.33). CONCLUSION: In women aged 50-59 years, the addition of annual mammography screening to physical examination has no impact on breast cancer mortality.

Breast Neoplasms↗

Virtual kinetics: using statistical experimental design for rapid analysis of enzyme inhibitor mechanisms.

Modern automated drug-screening can generate hundreds of inhibitor leads from diverse chemical sources in a short period of time. Traditional methods of inhibitor analysis are resource intensive and limit the number of inhibitors that can be analyzed for their mechanism of inhibition. This paper presents methods we have developed for rapid estimation of both potency and mechanism of potential inhibitor leads for a biochemically complex screening target (protein kinase C) using commercially available computer programs for statistical experimental design. Our findings indicate that, with careful choice of factor levels, statistical experimental design clearly identifies the various interactions of the assay components with inhibitors. Suitably plotted, the data can be used to examine the competitive nature of the inhibitor and can provide estimates of IC50 and Michaelis constants useful for planning further kinetic work. The techniques used are amenable to automation and should be useful for identifying inhibitors that may have only marginal potency, but exhibit desirable mechanistic profiles suitable for structural analoging efforts.

Antifungal Agents↗

Three-dimensional reconstruction of histological sections using modern product-design software.

BACKGROUND: Computer-based, three-dimensional reconstruction of histological sections is necessary for solving a diversity of questions in morphology and anatomy. Programming software for this purpose is difficult and time-consuming. Therefore, we tested if commercially available product-design software is useful for reconstructing anatomical virtual models. METHODS: We used Alias Wavefront Studio software on a Silicon Graphics workstation. Sections were projected with a newly developed microslide projector on a digitizing board and digitized interactively. Alternatively, pictures of sections were digitized on screen. The resulting set of contours was used as scaffold around which a surface was created manually. RESULTS: Repeated creation of the same object and subsequent measurements gave results that will be sufficiently reliable for many purposes. The visual presentation of objects satisfy highest demands. Little time is needed to reconstruct simple objects, and the time used for complex virtual models is acceptable. Manipulation of objects on screen is nearly in real time and rendering speed is high. CONCLUSIONS: Product-design software packages are a readily available and useful option for anatomists who want to do virtual reconstructions quickly without programming software themselves.

Animals↗

An antigen fragment encompassing the AD2 domains of glycoprotein B from two different strains is sufficient for differentiation of primary vs. recurrent human cytomegalovirus infection by ELISA.

Primary human cytomegalovirus (HCMV) infection during pregnancy is a frequent cause of fatal damage in populations with low prevalence of HCMV. Differentiation of primary vs. recurrent HCMV infection is an important issue in prenatal counseling. Antibodies specific for viral glycoproteins become detectable only with considerable delay with relation to HCMV infection or IgG seroconversion. Thus, lack of glycoprotein specific (gp-specific) antibodies can serve as a convenient indicator to identify those pregnant women that bear an elevated risk for HCMV transplacental transmission and fetal sequelae. In the opposite case, presence of gp-specific antibodies virtually excludes HCMV primary infection several weeks before sampling. However, no standardized screening assay for HCMV gp-specific antibodies had been available thus far. For this reason, an ELISA based on procaryotically expressed fragments of HCMV glycoprotein B (gB; gpUL55) was developed. Small fragments of gB from two different laboratory strains, encompassing the antigenic domain 2 (AD2) sufficed for sensitive and specific detection of gp-specific antibodies. The gB-ELISA titers correlated with titers of virus neutralizing antibodies in serum samples from primary or recurrent HCMV infections. Seroconversion kinetics of the gB-ELISA in samples from patients with primary HCMV infection closely paralleled the delay in seroconversion of gp-specific antibodies as determined by neutralization assay. Thus this assay provides a diagnostic tool that is easy to perform and can significantly add to available methods for the timely identification of primary HCMV infection during pregnancy. In addition, the gB-ELISA may be helpful in other clinical settings for the differentiation of primary HCMV infection from diseases caused by other pathogens.

Acute Disease↗

[MRI in gastrointestinal diseases].

Magnetic resonance imaging (MRI) has been called the most important development in medical diagnosis since the discovery of the X-ray more than 100 years ago. The effectiveness of MRI has been expanded to a variety of gastrointestinal disorders. The gastroenterologist's attention is currently focused on biliopancreatic and bowel diseases. Magnetic resonance cholangiopancreatography (MRCP) has become a competitive replacement for diagnostic endoscopic retrograde cholangiopancreatography (ERCP) in a variety of hepatobiliary and pancreatic diseases. MR enteroscopy has the potential to become the preferred method for evaluating the entire small bowel, while on the other hand virtual colonoscopy is far from being promoted as a tool for general screening purposes in suspected colon diseases. In summary, whether or not the survival of endoscopy is under debate, MRI could mark a historic turning point in gastroenterology. So, MRI hardware might interdisciplinarily be used by, e. g., radiologists and gastroenterologists.

Cholangiopancreatography, Endoscopic Retrograde↗

Navigation and image-guided HBP surgery: a review and preview.

Image-guided surgery and navigation have resulted from convergent developments in radiology, teletransmission, and computer science. Patient selection and preoperative planning in hepatobiliary-pancreatic (HBP) surgery rely on preoperative imaging. The operative procedure is finally led by the fusion of additional information gained by the palpating hand and intraoperative ultrasound. Despite advances in reducing morbidity and mortality, decisions are often hardly quantifiable and are restricted to super-specialists in HBP surgery. New developments in computed tomography (CT) and magnetic resonance imaging (MRI) technology have led to the possibility of the volumetric prediction of liver resections. These data can be shared via telemedicine and used for simulation and training. Three-dimensional (3D) reconstructions have led to a better topologic understanding of tumor-vascular tree relations in the individual patient. With the increasing use of ablative procedures and laparoscopy, intraoperative imaging and navigation will hold increasing significance for the HBP surgeon. Flat screen monitors adjacent to the surgical field present computer-generated 3D virtual liver resection proposals which can be transferred into the real liver. The main obstacles in HBP navigation are the flexibility and mobility of the target organ. Intrahepatic and surface markers seem to be mandatory for computer-navigated surgery. The first feasibility studies are promising.

Bile Ducts↗

The molecular cloning of the chromogranin A-like precursor of beta-granin and pancreastatin from the endocrine pancreas.

The cDNA encoding the precursor form of the chromogranin A-related proteins, beta-granin and pancreastatin, was obtained by immune screening of rat insulinoma and pancreatic islet cDNA libraries. The sequence was virtually identical to that of rat adrenal chromogranin A, suggesting that the different molecular forms of chromogranin A immunoreactivity found in adrenal medulla and endocrine pancreas are related to differences in post-translational proteolytic processing. The rat chromogranin A, unlike its bovine and human counterparts, contained a 20-residue glutamine sequence inserted within the N-terminal beta-granin sequence. Although the encoding CA(G/A) repeat recurs frequently in the rat genome, the rat chromogranin A molecule appears to be the product of a single gene and mRNA transcript.

Amino Acid Sequence↗