The effect of non-immersive virtual reality radiographic positioning simulation on first-year radiography students' image evaluation performance.

INTRODUCTION: Optimal radiographic image quality is critical because it affects the accuracy of the reporter's interpretation. Radiographers have an ethical obligation to obtain quality diagnostic images while protecting patients from unnecessary radiation, including minimizing rejected and repeated images. Repeated imaging due to positioning errors have increased in recent years. METHODS: This study evaluated the effectiveness of non-immersive virtual reality (VR) simulation on first-year students' evaluation of positioning errors on resultant knee and lumbar spine images. Crossover intervention design was used to deliver radiographic image evaluation instruction through traditional lecture and guided simulation using non-immersive VR to 33 first-year radiography students at a single academic institution located across four geographic program locations. Pre- and post-test knowledge assessments examined participants' ability to recognize positioning errors on multiple-choice and essay questions. RESULTS: Raw mean scores increased on multiple choice questions across the entire cohort for the knee (M = 0.82, SD = 3.38) and lumbar spine (M = 2.91, SD = 3.69) but there was no significant difference in performance by instructional method (p = 0.60). Essay questions reported very minimal to no raw mean score increases for the knee (M = 0.27, SD = 2.78) and lumbar spine (M = 0.00, SD = 2.55), with no significant difference in performance by instructional method (p = 0.72). CONCLUSION: Guided simulation instruction was shown to be as effective as traditional lecture. Results also suggest that novice learners better recognize image evaluation errors and corrections from a list of options but have not yet achieved the level of competence needed to independently evaluate radiographic images for diagnostic criteria. IMPLICATIONS FOR PRACTICE: Non-immersive VR simulation is an effective tool for image evaluation instruction. VR increases access to authentic image evaluation practice by providing a simulated resultant image based off the students' applied positioning skills.

MLK3 is critical for breast cancer cell migration and promotes a malignant phenotype in mammary epithelial cells.

The malignant phenotype in breast cancer is driven by aberrant signal transduction pathways. Mixed-lineage kinase-3 (MLK3) is a mammalian mitogen-activated protein kinase kinase kinase (MAP3K) that activates multiple MAPK pathways. Depending on the cellular context, MLK3 has been implicated in apoptosis, proliferation, migration and differentiation. Here we investigated the effect of MLK3 and its signaling to MAPKs in the acquisition of malignancy in breast cancer. We show that MLK3 is highly expressed in breast cancer cells. We provide evidence that MLK3's catalytic activity and signaling to c-jun N-terminal kinase (JNK) is required for migration of highly invasive breast cancer cells and for MLK3-induced migration of mammary epithelial cells. Expression of active MLK3 is sufficient to induce the invasion of mammary epithelial cells, which requires AP-1 activity and is accompanied by the expression of several proteins corresponding to AP-1-regulated invasion genes. To assess MLK3's contribution to the breast cancer malignant phenotype in a more physiological setting, we implemented a strategy to inducibly express active MLK3 in the preformed acini of MCF10A cells grown in 3D Matrigel. Induction of MLK3 expression dramatically increases acinar size and modestly perturbs apicobasal polarity. Remarkably, MLK3 expression induces luminal repopulation and suppresses the expression of the pro-apoptotic protein BimEL, as has been observed in Her2/Neu-expressing acini. Taken together, our data show that MLK3-JNK-AP-1 signaling is critical for breast cancer cell migration and invasion. Our current study uncovers both a proliferative and novel antiapoptotic role for MLK3 in the acquisition of a malignant phenotype in mammary epithelial cells. Thus, MLK3 may be an important therapeutic target for the treatment of invasive breast cancer.

Homosexuality, birth order, and evolution: toward an equilibrium reproductive economics of homosexuality.

The survival of a human predisposition for homosexuality can be explained by sexual orientation being a polygenetic trait that is influenced by a number of genes. During development these shift male brain development in the female direction. Inheritance of several such alleles produces homosexuality. Single alleles make for greater sensitivity, empathy, tendermindedness, and kindness. These traits make heterosexual carriers of the genes better fathers and more attractive mates. There is a balanced polymorphism in which the feminizing effect of these alleles in heterosexuals offsets the adverse effects (on reproductive success) of these alleles' contribution to homosexuality. A similar effect probably occurs for genes that can produce lesbianism in females. The whole system survives because it serves to provide a high degree of variability among the personalities of offspring, providing the genotype with diversification and reducing competition among offspring for the same niches. An allele with a large effect can survive in these circumstances in males, but it is less likely to survive in females. The birth order effect on homosexuality is probably a by-product of a biological mechanism that shifts personalities more in the feminine direction in the later born sons, reducing the probability of these sons engaging in unproductive competition with each other.

Role of faulty visual search in the satisfaction of search effect in chest radiography.

RATIONALE AND OBJECTIVES: The authors tested the hypothesis that satisfaction of search effect, which is associated with the failure to detect native chest abnormalities in the presence of simulated nodules, is caused by reduced gaze on the native abnormalities. MATERIALS AND METHODS: Gaze dwell time of 20 radiologists was recorded for the region around abnormalities on images. Ten radiographs were reviewed, nine of which contained native abnormalities. Each image was seen with and without a simulated nodule. RESULTS: The decrease in the rate of true-positive findings in the detection of native abnormalities on images that contained simulated nodules confirmed the occurrence of a satisfaction of search effect. Gaze times on native abnormalities (up to the time of report of the abnormalities) were the same for images with nodules in which native abnormalities were missed (gaze time, 9.4 seconds) as they were for images without nodules in which native abnormalities were detected (gaze time, 9.5 seconds). Gaze time on missed native abnormalities was not affected by the presence (7.80 seconds) or absence (7.45 seconds) of nodules. CONCLUSION: Reduction in gaze dwell time on the missed abnormalities is not the cause of satisfaction of search errors in chest radiographs.

Mismatch repair by efficient nick-directed, and less efficient mismatch-specific, mechanisms in homologous recombination intermediates in Chinese hamster ovary cells.

Repair of single-base mismatches formed in recombination intermediates in vivo was investigated in Chinese hamster ovary cells. Extrachromosomal recombination was stimulated by double-strand breaks (DSBs) introduced into regions of shared homology in pairs of plasmid substrates heteroallelic at 11 phenotypically silent mutations. Recombination was expected to occur primarily by single-strand annealing, yielding predicted heteroduplex DNA (hDNA) regions with three to nine mismatches. Product spectra were consistent with hDNA only occurring between DSBs. Nicks were predicted on opposite strands flanking hDNA at positions corresponding to original DSB sites. Most products had continuous marker patterns, and observed conversion gradients closely matched predicted gradients for repair initiated at nicks, consistent with an efficient nick-directed, excision-based mismatch repair system. Discontinuous patterns, seen in approximately 10% of products, and deviations from predicted gradients provided evidence for less efficient mismatch-specific repair, including G-A-->G-C specific repair that may reflect processing by a homologue of Escherichia coli MutY. Mismatch repair was > 80% efficient, which is higher than seen previously with covalently closed, artificial hDNA substrates. Products were found in which all mismatches were repaired in a single tract initiated from one or the other nick. We also observed products resulting from two tracts of intermediate length initiated from two nicks.

Cause of satisfaction of search effects in contrast studies of the abdomen.

RATIONALE AND OBJECTIVES: Extraintestinal abnormalities visible without contrast material on abdominal radiographs are reported less frequently when contrast examinations are performed. Gaze dwell time was used to determine whether this difference is due to failure by observers to scan plain-film regions of contrast studies or discounting of plain-film abnormalities that were actually scanned. METHODS: Patients were included whose contrast studies had elicited the largest reductions in positive responses compared with their plain-film studies in a previous detection experiment. Gaze of 10 radiologists was studied. RESULTS: Significantly less time was spent gazing at non-contrast regions of contrast examinations than at the corresponding regions of radiographs. Errors with radiographs were based primarily on failures of recognition and decision making, whereas errors with contrast studies were based primarily on faulty scanning. CONCLUSION: Satisfaction of search errors on contrast examinations are caused by reduction in scanning of noncontrast regions.

Design and development of an electromechanical ultrasound probe holder for urodynamics testing.

A prevalent difficulty in urodynamics studies employing ultrasonography is associated with the manual application of the imaging transducer to the perineum. We have developed an electromechanically operated device for remote positioning of an ultra-sound probe during voiding studies of the lower urinary tract. The mechanical arm holds the probe inside a funnel that is mounted underneath a modified portable commode on which the patient is seated. External manually operated mechanical slides are used to translate the probe along the three primary axes for initial lateral and vertical positioning. Backwards/forwards and left/right pivoting of the transducer is then accomplished via linear stepper motors that are operated with a hand-held controller. A preliminary evaluation has shown that the device is easy to use, safe, and allows excellent visualization of the bladder outlet and proximal urethra in both male and female patients. The capability to remotely adjust the imaging angle allows the patient to void in a more private setting behind a drawn curtain, thereby minimizing the psychological distress associated with this test and facilitating the acquisition of more physiological test results.

Reported myopia in opposite sex twins: a hormonal hypothesis.

Two studies have reported poor vision in opposite sex twins (evidenced by wearing glasses or low visual acuity, both of which are interpreted here as evidence of myopia), whereas none have reported an absence of such effects. If these reports are replicable, it would suggest a hormonal effect. There is one report of higher testosterone levels in those suffering from high myopia. A possible mechanism would be if sex hormones in opposite sex pairs transfer from one fetus to the other. There is evidence that sex hormones can cross the placenta, and reports of sex differences in the development of opposite sex twins are consistent with such transfers. If different parts of the eye respond differentially to sex hormones, eyes developing in the unusual hormonal environment of opposite sex twins would be expected to have high myopia rates.

X-ray structure of a DNA decamer containing 7,8-dihydro-8-oxoguanine.

We have determined the x-ray structure of a DNA fragment containing 7,8-dihydro-8-oxoguanine (G(O)). The structure of the duplex form of d(CCAGOCGCTGG) has been determined to 1.6-A resolution. The results demonstrate that GO forms Watson-Crick base pairs with the opposite C and that G(O) is in the anti conformation. Structural perturbations induced by C.G(O)anti base pairs are subtle. The structure allows us to identify probable elements by which the DNA repair protein MutM recognizes its substrates. Hydrogen bond donors/acceptors within the major groove are the most likely element. In that groove, the pattern of hydrogen-bond donors/acceptors of C.G(O)anti is unique. Additional structural analysis indicates that conversion of G to G(O) would not significantly influence the glycosidic torsion preference of the nucleoside. There is no steric interaction of the 8-oxygen of G(O) with the phospho-deoxyribose backbone.

Analysis of the effect of hormones on opposite-sex twin attitudes.

Numerous reports in the literature suggest that hormones may transfer from one fetus to another, in humans as in animals. In a large sample of over seven thousand Australian adult twins, it was found that opposite-sex females showed a statistically significant tendency to hold more masculine attitudes than did same-sex female twins. This may be due to post-natal social interaction, but could also be caused by the transfer of testosterone from the male to the female fetus in opposite-sex twins.

The role of cell cycle redistribution in radiosensitization: implications regarding the mechanism of fluorodeoxyuridine radiosensitization.

PURPOSE: Radiosensitization has previously been demonstrated in a human colon cancer cell line (HT-29) following a 2 h exposure to low, clinically relevant concentrations (0.05-0.5 microM) of fluorodeoxyuridine (FdUrd) (15). The sensitizer enhancement ratio value (measured at 10% survival) plateaued at approximately 1.7 between 16 and 32 h following removal of drug. Parallel studies investigating the effect of FdUrd on the distribution of cells throughout the cell cycle found that the percentage of cells in early S-phase increased to approximately 70% during the same period that maximal radiosensitization was noted. As a follow-up to these findings, experiments have been designed to investigate the contribution of this early S-phase delay to radiosensitization. METHODS AND MATERIALS: Synchronized populations of HT-29 cells have been obtained with three separate techniques. Two involve the induction of a reversible metaphase arrest (with high pressure N2O or colcemid) followed by a shakeoff of mitotic cells. The third uses a plant amino acid, mimosine, to induce a reversible block at the G1/S boundary. Flow cytometry was used to analyze the degree of synchrony based on bromodeoxyuridine (BrdUrd) uptake and propidium iodide (PI) staining. Radiation survival curves were obtained on these synchronized populations to investigate changes in radiosensitivity through the cell cycle. Additionally, levels of thymidylate synthase (TS), the primary target of FdUrd cytotoxicity, were measured in each phase of the cell cycle using the TS 106 monoclonal antibody against human TS. RESULTS: Synchronization with mitotic shakeoff produced relatively pure populations of cells in G1; however, the degree of synchrony in early S-phase was limited both by cells remaining in G1 and by cells progressing into late S-phase. These techniques failed to reveal increased radiosensitivity in early S-phase at 10% survival. An 18 h exposure to mimosine resulted in populations that more closely resembled the early S-phase enrichment following FdUrd exposure and revealed increased radiosensitivity during early S-phase. TS levels were noted to be only 1.3 times higher in S phase than in G0/G1. CONCLUSION: Radiation survival data from cells synchronized with mitotic shakeoff techniques suggest that early S-phase delay is unlikely to be the primary mechanism of FdUrd radiosensitization. In contrast, the increased sensitivity seen in early S-phase with mimosine synchronized cells is similar to that seen with FdUrd. Although confounding biochemical pertubations cannot be ruled out, these data continue to suggest an association between early S-phase enrichment and radiosensitization. The significance of TS inhibition as a mechanism of FdUrd radiosensitization remains unclear.

4-Hydroxytamoxifen, an active metabolite of tamoxifen, does not alter the radiation sensitivity of MCF-7 breast carcinoma cells irradiated in vitro.

The effect of 4-hydroxytamoxifen (4OH-TAM), the potent anti-estrogenic metabolite of tamoxifen, on the radiosensitivity of MCF-7 cells irradiated in vitro was determined. Radiation dose response curves were generated for MCF-7 cells maintained and irradiated in phenol red-free medium containing 10(-10) M estradiol (E2) with or without 10(-7) M 4OH-TAM. Immediately after irradiation cells were transferred to medium containing 10(-10) ME2 supplemented with bovine serum to stimulate colony formation. Estradiol-stimulated cell proliferation was inhibited by 10(-7) M 4OH-TAM, but radiation sensitivity was not significantly altered (p > 0.3). Continued incubation in the absence of E2 for an additional 24 hours after irradiation likewise failed to alter the radiosensitivity of 4OH-TAM-treated MCF-7 cells. These studies indicate that growth-inhibitory concentrations of the anti-estrogen 4OH-TAM do not modify the in vitro radiation sensitivity of this line of human breast carcinoma cells.

Deoxyribonucleoside triphosphate pools and thymidine chemosensitization in human T-cell leukemia.

Thymidine kills cells by depleting dCTP stores. The present experiments tested whether deoxycytidine, by replenishing dCTP pools, could prevent thymidine cytotoxicity and thymidine's enhancement of carboplatin killing in two human T-cell acute leukemia cell lines. MOLT3 and JM cells were exposed to combinations of thymidine, deoxycytidine, and carboplatin and then assessed for survival, the magnitude of thymidine-carboplatin chemosensitization, and changes in deoxyribonucleoside triphosphate pools. For both cell lines, deoxycytidine (up to 144.5 micrograms/ml x 24 h) completely restored dCTP pools but only partially protected against thymidine cytotoxicity (100-1000 micrograms/ml x 24 h) and thymidine-carboplatin sensitization (up to 60 micrograms carboplatin/ml during the last hour of thymidine). This contrasts with complete protection in prior studies using other cell types. Thymidine alone markedly increased dTTP and dGTP pools and decreased dCTP; dATP pools underwent a sharp decline which has not been observed before in any cell line. In subsequent studies 0.0336-137.3 micrograms deoxyadenosine/ml partially prevented cytotoxicity and carboplatin sensitization by 300 micrograms thymidine/ml. Together, deoxycytidine and deoxyadenosine completely prevented thymidine-carboplatin sensitization even though dATP and dCTP pools were not entirely returned to normal. These findings are discussed in regard to the unusual sensitivity of T-cell malignancies to thymidine toxicity, mechanisms of cytotoxicity and chemosensitization by thymidine, and the possibility of thymidine selectively sensitizing T-cell malignancies to killing by alkylating agents.