Diagnostic accuracy and cost-effectiveness of different strategies to triage women with adnexal masses: a prospective study.

OBJECTIVE: Transvaginal sonography (TVS) and serum biomarkers are used widely in clinical practice to triage women with adnexal masses, but the effectiveness of current biomarkers is weak. The aim of this study was to determine the best method of diagnosing patients with adnexal masses, in terms of diagnostic accuracy and economic costs, among four triage strategies: (1) the International Ovarian Tumor Analysis group's simple rules (SR) for interpretation of TVS with subjective assessment (SA) by an experienced ultrasound operator when TVS results are inconclusive (referred to hereafter as SR ± SA), (2) SR ± SA and cancer antigen 125 (CA 125), (3) SR ± SA and human epididymis protein 4 (HE4) and (4) SR ± SA and the risk of malignancy algorithm (ROMA). Our main hypothesis was that the addition of the biomarkers to SR ± SA could improve triaging of these patients in terms of diagnostic accuracy (i.e. malignant vs benign). As secondary analyses, we estimated the cost effectiveness of the four strategies and the diagnostic accuracy of SR ± SA at the study hospitals. METHODS: Between February 2013 and January 2015, 447 consecutive patients who were scheduled for surgery for an adnexal mass at the S. Anna and Mauriziano Hospitals in Turin were enrolled in this multicenter prospective cohort study. Preoperative TVS was performed and preoperative CA 125 and HE4 levels were measured. Pathology reports were used to assess the diagnostic accuracy of the four triage strategies and the cost of each strategy was calculated. RESULTS: A total of 391 patients were included in the analysis: 57% (n = 221) were premenopausal and 43% (n = 170) were postmenopausal. The overall prevalence of malignancy was 21%. SR were conclusive in 89% of patients and thus did not require SA; the overall performance of SR ± SA showed a sensitivity of 82%, specificity of 92% and positive and negative predictive values and positive and negative likelihood ratios of 74%, 95%, 10.5 and 0.19, respectively. In premenopausal women, mean cost among the four triage strategies varied from €36.41 for SR ± SA to €70.12 for SR ± SA + ROMA. The addition of biomarkers to SR ± SA showed no diagnostic advantage compared with SR ± SA alone and was more costly. Among postmenopausal women, mean cost among the four triage strategies varied from €39.52 for SR ± SA to €73.23 for SR ± SA + ROMA. Among these women, SR ± SA + CA 125 and SR ± SA + ROMA had a higher sensitivity (both 92% (95% CI, 85-99%)) than SR ± SA (81% (95% CI, 71-91%)), but SR ± SA had a higher specificity (84% (95% CI, 77-91%)). SR ± SA + CA 125 and SR ± SA + ROMA improved diagnostic accuracy, each diagnosing a third more malignant adnexal masses. In postmenopausal women, compared with SR ± SA alone, SR ± SA + CA 125 showed a net reclassification improvement (NRI) of 28.8% at an extra cost of €13.00, while the extra cost for SR ± SA + ROMA was €33.71, with a comparable gain, in terms of NRI, as that of SR ± SA + CA 125. CONCLUSIONS: In our study sample, SR ± SA seems to be the best strategy to triage women with adnexal masses for surgical management. Among postmenopausal women, SR ± SA + CA 125 increased the NRI at a reasonable extra cost. Our data do not justify the use of HE4 and ROMA in the initial triage of women with adnexal masses. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

A human model for road safety: from geometrical acquisition to model validation with radioss.

In order to investigate injury mechanisms, and to provide directions for road safety system improvements, the HUMOS project has lead to the development of a 3D finite element model of the human body in driving position. The model geometry was obtained from a 50th percentile adult male. It includes the description of all compact and trabecular bones, ligaments, tendons, skin, muscles and internal organs. Material properties were based on literature data and specific experiments performed for the project. The validation of the HUMOS model was first achieved on isolated segments and then on the whole model in both frontal and lateral impact situations. HUMOS responses were in good agreement with the experimental data used in the model validation and offers now a wide range of applications from crash simulation, optimization of safety systems, to biomedical and ergonomics.

The seated man: geometry acquisition and three-dimensional reconstruction.

A three-dimensional (3D) virtual human body in seated position can be used in a wide range of applications such as basic or clinical research. A male cadaver placed in the driving position in a car cockpit was frozen. Strictly parallel 5 mm thickness serial sections were then performed. Both sides of the slices were photographed, scanned and analyzed by anatomists with software tools, in order to produce accurate contours of the identified anatomical structures. A 3D reconstruction of organs, based on the marching cubes method, was achieved except for thin structures. This allowed an anatomical validation of these reconstructed elements. The result of this work is a complete geometrical database of a seated human body in the driving position including skin, all bones, internal organs and main muscle groups.

Memory sources associated with REM and NREM dream reports throughout the night: a new look at the data.

The data from three previously published studies on the memory sources of dreams, representing nine different moments of awakening throughout the night, are re-examined. In the original studies, elicited reports were recorded and segmented online into thematic units. The segmented reports were played back to Ss who were asked to identify memory sources or to associate to each segment. Memory sources were classified as episodic, semantic, or abstract self-references. In the meta-analysis and re-analyses reported here, the mean percentages of episodic memory sources are plotted separately for NREM and REM awakenings throughout the night. Within stages, neither NREM nor REM mean percentages differ significantly from each other, whereas between stages the mean percentage of episodic memory sources is significantly greater for NREM than for REM. Even when the correlation between report length and sleep stage is controlled by computing memory source density, the stage effect throughout the night persists for episodic memory sources. The relatively flat episodic memory curves for both NREM and REM indicate a rather constant recruitment of episodic memory sources throughout the night. No stage effect was found for strictly semantic memory sources. When semantic memory was defined generically, however, to include all non-spatio-temporal, "unmarked," information of self as well as of world, significantly more generic semantic memory sources derived from REM than from NREM reports, though not when corrected for the length of dream reports.

Lower Limb: Advanced FE Model and New Experimental Data.

The Lower Limb Model for Safety (LLMS) is a finite element model of the lower limb developed mainly for safety applications. It is based on a detailed description of the lower limb anatomy derived from CT and MRI scans collected on a subject close to a 50th percentile male. The main anatomical structures from ankle to hip (excluding the hip) were all modeled with deformable elements. The modeling of the foot and ankle region was based on a previous model Beillas et al. (1999) that has been modified. The global validation of the LLMS focused on the response of the isolated lower leg to axial loading, the response of the isolated knee to frontal and lateral impact, and the interaction of the whole model with a Hybrid III model in a sled environment, for a total of nine different set-ups. In order to better characterize the axial behavior of the lower leg, experiments conducted on cadaveric tibia and foot were reanalyzed and experimental corridors were proposed. Future work will include additional validation of the model using global data, joint kinematics data, and deformation data at the local level.

Amlodipine, a calcium channel inhibitor, and cocaine and ethanol's reinforcing effects.

The effects of amlodipine (from 0.1 to 3.0 mg/kg) on rats' pressing for rewarding brain stimulation, with and without cocaine administration, were assessed. None of the doses reliably modified the effects of cocaine. Also, amlodipine was given to two groups of rats taking alcohol: one group that was regularly taking a sweetened alcoholic beverage and the other taking an unsweetened alcoholic beverage. The only discernible effects of amlodipine on alcohol intake were associated with the highest dose and only with rats taking the sweetened beverage. The effects of this high dose could easily be attributable to behavioral toxicity elicited by the dose. In contrast, and confirming previous work, isradipine, another calcium channel inhibitor, produced reliable reductions on both cocaine's and alcohol's reinforcing effects. Despite the similarity of isradipine and amlodipine, isradipine apparently has some unique features with respect to cocaine and alcohol.

Symposium: Dream research methodology: The quest for dream sources.

Within a Human Information Processing (HIP) framework, dreaming can be subdivided into three main components: Input, Processing and Output. Until recently, only the Output has been extensively studied due to its relatively easy accessibility in the form of dream reports. Much less is known about the other two components. A method is presented by which one can get information on the nature of the input component to dream processing. In this method the subjects are requested to identify the memory sources of their dreams, collected upon experimental awakenings. The materials thus obtained are then classified into categories derived from Tulving's distinction between Episodic and Semantic memory. Several aspects, including interviewing and scoring procedures, had to be specified in order to use the method, which was applied in a series of studies. The aim was to clarify the similarities as well as the differences between REM and NREM dreams. The main results give further support to the hypothesis of the existence of a unique dream production system that operates at different levels of engagement during the various sleep phases.

Anatomy of the seated position: methodologic approach and initial findings.

The aim of this research was an anatomic study of the seated position in order to reply, in particular, to various questions raised in certain industrial situations as to this position and the reciprocal adaptation of the human being and his seat. The methodology adopted was based on obtaining reference serial sections from an entire subject frozen in the seated position, as well as on computerised three-dimensional reconstruction. The difficulty of the undertaking led us to specify this methodology, which must be strictly adhered to. Different types of visualisation were then considered, showing the feasibility of the method, which can effectively respond to the demands of industrial situations by allowing the creation of a data bank, and also by opening up new perspectives in the field of anatomical teaching.

Slow wave sleep dreaming.

Fifty volunteers slept two nonconsecutive nights in a sleep laboratory under electropolygraphic control. They were awakened for one report per night. Awakenings were made, in counterbalanced order, from slow wave sleep (SWS--stage 3-4 and stage 4) and rapid eye movement (REM) sleep. Following dream reporting, subjects were asked to identify memory sources of their dream imagery. Two independent judges reliably rated mentation reports for temporal units and for several content and structural dimensions. The same judges also categorized memory sources as autobiographical episodes, abstract self-references, or semantic knowledge. We found that REM reports were significantly longer than SWS reports. Minor content SWS-REM differences were also detected. Moreover, semantic knowledge was more frequently mentioned as a dream source for REM than for SWS dream reports. These findings are interpreted as supporting the hypothesis that dreaming is a continuous process that is not unique to REM sleep. Different levels of engagement of the cognitive system are responsible for the few SWS-REM differences that have been detected.

Cognitive aspects of mental activity during sleep.

Upon nighttime experimental awakening of 27 subjects in four sleep conditions (sleep onset early; sleep onset late; Stage 2; and rapid eye movement, REM, sleep), 108 dream reports and their association reports were collected. Dream reports were analyzed for length (temporal units) and content categories (continuity; implausibility; presence of the dreamer [i.e., "the self"], a setting, characters). Associations were classified as episodic, abstract self-referred, and semantic memories. The two sets of results tend to show a basic homogeneity among mentation reports in the four sleep conditions considered. These findings are interpreted as supporting the hypothesis that the same cognitive mechanisms operate, at different levels of engagement, in dream generation rather than the hypothesis of multiple dream-generation systems dependent upon the physiological characteristics of the various sleep stages.

Memory sources of REM and NREM dreams.

Sixteen male volunteers slept 4 nonconsecutive nights each in a sleep laboratory. They were awakened for one dream report per night. Awakenings were made, in counterbalanced order, from early-night and late-night rapid-eye movement (REM) and non-REM (NREM) sleep. Following dream reporting, subjects were asked to identify memory sources of their dream imagery. Two independent judges reliably rated mentation reports for temporal units and categorized memory sources as autobiographical episodes, abstract self-references, or semantic knowledge. We replicated earlier findings that semantic knowledge is more frequently mentioned as a dream source for REM than for NREM reports. However, with controls for length of reports, the REM-NREM difference disappeared, indicating that the stage difference in memory sources was not independent of stage difference in report lengths. There was a significant effect of time of night on source class, but only in REM sleep: Both without and with controls for report length, more semantic sources were cited for late than for early REM dreams.

Dream sources, associative mechanisms, and temporal dimension.

Using the technique of free association in an experimental setting, this author and colleagues previously found differences in the quality of memory traces involved in the production of REM and sleep onset (SO) dreams. The present study aims to answer two questions raised by those results: (a) Must the associative session be temporally contiguous to the dream production to gain access to the sources of the dream? (b) Are the differences between SO and REM associations due only to differences in structure and content of the two types of dream reports? Free associations with the same dream collected immediately after an experimental awakening were compared with those recalled 2 months later. A first group of results supports the hypothesis that free associations are sensitive to the proximity to the amount of dream production. A second group shows that the differences between SO and REM dreams noted in the previous research are not attributable to differences in formal characteristics of the report.

Differential access to memory traces in the production of mental experience.

Two experiments were performed to determine the nature of the memory traces used in the production of mental experiences (dreams, daydreams). Free associations with dreams, collected upon experimental awakenings in Sleep Onset and rapid eye movement (REM) sleep, were classified as strict episodes, abstract self-references, or semantic traces, adapting Tulving's model (Experiment 1). Results showed that associations with Sleep Onset dreams were mainly strict episodes while REM associations were evenly distributed: that represents a psychophysiological state-dependency of the access to memory traces. A comparison of free associations with dream, daydreams, and films (Experiment 2) showed a similarity between access to memory traces in daydreaming and Sleep Onset dreaming. Physiological condition was not a discriminating factor. This homogeneity suggests that cognitive processes involved in the creation of original narrative sequences may be similar in sleep and waking. These findings and their interpretation tend to support a unitary theory of the mind rather than dichotomous models which, in dream research, have often been misleading.

From classical to modern anatomy or computer-assisted biomechanics.

The authors describe their methodology - dissection, photography, informational - permitting a biomechanical approach together with the study of the changes in the topographic anatomy of a region during movement.

Self-representation in dream experiences during sleep onset and REM sleep.

The Scoring System for Latent Structure (SSLS) was used to test three hypotheses regarding the degree of self-participation in dreams reported during sleep onset (SO) and rapid eye movement (REM) sleep. These hypotheses were that (a) the ratio of interactive to associative sentences would be significantly greater in REM than in SO; (b) the level of Ego activity would be significantly greater in REM than in SO; and (c) the ratio between interactive sentences with Ego not present and interactive sentences with Ego present would be significantly different in REM and in SO. None of these hypotheses was confirmed. However, the following significant differences were found: (a) the ratio between sentences with Ego substituted and the total number of interactive sentences was greater in REM than in SO (p less than 0.05); (b) the ratio between sentences with Ego substituted and sentences with Ego present was greater (p less than 0.05) in REM than in SO; (c) the ratio between sentences with Ego inserted and sentences with Ego substituted was greater in SO than in REM (p less than 0.01); and (d) the relative incidence of defective Ego was greater (p less than 0.01) in SO than in REM. These data were interpreted in terms of psychodynamic models of dream formation.

Proliferation of arterial smooth muscle: glucocorticoid effect.

Tritiated thymidine radioautography was employed to study the effect of glucocorticoids on smooth muscle proliferation in rabbit arteries. In the aorta and pulmonary artery of rabbits with cholesterol atherolsclerosis, labelled cell counts showed that these steroids decrease the deoxyribonucleic acid synthesis in the intimal plaques. The inhibitory effect on thymidine uptake was found to be dose dependent and closely related to the antiinflammatory potency of the steroid tested. In another set of experiments the smooth muscle proliferation occurring in the rabbit carotid artery after disendothelization was studied. In these normolipemic animals the inhibition of DNA synthesis was particularly evident in the medial smooth muscle cell; concomitantly, in steroid-treated animals the myointimal thickening in the denuded area was less prominent. It is concluded that very likely the glucocorticoid effect on the artery is due to a direct interaction of the steroid with smooth muscle cells.

Smooth muscle cell response to endothelial injury.

Electron microscopy and autoradiography with 3H-thymidine have been employed to study the cellular dynamic of intimal thickening occurring in the rabbit carotid artery after selective endothelial injury. The results obtained suggest that migration of SMC of the tunica media rather than proliferation is the key event in the development of the intimal thickening.

Cell proliferation in the atherosclerotic plaques of cholesterol-fed rabbits. Part 3. Histological and radioautographic observations on glucocorticoids-treated rabbits.

Tritiated thymidine radioautography was employed to study the effect of cortisol and other glucocorticoids on cellular proliferation in the aorta and pulmonary artery of rabbits with cholesterol atherosclerosis. Labelled cell counts showed that glucocorticoids, even after one day and at a relatively low dose, decrease sharply the deoxyribonucleic acid synthesis in the intimal plaques. The hormonal influence on [3H]thymidine uptake seems to be a dose-dependent process. The relative potency of these steroids in inhibiting DNA synthesis in the plaques parallels closely their anti-inflammatory effectiveness. Conversely mineralocorticoids, including aldosterone and deoxycorticosterone, increase the rate of DNA synthesis in the plaques. It is concluded that the antiatherogenic effect of glucocorticoids on cholesterol-fed rabbits may be due, at least partly, to the inhibitory effect of these steroids on the DNA synthesis of the cellular components of the intimal plaques.