Importance of magnetic information for neuronal plasticity in desert ants.

Many animal species rely on the Earth's magnetic field during navigation, but where in the brain magnetic information is processed is still unknown. To unravel this, we manipulated the natural magnetic field at the nest entrance of Cataglyphis desert ants and investigated how this affects relevant brain regions during early compass calibration. We found that manipulating the Earth's magnetic field has profound effects on neuronal plasticity in two sensory integration centers. Magnetic field manipulations interfere with a typical look-back behavior during learning walks of naive ants. Most importantly, structural analyses in the ants' neuronal compass (central complex) and memory centers (mushroom bodies) demonstrate that magnetic information affects neuronal plasticity during early visual learning. This suggests that magnetic information does not only serve as a compass cue for navigation but also as a global reference system crucial for spatial memory formation. We propose a neural circuit for integration of magnetic information into visual guidance networks in the ant brain. Taken together, our results provide an insight into the neural substrate for magnetic navigation in insects.

Imaging in gynecological disease (27): clinical and ultrasound characteristics of recurrent ovarian stromal cell tumors.

OBJECTIVE: To describe the clinical and ultrasound characteristics of recurrent granulosa cell and Sertoli-Leydig cell tumors. METHODS: This was a retrospective observational study performed at Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricovero e Cura a Carattere Scientifico, IRCCS, Rome (Gemelli center), Italy. Patients with a histological diagnosis of recurrent granulosa cell tumor or Sertoli-Leydig cell tumor were identified from the database of the Department of Gynecological Oncology. Those who had undergone a preoperative ultrasound examination at the Gemelli center between 2012 and 2020 were included, and the data retrieved from the original ultrasound reports. In all of these reports, the recurrent tumors were described using International Ovarian Tumor Analysis (IOTA) terminology. If a patient had more than one episode of relapse, information from all episodes was collected. If there was more than one recurrent tumor at the same ultrasound examination, all tumors were included. One expert sonographer also reviewed all available ultrasound images to identify typical ultrasound patterns using pattern recognition. RESULTS: We identified 30 patients with a histological diagnosis of recurrent granulosa cell tumor (25 patients, 55 tumors) or Sertoli-Leydig cell tumor (five patients, seven tumors). All 30 had undergone at least one preoperative ultrasound examination at the Gemelli center and were included. These women had a total of 66 episodes of relapse, of which a preoperative ultrasound examination had been performed at the Gemelli center in 34, revealing 62 recurrent lesions: one in 22/34 (64.7%) episodes of relapse, two in 4/34 (11.8%) episodes and three or more in 8/34 (23.5%) episodes. Most recurrent granulosa cell tumors (38/55, 69.1%) and recurrent Sertoli-Leydig tumors (6/7, 85.7%) were classified as solid or multilocular-solid tumors, while 8/55 (14.5%) recurrent granulosa cell tumors and 1/7 (14.3%) recurrent Sertoli-Leydig cell tumors were unilocular cysts and 9/55 (16.4%) recurrent granulosa cell tumors were multilocular cysts. The nine unilocular cysts had contents that were anechoic (n = 2) or had low-level echogenicity (n = 7), had either smooth (n = 4) or irregular (n = 5) internal cyst walls, and ranged in largest diameter from 8 to 38 mm, with three being < 20 mm and five being 20-30 mm. On retrospective review of the images, two typical ultrasound patterns were described: small solid tumor measuring < 2 cm (15/62, 24.2%) and tumor with vascularized echogenic ground-glass-like content (12/62, 19.4%). CONCLUSIONS: Some granulosa cell and Sertoli-Leydig cell recurrences manifest one of two typical ultrasound patterns, while some appear as unilocular cysts. These are usually classified as benign, but in patients being followed up for a granulosa cell tumor or Sertoli-Leydig cell tumor, a unilocular cyst should be considered suspicious of recurrence. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Estimating risk of endometrial malignancy and other intracavitary uterine pathology in women without abnormal uterine bleeding using IETA-1 multinomial regression model: validation study.

OBJECTIVES: To assess the ability of the International Endometrial Tumor Analysis (IETA)-1 polynomial regression model to estimate the risk of endometrial cancer (EC) and other intracavitary uterine pathology in women without abnormal uterine bleeding. METHODS: This was a retrospective study, in which we validated the IETA-1 model on the IETA-3 study cohort (n = 1745). The IETA-3 study is a prospective observational multicenter study. It includes women without vaginal bleeding who underwent a standardized transvaginal ultrasound examination in one of seven ultrasound centers between January 2011 and December 2018. The ultrasonography was performed either as part of a routine gynecological examination, during follow-up of non-endometrial pathology, in the work-up before fertility treatment or before treatment for uterine prolapse or ovarian pathology. Ultrasonographic findings were described using IETA terminology and were compared with histology, or with results of clinical and ultrasound follow-up of at least 1 year if endometrial sampling was not performed. The IETA-1 model, which was created using data from patients with abnormal uterine bleeding, predicts four histological outcomes: (1) EC or endometrial intraepithelial neoplasia (EIN); (2) endometrial polyp or intracavitary myoma; (3) proliferative or secretory endometrium, endometritis, or endometrial hyperplasia without atypia; and (4) endometrial atrophy. The predictors in the model are age, body mass index and seven ultrasound variables (visibility of the endometrium, endometrial thickness, color score, cysts in the endometrium, non-uniform echogenicity of the endometrium, presence of a bright edge, presence of a single dominant vessel). We analyzed the discriminative ability of the model (area under the receiver-operating-characteristics curve (AUC); polytomous discrimination index (PDI)) and evaluated calibration of its risk estimates (observed/expected ratio). RESULTS: The median age of the women in the IETA-3 cohort was 51 (range, 20-85) years and 51% (887/1745) of the women were postmenopausal. Histology showed EC or EIN in 29 (2%) women, endometrial polyps or intracavitary myomas in 1094 (63%), proliferative or secretory endometrium, endometritis, or hyperplasia without atypia in 144 (8%) and endometrial atrophy in 265 (15%) women. The endometrial sample had insufficient material in five (0.3%) cases. In 208 (12%) women who did not undergo endometrial sampling but were followed up for at least 1 year without clinical or ultrasound signs of endometrial malignancy, the outcome was classified as benign. The IETA-1 model had an AUC of 0.81 (95% CI, 0.73-0.89, n = 1745) for discrimination between malignant (EC or EIN) and benign endometrium, and the observed/expected ratio for EC or EIN was 0.51 (95% CI, 0.32-0.82). The model was able to categorize the four histological outcomes with considerable accuracy: the PDI of the model was 0.68 (95% CI, 0.62-0.73) (n = 1532). The IETA-1 model discriminated very well between endometrial atrophy and all other intracavitary uterine conditions, with an AUC of 0.96 (95% CI, 0.95-0.98). Including only patients in whom the endometrium was measurable (n = 1689), the model's AUC was 0.83 (95% CI, 0.75-0.91), compared with 0.62 (95% CI, 0.52-0.73) when using endometrial thickness alone to predict malignancy (difference in AUC, 0.21; 95% CI, 0.08-0.32). In postmenopausal women with measurable endometrial thickness (n = 848), the IETA-1 model gave an AUC of 0.81 (95% CI, 0.71-0.91), while endometrial thickness alone gave an AUC of 0.70 (95% CI, 0.60-0.81) (difference in AUC, 0.11; 95% CI, 0.01-0.20). CONCLUSION: The IETA-1 model discriminates well between benign and malignant conditions in the uterine cavity in patients without abnormal bleeding, but it overestimates the risk of malignancy. It also discriminates well between the four histological outcome categories. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Validation of ADNEX and IOTA two-step strategy and estimation of risk of complications during follow-up of adnexal masses in low-risk population.

OBJECTIVES: The aim is to evaluate the ability of the Assessment of Different NEoplasias in the adneXa model (ADNEX) and the International Ovarian Tumour Analysis (IOTA) two-step strategy to predict malignancy in adnexal masses detected in an outpatient low-risk setting, and to estimate the risk of complications in masses with benign ultrasound morphology managed with clinical and ultrasound follow-up. METHODS: This single center (Hospital Universitari Dexeus Barcelona) study was performed using interim data of the ongoing prospective observational IOTA phase 5 study. The primary aim of the IOTA 5 study is to describe the cumulative incidence of complications during follow-up of adnexal masses classified as benign on ultrasound. Consecutive patients with adnexal masses detected between June 2012 and September 2016 in a private center offering screening for gynecological cancers were included and followed-up until February 2020. Tumors were classified as benign or malignant based on histology (if patients underwent surgery) or outcome of clinical and ultrasound follow-up at 12 (±2) months. Multiple imputation was used when follow-up information was uncertain. The ability of the ADNEX model without CA125 and of the IOTA two-step strategy to distinguish benign from malignant masses was evaluated retrospectively using the prospectively collected data. We describe performance as discrimination (area under the receiver operating characteristic curve, AUC), calibration, classification (sensitivity and specificity) and clinical utility (Net Benefit). In the group of patients with a benign looking mass selected for conservative management we evaluated the occurrence of spontaneous resolution or any mass complication during the first 5 years of follow-up by assessing the cumulative incidence for malignancy, torsion, cyst rupture, or minor mass complications (inflammation, infection, or adhesions) and the time to occurrence of an event. RESULTS: A total of 2654 patients were recruited to the study. After application of exclusion criteria, 2039 patients with a newly detected mass were included for the model validation. 1684 (82.6%) masses were benign, 49 (2.4%) masses were malignant and for 306 (15.0%) masses the outcome was uncertain and imputed. The AUC was 0.95 (95% CI 0.89-0.98) for ADNEX and 0.94 (95% CI 0.88-0.97) for the two-step strategy. Calibration performance could not be meaningfully interpreted due to few malignancies resulting in very wide confidence intervals. The two-step strategy had better clinical utility than ADNEX at malignancy risk thresholds < 3%. 1472 (72%) patients had a mass judged to be benign based on pattern recognition by an experienced ultrasound examiner and were managed with clinical and ultrasound follow-up. In this group, the 5-year cumulative incidence was 66% for spontaneous resolution of the mass (95% CI 63-69), 0% for torsion (95%CI 0-0.002), 0.1% for cyst rupture (<0.1-0.6), 0.2% for a borderline tumor (<0.1-0.6), and 0.2% (0.1-0.6) for invasive malignancy. CONCLUSIONS: The ADNEX model and IOTA two-step strategy performed well to distinguish benign from malignant adnexal masses detected in a low-risk population. Conservative management is safe for masses with benign ultrasound appearance in such a population. This article is protected by copyright. All rights reserved.

Radiomics analysis of ultrasound images to discriminate between benign and malignant adnexal masses with solid ultrasound morphology.

OBJECTIVE: Our primary aim was to identify radiomic ultrasound features that can distinguish benign from malignant adnexal masses with solid ultrasound morphology, and primary invasive from metastatic solid ovarian masses, and to develop ultrasound-based machine learning models that include radiomics features to discriminate between benign and malignant solid adnexal masses. Our secondary aim was to compare the diagnostic performance of our radiomics models with that of the ADNEX model and subjective assessment by an experienced ultrasound examiner. METHODS: This is a retrospective observational single center study. Patients with a histological diagnosis of an adnexal tumor with solid morphology at preoperative ultrasound examination performed between 2014 and 2021 were included. The patient cohort was split into training and validation sets with a ratio of 70:30 and with the same proportion of benign and malignant (borderline, primary invasive and metastatic) tumors in the two subsets. The extracted radiomic features belonged to two different families: intensity-based statistical features and textural features. Models to predict malignancy were built based on a random forest classifier, fine-tuned using 5-fold cross-validation over the training set, and tested on the held-out validation set. The variables used in model building were patient's age, and those radiomic features that were statistically significantly different between benign and malignant adnexal masses (Wilcoxon-Mann-Whitney Test with Benjamini-Hochberg correction for multiple comparisons) and assessed as not redundant based on the Pearson correlation coefficient. We describe discriminative ability as area under the receiver operating characteristics curve (AUC) and classification performance as sensitivity and specificity. RESULTS: 326 patients were identified and 775 preoperative ultrasound images were analyzed. 68 radiomic features were extracted, 52 differed statistically significantly between benign and malignant tumors in the training set, and 18 features were selected for inclusion in model building. The same 52 radiomic features differed statistically significantly between benign, primary invasive malignant and metastatic tumors. However, the values of the features manifested overlap between primary malignant and metastatic tumors and did not differ statistically significantly between them. In the validation set, 25/98 tumors (25.5%) were benign, 73/98 (74.5%) were malignant (6 borderline, 57 primary invasive, 10 metastases). In the validation set, a model including only radiomics features had an AUC of 0.80, and 78% sensitivity and 76% specificity at its optimal risk of malignancy cutoff (68% based on Youden's index). The corresponding results for a model including age and radiomics features were 0.79, 86% and 56% (cutoff 60% based on Youden's method), while those of the ADNEX model were 0.88, 99% and 64% (at 20% malignancy cutoff). Subjective assessment had sensitivity 99% and specificity 72%. CONCLUSIONS: Even though our radiomics models had discriminative ability inferior to that of the ADNEX model, our results are promising enough to justify continued development of radiomics analysis of ultrasound images of adnexal masses. This article is protected by copyright. All rights reserved.

Benign descriptors and ADNEX in two-step strategy to estimate risk of malignancy in ovarian tumors: retrospective validation in IOTA5 multicenter cohort.

OBJECTIVE: Previous work has suggested that the ultrasound-based benign simple descriptors (BDs) can reliably exclude malignancy in a large proportion of women presenting with an adnexal mass. This study aimed to validate a modified version of the BDs and to validate a two-step strategy to estimate the risk of malignancy, in which the modified BDs are followed by the Assessment of Different NEoplasias in the adneXa (ADNEX) model if modified BDs do not apply. METHODS: This was a retrospective analysis using data from the 2-year interim analysis of the International Ovarian Tumor Analysis (IOTA) Phase-5 study, in which consecutive patients with at least one adnexal mass were recruited irrespective of subsequent management (conservative or surgery). The main outcome was classification of tumors as benign or malignant, based on histology or on clinical and ultrasound information during 1 year of follow-up. Multiple imputation was used when outcome based on follow-up was uncertain according to predefined criteria. RESULTS: A total of 8519 patients were recruited at 36 centers between 2012 and 2015. We excluded patients who were already in follow-up at recruitment and all patients from 19 centers that did not fulfil our criteria for good-quality surgical and follow-up data, leaving 4905 patients across 17 centers for statistical analysis. Overall, 3441 (70%) tumors were benign, 978 (20%) malignant and 486 (10%) uncertain. The modified BDs were applicable in 1798/4905 (37%) tumors, of which 1786 (99.3%) were benign. The two-step strategy based on ADNEX without CA125 had an area under the receiver-operating-characteristics curve (AUC) of 0.94 (95% CI, 0.92-0.96). The risk of malignancy was slightly underestimated, but calibration varied between centers. A sensitivity analysis in which we expanded the definition of uncertain outcome resulted in 1419 (29%) tumors with uncertain outcome and an AUC of the two-step strategy without CA125 of 0.93 (95% CI, 0.91-0.95). CONCLUSION: A large proportion of adnexal masses can be classified as benign by the modified BDs. For the remaining masses, the ADNEX model can be used to estimate the risk of malignancy. This two-step strategy is convenient for clinical use. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Thermal Stability and Melting Dynamics of Bimetallic Au@Pt@Au Core-Shell Nanoparticles.

Thermal stability is an important feature of the materials used as components and parts of sensors and other devices of nanoelectronics. Here we report the results of the computational study of the thermal stability of the triple layered Au@Pt@Au core-shell nanoparticles, which are promising materials for H2O2 bi-directional sensing. A distinct feature of the considered sample is the raspberry-like shape, due to the presence of Au nanoprotuberances on its surface. The thermal stability and melting of the samples were studied within classical molecular dynamics simulations. Interatomic forces were computed within the embedded atom method. To investigate the thermal properties of Au@Pt@Au nanoparticles, structural parameters such as Lindemann indexes, radial distribution functions, linear distributions of concentration, and atomistic configurations were calculated. As the performed simulations showed, the raspberry-like structure of the nanoparticle was preserved up to approximately 600 K, while the general core-shell structure was maintained up to approximately 900 K. At higher temperatures, the destruction of the initial fcc crystal structure and core-shell composition was observed for both considered samples. As Au@Pt@Au nanoparticles demonstrated high sensing performance due to their unique structure, the obtained results may be useful for the further design and fabrication of the nanoelectronic devices that are required to work within a certain range of temperatures.

High-Precision Tribometer for Studies of Adhesive Contacts.

Herein, we describe the design of a laboratory setup operating as a high-precision tribometer. The whole design procedure is presented, starting with a concept, followed by the creation of an exact 3D model and final assembly of all functional parts. The functional idea of the setup is based on a previously designed device that was used to perform more simple tasks. A series of experiments revealed certain disadvantages of the initial setup, for which pertinent solutions were found and implemented. Processing and correction of the data obtained from the device are demonstrated with an example involving backlash and signal drift errors. Correction of both linear and non-linear signal drift errors is considered. We also show that, depending on the research interests, the developed equipment can be further modified by alternating its peripheral parts without changing the main frame of the device.

Reproductive outcome after early miscarriage: comparing vaginal misoprostol treatment with expectant management in a planned secondary analysis of a randomized controlled trial.

OBJECTIVE: To compare the reproductive outcome after early miscarriage between women managed expectantly and those treated with vaginal misoprostol. METHODS: This study was a planned secondary analysis of data collected prospectively in a randomized controlled trial comparing expectant management with vaginal misoprostol treatment (single dose of 800 µg) in women with early embryonic or anembryonic miscarriage and vaginal bleeding. The outcome measures were the number of women with a clinical pregnancy conceived within 14 months after complete miscarriage and the outcome of these pregnancies in terms of live birth, miscarriage, ectopic pregnancy and legal termination of pregnancy. The participants replied to a questionnaire sent by post covering their reproductive history ≤ 14 months after the index miscarriage was complete. Supplementary information and data for women who did not return their questionnaire were retrieved from medical records. RESULTS: Of 94 women randomized to misoprostol treatment and 95 allocated to expectant management, 94 and 90 women, respectively, were included for analysis. Information on reproductive outcome was available for 89/94 (95%) and 83/90 (92%) women, respectively. Complete miscarriage without surgical evacuation was achieved within 31 days in 85% (76/89) of the women in the misoprostol group and in 65% (54/83) of those managed expectantly. The proportion of women treated with surgical evacuation was 33% (27/83) in the expectant-management group vs 12% (11/89) in the misoprostol group. At 14 months after the index miscarriage was complete, 75% (67/89) of women treated with misoprostol and 75% (62/83) of those managed expectantly had achieved at least one clinical pregnancy, while 40% (36/89) and 35% (29/83), respectively, had had at least one live birth (mean difference, 5.5% (95% CI, -9.7 to 20.3%)). When considering the outcome of all pregnancies conceived within 14 months after the index miscarriage was complete, 63% (56/89) of women in the misoprostol group and 55% (46/83) of those in the expectant-management group delivered a live baby after a pregnancy (mean difference, 7.5% (95% CI, -7.9 to 22.4%)). CONCLUSION: Women with early miscarriage can be reassured that fertility is similar after misoprostol treatment and expectant management. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Cost-effectiveness of cervical length screening and progesterone treatment to prevent spontaneous preterm delivery in Sweden.

OBJECTIVE: To estimate the cost-effectiveness of strategies to prevent spontaneous preterm delivery (PTD) in asymptomatic singleton pregnancies, using prevalence and healthcare cost data from the Swedish healthcare context. METHODS: We designed a decision analytic model based on the Swedish CERVIX study to estimate the cost-effectiveness of strategies to prevent spontaneous PTD in asymptomatic women with a singleton pregnancy. The model was constructed as a combined decision-tree model and Markov model with a time horizon of 100 years. Four preventive strategies, namely 'Universal screening', 'High-risk-based screening' (i.e. screening of high-risk women only), 'Low-risk-based screening' (i.e. treatment of high-risk population and screening of remaining women) and 'Nullipara screening' (i.e. treatment of high-risk population and screening of nulliparous women only), included second-trimester cervical length (CL) screening by transvaginal ultrasound followed by vaginal progesterone treatment in the case of a short cervix. A fifth preventive strategy involved vaginal progesterone treatment of women with previous spontaneous PTD or late miscarriage but no CL screening ('No screening, treat high-risk group'). For comparison, we used a sixth strategy implying no specific intervention to prevent spontaneous PTD, reflecting the current situation in Sweden ('No screening'). Probabilities for a short cervix (CL ≤ 25 mm; base-case) and for spontaneous PTD at < 33 + 0 weeks and at 33 + 0 to 36 + 6 weeks were derived from the CERVIX study, and probabilities for stillbirth, neonatal mortality and long-term morbidity (cerebral palsy) from Swedish health data registers. Costs were based on Swedish data, except costs for cerebral palsy, which were based on Danish data. We assumed that vaginal progesterone reduces spontaneous PTD before 33 weeks by 30% and spontaneous PTD at 33-36 weeks by 10% (based on the literature). All analyses were from a societal perspective. We expressed the effectiveness of each strategy as gained quality-adjusted life years (QALYs) and presented cost-effectiveness as average (ACER; average cost per gained QALY compared with 'No screening') and incremental (ICER; difference in costs divided by the difference in QALYs for each of two strategies being compared) cost-effectiveness ratios. We performed deterministic and probabilistic sensitivity analysis. The results of the latter are shown as cost-effectiveness acceptability curves. Willingness-to-pay was set at a maximum of 500 000 Swedish krona (56 000 US dollars (USD)), as suggested by the Swedish National Board of Health and Welfare. RESULTS: All interventions had better health outcomes than did 'No screening', with fewer screening-year deaths and more lifetime QALYs. The best strategy in terms of improved health outcomes was 'Low-risk-based screening', irrespective of whether screening was performed at 18 + 0 to 20 + 6 weeks (Cx1) or at 21 + 0 to 23 + 6 weeks (Cx2). 'Low-risk-based screening' at Cx1 was cost-effective, while 'Low-risk-based screening' at Cx2 entailed high costs compared with other alternatives. The ACERs were 2200 USD for 'Low-risk-based screening' at Cx1 and 36 800 USD for 'Low-risk-based screening' at Cx2. Cost-effectiveness was particularly sensitive to progesterone effectiveness and to productivity loss due to sick leave during pregnancy. The probability that 'Low-risk-based screening' at Cx1 is cost-effective compared with 'No screening' was 71%. CONCLUSION: Interventions to prevent spontaneous PTD in asymptomatic women with a singleton pregnancy, including CL screening with progesterone treatment of cases with a short cervix, may be cost-effective in Sweden. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Imaging in gynecological disease (24): clinical and ultrasound characteristics of ovarian mature cystic teratomas.

OBJECTIVE: To describe the clinical and ultrasound features of ovarian mature cystic teratomas (MCTs). METHODS: This was a retrospective study. From the International Ovarian Tumor Analysis (IOTA) database, we identified patients with a histologically confirmed diagnosis of MCT who had undergone transvaginal ultrasound examination between 1999 and 2016 (IOTA phases 1, 2, 3 and 5) in one of five centers. Ultrasound was performed by an experienced examiner who used the standardized IOTA examination technique and terminology. In addition to extracting data from the IOTA database, available two-dimensional grayscale and color or power Doppler images were reviewed retrospectively to identify typical ultrasound features of MCT described previously and detect possible new features using pattern recognition. All images were reviewed by two independent examiners and further discussed with two ultrasound experts to reach consensus. RESULTS: Included in the study were 454 patients with histologically confirmed MCT. Median age was 33 (range, 8-90) years and 66 (14.5%) patients were postmenopausal. Most MCTs were described by the original ultrasound examiner as unilocular (262/454 (57.7%)) or multilocular (70/454 (15.4%)) cysts with mixed echogenicity of cystic fluid (368/454 (81.1%)), acoustic shadowing (328/454 (72.2%)) and no or little vascularization on color Doppler (color score 1, 240/454 (52.9%); color score 2, 123/454 (27.1%)). The median largest lesion diameter was 66 (range, 15-310) mm. A correct preoperative diagnosis of MCT was suggested by the original ultrasound examiner in 372/454 (81.9%) cases. On retrospective review of ultrasound images of 334 MCTs that had quality sufficient for assessment, 'dots and/or lines' and/or 'echogenic white ball' (typical features according to the literature) were present in 271/334 (81.1%) masses. We identified four new ultrasound features characteristic of MCT: 'cotton wool tufts', 'mushroom cap sign', 'completely hyperechogenic lesion' and 'starry sky sign'. At least one classical or novel ultrasound feature was present in 315/334 (94.3%) MCTs. Twenty-nine (8.7%) MCTs manifested vascularized solid tissue, of which seven exhibited no typical features. CONCLUSION: We provide a comprehensive overview of conventional and newly described ultrasound features of MCTs. Only a small proportion of MCTs did not manifest any of the typical features. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Ultrasound features of endometrial pathology in women without abnormal uterine bleeding: results from the International Endometrial Tumor Analysis study (IETA3).

OBJECTIVES: The primary aim of this study was to describe the ultrasound features of various endometrial and other intracavitary pathologies in women without abnormal uterine bleeding (AUB) using the International Endometrial Tumor Analysis (IETA) terminology. The secondary aim was to compare our findings with published data on women with AUB. METHODS: This was a prospective observational study of women presenting at one of seven centers specialized in gynecological ultrasonography, from 2011 until 2018, for indications unrelated to AUB. All patients underwent transvaginal ultrasound using the IETA examination and measurement techniques. Ultrasonography was performed as part of routine gynecological examination or follow-up of non-endometrial pathology, or as part of the work-up before undergoing treatment for infertility, uterine prolapse or ovarian pathology. Ultrasound findings were described using the IETA terminology. Endometrial sampling was performed after the ultrasound scan. The histological endpoints were endometrial atrophy, proliferative or secretory endometrium, endometrial hyperplasia without atypia, endometrial polyp, intracavitary leiomyoma, endometrial intraepithelial neoplasia (EIN), endometrial cancer (EC) and insufficient tissue. The findings in our cohort of women without AUB were compared with those in a published cohort of women with AUB who were examined with transvaginal ultrasound between 2012 and 2015 using the same IETA examination technique and terminology. RESULTS: In this study (IETA3), we included 1745 women without AUB who underwent a standardized transvaginal ultrasound examination followed by either endometrial sampling with histological diagnosis (n = 1537) or at least 1 year of clinical and ultrasound follow-up (n = 208). Of these, 858 (49.2%) women were premenopausal and 887 (50.8%) were postmenopausal. Histology showed the presence of EC and/or EIN in 29 (1.7%) women, endometrial polyps in 1028 (58.9%), intracavitary myomas in 66 (3.8%), proliferative or secretory changes or hyperplasia without atypia in 144 (8.3%), endometrial atrophy in 265 (15.2%) and insufficient tissue in five (0.3%). Most cases of EC or EIN (25/29 (86.2%)) were diagnosed after menopause. The mean endometrial thickness in women with EC or EIN was 11.2 mm (95% CI, 8.9-13.6 mm), being on average 2.4 mm (95% CI, 0.3-4.6 mm) thicker than their benign counterparts. Women with malignant endometrial pathology manifested more frequently non-uniform echogenicity (22/29 (75.9%)) than did those with benign endometrial pathology (929/1716 (54.1%)) (difference, +21.8% (95% CI, +4.2% to +39.2%)). Moderate to abundant vascularization (color score 3-4) was seen in 31.0% (9/29) of cases with EC or EIN compared with 12.8% (220/1716) of those with a benign outcome (difference, +18.2% (95% CI, -0.5% to +36.9%)). Multiple multifocal vessels were recorded in 24.1% (7/29) women with EC or EIN vs 4.0% (68/1716) of those with a benign outcome (difference, +20.2% (95% CI, +4.6% to +35.7%)). A regular endometrial-myometrial junction was seen less frequently in women with EC or EIN (19/29 (65.5%)) vs those with a benign outcome (1412/1716 (82.3%)) (difference, -16.8% (95% CI, -34.2% to +0.6%)). In women with endometrial polyps without AUB, a single dominant vessel was the most frequent vascular pattern (666/1028 (64.8%)). In women with EC, both in those with and those without AUB, the endometrium usually manifested heterogeneous echogenicity, but the endometrium was on average 8.6 mm (95% CI, 5.2-12.0 mm) thinner and less intensely vascularized (color score 3-4: difference, -26.8% (95% CI, -52.2% to -1.3%)) in women without compared to those with AUB. In both pre- and postmenopausal women, asymptomatic endometrial polyps were associated with a thinner endometrium, and they manifested more frequently a bright edge, a regular endometrial-myometrial junction and a single dominant vessel than did polyps in symptomatic women, and they were less intensely vascularized. CONCLUSIONS: We describe the typical ultrasound features of EC, polyps and other intracavitary histologies using IETA terminology in women without AUB. Our findings suggest that the presence of asymptomatic polyps or endometrial malignancy may be accompanied by thinner and less intensely vascularized endometria than their symptomatic counterparts. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Imaging in gynecological disease (23): clinical and ultrasound characteristics of ovarian carcinosarcoma.

OBJECTIVE: To describe the clinical and ultrasound characteristics of ovarian carcinosarcoma. METHODS: This was a retrospective multicenter study. Patients with a histological diagnosis of ovarian carcinosarcoma, who had undergone preoperative ultrasound examination between 2010 and 2019, were identified from the International Ovarian Tumor Analysis (IOTA) database. Additional patients who were examined outside of the IOTA study were identified from the databases of the participating centers. The masses were described using the terms and definitions of the IOTA group. Additionally, two experienced ultrasound examiners reviewed all available images to identify typical ultrasound features using pattern recognition. RESULTS: Ninety-one patients with ovarian carcinosarcoma who had undergone ultrasound examination were identified, of whom 24 were examined within the IOTA studies and 67 were examined outside of the IOTA studies. Median age at diagnosis was 66 (range, 33-91) years and 84/91 (92.3%) patients were postmenopausal. Most patients (67/91, 73.6%) were symptomatic, with the most common complaint being pain (51/91, 56.0%). Most tumors (67/91, 73.6%) were International Federation of Gynecology and Obstetrics (FIGO) Stage III or IV. Bilateral lesions were observed on ultrasound in 46/91 (50.5%) patients. Ascites was present in 38/91 (41.8%) patients. The median largest tumor diameter was 100 (range, 18-260) mm. All ovarian carcinosarcomas contained solid components, and most were described as solid (66/91, 72.5%) or multilocular-solid (22/91, 24.2%). The median diameter of the largest solid component was 77.5 (range, 11-238) mm. Moderate or rich vascularization was found in 78/91 (85.7%) cases. Retrospective analysis of ultrasound images and videoclips using pattern recognition in 73 cases revealed that all tumors had irregular margins and inhomogeneous echogenicity of the solid components. Forty-seven of 73 (64.4%) masses appeared as a solid tumor with cystic areas. Cooked appearance of the solid tissue was identified in 28/73 (38.4%) tumors. No pathognomonic ultrasound sign of ovarian carcinosarcoma was found. CONCLUSIONS: Ovarian carcinosarcomas are usually diagnosed in postmenopausal women and at an advanced stage. The most common ultrasound appearance is a large solid tumor with irregular margins, inhomogeneous echogenicity of the solid tissue and cystic areas. The second most common pattern is a large multilocular-solid mass with inhomogeneous echogenicity of the solid tissue. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Consensus on revised definitions of Morphological Uterus Sonographic Assessment (MUSA) features of adenomyosis: results of modified Delphi procedure.

OBJECTIVES: To evaluate whether the Morphological Uterus Sonographic Assessment (MUSA) features of adenomyosis need to be better defined and, if deemed necessary, to reach consensus on the updated definitions. METHODS: A modified Delphi procedure was performed among European gynecologists with expertise in ultrasound diagnosis of adenomyosis. To identify MUSA features that might need revision, 15 two-dimensional (2D) video recordings (four recordings also included three-dimensional (3D) still images) of transvaginal ultrasound (TVS) examinations of the uterus were presented in the first Delphi round (online questionnaire). Experts were asked to confirm or refute the presence of each of the nine MUSA features of adenomyosis (described in the original MUSA consensus statement) in each of the 15 videoclips and to provide comments. In the second Delphi round (online questionnaire), the results of the first round and suggestions for revision of MUSA features were shared with the experts before they were asked to assess a new set of 2D and 3D still images of TVS examinations and to provide feedback on the proposed revisions. A third Delphi round (virtual group meeting) was conducted to discuss and reach final consensus on revised definitions of MUSA features. Consensus was predefined as at least 66.7% agreement between experts. RESULTS: Of 18 invited experts, 16 agreed to participate in the Delphi procedure. Eleven experts completed and four experts partly finished the first round. The experts identified a need for more detailed definitions of some MUSA features. They recommended use of 3D ultrasound to optimize visualization of the junctional zone. Fifteen experts participated in the second round and reached consensus on the presence or absence of ultrasound features of adenomyosis in most of the still images. Consensus was reached for all revised definitions except those for subendometrial lines and buds and interrupted junctional zone. Thirteen experts joined the online meeting, in which they discussed and agreed on final revisions of the MUSA definitions. There was consensus on the need to distinguish between direct features of adenomyosis, i.e. features indicating presence of ectopic endometrial tissue in the myometrium, and indirect features, i.e. features reflecting changes in the myometrium secondary to presence of endometrial tissue in the myometrium. Myometrial cysts, hyperechogenic islands and echogenic subendometrial lines and buds were classified unanimously as direct features of adenomyosis. Globular uterus, asymmetrical myometrial thickening, fan-shaped shadowing, translesional vascularity, irregular junctional zone and interrupted junctional zone were classified as indirect features of adenomyosis. CONCLUSION: Consensus between gynecologists with expertise in ultrasound diagnosis of adenomyosis was achieved regarding revised definitions of the MUSA features of adenomyosis and on the classification of MUSA features as direct or indirect signs of adenomyosis. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Massive and Topological Surface States in Tensile-Strained HgTe.

Magneto-transport measurements on gated high-mobility heterostructures containing a 60 nm layer of tensile-strained HgTe, a three-dimensional topological insulator, show well-developed Hall quantization from surface states both in the n- as well as in the p-type regime. While the n-type behavior is due to transport in the topological surface state of the material, we find from 8-orbital k·p calculations that the p-type transport results from massive Volkov-Pankratov states. Their formation prevents the Dirac point and thus the p-conducting topological surface state from being accessible in transport experiments. This interpretation is supported by low-field magneto-transport experiments demonstrating the coexistence of n-conducting topological surface states and p-conducting Volkov-Pankratov states at the relevant gate voltages.

Electron-Hole Scattering Limited Transport of Dirac Fermions in a Topological Insulator.

We have experimentally investigated the effect of electron temperature on transport in the two-dimensional Dirac surface states of the three-dimensional topological insulator HgTe. We have found that around the minimal conductivity point, where both electrons and holes are present, heating the carriers with a DC current results in a nonmonotonic differential resistance of narrow channels. We have shown that the observed initial increase in resistance can be attributed to electron-hole scattering, while the decrease follows naturally from the change in Fermi energy of the charge carriers. Both effects are governed dominantly by a van Hove singularity in the bulk valence band. The results demonstrate the importance of interband electron-hole scattering in the transport properties of topological insulators.

Second-trimester transvaginal ultrasound measurement of cervical length for prediction of preterm birth: a blinded prospective multicentre diagnostic accuracy study.

OBJECTIVE: To estimate the diagnostic performance of sonographic cervical length for the prediction of preterm birth (PTB). DESIGN: Prospective observational multicentre study. SETTING: Seven Swedish ultrasound centres. SAMPLE: A cohort of 11 456 asymptomatic women with a singleton pregnancy. METHODS: Cervical length was measured with transvaginal ultrasound at 18-20 weeks of gestation (C×1) and at 21-23 weeks of gestation (C×2, optional). Staff and participants were blinded to results. MAIN OUTCOME MEASURES: Area under receiver operating characteristic curve (AUC), sensitivity, specificity, positive and negative predictive values (PPV and NPV), positive and negative likelihood ratios (LR+ and LR-), number of false-positive results per true-positive result (FP/TP), number needed to screen to detect one PTB (NNS) and prevalence of 'short' cervix. RESULTS: Spontaneous PTB (sPTB) at <33 weeks of gestation occurred in 56/11 072 (0.5%) women in the C×1 population (89% white) and in 26/6288 (0.4%) in the C×2 population (92% white). The discriminative ability of shortest endocervical length was better the earlier the sPTB occurred and was better at C×2 than at C×1 (AUC to predict sPTB at <33 weeks of gestation 0.76 versus 0.65, difference in AUC 0.11, 95% CI 0.01-0.23). At C×2, the shortest endocervical length of ≤25 mm (prevalence 4.4%) predicted sPTB at <33 weeks of gestation with sensitivity 38.5% (10/26), specificity 95.8% (5998/6262), PPV 3.6% (10/274), NPV 99.7% (5988/6014), LR+ 9.1, LR- 0.64, FP/TP 26 and NNS 629. CONCLUSIONS: Second-trimester sonographic cervical length can identify women at high risk of sPTB. In a population of mainly white women with a low prevalence of sPTB its diagnostic performance is at best moderate. TWEETABLE ABSTRACT: Cervical length screening to predict preterm birth in a white low-risk population has moderate performance.

Psychological impact of early miscarriage and client satisfaction with treatment: comparison between expectant management and misoprostol treatment in a randomized controlled trial.

OBJECTIVES: To compare the short- and long-term emotional distress (grief, anxiety and depressive symptoms) after early miscarriage and satisfaction with treatment between women randomized to expectant management vs vaginal misoprostol treatment. METHODS: This was a preplanned analysis of data collected during a randomized controlled trial comparing expectant management with misoprostol treatment in women with early anembryonic or embryonic miscarriage and vaginal bleeding. If the miscarriage was not complete on day 31 after inclusion, surgical evacuation was recommended. The main outcomes were levels of anxiety and grief, depressive symptoms and client satisfaction with the treatment, which were assessed using the following validated psychometric self-assessment instruments: Spielberger State-Trait Anxiety Inventory (STAI, Form Y), Perinatal Grief Scale (PGS), Montgomery-Åsberg Depression Rating Scale (MADRS-S; self-reported version) and Client Satisfaction Questionnaire (CSQ-8). All women were assessed at four timepoints: on the day of randomization, on the day when the miscarriage was judged to be complete, and at 3 months and 14 months after complete miscarriage. The psychometric and client satisfaction scores were compared between the misoprostol group and the expectant-management group at each assessment. Analysis was performed by the intention-to-treat principle. RESULTS: Ninety women were randomized to expectant management and 94 to misoprostol treatment. The psychometric and client satisfaction scores were similar in the two treatment groups at all assessment timepoints. At inclusion, 41% (35/86) of the women managed expectantly and 37% (34/92) of those treated with misoprostol had a STAI-state score of > 46 ('high level of anxiety'), and 9% (8/86) and 10% (9/91), respectively, had symptoms of moderate or severe depression (MADRS-S score ≥ 20). In both treatment groups, symptom scores for anxiety and depression were significantly higher at inclusion than after treatment and remained low until 14 months after complete miscarriage. Grief reactions were mild in both groups, with a median PGS score of 40.0 at 3 months and 37.0 at 14 months after complete miscarriage in both treatment groups. Four women treated with misoprostol and two women managed expectantly had a PGS score of > 90 (indicating deep grief) 3 months after complete miscarriage, while one woman managed expectantly had a PGS score of > 90 14 months after complete miscarriage. Women in both treatment groups were satisfied with their management, as indicated by a median CSQ-8 score of > 25 at each assessment. More than 85% of participants in each of the two groups reported that they would recommend the treatment they received to a friend. CONCLUSIONS: The psychological response to and recovery after early miscarriage did not differ between women treated with misoprostol and those managed expectantly. Satisfaction with treatment was high in both treatment groups. Our findings support patient involvement when deciding on the management of early miscarriage. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Terms, definitions and measurements to describe sonographic features of lymph nodes: consensus opinion from the Vulvar International Tumor Analysis (VITA) group.

In centers with access to high-end ultrasound machines and expert sonologists, ultrasound is used to detect metastases in regional lymph nodes from melanoma, breast cancer and vulvar cancer. There is, as yet, no international consensus on ultrasound assessment of lymph nodes in any disease or medical condition. The lack of standardized ultrasound nomenclature to describe lymph nodes makes it difficult to compare results from different ultrasound studies and to find reliable ultrasound features for distinguishing non-infiltrated lymph nodes from lymph nodes infiltrated by cancer or lymphoma cells. The Vulvar International Tumor Analysis (VITA) collaborative group consists of gynecologists, gynecologic oncologists and radiologists with expertise in gynecologic cancer, particularly in the ultrasound staging and treatment of vulvar cancer. The work herein is a consensus opinion on terms, definitions and measurements which may be used to describe inguinal lymph nodes on grayscale and color/power Doppler ultrasound. The proposed nomenclature need not be limited to the description of inguinal lymph nodes as part of vulvar cancer staging; it can be used to describe peripheral lymph nodes in general, as well as non-peripheral (i.e. parietal or visceral) lymph nodes if these can be visualized clearly. The association between the ultrasound features described here and histopathological diagnosis has not yet been established. VITA terms and definitions lay the foundations for prospective studies aiming to identify ultrasound features typical of metastases and other pathology in lymph nodes and studies to elucidate the role of ultrasound in staging of vulvar and other malignancies. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Imaging in gynecological disease (22): clinical and ultrasound characteristics of ovarian embryonal carcinomas, non-gestational choriocarcinomas and malignant mixed germ cell tumors.

OBJECTIVE: To describe the clinical and ultrasound characteristics of three types of rare malignant ovarian germ cell tumor: embryonal carcinoma, non-gestational choriocarcinoma and malignant mixed germ cell tumor. METHODS: This was a retrospective multicenter study. From the International Ovarian Tumor Analysis (IOTA) database, we identified patients with a histological diagnosis of ovarian embryonal carcinoma, non-gestational choriocarcinoma or malignant mixed germ cell tumor, who had undergone preoperative ultrasound examination by an experienced ultrasound examiner between 2000 and 2020. Additional patients with the same histology were identified from the databases of the departments of gynecological oncology in the participating centers. All tumors were described using IOTA terminology. Three examiners reviewed all available ultrasound images and described them using pattern recognition. RESULTS: One patient with embryonal carcinoma, five patients with non-gestational ovarian choriocarcinoma and seven patients with ovarian malignant mixed germ cell tumor (six primary tumors and one recurrence) were identified. Seven patients were included in the IOTA studies and six patients were examined outside of the IOTA studies. The median age at diagnosis was 26 (range, 14-77) years. Beta-human chorionic gonadotropin levels were highest in non-gestational choriocarcinomas and alpha-fetoprotein levels were highest in malignant mixed germ cell tumors. Most tumors were International Federation of Gynecology and Obstetrics (FIGO) Stage I (9/12 (75.0%)). All tumors were unilateral, and the median largest diameter was 129 (range, 38-216) mm. Of the tumors, 11/13 (84.6%) were solid and 2/13 (15.4%) were multilocular-solid; 9/13 (69.2%) manifested abundant vascularization on color Doppler examination. Using pattern recognition, the typical ultrasound appearance was a large solid tumor with inhomogeneous echogenicity of the solid tissue and often dispersed cysts which, in most cases, were small and irregular. Some tumors had smooth contours while others had irregular contours. CONCLUSIONS: A unilateral, large solid tumor with inhomogeneous echogenicity of the solid tissue and with dispersed small cystic areas in a young woman should raise the suspicion of a rare malignant germ cell tumor. This suspicion can guide the clinician to test tumor markers specific for malignant germ cell tumors. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.