Accuracy of ultrasonography performed by examiners with varied training and experience in predicting specific pathology of adnexal masses.

OBJECTIVES: To assess the diagnostic performance of subjective assessment by Level II ultrasound examiners in predicting the specific histology of adnexal masses. METHODS: The women included in this prospective multicenter cross-sectional study were older than 16 years of age and had at least one adnexal mass. They underwent transvaginal sonography (TVS) performed by Level II examiners, all of whom were familiar with the International Ovarian Tumor Analysis (IOTA) group definitions of ultrasound features of ovarian masses. The final outcome was histology. Specific diagnoses were categorized into 16 groups. Agreement between subjective assessment and final histology was measured using unweighted kappa coefficients. Sensitivities and specificities were obtained for subjective assessment. RESULTS: Of the 1279 women who underwent TVS, 313 were included in the final analysis. Overall agreement (16 × 16 table) between subjective assessment and histology was moderate, with a Cohen's kappa coefficient of 0.59 (95% CI, 0.53-0.65). The specificity of subjective assessment ranged between 91% and 100% for all histological subgroups. Highest sensitivities were achieved in the diagnosis of simple cysts (100% (95% CI, 61-100%)), hydrosalpinges (100% (95% CI, 34-100%)), mature teratomas (88% (95% CI, 74-96%)), endometriomas (75% (95% CI, 61-85%)), ovarian fibromas (88% (95% CI, 47-100%)), tubo-ovarian abscesses (88% (95% CI, 47-100%)) and serous cystadenocarcinomas (82% (95% CI, 66-93%)). Serous cystadenomas were misdiagnosed most commonly (40.5%). The sensitivity of subjective assessment in diagnosing adnexal torsion was 54% (95% CI, 25-81%); the 17 confirmed and/or suspected cases of adnexal torsion were not included in the 313 cases examined and analyzed for diagnostic performance. CONCLUSION: Overall, subjective assessment by Level II examiners was good for the detection of simple cysts, endometriomas, mature teratomas, hydrosalpinges, fibroma, tubo-ovarian abscess and serous cystadenocarcinomas.

Role of the glucose tolerance test as a predictor of preeclampsia.

OBJECTIVE: To determine whether oral glucose tolerance tests (OGTT) play a role as predictors of preeclampsia (PET) in pregnant women. METHODS: A retrospective case-control study was conducted in 2,002 singleton pregnancies that had a uterine artery (UtA) Doppler at 22-25 weeks and an OGTT. The UtA Doppler and OGTT were adjusted based on maternal characteristics, and the results were expressed as multiples of the expected normal median and compared between groups. Logistic regression analysis was used to determine whether maternal characteristics, OGTT, and UtA Doppler significantly contribute to the prediction of early- (<34 weeks), intermediate- (34-37 weeks), or late-onset (>37 weeks) PET. The performance of the screening was determined by ROC curves. RESULTS: Women who developed PET were characterized by an older maternal age, an increased body mass index, and an altered UtA Doppler. The group with intermediate-onset PET was the only one associated with higher 2-hour OGTT levels compared to controls. Combined models were developed via logistic regression analysis using maternal characteristics, UtA Doppler, and OGTT to predict PET. These combined models were able to detect around 74, 42, and 21% of women who later developed early-, intermediate-, or late-onset PET, respectively, with only a 5% false-positive rate. CONCLUSIONS: This study shows that the combination of maternal characteristics, second-trimester UtA Doppler, and OGTT is a predictor of the development of PET in healthy pregnant women.

External validation of models and simple scoring systems to predict miscarriage in intrauterine pregnancies of uncertain viability.

STUDY QUESTION: Does a logistic regression model and scoring system to predict viability of an intrauterine pregnancy of uncertain viability (PUV) perform as well in an independent patient group as the original patient group? SUMMARY ANSWER: The model and scoring system showed good performance on external validation confirming their value for the prediction of miscarriage/viability in PUV patients up to 11-14 weeks of gestation. WHAT IS KNOWN ALREADY: Several individual ultrasound and demographic factors have been described as predictors for miscarriage. A logistic regression model and simple scoring system using basic clinical and ultrasound features, such as maternal age, bleeding score, mean gestational sac diameter (MSD) and presence or absence of yolk sac, have been developed to allow patient-specific prediction of viability of PUV beyond the first trimester. STUDY DESIGN, SIZE, DURATION: Prospective observational external validation cohort study in two inner city early pregnancy assessment units over a period of 18 months. PARTICIPANTS/MATERIALS, SETTING, METHODS: All consecutive women with a PUV were recruited. Ultrasound (mean sac diameter and presence of yolk sac) and demographic variables (maternal age, bleeding score and gestational age) were noted. The outcome measure was first trimester (11-14 week) viability. Women with unknown first trimester outcome were excluded. Receiver operating characteristic (ROC) curves and calibration plots were constructed. Test performance was compared with the original development data set. A new model and scoring system, which did not include gestational age, was built and evaluated. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 575 women who were recruited, first trimester outcome was known for 89.2% (n = 513). The model could only be validated in 400 patients, due to missing values in model variables and outcome. The model predicted viability with an area under the ROC curve (AUC) of 0.845 [95% confidence interval (CI), 0.806-0.884] compared with 0.774 (95% CI, 0.701-0.848) in the original study. The AUC for the scoring system was 0.832 (95% CI, 0.792-0.872) compared with 0.771 (95% CI, 0.698-0.844) from the original study data set. The new model and the scoring system, excluding gestational age, could be evaluated on 503 patients and resulted in an AUC of 0.801 (95% CI, 0.765-0.841) for the model and 0.773 (95% CI, 0.733-0.812) for the scoring system. LIMITATIONS, REASONS FOR CAUTION: Approximately 22% of patients could not be validated due to missing variables and for 11% of patients the first trimester outcome was unknown. WIDER IMPLICATIONS OF THE FINDINGS: Both the model and the scoring system showed excellent performance on external validation confirming their generalizability and utility in prediction of viability beyond the first trimester in clinical practice. An advantage of the mathematical models original Mo and new Mn and scoring systems original SSo and new SSn is that they can provide women with an individualized probability of the viability of their pregnancy using only demographic information, symptoms and TVS findings. Furthermore, the risk of miscarriage can be given immediately following examination. STUDY FUNDING/COMPETING INTEREST(S): T.B. is supported by the Imperial Healthcare NHS Trust NIHR Biomedical Research Centre. This research is supported by Research Council KUL GOA MaNet, iMinds 2012, Belgian Federal Science Policy Office IUAP P719. VVB is a postdoctoral fellow of the Research Foundation - Flanders (FWO). There are no conflicts of interest.

Multicentre external validation of IOTA prediction models and RMI by operators with varied training.

BACKGROUND: Correct characterisation of ovarian tumours is critical to optimise patient care. The purpose of this study is to evaluate the diagnostic performance of the International Ovarian Tumour Analysis (IOTA) logistic regression model (LR2), ultrasound Simple Rules (SR), the Risk of Malignancy Index (RMI) and subjective assessment (SA) for preoperative characterisation of adnexal masses, when ultrasonography is performed by examiners with different background training and experience. METHODS: A 2-year prospective multicentre cross-sectional study. Thirty-five level II ultrasound examiners contributed in three UK hospitals. Transvaginal ultrasonography was performed using a standardised approach. The final outcome was the surgical findings and histological diagnosis. To characterise the adnexal masses, the six-variable prediction model (LR2) with a cutoff of 0.1, the RMI with cutoff of 200, ten SR (five rules for malignancy and five rules for benignity) and SA were applied. The area under the curves (AUCs) for performance of LR2 and RMI were calculated. Diagnostic performance measures for all models assessed were sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), and the diagnostic odds ratio (DOR). RESULTS: Nine-hundred and sixty-two women with adnexal masses underwent transvaginal ultrasonography, whereas 255 had surgery. Prevalence of malignancy was 29% (49 primary invasive epithelial ovarian cancers, 18 borderline ovarian tumours, and 7 metastatic tumours). The AUCs for LR2 and RMI for all masses were 0.94 (95% confidence interval (CI): 0.89-0.97) and 0.90 (95% CI: 0.83-0.94), respectively. In premenopausal women, LR2-RMI difference was 0.09 (95% CI: 0.03-0.15) compared with -0.02 (95% CI: -0.08 to 0.04) in postmenopausal women. For all masses, the DORs for LR2, RMI, SR+SA (using SA when SR inapplicable), SR+MA (assuming malignancy when SR inapplicable), and SA were 62 (95% CI: 27-142), 43 (95% CI: 19-97), 109 (95% CI: 44-274), 66 (95% CI: 27-158), and 70 (95% CI: 30-163), respectively. CONCLUSION: Overall, the test performance of IOTA prediction models and rules as well as the RMI was maintained in examiners with varying levels of training and experience.

Rationalizing the management of pregnancies of unknown location: temporal and external validation of a risk prediction model on 1962 pregnancies.

STUDY QUESTION: Can we accurately define a group of pregnancies of unknown location (PULs) as low risk in order to safely reduce follow-up for these pregnancies and allocate resources to pregnancies at an increased risk of being ectopic? SUMMARY ANSWER: Prediction model M4 classified around 70% of PULs as low risk, of which around 97% were later characterized as failed PULs or intrauterine pregnancies (IUPs), while still classifying 88% of ectopic pregnancies as high risk. WHAT IS KNOWN ALREADY: Depending on the level of suspicion of ectopic pregnancy (EP), women with a PUL receive a lengthy follow-up in order to confirm the location and viability of the pregnancy. STUDY DESIGN, SIZE, DURATION: A multi-centre diagnostic accuracy study of 1962 patients was carried out between 2003 and 2007 for retrospective temporal validation and between 2009 and 2011 for prospective external validation. The reference standard is the final characterization of PUL as failed pregnancies or IUPs (low risk), or as ectopic pregnancies (high risk). M4 is a multinomial logistic regression model based on the serum human chorionic gonadotrophin (hCG) levels at presentation and 48 h later. PARTICIPANTS/MATERIALS, SETTING, METHODS: Temporal validation data from 1341 PULs collected at St George's Hospital in London were available, of which 53% were failed, 39% were intrauterine and 8% were ectopic pregnancies. External validation data from 621 PULs collected at four other London-based teaching hospitals were available, of which 63% were failed, 22% were intrauterine and 15% were ectopic pregnancies. MAIN RESULTS AND THE ROLE OF CHANCE: The EP rate varied between 8 and 16% across the five hospitals. At St George's, 980 [73.1%, 95% confidence interval (CI): 70.5-75.4] PULs were considered low risk. Of these, 963 were failed PULs or IUPs (98.3%, 95% CI: 97.2-98.9) and 17 were ectopic pregnancies. At the other four hospitals, 62-75% were considered low risk, with 96-98% of these turning out to be failed PUL or IUP. Eighty-five percent (95% CI: 76.8-90.2) of the ectopic pregnancies were considered high risk at St George's, compared with 80-92% in the other hospitals. LIMITATIONS, REASONS FOR CAUTION: Of total, 120 patients had been excluded due to loss to follow-up, and a further 102 patients because of missing hCG levels due to differences in local clinical practice. There are variations in the definition of a PUL used in different countries. WIDER IMPLICATIONS OF THE FINDINGS: The suggested protocol could safely reduce the follow-up in the majority of PUL such that units could increase the focus on women at a risk of complications. This would lead to a change in the management of the majority of women with a PUL and a more efficient use of resources. At the end of the manuscript, we provide a link to enable clinicians to use the protocol. STUDY FUNDING/COMPETING INTEREST(S): B.V.C. is supported by a postdoctoral fellowship from the Research Foundation Flanders (FWO). K.V.H. is supported by a fellowship from the Flanders' Agency for Innovation by Science and Technology (IWT-Vlaanderen), by the Research Council KU Leuven (GOA MaNet), by the Flemish Government (iMinds) and by the Belgian Federal Science Policy Office (IUAP P7/DYSCO). T.B. is supported by the Imperial Healthcare NHS Trust NIHR Biomedical Research Centre. No competing interests are declared.

Explosive backpacks in old termite workers.

By nature, defensive behavior is risky. In social insects, such behavior is more likely to occur in individuals whose potential for other tasks is diminished. We show that workers of the termite Neocapritermes taracua develop an exceptional two-component suicidal apparatus consisting of copper-containing protein crystals, stored in external pouches, and internal salivary glands. During aggressive encounters, their bodies rupture, and the crystals react with the salivary gland secretion to produce a toxic droplet. Both the amount of defensive substances and the readiness to explode increase with workers' age, as their food-collecting ability declines.

Do pocket-sized ultrasound machines have the potential to be used as a tool to triage patients in obstetrics and gynecology?

OBJECTIVES: To evaluate the performance and potential impact on patient management of a pocket-sized ultrasound machine (PUM) in comparison to high-specification ultrasound machines (HSUM). METHODS: This was an observational cohort study with 204 unselected patients in three categories: 1) women with pain and bleeding in early pregnancy (101 patients); 2) women presenting for routine obstetric ultrasound assessment (53 patients); 3) women with possible gynecological pathology (50 patients). Scans were carried out transabdominally using a PUM. A second operator repeated the examination transvaginally and/or transabdominally, depending on the clinical indication, using an HSUM. The operators were blind to each other's findings. RESULTS: In the early pregnancy group, there was good to very good agreement between the PUM and HSUM for identifying the presence or absence of an embryo, gestational sac, fetal heart motion, pregnancy location and final diagnostic outcome (kappa coefficients, 0.844, 0.843, 0.729, 0.785 and 0.812, respectively; P < 0.0001). In the obstetric ultrasound group there was good to very good agreement for fetal presentation, placental location and placental position (kappa coefficients, 0.924, 0.924 and 0.647, respectively; P < 0.0001). In the gynecological pathology group, there was very good agreement for final diagnosis and type of ovarian mass (low risk or complex) (kappa coefficients, 0.846 and 0.930, respectively; P < 0.0001). For the measured continuous variables, there was close agreement for crown-rump length, mean sac diameter, femur length and mean diameter of an ovarian mass, but not for endometrial thickness. Neither patient demographics (age, body mass index, ethnicity) nor operator experience and familiarity with a PUM had an impact on agreement between the two machines. If a PUM had been the only equipment available for an initial assessment, only two cases would have led to a suboptimal patient management plan. CONCLUSION: The findings and final diagnosis in the three study groups were similar for both a PUM used transabdominally and an HSUM used transvaginally and/or transabdominally.

High-throughput axial MALDI-TOF MS using a 2-kHz repetition rate laser.

A high-throughput axial MALDI-TOF mass spectrometer utilizing a laser with a 2-kHz pulse repetition-rate was constructed and tested. This fast mass spectrometer provided a data acquisition rate 10 times faster than a commercially available (200 Hz) axial mass spectrometer, while maintaining comparable limits of detection (200 amol of Glu fib peptide). Mass resolution, only slightly less than the commercial instrument (10 000 vs 14 000), was sufficient for baseline resolution of isotopic clusters of peptides with m/z <2700. A new method of mass calibration, which combined a limited number of internal and external standards, provided the same 15 ppm mass accuracy over the entire sample plate on either instrument. Implementing the 2-kHz laser required a faster data acquisition system and high-voltage pulse electronics, together with a novel strategy for rapid sample plate movements during acquisition, to achieve a sample analysis rate of up to 2 spots/s (with 800 shots/spot). The overall performance of the fast MALDI-TOF MS instrument was demonstrated by the acquisition, in 12 min, of an LC-MS data set from a plate of 625 fractions collected during LC separation of an 16O/18O differentially labeled proteomic sample of a tryptic digest of an E. coli lysate.

Capillary electrophoresis--matrix-assisted laser desorption/ionization time-of-flight mass spectrometry using a vacuum deposition interface.

An improved vacuum deposition interface for coupling capillary electrophoresis with MALDI-TOF MS has been developed. Liquid samples consisting of analyte and matrix were deposited on a moving tape in the evacuated source chamber of a TOF mass spectrometer, enabling 24 h of uninterrupted analysis. The vacuum deposition procedure was compared with the dried-droplet method, and it was found that vacuum deposition generated significantly more reproducible signal intensity, eliminating the need for "sweet spot" searching. A concentration detection limit in the low-nanomolar range has been achieved with a low-attomole amount of sample consumed per spectrum. In addition, ion suppression caused by hydrophobicity differences in the analytes was reduced. To minimize ion suppression further, separation prior to MALDI MS analysis was employed. The performance of capillary electrophoresis (CE)-MALDI-TOF MS using the vacuum deposition interface was evaluated with a peptide mixture injected at low-femtomole levels. All peptides were baseline resolved with separation efficiencies in the range of 250000-400000 plates/m (2-3-s band half-width), demonstrating the high separation efficiency of the CE-MALDI MS coupling. A fast (approximately 40 s) CE separation of a mixture of angiotensins was found to reduce significantly ion suppression and enable trace level detection. It was also shown, for the analysis of an enolase digest, that sequence coverage of 65% was obtained using CE separation compared to 52% using step-elution solid-phase extraction and 44% in the control experiment using an unseparated mixture.

On-line MALDI-TOF MS using a continuous vacuum deposition interface.

In this work, a new interface for continuous on-line MALDI-TOF MS is presented. The sample, mixed with a suitable matrix, was transported into the evacuated source chamber of the mass spectrometer at liquid flow rates of 100-400 nL/min. The liquid sample matrix was deposited on a rotating quartz wheel and transported to the repeller, where laser desorption took place. Rapid evaporation of the solvent (water or methanol) on the surface of the wheel resulted in formation of a thin, approximately 50-micron-wide, sample trace. Scanning electron microscopic photographs of the vacuum-dried trace revealed the deposited material to consist of an amorphous film. Furthermore, sample uniformity along the trace, in conjunction with its narrow width, resulted in excellent signal reproducibility, with detection limits in the attomole range. The interface permitted the on-line coupling of microcolumn separation techniques with MALDI MS, as demonstrated in the capillary electrophoresis MALDI-TOF MS analysis of a 12-peptide mixture. The approach offers the potential for rapid separation and trace analysis of complex mixtures.

Laser photodissociation of insulin ions generated by matrix-assisted laser desorption.

A novel method for studying the ionization step of matrix-assisted laser desorption/ionization (MALDI) is demonstrated. A 193-nm pulse from an ArF excimer laser is used to photodissociate a portion of a plume of insulin ions generated by MALDI. Laser photodissociation (LPD) creates a "hole", i.e., a negative spike in the insulin peak in the time-of-flight (TOF) mass spectrum. The position of the hole in the mass spectrum provides useful measurements of the characteristics (position, time, and velocity) of insulin ions shortly after their creation. Although the performance of the method can be further improved, the data obtained could be used to refine our current understanding of MALDI and to improve the resolution of MALDI-TOFMS.

Characterization of Nonbonded Poly(ethylene oxide) Coating for Capillary Electrophoresis via Continuous Monitoring of Electroosmotic Flow.

We examined changes in a poly(ethylene oxide) (PEO) coating by continuously monitoring the electroosmotic flow (EOF) in a fused-silica capillary during electrophoresis. An imaging CCD camera was used to follow the motion of a fluorescent neutral marker zone along the length of the capillary. The PEO coating was shown to reduce the velocity of EOF by more than 1 order of magnitude compared to a bare capillary at pH 7.0. However, it did not reduce EOF efficiently at pH 8.2. The coating protocol was important, especially at an intermediate pH of 7.7. Capillary reconditioning with an acidified solution of PEO was necessary in order to create a stable and efficient coating. In all cases we observed a gradual increase of EOF during extended runs, suggesting that the coating is slowly being degraded. The increase of pH in the cathodic (detection-end) buffer reservoir beyond pH ∼8.0, e.g., as a result of electrolysis, had a large impact on the stability of the coating. This phenomenon may be used for the efficient and fast regeneration of the column surface and provides a simpler and more reliable alternative to pressure flushing of the capillary.

Measuring life event stress in the lives of college students: the Undergraduate Stress Questionnaire (USQ).

We describe the development of the Undergraduate Stress Questionnaire (USQ), a life events checklist designed to measure stress among undergraduates. Several studies demonstrate the USQ's validity. The USQ correlates positively with physical symptoms and negatively with mood. Students rated the USQ as the most complete and accurate of four different life events questionnaires. In a panel study, the USQ closely tracked subjective reports of stress, both during the term and finals week. The USQ predicted symptoms more reliably than three other stress measures, controlling for negative affect. Students waiting in the college infirmary score higher on the USQ than students socializing on campus. Finally, we compare the checklist format to subjective scaling, and show the superiority of the checklist version. We discuss the usefulness of the USQ in terms of validity, representativeness, adaptability, brevity, and low confounding with negative affect.

Screening of pulmonary hypertension in chronic obstructive pulmonary disease and silicosis by discriminant functions.

The aim of our prospective multicentric study was to develop a screening method for pulmonary hypertension in patients with chronic lung diseases. We investigated 710 patients in 10 hospitals: 315 males and 109 females with chronic obstructive pulmonary disease, and 286 males with silicosis. Manifest pulmonary hypertension was defined as pulmonary artery pressure greater than 20 mmHg (2.7 kPa) at rest. The multivariate statistical method used was a stepwise discriminant analysis. In males with chronic obstructive pulmonary disease, the diameter of the right descending pulmonary artery, forced expiratory volume in one second (FEV1) arterial oxygen tension (PaO2) at rest, and age turned out to be relevant for discrimination of groups with and without manifest pulmonary hypertension. For females the FEV1/FVC (forced vital capacity) ratio replaced the absolute value of FEV1 in the calculated discriminant function. In females, sensitivity and specificity were below 80%. In males, both were distinctly above 80%. In silicosis, the diameter of the right descending pulmonary artery was much less important, since it could frequently not be measured precisely. In these cases, precision of the prediction of about 80% could only be obtained by combined evaluation of spirometry, PaO2 during exercise, and body plethysmography. The calculated discriminant functions are appropriate for screening patients with risk of pulmonary hypertension. For different chronic lung diseases, and for both sexes, different combinations of parameters are relevant. The method is recommended to select patients who should undergo an invasive examination of pulmonary haemodynamics.

[Spontaneous pneumothorax in chronic obstructive lung disease]. / Der Spontanpneumothorax bei chronisch obstruktiver Lungenkrankheit.

In the present study the aims were to analyse the difference in various treatment, complications and recurrence rates between patients with spontaneous pneumothorax and those associated with chronic obstructive lung disease (COLD). We made a retrospective analysis with regard to the therapy of all patients with spontaneous pneumothorax who were treated in the district lung hospital Lostau from 1. Jan 1986 to 31. Dec 1988 (171 patients, men: 136, women: 35). 45 patients suffered from a COLD (men: 42, women: 3). 3 methods of the treatment were set in: 1. conservative management by expectant observation, 2. the aspiration once or repeatedly with the pneumothorax apparatus and 3. the rubber-tube drainage. We consider the aspiration of spontaneous pneumothorax with pneumothorax apparatus as an effective method, which is not very burdensome for the patients. It is our opinion that the practice in patients with a COLD is more active than this in other patients, in form of the rubber-tube drainage.

[Reexpansion edema of the lung as a complication of the treatment of a spontaneous pneumothorax]. / Das Reexpansions-Odem der Lunge als Komplikation der Therapie eines Spontanpneumothorax.

It is reported on a 51-year-old patient in whom a reexpansion edema of the lung occurred after treatment of a pneumothorax. As a cause of the development of this complication, a high negative intrathoracic pressure is of high importance. Further pathogenetic factors are discussed.

[Internal medicine treatment of pleural empyema]. / Die internistische Behandlung des Pleuraempyems.

We made a retrospective analysis with regard to the bacteriology and to the therapy of all patients with pleural empyema who were treated in the district lung hospital from 1. 1. 1982-31. 12. 1986. 92 patients had a non-specific empyema, only 3 patients had a specific empyema. All patients were aspirated repeatedly with physiological saline solution instillation and antimicrobic drug instillation in the pleural cavity. This daily aspiration and lavage was successfully in 65 patients. This method was ineffective in 30 patients. We treated 7 patients of this group by the closed drainage (rubber-tube drain), in 4 patients successfully. 3 patients had to be treated by a surgical operation. An insufficient obliteration of the cavity of empyema occurred also in 23 patients of this group. A systematic daily aspiration for a longer time led to regression of the cavity in 4 cases, whereas a surgical operation was necessary in 19 patients. We consider the daily aspiration and lavage as an effective method in patients in early acute stages of empyema.

Observations on the morphology of the hair follicle mites (Acari: Demodicidae) from Cervus elaphus L., 1758 including description of Demodex acutipes sp. n.

Morphology of Demodex acutipes sp. n. and Demodex sp. parasitizing the red deer, Cervus elaphus L., 1758 is described and diagnostic characters of three Demodex species from this host are compared.