Measurement of the cardiac time intervals of the fetal ECG utilising a computerised algorithm: A retrospective observational study.

Objective: Establish whether the reliable measurement of cardiac time intervals of the fetal ECG can be automated and to address whether this approach could be used to investigate large datasets. Design: Retrospective observational study. Setting: Teaching hospitals in London UK, Nottingham UK and New York USA. Participants: Singleton pregnancies with no known fetal abnormality. Methods: Archived fetal ECG's performed using the MonicaAN24 monitor. A single ECG (PQRST) complex was generated from 5000 signal-averaged beats and electrical cardiac time intervals measured in an automated way and manually. Main Outcome measure: Validation of a newly developed algorithm to measure the cardiac time intervals of the fetal ECG. Results: 188/236 (79.7%) subjects with fECGs of suitable signal:noise ratio were included for analysis comparing manual with automated measurement. PR interval was measured in 173/188 (92%), QRS complex in 170/188 (90%) and QT interval in 123/188 (65.4%). PR interval was 107.6 (12.07) ms [mean(SD)] manual vs 109.11 (14.7) ms algorithm. QRS duration was 54.72(6.35) ms manual vs 58.34(5.73) ms algorithm. QT-interval was 268.93 (21.59) ms manual vs 261.63 (36.16) ms algorithm. QTc was 407.5(32.71) ms manual vs 396.4 (54.78) ms algorithm. The QRS-duration increased with gestational age in both manual and algorithm measurements. Conclusion: Accurate measurement of fetal ECG cardiac time intervals can be automated with potential application to interpretation of larger datasets.

Impact of prospective measurement of outflow tracts in prediction of coarctation of the aorta.

OBJECTIVES: Prenatal diagnosis of coarctation of the aorta (CoA) is associated with reduced mortality and morbidity, however, accurate prenatal prediction remains challenging. To date, studies have used retrospective measurements of the outflow tracts to evaluate their potential to predict CoA. Our primary objective was to evaluate prospectively acquired measurements of the outflow tracts in fetuses with prenatally suspected CoA. A secondary aim was to report the postnatal prevalence of bicuspid aortic valve in this cohort. METHODS: Pregnancies with suspicion of isolated CoA and with a minimum of 6 months' postnatal follow-up available were identified from the cardiac database of a tertiary fetal cardiology center in the UK, between January 2002 and December 2017. Measurement of the aortic valve, pulmonary valve, distal transverse aortic arch (DTAA) and arterial duct (AD) diameters were undertaken routinely in fetuses with suspected CoA during the study period. Z-scores were computed using published reference ranges based on > 7000 fetuses from our own unit. RESULTS: Of 149 pregnancies with prenatally suspected CoA included in the study, CoA was confirmed within 6 months after birth in 77/149 (51.7%) cases. DTAA diameter Z-score and the Z-score of second-trimester DTAA/AD diameter ratio were smaller in fetuses with postnatally confirmed CoA than those in false-positive cases (-2.8 vs -1.9; P = 0.039 and -3.13 vs -2.61; P = 0.005, respectively). Multiple regression analysis demonstrated that the Z-scores of DTAA and AD diameters were the only significant predictors of postnatal CoA (P = 0.001). Bicuspid aortic valve was identified in 30% of the false-positive cases. CONCLUSIONS: Measurement of DTAA and AD diameter Z-scores can be used to ascertain risk for postnatal CoA in a selected cohort. The high incidence of bicuspid aortic valve in false-positive cases merits further study with respect to both etiology and longer-term significance. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Post-glacial habitat release and incipient speciation in the genus Delphinus.

The role of ecological and changing environmental factors in the radiation of species diversity is a fundamental question in evolutionary biology. Of particular interest is the potential for these factors to determine the boundary between what we would consider differentiation among populations and incipient speciation. Dolphins in the genus Delphinus provide a useful test case, exhibiting morphological variation in beak length, coloration and body size across their wide geographic distribution, and in particular among coastal and more pelagic habitats. Two species have been proposed, D. delphis and D. capensis, but morphologically similar allopatric populations are not monophyletic, indicating that the mostly coastal 'long-beaked' D. capensis form is not a single globally distributed species. However, the sympatric populations in the Eastern North Pacific currently designated as these two species are both morphologically and genetically differentiated. Here we use microsatellite DNA and mitochondrial DNA markers to investigate the evolutionary mechanisms that led to this incipient speciation event. We used coalescent and assignment methods to investigate the timing and extent of reproductive isolation. Our data indicate that although there is some level of on-going gene flow, the putative species found in the Eastern North Pacific are reciprocally monophyletic. The timing of isolation appears to be associated with regional changes in paleoceanographic conditions within the Holocene timeframe.

Assessing the risk of ships striking large whales in marine spatial planning.

Marine spatial planning provides a comprehensive framework for managing multiple uses of the marine environment and has the potential to minimize environmental impacts and reduce conflicts among users. Spatially explicit assessments of the risks to key marine species from human activities are a requirement of marine spatial planning. We assessed the risk of ships striking humpback (Megaptera novaeangliae), blue (Balaenoptera musculus), and fin (Balaenoptera physalus) whales in alternative shipping routes derived from patterns of shipping traffic off Southern California (U.S.A.). Specifically, we developed whale-habitat models and assumed ship-strike risk for the alternative shipping routes was proportional to the number of whales predicted by the models to occur within each route. This definition of risk assumes all ships travel within a single route. We also calculated risk assuming ships travel via multiple routes. We estimated the potential for conflict between shipping and other uses (military training and fishing) due to overlap with the routes. We also estimated the overlap between shipping routes and protected areas. The route with the lowest risk for humpback whales had the highest risk for fin whales and vice versa. Risk to both species may be ameliorated by creating a new route south of the northern Channel Islands and spreading traffic between this new route and the existing route in the Santa Barbara Channel. Creating a longer route may reduce the overlap between shipping and other uses by concentrating shipping traffic. Blue whales are distributed more evenly across our study area than humpback and fin whales; thus, risk could not be ameliorated by concentrating shipping traffic in any of the routes we considered. Reducing ship-strike risk for blue whales may be necessary because our estimate of the potential number of strikes suggests that they are likely to exceed allowable levels of anthropogenic impacts established under U.S. laws.

Comparison of electrocardiographic analysis for risk of QT interval prolongation using safety pharmacology and toxicological studies.

Testing for possible cardiovascular side effects of new drugs has been an essential part of drug development for years. A more detailed analysis of the electrocardiogram (ECG) to detect effects on ventricular repolarization (effects on the QT interval), as a marker for possible proarrhythmic potential has been added to that evaluation in recent years. State-of-the art evaluation of drug-induced effects on the QT interval have evolved, but due to the complexity of the assessment, the trend in safety pharmacology studies has been to collect large numbers of high quality ECGs to allow for a robust assessment including the influence of heart rate on the QT interval apart from possible drug-induced effects. Since an assessment of the ECG is often included in toxicological studies, one can consider making such an assessment using ECG data from routine toxicological studies. This review summarizes various aspects of both safety pharmacology and toxicology studies with regards to their impact on the quality and quantity of ECG data that one can reasonably derive. We conclude that ECG data from toxicological studies can offer complementary ECG data that can strengthen a risk assessment. However, for the great majority of standard toxicity studies conducted, the ECG data collected do not permit an adequate assessment of drug-induced effects on the QT interval with the sensitivity expected from the ICH S7B guidelines. Furthermore, sponsors should be discouraged from performing any analyses on low quality ECGs to avoid generating misleading data. Substantial improvements in ECG quality and quantity are available, thereby making a QT interval assessment within the context of a standard toxicological study feasible, but these methods may require a larger commitment of resources from the sponsor. From the viewpoint of risk mitigation and limiting the attrition of promising new therapies, a commitment of resources to insure ECG data quality in either toxicology or safety pharmacology studies may be well justified.

Cartilage imaging in osteoarthritis.

Osteoarthritis (OA) is the most common articular disorder encountered worldwide. Its successful evaluation (and eventual treatment) depends on establishing a set of criteria for measuring disease progression. An ideal measurement would evaluate changes in articular cartilage, where the primary pathology of the disease takes place. Plain radiographs are the simplest and most readily employable means of joint evaluation, and now microfocal radiographs have been developed, which magnify the radiograph and help portray the joint space more accurately. However, radiography, along with nuclear medicine scans, arthrography, and computed tomography (CT) scans, are limited in their use because they are unable to detect early cartilage abnormalities. Magnetic resonance imaging (MRI) has the advantages of multiplanar imaging, soft tissue contrast, and noninvasiveness. Like radiography, MRI can underestimate the extent of cartilage abnormality. The most sensitive technique for measuring superficial articular abnormalities is arthroscopy, and small-bore arthroscopes are being used to assess knee damage in conscious, nonsedated patients. However, it is not yet clear if arthroscopy can detect subtle changes over time, and vision can be blocked by cloudy synovial fluid. Finally, although it is usually well tolerated, arthroscopy is an invasive technique.

Effects of early social experience on activity and object investigation in the ferret.

Earlier experiments have shown that many of the effects of early social isolation in the rat may be due to deprivation of social play. The isolated ferret, like the isolated rat, is hyperactive; furthermore, its hyperactivity appears to be related to deprivation of social play. However, the relationship between object investigation and social rearing is more complex in the ferret than it is in the rat.

Isolation has permanent effects upon the behavior of the rat, but not the mouse, gerbil, or guinea pig.

In the rat isolation has both short- and long-term influences upon behavior. Rats isolated at any age will show increases in timidity and aggression, but both effects can be reversed by periods of social housing. However, isolation before 50 days of age has permanent effects upon behavior. We have previously found that rats between 25 and 45 days of age may be protected from the deleterious effects of isolation by short daily periods of social contact if, during these daily contact periods, the rats engage in intense bouts of rough-and-tumble play. In this study we examined the permanence of the effects of isolation on the rat, mouse, guinea pig and gerbil. As predicted by the play hypothesis, species which do not engage in extensive social play do not show permanent deficits if isolated prior to 50 days. Only rats which engage in long bouts of rough-and-tumble play between 20 and 50 days show any permanent behavioral effects of isolation during this period.