Interaction between clinicians and artificial intelligence to detect fetal atrioventricular septal defects on ultrasound: how can we optimize collaborative performance?

OBJECTIVES: Artificial intelligence (AI) has shown promise in improving the performance of fetal ultrasound screening in detecting congenital heart disease (CHD). The effect of giving AI advice to human operators has not been studied in this context. Giving additional information about AI model workings, such as confidence scores for AI predictions, may be a way of further improving performance. Our aims were to investigate whether AI advice improved overall diagnostic accuracy (using a single CHD lesion as an exemplar), and to determine what, if any, additional information given to clinicians optimized the overall performance of the clinician-AI team. METHODS: An AI model was trained to classify a single fetal CHD lesion (atrioventricular septal defect (AVSD)), using a retrospective cohort of 121 130 cardiac four-chamber images extracted from 173 ultrasound scan videos (98 with normal hearts, 75 with AVSD); a ResNet50 model architecture was used. Temperature scaling of model prediction probability was performed on a validation set, and gradient-weighted class activation maps (grad-CAMs) produced. Ten clinicians (two consultant fetal cardiologists, three trainees in pediatric cardiology and five fetal cardiac sonographers) were recruited from a center of fetal cardiology to participate. Each participant was shown 2000 fetal four-chamber images in a random order (1000 normal and 1000 AVSD). The dataset comprised 500 images, each shown in four conditions: (1) image alone without AI output; (2) image with binary AI classification; (3) image with AI model confidence; and (4) image with grad-CAM image overlays. The clinicians were asked to classify each image as normal or AVSD. RESULTS: A total of 20 000 image classifications were recorded from 10 clinicians. The AI model alone achieved an accuracy of 0.798 (95% CI, 0.760-0.832), a sensitivity of 0.868 (95% CI, 0.834-0.902) and a specificity of 0.728 (95% CI, 0.702-0.754), and the clinicians without AI achieved an accuracy of 0.844 (95% CI, 0.834-0.854), a sensitivity of 0.827 (95% CI, 0.795-0.858) and a specificity of 0.861 (95% CI, 0.828-0.895). Showing a binary (normal or AVSD) AI model output resulted in significant improvement in accuracy to 0.865 (P < 0.001). This effect was seen in both experienced and less-experienced participants. Giving incorrect AI advice resulted in a significant deterioration in overall accuracy, from 0.761 to 0.693 (P < 0.001), which was driven by an increase in both Type-I and Type-II errors by the clinicians. This effect was worsened by showing model confidence (accuracy, 0.649; P < 0.001) or grad-CAM (accuracy, 0.644; P < 0.001). CONCLUSIONS: AI has the potential to improve performance when used in collaboration with clinicians, even if the model performance does not reach expert level. Giving additional information about model workings such as model confidence and class activation map image overlays did not improve overall performance, and actually worsened performance for images for which the AI model was incorrect. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Search for Lorentz invariance and CPT violation with the MINOS far detector.

We searched for a sidereal modulation in the MINOS far detector neutrino rate. Such a signal would be a consequence of Lorentz and CPT violation as described by the standard-model extension framework. It also would be the first detection of a perturbative effect to conventional neutrino mass oscillations. We found no evidence for this sidereal signature, and the upper limits placed on the magnitudes of the Lorentz and CPT violating coefficients describing the theory are an improvement by factors of 20-510 over the current best limits found by using the MINOS near detector.

UK: the current state of regulation of complementary and alternative medicine.

There is no legislation that restricts the practice of CAM in the UK apart from the practice of chiropractic and osteopathy and limits on advertising the treatments of certain conditions such as cancer and tuberculosis. The UK government has increasingly recognised the need for comprehensive regulation of CAM, though it abandoned its original plan for a single overarching regulatory body. Initiatives to examine and hasten the process of regulation have included setting up a central, well-recognised charitable body to facilitate progress for individual professions, and an authoritative survey of the existing professional organisations. One pathway open to individual professions is statutory self-regulation, which requires a single governing body, a systematic corpus of knowledge, recognised training courses and demonstrated efficacy. The other pathway is voluntary self-regulation. Chiropractic and osteopathy have adopted statutory self-regulation, though this has proved expensive for individual members of these professions. A recent House of Lords report on CAM has recommended that the herbal medicine and acupuncture professions should also develop a system of statutory regulation. Other professions, such as aromatherapy, are in the process of establishing single professional bodies as a first step towards self-regulation. Among the issues that remain to be resolved is the relationship between the CAM professions and statutory registered practitioners who also practise CAM.

The Poole Diabetes Study: how many cases of Type 2 diabetes are diagnosed each year during normal health care in a defined community?

UNLABELLED: We have investigated the incidence of newly diagnosed Type 2 diabetes in the Poole area and extrapolated it to the rest of the UK. METHODS: this prospective observational study used a surveillance programme in primary and secondary care. We identified all cases of newly diagnosed Type 2 diabetes mellitus occurring from 1st May 1996 to 30th June 1998 through the normal health care process without any active screening in 186889 people registered with 24 primary care practices in the Poole area. RESULTS: the 1996 prevalence of diagnosed Type 2 diabetes in this population was 1.59 (95% CI 1.53-1.65%)%. During the first 24 months of the study, 706 new cases of Type 2 diabetes mellitus, 382 men and 324 women, were identified. The crude annual incidence of newly diagnosed Type 2 diabetes, thus was 1.93/1000 (95% CI 1.73-2.13%) and age/sex adjusted incidence was 1.67/1000 (95% CI 1.49-1.84%). The age-adjusted incidence was higher in men, 1.86/1000 (95% CI 1.60-2.13), than in women, 1.48/1000 (95% CI 1.25-1.71%), relative risk 1.26 (95% CI 0.997-1.527%), but this difference did not reach statistical significance. Mean HbA1c at diagnosis was 10.8 (S.D. 2.9%)%. Men were younger at diagnosis than women (mean age, 62.9 vs. 65.9%, P<0.01). CONCLUSION: in UK, prior to the change in the WHO diagnostic criteria for diabetes, we estimate that over 98000 new cases of Type 2 diabetes were diagnosed each year.

Effect of immunization with recombinant OspA on serologic tests for Lyme borreliosis.

This study evaluated the effects of vaccination with OspA on the use of serologic tests as aids in the diagnosis of Lyme borreliosis. Sera from control and OspA-immunized mice and from OspA-immunized human volunteers were tested for serologic reactivity to Borrelia burgdorferi. Testing was performed with samples obtained prior to administration of vaccine and at 30 days following administration of an initial and a second dose of OspA vaccine. The assays used to assess serologic reactivity included an in-house-developed enzyme-linked immunosorbent assay (ELISA), an in-house-developed Western blot assay, two commercial Western blot tests, and a commercially available dot blot assay. Data obtained from this study demonstrate that immunization with the OspA vaccine will cause ELISA to yield positive results (as reported previously) for the majority of vaccine recipients. Results obtained from Western blot analysis indicate that vaccination with recombinant OspA induces production of antibodies which bind to several different borrelial proteins. The degree of reactivity detected by Western blotting varied greatly between the three assays used. The in-house assay showed the least reactivity, while one commercial Western blot test actually yielded positive test results for infection with B. burgdorferi. The usefulness of all three Western blot assays for the diagnosis of potential infection in a vaccine recipient is severely limited by the extensive reactivity caused by vaccination alone. Antibodies produced in response to OspA vaccination did not significantly affect the performance of the dot blot test; thus, it could provide a reliable means to test for infection with B. burgdorferi in OspA vaccine recipients.

Mitochondrial and extramitochondrial apoptotic signaling pathways in cerebrocortical neurons.

In cultured cerebrocortical neurons, mild excitotoxic insults or staurosporine result in apoptosis. We show here that N-methyl-d-aspartate (NMDA) receptor-mediated, but not staurosporine-mediated, apoptosis is preceded by depolarization of the mitochondrial membrane potential (Deltapsi(m)) and ATP loss. Both insults, however, release cytochrome c (Cyt c) into the cytoplasm. What prompts mitochondria to release Cyt c and the mechanism of release are as yet unknown. We examined the effect of inhibition of the adenine nucleotide translocator (ANT), a putative component of the mitochondrial permeability transition pore. Inhibition of the mitochondrial ANT with bongkrekic acid (BA) prevented NMDA receptor-mediated apoptosis of cerebrocortical neurons. Concomitantly, BA prevented Deltapsi(m) depolarization, promoted recovery of cellular ATP content, and blocked caspase-3 activation. However, in the presence of BA, Cyt c was still released. Because BA prevented NMDA-induced caspase-3 activation and apoptosis, the presence of Cyt c in the neuronal cytoplasm is not sufficient for the induction of caspase activity or apoptosis. In contrast to these findings, BA was ineffective in preventing staurosporine-induced activation of caspases or apoptosis. Additionally, staurosporine-induced, but not NMDA-induced, apoptosis was associated with activation of caspase-8. These results indicate that, in cerebrocortical cultures, excessive NMDA receptor activation precipitates neuronal apoptosis by means of mitochondrial dysfunction, whereas staurosporine utilizes a distinct pathway.

Mitochondria and neuronal survival.

Mitochondria play a central role in the survival and death of neurons. The detailed bioenergetic mechanisms by which isolated mitochondria generate ATP, sequester Ca(2+), generate reactive oxygen species, and undergo Ca(2+)-dependent permeabilization of their inner membrane are currently being applied to the function of mitochondria in situ within neurons under physiological and pathophysiological conditions. Here we review the functional bioenergetics of isolated mitochondria, with emphasis on the chemiosmotic proton circuit and the application (and occasional misapplication) of these principles to intact neurons. Mitochondria play an integral role in both necrotic and apoptotic neuronal cell death, and the bioenergetic principles underlying current studies are reviewed.

Moxibustion for breech presentation.

Breech presentation at term is considered a possible obstetric complication, and the management before and during labour remains controversial. A technique called 'moxibustion' is used in traditional Chinese medicine to encourage version of the fetus in breech presentation. It has been used in the maternity unit in Plymouth for 11 years. The results would seem to suggest it may have a positive effect and play a part in reducing the number of breech presentations at term and therefore also a reduction in the number of caesarean sections which are so often advocated in breech presentation. This article describes the technique in greater detail and discusses the potential for the future.

Excitotoxicity and mitochondria.

Excitotoxicity is the process whereby a massive glutamate release in the central nervous system in response to ischaemia or related trauma leads to the delayed, predominantly necrotic death of neurons. Excitotoxicity is also implicated in a variety of slow neurodegenerative disorders. Mitochondria accumulate much of the post-ischaemic calcium entering the neurons via the chronically activated N-methyl-D-aspartate receptor. This calcium accumulation plays a key role in the subsequent death of the neuron. Cultured cerebellar granule cells demonstrate delayed calcium de-regulation (DCD) followed by necrosis upon exposure to glutamate. DCD is unaffected by the ATP synthase inhibitor oligomycin but is inhibited by the further addition of a respiratory chain inhibitor to depolarize the mitochondria and inhibit mitochondrial calcium accumulation without depleting ATP [Budd and Nicholls (1996) J. Neurochem. 67, 2282-2291]. Mitochondrial depolarization paradoxically decreases the cytoplasmic calcium elevation following glutamate addition, probably due to an enhanced calcium efflux from the cell. Cells undergo immediate calcium de-regulation in the presence of glutamate if the respiratory chain is inhibited; this is due to ATP depletion following ATP synthase reversal and can be reversed by oligomycin. In contrast, DCD is irreversible. Elevated cytoplasmic calcium is not excitotoxic as long as mitochondria are depolarized; alternative substrates do not rescue cells about to undergo DCD, suggesting that glycolytic failure is not involved. Mitochondria in situ remain sufficiently polarized during granule cell glutamate exposure to continue to generate ATP and show a classic mitochondrial state 3-state 4 hyperpolarization on inhibiting ATP synthesis; mitochondrial depolarization follows, and may be a consequence of rather than a cause of DCD. In addition, our studies show no evidence of the mitochondrial permeability transition prior to DCD. The mitochondrial generation of superoxide anions is enhanced during glutamate exposure and a working hypothesis is that DCD may be caused by oxidative damage to calcium extrusion pathways at the plasma membrane.

Glutamate excitotoxicity and neuronal energy metabolism.

The bioenergetic properties of the in situ mitochondria play a central role in controlling the susceptibility of neurons to acute or chronic neurodegenerative stress. The mitochondrial membrane potential, delta psi m is the parameter that controls three interrelated mitochondrial functions of great relevance to neuronal survival: namely, ATP synthesis, Ca2+ accumulation, and superoxide generation. The in vitro model we study is the rat cerebellar granule cell in primary culture and its susceptibility to NMDA receptor-mediated necrosis, which is preceded by a delayed failure of cytoplasmic Ca2+ homeostasis ("delayed Ca2+ deregulation," DCD). DCD is not caused by a failure of mitochondrial ATP synthesis since it also occurs in cells maintained purely by glycolysis. The in situ mitochondria maintain a delta psi m sufficient for ATP synthesis throughout the exposure of the cells to glutamate until DCD occurs. Even at that stage it appears that mitochondrial depolarization may be an effect of DCD rather than a primary cause. This somewhat unorthodox view resolves a number of apparent paradoxes, such as observations of enhanced superoxide generation by in situ mitochondria during excitotoxic exposure, since isolated mitochondria generate superoxide only under conditions of high delta psi m. Mitochondrial depolarization by selective inhibitors that do not deplete cellular ATP is acutely neuroprotective.

Mechanisms of neuronal damage in brain hypoxia/ischemia: focus on the role of mitochondrial calcium accumulation.

Following a hypoxic-ischemic insult, the collapse of ion gradients results in the inappropriate release of excitatory neurotransmitters. Although excitatory amino acids such as glutamate are the likely extracellular mediators of the ensuing neuronal cell death, the intracellular events occurring downstream of glutamate receptor activation are much less clear. The present review attempts to summarize how Ca2+ overload of neurons following a hypoxic-ischemic insult is neurotoxic. In particular, the interlocked relation between mitochondrial Ca2+ accumulation and subsequent neuronal cell death is examined.

Mitochondrial control of acute glutamate excitotoxicity in cultured cerebellar granule cells.

Mitochondria within cultured rat cerebellar granule cells have a complex influence on cytoplasmic free Ca2+ ([Ca2+]c) responses to glutamate. A decreased initial [Ca2+]c elevation in cells whose mitochondria are depolarized by inhibition of the ATP synthase and respiratory chain (conditions which avoid ATP depletion) was attributed to enhanced Ca2+ extrusion from the cell rather than inhibited Ca2+ entry via the NMDA receptor. Even in the presence of elevated extracellular Ca2+, when [Ca2+]c responses were restored to control values, such cells showed resistance to acute excitotoxicity, defined as a delayed cytoplasmic Ca2+ deregulation (DCD) during glutamate exposure. DCD was a function of the duration of mitochondrial polarization in the presence of glutamate rather than the total period of glutamate exposure. Once initiated, DCD could not be reversed by NMDA receptor inhibition. In the absence of ATP synthase inhibition, respiratory chain inhibitors produced an immediate Ca2+ deregulation (ICD), ascribed to an ATP deficit. In contrast to DCD, ICD could be reversed by subsequent ATP synthase inhibition with or without additional NMDA receptor blockade. DCD could not be ascribed to the failure of an ATP yielding metabolic pathway. It is concluded that mitochondria can control Ca2+ extrusion from glutamate-exposed granule cells by the plasma membrane in three ways: by competing with efflux pathways for Ca2+, by restricting ATP supply, and by inducing a delayed failure of Ca2+ extrusion. Inhibitors of the mitochondrial permeability transition only marginally delayed the onset of DCD.

Grading and hemodynamic follow-up study of arteriovenous malformations with transcranial Doppler ultrasonography.

This study presents and tests the clinical validity of a hemodynamic grading system that depends on noninvasive transcranial Doppler ultrasonographic parameters. The suggested transcranial Doppler-based grading system was compared with the Spetzler-Martin anatomic grading for prognosticative validity and clinical dependability. We concluded the following: (1) The pulsatility index was shown to be a more dependable transcranial Doppler parameter in the clinical evaluation of an arteriovenous malformation because of two reasons: preoperative pulsatility index findings inversely correlated with arteriovenous malformation volume, and the pulsatility index returned to normal values before the mean blood flow velocity did. Therefore, hemodynamic arteriovenous malformation grading can be based on the pulsatility index. (2) A transcranial Doppler-based hemodynamic arteriovenous malformation grading system correlated highly with the Spetzler-Martin grading in predicting postoperative neurologic deficits and adverse radiologic findings. (3) The presented grading system may contribute to the standardization and quantification of the hemodynamic changes during multidisciplinary management of arteriovenous malformations.

Evidence of an increasing prevalence of diagnosed diabetes mellitus in the Poole area from 1983 to 1996.

This study examined the prevalence of diagnosed diabetes mellitus in a defined population over 13 years by undertaking cross-sectional surveys on 3 occasions between 1983 and 1996. The study population consisted of all the people registered with 10 general (primary care) practices at the time of each survey; 90660 in 1983/4; 97122 in 1988/9; and 86287 in 1996. Ascertainment of cases was by a surveillance programme in general practice and the hospital diabetes department. The number of diabetic patients increased significantly over the study period: in 1983/4, there were 917 patients, crude prevalence 1.01% (95% CI 0.95-1.08%); in 1988/9, 1150 patients, crude prevalence 1.17% (1.12-1.25%); and in 1996, 1604 patients, crude prevalence 1.86% (1.77-1.95%). The prevalence adjusted to the age and sex distribution of the UK was 0.97% (95% CI 0.90-1.03%) in 1983/4, 1.05% (0.99-1.11%) in 1988/9 and 1.55% (1.48-1.63%) in 1996. The main increase in prevalence was due to Type 2 diabetes mellitus, crude prevalence 0.75% (95% CI 0.69-0.81%) in 1983/4, 0.92% (0.86-0.98%) in 1988/9 and 1.52% (1.44-1.60%) in 1996 rather than Type 1 diabetes mellitus, crude prevalence 0.25% (0.21-0.28%) in 1983/4, 0.25% (0.22-0.28%) in 1988/9 and 0.34% (0.30-0.38%) in 1996. During the study period, the crude prevalence of diagnosed diabetes was significantly greater in men than women; in 1983/4 men 1.1% (95% CI 1.00-1.20%) versus women 0.93% (0.84-1.02%); in 1988/9, men 1.31% (1.21-1.41%) versus women 1.07% (0.98-1.16%); and in 1996, men 2.13% (2.00-2.27%) versus women 1.60% (1.49-1.72%). This difference was statistically significant in the 1988/9 and 1996 surveys. In conclusion, over 13 years there was a significant increase of 83.6% in the prevalence of diagnosed diabetes mellitus in the Poole area, with the UK age and sex adjusted prevalence increasing by 60.7%.

Marginal adaptation of implant-supported metal-ceramic crowns fabricated with gold cylinders.

PURPOSE: The purpose of this investigation was to determine the mean marginal discrepancy of metal-ceramic crowns fabricated with gold cylinders and cemented on implant abutments. These discrepancies were then compared with those measured previously for implant-supported ceramic crowns. MATERIALS AND METHODS: Fifteen Nobel BioCare CeraOne abutments were connected to implant fixtures embedded in acrylic resin blocks. Marginal discrepancies were determined for gold cylinders, gold cylinders plus ceramic alloy (metal frameworks), completed metal-ceramic crowns, and cemented metal-ceramic crowns using a stereomicroscope equipped with a video camera linked to a computer. A Hotelling's T2 test (p < or = .05) was used to evaluate potential differences in mean marginal discrepancies among groups. RESULTS: The mean marginal discrepancies were: 1) gold cylinders, 7.56 +/- 2.73 microns; 2) metal frameworks, 6.21 +/- 1.34 microns; 3) metal-ceramic crowns, 11.06 +/- 3.21 microns; and 4) zinc-phosphate cemented crowns, 31.47 +/- 6.65 microns. No significant difference between gold cylinders and metal frameworks was found. Mean marginal discrepancies for metal-ceramic crowns were significantly greater than discrepancies for cast gold cylinders. Cemented-crown mean marginal discrepancy was significantly greater than all other means. CONCLUSIONS: Cemented metal-ceramic crowns fabricated using proprietary gold cylinders exhibited well-fitting margins (31.47 microns).

Mitochondria and neuronal glutamate excitotoxicity.

The role of mitochondria in the control of glutamate excitotoxicity is investigated. The response of cultured cerebellar granule cells to continuous glutamate exposure is characterised by a transient elevation in cytoplasmic free calcium concentration followed by decay to a plateau as NMDA receptors partially inactivate. After a variable latent period, a secondary, irreversible increase in calcium occurs (delayed calcium deregulation, DCD) which precedes and predicts subsequent cell death. DCD is not controlled by mitochondrial ATP synthesis since it is unchanged in the presence of the ATP synthase inhibitor oligomycin in cells with active glycolysis. However, mitochondrial depolarisation (and hence inhibition of mitochondrial calcium accumulation) without parallel ATP depletion (oligomycin plus either rotenone or antimycin A) strongly protects the cells against DCD. Glutamate exposure is associated with an increase in the generation of superoxide anion by the cells, but superoxide generation in the absence of mitochondrial calcium accumulation is not neurotoxic. While it is concluded that mitochondrial calcium accumulation plays a critical role in the induction of DCD we can find no evidence for the involvement of the mitochondrial permeability transition.