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.

Demonstration of Scale-Invariant Rayleigh-Taylor Instability Growth in Laser-Driven Cylindrical Implosion Experiments.

Rayleigh-Taylor instability growth is shown to be hydrodynamically scale invariant in convergent cylindrical implosions for targets that varied in radial dimension and implosion timescale by a factor of 3. The targets were driven directly by laser irradiation providing a short impulse, and instability growth at an embedded aluminum interface occurs as it converges radially inward by a factor of 2.25 and decelerates on a central foam core. Late-time growth factors of 14 are observed for a single-mode m=20 azimuthal perturbation at both scales, despite the differences in laser drive conditions between the experimental facilities, consistent with predictions from radiation-hydrodynamics simulations. This platform enables detailed investigations into the limits of hydrodynamic scaling in high-energy-density systems.

Increased uptake and improved outcomes of bowel cancer screening with a faecal immunochemical test: results from a pilot study within the national screening programme in England.

BACKGROUND: The National Health Service Bowel Cancer Screening Programme (BCSP) in England uses a guaiac-based faecal occult blood test (gFOBt). A quantitative faecal immunochemical test (FIT) for haemoglobin (Hb) has many advantages, including being specific for human blood, detecting Hb at a much lower concentration with a single faecal sample and improved uptake. METHODS: In 2014, a large comparative pilot study was performed within BCSP to establish the acceptability and diagnostic performance of FIT. Over a 6-month period, 40 930 (1 in 28) subjects were sent a FIT (OC-SENSOR) instead of a gFOBt. A bespoke FIT package was used to mail FIT sampling devices to and from FIT subjects. All participants positive with either gFOBt or FIT (cut-off 20 µg Hb/g faeces) were referred for follow-up. Subgroup analysis included cut-off concentrations, age, sex, screening history and deprivation quintile. RESULTS: While overall uptake increased by over 7 percentage points with FIT (66.4% vs 59.3%, OR 1.35, 95% CI 1.33 to 1.38), uptake by previous non-responders almost doubled (FIT 23.9% vs gFOBt 12.5%, OR 2.20, 95% CI 2.10 to 2.29). The increase in overall uptake was significantly higher in men than women and was observed across all deprivation quintiles. With the conventional 20 µg/g cut-off, FIT positivity was 7.8% and ranged from 5.7% in 59-64-year-old women to 11.1% in 70-75-year-old men. Cancer detection increased twofold and that for advanced adenomas nearly fivefold. Detection rates remained higher with FIT for advanced adenomas, even at 180 µg Hb/g. CONCLUSIONS: Markedly improved participation rates were achieved in a mature gFOBt-based national screening programme and disparities between men and women were reduced. High positivity rates, particularly in men and previous non-respondents, challenge the available colonoscopy resource, but improvements in neoplasia detection are still achievable within this limited resource.

Evaluating New Skill Sets for Performance Improvement: Human Factors as a Case Study.

New skill sets and improvement disciplines are constantly arising across the vast industrial and academic landscape of modern economies. Prescient hospital administrators are routinely searching for new and innovative ways to improve care, care delivery, safety, quality, and access. But, it can be challenging to identify those emerging skill sets, which will likely have lasting effect and will provide strong return on investment, from passing fads with little capacity to move performance benchmarks for a hospital. Here, we present a rubric for investigating new skill sets, using The Children's Hospital of Philadelphia's investigation into human factors engineering as a case study, and determining whether they can support hospital operations and improvements while providing sufficient return to justify the expense and challenge of incorporating ideas and methods into a quality and performance improvement environment.

Managing Disruptions to Patient Flow Capacity: Rapid-Cycle Improvement in a Pediatric Cardiac Procedure Complex.

BACKGROUND: Managing service disruptions is a challenge in every health care environment. Discrete event simulation (DES)--a computer modeling tool used to build in silico (that is, in a digital computer) testbeds for potential changes in complex systems--has been deployed in health care for research and quality improvement (QI), specifically in surgical suite management. A strategy for managing a 6-week planned service disruption needed to be enacted 12 weeks after the announcement, in late October 2014, of the closure of the Hybrid Suite (operating room/catheterization laboratory) for renovation, at The Children's Hospital of Philadelphia's Cardiac Center's Cardiac Operative and Imaging Complex (COIC). METHODS: A previously developed DES was queried to determine theoretical system throughput capacity during the temporary disruption. On the basis of this analysis, a rapid improvement event (RIE) was enacted to address systemic challenges to meeting demand with diminished capacity. During the RIE, system stakeholders (physicians, nurses, and technicians) engaged with performance improvement personnel to identify potential improvements, test those changes in rapid succession, and then implement successful candidates for the disruption. RESULTS: First-case start time was 43 minutes earlier during the period of diminished capacity. Turnaround time between cases was reduced by 23 minutes. Length of day increased by 1 hour, in accordance with simulated predictions. System throughput was 138 patients during the disruption, compared with 135 patients during the same period the previous year. CONCLUSION: A combination of systems analysis and QI methodologies enabled the Cardiac Center to meet demand during a six-week period of diminished capacity. Planned, temporary service disruptions, which must be managed by clinical personnel, can be addressed proactively with promising results.

Influence of high altitude on cerebral blood flow and fuel utilization during exercise and recovery.

We examined the hypotheses that: (1) during incremental exercise and recovery following 4-6 days at high altitude (HA) global cerebral blood flow (gCBF) increases to preserve cerebral oxygen delivery (CDO2) in excess of that required by an increasing cerebral metabolic rate of oxygen ( CM RO2); (2) the trans-cerebral exchange of oxygen vs. carbohydrates (OCI; carbohydrates = glucose + ½lactate) would be similar during exercise and recovery at HA and sea level (SL). Global CBF, intra-cranial arterial blood velocities, extra-cranial blood flows, and arterial-jugular venous substrate differences were measured during progressive steady-state exercise (20, 40, 60, 80, 100% maximum workload (Wmax)) and through 30 min of recovery. Measurements (n = 8) were made at SL and following partial acclimatization to 5050 m. At HA, absolute Wmax was reduced by ∼50%. During submaximal exercise workloads (20-60% Wmax), despite an elevated absolute gCBF (∼20%, P < 0.05) the relative increases in gCBF were not different at HA and SL. In contrast, gCBF was elevated at HA compared with SL during 80 and 100% Wmax and recovery. Notwithstanding a maintained CDO2 and elevated absolute CM RO2 at HA compared with SL, the relative increase in CM RO2 was similar during 20-80% Wmax but half that of the SL response (i.e. 17 vs. 27%; P < 0.05 vs. SL) at 100% Wmax. The OCI was reduced at HA compared with SL during 20, 40, and 60% Wmax but comparable at 80 and 100% Wmax. At HA, OCI returned almost immediately to baseline values during recovery, whereas at SL it remained below baseline. In conclusion, the elevations in gCBF during exercise and recovery at HA serve to maintain CDO2. Despite adequate CDO2 at HA the brain appears to increase non-oxidative metabolism during exercise and recovery.

Assessment of an anti-alpha-toxin monoclonal antibody for prevention and treatment of Staphylococcus aureus-induced pneumonia.

Alpha-toxin (AT) is a major virulence factor in the disease pathogenesis of Staphylococcus aureus. We previously identified a monoclonal antibody (MAb) against AT that reduced disease severity in a mouse dermonecrosis model. Here, we evaluate the activity of an affinity-optimized variant, LC10, in a mouse model of S. aureus pneumonia. Passive immunization with LC10 increased survival and reduced bacterial numbers in the lungs and kidneys of infected mice and showed protection against diverse S. aureus clinical isolates. The lungs of S. aureus-infected mice exhibited bacterial pneumonia, including widespread inflammation, whereas the lungs of mice that received LC10 exhibited minimal inflammation and retained healthy architecture. Consistent with reduced immune cell infiltration, LC10-treated animals had significantly lower (P < 0.05) proinflammatory cytokine and chemokine levels in the bronchoalveolar lavage fluid than did those of the control animals. This reduction in inflammation and damage to the LC10-treated animals resulted in reduced vascular protein leakage and CO2 levels in the blood. LC10 was also assessed for its therapeutic activity in combination with vancomycin or linezolid. Treatment with a combination of LC10 and vancomycin or linezolid resulted in a significant increase (P < 0.05) in survival relative to the monotherapies and was deemed additive to synergistic by isobologram analysis. Consistent with improved survival, the lungs of animals treated with antibiotic plus LC10 exhibited less inflammatory tissue damage than those that received monotherapy. These data provide insight into the mechanisms of protection provided by AT inhibition and support AT as a promising target for immunoprophylaxis or adjunctive therapy against S. aureus pneumonia.

Four-wave mixing and octave-spanning supercontinuum generation in a small core hydrogenated amorphous silicon fiber pumped in the mid-infrared.

An octave-spanning supercontinuum is generated in a hydrogenated amorphous silicon core fiber when pumped in the mid-infrared regime. The broadband wavelength conversion which extends from the edge of the telecommunications band into the mid-infrared (1.64-3.37 µm) is generated by four-wave mixing (FWM) and subsequent pulse break-up, facilitated by the high material nonlinear figure of merit and the anomalous dispersion of the relatively small 1.7 µm diameter core fiber. The FWM sidebands and corresponding supercontinuum can be tuned through the pump parameters, and show good agreement with the predicted phase-matching curves for the fiber.

Coinfection and the evolution of drug resistance.

Recent experimental work in the rodent malaria model has shown that when two or more strains share a host, there is competitive release of drug-resistant strains upon treatment. In other words, the propagule output of a particular strain is repressed when competing with other strains and increases upon the removal of this competition. This within-host effect is predicted to have an important impact on the evolution and growth of resistant strains. However, how this effect translates to epidemiological parameters at the between-host level, the level at which disease and resistance spread, has yet to be determined. Here we present a general, between-host epidemiological model that explicitly takes into account the effect of coinfection and competitive release. Although our model does show that when there is coinfection competitive release may contribute to the emergence of resistance, it also highlights an additional between-host effect. It is the combination of these two effects, the between-host effect and the within-host effect, that determines the overall influence of coinfection on the emergence of resistance. Therefore, even when competitive release of drug-resistant strains occurs, within an infected individual, it is not necessarily true that coinfection will result in the increased emergence of resistance. These results have important implications for the control of the emergence and spread of drug resistance.

Randomized in vivo trial evaluating plaque inhibition benefits of an advanced stannous-containing sodium fluoride dentifrice used in conjunction with power brush technology.

OBJECTIVE: To compare the plaque inhibition efficacy of a novel stannous-containing sodium fluoride test dentifrice to a standard anticavity negative control dentifrice, when both were used in conjunction with an advanced oscillating-rotating (O/R) power toothbrush. METHODS: This was a randomized, two-treatment, three-period, double-blind crossover study conducted in a population using an O/R power brush. Subjects brushed twice per day with their assigned dentifrice during the three-treatment periods, each lasting for 17 consecutive days. Each period was separated by a 4-day washout period during which subjects continued to use their O/R power toothbrush. Plaque levels were assessed and averaged amongst three assessments taken on days 15, 16 and 17 at the end of each treatment period using digital plaque imaging analysis. Assessments were carried out on the facial anterior tooth surfaces in the morning before brushing (A.M. prebrush) following whole-mouth brushing (30 s per quadrant) with the assigned dentifrice (A.M. post-brush) and in the afternoon (P.M.). RESULTS: Twenty-seven subjects were randomized and completed the study. During the 17-day usage period, the stannous-containing test NaF dentifrice demonstrated a statistically significant lower mean plaque area versus the negative control dentifrice at each assessment timepoint; overnight A.M. prebrush was 33.8% lower (P < 0.0001), A.M. post-brush was 21.8% lower (P < 0.01), and P.M. was 29.2% lower (P < 0.0001). CONCLUSION: A population of O/R power toothbrush users had significantly less plaque coverage for all three measurements when using a stannous-containing NaF dentifrice than when using a negative control (fluoride) dentifrice.

Nonlinear transmission properties of hydrogenated amorphous silicon core fibers towards the mid-infrared regime.

The nonlinear transmission properties of hydrogenated amorphous silicon (a-Si:H) core fibers are characterized from the near-infrared up to the edge of the mid-infrared regime. The results show that this material exhibits linear losses on the order of a few dB/cm, or less, over the entire wavelength range, decreasing down to a value of 0.29 dB/cm at 2.7µm, and negligible nonlinear losses beyond the two-photon absorption (TPA) edge ~ 1.7µm. By measuring the dispersion of the nonlinear Kerr and TPA parameters we have found that the nonlinear figure of merit (FOM(NL)) increases dramatically over this region, with FOM(NL) > 20 around 2µm and above. This characterization demonstrates the potential for a-Si:H fibers and waveguides to find use in nonlinear applications extending beyond telecoms and into the mid-infrared regime.

Nongenetic inheritance and the evolution of costly female preference.

In species where males provide neither direct benefits nor paternal care, it is typically assumed that female preferences are maintained by indirect selection reflecting genetic benefits to offspring of preferred males. However, it remains unclear whether populations harbour sufficient genetic variation in fitness to support costly female preferences - a problem called the 'lek paradox'. Here, we ask whether indirect selection on female preferences can be maintained by nongenetic inheritance. We construct a general model that can be used to represent either genetic or nongenetic inheritance, depending on the choice of parameter values. Interestingly, we find that costly preference is most likely to evolve and persist when fitness depends on an environmentally induced factor that can be transmitted over a single generation only, such as an environment-dependent paternal effect. Costly preference can also be supported when fitness depends on a highly mutable factor that can persist over multiple generations, such as an epigenetic mark, but the necessary conditions are more restrictive. Our findings show that nongenetic inheritance provides a plausible hypothesis for the maintenance of costly female preferences in species where males provide no direct benefits to females. Nongenetic paternal inheritance of fitness can occur in species lacking conventional forms of paternal care. Indeed, transmission of paternal condition via sperm-borne nongenetic factors may be more likely to evolve than conventional forms of paternal investment because sperm-borne effects are protected from cuckoldry. Our results furnish a novel example of an interaction between genetic and nongenetic inheritance that can lead to otherwise unexpected evolutionary outcomes.

Evidence that microglia mediate the neurobiological effects of chronic psychological stress on the medial prefrontal cortex.

Psychological stress contributes to the development of clinical depression. This has prompted many preclinical studies to investigate the neurobiology of this relationship, however, the effects of stress on glia remain unclear. In this study, we wished to determine, first, how exposure to chronic psychological stress affects microglial activity within the prefrontal cortex (PFC) and, second, whether the observed changes were meaningfully related to corresponding changes in local neuronal activity and PFC-regulated behavior. Therefore, we examined markers of microglial activation, antigen presentation, apoptosis, and persistent neuronal activation within the PFC after exposure to repeated restraint stress. We also examined the effect of stress on spatial working memory, a PFC-dependent function. Finally, we tested the ability of a microglial activation inhibitor (minocycline) to alter the impact of chronic stress on all of these endpoints. Stressor exposure produced positively correlated increases in microglial and long-term neuronal activation in the PFC but not antigen presentation or apoptosis. As expected, it also impaired spatial working memory. Importantly, minocycline reduced the impact of stress on neuronal activation and working memory, as well as microglial activation. These results suggest a role for microglia in mediating the effects of stress on PFC neuronal function and PFC-regulated behavior.

In vitro comparison of stannous fluoride, sodium fluoride, and sodium monofluorophosphate dentifrices in the prevention of enamel erosion.

OBJECTIVE: To compare the relative performance of commercially available dentifrices containing different types of fluoride to reduce enamel erosion from citric acid. METHODS: Two randomized parallel-group experiments were conducted, each with 48 bovine enamel samples randomly divided into six treatment legs. Each treatment leg went through 24 toothpaste treatment cycles, acid challenge (0.05M citric acid), and remineralization in artificial saliva. Total acid immersion after all cycles was 300 minutes for each test product; two test products in Experiment 1 were also evaluated for 180 minutes for comparison. Samples were analyzed blinded to treatment group for enamel loss by contact profilometry. One stabilized stannous fluoride (SnF2) dentifrice was compared to three sodium fluoride (NaF) dentifrices, two sodium monofluorophosphate (MFP) dentifrices, and one MFP plus calcium sodium phosphosilicate (CSP) dentifrice. All fluoride levels were 1450 ppm. A water control was also included. RESULTS: The dentifrice containing stabilized SnF2 was significantly (p < 0.0001) better at preventing enamel erosion compared to the NaF and MFP dentifrices. The SnF, dentifrice provided a 61.7% (p < 0.0001) reduction in enamel loss versus the water control. The comparable figures for NaF and MFP dentifrices were 36-39% (p < 0.0001) and 33% (p < 0.0001) reductions, respectively, compared to the water control. The MFP+CSP dentifrice was significantly (p < 0.05) less effective, providing a 23.2% (p = 0.0007) reduction versus the water control. CONCLUSION: Of the dentifrices included in this research, the stabilized SnF, dentifrice was the most effective at reducing enamel erosion from citric acid.

Regional brain blood flow in man during acute changes in arterial blood gases.

Despite the importance of blood flow on brainstem control of respiratory and autonomic function, little is known about regional cerebral blood flow (CBF) during changes in arterial blood gases.We quantified: (1) anterior and posterior CBF and reactivity through a wide range of steady-state changes in the partial pressures of CO2 (PaCO2) and O2 (PaO2) in arterial blood, and (2) determined if the internal carotid artery (ICA) and vertebral artery (VA) change diameter through the same range.We used near-concurrent vascular ultrasound measures of flow through the ICA and VA, and blood velocity in their downstream arteries (the middle (MCA) and posterior (PCA) cerebral arteries). Part A (n =16) examined iso-oxic changes in PaCO2, consisting of three hypocapnic stages (PaCO2 =∼15, ∼20 and ∼30 mmHg) and four hypercapnic stages (PaCO2 =∼50, ∼55, ∼60 and ∼65 mmHg). In Part B (n =10), during isocapnia, PaO2 was decreased to ∼60, ∼44, and ∼35 mmHg and increased to ∼320 mmHg and ∼430 mmHg. Stages lasted ∼15 min. Intra-arterial pressure was measured continuously; arterial blood gases were sampled at the end of each stage. There were three principal findings. (1) Regional reactivity: the VA reactivity to hypocapnia was larger than the ICA, MCA and PCA; hypercapnic reactivity was similar.With profound hypoxia (35 mmHg) the relative increase in VA flow was 50% greater than the other vessels. (2) Neck vessel diameters: changes in diameter (∼25%) of the ICA was positively related to changes in PaCO2 (R2, 0.63±0.26; P<0.05); VA diameter was unaltered in response to changed PaCO2 but yielded a diameter increase of +9% with severe hypoxia. (3) Intra- vs. extra-cerebral measures: MCA and PCA blood velocities yielded smaller reactivities and estimates of flow than VA and ICA flow. The findings respectively indicate: (1) disparate blood flow regulation to the brainstem and cortex; (2) cerebrovascular resistance is not solely modulated at the level of the arteriolar pial vessels; and (3) transcranial Doppler ultrasound may underestimate measurements of CBF during extreme hypoxia and/or hypercapnia.

Ultrafast wavelength conversion via cross-phase modulation in hydrogenated amorphous silicon optical fibers.

We present a characterization of the spectral modulation and wavelength shifting induced via cross-phase modulation (XPM) in a hydrogenated amorphous silicon (a-Si:H) core optical fiber. Pump-probe experiments using picosecond and femtosecond signal pulses are shown to be in good agreement with numerical simulations of the coupled nonlinear propagation equations. The large 10nm red-shifts obtained with the femtosecond probe pulses are attributed to the high Kerr nonlinearity of the a-Si:H material. Extinction ratios as high as 12 dB are measured for the conversion process at telecommunications wavelengths, indicating the potential for high-speed nonlinear optical control in a-Si:H fibers and waveguides.

Randomized digital plaque imaging trial evaluating plaque inhibition efficacy of a novel stabilized stannous fluoride dentifrice compared with an amine fluoride/stannous fluoride dentifrice.

OBJECTIVE: To assess the plaque inhibition efficacy ofa novel 0.454% stabilized stannous fluoride test dentifrice (SnF2) to an amine fluoride/stannous fluoride marketed control dentifrice (AmF/SnF2) using digital plaque imaging analysis (DPIA). METHODS: The 10-week study was a randomized, two-treatment, three-period, double-blind crossover design. Subjects brushed twice daily with their assigned dentifrice (SnF2 or AmF/SnF2) using a standard manual toothbrush during three treatment periods each lasting 17 days, separated by four-day washout periods. DPIA was used to analyze plaque coverage on facial surfaces of the 12 anterior teeth (canine to canine) by three assessments on Days 15, 16, and 17 at the end of each treatment period. Assessments were conducted the morning following no overnight brushing of facial surfaces (A.M. pre-brush), after 40 seconds of full mouth brushing with the assigned dentifrice (A.M. post-brush), and during the afternoon (P.M.). RESULTS: Twenty-seven subjects were randomized and completed the study. At each assessment time point, plaque levels for the SnF2 dentifrice were statistically significantly lower compared to those for the AmF/SnF2 dentifrice (21.4%, 22.6%, 24.3%, respectively; p < 0.0001 for all). CONCLUSION: Plaque coverage, as assessed by DPIA, was significantly lower with a novel SnF2 dentifrice than with the AmF/SnF2 dentifrice. The plaque control benefits of the SnF2 dentifrice seen at the morning and afternoon time points indicated significantly better inhibition of plaque re-growth.