Development of a chest X-ray machine learning convolutional neural network model on a budget and using artificial intelligence explainability techniques to analyze patterns of machine learning inference.

Objective: Machine learning (ML) will have a large impact on medicine and accessibility is important. This study's model was used to explore various concepts including how varying features of a model impacted behavior. Materials and Methods: This study built an ML model that classified chest X-rays as normal or abnormal by using ResNet50 as a base with transfer learning. A contrast enhancement mechanism was implemented to improve performance. After training with a dataset of publicly available chest radiographs, performance metrics were determined with a test set. The ResNet50 base was substituted with deeper architectures (ResNet101/152) and visualization methods used to help determine patterns of inference. Results: Performance metrics were an accuracy of 79%, recall 69%, precision 96%, and area under the curve of 0.9023. Accuracy improved to 82% and recall to 74% with contrast enhancement. When visualization methods were applied and the ratio of pixels used for inference measured, deeper architectures resulted in the model using larger portions of the image for inference as compared to ResNet50. Discussion: The model performed on par with many existing models despite consumer-grade hardware and smaller datasets. Individual models vary thus a single model's explainability may not be generalizable. Therefore, this study varied architecture and studied patterns of inference. With deeper ResNet architectures, the machine used larger portions of the image to make decisions. Conclusion: An example using a custom model showed that AI (Artificial Intelligence) can be accessible on consumer-grade hardware, and it also demonstrated an example of studying themes of ML explainability by varying ResNet architectures.

The role of loneliness in the association between sexual orientation and depressive symptoms among older adults: A prospective cohort study.

BACKGROUND: This study aims to understand the mechanisms contributing to the elevated risk of depression among sexual minority older adults compared to heterosexuals. Specifically, the role of loneliness as a potential mediator is investigated to inform targeted interventions for preventing depression in sexual minority populations. METHODS: Data from the English Longitudinal Study of Ageing, focusing on adults aged over 50, were analysed. Sexual orientation (sexual minority or heterosexual) and loneliness scores (UCLA scale) were assessed at wave six (2010-2011), while depressive symptoms (CESD) were assessed at wave seven (2013-14). Linear regression models and mediation analyses, using g-computation formula and adjusted for confounders, were conducted. RESULTS: The sample included 6794 participants, with 478 (7.0 %) identifying as sexual minorities. After adjustments, sexual minorities scored higher on depressive symptoms at wave seven (mean difference): 0.23, 95 % CI 0.07 to 0.39) and loneliness at wave six (MD: 0.27, 95 % CI 0.08 to 0.46). Loneliness was positively associated with depressive symptoms (coefficient: 0.27, 95 % CI 0.26 to 0.29). In mediation analyses, loneliness explained 15 % of the association between sexual orientation and subsequent depressive symptoms. LIMITATIONS: The dataset used sexual behaviour rather than desire and identity, potentially skewing representation of sexual minorities. Additionally, transgender older adults were not included due to limited gender diversity reported within the ELSA dataset. CONCLUSIONS: Loneliness appears to be a significant modifiable mechanism contributing to the heightened risk of depressive symptoms in sexual minority older adults compared with their heterosexual counterparts.

Unraveling Temporal Dynamics of Multidimensional Statistical Learning in Implicit and Explicit Systems: An X-Way Hypothesis.

Statistical learning enables humans to involuntarily process and utilize different kinds of patterns from the environment. However, the cognitive mechanisms underlying the simultaneous acquisition of multiple regularities from different perceptual modalities remain unclear. A novel multidimensional serial reaction time task was developed to test 40 participants' ability to learn simple first-order and complex second-order relations between uni-modal visual and cross-modal audio-visual stimuli. Using the difference in reaction times between sequenced and random stimuli as the index of domain-general statistical learning, a significant difference and dissociation of learning occurred between the initial and final learning phases. Furthermore, we used a negative and positive occurrence-frequency-and-reaction-time correlation to indicate implicit and explicit learning, respectively, and found that learning simple uni-modal patterns involved an implicit-to-explicit segue, while acquiring complex cross-modal patterns required an explicit-to-implicit segue, resulting in a X-shape crossing of regularity learning. Thus, we propose an X-way hypothesis to elucidate the dynamic interplay between the implicit and explicit systems at two distinct stages when acquiring various regularities in a multidimensional probability space.

Acute death as a result of poisoning tropical (Bos taurus indicus) but not temperate (Bos taurus taurus) cattle after oral dosing with Lupinus leucophyllus (velvet lupine).

Due to climate change and increasing summer temperatures, tropical cattle may graze where temperate cattle have grazed, exposing tropical cattle to toxic plants they may be unfamiliar with. This work compared the toxicity of Lupinus leucophyllus (velvet lupine) in temperate and tropical cattle. Orally dosed velvet lupine in tropical cattle caused death. If producers opt to graze tropical cattle, additional care must be taken on rangelands where toxic lupines like velvet lupine grow.

Effect of the Presence of Emergency Departments with 300 or More Hospital Beds in Health Service Areas on 30-Day Mortality in Korea: A Nationwide Retrospective Cross-sectional Study.

BACKGROUND: Disparities in emergency care accessibility exist between health service areas (HSAs). There is limited evidence on whether the presence of an emergency department (ED) that exceeds a certain hospital bed capacity is associated with emergency patient outcomes at the regional level. The objective of this study was to evaluate the effect of HSAs with or without of regional or local emergency centers with 300 or more hospital beds (EC300 or nEC300, respectively) by comparing the 30-day mortality of patients with severe emergency diseases (SEDs) admitted to the hospital through the ED. METHODS: The study retrospectively evaluated data from the Korean National Health Insurance Claims database and enrolled patients who were admitted from the ED for SEDs. SEDs were defined using ICD-10 codes for 28 disease categories with high severity, and 56 HSAs were designated as published by the Korean National Health Insurance Service. We performed hierarchical logistic regression analysis using multilevel models with the generalized linear mixed model (GLIMMIX) procedure to evaluate whether EC300 was associated with the 30-day mortality of SED patients, adjusting for patient-level, prehospital-level, hospital-level, and HSA-level variables. RESULTS: In total, 662,478 patients were analyzed, of whom 54,839 (8.3%) died within 30 days after hospital discharge. Of the 56 HSAs, 46 (82.1%) were included in the EC300 group. After adjustment for patient-level, prehospital-level, hospital-level and HSA-level variables, nEC300 was significantly associated with increased 30-day mortality in SED patients (AOR: 1.33, 95% CI: 1.137-1.153). In addition, patients who visited EDs with fewer annual SED admissions were associated with higher 30-day mortality. CONCLUSION: nEC300 had a greater risk of 30-day mortality in patients treated with SEDs than EC300. The results indicate that not only the number of EDs in each HSA is important for ensuring adequate patient outcomes but also the presence of EDs with adequate receiving capacity.

Consequences of pollen defense compounds for pollinators and antagonists in a pollen-rewarding plant.

Plants produce an array of defensive compounds with toxic or deterrent effects on insect herbivores. Pollen can contain relatively high concentrations of such defense compounds, but the causes and consequences of this enigmatic phenomenon remain mostly unknown. These compounds could potentially protect pollen against antagonists but could also reduce flower attractiveness to pollinators. We combined field observations of the pollen-rewarding Lupinus argenteus with chemical analysis and laboratory assays to test three hypotheses for the presence of pollen defense compounds: (1) these compounds are the result of spillover from adjacent tissues, (2) they protect against pollen thieves, and (3) they act as antimicrobial compounds. We also tested whether pollen defense compounds affect pollinator behavior. We found a positive relationship between alkaloid concentrations in pollen and petals, supporting the idea that pollen defense compounds partly originate from spillover. However, pollen and petals exhibited quantitatively (but not qualitatively) distinct alkaloid profiles, suggesting that plants can adjust pollen alkaloid composition independently from that of adjacent tissues. We found no relationship between pollen alkaloid concentration and the abundance of pollen thieves in Lupinus flowers. However, pollen alkaloids were negatively associated with bacterial abundance. Finally, plants with more alkaloids in their pollen received more pollinator visits, but these visits were shorter, resulting in no change in the overall number of flowers visited. We propose that pollen defense compounds are partly the result of spillover from other tissues, while they also play an antimicrobial role. The absence of negative effects of these compounds on pollinator visitation likely allows their maintenance in pollen at relatively high concentrations. Taken together, our results suggest that pollen alkaloids affect and are mediated by the interplay of multiple interactions.

Heat stress from current and predicted increases in temperature impairs lambing rates and birth weights in the Australian sheep flock.

Livestock heat stress threatens production, particularly in semi-arid, arid and tropical regions. Using established temperature thresholds for sheep, we modelled +1 °C and +3 °C temperature increases over the historical baseline, estimating that 2.1 million potential lambs are lost annually due to heat stress alone, increasing to 2.5 and 3.3 million, respectively, as temperatures rise. Heat stress poses risks at key periods of the reproductive cycle, with consequences across the Australian sheep flock.

Multiparatopic antibodies induce targeted downregulation of programmed death-ligand 1.

Programmed death-ligand 1 (PD-L1) drives inhibition of antigen-specific T cell responses through engagement of its receptor programmed death-1 (PD-1) on activated T cells. Overexpression of these immune checkpoint proteins in the tumor microenvironment has motivated the design of targeted antibodies that disrupt this interaction. Despite clinical success of these antibodies, response rates remain low, necessitating novel approaches to enhance performance. Here, we report the development of antibody fusion proteins that block immune checkpoint pathways through a distinct mechanism targeting molecular trafficking. By engaging multiple receptor epitopes on PD-L1, our engineered multiparatopic antibodies induce rapid clustering, internalization, and degradation in an epitope- and topology-dependent manner. The complementary mechanisms of ligand blockade and receptor downregulation led to more durable immune cell activation and dramatically reduced PD-L1 availability in mouse tumors. Collectively, these multiparatopic antibodies offer mechanistic insight into immune checkpoint protein trafficking and how it may be manipulated to reprogram immune outcomes.

Tracking Cancer: Exploring Heart Rate Variability Patterns by Cancer Location and Progression.

Reduced heart rate variability (HRV) is an autonomic nervous system (ANS) response that may indicate dysfunction in the human body. Consistent evidence shows cancer patients elicit lower HRV; however, only select cancer locations were previously evaluated. Thus, the aim of the current study was to explore HRV patterns in patients diagnosed with and in varying stages of the most prevalent cancers. At a single tertiary academic medical center, 798 patients were recruited. HRV was measured via an armband monitor (Warfighter MonitorTM, Tiger Tech Solutions, Inc., Miami, FL, USA) equipped with electrocardiographic capabilities and was recorded for 5 to 7 min with patients seated in an upright position. Three time-domain metrics were calculated: SDNN (standard deviation of the NN interval), rMSSD (the root mean square of successive differences of NN intervals), and the percentage of time in which the change in successive NN intervals exceeds 50ms within a measurement (pNN50). Of the 798 patients, 399 were diagnosed with cancer. Cancer diagnoses were obtained via medical records one week following the measurement. Analysis of variance models were performed comparing the HRV patterns between different cancers, cancer stages (I-IV), and demographic strata. A total of 85% of the cancer patients had breast, gastrointestinal, genitourinary, or respiratory cancer. The cancer patients were compared to a control non-cancer patient population with similar patient size and distributions for sex, age, body mass index, and co-morbidities. For all HRV metrics, non-cancer patients exhibited significantly higher rMSSDs (11.1 to 13.9 ms, p < 0.0001), SDNNs (22.8 to 27.7 ms, p < 0.0001), and pNN50s (6.2 to 8.1%, p < 0.0001) compared to stage I or II cancer patients. This significant trend was consistently observed across each cancer location. Similarly, compared to patients with stage III or IV cancer, non-cancer patients possessed lower HRs (-11.8 to -14.0 bpm, p < 0.0001) and higher rMSSDs (+31.7 to +32.8 ms, p < 0.0001), SDNNs (+45.2 to +45.8 ms), p < 0.0001, and pNN50s (19.2 to 21.6%, p < 0.0001). The HR and HRV patterns observed did not significantly differ between cancer locations (p = 0.96 to 1.00). The depressed HRVs observed uniformly across the most prevalent cancer locations and stages appeared to occur independent of patients' co-morbidities. This finding highlights the potentially effective use of HRV as a non-invasive tool for determining common cancer locations and their respective stages. More studies are needed to delineate the HRV patterns across different ages, between sexes and race/ethnic groups.

Automatic Mechanical Ventilation vs Manual Bag Ventilation During CPR: A Pilot Randomized Controlled Trial.

BACKGROUND: There is insufficient evidence supporting the theory that mechanical ventilation can replace the manual ventilation method during CPR. RESEARCH QUESTION: Is using automatic mechanical ventilation feasible and comparable to the manual ventilation method during CPR? STUDY DESIGN AND METHODS: This pilot randomized controlled trial compared automatic mechanical ventilation (MV) and manual bag ventilation (BV) during CPR of out-of-hospital cardiac arrest (OHCA). Patients with medical OHCA arriving at the ED were randomly assigned to two groups: an MV group using a mechanical ventilator and a BV group using Ambu-bag. Primary outcome was any return-of-spontaneous circulation (ROSC). Secondary outcomes were changes of arterial blood gas analysis results during CPR. Tidal volume, minute volume, and peak airway pressure were also analyzed. RESULTS: A total of 60 patients were enrolled, and 30 patients were randomly assigned to each group. There were no statistically significant differences in basic characteristics of OHCA patients between the two groups. The rate of any ROSC was 56.7% in the MV group and 43.3% in the BV group, indicating no significant (P = .439) difference between the two groups. There were also no statistically significant differences in changes of PH, Pco2, Po2, HCO3, or lactate levels during CPR between the two groups (P values = .798, 0.249, .515, .876, and .878, respectively). Significantly lower VT (P < .001) and minute volume (P = .009) were observed in the MV group. INTERPRETATION: In this pilot trial, the use of MV instead of BV during CPR was feasible and could serve as a viable alternative. A multicenter randomized controlled trial is needed to create sufficient evidence for ventilation guideline during CPR. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT05550454; URL: www. CLINICALTRIALS: gov.

Ruminant metabolism of zygacine, the major toxic alkaloid in foothill death camas (Zigadenuspaniculatus).

Death Camas (Zigadenus spp.) are common poisonous plants distributed throughout North America. The toxic alkaloids in foothill death camas are zygadenine and a series of zygadenine esters, with zygacine, the 3-acetyl ester of zygadenine, being the most abundant. Both cattle and sheep can be poisoned by grazing death camas, however, sheep consume death camas more readily and are most often poisoned. We hypothesized that the presence of enzymes, including esterases present in the rumen, liver, and blood of livestock would metabolize zygacine. The objective of this study was to investigate the metabolism of zygacine in sheep and cattle using in-vitro and in-vivo systems. Results from experiments where zygacine was incubated in rumen culture, plasma, liver S9 fractions, and liver microsomes and from the analysis of rumen and sera from sheep and cattle dosed death camas plant material demonstrated that zygacine is metabolized to zygadenine in the rumen, liver and blood of sheep and cattle. The results from this study indicate that diagnosticians should analyze for zygadenine, and not zygacine, in the rumen and sera for the diagnosis of livestock suspected to have been poisoned by foothill death camas.

A Novel Polymer-Encapsulated Multi-Imaging Modality Fiducial Marker with Positive Signal Contrast for Image-Guided Radiation Therapy.

BACKGROUND: Current fiducial markers (FMs) in external-beam radiotherapy (EBRT) for prostate cancer (PCa) cannot be positively visualized on magnetic resonance imaging (MRI) and create dose perturbation and significant imaging artifacts on computed tomography (CT) and MRI. We report our initial experience with clinical imaging of a novel multimodality FM, NOVA. METHODS: We tested Gold Anchor [G-FM], BiomarC [carbon, C-FM], and NOVA FMs in phantoms imaged with kilovoltage (kV) X-rays, transrectal ultrasound (TRUS), CT, and MRI. Artifacts of the FMs on CT were quantified by the relative streak artifacts level (rSAL) metric. Proton dose perturbations (PDPs) were measured with Gafchromic EBT3 film, with FMs oriented either perpendicular to or parallel with the beam axis. We also tested the performance of NOVA-FMs in a patient. RESULTS: NOVA-FMs were positively visualized on all 4 imaging modalities tested. The rSAL on CT was 0.750 ± 0.335 for 2-mm reconstructed slices. In F-tests, PDP was associated with marker type and depth of measurement (p < 10-6); at 5-mm depth, PDP was significantly greater for the G-FM (12.9%, p = 10-6) and C-FM (6.0%, p = 0.011) than NOVA (4.5%). EBRT planning with MRI/CT image co-registration and daily alignments using NOVA-FMs in a patient was feasible and reproducible. CONCLUSIONS: NOVA-FMs were positively visible and produced less PDP than G-FMs or C-FMs. NOVA-FMs facilitated MRI/CT fusion and identification of regions of interest.

Effects of Transport to Trauma Centers on Survival Outcomes Among Severe Trauma Patients in Korea: Nationwide Age-Stratified Analysis.

BACKGROUND: Previous studies showed that the prognosis for severe trauma patients is better after transport to trauma centers compared to non-trauma centers. However, the benefit from transport to trauma centers may differ according to age group. The aim of this study was to compare the effects of transport to trauma centers on survival outcomes in different age groups among severe trauma patients in Korea. METHODS: Cross-sectional study using Korean national emergency medical service (EMS) based severe trauma registry in 2018-2019 was conducted. EMS-treated trauma patients whose injury severity score was above or equal to 16, and who were not out-of-hospital cardiac arrest or death on arrival were included. Patients were classified into 3 groups: pediatrics (age < 19), working age (age 19-65), and elderly (age > 65). The primary outcome was in-hospital mortality. Multivariable logistic regression analysis was conducted to evaluate the effect of trauma center transport on outcome after adjusting of age, sex, comorbidity, mechanism of injury, Revised Trauma Score, and Injury Severity Score. All analysis was stratified according to the age group, and subgroup analysis for traumatic brain injury was also conducted. RESULTS: Overall, total of 10,511 patients were included in the study, and the number of patients in each age group were 488 in pediatrics, 6,812 in working age, and 3,211 in elderly, respectively. The adjusted odds ratio (95% confidence interval [CI]) of trauma center transport on in-hospital mortality from were 0.76 (95% CI, 0.43-1.32) in pediatrics, 0.78 (95% CI, 0.68-0.90) in working age, 0.71(95% CI, 0.60-0.85) in elderly, respectively. In subgroup analysis of traumatic brain injury, the benefit from trauma center transport was observed only in elderly group. CONCLUSION: We found out trauma centers showed better clinical outcomes for adult and elderly groups, excluding the pediatric group than non-trauma centers. Further research is warranted to evaluate and develop the response system for pediatric severe trauma patients in Korea.

A phase I study of Mirvetuximab Soravtansine and gemcitabine in patients with FRα-positive recurrent ovarian, primary peritoneal, fallopian tube, or endometrial cancer, or triple negative breast cancer.

OBJECTIVE: Platinum-resistant epithelial ovarian cancer (EOC), recurrent endometrial cancer (EC), and triple negative breast cancer (TNBC) are difficult to treat after failing standard therapies. This phase I study evaluated mirvetuximab soravtansine (MIRV) and gemcitabine in patients with recurrent FRα-positive EOC, EC, or TNBC to determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) (primary endpoint). METHODS: FRα-positive patients with platinum-resistant EOC, EC, or TNBC with ≤4 prior chemotherapy regimens (2 for EC) were enrolled. FRα expression requirement varied among eligible tumors and changed during the study. RESULTS: Twenty patients were enrolled; 17 were evaluable for DLT. Half the patients received ≥3 prior chemotherapy lines. Most EOC and EC patients (78%) were medium (50-74%) or high(75-100%) FRα expressors. TNBC patients were low (25-49%) FRα expressors. The MTD/RP2D was MIRV 6 mg/kg AIBW D1 and gemcitabine 800 mg/m2 IV, D1 and D8, every 21 days (Dose Level [DL] 3), where 5/7 patients demonstrated a partial response (PR) as their best response, including 2 confirmed ovarian responses whose time-to-progression and duration of response were 7.9/5.4 and 8.0/5.7 months respectively. Most common treatment-related adverse events at MTD were anemia and neutropenia (3/7 each, 43%), diarrhea, hypophosphatemia, thrombocytopenia, and leukopenia (2/7 each, 29%). DLTs were thrombocytopenia (DL1), oral mucositis (DL4) and diarrhea (DL4). Nine of 20 patients (45%; 95% CI: 21.1-68.9%) achieved PR as their best response, with 3/20 patients or 15% (95%CI, 0-32.1%) confirmed PR. CONCLUSION: MIRV and gemcitabine demonstrate promising activity in platinum resistant EOC at RP2D, but frequent hematologic toxicities.

Functional Cerebral Neurovascular Mapping During Focused Ultrasound Peripheral Neuromodulation of Neuropathic Pain.

BACKGROUND: Nociceptive pain is required for healthy function, yet, neuropathic pain (disease or injury) can be severely debilitating. Though a wide-array of treatment options are available, they are often systemic and/or invasive. As a promising neuromodulation treatment, Focused ultrasound (FUS) is a noninvasive and highly spatially-targeted technique shown to stimulate neural activity, yet, effects on pain signaling are currently unknown. OBJECTIVE: Develop and validate a method for studying FUS nerve stimulation modulation of pain-evoked neural responses in vivo. METHODS: We developed a high-resolution functional ultrasound (fUS) method capable of mapping cortical responses in healthy and neuropathic pain mice in response to FUS neuromodulation treatment. RESULTS: FUS-evoked hemodynamic responses are correlated with the intensity of peripheral neuromodulation. We confirm functional connectivity is altered in neuropathic mice and demonstrate that FUS can modulate neuropathic pain-evoked hemodynamics. CONCLUSIONS: The findings presented herein provides evidence for an FUS-based nerve pain method and validates the fUS technique developed for monitoring pain-evoked hemodynamics. SIGNIFICANCE: We anticipate that the findings presented herein describe a noninvasive and flexible nerve modulation technique for pain mitigation, furthering evidence for clinical translation.

Association between Case Volumes of Extracorporeal Life Support and Clinical Outcome in Out-of-Hospital Cardiac Arrest.

AIM: Extracorporeal life support (ECLS) for out-of-hospital cardiac arrest (OHCA) is increasing. There is little evidence identifying the association between hospital ECLS case volumes and outcomes in different populations receiving ECLS or conventional cardiopulmonary resuscitation (CPR). The goal of this investigation was to identify the association between ECLS case volumes and clinical outcomes of OHCA patients. METHODS: This cross-sectional observational study used the National OHCA Registry for adult OHCA cases in Seoul, Korea between January 2015 and December 2019. If the ECLS volume during the study period was >20, the institution was defined as a high-volume ECLS center. Others were defined as low-volume ECLS centers. Outcomes were good neurologic recovery (cerebral performance category 1 or 2) and survival to discharge. We performed multivariate logistic regression and interaction analyses to assess the association between case volume and clinical outcome. RESULTS: Of the 17,248 OHCA cases, 3,731 were transported to high-volume centers. Among the patients who underwent ECLS, those at high-volume centers had a higher neurologic recovery rate than those at low-volume centers (17.0% vs. 12.0%), and the adjusted OR for good neurologic recovery was 2.22 (95% confidence interval (CI): 1.15-4.28) in high-volume centers compared to low-volume centers. For patients who received conventional CPR, high-volume centers also showed higher survival-to-discharge rates (adjusted OR of 1.16, 95%CI: 1.01-1.34). CONCLUSIONS: High-volume ECLS centers showed better neurological recovery in patients who underwent ECLS. High-volume centers also had better survival-to-discharge rates than low-volume centers for patients not receiving ECLS.

Secondary Prevention Therapies in Real-World Patients with Myocardial Infarction: Eligibility Based on Randomized Trials Supporting European and American Guidelines.

OBJECTIVE: We aimed to evaluate the applicability of the eligibility criteria of randomized controlled trials (RCTs) cited in guideline recommendations in a real-world cohort of patients receiving secondary prevention after acute myocardial infarction from the EPICOR registries. METHODS: Recommendations provided by American and European guidelines for acute myocardial infarction were classified into general (applying to all patients) and specific (applying to patients with left ventricular dysfunction or heart failure). Randomized controlled trials cited in these recommendations were selected, and their entry criteria were applied to our international cohort of 18,117 patients. RESULTS: There were 91.5% patients eligible for beta blockers (84.6% for general, and 5.9% for specific recommendations), 97.7% eligible for renin-angiotensin system inhibitor (angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers [ACEI/ARB]) recommendations (69.9% for general, 27.9% for specific) and 4.1% eligible for mineralocorticoid receptor antagonists (only specific recommendations). The percentages of patients with eligibility criteria who were discharged with a prescription of the recommended therapies were 80%-85% for beta blockers, 70%-75% for ACEI/ARB, and 29% for mineralocorticoid receptor antagonists. There were large regional variations in the percentage of eligible patients and in those receiving the medications (eg, 95% in Northern Europe and 57% in Southeast Asia for beta blockers). CONCLUSION: Most real-world acute myocardial infarction patients are eligible for secondary prevention therapy in both general and specific guideline recommendations, and the percentage of those on beta blockers and ACEI/ARB at hospital discharge is high. There are large regional variations in the proportion of patients receiving recommended therapies. Local targeted interventions are needed for quality improvement.

Equivalent-time-active-cavitation-imaging enables vascular-resolution blood-brain-barrier-opening-therapy planning.

Objective. Linking cavitation and anatomy was found to be important for predictable outcomes in focused-ultrasound blood-brain-barrier-opening and requires high resolution cavitation mapping. However, cavitation mapping techniques for planning and monitoring of therapeutic procedures either (1) do not leverage the full resolution capabilities of ultrasound imaging or (2) place constraints on the length of the therapeutic pulse. This study aimed to develop a high-resolution technique that could resolve vascular anatomy in the cavitation map.Approach. Herein, we develop BandPass-sampled-equivalent-time-active-cavitation-imaging (BP-ETACI), derived from bandpass sampling and dual-frequency contrast imaging at 12.5 MHz to produce cavitation maps prior and during blood-brain barrier opening with long therapeutic bursts using a 1.5 MHz focused transducer in the brain of C57BL/6 mice.Main results. The BP-ETACI cavitation maps were found to correlate with the vascular anatomy in ultrasound localization microscopy vascular maps and in histological sections. Cavitation maps produced from non-blood-brain-barrier disrupting doses showed the same cavitation-bearing vasculature as maps produced over entire blood-brain-barrier opening procedures, allowing use for (1) monitoring focused-ultrasound blood-brain-barrier-opening (FUS-BBBO), but also for (2) therapy planning and target verification.Significance. BP-ETACI is versatile, created high resolution cavitation maps in the mouse brain and is easily translatable to existing FUS-BBBO experiments. As such, it provides a means to further study cavitation phenomena in FUS-BBBO.