Cingulate cortex facilitates auditory perception under challenging listening conditions.

We often exert greater cognitive resources (i.e., listening effort) to understand speech under challenging acoustic conditions. This mechanism can be overwhelmed in those with hearing loss, resulting in cognitive fatigue in adults, and potentially impeding language acquisition in children. However, the neural mechanisms that support listening effort are uncertain. Evidence from human studies suggest that the cingulate cortex is engaged under difficult listening conditions, and may exert top-down modulation of the auditory cortex (AC). Here, we asked whether the gerbil cingulate cortex (Cg) sends anatomical projections to the AC that facilitate perceptual performance. To model challenging listening conditions, we used a sound discrimination task in which stimulus parameters were presented in either 'Easy' or 'Hard' blocks (i.e., long or short stimulus duration, respectively). Gerbils achieved statistically identical psychometric performance in Easy and Hard blocks. Anatomical tracing experiments revealed a strong, descending projection from layer 2/3 of the Cg1 subregion of the cingulate cortex to superficial and deep layers of primary and dorsal AC. To determine whether Cg improves task performance under challenging conditions, we bilaterally infused muscimol to inactivate Cg1, and found that psychometric thresholds were degraded for only Hard blocks. To test whether the Cg-to-AC projection facilitates task performance, we chemogenetically inactivated these inputs and found that performance was only degraded during Hard blocks. Taken together, the results reveal a descending cortical pathway that facilitates perceptual performance during challenging listening conditions. Significance Statement: Sensory perception often occurs under challenging conditions, such a noisy background or dim environment, yet stimulus sensitivity can remain unaffected. One hypothesis is that cognitive resources are recruited to the task, thereby facilitating perceptual performance. Here, we identify a top-down cortical circuit, from cingulate to auditory cortex in the gerbils, that supports auditory perceptual performance under challenging listening conditions. This pathway is a plausible circuit that supports effortful listening, and may be degraded by hearing loss.

Fitting and validation of an agent-based model for COVID-19 case forecasting in workplaces and universities.

COVID-19 forecasting models have been critical in guiding decision-making on surveillance testing, social distancing, and vaccination requirements. Beyond influencing public health policies, an accurate COVID-19 forecasting model can impact community spread by enabling employers and university leaders to adapt worksite policies and practices to contain or mitigate outbreaks. While many such models have been developed for COVID-19 forecasting at the national, state, county, or city level, only a few models have been developed for workplaces and universities. Furthermore, COVID-19 forecasting models have rarely been validated against real COVID-19 case data. Here we present the systematic parameter fitting and validation of an agent-based compartment model for the forecasting of daily COVID-19 cases in single-site workplaces and universities with real-world data. Our approaches include manual fitting, where initial model parameters are chosen based on historical data, and automated fitting, where parameters are chosen based on candidate case trajectory simulations that result in best fit to prevalence estimation data. We use a 14-day fitting window and validate our approaches on 7- and 14-day testing windows with real COVID-19 case data from one employer. Our manual and automated fitting approaches accurately predicted COVID-19 case trends and outperformed the baseline model (no parameter fitting) across multiple scenarios, including a rising case trajectory (RMSLE values: 2.627 for baseline, 0.562 for manual fitting, 0.399 for automated fitting) and a decreasing case trajectory (RMSLE values: 1.155 for baseline, 0.537 for manual fitting, 0.778 for automated fitting). Our COVID-19 case forecasting model allows decision-makers at workplaces and universities to proactively respond to case trend forecasts, mitigate outbreaks, and promote safety.

Increases in hydraulic conductance and solute permeability in a mouse model of ascending thoracic aortic aneurysm.

Large elastic arteries, such as the aorta, contain concentric layers of elastic laminae composed mainly of the extracellular matrix protein elastin. The structure of the elastic laminae could affect transmural mass transport and contribute to aortic disease progression. We studied the effects of a genetic mutation (LoxM292R/+, referred to as MU) in mice associated with ascending thoracic aortic aneurysm (TAA) on the mass transport and elastic laminae structure. Solute absent fluid flux and hydraulic conductance through the ascending aortic wall were not significantly different between groups, however solute present fluid flux, hydraulic conductance, solute flux, and solute permeability of 4 kDa FITC-dextran were significantly increased in the MU group, indicating that movement of small molecules into the aortic wall is facilitated in MU mice. Quantification from light microscopy images of the ascending aorta showed no significant differences in wall thickness, or inner elastic lamina fenestration size and density, but an increase in the number of elastic laminae breaks in the MU group. Ultrastructural comparisons from transmission electron micrographs suggest less dense and disorganized elastic laminae in MU aorta that may also contribute to the transport differences. Our results provide an initial investigation into the connections between mass transport and elastic laminae structure, specifically in a genetic mouse aneurysm model, which can be further used to understand TAA pathology and develop treatment strategies.

A Career Life-Cycle Perspective on Women's Health and Safety: Insights From the Defense Health Board Report on Military Women's Health.

OBJECTIVE: Women's health has demanded more attention from employers as women integrated into the workforce. Traditionally male-dominant fields and occupations require special attention to workplace design, physical standards for entry, employment practices, equipment, and health monitoring. This editorial summarizes the Defense Health Board's (DHB) review of Active Duty Women's Health and its recommendations grounded in a woman's career life-cycle. METHODS: The DHB reviewed the Department of Defense and foreign militaries' current women's health services, relevant policies and practices, peer-reviewed scientific literature, and subject matter expert interviews. RESULTS: The DHB's recommendations centered on a comprehensive approach to education, health care access and treatment, professional workforce development, workplace standards and equipment, and accountable outcomes metrics to guide improvement. CONCLUSIONS: Employers can learn how to reduce morbidity, leading to a healthier and more productive female workforce.

Mobilizing the U.S. Military's TRICARE Program for Value-Based Care: A Report From the Defense Health Board.

The U.S. Military Health System spends about $50 billion annually to provide care to 9.6 million active duty service members, retirees, and their families through its TRICARE health plans. TRICARE follows the predominant payment model in the USA-fee-for-service-although the Department of Defense (DoD) and Congress encourage and mandate a move toward alternative payment models-mainly, fee-for-value. For the next TRICARE contracts which will begin in 2023, the DoD asked its health-focused federal advisory committee, the Defense Health Board (DHB), to recommend how best to assess and prioritize leading value-based healthcare initiatives identified from private, public, and employer-based health plans. The November 2020 report, 'Modernization of the TRICARE Benefit', specifies a rubric to evaluate these value-based care initiatives not only in traditional measures of effectiveness but also in terms of the Defense Health Agency's Quadruple Aim with its focus on readiness. The goal of TRICARE's move toward value-based care is to leverage its size and focus on prevention of disease and injury to maintain the readiness of the U.S. Armed Forces in addition to delivering great outcomes and value to the DoD's nearly 10 million beneficiaries. The DHB emphasizes that TRICARE's size and focus on providing quality care at lower cost will incentivize providers to participate in the shift toward value-based care despite the potential challenges in transitioning to this system. This shift also aims to motivate other large government and private payors to accelerate the adoption of value-based care through TRICARE's example.

A holistic approach for suppression of COVID-19 spread in workplaces and universities.

As society has moved past the initial phase of the COVID-19 crisis that relied on broad-spectrum shutdowns as a stopgap method, industries and institutions have faced the daunting question of how to return to a stabilized state of activities and more fully reopen the economy. A core problem is how to return people to their workplaces and educational institutions in a manner that is safe, ethical, grounded in science, and takes into account the unique factors and needs of each organization and community. In this paper, we introduce an epidemiological model (the "Community-Workplace" model) that accounts for SARS-CoV-2 transmission within the workplace, within the surrounding community, and between them. We use this multi-group deterministic compartmental model to consider various testing strategies that, together with symptom screening, exposure tracking, and nonpharmaceutical interventions (NPI) such as mask wearing and physical distancing, aim to reduce disease spread in the workplace. Our framework is designed to be adaptable to a variety of specific workplace environments to support planning efforts as reopenings continue. Using this model, we consider a number of case studies, including an office workplace, a factory floor, and a university campus. Analysis of these cases illustrates that continuous testing can help a workplace avoid an outbreak by reducing undetected infectiousness even in high-contact environments. We find that a university setting, where individuals spend more time on campus and have a higher contact load, requires more testing to remain safe, compared to a factory or office setting. Under the modeling assumptions, we find that maintaining a prevalence below 3% can be achieved in an office setting by testing its workforce every two weeks, whereas achieving this same goal for a university could require as much as fourfold more testing (i.e., testing the entire campus population twice a week). Our model also simulates the dynamics of reduced spread that result from the introduction of mitigation measures when test results reveal the early stages of a workplace outbreak. We use this to show that a vigilant university that has the ability to quickly react to outbreaks can be justified in implementing testing at the same rate as a lower-risk office workplace. Finally, we quantify the devastating impact that an outbreak in a small-town college could have on the surrounding community, which supports the notion that communities can be better protected by supporting their local places of business in preventing onsite spread of disease.

Patterns of use and perceived value of social media for population health among population health stakeholders: a cross-sectional web-based survey.

BACKGROUND: Although existing studies have described patterns of social media use in healthcare, most are focused on health professionals in one discipline. Population health requires a multi-disciplinary approach to ensure diversity and to include diverse stakeholders. To date, what is known about using social media in population health is focused on its potential as a communication tool. This study aims to investigate patterns of use and perceived value of social media usage among stakeholders in population health practice, policy, or research. METHODS: We conducted a web-based survey of delegates attending the Singapore Population Health Conversations and Workshop. We designed a 24-item questionnaire to assess 1) social media use in terms of type of platform and frequency of use; 2) perceptions of social media relevance and impact on population health; and 3) top three areas in population health that would benefit from social media. We used descriptive and logistic regression analyses to assess the relationships between variables. RESULTS: Of the 308 survey respondents, 97.7% reported that they use social media in some form. Messaging (96.8%) was the most dominant activity when using social media. Challenges in implementing social media for population health were time investment by health care professionals (56.2%) and patient adoption (52.9%). The top three population health areas that would benefit most from using social media were the promotion of healthy behaviors (60.7%), community engagement (47.7%), and preventive care (40.6%). Older respondents (> = 40 years) were less likely to view social media as useful for the promotion of healthy behaviors (OR = 0.34; 95% CI: 0.19-0.60). Non-social/healthcare professionals were more likely to consider social media to be useful for community engagement (OR = 1.74; 95% CI: 1.10-2.76). For preventive care, older respondents (OR = 0.51; 95% CI: 0.32-0.82) and non-social/healthcare professionals were less likely to view social media as useful (OR = 0.61; 95% CI: 0.38-0.97). CONCLUSIONS: Our findings suggest that it may be important to select the specific care areas that would benefit most from using social media. The time investment needed by population health professionals should be fully addressed in planning to maximize the application and potential value of social media.

Exercise-induced calf muscle hyperemia: Rapid mapping of magnetic resonance imaging using deep learning approach.

Exercise-induced hyperemia in calf muscles was recently shown to be quantifiable with high-resolution magnetic resonance imaging (MRI). However, processing of the MRI data to obtain muscle-perfusion maps is time-consuming. This study proposes to substantially accelerate the mapping of muscle perfusion using a deep-learning method called artificial neural network (NN). Forty-eight MRI scans were acquired from 21 healthy subjects and patients with peripheral artery disease (PAD). For optimal training of NN, different training-data sets were compared, investigating the effect of data diversity and reference perfusion accuracy. Reference perfusion was estimated by tracer kinetic model fitting initialized with multiple values (multigrid model fitting). Result: The NN method was much faster than tracer kinetic model fitting. To generate a perfusion map of matrix 128 × 128 on a same computer, multigrid model fitting took about 80 min, single-grid or regular model fitting about 3 min, while the NN method took about 1 s. Compared to the reference values, NN trained with a diverse group gave estimates with mean absolute error (MAE) of 15.9 ml/min/100g and correlation coefficient (R) of 0.949, significantly more accurate than regular model fitting (MAE 22.3 ml/min/100g, R 0.889, p < .001). Conclusion: the NN method enables rapid perfusion mapping, and if properly trained, estimates perfusion with accuracy comparable to multigrid model fitting.

Renal perfusion imaging by MRI.

Renal perfusion can be quantitatively assessed by multiple magnetic resonance imaging (MRI) methods, including dynamic contrast enhanced (DCE), arterial spin labeling (ASL), and diffusion-weighted imaging with intravoxel incoherent motion (IVIM) analysis. In this review we summarize the advances in the field of renal-perfusion MRI over the past 5 years. The review starts with a brief introduction of relevant MRI methods, followed by a discussion of recent technical developments. In the main section of the review, we examine the clinical and preclinical applications for three disease populations: chronic kidney disease, renal transplant, and renal tumors. The DCE method has been routinely used for assessing renal tumors but not other renal diseases. As a noncontrast alternative, ASL was extensively explored in both preclinical and clinical applications and showed much promise. Protocol standardization for the methods is desperately needed, and then large-scale clinical trials for the methods can be initiated prior to their broad clinical use. Level of Evidence: 5 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019. J. Magn. Reson. Imaging 2020;52:369-379.

Intracellular retention of mutant lysyl oxidase leads to aortic dilation in response to increased hemodynamic stress.

Heterozygous missense mutations in lysyl oxidase (LOX) are associated with thoracic aortic aneurysms and dissections. To assess how LOX mutations modify protein function and lead to aortic disease, we studied the factors that influence the onset and progression of vascular aneurysms in mice bearing a Lox mutation (p.M292R) linked to aortic dilation in humans. We show that mice heterozygous for the M292R mutation did not develop aneurysmal disease unless challenged with increased hemodynamic stress. Vessel dilation was confined to the ascending aorta although both the ascending and descending aortae showed changes in vessel wall structure, smooth muscle cell number and inflammatory cell recruitment that differed between wild-type and mutant animals. Studies with isolated cells found that M292R-mutant Lox is retained in the endoplasmic reticulum and ultimately cleared through an autophagy/proteasome pathway. Because the mutant protein does not transit to the Golgi where copper incorporation occurs, the protein is never catalytically active. These studies show that the M292R mutation results in LOX loss-of-function due to a secretion defect that predisposes the ascending aorta in mice (and by extension humans with similar mutations) to arterial dilation when exposed to risk factors that impart stress to the arterial wall.

Exercise-stimulated arterial transit time in calf muscles measured by dynamic contrast-enhanced magnetic resonance imaging.

The primary goal of this study was to evaluate arterial transit time (ATT) in exercise-stimulated calf muscles as a promising indicator of muscle function. Following plantar flexion, ATT was measured by dynamic contrast-enhanced (DCE) MRI in young and elderly healthy subjects and patients with peripheral artery disease (PAD). In the young healthy subjects, gastrocnemius ATT decreased significantly (P < 0.01) from 4.3 ± 1.5 to 2.4 ± 0.4 sec when exercise load increased from 4 lbs to 16 lbs. For the same load of 4 lbs, gastrocnemius ATT was lower in the elderly healthy subjects (3.2 ± 1.1 sec; P = 0.08) and in the PAD patients (2.4 ± 1.2 sec; P = 0.02) than in the young healthy subjects. While the sensitivity of the exercise-stimulated ATT is diagnostically useful, it poses a challenge for arterial spin labeling (ASL), a noncontrast MRI method for measuring muscle perfusion. As a secondary goal of this study, we assessed the impact of ATT on ASL-measured perfusion with ASL data of multiple post labeling delays (PLDs) acquired from a healthy subject. Perfusion varied substantially with PLD in the activated gastrocnemius, which can be attributed to the ATT variability as verified by a simulation. In conclusion, muscle ATT is sensitive to exercise intensity, and it potentially reflects the functional impact of aging and PAD on calf muscles. For precise measurement of exercise-stimulated muscle perfusion, it is recommended that ATT be considered when quantifying muscle ASL data.

Exercise-induced calf muscle hyperemia: quantitative mapping with low-dose dynamic contrast enhanced magnetic resonance imaging.

Peripheral artery disease (PAD) in the lower extremities often leads to intermittent claudication. In the present study, we proposed a low-dose DCE MRI protocol for quantifying calf muscle perfusion stimulated with plantar flexion and multiple new metrics for interpreting perfusion maps, including the ratio of gastrocnemius over soleus perfusion (G/S; for assessing the vascular redistribution between the two muscles) and muscle perfusion normalized by whole body perfusion (for quantifying the muscle's active hyperemia). Twenty-eight human subjects participated in this Institutional Review Board-approved study, with 10 healthy subjects ( group A) for assessing interday reproducibility and 8 healthy subjects ( group B) for exploring the relationship between plantar-flexion load and induced muscle perfusion. In a pilot group of five elderly healthy subjects and five patients with PAD ( group C), we proposed a protocol that measured perfusion for a low-intensity exercise and for an exhaustion exercise in a single MRI session. In group A, perfusion estimates for calf muscles were highly reproducible, with correlation coefficients of 0.90-0.93. In group B, gastrocnemius perfusion increased linearly with the exercise workload ( P < 0.05). With the low-intensity exercise, patients with PAD in group C showed substantially lower gastrocnemius perfusion compared with elderly healthy subjects [43.4 (SD 23.5) vs. 106.7 (SD 73.2) ml·min-1·100 g-1]. With exhaustion exercise, G/S [1.0 (SD 0.4)] for patients with PAD was lower than both its low-intensity level [1.9 (SD 1.3)] and the level in elderly healthy subjects [2.7 (SD 2.1)]. In conclusion, the proposed MRI protocol and the new metrics are feasible for quantifying exercise-induced muscle hyperemia, a promising functional test of PAD. NEW & NOTEWORTHY To quantitatively map exercise-induced hyperemia in calf muscles, we proposed a high-resolution MRI method shown to be highly reproducible and sensitive to exercise load. With the use of low contrast, it is feasible to measure calf muscle hyperemia for both low-intensity and exhaustion exercises in a single MRI session. The newly proposed metrics for interpreting perfusion maps are promising for quantifying intermuscle vascular redistribution or a muscle's active hyperemia.

Sampling arterial input function (AIF) from peripheral arteries: Comparison of a temporospatial-feature based method against conventional manual method.

It is often difficult to accurately localize small arteries in images of peripheral organs, and even more so with vascular abnormality vasculatures, including collateral arteries, in peripheral artery disease (PAD). This poses a challenge for manually sampling arterial input function (AIF) in quantifying dynamic contrast-enhanced (DCE) MRI data of peripheral organs. In this study, we designed a multi-step screening approach that utilizes both the temporal and spatial information of the dynamic images, and is presumably suitable for localizing small and unpredictable peripheral arteries. In 41 DCE MRI datasets acquired from human calf muscles, the proposed method took <5 s on average for sampling AIF for each case, much more efficient than the manual sampling method; AIFs by the two methods were comparable, with Pearson's correlation coefficient of 0.983 ±â€¯0.004 (p-value < 0.01) and relative difference of 2.4% ±â€¯2.6%. In conclusion, the proposed temporospatial-feature based method enables efficient and accurate sampling of AIF from peripheral arteries, and would improve measurement precision and inter-observer consistency for quantitative DCE MRI of peripheral tissues.

Enhancing Value of MRI: A Call for Action.

As national healthcare spending has spiraled out of control, payment reform that moves from volume to value-based payment has been introduced as a practical solution. Under alternative value-based payment models, physicians and clinical teams must deliver the best care possible at a lower cost. Medical imaging has changed the way we diagnose disease, evaluate severity, assess treatment effects, and provide biological insights for the pathophysiology of many diseases. Over the past 50 years, imaging techniques have become increasingly advanced-from X-ray to computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and multi-modal imaging. Advanced imaging such as MRI has given clinicians remarkable insights into medical conditions and saved innumerable lives. Under the value proposition, however, we must ask if each imaging study changes treatment decisions, improves patient outcomes, and is cost-effective. Imaging research has been focused on developing new technologies and clinical applications to assess diagnostic accuracy. What is needed is the higher-level technology assessment. In this article we review why we need to demonstrate the value of MRI, how we define value, what strategies can enhance MR value through partnership with various stakeholders, and how imaging scientists can contribute to healthcare delivery in the future. Level of Evidence: 5 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;49:e40-e48.

Diagnostic Accuracy of Noncontrast MR Angiography Protocols at 3T for the Detection and Characterization of Lower Extremity Peripheral Arterial Disease.

PURPOSE: To compare the diagnostic accuracy of established non-gadolinium (Gd)-enhanced magnetic resonance (MR) angiography protocols with Gd-enhanced MR angiography at 3T for evaluating lower extremity peripheral arterial disease (PAD). MATERIALS AND METHODS: From February 2014 to 2015, 20 patients with PAD and intermittent claudication (16 men; age range, 51-76 y; Fontaine stage II) underwent 3-station (abdominopelvic, thigh, and calf) non-Gd MR angiography and bolus-chase Gd MR angiography protocols performed at 3T (Siemens Tim Trio), including quiescent-interval single-shot (QISS) MR angiography for all 3 stations and a combination of quadruple inversion recovery (QIR) MR angiography for the abdominopelvic station and electrocardiogram-gated fast spin echo (ECG-FSE) MR angiography for the extremities. Two radiologists independently evaluated vessel segments for vascular stenosis, diagnosis confidence, graft presence, and Trans-Atlantic Inter-Society Consensus (TASC) II classification for each station. Diagnostic accuracies and κ agreement were assessed. RESULTS: Of 573 vascular segments imaged, 16.9% (97/573, 19/20 patients) demonstrated hemodynamically significant abnormalities. Reader confidence was sufficient for diagnosis in 98% of segments with Gd MR angiography, 93% with QIR/ECG-FSE, and 95% with QISS. Overall reader confidence was higher with QISS than QIR/ECG-FSE within all 3 stations combined (P < .05). With low-confidence segments treated as misdiagnosis, sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and κ agreement for all 3 stations combined were 81.4/87.2/57.0/95.8/86.2%/0.578 for QIR/ECG-FSE and 75.0/90.6/61.6/94.7/88.0%/0.597 for QISS. Using TASC II criteria to assess severity, QISS and QIR/ECG-FSE had no statistical difference in agreement with Gd MR angiography. CONCLUSIONS: QISS and QIR/ECG-FSE MR angiography protocols demonstrate comparable diagnostic accuracies with high specificity. Either protocol provides an alternative to Gd MR angiography at 3T for patients with PAD.

Financial Analysis of Pediatric Resident Physician Primary Care Longitudinal Outpatient Experience.

OBJECTIVE: To determine whether residency training represents a net positive or negative cost to academic medical centers, we analyzed the cost of a residency program and clinical productivity of residents and faculty in an outpatient primary care practice with or without residents. METHODS: Patient volume and revenue data (Current Procedural Terminology codes) from an academic primary care general pediatric clinic were evaluated for faculty clinics (faculty only) and resident teaching clinics (longitudinal outpatient experience [LOE]) with 1 to 4 residents per faculty. A detailed cost per resident was determined using a departmental financial model that included salary, benefits, faculty and administrative staff effort, nonpersonnel costs, and institutional graduate medical education support. RESULTS: The LOE clinics had a greater mean number of patient visits (11.6 vs 6.8) than faculty clinics per faculty member. In the LOE clinic, the number of patient visits per clinic was directly proportional to the number of residents per faculty. The cost for each resident was $250 per clinic ($112 per resident, $88 per medical assistant per resident, and $50 per room per resident). When factoring in clinic costs and faculty supervision time, the LOE clinics (average 3.5 residents with 1 supervising faculty) had greater average cost (+$687.00) and revenue (+$319.45) and lower operating margin (revenue minus cost, -$367.55) than the faculty clinics (1 faculty member). CONCLUSIONS: Pediatric resident LOE clinics had a greater average number of patient visits and revenue per faculty member but higher costs and lower operating margins than faculty clinics.

Magnetic Resonance Imaging of the Fibrotic Kidney.

Magnetic resonance imaging (MRI) has been used for many years for anatomic evaluation of the kidney. Recently developed methods attempt to go beyond anatomy to give information about the health and function of the kidneys. Several methods, including diffusion-weighted MRI, renal blood oxygen level-dependent MRI, renal MR elastography, and renal susceptibility imaging, show promise for providing unique insight into kidney function and severity of fibrosis. However, substantial limitations in accuracy and practicality limit the immediate clinical application of each method. Further development and improvement are necessary to achieve the ideal of a noninvasive image-based measure of renal fibrosis. Our brief review provides a short explanation of these emerging MRI methods and outlines the promising initial results obtained with each as well as current limitations and barriers to clinical implementation.