Ventromedial prefrontal cortex activation and neurofeedback modulation during episodic future thinking for individuals with suicidal thoughts and behaviors.

Individuals experiencing suicidal thoughts and behaviors (STBs) show less specificity and positivity during episodic future thinking (EFT). Here, we present findings from two studies aiming to (1) further our understanding of how STBs may relate to neural responsivity during EFT and (2) examine the feasibility of modulating EFT-related activation using real-time fMRI neurofeedback (rtfMRI-nf). Study 1 involved 30 individuals with major depressive disorder (MDD; half with STBs) who performed an EFT task during fMRI, for which they imagined personally-relevant future positive, negative, or neutral events. Positive EFT elicited greater ventromedial prefrontal cortex (vmPFC) activation compared to negative EFT. Importantly, the MDD + STB group exhibited reduced vmPFC activation across all EFT conditions compared to MDD-STB; although EFT fluency and subjective experience remained consistent across groups. Study 2 included rtfMRI-nf focused on vmPFC modulation during positive EFT for six participants with MDD + STBs. Results support the feasibility and acceptability of the rtfMRI-nf protocol and quantitative and qualitative observations are provided to help inform future, larger studies aiming to examine similar neurofeedback protocols. Results implicate vmPFC blunting as a promising treatment target for MDD + STBs and suggest rtfMRI-nf as one potential technique to explore for enhancing vmPFC engagement.

Preclinical validation of the advection diffusion flow estimation method using computational patient specific coronary tree phantoms.

Coronary computed tomography angiography (CCTA) does not allow the quantification of reduced blood flow due to coronary artery disease (CAD). In response, numerical methods based on the CCTA image have been developed to compute coronary blood flow and assess the impact of disease. However to compute blood flow in the coronary arteries, numerical methods require specification of boundary conditions that are difficult to estimate accurately in a patient-specific manner. We describe herein a new noninvasive flow estimation method, called Advection Diffusion Flow Estimation (ADFE), to compute coronary artery flow from CCTA to use as boundary conditions for numerical models of coronary blood flow. ADFE uses image contrast variation along the tree-like structure to estimate flow in each vessel. For validating this method we used patient specific software phantoms on which the transport of contrast was simulated. This controlled validation setting enables a direct comparison between estimated flow and actual flow and a detailed investigation of factors affecting accuracy. A total of 10 CCTA image data sets were processed to extract all necessary information for simulating contrast transport. A spectral element method solver was used for computing the ground truth simulations with high accuracy. On this data set, the ADFE method showed a high correlation coefficient of 0.998 between estimated flow and the ground truth flow together with an average relative error of only 1 % . Comparing the ADFE method with the best method currently available (TAFE) for image-based blood flow estimation, which showed a correlation coefficient of 0.752 and average error of 20 % , it can be concluded that the ADFE method has the potential to significantly improve the quantification of coronary artery blood flow derived from contrast gradients in CCTA images.

Levels of support for legislative bans to end physical punishment in schools and homes in a national sample.

OBJECTIVES: Physical punishment of children remains quite common and yet has only negative effects on children's health, making it an important public health problem. This study was designed to assess positive attitudes about and perceived normative support for the use of physical punishment with children, as well as attitudes regarding prohibition of physical punishment in homes and schools. STUDY DESIGN: This was a cross-sectional national survey of a diverse sample of US adults (N = 3049). METHODS: This survey, conducted in Fall 2020, assessed attitudes and perceived norms regarding physical punishment use using continuous measures as well as support and perceived support for policies prohibiting physical punishment in homes and schools in the United States. RESULTS: Respondents who had positive attitudes toward physical punishment (39%) and who perceived normative support for physical punishment (41%) were not in the majority. While 65% agreed that there should be a federal ban on physical punishment in public schools, only 18% perceived that most US adults would support such a ban. Persons who were older (aged ≥55 years), men, living in the southern United States, or who themselves were hit more frequently as children were significantly less likely than their counterparts to support a federal ban in schools. CONCLUSIONS: Based on a national sample, there is strong support for a federal ban on physical punishment in US schools; yet this normative belief is unrecognized. Social norms campaigns should capitalize on this pluralistic ignorance to increase mobilization toward policy reform and reduction of harm to children through bans of physical punishment in public schools.

The association of coronary lumen volume to left ventricle mass ratio with myocardial blood flow and fractional flow reserve.

BACKGROUND: A diminished coronary lumen volume to left ventricle mass ratio (V/M) derived from coronary computed tomography angiography (CCTA) has been proposed as factor contributing to impaired myocardial blood flow (MBF) even in the absence of obstructive disease on invasive coronary angiography (ICA). METHODS: Patients underwent CCTA, and positron emission tomography (PET) prior to ICA. Matched global V/M, global, and vessel specific hyperaemic MBF (hMBF), coronary flow reserve (CFR), and, FFR were available for 431 vessels in 152 patients. The median V/M (20.71 mm3/g) was used to divide the population into patients with either a low V/M or a high V/M. RESULTS: Overall, a higher percentage of vessels with an abnormal hMBF and FFR (34% vs. 19%, p = 0.009 and 20% vs. 9%, p = 0.004), as well as a lower FFR (0.93 [interquartile range: 0.85-0.97] vs. 0.95 [0.89-0.98], p = 0.016) values were observed in the low V/M group. V/M was weakly associated with vessel specific hMBF (R = 0.148, p = 0.027), and FFR (R = 0.156, p < 0.001). Among vessels with non-obstructive CAD on ICA (361 vessels), no association between V/M and vessel specific hMBF nor CFR was noted. However, in the absence of obstructive CAD, V/M was associated with (R = 0.081, p = 0.027), and independently predictive for FFR (p = 0.047). CONCLUSION: Overall, an abnormal vessel specific hMBF and FFR were more prevalent in patients with a low V/M compared to those with a high V/M. Furthermore, V/M was weakly associated with vessel specific hMBF and FFR. In the absence of obstructive CAD on ICA, V/M was weakly associated with notwithstanding independently predictive for FFR.

Low Dietary Protein Intakes and Associated Dietary Patterns and Functional Limitations in an Aging Population: A NHANES analysis.

OBJECTIVE: To investigate protein intakes across demographic characteristics in relation to dietary patterns and functional outcomes in older adults. DESIGN: Observational and cross-sectional study. SETTING: Non-institutionalized participants from the 2005-2014 National Health and Nutrition Examination Survey. PARTICIPANTS: Data from 11,680 adults were categorized into 51-60 years (n= 4,016), 61-70 years (n=3,854), and 71 years and older (n=3,810) for analysis. MEASUREMENTS: Adults were stratified by meeting or not meeting the protein recommendation (0.8 g/kg/d) to compare demographics, diet quality with Healthy Eating Index-2015, functional limitations, and other dietary intakes. Dietary recalls were collected using the multiple pass method. Data analyses were weighted to create a nationally-representative sample. RESULTS: Dietary protein intakes were significantly lower in older age groups, with up to 46% of the oldest adults not meeting the protein intake recommendation. Participants consuming protein below the recommended intake level had significantly poorer diet quality across all age groups (P<0.01), however, overall diet quality was better in older adults. Those not meeting the protein recommendation were more likely to have intakes of other nutrients below recommended levels. Those below the protein recommendation had significantly more functional limitations across all age groups, while grip strength was significantly lower in those over 70 years old. CONCLUSION: Lower protein intakes, and lower diet quality and physical functioning are related in an aging population. Meeting the protein recommendation was linked to better overall diet quality and may be protective of lean mass; therefore, evaluation of individual characteristics which may affect protein intakes is crucial in supporting older adults to meet their protein needs.

Beliefs and ideologies linked with approval of corporal punishment: a content analysis of online comments.

This study employs a novel strategy for identifying points of resistance to education efforts aimed at reducing rates of child physical abuse and use of corporal punishment (CP). We analyzed online comments (n = 581) generated in response to media coverage of a study linking CP with increased child aggression. Most comments (71%) reflected approval of hitting children for disciplinary purposes. Reasons for this approval were rooted in beliefs linking the use of CP with positive or neutral outcomes such as: 'I was spanked and I am okay', spanking improves child behavior, spanking is more effective than other forms of discipline and spanking is not abuse. However, also linked with approval were more macro-ideological beliefs about society such as: today's generation is worse off than previous ones, outside interference with parenting is wrong, one cause leads to an outcome, justifications for hitting children rooted in religious doctrine, bad parents cannot control their children and children have too much power. Our results suggest a need to better translate and disseminate empirical findings regarding the negative effects of CP to the public in a way that is highly sensitive to parents' needs to feel in control and effective when parenting.

Are the UK systems of innovation and evaluation of medical devices compatible? The role of NICE's Medical Technologies Evaluation Programme (MTEP).

The economic evaluation of medical products and services is increasingly prioritised by healthcare decision makers and plays a key role in informing funding allocation decisions. It is well known that there are a number of methodological difficulties in the health technology assessment of medical devices, particularly in the provision of efficacy evidence. By contrasting devices with pharmaceuticals, the way in which the differing systems of innovation mould the UK's industry landscape is described and substantiated with market statistics. In recognition of the challenges faced by industry, as well as the growing need for cost-effective allocation of National Health Service (NHS) resources, the National Institute for Health and Care Excellence (NICE) led the development of the Medical Technologies Evaluation Programme (MTEP), which launched in 2009/2010. The review of the UK's medical devices market supports the programme's three principal aims: to simplify access to evaluation, speed up the process, and increase evaluative capacity for devices within NICE. However, an analysis of the output of MTEP's first 3 years suggests that it has some way to go to meet each of these aims.

Sequential identification of boundary support parameters in a fluid-structure vascular model using patient image data.

Viscoelastic support has been previously established as a valuable modeling ingredient to represent the effect of surrounding tissues and organs in a fluid-structure vascular model. In this paper, we propose a complete methodological chain for the identification of the corresponding boundary support parameters, using patient image data. We consider distance maps of model to image contours as the discrepancy driving the data assimilation approach, which then relies on a combination of (1) state estimation based on the so-called SDF filtering method, designed within the realm of Luenberger observers and well adapted to handling measurements provided by image sequences, and (2) parameter estimation based on a reduced-order UKF filtering method which has no need for tangent operator computations and features natural parallelism to a high degree. Implementation issues are discussed, and we show that the resulting computational effectiveness of the complete estimation chain is comparable to that of a direct simulation. Furthermore, we demonstrate the use of this framework in a realistic application case involving hemodynamics in the thoracic aorta. The estimation of the boundary support parameters proves successful, in particular in that direct modeling simulations based on the estimated parameters are more accurate than with a previous manual expert calibration. This paves the way for complete patient-specific fluid-structure vascular modeling in which all types of available measurements could be used to estimate additional uncertain parameters of biophysical and clinical relevance.

External tissue support and fluid-structure simulation in blood flows.

The objective of this work is to address the formulation of an adequate model of the external tissue environment when studying a portion of the arterial tree with fluid-structure interaction. Whereas much work has already been accomplished concerning flow and pressure boundary conditions associated with truncations in the fluid domain, very few studies take into account the tissues surrounding the region of interest to derive adequate boundary conditions for the solid domain. In this paper, we propose to model the effect of external tissues by introducing viscoelastic support conditions along the artery wall, with two-possibly distributed-parameters that can be adjusted to mimic the response of various physiological tissues. In order to illustrate the versatility and effectiveness of our approach, we apply this strategy to perform patient-specific modeling of thoracic aortae based on clinical data, in two different cases and using a distinct fluid-structure interaction methodology for each, namely an Arbitrary Lagrangian-Eulerian (ALE) approach with prescribed inlet motion in the first case and the coupled momentum method in the second case. In both cases, the resulting simulations are quantitatively assessed by detailed comparisons with dynamic image sequences, and the model results are shown to be in very good adequacy with the data.

Three-dimensional simulations in Glenn patients: clinically based boundary conditions, hemodynamic results and sensitivity to input data.

While many congenital heart defects can be treated without significant long term sequelae, some achieve successful palliation as their definitive endpoints. The single-ventricle defect is one such defect and leaves the child with only one operational ventricle, requiring the systemic and the pulmonary circulations to be placed in series through several operations performed during early childhood. Numerical simulations may be used to investigate these hemodynamic conditions and their relation to post-operative sequelae; however, they rely heavily on boundary condition prescription. In this study, we investigate the impact of hemodynamic input data uncertainties on simulation results. Imaged-based patient-specific models of the multi-branched pulmonary arteries and superior vena cava were built for five cavopulmonary connection (i.e. Glenn) patients. Magnetic resonance imaging and catheterization data were acquired for each patient prior to their Fontan surgery. Inflow and outflow boundary conditions were constructed to match available clinical data and resulted in the development of a framework to incorporate these types of clinical data into patient-specific simulations. Three-dimensional computational fluid dynamics simulations were run and hemodynamic indicators were computed. Power loss was low (and efficiency very high) and a linear correlation was found between power loss and cardiac index among the five patients. Other indicators such as low wall shear stress were considered to better characterize these patients. Flow was complex and oscillatory near the anastomosis, and laminar in the smaller branches. While common trends were seen among patients, results showed differences among patients, especially in the 3D maps, strengthening the importance of patient-specific simulations. A sensitivity analysis was performed to investigate the impact of input data (clinical and modeling) to construct boundary conditions on several indicators. Overall, the sensitivity of the output indicators to the input data was small but non-negligible. The sensitivity of commonly used hemodynamic indicators to compare patients is discussed in this context. Power efficiency was much more sensitive to pressure variation than power loss. To increase the precision of such indicators, mean flow split between right and left lungs needs to be measured with more accuracy with higher priority than refining the model of how the flow is distributed on average among the smaller branches. Although ± 10% flow split imprecision seemed reasonable in terms of patient comparison, this study suggests that the common practice of imposing a right pulmonary artery/left pulmonary artery flow split of 55%/45% when performing patient specific simulations should be avoided. This study constitutes a first step towards understanding the hemodynamic differences between pre- and post Fontan surgery, predicting these differences, and evaluating surgical outcomes based on preoperative data.

Patient-specific modeling of blood flow and pressure in human coronary arteries.

Coronary flow is different from the flow in other parts of the arterial system because it is influenced by the contraction and relaxation of the heart. To model coronary flow realistically, the compressive force of the heart acting on the coronary vessels needs to be included. In this study, we developed a method that predicts coronary flow and pressure of three-dimensional epicardial coronary arteries by considering models of the heart and arterial system and the interactions between the two models. For each coronary outlet, a lumped parameter coronary vascular bed model was assigned to represent the impedance of the downstream coronary vascular networks absent in the computational domain. The intramyocardial pressure was represented with either the left or right ventricular pressure depending on the location of the coronary arteries. The left and right ventricular pressure were solved from the lumped parameter heart models coupled to a closed loop system comprising a three-dimensional model of the aorta, three-element Windkessel models of the rest of the systemic circulation and the pulmonary circulation, and lumped parameter models for the left and right sides of the heart. The computed coronary flow and pressure and the aortic flow and pressure waveforms were realistic as compared to literature data.

Pharmacokinetic differences in exposure to camphor after intraruminal dosing in selectively bred lines of goats.

A pharmacokinetic dosing study with camphor was used to determine whether selection lines of high-juniper-consuming goats (HJC, n = 12) and low-juniper-consuming goats (LJC, n = 12) differed in their respective disposition kinetics. Postdosing plasma camphor concentrations were used to examine whether a timed single blood sample collected after intraruminal administration of camphor would be a useful screening test to aid in the identification of HJC. Yearling female Boer x Spanish goats (n = 24) received a single intraruminal dose of monoterpene cocktail (0.270 g/kg of BW) containing 4 different monoterpenes that represented their composition previously reported for Ashe juniper (Juniperus ashei). Camphor, the predominant monoterpene in Ashe juniper, was 49.6% of the mix and was the monoterpene analyzed for this study. Blood samples were taken at 15 time points from 0 to 8 h after dosing. Concentrations of camphor were measured in plasma using solid phase extraction and gas chromatography/flame-ionization detection analysis. Maximal plasma concentration of camphor was greater for LJC than HJC (P = 0.01), and area under the curve extrapolated to infinity was greater for LJC than HJC (P < 0.01). Total systemic exposure (area under the curve) to camphor was 5 times less in HJC goats. We conclude that 1) HJC goats possess internal mechanisms to reduce the bioavailability of camphor, and 2) a blood sample taken at 45 min or at 60 min after intraruminal administration of camphor may be useful for identifying HJC individual animals from within large populations of goats.

Incorporating autoregulatory mechanisms of the cardiovascular system in three-dimensional finite element models of arterial blood flow.

The cardiovascular system is a closed-loop system in which billions of vessels interact with each other, and it enables the control of the systemic arterial pressure and varying organ flow through autoregulatory mechanisms. In this study, we describe the development of mathematical models of autoregulatory mechanisms for systemic arterial pressure and coronary flow and discuss the connection of these models to a hybrid numerical/analytic closed-loop model of the cardiovascular system. The closed-loop model consists of two lumped parameter heart models representing the left and right sides of the heart, a three-dimensional finite element model of the aorta with coronary arteries, three-element Windkessel models and lumped parameter coronary vascular models that represent the systemic circulation, and a three-element Windkessel model to approximate the pulmonary circulation. Using the connection between the systemic arterial pressure and coronary flow regulation systems, and the hybrid closed-loop model, we studied how the heart, coronary vascular beds, and arterial system respond to physiologic changes during light exercise and showed that these models can realistically simulate temporal behaviors of the heart, coronary vascular beds, and arterial system during exercise of healthy subjects. These models can be used to study temporal changes occurring in the heart, coronary vascular beds, and arterial system during cardiovascular intervention or changes in physiological states.

Outflow boundary conditions for 3D simulations of non-periodic blood flow and pressure fields in deformable arteries.

The simulation of blood flow and pressure in arteries requires outflow boundary conditions that incorporate models of downstream domains. We previously described a coupled multidomain method to couple analytical models of the downstream domains with 3D numerical models of the upstream vasculature. This prior work either included pure resistance boundary conditions or impedance boundary conditions based on assumed periodicity of the solution. However, flow and pressure in arteries are not necessarily periodic in time due to heart rate variability, respiration, complex transitional flow or acute physiological changes. We present herein an approach for prescribing lumped parameter outflow boundary conditions that accommodate transient phenomena. We have applied this method to compute haemodynamic quantities in different physiologically relevant cardiovascular models, including patient-specific examples, to study non-periodic flow phenomena often observed in normal subjects and in patients with acquired or congenital cardiovascular disease. The relevance of using boundary conditions that accommodate transient phenomena compared with boundary conditions that assume periodicity of the solution is discussed.

On coupling a lumped parameter heart model and a three-dimensional finite element aorta model.

Aortic flow and pressure result from the interactions between the heart and arterial system. In this work, we considered these interactions by utilizing a lumped parameter heart model as an inflow boundary condition for three-dimensional finite element simulations of aortic blood flow and vessel wall dynamics. The ventricular pressure-volume behavior of the lumped parameter heart model is approximated using a time varying elastance function scaled from a normalized elastance function. When the aortic valve is open, the coupled multidomain method is used to strongly couple the lumped parameter heart model and three-dimensional arterial models and compute ventricular volume, ventricular pressure, aortic flow, and aortic pressure. The shape of the velocity profiles of the inlet boundary and the outlet boundaries that experience retrograde flow are constrained to achieve a robust algorithm. When the aortic valve is closed, the inflow boundary condition is switched to a zero velocity Dirichlet condition. With this method, we obtain physiologically realistic aortic flow and pressure waveforms. We demonstrate this method in a patient-specific model of a normal human thoracic aorta under rest and exercise conditions and an aortic coarctation model under pre- and post-interventions.

Patient-specific modeling of cardiovascular mechanics.

Advances in numerical methods and three-dimensional imaging techniques have enabled the quantification of cardiovascular mechanics in subject-specific anatomic and physiologic models. Patient-specific models are being used to guide cell culture and animal experiments and test hypotheses related to the role of biomechanical factors in vascular diseases. Furthermore, biomechanical models based on noninvasive medical imaging could provide invaluable data on the in vivo service environment where cardiovascular devices are employed and on the effect of the devices on physiologic function. Finally, patient-specific modeling has enabled an entirely new application of cardiovascular mechanics, namely predicting outcomes of alternate therapeutic interventions for individual patients. We review methods to create anatomic and physiologic models, obtain properties, assign boundary conditions, and solve the equations governing blood flow and vessel wall dynamics. Applications of patient-specific models of cardiovascular mechanics are presented, followed by a discussion of the challenges and opportunities that lie ahead.

Heritability of juniper consumption in goats.

Data from goats (n = 505), collected over a 4-yr period, were used to estimate the heritability of juniper consumption. Juniper consumption was determined by near-infrared spectroscopy on fecal samples (n = 1,080) collected from female Boer-cross goats grazing pastures with a variety of plants, including juniper. The animals with records were progeny of 72 sires. Individual goats had from 1 to 4 observations over a 4-yr period. Predicted juniper consumption for individual observations ranged from -5 to +62% of the diet. Data were analyzed with a mixed model that included management group as a fixed effect, BW as a covariate, and permanent environment, animal, and residual as random effects. Management group was a significant source of variation. Least squares means of juniper consumption, as a percentage of the total intake, for management groups varied from 19 to 47%. Heritability of juniper consumption was 13%. Repeatability of juniper consumption was 31%. These results suggest that progress to selection for goats that will consume greater amounts of juniper is obtainable, but is expected to be slow.

Open Problems in Computational Vascular Biomechanics: Hemodynamics and Arterial Wall Mechanics.

The vasculature consists of a complex network of vessels ranging from large arteries to arterioles, capillaries, venules, and veins. This network is vital for the supply of oxygen and nutrients to tissues and the removal of carbon dioxide and waste products from tissues. Because of its primary role as a pressure-driven chemomechanical transport system, it should not be surprising that mechanics plays a vital role in the development and maintenance of the normal vasculature as well as in the progression and treatment of vascular disease. This review highlights some past successes of vascular biomechanics, but emphasizes the need for research that synthesizes complementary advances in molecular biology, biomechanics, medical imaging, computational methods, and computing power for purposes of increasing our understanding of vascular physiology and pathophysiology as well as improving the design of medical devices and clinical interventions, including surgical procedures. That is, computational mechanics has great promise to contribute to the continued improvement of vascular health.

Intracranial and abdominal aortic aneurysms: similarities, differences, and need for a new class of computational models.

Intracranial saccular and abdominal aortic aneurysms (ISAs and AAAs, respectively) result from different underlying disease processes and exhibit different rupture potentials, yet they share many histopathological and biomechanical characteristics. Moreover, as in other vascular diseases, hemodynamics and wall mechanics play important roles in the natural history and possible treatment of these two types of lesions. The goals of this review are twofold: first, to contrast the biology and mechanics of intracranial and abdominal aortic aneurysms to emphasize that separate advances in our understanding of each disease can aid in our understanding of the other disease, and second, to suggest that research on the biomechanics of aneurysms must embrace a new paradigm for analysis. That is, past biomechanical studies have provided tremendous insight but have progressed along separate lines, focusing on either the hemodynamics or the wall mechanics. We submit that there is a pressing need to couple in a new way the separate advances in vascular biology, medical imaging, and computational biofluid and biosolid mechanics to understand better the mechanobiology, pathophysiology, and treatment of these lesions, which continue to be responsible for significant morbidity and mortality. We refer to this needed new class of computational tools as fluid-solid-growth (FSG) models.