Iterative oxidation by TET1 is required for reprogramming of imprinting control regions and patterning of mouse sperm hypomethylated regions.

Ten-eleven translocation (TET) enzymes iteratively oxidize 5-methylcytosine (5mC) to generate 5-hydroxymethylcytosine (5hmC), 5-formylcytosine, and 5-carboxylcytosine to facilitate active genome demethylation. Whether these bases are required to promote replication-coupled dilution or activate base excision repair during mammalian germline reprogramming remains unresolved due to the inability to decouple TET activities. Here, we generated two mouse lines expressing catalytically inactive TET1 (Tet1-HxD) and TET1 that stalls oxidation at 5hmC (Tet1-V). Tet1 knockout and catalytic mutant primordial germ cells (PGCs) fail to erase methylation at select imprinting control regions and promoters of meiosis-associated genes, validating the requirement for the iterative oxidation of 5mC for complete germline reprogramming. TET1V and TET1HxD rescue most hypermethylation of Tet1-/- sperm, suggesting the role of TET1 beyond its oxidative capability. We additionally identify a broader class of hypermethylated regions in Tet1 mutant mouse sperm that depend on TET oxidation for reprogramming. Our study demonstrates the link between TET1-mediated germline reprogramming and sperm methylome patterning.

Prevalence of H. pylori and gastric intestinal metaplasia in BRCA1 and BRCA2 carriers.

BRCA1 and BRCA2 carriers may be at increased risk for gastric cancer (GC), however the mechanisms of gastric carcinogenesis remain poorly understood. We sought to determine the prevalence of GC risk factors Helicobacter pylori (H. pylori) infection and gastric intestinal metaplasia (GIM) among BRCA1/2 carriers to gain insight into the pathogenesis of GC in this population. 100 unselected BRCA1/2 carriers undergoing endoscopic ultrasound from 3/2022-3/2023 underwent concomitant upper endoscopy with non-targeted gastric antrum and body biopsies. The study population (70% women; mean age: 60.1) included 66% BRCA2 carriers. H. pylori was detected in one (1%) individual, 7 (7%) had GIM, 2 (2%) had autoimmune atrophic gastritis, and no GCs were diagnosed. Among BRCA1/2 carriers, H. pylori prevalence was low and GIM prevalence was similar to the general population, however identification of H. pylori or GIM may help inform future GC risk management strategies in BRCA1/2 carriers.

Essential and virulence-related protein interactions of pathogens revealed through deep learning.

Identification of bacterial protein-protein interactions and predicting the structures of the complexes could aid in the understanding of pathogenicity mechanisms and developing treatments for infectious diseases. Here, we developed a deep learning-based pipeline that leverages residue-residue coevolution and protein structure prediction to systematically identify and structurally characterize protein-protein interactions at the proteome-wide scale. Using this pipeline, we searched through 78 million pairs of proteins across 19 human bacterial pathogens and identified 1923 confidently predicted complexes involving essential genes and 256 involving virulence factors. Many of these complexes were not previously known; we experimentally tested 12 such predictions, and half of them were validated. The predicted interactions span core metabolic and virulence pathways ranging from post-transcriptional modification to acid neutralization to outer membrane machinery and should contribute to our understanding of the biology of these important pathogens and the design of drugs to combat them.

Extreme ultraviolet time-resolved photoelectron spectroscopy of adenine, adenosine and adenosine monophosphate in a liquid flat jet.

Time-resolved photoelectron spectroscopy using an extreme-ultraviolet (XUV) probe pulse was used to investigate the UV photoinduced dynamics of adenine (Ade), adenosine (Ado), and adenosine-5-monophosphate (AMP) in a liquid water jet. In contrast to previous studies using UV probe pulses, the XUV pulse at 21.7 eV can photoionize all excited states of a molecule, allowing for full relaxation pathways to be addressed after excitation at 4.66 eV. This work was carried out using a gas-dynamic flat liquid jet, resulting in considerably enhanced signal compared to a cylindrical jet. All three species decay on multiple time scales that are assigned based on their decay associated spectra; the fastest decay of ∼100 fs is assigned to ππ* decay to the ground state, while a smaller component with a lifetime of ∼500 fs is attributed to the nπ* state. An additional slower channel in Ade is assigned to the 7H Ade conformer, as seen previously. This work demonstrates the capability of XUV-TRPES to disentangle non-adiabatic dynamics in an aqueous solution in a state-specific manner and represents the first identification of the nπ* state in the relaxation dynamics of adenine and its derivatives.

Long-Term Ultrasound Twinkling Detectability and Safety of a Polymethyl Methacrylate Soft Tissue Marker Compared to Conventional Breast Biopsy Markers-A Preclinical Study in a Porcine Model.

OBJECTIVE: We have studied the use of polymethyl methacrylate (PMMA) as an alternative biopsy marker that is readily detectable with ultrasound Doppler twinkling in cases of in vitro, ex vivo, or limited duration in vivo settings. This study investigates the long-term safety and ultrasound Doppler twinkling detectability of a PMMA breast biopsy marker following local perturbations and different dwell times in a 6-mo animal experiment. METHODS: This study, which was approved by our Institutional Animal Care and Use Committee, involved three pigs and utilized various markers, including PMMA (Zimmer Biomet), 3D-printed, and Tumark Q markers. Markers were implanted at different times for each pig. Mesh material or ethanol was used to induce a local inflammatory reaction near certain markers. A semiquantitative twinkling score assessed twinkling for actionable localization during monthly ultrasounds. At the primary endpoint, ultrasound-guided localization of lymph nodes with detectable markers was performed. Following surgical resection of the localized nodes, histomorphometric analysis was conducted to evaluate for tissue ingrowth and the formation of a tissue rind around the markers. RESULTS: No adverse events occurred. Twinkling scores of all markers for all three pigs decreased gradually over time. The Q marker exhibited the highest mean twinkling score followed by the PMMA marker, PMMA with mesh, and Q with ethanol. The 3D-printed marker with mesh and PMMA with ethanol had the lowest scores. All wire-localized lymph nodes were successfully resected. Despite varying percentages of tissue rind around the markers and a significant reduction in overall twinkling (p < 0.001) over time, mean PMMA twinkling scores remained clinically actionable at 6 and 5 mo using a General Electric C1-6 probe and 9L-probe, respectively. CONCLUSIONS: In this porcine model, the PMMA marker demonstrates an acceptable safety profile. Clinically actionable twinkling aids PMMA marker detection even after 6 mo of dwell time in porcine lymph nodes. The Q marker maintained the greatest twinkling over time compared to all the other markers studied.

Is there evidence for factorial invariance of the COVID Stress Scales? an analysis of North American and cross-cultural populations.

The COVID-19 pandemic impacted the mental health of more citizens globally than any previous modern viral outbreak. In response to the psychological challenges associated with COVID-19, the COVID Stress Scales (CSS) were developed to assess the presence and severity of COVID-related distress. The initial North American validation study of the CSS identified that the scale comprised five factors: danger and contamination fears, fear of socioeconomic consequences, xenophobia, checking and reassurance seeking, and traumatic stress symptoms. The CSS have since been validated across a multitude of international populations. However, findings support a five- and six-factor model. Methodological issues make interpreting most studies supporting a five-factor model challenging. The purpose of this study was to re-evaluate the factor structure of the CSS using data from North American samples, to assess for potential factorial invariance, and compare these results to cross-cultural findings. Multiple confirmatory factor analyses (mCFA) were conducted across 28 different groups (e.g., age, ethnicity/race, sex) from two large independent North American samples from 2020 (n = 6827) and 2021 (n = 5787), assessing the fit indices of the five-, six-, and alternative-factor model of the CSS. The current results provide evidence for factorial invariance of the six-factor model of the CSS across different North American demographics and highlight potential challenges in interpreting the results of studies that have supported a five-factor model of the CSS.

Disruption of epithelium integrity by inflammation-associated fibroblasts through prostaglandin signaling.

Inflammation-associated fibroblasts (IAFs) are associated with progression and drug resistance of chronic inflammatory diseases such as inflammatory bowel disease (IBD), but their direct impact on epithelial cells is unknown. Here, we developed an in vitro model whereby human colon fibroblasts are induced by specific cytokines and recapitulate key features of IAFs in vivo. When cocultured with patient-derived colon organoids (colonoids), IAFs induced rapid colonoid expansion and barrier disruption due to swelling and rupture of individual epithelial cells. Colonoids cocultured with IAFs also show increased DNA damage, mitotic errors, and proliferation arrest. These IAF-induced epithelial defects are mediated by a paracrine pathway involving prostaglandin E2 and its receptor EP4, leading to protein kinase A -dependent activation of the cystic fibrosis transmembrane conductance regulator. EP4-specific chemical inhibitors effectively prevented IAF-induced colonoid swelling and restored normal proliferation and genome stability. These findings reveal a mechanism by which IAFs could promote and perpetuate IBD and suggest a therapeutic avenue to mitigate inflammation-associated epithelial injury.

Impact of SUSAN Denoising and ComBat Harmonization on Machine Learning Model Performance for Malignant Brain Neoplasms.

BACKGROUND AND PURPOSE: Feature variability in radiomics studies due to technical and magnet strength parameters is well known and may be addressed through various pre-processing methods. However, very few studies have evaluated downstream impact of variable pre-processing on model classification performance in a multi-class setting. We sought to evaluate the impact of SUSAN denoising and ComBat harmonization on model classification performance. MATERIALS AND METHODS: A total of 493 cases (410 internal and 83 external dataset) of glioblastoma (GB), intracranial metastatic disease (IMD) and primary CNS lymphoma (PCNSL) underwent semi-automated 3D-segmentation post baseline image processing (BIP) consisting of resampling, realignment, co-registration, skull stripping and image normalization. Post BIP, two sets were generated, one with and another without SUSAN denoising (SD). Radiomics features were extracted from both datasets and batch corrected to produce four datasets: (a) BIP, (b) BIP with SD, (c) BIP with ComBat and (d) BIP with both SD and ComBat harmonization. Performance was then summarized for models using a combination of six feature selection techniques and six machine learning models across four mask-sequence combinations with features derived from one-three (multi-parametric) MRI sequences. RESULTS: Most top performing models on the external test set used BIP+SD derived features. Overall, use of SD and ComBat harmonization led to a slight but generally consistent improvement in model performance on the external test set. CONCLUSIONS: The use of image pre-processing steps such as SD and ComBat harmonization may be more useful in a multiinstitutional setting and improve model generalizability. Models derived from only T1-CE images showed comparable performance to models derived from multiparametric MRI.

Excitability mediates allocation of pre-configured ensembles to a hippocampal engram supporting contextual conditioned threat in mice.

Little is understood about how engrams, sparse groups of neurons that store memories, are formed endogenously. Here, we combined calcium imaging, activity tagging, and optogenetics to examine the role of neuronal excitability and pre-existing functional connectivity on the allocation of mouse cornu ammonis area 1 (CA1) hippocampal neurons to an engram ensemble supporting a contextual threat memory. Engram neurons (high activity during recall or TRAP2-tagged during training) were more active than non-engram neurons 3 h (but not 24 h to 5 days) before training. Consistent with this, optogenetically inhibiting scFLARE2-tagged neurons active in homecage 3 h, but not 24 h, before conditioning disrupted memory retrieval, indicating that neurons with higher pre-training excitability were allocated to the engram. We also observed stable pre-configured functionally connected sub-ensembles of neurons whose activity cycled over days. Sub-ensembles that were more active before training were allocated to the engram, and their functional connectivity increased at training. Therefore, both neuronal excitability and pre-configured functional connectivity mediate allocation to an engram ensemble.

Control of feeding by a bottom-up midbrain-subthalamic pathway.

Investigative exploration and foraging leading to food consumption have vital importance, but are not well-understood. Since GABAergic inputs to the lateral and ventrolateral periaqueductal gray (l/vlPAG) control such behaviors, we dissected the role of vgat-expressing GABAergic l/vlPAG cells in exploration, foraging and hunting. Here, we show that in mice vgat l/vlPAG cells encode approach to food and consumption of both live prey and non-prey foods. The activity of these cells is necessary and sufficient for inducing food-seeking leading to subsequent consumption. Activation of vgat l/vlPAG cells produces exploratory foraging and compulsive eating without altering defensive behaviors. Moreover, l/vlPAG vgat cells are bidirectionally interconnected to several feeding, exploration and investigation nodes, including the zona incerta. Remarkably, the vgat l/vlPAG projection to the zona incerta bidirectionally controls approach towards food leading to consumption. These data indicate the PAG is not only a final downstream target of top-down exploration and foraging-related inputs, but that it also influences these behaviors through a bottom-up pathway.

Flood-irrigated agriculture mediates climate-induced wetland scarcity for summering sandhill cranes in western North America.

Information about species distributions is lacking in many regions of the world, forcing resource managers to answer complex ecological questions with incomplete data. Information gaps are compounded by climate change, driving ecological bottlenecks that can act as new demographic constraints on fauna. Here, we construct greater sandhill crane (Antigone canadensis tabida) summering range in western North America using movement data from 120 GPS-tagged individuals to determine how landscape composition shaped their distributions. Landscape variables developed from remotely sensed data were combined with bird locations to model distribution probabilities. Additionally, land-use and ownership were summarized within summer range as a measure of general bird use. Wetland variables identified as important predictors of bird distributions were evaluated in a post hoc analysis to measure long-term (1984-2022) effects of climate-driven surface water drying. Wetlands and associated agricultural practices accounted for 1.2% of summer range but were key predictors of occurrence. Bird distributions were structured by riparian floodplains that concentrated wetlands, and flood-irrigated agriculture in otherwise arid and semi-arid landscapes. Findings highlighted the role of private lands in greater sandhill crane ecology as they accounted for 78% of predicted distributions. Wetland drying observed in portions of the range from 1984 to 2022 represented an emerging ecological bottleneck that could limit future greater sandhill crane summer range. Study outcomes provide novel insight into the significance of ecosystem services provided by flood-irrigated agriculture that supported nearly 60% of wetland resources used by birds. Findings suggest greater sandhill cranes function as a surrogate species for agroecology and climate change adaptation strategies seeking to reduce agricultural water use through improved efficiency while also maintaining distinct flood-irrigation practices supporting greater sandhill cranes and other wetland-dependent wildlife. We make our wetland and sandhill crane summering distributions available as interactive web-based mapping tools to inform conservation design.

Altered DNA methylation underlies monocyte dysregulation and immune exhaustion memory in sepsis.

Monocytes can develop an exhausted memory state characterized by reduced differentiation, pathogenic inflammation, and immune suppression that drives immune dysregulation during sepsis. Chromatin alterations, notably via histone modifications, underlie innate immune memory, but the contribution of DNA methylation remains poorly understood. Using an ex vivo sepsis model, we show altered DNA methylation throughout the genome of exhausted monocytes, including genes implicated in immune dysregulation during sepsis and COVID-19 infection (e.g., Plac8). These changes are recapitulated in septic mice induced by cecal slurry injection. Methylation profiles developed in septic mice are maintained during ex vivo culture, supporting the involvement of DNA methylation in stable monocyte exhaustion memory. Methylome reprogramming is driven in part by Wnt signaling inhibition in exhausted monocytes and can be reversed with DNA methyltransferase inhibitors, Wnt agonists, or immune training molecules. Our study demonstrates the significance of altered DNA methylation in the maintenance of stable monocyte exhaustion memory.

Genetic parameters for carcass traits of progeny of beef bulls mated to dairy cows.

Beef × dairy crossbred cattle (n = 615) were used to evaluate the effect of preharvest indicator traits and genotypes on the accuracy of estimated breeding values (EBVs) of seedstock candidates for selection. Genotypes for 100,000 single nucleotide polymorphisms were provided by the American Simmental Association of purebred and crossbred seedstock animals (n = 2,632). Five hundred and ninety-five of the 615 beef × dairy cattle had carcass camera and ultrasound data. Phenotypes were not used for any of the seedstock animals even though some may have had performance and ultrasound data. We estimated the genomic relationship matrix among 3,247 animals including both phenotyped and unphenotyped animals. We computed genetic parameters among 37 traits using 666 bivariate restricted maximum likelihood analyses. The accuracy of EBV depends on heritability. For the sake of brevity, we report accuracy for marbling as a proxy for other traits with similar heritability. We focus on accuracy for marbling because marbling is the primary determinant of carcass value. We computed EBV for all 3,247 animals for marbling based on camera data postharvest using best linear unbiased prediction. We report evidence of overlap in causative genes among postharvest carcass traits; marbling, ribeye area, yield grade, fat thickness, and hot carcass weight (HCW) based on genetic correlations. Genetic correlations range from -0.73 to 0.89. Several live animal traits (frame size, body weight and ultrasound fat thickness and ribeye area) were genetically correlated with postharvest traits; including HCW, ribeye area, yield grade, fat thickness, and marbling. Genetic correlations between pre- and postharvest traits ranged from -0.53 to 0.95. Accuracy for marbling ranged from 0.64 to 0.80 for animals with marbling recorded, and from 0.09 to 0.60 for animals without marbling recorded. The accuracy of animals without phenotypes was related to the genomic relationship between animals with phenotype and those without. Live animal traits were useful for predicting economically important carcass traits based on genetic correlations. The accuracy of EBV for seedstock animals that were not phenotyped was low, but this is consistent with theory, and accuracy is expected to increase with the addition of genotypes and carcass data from beef × dairy animals.

Low-cost genotyping platforms and sexed-semen have enabled the production of high breeding value dairy replacement heifers from a fraction of the herd representing the most elite cows. The remainder of the cow herd can be bred to beef bulls using male-sexed-semen. Camera carcass data postharvest and ultrasound carcass estimates preharvest (live animals) on beef × dairy animals combined with genotypes and ultrasound on seedstock animals may provide an efficient scheme for selecting beef bulls to mate to dairy cows in the future to maximize carcass value of the progeny. Genotypes are needed to link carcass data from previously harvested to seedstock bull selection candidates because pedigree is typically not available for beef × dairy cattle. We report that live animal ultrasound carcass estimates are predictive of postharvest economically important carcass traits. The accuracy of genetic evaluation of selection candidates without recorded carcass traits was low but is expected to increase with more genotypes and phenotypes on beef × dairy cattle. Genotypes, ultrasound estimates, and camera carcass data on thousands of beef × dairy cattle could enable increased accuracy of selection with periodic infusion of new phenotypes from future generations.

An Engineered Laccase from Fomitiporia mediterranea Accelerates Lignocellulose Degradation.

Laccases from white-rot fungi catalyze lignin depolymerization, a critical first step to upgrading lignin to valuable biodiesel fuels and chemicals. In this study, a wildtype laccase from the basidiomycete Fomitiporia mediterranea (Fom_lac) and a variant engineered to have a carbohydrate-binding module (Fom_CBM) were studied for their ability to catalyze cleavage of ß-O-4' ether and C-C bonds in phenolic and non-phenolic lignin dimers using a nanostructure-initiator mass spectrometry-based assay. Fom_lac and Fom_CBM catalyze ß-O-4' ether and C-C bond breaking, with higher activity under acidic conditions (pH < 6). The potential of Fom_lac and Fom_CBM to enhance saccharification yields from untreated and ionic liquid pretreated pine was also investigated. Adding Fom_CBM to mixtures of cellulases and hemicellulases improved sugar yields by 140% on untreated pine and 32% on cholinium lysinate pretreated pine when compared to the inclusion of Fom_lac to the same mixtures. Adding either Fom_lac or Fom_CBM to mixtures of cellulases and hemicellulases effectively accelerates enzymatic hydrolysis, demonstrating its potential applications for lignocellulose valorization. We postulate that additional increases in sugar yields for the Fom_CBM enzyme mixtures were due to Fom_CBM being brought more proximal to lignin through binding to either cellulose or lignin itself.

Racial and ethnic disparities in psychological care for individuals with FASD: a dis/ability studies and critical race theory perspective toward improving prevention, assessment/diagnosis, and intervention.

Fetal alcohol spectrum disorders (FASD) are among the most common neurodevelopmental disorders and substantially impact public health. FASD can affect people of all races and ethnicities; however, there are important racial and ethnic disparities in alcohol-exposed pregnancy prevention, assessment and diagnosis of FASD, and interventions to support individuals with FASD and their families. In this article we use the Dis/Ability Studies and Critical Race Theory (Dis/Crit) framework to structure the exploration of disparities and possible solutions within these three areas (prevention, diagnosis, intervention). Dis/Crit provides a guide to understanding the intersection of dis/ability and race, while framing both as social constructs. Following the Dis/Crit framework, the systemic, historical, and contemporary racism and ableism present in psychological care is further discussed. We aim to elucidate these racial and ethnic disparities within the fields of psychology and neuropsychology through the Dis/Crit framework and provide potential points of action to reduce these disparities.

Streptolysin S is required for Streptococcus pyogenes nasopharyngeal and skin infection in HLA-transgenic mice.

Streptococcus pyogenes is a human-specific pathogen that commonly colonizes the upper respiratory tract and skin, causing a wide variety of diseases ranging from pharyngitis to necrotizing fasciitis and toxic shock syndrome. S. pyogenes has a repertoire of secreted virulence factors that promote infection and evasion of the host immune system including the cytolysins streptolysin O (SLO) and streptolysin S (SLS). S. pyogenes does not naturally infect the upper respiratory tract of mice although mice transgenic for MHC class II human leukocyte antigens (HLA) become highly susceptible. Here we used HLA-transgenic mice to assess the role of both SLO and SLS during both nasopharyngeal and skin infection. Using S. pyogenes MGAS8232 as a model strain, we found that an SLS-deficient strain exhibited a 100-fold reduction in bacterial recovery from the nasopharynx and a 10-fold reduction in bacterial burden in the skin, whereas an SLO-deficient strain did not exhibit any infection defects in these models. Furthermore, depletion of neutrophils significantly restored the bacterial burden of the SLS-deficient bacteria in skin, but not in the nasopharynx. In mice nasally infected with the wildtype S. pyogenes, there was a marked change in localization of the tight junction protein ZO-1 at the site of infection, demonstrating damage to the nasal epithelia that was absent in mice infected with the SLS-deficient strain. Overall, we conclude that SLS is required for the establishment of nasopharyngeal infection and skin infection in HLA-transgenic mice by S. pyogenes MGAS8232 and provide evidence that SLS contributes to nasopharyngeal infection through the localized destruction of nasal epithelia.

Engineering protein nanoparticles for drug delivery.

Protein nanoparticles offer a highly tunable platform for engineering multifunctional drug delivery vehicles that can improve drug efficacy and reduce off-target effects. While many protein nanoparticles have demonstrated the ability to tolerate genetic and posttranslational modifications for drug delivery applications, this review will focus on three protein nanoparticles of increasing size. Each protein nanoparticle possesses distinct properties such as highly tunable stability, capacity for splitting or fusing subunits for modular surface decoration, and well-characterized conformational changes with impressive capacity for large protein cargos. While many of the genetic and posttranslational modifications leverage these protein nanoparticle's properties, the shared techniques highlight engineering approaches that have been generalized across many protein nanoparticle platforms.

Epigenetic regulation of innate immune dynamics during inflammation.

Innate immune cells play essential roles in modulating both immune defense and inflammation by expressing a diverse array of cytokines and inflammatory mediators, phagocytizing pathogens to promote immune clearance, and assisting with the adaptive immune processes through antigen presentation. Rudimentary innate immune "memory" states such as training, tolerance, and exhaustion develop based on the nature, strength, and duration of immune challenge, thereby enabling dynamic transcriptional reprogramming to alter present and future cell behavior. Underlying transcriptional reprogramming are broad changes to the epigenome, or chromatin alterations above the level of DNA sequence. These changes include direct modification of DNA through cytosine methylation as well as indirect modifications through alterations to histones that comprise the protein core of nucleosomes. In this review, we will discuss recent advances in our understanding of how these epigenetic changes influence the dynamic behavior of the innate immune system during both acute and chronic inflammation, as well as how stable changes to the epigenome result in long-term alterations of innate cell behavior related to pathophysiology.

Improved Spatiotemporal Resolution in Echocardiography Using Mixed Geometry Imaging Sequences.

Cardiac ultrasound seeks to image the most dynamic environment in the body-the moving heart. Many modern ultrasound imaging techniques address the tradeoff between spatial and temporal resolution using either narrow focused beams or with broad beam, synthetic aperture (SA) sequences that have been shown to suffer from motion artifacts. Retrospective encoding for conventional ultrasound sequences (REFoCUS) unifies the processing of these various geometric sequences, but the motion sensitivity of this approach has yet to be investigated. We hypothesize that a "mixed sequence" enabled by the REFoCUS method incorporating several beam geometries may better resolve cardiac motion over a wide field of view (FOV) and at a high frame rate. First, the motion sensitivity of REFoCUS was evaluated in simulation for several focused and broad transmit profiles. Focused transmissions resolve both lateral and axial motion much more effectively than broad transmissions, with performance similar to conventional beamforming techniques. Second, a mixed sequence was designed that insonifies the full field-of-view with plane wave (PW) transmissions and key moving targets with focused transmissions. This mixed sequence was tested in simulation and in vivo and was used to image the heart as well as the liver, a low-motion control. By combining a sparse PW sequence ( n=60 ) with a small group of targeted focused transmissions ( n = 10), the anterior mitral valve leaflet (AML) at its peak observed velocity was better resolved. We believe that mixed sequences have strong potential to resolve cardiac motion at clinically relevant frame rates.

Development and validation of the Work Capital Scale.

Vocational psychologists have called for greater attention to different forms of capital, any resource or asset that confers profit and power, to better understand the vocational development process, particularly for those who lack resources and power. However, previous research has had several conceptual and measurement limitations, such as the use of less inclusive frameworks; a focus on more privileged populations; and the overuse of categorical, dummy coded, and objective measures. To address these limitations, the present study aimed to (a) develop an inclusive, subjective, continuous, and multidimensional work capital scale and (b) validate the new scale with representative samples of working adults and job seekers across two studies. We developed a 16-item four-factor Work Capital Scale that consists of Economic Work Capital, Human Work Capital, Social Work Capital, and Cultural Work Capital. Scores from the Work Capital Scale were invariant across household income, social class, gender, race, and employment status. We found that the correlational model fit best to the data and provided evidence for convergent and divergent validity by relating the subscales to subjective social class, objective socioeconomic indicators, and existing measures of capital. The present study advances theory and research in work capital and provides a tool for practitioners to use. (PsycInfo Database Record (c) 2024 APA, all rights reserved).