High throughput and rapid isolation of extracellular vesicles and exosomes with purity using size exclusion liquid chromatography.

Extracellular vesicles (EVs) have emerged as potential biomarkers for diagnosing a range of diseases without invasive procedures. Extracellular vesicles also offer advantages compared to synthetic vesicles for delivery of various drugs; however, limitations in segregating EVs from other particles and soluble proteins have led to inconsistent EV retrieval rates with low levels of purity. Here, we report a new high-yield (88.47 %) and rapid (<20 min) EV isolation method termed size exclusion - fast protein liquid chromatography (SE-FPLC). We show SE-FPLC can effectively isolate EVs from multiple sources including EVs derived from human and mouse cells and serum samples. The results indicate that SE-FPLC can successfully remove highly abundant protein contaminants such as albumin and lipoprotein complexes, which can represent a major hurdle in large scale isolation of EVs. The high-yield nature of SE-FPLC allows for easy industrial scaling up of EV production for various clinical utilities. SE-FPLC also enables analysis of small volumes of blood for use in point-of-care diagnostics in the clinic. Collectively, SE-FPLC offers many advantages over current EV isolation methods and offers rapid clinical translation.

Development of an engineered extracellular vesicles-based vaccine platform for combined delivery of mRNA and protein to induce functional immunity.

mRNA incorporated in lipid nanoparticles (LNPs) became a new class of vaccine modality for induction of immunity against COVID-19 and ushered in a new era in vaccine development. Here, we report a novel, easy-to-execute, and cost effective engineered extracellular vesicles (EVs)-based combined mRNA and protein vaccine platform (EVX-M+P vaccine) and explore its utility in proof-of-concept immunity studies in the settings of cancer and infectious disease. As a first example, we engineered EVs, natural nanoparticle carriers shed by all cells, to contain ovalbumin mRNA and protein (EVOvaM+P vaccine) to serve as cancer vaccine against ovalbumin-expressing melanoma tumors. EVOvaM+P administration to mice with established melanoma tumors resulted in tumor regression associated with effective humoral and adaptive immune responses. As a second example, we generated engineered EVs that contain Spike (S) mRNA and protein to serve as a combined mRNA and protein vaccine (EVSpikeM+P vaccine) against SARS-CoV-2 infection. EVSpikeM+P vaccine administration in mice and baboons elicited robust production of neutralizing IgG antibodies against RBD (receptor binding domain) of S protein and S protein specific T cell responses. Our proof-of-concept study describes a new platform with an ability for rapid development of combination mRNA and protein vaccines employing EVs for deployment against cancer and other diseases.

Adolescents with Elevated Psychopathic Traits are Associated with an Increased Risk for Premature Mortality.

The mortality rate among adolescents has been steadily increasing in recent years. Researchers have previously identified forms of externalizing psychopathology measured during adolescence associated with an increased risk for premature mortality, including attention-deficit/hyperactivity disorder (ADHD), substance use disorders (SUDs), oppositional defiant disorder (ODD), and conduct disorder (CD). The current study investigated whether additional personality traits (i.e., adolescent psychopathic traits, assessed via the Hare Psychopathy Checklist: Youth Version [PCL:YV]) were also associated with premature mortality risk among maximum-security incarcerated adolescents (N = 332). During a follow-up period ranging from 10 to 14 years, premature mortality was observed in n = 33 participants (9.94%), a mortality rate nearly ten times higher than population norms. We observed that adolescents scoring the highest on PCL:YV total scores exhibited significantly higher rates of premature mortality compared to adolescents scoring lower on PCL:YV total scores via Fisher's exact tests. Additionally, through univariate Cox proportional hazard regression analyses, PCL:YV total, Factor 2 (measuring lifestyle/behavioral and antisocial/developmental psychopathic traits), Facet 1 (measuring interpersonal psychopathic traits), and Facet 3 (measuring lifestyle/behavioral psychopathic traits) scores were associated with faster time to premature mortality. In supplemental analyses performed, we observed that adolescents meeting criteria for externalizing psychopathology (i.e., ADHD, SUDs, ODD, and CD) did not exhibit higher rates of premature mortality compared to control participants. The current study therefore identifies additional maladaptive personality traits to consider in relation to premature mortality risk (i.e., psychopathic traits) among a high-risk sample of incarcerated adolescents.

Psychopathic Traits in Adult versus Adolescent Males: Measurement Invariance across the PCL-R and PCL:YV.

Both the Psychopathy Checklist-Revised (PCL-R) and the Psychopathy Checklist: Youth Version (PCL:YV), respectively, are established instruments for assessment of psychopathy and development of psychopathic propensity. To reliably compare scores from both instruments, measurement invariance must be established. The current study involved a combined sample of 1091 male participants (adults = 813; adolescents = 278) from correctional facilities in New Mexico. An exploratory structural equation modeling (ESEM) framework was used to test for measurement invariance. The four-factor ESEM model demonstrated good fit for the combined and individual samples. Results from the multiple group ESEM provide evidence for generally strong invariance, with equivalent factor loadings and thresholds. Adolescents exhibited decreased latent interpersonal traits but increased latent features on other PCL factors (affective, lifestyle, and antisocial) compared to adults. Findings suggest that the four-factor model and the measurement of psychopathic traits remain consistent across age groups. Implications of the findings within research and clinical contexts are discussed.

Discordance between taxonomy and population genomic data: An avian example relevant to the United States Endangered Species Act.

Population genomics can reveal cryptic biological diversity that may impact fitness while simultaneously serving to delineate relevant conservation units. Here, we leverage the power of whole-genome resequencing for conservation by studying 433 individual lesser prairie-chicken (Tympanuchus pallidicinctus; LEPC, a federally endangered species of conservation concern in the United States) and greater prairie-chicken (Tympanuchus cupido; GRPC, a legally huntable species throughout much of its range). The genomic diversity of two formally recognized distinct population segments (DPSs) of LEPCs is similar, but they are genetically distinct. Neither DPS is depleted of its genomic diversity, neither is especially inbred, and temporal diversity is relatively stable in both conservation units. Interspecific differentiation between the two species was only slightly higher than that observed between LEPC DPSs, due largely to bidirectional introgression. The high resolution provided by our dataset identified a genomic continuum between the two species such that individuals sampled from the hybrid zone were imperfectly assigned to their presumptive species when considering only their physical characteristics. The admixture between the two species is reflected in the spectrum of individual ancestry coefficients, which has legal implications for the "take" of individuals under the Endangered Species Act. Overall, our data highlight the recurring dissonance between static policies and dynamic species boundaries that are increasingly obvious in the population genomic era.

Identification of genomic regions and genes associated with subclinical ketosis in periparturient dairy cows.

Subclinical ketosis (SCK) is a prevalent metabolic disorder that occurs during the transition to lactation period. It is defined as a high blood concentration of ketone bodies (beta-hydroxybutyric acid f ≥ 1.2 mmol/L) within the first few weeks of lactation, and often presents without clinical signs. SCK is mainly caused by negative energy balance (NEB). The objective of this study is to identify single nucleotide polymorphisms (SNPs) associated with SCK using genome-wide association studies (GWAS), and to predict the biological functions of proximal genes using gene-set enrichment analysis (GSEA). Blood samples were collected from 112 Holstein cows between 5 and 18 days postpartum to determine the incidence of SCK. Genomic DNA extracted from both SCK and healthy cows was examined using the Illumina Bovine SNP50K BeadChip for genotyping. GWAS revealed 194 putative SNPs and 163 genes associated with those SNPs. Additionally, GSEA showed that the genes retrieved by Database for Annotation, Visualization, and Integrated Discovery (DAVID) belonged to calcium signaling, starch and sucrose, immune network, and metabolic pathways. Furthermore, the proximal genes were found to be related to germ cell and early embryo development. In summary, this study proposes several feasible SNPs and genes associated with SCK through GWAS and GSEA. These candidates can be utilized in selective breeding programs to reduce the genetic risk for SCK and subfertility in high-performance dairy cows.

Midcareer Satisfaction and Likelihood of Leaving Current Position of Former Career Development Awardees.

This study assesses career satisfaction, discrepancies between ideal and expected careers, and likelihood of leaving current positions among former K awardees.

Burnout Among Mid-Career Academic Medical Faculty.

Importance: Studies reveal that most physicians report symptoms of burnout. Less is known about burnout in mid-career medical faculty specifically. Objective: To characterize burnout and its risk factors, particularly differences by gender, among mid-career medical faculty. Design, Setting, and Participants: Between August 2021 and August 2022, a survey was sent to 1430 individuals who received new National Institutes of Health K08 and K23 career development awards from 2006 to 2009. Data were analyzed between June and October 2023. Main Outcomes and Measures: Personal and work-related burnout as evaluated using the Copenhagen Burnout Inventory (CBI). The CBI score ranges from 0 to 100, with a score of 50 or higher indicating a high degree of burnout. Multivariable models were used to investigate associations between burnout and participant characteristics, including race and ethnicity, sexual orientation and gender identity, academic rank, work climate, experiences of workplace sexual harassment, sleep hours, work and domestic caregiving time, and time allocation changes in work and domestic work hours compared with before the COVID-19 pandemic. Work climate was evaluated by a general climate elements scale assessing elements such as friendliness, respect, and collegiality, and a diversity, equity, and inclusion climate elements scale assessing elements such as homogeneity, sexism, and homophobia; higher scores indicated a more favorable view of the climate. Results: In all, 1430 surveys were sent, 926 candidates responded (65% response rate), and the analytic cohort was limited to the 841 respondents who were still in academic medicine (50.7% men). Burnout was significantly more common for women than men (mean [SD] CBI personal scores, 46.6 [19.4] vs 37.5 [17.2]; P < .001; mean [SD] CBI work-related scores, 43.7 [20.4] vs 34.6 [19.7]; P < .001). In multivariable models, personal burnout was significantly more likely for women (adjusted odds ratio [AOR], 2.29 [95% CI, 1.54-3.41]; P < .001) and with more weekly hours of patient care (AOR, 1.07 [95% CI, 1.00-1.15] for each 5-hour increase; P = .04). Personal burnout was less likely with more nightly sleep hours (AOR, 0.68 [95% CI, 0.56-0.81] for each 1-hour increase; P < .001) and with an improved general work climate rating (AOR, 0.64 [95% CI, 0.48-0.85] for each 1-point increase in general work climate scale score; P = .002). Work-related burnout was also significantly more likely for women than men (AOR, 1.77 [95% CI, 1.17-2.69]; P = .007). Greater work-related burnout was associated with an increase of 8 or more work hours per week compared with before the COVID-19 pandemic (AOR, 1.87 [95% CI, 1.13-3.08]; P = .01), more weekly hours of patient care (AOR, 1.11 [95% CI, 1.03-1.19] for each 5-hour increase; P = .007), and a workplace sexual harassment experience in the past 2 years (AOR, 1.71 [95% CI, 1.11-2.62]; P = .01). Work-related burnout was significantly less likely with more nightly sleep hours (AOR, 0.80 [95% CI, 0.66-0.96] for each 1-hour increase; P = .02) and with an improved general work climate rating (AOR, 0.49; [95% CI, 0.36-0.65] for each 1-point increase in general work climate scale score; P < .001). Conclusions and Relevance: This survey study of K grant awardees revealed substantial rates of burnout among mid-career medical faculty, and burnout rates differed by gender. Evidence-based interventions are needed to realize the benefits of workforce diversity and vitality.

Genetic relationships between behavioral traits and feed efficiency traits in lactating Holstein cows.

The evaluation of dairy cow feed efficiency using residual feed intake accounts for known energy sinks. However, behavioral traits may also contribute to the variation in feed efficiency. Our objective was to estimate the heritability and repeatability of behavioral traits and their genetic correlations with feed efficiency and its components in lactating Holstein cows. The first dataset consisted of 36,075 daily rumination and lying time records collected using a SMARTBOW ear-tag accelerometer (Zoetis, Parsippany, NJ) and 6,371 weekly feed efficiency records of 728 cows from the University of Wisconsin-Madison. The second dataset consisted of 59,155 daily activity records, measured as number of steps, recorded by pedometers (AfiAct; SAE Afikim, Kibbutz Afikim, Israel) and 8,626 weekly feed efficiency records of 635 cows from the University of Florida. Feed efficiency and its components included DMI, change in BW, metabolic BW, secreted milk energy, and residual feed intake. The statistical models included the fixed effect of cohort, lactation number, and days in milk, and the random effects of animal and permanent environment. Heritability estimates for behavioral traits using daily records were 0.19 ± 0.06 for rumination and activity, and 0.37 ± 0.07 for lying time. Repeatability estimates for behavioral traits using daily data ranged from 0.56 ± 0.02 for activity to 0.62 ± 0.01 for lying time. Both heritability and repeatability estimates were larger when weekly records instead of daily records were used. Rumination and activity had positive genetic correlations with residual feed intake (0.40 ± 0.19 and 0.31 ± 0.22, respectively) and lying time had a negative genetic correlation with this residual feed intake (-0.27 ± 0.11). These results indicate that more efficient cows tend to spend more time lying and less time active. Additionally, less efficient cows tend to eat more and therefore also tend to ruminate longer. Overall, sensor-based behavioral traits are heritable and genetically correlated with feed efficiency and its components and, therefore, they could be used as indicators to identify feed-efficient cows within the herd.

Investigating relationships between the host genome, rumen microbiome, and dairy cow feed efficiency using mediation analysis with structural equation modeling.

The rumen microbiome is crucial for converting feed into absorbable nutrients used for milk synthesis, and the efficiency of this process directly affects the profitability and sustainability of the dairy industry. Recent studies have found that the rumen microbial composition explains part of the variation in feed efficiency traits, including dry matter intake, milk energy, and residual feed intake. The main goal of this study was to reveal relationships between the host genome, the rumen microbiome, and dairy cow feed efficiency using structural equation models. Our specific objectives were to (1) infer the mediation effects of the rumen microbiome on feed efficiency traits, (2) estimate the direct and total heritability of feed efficiency traits, and (3) calculate the direct and total breeding values of feed efficiency traits. Data consisted of dry matter intake, milk energy, and residual feed intake records, SNP genotype data, and 16S rRNA rumen microbial abundances from 448 mid-lactation Holstein cows from 2 research farms. We implemented structural equation models such that the host genome directly affects the phenotype (GP → P) and the rumen microbiome (GM → P), and the microbiome affects the phenotype (M → P), partially mediating the effect of the host genome on the phenotype (G → M → P). We found that 7% to 30% of microbes within the rumen microbial community had structural coefficients different from zero. We classified these microbes into 3 groups that could have different uses in dairy farming. Microbes with heritability <0.10 but significant causal effects on feed efficiency are attractive for external interventions. On the other hand, 2 groups of microbes with heritability ≥0.10, significant causal effects, and genetic covariances and causal effects with the same or opposite sign to feed efficiency are attractive for selective breeding, improving or decreasing the trait heritability and response to selection, respectively. In general, the inclusion of the different microbes in genomic models tends to decrease the trait heritability rather than increase it, ranging from -15% to +5% depending on the microbial group and phenotypic trait. Our findings provide more understanding to target rumen microbes that can be manipulated, either through selection or management interventions, in order to improve feed efficiency traits.

Association Between Traumatic Brain Injury and Psychopathic Traits Among Justice-Involved Adolescents.

Traumatic brain injury (TBI) is a global public health problem and is highly prevalent among justice-involved populations. Pediatric TBI is linked with long-term negative outcomes and is correlated with substance use, criminal behavior, psychiatric disorders, and disruptions in neurocognition. These same TBI correlates are evident among youth with psychopathic traits. Given ongoing neurobiological and social development in adolescence, understanding the link between psychopathic traits and TBI in justice-involved youth is critical. A sample of 263 male adolescents were recruited from a maximum-security juvenile justice facility. Using a structural equation modeling (SEM) framework, measurement invariance of psychopathic traits (TBI ±) was tested, and psychopathy scores were accounted for in terms of TBI variables (severity, age of first TBI, total number), participant's age, IQ, substance use, and internalizing psychopathology. There was evidence of strong invariance across TBI status and those with TBI had higher affective and impulsive lifestyle psychopathic traits than adolescents without TBI. The SEM indicated that TBI severity was associated with lower IQ scores, which in turn were associated with increased lifestyle/antisocial (Factor 2) psychopathic traits. Total number of TBIs was associated with higher substance use, which was associated with both increased interpersonal/affective (Factor 1) and Factor 2 psychopathic traits. These TBI variables also had indirect associations with psychopathic traits through IQ and substance use. The findings indicate that TBI is associated with psychopathic traits and suggest that disturbances in cognition and substance use may be treatment targets for youth with TBI and psychopathic traits.

Behavioral consistency of competitive behaviors and feeding patterns in lactating dairy cows across stocking densities at the feed bunk.

Introduction: High feed bunk stocking densities can differentially impact individual dairy cows' competitive behaviors, feeding patterns, and feed efficiency. Our objective was to manipulate feed bunk stocking densities to evaluate intra-individual behavioral consistency across stocking densities and quantify associations with feed efficiency and production. Methods: Thirty-two primiparous (130.7 ± 29.0 days in milk, DIM) and 32 multiparous (111.3 ± 38.3 DIM) lactating Holstein cows were housed with 32 roughage intake control (RIC) bins. Each cow was assigned to share 8 bins with others of the same parity and similar body weight (16 cows/block; 2:1 feed bunk stocking density except during tests). Competition and feeding patterns were evaluated via video and RIC data, respectively, at 3 stocking densities (1:1, 2:1, 4:1 cows/bin) during 1-h tests (2 tests/stocking density; 6 tests/cow) following 2 h feed deprivation. Residual feed intake (RFI) was calculated across the 45-d study as the difference between observed and predicted dry matter intake (DMI) after accounting for known energy sinks. Linear mixed models were used to evaluate the overall impact of test stocking density on competition and feeding patterns. To evaluate intra-individual consistency between stocking densities, individual stability statistic (ISS) scores were computed. Correlational relationships were determined between RFI and ISS scores. Results and dicsussion: Cows displayed the most competitive behaviors at 2:1 stocking density (p < 0.0001) but experienced the highest rate of contacts per minute of eating time at 4:1 (1:1 vs. 2:1 vs. 4:1: 0.09 vs. 0.95 vs. 1.60 contacts/min; p < 0.0001). Feeding patterns were modulated as stocking density increased; eating rate increased (0.16 vs. 0.18 vs. 0.22 kg/min; p < 0.001) as eating time (40.3 vs. 28.2 vs. 14.6 min; p < 0.001) and DMI decreased (6.3 vs. 5.1 vs. 3.0 kg; p < 0.001). As stocking density doubled, individuals remained consistent (p = 0.018) in time spent near others actively eating and tended to remain consistent in competition behavior and feeding patterns (0.053 ≤ p ≤ 0.094). Between 2:1 and 4:1, cows with higher DMI and milk production were more consistent in first-visit DMI and duration. Feed efficiency was not associated with behavioral consistency across the tests (p ≥ 0.14). Nonetheless, feed bunk stocking density has behavioral implications which should be considered in nutritional management decisions.

Striatal brain volume linked to severity of substance use in high-risk incarcerated youth.

Substance use disorders among juveniles are a major public health concern and are often intertwined with other psychosocial risk factors including antisocial behavior. Identifying etiological risks and mechanisms promoting substance use disorders remains a high priority for informing more focused interventions in high-risk populations. The present study examined brain gray matter structure in relation to substance use severity among n = 152 high-risk, incarcerated boys (aged 14-20). Substance use severity was positively associated with gray matter volume across several frontal/striatal brain regions including amygdala, pallidum, putamen, insula, and orbitofrontal cortex. Effects were apparent when using voxel-based-morphometric analysis, as well as in whole-brain, data-driven, network-based approaches (source-based morphometry). These findings support the hypothesis that elevated gray matter volume in striatal reward circuits may be an endogenous marker for vulnerability to severe substance use behaviors among youth.

Facial modeling and measurement based upon homologous topographical features.

Measurement of human faces is fundamental to many applications from recognition to genetic phenotyping. While anthropometric landmarks provide a conventional set of homologous measurement points, digital scans are increasingly used for facial measurement, despite the difficulties in establishing their homology. We introduce an alternative basis for facial measurement, which 1) provides a richer information density than discrete point measurements, 2) derives its homology from shared facial topography (ridges, folds, etc.), and 3) quantifies local morphological variation following the conventions and practices of anatomical description. A parametric model that permits matching a broad range of facial variation by the adjustment of 71 parameters is demonstrated by modeling a sample of 80 adult human faces. The surface of the parametric model can be adjusted to match each photogrammetric surface mesh generally to within 1 mm, demonstrating a novel and efficient means for facial shape encoding. We examine how well this scheme quantifies facial shape and variation with respect to geographic ancestry and sex. We compare this analysis with a more conventional, landmark-based geometric morphometric (GMM) study with 43 landmarks placed on the same set of scans. Our multivariate statistical analysis using the 71 attribute values separates geographic ancestry groups and sexes with a high degree of reliability, and these results are broadly similar to those from GMM, but with some key differences that we discuss. This approach is compared with conventional, non-parametric methods for the quantification of facial shape, including generality, information density, and the separation of size and shape. Potential uses for phenotypic and dysmorphology studies are also discussed.

Enantioselective Paternò-Büchi Reactions: Strategic Application of a Triplet Rebound Mechanism for Asymmetric Photocatalysis.

The Paternò-Büchi reaction is the [2 + 2] photocycloaddition of a carbonyl with an alkene to afford an oxetane. Enantioselective catalysis of this classical photoreaction, however, has proven to be a long-standing challenge. Many of the best-developed strategies for asymmetric photochemistry are not suitable to address this problem because the interaction of carbonyls with Brønsted or Lewis acidic catalysts can alter the electronic structure of their excited state and divert their reactivity toward alternate photoproducts. We show herein that a triplet rebound strategy enables the stereocontrolled reaction of an excited-state carbonyl compound in its native, unbound state. These studies have resulted in the development of the first highly enantioselective catalytic Paternò-Büchi reaction, catalyzed by a novel hydrogen-bonding chiral Ir photocatalyst.

Dry matter intake in US Holstein cows: Exploring the genomic and phenotypic impact of milk components and body weight composite.

Large datasets allow estimation of feed required for individual milk components or body maintenance. Phenotypic regressions are useful for nutrition management, but genetic regressions are more useful in breeding programs. Dry matter intake records from 8,513 lactations of 6,621 Holstein cows were predicted from phenotypes or genomic evaluations for milk components and body size traits. The mixed models also included DIM, age-parity subclass, trial date, management group, and BW change during 28- and 42-d feeding trials in mid lactation. Phenotypic regressions of DMI on milk (0.014 ± 0.006), fat (3.06 ± 0.01), and protein (4.79 ± 0.25) were much less than corresponding genomic regressions (0.08 ± 0.03, 11.30 ± 0.47, and 9.35 ± 0.87, respectively) or sire genomic regressions multiplied by 2 (0.048 ± 0.04, 6.73 ± 0.94, and 4.98 ± 1.75). Thus, marginal feed costs as fractions of marginal milk revenue were higher from genetic than phenotypic regressions. According to the ECM formula, fat production requires 69% more DMI than protein production. In the phenotypic regression, it was estimated that protein production requires 56% more DMI than fat. However, the genomic regression for the animal showed a difference of only 21% more DMI for protein compared with fat, whereas the sire genomic regressions indicated approximately 35% more DMI for fat than protein. Estimates of annual maintenance in kilograms DMI/kilograms BW per lactation were similar from phenotypic regression (5.9 ± 0.14), genomic regression (5.8 ± 0.31), and sire genomic regression multiplied by 2 (5.3 ± 0.55) and are larger than those estimated by the National Academies for Science, Engineering, and Medicine based on NEL equations. Multiple regressions on genomic evaluations for the 5 type traits in body weight composite (BWC) showed that strength was the type trait most associated with BW and DMI, agreeing with the current BWC formula, whereas other traits were less useful predictors, especially for DMI. The Net Merit formula used to weight different genetic traits to achieve an economically optimal overall selection response was revised in 2021 to better account for these estimated regressions. To improve profitability, breeding programs should select smaller cows with negative residual feed intake that produce more milk, fat, and protein.

Direct Probe of Vibrational Fingerprint and Combination Band Coupling.

Vibrational fingerprints and combination bands are a direct measure of couplings that control molecular properties. However, most combination bands possess small transition dipoles. Here we use multiple, ultrafast coherent infrared pulses to resolve vibrational coupling between CH3CN fingerprint modes at 918 and 1039 cm-1 and combination bands in the 2750-6100 cm-1 region via doubly vibrationally enhanced (DOVE) coherent multidimensional spectroscopy (CMDS). This approach provides a direct probe of vibrational coupling between fingerprint modes and near-infrared combination bands of large and small transition dipoles in a molecular system over a large frequency range.

National science foundation grant awardees' perspectives on Article X and sexual harassment in science.

Federal scientific agencies seek to make an impact on the continued prevalence of sexual harassment in the scientific academic community beyond institutional self-regulation. The National Science Foundation's Article X, released in 2018, is one of the most significant and ambitious federal policy initiatives to address sexual harassment. The present article presents the results of the first study to examine scientists' knowledge and attitudes about this important recent policy. We found, although overall knowledge about Article X was fairly low, the majority of participants responded positively to it. Crucially, impressions of the policy varied based on past experience and demographic factors. Individuals who had experienced harassment in the past year were less likely to believe the policy would help reduce sexual harassment in the sciences compared to those who had not experienced harassment (OR = 0.47, 95% CI:0.23-0.97, p = .034) and had greater odds of endorsing that the policy failed to go far enough (OR = 2.77, 95% CI:1.15-6.66, p = .023). Associations between demographic factors and views of the policy were less pronounced, but it is notable that, compared to their White counterparts, Black participants were more likely to believe the policy went too far (OR = 5.87, 95% CI:1.04-33.17, p = .045). Additionally, concerns were raised about the institutional enforcement of these policies and the existence of sufficient protections for survivors. Our work has implications for NSF's continued evaluation of the efficacy of this program as well as for other federal agencies implementing or considering similar policies.

Long-term growth, feed efficiency, enteric methane emission, and blood metabolite responses to in utero hyperthermia in Holstein heifers.

Dairy producers are experiencing production and animal welfare pressures from the increasing frequency and severity of heat stress events due to global climate change. Offspring performance during the preweaning and lactating periods is compromised when exposed to heat stress during late gestation (in utero). However, knowledge of the lingering effects of in utero heat stress on yearling dairy heifers is limited. Herein, we investigated the long-term effects of in utero heat stress on heifer growth, feed efficiency, and enteric methane emissions in postpubertal heifers. During the last 56 d of gestation, 38 pregnant cows carrying heifer calves were exposed to either heat stress (IUHT; n = 17) or artificial cooling (IUCL; n = 21). At 18 ± 1 mo of age, the resulting IUCL and IUHT heifers were enrolled in the present 63-d study. Heifers were blocked by weight and randomly assigned to 3 pens with Calan gates. Body weights were recorded on 3 consecutive days at the start and end of the trial and used to calculate ADG. Body condition score, hip width, body length, and chest girth were measured at the start and end of the study. All heifers were fed a TMR comprised of 46.6% oatlage, 44.6% grass/alfalfa haylage, 7.7% male-sterile corn silage, 0.3% urea, and 0.8% mineral/vitamin supplement (on a DM basis). The TMR and refusal samples were obtained daily, composited weekly, and dried to calculate DMI. During the study, each pen had access to a GreenFeed unit for 8 ± 1d to measure CH4 and CO2 gas fluxes. During the last 3 d of measuring CH4 and CO2 fluxes, fecal samples were collected, composited by animal, dried, and analyzed to calculate NDF, OM, and DM digestibility. On the last day of fecal sampling, blood samples were also collected via coccygeal venipuncture, and GC time-of-flight MS analysis was performed. Residual feed intake (RFI; predicted DMI - observed DMI), and feed conversion efficiency (FCE; DMI/ADG) were calculated to estimate feed efficiency. No differences were found in initial or final BW, hip width, chest girth, or BCS; however, IUCL heifers were longer in body length compared with IUHT heifers. Dry matter intake, ADG, RFI, and FCE were similar between IUHT and IUCL heifers. In utero heat-stressed and IUCL heifers produced similar amounts of CH4 and CO2, and no differences were found in the number of GreenFeed visits or latency to approach the GreenFeed. The concentrations of 6 blood metabolites involved in lipogenic pathways were different between in utero treatments. In conclusion, in utero heat stress does not seem to have long-term effects on feed efficiency or methane emissions during the postpubertal growing phase; however, IUCL heifers maintained a body-length advantage over their IUHT counterparts and differed in concentrations of several candidate metabolites that encourage further exploration of their potential function in key organs, such as the liver and mammary gland.