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Since SARS-CoV-2 emerged in late 2019, it spread from China to the rest of the world. An initial concern was the potential for vaccine- or antibody-dependent enhancement (ADE) of disease as had been reported with other coronaviruses. To evaluate this, we first developed a ferret model by exposing ferrets to SARS-CoV-2 by either mucosal inoculation (intranasal/oral/ocular) or inhalation using a small particle aerosol. Mucosal inoculation caused a mild fever and weight loss that resolved quickly; inoculation via either route resulted in virus shedding detected in the nares, throat, and rectum for 7-10 days post-infection. To evaluate the potential for ADE, we then inoculated groups of ferrets intravenously with 0.1, 0.5, or 1 mg/kg doses of a human polyclonal anti-SARS-CoV-2 IgG from hyper-immunized transchromosomic bovines (SAB-185). Twelve hours later, ferrets were challenged by mucosal inoculation with SARS-CoV-2. We found no significant differences in fever, weight loss, or viral shedding after infection between the three antibody groups or the controls. Signs of pathology in the lungs were noted in infected ferrets but no differences were found between control and antibody groups. The results of this study indicate that healthy, young adult ferrets of both sexes are a suitable model of mild COVID-19 and that low doses of specific IgG in SAB-185 are unlikely to enhance the disease caused by SARS-CoV-2.

BackgroundPoor mental health is associated with obesity, but existing studies are either cross-sectional or have long time periods between measurements of mental health and weight. It is, therefore, unclear how small fluctuations in mental wellbeing within individuals predict bodyweight over short time periods, e.g. within the next month. Studying this could identify modifiable determinants of weight changes and highlight opportunities for early intervention.Methods2,133 UK adults from a population-based cohort completed monthly mental health and weight measurements using a mobile app over a period of 6-9 months. We used random intercept regression models to examine longitudinal associations of depressive symptoms, anxiety symptoms and stress with subsequent weight. In sub-group analyses, we included interaction terms of mental health variables with baseline characteristics. Mental health variables were split into "between-individual" measurements (= the participant's median score across all timepoints) and "within-individual" measurements (at each timepoint, the difference between the participant's current score and their median).ResultsWithin-individual variation in depressive symptoms predicted subsequent weight (0.045kg per unit of depressive symptom severity, 95% CI 0.021-0.069). We found evidence of a moderation effect of baseline BMI on the association between within-individual fluctuation in depressive symptoms and subsequent weight: The association was only apparent in those with overweight/obesity, and it was stronger in those with obesity than those with overweight (BMIConclusionIn this exploratory study, individuals with overweight or obesity were more vulnerable to weight gain following higher-than-usual (for that individual) depressive symptoms than individuals with a BMI

The Eating Disorders In weight-related Therapy (EDIT) Collaboration brings together data from randomised controlled trials of behavioural weight management interventions to identify individual participant risk factors and intervention strategies that contribute to eating disorder risk. We present a protocol for a systematic review and individual participant data (IPD) meta-analysis which aims to identify participants at risk of developing eating disorders, or related symptoms, during or after weight management interventions conducted in adolescents or adults with overweight or obesity. We systematically searched four databases up to March 2022 and clinical trials registries to May 2022 to identify randomised controlled trials of weight management interventions conducted in adolescents or adults with overweight or obesity that measured eating disorder risk at pre- and post-intervention or follow-up. Authors from eligible trials have been invited to share their deidentified IPD. Two IPD meta-analyses will be conducted. The first IPD meta-analysis aims to examine participant level factors associated with a change in eating disorder scores during and following a weight management intervention. To do this we will examine baseline variables that predict change in eating disorder risk within intervention arms. The second IPD meta-analysis aims to assess whether there are participant level factors that predict whether participation in an intervention is more or less likely than no intervention to lead to a change in eating disorder risk. To do this, we will examine if there are differences in predictors of eating disorder risk between intervention and no-treatment control arms. The primary outcome will be a standardised mean difference in global eating disorder score from baseline to immediately post-intervention and at 6- and 12- months follow-up. Identifying participant level risk factors predicting eating disorder risk will inform screening and monitoring protocols to allow early identification and intervention for those at risk.

BackgroundAntimicrobial Resistance (AMR) is a global problem with large health and economic consequences. Current gaps in quantitative data are a major limitation for creating models intended to simulate the drivers of AMR. As an intermediate step, expert knowledge and opinion could be utilized to fill gaps in knowledge for areas of the system where quantitative data does not yet exist or are hard to quantify. Therefore, the objective of this study was to identify quantifiable data about the current state of the factors that drive AMR and the strengths and directions of relationships between the factors from statements made by a group of experts from the One Health system that drives AMR development and transmission in a European context.MethodsThis study builds upon previous work that developed a causal loop diagram of AMR using input from two workshops conducted in 2019 in Sweden with experts within the European food system context. A secondary analysis of the workshop transcripts was conducted to identify semi-quantitative data to parameterize drivers in a model of AMR.Main findingsParticipants spoke about AMR by combining their personal experiences with professional expertise within their fields. The analysis of participants' statements provided semi-quantitative data that can help inform a future of AMR emergence and transmission based on a causal loop diagram of AMR in a Swedish One Health system context.ConclusionUsing transcripts of a workshop including participants with diverse expertise across the system that drives AMR, we gained invaluable insight into the past, current, and potential future states of the major drivers of AMR, particularly where quantitative data are lacking.

Body mass dynamics of animals can indicate critical associations between extrinsic factors and population vital rates. Photogrammetry can be used to estimate mass of individuals in species whose life histories make it logistically difficult to obtain direct body mass measurements. Such studies typically use equations to relate volume estimates from photogrammetry to mass; however, most fail to identify the sources of error between the estimated and actual mass. Our objective was to identify the sources of error that prevent photogrammetric mass estimation from directly predicting actual mass, and develop a methodology to correct this issue. To do this, we obtained mass, body measurements, and scaled photos for 56 sedated Weddell seals (Leptonychotes weddellii). After creating a three-dimensional silhouette in the image processing program PhotoModeler Pro, we used horizontal scale bars to define the ground plane, then removed the below-ground portion of the animal's estimated silhouette. We then re-calculated body volume and applied an expected density to estimate animal mass. We compared the body mass estimates derived from this silhouette slice method with estimates derived from two other published methodologies: body mass calculated using photogrammetry coupled with a species-specific correction factor, and estimates using elliptical cones and measured tissue densities. The estimated mass values (mean ± standard deviation 345±71 kg for correction equation, 346±75 kg for silhouette slice, 343±76 kg for cones) were not statistically distinguishable from each other or from actual mass (346±73 kg) (ANOVA with Tukey HSD post-hoc, p>0.05 for all pairwise comparisons). We conclude that volume overestimates from photogrammetry are likely due to the inability of photo modeling software to properly render the ventral surface of the animal where it contacts the ground. Due to logistical differences between the "correction equation", "silhouette slicing", and "cones" approaches, researchers may find one technique more useful for certain study programs. In combination or exclusively, these three-dimensional mass estimation techniques have great utility in field studies with repeated measures sampling designs or where logistic constraints preclude weighing animals.

Recent avian and swine-origin influenza virus outbreaks illustrate the ongoing threat of influenza pandemics. We investigated immunogenicity and protective efficacy of a multi-antigen (MA) universal influenza DNA vaccine consisting of HA, M2, and NP antigens in cynomolgus macaques. Following challenge with a heterologous pandemic H1N1 strain, vaccinated animals exhibited significantly lower viral loads and more rapid viral clearance when compared to unvaccinated controls. The MA DNA vaccine induced robust serum and mucosal antibody responses but these high antibody titers were not broadly neutralizing. In contrast, the vaccine induced broadly-reactive NP specific T cell responses that cross-reacted with the challenge virus and inversely correlated with lower viral loads and inflammation. These results demonstrate that a MA DNA vaccine that induces strong cross-reactive T cell responses can, independent of neutralizing antibody, mediate significant cross-protection in a nonhuman primate model and further supports development as an effective approach to induce broad protection against circulating and emerging influenza strains.

Since SARS-CoV-2 emerged in late 2019, it spread from China to the rest of the world. An initial concern was the potential for vaccine- or antibody-dependent enhancement (ADE) of disease as had been reported with other coronaviruses. To evaluate this, we first developed a ferret model by exposing ferrets to SARS-CoV-2 by either mucosal inoculation (intranasal/oral/ocular) or inhalation using a small particle aerosol. Mucosal inoculation caused a mild fever and weight loss that resolved quickly; inoculation via either route resulted in virus shedding detected in the nares, throat, and rectum for 7–10 days post-infection. To evaluate the potential for ADE, we then inoculated groups of ferrets intravenously with 0.1, 0.5, or 1 mg/kg doses of a human polyclonal anti-SARS-CoV-2 IgG from hyper-immunized transchromosomic bovines (SAB-185). Twelve hours later, ferrets were challenged by mucosal inoculation with SARS-CoV-2. We found no significant differences in fever, weight loss, or viral shedding after infection between the three antibody groups or the controls. Signs of pathology in the lungs were noted in infected ferrets but no differences were found between control and antibody groups. The results of this study indicate that healthy, young adult ferrets of both sexes are a suitable model of mild COVID-19 and that low doses of specific IgG in SAB-185 are unlikely to enhance the disease caused by SARS-CoV-2. [ABSTRACT FROM AUTHOR]

In endometrial cancer, occult high-risk subtypes (rooted in histomorphologically low-risk disease) with insensitivity to adjuvant therapies impede improvements in therapeutic efficacy. Therefore, we aimed to assess the ability of molecular high-risk (MHR) and low-risk (MLR) ECPPF (E2F1, CCNA2, POLE, PPP2R1A, FBXW7) stratification to profile recurrence in early, low-risk endometrioid endometrial cancer (EEC) and insensitivity to platinum-based chemotherapy or radiotherapy (or both) in high-risk EEC. Using The Cancer Genome Atlas endometrial cancer database, we identified 192 EEC cases with available DNA sequencing and RNA expression data. Molecular parameters were integrated with clinicopathologic risk factors and adverse surveillance events. MHR was defined as high (-H) CCNA2 or E2F1 log2 expression (≥2.75), PPP2R1A mutations (-mu), or FBXW7mu; MLR was defined as low (-L) CCNA2 and E2F1 log2 expression (

Habitat modification and introduced mammalian predators are linked to global species extinctions and declines, but their relative influences can be uncertain, often making conservation management difficult. Using landscape-scale models, we quantified the relative impacts of habitat modification and mammalian predation on the range contraction of a threatened New Zealand riverine duck. We combined 38 years of whio (Hymenolaimus malacorhynchos) observations with national-scale environmental data to predict relative likelihood of occurrence (RLO) under two scenarios using bootstrapped boosted regression trees (BRT). Our models used training data from contemporary environments to predict the potential contemporary whio distribution across New Zealand riverscapes in the absence of introduced mammalian predators. Then, using estimates of environments prior to human arrival, we used the same models to hindcast potential pre-human whio distribution prior to widespread land clearance. Comparing RLO differences between potential pre-human, potential contemporary and observed contemporary distributions allowed us to assess the relative impacts of the two main drivers of decline; habitat modification and mammalian predation. Whio have undergone widespread catastrophic declines most likely linked to mammalian predation, with smaller declines due to habitat modification (range contractions of 95% and 37%, respectively). We also identified areas of potential contemporary habitat outside their current range that would be suitable for whio conservation if mammalian predator control could be implemented. Our approach presents a practical technique for estimating the relative importance of global change drivers in species declines and extinctions, as well as providing valuable information to improve conservation planning.

BackgroundAmong older adults, decreased handgrip strength is associated with greater risk of frailty, and loss of physical function, mobility, lean mass, and overall muscular strength and power. Frailty is also associated with sarcopenia, for which handgrip strength measurement has been recommended for diagnostic purposes. Specific cutoff points for diagnosis have been identified, but use of different devices may affect measurement. Therefore to assess validity and reliability, we compared the two most frequently used devices, the Jamar hydraulic and Smedley spring handgrip dynamometers.MethodsSixty-seven older (76.2 ± 0.9 years) men (n = 34) and women (n = 33) completed two trials of handgrip strength measurement on sequential days (T1, T2) using both devices in random order. Intraclass correlations were used to assess test-retest reliability, and Bland-Altman analysis was used to assess validity as the level of agreement between devices.ResultsThere were significant (p < 0.001) relationships between devices at T1 (r = 0.94) and T2 (r = 0.94) and strong (p < 0.001) intraclass correlations were observed for both devices (Jamar = 0.98; Smedley = 0.96), indicating excellent reliability. However, there were significant differences between devices. Strength measured with Jamar was greater than Smedley at both T1 (27.4 ± 1.4 vs. 23.4 ± 1.1 kg, p < 0.001) and T2 (25.3 ± 1.4 vs. 21.8 ± 1.2 kg, p < 0.001). Bland-Altman analysis confirmed these differences. Subgroup analysis to evaluate the effect of gender and age indicated that in women and old-old (>75 years) participants, differences between devices were closer to zero for both measurements compared to men and young-old (65-75 years) participants.ConclusionsOur results demonstrate that despite excellent reliability, there is poor agreement between devices, indicating a lack of validity. For use as a diagnostic tool, standardization and device-specific cutoff points for handgrip dynamometry are needed.

BackgroundTo investigate changes in sociocultural stressors and protective factors, and mental health in Latina mothers before and after the 2016 Republican presidential nomination.MethodsWe examined changes in sociocultural stressors, protective factors, and mental health from two prospective cohorts of Latina mothers from interior and border US cities (Nashville, TN, n = 39 and San Diego, CA, ns range = 78-83; 2013-2020).ResultsWe identified significant longitudinal increases in depression, anxiety, and perceived stress in the border city, and reductions in protective factors (e.g., optimism, social support, and familism) across sites. Discrimination varied by location, and was associated with higher stress only at baseline in the border city, and with higher anxiety in the interior city at follow-up. Acculturative stress was consistently associated with worse mental health across time points in the border city. Various protective factors were associated with reduced stress and anxiety across time points in both cities.DiscussionWe identified decreased mental health at the border city, and reduced protective factors in Latina mothers across both study sites in the years following the 2016 presidential nomination, during a time of shifting sociopolitical climate. We also identify increased acculturative stress and discrimination over time, particularly at the border city. Interventions to maintain and enhance psychosocial protective factors amongst Latina mothers are warranted.

Background Cerebral palsy (CP) is a complex neuromuscular condition that may negatively influence gross motor function. Children diagnosed with CP often exhibit spasticity, weakness, reduced motor control, contracture, and bony malalignment. Despite many previous association studies, the causal impact of these impairments on motor function is unknown. Aim In this study, we proposed a causal model which estimated the effects of common impairments on motor function in children with spastic CP as measured by the 66-item Gross Motor Function Measure (GMFM-66). We estimated both direct and total effect sizes of all included variables using linear regression based on covariate adjustment sets implied by the minimally sufficient adjustment sets. In addition, we estimated bivariate effect sizes of all measures for comparison. Method We retrospectively evaluated 300 consecutive subjects with spastic cerebral palsy who underwent routine clinical gait analysis. Model data included standard information collected during this analysis. Results The largest causal effect sizes, as measured by standardized regression coefficients, were found for selective voluntary motor control and dynamic motor control, followed by strength, then gait deviations. In contrast, common treatment targets, such as spasticity and orthopedic deformity, had relatively small effects. Effect sizes estimated from bivariate models, which cannot appropriately adjust for other causal factors, substantially overestimated the total effect of spasticity, strength, and orthopedic deformity. Interpretation Understanding the effects of impairments on gross motor function will allow clinicians to direct treatments at those impairments with the greatest potential to influence gross motor function and provide realistic expectations of the anticipated changes.

Age and gender differences are prominent in the temperament literature, with the former particularly salient in infancy and the latter noted as early as the first year of life. This study represents a meta-analysis utilizing Infant Behavior Questionnaire-Revised (IBQ-R) data collected across multiple laboratories (N = 4438) to overcome limitations of smaller samples in elucidating links among temperament, age, and gender in early childhood. Algorithmic modeling techniques were leveraged to discern the extent to which the 14 IBQ-R subscale scores accurately classified participating children as boys (n = 2,298) and girls (n = 2,093), and into three age groups: youngest (< 24 weeks; n = 1,102), mid-range (24 to 48 weeks; n = 2,557), and oldest (> 48 weeks; n = 779). Additionally, simultaneous classification into age and gender categories was performed, providing an opportunity to consider the extent to which gender differences in temperament are informed by infant age. Results indicated that overall age group classification was more accurate than child gender models, suggesting that age-related changes are more salient than gender differences in early childhood with respect to temperament attributes. However, gender-based classification was superior in the oldest age group, suggesting temperament differences between boys and girls are accentuated with development. Fear emerged as the subscale contributing to accurate classifications most notably overall. This study leads infancy research and meta-analytic investigations more broadly in a new direction as a methodological demonstration, and also provides most optimal comparative data for the IBQ-R based on the largest and most representative dataset to date.

BackgroundPublic health officials have classified smoking as a risk factor for COVID-19 disease severity. Smokers generally have less trust in health experts than do nonsmokers, leading to reduced risk perceptions. This study addresses smokers' trust in information sources about COVID-19 and how trust is associated with perceived COVID-19 susceptibility and severity among smokers.Methods and findingsA nationally representative sample of 1,223 current smokers were surveyed between October and November 2020, indicating their level of trust in COVID-19 information sources, and their perceptions of risk from COVID-19. Multiple differences in trustworthiness emerged; smokers trusted their personal doctor for information about COVID-19 more than other information sources, while news media were generally distrusted. In addition, the FDA was trusted less than the NIH and CDC. Several "trust gaps" were observed, indicating disparities in levels of trust associated with gender, ethnicity, education, and political orientation, which had the strongest association with trust of all factors. Political orientation was also a significant predictor of COVID-19 risk perceptions, but there was no independent effect of political orientation when accounting for trust, which was predictive of all risk perception outcomes.ConclusionsTrusted sources, such as personal doctors, may most effectively convey COVID-19 information across political orientations and sociodemographic groups. News media may be ineffective at informing smokers due to their low credibility. The results suggest that trust may explain the apparent effect of political orientation on COVID-19 risk perceptions. Implications for researchers, communication professionals, and policy makers are discussed.

Endometriosis affects reproductive-aged females and varies considerably in terms of symptom presentation, morphologic features, and treatment response. Most studies investigating symptom recurrence after an endometriosis-related surgery have been conducted among adults. The Endometriosis pain QUality aftEr Surgical Treatment (EndoQUEST) Study was established to assess characteristics and biomarkers that are associated with pain remediation and improved quality of life after an endometriosis-related surgery among adolescents and young adults. This paper describes the EndoQUEST methodology, summarizes baseline descriptive factors, and compares characteristics by participant retention status. We enrolled 100 surgically-confirmed endometriosis participants aged 12-23 years who provided questionnaire data on reproductive and behavioral factors, pain characteristics and quality of life at three time points; before surgery, 6 weeks to 26 weeks after surgery, and 1 year after surgery. Among these 100 participants, 88 provided blood and/or saliva at all three time points, while 12 provided blood and/or saliva samples only before surgery and 6 to 26 weeks after surgery. There was little evidence of lost to follow-up at 1 year after surgery due to pain symptoms, as pain and quality of life characteristics were similar between participants who completed the questionnaire 1 year after surgery and those who did not. Analyses utilizing these longitudinal data will advance personalized treatment decision making for adolescents and young adults with endometriosis.

A surface plasmon polariton (SPP) is an excitation resulting from the coupling of light to a surface charge oscillation at a metal-dielectric interface. The excitation and detection of SPPs is foundational to the operating mechanism of a number of important technologies, most of which require SPP excitation via direct reflectance, commonly achieved via Attenuated Total Reflection (ATR) using the Kretschmann configuration. As a result, the accessible modes are fundamentally high-loss "leaky modes," presenting a critical performance barrier. Recently, our group provided the first demonstration of "forbidden," or guided-wave plasmon polariton modes (GW-PPMs), collective modes of a MIM structure with oscillatory electric field amplitude in the central insulator layer with up to an order of magnitude larger propagation lengths than those of traditional SPPs. However, in that work, GW-PPMs were accessed by indirect reflectance using Otto configuration ATR, making them of limited applied relevance. In this paper, we demonstrate a technique for direct reflectance excitation and detection of GW-PPMs. Specifically, we replace the air gap used in traditional Otto ATR with a low refractive index polymer coupling layer, mirroring a technique previously demonstrated to access Long-Range Surface Plasmon Polariton modes. We fit experimental ATR data using a robust theoretical model to confirm the character of the modes, as well as to explore the potential of this approach to enable advantageous propagation lengths. The ability to excite GW-PPMs using a device configuration that does not require an air gap could potentially enable transformative performance enhancements in a number of critical technologies.

IntroductionAbiraterone acetate and enzalutamide are commonly employed in prostate cancer therapy in an interchangeable manner. These drugs are highly efficacious in androgen antagonism to improve patient outcomes, but they also carry noteworthy risk of adverse effects. Common toxicities vary amongst the two drugs and may have differential interactions with patient co-morbidities, but these patterns are unclear as co-morbidities typically serve as exclusion criteria in clinical trials. Hence, there is no existing guidance on how clinicians may tailor treatment based on patient-specific factors. Analysis of differential patient outcomes between these two drugs can inform future systematic reviews, new clinical studies, and clinical decision making.Method and analysisThe framework for this methodology was informed by the Joanna Briggs Institute methodology for scoping reviews. Title and abstract screening will be performed by two independent researchers to create an initial study inventory. This will be followed by full-text screening for study inclusion. Population-based studies describing patient outcomes, common toxicities, and associations with patient co-morbidities following abiraterone or enzalutamide therapy will be included. After data is extracted, it will be summarized for presentation.Ethics and disseminationThe findings of this scoping review will be published in a peer-reviewed journal. The results will be used to inform future studies on patient-specific factors informing treatment choice between abiraterone and enzalutamide for castration-resistant prostate cancer. All data are from published openly accessible sources, and therefore, no ethical clearance is necessary. The protocol is also registered at https://doi.org/10.6084/m9.figshare.19149227.

Domestication is the hallmark of evolution and civilization and harnesses biodiversity through selection for specific traits. In regions where domesticated lines are grown near wild relatives, congeneric sources of aggressive weedy genotypes cause major economic losses. Thus, the origins of weedy genotypes where no congeneric species occur raise questions regarding management effectiveness and evolutionary mechanisms responsible for weedy population success. Since eradication in the 1970s, California growers avoided weedy rice through continuous flood culture and zero-tolerance guidelines, preventing the import, presence, and movement of weedy seeds. In 2003, after decades of no reported presence in California, a weedy rice population was confirmed in dry-seeded fields. Our objectives were to identify the origins and establishment of this population and pinpoint possible phenotypes involved. We show that California weedy rice is derived from a different genetic source among a broad range of AA genome Oryzas and is most recently diverged from O. sativa temperate japonica cultivated in California. In contrast, other weedy rice ecotypes in North America (Southern US) originate from weedy genotypes from China near wild Oryza, and are derived through existing crop-wild relative crosses. Analyses of morphological data show that California weedy rice subgroups have phenotypes like medium-grain or gourmet cultivars, but have colored pericarp, seed shattering, and awns like wild relatives, suggesting that reversion to non-domestic or wild-like traits can occur following domestication, despite apparent fixation of domestication alleles. Additionally, these results indicate that preventive methods focused on incoming weed sources through contamination may miss burgeoning weedy genotypes that rapidly adapt, establish, and proliferate. Investigating the common and unique evolutionary mechanisms underlying global weed origins and subsequent interactions with crop relatives sheds light on how weeds evolve and addresses broader questions regarding the stability of selection during domestication and crop improvement.

This study examined whether stress at work and at home may be related to dysregulation of inflammation and endothelial function, two important contributors to the development of cardiovascular disease. In order to explore potential biological mechanisms linking stress with cardiovascular health, we investigated cross-sectional associations between stress at work and at home with an inflammation score (n's range from 406-433) and with two endothelial biomarkers (intercellular and vascular adhesion molecules, sICAM-1 and sVCAM-1; n's range from 205-235) in a cohort of healthy US male health professionals. No associations were found between stress at work or at home and inflammation. Men with high or medium levels of stress at work had significantly higher levels of sVCAM-1 (13% increase) and marginally higher levels of sICAM-1 (9% increase), relative to those reporting low stress at work, independent of health behaviors. Men with high levels of stress at home had marginally higher levels of both sVCAM-1 and sICAM-1 than those with low stress at home. While lack of findings related to inflammation are somewhat surprising, if replicated in future studies, these findings may suggest that endothelial dysfunction is an important biological mechanism linking stress at work with cardiovascular health outcomes in men.

The experimental objective was to characterize the impact of insoluble corn-based fiber, xylanase, and an arabinoxylan-oligosaccharide on ileal digesta and mucosa microbiome of pigs. Three replicates of 20 gilts were blocked by initial body weight, individually-housed, and assigned to 1 of 4 dietary treatments: a low-fiber control (LF), a 30% corn bran high-fiber control (HF), HF+100 mg/kg xylanase (HF+XY), and HF+50 mg/kg arabinoxylan oligosaccharide (HF+AX). Gilts were fed their respective treatments for 46 days. On day 46, pigs were euthanized and ileal digesta and mucosa were collected. The V4 region of the 16S rRNA was amplified and sequenced, generating a total of 2,413,572 and 1,739,013 high-quality sequences from the digesta and mucosa, respectively. Sequences were classified into 1,538 mucosa and 2,495 digesta operational taxonomic units (OTU). Hidden-state predictions of 25 enzymes were made using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 2 (PICRUST2). Compared to LF, HF increased Erysipelotrichaceae_UCG-002, and Turicibacter in the digesta, Lachnospiraceae_unclassified in the mucosa, and decreased Actinobacillus in both (Q

Tumor angiogenesis is critical for the growth and progression of cancer. As such, angiostasis is a treatment modality for cancer with potential utility for multiple types of cancer and fewer side effects. However, clinical success of angiostatic monotherapies has been moderate, at best, causing angiostatic treatments to lose their early luster. Previous studies demonstrated compensatory mechanisms that drive tumor vascularization despite the use of angiostatic monotherapies, as well as the potential for combination angiostatic therapies to overcome these compensatory mechanisms. We screened clinically approved angiostatics to identify specific combinations that confer potent inhibition of tumor-induced angiogenesis. We used a novel modification of the ex ovo chick chorioallantoic membrane (CAM) model that combined confocal and automated analyses to quantify tumor angiogenesis induced by glioblastoma tumor onplants. This model is advantageous due to its low cost and moderate throughput capabilities, while maintaining complex in vivo cellular interactions that are difficult to replicate in vitro. After screening multiple combinations, we determined that glioblastoma-induced angiogenesis was significantly reduced using a combination of bevacizumab (Avastin®) and temsirolimus (Torisel®) at doses below those where neither monotherapy demonstrated activity. These preliminary results were verified extensively, with this combination therapy effective even at concentrations further reduced 10-fold with a CI value of 2.42E-5, demonstrating high levels of synergy. Thus, combining bevacizumab and temsirolimus has great potential to increase the efficacy of angiostatic therapy and lower required dosing for improved clinical success and reduced side effects in glioblastoma patients.

ObjectiveTo compare the effectiveness and safety of prescribing ibuprofen and oxycodone for at-home management of children's fracture pain.MethodsA prospective observational cohort was conducted at the Stollery Children's Hospital pediatric emergency department (June 2010-July 2014). Children aged 4-16 years with an isolated fracture discharged home with advice to use either ibuprofen or oxycodone were recruited.ResultsA cohort of 329 children (n = 217 ibuprofen, n = 112 oxycodone) were included. Mean age was 11.1 years (SD 3.5); 68% (223/329) were male. Fracture distribution included 80.5% (264/329) upper limb with 34.3% (113/329) requiring fracture reduction. The mean reduction in Faces Pain Score-Revised score (maximum pain-post-treatment pain) for Day 1 was 3.6 (SD 1.9) (ibuprofen) and 3.8 (SD 2.1) (oxycodone) (p = 0.50); Day 2 was 3.6 (SD 1.8) (ibuprofen) and 3.7 (SD 1.6) (oxycodone) (p = 0.56); Day 3 was 3.7 (SD 1.7) (ibuprofen) and 3.3 (SD 1.7) (oxycodone) (p = 0.24). Children prescribed ibuprofen (51.2%, 109/213) experienced less adverse events compared to those prescribed oxycodone (70.5% 79/112) on Day 1 (p = 0.001). Children prescribed ibuprofen (71.8%, 150/209) had their function (eat, play, school, sleep) affected less than those prescribed oxycodone (83.0%, 93/112) (p = 0.03) on Day 1.ConclusionChildren prescribed ibuprofen or oxycodone experienced similar analgesic effectiveness for at-home fracture pain. Oxycodone prescribing was associated with more adverse events and negatively impacted function. Oxycodone use does not appear to confer any benefit over ibuprofen for pain relief and has a negative adverse effect profile. Ibuprofen appears to be a safe option for fracture-related pain.

Wildlife-vehicle collisions are one of the main causes of mortality for wild mammals and birds in the UK. Here, using a dataset of 54,000+ records collated by a citizen science roadkill recording scheme between 2014-2019, we analyse and present temporal patterns of wildlife roadkill of the 19 most commonly reported taxa in the UK (84% of all reported roadkill). Most taxa (13 out of 19) showed significant and consistent seasonal variations in road mortality and fitted one of two seasonal patterns; bimodal or unimodal: only three species (red fox Vulpes vulpes, European polecat Mustela putorius and Reeves' muntjac deer Muntiacus reevesi) showed no significant seasonality. Species that increase movement in spring and autumn potentially have bimodal patterns in roadkill due to the increase in mate-searching and juvenile dispersal during these respective time periods (e.g. European badger Meles meles). Unimodal patterns likely represent increased mortality due to a single short pulse in activity associated with breeding (e.g. birds) or foraging (e.g. grey squirrels Sciurus carolinensis in autumn). Importantly, these patterns also indicate periods of increased risk for drivers, potentially posing a greater threat to human welfare. In addition to behaviour-driven annual patterns, abiotic factors (temperature and rainfall) explained some variance in roadkill. Notably, high rainfall was associated with decreased observations of two bird taxa (gulls and Eurasian magpies Pica pica) and European rabbit Oryctolagus cuniculus. By quantifying seasonal patterns in roadkill, we highlight a significant anthropogenic impact on wild species, which is important in relation to conservation, animal welfare, and human safety.

Multi-drug resistant (MDR) Acinetobacter baumannii (Ab) and Acinetobacter spp. present monumental global health challenges. These organisms represent model Gram-negative pathogens with known antibiotic resistance and biofilm-forming properties. Herein, a novel, nontoxic biocide, AB569, consisting of acidified nitrite (A-NO2-) and ethylenediaminetetraacetic acid (EDTA), demonstrated bactericidal activity against all Ab and Acinetobacter spp. strains, respectively. Average fractional inhibitory concentrations (FICs) of 0.25 mM EDTA plus 4 mM A-NO2- were observed across several clinical reference and multiple combat wound isolates from the Iraq/Afghanistan wars. Importantly, toxicity testing on human dermal fibroblasts (HDFa) revealed an upper toxicity limit of 3 mM EDTA plus 64 mM A-NO2-, and thus are in the therapeutic range for effective Ab and Acinetobacter spp. treatment. Following treatment of Ab strain ATCC 19606 with AB569, quantitative PCR analysis of selected genes products to be responsive to AB569 revealed up-regulation of iron regulated genes involved in siderophore production, siderophore biosynthesis non-ribosomal peptide synthetase module (SBNRPSM), and siderophore biosynthesis protein monooxygenase (SBPM) when compared to untreated organisms. Taken together, treating Ab infections with AB569 at inhibitory concentrations reveals the potential clinical application of preventing Ab from gaining an early growth advantage during infection followed by extensive bactericidal activity upon subsequent exposures.

BackgroundParent mental health and wellbeing may have implications for understanding attachment transmission. In this systematic review, we synthesise the published literature to determine the nature of the relationship between parent mental health and wellbeing and the intergenerational transmission of attachment and to provide recommendations for future research, clinical practice and intervention.MethodUsing the preferred reporting items for systematic reviews and meta-analyses (PRISMA) approach, five electronic databases were searched for peer-reviewed empirical studies, published in English. Articles were considered for inclusion if data was collected on adult attachment, child attachment, and a domain of parent mental health/wellbeing. No date parameters were applied to the search strategy. The review was registered with PROPSERO (registration number: CRD42020157247).ResultsEleven studies examining the impact on parent mental health and wellbeing on the intergenerational transmission of attachment were identified for inclusion in this review. Our review found preliminary evidence that parent mental health and wellbeing play a role in the intergenerational transmission of attachment. Other key findings from the review were: evidence quality is mixed due to variable measurement of attachment and mental health; studies have mostly included correlational analysis or do not utilise contemporary methodological approaches to testing mediating or moderating relationships; and literature is largely focused on psychopathology and negative factors of mental health.ConclusionsThe limited scope of parent mental health and wellbeing constructs examined in the literature, the sparse use of robust statistical analyses, and the lack of literature in general makes it difficult to draw conclusions on how and why parent mental health impacts attachment transmission. Addressing these limitations will further progress attachment-related literature and may have particular implications for attachment-informed interventions with clinical populations.

ObjectiveProspective studies on relationships between hedonic hunger and BMI (Body Mass Index) during weight management are lacking. This study examined if hedonic hunger reduced during a behavioural weight management programme, and if hedonic hunger predicted future BMI.MethodsParticipants were 594 community-dwelling, UK-based adults(396 female; age 56.43 years, s.d. = 12.50, range 20-83 years); 490 participants (82.5%) had obesity. Participants were randomised to a 12- or 52-week behavioural weight management intervention (WW12 or WW52, respectively) or a brief self-help intervention (BI). Relationships between hedonic hunger and BMI over 24 months (baseline, 3, 12, 24 months) were analysed using an autoregressive cross-lagged model.ResultsHedonic hunger scores decreased from 2.71 (s.d. = .91) at baseline to 2.41 (s.d. = .88) at 3 months (p < .001, CI .22 to .38), remained reduced to 24 months, and were not affected by intervention arm at any time point (p's>.05). Baseline hedonic hunger scores predicted 3-month scores (B = .76, SE = .03, p < .001, CI .71 to .82), 3-month scores predicted 12-month scores (B = .76, SE = .03, p < .001 CI .72 to .80), and 12-month scores predicted 24-month scores (B = .72, SE = .03, p < .001, CI .64 to .77). Higher hedonic hunger at 3 months predicted higher BMI at 12 months (B = .04, SE = .02, p = .03, CI .01 to .07) but not at 24 months (p>.05). BMI at 12 months was lower in WW52 30.87kg/m2, s.d. = 5.02) than WW12 (32.12 kg/m2, s.d. = 5.58, p = .02, CI .16 to 2.34) and BI (32.74 kg/m2, s.d. = 4.15, p = .01, CI .30 to 3.45). BMI was not affected by intervention at any other time point (p's>.05).ConclusionHedonic hunger reduced during weight management irrespective of intervention. Early reductions in hedonic hunger appear to be associated with lower BMI in the medium-term. Identifying ways to reduce hedonic hunger during weight loss could aid weight management for some people.

[This corrects the article DOI: 10.1371/journal.pone.0226113.].

The objectives of this research were to describe the contact structure of transportation vehicles and swine facilities in an Ontario swine production system, and to assess their potential contribution to possible disease transmission over different time periods. A years' worth of data (2015) was obtained from a large swine production and data management company located in Ontario, Canada. There was a total of 155 different transportation vehicles, and 220 different farms within the study population. Two-mode networks were constructed for 1-,3-, and 7-day time periods over the entire year and were analyzed. Trends in the size of the maximum weak component and outgoing contact chain over discrete time periods were investigated using linear regression. Additionally, the number of different types of facilities with betweenness >0 and in/out degree>0 were analyzed using Poisson regression. Maximum weekly outgoing contact chain (MOCCw) contained between 2.1% and 7.1% of the study population. This suggests a potential maximum of disease spread within this population if the disease was detected within one week. Frequency of node types within MOCCw showed considerable variability; although nursery sites were relatively most frequent. The regression analysis of several node and network level statistics indicated a potential peak time of connectivity during the summer months and warrants further confirmation and investigation. The inclusion of transportation vehicles contributed to the linear increase in the maximum weekly weak component (MWCw) size over time. This finding in combination with constant population dynamics, may have been driven by the differential utilization of trucks over time. Despite known limitations of maximum weak components as an estimator of possible outbreaks, this finding suggests that transportation vehicles should be included, when possible and relevant, in the evaluation of contacts between farms.

Alphaviruses such as Venezuelan equine encephalitis virus (VEEV) and Eastern equine encephalitis virus (EEEV) are arboviruses that can cause severe zoonotic disease in humans. Both VEEV and EEEV are highly infectious when aerosolized and can be used as biological weapons. Vaccines and therapeutics are urgently needed, but efficacy determination requires animal models. The cynomolgus macaque (Macaca fascicularis) provides a relevant model of human disease, but questions remain whether vaccines or therapeutics can mitigate CNS infection or disease in this model. The documentation of alphavirus encephalitis in animals relies on traditional physiological biomarkers and behavioral/neurological observations by veterinary staff; quantitative measurements such as electroencephalography (EEG) and intracranial pressure (ICP) can recapitulate underlying encephalitic processes. We detail a telemetry implantation method suitable for continuous monitoring of both EEG and ICP in awake macaques, as well as methods for collection and analysis of such data. We sought to evaluate whether changes in EEG/ICP suggestive of CNS penetration by virus would be seen after aerosol exposure of naïve macaques to VEEV IC INH9813 or EEEV V105 strains compared to mock-infection in a cohort of twelve adult cynomolgus macaques. Data collection ran continuously from at least four days preceding aerosol exposure and up to 50 days thereafter. EEG signals were processed into frequency spectrum bands (delta: [0.4 - 4Hz); theta: [4 - 8Hz); alpha: [8-12Hz); beta: [12-30] Hz) and assessed for viral encephalitis-associated changes against robust background circadian variation while ICP data was assessed for signal fidelity, circadian variability, and for meaningful differences during encephalitis. Results indicated differences in delta, alpha, and beta band magnitude in infected macaques, disrupted circadian rhythm, and proportional increases in ICP in response to alphavirus infection. This novel enhancement of the cynomolgus macaque model offers utility for timely determination of onset, severity, and resolution of encephalitic disease and for the evaluation of vaccine and therapeutic candidates.

Endometriosis is a painful gynecologic disease affecting one in ten reproductive aged women worldwide. Few studies have correlated this symptomatology with biomarker levels among women with and without endometriosis, and no studies correlating pain with biomarker levels have been performed in young patient populations. The purpose of this study was to examine whether CA125 correlates with different types and severity of pain among adolescents and young women with and without endometriosis and assess its performance as an endometriosis biomarker among those presenting with dysmenorrhea in this young population. Reproductive-aged women with laparoscopically-confirmed endometriosis (n = 282) and controls (n = 293) who participated in The Women's Health Study: From Adolescence to Adulthood (A2A), a cohort of adolescents and young women enrolled from 2012-2018, were included in this cross-sectional analysis. Plasma CA125 values were measured using WERF EPHect compliant blood samples collected at enrollment. Average CA125 were calculated by self-reported pain type (i.e. dysmenorrhea, non-cyclic/general pelvic pain, dyspareunia), severity, and frequency in endometriosis cases and controls. Median age at blood draw was 24 years in controls and 17 years in cases, with 68% and 89% non-Hispanic white, respectively. Most endometriosis cases (95%) were rASRM stage I/II. Average CA125 values were 12.5 U/mL in controls and 12.1 U/mL in cases adjusted for age. CA125 did not differ by pain type, its severity, or frequency in endometriosis cases or controls. Among participants who reported dysmenorrhea, CA125 did not discriminate endometriosis cases from controls using cutoff of 35 U/mL (AUC = 0.51, 95%CI = 0.50-0.53). Among adolescents and young adult women, CA125 did not correlate with pain type. CA125 did not efficiently discriminate endometriosis cases from controls even when accounting for pain symptomatology. Average CA125 values were low in adolescents and young women in both endometriosis cases and controls, suggesting cautious interpretation may be needed when measuring CA125 in this population.

BackgroundRC-101 is a congener of the antiretroviral peptide retrocyclin, which we and others have reported is active against clinical HIV-1 isolates from all major clades, does not hemagglutinate, and is non-toxic and non-inflammatory in cervicovaginal cell culture. Herein, film-formulated RC-101 was assessed for its antiviral activity in vitro, safety in vivo, retention in the cervix and vagina, and ability to remain active against HIV-1 and SHIV after intravaginal application in macaques.Methodology/principal findingsRC-101 was formulated as a quick-dissolving film (2000 µg/film), retained complete activity in vitro as compared to unformulated peptide, and was applied intravaginally in six pigtailed macaques daily for four days. At one and four days following the final application, the presence of RC-101 was assessed in peripheral blood, cervicovaginal lavage, cytobrushed cervicovaginal cells, and biopsied cervical and vaginal tissues by quantitative western blots. One day following the last film application, cervical biopsies from RC-101-exposed and placebo-controlled macaques were collected and were subjected to challenge with RT-SHIV in an ex vivo organ culture model. RC-101 peptide was detected primarily in the cytobrush and biopsied cervical and vaginal tissues, with little to no peptide detected in lavage samples, suggesting that the peptide was associated with the cervicovaginal epithelia. RC-101 remained in the tissues and cytobrush samples up to four days post-application, yet was not detected in any sera or plasma samples. RC-101, extracted from cytobrushes obtained one day post-application, remained active against HIV-1 BaL. Importantly, cervical biopsies from RC-101-treated animals reduced RT-SHIV replication in ex vivo organ culture as compared to placebo-treated animals.Conclusions/significanceFormulated RC-101 was stable in vivo and was retained in the mucosa. The presence of antivirally active RC-101 after five days in vivo suggests that RC-101 would be an important molecule to develop further as a topical microbicide to prevent HIV-1 transmission.

BackgroundTherapies directed at augmenting regulatory T cell (Treg) activities in vivo as a systemic treatment for autoimmune disorders and transplantation may be associated with significant off-target effects, including a generalized immunosuppression that may compromise beneficial immune responses to infections and cancer cells. Adoptive cellular therapies using purified expanded Tregs represents an attractive alternative to systemic treatments, with results from animal studies noting increased therapeutic potency of antigen-specific Tregs over polyclonal populations. However, current methodologies are limited in terms of the capacity to isolate and expand a sufficient quantity of endogenous antigen-specific Tregs for therapeutic intervention. Moreover, FOXP3+ Tregs fall largely within the CD4+ T cell subset and are thus routinely MHC class II-specific, whereas class I-specific Tregs may function optimally in vivo by facilitating direct tissue recognition.Methodology/principal findingsTo overcome these limitations, we have developed a novel means for generating large numbers of antigen-specific Tregs involving lentiviral T cell receptor (TCR) gene transfer into in vitro expanded polyclonal natural Treg populations. Tregs redirected with a high-avidity class I-specific TCR were capable of recognizing the melanoma antigen tyrosinase in the context of HLA-A*0201 and could be further enriched during the expansion process by antigen-specific reactivation with peptide loaded artificial antigen presenting cells. These in vitro expanded Tregs continued to express FOXP3 and functional TCRs, and maintained the capacity to suppress conventional T cell responses directed against tyrosinase, as well as bystander T cell responses. Using this methodology in a model tumor system, murine Tregs designed to express the tyrosinase TCR effectively blocked antigen-specific effector T cell (Teff) activity as determined by tumor cell growth and luciferase reporter-based imaging.Conclusions/significanceThese results support the feasibility of class I-restricted TCR transfer as a promising strategy to redirect the functional properties of Tregs and provide for a more efficacious adoptive cell therapy.

Increased interest in renewable energy has fostered development of wind and solar energy facilities globally. However, energy development sometimes has negative environmental impacts, such as wildlife fatalities. Efforts by regional land managers to balance energy potential while minimizing fatality risk currently rely on datasets that are aggregated at continental, but not regional scales, that focus on single species, or that implement meta-analyses that inappropriately use inferential statistics. We compiled and summarized fatality data from 87 reports for solar and wind facilities in the Mojave and Sonoran Deserts region of southern California within the Desert Renewable Energy Conservation Plan area. Our goal was to evaluate potential temporal and guild-specific patterns in fatalities, especially for priority species of conservation concern. We also aimed to provide a perspective on approaches interpreting these types of data, given inherent limitations in how they were collected. Mourning doves (Zenaida macroura), Chukar (Alectoris chukar) and California Quail (Callipepla californica), and passerines (Passeriformes), accounted for the most commonly reported fatalities. However, our aggregated count data were derived from raw, uncorrected totals, and thus reflect an absolute minimum number of fatalities for the monitored period. Additionally, patterns in the raw data suggested that many species commonly documented as fatalities (e.g., waterbirds and other nocturnal migrants, bats) are rarely counted during typical pre-construction use surveys. This may explain the more commonly observed mismatch between pre-construction risk assessment and actual fatalities. Our work may serve to guide design of future scientific research to address temporal and spatial patterns in fatalities and to apply rigorous guild-specific survey methodologies to estimate populations at risk from renewable energy development. [ABSTRACT FROM AUTHOR]

Invasive predators have caused rapid declines in many native prey species across the globe. Predator invasion success may be attributed to prey naïveté, or the absence of anti-predator behavior between native and non-native species. An understanding of the effects of naïveté at different timescales since introduction and across multiple trophic levels is lacking, however, particularly in marine systems. Given the central role of trophic interactions in invasion dynamics, this knowledge gap limits the ability to predict high impact predator invasions. Naïveté was examined across three trophic levels of marine invertebrates: a native basal prey (hard clam), two non-native intermediate predators (the recently-introduced Asian shore crab and the long-established European green crab), a native intermediate predator (juvenile blue crabs), and a native top predator (adult blue crab). We hypothesized that naïveté would be more pronounced in trophic interactions involving the recently-introduced non-native predator in comparison to the long-established non-native and native intermediate predators. We further hypothesized that the recently-introduced intermediate predator would both benefit from naïveté of the native basal prey and be hindered by higher mortality through its own naïveté to the native top predator. To test these hypotheses, three laboratory experiments and a field experiment were used. Consistent with our hypotheses, basal prey naïveté was most pronounced with the recently-introduced intermediate predator, and this increased the predator's foraging success. This recently-introduced intermediate predator, however, exhibited an ineffective anti-predator response to the native top predator, and was also preyed upon more in the field than its long-established and native counterparts. Therefore, despite direct benefits from basal prey naïveté, the recently-introduced intermediate predator's naïveté to its own predators may limit its invasion success. These results highlight the importance of a multi-trophic perspective on predator-prey dynamics to more fully understand the consequences of naïveté in invasion biology.

Horses are a highly mobile population, with many travelling locally, nationally, and internationally to participate in shows and sporting events. However, the nature and extent of these movements, as well as the potential impact they may have on disease introduction and spread, is not well documented. The objective of this study was to characterise the movement network of a sample of horses in Ontario, Canada, over a 7-month equestrian season. Horse owners (n = 141) documented their travel patterns with their horse(s) (n = 330) by completing monthly online questionnaires between May and November 2015. Directed networks were constructed to represent horse movements in 1-month time periods. A total of 1754 horse movements met the inclusion criteria for analysis. A variety of location types were included in each monthly network, with many including non-facilities such as parks, trails, and private farms. Only 34.3% of competitions attended by participants during the study period were regulated by an official equestrian organisation. Comparisons of the similarity between monthly networks indicated that participants did not travel to the same locations each month, and the most connected locations varied between consecutive months. While the findings should not be generalized to the wider horse population, they have provided greater insight into the nature and extent of observed horse movement patterns. The results support the need to better understand the variety of locations to which horses can travel in Ontario, as different types of locations may have different associated risks of disease introduction and spread.

Carbapenemase-producing bacteria (CPB) are rare, multidrug resistant organisms most commonly associated with hospitalized patients. Metropolitan wastewater treatment plants (WWTP) treat wastewater from large geographic areas which include hospitals and may serve as epidemiologic reservoirs for the maintenance or expansion of CPB that originate from hospitals and are ultimately discharged in treated effluent. However, little is known about the potential impact of these WWTP CPB on the local surface water and their risk to the public health. In addition, CPB that are present in surface water may ultimately disseminate to intensively-managed animal agriculture facilities where there is potential for amplification by extended-spectrum cephalosporins. To better understand the role of WWTPs in the dissemination of CPB in surface waters, we obtained samples of treated effluent, and both upstream and downstream nearby surface water from 50 WWTPs throughout the US. A total of 30 CPB with clinically-relevant genotypes were recovered from 15 WWTPs (30%) of which 13 (50%) serviced large metropolitan areas and 2 (8.3%) represented small rural populations (P < 0.05). Recovery of CPB was lowest among WWTPs that utilized ultraviolet radiation for primary disinfection (12%), and higher (P = 0.11) for WWTPs that used chlorination (42%) or that did not utilize disinfection (50%). We did not detect a difference in CPB recovery by sampling site, although fewer CPB were detected in upstream (8%) compared to effluent (20%) and downstream (18%) samples. Our results indicate that WWTP effluent and nearby surface waters in the US are routinely contaminated with CPB with clinically important genotypes including those producing Klebsiella pneumoniae carbapenemase (KPC) and New Delhi metallo-beta-lactamase (NDM). This is a concern for both public health and animal agriculture because introduction of CPB into intensively managed livestock populations could lead to their amplification and foodborne dissemination.

Given the amount of time and effort individuals pour into work, scholars and practitioners alike have spent considerable time and resources trying to understand well-being in the workplace. Unfortunately, much of the current research and measurement focuses on workplace well-being from only one perspective (i.e. hedonic well-being rather than eudaimonic well-being) or by generalizing between workplace well-being and general well-being. In this study, we sought to integrate the workplace context into the current eudaimonic perspective to develop an 8-item measure of eudaimonic workplace well-being. Using multi-wave data, we developed and validated a reliable, two-dimensional eudaimonic workplace well-being scale (EWWS). The measure replicated over seven samples and across 1346 participants and showed strong convergent, discriminant, and predictive validity. Furthermore, we combined EWWS with an existing measure of hedonic workplace well-being and the resulting model of overall workplace well-being explained a significant amount of variance in key organizational constructs over and above existing hedonic well-being measures. Overall, the present study suggests that the EWWS is a valuable and valid measure and, when taken together with hedonic workplace well-being, captures what it means to have a holistic sense of well-being at work.

The bovine dry period is a non-lactating period between consecutive lactations characterized by mammary gland involution and redevelopment phases to replace senescent mammary epithelial cells with active cells primed for the next lactation. Dairy cows exposed to heat stress during the dry period experience milk yield reductions between 3-7.5 kg/d in the next lactation, partially attributed to processes associated with mammary cell growth and turnover during the dry period. However, the carry-over impact of dry period heat stress on mammary morphology during lactation has yet to be determined. In the current study, we hypothesized that exposure to heat stress during the dry period would alter alveolar microstructure and cellular turnover (i.e. proliferation and apoptosis) during lactation. Cows were either subjected to heat stress (HT, access to shade; n = 12) or cooling (CL, access to shade, fans, and soakers; n = 12) for a 46 d dry period. Upon calving, all cows were treated similarly with access to cooling for their entire lactation. Six cows per treatment were randomly selected for mammary gland biopsies at 14, 42, and 84 days in milk. Tissues were sectioned and stained for histological analysis. During lactation, HT cows produced 4 kg less colostrum and 3.7 kg less milk compared with CL cows. Lactating mammary gland microstructure was impacted after exposure to dry period heat stress; HT cows had fewer alveoli and a higher proportion of connective tissue in the mammary gland relative to CL cows, however alveolar area was similar between treatments. Rates of mammary epithelial cell proliferation and apoptosis were similar between treatment groups. This suggests that heat stress exposure during the dry period leads to reductions in milk yield that could be caused, in part, by a reduction in alveoli number in the lactating mammary gland but not to dynamic alterations in cellular turnover once lactation is established.

ObjectiveIncreasing evidence purports exercise as a first-line therapeutic for the treatment of nearly all forms of chronic pain. However, knowledge of efficacious dosing respective to treatment modality and pain condition is virtually absent in the literature. The purpose of this analysis was to calculate the extent to which exercise treatment shows dose-dependent effects similar to what is seen with pharmacological treatments.MethodsA recently published comprehensive review of exercise and physical activity for chronic pain in adults was identified in May 2017. This report reviewed different physical activity and exercise interventions and their effectiveness in reducing pain severity and found overall modest effects of exercise in the treatment of pain. We analyzed this existing data set, focusing specifically on the dose of exercise intervention in these studies. We re-analyzed data from 75 studies looking at benefits of time of exercising per week, frequency of exercise per week, duration of intervention (in weeks), and estimated intensity of exercise.ResultsAnalysis revealed a significant positive correlation with exercise duration and analgesic effect on neck pain. Multiple linear regression modeling of these data predicted that increasing the frequency of exercise sessions per week is most likely to have a positive effect on chronic pain patients.DiscussionModest effects were observed with one significant correlation between duration and pain effect for neck pain. Overall, these results provide insufficient evidence to conclude the presence of a strong dose effect of exercise in pain, but our modeling data provide tes predictions that can be used to design future studies to explicitly test the question of dose in specific patient populations.

BackgroundContact networks can be used to assess disease spread potential within a population. However, the data required to generate the networks can be challenging to collect. One method of collecting this type of data is by using radio-frequency identification (RFID) tags. The OpenBeacon RFID system generally consists of tags and readers. Communicating tags should be within 10m of the readers, which are powered by an external power source. The readers are challenging to implement in agricultural settings due to the lack of a power source and the large area needed to be covered.MethodsOpenBeacon firmware was modified to use the tag's onboard flash memory for data storage. The tags were deployed within an equine facility for a 7-day period. Tags were attached to the horses' halters, worn by facility staff, and placed in strategic locations around the facility to monitor which participants had contact with the specified locations during the study period. When the tags came within 2m of each other, they recorded the contact event participant IDs, and start and end times. At the end of the study period, the data were downloaded to a computer and analyzed using network analysis methods.ResultsThe resulting networks were plausible given the facility schedule as described in a survey completed by the facility manager. Furthermore, changes in the daily facility operations as described in the survey were reflected in the tag-collected data. In terms of the battery life, 88% of batteries maintained a charge for at least 6 days. Lastly, no consistent trends were evident in the horses' centrality metrics.DiscussionThis study demonstrates the utility of RFID tags for the collection of equine contact data. Future work should include the collection of contact data from multiple equine facilities to better characterize equine disease spread potential in Ontario.

The Rho and Ras pathways play vital roles in cell growth, division and motility. Cross-talk between the pathways amplifies their roles in cell proliferation and motility and its dysregulation is involved in disease pathogenesis. One important interaction for cross-talk occurs between p120RasGAP (RASA1), a GTPase activating protein (GAP) for Ras, and p190RhoGAP (p190RhoGAP-A, ARHGAP35), a GAP for Rho. The binding of these proteins is primarily mediated by two SH2 domains within p120RasGAP engaging phosphorylated tyrosines of p190RhoGAP, of which the best studied is pTyr-1105. To better understand the interaction between p120RasGAP and p190RhoGAP, we determined the 1.75 Å X-ray crystal structure of the N-terminal SH2 domain of p120RasGAP in the unliganded form, and its 1.6 Å co-crystal structure in complex with a synthesized phosphotyrosine peptide, EEENI(p-Tyr)SVPHDST, corresponding to residues 1100-1112 of p190RhoGAP. We find that the N-terminal SH2 domain of p120RhoGAP has the characteristic SH2 fold encompassing a central beta-sheet flanked by two alpha-helices, and that peptide binding stabilizes specific conformations of the βE-βF loop and arginine residues R212 and R231. Site-directed mutagenesis and native gel shifts confirm phosphotyrosine binding through the conserved FLVR motif arginine residue R207, and isothermal titration calorimetry finds a dissociation constant of 0.3 ± 0.1 μM between the phosphopeptide and SH2 domain. These results demonstrate that the major interaction between two important GAP proteins, p120RasGAP and p190RhoGAP, is mediated by a canonical SH2-pTyr interaction.