Growth and Reproductive Development of Male Piglets Are More Vulnerable to Midgestation Maternal Stress Than That of Female Piglets

In many mammalian species, prenatal stress masculinizes female and feminizes male offspring impairing their reproductive capacity. Regrouping gestating sows is a common, stressful production practice, but its impact on the developing pigs of the sow is not fully known. This study examined the effects of regrouping gestating sows and the administration of exogenous glucocorticoids on the growth and external reproductive morphology of pigs. At 37.2 ± 0.26 d of gestation, 6 cohorts of 18 sows (N = 108) were placed in 1 of 3 treatments: socially stable (Stable), hydrocortisone acetate (HCA), or mixed (Mixed). The HCA sows were administered 70 mg HCA, a synthetic glucocorticoid, twice daily during the 21 d experimental period. Each Mixed sow was penned with 2 companion sows (Companion) and regrouped on d 7 and 14 with 2 different Companion sows in a new pen. Stable and HCA sows were penned in treatment groups of 3 sows. Sow social rank was assessed weekly during feeding. After the 21 d experimental period, all sows were housed in gestation stalls for the duration of pregnancy. During the 21 d, Companion sows gained more weight than HCA and Mixed sows (P \u3c 0.05) with Stable sows intermediate. High ranked sows gained more weight than middle and low ranked sows (P \u3c 0.05). Mixed sows had greater head lesion scores than Stable and HCA sows (P \u3c 0.05) with Companion sows intermediate. Head lesions increased with lower social rank (P \u3c 0.001). Sow treatment did not affect farrowing rate, litter size, or sex ratio (P \u3e 0.10). Social rank also had no effect on farrowing rate (P \u3e 0.10), but affected total litter size (P = 0.03). High ranked sows bore and weaned more live females than low ranked sows (P \u3c 0.05), in part due to differential preweaning mortality among female pigs (P = 0.01). Only male pigs were affected by sow treatment. Preweaning mortality was higher among male pigs from HCA than from Mixed sows (P = 0.04) with other treatments intermediate. Despite no weight differences in the preweaning period, at 160 d of age males from HCA sows weighed more than males from Stable sows (P = 0.01) with other treatments intermediate. Males born to Companion sows had longer relative anogenital distances, a marker of fetal testosterone exposure, than males from Mixed sows (P = 0.03) with other treatments intermediate. The prenatal environment affected the pigs in a sex-specific manner altering the growth and reproductive morphology of the males more than that of the females

Leukocyte function and health status of calves supplemented with vitamins A and E

Forty-four Holstein calves were fed milk replacers with varied concentrations of vitamins A and E from 3 to 45 d of age to determine their effects on concentrations of plasma vitamin A (retinol and retinyl palmitate) and vitamin E (a- tocopherol), lymphocyte and neutrophil functions, and health of calves. Plasma a-tocopherol was unaffected by increased vitamin A supplementation. Fecal scores, and eye and nose membrane responses were improved with increased vitamin A and lower vitamin E concentration, whereas the same treatment tended to reduce neutrophil cytotoxic and bactericidal activity by 6 wk of age. Increased supplemental vitamin E tended to enhance neutrophil functions. However, age appeared to have an effect on response to both vitamins

Patient-reported outcome instruments used in immune-checkpoint inhibitor clinical trials in oncology: a systematic review.

Immune-checkpoint inhibitors (ICI) have shown significant benefits for overall survival across various cancer types. Patient-reported outcomes (PROs) are assessed in clinical trials as a measure of efficacy. However, it remains unclear to what extent current PRO instruments capture symptoms specific to ICI toxicities. We conducted a systematic review to identify the use and content validity of PRO instruments in ICI clinical trials in oncology. Literature was retrieved from PubMed, Embase, PsycINFO, Medline and CINAHL databases. Articles presenting ICI clinical trials' PRO results, clinical trial study protocols, and conference abstracts stating the use of PRO measures were assessed. We evaluated the validity of identified instruments by comparing their symptom-related content with the adverse events reported in each ICI clinical trial. From database inception until January 2020, we identified 191 ICI clinical trials stating the use of PRO measures of which 26 published PRO results. The cancer-specific EORTC QLQ-C30 and the generic EQ-5D questionnaires were the most widely used instruments, often in combination with disease-specific PROs. Instruments used to report PRO symptom-related toxicities covered 45% of the most frequently reported AEs, whereas 23% of AEs were partially covered and 29% were not covered at all. Of non-covered AEs, 59% referred to the dermatologic system. Partially covered AEs related to endocrine and specific types of pain. Despite the high frequency of symptom-related toxicities related to ICI, these events are only partially covered (or not addressed) by current PRO instruments, even when combined. Further research is needed to develop new strategies to tailor PRO instruments to specific ICI toxicities

Associations of Prenatal Nicotine Exposure and the Dopamine Related Genes ANKK1 and DRD2 to Verbal Language

Language impairment (LI) and reading disability (RD) are common pediatric neurobehavioral disorders that frequently co-occur, suggesting they share etiological determinants. Recently, our group identified prenatal nicotine exposure as a factor for RD and poor reading performance. Using smoking questionnaire and language data from the Avon Longitudinal Study of Parents and Children, we first determined if this risk could be expanded to other communication disorders by evaluating whether prenatal nicotine exposure increases risk for LI and poor performance on language tasks. Prenatal nicotine exposure increased LI risk (OR = 1.60; p = 0.0305) in a dose-response fashion with low (OR = 1.25; p = 0.1202) and high (OR = 3.84; p = 0.0002) exposures. Next, hypothesizing that the effects of prenatal nicotine may also implicate genes that function in nicotine related pathways, we determined whether known nicotine dependence (ND) genes associate with performance on language tasks. We assessed the association of 33 variants previously implicated in ND with LI and language abilities, finding association between ANKK1/DRD2 and performance on language tasks (p≤0.0003). The associations of markers within ANKK1 were replicated in a separate LI case-control cohort (p<0.05). Our results show that smoking during pregnancy increases the risk for LI and poor performance on language tasks and that ANKK1/DRD2 contributes to language performance. More precisely, these findings suggest that prenatal environmental factors influence in utero development of neural circuits vital to language. Our association of ANKK1/DRD2 further implicates the role of nicotine-related pathways and dopamine signaling in language processing, particularly in comprehension and phonological memory

A Heuristic Image Search Algorithm for Active Shape Model Segmentation of the Caudate Nucleus and Hippocampus in Brain MR Images of Children with FASD

Magnetic Resonance Imaging provides a non-invasive means to study the neural correlates of Fetal Alcohol Spectrum Disorder (FASD) - the most common form of preventable mental retardation worldwide. One approach aims to detect brain abnormalities through an assessment of volume and shape of two sub-cortical structures, the caudate nucleus and hippocampus. We present a method for automatically segmenting these structures from high-resolution MR images captured as part of an ongoing study into the neural correlates of FASD. Our method incorporates an Active Shape Model, which is used to learn shape variation from manually segmented training data. A modified discrete Geometrically Deformable Model is used to generate point correspondence between training models. An ASM is then created from the landmark points. Experiments were conducted on the image search phase of ASM segmentation, in order to find the technique best suited to segmentation of the hippocampus and caudate nucleus. Various popular image search techniques were tested, including an edge detection method and a method based on grey profile Mahalanobis distance measurement. A novel heuristic image search method was also developed and tested. This heuristic method improves image segmentation by taking advantage of characteristics specific to the target data, such as a relatively homogeneous tissue colour in target structures. Results show that ASMs that use the heuristic image search technique produce the most accurate segmentations. An ASM constructed using this technique will enable researchers to quickly, reliably, and automatically segment test data for use in the FASD study

Organization of Multinational Activities and Ownership Structure

We develop a model in which multinational investors decide about the modes of organization, the locations of production, and the markets to be served. Foreign investments are driven by market-seeking and cost-reducing motives. We further assume that investors face costs of control that vary among sectors and increase in distance. The results show that (i) production intensive sectors are more likely to operate a foreign business independent of the investment motive, (ii) that distance may have a non-monotonous effect on the likelihood of horizontal investments, and (iii) that globalization, if understood as reducing distance, leads to more integration

The M33 Variable Star Population Revealed by Spitzer

We analyze five epochs of Spitzer Space Telescope/Infrared Array Camera (IRAC) observations of the nearby spiral galaxy M33. Each epoch covered nearly a square degree at 3.6, 4.5, and 8.0 microns. The point source catalog from the full dataset contains 37,650 stars. The stars have luminosities characteristic of the asymptotic giant branch and can be separated into oxygen-rich and carbon-rich populations by their [3.6] - [4.5] colors. The [3.6] - [8.0] colors indicate that over 80% of the stars detected at 8.0 microns have dust shells. Photometric comparison of epochs using conservative criteria yields a catalog of 2,923 variable stars. These variables are most likely long-period variables amidst an evolved stellar population. At least one-third of the identified carbon stars are variable.Comment: Accepted for publication in ApJ. See published article for full resolution figures and electronic table

Multipoint genome-wide linkage scan for nonword repetition in a multigenerational family further supports chromosome 13q as a locus for verbal trait disorders

Verbal trait disorders encompass a wide range of conditions and are marked by deficits in five domains that impair a person’s ability to communicate: speech, language, reading, spelling, and writing. Nonword repetition is a robust endophenotype for verbal trait disorders that is sensitive to cognitive processes critical to verbal development, including auditory processing, phonological working memory, and motor planning and programming. In the present study, we present a six-generation extended pedigree with a history of verbal trait disorders. Using genome-wide multipoint variance component linkage analysis of nonword repetition, we identified a region spanning chromosome 13q14–q21 with LOD = 4.45 between 52 and 55 cM, spanning approximately 5.5 Mb on chromosome 13. This region overlaps with SLI3, a locus implicated in reading disability in families with a history of specific language impairment. Our study of a large multigenerational family with verbal trait disorders further implicates the SLI3 region in verbal trait disorders. Future studies will further refine the specific causal genetic factors in this locus on chromosome 13q that contribute to language traits

Daily Dietary Intake Patterns Improve after Visiting a Food Pantry among Food-Insecure Rural Midwestern Adults.

Emergency food pantries provide food at no cost to low-resource populations. The purpose of this study was to evaluate single-day dietary intake patterns before and after visiting a food pantry among food-secure and food-insecure pantry clients. This observational cohort study comprised a paired, before-and-after design with a pantry visit as the intervention. Participants (n = 455) completed a demographic and food security assessment, and two 24-h dietary recalls. Adult food security was measured using the U.S. Household Food Security Survey Module. Dietary intake patterns were assessed using Automated Self-Administered 24-h Recall data and classified by Healthy Eating Index (HEI-2010) scores, dietary variety, number of eating occasions, and energy intake. Paired t-tests and Wilcoxon signed-rank tests compared outcomes before and after a pantry visit. Mean dietary variety increased after the pantry visit among both food-secure (p = 0.02) and food-insecure (p \u3c 0.0001) pantry clients. Mean energy intake (p = 0.0003), number of eating occasions (p = 0.004), and HEI-2010 component scores for total fruit (p \u3c 0.001) and whole fruit (p \u3c 0.0003) increased among food-insecure pantry clients only. A pantry visit may improve dietary intake patterns, especially among food-insecure pantry clients

Statistical Mechanics of Glass Formation in Molecular Liquids with OTP as an Example

We extend our statistical mechanical theory of the glass transition from examples consisting of point particles to molecular liquids with internal degrees of freedom. As before, the fundamental assertion is that super-cooled liquids are ergodic, although becoming very viscous at lower temperatures, and are therefore describable in principle by statistical mechanics. The theory is based on analyzing the local neighborhoods of each molecule, and a statistical mechanical weight is assigned to every possible local organization. This results in an approximate theory that is in very good agreement with simulations regarding both thermodynamical and dynamical properties