High Educational Aspirations Among Pregnant Adolescents Are Related to Pregnancy Unwantedness and Subsequent Parenting Stress and Inadequacy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106966/1/jomf12103.pd

Diet of the Golden Jackal (Canis aureus) and Silver-Backed Jackal (Canis mesomelas) in the Southern Part of the Serengeti Ecosystem, Tanzania: A Comparative Study

Habitat and food resource partitioning are predicted to facilitate the coexistence of similar-sized carnivores. The golden jackal (Canis aureus) and silver-backed jackal (Canis mesomelas) are similar-sized canids that respectively inhabit grassland and woodland in the Serengeti ecosystem, Tanzania. As information on the diet and food-intake of these two species in this ecosystem is limited, we aimed to compare the diet and food-intake of these canids in the wet and dry seasons, using data from focal samples of foraging behaviour and scat analysis. We predicted dietary differences between these species, seasonal differences within species and peak food intake when breeding. Result of a logistic regression considering insect and small mammal remains in scats revealed dietary differences both between species and within-species seasonal differences. Results of a censored regression model on the estimated weigh of food intake by foraging individuals indicated that intake was highest during the breeding season of each species, which occurs in the wet season in golden jackals and the dry-season in silver-backed jackals. Our study provides new insights on differences in the foraging ecology of these two jackal species in the Serengeti ecosystem. Keywords:    Canis aureus; Canis mesomelas, diet, Serengeti ecosystem, season

Sensitive Periods for Psychosocial Risk in Childhood and Adolescence and Cardiometabolic Outcomes in Young Adulthood

Greater psychosocial risk in childhood and adolescence predicts poorer cardiometabolic outcomes in adulthood. We assessed whether the timing of psychosocial risk from infancy through adolescence predicts cardiometabolic outcomes in young adulthood. Young adults and their mothers participated in a longitudinal study beginning in infancy in Santiago, Chile (N = 1040). At infancy, 5 years, 10 years, and adolescence, mothers reported on depressive symptoms, stressful experiences, support for child development in the home, father absence, parental education, and socioeconomic status (SES) to create a psychosocial risk composite at each time point. Young adults (52.1% female; 21–27 years) provided fasting serum samples and participated in anthropometric and blood pressure (BP) assessments, including a dualenergy X-ray absorptiometry (DXA) scan for measuring body fat. Greater infant psychosocial risk was associated with a greater young adult metabolic syndrome score (β = 0.07, 95% confidence intervals (CI): 0.01 to 0.13, p = 0.02), a higher body mass index and waist circumference composite (β = 0.08, 95% CI: 0.03 to 0.13, p = 0.002), and a higher body fat (DXA) composite (β = 0.07, 95% CI: 0.01 to 0.12, p = 0.02). No psychosocial risk measure from any time point was associated with BP. Infant psychosocial risk predicted cardiometabolic outcomes in young adulthood better than psychosocial risk at 5 years, 10 years, or adolescence, mean of psychosocial risk from infancy through adolescence, and maximum of psychosocial risk at any one time. Consistent with the Developmental Origins of Health and Disease model, findings suggest that infancy is a sensitive period for psychosocial risk leading to poorer cardiometabolic outcomes in young adulthood

Mitochondrial Respiratory Capacity and Content Are Normal in Young Insulin-Resistant Obese Humans

Considerable debate exists about whether alterations in mitochondrial respiratory capacity and/or content play a causal role in the development of insulin resistance during obesity. The current study was undertaken to determine whether such alterations are present during the initial stages of insulin resistance in humans. Young (∼23 years) insulin-sensitive lean and insulin-resistant obese men and women were studied. Insulin resistance was confirmed through an intravenous glucose tolerance test. Measures of mitochondrial respiratory capacity and content as well as H(2)O(2) emitting potential and the cellular redox environment were performed in permeabilized myofibers and primary myotubes prepared from vastus lateralis muscle biopsy specimens. No differences in mitochondrial respiratory function or content were observed between lean and obese subjects, despite elevations in H(2)O(2) emission rates and reductions in cellular glutathione. These findings were apparent in permeabilized myofibers as well as in primary myotubes. The results suggest that reductions in mitochondrial respiratory capacity and content are not required for the initial manifestation of peripheral insulin resistance

Attitudes toward cost-conscious care among U.S. physicians and medical students: analysis of national cross-sectional survey data by age and stage of training

Abstract Background The success of initiatives intended to increase the value of health care depends, in part, on the degree to which cost-conscious care is endorsed by current and future physicians. This study aimed to first analyze attitudes of U.S. physicians by age and then compare the attitudes of physicians and medical students. Methods A paper survey was mailed in mid-2012 to 3897 practicing physicians randomly selected from the American Medical Association Masterfile. An electronic survey was sent in early 2015 to all 5,992 students at 10 U.S. medical schools. Survey items measured attitudes toward cost-conscious care and perceived responsibility for reducing healthcare costs. Physician responses were first compared across age groups (30–40 years, 41–50 years, 51–60 years, and > 60 years) and then compared to student responses using Chi square tests and logistic regression analyses (controlling for sex). Results A total of 2,556 physicians (65%) and 3395 students (57%) responded. Physician attitudes generally did not differ by age, but differed significantly from those of students. Specifically, students were more likely than physicians to agree that cost to society should be important in treatment decisions (p < 0.001) and that physicians should sometimes deny beneficial but costly services (p < 0.001). Students were less likely to agree that it is unfair to ask physicians to be cost-conscious while prioritizing patient welfare (p < 0.001). Compared to physicians, students assigned more responsibility for reducing healthcare costs to hospitals and health systems (p < 0.001) and less responsibility to lawyers (p < 0.001) and patients (p < 0.001). Nearly all significant differences persisted after controlling for sex and when only the youngest physicians were compared to students. Conclusions Physician attitudes toward cost-conscious care are similar across age groups. However, physician attitudes differ significantly from medical students, even among the youngest physicians most proximate to students in age. Medical student responses suggest they are more accepting of cost-conscious care than physicians and attribute more responsibility for reducing costs to organizations and systems rather than individuals. This may be due to the combined effects of generational differences, new medical school curricula, students’ relative inexperience providing cost-conscious care within complex healthcare systems, and the rapidly evolving U.S. healthcare system.https://deepblue.lib.umich.edu/bitstream/2027.42/146517/1/12909_2018_Article_1388.pd

FOXA1 and adaptive response determinants to HER2 targeted therapy in TBCRC 036

Inhibition of the HER2/ERBB2 receptor is a keystone to treating HER2-positive malignancies, particularly breast cancer, but a significant fraction of HER2-positive (HER2+) breast cancers recur or fail to respond. Anti-HER2 monoclonal antibodies, like trastuzumab or pertuzumab, and ATP active site inhibitors like lapatinib, commonly lack durability because of adaptive changes in the tumor leading to resistance. HER2+ cell line responses to inhibition with lapatinib were analyzed by RNAseq and ChIPseq to characterize transcriptional and epigenetic changes. Motif analysis of lapatinib-responsive genomic regions implicated the pioneer transcription factor FOXA1 as a mediator of adaptive responses. Lapatinib in combination with FOXA1 depletion led to dysregulation of enhancers, impaired adaptive upregulation of HER3, and decreased proliferation. HER2-directed therapy using clinically relevant drugs (trastuzumab with or without lapatinib or pertuzumab) in a 7-day clinical trial designed to examine early pharmacodynamic response to antibody-based anti-HER2 therapy showed reduced FOXA1 expression was coincident with decreased HER2 and HER3 levels, decreased proliferation gene signatures, and increased immune gene signatures. This highlights the importance of the immune response to anti-HER2 antibodies and suggests that inhibiting FOXA1-mediated adaptive responses in combination with HER2 targeting is a potential therapeutic strategy

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine