Deformations of nearly Kähler instantons

We formulate the deformation theory for instantons on nearly Kähler six-manifolds using spinors and Dirac operators. Using this framework we identify the space of deformations of an irreducible instanton with semisimple structure group with the kernel of an elliptic operator, and prove that abelian instantons are rigid. As an application, we show that the canonical connection on three of the four homogeneous nearly Kähler six-manifolds G/H is a rigid instanton with structure group H. In contrast, these connections admit large spaces of deformations when regarded as instantons on the tangent bundle with structure group SU(3)

Endocrine Therapy Nonadherence and Discontinuation in Black and White Women

Background: Differential use of endocrine therapy (ET) by race may contribute to breast cancer outcome disparities, but racial differences in ET behaviors are poorly understood. Methods: Women aged 20-74 years with a first primary, stage I-III, hormone receptor-positive (HR+) breast cancer were included. At 2 years postdiagnosis, we assessed nonadherence, defined as not taking ET every day or missing more than two pills in the past 14 days, discontinuation, and a composite measure of underuse, defined as either missing pills or discontinuing completely. Using logistic regression, we evaluated the relationship between race and nonadherence, discontinuation, and overall underuse in unadjusted, clinically adjusted, and socioeconomically adjusted models. Results: A total of 1280 women were included; 43.2% self-identified as black. Compared to white women, black women more often reported nonadherence (13.7% vs 5.2%) but not discontinuation (10.0% vs 10.7%). Black women also more often reported the following: hot flashes, night sweats, breast sensitivity, and joint pain; believing that their recurrence risk would not change if they stopped ET; forgetting to take ET; and cost-related barriers. In multivariable analysis, black race remained statistically significantly associated with nonadherence after adjusting for clinical characteristics (adjusted odds ratio = 2.72, 95% confidence interval = 1.75 to 4.24) and after adding socioeconomic to clinical characteristics (adjusted odds ratio = 2.44, 95% confidence interval = 1.50 to 3.97) but was not independently associated with discontinuation after adjustment. Low recurrence risk perception and lack of a shared decision making were strongly predictive of ET underuse across races. Conclusions: Our results highlight important racial differences in ET-Adherence behaviors, perceptions of benefits/harms, and shared decision making that may be targeted with culturally tailored interventions

Associations of obesity and circulating insulin and glucose with breast cancer risk: a Mendelian randomization analysis.

BACKGROUND: In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear. METHODS: We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium. RESULTS: All sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p  =  5.09  ×  10-4], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p  =  4.02  ×  10-4), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p  =  5.05  ×  10-19) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p  =  9.22  ×  10-6). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2-h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer. CONCLUSIONS: We confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer

Down regulation of epidermal growth factor receptors in liver proliferation induced by a mixture of triiodothyronine, amino acids, glucagon, and heparin (TAGH).

This study investigated the mechanisms by which TAGH solution (a mixture of triiodothyronine, amino acids, glucagon, and heparin) induces DNA synthesis in hepatocytes in the liver of intact rats, with particular reference to events at the epidermal growth factor (EGF) receptor. Both partial hepatectomy and infusion of TAGH stimulated DNA synthesis at 24 hours and both procedures resulted in a reduction of EGF receptors assessed in plasma membranes isolated from rat liver at this time. In cell cultures, while EGF strongly stimulated DNA synthesis and started EGF receptor down regulation, TAGH had only a minor effect (1.5 x basal) on DNA synthesis and did not interact with or down regulate the EGF receptor. Membrane phosphorylation studies, however, showed that TAGH induced phosphorylation of tyrosine residues in the EGF receptor. The in vivo action of TAGH seems to entail recruitment of similar changes in the EGF receptor to those that occur after partial hepatectomy

Effect of Invivo Administration of An Antibody to Epidermal Growth-Factor On the Rapid Increase in Dna-Synthesis Induced by Partial-Hepatectomy in the Rat

Recent reports indicate that transforming growth factor alpha (TGF-alpha) is produced within the fiver and acts as the natural ligand of the epidermal growth factor (EGF) receptor causing the EGF receptor down regulation and the hepatocyte proliferation observed after partial hepatectomy. The reported phenomenon that an antibody to EGF inhibits the regenerative response to partial hepatectomy was therefore re-investigated. The IgG fraction of an anti-rat EGF antibody was injected intravenously at the time of partial hepatectomy, and its effects on regenerative DNA synthesis were compared with those of non-immune IgG. Injection of IgG reduced the DNA synthetic response to partial hepatectomy, assessed 24 hours after resection by H-3-thymidine incorporation, but the effects of normal and anti-EGF IgG were not statistically different, despite the presence of excess anti-EGF IgG in the circulation throughout the experimental period. However, anti-EGF IgG could completely block the proliferative response of hepatocytes in culture to EGF. These results support the suggestion that EGF is not the major mediator of hepatocyte DNA synthesis in the early stages of liver regeneration

Lay food and health worker involvement in community nutrition and dietetics in England: roles, responsibilities and relationship with professionals

Background- Community-based food initiatives have developed in recent years with the aim of engaging previously 'hard to reach' groups. Lay workers engaged in community nutrition activities are promoted as a cost-effective mechanism for reaching underserved groups. The main objective of the study was to explore perceptions and definitions of lay food and health worker (LFHW) helping roles within the context of National Health Service (NHS) community nutrition and dietetic services in order to define the conceptual and practical elements of this new role and examine the interface with professional roles. Findings - Narratives from both professionals and LFHWs indicated that the primary role for LFHWs was to encourage dietary change by translating complex messages into credible and culturally appropriate advice. Conclusions - The primary role of LFHWs in the 15 projects involved was to support existing NHS services to promote healthy eating amongst 'hard to reach' communities. The activities undertaken by LFHWs are strongly influenced by professionals and the NHS. Inherent to this is a fairly narrow interpretation of health, resulting in a limited range of practice