Spectropolarimetric observations of the transiting planetary system of the K dwarf HD 189733

With a Jupiter-mass planet orbiting at a distance of only 0.031 AU, the active K2 dwarf HD 189733 is a potential candidate in which to study the magnetospheric interactions of a cool star with its recently-discovered close-orbiting giant planet. We decided to explore the strength and topology of the large-scale magnetosphere of HD 189733, as a future benchmark for quantitative studies for models of the star/planet magnetic interactions. To this end, we used ESPaDOnS, the new generation spectropolarimeter at the Canada-France-Hawaii 3.6m telescope, to look for Zeeman circular polarisation signatures in the line profiles of HD 189733 in 2006 June and August. Zeeman signatures in the line profiles of HD 189733 are clearly detected in all spectra, demonstrating that a field is indeed present at the surface of the star. The Zeeman signatures are not modulated with the planet's orbital period but apparently vary with the stellar rotation cycle. The reconstructed large-scale magnetic field, whose strength reaches a few tens of G, is significantly more complex than that of the Sun; it involves in particular a significant toroidal component and contributions from magnetic multipoles of order up to 5. The CaII H & K lines clearly feature core emission, whose intensity is apparently varying mostly with rotation phase. Our data suggest that the photosphere and magnetic field of HD 189733 are sheared by a significant amount of differential rotation. Our initial study confirms that HD 189733 is an optimal target for investigating activity enhancements induced by closely orbiting planets. More data are needed, densely covering both the orbital and rotation cycles, to investigate whether and how much the planet contributes to the overall activity level of HD 189733.Comment: Accepted in Astronomy and Astrophysics, 12 page

Use of a new proximity assay (NanoBRET) to investigate the ligand binding characteristics of three fluorescent ligands to the human β1-adrenoceptor expressed in HEK-293 cells

Previous research has indicated that allosteric interactions across the dimer interface of β1-adrenoceptors may be responsible for a secondary low affinity binding conformation. Here we have investigated the potential for probe dependence, in the determination of antagonist pKi values at the human β1-adenoceptor, which may result from such allosterism interactions. Three fluorescent β1-adrenoceptor ligands were used to investigate this using bioluminescence energy transfer (BRET) between the receptor-bound fluorescent ligand and the N-terminal NanoLuc tag of a human β1-adrenoceptor expressed in HEK 293 cells (NanoBRET). This proximity assay showed high affinity specific binding to the NanoLuc-β1-adrenoceptor with each of the three fluorescent ligands yielding KD values of 87.1 ± 10nM (n=8), 38.1 ± 12nM (n=7), 13.4 ± 2nM (n=14) for propranolol-Peg8-BY630, propranolol-3(Ala-Ala)-BY630 and CGP-12177- TMR respectively. Parallel radioligand-binding studies with 3H-CGP12177 and TIRF microscopy, to monitor NanoLuc bioluminescence, confirmed a high cell surface expression of the NanoLuc- 31-adrenoceptor in HEK 293 cells (circa 1500 fmol.mg protein-1). Following a 1h incubation with fluorescent ligands and β1-adrenoceptor competing antagonists, there were significant differences (p < 0.001) in the pKi values obtained for CGP20712a and CGP 12177 with the different fluorescent ligands and 3H-CGP 12177. However, increasing the incubation time to 2h removed these significant differences. The data obtained show that the NanoBRET assay can be applied successfully to study ligand-receptor interactions at the human β1-adrenoceptor. However, the study also emphasizes the importance of ensuring that both the fluorescent and competing ligands are in true equilibrium before interpretations regarding probe dependence can be made

Inulin oligofructose attenuates metabolic syndrome in high-carbohydrate, high-fat diet-fed rats

Prebiotics alter bacterial content in the colon, and therefore could be useful for obesity management. We investigated the changes following addition of inulin oligofructose (IO) in the food of rats fed either a corn starch (C) diet or a high-carbohydrate, high-fat (H) diet as a model of diet-induced metabolic syndrome. IO did not affect food intake, but reduced body weight gain by 5·3 and 12·3 % in corn starch+inulin oligofructose (CIO) and high-carbohydrate, high-fat with inulin oligofructose (HIO) rats, respectively. IO reduced plasma concentrations of free fatty acids by 26·2 % and TAG by 75·8 % in HIO rats. IO increased faecal output by 93·2 %, faecal lipid excretion by 37·9 % and weight of caecum by 23·4 % and colon by 41·5 % in HIO rats. IO improved ileal morphology by reducing inflammation and improving the density of crypt cells in HIO rats. IO attenuated H diet-induced increases in abdominal fat pads (C 275 (sem 19), CIO 264 (sem 40), H 688 (sem 55), HIO 419 (sem 32) mg/mm tibial length), fasting blood glucose concentrations (C 4·5 (sem 0·1), CIO 4·2 (sem 0·1), H 5·2 (sem 0·1), HIO 4·3 (sem 0·1) mmol/l), systolic blood pressure (C 124 (sem 2), CIO 118 (sem 2), H 152 (sem 2), HIO 123 (sem 3) mmHg), left ventricular diastolic stiffness (C 22·9 (sem 0·6), CIO 22·9 (sem 0·5), H 27·8 (sem 0·5), HIO 22·6 (sem 1·2)) and plasma alanine transaminase (C 29·6 (sem 2·8), CIO 32·1 (sem 3·0), H 43·9 (sem 2·6), HIO 33·6 (sem 2·0) U/l). IO attenuated H-induced increases in inflammatory cell infiltration in the heart and liver, lipid droplets in the liver and plasma lipids as well as impaired glucose and insulin tolerance. These results suggest that increasing soluble fibre intake with IO improves signs of the metabolic syndrome by decreasing gastrointestinal carbohydrate and lipid uptake

The Mississippi delta health collaborative medication therapy management model: Public health and pharmacy working together to improve population health in the Mississippi delta

© 2020. Introduction The Mississippi Delta has high rates of chronic disease and is known for its poor health outcomes and health disparities. University of Mississippi School of Pharmacy (UMSOP) and the Mississippi State Department of Health partnered in 2009 through the Mississippi Delta Health Collaborative to reduce health disparities and improve clinical outcomes by expanding the UMSOP\u27s evidence-based medication therapy management (MTM) initiative, focused in Mississippi\u27s 18-county Delta region, to federally qualified health centers (FQHCs) in 4 of those counties. Methods Between January 2009 and August 2018, the MTM initiative targeted FQHC patients aged 18 years or older with a diagnosis of diabetes, hypertension, and/or dyslipidemia. Pharmacists initially met face-to-face with patients to review all medications, provide education about chronic diseases, identify and resolve drug therapy problems, and take appropriate actions to help improve the effectiveness of medication therapies. Clinical parameters evaluated were systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and hemoglobin A1c (HbA1c). Results The analysis included 335 patients with hypertension (n = 287), dyslipidemia (n = 131), and/or diabetes (n = 331). Significant mean reductions occurred in the following metrics: SBP (7.1 mm Hg), DBP (6.3 mm Hg), LDL cholesterol (24.9 mg/dL), triglycerides (45.5 mg/dL), total cholesterol (37.7 mg/dL), and HbA1c (1.6% [baseline ≥6%] and 1.9% [baseline ≥9%]). Conclusion Despite the cultural and environmental disadvantages present in the Mississippi Delta, the integrated MTM treatment program demonstrated significant health improvements across 3 chronic diseases: hypertension, dyslipidemia, and diabetes. This model demonstrates that a partnership between public health and pharmacy is a successful and innovative approach to care

Daily mood, partner support, sexual interest, and sexual activity among adolescent women

This is a post print version of the article. The official published version can be accessed from the link below.Objective: to examine day-to-day associations of coitus, sexual interest, partner emotional support, negative mood and positive mood among adolescent women. Methods: Women (ages 14 – 17 at enrollment; N=146) enrolled from one of three adolescent primary care clinics completed up to five 84-day diaries over a 27-month period. The diaries assessed partner interactions, sexual activity, substance use and mood. Partner-specific measures assessed on each day included partner emotional support (4 items; alpha = 0.94), argument with a partner (no/yes) and coitus (no/yes). Within-day measures assessed marijuana use (no/yes), Positive Mood (3-items; alpha = 0. 86); Negative Mood (3-items; alpha = 0.82) and Sexual Interest (1-item). Lagged measures of mood and sexual activity were included in multivariate models to control for recent mood and sexual behavior effects on current day mood and coitus. Two main analyses were conducted: coitus as a predictor of positive and negative mood; and the role of positive and negative mood as predictors of coitus. Analyses were conducted by multivariate mixed effect regression and mixed effect logistic regression models. Results: Data represent 28,376 days from 146 participants. The average number of diary days was 194 days per participant. Sexual activity was reported on 8.3% of days, with condoms used for 27.0% of these coital events. Marijuana was used on 11% of days. Significant predictors of positive mood on a given day included partner support, marijuana use, and coitus. Negative mood was associated with having an argument with a partner and with prior day coitus. Predictors of coitus on a given day included age (Odds ratio = 1.22), increased coital frequency in previous week (OR = 1.49), coitus on the previous day (1.21), increased same-day sexual interest (OR = 2.8) and decreased same-day negative mood (OR = 0.92). Conclusions: The data demonstrate complex associations of sexual interest, mood, partner interactions and sexual activity

GALA: an international multicentre randomised trial comparing general anaesthesia versus local anaesthesia for carotid surgery

Background: Patients who have severe narrowing at or near the origin of the internal carotid artery as a result of atherosclerosis have a high risk of ischaemic stroke ipsilateral to the arterial lesion. Previous trials have shown that carotid endarterectomy improves long-term outcomes, particularly when performed soon after a prior transient ischaemic attack or mild ischaemic stroke. However, complications may occur during or soon after surgery, the most serious of which is stroke, which can be fatal. It has been suggested that performing the operation under local anaesthesia, rather than general anaesthesia, may be safer. Therefore, a prospective, randomised trial of local versus general anaesthesia for carotid endarterectomy was proposed to determine whether type of anaesthesia influences peri-operative morbidity and mortality, quality of life and longer term outcome in terms of stroke-free survival. Methods/design: A two-arm, parallel group, multicentre randomised controlled trial with a recruitment target of 5000 patients. For entry into the study, in the opinion of the responsible clinician, the patient requiring an endarterectomy must be suitable for either local or general anaesthesia, and have no clear indication for either type. All patients with symptomatic or asymptomatic internal carotid stenosis for whom open surgery is advised are eligible. There is no upper age limit. Exclusion criteria are: no informed consent; definite preference for local or general anaesthetic by the clinician or patient; patient unlikely to be able to co-operate with awake testing during local anaesthesia; patient requiring simultaneous bilateral carotid endarterectomy; carotid endarterectomy combined with another operation such as coronary bypass surgery; and, the patient has been randomised into the trial previously. Patients are randomised to local or general anaesthesia by the central trial office. The primary outcome is the proportion of patients alive, stroke free ( including retinal infarction) and without myocardial infarction 30 days post-surgery. Secondary outcomes include the proportion of patients alive and stroke free at one year; health related quality of life at 30 days; surgical adverse events, re-operation and re-admission rates; the relative cost of the two methods of anaesthesia; length of stay and intensive and high dependency bed occupancy

Relationship of vascular maturation in breast cancer blood vessels to vascular density and metastasis, assessed by expression of a novel basement membrane component, LH39

Angiogenesis, the formation of new vessels, has been demonstrated to be an indicator of prognosis in breast cancer patients. The extent of differentiation of the tumour vessels may affect access of peripheral white cells and egress or invasion of tumour cells. This has not been assessed in relation to tumour microvessel density or other variables and may be a marker of vascular remodelling. LH39 is a monoclonal antibody recognizing an epitope located at the lamina lucida of mature small veins and capillaries but not in newly formed vessels. To study vascular differentiation in breast tumours, we examined the vascular maturation index (VMI) in 12 normal and 50 breast carcinomas and this was correlated with different clinicopathological variables including angiogenesis. Mature vessels were defined by staining with antibodies to both LH39 and to CD31, using double immunohistochemistry, whereas immature vessels stained only for CD31. VMI was defined as the % fraction of mature vessels (LH39-positive) / total number of vessels (CD31-positive). The VMI was significantly higher in normal (54–68.5%; median 66.5%) than in tumours (0–47%; median 8.8%) (P = 0.0005). There was a significant inverse correlation between the tumour VMI and nodal status (Fisher's exact test, P = 0.01) and between high VMI and low thymidine phosphorylase (TP) expression (Mann–Whitney U -test, P = 0.01). No significant association between VMI and tumour size, oestrogen receptor, epidermal growth factor receptor, grade, angiogenesis, patient age, or E-selectin was seen. There was a significant reduction in relapse-free survival (P = 0.01) with high angiogenesis. These findings show that the VMI gives new information on the mechanism of tumour angiogenesis independently from microvessel quantitation, there is a wide variation in the differentiation of tumour vasculature but the degree of capillary differentiation is not associated with quantitative angiogenesis. The VMI identifies a subset of patients who have a high chance of regional node involvement. © 2000 Cancer Research Campaig

HIV-1 DNA Is Maintained in Antigen-Specific CD4+ T Cell Subsets in Patients on Long-Term Antiretroviral Therapy Regardless of Recurrent Antigen Exposure

Memory CD4+ T cells (mCD4s) containing integrated HIV DNA are considered the main barrier to a cure for HIV infection. Here, we analyzed HIV DNA reservoirs in antigen-specific subsets of mCDs to delineate the mechanisms by which HIV reservoirs persist during antiretroviral therapy (ART). HIV Gag, cytomegalovirus (CMV), and tetanus toxoid (TT)-specific mCD4s were isolated from peripheral blood samples obtained from 11 individual subjects, 2-11 years after commencing ART. Antigen-specific mCD4s were identified by the sensitive OX40 assay and purified by cell sorting. Total HIV DNA levels were quantified by real-time PCR, and clonal viral sequences generated from mCD4 subsets and pre-ART plasma samples. Quantitative results and sequence analysis were restricted to five and three study participants, respectively, which was likely due to the low frequency of the antigen-specific mCD4s and relatively low HIV DNA proviral loads. Median HIV Gag-, CMV-, and TT-specific mCD4s were 0.61%, 2.46%, and 0.78% of total mCD4s, and they contained a median of 2.50, 2.38, and 2.55 log 10 copies of HIV DNA per 10 6 cells, respectively. HIV DNA sequences were derived from antigen-specific mCD4s clustered with sequences derived from pre-ART plasma samples. There was a trend toward increased viral diversity in clonal viral sequences derived from CMV-specific mCD4s relative to TT-specific mCD4s. Despite limitations, this study provides direct evidence that HIV reservoirs persist in memory CD4+ T cell subsets maintained by homeostatic proliferation (TT) and adds to growing evidence against viral evolution during ART. Similar future studies require techniques that sample diverse HIV reservoirs and with improved sensitivity

Classification of hyperbolic Dynkin diagrams, root lengths and Weyl group orbits

We give a criterion for a Dynkin diagram, equivalently a generalized Cartan matrix, to be symmetrizable. This criterion is easily checked on the Dynkin diagram. We obtain a simple proof that the maximal rank of a Dynkin diagram of compact hyperbolic type is 5, while the maximal rank of a symmetrizable Dynkin diagram of compact hyperbolic type is 4. Building on earlier classification results of Kac, Kobayashi-Morita, Li and Sa\c{c}lio\~{g}lu, we present the 238 hyperbolic Dynkin diagrams in ranks 3-10, 142 of which are symmetrizable. For each symmetrizable hyperbolic generalized Cartan matrix, we give a symmetrization and hence the distinct lengths of real roots in the corresponding root system. For each such hyperbolic root system we determine the disjoint orbits of the action of the Weyl group on real roots. It follows that the maximal number of disjoint Weyl group orbits on real roots in a hyperbolic root system is 4.Comment: J. Phys. A: Math. Theor (to appear