A Prograde, Low-Inclination Orbit for the Very Hot Jupiter WASP-3b

We present new spectroscopic and photometric observations of the transiting exoplanetary system WASP-3. Spectra obtained during two separate transits exhibit the Rossiter-McLaughlin (RM) effect and allow us to estimate the sky-projected angle between the planetary orbital axis and the stellar rotation axis, lambda = 3.3^{+2.5}_{-4.4} degrees. This alignment between the axes suggests that WASP-3b has a low orbital inclination relative to the equatorial plane of its parent star. During our first night of spectroscopic measurements, we observed an unexpected redshift briefly exceeding the expected sum of the orbital and RM velocities by 140 m/s. This anomaly could represent the occultation of material erupting from the stellar photosphere, although it is more likely to be an artifact caused by moonlight scattered into the spectrograph.Comment: 23 pages, 4 figures, Accepted for publication in The Astrophysical Journal, Replacement includes revised citation

Planet Hunters VII. Discovery of a New Low-Mass, Low-Density Planet (PH3 c) Orbiting Kepler-289 with Mass Measurements of Two Additional Planets (PH3 b and d)

We report the discovery of one newly confirmed planet ($P=66.06$ days, $R_{\rm{P}}=2.68\pm0.17R_\oplus$) and mass determinations of two previously validated Kepler planets, Kepler-289 b ($P=34.55$ days, $R_{\rm{P}}=2.15\pm0.10R_\oplus$) and Kepler-289-c ($P=125.85$ days, $R_{\rm{P}}=11.59\pm0.10R_\oplus$), through their transit timing variations (TTVs). We also exclude the possibility that these three planets reside in a $1:2:4$ Laplace resonance. The outer planet has very deep ($\sim1.3$), high signal-to-noise transits, which puts extremely tight constraints on its host star's stellar properties via Kepler's Third Law. The star PH3 is a young ($\sim1$ Gyr as determined by isochrones and gyrochronology), Sun-like star with $M_*=1.08\pm0.02M_\odot$, $R_*=1.00\pm0.02R_\odot$, and $T_{\rm{eff}}=5990\pm38$ K. The middle planet's large TTV amplitude ($\sim5$ hours) resulted either in non-detections or inaccurate detections in previous searches. A strong chopping signal, a shorter period sinusoid in the TTVs, allows us to break the mass-eccentricity degeneracy and uniquely determine the masses of the inner, middle, and outer planets to be $M=7.3\pm6.8M_\oplus$, $4.0\pm0.9M_\oplus$, and $M=132\pm17M_\oplus$, which we designate PH3 b, c, and d, respectively. Furthermore, the middle planet, PH3 c, has a relatively low density, $\rho=1.2\pm0.3$ g/cm$^3$ for a planet of its mass, requiring a substantial H/He atmosphere of $2.1^{+0.8}_{-0.3}$ by mass, and joins a growing population of low-mass, low-density planets.Comment: 21 pages, 10 figures, 5 tables, accepted into Ap

Australia and New Zealand renal gene panel testing in routine clinical practice of 542 families

Genetic testing in nephrology clinical practice has moved rapidly from a rare specialized test to routine practice both in pediatric and adult nephrology. However, clear information pertaining to the likely outcome of testing is still missing. Here we describe the experience of the accredited Australia and New Zealand Renal Gene Panels clinical service, reporting on sequencing for 552 individuals from 542 families with suspected kidney disease in Australia and New Zealand. An increasing number of referrals have been processed since service inception with an overall diagnostic rate of 35%. The likelihood of identifying a causative variant varies according to both age at referral and gene panel. Although results from high throughput genetic testing have been primarily for diagnostic purposes, they will increasingly play an important role in directing treatment, genetic counseling, and family planning

Development of a treatment selection algorithm for SGLT2 and DPP-4 inhibitor therapies in people with type 2 diabetes:a retrospective cohort study

Background: Current treatment guidelines do not provide recommendations to support the selection of treatment for most people with type 2 diabetes. We aimed to develop and validate an algorithm to allow selection of optimal treatment based on glycaemic response, weight change, and tolerability outcomes when choosing between SGLT2 inhibitor or DPP-4 inhibitor therapies. Methods: In this retrospective cohort study, we identified patients initiating SGLT2 and DPP-4 inhibitor therapies after Jan 1, 2013, from the UK Clinical Practice Research Datalink (CPRD). We excluded those who received SGLT2 or DPP-4 inhibitors as first-line treatment or insulin at the same time, had estimated glomerular filtration rate (eGFR) of less than 45 mL/min per 1·73 m2, or did not have a valid baseline glycated haemoglobin (HbA1c) measure (<53 or ≥120 mmol/mol). The primary efficacy outcome was the HbA1c value reached 6 months after drug initiation, adjusted for baseline HbA1c. Clinical features associated with differential HbA1c outcome on the two therapies were identified in CPRD (n=26 877), and replicated in reanalysis of 14 clinical trials (n=10 414). An algorithm to predict individual-level differential HbA1c outcome on the two therapies was developed in CPRD (derivation; n=14 069) and validated in head-to-head trials (n=2499) and CPRD (independent validation; n=9376). In CPRD, we further explored heterogeneity in 6-month weight change and treatment discontinuation. Findings: Among 10 253 patients initiating SGLT2 inhibitors and 16 624 patients initiating DPP-4 inhibitors in CPRD, baseline HbA1c, age, BMI, eGFR, and alanine aminotransferase were associated with differential HbA1c outcome with SGLT2 inhibitor and DPP-4 inhibitor therapies. The median age of participants was 62·0 years (IQR 55·0–70·0). 10 016 (37·3%) were women and 16 861 (62·7%) were men. An algorithm based on these five features identified a subgroup, representing around four in ten CPRD patients, with a 5 mmol/mol or greater observed benefit with SGLT2 inhibitors in all validation cohorts (CPRD 8·8 mmol/mol [95% CI 7·8–9·8]; CANTATA-D and CANTATA-D2 trials 5·8 mmol/mol [3·9–7·7]; BI1245.20 trial 6·6 mmol/mol [2·2–11·0]). In CPRD, predicted differential HbA1c response with SGLT2 inhibitor and DPP-4 inhibitor therapies was not associated with weight change. Overall treatment discontinuation within 6 months was similar in patients predicted to have an HbA1c benefit with SGLT2 inhibitors over DPP-4 inhibitors (median 15·2% [13·2–20·3] vs 14·4% [12·9–16·7]). A smaller subgroup predicted to have greater HbA1c reduction with DPP-4 inhibitors were twice as likely to discontinue SGLT2 inhibitors than DPP-4 inhibitors (median 26·8% [23·4–31·0] vs 14·8% [12·9–16·8]). Interpretation: A validated treatment selection algorithm for SGLT2 inhibitor and DPP-4 inhibitor therapies can support decisions on optimal treatment for people with type 2 diabetes. Funding: BHF-Turing Cardiovascular Data Science Award and the UK Medical Research Council

Rethinking the patient: using Burden of Treatment Theory to understand the changing dynamics of illness

<b>Background</b> In this article we outline Burden of Treatment Theory, a new model of the relationship between sick people, their social networks, and healthcare services. Health services face the challenge of growing populations with long-term and life-limiting conditions, they have responded to this by delegating to sick people and their networks routine work aimed at managing symptoms, and at retarding - and sometimes preventing - disease progression. This is the new proactive work of patient-hood for which patients are increasingly accountable: founded on ideas about self-care, self-empowerment, and self-actualization, and on new technologies and treatment modalities which can be shifted from the clinic into the community. These place new demands on sick people, which they may experience as burdens of treatment.<p></p> <b>Discussion</b> As the burdens accumulate some patients are overwhelmed, and the consequences are likely to be poor healthcare outcomes for individual patients, increasing strain on caregivers, and rising demand and costs of healthcare services. In the face of these challenges we need to better understand the resources that patients draw upon as they respond to the demands of both burdens of illness and burdens of treatment, and the ways that resources interact with healthcare utilization.<p></p> <b>Summary</b> Burden of Treatment Theory is oriented to understanding how capacity for action interacts with the work that stems from healthcare. Burden of Treatment Theory is a structural model that focuses on the work that patients and their networks do. It thus helps us understand variations in healthcare utilization and adherence in different healthcare settings and clinical contexts

Natural Inflation: Particle Physics Models, Power Law Spectra for Large Scale Structure, and Constraints from COBE

A pseudo-Nambu-Goldstone boson, with a potential of the form $V(\phi) = \Lambda^4[1 \pm \cos(\phi/f)], naturally gives rise to inflation if$f \sim M_{Pl}$and$\Lambda \sim M_{GUT}$. We show how this can arise in technicolor-like and superstring models, and work out an explicit string example in the context of multiple gaugino condensation models. We study the cosmology of this model in detail, and find that sufficient reheating to ensure that baryogenesis can take place requires$f > 0.3 M_{Pl}$. The primordial density fluctuation spectrum generated is a non-scale-invariant power law,$P(k) \propto k^{n_s}$, with$n_s \simeq 1 - (M^2_{Pl}/8\pi f^2)$, leading to more power on large length scales than the$n_s = 1$Harrison-Zeldovich spectrum. The standard CDM model with$0 \la n_s \la 0.6-0.7$could in principle explain the large-scale clustering observed in the APM and IRAS galaxy surveys as well as large-scale flows, but the COBE microwave anisotropy implies such low amplitudes (or high bias factors,$b>2$) for these CDM models that galaxy formation occurs too late to be viable; combining COBE with sufficiently early galaxy formation or the large-scale flows leads to$n_s >0.6$, or$f > 0.3 M_{Pl}$as well. For extended and power law inflation models, this constraint is even tighter,$n_s > 0.7$; combined with other bounds on large bubbles in extended inflation, this leaves little room for most extended models.Comment: 42 pages, (12 figures not included but available from the authors

A randomised controlled trial to compare opt-in and opt-out parental consent for childhood vaccine safety surveillance using data linkage: study protocol

Extent: 10p.Background: The Vaccine Assessment using Linked Data (VALiD) trial compared opt-in and opt-out parental consent for a population-based childhood vaccine safety surveillance program using data linkage. A subsequent telephone interview of all households enrolled in the trial elicited parental intent regarding the return or non-return of reply forms for opt-in and opt-out consent. This paper describes the rationale for the trial and provides an overview of the design and methods. Methods/Design: Single-centre, single-blind, randomised controlled trial (RCT) stratified by firstborn status. Mothers who gave birth at one tertiary South Australian hospital were randomised at six weeks post-partum to receive an opt-in or opt-out reply form, along with information explaining data linkage. The primary outcome at 10 weeks post-partum was parental participation in each arm, as indicated by the respective return or non-return of a reply form (or via telephone or email response). A subsequent telephone interview at 10 weeks post-partum elicited parental intent regarding the return or non-return of the reply form, and attitudes and knowledge about data linkage, vaccine safety, consent preferences and vaccination practices. Enrolment began in July 2009 and 1,129 households were recruited in a three-month period. Analysis has not yet been undertaken. The participation rate and selection bias for each method of consent will be compared when the data are analysed. Discussion: The VALiD RCT represents the first trial of opt-in versus opt-out consent for a data linkage study that assesses consent preferences and intent compared with actual opting in or opting out behaviour, and socioeconomic factors. The limitations to generalisability are discussed.Jesia G Berry, Philip Ryan, Annette J Braunack-Mayer, Katherine M Duszynski, Vicki Xafis, Michael S Gold, the Vaccine Assessment Using Linked Data (VALiD) Working Grou

The Astropy Problem

The Astropy Project (http://astropy.org) is, in its own words, "a community effort to develop a single core package for Astronomy in Python and foster interoperability between Python astronomy packages." For five years this project has been managed, written, and operated as a grassroots, self-organized, almost entirely volunteer effort while the software is used by the majority of the astronomical community. Despite this, the project has always been and remains to this day effectively unfunded. Further, contributors receive little or no formal recognition for creating and supporting what is now critical software. This paper explores the problem in detail, outlines possible solutions to correct this, and presents a few suggestions on how to address the sustainability of general purpose astronomical software

Whole-body microbiota of newborn calves and their response to prenatal vitamin and mineral supplementation

Early life microbial colonization and factors affecting colonization patterns are gaining interest due to recent developments suggesting that early life microbiome may play a role in Developmental Origins of Health and Disease. In cattle, limited information exists on the early microbial colonization of anatomical sites involved in bovine health beyond the gastrointestinal tract. Here, we investigated 1) the initial microbial colonization of seven different anatomical locations in newborn calves and 2) whether these early life microbial communities and 3) serum cytokine profiles are influenced by prenatal vitamin and mineral (VTM) supplementation. Samples were collected from the hoof, liver, lung, nasal cavity, eye, rumen (tissue and fluid), and vagina of beef calves that were born from dams that either received or did not receive VTM supplementation throughout gestation (n = 7/group). Calves were separated from dams immediately after birth and fed commercial colostrum and milk replacer until euthanasia at 30 h post-initial colostrum feeding. The microbiota of all samples was assessed using 16S rRNA gene sequencing and qPCR. Calf serum was subjected to multiplex quantification of 15 bovine cytokines and chemokines. Our results indicated that the hoof, eye, liver, lung, nasal cavity, and vagina of newborn calves were colonized by site-specific microbiota, whose community structure differed from the ruminal-associated communities (0.64 ≥ R2 ≥ 0.12, p ≤ 0.003). The ruminal fluid microbial community was the only one that differed by treatment (p < 0.01). However, differences (p < 0.05) by treatment were detected in microbial richness (vagina); diversity (ruminal tissue, fluid, and eye); composition at the phylum and genus level (ruminal tissue, fluid, and vagina); and in total bacterial abundance (eye and vagina). From serum cytokines evaluated, concentration of chemokine IP-10 was greater (p = 0.02) in VTM calves compared to control calves. Overall, our results suggest that upon birth, the whole-body of newborn calves are colonized by relatively rich, diverse, and site-specific bacterial communities. Noticeable differences were observed in ruminal, vaginal, and ocular microbiota of newborn calves in response to prenatal VTM supplementation. These findings can derive future hypotheses regarding the initial microbial colonization of different body sites, and on maternal micronutrient consumption as a factor that may influence early life microbial colonization