Evidence for a circumplanetary disk around protoplanet PDS 70 b

We present the first observational evidence for a circumplanetary disk around the protoplanet PDS~70~b, based on a new spectrum in the $K$ band acquired with VLT/SINFONI. We tested three hypotheses to explain the spectrum: Atmospheric emission from the planet with either (1) a single value of extinction or (2) variable extinction, and (3) a combined atmospheric and circumplanetary disk model. Goodness-of-fit indicators favour the third option, suggesting circumplanetary material contributing excess thermal emission --- most prominent at $\lambda \gtrsim 2.3 \mu$m. Inferred accretion rates ($\sim 10^{-7.8}$--$10^{-7.3} M_J$ yr$^{-1}$) are compatible with observational constraints based on the H$\alpha$ and Br$\gamma$ lines. For the planet, we derive an effective temperature of 1500--1600 K, surface gravity $\log(g)\sim 4.0$, radius $\sim 1.6 R_J$, mass $\sim 10 M_J$, and possible thick clouds. Models with variable extinction lead to slightly worse fits. However, the amplitude ($\Delta A_V \gtrsim 3$mag) and timescale of variation ($\lesssim$~years) required for the extinction would also suggest circumplanetary material.Comment: 8 pages, 2 figures, 1 table. This is a pre-copyedited, author-produced PDF of an article accepted for publication in ApJL on 2019 May 1

A Direct Imaging Survey of Spitzer detected debris disks: Occurrence of giant planets in dusty systems

We describe a joint high contrast imaging survey for planets at Keck and VLT of the last large sample of debris disks identified by the Spitzer Space Telescope. No new substellar companions were discovered in our survey of 30 Spitzer-selected targets. We combine our observations with data from four published surveys to place constraints on the frequency of planets around 130 debris disk single stars, the largest sample to date. For a control sample, we assembled contrast curves from several published surveys targeting 277 stars which do not show infrared excesses. We assumed a double power law distribution in mass and semi-major axis of the form f(m,a) = $Cm^{\alpha}a^{\beta}$, where we adopted power law values and logarithmically flat values for the mass and semi-major axis of planets. We find that the frequency of giant planets with masses 5-20 $M_{\rm Jup}$ and separations 10-1000 AU around stars with debris disks is 6.27% (68% confidence interval 3.68 - 9.76%), compared to 0.73% (68% confidence interval 0.20 - 1.80%) for the control sample of stars without disks. These distributions differ at the 88% confidence level, tentatively suggesting distinctness of these samples.Comment: Accepted to A

Hardware Sequencing of Inflatable Nonlinear Actuators for Autonomous Soft Robots

Soft robots are an interesting alternative for classic rigid robots in appli-cations requiring interaction with organisms or delicate objects. Elastic inflatable actuators are one of the preferred actuation mechanisms for soft robots since they are intrinsically safe and soft. However, these pneumatic actuators each require a dedicated pressure supply and valve to drive and control their actuation sequence. Because of the relatively large size of pres-sure supplies and valves compared to electrical leads and electronic control-lers, tethering pneumatic soft robots with multiple degrees of freedom is bulky and unpractical. Here, a new approach is described to embed hardware intelligence in soft robots where multiple actuators are attached to the same pressure supply, and their actuation sequence is programmed by the inter-action between nonlinear actuators and passive flow restrictions. How to model this hardware sequencing is discussed, and it is demonstrated on an 8-degree-of-freedom walking robot where each limb comprises two actua-tors with a sequence embedded in their hardware. The robot is able to carry pay loads of 800 g in addition to its own weight and is able to walk at travel speeds of 3 body lengths per minute, without the need for complex on-board valves or bulky tethers.ERC starting gran

Identifying Health Economic Considerations to Include in the Research Protocol of a Randomized Controlled Trial (the REDUCE-RISK Trial): Systematic Literature Review and Assessment.

BACKGROUND: The REDUCE-RISK trial was set up to compare the effectiveness of weekly subcutaneously administered methotrexate with daily oral azathioprine or 6-mercaptopurine in low-risk Crohn disease (CD) or subcutaneously administered adalimumab (ADA) in high-risk CD in a pediatric population (age 6-17 years). OBJECTIVE: The aim of this study is to perform a systematic review to provide input into the research protocol to gather the necessary information to improve the performance of an evidence-based economic evaluation when the trial is finished. METHODS: The Centre for Reviews and Dissemination (CRD) Health Technology Assessment (HTA) database, websites of HTA institutes, CRD's National Health Service Economic Evaluation Database, MEDLINE (OVID), and Embase databases were consulted to retrieve (reviews of) relevant economic evaluations. Studies were eligible if they included a pediatric or adult population with inflammatory bowel diseases (CD and ulcerative colitis [UC]) treated with ADA (Humira). There were no restrictions on the comparator. Only economic evaluations expressing outcomes in life years gained or quality-adjusted life years gained were selected. RESULTS: A total of 12 primary studies were identified. None of these studies included a pediatric population because of a lack of supporting trials. The economic evaluations identified in our systematic review indicate that ADA is an appropriate intervention for inclusion in such a trial. From a health economic point of view, it is important to make an incremental analysis comparing such an intervention with standard care and not immediately versus another (expensive) biological treatment. Information on the impact of children's school attendance and parents' productivity is currently lacking in economic evaluations, and none of the underlying trials measured quality of life (QoL) using a generic utility instrument. CONCLUSIONS: The review of the economic literature on ADA for the treatment of patients with CD supports the performance of a trial with biologicals in pediatric patients, including making a distinction according to disease severity. Conducting an economic literature review enabled us to decide which variables should be added to the research protocol from an economic point of view. Measurements for children's and parents' QoL (EuroQol 5-Dimension questionnaires), children's school attendance, and parents' productivity (WPAI-CD-CG questionnaire) were added to the research protocol. This will provide support for the calculation of the cost-effectiveness of the interventions evaluated in the REDUCE-RISK trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT02852694; https://clinicaltrials.gov/ct2/show/NCT02852694

Parental age effects on neonatal white matter development.

OBJECTIVE: Advanced paternal age is associated with poor offspring developmental outcome. Though an increase in paternal age-related germline mutations may affect offspring white matter development, outcome differences could also be due to psychosocial factors. Here we investigate possible cerebral changes prior to strong environmental influences using brain MRI in a cohort of healthy term-born neonates. METHODS: We used structural and diffusion MRI images acquired soon after birth from a cohort (n = 275) of healthy term-born neonates. Images were analysed using a customised tract based spatial statistics (TBSS) processing pipeline. Neurodevelopmental assessment using the Bayley-III scales was offered to all participants at age 18 months. For statistical analysis neonates were compared in two groups, representing the upper quartile (paternal age ≥38 years) and lower three quartiles. The same method was used to assess associations with maternal age. RESULTS: In infants with older fathers (≥38 years), fractional anisotropy, a marker of white matter organisation, was significantly reduced in three early maturing anatomical locations (the corticospinal tract, the corpus callosum, and the optic radiation). Fractional anisotropy in these locations correlated positively with Bayley-III cognitive composite score at 18 months in the advanced paternal age group. A small but significant reduction in total brain volume was also observed in in the infants of older fathers. No significant associations were found between advanced maternal age and neonatal imaging. CONCLUSIONS: The epidemiological association between advanced paternal age and offspring outcome is extremely robust. We have for the first time demonstrated a neuroimaging phenotype of advanced paternal age before sustained parental interaction that correlates with later outcome

The Gene expression Grade Index: a potential predictor of relapse for endocrine-treated breast cancer patients in the BIG 1–98 trial

<p>Abstract</p> <p>Background</p> <p>We have previously shown that the Gene expression Grade Index (GGI) was able to identify two subtypes of estrogen receptor (ER)-positive tumors that were associated with statistically distinct clinical outcomes in both untreated and tamoxifen-treated patients. Here, we aim to investigate the ability of the GGI to predict relapses in postmenopausal women who were treated with tamoxifen (T) or letrozole (L) within the BIG 1–98 trial.</p> <p>Methods</p> <p>We generated gene expression profiles (Affymetrix) and computed the GGI for a matched, case-control sample of patients enrolled in the BIG 1–98 trial from the two hospitals where frozen samples were available. All relapses (cases) were identified from patients randomized to receive monotherapy or from the switching treatment arms for whom relapse occurred before the switch. Each case was randomly matched with four controls based upon nodal status and treatment (T or L). The prognostic value of GGI was assessed as a continuous predictor and divided at the median. Predictive accuracy of GGI was estimated using time-dependent area under the curve (AUC) of the ROC curves.</p> <p>Results</p> <p>Frozen samples were analyzable for 48 patients (10 cases and 38 controls). Seven of the 10 cases had been assigned to receive L. Cases and controls were comparable with respect to menopausal and nodal status, local and chemotherapy, and HER2 positivity. Cases were slightly older than controls and had a larger proportion of large, poorly differentiated ER+/PgR- tumors. The GGI was significantly and linearly related to risk of relapse: each 10-unit increase in GGI resulted in an increase of approximately 11% in the hazard rate (p = 0.02). Within the subgroups of patients with node-positive disease or who were treated with L, the hazard of relapse was significantly greater for patients with GGI at or above the median. AUC reached a maximum of 78% at 27 months.</p> <p>Conclusion</p> <p>This analysis supports the GGI as a good predictor of relapse for ER-positive patients, even among patients who receive L. Validation of these results, in a larger series from BIG 1–98, is planned using the simplified GGI represented by a smaller set of genes and tested by qRT-PCR on paraffin-embedded tissues.</p