ATOCA: an algorithm to treat order contamination. Application to the NIRISS SOSS mode

After a successful launch, the James Webb Space Telescope is preparing to undertake one of its principal missions, the characterization of the atmospheres of exoplanets. The Single Object Slitless Spectroscopy (SOSS) mode of the Near Infrared Imager and Slitless Spectrograph (NIRISS) is the only observing mode that has been specifically designed for this objective. It features a wide simultaneous spectral range (0.6--2.8\,\micron) through two spectral diffraction orders. However, due to mechanical constraints, these two orders overlap slightly over a short range, potentially introducing a ``contamination'' signal in the extracted spectrum. We show that for a typical box extraction, this contaminating signal amounts to 1\% or less over the 1.6--2.8\,\micron\ range (order 1), and up to 1\% over the 0.85--0.95\,\micron\ range (order 2). For observations of exoplanet atmospheres (transits, eclipses or phase curves) where only temporal variations in flux matter, the contamination signal typically biases the results by order of 1\% of the planetary atmosphere spectral features strength. To address this problem, we developed the Algorithm to Treat Order ContAmination (ATOCA). By constructing a linear model of each pixel on the detector, treating the underlying incident spectrum as a free variable, ATOCA is able to perform a simultaneous extraction of both orders. We show that, given appropriate estimates of the spatial trace profiles, the throughputs, the wavelength solutions, as well as the spectral resolution kernels for each order, it is possible to obtain an extracted spectrum accurate to within 10\,ppm over the full spectral range.Comment: Submitted to PASP. 22 pages, 12 figure

A crossover randomised controlled trial of oral mandibular advancement devices for obstructive sleep apnoea-hypopnoea (TOMADO)

Rationale Mandibular advancement devices (MADs) are used to treat obstructive sleep apnoea-hypopnoea syndrome (OSAHS) but evidence is lacking regarding their clinical and cost-effectiveness in less severe disease. Objectives To compare clinical- and cost-effectiveness of a range of MADs against no treatment in mild to moderate OSAHS. Measurements and methods This open-label, randomised, controlled, crossover trial was undertaken at a UK sleep centre. Adults with Apnoea-Hypopnoea Index (AHI) 5–<30/h and Epworth Sleepiness Scale (ESS) score ≥9 underwent 6 weeks of treatment with three nonadjustable MADs: self-moulded (SleepPro 1; SP1); semi-bespoke (SleepPro 2; SP2); fully-bespoke MAD (bMAD); and 4 weeks no treatment. Primary outcome was AHI scored by a polysomnographer blinded to treatment. Secondary outcomes included ESS, quality of life, resource use and cost. Main results 90 patients were randomised and 83 were analysed. All devices reduced AHI compared with no treatment by 26% (95% CI 11% to 38%, p=0.001) for SP1, 33% (95% CI 24% to 41%) for SP2 and 36% (95% CI 24% to 45%, p<0.001) for bMAD. ESS was 1.51 (95% CI 0.73 to 2.29, p<0.001, SP1) to 2.37 (95% CI 1.53 to 3.22, p<0.001, bMAD) lower than no treatment (p<0.001 for all). Compliance was lower for SP1, which was the least preferred treatment at trial exit. All devices were cost-effective compared with no treatment at a £20 000/quality-adjusted life year (QALY) threshold. SP2 was the most cost-effective up to £39 800/QALY. Conclusions Non-adjustable MADs achieve clinically important improvements in mild to moderate OSAHS and are cost-effective

Near-Infrared Transmission Spectroscopy of HAT-P-18 \,b with NIRISS: Disentangling Planetary and Stellar Features in the Era of JWST

The JWST Early Release Observations (ERO) included a NIRISS/SOSS (0.6-2.8$\,\mu$m) transit of the $\sim\,$850$\,$K Saturn-mass exoplanet HAT-P-18$\,$b. Initial analysis of these data reported detections of water, escaping helium, and haze. However, active K dwarfs like HAT-P-18 possess surface heterogeneities $-$ starspots and faculae $-$ that can complicate the interpretation of transmission spectra, and indeed, a spot-crossing event is present in HAT-P-18$\,$b's NIRISS/SOSS light curves. Here, we present an extensive reanalysis and interpretation of the JWST ERO transmission spectrum of HAT-P-18$\,$b, as well as HST/WFC3 and $\textit{Spitzer}$/IRAC transit observations. We detect H$_2$O (12.5$\,\sigma$), CO$_2$ (7.3$\,\sigma$), a cloud deck (7.4$\,\sigma$), and unocculted starspots (5.8$\,\sigma$), alongside hints of Na (2.7$\,\sigma$). We do not detect the previously reported CH$_4$ ($\log$ CH$_4$ $<$ -6 to 2$\,\sigma$). We obtain excellent agreement between three independent retrieval codes, which find a sub-solar H$_2$O abundance ($\log$ H$_2$O $\approx -4.4 \pm 0.3$). However, the inferred CO$_2$ abundance ($\log$ CO$_2$ $\approx -4.8 \pm 0.4$) is significantly super-solar and requires further investigation into its origin. We also introduce new stellar heterogeneity considerations by fitting for the active regions' surface gravities $-$ a proxy for the effects of magnetic pressure. Finally, we compare our JWST inferences to those from HST/WFC3 and $\textit{Spitzer}$/IRAC. Our results highlight the exceptional promise of simultaneous planetary atmosphere and stellar heterogeneity constraints in the era of JWST and demonstrate that JWST transmission spectra may warrant more complex treatments of the transit light source effect

Weight loss, insulin resistance, and study design confound results in a meta-analysis of animal models of fatty liver

The classical drug development pipeline necessitates studies using animal models of human disease to gauge future efficacy in humans, however there is a low conversion rate from success in animals to humans. Non-alcoholic fatty liver disease (NAFLD) is a complex chronic disease without any established therapies and a major field of animal research. We performed a meta-analysis with meta-regression of 603 interventional rodent studies (10,364 animals) in NAFLD to assess which variables influenced treatment response. Weight loss and alleviation of insulin resistance were consistently associated with improvement in NAFLD. Multiple drug classes that do not affect weight in humans caused weight loss in animals. Other study design variables, such as age of animals and dietary composition, influenced the magnitude of treatment effect. Publication bias may have increased effect estimates by 37-79%. These findings help to explain the challenge of reproducibility and translation within the field of metabolism

Characterizing the Near-infrared Spectra of Flares from TRAPPIST-1 During JWST Transit Spectroscopy Observations

We present the first analysis of JWST near-infrared spectroscopy of stellar flares from TRAPPIST-1 during transits of rocky exoplanets. Four flares were observed from 0.6--2.8 $\mu$m with NIRISS and 0.6--3.5 $\mu$m with NIRSpec during transits of TRAPPIST-1b, f, and g. We discover P$\alpha$ and Br$\beta$ line emission and characterize flare continuum at wavelengths from 1--3.5 $\mu$m for the first time. Observed lines include H$\alpha$, P$\alpha$-P$\epsilon$, Br$\beta$, He I $\lambda$0.7062$\mu$m, two Ca II infrared triplet (IRT) lines, and the He I IRT. We observe a reversed Paschen decrement from P$\alpha$-P$\gamma$ alongside changes in the light curve shapes of these lines. The continuum of all four flares is well-described by blackbody emission with an effective temperature below 5300 K, lower than temperatures typically observed at optical wavelengths. The 0.6--1 $\mu$m spectra were convolved with the TESS response, enabling us to measure the flare rate of TRAPPIST-1 in the TESS bandpass. We find flares of 10$^{30}$ erg large enough to impact transit spectra occur at a rate of 3.6$\substack{+2.1 \\ -1.3}$ flare d$^{-1}$, $\sim$10$\times$ higher than previous predictions from K2. We measure the amount of flare contamination at 2 $\mu$m for the TRAPPIST-1b and f transits to be 500$\pm$450 and 2100$\pm$400 ppm, respectively. We find up to 80% of flare contamination can be removed, with mitigation most effective from 1.0--2.4 $\mu$m. These results suggest transits affected by flares may still be useful for atmospheric characterization efforts.Comment: 29 pages, 17 figures, 3 tables, accepted to The Astrophysical Journa

REEP5 depletion causes sarco-endoplasmic reticulum vacuolization and cardiac functional defects

The sarco-endoplasmic reticulum (SR/ER) plays an important role in the development and progression of many heart diseases. However, many aspects of its structural organization remain largely unknown, particularly in cells with a highly differentiated SR/ER network. Here, we report a cardiac enriched, SR/ER membrane protein, REEP5 that is centrally involved in regulating SR/ER organization and cellular stress responses in cardiac myocytes. In vitro REEP5 depletion in mouse cardiac myocytes results in SR/ER membrane destabilization and luminal vacuolization along with decreased myocyte contractility and disrupted Ca2+ cycling. Further, in vivo CRISPR/Cas9-mediated REEP5 loss-of-function zebrafish mutants show sensitized cardiac dysfunction upon short-term verapamil treatment. Additionally, in vivo adeno-associated viral (AAV9)-induced REEP5 depletion in the mouse demonstrates cardiac dysfunction. These results demonstrate the critical role of REEP5 in SR/ER organization and function as well as normal heart function and development

A global scientific strategy to cure hepatitis B

Chronic hepatitis B virus (HBV) infection is a global public health challenge on the same scale as tuberculosis, HIV, and malaria. The International Coalition to Eliminate HBV (ICE-HBV) is a coalition of experts dedicated to accelerating the discovery of a cure for chronic hepatitis B. Following extensive consultation with more than 50 scientists from across the globe, as well as key stakeholders including people affected by HBV, we have identified gaps in our current knowledge and new strategies and tools that are required to achieve HBV cure. We believe that research must focus on the discovery of interventional strategies that will permanently reduce the number of productively infected cells or permanently silence the covalently closed circular DNA in those cells, and that will stimulate HBV-specific host immune responses which mimic spontaneous resolution of HBV infection. There is also a pressing need for the establishment of repositories of standardised HBV reagents and protocols that can be accessed by all HBV researchers throughout the world. The HBV cure research agenda outlined in this position paper will contribute markedly to the goal of eliminating HBV infection worldwide

High-spectral-resolution Observations of the Optical Filamentary Nebula Surrounding NGC 1275

We present new high-spectral-resolution observations (R = λ/Δλ = 7000) of the filamentary nebula surrounding NGC 1275, the central galaxy of the Perseus cluster. These observations have been obtained with SITELLE, an imaging Fourier transform spectrometer installed on the Canada–France–Hawai Telescope with a field of view of 11′×11′ , encapsulating the entire filamentary structure of ionized gas despite its large size of 80 kpc × 50 kpc. Here, we present renewed fluxes, velocities, and velocity dispersion maps that show in great detail the kinematics of the optical nebula at [S ii] λ6716, [S ii] λ6731, [N ii] λ6584, Hα (6563 Å), and [N ii] λ6548. These maps reveal the existence of a bright flattened disk-shaped structure in the core extending to r ∼10 kpc and dominated by a chaotic velocity field. This structure is located in the wake of X-ray cavities and characterized by a high mean velocity dispersion of 134 km s−1. The disk-shaped structure is surrounded by an extended array of filaments spread out to r ∼ 50 kpc that are 10 times fainter in flux, remarkably quiescent, and have a uniform mean velocity dispersion of 44 km s−1. This stability is puzzling given that the cluster core exhibits several energetic phenomena. Based on these results, we argue that there are two mechanisms that form multiphase gas in clusters of galaxies: a first triggered in the wake of X-ray cavities leading to more turbulent multiphase gas and a second, distinct mechanism, that is gentle and leads to large-scale multiphase gas spreading throughout the core

Open Problems in DAOs

Decentralized autonomous organizations (DAOs) are a new, rapidly-growing class of organizations governed by smart contracts. Here we describe how researchers can contribute to the emerging science of DAOs and other digitally-constituted organizations. From granular privacy primitives to mechanism designs to model laws, we identify high-impact problems in the DAO ecosystem where existing gaps might be tackled through a new data set or by applying tools and ideas from existing research fields such as political science, computer science, economics, law, and organizational science. Our recommendations encompass exciting research questions as well as promising business opportunities. We call on the wider research community to join the global effort to invent the next generation of organizations