The Roasting Marshmallows Program with IGRINS on Gemini South I: Composition and Climate of the Ultra Hot Jupiter WASP-18 b

We present high-resolution dayside thermal emission observations of the exoplanet WASP-18b using IGRINS on Gemini South. We remove stellar and telluric signatures using standard algorithms, and we extract the planet signal via cross correlation with model spectra. We detect the atmosphere of WASP-18b at a signal-to-noise ratio (SNR) of 5.9 using a full chemistry model, measure H2O (SNR=3.3), CO (SNR=4.0), and OH (SNR=4.8) individually, and confirm previous claims of a thermal inversion layer. The three species are confidently detected (>4$\sigma$) with a Bayesian inference framework, which we also use to retrieve abundance, temperature, and velocity information. For this ultra-hot Jupiter (UHJ), thermal dissociation processes likely play an important role. Retrieving abundances constant with altitude and allowing the temperature-pressure profile to freely adjust results in a moderately super-stellar carbon to oxygen ratio (C/O=0.75^{+0.14}_{-0.17}) and metallicity ([M/H]=1.03^{+0.65}_{-1.01}). Accounting for undetectable oxygen produced by thermal dissociation leads to C/O=0.45^{+0.08}_{-0.10} and [M/H]=1.17^{+0.66}_{-1.01}. A retrieval that assumes radiative-convective-thermochemical-equilibrium and naturally accounts for thermal dissociation constrains C/O<0.34 (2$\sigma$) and [M/H]=0.48^{+0.33}_{-0.29}, in line with the chemistry of the parent star. Looking at the velocity information, we see a tantalising signature of different Doppler shifts at the level of a few km/s for different molecules, which might probe dynamics as a function of altitude and location on the planet disk. Our results demonstrate that ground-based, high-resolution spectroscopy at infrared wavelengths can provide meaningful constraints on the compositions and climate of highly irradiated planets. This work also elucidates potential pitfalls with commonly employed retrieval assumptions when applied to UHJ spectra.Comment: 27 pages, 18 figures, submitted to AAS Journals. Community feedback welcom

Mental fortitude training: An evidence-based approach to developing psychological resilience for sustained success

Drawing on the body of knowledge in this area, this article presents an evidence-based approach to developing psychological resilience for sustained success. To this end, the narrative is divided into three main sections. The first section describes the construct of psychological resilience and explains what it is. The second section outlines and discusses a mental fortitude training™ program for aspiring performers. The third section provides recommendations for practitioners implementing this program. It is hoped that this article will facilitate a holistic and systematic approach to developing resilience for sustained success

Riding the Wave: Reconciling the Roles of Disease and Climate Change in Amphibian Declines

We review the evidence for the role of climate change in triggering disease outbreaks of chytridiomycosis, an emerging infectious disease of amphibians. Both climatic anomalies and disease-related extirpations are recent phenomena, and effects of both are especially noticeable at high elevations in tropical areas, making it difficult to determine whether they are operating separately or synergistically. We compiled reports of amphibian declines from Lower Central America and Andean South America to create maps and statistical models to test our hypothesis of spatiotemporal spread of the pathogen Batrachochytrium dendrobatidis (Bd), and to update the elevational patterns of decline in frogs belonging to the genus Atelopus. We evaluated claims of climate change influencing the spread of Bd by including error into estimates of the relationship between air temperature and last year observed. Available data support the hypothesis of multiple introductions of this invasive pathogen into South America and subsequent spread along the primary Andean cordilleras. Additional analyses found no evidence to support the hypothesis that climate change has been driving outbreaks of amphibian chytridiomycosis, as has been posited in the climate-linked epidemic hypothesis. Future studies should increase retrospective surveys of museum specimens from throughout the Andes and should study the landscape genetics of Bd to map fine-scale patterns of geographic spread to identify transmission routes and processes

Riding the Wave: Reconciling the Roles of Disease and Climate Change in Amphibian Declines

We review the evidence for the role of climate change in triggering disease outbreaks of chytridiomycosis, an emerging infectious disease of amphibians. Both climatic anomalies and disease-related extirpations are recent phenomena, and effects of both are especially noticeable at high elevations in tropical areas, making it difficult to determine whether they are operating separately or synergistically. We compiled reports of amphibian declines from Lower Central America and Andean South America to create maps and statistical models to test our hypothesis of spatiotemporal spread of the pathogen Batrachochytrium dendrobatidis (Bd), and to update the elevational patterns of decline in frogs belonging to the genus Atelopus. We evaluated claims of climate change influencing the spread of Bd by including error into estimates of the relationship between air temperature and last year observed. Available data support the hypothesis of multiple introductions of this invasive pathogen into South America and subsequent spread along the primary Andean cordilleras. Additional analyses found no evidence to support the hypothesis that climate change has been driving outbreaks of amphibian chytridiomycosis, as has been posited in the climate-linked epidemic hypothesis. Future studies should increase retrospective surveys of museum specimens from throughout the Andes and should study the landscape genetics of Bd to map fine-scale patterns of geographic spread to identify transmission routes and processes

Enabling the Development and Deployment of Next Generation Point-of-Care Diagnostics

<p>Enabling the Development and Deployment of Next Generation Point-of-Care Diagnostics</p

The Macroecology of Sustainability

Global consumption rates of vital resources suggest that we have surpassed the capacity of the Earth to sustain current levels, much less future trajectories of growth in human population and economy

Daratumumab plus lenalidomide and dexamethasone for untreated myeloma

This is an accepted manuscript of an article published by Massachusetts Medical Society in New England Journal of Medicine on 30/05/2019, available online: https://doi.org/10.1056/NEJMoa1817249 The accepted version of the publication may differ from the final published version.Copyright © 2019 Massachusetts Medical Society. Lenalidomide plus dexamethasone is a standard treatment for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem-cell transplantation. We sought to determine whether the addition of daratumumab would significantly reduce the risk of disease progression or death in this population. METHODS We randomly assigned 737 patients with newly diagnosed multiple myeloma who were ineligible for autologous stem-cell transplantation to receive daratumumab plus lenalidomide and dexamethasone (daratumumab group) or lenalidomide and dexamethasone alone (control group). Treatment was to continue until the occurrence of disease progression or unacceptable side effects. The primary end point was progression-free survival. RESULTS At a median follow-up of 28.0 months, disease progression or death had occurred in 240 patients (97 of 368 patients [26.4%] in the daratumumab group and 143 of 369 patients [38.8%] in the control group). The estimated percentage of patients who were alive without disease progression at 30 months was 70.6% (95% confidence interval [CI], 65.0 to 75.4) in the daratumumab group and 55.6% (95% CI, 49.5 to 61.3) in the control group (hazard ratio for disease progression or death, 0.56; 95% CI, 0.43 to 0.73; P<0.001). The percentage of patients with a complete response or better was 47.6% in the daratumumab group and 24.9% in the control group (P<0.001). A total of 24.2% of the patients in the daratumumab group, as compared with 7.3% of the patients in the control group, had results below the threshold for minimal residual disease (1 tumor cell per 105 white cells) (P<0.001). The most common adverse events of grade 3 or 4 were neutropenia (50.0% in the daratumumab group vs. 35.3% in the control group), anemia (11.8% vs. 19.7%), lymphopenia (15.1% vs. 10.7%), and pneumonia (13.7% vs. 7.9%).Published versio

Plant-symbiotic fungi as chemical engineers: multi-genome analysis of the Clavicipitaceae reveals dynamics of alkaloid Loci

The fungal family Clavicipitaceae includes plant symbionts and parasites that produce several psychoactive and bioprotective alkaloids. The family includes grass symbionts in the epichloae clade (Epichloë and Neotyphodium species), which are extraordinarily diverse both in their host interactions and in their alkaloid profiles. Epichloae produce alkaloids of four distinct classes, all of which deter insects, and some—including the infamous ergot alkaloids—have potent effects on mammals. The exceptional chemotypic diversity of the epichloae may relate to their broad range of host interactions, whereby some are pathogenic and contagious, others are mutualistic and vertically transmitted (seed-borne), and still others vary in pathogenic or mutualistic behavior. We profiled the alkaloids and sequenced the genomes of 10 epichloae, three ergot fungi (Claviceps species), a morning-glory symbiont (Periglandula ipomoeae), and a bamboo pathogen (Aciculosporium take), and compared the gene clusters for four classes of alkaloids. Results indicated a strong tendency for alkaloid loci to have conserved cores that specify the skeleton structures and peripheral genes that determine chemical variations that are known to affect their pharmacological specificities. Generally, gene locations in cluster peripheries positioned them near to transposon-derived, AT-rich repeat blocks, which were probably involved in gene losses, duplications, and neofunctionalizations. The alkaloid loci in the epichloae had unusual structures riddled with large, complex, and dynamic repeat blocks. This feature was not reflective of overall differences in repeat contents in the genomes, nor was it characteristic of most other specialized metabolism loci. The organization and dynamics of alkaloid loci and abundant repeat blocks in the epichloae suggested that these fungi are under selection for alkaloid diversification. We suggest that such selection is related to the variable life histories of the epichloae, their protective roles as symbionts, and their associations with the highly speciose and ecologically diverse cool-season grasses

Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers

The risk of germline copy number variants (CNVs) in BRCA1 and BRCA2 pathogenic variant carriers in breast cancer is assessed, with CNVs overlapping SULT1A1 decreasing breast cancer risk in BRCA1 carriers.The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09-1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.Peer reviewe