Predicting Adverse Outcomes in End Stage Renal Disease: Machine Learning Applied to the United States Renal Data System

We examined machine learning methods to predict death within six months using data derived from the United States Renal Data System (USRDS). We specifically evaluated a generalized linear model, a support vector machine, a decision tree and a random forest evaluated within the context of K-10 fold validation using the CARET package available within the open source architecture R program. We compared these models with the feed forward neural network strategy that we previously reported on with this data set

Predicting Adverse Outcomes in End Stage Renal Disease: Machine Learning Applied to the United States Renal Data System

We examined machine learning methods to predict death within six months using data derived from the United States Renal Data System (USRDS). We specifically evaluated a generalized linear model, a support vector machine, a decision tree and a random forest evaluated within the context of K-10 fold validation using the CARET package available within the open source architecture R program. We compared these models with the feed forward neural network strategy that we previously reported on with this data set

Pooled analysis of iron-related genes in Parkinson's disease: Association with transferrin

Pathologic features of Parkinson's disease (PD) include death of dopaminergic neurons in the substantia nigra, presence of α-synuclein containing Lewy bodies, and iron accumulation in PD-related brain regions. The observed iron accumulation may be contributing to PD etiology but it also may be a byproduct of cell death or cellular dysfunction. To elucidate the possible role of iron accumulation in PD, we investigated genetic variation in 16 genes related to iron homeostasis in three case-control studies from the United States, Australia, and France. After screening 90 haplotype tagging single nucleotide polymorphisms (SNPs) within the genes of interest in the US study population, we investigated the five most promising gene regions in two additional independent case-control studies. For the pooled data set (1289 cases, 1391 controls) we observed a protective association (OR. = 0.83, 95% CI: 0.71-0.96) between PD and a haplotype composed of the A allele at rs1880669 and the T allele at rs1049296 in transferrin (TF; GeneID: 7018). Additionally, we observed a suggestive protective association (OR. = 0.87, 95% CI: 0.74-1.02) between PD and a haplotype composed of the G allele at rs10247962 and the A allele at rs4434553 in transferrin receptor 2 (TFR2; GeneID: 7036). We observed no associations in our pooled sample for haplotypes in SLC40A1, CYB561, or HFE. Taken together with previous findings in model systems, our results suggest that TF or a TF- TFR2 complex may have a role in the etiology of PD, possibly through iron misregulation or mitochondrial dysfunction within dopaminergic neurons

Awesome SOSS: Transmission Spectroscopy of WASP-96b with NIRISS/SOSS

The future is now - after its long-awaited launch in December 2021, JWST began science operations in July 2022 and is already revolutionizing exoplanet astronomy. The Early Release Observations (ERO) program was designed to provide the first images and spectra from JWST, covering a multitude of science cases and using multiple modes of each on-board instrument. Here, we present transmission spectroscopy observations of the hot-Saturn WASP-96b with the Single Object Slitless Spectroscopy (SOSS) mode of the Near Infrared Imager and Slitless Spectrograph, observed as part of the ERO program. As the SOSS mode presents some unique data reduction challenges, we provide an in-depth walk-through of the major steps necessary for the reduction of SOSS data: including background subtraction, correction of 1/f noise, and treatment of the trace order overlap. We furthermore offer potential routes to correct for field star contamination, which can occur due to the SOSS mode's slitless nature. By comparing our extracted transmission spectrum with grids of atmosphere models, we find an atmosphere metallicity between 1x and 5x solar, and a solar carbon-to-oxygen ratio. Moreover, our models indicate that no grey cloud deck is required to fit WASP-96b's transmission spectrum, but find evidence for a slope shortward of 0.9$\mu$m, which could either be caused by enhanced Rayleigh scattering or the red wing of a pressure-broadened Na feature. Our work demonstrates the unique capabilities of the SOSS mode for exoplanet transmission spectroscopy and presents a step-by-step reduction guide for this new and exciting instrument.Comment: MNRAS, in press. Updated to reflect published versio

Dimethyl Sulfoxide Induces Both Direct and Indirect Tau Hyperphosphorylation

Dimethyl sulfoxide (DMSO) is widely used as a solvent or vehicle for biological studies, and for treatment of specific disorders, including traumatic brain injury and several forms of amyloidosis. As Alzheimer’s disease (AD) brains are characterized by deposits of β-amyloid peptides, it has been suggested that DMSO could be used as a treatment for this devastating disease. AD brains are also characterized by aggregates of hyperphosphorylated tau protein, but the effect of DMSO on tau phosphorylation is unknown. We thus investigated the impact of DMSO on tau phosphorylation in vitro and in vivo. One hour following intraperitoneal administration of 1 or 2 ml/kg DMSO in mice, no change was observed in tau phosphorylation. However, at 4 ml/kg, tau was hyperphosphorylated at AT8 (Ser202/Thr205), PHF-1 (Ser396/Ser404) and AT180 (Thr231) epitopes. At this dose, we also noticed that the animals were hypothermic. When the mice were maintained normothermic, the effect of 4 ml/kg DMSO on tau hyperphosphorylation was prevented. On the other hand, in SH-SY5Y cells, 0.1% DMSO induced tau hyperphosphorylation at AT8 and AT180 phosphoepitopes in normothermic conditions. Globally, these findings demonstrate that DMSO can induce tau hyperphosphorylation indirectly via hypothermia in vivo, and directly in vitro. These data should caution researchers working with DMSO as it can induce artifactual results both in vivo and in vitro

Single blind randomized Phase III trial to investigate the benefit of a focal lesion ablative microboost in prostate cancer (FLAME-trial): study protocol for a randomized controlled trial

Background: The treatment results of external beam radiotherapy for intermediate and high risk prostate cancer patients are insufficient with five-year biochemical relapse rates of approximately 35%. Several randomized trials have shown that dose escalation to the entire prostate improves biochemical disease free survival. However, further dose escalation to the whole gland is limited due to an unacceptable high risk of acute and late toxicity. Moreover, local recurrences often originate at the location of the macroscopic tumor, so boosting the radiation dose at the macroscopic tumor within the prostate might increase local control. A reduction of distant metastases and improved survival can be expected by reducing local failure. The aim of this study is to investigate the benefit of an ablative microboost to the macroscopic tumor within the prostate in patients treated with external beam radiotherapy for prostate cancer.Methods/Design: The FLAME-trial (Focal Lesion Ablative Microboost in prostatE cancer) is a single blind randomized controlled phase III trial. We aim to include 566 patients (283 per treatment arm) with intermediate or high risk adenocarcinoma of the prostate who are scheduled for external beam radiotherapy using fiducial markers for position verification. With this number of patients, the expected increase in five-year freedom from biochemical failure rate of 10% can be detected with a power of 80%. Patients allocated to the standard arm receive a dose of 77 Gy in 35 fractions to the entire prostate and patients in the experimental arm receive 77 Gy to the entire prostate and an additional integrated microboost to the macroscopic tumor of 95 Gy in 35 fractions. The secondary outcome measures include treatment-related toxicity, quality of life and disease-specific survival. Furthermore, by localizing the recurrent tumors within the prostate during follow-up and correlating this with the delivered dose, we can obtain accurate dose-effect information for both the macroscopic tumor and subclinical disease in prostate cancer. The rationale, study design and the first 50 patients included are described.Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Early Release Science of the exoplanet WASP-39b with JWST NIRCam

Measuring the metallicity and carbon-to-oxygen (C/O) ratio in exoplanet atmospheres is a fundamental step towards constraining the dominant chemical processes at work and, if in equilibrium, revealing planet formation histories. Transmission spectroscopy provides the necessary means by constraining the abundances of oxygen- and carbon-bearing species; however, this requires broad wavelength coverage, moderate spectral resolution, and high precision that, together, are not achievable with previous observatories. Now that JWST has commenced science operations, we are able to observe exoplanets at previously uncharted wavelengths and spectral resolutions. Here we report time-series observations of the transiting exoplanet WASP-39b using JWST's Near InfraRed Camera (NIRCam). The long-wavelength spectroscopic and short-wavelength photometric light curves span 2.0 - 4.0 $\mu$m, exhibit minimal systematics, and reveal well-defined molecular absorption features in the planet's spectrum. Specifically, we detect gaseous H$_2$O in the atmosphere and place an upper limit on the abundance of CH$_4$. The otherwise prominent CO$_2$ feature at 2.8 $\mu$m is largely masked by H$_2$O. The best-fit chemical equilibrium models favour an atmospheric metallicity of 1-100$\times$ solar (i.e., an enrichment of elements heavier than helium relative to the Sun) and a sub-stellar carbon-to-oxygen (C/O) ratio. The inferred high metallicity and low C/O ratio may indicate significant accretion of solid materials during planet formation or disequilibrium processes in the upper atmosphere.Comment: 35 pages, 13 figures, 3 tables, Nature, accepte

A roadmap to the efficient and robust characterization of temperate terrestrial planet atmospheres with JWST

Ultra-cool dwarf stars are abundant, long-lived, and uniquely suited to enable the atmospheric study of transiting terrestrial companions with JWST. Amongst them, the most prominent is the M8.5V star TRAPPIST-1 and its seven planets, which have been the favored targets of eight JWST Cycle 1 programs. While Cycle 1 observations have started to yield preliminary insights into the planets, they have also revealed that their atmospheric exploration requires a better understanding of their host star. Here, we propose a roadmap to characterize the TRAPPIST-1 system -- and others like it -- in an efficient and robust manner. We notably recommend that -- although more challenging to schedule -- multi-transit windows be prioritized to constrain stellar heterogeneities and gather up to 2$\times$ more transits per JWST hour spent. We conclude that in such systems planets cannot be studied in isolation by small programs, thus large-scale community-supported programs should be supported to enable the efficient and robust exploration of terrestrial exoplanets in the JWST era

A broadband thermal emission spectrum of the ultra-hot Jupiter WASP-18b

Close-in giant exoplanets with temperatures greater than 2,000 K (''ultra-hot Jupiters'') have been the subject of extensive efforts to determine their atmospheric properties using thermal emission measurements from the Hubble and Spitzer Space Telescopes. However, previous studies have yielded inconsistent results because the small sizes of the spectral features and the limited information content of the data resulted in high sensitivity to the varying assumptions made in the treatment of instrument systematics and the atmospheric retrieval analysis. Here we present a dayside thermal emission spectrum of the ultra-hot Jupiter WASP-18b obtained with the NIRISS instrument on JWST. The data span 0.85 to 2.85 $\mu$m in wavelength at an average resolving power of 400 and exhibit minimal systematics. The spectrum shows three water emission features (at $>$6$\sigma$ confidence) and evidence for optical opacity, possibly due to H$^-$, TiO, and VO (combined significance of 3.8$\sigma$). Models that fit the data require a thermal inversion, molecular dissociation as predicted by chemical equilibrium, a solar heavy element abundance (''metallicity'', M/H = 1.03$_{-0.51}^{+1.11}$ $\times$ solar), and a carbon-to-oxygen (C/O) ratio less than unity. The data also yield a dayside brightness temperature map, which shows a peak in temperature near the sub-stellar point that decreases steeply and symmetrically with longitude toward the terminators.Comment: JWST ERS bright star observations. Uploaded to inform JWST Cycle 2 proposals. Manuscript under review. 50 pages, 14 figures, 2 table