No abstract

Biomarkers which better match anticancer drugs with cancer driver genes hold the promise of improved clinical responses and cure rates. We developed a precision medicine platform of rapid highthroughput drug screening (HTS) and patient-derived xenografting (PDX) of primary tumor tissue, and evaluated its potential for treatment identification among 56 consecutively enrolled high-risk pediatric cancer patients, compared with conventional molecular genomics and transcriptomics. Drug hits were seen in the majority of HTS and PDX screens, which identified therapeutic options for 10 patients for whom no targetable molecular lesions could be found. Screens also provided orthogonal proof of drug efficacy suggested by molecular analyses and negative results for some molecular findings. We identified treatment options across the whole testing platform for 70% of patients. Only molecular therapeutic recommendations were provided to treating oncologists and led to a change in therapy in 53% of patients, of whom 29% had clinical benefit. These data indicate that in vitro and in vivo drug screening of tumor cells could increase therapeutic options and improve clinical outcomes for high-risk pediatric cancer patients.

Atmospheric dust can influence biogeochemical cycles, accelerate snowmelt, and affect air, water quality, and human health. Yet, the bulk of atmospherically transported material remains poorly quantified in terms of total mass fluxes and composition. This lack of information stems in part from the challenges associated with measuring dust deposition. Here we report on the design and efficacy of a new dry deposition sampler (Dry Deposition Sampling Unit (DSU)) and method that quantifies the gravitational flux of dust particles. The sampler can be used alone or within existing networks such as those employed by the National Atmospheric Deposition Program (NADP). Because the samplers are deployed sterile and the use of water to remove trapped dust is not required, this method allows for the recovery of unaltered dry material suitable for subsequent chemical and microbiological analyses. The samplers were tested in the laboratory and at 15 field sites in the western United States. With respect to material retention, sampler performance far exceeded commonly used methods. Retrieval efficiency was >97% in all trials and the sampler effectively preserved grain size distributions during wind exposure experiments. Field tests indicated favorable comparisons to dust-on-snow measurement across sites (r 2 0.70, p<0.05) and within sites to co-located aerosol data (r 2 0.57-0.99, p<0.05). The inclusion of dust deposition and composition monitoring into existing networks increases spatial and temporal understanding of the atmospheric transport on materials and substantively furthers knowledge of the effects of dust on terrestrial ecosystems and human exposure to dust and associated deleterious compounds.

The Logan River watershed, located in Northern Utah, USA, consists of a relatively pristine, mountainous area that drains to a lower elevation, valley area influenced by both urban development and agriculture. The Logan River Observatory has been collecting aquatic (streamflow and water quality) and climate data throughout the Logan River watershed since 2014. While streamflow measurements are commonly made