To infer the prognostic value of simultaneous androgen receptor (
) and
profiling in liquid biopsies from patients with metastatic castration-resistant prostate cancer (mCRPC) starting a new line of
...signaling inhibitors (ARSi).
Between March 2014 and April 2017, we recruited patients with mCRPC (
= 168) prior to ARSi in a cohort study encompassing 10 European centers. Blood samples were collected for comprehensive profiling of CellSearch-enriched circulating tumor cells (CTC) and circulating tumor DNA (ctDNA). Targeted CTC RNA sequencing (RNA-seq) allowed the detection of eight
splice variants (ARV). Low-pass whole-genome and targeted gene-body sequencing of
and
was applied to identify amplifications, loss of heterozygosity, mutations, and structural rearrangements in ctDNA. Clinical or radiologic progression-free survival (PFS) was estimated by Kaplan-Meier analysis, and independent associations were determined using multivariable Cox regression models.
Overall, no single
perturbation remained associated with adverse prognosis after multivariable analysis. Instead, tumor burden estimates (CTC counts, ctDNA fraction, and visceral metastases) were significantly associated with PFS.
inactivation harbored independent prognostic value HR 1.88; 95% confidence interval (CI), 1.18-3.00;
= 0.008, and outperformed ARV expression and detection of genomic
alterations. Using Cox coefficient analysis of clinical parameters and
status, we identified three prognostic groups with differing PFS estimates (median, 14.7 vs. 7.51 vs. 2.62 months;
< 0.0001), which was validated in an independent mCRPC cohort (
= 202) starting first-line ARSi (median, 14.3 vs. 6.39 vs. 2.23 months;
< 0.0001).
In an all-comer cohort, tumor burden estimates and
outperform any
perturbation to infer prognosis.See related commentary by Rebello et al., p. 1699.
One of the key repercussions of the desertification process in the Sahara and the Arabian desert is increased aeolian sand drift and sand deposition. Despite its isolated location and severe desert ...climate—particularly in terms of solar radiation, sand drift, and sand deposition—the region of El-Oued Souf in the Grand Erg Oriental in the Algerian Sahara has been a key cultural and trade center for many centuries. To resist the extreme weather conditions, the architecture of the vernacular settlements in the region of El-Oued Souf has unique design traits. Newly constructed buildings, on the other hand, frequently employ technologies based on models imported or imposed from climates that bear little resemblance to the desert. As a result, the inhabitants of these structures live more ‘in the desert’ than ‘with the desert’. This study investigates the impact and the effectiveness of vernacular desert architecture to resist aeolian sand encroachment problems in sandy desert areas. The sand accumulation patterns around vernacular buildings were identified and quantified using wind tunnel experiments. The size and shape of the buildings, as well as their geometric configuration within the settlement, were investigated in relation to the shape and dimension of sand accumulation formations. Field observations in north Algeria and the United Arab Emirates confirmed the accumulation patterns produced by the wind tunnel experiments. The study proposes possible design indicators for building forms to minimize the impact of sand deposition on such forms.
Wind tunnel experiments were conducted to investigate the relationships between vertically settling dust and the horizontal dust flow from which the particles originate. The study primarily focused ...on the grain size characteristics and on the horizontal and vertical sediment fluxes. Simultaneous samplings of vertical deposition flux and horizontal transport flux were carried out at an almost identical altimetric level (a very narrow layer immediately above a water surface generating no resuspension). This made it possible to relate deposition flux to the horizontal transport flux and to study how deposition alters the sedimentological characteristics of horizontally moving dust. The use of water as a deposition surface implied that the dust was subjected to some degree of dispersion after the settling. This restricted the analysis to grains >10 μm, but the trends for grains <10 μm were easy to reconstruct. The experiments show that deposited dust is generally coarser than the parent dust from which it originates but only for friction velocities below 0.34 m s−1. For higher wind speeds the median grain diameter of settling dust does not differ from that of the parent dust. Similar observations were made for the horizontal and vertical dust fluxes. At a constant horizontal transport flux (Fh) vertical deposition flux (Fs) drops with wind speed; however, from the same critical friction velocity of 0.34 m s−1 the ratio Fs/Fh remains constant. It was also found that the relationships between Fh and Fs depend on the grain size of the particles but only for sufficiently fine particles. Particles >50 μm no longer affect these relationships. Vertical mixing created by the turbulent nature of the flow strongly affects deposition of atmospheric dust. Mixing significantly hampers deposition of the grains, especially the small ones. The wind tunnel experiments allowed the magnitude of the effect mixing exerts on deposition to be calculated. For coarse grains the effect is small, but for fine grains mixing may hamper deposition by several dozen per cent. Theoretical dust deposition models should thus consider vertical mixing or otherwise include it in the numerical value of the velocity of deposition vd.
•Wind tunnel protocol to test anti-soiling coatings and anti-reflective coatings.•Effect of coatings on pollution of PV surfaces.•Effect of coatings on cleaning of PV surfaces.•Effect of coatings on ...optical transmittance.
A wind tunnel protocol is presented that allows to study the efficiency of anti-soiling and anti-reflective coatings under dry soiling conditions. Anti-soiling coatings are intended to reduce the accumulation of dust on photovoltaic modules and other surfaces. Dust accumulation is the combined result of sedimentation (or deposition) and syngenetic or post-genetic removal. In the field, the amount of dust present on a photovoltaic surface is always the result of accumulation. The protocol allows one to study the effects of anti-soiling and anti-reflective coatings on the processes of dust deposition and dust removal separately so that the specific operation of the coatings in comparison to uncoated glass can be better understood. Using an aeolian dust wind tunnel, dust deposition and dust removal measurements were performed under quasi-natural conditions on surfaces with and surfaces without an anti-soiling coating. Optical transmittance measurements were performed to determine the impact of anti-soiling and anti-reflective coatings on the amount of light passing through dust-polluted surfaces. We illustrate the protocol by comparing anti-soiling and anti-reflective coated surfaces with identical uncoated surfaces. The anti-soiling coating that was tested in this study has a dual functionality as it has both anti-soiling and anti-reflective properties. Results showed that the tested coatings did not affect the sedimentation of dust, but they did have a significant effect on dust removal, which started at a lower wind speed and cleaned the surface more rapidly compared to the uncoated surface. Additionally, the anti-soiling coating outperformed the anti-reflective coating regarding the wind speed at which dust removal started, indicating that dust adhesion forces on the anti-soiling coating are lower. Transmittance was always higher for the coated surfaces than for the uncoated surface, but the benefit of the coatings (higher transmittance) decreased as the glass surfaces became more polluted with dust.
Soil analyses and measurements with the Portable In Situ Wind Erosion Laboratory (PI-SWERL) were conducted on 16 soil types in an area heavily affected by off-road vehicle (ORV) driving. Measurements ...were performed in ORV trails as well as on undisturbed terrain to investigate how ORV driving affects the vulnerability of a soil to emit PM10 (particles
<
10
μm), during the driving as well as during episodes of wind erosion. Particular attention is paid to how the creation of a new trail affects those properties of the topsoil that determine its capability to emit PM10. Also, recommendations are given for adequate management of ORV-designed areas. The type of surface (sand, silt, gravel, drainage) is a key factor with respect to dust emission in an ORV trail. Trails in sand, defined in this study as the grain size fraction 63–2000
μm, show higher deflation thresholds (the critical wind condition at which wind erosion starts) than the surrounding undisturbed soil. Trails in silt (2–63
μm) and in drainages, on the other hand, have lower deflation thresholds than undisturbed soil. The increase in PM10 emission resulting from the creation of a new ORV trail is much higher for surfaces with silt than for surfaces with sand. Also, the creation of a new trail in silt decreases the supply limitation in the top layer: the capacity of the reservoir of emission-available PM10 increases. For sand the situation is reversed: the supply limitation increases, and the capacity of the PM10 reservoir decreases. Finally, ORV trails are characterized by a progressive coarsening of the top layer with time, but the speed of coarsening is much lower in trails in silt than in trails in sand or in drainages. The results of this study suggest that, to minimize emissions of PM10, new ORV fields should preferably be designed on sandy terrain rather than in silt areas or in drainages.
Amphibole asbestos minerals are known human carcinogens, and many regulations have been developed to limit occupational exposure. These minerals can also occur in the natural environment, where they ...may be more difficult to control. We applied a diverse set of analytical methods including scanning electron microscopy/energy dispersive spectroscopy, electron probe analysis, x‐ray diffraction, and field‐emission scanning electron microscopy to rock, soil, and dust samples and to particles attached to clothing samples and cars. We found naturally occurring fibrous actinolite, a regulated amphibole asbestos mineral, in rock, soil, and dust that can be transported by wind, water, cars, or on clothing after outdoor recreational activities. Sources of these fibrous amphiboles are several plutons in southern Nevada and Arizona and alluvial fans emanating from asbestos‐containing bedrock. The morphology of the amphibole fibers is similar to amphibole fibers found in the USEPA Superfund site at Libby, MT. We found that the morphometry of the fibrous particles in the study area did not substantially change when the original bedrock weathered into soil, and particles were eroded and transported through wind and/or water and finally settled and accumulated on natural or other surfaces. Because large populations in Boulder City, Henderson, and Las Vegas are located only a few kilometers, sometimes even only a few tens of meters, downwind from the sources, and because most of the particles are transported in suspension after they are emitted, potentially large populations in Boulder City, Henderson, and perhaps Las Vegas could be exposed. This study demonstrates a potential public health risk to several large population areas.
Field experiments were conducted in Nellis Dunes Recreational Area (Clark County, Nevada, USA) to investigate emission of dust produced by off-road driving. Experiments were carried out with three ...types of vehicles: 4-wheelers (quads), dirt bikes (motorcycles) and dune buggies, on 17 soil types characteristic for a desert environment. Tests were done at various driving speeds, and emissions were measured for a large number of grain size fractions. This paper reports the results for two size fractions of emissions: PM10 (particles <
10 μm) and PM60 (particles <
60 μm). The latter was considered in this study to be sufficiently representative of the total suspendable fraction (TSP). Off-road driving was found to be a significant source of dust. However, the amounts varied greatly with the type of soil and the characteristics of the top layer. Models predicting emission of dust by off-road driving should thus consider a number of soil parameters and not just one key parameter. Vehicle type and driving speed are additional parameters that affect emission. In general, 4-wheelers produce more dust than dune buggies, and dune buggies, more than dirt bikes. Higher speeds also result in higher emissions. Dust emitted by off-road driving is less coarse than the parent sediment on the road surface. Off-road driving thus results in a progressive coarsening of the top layer. Exceptions to this are silty surfaces with no, or almost no, vegetation. For such surfaces no substantial differences were observed between the grain size distribution of road dust and emitted dust. Typical emission values for off-road driving on dry desert soils are: for sandy areas, 30–40 g km
−
1
(PM10) and 150–250 g km
−
1
(TSP); for silty areas, 100–200 g km
−
1
(PM10) and 600–2000 g km
−
1
(TSP); for drainages, 30–40 g km
−
1
(PM10) and 100–400 g km
−
1
(TSP); and for mixed terrain, 60–100 g km
−
1
(PM10) and 300–800 g km
−
1
(TSP). These values are for the types of vehicles tested in this study and do not refer to cars or trucks, which produce significantly more dust.
Current farm systems rely on the use of Plant Protection Products (PPP) to secure high productivity and control threats to the quality of the crops. However, PPP use may have considerable impacts on ...human health and the environment. A study protocol is presented aiming to determine the occurrence and levels of PPP residues in plants (crops), animals (livestock), humans and other non-target species (ecosystem representatives) for exposure modelling and impact assessment. To achieve this, we designed a cross-sectional study to compare conventional and organic farm systems across Europe. Environmental and biological samples were/are being/will be collected during the 2021 growing season, at 10 case study sites in Europe covering a range of climate zones and crops. An additional study site in Argentina will inform the impact of PPP use on growing soybean which is an important European protein-source in animal feed. We will study the impact of PPP mixtures using an integrated risk assessment methodology. The fate of PPP in environmental media (soil, water and air) and in the homes of farmers will be monitored. This will be complemented by biomonitoring to estimate PPP uptake by humans and farm animals (cow, goat, sheep and chicken), and by collection of samples from non-target species (earthworms, fish, aquatic and terrestrial macroinvertebrates, bats, and farm cats). We will use data on PPP residues in environmental and biological matrices to estimate exposures by modelling. These exposure estimates together with health and toxicity data will be used to predict the impact of PPP use on environment, plant, animal and human health. The outcome of this study will then be integrated with socio-economic information leading to an overall assessment used to identify transition pathways towards more sustainable plant protection and inform decision makers, practitioners and other stakeholders regarding farming practices and land use policy.
In aeolian research, field measurements are important for studying complex wind-driven processes for land management evaluation and model validation. Consequently, there have been many devices ...developed, tested, and applied to investigate a range of aeolian-based phenomena. However, determining the most effective application and data analysis techniques is widely debated in the literature. Here we investigate the effectiveness of two different sediment traps (the BEST trap and the MWAC catcher) in measuring vertical sediment flux. The study was performed in a wind tunnel with sediment fluxes characterized using saltiphones. Contrary to most studies, we used the analogue output of five saltiphones mounted on top of each other to determine the total kinetic energy, which was then used to calculate aeolian sediment budgets. Absolute sediment losses during the experiments were determined using a balance located beneath the test tray. Test runs were conducted with different sand sizes and at different wind speeds. The efficiency of the two traps did not vary with the wind speed or sediment size but was affected by both the experimental setup (position of the lowest trap above the surface and number of traps in the saltation layer) and the technique used to calculate the sediment flux. Despite this, good agreement was found between sediment losses calculated from the saltiphone and those measured using the balance. The results of this study provide a framework for measuring sediment fluxes at small time resolution (seconds to milliseconds) in the field.
The few loci associated with multiple sclerosis (MS) are all related to immune function. We report a GWA study identifying a new locus replicated in 2,679 cases and 3,125 controls. An rs10492972C ...variant located in the KIF1B gene was associated with MS with an odds ratio of 1.35 (P = 2.5 × 10−10). KIF1B is a neuronally expressed gene plausibly implicated in the irreversible axonal loss characterizing MS in the long term.
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