Search

[Display omitted] • We compare the in vitro lung toxicity of ground tire particles (TP) and actual TRWP. • In addition to tire tread material, TRWP include road wear inclusions, dust, etc. • TP and TRWP showed a similar profile: no cytotoxicity or oxidative stress induced. • But both triggered a concentration-dependent proinflammatory response. • The pulmonary toxicity of TRWP may be mainly due to the tire tread material. There is currently limited data on the potential effects of tire and road wear particles (TRWP) on human health. TRWP include tire fragments, but also road wear materials, dust, adsorbed gaseous pollutants and different types of inclusions that could affect their hazard profiles. Due to their availability and lower complexity, ground tire particles (TP) are often used in toxicological studies. However, this makes it difficult to draw firm conclusions about the potential hazard of actual TRWP. Here, we compared the in vitro toxicological profile of ground TP and actual TRWP emissions of similar size collected from road traffic. For this purpose, TP and TRWP were separately incubated with alveolar macrophages for 24 h, and the cellular response was evaluated in terms of cytotoxicity, proinflammatory response and oxidative stress. Both TP and TRWP induced neither significant cytotoxicity nor oxidative stress, but triggered a concentration-dependent proinflammatory response, as evidenced by increased TNF-α production. The level of TNF-α production was slightly higher with TRWP than with TP, independent of the particle dose. All in all, the pulmonary toxicity of TRWP could be due primarily to the tire tread inclusions and only marginally to other particle components (i.e. road wear materials, dust ...). Although these preliminary results need to be confirmed by further analysis, they could be useful for tire manufacturers in the production of safer-by-design tires. [ABSTRACT FROM AUTHOR]

Objective: Bosutinib, nilotinib and dasatinib are approved for the treatment of patients with newly diagnosed chronic-phase chronic myeloid leukemia (CP-CML). In the absence of head-to-head comparisons between second-generation tyrosine kinase inhibitors (TKIs), the objective of this study was to indirectly compare the efficacy of bosutinib with nilotinib and dasatinib in first-line (1L) CP-CML.Methods: Cross-trial heterogeneity in terms of patient baseline characteristics and imatinib dose escalation are difficult to adjust for in network meta-analyses and anchored matching-adjusted indirect treatment comparisons (MAICs). Therefore, an unanchored MAIC was performed using patient level data from bosutinib (BFORE trial) and published aggregated data from nilotinib (ENESTnd) and dasatinib (DASISION) trials. After matching, cytogenetic and molecular responses, and disease progression, after a minimum follow-up of 24 months were compared between nilotinib versus bosutinb and dasatinib versus bosutinib.Results: The comparison of nilotinib versus bosutinib resulted in no statistically significant differences for MMR at and by 24 months, MR4 by 24 months, MR4.5 at and by 24 months, CCyR by 24 months, and disease progression, however, a decreased odds of MR4 at 24 months in favor of bosutinib versus nilotinib was observed. The comparison of dasatinib versus bosutinib by 24 months resulted in no statistically significant differences for MMR, disease progression, and CCyR, however a decreased odds of MR4.5 in favor of bosutinib versus dasatinib was observed.Conclusions: Overall, in these analyses bosutinib demonstrates equivalent efficacy to nilotinib and dasatinib in the treatment of patients with newly diagnosed CP-CML. [ABSTRACT FROM AUTHOR]

This study aims to examine tire and road wear particle (TRWP) emissions under realistic conditions in order to provide some valuable insights into understanding their sources and fate in the environment. TRWP emissions were evaluated with a fully instrumented vehicle driving on five representative road types: urban, ring road, suburban, highway, and rural. Multiple vehicle dynamic variables were recorded to assess the factors influencing these emissions. For the first time, emitted particles were collected on filters and analyzed by means of pyrolysis coupled with gas chromatography-mass spectrometry to determine the polymeric content of tires, in specifically quantifying styrene-butadiene rubber (SBR) and butadiene rubber (BR) pyrolytic markers. The measurements obtained from the five road types revealed similar size distributions for SBR + BR emissions, with maxima found in the (ultra)fine fraction (< 0.39 µm). Upon applying an SBR + BR-to-TRWP conversion factor, (ultra)fine fraction TRWP emissions proved to be the highest for suburban (64 ± 5 µg/km), followed by highway, urban, ring road and rural routes. The output represents up to 480 tons of TRWP per year emitted in the EU 27 , thus suggesting a widely impregnated atmospheric compartment capable of threatening human health. Furthermore, an analysis of variables revealed that acceleration, tire constraints, and constant sustained driving factors had specific impacts on TRWP emissions. [Display omitted] • Tire and road wear particle emissions were assessed using an instrumented vehicle. • A new approach was used to quantify realistic SBR+BR emissions by pyrolysis-GC-MS. • The size distribution by mass of SBR+BR was higher in the fraction < 0.39 µm. • Total TRWP emissions can reach as high as 78 ± 8 µg/km depending on the road type. • Dynamic driving conditions explain the emission of TRWP. [ABSTRACT FROM AUTHOR]

Objective: In clinical trials of second-line therapies for chronic phase chronic myeloid leukemia (CP-CML), to date, only single-arm trials have been conducted for the available tyrosine kinase inhibitor treatments (bosutinib, dasatinib and nilotinib). These trials included heterogeneous patient populations in terms of disease and baseline characteristics. These hamper the use of standard network meta-analyses for indirect treatment comparison of relative efficacy. In this situation, a matching-adjusted indirect comparison (MAIC) in second-line CP-CML was performed. The aim was to compare the relative efficacies of bosutinib, dasatinib and nilotinib in second-line CP-CML patients.Methods: The MAIC was preceded by a systematic literature review that ensured inclusion of the underlying data for the analyses. The outcomes were measured in terms of overall survival (OS), progression-free survival (PFS) and major cytogenetic response (MCyR). The treatments were quantitatively compared based on Cox proportional hazard ratio (HR) regressions, on restricted mean survival (RMST, when the proportionality assumption showed evidence of violation) and on odds ratios (for response measures).Results: Comparing with dasatinib, bosutinib resulted in HRs for PFS and OS of 0.63 (0.44-0.90, p < .05) and 0.82 (0.54-1.26, p = .37) respectively, and resulted in an OR for MCyR of 0.78 (0.53-1.16). Although the proportionality of hazards assumption was violated for PFS, the RMST analyses confirmed the findings of the Cox regression. When compared with nilotinib, bosutinib showed a significant HR of 0.54 (0.38-0.76, p < .01) in favor of bosutinib for PFS, a non-significant HR of 0.72 (0.46-1.13, p = .16) for OS and a non-significant OR of 0.98 (0.71-1.35) for MCyR.Conclusions: Bosutinib had a significantly greater PFS than both dasatinib and nilotinib. For OS, the findings were numerically in favor of bosutinib, but not statistically significant. For MCyR, the findings were numerically in favor of dasatinib and nilotinib, but not statistically significant. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Particulate pollution was evaluated both inside and outside of public rapid transits. • No systematic air quality gains could be attributed to public rapid transit systems. • Air quality at the users' scale depended on the indoor accumulation of outdoor pollution and in-vehicle PM generation. • Enforcing standards does not ensure a reduced lung accumulation, and vice versa. • In densely trafficked areas, it is preferable for pedestrians to use the available public transport system. Abstract Airborne particulate matter (PM) and particle-bound polycyclic aromatic hydrocarbons (PAHp) were monitored both inside and outside of a tramway and two types of high-level service buses within a major French conurbation. The air quality variations among tramway and the different bus rapid transit systems were large and significant. This proved to be a complex issue involving contamination and clearance processes, as evidenced by mechanisms like in-vehicle PM generation and indoor accumulation of the outdoor PAHp pollution. Given these empirical results, a simple lung-accumulation model has been formulated in order to estimate the public transport users' (PTU) exposure during their journey. Calculations draw attention to situations and categories of individuals to be targeted by clean air policies. For instance, despite being chronically exposed to excessive concentrations in heavily built-up and trafficked areas, PTU would accumulate in their lungs 4–11 times less PM and PAHp than nearby pedestrians walking the same route. These pedestrians are more likely to experience short episodes of strong lung accumulations. Moreover, the numerical approach employed herein allowed: (i) estimating a distance at which walking could be considered a viable alternative to the use of public transport services; (ii) probing the relevance (in terms of lung accumulations) of both EU and US standards; and (iii) proposing exposure reduction strategies. [ABSTRACT FROM AUTHOR]

This study investigated, on both metric and centimetric scales, mercury (Hg) transformations and dynamics within a water column chemocline of a tropical reservoir. Data collected included conventional measurement of Hg in water samples, diffusive gradients in thin-films (DGT) assessments, and thermodynamic speciation modeling in order to portray the biogeochemical processes that control elemental Hg (EM) and dissolved monomethylated Hg (MeHg D ) production. The primary contribution of this study is demonstration that the DGT technique can be successfully implemented to examine labile Hg compound mobilization, and estimation of how local substratum facilitates Hg reduction and methylation reactions. DGT profiles with a resolution of 1 cm revealed a fine sequence of prominent Hg reduction/oxidation reactions at the chemocline level. This is interpreted as a manifestation of both: i) kinetic effects capable of arising inside the diffusive layer of DGT devices, and ii) extremely localized production or consumption of reducible and methylable Hg. Another key result obtained at the metric scale is that EM and MeHg D production at a water column chemocline are intricately linked, as both are fueled by nutrients episodically released during the decomposition of falling epilimnetic organic particles or inhibited by dissolved organic matter and inorganic compounds continuously transported from the deeper monimolimnion. Finally, it is worth noting that the chemocline acts as an accumulation and recycling domain for falling MeHg-loaded organic particles, whereas the high primary productivity layer in the epilimnion represents the principal reactor with respect to Hg methylation and reduction. [ABSTRACT FROM AUTHOR]

Roadside contamination (of air, soils and organisms) by polycyclic aromatic hydrocarbons (PAHs) was examined in an arable field and a mature forest (central France). Measured contents accounted for minute fractions of the cumulative vehicular exhaust emissions. The fate of vehicular PAHs was affected by many factors, including: atmospheric load dispersal, deposition on soils and vegetation, incorporation into water and organic matter cycles, and accumulation in species. Given these empirical results, we evaluated the consistency of a set of well-known diagnostic ratios. This effort has revealed that: i) most diagnostic ratio values vary considerably across roadside samples, including exhaust emissions; and ii) the first few meters from the carriageway or the road verge/forest interface or remote areas where surface water accumulates actually define turning or inflection points in the ratio profiles. These variations constitute a major obstacle to delimitating the extent of roadside contamination due to PAHs, in addition to raising questions over the applicability of ratios routinely used to designate sources. New ratios, namely (Flt + BkF)/(Pyr + BbF) and (Flt + BkF + BghiP)/Σ 10 PAH, have been specifically developed to address this challenge. The higher consistencies exhibited among environmental compartments as well as between surface soil and exhaust emissions still yield differentiated values relative to several industrial sources. [ABSTRACT FROM AUTHOR]

This study focuses on the actual exhaust emissions of regulated and unregulated pollutants from earthwork machines (EM). In addition to providing a realistic assessment of gaseous and particulate emissions from key EM and filling critical data gaps in emission inventories, it emphasizes the importance of breaking down the average operating emission factors into task-related emission factors (TEF). The latter serve many goals, namely by: categorizing EM in relation to their emission dynamics, finding emission determinants and proposing on-site emission mitigation strategies. These have also led to a more refined analysis of both the effectiveness of EU and US emissions standards and the accuracy of NONROAD2008 model. Ultimately, by using task-related emission factors in conjunction with data available from the literature and with the methodology developed by US-EPA, a lower bound was estimated for gaseous exhaust emissions from the major construction vehicles operable at earthwork sites. [ABSTRACT FROM AUTHOR]

This paper presents the identification of a miniature coaxial helicopter system. First, the helicopter flying principles are described and the hardware setup of the developed platform is presented. Further, linear models are developed for the movements of the helicopter using prediction error identification methods. The results in this case are accurate and can be used for performant controller design in some operating points. But in order to model the complete dynamics of the helicopter, nonlinear models are developed using recurrent dynamic neural networks. In this case the models obtained present a higher accuracy compared with the linear case and also with the results published until now. In the end, the advantages of nonlinear modeling based on neural networks is emphasized and some conclusions are drawn. [ABSTRACT FROM AUTHOR]

Straining depicts the geometrical retention of fine particles within materials' pore network. Whether or not fines can be retained depends on (1) the structure of materials' pore network as well as (2) fines' size distribution, manner of deposition, and retained amount. In this paper, the main results of straining tests are presented for randomly packed beads filters. The experimental program included a series of tests performed in both dry and water-saturated filters. The tests provided information on the dynamics of fines in the filters' pore network and changes of filters' efficiency. For instance, data supported the existence of four distinct stages: the filling of accessible cavities, the formation then clogging of the preferential pathways, the transfer of fines toward the lateral unobstructed capillaries, and eventual formation of a surface cake. The postulated mechanisms inherent to every single stage are discussed in terms of retention rate, straining length, lateral transfer, and progressive obstruction of constrictions. Additionally, the straining mechanisms were also probed in hydrodynamic conditions at increasing water flows. [ABSTRACT FROM AUTHOR]

Summary: Internal erosion (IE) of chemically reinforced granular materials results in dislodgement of particles from their rigid skeleton due to seepage stresses. Whether or not these particles can be dislodged and flushed out by seepage depends on (i) the amount of binding agent used to reinforce the granular matrix, (ii) the structure of pore network and (iii) severity of seepage stresses. Results of IE tests are presented for compacted-sand reinforced with increasing amounts of silica gel. The silica gel is a binding agent that permits low-permeability materials reinforcement. IE tests provided information about eroded particles, macro/micro-structural changes and indicators of ongoing IE mechanisms. For instance, data highlighted the existence of up to three IE stages. This includes flushing of movable particles, binder removal and subsequent releases then self-filtering of fine particles within the rigid skeleton. From the careful monitorings of effluent particles (in terms of concentrations and sizes), it was possible to gauge the dynamics of binder removal. Besides, it was also possible to follow changes in dimensions of the smallest constriction that drives travel distances of dislodged particles. [ABSTRACT FROM AUTHOR]

Abstract: Dissolved organic matter (DOM) samples were obtained from a low-density urbanized area located upstream of Paris (along the Marne River, France) and from the treated effluents at the Paris main wastewater treatment plant. These samples were then fractionated according to their hydrophobicity. DOM fractions consisted of nanomolar to sub-micromolar fresh organic substances with extremely strong Hg-complexing ligands. The conditional stability constants (i.e. ; pH∼6.8, I NaCl =0.5M, T =25°C) of the Hg-DOM complexes formed were greater than 1024 M−1, for the reaction Hg2+ +L=HgL (with L as ligand). For upstream of Paris, thermodynamic calculations indicated that the vast majority of Hg-DOM was associated with hydrophobic DOM. In contrast, in the Paris main wastewater treatment plant effluents, Hg-DOM was mainly bound to hydrophilic DOM. Simple dilution calculations highlighted that due to the large DOM loading of urban discharges, the hydrophilic urban DOM ligands may commonly dominate Hg-DOM speciation in the downstream Seine River, except under extreme dilution (i.e. high water episodes or floods). [Copyright &y& Elsevier]

Abstract: The distribution and speciation of mercury (Hg) in the water column, the inputs (wet deposition and tributaries) and the outputs (atmospheric evasion and outlet) of an artificial partially anoxic tropical lake (Petit-Saut reservoir, French Guiana) were investigated on a seasonal basis in order to appraise the cycling and transformations of this metal. The total mercury (HgT) concentrations in the oxygenated epilimnetic waters averaged 5±3pmolL−1 in the unfiltered samples (HgTUNF) and 4±2pmolL−1 in the dissolved (HgTD) phase (<0.45μm). On average, the monomethylmercury (MMHg) constituted 8%, 40% and 18% of the HgT in the dissolved phase, the particulate suspended matter and in the unfiltered samples, respectively. Covariant elevated concentrations of particulate MMHg and chlorophyll a in the epilimnion suggest that phytoplankton is an active component for the MMHg transfer in the lake. In the anoxic hypolimnion the HgTUNF averages 13±6pmolL−1 and the HgTD 8±4pmolL−1. The averages of MMHgP and MMHgD in hypolimnetic waters were two and three times the corresponding values of the epilimnion, 170±90pmolg−1 and 0.9±0.5pmolL−1, respectively. In the long dry and wet seasons, at the flooded forest and upstream dam sampling stations, the vertical profiles of MMHgD concentrations accounted for two distinct maxima: one just below the oxycline and the other near the benthic interface. Direct wet atmospheric deposition accounted for 14molesyr−1 HgTUNF, with 0.7molesyr−1 as MMHgUNF, while circa 76molesyr−1 of HgTUNF, with 4.7molesyr−1 as MMHgUNF, coming from tributaries. Circa 78moles (∼17% as MMHg) are annually exported through the dam, while 23molesyr−1 of Hg0 evolve in the atmosphere. A mass balance calculation suggests that the endogenic production of MMHgUNF attained 8.1molesyr−1, corresponding to a methylation rate of 0.06%d−1. As a result, the Petit-Saut reservoir is a large man-made reactor that has extensively altered mercury speciation in favor of methylated species. [Copyright &y& Elsevier]

Elemental mercury (Hg°) for gold amalgamation is the main process applied by artisanal gold miners in South America, leading to important discharges into freshwater ecosystems. Through a 28-day experimental approach based on indoor microcosms, we simulated the chemical fate and bioavailability of Hg° droplets in the presence or absence of sediment collected from a typical forest creek that is unaffected by gold mining activities. Our results clearly showed significant mercury transfers in the water column in both the dissolved gaseous Hg° and oxidized (Hg(II)) forms, with a marked effect of the presence of sediment. After 28 days, Hg total (HgT) concentration in the water column was 25 times higher in sediment-free units (108 ± 17 vs 4 ± 0.4 nM). Methylmercury (MeHg) determinations in the dissolved fraction showed a significant increase only in the presence of sediment after 7 and 14 days. Zebrafish (Danio rerio) were used as indicators for mercury bioavailability. The HgT determinations in four organs revealed significant accumulation levels as early as 7 days exposure, with marked differences in favor of fish collected from the sediment-free units. Significant MeHg increases were observed in the four organs only when sediment was present. Genomic tools applied to estimate sulfate-reducing bacteria communities showed mercury impacts on their diversity and distribution in the different compartments (water, sediment, biofilm, fish gut). [ABSTRACT FROM AUTHOR]

Non-exhaust emissions are now recognized as a significant source of atmospheric particulate matter and the trend towards a reduction of conventionally fueled internal combustion engine vehicles on the road is increasing their contribution to air pollution due to lower exhaust emissions. These particles include brake wear particles (BWP) and tire-road contact particles (TRCP), which are composed of tire wear particles (TWP), road wear particles (RWP) and resuspended road dust (RRD). The goal of this study has therefore been to design an original experimental approach to provide insight into the chemical composition of particles emitted at the tire-road contact, focusing on the micron (PM 10–1μm) and submicron (PM 1–0.1μm) fractions. Through this characterization, an examination of the different TRCP generated by different materials (tire, road surface, brake system) was conducted. To achieve this, TRCP were collected at the rear of the wheel of an instrumented vehicle during road and track tests, and a SEM-EDX analysis was performed. Our experimental conditions have allowed us to demonstrate that, at the individual particle scale, TRCP are consistently associated with road dust materials and particles solely composed of tire or road materials are practically non-existent. The contribution of BWP to TRCP is marked by the emission of Fe-rich particles, including heavy metals like Ba, Mn and Cr. TWP, which result from rubber abrasion, consist of C-rich particles abundant in Si, Zn, and S. RWP, mainly composed of Al, Si, Fe, and Ca, can be either part of RRD or internally mixed with emitted TWP. The findings of this study highlight the substantial role of RRD to TRCP emissions under real driving conditions. Consequently, it underscores the importance of examining them simultaneously to achieve a more accurate estimation of on-road traffic emissions beyond the vehicle exhaust. [Display omitted] • Tire Road Contact Particles (TRCP) can be classified according to their chemical composition to identify their origins. • Brake wear particles are Fe-rich particles and also contain tracers such as Ba or Mn. • Tire wear particles are carbonaceous particles containing Si, Zn, and S. • Mineral incrustation, from road wear/dust, are often embedded in the tire tread. • At the individual particle scale, TRCP are mostly contaminated by road dust. [ABSTRACT FROM AUTHOR]

Accumulation of heavy metals can occur on clay barriers or slurry-trench cutoff wall, resulting in their high concentrations at which the retention reaction takes place. Or high concentration conditions are often adopted to accelerate the reaction process at a laboratory scale for investigating their impacts on engineering behaviors (hydraulic or mechanical) of clays. So far, there is lack of data regarding heavy metal retention behavior on clays under those extreme concentration conditions. This paper aims to mitigate this gap with emphasis on pH effects. To do so, several series of sorption batch tests were conducted to characterize the retention capacity of three ubiquitous heavy metals (Pb, Zn and Cu) on two reference clays (Speswhite kaolin and Wyoming bentonite). A wide range of individual metal concentration varying from 0.1 to 100 mM and different pH conditions were tested. Results suggest that the acidifying the metal–clay system can result in a significant decrease in the heavy metal retention, which can be attributed to an increase in competition of H + with metal ions to the surface sites and a decrease in metal ion precipitation as hydroxides at high pH levels. In addition, the heavy metal retention isotherm over a wide range of concentrations for the bentonite follows Temkin and Langmuir adsorption models while Freundlich and Langmuir models for the kaolin. Interestingly, at a high concentration of 10 mM, the Pb precipitation unlikely occurs in the presence of both clays tested over a wide range pH level (< 10), whereas it likely takes place in case of Cu and Zn. [ABSTRACT FROM AUTHOR]

SUMMARY Internal erosion (IE) affects the stability of natural and reinforced materials by causing instability within their granular structure. The dislodgement and transport of eroded particles affect both the particulate concentration of eroding fluid and the pore network of eroded material. In this study, we examined these modifications using a transport model with a finite element code. First, IE tests on chemically reinforced sand columns were performed to obtain information about eroded material loss of mass, particulate concentration of effluent, porosity and permeability modifications, and existing IE stages. Second, based on experimental results, a mathematical one-dimensional model has been formulated to monitor the evolution and spatial distribution of erodible solids, fluidized particles, porosity, permeability, and seepage stresses. The model consists of a set of coupled nonlinear differential equations solved in sequence. It provides valuable information about the extent and the dynamics of structural changes, which can be used to estimate an IE time for the hydraulic work to reach failure. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The Petit-Saut hydroelectric reservoir was filled in 1994 on the Sinnamary River in French Guiana (Amazonian basin). Flooding of the equatorial rain forest led to anoxia in most of the water column and enhanced mercury methylation in the reservoir hypolimnion. We selected the benthivorous/omnivorous fish species Curimata cyprinoides to investigate total mercury and methylmercury (MeHg) bioavailability and bioaccumulation capacities in the reservoir and downstream in the Sinnamary River. Mercury concentrations in the dorsal skeletal muscle were 10-fold higher in fish from the downstream zone. Stomach contents and stable nitrogen and carbon isotope ratios showed that biofilms and the associated invertebrate communities represented important food sources at the two sites. The δ13C measurements indicated that biofilms in the flooded forest zone of the reservoir consist of endogenous primary producers; downstream, they are based on exogenous organic matter and microorganisms, mainly from the anoxic layers of the reservoir. Total mercury and MeHg concentrations in the biofilms and associated invertebrates were much higher at the downstream site compared to concentrations at the reservoir. Our results clearly show the importance of MeHg export from the anoxic layers of this tropical reservoir. We conclude that differences between biofilm composition and MeHg concentrations in the ingested food could explain the marked differences observed between mercury levels in fish. [ABSTRACT FROM AUTHOR]

Summary: Bortezomib is a first‐in‐class proteasome inhibitor, approved for the treatment of multiple myeloma. The originally approved dosing schedule of bortezomib results in significant toxicities that require dose interruptions and discontinuations. Consequentially, less frequent dosing has been explored to optimise bortezomib's benefit–risk profile. Here, we performed exposure–response analysis to compare the efficacy of the original bortezomib dosing regimen with less frequent dosing of bortezomib over nine 6‐week treatment cycles using data from the VISTA clinical trial and the control arm of the ALCYONE clinical trial. The relationship between cumulative bortezomib dose and clinical response was evaluated with a univariate logit model. The median cumulative bortezomib dose was higher in ALCYONE versus VISTA (42·2 vs. 38·5 mg/m2) and ALCYONE patients stayed on treatment longer (mean: 7·2 vs. 5·8 cycles). For all endpoints and regimens, probability of clinical response correlated with cumulative bortezomib dose. Similar to results observed for VISTA, overall survival was longer in ALCYONE patients with ≥ 39·0 versus < 39·0 mg/m2 cumulative dose (hazard ratio, 0·119; P < 0·0001). Less frequent bortezomib dosing results in comparable efficacy, and a higher cumulative dose than the originally approved bortezomib dosing schedule, which may be in part be due to reduced toxicity and fewer dose reductions/interruptions. [ABSTRACT FROM AUTHOR]

When designing field development plans for hydrocarbon exploitation, most often the reservoirs models model rocks which allow flow of the fluids contained in their pores. A reservoir can be defined as a single hydrodynamic unit. The quality of the rocks in this hydrodynamic unit will vary and is usually a function of the depositional environment, diagenesis, etc. The different rock qualities are characterized by different pore sizes and geometries which will allow the water to rise due to capillarity phenomena. This creates a transition zone which is heterogeneous as the reservoir rock is. When we are reporting volumes in place we usually define them at the contact. What do we understand by contact and how is the rock quality or heterogeneity affecting the volumes in place are the questions that we are going to address in this article with the use of a simple "layer cake" ECLIPSE simulation model. [ABSTRACT FROM AUTHOR]