Is Less Chemotherapy Detrimental in Adults with Philadelphia Chromosome (Ph)-Positive Acute Lymphoblastic Leukemia (ALL) Treated with High-Dose Imatinib? Results of the Prospective Randomized Graaph-2005 Study

Aim: To compare a less intensive regimen based on high-dose imatinib (IM) to an intensive IM/HyperCVAD regimen in adults with Ph+ ALL, in terms of early response and outcome after stem cell transplantation (SCT). Methods: Patients aged 18-60 years with previously untreated Ph+ ALL not evolving from chronic myeloid leukemia were eligible if no contra-indication to chemotherapy and SCT (ClinicalTrials.gov ID, NCT00327678). After a steroid prephase allowing Ph and/or BCR-ABL diagnosis, cycle 1 differed between randomization arms. In arm A (IM-based), IM was given at 800 mg on day 1-28, combined with vincristine (2 mg, day 1, 8, 15, 22) and dexamethasone (40 mg, day 1-2, 8-9, 15-16, and 22-23) only. In arm B (IM/HyperCVAD), IM was given at 800 mg on day 1-14, combined with adriamycin (50 mg/m2, day 4), cyclophosphamide (300 mg/m2/12h, day 1, 2, 3), vincristine (2 mg, day 4 and 11), and dexamethasone (40 mg, day 1-4 and 11-14). All patients received a cycle 2 combining high-dose methotrexate (1 g/m2, day 1) and AraC (3 g/m2/12h, day 2 and 3) with IM at 800 mg on day 1-14, whatever their response. Four intrathecal infusions were given during this induction/consolidation period. Minimal residual disease (MRD) was centrally evaluated by quantitative RQ-PCR after cycle 1 (MRD1) and cycle 2 (MRD2). Major MRD response was defined as BCR-ABL/ABL ratio <0.1%. Then, all patients were to receive allogeneic SCT using related or unrelated matched donor stem cells or autologous SCT if no donor and a major MRD2 response. IM/chemotherapy maintenance was planned after autologous SCT. In the absence of SCT, patients received alternating cycles 1 (as in arm B) and cycles 2 followed by maintenance, like in the published IM/HyperCVAD regimen. The primary objective was non-inferiority of arm A in term of major MRD2 response. Secondary objectives were CR rate, SCT rate, treatment- and transplant-related mortality, relapse-free (RFS), event-free (EFS) and overall (OS) survival. Results: Among the 270 patients randomized between May 2006 and August 2011, 265 patients were evaluable for this analysis (133 arm A, 132 arm B; median age, 47 years; median follow-up, 40 months). Main patient characteristics were well-balanced between both arms. Due to higher induction mortality in arm B (9 versus 1 deaths; P=0.01), CR rate was higher in the less intensive arm A (98% versus 89% after cycle 1 and 98% versus 91% after cycle 2; P= 0.003 and 0.006, respectively). A total of 213 and 205 patients were evaluated for bone marrow MRD1 and MRD2. The rates of patients reaching major MRD response and undetectable MRD were 45% (44% arm A, 46% arm B; P=0.79) and 10% (in both arms) at MRD1 and 66% (68% arm A, 63.5% arm B; P=0.56) and 25% (28% arm A, 22% arm B; P=0.33) at MRD2, respectively. The non-inferiority primary endpoint was thus demonstrated (P= 0.002). Overall, EFS was estimated at 42% (95% CI, 35-49) and OS at 51% (95% CI, 44-57) at 3 years, with no difference between arm A and B (46% versus 38% and 53% versus 49%; P=0.25 and 0.61, respectively). Of the 251 CR patients, 157 (80 arm A, 77 arm B) and 34 (17 in both arms) received allogeneic and autologous SCT in first CR, respectively. Allogeneic transplant-related mortality was similar in both arms (31.5% versus 22% at 3 years; P=0.51). Of the 157 allografted patients, 133 had MRD2 evaluation and 89 had MRD2 <0.1%. In these patients, MRD2 did not significantly influence post-transplant RFS and OS, either when tested with the 0.1% cutoff or as a continuous log covariate. Of the 34 autografted patients, 31 had MRD2 evaluation and, according to the protocol, 28 had MRD2 <0.1%. When restricting the comparison to patients achieving major MRD2 response and with the current follow-up, a trend for better results was observed after autologous as compared to allogeneic SCT (RFS, 63% versus 49.5% and OS, 69% versus 58% at 3 years; P=0.35 and P=0.08, respectively). Conclusions: In adults, the use of TK inhibitors (TKI) has markedly improved the results of Ph+ ALL therapy, now close to those observed in Ph-negative ALL. We demonstrated here that chemotherapy intensity may be safely reduced when associated with high-dose IM. We will further explore this TKI-based strategy using nilotinib prior to SCT in our next GRAAPH-2013 trial. The trend towards a better outcome after autologous compared to allogeneic SCT observed in MRD responders validates MRD as an important early surrogate endpoint for treatment stratification and new drug investigation in this disease.

Towards a database on societal impact of Mediterranean floods in the framework of the HYMEX project

The NW Mediterranean region experiences every year heavy rainfall and flash floods that occasionally produce catastrophic damages. Less frequent are floods that affect large regions. Although a large number of databases devoted exclusively to floods or considering all kind of natural hazards do exist, usually they only record catastrophic flood events. This paper deals with the new flood database that is being developed within the framework of HYMEX project. Results are focused on four regions representative of the NW sector of Mediterranean Europe: Catalonia, Spain; the Balearic Islands, Spain; Calabria, Italy; and Languedoc-Roussillon, Midi-Pyrenées and PACA, France. The common available 30-yr period starts in 1981 and ends in 2010. The paper shows the database structure and criteria, the comparison with other flood databases, some statistics on spatial and temporal distribution, and an identification of the most important events. The paper also provides a table that includes the date and affected region of all the catastrophic events identified in the regions of study, in order to make this information available for all audiences.

Aproximació al moviment "open access"

[eng] The article describes the background and current state of the open access (OA) movement. Its objectives --with roots in scientists' traditional desire to disseminate their works, in librarians' concerns about the serials crisis, and in technological advances-- were formally articulated in the Budapest Open Access Initiative (BOAI) declaration of 2002. This statement established two strategies for providing access to scientific information without any economic, technical, or legal obstacles: 1) publication of articles in OA journals or 2) deposit by authors of their works in stable institutional or subject-based repositories. The article suggests that this second "route" appears to offer greater possibilities of attaining open access in the short term. However, there still is a lot of work to be done in disseminating the concepts of OA and in training authors regarding procedures for depositing their works: in other words what is needed is a series of promotional activities for overcoming one of today's greatest challenges: author inertia.

Las mineralizaciones filonianas del sector de l'Argentera (Cadenas Costeras Catalanas): Contexto geológico, estructura, tipología y condiciones de formación

Las mineralizaciones filonianas del area de L'Argentera estan encajadas indistintamente en la srie sedimentaria pre-carbonfera y carbonfera y en las granodioritas tardihercinicas. NE-SW y presentan dos asociaciones minerales geograficamente bien discriminadas: de Ba-(F) y de cuarzo + galena + arseniuros de Ni-Co. La serie detrtica roja discordante del Triasico inferior (Buntsandstein) muestra asimismo cemento de baritina (fluorita) o cuarzo, en neta correspondencia con las asociaciones minerales de los filones infrayacentes encajados en el zcalo hercnico. Gran parte del contenido filoniano se deposit a partir de soluciones altarnente salinas (20% NaCl peso eq.) y de bajas temperaturas (90 a 120C). Las observaciones realizadas son compatibles con un modelo deposicional basado en una mezcla de aguas termales ascendentes en fracturas permeables y soluciones sulfatadas percolantes a partir de un ambiente de tipo sabkha instalado en el Buntsandstein superior.

Organic sulfur oxidation to sulfate in soil samples for total sulfur determination by turbidimetry

Sulfur in the soil occurs in two basic forms, organic and inorganic S. The organic form accounts for 95 % of S in most soils. The effectiveness of organic S to oxidate to sulfate was evaluated for total S determination in soil samples by wet (acid) and dry-ash (alkaline) oxidation methods. To evaluate the wet method and the possible use as a reference when evaluating the dry method proposed here, a reference standard from the US National Institute of Standards and Technology (NIST) was used (Montana Soil - NIST 2710). The dry-ash oxidation process with alkaline oxidizing agents is one of the simplest oxidation methods of organic S to the sulfate form and was compared with the wet process. The objective of the study was to develop a dry method that would be easy to apply and allow the complete conversion of organic S to sulfate in soil samples and later detection by turbidimetry. The effectiveness of organic S oxidation to sulfate was evaluated by means of three alkaline oxidation mixtures: NaHCO3 + Ag2O, Eschka mixture (17 % Na2CO3, 66 % MgO, and 17 % K2CO3), and NaHCO3 + CuO. The procedure to quantify the sulfate concentration was based on the reaction with barium chloride and turbidimetric detection. Sulfur quantification in the standard sample by the wet method proved adequate, precise and accurate. It should also be pointed out that no significant differences were found (95 % reliability) between the wet and dry processes (NaHCO3 and Ag2O oxidation mixture) in six different Brazilian soils. The proposed dry method can therefore be used in the preparation of soil samples for total S determination.

Effects of prior hydrogenation on the structure and properties of thermally nanocrystallized silicon layers

Nanocrystalline silicon layers have been obtained by thermal annealing of films sputtered in various hydrogen partial pressures. The as-deposited and crystallized films were investigated by infrared, Raman, x-ray diffraction, electron microscopy, and optical absorption techniques. The obtained data show evidence of a close correlation between the microstructure and properties of the processed material, and the hydrogen content in the as-grown deposit. The minimum stress deduced from Raman was found to correspond to the widest band gap and to a maximum hydrogen content in the basic unannealed sample. Such a structure relaxation seems to originate from the so-called "chemical annealing" thought to be due to Si-H2 species, as identified by infrared spectroscopy. The variation of the band gap has been interpreted in terms of the changes in the band tails associated with the disorder which would be induced by stress. Finally, the layers originally deposited with the highest hydrogen pressure show a lowest stress-which does not correlate with the hydrogen content and the optical band gap¿and some texturing. These features are likely related to the presence in these layers of a significant crystalline fraction already before annealing.

Geochronological constraints on post-extinction recovery of the ammonoids and carbon cycle perturbations during the Early Jurassic

This paper presents the first quantitative study of the Early Jurassic recovery of ammonoids after the end-Triassic mass extinction based on detailed U-Pb ID-TIMS (isotope dilution thermal ionization mass spectrometry) geochronology from ash bed zircons placed within a clear phylogenetical and biochronological framework at the subzonal and species level. This study was triggered by the discovery of a rich Peruvian succession of ammonites, deposited concomitantly with an unusually large number of ash beds. Two major phases of rediversification are observed during the Psiloceras spelae and Angulaticeras zones that correspond to positive peaks in the delta C-13(org) curve, providing a possible link between biodiversity and the global carbon cycle. In the case of the post-extinction recovery, the development of the earliest Hettangian ammonites occurs within the genus Psiloceras, which begins with the occurrence of P. spelae and then explodes into worldwide development of smooth psiloceratids of the Psiloceras planorbis group s.l. This rapid biodiversification likely occurred less than 100 ka after the end-Triassic crisis; the genus Psiloceras occupied all the possible ecological niches worldwide, from the Pacific deep waters to the NW European shallow deposits and also in some rare Tethyan occurrences like at Germig in Tibet. This global dispersion allowed the differentiation of the group in several major phyla, the Schlotheimiidae, Discamphiceratinae, Arietitidae and Lytocerataceae, which were the roots of all other Jurassic and Cretaceous ammonites. (C) 2012 Elsevier B.V. All rights reserved.

Precise U-Pb age constraints for end-Triassic mass extinction, its correlation to volcanism and Hettangian post-extinction recovery

New precise zircon U-Pb ages are proposed for the Triassic-Jurassic (Rhetian-Hettangian) and the Hettangian-Sinemurian boundaries, The ages were obtained by ID-TIMS dating of single chemical-abraded zircons from volcanic ash layers within the Pucara Group, Aramachay Formation in the Utcubamba valley, northern Peru. Ash layers situated between last and first occurrences of boundary-defining ammonites yielded Pb-206/U-238 ages of 201.58 +/- 0.17/0.28 Ma (95% c.l., uncertainties without/with decay constant errors, respectively) for the Triassic-Jurassic and of 199.53 +/- 0.19/0.29 Ma for the Hettangian-Sinemurian boundaries. The former is established on a tuff located 1 m above the last local occurrence of the topmost Triassic genus Choristoceras, and 5 m below the Hettangian genus Psiloceras. The latter sample was obtained from a tuff collected within the Badouxia canadensis beds. Our new ages document total duration of the Hettagian of no more than c. 2 m.y., which has fundamental implications for the interpretation and significance of the ammonite recovery after the topmost Triassic extinction. The U-Pb age is about 0.8 +/- 0.5% older than Ar-40-Ar-39 dates determined on flood basalts of the Central Atlantic Magmatic Province (CAMP). Given the widely accepted hypothesis that inaccuracies in the K-40 decay constants or physical constants create a similar bias between the two dating methods, our new U-Pb zircon age determination for the T/J boundary corroborates the hypothesis that the CAMP was emplaced at the same time and may be responsible for a major climatic turnover and mass extinction. The zircon Pb-206/U-238 age for the T/J boundary is marginally older than the North Mountain Basalt (Newark Supergroup, Nova Scotia, Canada), which has been dated at 201.27 +/- 0.06 Ma [Schoene et al., 2006. Geochim. Cosmochim. Acta 70, 426-445]. It will be important to look for older eruptions of the CAMP and date them precisely by U-Pb techniques while addressing all sources of systematic uncertainty to further test the hypothesis of volcanic induced climate change leading to extinction. Such high-precision, high-accuracy data will be instrumental for constraining the contemporaneity of geological events at a 100 kyr level. (C) 2007 Elsevier B.V. All rights reserved.

De la mano de Keynes: "A tract on monetary reform"

En Tract on Monetary Reform, John Maynard Keynes propuso utilizar la base monetaria y el coeficiente de reserva bancaria como variables instrumentales d¿una política monetaria que había sido considerada hasta entonces innecesaria. En este trabajo se intenta desvelar las primeras contribuciones de Keynes al progreso del análisis económico

Orchid growth and nutrition in response to mineral and organic fertilizers

Orchid fertilization is fundamental for a satisfactory plant growth and development for commercial orchid production as well as in collections. Mineral and/or organic sources can be used for fertilization. The objective of this study was to evaluate the effect of the use of organic and/or mineral fertilizers on the nutrition and growth of orchid (Laelia purpurata 'werkhanserii' x L. lobata 'Jeni') seedlings in greenhouse. The following fertilizers were tested: an NPK fertilizer + micronutrients; a Ca source in the form of calcium nitrate; two organic fertilizers, one prepared with a mixture of bone meal, castor meal and ash, and a similar commercial fertilizer. The organic fertilizers were distributed on the surface of the pots every two months and the minerals were applied weekly to the substrate in 25 mL aliquots of a solution containing 1 g L-1 of the respective fertilizer. The plant response to the application of mineral together with organic fertilizer was better, with higher dry matter production than by the isolated application of each fertilizer (organic or mineral). The treatments with calcium nitrate + NPK fertilizer did not differ significantly from the use of NPK fertilizer, probably due to the S deficiency detected in a mineral analysis of the tissues. Commercial organic fertilizer had a very elevated B level, leading to toxicity symptoms, reduced growth and necrotized tips of the older leaves in all fertilized treatments.

Unusual concentration of Early Albian arthropod-bearing amber in the Basque-Cantabrian Basin (El Soplao, Cantabria, Spain): Palaeoenvironmental and paleobiological implications.

The El Soplao site is a recently-discovered Early Albian locality of the Basque-Cantabrian Basin (northern Spain) that has yielded a number of amber pieces with abundant bioinclusions. The amber-bearing deposit occurs in a non-marine to transitional marine siliciclastic unit (Las Peñosas Formation) that is interleaved within a regressive-transgressive, carbonate-dominated Lower Aptian-Upper Albian marine sequence. The Las Peñosas Formation corresponds to the regressive stage of this sequence and in its turn it splits into two smaller regressive-transgressive cycles. The coal and amber-bearing deposits occur in deltaic-estuarine environments developed during the maximum regressive episodes of these smaller regressive-transgressive cycles. The El Soplao amber shows Fourier Transform Infrared Spectroscopy spectra similar to other Spanish Cretaceous ambers and it is characterized by the profusion of sub-aerial, stalactite-like flows. Well-preserved plant cuticles assigned to the conifer genera Frenelopsis and Mirovia are abundant in the beds associated with amber. Leaves of the ginkgoalean genera Nehvizdya and Pseudotorellia also occur occasionally. Bioinclusions mainly consist of fossil insects of the orders Blattaria, Hemiptera, Thysanoptera, Raphidioptera, Neuroptera, Coleoptera, Hymenoptera and Diptera, although some spiders and spider webs have been observed as well. Some insects belong to groups scarce in the fossil record, such as a new morphotype of the wasp Archaeromma (of the family Mymarommatidae) and the biting midge Lebanoculicoides (of the monogeneric subfamily Lebanoculicoidinae). This new amber locality constitutes a very significant finding that will contribute to improving the knowledge and comprehension of the Albian non-marine paleoarthropod fauna.

Pedological and isotopic relations of a highland tropical peatland, Mountain Range of the Espinhaço Meridional (Brazil)

The evolution of organic matter sources in soil is related to climate and vegetation dynamics in the past recorded in paleoenvironmental Quaternary deposits such as peatlands. For this reason, a Histosol of the mineralotrophic peatland from the Pau-de-Fruta Special Protection Area - SPA, Espinhaço Meridional, State of Minas Gerais, was described and characterized to evidence the soil constituent materials and properties as related to changes in environmental conditions, supported by the isotopic and elementary characterization of soil C and N and 14C ages. Samples were collected in a depression at 1,350 m asl, where Histosols are possibly more developed due to the great thickness (505 cm). Nowadays, the area is colonized by vegetation physiognomies of the Cerrado Biome, mainly rocky and wet fields (Campo Rupestre and Campo Úmido), aside from fragments of Semidecidual Seasonal Forest, called Capões forests. The results this study showed that early the genesis of the analyzed soil profile showed a high initial contribution of mostly herbaceous organic matter before 8,090 ± 30 years BP (14C age). In the lower-mid Holocene, between 8,090 ± 30 years AP (14C age) to ± 4,100 years BP (interpolated age), the vegetation gradually became more woody, with forest expansion, possibly due to increased humidity, suggesting the existence of a more woody Cerrado in the past than at present. Drier climate conditions than the current were concluded ± 2,500 years BP (interpolated age) and that after 430 years BP (14C age) the forest gave way to grassland, predominantly. After the dry season, humidity increased to the current conditions. Due to these climate fluctuations during the Holocene, three decomposition stages of organic matter were observed in the Histosols of this study, with prevalence of the most advanced (sapric), typical of a deposit in a highly advanced stage of pedogenetic evolution.

Puutuhkasta ja muista jäteaineista valmistetut pelletit rauduskoivun taimien ravinnelähteenä

Summary: Pellets made of wood ash and other wastes as nutrient sources for silver birch seedlings

Neotropical woodlice (isopoda) colonizing leaf-litter of pioneer plants in a coal residue disposal environment

The irregular disposal of coal combustion residues has adverse impacts on terrestrial ecosystems. Pioneer plants and soil invertebrates play an important role in the recovery of these areas. The goal of this study was to investigate the colonization patterns of terrestrial isopods (Oniscidea) in leaf litter of three spontaneous pioneer plants (grass - Poaceae, shrub - Euphorbiaceae, tree - Anarcadiaceae) at sites used for fly ash or boiler slag disposal. The experiment consisted of eight blocks (four per disposal site) of 12 litter bags each (four per plant species) that were randomly removed after 6, 35, 70 or 140 days of field exposure. Three isopod species were found in the litter bags: Atlantoscia floridana (van Name, 1940) (Philosciidae; n = 116), Benthana taeniata Araujo & Buckup, 1994 (Philosciidae; n = 817) and Balloniscus sellowii (Brandt, 1833) (Balloniscidae; n = 48). The isopods colonized the three leaf-litter species equally during the exposure period. However, the pattern of leaf-litter colonization by these species suggests a conflict of objectives between high quality food and shelter availability. The occurrence of A. floridana and the abundance and fecundity of B. taeniata were influenced by the residue type, indicating that the isopods have different degrees of tolerance to the characteristics of the studied sites. Considering that terrestrial isopods are abundant detritivores and stimulate the humus-forming processes, it is suggested that they could have an indirect influence on the soil restoration of this area.

Early Iron Age Pottery: A Quantitative Approach, Proceedings of the International Round Table organized by the Swiss School of Archaeology in Greece (Athens, November 28-30, 2008)

Quantitative approaches in ceramology are gaining ground in excavation reports, archaeological publications and thematic studies. Hence, a wide variety of methods are being used depending on the researchers' theoretical premise, the type of material which is examined, the context of discovery and the questions that are addressed. The round table that took place in Athens on November 2008 was intended to offer the participants the opportunity to present a selection of case studies on the basis of which methodological approaches were discussed. The aim was to define a set of guidelines for quantification that would prove to be of use to all researchers. Contents: 1) Introduction (Samuel Verdan); 2) Isthmia and beyond. How can quantification help the analysis of EIA sanctuary deposits? (Catherine Morgan); 3) Approaching aspects of cult practice and ethnicity in Early Iron Age Ephesos using quantitative analysis of a Protogeometric deposit from the Artemision (Michael Kerschner); 4) Development of a ceramic cultic assemblage: Analyzing pottery from Late Helladic IIIC through Late Geometric Kalapodi (Ivonne Kaiser, Laura-Concetta Rizzotto, Sara Strack); 5) 'Erfahrungsbericht' of application of different quantitative methods at Kalapodi (Sara Strack); 6) The Early Iron Age sanctuary at Olympia: counting sherds from the Pelopion excavations (1987-1996) (Birgitta Eder); 7) L'aire du pilier des Rhodiens à Delphes: Essai de quantification du mobilier (Jean-Marc Luce); 8) A new approach in ceramic statistical analyses: Pit 13 on Xeropolis at Lefkandi (David A. Mitchell, Irene S. Lemos); 9) Households and workshops at Early Iron Age Oropos: A quantitative approach of the fine, wheel-made pottery (Vicky Vlachou); 10) Counting sherds at Sindos: Pottery consumption and construction of identities in the Iron Age (Stefanos Gimatzidis); 11) Analyse quantitative du mobilier céramique des fouilles de Xombourgo à Ténos et le cas des supports de caisson (Jean-Sébastien Gros); 12) Defining a typology of pottery from Gortyn: The material from a pottery workshop pit, (Emanuela Santaniello); 13) Quantification of ceramics from Early Iron Age tombs (Antonis Kotsonas); 14) Quantitative analysis of the pottery from the Early Iron Age necropolis of Tsikalario on Naxos (Xenia Charalambidou); 15) Finding the Early Iron Age in field survey: Two case studies from Boeotia and Magnesia (Vladimir Stissi); 16) Pottery quantification: Some guidelines (Samuel Verdan)