New methodology for assessing the environmental burden of cement mortars with partial replacement of coal bottom ash and fly ash.

This paper assess the mechanical an environmental behaviour of cement mortars manufactured with addition of fly ash (FA) and bottom ash (BA), as partial cement replacement (10%, 25% and 35%). The environmental behaviour was studied by leaching tests, which were performed under several temperature (23 °C and 60 °C) and pH (5 and 10) conditions, and ages (1, 2, 4 and 7 days). Then, the accumulated amount of the different constituents leached was analysed. In order to obtain an environmental burden (EB) value of each cement mixture, a new methodology was developed. The EB value obtained is related to the amount leached and the hazardous level of each constituent. Finally, the integral study of compressive strength and EB values of cement mixtures allowed their classification. The results showed that mortars manufactured with ordinary Portland cement (OPC) and with coal BA had similar or even better environmental and mechanical behaviour than mortars with FA. Therefore, the partial replacement of cement by BA might be as suitable or even better as the replacement by FA.

The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression.

Smoldering multiple myeloma (SMM) precedes multiple myeloma (MM). The risk of progression of SMM patients is not uniform, thus different progression-risk models have been developed, although they are mainly based on clinical parameters. Recently, genomic predictors of progression have been defined for untreated SMM. However, the usefulness of such markers in the context of clinical trials evaluating upfront treatment in high-risk SMM (HR SMM) has not been explored yet, precluding the identification of baseline genomic alterations leading to drug resistance. For this reason, we carried out next-generation sequencing and fluorescent in-situ hybridization studies on 57 HR and ultra-high risk (UHR) SMM patients treated in the phase II GEM-CESAR clinical trial (NCT02415413). DIS3, FAM46C, and FGFR3 mutations, as well as t(4;14) and 1q alterations, were enriched in HR SMM. TRAF3 mutations were specifically associated with UHR SMM but identified cases with improved outcomes. Importantly, novel potential predictors of treatment resistance were identified: NRAS mutations and the co-occurrence of t(4;14) plus FGFR3 mutations were associated with an increased risk of biological progression. In conclusion, we have carried out for the first time a molecular characterization of HR SMM patients treated with an intensive regimen, identifying genomic predictors of poor outcomes in this setting.

Burning fire-prone Mediterranean shrublands: immediate changes in soil microbial community structure and ecosystem functions.

Wildfires subject soil microbes to extreme temperatures and modify their physical and chemical habitat. This might immediately alter their community structure and ecosystem functions. We burned a fire-prone shrubland under controlled conditions to investigate (1) the fire-induced changes in the community structure of soil archaea, bacteria and fungi by analysing 16S or 18S rRNA gene amplicons separated through denaturing gradient gel electrophoresis; (2) the physical and chemical variables determining the immediate shifts in the microbial community structure; and (3) the microbial drivers of the change in ecosystem functions related to biogeochemical cycling. Prokaryotes and eukaryotes were structured by the local environment in pre-fire soils. Fire caused a significant shift in the microbial community structure, biomass C, respiration and soil hydrolases. One-day changes in bacterial and fungal community structure correlated to the rise in total organic C and NO(3)(-)-N caused by the combustion of plant residues. In the following week, bacterial communities shifted further forced by desiccation and increasing concentrations of macronutrients. Shifts in archaeal community structure were unrelated to any of the 18 environmental variables measured. Fire-induced changes in the community structure of bacteria, rather than archaea or fungi, were correlated to the enhanced microbial biomass, CO(2) production and hydrolysis of C and P organics. This is the first report on the combined effects of fire on the three biological domains in soils. We concluded that immediately after fire the biogeochemical cycling in Mediterranean shrublands becomes less conservative through the increased microbial biomass, activity and changes in the bacterial community structure.

Characterization of the public transit air microbiome and resistome reveals geographical specificity.

BACKGROUND: The public transit is a built environment with high occupant density across the globe, and identifying factors shaping public transit air microbiomes will help design strategies to minimize the transmission of pathogens. However, the majority of microbiome works dedicated to the public transit air are limited to amplicon sequencing, and our knowledge regarding the functional potentials and the repertoire of resistance genes (i.e. resistome) is limited. Furthermore, current air microbiome investigations on public transit systems are focused on single cities, and a multi-city assessment of the public transit air microbiome will allow a greater understanding of whether and how broad environmental, building, and anthropogenic factors shape the public transit air microbiome in an international scale. Therefore, in this study, the public transit air microbiomes and resistomes of six cities across three continents (Denver, Hong Kong, London, New York City, Oslo, Stockholm) were characterized. RESULTS: City was the sole factor associated with public transit air microbiome differences, with diverse taxa identified as drivers for geography-associated functional potentials, concomitant with geographical differences in species- and strain-level inferred growth profiles. Related bacterial strains differed among cities in genes encoding resistance, transposase, and other functions. Sourcetracking estimated that human skin, soil, and wastewater were major presumptive resistome sources of public transit air, and adjacent public transit surfaces may also be considered presumptive sources. Large proportions of detected resistance genes were co-located with mobile genetic elements including plasmids. Biosynthetic gene clusters and city-unique coding sequences were found in the metagenome-assembled genomes. CONCLUSIONS: Overall, geographical specificity transcends multiple aspects of the public transit air microbiome, and future efforts on a global scale are warranted to increase our understanding of factors shaping the microbiome of this unique built environment.

External photon radiation treatment for prostate cancer: Uncomplicated and cancer-free control probability assessment of 36 plans.

PURPOSE: To perform a systematic and thorough assessment, using the Uncomplicated and Cancer-Free Control Probability (UCFCP) function, of a broad range of photon prostate cancer RT treatments, on the same scenario (a unique pelvic CT set). UCFCP considers, together with the probabilities of local tumour control (TCP) and deterministic (late) sequelae (NTCP), the second primary cancer risk (SPCR) due to photon and neutron peripheral doses. METHODS AND MATERIALS: Thirty-six radiotherapy plans were produced for the same CT. 6, 10, 15 and 18 MV 3DCRT, IMRT and VMAT (77.4 Gy in 43 fractions) and 6 and 10 MV SBRT (36.25 Gy in 5 fractions with flattened and FFF beams) for Elekta, Siemens and Varian Linacs plans were included. DVH and peripheral organ dosimetry were used to compute TCP, NTCP, and SPCR (the competition and LNT models) for further plan ranking. RESULTS: Biological models (and parameters) used predicted an outcome which is in agreement with epidemiological findings. SBRT plans showed the lowest SPCR and a below average NTCPrectal. High energy plans did not rank worse than the low energy ones. Intensity modulated plans were ranked above the 3D conformal techniques. CONCLUSIONS: According to UCFCP, the best plans were the10 MV SBRTs. SPCR rates were low and did not show a substantial impact on plan ranking. High energy intensity-modulated plans did not increase in excess the average of SPCR. Even more, they ranked among the best, provided that MU were efficiently managed.

10-MV SBRT FFF IRRADIATION TECHNIQUE IS ASSOCIATED TO THE LOWEST PERIPHERAL DOSE: THE OUTCOME OF 142 TREATMENT PLANS FOR THE 10 MOST COMMON TUMOUR LOCATIONS.

There is a growing interest in the combined use of Stereotactic Body Radiation Therapy (SBRT) with Flattening Filter Free (FFF) due to the high local control rates and reduced treatment times, compared to conventionally fractionated treatments. It has been suggested that they may also provide a better radiation protection to radiotherapy patients as a consequence of the expected decrease in peripheral doses. This work aims to determine this reduction in unattended out-of-field regions, where no CT information is available but an important percentage of second primary cancers occur. For that purpose, ten different cases suitable for SBRT were chosen. Thus, 142 different treatment plans including SBRT, as well as 3D-CRT, IMRT and VMAT (with standard fractionation) in low and high energies for Varian (FF and FFF), Siemens and Elekta machines were created. Then, photon and neutron peripheral dose in 14 organs were assessed and compared using two analytical models. For the prostate case, uncomplicated and cancer free control probability estimation was also carried out. As a general behavior, SBRT plans led to the lowest peripheral doses followed by 3D-CRT, VMAT and IMRT, in this order. Unflattened beams proved to be the most effective in reducing peripheral doses, especially for 10 MV. The obtained results suggest that FFF beams for SBRT with 10 MV represent the best compromise between dose delivery efficiency and peripheral dose reduction.

Agricultural use of leachates obtained from two different vermicomposting processes.

The objective of this paper was to investigate the possible agricultural use of the vermicomposting process leachates. Two leachates coming, respectively, from the vermicomposting of cow dung (SCD) and the vermicomposting of green forages (SGF), as well as solution of Hewitt (C) were used at a dose of 1 ml 500 ml(-1) in the foliar fertilization of tomato plants. Treatments were applied 30, 60 and 90 days after planting (DAP). The obtained results showed that foliar fertilization with SCD and SGF increased the morphological and chemical parameters on tomato crop with respect to the plants receiving foliar treatment with SH and C, possibly due to the humic substances content in SCD and SGF. The higher content of humic substances in SGF with respect to the SCD are possibly the responsible of the higher chlorophyll contents observed in the plants receiving the former treatment. This aspect possibly promoted an increase in plant photosynthesis and therefore an increase in fruit quality.

Application of different organic amendments in a gasoline contaminated soil: effect on soil microbial properties.

The effects of four organic wastes, including cotton gin crushed compost (CC), poultry manure (PM), sewage sludge (SS) and organic municipal solid waste (MSW) on some biological properties of a Xerollic Calciorthid soil polluted with gasoline at two loading rates (5% and 10%) were studied in an incubation experiment. Three hundred grams of sieved soil (<2mm) were polluted with gasoline and mixed with PM at a rate of 10%, CC at a rate of 17.2%, SS at a rate of 23.1%, or MSW at a rate of 13.1%, applying to the soil the same amount of organic matter with each organic amendment. An unamended soil, non polluted (C) and polluted with gasoline at 5% (G1) and 10% (G2) rate were used as reference. Soil samples were collected after 1, 30, 60, 90, 120, 180 and 270 d of incubation and analyzed for microbial biomass carbon, respiration and dehydrogenase, urease, beta-glucosidase, phosphatase and arylsulfatase activities. At the end of the incubation period, soil biological properties were higher in organic amended soils than in C, G1 and G2 treatments. In particular, soil microbial biomass carbon and dehydrogenase, urease, beta-glucosidase, phosphatase and arylsulfatase activities increased 87.1%, 92.9%, 88.7%, 93.2%, 78.2% and 85.3%, respectively for CC-amended soils respect to G2, 85.7%, 82.3%, 87.3%, 92.2%, 76.7% and 83.6%, respectively for PM-amended soils; 82%, 90%, 84.8%, 89.9%, 74.1% and 80%, respectively for SS-amended soils; and 71.3%, 78.3% 26.2%, 38.2%, 79.7% and 88.6%, respectively for MSW-amended soils. Since the adsorption capacity of gasoline was higher in CC than the PM, SS and MSW-amended soils, it can be concluded that the addition of organic wastes with higher humic acid concentration is more beneficial for remediation of soils polluted with gasoline.

Prognostic value of antigen expression in multiple myeloma: a PETHEMA/GEM study on 1265 patients enrolled in four consecutive clinical trials.

Persistence of minimal residual disease (MRD) after treatment for myeloma predicts inferior outcomes, but within MRD-positive patients there is great heterogeneity with both early and very late relapses. Among different MRD techniques, flow cytometry provides additional information about antigen expression on tumor cells, which could potentially contribute to stratify MRD-positive patients. We investigated the prognostic value of those antigens required to monitor MRD in 1265 newly diagnosed patients enrolled in the GEM2000, GEM2005MENOS65, GEM2005MAS65 and GEM2010MAS65 protocols. Overall, CD19pos, CD27neg, CD38lo, CD45pos, CD81pos, CD117neg and CD138lo expression predicted inferior outcomes. Through principal component analysis, we found that simultaneous CD38lowCD81posCD117neg expression emerged as the most powerful combination with independent prognostic value for progression-free survival (HR:1.69; P=0.002). This unique phenotypic profile retained prognostic value among MRD-positive patients. We then used next-generation flow to determine antigen stability throughout the course of the disease, and found that the expression of antigens required to monitor MRD is mostly stable from diagnosis to MRD stages, except for CD81 whose expression progressively increased from baseline to chemoresistant tumor cells (14 vs 28%). Altogether, we showed that the phenotypic profile of tumor cells provides additional prognostic information, and could be used to further predict risk of relapse among MRD-positive patients.

Application of two organic wastes in a soil polluted by lead: effects on the soil enzymatic activities.

The effects of adding a crushed cotton gin compost (CCGC) and a poultry manure (PM) on the enzymatic activities of a Typic Xerofluvent soil polluted with Pb were studied in the laboratory. Three hundred grams of sieved soil (<2 mm) were mixed with PM at a rate of 10% or CCGC at a rate of 17.2%, applying to the soil the same amount of organic matter with each organic amendment. Urease, protease-BBA, beta-glucosidase, alkaline phosphatase, and arylsulfatase activities were measured at four different incubation times (1, 7, 15, and 45 d) in soils containing seven concentrations (100, 250, 500, 1000, 2500, 5000, and 8000 mg kg-1) of Pb, and in the same soils amended with CCGC and PM. In all treatments and incubation times, the inhibition percentage of soil enzyme activities by Pb was lower in soils amended with the PM and CCGC than in nonamended soils, and it differed with the organic amendment. In this respect, the in the 8000 mg Pb kg-1 treatment at the end of the incubation period, the protease-BBA activity inhibition percentage was lower (14.7 and 33.9% lower, respectively) in CCGC- than in PM-amended soils. Since the adsorption capacity of Pb was higher in CCGC- than the PM-amended soils, the addition of organic wastes with higher humic acid concentration is more beneficial for remediation of soils polluted with Pb.

Factores predictores de respuesta completa patológica tras inducción (ypT0N0M0) en cáncer de pulmón no microcítico y resultados a corto plazo: resultados del Grupo Español de Cirugía Torácica Videoasistida (GE-VATS) / Predictive factors of pathological complete response after induction (ypT0N0M0) in non-small cell lung cancer and short-term outcomes: results of the Spanish Group of Video-assisted Thoracic Surgery (GE-VATS)

Introducción Analizar los factores predictores de respuesta patológica completa (RCp) en pacientes con cáncer de pulmón no microcítico (CPNM) sometidos a resección pulmonar anatómica tras terapia de inducción y evaluar los resultados postoperatorios de estos pacientes. Métodos Se incluyeron en el estudio todos los pacientes registrados de forma prospectiva en la base de datos del grupo de trabajo GE-VATS reclutados entre el 20 de diciembre de 2106 y el 20 de marzo de 2018, sometidos a resección pulmonar anatómica por CPNM tras tratamiento de inducción. La población se dividió en dos grupos: pacientes que obtuvieron respuesta completa patológica tras inducción (RCp) y pacientes que no obtuvieron una respuesta patológica completa tras inducción (no-RCp). Se realizó un análisis multivariante mediante una regresión logística binaria para determinar los factores predictores de RCp y se analizaron los resultados postoperatorios de los pacientes. Resultados De los 241 pacientes analizados, 36 pacientes (14,9%) alcanzaron RCp. Los factores predictores de RCp fueron el sexo masculino (OR 2,814, IC 95% 1,015-7,806), la histología de carcinoma escamoso (OR 3,065, IC 95% 1,233-7,619) u otra distinta de adenocarcinoma (ADC) (OR 5788, IC 95% 1,878-17,733), la terapia de inducción que incluye radioterapia (OR 4,096, IC 95% 1,785-9,401) y terapias dirigidas (OR 7,625, IC 95% 2,147-27,077). La ocurrencia de complicaciones respiratorias postoperatorias fue superior en los pacientes que recibieron quimio-radioterapia de inducción (p = 0,032). Conclusiones El sexo masculino, la histología de carcinoma escamoso o diferente de ADC y la terapia de inducción que incluye radioterapia o terapia dirigida son factores predictores positivos para la obtención de RCp. La quimio-radioterapia de inducción se asocia con un mayor riesgo de complicaciones respiratorias postoperatorias (AU)

Introduction To analyze the predictors of pathological complete response (pCR) in not small cells lung carcinoma (NSCLC) patients who underwent anatomical lung resection after induction therapy and to evaluate the postoperative results of these patients. Methods All patients prospectively registered in the database of the GE-VATS working group undergone anatomic lung resection by NSCLC after induction treatment and recruited between December 20th 2016, and March 20th 2018, were included in the study. The population was divided into two groups: patients who obtained a complete pathological response after induction (pCR) and patients who did not obtain a complete pathological response after induction (non-pCR). A multivariate analysis was performed using a binary logistic regression to determine the predictors of pCR and the postoperative results of patients were analyzed. Results Of the 241 patients analyzed, 36 patients (14.9%) achieved pCR. Predictive factors for pCR are male sex (OR 2.814, 95% CI 1.015-7.806), histology of squamous carcinoma (OR 3.065, 95% CI 1.233-7.619) or other than adenocarcinoma (ADC) (OR 5.788, 95% CI 1.878-17.733) and induction therapy that includes radiation therapy (OR 4.096, 95% CI 1.785-9.401) and targeted therapies (OR 7.625, 95% CI 2.147-27.077). Prevalence of postoperative pulmonary complications was higher in patients treated with neoadjuvant chemo-radiotherapy (p = 0.032). Conclusions Male sex, histology of squamous carcinoma or other than ADC, and induction therapy that includes radiotherapy or targeted therapy are positive predictors for obtaining pCR. Induction chemo-radiotherapy is associated with a higher risk of postoperative pulmonary complications (AU)

Similar outcomes after newly implemented rats approach compared to standard vats for anatomical lung resection. A propensity-score matched analysis / Resultados similares de un abordaje robótico (RATS) recientemente implementado comparado con un abordaje VATS convencional para resecciones pulmonares anatómicas: análisis de datos emparejados por puntuación de propensión

Introduction Outcomes after the introduction of surgical innovations can be impaired by learning periods. The aim of this study is to compare the short-term outcomes of a recently implemented RATS approach to a standard VATS program for anatomical lung resections. Methods Retrospective review of consecutive patients undergoing pulmonary anatomical resection through a minimally invasive approach since RATS approach was applied in our department (June 01, 2018, to November 30, 2019). Propensity score matching was performed according to patients’ age, gender, ppoFEV1, cardiac comorbidity, type of malignancy, and type of resection. Outcome evaluation includes: overall morbidity, significant complications (cardiac arrhythmia, pneumonia, prolonged air leak, and reoperation), 30-day mortality, and length of hospital stay. Data were compared by two-sided chi-square or Fisher's exact test for categorical and Mann–Whitney U test for continuous variables. Results A total of 273 patients (206 VATS, 67 RATS) were included in the study. After propensity score matching, data of 132 patients were analyzed. The thirty-days mortality was nil. Overall morbidity (RATS: 22.4%, VATS: 29.2%; p=0.369), major complications (RATS: 9% vs VATS: 9.2%; p=0.956) and the rates of specific major complications (cardiac arrhythmia RATS: 4.5%, VATS: 4.6%, p=1; pneumonia RATS:0%, VATS:4.6%, p=0.117; prolonged air leak RATS: 7.5%; VATS: 4.6%, p=0.718) and reoperation (RATS: 3%, VATS: 1.5%, p=1) were comparable between both groups. The median length of stay was 3 days in both groups (p=0.101) (AU)

Introducción La introducción de innovaciones quirúrgicas se asocia con períodos de aprendizaje que pueden afectar a los resultados. El objetivo de este estudio es comparar los resultados postoperatorios de un abordaje RATS para resecciones pulmonares anatómicas implementado recientemente frente a los de un abordaje VATS convencional. Métodos Revisión retrospectiva de los pacientes sometidos a resección pulmonar anatómica mediante un abordaje mínimamente invasivo en nuestro centro desde el inicio del programa de cirugía RATS (junio de 2018) hasta noviembre de 2019. Los pacientes fueron emparejados por puntuación de propensión según variables de riesgo. Los resultados analizados fueron: morbilidad global, complicaciones (mayores, arritmia, neumonía, fuga aérea prolongada y reintervención), mortalidad a los 30 días y estancia hospitalaria. Los datos se compararon mediante la prueba de chi-cuadrado o la exacta de Fisher para variables categóricas y la prueba de U de Mann-Whitney para variables continuas. Resultados Se incluyeron en el estudio 273 pacientes (206 VATS, 67 RATS). Tras el emparejamiento, se analizaron los datos de 132 pacientes. La mortalidad a los 30 días fue nula. La morbilidad global (RATS: 22,4%, VATS: 29,2%; p=0,369), complicaciones mayores (RATS: 9%, VATS: 9,2%; p=0,956), arritmia (RATS: 4,5%, VATS: 4,6%, p=1); neumonía (RATS: 0%, VATS: 4,6%, p=0,117); fuga aérea prolongada (RATS: 7,5%; VATS: 4,6%, p=0,718) y reintervención (RATS: 3%, VATS: 1,5%, p=1) fueron comparables entre ambos grupos. La mediana de la estancia hospitalaria fue de 3 días en ambos grupos (p=0,101). Conclusiones Un programa RATS para resecciones pulmonares anatómicas puede implementarse de manera segura por cirujanos experimentados en VATS sin aumentar los índices de morbilidad (AU)

Bortezomib and thalidomide maintenance after stem cell transplantation for multiple myeloma: a PETHEMA/GEM trial.

The phase III trial GEM05MENOS65 randomized 390 patients 65 years old or younger with newly diagnosed symptomatic multiple myeloma (MM) to receive induction with thalidomide/dexamethasone, bortezomib/thalidomide/dexamethasone and Vincristine, BCNU, melphalan, cyclophosphamide, prednisone/vincristine, BCNU, doxorubicin, dexamethasone bortezomib (VBMCP/VBAD/B) followed by autologous stem cell transplantation (ASCT) with MEL-200. After ASCT, a second randomization was performed to compare thalidomide/bortezomib (TV), thalidomide (T) and alfa-2b interferon (alfa2-IFN). Maintenance treatment consisted of TV (thalidomide 100 mg daily plus one cycle of intravenous bortezomib at 1.3 mg/m2 on days 1, 4, 8 and 11 every 3 months) versus T (100 mg daily) versus alfa2-IFN (3 MU three times per week) for up to 3 years. A total of 271 patients were randomized (TV: 91; T: 88; alfa2-IFN: 92). The complete response (CR) rate with maintenance was improved by 21% with TV, 11% with T and 17% with alfa2-IFN (P, not significant). After a median follow-up of 58.6 months, the progression-free survival (PFS) was significantly longer with TV compared with T and alfa2-IFN (50.6 vs 40.3 vs 32.5 months, P=0.03). Overall survival was not significantly different among the three arms. Grade 2-3 peripheral neuropathy was observed in 48.8%, 34.4% and 1% of patients treated with TV, T and alfa2-IFN, respectively. In conclusion, bortezomib and thalidomide maintenance resulted in a significantly longer PFS when compared with thalidomide or alfa2-IFN. (no. EUDRA 2005-001110-41).

Differentiation stage of myeloma plasma cells: biological and clinical significance.

The notion that plasma cells (PCs) are terminally differentiated has prevented intensive research in multiple myeloma (MM) about their phenotypic plasticity and differentiation. Here, we demonstrated in healthy individuals (n=20) that the CD19-CD81 expression axis identifies three bone marrow (BM)PC subsets with distinct age-prevalence, proliferation, replication-history, immunoglobulin-production, and phenotype, consistent with progressively increased differentiation from CD19+CD81+ into CD19-CD81+ and CD19-CD81- BMPCs. Afterwards, we demonstrated in 225 newly diagnosed MM patients that, comparing to normal BMPC counterparts, 59% had fully differentiated (CD19-CD81-) clones, 38% intermediate-differentiated (CD19-CD81+) and 3% less-differentiated (CD19+CD81+) clones. The latter patients had dismal outcome, and PC differentiation emerged as an independent prognostic marker for progression-free (HR: 1.7; P=0.005) and overall survival (HR: 2.1; P=0.006). Longitudinal comparison of diagnostic vs minimal-residual-disease samples (n=40) unraveled that in 20% of patients, less-differentiated PCs subclones become enriched after therapy-induced pressure. We also revealed that CD81 expression is epigenetically regulated, that less-differentiated clonal PCs retain high expression of genes related to preceding B-cell stages (for example: PAX5), and show distinct mutation profile vs fully differentiated PC clones within individual patients. Together, we shed new light into PC plasticity and demonstrated that MM patients harbouring less-differentiated PCs have dismal survival, which might be related to higher chemoresistant potential plus different molecular and genomic profiles.

Application of two organic amendments on soil restoration: effects on the soil biological properties.

One method for recovering degraded soils in semiarid regions is to add organic matter to improve soil characteristics, thereby enhancing biogeochemical nutrient cycling. In this paper, we studied the changes in soil biological properties as a result of adding a crushed cotton gin compost (CCGC) and a poultry manure (PM) for 4 yr to restore a Xerollic Calciorthid located near Seville (Guadalquivir Valley, Andalusia, Spain). Organic wastes were applied at rates of 5, 7.5, and 10 Mg organic matter ha(-1). One year after the assay began, spontaneous vegetation had appeared in the treated plots, particularly in that receiving a high PM and CCGC dose. After 4 yr, the plant cover in these treated plots was around 88 and 79%, respectively, compared with 5% for the control. The effects on soil microbial biomass and six soil enzymatic activities (dehydrogenase, urease, BBA-protease, beta-glucosidase, arylsulfatase, and alkaline phosphatase activities) were ascertained. Both added organic wastes had a positive effect on the biological properties of the soil, although at the end of the experimental period and at high dosage, soil microbial biomass and soil enzyme activities were generally higher in the PM-amended soils compared to the CCGC-amended soils. Enzyme activity from the PM-amended soil was 5, 15, 13, 19, 22, 30, and 6% greater than CCGC-amended soil for soil microbial biomass, urease, BBA-protease, beta-glucosidase, alkaline phosphatase, arylsulfatase, and dehydrogenase activities, respectively. After 4 yr, the percentage of plant cover was > 48% in all treated plots and 5% in the control.

Rat liver nucleoside diphosphosugar or diphosphoalcohol pyrophosphatases different from nucleotide pyrophosphatase or phosphodiesterase I: substrate specificities of Mg(2+)-and/or Mn(2+)-dependent hydrolases acting on ADP-ribose.

Three rat liver nucleotides(5') diphosphosugar (NDP-sugar) or nucleoside(5') diphosphoalcohol pyrophosphatases are described: two were previously identified in experiments measuring Mg(2+)-dependent ADP-ribose pyrophosphatase activity (Miró et al. (1989) FEBS Lett. 244, 123-126), and the other is a new, Mn(2+)-dependent ADP-ribose pyrophosphatase. They are resolved by ion-exchange chromatography, and differ by their substrate and cation specificities, KM values for ADP-ribose, pH-activity profiles, molecular weights and isoelectric points. The enzymes were tested for activity towards: reducing (ADP-ribose, IDP-ribose) and non-reducing NDP-sugars (ADP-glucose, ADP-mannose, GDP-mannose, UDP-mannose, UDP-glucose, UDP-xylose, CDP-glucose), CDP-alcohols (CDP-glycerol, CDP-ethanolamine, CDP-choline), dinucleotides (diadenosine pyrophosphate, NADH, NAD+, FAD), nucleoside(5') mono- and diphosphates (AMP, CMP, GMP, ADP, CDP) and dTMP p-nitrophenyl ester. Since the enzymes have not been purified to homogeneity, more than three pyrophosphatases may be present, but the co-purification of activities, thermal co-inactivation, and inhibition experiments give support to: (i) and ADP-ribose pyrophosphatase highly specific for ADP(IDP)-ribose in the presence of Mg2+, but active also on non-reducing ADP-hexoses and dinucleotides (not on NAD+) when Mg2+ was replaced with Mn2+; (ii) a Mn(2+)-dependent pyrophosphatase active on ADP(IDP)-ribose, dinucleotides and CDP-alcohols; (iii) a rather unspecific pyrophosphatase that, with Mg2+, was active on AMP(IMP)-containing NDP-sugars and dinucleotides (not on NAD+), and with Mn2+, was also active on non-adenine NDP-sugars and CDP-alcohols. The enzymes differ from nucleotide pyrophosphatase/phosphodiesterase-I (NPPase/PDEaseI) by their substrate specificities and by their cytosolic location and solubility in the absence of detergents. Although NPPase/PDEaseI is much more active in rat liver, its known location in the non-cytoplasmic sides of plasma and endoplasmic reticulum membranes, together with the known cytoplasmic synthesis of NDP-sugars and CDP-alcohols, permit the speculation that the pyrophosphatases studied in this work may have a cellular role.

Phenotypic identification of subclones in multiple myeloma with different chemoresistant, cytogenetic and clonogenic potential.

Knowledge about clonal diversity and selection is critical to understand multiple myeloma (MM) pathogenesis, chemoresistance and progression. If targeted therapy becomes reality, identification and monitoring of intraclonal plasma cell (PC) heterogeneity would become increasingly demanded. Here we investigated the kinetics of intraclonal heterogeneity among 116 MM patients using 23-marker multidimensional flow cytometry (MFC) and principal component analysis, at diagnosis and during minimal residual disease (MRD) monitoring. Distinct phenotypic subclones were observed in 35/116 (30%) newly diagnosed MM patients. In 10/35 patients, persistent MRD was detected after 9 induction cycles, and longitudinal comparison of patient-paired diagnostic vs MRD samples unraveled phenotypic clonal tiding after therapy in half (5/10) of the patients. After demonstrating selection of distinct phenotypic subsets by therapeutic pressure, we investigated whether distinct fluorescence-activated cell-sorted PC subclones had different clonogenic and cytogenetic profiles. In half (5/10) of the patients analyzed, distinct phenotypic subclones showed different clonogenic potential when co-cultured with stromal cells, and in 6/11 cases distinct phenotypic subclones displayed unique cytogenetic profiles by interphase fluorescence in situ hybridization, including selective del(17p13). Collectively, we unravel potential therapeutic selection of preexisting diagnostic phenotypic subclones during MRD monitoring; because phenotypically distinct PCs may show different clonogenic and cytogenetic profiles, identification and follow-up of unique phenotypic-genetic myeloma PC subclones may become relevant for tailored therapy.

Development and psychometric validation of a brief comprehensive health status assessment scale in older patients with hematological malignancies: The GAH Scale.

OBJECTIVES: The purpose of this study was to develop a new brief, comprehensive geriatric assessment scale for older patients diagnosed with different hematological malignancies, the Geriatric Assessment in Hematology (GAH scale), and to determine its psychometric properties. MATERIALS AND METHODS: The 30-item GAH scale was designed through a multi-step process to cover 8 relevant dimensions. This is an observational study conducted in 363 patients aged≥65years, newly diagnosed with different hematological malignancies (myelodysplasic syndrome/acute myeloblastic leukemia, multiple myeloma, or chronic lymphocytic leukemia), and treatment-naïve. The scale psychometric validation process included the analyses of feasibility, floor and ceiling effect, validity and reliability criteria. RESULTS: Mean time taken to complete the GAH scale was 11.9±4.7min that improved through a learning-curve effect. Almost 90% of patients completed all items, and no floor or ceiling effects were identified. Criterion validity was supported by reasonable correlations between the GAH scale dimensions and three contrast variables (global health visual analogue scale, ECOG and Karnofsky), except for comorbidities. Factor analysis (supported by the scree plot) revealed nine factors that explained almost 60% of the total variance. Moderate internal consistency reliability was found (Cronbach's α: 0.610), and test-retest was excellent (ICC coefficients, 0.695-0.928). CONCLUSION: Our study suggests that the GAH scale is a valid, internally reliable and a consistent tool to assess health status in older patients with different hematological malignancies. Future large studies should confirm whether the GAH scale may be a tool to improve clinical decision-making in older patients with hematological malignancies.