We propose a new robust and accurate SPH scheme, able to track correctly complex three-dimensional non-hydrostatic free surface flows and, even more important, also able to compute an accurate and ...little oscillatory pressure field. It uses the explicit third order TVD Runge–Kutta scheme in time, following Shu and Osher Shu C-W, Osher S. Efficient implementation of essentially non-oscillatory shock-capturing schemes. J Comput Phys 1988;89:439–71, together with the new key idea of introducing a monotone upwind flux for the density equation, thus removing any artificial viscosity term. For the discretization of the velocity equation, the non-diffusive central flux has been used. A new flexible approach to impose the boundary conditions at solid walls is also proposed. It can handle any moving rigid body with arbitrarily irregular geometry. It does neither produce oscillations in the fluid pressure in proximity of the interfaces, nor does it have a restrictive impact on the stability condition of the explicit time stepping method, unlike the repellent boundary forces of Monaghan Monaghan JJ. Simulating free surface flows with SPH. J Comput Phys 1994;110:399–406. To asses the accuracy of the new SPH scheme, a 3D mesh-convergence study is performed for the strongly deforming free surface in a 3D dam-break and impact-wave test problem providing very good results.
Moreover, the parallelization of the new 3D SPH scheme has been carried out using the message passing interface (MPI) standard, together with a dynamic load balancing strategy to improve the computational efficiency of the scheme. Thus, simulations involving millions of particles can be run on modern massively parallel supercomputers, obtaining a very good performance, as confirmed by a speed-up analysis. The 3D applications consist of environmental flow problems, such as dam-break flows and impact flows against a wall. The numerical solutions obtained with our new 3D SPH code have been compared with either experimental results or with other numerical reference solutions, obtaining in all cases a very satisfactory agreement.
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The contamination of hot water samples with
Legionella spp. was studied in relation to temperature, total hardness, trace element concentrations (iron, zinc, manganese, and copper) and heterotrophic ...plate counts (HPC) at both 22 and 37 °C. Factor analysis and receiver operating characteristic (ROC) curves were used to establish the cut-off of water parameters as predictors for
Legionella contamination.
Legionella spp. was isolated in 194 out of 408 samples (47.5%), with
Legionella pneumophila being the most common (92.8%). After multiple logistic regression analysis, the risk for legionellae colonisation was positively associated with Mn levels >6 μg l
−1, HPC at 22 °C >27 CFU l
−1, and negatively with temperature >55 °C and Cu levels >50 μg l
−1. Multiple regression analysis revealed that
Legionella spp. counts were positively associated with Mn, HPC at 37 °C and Zn and negatively associated with temperature. Only 1 out of the 97 samples (1%) having a Mn concentration, an HPC at 22 °C and an HPC at 37 °C below the respective median values exhibited a
Legionella spp. concentration exceeding 10
4 CFU l
−1
vs. 41 out of the 89 samples (46.1%) with the three parameters above the medians. Our results show a qualitative and quantitative relationship between
Legionella spp., the Mn concentration and heterotrophic plate counts in hot water samples from different buildings, suggesting that these parameters should be included in a water safety plan. The role of manganese in biofilm formation and its possible involvement in the mechanisms favouring
Legionella survival and growth in water niches should be investigated further.
► Frequency and amount of
Legionella contamination in hot water distribution systems.► Relationship between
Legionella and trace elements, particularly manganese.► Quali- and quantitative relationship between
Legionella and heterotrophic bacteria.► Confirm of a negative association of
Legionella with temperature and copper.
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Purpose The FOLL05 trial compared R-CVP (rituximab plus cyclophosphamide, vincristine, and prednisone) with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) and R-FM ...(rituximab plus fludarabine and mitoxantrone) regimens without rituximab maintenance as initial therapy for patients with advanced-stage follicular lymphoma (FL). A previous analysis with a median follow-up of 34 months showed a superior 3-year time to treatment failure, the primary study end point, with R-CHOP and R-FM versus R-CVP and showed R-CHOP to have a better risk-benefit ratio in terms of toxicity than R-FM. We report a post hoc analysis of this trial after a median follow-up of 7 years. Patients and Methods Of the 534 enrolled patients, 504 were evaluable. At the time of analysis, the median follow-up was 84 months (range, 1 to 119 months). Results The 8-year time to treatment failure and progression-free survival rates were 44% (95% CI, 39% to 49%) and 48% (95% CI, 43% to 53%), respectively. The hazard ratio for progression-free survival adjusted by FL International Prognostic Index 2 versus R-CVP was 0.73 for R-CHOP (95% CI, 0.54 to 0.98; P = .037) and 0.67 for R-FM (95% CI, 0.50 to 0.91; P = .009). The 8-year overall survival (OS) rate was 83% (95% CI, 79% to 87%), with no significant differences among study arms. Overall, we observed a higher risk of dying as a result of causes unrelated to lymphoma progression with R-FM versus R-CVP. Conclusion With an 83% 8-year OS rate, long-term follow-up of the FOLL05 trial confirms the favorable outcome of patients with advanced-stage FL treated with immunochemotherapy. The three study arms had similar OS but different activity and toxicity profiles. Patients initially treated with R-CVP had a higher risk of lymphoma progression compared with those receiving R-CHOP, as well as a higher risk of requiring additional therapy.
Marginal zone lymphomas (MZLs) are indolent nonfollicular B-cell lymphomas (INFLs) and have heterogeneous clinical behavior. Recently, time to progression of disease at 24 months (POD24) was ...identified to stratify overall survival (OS) in follicular non-Hodgkin lymphoma and in INFL. Here, we examined the ability of POD24 to predict subsequent OS in a large, international cohort of MZL as part of the NF10 prospective international registry headed by Fondazione Italiana Linfomi (FIL). POD24 was only calculated for MZL patients requiring immediate therapy and was defined as experiencing lymphoma progression within 24 months from diagnosis. Among the 1325 patients enrolled in the NF10 study, we identified 321 patients with MZL for whom immediate therapy was planned right after lymphoma diagnosis. Overall, POD24 was confirmed in 59 patients (18%). Three-year OS for patients with POD24 was 53% with a hazard ratio of 19.5 (95% confidence interval, 8.4-45) compared with patients without POD24 (3-year OS, 95%). Association of POD24 with OS was confirmed for the subgroup of splenic and extranodal MZLs. Assessment of POD24 stratifies subsequent outcome in MZL and identifies a high-risk population. This trial was registered at www.clinicaltrials.gov as #NCT02904577.
•Patients with MZL who experience POD24 from initial systemic therapy have a significantly increased risk of death.•Association of POD24 with survival is confirmed for the main MZL subtypes.
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To prospectively validate the use of a simplified geriatric assessment (sGA) at diagnosis and to integrate it into a prognostic score for older patients with diffuse large B-cell lymphoma (DLBCL).
We ...conducted the prospective Elderly Project study on patients with DLBCL older than 64 years who underwent our Fondazione Italiana Linfomi original geriatric assessment (oGA) (age, Cumulative Illness Rating Scale for Geriatrics, activities of daily living, and instrumental activities of daily living) before treatment. Treatment choice was left to the physician's discretion. The primary end point was overall survival (OS) (ClinicalTrials.gov identifier: NCT02364050).
We analyzed 1,163 patients (median age 76 years), with a 3-year OS of 65% (95% CI, 62 to 68). Because at multivariate analysis on oGA, age > 80 years retained an independent correlation with OS, we also developed a new, simplified version of the GA (sGA) that classifies patients as fit (55%), unfit (28%), and frail (18%) with significantly different 3-year OS of 75%, 58%, and 43%, respectively. The sGA groups, International Prognostic Index, and hemoglobin levels were independent predictors of OS and were used to build the Elderly Prognostic Index (EPI). Three risk groups were identified: low (23%), intermediate (48%), and high (29%), with an estimated 3-year OS of 87% (95% CI, 81 to 91), 69% (95% CI, 63 to 73), and 42% (95% CI, 36 to 49), respectively. The EPI was validated using an independent external series of 328 cases.
The Elderly Project validates sGA as an objective tool to assess fitness status and defines the new EPI to predict OS of older patients with DLBCL.
1 Department of Oncology and Haematology, Hematology Division, University of Modena and Reggio Emilia, Modena
2 Department of Oncology and Haematology, Haematology Division, Civil Hospital of ...Piacenza, Piacenza
3 Department of Oncology and Haematology, Oncology Division, University of Modena and Reggio Emilia, Modena, Italy
Correspondence: Roberto Marasca, MD, Hematology Division, Policlinico, via del Pozzo 71, 41100 Modena, Italy. E-mail: roberto.marasca{at}unimore.it
Imatinib mesylate is a tyrosine kinase inhibitor used as first line treatment in chronic myeloid leukemia and gastrointestinal stromal tumorpatients. Although several in vitro and animal studies demonstrated that imatinib affects immune response, few immune alterations are described in humans. We retrospectively studied hematologic and immunological parameters in 72 chronic myeloid leukemia and 15 gastrointestinal stromal tumor patients treated with imatinib at standard dosage and in 20 chronic myeloid leukemia patients treated before the introduction of imatinib in clinical practice. Both chronic myeloid leukemia and gastrointestinal stromal tumor patients developed a significant reduction of gammaglobulin and immunoglobulin serum levels. No significant hypogammaglobulinemia was observed in chronic myeloid leukemia patients in the pre-imatinib era. These data demonstrate that imatinib treatment induces hypogammaglobulinemia that can reach a severe entity in 10% of cases, both in chronic myeloid leukemia and in gastrointestinal stromal tumor patients. Prospective studies are needed to evaluate immune humoral alterations and to define the real incidence of infectious events, including viral reactivations.
Key words: chronic myeloid leukemia, imatinib, hypogammaglobulinemia.
The randomized HD2000 trial compared six cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), four escalated plus two standard cycles of BEACOPP (bleomycin, etoposide, doxorubicin, ...cyclophosphamide, vincristine, procarbazine, and prednisone), and six cycles of COPP-EBV-CAD (cyclophosphamide, lomustine, vindesine, melphalan, prednisone, epidoxorubicin, vincristine, procarbazine, vinblastine, and bleomycin; CEC) in patients with advanced-stage Hodgkin lymphoma. After a median follow-up of 42 months, patients who received BEACOPP were reported to have experienced better progression-free survival (PFS) but not better overall survival (OS) results than those receiving ABVD. We here report a post hoc analysis of this trial after a median follow-up of 10 years.
Three hundred seven patients were enrolled, 295 of whom were evaluable. At the time of our analysis, the median follow-up for the entire group was 120 months (range, 4 to 169 months).
The 10-year PFS results for the ABVD, BEACOPP, and CEC arms were 69%, 75%, and 76%, respectively; corresponding OS results were 85%, 84%, and 86%. Overall, 13 second malignancies were reported: one in the ABVD arm and six each in the BEACOPP and CEC arms. The cumulative risk of developing second malignancies at 10 years was 0.9%, 6.6%, and 6% with ABVD, BEACOPP, and CEC, respectively; the risk with either BEACOPP or CEC was significantly higher than that reported with ABVD (P = .027 and .02, respectively).
With these mature results, we confirm that patients with advanced Hodgkin lymphoma have similar OS results when treated with ABVD, BEACOPP, or CEC. However, with longer follow-up, we were not able to confirm the superiority of BEACOPP over ABVD in terms of PFS, mainly because of higher mortality rates resulting from second malignancies observed after treatment with BEACOPP and CEC.
Selenium (Se) is a trace element with different toxicological and nutritional properties according to its chemical forms. Among the wide range of selenium species, human serum albumin-bound selenium ...(Se-HSA) has still uncertain composition in terms of organic or inorganic selenium species. This study aimed at investigating the relation between Se-HSA levels with total selenium and the specific organic and inorganic selenium species.
We determined levels of total selenium and selenium species in serum of participants enrolled in two populations of the Emilia-Romagna region, in Northern Italy. Anion exchange chromatography coupled with inductively coupled plasma dynamic reaction cell mass spectrometry was used as quantification method. Correlations between Se-HSA and the other selenium compounds were analyzed using linear regression and restricted cubic spline regression models, adjusted for potential confounders.
The first cohort comprised 50 participants (men/women: 26/24) with median (interquartile range, IQR) age 50 (55−62) years, while the second was composed of 104 participants (M/W: 50/54), median (IQR) age 48 (44−53) years. Median (IQR) levels of total selenium were 118.5 (109−136) µg/L and 116.5 (106−128) µg/L, respectively, while Se-HSA was 25.5 µg/L (16.2–51.5) and 1.1 (0.03–3.1) µg/L, respectively. In both populations, Se-HSA was positively associated with inorganic selenium species. Conversely, Se-HSA was inversely associated with organic selenium, especially with selenoprotein P-bound-Se (Se-SELENOP) and less strongly with selenomethionine-bound-Se (Se-Met), while the relation was null or even positive with other organic species. Evaluation of non-linear trends showed a substantially positive association with inorganic selenium, particularly selenite, until a concentration of 30 µg/L, above which a plateau was reached. The association with Se-SELENOP was inverse and strong until 100 µg/L, while it was almost null at higher levels.
Our findings seem to indicate that Se-HSA incorporates more selenium when circulating levels of inorganic compounds are higher, thus supporting its mainly inorganic nature, particularly at high circulating levels of selenite.
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A cross-sectional biomonitoring study was performed in Modena (Italy) to assess trace element levels in toenails in a population living near a municipal solid waste incinerator (SWI), and investigate ...potential differences in their concentrations according to SWI emission exposure and other environmental and behavioral factors.
During the winter 2013/14 eligible subjects, aged 18–69 yrs, living within 4 km from SWI, were randomly selected from the population register. Toxic and essential element concentrations (As, Cd, Cr, Cu, Mn, Ni, Pb, Se, Zn) were analyzed in 489 toenail samples. Individual exposure to SWI emissions was estimated by using, as a tracer, fall-out maps of emitted particulate matter. Information on anthropometric parameters, lifestyles, diet, and road traffic, residential and work exposures were collected by questionnaires and objective measurements. Multivariate logistic regression analyses were carried out, separately for females and males.
Excluding As, toxic elements were found, usually at low levels, in many samples, while essential elements, especially Cu and Zn, showed higher levels. Overall, no clear relationships between element levels and SWI exposure were observed, whereas associations with other environmental and lifestyle factors were found, including local food consumption, smoking and occupation.
The low pollutant concentrations measured in SWI emissions could explain the absence of clear patterns in toenail levels across SWI exposure levels. The associations observed with other factors suggest that, at least in this specific population, other environmental exposures and personal behaviors could act as more important predictors of trace element uptake.
•Biomonitoring on 489 subjects living near a modern solid waste incinerator (SWI).•Several trace elements were quantified in toenails, a matrix of long-term exposure.•A wide array of confounders and concomitant sources of exposure were assessed.•No association between trace elements in toenails and SWI emission was found.•Associations with other environmental and behavioral sources of exposure were found.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
L’obiettivo di questo articolo è quello di indagare la dimensione linguistico-comunicativa della matematica in un genere testuale fondamentale in didattica: il libro di testo. Nello specifico, ...verranno osservate parti selezionate di un corpus di testi scolastici di matematica per la scuola primaria e secondaria di primo grado al fine di descriverne e analizzarne le caratteristiche strutturali e compositive. Più in particolare, lo scopo è quello di proporre un modello di articolazione dei libri scolastici di matematica, che prenda le mosse dai più recenti studi di linguistica testuale, individuandone le unità compositive basilari e caratterizzanti: ciò risulta fondamentale per poter valutare l’adeguatezza dei testi stessi per i loro destinatari, e per avviare ulteriori indagini su aspetti matematici e linguistici mirati. Quest’analisi si inserisce nell’ambito del progetto Italmatica. Comprendere la matematica a scuola tra lingua comune e linguaggio specialistico (sostenuto dal Fondo Nazionale Svizzero per la Ricerca Scientifica), che non ha solo un fine descrittivo, ma si prefigge anche di indagare se e come determinate scelte linguistico-testuali possono avere effetti sulla comprensione e sull’acquisizione del sapere matematico da parte di allieve e allievi. The architecture of the school textbook of mathematics for primary and secondary schools The aim of this article is to investigate the linguistic-communicative dimension of mathematics in a text genre crucial in didactics: the textbook. Specifically, we will observe selected parts of mathematics textbooks for primary and secondary school (junior high school), collected in a corpus, in order to describe their structural and compositional characteristics. More specifically, the aim is to propose a model for the articulation of mathematical textbooks, starting from the most recent studies of textual linguistics, identifying their fundamental and characterizing compositional units. This study is necessary in order to assess the suitability of texts for their target audience, as a starting point for further investigations on selected mathematical and linguistic aspects and features. This analysis is part of the Italmatica. Comprendere la matematica a scuola tra lingua comune e linguaggio specialistico (supported by the Swiss National Science Foundation), whose goal is not only descriptive, but also to investigate whether and how certain linguistic and textual choices impact on student understanding and the acquisition of mathematical knowledge.
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