Improvement of powertrain mechatronic systems for lean automotive manufacturing

In recent years, the increasing severity of emission standards forced car manufacturers to integrate vehicle powertrains with additional mechatronic elements, consisting in sensors, executors and controlling elements interacting with each other. However, the introduction of the best available ecological devices goes hand in hand with the legislation and/or limitations in different regional markets. Thus, the designers adapt the mechatronic system to the target emission standards of the produced powertrain. The software embedded into the Engine Control Unit (ECU) is highly customized for the specific configurations: variability in mechatronic systems leads to the development of several software versions, lowering the efficiency of the design phase. Therefore the employment of a standard for the communication among sensors, actuators and the ECU would allow the development of a unique software for different configurations; this would be beneficial from a manufacturing point of view, enabling the simplification of the design process. Obviously, the new software must still guarantee the proper level of feedbacks to the ECU to ensure the compliance with different emission standards and the proper engine behavior. The general software is adapted to the powertrain: according to the specific target emission standard, some control elements may not be necessary, and a part of the software may be easily removed. In this paper, starting from a real case-study, a more general methodology is proposed for configurations characterized by different powertrain sets and manufacturing line constraints. The proposed technique allows to maintain the accuracy of the control system and improve process efficiency at the same time, ensuring lean production and lowering manufacturing costs. A set of mathematical techniques to improve software efficacy is also presented: the resulting benefits are enhanced by software standardization, because the design effort may be shared by the largest possible number of applications

Clinical and economic outcomes associated with malnutrition in hospitalized patients

Background & aims: Hospitalized patients show a high rate of malnutrition, which is associated with poor patient outcomes and high healthcare costs. However, relatively few studies have investigated the association between clinical and economic outcomes and malnutrition in hospitalized patients, particularly those with cardiac and pulmonary conditions. Methods: This multicenter prospective observational cohort study included 800 patients hospitalized at four Colombian hospitals with a diagnosis of congestive heart failure, acute myocardial infarction, community-acquired pneumonia, or chronic obstructive pulmonary disease. All patients were screened for malnutrition using the Malnutrition Screening Tool (MST). A descriptive analysis of baseline variables was followed by multivariate analysis and inverse probability weighting (IPW) to compare the clinical outcomes, i.e., length of stay (LOS), mortality, and readmission, and hospital costs associated with a positive MST result. Results: The prevalence of a positive MST result was 24.62% (n ¼ 197) and was more common in patients with older age and greater comorbidities. Multivariate analysis controlling for age, gender, healthcare plan, university degree, hospitalization, entrance disease and Charlson co-morbidity index showed that a positive MST result was associated with increased LOS (1.43 ± 0.61 days) and both in-hospital mortality (odds ratio, 2.39) and global mortality (odds ratio, 2.52). IPW analysis confirmed the association between a positive MST result and increased hospital LOS and 30-day mortality, as well as a relative increase of 30.13% in the average cost associated with hospitalization. Conclusions: This study of hospital inpatients demonstrated a high burden of malnutrition at the time of hospital admission, which negatively impacted LOS and mortality and increased the costs of hospitalization. These findings underscore the need for improved diagnosis and treatment of hospital malnutrition to improve patient outcomes and reduce healthcare costs

Multiple myeloma primary cells show a highly rearranged unbalanced genome with amplifications and homozygous deletions irrespective of the presence of immunoglobulin-related chromosome translocations

Background and Objectives Multiple myeloma (MM) is a malignant plasma cell neoplasia in which genetic studies have shown that genomic changes may affect almost all chromosomes, as shown by fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH). Our objective was the genomic characterization of CD 138 positive primary MM samples by means of a high resolution array CGH platform. Design and Methods For the first time, a high resolution array CGH with more than 40,000 probes, has been used to analyze 26 primary MM samples after the enrichment of CD138-positive plasma cells. Results This approach identified copy number imbalances in all cases. Bioinformatics strategies were optimized to perform data analysis allowing the segregation of hyperdiploid and non-hyperdiploid cases by array CGH. Additional analysis showed that structural chromosome rearrangements were more frequently seen in hyperdiploid cases. We also identified the same Xq21 duplication in nearly 20% of the cases, which originated through unbalanced chromosome translocations. High level amplifications and homozygous deletions were recurrently observed in our series and involved genes with meaningful function in cancer biology. Interpretation and Conclusions High resolution array CGH allowed us to identify copy number changes in 100% of the primary MM samples. We segregated different MM subgroups based on their genomic profiles which made it possible to identify homozygous deletions and amplifications of great genetic relevance in MM

A comprehensive microarray-based DNA methylation study of 367 hematological neoplasms

Background: Alterations in the DNA methylation pattern are a hallmark of leukemias and lymphomas. However, most epigenetic studies in hematologic neoplasms (HNs) have focused either on the analysis of few candidate genes or many genes and few HN entities, and comprehensive studies are required. Methodology/Principal Findings: Here, we report for the first time a microarray-based DNA methylation study of 767 genes in 367 HNs diagnosed with 16 of the most representative B-cell (n = 203), T-cell (n = 30), and myeloid (n = 134) neoplasias, as well as 37 samples from different cell types of the hematopoietic system. Using appropriate controls of B-, T-, or myeloid cellular origin, we identified a total of 220 genes hypermethylated in at least one HN entity. In general, promoter hypermethylation was more frequent in lymphoid malignancies than in myeloid malignancies, being germinal center mature B-cell lymphomas as well as B and T precursor lymphoid neoplasias those entities with highest frequency of gene-associated DNA hypermethylation. We also observed a significant correlation between the number of hypermethylated and hypomethylated genes in several mature B-cell neoplasias, but not in precursor B- and T-cell leukemias. Most of the genes becoming hypermethylated contained promoters with high CpG content, and a significant fraction of them are targets of the polycomb repressor complex. Interestingly, T-cell prolymphocytic leukemias show low levels of DNA hypermethylation and a comparatively large number of hypomethylated genes, many of them showing an increased gene expression. Conclusions/Significance: We have characterized the DNA methylation profile of a wide range of different HNs entities. As well as identifying genes showing aberrant DNA methylation in certain HN subtypes, we also detected six genes—DBC1, DIO3, FZD9, HS3ST2, MOS, and MYOD1—that were significantly hypermethylated in B-cell, T-cell, and myeloid malignancies. These might therefore play an important role in the development of different HNs

The polo-like kinase 1 (PLK1) inhibitor NMS-P937 is effective in a new model of disseminated primary CD56+ acute monoblastic leukaemia

CD56 is expressed in 15–20% of acute myeloid leukaemias (AML) and is associated with extramedullary diffusion, multidrug resistance and poor prognosis. We describe the establishment and characterisation of a novel disseminated model of AML (AML-NS8), generated by injection into mice of leukaemic blasts freshly isolated from a patient with an aggressive CD56+ monoblastic AML (M5a). The model reproduced typical manifestations of this leukaemia, including presence of extramedullary masses and central nervous system involvement, and the original phenotype, karyotype and genotype of leukaemic cells were retained in vivo. Recently Polo-Like Kinase 1 (PLK1) has emerged as a new candidate drug target in AML. We therefore tested our PLK1 inhibitor NMS-P937 in this model either in the engraftment or in the established disease settings. Both schedules showed good efficacy compared to standard therapies, with a significant increase in median survival time (MST) expecially in the established disease setting (MST = 28, 36, 62 days for vehicle, cytarabine and NMS-P937, respectively). Importantly, we could also demonstrate that NMS-P937 induced specific biomarker modulation in extramedullary tissues. This new in vivo model of CD56+ AML that recapitulates the human tumour lends support for the therapeutic use of PLK1 inhibitors in AML

Bayesian segmented regression model to evaluate the adaptability and stability of maize in Northeastern Brazil.

Although maize is one of the main crops in the Northeast region, yield is still considered low when compared to other regions. One of the main solutions to increasing yield is the selection of cultivars adapted to the conditions of the Northeast region. Thus, the present study aims to use the Bayesian segmented regression model to evaluate the adaptability and stability of maize

DNA Methylation Profiles and Their Relationship with Cytogenetic Status in Adult Acute Myeloid Leukemia

Background: Aberrant promoter DNA methylation has been shown to play a role in acute myeloid leukemia (AML) pathophysiology. However, further studies to discuss the prognostic value and the relationship of the epigenetic signatures with defined genomic rearrangements in acute myeloid leukemia are required. Methodology/Principal Findings: We carried out high-throughput methylation profiling on 116 de novo AML cases and we validated the significant biomarkers in an independent cohort of 244 AML cases. Methylation signatures were associated with the presence of a specific cytogenetic status. In normal karyotype cases, aberrant methylation of the promoter of DBC1 was validated as a predictor of the disease-free and overall survival. Furthermore, DBC1 expression was significantly silenced in the aberrantly methylated samples. Patients with chromosome rearrangements showed distinct methylation signatures. To establish the role of fusion proteins in the epigenetic profiles, 20 additional samples of human hematopoietic stem/ progenitor cells (HSPC) transduced with common fusion genes were studied and compared with patient samples carrying the same rearrangements. The presence of MLL rearrangements in HSPC induced the methylation profile observed in the MLL-positive primary samples. In contrast, fusion genes such as AML1/ETO or CBFB/MYH11 failed to reproduce the epigenetic signature observed in the patients. Conclusions/Significance: Our study provides a comprehensive epigenetic profiling of AML, identifies new clinical markers for cases with a normal karyotype, and reveals relevant biological information related to the role of fusion proteins on the methylation signatur

Clinical and economic outcomes associated with malnutrition in hospitalized patients

Q1Q1Artículo original1310–1316DesnutriciónBackground & aims: Hospitalized patients show a high rate of malnutrition, which is associated with poor patient outcomes and high healthcare costs. However, relatively few studies have investigated the association between clinical and economic outcomes and malnutrition in hospitalized patients, particularly those with cardiac and pulmonary conditions. Methods: This multicenter prospective observational cohort study included 800 patients hospitalized at four Colombian hospitals with a diagnosis of congestive heart failure, acute myocardial infarction, community-acquired pneumonia, or chronic obstructive pulmonary disease. All patients were screened for malnutrition using the Malnutrition Screening Tool (MST). A descriptive analysis of baseline variables was followed by multivariate analysis and inverse probability weighting (IPW) to compare the clinical outcomes, i.e., length of stay (LOS), mortality, and readmission, and hospital costs associated with a positive MST result. Results: The prevalence of a positive MST result was 24.62% (n ¼ 197) and was more common in patients with older age and greater comorbidities. Multivariate analysis controlling for age, gender, healthcare plan, university degree, hospitalization, entrance disease and Charlson co-morbidity index showed that a positive MST result was associated with increased LOS (1.43 ± 0.61 days) and both in-hospital mortality (odds ratio, 2.39) and global mortality (odds ratio, 2.52). IPW analysis confirmed the association between a positive MST result and increased hospital LOS and 30-day mortality, as well as a relative increase of 30.13% in the average cost associated with hospitalization. Conclusions: This study of hospital inpatients demonstrated a high burden of malnutrition at the time of hospital admission, which negatively impacted LOS and mortality and increased the costs of hospitalization. These findings underscore the need for improved diagnosis and treatment of hospital malnutrition to improve patient outcomes and reduce healthcare costs

Continuous hydrothermal flow synthesis of S-functionalised carbon quantum dots for enhanced oil recovery

Currently, there is a paucity in the exploration and application of carbon-based nanomaterials for enhanced oil recovery. Carbon quantum dots (CQDs), 0D materials consisting of a graphitic core covered by an amorphous carbon framework, were produced from glucose and p-sulfonic acid calix[4]arene (SCX4) via Continuous Hydrothermal Flow Synthesis (CHFS), an environmentally benign synthetic approach. The S-functionalised carbon quantum dots (S-CQDs) demonstrated excellent colloidal stability in aqueous and brine solutions, low retention on sand surface, and impressive enhanced oil recovery (EOR) of 17% at very low concentrations of 0.01 wt%. The mechanisms proposed for CQDs in increasing oil sweeping efficiency involves altering the carbonate rocks wettability towards water wet, and creating temporary log-jamming, where the ultra-small particle size (1.7 ± 0.7 nm) allows S-CQDs to recover oil trapped in tight reservoirs. The synthesised S-CQDs also demonstrate photoluminescence, pH stability in the range of 3–11 and have excitation independent behaviour (300–360 nm) with an emission peak at 433 nm

The occurrence of germline BRCA1 and BRCA2 sequence alterations in Slovenian population

<p>Abstract</p> <p>Background</p> <p>The <it>BRCA1 </it>and <it>BRCA2 </it>mutation spectrum and mutation detection rates according to different family histories were investigated in 521 subjects from 322 unrelated Slovenian cancer families with breast and/or ovarian cancer.</p> <p>Methods</p> <p>The <it>BRCA1 </it>and <it>BRCA2 </it>genes were screened using DGGE, PTT, HRM, MLPA and direct sequencing.</p> <p>Results</p> <p>Eighteen different mutations were found in <it>BRCA1 </it>and 13 in <it>BRCA2 </it>gene. Mutations in one or other gene were found in 96 unrelated families. The mutation detection rates were the highest in the families with at least one breast and at least one ovarian cancer - 42% for <it>BRCA1 </it>and 8% for <it>BRCA2</it>. The mutation detection rate observed in the families with at least two breast cancers with disease onset before the age of 50 years and no ovarian cancer was 23% for <it>BRCA1 </it>and 13% for <it>BRCA2</it>. The mutation detection rate in the families with at least two breast cancers and only one with the disease onset before the age of 50 years was 11% for <it>BRCA1 </it>and 8% for <it>BRCA2</it>. In the families with at least two breast cancers, all of them with disease onset over the age of 50 years, the detection rate was 5% for <it>BRCA2 </it>and 0% for <it>BRCA1</it>.</p> <p>Conclusion</p> <p>Among the mutations detected in Slovenian population, 5 mutations in <it>BRCA1 </it>and 4 mutations in <it>BRCA2 </it>have not been described in other populations until now. The most frequent mutations in our population were c.181T > G, c.1687C > T, c.5266dupC and c.844_850dupTCATTAC in <it>BRCA1 </it>gene and c.7806-2A > G, c.5291C > G and c.3978insTGCT in <it>BRCA2 </it>gene (detected in 69% of <it>BRCA1 </it>and <it>BRCA2 </it>positive families).</p