R&D and innovation project selection: can optimization methods be adequate?

This article proposes a comprehensive framework for R&D and innovation project selection under uncertainty and subject to real-world constraints applicable to the Brazilian electricity sector, using a combination of integer programming formulation and a PROMETHEE-based method. The objective is to contribute to this domain by offering an approach suitable for the challenges of this sector, but also applicable to other situations involving R&D and innovation investments under similar conditions. The manuscript presents applications using real data from an electricity company. It also compares the proposed method with similar approaches found in the literature such as PROMETHEE II and V. The application revealed the best performance of the proposed framework in dealing with the sector's regulatory constraints, which emphasize the companies' accomplishment with R&D and innovation expenditures obligations. In this way, although R&D and innovation project selection is not a typical case of optimization, under some particular regional, sector-based or organization boundaries this can be a better solution. (C) 2015 Published by Elsevier B.V.This article proposes a comprehensive framework for R&D and innovation project selection under uncertainty and subject to real-world constraints applicable to the Brazilian electricity sector, using a combination of integer programming formulation and a P55613621sem informaçãosem informaçã

Metabolic syndrome and risk of cancer : A study protocol of case-control study using data from the Information System for the Development of Research in Primary Care (SIDIAP) in Catalonia

Funding The project received a research grant from the Carlos III Institute of Health, Ministry of Economy and Competitiveness (Spain), awarded on the 2017 call under the Health Strategy Action 2013-2016 of the National Research Program oriented to Societal Challenges, within the Technical, Scientific and Innovation Research National Plan 2013-2016 (reference PI17/00914), cofunded with European Union ERDF funds (European Regional Development Fund). TD-S is funded by the Department of Health of the Generalitat de Catalunya, awarded on the 2016 call under the Strategic Plan for Research and Innovation in Health (PERIS) 2016-2020, modality incorporation of scientists and technologists, with reference SLT002/16/00308.Background Metabolic syndrome (MS) is defined by the clustering of specific metabolic disorders in one subject. MS is highly prevalent globally and currently considered a growing public health concern. MS comprises obesity, hypertension, dyslipidaemia and insulin resistance. Mechanisms linking MS with cancer are poorly understood, and it is as yet unknown if MS confers a greater risk than the risk entailed by each of its separate components. The main objective of this study is to compare the association between MS and 14 site-specific cancer against the association between one or two individual components of MS and cancer. The secondary objective is to evaluate the time elapsed since the diagnosis of MS and the subsequent onset of cancer within the 2006-2017 period by sex. Methods and analysis A case-control study will be conducted for the main objective and a cohort of patients with MS will be followed for the evaluation of the second objective. Incident cases of fourteen types of cancer in patients ≥40 years of age diagnosed prospectively will be selected from electronic primary care records in the Information System for Research in Primary Care (SIDIAP database; www.sidiap.org). The SIDIAP database includes anonymous data from 6 million people (80% of the Catalan population) registered in 286 primary healthcare centres. Each matched control (four controls for each case) will have the same inclusion date, the same sex and age (±1 year) than the paired case. Logistic regression and a descriptive analysis and Kaplan-Meier analysis will be performed, in accordance with the objectives. Ethics and dissemination The protocol of the study was approved by the IDIAP Jordi Gol Clinical Research Ethics Committee (protocol P17/212). The study's findings will be published in a peer-reviewed journal and disseminated at national and international conferences and oral presentations to researchers, clinicians and policy makers

Fracture of upper central incisor permanent: Case report

The cases of root fractures in odontology are extremely serious and require, besides of an accurate diagnosis, the immediate and correct assistance in order to get a good prognostic of  the  case.  A  male,  30  years  old,  went  to  the  dentist  office  after  a  permanent  right  maxillary central incisor trauma. The tooth was examined and semiotechnique tests were done, periapical and exchange of contention. After seven days, it was made a canal preparation and medication with  calcium  hydroxide  paste.  After  four  months,  it  was  arranged  in  the  filling  of  the  coronal portion and later proservation of the case for two years, and we noted the normal tissue and repair the fracture area. In cases of dental trauma involving root fracture, it is preciput that we make  the  same  diagnosis  and  a  rigid  restraint  as  soon  as  possible  to  stabilize  the  fragment  in   the  region.  In  this  case  reported,  the  short  time  that  the  tooth  fragment  was  out  of  the  socket placement of an intracanal medication and right immobilization were crucial factors for good prognosis

Wear analysis promoted in simulated canals apical third after endodontic preparation with K3 Taper .04 System

The authors analyzed the wear in apical third after K3 .04 System preparation. 12 sets of instruments were used and 12 simulated canals in transparent epoxy resin blocks with angles of curvature 20 and 40 degrees. Canals were photographed before preparation and after the utilization of instruments which prepared the apical stop: 30, 35, 40 e 45. The images were overposed in Adobe Photoshop program and the wear was measured in millimeters, in two points, 1 (A) and 5 (B) millimeters from the working length. By Variance Analysis the interaction existence was studied among these three factors: canal curvature, instrument caliber and curve location. In canals of 20 degrees, in both analyzed points, the wear mean promoted by instrument 40 and instrument 35 there was not statistically significant. In canals of 40 degrees, in location A, there was not statistically significant difference in the wear mean promoted by four different instruments. There was a deviation from the original trajectory to the outside the curve, in both analyzed points

Wear promoted in the apical third of simulated canals after instrumentation with protaper universal system

OBJECTIVE: This study evaluated the wear in the apical third of simulate canals after preparation with ProTaper Universal Rotary System. MATERIAL AND METHODS: 24 sets of instruments were used in 24 simulated canals in transparent epoxy resin blocks with degree of curvature of either 20°or 40°. The canals were photographed preoperatively and after preparation of the apical stop with ProTaper F3, F4 and F5 instruments. The initial and final images were exported to Adobe Photoshop® software and superimposed to detect the root canal wall differences (in mm) between them, in two points located 1 (A) and 5 (B) mm from the point where the working length was established. Data were subjected to analysis of variance to verify the existence of interaction among the factors: canal curvature, instrument size and curve location. Significant level was set at 5%. RESULTS: Regardless of the location and the canal curvature, F4 and F5 instruments produced the greatest wear (

Produção e qualidade de alfafa em função da adubação nitrogenada e da simbiose com Sinorhizobium meliloti

A eficiência do processo simbiótico entre a alfafa (Medicago sativa L.) e a bactéria Sinorhizobium meliloti pode ser afetada pela presença de nitrogênio no solo. Avaliou-se a contribuição da simbiose em comparação à adubação nitrogenada em componentes da produção de alfafa, em dois experimentos sob condições controladas e um terceiro em campo. Sob condições controladas, verificou-se efeito positivo da adubação nitrogenada sobre as variáveis estudadas, sobre a produção de matéria seca, teor de nitrogênio e proteína. Em campo, verificou-se efeito negativo do N-mineral (450 kg ha-1 ano-1) sobre o processo simbiótico, com redução da nodulação e atividade da enzima nitrogenase, sem efeito sobre a produção de matéria seca, nitrogênio total, proteína bruta, nitrogênio não protéico e digestibilidade. O desempenho dos cultivares estudados foi semelhante nos dois ambientes de estudo, sendo os cultivares Crioula Brasileira e Crioula Chilena os mais produtivos e o cultivar Pioneer-5454 como o de melhor valor nutritivo da biomassa produzida. Adubação nitrogenada é dispensável para Medicago sativa inoculada com a bactéria fixadora de nitrogênio correspondente, uma vez que a simbiose pode garantir o fornecimento de nitrogênio em quantidade suficiente para a produção.The efficiency of the symbiotic process between alfalfa (Medicago sativa L.) and Sinorhizobium meliloti can be drastically affected by soil nitrogen. This research evaluates how mineral fertilization affects the contribution of symbiosis to the yield and quality of alfalfa in two experiments under controlled conditions, and a third one in the field. Under controlled conditions, positive effect of nitrogen fertilizer was observed, whereas, in the field, negative effect of the mineral nitrogen (450 kg ha-1 year-1) on the symbiotic process was observed, with reduction of nodulation and nitrogenase activity. However, there was no effect on yield, total nitrogen concentration, crude protein, non-protein nitrogen and digestibility in relation to the treatment without mineral N. The cultivars showed similar performance under different conditions, with 'Crioula Brasileira' and 'Crioula Chilena' showing the highest yield and 'Pioneer-5454' the highest forage nutritive value

Body mass index and waist circumference in relation to the risk of 26 types of cancer : a prospective cohort study of 3.5 million adults in Spain

A high body mass index (BMI) has been associated with increased risk of several cancers; however, whether BMI is related to a larger number of cancers than currently recognized is unclear. Moreover, whether waist circumference (WC) is more strongly associated with specific cancers than BMI is not well established. We aimed to investigate the associations between BMI and 26 cancers accounting for non-linearity and residual confounding by smoking status as well as to compare cancer risk estimates between BMI and WC. Prospective cohort study with population-based electronic health records from Catalonia, Spain. We included 3,658,417 adults aged ≥ 18 years and free of cancer at baseline between 2006 and 2017. Our main outcome measures were cause-specific hazard ratios (HRs) with 99% confidence intervals (CIs) for incident cancer at 26 anatomical sites. After a median follow-up time of 8.3 years, 202,837 participants were diagnosed with cancer. A higher BMI was positively associated with risk of nine cancers (corpus uteri, kidney, gallbladder, thyroid, colorectal, breast post-menopausal, multiple myeloma, leukemia, non-Hodgkin lymphoma) and was positively associated with three additional cancers among never smokers (head and neck, brain and central nervous system, Hodgkin lymphoma). The respective HRs (per 5 kg/m 2 increment) ranged from 1.04 (99%CI 1.01 to 1.08) for non-Hodgkin lymphoma to 1.49 (1.45 to 1.53) for corpus uteri cancer. While BMI was negatively associated to five cancer types in the linear analyses of the overall population, accounting for non-linearity revealed that BMI was associated to prostate cancer in a U-shaped manner and to head and neck, esophagus, larynx, and trachea, bronchus and lung cancers in an L-shaped fashion, suggesting that low BMIs are an approximation of heavy smoking. Of the 291,305 participants with a WC measurement, 27,837 were diagnosed with cancer. The 99%CIs of the BMI and WC point estimates (per 1 standard deviation increment) overlapped for all cancers. In this large Southern European study, a higher BMI was associated with increased risk of twelve cancers, including four hematological and head and neck (only among never smokers) cancers. Furthermore, BMI and WC showed comparable estimates of cancer risk associated with adiposity. Supplementary information accompanies this paper at 10.1186/s12916-020-01877-3

Passion fruit (Passiflora edulis) leaf extract modulates the oxidative metabolism of rat peritoneal neutrophils in a model of inflammation

This study was conducted to evaluate the effect of extracts of Passiflora edulis Sims leaves on the oxidative metabolism of rat peritoneal neutrophils using a model of acute inflammation. The extract was obtained by maceration in 70% ethanol, evaporation under reduced pressure and lyophilisation. Total phenolic content (TP) was determined by the Folin-Ciocalteu assay. The P. edulis extract, in different doses, was administered by gavage 1 h prior to inflammation induction by carrageenan (8 mg/kg, i.p.); five hours later, the neutrophils were obtained by intraperitoneal lavage. The tests performed in neutrophils were cytochrome C and chemiluminescence assay as well as myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) activities. The administration of the extract reduced the number of neutrophils recruited to the site of inflammation; however, the extract did not alter the activity of NADPH oxidase as well as SOD activity in these cells. The MPO and CAT activities in peritoneal neutrophils of rat treated with extract was lower than in the control group, and the GPx activity was increased. Based on the experimental model utilised, the anti-inflammatory potential of P. edulis leaf extract could be related to the presence of phenolic compounds in the extract

Association between metabolic syndrome and 13 types of cancer in Catalonia : A matched case-control study

Metabolic syndrome (MS) is the simultaneous occurrence of a cluster of predefined cardiovascular risk factors. Although individual MS components are associated with increased risk of cancer, it is still unclear whether the association between MS and cancer differs from the association between individual MS components and cancer. The aim of this matched case-control study was to estimate the association of 13 types of cancer with (1) MS and (2) the diagnosis of 0, 1 or 2 individual MS components. Cases included 183,248 patients ≥40 years from the SIDIAP database with incident cancer diagnosed between January 2008-December 2017. Each case was matched to four controls by inclusion date, sex and age. Adjusted conditional logistic regression models were used to evaluate the association between MS and cancer risk, comparing the effect of global MS versus having one or two individual components of MS. MS was associated with an increased risk of the following cancers: colorectal (OR: 1.28, 95%CI: 1.23-1.32), liver (OR: 1.93, 95%CI: 1.74-2.14), pancreas (OR: 1.79, 95%CI: 1.63-1.98), post-menopausal breast (OR: 1.10, 95%CI: 1.06-1.15), pre-menopausal endometrial (OR: 2.14, 95%CI: 1.74-2.65), post-menopausal endometrial (OR: 2.46, 95%CI: 2.20-2.74), bladder (OR: 1.41, 95%CI: 1.34-1.48), kidney (OR: 1.84, 95%CI: 1.69-2.00), non-Hodgkin lymphoma (OR: 1.23, 95%CI: 1.10-1.38), leukaemia (OR: 1.42, 95%CI: 1.31-1.54), lung (OR: 1.11, 95%CI: 1.05-1.16) and thyroid (OR: 1.71, 95%CI: 1.50-1.95). Except for prostate, pre-menopause breast cancer and Hodgkin and non-Hodgkin lymphoma, MS is associated with a higher risk of cancer than 1 or 2 individual MS components. Estimates were significantly higher in men than in women for colorectal and lung cancer, and in smokers than in non-smokers for lung cancer. MS is associated with a higher risk of developing 11 types of common cancer, with a positive correlation between number of MS components and risk of cancer

Drug Utilisation Patterns of Alternatives to Ranitidine-Containing Medicines in Patients Treated with Ranitidine:A Network Analysis of Data from Six European National Databases

Introduction: Ranitidine, a histamine H2-receptor antagonist (H2RA), is indicated in the management of gastric acid-related disorders. In 2020, the European Medicines Agency (EMA) recommended suspension of all ranitidine-containing medicines in the European Union (EU) due to the presence of N-nitrosodimethylamine (NDMA) impurities, which were considered to be carcinogenic. The aim of this study was to investigate the impact of regulatory intervention on use patterns of ranitidine-containing medicines and their therapeutic alternatives. Objectives: The aim was to study drug utilisation patterns of ranitidine and report discernible trends in treatment discontinuation and switching to alternative medications. Methods: This retrospective, population-based cohort study was conducted using primary care records from six European countries between 2017 and 2023. To explore drug utilisation patterns, we calculated (1) incident use of ranitidine, other H2RAs, and other alternative drugs for the treatment of gastric ulcer and/or gastric bleeding; (2) ranitidine discontinuation; and (3) switching from ranitidine to alternative drugs (H2RAs, proton-pump inhibitors [PPIs], and other medicinal products for acid-related disorders). Results: During the study period, 385,273 new ranitidine users were observed, with most users being female and aged 18–74 years. Ranitidine was the most commonly prescribed H2RA in the pre-referral period (September 2017–August 2019), with incidence rates between 0.8 and 9.0/1000 person years (PY). A steep decline to 0.3–3.8/1000 PY was observed in the referral period (September 2019–March 2020), eventually dropping to 0.0–0.4/1000 PY in the post-referral period (April 2020–March 2022). Switching from ranitidine to alternative drugs increased in the post-referral period, with the majority of patients switching to PPIs. Discontinuation of ranitidine use ranged from 270 to 380/1000 users in 2017 and decreased over time. Conclusions:Ranitidine was commonly used prior to referral, but it was subsequently discontinued and replaced primarily with PPIs.</p