Affirmative action and effort choice: An experimental investigation (WIDER Working Paper 2016/54)

We study the effect of affirmative action on effort in an experiment conducted in high schools in socioeconomically disadvantaged areas in Queensland, Australia. All participating schools have a large representation of indigenous Australians, a population group that is frequently targeted by affirmative action. Our participants perform a simple real-effort task in a competitive setting. Those ranked in the top third receive a high piece-rate payment and all the others receive a low payment. We introduce affirmative action by providing the lowest (bottom third) performers with a positive handicap increasing their chances to achieve the high payment target. Our findings show that the policy increases effort of those that it aims to favour, without discouraging effort of those who are indirectly penalized by affirmative action

Stakes are High: Essays on Brazil and the Future of the Global Internet

This workbook seeks to provide some background to the Global Meeting on the Future of Internet Governance (NETmundial) scheduled for April 23rd and 24th 2014 in São Paulo, Brazil. It is designed to help outline the internet policy issues that are at stake and will be discussed at NETmundial, as well as background on internet policy in Brazil. The workbook includes essays on the history of the NETmundial meeting and the Marco Civil process in Brazil; some background on the environment in Germany—with particular attention to the link between the meeting and the Snowden case; questions of legitimacy surrounding open processes for lawmaking; and comments on the material presented to the organizing committee by official and unofficial commenters. This workbook was produced as a part of the Internet Policy Observatory, a program at the Center for Global Communication Studies, the Annenberg School for Communication at the University of Pennsylvania. It was edited and curated by a steering committee including Ellery Roberts Biddle of Global Voices, Ronaldo Lemos of the Rio Institute for Technology and Society, and Monroe Price of the Annenberg School for Communication. They were assisted by Alexandra Esenler, Laura Schwartz-Henderson, and Briar Smith

Improvement of the impact resistance of natural fiber–reinforced polypropylene composites through hybridization

Polypropylene (PP) hybrid composites were prepared by the combination of naturalreinforcements and poly(ethylene terephthalate) (PET) fibers. Wood, flax, and sugarpalm fibers were used to increase stiffness and strength, while PET fibers served toimprove impact resistance. Interfacial adhesion was increased by using a maleated PP(MAPP) coupling agent. The hybrid composites containing 20 wt% of the naturalfibers were homogenized in a twin-screw compounder and then injection moldedinto standard tensile specimens. The amount of PET fibers was changed from 0 to40 wt% in the composites. Tensile and impact testing, acoustic emission measure-ments, and scanning electron microscopy (SEM) were used for the characterizationof the composites as well as to follow deformation and failure processes. The resultsproved that the concept of using PET fibers to improve impact resistance works withall natural fibers. Local deformations, the debonding or pullout of the PET fibers, initi-ate the plastic deformation of the matrix, which consumes considerable energy. Thefracture of PET fibers might also contribute to energy absorption. The type of naturalfiber does not influence the effect; the amount of PET fibers determines fractureresistance. The improvement of interfacial adhesion by coupling increases strengthand slightly improves impact resistance. The overall properties of the hybrid compos-ites prepared are acceptable, sufficiently large stiffness and impact resistance beingachieved for a large number of structural application

6-Sulfatoxymelatonin predicts treatment response to fluoxetine in major depressive disorder

Background: To date, no biomarker has been able to predict antidepressant response at an early blockade of norepinephrine or serotonin uptake. The transient nocturnal increase in plasma melatonin levels is upregulated by blocking these uptakes. The aim of this study was to test whether fluoxetine increase in urinary 6-sulfatoxymelatonin (aMT6s) is an indicator of serotonin uptake blockade. Methods: A total of 20 women (35–45 years of age) recruited from the community had a diagnosis of major depressive disorder confirmed by the Structured Clinical Interview for DSM-IV. Depressive symptoms were evaluated by the Beck Depression Inventory (BDI). Participants were instructed to take 20 mg of fluoxetine every morning. Every 4 weeks, the dose could be increased by 20 mg until symptom remission. The concentration of aMT6s was evaluated in overnight urine samples collected 1 day before and 1 day after the first fluoxetine dose. Results: An increase in aMT6s correlated to a decrease in BDI score evaluated on day 45 (ρ=−0.67, p = 0.024) was observed. Conclusions: Nocturnal increase in urinary aMT6s after the first day of medication use links the early mechanism of action of fluoxetine to its clinical output 45 days later. Thus, the relationship between urinary aMT6s excretion 1 day before/1 day after is a biomarker for predicting clinical output earlier, reducing illness burden and health care costs

Matrix metalloproteinase gene polymorphisms and susceptibility to systemic sclerosis

The major pathological hallmark of the systemic sclerosis (SSc) is skin and internal organ fibrosis, which results from normal tissue architecture alterations and extracellular matrix (ECM) protein deposition. ECM components are degraded by matrix metalloproteinases (MMP). Promoter region polymorphisms in MMP genes may influence gene expression, resulting in an imbalance between ECM protein production and degradation. Here, we analyzed MMP1 -1607 1G/2G (rs1799750), MMP3 -1171 5A/6A (rs3025058), and MMP9 -1562 C/T (rs3918242) polymorphisms in relation to susceptibility to SSc and its clinical features. The patient group included 98 individuals with longstanding or recently diagnosed disease, meeting the American College of Rheumatology or LeRoy and Medsger criteria for SSc; the control group included 100 healthy blood donors. All participants were of European descent. Genotyping was performed by polymerase chain reaction followed by restriction digestion. Genotype and allele frequencies of MMP polymorphisms were similar between the two groups. In secondary analyses, significantly higher frequency of 1G/2G genotype from MMP1 polymorphism was observed for patients testing positive for antinuclear autoantibodies (P = 0.007), while 1G/1G genotype was associated with interstitial lung disease development (P = 0.018). The 6A/6A genotype from MMP3 polymorphism was absent in patients with calcinosis (P = 0.011), while the MMP3 5A/5A genotype correlated with the presence of anti-topoisomerase I antibodies (P = 0.009) and reduced diffusing capacity for carbon monoxide (P = 0.024). These results suggest that MMP polymorphisms are not associated with SSc susceptibility, although MMP1 and MMP3 variants are associated with specific SSc clinical and laboratory features

Deposition of lignin in four species of Saccharum

We used primers designed on conserved gene regions of several species to isolate the most expressed genes of the lignin pathway in four Saccharum species. S. officinarum and S. barberi have more sucrose in the culms than S. spontaneum and S. robustum, but less polysaccharides and lignin in the cell wall. S. spontaneum, and S. robustum had the lowest S/G ratio and a lower rate of saccharification in mature internodes. Surprisingly, except for CAD, 4CL, and CCoAOMT for which we found three, two, and two genes, respectively, only one gene was found for the other enzymes and their sequences were highly similar among the species. S. spontaneum had the highest expression for most genes. CCR and CCoAOMT B presented the highest expression; 4CL and F5H showed increased expression in mature tissues; C3H and CCR had higher expression in S. spontaneum, and one of the CADs isolated (CAD B) had higher expression in S. officinarum. The similarity among the most expressed genes isolated from these species was unexpected and indicated that lignin biosynthesis is conserved in Saccharum including commercial varieties Thus the lignin biosynthesis control in sugarcane may be only fully understood with the knowledge of the promotor region of each gene9CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPsem informaçãosem informação2014/25994-1; 2008/58035-

Frontline bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in transplantation-ineligible patients with newly diagnosed mantle cell lymphoma: final overall survival results of a randomised, open-label, phase 3 study

In the LYM-3002 study, the efficacy and safety of frontline bortezomib plus rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were compared in transplant-ineligible patients with untreated, newly diagnosed, mantle cell lymphoma. We report the final overall survival and safety outcomes for patients in the long-term follow-up phase after the primary progression-free-survival endpoint was met.LYM-3002 was a randomised, open-label, phase 3 study done at 128 clinical centres in 28 countries in Asia, Europe, North America, and South America. Adult patients with confirmed stage II-IV previously untreated mantle cell lymphoma, Eastern Cooperative Oncology Group performance status score of 2 or less, who were ineligible for bone marrow transplantation, were randomly assigned (1:1) to receive six or eight 21-day cycles of VR-CAP (intravenous rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and bortezomib 1·3 mg/m2, plus oral prednisone 100 mg/m2) or R-CHOP (intravenous vincristine 1·4 mg/m2 [2 mg maximum], rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, and doxorubicin 50 mg/m2, plus oral prednisone 100 mg/m2). Randomisation was done according to a computer-generated randomisation schedule prepared by the sponsor; permuted blocks central randomisation was used (block size of 4), and was stratified by International Prognostic Index score and disease stage at diagnosis. The primary endpoint of this final analysis was overall survival, which was analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00722137, and is closed to new participants with follow-up completed.Between May 22, 2008, and Dec 5, 2011, 487 patients were enrolled and randomly assigned. 268 patients (140 in the VR-CAP group and 128 in the R-CHOP group) were included in the follow-up analysis, which included patients with data available after the primary analysis clinical cutoff date of Dec 2, 2013. After median follow-up of 82·0 months (IQR 74·1-94·2), median overall survival was significantly longer in the VR-CAP group than in the R-CHOP group (90·7 months [95% CI 71·4 to not estimable] vs 55·7 months [47·2 to 68·9]; hazard ratio 0·66 [95% CI 0·51-0·85]; p=0·001). Three new adverse events were reported since the primary analysis cutoff (one each of grade 4 lung adenocarcinoma and grade 4 gastric cancer in the VR-CAP group, and one case of grade 2 pneumonia in the R-CHOP group). 103 (42%) of 243 patients in the VR-CAP group, and 138 (57%) of 244 in the R-CHOP group died; the most common cause of death was progressive disease.Compared with R-CHOP, VR-CAP was associated with significantly longer survival, and had a manageable and expected safety profile. Our results support further assessment of VR-CAP in patients with previously untreated mantle cell lymphoma.Janssen Research & Development

Finerenone in Predominantly Advanced CKD and Type 2 Diabetes With or Without Sodium-Glucose Cotransporter-2 Inhibitor Therapy

INTRODUCTION: FIDELIO-DKD (FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease) investigated the nonsteroidal, selective mineralocorticoid receptor (MR) antagonist finerenone in patients with CKD and type 2 diabetes (T2D). This analysis explores the impact of use of sodium-glucose cotransporter-2 inhibitor (SGLT-2i) on the treatment effect of finerenone. METHODS: Patients (N = 5674) with T2D, urine albumin-to-creatinine ratio (UACR) of 30 to 5000 mg/g and estimated glomerular filtration rate (eGFR) of 25 to <75 ml/min per 1.73 m(2) receiving optimized renin-angiotensin system (RAS) blockade were randomized to finerenone or placebo. Endpoints were change in UACR and a composite kidney outcome (time to kidney failure, sustained decrease in eGFR ≥40% from baseline, or renal death) and key secondary cardiovascular outcomes (time to cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) (ClinicalTrials.gov, NCT02540993). RESULTS: Of 5674 patients, 259 (4.6%) received an SGLT-2i at baseline. Reduction in UACR with finerenone was found with or without use of SGLT-2i at baseline, with ratio of least-squares means of 0.69 (95% CI = 0.66–0.71) and 0.75 (95% CI -= 0.62–0.90), respectively (P(interaction) = 0.31). Finerenone also significantly reduced the kidney and key secondary cardiovascular outcomes versus placebo; there was no clear difference in the results by SGLT-2i use at baseline (P(interaction) = 0.21 and 0.46, respectively) or at any time during the trial. Safety was balanced with or without SGLT-2i use at baseline, with fewer hyperkalemia events with finerenone in the SGLT-2i group (8.1% vs. 18.7% without). CONCLUSION: UACR improvement was observed with finerenone in patients with CKD and T2D already receiving SGLT-2is at baseline, and benefits on kidney and cardiovascular outcomes appear consistent irrespective of use of SGLT-2i

The eukaryotic linear motif resource ELM: 10 years and counting

The eukaryotic linear motif (ELM http://elm.eu.org) resource is a hub for collecting, classifying and curating information about short linear motifs (SLiMs). For >10 years, this resource has provided the scientific community with a freely accessible guide to the biology and function of linear motifs. The current version of ELM contains ∼200 different motif classes with over 2400 experimentally validated instances manually curated from >2000 scientific publications. Furthermore, detailed information about motif-mediated interactions has been annotated and made available in standard exchange formats. Where appropriate, links are provided to resources such as switches.elm.eu.org and KEGG pathways.Fil: Dinkel, Holder. European Molecular Biology Laboratory; AlemaniaFil: Van Roey, Kim. European Molecular Biology Laboratory; AlemaniaFil: Michael, Sushama. European Molecular Biology Laboratory; AlemaniaFil: Davey, Norman E.. University Of California ; Estados UnidosFil: Weatheritt, Robert J.. MRC. Laboratory of Molecular Biology; Estados UnidosFil: Born, Diana. Ruprecht-Karls-Universität; AlemaniaFil: Speck, Tobias. Ruprecht-Karls-Universität; AlemaniaFil: Kruger, Daniel. Ruprecht-Karls-Universität; AlemaniaFil: Grebnev, Gleb. University College Dublin; IrlandaFil: Kuban, Marta. Maria Sklodowska-Curie Memorial Cancer Center. Laboratory of Bioinformatics and Biostatistics; PoloniaFil: Strumillo, Marta. Maria Sklodowska-Curie Memorial Cancer Center. Laboratory of Bioinformatics and Biostatistics; PoloniaFil: Uyar, Bora. European Molecular Biology Laboratory; AlemaniaFil: Budd, Aidan. European Molecular Biology Laboratory; AlemaniaFil: Altenberg, Brigitte. European Molecular Biology Laboratory; AlemaniaFil: Seiler, Markus. European Molecular Biology Laboratory; AlemaniaFil: Chemes, Lucia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Glavina, Juliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Sánchez Miguel, Ignacio Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Diella, Francesca. European Molecular Biology Laboratory; AlemaniaFil: Gibson, Toby J. European Molecular Biology Laboratory; Alemani

SARSCOVIDB : a new platform for the analysis of the molecular impact of SARS-CoV-2 viral infection

The COVID-19 pandemic caused by the new coronavirus (SARS-CoV-2) has become a global emergency issue for public health. This threat has led to an acceleration in related research and, consequently, an unprecedented volume of clinical and experimental data that include changes in gene expression resulting from infection. The SARS-CoV-2 infection database (SARSCOVIDB: https://sarscovidb.org/) was created to mitigate the dificulties related to this scenario. The SARSCOVIDB is an online platform that aims to integrate all differential gene expression data, at messenger RNA and protein levels, helping to speed up analysis and research on the molecular impact of COVID-19. The database can be searched from different experimental perspectives and presents all related information from published data, such as viral strains, hosts, methodological approaches (proteomics or transcriptomics), genes/proteins, and samples (clinical or experimental). All information was taken from 24 articles related to analyses of differential gene expression out of 5,554 COVID-19/SARS-CoV-2-related articles published so far. The database features 12,535 genes whose expression has been identified as altered due to SARS-CoV-2 infection. Thus, the SARSCOVIDB is a new resource to support the health workers and the scientific community in understanding the pathogenesis and molecular impact caused by SARS-CoV-2