Special issue on recent advances in lot sizing

Production planning aims to efficiently plan the production activities as well as the acquisition of the raw materials and resources required to transform raw materials into finished products, in order to meet customer demand in the most economical way possible. The decisions to be made include, but are not limited to, production lot sizes, setup decisions, work force levels and sequencing of production runs, while the ultimate aim is to determine the optimal timing and level of production

The complete genome sequence of Chromobacterium violaceum reveals remarkable and exploitable bacterial adaptability

Chromobacterium violaceum is one of millions of species of free-living microorganisms that populate the soil and water in the extant areas of tropical biodiversity around the world. Its complete genome sequence reveals (i) extensive alternative pathways for energy generation, (ii) ≈500 ORFs for transport-related proteins, (iii) complex and extensive systems for stress adaptation and motility, and (iv) wide-spread utilization of quorum sensing for control of inducible systems, all of which underpin the versatility and adaptability of the organism. The genome also contains extensive but incomplete arrays of ORFs coding for proteins associated with mammalian pathogenicity, possibly involved in the occasional but often fatal cases of human C. violaceum infection. There is, in addition, a series of previously unknown but important enzymes and secondary metabolites including paraquat-inducible proteins, drug and heavy-metal-resistance proteins, multiple chitinases, and proteins for the detoxification of xenobiotics that may have biotechnological applications

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

<it>IL1B</it>, <it>IL4R</it>, <it>IL12RB1</it> and <it>TNF</it> gene polymorphisms are associated with <it>Plasmodium vivax</it> malaria in Brazil

Abstract Background Malaria is among the most prevalent parasitic diseases worldwide. In Brazil, malaria is concentrated in the northern region, where Plasmodium vivax accounts for 85% disease incidence. The role of genetic factors in host immune system conferring resistance/susceptibility against P. vivax infections is still poorly understood. Methods The present study investigates the influence of polymorphisms in 18 genes related to the immune system in patients with malaria caused by P. vivax. A total of 263 healthy individuals (control group) and 216 individuals infected by P. vivax (malaria group) were genotyped for 33 single nucleotide polymorphisms (SNPs) in IL1B, IL2, IL4, IL4R, IL6, IL8, IL10, IL12A, IL12B, IL12RB1, SP110, TNF, TNFRSF1A, IFNG, IFNGR1, VDR, PTPN22 and P2X7 genes. All subjects were genotyped with 48 ancestry informative insertion-deletion polymorphisms to determine the proportion of African, European and Amerindian ancestry. Only 13 SNPs in 10 genes with differences lower than 20% between cases and controls in a Poisson Regression model with age as covariate were further investigated with a structured population association test. Results The IL1B gene -5839C > T and IL4R 1902A > G polymorphisms and IL12RB1 -1094A/-641C and TNF -1031 T/-863A/-857 T/-308 G/-238 G haplotypes were associated with malaria susceptibility after population structure correction (p = 0.04, p = 0.02, p = 0.01 and p = 0.01, respectively). Conclusion Plasmodium vivax malaria pathophysiology is still poorly understood. The present findings reinforce and increase our understanding about the role of the immune system in malaria susceptibility.</p

Isolation of Saccharomyces cerevisiae strains producing higher levels of flavoring compounds for production of ??cacha?a?? the Brazilian sugarcane spirit.

In Brazil, spontaneous fermentation and open vessels are still used to produce cachac?a (the Brazilian sugarcane spirit) and this fermentation is characterized by mixed cultures with continuous succession of yeast species. This work shows the development of a methodology for isolation of yeasts, particularly Saccharomyces cerevisiae, used in the production of cachac?a. According to the proposed strategy, the strains were selected for their ability to adapt to stress conditions encountered during fermentation of the sugarcane juice such as high sucrose concentration; high temperatures and high alcohol concentration; for their capacity to flocculate; and for their higher fermentative ability. For strains with such characteristics, specific procedures were employed to select for 5,5,5-trifluoro-dl-leucine (TFL) and cerulenin-resistant strains, since these characteristics are related to a higher capacity of production of the flavoring compounds isoamyl alcohol and caproic acid, respectively. The effectiveness of such a selection strategy was documented. Taken together, the results obtained present the development of a new strategy to isolate yeast strains with appropriated characteristics to be used in the cachac?a industry. Moreover, the results obtained offer an explanation for the great variability in terms of chemical composition found in products obtained even in a single distillery

SLCO1A2, SLCO1B1 and SLCO2B1 polymorphisms influences chloroquine and primaquine treatment in Plasmodium vivax malaria

Financial support was provided by Conselho Nacional de Desenvolvimento Cient´ıfico e Tecnologico (CNPq, Brazil)Universidade Federal do Rio Grande do Sul. Departamento de Genética. Porto Alegre, RS, Brazil.Universidade Federal do Rio Grande do Sul. Departamento de Genética. Porto Alegre, RS, Brazil.Universidade Federal do Para. Laboratório de Microbiologia e Imunologia. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Programa de Ensaios Clínicos em Malária. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Programa de Ensaios Clínicos em Malária. Ananindeua, PA, Brasil.Universidade Federal do Pará. Laboratório de Genética Humana e Médica. Belém, PA, Brazil.Universidade Federal do Pará. Laboratório de Genética Humana e Médica. Belém, PA, Brazil.Hospital de Clínicas de Porto Alegre. Unidade de Bioestatística. Grupo de Pesquisa e Pós Graduação. Porto Alegre, RS, Brazil.Universidade Federal do Rio Grande do Sul. Departamento de Genética. Porto Alegre, RS, Brazil.Aim: The association of transporters gene polymorphisms with chloroquine/primaquine malaria treatment response was investigated in a Brazilian population. Patients & methods: Totally, 164 Plasmodium vivax malaria infected patients were included. Generalized estimating equations were performed to determine gene influences on parasitemia and/or gametocytemia clearance over treatment time. Results: Significant interaction between SLCO2B1 genotypes and treatment over time for parasitemia clearance rate on day 2 were observed (p FDR = 0.002). SLCO1A2 and SLCO1B1 gene treatment over time interactions were associated with gametocytemia clearance rate (p FDR = 0.018 and p FDR = 0.024). ABCB1, ABCC4 and SLCO1B3 were not associated with treatment response. Conclusion: The present work presents the first pharmacogenetic report of an association between chloroquine/primaquine responses with OATP transporters

The effect of SNPs in CYP450 in chloroquine/primaquine Plasmodium vivax malaria treatment

The authors thank the financial support provided by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil)Universidade Federal do Rio Grande do Sul. Departamento de Genética. Porto Alegre, RS, Brazil.Universidade Federal do Rio Grande do Sul. Departamento de Genética. Porto Alegre, RS, Brazil.Universidade Federal do Pará. Laboratório de Microbiologia e Imunologia. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Universidade Federal do Pará. Laboratório de Genética Humana e Médica. Belém, PA, Brazil.Universidade Federal do Pará. Laboratório de Genética Humana e Médica. Belém, PA, Brazil.Hospital de Clínicas de Porto Alegre.Grupo de Pesquisa e Pós Graduação. Unidade de Bioestatística. Porto Alegre, RS, Brazil.Universidade Federal do Rio Grande do Sul. Departamento de Genética. Porto Alegre, RS, Brazil.Background: Chloroquine/primaquine is the current therapy to eliminate Plasmodium vivax infection in the Amazon region. Aims: This study investigates CYP1A2, CYP2C8, CYP2C9, CYP3A4 and CYP3A5 genetic polymorphisms influence on cloroquine/primaquine treatment. Patients & methods: Generalized estimating equations analyses were performed to determine the genetic influence in parasitemia and/or gametocytemia clearance over treatment time in 164 patients. Results: An effect of CYP2C8 low-activity alleles on treatment was observed (p = 0.01). From baseline to first day of treatment, wild-type individuals achieved greater reduction of gametocytes than low-activity allele carriers. CYP2C9 and CYP3A5 genes showed a trend for gametocytemia and parasitemia clearance rates. Conclusion: Future studies should be performed to access the extent of CYP2C8, CYP2C9 and CYP3A5 gene polymorphisms influence on cloroquine/primaquine treatment

SLCO1A2, SLCO1B1

Financial support was provided by Conselho Nacional de Desenvolvimento Cient´ıfico e Tecnologico (CNPq, Brazil)Universidade Federal do Rio Grande do Sul. Departamento de Genética. Porto Alegre, RS, Brazil.Universidade Federal do Rio Grande do Sul. Departamento de Genética. Porto Alegre, RS, Brazil.Universidade Federal do Para. Laboratório de Microbiologia e Imunologia. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Programa de Ensaios Clínicos em Malária. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Programa de Ensaios Clínicos em Malária. Ananindeua, PA, Brasil.Universidade Federal do Pará. Laboratório de Genética Humana e Médica. Belém, PA, Brazil.Universidade Federal do Pará. Laboratório de Genética Humana e Médica. Belém, PA, Brazil.Hospital de Clínicas de Porto Alegre. Unidade de Bioestatística. Grupo de Pesquisa e Pós Graduação. Porto Alegre, RS, Brazil.Universidade Federal do Rio Grande do Sul. Departamento de Genética. Porto Alegre, RS, Brazil.Aim: The association of transporters gene polymorphisms with chloroquine/primaquine malaria treatment response was investigated in a Brazilian population. Patients & methods: Totally, 164 Plasmodium vivax malaria infected patients were included. Generalized estimating equations were performed to determine gene influences on parasitemia and/or gametocytemia clearance over treatment time. Results: Significant interaction between SLCO2B1 genotypes and treatment over time for parasitemia clearance rate on day 2 were observed (p FDR = 0.002). SLCO1A2 and SLCO1B1 gene treatment over time interactions were associated with gametocytemia clearance rate (p FDR = 0.018 and p FDR = 0.024). ABCB1, ABCC4 and SLCO1B3 were not associated with treatment response. Conclusion: The present work presents the first pharmacogenetic report of an association between chloroquine/primaquine responses with OATP transporters