The gathering firestorm in southern Amazonia.

Wildfires, exacerbated by extreme weather events and land use, threaten to change the Amazon from a net carbon sink to a net carbon source. Here, we develop and apply a coupled ecosystem-fire model to quantify how greenhouse gas-driven drying and warming would affect wildfires and associated CO2 emissions in the southern Brazilian Amazon. Regional climate projections suggest that Amazon fire regimes will intensify under both low- and high-emission scenarios. Our results indicate that projected climatic changes will double the area burned by wildfires, affecting up to 16% of the region's forests by 2050. Although these fires could emit as much as 17.0 Pg of CO2 equivalent to the atmosphere, avoiding new deforestation could cut total net fire emissions in half and help prevent fires from escaping into protected areas and indigenous lands. Aggressive efforts to eliminate ignition sources and suppress wildfires will be critical to conserve southern Amazon forests

Characterization of antioxidant olive oil biophenols by spectroscopic methods

Olive oil contains numerous phenolic components with well-recognized health-beneficial activity. The major phenolic compounds present in olives and virgin olive oil-hydroxytyrosol, oleuropein and the oleuropein aglycones 3,4-DHPEA-EA and 3,4-DHPEA-EDA-as well as some of their metabolites were studied in the present work, regarding their main structural preferences. Vibrational spectroscopy (Raman) coupled to theoretical methods were used, aiming at fully characterizing the systems and therefore enabling their quick and reliable identification in food samples

Developing a gender-based approach to chronic conditions and women's health: A qualitative investigation of communitydwelling women and service provider perspectives

© 2015 DiGiacomo et al. Background: Chronic conditions contribute to over 70 % of Australia's total disease burden, and this is set to increase to 80 % by 2020. Women's greater longevity means that they are more likely than men to live with disability and have unique health concerns related to their gender based roles in society. Cultural and social issues can impact on women's health and are important to consider in health services planning and research. In this study, we aimed to identify barriers and facilitators to providing a gender-based approach to chronic conditions and women's health in an eastern metropolitan region of Australia. Methods: Focus groups were used to engage both community-dwelling women who had chronic conditions and relevant professional stakeholders in the target area. Recorded proceedings underwent thematic analysis. Results: Five focus groups were conducted with professional stakeholders and women community members in February and March 2014. Resultant themes included: women's disempowerment through interactions with health systems; social and economic constraints and caregiving roles act to exclude women from participating in self-care and society; and empowerment can be achieved through integrated models of care that facilitate voice and enable communication and engagement. Conclusions: This study underscores the importance of including perspectives of sex and gender in health care services planning. Tailoring services to socio-demographic and cultural groups is critical in promoting access to health care services. Unique epidemiological trends, particularly the ageing of women and new migrant groups, require particular attention

Selection bias: neighbourhood controls and controls selected from those presenting to a Health Unit in a case control study of efficacy of BCG revaccination.

BACKGROUND: In most case control studies the hardest decision is the choice of the control group, as in the ideal control group the proportion exposed is the same as in the population that produced the cases. METHODS: A comparison of two control groups in a case control study of the efficacy of BCG revaccination. One group was selected from subjects presenting to the heath unit the case attended for routine prevention and care; the second group was selected from the neighbourhood of cases. All Health Units from which controls were selected offered BCG revaccination. Efficacy estimated in a randomized control trial of BCG revaccination was used to establish that the neighbourhood control group was the one that gave unbiased results. RESULTS: The proportion of controls with scars indicating BCG revaccination was higher among the control group selected from Health Unit attenders than among neighbourhood controls. This excess was not removed after control for social variables and history of exposure to tuberculosis, and appears to have resulted from the fact that people attending the Health Unit were more likely to have been revaccinated than neighbourhood controls, although we can not exclude an effect of other unmeasured variables. CONCLUSION: In this study, controls selected from people presenting to a Health Unit overrepresented exposure to BCG revaccination. Had the results from the HU attenders control group been accepted this would have resulted in overestimation of vaccine efficacy. When the exposure of interest is offered in a health facility, selection of controls from attenders at the facility may result in over representation of exposure in controls and selection bias

Leveraging vectored vaccine candidates manufacturing to GMP compatible bioprocesse

Background Vectored vaccines are very efficient in the in vivo delivery of antigens either in the form of antigen protein and peptides or genetic material. The bioprocess of vectored vaccines poses however several challenge since the viral particles to be effective must maintain their infectivity. Lentiviral and adenoviral vectors are among the particles more used in the treatment of cancer diseases modulating the immune system. Both viral vectors are currently produced in transient upstream process. While the adenoviral vectors are produced at high titers the lentiviral vector upstream process still requires further improvement. The non-lytic nature of lentivirus enables the design of stable cell lines which may improve its yields through perfusion and longer term productions, reducing costs. The application of novel methods for the downstream processing such as continuous purification will contribute to increase the yield and lower the overall cost of the manufacturing processes. Experimental approach At the upstream process, many of the challenges lentiviral bioproducts present in its manufacturing are related to the apoptosis-leading cytotoxicity of some of the vector components. Supported on our long track experience and enabling tools developed for gammaretrovirus manufacturing, we undertook the challenge of establishing a constitutive stable lentiviral producer cell line. To address this challenge we proposed to eliminate or reduce the cytotoxicity of the lentiviral vector expression components. At the downstream process lentiviral vectors face the challenges common to retroviridae family of vectors namely short half-lives at room temperature, sensitivity to pH variations and salt concentrations, and shear stress. The purification strategy developed was designed to be based on disposable and easily scalable technologies. A final concentration achieving 108 TU mL-1 was targeted since the concentration step itself allows to reduce the burden on process and improve the transduction efficiency. To address the high doses requirements we will report an improved oncolytic adenovirus purification process for phase I and II clinical trials and present a case on the use of Polysorb 20 as a replacement for Triton X-100 during cell lysis. Product recovery, potency, purity and the effect of manufacturing holding points will be discussed. Results and discussion A lentiviral producer cell line constitutively producing titers above 106 TU.mL-1.day-1 was established. The cell line showed to be stable, consistently maintaining vector productivity over one month in the absence of antibiotics. At the bioreaction process it was possible to maintain the cells continuously producing over 10 days. At downstream we implemented scalable protocols for lentiviral and adenoviral vectors that is easy to transfer to GMP environment, combining microfiltration, anion-exchange, and ultrafiltration membranes technologies toward maximization of infectious virus recovery, allowing generation of clinical-grade viral vectors without the need for cleaning validation in a cost-effective manner. Herein we will present and discuss the challenges on the biomanufacturing of lentiviral as well as adenoviral virus, the strategies and novel technologies to be adopted in order to enable a faster development of novel vectored vaccine candidates focusing on several case studies, supported by process technology innovation

Well-being and quality of life in a sample of bakers and confectioners from the central region

info:eu-repo/semantics/publishedVersio

EULAR COVID-19 registry: lessons learnt and future considerations.

Future disease outbreaks of epidemic proportion are inevitable. Advance planning and preparation is essential to mitigate future public health risks; the WHO emphasises the importance of in-depth evaluation of response to and lessons learnt from a national/international pandemic.1 Research is critical to an informed, evidence-based response, therefore establishing pandemic research study protocols, systems to manage and report data, and rapid response teams are considered key to well-prepared, accelerated research in public health emergencies.2 Establishing international data collection registries poses many challenges, which are only amplified in the urgent nature of a global pandemic. The aim of this manuscript is to reflect on the successes and challenges of the European Alliance of Associations for Rheumatology (EULAR) COVID-19 registry3 to better understand how the rheumatology community (and other disease-specific communities) can be better prepared for rapid response research in the future. In particular, we consider the successes and challenges of the registry, what can be learnt from this experience, and what procedures and resources should be established and strengthened now in preparation for future pandemics

Intermediate expression of CCRL1 reveals novel subpopulations of medullary thymic epithelial cells that emerge in the postnatal thymus.

Cortical and medullary thymic epithelial cells (cTECs and mTECs, respectively) provide inductive microenvironments for T-cell development and selection. The differentiation pathway of cTEC/mTEC lineages downstream of common bipotent progenitors at discrete stages of development remains unresolved. Using IL-7/CCRL1 dual reporter mice that identify specialized TEC subsets, we show that the stepwise acquisition of chemokine (C-C motif) receptor-like 1 (CCRL1) is a late determinant of cTEC differentiation. Although cTECs expressing high CCRL1 levels (CCRL1(hi) ) develop normally in immunocompetent and Rag2(-/-) thymi, their differentiation is partially blocked in Rag2(-/-) Il2rg(-/-) counterparts. These results unravel a novel checkpoint in cTEC maturation that is regulated by the cross-talk between TECs and immature thymocytes. Additionally, we identify new Ulex europaeus agglutinin 1 (UEA)(+) mTEC subtypes expressing intermediate CCRL1 levels (CCRL1(int) ) that conspicuously emerge in the postnatal thymus and differentially express Tnfrsf11a, Ccl21, and Aire. While rare in fetal and in Rag2(-/-) thymi, CCRL1(int) mTECs are restored in Rag2(-/-) Marilyn TCR-Tg mice, indicating that the appearance of postnatal-restricted mTECs is closely linked with T-cell selection. Our findings suggest that alternative temporally restricted routes of new mTEC differentiation contribute to the establishment of the medullary niche in the postnatal thymus.We thank James Di Santo, Jocelyne Demengeot, and Thomas Boehm for Rag2−/−Il2rg−/−, CCRL1-reporter, and Marilyn-Rag2−/− mice, respectively. We thank Dr. Catarina Leit˜ao for critical reading of the manuscript and technical assistance. We thank FEDER funds through the Operational Competitiveness Programme – COMPETE and by National Funds through Fundaçao para a Ciência e a Tecnologia (FCT) under the project PTDC/SAU-IMU/117057/2010 funded this work. N.L.A., A.R.R.,C.M., and P.M.R. are supported by FCT Investigator program and PhD fellowships

Hydrogel-Assisted Antisense LNA Gapmer Delivery for In Situ Gene Silencing in Spinal Cord Injury

After spinal cord injury (SCI), nerve regeneration is severely hampered due to the establishment of a highly inhibitory microenvironment at the injury site, through the contribution of multiple factors. The potential of antisense oligonucleotides (AONs) to modify gene expression at different levels, allowing the regulation of cell survival and cell function, together with the availability of chemically modified nucleic acids with favorable biopharmaceutical properties, make AONs an attractive tool for novel SCI therapy developments. In this work, we explored the potential of locked nucleic acid (LNA)-modified AON gapmers in combination with a fibrin hydrogel bridging material to induce gene silencing in situ at a SCI lesion site. LNA gapmers were effectively developed against two promising gene targets aiming at enhancing axonal regeneration—RhoA and GSK3ß. The fibrin-matrix-assisted AON delivery system mediated potent RNA knockdown in vitro in a dorsal root ganglion explant culture system and in vivo at a SCI lesion site, achieving around 75% downregulation 5 days after hydrogel injection. Our results show that local implantation of a AON-gapmer-loaded hydrogel matrix mediated efficient gene silencing in the lesioned spinal cord and is an innovative platform that can potentially combine gene regulation with regenerative permissive substrates aiming at SCI therapeutics and nerve regeneration.This work was supported by Fundação para a Ciência e a Tecnologia ( FCT , Portugal) in the framework of the Harvard-Portugal Medical School Program ( HMSP-ICT/0020/2010 ); Project NORTE-01-0145-FEDER-000008 , supported by the Norte Portugal Regional Operational Programme (NORTE 2020) , under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) ; Fundo Europeu de Desenvolvimento Regional funds through COMPETE 2020 - Operational Program for Competitiveness and Internationalization (POCI) , Portugal 2020; by Portuguese funds through FCT/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project “Institute for Research and Innovation in Health Sciences” ( POCI-01-0145-FEDER-007274 ); Marie Curie Actions of the European Community’s 7th Framework Program ( PIEF-GA-2011-300485 to P.M.D.M.); Santa Casa da Misericordia de Lisboa – Prémio Neurociências Mello e Castro , and FCT fellowship SFRH/BPD/108738/2015 (to P.M.D.M). Funding for open access charge: Project NORTE-01-0145-FEDER-000012 , financed by Norte Portugal Regional Operational Programme (NORTE 2020) , under the PORTUGAL 2020 Partnership Agreement, through the ERDF . We would like to acknowledge the support from Paula Magalhães and Tânia Meireles from the i3S Cell Culture and Genotyping Core Facility in real-time PCR experiments