276 research outputs found
ANÁLISE PRELIMINAR DAS POLÍTICAS E LEIS AMBIENTAIS E URBANÍSTICAS E SUAS REPERCUSSÕES SOBRE ÁREAS PROTEGIDAS URBANAS
Neste artigo são analisadas as principais políticas e legislações ambientais e urbanísticas brasileiras que afetam direta ou indiretamente áreas verdes urbanas. Foi identificado que as políticas públicas como as ambientais e urbanísticas não influenciam diretamente as áreas verdes urbanas, mas sim, leis regulamentadoras e instrumentos como o zoneamento, a criação de unidades de conservação e o planejamento urbano como estabelecido pelo Plano Diretor
Multi-state open robust design applied to opportunistic data reveals dynamics of wide-ranging taxa: The sperm whale case.
© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Boys, R. M., Oliveira, C., Perez-Jorgeo, S., Prieto, R., Steiner, L., & Silva, M. A. Multi-state open robust design applied to opportunistic data reveals dynamics of wide-ranging taxa: The sperm whale case. Ecosphere, 10(3), (2019):e02610, doi:10.1002/ecs2.2610.Capture–mark–recapture methods have been extensively used to estimate abundance, demography, and life history parameters of populations of several taxa. However, the high mobility of many species means that dedicated surveys are logistically complicated and expensive. Use of opportunistic data may be an alternative, if modeling takes into account the inevitable heterogeneity in capture probability from imperfect detection and incomplete sampling, which can produce significant bias in parameter estimates. Here, we compare covariate‐based open Jolly‐Seber models (POPAN) and multi‐state open robust design (MSORD) models to estimate demographic parameters of the sperm whale population summering in the Azores, from photo‐identification data collected opportunistically by whale‐watching operators and researchers. The structure of the MSORD also allows for extra information to be obtained, estimating temporary emigration and improving precision of estimated parameters. Estimates of survival from both POPAN and MSORD were high, constant, and very similar. The POPAN model, which partially accounted for heterogeneity in capture probabilities, estimated an unbiased super‐population of ~1470 whales, with annual abundance showing a positive trend from 351 individuals (95% CI: 234–526) in 2010 to 718 (95% CI: 477–1082) in 2015. In contrast, estimates of abundance from MSORD models that explicitly incorporated imperfect detection due to temporary emigration were less biased, more precise, and showed no trend over years, from 275 individuals (95% CI: 188–404) in 2014 to 367 (95% CI: 248–542) in 2012. The MSORD estimated short residence time and an even‐flow temporary emigration, meaning that the probability of whales emigrating from and immigrating to the area was equal. Our results illustrate how failure to account for transience and temporary emigration can lead to biased estimates and trends in abundance, compromising our ability to detect true population changes. MSORD models should improve inferences of population dynamics, especially when capture probability is low and highly variable, due to wide‐ranging behavior of individuals or to non‐standardized sampling. Therefore, these models should provide less biased estimates and more accurate assessments of uncertainty that can inform management and conservation measures.We acknowledge IFAW for providing photo‐identification data from the early period of the study (1987–1993), Biosphere Expeditions and clients of Whale Watch Azores for making data collection possible. We thank Sara Magalhães, Tiago Sá, João Medeiros, Yves Cuenot, Pablo Chevallard Navarro, and numerous volunteers that over the years helped with data collection and organization of the photo‐identification catalogue. We are deeply grateful to Gary White, Bill Kendall, Jim Hines, James Nichols, Paul Conn, and Olivier Gimenez for offering guidance and advice on CMR modeling. We thank Jonathan Gordon for his comments on an earlier version of the manuscript. We are thankful to the three anonymous reviewers for providing very helpful comments.
This work was supported by Fundação para a Ciência e Tecnologia (FCT), Azores 2020 Operational Programme, and Fundo Regional da Ciência e Tecnologia (FRCT) through research projects FCT‐Exploratory project (IF/00943/2013/CP1199/CT0001), WATCH IT (Acores‐01‐0145‐FEDER‐000057), and MISTIC SEAS II (GA11.0661/2017/750679/SUB/ENV.C2) co‐funded by FEDER, COMPETE, QREN, POPH, ESF, Portuguese Ministry for Science and Education, and EU‐DG/ENV. The Azores 2020 Operational Programme is funded by the community structural funds ERDF and ESF. We also acknowledge funds provided by FCT to MARE, through the strategic project UID/MAR/04292/2013. Rebecca M Boys is supported by an Estagiar L scholarship, Cláudia Oliveira by a research assistant contract from WATCH IT and Mónica A Silva by an FCT‐Investigator contract (IF/00943/2013), and Rui Prieto by an FCT postdoctoral grant (SFRH/BPD/108007/2015).
Mónica A Silva conceptualized the project, acquired funding, administered, and supervised the project. Lisa Steiner, Cláudia Oliveira, Rebecca M Boys, and Mónica A Silva involved in data curation. Rebecca M Boys, Mónica A Silva, Sergi Pérez‐Jorge, and Cláudia Oliveira involved in formal analysis, investigation, and methodology. Rebecca M Boys preparation and visualization of the data. Rebecca M Boys, Mónica A Silva, Sergi Pérez‐Jorge, Rui Prieto wrote the original draft of the manuscript. Rebecca M Boys, Mónica A Silva, Rui Prieto, Sergi Pérez‐Jorge, Cláudia Oliveira, and Lisa Steiner wrote, reviewed, and edited the manuscript
A Nationwide Assessment of the Association of Smoking Bans and Cigarette Taxes With Hospitalizations for Acute Myocardial Infarction, Heart Failure, and Pneumonia
Multiple studies claim that public place smoking bans are associated with reductions in smoking-related hospitalization rates. No national study using complete hospitalization counts by area that accounts for contemporaneous controls including state cigarette taxes has been conducted. We examine the association between county-level smoking-related hospitalization rates and comprehensive smoking bans in 28 states from 2001 to 2008. Differences-in-differences analysis measures changes in hospitalization rates before versus after introducing bans in bars, restaurants, and workplaces, controlling for cigarette taxes, adjusting for local health and provider characteristics. Smoking bans were not associated with acute myocardial infarction or heart failure hospitalizations, but lowered pneumonia hospitalization rates for persons ages 60 to 74 years. Higher cigarette taxes were associated with lower heart failure hospitalizations for all ages and fewer pneumonia hospitalizations for adults aged 60 to 74. Previous studies may have overestimated the relation between smoking bans and hospitalizations and underestimated the effects of cigarette taxes
Cleavage efficiency of the intramembrane protease γ-secretase is reduced by the palmitoylation of a substrate's transmembrane domain
The intramembrane protease gamma-secretase has broad physiological functions, but also contributes to Notch-dependent tumors and Alzheimer's disease. While gamma-secretase cleaves numerous membrane proteins, only few nonsubstrates are known. Thus, a fundamental open question is how gamma-secretase distinguishes substrates from nonsubstrates and whether sequence-based features or post-translational modifications of membrane proteins contribute to substrate recognition. Using mass spectrometry-based proteomics, we identified several type I membrane proteins with short ectodomains that were inefficiently or not cleaved by gamma-secretase, including 'pituitary tumor-transforming gene 1-interacting protein' (PTTG1IP). To analyze the mechanism preventing cleavage of these putative nonsubstrates, we used the validated substrate FN14 as a backbone and replaced its transmembrane domain (TMD), where gamma-cleavage occurs, with the one of nonsubstrates. Surprisingly, some nonsubstrate TMDs were efficiently cleaved in the FN14 backbone, demonstrating that a cleavable TMD is necessary, but not sufficient for cleavage by gamma-secretase. Cleavage efficiencies varied by up to 200-fold. Other TMDs, including that of PTTG1IP, were still barely cleaved within the FN14 backbone. Pharmacological and mutational experiments revealed that the PTTG1IP TMD is palmitoylated, which prevented cleavage by gamma-secretase. We conclude that the TMD sequence of a membrane protein and its palmitoylation can be key factors determining substrate recognition and cleavage efficiency by gamma-secretase. The intramembrane protease gamma-secretase has broad physiological functions. However, a fundamental open question is how gamma-secretase distinguishes substrates from nonsubstrates and whether sequence-based features or post-translational modifications of membrane proteins contribute to substrate recognition. Using mass spectrometry-based proteomics and domain swap experiments, this study demonstrates that palmitoylation within the C-terminal half of a substrate's transmembrane domain constitutes a new mechanism that can suppress cleavage by gamma-secretase.imag
Functional analysis and transcriptional output of the Göttingen minipig genome
In the past decade the Göttingen minipig has gained increasing recognition as animal model in pharmaceutical and safety research because it recapitulates many aspects of human physiology and metabolism. Genome-based comparison of drug targets together with quantitative tissue expression analysis allows rational prediction of pharmacology and cross-reactivity of human drugs in animal models thereby improving drug attrition which is an important challenge in the process of drug development.; Here we present a new chromosome level based version of the Göttingen minipig genome together with a comparative transcriptional analysis of tissues with pharmaceutical relevance as basis for translational research. We relied on mapping and assembly of WGS (whole-genome-shotgun sequencing) derived reads to the reference genome of the Duroc pig and predict 19,228 human orthologous protein-coding genes. Genome-based prediction of the sequence of human drug targets enables the prediction of drug cross-reactivity based on conservation of binding sites. We further support the finding that the genome of Sus scrofa contains about ten-times less pseudogenized genes compared to other vertebrates. Among the functional human orthologs of these minipig pseudogenes we found HEPN1, a putative tumor suppressor gene. The genomes of Sus scrofa, the Tibetan boar, the African Bushpig, and the Warthog show sequence conservation of all inactivating HEPN1 mutations suggesting disruption before the evolutionary split of these pig species. We identify 133 Sus scrofa specific, conserved long non-coding RNAs (lncRNAs) in the minipig genome and show that these transcripts are highly conserved in the African pigs and the Tibetan boar suggesting functional significance. Using a new minipig specific microarray we show high conservation of gene expression signatures in 13 tissues with biomedical relevance between humans and adult minipigs. We underline this relationship for minipig and human liver where we could demonstrate similar expression levels for most phase I drug-metabolizing enzymes. Higher expression levels and metabolic activities were found for FMO1, AKR/CRs and for phase II drug metabolizing enzymes in minipig as compared to human. The variability of gene expression in equivalent human and minipig tissues is considerably higher in minipig organs, which is important for study design in case a human target belongs to this variable category in the minipig. The first analysis of gene expression in multiple tissues during development from young to adult shows that the majority of transcriptional programs are concluded four weeks after birth. This finding is in line with the advanced state of human postnatal organ development at comparative age categories and further supports the minipig as model for pediatric drug safety studies.; Genome based assessment of sequence conservation combined with gene expression data in several tissues improves the translational value of the minipig for human drug development. The genome and gene expression data presented here are important resources for researchers using the minipig as model for biomedical research or commercial breeding. Potential impact of our data for comparative genomics, translational research, and experimental medicine are discussed
Does a colour-coded blood pressure diary improve blood pressure control for patients in general practice: The CoCo trial
BACKGROUND: Insufficient blood pressure control is a frequent problem despite the existence of effective treatment. Insufficient adherence to self-monitoring as well as to therapy is a common reason. Blood pressure self-measurement at home (Home Blood Pressure Measurement, HBPM) has positive effects on treatment adherence and is helpful in achieving the target blood pressure. Only a few studies have investigated whether adherence to HBPM can be improved through simple measures resulting also in better blood pressure control. OBJECTIVE: Improvement of self-monitoring and improved blood pressure control by using a new colour-coded blood pressure diary. OUTCOME: Primary outcome: Change in systolic and/or diastolic blood pressure 6 months after using the new colour-coded blood pressure diary.Secondary outcome: Adherence to blood pressure self-measurement (number of measurements/entries). METHODS/DESIGN: Randomised controlled study.Population: 138 adult patients in primary care with uncontrolled hypertension despite therapy. The control group uses a conventional blood pressure diary; the intervention group uses the new colour-coded blood pressure diary (green, yellow, red according a traffic light system). EXPECTED RESULTS/CONCLUSION: The visual separation and entries in three colour-coded areas reflecting risk (green: blood pressure in the target range 140/>90 mmHg, red: blood pressure in danger zone > 180 mmHg/>110 mmHg) lead to better self-monitoring compared with the conventional (non-colour-coded) blood pressure booklet. The colour-coded, visualised information supports improved perception (awareness and interpretation) of blood pressure and triggers correct behaviour, in the means of improved adherence to the recommended treatment as well as better communication between patients and doctors resulting in improved blood pressure control. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT01013467
Plasma neurofilament light, glial fibrillary acidic protein and lysosphingolipid biomarkers for pharmacodynamics and disease monitoring of GM2 and GM1 gangliosidoses patients
GM2 and GM1 gangliosidoses are genetic, neurodegenerative lysosomal sphingolipid storage disorders. The earlier the age of onset, the more severe the clinical presentation and progression, with infantile, juvenile and late-onset presentations broadly delineated into separate phenotypic subtypes. Gene and substrate reduction therapies, both of which act directly on sphingolipidosis are entering clinical trials for treatment of these disorders. Simple to use biomarkers for disease monitoring are urgently required to support and expedite these clinical trials. Here, lysosphingolipid and protein biomarkers of sphingolipidosis and neuropathology respectively, were assessed in plasma samples from 33 GM2 gangliosidosis patients, 13 GM1 gangliosidosis patients, and compared to 66 controls. LysoGM2 and lysoGM1 were detectable in 31/33 GM2 gangliosidosis and 12/13 GM1 gangliosidosis patient samples respectively, but not in any controls. Levels of the axonal damage marker Neurofilament light (NF-L) were highly elevated in both GM2 and GM1 gangliosidosis patient plasma samples, with no overlap with controls. Levels of the astrocytosis biomarker Glial fibrillary acidic protein (GFAP) were also elevated in samples from both patient populations, albeit with some overlap with controls. In GM2 gangliosidosis patient plasma NF-L, Tau, GFAP and lysoGM2 were all most highly elevated in infantile onset patients, indicating a relationship to severity and phenotype. Plasma NF-L and liver lysoGM2 were also elevated in a GM2 gangliosidosis mouse model, and were lowered by treatment with a drug that slowed disease progression. These results indicate that lysosphingolipids and NF-L/GFAP have potential to monitor pharmacodynamics and pathogenic processes respectively in GM2 and GM1 gangliosidoses patients
Trends in Hospitalizations for Peptic Ulcer Disease, United States, 1998–20051
TOC summary: Decreased hospitalization rates suggest decline in complications from Helicobacter pylori infection
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