Purpose
Prior studies identified high variability in prevalence of withdrawal of life-sustaining treatment in the ICU. Variability in end-of-life decision-making has been reported at many levels: ...between countries, ICUs, and individual intensivists. We performed a systematic review examining regional, national, inter-hospital, and inter-physician variability in withdrawal of life-sustaining treatment in the ICU.
Methods
Using a predefined search strategy, we queried three electronic databases for peer-reviewed articles addressing withdrawal of life-sustaining treatment in adult patients in the ICU. Data were analyzed for variability in prevalence of withdrawal of life-sustaining treatment. Withholding of life-sustaining treatment was also examined where information was provided. An assessment tool was developed to quantify the risk of bias in the included articles.
Results
We identified 1284 studies, with 56 included after review. Most studies had unclear or high risk of bias, primarily due to unclear case definitions or potential confounding. The mean prevalence of withdrawal of life-sustaining treatment for patients who died varied from 0 to 84.1 % between studies, with standard deviation of 23.7 %. Sensitivity analysis of general ICU patients yielded similar results. Withholding also varied between 5.3 and 67.3 % (mean 27.3, SD 18.5 %). Substantial variability was found between world regions, countries, individual ICUs within a country, and individual intensivists within one ICU.
Conclusions
We identified substantial variability in the withdrawal of life-sustaining treatment across world regions and countries. Similar variability existed between ICUs within countries and even between providers within the same ICU. Further study is necessary, and could lead to interventions to improve end-of-life care in the ICU.
Primary liver cancer is the third leading cause of cancer related deaths worldwide, and the disease is associated with high incidence rate of thrombosis. Studies indicate that Tissue Factor Pathway ...Inhibitor (TFPI) plays a role in cancer development. We aimed to study its expression, clinical role and regulation by micro RNAs (miRNAs) in hepatocellular carcinoma (HCC).
Publically available datasets were used for clinical analysis of TFPI and miRNAs expression by web analysis tools. miRNA mimics targeting TFPIα 3’untranslated region (UTR) were selected from target prediction programs and verified by luciferase reporter assay. In vitro effects of miRNAs overexpression in HCC cell lines on TFPI expression and cell proliferation and apoptosis were analysed.
TFPI expression was significantly increased in HCC tumours compared to normal tissue.
Low TFPI tumour expression was associated with better survival probability. Four candidate miRNAs were selected from the target prediction programs. miR-7-5p and miR-1236-3p were validated in HepG2 and Huh7 cells to reduce TFPI mRNA and protein levels following overexpression. Furthermore, miR-7-5p and miR-1236-3p reduced TFPIα-3’UTR-controlled luciferase activity. The two validated miRNAs inhibited proliferation of HepG2 cells, and had clinical significance in HCC.
TFPI was increased in HCC tumours compared to normal tissue and high TFPI expression was associated with an unfavorable outcome in HCC patients. miR-7-5p and miR-1236-3p were identified as novel regulators of TFPI in vitro.
•HCC is among the cancer types with highest expression of TFPI, and the expression is increased compared to normal tissue.•High TFPI expression was associated with an unfavorable outcome in HCC patients•miR-7-5p and miR-1236-3p were identified as novel regulators of TFPI in liver cancer cells•This study provides further evidence of miRNAs as regulators of hemostatic proteins in HCC
The vascular endothelium is critical for maintenance of cardiovascular homeostasis. Endothelial dysfunction is a key event of atherosclerosis, with oxidative stress mediated by reactive oxygen ...species (ROS) playing a major role. Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is increasingly recognised to play a protective role in atherosclerosis, however the molecular mechanisms by which it exerts its beneficial effects are unclear. Here we examined if TRAIL could attenuate vascular oxidative stress and improve endothelial cell (EC) function. In coronary artery disease patients, plasma TRAIL levels were significantly reduced compared to healthy individuals, and negatively correlated with the levels of circulating 8-iso Prostaglandin F2α, a marker of in vivo oxidative stress. In vivo, high-fat fed, atherosclerotic Trail-/-Apoe-/- mice exhibited a significant impairment in endothelial-dependent vasorelaxation, which correlated with increased vascular ROS and 4-hydroxynonenal compared to Apoe-/- mice. Endothelial permeability measured by Evan's blue dye extravasation was increased in several organs of Trail-/- mice compared to wild-type mice, which correlated with a decrease in VE-cadherin expression. In vitro in ECs, angiotensin II (AngII)-induced ROS generation involving the mitochondria, NADPH oxidase-4 (NOX-4) and eNOS, was inhibited by pre-treatment with TRAIL. Furthermore, AngII-augmented VCAM-1 expression and monocyte adhesion to ECs was inhibited by TRAIL. Finally, AngII reduced VE-cadherin expression and redistributed this protein, all of which was brought back to baseline by TRAIL pre-treatment. These findings demonstrate for the first time that TRAIL protects against several forms of endothelial dysfunction involving its ability to control EC ROS generation. Understanding the role TRAIL plays in normal physiology and disease, may lead to potential new therapies to improve endothelial function and atherosclerosis.
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•Plasma TRAIL negatively associates with circulating 8-iso prostaglandin F2α levels in CAD patients.•TRAILdeletion in mice promotes oxidative stress, impaired endothelial-dependent relaxation and elevates permeability.•TRAIL protects against AngII-induced oxidative stress in ECs by limiting ROS generation.•TRAIL limits AngII-induced VCAM-1 expression and monocyte adhesion to ECs.•TRAIL limits AngII-mediated disruption of VE-cadherin plasma membrane localisation, and downregulation of its expression.
We present far-infrared observations of Monoceros R2 (a giant molecular cloud at approximately 830 pc distance, containing several sites of active star formation), as observed at 70 μm, 160 μm, 250 ...μm, 350 μm, and 500 μm by the Photodetector Array Camera and Spectrometer (PACS) and Spectral and Photometric Imaging Receiver (SPIRE) instruments on the Herschel Space Observatory as part of the Herschel imaging survey of OB young stellar objects (HOBYS) Key programme. The Herschel data are complemented by SCUBA-2 data in the submillimetre range, and WISE and Spitzer data in the mid-infrared. In addition, C18O data from the IRAM 30-m Telescope are presented, and used for kinematic information. Sources were extracted from the maps with getsources, and from the fluxes measured, spectral energy distributions were constructed, allowing measurements of source mass and dust temperature. Of177 Herschel sources robustly detected in the region (a detection with high signal-to-noise and low axis ratio at multiple wavelengths), including protostars and starless cores, 29 are found in a filamentary hub at the centre of the region (a little over 1% of the observed area). These objects are on average smaller, more massive, and more luminous than those in the surrounding regions (which together suggest that they are at a later stage of evolution), a result that cannot be explained entirely by selection effects. These results suggest a picture in which the hub may have begun star formation at a point significantly earlier than the outer regions, possibly forming as a result of feedback from earlier star formation. Furthermore, the hub may be sustaining its star formation by accreting material from the surrounding filaments.
Low-density lipoprotein (LDL) modified by hypochlorous acid (HOCl) produced by myeloperoxidase (MPO) is present in atherosclerotic lesions, where it is implicated in the propagation of inflammation ...and acceleration of lesion development by multiple pathways, including the induction of endothelial dysfunction. Thiocyanate (SCN-) ions are utilised by MPO to produce the oxidant hypothiocyanous acid (HOSCN), which reacts with LDL in a different manner to HOCl. Whilst the reactivity of HOCl-modified LDL has been previously studied, the role of HOSCN in the modification of LDL in vivo is poorly defined, although emerging evidence suggests that these particles have distinct biological properties. This is important because elevated plasma SCN- is linked with both the propagation and prevention of atherosclerosis. In this study, we demonstrate that both HOSCN- and HOCl-modified LDL inhibit endothelium-mediated vasorelaxation ex vivo in rat aortic ring segments. In vitro experiments with human coronary artery endothelial cells show that HOSCN-modified LDL decreases in the production of nitric oxide (NO•) and induces the loss of endothelial nitric oxide synthase (eNOS) activity. This occurs to a similar extent to that seen with HOCl-modified LDL. In each case, these effects are related to eNOS uncoupling, rather than altered expression, phosphorylation or cellular localisation. Together, these data provide new insights into role of MPO and LDL modification in the induction of endothelial dysfunction, which has implications for both the therapeutic use of SCN- within the setting of atherosclerosis and for smokers, who have elevated plasma levels of SCN-, and are more at risk of developing cardiovascular disease.
•Myeloperoxidase produces HOCl and HOSCN that modify LDL in a distinct manner.•HOSCN- and HOCl-LDL inhibit endothelium-mediated vasorelaxation in aortic rings ex vivo.•HOSCN- and HOCl-LDL decrease endothelial production of nitric oxide in vitro.•Decreased eNOS activity is seen, which associated with enzyme uncoupling.•HOSCN- and HOCl-LDL induce colocalisation of eNOS and caveolin 1.
•Global ecosystem assessments inform conservation funding priorities.•Seagrass, saltmarsh and mangroves are under-recognized in global assessments.•Ecosystem assessments often overlook important ...functions, like fishery nurseries.•Synthesis could fill gaps in data for global scale assessments.•We recommend priorities for filling gaps in global assessments.
Vegetated coastal wetlands, including seagrass, saltmarsh and mangroves, are threatened globally, yet the need to avert these losses is poorly recognized in international policy, such as in the Convention on Biological Diversity and the United Nations (UN) Sustainable Development Goals. Identifying the impact of overlooking coastal wetlands in ecosystem assessment frameworks could help prioritize research efforts to fill these gaps. Here, we examine gaps in the recognition of coastal wetlands in globally applicable ecosystem assessments. We address both shortfalls in assessment frameworks when it comes to assessing wetlands, and gaps in data that limit widespread application of assessments. We examine five assessment frameworks that track fisheries, greenhouse gas emissions, ecosystem threats, and ecosystem services. We found that these assessments inform management decisions, but that the functions provided by coastal wetlands are incompletely represented. Most frameworks had sufficient complexity to measure wetland status, but limitations in data meant they were incompletely informed about wetland functions and services. Incomplete representation of coastal wetlands may lead to them being overlooked by research and management. Improving the coverage of coastal wetlands in ecosystem assessments requires improving global scale mapping of wetland trends, developing global-scale indicators of wetland function and synthesis to quantitatively link animal population dynamics to wetland trends. Filling these gaps will help ensure coastal wetland conservation is properly informed to manage them for the outstanding benefits they bring humanity.
•Exploratory analysis allowed to extract remarkable insights from data.•Building energy simulations provided data to assess climatic zone methods.•Uniqueness and dispersion were used as performance ...indicators for the assessment.•Building performance data has the potential to improve climatic zonings.
Climatic zoning is frequently used in building energy efficiency regulations. However, there is no consensus about which climatic zoning method should be used for a given purpose. This study aims to verify if building performance data is necessary to propose a climatic zoning for building energy efficiency regulations. First, an exploratory data analysis was performed based on correlations of climatic variables and building performance results from an office building in 411 Brazilian cities. The same building performance results were used to perform a preliminary assessment of seven climatic zoning methods: two globally well-known methods (ASHRAE 169 and Koppen-Geiger), the current Brazilian regulation method (NBR 15220), a proposal for a new Brazilian regulation (Roriz) and three alternative methods for climatic zoning proposed by the authors. The alternative methods were named as Data-driven, Enhanced degree-day and Decision tree method. The final assessment included 21 variations in the office building. The performance of each climatic zoning method was analysed according to two indicators: uniqueness and dispersion. This study shows the importance of building performance data to improve the quality of climatic zonings for building energy efficiency regulations.
•Coordinated conservation requires clear indicator interrelationships.•We analyse and interrogate global ecosystem indicators for coastal wetlands.•We develop spatially explicit typologies of ...ecosystem status at the global scale.•Typologies identify diverse conservation and management needs of coastal wetlands.•Simplifying the complex global mosaic of status informs management and conservation.
Global-scale conservation initiatives and policy instruments rely on ecosystem indicators to track progress towards targets and objectives. A deeper understanding of indicator interrelationships would benefit these efforts and help characterize ecosystem status. We study interrelationships among 34 indicators for mangroves, saltmarsh, and seagrass ecosystems, and develop data-driven, spatially explicit typologies of coastal wetland status at a global scale. After accounting for environmental covariates and gap-filling missing data, we obtained two levels of clustering at 5 and 18 typologies, providing outputs at different scales for different end users. We generated 2,845 cells (1° (lat) × 1° (long)) globally, of which 29.7% were characterized by high land- and marine-based impacts and a high proportion of threatened species, 13.5% by high climate-based impacts, and 9.6% were refuges with lower impacts, high fish density and a low proportion of threatened species. We identify instances where specific actions could have positive outcomes for coastal wetlands across regions facing similar issues. For example, land- and marine-based threats to coastal wetlands were associated with ecological structure and function indicators, suggesting that reducing these threats may reduce habitat degradation and threats to species persistence. However, several interdimensional relationships might be affected by temporal or spatial mismatches in data. Weak relationships mean that global biodiversity maps that categorize areas by single indicators (such as threats or trends in habitat size) may not be representative of changes in other indicators (e.g., ecosystem function). By simplifying the complex global mosaic of coastal wetland status and identifying regions with similar issues that could benefit from knowledge exchange across national boundaries, we help set the scene for globally and regionally coordinated conservation.
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