Summary
Background
Acute pulmonary embolism (PE) can worsen quality of life due to persistent dyspnea or exercise intolerance.
Objective
Test if tenecteplase increases the probability of a favorable ...composite patient‐oriented outcome after submassive PE.
Methods
Normotensive patients with PE and right ventricular (RV) strain (by echocardiography or biomarkers) were enrolled from eight hospitals. All patients received low‐molecular‐weight heparin followed by random assignment to either a single weight‐based bolus of tenecteplase or placebo, administered in a double‐blinded fashion. The primary composite outcome included: (i) death, circulatory shock, intubation or major bleeding within 5 days or (ii) recurrent PE, poor functional capacity (RV dysfunction with either dyspnea at rest or exercise intolerance) or an SF36® Physical Component Summary (PCS) score < 30 at 90‐day follow‐up.
Results
Eighty‐three patients were randomized; 40 to tenecteplase and 43 to placebo. The trial was terminated prematurely. Within 5 days, adverse outcomes occurred in three placebo‐treated patients (death in one and intubation in two) and one tenecteplase‐treated patient (fatal intracranial hemorrhage). At 90 days, adverse outcomes occurred in 13 unique placebo‐treated patients and five unique tenecteplase‐treated patients Thus, 16 (37%) placebo‐treated and six (15%) tenecteplase‐treated patients had at least one adverse outcome (exact two‐sided P = 0.017).
Conclusions
Treatment of patients with submassive pulmonary embolism with tenecteplase was associated with increased probability of a favorable composite outcome.
Water supply in developing countries is prone to large water losses due to leaky distribution networks and defective sewers, which may affect groundwater quality and quantity in urban areas and ...result in complex subsurface mixing dynamics. In this study, a multi-stable isotope approach was used to investigate spatiotemporal fluctuations of surface and sub-surface water source partitioning and mixing, and to assess nitrogen (N) contamination in the urban water cycle of As-Salt, Jordan. Water import from the King Abdullah Canal (KAC), mains waters from the network, and wastewater are characterized by distinct isotopic signatures, which allowed us to quantify city effluents into the groundwater. Temporal variations in isotopic signatures of polluted groundwater are explained by seasonally fluctuating inflow, and dilution by water that originates from Lake Tiberias and enters the urban water cycle via the KAC. Isotopic analysis (N and O) and comparison between groundwater nitrate and nitrate from mains water, water imports and wastewater confirmed that septic waste from leaky sewers is the main contributor of nitrate contamination. The nitrate of strongly contaminated groundwater was characterized by highest δ15NNO3 values (13.3±1.8‰), whereas lowest δ15NNO3 values were measured in unpolluted groundwater (6.9‰). Analogously, nitrate concentration and isotopic ratios were used for source partitioning and qualitatively confirmed δDH2O and δ18OH2O-based estimates. Dual water isotope endmember mixing calculations suggest that city effluents from leaky networks and sewers contribute 30–64% to the heavily polluted groundwater. Ternary mixing calculations including also chloride revealed that 5–18% of the polluted groundwater is wastewater. Up to two thirds of the groundwater originates from mains, indicating excessive water loss from the network, and calling for improved water supply management.
Display omitted
•A multiple tracer approach was used to study urban water source partitioning and mixing.•First nitrate δ15N and δ18O isotope data of a groundwater in Jordan are presented.•Distinct water δD and δ18O signatures allowed source identification in an urban water cycle.•Endmember mixing calculations revealed significant contributions of city effluents to groundwater.•Leaky networks and sewers contribute between 32% and 71% to polluted groundwater.
In recent decades, muon imaging has found a plethora of applications in many fields. This technique succeeds to infer the density distribution of big inaccessible structures where conventional ...techniques cannot be used. The requirements of different applications demand specific implementations of image reconstruction algorithms for either multiple scattering or absorption-transmission data analysis, as well as noise-suppression filters and muon momentum estimators. This paper presents successful results of image reconstruction techniques applied to simulated data of some representative applications. In addition to well-known reconstruction methods, a novel approach, the so-called μCT, is proposed for the inspection of spent nuclear fuel canisters. Results obtained based on both μCT and the maximum-likelihood expectation maximization reconstruction algorithms are presented.This article is part of the Theo Murphy meeting issue 'Cosmic-ray muography'.
•General population sample (n = 1330) of adults living in a rural region in the northeast of Germany (SHIP).•Shame was the strongest negative predictor for willingness to seek help.•Structured ...estimation modelling showed shame being a full mediator of a negative association between social distance and willingness.
We examined a general population sample (n = 1330) from an epidemiological study (SHIP), investigating whether shame, social distance and reluctance to self-identify as having a mental illness interfere with willingness to seek help for mental health problems. Analyses were stratified for life-time diagnosis of any mental illness. Shame was the strongest negative predictor for willingness to seek help (beta = −0.183, p < .001). Structured Estimation Modelling showed shame being a full mediator of a negative association between social distance and willingness. Our results corroborate the important role of shame as an impediment to help-seeking for mental health problems in the general population.
Prostate stem cell antigen (PSCA) is an attractive antigen to target using therapeutic vaccines because of its overexpression in prostate cancer, especially in metastatic tissues, and its limited ...expression in other organs. Our studies offer the first evidence that a PSCA-based vaccine can induce long-term protection against prostate cancer development in prostate cancer-prone transgenic adenocarcinoma mouse prostate (TRAMP) mice. Eight-week-old TRAMP mice displaying prostate intraepithelial neoplasia were vaccinated with a heterologous prime/boost strategy consisting of gene gun-delivered PSCA-cDNA followed by Venezuelan equine encephalitis virus replicons encoding PSCA. Our results show the induction of an immune response against a newly defined PSCA epitope that is mediated primarily by CD8 T cells. The prostates of PSCA-vaccinated mice were infiltrated by CD4-positive, CD8-positive, CD11b-positive, and CD11c-positive cells. Vaccination induced MHC class I expression and cytokine production IFN-gamma, tumor necrosis factor-alpha, interleukin 2 (IL-2), IL-4, and IL-5 within prostate tumors. This tumor microenvironment correlated with low Gleason scores and weak PSCA staining on tumor cells present in hyperplastic zones and in areas that contained focal and well-differentiated adenocarcinomas. PSCA-vaccinated TRAMP mice had a 90% survival rate at 12 months of age. In contrast, all control mice had succumbed to prostate cancer or had heavy tumor loads. Crucially, this long-term protective immune response was not associated with any measurable induction of autoimmunity. The possibility of inducing long-term protection against prostate cancer by vaccination at the earliest signs of its development has the potential to cause a dramatic paradigm shift in the treatment of this disease.
PDF
