Literature data are collated for 38 stripped-envelope core-collapse supernovae (SE SNe; i.e. SNe IIb, Ib, Ic and Ic-BL) that have good light-curve coverage in more than one optical band. Using ...bolometric corrections derived in previous work, the bolometric light curve of each SN is recovered and template bolometric light curves provided. Peak light distributions and decay rates are investigated; SNe subtypes are not cleanly distinguished in this parameter space, although some grouping of types does occur and there is a suggestion of a Phillips-like relation for most SNe Ic-BL. The bolometric light curves are modelled with a simple analytical prescription and compared to results from more detailed modelling. Distributions of the explosion parameters show the extreme nature of SNe Ic-BL in terms of their 56Ni mass and the kinetic energy, however ejected masses are similar to other subtypes. SNe Ib and Ic have very similar distributions of explosion parameters, indicating a similarity in progenitors. SNe IIb are the most homogeneous subtype and have the lowest average values for 56Ni mass, ejected mass, and kinetic energy. Ejecta masses for each subtype and SE SNe as a whole are inconsistent with those expected from very massive stars. The majority of the ejecta mass distribution is well described by more moderately massive progenitors in binaries, indicating these are the dominant progenitor channel for SE SNe.
Imaging Atherosclerosis Tarkin, Jason M; Dweck, Marc R; Evans, Nicholas R ...
Circulation research,
2016-February-19, 2016-Feb-19, 2016-02-19, 20160219, Volume:
118, Issue:
4
Journal Article
Peer reviewed
Open access
Advances in atherosclerosis imaging technology and research have provided a range of diagnostic tools to characterize high-risk plaque in vivo; however, these important vascular imaging methods ...additionally promise great scientific and translational applications beyond this quest. When combined with conventional anatomic- and hemodynamic-based assessments of disease severity, cross-sectional multimodal imaging incorporating molecular probes and other novel noninvasive techniques can add detailed interrogation of plaque composition, activity, and overall disease burden. In the catheterization laboratory, intravascular imaging provides unparalleled access to the world beneath the plaque surface, allowing tissue characterization and measurement of cap thickness with micrometer spatial resolution. Atherosclerosis imaging captures key data that reveal snapshots into underlying biology, which can test our understanding of fundamental research questions and shape our approach toward patient management. Imaging can also be used to quantify response to therapeutic interventions and ultimately help predict cardiovascular risk. Although there are undeniable barriers to clinical translation, many of these hold-ups might soon be surpassed by rapidly evolving innovations to improve image acquisition, coregistration, motion correction, and reduce radiation exposure. This article provides a comprehensive review of current and experimental atherosclerosis imaging methods and their uses in research and potential for translation to the clinic.
Patients with chronic kidney disease (CKD) have an enhanced risk of cardiovascular (CV) morbidity and mortality when compared with age- and gender-matched individuals with normal kidney function. ...Trimethlyamine N-oxide (TMAO) is a gut-derived amine oxide that has been implicated in the causation of CV diseases. Plasma TMAO is cleared by the kidney, and TMAO levels are elevated in CKD. Experimental studies have identified pathogenic mechanisms by which TMAO may contribute to CV disease through dysregulation of lipid metabolism, enhanced macrophage foam cell formation, and platelet dysfunction. Safe and well-tolerated therapeutic interventions such as pre- and probiotics, which modify the gut microbiome, offer the opportunity for interventional studies. This review examines the pathogenicity of TMAO, its value as a biomarker, and its potential as a therapeutic target in the context of CKD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Kynurenine monooxygenase (KMO) blockade protects against multiple organ failure caused by acute pancreatitis (AP), but the link between KMO and systemic inflammation has eluded discovery until now. ...Here, we show that the KMO product 3-hydroxykynurenine primes innate immune signaling to exacerbate systemic inflammation during experimental AP. We find a tissue-specific role for KMO, where mice lacking Kmo solely in hepatocytes have elevated plasma 3-hydroxykynurenine levels that prime inflammatory gene transcription. 3-Hydroxykynurenine synergizes with interleukin-1β to cause cellular apoptosis. Critically, mice with elevated 3-hydroxykynurenine succumb fatally earlier and more readily to experimental AP. Therapeutically, blockade with the highly selective KMO inhibitor GSK898 rescues the phenotype, reducing 3-hydroxykynurenine and protecting against critical illness and death. Together, our findings establish KMO and 3-hydroxykynurenine as regulators of inflammation and the innate immune response to sterile inflammation. During critical illness, excess morbidity and death from multiple organ failure can be rescued by systemic KMO blockade.
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•KMO activity primes innate immune and inflammatory gene transcription through 3HK production•3HK synergizes with interleukin-1β to cause cell apoptosis•Therapeutic KMO blockade rescues fatal inflammation in experimental acute pancreatitis
Hayes et al. characterize a metabolic link between 3-hydroxykynurenine generated by KMO activity and priming of innate immune gene transcription during systemic inflammation. Therapeutic blockade using the highly specific KMO inhibitor GSK898 rescues the phenotype and protects against excess morbidity and death from multiple organ failure in experimental acute pancreatitis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Through the creation of spectral energy distributions for well-observed literature core-collapse supernovae (CCSNe), we present corrections to transform optical light curves to full bolometric light ...curves. These corrections take the form of parabolic fits to optical colours, with B − I and g − r presented as exemplary fits, while parameters for fits to other colours are also given. We find evolution of the corrections with colour to be extremely homogeneous across CCSNe of all types in the majority of cases, and also present fits for stripped-envelope and Type II SNe separately. A separate fit, appropriate for SNe exhibiting strong emission due to cooling after shock breakout, is presented. Such a method will homogenize the creation of bolometric light curves for CCSNe where observations cannot constrain the emitted flux - of particular importance for current and future SN surveys where typical follow-up of the vast majority of events will occur only in the optical window, resulting in consistent comparisons of modelling involving bolometric light curves. Test cases for SNe 1987A and 2009jf using the method presented here are shown, and the bolometric light curves are recovered with excellent accuracy in each case.
The warmest global temperatures of the past 85 million years occurred during a prolonged greenhouse episode known as the Early Eocene Climatic Optimum (52–50 Ma). The Early Eocene Climatic Optimum ...terminated with a long-term cooling trend that culminated in continental-scale glaciation of Antarctica from 34 Ma onward. Whereas early studies attributed the Eocene transition from greenhouse to icehouse climates to the tectonic opening of Southern Ocean gateways, more recent investigations invoked a dominant role of declining atmospheric greenhouse gas concentrations (e.g., CO ₂). However, the scarcity of field data has prevented empirical evaluation of these hypotheses. We present marine microfossil and organic geochemical records spanning the early-to-middle Eocene transition from the Wilkes Land Margin, East Antarctica. Dinoflagellate biogeography and sea surface temperature paleothermometry reveal that the earliest throughflow of a westbound Antarctic Counter Current began ∼49–50 Ma through a southern opening of the Tasmanian Gateway. This early opening occurs in conjunction with the simultaneous onset of regional surface water and continental cooling (2–4 °C), evidenced by biomarker- and pollen-based paleothermometry. We interpret that the westbound flowing current flow across the Tasmanian Gateway resulted in cooling of Antarctic surface waters and coasts, which was conveyed to global intermediate waters through invigorated deep convection in southern high latitudes. Although atmospheric CO ₂ forcing alone would provide a more uniform middle Eocene cooling, the opening of the Tasmanian Gateway better explains Southern Ocean surface water and global deep ocean cooling in the apparent absence of (sub-) equatorial cooling.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Summary Background Emotional stress is associated with increased risk of cardiovascular disease. We imaged the amygdala, a brain region involved in stress, to determine whether its resting metabolic ...activity predicts risk of subsequent cardiovascular events. Methods Individuals aged 30 years or older without known cardiovascular disease or active cancer disorders, who underwent18 F-fluorodexoyglucose PET/CT at Massachusetts General Hospital (Boston, MA, USA) between Jan 1, 2005, and Dec 31, 2008, were studied longitudinally. Amygdalar activity, bone-marrow activity, and arterial inflammation were assessed with validated methods. In a separate cross-sectional study we analysed the relation between perceived stress, amygdalar activity, arterial inflammation, and C-reactive protein. Image analyses and cardiovascular disease event adjudication were done by mutually blinded researchers. Relations between amygdalar activity and cardiovascular disease events were assessed with Cox models, log-rank tests, and mediation (path) analyses. Findings 293 patients (median age 55 years IQR 45·0–65·5) were included in the longitudinal study, 22 of whom had a cardiovascular disease event during median follow-up of 3·7 years (IQR 2·7–4·8). Amygdalar activity was associated with increased bone-marrow activity ( r =0·47; p<0·0001), arterial inflammation ( r =0·49; p<0·0001), and risk of cardiovascular disease events (standardised hazard ratio 1·59, 95% CI 1·27–1·98; p<0·0001), a finding that remained significant after multivariate adjustments. The association between amygdalar activity and cardiovascular disease events seemed to be mediated by increased bone-marrow activity and arterial inflammation in series. In the separate cross-sectional study of patients who underwent psychometric analysis (n=13), amygdalar activity was significantly associated with arterial inflammation ( r =0·70; p=0·0083). Perceived stress was associated with amygdalar activity ( r =0·56; p=0·0485), arterial inflammation ( r =0·59; p=0·0345), and C-reactive protein ( r =0·83; p=0·0210). Interpretation In this first study to link regional brain activity to subsequent cardiovascular disease, amygdalar activity independently and robustly predicted cardiovascular disease events. Amygdalar activity is involved partly via a path that includes increased bone-marrow activity and arterial inflammation. These findings provide novel insights into the mechanism through which emotional stressors can lead to cardiovascular disease in human beings. Funding None.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
•A Monte-Carlo simulation of the progression of a snooker frame is developed.•The development of dynamic measures of player performance is advocated.•Analysis of how a frame's progression and outcome ...depend on player ability.•Assessment of the influence of the break-off shot on the progression of a frame.•Indictive strategies are conceived when snookered or faced with a risky pot.
This paper is the first to develop a Monte Carlo simulation model of a snooker frame, using post-match video analysis of over 30,000 shots to inform the probability that a top professional will pot a ball on each shot depending on the number of balls remaining on the table and the status of their current visit to the table. We demonstrate that this accurately reflects the progression of a frame at this level, advocating new approaches in viewing a frame as a succession of scoring visits and in using dynamic measures to evaluate player performance. The simulation model also produces a realistic expectation of the probability that the frame will be won from any given position. The model is then used to analyse the effectiveness of the break-off shot and the influence that this has on the outcome of the frame. We also use simulated outcomes to evaluate the choice between taking on a risky pot or playing safe and the merits of alternative approaches to escaping from a snooker.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Introduction
Ipilimumab, a cytotoxic T lymphocyte-associated antigen-4 blocking antibody, has improved overall survival (OS) in metastatic melanoma in phase III trials. However, about 80 % of ...patients fail to respond, and no predictive markers for benefit from therapy have been identified. We analysed a ‘real world’ population of patients treated with ipilimumab to identify markers for treatment benefit.
Methods
Patients with advanced cutaneous melanoma were treated in the Netherlands (NL) and the United Kingdom (UK) with ipilimumab at 3 mg/kg. Baseline characteristics and peripheral blood parameters were assessed, and patients were monitored for the occurrence of adverse events and outcomes.
Results
A total of 166 patients were treated in the Netherlands. Best overall response and disease control rates were 17 and 35 %, respectively. Median follow-up was 17.9 months, with a median progression-free survival of 2.9 months. Median OS was 7.5 months, and OS at 1 year was 37.8 % and at 2 years was 22.9 %. In a multivariate model, baseline serum lactate dehydrogenase (LDH) was demonstrated to be the strongest predictive factor for OS. These findings were validated in an independent cohort of 64 patients from the UK.
Conclusion
In both the NL and UK cohorts, long-term benefit of ipilimumab treatment was unlikely for patients with baseline serum LDH greater than twice the upper limit of normal. In the absence of prospective data, clinicians treating melanoma may wish to consider the data presented here to guide patient selection for ipilimumab therapy.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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