Bicuspid aortic valve disease is the most common congenital cardiac disorder, being present in 1% to 2% of the general population. Associated aortopathy is a common finding in patients with bicuspid ...aortic valve disease, with thoracic aortic dilation noted in approximately 40% of patients in referral centers. Several previous consensus statements and guidelines have addressed the management of bicuspid aortic valve–associated aortopathy, but none focused entirely on this disease process. The current guidelines cover all major aspects of bicuspid aortic valve aortopathy, including natural history, phenotypic expression, histology and molecular pathomechanisms, imaging, indications for surgery, surveillance, and follow-up, and recommendations for future research. It is intended to provide clinicians with a current and comprehensive review of bicuspid aortic valve aortopathy and to guide the daily management of these complex patients.
We identified 100 scientific questions that, if answered, would have the greatest impact on conservation practice and policy. Representatives from 21 international organizations, regional sections ...and working groups of the Society for Conservation Biology, and 12 academics, from all continents except Antarctica, compiled 2291 questions of relevance to conservation of biological diversity worldwide. The questions were gathered from 761 individuals through workshops, email requests, and discussions. Voting by email to short-list questions, followed by a 2-day workshop, was used to derive the final list of 100 questions. Most of the final questions were derived through a process of modification and combination as the workshop progressed. The questions are divided into 12 sections: ecosystem functions and services, climate change, technological change, protected areas, ecosystem management and restoration, terrestrial ecosystems, marine ecosystems, freshwater ecosystems, species management, organizational systems and processes, societal context and change, and impacts of conservation interventions. We anticipate that these questions will help identify new directions for researchers and assist funders in directing funds.
Objective
Previous research has demonstrated a robust relationship between religion and well‐being, and it has been proposed that positive emotions are important mediators of this effect. Yet the ...mechanism via which religion promotes positive emotions has not been widely studied. We sought to examine whether teleological explanations of daily events and resulting positive emotions serially mediated the effects of religion on well‐being.
Method
These hypotheses were tested over three studies involving full‐time and part‐time university students in Singapore. In Study 1, participants completed measures of religiousness and well‐being, and explained and described three recent personally significant events and their resulting emotions. Studies 2 and 3 adopted an ecological momentary assessment approach to measure teleological explanations, resulting emotions, and well‐being in almost real time.
Results
In Study 1, teleological explanations and positive emotions serially mediated the effects of religiousness on well‐being. In Study 2, momentary teleological explanations of daily events mediated the positive relationship between religiousness and momentary positive emotions. In Study 3, serial mediation of the relationship between religiousness and momentary well‐being by momentary teleological explanations and positive emotions was observed.
Conclusions
These results provide evidence of the importance of teleological explanations of daily events in religious enhancement of well‐being.
The hemocompatibility of plasma-treated, silicon-incorporated, diamond-like carbon (Si-DLC) films was investigated. Si-DLC films with a Si concentration of 2at.% were prepared on Si (100) or Nitinol ...substrates using a capacitively coupled radiofrequency plasma-assisted chemical vapor deposition method using a mixed gas of benzene (C(6)H(6)) and diluted silane (SiH(4):H(2)=10:90). The Si-DLC films were then treated with O(2), CF(4) or N(2) glow discharge for surface modification. The plasma treatment revealed an intimate relationship between the polar component of the surface energy and its hemocompatibility. All in vitro characterizations, i.e. protein absorption behavior, activated partial thromboplastin time measurement and platelet adhesion behavior, showed improved hemocompatibility of the N(2-)- or O(2)-plasma-treated surfaces where the polar component of the surface energy was significantly increased. Si-O or Si-N surface bonds played an important role in improving hemocompatibility, as observed in a model experiment. These results support the importance of a negatively charged polar component of the surface in inhibiting fibrinogen adsorption and platelet adhesion.
Purpose The role of adjuvant chemotherapy (AC) or induction chemotherapy (IC) in the treatment of locally advanced nasopharyngeal carcinoma is controversial. The individual patient data from the ...Meta-Analysis of Chemotherapy in Nasopharynx Carcinoma database were used to compare all available treatments. Methods All randomized trials of radiotherapy (RT) with or without chemotherapy in nonmetastatic nasopharyngeal carcinoma were considered. Overall, 20 trials and 5,144 patients were included. Treatments were grouped into seven categories: RT alone (RT), IC followed by RT (IC-RT), RT followed by AC (RT-AC), IC followed by RT followed by AC (IC-RT-AC), concomitant chemoradiotherapy (CRT), IC followed by CRT (IC-CRT), and CRT followed by AC (CRT-AC). P-score was used to rank the treatments. Fixed- and random-effects frequentist network meta-analysis models were applied. Results The three treatments with the highest probability of benefit on overall survival (OS) were CRT-AC, followed by CRT and IC-CRT, with respective hazard ratios (HRs 95% CIs) compared with RT alone of 0.65 (0.56 to 0.75), 0.77 (0.64 to 0.92), and 0.81 (0.63 to 1.04). HRs (95% CIs) of CRT-AC compared with CRT for OS, progression-free survival (PFS), locoregional control, and distant control (DC) were, respectively, 0.85 (0.68 to 1.05), 0.81 (0.66 to 0.98), 0.70 (0.48 to 1.02), and 0.87 (0.61 to 1.25). IC-CRT ranked second for PFS and the best for DC. CRT never ranked first. HRs of CRT compared with IC-CRT for OS, PFS, locoregional control, and DC were, respectively, 0.95 (0.72 to 1.25), 1.13 (0.88 to 1.46), 1.05 (0.70 to 1.59), and 1.55 (0.94 to 2.56). Regimens with more chemotherapy were associated with increased risk of acute toxicity. Conclusion The addition of AC to CRT achieved the highest survival benefit and consistent improvement for all end points. The addition of IC to CRT achieved the highest effect on DC.
Summary Background The multitargeted kinase inhibitors sorafenib and sunitinib have improved treatment of solid tumours including renal cell carcinoma and hepatocellular carcinoma by offering better ...clinical responses. However, sorafenib and sunitinib are commonly associated with cutaneous toxicity.
Objectives We conducted this study to make a clinical assessment of the cutaneous toxicities induced by the oral multitargeted kinase inhibitors sorafenib and sunitinib.
Methods Retrospectively, we reviewed medical records of patients receiving multitargeted kinase inhibitors, including 109 patients on sorafenib for the treatment of renal cell carcinoma or hepatocellular carcinoma and 119 patients receiving sunitinib for treatment of renal cell carcinoma or a gastrointestinal stromal tumour. Clinical data on cutaneous toxicities were collated. We describe the incidences and intensities of toxicities, and analyse the data statistically.
Results The most common cutaneous toxicity was hand‐and‐foot skin reaction (HFSR). Other cutaneous toxicities included alopecia, stomatitis, skin discoloration (hair or face), subungual splinter haemorrhage, facial swelling, facial erythema and xerosis. HFSR and severe stomatitis required therapy modifications to relieve symptoms, but other cutaneous toxicities did not affect treatment course. HFSR was observed in 48% of patients treated with sorafenib and 36% of those treated with sunitinib. Median time to onset was 18·4 days in patients receiving sorafenib and 32·4 days in those receiving sunitinib. HFSR and stomatitis were early symptoms compared with other cutaneous toxicities. Patients with severe HFSR were likely to develop the symptoms at early phases of therapy. A significant correlation between the severity of HFSR and development of alopecia and stomatitis was found.
Conclusions Multitargeted kinase inhibitors are associated with a significant risk of various cutaneous adverse events. HFSR is the commonest and most serious cutaneous toxicity in patients treated with these drugs.
Long-duration gamma-ray bursts (GRBs) are widely believed to be highly collimated explosions (bipolar conical outflows with half-opening angle theta{approx} 1{sup 0}-10{sup 0}). As a result of this ...beaming factor, the true energy release from a GRB is usually several orders of magnitude smaller than the observed isotropic value. Measuring this opening angle, typically inferred from an achromatic steepening in the afterglow light curve (a 'jet' break), has proven exceedingly difficult in the Swift era. Here, we undertake a study of five of the brightest (in terms of the isotropic prompt gamma-ray energy release, E{sub g}amma{sub ,iso}) GRBs in the Swift era to search for jet breaks and hence constrain the collimation-corrected energy release. We present multi-wavelength (radio through X-ray) observations of GRBs 050820A, 060418, and 080319B, and construct afterglow models to extract the opening angle and beaming-corrected energy release for all three events. Together with results from previous analyses of GRBs 050904 and 070125, we find evidence for an achromatic jet break in all five events, strongly supporting the canonical picture of GRBs as collimated explosions. The most natural explanation for the lack of observed jet breaks from most Swift GRBs is therefore selection effects. However, the opening angles for the events in our sample are larger than would be expected if all GRBs had a canonical energy release of {approx}10{sup 51} erg. The total energy release we measure for the 'hyper-energetic' (E{sub tot} {approx}> 10{sup 52} erg) events in our sample is large enough to start challenging models with a magnetar as the compact central remnant.
Cardiac amyloidosis is emerging as an underdiagnosed cause of heart failure and mortality. Growing literature suggests that a noninvasive diagnosis of cardiac amyloidosis is now feasible. However, ...the diagnostic criteria and utilization of imaging in cardiac amyloidosis are not standardized. In this paper, Part 2 of a series, a panel of international experts from multiple societies define the diagnostic criteria for cardiac amyloidosis and appropriate utilization of echocardiography, cardiovascular magnetic resonance imaging, and radionuclide imaging in the evaluation of patients with known or suspected cardiac amyloidosis.
Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant disease, where even surgical resection and aggressive chemotherapy produce dismal outcomes. Immunotherapy is a promising alternative to ...conventional treatments, possessing the ability to elicit T cell-mediated killing of tumor cells and prevent disease recurrence. Immunotherapeutic approaches thus far have seen limited success in PDAC due to a poorly immunogenic and exceedingly immunosuppressive tumor microenvironment, which is enriched with dysfunctional and immunosuppressed antigen-presenting cells (APCs). We developed a highly potent immunostimulatory nanoparticle (immuno-NP) to activate and expand APCs in the tumor and induce local secretion of interferon β (IFNβ), which is a pro-inflammatory cytokine that plays a major role in APC recruitment. The effectiveness of the immuno-NP stems from its dual cargo of two synergistic immune modulators consisting of an agonist of the stimulator of interferon genes (STING) pathway and an agonist of the Toll-like receptor 4 (TLR4) pathway. We show the functional synergy of the dual-agonist cargo can be tweaked by adjusting the ratio of the two agonists loaded in the immuno-NP, leading to an increase in IFNβ production (11-fold) compared to any single agonist immuno-NP variant. Using the orthotopic murine Panc02 model of PDAC, we show that systemic administration allowed immuno-NPs to deposit into the perivascular regions of the tumor, which coincided with the APC-rich tumor areas leading to predominant uptake of immuno-NPs by APCs. The immuno-NPs were effectively taken up by a significant portion of dendritic cells in the tumor (>56%). This led to a significant expansion of APCs, resulting in an 11.5-fold increase of dendritic cells and infiltration of lymphocytes throughout the pancreatic tumor compared to untreated animals.
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•Nanoparticle is loaded with two potent innate immune agonists.•The dual-agonist cargo provides remarkable functional synergy.•Systemic delivery enables uptake by APCs in perivascular regions of tumors.•Significant activation and expansion of APCs in pancreatic tumor.
Bicuspid aortic valve disease is a common congenital cardiac disorder, being present in 1% to 2% of the general population. Associated aortopathy is a common finding in patients with bicuspid aortic ...valve disease, with thoracic aortic dilation noted in approximately 40% of patients in referral centers. Several previous consensus statements and guidelines have addressed the management of bicuspid aortic valve–associated aortopathy, but none focused entirely on this disease process. The current document is an executive summary of “The American Association for Thoracic Surgery Guidelines on Bicuspid Aortic Valve–Related Aortopathy.” All major aspects of bicuspid aortic valve aortopathy, including natural history, phenotypic expression, histology and molecular pathomechanisms, imaging, indications for surgery, surveillance, and follow-up, and recommendations for future research are contained within these guidelines. The current executive summary serves as a condensed version of the guidelines to provide clinicians with a current and comprehensive review of bicuspid aortic valve aortopathy and to guide the daily management of these complex patients.
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