Levels of sociality in nature vary widely. Some species are solitary; others live in family groups; some form complex multi-family societies. Increased levels of social interaction can allow for the ...spread of useful innovations and beneficial information, but can also facilitate the spread of harmful contagions, such as infectious diseases. It is natural to assume that these contagion processes shape the evolution of complex social systems, but an explicit account of the dynamics of sociality under selection pressure imposed by contagion remains elusive. We consider a model for the evolution of sociality strategies in the presence of both a beneficial and costly contagion. We study the dynamics of this model at three timescales: using a susceptible-infectious-susceptible (SIS) model to describe contagion spread for given sociality strategies, a replicator equation to study the changing fractions of two different levels of sociality, and an adaptive dynamics approach to study the long-time evolution of the population level of sociality. For a wide range of assumptions about the benefits and costs of infection, we identify a social dilemma: the evolutionarily-stable sociality strategy (ESS) is distinct from the collective optimum-the level of sociality that would be best for all individuals. In particular, the ESS level of social interaction is greater (respectively less) than the social optimum when the good contagion spreads more (respectively less) readily than the bad contagion. Our results shed light on how contagion shapes the evolution of social interaction, but reveals that evolution may not necessarily lead populations to social structures that are good for any or all.
Objectives
We sought to study the impact of COVID‐19 pandemic on the presentation delay, severity, patterns of care, and reasons for delay among patients with ST‐elevation myocardial infarction ...(STEMI) in a non‐hot‐spot region.
Background
COVID‐19 pandemic has significantly reduced the activations for STEMI in epicenters like Spain.
Methods
From January 1, 2020, to April 15, 2020, 143 STEMIs were identified across our integrated 18‐hospital system. Pre‐ and post‐COVID‐19 cohorts were based on March 23rd, 2020, whenstay‐at‐home orders were initiated in Ohio. We used presenting heart rate, blood pressure, troponin, new Q‐wave, and left ventricle ejection fraction (LVEF) to assess severity. Duration of intensive care unit stay, total length of stay, door‐to‐balloon (D2B) time, and radial versus femoral access were used to assess patterns of care.
Results
Post‐COVID‐19 presentation was associated with a lower admission LVEF (45 vs. 50%, p = .015), new Q‐wave, and higher initial troponin; however, these did not reach statistical significance. Among post‐COVID‐19 patients, those with >12‐hr delay in presentation 31(%) had a longer average D2B time (88 vs. 53 min, p = .033) and higher peak troponin (58 vs. 8.5 ng/ml, p = .03). Of these, 27% avoided the hospital due to fear of COVID‐19, 18% believed symptoms were COVID‐19 related, and 9% did not want to burden the hospital during the pandemic.
Conclusions
COVID‐19 has remarkably affected STEMI presentation and care. Patients' fear and confusion about symptoms are integral parts of this emerging public health crisis.
The invited special lecture at the 76th Annual Scientific Meeting of the Japanese Circulation Society focused on the central role of inflammation in vascular injury and repair. Early studies ...pioneered the concept that mechanical injury, such as balloon angioplasty and endovascular stent deployment, elicits an inflammatory response from the vessel wall. This hypothesis was developed and substantiated at a time when the prevailing dogma viewed restenosis following angioplasty as a primarily proliferative smooth muscle cell disease. Antibody targeting of Mac-1 reduced leukocyte accumulation and limited neointimal formation following balloon injury or stent implantation. Genetic absence of Mac-1 resulted in diminished leukocyte accumulation and neointimal thickening after carotid artery injury in mice. In the course of those studies, our laboratory made fundamental discoveries regarding the mechanism of leukocyte recruitment at sites of vascular injury and identified platelet glycoprotein (GP) Ibα, a component of the GPIb-IX-V complex, as the previously unknown platelet counter-receptor for Mac-1. Follow-on studies have focused extensively on the structure, function, and signaling of the leukocyte integrin Mac-1. The binding site for GPIbα in Mac-1 has been mapped and subsequently showed that leukocyte engagement of platelet GPIbα via Mac-1 is critical not only for the biological response to vascular injury, but also for thrombosis, vasculitis, glomerulonephritis, and multiple sclerosis, thereby advancing the hypothesis that virtually all inflammation is platelet-dependent. Furthermore, ligand engagement of Mac-1 initiates a novel gene program that promotes inflammation by activating NFκB and downregulating the expression of the forkhead transcription factor Foxp1 that controls monocyte differentiation. Small molecule inhibitors of Mac-1 function have been pursued, including targeting of Mac-1-GPIbα binding or the downstream tyrosine kinase spleen tyrosine kinase. Drs Teruo Inoue, Koichi Node, Tatsuya Fukotomi, Masashi Sakuma, Toshifumi Morooka, and Kohsuke Nakajima, valued Japanese collaborators and post-doctoral fellows, have contributed enormously to these discoveries. (Circ J 2012; 76: 1811–1818)
Summary Background Angiotensin-receptor blockers (ARBs) are a widely used drug class approved for treatment of hypertension, heart failure, diabetic nephropathy, and, recently, for cardiovascular ...risk reduction. Experimental studies implicate the renin-angiotensin system, particularly angiotensin II type-1 and type-2 receptors, in the regulation of cell proliferation, angiogenesis, and tumour progression. We assessed whether ARBs affect cancer occurrence with a meta-analysis of randomised controlled trials of these drugs. Methods We searched Medline, Scopus (including Embase), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and the US Food and Drug Administration website for studies published before November, 2009, that included any of the seven currently available ARBs. Randomised controlled trials with an ARB given in at least one group, with a follow-up of at least 1 year, and that enrolled at least 100 patients were included. New-cancer data were available for 61 590 patients from five trials. Data on common types of solid organ cancers were available for 68 402 patients from five trials, and data on cancer deaths were available for 93 515 patients from eight trials. Findings Telmisartan was the study drug in 30 014 (85·7%) patients who received ARBs as part of the trials with new cancer data. Patients randomly assigned to receive ARBs had a significantly increased risk of new cancer occurrence compared with patients in control groups (7·2% vs 6·0%, risk ratio RR 1·08, 95% CI 1·01–1·15; p=0·016). When analysis was limited to trials where cancer was a prespecified endpoint, the RR was 1·11 (95% CI 1·04–1·18, p=0·001). Among specific solid organ cancers examined, only new lung-cancer occurrence was significantly higher in patients randomly assigned to receive ARBs than in those assigned to receive control (0·9% vs 0·7%, RR 1·25, 1·05–1·49; p=0·01). No statistically significant difference in cancer deaths was observed (1·8% vs 1·6%, RR 1·07, 0·97–1·18; p=0·183). Interpretation This meta-analysis of randomised controlled trials suggests that ARBs are associated with a modestly increased risk of new cancer diagnosis. Given the limited data, it is not possible to draw conclusions about the exact risk of cancer associated with each particular drug. These findings warrant further investigation. Funding None.
Inflammation and thrombosis occur together in many diseases. The leukocyte integrin Mac-1 (also known as integrin α
β
, or CD11b/CD18) is crucial for leukocyte recruitment to the endothelium, and ...Mac-1 engagement of platelet GPIbα is required for injury responses in diverse disease models. However, the role of Mac-1 in thrombosis is undefined. Here we report that mice with Mac-1 deficiency (Mac-1
) or mutation of the Mac-1-binding site for GPIbα have delayed thrombosis after carotid artery and cremaster microvascular injury without affecting parameters of haemostasis. Adoptive wild-type leukocyte transfer rescues the thrombosis defect in Mac-1
mice, and Mac-1-dependent regulation of the transcription factor Foxp1 contributes to thrombosis as evidenced by delayed thrombosis in mice with monocyte-/macrophage-specific overexpression of Foxp1. Antibody and small-molecule targeting of Mac-1:GPIbα inhibits thrombosis. Our data identify a new pathway of thrombosis involving leukocyte Mac-1 and platelet GPIbα, and suggest that targeting this interaction has anti-thrombotic therapeutic potential with reduced bleeding risk.
Accumulating evidence supports the importance of macrophage plasticity in a broad spectrum of biological processes operative in health and disease. A major locus of control regulating macrophage ...polarization is at the transcriptional level, and several major pathways have been elucidated in recent years. In this study, we identify the Kruppel-like transcription factor 6 (KLF6) as a molecular toggle controlling macrophage speciation. KLF6 expression was robustly induced by pro-inflammatory M1 stimuli (e.g. LPS and IFN-γ) and strongly suppressed by M2 stimuli (e.g. IL4 and IL-13) in human and murine macrophages. Gain- and loss-of-function studies suggest that KLF6 is required for optimal LPS-induced pro-inflammatory gene expression, acting cooperatively with NF-κB. Furthermore, KLF6 inhibits anti-inflammatory gene expression by negatively regulating peroxisome proliferator-activated receptor γ expression in macrophages. Collectively, these observations identify KLF6 as a novel transcriptional regulator of macrophage polarization.
Background: Macrophage polarization regulates human inflammatory disorders.
Results: KLF6 is a novel transcriptional regulator of macrophage polarization.
Conclusion: KLF6 regulates macrophage inflammatory gene expression by modulating functions of NF-κB and PPARγ.
Significance: Pharmacological agents that modulate KLF6 signaling may allow for therapeutic gain in the treatment of inflammatory disorders.
Objectives This study sought to investigate the frequency, predictors, and detailed qualitative and quantitative assessment of optical coherence tomography (OCT)-detected stent edge dissections. Its ...impact on subsequent management and clinical outcomes were also investigated. Background OCT is a high-resolution imaging modality that can lead to more frequent recognition and accurate assessment of vascular injuries during percutaneous coronary intervention (PCI). Methods From September 2010 to June 2011, all patients with OCT post-PCI were enrolled. Edge dissections were defined as disruptions of the arterial lumen surface in both the 5-mm distal and proximal stent edges. Qualitative and quantitative analyses of all edges were performed at 0.2-mm intervals. Results In total, 395 edges (249 lesions in 230 patients) were analyzed. The overall incidence of OCT-detected edge dissection was 37.8%, and most (84%) were not apparent on angiography. Independent predictors for OCT-detected dissections were presence of atherosclerotic plaque at stent edges, calcification angle, minimum fibrous cap thickness, thin-cap fibroatheromas, stent/lumen eccentricity, and vessel overstretching. Mean dissection length measured 2.04 ± 1.60 mm, 96.2% appeared as flaps, and 52.8% extended beyond the intima/atheroma layer. Additional stenting was performed in 22.6% of all dissections, which were longer, had bigger dimensions, and promoted deeper vascular injury. The 12-month major adverse cardiac event rate was similar between patients with (7.95%) and without (5.69%, p = 0.581) dissections. Conclusions High rates of stent edge dissections were detected by OCT, usually related to the presence of atherosclerosis at stent edges and to PCI technique. Detailed OCT assessment of dissection severity was possible and affected the subsequent management of this complication. Non–flow-limiting, small, and superficial dissections left untreated proved benign.
Context
The global drylands cover 41% of the terrestrial surface and support millions of pastoralists and host diverse flora and fauna. Ongoing socioeconomic and environmental transformations in ...drylands make it imperative to understand how to achieve the twin goals of food security and ecosystem health.
Objectives
The review focuses on examining the patterns of rangeland vegetation dynamics and livelihood transformations associated with changes in pastoralist mobility.
Methods
We conducted a comprehensive review of literature on dryland sustainability based on the coupled systems framework and through the lens of mobility, which reflects not only human and livestock movements but also the unique lifestyles and cultural identities of people in drylands.
Results
We find that mobility, which is critical for pastoralists to survive and thrive in the drylands, is generally in decline and has significant implications on dryland sustainability. Reduced mobility exacerbates bush encroachment and land degradation, as sedentarized pastoralists use the rangelands more recursively. Associated with declining mobility is livelihood intensification and diversification, but such livelihood transitions may carry both socioeconomic and environmental risks.
Conclusions
We argue that to advance landscape sustainability science and reconcile concerns over environmental conservation and human well-being across the global drylands, we must better understand the underlying mechanisms of coupled systems transitions through the lens of mobility, and integrate the perspectives of multiple stakeholders with fundamentally different interests and priorities.
Background Cardiac resynchronization therapy (CRT) is effective in reducing clinical events in systolic heart failure patients with a wide QRS. Previous retrospective studies suggest only patients ...with QRS prolongation due to a left bundle-branch block (LBBB) benefit from CRT. Our objective was to examine this by performing a meta-analysis of all randomized controlled trials of CRT. Methods Systematic searches of MEDLINE and the Food and Drug Administration official website were conducted for randomized controlled CRT trials. Trials reporting adverse clinical events (eg, all-cause mortality, heart failure hospitalizations) according to QRS morphology were included in the meta-analysis. Results Four randomized trials totaling 5,356 patients met the inclusion criteria. In patients with LBBB at baseline, there was a highly significant reduction in composite adverse clinical events with CRT (RR = 0.64 95% CI (0.52-0.77), P = .00001). However no such benefit was observed for patients with non-LBBB conduction abnormalities (RR = 0.97 95% CI (0.82-1.15), P = .75). When examined separately, there was no benefit in patients with right-bundle branch block (RR = 0.91 95% CI (0.69-1.20), P = .49) or non-specific intraventricular conduction delay (RR = 1.19 95% CI (0.87-1.63), P = .28). There was no heterogeneity among the clinical trials with regards to the lack of benefit in non-LBBB patients ( I2 = 0%). When directly compared, the difference in effect of CRT between LBBB versus non-LBBB patients was highly statistically significant ( P = .0001 by heterogeneity analysis). Conclusions While CRT was very effective in reducing clinical events in patients with LBBB, it did not reduce such events in patients with wide QRS due to other conduction abnormalities.
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