Controlling Financial Chaos: The Power and Limits of Law

This Essay examines how law can help to control financial chaos. To that end, regulation should strive to not only maximize economic efficiency within the financial system but also protect the financial system itself. Any regulatory framework for achieving these goals, however, will be imperfect and have tradeoffs. Increasing financial complexity has created information failures that even disclosure cannot remedy, whereas law-imposed standardization would have its own flaws. Bounded human rationality limits the effectiveness of even otherwise ideal laws. Furthermore, the increasing dispersion of financial risk is undermining monitoring incentives. We also do not yet fully understand how systemic risk is triggered and spread. Because regulation therefore cannot prevent systemic shocks, regulation should also operate to reduce systemic consequences by stabilizing parts of the financial system afflicted by those shocks

Plasma total antioxidant capacity and peroxidation biomarkers in psoriasis

Systemic biomarkers of oxidative stress can be relevant for assessment of psoriasis severity, for prediction of the outcome of therapy and of the development of comorbidities. In this review we aimed to evaluate the relationship between plasma total antioxidant capacity (TAC) and peroxidation biomarkers, as well as their association with dyslipidemia and systemic inflammation in psoriasis. The review of 59 case–control comparisons (from 41 studies) and 17 interventions (from 13 studies) suggests that peroxidation markers are more sensitive than TAC in the evaluation of oxidative stress in psoriasis. Although few studies investigated the effect of treatment on oxidative stress, it seems that biological drugs could be the better choice in the treatment of psoriasis. However, considering the limitations of TAC and plasma peroxidation markers, this review suggests that new methods should be developed in order to evaluate systemic oxidative stress in psoriasis

Major Outcomes in Atrial Fibrillation Patients with One Risk Factor: Impact of Time in Therapeutic Range

BACKGROUND: The benefits and harms of oral anticoagulation (OAC) therapy in patients with only one stroke risk factor (i.e. CHA2DS2-VASc= 1 in males, or 2 in females) has been subject of debate. METHODS: We analysed all patients with only one stroke risk factor from the merged datasets of SPORTIF III and V trials. Anticoagulation control was defined according to time in therapeutic range (TTR). RESULTS: Of the original trial cohort, 1,097 patients had only one stroke risk factor. Stroke/systemic thromboembolic event had an incidence of 0.9 per 100 patient-years, with an incidence of 1.6 per 100 patient-years for all-cause death and 2.3%/patient-years for the composite outcome of stroke/systemic thromboembolic event/all-cause death. There were no significant differences in the risk for stroke/systemic thromboembolic event between sexes, nor between the different stroke risk factors amongst these atrial fibrillation patients with only one stroke risk factor. Cox regression analysis in patients treated with warfarin only found TTR to be inversely associated with stroke/systemic thromboembolic event (p=0.034) and all-cause death (p=0.015). Chronic heart failure was significantly associated with the outcome of all-cause death (p=0.0019) and the composite outcome of stroke/systemic thromboembolic event/all-cause death (p=0.021). There was a significant inverse linear association between TTR and the cumulative risk for both stroke/systemic thromboembolic event and all-cause death (both p<0.001). CONCLUSIONS: In atrial fibrillation patients with only one additional stroke risk factor (i.e. CHA2DS2-VASc= 1 in males or 2 in females), rates of major adverse events (stroke/systemic thromboembolic event, mortality) were high, despite anticoagulation. TTR in warfarin-treated patients was inversely associated with the occurrence of both stroke/systemic thromboembolic event and all-cause death

Oral tolerance to cancer can be abrogated by T regulatory cell inhibition

Oral administration of tumour cells induces an immune hypo-responsiveness known as oral tolerance. We have previously shown that oral tolerance to a cancer is tumour antigen specific, non-cross-reactive and confers a tumour growth advantage. We investigated the utilisation of regulatory T cell (Treg) depletion on oral tolerance to a cancer and its ability to control tumour growth. Balb/C mice were gavage fed homogenised tumour tissue – JBS fibrosarcoma (to induce oral tolerance to a cancer), or PBS as control. Growth of subcutaneous JBS tumours were measured; splenic tissue excised and flow cytometry used to quantify and compare systemic Tregs and T effector (Teff) cell populations. Prior to and/or following tumour feeding, mice were intraperitoneally administered anti-CD25, to inactivate systemic Tregs, or given isotype antibody as a control. Mice which were orally tolerised prior to subcutaneous tumour induction, displayed significantly higher systemic Treg levels (14% vs 6%) and faster tumour growth rates than controls (p<0.05). Complete regression of tumours were only seen after Treg inactivation and occurred in all groups - this was not inhibited by tumour feeding. The cure rates for Treg inactivation were 60% during tolerisation, 75% during tumour growth and 100% during inactivation for both tolerisation and tumour growth. Depletion of Tregs gave rise to an increased number of Teff cells. Treg depletion post-tolerisation and post-tumour induction led to the complete regression of all tumours on tumour bearing mice. Oral administration of tumour tissue, confers a tumour growth advantage and is accompanied by an increase in systemic Treg levels. The administration of anti-CD25 Ab decreased Treg numbers and caused an increase in Teffs. Most notably Treg cell inhibition overcame established oral tolerance with consequent tumor regression, especially relevant to foregut cancers where oral tolerance is likely to be induced by the shedding of tumour tissue into the gut

UK Foot and Mouth disease: a systemic risk assessment of existing controls

This article details a systemic analysis of the controls in place and possible interventions available to further reduce the risk of a foot and mouth disease (FMD) outbreak in the United Kingdom. Using a research-based network analysis tool, we identify vulnerabilities within the multibarrier control system and their corresponding critical control points (CCPs). CCPs represent opportunities for active intervention that produce the greatest improvement to United Kingdom's resilience to future FMD outbreaks. Using an adapted ‘features, events, and processes’ (FEPs) methodology and network analysis, our results suggest that movements of animals and goods associated with legal activities significantly influence the system's behavior due to their higher frequency and ability to combine and create scenarios of exposure similar in origin to the U.K. FMD outbreaks of 1967/8 and 2001. The systemic risk assessment highlights areas outside of disease control that are relevant to disease spread. Further, it proves to be a powerful tool for demonstrating the need for implementing disease controls that have not previously been part of the system

A systematic review and meta-analysis of systemic intraoperative anticoagulation during arteriovenous access formation for dialysis

Purpose: Surgical arteriovenous fistula (AVF) or graft (AVG) is preferred to a central venous catheter for dialysis access. Surgical access may suffer thrombosis early after placement and systemic anticoagulation during surgical access formation may increase patency rates but would be expected to increase bleeding-related complications. A systematic review and meta-analysis of randomised controlled trials was conducted to examine the impact of systemic anticoagulation on access surgery perioperative bleeding and patency rates. Methods: We included randomised controlled trials testing systemic anticoagulation during access formation versus a control group without systemic anticoagulation reporting bleeding complications and access patency. Medline, Embase, CENTRAL and CINAHL were searched up to March 2015. Risk of bias was assessed using the Cochrane risk of bias tool and the Jadad score. Meta-analysis was performed using Cochrane Revman ® software. Results: Searches identified 445 reports of which four randomised studies involving 411 participants were included. Three studies pertained to AVF only and one included both AVF and AVG. Systemic anticoagulation led to increased bleeding events in all access [four trials; risk ratio (RR) 7.18; confidence interval (CI), 2.41 to 21.38; p < 0.001]. Patency was not improved for all access (four trials; RR, 0.64; CI, 0.37 to 1.09; p = 0.10) but was improved when AVF analysed alone (three trials; RR, 0.57; CI, 0.33 to 0.97; p = 0.04). Conclusions: The use of intraoperative systemic anticoagulation during access formation is associated with a highly significant increased risk of bleeding-related complications. A significant improvement in AVF patency was seen, though not when AVF and AVG were analysed together

It takes two to tango: NAD+ and sirtuins in aging/longevity control

AbstractThe coupling of nicotinamide adenine dinucleotide (NAD+) breakdown and protein deacylation is a unique feature of the family of proteins called ‘sirtuins.’ This intimate connection between NAD+ and sirtuins has an ancient origin and provides a mechanistic foundation that translates the regulation of energy metabolism into aging and longevity control in diverse organisms. Although the field of sirtuin research went through intensive controversies, an increasing number of recent studies have put those controversies to rest and fully established the significance of sirtuins as an evolutionarily conserved aging/longevity regulator. The tight connection between NAD+ and sirtuins is regulated at several different levels, adding further complexity to their coordination in metabolic and aging/longevity control. Interestingly, it has been demonstrated that NAD+ availability decreases over age, reducing sirtuin activities and affecting the communication between the nucleus and mitochondria at a cellular level and also between the hypothalamus and adipose tissue at a systemic level. These dynamic cellular and systemic processes likely contribute to the development of age-associated functional decline and the pathogenesis of diseases of aging. To mitigate these age-associated problems, supplementation of key NAD+ intermediates is currently drawing significant attention. In this review article, we will summarize these important aspects of the intimate connection between NAD+ and sirtuins in aging/longevity control.</jats:p

Insights on adaptive and innate immunity in canine leishmaniosis

Canine leishmaniosis (CanL) is caused by the parasite Leishmania infantum and is a systemic disease, which can present with variable clinical signs, and clinicopathological abnormalities. Clinical manifestations can range from subclinical infection to very severe systemic disease. Leishmaniosis is categorized as a neglected tropical disease and the complex immune responses associated with Leishmania species makes therapeutic treatments and vaccine development challenging for both dogs and humans. In this review, we summarize innate and adaptive immune responses associated with L. infantum infection in dogs, and we discuss the problems associated with the disease as well as potential solutions and the future direction of required research to help control the parasite