Fractal Markets Hypothesis and the Global Financial Crisis: Scaling, Investment Horizons and Liquidity

We investigate whether fractal markets hypothesis and its focus on liquidity and invest- ment horizons give reasonable predictions about dynamics of the financial markets during the turbulences such as the Global Financial Crisis of late 2000s. Compared to the mainstream efficient markets hypothesis, fractal markets hypothesis considers financial markets as com- plex systems consisting of many heterogenous agents, which are distinguishable mainly with respect to their investment horizon. In the paper, several novel measures of trading activity at different investment horizons are introduced through scaling of variance of the underlying processes. On the three most liquid US indices - DJI, NASDAQ and S&P500 - we show that predictions of fractal markets hypothesis actually fit the observed behavior quite well.Comment: 11 pages, 3 figure

Impact of a multidisciplinary approach in enteropathic spondyloarthritis patients

Spondyloarthritis (SpA) and inflammatory bowel disease (IBD) are chronic autoinflammatory diseases that partially share the genetic predisposition and the unchecked inflammatory response linking the gut to the joints. The coexistence of both conditions in patients and the increased cross-risk ratios between SpA and IBD strongly suggest a shared pathophysiology. The prevalence of Enteropathic-related Spondyloarthritis (ESpA) in IBD patients shows a wide variation and may be underestimated. It is well accepted that the management of joint pain requires rheumatological expertise in conjunction with gastroenterologist assessment. In this view, we aimed at assessing, in a prospective study performed in a combined Gastro-Intestinal and Rheumatologic "GI-Rhe" clinic: (1) the prevalence of ESpA and other rheumatologic diseases in IBD patients with joint pain; (2) the features of the ESpA population; and (3) the diagnostic delay and the potential impact of the combined assessment. From November 2012 to December 2014, IBD patients with joint pain referring to a dedicated rheumatologist by the IBD-dedicated gastroenterologist were enrolled. Clinical and biochemical evaluations, joint involvement and disease activity assessment, diagnostic delay, and treatment were recorded. IBD patients (n = 269) with joint pain were jointly assessed in the "GI-Rhe" Unit. A diagnosis of ESpA was made in 50.5% of IBD patients with joint pain. ESpA patients showed a peripheral involvement in 53% of cases, axial in 20.6% and peripheral and axial in 26.4% of cases. ESpA patients had a higher prevalence of other autoimmune extra-intestinal manifestations and received more anti-TNF treatment compared with IBD patients. A mean diagnostic delay of 5.2. years was revealed in ESpA patients. Patients with joint disease onset in the 2002-2012 decade had reduced diagnostic delay compared with those with onset in the 1980-1990 and 1991-2001 decades. Diagnostic delay was further reduced for patients with joint onset in the last two years in conjunction with the establishment of the GI-Rhe clinic. Multidisciplinary approach improved management of rheumatic disorders in IBD patients allowing a more comprehensive care

The real effects of banking supervision: Evidence from enforcement actions

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordWe present a novel way to examine macro-financial linkages by focusing on the real effects of bank supervisors’ enforcement actions. Exploiting plausibly exogenous variation in supervisory monitoring intensity, we show that enforcement actions in single-market banks trigger temporarily large adverse effects for the macroeconomy by reducing personal income growth, the number of establishments, and increasing unemployment. These effects are related to contractions in bank lending and liquidity creation, and are more pronounced when we consider enforcement actions on both single-market and multi-market banks, and in counties with fewer banks and greater external financial dependence

A systematic review of care pathways for psychosis in low-and middle-income countries

Pathways to care for psychosis in high-income countries have been well studied, with the finding of an association between longer duration of untreated psychosis (DUP) and poorer outcomes focusing interest on care pathways to minimise treatment delay. Little is known about how people with psychosis in low-to middle-income countries (LMIC) present for help and specific care pathways that might be associated with treatment delays in those contexts. We conducted a systematic review using electronic databases (MEDLINE, PsychINFO, Embase, Ovid) to explore what proportion of patients with psychosis in LMIC are accessing care through traditional healers and whether this is associated with treatment delay. Studies were included if they assessed the pathway to care for participants with a psychotic illness in a LMIC. From 3929 results, 15 studies met our inclusion criteria. In 7 out of 15 studies first contact for the majority of patients were traditional health practitioners (THPs). In 5 out of 15 studies, mental health practitioners (MHPs) were most often the initial care pathway and in 3 studies first contact was with primary care. DUP ranged from a mean of 30 weeks to 225 weeks. Accessing THPs as initial contact was associated with a longer DUP. In LMICs, a large proportion of patients use THP as their first point of contact for accessing care. This is associated with longer DUP. Services in these countries need to focus both on raising public awareness and collaborative working with THPs to facilitate access to biomedical care

Wireless capsule endoscopy and proximal small bowel lesions in Crohn's disease

AIM: To investigate the prevalence of proximal small bowel (SB) lesions detected by wireless capsule endoscopy (WCE) in Crohn's disease (CD). METHODS: WCE was performed in 64 patients: 32 with CD of the distal ileum, and 32 controls with iron-deficiency anemia (IDA) or diarrhea. WCE was performed using the Given SB-WCE, followed by small intestine contrast ultrasonography (SICUS). Findings compatible with CD by using WCE included erosions, aphthoid or deep ulcers, and strictures/stenosis. RESULTS: WCE detected proximal SB lesions in 16/32 (50%) patients (14 aphthoid ulcers, 2 deep ulcers, one stricture), which appeared not to be related to clinical parameters [epigastric pain, age, smoking, non-steroidal anti-inflammatory drugs (NSAIDs), IDA]. Among patients with proximal SB lesions, 6 (37%) were smokers, 3 (19%) NSAID users, 3 (19%) had epigastric pain and 4 (25%) had IDA. SICUS detected proximal SB lesions in 3/32 patients (19%) also showing lesions with WCE. No correlations were observed between proximal SB lesions assessed by WCE or by SICUS (χ2 = 1.5, P = 0.2). CONCLUSION: The use of WCE allows the detection of previously unknown upper SB lesions in a high proportion of patients with a previous diagnosis of CD involving the distal ileum. © 2010 Baishideng

Identification of new benzofuran derivatives as STING agonists with broad-spectrum antiviral activity

The Stimulator of Interferon Genes (STING) is involved in cytosolic DNA sensing and type I Interferons (IFN-I) induction. Aiming to identify new STING agonists with antiviral activity and given the known biological activity of benzothiazole and benzimidazole derivatives, a series of benzofuran derivatives were tested for their ability to act as STING agonists, induce IFN-I and inhibit viral replication. Compounds were firstly evaluated in a gene reporter assay measuring luciferase activity driven by the human IFN-β promoter in cells expressing exogenous STING (HEK293T). Seven of them were able to induce IFN-β transcription while no induction of the IFN promoter was observed in the presence of a mutated and inactive STING, showing specific protein-ligand interaction. Docking studies were performed to predict their putative binding mode. The best hit compounds were then tested on human coronavirus 229E replication in BEAS-2B and MRC-5 cells and three derivatives showed EC50 values in the μM range. Such compounds were also tested on SARS-CoV-2 replication in BEAS-2B cells and in Calu-3 showing they can inhibit SARS-CoV-2 replication at nanomolar concentrations. To further confirm their IFN- dependent antiviral activity, compounds were tested to verify their effect on phospho-IRF3 nuclear localization, that was found to be induced by benzofuran derivatives, and SARS-CoV-2 replication in Vero E6 cells, lacking IFN production, founding them to be inactive. In conclusion, we identified benzofurans as STING- dependent immunostimulatory compounds and host-targeting inhibitors of coronaviruses representing a novel chemical scaffold for the development of broad-spectrum antivirals

TRAF3IP2 gene is associated with cutaneous extraintestinal manifestations in Inflammatory bowel disease

Background and aims: Genome-wide association (GWA) studies recently identified a novel gene, TRAF3IP2, involved in the susceptibility to psoriasis. Common immune-mediated mechanisms involving the skin or the gut have been suggested. We therefore aimed to assess the role of TRAF3IP2 gene in IBD, with particular regard to the development of cutaneous extraintestinal manifestations (pyoderma gangrenosum, erythema nodosum). The association with psoriasis was also assessed in a secondary analysis. Methods: The analysis included 267 Crohn's disease (CD), 200 ulcerative colitis (UC) patients and 278 healthy controls. Three TRAF3IP2 SNPs were genotyped by allelic discrimination assays. A case/control association study and a genotype/phenotype correlation analysis have been performed. Results: All three SNPs conferred a high risk to develop cutaneous manifestations in IBD. A higher risk of pyoderma gangrenosum and erythema nodosum was observed in CD patients carrying the Rs33980500 variant (OR 3.03; P=0.026)In UC, a significantly increased risk was observed for both the Rs13190932 and the Rs13196377 SNPs (OR 5.05; P=0.02 and OR 4.1; P=0.049). Moreover, association of TRAF3IP2 variants with ileal (OR = 1.92), fibrostricturing (OR = 1.91) and perianal CD (OR = 2.03) was observed. Conclusions: This is the first preliminary report indicating that TRAF3IP2 variants increase the risk of cutaneous extraintestinal manifestations in IBD suggesting that the analysis of the TRAF3IP2 variants may be useful for identifying IBD patients at risk to develop these manifestations. © 2012 European Crohn's and Colitis Organisation

Direct-acting antivirals used in HCV-related liver disease do not affect thyroid function and autoimmunity

Purpose It is well known that interferon-alpha (IFN-alpha), used for long time as the main therapy for HCV-related disease, induces thyroid alterations, but the impact of the new direct-acting antivirals (DAAs) on thyroid is not established. Aim of this prospective study was to evaluate if DAAs therapy may induce thyroid alterations.Methods A total of 113 HCV patients, subdivided at the time of the enrollment in naive group (n = 64) and in IFN-alpha group (n = 49) previously treated with pegylated interferon-alpha and ribavirin, were evaluated for thyroid function and autoimmunity before and after 20-32 weeks of DAAs.Results Before starting DAAs, a total of 8/113 (7.1%) patients showed Hashimoto's thyroiditis (HT) all belonging to IFN-alpha group (8/49, 16.3%), while no HT cases were found in the naive group. Overall, 7/113 (6.2%) patients were hypothyroid: 3/64 (4.7%) belonging to naive group and 4/49 (8.2%) to IFN-alpha group. Furthermore, a total of 8/113 patients (7.1%) showed subclinical hyperthyroidism: 2/64 (3.1%) were from naive group and 6/49 (12.2%) from IFN-alpha group. Interestingly, after DAAs therapy, no new cases of HT, hypothyroidism and hyperthyroidism was found in all series, while 6/11 (54.5%) patients with non-autoimmune subclinical thyroid dysfunction became euthyroid. Finally, the only association between viral genotypes and thyroid alterations was genotype 1 and hypothyroidism.Conclusions This study supports evidence that DAAs have a limited or missing influence on thyroid in patients with HCV-related diseases. Moreover, it provides preliminary evidence that subclinical non-autoimmune thyroid dysfunction may improve after HCV infection resolution obtained by DAAs

Pragmatic Trial Design to Compare Real-world Effectiveness of Different Treatments for Inflammatory Bowel Diseases: The PRACTICE-IBD European Consensus

background and aims: pragmatic studies designed to test interventions in everyday clinical settings can successfully complement the evidence from registration and explanatory clinical trials. the european consensus project PRACTICE-IBD was developed to identify essential criteria and address key methodological issues needed to design valid, comparative, pragmatic studies in inflammatory bowel diseases [BDs]. methods: statements were issued by a panel of 11 european experts in IBD management and trial methodology, on four main topics: [I] study design; [II] eligibility, recruitment and organisation, flexibility; [III] outcomes; [IV] analysis. the consensus process followed a modified delphi approach, involving two rounds of assessment and rating of the level of agreement [1 to 9; cut-off ≥7 for approval] with the statements by 18 additional european experts in IBD. results: at the first voting round, 25 out of the 26 statements reached a mean score ≥7. following the discussion that preceded the second round of voting, it was decided to eliminate two statements and to split one into two. at the second voting round, 25 final statements were approved: seven for study design; six for eligibility, recruitment and organisation, flexibility; eight for outcomes; and four for analysis. conclusions: pragmatic, randomised, clinical trials can address important questions in IBD clinical practice, and may provide complementary, high-level evidence, as long as they follow a methodologically rigorous approach. these 25 statements intend to offer practical guidance in the design of high-quality, pragmatic, clinical trials that can aid decision making in choosing a management strategy for IBDs

Safety of treatments for inflammatory bowel disease: Clinical practice guidelines of the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD)

Inflammatory bowel diseases are chronic conditions of unknown etiology, showing a growing incidence and prevalence in several countries, including Italy. Although the etiology of Crohn's disease and ulcerative colitis is unknown, due to the current knowledge regarding their pathogenesis, effective treatment strategies have been developed. Several guidelines are available regarding the efficacy and safety of available drug treatments for inflammatory bowel diseases. Nevertheless, national guidelines provide additional information adapted to local feasibility, costs and legal issues related to the use of the same drugs. These observations prompted the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) to establish Italian guidelines on the safety of currently available treatments for Crohn's disease and ulcerative colitis. These guidelines discuss the use of aminosalicylates, systemic and low bioavailability corticosteroids, antibiotics (metronidazole, ciprofloxacin, rifaximin), thiopurines, methotrexate, cyclosporine A, TNFα antagonists, vedolizumab, and combination therapies. These guidelines are based on current knowledge derived from evidence-based medicine coupled with clinical experience of a national working group