A hard nut to crack : regulatory failure shows how rating really works

Credit rating agencies such as Moody’s and Standard & Poor’s are key players in the governance of global financial markets. Given the very strong criticism the rating agencies faced in the wake of the global financial crisis 2008, how can we explain the puzzle of their survival? Market and regulatory reliance on ratings continues, despite the shift from a light-touch to a mandatory system of agency regulation and supervision. Drawing on the analysis of rating agency regulation in the US and the EU before and after the financial crisis, we argue that a pervasive, persistent and, in our view, erroneous understanding of rating has supported the never-ending story of rating agency authority. We show how treating ratings as metrics, private goods, and independent and neutral third-party opinions contributes to the ineffectiveness of rating agency regulation and supports the continuing authoritative standing of the credit rating agencies in market and regulatory practices

Sex-related Differences in Systemic Sclerosis: A Multicenter Cross-sectional Study From the National Registry of the Italian Society for Rheumatology

OBJECTIVE: There is still a great deal to learn about the influence of sex in systemic sclerosis (SSc). In this respect, national registries provide large and homogeneous patient cohorts for analytical studies. We therefore investigated a wide-ranging and well-characterized SSc series with the aim of identifying sex differences in disease expression, with a special focus on demographic, clinical, and serological characteristics. METHODS: A multicenter SSc cohort of 2281 patients, including 247 men, was recruited in the Italian Systemic sclerosis PRogression INvestiGation (SPRING) registry. Demographic data, disease manifestations, serological profile, and internal organ involvement were compared. RESULTS: The overall female/male ratio was 8.2:1. Female/male ratios for limited cutaneous SSc, diffuse cutaneous SSc, and SSc sine scleroderma subsets were 8.7:1, 4.9:1, and 10.7:1, respectively. A shorter time from onset of Raynaud phenomenon to SSc diagnosis, an increased prevalence of the diffuse cutaneous subset, renal crisis, and digital ulcers were found in males, whereas a significantly higher percentage of sicca syndrome, serum antinuclear antibodies, antiextractable nuclear antigens, anti-La/SSB, and anticentromere protein B was detected in the female group. Males exhibited lower left ventricular ejection fraction, as well as higher prevalence of conduction blocks, arrhythmias, ground glass, and honeycombing. Moreover, forced vital capacity and total lung capacity were medially lower in men than in women. Finally, males were more frequently treated with immunosuppressive drugs. CONCLUSION: Our study further supports the presence of several sex-related differences in patients with SSc. These differences were pronounced in the severity of cutaneous, peripheral vascular, and cardiopulmonary involvement for male patients, whereas an increased prevalence of sicca syndrome and a specific autoantibody profile characterized the female sex

Geographical heterogeneity of clinical and serological phenotypes of systemic sclerosis observed at tertiary referral centres. The experience of the Italian SIR-SPRING registry and review of the world literature

Introduction: Systemic sclerosis (SSc) is characterized by a complex etiopathogenesis encompassing both host genetic and environmental -infectious/toxic- factors responsible for altered fibrogenesis and diffuse microangiopathy. A wide spectrum of clinical phenotypes may be observed in patients' populations from different geographical areas. We investigated the prevalence of specific clinical and serological phenotypes in patients with definite SSc enrolled at tertiary referral centres in different Italian geographical macro-areas. The observed findings were compared with those reported in the world literature.Materials and methods: The clinical features of 1538 patients (161 M, 10.5%; mean age 59.8 +/- 26.9 yrs.; mean disease duration 8.9 +/- 7.7 yrs) with definite SSc recruited in 38 tertiary referral centres of the SPRING (Systemic sclerosis Progression INvestiGation Group) registry promoted by Italian Society of Rheumatology (SIR) were obtained and clustered according to Italian geographical macroareas.Results: Patients living in Southern Italy were characterized by more severe clinical and/or serological SSc phenotypes compared to those in Northern and Central Italy; namely, they show increased percentages of diffuse cutaneous SSc, digital ulcers, sicca syndrome, muscle involvement, arthritis, cardiopulmonary symptoms, interstitial lung involvement at HRCT, as well increased prevalence of serum anti-Scl70 autoantibodies. In the same SSc population immunusppressive drugs were frequently employed. The review of the literature underlined the geographical heterogeneity of SSc phenotypes, even if the observed findings are scarcely comparable due to the variability of methodological approaches.Conclusion: The phenotypical differences among SSc patients' subgroups from Italian macro-areas might be correlated to genetic/environmental co-factors, and possibly to a not equally distributed national network of information and healthcare facilities

High prevalence of metabolic syndrome in patients with ankylosing spondylitis.

The objective of this work is to investigate the occurrence of atherosclerosis and metabolic syndrome (MetS) in ankylosing spondylitis (AS) patients (pts). Twenty-four consecutive AS pts (men, 87.5%; median age, 50.5 years; median disease duration, 16.5 years), fulfilling the modified 1984 New York criteria for AS criteria, and 19 age- and sexmatched controls were investigated. Clinical atherosclerosis was evaluated by physical examination for cardiovascular (CV) diseases and history or drug use for CV events. Subclinical atherosclerosis was detected by mean intima media thickness (a-IMT) and maximum IMT (max-IMT) of carotid arteries using ultrasonography. Laboratory investigations including fasting plasma glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides were assessed by standard methods, while homocysteine was assessed by chemiluminescence. MetS was assessed using the updated NCEP-ATP III criteria. Disease activity was defined according to the International Ankylosing Spondylitis Assessment Study criteria. The 10-year CV risk (%) profile was evaluated in agreement to the Progetto Cuore criteria. No major CV event was detected in the study population. No significant differences were found when AS pts and controls were compared according to the mean a-IMT (0.52±0.26 vs 0.51±0.13 mm), max-IMT (0.92±0.20 vs 0.85±0.39 mm), prevalence of abnormal max-IMT >1 mm (27.2 vs 5.3%), and 10-year CV risk (9.9±9.6 vs 3.6±1.8%). Systolic blood pressure (p=0.04), triglyceride to HDL cholesterol ratio (p=0.002), and LDL cholesterol (p=0.03) were found significantly higher in AS pts than in controls; on the contrary, HDL cholesterol was pointed out as significantly lower (p<0.001). MetS was found in 11/24 (45.8%) AS pts and in 2/19 (10.5%) controls (p=0.019). No significant relationship emerged in MetS prevalence among AS pts regarding the mean value of age, disease duration, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Disease Activity Index, and the Italian version of Health Assessment Questionnaire. This preliminary report points out a higher prevalence of MetS in AS pts than in controls. Further studies are needed to confirm this finding

ECOTOXICITY OF KETOPROFEN AND THE S(+)-ENANTIOMER (DEXKETOPROFEN): BIOASSAYS IN FRESHWATER MODEL SPECIES AND RESPONSES OF FISH PLHC-1 CELL-LINE

The ecotoxicological properties of ketoprofen (KP) or its enantiomer (dexketoprofen: DKP) in different experimental models were evaluated. Firstly, by acute and chronic toxicity tests using three representative model organisms (Vibrio fischeri, Pseudokirchneriella subcapitata and Ceriodaphnia dubia). Secondly, by evaluating the responses of biotransformation systems and multidrug resistance associated proteins (MRP1/MRP2) using the PLHC-1 fish hepatic cell-line. Data from both acute and chronic exposure of model organisms showed that DKP produced an higher toxicity (inhibition of bioluminescence and algal growth and crustacean mortality/immobilization), compared to KP; however effects were detectable only at high concentrations. The growth inhibition test with P. subcapitata showed that KP and DKP exhibited different values for the no observable effect concentration (NOEC) and lowest observable effect concentration (LOEC). Further, KP and DKP did not exert cytotoxic effects in PLHC-1 cells, showing compound-, time- and dose-dependent differential effects on phase I and II biotransformation systems. For CYP1A, cell exposure to KP and DKP differed at transcript and activity levels. Exposure to KP and DKP modulated MRP1 and MRP2 mRNA levels and these effects were also compound-, time- and dose-dependent. Overall, the present study revealed the interactions between these compounds and key detoxification systems, and different sensitivity to the racemic KP mixture compared to its S(+) enantiomer (DKP)

Vitamin D deficiency in systemic sclerosis: a possible role of subclinical liver fibrosis? Retrospective analysis from an Italian cohort

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Vitamin D deficiency in systemic sclerosis: a possible role of subclinical liver fibrosis? Retrospective analysis from an Italian cohort

Vitamin D deficiency in systemic sclerosis: a possible role of subclinical liver fibrosis? Retrospective analysis from an Italian cohor

UCLA Scleroderma Clinical Trials Consortium Gastrointestinal Tract (GIT) 2.0 Reflux Scale Correlates With Impaired Esophageal Scintigraphy Findings in Systemic Sclerosis

Objective The University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 (GIT 2.0) instrument is a self-report tool measuring gastrointestinal (GI) quality of life in patients with systemic sclerosis (SSc). Scarce data are available on the correlation between patient-reported GI symptoms and motility dysfunction as assessed by esophageal transit scintigraphy (ETS). Methods We evaluated the GIT 2.0 reflux scale in patients with SSc admitted to our clinic and undergoing ETS, and correlated their findings. Results Thirty-one patients with SSc undergoing ETS were included. Twenty-seven were female, and 9 had diffuse cutaneous SSc. Twenty-six of 31 (84%) patients had a delayed transit and an abnormal esophageal emptying activity (EA); they also had a higher GIT 2.0 reflux score (P = 0.04). Mean EA percentage was higher in patients with none to mild GIT 2.0 reflux score (81.1 [SD 11.5]) than in those with moderate (55.7 [SD 17.8], P = 0.003) and severe to very severe scores (55.8 [SD 19.7], P = 0.002). The percentage of esophageal EA negatively correlated with the GIT 2.0 reflux score (r = –0.68, P < 0.0001), but it did not correlate with the other GIT 2.0 scales and the total GIT 2.0 score. Conclusion SSc patients with impaired ETS findings have a higher GIT 2.0 reflux score. The GIT 2.0 is a complementary tool for objective measurement of esophageal involvement that can be easily administered in day-to-day clinical assessment