A blue sky catastrophe in double-diffusive convection

A global bifurcation of the blue sky catastrophe type has been found in a small Prandtl number binary mixture contained in a laterally heated cavity. The system has been studied numerically applying the tools of bifurcation theory. The catastrophe corresponds to the destruction of an orbit which, for a large range of Rayleigh numbers, is the only stable solution. This orbit is born in a global saddle-loop bifurcation and becomes chaotic in a period doubling cascade just before its disappearance at the blue sky catastrophe.Comment: 4 pages, 6 figures, REVTeX, To be published in Physical Review Letter

Identity and Positive Youth Development: Advances in Developmental Intervention Science

This chapter provides an overview of advances in developmental intervention science that have contributed to an emerging literature on identity-focused positive youth development interventions. Rooted in the tradition of applied developmental science, developmental intervention science aims to advance the evolution of sustainable developmental intervention strategies targeting positive developmental outcomes. These developmental intervention strategies are intended to complement the wide array of well-established treatment and prevention intervention strategies targeting risky and problem behaviors. Within this framework, positive identity interventions seek to create empowering intervention contexts that promote the development of an increasingly integrated—and therefore an increasingly complex, coherent, and cohesive—self-constructed self-structure. By linking applied developmental science with treatment and prevention intervention science, developmental intervention science appears to have significant potential for facilitating the evolution of evidence-based positive development strategies for promoting positive life course change

Iron metabolism and lymphocyte characterisation during Covid-19 infection in ICU patients: An observational cohort study

Background: Iron metabolism and immune response to SARS-CoV-2 have not been described yet in intensive care patients, although they are likely involved in Covid-19 pathogenesis. Methods: We performed an observational study during the peak of pandemic in our intensive care unit, dosing D-dimer, C-reactive protein, troponin T, lactate dehydrogenase, ferritin, serum iron, transferrin, transferrin saturation, transferrin soluble receptor, lymphocyte count and NK, CD3, CD4, CD8 and B subgroups of 31 patients during the first 2 weeks of their ICU stay. Correlation with mortality and severity at the time of admission was tested with the Spearman coefficient and Mann-Whitney test. Trends over time were tested with the Kruskal-Wallis analysis. Results: Lymphopenia is severe and constant, with a nadir on day 2 of ICU stay (median 0.555 109/L; interquartile range (IQR) 0.450 109/L); all lymphocytic subgroups are dramatically reduced in critically ill patients, while CD4/CD8 ratio remains normal. Neither ferritin nor lymphocyte count follows significant trends in ICU patients. Transferrin saturation is extremely reduced at ICU admission (median 9%; IQR 7%), then significantly increases at days 3 to 6 (median 33%, IQR 26.5%, p value 0.026). The same trend is observed with serum iron levels (median 25.5 μg/L, IQR 69 μg/L at admission; median 73 μg/L, IQR 56 μg/L on days 3 to 6) without reaching statistical significance. Hyperferritinemia is constant during intensive care stay: however, its dosage might be helpful in individuating patients developing haemophagocytic lymphohistiocytosis. D-dimer is elevated and progressively increases from admission (median 1319 μg/L; IQR 1285 μg/L) to days 3 to 6 (median 6820 μg/L; IQR 6619 μg/L), despite not reaching significant results. We describe trends of all the abovementioned parameters during ICU stay. Conclusions: The description of iron metabolism and lymphocyte count in Covid-19 patients admitted to the intensive care unit provided with this paper might allow a wider understanding of SARS-CoV-2 pathophysiology

Partial Transmutation of Singularities in Optical Instruments

Some interesting optical instruments such as the Eaton lens and the Invisible Sphere require singularities of the refractive index for their implementation. We show how to transmute those singularities into harmless topological defects in anisotropic media without the need for anomalous material properties

Effectiveness of Fingolimod versus Natalizumab as Second-Line Therapy for Relapsing-Remitting Multiple Sclerosis in Spain: Second-Line GATE Study

Background: There is a lack of head-to-head studies comparing the efficacy of fingolimod (FIN) and natalizumab (NTZ) as second-line therapy for relapsing-remitting multiple sclerosis (RRMS). Methods: Multicenter, observational study, in which, information of 388 patients randomly selected and treated with FIN or NTZ in routine clinical practice was retrospectively collected with the main objective of comparing the annualized relapse rate (ARR) over the first year, after FIN or NTZ treatment initiation. Results: Mean ARR during the first year of treatment was 0.28 in FIN group and 0.12 in NTZ group (p = 0.0064); nevertheless, the difference between groups lost statistical significance when the propensity score analysis was performed. Time to disability -progression was similar in both treatment groups (12.3 +/- 6.7 months in FIN, and 12.8 +/- 0.1 months in NTZ; p = 0.4654). Treatment persistence after the first year of treatment was higher in patients treated with FIN (95%) than in those treated with NTZ (84%; p = 0.0014). Conclusions: After 12 months of treatment, both FIN and NTZ reduced the ARR, but ARR percent reduction was significantly higher with NTZ. Treatment persistence was higher in patients receiving FIN

Four-year safety and effectiveness data from patients with multiple sclerosis treated with fingolimod: The Spanish GILENYA registry

Esclerosis múltiple; Reacciones adversas; Infecciones respiratoriasEsclerosi múltiple; Reaccions adverses; Infeccions respiratòriesMultiple sclerosis; Adverse reactions; Respiratory infectionsObjective To describe the profile of patients with multiple sclerosis (MS) treated with fingolimod in Spain and to assess the effectiveness and safety of fingolimod after 4 years of inclusion in the Spanish Gilenya Registry. Methods An observational, retrospective/prospective, multicenter case registry, including all patients with relapsing-remitting MS (RRMS) starting treatment with fingolimod in 43 centers in Spain. Analyses were performed in the overall population and in subgroups according to prior disease-modifying therapy (DMT): glatiramer acetate/interferon beta-1 (BRACE), natalizumab, other treatment, or naïve. Results Six hundred and sixty-six evaluable patients were included (91.1% previously treated with at least one DMT). The mean annualized relapse rate (ARR) prior to fingolimod was 1.12, and the mean EDSS at fingolimod initiation was 3.03. Fingolimod reduced the ARR by 71.4%, 75%, 75.5%, and 80.3%, after 1, 2, 3 and 4 years, respectively (p<0.001). This significant reduction in the ARR continued to be observed in all subgroups. After 4 years, the EDSS showed a minimal deterioration, with the EDSS scores from year 1 to year 4 remaining mostly stable. The percentage of patients without T1 Gd+ lesions progressively increased from 45.6% during the year prior to fingolimod initiation to 88.2% at year 4. The proportion of patients free from new/enlarged T2 lesions after 4 years of fingolimod treatment was 80.3%. This trend in both radiological measures was also observed in the subgroups. Adverse events (AEs) were experienced by up to 41.6% of patients (most commonly: lymphopenia [12.5%] and urinary tract infection [3.7%]). Most AEs were mild in severity, 3.6% of patients had serious AEs. Conclusions The patient profile was similar to other observational studies. The results obtained from the long-term use of fingolimod showed that it was effective, regardless of prior DMT, and it had adequate safety results, with a positive benefit-risk balance.The study was funded by the Academia Española de Esclerosis Múltiple y Otras Enfermedades Autoinmunes (ACADEM), with a restricted investigational grant form Novartis. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Four-year safety and effectiveness data from patients with multiple sclerosis treated with fingolimod : The Spanish GILENYA registry

Objective To describe the profile of patients with multiple sclerosis (MS) treated with fingolimod in Spain and to assess the effectiveness and safety of fingolimod after 4 years of inclusion in the Spanish Gilenya Registry. Methods An observational, retrospective/prospective, multicenter case registry, including all patients with relapsing-remitting MS (RRMS) starting treatment with fingolimod in 43 centers in Spain. Analyses were performed in the overall population and in subgroups according to prior disease-modifying therapy (DMT): glatiramer acetate/interferon beta-1 (BRACE), natalizumab, other treatment, or naïve. Results Six hundred and sixty-six evaluable patients were included (91.1% previously treated with at least one DMT). The mean annualized relapse rate (ARR) prior to fingolimod was 1.12, and the mean EDSS at fingolimod initiation was 3.03. Fingolimod reduced the ARR by 71.4%, 75%, 75.5%, and 80.3%, after 1, 2, 3 and 4 years, respectively (p<0.001). This significant reduction in the ARR continuedto be observed in all subgroups. After 4 years, the EDSS showed a minimal deterioration, with the EDSS scores from year 1 to year 4 remaining mostly stable. The percentage of patients without T1 Gd+ lesions progressively increased from 45.6% during the year prior to fingolimod initiation to 88.2% at year 4. The proportion of patients free from new/enlarged T2 lesions after 4 years of fingolimod treatment was 80.3%. This trend in both radiological measures was also observed in the subgroups. Adverse events (AEs) were experienced by up to 41.6% of patients (most commonly: lymphopenia [12.5%] and urinary tract infection [3.7%]). Most AEs were mild in severity, 3.6% of patients had serious AEs. Conclusions The patient profile was similar to other observational studies. The results obtained from the long-term use of fingolimod showed that it was effective, regardless of prior DMT, and it had adequate safety results, with a positive benefit-risk balance

Temperature-treated gluten proteins in Gluten-Friendly™ bread increase mucus production and gut-barrier function in human intestinal goblet cells

Abstract The effects of a control bread (CB) and a Gluten Friendly™ bread (GFB) on intestinal epithelium mucus production and barrier function in healthy human mucus-secreting goblet cells HT-29-16E were investigated. Mucus production in cells exposed to digested breads (GFB and CB) was preliminarily investigated using staining techniques, Periodic Acid-Schiff (PAS) and Alcian blue (AB), and MUC2 and MUC3 were also quantified by ELISA assay. The barrier function of the cell monolayer was evaluated by trans-epithelial electrical resistance (TEER) measurements. GFB increased the secretion of mucins, expressed as the level of PAS and AB staining in comparison with the control. MUC3 levels were not affected, whereas higher MUC2 concentrations (

Detecting new physics contributions to the D0-D0bar mixing through their effects on B decays

New physics effects may yield a detectable mass difference in the D0-D0bar system, Delta m_D. Here we show that this has an important impact on some B --> D decays. The effect involves a new source of CP violation, which arises from the interference between the phases in the B --> D decays and those in the D0-D0bar system. This interference is naturally large. New physics may well manifest itself through Delta m_D contributions to these B decays.Comment: 10 pages, Revtex, no figures. To appear in PR

Impact of D0-D0bar mixing on the experimental determination of gamma

Several methods have been devised to measure the weak phase gamma using decays of the type B+- --> D K+-, where it is assumed that there is no mixing in the D0-D0bar system. However, when using these methods to uncover new physics, one must entertain the real possibility that the measurements are affected by new physics effects in the D0-D0bar system. We show that even values of x_D and/or y_D around 10^{-2} can have a significant impact in the measurement of sin^2{gamma}. We discuss the errors incurred in neglecting this effect, how the effect can be checked, and how to include it in the analysis.Comment: 18 pages, Latex with epsfig, 8 figure