Characterization of Serial Links at 5.5Gbps on FR4 Backplanes

Nowdays the fast and increased demand for bandwidth in the telecommunication world translates into the design of complex boards exchanging data at high bit rate in reduced design cycle. Sometimes it is impossible to spent time in setting pre-layout simulations, because they are not compatible with the design time schedule. In this scenario it is better to design the boards using experience and then make simulations in conjunction with measurements, using customized numerical tools which don\u27t need complex models

Novel Therapeutic Approaches in Rheumatoid Arthritis: Role of Janus Kinases Inhibitors.

Rheumatoid Arthritis (RA) is a chronic inflammatory disease characterized by synovial inflammation and hyperplasia, autoantibody production, cartilage and bone destruction and several systemic features. Cardiovascular, pulmonary, psychological, and muscle involvement are the main comorbidities of RA and are responsible for the severity of the disease and long-term prognosis. Pharmacological treatment of rheumatic diseases has evolved remarkably over the past years. In addition, the widespread adoption of treat to target and tight control strategies has led to a substantial improvement of outcomes, so that drug-free remission is nowadays a realistic goal in the treatment of RA. However, despite the availability of multiple therapeutic options, up to 40% of patients do not respond to current treatments, including biologics. Small-molecule therapies offer an alternative to biological therapies for the treatment of inflammatory diseases. In the past 5 years, a number of small-molecule compounds targeting Janus Kinases (JAKs) have been developed. Since JAKs are essential for cell signaling in immune cells, in particular controlling the response to many cytokines, their inhibitors quickly became a promising class of oral therapeutics that proved effective in the treatment of RA. Tofacitinib is the first Janus Kinase (JAK) inhibitor approved for the treatment of RA, followed more recently by baricitinib. Several other JAK inhibitors, are currently being tested in phase II and III trials for the treatment of a different autoimmune diseases. Most of these compounds exhibit an overall acceptable safety profile similar to that of biologic agents, with infections being the most frequent adverse event. Apart from tofacitinib, safety data on other JAK inhibitors are still limited. Long-term follow-up and further research are needed to evaluate the general safety profile and the global risk of malignancy of these small molecules, although no clear association with malignancy has been reported to date. Here, we will review the main characteristics of JAK inhibitors, including details on their molecular targets and on the clinical evidences obtained so far in the treatment of RA

Aggiornamento tecnologico e test funzionali del gravimetro da fondo LaCoste&Romberg modello U-HG24

Nel presente lavoro viene descritto l’aggiornamento tecnologico, effettuato in collaborazione con la società Tecnomare SpA, di un gravimetro da fondo LaCoste & Romberg modello U, serie H (numero HG24), di proprietà dell'Istituto Nazionale di Geofisica e Vulcanologia. Sono inoltre descritti e brevemente discussi i primi test in laboratorio ed i risultati di misure gravimetriche di fondo mare effettuate dal 19 al 22 Luglio 2010 nell'Area Marina Protetta del Parco Nazionale delle Cinque Terre. L'acquisizione di dati gravimetrici rientrava nelle attività specifiche del progetto di ricerca InSAS promosso e finanziato da eni Spa. La campagna a mare InSAS si è svolta in collaborazione con il NURC (NATO Undersea Research Centre) utilizzando come vettore marino il Coastal Research Vessel (CRV) ‘Leonardo’. Contestualmente all'attività di misure di gravità di fondo, sono stati acquisiti ed elaborati dal Politecnico di Milano diversi set di dati interferometrici Synthetic Aperture Sonar (SAS) su alcuni riflettori attivi e passivi localizzati nell'area di indagine. La campagna di misure a mare è stata preceduta da una serie di test in laboratorio al fine di valutare la piena funzionalità dello strumento in esame. In questa fase sono state acquisite diverse serie temporali allo scopo di valutare la qualità della misura e la sua ripetibilità

Buccal mucosa is a promising graft in Peyronie's disease surgery. Our experience and a brief literature review on autologous grafting materials

AIM: Peyronie's Disease (PD) is an under reported acquired benign condition that, at the moment, is not curable with medical therapy. Surgery represent the gold standard of treatment. Surgical approaches are several and they consist in "plication techniques" or plaque incision/excision with grafting of resulting albuginea defect. Among grafting procedures, albuginea defect substitution with autologous materials demonstrated over the years not inferior results respect to heterologous grafts. Buccal mucosa graft (BMG) is not usually emphasized in many review articles and clinical series are yet limited. METHODS: We present our experience with seventeen plaque incision procedures and BMG in surgical correction of complex penile curvatures due to PD performed in a period of 30 months. Our analyses was focused on buccal mucosa graft characteristics as major determinant of the surgical success. We also conducted a brief literature review on autologous grafting materials used in reconstructive penile surgery for PD. RESULTS: Our cosmetics and functional results consists in a 100% of functional penile straightening with no relapses and 5,8% of de novo erectile dysfunction. Mean age was 56.4 years, mean follow-up of 22.5 (6-36) months. No complications graft related were observed. Operative time was 115.3 minutes in mean. Over 94% of patients referred they were "really much better" and "much better" satisfied based on PGI-I questionnaire administrated at the last follow- up visit. CONCLUSION: BMG is revealing as an optimal choice for reconstructive surgery in PD. Anatomical characteristics consisting in the great elasticity, the quick integration time and the easy harvesting technique lead to high cosmetics and functional success rate, without omitting economical and invasiveness aspects

Suppression of β1-adrenoceptor autoantibodies is involved in the antiarrhythmic effects of omega-3 fatty acids in male and female hypertensive rats

The arrhythmogenic potential of β1-adrenoceptor autoantibodies (β1-AA), as well as antiarrhythmic properties of omega-3 in heart diseases, have been reported while underlying mechanisms are poorly understood. We aimed to test our hypothesis that omega-3 (eicosapentaenoic acid-EPA, docosahexaenoic acid-DHA) may inhibit matrix metalloproteinase (MMP-2) activity to prevent cleavage of β1-AR and formation of β1-AA resulting in attenuation of pro-arrhythmic connexin-43 (Cx43) and protein kinase C (PKC) signaling in the diseased heart. We have demonstrated that the appearance and increase of β1-AA in blood serum of male and female 12-month-old spontaneously hypertensive rats (SHR) was associated with an increase of inducible ventricular fibrillation (VF) comparing to normotensive controls. In contrast, supplementation of hypertensive rats with omega-3 for two months suppressed β1-AA levels and reduced incidence of VF. Suppression of β1-AA was accompanied by a decrease of elevated myocardial MMP-2 activity, preservation of cardiac cell membrane integrity and Cx43 topology. Moreover, omega-3 abrogated decline in expression of total Cx43 as well as its phosphorylated forms at serine 368 along with PKC-ε, while decreased pro-fibrotic PKC-δ levels in hypertensive rat heart regardless the sex. The implication of MMP-2 in the action of omega-3 was also demonstrated in cultured cardiomyocytes in which desensitization of β1-AR due to permanent activation of β1-AR with isoproterenol was prevented by MMP-2 inhibitor or EPA. Collectively, these data support the notion that omega-3 via suppression of β1-AA mechanistically controlled by MMP-2 may attenuate abnormal of Cx43 and PKC signaling; thus, abolish arrhythmia substrate and protect rats with an advanced stage of hypertension from malignant arrhythmias

Immunosuppressive therapy with rituximab in common variable immunodeficiency.

Common variable immunodeficiency (CVID) is the most frequent symptomatic primary antibody deficiency in adulthood and is characterized by the marked reduction of IgG and IgA serum levels. Thanks to the successful use of polyvalent immunoglobulin replacement therapy to treat and prevent recurrent infections, non-infectious complications, including autoimmunity, polyclonal lymphoproliferation and malignancies, have progressively become the major cause of morbidity and mortality in CVID patients. The management of these complications is particularly challenging, often requiring multiple lines of immunosuppressive treatments. Over the last 5-10 years, the anti-CD20 monoclonal antibody (i.e., rituximab) has been increasingly used for the treatment of both autoimmune and non-malignant lymphoproliferative manifestations associated with CVID. This review illustrates the evidence on the use of rituximab in CVID. For this purpose, first we discuss the mechanisms proposed for the rituximab mediated B-cell depletion; then, we analyze the literature data regarding the CVID-related complications for which rituximab has been used, focusing on autoimmune cytopenias, granulomatous lymphocytic interstitial lung disease (GLILD) and non-malignant lymphoproliferative syndromes. The cumulative data suggest that in the vast majority of the studies, rituximab has proven to be an effective and relatively safe therapeutic option. However, there are currently no data on the long-term efficacy and side effects of rituximab and other second-line therapeutic options. Further randomized controlled trials are needed to optimize the management strategies of non-infectious complications of CVID

The immune landscape of thyroid cancer in the context of immune checkpoint inhibition

Immune cells play critical roles in tumor prevention as well as initiation and progression. However, immune-resistant cancer cells can evade the immune system and proceed to form tumors. The normal microenvironment (immune cells, fibroblasts, blood and lymphatic vessels, and interstitial extracellular matrix (ECM)) maintains tissue homeostasis and prevents tumor initiation. Inflammatory mediators, reactive oxygen species, cytokines, and chemokines from an altered microenvironment promote tumor growth. During the last decade, thyroid cancer, the most frequent cancer of the endocrine system, has emerged as the fifth most incident cancer in the United States (USA), and its incidence is steadily growing. Inflammation has long been associated with thyroid cancer, raising critical questions about the role of immune cells in its pathogenesis. A plethora of immune cells and their mediators are present in the thyroid cancer ecosystem. Monoclonal antibodies (mAbs) targeting immune checkpoints, such as mAbs anti-cytotoxic T lymphocyte antigen 4 (anti-CTLA-4) and anti-programmed cell death protein-1/programmed cell death ligand-1 (anti-PD-1/PD-L1), have revolutionized the treatment of many malignancies, but they induce thyroid dysfunction in up to 10% of patients, presumably by enhancing autoimmunity. Combination strategies involving immune checkpoint inhibitors (ICIs) with tyrosine kinase (TK) or serine/threonine protein kinase B-raf (BRAF) inhibitors are showing considerable promise in the treatment of advanced thyroid cancer. This review illustrates how different immune cells contribute to thyroid cancer development and the rationale for the antitumor effects of ICIs in combination with BRAF/TK inhibitors

System Level PDN Impedance Optimization Utilizing the Zeros of the Decoupling Capacitors

System-Level Power Distribution Network (PDN) Impedance Optimization Utilizing the Zeros of the Decoupling Capacitors (Decaps) is Discussed in This Paper. an Example of a Practical PDN Application is Proposed to Validate the Poles and Zeros Algorithm (P&Z) Presented. the System-Level PDN is with the Printed Circuit Board (PCB), Package (PKG), and Chip, as Well as the Low-Frequency Decaps on the PCB and the On-PKG Decoupling Capacitors. the PDN Optimization Results Are Compared with Those from the Genetic Algorithm (GA) to Show the Reasonableness and Validity of the P&Z Algorithm

The effect of bilateral internal thoracic artery harvesting on superficial and deep sternal infection: The role of skeletonization

Objective: To determine the relative risk of sternal dehiscence in patients undergoing bilateral internal thoracic artery harvesting and to assess whether and to what extent the technique of artery skeletonization might reduce this risk. Methods: Prospectively collected data on patients undergoing coronary artery bypass operations with at least a single internal thoracic artery were reviewed. The last 450 patients receiving bilateral internal thoracic artery grafts were compared with 450 patients who received a single internal thoracic artery during the same period. The left internal thoracic artery was always harvested in a pedicled fashion. Among patients receiving a bilateral internal thoracic artery, both arteries were harvested in a pedicled fashion in 300 cases, whereas both internal thoracic arteries were skeletonized in the remaining 150 cases. Results: Compared with a single internal thoracic artery, harvesting both internal thoracic arteries either in a skeletonized or in a pedicled fashion increased the chance of deep (1.1% vs 3.3% vs 4.7%; P =. 01) or superficial (4.8% vs 7.8% vs 12%; P =. 002) sternal infection. However, the technique of artery harvesting (odds ratio, 4.1; 95% confidence interval, 1.4-12.1); the presence of peripheral arteriopathy (odds ratio, 3.1; 95% confidence interval, 1.2-8.5), and resternotomy for bleeding (odds ratio, 8.2; 95% confidence interval, 2.0-33.6) were the only independent predictors for deep sternal infection, whereas the technique of artery harvesting (odds ratio, 3.0; 95% confidence interval, 1.6-5.4), female sex (odds ratio, 2.2; 95% confidence interval, 1.2-4.2), and diabetes (odds ratio, 1.7; 95% confidence interval, 1.0-2.9) were the only independent predictors of superficial sternal infection. In diabetic patients, there was no difference in the incidence of deep sternal infection among patients receiving a single internal thoracic artery or double skeletonized internal thoracic arteries (P =. 4). Conclusions: Bilateral internal thoracic artery harvesting carries a higher risk of sternal infection than harvesting a single internal thoracic artery. Skeletonization of both internal thoracic arteries significantly decreases this risk. A strategy of bilateral thoracic artery grafting can also be offered to patients at high risk for wound infection. Copyright © 2005 by The American Association for Thoracic Surgery