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Sample records for persisting mixed cryoglobulinemia

  1. Mixed cryoglobulinemia

    PubMed Central

    Ferri, Clodoveo

    2008-01-01

    Mixed cryoglobulinemia (MC), type II and type III, refers to the presence of circulating cryoprecipitable immune complexes in the serum and manifests clinically by a classical triad of purpura, weakness and arthralgias. It is considered to be a rare disorder, but its true prevalence remains unknown. The disease is more common in Southern Europe than in Northern Europe or Northern America. The prevalence of 'essential' MC is reported as approximately 1:100,000 (with a female-to-male ratio 3:1), but this term is now used to refer to a minority of MC patients only. MC is characterized by variable organ involvement including skin lesions (orthostatic purpura, ulcers), chronic hepatitis, membranoproliferative glomerulonephritis, peripheral neuropathy, diffuse vasculitis, and, less frequently, interstitial lung involvement and endocrine disorders. Some patients may develop lymphatic and hepatic malignancies, usually as a late complication. MC may be associated with numerous infectious or immunological diseases. When isolated, MC may represent a distinct disease, the so-called 'essential' MC. The etiopathogenesis of MC is not completely understood. Hepatitis C virus (HCV) infection is suggested to play a causative role, with the contribution of genetic and/or environmental factors. Moreover, MC may be associated with other infectious agents or immunological disorders, such as human immunodeficiency virus (HIV) infection or primary Sjögren's syndrome. Diagnosis is based on clinical and laboratory findings. Circulating mixed cryoglobulins, low C4 levels and orthostatic skin purpura are the hallmarks of the disease. Leukocytoclastic vasculitis involving medium- and, more often, small-sized blood vessels is the typical pathological finding, easily detectable by means of skin biopsy of recent vasculitic lesions. Differential diagnoses include a wide range of systemic, infectious and neoplastic disorders, mainly autoimmune hepatitis, Sjögren's syndrome, polyarthritis, and B

  2. Mixed cryoglobulinemia.

    PubMed

    Ferri, Clodoveo

    2008-09-16

    Mixed cryoglobulinemia (MC), type II and type III, refers to the presence of circulating cryoprecipitable immune complexes in the serum and manifests clinically by a classical triad of purpura, weakness and arthralgias. It is considered to be a rare disorder, but its true prevalence remains unknown. The disease is more common in Southern Europe than in Northern Europe or Northern America. The prevalence of 'essential' MC is reported as approximately 1:100,000 (with a female-to-male ratio 3:1), but this term is now used to refer to a minority of MC patients only. MC is characterized by variable organ involvement including skin lesions (orthostatic purpura, ulcers), chronic hepatitis, membranoproliferative glomerulonephritis, peripheral neuropathy, diffuse vasculitis, and, less frequently, interstitial lung involvement and endocrine disorders. Some patients may develop lymphatic and hepatic malignancies, usually as a late complication. MC may be associated with numerous infectious or immunological diseases. When isolated, MC may represent a distinct disease, the so-called 'essential' MC. The etiopathogenesis of MC is not completely understood. Hepatitis C virus (HCV) infection is suggested to play a causative role, with the contribution of genetic and/or environmental factors. Moreover, MC may be associated with other infectious agents or immunological disorders, such as human immunodeficiency virus (HIV) infection or primary Sjögren's syndrome. Diagnosis is based on clinical and laboratory findings. Circulating mixed cryoglobulins, low C4 levels and orthostatic skin purpura are the hallmarks of the disease. Leukocytoclastic vasculitis involving medium- and, more often, small-sized blood vessels is the typical pathological finding, easily detectable by means of skin biopsy of recent vasculitic lesions. Differential diagnoses include a wide range of systemic, infectious and neoplastic disorders, mainly autoimmune hepatitis, Sjögren's syndrome, polyarthritis, and B

  3. Mixed cryoglobulinemia: new concepts.

    PubMed

    Ramos-Casals, M; Trejo, O; García-Carrasco, M; Cervera, R; Font, J

    2000-01-01

    The most documented extrahepatic manifestation of hepatitis C virus (HCV) infection is mixed cryoglobulinemia (MC). MC is characterised by the presence of temperature-sensitive protein complexes: in type II MC, cryoglobulins are composed of a monoclonal rheumatoid factor (usually, IgMkappa) against polyclonal IgG. In type III MC, all components are polyclonal. The presence of microheterogeneity and other new types of cryoglobulins is a novel and recent observation. The production of different autoantibodies and circulating immune complexes, including the cryoglobulins, are responsible for systemic vasculitis and various organ damage. In a limited number of MC patients, a malignancy, that is B-cell non-Hodgkin's lymphoma or hepatocellular carcinoma, may also develop. Finally, results of interferon and/or ribavirin treatments in MC patients represent an indirect proof for the pathogenetic link between MC and HVC infection. The discovery of the relation between HCV infection and MC shows the striking association between a viral infection and an autoimmune disease and, thus, a potential link between the systemic autoimmune and lymphoproliferative disorders.

  4. [Cryoglobulinemia].

    PubMed

    Ottl, Tobias; Trendelenburg, Marten

    2008-05-01

    Cryoglobulins are immunoglobulins that precipitate at temperatures below 37 degrees C. They mainly occur in association with hepatitis C but also in other persistent viral infections and autoimmune as well as hematologic diseases. As circulating immune-complexes, they can cause severe tissue damage in virtually all organs, in particular the skin, joints and kidneys. This article gives a review on the different types of cryoglobulinemia, their clinical presentation and current therapeutic strategies.

  5. Hepatitis C Virus Infection and Mixed Cryoglobulinemia

    PubMed Central

    Lauletta, Gianfranco; Russi, Sabino; Conteduca, Vincenza; Sansonno, Loredana

    2012-01-01

    Hepatitis C virus (HCV) chronic infection is recognized as the major cause of mixed cryoglobulinemia (MC). Its persistence represents a continuous stimulus for host immune system with production of circulating immune complexes (ICs), one-third of them with cryoprecipitate property. Several factors contribute to the biological activities of ICs, many of which are not completely known. Among them, complement factors play a crucial role in the cold-insoluble ICs-mediated vasculitis, involving primarily small blood vessels in different tissues including skin, kidney, peripheral, and central nervous system. Liver represents the major target of HCV infection with inflammatory infiltrates, resembling secondary lymphoid follicles. Cytokine like CXCL13 contribute to B-cell homing in intraportal lymphoid aggregates, in which B-cell clonal selection may arise. B-cell clonal expansion starts as an antigen-driven event and expands towards indolent and malignant B-cell proliferation. Occurrence of intrahepatic B-cell clonalities correlates with extrahepatic clinical manifestations of HCV infection. In this context, cryoglobulinemic patients should be considered a peculiar HCV-infected population that needs a clinical multidisciplinary approach and more articulated therapeutic measures. PMID:22844322

  6. Persistence of mixed cryoglobulinemia despite cure of hepatitis C with new oral antiviral therapy including direct-acting antiviral sofosbuvir: A case series.

    PubMed

    Cornella, Scott L; Stine, Jonathan G; Kelly, Virginia; Caldwell, Stephen H; Shah, Neeral L

    2015-05-01

    Obtaining a sustained virologic response (SVR) in patients with chronic hepatitis C virus (HCV) can decrease hepatic complications and be curative, however, extrahepatic manifestations including mixed cryoglobulinemia (MCN) may persist with interferon-based therapy. Our objective was to review our experience in treating patients with new oral antiviral agents and to assess common factors associated with MCN persistence despite SVR. We analyzed a case series of five patients with genotype one chronic HCV complicated by MCN who had persistence of cryoglobulins despite completion of triple therapy with oral antiviral agents (boceprivir, telaprivir or sofosbuvir). Patients with cirrhosis appear to have a decreased ability to clear immune complexes. We observed that early viral response by week 8 of therapy and longer periods of undetectable virus on treatment correlated with eventual clearance of serum cryoglobulins in patients without cirrhosis. Two patients were treated with anti-B-cell agent rituximab prior to starting therapy for HCV; this did not lead to a more effective clearance of cryoglobulins. We suggest that a longer treatment course than the standard 24 weeks with triple therapy could aid in the clearance of these immune complexes and cryoglobulins in cirrhotics. More studies to determine the ideal duration of treatment for chronic HCV and coincident MCN are needed, especially in light of the new all oral direct-acting antiviral regimens that are now recommended for HCV treatment.

  7. Cryoglobulinemia.

    PubMed

    Tedeschi, Alessandra; Baratè, Claudia; Minola, Ernesto; Morra, Enrica

    2007-07-01

    Cryoglobulinemia refers to the presence in serum of immunoglobulins that precipitate at a cold temperature. Type I cryoglobulins are single monoclonal immunoglobulins usually associated with haematological disorders. Types II and III are mixed cryoglobulins, composed of monoclonal or polyclonal IgM respectively, having rheumatoid factor activity that bind to polyclonal immunoglobulins. Mixed cryoglobulinemia (MC) syndrome is a consequence of immune-complex mediated vasculitis and is characterized by a typical clinical triad: purpura, weakness, arthralgias; many organs particularly kidney and peripheral nervous system may be involved. MC may be associated with infectious and systemic disorders and since 1990 studies have demonstrated that hepatitis C virus (HCV) may be considered the principal trigger of the disease. The relation between MC and HCV infection shows new insights in the interpretation of the link between viral infection, autoimmune phenomena and lymphoproliferative disorders evolution. In fact, the virus chronically stimulates B-cell polyclonal proliferation from which a monoclonal population may emerge. In symptomatic patients with HCV related MC therapeutic strategy should include an attempt at viral eradication. Antiviral therapy may also be effective in determining the regression of B-cell lymphoproliferative disorder. Rituximab could represent a safe and effective alternative to standard immunosuppression and exerts selective B-cell control.

  8. Mixed cryoglobulinemia and thyroid autoimmune disorders.

    PubMed

    Fallahi, P; Ferrari, S M; Giuggioli, D; Corrado, A; Fabiani, S; Marchi, S; Ferri, C; Antonelli, A

    2013-01-01

    In patients with hepatitis C virus-associated mixed cryoglobulinemia (MC+HCV) the following thyroid disorders are significantly more frequent than in HCV not infected controls: 1) high levels of serum anti-thyroperoxidase autoantibody (AbTPO), 2) high levels of serum AbTPO and/or anti-thyroglobulin (AbTg) autoantibody; 3) humoral and ultrasonographical signs of thyroid autoimmunity (35%); 4) prevalence of subclinical hypothyroidism (11%). Also, the prevalence of papillary thyroid cancer has been found higher in MC+HCV patients than in controls, in particular in patients with autoimmune thyroiditis. These results suggest a careful monitoring of thyroid function in these patients.

  9. B-cells and mixed cryoglobulinemia.

    PubMed

    Ferri, Clodoveo; Antonelli, Alessandro; Mascia, Maria Teresa; Sebastiani, Marco; Fallahi, Poupak; Ferrari, Daniela; Giunti, Marco; Pileri, Stefano A; Zignego, Anna Linda

    2007-12-01

    Mixed cryoglobulinemia (MC) is a systemic small-vessel vasculitis; B-cell expansion is the biological substrate of the disease. It can be regarded as benign lymphoproliferative condition that may evolve to frank lymphoma. HCV infection is the main causative factor of MC, as well as of other overlapping disorders, through multifactorial and multistep pathogenetic process. HCV-related B-cell proliferation represents an important model of virus-driven autoimmune/neoplastic disorder. The term HCV syndrome is referred to a wide spectrum of both hepatic and extrahepatic disorders. The present review analyzes the complex virological, clinico-pathological, and therapeutic implications of B-cell proliferation, with or without HCV infection, in MC patients.

  10. Non HCV-related mixed cryoglobulinemia.

    PubMed

    Mascia, M T; Ferrari, D; Campioli, D; Sandri, G; Mussini, C; Ferri, C

    2007-09-01

    A striking association (>90%) between mixed cryoglobulinemia (MC) and hepatitis C virus (HCV) infection has been established by means of clinico-epidemiological and laboratory studies. However, little information is available as regards the etiopathogenesis and the actual percentage of HCV-negative MC. This latter seems to be more frequent in the same geographical areas where the overall prevalence of MC is low. In 195 Italian patients with serum mixed cryoglobulins consecutively analyzed at the laboratory of our hospital, during one year, the prevalence of HCV-negative MC was 15.9%. Moreover, we evaluated the clinico-serological characteristics of our whole series of 65 HCV-negative MC patients: "essential" MC was present in only 25%, while the majority of cases showed different connective tissue diseases or neoplastic disorders. Interestingly, patients with Sjögren's syndrome or lymphoma had higher levels of cryocrit with cryoglobulinemic syndrome comparable to that found in HCV-positive MC patients. MC is a multifactorial disorder; considering possible etiological factors and clinical associations the disease may present different subsets: the prevalent group of HCV-positive MC; HCV-positive MC associated with different autoimmune lymphoproliferative disorders; two MC subsets without any apparent causative agent: those with well-known autoimmune lymphoproliferative disorders and the rare cases of "essential" MC; and finally MC associated with other infectious agents.

  11. Treatment of HCV-Related Mixed Cryoglobulinemia.

    PubMed

    Giuggioli, Dilia; Sebastiani, Marco; Colaci, Michele; Fallahi, Poupak; Gragnani, Laura; Zignego, Anna Linda; Antonelli, Alessandro; Ferri, Clodoveo

    2017-01-01

    Mixed cryoglobulinemia syndrome (MCs) is a systemic vasculitis, involving skin, joints, peripheral nerves, and several internal organs. Hepatitis C virus (HCV) is recognized as the etiologic agent for the majority of MCs patients, as well as of number of autoimmune, lymphoproliferative, and neoplastic disorders. In this context, HCV-related MCs represents an important model autoimmune/ neoplastic disease triggered by a virus in humans. With regard the therapeutic strategies of MCs, we can treat these patients at different steps by means of etiological (antivirals), pathogenetic, symptomatic drugs (mainly immunosuppressors, corticosteroids, plasmapheresis). In the majority of individuals, MCs shows a mild, slow-progressive clinical course needing only symptomatic treatments, generally low doses of corticosteroids. Considering the etiopathogenesis of MCs, the eradication of HCV should be considered the gold standard in the treatment of MCs. The use of combined peg-interferon- α/ribavirin and/or novel antiviral drugs may lead to HCV eradication in a significant percentage of cases with possible remission of MCs. On the other hand, the presence of rapidly progressive, diffuse vasculitis with multiple organ involvement may be successfully treated with aggressive immunosuppressive and anti-inflammatory therapies, mainly based on cyclophosphamide or rituximab, high dose corticosteroids, and plasma aphaeresis. Moreover, sequential/combined antiviral or immunosuppressive treatments could represent an useful therapeutic strategy particularly in MCs patients with major clinical manifestations. The treatment of MCs should be decided for every patient according to the severity of clinical picture. Thus, a careful follow-up of the disease is necessary, with particular attention to the possibility of cancers onset, such as B-cell lymphoma. The present review focuses on the different therapeutic strategies in patients with MCs, including the treatment of cryoglobulinemic skin

  12. [Cryoglobulinemia].

    PubMed

    Cacoub, P; Sène, D; Saadoun, D

    2008-03-01

    Cryoglobulinemia are immune complexes that may induce systemic cryoglobulinemic vasculitis. Cryoglobulin may be an isolated biological abnormality or may induce clinical manifestations of a systemic vasculitis, involving the skin, the joints, the peripheral nerve system and the kidneys. During the last 15 years, major advances have been obtained after the discovery of the hepatitis C virus, the main cause of cryoglobulins. Main factors associated with cryoglobulin production are female gender, alcohol intake above 50 g per day, extensive liver fibrosis and steatosis. Symptomatic cryoglobulins (i.e., vasculitis) are associated with older age, longer duration of infection and main characteristics of cryoglobulin itself (type II, IgM kappa, high serum levels). The pathophysiology is complex and involves humoral immunity, B and T cellular immunity, but not directly the virus itself. Peg-interferon-alpha and ribavirin combination leads to a virological and clinical response of the vasculitis in about 70% of patients. In non responders, recent open series suggested the efficacy of rituximab with a good response in up to 80% of patients, but a relapse in 42% seven months after the last infusion. New therapeutic strategies include a combination of best antiviral treatment with Peg-interferon-alpha plus ribavirin and rituximab. Multicenter controlled trials are mandatory.

  13. Splenectomy may improve the glomerulopathy of type II mixed cryoglobulinemia.

    PubMed

    Ubara, Y; Hara, S; Katori, H; Tagami, T; Kitamura, A; Yokota, M; Matsushita, Y; Takemoto, F; Yamada, A; Nagahama, K; Hara, M; Chayama, K

    2000-06-01

    Many patients with type II mixed cryoglobulinemia have been shown to be infected with hapatitis C virus (HCV). Therefore, interferon-alfa has become the first choice of treatment for patients with HCV-associated cryoglobulinemia. However, the disease often relapses after the discontinuation of interferon therapy. The long-term effect of interferon therapy is controversial. Therefore, a more effective therapy needs to be developed. A 62-year-old Japanese woman was admitted to our hospital for the examination of abnormal liver function tests, severe edema, and purpura in her lower extremities. Glomerulopathy secondary to HCV-related cryoglobulinemia was suspected. Her serum creatinine was increased to 2.1 mg/dL. Interferon therapy was considered initially. However, because of pancytopenia caused by liver cirrhosis and splenomegaly, splenectomy was performed in February 1997, before the start of interferon therapy. Renal biopsy specimen taken at the time of the splenectomy showed typical cryoglobulinemic glomerulonephritis. Gradually, after surgery, the patient's thrombocytopenia and anemia improved, her proteinuria and hematuria were decreased, her cryocrit dropped from 15% to 5%, the Ccr increased from 21.1 mL/min to 48.8 mL/min, and the purpura in her lower extremities disappeared. A repeat renal biopsy performed in May 1998 showed marked histological improvement. Splenectomy is not widely accepted as a treatment for cryoglobulinemia. Our case suggests the possibility that the monoclonal-IgM component of the type II cryoglobulin may be formed in the spleen. In conclusion, splenectomy may be an effective therapy for cryoglobulinemia in patients with HCV-positive liver cirrhosis and pancytopenia secondary to splenomegaly.

  14. Antiviral therapy of symptomatic HCV-mixed cryoglobulinemia after liver transplant: case report and literature review.

    PubMed

    Francesca Donato, Maria; Banfi, Giovanni; Cresseri, Donata; Battista Fogazzi, G; Martin, Paul; Messa, Piergiorgio; Fabrizi, Fabrizio

    2013-05-17

    Hepatitis C virus (HCV) infection may be associated with extra-hepatic illness including mixed cryoglobulinemia (MC). Consistent evidence exists on HCV-MC in the non-transplantation setting but information on HCV-related cryoglobulinemia after solid organ transplantation is limited, particularly after liver transplantation (LT). We report on a 48-year-old man who developed HCV-associated cryoglobulinemic vasculitis with recurrent hepatitis after liver transplant. One year after transplant for HCV-positive 
cirrhosis, he presented severe cutaneous manifestations, and biopsy-proven cryoglobulinemic membrano-proliferative glomerulonephritis (MPGN). HCV RNA clearance occurred within a few weeks of antiviral therapy; sustained viral response (SVR) was obtained by one year of anti-HCV combination therapy (eight months of pegylated IFN/ribavirin and four months of standard IFN/ribavirin). SVR was linked to complete remission of skin, liver, and kidney abnormalities. Tolerance to the pegylated IFN/ribavirin regimen was not excellent due to the occurrence of lobar pneumonia with anemia; thus, peg-IFN was replaced by recombinant IFN, with a favorable outcome. Clinical and viral remission persisted over a 48-month follow-up. HCV-associated mixed cryoglobulinemia flareups following LT were successfully managed with combined antiviral therapy. HCV-related MC is uncommon in developed countries and this clearly hampers randomized controlled clinical trials aimed at evaluating the efficacy and safety of anti-HCV therapy after solid organ transplantation or in the non-transplantation setting.

  15. [Cryoglobulinemia in chronic hepatitis C virus infection. About 76 cases].

    PubMed

    Monia, Fekih; Lamia, Bouallegue; Jalel, Boubaker; Samira, Matri; Amel, Sassi; Azza, Filali

    2005-11-01

    Cryolobulines are immunoglobulins that persist in the serum, precipitate with cold temperature and resolubilize when rewarmed. There are 3 types of cryoglobulinemia. Type II and III define mixed cryoglobulinemia. 40% approximately of patients with chronic hepatitis C virus (HCV) infection had cryoglobulinemia. To evaluate the frequency of cryoglobulinemia in a chronic hepatitis virus (CHV) infection group and determine the characteristics of positive cryoglobulinemia patients. 76 patients were included. There were 53 women an 23 men. The mean age was 59.45 years. Mixed cryoglobulinemia was detected in 65 patients (85.5 %). Cirrhosis, old age and the long duration of CHV infection were the 3 factors associated with cryoglobulinemia positivity. Mixed cryoglobulinemia is a frequent manifestation during chronic hepatitis C infection virsus especially in patients with cirrhosis.

  16. [Alveolar haemorrhage and hepatitis virus C related mixed cryoglobulinemia. Report of three cases].

    PubMed

    Perelló Carbonel, R; Supervía Caparrós, A; Nolla Salas, J; Vázquez Sánchez, A; Torrente Segarra, V; Gutiérrez Cebollada, J

    2005-11-01

    Hepatitis C virus -related mixed cryoglobulinemia is a recognised entity. Renal and pulmonary involvements are severe potential complications of this disease. Alveolar haemorrhage is a form of pulmonary complication. The clinical features of the alveolar haemorrhage can mimic other pulmonary diseases. We present three patients with hepatitis C virus-related mixed cryoglobulinemia associated to pulmonary symptoms that turned to be caused by an alveolar haemorrhage. The first patient was a 71-year old woman that was admitted because of hemoptysis and severe dyspnea that required mechanical ventilation. Although a pneumonia was the initial diagnoses, an alveolar haemorrhage was soon suspected based on the persistence of the pulmonary radiological infiltrates despite an adequate empirical antibiotic treatment and the presence of a progressive anemization. A fibrobronchoscopy, performed 48 hours after treatment was begun, revealed the presence of a 6% of hemosiderophages. The second patient was a 64 years old woman admitted because of dyspnea, vasculitic cutaneous lesions in gluteus and kidney failure. A severe pneumonia was suspected, antibiotic treatment was started and again the patient needed mechanical ventilation. The fibrobronchoscopy demonstrated the existence of a 60% of hemosiderophages. The third case describes a 67 year old woman that complained of fever, dyspnea and right chest pain. Similarly to the previous cases a severe pneumonia was the initial diagnoses, the patient needed to be transferred to the intensive care unit and mechanical ventilation was finally required. The fibrobronchoscopy showed remains of blood suggestive of an alveolar haemorrhage.

  17. An experimental type II mixed cryoglobulinemia with renal glomerulopathy in ICR mice triggered by Capillaria hepatica infection.

    PubMed

    Aihara, Naoyuki; Chambers, James Kenn; Hosono, Kei; Kamiie, Junichi; Shirota, Kinji

    2011-12-01

    Type II mixed cryoglobulinemia is characterized by systemic vasculitis with deposition of cryoprecipitatable-immunoglobulins containing rheumatoid factor. Pathogenesis of type II mixed cryoglobulinemia has not yet been completely clarified because of the lack of an experimental animal. Here, we report an animal model of type II mixed cryoglobulinemia that is induced by experimental infection with Capillaria hepatica in ICR mice. Capillaria hepatica is a nematode that causes necrotic hepatitis in several mammals. In this study, mice experimentally infected with C. hepatica eggs developed cryoglobulinemia at 20 and 30 days post injection. Using immunological analysis, cryoglobulinemia in infected mice was classified as type II mixed cryoglobulinemia by detection of monoclonal IgM rheumatoid factor and IgA in the cryoprecipitate of serum. Using immunofluorescence, we observed an increase in the number of double-positive cells for µ heavy and κ light chains of immunoglobulin in the spleens of infected mice. Histopathologically, this model was characterized by glomerulopathy associated with intense deposition of IgM and IgA filling in capillary lumina. Ultrastructural analysis showed that glomerular deposits consisted of stacks of twisted microtubular structures. These serological and histological features resembled those of type II mixed cryoglobulinemia in human. This is the first experimental animal model of type II mixed cryoglobulinemia that will enable detailed studies on the pathogenesis of cryoglobulinemia.

  18. Thyroid involvement in hepatitis C - associated mixed cryoglobulinemia.

    PubMed

    Fallahi, Poupak; Ferrari, Silvia Martina; Giuggioli, Dilia; Manfredi, Andreina; Mancusi, Caterina; Fabiani, Silvia; Centanni, Marco; Marchi, Santino; Ferri, Clodoveo; Antonelli, Alessandro

    2014-01-01

    The prevalence and clinical features of thyroid involvement in patients with hepatitis C virus-associated mixed cryoglobulinemia (MC+HCV) have been reviewed. A PubMed Medline search was conducted through December 2011 to identify all studies that reported thyroid involvement in MC+HCV patients. Reference lists of the papers initially detected were manually searched to identify additional relevant reports. Studies had to contain sufficient and clear information to be included. In MC+HCV patients, the following thyroid autoimmune abnormalities were significantly more frequent than in controls: high levels of serum anti-thyroperoxidase autoantibody (AbTPO); high levels of serum AbTPO and/or anti-thyroglobulin autoantibody; humoral and ultrasonographical signs of thyroid autoimmunity (35% vs 16%); prevalence of subclinical hypothyroidism (11% vs 2%). Also, the prevalence of papillary thyroid cancer has been found higher in MC+HCV patients than in controls, in particular in patients with autoimmune thyroiditis. The involvement of T helper 1 immunity and chemokine (C-X-C motif) ligand 10 (CXCL10) may be the pathogenetic basis of the association between MC+HCV and thyroid autoimmunity. These results show a high prevalence of thyroid disorders in patients with MC+HCV and point to the need for careful monitoring of thyroid function in these patients.

  19. Cutaneous lesions and finger clubbing uncovering hypocomplementemic urticarial vasculitis and hepatitis C with mixed cryoglobulinemia.

    PubMed

    Pinto-Almeida, Teresa; Caetano, Mónica; Alves, Rosário; Selores, Manuela

    2013-01-01

    Urticarial vasculitis is a rare clinicopathologic entity characterized by urticarial lesions that persist for more than 24 hours and histologic features of leukocytoclastic vasculitis. Patients can be divided into normocomplementemic or hypocomplementemic. The authors report the case of a healthy 49-year-old woman with a 1-year history of highly pruritic generalized cutaneous lesions and finger clubbing. Laboratory tests together with histopathologic examination allowed the diagnosis of hypocomplementemic urticarial vasculitis, chronic hepatitis C and type II mixed cryoglobulinemia. The patient started symptomatic treatment and was referred to a gastroenterologist for management of the hepatitis C, with progressive improvement of the skin condition. The development of hypocomplementemic urticarial vasculitis in the context of chronic hepatitis C is exceedingly rare and possible pathogenic mechanisms are discussed.

  20. Cutaneous lesions and finger clubbing uncovering hypocomplementemic urticarial vasculitis and hepatitis C with mixed cryoglobulinemia*

    PubMed Central

    Pinto-Almeida, Teresa; Caetano, Mónica; Alves, Rosário; Selores, Manuela

    2013-01-01

    Urticarial vasculitis is a rare clinicopathologic entity characterized by urticarial lesions that persist for more than 24 hours and histologic features of leukocytoclastic vasculitis. Patients can be divided into normocomplementemic or hypocomplementemic. The authors report the case of a healthy 49-year-old woman with a 1-year history of highly pruritic generalized cutaneous lesions and finger clubbing. Laboratory tests together with histopathologic examination allowed the diagnosis of hypocomplementemic urticarial vasculitis, chronic hepatitis C and type II mixed cryoglobulinemia. The patient started symptomatic treatment and was referred to a gastroenterologist for management of the hepatitis C, with progressive improvement of the skin condition. The development of hypocomplementemic urticarial vasculitis in the context of chronic hepatitis C is exceedingly rare and possible pathogenic mechanisms are discussed. PMID:24474109

  1. Interferon-alpha treatment of hepatitis C virus-associated mixed cryoglobulinemia.

    PubMed

    Polzien, F; Schott, P; Mihm, S; Ramadori, G; Hartmann, H

    1997-07-01

    Chronic hepatitis C virus infection is frequently associated with mixed cryoglobulinemia. The efficacy of interferon-alpha treatment in the presence of cryoglobulinemia, particularly the rate of sustained responders, has not yet been well defined. Fifty-nine consecutive patients with chronic HCV infection were studied prospectively with regard to the presence of cryoglobulinemia and their biochemical and virological response to interferon-alpha2a therapy. Cryoglobulins were detected in sera of 23 patients. For this latter group of patients, significant differences were found compared to the 36 patients without cryoglobulinemia, i.e. the prevalence of female sex was higher, the duration of liver disease was longer and distinctive laboratory abnormalities, e.g. higher rheumatoid factor activity, were noted as well as a higher prevalence of cirrhosis. The distribution of HCV genotypes and serum HCV RNA titers was similar in the two groups. Interferon-alpha treatment regimens were not different regarding mean cumulative dose and mean duration of therapy. The response to therapy was almost identical, i.e. 35% of patients with cryoglobulinemia showed a sustained response compared to 22% of patients without cryoglobulinemia. The percentages of patients showing a relapse or breakthrough were similar in both groups. Pre-treatment viremia levels were higher in non-responders compared to sustained responders. Non-responders appeared to be more frequent among patients infected with genotypes 1a and 1b, especially among male patients without cryoglobulinemia. The presence of cryoglobulinemia per se in chronic HCV-infected patients does not adversely affect the outcome of interferon-alpha therapy, including the rate of sustained response.

  2. Type III mixed cryoglobulinemia and antiphospholipid syndrome in a patient with partial DiGeorge syndrome.

    PubMed

    Chang, Alice D; Tachdjian, Raffi; Gallagher, Kerry; McCurdy, Deborah K; Lassman, Charles; Stiehm, E Richard; Yadin, Ora

    2006-01-01

    We studied a 14 year-old boy with partial DiGeorge syndrome (DGS), status post complete repair of Tetralogy of Fallot, who developed antiphospholipid syndrome (APS) and type III mixed cryoglobulinemia. He presented with recurrent fever and dyspnea upon exertion secondary to right pulmonary embolus on chest computed tomography (CT). Coagulation studies revealed homozygous methylene tetrahydrofolate reductase 677TT mutations, elevated cardiolipin IgM antibodies, and elevated beta(2)-glycoprotein I IgM antibodies. Infectious work-up revealed only positive anti-streptolysin O (ASO) and anti-DNAse B titers. Autoimmune studies showed strongly positive anti-platelet IgM, elevated rheumatoid factor (RF), and positive cryocrit. Renal biopsy for evaluation of proteinuria and hematuria showed diffuse proliferative glomerulonephritis (DPGN) with membranoproliferative features consistent with cryoglobulinemia. Immunofixation showed polyclonal bands. Our patient was treated successfully with antibiotics, prednisone, and mycophenolate mofetil (MMF). This is the first report of a patient with partial DGS presenting with APS and type III mixed cryoglobulinemia possibly due to Streptococcal infection.

  3. Type III Mixed Cryoglobulinemia and Antiphospholipid Syndrome in a Patient With Partial DiGeorge Syndrome

    PubMed Central

    Chang, Alice D.; Tachdjian, Raffi; Gallagher, Kerry; McCurdy, Deborah K.; Lassman, Charles; Stiehm, E. Richard; Yadin, Ora

    2006-01-01

    We studied a 14 year-old boy with partial DiGeorge syndrome (DGS), status post complete repair of Tetralogy of Fallot, who developed antiphospholipid syndrome (APS) and type III mixed cryoglobulinemia. He presented with recurrent fever and dyspnea upon exertion secondary to right pulmonary embolus on chest computed tomography (CT). Coagulation studies revealed homozygous methylene tetrahydrofolate reductase 677TT mutations, elevated cardiolipin IgM antibodies, and elevated β2-glycoprotein I IgM antibodies. Infectious work-up revealed only positive anti-streptolysin O (ASO) and anti-DNAse B titers. Autoimmune studies showed strongly positive anti-platelet IgM, elevated rheumatoid factor (RF), and positive cryocrit. Renal biopsy for evaluation of proteinuria and hematuria showed diffuse proliferative glomerulonephritis (DPGN) with membranoproliferative features consistent with cryoglobulinemia. Immunofixation showed polyclonal bands. Our patient was treated successfully with antibiotics, prednisone, and mycophenolate mofetil (MMF). This is the first report of a patient with partial DGS presenting with APS and type III mixed cryoglobulinemia possibly due to Streptococcal infection. PMID:17162366

  4. Systematic review of mixed cryoglobulinemia associated with hepatitis E virus infection: association or causation?

    PubMed

    Bazerbachi, Fateh; Leise, Michael D; Watt, Kymberly D; Murad, M Hassan; Prokop, Larry J; Haffar, Samir

    2017-08-01

    Background and aim: Mixed cryoglobulinemia (MC) has been associated with several viral infections, and chronic hepatitis C is recognized as a major cause. MC associated with hepatitis E virus (HEV) has been described and little is known about this rare association. The aim of this study is to perform a systematic review of MC associated with HEV, and examine the presence of a causal relationship. Methods: An experienced librarian conducted a search of databases from each database's inception to 12 December 2016 based on a priori criteria. The risk of bias was assessed, and Hill's criteria were applied to determine causality. Results: Five publications met inclusion criteria, with a total of 15 cases. Three studies had low, one low to moderate and one moderate risk of bias. Median age was 43 years, and all patients came from Western Europe. Two patients were immunocompetent, while 13 were immunosuppressed, post solid organ transplant and had chronic hepatitis E. Renal involvement was observed in seven patients, mild to moderately severe cryoglobulinemic disease in one patient and severe cryoglobulinemic disease in three patients. One patient improved spontaneously, and another was treated with immunosuppressant reduction leading to viral clearance. Ten patients treated with peg-interferon or ribavirin for 3 months achieved loss of cryoglobulinemia and end-of-treatment response, but sustained virologic response was reported and achieved in two. Immunosuppressant achieved loss of cryoglobulinemia in three patients. One case of chronic renal failure, three cases of end-stage renal disease and one death were observed. Five of the nine Hill's criteria were fulfilled. Conclusion: MC has been described with HEV infection. A causal relationship between HEV infection and cryoglobulinemia is highly probable.

  5. Systematic review of mixed cryoglobulinemia associated with hepatitis E virus infection: association or causation?

    PubMed Central

    Leise, Michael D.; Watt, Kymberly D.; Murad, M. Hassan; Prokop, Larry J.; Haffar, Samir

    2017-01-01

    Abstract Background and aim: Mixed cryoglobulinemia (MC) has been associated with several viral infections, and chronic hepatitis C is recognized as a major cause. MC associated with hepatitis E virus (HEV) has been described and little is known about this rare association. The aim of this study is to perform a systematic review of MC associated with HEV, and examine the presence of a causal relationship. Methods: An experienced librarian conducted a search of databases from each database’s inception to 12 December 2016 based on a priori criteria. The risk of bias was assessed, and Hill’s criteria were applied to determine causality. Results: Five publications met inclusion criteria, with a total of 15 cases. Three studies had low, one low to moderate and one moderate risk of bias. Median age was 43 years, and all patients came from Western Europe. Two patients were immunocompetent, while 13 were immunosuppressed, post solid organ transplant and had chronic hepatitis E. Renal involvement was observed in seven patients, mild to moderately severe cryoglobulinemic disease in one patient and severe cryoglobulinemic disease in three patients. One patient improved spontaneously, and another was treated with immunosuppressant reduction leading to viral clearance. Ten patients treated with peg-interferon or ribavirin for 3 months achieved loss of cryoglobulinemia and end-of-treatment response, but sustained virologic response was reported and achieved in two. Immunosuppressant achieved loss of cryoglobulinemia in three patients. One case of chronic renal failure, three cases of end-stage renal disease and one death were observed. Five of the nine Hill’s criteria were fulfilled. Conclusion: MC has been described with HEV infection. A causal relationship between HEV infection and cryoglobulinemia is highly probable. PMID:28852522

  6. No evidence of Polyomavirus and EBV infections in Italian patients with mixed cryoglobulinemia infected chronically with HCV.

    PubMed

    Comar, Manola; Zanotta, Nunzia; Del Savio, Rossella; Vascotto, Fulvia; Calabrese, Nadia; Zorat, Francesca; Pozzato, Gabriele

    2014-04-01

    Mixed cryoglobulinemia is a lymphoproliferative disorder associated with hepatitis C virus (HCV). In patients chronically affected by HCV the prevalence of mixed cryoglobulinemia is variable ranging from 0% to 56%. To verify whether polyomaviruses (PyV) play a role in this disorder a total of 222 blood samples from 63 HCV chronic patients, 43 with mixed cryoglobulinemia, 59 chronic lymphocytic leukemia, 50 polytransfused patients, and 50 blood donors were evaluated for Merkel (MCPyV), BKV, JCV, and SV40. EBV was additionally included in the analysis since association with this disorder has been reported. Mixed cryoglobulinemia patients infected chronically with HCV resulted negative for both PyV and EBV. MCPyV was found in 1 subject with Merkel Cell Carcinoma, in 10% of polytransfused and in 10% of blood donors while EBV was detected in 22% of polytransfused, 10% of B-cell lymphatic leukemia patients and 4% of blood donors (P < 0.01). Taken together, the absence of PyV and EBV in HCV-mixed cryoglobulinemia patients seems to exclude a direct involvement of these viruses in the pathogenesis of this disease while the presence of MCPyV in healthy individuals, at the same rate as in polytransfused patients, may reinforce data on a minimal role of this virus in other human pathologies.

  7. [Mixed type-II cryoglobulinemia associated with a chronic hepatitis C virus infection].

    PubMed

    Suárez, A; Vallina, E; Navascués, C A; Rodríguez, M; Otero, L; Sotorrío, N G; San Román, F; Rodrigo, L

    1993-04-01

    We describe the case of a patient with non A-non B post-transfusional cirrhosis and type-II mixed cryoglobulinemia, who showed in relation with said processes several acute symptoms of vasculitis, polyarthritis, pericarditis and autoimmune hemolytic anemia, finally dying due to an advanced hepatocellular insufficiency. In this patient the determination of antibodies against hepatitis C virus (anti-HCV) was positive, that is why we assume a possible relationship between both processes and the first literature references, after the clonation of the hepatitis C virus (HCV) genome, are reviewed.

  8. Hepatitis C Virus-related Mixed Cryoglobulinemia: Pathogenesis, Clinica Manifestations, and New Therapies.

    PubMed

    Schamberg, Neal J; Lake-Bakaar, Gerond V

    2007-09-01

    Within the past decade, it has been recognized that a majority of patients with essential mixed cryoglobulinemia (MC) are chronically infected with hepatitis C virus (HCV). Although the underlying mechanisms have not been fully elucidated, cryoglobulin formation is clearly linked to the attempt of the host to clear the significant quantities of virions generated daily by the chronic infection. This review summarizes the current understanding of the relationship between chronic HCV infection and the development of MC, and discusses the interaction between the immune system and HCV and how this interaction can lead to the development of lymphoproliferative disorders.

  9. A case of essential mixed cryoglobulinemia and associated acquired von-Willebrand disease treated with rituximab.

    PubMed

    Pasa, Semir; Altintas, Abdullah; Cil, Timucin; Danis, Ramazan; Ayyildiz, Orhan; Muftuoglu, Ekrem

    2009-02-01

    Current treatment options of essential mixed cryoglobulinemia (EMC); include immunosuppressive approaches, such as corticosteroids, cyclophosphamide, plasma exchange, other cytotoxic drugs in moderate to severe manifestations. Some controlled studies have been carried out to assess the efficacy of anti-CD20 monoclonal antibody, rituximab in patients with hepatitis C (HCV) related cryoglobulinemia (CG) and in patients with autoimmune disorders. Recent trials and some case reports demonstrate a beneficial role for rituximab in HCV related mixed CG. Although, the published evidence for treatment of EMC with rituximab is restricted to case reports, which have shown positive results. Several diseases include lymphoproliferative and myeloproliferative disorders, solid tumors, immunological disorders, cardiovascular disorders and some drugs associated with acquired von Willebrand disease (avWD). CG, which is a kind of immune complex disease, may be related with development of autoantibodies to various autoantigens. In this present case report, we showed the efficacy of rituximab in a 21-year-old female patient, suffered from neuropathy and arthralgia related with EMC, and developed avWD, presented with mucosal bleeding associated with CG. von Willebrand factor activity of our patient also increased with controlling the underlying disease, EMC by rituximab. This case demonstrate that rituximab may be an effective treatment option in EMC and avWD mainly related to CG.

  10. Efficacy and Safety of Direct Acting Antivirals for the Treatment of Mixed Cryoglobulinemia.

    PubMed

    Emery, Joel S; Kuczynski, Magdalena; La, Danie; Almarzooqi, Saeed; Kowgier, Matthew; Shah, Hemant; Wong, David; Janssen, Harry L A; Feld, Jordan J

    2017-08-01

    Mixed cryoglobulinemia is strongly associated with hepatitis C virus (HCV) infection and ranges from being asymptomatic to causing life-threatening vasculitis. In those with symptoms, treatment with pegylated interferon (pegIFN) and ribavirin (RBV) reduces mortality. However, few data are available on the safety and efficacy of antiviral therapy with direct acting antivirals (DAAs) in the treatment of HCV-related cryoglobulinemia. Patients treated for HCV-related cryoglobulinemia with DAA±pegIFN were retrospectively evaluated at a tertiary care center. Primary outcomes were virological, immunological, and clinical response. Complete (normalization), partial (>50% reduction), or non-response (<50% reduction) were used to describe change in cryocrit or vasculitic manifestations at week 12 post treatment. Side effects, hospitalizations, and decompensating events were recorded. Eighteen symptomatic and 65 asymptomatic patients were reviewed (61% male, median age 58 years) including 10 with severe/life-threatening vasculitis. Sixty-six (79.5%) patients received pegIFN-free therapy. Sustained virological response (SVR) was attained in 16 (88.9%) symptomatic and 59 (90.8%) asymptomatic patients. Cryoglobulins disappeared in 5 (29.4%) symptomatic and 27 (52.9%) asymptomatic patients. Of symptomatic patients with SVR, clinical response was complete in 7 (38.8%) and partial response in 4 (22.2%). Of the 5 viral relapsers, 1 had a complete response during therapy with no symptomatic recurrence, while the other patients had no clinical response. Among 7 with severe vasculitis, 6 achieved SVR but only 1 had a complete clinical response, with 3 showing a partial response and 2 showing no improvement. All four with life-threatening vasculitis required plasmapheresis and three received rituximab. All achieved SVR leading to partial clinical response in two, but no response in two. Skin manifestations (39% reduction) were most likely to completely resolve with lower responses seen

  11. Cryoglobulinemia related to hepatitis C virus infection.

    PubMed

    Dore, Maria Pina; Fattovich, Giovanna; Sepulveda, Antonia R; Realdi, Giuseppe

    2007-04-01

    A causal link among hepatitis C virus (HCV) infection and essential mixed cryoglobulinemia, cryoglobulinemic glomerulonephritis, and vasculitis is strongly supported. HCV triggers autoimmune response in predisposed individuals that manifests as organ-specific and non-organ-specific autoantibodies and as polyclonal/monoclonal rheumatoid factor, which has a central role in causing damaging cryoglobulin and immune complex tissue levels. Immunologic events are mainly induced by HCV infection persistence, with excessive immune stimulation. Humoral immune dysfunction leads to autoantibodies and rheumatoid factor production with cryoglobulinemia, glomerulonephritis, vasculitis, neuropathy, and probably thyroiditis, and arthritis in rare cases. Cellular immune dysfunction leads to lymphocytic infiltration, proliferation, and cytokine production. Pegylated (or not) interferon-alpha in combination with ribavirin appears to be the treatment of choice for patients with symptomatic essential mixed cryoglobulinemia with or without glomerulonephritis. Novel treatment with rituximab is promising.

  12. Complex regional pain syndrome (reflex sympathetic dystrophy) in a patient with essential mixed cryoglobulinemia and chronic hepatitis C.

    PubMed

    Bant, Ankur; Hurowitz, Bertram; Hassan, Nadeem; Du, Van Thiel; Nadir, Abdul

    2007-02-01

    Essential mixed cryoglobulinemia (EMC) is a common extra-hepatic manifestation of hepatitis C virus (HCV). Complex Regional Pain Syndrome type I (CRPS) or Reflex sympathetic dystrophy (RSD) has never been reported in association with HCV. This is the first case report of RSD in a patient with HCV related cirrhosis and EMC.

  13. Thyroid Involvement in Hepatitis C Virus-Infected Patients with/without Mixed Cryoglobulinemia.

    PubMed

    Ferri, Clodoveo; Colaci, Michele; Fallahi, Poupak; Ferrari, Silvia Martina; Antonelli, Alessandro; Giuggioli, Dilia

    2017-01-01

    Thyroid involvement is a common condition that can be recorded during the natural course of different systemic rheumatic diseases, including the mixed cryoglobulinemia (MC) syndrome or cryoglobulinemic vasculitis. MC is triggered by hepatitis C virus (HCV) chronic infection in the majority of cases; it represents the prototype of autoimmune-lymphoproliferative disorders complicating a significant proportion of patients with chronic HCV infection. HCV is both hepato- and lymphotropic virus responsible for a great number of autoimmune/lymphoproliferative and/or neoplastic disorders. The complex of HCV-related hepatic and extrahepatic manifestations, including MC and thyroid involvement, may be termed "HCV syndrome." Here, we describe the prevalence and clinico-serological characteristics of thyroid involvement, mainly autoimmune thyroiditis and papillary thyroid cancer, in patients with HCV syndrome with or without cryoglobulinemic vasculitis.

  14. Molecular Signatures of Hepatitis C Virus (HCV)-Induced Type II Mixed Cryoglobulinemia (MCII)

    PubMed Central

    Sautto, Giuseppe; Mancini, Nicasio; Clementi, Massimo; Burioni, Roberto

    2012-01-01

    The role of hepatitis C virus (HCV) infection in the induction of type II mixed cryoglobulinemia (MCII) and the possible establishment of related lymphoproliferative disorders, such as B-cell non-Hodgkin lymphoma (B-NHL), is well ascertained. However, the molecular pathways involved and the factors predisposing to the development of these HCV-related extrahepatic complications deserve further consideration and clarification. To date, several host- and virus-related factors have been implicated in the progression to MCII, such as the virus-induced expansion of selected subsets of B-cell clones expressing discrete immunoglobulin variable (IgV) gene subfamilies, the involvement of complement factors and the specific role of some HCV proteins. In this review, we will analyze the host and viral factors taking part in the development of MCII in order to give a general outlook of the molecular mechanisms implicated. PMID:23202510

  15. [Mixed cryoglobulinemia and related immunological disorders after hepatic transplantation for hepatitis C cirrhosis. Case report].

    PubMed

    Sarmiento, Elizabeth; Rodríguez Molina, Juan José; Carbone, Javier

    2004-01-01

    Cryoglobulinemia may be found in up to 30% of patients that had received liver transplants after hepatitis C virus (HCV) cirrhosis. Three types of cryoglobulinemia are recognized: type I, composed of monoclonal immunoglobulins associated with lymphoproliferative diseases and myeloma; type II cryoglobulinemia are comprised of a monoclonal component which has rheumatoid factor activity and hence binds to polyclonal immunoglobulins (in certain parts of the world have been found to be associated with hepatitis C infection); and type III cryoglobulinemia consist exclusively of polyclonal immunoglobulins with rheumatoid factor activity (associated with connective tissue diseases and chronic infections including hepatitis C). Immunocompetence, autoimmunity and clonal expansion of B cell lymphocytes have not been analysed simultaneously in previous reports of patients with cryoglobulinemia after liver transplantation. We here describe immunological abnormalities associated with cryoglobulinemia in a patient who had received liver transplant for HCV cirrhosis. In addition, in the present work HCV RNA determination was performed directly in the cryocrit and not only in peripheral blood. We have observed enrichment of HCV RNA in the cryoprecipitates which might be a better demonstration of the possible role of HCV in the pathogenesis of the cryoglobulinemia.

  16. Mixed cryoglobulinemia-associated Sjögren’s syndrome leading to spontaneous rupture of the kidney: a case report

    PubMed Central

    Haddiya, Intissar; Hamzaoui, Hakim; Alhamany, Zitouna; Berkchi, Fatime-zohra; Rhou, Hakima; Benamar, Loubna; Ouzeddoun, Naima; Bayahia, Rabea

    2016-01-01

    Background Spontaneous rupture of the kidney is uncommon and is mainly caused by renal tumors. Only a few cases are caused by vasculitis. We report here the first case of spontaneous rupture of kidney resulting from mixed cryoglobulinemia. Case presentation A 44-year-old man presented with sudden onset of fever, acute pulmonary edema, left flank abdominal pain unassociated with trauma, and rapidly progressive renal failure requiring dialysis. Computed tomography of the abdomen revealed a large perirenal hematoma of the left kidney. During conservative surgery, the patient underwent renal biopsy that showed renal vasculitis and membranoproliferative glomerulonephritis with intracapillary microthrombi. Tests were positive for mixed cryoglobulinemia caused by Sjögren’s syndrome. The patient was better after immunosuppressive therapy, with the disappearance of clinical symptoms and the recovery of baseline renal function. Conclusion We report on this case and discuss a possible link between spontaneous rupture of kidney and mixed cryoglobulinemia-associated Sjögren’s syndrome. PMID:27042145

  17. Infectious serologies and autoantibodies in hepatitis C and autoimmune disease-associated mixed cryoglobulinemia.

    PubMed

    Lidar, Merav; Lipschitz, Noga; Agmon-Levin, Nancy; Langevitz, Pnina; Barzilai, Ori; Ram, Maya; Porat-Katz, Bat-Sheba; Bizzaro, Nicola; Damoiseaux, Jan; Tervaert, Jan Willem Cohen; deVita, Salvatore; Bombardieri, Stefano; Shoenfeld, Yehuda

    2012-04-01

    Mixed cryoglobulinemia (MC) syndrome is an immune complex-mediated vasculitis characterized by the clinical triad of purpura, weakness, and arthralgias, the morbidity of which is mainly related to kidney and peripheral nervous system dysfunction as well as to the development of a secondary lymphoma (Ferri et al. Autoimmun Rev 7:114-120, 2007, Lidar et al. Ann N Y Acad Sci 1173:649-657, 2009, Trejo et al. Semin Arthritis Rheum 33:19-28, 2003). MC is associated with infectious and systemic disorders, principally autoimmune and lymphoproliferative diseases. Since the 1990s, a striking association (>90%) between MC and hepatitis C virus (HCV) infection has been established (Ferri and Bombardieri 2004; Pascual et al. J Infect Dis 162:569-570, 1990). However, information regarding the etiopathogenesis of HCV-negative MC is scant (Mascia et al. Dig Liver Dis 39:61-64, 2007). We hereby present our findings, as well as previously published data, regarding the presence of antibodies against infectious agents and autoantibodies in patients with MC in an attempt to establish novel associations which may shed light on the etiopathogenesis of this disease.

  18. Clonal expansion of immunoglobulin M+CD27+ B cells in HCV-associated mixed cryoglobulinemia

    PubMed Central

    Charles, Edgar D.; Green, Rashidah M.; Marukian, Svetlana; Talal, Andrew H.; Lake-Bakaar, Gerond V.; Jacobson, Ira M.; Rice, Charles M.

    2008-01-01

    Hepatitis C virus (HCV) is associated with B-cell lymphoproliferative disorders such as mixed cryoglobulinemia (MC) and B-cell non-Hodgkin lymphoma (B-NHL). The pathogenesis of these disorders remains unclear, and it has been proposed that HCV drives the pro-liferation of B cells. Here we demonstrate that certain HCV+MC+ subjects have clonal expansions of immunoglobulin M (IgM)+κ+IgDlow/−CD21lowCD27+ B cells. Using RT-PCR to amplify Ig from these singly sorted cells, we show that these predominantly rheumatoid factor-encoding VH1-69/JH4 and Vκ3-20 gene segment-restricted cells have low to moderate levels of somatic hypermutations. Ig sequence analysis suggests that antigen selection drives the generation of mutated clones. These findings lend further support to the notion that specific antigenic stimulation leads to B-cell proliferation in HCV MC and that chronic B-cell stimulation may set the stage for malignant transformation and the development of B-NHL. The finding that these hypermutated, marginal zone-like IgM+CD27+ B cells are clonally expanded in certain subjects with MC offers insight into mechanisms of HCV-associated MC and B-cell malignancy. This study was registered at www.clinicaltrials.gov as NCT00219999. PMID:17942751

  19. Incidence of thyroid disorders in mixed cryoglobulinemia: Results from a longitudinal follow-up.

    PubMed

    Fallahi, Poupak; Ferrari, Silvia Martina; Ruffilli, Ilaria; Elia, Giusy; Giuggioli, Dilia; Colaci, Michele; Ferri, Clodoveo; Antonelli, Alessandro

    2016-07-01

    No study has evaluated the incidence of new cases of thyroid autoimmunity (AT) and dysfunction (TD) in hepatitis C-associated mixed cryoglobulinemia (MC) patients. We aimed to evaluate the incidence of new cases of AT and TD in a wide group of MC patients vs. age- and gender-matched controls from the same geographic area. After exclusion of MC patients with TD at the initial evaluation, the appearance of new cases of TD was evaluated in 112 MC patients and 112 matched controls, with similar iodine intake (median follow-up 67months in MC vs. 78 in controls). A high incidence (P<0.05) of new cases of hypothyroidism, TD, anti-thyroperoxidase antibody (AbTPO) positivity, appearance of a hypoechoic thyroid pattern, and thyroid autoimmunity in MC patients vs. controls was shown. A logistic regression analysis showed that in MC, the appearance of hypothyroidism was related to female gender, a borderline high initial thyroid-stimulating hormone (TSH), AbTPO positivity, a hypoechoic, and small thyroid. In conclusion, we show a high incidence of new cases of AT and TD in MC patients. MC patients at high risk (female gender, a borderline high initial TSH, AbTPO positivity, a hypoechoic, and small thyroid) should have periodically thyroid function follow-up. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Hepatitis C virus-related mixed cryoglobulinemia: Is genetics to blame?

    PubMed Central

    Gragnani, Laura; Fognani, Elisa; Piluso, Alessia; Zignego, Anna Linda

    2013-01-01

    Mixed cryoglobulinemia (MC) is the extrahepatic manifestation most strictly correlated with hepatitis C virus (HCV) infection; it is a benign autoimmune and lymphoproliferative disorder that evolves to lymphoma in 5%-10% of cases. MC is reputed to be a multistep and multifactorial process whose pathogenicity is still poorly understood. It is still unknown why only some chronically infected HCV patients develop MC and only some of these exhibit systemic symptoms (MC syndrome). Several studies have investigated the pathogenetic basis of MC and the most recent ones suggest that the virus is able to trigger such a disorder only in the presence of genetic factors that are still unknown. Here, we try to clarify the complex relationship between HCV-related MC and the host’s genetic background. The data that we report are heterogeneous and sometimes even conflicting. Therefore, large, multicenter studies are clearly needed. The identification of a characteristic genetic signature of cryoglobulinemic patients would be an important step toward a personalized approach in their clinical care. The new wide-ranging genomics technologies will hopefully help to resolve these complex issues. PMID:24379615

  1. Immunopathogenesis of HCV-related endocrine manifestations in chronic hepatitis and mixed cryoglobulinemia.

    PubMed

    Antonelli, Alessandro; Ferri, Clodoveo; Ferrari, Silvia Martina; Colaci, Michele; Fallahi, Poupak

    2008-10-01

    Hepatitis C Virus (HCV) is known to be responsible for both hepatic and extrahepatic diseases (HCV-related extrahepatic diseases = HCV-EHDs). The most important systemic HCV-EHDs are mixed cryoglobulinemia and lymphoproliferative disorders, while the most frequent and clinically important endocrine HCV-EHDs are thyroid disorders and type 2 diabetes mellitus (T2D). From a meta-analysis of the literature a significant association between HCV infection and thyroid autoimmunity and hypothyroidism has been reported. A high prevalence of thyroid cancer has been reported, too. Furthermore, several clinical epidemiologic studies have reported that HCV infection is associated to T2D. Many studies have linked Th1 immune response with HCV infection, thyroid autoimmunity, or diabetes. These findings suggest that a possible common immunological Th1 pattern could be the pathophysiological base of the association of HCV-EHDs, with thyroid autoimmunity and T2D. In fact, HCV infection of thyrocytes or beta-cells may act by upregulating CXCL10 secretion in these cells that is responsible for Th1 lymphocyte recruitment. Th1 response leads to increased IFNgamma and TNFalpha production that in turn stimulates CXCL10 secretion by the target cells, thus perpetuating the immune cascade. This process may lead to the appearance of thyroid autoimmune disorders or T2D in genetically predisposed subjects.

  2. Hepatitis C virus-related mixed cryoglobulinemia: is genetics to blame?

    PubMed

    Gragnani, Laura; Fognani, Elisa; Piluso, Alessia; Zignego, Anna Linda

    2013-12-21

    Mixed cryoglobulinemia (MC) is the extrahepatic manifestation most strictly correlated with hepatitis C virus (HCV) infection; it is a benign autoimmune and lymphoproliferative disorder that evolves to lymphoma in 5%-10% of cases. MC is reputed to be a multistep and multifactorial process whose pathogenicity is still poorly understood. It is still unknown why only some chronically infected HCV patients develop MC and only some of these exhibit systemic symptoms (MC syndrome). Several studies have investigated the pathogenetic basis of MC and the most recent ones suggest that the virus is able to trigger such a disorder only in the presence of genetic factors that are still unknown. Here, we try to clarify the complex relationship between HCV-related MC and the host's genetic background. The data that we report are heterogeneous and sometimes even conflicting. Therefore, large, multicenter studies are clearly needed. The identification of a characteristic genetic signature of cryoglobulinemic patients would be an important step toward a personalized approach in their clinical care. The new wide-ranging genomics technologies will hopefully help to resolve these complex issues.

  3. Restoration of peripheral immune homeostasis after rituximab in mixed cryoglobulinemia vasculitis.

    PubMed

    Saadoun, David; Rosenzwajg, Michelle; Landau, Dan; Piette, Jean Charles; Klatzmann, David; Cacoub, Patrice

    2008-06-01

    Rituximab, an anti-CD20 monoclonal antibody, has been used to treat autoimmune disorders such as mixed cryoglobulinemia (MC). However, its mechanisms of action as well as the effects on cellular immunity remain poorly defined. We investigated the changes of peripheral blood B- and T-cell subsets, the clonal VH1-69 cells, as well as the cytokine profile following rituximab therapy. The study involved 21 patients with hepatitis C-related MC who received rituximab, of whom 14 achieved a complete response. Compared with healthy and hepatitis C virus (HCV) controls, pretreatment abnormalities in MC patients included a decreased percentage of naive B cells (P < .05) and CD4(+)CD25(+)FoxP3(+) regulatory T cells (P = .02) with an increase in memory B cells (P = .03) and plasmablasts (P < .05). These abnormalities were reverted at 12 months after rituximab. Clonal VH1-69(+) B cells dramatically decreased following treatment (32% +/- 6% versus 8% +/- 2%, P = .01). Complete responders of rituximab exhibited an expansion of regulatory T cells (P < .01) accompanied with a decrease in CD8(+) T-cell activation (P < .01) and decreased production of interleukin 12 (IL-12; P = .02) and interferon-gamma (IFN-gamma; P = .01). Our findings indicate that in patients with MC, response to B-cell depletion induced by rituximab effectively normalizes many of the disturbances in peripheral B- and T-lymphocyte homeostasis.

  4. Systemic vasculitis in patients with hepatitis C virus infection with and without detectable mixed cryoglobulinemia.

    PubMed

    Terrier, Benjamin; Sène, Damien; Dechartres, Agnès; Saadoun, David; Ortonne, Nicolas; Rouvier, Philippe; Musset, Lucile; Rigon, Matthieu Resche; Maisonobe, Thierry; Cacoub, Patrice

    2011-01-01

    to describe hepatitis C virus (HCV)-related systemic vasculitis in patients without detectable mixed cryoglobulinemia (MC) and to compare them to typical cases of HCV-MC vasculitis. twelve HCV RNA+ patients with histologically proven vasculitis in the absence of detectable MC (cases) were retrospectively compared with 48 HCV RNA+ patients with MC vasculitis (controls). Each case was matched with 4 controls for age and sex. the main epidemiological and virologic features were similar between cases and controls. No clinical difference was found, except for lower rates of arthralgias (33% vs 71%; p = 0.02) and purpura (50% vs 83%; p = 0.03) in cases. Cases showed higher mean serum C3 (1.17 ± 0.21 vs 0.93 ± 0.23 g/l; p = 0.01) and median C4 levels (0.25 vs 0.04 g/l; p < 0.001), lower median serum IgM levels (0.6 vs 1.9 g/l; p < 0.001), and lower rates of rheumatoid factor positivity (8% vs 82%; p < 0.001) than controls. The main histologic features were similar between cases and controls. Immunofluorescence analysis of skin biopsy from 1 case revealed perivascular deposits of C3 and IgA. After treatment, overall clinical response of vasculitis (75% vs 83%) and sustained virological response (40% vs 64%; p = 0.3) were similar between cases and controls, except for higher complete clinical response (42% vs 73%; p = 0.05) in controls. HCV-related systemic vasculitis may occur in the absence of detectable MC. Our findings suggest that such vasculitis probably results from immune complex-mediated mechanisms, and that the therapeutic management of such vasculitis should be similar to that of HCV-MC vasculitis.

  5. Genetic insights into the disease mechanisms of type II mixed cryoglobulinemia induced by hepatitis C virus.

    PubMed

    De Re, V; Caggiari, L; De Vita, S; Mazzaro, C; Lenzi, M; Galli, M; Monti, G; Ferri, C; Zignego, A L; Gabrielli, A; Sansonno, D; Dammacco, F; Libra, M; Sacchi, N; Talamini, R; Spina, M; Cannizzaro, R; Guidoboni, M; Dolcetti, R

    2007-09-01

    The ability of the immune system to distinguish between self and non-self is critical to the functioning of the immune response. A breakdown in these mechanisms can lead to the onset of autoimmune disease. Clinical and molecular data suggest that shared immunogenetic mechanisms lead to the autoimmune process. The most studied part of the autoimmune process is the human leukocyte antigen (HLA) region. Recently, progress has been made in narrowing down HLA cluster classifications based on structural and functional features of HLA alleles. Using this approach we have investigated 175 patients with hepatitis C virus (HCV)-induced type II cryoglobulinemia (MC), and compared them to a control group of 14,923 bone marrow donors. Additionally, we investigated the frequency of HLA homozygosity in the same groups of subjects. Our results provide evidence of a role for DR5 and DQ3 HLA class II clusters and a higher frequency of HLA homozygous leading to the clinical outcome of type II mixed cryoglobulinemic autoimmune disease. The DR5 cluster is characterized by a Glu in beta 9 and its polymorphism is connected with preferred anchors at beta 9 of the binding peptide, while the DQ3 cluster is characterized by Glu B86 and Leu B87, which allows the binding of large hydrophobic amino acids at p1 of the binding peptide. The mechanisms by which variations in HLA lead to autoimmunity remain unknown, although they are likely to be mediated by continuous presentation of HCV epitopes to T cells and a genetic background that limits the effective clearance of HCV. The results presented in this paper have increased our knowledge of the mechanism of autoimmune disease and B-cell lymphoproliferation during HCV infection. The work was performed in accordance with the principles of the 1983 Declaration of Helsinki. There is no conflict of interest.

  6. Somatic Hypermutations Confer Rheumatoid Factor Activity in Hepatitis C Virus–Associated Mixed Cryoglobulinemia

    PubMed Central

    Charles, Edgar D.; Orloff, Michael I. M.; Nishiuchi, Eiko; Marukian, Svetlana; Rice, Charles M.; Dustin, Lynn B.

    2014-01-01

    Objective Hepatitis C virus (HCV) is the most frequent cause of mixed cryoglobulinemia (MC), which is characterized by endothelial deposition of rheumatoid factor (RF)–containing immune complexes and end-organ vasculitis. MC is a lymphoproliferative disorder in which B cells express RF-like Ig, yet its precise antigenic stimulus is unknown. We have proposed that IgG–HCV immune complexes stimulate B cell expansion and somatic hypermutation (SHM)–induced affinity maturation in part via engagement of an RF-like B cell receptor. This study was undertaken to test the hypothesis that SHM augments RF activity. Methods RFs cloned from single B cells from 4 patients with HCV-associated MC (HCV-MC) were expressed as IgM, IgG, or IgG Fab. Selected Ig were reverted to germline. RF activity of somatically mutated Ig and germline-reverted Ig was determined by enzyme-linked immunosorbent assay. Results Ig with SHM had RF activity, with the preference for binding being highest for IgG1, followed by IgG2 and IgG4, and lowest for IgG3, where there was no detectable binding. In contrast, reverted germline IgG exhibited markedly diminished RF activity. Competition with 1 μg/ml of protein A abrogated RF activity, suggesting specificity for IgG Fc. Swapping of mutated heavy-chain pairs and light-chain pairs also abrogated RF activity, suggesting that context-specific pairing of appropriate IgH and Igκ, in addition to SHM, is necessary for RF activity. Conclusion SHM significantly contributes to RF activity in HCV-MC patients, suggesting that autoreactivity in these patients arises through antigen-dependent SHM, as opposed to nondeletion of autore-active germline Ig. PMID:23754128

  7. Treatment of hepatitis C virus-associated mixed cryoglobulinemia with direct-acting antiviral agents.

    PubMed

    Sise, Meghan E; Bloom, Allyson K; Wisocky, Jessica; Lin, Ming V; Gustafson, Jenna L; Lundquist, Andrew L; Steele, David; Thiim, Michael; Williams, Winfred W; Hashemi, Nikroo; Kim, Arthur Y; Thadhani, Ravi; Chung, Raymond T

    2016-02-01

    Hepatitis C virus (HCV) is the most common cause of mixed cryoglobulinemia syndrome (MCS). The efficacy and safety of all-oral direct-acting antiviral (DAA) therapy in HCV-associated MCS (HCV-MCS) is largely unknown. The authors studied case series of patients with HCV-MCS who were treated with sofosbuvir-based regimens and historical controls treated with pegylated interferon and ribavirin in a single health care network. HCV-MCS was defined by circulating cryoglobulin associated with systemic vasculitis symptoms. Renal involvement (n = 7) was established by kidney biopsy (n = 5) or by two or more of the following clinical findings: reduced kidney function, proteinuria, or hematuria with other causes excluded (n = 2). Twelve patients received DAA therapy between December 2013 and September 2014. Median age was 61 years, 58% were male, and 50% had cirrhosis. Median baseline serum creatinine was 0.97 mg/dL (range 0.7-2.47). Four patients received rituximab concurrent with DAA therapy. Sustained virological response rate at 12 weeks (SVR12) was 83% overall. Patients with glomerulonephritis who achieved SVR12 experienced an improvement in serum creatinine and a reduction in proteinuria. Cryoglobulin levels decreased in 89% of patients, with median percent decreasing from 1.5% to 0.5% and completely disappearing in four of nine cases who had cryoglobulins measured after treatment. Serious adverse events were infrequent (17%). In contrast, the historical cohort treated with pegylated interferon and ribavirin experienced only 10% SVR12, with 100% experiencing at least one adverse event and 50% experiencing premature discontinuation due to adverse events. SVR12 rates for sofosbuvir-based DAA regimens in HCV-MCS were 83%, significantly higher than historical controls treated with pegylated interferon and ribavirin; patients with glomerulonephritis experienced improvement in renal function, including those not concomitantly treated with immunosuppression. © 2015 by the

  8. Improvement in liver cirrhosis after treatment of HCV-related mixed cryoglobulinemia with rituximab.

    PubMed

    Petrarca, Antonio; Rigacci, Luigi; Monti, Monica; Giannini, Carlo; Bernardi, Franco; Caini, Patrizio; Colagrande, Stefano; Bosi, Alberto; Laffi, Giacomo; Zignego, Anna Linda

    2007-09-01

    Mixed cryoglobulinemia (MC) is the most strictly virus-related extrahepatic HCV disease. Antiviral therapy is considered the first therapeutic option; however, MC patients are frequently excluded from treatment due to contraindications. The effectiveness of B-cell depletion by anti-CD20 monoclonal antibody (rituximab) has recently been described, but the possibility of an immunodepression- related increase in viral replication and aminotransferase values limits its use in patients with advanced liver disease. Unfortunately, MC patients frequently also have cirrhosis. To our knowledge, no data are available regarding the effect of rituximab therapy in patients with decompensated cirrhosis. We report the successful treatment with rituximab (4 weekly infusions of 375 mg/m 2) of two patients (a 58-year-old man, and a 65-year-old woman) with HCV-related MC syndrome and decompensated liver cirrhosis. These patients underwent at least 6 months of post-treatment follow-up. In both cases a consistent improvement of MC syndrome was evident after treatment. In addition, improvement of liver protidosynthetic activity, increased prothrombin time, impressive reduction or disappearance of ascites and encephalopathy were also observed, in spite of some increase in viral titers or in ALT values. The Child-Pugh score improved from B8 to A6 and from Cll to B7, respectively. Pre- and post-treatment transjugular liver biopsies were available in 1 patient, showing disappearance of lymphocytic infiltration after treatment. These case reports show the effectiveness and safety of rituximab in patients with HCV-related MC and advanced cirrhosis, and strongly suggest that the depletion of CD20+ B-cells induced by rituximab treatment may be responsible for liver function improvement. The mechanisms involved are unknown. Interesting working hypotheses may implicate a role played by B-cell infiltrates in conditioning liver damage. The improvement of Kupffer cell function due to the cryocrit

  9. Assessment of liver stiffness in patients with HCV and mixed cryoglobulinemia undergoing rituximab treatment.

    PubMed

    Stasi, Cristina; Triboli, Elisa; Arena, Umberto; Urraro, Teresa; Petrarca, Antonio; Gragnani, Laura; Laffi, Giacomo; Zignego, Anna Linda

    2014-01-24

    Mixed cryoglobulinemia (MC) is a HCV-related lymphoproliferative disorder generally associated with advanced liver disease. Liver stiffness has been significantly correlated with histopathological stage of fibrosis. Moreover, it was influenced by necroinflammatory activity. Rituximab (RTX) is a chimeric anti-CD20 monoclonal antibody inducing transient B lymphocytes depletion that was shown to be useful and safe in the majority of HCV MC patients, leading also to improvement of cirrhotic syndrome. Aim of this study was to evaluate the modifications of liver stiffness following RTX treatment in HCV-related MC patients. Fourteen consecutive patients (10 F, 4 M; mean age 60.43 ± 43) with HCV-related chronic hepatitis (n = 10) or cirrhosis (n = 4) and MC, eligible for RTX treatment, were prospectively enrolled. Intravenous injection of 1 g of RTX was performed at day 0 and at day 15. Assessment of stiffness was carried out by Fibroscan (Echosens, Paris-France) at baseline, 15 days after the first infusion, and at month 1, 3 and 6 after therapy. MC symptoms significantly improved during the study, especially during the first 3 months. Liver stiffness observed 3 months after treatment was significantly reduced when compared with pre-treatment values (p = 0.01). This difference disappeared after 6 months of follow-up. Cytofluorimetric analysis showed a decrease of CD19+ peripheral blood cells, with the nadir at month 3 after therapy and B cell compartment reconstitution after 6 months. This study, for the first time showed that RTX-treatment in HCV-related MC induces a reduction of liver stiffness that is strictly associated with the B-cell depletion.

  10. Assessment of liver stiffness in patients with HCV and mixed cryoglobulinemia undergoing rituximab treatment

    PubMed Central

    2014-01-01

    Introduction Mixed cryoglobulinemia (MC) is a HCV-related lymphoproliferative disorder generally associated with advanced liver disease. Liver stiffness has been significantly correlated with histopathological stage of fibrosis. Moreover, it was influenced by necroinflammatory activity. Rituximab (RTX) is a chimeric anti-CD20 monoclonal antibody inducing transient B lymphocytes depletion that was shown to be useful and safe in the majority of HCV MC patients, leading also to improvement of cirrhotic syndrome. Aim of this study was to evaluate the modifications of liver stiffness following RTX treatment in HCV-related MC patients. Materials and methods Fourteen consecutive patients (10 F, 4 M; mean age 60.43 ± 43) with HCV-related chronic hepatitis (n = 10) or cirrhosis (n = 4) and MC, eligible for RTX treatment, were prospectively enrolled. Intravenous injection of 1 g of RTX was performed at day 0 and at day 15. Assessment of stiffness was carried out by Fibroscan® (Echosens, Paris-France) at baseline, 15 days after the first infusion, and at month 1, 3 and 6 after therapy. Results MC symptoms significantly improved during the study, especially during the first 3 months. Liver stiffness observed 3 months after treatment was significantly reduced when compared with pre-treatment values (p = 0.01). This difference disappeared after 6 months of follow-up. Cytofluorimetric analysis showed a decrease of CD19+ peripheral blood cells, with the nadir at month 3 after therapy and B cell compartment reconstitution after 6 months. Conclusion This study, for the first time showed that RTX-treatment in HCV-related MC induces a reduction of liver stiffness that is strictly associated with the B-cell depletion. PMID:24456582

  11. Cryoglobulinemia Vasculitis.

    PubMed

    Cacoub, Patrice; Comarmond, Cloe; Domont, Fanny; Savey, Léa; Saadoun, David

    2015-09-01

    Cryoglobulinemic vasculitis (CryoVas) is a small-vessel vasculitis involving mainly the skin, the joints, the peripheral nervous system, and the kidneys. Type I CryoVas is single monoclonal immunoglobulins related to an underlying B-cell lymphoproliferative disorder. Type II and III cryoglobulins, often referred to as mixed cryoglobulinemia, consist of polyclonal immunoglobulin (Ig)G with or without monoclonal IgM with rheumatoid factor activity. Hepatitis C virus (HCV) infection represents the main cause of mixed CryoVas. The 10-year survival rates are 63%, 65%, and 87% in HCV-positive mixed CryoVas, HCV-negative mixed CryoVas, and type I CryoVas patients, respectively. In HCV-positive patients, baseline poor prognostic factors include the presence of severe liver fibrosis, and central nervous system, kidney, and heart involvement. Treatment with antivirals is associated with a good prognosis, whereas use of immunosuppressants (including corticosteroids) is associated with a poor outcome. In HCV-negative patients, pulmonary and gastrointestinal involvement, renal insufficiency, and age > 65 years are independently associated with death. Increased risk of lymphoma also should be underlined. Treatment of type I CryoVas is that of the hemopathy; specific treatment also includes plasma exchange, corticosteroids, rituximab, and ilomedine. In HCV-CryoVas with mild-to-moderate disease, an optimal antiviral treatment should be given. For HCV-CryoVas with severe vasculitis (ie, worsening of renal function, mononeuritis multiplex, extensive skin disease, intestinal ischemia…) control of disease with rituximab, with or without plasmapheresis, is required before initiation of antiviral therapy. Other immunosuppressants should be given only in case of refractory forms of CryoVas, frequently associated with underlying B-cell lymphoma. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Role of microRNA profile modifications in hepatitis C virus-related mixed cryoglobulinemia.

    PubMed

    Fognani, Elisa; Giannini, Carlo; Piluso, Alessia; Gragnani, Laura; Monti, Monica; Caini, Patrizio; Ranieri, Jessica; Urraro, Teresa; Triboli, Elisa; Laffi, Giacomo; Zignego, Anna Linda

    2013-01-01

    Hepatitis C virus infection is closely related to lymphoproliferative disorders (LPDs), including mixed cryoglobulinemia (MC) and some lymphomas. Modification of the expression of specific microRNAs (miRNAs) has been associated with different autoimmune diseases and/or LPDs. No data exist about the modifications in miRNA expression in HCV-associated LPDs. The aim of this study was to analyze the expression levels of a panel of miRNAs previously associated with autoimmune/LPDs in a large population of HCV patients with and without MC or non-Hodgkin's lymphoma (NHL), to identify potential markers of evolution of HCV infection. PBMC expression of miR-Let-7d, miR-16, miR-21, miR-26b, miR-146a and miR-155 was evaluated by real-time PCR in 167 HCV patients (75 with MC [MC-HCV], 11 with HCV-associated NHL [NHL-HCV], 81 without LPD [HCV]) and in 35 healthy subjects (HS). A significant increase in miR-21 (p<0.001), miR-16 (p<0.01) and miR-155 (p<0.01) expression was detected in PBMCs from only NHL patients whereas a significant decrease in miR-26b was detected in both MC and NHL subjects (p<0.01) when compared to HS and HCV groups. A restoration of miR-26b levels was observed in the post-treatment PBMCs of 35 HCV-MC patients experiencing complete virological and clinical response following antiviral therapy. This study, for the first time, shows that specific microRNAs in PBMC from HCV patients who developed MC and/or NHL are modulated differently. The specific, reversible downregulation of miR-26b strongly suggests the key role it plays in the pathogenesis of HCV-related LPDs and its usefulness as a biomarker of the evolution of HCV infection to these disorders.

  13. Role of MicroRNA Profile Modifications in Hepatitis C Virus-Related Mixed Cryoglobulinemia

    PubMed Central

    Piluso, Alessia; Gragnani, Laura; Monti, Monica; Caini, Patrizio; Ranieri, Jessica; Urraro, Teresa; Triboli, Elisa; Laffi, Giacomo; Zignego, Anna Linda

    2013-01-01

    Hepatitis C virus infection is closely related to lymphoproliferative disorders (LPDs), including mixed cryoglobulinemia (MC) and some lymphomas. Modification of the expression of specific microRNAs (miRNAs) has been associated with different autoimmune diseases and/or LPDs. No data exist about the modifications in miRNA expression in HCV-associated LPDs. The aim of this study was to analyze the expression levels of a panel of miRNAs previously associated with autoimmune/LPDs in a large population of HCV patients with and without MC or non-Hodgkin’s lymphoma (NHL), to identify potential markers of evolution of HCV infection. PBMC expression of miR-Let-7d, miR-16, miR-21, miR-26b, miR-146a and miR-155 was evaluated by real-time PCR in 167 HCV patients (75 with MC [MC-HCV], 11 with HCV-associated NHL [NHL-HCV], 81 without LPD [HCV]) and in 35 healthy subjects (HS). A significant increase in miR-21 (p<0.001), miR-16 (p<0.01) and miR-155 (p<0.01) expression was detected in PBMCs from only NHL patients whereas a significant decrease in miR-26b was detected in both MC and NHL subjects (p<0.01) when compared to HS and HCV groups. A restoration of miR-26b levels was observed in the post-treatment PBMCs of 35 HCV-MC patients experiencing complete virological and clinical response following antiviral therapy. This study, for the first time, shows that specific microRNAs in PBMC from HCV patients who developed MC and/or NHL are modulated differently. The specific, reversible downregulation of miR-26b strongly suggests the key role it plays in the pathogenesis of HCV-related LPDs and its usefulness as a biomarker of the evolution of HCV infection to these disorders. PMID:23650540

  14. Serum levels of proinflammatory cytokines interleukin-1beta, interleukin-6, and tumor necrosis factor alpha in mixed cryoglobulinemia.

    PubMed

    Antonelli, Alessandro; Ferri, Clodoveo; Ferrari, Silvia Martina; Ghiri, Emiliano; Goglia, Fernando; Pampana, Alessandro; Bruschi, Fabrizio; Fallahi, Poupak

    2009-12-01

    No single previous study has evaluated serum levels of the proinflammatory cytokines interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor alpha (TNFalpha) in patients with hepatitis C virus-associated mixed cryoglobulinemia (HCV-MC). This study was undertaken to evaluate serum levels of these cytokines in patients with HCV-MC. Serum IL-1beta, IL-6, and TNFalpha were assayed in 43 patients with HCV-MC, in 43 sex- and age-matched patients with chronic HCV without cryoglobulinemia, and in 43 sex- and age-matched controls. HCV-MC patients showed significantly higher mean IL-1beta, IL-6, and TNFalpha levels than did the controls (P<0.01) or the HCV patients (P

  15. Cryoglobulinemia and hepatitis B markers in North African Jews with Raynaud's disease.

    PubMed

    Horowitz, J; Klein, M; Sukenik, S

    1986-08-01

    Mixed cryoglobulinemia was discovered in 11 of 20 patients with Raynaud's disease. Hepatitis B surface markers were found in 10 of these patients with cryoglobulinemia. All patients with cryoglobulinemia were female, and 10 were of northern African origin. This study indicates that, in a population with a high prevalence of hepatitis B infection, mixed cryoglobulinemia is an important etiologic factor in Raynaud's disease.

  16. Hepatitis C virus-associated mixed cryoglobulinemia. Clinical manifestations, histopathological changes, mechanisms of cryoprecipitation and options of treatment.

    PubMed

    Schott, P; Hartmann, H; Ramadori, G

    2001-10-01

    Chronic hepatitis C virus (HCV) infection is frequently associated with a variety of autoimmune phenomenons. Mixed cryoglobulinemia (MC) appears in up to 50% of chronic HCV-infected patients. Cryoglobulins consist of immunoglobulin complexes precipitating in vitro when cooled below body temperature. In most cases IgM with rheumatoid factor activity is found in cryoprecipitates which could lead to vasculitis induced by the deposition of immnuocomplexes in small vessels. This vasculitis is thought to cause clinical symptoms called Meltzer's triad. This triad is represented by purpura, arthralgia and weakness. One third of patients suffering from HCV-associated mixed cryoglobulinemia are developing typical symptoms during their course of disease. The striking association between HCV infection and MC has conduced to the hypothesis that HCV is of major importance in the production of MC with followed vasculitis. Both hepatrophism and lymphotrophism have been reported for the hepatitis C virus. Infection of B-cells by HCV could probably lead to a bcl-2 translocation and immunoglobulin gene rearrangement which results in clonal lymphoproliferation and in synthesis of monoclonal IgM with rheumatoid factor activity. These IgM form immunocomplexes with IgG in the cold, which are finally responsible for the described vasculitis. Histopathological changes of the liver are dominated by chronic HCV infection. The majority of times mild activity of hepatitis or mild fibrosis could be found. Nevertheless, cirrhosis is more often found in HCV-infected patients suffering from MC compared to patients without MC. Conventional treatment of MC is aimed to reduce circulating immune complexes by immunosupression and plasmapheresis. With the emerging concept of a viral pathogenesis the therapeutic approach has changed during the last decade. Interferon treatment of MC, particularly of HCV-associated MC is well established nowadays.

  17. Persistent cryoglobulinemic vasculitis following successful treatment of hepatitis C virus.

    PubMed

    Levine, James W; Gota, Carmen; Fessler, Barri J; Calabrese, Leonard H; Cooper, Sheldon M

    2005-06-01

    There is a well established link between type II mixed cryoglobulinemia (MC) and hepatitis C virus (HCV) infection, and HCV is believed to be the cause of cryoprotein formation and tissue deposition. Successful treatment of HCV infection has resulted in resolution of cryoglobulinemia and vasculitis. We describe 4 patients who had persistent MC and vasculitis despite successful eradication of HCV with antiviral therapy.

  18. Serum levels of immunoglobulin free light chains in patients with chronic hepatitis C presenting cryoglobulinemia.

    PubMed

    Oliveira, Isabela S; Cabral, Milena S; Jesus, Larissa S; Paraná, Raymundo; Atta, Ajax M; Sousa Atta, Maria Luiza B

    2014-01-01

    Hepatitis C virus (HCV) infects B-lymphocytes, provokes cellular dysfunction and causes lymphoproliferative diseases such as cryoglobulinemia and non-Hodgkin's B-cell lymphoma. In the present study, we investigated the serum levels of kappa and lambda free light chains (FLC) of immunoglobulins and the kappa/lambda FLC ratio in Brazilian patients with chronic HCV infection and cryoglobulinemia. We also analyzed the immunochemical composition of the cryoglobulins in these patients. Twenty-eight cryoglobulinemic HCV patients composed the target group, while 37 HCV patients without cryoglobulinemia were included as controls. The median levels of kappa and lambda FLC were higher in patients with cryoglobulinemia compared to controls (p=0.001 and p=0.003, respectively), but the kappa/lambda FLC ratio was similar in patients with and without cryoglobulinemia (p>0.05). The median FLC ratio was higher in HCV patients presenting with advanced fibrosis of the liver compared to HCV patients without fibrosis (p=0.004). Kappa and lambda FLC levels were strongly correlated with the IgA, IgG and IgM levels in the patients with cryoglobulinemia. In patients without cryoglobulinemia, the kappa FLC level was only correlated with the IgG level, whereas the lambda FLC were weakly correlated with the IgA, IgG and IgM levels. An immunochemical pattern of mixed cryoglobulins (MC), predominantly IgM, IgG, IgA and kappa light chain, was verified in these immune complexes. We concluded that HCV-infected patients presenting cryoglobulinemia have vigorous polyclonal B-lymphocyte activation due to chronic HCV infection and persistent immune stimulation.

  19. How I treat cryoglobulinemia.

    PubMed

    Muchtar, Eli; Magen, Hila; Gertz, Morie A

    2017-01-19

    Cryoglobulinemia is a distinct entity characterized by the presence of cryoglobulins in the serum. Cryoglobulins differ in their composition, which has an impact on the clinical presentation and the underlying disease that triggers cryoglobulin formation. Cryoglobulinemia is categorized into two main subgroups: type I, which is seen exclusively in clonal hematologic diseases, and type II/III, which is called mixed cryoglobulinemia and is seen in hepatitis C virus infection and systemic diseases such as B-cell lineage hematologic malignancies and connective tissue disorders. Clinical presentation is broad and varies between types but includes arthralgia, purpura, skin ulcers, glomerulonephritis, and peripheral neuropathy. Life-threatening manifestations can develop in a small proportion of patients. A full evaluation for the underlying cause is required, because each type requires a different kind of treatment, which should be tailored on the basis of disease severity, underlying disease, and prior therapies. Relapses can be frequent and can result in significant morbidity and cumulative organ impairment. We explore the spectrum of this heterogeneous disease by discussing the disease characteristics of 5 different patients.

  20. Hepatitis C virus infection, mixed cryoglobulinemia and BLyS upregulation: targeting the infectious trigger, the autoimmune response, or both?

    PubMed

    De Vita, Salvatore; Quartuccio, Luca; Fabris, Martina

    2008-12-01

    Mixed cryoglobulinemia syndrome (MCsn) is a systemic vasculitis prevalently mediated by immune complexes, i.e., mixed cryoglobulins, and characterized by non-neoplastic B-cell lymphoproliferation favouring the progression into frank B-cell non-Hodgkin lymphoma (NHL) in 5-10% of patients. The hepatitis C virus (HCV) infection is the etiologic agent in the large majority of MCsn cases and chronic antigenic stimulation by HCV is considered a key mechanism sustaining the proliferation of the RF-secreting B-cell clones. Besides chronic antigenic stimulation, cytokines and growth factors may also play a key role in sustaining B-cell overactivation. B-lymphocyte stimulator (BlyS) was recently described as a critical survival factor for B cells, promoting their activation and maturation. Abnormal production of BLyS alters immune tolerance by allowing the survival of autoreactive B cells, thus triggering autoimmune disorders. BLyS inhibits B-cell apoptosis, and B-cell apoptosis is implicated in the pathogenesis of MCsn, as well as of other autoimmune diseases. Both antiviral therapy and B- cell depletive therapy in MCsn may influence BlyS expression. Antiviral therapy, monotherapy against biologic targets downstream viral infection, or the combination of the two, should be optimized in the single patient and stage of the disease, based on disease pathobiology, efficacy and safety issues.

  1. Hepatitis C virus (HCV)-driven stimulation of subfamily-restricted natural IgM antibodies in mixed cryoglobulinemia.

    PubMed

    Perotti, Mario; Ghidoli, Nadia; Altara, Raffaele; Diotti, Roberta A; Clementi, Nicola; De Marco, Donata; Sassi, Monica; Clementi, Massimo; Burioni, Roberto; Mancini, Nicasio

    2008-06-01

    Hepatitis C virus (HCV) infection has been closely related to mixed cryoglobulinemia (MC). During HCV infection, cryoglobulins derive from the restricted expression of few germline genes as VH1-69, a subfamily highly represented in anti-HCV humoral response. Little is known about the self-reacting IgM component of the cryoprecipitate. In the present study, the IgM/K repertoire of an HCV-infected cryoglobulinemic patient was dissected by phage-display on well-characterized anti-HCV/E2 VH1-69-derived monoclonal IgG1/Kappa Fab fragments cloned from the same patient. All selected IgM clones were shown to react with the anti-HCV/E2 antibodies belonging to VH1-69 subfamily. More than 60% of selected clones showed a bias in VH gene usage, restricted to two VH subfamilies frequently described in autoimmune manifestations (VH3-23; VH3-21). Moreover, all selected clones showed an high similarity (>98.5%) to germline genes evidencing their natural origin. A possible hypothesis is that clones belonging to some subfamilies are naturally prone to react against other VH gene subfamilies, as VH 1-69. An antigen-driven stimulation of these subfamilies, and their overexpression as in HCV infection, could lead to a breaking of humoral homeostatic balance exposing the patients to the risk of developing autoimmune disorders.

  2. Predominance of type 1 (Th1) cytokine production in the liver of patients with HCV-associated mixed cryoglobulinemia vasculitis.

    PubMed

    Saadoun, David; Boyer, Olivier; Trébeden-Nègre, Hélène; Limal, Nicolas; Bon-Durand, Véronique; Andreu, Marita; Klatzmann, David; Piette, Jean Charles; Cacoub, Patrice

    2004-12-01

    Patients with hepatitis C virus (HCV) mixed cryoglobulinemia (MC) vasculitis have a higher mortality rate and more frequent incidence of cirrhosis than their cryoglobulin-negative counterparts. To compare the cytokine profile of liver-infiltrating T cells in HCV-infected patients with or without MC vasculitis. Hepatic biopsy specimens were obtained from HCV infected patients with and without MC vasculitis. Using intracellular staining and flow cytometry, we assessed the ability of freshly isolated liver T cells from these biopsies to produce IFN-gamma, TNF-alpha, IL-2, IL-4, and IL-10 in response to stimulation with PMA and ionomycin. HCV-MC vasculitis patients compared to HCV-MC negative controls have an enhanced hepatic T cells production of Th1-type cytokines [i.e. TNF-alpha(30.3 +/- 13% vs. 15.5 +/- 5%, P = 0.01), IL-2 (20.2 +/- 9% vs. 10 +/- 4%, P = 0.01) and IFN-gamma (22.2 +/- 11% vs. 9.4 +/- 4%, P = 0.008)], whereas IL-10, a representative Th2-type cytokine, was significantly lower (7.2 +/- 4% vs. 17 +/- 7%, P = 0.01). T cell from the liver of HCV-MC vasculitis patients display a significantly augmented liver Th1 profile compared to MC-negative controls. This enhanced production of type-1 cytokines may account for a more severe course of liver disease.

  3. [Atypical onset cryoglobulinemia: case report].

    PubMed

    Consolo, M; Amoroso, A; D'Amico, G; La Rosa, L; Vinci, M

    2012-01-01

    Cryoglobulinemia is a disease mediated by antibodies with the property to precipitate at temperatures below 37°C. It can be distinguished into a primitive form (also referred to as 'essential mixed cryoglobulinemia'), and a secondary form. In the essential mixed variant a key role is played by HCV infection. The pathogenesis of mixed cryoglobulinemia is mediated by immune complexes that are the most important cause of the vasculitic phenomena, typical of the disease. However, the severity of the clinical manifestations is not always related to the serum levels of cryoglobulins and immune complexes. In our case report, a 46-year old man came to our observation with asymmetric diffuse and invalidating arthralgies, with both substitutive and additive behaviour, located at pelvic girdle, inferior limbs and elbows, associated to skin lesion vascultis-like. The remote pathological anamnesis was characterized by a previous surgically treated non-Hodgkin lymphoma, and HCV infection. Despite several attempts were done, it was not possible to reveal cryoglobulins, nor reumatoid factor in the serum. Cryoglobulins resulted positive only after the third day of hospitalization, along with a new fever attack and a worsening of the vasculitic manifestations. In conclusion, this case demonstrated that cryoglobulinemia can occur with a totally atypical sequence of clinical manifestations which can be present before and in absence of the typical laboratory proofs.

  4. Clinical spectrum, treatment, and outcome of patients with type II mixed cryoglobulinemia without evidence of hepatitis C infection.

    PubMed

    Foessel, Laure; Besancenot, Jean-François; Blaison, Gilles; Magy-Bertrand, Nadine; Jaussaud, Roland; Etienne, Yves; Maurier, François; Audia, Sylvain; Martin, Thierry

    2011-04-01

    The clinical spectrum, etiologies, and best therapeutic approaches of type II mixed cryoglobulinemia (MC) not associated with hepatitis C virus (HCV) infection have been poorly described to date. We studied the clinical presentation and outcome of patients with type II MC with no evidence of HCV. This was a multicenter retrospective study on the clinical presentation and outcome of patients with type II MC without evidence of HCV infection. Only patients with symptomatic MC were included. Thirty-three patients were included (median followup 67.2 mo). Extensive investigations for associated diseases were performed at presentation. MC was related to an autoimmune disease in 14 patients, to a lymphoid malignancy in 4 patients, and to an infectious disease in 2 patients, while MC was classified as essential (primary) in 13. Essential MC tended to be more severe than secondary disease with, in particular, more frequent renal and peripheral nerve involvement. Most patients were treated with steroid with or without immunosuppressive agents, mainly cyclophosphamide. These treatments were unable to induce sustained remission. One patient was successfully treated with lenalidomide. Seven patients with nonmalignant MC were treated with rituximab; 2 had a sustained complete remission, 3 improved greatly but relapsed within 5 months, and 2 experienced a disease flare. An important proportion of non HCV-related type II MC remains essential. Efforts should be made to find other etiologies than HCV, because treatments with steroid and immunosuppressants are not satisfactory, especially in severe forms. In these situations anti-CD20 therapy may present the best option but should be used with caution. New agents such as lenalidomide remain to be evaluated.

  5. Treatment of Hepatitis C Virus-Associated Mixed Cryoglobulinemia with Sofosbuvir-Based Direct-Acting Antiviral Agents

    PubMed Central

    Sise, Meghan E.; Bloom, Allyson K.; Wisocky, Jessica; Lin, Ming V.; Gustafson, Jenna L.; Lundquist, Andrew L.; Steele, David; Thiim, Michael; Williams, Winfred W.; Hashemi, Nikroo; Kim, Arthur Y.; Thadhani, Ravi; Chung, Raymond T.

    2015-01-01

    Background Hepatitis C virus (HCV) is the most common cause of mixed cryoglobulinemia syndrome (MCS). The efficacy and safety of all-oral directly-acting antiviral (DAA) therapy in HCV-associated MCS (HCV-MCS) is largely unknown. Methods Case series of patients with HCV-MCS who were treated with sofosbuvir-based regimens and historical controls treated with pegylated interferon and ribavirin in a single healthcare network. HCV-MCS was defined by circulating cryoglobulin associated with systemic vasculitis symptoms. Renal involvement (N=7) was established by kidney biopsy (N=5) or by ≥ 2 of the following clinical findings: reduced kidney function, proteinuria, or hematuria with other causes excluded (N=2). Results Twelve patients received DAA therapy between December 2013 and September 2014. Median age was 61 years, 58% male, 50% had cirrhosis. Median baseline serum creatinine was 0.97 mg/dL (range 0.7 – 2.47 mg/dL.) Four patients received Rituximab concurrent with DAA therapy. Sustained virological response rate at twelve weeks (SVR12) was 83% overall. Patients with glomerulonephritis who achieved SVR12 experienced an improvement in serum creatinine and reduction in proteinuria. Cryoglobulin levels decreased in 89% of patients, with median percent decreasing from 1.5% to 0.5%, and completely disappearing in 4 of 9 cases who had cryoglobulins measured after treatment. Serious adverse events were infrequent (17%). In contrast, the historical cohort treated with pegylated interferon and ribavirin experienced only 10% SVR12 rate with 100% experiencing at least one adverse event, and 50% experiencing premature discontinuation due to adverse events. Conclusion SVR12 rates for sofosbuvir-based direct acting antiviral regimens in HCV-MCS were 83%, significantly higher than historical controls treated with pegylated interferon and ribavirin. Patients with glomerulonephritis experienced improvement in renal function, including those not concomitantly treated with

  6. Safety and efficacy of rituximab in patients with hepatitis C virus-related mixed cryoglobulinemia and severe liver disease.

    PubMed

    Petrarca, Antonio; Rigacci, Luigi; Caini, Patrizio; Colagrande, Stefano; Romagnoli, Paolo; Vizzutti, Francesco; Arena, Umberto; Giannini, Carlo; Monti, Monica; Montalto, Paolo; Matucci-Cerinic, Marco; Bosi, Alberto; Laffi, Giacomo; Zignego, Anna Linda

    2010-07-22

    The effectiveness of rituximab in hepatitis C virus (HCV)-related mixed cryoglobulinemia (MC) has been shown. However, the risk of an increase in viral replication limits its use in cirrhosis, a condition frequently observed in patients with MC. In this prospective study, 19 HCV-positive patients with MC and advanced liver disease, who were excluded from antiviral therapy, were treated with rituximab and followed for 6 months. MC symptoms included purpura, arthralgias, weakness, sensory-motor polyneuropathy, nephropathy, and leg ulcers. Liver cirrhosis was observed in 15 of 19 patients, with ascitic decompensation in 6 cases. A consistent improvement in MC syndrome was evident at the end-of-treatment (EOT) and end-of-follow-up (EOF-U). Variable modifications in both mean viral titers and alanine aminotransferase values were observed at admission, EOT, third month of follow-up, and EOF-U (2.62 x 10(6), 4.28 x 10(6), 4.82 x 10(6), and 2.02 x 10(6) IU/mL and 63.6, 49.1, 56.6, and 51.4 IU/L, respectively). Improvement in liver protidosynthetic activity and ascites degree was observed at EOT and EOF-U, especially in more advanced cases. This study shows the effectiveness and safety of rituximab in MC syndrome with advanced liver disease. Moreover, the depletion of CD20(+) B cells was also followed by cirrhosis syndrome improvement despite the possibility of transient increases of viremia titers.

  7. PegIFNα/ribavirin/protease inhibitor combination in severe hepatitis C virus-associated mixed cryoglobulinemia vasculitis.

    PubMed

    Saadoun, David; Resche Rigon, Matthieu; Pol, Stanislas; Thibault, Vincent; Blanc, François; Pialoux, Gilles; Karras, Alexandre; Bazin-Kara, Dorothée; Cazorla, Cécile; Vittecoq, Daniel; Musset, Lucile; Peltier, Julie; Decaux, Olivier; Ziza, Jean-Marc; Lambotte, Olivier; Cacoub, Patrice

    2015-01-01

    The aim of this study was to analyse the safety and efficacy of the PegIFNα/ribavirin/protease inhibitor combination in severe and/or refractory hepatitis C virus (HCV)-mixed cryoglobulinemia (MC) vasculitis. This prospective cohort study included 30 patients (median age 59 years [53-66] and 57% of women) with HCV-MC vasculitis. PegIFNα/ribavirin (for 48 weeks) was associated with telaprevir (375 mg three times daily, for 12 weeks, [n = 17]) or boceprevir (800 mg three times daily, for 44 weeks, (n = 13]). Twenty three patients (76.7%) were non-responders to previous antiviral therapy. At week 72, twenty patients (66.7%) were complete clinical and sustained virological responders. The cryoglobulin level decreased from 0.45 to 0 g/L (p<0.0001) and the C4 level increased from 0.09 to 0.14 g/L (p = 0.017). Complete clinical responders had a higher frequency of purpura (16/20 [80%] vs. 4/10 [40%], p = 0.045), and a trend towards lower frequency of neuropathy (9/20 (45%) vs. 8/10 [80%], p = 0.12) compared with partial responders. Serious adverse events occurred in 14 patients (46.6%) during the 72 weeks of follow-up. Twenty eight patients (93.3%) received erythropoietin, 14 (46.6%) had red blood cell transfusion and 2 (6.6%) received granulocyte stimulating agent. The baseline factors associated with serious adverse events included liver fibrosis (p = 0.045) and a low platelet count (p = 0.021). The PegIFNα/ribavirin/protease inhibitor combination is highly effective in severe and/or refractory HCV-MC at the cost of frequent side effects. Baseline platelet count and liver fibrosis are useful in guiding treatment decisions. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  8. Increased T-cell sinusoidal lymphocytosis in liver biopsies in patients with chronic hepatitis C and mixed cryoglobulinemia.

    PubMed

    Carmack, Susanne; Taddei, Tamar; Robert, Marie E; Mistry, Pramod; Jain, Dhanpat

    2008-03-01

    Mixed cryoglobulinemia (MC) has a strong association with hepatitis C virus (HCV) infection and is associated with a higher degree of fibrosis and poor response to therapy. Currently, there are no known histological findings on liver biopsy that correlate with the presence of MC in HCV-infected patients, although we have occasionally noted prominent sinusoidal lymphocytosis in MC patients. The goal of this study is to determine whether sinusoidal lymphocytosis is a histological marker of MC in liver biopsies from patients with chronic hepatitis C. The liver clinic database at our institution was searched for chronic hepatitis C patients with MC who underwent liver biopsy during 1999-2005. Ten such cases were identified and were included in the study. Ten chronic hepatitis C MC-negative cases were matched for age and stage of fibrosis to serve as controls. Histological features (sinusoidal lymphocytes, inflammatory activity, acidophil bodies, and fibrosis stage) were evaluated in each biopsy. Clinical and laboratory data (serum protein electrophoresis, liver enzymes, hepatitis C viral load, treatment status, comorbidities, etc.) were also recorded. Formalin-fixed, paraffin-embedded sections were submitted for immunohistochemical analysis using antibodies against CD3, CD20, CD4, CD8, and CD68. Sinusoidal lymphocytes were counted in 5 hpf (40x) on hematoxylin and eosin (H&E) stain, and on CD3 and CD20 immunostains. The number of CD68+ Kupffer cells was also counted in a similar fashion. In the MC-positive versus MC-negative cases, mean fibrosis stage (2.4 vs. 2.4), inflammatory grade (1.7 vs. 2.1), lymphocyte count (359 vs. 128/5 hpf), and Kupffer cell count (239 vs. 220/5 HPF) were assessed. There was a significant increase in sinusoidal T-cell lymphocytes (P < 0.05) in MC-positive cases as compared to MC-negative cases. Nearly all sinusoidal lymphocytes were CD8-positive cells in both groups. Other histological parameters did not differ in the two groups. MC

  9. Interferon mono-therapy for symptomatic HCV-associated mixed cryoglobulinemia : meta-analysis of clinical studies.

    PubMed

    Fabrizi, Fabrizio; Dixit, Vivek; Messa, Piergiorgio

    2013-12-01

    Mixed cryoglobulinemia (MC) is an important complication of hepatitis C virus (HCV) infection. Antiviral therapy is now an important approach for symptomatic HCV-MC; some information exists on IFN mono-therapy for symptomatic HCV-MC in the non-transplant setting, but its efficacy is still unclear. We evaluated efficacy and safety of mono-therapy with standard or pegylated interferon (IFN) for symptomatic HCV-associated MC in non-immunosuppressed individuals by performing a systematic review of the literature with a meta-analysis of clinical studies. We used the random-effects model of DerSimonian and Laird with heterogeneity and sensitivity analyses. The primary outcome was sustained viral response (SVR, as a measure of efficacy), and the secondary outcome was the drop-out rate due to side-effects (as a measure of tolerability). We identified eleven clinical studies (n = 235 unique patients) ; the rate of baseline kidney involvement ranged between 11% and 74%. The summary estimate of frequency of sustained viral response was 0.15 with a 95% Confidence Interval (CI) of 0.08; 0.22 (random-effects model). Significant heterogeneity occurred (P= 0.001; Chi= 28.9%). Stratified analysis did not meaningfully change the results. The frequency of patients stopping antiviral agents was 3.4% ; most patients experienced minor side effects which did not require interruption of therapy. Baseline cirrhosis (P <0.04), kidney involvement (P <0.07), and arthralgias (P <0.04) showed negative impact on viral response. We found an excellent relationship between viral and clinical response [weighted K = 0.72 (95% CI, 0.54; 0.89)], by an evaluation at individual level on a subset of reports (n = 65 unique patients). This meta-analysis of clinical studies shows that antiviral therapy with standard or pegylated IFN alone for symptomatic MC associated with HCV gives satisfactory response in a minority of patients only. Clinical trials based on combination therapy (pegylated interferon plus

  10. Increased CXCL9 serum levels in hepatitis C-related mixed cryoglobulinemia, with autoimmune thyroiditis, associated with high levels of CXCL10.

    PubMed

    Antonelli, Alessandro; Fallahi, Poupak; Ferrari, Silvia Martina; Colaci, Michele; Giuggioli, Dilia; Saraceno, Giovanna; Benvenga, Salvatore; Ferri, Clodoveo

    2013-12-01

    Until now, no study has evaluated CXCL9 in hepatitis C virus (HCV) infection-related mixed cryoglobulinemia (MC) patients in presence/absence of autoimmune thyroiditis (AT). Serum CXCL9 and CXCL10 have been measured in 60 patients with MC (MCo), in 35 patients with MC and AT (MC-AT), in sex and age-matched controls: 60 healthy (Control 1); 35 patients with AT without cryoglobulinemia (Control 2). CXCL9 and CXCL10 were higher in MC-AT patients than Control 2 (P<0.0001) and MCo (P=0.01), in MCo than Control 1 (P<0.0001), and in Control 2 than Control 1 (P<0.001). By defining a high CXCL9 level as a value>2 SD above the mean value of the Control 1 (>122 pg/mL), 5% of Control 1, 34% of Control 2, 91% of MCo, and 97% of MC+AT had high CXCL9 (P<0.0001, chi-square). By simple regression analysis CXCL9 and CXCL10 were related to each other in MCo (r=0.426, P=0.001) and in MC-AT (r=0.375, P=0.001). We first demonstrate high serum levels of CXCL9 in cryoglobulinemic patients, especially with AT. Further, a strong association between serum CXCL9 and CXCL10 has been observed in patients with MC in presence/absence of AT.

  11. HCV-related immunocytoma and type II mixed cryoglobulinemia-associated autoantigens.

    PubMed

    Simula, Maria Paola; Caggiari, Laura; Gloghini, Annunziata; De Re, Valli

    2007-09-01

    Hepatitis C virus (HCV) is a hepatotropic virus causing hepatocellular damage and chronic liver inflammation that progressively can lead to cirrhosis and hepatocellular carcinoma (HCC). HCV is also lymphotropic, as demonstrated by its capacity to replicate in lymphocytes, by the recurrent detection of organ- and non-organ-specific autoantibodies in HCV-infected patients, and by the strong association found between HCV infection and type II mixed cryoglobulinemic syndrome (MC-II). Moreover, accumulating data ascribe an etiopathogenetic role in the development of B cell non-Hodgkin's lymphomas (NHL) to HCV. All these findings account for the profound effect of HCV infection in the host's immune system. The unique virus-host interactions that culminate in the generation and sustained production of autoantibodies and cryoglobulins have not been delineated. It appears that chronic antigenic stimulation could cause the emergence of specific B cell clones that produce cryoglobulins; moreover, B cell activation and/or deregulation could originate as a result of HCV binding to CD81 tetraspanin or as a consequence of its ability to replicate in B cells. In a previous study we demonstrated that, in MC-II HCV-positive patients, cryoprecipitated monoclonal IgMs, and B cell receptors (BCR) of overexpanded B cell clones share the same combinatory region. Moreover, these IgMs were reactive against both the Fc region of human IgG and the HCV-NS3 antigen. NS3 and Fc epitopes have been idengified by epitope excision approach. One of the idengified NS3 epitopes has been used to immunize a mouse and the monoclonal antibody obtained showed the same cross-reactivity as patients' IgMs. The characterization of antigenic specificity of this antibody may be useful to idengify antigens that can stimulate B cell proliferation in HCV-infected individuals.

  12. HCV Proteins and Immunoglobulin Variable Gene (IgV) Subfamilies in HCV-Induced Type II Mixed Cryoglobulinemia: A Concurrent Pathogenetic Role

    PubMed Central

    Sautto, Giuseppe; Mancini, Nicasio; Solforosi, Laura; Diotti, Roberta A.; Clementi, Massimo; Burioni, Roberto

    2012-01-01

    The association between hepatitis C virus (HCV) infection and type II mixed cryoglobulinemia (MCII) is well established, but the role played by distinct HCV proteins and by specific components of the anti-HCV humoral immune response remains to be clearly defined. It is widely accepted that HCV drives the expansion of few B-cell clones expressing a restricted pool of selected immunoglobulin variable (IgV) gene subfamilies frequently endowed with rheumatoid factor (RF) activity. Moreover, the same IgV subfamilies are frequently observed in HCV-transformed malignant B-cell clones occasionally complicating MCII. In this paper, we analyze both the humoral and viral counterparts at the basis of cryoglobulins production in HCV-induced MCII, with particular attention reserved to the single IgV subfamilies most frequently involved. PMID:22690241

  13. Hepatitis C Virus-Induced Cryoglobulinemia

    PubMed Central

    Charles MD, Edgar D.; Dustin, Lynn B.

    2009-01-01

    In this review we discuss the clinical manifestations, pathogenesis, and treatment of hepatitis C virus (HCV)-related cryoglobulinemia. HCV is a major cause of liver-related morbidity and is increasingly recognized as an instigator of B cell lymphoproliferative disorders such as mixed cryoglobulinemia and non-Hodgkin lymphoma. Cryoglobulinemia is characterized by the clonal expansion of rheumatoid factor-expressing B cells in the liver, lymph nodes and peripheral blood, resulting in the presence of cryoglobulins in the circulation. Cryoglobulins are cold-insoluble immune complexes containing rheumatoid factor, polyclonal IgG, and HCV RNA that precipitate and deposit on vascular endothelium, effecting a vasculitis in organs such as the skin, kidneys, and peripheral nerves. A subset of patients develops a low-grade lymphoma comprised of B cells that are immunophenotypically similar to the expanded B cells seen in cryoglobulinemia. HCV-related B cell lymphoproliferative disorders likely comprise a spectrum of disease, ranging from asymptomatic clonal B cell expansions to pathogenic cryoglobulinemia and lymphoma. It is unclear how B cells become dysregulated during the course of chronic HCV infection, and continued patient-centered research is necessary to elucidate the pathogenesis of HCV-related B cell dysregulation. PMID:19606079

  14. Cryoglobulinemia and renal disease.

    PubMed

    Alpers, Charles E; Smith, Kelly D

    2008-05-01

    Cryoglobulinemia occurs in a variety of clinical settings including lymphoproliferative disorders, infection and autoimmune disease. The worldwide pandemic of hepatitis C virus infection has resulted in a significant increase in its extrahepatic complications including cryoglobulinemia and renal disease. Here we review the types of cryoglobulins, mechanisms of cryoglobulin formation, links between hepatitis C virus and renal disease, and current approaches to therapy. The prevalence of cryoglobulinemia in hepatitis C virus-infected individuals is surprisingly large and may be found in more than 50% of some infected subpopulations. Most of these patients will not have overt renal disease, but there is a population of unknown size of patients with subclinical glomerular disease that has the potential to become clinically significant. In cases of hepatitis C virus-associated cryoglobulinemia, treatment remains focused on eradication of viremia, but interventions directed at B lymphocytes are increasingly utilized. The mechanisms of cryoglobulin formation and renal injury remain largely obscure, but recent evidence implicates the innate immune system in the initiation of disease. The most common renal injury associated with hepatitis C virus infection, in patients both with and without evidence of cryoglobulinemia, is membranoproliferative glomerulonephritis. There has been increasing focus on defining the mechanisms that link these processes and the evolution of renal injury in all clinical settings of cryoglobulinemia.

  15. Clinical, biochemical, and histological changes in hepatitis C virus infection-associated cryoglobulinemia.

    PubMed

    Fayyazi, A; Schott, P; Hartmann, H; Mihm, S; Middel, P; Ramadori, G; Radzun, H J

    1997-10-01

    The most common extrahepatic manifestation of HCV infection is mixed cryoglobulinemia (MC). 62 unselected patients with chronic HCV infection were prospectively evaluated for the presence of cryoglobulinemia and associated clinical and biochemical parameters. Furthermore, a putative relationship between the HCV genotypes and cryoglobulinemia was tested. Histological features typical for HCV infection were comparatively analyzed in cases with and without cryoglobulinemia. Whether an intrahepatic Th2-response is responsible for the strong antibody production causing cryoglobulinemia was also examined. Cryoglobulins were detected in sera of 30 patients (approximately equal to 48%). Patients with cryoglobulinemia were on the average elder, showed an apparent longer duration of infection, and suffered more frequently from arthralgia, accompanied by a significant increase of total serum IgM concentration and rheumatoid factor activity. The HCV genotype distribution among patients with cryoglobulinemia was not different from that found in patients without cryoglobulinemia. In cases with cryoglobulinemia, an increased activity of chronic hepatitis and a higher grade of liver fibrosis was noted. The prevalence of HCV-typical histological lesions among all patients were: Portal lymphocytic aggregates (40%), bile duct damage (35%), steatosis (47%), and intracellular acidophilic bodies (29%). A significant correlation, however, could not be found between cryoglobulinemia and the presence of HCV-typical histological lesions. An intrahepatic Th2-response causing an increased antibody production could not be observed in cases with cryoglobulinemia.

  16. Cryoglobulinemia vasculitis: an update.

    PubMed

    Terrier, Benjamin; Cacoub, Patrice

    2013-01-01

    Cryoglobulinemia vasculitis (CryoVas) is a small-vessel vasculitis associated with chronic infections [in particular hepatitis C virus, (HCV)], autoimmune disorders and B-cell lymphoproliferative disorders. The most recent studies on its diagnosis, prognosis and therapeutic management are reviewed here. Large series of patients with HCV-positive and negative mixed CryoVas and patients with monoclonal type I CryoVas have described the presentation and the prognosis of patients with CryoVas in the era of HCV screening. European experts in the field of CryoVas developed new classification criteria for its diagnosis. Finally, French, Italian and North American clinical studies demonstrated that rituximab-based regimens were highly effective in comparison with corticosteroids alone or other immunosuppressive agents-based therapy. However, rituximab seems to be associated with an increased risk of severe infections in a subset of patients. Recent studies identified prognostic factors of survival and demonstrated that rituximab is highly effective but remains associated with severe infections in a subset of patients. These results could support individual therapeutic stratification according to the clinical pattern and associated comorbidities.

  17. Vascular cell adhesion molecule-1 (VCAM-1) plays a central role in the pathogenesis of severe forms of vasculitis due to hepatitis C-associated mixed cryoglobulinemia.

    PubMed

    Kaplanski, Gilles; Maisonobe, Thierry; Marin, Valérie; Grès, Sandra; Robitail, Stéphane; Farnarier, Catherine; Harlé, Jean-Robert; Piette, Jean-Charles; Cacoub, Patrice

    2005-03-01

    To better characterize the molecules involved in leukocyte tissue infiltration during hepatitis C-mixed cryoglobulinemia (HCV-MC)-associated vasculitis. The involvement of ELAM, ICAM-1 and VCAM-1 was evaluated in 36 patients with HCV-MC vasculitis using three different approaches: concentrations of soluble forms by specific ELISA, tissue expression by immunohistochemistry on patients nerve biopsies, endothelial expression by FACS analysis, on cells activated in vitro by cryoprecipitates purified from HCV-MC patients. Concentrations of sVCAM-1 were significantly elevated in the serum of HCV-MC patients compared to HCV patients without MC, the highest concentrations being found in severe vasculitis. VCAM-1 expression was detected on blood vessels from nerve biopsies performed in patients with severe vasculitis. When added to endothelial cells in vitro, HCV-MC patients cryoprecipitate induced VCAM-1 but also ELAM and ICAM-1 expression possibly through a mechanism due to the C1q complement fraction interaction with endothelial cells, since C1q was consistently present in the cryoprecipitates. VCAM-1 is mainly involved in the pathogenesis of HCV-MC-associated severe vasculitis and may be a potential interesting therapeutic target.

  18. Hepatic and Mesenteric Vasculitis as Presenting Manifestation of Mixed Cryoglobulinemia Related to Chronic Hepatitis C Virus Infection in a Female Patient.

    PubMed

    Calle Toro, Juan S; Davalos, Diana M; Charry, Jose D; Arrunategi, Ana M; Tobon, Gabriel

    2016-06-01

    Approximately 80% of patients with hepatitis C virus infection develop chronic liver disease as cirrhosis, and 40% develop autoimmune complications as mixed cryoglobulinemia (MC). Gastrointestinal involvement in MC is rare, and even more so is hepatic involvement. We report a case of an 87-year-old woman with a 10-year history of blood transfusion-acquired hepatitis C virus infection, without treatment. She consulted the emergency department for diffuse abdominal pain, associated with vomiting. After 2 weeks of hospitalization in the intensive care unit, a diagnosis of MC was made; cirrhosis and secondary mesenteric and hepatic vasculitis were confirmed by a diagnostic laparoscopy. Unfortunately the condition of the patient worsened with sepsis and resulted in death in the fourth week from admission. This case highlights the importance of having in mind gastrointestinal tract vasculitis as a medical cause of abdominal pain in patients with chronic hepatitis C virus infection and using data laboratory tests, images, and histopathologic studies to aid with the diagnosis.

  19. Correlation of clinical and virologic responses to antiviral treatment and regulatory T cell evolution in patients with hepatitis C virus-induced mixed cryoglobulinemia vasculitis.

    PubMed

    Landau, Dan-Avi; Rosenzwajg, Michelle; Saadoun, David; Trébeden-Negre, Hélène; Klatzmann, David; Cacoub, Patrice

    2008-09-01

    Mixed cryoglobulinemia (MC) vasculitis is an autoimmune disorder associated with chronic hepatitis C virus (HCV) infection. We previously reported that MC vasculitis is associated with a quantitative defect of peripheral blood regulatory T cells. The aim of this study was to prospectively evaluate the evolution of this defect during the course of antiviral treatment. Treg cell frequencies and numbers were analyzed in 131 patients with chronic HCV infection (including 66 with MC vasculitis) and 20 healthy volunteer donors. Measurements were taken before, during, and after treatment with PEGylated interferon alfa-2b plus ribavirin. At baseline, patients with MC vasculitis had a significantly lower frequency and number of Treg cells than did patients without MC vasculitis. Complete remission of MC vasculitis following antiviral treatment was associated with a significant increase in Treg cell levels compared with baseline. In contrast, Treg cell levels in nonresponders or partial responders, which did not differ from those in complete responders at baseline, remained unchanged over the course of the study. The strong positive correlation between clinical responses and Treg cell levels provides further support for the central role of Treg cells in the pathogenesis of HCV-induced MC vasculitis and emphasizes the dual role of Treg cells in chronic HCV infection: while Treg cells may hinder viral elimination, they also limit autoimmune injury.

  20. Membranoproliferative glomerulonephritis and mixed cryoglobulinemia after hepatitis C virus infection secondary to glomerular NS3 viral antigen deposits.

    PubMed

    Bataille, Stanislas; Kaplanski, Gilles; Boucraut, José; Halfon, Philippe; Camus, Claire; Daniel, Laurent; Burtey, Stéphane; Berland, Yvon; Dussol, Bertrand

    2012-01-01

    We report on 3 cases of membranoproliferative glomerulonephritis associated with mixed cryoglobulin in patients with hepatitis C virus (HCV) antibodies but a negative blood viral load. These cases explore the pathogenesis of the renal disease. We searched for occult HCV infection in peripheral blood mononuclear cells, cryoprecipitate, bone marrow cells, and glomeruli using ultrasensitive PCR assays and immunohistochemistry. We also looked for infraclinical B cell lymphoma by computed tomodensitometry, bone marrow aspiration and biopsy, and lymphocyte typing. By PCR assays, we did not evidence occult hepatitis C infection in peripheral blood mononuclear cells, bone marrow cells, or cryoprecipitates. In the only patient with available kidney specimen, we evidenced HCV-NS3 antigen in glomeruli. HCV-associated lymphoma was excluded, but mild polyclonal B lymphocytosis was present in the 3 patients. Remission occurred spontaneously in 1 patient, and in another patient it occurred after rituximab treatment. The third patient was lost to follow-up. In patients with hepatitis C-negative viral load, membranoproliferative glomerulonephritis could be induced by the persistence of HCV antigen in the kidney but not in hematopoietic cells. Nonlymphomatous B cell proliferation may also be induced by chronic viral stimulation. Copyright © 2012 S. Karger AG, Basel.

  1. [Cryoglobulinemia and hepatitis C virus infection].

    PubMed

    Garini, G; Catellani, W; Manganelli, P; Buzio, C

    2001-01-01

    The demonstration of the high prevalence of HCV infection (HCV) in patients with MC has changed the clinico-biologic scenario of MC, supporting its subdivision into two groups: MC HCV- and MC HCV+. The former, which is predominantly a polyclonal cryoglobulinemia, should be regarded as an epiphenomenon of the immune system activation in the course of a variety of chronic infections or autoimmune disorders; the latter, which is a oligo- or monoclonal cryoglobulinemia, referred in the past as "essential mixed cryoglobulinemia", might be expression of an indolent B cell proliferation stimulated by HCV in an antigen-driven mechanism. The association of HCV infection with MC may have a pathogenetic an therapeutic significance. There are a number of reports demonstrating the beneficial effects of alpha-interferon (alpha-IFN) in about a half of patients with chronic HCV and MC. However, after the end of alpha-IFN therapy a recurrence of viremia and cryoglobulinemia is frequently observed and less than 25% of treated patients achieve long term remissions. To improve the sustained response rate, prolonged courses of alpha-IFN monotherapy or a combination of alpha-IFN and ribavirin should be considered. New agents with specific antiviral activity against HCV will probably further improve therapeutic options.

  2. Generalized livedo reticularis associated with monoclonal cryoglobulinemia and multiple myeloma.

    PubMed

    Requena, Luis; Kutzner, Heinz; Angulo, Jorge; Renedo, Guadalupe

    2007-02-01

    Cryoglobulins are detected in a wide variety of diseases, including malignancies, infections and systemic autoimmune diseases. Classically, monoclonal cryoglobulinemia is associated with hematologic malignancies, whereas mixed cryoglobulinemias are reported in association with hepatitis C virus infections or autoimmune diseases. We present a patient with generalized livedo reticularis as the first manifestation of monoclonal cryoglobulinemia and multiple myeloma. Histopathology demonstrated that nearly all small blood vessels of the upper and deep dermis, as well as the capillaries of the fat lobule, were filled with homogeneous, eosinophilic material that corresponded to monoclonal cryoglobulin deposits within the vascular lumina. Our case of livedo reticularis associated with monoclonal cryoglobulinemia and multiple myeloma was exceptional, because the mottled cyanotic discoloration of the skin with a reticular pattern was generalized, covering most of the skin surface. We have not found previous report of similar cases. Therefore, we recommend that dermatologists be made aware of the significance of this diagnosis.

  3. [A patient with cryoglobulinemia and hepatitis C].

    PubMed

    Wallnöfer de Jong, A G; Conzelmann, M; Steiger, U

    1997-10-22

    We describe a 73-year-old woman who presented with purpura, recurrent ulcerations of both lower limbs as well as worsening of her condition. Laboratory tests revealed a mixed cryoglobulinemia (type-II). Two years after diagnosis, an amputation of the right femur had been performed due to extensive necrotizing ulcerations. Further complications such as membranoproliferative glomerulonephritis, cirrhosis of the liver with portal hypertension and ultimately, hepatocellular carcinoma developed. A chronic hepatitis C infection was diagnosed rather late, mainly because of the false negative results of the first generation EIA. This case report illustrates the various complications-hepatic and extrahepatic-of chronic hepatitis C infection. The pathogenesis of mixed cryoglobulinemia remains unclear. However, a current literature review suggests a strong association with chronic hepatitic C. Diagnosis, clinical features and course of hepatitis C infection are discussed.

  4. Clonal B cells in patients with hepatitis C virus–associated mixed cryoglobulinemia contain an expanded anergic CD21low B-cell subset

    PubMed Central

    Charles, Edgar D.; Brunetti, Claudia; Marukian, Svetlana; Ritola, Kimberly D.; Talal, Andrew H.; Marks, Kristen; Jacobson, Ira M.; Rice, Charles M.

    2011-01-01

    Hepatitis C virus (HCV) is associated with the B-cell lymphoproliferative disorders mixed cryoglobulinemia (MC) and non-Hodgkin lymphoma. We have previously reported that HCV+MC+ patients have clonal expansions of hypermutated, rheumatoid factor–bearing marginal zone-like IgM+CD27+ peripheral B cells using the VH1-69 gene. Here we coupled transcriptional profiling with immunophenotypic and functional studies to ascertain these cells' role in MC pathogenesis. Despite their fundamental role in MC disease, these B cells have overall transcriptional features of anergy and apoptosis instead of neoplastic transformation. Highly up-regulated genes include SOX5, CD11C, galectin-1, and FGR, similar to a previously described FCRL4+ memory B-cell subset and to an “exhausted,” anergic CD21low memory B-cell subset in HIV+ patients. Moreover, HCV+MC+ patients' clonal peripheral B cells are enriched with CD21low, CD11c+, FCRL4high, IL-4Rlow memory B cells. In contrast to the functional, rheumatoid factor–secreting CD27+CD21high subset, the CD27+CD21low subpopulation exhibits decreased calcium mobilization and does not efficiently differentiate into rheumatoid factor–secreting plasmablasts, suggesting that a large proportion of HCV+MC+ patients' clonally expanded peripheral B cells is prone to anergy and/or apoptosis. Down-regulation of multiple activation pathways may represent a homeostatic mechanism attenuating otherwise uncontrolled stimulation of circulating HCV-containing immune complexes. This study was registered at www.clinicaltrials.gov as #NCT00435201. PMID:21421840

  5. Interleukin-1β, C-x-C motif ligand 10, and interferon-gamma serum levels in mixed cryoglobulinemia with or without autoimmune thyroiditis.

    PubMed

    Antonelli, Alessandro; Ferri, Clodoveo; Ferrari, Silvia Martina; De Marco, Salvatore; Di Domenicantonio, Andrea; Centanni, Marco; Pupilli, Cinzia; Villa, Erica; Menichetti, Francesco; Fallahi, Poupak

    2010-11-01

    The aim of this study was to evaluate serum levels of interleukin-1β (IL-1β), chemokine (C-X-C motif) ligand 10 (CXCL10), and interferon-gamma (IFN-γ) in a series of patients with "mixed cryoglobulinemia and hepatitis C virus chronic infection" (MC + HCV) in the presence or absence of autoimmune thyroiditis (AT) and to relate them to the clinical phenotype of these patients. Serum IL-1β, IFN-γ, and CXCL10 were assayed in 30 patients with MC + HCV without AT, in 30 patients with MC + HCV and AT, and in 30 sex- and age-matched controls. Cryoglobulinemic patients showed significantly higher mean IL-1β and CXCL10 levels than controls (P < 0.01). Moreover, CXCL10 was significantly increased in patients with AT patients with respect to those without AT (P < 0.01). Serum IFN-γ levels were not significantly higher in MC + HCV patients than in controls. In conclusion, our study demonstrates significantly high serum levels of IL-1β in patients with MC + HCV with and without AT compared with healthy controls. Further, significantly high serum levels of CXCL10 in patients with MC + HCV compared with healthy controls were confirmed, overall in the presence of AT. Moreover, a pathophysiological association between high circulating levels of IL-1β and CXCL10 has been suggested. A possible therapeutic role of the anti-IL-1 receptor antagonist (Anakirna) in MC remains to be evaluated.

  6. Observations on cryoglobulin testing: II. The association of oligoclonal mixed cryoglobulinemia with cirrhosis in patients infected with hepatitis C virus.

    PubMed

    De Rosa, Francesco G; Abel, György; Agnello, Vincent

    2009-09-01

    To determine whether a mixed cryoglobulin type correlated with cirrhosis in patients infected with hepatitis C virus (HCV). We investigated the results of mixed cryoglobulin tests performed in the clinical laboratory on patients with and without HCV infection. A higher prevalence of oligoclonal cryoglobulins designated Type IIa was present in HCV-infected patients with cirrhosis than in those without cirrhosis. An association of Type IIa cryoglobulins with cirrhosis in HCV-infected patients has not previously been reported.

  7. The presence of autoimmune thyroiditis in mixed cryoglobulinemia patients is associated with high levels of circulating interleukin-6, but not of tumor necrosis factor-alpha.

    PubMed

    Antonelli, Alessandro; Ferri, Clodoveo; Ferrari, Silvia Martina; Di Domenicantonio, Andrea; Ferrari, Paola; Pupilli, Cinzia; Nicolini, Andrea; Zignego, Anna Linda; Marchi, Santino; Fallahi, Poupak

    2011-01-01

    To our knowledge, no study has evaluated serum levels of interleukin-6 (IL-6), together with tumour necrosis factor-alpha (TNF-α), in a large series of patients with 'mixed cryoglobulinemia and HCV chronic infection' (MC+HCV) in relation to the presence of autoimmune thyroiditis (AT). The aims of the study were to evaluate serum levels of IL-6 in MC+HCV patients and to correlate this parameter with the presence of AT and with circulating levels of TNF-α. Serum IL-6 and TNF-α were assayed in 41 MC+HCV patients, in 41 MC+HCV patients with autoimmune thyroiditis (MC+AT), in 41 sex- and age-matched controls, and 20 AT patients. MC+HCV patients showed significantly (p<0.01; Mann-Whitney U-test) higher IL-6 (median 8.1ng/l, range 0.7-651) serum levels than controls (median 0.6ng/l, range 0.5-41), or AT (median 2.8ng/l, range 0.5-67). MC+AT showed significantly (p<0.01; Mann-Whitney U-test) higher mean IL-6 (median 15.8ng/l, range 0.5-781) than controls, AT and MC+HCV. Serum TNF-α levels were significantly higher in MC+HCV (median 9.9ng/l, range 1.5-283) or MC+AT (median 11.2ng/l, range 1.6-412) than in controls (median 1.0ng/l, range 0.6-6.4), or AT (median 1.7ng/l, range 0.6-11.8) (p<0.01, for each comparison). Our study demonstrates significantly higher serum levels of IL-6 and TNF-α in patients with MC+HCV and MC+AT compared to healthy controls. Furthermore, the study first shows a significant increase in circulating IL-6 observed in MC+AT patients with respect to MC+HCV. Future studies in larger patients' series will be needed to evaluate the relevance of serum IL-6 and TNF-α determination as clinico-prognostic markers of MC+HCV patients and its usefulness in the therapeutic approach to these patients.

  8. Chronic hepatitis C virus infection and lymphoproliferative disorders: mixed cryoglobulinemia syndrome, monoclonal gammopathy of undetermined significance, and B-cell non-Hodgkin lymphoma.

    PubMed

    Caviglia, Gian Paolo; Sciacca, Claudio; Abate, Maria Lorena; Olivero, Antonella; Rosso, Chiara; Touscoz, Giovanni Antonio; Ciancio, Alessia; Rizzetto, Mario; Smedile, Antonina

    2015-04-01

    Chronic hepatitis C (CHC) has been associated with lymphoproliferative disorders (LPD) such as mixed cryoglobulinemia syndrome (MCS), monoclonal gammopathy of undetermined significance (MGUS), and B-cell non-Hodgkin lymphoma (B-NHL). The aim of the present study is to assess MCS, MGUS, and B-NHL prevalence in a cohort of CHC-infected patients and to evaluate the association of demographic, clinical, and virologic factors with the presence of LPDs. A total of 121 CHC patients with LPDs (50 M, 71 F; mean age 61.5 ± 11.8) and 130 CHC patients without extrahepatic manifestations (60 M, 70 F; mean age 60.4 ± 9.2) were retrospectively enrolled from a cohort of 1313 CHC patients between January 2006 and December 2013. Patients with LPDs included: 25 patients with MCS (9 M, 16 F; mean age 60.2 ± 1.4), 55 patients with MGUS (18 M, 37 F; mean age 61.3 ± 12.1), and 41 patients with B-NHL (23 M, 18F; mean age 62.5 ± 11.0) RESULTS: Patients with MCS (25/1313; 1.9%), MGUS (55/1313; 4.2%), and B-LNH (41/1313; 3.1%) did not differ in age, severity of liver disease, HCV genotype, and response to antiviral therapy. Using multivariate logistic regression analysis, a positive association was found between the presence of cirrhosis and MGUS (odds ratio [OR] = 2.8924, 95% confidence interval [CI] 1.2693-6.5909; P = 0.012) and between cirrhosis and B-NHL (OR = 3.9407, 95% CI 1.7226-9.0153; P = 0.001), whereas no association with MCS diagnosis emerged. Despite the pathogenetic mechanism of HCV-associated LPDs is still unclear, cirrhosis is an additional risk factor for the development of lymphoproliferative disorders in patients with chronic HCV infection. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  9. Cryoglobulinemia manifested by gangraene of almost all fingers and toes.

    PubMed

    Vacula, I; Ambrózy, E; Makovník, M; Stvrtina, S; Babál, P; Stvrtinová, V

    2010-12-01

    Cryoglobulinemia is a rather rare condition accompanying quite a broad spectrum of different states and diseases. Mixed or polyclonal cryoglobulins can be seen in patients with autoimmune disorders, chronic infections and lymphoproliferative disorders. Monoclonal cryoglobulins are often revealed in patients with multiple myeloma or Waldenström's macroglobulinemia. Cryoglobulinemia is in most cases asymptomatic. Cryoglobulinemic vasculitis is an immune complex-mediated systemic disorder involving mostly small, but sometimes also larger vessels. In this report, we describe a case of a patient presented with gangrene of almost all fingers and toes, who was finally diagnosed and treated as cryoglobulinemic vasculitis due to multiple myeloma.

  10. Persistence of orographic mixed-phase clouds

    NASA Astrophysics Data System (ADS)

    Lohmann, U.; Henneberger, J.; Henneberg, O.; Fugal, J. P.; Bühl, J.; Kanji, Z. A.

    2016-10-01

    Mixed-phase clouds (MPCs) consist of ice crystals and supercooled water droplets at temperatures between 0 and approximately -38°C. They are thermodynamically unstable because the saturation vapor pressure over ice is lower than that over supercooled liquid water. Nevertheless, long-lived MPCs are ubiquitous in the Arctic. Here we show that persistent MPCs are also frequently found in orographic terrain, especially in the Swiss Alps, when the updraft velocities are high enough to exceed saturation with respect to liquid water allowing simultaneous growth of supercooled liquid droplets and ice crystals. Their existence is characterized by holographic measurements of cloud particles obtained at the high-altitude research station Jungfraujoch during spring 2012 and winter 2013 and simulations with the regional climate model COSMO (Consortium of Small-Scale Modeling).

  11. Combined Treatment with Antiviral Therapy and Rituximab in Patients with Mixed Cryoglobulinemia: Review of the Literature and Report of a Case Using Direct Antiviral Agents-Based Antihepatitis C Virus Therapy

    PubMed Central

    Urraro, Teresa; Gragnani, Laura; Piluso, Alessia; Fabbrizzi, Alessio; Monti, Monica; Boldrini, Barbara; Ranieri, Jessica; Zignego, Anna Linda

    2015-01-01

    Mixed cryoglobulinemia (MC) is an autoimmune/B-cell lymphoproliferative disorder associated with Hepatitis C Virus (HCV) infection, manifesting as a systemic vasculitis. In the last decade, antiviral treatment (AT) with pegylated interferon (Peg-IFN) plus ribavirin (RBV) was considered the first therapeutic option for HCV-MC. In MC patients ineligible or not responsive to antivirals, the anti-CD20 monoclonal antibody rituximab (RTX) is effective. A combined AT plus RTX was also suggested. Since the introduction of direct acting antivirals (DAAs), few data were published about MC and no data about a combined schedule. Here, we report a complete remission of MC after a sustained virological response following a combined RTX/Peg-IFN+RBV+DAA (boceprevir) treatment and review the literature about the combined RTX/AT. PMID:25815218

  12. Cold agglutinin disease and cryoglobulinemia.

    PubMed

    Gertz, Morie A

    2005-03-01

    Cold agglutinin disease is a form of direct, extravascular, antiglobulin-positive hemolysis. In vivo, immunoglobulin (Ig) M fixes complement molecules to the red cell membrane. Successive passages through the mononuclear phagocyte system result in loss of red cell membrane. The resultant spherocytes lose resiliency and are ultimately lost from the circulation extravascularly. The high concentration of complement molecules on the red cell surfaces makes this syndrome resistant to the standard therapies for immune-mediated hemolysis. Rituximab has been reported to reduce the severity of hemolysis. Type II cryoglobulins are composed of a monoclonal IgM and a polyclonal IgG. These complexes have rheumatoid factor activity and can produce immune-complex vasculitis. The target organs are the skin, nerves, kidney, liver, and joints. More than 80% of patients have evidence of hepatitis C infection. Interferon and interferon plus ribavirin have been shown to produce serologic responses. When vasculitis is active, corticosteroids are often required to permit healing of ulcers in the skin or to treat the membranoproliferative glomerulonephritis that is seen, thereby preventing loss of renal function. Rituximab therapy has been found to be effective in mixed cryoglobulinemia, with decreases in cryoglobulin values and improvement in complement values.

  13. Cryoglobulinemia in chronic liver diseases: role of hepatitis C virus and liver damage.

    PubMed

    Lunel, F; Musset, L; Cacoub, P; Frangeul, L; Cresta, P; Perrin, M; Grippon, P; Hoang, C; Valla, D; Piette, J C

    1994-05-01

    Mixed cryoglobulinemia is frequently associated with liver diseases. The respective role of hepatitis C virus (HCV) and liver damage in the pathogenesis of cryoglobulinemia is investigated in this study. The prevalence of cryoglobulinemia in 226 consecutive patients with chronic liver diseases (hepatitis C, 127; hepatitis B, 40; other diseases, 59) was studied, and the epidemiological, biological, histological, and virological features in these three groups were analyzed. Anti-HCV antibodies, HCV proteins, and HCV RNA were searched in the cryoprecipitates. The prevalence of mixed cryoglobulinemia was high (41.5%) in patients with liver diseases and higher in patients with hepatitis C (54.3%) than in patients with hepatitis B (15%) or other causes of liver disease (32%). Patients with cryoglobulinemia had cirrhosis more frequently and had a longer history of hepatitis. In patients with hepatitis C, HCV RNA sequences and HCV proteins were detected in the cryoprecipitate. Cryoglobulins became undetectable in 21 of 43 patients treated with interferon. These findings suggest that HCV is a major cause of cryoglobulinemia. Besides viral infection itself, multiple factors appear to be responsible for the production of cryoglobulins, including cirrhosis and duration of liver disease.

  14. Lesson from an intriguing case of cryoglobulinemia.

    PubMed

    Barone, Michele; Licinio, Raffaele; Amoruso, Annabianca; Viggiani, Maria Teresa; Larocca, Angela Maria Vittoria; Di Leo, Alfredo

    2013-01-14

    Cryoglobulinemia is a pathological condition usually associated with hepatitis C virus (HCV) chronic liver disease and less commonly with autoimmune or lymphoproliferative disorders. The possible association of cryoglobulinemia with hepatitis B virus (HBV) infection is not widely accepted. In our patient, serum negativity for HCV markers initially led us to consider two other causes of cryoglobulinemia. Myelodysplastic disorders were excluded on the basis of hematological studies, while serum markers for active HBV infection were positive. Surprisingly, the detection of HCV RNA in the cryocrit, even in the absence of anti-HCV antibodies, suggested a pathogenetic role of HCV in this case of cryoglobulinemia. Negative "first level" tests for HCV in the serum do not completely exclude HCV involvement in the pathogenesis of cryoglobulinemia. Analysis of the cryoprecipitate is always essential for diagnosis.

  15. Lesson from an intriguing case of cryoglobulinemia

    PubMed Central

    Barone, Michele; Licinio, Raffaele; Amoruso, Annabianca; Viggiani, Maria Teresa; Larocca, Angela Maria Vittoria; Di Leo, Alfredo

    2013-01-01

    Cryoglobulinemia is a pathological condition usually associated with hepatitis C virus (HCV) chronic liver disease and less commonly with autoimmune or lymphoproliferative disorders. The possible association of cryoglobulinemia with hepatitis B virus (HBV) infection is not widely accepted. In our patient, serum negativity for HCV markers initially led us to consider two other causes of cryoglobulinemia. Myelodysplastic disorders were excluded on the basis of hematological studies, while serum markers for active HBV infection were positive. Surprisingly, the detection of HCV RNA in the cryocrit, even in the absence of anti-HCV antibodies, suggested a pathogenetic role of HCV in this case of cryoglobulinemia. Negative “first level” tests for HCV in the serum do not completely exclude HCV involvement in the pathogenesis of cryoglobulinemia. Analysis of the cryoprecipitate is always essential for diagnosis. PMID:23345955

  16. CD21(-/low) marginal zone B cells highly express Fc receptor-like 5 protein and are killed by anti-Fc receptor-like 5 immunotoxins in hepatitis C virus-associated mixed cryoglobulinemia vasculitis.

    PubMed

    Terrier, Benjamin; Nagata, Satoshi; Ise, Tomoko; Rosenzwajg, Michelle; Pastan, Ira; Klatzmann, David; Saadoun, David; Cacoub, Patrice

    2014-02-01

    Hepatitis C virus (HCV) is associated with B cell lymphoproliferative disorders, including mixed cryoglobulinemia (MC) vasculitis and B cell non-Hodgkin's lymphoma. The expansion of clonal and autoreactive rheumatoid factor-bearing CD21(-/low) marginal zone (MZ) B cells was demonstrated in patients with HCV-associated MC vasculitis. Fc receptor-like (FCRL) proteins comprise a family of immunoregulatory proteins preferentially expressed on B lineage cells. The goal of this study was to investigate the expression of FCRL proteins 1-5 on B cells from patients with HCV-associated MC vasculitis. Expression of FCRL proteins 1-5 was assessed by flow cytometry on B cells from 15 HCV-infected patients with type II MC (7 of whom had B cell non-Hodgkin's lymphoma), 20 HCV-infected patients without MC, and 20 healthy donors. To evaluate FCRL-5 as an immunotherapy target in HCV-associated MC vasculitis, 2 anti-FCRL-5 recombinant immunotoxins were produced using anti-FCRL-5 monoclonal antibodies and Pseudomonas exotoxin. Expression of FCRLs 2, 3, and 5 was markedly increased while expression of FCRL-1 was decreased on clonal CD21(-/low) MZ B cells, as compared with other B cell subsets, from HCV-infected patients and healthy donors. However, there was no difference in the pattern of FCRL expression between HCV-MC patients with lymphoma and those without lymphoma. The anti-FCRL-5 immunotoxins showed specific cytotoxicity against FCRL-5-expressing clonal CD21(-/low) MZ B cells isolated from HCV-infected patients as well as FCRL-5-transfected cell lines. No cytotoxicity against T cells or conventional B cells was observed. These findings suggest that FCRL-5-targeting therapies could be a specific treatment for HCV-associated MC vasculitis and other FCRL-5-positive autoimmune B cell disorders. Copyright © 2014 by the American College of Rheumatology.

  17. Resolution of Q Fever–Associated Cryoglobulinemia With Anti-CD20 Monoclonal Antibody Treatment

    PubMed Central

    Hawkins, Kellie L.; Janoff, Edward N.; Janson, Robert W.

    2017-01-01

    Immunologic phenomena can complicate chronic infections with Coxiella burnetii (Q fever), including immune complex deposition causing vasculitis, neuropathy, and glomerulonephritis. We describe the case of a man with Q fever endocarditis, mixed cryoglobulinemia, and life-threatening vasculitis driven by immune complex deposition who was successfully treated with B cell depleting therapy (rituximab). PMID:28203574

  18. Hepatitis C virus, cryoglobulinemia, and kidney: novel evidence.

    PubMed

    Fabrizi, Fabrizio

    2012-01-01

    Hepatitis C virus infection can lead to chronic active hepatitis, cirrhosis, and liver failure; however, it is also associated with a wide range of extra-hepatic complications. HCV is associated with a large spectrum of histopathological lesions in both native and transplanted kidneys, and it is increasingly recognized as an instigator of B cell lympho-proliferative disorders including mixed cryoglobulinemia. Mixed cyoglobulinemia is a systemic vasculitis primarily mediated by immune complexes; it is characterized by variable organ involvement including skin lesions, chronic hepatitis, glomerulonephritis, peripheral neuropathy, and arthralgias. The most frequent HCV-associated nephropathy is type I membranoproliferative glomerulonephritis, usually in the context of type II mixed cryoglobulinemia. Various approaches have been tried for the treatment of HCV-related glomerulonephritis, including immunosuppressive therapy (corticosteroids and cytotoxic agents), plasma exchange and antiviral agents. Data on the antiviral treatment of HCV-associated glomerulonephritis are not abundant but encouraging results have been provided. Immunosuppressive therapy is particularly recommended for cryoglobulinemic kidney disease. Recent evidence has been accumulated on rituximab therapy for HCV-related cryoglobulinemic glomerulonephritis exists but several questions related to its use remain unclear. Distinct approaches should be considered for the treatment of HCV-associated cryoglobulinemic glomerulonephritis according to the level of proteinuria and kidney failure.

  19. Hepatitis C Virus, Cryoglobulinemia, and Kidney: Novel Evidence

    PubMed Central

    Fabrizi, Fabrizio

    2012-01-01

    Hepatitis C virus infection can lead to chronic active hepatitis, cirrhosis, and liver failure; however, it is also associated with a wide range of extra-hepatic complications. HCV is associated with a large spectrum of histopathological lesions in both native and transplanted kidneys, and it is increasingly recognized as an instigator of B cell lympho-proliferative disorders including mixed cryoglobulinemia. Mixed cyoglobulinemia is a systemic vasculitis primarily mediated by immune complexes; it is characterized by variable organ involvement including skin lesions, chronic hepatitis, glomerulonephritis, peripheral neuropathy, and arthralgias. The most frequent HCV-associated nephropathy is type I membranoproliferative glomerulonephritis, usually in the context of type II mixed cryoglobulinemia. Various approaches have been tried for the treatment of HCV-related glomerulonephritis, including immunosuppressive therapy (corticosteroids and cytotoxic agents), plasma exchange and antiviral agents. Data on the antiviral treatment of HCV-associated glomerulonephritis are not abundant but encouraging results have been provided. Immunosuppressive therapy is particularly recommended for cryoglobulinemic kidney disease. Recent evidence has been accumulated on rituximab therapy for HCV-related cryoglobulinemic glomerulonephritis exists but several questions related to its use remain unclear. Distinct approaches should be considered for the treatment of HCV-associated cryoglobulinemic glomerulonephritis according to the level of proteinuria and kidney failure. PMID:24278667

  20. Cryoglobulinemia

    MedlinePlus

    ... inflammation of the blood vessels throughout the body (vasculitis). There are three main types of this condition. ... Skin biopsy -- may show inflammation in blood vessels, vasculitis. Protein electrophoresis - blood -- may show an abnormal antibody ...

  1. Cryoglobulinemia

    MedlinePlus

    ... you think. More serious than you know. Support. Awareness. Education. Become a member today! Our Mission The ... Foundation supports and empowers our community through education, awareness and research. Contact Us Click here to send ...

  2. High values of CXCL10 serum levels in patients with hepatitis C associated mixed cryoglobulinemia in presence or absence of autoimmune thyroiditis.

    PubMed

    Antonelli, Alessandro; Ferri, Clodoveo; Fallahi, Poupak; Ferrari, Silvia Martina; Frascerra, Silvia; Sebastiani, Marco; Franzoni, Ferdinando; Galetta, Fabio; Ferrannini, Ele

    2008-04-01

    The aim of this study was to evaluate CXCL10 serum levels in patients with hepatitis C virus chronic infection (HCV) associated mixed cyoglobulinemia (MC), in the presence or absence of autoimmune thyroiditis (AT). CXCL10 was assayed in 50 MC patients without AT, in 40 MC patients with AT (MC+AT), in 2 gender- and age-matched control groups [50 healthy controls (without HCV or AT; control); 40 controls with AT (without HCV and MC; control+AT)]. CXCL10 was significantly higher: (1) in control+AT than in control (p<0.001); (2) in MC patients than in control (p<0.001); (3) in MC+AT patients than in control (p<0.001), control+AT (p<0.001), or in MC (p=0.002). CXCL10 was significantly increased in MC+AT patients with thyroid hypoechogenicity (388+/-147 vs 302+/-112; p=0.03), or hypothyroidism (391+/-142 vs 307+/-118; p=0.04), compared to those without. By defining a high CXCL10 level as a value at least 2 SD above the mean value of the control (>167 pg/ml), 8% of control, 22% of control+AT, 47% of MC and 80% of MC+AT had high CXCL10 (p<0.0001). In conclusion, our study is the first to demonstrate high serum levels of CXCL10 in MC and that CXCL10 in MC+AT patients are significantly higher compared to MC patients.

  3. Absence of antibodies to cyclic citrullinated peptide in sera of patients with hepatitis C virus infection and cryoglobulinemia.

    PubMed

    Wener, Mark H; Hutchinson, Kathleen; Morishima, Chihiro; Gretch, David R

    2004-07-01

    To determine if antibodies to cyclic citrullinated peptide (anti-CCP) are found in chronic hepatitis C virus (HCV) infection. Rheumatoid factor (RF) and anti-CCP were measured in sera from 50 patients with HCV infection but without cryoglobulinemia, sera from 29 patients with mixed cryoglobulinemia (including 13 with rheumatic symptoms and 5 with arthritis), and sera from 20 normal blood donors. Anti-CCP was measured by second-generation enzyme-linked immunosorbent assay (ELISA). No sera with elevated anti-CCP were found in patients with HCV infection without cryoglobulinemia, and in that population, the maximum anti-CCP was 10 units, well below the positive cutoff of 20 units. Positive findings on RF testing >13 IU/ml were present in 22 (44%) of the HCV patients, with RF >50 IU/ml in 8 (16%) and a maximum RF of 526 IU/ml. Of the cryoglobulinemia patients, 22 (76%) had positive results on tests for RF, including 18 (62%) with RF >50 IU/ml and a maximum RF of 5,540 IU/ml. Two (6.9%) of the cryoglobulinemia patients had borderline-positive findings on tests for anti-CCP (25 units and 37 units), which were false-positive results caused by nonspecific binding in the ELISA. No association between the RF and the anti-CCP concentrations was found. Whereas RF was frequent in patients with HCV infection with and without cryoglobulinemia, anti-CCP was not observed in patients with uncomplicated HCV infection. Borderline-positive anti-CCP results were observed infrequently in patients with mixed cryoglobulinemia and were caused by nonspecific binding to plastic. Measurement of anti-CCP may help in diagnosing RA in patients with chronic HCV infection.

  4. Treatment of mixed cryoglobulinemia: a rheumatology perspective.

    PubMed

    De Vita, Salvatore

    2011-01-01

    The treatment of the cryoglobulinemic syndrome or vasculitis (CV) must be targeted to the individual patient, and requires clinical expertise and knowledge of the disease biology. In general, the treatment is suggested by the clinical picture, but biologic issues should also be considered. Both immunosuppressive and antiviral approaches deserve equal attention based on the wide clinical spectrum and on disease biology, where the viral trigger and the downstream autoimmune response may play a different role in different disease stages. The severity of the disease, previous history and therapies administered, comorbidities and other individual factors should be analysed in the single case. Acute and life-threatening conditions usually require high dose steroids, plasmapheresis and/or cyclophosphamide. Rituximab often represents the best option for severe CV. Antiviral therapy is a cornerstone for the management of CV in hepatitis-related cases, and has the strongest biologic rationale, in general, in this disease and should be always considered in stabilised patients. A multispecialistic approach is needed to better define treatment strategies in different subsets of patients.

  5. [Hepatitis-C-virus-associated cryoglobulinemia. Pathogenesis, diagnosis and treatment].

    PubMed

    Staak, Jan Oliver; Glossmann, Jan-Peter; Diehl, Volker; Josting, Andreas

    2002-10-15

    Chronic hepatitis C-virus (HCV) infection is frequently associated with a variety of autoimmune phenomenons. Mixed cryoglobulins appear in up to 50% of chronic HCV-infected patients, mostly asymptomatic. Cryoprecipitates present IgM with rheumatoid factor activity and development of immunocomplexes deposited in small vessels responsible for resulting vasculitis. MANIFESTATIONS: Characteristic clinical findings are weakness, arthralgia and purpura with further complications including glomerulonephritis and neuropathic lesions. Several mechanisms for HCV-induced clinical lymphoproliferation are discussed, such as chronic B-cell stimulation and activation of the antiapoptotic oncogene bcl-2 leading to immunoglobulin synthesis and eventually evolving into B-cell non-Hodgkin's lymphoma (NHL). Conventional treatment of HCV-associated mixed cryoglobulinemia aimes at reducing circulating immunocomplexes and causal therapy with interferon (IFN) and ribavirin. New approaches using the anti-CD20 antibody rituximab have been described recently.

  6. Prevalence of cryoglobulinemia and autoimmune markers in liver transplant patients.

    PubMed

    Garrouste, Cyril; Kamar, Nassim; Boulestin, Anne; Esposito, Laure; Lavayssiere, Laurence; Durand, Dominique; Blancher, Antoine; Rostaing, Lionel

    2008-09-01

    To examine the prevalence of cryoglobulinemia and autoimmune markers in stable liver transplant recipients and to determine risk factors and clinical impact. Ninety-two liver transplant recipients were tested for cryoglobulinemia, hepatitis B and C, complement C3, complement C4, CH50, antinuclear antibodies, anticytoplasmic neutrophil antibodies, anticardiolipid antibodies, rheumatoid factors, and lymphocyte subpopulations. Liver, renal, and hematology tests were done. Immunosuppressive regimens were based on calcineurin inhibitors in 94.6% of the patients. Cryoglobulinemia was present in 18 patients (19.5%) with characteristics of type II in 27.7%, type III in 61.3%, and indeterminate in 11%. Cryoglobulinemia was present in 55.5% of patients with positive hepatitis C virus serology compared with 35.86% of patients with negative hepatitis C virus serology (P = .06). Among those with hepatitis C virus markers, cryoglobulinemia was present in 30%. Anticytoplasmic neutrophil antibodies were positive in 23% of the patients with cryoglobulinemia, but in only 5.4% of the patients without cryoglobulinemia (P = .006). Albuminemia was significantly lower in patients with cryoglobulinemia (38 -/+ 4.2 g/L) than it was in patients without cryoglobulinemia (40.2 -/+ 3.4; P = .05). Cryoglobulinemia was symptomatic in 4 patients (22.2% of all patients). Independent factors associated with cryoglobulinemia were presence of anticytoplasmic neutrophil antibodies, more than 4 HLA incompatibilities, alanine aminotransferase level of 0.68 microkat/L or more, and an albuminemia level greater than 38 g/L. Cryoglobulinemia is frequent after liver transplant and is symptomatic in approximately 20% of all patients.

  7. Necrotizing acute pancreatitis following therapeutic plasmapheresis in HCV-related cryoglobulinemia.

    PubMed

    Desideri, F; Van Vlierberghe, H

    2011-06-01

    Mixed cryoglobulinemia and hepatitis C virus infection are strongly connected and the therapeutic approach is standardized according to the severity of the symptoms. We report the difficult management of 59 year old female HCV patient presenting cutaneous lesions and arthralgia due to mixed cryoglobulinemia. No therapy was able to achieve a complete remission and during the six years of active disease we observed several clinical recurrences. The intensive plasmapheresis regimen led to a complete remission of the symptoms but it was associated with severe complications. In this case report we describe an episode of acute necrotizing pancreatitis due to intravascular haemolysis following therapeutic plasmapheresis. To the best of our knowledge the association between plasmapheresis and acute pancreatitis has not been previously described.

  8. Secondary Science Teachers' Beliefs and Persistence: A Longitudinal Mixed-Methods Study

    ERIC Educational Resources Information Center

    Wong, Sissy S.; Luft, Julie A.

    2015-01-01

    While many studies focus on why teachers leave the classroom, there remains a need to study why teachers persist in teaching. One area to study is the beliefs of teachers, which may impact persistence in the field. This 5-year mixed-methods study explored whether 35 beginning secondary science teachers' beliefs were related to their persistence in…

  9. Secondary Science Teachers' Beliefs and Persistence: A Longitudinal Mixed-Methods Study

    ERIC Educational Resources Information Center

    Wong, Sissy S.; Luft, Julie A.

    2015-01-01

    While many studies focus on why teachers leave the classroom, there remains a need to study why teachers persist in teaching. One area to study is the beliefs of teachers, which may impact persistence in the field. This 5-year mixed-methods study explored whether 35 beginning secondary science teachers' beliefs were related to their persistence in…

  10. Thymic stromal lymphopoietin transgenic mice develop cryoglobulinemia and hepatitis with similarities to human hepatitis C liver disease.

    PubMed

    Kowalewska, Jolanta; Mühlfeld, Anja S; Hudkins, Kelly L; Yeh, Matthew M; Farr, Andrew G; Ravetch, Jeffrey V; Alpers, Charles E

    2007-03-01

    Essential mixed cryoglobulinemia in humans is strongly associated with chronic hepatitis C virus infection. It remains controversial whether liver injury in hepatitis C is primarily attributable to direct viral cytopathic effect or to an immune-mediated response. We characterized the role of cryoglobulinemia in the development of liver disease in thymic stromal lymphopoietin (TSLP) transgenic mice that produce mixed cryoglobulinemia and develop hepatitis. The role of immune complexes in this animal model was evaluated using techniques of light, immunofluorescence, and electron microscopy. To assess the role of Fc receptor engagement in mediation of the disease, TSLP transgenic mice were crossbred with mice deficient for immunoglobulin-binding receptor gamma IIb (FcgammaRIIb). Livers from the TSLP transgenic animals showed mild to moderate liver injury, minimal to mild fibrosis, and deposition of immunoglobulin around the portal tracts. TSLP transgenic mice deficient in inhibitory FcgammaRIIb had more severe hepatitis and accelerated mortality. TSLP-associated hepatitis bears strong similarity to hepatitis C virus-related hepatitis as it occurs in humans, making this a valuable model system of chronic hepatitis and fibrosis to study therapies aimed at manipulating immune responses. Periportal immune complex deposition may play an important role in the pathogenesis of hepatitis occurring in the setting of systemic cryoglobulinemia.

  11. Thymic Stromal Lymphopoietin Transgenic Mice Develop Cryoglobulinemia and Hepatitis with Similarities to Human Hepatitis C Liver Disease

    PubMed Central

    Kowalewska, Jolanta; Mühlfeld, Anja S.; Hudkins, Kelly L.; Yeh, Matthew M.; Farr, Andrew G.; Ravetch, Jeffrey V.; Alpers, Charles E.

    2007-01-01

    Essential mixed cryoglobulinemia in humans is strongly associated with chronic hepatitis C virus infection. It remains controversial whether liver injury in hepatitis C is primarily attributable to direct viral cytopathic effect or to an immune-mediated response. We characterized the role of cryoglobulinemia in the development of liver disease in thymic stromal lymphopoietin (TSLP) transgenic mice that produce mixed cryoglobulinemia and develop hepatitis. The role of immune complexes in this animal model was evaluated using techniques of light, immunofluorescence, and electron microscopy. To assess the role of Fc receptor engagement in mediation of the disease, TSLP transgenic mice were crossbred with mice deficient for immunoglobulin-binding receptor γ IIb (FcγRIIb). Livers from the TSLP transgenic animals showed mild to moderate liver injury, minimal to mild fibrosis, and deposition of immunoglobulin around the portal tracts. TSLP transgenic mice deficient in inhibitory FcγRIIb had more severe hepatitis and accelerated mortality. TSLP-associated hepatitis bears strong similarity to hepatitis C virus-related hepatitis as it occurs in humans, making this a valuable model system of chronic hepatitis and fibrosis to study therapies aimed at manipulating immune responses. Periportal immune complex deposition may play an important role in the pathogenesis of hepatitis occurring in the setting of systemic cryoglobulinemia. PMID:17322382

  12. Characterization of antibodies directed against the immunoglobulin light kappa chain variable chain region (VK) of hepatitis C virus-related type-II mixed cryoglobulinemia and B-cell proliferations.

    PubMed

    de Re, Valli; Simula, Maria Paola; Pavan, Alessandro; Garziera, Marica; Marin, Dolores; Dolcetti, Riccardo; de Vita, Salvatore; Sansonno, Domenico; Geremia, Silvano; Toffoli, Giuseppe

    2009-09-01

    Autoimmune type-II cryoglobulinemia (II-MC) is sustained by hepatitis C virus (HCV) infection and B-cell (oligo)clones. This is the reason why the disease may be considered an "indolent B-cell lymphoma (NHL)." B clones show a restricted use of immunoglobulin variable genes (BCR), in particular in the use of the variable kappa (VK)3-20/15 light chain, and show a homology between their BCR functional regions and those of autoimmune rheumatoid factors. We underlined the BCR unique repertoire with frequent rheumatoid factor activity also observed in other autoimmune disorders associated with NHL. The immunoglobulin idiotype is a clonal B-cell marker and an ideal target for immunotherapy. Five monoclonal antibodies were produced in our laboratory toward the VK3-20 of a subject with HCV infection and a II-MC-associated NHL. Epitope determination was performed using the epitope excision approach. Monoclonal antibody reactivity was tested in vitro in ELISA, Western blot, and cytofluorimetry. Data confirmed that a panel of antibodies, reactive against shared idiotypes, can be produced from patients with HCV-associated B-cell lymphoproliferative diseases, thus obviating the need to produce an anti-idiotype antibody for each patient.

  13. A systemic lupus erythematosus patient presenting as type B insulin resistance complicated with cryoglobulinemia.

    PubMed

    Huang, Q; Yan, Y; Zhao, H; Zuo, L

    2017-01-01

    Systemic lupus erythematosus (SLE) patients may present with various symptoms and multisystem damage. We reported a 63-year-old male patient with SLE presenting as type B insulin resistance (TBIR) complicated with cryoglobulinemia. TBIR is an extremely rare disease, which is a manifestation of anti-insulin receptor antibodies (AIRA). Clinical feature is a sudden onset of hyperglycemia with major weight loss; however, the ensuing refractory hypoglycemia is more fatal. The average dosage of exogenous insulin is 5100 U/d. SLE patients with AIRA had poor prognosis, most of whom died of SLE activity. Cryoglobulins are immunoglobulins that reversibly precipitate in the cold, which will induce clinical symptoms. Non-infectious mixed cryoglobulinemia is frequently secondary to autoimmune diseases, such as SLE. Our patient was prescribed methylprednisolone (MP) and cyclophosphamide (CTX). Finally he had remission during the short-term follow-up. To our knowledge, this is the first case report of an SLE patient presenting as TBIR complicated with cryoglobulinemia.

  14. Cryoglobulinemia and progression of fibrosis in chronic HCV infection: cause or effect?

    PubMed

    Siagris, Dimitrios; Christofidou, Myrto; Tsamandas, Athanasios; Lekkou, Alexandra; Thomopoulos, Konstantinos; Labropoulou-Karatza, Chryssoula

    2004-10-01

    Mixed cryoglobulinemia (MC) is the most common extrahepatic manifestation of HCV infection. The aim of this study is to determine the prevalence of MC in HCV infected Greek patients and to identify if it is associated with liver histology or the mode of HCV transmission. One hundred and twenty-six patients with chronic HCV infection were evaluated for the presence of serum cryoglobulins, autoantibodies and viral markers. One hundred and eighteen of them underwent liver biopsy and each specimen was evaluated according to the grading and staging system described by Ishak et al. Cryoglobulins were detected in 37/126 (29.4%) HCV patients and cryocrit values ranged between 0.5 and 6.5%. Only two patients presented clear clinical manifestations of MC. In patients with MC, a higher grading (6.40+/-2.06 vs. 5.27+/-2.55, p=0.013) and staging score (3.71+/-1.45 vs. 2.83+/-1.84, p=0.007) was noted in liver biopsy compared to those without MC. Logistic regression analysis identified staging score (OR, 1.33; CI, 1.06-1.66, p=0.015) as the only independent variable associated with cryoglobulinemia. Correlation between the presence of cryoglobulins and the mode of HCV transmission was not found. Greek patients with chronic HCV infection have high prevalence of cryoglobulinemia. A clear association between the presence of serum cryoglobulins and staging score of chronic hepatitis was found, with no difference in patients' age or the duration of infection. It is possible that cryoglobulinemia results in more rapid hepatic fibrosis in HCV infected patients.

  15. [Cryoglobulinemia and the α-chemokine IP-10].

    PubMed

    Corrado, A; Mazzi, V; Ferrari, S M; Politti, U; Giuggioli, D; Antonelli, A; Fallahi, P; Ferri, C

    2014-01-01

    IFN-γ-induced protein 10 (IP-10) and its receptor, CXCR3 chemokine (C-X-C motif) receptor 3 (CXCR3), appear to contribute to the pathogenesis of HCV related mixed cryoglobulinemia (HCV+MC). The secretion of IP-10 by CD4+, CD8+ and natural killer (NK)-T cells is dependent on interferon (IFN)-γ, which is itself mediated by the interleukin (IL)-12 cytokine family. Under the influence of IFN-γ, IP-10 is secreted by several cell types including lymphocytes, hepatocytes, endothelial cells, fibroblasts, etc. In tissues, recruited T helper (Th) 1 lymphocytes may be responsible for enhanced IFN-γ and tumor necrosis factor (TNF)-α production, which in turn stimulates IP-10 secretion from the cells, therefore creating an amplification feedback loop, and perpetuating the autoimmune process. High levels circulation of IP-10 have been found in HCV+MC, especially in patients with clinically active vasculitis. Furthermore, HCV+MC patients with autoimmune thyroiditis (AT), have higher levels than those without AT. Further studies are needed to investigate interactions between chemokines and cytokines in the pathogenesis, and to evaluate whether IP-10 is a novel therapeutic target in HCV+MC.

  16. Social Capital, Socioeconomic Status, and Community College Transfer Student Persistence: A Mixed Methods Study

    ERIC Educational Resources Information Center

    Bouck, Gregory Martin

    2012-01-01

    American students are increasingly beginning higher education pursuits at community colleges before transferring to four-year universities. The purpose of this study was to identify differences in persistence rates between those students who participated in a transfer transition program and those who did not. The researcher adopted a mixed-methods…

  17. Secondary Science Teachers' Beliefs and Persistence: A Longitudinal Mixed-Methods Study

    NASA Astrophysics Data System (ADS)

    Wong, Sissy S.; Luft, Julie A.

    2015-11-01

    While many studies focus on why teachers leave the classroom, there remains a need to study why teachers persist in teaching. One area to study is the beliefs of teachers, which may impact persistence in the field. This 5-year mixed-methods study explored whether 35 beginning secondary science teachers' beliefs were related to their persistence in teaching. Quantitative analysis of the teachers' responses to annual semi-structured interviews revealed that teachers with more student-centered beliefs were more likely to persist at the end of the third year of teaching. Additionally, the teaching beliefs of teachers were more teacher-centered, while the learning beliefs of teachers were more student-centered. A case study of one persisting teacher and one non-persisting teacher revealed that personal experiences and knowledge impacted beliefs about teaching and learning. Bruce, who had extensive inquiry-based school experiences, believed in teaching via student-centered methods. Oscar, who underwent mostly direct instruction during his school experiences, believed in teacher-centered instruction and focused on classroom management. This longitudinal study contributes to the field of science education by examining beginning secondary science teacher persistence over time. Implications from this study call for challenging teacher beliefs during the induction period, proper placement of new teachers into their first teaching positions, and understanding the impact of prior experiences on teachers' beliefs.

  18. Circulating CXCL11 and CXCL10 are increased in hepatitis C-associated cryoglobulinemia in the presence of autoimmune thyroiditis.

    PubMed

    Antonelli, Alessandro; Fallahi, Poupak; Ferrari, Silvia Martina; Sebastiani, Marco; Manfredi, Andreina; Mazzi, Valeria; Fabiani, Silvia; Centanni, Marco; Marchi, Santino; Ferri, Clodoveo

    2012-09-01

    No data are available about circulating levels of the CXCL11 chemokine in hepatitis C virus (HCV)-associated mixed cryoglobulinemia (MC) patients with or without autoimmune thyroiditis (AT). The aim of the present study, therefore, was to evaluate serum CXCL11 levels in these patients. Serum CXCL11 (and for comparison, CXCL10) was measured in 45 patients with MC, 45 patients with MC and AT (MC + AT), 45 sex- and age-matched controls without AT (control 1), 45 sex- and age-matched patients with AT without cryoglobulinemia (control 2), and in 45 sex- and age-matched patients with hepatitis C chronic infection without MC (HCV+). Serum CXCL11 and CXCL10 levels were significantly higher in control 2 than in control 1 (p < 0.01). MC patients had CXCL11 and CXCL10 significantly higher than control 1 (p < 0.01). MC + AT patients had CXCL11 and CXCL10 higher than control 2 (p < 0.01) and MC patients (p = 0.02). Serum CXCL11 levels were not associated with any of the clinical features of cryoglobulinemia in patients with MC and MC + AT, which was the same for CXCL10. CXCL10 and CXCL11 in HCV+ patients were significantly higher than in controls 1 and 2, but lower than in MC or MC+AT patients. Our study first demonstrates higher serum levels of CXCL11 chemokine in patients with MC than in HCV+ patients, and in particular in the presence of AT.

  19. Enhanced Activation of Memory, but Not Naïve, B Cells in Chronic Hepatitis C Virus-Infected Patients with Cryoglobulinemia and Advanced Liver Fibrosis

    PubMed Central

    Santer, Deanna M.; Ma, Mang M.; Hockman, Darren; Landi, Abdolamir; Tyrrell, D. Lorne J.; Houghton, Michael

    2013-01-01

    Mixed cryoglobulinemia is the most common extrahepatic disease manifestation of chronic hepatitis C virus (HCV) infection, where immunoglobulins precipitate at low temperatures and cause symptoms such as vasculitis, glomerulonephritis and arthralgia. HCV-associated cryoglobulinemia is also strongly linked with the development of B cell non-Hodgkin lymphoma. Abnormal B cell function in HCV infections can lead to the formation of HCV cryoglobulin complexes that usually comprise monoclonal rheumatoid factor and HCV-specific immune complexes. The aim of this study was to characterize the activation phenotype of B cells from patients with chronic HCV infection in comparison to healthy controls using flow cytometry. In addition, we determined how the activation status varies depending on the presence of cryoglobulinemia and advanced liver fibrosis. We found that only memory B cells, not naïve cells, were significantly activated in chronic HCV infection when compared with healthy controls. We also identified markers of memory B cell activation that were specific for HCV patients with cryoglobulinemia (CD86, CD71, HLA-DR) and advanced liver disease (CD86). Our results demonstrate that HCV infection has differential effects on B cells depending on the severity of hepatic and extrahepatic disease. PMID:23840845

  20. Enhanced activation of memory, but not naïve, B cells in chronic hepatitis C virus-infected patients with cryoglobulinemia and advanced liver fibrosis.

    PubMed

    Santer, Deanna M; Ma, Mang M; Hockman, Darren; Landi, Abdolamir; Tyrrell, D Lorne J; Houghton, Michael

    2013-01-01

    Mixed cryoglobulinemia is the most common extrahepatic disease manifestation of chronic hepatitis C virus (HCV) infection, where immunoglobulins precipitate at low temperatures and cause symptoms such as vasculitis, glomerulonephritis and arthralgia. HCV-associated cryoglobulinemia is also strongly linked with the development of B cell non-Hodgkin lymphoma. Abnormal B cell function in HCV infections can lead to the formation of HCV cryoglobulin complexes that usually comprise monoclonal rheumatoid factor and HCV-specific immune complexes. The aim of this study was to characterize the activation phenotype of B cells from patients with chronic HCV infection in comparison to healthy controls using flow cytometry. In addition, we determined how the activation status varies depending on the presence of cryoglobulinemia and advanced liver fibrosis. We found that only memory B cells, not naïve cells, were significantly activated in chronic HCV infection when compared with healthy controls. We also identified markers of memory B cell activation that were specific for HCV patients with cryoglobulinemia (CD86, CD71, HLA-DR) and advanced liver disease (CD86). Our results demonstrate that HCV infection has differential effects on B cells depending on the severity of hepatic and extrahepatic disease.

  1. Successful Treatment of Pyoderma Gangrenosum with Cryoglobulinemia and Hepatitis C

    PubMed Central

    Pourmorteza, Mohsen; Tawadros, Fady; Bader, Gilbert; Al-Tarawneh, Mohammad; Cook, Emilie; Shams, Wael; Young, Mark

    2016-01-01

    Patient: Male, 68 Final Diagnosis: Pyoderma gangrenosum Symptoms: Worsening lower extremity wound Medication: — Clinical Procedure: — Specialty: Infectious Diseases Objective: Rare disease Background: Pyoderma gangrenosum is a rare, ulcerative cutaneous condition that was first described by Brocq in 1916. This diagnosis is quite challenging as the histopathological findings are nonspecific. Pyoderma gangrenosum is usually associated with inflammatory bowel disease, leukemia, and hepatitis C. We describe a rare clinical case of a patient with hepatitis C (HCV), mixed cryoglubinemia, and pyoderma gangrenosum, which was successfully treated with prednisone in combination with the new antiviral medication ledipasvir/sofosbuvir. Case Report: A 68-year-old male with a history of untreated HCV presented to the clinic with a left lower extremity ulcer that had progressively worsened over 4 days after the patient sustained a minor trauma to the left lower extremity. Examination revealed a 2×3 cm purulent ulcer with an erythematous rim on medial aspect of his left lower leg. HCV viral load and genotype analysis revealed genotype 1A with polymerase chain reaction (PCR) showing viral counts of 9,506,048 and cryoglobulinemia. With a worsening and enlarging erythematous ulcer and failure of IV antibiotic therapy, the patient underwent skin biopsy, which showed acanthotic epidermis with superficial and deep perivascular lymphoplasmacytic dermatitis admixed with mild neutrophilic infiltrate. The patient was subsequently started on ledipasvir/sofosbuvir and prednisone with a high suspicion of pyoderma gangrenosum. At one-month follow-up at the hepatology clinic, the patient demonstrated a near resolution of the lower extremity ulcer with undetectable viral load. Conclusions: Pyoderma gangrenosum is an inflammatory process of unknown etiology, and establishing the correct diagnosis can be a difficult task. For this reason it is prudent for clinicians to consider Pyoderma

  2. Stories of staying and leaving: A mixed methods analysis of biology undergraduate choice, persistence, and departure

    NASA Astrophysics Data System (ADS)

    Lang, Sarah Adrienne

    Using a sequential, explanatory mixed methods design, this dissertation study compared students who persist in the biology major (persisters) with students who leave the biology major (switchers) in terms of how their pre-college experiences, college biology experiences, and biology performance figured into their choice of biology and their persistence in or departure from the biology major. This study combined (1) quantitative comparisons of biology persisters and switchers via a questionnaire developed for the study and survival analysis of a larger population of biology freshmen with (2) qualitative comparison of biology switchers and persisters via semi-structured life story interviews and homogenous focus groups. 319 students (207 persisters and 112 switchers) participated in the questionnaire and 36 students (20 persisters and 16 switchers) participated in life story and focus group interviews. All participants were undergraduates who entered The University of Texas at Austin as biology freshmen in the fall semesters of 2000 through 2004. Findings of this study suggest: (1) Regardless of eventual major, biology students enter college with generally the same suite of experiences, sources of personal encouragement, and reasons for choosing the biology major; (2) Despite the fact that they have also had poor experiences in the major, biology persisters do not actively decide to stay in the biology major; they simply do not leave; (3) Based upon survival analysis, biology students are most at-risk of leaving the biology major during the first two years of college and if they are African-American or Latino, women, or seeking a Bachelor of Arts degree (rather than a Bachelor of Science); (4) Biology switchers do not leave biology due to preference for other disciplines; they leave due to difficulties or dissatisfaction with aspects of the biology major, including their courses, faculty, and peers; (5) Biology performance has a differential effect on persistence in

  3. Hepatitis C virus infection, cryoglobulinemia, and peripheral neuropathy: a case report.

    PubMed

    Vigani, A G; Macedo-de-Oliveira, A; Pavan, M H P; Pedro, M N; Gonçales Jr, F L

    2005-12-01

    Hepatitis C virus (HCV) is essentially hepatotropic but its manifestations can extend beyond the liver. It can be associated with autoimmune diseases, such as mixed cryoglobulinemia, membranoproliferative glomerulonephritis, autoimmune thyroiditis, and lymphoproliferative disorders. The mechanisms that trigger these manifestations are not completely understood. We describe a 48-year-old man with chronic HCV infection (circulating HCV RNA and moderate hepatitis as indicated by liver biopsy), cryoglobulinemia, and sensory and motor peripheral neuropathy. The diagnosis of multineuropathy was confirmed by clinical examination and electromyographic tests. A nerve biopsy revealed an inflammatory infiltrate in the perineurial space and signs of demyelination and axonal degeneration. The patient had no improvement of neurological symptoms with the use of analgesics and neuro-modulators. He was then treated with interferon-alpha (3 million units subcutaneously, 3 times per week) and ribavirin (500 mg orally, twice a day) for 48 weeks. Six months after the end of therapy, the patient had sustained viral response (negative HCV RNA) and remission of neurological symptoms, but cryoglobulins remained positive. A review of the literature on the pathogenesis and treatment of neurological manifestations associated with HCV infection is presented. This report underscores the need for a thorough evaluation of HCV-infected patients because of the possibility of extrahepatic manifestations. Antiviral treatment with interferon and ribavirin can be effective and should be considered in patients with neurological complications associated with HCV infection.

  4. Hepatitis C, cryoglobulinemia, and cirrhosis: a meta-analysis.

    PubMed

    Kayali, Zeid; Buckwold, Victor E; Zimmerman, Bridget; Schmidt, Warren N

    2002-10-01

    Approximately 40% of patients with chronic hepatitis C virus (HCV) infection develop detectable serum cryoglobulins or cryoprecipitates (CP), although most do not show clinical or physical signs of syndromic cryoglobulinemia. Although association of HCV with the extrahepatic complications of cryoglobulinemia is widely recognized, the relationship of cryoglobulinemia with liver disease is unclear. We wished to study the relationship between CP and cirrhosis and to determine whether the development of CP is a true covariate for progressive liver disease or a confounding variable that impacts cirrhosis because of patient age, duration of disease, or differences in gender. We undertook a meta-analysis of 19 studies published between 1994 and 2001. The incidence of cirrhosis was compared in patients with and without CP after logistic regression adjustments for accepted risk factors for progressive liver disease, including age, gender, and estimated duration of disease (EDD). A total of 2,323 patients with chronic hepatitis C were identified, with 1,022 (44%) having detectable CP. Cirrhosis was present in 40% of patients with CP but only 17% of patients without CP (total Chi;(2) = 141.69, P <.001). After adjusting for age, gender, and estimated duration of disease by logistic regression, the combined odds ratio for incidence of cirrhosis in patients CP positive versus CP negative was 4.87, (95% CI: 3.32, 7.15), indicating a highly significant association between cirrhosis and cryoglobulinemia. In conclusion, cryoglobulins may be a useful prognostic indicator for increased risk of cirrhosis with chronic hepatitis C.

  5. [Cryoglobulinemia following liver transplantation for cirrhosis secondary to hepatitis C virus infection].

    PubMed

    Argüello Viúdez, L; Bustamante Balén, M; Prieto Castillo, M; Moll Guillén, J L; Ramírez Palanca, J J; Berenguer Lapuerta, J

    1999-02-01

    Hepatitis C virus (HCV) infection has been linked with some extrahepatic immunologic abnormalities. Cryoglobulinemia is one of the most frequently reported. Nevertheless, there are only a few reports of cryoglobulinemia in the setting of liver transplantation. More studies are needed to clarify the frequency of post-OLT cryoglobulinemia in patients with HCV-related cirrhosis and its impact on OLT outcome. A case of a patient who underwent liver transplantation because of HCV end-stage liver disease and in whom cryoglobulinemia appeared 3 years after transplantation is reported. Treatment with cyclophosphamide and steroids was attempted but patient died of septicemia 3 years after liver transplantation.

  6. [Fibrosing alveolitis with hepatitis C-related cryoglobulinemia].

    PubMed

    Witte, L; Rupp, J; Heyer, P; Dalhoff, K; Schaaf, B

    2008-04-01

    A 56-year-old man presented with fever, myalgia and weakness of the limbs for four weeks. The physical examination showed a skin rash, hepatomegaly and reduced mobility of the limbs due to pain. Laboratory tests revealed an elevated rheumatoid factor, cryoglobulins and were positive for hepatitis C-antibodies. The lung function tests indicated mild obstruction and a moderate decrease of diffusion capacity. Bronchoalveolar lavage showed lymphocytic alveolitis. Computed tomography of the thorax revealed mediastinal lymphadenopathy, diffuse ground-glass infiltrates and bilateral signs of fibrosis in the lower lung fields. Because of the fibrosing alveolitis associated with hepatitis C-related cryoglobulinemia, immunosuppression was started with high-dosage prednisone and azathioprine. The symptoms improved on this treatment. Hepatitis C-related cryoglobulinemia is a rare condition that usually presents with nonspecific symptoms. Severe pulmonary involvement is very uncommon. There are no general guidelines about treatment.

  7. Cryoglobulin Test and Cryoglobulinemia Hepatitis C-Virus Related

    PubMed Central

    Gulli, Francesca; Santini, Stefano Angelo; Napodano, Cecilia; Bottoni, Patrizia; Pocino, Krizia; Rapaccini, Gian Ludovico; Basile, Umberto

    2017-01-01

    Cryoglobulins are immunoglobulins that precipitate in serum at temperatures below 37°C and resolubilize upon warming. The clinical syndrome of cryoglobulinemia usually includes purpura, weakness, and arthralgia, but the underlying disease may also contribute other symptoms. Blood samples for cryoglobulin are collected, transported, clotted and spun at 37°C, before the precipitate is allowed to form when serum is stored at 4°C in a Wintrobe tube for at least seven days. The most critical and confounding factor affecting the cryoglobulin test is when the preanalytical phase is not fully completed at 37°C. The easiest way to quantify cryoglobulins is the cryocrit estimate. However, this approach has low accuracy and sensitivity. Furthermore, the precipitate should be resolubilized by warming to confirm that it is truly formed of cryoglobulins. The characterization of cryoglobulins requires the precipitate is several times washed, before performing immunofixation, a technique by which cryoglobulins can be classified depending on the characteristics of the detected immunoglobulins. These features imply a pathogenic role of these molecules which are consequently associated with a wide range of symptoms and manifestations. According to the Brouet classification, Cryoglobulins are grouped into three types by the immunochemical properties of immunoglobulins in the cryoprecipitate. The aim of this paper is to review the major aspects of cryoglobulinemia and the laboratory techniques used to detect and characterize cryoglobulins, taking into consideration the presence and consequences of cryoglobulinemia in Hepatitis C Virus (HCV) infection. PMID:28101312

  8. Cryoglobulin Test and Cryoglobulinemia Hepatitis C-Virus Related.

    PubMed

    Gulli, Francesca; Santini, Stefano Angelo; Napodano, Cecilia; Bottoni, Patrizia; Pocino, Krizia; Rapaccini, Gian Ludovico; Basile, Umberto

    2017-01-01

    Cryoglobulins are immunoglobulins that precipitate in serum at temperatures below 37°C and resolubilize upon warming. The clinical syndrome of cryoglobulinemia usually includes purpura, weakness, and arthralgia, but the underlying disease may also contribute other symptoms. Blood samples for cryoglobulin are collected, transported, clotted and spun at 37°C, before the precipitate is allowed to form when serum is stored at 4°C in a Wintrobe tube for at least seven days. The most critical and confounding factor affecting the cryoglobulin test is when the preanalytical phase is not fully completed at 37°C. The easiest way to quantify cryoglobulins is the cryocrit estimate. However, this approach has low accuracy and sensitivity. Furthermore, the precipitate should be resolubilized by warming to confirm that it is truly formed of cryoglobulins. The characterization of cryoglobulins requires the precipitate is several times washed, before performing immunofixation, a technique by which cryoglobulins can be classified depending on the characteristics of the detected immunoglobulins. These features imply a pathogenic role of these molecules which are consequently associated with a wide range of symptoms and manifestations. According to the Brouet classification, Cryoglobulins are grouped into three types by the immunochemical properties of immunoglobulins in the cryoprecipitate. The aim of this paper is to review the major aspects of cryoglobulinemia and the laboratory techniques used to detect and characterize cryoglobulins, taking into consideration the presence and consequences of cryoglobulinemia in Hepatitis C Virus (HCV) infection.

  9. Mixed Cryoglobulinemia: An Unusual Presentation of Hepatitis C

    PubMed Central

    Mebust, Donald

    2013-01-01

    A 50-year-old man with a history of hepatitis C presented with recurrent episodes of abdominal pain, arthralgia, and weakness. Although these symptoms seemed rather non-specific, a purpuric rash of the lower extremities was the final clue to diagnosis. The diagnosis was then confirmed by histopathologic and serologic testing. PMID:24355899

  10. Persistence

    NASA Astrophysics Data System (ADS)

    Moore, John W.

    1998-11-01

    Eudora Welty, the famous writer, was once asked what should be done by society or government to encourage young writers. Her response, which surprised the questioner, and me when I heard it, was "Nothing". Welty contended that a person who was really a writer would be persistent enough to overcome whatever obstacles were in the way, needing no interference or support from others.

  11. Cryoglobulinemia in Japanese patients with chronic hepatitis C virus infection: host genetic and virological study.

    PubMed

    Nagasaka, A; Takahashi, T; Sasaki, T; Takimoto, K; Miyashita, K; Nakamura, M; Wakahama, O; Nishikawa, S; Higuchi, A

    2001-09-01

    Essential cryoglobulinemia is associated closely with hepatitis C virus (HCV) infection. The mechanism responsible for occurrence of the disease is unclear. The aim of this study was to investigate pathogenetic roles of HCV in cryoglobulinemia. One hundred sixty-seven consecutive patients with HCV were studied clinically by HCV grouping, HCV RNA levels, GBV-C/HGV, HCV quasispecies (target region was hypervariable region-1) and HLA polymorphism. The quasispecies in cryoprecipitate were compared with those in supernatant. The results of HLA polymorphism of patients with cryoglobulinemia were compared with those without cryoglobulinemia and healthy controls. The frequency of HCV-related cryoglobulinemia was 71 of 167 (42.5%). Patients with cirrhosis (36 of 63, 57.1%) had cryoglobulinemia more frequently than those with chronic hepatitis (35 of 104, 33.7%, P < 0.01). No significant differences were not found between the two groups (patients with and without cryoglobulinemia) in age, gender, HCV grouping, HCV RNA level and frequency of GBV-C/HGV. HCV was found quantitatively and clonally more frequently in the cryoprecipitate than in the supernatant. HLA polymorphism presented no significant differences among three groups. The stage of liver disease is one of pathogenetic factors. The greater the presence of HCV quasispecies in cryoprecipitate than in the supernatant indicates that various antigen presentations play an important role in the formation of cryoglobulin, whereas HLA typing dose not seem to contribute to the development of cryoglobulinemia. Copyright 2001 Wiley-Liss, Inc.

  12. Smooth muscle antibodies and cryoglobulinemia are associated with advanced liver fibrosis in Brazilian hepatitis C virus carriers.

    PubMed

    Andrade, Luis Jesuino de Oliveira; Melo, Paulo Roberto Santana de; Atta, Ajax Mercês; Atta, Maria Luiza Brito de Sousa; Jesus, Larissa Santana de; Sousa, Gabriel Menezes de; Silva, Carolina Alves Costa; Paraná, Raymundo

    2011-01-01

    Cryoglobulinemia and non-organ-specific-autoantibody are biomarkers of autoimmunity of the chronic infection caused by hepatitis C virus (HCV). In this work, we report the association between the presence of smooth muscle antibodies (SMA) and cryoglobulinemia and chronic liver disease in HCV carriers. Sixty-five untreated HCV patients, 38 women and 27 men were included in this study. Cryoglobulinemia was tested by cryoprecipitation, SMA by indirect fluorescent antibody test, and liver fibrosis and hepatocellular inflammation activity was investigated by histology of liver biopsy using the METAVIR score. The prevalence of SMA in the patients was 33.8% and cryoglobulinemia was demonstrated in 36.9% patients. Cryoglobulinemia and SMA seropositivity was associated with advanced fibrosis (p < 0.05). The presence of SMA and cryoglobulinemia was not associated with hepatocellular inflammation activity, age, carrier gender or HCV genotype. We concluded that liver biopsy should be recommended for HCV carriers that are seropositive for SMA or cryoglobulinemia.

  13. Persistence of Metal-rich Particles Downstream Zones of Acid Drainage Mixing in Andean Rivers

    NASA Astrophysics Data System (ADS)

    Pasten, P.; Montecinos, M.; Guerra, P. A.; Bonilla, C. A.; Escauriaza, C. R.; Dabrin, A.; Coquery, M.

    2016-12-01

    The Andes mountain range provides the setting for watersheds with high natural background of metals and for mining operations that enhance contaminant mobilization, notably in Northern and Central Chile. Dissolved and solid metal species are actively transported by streams to the Pacific Ocean from area and point sources, like acid drainage. We examine the response of metal rich particle suspensions downstream zones of mixing where shifts in the chemical environment occur. We propose a conceptual model which is used to analyze the fate of copper in the upper Mapocho watershed. The main source of copper is the Yerba Loca river, a naturally impacted stream with pH ranging from 3 to 7 and high concentrations of Cu (0.8 - 6.3 mg/L), Al (1.3 - 7.6 mg/L) and Fe (0.4 - 4.2 mg/L). Steep chemical shifts occur after the confluences with the San Francisco and the Molina rivers. We characterized stream chemistry, hydrological variables and suspended particles, including particle size distribution (PSD), turbidity, and total suspended solids. A marked seasonal behavior was observed, with a higher total Cu flux during smelting periods and a shift towards the dissolved phase during summer. When acid drainage is discharged into a receiving stream, incomplete mixing occurs thereby promoting the formation of a range of metal-rich solids with a characteristic PSD. Similarly, areas of chemical heterogeneity control the partition of metals associated to suspended geomaterials coming from bank and slope erosion. A highly dynamic process ensues where metastable phases shift to new equilibria as fully mixed conditions are reached. Depending on the reaction kinetics, some particles persist despite being exposed to thermodynamically unfavorable chemical environments. The persistence of metal-rich particles downstream zones of acid drainage mixing is important because it ultimately controls the flux of metals being delivered to the ocean by watersheds impacted by acid drainage. Funding from

  14. Hepatitis C virus infection, type III cryoglobulinemia, and necrotizing vasculitis.

    PubMed

    Brownell, Isaac; Fangman, William

    2007-01-27

    A 53-year-old man with chronic hepatitis-C virus infection presented with livedo reticularis, purpura, and leg ulcers. A skin biopsy specimen showed a necrotizing vasculitis. The skin biopsy specimen and serology confirmed the diagnosis of type-III cryoglobulinemia. Bone marrow and peripheral blood showed proliferation of atypical CD5-positive B cells that included a monoclonal population. There is growing evidence that chronic hepatitis-C infection can result in immune dysregulation and expansion of autoimmune B cells that produce cryoglobulins.

  15. Persistent dopants and phase segregation in organolead mixed-halide perovskites

    SciTech Connect

    Rosales, Bryan A.; Men, Long; Cady, Sarah D.; Hanrahan, Michael P.; Rossini, Aaron J.; Vela, Javier

    2016-07-25

    Organolead mixed-halide perovskites such as CH3NH3PbX3–aX'a (X, X' = I, Br, Cl) are interesting semiconductors because of their low cost, high photovoltaic power conversion efficiencies, enhanced moisture stability, and band gap tunability. Using a combination of optical absorption spectroscopy, powder X-ray diffraction (XRD), and, for the first time, 207Pb solid state nuclear magnetic resonance (ssNMR), we probe the extent of alloying and phase segregation in these materials. Because 207Pb ssNMR chemical shifts are highly sensitive to local coordination and electronic structure, and vary linearly with halogen electronegativity and band gap, this technique can provide the true chemical speciation and composition of organolead mixed-halide perovskites. We specifically investigate samples made by three different preparative methods: solution phase synthesis, thermal annealing, and solid phase synthesis. 207Pb ssNMR reveals that nonstoichiometric dopants and semicrystalline phases are prevalent in samples made by solution phase synthesis. We show that these nanodomains are persistent after thermal annealing up to 200 °C. Further, a novel solid phase synthesis that starts from the parent, single-halide perovskites can suppress phase segregation but not the formation of dopants. Our observations are consistent with the presence of miscibility gaps and spontaneous spinodal decomposition of the mixed-halide perovskites at room temperature. This underscores how strongly different synthetic procedures impact the nanostructuring and composition of organolead halide perovskites. In conclusion, better optoelectronic properties and improved device stability and performance may be achieved through careful manipulation of the different phases and nanodomains present in these materials.

  16. Persistent dopants and phase segregation in organolead mixed-halide perovskites

    DOE PAGES

    Rosales, Bryan A.; Men, Long; Cady, Sarah D.; ...

    2016-07-25

    Organolead mixed-halide perovskites such as CH3NH3PbX3–aX'a (X, X' = I, Br, Cl) are interesting semiconductors because of their low cost, high photovoltaic power conversion efficiencies, enhanced moisture stability, and band gap tunability. Using a combination of optical absorption spectroscopy, powder X-ray diffraction (XRD), and, for the first time, 207Pb solid state nuclear magnetic resonance (ssNMR), we probe the extent of alloying and phase segregation in these materials. Because 207Pb ssNMR chemical shifts are highly sensitive to local coordination and electronic structure, and vary linearly with halogen electronegativity and band gap, this technique can provide the true chemical speciation and compositionmore » of organolead mixed-halide perovskites. We specifically investigate samples made by three different preparative methods: solution phase synthesis, thermal annealing, and solid phase synthesis. 207Pb ssNMR reveals that nonstoichiometric dopants and semicrystalline phases are prevalent in samples made by solution phase synthesis. We show that these nanodomains are persistent after thermal annealing up to 200 °C. Further, a novel solid phase synthesis that starts from the parent, single-halide perovskites can suppress phase segregation but not the formation of dopants. Our observations are consistent with the presence of miscibility gaps and spontaneous spinodal decomposition of the mixed-halide perovskites at room temperature. This underscores how strongly different synthetic procedures impact the nanostructuring and composition of organolead halide perovskites. In conclusion, better optoelectronic properties and improved device stability and performance may be achieved through careful manipulation of the different phases and nanodomains present in these materials.« less

  17. Persistent dopants and phase segregation in organolead mixed-halide perovskites

    SciTech Connect

    Rosales, Bryan A.; Men, Long; Cady, Sarah D.; Hanrahan, Michael P.; Rossini, Aaron J.; Vela, Javier

    2016-07-25

    Organolead mixed-halide perovskites such as CH3NH3PbX3–aX'a (X, X' = I, Br, Cl) are interesting semiconductors because of their low cost, high photovoltaic power conversion efficiencies, enhanced moisture stability, and band gap tunability. Using a combination of optical absorption spectroscopy, powder X-ray diffraction (XRD), and, for the first time, 207Pb solid state nuclear magnetic resonance (ssNMR), we probe the extent of alloying and phase segregation in these materials. Because 207Pb ssNMR chemical shifts are highly sensitive to local coordination and electronic structure, and vary linearly with halogen electronegativity and band gap, this technique can provide the true chemical speciation and composition of organolead mixed-halide perovskites. We specifically investigate samples made by three different preparative methods: solution phase synthesis, thermal annealing, and solid phase synthesis. 207Pb ssNMR reveals that nonstoichiometric dopants and semicrystalline phases are prevalent in samples made by solution phase synthesis. We show that these nanodomains are persistent after thermal annealing up to 200 °C. Further, a novel solid phase synthesis that starts from the parent, single-halide perovskites can suppress phase segregation but not the formation of dopants. Our observations are consistent with the presence of miscibility gaps and spontaneous spinodal decomposition of the mixed-halide perovskites at room temperature. This underscores how strongly different synthetic procedures impact the nanostructuring and composition of organolead halide perovskites. In conclusion, better optoelectronic properties and improved device stability and performance may be achieved through careful manipulation of the different phases and nanodomains present in these materials.

  18. Natural DNA mixed with trehalose persists in B-form double-stranding even in the dry state.

    PubMed

    Zhu, Bo; Furuki, Takao; Okuda, Takashi; Sakurai, Minoru

    2007-05-24

    Desiccated calf-thymus DNA has been found to persist in the B-form double-stranding when mixed with trehalose. The stabilization effect on natural DNA depends on the trehalose content, and should basically arise from its ability to tightly hydrogen bond to phosphate groups of DNA, which leads to screening of the large phosphate-phosphate repulsion.

  19. Hepatitis C virus (HCV)-related cryoglobulinemia after liver transplantation for HCV cirrhosis.

    PubMed

    Duvoux, Christophe; Tran Ngoc, Anh; Intrator, Liliane; Hézode, Christophe; Germanidis, Georgios; Pawlotsky, Jean-Michel; Cherqui, Daniel; Dhumeaux, Daniel

    2002-01-01

    The aim of this study was to analyze the clinical impact of hepatitis C virus (HCV)-related cryoglobulinemia in patients that had received liver transplants after HCV cirrhosis. Thirty patients who had received transplants between 1990 and 1996 for HCV cirrhosis and who had a follow-up longer than 1 year were studied. Serum HCV RNA levels, HCV genotype, cryoglobulinemia, rheumatoid factor, serum C3 and C4, IgA, IgG, IgM levels, liver tests, and liver histology were studied 30 +/- 16 months post-transplant. Cryoglobulinemia was found in 9 of 30 patients (30.0%) and was symptomatic in 4 of the 9 cases (glomerulonephritis, 1 case; palpable purpura, 3 cases). Age, sex distribution, alanine aminotransferase (ALAT) activity, and Knodell score did not differ, whether cryoglobulinemia was present or not. Rheumatoid factor (209.5 +/- 70.4 IU/l vs 12.0 +/- 4.4 IU/l, P = 0.004) and IgM levels (3.2 +/- 0.5 g/l vs 1.6 +/- 0.9 g/l, P = 0.0001) were significantly higher, and C4 levels (0.16 +/- 0.16 g/l vs 0.30 +/- 0.10 g/l, P = 0.009) were significantly lower in patients with cryoglobulinemia. One patient died from cryoglobulin-related renal failure. We concluded that, after liver transplantation (LT) for HCV cirrhosis, cryoglobulinemia was frequent and often symptomatic. Cryoglobulinemia did not seem to be associated with more severe graft damage. Cryoglobulinemia-associated morbidity must be taken into account in the management of post-transplant HCV infection.

  20. Role of CXCL10 in cryoglobulinemia.

    PubMed

    Mazzi, Valeria; Ferrari, Silvia Martina; Giuggioli, Dilia; Antonelli, Alessandro; Ferri, Clodoveo; Fallahi, Poupak

    2015-01-01

    Interferon (IFN)-γ-induced protein 10 (IP-10/CXCL10) and its receptor, C-X-C motif receptor 3, appear to contribute to the pathogenesis of hepatitis C virus (HCV)-related mixed cryoglobulinaemia (MC) (HCV+MC). The secretion of CXCL10 by cluster of differentiation (CD) CD4+, CD8+, and natural killer-T cells is dependent on IFN-γ, which is itself mediated by the interleukin-12 cytokine family. Under the influence of IFN-γ, CXCL10 is secreted by several cell types including lymphocytes, hepatocytes, endothelial cells, fibroblasts, etc. In tissues, recruited T helper 1 lymphocytes may be responsible for enhanced IFN-γ and tumour necrosis factor-α production, which in turn stimulates CXCL10 secretion from the cells, therefore creating an amplification feedback loop, and perpetuating the autoimmune process. High levels of CXCL10 in circulation have been found in HCV+MC, especially in patients with clinically active vasculitis. Furthermore, HCV+MC patients with autoimmune thyroiditis (AT) have higher levels than those without AT. Further studies are needed to investigate interactions between chemokines and cytokines in the pathogenesis, and to evaluate whether CXCL10 is a novel therapeutic target in HCV-related MC.

  1. Mixed-matrix membranes incorporated with porous shape-persistent organic cages for gas separation.

    PubMed

    Mao, Hongchao; Zhang, Suobo

    2017-03-15

    There has been much recent interest in the use of porous materials derived from self-assembling, shape-persistent organic cages due to their solubility and easy post-synthetic modification. Herein we report the preparation of novel mixed-matrix membranes (MMMs) employing the porous organic cage Noria and its derivatives Noria-Boc and Noria-CO(t)Bu as the fillers, and a fluorine containing polyimide, 6FDA-DAM, as the polymeric matrix. The physical structures and properties of Noria and its derivatives were measured and investigated. Noria with substituents of Boc (cleaved by thermal treatment during the process of membrane fabrication) and CO(t)Bu groups tend to show much better compatibility with polyimide than Noria itself, resulting in homogeneous dispersion of nanoaggregates and fine adhesion between the two phases in the derived Noria/6FDA-DAM and Noria-CO(t)Bu/6FDA-DAM MMMs. Gas permeation tests revealed that Noria and Noria-CO(t)Bu nanoparticles have different effect on gas separation performance of MMMs. The introduction of Noria into 6FDA-DAM tends to enhance CO2/CH4 selectivity and thus improve its gas separation properties, though a decrease in the observed permeability could be observed. In contrast, the introduction of Noria-CO(t)Bu with higher surface area and larger pores tends to increase the free volume and gas permeability of MMMs. These results show that both the morphology and the gas separation properties of MMMs could be tuned by tailoring the structures of porous organic cages.

  2. Cryoglobulinemia-related vasculitis during effective anti-HCV treatment with PEG-interferon alfa-2b.

    PubMed

    De Blasi, T; Aguilar Marucco, D; Cariti, G; Maiello, A; De Rosa, F G; Di Perri, G

    2008-06-01

    HCV infection may be related to many extrahepatic manifestations including mixed cryoglobulinemia (MC). Clinical manifestations commonly associated to MC include arthralgia, purpura, vasculitis, peripheral neuropathy and renal function abnormalities. Treatment with interferon often leads to remission, especially in virological responders, or to disappearance of MC-related clinical manifestations. We report on a patient with chronic hepatitis C, deficit of G6P-DH, type II MC, who developed a cryoglobulinemic vasculitis with purpura, renal impairment and arterial hypertension, during treatment with PEG-interferon a-2b plus amantadine. The occurrence of purpuric lesions and MC-related nephropathy with increased cryocrit despite negative viremia, in a patient previously asymptomatic, during interferon treatment, is unusual.

  3. Cryoglobulinemia in chronic hepatitis C: clinical aspects and response to treatment with interferon alpha and ribavirin.

    PubMed

    Parise, Edison Roberto; de Oliveira, Ana Cláudia; Ferraz, Maria Lúcia; Pereira, Aparecido Bernardo; Leite, Kátia Ramos

    2007-01-01

    The main extra-hepatic manifestation of hepatitis C is mixed cryoglobulinemia (MC). The aim of this study was to evaluate its prevalence among patients with chronic hepatitis C (CHC), to correlate its presence to host and virological variables and to the response to combined therapy with interferon-alpha and ribavirin. 202 CHC naive patients (136 with chronic hepatitis and 66 with cirrhosis) were consecutively evaluated for the presence of cryoglobulins. Cryoprecipitates were characterized by immunoelectrophoresis and classified according to the Brouet's criteria. The prevalence of MC was 27% (54/202), and 24% of them (13/54) showed major clinical manifestation of the disease. Even though type III MC was more frequent (78%), symptomatic MC was more common in type II MC. The presence of cirrhosis (RR=2.073; IC95%=1.029-4.179; p=0.041), and age of the patients (RR=1.035; IC95%=1.008-1.062; p=0.01) were independently associated with the presence of cryoglobulins. No relationship was found with viral load and genotype. 102 patients were treated with interferon alpha and ribavirin. Among these, 31 had MC. Sustained virological response (around 30%) was similar in patients with and without MC (p=0.971). MC represents a prevalent complication in patients with CHC, specially older and cirrhotic patients. Only 24% of these patients show clinical manifestation of the disease, specially those with type II MC. The presence of MC did not affect the response to therapy.

  4. Textbook Forum. Thermodynamics of "Mixing" of Ideal Gases: A Persistent Pitfall.

    ERIC Educational Resources Information Center

    Meyer, Edwin F.

    1987-01-01

    Discusses some of the misconceptions commonly held suggesting that mixing ideal gases causes an increase in entropy. Argues that the combining processes and resulting total pressure have absolutely nothing to do with the mixing itself. (TW)

  5. Is interleukin-8 an additional to histopathological changes diagnostic marker in HCV-infected patients with cryoglobulinemia?

    PubMed

    Cielecka-Kuszyk, Joanna; Siennicka, Joanna; Jabłońska, Joanna; Rek, Olga; Godzik, Paulina; Rabczenko, Daniel; Madaliński, Kazimierz

    2011-12-01

    The aim of this study was to analyze histopathological changes in the liver and serum inflammatory cytokine level in hepatitis C virus (HCV)-infected patients with and without cryoglobulinemia. The study group consisted of 34 patients with chronic hepatitis C, confirmed by serological and virological markers. Ten out of 34 patients had cryoglobulinemia. The control group consisted of 21 healthy persons. Liver biopsy specimens of HCV-infected patients were evaluated by light microscopy using the grade and the stage according to Batts and Ludwig classification. The quantitative measurements of IL-1β, IL-6, IL-8, IL-10, IL-12p70, and tumor necrosis factor in sera were performed by flow cytometry. The mean age of HCV-infected patients with cryoglobulinemia was higher than age of HCV-infected patients without cryoglobulinemia. Microscopic examination of liver biopsy specimens revealed necroinflammatory activity slightly more prominent in patients with cryoglobulinemia. The most prominent inflammatory changes connected with abundant lymphoid aggregates in most of the examined portal tracts and piecemeal necroses were diagnosed in patients with several extrahepatic manifestations, such as cutaneous manifestations, nephrotic syndrome, polyneuropathy, and arthropathy. Liver fibrosis was similar in patients with and without cryoglobulinemia. The serum levels of all proinflammatory cytokines, especially IL-8, were significantly higher in the patients with cryoglobulinemia in comparison with the patients without cryoglobulinemia and healthy persons. All microscopic features did not correlate with the level of any investigated proinflammatory cytokines.

  6. Persistent Müllerian duct syndrome of mixed anatomical variant (combined male and female type) with mixed germ cell tumor of left intra-abdominal testis.

    PubMed

    Mohapatra, Manisha; Subramanya, Yerraguntla Sarma

    2016-01-01

    Persistent Müllerian duct syndrome (PMDS) is a rare form of internal male pseudohermaphroditism characterized by retention of Müllerian duct derivatives in a phenotypically and karyotypically male patient. Deficiency of anti-Müllerian hormone (AMH) secretion or resistance to AMH action due to defective AMH-II receptor is presumed to cause such syndrome in the majority of cases. About 158 PMDS cases have been reported so far, out of which 31 cases are associated with testicular neoplasms. Herein, we describe an interesting case of young male initially diagnosed and treated for inguinal hernia, but finally diagnosed as "PMDS of mixed anatomical variant (combined male and female type) with mixed germ cell tumor of left intra-abdominal testis" comprising components of seminoma and yolk sac tumor and treated successfully.

  7. The Federal Transformation Intervention Model in Persistently Lowest Achieving High Schools: A Mixed-Methods Study

    ERIC Educational Resources Information Center

    Le Patner, Michelle B.

    2012-01-01

    This study examined the American Recovery and Reinvestment Act federal mandate of the Transformation Intervention Model (TIM) outlined by the School Improvement Grant, which was designed to turn around persistently lowest achieving schools. The study was conducted in four high schools in a large Southern California urban district that selected the…

  8. Mixed infections with Chlamydia and porcine epidemic diarrhea virus - a new in vitro model of chlamydial persistence

    PubMed Central

    2010-01-01

    Background Chlamydiae induce persistent infections, which have been associated with a wide range of chronic diseases in humans and animals. Mixed infections with Chlamydia and porcine epidemic diarrhea virus (PEDV) may result in generation of persistent chlamydial infections. To test this hypothesis, an in vitro model of dual infection with cell culture-adapted PEDV and Chlamydia abortus or Chlamydia pecorum in Vero cells was established. Results Infected cultures were investigated by immunofluorescence (IF), transmission electron microscopy (TEM) and re-infection experiments. By IF, Chlamydia-infected cells showed normal inclusions after 39 hpi. Dual infections with Chlamydia abortus revealed a heterogenous mix of inclusion types including small inclusions consisting of aberrant bodies (ABs), medium-sized inclusions consisting of ABs and reticulate bodies and normal inclusions. Only aberrant inclusions were observable in dual infection experiments with Chlamydia pecorum and PEDV. TEM examinations of mixed infections with Chlamydia abortus and Chlamydia pecorum revealed aberrant chlamydial inclusions containing reticulate-like, pleomorphic ABs, which were up to 2 μm in diameter. No re-differentiation into elementary bodies (EBs) was detected. In re-infection experiments, co-infected cells produced fewer EBs than monoinfected cells. Conclusions In the present study we confirm that PEDV co-infection alters the developmental cycle of member species of the family Chlamydiaceae, in a similar manner to other well-described persistence induction methods. Interestingly, this effect appears to be partially species-specific as Chlamydia pecorum appears more sensitive to PEDV co-infection than Chlamydia abortus, as evidenced by TEM and IF observations of a homogenous population of aberrant inclusions in PEDV - Chlamydia pecorum co-infections. PMID:20663197

  9. Determining WRF Boundary Layer and Land Surface Parameterizations to Simulate Surface Fluxes for Pollutant Mixing During Persistent Cold Air Pools

    NASA Astrophysics Data System (ADS)

    Holmes, H.; Trail, M.

    2016-12-01

    During the night stable atmospheric boundary layers, associated with shallow boundary layer heights and decreased turbulent mixing, lead to an increase in air pollution concentrations. This is common in mountainous terrain, where cold air pools (CAPs) form during the night, and in the wintertime can exist throughout the day and last for weeks; a phenomenon known as a persistent CAP. During persistent CAP events, particulate matter concentrations in the atmosphere accumulate and reach levels that are harmful to human health. While atmospheric models are able to capture the synoptic processes associated with CAP formation and destruction, the models do not adequately simulate the microscale processes near the earth's surface. Therefore impacting predictions of surface-atmosphere exchange, including the turbulent mixing and accumulation of pollutants in the atmospheric boundary layer. Specifically, surface fluxes and turbulence intensity are overestimated during CAP events, which leads to an underprediction in pollutant concentrations. This presentation will present results from a Weather Research and Forecasting (WRF) sensitivity analysis where simulated surface fluxes are compared to observations collected in the Salt Lake Valley, Utah. The turbulence and surface flux observations are from a previously published study, which found a correlation between decreased turbulent mixing and increased pollutant concentrations during wintertime persistent CAPs. Hourly momentum, latent heat, and sensible heat fluxes from WRF are evaluated using observations. Different land surface models (LSM) and planetary boundary layer (PBL) parameterizations significantly impact the WRF surface flux results but have less of a difference on estimates of surface wind speed, temperature, and mixing ratio. Results are shown for four LSM/PBL configurations and indicate that the sensible heat flux is overestimated by a factor of 2-3 during the daytime for persistent CAPs, and the latent heat

  10. Mixed germ cell tumor after bilateral orchidopexy in persistent Müllerian duct syndrome with transverse testicular ectopia.

    PubMed

    Manassero, Francesca; Cuttano, Maria Giuseppa; Morelli, Girolamo; Salinitri, Giuseppe; Spurio, Michela; Selli, Cesare

    2004-01-01

    The persistent müllerian duct syndrome is characterized by the retention of müllerian derivatives (fallopian tubes, uterus) in patients otherwise normally virilized, usually with cryptorchidism or an inguinal hernia. Very rarely, this syndrome is associated with transverse testicular ectopia, which designates the condition when both testes descend through the same inguinal canal into the same scrotal sac. We report on a patient with both conditions, who had T1N2M0 scrotal mixed germ cell tumor of the testis (teratoma and embryonal carcinoma), 18 years after bilateral orchidopexy. The literature concerning this uncommon association is reviewed.

  11. Effect of growth conditions and substratum composition on the persistence of coliforms in mixed-population biofilms.

    PubMed Central

    Camper, A K; Jones, W L; Hayes, J T

    1996-01-01

    Laboratory reactors operated under oligotrophic conditions were used to evaluate the importance of initial growth rate and substratum composition on the long-term persistence of coliforms in mixed-population biofilms. The inoculum growth rate had a dramatic effect on the ability of coliforms to remain on surfaces. The most slowly grown coliforms (mu = 0.05/h) survived at the highest cell concentration. Antibody staining revealed that Klebsiella pneumoniae existed primarily as discrete microcolonies on the surface. Both coliforms and heterotrophic plate count bacteria were supported in larger numbers on a reactive substratum, mild steel, than on polycarbonate. PMID:8899991

  12. An Unusual Case of HCV Negative Cryoglobulinemia Presenting as Symmetrical Peripheral Gangrene

    PubMed Central

    Meher, Lalit Kumar; Behera, Samir Kumar; Nayak, Sachidananda; Tripathy, Sujit Kumar

    2016-01-01

    Cryoglobulins are monoclonal or polyclonal immunoglobulins that undergo reversible precipitation at low temperatures. Cryoglobulinemia is associated with HCV infection in more than 90% cases, the remaining 10% being called as Essential Cryoglobulinemia which is generally associated with a severe course and suboptimal response to conventional therapies. As the digital vessels are more prone to colder temperatures, hyperviscosity in those vessels can initiate local thrombosis and may manifest as ischemic ulceration and gangrene. We report here a very unusual case of HCV negative cryoglobulinemic vasculitis presenting as symmetrical peripheral gangrene of fingers and toes. PMID:27190872

  13. Mixing by thermal convection in a spherical shell and the persistence of mantle reservoirs

    NASA Astrophysics Data System (ADS)

    Kellogg, L. H.; Heien, E. M.

    2013-12-01

    Understanding the dynamics of mixing in the mantle is fundamental to understanding the origins of the isotopic heterogeneity observed in oceanic islands and at mid-ocean ridges. The mantle is homogenized by convection, as the stretching and folding common to all kinematic mixing disperses heterogeneity. Mid-ocean ridges exhibit a degree of global homogeneity (while also showing some long-lived heterogeneity on all scales.) Oceanic islands indicate sources that have been distinct from the MORB source for a significant fraction of Earth's history. Thus it has long been a goal of computational geodynamics to understand the factors controlling the rate and efficacy of mantle mixing. The time and spatial scales of mixing are influenced by the kinematics of flow, plate motion, viscosity variations, compositional heterogeneity, and phase transitions. Chaotic mixing is observed in time-varying 2-D flows; by contrast, the factors controlling mixing in 3-D remain somewhat poorly understood. We test the use of a new mantle convection code, ASPECT, to investigate mixing in convection in 2-D annulus and in a 3-D spherical shell. ASPECT is an adaptive mesh finite element code based on the Deal.II library and developed and distributed by the Computational Infrastructure for Geodynamics (CIG). We run a suite of models at various Rayleigh numbers. Each model runs long enough to eliminate any transient behavior associated with our choice of initial conditions; when the model achieves a quasi-steady state, we introduce massless, passive tracer particles to enable visualization of mixing. The particles are tracked over time as they disperse, allowing the use of quantitative measures of mixing such as the Lyapunov exponent and configurational entropy. Stirring may be rapid on a regional scale, while heterogeneities at the global scale are retained because of isolation across long-wavelength cells. Essentially, the regions that exhibit high rates of stretching and thinning have the most

  14. Type II cryoglobulinemia is not associated with hepatitis C infection: the Dutch experience.

    PubMed

    Tervaert, J W Cohen; Van Paassen, P; Damoiseaux, J

    2007-06-01

    Mixed cryoglobulinemia (MC) are cryoprecipitable immunocomplexes. In type II MC, a combination of polyclonal and monoclonal immunoglobulins is found, whereas in type III a combination of polyclonal immunoglobulins is detected. MC is usually associated with hepatitis C (HCV) infection as has been found in studies that have been performed in countries with a high prevalence of HCV. Because HCV has an extremely low prevalence in the Netherlands (<0.1% of the population), we wondered whether HCV is also associated with MC in our regional referral center. To answer this question, we tested consecutive patients with type II MC for HCV antibodies and for HCV-mRNA by polymerase chain reaction (PCR). Between January 2000 and June 2005, 22 patients tested positive for type II MC. Seven patients had essential MC, 2 patients had MC due to a lymphoproliferative disease, 10 patients had MC in the context of a systemic autoimmune disease, and 3 patients had MC without a clear diagnosis. HCV antibodies were not detected in any of the 22 patients. Also, all samples tested negative for HCV-mRNA. During follow-up none of these patients developed an HCV infection. In summary, the estimated occurrence of HCV in 60-90% of patients with MC is not found in our region where MC is only infrequently associated with HCV. In a substantial proportion of our patients a really "essential MC" is observed. A search for yet unknown etiological factors is clearly needed in these patients, who frequently have severe renal involvement warranting aggressive immunosuppressive therapy.

  15. Systemic sclerosis and cryoglobulinemia: our experience with overlapping syndrome of scleroderma and severe cryoglobulinemic vasculitis and review of the literature.

    PubMed

    Giuggioli, Dilia; Manfredi, Andreina; Colaci, Michele; Manzini, Carlo Umberto; Antonelli, Alessandro; Ferri, Clodoveo

    2013-09-01

    Systemic sclerosis (SSc) is an immune-mediated disorder characterized by multiple organ fibrotic alterations and diffuse microangiopathy. The SSc can be associated with other connective tissue diseases and less frequently with systemic vasculitides, including cryoglobulinemic vasculitis (CV). The aim of the present study was to investigate the prevalence of CV in a large series of SSc patients. The presence of serum cryoglobulins was detected in 246 SSc patients (24 M and 222 F, age 61±13.5 SD years, disease duration 9.3±6.7 SD years); the observed clinico-serological findings, in particular the presence of SSc-CV overlapping syndrome, were carefully analyzed and compared with previous data reported in the literature. The presence of circulating cryoglobulins was found in 7/246 (2.8%) of SSc patients; namely, 2 subjects only trace amounts of cryoglobulins, while 5 (2%) showed mixed cryoglobulinemia (type II, IgG-IgMk), low C4, rheumatoid factor seropositivity, and hepatitis C virus infection. Among SSc patients with serum mixed cryoglobulins, 4 (1.6%) developed a clinically overt CV, while the other one was totally asymptomatic with regard to typical vasculitic manifestations. Patients with SSc-CV overlapping syndrome had limited cutaneous SSc with serum anticentromere antibodies, pulmonary hypertension, clinico-serological features of HCV-related CV, and non-healing skin ulcers of the lower limbs. In all cases, the diagnosis of SSc preceded the clinical onset of CV, from 3 to 17years. The treatment with rituximab was useful on skin ulcers of lower limb in 2/3 patients; however, the overall clinical outcome of the four SSc-CV patients was unusually severe: one with very severe skin ulcers complicated by gangrene required bilateral through-the knee amputation, the other three subjects died because of severe heart failure, and in two cases because of untreatable pulmonary hypertension. In the literature, the prevalence of mixed cryoglobulinemia in scleroderma

  16. Coronary artery bypass grafting in a patient with active idiopathic cryoglobulinemia: revisiting the issue

    PubMed Central

    Fakih, Hafiz Abdul Moiz; Elueze, Emmanuel; Vij, Rajiv

    2016-01-01

    Background Cryoglobulinemia is a cold-reactive autoimmune disease. It is of distinctive importance in cardiac surgery because of the use of hypothermic cardiopulmonary bypass (CPB). Cryoglobulins, which activate at variable levels of hypothermia, can cause precipitation during surgery leading to possibly severe leukocytoclastic or necrotizing vasculitis, clinically manifested as ischemic events, such as cutaneous ulcerations, glomerulonephritis, arthritis, or peripheral neuropathies among the most reported associated comorbidities. Management of CPB and systemic protection in this rare but unique scenario requires individualized planning. We report the case of a patient with active cryoglobulinemia who was preoperatively managed with plasmapheresis. He underwent hypothermic coronary bypass with no precipitation and flare during and after surgery. Case presentation We describe the case of a 59-year-old Caucasian male with clinically significant idiopathic cryoglobulinemia and history of recurrent skin lesions and toe amputations secondary to cold exposure. He presented with 2-h duration of chest pain and new onset atrial fibrillation. After cardiac catheterization, a diagnosis of three-vessel coronary artery disease was established and coronary artery bypass grafting (CABG) was scheduled. Because of a high risk of flare-up during surgery, the patient was preemptively treated with two sessions of plasmapheresis before bypass. He then underwent hypothermic CABG. The pre- and perioperative course was unremarkable without any clinical evidence of precipitation. The patient was discharged on day 6 postoperatively without any complications. Conclusion Preoperative plasmapheresis before hypothermic coronary bypass can prevent fatal cryoglobulinemia-related complications in patients with active disease. PMID:26908383

  17. The occurrence and persistence of mixed biofilms in automobile air conditioning systems.

    PubMed

    Simmons, R B; Rose, L J; Crow, S A; Ahearn, D G

    1999-09-01

    Twelve automobile air conditioner systems from six manufacturers and three countries, selected mostly because of complaints of unpleasant odors in the passenger compartment, were examined for microbial growth by direct microscopy and enrichment culture. Mixed populations of fungi and bacteria (with occasional protozoa) were observed in biofilms in at least some of the components from all used units. The aluminum heat exchanger fins from ten evaporators demonstrated bacterial biofilms that yielded Methylobacterium mesophilicum. Penicillium viridicatum colonized components from four units. These bacteria and fungi were recoverable repeatedly from these units during 'dry' storage of up to 27 months. This report associates a bacterial-fungal community with disagreeable air quality in some automobiles.

  18. Variable but persistent coexistence of Prochlorococcus ecotypes along temperature gradients in the ocean's surface mixed layer.

    PubMed

    Chandler, Jeremy W; Lin, Yajuan; Gainer, P Jackson; Post, Anton F; Johnson, Zackary I; Zinser, Erik R

    2016-04-01

    The vast majority of the phytoplankton communities in surface mixed layer of the oligotrophic ocean are numerically dominated by one of two ecotypes of Prochlorococcus, eMIT9312 or eMED4. In this study, we surveyed large latitudinal transects in the Atlantic and Pacific Ocean to determine if these ecotypes discretely partition the surface mixed layer niche, or if populations exist as a continuum along key environmental gradients, particularly temperature. Transitions of dominance occurred at approximately 19-21°C, with the eMED4 ecotype dominating the colder, and eMIT9312 ecotype dominating the warmer regions. Within these zones of regional dominance, however, the minority ecotype was not competed to extinction. Rather, a robust log-linear relationship between ecotype ratio and temperature characterized this stabilized coexistence: for every 2.5°C increase in temperature, the eMIT9312:eMED4 ratio increased by an order of magnitude. This relationship was observed in both quantitative polymerase chain reaction and in pyrosequencing assays. Water column stratification also contributed to the ecotype ratio along the basin-scale transects, but to a lesser extent. Finally, instances where the ratio of the eMED4 and eMIT9312 abundances did not correlate well with temperature were identified. Such occurrences are likely due to changes in water temperatures outpacing changes in community structure.

  19. Prevalence and persistence of male DNA identified in mixed saliva samples after intense kissing.

    PubMed

    Kamodyová, Natália; Durdiaková, Jaroslava; Celec, Peter; Sedláčková, Tatiana; Repiská, Gabriela; Sviežená, Barbara; Minárik, Gabriel

    2013-01-01

    Identification of foreign biological material by genetic profiling is widely used in forensic DNA testing in different cases of sexual violence, sexual abuse or sexual harassment. In all these kinds of sexual assaults, the perpetrator could constrain the victim to kissing. The value of the victim's saliva taken after such an assault has not been investigated in the past with currently widely used molecular methods of extremely high sensitivity (e.g. qPCR) and specificity (e.g. multiplex Y-STR PCR). In our study, 12 voluntary pairs were tested at various intervals after intense kissing and saliva samples were taken from the women to assess the presence of male DNA. Sensitivity-focused assays based on the SRY (single-copy gene) and DYS (multi-copy gene) sequence motifs confirmed the presence of male DNA in female saliva after 10 and even 60min after kissing, respectively. For specificity, standard multiplex Y-STR PCR profiling was performed and male DNA was found in female saliva samples, as the entire Y-STR profile, even after 30min in one sample. Our study confirms that foreign DNA tends to persist for a restricted period of time in the victim's mouth, can be isolated from saliva after prompt collection and can be used as a valuable source of evidence. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  20. [Purpura pigmentosa progressiva in type III cryoglobulinemia and tartrazine intolerance. A follow-up over 20 years].

    PubMed

    Kalinke, D U; Wüthrich, B

    1999-01-01

    A 58 year old patient with hepatitis virus C (HCV) infection had a secondary polyclonal IgG-IgM cryoglobulinemia with a benign 20 year course. Clinically the patient suffered from progressive pigmented purpura (PPP). Histologic evaluation revealed a lymphocytic vasculitis. Food containing tartrazine triggered flares of the PPP, as demonstrated with controlled oral provocation testing. In most of the previously described cases of HCV and type III cryoglobulinemia, the typical cutaneous finding was palpable purpura with leukocytoclastic vasculitis.

  1. Persistent small-scale features in maps of the anisotropy of ocean surface velocities--implications for mixing?

    NASA Astrophysics Data System (ADS)

    Sen, A.; Arbic, B. K.; Scott, R. B.; Holland, C. L.; Logan, E.; Qiu, B.

    2006-12-01

    Much of the stirring and mixing in the upper ocean is due to geostrophically balanced mesoscale eddies. Ocean general circulation models commonly parameterize eddy effects. Geostrophic turbulence models show that parameterizations of eddy mixing depend on the isotropy of the eddies. Motivated by this, we investigate the isotropy of oceanic mesoscale eddies with seven years of sea surface height data recorded by satellite altimeters. From these data, we determined a sea surface height anomaly, and surface geostrophic velocities u and v in the zonal (east-west) and meridional (north-south) directions, respectively. From the latter two quantities we can calculate zonal and meridional kinetic energies u2 and v2. Integrals of u2 and v2 around latitude bands 10 degrees wide are nearly equal, in contrast with the results of simple beta-plane geostrophic turbulence models, which suggest that zonal motions should predominate. Maps of the quantity u2-v2 (normalized by standard error) show fine-scale structures that persist over times longer than the lifespan of a turbulent eddy. Thus the mesoscale eddy field is locally anisotropic almost everywhere. Further investigation into the causes of these small-scale structures is needed and is currently underway.

  2. Persistence of Trichinella spiralis in rat carcasses experimentally mixed in different feed.

    PubMed

    Oivanen, L; Mikkonen, T; Haltia, L; Karhula, H; Saloniemi, H; Sukura, A

    2002-01-01

    Trichinella spiralis infected rat carcasses were incubated for 6 weeks in several animal feeds to assess how long Trichinella can present a risk for an outbreak in contaminated feeds. In groups of 6, 24 infected target rats were placed in silage, grained barley, propionic acid-preserved feed, and also into simulated pasture conditions. Test environments were sampled after one-, 2-, 4-, and 6-week-incubations. Trichinella larvae were recovered by digestion, and their infectivity was evaluated in rats. A two-week incubation reduced the number of recovered larvae, but still after 6 weeks low numbers were isolated from all feeds except from the experimental group simulating pasture conditions. After 2 weeks storage, the larvae were infective in all storage environments. However, up to 4 weeks, they survived only in the propionic acid-fermented feed and there in small numbers with reduced reproductive capability. This indicates the possibility of farm animals to get infection from rats or other infected material being hazardously mixed with hay or other feed. If silage is stored for at least one month before use, however, the risk from this forage appears to be minimized.

  3. Persistence of Trichinella spiralis in Rat Carcasses Experimentally Mixed in Different Feed

    PubMed Central

    Oivanen, L; Mikkonen, T; Haltia, L; Karhula, H; Saloniemi, H; Sukura, A

    2002-01-01

    Trichinella spiralis infected rat carcasses were incubated for 6 weeks in several animal feeds to assess how long Trichinella can present a risk for an outbreak in contaminated feeds. In groups of 6, 24 infected target rats were placed in silage, grained barley, propionic acid-preserved feed, and also into simulated pasture conditions. Test environments were sampled after one-, 2-, 4-, and 6-week-incubations. Trichinella larvae were recovered by digestion, and their infectivity was evaluated in rats. A two-week incubation reduced the number of recovered larvae, but still after 6 weeks low numbers were isolated from all feeds except from the experimental group simulating pasture conditions. After 2 weeks storage, the larvae were infective in all storage environments. However, up to 4 weeks, they survived only in the propionic acid-fermented feed and there in small numbers with reduced reproductive capability. This indicates the possibility of farm animals to get infection from rats or other infected material being hazardously mixed with hay or other feed. If silage is stored for at least one month before use, however, the risk from this forage appears to be minimized. PMID:12831173

  4. Persistent tidal mixing fronts as a key habitat feature for the harbour porpoise (Phocoena phocoena)

    NASA Astrophysics Data System (ADS)

    Skov, H.; Heinänen, S.; Sveegaard, S.; Nabe-Nielsen, J.; Thomsen, F.; Zydelis, R.

    2016-02-01

    Despite being the most common cetacean species in European waters and the focal species in relation to management and marine habitat conservation efforts in these waters, a unified understanding of the distribution of harbour porpoise Phocoena phocoena in regions like the North Sea is still beyond reach. This situation has been created by fragmented and uneven survey data, as well as by the lack of dynamic 3-dimensional data on the oceanographic structures characterising the areas most used by the species. In an attempt to generalise distribution patterns in the North Sea on the basis of a large part of existing survey data a new approach has been tested involving dynamic species distribution modelling combined with post-processed data from detailed 3-D flow models. Distribution models (GAMs) were developed from 15-year survey databases to estimate harbour porpoise distributions in the German and British parts of the North Sea. Oceanographic conditions during porpoise surveys were estimated using a high-resolution hydrodynamic model. The stability of the water column described by temperature differences between surface and bottom and eddy activity were the most important dynamic determinants of the density of animals during summer in both parts of the North Sea. The spatial variability of the environmental envelope was estimated by classifying the optimal range of water column stability and eddy activity in each time step of the hydrodynamic model. The resulting time series depicts surprisingly stable regions of optimal oceanographic conditions coinciding with the areas of tidal mixing fronts. The time series of oceanographic envelopes were validated in-situ with positional data from satellite-tracked animals from the period 2004-2014. Our approach demonstrate that pelagic seascape metrics defined as a combination of 3-D oceanographic variables and their spatial gradients calculated at an appropriate spatial scale can resolve a comprehensive understanding of the

  5. [Specific damage to the kidneys in patients with chronic hepatitis C associated with cryoglobulinemia].

    PubMed

    Milovanova, S Iu; Tégaĭ, S V; Russkikh, A V; Kozlovskaia, L V

    2011-01-01

    To reveal clinical and morphological characteristics of renal damage in patients with cryoglobulinemia (CGE) associated with chronic viral hepatitis C (CVH-C) for upgrading diagnosis, prognosis and optimization of the treatment methods. Two groups of CVH-C patients were studied: with CGE (group 1, n = 64) and free of CGE (group 2, n = 62) matched for gender, age and duration of the disease. Biopsy of the liver for assessment of the histological activity index and histological sclerosis index by METAVIR scale was conducted in 63 patients. Of patients with CGE-related damage to the kidneys, 48 were examined for clinical picture with morphological investigation of renal tissue in 15 of them including semiquantitative evaluation of fibrosis degree and activity. Patients with CVH-C and CGE had a wider spectrum of systemic lesions than CVH-C patients without CGE. Only CGE patients demonstrated more severe affection of the skin, joints, kidneys and the nervous system. Therefore, CGE can be considered as a marker of poor prognosis. Liver biopsy showed that CGE patients had more pronounced fibrosis (3-6 points) versus 0-2 points in 80% patients from group 2. Duration of CVH-C from probable infection to renal damage in 48 patients with CGE glomerulonephritis (GN) averaged 197.05 +/- 18.5 months. Renal biopsy diagnosed CGE mesangiocapillary GN in 13 patients and membranoproliferative GN in 2 patients. Patients with HCV infection had a more severe proliferative form of nephritis--mesangiocapillary GN. In 48 GN patients with HCV-infection and CGE, GN ran latently with moderate urinary syndrome in 29 (60.4%) patients, with nephrotic syndrome--in 9 (18.6%), with acute nephritic syndrome--in 10 (21.0%) patients. Most of the patients had arterial hypertension, 13 patients had creatinemia (3.02 +/- 0.55 mg/dl), rapidly progressive GN was diagnosed in 4 patients. Persistent CGE marks poor prognosis in CHC patients and is an indication for antiviral treatment to prevent severe organ

  6. Complexities in Isolation and Purification of Multiple Viruses from Mixed Viral Infections: Viral Interference, Persistence and Exclusion.

    PubMed

    Kumar, Naveen; Barua, Sanjay; Riyesh, Thachamvally; Chaubey, Kundan K; Rawat, Krishan Dutt; Khandelwal, Nitin; Mishra, Anil K; Sharma, Nitika; Chandel, Surender S; Sharma, Shalini; Singh, Manoj K; Sharma, Dinesh K; Singh, Shoor V; Tripathi, Bhupendra N

    2016-01-01

    Successful purification of multiple viruses from mixed infections remains a challenge. In this study, we investigated peste des petits ruminants virus (PPRV) and foot-and-mouth disease virus (FMDV) mixed infection in goats. Rather than in a single cell type, cytopathic effect (CPE) of the virus was observed in cocultured Vero/BHK-21 cells at 6th blind passage (BP). PPRV, but not FMDV could be purified from the virus mixture by plaque assay. Viral RNA (mixture) transfection in BHK-21 cells produced FMDV but not PPRV virions, a strategy which we have successfully employed for the first time to eliminate the negative-stranded RNA virus from the virus mixture. FMDV phenotypes, such as replication competent but noncytolytic, cytolytic but defective in plaque formation and, cytolytic but defective in both plaque formation and standard FMDV genome were observed respectively, at passage level BP8, BP15 and BP19 and hence complicated virus isolation in the cell culture system. Mixed infection was not found to induce any significant antigenic and genetic diversity in both PPRV and FMDV. Further, we for the first time demonstrated the viral interference between PPRV and FMDV. Prior transfection of PPRV RNA, but not Newcastle disease virus (NDV) and rotavirus RNA resulted in reduced FMDV replication in BHK-21 cells suggesting that the PPRV RNA-induced interference was specifically directed against FMDV. On long-term coinfection of some acute pathogenic viruses (all possible combinations of PPRV, FMDV, NDV and buffalopox virus) in Vero cells, in most cases, one of the coinfecting viruses was excluded at passage level 5 suggesting that the long-term coinfection may modify viral persistence. To the best of our knowledge, this is the first documented evidence describing a natural mixed infection of FMDV and PPRV. The study not only provides simple and reliable methodologies for isolation and purification of two epidemiologically and economically important groups of viruses, but

  7. Complexities in Isolation and Purification of Multiple Viruses from Mixed Viral Infections: Viral Interference, Persistence and Exclusion

    PubMed Central

    Kumar, Naveen; Barua, Sanjay; Riyesh, Thachamvally; Chaubey, Kundan K.; Rawat, Krishan Dutt; Khandelwal, Nitin; Mishra, Anil K.; Sharma, Nitika; Chandel, Surender S.; Sharma, Shalini; Singh, Manoj K.; Sharma, Dinesh K.; Singh, Shoor V.; Tripathi, Bhupendra N.

    2016-01-01

    Successful purification of multiple viruses from mixed infections remains a challenge. In this study, we investigated peste des petits ruminants virus (PPRV) and foot-and-mouth disease virus (FMDV) mixed infection in goats. Rather than in a single cell type, cytopathic effect (CPE) of the virus was observed in cocultured Vero/BHK-21 cells at 6th blind passage (BP). PPRV, but not FMDV could be purified from the virus mixture by plaque assay. Viral RNA (mixture) transfection in BHK-21 cells produced FMDV but not PPRV virions, a strategy which we have successfully employed for the first time to eliminate the negative-stranded RNA virus from the virus mixture. FMDV phenotypes, such as replication competent but noncytolytic, cytolytic but defective in plaque formation and, cytolytic but defective in both plaque formation and standard FMDV genome were observed respectively, at passage level BP8, BP15 and BP19 and hence complicated virus isolation in the cell culture system. Mixed infection was not found to induce any significant antigenic and genetic diversity in both PPRV and FMDV. Further, we for the first time demonstrated the viral interference between PPRV and FMDV. Prior transfection of PPRV RNA, but not Newcastle disease virus (NDV) and rotavirus RNA resulted in reduced FMDV replication in BHK-21 cells suggesting that the PPRV RNA-induced interference was specifically directed against FMDV. On long-term coinfection of some acute pathogenic viruses (all possible combinations of PPRV, FMDV, NDV and buffalopox virus) in Vero cells, in most cases, one of the coinfecting viruses was excluded at passage level 5 suggesting that the long-term coinfection may modify viral persistence. To the best of our knowledge, this is the first documented evidence describing a natural mixed infection of FMDV and PPRV. The study not only provides simple and reliable methodologies for isolation and purification of two epidemiologically and economically important groups of viruses, but

  8. Efficacy and Safety of Sofosbuvir Plus Daclatasvir for Treatment of HCV-Associated Cryoglobulinemia Vasculitis.

    PubMed

    Saadoun, David; Pol, Stanislas; Ferfar, Yasmina; Alric, Laurent; Hezode, Christophe; Si Ahmed, Si Nafa; de Saint Martin, Luc; Comarmond, Cloé; Bouyer, Anne Sophie; Musset, Lucile; Poynard, Thierry; Resche Rigon, Matthieu; Cacoub, Patrice

    2017-07-01

    Circulating mixed cryoglobulins are detected in 40%-60% of patients with hepatitis C virus (HCV) infection, and overt cryoglobulinemia vasculitis (CryoVas) develops in approximately 15% of patients. Remission of vasculitis has been associated with viral clearance, but few studies have reported the effectiveness of direct-acting antiviral drugs in these patients. We performed an open-label, prospective, multicenter study of the effectiveness and tolerance of an all-oral, interferon- and ribavirin-free regimen of sofosbuvir plus daclatasvir in patients with HCV-associated CryoVas. Forty-one consecutive patients with active HCV-associated CryoVas (median age, 56 y; 53.6% women) were recruited from hospitals in Paris, France, from 2014 through 2016. They received sofosbuvir (400 mg/day) plus daclatasvir (60 mg/day) for 12 weeks (n = 32) or 24 weeks (n = 9), and were evaluated every 4 weeks until week 24 and at week 36. Blood samples were analyzed for complete blood count, serum chemistry profile, level of alanine aminotransferase, rheumatoid factor activity, C4 fraction of complement, and cryoglobulin; peripheral blood mononuclear cells were isolated for flow cytometry analysis. Thirty-seven patients (90.2%) had a complete clinical response (defined by improvement of all the affected organs involved at baseline and no clinical relapse) after a median time of 12 weeks of therapy; all had a sustained virologic response (no detectable serum HCV RNA 12 weeks after the end of antiviral therapy). Patients' mean cryoglobulin level decreased from 0.56 ± 0.18 at baseline to 0.21 ± 0.14 g/L at week 36, and no cryoglobulin was detected in 50% of patients at this time point. After antiviral therapy, patients had increased numbers of T-regulatory cells, IgM+CD21-/low-memory B cells, CD4+CXCR5+ interleukin 21+ cells, and T-helper 17 cells, compared with before therapy. After a median follow-up period of 26 months (interquartile range, 20-30 mo), no patients had a serious adverse

  9. Prevalence of cryoglobulinemia and autoimmunity markers in renal-transplant patients.

    PubMed

    Faguer, S; Kamar, N; Boulestin, A; Esposito, L; Durand, D; Blancher, A; Rostaing, L

    2008-04-01

    To examine the prevalence of cryoglobulinemia (Cryo) and autoimmune markers in renal-transplant recipients in a stable condition, and to determine its risk factors and impact upon allograft function. In May, 2006, 117 kidney-transplant (KT) recipients, aged 31 â 76 years, were tested for cryoglobulinemia, hepatitis B and C, complement C3, C4, CH50, antinuclear (ANAs), anticytoplasmic nuclear (ANCAs) and anticardiolipid antibodies, rheumatoid factor (RF), and lymphocyte subpopulations. Renal, liver, and hematological tests were also performed. Immunosuppressive regimens were based on calcineurin inhibitors (82%). Cryo was positive in 47 patients (Cryo(+): 40.2%), of whom 13 were HCV+ (27.7%), with characteristics of Type II in 21.2% and Type III in 78.8%. Cryo was positive in 13/16 (81.2%) of HCV+/RNA+ patients vs. 34/101 (33.6%, p = 0.0003) of HCV-negative patients. Cryo(+) RT patients had been recipients of a graft for longer (142 months) than Cryo(-) patients, i.e., 95 months (p = 0.02). Creatinine clearances were similar in the two groups (56 vs. 50 ml/mn, p = 0.5), as were microalbuminuria and albuminemia. There was no difference between Cryo(-) and Cryo(+) patients in terms of age, sex, HLA mismatch, daily steroid doses, liver and hematological tests, ANAs, anticardiolipid antibodies, serum complement, and lymphocyte subpopulations. RF occurred in all Cryo(+) patients and in 82.8% of Cryo(-) patients, with higher titers in the Cryo(+) group (23 vs. 9 UI/ml, p = 0.012). ANCA occurred in nine Cryo(-) but in no Cryo(+) patients (p = 0.013). Finally, a multivariate analysis was not able to determine any predictive factor associated with cryoglobulinemia. Cryoglobulinemia is frequent after KT, and is associated with HCV markers, RF, and absence of ANCA.

  10. Inflammation biomarkers in chronic hepatitis C: association with liver histopathology, HCV genotype and cryoglobulinemia.

    PubMed

    Atta, Maria; Cabral, Milena; Santos, Gilvan; Paraná, Raymundo; Atta, Ajax

    2012-10-01

    This work investigated the profile of inflammation biomarkers in patients with chronic hepatitis C and its association with liver fibrosis, hepatic necroinflammatory activity, viral genotypes and cryoglobulinemia. Seventy-eight untreated patients were studied. Biomarker levels were determined by immunoassays, cryoglobulinemia by cryoprecipitation and liver histopathology investigated using METAVIR scores. Decreased levels of α(1)-acid glycoprotein (AGP), C3 and haptoglobin (Hp) were observed in the patients (P < 0.0001). Increased α(1)-antitrypsin (P < 0.01) and ferritin (P < 0.0001) levels were found in this group, but C-reactive protein (CRP) and C4 levels were unaltered. Alanine aminotransferase inversely correlated with Hp (P < 0.01) and AGP (P = 0.01), whereas it was directly correlated with ferritin (P < 0.05) and AGP (P < 0.0001). The levels of CRP, C3 and C4 were lower in the patients with hepatic necroinflammatory activity (P < 0.05). Patients with advanced fibrosis had low levels of Hp and AGP (P < 0.05 and P < 0.01, respectively). Neither infection with different viral genotypes nor cryoglobulinemia caused an alteration in biomarker levels. Chronic hepatitis C virus infection alters the levels of some biomarkers, which are mainly observed in patients with liver fibrosis and hepatic necroinflammatory activity.

  11. Persistence of insecticides in ready-mix formulations and their efficacy against Lipaphis erysimi (Kalt) in cauliflower.

    PubMed

    Gupta, Suman; Sharma, R K; Gajbhiye, V T; Gupta, R K

    2013-03-01

    Persistence of cypermethrin, deltamethrin, profenofos, and triazophos in cauliflower curd was studied, following application of two premix formulations viz: Roket 44EC (profenofos 40 % + cypermethrin 4 %) and Anaconda Plus 36EC (triazophos 35 % + deltamethrin 1 %) at recommended (1.0 L ha(-1)) and double doses (2.0 L ha(-1)). In the case of Roket 44EC, residues of cypermethrin dissipated with the half-life values of 1.5-2.1 days, whereas residues of profenofos dissipated with the half-life of 2.9-3.3 days on cauliflower curd. In the case of Anaconda, residues of triazophos and deltamethrin dissipated from curd with the half-life values of 2.6-3.0 and 2.2-2.6 days, respectively. Both the combination mix significantly reduced the aphid population up to 14 days after spray and increased the yield by 155-160 % over control. Anaconda (2.0 L ha(-1)) treated plots yielded the highest number of marketable curds. Based on risk assessment analysis, safe waiting period of 3 and 5 days has been suggested for Roket 44EC and Anaconda Plus 36EC, respectively, in cauliflower at recommended dose of application.

  12. Prevalence of cryoglobulinemia in chronic hepatitis C virus infection and response to treatment with interferon-alpha.

    PubMed

    Akriviadis, E A; Xanthakis, I; Navrozidou, C; Papadopoulos, A

    1997-12-01

    Chronic hepatitis C virus (HCV) infection is associated with a variety of clinically important extrahepatic abnormalities. We have assessed the prevalence of cryoglobulinemia and of the clinical syndrome associated with it in patients with chronic HCV infection. We also have evaluated the clinical, serologic, and biochemical response to antiviral treatment with interferon-alpha (IFN-alpha). Eighty-one patients with chronic liver disease associated with HCV infection were included. Cryoglobulins were sought in the serum. All patients were examined carefully for clinical manifestations of cryoglobulinemia (e.g., palpable purpura, Raynaud's syndrome, arthritis, peripheral neuropathy, Sjögren's syndrome, glomerulonephritis). Antiviral treatment with IFN-alpha, at a dose of 3 to 5 million units, 3 times weekly, was given to 20 patients with cryoglobulinemia. Cryoglobulins were detected in 45.7% of patients. Signs and symptoms of the clinical syndrome associated with cryoglobulinemia were present in 12.3% of the entire group of patients (27% of the subgroup with detectable cryoglobulins). Patients with cryoglobulinemia were older (mean age, 56 +/- 15 vs. 44 +/- 16 years; p = 0.002) and had a higher rate of cirrhosis (48.6% vs. 18.2%, rate ratio = 4.26, 95% confidence interval = 2.11 to 8.58, p = 0.00005) compared to patients without cryoglobulinemia. Cryoglobulins disappeared from the serum in 13 (65%) of the 20 patients who were treated for 6 to 12 months with IFN-alpha. This effect was affiliated in most patients with resolution of the clinical findings associated with cryoglobulinemia and return of transaminases to normal levels. Recurrence of cryoglobulinemia was observed in two thirds of the patients who were observed after treatment with IFN-alpha. We conclude that cryoglobulins are present in 45.7% of patients with chronic HCV infection. Symptoms or signs or both associated with the presence of cryoglobulins develop in a high proportion (27%) of these patients

  13. Hematologic malignancies in patients with cryoglobulinemia: association with autoimmune and chronic viral diseases.

    PubMed

    Trejo, Olga; Ramos-Casals, Manuel; López-Guillermo, Armando; García-Carrasco, Mario; Yagüe, Jordi; Cervera, Ricard; Font, Josep; Ingelmo, Miguel

    2003-08-01

    To determine the prevalence and clinical characteristics of hematologic malignancies occurring in a large series of patients diagnosed with cryoglobulinemia, and to study their association and overlap with autoimmune and/or chronic viral diseases. We retrospectively analyzed the occurrence of hematologic malignancies in 607 patients diagnosed with cryoglobulinemia in a single institution. Clinical, histologic, and serologic characteristics of patients were recorded on a protocol form. Hematologic malignancies were diagnosed according to the Revised European-American Lymphoma/World Health Organization classification criteria. Of the total cohort of 607 patients with cryoglobulinemia, we retrospectively identified 27 patients (5%) in whom a hematologic malignancy was diagnosed, including 24 (89%) lymphoproliferative and 3 (11%) myeloid malignancies. Fifteen (56%) were men and 12 (44%) women, with a median age at diagnosis of hematologic malignancy of 67 years (range, 44 to 88 years). The identified hematologic malignancies were non-Hodgkin lymphoma (n = 18), Hodgkin lymphoma (n = 2), chronic lymphocytic leukemia (n = 2), and 1 case each of multiple myeloma, Waldenström macroglobulinemia, Castleman disease, chronic myeloid leukemia and myelodysplastic syndrome. Of the 18 patients with non-Hodgkin lymphoma, there was a predilection for specific histologic types (diffuse large B-cell lymphoma in 8 cases and small lymphocytic lymphoma in 4) and a higher frequency of a primary extranodal origin in 6 (33%) cases. Conditions associated with hematologic malignancies were hepatitis C virus (HCV) infection in 14 patients (52%) and systemic autoimmune diseases in 13 (48%), with both HCV and systemic autoimmune disease in 6 cases (22%). Hematologic neoplasia associated with cryoglobulinemia is defined by a clear predominance of lymphoproliferative disorders (mainly non-Hodgkin lymphoma), with substantial extranodal involvement and an elevated presence of immunologic markers

  14. Genetic predispositions for the presence of cryoglobulinemia and serum autoantibodies in Chinese patients with chronic hepatitis C.

    PubMed

    Hwang, S-J; Chu, C-W; Huang, D-F; Lan, K-H; Chang, F-Y; Lee, S-D

    2002-01-01

    Chronic hepatitis C virus (HCV) infection may induce immunological disorders in the host such as the presence of cryoglobulinemia or serum autoantibodies. The pathogenesis of these phenomena remains unclear but may reflect the host's genetic predispositions. The aim of this study was to evaluate the association between these immunological manifestations and human leukocyte antigen (HLA) expression in Chinese patients with chronic hepatitis C. The presence of serum cryoglobulin and autoantibodies (antinuclear antibody, antismooth muscle antibody, antimitochondrial antibody, antiliver-kidney-microsomal antibody) was determined in 122 Chinese patients with chronic hepatitis C. HLA class I and class II antigens were measured by microlymphocytotoxicity assay or by DNA typing in 122 chronic hepatitis C patients and 228 healthy controls. Of the 122 patients with chronic hepatitis C, 52 (43%) had cryoglobulinemia and 48 (39%) had serum autoantibodies. A significant difference in HLA frequency was noted for DR3, which was found in 36.5% of patients with cryoglobulinemia compared with 8.6% of patients without cryoglobulinemia and 11.3% of healthy controls. A significant difference in HLA frequency was also noted for DR4, which was found in 45.8% of patients with serum autoantibodies compared with 17.6% of patients without serum autoantibodies and 19% of healthy controls. Our results suggest the existence of HLA-linked susceptibility genes (DR3 or DR4) for the development of cryoglobulinemia or serum autoantibodies in Chinese patients with chronic hepatitis C.

  15. Clinical, neurophysiological, and skin biopsy findings in peripheral neuropathy associated with hepatitis C virus-related cryoglobulinemia.

    PubMed

    Biasiotta, A; Casato, M; La Cesa, S; Colantuono, S; Di Stefano, G; Leone, C; Carlesimo, M; Piroso, S; Cruccu, G; Truini, A

    2014-04-01

    Hepatitis C virus (HCV)-related cryoglobulinemia commonly causes disabling complications including peripheral neuropathy and neuropathic pain. In this prospective clinical, neurophysiological, and skin biopsy study we aimed at assessing clinical characteristics and risk factors of peripheral neuropathy and neuropathic pain in patients with HCV-related cryoglobulinemia. We enrolled 69 consecutive patients with HCV-related cryoglobulinemia. We diagnosed neuropathic pain with the DN4 (Neuropathic Pain Diagnostic) questionnaire, and rated the various neuropathic pains with the Neuropathic Pain Symptom Inventory (NPSI). All patients underwent a standard nerve conduction study to assess Aβ-fiber function, laser-evoked potentials to assess Aδ-fiber function, and skin biopsy to assess C-fiber terminals. Of the 69 patients studied, 47 had a peripheral neuropathy, and 29 had neuropathic pain. Patients with peripheral neuropathy were older than those without (P < 0.0001). While peripheral neuropathy was significantly associated with the duration of HCV infection (P < 0.01), it was unrelated to the duration of cryoglobulinemia and cryocrit (P > 0.5). The severity of peripheral neuropathy significantly correlated with the duration of HCV infection (P < 0.05). Laser-evoked potential amplitudes were significantly lower in patients with than in those without neuropathic pain (P < 0.05). Conversely, no difference was found in nerve conduction study and skin biopsy findings (P > 0.05). Our findings show that peripheral neuropathy is related to age and HCV infection, rather than to cryoglobulinemia, and neuropathic pain is associated with damage to nociceptive pathways as assessed with laser-evoked potentials; this might be useful for designing more effective clinical interventions for these common HCV related-cryoglobulinemia complications.

  16. Cold hard facts of cryoglobulinemia: updates on clinical features and treatment advances.

    PubMed

    Ghetie, Daniela; Mehraban, Navid; Sibley, Cailin H

    2015-01-01

    Cryoglobulins are immunoglobulins that precipitate at temperatures less than 37°C. They occur secondary to infectious, autoimmune, and malignant processes. In the Brouet classification, type I cryoglobulinemia is caused by hyperviscosity, whereas type II and III manifestations are caused by vasculitis in target organs (primarily skin, peripheral nerves, and kidney). New classification criteria were recently proposed that may help with study and treatment of cryoglobulinemic vasculitis (CryoVas). Hepatitis C virus is the most common cause of CryoVas and treatment with antivirals can be curative in mild cases, whereas rituximab is highly effective in treating active vasculitis in more severe cases.

  17. Hepatitis C virus-associated cryoglobulinemia with membrano-proliferative glomerulonephritis treated with prednisolone and interferon: A case report.

    PubMed

    Guo, Qiao-Yan; Wu, Man; Wang, Yang-Wei; Sun, Guang-Dong

    2017-08-01

    Hepatitis C virus (HCV) is a major cause of liver-associated morbidity and has an increasing prevalence worldwide. Hepatitis C virus infection may lead to chronic hepatitis, cirrhosis and liver failure. However, it is also associated with a wide range of extra-hepatic complications, such as cryoglobulinemia, an immune complex disease associated with cryoglobulin leading to multiple organ damage and, while the major symptom is vasculitis. The present study reported on a-58-year-old woman who was diagnosed with HCV-associated cryoglobulinemia with skin, kidney and blood system damage and biopsy-proven cryoglobulinemia membrano-proliferative glomerulonephritis. HCV RNA clearance occurred within a few weeks of interferon treatment and the patient was then treated by prednisolone and sustained interferon. While the therapeutic effect was obvious at first, the disease reappeared in combination with refractory infection and multiple organ failure, and the patient finally died. HCV-associated cryoglobulinemia is uncommon in developing countries such as China, while treatment guidelines remain to be established, particularly if complex complications are present.

  18. Hepatitis C virus-associated cryoglobulinemia with membrano-proliferative glomerulonephritis treated with prednisolone and interferon: A case report

    PubMed Central

    Guo, Qiao-Yan; Wu, Man; Wang, Yang-Wei; Sun, Guang-Dong

    2017-01-01

    Hepatitis C virus (HCV) is a major cause of liver-associated morbidity and has an increasing prevalence worldwide. Hepatitis C virus infection may lead to chronic hepatitis, cirrhosis and liver failure. However, it is also associated with a wide range of extra-hepatic complications, such as cryoglobulinemia, an immune complex disease associated with cryoglobulin leading to multiple organ damage and, while the major symptom is vasculitis. The present study reported on a-58-year-old woman who was diagnosed with HCV-associated cryoglobulinemia with skin, kidney and blood system damage and biopsy-proven cryoglobulinemia membrano-proliferative glomerulonephritis. HCV RNA clearance occurred within a few weeks of interferon treatment and the patient was then treated by prednisolone and sustained interferon. While the therapeutic effect was obvious at first, the disease reappeared in combination with refractory infection and multiple organ failure, and the patient finally died. HCV-associated cryoglobulinemia is uncommon in developing countries such as China, while treatment guidelines remain to be established, particularly if complex complications are present. PMID:28810602

  19. [Anti LKM-1 antibodies and cryoglobulinemia in autoimmune chronic hepatitis and virus C hepatitis].

    PubMed

    Jirón, M I; Ardiles, A; Parra, M A; Orellana, J

    2000-03-01

    Anti liver kidney microsome antibodies (LKM-1) have been recently incorporated to the study and classification of chronic autoimmune hepatitis (HC-A1). The presence of anti LKM-1 antibodies and essential cryoglobulinemia is frequent in virus C associated chronic hepatitis (HC-VC). To study the frequency of anti LKM-1 antibodies and cryoglobulin levels in patients with HC-AI, HC-VC and cryptogenic cirrhosis. Forty-two patients were studied. Nineteen adult women with classic HC-AI with positive antinuclear or anti smooth muscle antibodies. Five patients of less than 20 years old with HC-AI and negative antinuclear and anti smooth muscle antibodies. Ten adult women with cryptogenic cirrhosis, 4 women and 4 men with HC-VC. Serum samples were obtained at 37 degrees C. Antinuclear, anti smooth muscle and anti LKM-1 antibodies were measured by indirect immunofluorescence using Hep-2 cells and rat tissue slices as substrates. Cryoglobulins were determined by the traditional method and cryocrit. All studied patients were anti LKM-1 negative. All had significant circulating cryoglobulin levels. In this sample of patients with HC-AI or HC-VC, anti LKM-1 antibodies were not detected but all had cryoglobulinemia.

  20. Policy and Persistence: An Exploratory Mixed Methods Case Study of "Last Mile" Students at Portland State University

    ERIC Educational Resources Information Center

    Wubbold, Joseph Mark

    2012-01-01

    In an extension of educational attainment research, this exploratory mixed- methods case study examines the influence of institutional policies on the behavior of five cohorts (n = 925) of traditional first time, full time (FTFT) freshmen--called "Last Mile" students--at one urban research university located in the Pacific Northwest.…

  1. Policy and Persistence: An Exploratory Mixed Methods Case Study of "Last Mile" Students at Portland State University

    ERIC Educational Resources Information Center

    Wubbold, Joseph Mark

    2012-01-01

    In an extension of educational attainment research, this exploratory mixed- methods case study examines the influence of institutional policies on the behavior of five cohorts (n = 925) of traditional first time, full time (FTFT) freshmen--called "Last Mile" students--at one urban research university located in the Pacific Northwest.…

  2. Weed Establishment and Persistence after Water Pipeline Installation and Reclamation in the Mixed Grass Prairie of Western North Dakota

    USDA-ARS?s Scientific Manuscript database

    In the northern mixed grass prairie, the dominant native vegetation type is a stable perennial grass community. Increasing human activity in western North Dakota in combination with propagule availability from historic agricultural activity may lead to greater incidence of prairie colonization by no...

  3. Hepatitis C virus (HCV)-related cryoglobulinemia: cryoglobulin type and anti-HCV profile.

    PubMed

    Minopetrou, Martha; Hadziyannis, Emilia; Deutsch, Melanie; Tampaki, Maria; Georgiadou, Asimina; Dimopoulou, Eleni; Vassilopoulos, Dimitrios; Koskinas, John

    2013-05-01

    Cryoglobulin characteristics in chronic hepatitis C (CHC) might be of importance for knowing more about the pathogenesis and treatment of the disease. We aimed to investigate the relationship between cryoglobulin types and their specificity against hepatitis C virus (HCV) antigenic epitopes in CHC patients. We analyzed samples from 43 patients with HCV-associated cryoglobulinemia, of whom 4 had concomitant lymphoma. Cryoglobulins were measured, purified, typed by immunofixation electrophoresis, and tested for IgG and IgM anti-HCV antibodies by immunoblot analysis and an enzyme-linked immunosorbent assay (ELISA). Clinical and other laboratory data were recorded. The median cryocrit level of the tested samples was 6%. Type I cryoglobulins were detected in 9.3% (4/43) of the cryoprecipitates, and type II cryoglobulins were detected in 48.8% (21/43) of the cryoprecipitates. IgM monoclonal protein, mainly IgM(κ), was found in 92% (23/25) of type I and II cryoprecipitates. Type III cryoglobulins were identified in 41.9% (18/43) of the patients and were associated with high blood serum IgG levels. In 81.3% (13/16) of type II and 92.3% (12/13) of type III cryoglobulins, there was IgG reactivity against the viral core region. Ninety-two percent and 32% of IgG anti-HCV core-positive cryoprecipitates had additional specificities against the NS3 and NS4 regions, respectively. Also, IgM anti-HCV antibodies were detected in 31% of the cryoprecipitates. In conclusion, all types of cryoglobulins were found in patients with HCV-associated cryoglobulinemia, with type II being the most frequently identified. Type III cryoglobulins were common and were associated with high serum IgG levels. HCV-related cryoglobulins demonstrated IgM, and particularly IgG, anti-HCV specificities, mainly against the core and NS3 epitopes.

  4. Hepatitis C Virus (HCV)-Related Cryoglobulinemia: Cryoglobulin Type and Anti-HCV Profile

    PubMed Central

    Minopetrou, Martha; Deutsch, Melanie; Tampaki, Maria; Georgiadou, Asimina; Dimopoulou, Eleni; Vassilopoulos, Dimitrios; Koskinas, John

    2013-01-01

    Cryoglobulin characteristics in chronic hepatitis C (CHC) might be of importance for knowing more about the pathogenesis and treatment of the disease. We aimed to investigate the relationship between cryoglobulin types and their specificity against hepatitis C virus (HCV) antigenic epitopes in CHC patients. We analyzed samples from 43 patients with HCV-associated cryoglobulinemia, of whom 4 had concomitant lymphoma. Cryoglobulins were measured, purified, typed by immunofixation electrophoresis, and tested for IgG and IgM anti-HCV antibodies by immunoblot analysis and an enzyme-linked immunosorbent assay (ELISA). Clinical and other laboratory data were recorded. The median cryocrit level of the tested samples was 6%. Type I cryoglobulins were detected in 9.3% (4/43) of the cryoprecipitates, and type II cryoglobulins were detected in 48.8% (21/43) of the cryoprecipitates. IgM monoclonal protein, mainly IgM(κ), was found in 92% (23/25) of type I and II cryoprecipitates. Type III cryoglobulins were identified in 41.9% (18/43) of the patients and were associated with high blood serum IgG levels. In 81.3% (13/16) of type II and 92.3% (12/13) of type III cryoglobulins, there was IgG reactivity against the viral core region. Ninety-two percent and 32% of IgG anti-HCV core-positive cryoprecipitates had additional specificities against the NS3 and NS4 regions, respectively. Also, IgM anti-HCV antibodies were detected in 31% of the cryoprecipitates. In conclusion, all types of cryoglobulins were found in patients with HCV-associated cryoglobulinemia, with type II being the most frequently identified. Type III cryoglobulins were common and were associated with high serum IgG levels. HCV-related cryoglobulins demonstrated IgM, and particularly IgG, anti-HCV specificities, mainly against the core and NS3 epitopes. PMID:23467778

  5. Paradoxical persistence through mixed-system dynamics: towards a unified perspective of reversal behaviours in evolutionary ecology.

    PubMed

    Williams, Paul David; Hastings, Alan

    2011-05-07

    Counterintuitive dynamics of various biological phenomena occur when composite system dynamics differ qualitatively from that of their component systems. Such composite systems typically arise when modelling situations with time-varying biotic or abiotic conditions, and examples range from metapopulation dynamics to population genetic models. These biological, and related physical, phenomena can often be modelled as simple financial games, wherein capital is gained and lost through gambling. Such games have been developed and used as heuristic devices to elucidate the processes at work in generating seemingly paradoxical outcomes across a spectrum of disciplines, albeit in a field-specific, ad hoc fashion. Here, we propose that studying these simple games can provide a much deeper understanding of the fundamental principles governing paradoxical behaviours in models from a diversity of topics in evolution and ecology in which fluctuating environmental effects, whether deterministic or stochastic, are an essential aspect of the phenomenon of interest. Of particular note, we find that, for a broad class of models, the ecological concept of equilibrium reactivity provides an intuitive necessary condition that must be satisfied in order for environmental variability to promote population persistence. We contend that further investigations along these lines promise to unify aspects of the study of a range of topics, bringing questions from genetics, species persistence and coexistence and the evolution of bet-hedging strategies, under a common theoretical purview.

  6. Paradoxical persistence through mixed-system dynamics: towards a unified perspective of reversal behaviours in evolutionary ecology

    PubMed Central

    Williams, Paul David; Hastings, Alan

    2011-01-01

    Counterintuitive dynamics of various biological phenomena occur when composite system dynamics differ qualitatively from that of their component systems. Such composite systems typically arise when modelling situations with time-varying biotic or abiotic conditions, and examples range from metapopulation dynamics to population genetic models. These biological, and related physical, phenomena can often be modelled as simple financial games, wherein capital is gained and lost through gambling. Such games have been developed and used as heuristic devices to elucidate the processes at work in generating seemingly paradoxical outcomes across a spectrum of disciplines, albeit in a field-specific, ad hoc fashion. Here, we propose that studying these simple games can provide a much deeper understanding of the fundamental principles governing paradoxical behaviours in models from a diversity of topics in evolution and ecology in which fluctuating environmental effects, whether deterministic or stochastic, are an essential aspect of the phenomenon of interest. Of particular note, we find that, for a broad class of models, the ecological concept of equilibrium reactivity provides an intuitive necessary condition that must be satisfied in order for environmental variability to promote population persistence. We contend that further investigations along these lines promise to unify aspects of the study of a range of topics, bringing questions from genetics, species persistence and coexistence and the evolution of bet-hedging strategies, under a common theoretical purview. PMID:21270032

  7. Hepatitis C eradication and improvement of cryoglobulinemia-associated rash and membranoproliferative glomerulonephritis with interferon and ribavirin after kidney transplantation

    PubMed Central

    Zeman, Marilyn; Campbell, Patricia; Bain, Vincent G

    2006-01-01

    Postrenal transplant hepatitis C is increasing in frequency due to the high prevalence of hepatitis C among patients with renal failure. Despite this, there is still no standard hepatitis C treatment available for renal transplanted recipients. Combination antiviral hepatitis C therapy, the standard of care in the nontransplant population, is generally avoided because of documented renal graft rejection secondary to interferon treatment. A case of a male patient with postrenal transplant hepatitis C, which was associated with cryoglobulinemia and glomerulonephritis of the graft, is presented. He was treated with standard interferon with ribavirin. Sustained viral clearance was achieved despite ongoing evidence of cryoglobulinemia. Renal function, which had been deteriorating before treatment, improved as evidenced by the stabilization of serum creatinine and marked improvement of proteinuria. In conclusion, in selected patients, combination antiviral therapy may still be a viable option postrenal transplant. PMID:16779461

  8. Persistence of host-associated Bacteroidales gene markers and their quantitative detection in an urban and agricultural mixed prairie watershed.

    PubMed

    Tambalo, Dinah D; Fremaux, Bastien; Boa, Tyler; Yost, Christopher K

    2012-06-01

    Microbial source tracking is an emerging tool developed to protect water sources from faecal pollution. In this study, we evaluated the suitability of real time-quantitative PCR (qPCR) Taqman assays developed for detection of host-associated Bacteroidales markers in a prairie watershed. The qPCR primers and probes used in this study exhibited high accuracy (88-96% sensitivity and ≥ 99% host specificity) in detecting Bacteroidales spp. that are associated with faeces from humans, ruminants, bovines, and horses. The ruminant- and human-associated markers were also found in high concentrations within individual faecal samples, ranging from 3.4 to 7.3 log(10) marker copy numberg(-1) of individual host faeces. Following validation of host sensitivity and specificity, the host-associated Bacteroidales markers were detected in the Qu'Appelle Valley watershed of Saskatchewan, Canada which experiences a diversity of anthropogenic inputs. Concentrations of the ruminant marker were well-correlated with proximity to cattle operations and there was a correlation between the marker and Escherichia coli concentrations at these sites. Low concentrations of the human faecal marker were measured throughout the sampling sites, and may indicate a consistent influx of human faecal pollution into the watershed area. Persistence of each of the Bacteroidales host-associated marker was also studied in situ. The results indicated that the markers persist for shorter periods of time (99% decay in <8 days) compared with the conventional E. coli marker (99% decay in >15 days), suggesting they are effective at detecting recent faecal contamination events. The levels of Bacteroidales markers and E. coli counts did not correlate with the presence of the pathogenic bacteria, Salmonella spp. or Campylobacter spp. detected in the Qu'Appelle Valley. Collectively, the results obtained in this study demonstrated that the qPCR approach for detecting host-associated Bacteroidales spp. markers can be a

  9. Long-term mass transfer and mixing-controlled reactions of a DNAPL plume from persistent residuals

    NASA Astrophysics Data System (ADS)

    Liu, Yuan; Illangasekare, Tissa H.; Kitanidis, Peter K.

    2014-02-01

    Understanding and being able to predict the long-term behavior of DNAPL (i.e., PCE and TCE) residuals after active remediation has ceased have become increasingly important as attention at many sites turns from aggressive remediation to monitored natural attenuation and long-term stewardship. However, plume behavior due to mass loading and reactions during these later phases is less studied as they involve large spatial and temporal scales. We apply both theoretical analysis and pore-scale simulations to investigate mass transfer from DNAPL residuals and subsequent reactions within the generated plume, and, in particular, to show the differences between early- and late-time behaviors of the plume. In the zone of entry of the DNAPL entrapment zone where the concentration boundary layer in the flowing groundwater has not fully developed, the pore-scale simulations confirm the past findings based on laboratory studies that the mass transfer increases as a power-law function of the Peclét number, and is enhanced due to reactions in the plume. Away from the entry zone and further down gradient, the long-term reactions are limited by the available additive and mixing in the porous medium, thereby behave considerably differently from the entry zone. For the reaction between the contaminant and an additive with intrinsic second-order bimolecular kinetics, the late-time reaction demonstrates a first-order decay macroscopically with respect to the mass of the limiting additive, not with respect to that of the contaminant. The late-time decay rate only depends on the intrinsic reaction rate and the solubility of the entrapped DNAPL. At the intermediate time, the additive decays exponentially with the square of time (t2), instead of time (t). Moreover, the intermediate decay rate also depends on the initial conditions, the spatial distribution of DNAPL residuals, and the effective dispersion coefficient.

  10. Delineation of autoantibody repertoire through differential proteogenomics in hepatitis C virus-induced cryoglobulinemia

    PubMed Central

    Ogishi, Masato; Yotsuyanagi, Hiroshi; Moriya, Kyoji; Koike, Kazuhiko

    2016-01-01

    Antibodies cross-reactive to pathogens and autoantigens are considered pivotal in both infection control and accompanying autoimmunity. However, the pathogenic roles of autoantibodies largely remain elusive without a priori knowledge of disease-specific autoantigens. Here, through a novel quantitative proteogenomics approach, we demonstrated a successful identification of immunoglobulin variable heavy chain (VH) sequences highly enriched in pathological immune complex from clinical specimens obtained from a patient with hepatitis C virus-induced cryoglobulinemia (HCV-CG). Reconstructed single-domain antibodies were reactive to both HCV antigens and potentially liver-derived human proteins. Moreover, over the course of antiviral therapy, a substantial “de-evolution” of a distinct sub-repertoire was discovered, to which proteomically identified cryoprecipitation-prone autoantibodies belonged. This sub-repertoire was characterized by IGHJ6*03-derived, long, hydrophobic complementarity determining region (CDR-H3). This study provides a proof-of-concept of de novo mining of autoantibodies and corresponding autoantigen candidates in a disease-specific context in human, thus facilitating future reverse-translational research for the discovery of novel biomarkers and the development of antigen-specific immunotherapy against various autoantibody-related disorders. PMID:27403724

  11. Causes of death in symptomatic cryoglobulinemia: 30 years of observation in a Department of Internal Medicine.

    PubMed

    Saccardo, E; Novati, P; Sironi, D; Castelnovo, L; Rinaldi, G; Monti, G

    2007-09-01

    Cryoglobulinemic Syn&come (CS) is a multi-systemic disease, and its fatal evolution can involve different organs. To describe the most frequent causes of death in CS, by researching different evolutions between older cases and those of the last 15 years. The data of 238 patients affected by symptomatic cryoglobulinemia followed by our Medicine Department in the last 30 years are recorded in a database. 54 are presently living and being followed, 70 (36F, 34M) have died. The type II/type III ratio is 5/4. We distinguish between two groups, the oldest, without any data on HCV, and the most recent who were tested for HCV. The follow-up ranges from 0.5 to 16 years. Liver diseases (25 cases, 9 with hepatic carcinomas), lymphomas and myeloproliferative diseases (12), and cardiovascular events (8) are the most reported causes of death. Sepsis, neurological syndromes, nephropathy, other malignancies and diffuse vasculitis are also reported. The median age at death was 67.2 years (58.4 in the oldest group, 71.9 in the other). Hepatic carcinomas are reported only after 1991. Cirrhosis complications are more frequent in patients affected by HCV. The increase in instrumental diagnostic ability and the improved survival of patients with cirrhosis account for the increase in patients with hepatic carcinomas. Improved treatment has resulted in a reduction of deaths from renal failure.

  12. Quantifying loading, toxic concentrations, and systemic persistence of chloride in a contemporary mixed-land-use watershed using an experimental watershed approach.

    PubMed

    Hubbart, J A; Kellner, E; Hooper, L W; Zeiger, S

    2017-03-01

    A nested-scale experimental watershed study was implemented to quantify loading and persistence of chloride in an urbanizing, mixed-land-use watershed. A Midwest USA (Missouri) watershed was partitioned into five sub-basins with contrasting dominant land use. Streamwater was tested for chloride concentration four days per week from October 2009 through May 2014 at each site. Monitoring sites included co-located gauging and climate stations recording variables at 30-minute intervals. Results indicate significant (p<0.01) differences in chloride concentrations and loading between sites. Loading consistently increased from the forested headwaters (average=507kgday(-1)) to primarily urban watershed terminus (average=7501kgday(-1)). Chloride concentrations were highest (average=83.9mgL(-1)) with the greatest frequency of acutely toxic conditions (i.e. 860mgL(-1)) mid-watershed. This finding is in-part attributable to the ratio of chloride application to streamflow volume (i.e. increasing flow volume with stream distance resulted in chloride dilution, offsetting increased percent urban land use with stream distance). Results highlight the important, yet often confounding, interactions between pollutant loading and flow dynamics. Chloride peaks occurred during late winter/early spring melting periods, implicating road salt application as the primary contributor to the chloride regime. Floodplain groundwater analysis indicated seasonal sink/source relationships between the stream and floodplain, which could contribute to chronic toxicity and persistent low Cl(-) concentrations in streamwater year-round. Results hold important implications for resource managers wishing to mitigate water quality and aquatic habitat degradation, and suggest important water quality limitations to stream restoration success in complex urban aquatic ecosystems. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Chronic hepatitis C virus infection: Prevalence of extrahepatic manifestations and association with cryoglobulinemia in Bulgarian patients

    PubMed Central

    Stefanova-Petrova, Diana V; Tzvetanska, Anelia H; Naumova, Elisaveta J; Mihailova, Anastasia P; Hadjiev, Evgenii A; Dikova, Rumiana P; Vukov, Mircho I; Tchernev, Konstantin G

    2007-01-01

    AIM: To assess the prevalence of extrahepatic manifestations in Bulgarian patients with chronic hepatitis C virus (HCV) infection and identify the clinical and biological manifestations associated with cryoglobulinemia. METHODS: The medical records of 136 chronically infected HCV patients were reviewed to assess the prevalence of extrahepatic manifestations. Association between cryoglobulin-positivity and other manifestations were identified using χ2 and Fisher’s exact test. Risk factors for the presence of extrahepatic manifestations were assessed by logistic regression analysis. RESULTS: Seventy six percent (104/136) of the patients had at least one extrahepatic manifestation. Clinical manifestations included fatigue (59.6%), kidney impairment (25.0%), type 2 diabetes (22.8%), paresthesia (19.9%), arthralgia (18.4%), palpable purpura (17.6%), lymphadenopathy (16.2%), pulmonary fibrosis (15.4%), thyroid dysfunction (14.7%), Raynaud’s phenomenon (11.8%), B-cell lymphoma (8.8%), sicca syndrome (6.6%), and lichen planus (5.9%). The biological manifestations included cryoglobulin production (37.5%), thrombocytopenia (31.6%), and autoantibodies: anti-nuclear (18.4%), anti-smooth muscle (16.9%), anti-neutrophil cytoplasm (13.2%) and anti-cardiolipin (8.8%). All extrahepatic manifestations showed an association with cryoglobulin-positivity, with the exception of thyroid dysfunction, sicca syndrome, and lichen planus. Risks factors for the presence of extrahepatic manifestations (univariate analysis) were: age ≥ 60 years, female gender, virus transmission by blood transfusions, longstanding infection (≥ 20 years), and extensive liver fibrosis. The most significant risks factors (multivariate analysis) were longstanding infection and extensive liver fibrosis. CONCLUSION: We observed a high prevalence of extrahepatic manifestations in patients with chronic HCV infection. Most of these manifestations were associated with impaired lymphoproliferation and cryoglobulin

  14. Chronic hepatitis C virus infection: prevalence of extrahepatic manifestations and association with cryoglobulinemia in Bulgarian patients.

    PubMed

    Stefanova-Petrova, Diana V; Tzvetanska, Anelia H; Naumova, Elisaveta J; Mihailova, Anastasia P; Hadjiev, Evgenii A; Dikova, Rumiana P; Vukov, Mircho I; Tchernev, Konstantin G

    2007-12-28

    To assess the prevalence of extrahepatic manifestations in Bulgarian patients with chronic hepatitis C virus (HCV) infection and identify the clinical and biological manifestations associated with cryoglobulinemia. The medical records of 136 chronically infected HCV patients were reviewed to assess the prevalence of extrahepatic manifestations. Association between cryoglobulin-positivity and other manifestations were identified using chi2 and Fisher's exact test. Risk factors for the presence of extrahepatic manifestations were assessed by logistic regression analysis. Seventy six percent (104/136) of the patients had at least one extrahepatic manifestation. Clinical manifestations included fatigue (59.6%), kidney impairment (25.0%), type 2 diabetes (22.8%), paresthesia (19.9%), arthralgia (18.4%), palpable purpura (17.6%), lymphadenopathy (16.2%), pulmonary fibrosis (15.4%), thyroid dysfunction (14.7%), Raynaud's phenomenon (11.8%), B-cell lymphoma (8.8%), sicca syndrome (6.6%), and lichen planus (5.9%). The biological manifestations included cryoglobulin production (37.5%), thrombocytopenia (31.6%), and autoantibodies: anti-nuclear (18.4%), anti-smooth muscle (16.9%), anti-neutrophil cytoplasm (13.2%) and anti-cardiolipin (8.8%). All extrahepatic manifestations showed an association with cryoglobulin-positivity, with the exception of thyroid dysfunction, sicca syndrome, and lichen planus. Risks factors for the presence of extrahepatic manifestations (univariate analysis) were: age > or = 60 years, female gender, virus transmission by blood transfusions, longstanding infection (> or = 20 years), and extensive liver fibrosis. The most significant risks factors (multivariate analysis) were longstanding infection and extensive liver fibrosis. We observed a high prevalence of extrahepatic manifestations in patients with chronic HCV infection. Most of these manifestations were associated with impaired lymphoproliferation and cryoglobulin production. Longstanding

  15. Localization of hepatitis C virus in cutaneous vasculitic lesions in patients with type II cryoglobulinemia.

    PubMed

    Agnello, V; Abel, G

    1997-11-01

    To investigate the role of hepatitis C virus (HCV) in the pathogenesis of the cutaneous vasculitis in patients with type II cryoglobulinemia. Using in situ hybridization detection of HCV, we studied 6 test patients and various control subjects. Serum HCV was quantitated, cryoglobulins were analyzed by column chromatography at 37 degrees C, and low-density lipoprotein (LDL) receptors on keratinocytes were detected using LDL labeled with fluorescent dye. In the cutaneous vasculitic lesions from test patients, but not control subjects, the HCV virion was found in association with IgM and IgG. HCV alone was detected in some vessel walls, and in skin and ductal epithelium and vascular endothelium in inflamed, but not normal, skin. Cryoglobulins showed HCV, monomeric IgM, and monomeric IgG, with little or no immune complexes. The extent of the lesions correlated with levels of viremia. Up-regulation of LDL receptors on keratinocytes was detected in inflamed, but not normal, skin. HCV was present in the cutaneous vasculitic lesions, most likely in complexes with IgM and IgG formed in situ. These findings and the correlation of the severity of the rash with the level of viremia suggest that HCV plays a major role in the pathogenesis of cutaneous vasculitis in these patients and strengthens the rationale for antiviral drug therapy. The presence of HCV in keratinocytes and ductal epithelial and vascular endothelial cells may be the in vivo manifestation of endocytosis of HCV by the LDL receptors that has recently been demonstrated in vitro. The up-regulation of LDL receptors on keratinocytes in inflamed skin is consistent with this postulation.

  16. Interactions between virus-related factors and post-transplant ascites in patients with hepatitis C and no cirrhosis: role of cryoglobulinemia.

    PubMed

    Tripon, Simona; Francoz, Claire; Albuquerque, Anna; Paradis, Valérie; Boudjema, Hamza; Voitot, Hélène; Belghiti, Jacques; Valla, Dominique; Durand, François

    2015-02-01

    Refractory ascites may appear in liver transplant recipients with recurrence of hepatitis C virus infection, even in the absence of advanced fibrosis. The mechanisms are unclear. The aim was to determine whether post-transplant cryoglobulinemia could be a predisposing factor for ascites in this population. Retrospective data of 82 liver transplant recipients with HCV recurrence surviving more than 1 year were collected. Cryoglobulinemia was systematically tested after transplantation. All patients had 1-year protocol biopsy with assessment of sinusoidal distension, perisinusoidal fibrosis, and centrolobular necrosis. Additional biopsies were performed when needed. Fourteen of 82 patients (17%) developed refractory ascites. When ascites appeared, fibrosis was stage F0-F1 in 36% and F2-F3 in 57%. Factors independently associated with post-transplant ascites were pretransplant refractory ascites (P = 0.001), fibrosis ≥stage 2 at 1 year (P = 0.002), perisinusoidal fibrosis at 1 year (P = 0.02), and positive cryoglobulinemia (P = 0.02). Patients with ascites had a significantly worse prognosis compared to those without ascites. Refractory ascites may occur in liver transplant recipients with HCV recurrence in the absence of advanced fibrosis. The finding that both positive cryoglobulinemia and perisinusoidal fibrosis at 1 year were significantly associated with ascites suggests that liver microangiopathy is involved in the mechanisms of HCV-related ascites. © 2014 Steunstichting ESOT.

  17. Persistent Persister Misperceptions

    PubMed Central

    Kim, Jun-Seob; Wood, Thomas K.

    2016-01-01

    Persister cells survive antibiotic treatment due to their lack of metabolism, rather than through genetic change, as shown via four seminal experiments conducted by the discoverers of the phenotype (Hobby et al., 1942; Bigger, 1944). Unfortunately, over seven decades of persister cell research, the literature has been populated by misperceptions that do not withstand scrutiny. This opinion piece examines some of those misunderstandings in the literature with the hope that by shining some light on these inaccuracies, the field may be advanced and subsequent manuscripts may be reviewed more critically. PMID:28082974

  18. General practitioners’ prescribing behaviour as a determinant of poor persistence with inhaled corticosteroids in children with respiratory symptoms: mixed methods study

    PubMed Central

    Klok, Ted; Kaptein, Ad A; Duiverman, Eric; Oldenhof, Frank S; Brand, Paul L P

    2013-01-01

    Objectives To evaluate general practitioners’ (GPs’) prescribing behaviour as a determinant of persistence with and adherence to inhaled corticosteroids (ICS) in children. Design Prospective observational study of persistence with and adherence to ICS followed by a focus group study of the GPs prescribing this treatment. Setting 7 primary care practices in the area of Zwolle, the Netherlands. Participants 134 children aged 2–12 years had been prescribed ICS in the year before the study started by their 19 GPs. Main outcome measures Patterns and motives of GPs’ prescribing behaviour and the relationship with persistence with and adherence to ICS. Results GPs’ prescribing behaviour was characterised by prescribing short courses of ICS to children with various respiratory symptoms without follow-up for making a diagnosis of asthma. This was driven by the GPs’ pragmatic approach to deal with the large number of children with respiratory symptoms, and by beliefs about ICS which differed from currently available evidence. This prescribing behaviour was the main reason why 68 (51%) children did not persist with the use of ICS. In children with persistent use of ICS and a GP's advice to use ICS on a daily basis, the median (IQR) adherence was 70% (41–84%), and was similar for patients with persistent asthma and children lacking a diagnosis or symptoms of asthma. Conclusions Inappropriate prescription of ICS to children by GPs is common and drives the lack of persistence with ICS therapy in primary care. This finding should be taken into account when interpreting data from large prescription database studies. Improving primary healthcare providers’ knowledge and competence in diagnosing and managing asthma in children is needed. PMID:23558733

  19. Prevalence of anti-neutrophil cytoplasmic antibodies in patients with chronic hepatitis C infection associated mixed cryoglobulinemia.

    PubMed

    Cojocaru, M; Cojocaru, Inimioara Mihaela; Iacob, Simona Alexandra

    2006-01-01

    Chronic hepatitis C virus (HCV) has been linked to extrahepatic autoimmune phenomena. In addition, a variety of autoantibodies are found in patients with HCV. Anti-neutrophil cytoplasmic antibodies (ANCA) have been considered to be highly specific for systemic small vessel vasculitides with renal involvement. The prevalence, nature, a clinical significance of anti-neutrophil cytoplasmic antibodies (ANCA) in serum samples of patients with HCV were therefore investigated. A prospective study of 67 consecutive patients with chronic HCV with no evidence of previous hepatitis B virus (HBV) infection or any other autoimmune disorder. Twenty-seven patients with HBV and 35 healthy volunteers matched for age and sex served as control groups. Anti-neutrophil cytoplasmic antibodies in the serum samples were measured by indirect immunofluorescence assay. The group of patients with HCV and ANCA in their serum showed significantly higher total IgG levels, a higher incidence of antinuclear antibodies, and viraemia (HCV RNA) than the ANCA negative patients. None of the patients with HCV and ANCA showed any clinical manifestations related to those autoantibodies. This study clearly shows a high prevalence of ANCA in the serum of patients with HCV. The role of these autoantibodies on the course of HCV infection and their clinical significance has not been determined yet. In conclusion, ANCA are not only markers of small vessel vasculitides, but can also be (false?) positive in patients with HCV infection. A hepatitis C associated vasculitis should be considered in the differential diagnosis. Determination of target antigens for ANCA is indispensable. Interpretation and therapeutic decisions concerning ANCA associated HCV should only be performed within the clinical context.

  20. Usefulness of anti-CCP antibodies in patients with hepatitis C virus infection with or without arthritis, rheumatoid factor, or cryoglobulinemia.

    PubMed

    Liu, Feng-Cheng; Chao, You-Chen; Hou, Tsung-Yun; Chen, Hsiang-Cheng; Shyu, Rong-Yaun; Hsieh, Tsai-Yuan; Chen, Chen-Hung; Chang, Deh-Ming; Lai, Jenn-Haung

    2008-04-01

    The presence of antibodies to cyclic citrullinated peptide (CCP) has high specificity in the diagnosis of rheumatoid arthritis (RA). Hepatitis C virus (HCV) infection may induce extra-hepatic manifestations, such as polyarthritis that mimic RA. The aim of this study was to determine the prevalence of anti-CCP antibodies in HCV-infected patients with or without arthritis, rheumatoid factor (RF), or cryoglobulinemia and to investigate whether anti-CCP antibodies may be helpful in discriminating patients with RA from patients with HCV-associated arthropathy. A total of 44 patients with RA, 34 patients with HCV infections, and 42 control patients with non-RA rheumatic diseases were recruited for the study. Anti-CCP antibody levels were determined by enzyme-linked immunosorbent assay. We found that, consistent with other reports, patients with RA were more likely to have high titers of anti-CCP antibody than HCV-infected or control patients. A significant number of HCV-infected patients with neither RF nor cryoglobulinemia were also positive for anti-CCP antibodies (the three positive values were 36.10, 8.65, and 5.83 U/ml, P < 0.01 compared with the control patients). The presence of cryoglobulinemia and/or RF in HCV-infected patients did not affect the anti-CCP outcomes. Although anti-CCP antibodies remain to be a very useful tool in discriminating RA from non-RA, HCV-infected patients with neither RF nor cryoglobulinemia may have anti-CCP antibodies. Because of limited patient numbers, this tentative conclusion may need further confirmation with inclusion of more patient population.

  1. Portraits of Success: A Mixed-Method Study of the Enrollment, Persistence, and Success Experiences of Female Graduate Engineering Students at a Hispanic Serving Institution

    ERIC Educational Resources Information Center

    Aguirre-Covarrubias, Sandra

    2013-01-01

    The current study addresses the underrepresentation of female graduate engineering students. Specifically, its purpose was to gain insight on how enrollment, persistence, and success factors are experienced by female graduate engineering students at a Hispanic Serving Institution located on the U.S.-Mexico border. The topic of underrepresentation…

  2. Prevalence of cryoglobulinemia and serological markers of autoimmunity in human immunodeficiency virus infected individuals: a cross-sectional study of 97 patients.

    PubMed

    Bonnet, Fabrice; Pineau, Jean-Jacques; Taupin, Jean-Luc; Feyler, Anne; Bonarek, Mojgan; de Witte, Sten; Bernard, Noelle; Lacoste, Denis; Morlat, Philippe; Beylot, Jacques

    2003-09-01

    Autommune diseases could constitute one emerging cause of morbidity in patients infected with human immunodeficiency virus (HIV) due to the chronicity of the infection and to the high level of B cell stimulation induced by HIV. We conducted a cross-sectional study investigating the clinical and biological signs of autoimmunity in HIV infected patients. We studied the following plasma immunological variables: antinuclear antibodies (ANA) and antibodies to extractable nuclear antigens, antiphospholipids, anticardiolipins (aCL), antineutrophil cytoplasmic antibodies (ANCA), rheumatoid factor (RF), cryoglobulinemia, total complement, and C4 factor. HIV-RNA, CD4+ cell count, and serological status for hepatitis B (HBV) and C virus (HCV) were also studied. Clinical signs of autoimmune diseases were noted. In total, 97 patients were investigated (men 74%). Median age was 38 years (range 20-64). Median CD4+ count and HIV-RNA were 333/mm3 and 1662 copies/ml, respectively. Coinfection by HBV and HCV was present in 7% and 64% of the patients. In patients with HIV only, we detected cryoglobulinemia in 17% of patients, a positive RF in 19%, ANA > 1/100 in 21%, aCL in 51%, and ANCA > 1/20 in 17% (most of them type C by ELISA). There was a trend for a higher level of cryoglobulinemia and aCL in patients having CD4 lymphocyte counts > 350/mm3 than in others (25% vs 11%, p = 0.26, and 63% vs 42%, p = 0.23, respectively). Patients coinfected with HCV had a higher prevalence of cryoglobulinemia than HCV-free patients (42% vs 17%; p = 0.01). Prevalence of other immunological abnormalities was not different between patients with HIV only and HCV coinfected patients. Thirty patients expressed at least one clinical sign compatible with autoimmune disease. Patients with cryoglobulinemia more often had coinfection with HCV (OR 6.64, 95% CI 1.87-23.57) and IgM > 1.9 g/l (OR 6.16, 95% CI 2.15-17.67). Humoral immunological abnormalities are frequent in patients with HIV, but are rarely

  3. Mixed T Cell Chimerism After Allogeneic Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia Using an Alemtuzumab-Containing Regimen Is Shaped by Persistence of Recipient CD8 T Cells.

    PubMed

    Grimaldi, Francesco; Potter, Victoria; Perez-Abellan, Pilar; Veluchamy, John P; Atif, Muhammad; Grain, Rosemary; Sen, Monica; Best, Steven; Lea, Nicholas; Rice, Carmel; Pagliuca, Antonio; Mufti, Ghulam J; Marsh, Judith C W; Barber, Linda D

    2017-02-01

    Prevention of graft-versus-host disease (GVHD) is paramount for allogeneic hematopoietic stem cell transplantation (HSCT) to treat nonmalignant diseases. We previously reported that allogeneic HSCT for severe aplastic anemia (SAA) using the fludarabine, cyclophosphamide, and alemtuzumab (Campath-1H) (FCC) regimen is associated with a very low risk of GVHD and excellent clinical outcomes. We now report a single-center study of 45 patients with longer follow-up and investigation of lymphocyte recovery. Overall survival (OS) was 93%, and event-free survival (EFS) was 90.7%. Acute and chronic GVHD each occurred in 6 patients (13.3%), and only 1 case was severe. Mixed T cell chimerism was frequent and persisted after cessation of immunosuppression. T cells were extensively depleted, representing only 11.3% of lymphocytes at day 30 and rising to 43.8% by 1 year, but still significantly below normal levels (67.2%; P = .018), and deficiency persisted after immunosuppressive therapy (IST) withdrawal. Depletion of CD4 T cells was particularly profound, causing inversion of the normal CD4:CD8 T cell ratio. T cell subset composition was also abnormal, with memory and effector T cells predominating for at least 6 months after FCC HSCT. Analysis of T cell subset chimerism showed that CD4 T cells were predominantly donor-derived at 1 year, whereas recipient-derived CD8 T cells shaped mixed chimerism with a notable contribution of recipient effector CD8 T cells. The prolonged mixed T cell chimerism after IST withdrawal and low incidence of GVHD indicates the establishment of mutual tolerance, but the low incidence of viral disease suggests maintenance of antiviral immunity. Our study shows that despite the abnormal T cell profile after allogeneic HSCT for SAA using the FCC regimen, this regimen is conducive to an excellent clinical outcome.

  4. Persistence in ozone scaling under the Hurst exponent as an indicator of the relative rates of chemistry and fluid mechanical mixing in the stratosphere

    SciTech Connect

    Tuck, A.F.; Hovde, S.J.; Proffitt, M.H.

    1999-12-09

    The observed self-affine fractal behavior of ozone, wind, and temperature in the stratosphere is used to produce an indication of the rate of occurrence of chemistry relative to that of fluid mixing which, unlike the usual method, is independent of an assumed mechanism sequence of elementary chemical steps followed by application of the law of mass action to obtain differential equations describing the temporal and spatial evolution of the reacting gases. Rather, the occurrence of chemistry is deduced from the scaling of the observed variability; it is applied empirically to deduce the presence of chemical processes that are faster than fluid mechanical mixing above an altitude of 19 km during a balloon flight, and in the Antarctic spring, Arctic summer, and Arctic winter during high altitude aircraft flights. The method should apply to any volume of reacting molecules to which the equations of fluid motion apply and for which measurements can be made over a range of scales.

  5. Alpha-chemokine CXCL10 and beta-chemokine CCL2 serum levels in patients with hepatitis C-associated cryoglobulinemia in the presence or absence of autoimmune thyroiditis.

    PubMed

    Antonelli, Alessandro; Ferri, Clodoveo; Fallahi, Poupak; Ferrari, Silvia Martina; Frascerra, Silvia; Carpi, Angelo; Nicolini, Andrea; Ferrannini, Ele

    2008-09-01

    Chemokines have been identified to play an important role in endocrine autoimmune disease and hepatitis C chronic infection. To our knowledge, no study has evaluated serum levels of CXCL10 and CCL2 in patients with "mixed cryoglobulinemia and hepatitis C virus chronic infection" (MC) in the presence or absence of autoimmune thyroiditis (AT). Serum CXCL10 and CCL2 were assayed in 60 patients with MC, in 45 patients with "MC with AT" (MC + AT), and in controls (60 without [control 1] and 45 with AT [control 2]). CXCL10 was significantly higher (1) in control 2 than in control 1 (P < .001), (2) in MC than in control 1, and (3) in MC + AT than in controls 1 and 2 and in MC (P = .002). A high CXCL10 level (>mean + SD control 1; >167 pg/mL) was present in 7% control 1, 21% control 2, 49% MC, and 78% MC + AT (P < .0001). CCL2 was significantly higher in MC and in MC + AT than in control 1 or in control 2 (P < .01). A high CCL2 level (>mean + SD control 1; >730 pg/mL) was present in 2% control 1, 1% control 2, 18% MC, and 21% MC + AT (P < .0001). The study demonstrates high CXCL10 and CCL2 serum levels in patients with MC; CXCL10 in MC + AT is significantly higher than that in MC. Future studies in larger series will be needed to evaluate the potential usefulness of serum CXCL10 and CCL2 determination as a prognostic marker in the follow-up of MC patients, also in relation to the presence of AT.

  6. [Persistent diarrhea

    PubMed

    Andrade, J A; Moreira, C; Fagundes Neto, U

    2000-07-01

    INTRODUCTION: Persistent diarrhea has high impact on infantile morbidity and mortality rates in developing countries. Several studies have shown that 3 to 20% of acute diarrheal episodes in children under 5 years of age become persistent. DEFINITION: Persistent diarrhea is defined as an episode that lasts more than 14 days. ETIOLOGY: The most important agents isolated in persistent diarrhea are: Enteropathogenic E. coli (EPEC), Salmonella, Enteroaggregative E. coli (EAEC), Klebisiella and Cryptosporidium. CLINICAL ASPECTS: In general, the clinical characteristics of patients with persistent diarrhea do not change with the pathogenic agent. Persistent diarrhea seems to represent the final result of a several insults a infant suffers that predisposes to a more severe episode of diarrhea due to a combination of host factors and high rates of enviromental contamination. Therefore, efforts should be made to promptly treat all episodes of diarrhea with apropriate follow-up. THERAPY: The aim of the treatment is to restore hydroelectrolytic deficits and to replace losses until the diarrheal ceases. It is possible in the majority of the cases, using oral rehydration therapy and erly an appropriate type of diet. PREVENTION: It is imperative that management strategies also focus on preventive aspects. The most effective diarrheal prevention strategy in young infants worldwide is promotion of exclusive breast feeding.

  7. Patient outcomes and experiences of an acupuncture and self-care service for persistent low back pain in the NHS: a mixed methods approach

    PubMed Central

    2013-01-01

    Background Supported self-management, acupuncture and information can help reduce the symptoms of low back pain. These approaches are currently recommended by NICE guidance as treatment options for patients with persistent low back pain. However, there has been no previous evaluation of a service providing them together for this common problem. The purpose of this service evaluation was to report patient outcomes and experiences of the Beating Back Pain Service (BBPS), a pilot service based in a primary and community care setting, delivering acupuncture, self-management and information to patients with chronic low back pain. Methods Patients completed a questionnaire at three time points: pre-BBPS, immediately post-BBPS and three months post-BBPS. Outcome measures included the Bournemouth Questionnaire (measuring musculoskeletal, MSK, problems), EuroQoL-5D (measuring quality of life), Pain and Self-efficacy Questionnaire, and additional questions on medication use, physical activity, understanding of pain and positive well-being. Additionally, the STarT Back (measuring risk of developing chronic pain) was collected at BBPS information sessions. Non-parametric tests were used to evaluate pre- and post- variables. Questionnaires also collected qualitative data (open-text responses) regarding patient views and experiences of the BBPS, which were analysed using thematic analysis. Results 80 (out of 108) patients who attended the initial BBPS information session agreed to participate in the service evaluation (mean age 47 years, 65% female). 65 patients attended subsequent BBPS acupuncture and/or self-management sessions and were asked to complete post-treatment questionnaires; complete datasets were available for 61 patients. There were statistically significant improvements over time for pain (p <0.0001), quality of life (p = 0.006), understanding of pain (p <0.001), physical activity (p = 0.047) and relaxation (p = 0.012). Post-hoc analysis revealed that

  8. Semibiotic Persistence

    NASA Astrophysics Data System (ADS)

    Prothmann, C.; Zauner, K.-P.

    From observation, we find four different strategies to successfully enable structures to persist over extended periods of time. If functionally relevant features are very large compared to the changes that can be effectuated by entropy, the functional structure itself has a high enough probability to erode only slowly over time. If the functionally relevant features are protected from environmental influence by sacrificial layers that absorb the impinging of the environment, deterioration can be avoided or slowed. Loss of functionality can be delayed, even for complex systems, by keeping alternate options for all required components available. Biological systems also apply information processing to actively counter the impact of entropy by mechanisms such as self-repair. The latter strategy increases the overall persistence of living systems and enables them to maintain a highly complex functional organisation during their lifetime and over generations. In contrast to the other strategies, information processing has only low material overhead. While at present engineered technology is far from achieving the self-repair of evolved systems, the semibiotic combination of biological components with conventionally engineered systems may open a path to long-term persistence of functional devices in harsh environments. We review nature's strategies for persistence, and consider early steps taken in the laboratory to import such capabilities into engineered architectures.

  9. Cryoglobulinemia in Sjögren Syndrome: A Disease Subset that Links Higher Systemic Disease Activity, Autoimmunity, and Local B Cell Proliferation in Mucosa-associated Lymphoid Tissue.

    PubMed

    Quartuccio, Luca; Baldini, Chiara; Priori, Roberta; Bartoloni, Elena; Carubbi, Francesco; Alunno, Alessia; Gandolfo, Saviana; Colafrancesco, Serena; Giacomelli, Roberto; Gerli, Roberto; Valesini, Guido; Bombardieri, Stefano; De Vita, Salvatore

    2017-08-01

    To compare systemic disease activity by validated tools, i.e., the European League Against Rheumatism Sjögren Syndrome Disease Activity Index (ESSDAI) and the Clinical ESSDAI (ClinESSDAI) scores, between primary Sjögren syndrome (pSS) with positive serum cryoglobulins and pSS without serum cryoglobulins. There were 825 consecutive patients with pSS who were retrospectively evaluated. The ESSDAI and the ClinESSDAI scores were significantly higher in cryoglobulin-positive patients (p < 0.0001, for both scores). Cryoglobulinemia was significantly associated with these domains: constitutional (p = 0.003), lymphadenopathy (p = 0.007), glandular (p = 0.0002), cutaneous (p < 0.0001), peripheral nervous system (p < 0.0001), hematological (p = 0.004), and biological (p < 0.0001). Cryoglobulin-positive patients show the highest systemic activity in pSS.

  10. Non HCV-related infectious cryoglobulinemia vasculitis: Results from the French nationwide CryoVas survey and systematic review of the literature.

    PubMed

    Terrier, Benjamin; Marie, Isabelle; Lacraz, Adeline; Belenotti, Pauline; Bonnet, Fabrice; Chiche, Laurent; Graffin, Bruno; Hot, Arnaud; Kahn, Jean-Emmanuel; Michel, Catherine; Quemeneur, Thomas; de Saint-Martin, Luc; Hermine, Olivier; Léger, Jean-Marc; Mariette, Xavier; Senet, Patricia; Plaisier, Emmanuelle; Cacoub, Patrice

    2015-12-01

    In patients with infectious cryoglobulinemia vasculitis (CryoVas) in the absence of hepatitis C virus infection, data on presentation, therapeutic management and outcome are lacking. We conducted a nationwide survey that included patients with HCV-negative CryoVas. We describe here the presentation, therapeutic management and outcome of 18 patients with non-HCV infectious CryoVas and 27 additional patients identified form a systematic review of the literature. We included 18 patients, mean age 57.9±13.5 years. Infectious causes were viral infections in 8 patients [hepatitis B virus (HBV) in 4, and cytomegalovirus, Epstein Barr virus, parvovirus B19 and human immunodeficiency virus in one case each], pyogenic bacterial infection in 6 patients, parasitic infection in 2 patients, and leprosy and candidiasis in one case each. Baseline manifestations were purpura (78%), glomerulonephritis (28%), arthralgia (28%), peripheral neuropathy (22%), skin necrosis (22%), cutaneous ulcers (17%), and myalgia (11%). Cryoglobulinemia was type II in 2/3 of cases. Most cases received specific anti-infectious therapy as first-line therapy, sometimes associated with corticosteroids, achieving sustained remission in the majority of cases. Refractory or relapsing patients, frequently related to HBV infection, showed a complete remission after rituximab in addition to antiviral therapy. In contrast, corticosteroids and/or immunosuppressive agents used in the absence of anti-infectious agents were frequently associated with refractory CryoVas. Viral and pyogenic bacterial infections represent the main causes of non-HCV infectious CryoVas. Antimicrobial therapy is commonly associated with sustained remission. Immunosuppressive agents should be considered only as a second-line option in patients with refractory vasculitis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Biological markers of liver fibrosis and activity as non-invasive alternatives to liver biopsy in patients with chronic hepatitis C and associated mixed cryoglobulinemia vasculitis.

    PubMed

    Sène, Damien; Limal, Nicholas; Messous, Djamila; Ghillani-Dalbin, Pascale; Charlotte, Frédéric; Thiollière, Jean-Marie; Piette, Jean-Charles; Imbert-Bismut, Françoise; Halfon, Philippe; Poynard, Thierry; Cacoub, Patrice

    2006-07-01

    We assessed the reliability of non-invasive biological scoring indexes (Fibrotest-Actitest [FT-AT], Forns, APRI, age-platelet, platelet, hyaluronic acid) as non-invasive alternatives to liver biopsy (LB) in 138 HCV-infected patients. Thirty-six of 138 (26%) patients had systemic vasculitis, 27% significant serum inflammation, 47% fibrosis (F2F3F4) on LB. The diagnostic value of FT (F2F3F4 vs. F0F1) was assessed by an AUC of 0.83, without difference regarding to systemic vasculitis or serum inflammation. A discordance between FT-AT and the Metavir scoring indexes, present in 29% of patients, was associated with serum hemolysis and male but not with systemic vasculitis or serum inflammation. The other non-invasive biological tests were not influenced by serum inflammation or systemic vasculitis but were less reliable than FT (P

  12. IgG3 subclass: A possible trigger of mixed cryoglobulin cascade in hepatitis C virus chronic infection.

    PubMed

    Basile, Umberto; Gulli, Francesca; Gragnani, Laura; Fognani, Elisa; Napodano, Cecilia; Pocino, Krizia; Zignego, Anna Linda; Rapaccini, Gian Ludovico

    2017-06-24

    HCV is a hepatotropic and lymphotropic virus and is the most frequent cause of "benign" mono-oligoclonal B-lymphocyte proliferation, observed in mixed cryoglobulinemia (MC). The study aims to investigate the presence, prevalence and characteristics of the subclasses of cryoglobulins in HCV-patients to look for a relationship with MC. Fifty HCV-infected patients with cryoglobulins were enrolled. IgG subclasses were characterized in cryoprecipitate, and serum IgG and IgM Rheumatoid Factor (RF) were determined. Patients were stratified into two subgroups according to the presence of IgG3 subclass. Differences were observed in supernatant IgM, IgG3-positive and IgG3-negative patients with a higher IgM concentration in the IgG3-negative cohort (p=0.03). Higher IgM-RF was detected in the IgG3-negative group (p=0.01). IgG3-positive group showed higher IgG-RF compared to the IgG3-negative group (p<0.0001). IgG3-negative/monoclonal-IgM patients had higher cryocrit compared to IgG3-negative/polyclonal-IgM patients (p<0.01). C4 levels were higher in the polyclonal-IgM group compared to monoclonal-IgM group (p<0.01). We speculate that cryoglobulins are part of a progressive clonal selection process in which, B-cells are stimulated to produce oligoclonal IgG3 with RF activity. The persistence of the antigenic stimulus elicits the production of polyclonal IgM-RF and subsequently the formation of oligoclonal IgG/polyclonal IgM containing cryoglobulins. In the last stage, a monoclonal IgM-RF clone is formed which may coexist with a monoclonal IgG3-RF clone. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  13. Increased frequency of antibodies to ubiquitous viruses in essential mixed cryoglobulinaemia.

    PubMed Central

    Fiorini, G; Bernasconi, P; Sinico, R A; Chianese, R; Pozzi, F; D'Amico, G

    1986-01-01

    Antibodies to ubiquitous Herpes viruses have been studied in 13 patients with type II essential mixed cryoglobulinemia (EMC), and in two different control groups. All the EMC patients had monoclonal IgM kappa in their cryoprecipitates. IgM antibodies to the viral capsid antigen (VCA) of Epstein-Barr virus (EBV) were found in the sera of 11 EMC patients but all the cryoprecipitates were negative. IgG antibodies were also present in the sera of all and in the cryoprecipitates of some patients. In contrast, the number of subjects with antibodies to Cytomegalovirus (CMV) and Hepatitis B Virus (HBV) was not higher than in controls. Possible correlations between EMC and EBV infection are discussed. PMID:3015457

  14. Persistent depressive disorder

    MedlinePlus

    Persistent depressive disorder (PDD) is a chronic (ongoing) type of depression in which a person's moods are regularly low. ... are not as severe as with major depression . Persistent depressive disorder used to be called dysthymia.

  15. Persistent heap Management library

    SciTech Connect

    2012-01-17

    PERM is a C library for persistent heap management and is intended for use with a dynamic-memory allocator (e.g. malloc, free). The PERM memory allocator replaces the standard C dynamic memory allocation functions with compatible versions that provide persistent memory to application programs. Memory allocated with the PERM allocatory will persist between program invocations after a call to a checkpoint function. This function essentially saves the state of the heap and registered global variables to a file which may reside in flash memory or other node local storage. A few other functions are also provided by the library to manage checkpoint files. Global variables in an application can be marked persistent and be included in a checkpoint by using a compiler attribute defined as PERM. The PERM checkpoint methof is not dependent on the programming model ans works with distributed memory or shared memory programs.

  16. Unusually persistent complainants.

    PubMed

    Lester, Grant; Wilson, Beth; Griffin, Lynn; Mullen, Paul E

    2004-04-01

    Querulous paranoia may have disappeared from the psychiatric literature, but is it flourishing in modern complaints organisations and the courts? To investigate the unusually persistent complainants who lay waste to their own lives and place inordinate demands and stress on complaints organisations. Complaints officers completed questionnaires on both unusually persistent complainants and matched controls. Persistent complainants (distinguished by their pursuit of vindication and retribution) consumed time and resources and resorted to both direct and veiled threats. Attempts to distinguish these people from a control group on the basis of the manner in which their claims were initially managed failed. Persistent complainants' pursuit of vindication and retribution fits badly with complaints systems established to deliver reparation and compensation. These complainants damaged the financial and social fabric of their own lives and frightened those dealing with their claims. The study suggests methods of early detection and alternative management strategies.

  17. Glyphosate persistence in seawater.

    PubMed

    Mercurio, Philip; Flores, Florita; Mueller, Jochen F; Carter, Steve; Negri, Andrew P

    2014-08-30

    Glyphosate is one of the most widely applied herbicides globally but its persistence in seawater has not been reported. Here we quantify the biodegradation of glyphosate using standard "simulation" flask tests with native bacterial populations and coastal seawater from the Great Barrier Reef. The half-life for glyphosate at 25 °C in low-light was 47 days, extending to 267 days in the dark at 25 °C and 315 days in the dark at 31 °C, which is the longest persistence reported for this herbicide. AMPA, the microbial transformation product of glyphosate, was detected under all conditions, confirming that degradation was mediated by the native microbial community. This study demonstrates glyphosate is moderately persistent in the marine water under low light conditions and is highly persistent in the dark. Little degradation would be expected during flood plumes in the tropics, which could potentially deliver dissolved and sediment-bound glyphosate far from shore.

  18. Persistent currents in mesoscopic Fibonacci rings

    SciTech Connect

    Jin, G.J.; Wang, Z.D.; Hu, A.; Jiang, S.S.

    1997-04-01

    In the framework of a tight-binding model, we study energy spectra and persistent currents in mesoscopic Fibonacci rings threaded by a magnetic flux. It is found that the flux-dependent electron eigenenergies E({Phi}) in mesoscopic Fibonacci rings still form ``bands`` with respect to the flux {Phi}, but there is a scaling relation between the total ``bandwidth`` and the Fibonacci number. When the strength of the one-dimensional quasiperiodic potential increases, the persistent current decreases rapidly. Interestingly, for a generalized mixing model of mesoscopic Fibonacci rings, free-electron-like persistent current may appear if the number of electrons of the system takes a specific value. {copyright} {ital 1997} {ital The American Physical Society}

  19. The Sunk Cost Effect with Pigeons: Some Determinants of Decisions about Persistence

    ERIC Educational Resources Information Center

    Macaskill, Anne C.; Hackenberg, Timothy D.

    2012-01-01

    The sunk cost effect occurs when an individual persists following an initial investment, even when persisting is costly in the long run. The current study used a laboratory model of the sunk cost effect. Two response alternatives were available: Pigeons could persist by responding on a schedule key with mixed ratio requirements, or escape by…

  20. The Sunk Cost Effect with Pigeons: Some Determinants of Decisions about Persistence

    ERIC Educational Resources Information Center

    Macaskill, Anne C.; Hackenberg, Timothy D.

    2012-01-01

    The sunk cost effect occurs when an individual persists following an initial investment, even when persisting is costly in the long run. The current study used a laboratory model of the sunk cost effect. Two response alternatives were available: Pigeons could persist by responding on a schedule key with mixed ratio requirements, or escape by…

  1. Persistent luminescence nanothermometers

    NASA Astrophysics Data System (ADS)

    Martín Rodríguez, Emma; López-Peña, Gabriel; Montes, Eduardo; Lifante, Ginés; García Solé, José; Jaque, Daniel; Diaz-Torres, Luis Armando; Salas, Pedro

    2017-08-01

    Persistent phosphorescence nanoparticles emitting in the red and near-infrared spectral regions are strongly demanded as contrast nanoprobes for autofluorescence free bioimaging and biosensing. In this work, we have developed Sr4Al14O25:Eu2+, Cr3+, Nd3+ nanopowders that produce persistent red phosphorescence peaking at 694 nm generated by Cr3+ ions. This emission displays temperature sensitivity in the physiological temperature range (20-60 °C), which makes these nanoparticles potentially useful as fluorescence (contactless) nanothermometers operating without requiring optical excitation. Nd3+ ions, which act as shallow electron traps for the red Cr3+ persistent emission, also display infrared emission bands, extending the fluorescence imaging capability to the second biological window. This unique combination of properties makes these nanoparticles multifunctional luminescent probes with great potential applications in nanomedicine.

  2. Visual persistence and cinema?

    PubMed

    Galifret, Yves

    2006-01-01

    In Faraday and Plateau's days, both apparent motion and the fusion of intermittent lights, two phenomena that are hardly connected, were explained by retinal persistence. The works of Exner and of the 'Gestalt' psychologists, as well as the modern works on 'sampled' motion and smooth motion, disregarded retinal persistence. One tried, originally, to measure this persistence using intermittent stimulation, but under the pressure of practical concern, what was established in 1902 was the logarithmic relation between fusion frequency and the intensity of the stimulation. One had to wait until the 1950s for the use of harmonic analysis to finally allow a renewal in which many problems that, for decades, had only given rise to discussions that led nowhere and to groundless assertions, were correctly stated and easily solved.

  3. Metabolic Perspectives on Persistence

    PubMed Central

    Hartman, Travis E.; Wang, Zhe; Jansen, Robert S.; Gardete, Susana; Rhee, Kyu Y.

    2016-01-01

    SUMMARY Accumulating evidence has left little doubt about the importance of persistence or metabolism in the biology and chemotherapy of tuberculosis. However, knowledge of the intersection between these two factors has begun to emerge only recently. Here, we provide a focused review of metabolic characteristics associated with M. tuberculosis persistence. We focus on metabolism because it is the biochemical foundation of all physiologic processes and a distinguishing hallmark of M. tuberculosis’s physiology and pathogenicity. In addition, it serves as the chemical interface between host and pathogen. However, existing knowledge derives largely from physiologic contexts in which replication is the primary biochemical objective. The goal of this review is to reframe existing knowledge of M. tuberculosis metabolism in the context of persistence where quiescence is often a key distinguishing characteristic. Such a perspective may help guide ongoing efforts to develop more efficient cures and inform on novel strategies to break the cycle of transmission sustaining the pandemic. PMID:28155811

  4. Persistence and financial markets

    NASA Astrophysics Data System (ADS)

    Jain, S.

    2007-09-01

    The persistence phenomenon is studied in a financial context by using a novel mapping of the time evolution of the values of shares in a portfolio onto Ising spins. The method is applied to historical data from the London Financial Times Stock Exchange 100 index (FTSE 100) over an arbitrarily chosen period. By following the time dependence of the spins, we find evidence for a power law decay of the proportion of shares that remain either above or below their ‘starting’ values. As a result, we estimate a persistence exponent for the underlying financial market to be ≈0.5. Preliminary results from computer simulations on persistence in the economic dynamics of a toy model appear to reproduce the behaviour observed in real markets.

  5. Persistence in financial markets

    NASA Astrophysics Data System (ADS)

    Jain, S.; Buckley, P.

    2006-03-01

    Persistence is studied in a financial context by mapping the time evolution of the values of the shares quoted on the London Financial Times Stock Exchange 100 index (FTSE 100) onto Ising spins. By following the time dependence of the spins, we find evidence for power law decay of the proportion of shares that remain either above or below their 'starting' values. As a result, we estimate a persistence exponent for the underlying financial market to be θf˜0.5.

  6. Retention and Persistence Data.

    ERIC Educational Resources Information Center

    Sanford, Timothy R.

    Two studies are combined with an introductory section: one is "Persistence to Graduation for Freshmen Entering the University of North Carolina at Chapel Hill, 1967-75," by Timothy Sanford, and the second is "Freshman, Transfer, Professional, Masters, and Doctoral Student Retention at the University of North Carolina at Chapel…

  7. A Very Persistent Mistake

    ERIC Educational Resources Information Center

    McClelland, J. A. G.

    2011-01-01

    Articulated bodies with an internal energy source require to be coupled to an external mass in order to accelerate themselves but the typical text book assertion that the net force is provided by the external mass is not correct. Arguments are presented demonstrating that the assertion is incorrect and reasons are suggested for the persistence of…

  8. A Very Persistent Mistake

    ERIC Educational Resources Information Center

    McClelland, J. A. G.

    2011-01-01

    Articulated bodies with an internal energy source require to be coupled to an external mass in order to accelerate themselves but the typical text book assertion that the net force is provided by the external mass is not correct. Arguments are presented demonstrating that the assertion is incorrect and reasons are suggested for the persistence of…

  9. The Persistence of PCBs.

    ERIC Educational Resources Information Center

    Boyle, Robert H.; Highland, Joseph H.

    1979-01-01

    PCB's are one of the most persistent chemicals ever introduced into the environment by man. From very early in their history of manufacture PCB's were suspected of being hazardous to health, but public awareness of the hazard was slow in coming. (RE)

  10. Persistence to Graduate Education.

    ERIC Educational Resources Information Center

    Ethington, Corinna A.; Smart, John C.

    1986-01-01

    A study is reported of the relationship of family education and income, high school grades, academic and social self-confidence, undergraduate institutional selectivity and size, academic and social integration, overall college satisfaction, bachelor's degree attainment, and financial aid on students' persistence to graduate school. (MSE)

  11. Mixed Dementia

    MedlinePlus

    ... community Use our Virtual Library Treatment and outcomes back to top Because most people with mixed dementia are diagnosed with a single type of dementia, physicians often base their prescribing decisions on the type of dementia ...

  12. Persistent cultural systems.

    PubMed

    Spicer, E H

    1971-11-19

    I have indicated here some features of a kind of entity which I have called a cultural identity system, and I have focused on a variety of this general type-the persistent system. In general terms it is best described as a system of beliefs and sentiments concerning historical events. I suggest using the term "a people" for the human beings who, at any given time, hold beliefs of this kind. These are phenomena with which we have been long familiar, but they have not been systematically studied by any but a few investigators. I have emphasized that a persistent system is a cumulative cultural phenomenon, an open-ended system that defines a course of action for the people believing in it. Such peoples are able to maintain continuity in their experience and their conception of themselves in a wide variety of sociocultural environments. I hold that certain kinds of identifiable conditions give rise to this type of cultural system. These may best be summarized as an oppositional process involving the interactions of individuals in the environment of a state or a similar large-scale organization. The oppositional process frequently produces intense collective consciousness and a high degree of internal solidarity. This is accompanied by a motivation for individuals to continue the kind of experience that is "stored" in the identity system in symbolic form. The persistent identity system is more stable as a cultural structure than are large-scale political organizations. When large-scale states disintegrate, they often appear to decompose into cultural systems of the persistent type. Large-scale organizations also give rise to the kind of environment that can result in the formation of new persistent systems. It is possible that, while being formed, states depend for their impetus on the accumulated energy of persistent peoples. A proposition for consideration is that states tend to dissipate the energy of peoples after transforming that energy into state

  13. Optimization and Persistence

    DTIC Science & Technology

    1997-09-01

    and production costs are amplified by first-time applica- tion of high technology , security, and lim- ited production quantities. Alternate can...stred spendmg levels, average fleet age, average " technological advantage" of the fleet, and so forth. (The persistent features we discuss have all...a precise concept when dealing with nonmonetary units, such as technological advantage, but all elastic penalties are usually adjusted by the same

  14. Persistent interface fluid syndrome.

    PubMed

    Hoffman, Richard S; Fine, I Howard; Packer, Mark

    2008-08-01

    We present an unusual case of persistent interface fluid that would not resolve despite normal intraocular pressure and corneal endothelial replacement with Descemet-stripping endothelial keratoplasty. Dissection, elevation, and repositioning of the laser in situ keratomileusis flap were required to resolve the interface fluid. Circumferential corneal graft-host margin scar formation acting as a mechanical strut may have been the cause of the intractable interface fluid.

  15. Persistent Security, Then Development

    DTIC Science & Technology

    2010-08-01

    already been purchased, quite literally, with blood, sweat , and tears. Persistent security is the sufficient condition for stability operations and, in...outposts. 72 July-August 2010  MILITARY REVIEW to the coalition or drinking three cups of tea with a fence-sitting tribal leader turned his tribe to...largest bases demonstrate that there are still ideologically driven men who are willing to fight to the death. Building retaining walls and drinking cups

  16. Persistent benign pleural effusion.

    PubMed

    Porcel, J M

    In this narrative review we describe the main aetiologies, clinical characteristics and treatment for patients with benign pleural effusion that characteristically persists over time: chylothorax and cholesterol effusions, nonexpansible lung, rheumatoid pleural effusion, tuberculous empyema, benign asbestos pleural effusion and yellow nail syndrome. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  17. Persistent occiput posterior.

    PubMed

    Barth, William H

    2015-03-01

    Persistent occiput posterior (OP) is associated with increased rates of maternal and newborn morbidity. Its diagnosis by physical examination is challenging but is improved with bedside ultrasonography. Occiput posterior discovered in the active phase or early second stage of labor usually resolves spontaneously. When it does not, prophylactic manual rotation may decrease persistent OP and its associated complications. When delivery is indicated for arrest of descent in the setting of persistent OP, a pragmatic approach is suggested. Suspected fetal macrosomia, a biparietal diameter above the pelvic inlet or a maternal pelvis with android features should prompt cesarean delivery. Nonrotational operative vaginal delivery is appropriate when the maternal pelvis has a narrow anterior segment but ample room posteriorly, like with anthropoid features. When all other conditions are met and the fetal head arrests in an OP position in a patient with gynecoid pelvic features and ample room anteriorly, options include cesarean delivery, nonrotational operative vaginal delivery, and rotational procedures, either manual or with the use of rotational forceps. Recent literature suggests that maternal and fetal outcomes with rotational forceps are better than those reported in older series. Although not without significant challenges, a role remains for teaching and practicing selected rotational forceps operations in contemporary obstetrics.

  18. Ion mixing

    NASA Technical Reports Server (NTRS)

    Matteson, S.; Nicolet, M.-A.

    1983-01-01

    Recent experimental studies of the ion-mixing phenomenon are summarized. Ion mixing is differentiated from ion implantation and shown to be a useful technique for overcoming the sputter-dependent limitations of implantation processes. The fundamental physical principles of ion/solid interactions are explored. The basic experimental configurations currently in use are characterized: bilayered samples, multilayered samples, and samples with a thin marker layer. A table listing the binary systems (metal-semiconductor or metal-metal) which have been investigated using each configuration is presented. Results are discussed, and some sample data are plotted. The prospects for future application of ion mixing to the alteration of solid surface properties are considered. Practical applications are seen as restricted by economic considerations to the production of small, expensive components or to fields (such as the semiconductor industry) which already have facilities for ion implantation.

  19. Special Education Teacher Persistence

    ERIC Educational Resources Information Center

    Thorp, Sally A.

    2013-01-01

    The focus of this study was special education teachers, who remained in the teaching field 5 or more years. Through the use of qualitative mixed-methods study, variables contributing to their longevity were explored. Research indicates that 50% of special education teachers leave the field within five years of employment (Alliance for Education,…

  20. Learning's "Weak" Link to Persistence

    ERIC Educational Resources Information Center

    Wolniak, Gregory C.; Mayhew, Matthew J.; Engberg, Mark E.

    2012-01-01

    This study advances the understanding of college persistence by examining five dimensions of student learning in relation to second-year persistence. Two of the five dimensions of learning were found to be significant predictors of persistence, and each was moderated by social integration. (Contains 5 tables and 1 figure.)

  1. Persistence of airline accidents.

    PubMed

    Barros, Carlos Pestana; Faria, Joao Ricardo; Gil-Alana, Luis Alberiko

    2010-10-01

    This paper expands on air travel accident research by examining the relationship between air travel accidents and airline traffic or volume in the period from 1927-2006. The theoretical model is based on a representative airline company that aims to maximise its profits, and it utilises a fractional integration approach in order to determine whether there is a persistent pattern over time with respect to air accidents and air traffic. Furthermore, the paper analyses how airline accidents are related to traffic using a fractional cointegration approach. It finds that airline accidents are persistent and that a (non-stationary) fractional cointegration relationship exists between total airline accidents and airline passengers, airline miles and airline revenues, with shocks that affect the long-run equilibrium disappearing in the very long term. Moreover, this relation is negative, which might be due to the fact that air travel is becoming safer and there is greater competition in the airline industry. Policy implications are derived for countering accident events, based on competition and regulation. © 2010 The Author(s). Journal compilation © Overseas Development Institute, 2010.

  2. Diabetes medication persistence, different medications have different persistence rates.

    PubMed

    Shani, Michal; Lustman, Alex; Vinker, Shlomo

    2017-08-01

    To assess the persistence of diabetic patients to oral medications. The study included all type 2 diabetic patients over 40 years, members of one District of Clalit Health Services Israel, who were diagnosed with diabetes mellitus before 2008 and who filled at least one prescription per year during 2008-2010, for the following medications: metformin, glibenclamide, acarbose, statins, angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor antagonists (ARBs). Purchase of at least 9 monthly prescriptions during 2009 was considered "good medication persistence". We compared HbA1c and LDL levels, according to medication persistence, for each medication; and cross persistence rates between medications. 21,357 patients were included. Average age was 67.0±11.0years, 48.9% were men, and 35.8% were from low SES. Good medication persistence rates for ARBs were 78.8%, ACEI 69.0%, statins 66.6%, acarbose 67.8%, metformin 58.6%, and glibenclamide 55.3%. Good persistence to any of the medications tested was associated with a higher rate of good persistence to other medications. Patients who took more medications had better persistence rates. Different oral medications used by diabetic patients have different persistence rates. Good persistence for any one medication is an indicator of good persistence to other medications. Investment in enhancing medication persistence in persons with diabetes may improve persistence to other medications, as well as improve glycemic control. Copyright © 2017 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  3. Biodegradation of mixed pesticides by mixed pesticide enriched cultures.

    PubMed

    Krishna, K Rama; Philip, Ligy

    2009-01-01

    This paper discusses the degradation kinetics of mixed (lindane, methyl parathion and carbofuran) pesticides by mixed pesticide enriched cultures (MEC) under various environmental conditions. The bacterial strains isolated from the mixed microbial consortium were identified as Pseudomonas aeruginosa (MTCC 9236), Bacillus sp. (MTCC 9235) and Chryseobacterium joostei (MTCC 9237). Batch studies were conducted to estimate the biokinetic parameters like the maximum specific growth rate (mu(max)), Yield Coefficient (Y(T)), half saturation concentration (K(s)) and inhibition concentration (Ki) for individual and mixed pesticide enriched cultures. The cultures enriched in a particular pollutant always showed high growth rate and low inhibition in that particular pollutant compared to MEC. After seven weeks of incubation, mixed pesticide enriched cultures were able to degrade 72% lindane, 95% carbofuran and 100% of methyl parathion in facultative co-metabolic conditions. In aerobic systems, degradation efficiencies of lindane methyl parathion and carbofuran were increased by the addition of 2g L(- 1) of dextrose. Though many metabolic compounds of mixed pesticides were observed at different time intervals, none of the metabolites were persistent. Based on the observed metabolites, a degradation pathway was postulated for different pesticides under various environmental conditions.

  4. Lateral Mixing

    DTIC Science & Technology

    2011-09-30

    ocean as it responds to mesoscale forcing. APPROACH Figure 1: MVP system deployed from stern of R/V Endeavor in Sargasso Sea . My approach for...therefore requires integrative efforts with other sea -going investigators and numerical modelers. The Lateral Mixing Experiment project was an ideal...also participated in the sea -going part of this project, taking my group on the R/V Endeavor in June 2011. Our role was to sample around the center of

  5. Bacterial persistence by RNA endonucleases

    PubMed Central

    Maisonneuve, Etienne; Shakespeare, Lana J.; Jørgensen, Mikkel Girke; Gerdes, Kenn

    2011-01-01

    Bacteria form persisters, individual cells that are highly tolerant to different types of antibiotics. Persister cells are genetically identical to nontolerant kin but have entered a dormant state in which they are recalcitrant to the killing activity of the antibiotics. The molecular mechanisms underlying bacterial persistence are unknown. Here, we show that the ubiquitous Lon (Long Form Filament) protease and mRNA endonucleases (mRNases) encoded by toxin-antitoxin (TA) loci are required for persistence in Escherichia coli. Successive deletion of the 10 mRNase-encoding TA loci of E. coli progressively reduced the level of persisters, showing that persistence is a phenotype common to TA loci. In all cases tested, the antitoxins, which control the activities of the mRNases, are Lon substrates. Consistently, cells lacking lon generated a highly reduced level of persisters. Moreover, Lon overproduction dramatically increased the levels of persisters in wild-type cells but not in cells lacking the 10 mRNases. These results support a simple model according to which mRNases encoded by TA loci are activated in a small fraction of growing cells by Lon-mediated degradation of the antitoxins. Activation of the mRNases, in turn, inhibits global cellular translation, and thereby induces dormancy and persistence. Many pathogenic bacteria known to enter dormant states have a plethora of TA genes. Therefore, in the future, the discoveries described here may lead to a mechanistic understanding of the persistence phenomenon in pathogenic bacteria. PMID:21788497

  6. Caliber-Persistent Artery

    PubMed Central

    Costa, Sabrina Araújo Pinho; Ruiz, Marcelo Martinson; Kaba, Shajadi Pardo; Florezi, Giovanna Piacenza; Lemos Júnior, Celso Augusto; Witzel, Andréa Lusvarghi

    2015-01-01

    Caliber-persistent artery (CPLA) of the lip is a common vascular anomaly in which a main arterial branch extends to the surface of the mucous tissue with no reduction in its diameter. It usually manifests as pulsatile papule, is easily misdiagnosed, and is observed more frequently among older people, suggesting that its development may involve a degenerative process associated with aging; CPLA is also characterized by the loss of tone of the adjacent supporting connective tissue. Although the diagnosis is clinical, high-resolution Doppler ultrasound is a useful noninvasive tool for evaluating the lesion. This report describes the case of a 58-year-old male patient who complained of a lesion of the lower lip with bleeding and recurrent ulceration. The patient was successfully treated in our hospital after a diagnosis of CPLA and is currently undergoing a clinical outpatient follow-up with no complaints. PMID:26448884

  7. New daily persistent headache.

    PubMed

    Tyagi, Alok

    2012-08-01

    New daily persistent headache (NDPH) is a chronic headache developing in a person who does not have a past history of headaches. The headache begins acutely and reaches its peak within 3 days. It is important to exclude secondary causes, particularly headaches due to alterations in cerebrospinal fluid (CSF) pressure and volume. A significant proportion of NDPH sufferers may have intractable headaches that are refractory to treatment. The condition is best viewed as a syndrome rather than a diagnosis. The headache can mimic chronic migraine and chronic tension-type headache, and it is also important to exclude secondary causes, particularly headaches due to alterations in CSF pressure and volume. A large proportion of NDPH sufferers have migrainous features to their headache and should be managed with treatments used for treating migraine. A small group of NDPH sufferers may have intractable headaches that are refractory to treatment.

  8. Persistent Genital Arousal Disorder

    PubMed Central

    Aswath, Manju; Pandit, Lakshmi V.; Kashyap, Karthik; Ramnath, Raguram

    2016-01-01

    Persistent genital arousal disorder (PGAD) is a phenomenon, in which afflicted women experience spontaneous genital arousal, unresolved by orgasms and triggered by sexual or nonsexual stimuli, eliciting stress. The current case is a 40-year-old female who experienced such orgasms for about a month. Physical examination, investigations, and psychological testing were noncontributory. Carbamazepine (600 mg) was discontinued due to a lack of response. She improved significantly with supportive therapy. Various neuropsychological conditions, pelvic pathology, medications, etc., have been associated with this disorder. Pharmacologic strategies have included the use of antidepressants, antipsychotics, mood stabilizers, and analgesics. Validation, psycho-education, identifying triggers, distraction techniques, and pelvic massage have been tried. Living with PGAD is very demanding. There is a lack of understanding of the problem, shame, and hesitation to seek help. The syndrome has been recently described, and understanding is still evolving. PMID:27570347

  9. Persistent Genital Arousal Disorder.

    PubMed

    Aswath, Manju; Pandit, Lakshmi V; Kashyap, Karthik; Ramnath, Raguram

    2016-01-01

    Persistent genital arousal disorder (PGAD) is a phenomenon, in which afflicted women experience spontaneous genital arousal, unresolved by orgasms and triggered by sexual or nonsexual stimuli, eliciting stress. The current case is a 40-year-old female who experienced such orgasms for about a month. Physical examination, investigations, and psychological testing were noncontributory. Carbamazepine (600 mg) was discontinued due to a lack of response. She improved significantly with supportive therapy. Various neuropsychological conditions, pelvic pathology, medications, etc., have been associated with this disorder. Pharmacologic strategies have included the use of antidepressants, antipsychotics, mood stabilizers, and analgesics. Validation, psycho-education, identifying triggers, distraction techniques, and pelvic massage have been tried. Living with PGAD is very demanding. There is a lack of understanding of the problem, shame, and hesitation to seek help. The syndrome has been recently described, and understanding is still evolving.

  10. Persistent Temporal Streams

    NASA Astrophysics Data System (ADS)

    Hilley, David; Ramachandran, Umakishore

    Distributed continuous live stream analysis applications are increasingly common. Video-based surveillance, emergency response, disaster recovery, and critical infrastructure protection are all examples of such applications. They are characterized by a variety of high- and low-bandwidth streams as well as a need for analyzing both live and archived streams. We present a system called Persistent Temporal Streams (PTS) that supports a higher-level, domain-targeted programming abstraction for such applications. PTS provides a simple but expressive stream abstraction encompassing transport, manipulation and storage of streaming data. In this paper, we present a system architecture for implementing PTS. We provide an experimental evaluation which shows the system-level primitives can be implemented in a lightweight and high-performance manner, and an application-based evaluation designed to show that a representative high-bandwidth stream analysis application can be implemented relatively simply and with good performance.

  11. Epigenetic regulation of persistent pain

    PubMed Central

    Bai, Guang; Ren, Ke; Dubner, Ronald

    2014-01-01

    Persistent or chronic pain is tightly associated with various environmental changes and linked to abnormal gene expression within cells processing nociceptive signaling. Epigenetic regulation governs gene expression in response to environmental cues. Recent animal model and clinical studies indicate that epigenetic regulation plays an important role in the development/maintenance of persistent pain and, possibly the transition of acute pain to chronic pain, thus shedding light in a direction for development of new therapeutics for persistent pain. PMID:24948399

  12. Donor Lymphocyte Infusions Used to Treat Mixed-Chimeric and High-Risk Patient Populations in the Relapsed and Nonrelapsed Settings after Allogeneic Transplantation for Hematologic Malignancies Are Associated with High Five-Year Survival if Persistent Full Donor Chimerism Is Obtained or Maintained.

    PubMed

    Caldemeyer, Lauren E; Akard, Luke P; Edwards, John R; Tandra, Anand; Wagenknecht, Dawn R; Dugan, Michael J

    2017-07-13

    Mixed chimerism (MC), a persistent or increasing number of host cells after allogeneic hematopoietic stem cell transplantation (HSCT), is a predictor of disease relapse. Donor lymphocyte infusions (DLI) have the potential to enhance the graft-versus-malignancy (GVM) effect, reducing the risk of relapse in patients with MC. Hence, in addition to utilizing DLI in the relapsed setting, there is a motivation to pursue pre-emptive DLI for patients in complete remissions after HSCT. To assess the safety and efficacy of DLI, records of 86 patients who received DLI between 2003 and 2015 at a single institution were studied retrospectively. Patients who received DLI included 50 patients with relapsed/residual (RR) disease, 29 patients with emerging MC without detectable disease, and 7 patients in an "other" cohort who had neither RR disease nor emerging MC after HSCT. DLI were administered using a dose-escalation protocol. After DLI, 93% of MC patients converted to full donor chimerism (FDC). Nonrelapsed patients (MC and other) reported high overall survival (OS) at 1 and 5 years (83% at 1 year, 70% at 5 years for MC; 86% at 1 year, 69% at 5 years for other) and was statistically superior to 5-year OS for RR patients (nonrelapsed 69% versus RR 28%; P = .00032). Improved survival correlated with successful conversion to FDC after DLI for RR and MC cohorts: 71% 2-year OS for patients converted to FDC versus 13% for patients who failed to achieve FDC (P < .0001). DLI for nonrelapsed patients was associated with a superior 5-year progression-free survival (PFS) of 71% compared with 18% 5-year PFS in the RR group (P < .0001). Relapse/progressive disease was the most frequent cause of death (41%). Seven MC (24%), 2 other (29%), and 39 RR patients (78%) relapsed or did not respond after DLI. Overall, 6 patients (7%) died of graft-versus-host disease after DLI. Our results demonstrate a successful dose-escalation approach for nonrelapsed patients that correlated with

  13. Learning To Persist-Persisting To Learn. Revised Edition.

    ERIC Educational Resources Information Center

    Howard, Bessie C.

    This guide to improving student persistence is the first part of a four-part series addressing the essential characteristics of effective instruction that have a positive impact on the academic achievement of Black and Hispanic students. Persistence is learned behavior, and lower-class students are more likely than middle-class students to observe…

  14. Management of persistent vaginitis.

    PubMed

    Nyirjesy, Paul

    2014-12-01

    With vaginitis remaining a common condition that leads women to seek care, it is not surprising that some women develop chronic vulvovaginal problems that are difficult to diagnose and treat. With a differential diagnosis that encompasses vulvar disorders and infectious and noninfectious causes of vaginitis, accurate diagnosis is the cornerstone of choosing effective therapy. Evaluation should include a symptom-specific history, careful vulvar and vaginal examination, and office-based tests (vaginal pH, amine test, saline and 10% potassium hydroxide microscopy). Ancillary tests, especially yeast culture with speciation, are frequently crucial to obtaining a correct diagnosis. A heavy but normal physiologic discharge can be determined by excluding other causes. With vulvovaginal candidiasis, differentiating between Candida albicans and non-albicans Candida infection has important treatment ramifications. Most patients with C albicans infections can be successfully treated with maintenance antifungal therapy, usually with fluconazole. Although many non-albicans Candida, particularly Candida glabrata, may at times be innocent bystanders, vaginal boric acid therapy is an effective first choice for many true non-albicans Candida infections. Recurrent bacterial vaginosis, a difficult therapeutic challenge, can often be controlled with maintenance therapy. Multiple options, especially high-dose tinidazole, have been used for metronidazole-resistant trichomoniasis. With the aging of the U.S. population, atrophic vaginitis and desquamative inflammatory vaginitis, both associated with hypoestrogenism, are encountered frequently in women with persistent vaginitis.

  15. Isolated persistent hypermethioninemia.

    PubMed Central

    Mudd, S H; Levy, H L; Tangerman, A; Boujet, C; Buist, N; Davidson-Mundt, A; Hudgins, L; Oyanagi, K; Nagao, M; Wilson, W G

    1995-01-01

    New information has been obtained on 30 patients with isolated persistent hypermethioninemia, most of them previously unreported. Biopsies to confirm the presumptive diagnosis of partially deficient activity of ATP: L-methionine S-adenosyltransferase (MAT; E.C.2.5.1.6) in liver were not performed on most of these patients. However, none showed the clinical findings or the extreme elevations of serum folate previously described in other patients with isolated hypermethioninemia considered not to have hepatic MAT deficiency. Patients ascertained on biochemical grounds had no neurological abnormalities, and 27/30 had IQs or Bayley development-index scores within normal limits or were judged to have normal mental development. Methionine transamination metabolites accumulated abnormally only when plasma methionine concentrations exceeded 300-350 microM and did so more markedly after 0.9 years of age. Data were obtained on urinary organic acids as well as plasma creatinine concentrations. Patterns of inheritance of isolated hypermethioninemia were variable. Considerations as to the optimal management of this group of patients are discussed. PMID:7573050

  16. Persistent asymmetrical priority effects in a California grassland restoration experiment.

    PubMed

    Werner, Chhaya M; Vaughn, Kurt J; Stuble, Katharine L; Wolf, Kristina; Young, Truman P

    2016-09-01

    The order of species arrival can dramatically alter the trajectory of community development. While there is experimental evidence that priority effects can be important drivers of community structure early on, the persistence and duration of these effects is unclear. Here we report on a community assembly experiment in which a mix of four native grasses and a mix of four native forbs were planted on their own, together, or with one-year priority over the other guild. We found positive effects of priority for both grasses and forbs in the initial years of the experiment. However, 6-8 yr after planting, the effectiveness of priority treatments were mixed. Some species became rare, persisting only in treatments in which they had been given priority; others continued to maintain high cover and exhibit a strong positive signal of priority effects; still others remained common but no longer showed a signature of the initial priority effects; and finally, some species became locally extinct across all experimental plots. Grass priority over forbs was strong and persistent, but not forb priority over grasses. Our results demonstrate that the long-term benefits of temporal priority can persist for at least 8 yr for some, but not all species, and these continued effects result in distinct community composition. Manipulating the trajectory of community assembly through priority in seeding has potential as a useful tool for restoration. © 2016 by the Ecological Society of America.

  17. Multidimensional persistence in biomolecular data.

    PubMed

    Xia, Kelin; Wei, Guo-Wei

    2015-07-30

    Persistent homology has emerged as a popular technique for the topological simplification of big data, including biomolecular data. Multidimensional persistence bears considerable promise to bridge the gap between geometry and topology. However, its practical and robust construction has been a challenge. We introduce two families of multidimensional persistence, namely pseudomultidimensional persistence and multiscale multidimensional persistence. The former is generated via the repeated applications of persistent homology filtration to high-dimensional data, such as results from molecular dynamics or partial differential equations. The latter is constructed via isotropic and anisotropic scales that create new simiplicial complexes and associated topological spaces. The utility, robustness, and efficiency of the proposed topological methods are demonstrated via protein folding, protein flexibility analysis, the topological denoising of cryoelectron microscopy data, and the scale dependence of nanoparticles. Topological transition between partial folded and unfolded proteins has been observed in multidimensional persistence. The separation between noise topological signatures and molecular topological fingerprints is achieved by the Laplace-Beltrami flow. The multiscale multidimensional persistent homology reveals relative local features in Betti-0 invariants and the relatively global characteristics of Betti-1 and Betti-2 invariants. © 2015 Wiley Periodicals, Inc.

  18. Multidimensional persistence in biomolecular data

    PubMed Central

    Xia, Kelin; Wei, Guo-Wei

    2015-01-01

    Persistent homology has emerged as a popular technique for the topological simplification of big data, including biomolecular data. Multidimensional persistence bears considerable promise to bridge the gap between geometry and topology. However, its practical and robust construction has been a challenge. We introduce two families of multidimensional persistence, namely pseudo-multidimensional persistence and multiscale multidimensional persistence. The former is generated via the repeated applications of persistent homology filtration to high dimensional data, such as results from molecular dynamics or partial differential equations. The latter is constructed via isotropic and anisotropic scales that create new simiplicial complexes and associated topological spaces. The utility, robustness and efficiency of the proposed topological methods are demonstrated via protein folding, protein flexibility analysis, the topological denoising of cryo-electron microscopy data, and the scale dependence of nano particles. Topological transition between partial folded and unfolded proteins has been observed in multidimensional persistence. The separation between noise topological signatures and molecular topological fingerprints is achieved by the Laplace-Beltrami flow. The multiscale multidimensional persistent homology reveals relative local features in Betti-0 invariants and the relatively global characteristics of Betti-1 and Betti-2 invariants. PMID:26032339

  19. Radiological Contaminant Persistence and Decontamination ...

    EPA Pesticide Factsheets

    Report The objective of this study was to use the Pipe Decontamination Experimental Design Protocol (PDEDP) to evaluate the persistence of cesium, cobalt, and strontium on concrete and polyvinyl chloride (PVC) and explore possible decontamination approaches. The PDEDP is an approach for evaluating the persistence characteristics of contaminants on drinking water pipe materials and various decontamination approaches.

  20. Metabolic aspects of bacterial persisters

    PubMed Central

    Prax, Marcel; Bertram, Ralph

    2014-01-01

    Persister cells form a multi-drug tolerant subpopulation within an isogenic culture of bacteria that are genetically susceptible to antibiotics. Studies with different Gram negative and Gram positive bacteria have identified a large number of genes associated with the persister state. In contrast, the revelation of persister metabolism has only been addressed recently. We here summarize metabolic aspects of persisters, which includes an overview about the bifunctional role of selected carbohydrates as both triggers for the exit from the drug tolerant state and metabolites which persisters feed on. Also alarmones as indicators for starvation have been shown to influence persister levels via different signaling cascades involving the activation of toxin-antitoxin systems and other regulatory factors. Finally, recent data obtained by 13C-isotopolog profiling demonstrated an active amino acid anabolism in Staphylococcus aureus cultures challenged with high drug concentrations. Understanding the metabolism of persister cells poses challenges but also paves the way for the development of anti-persister compounds. PMID:25374846

  1. Persistence. Snapshot Report, Fall 2011

    ERIC Educational Resources Information Center

    National Student Clearinghouse, 2011

    2011-01-01

    Today's college student is not your '60s drop-out. In 2010, college students tended to stay enrolled (i.e., persist), even if it was in a different school, according to the National Student Clearinghouse Research Center. For a student enrolled in the fall, persistence is defined as either continued enrollment during the next term after the fall or…

  2. Persistent Criminality and Career Length

    ERIC Educational Resources Information Center

    Haapanen, Rudy; Britton, Lee; Croisdale, Tim

    2007-01-01

    This study is an examination of persistent offending and its implications for the understanding and investigation of desistance and career length. Persistence, especially as it is operationalized using official measures, is characterized as fundamentally a measure of resistance to formal social control: continued crime in the face of increasingly…

  3. Hallucinogen persisting perception disorder after psilocybin consumption: a case study.

    PubMed

    Espiard, Marie-Laure; Lecardeur, Laurent; Abadie, Pascale; Halbecq, Isabelle; Dollfus, Sonia

    2005-08-01

    The recurrence of flashbacks without acute or chronic hallucinogen consumption has been recognized in the DSM IV criteria as the hallucinogen persisting perception disorder (HPPD). Perceptual disturbances may last for 5 years or more and represent a real psychosocial distress. We reported here a case of a 18-year-old young man presenting HPPD after a mixed intoxication with psylocibin and cannabis. This report shows symptomatic recurrences persisting more than 8 months. Various differential diagnoses were evoked and our therapeutic strategies were described.

  4. Persistence, resistance, resonance

    NASA Astrophysics Data System (ADS)

    Tsadka, Maayan

    form of musical consumption and experience. The three pieces draw lines connecting different aspects of persistence, resistance, and resonance.

  5. Energy landscapes and persistent minima

    SciTech Connect

    Carr, Joanne M.; Wales, David J.; Mazauric, Dorian; Cazals, Frédéric

    2016-02-07

    We consider a coarse-graining of high-dimensional potential energy landscapes based upon persistences, which correspond to lowest barrier heights to lower-energy minima. Persistences can be calculated efficiently for local minima in kinetic transition networks that are based on stationary points of the prevailing energy landscape. The networks studied here represent peptides, proteins, nucleic acids, an atomic cluster, and a glassy system. Minima with high persistence values are likely to represent some form of alternative structural morphology, which, if appreciably populated at the prevailing temperature, could compete with the global minimum (defined as infinitely persistent). Threshold values on persistences (and in some cases equilibrium occupation probabilities) have therefore been used in this work to select subsets of minima, which were then analysed to see how well they can represent features of the full network. Simplified disconnectivity graphs showing only the selected minima can convey the funnelling (including any multiple-funnel) characteristics of the corresponding full graphs. The effect of the choice of persistence threshold on the reduced disconnectivity graphs was considered for a system with a hierarchical, glassy landscape. Sets of persistent minima were also found to be useful in comparing networks for the same system sampled under different conditions, using minimum oriented spanning forests.

  6. [MOLECULAR ASPECTS OF BRUCELLA PERSISTENCE].

    PubMed

    Kulakov Yu K

    2016-01-01

    Brucellosis is a dangerous zoonotic disease of animals and humans caused by bacteria of the genus Brucella, which are able to survive, multiply, and persist in host cells. The review is devoted to the Brucella species persistence connected to the molecular mechanisms of escape from innate and adaptive immunity of the host and active interaction of effector proteins of the type IV secretion system with the host's signaling pathways. Understanding of the molecular mechanisms used by Brucella for the intracellular persistence in the host organism can allow us to develop new and effective means for the prevention and treatment of chronic brucellosis infection.

  7. Prenatal diagnosis of persistent cloaca.

    PubMed

    Suzumori, Nobuhiro; Obayashi, Shintaro; Hattori, Yukio; Kaneko, Saori; Suzuki, Yoshikatsu; Sugiura-Ogasawara, Mayumi

    2009-09-01

    We report four cases of persistent cloaca diagnosed at 32-33 weeks of gestation. In cases of persistent cloaca, serial prenatal ultrasonography shows transient fetal ascites, enlarged cystic structures arising from the fetal pelvis. Our four cases of persistent cloaca were diagnosed prenatally. Persistent cloaca should be considered in any female fetus presenting with hydronephrosis and a large cystic lesion arising from the pelvis as assessed by ultrasound and magnetic resonance imaging. Neither pulmonary hypoplasia nor severe oligohydramnios were found in any of our four cases, and they each had a good prognosis. Prenatal diagnosis allows time for parental counseling and delivery planning at a tertiary care center for neonatal intensive care and pediatric surgery.

  8. Immunomodulation by Persistent Organic Pollutants

    EPA Science Inventory

    Persistent organic pollutants (POPs) are widely distnbuted in the environment, are resistant to degradation, and increase in concentration (biomagnify) in the food chain. Concentrations in apical predators may be tens to hundreds of times greater than concentrations in their pref...

  9. Immunomodulation by Persistent Organic Pollutants

    EPA Science Inventory

    Persistent organic pollutants (POPs) are widely distnbuted in the environment, are resistant to degradation, and increase in concentration (biomagnify) in the food chain. Concentrations in apical predators may be tens to hundreds of times greater than concentrations in their pref...

  10. Object-oriented Persistent Homology.

    PubMed

    Wang, Bao; Wei, Guo-Wei

    2016-01-15

    Persistent homology provides a new approach for the topological simplification of big data via measuring the life time of intrinsic topological features in a filtration process and has found its success in scientific and engineering applications. However, such a success is essentially limited to qualitative data classification and analysis. Indeed, persistent homology has rarely been employed for quantitative modeling and prediction. Additionally, the present persistent homology is a passive tool, rather than a proactive technique, for classification and analysis. In this work, we outline a general protocol to construct object-oriented persistent homology methods. By means of differential geometry theory of surfaces, we construct an objective functional, namely, a surface free energy defined on the data of interest. The minimization of the objective functional leads to a Laplace-Beltrami operator which generates a multiscale representation of the initial data and offers an objective oriented filtration process. The resulting differential geometry based object-oriented persistent homology is able to preserve desirable geometric features in the evolutionary filtration and enhances the corresponding topological persistence. The cubical complex based homology algorithm is employed in the present work to be compatible with the Cartesian representation of the Laplace-Beltrami flow. The proposed Laplace-Beltrami flow based persistent homology method is extensively validated. The consistence between Laplace-Beltrami flow based filtration and Euclidean distance based filtration is confirmed on the Vietoris-Rips complex for a large amount of numerical tests. The convergence and reliability of the present Laplace-Beltrami flow based cubical complex filtration approach are analyzed over various spatial and temporal mesh sizes. The Laplace-Beltrami flow based persistent homology approach is utilized to study the intrinsic topology of proteins and fullerene molecules. Based on a

  11. Object-oriented Persistent Homology

    PubMed Central

    Wang, Bao; Wei, Guo-Wei

    2015-01-01

    Persistent homology provides a new approach for the topological simplification of big data via measuring the life time of intrinsic topological features in a filtration process and has found its success in scientific and engineering applications. However, such a success is essentially limited to qualitative data classification and analysis. Indeed, persistent homology has rarely been employed for quantitative modeling and prediction. Additionally, the present persistent homology is a passive tool, rather than a proactive technique, for classification and analysis. In this work, we outline a general protocol to construct object-oriented persistent homology methods. By means of differential geometry theory of surfaces, we construct an objective functional, namely, a surface free energy defined on the data of interest. The minimization of the objective functional leads to a Laplace-Beltrami operator which generates a multiscale representation of the initial data and offers an objective oriented filtration process. The resulting differential geometry based object-oriented persistent homology is able to preserve desirable geometric features in the evolutionary filtration and enhances the corresponding topological persistence. The cubical complex based homology algorithm is employed in the present work to be compatible with the Cartesian representation of the Laplace-Beltrami flow. The proposed Laplace-Beltrami flow based persistent homology method is extensively validated. The consistence between Laplace-Beltrami flow based filtration and Euclidean distance based filtration is confirmed on the Vietoris-Rips complex for a large amount of numerical tests. The convergence and reliability of the present Laplace-Beltrami flow based cubical complex filtration approach are analyzed over various spatial and temporal mesh sizes. The Laplace-Beltrami flow based persistent homology approach is utilized to study the intrinsic topology of proteins and fullerene molecules. Based on a

  12. Object-oriented persistent homology

    NASA Astrophysics Data System (ADS)

    Wang, Bao; Wei, Guo-Wei

    2016-01-01

    Persistent homology provides a new approach for the topological simplification of big data via measuring the life time of intrinsic topological features in a filtration process and has found its success in scientific and engineering applications. However, such a success is essentially limited to qualitative data classification and analysis. Indeed, persistent homology has rarely been employed for quantitative modeling and prediction. Additionally, the present persistent homology is a passive tool, rather than a proactive technique, for classification and analysis. In this work, we outline a general protocol to construct object-oriented persistent homology methods. By means of differential geometry theory of surfaces, we construct an objective functional, namely, a surface free energy defined on the data of interest. The minimization of the objective functional leads to a Laplace-Beltrami operator which generates a multiscale representation of the initial data and offers an objective oriented filtration process. The resulting differential geometry based object-oriented persistent homology is able to preserve desirable geometric features in the evolutionary filtration and enhances the corresponding topological persistence. The cubical complex based homology algorithm is employed in the present work to be compatible with the Cartesian representation of the Laplace-Beltrami flow. The proposed Laplace-Beltrami flow based persistent homology method is extensively validated. The consistence between Laplace-Beltrami flow based filtration and Euclidean distance based filtration is confirmed on the Vietoris-Rips complex for a large amount of numerical tests. The convergence and reliability of the present Laplace-Beltrami flow based cubical complex filtration approach are analyzed over various spatial and temporal mesh sizes. The Laplace-Beltrami flow based persistent homology approach is utilized to study the intrinsic topology of proteins and fullerene molecules. Based on a

  13. Risk factors for persistent diarrhoea.

    PubMed

    Shahid, N S; Sack, D A; Rahman, M; Alam, A N; Rahman, N

    1988-10-22

    With a systematically sampled population of children aged under 5 attending this centre for diarrhoeal disease research during 1983-5 a retrospective analysis of persistent diarrhoea (defined as greater than 14 days' duration) was performed to identify the possible risk factors for this syndrome. Of the 4155 children included in the analysis, 410 (10%) gave a history of persistent diarrhoea. A comparison with children with acute diarrhoea matched for age showed that 11 factors were correlated with persistent diarrhoea, and strongly associated factors were stools with blood or mucus, or both, lower respiratory tract infection, malnutrition, vitamin A deficiency, and antibiotic use before presentation. The peak age was 2 years, and there was no sex difference. Deaths occurred more often in the group with persistent diarrhoea. Although Shigella spp, Campylobacter jejuni, and Giardia lamblia were frequently identified, their rates of isolation were not significantly higher among patients with persistent diarrhoea. No seasonal variation was observed in the rates of persistent diarrhoea. Although the introduction of family food to the diet was associated with higher rates, this factor was difficult to separate from the age dependent risks.

  14. Risk factors for persistent diarrhoea.

    PubMed Central

    Shahid, N. S.; Sack, D. A.; Rahman, M.; Alam, A. N.; Rahman, N.

    1988-01-01

    With a systematically sampled population of children aged under 5 attending this centre for diarrhoeal disease research during 1983-5 a retrospective analysis of persistent diarrhoea (defined as greater than 14 days' duration) was performed to identify the possible risk factors for this syndrome. Of the 4155 children included in the analysis, 410 (10%) gave a history of persistent diarrhoea. A comparison with children with acute diarrhoea matched for age showed that 11 factors were correlated with persistent diarrhoea, and strongly associated factors were stools with blood or mucus, or both, lower respiratory tract infection, malnutrition, vitamin A deficiency, and antibiotic use before presentation. The peak age was 2 years, and there was no sex difference. Deaths occurred more often in the group with persistent diarrhoea. Although Shigella spp, Campylobacter jejuni, and Giardia lamblia were frequently identified, their rates of isolation were not significantly higher among patients with persistent diarrhoea. No seasonal variation was observed in the rates of persistent diarrhoea. Although the introduction of family food to the diet was associated with higher rates, this factor was difficult to separate from the age dependent risks. PMID:3142603

  15. Virologic, Clinical, and Immune Response Outcomes of Patients With Hepatitis C Virus-Associated Cryoglobulinemia Treated With Direct-Acting Antivirals.

    PubMed

    Bonacci, Martín; Lens, Sabela; Londoño, María-Carlota; Mariño, Zoe; Cid, Maria C; Ramos-Casals, Manuel; Sánchez-Tapias, Jose María; Forns, Xavier; Hernández-Rodríguez, José

    2017-04-01

    associated with clinical improvement in most patients with CV. Markers of immune activation, including circulating cryoglobulins, persisted in 52% of patients with CV or ACC, despite a sustained viral response 12 weeks after therapy. A longer follow-up period after viral eradication might be necessary to ensure a normal immune response. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  16. Persistent Diarrhea: A Clinical Review.

    PubMed

    DuPont, Herbert L

    2016-06-28

    Diarrheal disease is commonly encountered in clinical practice. Persistent diarrhea (≥14 days) can be caused by pathogens that differ from those commonly seen in acute illness; proper etiologic diagnosis is important for appropriate therapeutic management. This review provides an overview of the epidemiology, etiology, diagnosis, and management of persistent diarrhea caused by infectious agents in immunocompetent individuals worldwide. Much of the data on persistent diarrhea comes from studies of residents in or expatriates of developing countries and travelers to these regions where follow-up studies have been performed. Persistent diarrhea occurs in approximately 3% of individuals traveling to developing countries. Schistosoma mansoni (and rarely Schistosoma haematobium) intestinal infection is also not very common and is found only in endemic areas. The microbiologic causes of protracted diarrhea include detectable parasitic (eg, Giardia, Cryptosporidium) and bacterial (eg, enteroaggregative Escherichia coli, Shigella) pathogens. Available diagnostic tests include culture-dependent for bacterial pathogens and culture-independent methods for bacterial, viral, and protozoal infections (eg, polymerase chain reaction [PCR]), including multiplex PCR, as well as and microscopy for protozoal infections. Antimicrobial therapy can be given empirically to patients returning from the undeveloped to the developed world. Otherwise, antibiotics should be given based on the results of laboratory testing. Persistent diarrhea is a poorly recognized syndrome in all populations that requires proper assessment and diagnosis to ensure that affected individuals receive the treatment needed to experience improvement of clinical symptoms.

  17. Species Diversity Effects on Productivity, Persistence and Quality of Multispecies Swards in a Four-Year Experiment

    PubMed Central

    Søegaard, Karen; Cong, Wen-Feng; Eriksen, Jørgen

    2017-01-01

    Plant species diversity may benefit natural grassland productivity, but its effect in managed grassland systems is not well understood. A four-year multispecies grassland experiment was conducted to investigate the effect of species diversity–legumes and non-leguminous forbs–on productivity, persistence and sward quality under cutting or grazing regimes and with or without slurry application. Three mixtures were established– 3-mix: grass, red and white clover, 10-mix: 3-mix plus birdsfoot trefoil and six non-leguminous forbs, and 12-mix: 10-mix plus lucerne and festulolium. Species diversity increased sward production and yield persistence under cutting regime. The 12-mix had the highest yield from the second year onwards and no statistically significant yield reduction over four years, while annual yields in the 3-mix and 10-mix decreased significantly with increasing grassland age. The higher yield in the 12-mix was mainly due to the inclusion of high-yielding lucerne. The 10-mix and 12-mix had lower proportions of unsown species than the 3-mix, the difference being dependent on grassland age. Generally, the 3-mix had higher concentrations of in-vitro organic matter digestibility (IVOMD), neutral detergent fiber (NDF) and crude protein (CP), and a lower concentration of ash than the 10-mix and 12-mix. Slurry application increased annual yield production by 10% and changed the botanical composition, increasing the proportion of grass and decreasing the proportion of legumes. Compared to cutting, grazing increased forage production by 9% per cut on average and lowered legume and forb proportions in the mixtures, but yields did not differ among the three mixtures. Overall, our results suggest that species diversity increases sward productivity and persistence only under an ungrazed cutting regime. We conclude that increasing species diversity by selecting appropriate species with compatible management is key to achieving both high yields and high persistence

  18. Student Characteristics, Prior Experiences, and the Perception of Mixed Methods as an Innovation

    ERIC Educational Resources Information Center

    Brown, Sydney E.

    2014-01-01

    There are persistent challenges to teaching mixed methods and innovative solutions are sought in order to address the needs of an increasingly diverse global audience seeking mixed methods instruction. This mixed methods study was conducted to gain insights to course design by more fully understanding the relationships among graduate student…

  19. Student Characteristics, Prior Experiences, and the Perception of Mixed Methods as an Innovation

    ERIC Educational Resources Information Center

    Brown, Sydney E.

    2014-01-01

    There are persistent challenges to teaching mixed methods and innovative solutions are sought in order to address the needs of an increasingly diverse global audience seeking mixed methods instruction. This mixed methods study was conducted to gain insights to course design by more fully understanding the relationships among graduate student…

  20. Energy Savings Lifetimes and Persistence

    SciTech Connect

    Hoffman, Ian M.; Schiller, Steven R.; Todd, Annika; Billingsley, Megan A.; Goldman, Charles A.; Schwartz, Lisa C.

    2016-02-01

    This technical brief explains the concepts of energy savings lifetimes and savings persistence and discusses how program administrators use these factors to calculate savings for efficiency measures, programs and portfolios. Savings lifetime is the length of time that one or more energy efficiency measures or activities save energy, and savings persistence is the change in savings throughout the functional life of a given efficiency measure or activity. Savings lifetimes are essential for assessing the lifecycle benefits and cost effectiveness of efficiency activities and for forecasting loads in resource planning. The brief also provides estimates of savings lifetimes derived from a national collection of costs and savings for electric efficiency programs and portfolios.

  1. Josephson persistent-current qubit

    PubMed

    Mooij; Orlando; Levitov; Tian; van der Wal CH; Lloyd

    1999-08-13

    A qubit was designed that can be fabricated with conventional electron beam lithography and is suited for integration into a large quantum computer. The qubit consists of a micrometer-sized loop with three or four Josephson junctions; the two qubit states have persistent currents of opposite direction. Quantum superpositions of these states are obtained by pulsed microwave modulation of the enclosed magnetic flux by currents in control lines. A superconducting flux transporter allows for controlled transfer between qubits of the flux that is generated by the persistent currents, leading to entanglement of qubit information.

  2. Persistence to antihypertensive drug classes

    PubMed Central

    Qvarnström, Miriam; Kahan, Thomas; Kieler, Helle; Brandt, Lena; Hasselström, Jan; Boström, Kristina Bengtsson; Manhem, Karin; Hjerpe, Per; Wettermark, Björn

    2016-01-01

    Abstract The aim was to study persistence to, and switching between, antihypertensive drug classes and to determine factors associated with poor persistence. This was an observational cohort study. The Swedish Primary Care Cardiovascular Database includes data from medical records, socioeconomic data, filled prescriptions, and hospitalizations from national registries for 75,000 patients with hypertension. Patients included in the study were initiated on antihypertensive drug treatment in primary healthcare in 2006 to 2007. We defined class persistence as the proportion remaining on the initial drug class, including 30 days of gap. Patients with a filled prescription of another antihypertensive drug class after discontinuation of the initial drug, including 30 days of gap, were classified as switchers. Persistence to the various drug classes were compared with that for diuretics. We identified 4997 patients (mean age 60 ± 12 years in men and 63 ± 13 years in women). Out of these, 95 (2%) filled their first prescription for fixed combination therapy and 4902 (98%) for monotherapy, including angiotensin converting enzyme inhibitors (37%), angiotensin receptor blockers (4%), beta blockers (21%), calcium channel blockers (8%), and diuretics (28%). Persistence to the initial drug class was 57% after 1 year and 43% after 2 years. There were no differences in persistence between diuretics and any of the other antihypertensive drug classes, after adjustment for confounders. Discontinuation (all adjusted) was more common in men (P = 0.004), younger patients (P < 0.001), those with mild systolic blood pressure elevation (P < 0.001), and patients born outside the Nordic countries (P < 0.001). Among 1295 patients who switched drug class after their first prescription, only 21% had a blood pressure recorded before the switch occurred; and out them 69% still had high blood pressures. In conclusion, there appears to be no difference in drug class

  3. The Effect of Student Teaching Experiences on the Motivation and Planned Persistence of Pre-Service Teachers

    ERIC Educational Resources Information Center

    Leverett, Avis

    2016-01-01

    This study investigated the motivation to teach and planned persistence of pre-service teachers during two phases of their student teaching experience by using a mixed methods study design. The quantitative design sought to evaluate if the motivation and planned persistence of pre-service teachers changed during the course of the supervised…

  4. The Effect of Student Teaching Experiences on the Motivation and Planned Persistence of Pre-Service Teachers

    ERIC Educational Resources Information Center

    Leverett, Avis

    2016-01-01

    This study investigated the motivation to teach and planned persistence of pre-service teachers during two phases of their student teaching experience by using a mixed methods study design. The quantitative design sought to evaluate if the motivation and planned persistence of pre-service teachers changed during the course of the supervised…

  5. Non-Persisting Student Follow-Up.

    ERIC Educational Resources Information Center

    Willett, Lynn H.

    A survey was conducted to determine the characteristics and opinions of the non-persisting students at Moraine Valley Community College. A random sample of 500 non-persisting students was selected, with equal numbers of full-time and part-time ex-students. Separate questionnaires were used for non-persisting full-time and non-persisting part-time…

  6. Evolutionary dynamics for persistent cooperation in structured populations

    NASA Astrophysics Data System (ADS)

    Li, Yan; Liu, Xinsheng; Claussen, Jens Christian; Guo, Wanlin

    2015-06-01

    The emergence and maintenance of cooperative behavior is a fascinating topic in evolutionary biology and social science. The public goods game (PGG) is a paradigm for exploring cooperative behavior. In PGG, the total resulting payoff is divided equally among all participants. This feature still leads to the dominance of defection without substantially magnifying the public good by a multiplying factor. Much effort has been made to explain the evolution of cooperative strategies, including a recent model in which only a portion of the total benefit is shared by all the players through introducing a new strategy named persistent cooperation. A persistent cooperator is a contributor who is willing to pay a second cost to retrieve the remaining portion of the payoff contributed by themselves. In a previous study, this model was analyzed in the framework of well-mixed populations. This paper focuses on discussing the persistent cooperation in lattice-structured populations. The evolutionary dynamics of the structured populations consisting of three types of competing players (pure cooperators, defectors, and persistent cooperators) are revealed by theoretical analysis and numerical simulations. In particular, the approximate expressions of fixation probabilities for strategies are derived on one-dimensional lattices. The phase diagrams of stationary states, and the evolution of frequencies and spatial patterns for strategies are illustrated on both one-dimensional and square lattices by simulations. Our results are consistent with the general observation that, at least in most situations, a structured population facilitates the evolution of cooperation. Specifically, here we find that the existence of persistent cooperators greatly suppresses the spreading of defectors under more relaxed conditions in structured populations compared to that obtained in well-mixed populations.

  7. Persistent papillomatosis associated with immunodeficiency.

    PubMed

    Duncan, J R; Corbeil, L B; Davies, D H; Schultz, R D; Whitlock, R H

    1975-04-01

    A case report of a young bull with persistent papillomatosis associated with immunodeficiency is presented. Humoral immune responses were normal but cell mediated immunity was deficient. The possible significance of the findings to pathogenesis and therapy of the disease is discussed.

  8. Toward a Persistent Object Base.

    DTIC Science & Technology

    1986-07-01

    toward Improving the practice of software engineering. Such environments provide support for software development, management, and maintenance. There...standardization can all contribute to the openness, In actual practice , of an environment. Integration means that the components of the environment work together...In a persistent obed base, data abstraction should be practiced so that logical concepts are decoupled from physical representations; richer

  9. Persistence Length of Stable Microtubules

    NASA Astrophysics Data System (ADS)

    Hawkins, Taviare; Mirigian, Matthew; Yasar, M. Selcuk; Ross, Jennifer

    2011-03-01

    Microtubules are a vital component of the cytoskeleton. As the most rigid of the cytoskeleton filaments, they give shape and support to the cell. They are also essential for intracellular traffic by providing the roadways onto which organelles are transported, and they are required to reorganize during cellular division. To perform its function in the cell, the microtubule must be rigid yet dynamic. We are interested in how the mechanical properties of stable microtubules change over time. Some ``stable'' microtubules of the cell are recycled after days, such as in the axons of neurons or the cilia and flagella. We measured the persistence length of freely fluctuating taxol-stabilized microtubules over the span of a week and analyzed them via Fourier decomposition. As measured on a daily basis, the persistence length is independent of the contour length. Although measured over the span of the week, the accuracy of the measurement and the persistence length varies. We also studied how fluorescently-labeling the microtubule affects the persistence length and observed that a higher labeling ratio corresponded to greater flexibility. National Science Foundation Grant No: 0928540 to JLR.

  10. Visual Persistence and Adult Dyslexia.

    ERIC Educational Resources Information Center

    Winters, Roberta L.; And Others

    1989-01-01

    Visual persistence was investigated in adults with and without dyslexia in order to determine whether dyslexic adults demonstrate problems similar to those found in childhood dyslexia. Results showed that sensitivity of dyslexic adults was impaired when parts of a test stimulus were presented to adjacent retinal areas, suggesting that under…

  11. Rhinophototherapy in persistent allergic rhinitis.

    PubMed

    Bella, Zsolt; Kiricsi, Ágnes; Viharosné, Éva Dósa-Rácz; Dallos, Attila; Perényi, Ádám; Kiss, Mária; Koreck, Andrea; Kemény, Lajos; Jóri, József; Rovó, László; Kadocsa, Edit

    2017-03-01

    Previous published results have revealed that Rhinolight(®) intranasal phototherapy is safe and effective in intermittent allergic rhinitis. The present objective was to assess whether phototherapy is also safe and effective in persistent allergic rhinitis. Thirty-four patients with persistent allergic rhinitis were randomized into two groups; twenty-five subjects completed the study. The Rhinolight(®) group was treated with a combination of UV-B, UV-A, and high-intensity visible light, while the placebo group received low-intensity visible white light intranasal phototherapy on a total of 13 occasions in 6 weeks. The assessment was based on the diary of symptoms, nasal inspiratory peak flow, quantitative smell threshold, mucociliary transport function, and ICAM-1 expression of the epithelial cells. All nasal symptom scores and nasal inspiratory peak flow measurements improved significantly in the Rhinolight(®) group relative to the placebo group and this finding persisted after 4 weeks of follow-up. The smell and mucociliary functions did not change significantly in either group. The number of ICAM-1 positive cells decreased non-significantly in the Rhinolight(®) group. No severe side-effects were reported during the treatment period. These results suggest that Rhinolight(®) treatment is safe and effective in persistent allergic rhinitis.

  12. Retrospection and Persistent School Absenteeism.

    ERIC Educational Resources Information Center

    Reid, Ken

    1983-01-01

    This paper presents and discusses data based on the perceptions of 128 persistent school absentees on their initial and continued reasons for missing school. The findings suggest that a greater proportion of the students were inclined to blame their institutions, rather than social or psychological factors, for their behavior. (SSH)

  13. Lactobacillus Strain Ecology and Persistence within Broiler Chickens Fed Different Diets: Identification of Persistent Strains ▿ †

    PubMed Central

    Stephenson, David P.; Moore, Robert J.; Allison, Gwen E.

    2010-01-01

    Lactobacilli are autochthonous residents in the chicken gastrointestinal tract, where they may potentially be used as probiotics, competitive exclusion agents, or delivery vehicles. The aim of this study was to use an in vivo model to investigate the effect of diet and competing lactic acid bacteria on the colonization of inoculated Lactobacillus strains, with the goal of identifying strains which can consistently colonize or persist for an extended period of several weeks. Chicken-derived Lactobacillus strains were genetically marked with rifampin resistance and administered on day 0 to chickens fed either a normal commercial diet or a specially formulated high-protein diet. Chickens fed the high-protein diet were also coinoculated with two different mixes of additional lactic acid bacteria. Enterobacterial repetitive intergenic consensus sequence-based PCR (ERIC-PCR) was used to identify rifampin-resistant isolates recovered from chickens. Three strains, belonging to the species Lactobacillus agilis, Lactobacillus crispatus, and Lactobacillus vaginalis, were commonly reisolated from the chickens on both diets at days 21 and 42. The ability of these strains to persist was confirmed in a second chicken trial. All three strains persisted throughout the production period in the chickens fed a commercial diet, while only the L. agilis and L. vaginalis strains persisted in the chickens fed the high-protein diet. In both in vivo trials, competing lactic acid bacteria modified representation of the strains recovered, with all three stains capable of competing in the presence of one or both mixes of coinoculated strains. The in vivo model successfully identified three persistent strains that will be characterized further. PMID:20693442

  14. Mixed connective tissue disease.

    PubMed

    Gunnarsson, Ragnar; Hetlevik, Siri Opsahl; Lilleby, Vibke; Molberg, Øyvind

    2016-02-01

    The concept of mixed connective tissue disease (MCTD) as a separate connective tissue disease (CTD) has persisted for more than four decades. High titers of antibodies targeting the U1 small nuclear ribonucleoprotein particle (U1 snRNP) in peripheral blood are a sine qua non for the diagnosis of MCTD, in addition to distinct clinical features including Raynaud's phenomenon (RP), "puffy hands," arthritis, myositis, pleuritis, pericarditis, interstitial lung disease (ILD), and pulmonary hypertension (PH). Recently, population-based epidemiology data from Norway estimated the point prevalence of adult-onset MCTD to be 3.8 per 100,000 and the mean annual incidence to be 2.1 per million per year, supporting the notion that MCTD is the least common CTD. Little is known about the etiology of MCTD, but recent genetic studies have confirmed that MCTD is a strongly HLA (​human leukocyte antigen)-linked disease, as the HLA profiles of MCTD differ distinctly from the corresponding profiles of ethnically matched healthy controls and other CTDs. In the first section of this review, we provide an update on the clinical, immunological, and genetic features of MCTD and discuss the relationship between MCTD and the other CTDs. Then we proceed to discuss the recent advances in therapy and our current understanding of prognosis and prognostic factors, especially those that are associated with the more serious pulmonary and cardiovascular complications of the disease. In the final section, we discuss some of the key, unresolved questions related to anti-RNP-associated diseases and indicate how these questions may be approached in future studies.

  15. Screening of variants for lactase persistence/non-persistence in populations from South Africa and Ghana

    PubMed Central

    Torniainen, Suvi; Parker, M Iqbal; Holmberg, Ville; Lahtela, Elisa; Dandara, Collet; Jarvela, Irma

    2009-01-01

    Background Lactase non-persistence is a condition where lactase activity is decreased in the intestinal wall after weaning. In European derived populations a single nucleotide polymorphism (SNP) C/T-13910 residing 13.9 kb upstream from the lactase gene has been shown to define lactase activity, and several other single nucleotide polymorphisms (G/C-14010 T/G-13915, C/G-13907 and T/C-13913) in the same region have been identified in African and Middle East populations. Results The T-13910 allele most common in European populations was present in 21.8% mixed ancestry (N = 62) individuals and it was absent in the Xhosa (N = 109) and Ghana (N = 196) subjects. Five other substitutions were also found in the region covering the previously reported variants in African and Middle East populations. These included the G/C-14010 variant common in Kenyan and Tanzanian populations, which was present in 12.8% of Xhosa population and in 8.1% of mixed ancestry subjects. Two novel substitutions (C/T-14091 and A/C-14176) and one previously reported substitution G/A-13937 (rs4988234) were less common and present only in the Xhosa population. One novel substitution G/A-14107 was present in the Xhosa and Ghanaian populations. None of the other previously reported variants were identified. Conclusion Identification of the G/C-14010 variant in the Xhosa population, further confirms their genetic relatedness to other nomadic populations members that belong to the Bantu linguistic group in Tanzania and Kenya. Further studies are needed to confirm the possible relationship of the novel substitutions to the lactase persistence trait. PMID:19575818

  16. Task persistence predicts smoking cessation in smokers with and without schizophrenia.

    PubMed

    Steinberg, Marc L; Williams, Jill M; Gandhi, Kunal K; Foulds, Jonathan; Epstein, Elizabeth E; Brandon, Thomas H

    2012-12-01

    Smokers attempting to quit should benefit from persisting in cognitive and behavioral coping in order to achieve and maintain abstinence. Task persistence, which describes the act of persisting in a difficult or effortful task, is likely to be required in the face of distressing smoking cues, urges to smoke, or other nicotine withdrawal symptoms. This study examined whether task persistence (also called distress tolerance) could prospectively predict smoking cessation in a mixed sample of smokers with and without schizophrenia. Smokers with schizophrenia or schizoaffective disorder (n = 71) and nonpsychiatric smokers (n = 78) seeking treatment at state-funded tobacco dependence treatment clinics completed tests of task persistence before their target quit date, and then provided tobacco use data over the 6 months after their quit date. Findings from generalized estimating equations support the hypothesis that task persistence as measured by a mirror-tracing task predicts smoking cessation while controlling for important covariates such as psychiatric diagnosis, nicotine dependence, and confidence in ability to quit. These findings add to the literature by corroborating reports suggesting that task persistence may make important contributions to smoking cessation success, and by indicating that the contribution of task persistence to smoking cessation is similar for smokers with schizophrenia and nonpsychiatric smokers. These results suggest that efforts to target task persistence in smoking cessation counseling protocols may be warranted.

  17. Task Persistence Predicts Smoking Cessation in Smokers with and without Schizophrenia

    PubMed Central

    Steinberg, Marc L.; Williams, Jill M.; Gandhi, Kunal K.; Foulds, Jonathan; Epstein, Elizabeth E.; Brandon, Thomas H.

    2013-01-01

    Smokers attempting to quit should benefit from persisting in cognitive and behavioral coping in order to achieve and maintain abstinence. Task persistence, which describes the act of persisting in a difficult or effortful task, is likely to be required in the face of distressing smoking cues, urges to smoke, or other nicotine withdrawal symptoms. Objective This study sought to examine whether task persistence (also called distress tolerance) could prospectively predict smoking cessation in a mixed sample of smokers with and without schizophrenia. Method Smokers with schizophrenia or schizoaffective disorder (SZ) (N=71) and non-psychiatric smokers (N=78) seeking treatment at state-funded tobacco dependence treatment clinics completed tests of task persistence before their target quit date (QD), and then provided tobacco use data over the 6-months after their QD. Results Findings from generalized estimating equations (GEE) support the hypothesis that task persistence as measured by a mirror tracing task predicts smoking cessation while controlling for important covariates such as psychiatric diagnosis, nicotine dependence, and confidence in ability to quit. Conclusions These findings add to the literature by corroborating reports suggesting that task persistence may make important contributions to smoking cessation success, and by indicating that the contribution of task persistence to smoking cessation is similar for smokers with schizophrenia and non-psychiatric smokers. These results suggest that efforts to target task persistence in smoking cessation counseling protocols may be warranted. PMID:22642860

  18. Persistent Monitoring Platforms Final Report

    SciTech Connect

    Bennett, C L

    2007-02-22

    This project was inspired and motivated by the need to provide better platforms for persistent surveillance. In the years since the inception of this work, the need for persistence of surveillance platforms has become even more widely appreciated, both within the defense community and the intelligence community. One of the most demanding technical requirements for such a platform involves the power plant and energy storage system, and this project concentrated almost exclusively on the technology associated with this system for a solar powered, high altitude, unmanned aircraft. An important realization for the feasibility of such solar powered aircraft, made at the outset of this project, was that thermal energy may be stored with higher specific energy density than for any other known practical form of rechargeable energy storage. This approach has proved to be extraordinarily fruitful, and a large number of spin-off applications of this technology were developed in the course of this project.

  19. Does persisting fear sustain catatonia?

    PubMed

    Fink, M; Shorter, E

    2017-11-01

    To examine the psychological substrate of catatonia. Reviewing the historical descriptions and explanations of catatonic behaviours by clinicians from its delineation in the 19th century to the present. Patients with catatonia are often haunted by fears and terrors; this has not been widely appreciated, and certainly was lost from view in the days when catatonia was considered a subtype of schizophrenia. The report contributes to resolving a major question in catatonia: is the mind in stupor inactive, as the blank state that we picture in anesthetized patients, or is the mind active, so preoccupied as to exclude all other influences. Persistent fear occupies the mind of catatonic patients. The signs of catatonia are adaptations to persistent fear, akin to tonic immobilization. The relief afforded by sedation supports this interpretation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Persistent Identifiers Implementation in EOSDIS

    NASA Technical Reports Server (NTRS)

    Ramapriyan, H. K. " Rama"

    2016-01-01

    This presentation provides the motivation for and status of implementation of persistent identifiers in NASA's Earth Observation System Data and Information System (EOSDIS). The motivation is provided from the point of view of long-term preservation of datasets such that a number of questions raised by current and future users can be answered easily and precisely. A number of artifacts need to be preserved along with datasets to make this possible, especially when the authors of datasets are no longer available to address users questions. The artifacts and datasets need to be uniquely and persistently identified and linked with each other for full traceability, understandability and scientific reproducibility. Current work in the Earth Science Data and Information System (ESDIS) Project and the Distributed Active Archive Centers (DAACs) in assigning Digital Object Identifiers (DOI) is discussed as well as challenges that remain to be addressed in the future.

  1. Search along persistent random walks

    NASA Astrophysics Data System (ADS)

    Friedrich, Benjamin M.

    2008-06-01

    Optimal search strategies and their implementations in biological systems are a subject of active research. Here we study a search problem which is motivated by the hunt of sperm cells for the egg. We ask for the probability for an active swimmer to find a target under the condition that the swimmer starts at a certain distance from the target. We find that success probability is maximal for a certain level of fluctuations characterized by the persistence length of the swimming path of the swimmer. We derive a scaling law for the optimal persistence length as a function of the initial target distance and search time by mapping the search on a polymer physics problem.

  2. Persistent Patterns in Accretion Disks

    SciTech Connect

    Amin, Mustafa A.; Frolov, Andrei V.; /KIPAC, Menlo Park

    2006-04-03

    We present a set of new characteristic frequencies associated with accretion disks around compact objects. These frequencies arise from persistent rotating patterns in the disk that are finite in radial extent and driven purely by the gravity of the central body. Their existence depends on general relativistic corrections to orbital motion and, if observed, could be used to probe the strong gravity region around a black hole. We also discuss a possible connection to the puzzle of quasi-periodic oscillations.

  3. Persistent asymmetry in the paleomagnetic vector field

    NASA Astrophysics Data System (ADS)

    Love, J. J.

    2001-12-01

    Representing paleomagnetic vectors by a probability density function in a Cartesian three-space of orthogonal, magnetic-field components consisting of a single (unimodal), non-zero mean symmetrical Gaussian function, we can, using a method previously outlined by Love & Constable, estimate the full vectorial mean and variance of the magnetic field at a particular site, and of a particular polarity, even when the data consist of a mixture of directions and intensities. To avoid sampling bias, we restrict our analysis to the 780 kyrs of the Brunhes, and we inspect published data from Hawaii, Mexico, and Réunion, which because of their geographic locations, allow for checks of field symmetry. Comparing our results with published statistical models of the nontransitional mean field and secular variation, we find that the fits are generally inadequate. We conclude that statistically significant mean anomalies, as well as geographic differences in secular variation, require nonzonal terms in a spherical harmonic models of the field. These observations, together with previous work indicating that the mean paleomagnetic field is predominantly a mixture of axial dipolar and quadrupolar ingredients, demonstrate that the mean field and secular variation are asymmetric with respect to the equatorial plane and with respect to longitude. Some of these observations may be due to persistent asymmetry brought about by mixed-parity dynamo states, but they probably also indicate coupling involving lateral heterogeneities at the core-mantle.

  4. Ocean Freshwater Lenses: Prevalence and Persistence

    NASA Astrophysics Data System (ADS)

    Schanze, Julian; Lagerloef, Gary; Schmitt, Raymond

    2017-04-01

    During the Salinity Processes in the Upper Ocean Regional Study II (SPURS-II), a novel dataset was collected from an underway system sampling seawater at the surface, 2m, 3m and 5m. The surface measurements are performed using a boom-mounted suction hose and a peristaltic pump, as well as a shipboard apparatus with multiple de-bubbling stages. The data collected during this cruise reveal approximately fifty freshwater lenses in the Intertropical Convergence Zone (ITCZ), sampled between August 15 and September 20 under several different wind- and precipitation-regimes. Preliminary analysis shows that that the persistence of oceanic freshwater lenses is strongly dependent on the evolution of wind speed as well as the total amount of precipitated water. The results are analyzed in a number of case studies of different types of freshwater lenses, in which the balance between precipitation and wind-driven mixing is elucidated. While the limited sample size restricts the validity of the findings to the SPURS-II region, centered around 125°W, 10°N, during the late boreal summer of 2016, it has important consequences for modelling of freshwater lenses and their impact on satellite retrievals of salinity.

  5. Dealing with Persistent Pain in Older Adults

    MedlinePlus

    ... Related Topics Arthritis Cancer COPD Diabetes Joint Problems Pain Management Related Documents PDF Dealing with Persistent Pain in ... provider may also refer you to a special pain management center. Some persistent pain problems are very complex ...

  6. MOOCs and Persistence: Definitions and Predictors

    ERIC Educational Resources Information Center

    Evans, Brent J.; Baker, Rachel B.

    2016-01-01

    The chapter argues for redefining the term "persistence" as it relates to MOOCs and considers how different measures produce different results in the research; it closes with a review of research on persistence in MOOCs.

  7. Divergence in sink contributions to population persistence

    EPA Science Inventory

    Population sinks present unique conservation challenges. The loss of animals in sinks can compromise persistence. Conversely, sinks can bolster population sizes, improving viability. To assess the contribution of sinks to regional persistence, we simulated the removal of sink hab...

  8. High Persister Mutants in Mycobacterium tuberculosis

    PubMed Central

    Torrey, Heather L.; Keren, Iris; Via, Laura E.; Lee, Jong Seok; Lewis, Kim

    2016-01-01

    Mycobacterium tuberculosis forms drug-tolerant persister cells that are the probable cause of its recalcitrance to antibiotic therapy. While genetically identical to the rest of the population, persisters are dormant, which protects them from killing by bactericidal antibiotics. The mechanism of persister formation in M. tuberculosis is not well understood. In this study, we selected for high persister (hip) mutants and characterized them by whole genome sequencing and transcriptome analysis. In parallel, we identified and characterized clinical isolates that naturally produce high levels of persisters. We compared the hip mutants obtained in vitro with clinical isolates to identify candidate persister genes. Genes involved in lipid biosynthesis, carbon metabolism, toxin-antitoxin systems, and transcriptional regulators were among those identified. We also found that clinical hip isolates exhibited greater ex vivo survival than the low persister isolates. Our data suggest that M. tuberculosis persister formation involves multiple pathways, and hip mutants may contribute to the recalcitrance of the infection. PMID:27176494

  9. PERSISTENT CONTAMINANTS: NEW PRIORITIES, NEW CONCERNS

    EPA Science Inventory


    The Stockholm Convention on persistent organic pollutants (POPs) was adopted in 2001 to protect human health and the environment from chemicals that are highly toxic, persistent, bioaccumulative, and undergo long range transport. These POPs include 9 pesticides, polychlorin...

  10. PERSISTENT CONTAMINANTS: NEW PRIORITIES, NEW CONCERNS

    EPA Science Inventory


    The Stockholm Convention on persistent organic pollutants (POPs) was adopted in 2001 to protect human health and the environment from chemicals that are highly toxic, persistent, bioaccumulative, and undergo long range transport. These POPs include 9 pesticides, polychlorin...

  11. MOOCs and Persistence: Definitions and Predictors

    ERIC Educational Resources Information Center

    Evans, Brent J.; Baker, Rachel B.

    2016-01-01

    The chapter argues for redefining the term "persistence" as it relates to MOOCs and considers how different measures produce different results in the research; it closes with a review of research on persistence in MOOCs.

  12. Bilateral persistent pupillary membranes associated with cataract

    PubMed Central

    Ahmad, Syed Shoeb; Binson, Caroline; Lung, Chong Ka; Ghani, Shuaibah Abdul

    2011-01-01

    Summary Exuberant persistent pupillary membranes (PPM) are rare in adult eyes. We report the case of a 53-year-old man diagnosed with bilateral, profuse, persistent pupillary membranes and unilateral cataract. PMID:23362401

  13. Divergence in sink contributions to population persistence

    EPA Science Inventory

    Population sinks present unique conservation challenges. The loss of animals in sinks can compromise persistence. Conversely, sinks can bolster population sizes, improving viability. To assess the contribution of sinks to regional persistence, we simulated the removal of sink hab...

  14. Persistence-Retention. Snapshot™ Report, Spring 2014

    ERIC Educational Resources Information Center

    National Student Clearinghouse, 2014

    2014-01-01

    This snapshot report provides information on student persistence and retention rates for Spring 2014. Data is presented in tabular format on the following: (1) First-Year Persistence and Retention Rates by Starting Enrollment Intensity (all institutional sectors); (2) First-Year Persistence and Retention Rates by Age at College Entry (all…

  15. Persistence-Retention. Snapshot™ Report, Spring 2015

    ERIC Educational Resources Information Center

    National Student Clearinghouse, 2015

    2015-01-01

    This Snapshot Report offers information on student persistence and retention rates for 2009-2013. It offers data on the following: (1) First-Year Persistence and Retention Rates for Students Who Start College at Four-Year Private Nonprofit Institutions; (2) First-Year Persistence and Retention Rates for Students Who Start College at Four-Year…

  16. The Extraction of Information From Visual Persistence

    ERIC Educational Resources Information Center

    Erwin, Donald E.

    1976-01-01

    This research sought to distinguish among three concepts of visual persistence by substituting the physical presence of the target stimulus while simultaneously inhibiting the formation of a persisting representation. Reportability of information about the stimuli was compared to a condition in which visual persistence was allowed to fully develop…

  17. The Extraction of Information From Visual Persistence

    ERIC Educational Resources Information Center

    Erwin, Donald E.

    1976-01-01

    This research sought to distinguish among three concepts of visual persistence by substituting the physical presence of the target stimulus while simultaneously inhibiting the formation of a persisting representation. Reportability of information about the stimuli was compared to a condition in which visual persistence was allowed to fully develop…

  18. A Grounded Theory of Adult Student Persistence

    ERIC Educational Resources Information Center

    Capps, Rosemary

    2010-01-01

    This grounded theory study investigates adult student persistence at a community college. Student persistence in college is a prerequisite for degree achievement, which correlates with higher earnings and overall better quality of life. Persistence rates remain low for adult students, who combine their college endeavors with responsibilities to…

  19. Intent to Persist at Religiously Affiliated Universities

    ERIC Educational Resources Information Center

    Sansom, J. Mel

    2012-01-01

    The purpose of the secondary data analysis was to examine the attributes of students who intend to persist at the same religiously affiliated institution. The review of literature indicated that persistence has been studied extensively, but there has been only limited investigation of persistence focused on religiously affiliated institutions. The…

  20. Persistence with statin therapy in Hungary

    PubMed Central

    Kiss, Zoltan; Nagy, Laszlo; Reiber, Istvan; Paragh, György; Molnar, Mark Peter; Rokszin, György; Abonyi-Toth, Zsolt

    2013-01-01

    Introduction Persistence with lipid-lowering drug therapy by cardiovascular patients in Hungary has not been studied previously. This study was designed to determine the rate with which Hungarian patients with hyperlipidemia persist in taking lipid-lowering agents, and to compare this with rates reported from other countries. Material and methods This was a retrospective study that utilized data from the Institutional Database of the National Health Insurance Fund to analyze persistence rates with statins and ezetimibe. The study included data for patients who started lipid-lowering therapy between January 1, 2007, and March 31, 2009. Variables included type of lipid-lowering therapy, year of therapy start, and patient age. Main outcome measures were medians of persistence in months, percentages of patients persisting in therapy for 6 and 12 months, and Kaplan-Meier persistence plots. Results The percentage of patients who persisted with overall statin therapy was 46% after 1 month, 40.3% after 2 months, 27% after 6 months, and 20.1% after 12 months. Persistence was slightly greater for statin therapy started during 2008 than during 2007. Older patients were more persistent with therapy than younger patients. Persistence with the combination of ezetimibe-statin therapy was greater than with statin or ezetimibe monotherapy. Conclusions Persistence with statin therapy by patients in Hungary was low compared with other countries. Low persistence may have negated potential clinical benefits of long-term statin therapy. PMID:23847660

  1. Mixing in explosions

    SciTech Connect

    Kuhl, A.L.

    1993-12-01

    Explosions always contain embedded turbulent mixing regions, for example: boundary layers, shear layers, wall jets, and unstable interfaces. Described here is one particular example of the latter, namely, the turbulent mixing occurring in the fireball of an HE-driven blast wave. The evolution of the turbulent mixing was studied via two-dimensional numerical simulations of the convective mixing processes on an adaptive mesh. Vorticity was generated on the fireball interface by baroclinic effects. The interface was unstable, and rapidly evolved into a turbulent mixing layer. Four phases of mixing were observed: (1) a strong blast wave phase; (2) and implosion phase; (3) a reshocking phase; and (4) an asymptotic mixing phase. The flowfield was azimuthally averaged to evaluate the mean and r.m.s. fluctuation profiles across the mixing layer. The vorticity decayed due to a cascade process. This caused the corresponding enstrophy parameter to increase linearly with time -- in agreement with homogeneous turbulence calculations of G.K. Batchelor.

  2. Mixing in astrophysics

    SciTech Connect

    Fryer, Christopher Lee

    2011-01-07

    Turbulent mixing plays a vital role in many fields in astronomy. Here I review a few of these sites, discuss the importance of this turbulent mixing and the techniques used by astrophysicists to solve these problems.

  3. Cold urticaria with persistent weals.

    PubMed

    Juhlin, L

    1981-06-01

    A patient with cold urticaria is described in whom weals appeared immediately after an ice cube test for 3 min and persisted for a week as a red, tender swelling. The duration of the oedema was dependent on the intensity of the immediate reaction. If the immediate wealing was blocked by treatment with an oral antihistamine 3 h before the ice cube test, no delayed reaction was seen. Antihistamines given after the immediate wealing had occurred did not influence the delayed reaction. Reactions to intradermally injected histamine, prostaglandin E, kallikrein, serotonin and serum appeared normal.

  4. Safe and Efficient Persistent Heaps.

    DTIC Science & Technology

    1995-12-01

    Safe and Efficient Persistent Heaps Scott M. Nettles December 1995 CMU-CS-95-225 KSS© 1 «S’S SO- 1 -""-«« -’ i , School of Computer...under grant F33615-93- 1 -1330. The US Government is authorized to reproduce and distribute reprints for Government purposes, notwithstanding any...Contents I Design and Implementation 1 1 Introduction 3 1.1 Safety 4 1.1.1 Transactions 5 1.1.2 Garbage Collection 6 1.1.3 Orthogonal

  5. Mixed methods research.

    PubMed

    Halcomb, Elizabeth; Hickman, Louise

    2015-04-08

    Mixed methods research involves the use of qualitative and quantitative data in a single research project. It represents an alternative methodological approach, combining qualitative and quantitative research approaches, which enables nurse researchers to explore complex phenomena in detail. This article provides a practical overview of mixed methods research and its application in nursing, to guide the novice researcher considering a mixed methods research project.

  6. Behavior and persistence of spilled oil on shoreline

    SciTech Connect

    Michel, J. )

    1991-03-01

    Recent oil spills have re-demonstrated the range of shoreline impacts that are possible from medium to large spills in the United States, i.e., the Exxon Valdez spill which significantly contaminated over 1000 km of shoreline in Alaska and the Mega Borg, which resulted in widely scattered tar balls over a small area. Immediate and total removal of stranded oil should not always be the primary objective. Instead, shoreline cleanup strategies developed for oil spills need to consider the persistence and short- to long-term persistence of stranded oil. There are several general guidelines on the persistence of stranded oil. High-energy shorelines are rapidly and effectively cleaned by natural processes, although there are micro-environments where oil tends to persist (wave shadows, supratidal zone, rock crevices, etc.). On sand and mixed sand and gravel beaches, oil tends to be buried below clean layers of sediment, but erosional/depositional cycles will result in oil removal, usually within one year. In sheltered environments (wetlands, tidal flats) oil will persist for long periods; therefore, oil removal is frequently required, though it is usually poorly implemented. Cobble/boulder beaches, while usually very complex, present a special problem. They can be found in a range of energy settings, with years between periods of storm activity. These beaches can hold large volumes of oil; they can be a source of long-term ({gt} one year) leaching and sheening; subsurface oil is very difficult to remove by surface treatment methods; and they have poorly understood sedimentation patterns, so it is difficult to predict rates of sediment reworking. Studies of recent oil spills have shown a need for shoreline-specific technologies for these types of beaches.

  7. Persistent ENSO in different climates?

    NASA Astrophysics Data System (ADS)

    Fedorov, A. V.; Manucharyan, G. E.

    2013-12-01

    Growing evidence suggests that, despite profound changes in tropical climate, ENSO has been active over a vast geological epoch stretching millions of years from the Late Cretaceous through the Holocene. In particular, ENSO persisted during the Pliocene when there occurred a dramatic reduction in the mean east-west temperature gradient in the equatorial Pacific - a key element of tropical dynamics. Here we use a comprehensive climate model to explore the dependence of ENSO on this temperature gradient. We find that in a broad range of climates ENSO remains surprisingly robust. When the east-west temperature gradient is reduced from 6oC to 1oC, the amplitude of ENSO decreases only by 30-40%, its dominant period remains close to 3-4 years, and the spectral peak stays above red noise. To explain these results we assess the magnitude of ocean-atmosphere feedbacks that control the stability of the natural mode of ENSO (the Bjerknes Index). We find that due to reorganization of the atmospheric Walker circulation in response to changes in the mean temperature gradient, the growth/decay rates of the ENSO mode stay nearly constant throughout different climates. This factor explains the persistence of the Southern Oscillation in past geological epochs and reconciles the seemingly contradictory findings of ENSO occurrence and the small east-west temperature gradient during the Pliocene. Finally, our results explain why ENSO in many climate models seems to be controlled by a weakly-damped mode just below neutral stability.

  8. Persistence of random walk records

    NASA Astrophysics Data System (ADS)

    Ben-Naim, E.; Krapivsky, P. L.

    2014-06-01

    We study records generated by Brownian particles in one dimension. Specifically, we investigate an ordinary random walk and define the record as the maximal position of the walk. We compare the record of an individual random walk with the mean record, obtained as an average over infinitely many realizations. We term the walk ‘superior’ if the record is always above average, and conversely, the walk is said to be ‘inferior’ if the record is always below average. We find that the fraction of superior walks, S, decays algebraically with time, S ˜ t-β, in the limit t → ∞, and that the persistence exponent is nontrivial, β = 0.382 258…. The fraction of inferior walks, I, also decays as a power law, I ˜ t-α, but the persistence exponent is smaller, α = 0.241 608…. Both exponents are roots of transcendental equations involving the parabolic cylinder function. To obtain these theoretical results, we analyze the joint density of superior walks with a given record and position, while for inferior walks it suffices to study the density as a function of position.

  9. Persistence of solar wind features

    NASA Technical Reports Server (NTRS)

    Rucker, H. O.; Rabl, G. K. F.; Desch, M. D.

    1986-01-01

    Using data from the plasma and magnetometer experiments on board the Voyagers 1 and 2 during the approach to Jupiter, solar wind persistence is investigated over the period from January 1978 (Voyager 1 passing by Voyager 2) through February 1979. The trajectories of both spacecraft provided a unique opportunity to study the radial evolution and variation of the solar wind over about 3 AU, and to analyze the persistence of solar wind features along the radially increasing separation distance of both Voyagers. Some emphasis is placed on a period of DOY (day of year) 152 through 212, 1978, in which the observed propagation delay time of solar wind signatures between both Voyagers significantly deviates from the expected delay time. A decrease in the correlation coefficient of the corresponding Voyager 1 and 2 data profiles indicates a remarkable change of the solar wind flow. This period in question coincides to a great extent with the interval V of June-July 1978, selected by STIP (Study of Travelling Interplanetary Phenomena).

  10. An Examination of First-to Second-Year Persistence of First-Generation College Students

    ERIC Educational Resources Information Center

    Guyer, Kimberly Denise

    2013-01-01

    This dissertation uses a mixed-methods design to examine persistence into the second year by students' parental education level. The institution selected for this dissertation is Temple University, a large, urban, public university in the Northeast. Using Tinto's (1993) model of student departure as a conceptual framework, the quantitative…

  11. Persistence of associated gram-negative bacteria in experimental actinomycotic lesions in mice.

    PubMed Central

    Jordan, H V; Kelly, D M

    1983-01-01

    Mixed actinomycotic infections were established in a susceptible weanling mouse model by using combinations of Actinomyces israelii and Eikenella corrodens or A. israelii and Actinobacillus actinomycetemcomitans. Acute lesions caused by either of the gram-negative organisms alone were resolved within a few weeks; however, these organisms persisted up to 3 months in chronic lesions in combination with A. israelii. PMID:6341251

  12. Resiliency, Self-Efficacy, and Persistence of College Seniors in Higher Education

    ERIC Educational Resources Information Center

    Garza, Kristopher K.; Bain, Steve F.; Kupczynski, Lori

    2014-01-01

    Institutions of higher learning have struggled to retain incoming freshmen, especially Hispanic students, who historically face greater challenges to succeed. The purpose of this mixed-methods study was to investigate the relationship between resiliency, self-efficacy, and persistence of college seniors with an emphasis on first- and…

  13. Continuation of point clouds via persistence diagrams

    NASA Astrophysics Data System (ADS)

    Gameiro, Marcio; Hiraoka, Yasuaki; Obayashi, Ippei

    2016-11-01

    In this paper, we present a mathematical and algorithmic framework for the continuation of point clouds by persistence diagrams. A key property used in the method is that the persistence map, which assigns a persistence diagram to a point cloud, is differentiable. This allows us to apply the Newton-Raphson continuation method in this setting. Given an original point cloud P, its persistence diagram D, and a target persistence diagram D‧, we gradually move from D to D‧, by successively computing intermediate point clouds until we finally find a point cloud P‧ having D‧ as its persistence diagram. Our method can be applied to a wide variety of situations in topological data analysis where it is necessary to solve an inverse problem, from persistence diagrams to point cloud data.

  14. Mixing and compaction temperatures for Superpave mixes

    NASA Astrophysics Data System (ADS)

    Yildirim, Yetkin

    According to Superpave mixture design, gyratory specimens are mixed and compacted at equiviscous binder temperatures corresponding to viscosities of 0.17 and 0.28 Pa.s. respectively. These were the values previously used in the Marshal mix design method to determine optimal mixing and compaction temperatures. In order to estimate the appropriate mixing and compaction temperatures for Superpave mixture design, a temperature-viscosity relationship for the binder needs to be developed (ASTM D 2493, Calculation of Mixing and Compaction Temperatures). The current approach is simple and provides reasonable temperatures for unmodified binders. However, some modified binders have exhibited unreasonably high temperatures for mixing and compaction using this technique. These high temperatures can result in construction problems, damage of asphalt, and production of fumes. Heating asphalt binder to very high temperatures during construction oxidizes the binder and separates the polymer from asphalt binder. It is known that polymer modified asphalt binders have many benefits to the roads, such as; increasing rutting resistance, enhancing low temperature cracking resistance, improving traction, better adhesion and cohesion, elevating tensile strength which are directly related to the service life of the pavement. Therefore, oxidation and separation of the polymer from the asphalt binder results in reduction of the service life. ASTM D 2493 was established for unmodified asphalt binders which are Newtonian fluids at high temperatures. For these materials, viscosity does not depend on shear rate. However, most of the modified asphalt binders exhibit a phenomenon known as pseudoplasticity, where viscosity does depend on shear rate. Thus, at the high shear rates occurring during mixing and compaction, it is not necessary to go to very high temperatures. This research was undertaken to determine the shear rate during compaction such that the effect of this parameter could be

  15. Oral Narrative Intervention for Children with Mixed Reading Disability

    ERIC Educational Resources Information Center

    Westerveld, Marleen F.; Gillon, Gail T.

    2008-01-01

    Ten children (aged between 7;11 and 9;2) with mixed reading disability participated in an oral narrative intervention programme that focused on enhancing children's story structure knowledge. The participants had all demonstrated persistent reading and oral narrative comprehension and production difficulties in a two-year longitudinal study prior…

  16. On enumeration of congeners of common persistent organic pollutants.

    PubMed

    Haranczyk, Maciej; Puzyn, Tomasz; Ng, Esmond G

    2010-08-01

    Congeners are molecules based on the same carbon skeleton but different by the number of substituents and/or a substitution pattern. Various Persistent Organic Pollutants (POPs) exist in the environment as families of halogen substituted congeners and/or their hydroxyl and methoxy substituted derivatives. Numbers of possible congeners resulting from substitution of a parent POP molecule with only one type of chemical group are generally available. At the same time, numbers of mixed-substituent congeners have not been counted and presented yet, although there is an increasing interest in such as is the increasing number of research articles presenting results on already identified Cl-/Br-mixed type congeners and/or their HO-/CH(3)O-mixed metabolites. We have enumerated and counted possible mixed-substituent congeners of common POPs. This article presents the obtained numbers for congener families of benzene, naphthalene, biphenyl, diphenyl ether, dibenzo-p-dioxin, dibenzofuran, anthracene, pyrene and others and obtained by substitution of up to five chemical group types.

  17. Topical triamcinolone for persistent phimosis.

    PubMed

    Letendre, Julien; Barrieras, Diego; Franc-Guimond, Julie; Abdo, Ala; Houle, Anne-Marie

    2009-10-01

    Between 2% and 5% of uncircumcised boys have persistent or pathological phimosis. Traditional treatment is usually circumcision. Recently medical treatment with topical corticosteroids has become more popular. We evaluated the efficacy of the topical steroid triamcinolone compared to foreskin retraction with an emollient cream and verified the long-term success rate of these treatments. We performed a double-blind, randomized, placebo controlled study to compare 2-month twice daily treatment with emollient cream (placebo group 1) vs 0.1% triamcinolone (experimental group 2). Boys between ages 3 and 12 years with persistent or pathological phimosis were included in analysis. Study EXCLUSION criteria were previous treatment with topical corticosteroid, untreated balanitis and any known medical condition with immune system impairment. Patients were seen 2, 4 and 12 months after treatment initiation. Success was defined as complete, easy foreskin retraction at 4 and 12 months. Statistical analysis was done using Fisher's exact test. We enrolled 63 patients, of whom 43 completed the study. Despite multiple attempts 20 patients had incomplete followup and were excluded from study. Placebo group 1 included 25 patients and triamcinolone group 2 included 21. In group 1 the success rate was significantly lower than in group 2 (9 patients or 39% vs 16 or 76%, p = 0.0086). At 2 months 5 and 16 nonresponders in groups 2 and 1, respectively, were treated in nonblinded fashion with topical triamcinolone. In this subgroup 1 of 3 group 2 patients and 6 of 13 in group 1 achieved complete, easy retraction. Two and 1 patients were lost to followup in groups 1 and 2, respectively. Circumcision was required in only 5 patients (11.6%), including 4 (17.4%) initially in group 1. No complications were noted in either group. Triamcinolone is a highly effective and safe short-term treatment for persistent physiological or pathological phimosis. However, at long-term followup recurrence is

  18. Dematerialization: Variety, caution, and persistence.

    PubMed

    Ausubel, Jesse H; Waggoner, Paul E

    2008-09-02

    Dematerialization, represented by declining consumption per GDP of energy or of goods, offers some hope for rising environmental quality with development. The declining proportion of income spent on staples as affluence grows, which income elasticity <1.0 measures, makes dematerialization widespread. Further, as learning improves efficiency of resource use, the intensity of environmental impact per production of staples often declines. We observe that combinations of low income elasticity for staples and of learning by producers cause a variety of dematerializations and declining intensities of impact, from energy use and carbon emission to food consumption and fertilizer use, globally and in countries ranging from the United States and France to China, India, Brazil, and Indonesia. Because dematerialization and intensity of impact are ratios of parameters that may be variously defined and are sometimes difficult to estimate, their fluctuations must be interpreted cautiously. Nevertheless, substantial declining intensity of impact, and especially, dematerialization persisted between 1980 and 2006.

  19. Persistent currents in ferromagnetic condensates

    NASA Astrophysics Data System (ADS)

    Lamacraft, Austen

    2017-06-01

    Persistent currents in Bose condensates with a scalar order parameter are stabilized by the topology of the order parameter manifold. In condensates with multicomponent order parameters it is topologically possible for supercurrents to "unwind" without leaving the manifold. We study the energetics of this process in the case of ferromagnetic condensates using a long wavelength energy functional that includes both the superfluid and spin stiffnesses. Exploiting analogies to an elastic rod and rigid body motion, we show that the current carrying state in a 1D ring geometry transitions between a spin helix in the energy minima and a solitonlike configuration at the maxima. The relevance to recent experiments in ultracold atoms is briefly discussed.

  20. Long-persistence blue phosphors

    NASA Technical Reports Server (NTRS)

    Yen, William M. (Inventor); Jia, Weiyi (Inventor); Lu, Lizhu (Inventor); Yuan, Huabiao (Inventor)

    2000-01-01

    This invention relates to phosphors including long-persistence blue phosphors. Phosphors of the invention are represented by the general formula: MO . mAl.sub.2 O.sub.3 :Eu.sup.2+,R.sup.3+ wherein m is a number ranging from about 1.6 to about 2.2, M is Sr or a combination of Sr with Ca and Ba or both, R.sup.3+ is a trivalent metal ion or trivalent Bi or a mixture of these trivalent ions, Eu.sup.2+ is present at a level up to about 5 mol % of M, and R.sup.3+ is present at a level up to about 5 mol % of M. Phosphors of this invention include powders, ceramics, single crystals and single crystal fibers. A method of manufacturing improved phosphors and a method of manufacturing single crystal phosphors are also provided.

  1. Persistent Pneumonia in an Infant

    PubMed Central

    Padilla, Kristen; Logan, Latania; Codispoti, Christopher; Jones, Carolyn

    2015-01-01

    A 4-month-old boy with past medical history of eczema presented with fever and cough; a chest radiograph showed lung consolidation, and he was initially treated with amoxicillin for presumed community-acquired pneumonia. After several days, his fever persisted. He was also profoundly anemic. Antibiotic coverage was broadened because of the concern for resistant organisms; he began to improve and was discharged from the hospital. However, at 5 months of age, his fever returned, and he continued to demonstrate lung consolidation on chest radiograph. Additionally, he had lost weight and continued to be anemic. Splenic cysts were noted on abdominal ultrasound. He was diagnosed with an unusual etiology for his pneumonia and improved with the appropriate therapy. An underlying immunodeficiency was suspected, but initial testing was nondiagnostic. At 12 months of age, he presented with another infection, and the final diagnosis was made. PMID:26122810

  2. Persistent Pneumonia in an Infant.

    PubMed

    Padilla, Kristen; Logan, Latania; Codispoti, Christopher; Jones, Carolyn; Van Opstal, Elizabeth

    2015-07-01

    A 4-month-old boy with past medical history of eczema presented with fever and cough; a chest radiograph showed lung consolidation, and he was initially treated with amoxicillin for presumed community-acquired pneumonia. After several days, his fever persisted. He was also profoundly anemic. Antibiotic coverage was broadened because of the concern for resistant organisms; he began to improve and was discharged from the hospital. However, at 5 months of age, his fever returned, and he continued to demonstrate lung consolidation on chest radiograph. Additionally, he had lost weight and continued to be anemic. Splenic cysts were noted on abdominal ultrasound. He was diagnosed with an unusual etiology for his pneumonia and improved with the appropriate therapy. An underlying immunodeficiency was suspected, but initial testing was nondiagnostic. At 12 months of age, he presented with another infection, and the final diagnosis was made.

  3. Dematerialization: Variety, caution, and persistence

    PubMed Central

    Ausubel, Jesse H.; Waggoner, Paul E.

    2008-01-01

    Dematerialization, represented by declining consumption per GDP of energy or of goods, offers some hope for rising environmental quality with development. The declining proportion of income spent on staples as affluence grows, which income elasticity <1.0 measures, makes dematerialization widespread. Further, as learning improves efficiency of resource use, the intensity of environmental impact per production of staples often declines. We observe that combinations of low income elasticity for staples and of learning by producers cause a variety of dematerializations and declining intensities of impact, from energy use and carbon emission to food consumption and fertilizer use, globally and in countries ranging from the United States and France to China, India, Brazil, and Indonesia. Because dematerialization and intensity of impact are ratios of parameters that may be variously defined and are sometimes difficult to estimate, their fluctuations must be interpreted cautiously. Nevertheless, substantial declining intensity of impact, and especially, dematerialization persisted between 1980 and 2006. PMID:18728190

  4. Persistent nicorandil induced oral ulceration

    PubMed Central

    Healy, C M; Smyth, Y; Flint, S R

    2004-01-01

    Four patients with nicorandil induced ulceration are described, and the literature on the subject is reviewed. Nicorandil induced ulcers are very painful and distressing for patients. Clinically they appear as large, deep, persistent ulcers that have punched out edges. They are poorly responsive to topical steroids and usually require alteration of nicorandil treatment. The ulceration tends to occur at high doses of nicorandil and all four cases reported here were on doses of 40 mg per day or greater. In these situations reduction of nicorandil dose may be sufficient to promote ulcer healing and prevent further recurrence. However, nicorandil induced ulcers have been reported at doses as low as 10 mg daily and complete cessation of nicorandil may be required. PMID:15201264

  5. Psychoacoustic classification of persistent tinnitus.

    PubMed

    Suzuki, Flavia Alencar de Barros; Suzuki, Fabio Akira; Onishi, Ektor Tsuneo; Penido, Norma Oliveira

    2017-08-01

    Tinnitus is a difficult to treat symptom, with different responses in patients. It is classified in different ways, according to its origin and associated diseases. to propose a single and measurable classification of persistent tinnitus, through its perception as sounds of nature or of daily life and its comparison with pure tone or noise, of high or low pitch, presented to the patient by audiometer sound. A total of 110 adult patients, of both genders, treated at the Tinnitus Outpatient Clinic, were enrolled according to the inclusion and exclusion criteria. Otorhinolaryngologic and Audiological, Pitch Matching and Loudness, Visual Analog Scale, Tinnitus Handicap Inventory and Minimum Masking Level assessments were performed. In these 110 patients, 181 tinnitus complaints were identified accordingly to type and ear, with 93 (51%) Pure Tone, and 88 (49%) Noise type; 19 at low and 162 at high frequency; with a mean in the Pure Tone of 5.47 in the Visual Analog Scale and 12.31 decibel in the Loudness and a mean in the Noise of 6.66 and 10.51 decibel. For Tinnitus Handicap Inventory and Minimum Masking Level, the 110 patients were separated into three groups with tinnitus, Pure Tone, Noise and multiple. Tinnitus Handicap Inventory higher in the group with multiple tinnitus, of 61.38. Masking noises such as White Noise and Narrow Band were used for the Minimum Masking Level at the frequencies of 500 and 6000Hz. There was a similarity between the Pure Tone and Multiple groups. In the Noise group, different responses were found when Narrow Band was used at low frequency. classifying persistent tinnitus as pure tone or noise, present in high or low frequency and establishing its different characteristics allow us to know its peculiarities and the effects of this symptom in patients' lives. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  6. Appearance of the persistently low tropopause temperature and ozone over the Bay of Bengal region

    NASA Astrophysics Data System (ADS)

    Jain, Shipra; Jain, A. R.; Mandal, T. K.

    2017-09-01

    This paper reports the observation of persistently low tropopause temperatures (100 hPa temperatures, T 100) and ozone at 100 hPa throughout the year as compared to the corresponding zonal mean values over the Bay of Bengal (BOB) region. The long term mean T 100 (i.e., from January 2006-December 2009) over the BOB is 2.2 K lower than the zonal mean values over this region. The multiple linear regression analysis has been carried out to study the role of convection and ozone in giving rise to the persistently low T 100 over the BOB. Results show that the low ozone mixing ratios contributes 1.2 K and convection contributes 0.35 K to the persistently low T 100. The contribution of convection to the persistent low T 100 is mainly during the boreal monsoon season.

  7. Human mobility networks and persistence of rapidly mutating pathogens

    PubMed Central

    Aleta, Alberto; Hisi, Andreia N. S.; Colizza, Vittoria; Moreno, Yamir

    2017-01-01

    Rapidly mutating pathogens may be able to persist in the population and reach an endemic equilibrium by escaping hosts’ acquired immunity. For such diseases, multiple biological, environmental and population-level mechanisms determine the dynamics of the outbreak, including pathogen's epidemiological traits (e.g. transmissibility, infectious period and duration of immunity), seasonality, interaction with other circulating strains and hosts’ mixing and spatial fragmentation. Here, we study a susceptible-infected-recovered-susceptible model on a metapopulation where individuals are distributed in sub-populations connected via a network of mobility flows. Through extensive numerical simulations, we explore the phase space of pathogen's persistence and map the dynamical regimes of the pathogen following emergence. Our results show that spatial fragmentation and mobility play a key role in the persistence of the disease whose maximum is reached at intermediate mobility values. We describe the occurrence of different phenomena including local extinction and emergence of epidemic waves, and assess the conditions for large-scale spreading. Findings are highlighted in reference to previous studies and to real scenarios. Our work uncovers the crucial role of hosts’ mobility on the ecological dynamics of rapidly mutating pathogens, opening the path for further studies on disease ecology in the presence of a complex and heterogeneous environment. PMID:28405379

  8. Science Identity's Influence on Community College Students' Engagement, Persistence, and Performance in Biology

    NASA Astrophysics Data System (ADS)

    Riccitelli, Melinda

    In the United States (U.S.), student engagement, persistence, and academic performance levels in college science, technology, engineering, and mathematics (STEM) programs have been unsatisfactory over the last decade. Low student engagement, persistence, and academic performance in STEM disciplines have been identified as major obstacles to U.S. economic goals and U.S. science education objectives. The central and salient science identity a college student claims can influence his engagement, persistence, and academic achievement in college science. While science identity studies have been conducted on four-year college populations there is a gap in the literature concerning community college students' science identity and science performance. The purpose of this quantitative correlational study was to examine the relationship between community college students claimed science identities and engagement, persistence, and academic performance. A census sample of 264 community college students enrolled in biology during the summer of 2015 was used to study this relationship. Science identity and engagement levels were calculated using the Science Identity Centrality Scale and the Biology Motivation Questionnaire II, respectively. Persistence and final grade data were collected from institutional and instructor records. Engagement significantly correlated to, r =.534, p = .01, and varied by science identity, p < .001. Percent final grade also varied by science identity (p < .005), but this relationship was weaker (r = .208, p = .01). Results for science identity and engagement and final grade were consistent with the identity literature. Persistence did not vary by science identity in this student sample (chi2 =2.815, p = .421). This result was inconsistent with the literature on science identity and persistence. Quantitative results from this study present a mixed picture of science identity status at the community college level. It is suggested, based on the findings

  9. Persistent pulmonary hypertension of the neonate (persistent fetal circulation syndrome).

    PubMed

    Drummond, W H

    1983-01-01

    This 15-year-old disease has been clearly described anatomically. Some understanding of possible in utero predisposing conditions has emerged from clinical and animal studies. However, we have very little understanding of the cellular processes that trigger and/or prolong the abnormal medial smooth muscle hypertrophy underlying the condition. Empiric observation has resulted in the development of hyperventilation as a fairly successful treatment modality, although the underlying mechanism of this salubrious effect is unknown. Drugs, a major focus of clinical and laboratory investigations, sometimes are marginally successful (and sometimes are utter failures). Translated into the neonatal intensive care unit, the disease is more frequently accurately diagnosed than in the past, but it remains frustratingly difficult to manage, and thus far is impossible to prevent. The research foundations laid in the past decade provide impetus for accelerated search into the fundamental cellular and biochemical derangements that cause persistent pulmonary hypertension. It is to be hoped that the next decade will yield major advances in both mechanistic understanding and in treatment.

  10. High turnover drives prolonged persistence of influenza in managed pig herds

    PubMed Central

    Aguas, Ricardo; Riley, Steven; Loeffen, Willie L. A.; Wood, James L. N.; Grenfell, Bryan T.

    2016-01-01

    Pigs have long been hypothesized to play a central role in the emergence of novel human influenza A virus (IAV) strains, by serving as mixing vessels for mammalian and avian variants. However, the key issue of viral persistence in swine populations at different scales is ill understood. We address this gap using epidemiological models calibrated against seroprevalence data from Dutch finishing pigs to estimate the ‘critical herd size’ (CHS) for IAV persistence. We then examine the viral phylogenetic evidence for persistence by comparing human and swine IAV. Models suggest a CHS of approximately 3000 pigs above which influenza was likely to persist, i.e. orders of magnitude lower than persistence thresholds for IAV and other acute viruses in humans. At national and regional scales, we found much stronger empirical signatures of prolonged persistence of IAV in swine compared with human populations. These striking levels of persistence in small populations are driven by the high recruitment rate of susceptible piglets, and have significant implications for management of swine and for overall patterns of genetic diversity of IAV. PMID:27358277

  11. High turnover drives prolonged persistence of influenza in managed pig herds.

    PubMed

    Pitzer, Virginia E; Aguas, Ricardo; Riley, Steven; Loeffen, Willie L A; Wood, James L N; Grenfell, Bryan T

    2016-06-01

    Pigs have long been hypothesized to play a central role in the emergence of novel human influenza A virus (IAV) strains, by serving as mixing vessels for mammalian and avian variants. However, the key issue of viral persistence in swine populations at different scales is ill understood. We address this gap using epidemiological models calibrated against seroprevalence data from Dutch finishing pigs to estimate the 'critical herd size' (CHS) for IAV persistence. We then examine the viral phylogenetic evidence for persistence by comparing human and swine IAV. Models suggest a CHS of approximately 3000 pigs above which influenza was likely to persist, i.e. orders of magnitude lower than persistence thresholds for IAV and other acute viruses in humans. At national and regional scales, we found much stronger empirical signatures of prolonged persistence of IAV in swine compared with human populations. These striking levels of persistence in small populations are driven by the high recruitment rate of susceptible piglets, and have significant implications for management of swine and for overall patterns of genetic diversity of IAV.

  12. Dualities in Persistent (Co)Homology

    SciTech Connect

    de Silva, Vin; Morozov, Dmitriy; Vejdemo-Johansson, Mikael

    2011-09-16

    We consider sequences of absolute and relative homology and cohomology groups that arise naturally for a filtered cell complex. We establishalgebraic relationships between their persistence modules, and show that they contain equivalent information. We explain how one can use the existingalgorithm for persistent homology to process any of the four modules, and relate it to a recently introduced persistent cohomology algorithm. Wepresent experimental evidence for the practical efficiency of the latter algorithm.

  13. A model for persistency of egg production.

    PubMed

    Grossman, M; Gossman, T N; Koops, W J

    2000-12-01

    The objectives of our study were to propose a new definition for persistency of egg production and to develop a mathematical model to describe the egg production curve, one that includes a new measure for persistency, based on the proposed definition, for use as a selection criterion to improve total egg production. Persistency of egg production is an important determining factor for total egg production. Hens with the same total production, however, can exhibit different egg production curves because of differences in persistency. We propose a new definition for persistency of egg production: the number of weeks during which a level of constant production is maintained. No egg production model exists that includes a measure of persistency in terms of duration of time or that allows this measure of persistency to be derived from model parameters. It was necessary, therefore, to develop a new model to describe an egg production curve for a flock: equation [see text] and for an individual: equation [see text] where y(t) = egg production at time t, t1 and t2 = times at transition, r = duration of transition, y(p) = level of constant production, b4 = rate of decline in production, and P = persistency of constant production. These parameters measure directly the important biological characteristics of an egg production curve. To illustrate the model, six data sets were used: two from flocks (one pullet flock and one hen flock) and four from two pairs of individuals. The proposed definition of persistency should be important for genetic selection because it might be desirable to select for increased persistency. The novel approach to the definition and measure of persistency presented here should provide a better understanding of the relationship between the new measure of persistency and other characteristics of egg production.

  14. Persistent homology analysis of craze formation

    NASA Astrophysics Data System (ADS)

    Ichinomiya, Takashi; Obayashi, Ippei; Hiraoka, Yasuaki

    2017-01-01

    We apply a persistent homology analysis to investigate the behavior of nanovoids during the crazing process of glassy polymers. We carry out a coarse-grained molecular dynamics simulation of the uniaxial deformation of an amorphous polymer and analyze the results with persistent homology. Persistent homology reveals the void coalescence during craze formation, and the results suggest that the yielding process is regarded as the percolation of nanovoids created by deformation.

  15. Mixed oxide solid solutions

    DOEpatents

    Magno, Scott; Wang, Ruiping; Derouane, Eric

    2003-01-01

    The present invention is a mixed oxide solid solution containing a tetravalent and a pentavalent cation that can be used as a support for a metal combustion catalyst. The invention is furthermore a combustion catalyst containing the mixed oxide solid solution and a method of making the mixed oxide solid solution. The tetravalent cation is zirconium(+4), hafnium(+4) or thorium(+4). In one embodiment, the pentavalent cation is tantalum(+5), niobium(+5) or bismuth(+5). Mixed oxide solid solutions of the present invention exhibit enhanced thermal stability, maintaining relatively high surface areas at high temperatures in the presence of water vapor.

  16. Cement mixing with vibrator

    SciTech Connect

    Allen, T.E.

    1991-07-09

    This patent describes a method of cementing a casing string in a bore hole of a well. It comprises introducing water and dry cement material into a mixing vessel; mixing the water and dry cement material in the mixing vessel to form a cement slurry, the slurry including lumps of the dry cement material, the mixing including steps of: agitating the slurry; and while agitating the slurry, transmitting vibrational energy into the slurry and thereby aiding disintegration and subsequent wetting of the lumps of the dry cement material in the slurry; and pumping the slurry into an annulus between the casing string and the bore hole.

  17. Persistence Measures for 2d Soap Froth

    NASA Astrophysics Data System (ADS)

    Feng, Y.; Ruskin, H. J.; Zhu, B.

    Soap froths as typical disordered cellular structures, exhibiting spatial and temporal evolution, have been studied through their distributions and topological properties. Recently, persistence measures, which permit representation of the froth as a two-phase system, have been introduced to study froth dynamics at different length scales. Several aspects of the dynamics may be considered and cluster persistence has been observed through froth experiment. Using a direct simulation method, we have investigated persistent properties in 2D froth both by monitoring the persistence of survivor cells, a topologically independent measure, and in terms of cluster persistence. It appears that the area fraction behavior for both survivor and cluster persistence is similar for Voronoi froth and uniform froth (with defects). Survivor and cluster persistent fractions are also similar for a uniform froth, particularly when geometries are constrained, but differences observed for the Voronoi case appear to be attributable to the strong topological dependency inherent in cluster persistence. Survivor persistence, on the other hand, depends on the number rather than size and position of remaining bubbles and does not exhibit the characteristic decay to zero.

  18. Mixed waste minimization/mixed waste avoidance

    SciTech Connect

    Todisco, L.R.

    1994-12-31

    This presentation describes methods for the minimization and volume reduction of low-level radioactive and mixed wastes. Many methods are presented including: source reduction, better waste monitoring activities, waste segregation, recycling, administrative controls, and optimization of waste-generating processes.

  19. Persistant photoconductivity of strontium titanate

    NASA Astrophysics Data System (ADS)

    Poole, Violet Mary

    Strontium titanate (SrTiO3) is a transparent conducting oxide with a range of interesting properties, including a large, temperature-dependent dielectric constant and superconductivity at low temperatures. It has a wide indirect band gap of 3.2 eV at room temperature. Annealing in a reducing atmosphere with additional strontium oxide (SrO) powder at 1200°C results in the creation of native defects. These annealed samples show persistent photoconductivity (PPC) at room temperature, when exposed to light of energy 2.9 eV or greater. The three or more order of magnitude change in resistance persists long after the light is turned off. This effect is attributed to an electron being excited from an acceptor defect, with a large barrier for recapture, to the conduction band. This work investigates many of the changes that occur and factors that affect PPC. The right amount of SrO powder is crucial to the formation of PPC. The presence of some oxygen vacancies is also necessary for PPC; however, too many will mute the dramatic change in resistivity. Peaks at 430 nm and 520 nm appear in the visible region of the spectrum. The peak at 430 nm is due to iron, while the peak at 520 nm has not been identified. The infrared region of the spectrum also shows changes. First, the intensity of the transmitted signal drops significantly after light exposure, due to free carrier absorption. Additionally, a hydrogen line at 3500 cm-1 and satellites are often observed in as-received samples. The satellites disappear during annealing and return during PPC. The hydrogen lines have the same thermal kinetics as the 520 nm peak. Hydrogen lines at 3355 and 3384 cm-1, if present, will prevent PPC. An exposed chip can be erased (i.e. returned to its pre-light exposed state) by using a heat treatment. Erasing and polishing an annealed chip prior to light exposure can result in weakly p-type behavior with high mobility holes ( > 100 cm2/Vs). This is an order of magnitude higher than those

  20. Unrelated toxin–antitoxin systems cooperate to induce persistence

    PubMed Central

    Fasani, Rick A.; Savageau, Michael A.

    2015-01-01

    of growing and non-growing cells, typical of persisters, that exist under normal conditions, rather than only as an induced response. The frequency of persisters in the population can be tuned for a particular environmental niche by mixing and matching unrelated systems via mutation, horizontal gene transfer and selection. PMID:26063817

  1. Admission mixing duct assembly

    NASA Technical Reports Server (NTRS)

    Orlando, Robert J. (Inventor); Dunbar, Lawrence W. (Inventor)

    1995-01-01

    A variable cycle jet engine is provided with a mixing duct assembly which mixes core engine exhaust gas with bypass air when the engine is operating in a turbofan mode and which blocks flow from the core engine and isolates the core engine from the bypass flow when the engine is operating as a ramjet.

  2. Dilution Zone Mixing

    NASA Technical Reports Server (NTRS)

    Holdeman, J. D.

    1983-01-01

    Studies to characterize dilution zone mixing; experiments on the effects of free-stream turbulence on a jet in crossflow; and the development of an interactive computer code for the analysis of the mixing of jets with a confined crossflow are reviewed.

  3. A PILOT STUDY OF CHILDREN'S TOTAL EXPOSURE TO PERSISTENT PESTICIDES AND OTHER PERSISTENT ORGANIC POLLUTANTS (CTEPP)

    EPA Science Inventory

    The Pilot Study of Children's Total Exposure to Persistent Pesticides and Other Persistent Organic Pollutants (CTEPP) investigated the aggregate exposures of 257 preschool children and their primary adult caregivers to pollutants commonly detected in their everyday environments. ...

  4. A PILOT STUDY OF CHILDREN'S TOTAL EXPOSURE TO PERSISTENT PESTICIDES AND OTHER PERSISTENT ORGANIC POLLUTANTS (CTEPP)

    EPA Science Inventory

    The Pilot Study of Children's Total Exposure to Persistent Pesticides and Other Persistent Organic Pollutants (CTEPP) investigated the aggregate exposures of 257 preschool children and their primary adult caregivers to pollutants commonly detected in their everyday environments. ...

  5. An Evaluation of Persistence of Treatment Effects During Long-Term Treatment of Destructive Behavior

    PubMed Central

    Wacker, David P; Harding, Jay W; Berg, Wendy K; Lee, John F; Schieltz, Kelly M; Padilla, Yaniz C; Nevin, John A; Shahan, Timothy A

    2011-01-01

    Eight young children who displayed destructive behavior maintained, at least in part, by negative reinforcement received long-term functional communication training (FCT). During FCT, the children completed a portion of a task and then touched a communication card attached to a microswitch to obtain brief breaks. Prior to and intermittently throughout FCT, extinction probes were conducted within a withdrawal design in which task completion, manding, and destructive behavior were placed on extinction to evaluate the relative persistence of appropriate and destructive behavior over the course of treatment. FCT continued until appropriate behavior persisted and destructive behavior failed to recur at baseline levels during extinction probes. The completion of FCT was followed by four challenges to the persistence of treatment effects conducted within mixed- or multiple-schedule designs: (a) extended extinction sessions (from 5 to 15 min), (b) introduction of a novel task, (c) removal of the microswitch and communication card, and (d) a mixed schedule of reinforcement in which both appropriate and destructive behavior produced reinforcement. The results showed that although FCT often resulted in quick reductions in destructive behavior and increases in appropriate behavior, destructive behavior often recurred during the extinction probes conducted during the initial treatment. When the effects of treatment persisted during the extinction probes, the remaining challenges to treatment effects resulted in only mild to moderate disruptions in behavior. These results are consistent with the quantitative predictions of behavioral momentum theory and may provide an alternative definition of maintenance as constituting behavioral persistence. PMID:21909168

  6. An evaluation of persistence of treatment effects during long-term treatment of destructive behavior.

    PubMed

    Wacker, David P; Harding, Jay W; Berg, Wendy K; Lee, John F; Schieltz, Kelly M; Padilla, Yaniz C; Nevin, John A; Shahan, Timothy A

    2011-09-01

    Eight young children who displayed destructive behavior maintained, at least in part, by negative reinforcement received long-term functional communication training (FCT). During FCT, the children completed a portion of a task and then touched a communication card attached to a microswitch to obtain brief breaks. Prior to and intermittently throughout FCT, extinction probes were conducted within a withdrawal design in which task completion, manding, and destructive behavior were placed on extinction to evaluate the relative persistence of appropriate and destructive behavior over the course of treatment. FCT continued until appropriate behavior persisted and destructive behavior failed to recur at baseline levels during extinction probes. The completion of FCT was followed by four challenges to the persistence of treatment effects conducted within mixed- or multiple-schedule designs: (a) extended extinction sessions (from 5 to 15 min), (b) introduction of a novel task, (c) removal of the microswitch and communication card, and (d) a mixed schedule of reinforcement in which both appropriate and destructive behavior produced reinforcement. The results showed that although FCT often resulted in quick reductions in destructive behavior and increases in appropriate behavior, destructive behavior often recurred during the extinction probes conducted during the initial treatment. When the effects of treatment persisted during the extinction probes, the remaining challenges to treatment effects resulted in only mild to moderate disruptions in behavior. These results are consistent with the quantitative predictions of behavioral momentum theory and may provide an alternative definition of maintenance as constituting behavioral persistence.

  7. Microfluidic Mixing: A Review

    PubMed Central

    Lee, Chia-Yen; Chang, Chin-Lung; Wang, Yao-Nan; Fu, Lung-Ming

    2011-01-01

    The aim of microfluidic mixing is to achieve a thorough and rapid mixing of multiple samples in microscale devices. In such devices, sample mixing is essentially achieved by enhancing the diffusion effect between the different species flows. Broadly speaking, microfluidic mixing schemes can be categorized as either “active”, where an external energy force is applied to perturb the sample species, or “passive”, where the contact area and contact time of the species samples are increased through specially-designed microchannel configurations. Many mixers have been proposed to facilitate this task over the past 10 years. Accordingly, this paper commences by providing a high level overview of the field of microfluidic mixing devices before describing some of the more significant proposals for active and passive mixers. PMID:21686184

  8. Theory for Neutrino Mixing

    NASA Astrophysics Data System (ADS)

    He, Xiao-Gang

    2016-07-01

    Since the discovery of neutrino oscillations, for which Takaaki Kajita and Arthur B. McDonald were awarded the 2015 Nobel prize in physics, tremendous progresses have been made in measuring the mixing angles which determine the oscillation pattern. A lot of theoretical efforts have been made to understand how neutrinos mix with each other. Present data show that in the standard parameterization of the mixing matrix, θ23 is close to π/4 and the CP violating phase is close to - π/2. In this talk I report results obtained in arXiv:1505.01932 (Phys. Lett. B750(2015)620) and arXive:1404.01560 (Chin. J. Phys.53(2015)100101) and discuss some implications for theoretical model buildings for such mixing pattern. Specific examples for neutrino mixing based on A4 family symmetry are given.

  9. High-mix insulins

    PubMed Central

    Kalra, Sanjay; Farooqi, Mohammad Hamed; El-Houni, Ali E.

    2015-01-01

    Premix insulins are commonly used insulin preparations, which are available in varying ratios of different molecules. These drugs contain one short- or rapid-acting, and one intermediate- or long-acting insulin. High-mix insulins are mixtures of insulins that contain 50% or more than 50% of short-acting insulin. This review describes the clinical pharmacology of high-mix insulins, including data from randomized controlled trials. It suggests various ways, in which high-mix insulin can be used, including once daily, twice daily, thrice daily, hetero-mix, and reverse regimes. The authors provide a rational framework to help diabetes care professionals, identify indications for pragmatic high-mix use. PMID:26425485

  10. MHD turbulent mixing layers

    SciTech Connect

    Esquivel, A.; Lazarian, A.; Benjamin, R.A.; Cho, J.; Leitner, S.N.

    2005-09-28

    Turbulent mixing layers have been proposed to explain observations of line ratios of highly ionized elements in the interstellar medium. We present preliminary results of numerical simulations of turbulent mixing layers in a magnetized medium. We developed a MHD code with radiative cooling. The magnetic field is expected to be a controlling factor by suppressing instabilities that lead to the turbulent mixing. Our results suggest that the difference in turbulent mixing in the unmagnetized case as compared to the case of a weak magnetic field, {beta} = Pgas/Pmag {approx} 10, is insignificant. With a more thorough exploration of parameter space, this work will provide more reliable diagnostics of turbulent mixing layers than those available today.

  11. Mixing dynamics of cutting and shuffling for granular materials

    NASA Astrophysics Data System (ADS)

    Lueptow, Richard M.; Zaman, Zafir; Yu, Mengqi; Park, Paul P.; Ottino, Julio M.; Umbanhowar, Paul B.

    2016-11-01

    Chaotic dynamics has been shown to play a major role in fluid mixing, but the study of its relevance to granular flows has only recently begun. We utilize a simple 3D geometry, a half-filled spherical tumbler rotated alternately by <= π /2 about two perpendicular horizontal axes, to develop a dynamical systems framework for granular mixing and non-mixing. In these systems, mixing can only occur during flow (from stretching due to shear and from collisional diffusion in the flowing layer) or by material separation intrinsic to the rotation protocol resulting from cutting and shuffling. In X-ray subsurface visualization experiments, surprisingly persistent (O(100) iterations) non-mixing elliptical regions and larger non-mixing barriers occur as predicted by both a continuum model and an idealized theoretical model (with an infinitely thin flowing layer) based on the mathematics of piece-wise isometries. In these models, the stretching in the flowing layer vanishes as the flowing layer thickness decreases to reveal the underlying skeleton of the mixing. This dynamical systems perspective provides insight into mixing and non-mixing phenomena unique to granular materials. Funded by NSF Grant CMMI-1435065.

  12. Persistence of Undergraduate Women in STEM Fields

    ERIC Educational Resources Information Center

    Pedone, Maggie Helene

    2016-01-01

    The underrepresentation of women in science, technology, engineering, and mathematics (STEM) is a complex problem that continues to persist at the postsecondary level, particularly in computer science and engineering fields. This dissertation explored the pre-college and college level factors that influenced undergraduate women's persistence in…

  13. Long Persistent Light Emitting Diode Indicators

    ERIC Educational Resources Information Center

    Jia, Dongdong; Ma, Yiwei; Hunter, D. N.

    2007-01-01

    An undergraduate laboratory was designed for undergraduate students to make long persistent light emitting diode (LED) indicators using phosphors. Blue LEDs, which emit at 465 nm, were characterized and used as an excitation source. Long persistent phosphors, SrAl[subscript 2]O[subscript 4]:Eu[superscript 2+],Dy[superscript 3+] (green) and…

  14. Personality Characteristics in Relation to College Persistence

    ERIC Educational Resources Information Center

    Johnson, Duane E.

    1970-01-01

    Scales of the Minnesota Counseling Inventory (MCI) were used to compare persisters with nonpersisters. All four comparisons involving the Conformity scale and two of four comparisons involving the Family Relationships scale demonstrated significant differences. Persisters scored lower than nonpersisters on all comparisons involving the Conformity…

  15. Correlated neural variability in persistent state networks.

    PubMed

    Polk, Amber; Litwin-Kumar, Ashok; Doiron, Brent

    2012-04-17

    Neural activity that persists long after stimulus presentation is a biological correlate of short-term memory. Variability in spiking activity causes persistent states to drift over time, ultimately degrading memory. Models of short-term memory often assume that the input fluctuations to neural populations are independent across cells, a feature that attenuates population-level variability and stabilizes persistent activity. However, this assumption is at odds with experimental recordings from pairs of cortical neurons showing that both the input currents and output spike trains are correlated. It remains unclear how correlated variability affects the stability of persistent activity and the performance of cognitive tasks that it supports. We consider the stochastic long-timescale attractor dynamics of pairs of mutually inhibitory populations of spiking neurons. In these networks, persistent activity was less variable when correlated variability was globally distributed across both populations compared with the case when correlations were locally distributed only within each population. Using a reduced firing rate model with a continuum of persistent states, we show that, when input fluctuations are correlated across both populations, they drive firing rate fluctuations orthogonal to the persistent state attractor, thereby causing minimal stochastic drift. Using these insights, we establish that distributing correlated fluctuations globally as opposed to locally improves network's performance on a two-interval, delayed response discrimination task. Our work shows that the correlation structure of input fluctuations to a network is an important factor when determining long-timescale, persistent population spiking activity.

  16. Supplemental Instruction: Supporting Persistence in Barrier Courses

    ERIC Educational Resources Information Center

    Bronstein, Susan B.

    2008-01-01

    Courses that interfere with undergraduate students' persistence are barriers that appear all along the undergraduate continuum. Supplemental Instruction (SI) may contribute to students' achievement in a barrier course and, therefore, to their persistence in their academic program. The purpose of this single-case descriptive study was to explore…

  17. The meaning of persistent infections in nature

    PubMed Central

    Mims, Cedric A.

    1975-01-01

    Viruses that cause persistent infections maintain themselves more effectively in nature than those causing acute and limited infections. There is a tendency for persistent viruses to evolve towards a state of minimal pathogenicity in the host. Vertical transmission, with integration of viral into host genome, represents the state of perfect parasitism. PMID:1085228

  18. Graduate Student Persistence: Evidence from Three Decades

    ERIC Educational Resources Information Center

    Gururaj, Suchitra; Heilig, Julian Vasquez; Somers, Patricia

    2010-01-01

    This article conducts a meta-analysis of results of studies by Andrieu (1991), DeAngelis (1998), and Liseo (2005) to assess changes over time in the effects of financial aid and other factors on graduate student persistence. A descriptive review of the studies finds that combination aid packages encouraged persistence in 1987 (Andrieu, 1991),…

  19. Long Persistent Light Emitting Diode Indicators

    ERIC Educational Resources Information Center

    Jia, Dongdong; Ma, Yiwei; Hunter, D. N.

    2007-01-01

    An undergraduate laboratory was designed for undergraduate students to make long persistent light emitting diode (LED) indicators using phosphors. Blue LEDs, which emit at 465 nm, were characterized and used as an excitation source. Long persistent phosphors, SrAl[subscript 2]O[subscript 4]:Eu[superscript 2+],Dy[superscript 3+] (green) and…

  20. Persistence of Undergraduate Women in STEM Fields

    ERIC Educational Resources Information Center

    Pedone, Maggie Helene

    2016-01-01

    The underrepresentation of women in science, technology, engineering, and mathematics (STEM) is a complex problem that continues to persist at the postsecondary level, particularly in computer science and engineering fields. This dissertation explored the pre-college and college level factors that influenced undergraduate women's persistence in…

  1. Counseling on Campus: Client Persistence and Progress

    ERIC Educational Resources Information Center

    Lucas, Margaretha S.

    2012-01-01

    Two related studies addressed college students' persistence and progress in psychotherapy. In Study 1, using emotional health variables assessed at intake, students who persisted in counseling and demonstrated clinical improvement were compared with those who either did not return for their first session or who did return but stopped before…

  2. ADVANCED MIXING MODELS

    SciTech Connect

    Lee, S; Richard Dimenna, R; David Tamburello, D

    2008-11-13

    The process of recovering the waste in storage tanks at the Savannah River Site (SRS) typically requires mixing the contents of the tank with one to four dual-nozzle jet mixers located within the tank. The typical criteria to establish a mixed condition in a tank are based on the number of pumps in operation and the time duration of operation. To ensure that a mixed condition is achieved, operating times are set conservatively long. This approach results in high operational costs because of the long mixing times and high maintenance and repair costs for the same reason. A significant reduction in both of these costs might be realized by reducing the required mixing time based on calculating a reliable indicator of mixing with a suitably validated computer code. The work described in this report establishes the basis for further development of the theory leading to the identified mixing indicators, the benchmark analyses demonstrating their consistency with widely accepted correlations, and the application of those indicators to SRS waste tanks to provide a better, physically based estimate of the required mixing time. Waste storage tanks at SRS contain settled sludge which varies in height from zero to 10 ft. The sludge has been characterized and modeled as micron-sized solids, typically 1 to 5 microns, at weight fractions as high as 20 to 30 wt%, specific gravities to 1.4, and viscosities up to 64 cp during motion. The sludge is suspended and mixed through the use of submersible slurry jet pumps. To suspend settled sludge, water is added to the tank as a slurry medium and stirred with the jet pump. Although there is considerable technical literature on mixing and solid suspension in agitated tanks, very little literature has been published on jet mixing in a large-scale tank. If shorter mixing times can be shown to support Defense Waste Processing Facility (DWPF) or other feed requirements, longer pump lifetimes can be achieved with associated operational cost and

  3. STEM Field Persistence: The Impact of Engagement on Postsecondary STEM Persistence for Underrepresented Minority Students

    ERIC Educational Resources Information Center

    Flynn, Daniel T.

    2016-01-01

    Persistence studies in science, technology, engineering, and math (STEM) fields indicate that the pipeline to degree attainment is "leaky" and underrepresented minorities are not persisting in the STEM fields. Those students who do not persist in the STEM fields either migrate to other fields of study or drop out of higher education…

  4. Type I Interferon Receptor Deficiency in Dendritic Cells Facilitates Systemic Murine Norovirus Persistence Despite Enhanced Adaptive Immunity.

    PubMed

    Nice, Timothy J; Osborne, Lisa C; Tomov, Vesselin T; Artis, David; Wherry, E John; Virgin, Herbert W

    2016-06-01

    In order for a virus to persist, there must be a balance between viral replication and immune clearance. It is commonly believed that adaptive immunity drives clearance of viral infections and, thus, dysfunction or viral evasion of adaptive immunity is required for a virus to persist. Type I interferons (IFNs) play pleiotropic roles in the antiviral response, including through innate control of viral replication. Murine norovirus (MNoV) replicates in dendritic cells (DCs) and type I IFN signaling in DCs is important for early control of MNoV replication. We show here that the non-persistent MNoV strain CW3 persists systemically when CD11c positive DCs are unable to respond to type I IFN. Persistence in this setting is associated with increased early viral titers, maintenance of DC numbers, increased expression of DC activation markers and an increase in CD8 T cell and antibody responses. Furthermore, CD8 T cell function is maintained during the persistent phase of infection and adaptive immune cells from persistently infected mice are functional when transferred to Rag1-/- recipients. Finally, increased early replication and persistence are also observed in mixed bone marrow chimeras where only half of the CD11c positive DCs are unable to respond to type I IFN. These findings demonstrate that increased early viral replication due to a cell-intrinsic innate immune deficiency is sufficient for persistence and a functional adaptive immune response is not sufficient for viral clearance.

  5. Reprogramming of Yersinia from Virulent to Persistent Mode Revealed by Complex In Vivo RNA-seq Analysis

    PubMed Central

    Avican, Kemal; Fahlgren, Anna; Huss, Mikael; Heroven, Ann Kathrin; Beckstette, Michael; Dersch, Petra; Fällman, Maria

    2015-01-01

    We recently found that Yersinia pseudotuberculosis can be used as a model of persistent bacterial infections. We performed in vivo RNA-seq of bacteria in small cecal tissue biopsies at early and persistent stages of infection to determine strategies associated with persistence. Comprehensive analysis of mixed RNA populations from infected tissues revealed that Y. pseudotuberculosis undergoes transcriptional reprogramming with drastic down-regulation of T3SS virulence genes during persistence when the pathogen resides within the cecum. At the persistent stage, the expression pattern in many respects resembles the pattern seen in vitro at 26oC, with for example, up-regulation of flagellar genes and invA. These findings are expected to have impact on future rationales to identify suitable bacterial targets for new antibiotics. Other genes that are up-regulated during persistence are genes involved in anaerobiosis, chemotaxis, and protection against oxidative and acidic stress, which indicates the influence of different environmental cues. We found that the Crp/CsrA/RovA regulatory cascades influence the pattern of bacterial gene expression during persistence. Furthermore, arcA, fnr, frdA, and wrbA play critical roles in persistence. Our findings suggest a model for the life cycle of this enteropathogen with reprogramming from a virulent to an adapted phenotype capable of persisting and spreading by fecal shedding. PMID:25590628

  6. The long persistence length of model tubules.

    PubMed

    Stevens, Mark J

    2017-07-28

    Young's elastic modulus and the persistence length are calculated for a coarse-grained model of tubule forming polymers. The model uses a wedge shaped composite of particles that previously has been shown to self-assemble into tubules. These calculations demonstrate that the model yields very large persistence lengths (corresponding to 78-126 μm) that are comparable to that observed in experiments for the microtubule lengths accessible to the calculations. The source for the stiffness is the restricted rotation of the monomer due to the excluded volume interactions between bonded macromolecular monomers as well as the binding between monomers. For this reason, large persistence lengths are common in tubule systems with a macromolecule as the monomer. The persistence length increases linearly with increased binding strength in the filament direction. No dependence in the persistence length is found for varying the tubule pitch for geometries with the protofilaments remaining straight.

  7. Pretreatment task persistence predicts smoking cessation outcome.

    PubMed

    Brandon, Thomas H; Herzog, Thaddeus A; Juliano, Laura M; Irvin, Jennifer E; Lazev, Amy B; Simmons, Vani Nath

    2003-08-01

    R. Eisenberger's (1992) learned industriousness theory states that individuals display differing degrees of persistence depending on their history of reinforcement for effortful behavior. These differences may influence the development, maintenance, and cessation of addictive behaviors. In cross-sectional studies, E. P. Quinn, T. H. Brandon, and A. L. Copeland (1996) found that cigarette smokers were less persistent than nonsmokers, and R. A. Brown, C. W. Lejuez, C. W. Kahler, and D. R. Strong (2002) found that smokers who had previously abstained for 3 months were more persistent than those who had never quit. The present study extended these findings by using a prospective design. A pretreatment measure of task persistence (mirror tracing) completed by 144 smokers predicted sustained abstinence throughout 12 months of follow-up. Moreover, persistence predicted outcome independent of other significant predictors: gender, nicotine dependence, negative affect, and self-efficacy.

  8. The long persistence length of model tubules

    NASA Astrophysics Data System (ADS)

    Stevens, Mark J.

    2017-07-01

    Young's elastic modulus and the persistence length are calculated for a coarse-grained model of tubule forming polymers. The model uses a wedge shaped composite of particles that previously has been shown to self-assemble into tubules. These calculations demonstrate that the model yields very large persistence lengths (corresponding to 78-126 μ m) that are comparable to that observed in experiments for the microtubule lengths accessible to the calculations. The source for the stiffness is the restricted rotation of the monomer due to the excluded volume interactions between bonded macromolecular monomers as well as the binding between monomers. For this reason, large persistence lengths are common in tubule systems with a macromolecule as the monomer. The persistence length increases linearly with increased binding strength in the filament direction. No dependence in the persistence length is found for varying the tubule pitch for geometries with the protofilaments remaining straight.

  9. Law of substitution for mixed arrays

    SciTech Connect

    Koudelka, A.J.

    1987-01-01

    The nuclear safety justification of a mixed array of dissimilar fissile units of metal units and dilute solution units, according to Clayton, has been a persistent and nagging problem. Dissimilar uranium metal or dissimilar uranium solution units in a mixed array can also create a modeling nightmare for the nuclear criticality safety engineer. Now, a calculational method known as the Law of Substitution has been developed to ensure that the k/sub eff/ of an array of uranium metal and uranium solution units will satisfy any k/sub eff/ limit set by the nuclear safety engineer. The nuclear criticality safety engineer can utilize the Law of Substitution to safely mix or substitute different uranium metal units, different uranium solution units, and more importantly, uranium metal and dilute UO/sub 2/ solution units in an array. The Law of Substitution is as follows: (1) calculate the k/sub eff/ of each unit type in its own infinite planar array. (2) Determine the edge-to-edge spacing of the infinite planar array of each type of unit to satisfy a desired k/sub eff/. (3) Select the largest edge-to-edge spacing from among the similar units in their infinite planar arrays and use that spacing for the finite or infinite planar array of mixed units.

  10. Mixing processes within the polar night jet

    NASA Technical Reports Server (NTRS)

    Pierce, R. Bradley; Fairlie, T. Duncan; Grose, William L.; Swinbank, Richard; O'Neill, Alan

    1994-01-01

    Lagrangian material line simulations are performed using U.K. Meteorological Office simulated winds and temperatures to examine mixing processes in the middle- and lower-stratospheric polar night jet during the 1992 Southern Hemisphere spring and Northern Hemisphere winter. The Lagrangian simulations are undertaken to provide insight into the effects of mixing within the polar night jet on observations of the polar vortex made by instruments onboard the Upper Atmosphere Research Satellite (UARS) during these periods. A moderate to strong kinematic barrier to large-scale isentropic exchange, similar to the barrier identified in General Circulation Model (GCM) simulations, is identified during both of these periods. Characteristic timescales for mixing by large-scale isentropic motions within the polar night jet range from 20 days in the Southern Hemisphere lower stratosphere to years in the Northern Hemisphere middle stratosphere. The long mixing timescales found in the Northern Hemisphere polar night jet do not persist. Instead, the Northern Hemisphere kinematic barriers are broken down as part of the large-scale stratospheric response to a strong tropospheric blocking event. A series of Lagrangian experiments are conducted to investigate the sensitivity of the kinematic barrier to diabatic effects and to small-scale inertial gravity wave motions. Differential diabatic descent is found to have a significant impact on mixing processes within the Southern Hemisphere middle-stratospheric jet core. The interaction between small-scale displacements by idealized, inertial gravity waves and the large-scale flow is found to have a significant impact on mixing within the polar night jet in both hemispheres. These sensitivity experiments suggest that scales of motion that are unresolved in global assimilated datasets may contribute to mass exchange across the kinematic barrier to large-scale isentropic motion.

  11. ADVANCED MIXING MODELS

    SciTech Connect

    Lee, S; Dimenna, R; Tamburello, D

    2011-02-14

    The process of recovering and processing High Level Waste (HLW) the waste in storage tanks at the Savannah River Site (SRS) typically requires mixing the contents of the tank with one to four mixers (pumps) located within the tank. The typical criteria to establish a mixed condition in a tank are based on the number of pumps in operation and the time duration of operation. To ensure that a mixed condition is achieved, operating times are typically set conservatively long. This approach results in high operational costs because of the long mixing times and high maintenance and repair costs for the same reason. A significant reduction in both of these costs might be realized by reducing the required mixing time based on calculating a reliable indicator of mixing with a suitably validated computer code. The focus of the present work is to establish mixing criteria applicable to miscible fluids, with an ultimate goal of addressing waste processing in HLW tanks at SRS and quantifying the mixing time required to suspend sludge particles with the submersible jet pump. A single-phase computational fluid dynamics (CFD) approach was taken for the analysis of jet flow patterns with an emphasis on the velocity decay and the turbulent flow evolution for the farfield region from the pump. Literature results for a turbulent jet flow are reviewed, since the decay of the axial jet velocity and the evolution of the jet flow patterns are important phenomena affecting sludge suspension and mixing operations. The work described in this report suggests a basis for further development of the theory leading to the identified mixing indicators, with benchmark analyses demonstrating their consistency with widely accepted correlations. Although the indicators are somewhat generic in nature, they are applied to Savannah River Site (SRS) waste tanks to provide a better, physically based estimate of the required mixing time. Waste storage tanks at SRS contain settled sludge which varies in

  12. Mixing in Microfluidic Systems

    NASA Astrophysics Data System (ADS)

    Beskok, A.

    Flow and species transport in micro-scales experience laminar, even Stokes flow conditions. In absence of turbulence, species mixing becomes diffusion dominated, and requires very long mixing length scales (l m ). This creates significant challenges in the design of Lab-on-a-chip (LOC) devices, where mixing of macromolecules and biological species with very low mass diffusivities are often desired. The objectives of this chapter are to introduce concepts relevant to mixing enhancement in microfluidic systems, and guide readers in the design of new mixers via numerical simulations. A distinguishing feature is the identification of flow kinematics that enhance mixing, followed with systematic characterization of mixing as a function of the Schmidt number at fixed kinematic conditions. In this chapter, we briefly review the routes to achieve chaotic advection in Stokes flow, and then illustrate the characteri-zation of a continuous flow chaotic stirrer via appropriate numerical tools, including the Poincaré section, finite time Lyapunov exponent, and mixing index.

  13. The mixing of fluids

    SciTech Connect

    Ottino, J.M.

    1989-01-01

    What do the eruption of Krakatau, the manufacture of puff pastry and the brightness of stars have in common Each involves some aspect of mixing. Mixing also plays a critical role in modern technology. Chemical engineers rely on mixing to ensure that substances react properly, to produce polymer blends that exhibit unique properties and to disperse drag-reducing agents in pipelines. Yet in spite of its of its ubiquity in nature and industry, mixing is only imperfectly under-stood. Indeed, investigators cannot even settle on a common terminology: mixing is often referred to as stirring by oceanographers and geophysicists, as blending by polymer engineers and as agitation by process engineers. Regardless of what the process is called, there is little doubt that it is exceedingly complex and is found in a great variety of systems. In constructing a theory of fluid mixing, for example, one has to take into account fluids that can be miscible or partially miscible and reactive or inert, and flows that are slow and orderly or very fast and turbulent. It is therefore not surprising that no single theory can explain all aspect of mixing in fluids and that straightforward computations usually fail to capture all the important details. Still, both physical experiments and computer simulations can provide insight into the mixing process. Over the past several years the authors and his colleague have taken both approaches in an effort to increase understanding of various aspect of the process-particularly of mixing involving slow flows and viscous fluids such as oils.

  14. Nearly discontinuous chaotic mixing

    SciTech Connect

    Sharp, David Howland; Lim, Hyun K; Yu, Yan; Glimm, James G

    2009-01-01

    A new scientific approach is presented for a broad class of chaotic problems involving a high degree of mixing over rapid time scales. Rayleigh-Taylor and Richtmyer-Meshkov unstable flows are typical of such problems. Microscopic mixing properties such as chemical reaction rates for turbulent mixtures can be obtained with feasible grid resolution. The essential dependence of (some) fluid mixing observables on transport phenomena is observed. This dependence includes numerical as well as physical transport and it includes laminar as well as turbulent transport. A new approach to the mathematical theory for the underlying equations is suggested.

  15. Liquid air mixing system

    NASA Technical Reports Server (NTRS)

    Martin, Robert B. (Inventor)

    1997-01-01

    A device for mixing liquid nitrogen and liquid oxygen to form liquid air. The mixing device consists of a tube for transferring liquid oxygen positioned within a tube for transferring liquid nitrogen. Supply vessels for liquid oxygen and liquid nitrogen are equally pressurized and connected to the appropriate tubes. Liquid oxygen and nitrogen flow from the supply vessels through the respective tubes and are mixed to form liquid air upon exiting the outlets of the tube. The resulting liquid air is transferred to a holding vessel.

  16. Mixing method and apparatus

    DOEpatents

    Green, Norman W.

    1982-06-15

    Method of mixing particulate materials comprising contacting a primary source and a secondary source thereof whereby resulting mixture ensues; preferably at least one of the two sources has enough motion to insure good mixing and the particulate materials may be heat treated if desired. Apparatus for such mixing comprising an inlet for a primary source, a reactor communicating therewith, a feeding means for supplying a secondary source to the reactor, and an inlet for the secondary source. Feeding means is preferably adapted to supply fluidized materials.

  17. Remotely controllable mixing system

    NASA Technical Reports Server (NTRS)

    Belew, R. R. (Inventor)

    1986-01-01

    This invention relates to a remotely controllable mixing system in which a plurality of mixing assemblies are arranged in an annular configuration, and wherein each assembly employs a central chamber and two outer, upper and lower chambers. Valves are positioned between chambers, and these valves for a given mixing assembly are operated by upper and lower control rotors, which in turn are driven by upper and lower drive rotors. Additionally, a hoop is compressed around upper control rotors and a hoop is compressed around lower control rotors to thus insure constant frictional engagement between all control rotors and drive rotors. The drive rollers are driven by a motor.

  18. Drought Persistence in Models and Observations

    NASA Astrophysics Data System (ADS)

    Moon, Heewon; Gudmundsson, Lukas; Seneviratne, Sonia

    2017-04-01

    Many regions of the world have experienced drought events that persisted several years and caused substantial economic and ecological impacts in the 20th century. However, it remains unclear whether there are significant trends in the frequency or severity of these prolonged drought events. In particular, an important issue is linked to systematic biases in the representation of persistent drought events in climate models, which impedes analysis related to the detection and attribution of drought trends. This study assesses drought persistence errors in global climate model (GCM) simulations from the 5th phase of Coupled Model Intercomparison Project (CMIP5), in the period of 1901-2010. The model simulations are compared with five gridded observational data products. The analysis focuses on two aspects: the identification of systematic biases in the models and the partitioning of the spread of drought-persistence-error into four possible sources of uncertainty: model uncertainty, observation uncertainty, internal climate variability and the estimation error of drought persistence. We use monthly and yearly dry-to-dry transition probabilities as estimates for drought persistence with drought conditions defined as negative precipitation anomalies. For both time scales we find that most model simulations consistently underestimated drought persistence except in a few regions such as India and Eastern South America. Partitioning the spread of the drought-persistence-error shows that at the monthly time scale model uncertainty and observation uncertainty are dominant, while the contribution from internal variability does play a minor role in most cases. At the yearly scale, the spread of the drought-persistence-error is dominated by the estimation error, indicating that the partitioning is not statistically significant, due to a limited number of considered time steps. These findings reveal systematic errors in the representation of drought persistence in current

  19. Guidelines for mixed waste minimization

    SciTech Connect

    Owens, C.

    1992-02-01

    Currently, there is no commercial mixed waste disposal available in the United States. Storage and treatment for commercial mixed waste is limited. Host States and compacts region officials are encouraging their mixed waste generators to minimize their mixed wastes because of management limitations. This document provides a guide to mixed waste minimization.

  20. Coupling effect of nodes popularity and similarity on social network persistence

    NASA Astrophysics Data System (ADS)

    Jin, Xiaogang; Jin, Cheng; Huang, Jiaxuan; Min, Yong

    2017-02-01

    Network robustness represents the ability of networks to withstand failures and perturbations. In social networks, maintenance of individual activities, also called persistence, is significant towards understanding robustness. Previous works usually consider persistence on pre-generated network structures; while in social networks, the network structure is growing with the cascading inactivity of existed individuals. Here, we address this challenge through analysis for nodes under a coevolution model, which characterizes individual activity changes under three network growth modes: following the descending order of nodes’ popularity, similarity or uniform random. We show that when nodes possess high spontaneous activities, a popularity-first growth mode obtains highly persistent networks; otherwise, with low spontaneous activities, a similarity-first mode does better. Moreover, a compound growth mode, with the consecutive joining of similar nodes in a short period and mixing a few high popularity nodes, obtains the highest persistence. Therefore, nodes similarity is essential for persistent social networks, while properly coupling popularity with similarity further optimizes the persistence. This demonstrates the evolution of nodes activity not only depends on network topology, but also their connective typology.

  1. Coupling effect of nodes popularity and similarity on social network persistence

    PubMed Central

    Jin, Xiaogang; Jin, Cheng; Huang, Jiaxuan; Min, Yong

    2017-01-01

    Network robustness represents the ability of networks to withstand failures and perturbations. In social networks, maintenance of individual activities, also called persistence, is significant towards understanding robustness. Previous works usually consider persistence on pre-generated network structures; while in social networks, the network structure is growing with the cascading inactivity of existed individuals. Here, we address this challenge through analysis for nodes under a coevolution model, which characterizes individual activity changes under three network growth modes: following the descending order of nodes’ popularity, similarity or uniform random. We show that when nodes possess high spontaneous activities, a popularity-first growth mode obtains highly persistent networks; otherwise, with low spontaneous activities, a similarity-first mode does better. Moreover, a compound growth mode, with the consecutive joining of similar nodes in a short period and mixing a few high popularity nodes, obtains the highest persistence. Therefore, nodes similarity is essential for persistent social networks, while properly coupling popularity with similarity further optimizes the persistence. This demonstrates the evolution of nodes activity not only depends on network topology, but also their connective typology. PMID:28220840

  2. Patterns of persistent HPV infection after treatment for cervical intraepithelial neoplasia (CIN): A systematic review.

    PubMed

    Hoffman, Sarah R; Le, Tam; Lockhart, Alexandre; Sanusi, Ayodeji; Dal Santo, Leila; Davis, Meagan; McKinney, Dana A; Brown, Meagan; Poole, Charles; Willame, Corinne; Smith, Jennifer S

    2017-01-25

    A systematic review of the literature was conducted to determine the estimates of and definitions for human papillomavirus (HPV) persistence in women following treatment of cervical intra-epithelial neoplasia (CIN). A total of 45 studies presented data on post-treatment HPV persistence among 6,106 women. Most studies assessed HPV persistence after loop excision (42%), followed by conization (7%), cryotherapy (11%), laser treatment (4%), interferon-alpha, therapeutic vaccination, and photodynamic therapy (2% each) and mixed treatment (38%). Baseline HPV testing was conducted before or at treatment for most studies (96%). Follow-up HPV testing ranged from 1.5 to 80 months after baseline. Median HPV persistence tended to decrease with increasing follow-up time, declining from 27% at 3 months after treatment to 21% at 6 months, 15% at 12 months, and 10% at 24 months. Post-treatment HPV persistence estimates varied widely and were influenced by patient age, HPV-type, detection method, treatment method, and minimum HPV post-treatment testing interval. Loop excision and conization appeared to outperform cryotherapy procedures in terms of their ability to clear HPV infection. This systematic review provides evidence for the substantial heterogeneity in post-treatment HPV DNA testing practices and persistence estimates.

  3. Mixed-Media Owls

    ERIC Educational Resources Information Center

    Schultz, Kathy

    2010-01-01

    The fun of creating collages is there are unlimited possibilities for the different kinds of materials one can use. In this article, the author describes how her eighth-grade students created an owl using mixed media.

  4. Mixed-Media Owls

    ERIC Educational Resources Information Center

    Schultz, Kathy

    2010-01-01

    The fun of creating collages is there are unlimited possibilities for the different kinds of materials one can use. In this article, the author describes how her eighth-grade students created an owl using mixed media.

  5. Artificial upwelling and mixing

    SciTech Connect

    Not Available

    1989-01-01

    The authors present results related to artificial upwelling and coastal mariculture using deep ocean water and mixing in coastal waters. They discuss the application of research results for marine waste disposal.

  6. The MIXED framework: A novel approach to evaluating mixed-methods rigor.

    PubMed

    Eckhardt, Ann L; DeVon, Holli A

    2017-02-09

    Evaluation of rigor in mixed-methods (MM) research is a persistent challenge due to the combination of inconsistent philosophical paradigms, the use of multiple research methods which require different skill sets, and the need to combine research at different points in the research process. Researchers have proposed a variety of ways to thoroughly evaluate MM research, but each method fails to provide a framework that is useful for the consumer of research. In contrast, the MIXED framework is meant to bridge the gap between an academic exercise and practical assessment of a published work. The MIXED framework (methods, inference, expertise, evaluation, and design) borrows from previously published frameworks to create a useful tool for the evaluation of a published study. The MIXED framework uses an experimental eight-item scale that allows for comprehensive integrated assessment of MM rigor in published manuscripts. Mixed methods are becoming increasingly prevalent in nursing and healthcare research requiring researchers and consumers to address issues unique to MM such as evaluation of rigor.

  7. Asymmetric antiproton debuncher: No bad mixing, more good mixing

    SciTech Connect

    Visnjic, V.

    1994-07-01

    An asymmetric lattice for the Fermilab Antiproton Debuncher is designed. The lattice has zero mixing between the pickups and the kickers (bad mixing) while the mixing in the rest of the machine (good mixing) can be varied (even during the operation of the machine) in order to optimize the stochastic cooling. As an example, a lattice with zero bad mixing and twice the good mixing is presented. The betatron cooling rate in this lattice is twice its present value.

  8. Persistent photosensitivity caused by musk ambrette.

    PubMed

    Zugerman, C

    1981-07-01

    Persistent photosensitivity developed in a man after use of an after-shave lotion containing musk ambrette. His eruption, present over ligh-exposed areas of the face, the "V" area of the neck, and the dorsa of the hands, has persisted for more than three years despite therapy. The patient demonstrated a minimal erythema after an ultraviolet B dose of 5 s, and was strongly ultraviolet A photosensitive to a 2% musk ambrette solution in petrolatum and to the after-shave lotion that contained musk ambrette. A persistent light reactivity induced by musk ambrette has most likely developed in this patient.

  9. Mixing on the Heard Island Plateau during HEOBI

    NASA Astrophysics Data System (ADS)

    Robertson, R.

    2016-12-01

    On the plateau near Heard and McDonald Islands, the water column was nearly always well mixed. Typically, temperature differences between the surface and the bottom, 100-200 m, were less than 0.2oC and often less that 0.1oC. Surface stratification developed through insolation and deep primarily through a combination of upwelling from canyons and over the edge of the plateau and tidal advection. This stratification was primarily removed by a combination of wind and tidal mixing. Persistent winds of 30 knots mixed the upper 20-50 m. Strong wind events, 40-60 knots, mixed the water column to 100-200 m depth, which over the plateau, was often the entire water column. Benthic tidal friction mixed the bottom 30-50 m. Although the water column was unstratified at the two plume sites intensively investigated, tidal velocities were baroclinic, probably due to topographic controls. Tidal advection changed the bottom temperatures by 0.5oC within 8 hours, more than doubling the prior stratification. Wind mixing quickly homogenized the water column, resulting in the surface often showing the deeper upwelling and advective events. Although acoustic plumes with bubbles were observed in the water column, there was no evidence of geothermal vents or geothermal influence on temperatures. Mixing by bubbles rising in the water column was indistinguishable from the wind and tidal mixing, although the strongest upward vertical velocities were observed at the sites of these acoustic/bubble plumes.

  10. Persistent Ice on Lake Superior

    NASA Image and Video Library

    2017-09-27

    Though North America is a full month into astronomical spring, the Great Lakes have been slow to give up on winter. As of April 22, 2014, the Great Lakes were 33.9 percent ice covered. The lake they call Superior dominated the pack. In the early afternoon on April 20, 2014, the Moderate Resolution Imaging Spectroradiometer (MODIS) on NASA’s Aqua satellite captured this natural-color image of Lake Superior, which straddles the United States–Canada border. At the time Aqua passed over, the lake was 63.5 percent ice covered, according to the NOAA Great Lakes Environmental Research Lab (GLERL). Averaged across Lake Superior, ice was 22.6 centimeters (8.9 inches) thick; it was as much as twice that thickness in some locations. GLERL researcher George Leshkevich affirmed that ice cover this spring is significantly above normal. For comparison, Lake Superior had 3.6 percent ice cover on April 20, 2013; in 2012, ice was completely gone by April 12. In the last winter that ice cover grew so thick on Lake Superior (2009), it reached 93.7 percent on March 2 but was down to 6.7 percent by April 21. Average water temperatures on all of the Great Lakes have been rising over the past 30 to 40 years and ice cover has generally been shrinking. (Lake Superior ice was down about 79 percent since the 1970s.) But chilled by persistent polar air masses throughout the 2013-14 winter, ice cover reached 88.4 percent on February 13 and 92.2 percent on March 6, 2014, the second highest level in four decades of record-keeping. Air temperatures in the Great Lakes region were well below normal for March, and the cool pattern is being reinforced along the coasts because the water is absorbing less sunlight and warming less than in typical spring conditions. The graph below, based on data from Environment Canada, shows the 2014 conditions for all of the Great Lakes in mid-April compared to the past 33 years. Lake Superior ice cover got as high as 95.3 percent on March 19. By April 22, it was

  11. Persistence of Pigment Production by Yeast Isolates Grown on CHROMagar Candida Medium

    PubMed Central

    Hospenthal, Duane R.; Murray, Clinton K.; Beckius, Miriam L.; Green, Judith A.; Dooley, David P.

    2002-01-01

    We evaluated the persistence of pigmentation in yeast isolates grown on the chromogenic medium CHROMagar Candida over 7 days. Candida, Cryptococcus, and Trichosporon isolates were inoculated alone or mixed onto duplicate sets of plates and incubated at 30 and 35°C. Candida albicans and Candida krusei were readily identified throughout the reading period, but Candida glabrata was difficult to differentiate from other species until the 3- or 4-day time point. Candida tropicalis produced colonies similar to those of rare Cryptococcus and Trichosporon species, and mixed cultures were often difficult to identify as such. PMID:12454192

  12. Longitudinal persistence with secondary prevention therapies relative to patient risk after myocardial infarction

    PubMed Central

    Shore, Supriya; Jones, Philip G.; Maddox, Thomas M.; Bradley, Steven M.; Stolker, Joshua M.; Arnold, Suzanne V.; Parashar, Susmita; Peterson, Pamela; Bhatt, Deepak L.; Spertus, John; Ho, P. Michael

    2016-01-01

    Background Prior studies have demonstrated that high-risk AMI patients are less likely to receive guideline-directed medications during hospitalization. It is unknown if this paradox persists following discharge. We aimed to assess if persistence with guideline-directed medications post-discharge varies by patients’ risk following acute myocardial infarction (AMI). Methods Data were analyzed from two prospective, multicenter U.S. AMI registries. The primary outcome was persistence with all prescribed guideline-directed medications (aspirin, beta-blockers, statins, angiotensin-antagonists) at 1, 6, and 12-months post-discharge. The association between risk and medication persistence post-discharge was assessed using multivariable mixed-effect models. Results Among 6434 AMI patients discharged home, 2824 were considered low-risk, 2014 intermediate-risk and 1596 high-risk for death based upon their GRACE 6-month risk score. High-risk was associated with a lower likelihood of receiving all appropriate therapies at discharge compared with low-risk patients (RR 0.90; 95% CI 0.87–0.94). At 12-months, the rate of persistence with all prescribed therapies was 61.5%, 57.9% and 45.9% among low-, intermediate- and high-risk patients respectively. After multivariable adjustment, high-risk was associated with lower persistence with all prescribed medications (RR 0.87; 95% CI 0.82–0.92) over follow-up. Similar associations were seen for individual medications. Over the 5 years of the study, persistence with prescribed therapies post-discharge improved modestly among high-risk patients (RR 1.05; 95% CI 1.03–1.08 per year). Conclusion High-risk AMI patients have a lower likelihood of persistently taking prescribed medications post-discharge as compared with low-risk patients. Continued efforts are needed to improve the use of guideline-directed medications in high-risk patients. PMID:25801001

  13. Persistence of Antibiotic Resistance Plasmids in Biofilms

    DTIC Science & Technology

    2014-10-01

    useful in the care of patients with combat-related wound infections. 15. SUBJECT TERMS Antibiotic resistance, plasmid, biofilm, coevolution , bacteria...Antibiotic!resistance,!plasmid,!biofilm,! coevolution ,!bacteria,!wound!infections! ! ! ! 3! 3. OVERALL PROJECT SUMMARY: The! successful! persistence

  14. The persistent stereotype: children's images of scientists

    NASA Astrophysics Data System (ADS)

    Emens McAdam, Janice

    1990-03-01

    Through their reading children learn to regard scientists as eccentrics. It is shown that this stereotype has persisted for over thirty years and affects many adult attitudes. Some methods of breaking the author-reader cycle are suggested.

  15. Stimuli, Reinforcers, and the Persistence of Behavior

    ERIC Educational Resources Information Center

    Nevin, John A.

    2009-01-01

    This article reviews evidence from basic and translational research with pigeons and humans suggesting that the persistence of operant behavior depends on the contingency between stimuli and reinforcers, and considers some implications for clinical interventions. (Contains 4 figures.)

  16. Stimuli, Reinforcers, and the Persistence of Behavior

    ERIC Educational Resources Information Center

    Nevin, John A.

    2009-01-01

    This article reviews evidence from basic and translational research with pigeons and humans suggesting that the persistence of operant behavior depends on the contingency between stimuli and reinforcers, and considers some implications for clinical interventions. (Contains 4 figures.)

  17. Atypical persistence of tunica vasculosa lentis.

    PubMed

    Kumar, Ashima V; Chhabra, Manpreet S; Mets, Marilyn B

    2008-01-01

    The authors report an unusual case of persistent tunica vasculosa lentis in a patient with minimal retinopathy of prematurity (ROP). A 3-month-old male infant who had been born at 31 weeks' gestation presented with a significant amount of persistent tunica vasculosa lentis and arteriolar tortuosity with minimal ROP and no plus disease. After weekly observation and no surgical intervention, the arteriolar tortuosity lessened but the tunica vasculosa lentis persisted. Persistent tunica vasculosa lentis can be mistaken for iris vascular engorgement, suggesting plus disease and high-risk prethreshold ROP. Differentiation between tunica vasculosa lentis and iris vascular engorgement, as well as correct diagnosis of plus disease, is critical when considering laser treatment for high-risk prethreshold ROP.

  18. Persistent Pain May Lead to Memory Troubles

    MedlinePlus

    ... fullstory_166304.html Persistent Pain May Lead to Memory Troubles Study even suggests link between chronic aches ... to changes in the brain that contribute to memory problems. The findings may also point to new ...

  19. Mixing of Supersonic Streams

    NASA Technical Reports Server (NTRS)

    Hawk, C. W.; Landrum, D. B.; Muller, S.; Turner, M.; Parkinson, D.

    1998-01-01

    The Strutjet approach to Rocket Based Combined Cycle (RBCC) propulsion depends upon fuel-rich flows from the rocket nozzles and turbine exhaust products mixing with the ingested air for successful operation in the ramjet and scramjet modes. It is desirable to delay this mixing process in the air-augmented mode of operation present during low speed flight. A model of the Strutjet device has been built and is undergoing test to investigate the mixing of the streams as a function of distance from the Strutjet exit plane during simulated low speed flight conditions. Cold flow testing of a 1/6 scale Strutjet model is underway and nearing completion. Planar Laser Induced Fluorescence (PLIF) diagnostic methods are being employed to observe the mixing of the turbine exhaust gas with the gases from both the primary rockets and the ingested air simulating low speed, air augmented operation of the RBCC. The ratio of the pressure in the turbine exhaust duct to that in the rocket nozzle wall at the point of their intersection is the independent variable in these experiments. Tests were accomplished at values of 1.0, 1.5 and 2.0 for this parameter. Qualitative results illustrate the development of the mixing zone from the exit plane of the model to a distance of about 10 rocket nozzle exit diameters downstream. These data show the mixing to be confined in the vertical plane for all cases, The lateral expansion is more pronounced at a pressure ratio of 1.0 and suggests that mixing with the ingested flow would be likely beginning at a distance of 7 nozzle exit diameters downstream of the nozzle exit plane.

  20. Mixing of Supersonic Streams

    NASA Technical Reports Server (NTRS)

    Hawk, C. W.; Landrum, D. B.; Muller, S.; Turner, M.; Parkinson, D.

    1998-01-01

    The Strutjet approach to Rocket Based Combined Cycle (RBCC) propulsion depends upon fuel-rich flows from the rocket nozzles and turbine exhaust products mixing with the ingested air for successful operation in the ramjet and scramjet modes. It is desirable to delay this mixing process in the air-augmented mode of operation present during low speed flight. A model of the Strutjet device has been built and is undergoing test to investigate the mixing of the streams as a function of distance from the Strutjet exit plane during simulated low speed flight conditions. Cold flow testing of a 1/6 scale Strutjet model is underway and nearing completion. Planar Laser Induced Fluorescence (PLIF) diagnostic methods are being employed to observe the mixing of the turbine exhaust gas with the gases from both the primary rockets and the ingested air simulating low speed, air augmented operation of the RBCC. The ratio of the pressure in the turbine exhaust duct to that in the rocket nozzle wall at the point of their intersection is the independent variable in these experiments. Tests were accomplished at values of 1.0, 1.5 and 2.0 for this parameter. Qualitative results illustrate the development of the mixing zone from the exit plane of the model to a distance of about 19 equivalent rocket nozzle exit diameters downstream. These data show the mixing to be confined in the vertical plane for all cases, The lateral expansion is more pronounced at a pressure ratio of 1.0 and suggests that mixing with the ingested flow would be likely beginning at a distance of 7 nozzle exit diameters downstream of the nozzle exit plane.

  1. Mixing of Supersonic Streams

    NASA Technical Reports Server (NTRS)

    Hawk, C. W.; Landrum, D. B.; Muller, S.; Turner, M.; Parkinson, D.

    1998-01-01

    The Strutjet approach to Rocket Based Combined Cycle (RBCC) propulsion depends upon fuel-rich flows from the rocket nozzles and turbine exhaust products mixing with the ingested air for successful operation in the ramjet and scramjet modes. It is desirable to delay this mixing process in the air-augmented mode of operation present during low speed flight. A model of the Strutjet device has been built and is undergoing test to investigate the mixing of the streams as a function of distance from the Strutjet exit plane during simulated low speed flight conditions. Cold flow testing of a 1/6 scale Strutjet model is underway and nearing completion. Planar Laser Induced Fluorescence (PLIF) diagnostic methods are being employed to observe the mixing of the turbine exhaust gas with the gases from both the primary rockets and the ingested air simulating low speed, air augmented operation of the RBCC. The ratio of the pressure in the turbine exhaust duct to that in the rocket nozzle wall at the point of their intersection is the independent variable in these experiments. Tests were accomplished at values of 1.0, 1.5 and 2.0 for this parameter. Qualitative results illustrate the development of the mixing zone from the exit plane of the model to a distance of about 19 equivalent rocket nozzle exit diameters downstream. These data show the mixing to be confined in the vertical plane for all cases, The lateral expansion is more pronounced at a pressure ratio of 1.0 and suggests that mixing with the ingested flow would be likely beginning at a distance of 7 nozzle exit diameters downstream of the nozzle exit plane.

  2. Persistent homology analysis of phase transitions

    NASA Astrophysics Data System (ADS)

    Donato, Irene; Gori, Matteo; Pettini, Marco; Petri, Giovanni; De Nigris, Sarah; Franzosi, Roberto; Vaccarino, Francesco

    2016-05-01

    Persistent homology analysis, a recently developed computational method in algebraic topology, is applied to the study of the phase transitions undergone by the so-called mean-field XY model and by the ϕ4 lattice model, respectively. For both models the relationship between phase transitions and the topological properties of certain submanifolds of configuration space are exactly known. It turns out that these a priori known facts are clearly retrieved by persistent homology analysis of dynamically sampled submanifolds of configuration space.

  3. Persistent and Recurrent Clostridium difficile Colitis

    PubMed Central

    Cole, Shola A.; Stahl, Thomas J.

    2015-01-01

    Clostridium difficile infection (CDI) is the most frequent cause of nosocomial diarrhea. It has become a significant dilemma in the treatment of patients, and causes increasing morbidity that, in extreme cases, may result in death. Persistent and recurrent disease hamper attempts at eradication of this infection. Escalating levels of treatment and novel therapeutics are being utilized and developed to treat CDI. Further trials are warranted to definitively determine what protocols can be used to treat persistent and recurrent disease. PMID:26034401

  4. Persistent homology analysis of phase transitions.

    PubMed

    Donato, Irene; Gori, Matteo; Pettini, Marco; Petri, Giovanni; De Nigris, Sarah; Franzosi, Roberto; Vaccarino, Francesco

    2016-05-01

    Persistent homology analysis, a recently developed computational method in algebraic topology, is applied to the study of the phase transitions undergone by the so-called mean-field XY model and by the ϕ^{4} lattice model, respectively. For both models the relationship between phase transitions and the topological properties of certain submanifolds of configuration space are exactly known. It turns out that these a priori known facts are clearly retrieved by persistent homology analysis of dynamically sampled submanifolds of configuration space.

  5. Wolf population persistence in real life

    USGS Publications Warehouse

    Mech, L.D.; Liberg, O.

    2005-01-01

    Wolf (Canis lupus) populations tend to be resilient and to persist for long periods, and several characteristics contribute to their resilience and persistence: (1) age of first reproduction (2-3 years), (2) high annual litter size (mean = 6), (3) low dispersal age (1-3 years), and (4) long potential dispersal distance (< 880 km). The only documented factor leading to extinction of well established wolf populations with sufficient food is deliberate poisoning, although conceivably disease could have such an effect.

  6. [Therapeutic approach in persistent diabetic macular edema].

    PubMed

    Brănişteanu, Daniel; Moraru, Andreea

    2014-01-01

    Terminology of persistent diabetic macular edema has been initially reserved to cases unresponsive to conventional laser photocoagulation according to ETDRS criteria. While knowledge about pathophysiology of macular edema evolved and new drugs became available, the terminology of persistent diabetic macular edema expanded to include resistance to most current therapies. The purpose of this paper is to review medical and surgical options in the treatment of such difficult cases according to literature data and personal experience.

  7. Persistence of the Lower Stratospheric Polar Vortices

    NASA Technical Reports Server (NTRS)

    Waugh, Darryn W.; Randel, William J.; Pawson, Steven; Newman, Paul A.; Nash, Eric R.

    1999-01-01

    The persistence of the Arctic and Antarctic lower stratospheric vortices is examined over the period 1958 to 1998. Three different vortex-following diagnostics (two using potential vorticity and one based solely on the zonal winds) are compared, and shown to give very similar results for the break up date. The variability in the timing of the breakup of each vortex is qualitatively the same: there are large interannual variations together with smaller decadal-scale variations and there is a significant increase in the persistence since the mid-1980s (all variations are larger for the Arctic vortex). Also, in both hemispheres there is a high correlation between the persistence and the strength and coldness of the spring vortex, with all quantities having the same interannual and decadal variability. However, there is no such correlation between the persistence and the characteristics of the mid-winter vortex. In the northern hemisphere there is also a high correlation between the vortex persistence and the upper tropospheric/lower stratospheric eddy heat flux averaged over the two months prior to the breakup. This indicates that the variability in the wave activity entering the stratosphere over late-winter to early-spring plays a key role in the variability of the vortex persistence (and spring polar temperatures) on both interannual and decadal time scales. However, the decadal variation in the Arctic vortex coldness and persistence for the 1990's falls outside the range of natural variability, while this is not the case for the eddy heat flux. This suggests that the recent increase in vortex persistence is not due solely to changes in the wave activity entering the stratosphere.

  8. Persistence of the Lower Stratospheric Polar Vortices

    NASA Technical Reports Server (NTRS)

    Waugh, Darryn W.; Randel, William J.; Pawson, Steven; Newman, Paul A.; Nash, Eric R.

    1999-01-01

    The persistence of the Arctic and Antarctic lower stratospheric vortices is examined over the period 1958 to 1998. Three different vortex-following diagnostics (two using potential vorticity and one based solely on the zonal winds) are compared, and shown to give very similar results for the break up date. The variability in the timing of the breakup of each vortex is qualitatively the same: there are large interannual variations together with smaller decadal-scale variations and there is a significant increase in the persistence since the mid-1980s (all variations are larger for the Arctic vortex). Also, in both hemispheres there is a high correlation between the persistence and the strength and coldness of the spring vortex, with all quantities having the same interannual and decadal variability. However, there is no such correlation between the persistence and the characteristics of the mid-winter vortex. In the northern hemisphere there is also a high correlation between the vortex persistence and the upper tropospheric/lower stratospheric eddy heat flux averaged over the two months prior to the breakup. This indicates that the variability in the wave activity entering the stratosphere over late-winter to early-spring plays a key role in the variability of the vortex persistence (and spring polar temperatures) on both interannual and decadal time scales. However, the decadal variation in the Arctic vortex coldness and persistence for the 1990's falls outside the range of natural variability, while this is not the case for the eddy heat flux. This suggests that the recent increase in vortex persistence is not due solely to changes in the wave activity entering the stratosphere.

  9. Persistent homology in graph power filtrations

    PubMed Central

    Marchette, David J.

    2016-01-01

    The persistence of homological features in simplicial complex representations of big datasets in Rn resulting from Vietoris–Rips or Čech filtrations is commonly used to probe the topological structure of such datasets. In this paper, the notion of homological persistence in simplicial complexes obtained from power filtrations of graphs is introduced. Specifically, the rth complex, r ≥ 1, in such a power filtration is the clique complex of the rth power Gr of a simple graph G. Because the graph distance in G is the relevant proximity parameter, unlike a Euclidean filtration of a dataset where regional scale differences can be an issue, persistence in power filtrations provides a scale-free insight into the topology of G. It is shown that for a power filtration of G, the girth of G defines an r range over which the homology of the complexes in the filtration are guaranteed to persist in all dimensions. The role of chordal graphs as trivial homology delimiters in power filtrations is also discussed and the related notions of ‘persistent triviality’, ‘transient noise’ and ‘persistent periodicity’ in power filtrations are introduced. PMID:27853540

  10. NIR persistent luminescence of lanthanide ion-doped rare-earth oxycarbonates: the effect of dopants.

    PubMed

    Caratto, Valentina; Locardi, Federico; Costa, Giorgio Andrea; Masini, Roberto; Fasoli, Mauro; Panzeri, Laura; Martini, Marco; Bottinelli, Emanuela; Gianotti, Enrica; Miletto, Ivana

    2014-10-22

    A series of luminescent rare-earth ion-doped hexagonal II-type Gd oxycarbonate phosphors Gd2-xRExO2CO3 (RE = Eu(3+), Yb(3+), Dy(3+)) have been successfully synthesized by thermal decomposition of the corresponding mixed oxalates. The Yb(3+) doped Gd-oxycarbonate has evidenced a high persistent luminescence in the NIR region, that is independent from the temperature and makes this materials particular attractive as optical probes for bioimaging.

  11. Mixed waste management options

    SciTech Connect

    Owens, C.B.; Kirner, N.P.

    1991-12-31

    Disposal fees for mixed waste at proposed commercial disposal sites have been estimated to be $15,000 to $40,000 per cubit foot. If such high disposal fees are imposed, generators may be willing to apply extraordinary treatment or regulatory approaches to properly dispose of their mixed waste. This paper explores the feasibility of several waste management scenarios and attempts to answer the question: Can mixed waste be managed out of existence? Existing data on commercially generated mixed waste streams are used to identify the realm of mixed waste known to be generated. Each waste stream is evaluated from both a regulatory and technical perspective in order to convert the waste into a strictly low-level radioactive or a hazardous waste. Alternative regulatory approaches evaluated in this paper include a delisting petition, no migration petition, and a treatability variance. For each waste stream, potentially available treatment options are identified that could lead to these variances. Waste minimization methodology and storage for decay are also considered. Economic feasibility of each option is discussed broadly.

  12. [Mixed states and schizophrenia].

    PubMed

    Fakra, E; Belzeaux, R; Pringuey, D; Cermolacce, M; Corréard, N; Micoulaud-Franchi, J-A; Azorin, J-M

    2013-12-01

    Because of their compilation of contrasted symptoms and their variable clinical presentation, mixed episodes have been withdrawn from the DSM. However, mixed states question not only the bonds between depression and mania, but also the distinction between bipolar disorders and schizophrenia. Indeed, doubts about the dichotomy introduced by Kraepelin between bipolar disorders and schizophrenia is as old as the nosolgy itself, as attest the later works of this author revealing his hesitations on his own classification. But findings here reviewed issued from recent technical advances, particularly in the imaging and genetic fields, offer a better understanding of the boundaries between these two disorders. Yet, when confronted to an acute episode, clinicians may find it challenging to distinguish a mixed state from a schizophrenic relapse. Indeed, there is no pathognomonic manifestation allowing to retain a diagnosis with confidence. The physician will therefore have to identify a pattern of signs, which will orient his assessment with no certainty. Thus, negative rather than affective or psychotic symptomatology appears to be useful in discriminating schizophrenia (or schizoaffective) disorders from mixed mania. However, a conclusion during this acute stage appears in definitive a formal exercise, first because the final diagnosis will only be ascertained once the symptoms are amended, and second because, according to our classifications, a mood episode, including mania and mixed mania, can be observed without ruling out the diagnosis of schizophrenia. Copyright © 2013 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.

  13. PERSISTENT BREAST PAIN FOLLOWING BREAST CANCER SURGERY IS ASSOCIATED WITH PERSISTENT SENSORY CHANGES, PAIN INTERFERENCE, AND FUNCTIONAL IMPAIRMENTS

    PubMed Central

    Langford, Dale J.; Paul, Steven M.; West, Claudia; Levine, Jon D.; Hamolsky, Deborah; Elboim, Charles; Schmidt, Brian L.; Cooper, Bruce A.; Abrams, Gary; Aouizerat, Bradley E.; Miaskowski, Christine

    2014-01-01

    Inter-individual variability exists in persistent breast pain following breast cancer surgery. Recently, we used growth mixture modeling to identify three subgroups of women (n=398) with distinct persistent breast pain trajectories over six months following surgery (i.e., Mild, Moderate, Severe). Purposes of this study were to identify demographic and clinical characteristics that differed among the breast pain classes and, using linear mixed effects modeling, determine how changes over time, in sensitivity in the breast scar area, pain qualities, pain interference, and hand and arm function differed among these classes. Several demographic and clinical characteristics differentiated the breast pain classes. Of note, 60% to 80% of breast scar sites tested were much less sensitive than the unaffected breast. Significant group effects were observed for pain qualities and interference scores, such that, on average, women in the Severe Pain class reported higher scores than women in the Moderate Pain class. In addition, women in the Moderate Pain class reported higher scores than women in the Mild Pain class. Compared to the Mild Pain class, women in the Severe Pain class had significantly impaired grip strength and women in the Moderate and Severe Pain classes had impaired flexion and abduction. PMID:25439318

  14. Antihypertensive drug prescribing and persistence among new elderly users: implications for persistence improvement interventions.

    PubMed

    Tu, Karen; Anderson, Laura N; Butt, Debra A; Quan, Hude; Hemmelgarn, Brenda R; Campbell, Norm R; McAlister, Finlay A

    2014-06-01

    The objective of this study was to examine persistence rates and factors influencing persistence for new elderly users of antihypertensive drugs. We conducted a population-based cohort study in Ontario of adults aged 66 years or older to identify new users of antihypertensive medications between 1999 and 2010. Two-year therapy and class persistence were defined as persistence on any antihypertensive medication and persistence only on the same antihypertensive medication class, respectively. From 1999-2010, the prevalence of antihypertensive drug use increased from 47.8%-60.5% (P < 0.0001). Persistence was evaluated in 420,148 new users of antihypertensive drugs. After 2 years, therapy persistence was 58.9% and varied according to initial class prescribed, from 52.3% for diuretics to 64.1% for angiotensin-converting enzyme inhibitors. Class persistence ranged from 25.3% for diuretics to 35.8% for angiotensin II receptor blockers. Therapy persistence rates were greater in new users from more recent years (adjusted odds ratio [aOR], 1.24; 95% confidence interval [CI], 1.21-1.27). Subgroups that demonstrated poorer persistence included patients older than 75 years (aOR, 0.95; 95% CI, 0.94-0.96), those with lowest neighbourhood income quintile (aOR, 0.81; 95% CI, 0.80-0.83 compared with the highest quintile), those from urban vs rural areas (aOR, 0.83; 95% CI, 0.81-0.84), and those who started on diuretics as initial monotherapy compared with all other drug classes. Although 2-year therapy and class persistence were low for new users of antihypertensive drugs, improvements have occurred over the past decade. Our data highlight subgroups to target for future persistence improvement interventions. Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  15. Natural convective mixing flows

    NASA Astrophysics Data System (ADS)

    Ramos, Eduardo; de La Cruz, Luis; del Castillo, Luis

    1998-11-01

    Natural convective mixing flows. Eduardo Ramos and Luis M. de La Cruz, National University of Mexico and Luis Del Castillo San Luis Potosi University. The possibility of mixing a fluid with a natural convective flow is analysed by solving numerically the mass, momentum and energy equations in a cubic container. Two opposite vertical walls of the container are assumed to have temperatures that oscillate as functions of time. The phase of the oscillations is chosen in such a way that alternating corrotating vortices are formed in the cavity. The mixing efficiency of this kind of flow is examined with a Lagrangian tracking technique. This work was partially financed by CONACyT-Mexico project number GE0044

  16. Remotely controllable mixing system

    NASA Technical Reports Server (NTRS)

    Belew, Robert R. (Inventor)

    1987-01-01

    A remotely controllable mixing system (210) in which a plurality of mixing assemblies (10a-10e) are arranged in an annular configuration, and wherein each assembly (10) employs a central chamber (16) and two outer, upper and lower, chambers (12, 14). Valves (18, 20) are positioned between chambers, and these valves (18, 20) for a given mixing assembly (10) are operated by upper and lower control rotors (29), which in turn are driven by upper and lower drive rotors (270, 270b). Additionally, a hoop (278) is compressed around upper control rotors (29) and a hoop (278b) is compressed around lower control rotors (29) to thus insure constant frictional engagement between all control rotors (29) and drive rotors (270, 270b). The drive rollers (270, 270b) are driven by a motor (213).

  17. Dilution jet mixing program

    NASA Technical Reports Server (NTRS)

    Srinivasan, R.; Coleman, E.; Johnson, K.

    1984-01-01

    Parametric tests were conducted to quantify the mixing of opposed rows of jets (two-sided injection) in a confined cross flow. Results show that jet penetrations for two sided injections are less than that for single-sided injections, but the jet spreading rates are faster for a given momentum ratio and orifice plate. Flow area convergence generally enhances mixing. Mixing characteristics with asymmetric and symmetric convergence are similar. For constant momentum ratio, the optimum S/H(0) with in-line injections is one half the optimum value for single sided injections. For staggered injections, the optimum S/H(0) is twice the optimum value for single-sided injection. The correlations developed predicted the temperature distributions within first order accuracy and provide a useful tool for predicting jet trajectory and temperature profiles in the dilution zone with two-sided injections.

  18. Mixed waste: Proceedings

    SciTech Connect

    Moghissi, A.A.; Blauvelt, R.K.; Benda, G.A.; Rothermich, N.E.

    1993-12-31

    This volume contains the peer-reviewed and edited versions of papers submitted for presentation a the Second International Mixed Waste Symposium. Following the tradition of the First International Mixed Waste Symposium, these proceedings were prepared in advance of the meeting for distribution to participants. The symposium was organized by the Mixed Waste Committee of the American Society of Mechanical Engineers. The topics discussed at the symposium include: stabilization technologies, alternative treatment technologies, regulatory issues, vitrification technologies, characterization of wastes, thermal technologies, laboratory and analytical issues, waste storage and disposal, organic treatment technologies, waste minimization, packaging and transportation, treatment of mercury contaminated wastes and bioprocessing, and environmental restoration. Individual abstracts are catalogued separately for the data base.

  19. "A pesar de todo" (Despite Everything): The Persistence of Latina Graduate Engineering Students at a Hispanic-Serving Institution

    ERIC Educational Resources Information Center

    Aguirre-Covarrubias, Sandra; Arellano, Eduardo; Espinoza, Penelope

    2015-01-01

    This chapter discusses a mixed-methods study of personal and programmatic factors that affected persistence of Latina graduate engineering students at a Hispanic-serving institution (HSI). The study's findings enabled us to share recommendations that may be useful to HSIs and other colleges and universities.

  20. Archaeal Persisters: Persister Cell Formation as a Stress Response in Haloferax volcanii.

    PubMed

    Megaw, Julianne; Gilmore, Brendan F

    2017-01-01

    Persister cells are phenotypic variants within a microbial population, which are dormant and transiently tolerant to stress. Persistence has been studied extensively in bacteria, and in eukaryotes to a limited extent, however, it has never been observed in archaea. Using the model haloarchaeon, Haloferax volcanii DS2, we demonstrated persister cell formation in this domain, with time-kill curves exhibiting a characteristic biphasic pattern following starvation or exposure to lethal concentrations of various biocidal compounds. Repeated challenges of surviving cells showed that, as with bacteria, persister formation in H. volcanii was not heritable. Additionally, as previously shown with bacteria, persister formation in H. volcanii was suppressed by exogenous indole. The addition of spent culture media to assays conducted on planktonic cells showed that H. volcanii-conditioned media stimulated persistence, whereas conditioned media of other haloarchaea or halophilic bacteria did not, suggesting the involvement of a species-specific signal. Using a TLC overlay assay, the quorum sensing bioreporter Agrobacterium tumefaciens ATCC BAA-2240 detected the presence of C4 and C6 acyl homoserine lactone-like signal molecules in a H. volcanii culture extract. While synthetic bacterial AHLs did not induce persistence, this is potentially due to structural differences between bacterial and archaeal signals, and does not discount a quorum sensing component in haloarchaeal persister formation. The observation of persister cell formation by this haloarchaeon may provide some insights into the survival of these organisms in stressful or dynamic environments.

  1. Archaeal Persisters: Persister Cell Formation as a Stress Response in Haloferax volcanii

    PubMed Central

    Megaw, Julianne; Gilmore, Brendan F.

    2017-01-01

    Persister cells are phenotypic variants within a microbial population, which are dormant and transiently tolerant to stress. Persistence has been studied extensively in bacteria, and in eukaryotes to a limited extent, however, it has never been observed in archaea. Using the model haloarchaeon, Haloferax volcanii DS2, we demonstrated persister cell formation in this domain, with time-kill curves exhibiting a characteristic biphasic pattern following starvation or exposure to lethal concentrations of various biocidal compounds. Repeated challenges of surviving cells showed that, as with bacteria, persister formation in H. volcanii was not heritable. Additionally, as previously shown with bacteria, persister formation in H. volcanii was suppressed by exogenous indole. The addition of spent culture media to assays conducted on planktonic cells showed that H. volcanii-conditioned media stimulated persistence, whereas conditioned media of other haloarchaea or halophilic bacteria did not, suggesting the involvement of a species-specific signal. Using a TLC overlay assay, the quorum sensing bioreporter Agrobacterium tumefaciens ATCC BAA-2240 detected the presence of C4 and C6 acyl homoserine lactone-like signal molecules in a H. volcanii culture extract. While synthetic bacterial AHLs did not induce persistence, this is potentially due to structural differences between bacterial and archaeal signals, and does not discount a quorum sensing component in haloarchaeal persister formation. The observation of persister cell formation by this haloarchaeon may provide some insights into the survival of these organisms in stressful or dynamic environments. PMID:28871247

  2. Mixed crystal organic scintillators

    DOEpatents

    Zaitseva, Natalia P; Carman, M Leslie; Glenn, Andrew M; Hamel, Sebastien; Hatarik, Robert; Payne, Stephen A; Stoeffl, Wolfgang

    2014-09-16

    A mixed organic crystal according to one embodiment includes a single mixed crystal having two compounds with different bandgap energies, the organic crystal having a physical property of exhibiting a signal response signature for neutrons from a radioactive source, wherein the signal response signature does not include a significantly-delayed luminescence characteristic of neutrons interacting with the organic crystal relative to a luminescence characteristic of gamma rays interacting with the organic crystal. According to one embodiment, an organic crystal includes bibenzyl and stilbene or a stilbene derivative, the organic crystal having a physical property of exhibiting a signal response signature for neutrons from a radioactive source.

  3. Mixing navigation on networks

    NASA Astrophysics Data System (ADS)

    Zhou, Tao

    2008-05-01

    In this article, we propose a mixing navigation mechanism, which interpolates between random-walk and shortest-path protocol. The navigation efficiency can be remarkably enhanced via a few routers. Some advanced strategies are also designed: For non-geographical scale-free networks, the targeted strategy with a tiny fraction of routers can guarantee an efficient navigation with low and stable delivery time almost independent of network size. For geographical localized networks, the clustering strategy can simultaneously increase efficiency and reduce the communication cost. The present mixing navigation mechanism is of significance especially for information organization of wireless sensor networks and distributed autonomous robotic systems.

  4. Turbulence and Interfacial Mixing

    SciTech Connect

    Glimm, James; Li, Xiaolin

    2005-03-15

    The authors study mix from analytical and numerical points of view. These investigations are linked. The analytical studies (in addition to laboratory experiments) provide bench marks for the direct simulation of mix. However, direct simulation is too detailed to be useful and to expensive to be practical. They also consider averaged equations. Here the major issue is the validation of the closure assumptions. They appeal to the direct simulation methods for this step. They have collaborated with several NNSA teams; moreover, Stony Brook alumni (former students, faculty and research collaborators) presently hold staff positions in NNSA laboratories.

  5. Atomization and Mixing Study

    NASA Technical Reports Server (NTRS)

    Ferrenberg, A.; Hunt, K.; Duesberg, J.

    1985-01-01

    The primary objective was the obtainment of atomization and mixing performance data for a variety of typical liquid oxygen/hydrocarbon injector element designs. Such data are required to establish injector design criteria and to provide critical inputs to liquid rocket engine combustor performance and stability analysis, and computational codes and methods. Deficiencies and problems with the atomization test equipment were identified, and action initiated to resolve them. Test results of the gas/liquid mixing tests indicated that an assessment of test methods was required. A series of 71 liquid/liquid tests were performed.

  6. Atomization and mixing study

    NASA Technical Reports Server (NTRS)

    Ferrenberg, A.; Jaqua, V. W.

    1983-01-01

    The state of the art in atomization and mixing for triplet, pentad, and coaxial injectors is described. Injectors that are applicable for LOX/hydrocarbon propellants and main chamber and fuel rich preburner/gas generator mixture ratios are of special interest. Various applicable correlating equations and parameters as well as test data found in the literature are presented. The validity, utility, and important aspects of these data and correlations are discussed and the measurement techniques used are evaluated. Propellant mixing tests performed are described and summarized, results are reported, and tentative conclusions are included.

  7. Sequence-Dependent Persistence Lengths of DNA.

    PubMed

    Mitchell, Jonathan S; Glowacki, Jaroslaw; Grandchamp, Alexandre E; Manning, Robert S; Maddocks, John H

    2017-04-11

    A Monte Carlo code applied to the cgDNA coarse-grain rigid-base model of B-form double-stranded DNA is used to predict a sequence-averaged persistence length of lF = 53.5 nm in the sense of Flory, and of lp = 160 bp or 53.5 nm in the sense of apparent tangent-tangent correlation decay. These estimates are slightly higher than the consensus experimental values of 150 bp or 50 nm, but we believe the agreement to be good given that the cgDNA model is itself parametrized from molecular dynamics simulations of short fragments of length 10-20 bp, with no explicit fit to persistence length. Our Monte Carlo simulations further predict that there can be substantial dependence of persistence lengths on the specific sequence [Formula: see text] of a fragment. We propose, and confirm the numerical accuracy of, a simple factorization that separates the part of the apparent tangent-tangent correlation decay [Formula: see text] attributable to intrinsic shape, from a part [Formula: see text] attributable purely to stiffness, i.e., a sequence-dependent version of what has been called sequence-averaged dynamic persistence length l̅d (=58.8 nm within the cgDNA model). For ensembles of both random and λ-phage fragments, the apparent persistence length [Formula: see text] has a standard deviation of 4 nm over sequence, whereas our dynamic persistence length [Formula: see text] has a standard deviation of only 1 nm. However, there are notable dynamic persistence length outliers, including poly(A) (exceptionally straight and stiff), poly(TA) (tightly coiled and exceptionally soft), and phased A-tract sequence motifs (exceptionally bent and stiff). The results of our numerical simulations agree reasonably well with both molecular dynamics simulation and diverse experimental data including minicircle cyclization rates and stereo cryo-electron microscopy images.

  8. Herbicide Persistence in Seawater Simulation Experiments

    PubMed Central

    Mercurio, Philip; Mueller, Jochen F.; Eaglesham, Geoff; Flores, Florita; Negri, Andrew P.

    2015-01-01

    Herbicides are detected year-round in marine waters, including those of the World Heritage listed Great Barrier Reef (GBR). The few previous studies that have investigated herbicide persistence in seawater generally reported half-lives in the order of months, and several studies were too short to detect significant degradation. Here we investigated the persistence of eight herbicides commonly detected in the GBR or its catchments in standard OECD simulation flask experiments, but with the aim to mimic natural conditions similar to those found on the GBR (i.e., relatively low herbicide concentrations, typical temperatures, light and microbial communities). Very little degradation was recorded over the standard 60 d period (Experiment 1) so a second experiment was extended to 365 d. Half-lives of PSII herbicides ametryn, atrazine, diuron, hexazinone and tebuthiuron were consistently greater than a year, indicating high persistence. The detection of atrazine and diuron metabolites and longer persistence in mercuric chloride-treated seawater confirmed that biodegradation contributed to the breakdown of herbicides. The shortest half-life recorded was 88 d for growth-regulating herbicide 2,4-D at 31°C in the dark, while the fatty acid-inhibitor metolachlor exhibited a minimum half-life of 281 d. The presence of moderate light and elevated temperatures affected the persistence of most of the herbicides; however, the scale and direction of the differences were not predictable and were likely due to changes in microbial community composition. The persistence estimates here represent some of the first appropriate data for application in risk assessments for herbicide exposure in tropical marine systems. The long persistence of herbicides identified in the present study helps explain detection of herbicides in nearshore waters of the GBR year round. Little degradation of these herbicides would be expected during the wet season with runoff and associated flood plumes

  9. Herbicide Persistence in Seawater Simulation Experiments.

    PubMed

    Mercurio, Philip; Mueller, Jochen F; Eaglesham, Geoff; Flores, Florita; Negri, Andrew P

    2015-01-01

    Herbicides are detected year-round in marine waters, including those of the World Heritage listed Great Barrier Reef (GBR). The few previous studies that have investigated herbicide persistence in seawater generally reported half-lives in the order of months, and several studies were too short to detect significant degradation. Here we investigated the persistence of eight herbicides commonly detected in the GBR or its catchments in standard OECD simulation flask experiments, but with the aim to mimic natural conditions similar to those found on the GBR (i.e., relatively low herbicide concentrations, typical temperatures, light and microbial communities). Very little degradation was recorded over the standard 60 d period (Experiment 1) so a second experiment was extended to 365 d. Half-lives of PSII herbicides ametryn, atrazine, diuron, hexazinone and tebuthiuron were consistently greater than a year, indicating high persistence. The detection of atrazine and diuron metabolites and longer persistence in mercuric chloride-treated seawater confirmed that biodegradation contributed to the breakdown of herbicides. The shortest half-life recorded was 88 d for growth-regulating herbicide 2,4-D at 31°C in the dark, while the fatty acid-inhibitor metolachlor exhibited a minimum half-life of 281 d. The presence of moderate light and elevated temperatures affected the persistence of most of the herbicides; however, the scale and direction of the differences were not predictable and were likely due to changes in microbial community composition. The persistence estimates here represent some of the first appropriate data for application in risk assessments for herbicide exposure in tropical marine systems. The long persistence of herbicides identified in the present study helps explain detection of herbicides in nearshore waters of the GBR year round. Little degradation of these herbicides would be expected during the wet season with runoff and associated flood plumes

  10. Prenatal diazepam induced persisting depression of cellular immune responses.

    PubMed

    Schlumpf, M; Ramseier, H; Lichtensteiger, W

    1989-01-01

    Treatment of pregnant Long Evans rats with a low dose of diazepam (1.25 mg/kg per day s.c.) from gestational day (GD) 14 to 20 resulted in severe and long lasting depression of cellular immune responses in male and female offspring. T lymphocyte proliferation, induced by allogeneic stimulation in mixed lymphocyte culture (MLC) or geneic stimulation in mixed lymphocyte culture (MLC) or mitogenic stimulation (concanavalin A), decreased by 50 % or more over a postnatal period of about 2 months. Treatment of the pregnant dam during the early fetal period, from GD 12 to GD 16, did not significantly affect these immune parameters, whereas treatment during later gestation, from GD 16 to 20, significantly affected T lymphocyte function. Clonazepam, a benzodiazepine with high affinity for the central type benzodiazepine site, also affected cellular immune response in offspring. Our data indicate that benzodiazepine treatment during the fetal period may result in persistent postnatal deficiency of cellular immune responses. The relative role of central and peripheral type benzodiazepine receptor and possible interactions with maternal and fetal pituitary - adrenocortical systems are discussed.

  11. Vegetation and Ecological Characteristics of Mixed-Conifer and Red Fir Forests at the Teakettle Experimental Forest

    Treesearch

    Malcolm North; Brian Oakley; Jiquan Chen; Heather Erickson; Andrew Gray; Antonio Izzo; Dale Johnson; Siyan Ma; Jim Marra; Marc Meyer; Kathryn Purcell; Tom Rambo; Dave Rizzo; Brent Roath; Tim. Schowalter

    2002-01-01

    Detailed analysis of mixed-conifer and red fir forests were made from extensive, large vegetation sampling, systematically conducted throughout the Teakettle Experimental Forest. Mixed conifer is characterized by distinct patch conditions of closed-canopy tree clusters, persistent gaps and shrub thickets. This heterogeneous spatial structure provides contrasting...

  12. Environmental unpredictability and inbreeding depression select for mixed dispersal syndromes.

    PubMed

    Hidalgo, Jorge; Casas, Rafael Rubio de; Á Muñoz, Miguel

    2016-04-05

    Mixed dispersal syndromes have historically been regarded as a bet-hedging mechanism that enhances survivorship in unpredictable environments, ensuring that some propagules stay in the maternal environment while others can potentially colonize new sites. However, this entails paying the costs of both dispersal and non-dispersal. Propagules that disperse are likely to encounter unfavorable conditions, while non-dispersing propagules might form inbred populations of close relatives. Here, we investigate the conditions under which mixed dispersal syndromes emerge and are evolutionarily stable, taking into account the risks of both environmental unpredictability and inbreeding. Using mathematical and computational modeling, we show that high dispersal propensity is favored whenever environmental unpredictability is low and inbreeding depression high, whereas mixed dispersal syndromes are adaptive under high environmental unpredictability, more particularly if inbreeding depression is small. Although pure dispersal is frequently adaptive, mixed dispersal represents the optimal strategy under many different parameterizations of our models, indicating that this strategy is likely to be favored in a wide variety of contexts. Furthermore, monomorphic populations go inevitably extinct when environmental and genetic costs are high, whilst mixed strategies can maintain viable populations even under very extreme conditions. Our models support the hypothesis that the interplay between inbreeding depression and environmental unpredictability shapes dispersal syndromes, often resulting in mixed strategies. Moreover, mixed dispersal seems to facilitate persistence whenever conditions are critical or nearly critical for survival.

  13. Mixing efficiency of turbulent patches in stably stratified flows

    NASA Astrophysics Data System (ADS)

    Garanaik, Amrapalli; Venayagamoorthy, Subhas Karan

    2016-11-01

    A key quantity that is essential for estimating the turbulent diapycnal (irreversible) mixing in stably stratified flow is the mixing efficiency Rf*, which is a measure of the amount of turbulent kinetic energy that is irreversibly converted into background potential energy. In particular, there is an ongoing debate in the oceanographic mixing community regarding the utility of the buoyancy Reynolds number (Reb) , particularly with regard to how mixing efficiency and diapycnal diffusivity vary with Reb . Specifically, is there a universal relationship between the intensity of turbulence and the strength of the stratification that supports an unambiguous description of mixing efficiency based on Reb ? The focus of the present study is to investigate the variability of Rf* by considering oceanic turbulence data obtained from microstructure profiles in conjunction with data from laboratory experiments and DNS. Field data analysis has done by identifying turbulent patches using Thorpe sorting method for potential density. The analysis clearly shows that high mixing efficiencies can persist at high buoyancy Reynolds numbers. This is contradiction to previous studies which predict that mixing efficiency should decrease universally for Reb greater than O (100) . Funded by NSF and ONR.

  14. Neurodevelopment for syntactic processing distinguishes childhood stuttering recovery versus persistence.

    PubMed

    Usler, Evan; Weber-Fox, Christine

    2015-01-01

    Characterized by the presence of involuntary speech disfluencies, developmental stuttering is a neurodevelopmental disorder of atypical speech-motor coordination. Although the etiology of stuttering is multifactorial, language development during early childhood may influence both the onset of the disorder and the likelihood of recovery. The purpose of this study was to determine whether differences in neural indices mediating language processing are associated with persistence or recovery in school-age children who stutter. Event-related brain potentials (ERPs) were obtained from 31 6-7-year-olds, including nine children who do not stutter (CWNS), 11 children who had recovered from stuttering (CWS-Rec), and 11 children who persisted in stuttering (CWS-Per), matched for age, and all with similar socioeconomic status, nonverbal intelligence, and language ability. We examined ERPs elicited by semantic and syntactic (phrase structure) violations within an auditory narrative consisting of English and Jabberwocky sentences. In Jabberwocky sentences, content words were replaced with pseudowords to limit semantic context. A mixed effects repeated measures analysis of variance (ANOVA) was computed for ERP components with four within-subject factors, including condition, hemisphere, anterior/posterior distribution, and laterality. During the comprehension of English sentences, ERP activity mediating semantic and syntactic (phrase structure) processing did not distinguish CWS-Per, CWS-Rec, and CWNS. Semantic violations elicited a qualitatively similar N400 component across groups. Phrase structure violations within English sentences also elicited a similar P600 component in all groups. However, identical phrase structure violations within Jabberwocky sentences elicited a P600 in CWNS and CWS-Rec, but an N400-like effect in CWS-Per. The distinguishing neural patterns mediating syntactic, but not semantic, processing provide evidence that specific brain functions for some

  15. Sylgard® Mixing Study

    SciTech Connect

    Bello, Mollie; Welch, Cynthia F.; Goodwin, Lynne Alese; Keller, Jennie

    2014-08-22

    Sylgard® 184 and Sylgard® 186 silicone elastomers form Dow Corning® are used as potting agents across the Nuclear Weapons Complex. A standardized mixing procedure is required for filled versions of these products. The present study is a follow-up to a mixing study performed by MST-7 which established the best mixing procedure to use when adding filler to either 184 or 186 base resins. The most effective and consistent method of mixing resin and curing agent for three modified silicone elastomer recipes is outlined in this report. For each recipe, sample size, mixing type, and mixing time was varied over 10 separate runs. The results show that the THINKY™ Mixer gives reliable mixing over varying batch sizes and mixing times. Hand Mixing can give improved mixing, as indicated by reduced initial viscosity; however, this method is not consistent.

  16. Persistent Photoconductivity in II-VI Mixed Semiconductors Related Critical Phenomena and Applications

    DTIC Science & Technology

    1991-03-31

    VI Semiconductor Thin Films, (3) Comparison Between II-VI and III-V Semiconductors and (4) PCC Transient Behavior . 14. SIWCT TEI S NtIR0PAE I&Pfcu04 I7...excitation photon dose have been measured. Furthermore, the PPC behavior has been investigated under different bias voltage, Vb. We found for the first... behavior in semiconductor thin films since eventually all the novel opto- electronic devices utilizing PPC mechanism will be fabricated from thin films

  17. Radial Mixing in Turbomachines

    DTIC Science & Technology

    1991-03-31

    Belgium March 31, 1991 Final Scientific Report June 1, 1989 - July 31, 1990 VUB -STR -17 Approved for public release; distribution unlimited. - Prepared ...secondary flows and turbulence as sources of mixing was investigated by conducting experiments using hot-wire anemometry and ehtylene tracer gas

  18. Stabilizer for mixed fuels

    SciTech Connect

    Yamamura, M.; Igarashi, T.; Ukigai, T.

    1984-03-13

    A stabilizer for mixed fuels containing a reaction product obtained by reacting (1) a polyol having at least 3 hydroxyl groups in the molecule and a molecular weight of 400-10,000 with (2) an epihalohydrin, as the principal component.

  19. Mixing and Transport.

    ERIC Educational Resources Information Center

    Ditmars, John D.

    1978-01-01

    Presents a literature review of longitudinal dispersion, mixing and transport in streams, rivers, lakes, reservoirs, estuaries, and oceans. This review covers also: (1) fluid-solid mixtures and (2) oil spill behavior. A list of 189 references published in 1976 and 1977 is presented. (HM)

  20. True Anonymity Without Mixes

    NASA Astrophysics Data System (ADS)

    Molina-Jimenez, C.; Marshall, L.

    2002-04-01

    Anonymizers based on mix computers interposed between the sender and the receiver of an e-mail message have been used in the Internet for several years by senders of e-mail messages who do not wish to disclose their identity. Unfortunately, the degree of anonymity provided by this paradigm is limited and fragile. First, the messages sent are not truly anonymous but pseudo-anonymous since one of the mixes, at least, always knows the sender's identity. Secondly, the strength of the system to protect the sender's identity depends on the ability and the willingness of the mixes to keep the secret. If the mixes fail, the sender/'s anonymity is reduced to pieces. In this paper, we propose a novel approach for sending truly anonymous messages over the Internet where the anonymous message is sent from a PDA which uses dynamically assigned temporary, non-personal, random IP and MAC addresses. Anonymous E-cash is used to pay for the service.

  1. Mixed-Initiative Clustering

    ERIC Educational Resources Information Center

    Huang, Yifen

    2010-01-01

    Mixed-initiative clustering is a task where a user and a machine work collaboratively to analyze a large set of documents. We hypothesize that a user and a machine can both learn better clustering models through enriched communication and interactive learning from each other. The first contribution or this thesis is providing a framework of…

  2. Mixed-Initiative Clustering

    ERIC Educational Resources Information Center

    Huang, Yifen

    2010-01-01

    Mixed-initiative clustering is a task where a user and a machine work collaboratively to analyze a large set of documents. We hypothesize that a user and a machine can both learn better clustering models through enriched communication and interactive learning from each other. The first contribution or this thesis is providing a framework of…

  3. Mixing and Transport.

    ERIC Educational Resources Information Center

    Ditmars, John D.

    1978-01-01

    Presents a literature review of longitudinal dispersion, mixing and transport in streams, rivers, lakes, reservoirs, estuaries, and oceans. This review covers also: (1) fluid-solid mixtures and (2) oil spill behavior. A list of 189 references published in 1976 and 1977 is presented. (HM)

  4. Mixed valent metals

    NASA Astrophysics Data System (ADS)

    Riseborough, P. S.; Lawrence, J. M.

    2016-08-01

    We review the theory of mixed-valent metals and make comparison with experiments. A single-impurity description of the mixed-valent state is discussed alongside the description of the nearly-integer valent or Kondo limit. The degeneracy N of the f-shell plays an important role in the description of the low-temperature Fermi-liquid state. In particular, for large N, there is a rapid cross-over between the mixed-valent and the Kondo limit when the number of f electrons is changed. We discuss the limitations on the application of the single-impurity description to concentrated compounds such as those caused by the saturation of the Kondo effect and those due to the presence of magnetic interactions between the impurities. This discussion is followed by a description of a periodic lattice of mixed-valent ions, including the role of the degeneracy N. The article concludes with a comparison of theory and experiment. Topics covered include the single-impurity Anderson model, Luttinger’s theorem, the Friedel sum rule, the Schrieffer-Wolff transformation, the single-impurity Kondo model, Kondo screening, the Wilson ratio, local Fermi-liquids, Fermi-liquid sum rules, the Noziéres exhaustion principle, Doniach’s diagram, the Anderson lattice model, the Slave-Boson method, etc.

  5. Persistent agents in Axelrod's social dynamics model

    NASA Astrophysics Data System (ADS)

    Reia, Sandro M.; Neves, Ubiraci P. C.

    2016-01-01

    Axelrod's model of social dynamics has been studied under the effect of external media. Here we study the formation of cultural domains in the model by introducing persistent agents. These are agents whose cultural traits are not allowed to change but may be spread through local neighborhood. In the absence of persistent agents, the system is known to present a transition from a monocultural to a multicultural regime at some critical Q (number of traits). Our results reveal a dependence of critical Q on the occupation probability p of persistent agents and we obtain the phase diagram of the model in the (p,Q) -plane. The critical locus is explained by the competition of two opposite forces named here barrier and bonding effects. Such forces are verified to be caused by non-persistent agents which adhere (adherent agents) to the set of traits of persistent ones. The adherence (concentration of adherent agents) as a function of p is found to decay for constant Q. Furthermore, adherence as a function of Q is found to decay as a power law with constant p.

  6. Emergence of Persistent Infection due to Heterogeneity

    NASA Astrophysics Data System (ADS)

    Agrawal, Vidit; Moitra, Promit; Sinha, Sudeshna

    2017-02-01

    We explore the emergence of persistent infection in a closed region where the disease progression of the individuals is given by the SIRS model, with an individual becoming infected on contact with another infected individual. We investigate the persistence of contagion qualitatively and quantitatively, under increasing heterogeneity in the partitioning of the population into different disease compartments, as well as increasing heterogeneity in the phases of the disease among individuals within a compartment. We observe that when the initial population is uniform, consisting of individuals at the same stage of disease progression, infection arising from a contagious seed does not persist. However when the initial population consists of randomly distributed refractory and susceptible individuals, a single source of infection can lead to sustained infection in the population, as heterogeneity facilitates the de-synchronization of the phases in the disease cycle of the individuals. We also show how the average size of the window of persistence of infection depends on the degree of heterogeneity in the initial composition of the population. In particular, we show that the infection eventually dies out when the entire initial population is susceptible, while even a few susceptibles among an heterogeneous refractory population gives rise to a large persistent infected set.

  7. Emergence of Persistent Infection due to Heterogeneity.

    PubMed

    Agrawal, Vidit; Moitra, Promit; Sinha, Sudeshna

    2017-02-01

    We explore the emergence of persistent infection in a closed region where the disease progression of the individuals is given by the SIRS model, with an individual becoming infected on contact with another infected individual. We investigate the persistence of contagion qualitatively and quantitatively, under increasing heterogeneity in the partitioning of the population into different disease compartments, as well as increasing heterogeneity in the phases of the disease among individuals within a compartment. We observe that when the initial population is uniform, consisting of individuals at the same stage of disease progression, infection arising from a contagious seed does not persist. However when the initial population consists of randomly distributed refractory and susceptible individuals, a single source of infection can lead to sustained infection in the population, as heterogeneity facilitates the de-synchronization of the phases in the disease cycle of the individuals. We also show how the average size of the window of persistence of infection depends on the degree of heterogeneity in the initial composition of the population. In particular, we show that the infection eventually dies out when the entire initial population is susceptible, while even a few susceptibles among an heterogeneous refractory population gives rise to a large persistent infected set.

  8. Breastfeeding may protect against persistent stuttering.

    PubMed

    Mahurin-Smith, Jamie; Ambrose, Nicoline G

    2013-01-01

    This study investigated the hypothesis that breastfeeding in infancy might protect against persistent stuttering in children. We collected new data from the mothers of current and past participants in the Illinois Stuttering Research Program on their children's feeding history during infancy. We obtained 47 usable responses, for 17 children with persistent stuttering and 30 children who recovered naturally after a period of stuttering. A chi-squared test for linear trend revealed a significant relationship between breastfeeding duration and the likelihood of natural recovery for the boys in the sample. Mothers of children in the persistent group were no more likely to report early feeding difficulties which might have suggested an underlying oral motor deficit in children predisposed toward persistent stuttering. Our results offer preliminary support for the idea that breastfeeding may confer a measure of protection against persistent stuttering. The fatty acid profile of human milk, with its potential to affect both gene expression and the composition of neural tissue, may explain this association. Further research is called for. The reader will be able to discuss at least one reason why human milk may make a difference in neurodevelopment generally and with regard to stuttering outcomes specifically. Additionally, the reader will be able to describe the relationship between breastfeeding duration and stuttering recovery observed in this sample. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Emergence of Persistent Infection due to Heterogeneity

    PubMed Central

    Agrawal, Vidit; Moitra, Promit; Sinha, Sudeshna

    2017-01-01

    We explore the emergence of persistent infection in a closed region where the disease progression of the individuals is given by the SIRS model, with an individual becoming infected on contact with another infected individual. We investigate the persistence of contagion qualitatively and quantitatively, under increasing heterogeneity in the partitioning of the population into different disease compartments, as well as increasing heterogeneity in the phases of the disease among individuals within a compartment. We observe that when the initial population is uniform, consisting of individuals at the same stage of disease progression, infection arising from a contagious seed does not persist. However when the initial population consists of randomly distributed refractory and susceptible individuals, a single source of infection can lead to sustained infection in the population, as heterogeneity facilitates the de-synchronization of the phases in the disease cycle of the individuals. We also show how the average size of the window of persistence of infection depends on the degree of heterogeneity in the initial composition of the population. In particular, we show that the infection eventually dies out when the entire initial population is susceptible, while even a few susceptibles among an heterogeneous refractory population gives rise to a large persistent infected set. PMID:28145522

  10. A test to identify persistent picky eaters.

    PubMed

    Toyama, Hannah; Agras, W Stewart

    2016-12-01

    Picky eating is common and usually relatively brief as new foods are accepted. Persistent picky eating, however, is often associated with comorbid psychopathology. The aim of this study was to use parent-reported child feeding behaviors to identify which picky eaters persist. Participants were a subsample from the Stanford Infant Growth Study a prospective study of child development. Out of the 216 infants, 86 were identified as picky eaters. Picky eaters were separated into two groups using a median split: short-term (n=40) and persistent picky eaters (n=46). Recursive Partitioning detected three significant parent-reported feeding questions that may identify persistent picky eaters at an early age: Is your child a picky eater? (yes), does s/he have strong likes with regard to food (yes), does your child accept new foods readily? (no). These results provide a first step allowing providers to identify persistent picky eaters and possibly enable intervention at an early age. Further studies are needed to replicate and extend these findings in another sample of picky eaters. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Calmodulin limits pathogenic Na+ channel persistent current

    PubMed Central

    Yan, Haidun; Wang, Chaojian; Marx, Steven O.

    2017-01-01

    Increased “persistent” current, caused by delayed inactivation, through voltage-gated Na+ (NaV) channels leads to cardiac arrhythmias or epilepsy. The underlying molecular contributors to these inactivation defects are poorly understood. Here, we show that calmodulin (CaM) binding to multiple sites within NaV channel intracellular C-terminal domains (CTDs) limits persistent Na+ current and accelerates inactivation across the NaV family. Arrhythmia or epilepsy mutations located in NaV1.5 or NaV1.2 channel CTDs, respectively, reduce CaM binding either directly or by interfering with CTD–CTD interchannel interactions. Boosting the availability of CaM, thus shifting its binding equilibrium, restores wild-type (WT)–like inactivation in mutant NaV1.5 and NaV1.2 channels and likewise diminishes the comparatively large persistent Na+ current through WT NaV1.6, whose CTD displays relatively low CaM affinity. In cerebellar Purkinje neurons, in which NaV1.6 promotes a large physiological persistent Na+ current, increased CaM diminishes the persistent Na+ current, suggesting that the endogenous, comparatively weak affinity of NaV1.6 for apoCaM is important for physiological persistent current. PMID:28087622

  12. Persistence of community college engineering science students: The impact of selected cognitive and noncognitive characteristics

    NASA Astrophysics Data System (ADS)

    Chatman, Lawrence M., Jr.

    If the United States is to remain technologically competitive, persistence in engineering programs must improve. This study on student persistence employed a mixed-method design to identify the cognitive and noncognitive factors which contribute to students remaining in an engineering science curriculum or switching from an engineering curriculum at a community college in the northeast United States. Records from 372 students were evaluated to determine the characteristics of two groups: those students that persisted with the engineering curriculum and those that switched from engineering; also, the dropout phenomenon was evaluated. The quantitative portion of the study used a logistic regression analyses on 22 independent variables, while the qualitative portion of the study used group interviews to investigate the noncognitive factors that influenced persisting or switching. The qualitative portion of the study added depth and credibility to the results from the quantitative portion. The study revealed that (1) high grades in first year calculus, physics and chemistry courses, (2) fewer number of semesters enrolled, (3) attendance with full time status, and (4) not participating in an English as a Second Language (ESL) program were significant variables used to predict student persistence. The group interviews confirmed several of these contributing factors. Students that dropped out of college began with (1) the lowest levels of remediation, (2) the lowest grade point averages, and (3) the fewest credits earned.

  13. Vegetation persistence and carbon storage: Implications for environmental water management for Phragmites australis

    NASA Astrophysics Data System (ADS)

    Whitaker, Kai; Rogers, Kerrylee; Saintilan, Neil; Mazumder, Debashish; Wen, Li; Morrison, R. J.

    2015-07-01

    Environmental water allocations are used to improve the ecological health of wetlands. There is now increasing demand for allocations to improve ecosystem productivity and respiration, and enhance carbon sequestration. Despite global recognition of wetlands as carbon sinks, information regarding carbon dynamics is lacking. This is the first study estimating carbon sequestration for semiarid Phragmites australis reedbeds. The study combined aboveground biomass assessments with stable isotope analyses of soils and modeling of biomass using Normalized Digital Vegetation Index (NDVI) to investigate the capacity of environmental water allocations to improve carbon storage. The study considered relationships between soil organic carbon (SOC), carbon sources, and reedbed persistence in the Macquarie Marshes, a regulated semiarid floodplain of the Murray-Darling Basin, Australia. SOC storage levels to 1 m soil depth were higher in persistent reedbeds (167 Mg ha-1) than ephemeral reedbeds (116-138 Mg ha-1). In situ P. australis was the predominant source of surface SOC at persistent reedbeds; mixed sources of surface SOC were proposed for ephemeral reedbeds. 13C enrichment with increasing soil depth occurred in persistent and ephemeral reedbeds and may not relate to flow characteristics. Despite high SOC at persistent reedbeds, differences in the rate of accretion contributed to significantly higher rates of carbon sequestration at ephemeral reedbeds (approximately 554 and 465 g m-2 yr-1) compared to persistent reedbeds (5.17 g m-2 yr-1). However, under current water regimes, rapid accretion at ephemeral reedbeds cannot be maintained. Effective management of persistent P. australis reedbeds may enhance carbon sequestration in the Macquarie Marshes and floodplain wetlands more generally.

  14. Persistent toxic substances: sources, fates and effects.

    PubMed

    Wong, Ming H; Armour, Margaret-Ann; Naidu, Ravi; Man, Ming

    2012-01-01

    Persistent toxic substances (PTS) include the Stockholm persistent organic pollutants, like dichlorodiphenyltrichloroethane, polychlorinated biphenyls, dioxin/furan, etc., and organometallic compounds, like organomercury, organotin, and organolead, which all share the same characteristics of being persistent, toxic, bioaccumulative, and able to travel long distances through different media. The adverse health effects of some of the emerging chemicals like pentabromodiphenyl ether, bisphenol A, and di(2-ethylhexyl)phthalate, which are widely used in daily appliances (e.g., TVs, computers, mobile phones, plastic baby bottles), have become a public health concern due to more evidence now available showing their adverse effects like disturbance of the endocrine system and cancer. This article is an attempt to review the current status of PTS in our environment, citing case studies in China and North America, and whether our existing drinking water treatment and wastewater treatment processes are adequate in removing them from water. Some management issues of these emerging chemicals of concern are also discussed.

  15. Persistence and predictability in a perfect model

    NASA Technical Reports Server (NTRS)

    Schubert, Siegfried D.; Suarez, Max J.; Schemm, Jae-Kyung

    1992-01-01

    A realistic two-level GCM is used to examine the relationship between predictability and persistence. Predictability is measured by the average divergence of ensembles of solutions starting from perturbed initial conditions, and persistence is defined in terms of the autocorrelation function based on a single long-term model integration. The average skill of the dynamical forecasts is compared with the skill of simple persistence-based statistical forecasts. For initial errors comparable in magnitude to present-day analysis errors, the statistical forecast loses all skill after about one week, reflecting the lifetime of the lowest frequency fluctuations in the model. Large ensemble mean dynamical forecasts would be expected to remain skillful for about 3 wk. The disparity between the skill of the statistical and dynamical forecasts is greater for the higher frequency modes, which have little memory beyond 1 d, yet remain predictable for about 2 wk. The results are analyzed in terms of two characteristic time scales.

  16. Improving Underrepresented Minority Student Persistence in STEM.

    PubMed

    Estrada, Mica; Burnett, Myra; Campbell, Andrew G; Campbell, Patricia B; Denetclaw, Wilfred F; Gutiérrez, Carlos G; Hurtado, Sylvia; John, Gilbert H; Matsui, John; McGee, Richard; Okpodu, Camellia Moses; Robinson, T Joan; Summers, Michael F; Werner-Washburne, Maggie; Zavala, MariaElena

    2016-01-01

    Members of the Joint Working Group on Improving Underrepresented Minorities (URMs) Persistence in Science, Technology, Engineering, and Mathematics (STEM)-convened by the National Institute of General Medical Sciences and the Howard Hughes Medical Institute-review current data and propose deliberation about why the academic "pathways" leak more for URM than white or Asian STEM students. They suggest expanding to include a stronger focus on the institutional barriers that need to be removed and the types of interventions that "lift" students' interests, commitment, and ability to persist in STEM fields. Using Kurt Lewin's planned approach to change, the committee describes five recommendations to increase URM persistence in STEM at the undergraduate level. These recommendations capitalize on known successes, recognize the need for accountability, and are framed to facilitate greater progress in the future. The impact of these recommendations rests upon enacting the first recommendation: to track successes and failures at the institutional level and collect data that help explain the existing trends.

  17. Persistent Structures in the Turbulent Boundary Layer

    NASA Technical Reports Server (NTRS)

    Palumbo, Dan; Chabalko, Chris

    2005-01-01

    Persistent structures in the turbulent boundary layer are located and analyzed. The data are taken from flight experiments on large commercial aircraft. An interval correlation technique is introduced which is able to locate the structures. The Morlet continuous wavelet is shown to not only locates persistent structures but has the added benefit that the pressure data are decomposed in time and frequency. To better understand how power is apportioned among these structures, a discrete Coiflet wavelet is used to decompose the pressure data into orthogonal frequency bands. Results indicate that some structures persist a great deal longer in the TBL than would be expected. These structure contain significant power and may be a primary source of vibration energy in the airframe.

  18. The economics associated with persistent pain.

    PubMed

    Phillips, Ceri J; Harper, Christie

    2011-06-01

    This review aims to assess the economic impact of inadequate, inappropriate and ineffective treatments of persistent pain from the perspective of the individual, their families and communities, healthcare systems, economies and societies in general. The economic impact of persistent and chronic pain poses a substantial burden on individual patients, their families, employers, economies and societies in general. It is recognized that the impact of persistent pain is greater than most other health conditions, due to its effects on rates of absenteeism, reduced levels of productivity and increased risk of leaving the labour market, as well as the costs to the healthcare system and other government agencies. The burden of suffering that pain imposes on individuals and the enormous costs that society has to bear as a result clearly demonstrate that policy makers at governmental level and commissioners, and healthcare decision-makers alike should adopt a broad, strategic and coherent perspective in determining issues relating to service provision and resource allocation.

  19. Persistence and predictability in a perfect model

    NASA Technical Reports Server (NTRS)

    Schubert, Siegfried D.; Suarez, Max J.; Schemm, Jae-Kyung

    1992-01-01

    A realistic two-level GCM is used to examine the relationship between predictability and persistence. Predictability is measured by the average divergence of ensembles of solutions starting from perturbed initial conditions, and persistence is defined in terms of the autocorrelation function based on a single long-term model integration. The average skill of the dynamical forecasts is compared with the skill of simple persistence-based statistical forecasts. For initial errors comparable in magnitude to present-day analysis errors, the statistical forecast loses all skill after about one week, reflecting the lifetime of the lowest frequency fluctuations in the model. Large ensemble mean dynamical forecasts would be expected to remain skillful for about 3 wk. The disparity between the skill of the statistical and dynamical forecasts is greater for the higher frequency modes, which have little memory beyond 1 d, yet remain predictable for about 2 wk. The results are analyzed in terms of two characteristic time scales.

  20. The origins of lactase persistence in Europe.

    PubMed

    Itan, Yuval; Powell, Adam; Beaumont, Mark A; Burger, Joachim; Thomas, Mark G

    2009-08-01

    Lactase persistence (LP) is common among people of European ancestry, but with the exception of some African, Middle Eastern and southern Asian groups, is rare or absent elsewhere in the world. Lactase gene haplotype conservation around a polymorphism strongly associated with LP in Europeans (-13,910 C/T) indicates that the derived allele is recent in origin and has been subject to strong positive selection. Furthermore, ancient DNA work has shown that the--13,910*T (derived) allele was very rare or absent in early Neolithic central Europeans. It is unlikely that LP would provide a selective advantage without a supply of fresh milk, and this has lead to a gene-culture coevolutionary model where lactase persistence is only favoured in cultures practicing dairying, and dairying is more favoured in lactase persistent populations. We have developed a flexible demic computer simulation model to explore the spread of lactase persistence, dairying, other subsistence practices and unlinked genetic markers in Europe and western Asia's geographic space. Using data on--13,910*T allele frequency and farming arrival dates across Europe, and approximate Bayesian computation to estimate parameters of interest, we infer that the--13,910*T allele first underwent selection among dairying farmers around 7,500 years ago in a region between the central Balkans and central Europe, possibly in association with the dissemination of the Neolithic Linearbandkeramik culture over Central Europe. Furthermore, our results suggest that natural selection favouring a lactase persistence allele was not higher in northern latitudes through an increased requirement for dietary vitamin D. Our results provide a coherent and spatially explicit picture of the coevolution of lactase persistence and dairying in Europe.

  1. The Origins of Lactase Persistence in Europe

    PubMed Central

    Itan, Yuval; Powell, Adam; Beaumont, Mark A.; Burger, Joachim; Thomas, Mark G.

    2009-01-01

    Lactase persistence (LP) is common among people of European ancestry, but with the exception of some African, Middle Eastern and southern Asian groups, is rare or absent elsewhere in the world. Lactase gene haplotype conservation around a polymorphism strongly associated with LP in Europeans (−13,910 C/T) indicates that the derived allele is recent in origin and has been subject to strong positive selection. Furthermore, ancient DNA work has shown that the −13,910*T (derived) allele was very rare or absent in early Neolithic central Europeans. It is unlikely that LP would provide a selective advantage without a supply of fresh milk, and this has lead to a gene-culture coevolutionary model where lactase persistence is only favoured in cultures practicing dairying, and dairying is more favoured in lactase persistent populations. We have developed a flexible demic computer simulation model to explore the spread of lactase persistence, dairying, other subsistence practices and unlinked genetic markers in Europe and western Asia's geographic space. Using data on −13,910*T allele frequency and farming arrival dates across Europe, and approximate Bayesian computation to estimate parameters of interest, we infer that the −13,910*T allele first underwent selection among dairying farmers around 7,500 years ago in a region between the central Balkans and central Europe, possibly in association with the dissemination of the Neolithic Linearbandkeramik culture over Central Europe. Furthermore, our results suggest that natural selection favouring a lactase persistence allele was not higher in northern latitudes through an increased requirement for dietary vitamin D. Our results provide a coherent and spatially explicit picture of the coevolution of lactase persistence and dairying in Europe. PMID:19714206

  2. Gender and race/ethnic differences in the persistence of alcohol, drug, and poly-substance use disorders.

    PubMed

    Evans, Elizabeth A; Grella, Christine E; Washington, Donna L; Upchurch, Dawn M

    2017-05-01

    To examine gender and racial/ethnic differences in the effect of substance use disorder (SUD) type on SUD persistence. Data were provided by 1025 women and 1835 men from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) to examine whether gender and race/ethnicity (Non-Hispanic White, Black, Hispanic) moderate the effects of DSM-IV defined past-12 month SUD type (alcohol, drug, poly-substance) on SUD persistence at 3-year follow-up, controlling for covariates. Using gender-stratified weighted binary logistic regression, we examined predictors of SUD persistence, tested an SUD type by race/ethnicity interaction term, and calculated and conducted Bonferroni corrected pairwise comparisons of predicted probabilities. SUD persistence rates at 3-year follow-up differed for SUD type by gender by race/ethnicity sub-group, and ranged from 31% to 81%. SUD persistence rates were consistently higher among poly-substance users; patterns were mixed in relation to gender and race/ethnicity. Among women, alcohol disordered Hispanics were less likely to persist than Whites. Among men, drug disordered Hispanics were less likely to persist than Whites. Also, Black men with an alcohol or drug use disorder were less likely to persist than Whites, but Black men with a poly-substance use disorder were more likely to persist than Hispanics. The effect of SUD type on SUD persistence varies by race/ethnicity, and the nature of these relationships is different by gender. Such knowledge could inform tailoring of SUD screening and treatment programs, potentially increasing their impact. Published by Elsevier B.V.

  3. Screening chemicals for persistence in the environment

    SciTech Connect

    Gouin, T.; MacKay, D.; Webster, E.; Wania, F.

    2000-03-01

    A method is suggested for rapid screening of chemicals for persistence in the environment. Physical-chemical equilibrium partitioning information between air, water, and octanol are used as a first screen to identify the media for which degradation half-lives are required and those for which half-lives may be unnecessary. An overall persistence under equilibrium conditions is then estimated using half-lives in air, water, soil, and sediment using a steady-state mass balance model. A graphical technique to identify the key half-lives is demonstrated using 233 chemicals. For chemicals of more extreme partitioning properties, some half-lives may not be needed.

  4. Three-dimensional diffusion with helical persistence

    NASA Astrophysics Data System (ADS)

    Larralde, Hernán; Leyvraz, François

    2015-07-01

    We formulate the the problem of persistent diffusion in three dimensions from the perspective of the Frenet-Serret equations. In contrast to one and two-dimensional systems, in three-dimensions persistent diffusion is, in general, a third order process. In this paper we derive a Fokker-Planck equation for the process and we calculate its effective diffusion constant. We also provide expressions for the asymptotic average displacement of the walk, as well as explicit expressions for the Fourier-Laplace transform of the correlations between the tangent, normal and binormal vectors of the motion.

  5. Chronic Bacterial Pathogens: Mechanisms of Persistence

    PubMed Central

    Byndloss, Mariana X.; Tsolis, Renee M

    2015-01-01

    Summary Many bacterial pathogens can cause acute infections that are cleared with onset of adaptive immunity, however a subset of these pathogens can establish persistent, and sometimes lifelong infections. While bacteria causing chronic infections are phylogenetically diverse, they share common features in their interactions with the host that enable a protracted period of colonization. This chapter will compare the persistence strategies of two chronic pathogens from the Proteobacteria, Brucella abortus, and Salmonella enterica serovar Typhi (S. Typhi) to consider how these two pathogens, which are very different at the genomic level, can utilize common strategies to evade immune clearance to cause chronic intracellular infections of the mononuclear phagocyte system. PMID:27227304

  6. Heterologous Immunity and Persistent Murine Cytomegalovirus Infection

    PubMed Central

    Che, Jenny W.; Daniels, Keith A.; Selin, Liisa K.

    2016-01-01

    ABSTRACT One's history of infections can affect the immune response to unrelated pathogens and influence disease outcome through the process of heterologous immunity. This can occur after acute viral infections, such as infections with lymphocytic choriomeningitis virus (LCMV) and vaccinia virus, where the pathogens are cleared, but it becomes a more complex issue in the context of persistent infections. In this study, murine cytomegalovirus (MCMV) was used as a persistent infection model to study heterologous immunity with LCMV. If mice were previously immune to LCMV and then infected with MCMV (LCMV+MCMV), they had more severe immunopathology, enhanced viral burden in multiple organs, and suppression of MCMV-specific T cell memory inflation. MCMV infection initially reduced the numbers of LCMV-specific memory T cells, but continued MCMV persistence did not further erode memory T cells specific to LCMV. When MCMV infection was given first (MCMV+LCMV), the magnitude of the acute T cell response to LCMV declined with age though this age-dependent decline was not dependent on MCMV. However, some of these MCMV persistently infected mice with acute LCMV infection (7 of 36) developed a robust immunodominant CD8 T cell response apparently cross-reactive between a newly defined putative MCMV epitope sequence, M57727–734, and the normally subdominant LCMV epitope L2062–2069, indicating a profound private specificity effect in heterologous immunity between these two viruses. These results further illustrate how a history of an acute or a persistent virus infection can substantially influence the immune responses and immune pathology associated with acute or persistent infections with an unrelated virus. IMPORTANCE This study extends our understanding of heterologous immunity in the context of persistent viral infection. The phenomenon has been studied mostly with viruses such as LCMV that are cleared, but the situation can be more complex with a persistent virus such as

  7. Long persistence effects of geomagnetic activity

    NASA Astrophysics Data System (ADS)

    Wrenn, Gordon L.

    1990-03-01

    The identification of the physical processes which perturb the dynamic equilibrium of the charged particle populations in the terrestrial magnetosphere is investigated. A planetary index was used and it was proved that the introduction of a persistence factor for a derived index, a time weighted accumulation of recent values, gives a better correlation with an estimation of characteristic persistence times in order to establish the temporal response of observed effects in relation to available measures of geomagnetic activity. The analysis procedure was illustrated by results pertaining to ionospheric foF2, cold plasma concentration at geosynchronous orbit and ring current strength.

  8. Amnestically Induced Persistence in Random Walks

    NASA Astrophysics Data System (ADS)

    Cressoni, J. C.; da Silva, Marco Antonio Alves; Viswanathan, G. M.

    2007-02-01

    We study how the Hurst exponent α depends on the fraction f of the total time t remembered by non-Markovian random walkers that recall only the distant past. We find that otherwise nonpersistent random walkers switch to persistent behavior when inflicted with significant memory loss. Such memory losses induce the probability density function of the walker’s position to undergo a transition from Gaussian to non-Gaussian. We interpret these findings of persistence in terms of a breakdown of self-regulation mechanisms and discuss their possible relevance to some of the burdensome behavioral and psychological symptoms of Alzheimer’s disease and other dementias.

  9. Persistent and refractory thrush with unknown cause.

    PubMed

    Wang, Lili; Liu, Dongjuan; Zhao, Xin; Wu, Lanyan; Zhou, Yu; Chen, Qianming; Zeng, Xin; Jin, Xin

    2015-03-01

    Oral thrush is considered as the opportunistic infection, which is caused by fungus Candida albicans. Various kinds of immunodeficiency diseases, such as HIV infection, immunosuppressive therapy, use of broad-spectrum antibiotics, and invasive surgical procedures such as solid organ or bone marrow transplantation, lead to increased susceptibility to fungal infections, but persistent and refractory thrush, with typical clinical signs of oral fungal infection and without any other sign of immunodeficiencies, has not been reported so far. We describe a case of persistent and refractory thrush with Klinefelter syndrome (47, XXY) as the unusual cause.

  10. Platforms for Persistent Communications, Surveillance and Reconnaissance

    DTIC Science & Technology

    2008-09-01

    GPS Geosynchronous Orbit (GEO) – e.g.,DSCS/ UFO / INMARSAT Grading Factors (1–4 shown as colors) Sensitivity Analysis Observations Notes: 10Persistent...SWaP/Manpack Not Voice Capable Voice Capable Image Capable Video Capable Acquisition Cost > $50M $10M – $50M $1M – $10M < $1M Flying Hr Cost > $20K $5K...GPS Geosynchronous Orbit (GEO) – e.g.,DSCS/ UFO / INMARSAT Grading Factors (1–4 shown as colors) Sensitivity Analysis Observations Notes: 12Persistent

  11. EEG findings in the persistent vegetative state.

    PubMed

    Kulkarni, Vidya P; Lin, Kaiwen; Benbadis, Selim R

    2007-12-01

    The definition of the persistent vegetative state (PVS) is relatively straightforward, but its diagnosis can be challenging. We reviewed a series of EEG performed in patients with PVS to assess the diagnostic value of EEG. We reviewed records of all hospital patients with a diagnosis of persistent vegetative PVS. EEG findings included normal, continuous generalized slowing, intermittent generalized slowing, background slowing, background suppression, alpha, generalized periodic pattern, PLEDS, and triphasic waves. EEG findings had no association with etiology and varied from one pattern to another in the same patients' EEGs obtained at different times (see table). We conclude that EEG findings in PVS are heterogeneous and too variable to be of diagnostic value.

  12. Amnestically induced persistence in random walks.

    PubMed

    Cressoni, J C; da Silva, Marco Antonio Alves; Viswanathan, G M

    2007-02-16

    We study how the Hurst exponent alpha depends on the fraction f of the total time t remembered by non-Markovian random walkers that recall only the distant past. We find that otherwise nonpersistent random walkers switch to persistent behavior when inflicted with significant memory loss. Such memory losses induce the probability density function of the walker's position to undergo a transition from Gaussian to non-Gaussian. We interpret these findings of persistence in terms of a breakdown of self-regulation mechanisms and discuss their possible relevance to some of the burdensome behavioral and psychological symptoms of Alzheimer's disease and other dementias.

  13. Association Between Persistent Pain and Memory Decline and Dementia in a Longitudinal Cohort of Elders.

    PubMed

    Whitlock, Elizabeth L; Diaz-Ramirez, L Grisell; Glymour, M Maria; Boscardin, W John; Covinsky, Kenneth E; Smith, Alexander K

    2017-08-01

    Chronic pain is common among the elderly and is associated with cognitive deficits in cross-sectional studies; the population-level association between chronic pain and longitudinal cognition is unknown. To determine the population-level association between persistent pain, which may reflect chronic pain, and subsequent cognitive decline. Cohort study with biennial interviews of 10 065 community-dwelling older adults in the nationally representative Health and Retirement Study who were 62 years or older in 2000 and answered pain and cognition questions in both 1998 and 2000. Data analysis was conducted between June 24 and October 31, 2016. "Persistent pain," defined as a participant reporting that he or she was often troubled with moderate or severe pain in both the 1998 and 2000 interviews. Coprimary outcomes were composite memory score and dementia probability, estimated by combining neuropsychological test results and informant and proxy interviews, which were tracked from 2000 through 2012. Linear mixed-effects models, with random slope and intercept for each participant, were used to estimate the association of persistent pain with slope of the subsequent cognitive trajectory, adjusting for demographic characteristics and comorbidities measures in 2000 and applying sampling weights to represent the 2000 US population. We hypothesized that persistent pain would predict accelerated memory decline and increased probability of dementia. To quantify the impact of persistent pain on functional independence, we combined our primary results with information on the association between memory and ability to manage medications and finances independently. Of the 10 065 eligible HRS sample members, 60% were female, and median baseline age was 73 years (interquartile range, 67-78 years). At baseline, persistent pain affected 10.9% of participants and was associated with worse depressive symptoms and more limitations in activities of daily living. After covariate

  14. Supersonic jet mixing enhancement by vortex generators

    NASA Technical Reports Server (NTRS)

    Samimy, M.; Reeder, M. F.; Zaman, K. B. M. Q.

    1991-01-01

    Experiments were conducted to explore the effects of vortex generators, in the form of tabs projecting normally into the jet, on the mixing and the far-field noise characteristics of a jet. A converging-diverging nozzle with a design Mach number of 1.36 was used in the experiments. The flow regimes from subsonic to highly underexpanded supersonic conditions were studied. One, two, and four tabs were used and some of the findings of previous investigators were examined and confirmed. The tabs eliminated screech noise from moderately overexpanded cases to highly underexpanded cases. Detailed flow visualizations and measurements showed that two tabs bifurcated the jet at all Mach numbers. While the effect of two tabs was persistent and the jet remained bifurcated, the distortions produced by one and four tabs disappeared by a streamwise distance of approximately 16 jet diameters. Two and four tabs significantly increased the entrainment of ambient air into the jet.

  15. Using Benchmarking To Strengthen the Assessment of Persistence.

    PubMed

    McLachlan, Michael S; Zou, Hongyan; Gouin, Todd

    2017-01-03

    Chemical persistence is a key property for assessing chemical risk and chemical hazard. Current methods for evaluating persistence are based on laboratory tests. The relationship between the laboratory based estimates and persistence in the environment is often unclear, in which case the current methods for evaluating persistence can be questioned. Chemical benchmarking opens new possibilities to measure persistence in the field. In this paper we explore how the benchmarking approach can be applied in both the laboratory and the field to deepen our understanding of chemical persistence in the environment and create a firmer scientific basis for laboratory to field extrapolation of persistence test results.

  16. Experiments in mixed reality

    NASA Astrophysics Data System (ADS)

    Krum, David M.; Sadek, Ramy; Kohli, Luv; Olson, Logan; Bolas, Mark

    2010-01-01

    As part of the Institute for Creative Technologies and the School of Cinematic Arts at the University of Southern California, the Mixed Reality lab develops technologies and techniques for presenting realistic immersive training experiences. Such experiences typically place users within a complex ecology of social actors, physical objects, and collections of intents, motivations, relationships, and other psychological constructs. Currently, it remains infeasible to completely synthesize the interactivity and sensory signatures of such ecologies. For this reason, the lab advocates mixed reality methods for training and conducts experiments exploring such methods. Currently, the lab focuses on understanding and exploiting the elasticity of human perception with respect to representational differences between real and virtual environments. This paper presents an overview of three projects: techniques for redirected walking, displays for the representation of virtual humans, and audio processing to increase stress.

  17. Mixing by individual swimmers

    NASA Astrophysics Data System (ADS)

    Pushkin, Dmitri; Shum, Henry; Yeomans, Julia

    2012-11-01

    Despite their evolutionary and technological importance, different biomixing mechanisms, their effectiveness and universality remain poorly understood. In this talk we focus on the Lagrangian transport of the surrounding fluid by swimmers. Low Re passive tracers advected by swimmers move in loops that are, in general, almost closed. We analyze the reasons for this behavior and, as non-closedness of the loops is a natural requirement for an efficient mixing, propose a classification of possible mechanisms for biogenic mixing. Next, we discuss the universal (common to all swimmers) and the swimmer-dependent features of the resulting tracer displacements and analyze the Darwin drift, the total fluid volume displaced by a swimmer passing from and to infinity. We show that the Darwin drift is finite for force-free swimmers and can be decomposed into a universal and a swimmer-dependent part. We illustrate our consideration with examples for model swimmers and biological data.

  18. Nozzle mixing apparatus

    SciTech Connect

    Mensink, D.L.

    1992-12-31

    This invention is comprised of a nozzle device for causing two fluids to mix together. In particular, a spray nozzle comprise two hollow, concentric housings, an inner housing and an outer housing. The inner housing has a channel formed therethrough for a first fluid. Its outer surface cooperates with the interior surface of the outer housing to define the second channel for a second fluid. The outer surface of the inner housing and the inner surface of the outer housing each carry a plurality of vanes that interleave but do not touch, each vane of one housing being between two vanes of the other housing. The vanes are curved and the inner surface of the outer housing and the outer surface of the inner housing converge to narrow the second channel. The shape of second channel results in a swirling, accelerating second fluid that will impact the first fluid just past the end of the nozzle where mixing will take place.

  19. Neutrino-Modulino Mixing

    SciTech Connect

    Benakli, K.; Smirnov, A.Y.

    1997-12-01

    We suggest an existence of light singlet fermion, S, which interacts with observable matter only via Planck mass suppressed interaction: {approximately}m{sub 3/2}/M{sub P}, where m{sub 3/2} is the supergravity gravitino mass. If the mass of the singlet equals {approximately}m{sup 2}{sub 3/2}/M{sub P}, then {nu}{sub e}{r_arrow}S resonance conversion solves the solar neutrino problem or leads to observable effects. The {nu}S mixing changes supernova neutrino fluxes and has an impact on the primordial nucleosynthesis. The singlet S can originate as the supersymmetric partner of the moduli fields in supergravity or low energy effective theory stemming from superstrings. The {nu}S mixing may be accompanied by observable R-parity breaking effects. {copyright} {ital 1997} {ital The American Physical Society}

  20. Magnetically driven surface mixing

    NASA Astrophysics Data System (ADS)

    Belkin, M.; Snezhko, A.; Aranson, I. S.; Kwok, W.-K.

    2009-07-01

    Magnetic microparticles suspended on the surface of liquid and energized by vertical alternating magnetic field exhibit complex collective behavior. Various immobile and self-propelled self-assembled structures have been observed. Here, we report on experimental studies of mixing and surface diffusion processes in this system. We show that the pattern-induced surface flows have properties of quasi-two-dimensional turbulence. Correspondingly, the surface advection of tracer particle exhibits properties of Brownian diffusion.