Science.gov

Sample records for post polycythemic myelofibrosis

  1. INC424 for Patients With Myelofibrosis, Post Polycythemia Myelofibrosis or Post-essential Thrombocythemia Myelofibrosis

    ClinicalTrials.gov

    2016-11-27

    Myelofibrosis (PMF); Post Polycythemia Myelofibrosis (PPV MF); Post-essential Thrombocythemia Myelofibrosis (PET-MF); Myelofibrosis; Post Polycythemia Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis

  2. Myelofibrosis

    MedlinePlus

    ... metaplasia; Agnogenic myeloid metaplasia; Primary myelofibrosis; Secondary myelofibrosis; Bone marrow - myelofibrosis ... Bone marrow is the soft, fatty tissue inside your bones. Stem cells are immature cells in the bone ...

  3. Myelofibrosis

    MedlinePlus

    ... is an uncommon type of chronic leukemia — a cancer that affects the blood-forming tissues in the body. Myelofibrosis belongs to a group of diseases called myeloproliferative disorders. Many people with myelofibrosis get progressively worse, ...

  4. Successful treatment by selective arterial embolization of severe retroperitoneal hemorrhage secondary to bone marrow biopsy in post-polycythemic myelofibrosis.

    PubMed

    Arellano-Rodrigo, E; Real, M I; Muntañola, A; Burrel, M; Rozman, M; Fraire, G V; Cervantes, F

    2004-01-01

    Severe retroperitoneal hemorrhage represents an infrequent and serious complication of bone marrow biopsy. A 53-year-old man, diagnosed with polycythemia vera 12 years earlier, was submitted to a bone marrow biopsy due to the appearance of anemia with clinical and hematological features suggesting myelofibrotic transformation, a diagnosis that was confirmed by the marrow study. At 2 h of a right anterior iliac bone marrow trephine biopsy, the patient suddenly developed severe pain in the area of the biopsy, with antialgic flexion of the right leg. Computed tomographic (CT) scan of the abdomen showed a 5 x 9.5 cm hematoma in the right iliac and psoas muscles. The patient was initially managed with analgesics and transfusional support, but the pain persisted and a continuous fall in the hematocrit was observed in the following days. Angiographic examination of the right external iliac artery showed contrast extravasation arising from the circumflex iliac branch, which was embolized using polivinyl alcohol particles and one coil. Following such procedure, the patient recovered uneventfully and was discharged in good condition a few days later. This case illustrates the effectiveness of an endovascular approach in providing a fast and minimally invasive treatment for this life-threatening complication of bone marrow trephine biopsy.

  5. A phase II study of panobinostat in patients with primary myelofibrosis (PMF) and post-polycythemia vera/essential thrombocythemia myelofibrosis (post-PV/ET MF).

    PubMed

    Mascarenhas, John; Sandy, Lonette; Lu, Min; Yoon, James; Petersen, Bruce; Zhang, David; Ye, Fei; Newsom, Carrie; Najfeld, Vesna; Hochman, Tsivia; Goldberg, Judith D; Hoffman, Ronald

    2017-02-01

    Myelofibrosis is a chronic and progressive myeloproliferative neoplasm characterized by anemia, splenomegaly, debilitating symptoms and leukemic transformation. Ruxolitinib, an oral JAK1/2 inhibitor, is highly effective in ameliorating systemic symptoms and reducing splenomegaly. Current clinical research is focused on the evaluation of agents based on pre-clinical rationale that can result in disease course modification. Panobinostat is a pan-histone deacetylase inhibitor that has demonstrated clinical activity as a single agent in early phase trials of myelofibrosis. We previously conducted a phase I trial of panobinostat monotherapy in patients with myelofibrosis and determined 25mg thrice weekly as the recommended phase II dose. We then completed an investigator initiated, Simon 2-stage, phase II trial of 22 myelofibrosis patients at our single institution. After 6 cycles of therapy, the overall response rate by IWG-MRT criteria was 36% (8/22; 95% CI: 16-56%). The median percent reduction in spleen volume was 34% (range, 1.6%-73%) in eight evaluable patients. The average reduction in JAK2V617F allele burden was 6.8% (Range; -4.0% to 20.2%) and one patient obtained a complete molecular response. Six patients remained on therapy in the extension phase for a median of 18 months (range, 7-44). Treatment discontinuation was frequent due to patient/physician perception of therapy ineffectiveness. The optimal dosing of panobinostat for the treatment of MF remains somewhat ill-defined but appears to be most effective and better tolerated when administered at lower doses over a prolonged duration of therapy.

  6. Increased likelihood of post-polycythemia vera myelofibrosis in Ph-negative MPN patients with chromosome 12 abnormalities

    PubMed Central

    Benton, Christopher B; Tanaka, Maria; Wilson, Catherine; Pierce, Sherry; Zhou, Lingsha; Cortes, Jorge; Kantarjian, Hagop; Verstovsek, Srdan

    2016-01-01

    Chromosome 12 (Chr12) abnormalities have been described for individual patients with Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-neg MPN), however the frequency, characteristics, and outcomes of such patients as a whole have not been investigated. We reviewed a database of 1787 consecutive Ph-neg MPN patients seen at our institution and determined that 2% of Ph-neg MPN patients harbored an alteration involving Chr12 by cytogenetic evaluation. Retrospective chart review revealed that patients with Chr12 abnormalities had a higher likelihood of having myelofibrosis (MF) compared to patients without a Chr12 abnormality, and were more likely to have post-polycythemia vera MF. The most common alterations in Chr12 in MF patients involved 12q13, 12q15, 12q24, and trisomy 12, and >40% of Chr12 Ph-neg MPN patients had cytogenetic evolution. Chr12 abnormalities did not significantly correlate with JAK2 status, progression to acute myeloid leukemia, or survival, however patients with 12q24 abnormalities trended towards poorer outcomes. PMID:25687833

  7. A data-driven network model of primary myelofibrosis: transcriptional and post-transcriptional alterations in CD34+ cells

    PubMed Central

    Calura, E; Pizzini, S; Bisognin, A; Coppe, A; Sales, G; Gaffo, E; Fanelli, T; Mannarelli, C; Zini, R; Norfo, R; Pennucci, V; Manfredini, R; Romualdi, C; Guglielmelli, P; Vannucchi, A M; Bortoluzzi, S

    2016-01-01

    microRNAs (miRNAs) are relevant in the pathogenesis of primary myelofibrosis (PMF) but our understanding is limited to specific target genes and the overall systemic scenario islacking. By both knowledge-based and ab initio approaches for comparative analysis of CD34+ cells of PMF patients and healthy controls, we identified the deregulated pathways involving miRNAs and genes and new transcriptional and post-transcriptional regulatory circuits in PMF cells. These converge in a unique and integrated cellular process, in which the role of specific miRNAs is to wire, co-regulate and allow a fine crosstalk between the involved processes. The PMF pathway includes Akt signaling, linked to Rho GTPases, CDC42, PLD2, PTEN crosstalk with the hypoxia response and Calcium-linked cellular processes connected to cyclic AMP signaling. Nested on the depicted transcriptional scenario, predicted circuits are reported, opening new hypotheses. Links between miRNAs (miR-106a-5p, miR-20b-5p, miR-20a-5p, miR-17-5p, miR-19b-3p and let-7d-5p) and key transcription factors (MYCN, ATF, CEBPA, REL, IRF and FOXJ2) and their common target genes tantalizingly suggest new path to approach the disease. The study provides a global overview of transcriptional and post-transcriptional deregulations in PMF, and, unifying consolidated and predicted data, could be helpful to identify new combinatorial therapeutic strategy. Interactive PMF network model: http://compgen.bio.unipd.it/pmf-net/. PMID:27341078

  8. Palliative splenic irradiation in primary and post PV/ET myelofibrosis: outcomes and toxicity of three radiation schedules

    PubMed Central

    Federico, Mario; Pagnucco, Guido; Russo, Antonio; Cardinale, Giovanni; Guerrieri, Patrizia; Sciumè, Francesco; Symonds, Catherine; Cito, Letizia; Siragusa, Sergio; Gebbia, Nicola; Lagalla, Roberto; Midiri, Massimo; Giordano, Antonio; Montemaggi, Paolo

    2009-01-01

    Splenectomy and splenic irradiation (SI) are the sole treatment modalities to control drug resistant splenomegaly in patients with myelofibrosis (MF). SI has been used in poor surgical candidates but optimal total dose and fractionation are unclear. We retrospectively reviewed 14 MF patients with symptomatic splenomegaly. Patients received a median of 10 fractions in two weeks. Fraction size ranged from 0.2–1.4 Gy, and total dose varied from 2–10.8 Gy per RT course. Overall results indicate that 81.8% of radiation courses achieved a significant spleen reduction. Splenic pain relief and gastrointestinal symptoms reduction were obtained in 94% and 91% of courses, respectively. Severe cytopenias occurred in 13% of radiation courses. Furthermore patients were divided in three groups according to the radiation dose they received: 6 patients in the low-dose group (LDG) received a normalized dose of 1.67 Gy; 4 patients in the intermediate-dose group (IDG) received a normalized dose 4.37 Gy; the remaining 4 patients in the high-dose group (HDG) received a normalized dose of 9.2 Gy. Subgroup analysis showed that if no differences in terms of treatment efficacy were seen among dose groups, hematologic toxicity rates distributed differently. Severe cytopenias occurred in 50% of courses in the HDG, and in the 14.3% and in 0% of the IDG and LDG, respectively. Spleen reduction and pain relief lasted for a median of 5.5 months in all groups. Due to the efficacy and tolerability of the low-dose irradiation 4 patients from the LDG and IDG were retreated and received on the whole 12 RT courses. Multiple retreatments did not show decremental trends in terms of rates of response to radiation nor in terms of duration of clinical response. Moreover, retreatment courses did not cause an increased rate of adverse effects and none of the retreated patients experienced severe hematologic toxicities. The average time of clinical benefit in retreated patients was much longer (21 months

  9. PRCA with myelofibrosis: an unusual case report.

    PubMed

    Kar, Rakhee; Mahapatra, Manoranjan; Pati, Hara P

    2008-03-01

    The association of PRCA and myelofibrosis is very rare with only two such cases reported in the literature. Leukemic transformation in myelofibrosis is known but the progression of PRCA to acute leukemia is very rare. We present an unusual case of PRCA with myelofibrosis which after 14 months of transfusion dependent anemia transformed to acute monocytic leukemia.

  10. The evolution and clinical relevance of prognostic classification systems in myelofibrosis.

    PubMed

    Bose, Prithviraj; Verstovsek, Srdan

    2016-03-01

    Primary myelofibrosis, the most aggressive of the classic Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), is a clonal disorder characterized by often debilitating constitutional symptoms and splenomegaly, bone marrow fibrosis and resultant cytopenias, extramedullary hematopoiesis, risk of leukemic transformation, and shortened survival. Post-polycythemia vera and post-essential thrombocythemia myelofibrosis represent similar entities, although some differences are being recognized. Attempts to classify patients with myelofibrosis into prognostic categories have been made since the late 1980s, and these scoring systems continue to evolve as new information becomes available. Over the last decade, the molecular pathogenesis of MPNs has been elucidated considerably, and the Janus kinase (JAK) 1/2 inhibitor ruxolitinib is the first drug specifically approved by the US Food and Drug Administration to treat patients with intermediate-risk and high-risk myelofibrosis. This article reviews the evolution of prognostic criteria in myelofibrosis, emphasizing the major systems widely in use today, as well as recently described, novel systems that incorporate emerging data regarding somatic mutations. Risk factors for thrombosis and conversion to MPN blast phase also are discussed. Finally, the practical usefulness of the current prognostic classification systems in terms of clinical decision making is discussed, particularly within the context of some of their inherent weaknesses. Cancer 2016;122:681-692. © 2015 American Cancer Society.

  11. Radioimmunoassay of erythropoietin: circulating levels in normal and polycythemic human beings

    SciTech Connect

    Garcia, J.F.; Ebbe, S.N.; Hollander, L.; Cutting, H.O.; Miller, M.E.; Cronkite, E.P.

    1982-05-01

    Techniques are described in detail for the RIA of human Ep in unextracted plasma or serum. With 100 ..mu..l of sample, the assay is sensitive at an Ep concentration of approximately 4 mU/ml, and when required, the sensitivity can be increased to 0.4 mU/ml, a range considerably less than the concentration observed in normal human beings. This is approximately 100 times more sensitive than existing in vivo bioassays for this hormone. Studies concerned with the validation of the Ep RIA show a high degree of correlation with the polycythemic mouse bioassay. Dilutions of a variety of human serum samples show a parallel relationship with the standard reference preparation for Ep. Validation of the RIA is further confirmed by observations of appropriate increases or decreases of circulating Ep levels in physiological and clinical conditions known to be associated with stimulation or suppression of Ep secretion. Significantly different mean serum concentrations of 17.2 mU/ml for normal male subjects and 18.8 mU/ml for normal female subjects were observed. Mean plasma Ep concentrations in patients with polycythemia vera are significantly decreased, and those of patients with secondary polycythemia are significantly increased as compared to plasma levels in normal subjects. These results demonstrate an initial practical value of the Ep RA in the hematology clinic, which will most certainly be expanded with its more extensive use.

  12. Recombinant interferon-α in myelofibrosis reduces bone marrow fibrosis, improves its morphology and is associated with clinical response.

    PubMed

    Pizzi, Marco; Silver, Richard T; Barel, Ariella; Orazi, Attilio

    2015-10-01

    Recombinant interferon-α represents a well-established therapeutic option for the treatment of polycythemia vera and essential thrombocythemia. Recent studies also suggest a role for recombinant interferon-α in the treatment of 'early stage' primary myelofibrosis, but few studies have reported the bone marrow changes after clinically successful interferon therapy. The aim of the present study is to detail the histological responses to recombinant interferon-α in primary myelofibrosis and post-polycythemia vera/post-essential thrombocythemia myelofibrosis and to correlate these with clinical findings. We retrospectively studied 12 patients with primary myelofibrosis or post-polycythemia vera/post-essential thrombocythemia myelofibrosis, who had been treated with recombinant interferon-α. Six patients had received other prior cytoreductive therapies. Bone marrow biopsy was assessed for the following histological parameters: (i) cellularity; (ii) myeloid-to-erythroid ratio; (iii) megakaryocyte tight clusters; (iv) megakaryocyte and naked nuclei density; (v) megakaryocytic atypia; (vi) fibrosis; and (vii) the percentage of blasts. Clinical and laboratory data were included: (i) constitutional symptoms; (ii) splenomegaly, if present; and (iii) complete cell blood count. The clinical response to therapy was evaluated using the International Working Group for Myelofibrosis Research and Treatment/European LeukemiaNet response criteria. The Dynamic International Prognostic Scoring System (DIPSS) score was calculated before and after recombinant interferon-α administration. Successful interferon therapy for myelofibrosis was associated with a significant reduction of marrow fibrosis, cellularity, megakaryocyte density and naked nuclei density. The presence of JAK2(V617F) mutation correlated with improved DIPSS score. JAK2(V617F)-negative cases showed worsening of such score or evolution to acute myeloid leukemia. Cytogenetic analysis documented a normal karyotype in all

  13. Erythropoietin assay: present status of methods, pitfalls, and results in polycythemic disorders.

    PubMed

    Popovic, W J; Adamson, J W

    1978-01-01

    Mammalian erythropoiesis is regulated primarily by the hormone erythropoietin (ESP). Studies of ESF have provided information about its biochemistry and its role in regulating hemoglobin synthesis. Such studies rely on assays for erythropoietic activity in biological fluid. The assay which has proven most valuable and is used most widely is based upon the incorporation of radioactive iron into newly-formed red cells of polycythemic mice. While this assay has gained wide acceptance, it is expensive, cumbersome, imprecise, and insensitive, capable of reliably detecting no less than 50 milliunits of erythropoietin. Improvements in assay techniques will require new methodology relying primarily on immunologic recognition for the determination of hormone activity. Currently under development and in experimental use are radioimmunoassays and a hemagglutination inhibition assay. While work has progressed in these areas, these assays are not of proven value at present and meaningful physiological correlations have not emerged from their use. Alternatively, assays for hormone activity using suspensions of hematopoietic cells and the measurement of incorporation of radioactive isotopes into hemoglobin have provided both improvement in sensitivity and precision. The disadvantage of these types of assays is that they are sensitive to factors other than ESF and may give misleading information, depending on whether the factors present stimulate or inhibit cellular proliferation and hemoglobin synthesis. While such techniques may provide a temporary solution to some problems associated with assaying ESF for purification or physiological studies, they are not the best answer to the overall problem of hormone detection and characterization. The most important contribution to this field will be the availability of large amounts of highly purified and well-characterized ESF.

  14. Fludarabine Phosphate and Total Body Irradiation Followed by a Donor Peripheral Stem Cell Transplant in Treating Patients With Myelodysplastic Syndromes or Myeloproliferative Disorders

    ClinicalTrials.gov

    2017-03-06

    Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Essential Thrombocythemia; Myeloproliferative Neoplasm; Paroxysmal Nocturnal Hemoglobinuria; Polycythemia Vera; Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase; Primary Myelofibrosis; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Ring Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts

  15. Therapeutic approaches in myelofibrosis and myelodysplastic/myeloproliferative overlap syndromes

    PubMed Central

    Sochacki, Andrew L; Fischer, Melissa A; Savona, Michael R

    2016-01-01

    The discovery of JAK2V617F a decade ago led to optimism for a rapidly developing treatment revolution in Ph− myeloproliferative neoplasms. Unlike BCR–ABL, however, JAK2 was found to have a more heterogeneous role in carcinogenesis. Therefore, for years, development of new therapies was slow, despite standard treatment options that did not address the overwhelming symptom burden in patients with primary myelofibrosis (MF), post-essential thrombocythemia MF, post-polycythemia vera MF, and myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) syndromes. JAK–STAT inhibitors have changed this, drastically ameliorating symptoms and ultimately beginning to show evidence of impact on survival. Now, the genetic foundations of myelofibrosis and MDS/MPN are rapidly being elucidated and contributing to targeted therapy development. This has been empowered through updated response criteria for MDS/MPN and refined prognostic scoring systems in these diseases. The aim of this article is to summarize concisely the current and rationally designed investigational therapeutics directed at JAK–STAT, hedgehog, PI3K–Akt, bone marrow fibrosis, telomerase, and rogue epigenetic signaling. The revolution in immunotherapy and novel treatments aimed at previously untargeted signaling pathways provides hope for considerable advancement in therapy options for those with chronic myeloid disease. PMID:27143923

  16. Calreticulin mutation burden--is it a stable clone in patients with essential thrombocythemia and myelofibrosis?

    PubMed

    Shuly, Yulia; Nagar, Meital; Ben-Asaf, Lior; Kneller, Abraham; Steinberg, David M; Amariglio, Ninette; Salomon, Ophira

    2015-12-01

    Calreticulin mutation represents the second most frequent mutation after JAK2 V617F in myeloproliferative disorder and is considered to be a driving mutation. Herein the mutation burden was evaluated in patients with essential thrombocythemia or myelofibrosis and found to increase by 5.7% over time unrelated to the time elapsed from the initial to the final positive test. The longer the course of the disease when first tested (range 0-30 years, mean 7.9 years) the lower mutation burden was observed. The mutated clone was larger in type II in comparison with type I mutation when first tested but the difference in mutation burden from the final to the first positive test was significantly higher in those with type I. Similarly, the difference in mutation burden was higher in patients with essential thrombocythemia reaching almost 8% in comparison to 1.3% in post-essential thrombocythemia myelofibrosis. Thus a repeat calreticulin quantitative test is not warranted.

  17. Magnetic resonance imaging in myelofibrosis and essential thrombocythaemia: contribution to differential diagnosis.

    PubMed

    Rozman, C; Cervantes, F; Rozman, M; Mercader, J M; Montserrat, E

    1999-03-01

    To ascertain the value of magnetic resonance (MR) imaging in the differential diagnosis between myelofibrosis (MF) and essential thrombocythaemia (ET), 38 patients were analysed. 20 patients had MF (idiopathic myelofibrosis, 15 cases; post-ET myelofibrosis, four cases; post-polycythaemic MF, one case) and 18 ET. Mean age was 61.5 years (range 30-89) for patients with MF and 60.9 years (range 26-83) for ET patients. MR imaging was performed in the dorsal vertebrae in all cases, and also in both femurs in 2 5 of the patients. In most ET cases the MR signal of the dorsal vertebrae was not modified, whereas it was markedly reduced in MF (P=0.0000001). With regard to femoral marrow, it was usually fatty in ET, with an absent to moderate degree of reconversion seen in the 14 cases analysed, contrasting with the marked degree of reconversion noted in 10/11 patients with MF (P=0.000007). An inverse correlation was demonstrated between the vertebral signal and the degree of femoral reconversion. These differences were due to the fact that in ET the bone marrow adipose tissue is grossly preserved, whereas in MF it is usually markedly decreased or absent. The above results indicate that MR imaging is a useful tool for the differential diagnosis of ET and MF, with the usefulness of this technique increasing when vertebral and femoral bone marrow studies are combined.

  18. Primary autoimmune myelofibrosis: definition of a distinct clinicopathologic syndrome.

    PubMed

    Pullarkat, Vinod; Bass, Randall D; Gong, Jerald Z; Feinstein, Donald I; Brynes, Russell K

    2003-01-01

    Myelofibrosis is characterized by reticulin fibrosis of the bone marrow with resulting features of myelophthisis. Besides hematopoietic malignancies and other neoplasms involving the bone marrow, myelofibrosis has been described in association with autoimmune disorders, especially systemic lupus erythematosus. We describe the clinicopathologic features of a primary form of autoimmune myelofibrosis (AIMF) in patients who do not have systemic lupus erythematosus or another well-defined autoimmune syndrome. Absence of marked splenomegaly, peripheral blood cytopenias with mild teardrop poikilocytosis and leukoerythroblastosis, bone marrow lymphoid aggregates, and presence of autoantibodies are some of the salient features of primary AIMF. AIMF should especially be differentiated from chronic idiopathic myelofibrosis, a neoplastic myeloproliferative disease. Primary AIMF appears to have an excellent prognosis, with all patients reported in this series responding to a short course of corticosteroid therapy.

  19. Idiopathic myelofibrosis associated with ulcerative colitis.

    PubMed

    Arellano-Rodrigo, Eduardo; Esteve, Jordi; Giné, Eva; Panés, Julián; Cervantes, Francisco

    2002-07-01

    A patient with ulcerative colitis (UC) who developed idiopathic myelofibrosis (IM) is reported. The initial diagnosis of UC was established by colonoscopy and large bowel biopsy, performed after a one-month history of abdominal pain and bloody diarrhea. The patient showed a favorable response to prednisone and mesalamine treatment and six months later he developed a new episode of UC, which was successfully controlled with treatment. However, two years later splenomegaly and anemia were observed, with aniso-poikilocytosis, tear-drop cells, immature myeloid precursors in the peripheral blood, and increased serum LDH, arising the suspicion of IM, a diagnosis that was confirmed by bone marrow biopsy. The present case represents a new association of IM with an autoimmune disease and gives support to the hypothesis of a possible immune basis of some IM cases.

  20. Idiopathic myelofibrosis associated with primary biliary cirrhosis.

    PubMed

    Hernández-Boluda, J C; Jiménez, M; Rosiñol, L; Cervantes, F

    2002-03-01

    A patient with primary biliary cirrhosis (PBC) who developed idiopathic myelofibrosis (IM) is reported. The initial diagnosis of PBC was established by liver biopsy, performed after a 2-month history of constitutional symptoms associated with abnormalities of the serum liver enzymes, with typical serum immunological markers being found. Although a favorable response of PBC to prednisone was observed, one and a half year later the patient developed anemia with anisocytosis and poikilocytosis, tear-drop cells, and leukoerythroblastic picture, and IM was diagnosed by bone marrow biopsy. A few months later, a rapid worsening of the patient's clinical condition was noted, with an increase in the constitutional symptoms and need for frequent packed RBC transfusions, and she finally died from an infectious complication. This case represents a new association of IM with an autoimmune disease, supporting the hypothesis of a possible immune basis of IM in some cases.

  1. Definition and management of ruxolitinib treatment failure in myelofibrosis.

    PubMed

    Pardanani, A; Tefferi, A

    2014-12-12

    Ruxolitinib, a Janus kinase (JAK)-1 and JAK-2 inhibitor, is the first-in-class drug to be licensed in the United States for the treatment of high- and intermediate-risk myelofibrosis (MF). Several other JAK inhibitors are in development with some currently undergoing phase-3 clinical trial testing. None of the currently available JAK inhibitors are specific to mutant JAK2; their mechanism of action involves attenuation of JAK-STAT signaling with downregulation of proinflammatory cytokines, rather than selective suppression of the disease clone. Accordingly, while ruxolitinib and other JAK inhibitors are effective in controlling splenomegaly and alleviating constitutional symptoms, their benefit in terms of reversing bone marrow fibrosis or inducing complete or partial remissions appears to be limited. The experience to date with ruxolitinib shows that despite its salutary effects on quality of life, over half of the patients discontinue treatment within 2-3 years. In the current perspective, we examine the incidence and causes of ruxolitinib 'treatment failure' in MF patients based on our personal experience as well as a review of the published literature. We also discuss the challenges in defining and classifying ruxolitinib failure, and within the context of several clinical scenarios, we provide recommendations for the post-ruxolitinib management of MF patients.

  2. Role of neoplastic monocyte-derived fibrocytes in primary myelofibrosis

    PubMed Central

    Bueso-Ramos, Carlos E.; Newberry, Kate J.; Knez, Liza; Post, Sean M.; Ahn, Jihae; Levine, Ross L.; Kantarjian, Hagop M.

    2016-01-01

    Primary myelofibrosis (PMF) is a fatal neoplastic disease characterized by clonal myeloproliferation and progressive bone marrow (BM) fibrosis thought to be induced by mesenchymal stromal cells stimulated by overproduced growth factors. However, tissue fibrosis in other diseases is associated with monocyte-derived fibrocytes. Therefore, we sought to determine whether fibrocytes play a role in the induction of BM fibrosis in PMF. In this study, we show that BM from patients with PMF harbors an abundance of clonal, neoplastic collagen- and fibronectin-producing fibrocytes. Immunodeficient mice transplanted with myelofibrosis patients’ BM cells developed a lethal myelofibrosis-like phenotype. Treatment of the xenograft mice with the fibrocyte inhibitor serum amyloid P (SAP; pentraxin-2) significantly prolonged survival and slowed the development of BM fibrosis. Collectively, our data suggest that neoplastic fibrocytes contribute to the induction of BM fibrosis in PMF, and inhibiting fibrocyte differentiation with SAP may interfere with this process. PMID:27481130

  3. Sunitinib in Treating Patients With Idiopathic Myelofibrosis

    ClinicalTrials.gov

    2014-05-12

    Accelerated Phase Chronic Myelogenous Leukemia; Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Mast Cell Leukemia; Meningeal Chronic Myelogenous Leukemia; Primary Myelofibrosis; Progressive Hairy Cell Leukemia, Initial Treatment; Prolymphocytic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage IV Chronic Lymphocytic Leukemia; T-cell Large Granular Lymphocyte Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Hairy Cell Leukemia

  4. Idiopathic myelofibrosis associated with classic polyarteritis nodosa.

    PubMed

    Camós, Mireia; Arellano-Rodrigo, Eduardo; Abelló, Deborah; Muntañola, Ana; Ferrer, Ana; Grau, Josep Maria; Cervantes, Francisco

    2003-03-01

    A woman with scleroderma and classic polyarteritis nodosa (PAN) who developed idiopathic myelofibrosis (IM) is reported. The patient presented with a one-year history of weakness, polyarthritis, Raynaud phenomenon, dry cough, and epigastralgia. The diagnosis of scleroderma with visceral involvement was made and treatment with prednisone subsequently started, with good clinical response. Six years later, fever, weight loss, livedo reticularis, and dysesthesias developed. Electromyographic studies were consistent with sensory neuropathy and a sural nerve biopsy yielded the diagnosis of PAN. The patient received cyclophosphamide plus prednisone with a favorable response, but 11 years later she was admitted because of weakness, constitutional symptoms, and abdominal pain due to spleen infarcts. Marked anemia, with aniso-poikilocytosis, tear-drop cells, immature myeloid precursors in the peripheral blood, and an increased serum LDH, was observed and the diagnosis of IM established by bone marrow biopsy. This case represents a new association between IM and an autoimmune disease and supports the hypothesis of an immune basis of IM in some patients.

  5. Unique features of primary myelofibrosis in Chinese.

    PubMed

    Xu, Zefeng; Gale, Robert Peter; Zhang, Yue; Qin, Tiejun; Chen, Huishu; Zhang, Peihong; Zhang, Tianjiao; Liu, Liu; Qu, Shiqiang; Xiao, Zhijian

    2012-03-15

    Clinical and laboratory features of 642 consecutive Chinese subjects with primary myelofibrosis (PMF) were analyzed and compared with those of 1054 predominately white subjects with PMF. Chinese subjects were significantly younger, fewer had constitutional symptoms, and fewer had a palpable spleen or liver. Anemia, in contrast, was significantly more common in Chinese as was an increased white blood cell count and low platelet count. The reason for these differences is unclear, but it does not seem to be correlated with delayed diagnosis. A small but significantly increased proportion of Chinese had the JAK2(V617F) mutation but no difference in the frequency of haplotypes associated with PMF in whites. Survival of Chinese with PMF was also significantly longer than that of whites with PMF. We found commonly used staging systems for PMF such as the International Prognostic Scoring System and the Dynamic International Prognostic Scoring System were suboptimal predictors of survival in Chinese with PMF, and we developed a revised prognostic score that should help in comparison of data between studies of PMF in different populations and planning of clinical trials.

  6. Efficacy of ALK5 inhibition in myelofibrosis

    PubMed Central

    Zhao, Wanke; Ho, Wanting Tina; Han, Ying; Murdun, Cem; Mailloux, Adam W.; Zhang, Ling; Wang, Xuefeng; Budhathoki, Anjali; Pradhan, Kith; Rapaport, Franck; Wang, Huaquan; Shao, Zonghong; Ren, Xiubao; Steidl, Ulrich; Levine, Ross L.; Zhao, Zhizhuang Joe; Verma, Amit; Epling-Burnette, Pearlie K.

    2017-01-01

    Myelofibrosis (MF) is a bone marrow disorder characterized by clonal myeloproliferation, aberrant cytokine production, extramedullary hematopoiesis, and bone marrow fibrosis. Although somatic mutations in JAK2, MPL, and CALR have been identified in the pathogenesis of these diseases, inhibitors of the Jak2 pathway have not demonstrated efficacy in ameliorating MF in patients. TGF-β family members are profibrotic cytokines and we observed significant TGF-β1 isoform overexpression in a large cohort of primary MF patient samples. Significant overexpression of TGF-β1 was also observed in murine clonal MPLW515L megakaryocytic cells. TGF-β1 stimulated the deposition of excessive collagen by mesenchymal stromal cells (MSCs) by activating the TGF-β receptor I kinase (ALK5)/Smad3 pathway. MSCs derived from MPLW515L mice demonstrated sustained overproduction of both collagen I and collagen III, effects that were abrogated by ALK5 inhibition in vitro and in vivo. Importantly, use of galunisertib, a clinically active ALK5 inhibitor, significantly improved MF in both MPLW515L and JAK2V617F mouse models. These data demonstrate the role of malignant hematopoietic stem cell (HSC)/TGF-β/MSC axis in the pathogenesis of MF, and provide a preclinical rationale for ALK5 blockade as a therapeutic strategy in MF.

  7. Correlation between erythropoietic activity and body growth rate in hypertransfused polycythemic growing rats as the result of an erythropoietin-dependent operating mechanism

    SciTech Connect

    Bozzini, C.E.; Alippi, R.M.; Barcelo, A.C.; Caro, J.

    1989-02-01

    The established relationship between erythropoietic activity and body growth rate in the polycythemic growing rat could be the result of either an erythropoietin (EPO)-dependent or an EPO-independent operating mechanism. The present study was thus undertaken to elucidate the nature of the aforementioned mechanism by assessing the ratio between plasma immunoreactive EPO (iEPO) concentration and erythropoietic activity in young hypertransfused rats for different body growth rates. Red blood cell (RBC)-59Fe uptake was about 75% in 21-day-old rats; it rapidly decreased with time when the animals were placed on a protein-free diet, approaching a level of about 1% by the 10th day of protein starvation. Over the same period plasma iEPO decreased from 55 mU/ml to 7 mU/ml. Body growth rate was 0. Following this ''protein depletion period'' the rats received diets containing different amounts of casein (''protein repletion period'') added isocalorically to the protein-free diet to elicit a rise in body growth rate. Statistically significant relationships (p less than 0.001) were found between dietary casein concentration and body growth rate (r = 0.991), dietary casein concentration and RBC-59Fe uptake (r = 0.991), dietary casein concentration and plasma iEPO level (r = 0.992), body growth rate and RBC-59Fe (r = 0.986), and body growth rate and plasma iEPO level (r = 0.994) in hypertransfused polycythemic rats during the protein repletion period. These findings suggest that the correlation between erythropoietic activity and growth rate in the growing rat is the result of an erythropoietin-dependent operating mechanism, which appears to be independent of the ratio tissue oxygen supply/tissue oxygen demand.

  8. Spinal cord compression due to extramedullary haemopoiesis in myelofibrosis.

    PubMed Central

    Cook, G; Sharp, R A

    1994-01-01

    Extramedullary haemopoiesis resulting in spinal cord compression is rare. This report of extramedullary myeloid metaplasia in a patient with myelofibrosis serves to illustrate the value of magnetic resonance imaging (MRI) in the diagnosis and management of good neurological recovery. Images PMID:8027402

  9. [Acute panmyelosis with myelofibrosis: a rare cause of pancytopenia].

    PubMed

    Falé, Cláudia; Araújo, Ana; Lourenço, Sílvia; Pais, Maria

    2013-01-01

    Acute Panmyelosis with myelofibrosis is a rare and aggressive acute myeloid leukemia accounting for 2% of all acute leukemias. Clinically, it is characterized by an acute onset of cytopenias associated with extensive bone marrow fibrosis in the absence of splenomegaly and related morphological changes in the red blood cells such as dacryocytes. The presence of fibrosis further complicates the correct diagnosis of this rare disease, being important to differentiate this entity from other hematologic malignancies such as other acute myeloid leukemias and myelodysplastic syndromes associated with myelofibrosis. We report a case of a young adult of 16 years old, admitted with severe pancytopenia. The exposure of this case is justified by the rarity of this pathology associated with few cases reported in medical literature, allowing for a clinical sharing and a better understanding of the different clinical aspects of this entity of difficult diagnosis.

  10. Intrinsic resistance to JAK2 inhibition in myelofibrosis

    PubMed Central

    Kalota, Anna; Jeschke, Grace R.; Carroll, Martin; Hexner, Elizabeth O.

    2013-01-01

    Purpose Recent results have demonstrated that myeloproliferative neoplasms (MPN) are strongly associated with constitutive activation of the JAK2 tyrosine kinase. However, JAK2 inhibitors currently approved or under development for treating myeloproliferative neoplasms do not selectively deplete the malignant clone, and the inhibition of activity of the drug target (JAK2) has not been rigorously evaluated in clinical studies. Therefore in this study we developed an in vitro assay to gain insight into how effectively JAK2 activity is inhibited in patient samples. Experimental Design We treated primary cells from normal donors and patients with MPN with JAK2 inhibitors and measured phosphorylation of downstream targets STAT5 and STAT3 by flow cytometry. Obtained results were next correlated with JAK2 V617F allele burden and plasma cytokines level. Results We observed a dose-dependent decrease in pSTAT5 and pSTAT3 in ex vivo treated granulocytes. However, phosphorylation of STAT3 and STAT5 in cells from patients with myelofibrosis was significantly less inhibited when compared to cells from patients with polycythemia vera, essential thrombocytosis, and normal donors. Sensitivity to inhibition did not correlate with JAK2 V617F clonal burden. Mixing studies using plasma from patients with myelofibrosis did not transfer resistance to sensitive cells. Likewise, no single cytokine measured appeared to account for the observed pattern of resistance. Taken together these observations suggest that there are cell intrinsic mechanisms that define a priori resistance to JAK2 inhibition in myelofibrosis, and the lesion is localized upstream of STAT3 and STAT5. PMID:23386690

  11. A rare cause of cytopenia in a patient with systemic lupus erythematosus: Autoimmune myelofibrosis

    PubMed Central

    Cansu, Döndü Üsküdar; Teke, Hava Üsküdar; Korkmaz, Cengiz

    2017-01-01

    Hematological abnormalities are very common in the course of systemic lupus erythematosus (SLE). Myelofibrosis is a bone marrow disorder in which there is excessive fibrous tissue formation in the bone marrow. Various benign and malignant disorders can cause or be associated with a diffuse increase in the bone marrow reticular tissue. Some diseases such as infections, neoplasms, and autoimmune diseases may also induce bone marrow fibrosis (secondary myelofibrosis). Cytopenia from autoimmune myelofibrosis (AIMF) in SLE is a rare condition. Here we present a case of AIMF associated with SLE and aim to emphasize on the other cause of cytopenia in SLE. PMID:28293461

  12. Colorectal Liver Metastasis, Primary Gallbladder Carcinoma and Myelofibrosis Present Simultaneously in a Liver Resection Specimen

    PubMed Central

    Gray, Sophie A.; Raber, Menno H.; Provoost, Esther; Toes, Gert-Jan; Klaase, Joost M.

    2015-01-01

    Myelofibrosis and gallbladder carcinoma are both very rare diseases. This case report describes a patient with a history of myelofibrosis and colorectal carcinoma who was diagnosed with colorectal liver metastases. Surgery was performed to remove the metastases, and on site, the gallbladder was removed because of involvement in one of the liver lesions. After pathological examination, a primary gallbladder carcinoma and myelofibrosis were found in addition to the liver metastases. The combination of diseases was not likely to be interconnected but rather an unlucky course of events for the patient. PMID:26600770

  13. Treatment and management of myelofibrosis in the era of JAK inhibitors.

    PubMed

    Keohane, Clodagh; Radia, Deepti H; Harrison, Claire N

    2013-01-01

    Myelofibrosis (MF) can present as a primary disorder or evolve from polycythemia vera (PV) or essential thrombocythemia (ET) to post-PV MF or post-ET MF, respectively. MF is characterized by bone marrow fibrosis, splenomegaly, leukoerythroblastosis, extramedullary hematopoiesis, and a collection of debilitating symptoms. Until recently, the therapeutic options for patients with MF consisted of allogeneic hematopoietic stem cell transplant (alloHSCT), the use of cytoreductive agents (ie, hydroxyurea), splenectomy and splenic irradiation for treatment of splenomegaly, and management of anemia with transfusions, erythropoiesis-stimulating agents (ESAs), androgens, and immunomodulatory agents. However, with increased understanding of the pathogenesis of MF resulting from dysregulated Janus kinase (JAK) signaling, new targeted JAK inhibitor therapies, such as ruxolitinib, are now available. The purpose of this article is to review the clinical features of MF, discuss the use and future of JAK inhibitors, reassess when and how to use conventional MF treatments in the context of JAK inhibitors, and provide a perspective on the future of MF treatment.

  14. Treatment and management of myelofibrosis in the era of JAK inhibitors

    PubMed Central

    Keohane, Clodagh; Radia, Deepti H; Harrison, Claire N

    2013-01-01

    Myelofibrosis (MF) can present as a primary disorder or evolve from polycythemia vera (PV) or essential thrombocythemia (ET) to post-PV MF or post-ET MF, respectively. MF is characterized by bone marrow fibrosis, splenomegaly, leukoerythroblastosis, extramedullary hematopoiesis, and a collection of debilitating symptoms. Until recently, the therapeutic options for patients with MF consisted of allogeneic hematopoietic stem cell transplant (alloHSCT), the use of cytoreductive agents (ie, hydroxyurea), splenectomy and splenic irradiation for treatment of splenomegaly, and management of anemia with transfusions, erythropoiesis-stimulating agents (ESAs), androgens, and immunomodulatory agents. However, with increased understanding of the pathogenesis of MF resulting from dysregulated Janus kinase (JAK) signaling, new targeted JAK inhibitor therapies, such as ruxolitinib, are now available. The purpose of this article is to review the clinical features of MF, discuss the use and future of JAK inhibitors, reassess when and how to use conventional MF treatments in the context of JAK inhibitors, and provide a perspective on the future of MF treatment. PMID:23990704

  15. Hypocellular myelodysplastic syndrome with myelofibrosis in acute myeloid leukemia transformation: A case report.

    PubMed

    Song, Kui; Xu, Xiaojun; Li, Min

    2015-07-01

    Primary myelodysplastic syndrome (MDS) with myelofibrosis is a rare hematological disorder that should be classified as a distinct subgroup of MDS. Treatment of MDS with myelofibrosis remains problematic and the prognosis is poor in these patients, particularly following transformation into acute myeloid leukemia (AML). The current study presents the case of a 28-year-old male diagnosed with MDS associated with myelofibrosis, together with hypocellular bone marrow features. Following induction chemotherapy consisting of mitoxantrone and cytarabine, the patient achieved complete remission, but developed severe myelofibrosis. The patient relapsed and the disease transformed into AML 12 months later. However, the extent of the myelofibrosis was markedly alleviated upon administration of a FLAG regimen that consisted of fludarabine, cytarabine and granulocyte colony-stimulating factor during the AML transformation. After one course of the FLAG regimen, the patient achieved a second complete remission. As there was no suitable donor for hematopoietic stem cell transplantation (HSCT), the patient relapsed and succumbed shortly after. In conclusion, MDS with fibrosis is an aggressive disease, but the degree of myelofibrosis may not be associated with the progression of hypocellular MDS, and allogeneic HSCT remains a potentially curative option for affected patients.

  16. Comorbidities predict worse prognosis in patients with primary myelofibrosis

    PubMed Central

    Newberry, Kate J.; Naqvi, Kiran; Nguyen, Khanh T.; Cardenas-Turanzas, Marylou; Tanaka, Maria Florencia; Pierce, Sherry; Verstovsek, Srdan

    2016-01-01

    Background Comorbidities have been shown to play an important role in prognostic assessment of several hematologic conditions; however, the role of comorbidities in primary myelofibrosis has not been studied. The aim of our study was to evaluate the prevalence and impact of comorbidities in patients with primary myelofibrosis (PMF) using the Adult Comorbidity Evaluation-27 (ACE-27). Methods In this retrospective observational cohort study, we evaluated 349 consecutive patients with a confirmed diagnosis of PMF who presented to our institution from 2000 to 2008. We evaluated the frequency and severity of comorbidities in these patients and assessed their impact on survival in a bivariable model that included the ACE-27 and Dynamic International Prognostic Scoring System (DIPSS) scores as covariates. Results Sixty-four percent of patients had at least one comorbid condition, and diseases of the cardiovascular system (63%) were most common. Comorbidities had a significant negative impact on survival (P < 0.001). Patients with severe comorbidities had twice the risk of death as those with no comorbidities. When stratified by demographic and clinical characteristics, comorbidities were significantly associated with worse survival in patients younger than 65 years (P < 0.001) and those with performance status < 1 (P < 0.001). In a multivariable model that included the ACE-27 and Dynamic-International Prognostic Scoring System scores, comorbidities retained a significant association with shorter survival (P ≤ 0.001). Conclusions Assessment of comorbid conditions in patients with PMF, particularly those who are younger and with good performance status, has important implications for overall prognosis and treatment planning. PMID:24917509

  17. Multiple esophageal variceal ruptures with massive ascites due to myelofibrosis-induced portal hypertension

    PubMed Central

    Tokai, Koichi; Miyatani, Hiroyuki; Yoshida, Yukio; Yamada, Shigeki

    2012-01-01

    A 75-year old man had been diagnosed at 42 years of age as having polycythemia vera and had been monitored at another hospital. Progression of anemia had been recognized at about age 70, and the patient was thus referred to our center in 2008 where secondary myelofibrosis was diagnosed based on bone marrow biopsy findings. Hematemesis due to rupture of esophageal varices occurred in January and February of 2011. The bleeding was stopped by endoscopic variceal ligation. Furthermore, in March of the same year, hematemesis recurred and the patient was transported to our center. He was in irreversible hemorrhagic shock and died. The autopsy showed severe bone marrow fibrosis with mainly argyrophilic fibers, an observation consistent with myelofibrosis. The liver weighed 1856 g the spleen 1572 g, indicating marked hepatosplenomegaly. The liver and spleen both showed extramedullary hemopoiesis. Myelofibrosis is often complicated by portal hypertension and is occasionally associated with gastrointestinal hemorrhage due to esophageal varices. A patient diagnosed as having myelofibrosis needs to be screened for esophageal/gastric varices. Myelofibrosis has a poor prognosis. Therefore, it is necessary to carefully decide the therapeutic strategy in consideration of the patient’s concomitant conditions, treatment invasiveness and quality of life. PMID:22851873

  18. Clinical, histopathologic, and genetic features of pediatric primary myelofibrosis--an entity different from adults.

    PubMed

    DeLario, Melissa R; Sheehan, Andrea M; Ataya, Ramona; Bertuch, Alison A; Vega, Carlos; Webb, C Renee; Lopez-Terrada, Dolores; Venkateswaran, Lakshmi

    2012-05-01

    Primary myelofibrosis is a chronic myeloproliferative neoplasm characterized by cytopenias, leukoerythroblastosis, extramedullary hematopoiesis, hepatosplenomegaly and bone marrow fibrosis. Primary myelofibrosis is a rare disorder in adults; children are even less commonly affected by this entity, with the largest pediatric case series reporting on three patients. Most literature suggests spontaneous resolution of myelofibrosis without long term complications in the majority of affected children. We describe the clinical, pathologic, and molecular characteristics and outcomes of nineteen children with primary myelofibrosis treated in our center from 1984 to 2011. Most patients had cytopenia significant enough to require supportive therapy. No child developed malignant transformation and only five of the 19 children (26%) had spontaneous resolution of disease. Sequence analyses for JAK2V617F and MPLW515L mutations were performed on bone marrow samples from 17 and six patients, respectively, and the results were negative. In conclusion, analysis of this large series of pediatric patients with primary myelofibrosis demonstrates distinct clinical, hematologic, bone marrow, and molecular features from adult patients.

  19. Primary myelofibrosis and the myeloproliferative neoplasms: the role of individual variation.

    PubMed

    Stein, Brady L; Moliterno, Alison R

    2010-06-23

    The classic myeloproliferative neoplasms--essential thrombocytosis, polycythemia vera, and primary myelofibrosis--are acquired, clonal hematopoietic stem cell disorders characterized by an overproduction of mature blood cells, bone marrow hypercellularity, extramedullary hematopoiesis, a tendency for thrombosis, and, rarely, leukemic transformation. Despite being classified as neoplastic diseases, the myeloproliferative neoplasms are often characterized by longevity, with survival measured in decades, even in the absence of treatment. Primary myelofibrosis is the rarest of the myeloproliferative neoplasms, is the most obscure with regard to its pathophysiology, and carries the least favorable although highly variable natural history. The identification of molecular lesions specific to the myeloproliferative neoplasms, in particular JAK2 V617F, has broadened understanding of the common features within these disorders and has advanced diagnostic, prognostic, and therapeutic tools. This article highlights the challenges inherent in the management of primary myelofibrosis and presents an opportunity to address the basis of individual variation within a rare and complex disorder.

  20. Practical management of patients with myelofibrosis receiving ruxolitinib.

    PubMed

    Harrison, Claire; Mesa, Ruben; Ross, David; Mead, Adam; Keohane, Clodagh; Gotlib, Jason; Verstovsek, Srdan

    2013-10-01

    Myelofibrosis (MF) is characterized by bone marrow fibrosis, progressive anemia and extramedullary hematopoiesis, primarily manifested as splenomegaly. Patients also experience debilitating constitutional symptoms, including sequelae of splenomegaly, night sweats and fatigue. Ruxolitinib (INC424, INCB18424, Jakafi, Jakavi), a JAK1 and JAK2 inhibitor, was approved in November 2011 by the US FDA for the treatment of intermediate- or high-risk MF, and more recently in Europe and Canada for the treatment of MF-related splenomegaly or symptoms. These approvals were based on data from two randomized Phase III studies: COMFORT-I randomized against placebo, and COMFORT-II randomized against best available therapy. In these studies, ruxolitinib rapidly improved multiple disease manifestations of MF, reducing splenomegaly and improving quality of life of patients and potentially prolonging survival. However, as with other chemotherapies, ruxolitinib therapy is associated with some adverse events, such as anemia and thrombocytopenia. The aims of this article are to provide a brief overview of ruxolitinib therapy, to discuss some common adverse events associated with ruxolitinib therapy and to provide clinical management recommendations to maximize patients' benefit from ruxolitinib.

  1. Genomic diversity in myeloproliferative neoplasms: focus on myelofibrosis

    PubMed Central

    2015-01-01

    The classical myeloproliferative neoplasms (MPNs) are a group of clonal diseases comprising essential thrombocythaemia (ET), polycythaemia vera (PV) and primary myelofibrosis (PMF). PMF is the rarest disease sub type and has been challenging to address due to the lack of a specific genetic marker, inadequate risk identification models and a highly variable clinical course. Continuous efforts have over time, seen the inclusion of cytogenetic information in prognostic scoring models that have resulted in improved risk stratification models providing further rationale for therapeutic management. Technological advances using single nucleotide polymorphism arrays increased the detection of known and novel MPN related changes and variant detection by massively parallel sequencing provided a large scale screening tool for the multitude of somatic gene mutations that have more recently been described in MPN. Some of these mutations show an association with specific cytogenetic changes or phenotypes. While PMF occurs mainly in adults, it has also been described in paediatric cases and shows distinct histopathological, genetic and clinical features in comparison. This review provides an overview of the genomics landscape of PMF and current developments in MPN therapy. PMID:26835366

  2. Interleukin-10 inhibits autonomous myelopoiesis in patients with myelofibrosis.

    PubMed

    Geissler, Klaus; Jäger, Eva; Öhler, Leopold; Gisslinger, Heinz; Jäger, Ulrich; Lechner, Klaus

    2015-09-01

    The spontaneous formation of colony-forming units granulocyte/macrophage (CFU-GM) in semisolid cultures has been shown to be due to the endogenous release of cytokines and/or to the hypersensitivity of cells against growth factors. We have reported that increased autonomous CFU-GM growth is an in vitro characteristic of myelofibrosis (MF) which may reflect aberrant hematopoiesis in vivo. Because of its cytokine synthesis-inhibiting action, we speculated that interleukin-10 (IL-10) may inhibit pathological overproduction of myeloid cells in MF by suppression of autonomous myelopoiesis. In this study, IL-10 significantly inhibited autonomous CFU-GM formation in vitro from peripheral blood mononuclear cells (PB MNC) in 10 of 11 patients with MF tested. In all patients, there was a mean inhibition of 69% ranging from 35% to 100%. Suppression of autonomous CFU-GM formation by IL-10 was dose dependent and reversible by the addition of anti-IL-10 antibodies. Our results indicate that IL-10 is a potentially useful molecule to affect aberrant myelopoiesis in patients with MF.

  3. Myelofibrosis associated with prominent periosteal bone apposition. Report of two cases.

    PubMed

    Yu, J S; Greenway, G; Resnick, D

    1994-01-01

    Myelofibrosis is a myeloproliferative disorder that is characterized by splenomegaly and bone marrow replacement by fibrous tissue. The predominant radiographic feature is osteosclerosis; however, in rare instances, periosteal bone apposition or periostitis is apparent in the metaphysis of the distal femura and proximal tibiae. It has been suggested that periostitis, when associated with fever and bone pain, is indicative of more aggressive disease. We report this unusual radiographic finding and its similar appearance to hypertrophic osteoarthropathy in two patients with myelofibrosis. In our patients, the presence of periosteal bone apposition did not correlate with increased disease aggressiveness.

  4. Dynamic of bone marrow fibrosis regression predicts survival after allogeneic stem cell transplantation for myelofibrosis.

    PubMed

    Kröger, Nicolaus; Zabelina, Tatjana; Alchalby, Haefaa; Stübig, Thomas; Wolschke, Christine; Ayuk, Francis; von Hünerbein, Natascha; Kvasnicka, Hans-Michael; Thiele, Jürgen; Kreipe, Hans-Heinrich; Büsche, Guntram

    2014-06-01

    We correlate regression of bone marrow fibrosis (BMF) on day 30 and 100 after dose- reduced allogeneic stem cell transplantation (allo-SCT) in 57 patients with primary or post-essential thrombocythemia/polycythemia vera myelofibrosis with graft function and survival. The distribution of International Prognostic Scoring System (IPSS) risk score categories was 1 patient with low risk, 5 patients with intermediate-1 risk, 18 patients with intermediate-2 risk, and 33 patients with high risk. Before allo-SCT, 41 patients (72%) were classified as XXX [myclofibrosis (MF)]-3 and 16 (28%) were classified as MF-2 according to the World Health Organization criteria. At postengraftment day +30 (±10 days), 21% of the patients had near-complete or complete regression of BMF (MF-0/-1), and on day +100 (±20 days), 54% were MF-0/-1. The 5-year overall survival rate at day +100 was 96% in patients with MF-0/-1 and 57% for those with MF-2/-3 (P = .04). There was no difference in BMF regression at day +100 between IPSS high-risk and low/intermediate-risk patients. Complete donor cell chimerism at day +100 was seen in 81% of patients with MF-0/-1 and in 31% of those with MF-2/-3. Patients with MF-2/-3 at day +100 were more likely to be transfusion-dependent for either RBCs (P = .014) or platelets (P = .018). Rapid BMF regression after reduced-intensity conditioning allo-SCT resulted in a favorable survival independent of IPSS risk score at transplantation.

  5. Pathologic interaction between megakaryocytes and polymorphonuclear leukocytes in myelofibrosis.

    PubMed

    Schmitt, A; Jouault, H; Guichard, J; Wendling, F; Drouin, A; Cramer, E M

    2000-08-15

    Idiopathic myelofibrosis (MF) is a myeloproliferative syndrome characterized by an increase in bone marrow collagen. Megakaryocytes (Mks), which store growth factors in their alpha granules, are known to be involved in the pathogenesis of MF. Previously, mice given bone marrow grafts infected with a retrovirus carrying murine thrombopoietin (TPO) complementary DNA developed a disease resembling human idiopathic MF. In this study, we used this murine model (TPO mice) to determine whether release of alpha granules is responsible for fibroblast activation and development of fibrosis. The intracellular trafficking of several alpha-granule proteins (von Willebrand factor, fibrinogen, and transforming growth factor beta (TGF beta), which are stored in the granule matrix; and alpha(IIb)beta(3) integrin and P-selectin (CD62p), which are located in the alpha-granule membrane) was studied with immune electron microscopy in bone marrow Mks from TPO mice. P-selectin immunolabeling increased consistently and was occasionally found lining the demarcation membrane system. Evidence of extensive emperipolesis was also found in TPO mouse Mks, involving almost exclusively neutrophil and eosinophil polymorphonuclear (PMN) cells with altered morphologic features. In parallel, the host Mks had myeloperoxidase-positive granules scattered in their cytoplasm, associated with marked ultrastructural cytoplasmic alterations and ruptured alpha-granule membranes. Similar observations were made in bone marrow biopsy specimens from 12 patients with idiopathic MF; indeed, there was an increased rate of emperipolesis involving mostly PMN cells, abnormal P-selectin expression, and mutual subcellular PMN and Mk alterations. This study indicates that in idiopathic MF, abnormal P-selectin distribution in Mks induces selective sequestration of PMN cells. This results in a release of alpha-granular proteins and growth factors, which in turn induces fibroblast activation and fibrosis deposition. (Blood

  6. Targeting hedgehog signaling in myelofibrosis and other hematologic malignancies

    PubMed Central

    2014-01-01

    Treatment of myelofibrosis (MF), a BCR-ABL–negative myeloproliferative neoplasm, is challenging. The only current potentially curative option, allogeneic hematopoietic stem cell transplant, is recommended for few patients. The remaining patients are treated with palliative therapies to manage MF-related anemia and splenomegaly. Identification of a mutation in the Janus kinase 2 (JAK2) gene (JAK2 V617F) in more than half of all patients with MF has prompted the discovery and clinical development of inhibitors that target JAK2. Although treatment with JAK2 inhibitors has been shown to improve symptom response and quality of life in patients with MF, these drugs do not alter the underlying disease; therefore, novel therapies are needed. The hedgehog (Hh) signaling pathway has been shown to play a role in normal hematopoiesis and in the tumorigenesis of hematologic malignancies. Moreover, inhibitors of the Hh pathway have been shown to inhibit growth and self-renewal capacity in preclinical models of MF. In a mouse model of MF, combined inhibition of the Hh and JAK pathways reduced JAK2 mutant allele burden, reduced bone marrow fibrosis, and reduced white blood cell and platelet counts. Preliminary clinical data also suggest that inhibition of the Hh pathway, alone or in combination with JAK2 inhibition, may enable disease modification in patients with MF. Future studies, including one combining the Hh pathway inhibitor sonidegib and the JAK2 inhibitor ruxolitinib, are underway in patients with MF and will inform whether this combination approach can lead to true disease modification. PMID:24598114

  7. Primary hypertrophic osteoarthropathy with myelofibrosis and anemia: a case report and review of literature

    PubMed Central

    Li, Sheyu; Li, Qianrui; Wang, Qin; Chen, Decai; Li, Jianwei

    2015-01-01

    Primary hypertrophic osteoarthropathy (PHO) is a rare and usually benign disorder of bone and connective tissue growth. Here we present a 28-year-old male patient presenting to our hospital with PHO and symptomatic anemia. Bone marrow biopsy suggested myelofibrosis, a serious complication of PHO, which is often neglected upon admission, but may lead to life-threatening anemia. PMID:25785156

  8. Acute megakaryoblastic leukemia (acute 'malignant' myelofibrosis): An unusual cause of osteosclerosis

    SciTech Connect

    Karasick, S.; Karasick, D.; Schilling, J.

    1982-11-01

    Acute megakaryoblastic leukemia or acute 'malignant' myelosclerosis is an acute and rapidly progressive myeloproliferative syndrome characterized by minimal or absent splenomegaly, pancytopenia, diffuse marrow fibrosis, and circulating blasts of megakaryocytic origin. The disease must be differentiated from other hematologic malignancies especially myelofibrosis with myeloid metaplasia. The radiographic changes of osteosclerosis in our patient have not been previously reported in the literature.

  9. Construction of gene/protein interaction networks for primary myelofibrosis and KEGG pathway-enrichment analysis of molecular compounds.

    PubMed

    Sun, C G; Cao, X J; Zhou, C; Liu, L J; Feng, F B; Liu, R J; Zhuang, J; Li, Y J

    2015-12-08

    The objective of this study was the development of a gene/protein interaction network for primary myelofibrosis based on gene expression, and the enrichment analysis of KEGG pathways underlying the molecular complexes in this network. To achieve this, genes involved in primary myelofibrosis were selected from the OMIM database. A gene/protein interaction network for primary myelofibrosis was obtained through Cytoscape with the literature mining performed using the Agilent Literature Search plugin. The molecular complexes in the network were detected by ClusterViz plugin and KEGG pathway enrichment of molecular complexes was performed using DAVID online. We found 75 genes associated with primary myelofibrosis in the OMIM database. The gene/protein interaction network of primary myelofibrosis contained 608 nodes, 2086 edges, and 4 molecular complexes with a correlation integral value greater than 4. Molecular complexes involved in KEGG pathways are related to cytokine regulation, immune function regulation, ECM-receptor interaction, focal adhesion, actin cytoskeleton regulation, cell adhesion molecules, and other biological behavior of tumors, which can provide a reliable direction for the treatment of primary myelofibrosis and the bioinformatic foundation for further understanding the molecular mechanisms of this disease.

  10. Resolution of myelofibrosis-associated pulmonary arterial hypertension following allogeneic hematopoietic stem cell transplantation

    PubMed Central

    Iliescu, Cezar; Lopez-Mattei, Juan; Patel, Bela; Bashoura, Lara; Popat, Uday

    2016-01-01

    Abstract We present the case of a 62-year-old man with myelofibrosis-associated pulmonary arterial hypertension (PAH) who underwent allogeneic hematopoietic stem cell transplantation with subsequent resolution of disease and PAH. Right heart catheterization was used to guide PAH therapy before and after transplantation. Drug interactions, adverse effects, and renal insufficiency posed clinical challenges for the management of PAH-specific medications after transplantation. PAH improved soon after transplantation, and vasoactive medications were tapered off. Resolution of PAH was confirmed with repeat measurement of pulmonary hemodynamic characteristics. Although the etiology and pathophysiology for the resolution of PAH was unclear, the myelopulmonary pathophysiologic link was likely to have contributed. This is the first report describing resolution of myelofibrosis-associated PAH after allogeneic hematopoietic stem cell transplantation. PMID:28090305

  11. Bone and bone-marrow blood flow in chronic granulocytic leukemia and primary myelofibrosis

    SciTech Connect

    Lahtinen, R.; Lahtinen, T.; Romppanen, T.

    1982-03-01

    Blood flow in hematopoietic bone marrow and in nonhematopoietic bone has been measured with a Xe-133 washout method in 20 patients with chronic granulocytic leukemia (CGL) and in seven with primary myelofibrosis. Age-matched healthy persons served as controls. Bone-marrow blood flow in CGL was dependent upon the phase of the disease. In the metamorphosis phase, bone-marrow blood flow was high compared with that in the well-controlled phase. Apart from the initial phase, the mean values for bone blood flow in CGL were increased compared with the values of the healthy controls. In myelofibrosis the bone blood flow was also increased. Bone-marrow blood flow in these diseases was dependent upon the cellularity of bone marrow as measured morphometrically.

  12. Laparoscopically assisted splenectomy following preoperative splenic artery embolization using contour emboli for myelofibrosis with massive splenomegaly.

    PubMed

    Iwase, K; Higaki, J; Mikata, S; Tanaka, Y; Yoshikawa, M; Hori, S; Osuga, K; Kosugi, S; Tamaki, T; Kamiike, W

    1999-06-01

    Laparoscopically assisted splenectomy with an 8- to 10-cm left upper paramedian laparotomy was performed following preoperative splenic artery embolization using painless contour emboli (super absorbent polymer microsphere) with early successful results in two men (46 and 37 years old) with myelofibrosis accompanied by massive splenomegaly. Dissection around the lower part of the spleen and the hilum initially was performed intracorporeally with the usual laparoscopic view under 12 mm Hg pneumoperitoneum. The alternating changes of viewpoints between the direct view through an 8- to 10-cm incision and the usual laparoscopic view with or without application of a retraction method were effective for safe hilar devascularization. Preoperative splenic artery embolization at the distal site was effective for safe dissection around the enlarged spleen. The patients did not complain of pain before operation. Preoperative painless embolization and laparoscopically assisted splenectomy with small laparotomy promotes the feasibility and safety of minimally invasive splenectomy for myelofibrosis with massive splenomegaly.

  13. Hematologic improvements in a myelodysplastic syndromes with myelofibrosis (MDS-F) patient treated with azacitidine.

    PubMed

    Okamura, Daisuke; Matsuda, Akira; Ishikawa, Maho; Maeda, Tomoya; Tanae, Ken; Kohri, Mika; Takahashi, Naoki; Kawai, Nobutaka; Asou, Norio; Bessho, Masami

    2014-01-01

    Myelodysplastic syndromes with myelofibrosis (MDS-F) is a poor prognostic hematopoietic disorder. Azacitidine was shown to prolong survival of high-risk MDS patients. However, the effects of azacitidine on MDS-F have yet to be elucidated. Azacitidine was administered to a 74-year-old man with MDS-F at a dose of 75 mg/m(2)/daily subcutaneously for 7 days every 28 days. Hematologic improvements were observed according to the International Working Group 2006 criteria after 8 cycles of the azacitidine treatment, and complete remission was achieved after 14 cycles. The grade of myelofibrosis was also improved. The therapeutic activity of azacitidine was confirmed in our MDS-F patient.

  14. Autoimmune myelofibrosis with pancytopenia as a presenting manifestation of systemic lupus erythematosus responsive to mycophenolate mofetil.

    PubMed

    Ungprasert, P; Chowdhary, V R; Davis, M D; Makol, A

    2016-04-01

    Hematological abnormalities, such as anemia, leucopenia, and thrombocytopenia, secondary to peripheral destruction, are common in systemic lupus erythematosus (SLE). However, cytopenias from autoimmune myelofibrosis (AIMF) are extremely uncommon in SLE, with less than 40 reported cases in the literature. We report the case of a 33-year-old female who presented with bullous skin lesions and pancytopenia as the presenting manifestation of what was ultimately diagnosed as SLE with AIMF. She responded well to glucocorticoids and mycophenolate mofetil.

  15. Ruxolitinib is manageable in patients with myelofibrosis and severe thrombocytopenia: a report on 12 Danish patients.

    PubMed

    Bjørn, Mads Emil; Holmström, Morten Orebo; Hasselbalch, Hans Carl

    2016-01-01

    We report 12 Danish myelofibrosis patients who have been treated successfully with ruxolitinib despite having low platelet counts (< 50 × 10(9)/L) during their treatment-course. The majority of the patients experienced marked clinical improvement. Serious side effects were only recorded in a single patient. It is concluded that JAK-inhibition with ruxolitinib is manageable in patients with low platelet counts and should be considered in symptomatic patients who otherwise might not be candidates for treatment.

  16. Intense splenic 99mTc-MDP uptake in a patient with myelofibrosis.

    PubMed

    Chen, Ming; Liu, Chun; Yang, Jigang

    2013-12-01

    99mTc-MDP bone scan was performed in a 49-year-old woman with breast cancer. Whole-body bone scan showed multiple foci of increased MDP activity in the bone and intense splenic 99mTc-MDP uptake. Initial bone marrow aspiration in multiple locations yielded no blood cells. A subsequent bone marrow biopsy in the left anterior superior iliac spine showed myelofibrosis in addition to the known bone metastasis.

  17. Ruxolitinib: a new JAK1/2 inhibitor that offers promising options for treatment of myelofibrosis

    PubMed Central

    Ostojic, Alen; Vrhovac, Radovan; Verstovsek, Srdan

    2016-01-01

    Ruxolitinib (INCB018424) is the first potent, selective, oral inhibitor of JAK1 and 2 being developed for clinical use. Its major cellular and systemic effects are proliferation inhibition, apoptosis induction and reduction in cytokine plasma levels, all mediated by the drug's inhibition of JAKs' ability to phosphorylate STAT. In initial clinical trials of its use in myelofibrosis, ruxolitinib exhibited durable efficacy in reduction of splenomegaly and alleviation of constitutional symptoms. Patients also showed weight gain and improvement in general physical condition. The dose-limiting toxicity was thrombocytopenia. In preliminary findings of a Phase III trial in patients with primary, postpolycythemia-vera, or postessential- thrombocythemia myelofibrosis, administration at an initial dosage of 15 or 20 mg twice daily led to a spleen-volume response rate (≥35% reduction at 24 weeks) of 41.9 versus 0.7% for placebo (p < 0.0001); furthermore, 45.9% of the ruxolitinib recipients had ≥50% improvement in symptom score (on the modified Myelofibrosis Symptom Assessment Form version 2.0) versus 5.3% for placebo (p < 0.0001). Ruxolitinib recipients also showed improvement in parameters of quality of life. PMID:21919691

  18. Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients with Myelofibrosis With Prior exposure to JAK1/2 Inhibitors

    PubMed Central

    Shanavas, Mohamed; Popat, Uday; Michaelis, Laura C; Fauble, Veena; McLornan, Donal; Klisovic, Rebecca; Mascarenhas, John; Tamari, Roni; Arcasoy, Murat O; Davies, James; Gergis, Usama; Ukaegbu, Oluchi C; Kamble, Rammurti T; Storring, John M; Majhail, Navneet S; Romee, Rizwan; Verstovsek, Srdan; Pagliuca, Antonio; Vasu, Sumithira; Ernst, Brenda; Atenafu, Eshetu G; Hanif, Ahmad; Champlin, Richard; Hari, Paremeswaran; Gupta, Vikas

    2016-01-01

    The impact of JAK1/2 inhibitor therapy prior to allogeneic hematopoietic cell transplantation (HCT) has not been studied in a large cohort in myelofibrosis (MF). In this retrospective multicenter study, we analyzed outcomes of patients who underwent HCT for MF with prior exposure to JAK1/2 inhibitors. One hundred consecutive patients from participating centers were analyzed, and based on clinical status and response to JAK1/2 inhibitors at the time of HCT, patients were stratified into five groups: (a) clinical improvement (n=23), (b) stable disease (n=31), (c) new cytopenia/increasing blasts/intolerance (n=15), (d) progressive disease: splenomegaly (n=18), and (e) progressive disease: leukemic transformation (LT) (n=13). Overall survival (OS) at two years was 61% (95%CI, 49–71). This was 91% (95% CI, 69–98) for those who experienced clinical improvement, and 32% (95% CI, 8–59) for those who developed LT on JAK1/2 inhibitors. In multivariable analysis, response to JAK1/2 inhibitors (p=0.03), DIPSS score (p=0.003), and donor type (p=0.006) were independent predictors of survival. Among the 66 patients who remained on JAK1/2 inhibitors until stopped for HCT, two patients developed serious adverse events necessitating delaying of HCT, and another 8 patients had symptoms with lesser severity. Adverse events were more common in patients who started tapering or abruptly stopped their regular dose ≥6 days prior to conditioning therapy. We conclude that prior exposure to JAK1/2 inhibitors did not adversely affect post-transplant outcomes. Our data suggest that JAK1/2 inhibitors should be continued near to the start of conditioning therapy. The favorable outcomes of patients who experienced clinical improvement with JAK1/2 inhibitor therapy prior to HCT were particularly encouraging, and need further prospective validation. PMID:26493563

  19. Ferrokinetic study of splenic erythropoiesis: Relationships among clinical diagnosis, myelofibrosis, splenomegaly, and extramedullary erythropoiesis

    SciTech Connect

    Beguin, Y.; Fillet, G.; Bury, J.; Fairon, Y. )

    1989-10-01

    Splenic erythropoiesis was demonstrated by surface counting of {sup 59}Fe in 129 of 1,350 ferrokinetic studies performed over a 15 year period. These 129 studies were carried out in 108 patients, including 40 with chronic myelogenous leukemia (CML), 24 with agnogenic myeloid metaplasia (AMM), 18 with polycythemia vera (PV), six with a myelodysplastic syndrome, five with acute leukemia, three with prostate or breast carcinoma, two each with aplastic anemia or Hodgkin's disease, and one each with idiopathic thrombocythemia, multiple myeloma, chronic renal failure, or treated hypopituitarism. Splenomegaly was present in 83% of the studies and hepatomegaly in 72%. Grade II-III myelofibrosis was demonstrated in 62% of the cases. Hepatic erythropoiesis was present in 77% of the studies (only 38% in PV), and marrow erythropoiesis was undetectable in 33%. Total erythropoiesis was about twice normal (range 0.2 to 8 times normal) but was ineffective to varying degrees in 86% of the studies. Relationships between organomegaly, myelofibrosis, and extramedullary erythropoiesis, as well as differences among clinical disorders, are discussed. Differences observed between CML in chronic or blastic phase suggested that the erythroid cell line was involved in the proliferative process. It is concluded that splenic erythropoiesis (1) is encountered in a variety of clinical conditions; (2) is not necessarily associated with splenomegaly or myelofibrosis, even in the myeloproliferative disorders; (3) is part of a predominantly extramedullary (in the liver as well as in the spleen), expanded, and largely inefficient total erythropoiesis; and (4) can be evaluated in a semiquantitative manner by surface counting.

  20. Mayor Erythropoietic Response after Deferasirox Treatment in a Transfusion-Dependent Anemic Patient with Primary Myelofibrosis

    PubMed Central

    Lisette, Del Corso; Enrico, Balleari; Eleonora, Arboscello; Riccardo, Ghio; Manlio, Mencoboni; Omar, Racchi

    2013-01-01

    Primary myelofibrosis (PMF) is a myeloproliferative neoplasm frequently complicated by transfusion dependent anemia. Both anemia and transfusion-dependence are associated with a poor outcome, at least in part because of toxic effects of iron overload (IOL). Iron-chelating therapy (ICT) is increasingly used in order to prevent IOL in this setting. Here, we describe the case of a 73-year-old man affected by PMF and severe transfusion-dependent anemia who experienced a dramatic erythroid response after being treated with deferasirox to prevent IOL. PMID:24307957

  1. Mayor erythropoietic response after deferasirox treatment in a transfusion-dependent anemic patient with primary myelofibrosis.

    PubMed

    Lisette, Del Corso; Enrico, Balleari; Eleonora, Arboscello; Riccardo, Ghio; Manlio, Mencoboni; Omar, Racchi

    2013-01-01

    Primary myelofibrosis (PMF) is a myeloproliferative neoplasm frequently complicated by transfusion dependent anemia. Both anemia and transfusion-dependence are associated with a poor outcome, at least in part because of toxic effects of iron overload (IOL). Iron-chelating therapy (ICT) is increasingly used in order to prevent IOL in this setting. Here, we describe the case of a 73-year-old man affected by PMF and severe transfusion-dependent anemia who experienced a dramatic erythroid response after being treated with deferasirox to prevent IOL.

  2. Discrepancy in Diagnosis of Primary Myelofibrosis between Referral and Tertiary Care Centers

    PubMed Central

    Yi, Cecilia Arana; Jeyakumar, Ghayathri; Medina, Pedro; Cortes, Jorge; Pierce, Sherry; Bueso-Ramos, Carlos; Kantarjian, Hagop; Verstovsek, Srdan

    2015-01-01

    Primary myelofibrosis (PMF) is myeloproliferative neoplasm whose diagnosis is based on a combination of clinical and pathology criteria. We evaluated 560 consecutive patients who were diagnosed with PMF upon a referral to our center and evaluated the frequency of and reasons for diagnostic discordance. Discordance in the diagnosis was found in 70 (12.5%) patients. Discordant cases had a significantly lower grade of bone marrow fibrosis (grade 0–1), more likely to be JAK2V617F-mutation negative, and have no peripheral blood blasts, possibly explaining the difficulty in making a proper diagnosis and underscoring the need for a complete evaluation at a tertiary center. PMID:24284333

  3. European Bone Marrow Working Group trial on reproducibility of World Health Organization criteria to discriminate essential thrombocythemia from prefibrotic primary myelofibrosis

    PubMed Central

    Buhr, Thomas; Hebeda, Konnie; Kaloutsi, Vassiliki; Porwit, Anna; Van der Walt, Jon; Kreipe, Hans

    2012-01-01

    Background The World Health Organization classification of myeloproliferative neoplasms discriminates between essential thrombocythemia and the prefibrotic phase of primary myelofibrosis. This discrimination is clinically relevant because essential thrombocythemia is associated with a favorable prognosis whereas patients with primary myelofibrosis have a higher risk of progression to myelofibrosis or blast crisis. Design and Methods To assess the reproducibility of the classification, six hematopathologists from five European countries re-classified 102 non-fibrotic bone marrow trephines, obtained because of sustained thrombocytosis. Results Consensus on histological classification defined as at least four identical diagnoses occurred for 63% of the samples. Inter-observer agreement showed low to moderate kappa values (0.28 to 0.57, average 0.41). The percentage of unclassifiable myeloproliferative neoplasms rose from 2% to 23% when minor criteria for primary myelofibrosis were taken into account. In contrast, the frequency of primary myelofibrosis dropped from 23% to 7%, indicating that the majority of patients with a histological diagnosis of primary myelofibrosis did not fulfill the complete criteria for this disease. Thus, over 50% of cases in this series either could not be reproducibly classified or fell into the category of unclassifiable myeloproliferative neoplasms. Conclusions World Health Organization criteria for discrimination of essential thrombocythemia from prefibrotic primary myelofibrosis are poorly to only moderately reproducible and lead to a higher proportion of non-classifiable myeloproliferative neoplasms than histology alone. PMID:22058215

  4. A multinational, open-label, phase 2 study of ruxolitinib in Asian patients with myelofibrosis: Japanese subset analysis.

    PubMed

    Oritani, Kenji; Okamoto, Shinichiro; Tauchi, Tetsuzo; Saito, Shigeki; Ohishi, Kohshi; Handa, Hiroshi; Takenaka, Katsuto; Gopalakrishna, Prashanth; Amagasaki, Taro; Ito, Kazuo; Akashi, Koichi

    2015-03-01

    Ruxolitinib is a potent Janus kinase (JAK) 1/JAK2 inhibitor that has demonstrated rapid and durable improvements in splenomegaly and symptoms and a survival benefit in 2 phase 3 trials in patients with myelofibrosis. Ruxolitinib was well tolerated and effectively reduced splenomegaly and symptom burden in Asian patients with myelofibrosis in the Asian multinational, phase 2 Study A2202. We present a subset analysis of Japanese patients (n = 30) in Study A2202. At data cutoff, 22 patients were ongoing; 8 discontinued, mainly due to adverse events (n = 4). At week 24, 33 % of patients achieved ≥35 % reduction from baseline in spleen volume; 56.0 % achieved ≥50 % reduction from baseline in total symptom score, as measured by the 7-day Myelofibrosis Symptom Assessment Form v2.0. The most common adverse events were anemia (63 %), thrombocytopenia (40 %), nasopharyngitis (37 %), decreased platelet counts (30 %), and diarrhea (30 %). Dose reductions or interruptions due to hemoglobin decreases were more frequent in Japanese patients; no loss of efficacy and no discontinuations due to hematologic abnormalities were observed. Ruxolitinib was well tolerated in Japanese patients and provided substantial reductions in splenomegaly and myelofibrosis-related symptoms similar to those observed in the overall Asian population and phase 3 COMFORT studies.

  5. Acute myelofibrosis in a patient with diffuse large cell non Hodgkin's lymphoma and renal cancer.

    PubMed

    Mohren, Martin; Essbach, Uwe; Franke, Astrid; Klink, Anne; Maas, Christian; Markmann, Ilka; Pelz, Antje F; Jentsch-Ullrich, Kathleen

    2003-09-01

    Relapse after anthracycline based combination chemotherapy is frequently seen in patients with aggressive non Hodgkin's Lymphomas (NHL), whereas complications such as secondary leukemia or solid tumor rarely occur. We report a patient with diffuse large cell (DLC) NHL and concurrent renal cancer, who developed acute myelofibrosis (AMF) later in the course of her disease. This 60-year-old female patient presented with pancytopenia and a right sided renal mass. Diagnostic work up revealed severe bone marrow infiltration by DLC NHL and renal cancer T1N0M0G2. Cytogenetic and molecular evaluation of bone marow cells showed three distinct clones, (a normal 46XX karyotype, a ringed chromosome 7 and a third clone with an enlarged chromosome 2 as well as several fragments). The patient underwent nephrectomy and eventually received 6 cycles of CHOP 14 chemotherapy. Anemia persisted followed by severe granulocytopenia and thrombocytopenia 6 weeks later. Repeated bone marrow biopsy showed absence of lymphoma and/or cancer metastasis, but massive myelofibrosis with an increased number of atypical megakaryocytes. Considering the short clinical course and the absence of hepatosplenomegaly AMF was diagnosed. The concurrence of three distinctneoplasms within a short period of time as well as the complex cytogenetic aberrations found in her bone marrow cells reflect a strong individual susceptibility to malignant disease in this patient.

  6. Bone-marrow imaging with indium-111 chloride in aplastic anemia and myelofibrosis: concise communication

    SciTech Connect

    Sayle, B.A.; Helmer, R.E.; Birdsong, B.A.; Balachandran, S.; Gardner, F.H.

    1982-02-01

    Twenty-nine patients with aplastic anemia and 11 patients with myelofibrosis were evaluated with indium-111 chloride bone-marrow imaging, ferrokinetics, and bone-marrow core biopsies. There was good correlation between the erythrocyte cellularity of the marrow and the In-111 bone-marrow scan grades in most patients. In some, the overall scan grade tended to underestimate the erythroid elements because the core biopsy had been taken from the area of the greatest radionuclide concentration on the scan. In patients with aplastic anemia, there was good correlation between the plasma iron clearance t1/2 and the scan grade. Less agreement was found in the comparison between the Fe-59 sacral and organ counts and the red-cell iron utilization. In patients with myelofibrosis, there was poor correlation between the surface counts over the sacrum and the red-cell iron utilization. Plasma iron clearances were abnormally short and were unrelated to the transferrin saturation levels. Eighteen patients were studied several times to evaluate their responses to steroid therapy. In all, there was good correlation between the bone-marrow imaging, the erythrocyte cellularity, ferrokinetics, and the patient's response to therapy. Indium-111 bone-marrow imaging is useful both in evaluating marrow erythroid activity and in following the response to therapy in patients with these diseases.

  7. Mesenchymal Cell Reprogramming in Experimental MPLW515L Mouse Model of Myelofibrosis

    PubMed Central

    Wei, Max; Ren, Xiubao; Shao, Zonghong; Zhang, Ling; Levine, Ross L.; Epling-Burnette, Pearlie K.

    2017-01-01

    Myelofibrosis is an indicator of poor prognosis in myeloproliferative neoplasms (MPNs), but the precise mechanism(s) contributing to extracellular matrix remodeling and collagen deposition in the bone marrow (BM) niche remains unanswered. In this study, we isolated mesenchymal stromal cells (MSCs) from mice transplanted with wild-type thrombopoietin receptor (MPLWT) and MPLW515L retroviral-transduced bone marrow. Using MSCs derived from MPLW515-transplant recipients, excessive collagen deposition was maintained in the absence of the virus and neoplastic hematopoietic cells suggested that the MSCs were reprogrammed in vivo. TGFβ production by malignant megakaryocytes plays a definitive role promoting myelofibrosis in MPNs. However, TGFβ was equally expressed by MSCs derived from MPLWT and MPLW515L expressing mice and the addition of neutralizing anti-TGFβ antibody only partially reduced collagen secretion in vitro. Interestingly, profibrotic MSCs displayed increased levels of pSmad3 and pSTAT3 suggesting that inflammatory mediators cooperating with the TGFβ-receptor signaling may maintain the aberrant phenotype ex vivo. FGFb is a known suppressor of TGFβ signaling. Reduced collagen deposition by FGFb-treated MSCs derived from MPLW515L mice suggests that the activating pathway is vulnerable to this suppressive mediator. Therefore, our findings have implications for the future investigation of therapies to reverse fibrosis in MPNs. PMID:28135282

  8. Inflammation as a Keystone of Bone Marrow Stroma Alterations in Primary Myelofibrosis

    PubMed Central

    Desterke, Christophe; Martinaud, Christophe; Ruzehaji, Nadira; Le Bousse-Kerdilès, Marie-Caroline

    2015-01-01

    Primary myelofibrosis (PMF) is a clonal myeloproliferative neoplasm where severity as well as treatment complexity is mainly attributed to a long lasting disease and presence of bone marrow stroma alterations as evidenced by myelofibrosis, neoangiogenesis, and osteosclerosis. While recent understanding of mutations role in hematopoietic cells provides an explanation for pathological myeloproliferation, functional involvement of stromal cells in the disease pathogenesis remains poorly understood. The current dogma is that stromal changes are secondary to the cytokine “storm” produced by the hematopoietic clone cells. However, despite therapies targeting the myeloproliferation-sustaining clones, PMF is still regarded as an incurable disease except for patients, who are successful recipients of allogeneic stem cell transplantation. Although the clinical benefits of these inhibitors have been correlated with a marked reduction in serum proinflammatory cytokines produced by the hematopoietic clones, further demonstrating the importance of inflammation in the pathological process, these treatments do not address the role of the altered bone marrow stroma in the pathological process. In this review, we propose hypotheses suggesting that the stroma is inflammatory-imprinted by clonal hematopoietic cells up to a point where it becomes “independent” of hematopoietic cell stimulation, resulting in an inflammatory vicious circle requiring combined stroma targeted therapies. PMID:26640324

  9. Ruxolitinib is effective in patients with intermediate-1 risk myelofibrosis: a summary of recent evidence.

    PubMed

    Harrison, Claire N; Talpaz, Moshe; Mead, Adam J

    2016-10-01

    Ruxolitinib is the only therapy with an approved indication for myelofibrosis (MF), a myeloproliferative neoplasm associated with progressive bone marrow fibrosis and extramedullary hematopoiesis. Although the pivotal phase 3 COMFORT studies included only patients with intermediate-2 or high-risk MF, the US indication includes all patients with intermediate- or high-risk disease. Data from recent nonrandomized studies confirm that the benefits of ruxolitinib established in the COMFORT studies in terms of spleen size reduction and symptom improvement also extend to patients with intermediate-1 risk MF, who tend to have less advanced disease than patients with higher-risk MF. Given the disease-modifying potential of ruxolitinib therapy, timely initiation of ruxolitinib therapy may not only improve patients' current clinical status but also lead to better long-term outcomes. The decision of whether or when to initiate ruxolitinib treatment should be based on the expected benefit-risk ratio for each patient, specifically considering potential adverse effects.

  10. Primary autoimmune myelofibrosis with severe thrombocytopenia mimicking immune thrombocytopenia: A case report

    PubMed Central

    Hua, Jian; Matayoshi, Shu; Uchida, Tomoyuki; Inoue, Morihiro; Hagihara, Masao

    2016-01-01

    Patients presenting with bone marrow fibrosis not accompanied by well-established autoimmune diseases, such as systemic lupus erythematosus, or malignant diseases, are considered to have primary autoimmune myelofibrosis (AIMF). Primary AIMF has been reported to follow a benign course and responds well to treatment with immunosuppressive agents. Immune thrombocytopenia (ITP) is also an autoimmune disorder characterized by antiplatelet-antibody-mediated thrombocytopenia in the absence of other causes of thrombocytopenia. We herein present a rare case of a female patient who was diagnosed with primary AIMF. The patient presented with severe thrombocytopenia, which was initially misdiagnosed as ITP. The symptoms of the disease resolved completely following steroid treatment. After withdrawal of the treatment at 1 year from the diagnosis, the bone marrow examination showed no evidence of bone marrow fibrosis or other abnormalities. To date, the patient has been followed up for 2 years without evidence of disease. PMID:28105358

  11. Janus kinase inhibition and its effect upon the therapeutic landscape for myelofibrosis: from palliation to cure?

    PubMed

    Harrison, Claire; Verstovsek, Srdan; McMullin, Mary F; Mesa, Ruben

    2012-05-01

    Following the discovery of the Janus kinase (JAK) 2 V617F mutation in 2005 the explosion of research and drug development activity has not only advanced our understanding of the pathogenesis of myeloproliferative neoplasms (MPNs) but also triggered debate about classification, allowed revised diagnostic and response criteria, provided a target for treatment and a mode of monitoring its success. These changes and the resultant clinical research are discussed in this article where we argue that discovery of the JAK2 V617F mutation has signalled the much delayed change in therapeutic paradigm for myelofibrosis and possibly other MPNs from palliation and allowing us to move closer to, but not yet attain, a cure.

  12. Ruxolitinib in myelofibrosis: to be or not to be an immune disruptor

    PubMed Central

    Manduzio, Palma

    2017-01-01

    Primary myelofibrosis (PMF) is a myeloproliferative neoplasm classified according to the 2016 revision of World Health Organization Classification of Tumors and Haematopoietic and Lymphoid Tissue. Ruxolitinib is an oral inhibitor of Janus kinase approved in the USA for the treatment of intermediate or high-risk PMF and approved in Europe for the treatment of splenomegaly and constitutional symptoms of the disease. More recently, case reports described serious opportunistic infections in this neoplasm treated with ruxolitinib. Research studies demonstrated the immunological derangement of this compound mainly based on T, dendritic, and natural killer cell defects. The purpose of this review of the literature was to analyze the relationship among ruxolitinib, immune system and bacterial, viral, fungal, and protozoan infections. A literature search was conducted using PubMed articles published between January 2010 and November 2016. The efficacy of drug in patients with PMF was demonstrated in two phase III studies, Controlled MyeloFibrosis Study with ORal Jak inhibitor Treatment (COMFORT-I and COMFORT-II). Grade 3 and 4 neutropenia were recognized in 7.1% and 2% of patients in the ruxolitinib and placebo arm of COMFORT-I. Grade 3 or 4 neutropenia or leukopenia were observed in 8.9% and 6.3% of ruxolitinib treated patients of 5-year follow-up of COMFORT-II. In addition, leukocyte subpopulations, lymphocyte functions, or antibody deficiency were not documented in either of the studies. The complex interactions between ruxolitinib, bone marrow, immune system, and infections in PMF need further investigation, robust data from a randomized clinical trial, registry, or large case-series. PMID:28243106

  13. Calreticulin mutants in mice induce an MPL-dependent thrombocytosis with frequent progression to myelofibrosis.

    PubMed

    Marty, Caroline; Pecquet, Christian; Nivarthi, Harini; El-Khoury, Mira; Chachoua, Ilyas; Tulliez, Micheline; Villeval, Jean-Luc; Raslova, Hana; Kralovics, Robert; Constantinescu, Stefan N; Plo, Isabelle; Vainchenker, William

    2016-03-10

    Frameshift mutations in the calreticulin (CALR) gene are seen in about 30% of essential thrombocythemia and myelofibrosis patients. To address the contribution of the CALR mutants to the pathogenesis of myeloproliferative neoplasms, we engrafted lethally irradiated recipient mice with bone marrow cells transduced with retroviruses expressing these mutants. In contrast to wild-type CALR, CALRdel52 (type I) and, to a lesser extent, CALRins5 (type II) induced thrombocytosis due to a megakaryocyte (MK) hyperplasia. Disease was transplantable into secondary recipients. After 6 months, CALRdel52-, in contrast to rare CALRins5-, transduced mice developed a myelofibrosis associated with a splenomegaly and a marked osteosclerosis. Monitoring of virus-transduced populations indicated that CALRdel52 leads to expansion at earlier stages of hematopoiesis than CALRins5. However, both mutants still specifically amplified the MK lineage and platelet production. Moreover, a mutant deleted of the entire exon 9 (CALRdelex9) did not induce a disease, suggesting that the oncogenic property of CALR mutants was related to the new C-terminus peptide. To understand how the CALR mutants target the MK lineage, we used a cell-line model and demonstrated that the CALR mutants, but not CALRdelex9, specifically activate the thrombopoietin (TPO) receptor (MPL) to induce constitutive activation of Janus kinase 2 and signal transducer and activator of transcription 5/3/1. We confirmed in c-mpl- and tpo-deficient mice that expression of Mpl, but not of Tpo, was essential for the CALR mutants to induce thrombocytosis in vivo, although Tpo contributes to disease penetrance. Thus, CALR mutants are sufficient to induce thrombocytosis through MPL activation.

  14. Cyclophosphamide and Busulfan Followed by Donor Stem Cell Transplant in Treating Patients With Myelofibrosis, Acute Myeloid Leukemia, or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2014-04-03

    Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Childhood Acute Myeloid Leukemia in Remission; Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Myelodysplastic Syndrome With Isolated Del(5q); Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Secondary Myelofibrosis; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  15. A phase 1/2, open-label study evaluating twice-daily administration of momelotinib in myelofibrosis

    PubMed Central

    Gupta, Vikas; Mesa, Ruben A.; Deininger, Michael W.N.; Rivera, Candido E.; Sirhan, Shireen; Brachmann, Carrie Baker; Collins, Helen; Kawashima, Jun; Xin, Yan; Verstovsek, Srdan

    2017-01-01

    Momelotinib, a small-molecule inhibitor of Janus kinase 1 and Janus kinase 2, has demonstrated efficacy in myelofibrosis patients with 300 mg, once-daily dosing. This open-label, non-randomized, phase 1/2 study evaluated the safety and therapeutic benefit of momelotinib with twice-daily dosing. A total of 61 subjects with primary myelofibrosis or post–polycythemia vera/post–essential thrombocythemia myelofibrosis with intermediate- or high-risk disease received momelotinib. A phase 1 dose escalation identified 200 mg twice daily as the optimal dose to be expanded in phase 2. The most frequent adverse events were diarrhea (45.9%), peripheral neuropathy (44.3%), thrombocytopenia (39.3%), and dizziness (36.1%), the latter primarily due to a first-dose effect. The response assessment according to the 2006 International Working Group criteria (≥8 weeks duration at any time point) demonstrated spleen response by palpation of 72% (36/50) and anemia response of 45% (18/40). Spleen response by magnetic resonance imaging obtained at 24 weeks was 45.8% (27/59) for all subjects and 54.0% (27/50) for those with palpable splenomegaly at baseline. The symptoms of myelofibrosis were improved in most subjects. Cytokine analysis showed a rapid decline in interleukin-6 with momelotinib treatment, and a slower reduction in other inflammatory cytokines. In the subgroup of subjects with the JAK2V617F mutation at baseline (n=41), momelotinib significantly reduced the allele burden by 21.1% (median) at 24 weeks. These results provide evidence of tolerability and a potential therapeutic activity of momelotinib for subjects that support further evaluation in ongoing, phase 3 randomized trials. (clinicaltrials. gov identifier:01423058). PMID:27634203

  16. An accurate, simple prognostic model consisting of age, JAK2, CALR, and MPL mutation status for patients with primary myelofibrosis

    PubMed Central

    Rozovski, Uri; Verstovsek, Srdan; Manshouri, Taghi; Dembitz, Vilma; Bozinovic, Ksenija; Newberry, Kate; Zhang, Ying; Bove, Joseph E.; Pierce, Sherry; Kantarjian, Hagop; Estrov, Zeev

    2017-01-01

    In most patients with primary myelofibrosis, one of three mutually exclusive somatic mutations is detected. In approximately 60% of patients, the Janus kinase 2 gene is mutated, in 20%, the calreticulin gene is mutated, and in 5%, the myeloproliferative leukemia virus gene is mutated. Although patients with mutated calreticulin or myeloproliferative leukemia genes have a favorable outcome, and those with none of these mutations have an unfavorable outcome, prognostication based on mutation status is challenging due to the heterogeneous survival of patients with mutated Janus kinase 2. To develop a prognostic model based on mutation status, we screened primary myelofibrosis patients seen at the MD Anderson Cancer Center, Houston, USA, between 2000 and 2013 for the presence of Janus kinase 2, calreticulin, and myeloproliferative leukemia mutations. Of 344 primary myelofibrosis patients, Janus kinase 2V617F was detected in 226 (66%), calreticulin mutation in 43 (12%), and myeloproliferative leukemia mutation in 16 (5%); 59 patients (17%) were triple-negatives. A 50% cut-off dichotomized Janus kinase 2-mutated patients into those with high Janus kinase 2V617F allele burden and favorable survival and those with low Janus kinase 2V617F allele burden and unfavorable survival. Patients with a favorable mutation status (high Janus kinase 2V617F allele burden/myeloproliferative leukemia/calreticulin mutation) and aged 65 years or under had a median survival of 126 months. Patients with one risk factor (low Janus kinase 2V617F allele burden/triple-negative or age >65 years) had an intermediate survival duration, and patients aged over 65 years with an adverse mutation status (low Janus kinase 2V617F allele burden or triple-negative) had a median survival of only 35 months. Our simple and easily applied age- and mutation status-based scoring system accurately predicted the survival of patients with primary myelofibrosis. PMID:27686378

  17. Expanding the SHOC2 Mutation Associated Phenotype of Noonan Syndrome with Loose Anagen Hair: Structural Brain Anomalies and Myelofibrosis

    PubMed Central

    Gripp, Karen W.; Zand, Dina J.; Demmer, Laurie; Anderson, Carol E.; Dobyns, William B.; Zackai, Elaine H.; Denenberg, Elizabeth; Jenny, Kim; Stabley, Deborah L.; Sol-Church, Katia

    2013-01-01

    Noonan syndrome is a heterogenous rasopathy typically presenting with short stature, characteristic facial features, cardiac abnormalities including pulmonic valve stenosis, ASD and hypertrophic cardiomyopathy (HCM), cryptorchidism, ectodermal abnormalities and learning differences. The phenotype is variable, and limited genotype phenotype correlation exists with SOS1 mutations often associated with normal cognition and stature, RAF1 mutations entailing a high HCM risk, and certain PTPN11 mutations predisposing to juvenile myelomonocytic leukemia. The recently identified SHOC2 mutation (p.Ser2Gly) causes Noonan syndrome with loose anagen hair. We report five patients with this mutation. All had skin hyperpigmentation, sparse light colored hair, increased fine wrinkles, ligamentous laxity, developmental delay and 4/4 had a structural cardiac anomaly. Hypotonia and macrocephaly occurred in 4/5 (80%); 3/5 (60%) had polyhydramnios, increased birth weight or required use of a feeding tube. Distinctive brain abnormalities included relative megalencephaly and enlarged subarachnoid spaces suggestive of benign external hydrocephalus, and a relatively small posterior fossa as indicated by a vertical tentorium. The combination of a large brain with a small posterior fossa likely resulted in the high rate of cerebellar tonsillar ectopia (3/4) (75%). Periventricular nodular heterotopia was seen in one patient with a thick and dysplastic corpus callosum. We report on the first hematologic neoplasm, myelofibrosis, in a 2-year-old patient with SHOC2 mutation. Myelofibrosis is exceedingly rare in children and young adults. The absence of a somatic JAK2 mutation, seen in the majority of patients with myelofibrosis, is noteworthy as it suggests that germline or somatic SHOC2 mutations are causally involved in myelofibrosis. PMID:23918763

  18. Expanding the SHOC2 mutation associated phenotype of Noonan syndrome with loose anagen hair: structural brain anomalies and myelofibrosis.

    PubMed

    Gripp, Karen W; Zand, Dina J; Demmer, Laurie; Anderson, Carol E; Dobyns, William B; Zackai, Elaine H; Denenberg, Elizabeth; Jenny, Kim; Stabley, Deborah L; Sol-Church, Katia

    2013-10-01

    Noonan syndrome is a heterogenous rasopathy typically presenting with short stature, characteristic facial features, cardiac abnormalities including pulmonic valve stenosis, ASD and hypertrophic cardiomyopathy (HCM), cryptorchidism, ectodermal abnormalities, and learning differences. The phenotype is variable, and limited genotype phenotype correlation exists with SOS1 mutations often associated with normal cognition and stature, RAF1 mutations entailing a high HCM risk, and certain PTPN11 mutations predisposing to juvenile myelomonocytic leukemia. The recently identified SHOC2 mutation (p.Ser2Gly) causes Noonan syndrome with loose anagen hair. We report five patients with this mutation. All had skin hyperpigmentation, sparse light colored hair, increased fine wrinkles, ligamentous laxity, developmental delay, and 4/4 had a structural cardiac anomaly. Hypotonia and macrocephaly occurred in 4/5 (80%); 3/5 (60%) had polyhydramnios, increased birth weight or required use of a feeding tube. Distinctive brain abnormalities included relative megalencephaly and enlarged subarachnoid spaces suggestive of benign external hydrocephalus, and a relatively small posterior fossa as indicated by a vertical tentorium. The combination of a large brain with a small posterior fossa likely resulted in the high rate of cerebellar tonsillar ectopia (3/4; 75%). Periventricular nodular heterotopia was seen in one patient with a thick and dysplastic corpus callosum. We report on the first hematologic neoplasm, myelofibrosis, in a 2-year-old patient with SHOC2 mutation. Myelofibrosis is exceedingly rare in children and young adults. The absence of a somatic JAK2 mutation, seen in the majority of patients with myelofibrosis, is noteworthy as it suggests that germline or somatic SHOC2 mutations are causally involved in myelofibrosis.

  19. Primary Myelofibrosis

    MedlinePlus

    ... Myeloproliferative Neoplasms Treatment Myelodysplastic/ Myeloproliferative Neoplasms Treatment Chronic Myeloproliferative Neoplasms Treatment (PDQ®)–Patient Version General Information About Chronic ...

  20. The Small Molecule Inhibitor G6 Significantly Reduces Bone Marrow Fibrosis and the Mutant Burden in a Mouse Model of Jak2-Mediated Myelofibrosis

    PubMed Central

    Kirabo, Annet; Park, Sung O.; Wamsley, Heather L.; Gali, Meghanath; Baskin, Rebekah; Reinhard, Mary K.; Zhao, Zhizhuang J.; Bisht, Kirpal S.; Keserű, György M.; Cogle, Christopher R.; Sayeski, Peter P.

    2013-01-01

    Philadelphia chromosome–negative myeloproliferative neoplasms, including polycythemia vera, essential thrombocytosis, and myelofibrosis, are disorders characterized by abnormal hematopoiesis. Among these myeloproliferative neoplasms, myelofibrosis has the most unfavorable prognosis. Furthermore, currently available therapies for myelofibrosis have little to no efficacy in the bone marrow and hence, are palliative. We recently developed a Janus kinase 2 (Jak2) small molecule inhibitor called G6 and found that it exhibits marked efficacy in a xenograft model of Jak2-V617F–mediated hyperplasia and a transgenic mouse model of Jak2-V617F–mediated polycythemia vera/essential thrombocytosis. However, its efficacy in Jak2-mediated myelofibrosis has not previously been examined. Here, we hypothesized that G6 would be efficacious in Jak2-V617F–mediated myelofibrosis. To test this, mice expressing the human Jak2-V617F cDNA under the control of the vav promoter were administered G6 or vehicle control solution, and efficacy was determined by measuring parameters within the peripheral blood, liver, spleen, and bone marrow. We found that G6 significantly reduced extramedullary hematopoiesis in the liver and splenomegaly. In the bone marrow, G6 significantly reduced pathogenic Jak/STAT signaling by 53%, megakaryocytic hyperplasia by 70%, and the Jak2 mutant burden by 68%. Furthermore, G6 significantly improved the myeloid to erythroid ratio and significantly reversed the myelofibrosis. Collectively, these results indicate that G6 is efficacious in Jak2-V617F–mediated myelofibrosis, and given its bone marrow efficacy, it may alter the natural history of this disease. PMID:22796437

  1. CXCR4-independent rescue of the myeloproliferative defect of the Gata1low myelofibrosis mouse model by Aplidin.

    PubMed

    Verrucci, Maria; Pancrazzi, Alessandro; Aracil, Miguel; Martelli, Fabrizio; Guglielmelli, Paola; Zingariello, Maria; Ghinassi, Barbara; D'Amore, Emanuela; Jimeno, José; Vannucchi, Alessandro M; Migliaccio, Anna Rita

    2010-11-01

    The discovery of JAK2 mutations in Philadelphia-negative myeloproliferative neoplasms has prompted investigators to evaluate mutation-targeted treatments to restore hematopoietic cell functions in these diseases. However, the results of the first clinical trials with JAK2 inhibitors are not as promising as expected, prompting a search for additional drugable targets to treat these disorders. In this paper, we used the hypomorphic Gata1(low) mouse model of primary myelofibrosis (PMF), the most severe of these neoplasms, to test the hypothesis that defective marrow hemopoiesis and development of extramedullary hematopoiesis in myelofibrosis is due to insufficient p27(Kip1) activity and is treatable by Aplidin, a cyclic depsipeptide that activates p27(Kip1) in several cancer cells. Aplidin restored expression of Gata1 and p27(Kip1) in Gata1(low) hematopoietic cells, proliferation of marrow progenitor cells in vitro and maturation of megakaryocytes in vivo (reducing TGF-beta/VEGF levels released in the microenvironment by immature Gata1(low) megakaryocytes). Microvessel density, fibrosis, bone growth, and marrow cellularity were normal in Aplidin-treated mice and extramedullary hematopoiesis did not develop in liver although CXCR4 expression in Gata1(low) progenitor cells remained low. These results indicate that Aplidin effectively alters the natural history of myelofibrosis in Gata1(low) mice and suggest this drug as candidate for clinical evaluation in PMF.

  2. Does primary myelofibrosis involve a defective stem cell niche? From concept to evidence.

    PubMed

    Lataillade, Jean-Jacques; Pierre-Louis, Olivier; Hasselbalch, Hans Carl; Uzan, Georges; Jasmin, Claude; Martyré, Marie-Claire; Le Bousse-Kerdilès, Marie-Caroline

    2008-10-15

    Primary myelofibrosis (PMF) is the rarest and the most severe Philadelphia-negative chronic myeloproliferative syndrome. By associating a clonal proliferation and a mobilization of hematopoietic stem cells from bone marrow to spleen with profound alterations of the stroma, PMF is a remarkable model in which deregulation of the stem cell niche is of utmost importance for the disease development. This paper reviews key data suggesting that an imbalance between endosteal and vascular niches participates in the development of clonal stem cell proliferation. Mechanisms by which bone marrow niches are altered with ensuing mobilization and homing of neoplastic hematopoietic stem cells in new or reinitialized niches in the spleen and liver are examined. Differences between signals delivered by both endosteal and vascular niches in the bone marrow and spleen of patients as well as the responsiveness of PMF stem cells to their specific signals are discussed. A proposal for integrating a potential role for the JAK2 mutation in their altered sensitivity is made. A better understanding of the cross talk between stem cells and their niche should imply new therapeutic strategies targeting not only intrinsic defects in stem cell signaling but also regulatory hematopoietic niche-derived signals and, consequently, stem cell proliferation.

  3. Pros and cons of splenectomy in patients with myelofibrosis undergoing stem cell transplantation.

    PubMed

    Li, Z; Deeg, H J

    2001-03-01

    During fetal development, the spleen is a major hemopoietic organ. In the adult human, this task is relinquished to the bone marrow. However, under the stress of certain pathologic conditions, extramedullary hemopoiesis may again occur in the spleen. This is especially true for diseases of the marrow, in particular, myeloproliferative disorders such as agnogenic myeloid metaplasia, which is associated with severe fibrosis of the marrow space. At the same time, the spleen sequesters blood cells and contributes to peripheral blood cytopenias, which may improve following splenectomy. However, success is unpredictable, and the operative mortality of splenectomy is on the order of 10%. As a growing number of patients undergo hemopoietic stem cell transplantation as definitive therapy for myelofibrosis, the decision on splenectomy has additional ramifications since the spleen plays an important role in the kinetics of engraftment of donor cells and in immune reconstitution. We conclude from our analysis of available information that the benefit of splenectomy is difficult to predict, although after transplantation splenectomized patients have faster hemopoietic recovery. It appears that the most important indication for splenectomy in these patients is the relief of symptoms from massive spleen enlargement.

  4. Identification of 'short-lived' and 'long-lived' patients at presentation of idiopathic myelofibrosis.

    PubMed

    Cervantes, F; Pereira, A; Esteve, J; Rafel, M; Cobo, F; Rozman, C; Montserrat, E

    1997-06-01

    To contribute to a better knowledge of the prognosis of idiopathic myelofibrosis (IM), the prognostic value of the presenting features in 106 patients diagnosed with IM at a single institution during a 21-year period was retrospectively analysed. Median survival was 59.4 months (95% CI 40.7-75.4). Using univariate analysis, age > 64 years, constitutional symptoms (fever, night sweats, weight loss), Hb < 10 g/dl, circulating blasts (> or= 1%), and serum LDH > 3 times upper normal level were associated with a significantly shorter survival; male sex, platelet count < 100 x 10(9)/l, blood percentage of immature granulocytes (excluding blasts), low cholesterol levels and advanced marrow histological stage had borderline significance. Using multivariate study, only age > 64 years, constitutional symptoms, Hb < 10 g/dl, and circulating blasts retained their prognostic relevance. The latter three variables confirmed their predictive value in patients above and below the series median age, and were able to identify two groups of patients: a low-risk group of 67 patients with none or one bad prognostic factor, in whom IM had an indolent course (median survival 98.8 months, 95% CI 68.7-127.6), and a high-risk group, including 39 patients with two or three factors, with a more aggressive disease (median survival 20.6 months, 95% CI 10-28.2). Finally, the application of two recently proposed scoring systems (in which three prognostic groups are considered) was unable to separate intermediate- from high-risk patients.

  5. The role of zinc protoporphyrin measurement in the differentiation between primary myelofibrosis and essential thrombocythaemia.

    PubMed

    Metzgeroth, Georgia; Kanders, Eva-Maria; Erben, Philipp; Hofmann, Wolf-Karsten; Hastka, Jan

    2011-04-01

    The differentiation between primary myelofibrosis (PMF) and essential thrombocythaemia (ET) may be difficult especially in early-stage disease. In PMF, increased levels of inflammatory cytokines induce impaired iron utilisation and disturbed erythropoiesis. In conditions with impaired iron support to erythropoiesis, zinc protoporphyrin (ZPP) is produced instead of heme. Here, we investigate whether ZPP concentration can be useful in the differentiation between PMF and ET. Seventy newly diagnosed patients (PMF, n=24; ET, n=46) were analysed. Intraerythrocytic ZPP concentration (normal≤40 μmol/mol heme) was measured by an Aviv front-face haematofluorometer. In PMF, ZPP concentrations were significantly increased when compared to ET (99±37 μmol/mol heme vs. 36±13 μmol/mol heme, p<0.0001). There was also a significant difference between early-stage PMF and advanced disease (77±30 μmol/mol heme vs. 122±31 μmol/mol heme, p=0.003). ZPP>76 μmol/mol heme as observed in 71% of PMF patients were not seen in ET. In PMF patients responding to immunosuppressive treatment (n=4), the increase in haemoglobin was accompanied by declining ZPP. In summary, by detecting the disturbed iron metabolism common in PMF, ZPP may assist in the differentiation between PMF and ET. Concentrations>60 μmol/mol heme are unlikely in ET if iron deficiency is excluded. ZPP determination is also useful for monitoring the effect of therapy in PMF.

  6. Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis

    PubMed Central

    Rumi, Elisa; Pietra, Daniela; Pascutto, Cristiana; Guglielmelli, Paola; Martínez-Trillos, Alejandra; Casetti, Ilaria; Colomer, Dolors; Pieri, Lisa; Pratcorona, Marta; Rotunno, Giada; Sant’Antonio, Emanuela; Bellini, Marta; Cavalloni, Chiara; Mannarelli, Carmela; Milanesi, Chiara; Boveri, Emanuela; Ferretti, Virginia; Astori, Cesare; Rosti, Vittorio; Cervantes, Francisco; Barosi, Giovanni; Vannucchi, Alessandro M.

    2014-01-01

    We studied the impact of driver mutations of JAK2, CALR, (calreticulin gene) or MPL on clinical course, leukemic transformation, and survival of patients with primary myelofibrosis (PMF). Of the 617 subjects studied, 399 (64.7%) carried JAK2 (V617F), 140 (22.7%) had a CALR exon 9 indel, 25 (4.0%) carried an MPL (W515) mutation, and 53 (8.6%) had nonmutated JAK2, CALR, and MPL (so-called triple-negative PMF). Patients with CALR mutation had a lower risk of developing anemia, thrombocytopenia, and marked leukocytosis compared with other subtypes. They also had a lower risk of thrombosis compared with patients carrying JAK2 (V617F). At the opposite, triple-negative patients had higher incidence of leukemic transformation compared with either CALR-mutant or JAK2-mutant patients. Median overall survival was 17.7 years in CALR-mutant, 9.2 years in JAK2-mutant, 9.1 years in MPL-mutant, and 3.2 years in triple-negative patients. In multivariate analysis corrected for age, CALR-mutant patients had better overall survival than either JAK2-mutant or triple-negative patients. The impact of genetic lesions on survival was independent of current prognostic scoring systems. These observations indicate that driver mutations define distinct disease entities within PMF. Accounting for them is not only relevant to clinical decision-making, but should also be considered in designing clinical trials. PMID:24986690

  7. Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis.

    PubMed

    Rumi, Elisa; Pietra, Daniela; Pascutto, Cristiana; Guglielmelli, Paola; Martínez-Trillos, Alejandra; Casetti, Ilaria; Colomer, Dolors; Pieri, Lisa; Pratcorona, Marta; Rotunno, Giada; Sant'Antonio, Emanuela; Bellini, Marta; Cavalloni, Chiara; Mannarelli, Carmela; Milanesi, Chiara; Boveri, Emanuela; Ferretti, Virginia; Astori, Cesare; Rosti, Vittorio; Cervantes, Francisco; Barosi, Giovanni; Vannucchi, Alessandro M; Cazzola, Mario

    2014-08-14

    We studied the impact of driver mutations of JAK2, CALR, (calreticulin gene) or MPL on clinical course, leukemic transformation, and survival of patients with primary myelofibrosis (PMF). Of the 617 subjects studied, 399 (64.7%) carried JAK2 (V617F), 140 (22.7%) had a CALR exon 9 indel, 25 (4.0%) carried an MPL (W515) mutation, and 53 (8.6%) had nonmutated JAK2, CALR, and MPL (so-called triple-negative PMF). Patients with CALR mutation had a lower risk of developing anemia, thrombocytopenia, and marked leukocytosis compared with other subtypes. They also had a lower risk of thrombosis compared with patients carrying JAK2 (V617F). At the opposite, triple-negative patients had higher incidence of leukemic transformation compared with either CALR-mutant or JAK2-mutant patients. Median overall survival was 17.7 years in CALR-mutant, 9.2 years in JAK2-mutant, 9.1 years in MPL-mutant, and 3.2 years in triple-negative patients. In multivariate analysis corrected for age, CALR-mutant patients had better overall survival than either JAK2-mutant or triple-negative patients. The impact of genetic lesions on survival was independent of current prognostic scoring systems. These observations indicate that driver mutations define distinct disease entities within PMF. Accounting for them is not only relevant to clinical decision-making, but should also be considered in designing clinical trials.

  8. Looking forward: novel therapeutic approaches in chronic and advanced phases of myelofibrosis.

    PubMed

    Mascarenhas, John

    2015-01-01

    Myelofibrosis (MF) is complex at the pathobiologic level and heterogeneous at the clinical level. The advances in molecular characterization of MF provide important insight into the mechanisms driving this chronic myeloid malignancy, refine risk stratification, offer novel therapeutic targets, and serve to measure therapeutic response. Although JAK2 inhibition has been the focus of laboratory and clinical efforts over the last decade, current experimental therapeutic approaches have broadened to include inhibitors of key alternative signaling pathways, epigenetic modulators, anti-fibrotics, and immunotherapies. Based on compelling preclinical rationale, a number of JAK2 inhibitor based combination therapies are now actively being evaluated in the clinic with the goal of disease course modification. The role and timing of hematopoietic stem cell transplant (HSCT) for MF has been challenged with the availability of commercial ruxolitinib and the plethora of experimental treatment options that exist. Integration of preconditioning JAK2 inhibition, reduced intensity conditioning regimens, and alternative donor sources are all being explored in an attempt to optimize this potentially curative modality. This review will summarize modern MF risk stratification, current clinical research approaches to chronic and advance phase MF focusing on novel agents alone and in combination, and update the reader on new directions in HSCT.

  9. Clinicopathologic characteristics of prefibrotic-early primary myelofibrosis in Chinese patients.

    PubMed

    Gong, Xubo; Lu, Xingguo; Xiao, Xibin; Wang, Weiqin; Yang, Jin; Fu, Yanbiao; Zheng, Yanbo; Tang, Qiusu; Zhang, Xiaohong

    2014-03-01

    The clinicopathologic features of patients with prefibrotic-early primary myelofibrosis (PEPMF) are still uncertain, and the characteristics of PEPMF in Asian patients are rarely reported. This study analyzed the clinicopathologic characteristics of 42 Chinese patients with PMF newly diagnosed according to the 2008 World Health Organization criteria. Some clinical and laboratory features of the patients differed significantly from those of the predominantly white patients in Western countries. Chinese patients with PEPMF were more often male (1.28:1) and younger, less likely to have higher median hemoglobin concentrations (126 g/L), less frequently had palpable spleens (35.7%), and had longer median times between prefibrotic-early and classical PEPMF (64 months). On bone marrow trephine sections, Chinese patients were more likely to have increased granulopoiesis (78.6%) and less frequently had balloon-like megakaryocytes (61.9%), giant and staghorn megakaryocytes (35.7%), or megakaryocytes with hyperchromatic and dysplastic nuclei (40.4%). In conclusion, some clinicopathologic characteristics of PEPMF in Chinese patients in China differ substantially from those seen in predominantly white patients in Western countries, and more clinicopathologic studies involving different ethnic populations and geographic regions of the world should help unfold the characteristics of this disease.

  10. Autoimmune myelofibrosis accompanied by Sjögren's syndrome in a 47, XXX/46, XX mosaic woman.

    PubMed

    Takahashi, Tohru

    2014-01-01

    This report describes a patient with autoimmune myelofibrosis accompanied by Sjögren's syndrome (SS). A 36-year-old woman was admitted due to petechiae, purpura, gingival bleeding, dyspnea on exertion, and a lack of concentration. She had pancytopenia and was diagnosed with SS. A bone marrow study showed hypercellular marrow with reticulin fibrosis. Lymphocytic infiltrates and aggregates composed of a mixture of T and B cells in the marrow were also observed. A chromosomal analysis of the marrow cells showed 47, XXX and an analysis of peripheral lymphocytes revealed 47, XXX/46, XX mosaic results. The patient's cytopenia resolved following treatment with oral prednisolone.

  11. Fatal hepatic failure associated with graft rejection following reduced-intensity stem-cell transplantation for chronic idiopathic myelofibrosis (CIMF).

    PubMed

    Miyakoshi, Shigesaburo; Kami, Masahiro; Kishi, Yukiko; Murashige, Naoko; Yuji, Koichiro; Kusumi, Eiji; Matsumura, Tomoko; Onishi, Yasushi; Kobayashi, Kazuhiko; Kim, Sung-Won; Hamaki, Tamae; Takaue, Yoichi; Taniguchi, Shuichi

    2004-12-01

    A 54-year-old man with chronic idiopathic myelofibrosis (CIMF) underwent RIST. His clinical course had been uneventful until day 60, when splenomegaly reappeared. Hepatic dysfunction developed on day 75. Recipient-type hematopoiesis increased to 51% on day 90. After rapid tapering of cyclosporin, serum levels of AST and ALP normalized in parallel with recovery of complete chimerism on day 134. Yet, jaundice progressed. He died of liver failure on day 176. Postmortem examination revealed neither GVHD nor VOD. Graft rejection following RIST for CIMF may lead to fatal hepatic damage through extramedullary hematopoiesis in the liver or cytokine-mediated immune dysregulations.

  12. An interesting case of pachydermoperiostosis with idiopathic myelofibrosis associated with monosomy 22.

    PubMed

    Arikan, Senay; Sen, Ilker; Bahceci, Mithat; Tuzcu, Alpaslan; Ayli, Meltem

    2009-08-01

    A 24-year-old man was referred to our clinic in August 2003 with complaints of weakness, dizziness, and bilateral knee pain of 3 years' duration. Bilateral digital clubbing had been found on routine physical examination during his military service 4 years earlier. There were no cardiorespiratory or abdominal symptoms. There was no compromise in the activities of everyday life. The patient was not a chronic smoker. In the family history of the patient, his brother had been diagnosed with pachydermoperiostosis in another center 2 years earlier, but did not return to the hospital for a follow-up investigation of myelofibrosis. On physical examination, the patient showed marked drumstick clubbing of the hands (Fig. 1), and a pale general appearance. The causes of digital clubbing are shown in Table 1 (Fawcett RS, Linford S, Stulberg DL. Nail abnormalities: clues to systemic disease. Am Fam Physician 2004; 69: 1417-1424). Deep nasolabial folds were seen on the face. Skin hypertrophy, cutis verticis gyrata, and seborrhea on the face were also observed. The patient also complained of hyperhidrosis. Examination of the cardiovascular system was normal. There was bilateral swelling of the ankle and knee (Fig. 2). Hepatosplenomegaly was found on abdominal examination. Investigations showed hypochromic microcytic anemia [hemoglobin, 8.58 g/dL (normal, 12.2-18.1 g/dL); hematocrit, 28.1% (normal, 37.7-53.7%); white blood cell count, 3430/mm(3) (normal, 4600-10,200/mm(3)); neutrophils, 2470/mm(3) (normal, 2000-6900/mm(3)); lymphocytes, 820/mm(3) (normal, 600-3400/mm(3)); platelets, 162,000/mm(3) (normal, 142,000-424,000 mm(3)); mean corpuscular volume, 73.7 fL (normal, 80-97 fL)]. Anisocytosis, poikilocytosis, microcytosis, and hypochromia were observed on peripheral blood examination, and the erythrocyte sedimentation rate was 37 mm/h. The serum C-reactive protein level was 50.1 mg/L (normal, 0-5 mg/L). Biochemical parameters, including serum calcium, phosphate, alkaline

  13. The role of growth differentiation factor 15 in the pathogenesis of primary myelofibrosis

    PubMed Central

    Uchiyama, Tatsuki; Kawabata, Hiroshi; Miura, Yasuo; Yoshioka, Satoshi; Iwasa, Masaki; Yao, Hisayuki; Sakamoto, Soichiro; Fujimoto, Masakazu; Haga, Hironori; Kadowaki, Norimitsu; Maekawa, Taira; Takaori-Kondo, Akifumi

    2015-01-01

    Growth differentiation factor 15 (GDF15) is a pleiotropic cytokine that belongs to the transforming growth factor-β superfamily. Elevated serum concentrations of this cytokine have been reported in patients with various malignancies. To assess the potential roles of GDF15 in hematologic malignancies, we measured its serum levels in patients with these diseases. We found that serum GDF15 levels were elevated in almost all these patients, particularly in patients with primary myelofibrosis (PMF). Immunohistochemical staining of bone marrow (BM) specimens revealed that GDF15 was strongly expressed by megakaryocytes, which may be sources of increased serum GDF15 in PMF patients. Therefore, we further assessed the contribution of GDF15 to the pathogenesis of PMF. Recombinant human (rh) GDF15 enhanced the growth of human BM mesenchymal stromal cells (BM-MSCs), and it enhanced the potential of these cells to support human hematopoietic progenitor cell growth in a co-culture system. rhGDF15 enhanced the growth of human primary fibroblasts, but it did not affect their expression of profibrotic genes. rhGDF15 induced osteoblastic differentiation of BM-MSCs in vitro, and pretreatment of BM-MSCs with rGDF15 enhanced the induction of bone formation in a xenograft mouse model. These results suggest that serum levels of GDF15 in PMF are elevated, that megakaryocytes are sources of this cytokine in BM, and that GDF15 may modulate the pathogenesis of PMF by enhancing proliferation and promoting osteogenic differentiation of BM-MSCs. PMID:26276681

  14. Initial (prefibrotic) stages of idiopathic (primary) myelofibrosis (IMF) - a clinicopathological study.

    PubMed

    Thiele, J; Kvasnicka, H M; Boeltken, B; Zankovich, R; Diehl, V; Fischer, R

    1999-11-01

    A clinicopathological follow-up study including sequential bone marrow biopsies was performed on 79 patients with idiopathic (primary) myelofibrosis (IMF) to characterize initial (prefibrotic) stages and to elucidate whether development of fibrosis was accompanied by corresponding clinical findings. For this purpose our cohort of patients was divided into two groups of which the first presented with the generally accepted signs and symptoms of IMF (group I; n = 60). Most patients of the second group (group II; n = 19) showed mild to moderate therapy-refractory anemia, minimal to slight splenomegaly and frequently thrombocytosis, but no bone marrow fibrosis at onset. Hematopoiesis was consistent with a striking hypercellularity in comparison to the age-related involution by adipose tissue, a conspicuous clustering and histotopographic dislocation of megakaryocytes, a neutrophil granulocytic proliferation and a reduction of erythropoietic islets with arrest of maturation. Most remarkable was the dysplastic cytology of megakaryocytes with a definitive deviation of differentiation resulting in bizarre forms. Follow-up examinations revealed that at later stages group II patients were not distinguishable from the first group with more advanced IMF. For this reason, these patients were regarded as presenting initial, prefibrotic IMF characterized by distinctive bone marrow features at the beginning. The prominent abnormalities of megakaryopoiesis together with the granulocytic proliferation were extremely helpful to differentiate prefibrotic IMF with accompanying thrombocythemia from essential thrombocythemia (ET). Dynamics of fiber progression were calculated by regarding increase in density per time. Speed of progression during the first year of observation proved to be significantly higher in group II patients with prefibrotic IMF in comparison to full-blown cases (group I). In conclusion, with respect to prospective clinical trials, diagnostic criteria for IMF should

  15. Critical appraisal of the role of ruxolitinib in myeloproliferative neoplasm-associated myelofibrosis

    PubMed Central

    Barosi, Giovanni; Rosti, Vittorio; Gale, Robert Peter

    2015-01-01

    The recent approval of molecular-targeted therapies for myeloproliferative neoplasm-associated myelofibrosis (MPN-MF) has dramatically changed its therapeutic landscape. Ruxolitinib, a JAK1/JAK2 tyrosine kinase inhibitor, is now widely used for first- and second-line therapy in persons with MPN-MF, especially those with disease-related splenomegaly, intermediate- or high-risk disease, and constitutional symptoms. The goal of this work is to critically analyze data supporting use of ruxolitinib in the clinical settings approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). We systematically reviewed the literature and analyzed the risk of biases in the two randomized studies (COMFORT I and COMFORT II) on which FDA and EMA approval was based. Our strategy was to apply the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach by evaluating five dimensions of evidence: (1) overall risk of bias, (2) imprecision, (3) inconsistency, (4) indirectness, and (5) publication bias. Based on these criteria, we downgraded the evidence from the COMFORT I and COMFORT II trials for performance, attrition, and publication bias. In the disease-associated splenomegaly sphere, we upgraded the quality of evidence because of large effect size but downgraded it because of comparator choice and outcome indirectness (quality of evidence, low). In the sphere of treating persons with intermediate- or high-risk disease, we downgraded the evidence because of imprecision in effect size measurement and population indirectness. In the sphere of disease-associated symptoms, we upgraded the evidence because of the large effect size, but downgraded it because of comparator indirectness (quality of evidence, moderate). In conclusion, using the GRADE technique, we identified factors affecting the quality of evidence that were otherwise unstated. Identifying and evaluating these factors should influence the confidence with which physicians

  16. Tie2 Expressing Monocytes in the Spleen of Patients with Primary Myelofibrosis

    PubMed Central

    Campanelli, Rita; Fois, Gabriela; Catarsi, Paolo; Poletto, Valentina; Villani, Laura; Erba, Benedetta Gaia; Maddaluno, Luigi; Jemos, Basilio; Salmoiraghi, Silvia; Guglielmelli, Paola; Abbonante, Vittorio; Di Buduo, Christian Andrea; Balduini, Alessandra; Iurlo, Alessandra; Barosi, Giovanni; Rosti, Vittorio; Massa, Margherita

    2016-01-01

    Primary myelofibrosis (PMF) is a Philadelphia-negative (Ph−) myeloproliferative disorder, showing abnormal CD34+ progenitor cell trafficking, splenomegaly, marrow fibrosis leading to extensive extramedullary haematopoiesis, and abnormal neoangiogenesis in either the bone marrow or the spleen. Monocytes expressing the angiopoietin-2 receptor (Tie2) have been shown to support abnormal angiogenic processes in solid tumors through a paracrine action that takes place in proximity to the vessels. In this study we investigated the frequency of Tie2 expressing monocytes in the spleen tissue samples of patients with PMF, and healthy subjects (CTRLs), and evaluated their possible role in favouring spleen angiogenesis. We show by confocal microscopy that in the spleen tissue of patients with PMF, but not of CTRLs, the most of the CD14+ cells are Tie2+ and are close to vessels; by flow cytometry, we found that Tie2 expressing monocytes were Tie2+CD14lowCD16brightCDL62−CCR2− (TEMs) and their frequency was higher (p = 0.008) in spleen tissue-derived mononuclear cells (MNCs) of patients with PMF than in spleen tissue-derived MNCs from CTRLs undergoing splenectomy for abdominal trauma. By in vitro angiogenesis assay we evidenced that conditioned medium of immunomagnetically selected spleen tissue derived CD14+ cells of patients with PMF induced a denser tube like net than that of CTRLs; in addition, CD14+Tie2+ cells sorted from spleen tissue derived single cell suspension of patients with PMF show a higher expression of genes involved in angiogenesis than that found in CTRLs. Our results document the enrichment of Tie2+ monocytes expressing angiogenic genes in the spleen of patients with PMF, suggesting a role for these cells in starting/maintaining the pathological angiogenesis in this organ. PMID:27281335

  17. Iron Chelation Therapy with Deferasirox in the Management of Iron Overload in Primary Myelofibrosis

    PubMed Central

    Elli, Elena Maria; Belotti, Angelo; Aroldi, Andrea; Parma, Matteo; Pioltelli, Pietro; Pogliani, Enrico Maria

    2014-01-01

    Deferasirox (DSX) is the principal option currently available for iron-chelation-therapy (ICT), principally in the management of myelodysplastic syndromes (MDS), while in primary myelofibrosis (PMF) the expertise is limited. We analyzed our experience in 10 PMF with transfusion-dependent anemia, treated with DSX from September 2010 to December 2013. The median dose tolerated of DSX was 750 mg/day (10 mg/kg/day), with 3 transient interruption of treatment for drug-related adverse events (AEs) and 3 definitive discontinuation for grade 3/4 AEs. According to IWG 2006 criteria, erythroid responses with DSX were observed in 4/10 patients (40%), 2 of them (20%) obtaining transfusion independence. Absolute changes in median serum ferritin levels (Delta ferritin) were greater in hematologic responder (HR) compared with non-responder (NR) patients, already at 6 months of ICT respect to baseline. Our preliminary data open new insights regarding the benefit of ICT not only in MDS, but also in PMF with the possibility to obtain an erythroid response, overall in 40 % of patients. HR patients receiving DSX seem to have a better survival and a lower incidence of leukemic transformation (PMF-BP). Delta ferritin evaluation at 6 months could represent a significant predictor for a different survival and PMF-BP. However, the tolerability of the drug seems to be lower compared to MDS, both in terms of lower median tolerated dose and for higher frequency of discontinuation for AEs. The biological mechanism of action of DSX in chronic myeloproliferative setting through an independent NF-κB inhibition could be involved, but further investigations are required. PMID:24959339

  18. A 7-Gene Signature Depicts the Biochemical Profile of Early Prefibrotic Myelofibrosis

    PubMed Central

    Skov, Vibe; Burton, Mark; Thomassen, Mads; Stauffer Larsen, Thomas; Riley, Caroline H.; Brinch Madelung, Ann; Kjær, Lasse; Bondo, Henrik; Stamp, Inger; Ehinger, Mats; Dahl-Sørensen, Rasmus; Brochmann, Nana; Nielsen, Karsten; Thiele, Jürgen; Jensen, Morten K.; Weis Bjerrum, Ole; Kruse, Torben A.; Hasselbalch, Hans Carl

    2016-01-01

    Recent studies have shown that a large proportion of patients classified as essential thrombocythemia (ET) actually have early primary prefibrotic myelofibrosis (prePMF), which implies an inferior prognosis as compared to patients being diagnosed with so-called genuine or true ET. According to the World Health Organization (WHO) 2008 classification, bone marrow histology is a major component in the distinction between these disease entities. However, the differential diagnosis between them may be challenging and several studies have not been able to distinguish between them. Most lately, it has been argued that simple blood tests, including the leukocyte count and plasma lactate dehydrogenase (LDH) may be useful tools to separate genuine ET from prePMF, the latter disease entity more often being featured by anemia, leukocytosis and elevated LDH. Whole blood gene expression profiling was performed in 17 and 9 patients diagnosed with ET and PMF, respectively. Using elevated LDH obtained at the time of diagnosis as a marker of prePMF, a 7-gene signature was identified which correctly predicted the prePMF group with a sensitivity of 100% and a specificity of 89%. The 7 genes included MPO, CEACAM8, CRISP3, MS4A3, CEACAM6, HEMGN, and MMP8, which are genes known to be involved in inflammation, cell adhesion, differentiation and proliferation. Evaluation of bone marrow biopsies and the 7-gene signature showed a concordance rate of 71%, 79%, 62%, and 38%. Our 7-gene signature may be a useful tool to differentiate between genuine ET and prePMF but needs to be validated in a larger cohort of “ET” patients. PMID:27579896

  19. Correlation of mutation profile and response in patients with myelofibrosis treated with ruxolitinib

    PubMed Central

    Patel, Keyur P.; Newberry, Kate J.; Luthra, Rajyalakshmi; Jabbour, Elias; Pierce, Sherry; Cortes, Jorge; Singh, Rajesh; Mehrotra, Meenakshi; Routbort, Mark J.; Luthra, Madan; Manshouri, Taghi; Santos, Fabio P.; Kantarjian, Hagop

    2015-01-01

    Although most patients with myelofibrosis (MF) derive benefit from ruxolitinib, some are refractory, have a suboptimal response, or quickly lose their response. To identify genes that may predict response to ruxolitinib, we performed targeted next-generation sequencing (NGS) of a panel of 28 genes recurrently mutated in hematologic malignancies in a cohort of patients with MF who were treated with ruxolitinib in a phase 1/2 study. We also tested for CALR deletions by standard polymerase chain reaction methods. Ninety-eight percent of patients had a mutation in ≥1 gene. Seventy-nine (82.1%) patients had the JAK2V617F mutation, 9 (9.5%) had CALR mutations (7 type 1, 2 type 2), 3 (3.1%) had MPL mutations, and 4 (4.2%) were negative for all 3. ASXL1/JAK2 and TET2/JAK2 were the most frequently comutated genes. Mutations in NRAS, KRAS, PTPN11, GATA2, TP53, and RUNX1 were found in <5% of patients. Spleen response (≥50% reduction in palpable spleen size) was inversely correlated with the number of mutations; patients with ≤2 mutations had ninefold higher odds of a spleen response than those with ≥3 mutations (odds ratio = 9.37; 95% confidence interval, 1.86-47.2). Patients with ≥3 mutations also had a shorter time to treatment discontinuation and shorter overall survival than those with fewer mutations. In multivariable analysis, only number of mutations and spleen response remained associated with time to treatment discontinuation. Patients with ≥3 mutations had the worst outcomes, suggesting that multigene profiling may be useful for therapeutic planning for MF. PMID:26124496

  20. CALR exon 9 mutations are somatically acquired events in familial cases of essential thrombocythemia or primary myelofibrosis.

    PubMed

    Rumi, Elisa; Harutyunyan, Ashot S; Pietra, Daniela; Milosevic, Jelena D; Casetti, Ilaria C; Bellini, Marta; Them, Nicole C C; Cavalloni, Chiara; Ferretti, Virginia V; Milanesi, Chiara; Berg, Tiina; Sant'Antonio, Emanuela; Boveri, Emanuela; Pascutto, Cristiana; Astori, Cesare; Kralovics, Robert; Cazzola, Mario

    2014-04-10

    Somatic mutations in the calreticulin (CALR) gene were recently discovered in patients with sporadic essential thrombocythemia (ET) and primary myelofibrosis (PMF) lacking JAK2 and MPL mutations. We studied CALR mutation status in familial cases of myeloproliferative neoplasm. In a cohort of 127 patients, CALR indels were identified in 6 of 55 (11%) subjects with ET and in 6 of 20 (30%) with PMF, whereas 52 cases of polycythemia vera had nonmutated CALR. All CALR mutations were somatic, found in granulocytes but not in T lymphocytes. Patients with CALR-mutated ET showed a higher platelet count (P = .017) and a lower cumulative incidence of thrombosis (P = .036) and of disease progression (P = .047) compared with those with JAK2 (V617F). In conclusion, a significant proportion of familial ET and PMF nonmutated for JAK2 carry a somatic mutation of CALR.

  1. [Review of evidence of thalidomide and lenalidomide in different hematological diseases: chronic lymphocytic leukemia, primary amyloidosis, myelofibrosis and syndrome myelodysplastic].

    PubMed

    Jiménez Lozano, I; Juárez Jiménez, J C

    2013-01-01

    Lenalidomide is an immunomodulatory drug approved by the AEMPS and the EMA, in combination with dexamethasone, for the treatment of multiple myeloma in adult patients who have received at least one prior therapy. Moreover, it has recently been approved for the treatment of patients with transfusion-dependent anaemia due to low- or intermediate-1-risk myelodysplastic syndromes associated with an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate. It has also shown to be active in other hematologic and no hematologic diseases. Growing evidence of its use entails a challenge when situating the drug in a cost-effective way to treat these diseases. On this article we review the available evidence on the use of lenalidomide in the second line treatment of patients with chronic lymphocytic leukemia, primary amyloidosis and primary myelofibrosis, and in the first line treatment of patients with myelodysplastic syndrome, and also the evidence of other immunomodulators. Different clinical practice guidelines and scientific evidence portals consider lenalidomide a valid alternative in the first-line treatment of patients with myelodysplastic syndromes, specially those with the deletion of 5q, and in second line for patients with chronic lymphocytic leukemia. However, the available evidence of lenalidomide in the treatment of patients with primary amyloidosis and primary myelofibrosis is limited, ant thus is not considered as the first choice treatment. In any case, the treatment of choice should consider the safety profile in each patient, the previous treatments that has received and the own therapeutic protocols of each center.

  2. Synergism between fibronectin and transforming growth factor-β1 in the production of substance P in monocytes of patients with myelofibrosis.

    PubMed

    Chang, Victor T; Yook, Clara; Rameshwar, Pranela

    2013-03-01

    Substance P (SP), also considered a proinflammatory cytokine, as well as others such as transforming growth factor-β1 (TGF-β1) and interleukin-1 (IL-1), and the extracellular matrix protein fibronectin (FN) have been associated with the pathophysiology of myelofibrosis. SP is encoded by the TAC1 gene. The relationships among SP, TGF-β1, IL-1 and FN are poorly understood. This study determined the mechanisms for concomitant production of IL-1, TGF-β1 and SP and also determined the synergistic role of FN in SP release. Enzyme-linked immunosorbent assay (ELISA) indicated increased levels of SP and TGF-β1 in the blood of patients with myelofibrosis. Monocytes, shown to be activated in patients with bone marrow (BM) fibrosis, expressed the TAC1 gene for SP release, in a nuclear factor-κB (NFκB)-dependent manner. Reporter gene assay with the 5' regulatory region of TAC1 indicated its expression by high levels of FN and TGF-β1. Immunohistochemical studies of paraffin-embedded BM biopsies from patients with myelofibrosis, and age-matched controls without fibrosis, indicated co-localization of SP and its receptor neurokinin-1 (NK1). In summary, myelofibrotic monocytes have autocrine loops that stimulate the release of SP and TGF-β1, and that are potentiated by fibronectin. The FN-mediated induction of SP in turn stimulates monocytes through autostimulation by NK1 receptors. These findings, combined with those of previous studies, demonstrate an adhesion-mediated NFκB/IL-1/TGF-β1 axis that can be initiated by increased FN in patients with myelofibrosis for the production of SP. These findings show how TGF-β1 and SP production are coupled, and suggest new therapeutic targets to reverse immune-mediated fibrosis.

  3. A phase I, open-label, dose-escalation, multicenter study of the JAK2 inhibitor NS-018 in patients with myelofibrosis

    PubMed Central

    Verstovsek, S; Talpaz, M; Ritchie, E; Wadleigh, M; Odenike, O; Jamieson, C; Stein, B; Uno, T; Mesa, R A

    2017-01-01

    NS-018 is a Janus-activated kinase 2 (JAK2)-selective inhibitor, targeting the JAK–signal transducer and activator of transcription (STAT) pathway that is deregulated in myelofibrosis. In this phase I, dose-escalation portion of a phase I/II study, patients with myelofibrosis received oral NS-018 in continuous 28-day cycles. The primary study objective was to evaluate safety, tolerability and clinically active dose of NS-018. Forty-eight patients were treated; 23 (48%) had previously received a JAK inhibitor (JAKi). The most common drug-related adverse events were thrombocytopenia (27%)/anemia (15%) for hematologic events, and dizziness (23%)/nausea (19%) for non-hematologic events. Once daily NS-018 at 300 mg was chosen as the phase II study dose based on improved tolerability compared with higher doses. A ⩾50% reduction in palpable spleen size was achieved in 56% of patients (47% of patients with prior JAKi treatment), and improvements were observed in myelofibrosis-associated symptoms. Bone marrow fibrosis grade (local assessment) improved from baseline in 11/30 evaluable patients (37%) after 3 cycles of NS-018. JAK2 allele burden was largely unchanged. Changes in cytokine/protein levels were noted after 4 weeks of treatment. NS-018 reached peak plasma concentration in 1–2 h and did not accumulate with multiple dosing. NS-018 will be assessed in patients with previous JAKi exposure in the phase II portion. PMID:27479177

  4. Medical complications, resource utilization and costs in patients with myelofibrosis by frequency of blood transfusion and iron chelation therapy.

    PubMed

    Vekeman, Francis; Cheng, Wendy Y; Sasane, Medha; Huynh, Lynn; Duh, Mei Sheng; Paley, Carole; Mesa, Ruben A

    2015-01-01

    Iron chelation therapies (ICTs) can help eliminate iron surplus in erythrocyte transfusion-dependent (TD) patients with myelofibrosis (MF). The study assessed adjusted incidence rate ratios (aIRRs) of MF-related complications and resource utilization (RU) and adjusted mean monthly inpatient cost differences in patients with TD MF treated with versus without ICT (ICT+ vs. ICT-) using data from two healthcare claims databases. Patients with ≥ 2 MF International Classification of Diseases, 9th Revision (ICD-9) diagnosis codes ≥ 30 days apart were included. Among 571 patients with TD MF, 103 (18%) were ICT+ and 468 (82%) were ICT-. ICT+ patients had lower rates of thrombocytopenia (aIRR: 0.55; p < 0.001), pancytopenia (0.53; p < 0.001), emergency room visits (0.84 [95% confidence interval: 0.74-0.96]) and inpatient stays (0.75 [0.64-0.87]), but higher rates of outpatient visits (1.21 [1.18-1.23]). Adjusted mean complication-related inpatient cost difference per month was lower in ICT+ patients (-$1804 [$570]; p = 0.004). ICT+ patients had significantly lower rates of acute care, but higher rates of outpatient care.

  5. Hematopoietic cell transplantation as curative therapy for patients with myelofibrosis: Long-term success in all age groups

    PubMed Central

    Deeg, H. Joachim; Bredeson, Christopher; Farnia, Stephanie; Ballen, Karen; Gupta, Vikas; Mesa, Ruben A.; Popat, Uday; Saber, Wael; Seftel, Matthew; Tamari, Roni; Pertersdorf, Effie

    2015-01-01

    Myeloproliferative neoplasms (MPN) are chronic marrow disorders with variable prognosis. Most patients with Polycythemia Vera, Essential Thrombocythemia or even Primary Myelofibrosis (PMF) are successfully managed by conservative strategies for years or even decades, and recent data suggest that even in patients with high-risk disease, in particular those with PMF, life expectancy can be extended by treatment with JAK2 inhibitors. However, none of those modalities are curative, and once marrow failure develops, the disease “accelerates” or transforms to acute leukemia, the only treatment option able to effectively treat and, in fact, cure MPN is allogeneic hematopoietic cell transplantation (HCT). Outcome is superior if HCT is performed before leukemic transformation occurs. Several reports document survival in unmaintained remission beyond 10 years. The most recent analyses show reduced regimen-related mortality (less than 10% or even 5% at day 100), and progressively improved survival with both HLA-identical sibling and unrelated donors. The development of low/reduced intensity conditioning regimens has contributed to the improved success rate and has allowed to successfully carry out HCT in patients in the 7th and even 8th decade of life. We propose, therefore, that HCT should be offered to fit patients in these age groups and should be covered by their respective insurance carriers. PMID:26371371

  6. Myeloproliferative neoplasms working group consensus recommendations for diagnosis and management of primary myelofibrosis, polycythemia vera, and essential thrombocythemia

    PubMed Central

    Agarwal, M. B.; Malhotra, Hemant; Chakrabarti, Prantar; Varma, Neelam; Mathews, Vikram; Bhattacharyya, Jina; Seth, Tulika; Gayathri, K.; Menon, Hari; Subramanian, P. G.; Sharma, Ajay; Bhattacharyya, Maitreyee; Mehta, Jay; Vaid, A. K.; Shah, Sandeep; Aggarwal, Shyam; Gogoi, P. K.; Nair, Reena; Agarwal, Usha; Varma, Subhash; Prasad, S. V. S. S.; Manipadam, Marie Therese

    2015-01-01

    According to the 2008 revision of the World Health Organization (WHO) classification of myeloid malignancies, philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPNs) include clonal, hematologic disorders such as polycythemia vera, primary myelofibrosis, and essential thrombocythemia.Recent years have witnessed major advances in the understanding of the molecular pathophysiology of these rare subgroups of chronic, myeloproliferative disorders. Identification of somatic mutations in genes associated with pathogenesis and evolution of these myeloproliferative conditions (Janus Kinase 2; myeloproliferative leukemia virus gene; calreticulin) led to substantial changes in the international guidelines for diagnosis and treatment of Ph-negative MPN during the last few years.The MPN-Working Group (MPN-WG), a panel of hematologists with expertise in MPN diagnosis and treatment from various parts of India, examined applicability of this latest clinical and scientific evidence in the context of hematology practice in India.This manuscript summarizes the consensus recommendations formulated by the MPN-WG that can be followed as a guideline for management of patients with Ph-negative MPN in the context of clinical practice in India. PMID:25810569

  7. Clonal Evolution Revealed by Whole Genome Sequencing in a Case of Primary Myelofibrosis Transformed to Secondary Acute Myeloid Leukemia

    PubMed Central

    Engle, Elizabeth K.; Fisher, Daniel A.C.; Miller, Christopher A.; McLellan, Michael D.; Fulton, Robert S.; Moore, Deborah M.; Wilson, Richard K.; Ley, Timothy J.; Oh, Stephen T.

    2014-01-01

    Clonal architecture in myeloproliferative neoplasms (MPNs) is poorly understood. Here we report genomic analyses of a patient with primary myelofibrosis (PMF) transformed to secondary acute myeloid leukemia (sAML). Whole genome sequencing (WGS) was performed on PMF and sAML diagnosis samples, with skin included as a germline surrogate. Deep sequencing validation was performed on the WGS samples and an additional sample obtained during sAML remission/relapsed PMF. Clustering analysis of 649 validated somatic single nucleotide variants revealed four distinct clonal groups, each including putative driver mutations. The first group (including JAK2 and U2AF1), representing the founding clone, included mutations with high frequency at all three disease stages. The second clonal group (including MYB) was present only in PMF, suggesting the presence of a clone that was dispensable for transformation. The third group (including ASXL1) contained mutations with low frequency in PMF and high frequency in subsequent samples, indicating evolution of the dominant clone with disease progression. The fourth clonal group (including IDH1 and RUNX1) was acquired at sAML transformation and was predominantly absent at sAML remission/relapsed PMF. Taken together, these findings illustrate the complex clonal dynamics associated with disease evolution in MPNs and sAML. PMID:25252869

  8. Long-term results of a phase II trial of lenalidomide plus prednisone therapy for patients with myelofibrosis.

    PubMed

    Chihara, Dai; Masarova, Lucia; Newberry, Kate J; Maeng, Hoyoung; Ravandi, Farhad; Garcia-Manero, Guillermo; Ferrajoli, Alessandra; Cortes, Jorge; Kantarjian, Hagop; Verstovsek, Srdan

    2016-09-01

    Lenalidomide, with or without prednisone, is an active therapy for patients with myelofibrosis (MF). We provide an update of a phase II study of lenalidomide plus prednisone in patients with MF, after median follow up of 9 years. Forty patients were enrolled in the study and all patients were evaluable for response. Response to the treatment was reevaluated using IWG response criteria published in 2013: quality of response improved over time and overall response rate was 35%. Response in splenomegaly was seen in 39% of patients and anemia response in 32%. The median time to treatment failure (TTF) in all patients was 8.2 months and the median duration of response was 34.6 months. Response was highly durable in some patients: six patients (15%) had TTF for more than 60 months (5 years) and three patients are still on the treatment beyond 109 months (9 years). Complete and partial responses were seen in one and five patients, respectively, but achieving deeper response was not necessary for the response to be durable. New clinical studies are needed to explore safe and well tolerated lenalidomide-based combination strategies for patients with MF.

  9. The changing profile of idiopathic myelofibrosis: a comparison of the presenting features of patients diagnosed in two different decades.

    PubMed

    Cervantes, F; Pereira, A; Esteve, J; Cobo, F; Rozman, C; Montserrat, E

    1998-02-01

    In an attempt to ascertain whether the presenting features of idiopathic myelofibrosis (IM) have changed in recent years, 2 groups of patients diagnosed with IM in a single institution in different time periods were compared. The first group included 53 patients diagnosed from 1975 to 1986, and the second included 56 patients diagnosed from 1987 to 1997. No significant differences were observed between the two groups with regard to age, gender, delay from first symptoms to disease diagnosis, peripheral blood hematological values and serum biochemical parameters. Patients diagnosed prior to 1987 presented more often with constitutional symptoms (fever, night sweats, weight loss), but the difference did not reach statistical significance. These latter patients had, however, a higher frequency of splenomegaly (91% vs. 73%, p=0.01) and hepatomegaly (79% vs. 48%, p=0.002), and were more often in the osteosclerotic phase at diagnosis (p=0.05) than patients more recently diagnosed. Finally, no significant differences were found between both groups in either the distribution by prognostic scores or survival. The above results seem to indicate a trend towards a less florid clinical picture of IM at presentation in recent years. This, however, does not result in a longer patient survival.

  10. X-linked thrombocytopenia with thalassemia displays bone marrow reticulin fibrosis and enhanced angiogenesis: comparisons with primary myelofibrosis.

    PubMed

    Åström, Maria; Hahn-Strömberg, Victoria; Zetterberg, Eva; Vedin, Inger; Merup, Mats; Palmblad, Jan

    2015-03-01

    X-linked thrombocytopenia with thalassemia (XLTT) is caused by the mutation 216R > Q in exon 4 of the GATA1 gene. Male hemizygous patients display macrothrombocytopenia, splenomegaly, and a β-thalassemia trait. We describe two XLTT families where three males were initially misdiagnosed as having primary myelofibrosis (PMF) and all five investigated males showed mild-moderate bone marrow (BM) reticulin fibrosis. Comparative investigations were performed on blood samples and BM biopsies from males with XLTT, PMF patients and healthy controls. Like PMF, XLTT presented with high BM microvessel density, low GATA1 protein levels in megakaryocytes, and elevated blood CD34+ cell counts. But unlike PMF, the BM microvessel pericyte coverage was low in XLTT, and no collagen fibrosis was found. Further, as evaluated by immunohistochemistry, expressions of the growth factors VEGF, AGGF1, and CTGF were low in XLTT megakaryocytes and microvessels but high in PMF. Thus, although the reticulin fibrosis in XLTT might simulate PMF, opposing stromal and megakaryocyte features may facilitate differential diagnosis. Additional comparisons between these disorders may increase the understanding of mechanisms behind BM fibrosis in relation to pathological megakaryopoiesis.

  11. Dualism of mixed chimerism between hematopoiesis and stroma in chronic idiopathic myelofibrosis after allogeneic stem cell transplantation.

    PubMed

    Thiele, J; Varus, E; Siebolts, U; Kvasnicka, H M; Wickenhauser, C; Metz, K A; Beelen, D W; Ditschkowski, M; Zander, A; Kröger, N

    2007-04-01

    Scant knowledge exists concerning lineage-restricted mixed chimerism (mCh) after allogeneic peripheral blood stem cell transplantation (PSCT) in patients with chronic idiopathic myelofibrosis (CIMF). Following a sex-mismatched PSCT, a combined immunopheno- and genotyping by fluorescence in-situ hybridization (FISH) was performed on sequential bone marrow (BM) biopsies at standardized intervals. Results were compared with PCR analysis of corresponding peripheral blood samples in five patients. According to FISH, pretransplant specimens revealed a gender congruence of more than 99%, while in the first three months the total BM exhibited a persistent fraction of host cells (30% to 40%) with a tendency to decline after about one year. It is noteworthy that the majority of endothelial cells maintained a recipient origin, whereas CD34+ progenitors and especially CD61+ megakaryocytes exhibited only very few host-derived cells. In keeping with the prevalence of donor cells in the hematopoietic compartment, PCR analysis of peripheral blood cells displayed a non-significant degree of mCh. In conclusion, according to FISH and PCR analysis, successful PSCT in CIMF results in an almost complete chimeric (donor-derived) state of the hematopoietic cell population. The non-transplantable stromal compartment includes the vascular endothelium with a predominance of recipient cells. The minimal mCh of this population implies probably a donor-derived origin (endothelial progenitor cells).

  12. Role of Myelofibrosis in Hematotoxicity of Munition RDX Environmental Degradation Product MNX

    DTIC Science & Technology

    2008-09-01

    consequence of anemia in the absence of sufficient regeneration from bone marrow erythroid precursors is recruitment of extramedullatory sites of...Another event associated with a successful regeneration of an anemic episode is increased reticulocytes in the peripheral blood. We quantitated...planned. Statistics: Effects of MNX and RDX on endpoints with normally distributed data ( EPO , BUN, liver weights) were determined by ANOVA with post

  13. Risk factors for infections in myelofibrosis: role of disease status and treatment. A multicenter study of 507 patients.

    PubMed

    Polverelli, Nicola; Breccia, Massimo; Benevolo, Giulia; Martino, Bruno; Tieghi, Alessia; Latagliata, Roberto; Sabattini, Elena; Riminucci, Mara; Godio, Laura; Catani, Lucia; Nicolosi, Maura; Perricone, Margherita; Sollazzo, Daria; Colafigli, Gioia; Campana, Anna; Merli, Francesco; Vitolo, Umberto; Alimena, Giuliana; Martinelli, Giovanni; Lewis, Russell E; Vianelli, Nicola; Cavo, Michele; Palandri, Francesca

    2017-01-01

    Although infectious complications represent a relevant cause of morbidity and mortality in patients with myelofibrosis (MF), little is known about their incidence, outcome and risk factors. We retrospectively evaluated a cohort of 507 MF patients, diagnosed between 1980 and 2014 in five Italian hematology centers, to define the epidemiology of infections and describe the impact of ruxolitinib (RUX) treatment. Overall, 112 patients (22%) experienced 160 infectious events (grade 3-4, 45%) for an incidence rate of 3.9% per patient-year. Infections were mainly bacterial (78%) and involving the respiratory tract (52% of cases). Also, viral (11%) and fungal infections (2%) were recorded. Overall, infections were fatal in 9% of the cases. Among baseline features, high/intermediate-2 IPSS category (HR 1.8, 95%CI:1.2-2.7; P = 0.02) and spleen length ≥10 cm below left costal margin (HR 1.6, 95%CI:1.1-2.5; P = 0.04) were associated with higher infectious risk in multivariate analysis. Overall, the rate of infections was higher in the cohort of 128 RUX-treated patients (44% vs. 20%, P < 0.001). In conclusion, IPSS-category and splenomegaly, emerged as the main risk factors for infections in MF. RUX-treated patients experienced significantly more infection episodes; however, future prospective studies are needed to isolate the confounding contribution of other risk factors such as disease stage. Am. J. Hematol. 92:37-41, 2017. © 2016 Wiley Periodicals, Inc.

  14. A Pilot Study of Quantitative MRI Parametric Response Mapping of Bone Marrow Fat for Treatment Assessment in Myelofibrosis

    PubMed Central

    Luker, Gary D.; Nguyen, Huong (Marie); Hoff, Benjamin A.; Galbán, Craig J.; Hernando, Diego; Chenevert, Thomas L.; Talpaz, Moshe; Ross, Brian D.

    2016-01-01

    Myelofibrosis (MF) is a hematologic neoplasm arising as a primary disease or secondary to other myeloproliferative neoplasms (MPNs). Both primary and secondary MF are uniquely associated with progressive bone marrow fibrosis, displacing normal hematopoietic cells from the marrow space and disrupting normal production of mature blood cells. Activation of the JAK2 signaling pathway in hematopoietic stem cells commonly causes MF, and ruxolitinib, a drug targeting this pathway, is the treatment of choice for many patients. However, current measures of disease status in MF do not necessarily predict response to treatment with ruxolitinib or other drugs in MF. Bone marrow biopsies are invasive and prone to sampling error, while measurements of spleen volume only indirectly reflect bone marrow status. Toward the goal of developing an imaging biomarker for treatment response in MF, we present preliminary results from a prospective clinical study evaluating parametric response mapping (PRM) of quantitative Dixon MRI bone marrow fat fraction maps in four MF patients treated with ruxolitinib. PRM allows for the voxel-wise identification of significant change in quantitative imaging readouts over time, in this case the bone marrow fat content. We identified heterogeneous response patterns of bone marrow fat among patients and within different bone marrow sites in the same patient. We also observed discordance between changes in bone marrow fat fraction and reductions in spleen volume, the standard imaging metric for treatment efficacy. This study provides initial support for PRM analysis of quantitative MRI of bone marrow fat to monitor response to therapy in MF, setting the stage for larger studies to further develop and validate this method as a complementary imaging biomarker for this disease. PMID:27213182

  15. Loss of Ezh2 synergizes with JAK2-V617F in initiating myeloproliferative neoplasms and promoting myelofibrosis

    PubMed Central

    Nienhold, Ronny; Zmajkovic, Jakub; Hao-Shen, Hui; Geier, Florian; Dirnhofer, Stephan; Feenstra, Jelena D. Milosevic

    2016-01-01

    Myeloproliferative neoplasm (MPN) patients frequently show co-occurrence of JAK2-V617F and mutations in epigenetic regulator genes, including EZH2. In this study, we show that JAK2-V617F and loss of Ezh2 in hematopoietic cells contribute synergistically to the development of MPN. The MPN phenotype induced by JAK2-V617F was accentuated in JAK2-V617F;Ezh2−/− mice, resulting in very high platelet and neutrophil counts, more advanced myelofibrosis, and reduced survival. These mice also displayed expansion of the stem cell and progenitor cell compartments and a shift of differentiation toward megakaryopoiesis at the expense of erythropoiesis. Single cell limiting dilution transplantation with bone marrow from JAK2-V617F;Ezh2+/− mice showed increased reconstitution and MPN disease initiation potential compared with JAK2-V617F alone. RNA sequencing in Ezh2-deficient hematopoietic stem cells (HSCs) and megakaryocytic erythroid progenitors identified highly up-regulated genes, including Lin28b and Hmga2, and chromatin immunoprecipitation (ChIP)–quantitative PCR (qPCR) analysis of their promoters revealed decreased H3K27me3 deposition. Forced expression of Hmga2 resulted in increased chimerism and platelet counts in recipients of retrovirally transduced HSCs. JAK2-V617F–expressing mice treated with an Ezh2 inhibitor showed higher platelet counts than vehicle controls. Our data support the proposed tumor suppressor function of EZH2 in patients with MPN and call for caution when considering using Ezh2 inhibitors in MPN. PMID:27401344

  16. Impact of JAK2V617F Mutational Status on Phenotypic Features in Essential Thrombocythemia and Primary Myelofibrosis

    PubMed Central

    Yönal, İpek; Dağlar-Aday, Aynur; Akadam-Teker, Başak; Yılmaz, Ceylan; Nalçacı, Meliha; Yavuz, Akif Selim; Sargın, Fatma Deniz

    2016-01-01

    Objective: The JAK2V617F mutation is present in the majority of patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF). The impact of this mutation on disease phenotype in ET and PMF is still a matter of discussion. This study aims to determine whether there are differences in clinical presentation and disease outcome between ET and PMF patients with and without the JAK2V617F mutation. Materials and Methods: In this single-center study, a total of 184 consecutive Philadelphia-negative chronic myeloproliferative neoplasms, 107 cases of ET and 77 cases of PMF, were genotyped for JAK2V617F mutation using the JAK2 Ipsogen MutaScreen assay, which involves allele-specific polymerase chain reaction. Results: ET patients positive for JAK2V617F mutation had higher hemoglobin (Hb) and hematocrit (Hct) levels, lower platelet counts, and more prevalent splenomegaly at diagnosis compared to patients negative for the JAK2V617F mutation, but rates of major thrombotic events, arterial thrombosis, and venous thrombosis were comparable between the groups. At presentation, PMF patients with JAK2V617F mutation had significantly higher Hb and Hct levels and leukocyte counts than patients without the mutation. Similar to the findings of ET patients, thromboembolic rates were similar in PMF patients with and without theJAK2V617F mutation. For ET and PMF patients, no difference was observed in rates of death with respect to JAK2V617F mutational status. Moreover, leukemic transformation rate was not different in our PMF patients with and without JAK2V617F mutation. Conclusion: We conclude that JAK2V617F-mutated ET patients express a polycythemia vera-like phenotype and JAK2V617F mutation in PMF patients is associated with a more pronounced myeloproliferative phenotype. PMID:25913509

  17. The loss of Ezh2 drives the pathogenesis of myelofibrosis and sensitizes tumor-initiating cells to bromodomain inhibition

    PubMed Central

    Kanai, Akinori; Mochizuki-Kashio, Makiko; Harada, Hironori; Shimoda, Kazuya

    2016-01-01

    EZH2 is a component of polycomb repressive complex 2 (PRC2) and functions as an H3K27 methyltransferase. Loss-of-function mutations in EZH2 are associated with poorer outcomes in patients with myeloproliferative neoplasms (MPNs), particularly those with primary myelofibrosis (MF [PMF]). To determine how EZH2 insufficiency is involved in the pathogenesis of PMF, we generated mice compound for an Ezh2 conditional deletion and activating mutation in JAK2 (JAK2V617F) present in patients with PMF. The deletion of Ezh2 in JAK2V617F mice markedly promoted the development of MF, indicating a tumor suppressor function for EZH2 in PMF. The loss of Ezh2 in JAK2V617F hematopoietic cells caused significant reductions in H3K27 trimethylation (H3K27me3) levels, resulting in an epigenetic switch to H3K27 acetylation (H3K27ac). These epigenetic switches were closely associated with the activation of PRC2 target genes including Hmga2, an oncogene implicated in the pathogenesis of PMF. The treatment of JAK2V617F/Ezh2-null mice with a bromodomain inhibitor significantly attenuated H3K27ac levels at the promoter regions of PRC2 targets and down-regulated their expression, leading to the abrogation of MF-initiating cells. Therefore, an EZH2 insufficiency not only cooperated with active JAK2 to induce MF, but also conferred an oncogenic addiction to the H3K27ac modification in MF-initiating cells that was capable of being restored by bromodomain inhibition. PMID:27401345

  18. Enhanced Expression of Stim, Orai, and TRPC Transcripts and Proteins in Endothelial Progenitor Cells Isolated from Patients with Primary Myelofibrosis

    PubMed Central

    Dragoni, Silvia; Laforenza, Umberto; Bonetti, Elisa; Reforgiato, Marta; Poletto, Valentina; Lodola, Francesco; Bottino, Cinzia; Guido, Daniele; Rappa, Alessandra; Pareek, Sumedha; Tomasello, Mario; Guarrera, Maria Rosa; Cinelli, Maria Pia; Aronica, Adele; Guerra, Germano; Barosi, Giovanni; Tanzi, Franco

    2014-01-01

    Background An increase in the frequency of circulating endothelial colony forming cells (ECFCs), the only subset of endothelial progenitor cells (EPCs) truly belonging to the endothelial phenotype, occurs in patients affected by primary myelofibrosis (PMF). Herein, they might contribute to the enhanced neovascularisation of fibrotic bone marrow and spleen. Store-operated Ca2+ entry (SOCE) activated by the depletion of the inositol-1,4,5-trisphosphate (InsP3)-sensitive Ca2+ store drives proliferation in ECFCs isolated from both healthy donors (N-ECFCs) and subjects suffering from renal cellular carcinoma (RCC-ECFCs). SOCE is up-regulated in RCC-ECFCs due to the over-expression of its underlying molecular components, namely Stim1, Orai1, and TRPC1. Methodology/Principal Findings We utilized Ca2+ imaging, real-time polymerase chain reaction, western blot analysis and functional assays to evaluate molecular structure and the functional role of SOCE in ECFCs derived from PMF patients (PMF-ECFCs). SOCE, induced by either pharmacological (i.e. cyclopiazonic acid or CPA) or physiological (i.e. ATP) stimulation, was significantly higher in PMF-ECFCs. ATP-induced SOCE was inhibited upon blockade of the phospholipase C/InsP3 signalling pathway with U73111 and 2-APB. The higher amplitude of SOCE was associated to the over-expression of the transcripts encoding for Stim2, Orai2–3, and TRPC1. Conversely, immunoblotting revealed that Stim2 levels remained constant as compared to N-ECFCs, while Stim1, Orai1, Orai3, TRPC1 and TRPC4 proteins were over-expressed in PMF-ECFCs. ATP-induced SOCE was inhibited by BTP-2 and low micromolar La3+ and Gd3+, while CPA-elicited SOCE was insensitive to Gd3+. Finally, BTP-2 and La3+ weakly blocked PMF-ECFC proliferation, while Gd3+ was ineffective. Conclusions Two distinct signalling pathways mediate SOCE in PMF-ECFCs; one is activated by passive store depletion and is Gd3+-resistant, while the other one is regulated by the InsP3-sensitive Ca2

  19. Primary analysis of a phase II open-label trial of INCB039110, a selective JAK1 inhibitor, in patients with myelofibrosis

    PubMed Central

    Mascarenhas, John O.; Talpaz, Moshe; Gupta, Vikas; Foltz, Lynda M.; Savona, Michael R.; Paquette, Ronald; Turner, A. Robert; Coughlin, Paul; Winton, Elliott; Burn, Timothy C.; O’Neill, Peter; Clark, Jason; Hunter, Deborah; Assad, Albert; Hoffman, Ronald; Verstovsek, Srdan

    2017-01-01

    Combined Janus kinase 1 (JAK1) and JAK2 inhibition therapy effectively reduces splenomegaly and symptom burden related to myelofibrosis but is associated with dose-dependent anemia and thrombocytopenia. In this open-label phase II study, we evaluated the efficacy and safety of three dose levels of INCB039110, a potent and selective oral JAK1 inhibitor, in patients with intermediate- or high-risk myelofibrosis and a platelet count ≥50×109/L. Of 10, 45, and 32 patients enrolled in the 100 mg twice-daily, 200 mg twice-daily, and 600 mg once-daily cohorts, respectively, 50.0%, 64.4%, and 68.8% completed week 24. A ≥50% reduction in total symptom score was achieved by 35.7% and 28.6% of patients in the 200 mg twice-daily cohort and 32.3% and 35.5% in the 600 mg once-daily cohort at week 12 (primary end point) and 24, respectively. By contrast, two patients (20%) in the 100 mg twice-daily cohort had ≥50% total symptom score reduction at weeks 12 and 24. For the 200 mg twice-daily and 600 mg once-daily cohorts, the median spleen volume reductions at week 12 were 14.2% and 17.4%, respectively. Furthermore, 21/39 (53.8%) patients who required red blood cell transfusions during the 12 weeks preceding treatment initiation achieved a ≥50% reduction in the number of red blood cell units transfused during study weeks 1–24. Only one patient discontinued for grade 3 thrombocytopenia. Non-hematologic adverse events were largely grade 1 or 2; the most common was fatigue. Treatment with INCB039110 resulted in clinically meaningful symptom relief, modest spleen volume reduction, and limited myelosuppression. PMID:27789678

  20. Primary analysis of a phase II open-label trial of INCB039110, a selective JAK1 inhibitor, in patients with myelofibrosis.

    PubMed

    Mascarenhas, John O; Talpaz, Moshe; Gupta, Vikas; Foltz, Lynda M; Savona, Michael R; Paquette, Ronald; Turner, A Robert; Coughlin, Paul; Winton, Elliott; Burn, Timothy C; O'Neill, Peter; Clark, Jason; Hunter, Deborah; Assad, Albert; Hoffman, Ronald; Verstovsek, Srdan

    2017-02-01

    Combined Janus kinase 1 (JAK1) and JAK2 inhibition therapy effectively reduces splenomegaly and symptom burden related to myelofibrosis but is associated with dose-dependent anemia and thrombocytopenia. In this open-label phase II study, we evaluated the efficacy and safety of three dose levels of INCB039110, a potent and selective oral JAK1 inhibitor, in patients with intermediate- or high-risk myelofibrosis and a platelet count ≥50×10(9)/L. Of 10, 45, and 32 patients enrolled in the 100 mg twice-daily, 200 mg twice-daily, and 600 mg once-daily cohorts, respectively, 50.0%, 64.4%, and 68.8% completed week 24. A ≥50% reduction in total symptom score was achieved by 35.7% and 28.6% of patients in the 200 mg twice-daily cohort and 32.3% and 35.5% in the 600 mg once-daily cohort at week 12 (primary end point) and 24, respectively. By contrast, two patients (20%) in the 100 mg twice-daily cohort had ≥50% total symptom score reduction at weeks 12 and 24. For the 200 mg twice-daily and 600 mg once-daily cohorts, the median spleen volume reductions at week 12 were 14.2% and 17.4%, respectively. Furthermore, 21/39 (53.8%) patients who required red blood cell transfusions during the 12 weeks preceding treatment initiation achieved a ≥50% reduction in the number of red blood cell units transfused during study weeks 1-24. Only one patient discontinued for grade 3 thrombocytopenia. Non-hematologic adverse events were largely grade 1 or 2; the most common was fatigue. Treatment with INCB039110 resulted in clinically meaningful symptom relief, modest spleen volume reduction, and limited myelosuppression.

  1. Safety and efficacy of ruxolitinib in an open-label, multicenter, single-arm phase 3b expanded-access study in patients with myelofibrosis: a snapshot of 1144 patients in the JUMP trial

    PubMed Central

    Al-Ali, Haifa Kathrin; Griesshammer, Martin; le Coutre, Philipp; Waller, Cornelius F.; Liberati, Anna Marina; Schafhausen, Philippe; Tavares, Renato; Giraldo, Pilar; Foltz, Lynda; Raanani, Pia; Gupta, Vikas; Tannir, Bayane; Ronco, Julian Perez; Ghosh, Jagannath; Martino, Bruno; Vannucchi, Alessandro M.

    2016-01-01

    JUMP is a phase 3b expanded-access trial for patients without access to ruxolitinib outside of a clinical study; it is the largest clinical trial to date in patients with myelofibrosis who have been treated with ruxolitinib. Here, we present safety and efficacy findings from an analysis of 1144 patients with intermediate- or high-risk myelofibrosis, as well as a separate analysis of 163 patients with intermediate-1-risk myelofibrosis – a population of patients not included in the phase 3 COMFORT studies. Consistent with ruxolitinib’s mechanism of action, the most common hematologic adverse events were anemia and thrombocytopenia, but these led to treatment discontinuation in only a few cases. The most common non-hematologic adverse events were primarily grade 1/2 and included diarrhea, pyrexia, fatigue, and asthenia. The rates of infections were low and primarily grade 1/2, and no new or unexpected infections were observed. The majority of patients achieved a ≥50% reduction from baseline in palpable spleen length. Improvements in symptoms were rapid, with approximately half of all patients experiencing clinically significant improvements, as assessed by various quality-of-life questionnaires. The safety and efficacy profile in intermediate-1-risk patients was consistent with that in the overall JUMP population and with that previously reported in intermediate-2- and high-risk patients. Overall, ruxolitinib provided clinically meaningful reductions in spleen length and symptoms in patients with myelofibrosis, including those with intermediate-1-risk disease, with a safety and efficacy profile consistent with that observed in the phase 3 COMFORT studies. This trial was registered as NCT01493414 at ClinicalTrials.gov. PMID:27247324

  2. Allogeneic haematopoietic stem cell transplantation for myelofibrosis: a report of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC).

    PubMed

    Robin, Marie; Tabrizi, Reza; Mohty, Mohamad; Furst, Sabine; Michallet, Mauricette; Bay, Jacques-Olivier; Cahn, Jean-Yves; De Coninck, Eric; Dhedin, Nathalie; Bernard, Marc; Rio, Bernard; Buzyn, Agnès; Huynh, Anne; Bilger, Karin; Bordigoni, Pierre; Contentin, Nathalie; Porcher, Raphaël; Socié, Gérard; Milpied, Noel

    2011-02-01

    Allogeneic haematopoietic stem-cell transplantation (HSCT) is the only curative treatment for myelofibrosis. We report an analysis of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) registry including patients with myelofibrosis transplanted between 1997 and 2008. Potential risk factors affecting engraftment, non-relapse mortality (NRM), overall survival (OS) and progression-free survival (PFS) were analysed. One hundred and forty-seven patients, aged 20-68 (median 53) years, diagnosed with primary (53%) or secondary myelofibrosis underwent HSCT; 59% of patients were transplanted from a matched sibling donor. The conditioning regimen was myeloablative in 31% of patients. Ninety percent of the patients engrafted. Factors affecting favourably engraftment were splenectomy before HSCT, human leucocyte antigen (HLA) matched sibling donor, peripheral stem cell use as source of stem cells and absence of pre-transplant thrombocytopenia. Four-year OS, PFS and NRM survival were 39% (95%confidence interval [CI]: 31-50), 32% (95%CI: 24-43) and 39% (95%CI 30-48), respectively. Multivariate analysis indicated that HLA-identical sibling donor, chronic phase disease and splenectomy in men had favourable impact on OS.

  3. Bone geometry, bone mineral density, and micro-architecture in patients with myelofibrosis: a cross-sectional study using DXA, HR-pQCT, and bone turnover markers.

    PubMed

    Farmer, Sarah; Vestergaard, Hanne; Hansen, Stinus; Shanbhogue, Vikram Vinod; Shanbhoque, Vikram Vinod; Stahlberg, Claudia Irene; Hermann, Anne Pernille; Frederiksen, Henrik

    2015-07-01

    Primary myelofibrosis (MF) is a severe chronic myeloproliferative neoplasm, progressing towards a terminal stage with insufficient haematopoiesis and osteosclerotic manifestations. Whilst densitometry studies have showed MF patients to have elevated bone mineral density, data on bone geometry and micro-structure assessed with non-invasive methods are lacking. We measured areal bone mineral density (aBMD) using dual-energy X-ray absorptiometry (DXA). Bone geometry, volumetric BMD, and micro-architecture were measured using high-resolution peripheral quantitative computed tomography (HR-pQCT). We compared the structural parameters of bones by comparing 18 patients with MF and healthy controls matched for age, sex, and height. Blood was analysed for biochemical markers of bone turnover in patients with MF. There were no significant differences in measurements of bone geometry, volumetric bone mineral density, and micro-structure between MF patients and matched controls. Estimated bone stiffness and bone strength were similar between MF patients and controls. The level of pro-collagen type 1 N-terminal pro-peptide (P1NP) was significantly increased in MF, which may indicate extensive collagen synthesis, one of the major diagnostic criteria in MF. We conclude that bone mineral density, geometry, and micro-architecture in this cohort of MF patients are comparable with those in healthy individuals.

  4. REDUCED INTENSITY HEMATOPOIETIC CELL TRANSPLANTATION FOR PATIENTS WITH PRIMARY MYELOFIBROSIS: A COHORT ANALYSIS FROM THE CENTER FOR INTERNATIONAL BLOOD AND MARROW TRANSPLANT RESEARCH

    PubMed Central

    Gupta, Vikas; Malone, Adriana K.; Hari, Parameswaran N.; Ahn, Kwang Woo; Hu, Zhen-Huan; Gale, Robert Peter; Ballen, Karen K.; Hamadani, Mehdi; Olavarria, Eduardo; Gerds, Aaron T.; Waller, Edmund K.; Costa, Luciano J.; Antin, Joseph H.; Kamble, Rammurti T.; van Besien, Koen M.; Savani, Bipin N.; Schouten, Harry C.; Szer, Jeffrey; Cahn, Jean-Yves; de Lima, Marcos J.; Wirk, Baldeep; Aljurf, Mahmoud D.; Popat, Uday; Bejanyan, Nelli; Litzow, Mark R.; Norkin, Maxim; Lewis, Ian D.; Hale, Gregory A.; Woolfrey, Ann E.; Miller, Alan M.; Ustun, Celalettin; Jagasia, Madan H.; Lill, Michael; Maziarz, Richard T.; Cortes, Jorge; Kalaycio, Matt E.; Saber, Wael

    2014-01-01

    We evaluated the outcomes and associated prognostic factors in 233 patients undergoing allogeneic hematopoietic cell transplantation (HCT) for primary myelofibrosis (MF) using reduced intensity conditioning (RIC). Median age at HCT was 55 years. Donors were: matched sibling donor (MSD), 34%; HLA-well-matched unrelated donors (URD), 45%; and partially/mismatched URD, 21%. Risk stratification according to Dynamic International Prognostic Scoring System (DIPSS): low, 12%; intermediate-1, 49%; intermediate-2, 37%; and high, 1%. The probability of survival at 5-years was 47% (95% CI 40–53). In a multivariate analysis, donor type was the only independent factor associated with survival. Adjusted probabilities of survival at 5-years for MSD, well matched URD and partially matched/mismatched URD were 56% (95% CI 44–67), 48% (95% CI 37–58), and 34% (95% CI 21–47), respectively (p=0.002). Relative risks (RR) for NRM for well-matched URD and partially matched/mismatched URD were 3.92 (p=0.006) and 9.37 (p<0.0001), respectively. A trend towards increased NRM (RR 1.7, p=0.07) and inferior survival (RR 1.37, p=0.10) was observed in DIPSS-intermediate-2/high-risk patients compared to DIPSS-low/intermediate-1 risk patients. RIC HCT is a potentially curative option for patients with MF, and donor type is the most important factor influencing survival in these patients. PMID:24161923

  5. Splenic irradiation in the treatment of patients with chronic myelogenous leukemia or myelofibrosis with myeloid metaplasia. Results of daily and intermittent fractionation with and without concomitant hydroxyurea

    SciTech Connect

    Wagner, H. Jr.; McKeough, P.G.; Desforges, J.; Madoc-Jones, H.

    1986-09-15

    Seventeen patients with either chronic myelogenous leukemia (CML) or myelofibrosis with myeloid metaplasia (MMM) received 24 courses of splenic irradiation at this institution from 1973 to 1982. Eleven of the 17 patients had received prior chemotherapy. Patients were treated with /sup 60/Co gamma rays or 6 MV photons. The fraction size ranged from 15 to 100 rad and the total dose per treatment course from 15 to 650 rad, with the exception of one patient who received 1650 rad. Fourteen of 19 courses (71%) given for splenic pain yielded significant subjective relief while 17 of 26 courses given for splenomegaly obtained at least 50% regression of splenic size. Blood counts were carefully monitored before each treatment to limit hematologic toxicity. From this experience, the authors conclude that splenic irradiation effectively palliates splenic pain and reverses splenomegaly in the majority of patients with CML and MMM. Intermittent fractionation (twice or thrice weekly) is more convenient for the patient, appears to be as effective as daily treatment, and may be associated with less hematologic toxicity. Preliminary results of concurrent treatment with splenic irradiation and oral hydroxyurea show promise and warrant further study.

  6. Application of an NGS-based 28-gene panel in myeloproliferative neoplasms reveals distinct mutation patterns in essential thrombocythaemia, primary myelofibrosis and polycythaemia vera.

    PubMed

    Delic, Sabit; Rose, Dominic; Kern, Wolfgang; Nadarajah, Niroshan; Haferlach, Claudia; Haferlach, Torsten; Meggendorfer, Manja

    2016-11-01

    Molecular routine diagnostics for BCR-ABL1-negative myeloproliferative neoplasms (MPN) currently focusses on mutations in JAK2, CALR and MPL. In recent years, recurrent mutations in MPNs have been identified in several other genes. We here present the validation of a next generation sequencing (NGS)-based 28-gene panel and its use in MPN. We analysed the mutation status of 28 genes in 100 MPN patients [40 essential thrombocythaemia (ET), 30 primary myelofibrosis (PMF), 30 polycythaemia vera (PV)] and found two or more mutated genes in 53 patients. Moreover, significantly more mutated splicing genes (SF3B1, SRSF2 and U2AF1) were present in PMF (0·60 mutated genes/patient) compared to ET (0·15) while no mutations in splicing genes were found in PV. Additionally, chromatin modification genes (ASXL1 and EZH2) were frequently mutated in PMF patients (0·50) and, to a significantly lesser extent, in ET (0·13) and PV (0·07). Contrarily, DNA methylation genes (DNMT3A, IDH1, IDH2 and TET2) were mutated most often in PV (0·5) and less frequently in ET (0·23) and PMF (0·20), but without reaching statistical significance. Our results demonstrate the feasibility and utility of NGS-based panel diagnostics for MPN. With 53% of the patients bearing two or more mutated genes, their prognostic relevance needs further studies.

  7. Translocation t(3;12)(q26;q21) in JAK2V617F Point Mutation Negative Chronic Idiopathic Myelofibrosis: A Case Report

    PubMed Central

    Mešanović, S.; Šahović, H.; Perić, M.

    2014-01-01

    The myeloproliferative diseases (MPDs) or myelo-proliferative neoplasms (MPNs) are a group of diseases of the bone marrow in which excess cells are produced. Chronic idiopathic myelofibrosis (CIMF) is a stem cell defect characterized by splenomegaly with multiorgan extramedullary hematopoiesis, immature peripheral blood granulocytes and erythrocytes and progressive bone marrow fibrosis. The most common chromosomal abnormalities seen in CIMF patients include numerical changes of chromosomes 7, 8 and 9, and structural changes of 1q, 5q, 13q and 20q. At least 75.0% of patients with bone marrow abnormalities have one or more of these chromosomal anomalies. Detection of the Janus kinase 2 (JAK2) mutation may be a potential major breakthrough for understanding the pathobiology of MPNs, and is an essential part of the diagnostic algorithm. In this study, we describe a JAK2V617F mutation negative CIMF patient who has the chromosomal translocation t(3;12)(q26;q21) in her karyotype. PMID:25741217

  8. Telomere shortening in Ph-negative chronic myeloproliferative neoplasms: a biological marker of polycythemia vera and myelofibrosis, regardless of hydroxycarbamide therapy.

    PubMed

    Ruella, Marco; Salmoiraghi, Silvia; Risso, Alessandra; Carobbio, Alessandra; Buttiglieri, Stefano; Spatola, Tiziana; Sivera, Piera; Ricca, Irene; Barbui, Tiziano; Tarella, Corrado; Rambaldi, Alessandro

    2013-07-01

    The purpose of this study was to investigate telomere length (TL) in Ph-negative chronic myeloproliferative neoplasms (Ph-neg-CMNs), and the possible association of TL with disease progression and hydroxycarbamide (HU) treatment. TL was analyzed in peripheral blood samples from 239 patients with Ph-neg-CMNs, including polycythemia vera (PV), essential thrombocythemia and myelofibrosis (MF), and compared with age-matched healthy control subjects (CTR), along with some cases of secondary erythrocytosis (SE). More than half of the patients with CMN received at least 1 year of cytoreduction, mainly HU, before TL analysis. JAK2 mutation analysis was performed as well. TL was significantly shortened in patients with CMN compared with CTR (p < 0.0001). PV and MF showed the most pronounced decrease (p < 0.0001), whereas both essential thrombocythemia and SE showed no significant difference in TL compared with CTR. A short TL correlated with JAK2-V617F allele burden greater than 50% (p = 0.0025), age (p = 0.0132) and diagnosis of PV (p = 0.0122). No correlation was found with disease duration, history of thrombosis, cytoreductive treatment, antiaggregation agents, adverse cytogenetics, phlebotomies, or time to evolution to MF. In summary, TL is distinctly shortened in PV and MF, and it inversely correlates with JAK2V617F allele burden. In addition, HU is unlikely to contribute to telomere erosion. Lastly, PV and SE significantly differ in TL. Therefore, TL could be an additional diagnostic marker to identify and monitor Ph-neg-CMN patients.

  9. JAK2 Exon 14 Skipping in Patients with Primary Myelofibrosis: A Minor Splice Variant Modulated by the JAK2-V617F Allele Burden

    PubMed Central

    Catarsi, Paolo; Rosti, Vittorio; Morreale, Giacomo; Poletto, Valentina; Villani, Laura; Bertorelli, Roberto; Pedrazzini, Matteo; Zorzetto, Michele; Barosi, Giovanni

    2015-01-01

    Background Primary myelofibrosis (PMF) is an acquired clonal disease of the hematopoietic stem cell compartment, characterized by bone marrow fibrosis, anemia, splenomegaly and extramedullary hematopoiesis. About 60% of patients with PMF harbor a somatic mutation of the JAK2 gene (JAK2-V617F) in their hematopoietic lineage. Recently, a splicing isoform of JAK2, lacking exon 14 (JAK2Δ14) was described in patients affected by myeloproliferative diseases. Materials and Methods By using a specific RT-qPCR method, we measured the ratio between the splicing isoform and the JAK2 full-length transcript (JAK2+14) in granulocytes, isolated from peripheral blood, of forty-four patients with PMF and nine healthy donors. Results We found that JAK2Δ14 was only slightly increased in patients and, at variance with published data, the splicing isoform was also detectable in healthy controls. We also found that, in patients bearing the JAK2-V617F mutation, the percentage of mutated alleles correlated with the observed increase in JAK2Δ14. Homozygosity for the mutation was also associated with a higher level of JAK2+14. Bioinformatic analysis indicates the possibility that the G>T transversion may interfere with the correct splicing of exon 14 by modifying a splicing regulatory sequence. Conclusions Increased levels of JAK2 full-length transcript and a small but significant increase in JAK2 exon 14 skipping, are associated with the JAK2-V617F allele burden in PMF granulocytes. Our data do not confirm a previous claim that the production of the JAK2Δ14 isoform is related to the pathogenesis of PMF. PMID:25617626

  10. Role of miR-34a-5p in Hematopoietic Progenitor Cells Proliferation and Fate Decision: Novel Insights into the Pathogenesis of Primary Myelofibrosis

    PubMed Central

    Bianchi, Elisa; Ruberti, Samantha; Rontauroli, Sebastiano; Guglielmelli, Paola; Salati, Simona; Rossi, Chiara; Zini, Roberta; Tagliafico, Enrico; Vannucchi, Alessandro Maria; Manfredini, Rossella

    2017-01-01

    Primary Myelofibrosis (PMF) is a chronic Philadelphia-negative myeloproliferative neoplasm characterized by a skewed megakaryopoiesis and an overproduction of proinflammatory and profibrotic mediators that lead to the development of bone marrow (BM) fibrosis. Since we recently uncovered the upregulation of miR-34a-5p in PMF CD34+ hematopoietic progenitor cells (HPCs), in order to elucidate its role in PMF pathogenesis here we unravelled the effects of miR-34a-5p overexpression in HPCs. We showed that enforced expression of miR-34a-5p partially constrains proliferation and favours the megakaryocyte and monocyte/macrophage commitment of HPCs. Interestingly, we identified lymphoid enhancer-binding factor 1 (LEF1) and nuclear receptor subfamily 4, group A, member 2 (NR4A2) transcripts as miR-34a-5p-targets downregulated after miR-34a-5p overexpression in HPCs as well as in PMF CD34+ cells. Remarkably, the knockdown of NR4A2 in HPCs mimicked the antiproliferative effects of miR-34a-5p overexpression, while the silencing of LEF1 phenocopied the effects of miR-34a-5p overexpression on HPCs lineage choice, by favouring the megakaryocyte and monocyte/macrophage commitment. Collectively our data unravel the role of miR-34a-5p in HPCs fate decision and suggest that the increased expression of miR-34a-5p in PMF HPCs could be important for the skewing of megakaryopoiesis and the production of monocytes, that are key players in BM fibrosis in PMF patients. PMID:28098757

  11. Reduced-intensity hematopoietic cell transplantation for patients with primary myelofibrosis: a cohort analysis from the center for international blood and marrow transplant research.

    PubMed

    Gupta, Vikas; Malone, Adriana K; Hari, Parameswaran N; Ahn, Kwang Woo; Hu, Zhen-Huan; Gale, Robert Peter; Ballen, Karen K; Hamadani, Mehdi; Olavarria, Eduardo; Gerds, Aaron T; Waller, Edmund K; Costa, Luciano J; Antin, Joseph H; Kamble, Rammurti T; van Besien, Koen M; Savani, Bipin N; Schouten, Harry C; Szer, Jeffrey; Cahn, Jean-Yves; de Lima, Marcos J; Wirk, Baldeep; Aljurf, Mahmoud D; Popat, Uday; Bejanyan, Nelli; Litzow, Mark R; Norkin, Maxim; Lewis, Ian D; Hale, Gregory A; Woolfrey, Ann E; Miller, Alan M; Ustun, Celalettin; Jagasia, Madan H; Lill, Michael; Maziarz, Richard T; Cortes, Jorge; Kalaycio, Matt E; Saber, Wael

    2014-01-01

    We evaluated outcomes and associated prognostic factors in 233 patients undergoing allogeneic hematopoietic cell transplantation (HCT) for primary myelofibrosis (MF) using reduced-intensity conditioning (RIC). The median age at RIC HCT was 55 yr. Donors were a matched sibling donor (MSD) in 34% of RIC HCTs, an HLA well-matched unrelated donor (URD) in 45%, and a partially matched/mismatched URD in 21%. Risk stratification according to the Dynamic International Prognostic Scoring System (DIPSS) was 12% low, 49% intermediate-1, 37% intermediate-2, and 1% high. The probability of survival at 5 yr was 47% (95% confidence interval [CI], 40% to 53%). In a multivariate analysis, donor type was the sole independent factor associated with survival. Adjusted probabilities of survival at 5-yr were 56% (95% CI, 44% to 67%) for MSD, 48% (95% CI, 37% to 58%) for well-matched URD, and 34% (95% CI, 21% to 47%) for partially matched/mismatched URD (P = .002). The relative risk (RR) for NRM was 3.92 (P = .006) for well-matched URD and 9.37 (P < .0001) for partially matched/mismatched URD. Trends toward increased NRM (RR, 1.7; P = .07) and inferior survival (RR, 1.37; P = .10) were observed in DIPSS intermediate-2/high-risk patients compared with DIPSS low/intermediate-1 risk patients. Our data indicate that RIC HCT is a potentially curative option for patients with MF, and that donor type is the most important factor influencing survival in these patients.

  12. IDH mutations in primary myelofibrosis predict leukemic transformation and shortened survival: clinical evidence for leukemogenic collaboration with JAK2V617F.

    PubMed

    Tefferi, A; Jimma, T; Sulai, N H; Lasho, T L; Finke, C M; Knudson, R A; McClure, R F; Pardanani, A

    2012-03-01

    Isocitrate dehydrogenase (IDH) mutations are frequent in blast-phase myeloproliferative neoplasms and might therefore contribute to leukemic transformation. We examined this possibility in 301 consecutive patients with chronic-phase primary myelofibrosis (PMF). The mutant IDH was detected in 12 patients (4%): 7 IDH2 (5 R140Q, 1 R140W and 1 R172G) and 5 IDH1 (3 R132S and 2 R132C). In all, 6 (50%) of the 12 IDH-mutated patients also expressed JAK2V617F. Overall, 18 (6%) patients displayed only MPL and 164 (54.3%) only JAK2 mutations. Multivariable analysis that accounted for conventional risk factors disclosed inferior overall survival (OS; P=0.03) and leukemia-free survival (LFS; P=0.003) in IDH-mutated patients: OS hazard ratio (HR) was 0.39 (95% confidence interval (95% CI) 0.2-0.75), 0.50 (95% CI 0.27-0.95) and 0.53 (95% CI 0.23-1.2) for patients with no, JAK2 or MPL mutations, respectively. Further analysis disclosed a more pronounced effect for the mutant IDH on OS and LFS in the presence (P=0.0002 and P<0.0001, respectively) as opposed to the absence (P=0.34 and P=0.64) of concomitant JAK2V617F. Analysis of paired samples obtained during chronic- and blast-phase disease revealed the presence of both IDH and JAK2 mutations at both time points. Our observations suggest that IDH mutations in PMF are independent predictors of leukemic transformation and raise the possibility of leukemogenic collaboration with JAK2V617F.

  13. Outcome of Allogeneic Stem Cell Transplantation Following Reduced-Intensity Conditioninig Regimen in Patients With Idiopathic Myelofibrosis: the G.I.T.M.O. Experience

    PubMed Central

    Patriarca, Francesca; Bacigalupo, Andrea; Sperotto, Alessandra; Isola, Miriam; Bruno, Barbara; van Lint, Maria Teresa; Iori, Anna Paola; Di Bartolomeo, Paolo; Musso, Maurizio; Pioltelli, Pietro; Visani, Giuseppe; Iacopino, Pasquale; Fanin, Renato; Bosi., Alberto

    2010-01-01

    Background: Allogeneic stem cell transplantation (SCT) is a potentially curative treatment for myelofibrosis (MI), though limited by a high rate of transplant-related mortality (TRM). In the present study we evaluate the outcome of MI patients undergoing an allogenic SCT after reduced intensity conditioning (RIC) regimens, and the impact of prognostic factors. Design and methods: Fifty two patients were transplanted in 26 Italian centres between 1998 and 2006. We analyzed the influence of patient and disease clinical features before SCT and of transplant procedures on TRM and overall survival (OS) by means of univariate and multivariate analyses. Results: At SCT, median age was 52,5 years (32–68) and 89% of the patients had an intermediate or high Dupriez score. Conditioning regimens were based on fludarabine plus busulphan in 27% of patients, thiotepa plus cyclophosphamide in 46% and miscellaneous drug combinations in the other 27% of cases. Stem cells came from matched sibling donors for 75% of the patients and mismatched sibling or unrelated donors for the remaining 25%. The cumulative incidence of engraftment at day 90 after transplant was 83% (95% CI, 0.87–0.97). The estimated 1-year TRM was 30%. The estimated 3-year event-free-survival (EFS) and OS after hematopoietic SCT was 44% and 38% respectively. In multivariate analysis, an higher leukocyte count and circulating blasts in the peripheral blood before SCT significantly reduced EFS and OS respectively. Interpretation and conclusions: We conclude that the extension of the disease before transplantation based on the presence of circulating blasts and high leukocyte counts significantly affected the outcome after HSCT PMID:21415963

  14. Ruxolitinib in clinical practice for primary and secondary myelofibrosis: an analysis of safety and efficacy of Gruppo Laziale of Ph-negative MPN.

    PubMed

    Breccia, Massimo; Andriani, Alessandro; Montanaro, Marco; Abruzzese, Elisabetta; Buccisano, Francesco; Cedrone, Michele; Centra, Antonietta; Villivà, Nicoletta; Celesti, Francesca; Trawinska, Malgorzata Monica; Massaro, Fulvio; Di Veroli, Ambra; Anaclerico, Barbara; Colafigli, Gioia; Molica, Matteo; Spadea, Antonio; Petriccione, Luca; Cimino, Giuseppe; Latagliata, Roberto

    2017-03-01

    Ruxolitinib, a JAK1 and JAK2 inhibitor, has been tested and approved for the treatment of primary and secondary myelofibrosis (MF). Aim of our study is to report safety and efficacy of ruxolitinib in 98 patients affected by MF treated outside clinical trials and collected and treated consecutively by the Lazio Cooperative Group for Ph negative myeloproliferative diseases.There were 45 males and 53 females; median age was 61.8 years (range 35.3-88). Forty-five patients were diagnosed as primary MF and 53 as secondary MF. Seventy-seven patients (78.5%) experienced constitutional symptoms at baseline, and out of 94 patients tested, 66 (70%) were JAK2(V617F) mutated. Overall, 40 patients received hydroxyurea as firstline treatment, 30 patients received other chemotherapeutic approaches, whereas 28 were treated with ruxolitinib frontline. Median time from diagnosis to start of ruxolitinib in the whole cohort was 34.6 months. Fifty-eight patients (59%) required a dose reduction during the first 3 months due to hematological toxicity in the majority of cases. At 48 weeks, 52% of patients obtained a clinical benefit: of them 7 patients (7%) had a CR, 10 (10%) a PR, 6 patients (6%) a CI, and 28 patients (28.5%) a spleen response. Overall, 66% of patients had disappearance of baseline symptoms burden. After 1 year, of 72 evaluable patients, 52% achieved and maintained a clinical benefit. Adverse events of special interest at any grade included anemia (39.7%), thrombocytopenia (25.5%), infections (16.3%, of which 10 were bronchopneumonia), fluid retention (3%), diarrhea (2%) and abdominal pain (2%). After a median follow-up of 16 months from start of ruxolitinib, median daily dose decreased to 10 mg BID and 21 patients (21%) discontinued the drug. The results of this retrospective multicentric analysis confirmed the efficacy of ruxolitinib outside clinical trials with more than half of treated patients achieving and maintaining a clinical benefit and most of them

  15. Genetics Home Reference: primary myelofibrosis

    MedlinePlus

    ... MPL genes are both part of a signaling pathway called the JAK/STAT pathway, which transmits chemical signals from outside the cell ... gene, called thrombopoietin receptor, turns on (activates) the pathway, and the JAK2 protein transmits signals after activation. ...

  16. Time Course and Variability of Polycythemic Response in Men at High Altitude

    NASA Technical Reports Server (NTRS)

    Grover, R. F.; Seiland, M.; McCullough, R. G.; Greenleaf, J. E.; Dahms, T. E.; Wolfel, E.; Reeves, J. T.

    2000-01-01

    Ten young men were exposed to 4,300 m (PB 460 Torr) for three weeks. Plasma volume (PV, Evans Blue dye). and blood volume (BV, carbon monoxide) measured simultaneously, and red cell volume (RCV) calculated from hematocrit, were determined twice at sea level and after 9-11 and 19-20 days at high altitude. After 19-20 days. half the subjects increased RCV +19.4 +/- 1.8% (p<0.001); the other 5 subjects had no significant change in RCV. All 10 subjects had a sustained decrease in PV (-16.2 +/- 1.9%, p<0.05) at altitude. Consequently, compared with sea level values, BV was unchanged (-3.1 +/- 1.8%) in the group with increased RCV, but BV decreased significantly (-12.2 +/- 1.4%, p<0.05) in the other group. Variability in RCV response was not explained by differences, in hypoxemic stimulus or the erythropoictin and reticulocyte responses. Since RCV reflects the balance between red cell. production and destruction, accelerated red cell destruction may have occurred in those individuals with no net change in RCV.

  17. The spleen microenvironment influences disease transformation in a mouse model of KITD816V-dependent myeloproliferative neoplasm

    PubMed Central

    Pelusi, Natalie; Kosanke, Maike; Riedt, Tamara; Rösseler, Corinna; Seré, Kristin; Li, Jin; Gütgemann, Ines; Zenke, Martin; Janzen, Viktor; Schorle, Hubert

    2017-01-01

    Activating mutations leading to ligand-independent signaling of the stem cell factor receptor KIT are associated with several hematopoietic malignancies. One of the most common alterations is the D816V mutation. In this study, we characterized mice, which conditionally express the humanized KITD816V receptor in the adult hematopoietic system to determine the pathological consequences of unrestrained KIT signaling during blood cell development. We found that KITD816V mutant animals acquired a myeloproliferative neoplasm similar to polycythemia vera, marked by a massive increase in red blood cells and severe splenomegaly caused by excessive extramedullary erythropoiesis. Moreover, we found mobilization of stem cells from bone marrow to the spleen. Splenectomy prior to KITD816V induction prevented expansion of red blood cells, but rapidly lead to a state of aplastic anemia and bone marrow fibrosis, reminiscent of post polycythemic myeloid metaplasia, the spent phase of polycythemia vera. Our results show that the extramedullary hematopoietic niche microenvironment significantly influences disease outcome in KITD816V mutant mice, turning this model a valuable tool for studying the interplay between functionally abnormal hematopoietic cells and their microenvironment during development of polycythemia vera-like disease and myelofibrosis. PMID:28128288

  18. Post-Nasal Drip

    MedlinePlus

    ... Find an ENT Doctor Near You Post-Nasal Drip Post-Nasal Drip Patient Health Information News media ... guaifenesin (Humibid®, Robitussin®) may also thin secretions. Nasal irrigations may alleviate thickened secretions. These can be performed ...

  19. Fence Posts and Rails

    ERIC Educational Resources Information Center

    Turton, Roger

    2016-01-01

    "Mathematical Lens" uses photographs as a springboard for mathematical inquiry and appears in every issue of "Mathematics Teacher." Recently while dismantling an old wooden post-and-rail fence, Roger Turton noticed something very interesting when he piled up the posts and rails together in the shape of a prism. The total number…

  20. Strain balanced quantum posts

    SciTech Connect

    Alonso-Alvarez, D.; Alen, B.; Ripalda, J. M.; Llorens, J. M.; Taboada, A. G.; Briones, F.; Roldan, M. A.; Hernandez-Saz, J.; Hernandez-Maldonado, D.; Herrera, M.; Molina, S. I.

    2011-04-25

    Quantum posts are assembled by epitaxial growth of closely spaced quantum dot layers, modulating the composition of a semiconductor alloy, typically InGaAs. In contrast with most self-assembled nanostructures, the height of quantum posts can be controlled with nanometer precision, up to a maximum value limited by the accumulated stress due to the lattice mismatch. Here, we present a strain compensation technique based on the controlled incorporation of phosphorous, which substantially increases the maximum attainable quantum post height. The luminescence from the resulting nanostructures presents giant linear polarization anisotropy.

  1. Post-Concussion Syndrome

    MedlinePlus

    ... those often experienced by people diagnosed with depression, anxiety or post-traumatic stress disorder. In many cases, both physiological effects of brain trauma and emotional reactions to these ...

  2. Post-Polio Syndrome

    MedlinePlus

    ... first episode of polio. Currently, the most accepted theory regarding the cause of post-polio syndrome rests ... conserve your energy. Moving from one frame of mind to another can be difficult. Here are some ...

  3. Mutations with epigenetic effects in myeloproliferative neoplasms and recent progress in treatment: Proceedings from the 5th International Post-ASH Symposium

    PubMed Central

    Tefferi, A; Abdel-Wahab, O; Cervantes, F; Crispino, J D; Finazzi, G; Girodon, F; Gisslinger, H; Gotlib, J; Kiladjian, J-J; Levine, R L; Licht, J D; Mullally, A; Odenike, O; Pardanani, A; Silver, R T; Solary, E; Mughal, T

    2011-01-01

    Immediately following the 2010 annual American Society of Hematology (ASH) meeting, the 5th International Post-ASH Symposium on Chronic Myelogenous Leukemia and BCR-ABL1-Negative Myeloproliferative Neoplasms (MPNs) took place on 7–8 December 2010 in Orlando, Florida, USA. During this meeting, the most recent advances in laboratory research and clinical practice, including those that were presented at the 2010 ASH meeting, were discussed among recognized authorities in the field. The current paper summarizes the proceedings of this meeting in BCR-ABL1-negative MPN. We provide a detailed overview of new mutations with putative epigenetic effects (TET oncogene family member 2 (TET2), additional sex comb-like 1 (ASXL1), isocitrate dehydrogenase (IDH) and enhancer of zeste homolog 2 (EZH2)) and an update on treatment with Janus kinase (JAK) inhibitors, pomalidomide, everolimus, interferon-α, midostaurin and cladribine. In addition, the new ‘Dynamic International Prognostic Scoring System (DIPSS)-plus' prognostic model for primary myelofibrosis (PMF) and the clinical relevance of distinguishing essential thrombocythemia from prefibrotic PMF are discussed. PMID:23471017

  4. Post adoption depression.

    PubMed

    Fields, Eve S; Meuchel, Jennifer M; Jaffe, Chiara J; Jha, Manish; Payne, Jennifer L

    2010-04-01

    We sought to evaluate the prevalence rate and factors associated with post adoption depression. One hundred and twelve adoptive mothers of infants under 12 months of age were recruited from local and national adoption organizations. A modified Edinburgh Postnatal Depression Scale (EPDS) and a questionnaire collecting medical and psychiatric history, perceived stress, and demographics were administered retrospectively. The rates of significant depressive symptoms (defined as EPDS >or=12) were calculated at three time points post adoption, and associations with specific clinical variables (personal or family psychiatric history, stress, and adjustment difficulty) were assessed. Eighty-six mothers were included. Rates of significant depressive symptoms (EPDS >or=12) were found in 27.9% of subjects at 0-4 weeks, 25.6% at 5-12 weeks, and 12.8% at 13-52 weeks post adoption. Significant depressive symptoms were not associated with personal or family psychiatric history but were associated with stress (p = 0.0011) and adjustment difficulties (p = 0.042) post adoption. Significant depressive symptoms were relatively common in adoptive mothers within the first year after adoption and were associated with environmental stress. Prospective studies are needed to confirm the existence of post adoption depression and the factors associated with it.

  5. Esthetic Intracanal Posts

    PubMed Central

    Parčina, Ivana; Amižić

    2016-01-01

    The primary function of an endodontic post is to provide retention for the core and enable full sealing of the coronal portion of the root canal. Traditionally used metal posts do not meet the requirements of modern dental medicine due to some fairly significant drawbacks such as color, corrosion potential, non-adhesive bonding and high modulus of elasticity which can lead to root fracture. Recently, esthetic ceramic and fiber reinforced posts have been manufactured in order to avoid such imperfections. Since much attention has been devoted to the esthetic aspects of dental medicine, the use of these posts with composite/ceramic cores is very common in restorative dentistry and it is actually becoming a standard. This is due to the fact that, apart from being an esthetically pleasing material, they are also biocompatible, have good physical properties and the capacity of adhesive bonding to tooth tissue and core buildup. Nonetheless, a good clinician should know how to spot the difference between them in order to select and use the appropriate post system in each specific situation. PMID:27789912

  6. The "Post-Post Period" and Environmental Education Research

    ERIC Educational Resources Information Center

    McKenzie, Marcia

    2005-01-01

    Described as "post-experimental" and of the "post-post period," the current moment in social science research is typified by multi-voiced texts, researcher reflexivity, cultural criticism, and experimental works; characteristics in keeping with post-structurally informed understandings of social science research as contingent, evolving and messy.…

  7. Myelofibrosis 2012: it’s complicated

    PubMed Central

    Hubbeling, Harper G.; Frank, Dale M.

    2012-01-01

    Major advances in myeloproliferative neoplasms in the last decade have cast light on their complexity. The identification of JAK2V617F briefly promised a unifying mechanism of pathogenesis with a single pathway that could be efficiently targeted. Instead, there have been major advances in understanding acquired and background genetic and epigenetic contributors to this group of disorders, with refined risk prediction models and experimental therapeutics that have provided a more nuanced model of disease. In aggregate these observations likely explain the heterogeneity of these disorders and their generally unpredictable response to therapy. Molecular studies, beginning with the identification of JAK2V617F, have led to a concept of MPN subtypes existing on a continuum, and additional discoveries such as TET2 and EZH2 mutations have provided the molecular underpinnings to begin to explain overlapping phenotypes in myeloid malignancies more generally. In many ways the pace of molecular discovery is outstripping our ability to integrate these observations into clinical care, both in terms of molecular diagnostics and medical decision making. This review will attempt to summarize, within a clinical context, our evolving understanding of myeloproliferative neoplasms. It focuses on biology, histopathology, prognostic scoring systems, stem cell transplantation as well as selected clinical/preclinical therapeutic observations. PMID:23556120

  8. [Post-transfusional AIDS].

    PubMed

    Azzini, M; Maccabruni, A; Marcellini, M; Michelone, G; Dei Cas, A

    1987-01-01

    Two cases of post-transfusional AIDS in two premature babies who received blood of the same seropositive donor, are reported. The risk of the susceptibility to HIV infection of these patients, in relation to the immaturity of immune system and to the transfusional treatment often necessary in premature newborns, is stressed.

  9. Unmanipulated haploidentical bone marrow transplantation and post-transplant cyclophosphamide for hematologic malignanices following a myeloablative conditioning: an update.

    PubMed

    Bacigalupo, A; Dominietto, A; Ghiso, A; Di Grazia, C; Lamparelli, T; Gualandi, F; Bregante, S; Van Lint, M T; Geroldi, S; Luchetti, S; Grasso, R; Pozzi, S; Colombo, N; Tedone, E; Varaldo, R; Raiola, A M

    2015-06-01

    This is a report of 148 patients with hematologic malignancies who received an unmanipulated haploidentical bone marrow transplant (BMT), followed by post-transplant high-dose cyclophosphamide (PT-CY). All patients received a myeloablative conditioning consisting of thiotepa, busulfan, fludarabine (n=92) or TBI, fludarabine (n=56). The median age was 47 years (17-74); 47 patients were in first remission (CR1), 37 in second remission (CR2) and 64 had an active disease; all patients were first grafts. The diagnosis was acute leukemia (n=75), myelodisplastic syndrome (n=24), myelofibrosis (n=16), high-grade lymphoma (n=15) and others (n=18). GVHD prophylaxis consisted in PT-CY on days +3 and +5, cyclosporine (from day 0), and mycophenolate (from day +1). The median day for neutrophil engraftment was day +18 (13-32). The cumulative incidence of grades II-IV acute GVHD was 24%, and of grades III-IV GVHD 10%. The incidence of moderate-severe chronic GVHD was 12%. With a median follow-up for the surviving patients of 313 days (100-1162), the cumulative incidence of transplant-related mortality (TRM) is 13%, and the relapse-related death is 23%. The actuarial 22 months overall survival is 77% for CR1 patients, 49% for CR2 patients and 38% for patients grafted in relapse (P<0.001). Major causes of death were relapse (22%), GVHD (2%) and infections (6%). We confirm our initial results, suggesting that a myeloablative conditioning regimen followed by unmanipulated haploidentical BMT with PT-CY, results in a low risk of acute and chronic GVHD and encouraging rates of TRM and overall survival, also for patients with active disease at the time of transplant.

  10. Typical Newel Post, First Floor Newel Post, Typical Baluster, Typical ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Typical Newel Post, First Floor Newel Post, Typical Baluster, Typical Nosing, First Floor Stringer Profile, Second Floor Stringer Profile - National Home for Disabled Volunteer Soldiers - Battle Mountain Sanitarium, Treasurer's Quarters, 500 North Fifth Street, Hot Springs, Fall River County, SD

  11. 10. FLOOR 1; CENTER POST AND POSTS UNDER STONE BEAMS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. FLOOR 1; CENTER POST AND POSTS UNDER STONE BEAMS WHICH SUPPORT BRIDGE BEAMS FOR BRIDGE TREES; WEDGES FOR ADJUSTING HEIGHT OF BRIDGE TREE CAN BE SEEN - Shelter Island Windmill, Manwaring Road, Shelter Island, Suffolk County, NY

  12. 1. Post card view of the bridge, c. 1910. Post ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. Post card view of the bridge, c. 1910. Post card courtesy Carol Poh Miller. Photocopy by Berni Rich, Score Photographers Cleveland, OH - B & O Railroad Bridge Number 464, Spanning Old Ship Canal & Cuyahoga River, Cleveland, Cuyahoga County, OH

  13. Post-stroke dyskinesias

    PubMed Central

    Nakawah, Mohammad Obadah; Lai, Eugene C

    2016-01-01

    Strokes, whether ischemic or hemorrhagic, are among the most common causes of secondary movement disorders in elderly patients. Stroke-related (vascular) movement disorders, however, are uncommon complications of this relatively common disease. The spectrum of post-stroke movement disorders is broad and includes both hypo- and hyperkinetic syndromes. Post-stroke dyskinesias are involuntary hyperkinetic movements arising from cerebrovascular insults and often present with mixed phenotypes of hyperkinesia which can sometimes be difficult to classify. Nevertheless, identification of the most relevant motor phenotype, whenever possible, allows for a more specific phenomenological categorization of the dyskinesia and thus helps guide its treatment. Fortunately, post-stroke dyskinesias are usually self-limiting and resolve within 6 to 12 months of onset, but a short-term pharmacotherapy might sometimes be required for symptom control. Functional neurosurgical interventions targeting the motor thalamus or globus pallidus interna might be considered for patients with severe, disabling, and persistent dyskinesias (arbitrarily defined as duration longer than 12 months). PMID:27853372

  14. Post-traumatic stress disorder

    MedlinePlus

    ... medlineplus.gov/ency/article/000925.htm Post-traumatic stress disorder To use the sharing features on this page, please enable JavaScript. Post-traumatic stress disorder (PTSD) is a type of anxiety disorder . ...

  15. Post dengue neurological complication.

    PubMed

    Hasliza, A H; Tohid, H; Loh, K Y; Santhi, P

    2015-01-01

    Dengue infection is highly endemic in many tropical countries including Malaysia. However, neurological complications arising from dengue infection is not common; Gullain-Barre syndrome (GBS) is one of these infrequent complications. In this paper, we have reported a case in which a 39-year-old woman presented with a neurological complication of dengue infection without typical symptoms and signs of dengue fever. She had a history of acute gastroenteritis (AGE) followed by an upper respiratory tract infection (URTI) weeks prior to her presentation rendering GBS secondary to the post viral URTI and AGE as the most likely diagnosis. Presence of thrombocytopenia was the only clue for dengue in this case.

  16. [Post-stripping telangiectasis].

    PubMed

    Hutinel, B; Maraval, M

    1985-01-01

    These telangiectasia appear between one and six months after the operation, especially in cases of capillary fragility. The most common localizations are the antero-internal and external sides of the thighs and knees. Unnecessary strippings, of continent saphenous veins, are the most frequent cause of these. Their prevention consists of the least possible traumatising stripping, using a fine stripper, a very rigorous post-operative support, and the wearing of light varicose stockings or tights for between one and three months. The treatment using microsclerosis, often delicate, should not be undertaken before six months.

  17. Castleman-Kojima disease (TAFRO syndrome) : a novel systemic inflammatory disease characterized by a constellation of symptoms, namely, thrombocytopenia, ascites (anasarca), microcytic anemia, myelofibrosis, renal dysfunction, and organomegaly : a status report and summary of Fukushima (6 June, 2012) and Nagoya meetings (22 September, 2012).

    PubMed

    Kawabata, Hiroshi; Takai, Kazue; Kojima, Masaru; Nakamura, Naoya; Aoki, Sadao; Nakamura, Shigeo; Kinoshita, Tomohiro; Masaki, Yasufumi

    2013-01-01

    Recently, a unique clinicopathologic variant of multicentric Castleman's disease (MCD) has been identified in Japan. This disease is characterized by a constellation of symptoms, as listed in the title, and multiple lymphadenopathy of mild degree with a pathologic diagnosis of atypical CD, often posing diagnostic and therapeutic problems for pathologists and hematologists, respectively. These findings suggest that this disease represents a novel clinical entity belonging to systemic inflammatory disorders with a background of immunological abnormality beyond the ordinal spectrum of MCD. To define this disorder more clearly, Japanese participants presented clinicopathologic data at the Fukushima and Nagoya meetings. Many of the patients presented by the participants were significantly accompanied by a combination of thrombocytopenia, ascites (anasarca), pleural effusions, microcytic anemia, fever, myelofibrosis, renal dysfunction, and organomegaly (TAFRO). Multiple lymphadenopathies were generally of mild degree, less than 1.5 cm in diameter, and consistently featured the histopathology of mixed- or less hyaline vascular-type CD. Autoantibodies were often detected. However, this disease did not fulfill the diagnostic criteria for well-known autoimmune diseases including systemic lupus erythematosus. Castleman-Kojima disease and TAFRO syndrome (the favored clinical term) were proposed for this disease. The patients were sensitive to steroid and anti-interleukin-6 receptor antibody (tocilizumab), but some exhibited a deteriorated clinical course despite the treatment. The participants proposed a future nationwide survey and a Japanese consortium to facilitate further clinical and therapeutic studies of this novel disease. [J Clin Exp Hematop 53(1): 57-61, 2013].

  18. Post-16 update

    NASA Astrophysics Data System (ADS)

    1999-01-01

    Post-16 Initiative logo This is the first of a regular series of contributions from the Institute's Post-16 Initiative. The Initiative is taking a hard and searching look at the physics taught in schools and colleges from age 16 to age 19. To start with, it is responding to Government initiatives, but hopes to encourage and stimulate good practice in physics teaching on a longer time scale than can be afforded in making responses to current developments. Here Jon Ogborn writes about what AS courses need to be, while Peter Campbell gives his thoughts about teaching matter. Advanced Subsidiary physics: what should it be? From September 2000 all A-levels will be new. Students can take the first Advanced Subsidiary (AS) year and stop there - or decide to go on. In the Institute of Physics post-16 Initiative, we have been thinking how to provide a satisfying one-year experience of physics at the new AS level, and what it should achieve. The students will decide. So the AS course must give a decent picture of what physics is, what it offers for their futures, what interests it can satisfy. That all says breadth, with enough depth to see what is in store later. And this sounds like the right recipe for someone who is taking a single AS year of physics to broaden their A-level experience. It must also be attractive. A way forward is shown by the Salters - Horners course, attracting interest through leading from applications. Why does that work? It gives physics a story to tell, into which ideas fit and make sense. Our own new A-level, Advancing Physics, must also have interesting stories to tell, which must in addition build up an honest picture of physics. An example: teach electric circuits through modern sensing devices. Sensor instrumentation is a key activity of physicists, full of new ideas, but also simple. It makes essential use of circuits such as the potential divider. Practical work gets better things to do than checking the equation for resistors in parallel

  19. Post-16 update

    NASA Astrophysics Data System (ADS)

    1999-07-01

    (post16) Faces of Physics To study a physics course post-16 is take out an option on your future. But physics itself is very varied, and so is what you might do with it. It seems right that post-16 physics courses reflect important aspects of this variety. Physics varies with why people do it. As reliable knowledge, physics is often essential to making things happen. This is physics as feeding into technology, and quite often feeding off technology. The human urge here is the urge to create things that work. It drives individual inventors; it drives large teams in multinational companies. At the opposite end of this spectrum is physics driven by curiosity, by the urge to find out. The stock examples are the grand discoveries from the expansion of the universe to the discovery of the nucleus of atoms. But the physicist's curiosity is often on a more detailed, even finicky scale: how exactly do the molecules of this polymer respond to stress?; just how do ions implanted in this material modify its conductivity? It is clear to me that a decent post-16 physics course must respect and reflect both. This is by no means a matter of `basic laws and their applications'. It is a matter of recognizing two fundamental interests, in doing and in explaining, and of recognizing that they are at once closely interdependent and worlds apart. Ideas in physics are also not of one kind. One opposition is the idea of describing Nature in terms of deterministic physical laws, as against describing Nature as the predictable outcome of probabilistic behaviour `underneath'. The first has gripped the Western imagination since at least the time of Descartes. The second has increasingly come to the fore, especially in thermodynamics with the idea that we can only make processes work by fixing the circumstances so that uncaring atoms and molecules happen by chance to do what we want. Now in quantum theory both ideas - determinism and randomness - co-exist. Post-16 physics courses are not in

  20. IVGEN Post Flight Analysis

    NASA Technical Reports Server (NTRS)

    Mcquillen, John; Brown, Dan; Hussey, Sam; Zoldak, John

    2014-01-01

    The Intravenous Fluid Generation (IVGEN) Experiment was a technology demonstration experiment that purified ISS potable water, mixed it with salt, and transferred it through a sterilizing filter. On-orbit performance was verified as appropriate and two 1.5 l bags of normal saline solution were returned to earth for post-flight testing by a FDA certified laboratory for compliance with United States Pharmacopiea (USP) standards. Salt concentration deviated from required values and an analysis identified probable causes. Current efforts are focused on Total Organic Content (TOC) testing, and shelf life.The Intravenous Fluid Generation (IVGEN) Experiment demonstrated the purification of ISS potable water, the mixing of the purified water with sodium chloride, and sterilization of the solution via membrane filtration. On-orbit performance was monitored where feasible and two 1.5-liter bags of normal saline solution were returned to earth for post-flight testing by a FDA-registered laboratory for compliance with United States Pharmacopeia (USP)standards [1]. Current efforts have been focused on challenge testing with identified [2] impurities (total organic-carbon), and shelf life testing. The challenge testing flowed known concentrations of contaminants through the IVGEN deionizing cartridge and membrane filters to test their effectiveness. One finding was that the filters and DI-resin themselves contribute to the contaminant load during initial startup, suggesting that the first 100 ml of fluid be discarded. Shelf life testing is ongoing and involves periodic testing of stored DI cartridges and membrane filters that are capped and sealed in hermetic packages. The testing is conducted at six month intervals measuring conductivity and endotoxins in the effluent. Currently, the packaging technique has been successfully demonstrated for one year of storage testing. The USP standards specifies that the TOC be conducted at point of generation as opposed to point of

  1. Recovery post ICU.

    PubMed

    Jones, Christina

    2014-10-01

    Many ICU patients struggle to recovery following critical illness and may be left with physical, cognitive and psychological problems, which have a negative impact on their quality of life. Gross muscle mass loss and weakness can take some months to recover after the patients' Intensive Care Unit (ICU) discharge, in addition critical illness polyneuropathies can further complicate physical recovery. Psychological problems such as anxiety, depression and post traumatic stress disorder (PTSD) are common and have an negative impact on the patients' ability to engage in rehabilitation after ICU discharge. Finally cognitive deficit affecting memory can be a significant problem. The first step in helping patients to recover from such a devastating illness is to recognise those who have the greatest need and target interventions. Research now suggests that there are interventions that can accelerate physical recovery and reduce the incidence of psychological problems such as anxiety, depression and PTSD. Cognitive rehabilitation, however, is still in its infancy. This review will look at the research into patients' recovery and what can be done to improve this where needed.

  2. [POST MORTEM PATERNITY].

    PubMed

    Marguénaud, Jean-Pierre

    2015-07-01

    Post mortem paternity, namely the procreation after the death of the man whom is part of the couple, is one of the questions which raised the most hesitations since the first bioethics laws of 1994. The National Assembly, encouraged by several opinions of the CCNE (National advisory committee of ethics) had let itself convince that the transfer had, at least, to be authorized in utero embryos preserved at the regard of which no one could not claim to have rights equal or higher than those of the woman concerned. However, the Senate always ended up obtaining the maintenance of an absolute prohibition of posthumous procreation (starting) from the spermatozoids or frozen embryos. This indifference with the cruelty of the application of the law to the women plunged into mourning--based on a paradoxical appreciation of the interest of the child not to be born orphan, and on a not very glorious taking into account of the interest of the Body of notaries not to change its practices--is particularly debatable. One can, nevertheless, try to understand it according to the obsession of the legalization of surrogate motherhood by application of the principle of nondiscrimination which could justify the requests of the men who, thanks to a surrogate mother, would wish to become fathers starting from gametes or embryos taken or created before the death of their wife or partner.

  3. NEWS: Post-16 update

    NASA Astrophysics Data System (ADS)

    Campbell, Peter

    2000-07-01

    post16.gif As a teacher of physics it is very easy to become preoccupied with particulars of courses, or topics or even single concepts. Concerned with imminent student audiences and desired learning outcomes, the daily challenge is to summon satisfactory teaching approaches and resources for the job at hand. For the conscientious teacher, assessment outcomes may too often seem a judgment on our own efforts rather than those of our students. From time to time we may step back and think bigger, for example while planning a recruitment event, or while away from work on holiday. We may be successful locally. But why, at a time when books and television documentaries popularizing science have a large following, has physics education been facing declining numbers? Many recognize that physics has an essential contribution to make to the training of science or engineering specialists, but we know that it is also important for the skilled worker, the informed citizen and, in fact, for anyone trying to make sense of the world. So what are the best ways forward for post-16 physics? To make any impact on the bigger picture requires organization, thinking and meeting time among people in diverse roles: teachers and curriculum managers; university lecturers; employers and professional bodies; unitary awarding bodies; regulatory and funding agencies; and even Government. For the past few years, the Institute of Physics post-16 Initiative has created an unrivalled opportunity to address the wider issues. Its Shaping the Future booklets series was designed to stimulate informed discussion and debate, by providing background information and analysis. Taken together, the booklets should help all those concerned with physics education to understand where we are now, and why. Literally dozens of people have contributed to a review and analysis of physics education. Each booklet is a 48-page smorgasbord in A4 landscape format, containing many examples of good practice, basic but

  4. Nuclear Power - Post Fukushima

    NASA Astrophysics Data System (ADS)

    Reyes, Jose, Jr.

    2011-10-01

    The extreme events that led to the prolonged power outage at the Fukushima Daiicchi nuclear plant have highlighted the importance of assuring a means for stable long term cooling of the nuclear fuel and containment following a complete station blackout. Legislative bodies, regulatory agencies and industry are drawing lessons from those events and considering what changes, if any, are needed to nuclear power, post Fukushima. The enhanced safety of a new class of reactor designed by NuScale Power is drawing significant attention in light of the Fukushima events. During normal operation, each NuScale containment is fully immersed in a water-filled stainless steel lined concrete pool that resides underground. The pool, housed in a Seismic Category I building, is large enough to provided 30 days of core and containment cooling without adding water. After 30 days, the decay heat generations coupled with thermal radiation heat transfer is completely adequate to remove core decay heat for an unlimited period of time. These passive power systems can perform their function without requiring an external supply of water of power. An assessment of the NuScale passive systems is being performed through a comprehensive test program that includes the NuScale integral system test facility at Oregon State University

  5. Redefining Post-Secondary Education

    ERIC Educational Resources Information Center

    Turpin, David H.

    2005-01-01

    For at least a brief period of time, the release of Bob Rae's review of post-secondary education in Ontario served to focus public attention on the importance of post-secondary education not only in Ontario, but across Canada. This article elaborates further on Rae's review which stresses the crucial importance of the higher studies and recommends…

  6. Post-Baccalaureate Fellowship Program.

    ERIC Educational Resources Information Center

    Cadbury, Jr., William E.

    The Post-Baccalaureate Fellowship Program provides an opportunity for students who went to college with inferior preparation to supplement their education by studying for 1 year at an academically demanding liberal arts college before entering graduate or professional school. The post-baccalaureate fellows take regular courses in a program that is…

  7. Post-16 update

    NASA Astrophysics Data System (ADS)

    1999-11-01

    (Post-16 Initiative) Engineering Physics? Many A-level physics students do not go on to study physics. For them physics is a support subject, either just for fun or just for the grade. Where physics is a lead subject some students go on to study physics but many more go on to study engineering. So can we deliberately give some aspects of an A-level course an engineering flavour? Electromagnetism would seem a good place to start. There is a clear `physics' route into this topic, a microscopic forces and fields view of the situation. But do our students really need to look at it this way? All electromagnetic machines are linked magnetic and electric circuits. The design idea is to link these circuits as closely as possible. The electric circuits must be as good as possible, with a high conductivity. The magnetic circuits must be as good as possible, with high permeance. Conductivity depends on area/length. So does permeance. The goodness of an electromagnetic machine (how good it is at its job, which is linking electric and magnetic circuits) scales as the square of its linear dimensions. That means small electromagnetic machines are harder to make, and so the very smallest nanomotors are electrostatic. None of this is new, but many teachers are uncomfortable with it. We are thinking like physicists. Many of our students are not. They deserve us to take the trouble every now and again to encourage them to think a bit differently about a topic, to look at practical ways of discussing design and to give their course an engineering flavour. Philip Britton Coursework in A-level Physics The criteria for the new AS and A-levels have provided the teams developing the specifications with an opportunity to think creatively about how internal assessment is used within post-16 physics courses. Teachers may be concerned that allowing 30% of the marks to be internally assessed will create a burden for them. However, it is possible to look at this in a much more positive light

  8. NEWS: Post-16 update

    NASA Astrophysics Data System (ADS)

    1999-05-01

    (post16) Making physics connect Doesn't Melvyn Bragg do a wonderful job, engaging both scientists and artists in sensitive discussion on Radio 4 about their methods and their purposes? But every week teachers have the chance to show their students that physics is a way of seeing the world that is well-connected with other aspects of knowledge and culture. The stakes are high: students who fail to appreciate this generally choose not to study the subject beyond GCSE. Most students find our preoccupation with technical detail off-putting. Accepting that we have a syllabus to cover, it's still a question of balance. In our teaching we should aim for variety in order to find ways to connect with every student's interests. Also, we can show that we (the nearest embodiment of a physicist some students will experience) are multidimensional and so fully human. Most important, teachers need flexibility to both encourage and respond to student comment and questions. The first booklet in the discussion series Shaping the Future takes up these themes. Rich in ideas for both immediate use and the longer term, it aims to stimulate debate and improve teaching. Copies cost £5.50 including postage and are available from Ingrid Ebeyer, Post-16 Initiative, Institute of Physics, 76 Portland Place, London W1N 3DH. How far is it? This question is asked in many family cars and school minibuses at the start of a journey, and answered by most in terms of hours and minutes rather than miles. What a good idea for introducing a social and historical perspective to a lesson on distance, velocity and time. How far can you actually get in a day? What is the range of human activity? Walking for eight hours will get many people about 25 miles. A pack horse will progress at much the same rate, but fast riding or a coach and team of horses will get further. Motorway driving (when the cones are on holiday) would take you nearly 500 miles. The 05.15 am train from Penzance arrives in Inverness at 7

  9. Reviewing Canadian Post-Secondary Education: Post-Secondary Education Policy in Post-Industrial Canada

    ERIC Educational Resources Information Center

    Kirby, Dale

    2007-01-01

    Since 2004, a number of Canadian provinces have initiated comprehensive reviews of their respective public post-secondary education systems. This paper examines the ways in which these provincial post-secondary education reviews are consistent with the pervasive influence of economic globalization on higher education and a more market-driven and…

  10. Post-16 update

    NASA Astrophysics Data System (ADS)

    1999-03-01

    Post-16 Initiative logo Physics in Mathematical Mood Later this year, as part of the post-16 initiative of the Institute of Physics, a booklet with the above title will be published. In draft form, the booklet was discussed at the ASE conference in January. Some of the issues raised are briefly set out here. If you have any views to contribute, please write to Simon Carson at the Institute of Physics or e-mail simon.carson@physics.org. A mathematical view of the world is intrinsically a part of physics and therefore physics should be studied in an appropriately mathematical way. However, we all know that, to some students at least, mathematics proves to be a stumbling block rather than a powerful aid to understanding. So how can we help? Realizing that as physics teachers we need to deliver the mathematics necessary to an understanding of our subject is a start. Its corollary is that we need to find the space within the physics core. We may wish to use supplementary courses such as AS mathematics or QCA's new free-standing mathematics units, but requiring additional courses as a prerequisite to a study of A-level physics may deter students. Teaching the mathematics in context may aid understanding but we also must ensure that techniques are seen in a variety of contexts and that at some point the tool is abstracted from the background. As teachers we need to be aware of the very basic mathematical difficulties that students bring with them: the use of calculators, standard form, simple algebraic manipulation, for example. Mathematical arguments need to be developed fully and carefully. Encouraging cooperation and discussion between students may help the less able to understand and the more able to appreciate and develop their own understanding through making explicit their reasoning by explaining it to others. And what of new technology? Software tools allow students to develop their understanding about graphs, for example, enabling them to investigate the

  11. Coagulopathy post peritoneovenous shunt.

    PubMed Central

    LeVeen, H H; Ip, M; Ahmed, N; Hutto, R B; LeVeen, E G

    1987-01-01

    In 1942, 53% of medically treated patients with cirrhosis were dead 6 months after the onset of ascites. Only 30% survived 1 year. This dismal outlook has improved only slightly with advances in medicine. Yet, some internists reject the peritoneovenous shunt (PVS) for this fatal condition even if they are aware that a diminished blood volume causes the abnormal sodium retention responsible for ascites. Their objections are based on life-threatening complications of PVS, especially post shunt coagulopathy (PSC). Blood shed into the peritoneal cavity becomes incoagulable. Such blood is immediately coagulated by a protocoagulant (soluble collagen) and concurrently lysed by tissue plasminogen activator (TPA) secreted by the peritoneal serosa. Wide zones of lysis surround peritoneal tissue placed on fibrin plates. Large volumes of ascitic fluid infused into circulating blood simulates the fate of blood shed into the peritoneal cavity with lysis playing the major role. Addition of ascitic fluid to normal platelet-rich plasma in vitro initiates clot lysis on thromboelastogram (TEG). Epsilon-aminocaproic acid (EACA) counteracts this lysis. EACA and clotting factors normalize the TEG and arrest PSC. Disposal of ascitic fluid at surgery prevents or ameliorates PSC. Mild PSC was encountered only twice in 150+ consecutive patients (1.3%) with only one case being clinically significant (0.6%). Severe PSC occurred seven times in 98 early shunt patients whose ascitic fluid was not discarded. Severe PSC requires shunt interruption and control of bleeding with clotting factors and EACA. Peritoneal lavage with saline prevents the recurrence of PSC on reopening the shunt. In four patients, EACA and clotting factors were adequate to arrest coagulopathy. Three earlier patients died of PSC before its cause and treatment were understood. Proper management eliminates this life-threatening complication, and PSC cannot be considered a deterrent to PVS. Disseminated intravascular

  12. 32 CFR 643.120 - Post offices.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Post offices. 643.120 Section 643.120 National... Additional Authority of Commanders § 643.120 Post offices. Title 10 U.S.C. 4779b, provides that the SA shall assign suitable space for post office purposes at military posts where post offices have been...

  13. [Post-mortem microbiology analysis].

    PubMed

    Fernández-Rodríguez, Amparo; Alberola, Juan; Cohen, Marta Cecilia

    2013-12-01

    Post-mortem microbiology is useful in both clinical and forensic autopsies, and allows a suspected infection to be confirmed. Indeed, it is routinely applied to donor studies in the clinical setting, as well as in sudden and unexpected death in the forensic field. Implementation of specific sampling techniques in autopsy can minimize the possibility of contamination, making interpretation of the results easier. Specific interpretation criteria for post-mortem cultures, the use of molecular diagnosis, and its fusion with molecular biology and histopathology have led to post-mortem microbiology playing a major role in autopsy. Multidisciplinary work involving microbiologists, pathologists, and forensic physicians will help to improve the achievements of post-mortem microbiology, prevent infectious diseases, and contribute to a healthier population.

  14. Post-tubal sterilization syndrome.

    PubMed

    Lethbridge, D J

    1992-01-01

    This article presents a review of the literature on post-tubal sterilization syndrome. Although studies have shortcomings they suggest the majority of women undergoing tubal sterilization do not experience changes in menstrual patterns after the procedure, but a minority do. Suggestions are made for further research, conducted from a nursing perspective. Implications for practice are suggested, given the tentative information on post-tubal sterilization syndrome.

  15. Post-16 update

    NASA Astrophysics Data System (ADS)

    1999-09-01

    Institute of Physics post-16 initiative, shaping the future Physics education based in IT - sorry ICT! Which, of course, makes for a nifty headline, but as is so often the case with neat slogans, little else. Two formative questions: What, in another decade, will the government of the day call `What you lot should be doing with computers'? and What, of the many things that currently exercise our intellects, will there be anything special to say about in a decade, concerning the use of computers in the teaching of physics? Advancing Physics represents some attempts to come to grips with the second of the two questions above. The first is left to a higher wisdom. In thinking about learning, what can we do with the huge processing power, increasingly available in smaller and less obtrusive packages? What will we do that helps people learn physics, both tomorrow and in 2009? Here are a few suggestions based on development work so far. Wide, reliable and shared access to well ordered learning resources. We have created a CD-ROM, with versions for both student and teacher, that provides a wide range of resources. These do not teach, but do provide. A commitment to allowing a course to evolve and adapt. Electronic publication puts the costs into origination, and not into publication and distribution. A website allows for the community of users to contribute. E-mail networks support individuals and propagate good practice. You can create and explore your own microworlds. The interactive nature of models, and the crafted relationships between the models and the natural world give an insight into the creative imaginary worlds of the physicist. The unreasonable, but pleasurable, success of mathematics in describing the natural world can come to the fore. Measurements that were not possible before are now possible. What was previously indirect, and inaccessible, now becomes a direct measurement, making relationships transparent in new and fruitful ways. The dichotomy between

  16. Post-mortem clinical pharmacology

    PubMed Central

    Ferner, R E

    2008-01-01

    Clinical pharmacology assumes that deductions can be made about the concentrations of drugs from a knowledge of the pharmacokinetic parameters in an individual; and that the effects are related to the measured concentration. Post-mortem changes render the assumptions of clinical pharmacology largely invalid, and make the interpretation of concentrations measured in post-mortem samples difficult or impossible. Qualitative tests can show the presence of substances that were not present in life, and can fail to detect substances that led to death. Quantitative analysis is subject to error in itself, and because post-mortem concentrations vary in largely unpredictable ways with the site and time of sampling, as a result of the phenomenon of post-mortem redistribution. Consequently, compilations of ‘lethal concentrations’ are misleading. There is a lack of adequate studies of the true relationship between fatal events and the concentrations that can be measured subsequently, but without such studies, clinical pharmacologists and others should be wary of interpreting post-mortem measurements. PMID:18637886

  17. Post-operative urinary retention.

    PubMed

    Steggall, Martin; Treacy, Colm; Jones, Mark

    Urinary retention is a common complication of surgery and anaesthesia. The risk of post-operative urinary retention is increased following certain surgical procedures and anaesthetic modalities, and with patients' advancing age. Patients at increased risk of post-operative urinary retention should be identified before surgery or the condition should be identified and treated in a timely manner following surgery. If conservative measures do not help the patient to pass urine, the bladder will need to be drained using either an intermittent catheter or an indwelling urethral catheter, which can result in catheter-associated urinary tract infections. This article provides an overview of normal bladder function, risk factors for developing post-operative urinary retention, and treatment options. Guidance drawn from the literature aims to assist nurses in identifying at-risk patients and inform patient care.

  18. 75 FR 5036 - Proposed Posting, Posting and Deposting of Stockyards

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-01

    .... The document shows the facility number for Shamrock Livestock Commission, Shamrock, Texas is the same... number for Shamrock Livestock Commission, Shamrock, Texas as follows: Stockyard name and Facility number location Date of posting TX-355 Shamrock Livestock November 3, 2003 Commission, Shamrock, Texas. J....

  19. Post-processing of data

    NASA Astrophysics Data System (ADS)

    Pfeifer, Hans-Joachim

    The post processing of Laser Doppler Anemometer (LDA) data has comparable influence on the final results, e.g. reliability, accuracy etc., as well as all the other aspects of LDA instruments. This is due to the fact that signal statistics in LDA are completely different from signal statistics well known in other measuring procedures where the continuous time history of the physical quantity under consideration is available. Four topics are presented: statistical quantities such as mean velocity, turbulence intensity, and histograms; filter control for both counter processors and FFT processors; auto and cross correlation and their Fourier transform; post processing of photon correlograms.

  20. Hydrodynamics of post CHF region

    SciTech Connect

    Ishii, M.; De Jarlais, G.

    1984-04-01

    Among various two-phase flow regimes, the inverted flow in the post-dryout region is relatively less well understood due to its special heat transfer conditions. The review of existing data indicates further research is needed in the areas of basic hydrodynamics related to liquid core disintegration mechanisms, slug and droplet formations, entrainment, and droplet size distributions. In view of this, the inverted flow is studied in detail both analytically and experimentally. Criteria for initial flow regimes in the post-dryout region are given. Preliminary models for subsequent flow regime transition criteria are derived together with correlations for a mean droplet diameter based on the adiabatic simulation data.

  1. Pathophysiology of Post Amputation Pain

    DTIC Science & Technology

    2012-10-11

    ongoing  pain . J  Pain  2003;4:19.  40.  Casey KL. Forebrain mechanisms of  nociception  and  pain : analysis through imaging. Proc Natl  Acad Sci U S A...1    AD_________________ Award Number: W81XWH-11-1-0815 TITLE: Pathophysiology of Post Amputation Pain   PRINCIPAL INVESTIGATOR: Dr. R...25September2012 4. TITLE AND SUBTITLE Pathophysiology of Post Amputation Pain 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-1-0815 5c. PROGRAM

  2. Chaos Theory and Post Modernism

    ERIC Educational Resources Information Center

    Snell, Joel

    2009-01-01

    Chaos theory is often associated with post modernism. However, one may make the point that both terms are misunderstood. The point of this article is to define both terms and indicate their relationship. Description: Chaos theory is associated with a definition of a theory dealing with variables (butterflies) that are not directly related to a…

  3. [Gastrobronchial fistula post sleeve gastrectomy].

    PubMed

    Barboza Besada, Eduardo; Barboza Beraún, Aurelio; Castillo-Ángeles, Manuel; Málaga, Germán; Tan Kuong, Jesús; Valdivia Retamozo, José; Portugal Vivanco, José; Contardo Zambrano, Manuel; Montes, Martín; Kaemena, María Luisa

    2013-01-01

    A 35 years old female with morbid obesity IMC 45 was referred because of a gastrobronchial fistula developed post sleeve gastrectomy initially treated with endoscopic techniques without improvement, reason why a total resection of the gastric remanent with a Roux en Y reconstruction was done as an option with successful result.

  4. STS-80 Post Flight Presentation

    NASA Technical Reports Server (NTRS)

    1996-01-01

    The flight crew of STS-80, Cmdr. Kenneth D. Cockrell, Pilot Kent V. Rominger, Mission Specialists, Tamara E. Jernigan, Thomas D. Jones, and F. Story Musgrave give a post flight presentation of their mission. This presentation is divided into two parts first a slide presentation of still shots, and the second is a video presentation.

  5. Reconsidering Post-Traumatic Stress

    ERIC Educational Resources Information Center

    Berman, Dene S.; Davis-Berman, Jennifer

    2005-01-01

    This article serves to challenge the prevailing wisdom that suggests that most trauma is followed by post-traumatic stress disorder (PTSD), and is best treated with critical incident stress debriefing (CISD). Instead, recent evidence suggests that many individuals exposed to stress do not experience stress responses. Even those who do, however,…

  6. Estonianization Efforts Post-Independence

    ERIC Educational Resources Information Center

    Rannut, Mart

    2008-01-01

    The purpose of this paper is to provide an overview of the sociolinguistic situation in Estonia. The paper opens with a historic overview, followed by an overview of the current demographic situation and of post-Soviet language and education policies and practices. It is argued that Estonia represents a success story in terms of language policy,…

  7. A Post-Occidental Globe?

    ERIC Educational Resources Information Center

    Esen, Huseyin; Sanchez, Alejandra; Araya, Daniel; Gallaga, Drea; Kanogoiw, Fungai; Geary, James; Choe, Keecheng; Ullah, Khan Grogan; Carbajo, Lisa; Fitzpatrick, Margaret; Pour-Previti, Mercedes; Peters, Michael A.; Mukherjee, Mousumi; Britez, Rodrigo

    2012-01-01

    This is an experiment in conversation on the topic of "a post-occidental globe". It emerges from a moderated discussion group where members of a class--master's and PhD students--reflected upon a set of resources provided as part of a course in Global Studies in Education at the University of Illinois. The conversation threads were moderated and…

  8. Post-Lyme disease syndrome.

    PubMed

    Ścieszka, Joanna; Dąbek, Józefa; Cieślik, Paweł

    2015-01-01

    About 10% of patients with Lyme disease continue to experience musculoskeletal pain and cognitive dysfunction after recommended antibiotic treatment. This condition is called post-Lyme disease syndrome (PLDS) or post-treatment Lyme disease syndrome. These two terms are used interchangeably. The pathogenesis of PLDS has been controversial. The hypothesis that patients with PLDS may harbor hidden reservoirs of Borrelia burgdorferi after their initial antibiotic treatment is difficult to accept. The prospective, double-blind studies contradict this point of view. Also, recently published research applying xenodiagnosis to PLDS supports the opinion that PLDS most likely has an autoimmune background. Lengthy courses of antibiotics are not justified in patients with PLDS because of the lack of benefit, and they are fraught with hazards. Most patients with PLDS recover from persistent symptoms with time. However, it can take months before they feel completely well.

  9. Post-Lyme disease syndrome

    PubMed Central

    Dąbek, Józefa; Cieślik, Paweł

    2015-01-01

    About 10% of patients with Lyme disease continue to experience musculoskeletal pain and cognitive dysfunction after recommended antibiotic treatment. This condition is called post-Lyme disease syndrome (PLDS) or post-treatment Lyme disease syndrome. These two terms are used interchangeably. The pathogenesis of PLDS has been controversial. The hypothesis that patients with PLDS may harbor hidden reservoirs of Borrelia burgdorferi after their initial antibiotic treatment is difficult to accept. The prospective, double-blind studies contradict this point of view. Also, recently published research applying xenodiagnosis to PLDS supports the opinion that PLDS most likely has an autoimmune background. Lengthy courses of antibiotics are not justified in patients with PLDS because of the lack of benefit, and they are fraught with hazards. Most patients with PLDS recover from persistent symptoms with time. However, it can take months before they feel completely well. PMID:27407225

  10. The ISAC post-accelerator

    NASA Astrophysics Data System (ADS)

    Laxdal, R. E.; Marchetto, M.

    2014-01-01

    The acceleration chain of the ISAC facility boosts the energy of both radioactive and stable light and heavy ions for beam delivery to both a medium energy area in ISAC-I and a high energy area in ISAC-II. The post-accelerator comprises a 35.4 MHz RFQ to accelerate beams of A/q ≤ 30 from 2 keV/u to 150 keV/u and a post stripper, 106.1 MHz variable energy drift tube linac (DTL) to accelerate ions of A/q ≤ 6 to a final energy between 0.15 MeV/u to 1.5 MeV/u. A 40 MV superconducting linac further accelerates beam from 1.5 MeV/u to energies above the Coulomb barrier. All linacs operate cw to preserve beam intensity.

  11. Pathophysiology of Post Amputation Pain

    DTIC Science & Technology

    2014-12-01

    nociception and pain : analysis through imaging. Proc Natl Acad Sci U S A 1999;96:7668-74. 44. Casey KL, Minoshima S, Morrow TJ, Koeppe RA. Comparison of...trials. Eur J Pain 2006;10:77-88. 95. Dotson RM. Clinical neurophysiology laboratory tests to assess the nociceptive system in humans. J Clin...Award Number: W81XWH-11-1-0815 TITLE: Pathophysiology of Post Amputation Pain PRINCIPAL INVESTIGATOR: Dr. R. Norman Harden CONTRACTING

  12. The SPOOKI post production system

    NASA Astrophysics Data System (ADS)

    Beauchemin, M.; Klasa, M.; Fortier, S.; Fortin, F.; Hardy, G.; Pelletier, L.; Edouard, S.; Archambault, B.; Yazidi, H.

    2010-09-01

    The Canadian Meteorological Centre (CMC) delivers a large number of numerical weather prediction products to the various weather offices and clients throughout Canada and abroad. The current post production system was built according to the needs and ideology of the 1980's and it is becoming obsolete with time. Its cumbersome architecture is difficult to maintain and requires a lot of human and computing resources. The "Weather Elements" section of CMC is aware of the problems associated with its maintenance in the long term and has therefore decided to review in depth the whole approach to the operational post production. The analysis of present and future needs have led to the development of an innovative concept in the operational production field inspired by the "Plug and Play" process. SPOOKI (Système de Production Orienté-Objet contennant une Kyrielle d'Informations - Object oriented production system containing a myriad of information) was created in its present form in 2007. It is based on a modular approach where each plug-in component is specialized, reusable and autonomous. These object oriented programming characteristics greatly simplify the maintenance of the system. Particular attention was also given to create a user-friendly system for novice users. An experimental version of SPOOKI is currently running in development mode and an operational one is planned to be implemented in the coming year. The poster presentation will describe SPOOKI, the future CMC operational post production system. Several examples of usage will be shown.

  13. 76 FR 55425 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-07

    ... informs the public that an appeal of the closing of the Watson, Alabama post office has been filed. It... for review of the Postal Service's determination to close the Watson post office in Watson,...

  14. 42 CFR 124.604 - Posted notice.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... facility shall post notices, which the Secretary supplies in English and Spanish, in appropriate areas of... other than English or Spanish, the facility shall translate the notice into that language and post...

  15. 42 CFR 124.604 - Posted notice.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... facility shall post notices, which the Secretary supplies in English and Spanish, in appropriate areas of... other than English or Spanish, the facility shall translate the notice into that language and post...

  16. 76 FR 58057 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-19

    ... informs the public that an appeal of the closing of the Burnt Prairie, Illinois post office has been filed... for review of the Postal Service's determination to close the Burnt Prairie post office in...

  17. 76 FR 53984 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-30

    ... informs the public that an appeal of the closing of the Prairie Hill, Texas post office has been filed. It... for review of the Postal Service's determination to close the Prairie Hill post office in Prairie...

  18. 76 FR 44385 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-25

    ... informs the public that an appeal of the closing of the Peach Orchard, Arkansas post office has been filed... review of the closing of the Peach Orchard, Arkansas post office. The petition, which was filed...

  19. 42 CFR 124.604 - Posted notice.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... facility shall post notices, which the Secretary supplies in English and Spanish, in appropriate areas of... other than English or Spanish, the facility shall translate the notice into that language and post...

  20. 76 FR 19149 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-06

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Wesleyville Post Office in...

  1. 75 FR 77921 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-14

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice; correction. SUMMARY: The... an appeal of the closing of the Graves Mill, Virginia post office. The procedural schedule...

  2. 76 FR 11824 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-03

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Mitchellville Post Office in...

  3. 77 FR 3806 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-25

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document... Station post office in Yerington, Nevada. The first petition for review received December 28, 2011,...

  4. Protracted refractory pain post-TEVAR: post-implantation syndrome?

    PubMed Central

    Waweru, Peter; Gill, Hardeep; Abeid, Chris

    2016-01-01

    Aortic dissection is a life-threatening condition and has one of the highest mortality rates of cardiovascular diseases. It remains a devastating disease; with multiple unanswered questions concerning treatment modalities. The role of thoracic endovascular aortic repair (TEVAR) in these patients; especially those with uncomplicated acute aortic Type B dissections (AAD-B) is especially controversial although it has been shown to have better long-term outcomes compared to medical therapy alone. For those who have TEVAR, up to 60% may develop an acute, transient systemic inflammatory response syndrome that remains vaguely defined. The role of local inflammation in this post-implantation syndrome (PIS) has not been highlighted. We present a case of a 57-year-old male patient with an uncomplicated AAD-B who developed an ‘atypical’ PIS post-TEVAR with severe refractory abdominal pains; leukocytosis and raised C-reactive protein. The role of local inflammation in PIS is highlighted. PMID:28344762

  5. Post-Tenure Review. SPEC Kit 261.

    ERIC Educational Resources Information Center

    Hook, Sara Anne, Comp.; Lees, N. Doug, Comp.; Powers, Gerald, Comp.

    2000-01-01

    This SPEC (Systems and Procedures Exchange Center) Kit reports results of a survey of ARL (Association of Research Libraries) that examined post-tenure review of librarians throughout higher education in North America. The purpose of the survey was to identify which institutions apply post-tenure or post-continuing appointment review to library…

  6. 36 CFR 261.51 - Posting.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 36 Parks, Forests, and Public Property 2 2012-07-01 2012-07-01 false Posting. 261.51 Section 261.51 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE PROHIBITIONS Prohibitions in Areas Designated by Order § 261.51 Posting. Posting is accomplished by: (a) Placing a copy...

  7. 76 FR 58314 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-20

    ... informs the public that an appeal of the closing of the Board Camp, Arkansas post office has been filed... for review of the Postal Service's determination to close the Board Camp post office in Board Camp, Arkansas. The petition was filed by the Residents and Customers of Board Camp, Arkansas Post...

  8. 10 CFR 20.1902 - Posting requirements.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... HIGH RADIATION AREA.” (d) Posting of airborne radioactivity areas. The licensee shall post each airborne radioactivity area with a conspicuous sign or signs bearing the radiation symbol and the words “CAUTION, AIRBORNE RADIOACTIVITY AREA” or “DANGER, AIRBORNE RADIOACTIVITY AREA.” (e) Posting of areas...

  9. 10 CFR 20.1902 - Posting requirements.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... HIGH RADIATION AREA.” (d) Posting of airborne radioactivity areas. The licensee shall post each airborne radioactivity area with a conspicuous sign or signs bearing the radiation symbol and the words “CAUTION, AIRBORNE RADIOACTIVITY AREA” or “DANGER, AIRBORNE RADIOACTIVITY AREA.” (e) Posting of areas...

  10. 10 CFR 20.1902 - Posting requirements.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... HIGH RADIATION AREA.” (d) Posting of airborne radioactivity areas. The licensee shall post each airborne radioactivity area with a conspicuous sign or signs bearing the radiation symbol and the words “CAUTION, AIRBORNE RADIOACTIVITY AREA” or “DANGER, AIRBORNE RADIOACTIVITY AREA.” (e) Posting of areas...

  11. 10 CFR 20.1902 - Posting requirements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... HIGH RADIATION AREA.” (d) Posting of airborne radioactivity areas. The licensee shall post each airborne radioactivity area with a conspicuous sign or signs bearing the radiation symbol and the words “CAUTION, AIRBORNE RADIOACTIVITY AREA” or “DANGER, AIRBORNE RADIOACTIVITY AREA.” (e) Posting of areas...

  12. 10 CFR 20.1902 - Posting requirements.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... HIGH RADIATION AREA.” (d) Posting of airborne radioactivity areas. The licensee shall post each airborne radioactivity area with a conspicuous sign or signs bearing the radiation symbol and the words “CAUTION, AIRBORNE RADIOACTIVITY AREA” or “DANGER, AIRBORNE RADIOACTIVITY AREA.” (e) Posting of areas...

  13. 10 CFR 160.6 - Posting.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 2 2014-01-01 2014-01-01 false Posting. 160.6 Section 160.6 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) TRESPASSING ON COMMISSION PROPERTY § 160.6 Posting. Notices stating the pertinent prohibitions of §§ 160.3 and 160.4 and penalties of § 160.5 will be conspicuously posted at all entrances...

  14. Post-Colonial Theory and Action Research

    ERIC Educational Resources Information Center

    Parsons, Jim B.; Harding, Kelly J.

    2011-01-01

    This essay explores connections between post-colonial theory and action research. Post-colonial theory is committed to addressing the plague of colonialism. Action research, at its core, promises to problematize uncontested "colonial" hegemonies of any form. Both post-colonial theory and action research engage dialogic, critically reflective and…

  15. 37 CFR 2.81 - Post publication.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2012-07-01 2012-07-01 false Post publication. 2.81 Section 2.81 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE RULES OF PRACTICE IN TRADEMARK CASES Publication and Post Publication § 2.81 Post publication....

  16. 37 CFR 2.81 - Post publication.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2013-07-01 2013-07-01 false Post publication. 2.81 Section 2.81 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE RULES OF PRACTICE IN TRADEMARK CASES Publication and Post Publication § 2.81 Post publication....

  17. 37 CFR 2.81 - Post publication.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Post publication. 2.81 Section 2.81 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE RULES OF PRACTICE IN TRADEMARK CASES Publication and Post Publication § 2.81 Post publication....

  18. 37 CFR 2.81 - Post publication.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2011-07-01 2011-07-01 false Post publication. 2.81 Section 2.81 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE RULES OF PRACTICE IN TRADEMARK CASES Publication and Post Publication § 2.81 Post publication....

  19. 37 CFR 2.81 - Post publication.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2014-07-01 2014-07-01 false Post publication. 2.81 Section 2.81 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE RULES OF PRACTICE IN TRADEMARK CASES Publication and Post Publication § 2.81 Post publication....

  20. Pain Management: Post-Amputation Pain

    MedlinePlus

    Pain Management Post-Amputation Pain Volume 8 · Issue 2 · March/April 1998 Text size Larger text Smaller text Java Required Print page Save and share ... by G. Edward Jeffries, MD, FACS Post-Amputation Pain Post-amputation pain is one of the most ...

  1. 39 CFR 241.1 - Post offices.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Post offices. 241.1 Section 241.1 Postal Service... DISCONTINUANCE § 241.1 Post offices. (a) Establishment. See § 113.1 of this chapter. (b) Classification. As of July 1 each year, post offices are classified by the Postmaster General based on the allowable...

  2. 75 FR 54192 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-03

    ...] [FR Doc No: 2010-22040] POSTAL REGULATORY COMMISSION [Docket No. A2010-5; Order No. 526] Post Office... that an appeal of the closing of the Rentiesville Post Office, Rentiesville, Oklahoma 74459 has been... closing of the Rentiesville Post Office, Rentiesville, Oklahoma 74459. The appeal, postmarked August...

  3. 39 CFR 241.1 - Post offices.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 39 Postal Service 1 2012-07-01 2012-07-01 false Post offices. 241.1 Section 241.1 Postal Service UNITED STATES POSTAL SERVICE ORGANIZATION AND ADMINISTRATION ESTABLISHMENT CLASSIFICATION, AND DISCONTINUANCE § 241.1 Post offices. (a) Establishment. Post Offices are established and maintained at...

  4. STS-112 Post Flight Presentation

    NASA Technical Reports Server (NTRS)

    2002-01-01

    The STS-112 post flight presentation begins with a shot of the moonrise over the Earth's Limb. A photograph of the STS-112 crew is shown. The crew consists of Mission Specialists Sandy Magnus, David Wolf, Piers Sellers and Fodor Yurchikhin, Pilot Pam Melroy and Commander Jeff Ashby. The crew departs from the Operations and Control Building to the launch pad at Kennedy Space Center in Florida. Sandy Magnus is shown preparing to board the Space Shuttle Atlantis. The actual STS-112 launch with flight deck activity during rendezvous with the International Space Station is also presented.

  5. Hyperbaric post weld heat treatment

    SciTech Connect

    Saunderson, S.; Waller, D.

    1983-05-01

    This paper describes a sub-sea hyperbaric Post Weld Heat Treatment (PWHT) system developed jointly by SHELL UK EXPLORATION and PRODUCTION and COMEX DIVING. It discusses: assessment of power requirements and equipment, initial tests conducted in the COMEX hydrosphere and in shallow water in Marseille, and full scale North Sea trials at - 150 m, comparing the performance and results of two separate power sources and control units. Particular attention is drawn to the importance of the elements, insulation and controls used to achieve uniform distribution of heat at the required temperature in a HELIOX environment.

  6. In vitro evaluation of glass fiber post

    PubMed Central

    Sharma, Navneet; Singh, Harpal

    2012-01-01

    Statement of problem: Techniques and recommendations for the restoration of endodontically treated teeth have changed from the use of custom cast metal post and core system to glass fiber-reinforced (GFRC) post and composite core system. Has this latest prefabricated glass fiber reinforced post and composite core system increased the fracture resistance of teeth and reduced the incidence of unrestorable root fractures. Purpose: The purpose of this study was to evaluate the incidence of root fracture and mode of failure of endodontically treated teeth restored with two different post and core systems. Material and Methods: Forty maxillary central incisors were randomly divided into two groups. (n=20). All teeth received endodontic treatment. First group was restored with custom cast post and core system. Second group was restored with glass fiber post and composite core system. In Both the groups posts were cemented with adhesive resin cement. Compressive load was applied at an angle of 130 to the long axis of teeth at a cross head speed of 1 mm/min until fracture occurred. Data were analyzed with student “t” test P<.001. Results: The mean value for fracture resistance was (331.4025) N in Group -I Custom cast Ni-Cr post and core and (237.0625) N in Group -II Glass fiber reinforced post and composite core system. Students “t” test shows the significant difference in fracture resistance of two groups. Conclusion: This study showed that the incidence of root fracture was significantly higher in custom cast Ni-Cr post and core system than glass fiber post and composite core system. A more favourable mode of failure was observed in teeth restored with Group II glass fiber post system. Key words:Post-and-core technique, glass fiber post, cast post and-core system, fracture resistance, endodontically treated teeth. PMID:24558556

  7. Post-Secularism, Religious Knowledge and Religious Education

    ERIC Educational Resources Information Center

    Carr, David

    2012-01-01

    Post-secularism seems to follow in the wake of other (what are here called) "postal" perspectives--post-structuralism, postmodernism, post-empiricism, post-positivism, post-analytical philosophy, post-foundationalism and so on--in questioning or repudiating what it takes to be the epistemic assumptions of "modernism." To be sure, post-secularism…

  8. Sterile post-traumatic immunosuppression

    PubMed Central

    Islam, Md Nahidul; Bradley, Benjamin A; Ceredig, Rhodri

    2016-01-01

    After major trauma, the human immune system initiates a series of inflammatory events at the injury site that is later followed by suppression of local inflammation favoring the repair and remodeling of the damaged tissues. This local immune response involves complex interactions between resident cells such as macrophages and dendritic cells, soluble mediators such as cytokines and chemokines, and recruited cells such as neutrophils, monocytes and mesenchymal stromal cells. If of sufficient magnitude, these initial immune responses nevertheless have systemic consequences resulting in a state called post-traumatic immunosuppression (PTI). However, controversy exists regarding the exact immunological changes occurring in systemic compartments triggered by these local immune responses. PTI is one of the leading causes of post-surgical mortality and makes patients vulnerable to hospital-acquired infections, multiple organ failure and many other complications. In addition, hemorrhage, blood transfusion, immunesenescence and immunosuppressant drugs aggravate PTI. PTI has been intensively studied, but published results are frequently cloudy. The purpose of this review is to focus on the contributions made by different responsive modalities to immunosuppression following sterile trauma and to try to integrate these into an overall scheme of PTI. PMID:27195120

  9. Parameterized post-Newtonian cosmology

    NASA Astrophysics Data System (ADS)

    Sanghai, Viraj A. A.; Clifton, Timothy

    2017-03-01

    Einstein’s theory of gravity has been extensively tested on solar system scales, and for isolated astrophysical systems, using the perturbative framework known as the parameterized post-Newtonian (PPN) formalism. This framework is designed for use in the weak-field and slow-motion limit of gravity, and can be used to constrain a large class of metric theories of gravity with data collected from the aforementioned systems. Given the potential of future surveys to probe cosmological scales to high precision, it is a topic of much contemporary interest to construct a similar framework to link Einstein’s theory of gravity and its alternatives to observations on cosmological scales. Our approach to this problem is to adapt and extend the existing PPN formalism for use in cosmology. We derive a set of equations that use the same parameters to consistently model both weak fields and cosmology. This allows us to parameterize a large class of modified theories of gravity and dark energy models on cosmological scales, using just four functions of time. These four functions can be directly linked to the background expansion of the universe, first-order cosmological perturbations, and the weak-field limit of the theory. They also reduce to the standard PPN parameters on solar system scales. We illustrate how dark energy models and scalar-tensor and vector-tensor theories of gravity fit into this framework, which we refer to as ‘parameterized post-Newtonian cosmology’ (PPNC).

  10. [Post-Lyme disease syndrome].

    PubMed

    Błaut-Jurkowska, Justyna; Jurkowski, Marcin

    2016-02-01

    Lyme disease is a chronic infectious disease caused by the bacteria, spirochete of the Borrelia type. Skin, nervous system, musculoskeletal system and heart may be involved in the course of the disease. The prognosis for properly treated Lyme disease is usually good. However, in about 5% of patients so called Post-Lyme disease syndrome (PLSD) develops. It is defined as a syndrome of subjective symptoms persisting despite proper treatment of Borrelia burgdorferi infection. The most common symptoms include: fatigue, muscle and joint pain, and problems with memory and concentration. Pathogenesis of PLDS remains unknown. The differential diagnosis should include neurological, rheumatic and mental diseases. Till now there is no causative treatment of PLDS. In relieving symptom rehabilitation, painkillers, anti-inflammatory and antidepressants medicines are recommended. Emotional and psychological supports are also necessary. Non-specific symptoms reported by patients with post- Lyme disease syndrome raise the suspicion of other pathologies. This can lead to misdiagnosis and implementation of unnecessary, potentially harmful to the patient's therapy. An increase in tick-borne diseases needs to increase physicians awareness of these issues.

  11. Hot Post-AGB Stars

    NASA Astrophysics Data System (ADS)

    Parthasarathy, M.; Gauba, G.; Fujii, T.; Nakada, Y.

    2001-08-01

    From the study of IRAS sources with far-IR colors similar to planetary nebulae (PNe), several proto-planetary nebulae with hot (OB) post-AGB central stars have been detected. These stars form an evolutionary link between the cooler G,F,A supergiant stars that have evolved off the Asymptotic Giant Branch (AGB) and the hot (OB) central stars of PNe. The optical spectra of these objects show strong Balmer emission lines and in some cases low excitation nebular emission lines such as [NII] and [SII] superposed on the OB stellar continuum. The absence of of [OIII] 5007Å line and the presence of low excitation nebular emission lines indicate that photoionisation has just started. The UV(IUE) spectra of some of these objects revealed violet shifted stellar wind P-Cygni profiles of CIV, SiIV and NV, indicating hot and fast stellar wind and post-AGB mass loss. These objects appear to be rapildy evolving into the early stages of PNe similar to that observed in the case of Hen1357 IRAS 17119-5926 (Stingray Nebula) and IRAS 18062+2410 SAO85766.

  12. An SEM Approach for the Evaluation of Intervention Effects Using Pre-Post-Post Designs

    ERIC Educational Resources Information Center

    Mun, Eun Young; von Eye, Alexander; White, Helene R.

    2009-01-01

    This study analyzes latent change scores using latent curve models (LCMs) for evaluation research with pre-post-post designs. The article extends a recent article by Willoughby, Vandergrift, Blair, and Granger (2007) on the use of LCMs for studies with pre-post-post designs, and demonstrates that intervention effects can be better tested using…

  13. [Post-tubal ligation syndrome].

    PubMed

    Satoh, K; Osada, H

    1993-01-01

    Post-tubal ligation syndrome includes pain during intercourse, aching lower back, premenstrual tension syndrome, difficulty in menstruating, uterine hemorrhage, and absence of menstruation. The syndrome is caused by blood circulation problems in and around the Fallopian tubes and ovaries, pressure on nerves, and intrapelvic adhesion. Differentiating between this syndrome and endometritis during diagnosis and differentiating between functional hemorrhage due to hormonal abnormality and anatomical hemorrhage due to polyp or tumor is very important. Since the symptoms of this syndrome are mild, simple symptomatic treatment is sufficient in most cases. In some cases, however, desquamation surgery or reversal of tubal ligation may be necessary. Endoscopic surgery is also available. In Japan, because of widespread use of condoms and IUDs, tubal ligation is not very common.

  14. Post-Newtonian quasirigid body

    NASA Astrophysics Data System (ADS)

    Xu, Chongming; Tao, Jin-He; Wu, Xuejun

    2004-01-01

    In this paper, we construct for the first time, in the first post-Newtonian (1PN) approximation, a complete model of a quasirigid body by means of a new constraint on the mass current density and mass density. In our 1PN quasirigid body model most of the relations, such as the spin vector proportional to the angular velocity, the definition of the moment of inertia tensor, the key relation between the mass quadrupole moment and the moment of inertia tensor, the rigid rotating formulas for the mass quadrupole moment, and the moment of inertia tensor, are just an extension of the main relations in the Newtonian rigid body model. When all of the 1/c2 terms are neglected, the 1PN quasirigid body model and the corresponding formulas reduce to the Newtonian version. A key relation is obtained in this paper for the first time, which might be very useful in future applications to problems in geodynamics and astronomy.

  15. [Fiber reinforced composite posts: literature review].

    PubMed

    Frydman, G; Levatovsky, S; Pilo, R

    2013-07-01

    FRC (Fiber-reinforced composite) posts have been used since the beginning of the 90s with the introduction of carbon fiber posts. Fiber posts are widely used to restore endodontically treated teeth that have insufficient coronal tooth structure. Many in vitro and in vivo studies have shown the advantage of using FRC over prefabricated and cast metal post especially indicated in narrow root canals which are prone to vertically root fracture. The most frequent failure of FRC is debonding of a post at the resin cement/dentin interface. Bonding to dentin may be achieved by using etch-and-rinse and self-etch adhesives. The bond strength formed by self-adhesive cements is noticeably lower in comparison to the bond strength formed with resin cements applied in combination with etch-and-rinse adhesives. In an attempt to maximize resin bonding to fiber posts, several surface treatments have been suggested. Sandblasting with alumina particles results in an increased surface roughness and surface area without affecting the integrity of the post as long as it is applied by 50 microm alumina particles at 2.5 bars for maximally 5 seconds at a distance of 30 mm. The efficiency of post salinization is controversial and its contribution to the retention is of minor importance. Hydrofluoric acid has recently been proposed for etching glass fiber posts but this technique produced substantial damage to the glass fibers and affected the integrity of the post. Delayed cementation of fiber post (at least 24h post endodontic treatment) resulted in higher retentive strengths in comparison to immediate cementation and the best results were obtained when the luting agent was brought into the post space with lentulo spirals or specific syringes. The resin cement film thickness also influences the pullout strengths of fiber-reinforced posts .The highest bond strength values were obtained when the cement layer oversized the post spaces but not larger than 0.3 mm. The use of core build

  16. Abnormal erythroid cell proliferation and myelofibrosis in a cat.

    PubMed

    Iwanaga, Tomoko; Miura, Naoki; Miyoshi, Noriaki; Endo, Yasuyuki; Momoi, Yasuyuki

    2012-07-01

    A cat was presented with severe progressive anemia despite marked erythroblastosis. The cat was negative for feline leukemia virus antigen and feline immunodeficiency virus antibody. Bone marrow cytology revealed an excess of erythroid cells with a predominance of prorubricytes and basophilic rubricytes. No response to immunosuppressive therapy was obtained, and a tentative diagnosis of myelodysplastic syndrome was made. The cat showed a partial response to low-dose cytarabine (20 mg/m(2) subcutaneously q24) but died 51 days after the 1st admission. Histopathological examination revealed fibrosis in the bone marrow and marked infiltration of erythroid cells into other organs.

  17. Reactivation of Pulmonary Tuberculosis following Treatment of Myelofibrosis with Ruxolitinib.

    PubMed

    Abidi, Maheen Z; Haque, Javeria; Varma, Parvathi; Olteanu, Horatiu; Guru Murthy, Guru Subramanian; Dhakal, Binod; Hari, Parameswaran

    2016-01-01

    Ruxolitinib is widely in use for treatment of myeloproliferative disorders. It causes inhibition of the Janus kinase (JAK) signal transducer and activation of transcription (STAT) pathway, which plays a key role in the underlying pathophysiology of myeloproliferative diseases. We describe a case of reactivation pulmonary tuberculosis in a retired physician while on treatment with ruxolitinib. We also review the literature on opportunistic infections following use of ruxolitinib. Our case highlights the importance of screening for latent tuberculosis in patients from highly endemic areas prior to start of therapy with ruxolitinib.

  18. Reactivation of Pulmonary Tuberculosis following Treatment of Myelofibrosis with Ruxolitinib

    PubMed Central

    Haque, Javeria; Varma, Parvathi; Guru Murthy, Guru Subramanian; Dhakal, Binod; Hari, Parameswaran

    2016-01-01

    Ruxolitinib is widely in use for treatment of myeloproliferative disorders. It causes inhibition of the Janus kinase (JAK) signal transducer and activation of transcription (STAT) pathway, which plays a key role in the underlying pathophysiology of myeloproliferative diseases. We describe a case of reactivation pulmonary tuberculosis in a retired physician while on treatment with ruxolitinib. We also review the literature on opportunistic infections following use of ruxolitinib. Our case highlights the importance of screening for latent tuberculosis in patients from highly endemic areas prior to start of therapy with ruxolitinib. PMID:27843657

  19. [Post-traumatic stress disorder after childbirth].

    PubMed

    Korábová, I; Masopustová, Z

    2016-01-01

    The aim of this paper is to introduce the issue of post-traumatic stress disorder after childbirth to health care professionals. The text focuses on the diagnostic definition of post-traumatic stress disorder after childbirth, symptoms, physiological background, prevalence, course, risk factors and consequences of post-traumatic stress disorder after childbirth for a woman, her child and her partner. Options for interventions and therapy are outlined as well.

  20. The Management of Post-Term Pregnancy

    PubMed Central

    Iwanicki, Stanislaw; Akierman, Albert

    1988-01-01

    Although post-term pregnancy is associated with an increased incidence of fetal distress, oligohydramnios, fetal macrosomia, fetal dysmaturity, and perinatal mortality, as many as 80% of post-term fetuses appear completely normal. The authors of this article discuss the three sub-groups of post-term pregnancies, and deal with the diagnosis and antepartum and intrapartum management of the condition. Recommendations and a protocol for management are provided. PMID:21253236

  1. MRO DKF Post-Processing Tool

    NASA Technical Reports Server (NTRS)

    Ayap, Shanti; Fisher, Forest; Gladden, Roy; Khanampompan, Teerapat

    2008-01-01

    This software tool saves time and reduces risk by automating two labor-intensive and error-prone post-processing steps required for every DKF [DSN (Deep Space Network) Keyword File] that MRO (Mars Reconnaissance Orbiter) produces, and is being extended to post-process the corresponding TSOE (Text Sequence Of Events) as well. The need for this post-processing step stems from limitations in the seq-gen modeling resulting in incorrect DKF generation that is then cleaned up in post-processing.

  2. Postpartum Post-Traumatic Stress Disorder

    MedlinePlus

    ... Depression During Pregnancy & Postpartum Anxiety During Pregnancy & Postpartum Pregnancy or Postpartum Obsessive Symptoms Postpartum Post-Traumatic Stress Disorder Bipolar Mood Disorders Postpartum Psychosis Tools for ...

  3. Fabricating fiber-reinforced composite posts.

    PubMed

    Manhart, Jürgen

    2011-03-01

    Endodontic posts do not increase the strength of the remaining tooth structure in endodontically treated teeth. On the contrary, depending on the post design employed (tapered versus parallel-sided), the root can be weakened relative to the amount of tooth removed during preparation. In many cases, if there has been a high degree of damage to the clinical crown, conservative preparation for an anatomic tapered (biomimetic) post with the incorporation of a ferrule on solid tooth structure is necessary to protect the reaming root structure as well as for the long-term retention of the composite resin core and the definitive restoration. Adhesively luted endodontic posts reinforced with glass or quartz fiber lead to better homogeneous tension distribution when loaded than rigid metal or zirconium oxide ceramic posts. Fiber-reinforced posts also possess advantageous optical properties over metal or metal oxide post systems. The clinician should realize that there are admittedly substantial differences in the mechanical loading capacity of the different fiber-reinforced endodontic posts and should be aware of such differences in order to research and select a suitable post system for use.

  4. STS 63: Post Flight Presentation

    NASA Technical Reports Server (NTRS)

    1995-01-01

    At a post flight conference, Captain Jim Wetherbee, of STS Flight 63, introduces each of the other members of the STS 63 crew (Eileen Collins, Pilot; Dr. Bernard Harris, Payload Commander; Dr. Michael Foale, Mission Specialist from England; Dr. Janice Voss, Misssion Specialist; and Colonel Vladimir Titor, Misssion Specialist from Russia. A short biography of each member and a brief description of their assignment during this mission is given. A film was shown that included the preflight suit-up, a view of the launch site, the actual night launch, a tour of the Space Shuttle and several of the experiment areas, several views of earth and the MIR Space Station and cosmonauts, the MIR-Space Shuttle rendezvous, the deployment of the Spartan Ultraviolet Telescope, Foale and Harris's EVA and space walk, the retrieval of Spartan, and the night entry home, including the landing. Several spaceborne experiments were introduced: the radiation monitoring experiment, environment monitoring experiment, solid surface combustion experiment, and protein crystal growth and plant growth experiments. This conference ended with still, color pictures, taken by the astronauts during the entire STS 63 flight, being shown.

  5. Carbohydrate post-glycosylational modifications

    PubMed Central

    Yu, Hai; Chen, Xi

    2008-01-01

    Carbohydrate modification is a common phenomenon in nature. Many carbohydrate modifications such as some epimerization, O-acetylation, O-sulfation, O-methylation, N-deacetylation, and N-sulfation, take place after the formation of oligosaccharide or polysaccharide backbones. These modifications can be categorized as carbohydrate post-glycosylational modifications (PGMs). Carbohydrate PGMs further extend the complexity of the structures and the synthesis of carbohydrates and glycoconjugates. They also increase the capacity of the biological information that can be controlled by finely tuning the structures of carbohydrates. Developing efficient methods to obtain structurally defined naturally occurring oligosaccharides, polysaccharides, and glycoconjugates with carbohydrate PGMs is essential for understanding the biological significance of carbohydrate PGMs. Combine with high-throughput screening methods, synthetic carbohydrates with PGMs are invaluable probes in structure-activity relationship studies. We illustrate here several classes of carbohydrates with PGMs and their applications. Recent progress in chemical, enzymatic, and chemoenzymatic syntheses of these carbohydrates and their derivatives are also presented. PMID:17340000

  6. STS-113 Post Flight Presentation

    NASA Technical Reports Server (NTRS)

    2002-01-01

    The STS-113 post-flight presentation begins with a view of Mission Specialists Michael E. Lopez-Alegria and John B. Herrington getting suited for the space mission. The STS-113 crew consists of: Commander James D. Wetherbee, Pilot Paul Lockhart, Mission Specialists Michael Lopez-Alegria and John Herrington. Cosmonauts Valery Korzun, and Sergei Treschev, and astronaut Peggy Whitson who are all members of the expedition five crew, and Commander Kenneth Bowersox, Flight Engineers Nikolai Budarin and Donald Pettit, members of Expedition Six. The main goal of this mission is to take Expedition Six up to the International Space Station and Return Expedition Five to the Earth. The second objective is to install the P(1) Truss segment. Three hours prior to launch, the crew of Expedition Six along with James Wetherbee, Paul Lockhart, Michael Lopez-Alegria and John Herrington are shown walking to an astrovan, which takes them to the launch pad. The actual liftoff is presented. Three Extravehicular Activities (EVA)'s are performed on this mission. Michael Lopez-Alegria and John Herrington are shown performing EVA 1 and EVA 2 which include making connections between the P1 and S(0) Truss segments, and installing fluid jumpers. A panoramic view of the ISS with the Earth in the background is shown. The grand ceremony of the crew exchange is presented. The astronauts performing everyday duties such as brushing teeth, washing hair, sleeping, and eating pistachio nuts are shown. The actual landing of the Space Shuttle is presented.

  7. Post orgasmic illness syndrome (POIS)

    PubMed Central

    2016-01-01

    Men with post orgasmic illness syndrome (POIS) become ill rather immediately after ejaculation, whether spontaneously at night, during sexual intercourse or masturbation. Two subtypes are distinguished: primary and secondary POIS. It also occurs before or after a man has been sterilized. POIS is an invalidating most probably auto-immune disease leading to much distress in males and their partners. It is characterized by five criteria. Its symptoms are described by seven clusters. However, the manifestation of these symptoms varies from one male to the other but is relatively constant in the person himself. Among men the symptoms vary in intensity, durations and sort of symptoms. POIS is a chronic disorder that manifests itself in POIS “attacks” that occur within a few minutes to a few hours after ejaculation, and disappear spontaneously after 3 to 7 days. POIS is not associated with increased total serum IgE concentrations. On the contrary, there are indications that POIS is triggered by specific cytokines that are released by an auto-immune reaction to the man’s seminal fluid. Indirect clinical evidence suggests that the antigen (Ag) triggering the POIS systemic reaction is not bound to spermatozoa but to seminal fluid produced by prostatic tissue. In addition, POIS may also occur—although rarely—in females. In those cases, it is hypothesized that the Ag is associated with female prostatic tissue around the vagina. PMID:27652231

  8. Post orgasmic illness syndrome (POIS).

    PubMed

    Waldinger, Marcel D

    2016-08-01

    Men with post orgasmic illness syndrome (POIS) become ill rather immediately after ejaculation, whether spontaneously at night, during sexual intercourse or masturbation. Two subtypes are distinguished: primary and secondary POIS. It also occurs before or after a man has been sterilized. POIS is an invalidating most probably auto-immune disease leading to much distress in males and their partners. It is characterized by five criteria. Its symptoms are described by seven clusters. However, the manifestation of these symptoms varies from one male to the other but is relatively constant in the person himself. Among men the symptoms vary in intensity, durations and sort of symptoms. POIS is a chronic disorder that manifests itself in POIS "attacks" that occur within a few minutes to a few hours after ejaculation, and disappear spontaneously after 3 to 7 days. POIS is not associated with increased total serum IgE concentrations. On the contrary, there are indications that POIS is triggered by specific cytokines that are released by an auto-immune reaction to the man's seminal fluid. Indirect clinical evidence suggests that the antigen (Ag) triggering the POIS systemic reaction is not bound to spermatozoa but to seminal fluid produced by prostatic tissue. In addition, POIS may also occur-although rarely-in females. In those cases, it is hypothesized that the Ag is associated with female prostatic tissue around the vagina.

  9. Post-transplant lymphoproliferative disorders.

    PubMed

    Dharnidharka, Vikas R; Webster, Angela C; Martinez, Olivia M; Preiksaitis, Jutta K; Leblond, Veronique; Choquet, Sylvain

    2016-01-28

    Post-transplant lymphoproliferative disorders (PTLDs) are a group of conditions that involve uncontrolled proliferation of lymphoid cells as a consequence of extrinsic immunosuppression after organ or haematopoietic stem cell transplant. PTLDs show some similarities to classic lymphomas in the non-immunosuppressed general population. The oncogenic Epstein-Barr virus (EBV) is a key pathogenic driver in many early-onset cases, through multiple mechanisms. The incidence of PTLD varies with the type of transplant; a clear distinction should therefore be made between the conditions after solid organ transplant and after haematopoietic stem cell transplant. Recipient EBV seronegativity and the intensity of immunosuppression are among key risk factors. Symptoms and signs depend on the localization of the lymphoid masses. Diagnosis requires histopathology, although imaging techniques can provide additional supportive evidence. Pre-emptive intervention based on monitoring EBV levels in blood has emerged as the preferred strategy for PTLD prevention. Treatment of established disease includes reduction of immunosuppression and/or administration of rituximab (a B cell-specific antibody against CD20), chemotherapy and EBV-specific cytotoxic T cells. Despite these strategies, the mortality and morbidity remains considerable. Patient outcome is influenced by the severity of presentation, treatment-related complications and risk of allograft loss. New innovative treatment options hold promise for changing the outlook in the future.

  10. 10 CFR 34.53 - Posting.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Posting. 34.53 Section 34.53 Energy NUCLEAR REGULATORY COMMISSION LICENSES FOR INDUSTRIAL RADIOGRAPHY AND RADIATION SAFETY REQUIREMENTS FOR INDUSTRIAL RADIOGRAPHIC OPERATIONS Radiation Safety Requirements § 34.53 Posting. All areas in which industrial radiography is...

  11. 10 CFR 34.53 - Posting.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Posting. 34.53 Section 34.53 Energy NUCLEAR REGULATORY COMMISSION LICENSES FOR INDUSTRIAL RADIOGRAPHY AND RADIATION SAFETY REQUIREMENTS FOR INDUSTRIAL RADIOGRAPHIC OPERATIONS Radiation Safety Requirements § 34.53 Posting. All areas in which industrial radiography is...

  12. 10 CFR 34.53 - Posting.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 1 2012-01-01 2012-01-01 false Posting. 34.53 Section 34.53 Energy NUCLEAR REGULATORY COMMISSION LICENSES FOR INDUSTRIAL RADIOGRAPHY AND RADIATION SAFETY REQUIREMENTS FOR INDUSTRIAL RADIOGRAPHIC OPERATIONS Radiation Safety Requirements § 34.53 Posting. All areas in which industrial radiography is...

  13. 10 CFR 34.53 - Posting.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Posting. 34.53 Section 34.53 Energy NUCLEAR REGULATORY COMMISSION LICENSES FOR INDUSTRIAL RADIOGRAPHY AND RADIATION SAFETY REQUIREMENTS FOR INDUSTRIAL RADIOGRAPHIC OPERATIONS Radiation Safety Requirements § 34.53 Posting. All areas in which industrial radiography is...

  14. 10 CFR 34.53 - Posting.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Posting. 34.53 Section 34.53 Energy NUCLEAR REGULATORY COMMISSION LICENSES FOR INDUSTRIAL RADIOGRAPHY AND RADIATION SAFETY REQUIREMENTS FOR INDUSTRIAL RADIOGRAPHIC OPERATIONS Radiation Safety Requirements § 34.53 Posting. All areas in which industrial radiography is...

  15. Post Training Needs of Urban School Counselors.

    ERIC Educational Resources Information Center

    Henderson, Phyllis

    The post-training needs of school counselors employed in urban settings were investigated in this study. A questionnaire was completed by a total of 275 school counselors from 9 urban school districts in Ohio. The top four post-training needs reported by the school counselors were the desire for training in counseling students who: (1)…

  16. 77 FR 58592 - Modified Norway Post Agreement

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-21

    ... Modified Norway Post Agreement AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recently-filed Postal Service request to include a modified Norway Post Agreement... existing bilateral agreement for inbound competitive services with Posten Norge AS (Modified Norway...

  17. Post-Colonialism Perspectives on Educational Competition

    ERIC Educational Resources Information Center

    Yeh, Chuan-Rong

    2016-01-01

    Educational competition has always been the puzzle issue of educational researches. In this article, I analyze several aspects of educational competition within the perspective of post-colonialism discourse. In the political aspect, Taiwanese education is linked with political power, to present the post-colonial spirit by continuing dynastic…

  18. Post-emergence herbicides useful in calendula

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Easy and effective weed control is required by growers who are considering new industrial crops. Post-emergence herbicides typically are the products of choice by today’s growers. Unfortunately, post-emergence herbicides with proven safety margins are not known for calendula (Calendula officinalis),...

  19. 76 FR 65545 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-21

    ... informs the public that an appeal of the closing of the Agate, Colorado post office has been filed. It... received a petition for review of the Postal Service's determination to close the Agate post office in Agate, Colorado. The petition for review was filed online on October 12, 2011 by Gail Pitzer...

  20. 46 CFR Sec. 4 - Posting of bond.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 8 2011-10-01 2011-10-01 false Posting of bond. Sec. 4 Section 4 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION A-NATIONAL SHIPPING AUTHORITY BONDING OF SHIP'S PERSONNEL Sec. 4 Posting of bond. The General Agent shall retain an executed copy of each such bond in its principal...

  1. 46 CFR Sec. 4 - Posting of bond.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false Posting of bond. Sec. 4 Section 4 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION A-NATIONAL SHIPPING AUTHORITY BONDING OF SHIP'S PERSONNEL Sec. 4 Posting of bond. The General Agent shall retain an executed copy of each such bond in its principal...

  2. Vaccination in a post earthquake crisis.

    PubMed

    Wiwanitkit, Viroj

    2010-07-01

    Earthquakes are a kind of natural disaster. Several infectious diseases should be considered important emerging diseases in post-disaster situations and adequate prevention measures should be implemented in these circumstances. For prevention, vaccination is an important infection control method. In this brief article, the author will discuss the importance of vaccination in a post-earthquake situation.

  3. Post-Lie Algebras and Isospectral Flows

    NASA Astrophysics Data System (ADS)

    Ebrahimi-Fard, Kurusch; Lundervold, Alexander; Mencattini, Igor; Munthe-Kaas, Hans Z.

    2015-11-01

    In this paper we explore the Lie enveloping algebra of a post-Lie algebra derived from a classical R-matrix. An explicit exponential solution of the corresponding Lie bracket flow is presented. It is based on the solution of a post-Lie Magnus-type differential equation.

  4. 77 FR 3807 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-25

    ... informs the public that an appeal of the closing of the Badger, Iowa post office has been filed. It... Commission received four petitions for review of the Postal Service's determination to close the Badger post office in Badger, Iowa. The first petition for review received December 30, 2011, was filed by Myron...

  5. 46 CFR 169.217 - Posting.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Posting. 169.217 Section 169.217 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS SAILING SCHOOL VESSELS Inspection and Certification Certificate of Inspection § 169.217 Posting. The certificate of inspection must be framed...

  6. 77 FR 7213 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-10

    ... informs the public that an appeal of the closing of the Santa Fe, Missouri post office has been filed. It... Commission received two petitions for review of the Postal Service's determination to close the Santa Fe post office in Santa Fe, Missouri. The first petition for review received January 18, 2012, was filed...

  7. 76 FR 64127 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-17

    ... informs the public that an appeal of the closing of the Basalt, Idaho post office has been filed. It... received two petitions for review of the Postal Service's determination to close the Basalt post office in Basalt, Idaho. The petitions for review were filed by Franklyn and Nancy Freeman, and Paul and...

  8. 48 CFR 752.7029 - Post privileges.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Section 752.7029 Federal Acquisition Regulations System AGENCY FOR INTERNATIONAL DEVELOPMENT CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Texts of USAID Contract Clauses 752.7029 Post privileges. For use in all USAID non-commercial contracts involving performance overseas. Post...

  9. 46 CFR 196.12-1 - Posting.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Posting. 196.12-1 Section 196.12-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Stability Letter § 196.12-1 Posting. If a stability letter is issued in accordance with the requirements in § 170.120...

  10. 46 CFR 189.01-5 - Posting.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Posting. 189.01-5 Section 189.01-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS INSPECTION AND CERTIFICATION Certificate of Inspection § 189.01-5 Posting. (a) The original certificate of inspection shall, in general,...

  11. 46 CFR 189.01-5 - Posting.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Posting. 189.01-5 Section 189.01-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS INSPECTION AND CERTIFICATION Certificate of Inspection § 189.01-5 Posting. (a) The original certificate of inspection shall, in general,...

  12. 10 CFR 76.70 - Post issuance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 2 2014-01-01 2014-01-01 false Post issuance. 76.70 Section 76.70 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) CERTIFICATION OF GASEOUS DIFFUSION PLANTS Certification § 76.70 Post issuance. (a) Amendment of certificate terms and conditions. The terms and conditions of a certificate...

  13. 10 CFR 76.70 - Post issuance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 2 2013-01-01 2013-01-01 false Post issuance. 76.70 Section 76.70 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) CERTIFICATION OF GASEOUS DIFFUSION PLANTS Certification § 76.70 Post issuance. (a) Amendment of certificate terms and conditions. The terms and conditions of a certificate...

  14. 10 CFR 76.70 - Post issuance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 2 2011-01-01 2011-01-01 false Post issuance. 76.70 Section 76.70 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) CERTIFICATION OF GASEOUS DIFFUSION PLANTS Certification § 76.70 Post issuance. (a) Amendment of certificate terms and conditions. The terms and conditions of a certificate...

  15. 10 CFR 76.70 - Post issuance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Post issuance. 76.70 Section 76.70 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) CERTIFICATION OF GASEOUS DIFFUSION PLANTS Certification § 76.70 Post issuance. (a) Amendment of certificate terms and conditions. The terms and conditions of a certificate...

  16. 10 CFR 76.70 - Post issuance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 2 2012-01-01 2012-01-01 false Post issuance. 76.70 Section 76.70 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) CERTIFICATION OF GASEOUS DIFFUSION PLANTS Certification § 76.70 Post issuance. (a) Amendment of certificate terms and conditions. The terms and conditions of a certificate...

  17. 76 FR 76447 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-07

    ... informs the public that an appeal of the closing of the Miller, Nebraska post office has been filed. It... received a petition for review of the Postal Service's determination to close the Miller post office in Miller, Nebraska. The petition for review was filed by Teresa Saathoff, (Petitioner) and is...

  18. 75 FR 74109 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-30

    ... informs the public that an appeal of the closing of the Graves Mill, Virginia post office has been filed... for review of the closing of the Graves Mill Post Office located in Graves Mill, Virginia. The petition, which was filed by Douglas M. Graves (Petitioner), is postmarked November 15, 2010, and...

  19. 76 FR 72727 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-25

    ... informs the public that an appeal of the closing of the Lafayette, Kentucky post office has been filed. It... received a petition for review of the Postal Service's determination to close the Lafayette post office in Lafayette, Kentucky. The petition for review was filed by Ellin Francis, Mayor of Lafayette (Petitioner)...

  20. 77 FR 1962 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-12

    ... informs the public that an appeal of the closing of the Daisy, Georgia post office has been filed. It... Commission received eleven petitions for review of the Postal Service's determination to close the Daisy post office in Daisy, Georgia. The first petition for review received December 27, 2011, was filed by...

  1. Constructing Relationships in Post-Divorce Therapy.

    ERIC Educational Resources Information Center

    Chenail, Ronald J.; And Others

    This paper introduces a post-divorce therapy project in which therapists focus on communication patterns and help families resolve their problematic post-divorce situations by co-creating more useful ways of dealing with their disputes and conflicts. The paper also examines how therapists attempt to construct alternative relationships with and…

  2. 76 FR 58545 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-21

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Woodgate, New York post office has been filed....

  3. 76 FR 67768 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-02

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Sattley/Calpine, California post office has...

  4. 76 FR 70174 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-10

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Amoret, Missouri post office has been filed....

  5. 76 FR 46857 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-03

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Still Pond, Maryland post office has been...

  6. 76 FR 58544 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-21

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Latham, Missouri post office has been filed....

  7. 76 FR 77273 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-12

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Burns, Colorado post office has been filed....

  8. 76 FR 75916 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-05

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Prince, West Virginia post office has been...

  9. 76 FR 64132 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-17

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Saint Lucas, Iowa post office has been filed....

  10. 76 FR 76202 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-06

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Little America, Wyoming post office has been...

  11. 77 FR 4381 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-27

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Peterson, Minnesota post office has been filed....

  12. 76 FR 67773 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-02

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Ozan, Arkansas post office has been filed....

  13. 76 FR 28104 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-13

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Tateville, Kentucky post office has been filed....

  14. 76 FR 70173 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-10

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the West Edmeston, New York post office has been...

  15. 76 FR 61405 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-04

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Pomfret Center, Connecticut post office has...

  16. 76 FR 64129 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-17

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Balm, Florida post office has been filed....

  17. 76 FR 75917 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-05

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Fort Meade, South Dakota post office has...

  18. 76 FR 70175 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-10

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the New Boston, Illinois post office has been...

  19. 76 FR 67772 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-02

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Lodi, Texas post office has been filed....

  20. 76 FR 72985 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-28

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Witten, South Dakota post office has been...

  1. 76 FR 67002 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-28

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the New Hampton, Missouri post office has been...

  2. 76 FR 55951 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-09

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Bentonville, Ohio post office has been filed....

  3. 76 FR 73744 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-29

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Port Kent, New York post office has been filed....

  4. 76 FR 75569 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-02

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Prescott, Iowa post office has been filed....

  5. 76 FR 73746 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-29

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Rippey, Iowa post office has been filed....

  6. 76 FR 62097 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-06

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the West Stockholm, New York post office has...

  7. 77 FR 1754 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-11

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the St. Anthony, Iowa post office has been filed....

  8. 76 FR 73745 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-29

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Deering, Missouri post office has been filed....

  9. 77 FR 4377 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-27

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Randolph, Iowa post office has been filed....

  10. 76 FR 64131 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-17

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Bloomington, Idaho post office has been filed....

  11. 77 FR 3809 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-25

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Pierceville, Indiana post office has been...

  12. 76 FR 61403 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-04

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Redfield, New York post office has been filed....

  13. 76 FR 67767 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-02

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Glenwood, Alabama post office has been filed....

  14. 76 FR 61758 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-05

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Argyle, Florida post office has been filed....

  15. 77 FR 4383 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-27

    ... From the Federal Register Online via the Government Publishing Office ] POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Elwell, Michigan post office has been filed....

  16. 76 FR 75918 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-05

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Lanagan, Missouri post office has been filed....

  17. 76 FR 67766 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-02

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Saratoga, Arkansas post office has been filed....

  18. 76 FR 67770 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-02

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Fairfield, Kentucky post office has been filed....

  19. 76 FR 55952 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-09

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Velpen, Indiana post office has been filed....

  20. 76 FR 28103 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-13

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Gywnedd, Pennsylvania post office has been...

  1. 76 FR 44054 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-22

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Ukiah, California Main Post Office has been...

  2. 77 FR 3808 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-25

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Chilo, Ohio post office has been filed....

  3. 77 FR 1755 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-11

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Halsey, Nebraska post office has been filed....

  4. 76 FR 64130 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-17

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Scott, Mississippi post office has been filed....

  5. 76 FR 71083 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-16

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Andover, Illinois post office has been filed....

  6. 76 FR 78320 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-16

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the South Greenfield, Missouri post office has...

  7. 76 FR 71084 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-16

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Orchard, Iowa post office has been filed....

  8. 76 FR 78319 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-16

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Phippsburg, Colorado post office has been...

  9. 76 FR 78318 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-16

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Harris, Iowa post office has been filed....

  10. 76 FR 73742 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-29

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the consolidation of the Slayden, Tennessee post office has...

  11. 76 FR 67000 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-28

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Jenkinjones, West Virginia post office has...

  12. 75 FR 66804 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-29

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This notice advises... issues raised include: Failure to follow the post office closure requirements. See 39 U.S.C....

  13. 76 FR 67001 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-28

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Witter, Arkansas post office has been filed....

  14. 76 FR 64133 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-17

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Campaign, Tennessee post office has been filed....

  15. 75 FR 78778 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-16

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Holmes Mill (Kentucky) Post Office has been...

  16. 77 FR 1752 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-11

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Ashton, Iowa, post office has been filed....

  17. 77 FR 1751 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-11

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Strandquist, Minnesota post office has been...

  18. 76 FR 75568 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-02

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the New Cambria, Kansas post office has been filed....

  19. 77 FR 3805 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-25

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Bovill, Idaho post office has been filed....

  20. 77 FR 4380 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-27

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Ponce de Leon, Missouri post office has been...

  1. 76 FR 73743 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-29

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Nemaha, Nebraska post office has been filed....

  2. 76 FR 82003 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-29

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Fostoria, Iowa post office has been filed....

  3. 77 FR 4379 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-27

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Highfalls, North Carolina post office has...

  4. 76 FR 67003 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-28

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Adona, Arkansas post office has been filed....

  5. 76 FR 58546 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-21

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Hailesboro, New York post office has been...

  6. 76 FR 67771 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-02

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the St. Olaf, Iowa post office has been filed....

  7. 76 FR 64134 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-17

    ... informs the public that an appeal of the closing of the Conception Junction, Missouri post office has been... Junction post office in Conception Junction, Missouri. The petition for review was filed by Richard L... Federal government holidays. Docket section personnel may be contacted via electronic mail at...

  8. 46 CFR 196.12-1 - Posting.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Posting. 196.12-1 Section 196.12-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Stability Letter § 196.12-1 Posting. If a stability letter is issued in accordance with the requirements in § 170.120...

  9. Academic Community and Post-Tenure Review.

    ERIC Educational Resources Information Center

    Tierney, William G.

    1997-01-01

    Discusses the need for post-tenure faculty review to root out "dead wood" faculty and increase faculty accountability, focusing on the time frame for such reviews, who gets reviewed, and the intensity and ramifications of the review. Also notes criticisms of post-tenure reviews and the need to build community through self-regulation.…

  10. 76 FR 62461 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-07

    ... informs the public that an appeal of the closing of the Oak Hill, Alabama post office has been filed. It... Postal Service's determination to close the Oak Hill post office in Oak Hill, Alabama. The petition for review was filed by the Patrons of Oak Hill (Petitioner) and is postmarked September 19, 2011....

  11. 77 FR 1750 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-11

    ... informs the public that an appeal of the closing of the Elk River, Idaho post office has been filed. It... Commission received a petition for review of the Postal Service's determination to close the Elk River post office in Elk River, Idaho. The petition for review received December 20, 2011, was filed by Dawn...

  12. 76 FR 71085 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-16

    ... informs the public that an appeal of the closing of the Deer Grove, Illinois post office has been filed... received a petition for review of the Postal Service's determination to close the Deer Grove post office in Deer Grove, Illinois. The petition for review was filed by Galen R. Hooper (Petitioner) and...

  13. 76 FR 69297 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-08

    ... informs the public that an appeal of the closing of the East Poland, Maine post office has been filed. It... received two petitions for review of the Postal Service's determination to close the East Poland post office in East Poland, Maine. The first petition for review was filed by Carl E. Duchette. The...

  14. 10 CFR 1048.6 - Posting.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Posting. 1048.6 Section 1048.6 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) TRESPASSING ON STRATEGIC PETROLEUM RESERVE FACILITIES AND OTHER PROPERTY § 1048.6 Posting. Notices stating the pertinent prohibitions of §§ 1048.3 and 1048.4 and the penalties of §...

  15. 10 CFR 1048.6 - Posting.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Posting. 1048.6 Section 1048.6 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) TRESPASSING ON STRATEGIC PETROLEUM RESERVE FACILITIES AND OTHER PROPERTY § 1048.6 Posting. Notices stating the pertinent prohibitions of §§ 1048.3 and 1048.4 and the penalties of §...

  16. 42 CFR 124.604 - Posted notice.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... room. (b) If in the service area of the facility the “usual language of households” of ten percent or... other than English or Spanish, the facility shall translate the notice into that language and post the translated notice on signs substantially similar in size and legibility to, and posted with, those...

  17. Post-Retrofit Residential Assessments

    SciTech Connect

    Lancaster, Ross; lutzenhiser, Loren; Moezzi, Mithra; Widder, Sarah H.; Chandra, Subrato; Baechler, Michael C.

    2012-04-30

    This study examined a range of factors influencing energy consumption in households that had participated in residential energy-efficiency upgrades. The study was funded by a grant from the U.S. Department of Energy’s Pacific Northwest National Laboratory and was conducted by faculty and staff of Portland State University Center for Urban Studies and Department of Economics. This work was made possible through the assistance and support of the Energy Trust of Oregon (ETO), whose residential energy-efficiency programs provided the population from which the sample cases were drawn. All households in the study had participated in the ETO Home Performance with Energy Star (HPwES) program. A number of these had concurrently pursued measures through other ETO programs. Post-retrofit energy outcomes are rarely investigated on a house-by-house basis. Rather, aggregate changes are ordinarily the focus of program impact evaluations, with deviation from aggregate expectations chalked up to measurement error, the vagaries of weather and idiosyncrasies of occupants. However, understanding how homes perform post-retrofit on an individual basis can give important insights to increase energy savings at the participant and the programmatic level. Taking a more disaggregated approach, this study analyzed energy consumption data from before and after the retrofit activity and made comparisons with engineering estimates for the upgrades, to identify households that performed differently from what may have been expected based on the estimates. A statistical analysis using hierarchal linear models, which accounted for weather variations, was performed looking separately at gas and electrical use during the periods before and after upgrades took place. A more straightforward comparison of billing data for 12-month periods before and after the intervention was also performed, yielding the majority of the cases examined. The later approach allowed total energy use and costs to be

  18. Explosive signatures: Pre & post blast

    NASA Astrophysics Data System (ADS)

    Bernier, Evan Thomas

    Manuscripts 1 and 2 of this dissertation both involve the pre-blast detection of trace explosive material. The first manuscript explores the analysis of human hair as an indicator of exposure to explosives. Field analysis of hair for trace explosives is quick and non-invasive, and could prove to be a powerful linkage to physical evidence in the form of bulk explosive material. Individuals tested were involved in studies which required handling or close proximity to bulk high explosives such as TNT, PETN, and RDX. The second manuscript reports the results of research in the design and application of canine training aids for non-traditional, peroxide-based explosives. Organic peroxides such as triacetonetriperoxide (TATP) and hexamethylenetriperoxidediamine (HMTD) can be synthesized relatively easily with store-bought ingredients and have become popular improvised explosives with many terrorist groups. Due to the hazards of handling such sensitive compounds, this research established methods for preparing training aids which contained safe quantities of TATP and HMTD for use in imprinting canines with their characteristic odor. Manuscripts 3 and 4 of this dissertation focus on research conducted to characterize pipe bombs during and after an explosion (post-blast). Pipe bombs represent a large percentage of domestic devices encountered by law enforcement. The current project has involved the preparation and controlled explosion of over 90 pipe bombs of different configurations in order to obtain data on fragmentation patterns, fragment velocity, blast overpressure, and fragmentation distance. Physical data recorded from the collected fragments, such as mass, size, and thickness, was correlated with the relative power of the initial device. Manuscript 4 explores the microstructural analysis of select pipe bomb fragments. Shock-loading of the pipe steel led to plastic deformation and work hardening in the steel grain structure as evidenced by optical microscopy and

  19. Image post-processing in dental practice.

    PubMed

    Gormez, Ozlem; Yilmaz, Hasan Huseyin

    2009-10-01

    Image post-processing of dental digital radiographs, a function which used commonly in dental practice is presented in this article. Digital radiography has been available in dentistry for more than 25 years and its use by dental practitioners is steadily increasing. Digital acquisition of radiographs enables computer-based image post-processing to enhance image quality and increase the accuracy of interpretation. Image post-processing applications can easily be practiced in dental office by a computer and image processing programs. In this article, image post-processing operations such as image restoration, image enhancement, image analysis, image synthesis, and image compression, and their diagnostic efficacy is described. In addition this article provides general dental practitioners with a broad overview of the benefits of the different image post-processing operations to help them understand the role of that the technology can play in their practices.

  20. Fiber post techniques for anatomical root variations.

    PubMed

    Boksman, Leendert; Hepburn, Alejandro Bertoldi; Kogan, Enrique; Friedman, Manny; de Rijk, Waldemar

    2011-05-01

    In contemporary dental practice, there is no remaining reason to use metallic posts, custom or prefabricated. Many cases that several years ago would have required a retentive post will not require that post today, because of the many improvements in bonding agents and composite resin restoratives. However, in cases where less than 50% of coronal tooth structure remains--or in other cases wherein the judgment of the clinician a post is indicated--there are now aesthetic, non-corrosive, fracture resistant and radiopaque alternatives for all varieties that save time and money without compromise. Their most compelling advantage, regardless of the geometry or amount of residual tooth structure, is the protection from root fracture that a low modulus restoration provides. In selecting the materials (posts, resins) for these techniques, the dentist is advised not to cut corners, and to seek the strongest and most radiopaque products available.

  1. Recovery from post-operative anaemia.

    PubMed

    Wallis, J P; Wells, A W; Whitehead, S; Brewster, N

    2005-10-01

    Acceptance of lower transfusion thresholds and shorter post-operative stays results in patients leaving hospital after surgery with lower haemoglobin (Hb) than previously. We undertook a prospective observational study to assess the haematological response to post-operative anaemia and to determine the utility of quality of life (QoL) measures in assessing the impact of anaemia on such patients. Thirty patients undergoing unilateral hip arthroplasty had blood samples taken and QoL questionnaires administered pre-operatively and at 7, 28 and 56 days post-operatively. Increased erythropoiesis was evident at day 7 post-operatively. Approximately two-thirds of the post-operative Hb deficit was corrected by day 28. There was evidence of functional iron deficiency in more than one-quarter of patients at day 56. QoL scores used did not show any relationship with Hb in the post-operative period. Red cell 2,3-diphosphoglycerate (2,3DPG) levels increased in proportion to the degree of post-operative anaemia. We concluded that substantial recovery of Hb occurs between day 7 and day 28 post-operatively. Complete recovery of Hb may be delayed beyond day 56 due to development of iron deficiency. Patients are at significant risk of developing post-operative iron deficiency depending on operative blood loss and pre-operative iron stores. Increased red cell 2,3DPG may offset the effect of anaemia on oxygen delivery. We found no evidence that anaemia produces a measurable effect on chosen QoL scores in the post-operative period.

  2. Quick response airborne command post communications

    NASA Astrophysics Data System (ADS)

    Blaisdell, Randy L.

    1988-08-01

    National emergencies and strategic crises come in all forms and sizes ranging from natural disasters at one end of the scale up to and including global nuclear warfare at the other. Since the early 1960s the U.S. Government has spent billions of dollars fielding airborne command posts to ensure continuity of government and the command and control function during times of theater conventional, theater nuclear, and global nuclear warfare. Unfortunately, cost has prevented the extension of the airborne command post technology developed for these relatively unlikely events to the lower level, though much more likely to occur, crises such as natural disasters, terrorist acts, political insurgencies, etc. This thesis proposes the implementation of an economical airborne command post concept to address the wide variety of crises ignored by existing military airborne command posts. The system is known as the Quick Response Airborne Command Post (QRAC Post) and is based on the exclusive use of commercially owned and operated aircraft, and commercially available automated data processing and communications resources. The thesis addresses the QRAC Post concept at a systems level and is primarily intended to demonstrate how current technology can be exploited to economically achieve a national objective.

  3. Development of new radiopaque glass fiber posts.

    PubMed

    Furtos, Gabriel; Baldea, Bogdan; Silaghi-Dumitrescu, Laura

    2016-02-01

    The aim of this study was to analyze the radiopacity and filler content of three experimental glass fiber posts (EGFP) in comparison with other glass/carbon fibers and metal posts from the dental market. Three EGFP were obtained by pultrusion of glass fibers in a polymer matrix based on 2,2-bis[4-(2-hydroxy-3-methacryloyloxypropoxy)-phenyl]propane (bis-GMA) and triethyleneglycol dimethacrylate (TEGDMA) monomers. Using intraoral sensor disks 27 posts, as well as mesiodistal sections of human molar and aluminum step wedges were radiographed for evaluation of radiopacity. The percentage compositions of fillers by weight and volume were investigated by combustion analysis. Two EGFP showed radiopacity higher than enamel. The commercial endodontic posts showed radiopacity as follows: higher than enamel, between enamel and dentin, and lower than dentin. The results showed statistically significant differences (p b 0.05)when evaluatedwith one-way ANOVA statistical analysis. According to combustion analyses, the filler content of the tested posts ranges between 58.84wt.% and 86.02wt.%. The filler content of the tested EGFP ranged between 68.91 wt.% and 79.04 wt.%. EGFP could be an alternative to commercial glass fiber posts. Futureglass fiber posts are recommended to present higher radiopacity than dentin and perhaps ideally similar to or higher than that of enamel, for improved clinical detection. The posts with a lower radiopacity than dentin should be considered insufficiently radiopaque. The radiopacity of some glass fiber posts is not greatly influenced by the amount of filler.

  4. Post-caesarean analgesia: What is new?

    PubMed Central

    Kerai, Sukhyanti; Saxena, Kirti Nath; Taneja, Bharti

    2017-01-01

    Adequate post-operative analgesia after caesarean section (CS) is vital as it impacts the distinct surgical recovery requirements of the parturient. Although newer analgesic modalities and drugs for post-caesarean analgesia have been introduced over the recent years, review of the literature suggests suggests that we are far from achieving the goals of optimum post-operative analgesia. We conducted a systematic review of recent advances in modalities for post-caesarean analgesia. After systematic search and quality assessment of studies, we included a total of 51 randomised controlled trials that evaluated the role of opioids, transversus abdominis plane (TAP) block, wound infiltration/infusion, ketamine, gabapentin and ilioinguinal-iliohypogastric nerve block (II-IH NB) for post-caesarean analgesia. Administration of opioids still remains the gold standard for post-operative analgesia, but the associated troublesome side effects have led to the mandatory incorporation of non-opioid analgesics in post-CS analgesia regime. Among the non-opioid techniques, TAP block is the most investigated modality of the last decade. The analgesic efficacy of TAP block as a part of multimodal analgesia is established in post-CS cases where intrathecal morphine is not employed and in CS under general anaesthesia. Among non-steroidal anti-inflammatory drugs, COX-I inhibitors and intravenous paracetamol are found to be useful in post-operative analgesic regimen. The perioperative use of ketamine is found useful only in CS done under spinal anaesthesia; no benefit is seen where general anaesthesia is employed. Wound infiltration with local anaesthetics, systemic gabapentin and II-IH NB need further trials to assess their efficacy.

  5. Esthetic post-and-core treatment.

    PubMed

    Freedman, G A

    2001-01-01

    The dilemma that confronts the practitioner in the area of post-endodontic rehabilitation is a positive one. The variety of products and techniques available offer practical solutions to most restorative problems. Patients have benefited [figure: see text] from recent developments in post-and-core technology, and continue to reap the benefits of research and development. The ideal system of products for the endodontic-restorative continuum includes: an esthetic resin fiber post a composite core an automixed resin luting cement current techniques that combine the automixed resin luting cement and composite core into the same component.

  6. Post-stroke language disorders.

    PubMed

    Sinanović, Osman; Mrkonjić, Zamir; Zukić, Sanela; Vidović, Mirjana; Imamović, Kata

    2011-03-01

    Post-stroke language disorders are frequent and include aphasia, alexia, agraphia and acalculia. There are different definitions of aphasias, but the most widely accepted neurologic and/or neuropsychological definition is that aphasia is a loss or impairment of verbal communication, which occurs as a consequence of brain dysfunction. It manifests as impairment of almost all verbal abilities, e.g., abnormal verbal expression, difficulties in understanding spoken or written language, repetition, naming, reading and writing. During the history, many classifications of aphasia syndromes were established. For practical use, classification of aphasias according to fluency, comprehension and abilities of naming it seems to be most suitable (nonfluent aphasias: Broca's, transcortical motor, global and mixed transcortical aphasia; fluent aphasias: anomic, conduction, Wernicke's, transcortical sensory, subcortical aphasia). Aphasia is a common consequence of left hemispheric lesion and most common neuropsychological consequence of stroke, with a prevalence of one-third of all stroke patients in acute phase, although there are reports on even higher figures. Many speech impairments have a tendency of spontaneous recovery. Spontaneous recovery is most remarkable in the first three months after stroke onset. Recovery of aphasias caused by ischemic stroke occurs earlier and it is most intensive in the first two weeks. In aphasias caused by hemorrhagic stroke, spontaneous recovery is slower and occurs from the fourth to the eighth week after stroke. The course and outcome of aphasia depend greatly on the type of aphasia. Regardless of the fact that a significant number of aphasias spontaneously improve, it is necessary to start treatment as soon as possible. The writing and reading disorders in stroke patients (alexias and agraphias) are more frequent than verified on routine examination, not only in less developed but also in large neurologic departments. Alexia is an acquired

  7. 49 CFR 663.39 - Post-delivery audit review.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 7 2010-10-01 2010-10-01 false Post-delivery audit review. 663.39 Section 663.39..., DEPARTMENT OF TRANSPORTATION PRE-AWARD AND POST-DELIVERY AUDITS OF ROLLING STOCK PURCHASES Post-Delivery Audits § 663.39 Post-delivery audit review. (a) If a recipient cannot complete a post-delivery...

  8. 49 CFR 663.39 - Post-delivery audit review.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 7 2011-10-01 2011-10-01 false Post-delivery audit review. 663.39 Section 663.39..., DEPARTMENT OF TRANSPORTATION PRE-AWARD AND POST-DELIVERY AUDITS OF ROLLING STOCK PURCHASES Post-Delivery Audits § 663.39 Post-delivery audit review. (a) If a recipient cannot complete a post-delivery...

  9. Apollo 13 Facts [Post Flight Press Conference

    NASA Technical Reports Server (NTRS)

    2001-01-01

    The Apollo 13 astronauts, James Lovell, Jr., John Swigert, Jr., and Fred Haise, Jr., are seen during this post flight press conference. They describe their mission and answer questions from the audience.

  10. Post Office Modernization Act of 2009

    THOMAS, 111th Congress

    Rep. Stupak, Bart [D-MI-1

    2009-04-02

    07/31/2009 Referred to the Subcommittee on Federal Workforce, Post Office, and the District of Columbia. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  11. Post-communism: postmodernity or modernity revisited?

    PubMed

    Ray, L

    1997-12-01

    Coinciding with the popularity of postmodern theory, the fall of communism appeared to offer further evidence of the exhaustion of modernity. Such analysis is grounded in a view that the Soviet system was the epitome of modernity. An alternative approach regards post-communism as opening new terrains of struggle for modernity. Thus Habermas and others suggest that post-communist societies are rejoining the trajectory of western modernity whose problems they now recapitulate. This alternative view implies that Soviet systems were something other than 'modern', although their nature is not always clearly defined. However, even if post-communist societies do encounter problems of modernity, they do so in new circumstances where modernist notions of social development have become problematic. This article argues that, contrary to those who regard modernization or postmodernization as irresistible trends, core post-communist societies are likely to develop along an alternative path to that of western modernity. This is tentatively described as 'neo-mercantilist'.

  12. Post-operative pulmonary complications after thoracotomy

    PubMed Central

    Sengupta, Saikat

    2015-01-01

    Pulmonary complications are a major cause of morbidity and mortality in the post-operative period after thoracotomy. The type of complications and the severity of complications depend on the type of thoracic surgery that has been performed as well as on the patient's pre-operative medical status. Risk stratification can help in predicting the possibility of the post-operative complications. Certain airway complications are more prone to develop with thoracic surgery. Vocal cord injuries, bronchopleural fistulae, pulmonary emboli and post-thoracic surgery non-cardiogenic pulmonary oedema are some of the unique complications that occur in this subset of patients. The major pulmonary complications such as atelectasis, bronchospasm and pneumonia can lead to respiratory failure. This review was compiled after a search for search terms within ‘post-operative pulmonary complications after thoracic surgery and thoracotomy’ on search engines including PubMed and standard text references on the subject from 2000 to 2015. PMID:26556921

  13. Post-Menopausal? Give Exercise a Try

    MedlinePlus

    ... gov/news/fullstory_163625.html Post-Menopausal? Give Exercise a Try Study participants were fitter, felt better -- ... Feb. 16, 2017 (HealthDay News) -- After menopause, moderate exercise can help women manage hot flashes, become more ...

  14. Post-quantum key exchange protocols

    NASA Astrophysics Data System (ADS)

    Li, Xiangdong; Leung, Lin; Kwan, Andis Chi-Tung; Zhang, Xiaowen; Kahanda, Dammika; Anshel, Michael

    2006-05-01

    If an eavesdropper Eve is equipped with quantum computers, she can easily break the public key exchange protocols used today. In this paper we will discuss the post-quantum Diffie-Hellman key exchange and private key exchange protocols.

  15. POST - A New Look at Stratocumulus

    DTIC Science & Technology

    2010-07-01

    1 10.1 POST - A New Look at Stratocumulus H. Gerber , G. Frick , S. P. Malinowski , W . Kumula , S...interesting to note that another flight shows entirely different behavior: Malinowski et al (2010) finds positive T’ in LW C holes near cloud top in...parameterization will also rely on ongoing analysis by POST colleagues described in Malinowski et al (2010), Hill et al (2010), W ang, Q., et al (2010), and W ang

  16. Cloverleaf Vibratory Microgyroscope with Integrated Post

    NASA Technical Reports Server (NTRS)

    Tang, Tony K.; Gutierrez, Roman; Roger, Damien

    2003-01-01

    A modified design and fabrication sequence has been devised to improve the performance of a cloverleaf vibratory microgyroscope that includes an axial rod or post rigidly attached to the center of the cloverleaf structure. The basic concepts of cloverleaf vibratory microgyroscopes, without and with rods or posts, were described in two prior articles in NASA Tech Briefs, Vol. 21, No. 9 (September 1997): Micromachined Planar Vibratory Microgyroscopes (NPO-19713), page 68 and Planar Vibratory Microgyroscope: Alternative Configuration (NPO-19714), page 70. As described in more detail in the second-mentioned prior article, the cloverleaf-shaped structure and the rod or post are parts of a vibratory element that senses rotation via the effect of the Coriolis force upon its vibrations. Heretofore, the posts for devices of this type have been fabricated separately, then assembled manually onto the cloverleaf structures. The resulting imperfections in the assembled units have given rise to asymmetric stresses in the cloverleaf structures and, consequently, to changes in resonant frequencies of vibration and in shapes of vibration modes. These changes, in turn, have caused variations in performance among nominally identical devices. The modified design provides for the fabrication of the upper half of the post as an integral part of the cloverleaf structure; this is accomplished by reactive-ion etching of a single-piece half-post-and-cloverleaf structure from a wafer of silicon. The lower half of the post and a baseplate are also a single piece made by reactive-ion etching from a wafer of silicon. The two pieces are bonded together (see figure) by a thermal-compression metal-to-metal bonding technique to form a cloverleaf gyroscope with an integrated post structure..

  17. NASA thesaurus combined file postings statistics

    NASA Technical Reports Server (NTRS)

    1993-01-01

    The NASA Thesaurus Combined File Postings Statistics is published semiannually (January and July). This alphabetical listing of postable subject terms contained in the NASA Thesaurus is used to display the number of postings (documents) indexed by each subject term from 1968 to date. The postings totals per item are separated by announcement of other media into STAR, IAA, COSMIC, and OTHER, columnar entries covering the NASA document collection (1968 to date). This is a cumulative publication, and except for special cases, no reference is needed to previous issuances. Retention of the January 1992 issue could be helpful for book information. With the July 1992 issue, NALNET book statistics have been replaced by COSMIC statistics for NASA funded software. File postings statistics for the Alternate Data Base covering NASA collection from 1962 through 1967 were published on a one-time basis in September 1975. Subject terms for the Alternate Data Base are derived from the subject Authority List, reprinted 1985, which is available upon request. The distribution of 19,697,748 postings among the 17,446 NASA Thesaurus terms is tabulated on the last page of the NASA Thesaurus Combined File Postings Statistics.

  18. Post-human body and beauty.

    PubMed

    Russo, Maria Teresa; Di Stefano, Nicola

    2014-01-01

    The article calls into question the very possibility of a post-human aesthetics, starting from the following premise: rather than post-human, it is more correct to speak of post-natural, indicating by this expression a reality produced through a new type of evolution, which does not simply change human nature, but de-natures it, radically transforming it into an artefact. This post-nature which aspires to be perfect, immortal, invulnerable, is entirely devoid of beauty. In fact, while there may be an aesthetic of the artificial and of the artefact if it is in relation to objects, there is, however, no aesthetic of the post-human body. This is because is configured as a non-body and does not have the characteristics for what is commonly intended as beauty (harmony between matter and form, a reflection of inner life, uniqueness). Also in this case, it is more correct to speak of post-beauty, which in its properties appears to be the mirror image of beauty and ultimately, represents its complete dissolution.

  19. Content analysis of cancer blog posts*

    PubMed Central

    Kim, Sujin

    2009-01-01

    Objectives: The efficacy of user-defined subject tagging and software-generated subject tagging for describing and organizing cancer blog contents was explored. Methods: The Technorati search engine was used to search the blogosphere for cancer blog postings generated during a two-month period. Postings were mined for relevant subject concepts, and blogger-defined tags and Text Analysis Portal for Research (TAPoR) software–defined tags were generated for each message. Descriptive data were collected, and the blogger-defined tags were compared with software-generated tags. Three standard vocabularies (Opinion Templates, Basic Resource, and Medical Subject Headings [MeSH] Resource) were used to assign subject terms to the blogs, with results compared for efficacy in information retrieval. Results: Descriptive data showed that most of the studied cancer blogs (80%) contained fewer than 500 words each. The numbers of blogger-defined tags per posting (M = 4.49 per posting) were significantly smaller than the TAPoR keywords (M = 23.55 per posting). Both blogger-defined subject tags and software-generated subject tags were often overly broad or overly narrow in focus, producing less than effective search results for those seeking to extract information from cancer blogs. Conclusions: Additional exploration into methods for systematically organizing cancer blog postings is necessary if blogs are to become stable and efficacious information resources for cancer patients, friends, families, or providers. PMID:19851489

  20. Microbiological Study of Cast Posts before Cementation

    PubMed Central

    Ojeda-Garces, Juan Carlos

    2017-01-01

    This study identifies the most common microorganisms present in type III gold cast posts related to pulpal disease and evaluates the sterilization/disinfection method before cementation in the root canal. Forty-five type III gold cast posts were aseptically collected in sterile sealed plastic bags and taken to the microbiology laboratory to carry out the study: fifteen cast posts had no treatment, fifteen were disinfected (immersion in 70% alcohol during 15 minutes), and fifteen were autoclaved at 121°C for 15 minutes by using saturated steam under 15 psi pressure. By using a two-proportion z-test, the difference was statistically significant (p > 0.05) and demonstrates that, in spite of the aseptic pattern used in the cast post collection and laboratory procedures, some cast posts arrive contaminated at the consulting office. The disinfection process worked out in a high percentage and demonstrated that the sterilization by autoclaving eliminated completely the pathogenic microbiota without affecting the cast post shape and integrity that could compromise their final fitting. PMID:28316625

  1. Post silanization improves bond strength of translucent posts to flowable composite resins.

    PubMed

    Albaladejo, Alberto; Osorio, Raquel; Papacchini, Federica; Goracci, Cecilia; Toledano, Manuel; Ferrari, Marco

    2007-08-01

    The aim of the study is to evaluate the effect of post silanization on the microtensile bond strength (MTBS) of translucent fiber posts to seven flowable composite resins used as core material. Seventy fiber posts were employed. In half of the posts, silanization was performed with Monobond-S. A cylindrical plastic matrix was placed around the post and filled with different resins: UniFil Flow Experimental, UniFil Low Flow Plus Experimental, Venus Flow, Revolution Formula 2, Point 4 Flowable, X-Flow, and Wave mv. Five posts were bonded per group. After polymerization, two longitudinal cuts were made on two opposite sides of the post at its outermost periphery. Then, each specimen was serially sectioned, obtaining 30-35 beams with 1-mm(2) cross-sectional area. Each beam was tested in tension in an Instron machine at 0.5 mm/min. ANOVA and Student Newman Keuls tests were performed. The different resin composite materials and the post silanization procedure had a significant effect on MTBS. The application of a silane coupling agent increased MTBS of flowable composite resins to translucent posts. X-flow and Point 4 attained the highest MTBS regardless of the silane treatment.

  2. Comparison of carbon fiber and stainless steel root canal posts.

    PubMed

    Purton, D G; Payne, J A

    1996-02-01

    This in vitro study compared physical properties of root canal posts made of carbon fiber-reinforced epoxy resin with those of stainless steel posts. Three-point bending tests were used to derive the transverse modulus of elasticity of the posts. Resin composite cores on the posts were subjected to tensile forces to test the bonds between the cores and posts. Carbon fiber posts appeared to have adequate rigidity for their designed purpose. The bond strength of the resin composite cores to the carbon fiber posts was significantly less than that to the stainless steel posts.

  3. Post-partum acute kidney injury.

    PubMed

    Pahwa, Naresh; Bharani, Rajesh; Kumar, Ravindra

    2014-11-01

    To determine the risk factors, course of hospital stay and mortality rate among women with post-partum acute kidney injury (AKI), we studied (of 752 patients with AKI admitted to a tertiary care center during the study period between November 2009 and August 2012) 27 (3.59%) women with post-partum AKI. The data regarding age, parity, cause of renal failure, course of hospital stay and requirement of dialysis were recorded. Sepsis was the major cause (70.3%) of post-partum AKI. Other causes included disseminated intravascular coagulation (55.5%), pre-eclampsia/eclampsia (40.7%), ante- and post-partum hemorrhage (40.7% and 22.2%) and hemolytic anemia and elevated liver enzymes and low platelet count syndrome (29.6%); most patients had more than one cause of AKI. We found a very high prevalence (18.5%) of cortical necrosis in our study patients. A significant correlation was also found between the creatinine level on admission and the period of onset of disease after delivery. In conclusion, several factors are involved in causing post-partum AKI in our population, and sepsis was the most common of them.

  4. [Hypertension and pregnancy: Post-partum period].

    PubMed

    Hugon-Rodin, Justine; Plu-Bureau, Geneviève

    2016-01-01

    Post-partum period is associated with specific characteristics in women with gestational disorders or preeclampsia. For breastfeeding women, the choice of antihypertensive treatment should take into account the impact on child health. The impact of breastfeeding on health mother must be also discussed. Moreover, for lactation inhibition, bromocriptine should not be used, especially in the context of gestational disorders. In post-partum period, the best contraceptive strategy is only-progestin contraception or non-hormonal contraceptives use. However, this choice will depend on the stabilization or normalization of blood pressure in early post-partum period. Finally, several consultations should be suggested: an information and announcement to explain the consequences of these gestational disorders and organize their multidisciplinary management and follow-up. A preconceptional consultation takes its place to anticipate potential recurrent preeclampsia or gestational hypertension and to schedule a future pregnancy in optimal conditions.

  5. Post-shock temperatures in minerals

    NASA Technical Reports Server (NTRS)

    Raikes, S. A.; Ahrens, T. J.

    1979-01-01

    An experimental technique for the measurement of post-shock temperatures in minerals is presented, and silicate post-shock temperature measurements are compared with theoretical calculations. The technique involves the use of infrared detectors to determine the brightness temperatures at 4.5 to 5.75 microns and 7 to 14 microns of samples shocked to between 5 and 30 GPa. Results obtained for aluminum 2024 and stainless steel 304, as well as for Bamble bronzite and synthetic crystal forsterite are found at low pressures to be considerably in excess of the temperatures predicted assuming a hydrodynamic rheology and isentropic release parallel to the Hugoniot. The results are shown to be in better agreement, however, with values calculated assuming elastoplastic behavior, and the post-shock temperatures of crystalline quartz are found to be in good agreement with those calculated by Mashimo et al. (1979) from release adiabat data.

  6. Sperm harvesting and post-mortem fatherhood.

    PubMed

    Murphy, Timothy F

    1995-10-01

    The motives and consequences of harvesting sperm from brain dead males for the purpose of effecting post mortem fatherhood are examined. I argue that sperm harvesting and post mortem fatherhood raise no harms of a magnitude that would justify forbidding the practice outright. Dead men are not obviously harmed by the practice; children need not be harmed by this kind of birth; and the practice enlarges rather than diminishes the reproductive choices of surviving partners. Certain ethical and legal issues nevertheless require attention. As a matter of consistency with other harvesting protocols, there ought to be a mechanism for respecting the wishes of men who when alive do not wish to become fathers post mortem. Mechanisms governing entitlement to harvest and use sperm will also be required. I note that the law is unlikely to recognize the paternity of children born from harvested sperm, though there may be reasons to recognize that paternity in some instances.

  7. [Herpes zoster and post-herpetic neuralgia].

    PubMed

    Hashizume, K

    2001-09-01

    Pain associated with herpes zoster arise from the virul neuritis of the suffered trigeminal or spinal dorsal ganglion. Prolonged neuritis makes an irreversible nerve injury and continuous pain impulse develops a central sensitization. A post-herpetic neuralgia is thought to be a neuropathic pain due to the irreversible nerve injury and sensitization. It is important to treat herpetic pain completely before the development of the post-herpetic neuralgia, because there are few effective therapies to cure post-herpetic neuralgia. A sympathetic nerve block increases the nerve blood flow supply, and may improve the nerve injury. It is also known that some sympathetic mechanisms relate to the development of the sensitization. A sensory nerve block reduces pain impulse to the dorsal horn, and may interfere the sensitization. A cortico-steroid administrated with a nerve block can reduce the neuritis, and may improve the nerve injury.

  8. New horizons in post-marketing surveillance.

    PubMed

    Waller, P; Wood, S

    1993-01-01

    Post-marketing surveillance is the process of monitoring and evaluating the safety of marketed medicines using a variety of methods. However, many doctors believe that post-marketing surveillance has a more limited meaning, ie an observational study of a new medicine sponsored by a pharmaceutical company. Although such studies were performed extensively in the United Kingdom during the 1980s, few have been published. Their purpose was to study large populations of users in ordinary practice with the aim of identifying hazards that had been missed, because clinical trials were too small, too short or did not always reflect real life. To some extent these studies have now fallen into disrepute, both on scientific grounds and because they have often been thought to be a thinly-disguised promotional exercise. The purpose of this article is to examine some of the previous problems with post-marketing surveillance and to propose new directions for the future.

  9. Adolf Hitler had post-encephalitic Parkinsonism.

    PubMed

    Lieberman, A

    1996-04-01

    Adolf Hitler had Parkinson symptoms in 1934, at age 45 years. He may have had transient symptoms in 1923, at age 34 years. Young-onset parkinsonism, during the 1920s, favored a diagnosis of post-encephalitic rather than idiopathic parkinsonism. Hitler had oculogyric crises, phenomena only associated with post-encephalitic parkinsonism. In addition, he had dystonic facial spasms, palilalia and a sleep disorder, phenomena more likely to be associated with post-encephalitic than idiopathic parkinsonism. In November 1918, at age 29 years, Hitler may have had von Economo's encephalitis, while he was a patient in a hospital, recovering from poison gas. This paper looks at the possible relationship of von Economo's encephalitis to Hitler's asocial behavior; his obsessions and compulsions, his cruelty and rages. The influence of Hitler's parkinsonism on his conduct during World War II is discussed.

  10. Iraq: Post-Saddam Governance and Security

    DTIC Science & Technology

    2006-06-14

    11 Commission Report, p. 66. 20 Deyoung, Karen, and Daniel Williams, “Training of Iraqi Exiles Authorized,” Washington Post, Oct. 19, 2002. 21...Williams, Daniel . “U.S. Army to Train 1,000 Iraqi Exiles,” Washington Post, Dec. 18, 2002. ! Links to Al Qaeda. Iraq was designated a state sponsor of...Office (IRMO).” IRMO, headed since June 2005 by Daniel Speckhard, has about 150 U.S. civilian personnel working out of four major centers around Iraq

  11. Non-linear Post Processing Image Enhancement

    NASA Technical Reports Server (NTRS)

    Hunt, Shawn; Lopez, Alex; Torres, Angel

    1997-01-01

    A non-linear filter for image post processing based on the feedforward Neural Network topology is presented. This study was undertaken to investigate the usefulness of "smart" filters in image post processing. The filter has shown to be useful in recovering high frequencies, such as those lost during the JPEG compression-decompression process. The filtered images have a higher signal to noise ratio, and a higher perceived image quality. Simulation studies comparing the proposed filter with the optimum mean square non-linear filter, showing examples of the high frequency recovery, and the statistical properties of the filter are given,

  12. Chemical scavenging of post-consumed clothes.

    PubMed

    Barot, Amit A; Sinha, Vijay Kumar

    2015-12-01

    Aiming toward the rectification of fiber grade PET waste accumulation as well as recycling and providing a technically viable route leading to preservation of the natural resources and environment, the post consumed polyester clothes were chemically recycled. Post consumed polyester clothes were recycled into bis(2-hydroxyethyl) terephthalate (BHET) monomer in the presence of ethylene glycol as depolymerising agent and zinc acetate as catalyst. Depolymerized product was characterized by chemical as well as analytical techniques. The fiber grade PET was eventually converted into BHET monomer with nearly 90% yield by employing 1% catalyst concentration and at optimum temperature of 180°C without mechanical input of stirring condition.

  13. Characteristics of post-transcriptional gene silencing.

    PubMed

    Chicas, A; Macino, G

    2001-11-01

    A number of gene silencing phenomena that inactivate genes at the post-transcriptional level have been identified. Due to its potential for studying gene function, post-transcriptional gene silencing (PTGS) has become an intense area of research. In this review we describe the different means of inducing PTGS and discuss the possible biological roles of these artificially induced phenomena. We also discuss other features of PTGS such as the mechanism of mRNA degradation, the nature of the silencing signal and the mechanism of PTGS inhibition by viral proteins.

  14. Characteristics of post-transcriptional gene silencing

    PubMed Central

    Chicas, Agustin; Macino, Giuseppe

    2001-01-01

    A number of gene silencing phenomena that inactivate genes at the post-transcriptional level have been identified. Due to its potential for studying gene function, post-transcriptional gene silencing (PTGS) has become an intense area of research. In this review we describe the different means of inducing PTGS and discuss the possible biological roles of these artificially induced phenomena. We also discuss other features of PTGS such as the mechanism of mRNA degradation, the nature of the silencing signal and the mechanism of PTGS inhibition by viral proteins. PMID:11713190

  15. Generator stator core vent duct spacer posts

    DOEpatents

    Griffith, John Wesley; Tong, Wei

    2003-06-24

    Generator stator cores are constructed by stacking many layers of magnetic laminations. Ventilation ducts may be inserted between these layers by inserting spacers into the core stack. The ventilation ducts allow for the passage of cooling gas through the core during operation. The spacers or spacer posts are positioned between groups of the magnetic laminations to define the ventilation ducts. The spacer posts are secured with longitudinal axes thereof substantially parallel to the core axis. With this structure, core tightness can be assured while maximizing ventilation duct cross section for gas flow and minimizing magnetic loss in the spacers.

  16. Split-resonator integrated-post MEMS gyroscope

    NASA Technical Reports Server (NTRS)

    Bae, Youngsam (Inventor); Hayworth, Ken J. (Inventor); Shcheglov, Kirill V. (Inventor)

    2004-01-01

    A split-resonator integrated-post vibratory microgyroscope may be fabricated using micro electrical mechanical systems (MEMS) fabrication techniques. The microgyroscope may include two gyroscope sections bonded together, each gyroscope section including resonator petals, electrodes, and an integrated half post. The half posts are aligned and bonded to act as a single post.

  17. 40 CFR 258.61 - Post-closure care requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Post-closure care requirements. 258.61... FOR MUNICIPAL SOLID WASTE LANDFILLS Closure and Post-Closure Care § 258.61 Post-closure care requirements. (a) Following closure of each MSWLF unit, the owner or operator must conduct post-closure...

  18. 49 CFR 663.31 - Post-delivery audit requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 7 2011-10-01 2011-10-01 false Post-delivery audit requirements. 663.31 Section... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PRE-AWARD AND POST-DELIVERY AUDITS OF ROLLING STOCK PURCHASES Post-Delivery Audits § 663.31 Post-delivery audit requirements. A recipient purchasing revenue service...

  19. 49 CFR 663.31 - Post-delivery audit requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 7 2010-10-01 2010-10-01 false Post-delivery audit requirements. 663.31 Section... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PRE-AWARD AND POST-DELIVERY AUDITS OF ROLLING STOCK PURCHASES Post-Delivery Audits § 663.31 Post-delivery audit requirements. A recipient purchasing revenue service...

  20. Development of Norms for the Post-deployment Reintegration Scale

    DTIC Science & Technology

    2010-09-01

    perspective. Recognizing the importance of successful post-deployment reintegration to optimal operational readiness, Canadian military researchers...of successful post-deployment reintegration to optimal operational readiness, Canadian military researchers developed the Army Post- Deployment... successful post-deployment reintegration to optimal operational readiness, and attempting to address the gaps and limitations of existing

  1. English Literatures in Post-Colonial Singapore

    ERIC Educational Resources Information Center

    Dass, Rozita

    2015-01-01

    The emergence of a vibrant literary, culture and arts scene promotes Singapore's claims as a hub for arts and culture in the Asian region, and as a global arts city by the 21st century. The richness and variety of Singapore literature from the early post-colonial years are evident in the evolution of a Singapore literary culture. The diaspora of…

  2. Social Movements in Post-Revolutionary Iran

    DTIC Science & Technology

    2013-12-01

    Iranian revolution, itself, planted their seeds in post-revolutionary Iran by its outcomes, which created political opportunities, mobilizing ...Iran, Islamic Republic of Iran, Iranian Domestic Politics, Social Movements, Political Opportunities, Mobilizing Structures and Resources, Framing...political opportunities, mobilizing structures, resources, and framing. Social movements became an alternative way of political participation

  3. Post Colonial Perspectives on Education Policy Research

    ERIC Educational Resources Information Center

    van der Westhuizen, Gert J.

    2013-01-01

    The focus of this article is on the role and contribution of policy research in contexts of social transformation. With reference to education transformation policies in post-apartheid South Africa, the argument is developed that research studies vary in their contribution to change, as a function of the paradigmatic assumptions and methodological…

  4. Third LDEF Post-Retrieval Symposium Abstracts

    NASA Technical Reports Server (NTRS)

    Levine, Arlene S. (Compiler)

    1993-01-01

    This volume is a compilation of abstracts submitted to the Third Long Duration Exposure Facility (LDEF) Post-Retrieval Symposium. The abstracts represent the data analysis of the 57 experiments flown on the LDEF. The experiments include materials, coatings, thermal systems, power and propulsion, science (cosmic ray, interstellar gas, heavy ions, micrometeoroid, etc.), electronics, optics, and life science.

  5. Post-traumatic unilateral plantar hyperhidrosis.

    PubMed

    Eren, Y; Yavasoglu, N G; Comoglu, S S

    2016-02-01

    Localized unilateral hyperhidrosis is rare and poorly understood, sometimes stemming from trauma. Feet, quite vulnerable to trauma are affected by disease-mediated plantar hyperhidrosis, usually bilaterally. This report describes partial hyperhidrosis developing post-traumatically on the left plantar region of a 52-year-old male.

  6. 10 CFR 73.75 - Posting.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Posting. 73.75 Section 73.75 Energy NUCLEAR REGULATORY... conversion, or nuclear fuel fabrication facilities. (b)(1) Licensees or certificate holders operating... a protected area that nonetheless contain special nuclear material, byproduct material, or...

  7. SMAP Post-launch Field Campaign Planning

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The SMAP post-launch Cal/Val activities are intended both to assess the quality of the mission products and to support analyses that lead to their improvement. A suite of complementary methodologies will be employed that will result in a robust global assessment. Much of the work will occur in the C...

  8. Post-Secondary Students' Purposes for Blogging

    ERIC Educational Resources Information Center

    Leslie, Paul; Murphy, Elizabeth

    2008-01-01

    The goal of the study was to explore post-secondary students' purposes for blogging with particular attention to the social and instructional purposes. The sample of blogs came from an all-women's college in the United Arab Emirates. Content analysis was conducted on eight blogs using previously tested instruments to identify social presence and…

  9. Language Situation in Post-War Sudan

    ERIC Educational Resources Information Center

    Siddiek, Ahmed Gumaa

    2010-01-01

    The theme behind this paper is to review the language policy and language planning in the Sudan, after the institutionalization of peace; by exploring the recent policy of political factions in the North and the South towards languages in post-war Sudan. This effort aims at encouraging non-Arabic speaking-ethnic-groups to accept the Arabic…

  10. Iron incorporation and post-malaria anaemia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Iron supplementation is employed to treat post-malarial anaemia in environments where iron deficiency is common. Malaria induces an intense inflammatory reaction that stalls reticulo-endothelial macrophagal iron recycling from haemolysed red blood cells and inhibits oral iron absorption, but the mag...

  11. Learning Systems in Post-Statutory Education

    ERIC Educational Resources Information Center

    Catherall, Paul

    2008-01-01

    This article examines the broad scope of systemised learning (e-learning) in post-statutory education. Issues for discussion include the origins and forms of learning systems, including technical and educational concepts and approaches, such as distributed and collaborative learning. The VLE (Virtual Learning Environment) is defined as the…

  12. Post-development image intensification by autoradiography

    NASA Technical Reports Server (NTRS)

    Askins, B. S.; Craven, P. D.; Odell, C. R.

    1979-01-01

    A method of post-development intensification of photographic images using a newly developed autoradiographic procedure is described. Radioactive Thiourea-S35 is combined with silver in the developed emulsion, which is then contact printed with a receiver emulsion. The beta decay from S35 produces an enhanced autoradiographic image. The laboratory technique is described and results of astronomical applications are presented.

  13. Post-traumatic knee stiffness: surgical techniques.

    PubMed

    Pujol, N; Boisrenoult, P; Beaufils, P

    2015-02-01

    Post-traumatic knee stiffness and loss of range of motion is a common complication of injuries to the knee area. The causes of post-traumatic knee stiffness can be divided into flexion contractures, extension contractures, and combined contractures. Post-traumatic stiffness can be due to the presence of dense intra-articular adhesions and/or fibrotic transformation of peri-articular structures. Various open and arthroscopic surgical treatments are possible. A precise diagnosis and understanding of the pathology is mandatory prior to any surgical treatment. Failure is imminent if all pathologies are not addressed correctly. From a general point of view, a flexion contracture is due to posterior adhesions and/or anterior impingement. On the other hand, extension contractures are due to anterior adhesions and/or posterior impingement. This overview will describe the different modern surgical techniques for treating post-traumatic knee stiffness. Any bony impingements must be treated before soft tissue release is performed. Intra-articular stiff knees with a loss of flexion can be treated by an anterior arthroscopic arthrolysis. Extra-articular pathology causing a flexion contracture can be treated by open or endoscopic quadriceps release. Extension contractures can be treated by arthroscopic or open posterior arthrolysis. Postoperative care (analgesia, rehabilitation) is essential to maintaining the range of motion obtained intra-operatively.

  14. 49 CFR 238.213 - Corner posts.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... inward. (b)(1) Except as provided in paragraph (c) of this section, each cab car and MU locomotive...-telescoping plate (if used), or of its supporting car body structure. (c)(1) Each cab car and MU locomotive... cab car and MU locomotive may have two corner posts on the opposite (non-operating) side of the...

  15. 49 CFR 238.213 - Corner posts.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... inward. (b)(1) Except as provided in paragraph (c) of this section, each cab car and MU locomotive...-telescoping plate (if used), or of its supporting car body structure. (c)(1) Each cab car and MU locomotive... cab car and MU locomotive may have two corner posts on the opposite (non-operating) side of the...

  16. 49 CFR 238.213 - Corner posts.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... inward. (b)(1) Except as provided in paragraph (c) of this section, each cab car and MU locomotive...-telescoping plate (if used), or of its supporting car body structure. (c)(1) Each cab car and MU locomotive... cab car and MU locomotive may have two corner posts on the opposite (non-operating) side of the...

  17. 49 CFR 238.213 - Corner posts.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... inward. (b)(1) Except as provided in paragraph (c) of this section, each cab car and MU locomotive...-telescoping plate (if used), or of its supporting car body structure. (c)(1) Each cab car and MU locomotive... cab car and MU locomotive may have two corner posts on the opposite (non-operating) side of the...

  18. 49 CFR 238.213 - Corner posts.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... inward. (b)(1) Except as provided in paragraph (c) of this section, each cab car and MU locomotive...-telescoping plate (if used), or of its supporting car body structure. (c)(1) Each cab car and MU locomotive... cab car and MU locomotive may have two corner posts on the opposite (non-operating) side of the...

  19. Post-soldering of nonprecious alloys.

    PubMed

    Saxton, P L

    1980-05-01

    A repeatable post-soldering technique for a nonprecious alloy has been described. With proper metal design, nonprecious alloy crowns can be soldered in a standard vacuum porcelain furnace. Scanning electron micrographs and EDXA confirm that a good union has taken place between the gold solder and nickel alloy.

  20. 43 CFR 3861.7 - Posting.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Posting. 3861.7 Section 3861.7 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) MINERAL PATENT APPLICATIONS Surveys and Plats §...

  1. 43 CFR 3861.7 - Posting.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Posting. 3861.7 Section 3861.7 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) MINERAL PATENT APPLICATIONS Surveys and Plats §...

  2. 43 CFR 3861.7 - Posting.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Posting. 3861.7 Section 3861.7 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) MINERAL PATENT APPLICATIONS Surveys and Plats §...

  3. 43 CFR 3861.7 - Posting.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Posting. 3861.7 Section 3861.7 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) MINERAL PATENT APPLICATIONS Surveys and Plats §...

  4. Post stapedotomy aviation: A changing scenario.

    PubMed

    Rajguru, Renu

    2014-01-01

    Aeromedical implications of stapedotomy like rapid barometric changes and G forces are generally thought to put an end to the aviation career of an aviator. Aviation industry has grown tremendously in the last few decades, and aviation now is not only occupational but also recreational. The Indian Military Aviation rules state that, "Stapedectomy cases will be assessed permanently unfit for flying duties. These cases will be cautioned against flying in an unpressurised aircraft." The basis of this is the aeromedical concerns associated with stapedotomy as clinical conditions which are of minor significance on the ground may become aggravated in the air. With an ever expanding civil and military aviation industry, the number of aviators who have undergone stapedotomy has also increased. Though grounding the aircrew is the safest option, but if medical certification is denied to all, then the majority who can fly safely will also be excluded, thus denying the organization of its trained resources. This paper discusses post otosclerosis and post stapedotomy aeromedical concerns, reviews existing literature concerning post stapedotomy aviation and various post stapedotomy aviation policies.

  5. Post-natal myogenic and adipogenic developmental

    PubMed Central

    Konings, Gonda; van Weeghel, Michel; van den Hoogenhof, Maarten MG; Gijbels, Marion; van Erk, Arie; Schoonderwoerd, Kees; van den Bosch, Bianca; Dahlmans, Vivian; Calis, Chantal; Houten, Sander M; Misteli, Tom

    2011-01-01

    A-type lamins are a major component of the nuclear lamina. Mutations in the LMNA gene, which encodes the A-type lamins A and C, cause a set of phenotypically diverse diseases collectively called laminopathies. While adult LMNA null mice show various symptoms typically associated with laminopathies, the effect of loss of lamin A/C on early post-natal development is poorly understood. Here we developed a novel LMNA null mouse (LMNAGT−/−) based on genetrap technology and analyzed its early post-natal development. We detect LMNA transcripts in heart, the outflow tract, dorsal aorta, liver and somites during early embryonic development. Loss of A-type lamins results in severe growth retardation and developmental defects of the heart, including impaired myocyte hypertrophy, skeletal muscle hypotrophy, decreased amounts of subcutaneous adipose tissue and impaired ex vivo adipogenic differentiation. These defects cause death at 2 to 3 weeks post partum associated with muscle weakness and metabolic complications, but without the occurrence of dilated cardiomyopathy or an obvious progeroid phenotype. Our results indicate that defective early post-natal development critically contributes to the disease phenotypes in adult laminopathies. PMID:21818413

  6. 10 CFR 73.75 - Posting.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... facilities described in paragraph (a) of this section that have a protected area shall conspicuously post notices at every vehicle and pedestrian entrance to the protected area. (2) Licensees or certificate... a protected area that nonetheless contain special nuclear material, byproduct material, or...

  7. Post Separation Adjustment and Women's Liberation.

    ERIC Educational Resources Information Center

    Worthington, Elliot R.

    The interaction between post separation adjustment for reunited military families and the Women's Liberation Movement is a complex occurrence which is beginning to have a profound effect on some military families. Two forces are acting upon wives of servicemen that subject marriages to conflicts previously unheard of. One force is the critical…

  8. The Post 9/11 English Teacher

    ERIC Educational Resources Information Center

    English Journal, 2005

    2005-01-01

    An English teacher offers his thoughts on what they could learn about their role in the post 9/11-world and suggests reflecting on the events of the incident as professionals. The 9/11 Commission Report defines an important role for education and recommends US funding to improve public education, vocational education, and halving adult illiteracy…

  9. Adolescent Post-Traumatic Stress Disorder

    ERIC Educational Resources Information Center

    Yule, William

    2003-01-01

    Based on over a decade of work in the area of PTSD, including a longitudinal study of PTSD among adolescents, Dr. Yule provides an introduction to post-traumatic stress disorder as it occurs in youth. This includes a look at the manifestations of stress reactions, the incidence and prevalence of PTSD, and the relationship between levels of…

  10. Intrastromal crosslinking in post-LASIK ectasia.

    PubMed

    Moscovici, Bernardo Kaplan; Campos, Mauro

    2014-01-01

    We describe a case of early post-LASIK ectasia detected in the first 6 months after surgery. The patient was treated by means of intrastromal corneal crosslinking under the flap, without de-epithelialization, which resulted in a positive outcome. At the time of writing, 2 years after the procedure, the patient remained free of progression.

  11. 76 FR 44053 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-22

    ... From the Federal Register Online via the Government Publishing Office ] POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the La Mesa Annex, CA Station has been filed....

  12. 75 FR 78777 - Post Office Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-16

    ... From the Federal Register Online via the Government Publishing Office POSTAL REGULATORY COMMISSION Post Office Closing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: This document informs the public that an appeal of the closing of the Penobscot Finance Station in Detroit, Michigan...

  13. Provoking Reflective Thinking in Post Observation Conversations

    ERIC Educational Resources Information Center

    Kim, Younhee; Silver, Rita Elaine

    2016-01-01

    We present a micro-analysis of post observation conversations between classroom teachers and mentors. Using the approach of conversation analysis, we show how the sequential organization of an episode (i.e., who initiates the interaction, question format used by mentors) could potentially serve to provoke or hinder teacher reflection. Our analysis…

  14. Shakespeare for the Post-Postmodern Age.

    ERIC Educational Resources Information Center

    Leech, Carolyn

    Labeling literary or artistic periods is always tricky, and labeling an emerging period (such as this post-postmodern one) is, of course, impossible. Harold Bloom has labeled this period the "chaotic age" because of the canon wars that have raged among factions. One writer with a place in any canon and who is an anodyne to the chaos of…

  15. Post-encephalitic Parkinsonism: current experience

    PubMed Central

    Rail, David; Scholtz, Carl; Swash, Michael

    1981-01-01

    The diagnosis of post-encephalitic Parkinsonism is rarely entertained today. In this paper we discuss eight recent patients, six of whom presented in the last 20 years, that conform to the diagnosis of encephalitis lethargica. The clinical features by which the diagnosis may be made are defined so that a contemporary definition of this disorder may be attained. Images PMID:7299406

  16. Post-Compulsory Education for Disabled People.

    ERIC Educational Resources Information Center

    Organisation for Economic Cooperation and Development, Paris (France). Centre for Educational Research and Innovation.

    This report presents findings of a 3-year study (1994-1997) of post-compulsory educational opportunities for adolescents and adults with disabilities in 10 European countries (Finland, France, Iceland, Ireland, Italy, the Netherlands, Norway, Spain, Sweden, United Kingdom), Australia, and the Canadian provinces of British Columbia and Quebec. It…

  17. Post-Keynesian Theory: An Overview.

    ERIC Educational Resources Information Center

    Kregel, J. A.

    1983-01-01

    The evolution and current position of post-Keynesian economic theory are examined. The theory is based on Keynes' exposition of effective demand in a monetary production economy determining the level of employment, rather than through supply and demand in the "real" and "monetary" sectors determining the level of real output.…

  18. Polio and Post-Polio Syndrome

    MedlinePlus

    Polio is an infectious disease caused by a virus. The virus lives in an infected person's throat and intestines. It is most often spread by contact with the stool of an infected person. You can also get it from droplets ... the paralysis of polio. Some people who've had polio develop post- ...

  19. Post stapedotomy aviation: A changing scenario

    PubMed Central

    Rajguru, Renu

    2014-01-01

    Aeromedical implications of stapedotomy like rapid barometric changes and G forces are generally thought to put an end to the aviation career of an aviator. Aviation industry has grown tremendously in the last few decades, and aviation now is not only occupational but also recreational. The Indian Military Aviation rules state that, “Stapedectomy cases will be assessed permanently unfit for flying duties. These cases will be cautioned against flying in an unpressurised aircraft.” The basis of this is the aeromedical concerns associated with stapedotomy as clinical conditions which are of minor significance on the ground may become aggravated in the air. With an ever expanding civil and military aviation industry, the number of aviators who have undergone stapedotomy has also increased. Though grounding the aircrew is the safest option, but if medical certification is denied to all, then the majority who can fly safely will also be excluded, thus denying the organization of its trained resources. This paper discusses post otosclerosis and post stapedotomy aeromedical concerns, reviews existing literature concerning post stapedotomy aviation and various post stapedotomy aviation policies. PMID:25598613

  20. The Kurds in Post-Saddam Iraq

    DTIC Science & Technology

    2009-04-06

    Kurds in Post-Saddam Iraq Congressional Research Service 3 The TAL did not give the Kurds control of Kirkuk ( Tamim province),2 instead setting up a...Disputed Territories, and Minorities in the North The Iraqi Kurds’ vehement insistence that Kirkuk/ Tamim and some cities in Diyala and Nineveh provinces

  1. The Post-Tenure-Review Blues

    ERIC Educational Resources Information Center

    Reeves, Thomas C.

    2004-01-01

    Damp Valley U granted Jeff tenure after six years. Then, four years later, he found himself sweating through a post-tenure interrogation. The damning charges: uttering the word "foreman," involvement with a men's group, failure to note that 50 percent of cowgirls were black. Thomas Reeves enumerates the punishment meted out to his white male…

  2. 39 CFR 241.1 - Post offices.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 39 Postal Service 1 2014-07-01 2014-07-01 false Post offices. 241.1 Section 241.1 Postal Service UNITED STATES POSTAL SERVICE ORGANIZATION AND ADMINISTRATION ESTABLISHMENT CLASSIFICATION, AND... ensure that regular and effective postal services are available to all customers within...

  3. 39 CFR 241.1 - Post offices.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 39 Postal Service 1 2013-07-01 2013-07-01 false Post offices. 241.1 Section 241.1 Postal Service UNITED STATES POSTAL SERVICE ORGANIZATION AND ADMINISTRATION ESTABLISHMENT CLASSIFICATION, AND... ensure that regular and effective postal services are available to all customers within...

  4. Reviewing post-publication peer review

    PubMed Central

    Knoepfler, Paul

    2015-01-01

    Post-publication peer review (PPPR) is transforming how the life sciences community evaluates published manuscripts and data. Unsurprisingly, however, PPPR is experiencing growing pains, and some elements of the process distinct from standard pre-publication review remain controversial. I discuss the rapid evolution of PPPR, its impact, and the challenges associated with it. PMID:25851694

  5. Microgyroscope with Vibrating Post as Rotation Transducer

    NASA Technical Reports Server (NTRS)

    Tang, Tony K.; Gutierrez, Roman

    2003-01-01

    The figure depicts a micromachined silicon vibratory gyroscope that senses rotation about its z axis. The rotation-sensitive vibratory element is a post oriented (when at equilibrium) along the z axis and suspended at its base by thin, flexible silicon bands oriented along the x and y axes, respectively. Unlike in the vibratory microgyroscopes described in the immediately preceding article ["Cloverleaf Vibratory Microgyroscope With Integrated Post" (NPO-20688)] and other previous articles in NASA Tech Briefs, the rotation-sensitive vibratory element does not include a cloverleaf-shaped structure that lies (when at equilibrium) in the x-y plane. As in the cases of the previously reported vibratory microgyroscopes, vibrations of the rotation-sensitive vibratory element are excited electrostatically, the vibrations are measured by use of capacitive proximity sensors, and the rate of rotation along the axis of sensitivity is deduced from the effect of the Coriolis force upon the vibrations. To create electrodes for electrostatic excitation and capacitive sensing of vibrations, portions of the facing surfaces of the post and of the four stationary members that surround the post are rendered electrically conductive; this can be accomplished by either depositing metal films or else doping the silicon in the affected areas.

  6. Welcome to the Post-Bachelor's World

    ERIC Educational Resources Information Center

    Gallagher, Sean

    2016-01-01

    Post-baccalaureate education has emerged as one of the fastest growing segments of higher education. Over the past decade, master's degree enrollment in the U.S. has grown 35%--and the share of adults that hold a master's degree has gone from less than 7% to nearly 9% of the population. Keeping the supply and demand dynamics of basic economic…

  7. Context specificity of post-error and post-conflict cognitive control adjustments.

    PubMed

    Forster, Sarah E; Cho, Raymond Y

    2014-01-01

    There has been accumulating evidence that cognitive control can be adaptively regulated by monitoring for processing conflict as an index of online control demands. However, it is not yet known whether top-down control mechanisms respond to processing conflict in a manner specific to the operative task context or confer a more generalized benefit. While previous studies have examined the taskset-specificity of conflict adaptation effects, yielding inconsistent results, control-related performance adjustments following errors have been largely overlooked. This gap in the literature underscores recent debate as to whether post-error performance represents a strategic, control-mediated mechanism or a nonstrategic consequence of attentional orienting. In the present study, evidence of generalized control following both high conflict correct trials and errors was explored in a task-switching paradigm. Conflict adaptation effects were not found to generalize across tasksets, despite a shared response set. In contrast, post-error slowing effects were found to extend to the inactive taskset and were predictive of enhanced post-error accuracy. In addition, post-error performance adjustments were found to persist for several trials and across multiple task switches, a finding inconsistent with attentional orienting accounts of post-error slowing. These findings indicate that error-related control adjustments confer a generalized performance benefit and suggest dissociable mechanisms of post-conflict and post-error control.

  8. Cryptococcal meningitis post autologous stem cell transplantation.

    PubMed

    Chaaban, S; Wheat, L J; Assi, M

    2014-06-01

    Disseminated Cryptococcus disease occurs in patients with defective T-cell immunity. Cryptococcal meningitis following autologous stem cell transplant (SCT) has been described previously in only 1 patient, 4 months post SCT and while off antifungal prophylaxis. We present a unique case of Cryptococcus meningitis pre-engraftment after autologous SCT, while the patient was receiving fluconazole prophylaxis. A 41-year-old man with non-Hodgkin's lymphoma underwent autologous SCT. Post-transplant prophylaxis consisted of fluconazole 400 mg daily, levofloxacin 500 mg daily, and acyclovir 800 mg twice daily. On day 9 post transplant, he developed fever and headache. Peripheral white blood cell count (WBC) was 700/μL. Magnetic resonance imaging of the brain showed lesions consistent with meningoencephalitis. Cerebrospinal fluid (CSF) analysis revealed a WBC of 39 with 77% lymphocytes, protein 63, glucose 38, CSF pressure 20.5 cmH2 O, and a positive cryptococcal antigen. CSF culture confirmed Cryptococcus neoformans. The patient was treated with liposomal amphotericin B 5 mg/kg intravenously daily, and flucytosine 37.5 mg/kg orally every 6 h. He was switched to fluconazole 400 mg daily after 3 weeks of amphotericin therapy, with sterilization of the CSF with negative CSFCryptococcus antigen and negative CSF culture. Review of the literature revealed 9 cases of cryptococcal disease in recipients of SCT. Median time of onset was 64 days post transplant. Only 3 meningitis cases were described; 2 of them after allogeneic SCT. Fungal prophylaxis with fluconazole post autologous SCT is recommended at least through engraftment, and for up to 100 days in high-risk patients. A high index of suspicion is needed to diagnose and treat opportunistic infections, especially in the face of immunosuppression and despite adequate prophylaxis. Infection is usually fatal without treatment, thus prompt diagnosis and therapy might be life saving.

  9. Post-Slavery? Post-Segregation? Post-Racial? A History of the Impact of Slavery, Segregation, and Racism on the Education of African Americans

    ERIC Educational Resources Information Center

    Span, Christopher M.

    2015-01-01

    This chapter details how slavery, segregation, and racism impacted the educational experiences of African Americans from the colonial era to the present. It argues that America has yet to be a truly post-slavery and post-segregation society, let alone a post-racial society.

  10. Post-Polio Directory 2014: Post-Polio Clinics, Health Professionals, Support Groups

    MedlinePlus

    ... Siegel, MD Rush University Medical Center 1725 W Harrison St Ste 1106 Chicago, IL 60612-3841 312- ... Michigan Post-Polio Support Group Ethel Jean Iutzi Harrison 989-539-3781, hnjutzi12@ejourney.com Lansing Area ...

  11. Effects of post surface conditioning before silanization on bond strength between fiber post and resin cement

    PubMed Central

    Ranjbarian, Parisa

    2013-01-01

    PURPOSE Post surface conditioning is necessary to expose the glass fibers to enable bonding between fiber post and resin cement. The purpose of the present study was to evaluate the effect of different surface conditioning on tensile bond strength (TBS) of a glass fiber reinforced post to resin cement. MATERIALS AND METHODS In this in vitro study, 40 extracted single canal central incisors were endodontically treated and post spaces were prepared. The teeth were divided into four groups according to the methods of post surface treatment (n=10): 1) Silanization after etching with 20% H2O2, 2) Silanization after airborne-particle abrasion, 3) Silanization, and 4) No conditioning (Control). Adhesive resin cement (Panavia F 2.0) was used for cementation of the fiber posts to the root canal dentin. Three slices of 3 mm thick were obtained from each root. A universal testing machine was used with a cross-head speed of 1 mm/minute for performing the push-out tests. Two-way ANOVA and Tukey post hoc tests were used for analyzing data (α=0.05). RESULTS It is revealed that different surface treatments and root dentin regions had significant effects on TBS, but the interaction between surface treatments and root canal regions had no significant effect on TBS. There was significant difference among H2O2 + Silane Group and other three groups. CONCLUSION There were significant differences among the mean TBS values of different surface treatments. Application of hydrogen peroxide before silanization increased the bond strength between resin cements and fiber posts. The mean TBS mean values was significantly greater in the coronal region of root canal than the middle and apical thirds. PMID:23755337

  12. Focus on the post-DVD formats

    NASA Astrophysics Data System (ADS)

    He, Hong; Wei, Jingsong

    2005-09-01

    As the digital TV(DTV) technologies are developing rapidly on its standard system, hardware desktop, software model, and interfaces between DTV and the home net, High Definition TV (HDTV) program worldwide broadcasting is scheduled. Enjoying high quality TV program at home is not a far-off dream for people. As for the main recording media, what would the main stream be for the optical storage technology to meet the HDTV requirements is becoming a great concern. At present, there are a few kinds of Post-DVD formats which are competing on technology, standard and market. Here we give a review on the co-existing Post-DVD formats in the world. We will discuss on the basic parameters for optical disk, video /audio coding strategy and system performance for HDTV program.

  13. A Long-Range Video Observation Post

    SciTech Connect

    Arlowe, D.

    1995-07-01

    The Long Range Video Observation Post (LRVOP) Project is a cooperative effort between the US and a Middle Eastern country to develop an improved version of their current video observation post. This project is part of a larger effort to cooperatively develop anti-terrorist technology. This particular equipment is required to facilitate the recording and identification of humans at a range of 1000 meters in day-light and 500 meters at night. The project objective was to take advantage of recent advances in camera technology, recorders, and image processing to provide an significant increase in performance with only a minimum increase in size, weight, and cost. The goal of the project was to convert the users general needs and desires into specific requirements that could be bid on by several companies. This paper covers the specific performance requirements, generally describe the components that might be used, and concentrate on describing the more difficult issues and technical challenges.

  14. Galanin's implications for post-stroke improvement

    PubMed Central

    Song, Juhyun

    2016-01-01

    Stroke leads to a variety of pathophysiological conditions such as ischemic infarct, cerebral inflammation, neuronal damage, cognitive decline, and depression. Many endeavors have been tried to find the therapeutic solutions to attenuate severe neuropathogenesis after stroke. Several studies have reported that a decrease in the neuropeptide regulator ‘galanin’ is associated with neuronal loss, learning and memory dysfunctions, and depression following a stroke. The present review summarized recent evidences on the function and the therapeutic potential of galanin in post-ischemic stroke to provide a further understanding of galanin's role. Hence, we suggest that galanin needs to be considered as a therapeutic factor in the alleviation of post-stroke pathologies. PMID:28127496

  15. VLAP: results immediately post-op

    NASA Astrophysics Data System (ADS)

    Cowles, Robert S.

    1996-05-01

    Visual laser ablation of the prostate (VLAP) has been shown to be as effective with fewer complications than TURP in the treatment of bladder outlet obstruction secondary to benign prostatic hyperplasia. Questions have been raised about VLAP regarding prolonged irritative and obstructive voiding symptoms postoperatively. It is postulated that these symptoms are due to the slow slough of necrotic debris following VLAP. In an effort to improve upon the technique of VLAP, patients underwent lasing of the prostate in the routine manner (2, 4, 8, and 10 o'clock positions with sixty watts for sixty seconds) using Nd:YAG free beam energy. A bladder neck incision was then performed using a contact laser fiber. International prostate symptom score assessments were done preoperatively; one week and six weeks postoperatively. Post void residual urine volumes and prostate size were also evaluated. The findings indicate that symptom scores and post void residual urine volumes have significantly improved within ten days postoperatively using this technique.

  16. Post-abortion syndrome: creating an affliction.

    PubMed

    Dadlez, E M; Andrews, William L

    2010-11-01

    The contention that abortion harms women constitutes a new strategy employed by the pro-life movement to supplement arguments about fetal rights. David C. Reardon is a prominent promoter of this strategy. Post-abortion syndrome purports to establish that abortion psychologically harms women and, indeed, can harm persons associated with women who have abortions. Thus, harms that abortion is alleged to produce are multiplied. Claims of repression are employed to complicate efforts to disprove the existence of psychological harm and causal antecedents of trauma are only selectively investigated. We argue that there is no such thing as post-abortion syndrome and that the psychological harms Reardon and others claim abortion inflicts on women can usually be ascribed to different causes. We question the evidence accumulated by Reardon and his analysis of data accumulated by others. Most importantly, we question whether the conclusions Reardon has drawn follow from the evidence he cites.

  17. [Poliomyelitis and the post-polio syndrome].

    PubMed

    Dénes, Z; Varga, M

    2001-07-15

    In developed countries as well as in Hungary polio virus related disease disappeared completely due to the extensive administering of vaccine. As a result, young and middle-aged doctors have no experience of encountering acute polio virus infection but instead they meet its resultant impairments and disabilities. Persons who had suffered the onset of poliomyelitis 3 or 4 decades earlier, may to develop a new set of symptoms and functional declines. The criteria for post-polio syndrome were identified and its impairments and disabilities were described. It is only within the last decade that the adaptive changes in muscular tissue, insufficiently compensed denervation, together with the effects of physiotherapy, have become better known. The aim of this paper is to review the present situation concerning the struggle for keeping the polio virus in check, to give a short summary of the post-polio syndrome and to draw attention to the importance of rehabilitation.

  18. Endometritis: Managing Persistent Post-Breeding Endometritis.

    PubMed

    Canisso, Igor F; Stewart, Jamie; Coutinho da Silva, Marco A

    2016-12-01

    Endometritis was rated as the third most common medical problem encountered in adult horses in North America. It is the leading cause of subfertility in broodmares and is a major contributor to economic loss in the horse breeding industry, with pregnancy rates reported to be as low as 21% in mares with severe endometritis. Endometritis may be categorized as: endometrosis (chronic degenerative endometritis), acute, chronic, active, dormant, subclinical, clinical, and persistent post-breeding. These classifications are not mutually exclusive, and mares may change categories within breeding seasons or estrous cycles or may fit in multiple classifications. This chapter will focus on discussing etiology and management strategies for mares affected by persistent post-breeding endometritis. Overall, these mares are considered subfertile but acceptable pregnancy and foaling rates can be achieved with appropriate breeding management.

  19. Psychosocial Interventions Pre and Post Bariatric Surgery.

    PubMed

    Kalarchian, Melissa A; Marcus, Marsha D

    2015-11-01

    Despite positive results overall, a substantial number of patients experience poor long-term outcomes following bariatric surgery. One reason for variability in weight loss may be difficulty in making and sustaining changes in dietary intake and physical activity; post-surgery binge eating has also been associated with poorer weight outcomes. In this paper, we review available evidence on adjunctive psychosocial interventions for bariatric surgery patients. Although the literature is limited, evidence suggests that bariatric surgery patients may benefit from a comprehensive approach targeting diet, activity and psychological factors. We think the optimal time to initiate adjunctive intervention is after surgery, but before significant weight regain has occurred. Adaptive interventions incorporating advances in technology may prove to be effective for promoting behavioural self-management and psychosocial adjustment following bariatric surgery. For some patients, pharmacotherapy and reoperation may also play a role in a personalized approach to post-surgery care.

  20. PREDICTORS FOR POST- STROKE DELIRIUM OUTCOME

    PubMed Central

    Dostovic, Zikrija; Dostovic, Ernestina; Smajlovic, Dzevdet; Ibrahimagic, Omer C.; Avdic, Leila; Becirovic, Elvir

    2016-01-01

    Background: There have been only a small number of studies that have evaluated the outcome of post-stroke delirium. Objectives: To evaluate the effects of gender, age, stroke localization, delirium severity, previous illnesses, associated medical complications on delirium outcome as well as, to determine effects of delirium on cognitive functioning one year after stroke. Patients and Methods: Comprehensive neuropsychological assessments were performed within the first week of stroke onset, at hospital discharge, and followed-up for 3, 6 and 12 months after stroke. We used diagnostic tools such as Glazgow Coma Scale, Delirium Rating Scale, National Institutes of Health Stroke Scale and Mini-Mental State. Results: Patients who developed post-stroke delirium had significantly more complications (p = 0.0005). Direct logistic regression was performed to assess the impact of several factors on the likelihood that patients will die. The strongest predictor of outcome was age, mean age ≥ 65 years with a odds ratio (OR) 4.9. Cox’s regression survival was conducted to assess the impact of multiple factors on survival. The accompanying medical complications were the strongest predictor of respondents poore outcome with Hazard-risk 3.3. Cognitive assessments including Mini Mental State score have showen that post-stroke delirium patients had significant cognitive impairment, three (p = 0.0005), six months (p = 0.0005) and one year (p = 0.0005) after stroke, compared to patients without delirium. Conclusion: Patient gender, age, localization of stroke, severity of delirium, chronic diseases and emerging complications significantly affect the outcome of post- stroke delirium. Delirium significantly reduced cognitive functioning of after stroke patients. PMID:27999490

  1. Catecholamines in Post-Traumatic Stress Disorder

    DTIC Science & Technology

    2012-07-01

    could lead to memories that are too strong, contributing to the recurrent, intrusive retrieval of the traumatic events that occurs in PTSD. As a...emotionally arousing experiences are typically vivid and persistent. The recurrent, intrusive memories of traumatic events in post-traumatic stress disorder...signaling plays a critical role in the maintenance of waking and in the regulation of REM sleep. J Neurophysiol 92:2071–2082. Ouyang M, Zhang L, Zhu

  2. Space shuttle holddown post blast shield

    NASA Technical Reports Server (NTRS)

    Larracas, F. B.

    1991-01-01

    The original and subsequent designs of the Solid Rocket Booster/Holddown Post blast shield assemblies and their associated hardware are described. It presents the major problems encountered during their early use in the Space Shuttle Program, during the Return-to-Flight Modification Phase, and during their fabrication and validation testing phases. The actions taken to correct the problems are discussed, along with the various concepts now being considered to increase the useful life of the blast shield.

  3. Post-main-sequence planetary system evolution

    PubMed Central

    Veras, Dimitri

    2016-01-01

    The fates of planetary systems provide unassailable insights into their formation and represent rich cross-disciplinary dynamical laboratories. Mounting observations of post-main-sequence planetary systems necessitate a complementary level of theoretical scrutiny. Here, I review the diverse dynamical processes which affect planets, asteroids, comets and pebbles as their parent stars evolve into giant branch, white dwarf and neutron stars. This reference provides a foundation for the interpretation and modelling of currently known systems and upcoming discoveries. PMID:26998326

  4. Mt. Pinatubo Volcano - Post Eruption, Luzon, Philippines

    NASA Technical Reports Server (NTRS)

    1992-01-01

    Mt. Pinatubo on the island of Luzon (14.5N, 120.5E) erupted catastrophically in June 1991 after over 600 years of inactivity. Partially obscured by clouds in this post eruption photo, the crater is not obvious in this scene but the blowout area, in the once heavily forested region, is easily observed as lava flow, ash fallout, mud slide and debris trails mar the landscape. Clark AFB, once the crossroads of the SW Pacific can only partially be seen.

  5. PHMC post-NPH emergency response training

    SciTech Connect

    Conrads, T.J.

    1997-04-08

    This document describes post-Natural Phenomena Hazard (NPH) emergency response training that was provided to two teams of Project Hanford Management Contractors (PHMC) staff that will be used to assess potential structural damage that may occur as a result of a significant natural phenomena event. This training supports recent plans and procedures to use trained staff to inspect structures following an NPH event on the Hanford Site.

  6. Post senescent grass canopy remote sensing

    NASA Technical Reports Server (NTRS)

    Tucker, C. J.

    1978-01-01

    Analysis of in situ collected spectral reflectance data from a dormant or senescent grass canopy showed a direct relationship existed between spectral reflectance and biomass for the 0.50-0.80 micron spectral region. The data, collected four weeks after the end of the growing season, indicated that post senescent remote sensing of grass canopy biomass is possible and helps to elucidate the spectral contribution of recently dead vegetation in mixed live/dead canopy situations.

  7. Post Conflict Reconstruction: A Selected Bibliography

    DTIC Science & Technology

    2007-01-01

    2005) http:// www.csis.org/isp/ pcr /voa%5Freport.pdf Marshall, A. Phased Withdrawal, Conflict Resolution and State Reconstruction. Camberley, Surrey...115-215. Wilson OmniFile Wardak, Ali. “Building a Post-War Justice System in Afghanistan.” Crime , Law and Social Change 41 (May 2004): 319-341...240. Cambridge: Belknap Press of Harvard University Press, 2004. (CB251 .K26 2004) 17 Labs , Eric J. Paying for Iraq’s Reconstruction

  8. Post space preparation: an online study guide.

    PubMed

    2008-05-01

    The Editorial Board of the Journal of Endodontics has developed a literature-based study guide of topical areas related to endodontics. This study guide is intended to give the reader a focused review of the essential endodontic literature and does not cite all possible articles related to each topic. Although citing all articles would be comprehensive, it would defeat the idea of a study guide. This section will focus on post space preparation.

  9. Post-main-sequence planetary system evolution.

    PubMed

    Veras, Dimitri

    2016-02-01

    The fates of planetary systems provide unassailable insights into their formation and represent rich cross-disciplinary dynamical laboratories. Mounting observations of post-main-sequence planetary systems necessitate a complementary level of theoretical scrutiny. Here, I review the diverse dynamical processes which affect planets, asteroids, comets and pebbles as their parent stars evolve into giant branch, white dwarf and neutron stars. This reference provides a foundation for the interpretation and modelling of currently known systems and upcoming discoveries.

  10. Restorative Case Report: Flexibility of Fibre-Posts.

    PubMed

    Lancaster, Paula E

    2015-06-01

    Restoration of an anterior root-filled tooth with little remaining coronal tooth-tissue can utilise a post to retain a core, enabling definitive restoration. Post material was, until recently, primarily metal--be it cast or prefabricated. Currently, fibre-posts are promoted as being advantageous due to a favourable failure mechanism which may protect the root from fracture. This Case Report demonstrates failure of the structural integrity of a fibre-post in a maxillary lateral incisor, with a proposed explanation. Retreatment employed a diamond-coated ultrasonic tip for removal of the residual fibre-post and restoration with a cast-post and metal ceramic crown.

  11. Post-earthquake inspection of utility buildings

    SciTech Connect

    Matsuda, E.; Cluff, L.; Savage, W.; Poland, C.

    1995-12-31

    The evacuation of safe buildings and the inability to reoccupy them immediately after earthquakes can have significant impacts on lifeline utilities, including delays in the restoration of essential services. For many of Pacific Gas and Electric Company`s 3400 buildings, the potential for unnecessary evacuations and delays in reentry was judged unacceptable. A Post-Earthquake Investigation Program, developed jointly by PG and E and Degenkolb Engineers, facilitates the post-earthquake use of essential buildings. The details of the program were developed taking into consideration the effects of high-likelihood scenario earthquakes on PG and E facilities, and the potential disruption of transportation and communication systems. Qualified engineers were pre-assigned to inspect key facilities following prescribed earthquakes. The inspections will be facilitated by pre-earthquake evaluations and post-earthquake manuals. Building department personnel support the program, because it promotes the timely and accurate assessment of essential buildings within their jurisdiction. The program was developed for a gas and electric utility; however, it is applicable to other organizations in earthquake regions.

  12. Recurrent post-partum coronary artery dissection

    PubMed Central

    2010-01-01

    Coronary artery dissection is a rare but well-described cause for myocardial infarction during the post-partum period. Dissection of multiple coronary arteries is even less frequent. Here we present a case of recurrent post-partum coronary artery dissections. This unusual presentation poses unique problems for management. A 35 year-old female, gravida 3 para 2, presented with myocardial infarction 9 weeks and 3 days post-partum. Cardiac catheterization demonstrated left anterior descending (LAD) dissection but an otherwise normal coronary anatomy. The lesion was treated with four everolimus eluting stents. Initially the patient made an unremarkable recovery until ventricular fibrillation arrest occurred on the following day. Unsynchronized cardioversion restored a normal sinus rhythm and repeat catheterization revealed new right coronary artery (RCA) dissection. A wire was passed distally, but it was unclear whether this was through the true or false lumen and no stents could be placed. However, improvement of distal RCA perfusion was noted on angiogram. Despite failure of interventional therapy the patient was therefore treated conservatively. Early operation after myocardial infarction has a significantly elevated risk of mortality and the initial dissection had occurred within 24 hours. This strategy proved successful as follow-up transthoracic echocardiography after four months demonstrated a preserved left ventricular ejection fraction of 55-60% without regional wall motion abnormalities. The patient remained asymptomatic from a cardiac point of view. PMID:20932332

  13. Recurrent post-partum coronary artery dissection.

    PubMed

    Rajab, Taufiek K; Khalpey, Zain; Kraemer, Bernhard; Resnic, Frederic S; Gallegos, Robert P

    2010-10-09

    Coronary artery dissection is a rare but well-described cause for myocardial infarction during the post-partum period. Dissection of multiple coronary arteries is even less frequent. Here we present a case of recurrent post-partum coronary artery dissections. This unusual presentation poses unique problems for management. A 35 year-old female, gravida 3 para 2, presented with myocardial infarction 9 weeks and 3 days post-partum. Cardiac catheterization demonstrated left anterior descending (LAD) dissection but an otherwise normal coronary anatomy. The lesion was treated with four everolimus eluting stents. Initially the patient made an unremarkable recovery until ventricular fibrillation arrest occurred on the following day. Unsynchronized cardioversion restored a normal sinus rhythm and repeat catheterization revealed new right coronary artery (RCA) dissection. A wire was passed distally, but it was unclear whether this was through the true or false lumen and no stents could be placed. However, improvement of distal RCA perfusion was noted on angiogram. Despite failure of interventional therapy the patient was therefore treated conservatively. Early operation after myocardial infarction has a significantly elevated risk of mortality and the initial dissection had occurred within 24 hours. This strategy proved successful as follow-up transthoracic echocardiography after four months demonstrated a preserved left ventricular ejection fraction of 55-60% without regional wall motion abnormalities. The patient remained asymptomatic from a cardiac point of view.

  14. Mechanisms of Post-Replication DNA Repair

    PubMed Central

    Gao, Yanzhe; Mutter-Rottmayer, Elizabeth; Zlatanou, Anastasia; Vaziri, Cyrus; Yang, Yang

    2017-01-01

    Accurate DNA replication is crucial for cell survival and the maintenance of genome stability. Cells have developed mechanisms to cope with the frequent genotoxic injuries that arise from both endogenous and environmental sources. Lesions encountered during DNA replication are often tolerated by post-replication repair mechanisms that prevent replication fork collapse and avert the formation of DNA double strand breaks. There are two predominant post-replication repair pathways, trans-lesion synthesis (TLS) and template switching (TS). TLS is a DNA damage-tolerant and low-fidelity mode of DNA synthesis that utilizes specialized ‘Y-family’ DNA polymerases to replicate damaged templates. TS, however, is an error-free ‘DNA damage avoidance’ mode of DNA synthesis that uses a newly synthesized sister chromatid as a template in lieu of the damaged parent strand. Both TLS and TS pathways are tightly controlled signaling cascades that integrate DNA synthesis with the overall DNA damage response and are thus crucial for genome stability. This review will cover the current knowledge of the primary mediators of post-replication repair and how they are regulated in the cell. PMID:28208741

  15. Post-production modification of industrial enzymes.

    PubMed

    Minten, Inge J; Abello, Nicolas; Schooneveld-Bergmans, Margot E F; van den Berg, Marco A

    2014-01-01

    Industry has an increasing interest in the use of enzymes as environmentally friendly, highly efficient, and specific bio-catalysts. Enzymes have primarily evolved to function in aqueous environments at ambient temperature and pressure. These conditions however do not always correspond with industrial processes or applications, and only a small portion of all known enzymes are therefore suitable for industrial use. Protein engineering can sometimes be applied to convey more desirable properties to enzymes, such as increased stability, but is limited to the 20 naturally occurring amino acids or homologs thereof. Using post-production modification, which has the potential to combine desirable properties from the enzyme and the conjugated compounds, enzymes can be modified with both natural and synthetic molecules. This offers access to a myriad of possibilities for tuning the properties of enzymes. At this moment, however, the effects of post-production modification cannot yet be reliably predicted. The increasing number of applications will improve this so that the potential of this technology can be fully exploited. This review will focus on post-production modification of enzymes and its use and opportunities in industry.

  16. Post Disaster Governance, Complexity and Network Theory

    PubMed Central

    Lassa, Jonatan A.

    2015-01-01

    This research aims to understand the organizational network typology of large­-scale disaster intervention in developing countries and to understand the complexity of post-­disaster intervention, through the use of network theory based on empirical data from post-­tsunami reconstruction in Aceh, Indonesia, during 2005/­2007. The findings suggest that the ‘ degrees of separation’ (or network diameter) between any two organizations in the field is 5, thus reflecting ‘small­ world’ realities and therefore making no significant difference with the real human networks, as found in previous experiments. There are also significant loops in the network reflecting the fact that some actors tend to not cooperate, which challenges post­ disaster coordination. The findings show the landscape of humanitarian actors is not randomly distributed. Many actors were connected to each other through certain hubs, while hundreds of actors make ‘scattered’ single ‘principal-­client’ links. The paper concludes that by understanding the distribution of degree, centrality, ‘degrees of separation’ and visualization of the network, authorities can improve their understanding of the realities of coordination, from macro to micro scales. PMID:26236562

  17. Does post septoplasty nasal packing reduce complications?

    PubMed

    Naghibzadeh, Bijan; Peyvandi, Ali Asghar; Naghibzadeh, Ghazal

    2011-01-01

    The main issues in nasal surgery are to stabilize the nose in the good position after surgery and preserve the cartilages and bones in the favorable situation and reduce the risk of deviation recurrence. Also it is necessary to avoid the synechia formation, nasal valve narrowing, hematoma and bleeding. Due to the above mentioned problems and in order to solve and minimize them nasal packing, nasal splint and nasal mold have been advised. Patients for whom the nasal packing used may faced to some problems like naso-pulmonary reflex, intractable pain, sleep disorder, post operation infection and very dangerous complication like toxic shock syndrome. We have two groups of patients and three surgeons (one of the surgeons used post operative nasal packing in his patients and the two others surgeons did not).Complications and morbidities were compared in these two groups. Comparing the two groups showed that the rate of complication and morbidities between these two groups were same and the differences were not valuable, except the pain and discomfort post operatively and at the time of its removal. Nasal packing has several risks for the patients while its effects are not studied. Septoplasty can be safely performed without postoperative nasal packing. Nasal packing had no main findings that compensated its usage. Septal suture is one of the procedures that can be used as alternative method to nasal packing. Therefore the nasal packing after septoplasty should be reserved for the patients with increased risk of bleeding.

  18. AGR-1 Post Irradiation Examination Final Report

    SciTech Connect

    Demkowicz, Paul Andrew

    2015-08-01

    The post-irradiation examination (PIE) of the Advanced Gas Reactor (AGR)-1 experiment was a multi-year, collaborative effort between Idaho National Laboratory (INL) and Oak Ridge National Laboratory (ORNL) to study the performance of UCO (uranium carbide, uranium oxide) tristructural isotropic (TRISO) coated particle fuel fabricated in the U.S. and irradiated at the Advanced Test Reactor at INL to a peak burnup of 19.6% fissions per initial metal atom. This work involved a broad array of experiments and analyses to evaluate the level of fission product retention by the fuel particles and compacts (both during irradiation and during post-irradiation heating tests to simulate reactor accident conditions), investigate the kernel and coating layer morphology evolution and the causes of coating failure, and explore the migration of fission products through the coating layers. The results have generally confirmed the excellent performance of the AGR-1 fuel, first indicated during the irradiation by the observation of zero TRISO coated particle failures out of 298,000 particles in the experiment. Overall release of fission products was determined by PIE to have been relatively low during the irradiation. A significant finding was the extremely low levels of cesium released through intact coatings. This was true both during the irradiation and during post-irradiation heating tests to temperatures as high as 1800°C. Post-irradiation safety test fuel performance was generally excellent. Silver release from the particles and compacts during irradiation was often very high. Extensive microanalysis of fuel particles was performed after irradiation and after high-temperature safety testing. The results of particle microanalysis indicate that the UCO fuel is effective at controlling the oxygen partial pressure within the particle and limiting kernel migration. Post-irradiation examination has provided the final body of data that speaks to the quality of the AGR-1 fuel, building

  19. Post pressure hyperemia in the rat.

    PubMed

    Capp, C L; Dorwart, W C; Elias, N T; Hillman, S R; Lancaster, S S; Nair, R C; Ngo, B T; Rendell, M S; Smith, D M

    2004-03-01

    In prior studies in man, we have demonstrated that pressure-induced hyperemia lasts for prolonged periods as compared to the short-term hyperemia created by proximal arterial occlusion. We have analyzed this phenomenon in our well-studied rat model of skin blood flow. Skin blood flow was measured using laser Doppler techniques in Wistar Kyoto rats at the back, a nutritively perfused site, and at the plantar surface of the paw, where arteriovenous anastomotic perfusion dominates. A customized pressure feedback control device was used to vary applied pressures. At the back, pressures in excess of 80 mmHg resulted in occlusion, whereas at the paw 150 mmHg was required. The peak hyperemic flow after release of pressure was comparable to that elicited by proximal arterial occlusion with a blood pressure cuff. However, the post pressure hyperemia peak descended to a plateau value, which was 50-100% greater than baseline and continued for up to 20 min while the peak following proximal arterial occlusion returned to baseline within 4 min. At the back, post pressure hyperemia reached a maximum after application of 100 mmHg pressure. The application of higher pressures than required for occlusion produced no greater hyperemic response. At the paw, maximum post pressure hyperemia occurred at 100 mmHg, although this pressure level was not totally occlusive. Higher pressures resulted in no greater hyperemia. At the back, 10 min of occlusion produced a maximal peak value whereas 1 min was sufficient at the paw. The application of pressure to a heated probe with subsequent release, produced a hyperemic response. Normalized to baseline blood flow, there was no difference between the hyperemic responses at basal skin temperature and at 44 degrees C. There is a prolonged hyperemic response following local pressure occlusion compared to a much shorter period following proximal ischemic occlusion. One can presume two different mechanisms, one related to ischemia and the other a

  20. Comparison of two techniques for removing fiber posts.

    PubMed

    Gesi, A; Magnolfi, S; Goracci, C; Ferrari, M

    2003-09-01

    The purpose of this study was to evaluate the time needed to remove several types of fiber posts using two different bur kits. Estimates refer to the time needed to pass the fiber post until arriving at the gutta-percha. Sixty extracted anterior teeth were treated endodontically. A post space with a standard depth of 10 mm was prepared in each root canal. The sample was randomly divided into 3 groups of 20 specimens each. Three different types of posts were cemented: group 1, Conic 6% tapered fiber posts (Ghimas); group 2, FRC Poster fiber posts (Ivoclar-Vivadent); and group 3, Composipost carbon fiber posts (RTD). To remove the post, for half of each group's specimens the burs from the RTD fiber posts removal kit were used (subgroup A). From the other half of the teeth in each group (subgroup B), posts were removed by using a diamond bur and a Largo bur. Composipost carbon fiber posts (group 3) took significantly less time to remove than the other two types of posts (p < 0.05). For the bur kits, the procedure involving the use of a diamond and a Largo bur (subgroup B) was significantly faster (p < 0.05). The interaction between the type of post and the type of bur kit used was not significant (p > 0.05).

  1. Post-Polio Health International including International Ventilator Users Network

    MedlinePlus

    ... PHI Annual Reports Contact Us Copyright EDUCATION Post-Polio Health newsletter Health Care Considerations Handbook on the Late Effects ... Late Effects of Polio Post-Polio Syndrome (PPS) About Acute Polio Major ...

  2. 2. FULL VIEW OF BRIDGE, SHOWING INCLINED END POST (HATTER ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. FULL VIEW OF BRIDGE, SHOWING INCLINED END POST (HATTER POST), PORTAL BRACING, AND PORTAL STRUT AT EAST PORTAL, LOOKING WEST - Chester Bridge, Spanning Rock River on Old Marsh Road, East Waupun, Dodge County, WI

  3. 9. Detail of end post connection on south web, showing ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    9. Detail of end post connection on south web, showing vertical, end posts, pin and pin plate. View to south. - Slough Creek Bridge, Spanning Slough Creek at CART Road 330, Arrow Rock, Saline County, MO

  4. 1. PANORAMA, FROM ULAKTA HEAD COMMAND POST TO THE WEST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. PANORAMA, FROM ULAKTA HEAD COMMAND POST TO THE WEST TOWARD MOUNT BALLYHOO - Naval Operating Base Dutch Harbor & Fort Mears, Ulakta Head Fixed Defense Battery Command Post No. 1, Unalaska, Aleutian Islands, AK

  5. 1. PANORAMA, SHOWING COMMAND POST RELATION TO DUTCH HARBOR AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. PANORAMA, SHOWING COMMAND POST RELATION TO DUTCH HARBOR AND UNALASKA FROM THE TOP OF LITTLE SOUTH AMERICA - Naval Operating Base Dutch Harbor & Fort Mears, Hill 400 Fixed Defense Battery Command Post, Unalaska, Aleutian Islands, AK

  6. PANORAMA, FROM ULAKTA HEAD COMMAND POST TO THE WEST TOWARDS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    PANORAMA, FROM ULAKTA HEAD COMMAND POST TO THE WEST TOWARDS MOUNT BALLYHOO - Naval Operating Base Dutch Harbor & Fort Mears, Ulakta Head Fixed Defense Battery Command Post No. 1, Unalaska, Aleutian Islands, AK

  7. PANORAMA, SHOWING COMMAND POST RELATION TO DUTCH HARBOR AND UNALASKA ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    PANORAMA, SHOWING COMMAND POST RELATION TO DUTCH HARBOR AND UNALASKA FROM THE TOP OF LITTLE SOUTH AMERICA - Naval Operating Base Dutch Harbor & Fort Mears, Hill 400 Fixed Defense Battery Command Post, Unalaska, Aleutian Islands, AK

  8. Fitness, Not Fat, Is Key to Post-Stroke Recovery

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_164476.html Fitness, Not Fat, Is Key to Post-Stroke Recovery ... tied to post-stroke disability, the study found. Fitness was key, though. "Being physically inactive before stroke ...

  9. 25. Detail of cast iron lamp post base with fluted ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    25. Detail of cast iron lamp post base with fluted wooded post at top, located at north end of bridge. VIEW NORTHEAST - Chelsea Street Bridge & Draw Tender's House, Spanning Chelsea River, Boston, Suffolk County, MA

  10. 47 CFR 73.1230 - Posting of station license.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... principal control point of the transmitter. (b) Posting of the station license and any other instruments of... station license and any other instrument of station authorization shall be posted in a conspicuous...

  11. 31. BUILDING NO. 305, POST ENGINEERING STOREHOUSE, LOOKING AT NORTHEAST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    31. BUILDING NO. 305, POST ENGINEERING STOREHOUSE, LOOKING AT NORTHEAST CORNER. BUILDING NO. 301-A, POST ENGINWEERING STOREHOUSE, OIL HOUSE, IN BACKGROUND RIGHT. - Picatinny Arsenal, State Route 15 near I-80, Dover, Morris County, NJ

  12. Evaluation of Different Post Lengths’ Effect on Fracture Resistance of a Glass Fiber Post System

    PubMed Central

    Adanir, Necdet; Belli, Sema

    2008-01-01

    Objectives The purpose of this in vitro study was to evaluate the influence of different post lengths upon root fracture resistance. Methods 78 maxillary central teeth with similar dimensions were mounted in acrylic blocks with artificial silicone periodontal ligaments. Combinations of post lengths of 6 mm (shorter than 1/1 clinical crown length), 9 mm (1/1 clinical crown length), and 12 mm (longer than 1/1 clinical crown length) made up 6 different groups consisting of 13 teeth each. The glass fiber posts (Snowpost) were cemented with Super-Bond C&B and Panavia F luting cement. Composite-resin cores were made with Clearfil PhotoCore. The specimens were tested in a universal test machine. The testing machine applied controlled loads to the core, 2 mm from its incisal edge, on the palatal side at an angle 135 degrees to the long axis of the root. The testing machine was set at a crosshead speed of 5mm per minute. All samples were loaded until failure. Results There was no statistically significant difference between cements (P>.05). Posts shorter than clinical crown length, demonstrated root fracture under significantly lower loading forces (P<.05). Conclusion Usage of posts shorter than clinical crowns should be avoided to eliminate clinical failure. PMID:19212505

  13. Fatigue resistance of teeth restored with fiber posts and different post cementation strengths.

    PubMed

    Valandro, Luiz Felipe; Zardin, Lucas Wadas; de Villa, Marco Antonio; Amaral, Marina; Galhano, Graziela; Baldissara, Paolo; Bottino, Marco Antonio

    2009-01-01

    This study sought to evaluate how different post cementation strategies affected the fatigue resistance of bovine teeth restored with glass fiber posts. The canals of 63 single-rooted bovine teeth (each 16 mm in length) were prepared to 9 mm using a preparation drill from a double-tapered fiber post system. Each specimen was embedded in a PVC cylinder using acrylic resin up to 3 mm of the most coronal portion of the specimen and was allocated into one of seven groups (n = 9) based on the strategies for cementation. After cementation, a standard core build-up was made with composite resin. The specimens were stored for seven days and submitted to mechanical cycling (50 N, 8 Hz, 37 degrees C). After fatigue testing, a score was given to each specimen, based on the number of fatigue cycles required to fracture the specimens; the scores were submitted to statistic analysis (Kruskal-Wallis, alpha = 0.05). The strategy for post cementation did not affect the resistance to fatigue (P = 0.8669). Based on the results, the resistance to fatigue does not appear to depend on the post cementation strategy.

  14. 29 CFR 22.36 - Post-hearing briefs.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 1 2014-07-01 2013-07-01 true Post-hearing briefs. 22.36 Section 22.36 Labor Office of the Secretary of Labor PROGRAM FRAUD CIVIL REMEDIES ACT OF 1986 § 22.36 Post-hearing briefs. The ALJ may require the parties to file post-hearing briefs. In any event, any party may file a post-hearing brief....

  15. 22 CFR 224.36 - Post-hearing briefs.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Post-hearing briefs. 224.36 Section 224.36 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT IMPLEMENTATION OF THE PROGRAM FRAUD CIVIL REMEDIES ACT § 224.36 Post-hearing briefs. The ALJ may require the parties to file post-hearing briefs. In...

  16. 38 CFR 13.110 - Escheat; post fund.

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    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Escheat; post fund. 13... BENEFITS ADMINISTRATION, FIDUCIARY ACTIVITIES § 13.110 Escheat; post fund. (a) Escheat; 38 U.S.C. 5502(e... necessary to determine that an escheat is in order. (b) General Post Fund; 38 U.S.C. 5220(a). Upon the...

  17. 77 FR 42342 - Post Office Box Service Enhancements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-18

    ... Post Office Box Service Enhancements AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The... certain competitive post office box locations. This notice addresses procedural steps associated with the... introduction of enhanced services that it offers to post office box customers at certain retail...

  18. 77 FR 36585 - Post Office Box Service Enhancements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-19

    ... COMMISSION Post Office Box Service Enhancements AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY... concerning enhanced services for Post Office Box service. It also addresses the status of a related Complaint... enhanced services that it offers to post office box customers at certain retail locations.\\1\\ The...

  19. 5 CFR 1304.4605 - Post-employment restrictions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 3 2012-01-01 2012-01-01 false Post-employment restrictions. 1304.4605 Section 1304.4605 Administrative Personnel OFFICE OF MANAGEMENT AND BUDGET ADMINISTRATIVE PROCEDURES POST EMPLOYMENT CONFLICT OF INTEREST § 1304.4605 Post-employment restrictions. (a) General Restrictions...

  20. 5 CFR 1304.4605 - Post-employment restrictions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 3 2013-01-01 2013-01-01 false Post-employment restrictions. 1304.4605 Section 1304.4605 Administrative Personnel OFFICE OF MANAGEMENT AND BUDGET ADMINISTRATIVE PROCEDURES POST EMPLOYMENT CONFLICT OF INTEREST § 1304.4605 Post-employment restrictions. (a) General Restrictions...