Treatment with interferon prolongs survival in chronic myelogenous leukemia. We conducted a clinical trial to assess the efficacy of treatment with a combination of interferon and cytarabine.
...Previously untreated patients with chronic myelogenous leukemia were randomly assigned to receive either hydroxyurea (50 mg per kilogram of body weight per day) and interferon alfa-2b (5 million units per square meter of body-surface area per day), or hydroxyurea and interferon in the same dosages plus monthly courses of cytarabine (20 mg per square meter per day, for 10 days). The end points were overall survival, complete hematologic remission at 6 months, and major cytogenetic response (less than 35 percent Philadelphia chromosome-positive cells in the bone marrow) at 12 months.
The trial was stopped when a sequential analysis showed a benefit of interferon and cytarabine. A significant improvement in survival was observed in the interferon-cytarabine group (360 patients) as compared with the interferon group (361 patients) (P=0.02; relative risk of death, 0.64; 95 percent confidence interval, 0.44 to 0.93). After three years, the survival rate was 85.7 percent with interferon and cytarabine and 79.1 percent with interferon alone. The rate of hematologic response was higher in the interferon-cytarabine group than in the interferon group (P=0.003). Major cytogenetic responses were observed 12 months after randomization in 126 of 311 patients treated with interferon and cytarabine (41 percent) and in 75 of 314 patients treated with interferon only (24 percent, P<0.001).
The combination of interferon and cytarabine, as compared with interferon alone, increases the rate of major cytogenetic response and prolongs survival in patients with the chronic phase of chronic myelogenous leukemia.
Référentiel, réflexif, métaphorique constituent un échantillon des expressions et concepts employés pour qualifier les films de Tim Burton, attestant du lien qui unit ce corpus à l’histoire de son ...art et à son époque. Partant de ce constat, cet ouvrage formule l’hypothèse que cette filmographie constitue un cinéma de la ré-imagination – le cinéaste utilise d’ailleurs lui même ce terme pour définir l’approche conceptuelle de son cinéma. Ses films, conçus comme des boîtes à jouets rassemblant souvenirs, imagination et pièces intactes, mettent en scène ces différents éléments en tant que base formelle des ré imaginations burtoniennes. Ils s’entremêlent au sein d’une même image, tout au long d’un fil narratif parfois ténu. En adoptant des procédés cinématographiques et filmiques ramenant vers des âges antérieurs du septième art et rattachant les intrigues au domaine de l’imaginaire par l’intermédiaire de manifestations mentales, Tim Burton construit un cinéma ancré dans le passé qui aspire à reconstituer le royaume de l’enfance. Cette étude justifie d’abord le choix de ce terme en regard des concepts préexistants pour ensuite analyser ce qu’il englobe et implique de singulier dans la filmographie de Tim Burton.
BACKGROUND
In experimental canine septic shock, depressed circulating granulocyte counts were associated with a poor outcome and increasing counts with prophylactic granulocyte colony‐stimulating ...factor (G‐CSF) improved outcome. Therapeutic G‐CSF, in contrast, did not improve circulating counts or outcome, and therefore investigation was undertaken to determine whether transfusing granulocytes therapeutically would improve outcome.
STUDY DESIGN AND METHODS
Twenty‐eight purpose‐bred beagles underwent an intrabronchial Staphylococcus aureus challenge and 4 hours later were randomly assigned to granulocyte (40‐100 × 109 cells) or plasma transfusion.
RESULTS
Granulocyte transfusion significantly expanded the low circulating counts for hours compared to septic controls but was not associated with significant mortality benefit (1/14, 7% vs. 2/14, 14%, respectively; p = 0.29). Septic animals with higher granulocyte count at 4 hours (median interquartile range of 3.81 3.39‐5.05 vs. 1.77 1.25‐2.50) had significantly increased survival independent of whether they were transfused with granulocytes. In a subgroup analysis, animals with higher circulating granulocyte counts receiving donor granulocytes had worsened lung injury compared to septic controls. Conversely, donor granulocytes decreased lung injury in septic animals with lower counts.
CONCLUSION
During bacterial pneumonia, circulating counts predict the outcome of transfusing granulocytes. With low but normal counts, transfusing granulocytes does not improve survival and injures the lung, whereas for animals with very low counts, but not absolute neutropenia, granulocyte transfusion improves lung function.
Objective: We assessed sustainability of an empirically supported, transdiagnostic youth psychotherapy program when therapist supervision was shifted from external experts to internal clinic staff. ...Method: One hundred sixty-eight youths, aged 6-15 years, 59.5% male, 85.1% Caucasian, were treated for anxiety, depression, traumatic stress, or conduct problems by clinicians employed in community mental health clinics. In Phase 1 (2.7 years), 1 group of clinicians, the Sustain group, received training in Child STEPs (a modular transdiagnostic treatment + weekly feedback on youth response) and treated clinic-referred youths, guided by weekly supervision from external STEPs experts. In Phase 2 (2.9 years), Sustain clinicians treated additional youths but with supervision by clinic staff who had been trained to supervise STEPs. Also in Phase 2, a new group, External Supervision clinicians, received training and supervision from external STEPs experts and treated referred youths. Phase 2 youths were randomized to Sustain or External Supervision clinicians. Groups were compared on 3 therapist fidelity measures and 14 clinical outcome measures. Results: Sustain clinicians maintained their previous levels of fidelity and youth outcomes after switching from external to internal supervision; and in Phase 2, the Sustain and External Supervision groups also did not differ on fidelity or youth outcomes. Whereas all 34 group comparisons were nonsignificant, trends with the largest effect sizes showed better clinical outcomes for internal than external supervision. Conclusions: Implementation of empirically supported transdiagnostic treatment may be sustained when supervision is transferred from external experts to trained clinic staff, potentially enhancing cost-effectiveness and staying power in clinical practice.
What is the public health significance of this article?
The study suggests that clinical service programs for youths may be able to sustain the implementation of an empirically supported transdiagnostic treatment without unending dependence on external expert supervision from the treatment developer team. Internal clinic staff were trained to supervise a specific empirically supported transdiagnostic treatment; the clinicians they supervised achieved treatment fidelity and youth clinical outcomes that did not differ significantly from those of clinicians supervised by external experts.
The contribution of neuronal dysfunction to neurodegeneration is studied in a mouse model of spinocerebellar ataxia type 1 (SCA1) displaying impaired motor performance ahead of loss or atrophy of ...cerebellar Purkinje cells. Presymptomatic SCA1 mice show a reduction in the firing rate of Purkinje cells (both in vivo and in slices) associated with a reduction in the efficiency of the main glutamatergic synapse onto Purkinje cells and with increased A-type potassium current. The A-type potassium channel Kv4.3 appears to be internalized in response to glutamatergic stimulation in Purkinje cells and accumulates in presymptomatic SCA1 mice. SCA1 mice are treated with aminopyridines, acting as potassium channel blockers to test whether the treatment could improve neuronal dysfunction, motor behavior, and neurodegeneration. In acutely treated young SCA1 mice, aminopyridines normalize the firing rate of Purkinje cells and the motor behavior of the animals. In chronically treated old SCA1 mice, 3,4-diaminopyridine improves the firing rate of Purkinje cells, the motor behavior of the animals, and partially protects against cell atrophy. Chronic treatment with 3,4-diaminopyridine is associated with increased cerebellar levels of BDNF, suggesting that partial protection against atrophy of Purkinje cells is possibly provided by an increased production of growth factors secondary to the reincrease in electrical activity. Our data suggest that aminopyridines might have symptomatic and/or neuroprotective beneficial effects in SCA1, that reduction in the firing rate of Purkinje cells can cause cerebellar ataxia, and that treatment of early neuronal dysfunction is relevant in neurodegenerative disorders such as SCA1.
A number of trace metals play essential roles in marine ecosystem structure and biological productivity. Until recently, it has been argued that phytoplankton access primarily dissolved iron, while ...particulate iron was considered a refractory material with little use biologically and limited interaction with the dissolved pool. In order to assess the transfer mechanisms between sediment-sourced particulate trace metals and the dissolved pool, we conducted a 14-month incubation that reacted resuspended sediments with natural seawater, both originating from the Kerguelen area (KEOPS cruises; Southern Ocean), in the dark, and at concentrations replicating natural conditions. Three types of sediments were investigated (named BioSi, BioSi + Ca, and Basalt), mostly composed of (i) biogenic silica (bSiO2), (ii) bSiO2 and calcite, and (iii) basaltic fragments, respectively. The release of dissolved silicon (dSi), iron (dFe) and manganese (dMn) was monitored regularly throughout the incubation, as well as living bacteria density and Fe organic ligands. Depending on the origin and composition of the sediment, unique dFe and dMn fluxes were observed, including a strong decoupling between dFe and dMn. The basaltic sediment released up to 1.09 ± 0.04 nmol L−1 of dFe and 0.28 ± 0.09 nmol L−1 of dMn, while the biogenic sediments released a higher 3.91 ± 0.04 nmol L−1 and 8.03 ± 0.42 nmol L−1 of dFe and dMn, respectively. Several factors influencing the release and removal of dFe and dMn were discernable at the temporal sampling resolution of the incubation, including the structural composition of the sediment, bacterial abundance, and the formation of manganese oxides. The regular sampling over short timescales and the extended sampling over one year proved to be critical to constrain the processes and exchanges that govern the contribution of the particulate to the dissolved pools. Overall, this incubation provides a strong basis for reassessing the role of resuspended sedimentary particles in the marine biogeochemical cycles of Fe and Mn. Indeed, we show that biogenic silica, calcite-rich and basaltic particles can contribute substantial dissolved Fe and Mn to the overlying water column. In the future, the global extent of this previously overlooked external metal source should be quantified through further process studies and biogeochemical models.
This article is part of a special issue entitled: “Cycles of trace elements and isotopes in the ocean – GEOTRACES and beyond” - edited by Tim M. Conway, Tristan Horner, Yves Plancherel, and Aridane G. González.
•Resuspended sedimentary particles contribute to a substantial flux of trace metals into the overlying oceanic water column•The release of dissolved Fe and Mn from resuspended sedimentary particles is decoupled through time•Biogenic silica and basaltic-rich particles are substantial sources of dissolved Fe•Calcite-rich particles are substantial sources of dissolved Mn
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Provider: - Institution: - Data provided by Europeana Collections- Avec mode texte- Manuels d'enseignement primaire- All metadata published by Europeana are available free of restriction under the ...Creative Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
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