The use of backward stepwise multiple correlations highlighted the interaction between several body parameters and their relation to standing stability in both able-bodied girls and scoliotic subjects. The scoliotic group displayed a much larger number of correlations between standing stability and body posture parameters than the nonscoliotic group. Standing imbalance was related to altered body posture parameters measured in the frontal and horizontal planes only. Although the correlation coefficients were relatively high, factors other than body posture parameters appeared related to standing imbalance in adolescent idiopathic scoliosis. These findings support the concept of either a primary or a secondary dysfunction in the postural regulation system of scoliotic subjects.
Summary:We report a series of 37 consecutive patients with multiple myeloma (MM) who received an allograft between 1990 and 2000 at our institution. Median age was 47 years, and nearly 70% of patients were Durie-Salmon stage III. A median of five cycles of chemotherapy were given before transplant, with a median interval between diagnosis and transplant of 9.3 months. We report a nonrelapse mortality rate of 22% with a median followup period of 40 months, whereas complete remission (CR) rate at 12 months is estimated at 57%. Treatment failure rate and overall survival at 40 months are estimated at 52% and 32%, respectively. The number of chemotherapy cycles prior to allotransplantation achieved borderline statistical significance as a poor prognosis factor for overall survival (P ؍ 0.05), while the presence of chronic graft-versus-host disease (cGVHD) was significantly correlated with CR achievement (P ؍ 0.036). Our study confirms that early allografting in MM can yield toxicity rates significantly lower than those associated with historical cohorts, and supports the hypothesis that cumulative chemotoxicity has a negative influence on mortality and survival rates. More importantly, our study clearly demonstrates an association between cGVHD and CR and brings further evidence in favor of a graft-versus-myeloma effect. Bone Marrow Transplantation (2001) 28, 841-848.
IntroductionIn all animals with an adaptive immune system, the thymus is the primary lymphoid organ for T-cell development and no other organ can compensate for defective thymic function. 1 This is problematic considering that progressive thymus atrophy ultimately affects all aging subjects and can even impinge on younger subjects affected by several serious illnesses. [2][3][4] A key question that has baffled immunologists for 40 years is the nature of the signals provided by thymic stromal cells that are necessary and sufficient for T-cell development. 5 Strikingly, recent studies have shown that a bone marrow stromal cell line ectopically expressing the Notch ligand Deltalike-1 (OP9-DL1) acquired the capacity to induce the differentiation of hematopoietic progenitors into functional T cells in vitro. 6,7 A startling and important implication is that the 3-dimensional thymic microenvironment and the presence of thymic epithelial cells are not essential for T-cell development. 6 Thymusindependent T-cell development can also take place in vivo. [8][9][10] Thus, using transgenic mice bearing a green fluorescent protein (GFP) gene placed under the control of the recombinationactivating gene 2 (RAG2) promoter, Guy-Grand et al 9 showed that T lymphopoiesis occurred in lymph nodes (LNs) and less in the Peyer patches of athymic mice. This cryptic T-cell development pathway however generates only limited numbers of mature T cells. 9 Unexpectedly, signals transmitted by the leukemia inhibitory factor (LIF) receptor following prolonged exposure to mouse LIF or bovine oncostatin M (OM) amplify the cryptic LN Tlymphopoietic pathway and transform the mouse LNs into primary T-lymphoid organs. [11][12][13][14][15][16] Thus, about 215 ϫ 10 6 Thy1 ϩ CD4 ϩ CD8 ϩ cells are present in the mesenteric LNs of 12-week-old lckOM transgenic mice that express the OM transgene under the control of the proximal lymphocyte protein tyrosine kinase (lck) promoter. 15 Studies of OM-transgenic mice showed that this extrathymic pathway is thymus independent, generates functional T lymphocytes, and is regulated by a cyclooxygenase-2-dependent proliferation of high endothelial venules. [16][17][18][19] The goal of our work was to determine why LNs are normally unable to support T-cell development and how OM can alleviate this defect. We surmised that such knowledge would provide invaluable information on the essence of a primary T-lymphoid organ, that is, how stromal cells regulate crucial early steps in T-cell development. Materials and methods MiceC57BL/6J (B6) mice were purchased from The Jackson laboratory (Bar Harbor, ME). LckOM transgenic mice on a C57BL/6J background have been previously described. 14,15 From Flow cytometry analysis and cell sortingThe following antibodies were used: biotin and phycoerythrin-cyanin 7 (PE-Cy7) anti-CD8␣ (53-6.7); biotin anti-CD8 (53-5.8); allophycocyanin (APC)-Cy7 anti-CD4; biotin anti-NK1.1 (PK136); biotin, APC, and fluorescein isothiocyanate (FITC) anti-T-cell receptor  (anti-TCR; H57); biotin anti-TCR...
Incidence of grade II-IV acute graft-versus-host disease (aGVHD) in nonmyeloablative (NMA) transplant recipients remains high. To date, the ideal prophylaxis regimen, which minimizes aGVHD and chronic GVHD (cGVHD), but does not abrogate graft-versus-tumor (GVT) response, has not been described. Because tacrolimus is more potent than cyclosporine (CSA), and because mycophenolate mofetil (MMF) is an effective immunosuppressant that does not lead to mucositis, we hypothesized that a combination of these 2 oral agents may be an effective GVHD prophylactic strategy. We, therefore, designed an outpatient prospective cohort study with a conditioning regimen consisting of fludarabine (Flu) 30 mg/m2 daily and cyclophosphamide (Cy) 300 mg/m2 daily for 5 days followed by infusion of blood stem cells. Tacrolimus 3mg twice a day was started on day (D) -8, adjusted to achieve levels 10-15 nmol/L, continued until D +50 and then tapered by D +100 or +180 according to estimated risk of relapse. MMF 1000 mg twice a day was started on D +1 and discontinued on D +50. To date, 131 patients (males/females: 75/56) with a median age of 54 years have received a 6/6 matched sibling transplant using this protocol. Indication for NMA transplant included age >55 years (24%), expected increased risk of toxicity (28%), or participation in a multiple myeloma (MM) sequential protocol (48%). Most common diagnoses included MM (N = 62), non-Hodgkin lymphoma (NHL, N = 46), and acute leukemia (N = 10). Following infusion of 6.8 x 10(6) CD34+ cells/kg (range: 0.30-22.3), neutrophil and lymphocyte engraftment occurred in 95% of patients by D +180. The estimated cumulative incidence of classical grade I-IV aGVHD by D +120 was 11.6% (95% confidence interval [CI]: 7.1-18.5). No grade IV aGVHD was observed. In addition, 15 patients (12%: CI: 7.4-19.2; median D +140) developed an overlap syndrome consisting of clinical and histologic features of both aGVHD and cGVHD simultaneously. The estimated cumulative incidence of extensive cGVHD was 76.1% (95% CI: 67.4-83.9) at 2 years, with clinical features at presentation similar to other reported series. In patients developing extensive cGVHD, the probability of remaining on immunosuppression at 5 years was 34.8% (95% CI: 16.4-57.3). With a median follow-up of 982 days, the estimated probabilities of nonrelapse mortality (NRM) and overall survival (OS) were 15.5% (95% CI: 9.0-26.1) and 62.7% (95% CI: 51.4-72.1). The cumulative incidence of relapse was 30% at 7 years. Following NMA transplant, disease-free survival (DFS) was highest in recipients with follicular NHL (79.8%: 95% CI: 57.6-91.2) and lowest in large cell NHLs (34.3%: 95% CI: 1.6-75.9). From this large group of patients treated with a uniform conditioning and GVHD prophylaxis regimen, we conclude that aGVHD prophylaxis with early use of tacrolimus and MMF is safe, effective, and associated with low NRM. Future strategies will need to focus on decreasing the incidence of extensive cGVHD without increasing the risk of relapse.
A 19-year-old woman presented with a primary mediastinal B-cell lymphoma invading the superior vena cava with associated thrombosis of the left brachiocephalic and subclavian vein. She underwent thrombolysis followed by chemotherapy. The midtreatment 18F-FDG PET/CT demonstrated important regression of the primary mediastinal B-cell lymphoma, but showed intense focal hepatic uptake in segment IV, without a corresponding lesion on ultrasonography, non–contrast-enhanced low-dose CT, and MRI. This focal uptake disappeared on a subsequent 18F-FDG PET/CT study when the radiotracer was injected in the foot, suggesting an anomalous venous return pathway that persisted despite thrombolysis.
Fisher succeeded early on in redefining Student's t-distribution in geometrical terms on a central hypersphere. Intriguingly, a noncentral analytical extension for this fundamental Fisher-Student's central hypersphere h-distribution does not exist. We therefore set to derive the noncentral h-distribution and use it to graphically illustrate the limitations of the Neyman-Pearson null hypothesis significance testing framework and the strengths of the Bayesian statistical hypothesis analysis framework on the hypersphere polar axis, a compact nontrivial one-dimensional parameter space. Using a geometrically meaningful maximal entropy prior, we requalify the apparent failure of an important psychological science reproducibility project. We proceed to show that the Bayes factor appropriately models the two-sample t-test p-value density of a gene expression profile produced by the high-throughput genomic-scale microarray technology, and provides a simple expression for a local false discovery rate addressing the multiple hypothesis testing problem brought about by such a technology.
Background: Erythrocytosis is a frequent request for consultation in the hematologic field. The diagnostic approach is well established in the general population but in a young adult, finding the etiology of erythrocytosis can be a real diagnostic challenge. Methods: This is an observational retrospective unicentric study made at the Sherbrooke University Hospital Center, over a period of 20 years (1995-2015). Every patient aged between 16 and 35 years old with a significant elevation of hemoglobin or hematocrit was included (hemoglobin > 185 g/L and/or hematocrit > 0.52 in men; hemoglobin > 165 g/L and/or hematocrit > 0.48 in women). Results: Totally, 426 patients met the inclusion criteria (over a total of 113,453 complete blood counts) but only 56 entered the study for investigations. The majority of patients were of male gender, 43% of the patients were obese, 59% were smokers and 38% used excess alcohol or recreational drugs. Twenty-five patients had the diagnosis of absolute erythrocytosis. Seven patients had the diagnosis of relative erythrocytosis and no cause could be identified in 24 patients. No primary erythrocytosis was found in this cohort. Among the 25 patients with secondary erythrocytosis, hypoxia was the most frequent etiology identified. Less than half of the patients in the cohort had long term follow-up. Search for JAK2 mutation and serum EPO dosage were performed in 17.9% and 23.2% of cases respectively. Seven patients were treated with aspirin and five patients had phlebotomies. Conclusions: This retrospective study reveals an actual clinical management that is often discordant with the current recommendations and a frequent lack of follow-up after initial investigations. Harmonization of management of erythrocytosis appears to be highly desirable.
The univariate noncentral distributions can be derived by multiplying their central distributions with translation factors. When constructed in terms of translated uniform distributions on unit radius hyperspheres, these translation factors become generating functions for classical families of orthogonal polynomials. The ultraspherical noncentral t, normal N, F, and χ2 distributions are thus found to be associated with the Gegenbauer, Hermite, Jacobi, and Laguerre polynomial families, respectively, with the corresponding central distributions standing for the polynomial family-defining weights. Obtained through an unconstrained minimization of the Gibbs potential, Jaynes’ maximal entropy priors are formally expressed in terms of the empirical densities’ entropic convex duals. Expanding these duals on orthogonal polynomial bases allows for the expedient determination of the Jaynes–Gibbs priors. Invoking the moment problem and the duality principle, modelization can be reduced to the direct determination of the prior moments in parametric space in terms of the Bayes factor’s orthogonal polynomial expansion coefficients in random variable space. Genomics and geophysics examples are provided.
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