Jaynes-Gibbs Entropic Convex Duals and Orthogonal Polynomials.

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.

Focal Liver 18F-FDG Uptake in a Patient Who Underwent Thrombolysis for Brachiocephalic and Subclavian Thrombosis: A Potential Pitfall.

ABSTRACT: 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.

Graft-versus-host disease prophylaxis with tacrolimus and mycophenolate mofetil in HLA-matched nonmyeloablative transplant recipients is associated with very low incidence of GVHD and nonrelapse mortality.

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.

Retrospective Study of High Hemoglobin Levels in 56 Young Adults.

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.

T-cell generation by lymph node resident progenitor cells.

In the thymus, 2 types of Lin-Sca-1+ (lineage-negative stem cell antigen-1-positive) progenitors can generate T-lineage cells: c-Kit(hi) interleukin-7 receptor alpha-negative (c-Kit(hi)IL-7Ralpha-) and c-Kit(lo)IL-7Ralpha+. While c-Kit(hi)IL-7Ralpha- progenitors are absent, c-Kit(lo)IL-7Ralpha+ progenitors are abundant in the lymph nodes (LNs). c-Kit(lo)IL-7Ralpha+ progenitors undergo abortive T-cell commitment in the LNs and become arrested in the G1 phase of the cell cycle because they fail both to up-regulate c-myb, c-myc, and cyclin D2 and to repress junB, p16(INK4a), and p21(Cip1/WAF). As a result, development of LN c-Kit(lo)IL-7Ralpha+ progenitors is blocked at an intermediate CD44+CD25lo development stage in vivo, and LN-derived progenitors fail to generate mature T cells when cultured with OP9-DL1 stromal cells. LN stroma can provide key signals for T-cell development including IL-7, Kit ligand, and Delta-like-1 but lacks Wnt4 and Wnt7b transcripts. LN c-Kit(lo)IL-7Ralpha+ progenitors are able to generate mature T cells when cultured with stromal cells producing wingless-related MMTV integration site 4 (Wnt4) or upon in vivo exposure to oncostatin M whose signaling pathway intersects with Wnt. Thus, supplying Wnt signals to c-Kit(lo)IL-7Ralpha+ progenitors may be sufficient to transform the LN into a primary T-lymphoid organ. These data provide unique insights into the essence of a primary T-lymphoid organ and into how a cryptic extrathymic T-cell development pathway can be amplified.

Relations between standing stability and body posture parameters in adolescent idiopathic scoliosis.

STUDY DESIGN: A retrospective study of standing imbalance and body posture in 71 able-bodied girls and subjects with adolescent idiopathic scoliosis was conducted. OBJECTIVE: To test the hypothesis that postural parameters are related to standing stability parameters. SUMMARY OF BACKGROUND DATA: Spinal deformity not only modifies the shape of the trunk, but also changes the relations between body segments affecting posture in scoliotic children. These postural adaptations to the scoliotic curve progression could be linked in part to increased body sway in upright standing. This has not yet been related to specific postural parameters involving the head, trunk, and pelvis in nontreated idiopathic scoliosis. METHODS: The head, trunk, and pelvis orientations of each subject were measured by a Flock of Bird system. An AMTI force platform was used to assess quiet standing stability and to monitor the position and displacement of the center of pressure (COP). The center of mass (COM) excursion was estimated from a biomechanical model using force plate information only. Analyses of variance (ANOVAS) were performed to determine the statistical differences between the scoliotic and nonscoliotic subjects, and backward stepwise multiple regression analyses were performed to identify any correlation between measures of quiet standing stability and body postural parameters RESULTS: The scoliotic group was characterized by a decrease in standing stability. There was an increase in the sway areas measured by the variations of the COP and COM. From the backward stepwise multiple regression analysis, it appears that for the able-bodied girls, the body posture parameters were correlated only with the mean anteroposterior center of pressure (COP(AP)) position. For the scoliotic group, the sway areas and the mean position of the centers of pressure and the COP(AP)-COM(AP) were correlated significantly with body posture parameters. The higher COP-COM differences for the scoliotic group were attributed to a greater neuromuscular demand to maintain standing balance. The coefficients of correlation of the multiple regression analyses ranged from 0.64 to 0.85 for the nonscoliotic group and from 0.55 to 0.72 for the scoliotic group. CONCLUSIONS: 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.