Rituximab monitoring and redosing in pediatric neuromyelitis optica spectrum disorder.

Abstract OBJECTIVE: To study rituximab in pediatric neuromyelitis optica (NMO)/NMO spectrum disorders (NMOSD) and the relationship between rituximab, B cell repopulation, and relapses in order to improve rituximab monitoring and redosing. METHODS: Multicenter retrospective study of 16 children with NMO/NMOSD receiving 652 rituximab courses. According to CD19 counts, events during rituximab were categorized as "repopulation," "depletion," or "depletion failure" relapses (repopulation threshold CD19 6510 7 10(6) cells/L). RESULTS: The 16 patients (14 girls; mean age 9.6 years, range 1.8-15.3) had a mean of 6.1 events (range 1-11) during a mean follow-up of 6.1 years (range 1.6-13.6) and received a total of 76 rituximab courses (mean 4.7, range 2-9) in 42.6-year cohort treatment. Before rituximab, 62.5% had received azathioprine, mycophenolate mofetil, or cyclophosphamide. Mean time from rituximab to last documented B cell depletion and first repopulation was 4.5 and 6.8 months, respectively, with large interpatient variability. Earliest repopulations occurred with the lowest doses. Significant reduction between pre- and post-rituximab annualized relapse rate (ARR) was observed (p = 0.003). During rituximab, 6 patients were relapse-free, although 21 relapses occurred in 10 patients, including 13 "repopulation," 3 "depletion," and 4 "depletion failure" relapses. Of the 13 "repopulation" relapses, 4 had CD19 10-50 7 10(6) cells/L, 10 had inadequate monitoring ( 641 CD19 in the 4 months before relapses), and 5 had delayed redosing after repopulation detection. CONCLUSION: Rituximab is effective in relapse prevention, but B cell repopulation creates a risk of relapse. Redosing before B cell repopulation could reduce the relapse risk further. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that rituximab significantly reduces ARR in pediatric NMO/NMOSD. This study also demonstrates a relationship between B cell repopulation and relapses

Extremely red radio galaxies

At least half the radio galaxies at z>1 in the 7C Redshift Survey have extremely red colours (R-K>5), consistent with stellar populations which formed at high redshift (z>5). We discuss the implications of this for the evolution of massive galaxies in general and for the fraction of near-IR-selected EROs which host AGN, a result which is now being tested by deep, hard X-ray surveys. The conclusion is that many massive galaxies undergo at least two active phases: one at z~5 when the black hole and stellar bulge formed and another at z~1-2 when activity is triggered by an event such as an interaction or merger.Comment: 6 pages, 2 figures, to appear in the proceedings of the workshop on "QSO hosts and their environments", IAA, Granada, 10-12 Jan 2001, Ed. I. Marque

Affirmative Action Programs in Social Service Agencies: Status of the Female M.S.W.

Job status and salary inequities between men and women have only recently been documented (Kravetz 1976). The federal government, over the past few decades, through various acts and executive orders, has created legislation to prohibit discrimination based on race, sex, color, religion or national origin in all employment practices. The question is to what extent this legislation has permeated social service agencies and affected their employment patterns, particularly with respect to administrative positions. In 1976, the Women\u27s Issues Committee of the Oregon Chapter of the National Association of Social Workers (NASW), addressed this question by initiating a study of social work employment in Oregon. The first part of the study examined the salaries and positions of NASW members in this state. The second part of the study was designed to study more specifically the employment patterns of women MSWs in Oregon\u27s social service agencies. Under the auspices of the Women\u27s Issues Committee, the second part of the study was designed and conducted by eight graduate students at the School of Social Work at Portland State University. One objective of the study was to find out the proportion of men and women filling the management positions in local social service agencies. But the primary purpose of the study was to examine the management-executive employment patterns in agencies before and after affirmative action programs were instituted. An attempt was then made to determine the effects, if any, of such programs. It was hoped that the results would clarify how agencies implement their affirmative action programs, the effects of implementation, and the barriers to the employment of women in management positions

Essential role of CFTR in PKA-dependent phosphorylation, alkalinization, and hyperpolarization during human dperm capacitation

Mammalian sperm require to spend a limited period of time in the female reproductive tract to become competent to fertilize in a process called capacitation. It is well established that HCO3 − is essential for capacitation because it activates the atypical soluble adenylate cyclase ADCY10 leading to cAMP production, and promotes alkalinization of cytoplasm, and membrane hyperpolarization. However, how HCO3 − is transported into the sperm is not well understood. There is evidence that CFTR activity is involved in the human sperm capacitation but how this channel is integrated in the complex signaling cascades associated with this process remains largely unknown. In the present work, we have analyzed the extent to which CFTR regulates different events in human sperm capacitation. We observed that inhibition of CFTR affects HCO3 −-entrance dependent events resulting in lower PKA activity. CFTR inhibition also affected cAMP/PKA-downstream events such as the increase in tyrosine phosphorylation, hyperactivated motility, and acrosome reaction. In addition, we demonstrated for the first time, that CFTR and PKA activity are essential for the regulation of intracellular pH, and membrane potential in human sperm. Addition of permeable cAMP partially recovered all the PKA-dependent events altered in the presence of inh-172 which is consistent with a role of CFTR upstream of PKA activation.Fil: Puga Molina, Lis del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Pinto, Nicolás Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Torres Rodríguez, Paulina. Universidad Nacional Autónoma de México; MéxicoFil: Romarowski, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Vicens Sanchez, Alberto. Universidad Nacional Autónoma de México; MéxicoFil: Visconti, Pablo E.. University of Massachussets; Estados UnidosFil: Darszon, Alberto. Universidad Nacional Autónoma de México; MéxicoFil: Treviño, Claudia L.. Universidad Nacional Autónoma de México; MéxicoFil: Buffone, Mariano Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

The mass assembly of galaxy groups and the evolution of the magnitude gap

We investigate the assembly of groups and clusters of galaxies using the Millennium dark matter simulation and the associated gas simulations and semi-analytic catalogues of galaxies. In particular, in order to find an observable quantity that could be used to identify early-formed groups, we study the development of the difference in magnitude between their brightest galaxies to assess the use of magnitude gaps as possible indicators. We select galaxy groups and clusters at redshift z=1 with dark matter halo mass M(R200) > 1E13/h Msun, and trace their properties until the present time (z=0). We consider only the systems with X-ray luminosity L_X> 0.25E42/h^2 erg/s at z=0. While it is true that a large magnitude gap between the two brightest galaxies of a particular group often indicates that a large fraction of its mass was assembled at an early epoch, it is not a necessary condition. More than 90% of fossil groups defined on the basis of their magnitude gaps (at any epoch between 0<z<1) cease to be fossils within 4 Gyr, mostly because other massive galaxies are assembled within their cores, even though most of the mass in their haloes might have been assembled at early times. We show that, compared to the conventional definition of fossil galaxy groups based on the magnitude gap Delta m(12)> 2 (in the R-band, within 0.5R200 of the centre of the group), an alternative criterion Delta m(14)>2.5 (within the same radius) finds 50% more early-formed systems, and those that on average retain their fossil phase longer. However, the conventional criterion performs marginally better at finding early-formed groups at the high-mass end of groups. Nevertheless, both criteria fail to identify a majority of the early-formed systems.Comment: 16 pages, 11 figures, 2 tables. Accepted for publication in MNRA

XMM-Newton and ESO observations of the two unidentified gamma-ray sources 3EG J0616-3310 and 3EG J1249-8330

The limited angular resolution of gamma-ray telescopes prevents a direct identification of the majority of sources detected so far. This is particularly true for the low latitude, probably galactic, ones only 10 % of which has been identified. Most counterparts of the identified low-latitude gamma-ray sources are Isolated Neutron Stars (INS), both radio-loud and radio-quiet (Geminga-like) objects, which are characterised by an extremely high value of the X-ray-to-optical flux ratio f_X/f_opt. Therefore, the systematic X-ray and optical coverage of low-latitude unidentified gamma-ray sources aiming at high f_X/f_opt sources seems one of the most promising ways to spot INS candidate counterparts. Since low latitude sources are heavily affected by the interstellar absorption at both X-ray and optical wavelengths, we have focussed on two middle-latitude, probably galactic, GRO/EGRET sources: 3EG J0616-3310 and 3EG J1249-8330. These two sources, which could belong to a local galactic population, have been selected owing to their relatively good positional accuracy, spectral shape and lack of candidate extragalactic radio counterparts. Here we report on X-ray observations of the two gamma-ray error boxes performed with XMM-Newton and on their optical follow-up carried on with the Wide Field Imager at the ESO/MPG 2.2m telescope. Less than half of the ~300 sources detected by the X-ray coverage have no optical counterparts. Among those, we have selected few interesting sources with f_X/f_opt > 100, which we consider promising INS candidates.Comment: 18 pages, 10 figures, 8 tables. Accepted for publication by Astronomy & Astrophysic

Automating HAZOP studies using D-higraphs

In this paper, we present the use of D-higraphs to perform HAZOP studies. D-higraphs is a formalism that includes in a single model the functional as well as the structural (ontological) components of any given system. A tool to perform a semi-automatic guided HAZOP study on a process plant is presented. The diagnostic system uses an expert system to predict the behavior modeled using D-higraphs. This work is applied to the study of an industrial case and its results are compared with other similar approaches proposed in previous studies. The analysis shows that the proposed methodology fits its purpose enabling causal reasoning that explains causes and consequences derived from deviations, it also fills some of the gaps and drawbacks existing in previous reported HAZOP assistant tools

Coordination of photosynthetic traits across soil and climate gradients

"Least-cost theory" posits that C3 plants should balance rates of photosynthetic water loss and carboxylation in relation to the relative acquisition and maintenance costs of resources required for these activities. Here we investigated the dependency of photosynthetic traits on climate and soil properties using a new Australia-wide trait dataset spanning 528 species from 67 sites. We tested the hypotheses that plants on relatively cold or dry sites, or on relatively more fertile sites, would typically operate at greater CO2 drawdown (lower ratio of leaf internal to ambient CO2 , Ci :Ca ) during light-saturated photosynthesis, and at higher leaf N per area (Narea ) and higher carboxylation capacity (Vcmax 25 ) for a given rate of stomatal conductance to water vapour, gsw . These results would be indicative of plants having relatively higher water costs than nutrient costs. In general, our hypotheses were supported. Soil total phosphorus (P) concentration and (more weakly) soil pH exerted positive effects on the Narea -gsw and Vcmax 25 -gsw slopes, and negative effects on Ci :Ca . The P effect strengthened when the effect of climate was removed via partial regression. We observed similar trends with increasing soil cation exchange capacity and clay content, which affect soil nutrient availability, and found that soil properties explained similar amounts of variation in the focal traits as climate did. Although climate typically explained more trait variation than soil did, together they explained up to 52% of variation in the slope relationships and soil properties explained up to 30% of the variation in individual traits. Soils influenced photosynthetic traits as well as their coordination. In particular, the influence of soil P likely reflects the Australia's geologically ancient low-relief landscapes with highly leached soils. Least-cost theory provides a valuable framework for understanding trade-offs between resource costs and use in plants, including limiting soil nutrients

Immunological characterization of chromogranins A and B and secretogranin II in the bovine pancreatic islet

Antisera against chromogranin A and B and secretogranin II were used for analysing the bovine pancreas by immunoblotting and immunohistochemistry. All three antigens were found in extracts of fetal pancreas by one dimensional immunoblotting. A comparison with the soluble proteins of chromaffin granules revealed that in adrenal medulla and in pancreas antigens which migrated identically in electrophoresis were present. In immunohistochemistry, chromogranin A was found in all pancreatic endocrine cell types with the exception of most pancreatic polypeptide-(PP-) producing cells. For chromogranin B, only a faint immunostaining was obtained. For secretorgranin II, A-and B-cells were faintly positive, whereas the majority of PP-cells exhibited a strong immunostaining for this antigen. These results establish that chromogranins A and B and secretogranin II are present in the endocrine pancreas, but that they exhibit a distinct cellular localization

Transparency of reporting in molecular diagnostics

The major advances made over the past few years in molecular and cell biology are providing a progressively more detailed understanding of the molecular pathways that control normal processes and become dysregulated in disease. This has resulted in the documentation of numerous genetic, epigenetic, transcriptomic, proteomic and metabolomic biomarkers that promise earlier disease detection, more accurate patient stratification and better prognosis. Furthermore, molecular fingerprinting of diseases can be predictive of drug response and so assist with specific targeting of drugs against disease-associated molecules and function