Rationale for consolidation to improve progression-free survival in patients with non-Hodgkin's lymphoma: a review of the evidence.

Non-Hodgkin's lymphoma (NHL) comprises both indolent forms, including follicular lymphoma (FL) and marginal zone lymphoma (MZL), and aggressive forms, including diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL). FL and DLBCL are the most common subtypes of indolent and aggressive NHL, respectively. Although these lymphomas exhibit different clinical behaviors and outcomes, the prognosis is negatively affected in both DLBCL and FL by the lack of a complete response (CR) with standard treatment options. The aim of therapy should therefore be achievement of a CR, which is not only associated with longer progression-free survival (PFS) and overall survival times, but is also a prerequisite for a cure, particularly in DLBCL. Consolidation treatment with radioimmunotherapy (RIT) is an innovative treatment approach to increase CR rates. Phase II studies have indicated promising results with yttrium-90 ((90)Y)-ibritumomab tiuxetan and iodine-131 ((131)I)-tositumomab as consolidation following induction therapy for previously untreated patients with advanced FL. More recently, investigators reported a marked increase in CR rates and significant improvements in PFS using standard chemotherapy regimens followed by (90)Y-ibritumomab tiuxetan in a phase III randomized trial in patients with previously untreated FL. Data also suggest that RIT may play a role in the treatment of high-risk DLBCL, with encouraging PFS results from a phase II trial of (90)Y-ibritumomab tiuxetan consolidation following induction with rituximab plus chemotherapy in elderly patients with previously untreated DLBCL. With the higher CR rates and longer PFS times observed in patients with FL and DLBCL, as well as encouraging early data from MZL and MCL consolidation trials, RIT appears to have an important role in the treatment of patients with NHL.

Lifetime of an ocean island volcano feeder zone: constraints from U-Pb dating on coexisting zircon and baddeleyite, and 40Ar/39Ar age determinations, Fuerteventura, Canary Islands

High-precision isotope dilution - thermal ionization mass spectrometry (ID-TIMS) U-Pb zircon and baddeleyite ages from the PX1 vertically layered mafic intrusion Fuerteventura, Canary Islands, indicate initiation of magma crystallization at 22.10 +/- 0.07 Ma. The magmatic activity lasted a minimum of 0.52 Ma. Ar-40/Ar-39 amphibole dating yielded ages from 21.9 +/- 0.6 to 21.8 +/- 0.3, identical within errors to the U-Pb ages, despite the expected 1% theoretical bias between Ar-40/Ar-39 and U-Pb dates. This overlap could result from (i) rapid cooling of the intrusion (i. e., less than the 0.3 to 0.6 Ma 40Ar/39Ar age uncertainties) from closure temperatures (T-c) of zircon (699-988 degrees C) to amphibole (500-600 degrees C); (ii) lead loss affecting the youngest zircons; or (iii) excess argon shifting the plateau ages towards older values. The combination of the Ar-40/Ar-39 and U/Pb datasets implies that the maximum amount of time PX1 intrusion took to cool below amphibole T-c is 0.8 Ma, suggesting PX1 lifetime of 520 000 to 800 000 Ma. Age disparities among coexisting baddeleyite and zircon (22.10 +/- 0.07/0.08/0.15 Ma and 21.58 +/- 0.15/0.16/0.31 Ma) in a gabbro sample from the pluton margin suggest complex genetic relationships between phases. Baddeleyite is found preserved in plagioclase cores and crystallized early from low silica activity magma. Zircon crystallized later in a higher silica activity environment and is found in secondary scapolite and is found close to calcite veins, in secondary scapolite that recrystallised from plagioclase. close to calcite veins. Oxygen isotope delta O-18 values of altered plagioclase are high (+7.7), indicating interaction with fluids derived from host-rock carbonatites. The coexistence of baddeleyite and zircon is ascribed to interaction of the PX1 gabbro with CO2-rich carbonatite-derived fluids released during contact metamorphism.

Insight into oversight : how information commissioners contribute to the achievement of access-to-information policy objectives

This thesis examines how oversight bodies, as part of an ATI policy, contribute to the achievement of the policy's objectives. The aim of the thesis is to see how oversight bodies and the work they do affects the implementation of their respective ATI policies and thereby contributes to the objectives of those policies using a comparative case study approach. The thesis investigates how federal/central government level information commissioners in four jurisdictions - Germany, India, Scotland, and Switzerland - enforce their respective ATI policies, which tasks they carry out in addition to their enforcement duties, the challenges they face in their work and the ways they overcome these. Qualitative data were gathered from primary and secondary documents as well as in 37 semi-structured interviews with staff of the commissioners' offices, administrative officials whose job entails complying with ATI, people who have made ATI requests and appealed to their respective oversight body, and external experts who have studied ATI implementation in their particular jurisdiction. The thesis finds that while the aspect of an oversight body's formal independence that has the greatest impact on its work is resource control and that although the powers granted by law set the framework for ensuring that the administration is properly complying with the policy, the commissioner's leadership style - a component of informal independence - has more influence than formal attributes of independence in setting out how resources are obtained and used as well as how staff set priorities and utilize the powers they are granted by law. The conclusion, therefore, is that an ATI oversight body's ability to contribute to the achievement of the policy's objectives is a function of three main factors: a. commissioner's leadership style; b. adequacy of resources and degree of control the organization has over them; c. powers and the exercise of discretion in using them. In effect, the thesis argues that it is difficult to pinpoint the value of the formal powers set out for the oversight body in the ATI law, and that their decisions on whether and how to use them are more important than the presumed strength of the powers. It also claims that the choices made by the commissioners and their staff regarding priorities and use of powers are determined to a large extent by the adequacy of resources and the degree of control the organization has over those resources. In turn, how the head of the organization leads and manages the oversight body is crucial to both the adequacy of the organization's resources and the decisions made about the use of powers. Together, these three factors have a significant impact on the body's effectiveness in contributing to ATI objectives.

Achievement goals in educational contexts: A social psychology perspective

Research on achievement goals usually defines mastery goals as the desire to acquire knowledge, and performance goals as the desire to outperform (or not to underperform) others. Educational contexts are most of the time social contexts, involving various persons and groups, of various hierarchical positions, and various cultural and ideological contexts. Surprisingly, most research in the achievement goal field has been conducted at an individual level of analysis. In the present paper, we will review the social consequences and antecedents of goal endorsement. This research indicates that goals strongly affect the way one behaves with co-learners. Moreover, it suggests that more than merely individual dispositions, goals reflect the social relation students have with other persons, institutions, and with the society to which they belong. We conclude this paper by setting an agenda for future achievement goal research.

Clinal variation in a brown lemur (Eulemur spp.) hybrid zone: Combining morphological, genetic and climatic data to examine stability.

Studies of hybrid zones can inform our understanding of reproductive isolation and speciation. Two species of brown lemur (Eulemur rufifrons and E. cinereiceps) form an apparently stable hybrid zone in the Andringitra region of south-eastern Madagascar. The aim of this study was to identify factors that contribute to this stability. We sampled animals at 11 sites along a 90-km transect through the hybrid zone and examined variation in 26 microsatellites, the D-loop region of mitochondrial DNA, six pelage and nine morphological traits; we also included samples collected in more distant allopatric sites. Clines in these traits were noncoincident, and there was no increase in either inbreeding coefficients or linkage disequilibrium at the centre of the zone. These results could suggest that the hybrid zone is maintained by weak selection against hybrids, conforming to either the tension zone or geographical selection-gradient model. However, a closer examination of clines in pelage and microsatellites indicates that these clines are not sigmoid or stepped in shape but instead plateau at their centre. Sites within the hybrid zone also occur in a distinct habitat, characterized by greater seasonality in precipitation and lower seasonality in temperature. Together, these findings suggest that the hybrid zone may follow the bounded superiority model, with exogenous selection favouring hybrids within the transitional zone. These findings are noteworthy, as examples supporting the bounded superiority model are rare and may indicate a process of ecologically driven speciation without geographical isolation.

Groundwater fluctuations and footslope ferricrete soils in the humid tropical zone of southern Cameroon

This paper discusses the relationship between the differentiation of ferruginous accumulations and the variable water saturation of footslope soil patterns. An analysis of the slope morphology of a typical hill in the forest zone of southern Cameroon and a seasonal survey of the levels of groundwaters, springs and rivers were considered in relation to the petrology of different soil patterns. The study site is a tabular hillock whose slopes present a progressive development from steep to gentle slopes. The variable residence time of water within the soil, creating an alternation of reducing and oxidizing conditions, affects oil chemistry, structure and lateral extension of the soil patterns. The ferruginous soil patterns, being formed on the footslopes, gradually increase in extent with decreasing slope angle and the relative rise of the groundwater level. The steep footslopes, where groundwater has a shorter residence time, show a soft mottled clay pattern, restricted to the bottom part of the slope. The moderate footslopes exhibit a deep permanent and a temporary perched groundwater table. The latter, with its regular capillary fringe, contributes to more reducing conditions within isolated domains in the soil patterns, and thus to the alternation with oxidizing conditions, generating a continuous hard soil pattern (massive carapace). The more gently dipping footslopes exhibit groundwater levels near the surface and also a significant amplitude of groundwater fluctuation. Iron, previously accumulated in moderate footslope patterns, is reduced, remobilized, and leached. The soil patterns formed develop into a variegated carapace, more extended along the slope, containing less iron, but nevertheless more hardened, due to the important fluctuations of the groundwater table. These patterns are limited to the zone of groundwater fluctuation and deteriorate as the water fluctuation zone recedes. Copyright (c) 2005 John Wiley & Sons, Ltd.

Projections de l'utilisation des lits dans le canton de Vaud : hôpitaux de zone, 1990-2010

La projection utilise toujours le programme de simulation SIMULIT, dans sa treizième version. (...) Seule l'évolution démographique a été considérée dans les projections du nombre de lits: aucune des autres variables susceptibles de changer dans le futur n'a été prise en compte, ni celle en relation avec l'activité hospitalière elle-même (modification des taux d'hospitalisation, des durées de séjour, etc.), ni celles concernant l'état de santé de la population (modification de l'incidence ou de la prévalence des maladies). En d'autres termes, cette projection montre l'effet de l'évolution démographique sur l'activité hospitalière, si les caractéristiques de cette activité devaient rester celles observées dans les années 80. Il ne s'agit donc pas d'une prévision. [Auteurs, p. 1]

Restoration of lymphoid organ integrity through the interaction of lymphoid tissue-inducer cells with stroma of the T cell zone.

The generation of lymphoid microenvironments in early life depends on the interaction of lymphoid tissue-inducer cells with stromal lymphoid tissue-organizer cells. Whether this cellular interface stays operational in adult secondary lymphoid organs has remained elusive. We show here that during acute infection with lymphocytic choriomeningitis virus, antiviral cytotoxic T cells destroyed infected T cell zone stromal cells, which led to profound disruption of secondary lymphoid organ integrity. Furthermore, the ability of the host to respond to secondary antigens was lost. Restoration of the lymphoid microanatomy was dependent on the proliferative accumulation of lymphoid tissue-inducer cells in secondary lymphoid organs during the acute phase of infection and lymphotoxin alpha(1)beta(2) signaling. Thus, crosstalk between lymphoid tissue-inducer cells and stromal cells is reactivated in adults to maintain secondary lymphoid organ integrity and thereby contributes to the preservation of immunocompetence.

Association of T-zone reticular networks and conduits with ectopic lymphoid tissues in mice and humans.

Ectopic or tertiary lymphoid tissues (TLTs) are often induced at sites of chronic inflammation. They typically contain various hematopoietic cell types, high endothelial venules, and follicular dendritic cells; and are organized in lymph node-like structures. Although fibroblastic stromal cells may play a role in TLT induction and persistence, they have remained poorly defined. Herein, we report that TLTs arising during inflammation in mice and humans in a variety of tissues (eg, pancreas, kidney, liver, and salivary gland) contain stromal cell networks consisting of podoplanin(+) T-zone fibroblastic reticular cells (TRCs), distinct from follicular dendritic cells. Similar to lymph nodes, TRCs were present throughout T-cell-rich areas and had dendritic cells associated with them. They expressed lymphotoxin (LT) β receptor (LTβR), produced CCL21, and formed a functional conduit system. In rat insulin promoter-CXCL13-transgenic pancreas, the maintenance of TRC networks and conduits was partially dependent on LTβR and on lymphoid tissue inducer cells expressing LTβR ligands. In conclusion, TRCs and conduits are hallmarks of secondary lymphoid organs and of well-developed TLTs, in both mice and humans, and are likely to act as important scaffold and organizer cells of the T-cell-rich zone.

Inverse metamorphic zonation in very low-grade Tibetan zone series of SE Zanskar and its tectonic consequences (NW India, Himalaya)

The metamorphism of the carbonate rocks of the SE Zanskar Tibetan zone has been studied by `'illite crystallinity'' and calcite-dolomite thermometry. The epizonal Zangla unit overlies the anchizonal Chumik unit. This discontinuous inverse zonation demonstrates a late to post-metamorphic thrust of the first unit over the second. The studied area underwent a complex tectonic history: - The tectonic units were stacked from the NE to the SW, generating recumbent folds, NE dipping thrusts and the regional metamorphism. The compressive movements were active under lower temperature conditions, resulting in late thrusts that disturbed the metamorphic zonation. The discontinuous inverse metamorphic zonation dates from this phase. - A NE vergent backfolding phase occurred at lower temperature conditions. It caused the uplift of more metamorphic levels. - A late extensional phase is revealed by the presence of NE dipping low angle normal faults, and a major high angle fault, the Sarchu fault. The low angle normal faults locally run along earlier thrusts (composite tectonic contacts). Their throw has been sufficient to reset a normal stratigraphic superposition (young layers overlying old ones), but insufficient to erase the inverse metamorphic relationship. However, the combined action of backfolding and normal faulting can locally lessen, or even cancel, the inverse metamorphic superposition. After deduction of the normal fault translation, the vertical component of the original thrust displacement through stratigraphy is 400 m, which is a value far too low to explain the temperature difference between the two units. The horizontal component of displacement is therefore far more important than the vertical one. The regional distribution of metamorphism within the Zangla unit points out to an anchizonal front and an epizonal inner part. This fact is in agreement with nappe tectonics.

Estimating vadose zone hydraulic properties using ground penetrating radar: The impact of prior information

A number of geophysical methods, such as ground-penetrating radar (GPR), have the potential to provide valuable information on hydrological properties in the unsaturated zone. In particular, the stochastic inversion of such data within a coupled geophysical-hydrological framework may allow for the effective estimation of vadose zone hydraulic parameters and their corresponding uncertainties. A critical issue in stochastic inversion is choosing prior parameter probability distributions from which potential model configurations are drawn and tested against observed data. A well chosen prior should reflect as honestly as possible the initial state of knowledge regarding the parameters and be neither overly specific nor too conservative. In a Bayesian context, combining the prior with available data yields a posterior state of knowledge about the parameters, which can then be used statistically for predictions and risk assessment. Here we investigate the influence of prior information regarding the van Genuchten-Mualem (VGM) parameters, which describe vadose zone hydraulic properties, on the stochastic inversion of crosshole GPR data collected under steady state, natural-loading conditions. We do this using a Bayesian Markov chain Monte Carlo (MCMC) inversion approach, considering first noninformative uniform prior distributions and then more informative priors derived from soil property databases. For the informative priors, we further explore the effect of including information regarding parameter correlation. Analysis of both synthetic and field data indicates that the geophysical data alone contain valuable information regarding the VGM parameters. However, significantly better results are obtained when we combine these data with a realistic, informative prior.

Programming of marginal zone B-cell fate by basic Kruppel-like factor (BKLF/KLF3).

Splenic marginal zone (MZ) B cells are a lineage distinct from follicular and peritoneal B1 B cells. They are located next to the marginal sinus where blood is released. Here they pick up antigens and shuttle the load onto follicular dendritic cells inside the follicle. On activation, MZ B cells rapidly differentiate into plasmablasts secreting antibodies, thereby mediating humoral immune responses against blood-borne type 2 T-independent antigens. As Krüppel-like factors are implicated in cell differentiation/function in various tissues, we studied the function of basic Krüppel-like factor (BKLF/KLF3) in B cells. Whereas B-cell development in the bone marrow of KLF3-transgenic mice was unaffected, MZ B-cell numbers in spleen were increased considerably. As revealed in chimeric mice, this occurred cell autonomously, increasing both MZ and peritoneal B1 B-cell subsets. Comparing KLF3-transgenic and nontransgenic follicular B cells by RNA-microarray revealed that KLF3 regulates a subset of genes that was similarly up-regulated/down-regulated on normal MZ B-cell differentiation. Indeed, KLF3 expression overcame the lack of MZ B cells caused by different genetic alterations, such as CD19-deficiency or blockade of B-cell activating factor-receptor signaling, indicating that KLF3 may complement alternative nuclear factor-κB signaling. Thus, KLF3 is a driving force toward MZ B-cell maturation.