Evolving characteristics and outcome of secondary acute promyelocytic leukemia (APL): A prospective analysis by the French-Belgian-Swiss APL group.

BACKGROUND: Reports of patients with secondary acute promyelocytic leukemia (APL) have increased in recent years, particularly for those who received treatment with mitoxantrone, and retrospective studies have suggested that their characteristics and outcomes were similar to those of patients with de novo APL. METHODS: The authors investigated patients with de novo and secondary APL who were included in the ongoing APL-2006 trial. Patients with secondary APL who were included in that trial also were compared with a previous retrospective cohort of patients with secondary APL. RESULTS: In the APL-2006 trial, 42 of 280 patients (15%) had secondary APL. Compared with the retrospective cohort, patients with secondary APL in the APL-2006 trial had a lower incidence of prior breast carcinoma (35.7% vs 57%; P = .03) and a higher incidence of prior prostate carcinoma (26.2% vs 4.7%; P < .001). Treatment of the primary tumor in the APL-2006 trial less frequently included combined radiochemotherapy (28.6% vs 47.2%; P = .044) and no mitoxantrone (0% vs 46.7%; P = .016) but more frequently included anthracyclines (53.3% vs 38.3%; P = .015). In the APL-2006 trial, patients who had secondary APL, compared with those who had de novo APL, were older (mean, 60.2 years vs 48.7 years, respectively; P < .0001) but had a similar complete response rate (97.6% vs 90.3%, respectively), cumulative incidence of relapse (0% vs 1.8%, respectively), and overall survival (92.3% vs 90.9%, respectively) at 18 months. CONCLUSIONS: Although the incidence of secondary APL appears to be stable over time, evolving strategies for the treatment of primary cancers have reduced its occurrence among breast cancer patients but have increased its incidence among patients with prostate cancer. The current results confirm prospectively that patients with secondary APL have characteristics and outcomes similar to those of patients with de novo APL. Cancer 2015;121:2393-2399. © 2015 American Cancer Society.

Biological variation of established and novel biomarkers for atherosclerosis: Results from a prospective, parallel-group cohort study.

BACKGROUND: Biomarkers are a promising tool for the management of patients with atherosclerosis, but their variation is largely unknown. We assessed within-subject and between-subject biological variation of biomarkers in peripheral artery disease (PAD) patients and healthy controls, and defined which biomarkers have a favorable variation profile for future studies. METHODS: Prospective, parallel-group cohort study, including 62 patients with stable PAD (79% men, 65±7years) and 18 healthy control subjects (44% men, 57±7years). Blood samples were taken at baseline, and after 3-, 6-, and 12-months. We calculated within-subject (CVI) and between-subject (CVG) coefficients of variation and intra-class correlation coefficient (ICC). RESULTS: Mean levels of D-dimer, hs-CRP, IL-6, IL-8, MMP-9, MMP-3, S100A8/A9, PAI-1, sICAM-1, and sP-selectin levels were higher in PAD patients than in healthy controls (P≤.05 for all). CVI and CVG of the different biomarkers varied considerably in both groups. An ICC≥0.5 (indicating moderate-to-good reliability) was found for hs-CRP, D-Dimer, E-selectin, IL-10, MCP-1, MMP-3, oxLDL, sICAM-1 and sP-selectin in both groups, for sVCAM in healthy controls and for MMP-9, PAI-1 and sCD40L in PAD patients. CONCLUSIONS: Single biomarker measurements are of limited utility due to large within-subject variation, both in PAD patients and healthy subjects. D-dimer, hs-CRP, MMP-9, MMP-3, PAI-1, sP-selectin and sICAM-1 are biomarkers with both higher mean levels in PAD patients and a favorable variation profile making them most suitable for future studies.

Emergent power hierarchies and group performance (Published online: 7 Oct. 2014)

In newly formed groups, informal hierarchies emerge automatically and readily. In this study, we argue that emergent group hierarchies enhance group performance (Hypothesis 1) and we assume that the more the power hierarchy within a group corresponds to the task-competence differences of the individual group members, the better the group performs (Hypothesis 2). Twelve three-person groups and 28 four-person groups were investigated while solving the Winter Survival Task. Results show that emerging power hierarchies positively impact group performance but the alignment between task-competence and power hierarchy did not affect group performance. Thus, emergent power hierarchies are beneficial for group performance and although they were on average created around individual group members' competence, this correspondence was not a prerequisite for better group performance.

Chemical and mineralogical alteration of ceramics from a Late Bronze Age kiln at Kommos, Crete: the effect on the formation of a reference group

The formation of reference groups comprises an important procedure in chemical provenance studies of archaeological pottery. Material from ancient kilns is thought to be especially suitable for reference groups, as it comprises a definite unit of past production. Pottery from the Late Minoan IA kiln excavated at Kommos, Crete was analysed in order to produce a reference group in this important area of Minoan ceramic production. The samples were characterized by a combination of techniques providing information on the chemistry, mineralogy and microstructure of the ceramic body. Initially, the study was unable to establish, in a straightforward manner, a chemical reference group. Different ceramic pastes and a range of selective alterations and contaminations, affected by variable firing temperatures and burial environment, were shown to be responsible for the compositional variability. Procedures are described to compensate for such alterations and the perturbations in the data that they produce.

High mobility group box 1 protein (HMGB1) : a pathogenic role in preeclampsia

Introduction : la Physiopathologie maternelle de la prééclampsie s'associe typiquement à un état inflammatoire systémique modéré. La protéine "high mobility group box 1" (HMGB-1) est une protéine nucléaire ubiquitaire. En cas de stress cellulaire, elle est relâchée dans le milieu extrace llua li re et peut ainsi exercer son activité pro-inflammatoire. En cas de prééclampsie, le liquide amniotique et le cytoplasme des cellules trophoblastiques contiennent des quantités anormalement élevées de HMGB-1, mais il n'est toujours pas universellement admis que ces concentrations se retrouvent dans le sang maternel. Méthodes : nous avons recruté 32 femmes au troisième trimestre de grossesse, 16 avec et 16 sans prééclampsie. Nous avons également observé 16 femmes non enceintes et en bonne santé, appariées selon l'âge avec les femmes enceintes. Nous avons mesuré la concentration sérique de HMGB-1 chez les femmes enceintes avant, puis 24-48 heures après leur accouchement, en utilisant un kit ELISA commercial. Le même dosage a été réalisé chez les femmes non enceintes, mais à une seule reprise, au moment de leur inclusion dans l'étude. Résultats : le jour de leur inclusion dans l'étude, la concentration médiane [intervalle interquartile] de HMGB-1 chez les femmes enceintes prééclamptiques était de 2.1 ng/ml [1.1 - 3.2], de 1.1 [1.0-1.2] chez les grossesses saines (p < 0.05 vs groupe prééclamptiques) et de 0.6 [0.5 - 0.8] chez les patientes non enceintes (p < 0.01 vs deux autres groupes). Pour les deux groupes de femmes enceintes, les concentrations mesurées en post-partum ne variaient pas significativement de celles mesurées avant l'accouchement. Conclusion : avec ou sans prééclampsie, le troisième triemstre de la grossesse est associé à une élévation des taux circulants de HMGB-1. Cette augmentation est exagérée en cas de prééclampsie. L'origine de ces concentrations élevées reste à déterminer, mais elle semble impliquer d'autres organes que le placenta lui-même.

'And the best essay is...' : Extended contact and cross-group friendships at school

We conducted one experimental intervention based on extended contact principles aimed at fostering the formation of cross-group friendships within educational settings. Italian school children took part in a school competition for the best essay on personal experiences of cross-group friendships with immigrants, to be written in small groups. This manipulation was intended to favour the exchange of personal positive cross-group experiences, thus capitalizing on the benefits of extended contact. In the control condition, participants wrote an essay on friendship, without reference to cross-group relations. Results revealed that children who took part in the intervention reported a higher number of outgroup friends 3 months later. This indirect effect was sequentially mediated by pro-contact ingroup and outgroup norms and by outgroup contact behavioural intentions. This study provides experimental evidence that interventions based on extended contact can foster cross-group friendship formation. Theoretical and practical implications of the findings are discussed.

Clinical Application of Prognostic Gene Expression Signature in Fusion Gene-Negative Rhabdomyosarcoma: A Report from the Children's Oncology Group.

PURPOSE: Pediatric rhabdomyosarcoma (RMS) has two common histologic subtypes: embryonal (ERMS) and alveolar (ARMS). PAX-FOXO1 fusion gene status is a more reliable prognostic marker than alveolar histology, whereas fusion gene-negative (FN) ARMS patients are clinically similar to ERMS patients. A five-gene expression signature (MG5) previously identified two diverse risk groups within the fusion gene-negative RMS (FN-RMS) patients, but this has not been independently validated. The goal of this study was to test whether expression of the MG5 metagene, measured using a technical platform that can be applied to routine pathology material, would correlate with outcome in a new cohort of patients with FN-RMS. EXPERIMENTAL DESIGN: Cases were taken from the Children's Oncology Group (COG) D9803 study of children with intermediate-risk RMS, and gene expression profiling for the MG5 genes was performed using the nCounter assay. The MG5 score was correlated with clinical and pathologic characteristics as well as overall and event-free survival. RESULTS: MG5 standardized score showed no significant association with any of the available clinicopathologic variables. The MG5 signature score showed a significant correlation with overall (N = 57; HR, 7.3; 95% CI, 1.9-27.0; P = 0.003) and failure-free survival (N = 57; HR, 6.1; 95% CI, 1.9-19.7; P = 0.002). CONCLUSIONS: This represents the first, validated molecular prognostic signature for children with FN-RMS who otherwise have intermediate-risk disease. The capacity to measure the expression of a small number of genes in routine pathology material and apply a simple mathematical formula to calculate the MG5 metagene score provides a clear path toward better risk stratification in future prospective clinical trials. Clin Cancer Res; 21(20); 4733-9. ©2015 AACR.

The effect of skewness and kurtosis on the Kenward-Roger approximation when group distributions differ

This study examined the independent effect of skewness and kurtosis on the robustness of the linear mixed model (LMM), with the Kenward-Roger (KR) procedure, when group distributions are different, sample sizes are small, and sphericity cannot be assumed. Methods: A Monte Carlo simulation study considering a split-plot design involving three groups and four repeated measures was performed. Results: The results showed that when group distributions are different, the effect of skewness on KR robustness is greater than that of kurtosis for the corresponding values. Furthermore, the pairings of skewness and kurtosis with group size were found to be relevant variables when applying this procedure. Conclusions: With sample sizes of 45 and 60, KR is a suitable option for analyzing data when the distributions are: (a) mesokurtic and not highly or extremely skewed, and (b) symmetric with different degrees of kurtosis. With total sample sizes of 30, it is adequate when group sizes are equal and the distributions are: (a) mesokurtic and slightly or moderately skewed, and sphericity is assumed; and (b) symmetric with a moderate or high/extreme violation of kurtosis. Alternative analyses should be considered when the distributions are highly or extremely skewed and samples sizes are small.

The new final Clinical Skills examination in human medicine in Switzerland: Essential steps of exam development, implementation and evaluation, and central insights from the perspective of the national Working Group.

OBJECTIVE: Since 2011, the new national final examination in human medicine has been implemented in Switzerland, with a structured clinical-practical part in the OSCE format. From the perspective of the national Working Group, the current article describes the essential steps in the development, implementation and evaluation of the Federal Licensing Examination Clinical Skills (FLE CS) as well as the applied quality assurance measures. Finally, central insights gained from the last years are presented. METHODS: Based on the principles of action research, the FLE CS is in a constant state of further development. On the foundation of systematically documented experiences from previous years, in the Working Group, unresolved questions are discussed and resulting solution approaches are substantiated (planning), implemented in the examination (implementation) and subsequently evaluated (reflection). The presented results are the product of this iterative procedure. RESULTS: The FLE CS is created by experts from all faculties and subject areas in a multistage process. The examination is administered in German and French on a decentralised basis and consists of twelve interdisciplinary stations per candidate. As important quality assurance measures, the national Review Board (content validation) and the meetings of the standardised patient trainers (standardisation) have proven worthwhile. The statistical analyses show good measurement reliability and support the construct validity of the examination. Among the central insights of the past years, it has been established that the consistent implementation of the principles of action research contributes to the successful further development of the examination. CONCLUSION: The centrally coordinated, collaborative-iterative process, incorporating experts from all faculties, makes a fundamental contribution to the quality of the FLE CS. The processes and insights presented here can be useful for others planning a similar undertaking.

p-Nitrobenzyloxycarbonyl (pNZ) as Temporary Na-Protecting Group for Mild Solid-Phase Peptide Synthesis. Avoiding Diketopiperazine and Aspartimide Formation

p-Nitrobenzyloxycarbonyl was used as temporary protecting group for the -amino function in solid-phase peptide synthesis. The corresponding derivatives are solids, easy to be synthesized, and perform well in the solid-phase mode. pNZ is removed in practical neutral conditions in the presence of catalytic amounts of acid. They are orthogonal with the most common protecting groups used in peptide chemistry. They are specially useful in combination with Fmoc chemistry to overcome those side reactions associated with the used of the piperidine such DKP and aspartiimide formation. The flexibility of pNZ can be very useful for the preparation of libraries of small organic molecules.

Incidence and Outcome of Group B Streptococcal Sepsis in Infants in Switzerland.

The incidence and outcome of group B streptococcal (GBS) sepsis were assessed prospectively between September 2011 and February 2015 in all tertiary care pediatric hospitals of Switzerland. We describe a low incidence of GBS early-onset sepsis (0.12/1000 livebirths) and a predominance of GBS late-onset sepsis (0.36/1000 livebirths), a pattern that has not been reported in other countries.

Collaborative group membership and access control for JXTA

Peer-reviewed

Tan cerca, tan lejos: Aldo Rossi y el Grupo 2C. Arquitectura, ideología y disidencias en la Barcelona de los 70 = So close, so far : Aldo Rossi and the 2C Group. Architecture, ideology and dissents in the Barcelona of the 70s

The Catalan reception of the 1966 manifestos by Robert Venturi and Aldo Rossi marks the scenario of a breakup: while North America debates about the architectural shape as a linguistic structure, Italy dips its roots in the Modern Movement tradition as an origin for a new temporal and ideological architectural dimension. The first contacts between Rossi and Spain verify this search and allow the Italian to construct common itineraries with some architects from Barcelona. From these exchanges the 2C group will be born, taking part on typical vanguardist mechanisms: they will publish the magazine, 2C. The construction of the city (1972-1985), they will attend the XV Triennale di Milano in 1973 with the Torres Clavé Plan (1971) and the Aldo Rossi + 21 Spanish architects exhibition (1975) while he will organize the three issues of the Seminarios Internacionales de Arquitectura Contemporánea (S.I.AC.) which took place in Santiago, Sevilla and Barcelona between 1976 and 1980. In front of the unfolding of the firsts, the American contacts of Federico Correa, Oriol Bohigas, Lluís Domènech and the PER studio or the teaching work of Rafael Moneo from Barcelona since 1971, allow to draw replica itineraries with the foundation of the magazine Arquitecturas Bis (1974-1985), the organization of the meetings between international publications such as Lotus and Oppositions in Cadaqués (1975) and New York (1977), while stablishing exchanges with members of the Five Architects. Replicas that in 1976 conduct the initial ideological affirmations between Rossi and the 2C group towards irreconcilable distancing. Verifying the itinerary of the journey that the Italian leads from the Italian resistance towards the American backing down is part of the aim of this article