Asparaginase-associated pancreatitis: a study on phenotype and genotype in the NOPHO ALL2008 protocol.

Asparaginase (ASP)-associated pancreatitis (AAP) occurs during acute lymphoblastic leukemia treatment. Among 1285 children (1.0-17.9 years) diagnosed during July 2008-December 2014 and treated according to the Nordic/Baltic ALL2008 protocol, 86 (cumulative incidence=6.8%) developed AAP. Seventy-three cases were severe (diagnostic AAP criteria persisting >72 h) and 13 mild. Cases were older than controls (median: 6.5 vs 4.5 years; P=0.001). Pseudocysts developed in 28%. Of the 20 re-exposed to ASP, 9 (45%) developed a second AAP. After a median follow-up of 2.3 years, 8% needed permanent insulin therapy, and 7% had recurrent abdominal pain. Germline DNA on 62 cases and 638 controls was genotyped on Omni2.5exome-8-v1.2 BeadChip arrays. Overall, the ULK2 variant rs281366 showed the strongest association with AAP (P=5.8 × 10-7; odds ratio (OR)=6.7). Cases with the rs281366 variant were younger (4.3 vs 8 years; P=0.015) and had lower risk of AAP-related complications (15% vs 43%; P=0.13) compared with cases without this variant. Among 45 cases and 517 controls <10 years, the strongest associations with AAP were found for RGS6 variant rs17179470 (P=9.8 × 10-9; OR=7.3). Rs281366 is located in the ULK2 gene involved in autophagy, and RGS6 regulates G-protein signaling regulating cell dynamics. More than 50% of AAP cases <10 years carried one or both risk alleles.

Genomic profiling of thousands of candidate polymorphisms predicts risk of relapse in 778 Danish and German childhood acute lymphoblastic leukemia patients.

Childhood acute lymphoblastic leukemia survival approaches 90%. New strategies are needed to identify the 10-15% who evade cure. We applied targeted, sequencing-based genotyping of 25 000 to 34 000 preselected potentially clinically relevant single-nucleotide polymorphisms (SNPs) to identify host genome profiles associated with relapse risk in 352 patients from the Nordic ALL92/2000 protocols and 426 patients from the German Berlin-Frankfurt-Munster (BFM) ALL2000 protocol. Patients were enrolled between 1992 and 2008 (median follow-up: 7.6 years). Eleven cross-validated SNPs were significantly associated with risk of relapse across protocols. SNP and biologic pathway level analyses associated relapse risk with leukemia aggressiveness, glucocorticosteroid pharmacology/response and drug transport/metabolism pathways. Classification and regression tree analysis identified three distinct risk groups defined by end of induction residual leukemia, white blood cell count and variants in myeloperoxidase (MPO), estrogen receptor 1 (ESR1), lamin B1 (LMNB1) and matrix metalloproteinase-7 (MMP7) genes, ATP-binding cassette transporters and glucocorticosteroid transcription regulation pathways. Relapse rates ranged from 4% (95% confidence interval (CI): 1.6-6.3%) for the best group (72% of patients) to 76% (95% CI: 41-90%) for the worst group (5% of patients, P<0.001). Validation of these findings and similar approaches to identify SNPs associated with toxicities may allow future individualized relapse and toxicity risk-based treatments adaptation.

Adolescents' health identities: a qualitative and theoretical study of health education courses.

In this paper we highlight the role of health identity in health education for adolescents. In school-based approaches to health education, it is often difficult to present health information and health communication in ways that make sense and appeal to adolescents. The concept of health identity has the potential of providing an analytical framework as well as practical recommendations for these issues and problem areas. The paper reports on an empirical study of elements of health identity in the context of health courses for adolescents--using interview data, observation studies and a theoretical construction focussing on self-observation, horizons of significance, expectational structures and social imaginaries. We present our findings in four main themes: 1) Adolescents' health identities are observed and developed when things matter, 2) Adolescents' health identities are observed and developed in relational contexts, 3) Adolescents' health identities are developed on the basis of observations of past, present and future health and 4) Adolescents' health identities are clearly defined. The paper provides health practitioners with important knowledge about why and how health-educational approaches should focus on health identity in order to provide conditions that create a significant health educating effect for all adolescents--not just for those who are already healthy.

Microsatellite markers for the endangered fir Abies guatemalensis (Pinaceae).

Eight newly developed polymorphic microsatellite markers are presented for Abies guatemalensis Rehder, an endangered tree endemic to Mexico and Central America. These microsatellite markers are useful for evaluating the population genetics of the species which is threatened by greenery poaching in natural populations. Novel conservation plans are needed to secure a more sustainable use strategy and to preserve the genetic diversity of the species.

Ordering mechanisms in triblock copolymers.

The ordering mechanisms for an ABC triblock copolymer system are studied using self-consistent field theory. We find a two-phase mechanism, similar to what has been suggested experimentally (two-step mechanism). Analysis of free energy components shows that the two-phase process comes about through a competition between stretching energy and interfacial energy. The mechanism is found to be sufficiently robust so as to make it potentially useful for device applications.

Delocalizing transition of Bose-Einstein condensates in optical lattices.

A Bose-Einstein condensate trapped in a two-dimensional optical lattice exhibits an abrupt transition manifested by the macroscopic wave function changing character from spatially localized to extended. Resulting from a bifurcation, this irreversible transition takes place as the interwell potential barrier is adiabatically decreased below a critical value. This is in sharp contrast to the corresponding one-dimensional case where such a bifurcation is absent and the extent of a localized mode is continuously tunable. We demonstrate how these phenomena can be experimentally explored.

Efficient computation of the structural phase behavior of block copolymers.

A numerical implementation of self-consistent mean-field theory for the structural phase behavior of block copolymers is proposed. Our scheme does not require a priori assumptions of the underlying mesoscopic symmetries. The method potentially enables us to characterize, with high accuracy, the structural phase diagram of block copolymers with significant architectural complexity. We illustrate the method by applying it to a triblock copolymer system.

Os penis of the rat. V. The distal cartilage process.

The morphogenesis and morphology of the distally positioned cartilage of the os penis, the processus cartilagineus, are described in rats aged from 1 to 100 days. Based on observations of metachromacy of the process stained with toluidine blue it was found that a processus cartilagineus only exists in the period between 35 and 50 days of age. Before 35 days, the structure consists of connective tissue proper, and after 50 days the cartilage starts to calcify partially. The present paper also initiates studies of experimentally caused alterations of the normal development of the processus cartilagineus by subjecting 35-day-old rats to castration, with subsequent sacrifice at 100 days. Castration at that age causes a complete interruption of normal development of the processus cartilagineus as the structure in 100-day-old castrated rats has distinct morphological characteristics in common with those of 35-day-old normal rats. The present paper, thus, confirms that normal development of the processus cartilagineus seems to be male-hormone-dependent.