CLLU1 expression has prognostic value in chronic lymphocytic leukemia after first-line therapy in younger patients and in those with mutated IGHV genes.

CLLU1, located at chromosome 12q22, encodes a transcript specific to chronic lymphocytic leukemia and has potential prognostic value. We assessed the value of CLLU1 expression in the LRF CLL4 randomized trial. Samples from 515 patients with chronic lymphocytic leukemia were collected immediately before the start of treatment. After RNA extraction and cDNA synthesis, CLLU1 expression was assessed by quantitative polymerase chain reaction. In total, 247 and 268 samples were identified as having low and high CLLU1 expression, respectively. The median follow-up was 88 months. High CLLU1 expression was significantly correlated with unmutated IGHV genes, ZAP-70 and CD38 positivity, and absence of 13q deletion (all r>0.2, P

First-Principles Study of the Electronic and Magnetic Properties of Defects in Carbon Nanostructures

Understanding the magnetic properties of graphenic nanostructures is instrumental in future spintronics applications. These magnetic properties are known to depend crucially on the presence of defects. Here we review our recent theoretical studies using density functional calculations on two types of defects in carbon nanostructures: Substitutional doping with transition metals, and sp$^3$-type defects created by covalent functionalization with organic and inorganic molecules. We focus on such defects because they can be used to create and control magnetism in graphene-based materials. Our main results are summarized as follows: i)Substitutional metal impurities are fully understood using a model based on the hybridization between the $d$ states of the metal atom and the defect levels associated with an unreconstructed D$_{3h}$ carbon vacancy. We identify three different regimes, associated with the occupation of distinct hybridization levels, which determine the magnetic properties obtained with this type of doping; ii) A spin moment of 1.0 $\mu_B$ is always induced by chemical functionalization when a molecule chemisorbs on a graphene layer via a single C-C (or other weakly polar) covalent bond. The magnetic coupling between adsorbates shows a key dependence on the sublattice adsorption site. This effect is similar to that of H adsorption, however, with universal character; iii) The spin moment of substitutional metal impurities can be controlled using strain. In particular, we show that although Ni substitutionals are non-magnetic in flat and unstrained graphene, the magnetism of these defects can be activated by applying either uniaxial strain or curvature to the graphene layer. All these results provide key information about formation and control of defect-induced magnetism in graphene and related materials.

High-dose therapy and autologous stem cell transplantation in first relapse for diffuse large B cell lymphoma in the rituximab era:an analysis based on data from the European Blood and Marrow Transplantation Registry

Autologous stem cell transplantation (ASCT) consolidation remains the treatment of choice for patients with relapsed diffuse large B cell lymphoma. The impact of rituximab combined with chemotherapy in either first- or second-line therapy on the ultimate results of ASCT remains to be determined, however. This study was designed to evaluate the benefit of ASCT in patients achieving a second complete remission after salvage chemotherapy by retrospectively comparing the disease-free survival (DFS) after ASCT for each patient with the duration of the first complete remission (CR1). Between 1990 and 2005, a total of 470 patients who had undergone ASCT and reported to the European Blood and Bone Transplantation Registry with Medical Essential Data Form B information were evaluated. Of these 470 patients, 351 (74%) had not received rituximab before ASCT, and 119 (25%) had received rituximab before ASCT. The median duration of CR1 was 11 months. The median time from diagnosis to ASCT was 24 months. The BEAM protocol was the most frequently used conditioning regimen (67%). After ASCT, the 5-year overall survival was 63% (95% confidence interval, 58%-67%) and 5-year DFS was 48% (95% confidence interval, 43%-53%) for the entire patient population. Statistical analysis showed a significant increase in DFS after ASCT compared with duration of CR1 (median, 51 months versus 11 months; P < .001). This difference was also highly significant for patients with previous exposure to rituximab (median, 10 months versus not reached; P < .001) and for patients who had experienced relapse before 1 year (median, 6 months versus 47 months; P < .001). Our data indicate that ASCT can significantly increase DFS compared with the duration of CR1 in relapsed diffuse large B cell lymphoma and can alter the disease course even in patients with high-risk disease previously treated with rituximab.

Structural changes in the hippocampus and amygdala at first episode of psychosis

Hippocampus and amygdala changes have been implicated in the pathophysiology and symptomatology of both schizophrenia (SCZ) and bipolar disorder (BD). However relationships between illness course, neuropathological changes and variations in symptomatology remain unclear. This investigation examined the associations between hippocampus and amygdala volumes and symptom dimensions in schizophrenia and bipolar disorder patients after their first episode of psychosis. Symptom severity was associated with decreases in hippocampus/amygdala complex volume across groups. In keeping with previous work bilateral hippocampus and amygdala volume reductions were also identified in the SCZ patients while in BD patients only evidence of amygdala inflation reached significance. The study concludes that there appear to be important relationships between volume changes in the hippocampus and amygdala and dimensions and severity of symptomatology in psychosis. Structural alterations are apparent in both SCZ and BD after first episode of psychosis but present differently in each illness and are more severe in SCZ.

Premorbid IQ in patients with functional psychosis and their first-degree relatives

Numerous studies have found deficits in premorbid IQ in schizophrenic patients, but it is not clear whether this deficit is shared by (a) patients with other functional psychoses, and (b) relatives of these patients. Ninety-one schizophrenic patients, 66 affective psychotic patients (29 schizoaffective and 37 manic or depressed), and 50 normal control subjects were administered the National Adult Reading Test (NART) which provides an estimate of premorbid IQ. The NART was also completed by 85 first-degree relatives of schizophrenic patients and by 65 first-degree relatives of affective psychotic patients. After adjustments were made for sex, social class, ethnicity and years of education, schizophrenic patients had significantly lower premorbid IQ than their relatives, the affective psychotic patients and controls. Manic and depressed patients had significantly lower NART scores than their first-degree relatives, but schizoaffective patients did not, and neither group differed significantly from controls. There was no significant difference in premorbid IQ between patients who had experienced obstetric complications (OC +) and those who had not (OC -). Both OC + and OC - schizophrenic patients differed significantly from their relatives, but the disparity was greatest between OC + patients and their relatives. Relatives of OC + schizophrenic patients had significantly higher IQ than relatives of OC - schizophrenic patients. (C) 2000 Elsevier Science B.V. All rights reserved.

Persistent income poverty and deprivation in the European Union: An analysis of the first three waves of the European Community Household Panel

Poverty research has increasingly focused on persistent income poverty, both as a crucial social indicator and as a target for policy intervention. Such an approach can lead to an identification of a sub-set of poor individuals facing particularly adverse circumstances and/or distinctive problems in escaping from poverty. Here we seek to establish whether, in comparison with cross-sectional measures, persistent poverty measures also provide a better measure of exclusion from a minimally acceptable way of life and relate with other important variables in a logical fashion. Our analysis draws upon the first three waves of the ECHP and shows that a persistent poverty measure does constitute a significant improvement over its cross-sectional counterpart in the explanation of levels of deprivation. Persistent poverty is related to life-style deprivation in a manner that comes close to being uniform across countries. The measure of persistence also conforms to our expectations of how a poverty measure should behave in that, unlike relative income poverty lines, defining the threshold level more stringently enables us to identify progressively groups of increasingly deprived respondents. Overall the persistent poverty measure constitutes a significant advance on cross-sectional income measures. However, there is clearly a great deal relating to the process of accumulation and of erosion of resources, which is not fully captured in the persistent poverty measure. In the absence of such information, there is a great deal to be said for making use of both types of indictors in formulating and evaluating policies while we continue to improve our understanding of longer-term processes.

North European last glacial-interglacial transition (LGIT; 15-9 ka) tephrochronology: extended limits and new events

High-precision correlation of palaeoclimatic and palaeoenvironmental records is crucial for testing hypotheses of synchronous change. Although radiocarbon is the traditional method for dating late Quaternary sedimentary sequences, particularly during the last glacial–interglacial transition (LGIT; 15–9?ka), there are inherent problems with the method, particularly during periods of climate change which are often accompanied by major perturbations in atmospheric radiocarbon content. An alternative method is the use of tephras that act as time-parallel marker horizons. Within Europe, numerous volcanic centres are known to have erupted during the LGIT, providing considerable potential for high-precision correlation independent of past radiocarbon fluctuations. Here we report the first identification of the Vedde Ash and Askja Tephra in Ireland, significantly extending the known provenance of these events. We have also identified two new horizons (the Roddans Port Tephras A and B) and tentatively recognise an additional horizon from Vallensgård Mose (Denmark) that provide crucial additional chronological control for the LGIT. Two phases of the Laacher See Tephra (LST) are reported, the lower Laacher See Tephra (LLST) and probably the C2 phase of the Middle Laacher See Tephra (MLST-C2) indicating a more northeasterly distribution of this fan than reported previously.

Ferroelectricity and isotope effects in hydrogen-bonded KDP crystals

Based on an accurate first principles description of the energetics in H-bonded potassium-dihydrogen-phosphate crystals, we conduct a first study of nuclear quantum effects and of the changes brought about by deuteration. Tunneling is allowed only for clusters involving correlated protons and heavy ion displacements, the main effect of deuteration being a depletion of the proton probability density at the O-H-O bridge center, which in turn weakens its proton-mediated covalent bonding. The ensuing lattice expansion couples self-consistently with the proton off-centering, thus explaining both the giant isotope effect and its close connection with geometrical effects.

cpDNA-RFLP in Ceramium (Rhodophyta): Intraspecific polymorphism and species-level phylogeny

Restriction fragment length polymorphism (RFLP) analysis of chloroplast (cp) DNA is a powerful tool for the study of microevolutionary processes in land plants, yet has not previously been applied to seaweed populations. We used cpDNA-RFLP, detected on Southern blots using labeled total plastid DNA, to search for intraspecific and intrapopulational cpDNA RFLP polymorphism in two species of the common red algal genus Ceramium in Ireland and Britain. In C. botryocarpum one polymorphism was detected in one individual among 18 from two populations. Twenty-six individuals of C. virgatum from five populations at three locations exhibited a total of four haplotypes. One was frequent (80.8% of individuals); the others were rare (7.7, 7.7 and 4.2%) and were private to particular populations. Polymorphism was observed in two populations. The corrected mean was 2.26 +/- 0.36 haplotypes per population, which was within the typical range determined for higher plants using similar techniques. The spatial distribution of haplotypes was heterogeneous, with highly significant population differentiation (P = 0.00018; Fisher's exact test). Intraspecific polymorphism in C. virgatum had no impact on species-level phylogenetic reconstruction. This is the first unequivocal report of both intraspecific and intrapopulational cpDNA-RFLP polymorphism in algae.