Event-related potentials and changes of brain rhythm oscillations during working memory activation in patients with first-episode psychosis.

Background: Earlier contributions have documented significant changes in sensory, attention-related endogenous event-related potential (ERP) components and θ band oscillatory responses during working memory activation in patients with schizophrenia. In patients with first-episode psychosis, such studies are still scarce and mostly focused on auditory sensory processing. The present study aimed to explore whether subtle deficits of cortical activation are present in these patients before the decline of working memory performance. Methods: We assessed exogenous and endogenous ERPs and frontal θ event-related synchronization (ERS) in patients with first-episode psychosis and healthy controls who successfully performed an adapted 2-back working memory task, including 2 visual n-backworking memory tasks as well as oddball detection and passive fixation tasks. Results: We included 15 patients with first-episode psychosis and 18 controls in this study. Compared with controls, patients with first-episode psychosis displayed increased latencies of early visual ERPs and phasic θ ERS culmination peak in all conditions. However, they also showed a rapid recruitment of working memory-related neural generators, even in pure attention tasks, as indicated by the decreased N200 latency and increased amplitude of sustained θ ERS in detection compared with controls. Limitations: Owing to the limited sample size, no distinction was made between patients with first-episode psychosis with positive and negative symptoms. Although we controlled for the global load of neuroleptics, medication effect cannot be totally ruled out. Conclusion: The present findings support the concept of a blunted electroencephalographic response in patients with first-episode psychosis who recruit the maximum neural generators in simple attention conditions without being able to modulate their brain activation with increased complexity of working memory tasks.

Follicular lymphoma at relapse after rituximab containing regimens: comparison of time to event intervals prior to and after (90) Y-ibritumomab-tiuxetan.

Radioimmunotherapies with Zevalin® (RIT-Z) showed encouraging results in patients with relapsed/refractory follicular lymphoma (FL), leading frequently to failure-free intervals longer than those achieved by the last previous therapy. We compared time-to-event variables obtained before and after RIT-Z in patients with relapsed FL, previously exposed to rituximab. All patients with relapsed non-transformed, non-refractory, non-rituximab-naïve FL who have been treated with RIT-Z in two different centres in Europe were included. Staging and response were assessed by contrast-enhanced CT in all patients; PET/CT was performed according to local availability. Event-free survival (EFS) and time to next treatment (TTNT) following the last previous therapy and after RIT-Z were compared. Pre-therapy characteristics were tested in univariate analyses for prediction of outcomes. A description of the patterns of relapse was also provided. Among 70 patients treated, only 16 fulfilled the inclusion criteria. They were treated with a median of 3 prior lines of chemo-immunotherapies, including a median of 2 rituximab-containing regimens; 6 patients had undergone myeloablative chemotherapy with autologous stem cell rescue (ASCT). Overall response rates were 10 (62%) CR/CRu, 3 (19%) PR and 3 (19%) PD; response rates were similar in patients with prior ASCT. After RIT-Z only few patients obtained EFS and TTNT longer than after the last previous therapy. All four patients receiving rituximab maintenance were without progression 12 months after RIT-Z. Relapses occurred in both previously and newly involved sites; a significant association was found between the number of pathologic sites involved prior to RIT-Z and subsequent TTNT. Despite the excellent response rate, the duration of response was shorter than the previous one confirming the known trend of relapses to occur earlier after subsequent treatments. Rituximab maintenance after RIT-Z showed encouraging results in terms of prolonging EFS, warranting further studies. Copyright © 2010 John Wiley & Sons, Ltd.

Effects of fou8/fry1 mutation on sulfur metabolism: is decreased internal sulfate the trigger of sulfate starvation response?

The fou8 loss of function allele of adenosine bisphosphate phosphatase FIERY1 results in numerous phenotypes including the increased enzymatic oxygenation of fatty acids and increased jasmonate synthesis. Here we show that the mutation causes also profound alterations of sulfur metabolism. The fou8 mutants possess lower levels of sulfated secondary compounds, glucosinolates, and accumulate the desulfo-precursors similar to previously described mutants in adenosine 5'phosphosulfate kinase. Transcript levels of genes involved in sulfate assimilation differ in fou8 compared to wild type Col-0 plants and are similar to plants subjected to sulfate deficiency. Indeed, independent microarray analyses of various alleles of mutants in FIERY1 showed similar patterns of gene expression as in sulfate deficient plants. This was not caused by alterations in signalling, as the fou8 mutants contained significantly lower levels of sulfate and glutathione and, consequently, of total elemental sulfur. Analysis of mutants with altered levels of sulfate and glutathione confirmed the correlation of sulfate deficiency-like gene expression pattern with low internal sulfate but not low glutathione. The changes in sulfur metabolism in fou8 correlated with massive increases in 3'-phosphoadenosine 5'-phosphate levels. The analysis of fou8 thus revealed that sulfate starvation response is triggered by a decrease in internal sulfate as opposed to external sulfate availability and that the presence of desulfo-glucosinolates does not induce the glucosinolate synthesis network. However, as well as resolving these important questions on the regulation of sulfate assimilation in plants, fou8 has also opened an array of new questions on the links between jasmonate synthesis and sulfur metabolism.

Impact of stressful life event on the global functioning outcome after an assertive community treatment

Background: Assertive community treatment (ACT) was reported to be an effective treatment to improve global functioning of ultra-high risk (UHR) adolescents. However, the infl uence of stressful life event (SLE) was not extensively studied which represent our objective. Method: The SLE (encompassing adoption, migration, family member's deceased, sexual or physical abuse, etc.) of 20 UHR adolescents, treated with an ACT model, were rated. 10 adolescents having 0 to 1 SLE (mainly parents' divorce; low SLE group) were compared 10 adolescents with 2 to 5 SLE (high SLE group). The adolescents were assessed at baseline and after treatment with the Health of Nation Outcome Scale for Children and Adolescents (HoNOSCA). The HoNOSCA allowed rating different diffi culties such as behavior, symptoms, disorders and social. Results: First, results on the whole sample indicated signifi cant improvement after ACT (compared to baseline) on the total (P = .04), symptoms (P = .025) and social (P = .009) scores of the HoNOSCA. Second, the improvement on the HoNOSCA's score of the high SLE group were signifi cantly higher for the total (P = .016), symptoms (P = .019) and behavior (P = .033) scores compared to the low SLE group. Discussion/Conclusion: Globally, ACT seems to be an appropriate treatment to enhance global functioning and more specifi cally the social and symptoms diffi culties of UHR adolescents. Additionally, UHR adolescents with a high numbers of SLE were observed to have a better benefi t of the ACT on global, symptoms and behavioral diffi culties.

Radioimmunotherapy combined with maintenance anti-CD20 antibody may trigger long-term protective T cell immunity in follicular lymphoma patients.

Growing evidence suggests that the patient's immune response may play a major role in the long-term efficacy of antibody therapies of follicular lymphoma (FL). Particular long-lasting recurrence free survivals have been observed after first line, single agent rituximab or after radioimmunotherapy (RIT). Rituximab maintenance, furthermore, has a major efficacy in prolonging recurrence free survival after chemotherapy. On the other hand, RIT as a single step treatment showed a remarkable capacity to induce complete and partial remissions when applied in recurrence and as initial treatment of FL or given for consolidation. These clinical results strongly suggest that RIT combined with rituximab maintenance could stabilize the high percentages of patients with CR and PR induced by RIT. While the precise mechanisms of the long-term efficacy of these 2 treatments are not elucidated, different observations suggest that the patient's T cell immune response could be decisive. With this review, we discuss the potential role of the patient's immune system under rituximab and RIT and argue that the T cell immunity might be particularly promoted when combining the 2 antibody treatments in the early therapy of FL.

Detection of millimetric deformation using a terrestrial laser scanner: experiment and application to a rockfall event

Terrestrial laser scanning (TLS) is one of the most promising surveying techniques for rockslope characterization and monitoring. Landslide and rockfall movements can be detected by means of comparison of sequential scans. One of the most pressing challenges of natural hazards is combined temporal and spatial prediction of rockfall. An outdoor experiment was performed to ascertain whether the TLS instrumental error is small enough to enable detection of precursory displacements of millimetric magnitude. This consists of a known displacement of three objects relative to a stable surface. Results show that millimetric changes cannot be detected by the analysis of the unprocessed datasets. Displacement measurement are improved considerably by applying Nearest Neighbour (NN) averaging, which reduces the error (1¿) up to a factor of 6. This technique was applied to displacements prior to the April 2007 rockfall event at Castellfollit de la Roca, Spain. The maximum precursory displacement measured was 45 mm, approximately 2.5 times the standard deviation of the model comparison, hampering the distinction between actual displacement and instrumental error using conventional methodologies. Encouragingly, the precursory displacement was clearly detected by applying the NN averaging method. These results show that millimetric displacements prior to failure can be detected using TLS.

Stratigraphy of the Cenomanian-Turonian Oceanic Anoxic Event OAE2 in shallow shelf sequences of NE Egypt

Two shallow water late Cenomanian to early Turonian sequences of NE Egypt have been investigated to evaluate the response to OAE2. Age control based on calcareous nannoplankton, planktic foraminifera and ammonite biostratigraphies integrated with delta(13)C stratigraphy is relatively good despite low diversity and sporadic occurrences. Planktic and benthic foraminiferal faunas are characterized by dysoxic, brackish and mesotrophic conditions, as indicated by low species diversity, low oxygen and low salinity tolerant planktic and benthic species, along with oyster-rich limestone layers. In these subtidal to inner neritic environments the OAE2 delta(13)C excursion appears comparable and coeval to that of open marine environments. However, in contrast to open marine environments where anoxic conditions begin after the first delta(13)C peak and end at or near the Cenomanian-Turonian boundary, in shallow coastal environments anoxic conditions do not appear until the early Turonian. This delay in anoxia appears to be related to the sea-level transgression that reached its maximum in the early Turonian, as observed in shallow water sections from Egypt to Morocco. (C) 2011 Elsevier Ltd. All rights reserved.

Histones trigger sterile inflammation by activating the NLRP3 inflammasome.

Sterile cell death mediated inflammation is linked to several pathological disorders and involves danger recognition of intracellular molecules released by necrotic cells that activate different groups of innate pattern recognition receptors. Toll-like receptors directly interact with their extrinsic or intrinsic agonists and induce multiple proinflammatory mediators. In contrast, the NLRP3 inflammasome is rather thought to represent a downstream element integrating various indirect stimuli into proteolytic cleavage of interleukin (IL)-1β and IL-18. Here, we report that histones released from necrotic cells induce IL-1β secretion in an NLRP3-ASC-caspase-1-dependent manner. Genetic deletion of NLRP3 in mice significantly attenuated histone-induced IL-1β production and neutrophil recruitment. Furthermore, necrotic cells induced neutrophil recruitment, which was significantly reduced by histone-neutralizing antibodies or depleting extracellular histones via enzymatic degradation. These results identify cytosolic uptake of necrotic cell-derived histones as a triggering mechanism of sterile inflammation, which involves NLRP3 inflammasome activation and IL-1β secretion via oxidative stress.

Age-related differences on event-related potentials and brain rhythm oscillations during working memory activation.

Previous functional imaging studies have pointed to the compensatory recruitment of cortical circuits in old age in order to counterbalance the loss of neural efficiency and preserve cognitive performance. Recent electroencephalographic (EEG) analyses reported age-related deficits in the amplitude of an early positive-negative working memory (PN(wm)) component as well as changes in working memory (WM)-load related brain oscillations during the successful performance of the n-back task. To explore the age-related differences of EEG activation in the face of increasing WM demands, we assessed the PN(wm) component area, parietal alpha event-related synchronization (ERS) as well as frontal theta ERS in 32 young and 32 elderly healthy individuals who successfully performed a highly WM demanding 3-back task. PN(wm) area increased with higher memory loads (3- and 2-back > 0-back tasks) in younger subjects. Older subjects reached the maximal values for this EEG parameter during the less WM demanding 0-back task. They showed a rapid development of an alpha ERS that reached its maximal amplitude at around 800 ms after stimulus onset. In younger subjects, the late alpha ERS occurred between 1,200 and 2,000 ms and its amplitude was significantly higher compared with elders. Frontal theta ERS culmination peak decreased in a task-independent manner in older compared with younger cases. Only in younger individuals, there was a significant decrease in the phasic frontal theta ERS amplitude in the 2- and 3-back tasks compared with the detection and 0-back tasks. These observations suggest that older adults display a rapid mobilization of their neural generators within the parietal cortex to manage very low demanding WM tasks. Moreover, they are less able to activate frontal theta generators during attentional tasks compared with younger persons.

A synchronous, middle early Aptian age for the demise of the Helvetic Urgonian platform related to the unfolding oceanic anoxic event 1a ("Selli event")

Un âge synchrone (partie moyenne de l'Aptien inférieur) de l'ennoiement de la plate-forme Urgonienne helvétique en relation avec l'événement océanique anoxique 1a ("événement Selli"). - La fin de la plate-forme urgonienne, calibrée par analyse des isotopes stables du carbone sur roche totale et par biostratigraphie basée sur les ammonites, est datée du milieu de l'Aptien inférieur (Près de la limite des zones weissi et deshayesi). Cet arrêt, synchrone dans des coupes représentatives du domaine helvétique alpin, est un événement environemental majeur renregistré en France, en Espagne, au Protugal, en Oman, au Mexique et dans le domaine Pacifique. En tenant compte des limites de résolution de la biostatrigraphie et des autres techniques de datation, cet épisode semble également être synchrone à l'échelle globale. Pour beaucoup d'auteurs, la disparition de récifs de coraux et de rudistes corrélée à la fin de la sédimentation urgonienne correspond à la mise en place de conditions anoxiques à l'Aptien inférieur. Celles-ci caractérisent un événement d'importance global: l'événement anoxique OAE 1a.

Heterogeneity and event dependence in the analysis of sickness absence

Sickness absence (SA) is an important social, economic and public health issue. Identifying and understanding the determinants, whether biological, regulatory or, health services-related, of variability in SA duration is essential for better management of SA. The conditional frailty model (CFM) is useful when repeated SA events occur within the same individual, as it allows simultaneous analysis of event dependence and heterogeneity due to unknown, unmeasured, or unmeasurable factors. However, its use may encounter computational limitations when applied to very large data sets, as may frequently occur in the analysis of SA duration. To overcome the computational issue, we propose a Poisson-based conditional frailty model (CFPM) for repeated SA events that accounts for both event dependence and heterogeneity. To demonstrate the usefulness of the model proposed in the SA duration context, we used data from all non-work-related SA episodes that occurred in Catalonia (Spain) in 2007, initiated by either a diagnosis of neoplasm or mental and behavioral disorders. As expected, the CFPM results were very similar to those of the CFM for both diagnosis groups. The CPU time for the CFPM was substantially shorter than the CFM. The CFPM is an suitable alternative to the CFM in survival analysis with recurrent events,especially with large databases.