High-dose therapy and autologous hematopoietic stem cell transplant in T-cell lymphoma: a single center experience.

Abstract We report here the long-term outcome of autologous stem cell transplant in peripheral T-cell lymphoma (PTCL). Forty-three consecutive patients with PTCL diagnosed between 2000 and 2011 were treated with high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT) in our center. Diagnoses included PTCL-not otherwise specified (n = 19), anaplastic large cell lymphoma (n = 11), angioimmunoblastic T-cell lymphoma (n = 5), enteropathy-associated T-cell lymphoma (n = 5) and other rare subtypes (n = 3). Thirty-six patients with a median age of 50 years (range 22-65) were transplanted in first response and seven after relapse. After a median follow-up of 63 months, estimated overall survival at 12 years was 40%, progression-free survival at 12 years was 34% and event-free survival at 12 years was 30%. On univariate analysis, age less than 50 years and no B symptoms at diagnosis were significantly associated with prolonged overall and progression-free-survival. HDCT/ASCT for peripheral T-cell lymphoma can lead to long-term survival for patients responding to induction chemotherapy.

Comparing ICA-based and single-trial topographic ERP analyses.

Single-trial analysis of human electroencephalography (EEG) has been recently proposed for better understanding the contribution of individual subjects to a group-analysis effect as well as for investigating single-subject mechanisms. Independent Component Analysis (ICA) has been repeatedly applied to concatenated single-trial responses and at a single-subject level in order to extract those components that resemble activities of interest. More recently we have proposed a single-trial method based on topographic maps that determines which voltage configurations are reliably observed at the event-related potential (ERP) level taking advantage of repetitions across trials. Here, we investigated the correspondence between the maps obtained by ICA versus the topographies that we obtained by the single-trial clustering algorithm that best explained the variance of the ERP. To do this, we used exemplar data provided from the EEGLAB website that are based on a dataset from a visual target detection task. We show there to be robust correspondence both at the level of the activation time courses and at the level of voltage configurations of a subset of relevant maps. We additionally show the estimated inverse solution (based on low-resolution electromagnetic tomography) of two corresponding maps occurring at approximately 300 ms post-stimulus onset, as estimated by the two aforementioned approaches. The spatial distribution of the estimated sources significantly correlated and had in common a right parietal activation within Brodmann's Area (BA) 40. Despite their differences in terms of theoretical bases, the consistency between the results of these two approaches shows that their underlying assumptions are indeed compatible.

The role of auditory cortices in the retrieval of single-trial auditory-visual object memories.

Single-trial encounters with multisensory stimuli affect both memory performance and early-latency brain responses to visual stimuli. Whether and how auditory cortices support memory processes based on single-trial multisensory learning is unknown and may differ qualitatively and quantitatively from comparable processes within visual cortices due to purported differences in memory capacities across the senses. We recorded event-related potentials (ERPs) as healthy adults (n = 18) performed a continuous recognition task in the auditory modality, discriminating initial (new) from repeated (old) sounds of environmental objects. Initial presentations were either unisensory or multisensory; the latter entailed synchronous presentation of a semantically congruent or a meaningless image. Repeated presentations were exclusively auditory, thus differing only according to the context in which the sound was initially encountered. Discrimination abilities (indexed by d') were increased for repeated sounds that were initially encountered with a semantically congruent image versus sounds initially encountered with either a meaningless or no image. Analyses of ERPs within an electrical neuroimaging framework revealed that early stages of auditory processing of repeated sounds were affected by prior single-trial multisensory contexts. These effects followed from significantly reduced activity within a distributed network, including the right superior temporal cortex, suggesting an inverse relationship between brain activity and behavioural outcome on this task. The present findings demonstrate how auditory cortices contribute to long-term effects of multisensory experiences on auditory object discrimination. We propose a new framework for the efficacy of multisensory processes to impact both current multisensory stimulus processing and unisensory discrimination abilities later in time.

Use of GRADE for assessment of evidence about prognosis : rating confidence in estimates of event rates in broad categories of patients.

Main concepts : The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach defines quality of evidence as confidence in effect estimates; this conceptualization can readily be applied to bodies of evidence estimating the risk of future of events (that is, prognosis) in broadly defined populations In the field of prognosis, a body of observational evidence (including single arms of randomized controlled trials) begins as high quality evidence. The five domains GRADE considers in rating down confidence in estimates of treatment effect-that is, risk of bias, imprecision, inconsistency, indirectness, and publication bias-as well as the GRADE criteria for rating up quality, also apply to estimates of the risk of future of events from a body of prognostic studies Applying these concepts to systematic reviews of prognostic studies provides a ful approach to determine confidence in estimates of overall prognosis in broad populations.

Quantifying the time for accurate EEG decoding of single value-based decisions.

BACKGROUND: Recent neuroimaging studies suggest that value-based decision-making may rely on mechanisms of evidence accumulation. However no studies have explicitly investigated the time when single decisions are taken based on such an accumulation process. NEW METHOD: Here, we outline a novel electroencephalography (EEG) decoding technique which is based on accumulating the probability of appearance of prototypical voltage topographies and can be used for predicting subjects' decisions. We use this approach for studying the time-course of single decisions, during a task where subjects were asked to compare reward vs. loss points for accepting or rejecting offers. RESULTS: We show that based on this new method, we can accurately decode decisions for the majority of the subjects. The typical time-period for accurate decoding was modulated by task difficulty on a trial-by-trial basis. Typical latencies of when decisions are made were detected at ∼500ms for 'easy' vs. ∼700ms for 'hard' decisions, well before subjects' response (∼340ms). Importantly, this decision time correlated with the drift rates of a diffusion model, evaluated independently at the behavioral level. COMPARISON WITH EXISTING METHOD(S): We compare the performance of our algorithm with logistic regression and support vector machine and show that we obtain significant results for a higher number of subjects than with these two approaches. We also carry out analyses at the average event-related potential level, for comparison with previous studies on decision-making. CONCLUSIONS: We present a novel approach for studying the timing of value-based decision-making, by accumulating patterns of topographic EEG activity at single-trial level.

The dynamics of interfaces: Seven authors in search of encounters across levels of description of an event involving a mother, father, and baby

The interfaces between the intrapsychic, interactional, and intergenerational domains are a new frontier. As a pilot, we exposed ourselves to a complex but controllable situation as viewed by people whose main interest is in one of the three interfaces; we also fully integrated the subjects in the team, to learn about their subjective perspectives and to provide them with an enriching experience. We started with a brief "triadification" sequence (i.e., moving from a "two plus one" to a "three together" family organization). Considering this sequence as representing at a micro level many larger family transitions, we proceeded with a microanalytic interview, a psychodynamic investigation, and a family interview. As expected, larger patterns of correspondences are emerging. Central questions under debate are: What are the most appropriate units at each level of description and what are their articulations between these levels? What is the status of "triadification"? Les interfaces entre les domaines intrapsychiques, interactionnels et intergénérationnels représentent une nouvelle frontiére. A titre exploratoire, nous nous sommes exposés à une situation complexe mais contrǒlable ainsi que le voient ceux dont I'intérět principal se porte sur l'une de ces trois interfaces. Nous avons aussi entièrement intégré les sujets dans l'équipe, de facon à comprendre leur perspective subjective et à leur offrir une expérience enrichissante. Nous avons commencé avec une brève séquence de "triadification," c'est-à-dire passer d'une organisation familiale "deux plus un" à Ltne organisation familiale "trois (add sentenc)ensemble." Considérant cette séquence comme representative à un niveau microscopique de transitions familiales bien plus larges, nous avons procedé à l'entretien microanalytique, à une enquěte psychodynamique et à un entretien familial. Comme prévu, de grands patterns de correspondances émergent. Les questions essentielles sur lesquelles portent le débat sont: quelles les unités les plus appropiées à chaque niveau de description et quelles sont les articulations entre ces niveaux? Quel est le statut de la "triadification"?

Effect of single nucleotide polymorphisms in cytochrome P450 isoenzyme and N-acetyltransferase 2 genes on the metabolism of artemisinin-based combination therapies in malaria patients from Cambodia and Tanzania.

The pharmacogenetics of antimalarial agents are poorly known, although the application of pharmacogenetics might be critical in optimizing treatment. This population pharmacokinetic-pharmacogenetic study aimed at assessing the effects of single nucleotide polymorphisms (SNPs) in cytochrome P450 isoenzyme genes (CYP, namely, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5) and the N-acetyltransferase 2 gene (NAT2) on the pharmacokinetics of artemisinin-based combination therapies in 150 Tanzanian patients treated with artemether-lumefantrine, 64 Cambodian patients treated with artesunate-mefloquine, and 61 Cambodian patients treated with dihydroartemisinin-piperaquine. The frequency of SNPs varied with the enzyme and the population. Higher frequencies of mutant alleles were found in Cambodians than Tanzanians for CYP2C9*3, CYP2D6*10 (100C → T), CYP3A5*3, NAT2*6, and NAT2*7. In contrast, higher frequencies of mutant alleles were found in Tanzanians for CYP2D6*17 (1023C → T and 2850C → T), CYP3A4*1B, NAT2*5, and NAT2*14. For 8 SNPs, no significant differences in frequencies were observed. In the genetic-based population pharmacokinetic analyses, none of the SNPs improved model fit. This suggests that pharmacogenetic data need not be included in appropriate first-line treatments with the current artemisinin derivatives and quinolines for uncomplicated malaria in specific populations. However, it cannot be ruled out that our results represent isolated findings, and therefore more studies in different populations, ideally with the same artemisinin-based combination therapies, are needed to evaluate the influence of pharmacogenetic factors on the clearance of antimalarials.

Single-cell gene-expression profiling reveals qualitatively distinct CD8 T cells elicited by different gene-based vaccines.

CD8 T cells play a key role in mediating protective immunity against selected pathogens after vaccination. Understanding the mechanism of this protection is dependent upon definition of the heterogeneity and complexity of cellular immune responses generated by different vaccines. Here, we identify previously unrecognized subsets of CD8 T cells based upon analysis of gene-expression patterns within single cells and show that they are differentially induced by different vaccines. Three prime-boost vector combinations encoding HIV Env stimulated antigen-specific CD8 T-cell populations of similar magnitude, phenotype, and functionality. Remarkably, however, analysis of single-cell gene-expression profiles enabled discrimination of a majority of central memory (CM) and effector memory (EM) CD8 T cells elicited by the three vaccines. Subsets of T cells could be defined based on their expression of Eomes, Cxcr3, and Ccr7, or Klrk1, Klrg1, and Ccr5 in CM and EM cells, respectively. Of CM cells elicited by DNA prime-recombinant adenoviral (rAd) boost vectors, 67% were Eomes(-) Ccr7(+) Cxcr3(-), in contrast to only 7% and 2% stimulated by rAd5-rAd5 or rAd-LCMV, respectively. Of EM cells elicited by DNA-rAd, 74% were Klrk1(-) Klrg1(-)Ccr5(-) compared with only 26% and 20% for rAd5-rAd5 or rAd5-LCMV. Definition by single-cell gene profiling of specific CM and EM CD8 T-cell subsets that are differentially induced by different gene-based vaccines will facilitate the design and evaluation of vaccines, as well as enable our understanding of mechanisms of protective immunity.

The role of the right parietal cortex in sound localization: a chronometric single pulse transcranial magnetic stimulation study.

Auditory spatial functions, including the ability to discriminate between the positions of nearby sound sources, are subserved by a large temporo-parieto-frontal network. With the aim of determining whether and when the parietal contribution is critical for auditory spatial discrimination, we applied single pulse transcranial magnetic stimulation on the right parietal cortex 20, 80, 90 and 150 ms post-stimulus onset while participants completed a two-alternative forced choice auditory spatial discrimination task in the left or right hemispace. Our results reveal that transient TMS disruption of right parietal activity impairs spatial discrimination when applied at 20 ms post-stimulus onset for sounds presented in the left (controlateral) hemispace and at 80 ms for sounds presented in the right hemispace. We interpret our finding in terms of a critical role for controlateral temporo-parietal cortices over initial stages of the building-up of auditory spatial representation and for a right hemispheric specialization in integrating the whole auditory space over subsequent, higher-order processing stages.

Consequences of the multipatient use of a single-patient capillary blood sampling device (CBSD)

Introduction/objectives: Multipatient use of a single-patient CBSD occurred inan outpatient clinic during 4 to 16 months before itsnotification. We looked for transmission of blood-bornepathogens among exposed patients.Methods: Exposed patients underwent serology testing for HBV,HCV and HIV. Patients with isolated anti-HBc receivedone dose of hepatitis B vaccine to look for a memoryimmune response. Possible transmissions were investigatedby mapping visits and sequencing of the viral genomeif needed.Results: Of 280 exposed patients, 9 had died without suspicionof blood-borne infection, 3 could not be tested, and 5declined investigations. Among the 263 (93%) testedpatients, 218 (83%) had negative results. We confirmeda known history of HCV infection in 6 patients (1 coinfectedby HIV), and also identified resolved HBVinfection in 37 patients, of whom 18 were alreadyknown. 2 patients were found to have a previouslyunknown HCV infection. According to the time elapsedfrom the closest previous visit of a HCV-infected potentialsource patient, we could rule out nosocomial transmissionin one case (14 weeks) but not in the other (1day). In the latter, however, transmission was deemedvery unlikely by 2 reference centers based on thesequences of the E1 and HVR1 regions of the virus.Conclusion: We did not identify any transmission of blood-bornepathogens in 263 patients exposed to a single-patientCBSD, despite the presence of potential source cases.Change of needle and disinfection of the device betweenpatients may have contributed to this outcome.Although we cannot exclude transmission of HBV, previousacquisition in endemic countries is a more likelyexplanation in this multi-national population.

In situ evaluation of single-cell lysis by cytosol extraction observation through fluorescence decay and dielectrophoretic trapping time

We present a new method for lysis of single cells in continuous flow, where cells are sequentially trapped, lysed and released in an automatic process. Using optimized frequencies, dielectrophoretic trapping allows exposing cells in a reproducible way to high electrical fields for long durations, thereby giving good control on the lysis parameters. In situ evaluation of cytosol extraction on single cells has been studied for Chinese hamster ovary (CHO) cells through out-diffusion of fluorescent molecules for different voltage amplitudes. A diffusion model is proposed to correlate this out-diffusion to the total area of the created pores, which is dependent on the potential drop across the cell membrane and enables evaluation of the total pore area in the membrane. The dielectrophoretic trapping is no longer effective after lysis because of the reduced conductivity inside the cells, leading to cell release. The trapping time is linked to the time required for cytosol extraction and can thus provide additional validation of the effective cytosol extraction for non-fluorescent cells. Furthermore, the application of one single voltage for both trapping and lysis provides a fully automatic process including cell trapping, lysis, and release, allowing operating the device in continuous flow without human intervention.