Establishing optimal quantitative-polymerase chain reaction assays for routine diagnosis and tracking of minimal residual disease in JAK2-V617F-associated myeloproliferative neoplasms:a joint European LeukemiaNet/MPN&MPNr-EuroNet (COST action BM0902) study

Reliable detection of JAK2-V617F is critical for accurate diagnosis of myeloproliferative neoplasms (MPNs); in addition, sensitive mutation-specific assays can be applied to monitor disease response. However, there has been no consistent approach to JAK2-V617F detection, with assays varying markedly in performance, affecting clinical utility. Therefore, we established a network of 12 laboratories from seven countries to systematically evaluate nine different DNA-based quantitative PCR (qPCR) assays, including those in widespread clinical use. Seven quality control rounds involving over 21,500 qPCR reactions were undertaken using centrally distributed cell line dilutions and plasmid controls. The two best-performing assays were tested on normal blood samples (n=100) to evaluate assay specificity, followed by analysis of serial samples from 28 patients transplanted for JAK2-V617F-positive disease. The most sensitive assay, which performed consistently across a range of qPCR platforms, predicted outcome following transplant, with the mutant allele detected a median of 22 weeks (range 6-85 weeks) before relapse. Four of seven patients achieved molecular remission following donor lymphocyte infusion, indicative of a graft vs MPN effect. This study has established a robust, reliable assay for sensitive JAK2-V617F detection, suitable for assessing response in clinical trials, predicting outcome and guiding management of patients undergoing allogeneic transplant.

On the MIMO Capacity with Residual Transceiver Hardware Impairments

Radio-frequency (RF) impairments in the transceiver hardware of communication systems (e.g., phase noise (PN), high power amplifier (HPA) nonlinearities, or in-phase/quadrature-phase (I/Q) imbalance) can severely degrade the performance of traditional multiple-input multiple-output (MIMO) systems. Although calibration algorithms can partially compensate these impairments, the remaining distortion still has substantial impact. Despite this, most prior works have not analyzed this type of distortion. In this paper, we investigate the impact of residual transceiver hardware impairments on the MIMO system performance. In particular, we consider a transceiver impairment model, which has been experimentally validated, and derive analytical ergodic capacity expressions for both exact and high signal-to-noise ratios (SNRs). We demonstrate that the capacity saturates in the high-SNR regime, thereby creating a finite capacity ceiling. We also present a linear approximation for the ergodic capacity in the low-SNR regime, and show that impairments have only a second-order impact on the capacity. Furthermore, we analyze the effect of transceiver impairments on large-scale MIMO systems; interestingly, we prove that if one increases the number of antennas at one side only, the capacity behaves similar to the finite-dimensional case. On the contrary, if the number of antennas on both sides increases with a fixed ratio, the capacity ceiling vanishes; thus, impairments cause only a bounded offset in the capacity compared to the ideal transceiver hardware case.

Impact of Residual Transmit RF Impairments on Training-Based MIMO Systems

Radio-frequency (RF) impairments, which intimately exist in wireless communication systems, can severely limit the performance of multiple-input-multiple-output (MIMO) systems. Although we can resort to compensation schemes to mitigate some of these impairments, a certain amount of residual impairments always persists. In this paper, we consider a training-based point-to-point MIMO system with residual transmit RF impairments (RTRI) using spatial multiplexing transmission. Specifically, we derive a new linear channel estimator for the proposed model, and show that RTRI create an estimation error floor in the high signal-to-noise ratio (SNR) regime. Moreover, we derive closed-form expressions for the signal-to-noise-plus-interference ratio (SINR) distributions, along with analytical expressions for the ergodic achievable rates of zero-forcing, maximum ratio combining, and minimum mean-squared error receivers, respectively. In addition, we optimize the ergodic achievable rates with respect to the training sequence length and demonstrate that finite dimensional systems with RTRI generally require more training at high SNRs than those with ideal hardware. Finally, we extend our analysis to large-scale MIMO configurations, and derive deterministic equivalents of the ergodic achievable rates. It is shown that, by deploying large receive antenna arrays, the extra training requirements due to RTRI can be eliminated. In fact, with a sufficiently large number of receive antennas, systems with RTRI may even need less training than systems with ideal hardware.

Minimal residual disease detection in childhood acute lymphoblastic leukaemia patients at multiple time-points reveals high levels of concordance between molecular and immunophenotypic approaches

In this single centre study of childhood acute lymphoblastic leukaemia (ALL) patients treated on the Medical Research Council UKALL 97/99 protocols, it was determined that minimal residual disease (MRD) detected by real time quantitative polymerase chain reaction (RQ-PCR) and 3-colour flow cytometry (FC) displayed high levels of qualitative concordance when evaluated at multiple time-points during treatment (93.38%), and a combined use of both approaches allowed a multi time-point evaluation of MRD kinetics for 90% (53/59) of the initial cohort. At diagnosis, MRD markers with sensitivity of at least 0.01% were identified by RQ-PCR detection of fusion gene transcripts, IGH/TRG rearrangements, and FC. Using a combined RQ-PCR and FC approach, the evaluation of 367 follow-up BM samples revealed that the detection of MRD >1% at Day 15 (P = 0.04), >0.01% at the end of induction (P = 0.02), >0.01% at the end of consolidation (P = 0.01), >0.01% prior to the first delayed intensification (P = 0.01), and >0.1% prior to the second delayed intensification and continued maintenance (P = 0.001) were all associated with relapse and, based on early time-points (end of induction and consolidation) a significant log-rank trend (P = 0.0091) was noted between survival curves for patients stratified into high, intermediate and low-risk MRD groups.

Wilms' tumor gene 1 (WT1) expression in childhood acute lymphoblastic leukemia:a wide range of WT1 expression levels, its impact on prognosis and minimal residual disease monitoring

Wilms' tumor gene 1 (WT1) is overexpressed in the majority (70-90%) of acute leukemias and has been identified as an independent adverse prognostic factor, a convenient minimal residual disease (MRD) marker and potential therapeutic target in acute leukemia. We examined WT1 expression patterns in childhood acute lymphoblastic leukemia (ALL), where its clinical implication remains unclear. Using a real-time quantitative PCR designed according to Europe Against Cancer Program recommendations, we evaluated WT1 expression in 125 consecutively enrolled patients with childhood ALL (106 BCP-ALL, 19 T-ALL) and compared it with physiologic WT1 expression in normal and regenerating bone marrow (BM). In childhood B-cell precursor (BCP)-ALL, we detected a wide range of WT1 levels (5 logs) with a median WT1 expression close to that of normal BM. WT1 expression in childhood T-ALL was significantly higher than in BCP-ALL (P<0.001). Patients with MLL-AF4 translocation showed high WT1 overexpression (P<0.01) compared to patients with other or no chromosomal aberrations. Older children (> or =10 years) expressed higher WT1 levels than children under 10 years of age (P<0.001), while there was no difference in WT1 expression in patients with peripheral blood leukocyte count (WBC) > or =50 x 10(9)/l and lower. Analysis of relapsed cases (14/125) indicated that an abnormal increase or decrease in WT1 expression was associated with a significantly increased risk of relapse (P=0.0006), and this prognostic impact of WT1 was independent of other main risk factors (P=0.0012). In summary, our study suggests that WT1 expression in childhood ALL is very variable and much lower than in AML or adult ALL. WT1, thus, will not be a useful marker for MRD detection in childhood ALL, however, it does represent a potential independent risk factor in childhood ALL. Interestingly, a proportion of childhood ALL patients express WT1 at levels below the normal physiological BM WT1 expression, and this reduced WT1 expression appears to be associated with a higher risk of relapse.

Chimaerism following allogeneic bone marrow transplantation:detection of residual host cells using the polymerase chain reaction

Chimaerism was assessed in five recipients following sex mismatched allogeneic bone marrow transplantation. Techniques included karyotyping of bone marrow cells, dot blot DNA analysis of blood and bone marrow suspensions, and in vitro amplification of DNA by the polymerase chain reaction (PCR) using blood and bone marrow suspensions and stored bone marrow slides. Results of karyotypic analysis suggested complete chimaerism in four patients, while in one patient mixed chimaerism was detected. Mixed chimaerism was also detected, however, in a second patient using PCR and confirmed by dot blot analysis on all tissues examined. PCR is a sensitive tool for investigation of chimaerism following bone marrow transplantation. Since this technique does not require radioactivity, it is an attractive method for use in a clinical laboratory. This technique represents a further development in the use of DNA methodologies in the assessment of haematological disease.

Predicting impact damage, residual strength and crashworthiness of composite structures

The development of the latest generation of wide-body carbon-fibre composite passenger aircraft has heralded a new era in the utilisation of these materials. The premise of superior specific strength and stiffness, corrosion and fatigue resistance, is tempered by high development costs, slow production rates and lengthy and expensive certification programmes. Substantial effort is currently being directed towards the development of new modelling and simulation tools, at all levels of the development cycle, to mitigate these shortcomings. One of the primary challenges is to reduce the extent of physical testing, in the certification process, by adopting a ‘certification by simulation’ approach. In essence, this aspirational objective requires the ability to reliably predict the evolution and progression of damage in composites. The aerospace industry has been at the forefront of developing advanced composites modelling tools. As the automotive industry transitions towards the increased use of composites in mass-produced vehicles, similar challenges in the modelling of composites will need to be addressed, particularly in the reliable prediction of crashworthiness. While thermoset composites have dominated the aerospace industry, thermoplastics composites are likely to emerge as the preferred solution for meeting the high-volume production demands of passenger road vehicles. This keynote presentation will outline recent progress and current challenges in the development of finite-element-based predictive modelling tools for capturing impact damage, residual strength and energy absorption capacity of thermoset and thermoplastic composites for crashworthiness assessments.

NMR in the characterization of heavy residual procedural streams

The main objective of this work was to monitor a set of physical-chemical properties of heavy oil procedural streams through nuclear magnetic resonance spectroscopy, in order to propose an analysis procedure and online data processing for process control. Different statistical methods which allow to relate the results obtained by nuclear magnetic resonance spectroscopy with the results obtained by the conventional standard methods during the characterization of the different streams, have been implemented in order to develop models for predicting these same properties. The real-time knowledge of these physical-chemical properties of petroleum fractions is very important for enhancing refinery operations, ensuring technically, economically and environmentally proper refinery operations. The first part of this work involved the determination of many physical-chemical properties, at Matosinhos refinery, by following some standard methods important to evaluate and characterize light vacuum gas oil, heavy vacuum gas oil and fuel oil fractions. Kinematic viscosity, density, sulfur content, flash point, carbon residue, P-value and atmospheric and vacuum distillations were the properties analysed. Besides the analysis by using the standard methods, the same samples were analysed by nuclear magnetic resonance spectroscopy. The second part of this work was related to the application of multivariate statistical methods, which correlate the physical-chemical properties with the quantitative information acquired by nuclear magnetic resonance spectroscopy. Several methods were applied, including principal component analysis, principal component regression, partial least squares and artificial neural networks. Principal component analysis was used to reduce the number of predictive variables and to transform them into new variables, the principal components. These principal components were used as inputs of the principal component regression and artificial neural networks models. For the partial least squares model, the original data was used as input. Taking into account the performance of the develop models, by analysing selected statistical performance indexes, it was possible to conclude that principal component regression lead to worse performances. When applying the partial least squares and artificial neural networks models better results were achieved. However, it was with the artificial neural networks model that better predictions were obtained for almost of the properties analysed. With reference to the results obtained, it was possible to conclude that nuclear magnetic resonance spectroscopy combined with multivariate statistical methods can be used to predict physical-chemical properties of petroleum fractions. It has been shown that this technique can be considered a potential alternative to the conventional standard methods having obtained very promising results.

Avaliaçao do potencial energético da biomassa florestal residual na ZIF de Arade-Alte/ São Bartolomeu de Messines

Dissertação de mest., Energias Renováveis e Gestão de Energia, Faculdade de Ciências e Tecnologia, Univ. do Algarve, 2011

Assessing residual reasoning ability in overtly non-communicative patients using fMRI

It is now well established that some patients who are diagnosed as being in a vegetative state or a minimally conscious state show reliable signs of volition that may only be detected by measuring neural responses. A pertinent question is whether these patients are also capable of logical thought. Here, we validate an fMRI paradigm that can detect the neural fingerprint of reasoning processes and moreover, can confirm whether a participant derives logical answers. We demonstrate the efficacy of this approach in a physically non-communicative patient who had been shown to engage in mental imagery in response to simple audi- tory instructions. Our results demonstrate that this individual retains a remarkable capacity for higher cogni- tion, engaging in the reasoning task and deducing logical answers. We suggest that this approach is suitable for detecting residual reasoning ability using neural responses and could readily be adapted to assess other aspects of cognition.

Avaliação e correlação de parâmetros físicos e mecânicos de um solo residual granítico

Os solos residuais mostram divergências em relação aos solos transportados modelados pelas teorias da Mecânica dos Solos. Estas divergências são em grande parte devido a uma estrutura de cimentação herdada da rocha mãe. Este estudo foi baseado nos resultados obtidos em sondagens mecânicas e ensaios de penetração dinâmica, estática e laboratoriais e consistiu na avaliação e correlação dos parâmetros que determinam o comportamento geomecânico do terreno, como a resistência e a deformabilidade.