Pretransplant HLA typing revealed loss of heterozygosity in the major histocompatibility complex in a patient with acute myeloid leukemia

Introduction Chromosomal abnormalities are frequent events in hematological malignancies. The degree of HLA compatibility between donor and recipient in hematopoietic stem cell transplantation is critical. Purpose of the study In this report, we describe an acute myeloid leukemia case with loss of heterozygosity (LOH) encompassing the entire HLA. Materials and methods HLA molecular typing was performed on peripheral blood (PB) and buccal swabs (BS). Chromosomal microarray analysis (CMA) was performed using a whole genome platform. Results Typing results on PB sample collected during blast crisis demonstrated homozygosity at the -A, -B, -C, -DR, and -DQ loci. A BS sample demonstrated heterozygosity at all loci. A subsequent PB sample drawn after count recovery confirmed heterozygosity. The CMA performed on PB samples collected during and after blast crisis revealed a large terminal region of copy-neutral LOH involving chromosome region 6p25.3p21.31, spanning approximately 35.9 Mb. The results of the CMA assay on sample collected after count recovery did not demonstrate LOH. Conclusions LOH at the HLA gene locus may significantly influence the donor search resulting in mistakenly choosing homozygous donors. We recommend confirming the HLA typing of recipients with hematological malignancies when homozygosity is detected at any locus by using BS samples, or alternatively from PB when remission is achieved

Big data and data repurposing – using existing data to answer new questions in vascular dementia research

Introduction: Traditional approaches to clinical research have, as yet, failed to provide effective treatments for vascular dementia (VaD). Novel approaches to collation and synthesis of data may allow for time and cost efficient hypothesis generating and testing. These approaches may have particular utility in helping us understand and treat a complex condition such as VaD. Methods: We present an overview of new uses for existing data to progress VaD research. The overview is the result of consultation with various stakeholders, focused literature review and learning from the group’s experience of successful approaches to data repurposing. In particular, we benefitted from the expert discussion and input of delegates at the 9th International Congress on Vascular Dementia (Ljubljana, 16-18th October 2015). Results: We agreed on key areas that could be of relevance to VaD research: systematic review of existing studies; individual patient level analyses of existing trials and cohorts and linking electronic health record data to other datasets. We illustrated each theme with a case-study of an existing project that has utilised this approach. Conclusions: There are many opportunities for the VaD research community to make better use of existing data. The volume of potentially available data is increasing and the opportunities for using these resources to progress the VaD research agenda are exciting. Of course, these approaches come with inherent limitations and biases, as bigger datasets are not necessarily better datasets and maintaining rigour and critical analysis will be key to optimising data use

Utility of an attention-based performance validity test for the detection of feigned cognitive dysfunction after acquired brain injury

Introduction: The Groningen Effort Test (GET) is a recently developed performance validity test (PVT) for the identification of noncredible performance in a neuropsychological assessment of attention abilities. Because the majority of already established PVTs are based on memory functions, the GET has the potential to make a valuable contribution to validity testing.Method: The current study examined the utility of the GET in the detection of feigned cognitive dysfunction after acquired brain injury (ABI) and its incremental validity over already established PVTs, namely the Test of Memory Malingering (TOMM), the Dot Counting Test (DCT), and the b Test. Three hundred and forty-eight participants took part in this study, including 58 patients with ABI (stroke or traumatic brain injury), 43 healthy individuals instructed to show normal behavior, and 247 healthy individuals instructed to feign cognitive dysfunction after ABI.Results: With excellent overall classification accuracy, the GET performed close to the level of the TOMM, and superior to the b Test and DCT. Data analyses further revealed that the GET provides additional diagnostic accuracy compared to the b Test and the DCT in the detection of feigned cognitive dysfunction, but has no incremental validity over the TOMM. For each of the four PVTs in this study, diagnostic sensitivity was independent of the simulation strategy used.Conclusions: It is concluded that the GET is an attention-based PVT with promising test characteristics and high diagnostic accuracy in the detection of noncredible cognitive performance using a simulation design. Given the results can be replicated in studies using known-groups methodology, it may be a useful tool for clinical practice to complement neuropsychological assessments of patients with ABI

Supernova PTF12glz: a possible shock breakout driven through an aspherical wind

We present visible-light and ultraviolet (UV) observations of the supernova PTF12glz. The SN was discovered and monitored in near-UV and R bands as part of a joint GALEX and Palomar Transient Factory campaign. It is among the most energetic Type IIn supernovae observed to date (~10^51erg). If the radiated energy mainly came from the thermalization of the shock kinetic energy, we show that PTF12glz was surrounded by ~1 solar mass of circumstellar material (CSM) prior to its explosive death. PTF12glz shows a puzzling peculiarity: at early times, while the freely expanding ejecta are presumably masked by the optically thick CSM, the radius of the blackbody that best fits the observations grows at ~8000km/s. Such a velocity is characteristic of fast moving ejecta rather than optically thick CSM. This phase of radial expansion takes place before any spectroscopic signature of expanding ejecta appears in the spectrum and while both the spectroscopic data and the bolometric luminosity seem to indicate that the CSM is optically thick. We propose a geometrical solution to this puzzle, involving an aspherical structure of the CSM around PTF12glz. By modeling radiative diffusion through a slab of CSM, we show that an aspherical geometry of the CSM can result in a growing effective radius. This simple model also allows us to recover the decreasing blackbody temperature of PTF12glz. SLAB-Diffusion, the code we wrote to model the radiative diffusion of photons through a slab of CSM and evaluate the observed radius and temperature, is made available on-line.Comment: Sumbitted to ApJ. Comments are welcom

SPICES: Spectro-Polarimetric Imaging and Characterization of Exoplanetary Systems

SPICES (Spectro-Polarimetric Imaging and Characterization of Exoplanetary Systems) is a five-year M-class mission proposed to ESA Cosmic Vision. Its purpose is to image and characterize long-period extrasolar planets and circumstellar disks in the visible (450 - 900 nm) at a spectral resolution of about 40 using both spectroscopy and polarimetry. By 2020/22, present and near-term instruments will have found several tens of planets that SPICES will be able to observe and study in detail. Equipped with a 1.5 m telescope, SPICES can preferentially access exoplanets located at several AUs (0.5-10 AU) from nearby stars ($<$25 pc) with masses ranging from a few Jupiter masses to Super Earths ($\sim$2 Earth radii, $\sim$10 M$_{\oplus}$) as well as circumstellar disks as faint as a few times the zodiacal light in the Solar System

A Two-Dimensional Electron Gas as a Sensitive Detector for Time-Resolved Tunneling Measurements on Self-Assembled Quantum Dots

A two-dimensional electron gas (2DEG) situated nearby a single layer of self-assembled quantum dots (QDs) in an inverted high electron mobility transistor (HEMT) structure is used as a detector for time-resolved tunneling measurements. We demonstrate a strong influence of charged QDs on the conductance of the 2DEG which allows us to probe the tunneling dynamics between the 2DEG and the QDs time resolved. Measurements of hysteresis curves with different sweep times and real-time conductance measurements in combination with an boxcar-like evaluation method enables us to unambiguously identify the transients as tunneling events between the s- and p-electron QD states and the 2DEG and rule out defect-related transients

Text mining for biology - the way forward: opinions from leading scientists

This article collects opinions from leading scientists about how text mining can provide better access to the biological literature, how the scientific community can help with this process, what the next steps are, and what role future BioCreative evaluations can play. The responses identify several broad themes, including the possibility of fusing literature and biological databases through text mining; the need for user interfaces tailored to different classes of users and supporting community-based annotation; the importance of scaling text mining technology and inserting it into larger workflows; and suggestions for additional challenge evaluations, new applications, and additional resources needed to make progress

Comparison of Pittsburgh compound B and florbetapir in cross-sectional and longitudinal studies.

IntroductionQuantitative in vivo measurement of brain amyloid burden is important for both research and clinical purposes. However, the existence of multiple imaging tracers presents challenges to the interpretation of such measurements. This study presents a direct comparison of Pittsburgh compound B-based and florbetapir-based amyloid imaging in the same participants from two independent cohorts using a crossover design.MethodsPittsburgh compound B and florbetapir amyloid PET imaging data from three different cohorts were analyzed using previously established pipelines to obtain global amyloid burden measurements. These measurements were converted to the Centiloid scale to allow fair comparison between the two tracers. The mean and inter-individual variability of the two tracers were compared using multivariate linear models both cross-sectionally and longitudinally.ResultsGlobal amyloid burden measured using the two tracers were strongly correlated in both cohorts. However, higher variability was observed when florbetapir was used as the imaging tracer. The variability may be partially caused by white matter signal as partial volume correction reduces the variability and improves the correlations between the two tracers. Amyloid burden measured using both tracers was found to be in association with clinical and psychometric measurements. Longitudinal comparison of the two tracers was also performed in similar but separate cohorts whose baseline amyloid load was considered elevated (i.e., amyloid positive). No significant difference was detected in the average annualized rate of change measurements made with these two tracers.DiscussionAlthough the amyloid burden measurements were quite similar using these two tracers as expected, difference was observable even after conversion into the Centiloid scale. Further investigation is warranted to identify optimal strategies to harmonize amyloid imaging data acquired using different tracers

Measurement of the Lifetime Difference Between B_s Mass Eigenstates

We present measurements of the lifetimes and polarization amplitudes for B_s --> J/psi phi and B_d --> J/psi K*0 decays. Lifetimes of the heavy (H) and light (L) mass eigenstates in the B_s system are separately measured for the first time by determining the relative contributions of amplitudes with definite CP as a function of the decay time. Using 203 +/- 15 B_s decays, we obtain tau_L = (1.05 +{0.16}/-{0.13} +/- 0.02) ps and tau_H = (2.07 +{0.58}/-{0.46} +/- 0.03) ps. Expressed in terms of the difference DeltaGamma_s and average Gamma_s, of the decay rates of the two eigenstates, the results are DeltaGamma_s/Gamma_s = (65 +{25}/-{33} +/- 1)%, and DeltaGamma_s = (0.47 +{0.19}/-{0.24} +/- 0.01) inverse ps.Comment: 8 pages, 3 figures, 2 tables; as published in Physical Review Letters on 16 March 2005; revisions are for length and typesetting only, no changes in results or conclusion

Cardiovascular Agents Affect the Tone of Pulmonary Arteries and Veins in Precision-Cut Lung Slices

Cardiovascular agents are pivotal in the therapy of heart failure. Apart from their action on ventricular contractility and systemic afterload, they affect pulmonary arteries and veins. Although these effects are crucial in heart failure with coexisting pulmonary hypertension or lung oedema, they are poorly defined, especially in pulmonary veins. Therefore, we investigated the pulmonary vascular effects of adrenoceptor agonists, vasopressin and angiotensin II in the model of precision-cut lung slices that allows simultaneous studies of pulmonary arteries and veins.Precision-cut lung slices were prepared from guinea pigs and imaged by videomicroscopy. Concentration-response curves of cardiovascular drugs were analysed in pulmonary arteries and veins.Pulmonary veins responded stronger than arteries to α(1)-agonists (contraction) and β(2)-agonists (relaxation). Notably, inhibition of β(2)-adrenoceptors unmasked the α(1)-mimetic effect of norepinephrine and epinephrine in pulmonary veins. Vasopressin and angiotensin II contracted pulmonary veins via V(1a) and AT(1) receptors, respectively, without affecting pulmonary arteries.Vasopressin and (nor)epinephrine in combination with β(2)-inhibition caused pulmonary venoconstriction. If applicable in humans, these treatments would enhance capillary hydrostatic pressures and lung oedema, suggesting their cautious use in left heart failure. Vice versa, the prevention of pulmonary venoconstriction by AT(1) receptor antagonists might contribute to their beneficial effects seen in left heart failure. Further, α(1)-mimetic agents might exacerbate pulmonary hypertension and right ventricular failure by contracting pulmonary arteries, whereas vasopressin might not