Comparison of Chimerism and Minimal Residual Disease Monitoring for Relapse Prediction after Allogeneic Stem Cell Transplantation for Adult Acute Lymphoblastic Leukemia

AbstractLittle data are available on the relative merits of chimerism and minimal residual disease (MRD) monitoring for relapse prediction after allogeneic hematopoietic stem cell transplantation (HCT). We performed a retrospective analysis of serial chimerism assessments in 101 adult HCT recipients with acute lymphoblastic leukemia (ALL) and of serial MRD assessments in a subgroup of 22 patients. All patients had received myeloablative conditioning. The cumulative incidence of relapse was significantly higher in the patients with increasing mixed chimerism (in-MC) compared with those with complete chimerism, low-level MC, and decreasing MC, but the sensitivity of in-MC detection with regard to relapse prediction was only modest. In contrast, MRD assessment was highly sensitive and specific. Patients with MRD positivity after HCT had the highest incidence of relapse among all prognostic groups analyzed. The median time from MRD positivity to relapse was longer than the median time from detection of in-MC, but in some cases in-MC preceded MRD positivity. We conclude that MRD assessment is a powerful prognostic tool that should be included in the routine post-transplantation monitoring of patients with ALL, but chimerism analysis may provide additional information in some cases. Integration of these tools and clinical judgment should allow optimal decision making with regard to post-transplantation therapeutic interventions

Effects of clinical decision topic on patients’ involvement in and satisfaction with decisions and their subsequent implementation

Clinical decision-making is the vehicle for mental health care delivery, and predictors of decision-making experience and adherence are under-researched. The aim was to investigate the relationship between decision topic and kind of involvement in the decision, satisfaction and subsequent implementation, from both staff and patient perspectives

A novel TaulacZ allele reveals a requirement for Pitx2 in formation of the mammillothalamic tract

The hypothalamic mammillary region is critical for spatial memory and vestibular processing. Pitx2 encodes a paired‐like transcription factor that is highly expressed in the developing mammillary region and is required for subthalamic nucleus formation. Here we analyzed a loss of function Pitx2 ‐ TaulacZ knock‐in allele to study the effects of Pitx2 deficiency on neuronal projections in the embryonic mammillary region. Pitx2 ‐expressing neurons contribute axons to principal mammillary, mammillotegmental and mammillotectal tracts. Embryos with Pitx2 deficiency exhibit axonal fibers in the principal mammillary tract that are improperly bundled and disorganized, yet project caudally toward the tectum and tegmentum. Embryos with Nestin‐Cre mediated conditional Pitx2 deficiency exhibit truncated mammillothalamic tracts (mtt) that fail to elongate, and reduced Pax6 ‐positive cells at the branching point of the principal mammillary and mtt. These data suggest that Pitx2 mediates cell‐autonomous and nonautonomous guidance cues necessary for mammillary collaterals destined to project to the anterior thalamus. genesis 50:67–73, 2012. © 2011 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90263/1/20793_ftp.pd

Extensive Spectroscopy and Photometry of the Type IIP Supernova 2013ej

We present extensive optical ($UBVRI$, $g'r'i'z'$, and open CCD) and near-infrared ($ZYJH$) photometry for the very nearby Type IIP SN ~2013ej extending from +1 to +461 days after shock breakout, estimated to be MJD $56496.9\pm0.3$. Substantial time series ultraviolet and optical spectroscopy obtained from +8 to +135 days are also presented. Considering well-observed SNe IIP from the literature, we derive $UBVRIJHK$ bolometric calibrations from $UBVRI$ and unfiltered measurements that potentially reach 2\% precision with a $B-V$ color-dependent correction. We observe moderately strong Si II $\lambda6355$ as early as +8 days. The photospheric velocity ($v_{\rm ph}$) is determined by modeling the spectra in the vicinity of Fe II $\lambda5169$ whenever observed, and interpolating at photometric epochs based on a semianalytic method. This gives $v_{\rm ph} = 4500\pm500$ km s$^{-1}$ at +50 days. We also observe spectral homogeneity of ultraviolet spectra at +10--12 days for SNe IIP, while variations are evident a week after explosion. Using the expanding photosphere method, from combined analysis of SN 2013ej and SN 2002ap, we estimate the distance to the host galaxy to be $9.0_{-0.6}^{+0.4}$ Mpc, consistent with distance estimates from other methods. Photometric and spectroscopic analysis during the plateau phase, which we estimated to be $94\pm7$ days long, yields an explosion energy of $0.9\pm0.3\times10^{51}$ ergs, a final pre-explosion progenitor mass of $15.2\pm4.2$~M$_\odot$ and a radius of $250\pm70$~R$_\odot$. We observe a broken exponential profile beyond +120 days, with a break point at +$183\pm16$ days. Measurements beyond this break time yield a $^{56}$Ni mass of $0.013\pm0.001$~M$_\odot$.Comment: 29 pages, 23 figures, 15 tables, Published in The Astrophisical Journa

The continuing story of SN IIb 2013df: new optical and IR observations and analysis

This work has been supported by the Hungarian Scientific Research Fund (OTKA) Grants NN107637, K104607, K83790, and K113117. TS is supported by the OTKA Postdoctoral Fellowship PD112325. JCW’s Supernova group at the UT Austin is supported by NSF Grant AST 11-09881 grant. JMS is supported by an NSF Astronomy and Astrophysics Postdoctoral Fellowship under award AST-1302771. KS and AP are supported by the ‘Lend¨ulet-2009’ Young Researchers Program and the LP2012-31 grant of the Hungarian Academy of Sciences, respectively; KS is also supported by the ESA PECS Contract no. 4000110889/14/NL/NDe.SN 2013df is a nearby Type IIb supernova that seems to be the spectroscopic twin of the well-known SN 1993J. Previous studies revealed many, but not all interesting properties of this event. Our goal was to add new understanding of both the early- and late-time phases of SN 2013df. Our spectral analysis is based on six optical spectra obtained with the 9.2 m Hobby-Eberly Telescope during the first month after explosion, complemented by a near-infrared spectrum. We applied the SYNAPPS spectral synthesis code to constrain the chemical composition and physical properties of the ejecta. A principal result is the identification of 'high-velocity' He i lines in the early spectra of SN 2013df, manifest as the blue component of the double-troughed profile at ~5650 Å. This finding, together with the lack of clear separation of H and He lines in velocity space, indicates that both H and He features form at the outer envelope during the early phases. We also obtained ground-based BVRI and g'r'i'z' photometric data up to +45 d and unfiltered measurements with the ROTSE-IIIb telescope up to +168 d. From the modelling of the early-time quasi-bolometric light curve, we find Mej ~ 3.2-4.6 M⊙ and Ekin ~ 2.6-2.8 × 1051 erg for the initial ejecta mass and the initial kinetic energy, respectively, which agree well with the values derived from the separate modelling of the light-curve tail. Late-time mid-infrared excess indicates circumstellar interaction starting ~1 yr after explosion, in accordance with previously published optical, X-ray, and radio data.Publisher PDFPeer reviewe

Absolute Distances to Nearby Type Ia Supernovae via Light Curve Fitting Methods

We present a comparative study of absolute distances to a sample of very nearby, bright Type Ia supernovae (SNe) derived from high cadence, high signal-to-noise, multi-band photometric data. Our sample consists of four SNe: 2012cg, 2012ht, 2013dy and 2014J. We present new homogeneous, high-cadence photometric data in Johnson-Cousins BVRI and Sloan g' r' i' z' bands taken from two sites (Piszkesteto and Baja, Hungary), and the light curves are analyzed with publicly available light curve fitters (MLCS2k2, SNooPy2 and SALT2.4). When comparing the best-fit parameters provided by the different codes, it is found that the distance moduli of moderately reddened SNe Ia agree within less than or similar to 0.2 mag, and the agreement is even better (less than or similar to 0.1 mag) for the highest signal-to-noise BVRI data. For the highly reddened SN 2014J the dispersion of the inferred distance moduli is slightly higher. These SN-based distances are in good agreement with the Cepheid distances to their host galaxies. We conclude that the current state-of-the-art light curve fitters for Type Ia SNe can provide consistent absolute distance moduli having less than similar to 0.1-0.2 mag uncertainty for nearby SNe. Still, there is room for future improvements to reach the desired similar to 0.05 mag accuracy in the absolute distance modulus

Efficient mouse transgenesis using Gateway-compatible ROSA26 locus targeting vectors and F1 hybrid ES cells

The ability to rapidly and efficiently generate reliable Cre/loxP conditional transgenic mice would greatly complement global high-throughput gene targeting initiatives aimed at identifying gene function in the mouse. We report here the generation of Cre/loxP conditional ROSA26-targeted ES cells within 3–4 weeks by using Gateway® cloning to build the target vectors. The cDNA of the gene of interest can be expressed either directly by the ROSA26 promoter providing a moderate level of expression or by a CAGG promoter placed in the ROSA26 locus providing higher transgene expression. Utilization of F1 hybrid ES cells with exceptional developmental potential allows the production of germ line transmitting, fully or highly ES cell-derived mice by aggregation of cells with diploid embryos. The presented streamlined procedures accelerate the examination of phenotypical consequences of transgene expression. It also provides a unique tool for comparing the biological activity of polymorphic or splice variants of a gene, or products of different genes functioning in the same or parallel pathways in an overlapping manner

Analysis of Y chromosome STR haplotypes in the European part of Russia reveals high diversities but non-significant genetic distances between populations

A total of 17 Y-specific STR loci were studied in 12 districts of the European part of Russia aiming to ascertain the amount of substructure required for the construction of a representative regional database. All groups exhibited high haplotype diversities but low inter-population variance as measured by an analysis of molecular variance. However, when Western Russia is taken as a whole, the genetic distances to the neighbouring populations were significant. Whereas gradual change in the Y chromosome pool exists between Russia and the Slavic-speaking populations to the West, remarkable discontinuities were observed with neighbouring populations in the East, North and South

Reconstruction of the gravitational wave signal h(t)h(t) during the Virgo science runs and independent validation with a photon calibrator

The Virgo detector is a kilometer-scale interferometer for gravitational wave detection located near Pisa (Italy). About 13 months of data were accumulated during four science runs (VSR1, VSR2, VSR3 and VSR4) between May 2007 and September 2011, with increasing sensitivity. In this paper, the method used to reconstruct, in the range 10 Hz-10 kHz, the gravitational wave strain time series $h(t)$ from the detector signals is described. The standard consistency checks of the reconstruction are discussed and used to estimate the systematic uncertainties of the $h(t)$ signal as a function of frequency. Finally, an independent setup, the photon calibrator, is described and used to validate the reconstructed $h(t)$ signal and the associated uncertainties. The uncertainties of the $h(t)$ time series are estimated to be 8% in amplitude. The uncertainty of the phase of $h(t)$ is 50 mrad at 10 Hz with a frequency dependence following a delay of 8 $\mu$s at high frequency. A bias lower than $4\,\mathrm{\mu s}$ and depending on the sky direction of the GW is also present.Comment: 35 pages, 16 figures. Accepted by CQ

Continent-wide decoupling of Y-chromosomal genetic variation from language and geography in native South Americans

Numerous studies of human populations in Europe and Asia have revealed a concordance between their extant genetic structure and the prevailing regional pattern of geography and language. For native South Americans, however, such evidence has been lacking so far. Therefore, we examined the relationship between Y-chromosomal genotype on the one hand, and male geographic origin and linguistic affiliation on the other, in the largest study of South American natives to date in terms of sampled individuals and populations. A total of 1,011 individuals, representing 50 tribal populations from 81 settlements, were genotyped for up to 17 short tandem repeat (STR) markers and 16 single nucleotide polymorphisms (Y-SNPs), the latter resolving phylogenetic lineages Q and C. Virtually no structure became apparent for the extant Y-chromosomal genetic variation of South American males that could sensibly be related to their inter-tribal geographic and linguistic relationships. This continent-wide decoupling is consistent with a rapid peopling of the continent followed by long periods of isolation in small groups. Furthermore, for the first time, we identified a distinct geographical cluster of Y-SNP lineages C-M217 (C3*) in South America. Such haplotypes are virtually absent from North and Central America, but occur at high frequency in Asia. Together with the locally confined Y-STR autocorrelation observed in our study as a whole, the available data therefore suggest a late introduction of C3* into South America no more than 6,000 years ago, perhaps via coastal or trans-Pacific routes. Extensive simulations revealed that the observed lack of haplogroup C3* among extant North and Central American natives is only compatible with low levels of migration between the ancestor populations of C3* carriers and non-carriers. In summary, our data highlight the fact that a pronounced correlation between genetic and geographic/cultural structure can only be expected under very specific conditions, most of which are likely not to have been met by the ancestors of native South Americans