Prevalence and management of iron overload in pyruvate kinase deficiency: report from the Pyruvate Kinase Deficiency Natural History Study

Pyruvate kinase (PK) deficiency is the most common red cell glycolytic enzyme defect causing hereditary non-spherocytic hemolytic anemia. Current treatments are mainly supportive and include red cell transfusions and splenectomy.11 Regular red cell transfusions are known to result in iron overload; however, the prevalence and spectrum of transfusion-independent iron overload in the overall PK deficient population has not been well defined. This analysis describes the prevalence and clinical characteristics of iron overload in patients enrolled in the PK Deficiency Natural History Study (NHS) with a focus on those patients who are not regularly transfused.

CS 30322-023: an ultra metal-poor TP-AGB star?

With [Fe/H] = -3.5, CS 30322-023 is the most metal-poor star to exhibit a clear s-process signature and the most metal-poor ``lead star'' known. CS 30322-023 is also remarkable in having the lowest surface gravity (log g <= -0.3) among the metal-poor stars studied to date. The available evidence indicates that this star is presently a thermally-pulsing asymptotic giant branch (TP-AGB) star, with no strong indication of binarity thus far (although a signal of period 192 d is clearly present in the radial-velocity data, this is likely due to pulsation of the stellar envelope). We show that low-mass TP-AGB stars are not expected to be exceedingly rare in a magnitude-limited sample such as the HK survey, because their high luminosities make it possible to sample them over a very large volume. The strong N overabundance and the low 12C/13C ratio (4) in this star is typical of the operation of the CN cycle. Coupled with a Na overabundance and the absence of a strong C overabundance, this pattern seems to imply that hot-bottom burning operated in this star, which should then have a mass of at least 2 Msun. However, the luminosity associated with this mass would put the star at a distance of about 50 kpc, in the outskirts of the galactic halo. We explore alternative scenarios in which the observed abundance pattern results from some mixing mechanism yet to be identified occurring in a single low-metallicity 0.8 Msun AGB star, or from pollution by matter from an intermediate-mass AGB companion which has undergone hot-bottom burning. We stress, however, that our abundances may be subject to uncertainties due to NLTE or 3D granulation effects which were not taken into consideration.Comment: 17 pages, Astronomy & Astrophysics, in press; also available at http://www.astro.ulb.ac.be/Html/ps.html#PR

Commercial DNA tests and police investigations: a broad bioethical perspective

Over 30 million people worldwide have taken a commercial at-home DNA test, because they were interested in their genetic ancestry, disease predisposition or inherited traits. Yet, these consumer DNA data are also increasingly used for a very different purpose: to identify suspects in criminal investigations. By matching a suspect’s DNA with DNA from a suspect’s distant relatives who have taken a commercial at-home DNA test, law enforcement can zero in on a perpetrator. Such forensic use of consumer DNA data has been performed in over 200 criminal investigations. However, this practice of so-called investigative genetic genealogy (IGG) raises ethical concerns. In this paper, we aim to broaden the bioethical analysis on IGG by showing the limitations of an individual-based model. We discuss two concerns central in the debate: privacy and informed consent. However, we argue that IGG raises pressing ethical concerns that extend beyond these individual-focused issues. The very nature of the genetic information entails that relatives may also be affected by the individual customer’s choices. In this respect, we explore to what extent the ethical approach in the biomedical genetic context on consent and consequences for relatives can be helpful for the debate on IGG. We argue that an individual-based model has significant limitations in an IGG context. The ethical debate is further complicated by the international, transgenerational and commercial nature of IGG. We conclude that IGG should not only be approached as an individual but also—and perhaps primarily—as a collective issue.There are no data in this work

Detection of the hydroperoxyl radical HO2 toward \rho Oph A: Additional constraints on the water chemical network

Context: Hydrogen peroxide (HOOH) was recently detected toward \rho Oph A. Subsequent astrochemical modeling that included reactions in the gas phase and on the surface of dust grains was able to explain the observed abundance, and highlighted the importance of grain chemistry in the formation of HOOH as an intermediate product in water formation. This study also predicted that the hydroperoxyl radical HO2, the precursor of HOOH, should be detectable. Aims: We aim at detecting the hydroperoxyl radical HO2 in \rho Oph A. Methods: We used the IRAM 30m and the APEX telescopes to target the brightest HO2 lines at about 130 and 260 GHz. Results: We detect five lines of HO2 (comprising seven individual molecular transitions). The fractional abundance of HO2 is found to be about 1e-10, a value similar to the abundance of HOOH. This observational result is consistent with the prediction of the above mentioned astrochemical model, and thereby validates our current understanding of the water formation on dust grains. Conclusions: This detection, anticipated by a sophisticated gas-grain chemical model, demonstrates that models of grain chemistry have improved tremendously and that grain surface reactions now form a crucial part of the overall astrochemical network.Comment: 5 pages, 4 figures, accepted for publication as a Letter to the Editor in Astronomy and Astrophysic

Automated array-CGH optimized for archival formalin-fixed, paraffin-embedded tumor material

BACKGROUND: Array Comparative Genomic Hybridization (aCGH) is a rapidly evolving technology that still lacks complete standardization. Yet, it is of great importance to obtain robust and reproducible data to enable meaningful multiple hybridization comparisons. Special difficulties arise when aCGH is performed on archival formalin-fixed, paraffin-embedded (FFPE) tissue due to its variable DNA quality. Recently, we have developed an effective DNA quality test that predicts suitability of archival samples for BAC aCGH. METHODS: In this report, we first used DNA from a cancer cell-line (SKBR3) to optimize the aCGH protocol for automated hybridization, and subsequently optimized and validated the procedure for FFPE breast cancer samples. We aimed for highest throughput, accuracy, and reproducibility applicable to FFPE samples, which can also be important in future diagnostic use. RESULTS: Our protocol of automated array-CGH on archival FFPE ULS-labeled DNA showed very similar results compared with published data and our previous manual hybridization method. CONCLUSION: This report combines automated aCGH on unamplified archival FFPE DNA using non-enzymatic ULS labeling, and describes an optimized protocol for this combination resulting in improved quality and reproducibility