The complexities in genotyping of congenital adrenal hyperplasia: 21-hydroxylase deficiency

The deficiency of 21-hydroxylase due to CYP21A2 pathogenic variants is a rather frequent disease with serious consequences, going from a real mortality risk to infertility and to milder symptoms, nevertheless important for affecting the patients’ self-esteem. In the most severe cases life-threatening adrenal salt wasting crises may occur. Significant morbidity including the possibility of mistaken gender determination, precocious puberty, infertility and growth arrest with consequent short stature may also affect these patients. In the less severe cases milder symptoms like hirsutism will likely affect the image of the self with strong psychological consequences. Its diagnosis is confirmed by 17OH-progesterone dosages exceeding the cut-off value of 10/15 ng/ml but genotyping is progressively assuming an essential role in the study of these patients particularly in confirming difficult cases, determining some aspects of the prognosis and allowing a correct genetic counseling. Genotyping is a difficult process due to the occurrence of both a gene and a highly homologous pseudo gene. However, new tools are opening new possibilities to this analysis and improving the chances of a correct diagnosis and better understanding of the underlying mechanisms of the disease. Beyond the 10 classic pathogenic variants usually searched for in most laboratories, a correct analysis of 21OH-deficiency cases implies completely sequencing of the entire gene and the determination of gene duplications. These are now recognized to occur frequently and can be responsible for some false positive cases. And finally, because gene conversions can include several pathogenic variants one cannot be certain of identifying that both alleles are affected without studying parental DNA samples. A complete genotype characterization should be considered essential in the preparation for pregnancy, even in the case of parents with milder forms of the disease, or even just carriers, since it has been reported that giving birth to progeny with the severe classic forms occurs with a much higher frequency than expected.The work was supported by the Foundation for Science and Technology (FCT) (PTDC/MEC-ONC/31384/2017). SG was funded through FCT grant SFRH/BPD/1117441/2015

Multi-material NiTi-PEEK hybrid cellular structures by selective laser melting and hot pressing: tribological characterization

In this study, a multi-material NiTi-PEEK cellular structured solution was designed, produced and characterized targeting orthopedic applications. For that purpose, Selective Laser Melting (SLM) technique was used to produce NiTi cellular structures with different open-cell sizes and wall thicknesses. Hot Pressing (HP) technique was used to introduce PEEK in the open-cells of NiTi structures to obtain multi-material components. Morphological characterization showed that the selected SLM processing parameters were suited to achieve high-quality parts without significant defects. Tribological characterization proved an enhanced wear resistance to the multimaterial specimens when compared with the mono-material NiTi structures. These multi-material structures are a promising solution for providing a customized stiffness and superior wear resistance to NiTi structures to be integrated in innovative orthopedic designs.This work was supported by FCT (Fundação para a Ciência e a Tecnologia) through the grant SFRH/BD/140191/2018 and by project NORTE 01–0145_FEDER-000018-HAMaBICo. Additionally, this work is supported by FCT with the reference project UID/EEA/04436/2019

Demonstration of the event identification capabilities of the NEXT-White detector

In experiments searching for neutrinoless double-beta decay, the possibility of identifying the two emitted electrons is a powerful tool in rejecting background events and therefore improving the overall sensitivity of the experiment. In this paper we present the first measurement of the efficiency of a cut based on the different event signatures of double and single electron tracks, using the data of the NEXT-White detector, the first detector of the NEXT experiment operating underground. Using a 228Th calibration source to produce signal-like and background-like events with energies near 1.6 MeV, a signal efficiency of 71.6 ± 1.5 stat± 0.3 sys% for a background acceptance of 20.6 ± 0.4 stat± 0.3 sys% is found, in good agreement with Monte Carlo simulations. An extrapolation to the energy region of the neutrinoless double beta decay by means of Monte Carlo simulations is also carried out, and the results obtained show an improvement in background rejection over those obtained at lower energies. [Figure not available: see fulltext.

Radiogenic backgrounds in the NEXT double beta decay experiment

Natural radioactivity represents one of the main backgrounds in the search for neutrinoless double beta decay. Within the NEXT physics program, the radioactivity- induced backgrounds are measured with the NEXT-White detector. Data from 37.9 days of low-background operations at the Laboratorio Subterráneo de Canfranc with xenon depleted in 136Xe are analyzed to derive a total background rate of (0.84±0.02) mHz above 1000 keV. The comparison of data samples with and without the use of the radon abatement system demonstrates that the contribution of airborne-Rn is negligible. A radiogenic background model is built upon the extensive radiopurity screening campaign conducted by the NEXT collaboration. A spectral fit to this model yields the specific contributions of 60Co, 40K, 214Bi and 208Tl to the total background rate, as well as their location in the detector volumes. The results are used to evaluate the impact of the radiogenic backgrounds in the double beta decay analyses, after the application of topological cuts that reduce the total rate to (0.25±0.01) mHz. Based on the best-fit background model, the NEXT-White median sensitivity to the two-neutrino double beta decay is found to be 3.5σ after 1 year of data taking. The background measurement in a Qββ±100 keV energy window validates the best-fit background model also for the neutrinoless double beta decay search with NEXT-100. Only one event is found, while the model expectation is (0.75±0.12) events. [Figure not available: see fulltext.]

Measurement of radon-induced backgrounds in the NEXT double beta decay experiment

The measurement of the internal $^{222}$Rn activity in the NEXT-White detector during the so-called Run-II period with $^{136}$Xe-depleted xenon is discussed in detail, together with its implications for double beta decay searches in NEXT. The activity is measured through the alpha production rate induced in the fiducial volume by $^{222}$Rn and its alpha-emitting progeny. The specific activity is measured to be $(38.1\pm 2.2~\mathrm{(stat.)}\pm 5.9~\mathrm{(syst.)})$~mBq/m$^3$. Radon-induced electrons have also been characterized from the decay of the $^{214}$Bi daughter ions plating out on the cathode of the time projection chamber. From our studies, we conclude that radon-induced backgrounds are sufficiently low to enable a successful NEXT-100 physics program, as the projected rate contribution should not exceed 0.1~counts/yr in the neutrinoless double beta decay sample.Comment: 28 pages, 10 figures, 6 tables. Version accepted for publication in JHE