46 research outputs found

    Malignant extracranial germ cell tumors in the Netherlands between 1990 and 2018: Stable incidence and improved survival

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    Background: Population-based studies assessing long-term patterns of incidence and disease characteristics of germ cell tumors (GCTs) in children are scarce. We investigated incidence and survival trends of malignant extracranial GCTs in children using population-based nationwide data from the Netherlands. Methods: All malignant extracranial GCTs diagnosed in patients aged 0–18 years between 1990 and 2018 were selected from the Netherlands Cancer Registry. Incidence rates were calculated as the average annual number of cases per 1 million person-years. Five-year overall survival (OS) was calculated. Results: A total of 815 cases were identified. Gonadal GCTs (n=665, testis n=485, ovarian n=180) were more common than extragonadal GCTs (n=149). Stage distribution for testicular and extragonadal GCTs shifted between 1990 and 2004 and 2005–2018 towards more localized disease. The overall incidence remained stable over time, but a significant increase was noted for extragonadal GCTs in the 0–9 years age group. Survival of extragonadal GCTs (5-year OS 84.1%, 95% CI 77.1–89.1), in particular mediastinal GCTs (5-year OS 66.7%, 95% CI 45.7–81.1), was lower than that of gonadal GCTs (5-year OS testis 95.0%, 95% CI 92.7–96.7;ovary 97.8%, 95% CI 94.2–99.2). The 5-year OS of our entire cohort was 93.6% (95% CI 91.7–95.1). Five-year OS significantly increased from 89.5% (95% CI 86.1–92.2) in 1990–2004–97.4% (95% CI 95.3–98.5) in 2005–2018. Conclusions: Although the incidence of all malignant pediatric extracranial GCTs remained stable during 1990–2018, an increase was observed for extragonadal GCTs in younger children (0–9 years). There was a shift towards more localized disease for testicular and extragonadal GCTs. Five-year OS increased over time exceeding 90% (91.4%, 95% CI 82.7–95.8) in the most recent diagnostic period. Mediastinal GCTs had the lowest OS, supporting the need for future research

    Current and Future Prospects of Nitro-compounds as Drugs for Trypanosomiasis and Leishmaniasis

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    Investigations of the Mars Upper Atmosphere with ExoMars Trace Gas Orbiter

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    The Martian mesosphere and thermosphere, the region above about 60 km, is not the primary target of the ExoMars 2016 mission but its Trace Gas Orbiter (TGO) can explore it and address many interesting issues, either in-situ during the aerobraking period or remotely during the regular mission. In the aerobraking phase TGO peeks into thermospheric densities and temperatures, in a broad range of latitudes and during a long continuous period. TGO carries two instruments designed for the detection of trace species, NOMAD and ACS, which will use the solar occultation technique. Their regular sounding at the terminator up to very high altitudes in many different molecular bands will represent the first time that an extensive and precise dataset of densities and hopefully temperatures are obtained at those altitudes and local times on Mars. But there are additional capabilities in TGO for studying the upper atmosphere of Mars, and we review them briefly. Our simulations suggest that airglow emissions from the UV to the IR might be observed outside the terminator. If eventually confirmed from orbit, they would supply new information about atmospheric dynamics and variability. However, their optimal exploitation requires a special spacecraft pointing, currently not considered in the regular operations but feasible in our opinion. We discuss the synergy between the TGO instruments, specially the wide spectral range achieved by combining them. We also encourage coordinated operations with other Mars-observing missions capable of supplying simultaneous measurements of its upper atmosphere

    Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

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    Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk
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