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Unrecognized mutations in DPYD* 2 A wild-type rectal cancer patients receiving postoperative 5-FU-based chemotherapy - do they have a clinical impact?
No full textAbstract Purpose The impact of the unrecognized mutational dihydropyrimidine-dehydrogenase-gene-( DPYD ) - status on high-grade CTC-AE-grades ≥ 3 (NCI-Common Terminology Criteria for Adverse Events, vs. 3.0) was assessed in patients with upper rectal cancer (inferior tumor margin ≥ 12 cm above the anal verge) treated with upfront surgery and 5-Fluorouracil (5-FU) based adjuvant chemotherapy (CTx). Methods 75 participants of the GAST-05-phase-IIb-trial (ISRCTN35198481) were tested in this single center analysis for DPYD *2A-wildtype (WT) at staging. After surgery, 43 patients (stages II and III, according to the current 8th TNM/UICC-classification, 2017) received FOLFOX-CTx and entered follow-up (median: 101 months). According to recent recommendations of the European Medicines Agency (EMA) and national guidelines, post-hoc genotyping for DPYD *2A (c.1905 + 1G > A; IVS14 + 1G > A; rs3918290), DPYD *13 (c.1679T > G; rs55886062), polymorphism c.2846 A > T (rs67376798) and Haplotype B3 (HapB3) (c.1236G > A; c.1129–5923 C > G) was performed using cryopreserved blood samples and standardized PCR-techniques. Results Five patients were found to have a heterozygous (het_) DPYD -HapB3-status. Across all patients, the adherence to CTx-cycles 1 to 4 was 100%, 97.7%, 95.3%, and 93.0%, respectively. Grade ≥ 3 CTC-AEs were observed in 0.9% of both het_HapB3- and WT-patients. The mean administered dose of 5-FU was 68.8% of the target in DPYD -HapB3 carriers, compared to 92.6% in 38 WT patients. Logistic regression analysis revealed that 5-FU dose reductions were significantly associated with DPYD -HapB3 carrier status (odds ratio [OR] 12.55, p = 0.044) and male sex (OR 0.23, p = 0.049). During follow-up het_HapB3-patients had a recurrence rate of 60.0%, compared to 13,6% for WT-patients. The disease-free survival (DFS) for het_HapB3-patients was significantly reduced vs. WT ( p = 0.010). Multivariable analysis showed that het_HapB3-patients had an increased risk for reduced DFS (HR 3.774; p = 0.057). Interestingly, 5-FU dose reductions per se were not significantly associated with limited DFS in the total population. Conclusion DPYD genotyping revealed a het_HapB3 variant in 11.6% of DPYD *2A-WT patients treated with FOLFOX. While not linked to increased toxicity, HapB3 status was associated with reduced DFS, suggesting an impact on treatment efficacy. These results support DPYD genotyping and highlight the need for adequate 5-FU plasma level assessment followed by subtile dose escalation (therapeutic drug monitoring) to personalize 5-FU dosing more precisely, safely and most effective
Infant Carrying in Wild Black‐Fronted Saddleback Tamarin Groups With Single and Two Breeding Females
No full textABSTRACT In the cooperatively breeding tamarins and marmosets, helpers aid in the transport of heavy twins (15%–20% of maternal body mass at birth). In the few tamarin species studied so far in the wild, the principal infant carriers are breeding adult males, nonbreeding adults and subadults with considerable variation among individuals in their contributions. While tamarin groups usually include only a single breeding female, but groups occasionally include two breeding females. It is not known if and how the number of breeding females affects individual contributions to infant carrying. We studied the mating system of five groups of black‐fronted saddleback tamarins, Leontocebus nigrifrons , in northeastern Peru. Two of the five groups included two breeding females, providing the opportunity to compare patterns of infant carrying in groups with a single breeding female and with two breeding females. Overall, adult males and mothers were the principal carriers. In one group with two breeding females, all adult and subadult group members contributed substantially to infant carrying. In the other group the mother received little help and carried her offspring for > 80% of time. In the former group, both females had copulated with both adult males, while in the latter group the female not receiving help had not copulated with the single adult male of the group. These contrasting patterns of infant carrying highlight the high variability within the cooperative breeding system of tamarins.Spanish version of abstract Dentro del sistema cooperativa de crianza en tamarinos y marmosets, ayudantes contribuen al cargar de los mellizos pesados (al nacer poseen 15%–20% de la masa corporal de la madre). En las pocas especies de tamarinos estudiadios en medio natural, los cargadores principales aparte de los machos adultos son otros adultos y subadultos, con considerable variación en las contribuciones individuales. Por regla general, grupos de tamarinos incluyen una sola hembra reproductora, pero reproducción por una segunda hembra occure de vez en cuando. No se sabe si y como eso afecta a las contribuciones indivuales al cargar las crías. En un estudio sobre el sistema de apareamiento del tamarino de frente negro, Leontocebus nigrifrons , en el nororiente peruano, dos de los cinco grupos de estudio incluían dos hembras reproductoras. Eso presentaba la oportunidad de comparar patrones de cargar las crías entre grupos con una sola hembra reproductora y con dos hembras reproductoras. En general, los machos adultos y las hembras reproductoras (madres) eran los cargadores principales. Mientras que en un grupo con dos hembras reproductoras todos los adultos y subadultos contribuían considerablemente al cargar las crías, en el otro grupo la madre recibía poco ayuda y cargaba sus crías por > 80% del tiempo. En el primer grupo, ambas hembras reproductoras habían copulado con los dos machos adultos, en el segundo grupo la hembra que no recibía ayuda no había copulado con el único macho del grupo. Estos patrones opuestos enfatizan la alta variabilidad del sistema cooperativo de crianza de los tamarinos.Summary In wild cooperatively breeding tamarins, adult males and mothers are the principal carriers of infants, both in groups with a single and with two breeding females. Patterns of infant carrying vary between groups with two breeding females, perhaps in relation to the probability of paternity, genetic relationship and energetic costs. The study adds further evidence to the complexity of the callitrichid cooperative breeding system.ABSTRACT In the cooperatively breeding tamarins and marmosets, helpers aid in the transport of heavy twins (15%–20% of maternal body mass at birth). In the few tamarin species studied so far in the wild, the principal infant carriers are breeding adult males, nonbreeding adults and subadults with considerable variation among individuals in their contributions. While tamarin groups usually include only a single breeding female, but groups occasionally include two breeding females. It is not known if and how the number of breeding females affects individual contributions to infant carrying. We studied the mating system of five groups of black‐fronted saddleback tamarins, Leontocebus nigrifrons , in northeastern Peru. Two of the five groups included two breeding females, providing the opportunity to compare patterns of infant carrying in groups with a single breeding female and with two breeding females. Overall, adult males and mothers were the principal carriers. In one group with two breeding females, all adult and subadult group members contributed substantially to infant carrying. In the other group the mother received little help and carried her offspring for > 80% of time. In the former group, both females had copulated with both adult males, while in the latter group the female not receiving help had not copulated with the single adult male of the group. These contrasting patterns of infant carrying highlight the high variability within the cooperative breeding system of tamarins.Spanish version of abstract Dentro del sistema cooperativa de crianza en tamarinos y marmosets, ayudantes contribuen al cargar de los mellizos pesados (al nacer poseen 15%–20% de la masa corporal de la madre). En las pocas especies de tamarinos estudiadios en medio natural, los cargadores principales aparte de los machos adultos son otros adultos y subadultos, con considerable variación en las contribuciones individuales. Por regla general, grupos de tamarinos incluyen una sola hembra reproductora, pero reproducción por una segunda hembra occure de vez en cuando. No se sabe si y como eso afecta a las contribuciones indivuales al cargar las crías. En un estudio sobre el sistema de apareamiento del tamarino de frente negro, Leontocebus nigrifrons , en el nororiente peruano, dos de los cinco grupos de estudio incluían dos hembras reproductoras. Eso presentaba la oportunidad de comparar patrones de cargar las crías entre grupos con una sola hembra reproductora y con dos hembras reproductoras. En general, los machos adultos y las hembras reproductoras (madres) eran los cargadores principales. Mientras que en un grupo con dos hembras reproductoras todos los adultos y subadultos contribuían considerablemente al cargar las crías, en el otro grupo la madre recibía poco ayuda y cargaba sus crías por > 80% del tiempo. En el primer grupo, ambas hembras reproductoras habían copulado con los dos machos adultos, en el segundo grupo la hembra que no recibía ayuda no había copulado con el único macho del grupo. Estos patrones opuestos enfatizan la alta variabilidad del sistema cooperativo de crianza de los tamarinos.Summary In wild cooperatively breeding tamarins, adult males and mothers are the principal carriers of infants, both in groups with a single and with two breeding females. Patterns of infant carrying vary between groups with two breeding females, perhaps in relation to the probability of paternity, genetic relationship and energetic costs. The study adds further evidence to the complexity of the callitrichid cooperative breeding system.ABSTRACT In the cooperatively breeding tamarins and marmosets, helpers aid in the transport of heavy twins (15%–20% of maternal body mass at birth). In the few tamarin species studied so far in the wild, the principal infant carriers are breeding adult males, nonbreeding adults and subadults with considerable variation among individuals in their contributions. While tamarin groups usually include only a single breeding female, but groups occasionally include two breeding females. It is not known if and how the number of breeding females affects individual contributions to infant carrying. We studied the mating system of five groups of black‐fronted saddleback tamarins, Leontocebus nigrifrons , in northeastern Peru. Two of the five groups included two breeding females, providing the opportunity to compare patterns of infant carrying in groups with a single breeding female and with two breeding females. Overall, adult males and mothers were the principal carriers. In one group with two breeding females, all adult and subadult group members contributed substantially to infant carrying. In the other group the mother received little help and carried her offspring for > 80% of time. In the former group, both females had copulated with both adult males, while in the latter group the female not receiving help had not copulated with the single adult male of the group. These contrasting patterns of infant carrying highlight the high variability within the cooperative breeding system of tamarins.Spanish version of abstract Dentro del sistema cooperativa de crianza en tamarinos y marmosets, ayudantes contribuen al cargar de los mellizos pesados (al nacer poseen 15%–20% de la masa corporal de la madre). En las pocas especies de tamarinos estudiadios en medio natural, los cargadores principales aparte de los machos adultos son otros adultos y subadultos, con considerable variación en las contribuciones individuales. Por regla general, grupos de tamarinos incluyen una sola hembra reproductora, pero reproducción por una segunda hembra occure de vez en cuando. No se sabe si y como eso afecta a las contribuciones indivuales al cargar las crías. En un estudio sobre el sistema de apareamiento del tamarino de frente negro, Leontocebus nigrifrons , en el nororiente peruano, dos de los cinco grupos de estudio incluían dos hembras reproductoras. Eso presentaba la oportunidad de comparar patrones de cargar las crías entre grupos con una sola hembra reproductora y con dos hembras reproductoras. En general, los machos adultos y las hembras reproductoras (madres) eran los cargadores principales. Mientras que en un grupo con dos hembras reproductoras todos los adultos y subadultos contribuían considerablemente al cargar las crías, en el otro grupo la madre recibía poco ayuda y cargaba sus crías por > 80% del tiempo. En el primer grupo, ambas hembras reproductoras habían copulado con los dos machos adultos, en el segundo grupo la hembra que no recibía ayuda no había copulado con el único macho del grupo. Estos patrones opuestos enfatizan la alta variabilidad del sistema cooperativo de crianza de los tamarinos.Summary In wild cooperatively breeding tamarins, adult males and mothers are the principal carriers of infants, both in groups with a single and with two breeding females. Patterns of infant carrying vary between groups with two breeding females, perhaps in relation to the probability of paternity, genetic relationship and energetic costs. The study adds further evidence to the complexity of the callitrichid cooperative breeding system
Correction: Neural autoantibodies in psychiatric disorders are associated with antibodies against viral pathogens: a retrospective study of 619 patients
No full textComparative outcomes of liver transplantation and liver resection in hepatitis B and C patients with hepatocellular carcinoma
No full textMechanisms of left–right symmetry breaking across scales
No full texthttp://dx.doi.org/10.13039/501100001459 Government of Singapore Ministry of Educationhttp://dx.doi.org/10.13039/501100001381 National Research Foundationhttp://dx.doi.org/10.13039/100019147 Universitätsmedizin Göttingenhttp://dx.doi.org/10.13039/501100001352 National University of Singaporehttp://dx.doi.org/10.13039/501100007672 Mechanobiology Institute, Singapor
Sounds good, doesn't work - an experimental study on the dynamic development of trust in digital systems under inconsistent information about developer reputation and system errors
No full textFiscal pro-cyclicality revisited: Global, regional, and country-level evidence with a spotlight on MENA
No full textHermeneutisk dialog, eller mangel på samme – en kort bemærkning
No full textHermeneutic Dialogue, or Lack Thereof – A Short Remark
In his short answer to my rejoinder, Sebastian Olden-Jørgensen seeks to close down the discussion without first taking part in it. He refuses to explain his claim that Holberg was an atypical member of the republic of letters and he seeks, too, to avoid the discussion about the concepts he uses to interpret Holberg. This, I argue, is a problematic disposition, not least because his definition of the republic of letters and Holberg’s role within it is rather peculiar. Instead, Olden-Jørgensen unfolds what he sees as his hermeneutic and humanist approach to the past. Yet, as I further argue, Olden-Jørgensen’s understanding of hermeneutics does not entail dialogue. Scholarly critique is mistaken for ad hominem arguments. For Olden-Jørgensen, critical engagement is a one-way traffic in which one part is only allowed to repeat what the other one says. This is not scholarly dialogue, but a lack thereof
Das Herzstück des EDCH - die Registry und das Forum
No full textDieser Blogpost beschreibt, wie die Diamond Open Access Community den European Diamond Capacity Hub für Vernetzung und Sichtbarkeit nutzen kann. Im Post wird genauer auf die Funktionalitäten der Registry und des Forums eingegangen
Development of a Rapid Isothermal Assay for Detection of Adenovirus Types Important in Respiratory Infections
No full textNucleic acid amplification tests (NAATs) for human adenoviruses (HAdVs) causing respiratory infections usually target the hexon gene. However, new HAdV types with substantial variations in the hexon gene may not be detected. Thus, we focus on NAATs based on a conserved region in the penton gene to detect all HAdV types causing respiratory infections