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- Mavaddat, N, et al.
(författare)
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Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers
- 2020
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Ingår i: Breast cancer research : BCR. - : Springer Science and Business Media LLC. - 1465-542X. ; 22:1, s. 8-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer risk forBRCA1andBRCA2mutation carriers is uncertain. Retrospective analyses have suggested a protective effect but may be substantially biased. Prospective studies have had limited power, particularly forBRCA2mutation carriers. Further, previous studies have not considered the effect of RRSO in the context of natural menopause.MethodsA multi-centre prospective cohort of 2272BRCA1and 1605BRCA2mutation carriers was followed for a mean of 5.4 and 4.9 years, respectively; 426 women developed incident breast cancer. RRSO was modelled as a time-dependent covariate in Cox regression, and its effect assessed in premenopausal and postmenopausal women.ResultsThere was no association between RRSO and breast cancer forBRCA1(HR = 1.23; 95% CI 0.94–1.61) orBRCA2(HR = 0.88; 95% CI 0.62–1.24) mutation carriers. ForBRCA2mutation carriers, HRs were 0.68 (95% CI 0.40–1.15) and 1.07 (95% CI 0.69–1.64) for RRSO carried out before or after age 45 years, respectively. The HR forBRCA2mutation carriers decreased with increasing time since RRSO (HR = 0.51; 95% CI 0.26–0.99 for 5 years or longer after RRSO). Estimates for premenopausal women were similar.ConclusionWe found no evidence that RRSO reduces breast cancer risk forBRCA1mutation carriers. A potentially beneficial effect forBRCA2mutation carriers was observed, particularly after 5 years following RRSO. These results may inform counselling and management of carriers with respect to RRSO.
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- Kuiper, Jan J., et al.
(författare)
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Exploring desirable nature futures for Nationaal Park Hollandse Duinen
- 2022
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Ingår i: Ecosystems and People. - : Informa UK Limited. - 2639-5908 .- 2639-5916. ; 18:1, s. 329-347
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Tidskriftsartikel (refereegranskat)abstract
- Achieving global sustainability goals requires most people and societies to fundamentally revisit their relationship with nature. New approaches are called for to guide change processes towards sustainable futures that embrace the plurality of people’s desired relationships with nature. This paper presents a novel approach to exploring desirable futures for nature and people that was developed through an application in Nationaal Park Hollandse Duinen in the Netherlands. This new national park is developed bottom-up by a diverse group of actors reshaping their interactions with each other and with nature. Our approach, co-designed with key stakeholders of the national park, engages with a new pluralistic framework for human-nature relationships presented by the IPBES task force on scenarios and models to catalyze the development of nature-centered scenarios. We integrated this Nature Futures Framework with the Three Horizons Framework in a participatory workshop process designed to bring people’s diverse relationships with nature to the fore, and jointly envision desirable futures and the pathways to get there. We present a methodology to analyze and compare the visions and assess their potential contribution to the SDGs. We summarize the results of the application in Nationaal Park Hollandse Duinen and reflect on lessons learned. The approach successfully engaged participants in joint exploration of desirable futures for the national park based on their plural perspectives on human-nature relationships. We see much potential for its applications to support change processes in various social-ecological contexts toward more sustainable futures for nature and people.
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- Aartse, A, et al.
(författare)
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Primary antibody response after influenza virus infection is first dominated by low-mutated HA-stem antibodies followed by higher-mutated HA-head antibodies
- 2022
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 13, s. 1026951-
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have shown that the first encounter with influenza virus shapes the immune response to future infections or vaccinations. However, a detailed analysis of the primary antibody response is lacking as this is difficult to study in humans. It is therefore not known what the frequency and dynamics of the strain-specific hemagglutinin (HA) head- and stem-directed antibody responses are directly after primary influenza virus infection. Here, sera of twelve H1N1pdm2009 influenza virus-infected cynomolgus macaques were evaluated for HA-head and HA-stem domain antibody responses. We observed an early induction of HA-stem antibody responses, which was already decreased by day 56. In contrast, responses against the HA-head domain were low early after infection and increased at later timepoint. The HA-specific B cell repertoires in each animal showed diverse VH-gene usage with preferred VH-gene and JH-gene family usage for HA-head or HA-stem B cells but a highly diverse allelic variation within the VH-usage. HA-head B cells had shorter CDRH3s and higher VH-gene somatic hyper mutation levels relative to HA-stem B cells. In conclusion, our data suggest that HA-stem antibodies are the first to react to the infection while HA-head antibodies show a delayed response, but a greater propensity to enter the germinal center and undergo affinity maturation.
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- Lammers, Rianne J. M., et al.
(författare)
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"What should be next in lifelong posterior hypospadias: Conclusions from the 2023 ERN eUROGEN and EJP-RD networking meeting"
- 2024
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Ingår i: NEUROUROLOGY AND URODYNAMICS. - 0733-2467 .- 1520-6777.
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Forskningsöversikt (refereegranskat)abstract
- BackgroundA congenital disease is for life. Posterior hypospadias, the severe form of hypospadias with a penoscrotal, scrotal, or perineal meatus, is a challenging condition with a major impact on lifelong quality of life.AimOur network meeting is aimed to identify what is currently missing in the lifelong treatment of posterior hypospadias, to improve care, quality of life, and awareness for these patients.MethodsThe network meeting "Lifelong Posterior Hypospadias" in Utrecht, The Netherlands was granted by the European Joint Programme on Rare Diseases-Networking Support Scheme. There was a combination of interactive sessions (hackathons) and lectures. This paper can be regarded as the last phase of the hackathon.ResultsSurgery for hypospadias remains challenging and complications may occur until adulthood. Posterior hypospadias affects sexual function, fertility, and hormonal status. Transitional care from childhood into adulthood is currently insufficiently established. Patients should be more involved in defining desired treatment approach and outcome measures. For optimal outcome evaluation standardization of data collection and registration at European level is necessary. Tissue engineering may provide a solution to the shortage of healthy tissue in posterior hypospadias. For optimal results, cooperation between basic researchers from different centers, as well as involving clinicians and patients is necessary.ConclusionsTo improve outcomes for patients with posterior hypospadias, patient voices should be included and lifelong care by dedicated healthcare professionals guaranteed. Other requirements are joining forces at European level in uniform registration of outcome data and cooperation in basic research.
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