| 1. |
- Krege, Susanne, et al.
(författare)
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European consensus conference on diagnosis and treatment of germ cell cancer: A report of the second meeting of the European Germ Cell Cancer Consensus Group (EGCCCG): Part I
- 2008
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 53:3, s. 478-496
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Forskningsöversikt (refereegranskat)abstract
- Objectives: The first consensus report presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in the year 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the Amsterdam Medical Center, Amsterdam, The Netherlands. Methods: Medical oncologists, urological surgeons, radiation oncologists as well as pathologists from several European countries reviewed and discussed the data that had emerged since the 2002 conference, and incorporated the new data into updated and revised guidelines. As for the first meeting, the methodology of evidence-based medicine (EBM) was applied. The results of the discussion were compiled by the writing committee. All participants have agreed to this final update. Results: The first part of the consensus paper describes the clinical presentation of the primary tumor, its treatment, the importance and treatment of testicular intraepithelial neoplasia (TIN), histological classification, staging and prognostic factors, and treatment of stage I seminoma and non-seminoma. Conclusions: Whereas the vast majority of the recommendations made in 2004 remain valid 3 yr later, refinements in the treatment of early- and advanced-stage testicular cancer have emerged from clinical trials. Despite technical improvements, expert clinical skills will continue to be one of the major determinants for the prognosis of patients with germ cell cancer. In addition, the particular needs of testicular cancer survivors have been acknowledged. (C) 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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| 2. |
- Krege, Susanne, et al.
(författare)
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European consensus conference on diagnosis and treatment of germ cell cancer: A report of the second meeting of the European Germ Cell Cancer Consensus Group (EGCCCG): Part II
- 2008
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 53:3, s. 497-513
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Forskningsöversikt (refereegranskat)abstract
- Objectives: The first consensus report that had been presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the Amsterdam Medical Center, The Netherlands. Methods: Medical oncologists, urologic surgeons, radiation oncologists as well as pathologists from several European countries reviewed and discussed the data that had emerged since the 2002 conference and incorporated the new data into updated and revised guidelines. As for the first meeting the methodology of evidence-based medicine (EBM) was applied. The results of the discussion were compiled by the writing committee. All participants have agreed to this final update. Results: The second part of the consensus paper includes the treatment of metastasised disease, residual tumour resection, salvage therapy, follow-up, and late toxicities. Conclusions: Whereas the vast majority of the recommendations made in 2004 remain valid 3 yr later, refinements in the treatment of early-stage as well as of advanced-stage testicular cancer have emerged from clinical trials. Despite technical improvements, expert clinical skills will continue to be one of the major determinants for the prognosis of patients with germ cell cancer. in addition, the particular needs of testicular cancer survivors have been acknowledged. (C) 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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| 3. |
- Romanov, Roman A., et al.
(författare)
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Molecular interrogation of hypothalamic organization reveals distinct dopamine neuronal subtypes
- 2017
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Ingår i: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 20:2, s. 176-188
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Tidskriftsartikel (refereegranskat)abstract
- The hypothalamus contains the highest diversity of neurons in the brain. Many of these neurons can co-release neurotransmitters and neuropeptides in a use-dependent manner. Investigators have hitherto relied on candidate protein-based tools to correlate behavioral, endocrine and gender traits with hypothalamic neuron identity. Here we map neuronal identities in the hypothalamus by single-cell RNA sequencing. We distinguished 62 neuronal subtypes producing glutamatergic, dopaminergic or GABAergic markers for synaptic neurotransmission and harboring the ability to engage in task-dependent neurotransmitter switching. We identified dopamine neurons that uniquely coexpress the Onecut3 and Nmur2 genes, and placed these in the periventricular nucleus with many synaptic afferents arising from neuromedin S+ neurons of the suprachiasmatic nucleus. These neuroendocrine dopamine cells may contribute to the dopaminergic inhibition of prolactin secretion diurnally, as their neuromedin S+ inputs originate from neurons expressing Per2 and Per3 and their tyrosine hydroxylase phosphorylation is regulated in a circadian fashion. Overall, our catalog of neuronal subclasses provides new understanding of. hypothalamic organization and function.
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| 4. |
- Brose, Ulrich, et al.
(författare)
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Spatial aspects of food webs
- 2005
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Ingår i: Dynamic Food Webs. - London, UK : Elsevier. - 9780120884582 - 0120884585 ; , s. 463-469
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Konferensbidrag (refereegranskat)abstract
- Aspects of spatial scale have until recently been largely ignored in empirical and theoretical food web studies (e.g., Cohen & Briand 1984, Martinez 1992, but see Bengtsson et al. 2002, Bengtsson & Berg, this book). Most ecologists tend to conceptualize and represent food webs as static representations of communities, depicting a community assemblage as sampled at a particular point in time, or highly aggregated trophic group composites over broader scales of time and space (Polis et al. 1996). Moreover, most researchers depict potential food webs, which contain all species sampled and all potential trophic links based on literature reviews, several sampling events, or laboratory feeding trials. In reality, however, not all these potential feeding links are realized as not all species co-occur, and not all samples in space or time can contain all species (Schoenly & Cohen 1991), hence, yielding a variance of food web architecture in space (Brose et al. 2004). In recent years, food web ecologists have recognized that food webs are open systems – that are influence by processes in adjacent systems – and spatially heterogeneous (Polis et al. 1996). This influence of adjacent systems can be bottom-up, due to allochthonous inputs of resources (Polis & Strong 1996, Huxel & McCann 1998, Mulder & De Zwart 2003), or top-down due to the regular or irregular presence of top predators (e.g., Post et al. 2000, Scheu 2001). However, without a clear understanding of the size of a system and a definition of its boundaries it is not possible to judge if flows are internal or driven by adjacent systems. Similarly, the importance of allochthony is only assessable when the balance of inputs and outputs are known relative to the scale and throughputs within the system itself. At the largest scale of the food web – the home range of a predator such as wolf, lion, shark or eagle of roughly 50 km2 to 300 km2 –the balance of inputs and outputs caused by wind and movement of water may be small compared to the total trophic flows within the home range of the large predator (Cousins 1990). Acknowledging these issues of space, Polis et al (1996) argued that progress toward the next phase of food web studies would require addressing spatial and temporal processes. Here, we present a conceptual framework with some nuclei about the role of space in food web ecology. Although we primarily address spatial aspects, this framework is linked to a more general concept of spatio-temporal scales of ecological research.
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| 5. |
- Escudier, Bernard, et al.
(författare)
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Phase II study of sunitinib administered in a continuous once-daily dosing regimen in patients with cytokine-refractory metastatic renal cell carcinoma.
- 2009
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 27:25, s. 4068-4075
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Sunitinib has demonstrated antitumor activity in metastatic renal cell carcinoma (mRCC) when given at 50 mg/d on a 4-weeks-on 2-weeks-off regimen. Herein, we report results of an open-label, multicenter phase II mRCC study of sunitinib administered on a continuous once-daily dosing regimen. PATIENTS AND METHODS: Eligibility criteria included histologically proven mRCC with measurable disease, failure of one prior cytokine regimen, and good performance status. Patients were randomly assigned to a sunitinib starting dose of 37.5 mg/d in the morning (AM) or evening (PM). RECIST-defined objective response rate (ORR) was the primary end point. Secondary end points included progression-free survival (PFS), overall survival (OS), adverse events (AEs), and quality-of-life measures. RESULTS: One hundred seven patients were randomly assigned to AM (n = 54) or PM (n = 53) dosing and on study for a median 8.3 months. Eighty-three patients discontinued, 65 due to disease progression and 16 because of AEs; two patients withdrew consent. Dosing was reduced to 25 mg/d in 46 patients (43%) due to grade 3/4 AEs. The most common grade 3 treatment-related AEs were asthenia/fatigue (16%), diarrhea (11%), hypertension (11%), hand-foot syndrome (9%), and anorexia (8%). ORR was 20% with a 7.2-month median response duration. Median PFS and OS were 8.2 and 19.8 months, respectively, at median follow-up of 26.4 months. Efficacy, tolerability, and quality-of-life results were similar between patients dosed in the AM or PM. CONCLUSION: Sunitinib 37.5 mg, administered on a continuous once-daily dosing regimen, has a manageable safety profile as second-line mRCC therapy, providing flexible dosing, which can be explored in combination studies.
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| 6. |
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| 7. |
- Hines, Jes, et al.
(författare)
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Towards an integration of biodiversity-ecosystem functioning and food web theory to evaluate relationships between multiple ecosystem services
- 2015
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Ingår i: Advances in Ecological Research. - : Elsevier. - 0065-2504. ; 53, s. 161-199
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Tidskriftsartikel (refereegranskat)abstract
- Ecosystem responses to changes in species diversity are often studied individually. However, changes in species diversity can simultaneously influence multiple interdependent ecosystem functions. Therefore, an important challenge is to determine when and how changes in species diversity that influence one function will also drive changes in other functions. By providing the underlying structure of species interactions, ecological networks can quantify connections between biodiversity and multiple ecosystem functions. Here, we review parallels in the conceptual development of biodiversity- ecosystem functioning (BEF) and food web theory (FWT) research. Subsequently, we evaluate three common principles that unite these two research areas by explaining the patterns, concentrations, and direction of the flux of nutrients and energy through the species in diverse interaction webs. We give examples of combined BEF-FWT approaches that can be used to identify vulnerable species and habitats and to evaluate links that drive trade-offs between multiple ecosystems functions. These combined approaches reflect promising trends towards better management of biodiversity in landscapes that provide essential ecosystem services supporting human well-being.
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| 8. |
- Iles, Mark M., et al.
(författare)
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A variant in FTO shows association with melanoma risk not due to BMI
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:4, s. 428-432
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Tidskriftsartikel (refereegranskat)abstract
- We report the results of an association study of melanoma that is based on the genome-wide imputation of the genotypes of 1,353 cases and 3,566 controls of European origin conducted by the GenoMEL consortium. This revealed an association between several SNPs in intron 8 of the FTO gene, including rs16953002, which replicated using 12,313 cases and 55,667 controls of European ancestry from Europe, the USA and Australia (combined P = 3.6 x 10(-12), per-allele odds ratio for allele A = 1.16). In addition to identifying a new melanomasusceptibility locus, this is to our knowledge the first study to identify and replicate an association with SNPs in FTO not related to body mass index (BMI). These SNPs are not in intron 1 (the BMI-related region) and exhibit no association with BMI. This suggests FTO's function may be broader than the existing paradigm that FTO variants influence multiple traits only through their associations with BMI and obesity.
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| 9. |
- Korchynska, Solomiia, et al.
(författare)
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Life-long impairment of glucose homeostasis upon prenatal exposure to psychostimulants
- 2020
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Ingår i: EMBO Journal. - : EMBO. - 1460-2075 .- 0261-4189. ; 39:1
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Tidskriftsartikel (refereegranskat)abstract
- Maternal drug abuse during pregnancy is a rapidly escalating societal problem. Psychostimulants, including amphetamine, cocaine, and methamphetamine, are amongst the illicit drugs most commonly consumed by pregnant women. Neuropharmacology concepts posit that psychostimulants affect monoamine signaling in the nervous system by their affinities to neurotransmitter reuptake and vesicular transporters to heighten neurotransmitter availability extracellularly. Exacerbated dopamine signaling is particularly considered as a key determinant of psychostimulant action. Much less is known about possible adverse effects of these drugs on peripheral organs, and if in utero exposure induces lifelong pathologies. Here, we addressed this question by combining human RNA-seq data with cellular and mouse models of neuroendocrine development. We show that episodic maternal exposure to psychostimulants during pregnancy coincident with the intrauterine specification of pancreatic β cells permanently impairs their ability of insulin production, leading to glucose intolerance in adult female but not male offspring. We link psychostimulant action specifically to serotonin signaling and implicate the sex-specific epigenetic reprogramming of serotonin-related gene regulatory networks upstream from the transcription factor Pet1/Fev as determinants of reduced insulin production.
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| 10. |
- Mulder, Jacob, et al.
(författare)
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New Reference Materials, Analytical Procedures and Data Reduction Strategies for Sr Isotope Measurements in Geological Materials by LA‐MC‐ICP‐MS
- 2023
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Ingår i: Geostandards and Geoanalytical Research. - : Wiley. - 1639-4488 .- 1751-908X. ; 47:2, s. 311-336
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Tidskriftsartikel (refereegranskat)abstract
- Laser ablation multi-collector mass spectrometry (LA-MC-ICP-MS) has emerged as the technique of choice for in situ measurements of Sr isotopes in geological minerals. However, the method poses analytical challenges and there is no widely adopted standardised approach to collecting these data or correcting the numerous potential isobaric inferences. Here, we outline practical analytical procedures and data reduction strategies to help establish a consistent framework for collecting and correcting Sr isotope measurements in geological materials by LA-MC-ICP-MS. We characterise a new set of plagioclase reference materials, which are available for distribution to the community, and present a new data reduction scheme for the Iolite software package to correct isobaric interferences for different materials and analytical conditions. Our tests show that a combination of Kr-baseline subtraction, Rb-peak-stripping using βRb derived from a bracketing glass reference material, and a CaCa or CaAr correction for plagioclase and CaCa or CaAr + REE2+ correction for rock glasses, yields the most accurate and precise 87Sr/86Sr measurements for these materials. Using the analytical and correction procedures outlined herein, spot analyses using a beam diameter of 100 μm or rastering with a 50–65 μm diameter beam can readily achieve < 100 ppm 2SE repeatability ("internal") precision for 87Sr/86Sr measurements for materials with < 1000 μg g-1 Sr.
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