| 11. |
- Njolstad, T. S., et al.
(författare)
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DNA ploidy in curettage specimens identifies high-risk patients and lymph node metastasis in endometrial cancer
- 2015
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 112:10, s. 1656-1664
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Tidskriftsartikel (refereegranskat)abstract
- Background: Preoperative risk stratification is essential in tailoring endometrial cancer treatment, and biomarkers predicting lymph node metastasis and aggressive disease are aspired in clinical practice. DNA ploidy assessment in hysterectomy specimens is a well-established prognostic marker. DNA ploidy assessment in preoperative curettage specimens is less studied, and in particular in relation to the occurrence of lymph node metastasis. Methods: Curettage image cytometry DNA ploidy in relation to established clinicopathological variables and outcome was investigated in 785 endometrial carcinoma patients prospectively included in the MoMaTEC multicentre trial. Results: Diploid curettage status was found in 72.0%, whereas 28.0% were non-diploid. Non-diploid status significantly correlated with traditional aggressive postoperative clinicopathological features, and was an independent predictor of lymph node metastasis among FIGO stage I-III patients in multivariate analysis (OR 1.94, P = 0.033). Non-diploid status was related to shorter disease-specific survival (5-year DSS of 74.4% vs 88.8% for diploid curettage, P<0.001). When stratifying by FIGO stage and lymph node status, the prognostic effect remained. However, in multivariate regression analysis, preoperative histological risk classification was a stronger predictor of DSS than DNA ploidy. Conclusions: Non-diploid curettage is significantly associated with aggressive clinicopathological phenotype, lymph node metastasis, and poor survival in endometrial cancer. The prognostic effect was also observed among subgroups with (presumably) less aggressive traits, such as low FIGO stage and negative lymph node status. Our results indicate curettage DNA ploidy as a possible supplement to existing parameters used to tailor surgical treatment. ELER VM, 1991, CANCER, V67, P3093
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| 12. |
- Woods, P. J., et al.
(författare)
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A review of adaptation options in fisheries management to support resilience and transition under socio-ecological change
- 2022
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Ingår i: ICES Journal of Marine Science. - : Oxford University Press (OUP). - 1054-3139 .- 1095-9289. ; 79:2, s. 463-479
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Forskningsöversikt (refereegranskat)abstract
- Social-ecological systems dependent on fisheries must be resilient or adapt to remain viable in the face of change. Here, we identified possible interventions (termed “adaptation options”) from published literature, aimed at supporting social or ecological resilience and/or aiding adaptation to changes induced by environmental or social stressors. Our searches centered on nations/regions across North America, Europe, and the South Pacific, encompassing fisheries literature with and without a climate change focus, to compare how, when, and by whom interventions are currently or potentially implemented. We expected that adaptation options within a climate change context would have a greater focus on enhancing social resilience due to a connection with climate change adaptation assessment methodology. Instead, we found a greater focus on ecological resilience, likely indicating a focus on management adaptation. This pattern, along with the more extensive use of social adaptation options responsively and outside the context of climate change, along with an importance in bottom-up influences in implementing them, suggests a general lack of centralized planning and organization with regards to adaptation of stakeholders. Determining how adaptation options are created, chosen, and implemented is a crucial step within or external to ecosystem-based management, especially if planned stakeholder adaption is the goal.
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| 13. |
- Messias, M. J, et al.
(författare)
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The Greenland Sea tracer experiment 1996–2002: Horizontal mixing and transport of Greenland Sea Intermediate Water
- 2008
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Ingår i: Progress In Oceanography. - : Elsevier BV. - 0079-6611. ; 78:1, s. 85-105
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Tidskriftsartikel (refereegranskat)abstract
- In summer 1996, a tracer release experiment using sulphur hexafluoride (SF6) was launched in the intermediate-depth waters of the central Greenland Sea (GS), to study the mixing and ventilation processes in the region and its role in the northern limb of the Atlantic overturning circulation. Here we describe the hydrographic context of the experiment, the methods adopted and the results from the monitoring of the horizontal tracer spread for the 1996–2002 period documented by 10 shipboard surveys. The tracer marked “Greenland Sea Arctic Intermediate Water” (GSAIW). This was redistributed in the gyre by variable winter convection penetrating only to mid-depths, reaching at most 1800 m depth during the strongest event observed in 2002. For the first 18 months, the tracer remained mainly in the Greenland Sea. Vigorous horizontal mixing within the Greenland Sea gyre and a tight circulation of the gyre interacting slowly with the other basins under strong topographic influences were identified. We use the tracer distributions to derive the horizontal shear at the scale of the Greenland Sea gyre, and rates of horizontal mixing at 10 and 300 km scales. Mixing rates at small scale are high, several times those observed at comparable depths at lower latitudes. Horizontal stirring at the sub-gyre scale is mediated by numerous and vigorous eddies. Evidence obtained during the tracer release suggests that these play an important role in mixing water masses to form the intermediate waters of the central Greenland Sea. By year two, the tracer had entered the surrounding current systems at intermediate depths and small concentrations were in proximity to the overflows into the North Atlantic. After 3 years, the tracer had spread over the Nordic Seas basins. Finally by year six, an intensive large survey provided an overall synoptic documentation of the spreading of the tagged GSAIW in the Nordic Seas. A circulation scheme of the tagged water originating from the centre of the GS is deduced from the horizontal spread of the tracer. We present this circulation and evaluate the transport budgets of the tracer between the GS and the surroundings basins. The overall residence time for the tagged GSAIW in the Greenland Sea was about 2.5 years. We infer an export of intermediate water of GSAIW from the GS of 1 to 1.85 Sv (1 Sv = 106 m3 s−1) for the period from September 1998 to June 2002 based on the evolution of the amount of tracer leaving the GS gyre. There is strong exchange between the Greenland Sea and Arctic Ocean via Fram Strait, but the contribution of the Greenland Sea to the Denmark Strait and Iceland Scotland overflows is modest, probably not exceeding 6% during the period under study.
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| 14. |
- Bonebrake, Timothy C., et al.
(författare)
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Managing consequences of climate-driven species redistribution requires integration of ecology, conservation and social science
- 2018
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Ingår i: Biological Reviews. - : Wiley-Blackwell Publishing Inc.. - 1464-7931 .- 1469-185X. ; 93:1, s. 284-305
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Forskningsöversikt (refereegranskat)abstract
- Climate change is driving a pervasive global redistribution of the planet's species. Species redistribution poses new questions for the study of ecosystems, conservation science and human societies that require a coordinated and integrated approach. Here we review recent progress, key gaps and strategic directions in this nascent research area, emphasising emerging themes in species redistribution biology, the importance of understanding underlying drivers and the need to anticipate novel outcomes of changes in species ranges. We highlight that species redistribution has manifest implications across multiple temporal and spatial scales and from genes to ecosystems. Understanding range shifts from ecological, physiological, genetic and biogeographical perspectives is essential for informing changing paradigms in conservation science and for designing conservation strategies that incorporate changing population connectivity and advance adaptation to climate change. Species redistributions present challenges for human well-being, environmental management and sustainable development. By synthesising recent approaches, theories and tools, our review establishes an interdisciplinary foundation for the development of future research on species redistribution. Specifically, we demonstrate how ecological, conservation and social research on species redistribution can best be achieved by working across disciplinary boundaries to develop and implement solutions to climate change challenges. Future studies should therefore integrate existing and complementary scientific frameworks while incorporating social science and human-centred approaches. Finally, we emphasise that the best science will not be useful unless more scientists engage with managers, policy makers and the public to develop responsible and socially acceptable options for the global challenges arising from species redistributions.
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| 15. |
- Jongsma Wallin, Helen, et al.
(författare)
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Exogenous NT-3 and NGF differentially modulate PACAP expression in adult sensory neurons, suggesting distinct roles in injury and inflammation
- 2001
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 14:2, s. 267-282
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Tidskriftsartikel (refereegranskat)abstract
- Expression of pituitary adenylate cyclase-activating polypeptide in sensory neurons varies with injury or inflammation. The neurotrophins NGF and NT-3 are profound regulators of neuronal peptidergic phenotype in intact and injured sensory neurons. This study examined their potential for modulation of PACAP expression in adult rat with intact and injured L4-L6 spinal nerves with or without immediate or delayed intrathecal infusion of NT-3 or NGF. Results indicate that in L5 DRG, few trkC neurons express high levels of PACAP mRNA in the intact state, but many do following injury. The elevated expression in injured neurons is mitigated by NT-3 infusion, suggesting a role for NT-3 in returning the 'injured phenotype' back towards an 'Intact phenotype'. NGF dramatically up-regulated PACAP expression in trkA-positive neurons in both intact and injured DRGs, implicating NGF as a positive regulator of PACAP expression in nociceptive neurons. Surprisingly, NT-3 modulates PACAP expression in an antagonistic fashion to NGF in intact neurons, an effect most evident in the trkA neurons not expressing trkC. Both NT-3 and NGF infusion results in decreased detection of PACAP protein in the region of the gracile nuclei, where central axons of the peripherally axotomized large sensory fibers terminate. NGF infusion also greatly increased the amount of PACAP protein detected in the portion of the dorsal horn innervated by small-medium size DRG neurons, while both neurotrophins appear able to prevent the decrease in PACAP expression observed in these afferents with injury. These results provide the first insights into the potential molecules implicated in the complex regulation of PACAP expression in sensory neurons.
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| 16. |
- Pecl, Gretta T., et al.
(författare)
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Biodiversity redistribution under climate change : Impacts on ecosystems and human well-being
- 2017
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 355:6332
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Forskningsöversikt (refereegranskat)abstract
- Distributions of Earth's species are changing at accelerating rates, increasingly driven by human-mediated climate change. Such changes are already altering the composition of ecological communities, but beyond conservation of natural systems, how and why does this matter? We review evidence that climate-driven species redistribution at regional to global scales affects ecosystem functioning, human well-being, and the dynamics of climate change itself. Production of natural resources required for food security, patterns of disease transmission, and processes of carbon sequestration are all altered by changes in species distribution. Consideration of these effects of biodiversity redistribution is critical yet lacking in most mitigation and adaptation strategies, including the United Nation's Sustainable Development Goals.
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| 17. |
- Borgwardt, L., et al.
(författare)
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Alpha-mannosidosis: characterization of CNS pathology and correlation between CNS pathology and cognitive function
- 2016
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Ingår i: Clinical Genetics. - : Wiley. - 0009-9163. ; 89:4, s. 489-494
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Tidskriftsartikel (refereegranskat)abstract
- Alpha-mannosidosis (AM) (OMIM 248500) is a rare lysosomal storage disease. The understanding of the central nervous system (CNS) pathology is limited. This study is the first describing the CNS pathology and the correlation between the CNS pathology and intellectual disabilities in human AM. Thirty-four patients, aged 6-35 years, with AM were included. Data from 13 healthy controls were included in the analysis of the magnetic resonance spectroscopy (MRS). Measurements of CNS neurodegeneration biomarkers in cerebrospinal fluid (CSF), CSF-oligosaccharides, and performance of cerebral magnetic resonance imaging (MRI) and MRS were carried out. On MRI, 5 of 10 patients had occipital white matter (WM) signal abnormalities, and 6 of 10 patients had age-inappropriate myelination. MRS demonstrated significantly elevated mannose complex in gray matter and WM. We found elevated concentrations of tau-protein, glial fibrillary acidic protein and neurofilament light protein in 97 patients, 74% and 41% of CSF samples, respectively. A negative correlation between CSF-biomarkers and cognitive function and CSF-oligosaccharides and cognitive function was found. The combination of MRS/MRI changes, elevated concentrations of CSF-biomarkers and CSF-oligosaccharides suggests gliosis and reduced myelination, as part of the CNS pathology in AM. Our data demonstrate early neuropathological changes, which may be taken into consideration when planning initiation of treatment.
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| 18. |
- Chen, H.Y., et al.
(författare)
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Dyslipidemia, inflammation, calcification, and adiposity in aortic stenosis: a genome-wide study
- 2023
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 44:21, s. 1927-1939
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Tidskriftsartikel (refereegranskat)abstract
- Aims Although highly heritable, the genetic etiology of calcific aortic stenosis (AS) remains incompletely understood. The aim of this study was to discover novel genetic contributors to AS and to integrate functional, expression, and cross-phenotype data to identify mechanisms of AS. Methods and results A genome-wide meta-analysis of 11.6 million variants in 10 cohorts involving 653 867 European ancestry participants (13 765 cases) was performed. Seventeen loci were associated with AS at P ≤ 5 × 10−8, of which 15 replicated in an independent cohort of 90 828 participants (7111 cases), including CELSR2–SORT1, NLRP6, and SMC2. A genetic risk score comprised of the index variants was associated with AS [odds ratio (OR) per standard deviation, 1.31; 95% confidence interval (CI), 1.26–1.35; P = 2.7 × 10−51] and aortic valve calcium (OR per standard deviation, 1.22; 95% CI, 1.08–1.37; P = 1.4 × 10−3), after adjustment for known risk factors. A phenome-wide association study indicated multiple associations with coronary artery disease, apolipoprotein B, and triglycerides. Mendelian randomization supported a causal role for apolipoprotein B-containing lipoprotein particles in AS (OR per g/L of apolipoprotein B, 3.85; 95% CI, 2.90–5.12; P = 2.1 × 10−20) and replicated previous findings of causality for lipoprotein(a) (OR per natural logarithm, 1.20; 95% CI, 1.17–1.23; P = 4.8 × 10−73) and body mass index (OR per kg/m2, 1.07; 95% CI, 1.05–1.9; P = 1.9 × 10−12). Colocalization analyses using the GTEx database identified a role for differential expression of the genes LPA, SORT1, ACTR2, NOTCH4, IL6R, and FADS. Conclusion Dyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS, implicating novel treatments and prevention strategies. © The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.
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| 19. |
- Duvetorp, Albert, et al.
(författare)
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Quality of life and contact with healthcare systems among patients with psoriasis and psoriatic arthritis: results from the NORdic PAtient survey of Psoriasis and Psoriatic arthritis (NORPAPP)
- 2019
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Ingår i: Archives of Dermatological Research. - : SPRINGER. - 0340-3696 .- 1432-069X. ; 311:5, s. 351-360
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Tidskriftsartikel (refereegranskat)abstract
- Psoriasis (skin psoriasis, PsO) is a chronic inflammatory condition. In about one-third of cases, the joints are affected (psoriatic arthritis, PsA). Both conditions, especially PsA, profoundly impact patients health-related quality of life (HRQoL). To describe the impact of psoriasis on HRQoL and patients contact with the healthcare system in Sweden, Denmark, and Norway, the NORdic PAtient survey of Psoriasis and Psoriatic arthritis (NORPAPP) asked 22,050 adults randomly selected in Sweden, Denmark and Norway if they had psoriasis. 1264 individuals who reported physician-diagnosed PsO/PsA were invited to the full survey; 1221 responded (74.6% diagnosed with PsO alone; 25.4% with PsA +/- PsO). Respondents with PsA most frequently consulted a rheumatologist; however, 14.3% had never seen a rheumatologist. Respondents with PsO alone most frequently consulted a general practitioner and 10.7% had never seen a dermatologist (although those with severe symptoms visited dermatologists more often). Negative impacts on HRQoL were reported by 38.1% of respondents with PsO [mostly limitations on clothing (22.6%), sleep disorders (16%), and depression/anxiety (16%)] and by 73% of respondents with PsA [mostly limitations on clothing (41.8%), sports/leisure (44.0%), or daily routine (45.1%) and sleeping disorders]. Absence from work/education was more common with PsA +/- PsO (51.9%) than PsO alone (15.1%). In this survey in Sweden, Denmark, and Norway, the impact of psoriasis on the respondents HRQoL was profound and was greater for PsA than for PsO, as was sickness absence. Sleeping disorders and depression were common and should not be overlooked.
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| 20. |
- Geremia, Nicole M., et al.
(författare)
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Endogenous BDNF regulates induction of intrinsic neuronal growth programs in injured sensory neurons
- 2010
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 223:1, s. 128-142
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Tidskriftsartikel (refereegranskat)abstract
- Identification of the molecule(s) that globally induce a robust regenerative state in sensory neurons following peripheral nerve injury remains elusive. A potential candidate is brain-derived neurotrophic factor (BDNF), the sole neurotrophin upregulated in sensory neurons after peripheral nerve injury. Here we tested the hypothesis that BDNF plays a critical role in the regenerative response of mature rat sensory neurons following peripheral nerve lesion. Neutralization of endogenous BDNF was performed by infusing BDNF antibodies intrathecally via a mini-osmotic pump for 3 days at the level of the fifth lumbar dorsal root ganglion, immediately following unilateral spinal nerve injury. This resulted in decreased expression of the injury/regeneration-associated genes growth-associated protein-43 and T alpha 1 tubulin in the injured sensory neurons as compared to injury plus control IgG infused or injury alone animals. Similar results were observed following inhibition of BDNF expression by intrathecal delivery of small interfering RNAs (siRNA) targeting BDNF starting 3 days prior to injury. The reduced injury/regeneration-associated gene expression correlated with a significantly reduced intrinsic capacity of these neurons to extend neurites when assayed in vitro. In contrast, delayed infusion of BDNF antibody for 3 days beginning 1 week post-lesion had no discernible influence on the elevated expression of these regeneration-associated markers. These results support an important role for endogenous BDNF in induction of the cell body response in injured sensory neurons and their intrinsic ability to extend neurites, but BDNF does not appear to be necessary for maintaining the response once it is induced. (C) 2009 Elsevier Inc. All rights reserved.
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