| 1. |
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| 2. |
- Engert, Andreas, et al.
(författare)
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The European Hematology Association Roadmap for European Hematology Research : a consensus document
- 2016
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Ingår i: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
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Tidskriftsartikel (refereegranskat)abstract
- The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
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| 3. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 4. |
- Azzouzi, Abdel Rahmène, et al.
(författare)
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Padeliporfin vascular-targeted photodynamic therapy versus active surveillance in men with low-risk prostate cancer (CLIN1001 PCM301) : An open-label, phase 3, randomised controlled trial
- 2017
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Ingår i: The Lancet Oncology. - 1470-2045. ; 18:2, s. 181-191
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Tidskriftsartikel (refereegranskat)abstract
- Background: Vascular-targeted photodynamic therapy, a novel tissue-preserving treatment for low-risk prostate cancer, has shown favourable safety and efficacy results in single-arm phase 1 and 2 studies. We compared this treatment with the standard of care, active surveillance, in men with low-risk prostate cancer in a phase 3 trial. Methods: This randomised controlled trial was done in 47 European university centres and community hospitals. Men with low-risk, localised prostate cancer (Gleason pattern 3) who had received no previous treatment were randomly assigned (1:1) to vascular-targeted photodynamic therapy (4 mg/kg padeliporfin intravenously over 10 min and optical fibres inserted into the prostate to cover the desired treatment zone and subsequent activation by laser light 753 nm with a fixed power of 150 mW/cm for 22 min 15 s) or active surveillance. Randomisation was done by a web-based allocation system stratified by centre with balanced blocks of two or four patients. Best practice for active surveillance at the time of study design was followed (ie, biopsy at 12-month intervals and prostate-specific antigen measurement and digital rectal examination at 3-month intervals). The co-primary endpoints were treatment failure (histological progression of cancer from low to moderate or high risk or death during 24 months' follow-up) and absence of definite cancer (absence of any histology result definitely positive for cancer at month 24). Analysis was by intention to treat. Treatment was open-label, but investigators assessing primary efficacy outcomes were masked to treatment allocation. This trial is registered with . ClinicalTrials.gov, number . NCT01310894. Findings: Between March 8, 2011, and April 30, 2013, we randomly assigned 206 patients to vascular-targeted photodynamic therapy and 207 patients to active surveillance. Median follow-up was 24 months (IQR 24-25). The proportion of participants who had disease progression at month 24 was 58 (28%) of 206 in the vascular-targeted photodynamic therapy group compared with 120 (58%) of 207 in the active surveillance group (adjusted hazard ratio 0·34, 95% CI 0·24-0·46; p<0·0001). 101 (49%) men in the vascular-targeted photodynamic therapy group had a negative prostate biopsy result at 24 months post treatment compared with 28 (14%) men in the active surveillance group (adjusted risk ratio 3·67, 95% CI 2·53-5·33; p<0·0001). Vascular-targeted photodynamic therapy was well tolerated. The most common grade 3-4 adverse events were prostatitis (three [2%] in the vascular-targeted photodynamic therapy group . vs one [<1%] in the active surveillance group), acute urinary retention (three [2%] . vs one [<1%]) and erectile dysfunction (two [1%] . vs three [1%]). The most common serious adverse event in the vascular-targeted photodynamic therapy group was retention of urine (15 patients; severe in three); this event resolved within 2 months in all patients. The most common serious adverse event in the active surveillance group was myocardial infarction (three patients). Interpretation: Padeliporfin vascular-targeted photodynamic therapy is a safe, effective treatment for low-risk, localised prostate cancer. This treatment might allow more men to consider a tissue-preserving approach and defer or avoid radical therapy. Funding: Steba Biotech.
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| 5. |
- Berntsson, Annika, et al.
(författare)
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Late Holocene high precipitation events recorded in lake sediments and catchment geomorphology, Lake Vuoksjavratje, NW Sweden
- 2015
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Ingår i: Boreas. - : Wiley. - 0300-9483 .- 1502-3885. ; 44:4, s. 676-692
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we show the potential of combining multi-proxy analysis of lake sediments with catchment geomorphology to better understand palaeoenvironmental changes. Previous studies have suggested that alpine lakes in N Sweden may be highly sensitive to variations in catchment erosion and precipitation, and that this sensitivity may influence ecologically based reconstructions of past temperature changes. We analysed lake sediments covering the last 5100 years from the alpine Lake Vuoksjavratje in NW Sweden in order to identify different erosional regimes in the lake catchment, sediment sources and lake sedimentary processes, which ultimately affect the palaeoecological record. The measured proxies include elemental geochemistry from XRF core scanning, grain size, sediment accumulation rates, fraction of terrestrial organic carbon and geomorphological mapping, supported by previously published chironomid and total organic carbon data. From the integrated results we identified time intervals when increased intensity of precipitation altered sedimentation and lake catchment erosional processes. The most prominent event occurred c. 2900 cal. a BP and is interpreted to be the result of excessive precipitation, possibly related to the climatic shift towards cooler and wetter conditions referred to as the 2.8 ka event.
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| 6. |
- Berntsson, Annika, 1979-, et al.
(författare)
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Late Holocene high precipitation events recorded in lake sediments and catchment geomorphology, Lake Vuoksjávrátje, NW Sweden
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In this paper, we highlight the importance of combining multi-proxy analysis of lake sediments with associated catchment geomorphology to better understand the late Holocene palaeoenvironmental evolution in a high latitude Alpine lake in N Sweden. Previous studies have suggested that such lakes may be highly sensitive to variations in catchment erosion and variations in precipitation, and that this sensitivity may influence ecologically-based reconstructions of past temperature changes. Here we have analysed lake sediments covering the last 5100 years from Lake Vuoksjávrátje in NW Sweden to identify different erosional regimes in the lake catchment and to identify sediment sources and lake sedimentary processes, which ultimately affect the palaeoecological record. Methods that were used include XRF core scanning, grain size analysis and geomorphological mapping, supported by previously published chironomid, total organic carbon and carbon/nitrogen data. From the integrated results we identify time intervals when increased amounts/intensity of precipitation altered sedimentation and lake catchment erosional processes. The most prominent event in our record occurred between 3090 and 2750 cal. a BP and is interpreted to be the result of excessive precipitation in relation to the 2.8 ka event. By combining the multi-proxy analysis of a lake sediment core with a detailed catchment characterisation it is possible to reach a better understanding of the processes active within the lake catchment, the factors governing the erosional regimes and the way these are recorded in lake sediments. For future palaeoclimatological research based on lake sediments we recommend increasing the integration of catchment geomorphology, sedimentology and palaeoecology.
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| 7. |
- Bertrand, Lionel, et al.
(författare)
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A multiscale analysis of a fracture pattern in granite : A case study of the Tamariu granite, Catalunya, Spain
- 2015
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Ingår i: Journal of Structural Geology. - : Elsevier BV. - 0191-8141 .- 1873-1201. ; 78, s. 52-66
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Tidskriftsartikel (refereegranskat)abstract
- The in-depth investigation of fractured reservoirs is mainly limited to geophysical data that is in 3D and mostly on the scale of hundred meters to several kilometers or boreholes data that is in 1D and at meter to lower scale. The study of outcropping analogues of buried reservoirs is therefore a key tool for the characterization of the fault and fracture network at the reservoir scale. Tamariu granite has been the subject of this study with the aim to analyse faults and fractures from seismic to borehole scale. With the combination of satellite picture at different resolution and field study, we perform a statistical analysis focused of the length and orientation from infra centimeter crack to hundred kilometer length fault. On the whole range of scale studied, i.e. on 7 orders of magnitude, we have defined a length distribution following a power-law with an exponent a = -2. On the contrary to the length that can be modelled with a unique law, the orientation data shows a variation depending on the scale of observation: as the fault and fracture sets are suitable from the regional faults to the centimeter crack, the proportion of the sets varies at each scale of observation.
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| 8. |
- Bertrand, Philip, et al.
(författare)
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Feeding at the front line : interannual variation in the use of glacier fronts by foraging black-legged kittiwakes
- 2021
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Ingår i: Marine Ecology Progress Series. - : Inter-Research Science Center. - 0171-8630 .- 1616-1599. ; 677, s. 197-208
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Tidskriftsartikel (refereegranskat)abstract
- Tidewater glacier fronts can represent important foraging areas for Arctic predators. Their ecological importance is likely to change in a warmer Arctic. Their profitability and use by consumers are expected to vary in time, but the underlying mechanisms driving such variation remain poorly known. The subglacial plume, originating from meltwater discharge, is responsible for the entrainment and transport of zooplankton to the surface, making them more readily available for surface-feeding seabirds. Both discharge and zooplankton abundance are known to fluctuate in time and are thus expected to modulate the foraging profitability of glacier fronts. This study tested the predictions that annual use of glacier fronts by black-legged kittiwakes Rissa tridactyla is positively related to the average glacier discharge and prey biomass in the fjord. To do this, we combined a multiyear dataset of environmental drivers and GPS tracks of birds in Kongsfjorden, Svalbard. Our results confirmed the interannual variation in the use of glacier fronts by kittiwakes; however, contrary to our predictions, these variations were negatively correlated to both glacier discharge and zooplankton abundance. These apparent negative relationships likely reflect non-linear effects and complex interactions between local and regional environmental factors that affect the relative profitability of glacier fronts as foraging areas. Despite their high spatial predictability, glacier fronts may not offer consistent foraging opportunities for marine predators over time.
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| 9. |
- Bertrand, Sebastien, et al.
(författare)
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Inorganic geochemistry of lake sediments : a review of analytical techniques and guidelines for data interpretation
- 2024
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Ingår i: Earth-Science Reviews. - : Elsevier. - 0012-8252 .- 1872-6828. ; 249
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Forskningsöversikt (refereegranskat)abstract
- Inorganic geochemistry is a powerful tool in paleolimnology. It has become one of the most commonly used techniques to analyze lake sediments, particularly due to the development and increasing availability of XRF core scanners during the last two decades. It allows for the reconstruction of the continuous processes that occur in lakes and their watersheds, and it is ideally suited to identify event deposits. How earth surface processes and limnological conditions are recorded in the inorganic geochemical composition of lake sediments is, however, relatively complex. Here, we review the main techniques used for the inorganic geochemical analysis of lake sediments and we offer guidance on sample preparation and instrument selection. We then summarize the best practices to process and interpret bulk inorganic geochemical data. In particular, we emphasize that log-ratio transformation is critical for the rigorous statistical analysis of geochemical datasets, whether they are obtained by XRF core scanning or more traditional techniques. In addition, we show that accurately interpreting inorganic geochemical data requires a sound understanding of the main components of the sediment (organic matter, biogenic silica, carbonates, lithogenic particles) and mineral assemblages. Finally, we provide a series of examples illustrating the potential and limits of inorganic geochemistry in paleolimnology. Although the examples presented in this paper focus on lake and fjord sediments, the principles presented here also apply to other sedimentary environments.
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| 10. |
- Ekanem, Emmanuel, et al.
(författare)
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Safety of pulsed field ablation in more than 17,000 patients with atrial fibrillation in the MANIFEST-17K study
- 2024
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Ingår i: Nature Medicine. - : NATURE PORTFOLIO. - 1078-8956 .- 1546-170X.
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Tidskriftsartikel (refereegranskat)abstract
- Pulsed field ablation (PFA) is an emerging technology for the treatment of atrial fibrillation (AF), for which pre-clinical and early-stage clinical data are suggestive of some degree of preferentiality to myocardial tissue ablation without damage to adjacent structures. Here in the MANIFEST-17K study we assessed the safety of PFA by studying the post-approval use of this treatment modality. Of the 116 centers performing post-approval PFA with a pentaspline catheter, data were received from 106 centers (91.4% participation) regarding 17,642 patients undergoing PFA (mean age 64, 34.7% female, 57.8% paroxysmal AF and 35.2% persistent AF). No esophageal complications, pulmonary vein stenosis or persistent phrenic palsy was reported (transient palsy was reported in 0.06% of patients; 11 of 17,642). Major complications, reported for similar to 1% of patients (173 of 17,642), were pericardial tamponade (0.36%; 63 of 17,642) and vascular events (0.30%; 53 of 17,642). Stroke was rare (0.12%; 22 of 17,642) and death was even rarer (0.03%; 5 of 17,642). Unexpected complications of PFA were coronary arterial spasm in 0.14% of patients (25 of 17,642) and hemolysis-related acute renal failure necessitating hemodialysis in 0.03% of patients (5 of 17,642). Taken together, these data indicate that PFA demonstrates a favorable safety profile by avoiding much of the collateral damage seen with conventional thermal ablation. PFA has the potential to be transformative for the management of patients with AF.
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