| 1. |
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| 2. |
- Giasson, M-A, et al.
(författare)
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Soil respiration in a northeastern US temperate forest : a 22-year synthesis
- 2013
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Ingår i: Ecosphere. - 2150-8925 .- 2150-8925. ; 4:11, s. UNSP 140-
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Tidskriftsartikel (refereegranskat)abstract
- To better understand how forest management, phenology, vegetation type, and actual and simulated climatic change affect seasonal and inter-annual variations in soil respiration (R-s), we analyzed more than 100,000 individual measurements of soil respiration from 23 studies conducted over 22 years at the Harvard Forest in Petersham, Massachusetts, USA. We also used 24 site-years of eddy-covariance measurements from two Harvard Forest sites to examine the relationship between soil and ecosystem respiration (R-e). R-s was highly variable at all spatial (respiration collar to forest stand) and temporal (minutes to years) scales of measurement. The response of R-s to experimental manipulations mimicking aspects of global change or aimed at partitioning R-s into component fluxes ranged from similar to 70% to +52%. The response appears to arise from variations in substrate availability induced by changes in the size of soil C pools and of belowground C fluxes or in environmental conditions. In some cases (e.g., logging, warming), the effect of experimental manipulations on R-s was transient, but in other cases the time series were not long enough to rule out long-term changes in respiration rates. Inter-annual variations in weather and phenology induced variation among annual R-s estimates of a magnitude similar to that of other drivers of global change (i.e., invasive insects, forest management practices, N deposition). At both eddy-covariance sites, aboveground respiration dominated R-e early in the growing season, whereas belowground respiration dominated later. Unusual aboveground respiration patterns-high apparent rates of respiration during winter and very low rates in mid-to-late summer-at the Environmental Measurement Site suggest either bias in R-s and R-e estimates caused by differences in the spatial scale of processes influencing fluxes, or that additional research on the hard-to-measure fluxes (e.g., wintertime R-s, unaccounted losses of CO2 from eddy covariance sites), daytime and nighttime canopy respiration and its impacts on estimates of R-e, and independent measurements of flux partitioning (e.g., aboveground plant respiration, isotopic partitioning) may yield insight into the unusually high and low fluxes. Overall, however, this data-rich analysis identifies important seasonal and experimental variations in R-s and R-e and in the partitioning of R-e above-vs. belowground.
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| 3. |
- Frank, T.D., et al.
(författare)
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Pace, magnitude, and nature of terrestrial climate change through the end-Permian extinction in southeastern Gondwana
- 2021
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Ingår i: Geology. - : Geological Society of America. - 0091-7613 .- 1943-2682. ; 49:9, s. 1089-1095
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Tidskriftsartikel (refereegranskat)abstract
- Rapid climate change was a major contributor to the end-Permian extinction (EPE). Although well constrained for the marine realm, relatively few records document the pace, nature, and magnitude of climate change across the EPE in terrestrial environments. We generated proxy records for chemical weathering and land surface temperature from continental margin deposits of the high-latitude southeastern margin of Gondwana. Regional climate simulations provide additional context. Results show that Glossopteris forest-mire ecosystems collapsed during a pulse of intense chemical weathering and peak warmth, which capped ∼1 m.y. of gradual warming and intensification of seasonality. Erosion resulting from loss of vegetation was short lived in the low-relief landscape. Earliest Triassic climate was∼10–14 °C warmer than the late Lopingian and landscapes were no longer persistently wet. Aridification, commonly linked to the EPE, developed gradually, facilitating the persistence of refugia for moisture-loving terrestrial groups.
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| 4. |
- Henein, Michael, et al.
(författare)
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European Calcific Coronary Artery Disease (Euro-CCAD) study : the additional value of coronary calcification, to angiography, in investigating angina patients
- 2013
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 34:Supplement: 1, s. 177-177
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and aim: This study is a part of the Euro-CCAD (CalcificCoronary Artery Disease) project, investigating the geographic prevalence of a coronary artery calcium (CAC) score of >400 in patients with no flow-limiting lesions (FLL) as a potential cause for stable angina. With the development of computerized tomographic coronaryangiography (CTCA), assessment of CAC has become less fashionable, although CTCA often fails to determine the exact cause of symptoms in the absence of FLLs.Methods: Data from consecutive symptomatic intermediate risk patients (as defined by guidelines), who had both CA and calcium scoring, were compared between USA and Europe as well as between Europeancountries (Denmark, Germany, France and Spain). No patient had a priorcoronary event, intervention, valve disease or kidney failure.Results: The inclusion criteria were fulfilled in 4,444 patients, (60% males), mean age 59.3 years (SD 11.3 years). The prevalence of FLL was higher in the USA at 53% (983/1851) than in Europe at 34% (870/2593) as a whole, (p<0.001). The FLL prevalence was also different (p<0.001) within Europe: Denmark 16%, Germany 35%, France 46% and Spain 89%. In patients with no FLL, 9% had CAC >400, with no difference in prevalence between the USA and Europe, irrespective of age and gender. However, within Europe the prevalence of patients without FLL and with a CAC score >400 differed: Spain 22%, Germany 13%, France 10% and Denmark 7%. Within the total patient population 22% of those with CAC score >400 had no FLL.Conclusion: Despite the known variability in the current management of symptomatic angina patients at intermediate risk between the USA andEuropean countries, a consistent proportion (nearly 10%) exhibits severe CAC in the absence of flow limiting lesions. The presence of severe CAC could explain their symptoms through compromised coronary flow reserve. These results highlight the potential value of obtaining additional anatomical information by using CAC assessment in symptomatic patients.
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| 5. |
- Henein, Michael Y., et al.
(författare)
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European Calcific Coronary Artery Disease (Euro-CCAD) study : the relationship between coronary calcification and flow limiting lesion in symptomatic patients
- 2013
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 34:Supplement: 1, s. 723-723
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and aim: This study is a part of the Euro-CCAD (CalcificCoronary Artery Disease) project, investigating the geographic prevalence of a coronary artery calcium (CAC) score of >400 in patients with no flow-limiting lesions (FLL) as a potential cause for stable angina. With the development of computerized tomographic coronaryangiography (CTCA), assessment of CAC has become less fashionable, although CTCA often fails to determine the exact cause of symptoms in the absence of FLLs.Methods: Data from consecutive symptomatic intermediate risk patients (as defined by guidelines), who had both CA and calcium scoring, were compared between USA and Europe as well as between Europeancountries (Denmark, Germany, France and Spain). No patient had a priorcoronary event, intervention, valve disease or kidney failure.Results: The inclusion criteria were fulfilled in 4,444 patients, (60% males), mean age 59.3 years (SD 11.3 years). The prevalence of FLL was higher in the USA at 53% (983/1851) than in Europe at 34% (870/2593) as a whole, (p<0.001). The FLL prevalence was also different (p<0.001) within Europe: Denmark 16%, Germany 35%, France 46% and Spain 89%. In patients with no FLL, 9% had CAC >400, with no difference in prevalence between the USA and Europe, irrespective of age and gender. However, within Europe the prevalence of patients without FLL and with a CAC score >400 differed: Spain 22%, Germany 13%, France 10% and Denmark 7%. Within the total patient population 22% of those with CAC score >400 had no FLL.Conclusion: Despite the known variability in the current management of symptomatic angina patients at intermediate risk between the USA andEuropean countries, a consistent proportion (nearly 10%) exhibits severe CAC in the absence of flow limiting lesions. The presence of severe CAC could explain their symptoms through compromised coronary flow reserve. These results highlight the potential value of obtaining additional anatomical information by using CAC assessment in symptomatic patients.
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| 6. |
- Nicoll, Rachel, et al.
(författare)
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Diabetes and male gender are key risk factor predictors of CAC extent : a Euro-CCAD study
- 2016
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims: Although much has been written about the risk factor predictors of CAC extent, few studies have been carried out on symptomatic patients. Similarly, no study has directly compared predictors of CAC extent and zero CAC.Methods: From the European Calcific Coronary Artery Disease (Euro-CCAD) cohort, we retrospectively investigated 6309 symptomatic patients, 62% male, from Denmark, France, Germany, Italy, Spain and USA. All had risk factor assessment and CT scanning for CAC scoring. Results: Among all patients, male gender (β = 1.36, p<0.001) and diabetes (β = 0.47, p<0.001) were the most important risk factors of CAC extent, with age, diabetes (DM), obesity, family history of CAD and number of risk factors also being predictive. Among patients with CAC, DM, hypertension (HT) and dyslipidaemia (DL) were predictors of an increasing CAC score in males and females, with DM being the strongest (p<0.001 for both). These results were echoed in quantile regression, where DM was consistently the most important predictor of CAC extent in every quantile in both males and females. HT and DL were also predictive but to a lesser extent, with HT being predictive in the high CAC quantiles and DL in the low CAC quantiles. Conclusion: In addition to male gender, DM is the most important predictor of CAC extent in both genders.
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| 7. |
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| 8. |
- Nicoll, Rachel, et al.
(författare)
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Gender and age effects on risk factor-based prediction of coronary artery calcium in symptomatic patients : a Euro-CCAD study
- 2016
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Ingår i: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 252, s. 32-39
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: The influence of gender and age on risk factor prediction of coronary artery calcification (CAC) presence in symptomatic patients is unclear.Methods: From the European Calcific Coronary Artery Disease (EURO-CCAD) cohort, we retrospectively investigated 6309 symptomatic patients, 62% male, from Denmark, France, Germany, Italy, Spain and USA. All had risk factor assessment and CT scanning for CAC scoring. Results: The prevalence of CAC among females was lower than among males in all age groups. Using multivariate logistic regression, age, dyslipidaemia, hypertension, diabetes and smoking were independently predictive of CAC presence in both genders. In addition to a progressive increase in CAC with age, the most important predictors of CAC presence were dyslipidaemia and diabetes (β = 0.64 and 0.63 respectively) in males and diabetes (β = 1.08) followed by smoking (β = 0.68) in females; these same risk factors were also important in predicting increasing CAC scores. There was no difference in the predictive ability of diabetes, hypertension and dyslipidaemia in either gender for CAC presence in patients aged <50 and 50-70 years. However, in patients aged >70, only dyslipidaemia predicted CAC presence in males and only smoking and diabetes were predictive in females. Conclusion: In symptomatic patients, there are significant differences in the ability of conventional risk factors to predict CAC presence between genders and between patients aged <70 and ≥70, indicating the important role of age in predicting CAC presence.
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| 9. |
- Nicoll, Rachel, et al.
(författare)
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The coronary calcium score is a more accurate predictor of significant coronary stenosis than conventional risk factors in symptomatic patients : Euro-CCAD study
- 2016
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 207, s. 13-19
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Tidskriftsartikel (refereegranskat)abstract
- Aims: In this retrospective study we assessed the predictive value of the coronary calcium score for significant (>50%) stenosis relative to conventional risk factors. Methods and Results: We investigated 5515 symptomatic patients from Denmark, France, Germany, Italy, Spain and the USA. All had risk factor assessment, computed tomographic coronary angiogram (CTCA) or conventional angiography and a CT scan for coronary artery calcium (CAC) scoring. 1539 (27.9%) patients had significant stenosis, 5.50 of whom had zero CAC. In 5074 patients, multiple binary regression showed the most important predictor of significant stenosis to be male gender (B = 1.07) followed by diabetes mellitus (B = 0.70) smoking, hypercholesterolaemia, hypertension, family history of CAD and age but not obesity. When the log transformed CAC score was included, it became the most powerful predictor (B = 1.25), followed by male gender (B = 0.48), diabetes, smoking, family history and age but hypercholesterolaemia and hypertension lost significance. The CAC score is a more accurate predictor of >50% stenosis than risk factors regardless of the means of assessment of stenosis. The sensitivity of risk factors, CAC score and the combination for prediction of >50% stenosis when measured by conventional angiogram was considerably higher than when assessed by CTCA but the specificity was considerably higher when assessed by CTCA. The accuracy of CTCA for predicting >50% stenosis using the CAC score alone was higher (AUC 0.85) than using a combination of the CAC score and risk factors with conventional angiography (AUC 0.81). Conclusion: In symptomatic patients, the CAC score is a more accurate predictor of significant coronary stenosis than conventional risk factors.
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| 10. |
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| 11. |
- Simone, Roberto, et al.
(författare)
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G-quadruplex-binding small molecules ameliorate C9orf72 FTD/ALS pathology invitro and invivo.
- 2018
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Ingår i: EMBO molecular medicine. - : EMBO. - 1757-4684 .- 1757-4676. ; 10:1, s. 22-31
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Tidskriftsartikel (refereegranskat)abstract
- Intronic GGGGCC repeat expansions in C9orf72 are the most common known cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), which are characterised by degeneration of cortical and motor neurons, respectively. Repeat expansions have been proposed to cause disease by both the repeat RNA forming foci that sequester RNA-binding proteins and through toxic dipeptide repeat proteins generated by repeat-associated non-ATG translation. GGGGCC repeat RNA folds into a G-quadruplex secondary structure, and we investigated whether targeting this structure is a potential therapeutic strategy. We performed a screen that identified three structurally related small molecules that specifically stabilise GGGGCC repeat G-quadruplex RNA We investigated their effect in C9orf72 patient iPSC-derived motor and cortical neurons and show that they significantly reduce RNA foci burden and the levels of dipeptide repeat proteins. Furthermore, they also reduce dipeptide repeat proteins and improve survival invivo, in GGGGCC repeat-expressing Drosophila Therefore, small molecules that target GGGGCC repeat G-quadruplexes can ameliorate the two key pathologies associated with C9orf72 FTD/ALS These data provide proof of principle thattargeting GGGGCC repeat G-quadruplexes has therapeutic potential.
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| 12. |
- Eggens, Veerle Rc, et al.
(författare)
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EXOSC3 mutations in pontocerebellar hypoplasia type 1: novel mutations and genotype-phenotype correlations.
- 2014
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Ingår i: Orphanet journal of rare diseases. - : Springer Science and Business Media LLC. - 1750-1172. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Pontocerebellar hypoplasia (PCH) represents a group of neurodegenerative disorders with prenatal onset. Eight subtypes have been described thus far (PCH1-8) based on clinical and genetic features. Common characteristics include hypoplasia and atrophy of the cerebellum, variable pontine atrophy, and severe mental and motor impairments. PCH1 is distinctly characterized by the combination with degeneration of spinal motor neurons. Recently, mutations in the exosome component 3 gene (EXOSC3) have been identified in approximately half of the patients with PCH subtype 1.
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| 13. |
- Hansson, B, et al.
(författare)
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Skeletal muscle signaling responses to resistance exercise of the elbow extensors are not compromised by a preceding bout of aerobic exercise
- 2019
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Ingår i: American journal of physiology. Regulatory, integrative and comparative physiology. - : American Physiological Society. - 1522-1490 .- 0363-6119. ; 317:1, s. R83-R92
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Tidskriftsartikel (refereegranskat)abstract
- The current study examined the effects of a preceding bout of aerobic exercise (AE) on subsequent molecular signaling to resistance exercise (RE) of the elbow extensors. Eleven men performed unilateral elbow-extensor AE (~45 min at 70% peak workload) followed by unilateral RE (4 × 7 maximal repetitions) for both arms. Thus, one arm performed AE+RE interspersed with 15 min recovery, whereas the other arm conducted RE alone. Muscle biopsies were taken from the triceps brachii of each arm immediately before (PRE) and 15 min (POST1) and 3 h (POST2) after RE. Molecular markers involved in translation initiation, protein breakdown, mechanosignaling, and ribosome biogenesis were analyzed. Peak power during RE was reduced by 24% (±19%) when preceded by AE ( P < 0.05). Increases in PGC1a and MuRF1 expression were greater from PRE to POST2 in AE+RE compared with RE (18- vs. 3.5- and 4- vs. 2-fold, respectively, interaction, P < 0.05). Myostatin mRNA decreased in both arms ( P < 0.05). Phosphorylation of AMPK (Thr172) increased (2.5-fold), and 4E-BP1 (Thr37/46) decreased (2.0-fold), after AE (interactions, P < 0.05). p70 S6K, yes-associated protein, and c-Jun NH2-terminal kinase phosphorylation were unaltered, whereas focal adhesion kinase decreased ~1.5-fold, and β1-integrin increased ~1.3- to 1.5-fold, (time effect, P < 0.05). Abundance of 45S pre-ribosomal (r)RNA (internally transcribed spacer, ITS) decreased (~30%) after AE (interaction, P < 0.05), whereas CMYC mRNA was greater in AE+RE compared with RE (12-fold, P < 0.05). POLR1B abundance increased after both AE+RE and RE. All together, our results suggest that a single bout of AE leads to an immediate decrease in signaling for translation initiation and ribosome biogenesis. Yet, this did not translate into altered RE-induced signaling during the 3-h postexercise recovery period.
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| 14. |
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| 15. |
- Jones, Owen R., et al.
(författare)
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Senescence rates are determined by ranking on the fast-slow life-history continuum
- 2008
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Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 11:7, s. 664-673
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analyses of survival senescence by using life tables have identified generalizations including the observation that mammals senesce faster than similar-sized birds. These generalizations have been challenged because of limitations of life-table approaches and the growing appreciation that senescence is more than an increasing probability of death. Without using life tables, we examine senescence rates in annual individual fitness using 20 individual-based data sets of terrestrial vertebrates with contrasting life histories and body size. We find that senescence is widespread in the wild and equally likely to occur in survival and reproduction. Additionally, mammals senesce faster than birds because they have a faster life history for a given body size. By allowing us to disentangle the effects of two major fitness components our methods allow an assessment of the robustness of the prevalent life-table approach. Focusing on one aspect of life history - survival or recruitment - can provide reliable information on overall senescence.
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| 16. |
- Jones, Robert P., et al.
(författare)
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Patterns of Recurrence After Resection of Pancreatic Ductal Adenocarcinoma : A Secondary Analysis of the ESPAC-4 Randomized Adjuvant Chemotherapy Trial
- 2019
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Ingår i: JAMA Surgery. - : AMER MEDICAL ASSOC. - 2168-6254 .- 2168-6262. ; 154:11, s. 1038-1048
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Tidskriftsartikel (refereegranskat)abstract
- Importance: The patterns of disease recurrence after resection of pancreatic ductal adenocarcinoma with adjuvant chemotherapy remain unclear.Objective: To define patterns of recurrence after adjuvant chemotherapy and the association with survival.Design, Setting, and Participants: Prospectively collected data from the phase 3 European Study Group for Pancreatic Cancer 4 adjuvant clinical trial, an international multicenter study. The study included 730 patients who had resection and adjuvant chemotherapy for pancreatic cancer. Data were analyzed between July 2017 and May 2019.Interventions: Randomization to adjuvant gemcitabine or gemcitabine plus capecitabine.Main Outcomes and Measures: Overall survival, recurrence, and sites of recurrence.Results: Of the 730 patients, median age was 65 years (range 37-81 years), 414 were men (57%), and 316 were women (43%). The median follow-up time from randomization was 43.2 months (95% CI, 39.7-45.5 months), with overall survival from time of surgery of 27.9 months (95% CI, 24.8-29.9 months) with gemcitabine and 30.2 months (95% CI, 25.8-33.5 months) with the combination (HR, 0.81; 95% CI, 0.68-0.98; P=.03). The 5-year survival estimates were 17.1% (95% CI, 11.6%-23.5%) and 28.0% (22.0%-34.3%), respectively. Recurrence occurred in 479 patients (65.6%); another 78 patients (10.7%) died without recurrence. Local recurrence occurred at a median of 11.63 months (95% CI, 10.05-12.19 months), significantly different from those with distant recurrence with a median of 9.49 months (95% CI, 8.44-10.71 months) (HR, 1.21; 95% CI, 1.01-1.45; P=.04). Following recurrence, the median survival was 9.36 months (95% CI, 8.08-10.48 months) for local recurrence and 8.94 months (95% CI, 7.82-11.17 months) with distant recurrence (HR, 0.89; 95% CI, 0.73-1.09; P=.27). The median overall survival of patients with distant-only recurrence (23.03 months; 95% CI, 19.55-25.85 months) or local with distant recurrence (23.82 months; 95% CI, 17.48-28.32 months) was not significantly different from those with only local recurrence (24.83 months; 95% CI, 22.96-27.63 months) (P=.85 and P=.35, respectively). Gemcitabine plus capecitabine had a 21% reduction of death following recurrence compared with monotherapy (HR, 0.79; 95% CI, 0.64-0.98; P=.03).Conclusions and Relevance: There were no significant differences between the time to recurrence and subsequent and overall survival between local and distant recurrence. Pancreatic cancer behaves as a systemic disease requiring effective systemic therapy after resection.Trial Registration: ClinicalTrials.gov identifier: NCT00058201, EudraCT 2007-004299-38, and ISRCTN 96397434. This secondary analysis of a randomized clinical trial investigates patterns of recurrence after adjuvant chemotherapy in pancreatic cancer and the association with survival.
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| 17. |
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| 18. |
- Nicoll, A, et al.
(författare)
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Proposed new International Health Regulations
- 2005
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Ingår i: BMJ (Clinical research ed.). - : BMJ. - 1756-1833 .- 0959-8138. ; 330:7487, s. 321-322
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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