84 research outputs found

    Response to commentary by J. L. Bamber, W. P. Aspinall and R. M. Cooke (2016)

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    In a commentary paper, Bamber et al. (Nat Clim Change 3:424–427, 2016) respond to our recent assessment (De Vries and Van de Wal Clim Change 1–14, 2015) of their expert judgment based study on projections of future sea level rise due to the melting of the large ice sheets (Bamber and Aspinall Nat Clim Chang 3:424–427, 2013). In this response we comment on their remarks

    Two-Step 3D-Guided Supramalleolar Osteotomy to Treat Varus Ankle osteoarthritis

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    Background: Success of valgus-type supramalleolar osteotomy (SMOT) depends on adequate correction of malalignment, which can be hard to achieve with current 2-dimensional (2D) planning and operative techniques. A personalized digital 3-dimensional (3D) workflow to virtually plan and perform a 2-step 3D-guided medial opening (MO) SMOT has the potential to improve precision of correction. Methods: Computed tomography (CT)-based Proplan medical 3D models were made to virtually plan the desired MO SMOT, and exported to 3-Matic medical to develop patient-specific 2-step cutting and wedge guides. Workflow accuracy was tested in this limited clinical pilot study (3 patients) by comparing the virtual planned position of the osteotomized distal tibial fragment with the I -year post-MO SMOT configuration. Two millimeters or less translation deviation in every plane was defined as accurate. Results: Primary outcome analysis of the osteotomized distal tibial fragment deviation showed a median translation in all planes of 0.7 (range 0-8.2) mm (interquartile range 1.55) with an excellent interrater reliability of the measurements (intraclass correlation coefficient 0.998). There was a strong reduction in ankle pain as reflected by an increase of the AOFAS-AH score and decrease of NRS pain score with an unrestricted hindfoot motion 1 year after surgery. Conclusion: 3D virtually planned bone cutting and wedge guides is a promising approach associated with minimal postoperative deviation from the desired correction in medial opening supramalleolar osteotomy

    The role of ATM and 53BP1 as predictive markers in cervical cancer

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    Treatment of advanced-stage cervical cancers with (chemo)radiation causes cytotoxicity through induction of high levels of DNA damage. Tumour cells respond to DNA damage by activation of the DNA damage response (DDR), which induces DNA repair and may counteract chemoradiation efficacy. Here, we investigated DDR components as potential therapeutic targets and verified the predictive and prognostic value of DDR activation in patients with cervical cancer treated with (chemo)radiation. In a panel of cervical cancer cell lines, inactivation of ataxia telangiectasia mutated (ATM) or its substrate p53-binding protein-1 (53BP1) clearly gave rise to cell cycle defects in response to irradiation. Concordantly, clonogenic survival analysis revealed that ATM inhibition, but not 53BP1 depletion, strongly radiosensitised cervical cancer cells. In contrast, ATM inhibition did not radiosensitise non-transformed epithelial cells or non-transformed BJ fibroblasts. Interestingly, high levels of active ATM prior to irradiation were related with increased radioresistance. To test whether active ATM in tumours prior to treatment also resulted in resistance to therapy, immunohistochemistry was performed on tumour material of patients with advanced-stage cervical cancer (n = 375) treated with (chemo)radiation. High levels of phosphorylated (p-)ATM [p = 0.006, hazard ratio (HR) = 1.817] were related to poor locoregional disease-free survival. Furthermore, high levels of p-ATM predicted shorter disease-specific survival (p = 0.038, HR = 1.418). The presence of phosphorylated 53BP1 was associated with p-ATM (p = 0.001, odds ratio = 2.206) but was not related to any clinicopathological features or survival. In conclusion, both our in vitro and patient-related findings indicate a protective role for ATM in response to (chemo)radiation in cervical cancer and point at ATM inhibition as a possible means to improve the efficacy of (chemo)radiation

    Attribution of the heavy rainfall events leading to severe flooding in Western Europe during July 2021

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    In July 2021 extreme rainfall across Western Europe caused severe flooding and substantial impacts, including over 200 fatalities and extensive infrastructure damage within Germany and the Benelux countries. After the event, a hydrological assessment and a probabilistic event attribution analysis of rainfall data were initiated and complemented by discussing the vulnerability and exposure context. The global mean surface temperature (GMST) served as a covariate in a generalised extreme value distribution fitted to observational and model data, exploiting the dependence on GMST to estimate how anthropogenic climate change affects the likelihood and severity of extreme events. Rainfall accumulations in Ahr/Erft and the Belgian Meuse catchment vastly exceeded previous observed records. In regions of that limited size the robust estimation of return values and the detection and attribution of rainfall trends are challenging. However, for the larger Western European region it was found that, under current climate conditions, on average one rainfall event of this magnitude can be expected every 400 years at any given location. Consequently, within the entire region, events of similar magnitude are expected to occur more frequently than once in 400 years. Anthropogenic climate change has already increased the intensity of the maximum 1-day rainfall event in the summer season by 3–19 %. The likelihood of such an event to occur today compared to a 1.2 ∘ C cooler climate has increased by a factor of 1.2–9. Models indicate that intensity and frequency of such events will further increase with future global warming. While attribution of small-scale events remains challenging, this study shows that there is a robust increase in the likelihood and severity of rainfall events such as the ones causing extreme impacts in July 2021 when considering a larger region

    Attribution of the heavy rainfall events leading to severe flooding in Western Europe during July 2021

    Get PDF
    In July 2021 extreme rainfall across Western Europe caused severe flooding and substantial impacts, including over 200 fatalities and extensive infrastructure damage within Germany and the Benelux countries. After the event, a hydrological assessment and a probabilistic event attribution analysis of rainfall data were initiated and complemented by discussing the vulnerability and exposure context. The global mean surface temperature (GMST) served as a covariate in a generalised extreme value distribution fitted to observational and model data, exploiting the dependence on GMST to estimate how anthropogenic climate change affects the likelihood and severity of extreme events. Rainfall accumulations in Ahr/Erft and the Belgian Meuse catchment vastly exceeded previous observed records. In regions of that limited size the robust estimation of return values and the detection and attribution of rainfall trends are challenging. However, for the larger Western European region it was found that, under current climate conditions, on average one rainfall event of this magnitude can be expected every 400 years at any given location. Consequently, within the entire region, events of similar magnitude are expected to occur more frequently than once in 400 years. Anthropogenic climate change has already increased the intensity of the maximum 1-day rainfall event in the summer season by 3–19 %. The likelihood of such an event to occur today compared to a 1.2 ∘^{\circ }C cooler climate has increased by a factor of 1.2–9. Models indicate that intensity and frequency of such events will further increase with future global warming. While attribution of small-scale events remains challenging, this study shows that there is a robust increase in the likelihood and severity of rainfall events such as the ones causing extreme impacts in July 2021 when considering a larger region
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