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Future changes in interannual variability (IAV) of Arctic climate indicators such as sea ice and precipitation are still fairly uncertain. Alongside global warming-induced changes in means, a thorough understanding of IAV is needed to more accurately predict sea ice variability, distinguish trends and natural variability, as well as to reduce uncertainty around the likelihood of extreme events. In this study we rank and select CMIP6 models based on their ability to replicate observations, and quantify simulated IAV trends (1981–2100) of Arctic surface air temperature, evaporation, precipitation, and sea ice concentration under continued global warming. We argue that calculating IAV on grid points before area-averaging allows for a more realistic picture of Arctic-wide changes. Large model ensembles suggest that on shorter time scales (30 years), IAV of all variables is strongly dominated by natural variability (e.g. 93% for sea ice area in March). Long-term trends of IAV are more robust, and reveal strong seasonal and regional differences in their magnitude or even sign. For example, IAV of surface temperature increases in the Central Arctic, but decreases in lower latitudes. Arctic precipitation variability increases more in summer than in winter; especially over land, where in the future it will dominantly fall as rain. Our results emphasize the need to address such seasonal and regional differences when portraying future trends of Arctic climate variability.

Background: The primary aim was to assess the diagnostic accuracy of routine ultrasound assessment for gallbladder polyps. The secondary aim was to identify the characteristics that differentiate neoplastic polyps from nonneoplastic polyps. Methods: A total of 156 patients with histopathologically proven gallbladder polyps in 4 Dutch hospitals between 2003 and 2013 were included. Sensitivity and specificity of ultrasound for polyp size, number of polyps, and polyp type were assessed using histopathological findings as a reference standard. In addition, diagnostic accuracy of sonographic size ≥1 cm for neoplasia was assessed. Subgroup analysis for patients with polyps as primary indication for cholecystectomy was performed. The sonographic polyp characteristics on preoperative routine ultrasound were described. Results: Fifty-six percent of gallbladder polyps were preoperatively identified on ultrasound, of which 31% were neoplastic. Sensitivity and specificity of ultrasound to estimate polyp size were 93 and 43% (subgroup; 92 and 33%). Sensitivity and specificity of sonographic polyp size ≥1 cm for neoplasia were 86 and 32% (subgroup; 94 and 26%). No specific sonographic characteristics for neoplastic polyps could be established due to lack of reporting. Conclusion: Routine ultrasound assessment of polyps is associated with overestimation of polyp size and low specificity of sonographic size ≥1 cm for neoplasia, which contributes to surgical overtreatment of nonneoplastic polyps.

We developed a thyroid testing panel to assess endocrine disrupting chemicals (EDCs) capacities to bind either the thyroid receptor β (TRβ) or the thyroid hormones transporter transthyretin (TTR). We first stably transfected a human U2OS cell line with TRβ and a luciferase reporter construct to develop the TRβ CALUX® reporter gene assay to assess chemicals’ potential to interact with TRβ. Secondly, we combined a TTR-binding assay with the TRβ CALUX (TTR-TRβ CALUX) and optimized the system to evaluate the competitive properties of EDCs towards T4 for TTR binding. Both systems were evaluated with a range of known thyroid-disrupting compounds. The agonistic/antagonistic TRβ CALUX successfully predicted 9/9 and 9/12 test compounds, respectively. The TTR-TRβ CALUX predicted 9/9 compounds and demonstrated competitive activities when analyzing waste water samples. We concluded that the proposed test battery is a promising screening method able to efficiently generate data on thyroid hormone interferences by chemicals.

Antarctic mass loss is the largest contributor to uncertainties in sea level projections on centennial timescales. In this study the contribution of Antarctica’s ice discharge to future sea level changes is computed with ocean thermal forcing from 14 earth system models and linear response functions from 16 ice sheet models for three greenhouse gas emission scenarios. Different than in previous studies, basal melt was calibrated on observed Antarctic ice discharge rather than on basal melt itself with an iterative approach. For each model combination, a linear and quadratic melt dependency were calibrated both regionally (in five Antarctic sectors) and at the continental scale. Projections using all model combinations show that the variation in basal melt computation methods affect the projected sea level more than the scenario variations (SSP1-2.6 to SSP5-8.5). After calibration, a high number of model pairs still underestimated ice discharge in hindcasts over 1979–2017. Therefore top 10 % best-performing model combinations were selected for each method. A comparison between these model selections shows that the quadratic melt parameterisation with Antarctic-wide calibration performs best in reproducing past ice discharge. We conclude that calibration of basal melt on past ice discharge combined with model selection makes projections of Antarctic ice discharge (more) consistent with observations over the past four decades. Moreover, calibration of basal melt on past ice discharge results in lower basal melt sensitivities and thus lower projections of Antarctica’s sea level contribution than estimates of previous multi-model studies.

Primary high-risk human papillomavirus (hrHPV) DNA testing has been introduced in several countries worldwide, including The Netherlands. The objective of this study was to compare three automated workflow procedures for hrHPV testing of which the hrHPV detection assays meet the international guidelines for HPV testing. To mimic a realistic screening situation, we aimed to process 15 000 residual PreservCyt cervical samples in a period of 3 months. During a 3 months period, four technicians were involved in processing 5000 specimens per month on three automated platforms, (1) Qiagen Digene HC2 HPV DNA test (HC2, signal amplification); (2) Roche Cobas HPV test (DNA amplification), and (3) Hologic Aptima HPV test (RNA amplification). We measured and scored general aspects (time-to-results, hands-on-time (HOT)), maintenance, pre-run, run and post-run aspects, inventory (orders, storage), and number of errors on a scale from 1 to 10. As determined for one complete workflow each, maximum processing capacity and HOT were 296 samples and 2 h:55 m, 282 samples and 3 h:20 m, and 264 samples and 4 h:15 m for Aptima, Cobas, and HC2, respectively. The mean throughput time per run was 5 h:51 m for Cobas in which 94 samples could be processed. For Aptima, the mean throughput time per run was 6 h:30 m for 60 samples. Mean throughput time for HC2 is longer since results were provided on day 2. In this study, the fully automated Aptima workflow scores best with a 7.2, followed by Cobas with a score of 7.1 and HC2 with a score of 5.8. Although all HPV tests used in this comparison meet the international test guidelines, the performance (workflow) characteristics of the assays vary widely. A specific choice of a laboratory for high-throughput testing can be different based on the laboratory’s demands, but also hands-on-time, time-to-results/ # samples, maintenance, pre-run, run and post-run parameters, consumables, technical support, and number of errors are important operational factors for the selection of a fully automated workflow for hrHPV testing.

Long-term climate variations have the potential to amplify or dampen (human-induced) trends in temperature. Understanding natural climate variability is therefore of vital importance, especially since the variability itself may change with a changing climate. Here, we quantify the magnitude and other characteristics of interannual to decadal variability in Arctic temperature and their dependence on the climate state. Moreover, we identify the processes responsible for the state dependency of the variations, using five quasi-equilibrium climate simulations of a state-of-the-art global climate model with 0.25, 0.5, 1, 2, and 4 times present-day atmospheric CO2 forcing. The natural fluctuations in Arctic temperature, including their dependence on the state of the climate, are linked to anomalous atmospheric and oceanic heat transports toward the Arctic. Model results suggest that atmospheric heat transport leads (and also controls) Arctic temperature variations on interannual time scales, whereas oceanic transport is found to govern the fluctuations on decadal time scales. This time-scale transition of atmospheric to oceanic dominance for Arctic temperature variations is most obvious when there is interannual to decadal variability in Arctic sea ice cover. In warm climates (without Arctic sea ice cover), there is no correlation between oceanic transport and surface air temperature on any time scale. In cold climates (with full Arctic sea ice cover), interaction between ocean and atmosphere is limited, leaving poleward atmospheric heat transport to be the primary driver on all time scales (interannual and decadal).

Simulation of past climate is an important tool for the validation of climate models. The comparison with observed daily values allows us to assess the reliability of their projections on climatic extremes in a future climate. The frequency and amplitude of extreme events are fundamental aspects that climate simulations need to reproduce as they have high impacts on economy and society. The ability to simulate them will help policy makers in taking better measures to face climate change. This work aims at evaluating how six models within the High Resolution Model Intercomparison Project reproduce the trends on extreme indices as they have been observed over Europe in the 1970–2014 period. Observed values are provided by the new homogenized version of the E-OBS gridded dataset. The comparison is performed through the use of indices based on seasonal averages and on exceedances of percentile-based thresholds, focusing on six subregions. Winter-average minimum temperature is generally underestimated by models (down to − 4 °C difference over Italy and Norway) while simulated trends in seasonal averages and extreme values are found to be too cold on Eastern Europe and too warm on Iberia and Southern Europe (e.g. up to a difference of − 4% per decade on the number of Cold Nights over Spain). On the other hand the models tend to overestimate summer maximum temperatures averages in the Mediterranean Area (up to + 5 °C over the Balkans) and underestimate these at higher latitudes. Iberia, Southern and Eastern Europe are simulated with too low trends in average summer temperatures. The simulated trends are too strong on the North West part and too weak on the South East part of Europe (down to − 3%/decade on the number of Warm Days over Italy and Western Balkans). These results corroborate the findings of previous studies about the underestimation of the warming trends of summer temperatures in Southern Europe, where these are more intense and have more impacts. The high-resolution versions of the models are compared to their lower-resolution counterparts, similar to those used in the CMIP5, showing a slight improvement for the simulation of extreme winter minimum temperatures, while no significant progresses have been found for extreme summer maximum temperatures.

International audience; Winter to summer CO2 dynamics within landfast sea ice in McMurdo Sound (Antarctica) were investigated using bulk ice pCO2 measurements, air‐snow‐ice CO2 fluxes, dissolved inorganic carbon (DIC), total alkalinity (TA), and ikaite saturation state. Our results suggest depth‐dependent biotic and abiotic controls that led us to discriminate the ice column in three layers. At the surface, winter pCO2 supersaturation drove CO2 release to the atmosphere while spring‐summer pCO2 undersaturation led to CO2 uptake most of the time. CO2 fluxes showed a diel pattern superimposed upon this seasonal pattern which was potentially assigned to either ice skin freeze‐thaw cycles or diel changes in net community production. In the ice interior, the pCO2 decrease across the season was driven by physical processes, mainly independent of the autotrophic and heterotrophic phases. Bottom sea ice was characterized by a massive biomass build‐up counterintuitively associated with transient heterotrophic activity and nitrate plus nitrite accumulation. This inconsistency is likely related to the formation of a biofilm. This biofilm hosts both autotrophic and heterotrophic activities at the bottom of the ice during spring and may promote calcium carbonate precipitation.

Droughts can be studied from an atmospheric perspective by analysing the large-scale circulation resulting in a lack of water, or from a hydrological perspective by understanding the interaction of precipitation, evaporation, soil moisture and temperature at the land surface. Here, both perspectives are captured as we study the evaporative sources resulting in precipitation over the Rhine basin. These evaporative sources, being continental or oceanic, can give an indication of the vulnerability of a basin to ongoing and future land-use changes. We focus on the anomalous evaporative sources of the Rhine basin during the dry summers of 2018 and 2003, to understand what the contribution is of local recycling of precipitation versus advection of moisture into the basin to the total amount of precipitation over the Rhine basin. We do so by using ERA5 re-analysis data from 1979 to 2018 and the Eulerian moisture tracking model WAM-2layers.During an average summer, the evaporative sources of the Rhine basin are mostly located over the Atlantic ocean. In addition there is a substantial contribution of continental evaporation, mostly from land regions west of the Rhine basin. During the summer of 2018 a persistent high pressure system (blocking) prevented moisture input from the Atlantic ocean and therefore relative more recycling of moisture over land took place (both continental areas outside the basin and within the Rhine basin). Due to the anti-cyclonic movement around the high pressure area, we also found a larger contribution of evaporative sources from continental regions east of the Rhine basin.The amount of local recycling can be expressed in the precipitation recycling ratio, the local generated precipitation divided by the total precipitation in a region. We found higher than average recycling ratios during the dry summer months of 2018. Thus, due to the blocking more local evaporation resulted in precipitation over the Rhine basin, indicating the increased dependence on local land-surface processes. In general, we found a clear correlation between higher than normal recycling ratios and lower than normal precipitation in summer. An exception is the end of the dry summer of 2003, when low recycling ratios are found, probably indicating drying out of the soils and therefore lower evaporation rates.To conclude, although the summer of 2003 and 2018 were both very dry, their characteristics in terms of moisture sources and thereby their dependence on the land surface were found to be rather different. In 2018, local recycling was important, contrasting to 2003 when the drying out of the soils made local recycling less important. These differences between two dry years over the same region highlight the important role of the land surface in precipitation feedbacks.

Enhanced ocean heat transport into the Arctic is linked to stronger future Arctic warming and polar amplification. To quantify the impact of ocean heat transport on Arctic climate, it is imperative to understand how its magnitude and the associated mechanisms change in other climate states. This paper therefore assesses the ocean heat transport into the Arctic at $$70^{\circ }\hbox {N}$$ for climates forced with a broad range of carbon dioxide concentration levels, ranging from one-fourth to four times modern values. We focused on ocean heat transports through the Arctic entrances (Bering Strait, Canadian Archipelago, and Nordic Seas) and identified relative contributions of volume and temperature to these changes. The results show that ocean heat transport differences across the five climate states are dominated by heat transport changes in the Nordic Seas, although in the warmest climate state heat transport through the Bering Strait plays an almost equally important role. This is primarily caused by changes in horizontal currents owing to anomalous wind responses and to differential advection of thermal anomalies. Changes in sea ice cover play a prominent role by modulating the surface heat fluxes and the impact of wind stresses on ocean currents. The Atlantic meridional overturning circulation and its associated heat transport play a more modest role in the ocean heat transport into the Arctic. The net effect of these changes is that the poleward ocean heat transport at $$70^{\circ }\hbox {N}$$ strongly increases from the coldest climate to the warmest climate state.

Background To overcome the limitations regarding two dimensional (2D) greyscale (GS) transrectal ultrasound (TRUS)-guided biopsy in prostate cancer (PCa) detection and tissue packaging in biopsy processing, there is an ongoing focus on new imaging and pathology techniques. A three-dimensional (3D) model of the prostate with biopsy needle guidance can be generate by the Navigo™ workstation (UC-care, Israel). The SmartBX™ system (UC-care, Israel) provides a prostate biopsy core preembedding method. The aim of this study was to compare cancer detection rates between the 3D TRUS-guidance and preembedding method with conventional 2D GS TRUS-guidance among patients undergoing prostate biopsies. Methods We retrospectively analyzed the records of all patients who underwent prostate biopsies for PCa detection at our institution from 2007 to 2016. The cohort was divided into a 2D GS TRUS-guidance cohort (from 2007 to 2013, n = 1149) and a 3D GS TRUS-guidance with preembedding cohort (from 2013 to 2016, n = 469). Effect of 3D GS TRUS-guidance with preembedding on detection rate of PCa and clinically significant PCa (Gleason score ≥ 7 or > 2 biopsy cores with a Gleason score 6) was compared to 2D GS TRUS-guidance using regression models. Results Detection rate of PCa and clinically significant PCa was 39.0 and 24.9% in the 3D GS TRUS cohort compared to 33.5 and 19.0% in the 2D GS TRUS cohort, respectively. On multivariate regression analysis the use of 3D GS TRUS-guidance with preembedding was associated with a significant increase in detection rate of PCa (aOR = 1.33; 95% CI: 1.03–1.72) and clinically significant PCa (aOR = 1.47; 95% CI: 1.09–1.98). Conclusion Our results suggest that 3D GS TRUS-guidance with biopsy core preembedding improves PCa and clinically significant PCa detection compared to 2D GS TRUS-guidance. Additional studies are needed to justify the application of these systems in clinical practice. Electronic supplementary material The online version of this article (10.1186/s12894-019-0455-7) contains supplementary material, which is available to authorized users.

Global climate models project an intensification of future soil moisture droughts over large parts of Europe. This paper investigates the impact of model resolution on the severity and seasonal cycle of future European droughts. We use a 6-member ensemble of the general circulation model EC-Earth to study two periods representative of the start and end of the 21st century under low-to-moderate greenhouse gas forcing (RCP4.5). In our study area, central-western Europe, at high spatial resolution (~ 25 km) droughts are more severe and start earlier in the season than at standard resolution (~ 112 km). Here, changes in the large-scale atmospheric circulation and local soil moisture feedbacks lead to enhanced evapotranspiration in spring and reduced precipitation in summer. A more realistic position of the storm track at high model resolution leads to reduced biases in precipitation and temperature in the present-day climatology, which act to amplify evapotranspiration in spring. Furthermore, in the high resolution model a stronger anticyclonic anomaly over the British Isles extends over our study region and supports soil drying. The resulting drier soil induces stronger soil moisture feedbacks that amplify drought conditions in summer. In addition, soil moisture-limited evapotranspiration in summer promotes sensible heating of the boundary layer, which leads to a lower relative humidity with less cloudy conditions, an increase of dry summer days, and more incoming solar radiation. As a result a series of consecutive hot and dry summers appears in the future climate. The enhanced drying at high spatial resolution suggests that future projections of central-western European droughts by CMIP5 models have been potentially underestimated.

It is currently unknown how cigarette smoke-induced airway remodelling affects highly expressed respiratory epithelial defence proteins and thereby mucosal host defence.Localisation of a selected set of highly expressed respiratory epithelial host defence proteins was assessed in well-differentiated primary bronchial epithelial cell (PBEC) cultures. Next, PBEC were cultured at the air–liquid interface, and during differentiation for 2–3 weeks exposed daily to whole cigarette smoke. Gene expression, protein levels and epithelial cell markers were subsequently assessed. In addition, functional activities and persistence of the cigarette smoke-induced effects upon cessation were determined.Expression of the polymeric immunoglobulin receptor, secretory leukocyte protease inhibitor and long and short PLUNC (palate, lung and nasal epithelium clone protein) was restricted to luminal cells and exposure of differentiating PBECs to cigarette smoke resulted in a selective reduction of the expression of these luminal cell-restricted respiratory host defence proteins compared to controls. This reduced expression was a consequence of cigarette smoke-impaired end-stage differentiation of epithelial cells, and accompanied by a significant decreased transepithelial transport of IgA and bacterial killing.These findings shed new light on the importance of airway epithelial cell differentiation in respiratory host defence and could provide an additional explanation for the increased susceptibility of smokers and patients with chronic obstructive pulmonary disease to respiratory infections.

The predominant decadal to multidecadal variability in the Arctic region is a feature that is not yet well-understood. It is shown that the Barents Sea is a key region for Arctic-wide variability. This is an important topic because low-frequency changes in the ocean might lead to large variations in the sea-ice cover, which then cause massive changes in the ocean-atmosphere heat exchanges. Here we describe the mechanism driving surface temperatures and heat fluxes in the Barents Sea based primarily on analyzes of one global coupled climate model. It is found that the ocean drives the low-frequency changes in surface temperature, whereas the atmosphere compensates the oceanic transport anomalies. The seasonal dependence and the role of individual components of the ocean-atmosphere energy budget are analyzed in detail, showing that seasonally-varying climate mechanisms play an important role. Herein, sea ice is governing the seasonal response, by acting as a lid that opens and closes during warm and cold periods, respectively, thereby modulating the surface heat fluxes.

Objective: Three patients with intractable Tourette syndrome (TS) underwent thalamic deep brain stimulation (DBS). To investigate the role of thalamic electrical activity in tic generation, local field potentials (LFP), EEG and EMG simultaneously were recorded.Methods: Event related potentials and event related spectral perturbations of EEG and LFP, event related cross-coherences between EEG/LFP and LFP/LFP were analyzed. As time locking events, the tic onsets were used. Spontaneous tics were compared to voluntary tic mimicking. The effect of tic suppression and DBS on thalamic LFPs was evaluated.Results: All three patients showed time-locked and prior to onset of spontaneous motor tics thalamic synchronization and thalamo-cortical cross-coherence. Also in three patients, not time-locked to motor tics, increased intra-thalamic coherences in the 1-8 Hz frequency band were found. In one patient it was demonstrated that voluntary mimicked tics were preceded by premotor cortical and thalamic potentials. In this patient unilateral thalamic DBS contralaterally decreased the background thalamic activity.Conclusions: The present study in three cases with TS shows that spontaneous tics in TS are preceded by repetitive coherent thalamo-cortical discharges, indicating that preceding a tic the basal ganglia circuits are "charged up", ultimately leading to a motor tic.Significance: Thalamic LFP recording may lead to more insight in underlying pathophysiological mechanisms in TS. (c) 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

The correction of most cases of skeletal class II mandibular deficiency requires surgical advancement of the mandible for treatment of the malocclusion. Often genioplasty is included in the procedure to improve the soft tissue profile. Long-term skeletal stability is an important goal for the surgeon and orthodontist following bilateral sagittal split osteotomy (BSSO) and is influenced by the muscles attached to the mandible. Following the surgical advancement of the mandible, the suprahyoid muscle complex is stretched and even more so when the procedure is combined with surgical advancement of the chin. This retrospective comparative study determined the long-term skeletal stability of patients who had undergone surgical advancement of the mandible by means of BSSO with an advancement genioplasty, compared to those who had undergone mandibular advancement surgery (BSSO) without an advancement genioplasty. This study concluded that the postoperative hard tissue relapse following BSSO advancement, with or without genioplasty, was clinically insignificant.

Cigarette smoking (CS) is known to increase susceptibility to respiratory tract infections and alter differentiation of airway epithelial cells. Host defence proteins (HDPs) are key mediators of mucosal host defence. We hypothesized that CS-induced alterations in epithelial differentiation result in a decrease in constitutively expressed HDPs, thus rendering the host more susceptible to infection. Primary bronchial epithelial cells (PBEC) were cultured at the air-liquid interface (ALI) and during differentiation daily exposed to whole CS. Gene expression and protein levels of HDPs and epithelial cell-specific markers were subsequently assessed, and host defence activities were tested. CS-exposure of differentiating PBEC up to 19 days resulted in impaired epithelial differentiation and a reduction in luminal cell-specific HDP expression (i.e. SLPI, pIgR and short/long PLUNC) compared to controls. This was partly restored upon cessation of CS exposure. This reduced expression was accompanied by a significantly decreased trans-epithelial transport of dimeric IgA (~75% reduction) and a reduced killing of M. catarrhalis. Whether and how these changes affect airway microbiome composition is currently under investigation. These findings shed new light on the importance of airway epithelial cell differentiation in respiratory host defence and could provide an additional explanation for the increased susceptibility of smokers and COPD patients to respiratory infections. This work was supported by a Marie Curie Intra-European Fellowship (#622815), the Lung Foundation Netherlands (#5.1.13.033), Eurostars NAS-AMP (#E!9795) and a research grant from Galapagos N.V.

Background Not all patients where an ambulance is dispatched are conveyed to an emergency department. Although non-conveyance is a substantial part of ambulance care, there is limited insight in the non-conveyance patient population. Therefore, the study aim was to compare demographics, initial on-scene reasons for care, and vital signs between conveyed and non-conveyed patients attended by an ambulance. Methods A retrospective study of ambulance runs from 2 EMS regions in the Netherlands in 2016 was performed. For each ambulance run demographics (age, gender and geographical location), initial reasons for care categorised into the ICD-10 classification system, and vital functions or observational scales (according to the national ambulance care protocol) were collected and analyzed. Results 54.797 ambulance runs met the inclusion criteria, of which 14.383/54.797 (26.2%) resulted in non-conveyance. There was no significant difference in gender, but the non-conveyance group was significantly younger (48.5 (±26.4) years) compared to the conveyance group (60.7 (±22.2) years) (p = .000). The most common initial reasons for care for the conveyance group could be classified into chapter-9 diseases of the circulatory system, chapter-19 injury, poisoning and certain other consequences of external causes, and chapter-10 diseases of the respiratory system. The most common reasons for care in the non-conveyance group could be classified into the chapter-9 diseases of the circulatory system, chapter-19 injury, poisoning and certain other consequences of external causes, and -chapter-5 mental, behavioral and neurodevelopmental disorders. The total percentage abnormal vital functions/observation scales between the conveyance (69.5%) and non-conveyance group (58.6%) was significantly different (p = .000). 15 out of 17 vital functions/observation scales are significantly different between the conveyance and non-conveyance group. Conclusions This study shows that non-conveyed patients are younger, are more likely to be in (highly) rural areas, and more often have initial reasons for care related to mental, behavioral and neurodevelopmental disorders (ICD-10 chapter 5). Although abnormal vital functions/observation scale were more prevalent in the conveyance group, 58.6% of the non-conveyed patients had at least one abnormal vital function/observation scale.

The combination of in vitro bioassays and chemical screening can provide a powerful toolbox to determine biologically relevant compounds in water extracts. In this study, a sample preparation method is evaluated for the suitability for both chemical analysis and in vitro bioassays. A set of 39 chemicals were spiked to surface water, which were extracted using Oasis MCX cartridges. The extracts were chemically analyzed by liquid chromatography linear ion trap Orbitrap analysis and recoveries appeared to be on average 61% Compounds with log Kow values in the range between 0 and 4 are recovered well using this method. In a next step, the same extracts were tested for genotoxic activity using the Comet assay and Ames fluctuation test and for specific endocrine receptor activation using a panel of CALUX assays, for estrogenic (ER), androgenic (AR), glucocorticoid (GR), progestagenic (PR), and thyroidogenic (TR) agonistic activities. The results of the genotoxicity assays indicated that spiked genotoxic compounds were preserved during sample preparation. The measured responses of the GR CALUX and ER CALUX assays were similar to the predicted responses. The measured responses in the AR CALUX and PR CALUX assays were much lower than expected from the analytical concentration, probably due to antagonistic effects of some spiked compounds. Overall, the presented sample preparation method seems to be suitable for both chemical analysis and specific in vitro bioassay applications.

Natural decadal variability of surface air temperature might obscure Arctic temperature trends induced by anthropogenic forcing. It is therefore imperative to know how Arctic decadal variability (ADV) will change as the climate warms. In this study, we evaluate ADV characteristics in three equilibrium climates with present-day, double, and quadrupled atmospheric CO2 forcing. The dominant region of variability, which is located over the Barents and Greenland Sea at present, shifts to the central Arctic and Siberian regions as the climate warms. The maximum variability in sea ice cover and surface air temperature occurs in the CO2 doubling climate when sea ice becomes more vulnerable to melt over vast stretches of the Arctic. Furthermore, the links between dominant atmospheric circulation modes and Arctic surface climate characteristics vary strongly with climate change. For instance, a positive Arctic Oscillation index is associated with a colder Arctic in warmer climates, instead of a warmer Arctic at present. Such changing relationships are partly related to the retreat of sea ice because altered wind patterns influence the sea ice distribution and hence the associated local surface fluxes. The atmospheric pressure distributions governing ADV and the associated large-scale dynamics also change with climate warming. The changing character of the ADV shows that it is vital to consider (changes in) ADV when addressing Arctic warming in climate model projections.

BACKGROUND: Chemoradiotherapy (CRT) is a major risk factor for malnutrition and dehydration in patients with head and neck cancer. Enteral support is often needed, and a percutaneous endoscopic gastrostomy (PEG) is frequently placed. Specific indicators for PEG placement remain unclear. This study retrospectively determined which factors contributed to enteral nutrition (EN) use and PEG placement in a large patient group to gain insight on potential indicators for PEG placement protocol creation. METHODS: A retrospective chart review of 240 patients with head and neck cancer who underwent CRT in 2012-2015 was conducted. Lifestyle, oncological, treatment, and nutrition outcome characteristics were examined and compared between patients who used EN and those who did not, as well as between patients who received a PEG and those who did not. RESULTS: In total, 195 patients used EN (via PEG or nasogastric tube). Multivariate analysis showed that nodal disease presence ( P = .01) and bilateral neck irradiation ( P = .01) were significantly related to EN use while increased age ( P = .01), nodal disease presence ( P = .02), reconstruction extent other than primary closure ( P = .02), bilateral neck irradiation ( P < .01), and an adapted intake consistency prior to treatment ( P = .03) were significantly related to PEG placement. CONCLUSION: Important factors for EN usage and PEG placement consideration include nodal disease and planned bilateral neck irradiation. Results from this study in combination with existing literature can be taken into consideration in the design of a PEG placement protocol. A better understanding of predictive indicators to PEG placement should be explored in further prospective studies.

Occult nodal tumour cells should be categorised as micrometastasis (MMs) and isolated tumour cells (ITCs). A recent meta-analysis demonstrated that MMs, but not ITCs, are prognostic for disease recurrence in patients with stage I/II colon cancer.The objective of this retrospective multicenter study was to correlate MMs and ITCs to characteristics of the primary tumour, and to determine their prognostic value in patients with stage I/II colon cancer.One hundred ninety two patients were included in the study with a median follow up of 46 month (IQR 33-81 months). MMs were found in eight patients (4.2%), ITCs in 37 (19.3%) and occult tumour cells were absent in 147 patients (76.6%). Between these groups, tumour differentiation and venous or lymphatic invasion was equally distributed. Advanced stage (pT3/pT4) was found in 66.0% of patients without occult tumour cells (97/147), 72.9% of patients with ITCs (27/37), and 100% in patients with MMs (8/8), although this was a non-significant trend. Patients with MMs showed a significantly reduced 3 year-disease free survival compared to patients with ITCs or patients without occult tumour cells (75.0% versus 88.0% and 94.8%, respectively, p = 0.005). When adjusted for T-stage, MMs independently predicted recurrence of cancer (OR 7.6 95% CI 1.5-37.4, p = 0.012).In this study, the incidence of MMs and ITCs in patients with stage I/II colon cancer was 4.2% and 19.3%, respectively. MMs were associated with an reduced 3 year disease free survival rate, but ITCs were not.

Respiratory infections are a major health burden in smokers, and contribute to exacerbations, development and progression of chronic obstructive pulmonary disease (COPD). The mechanisms underlying the increased susceptibility of smokers with or without COPD to these infections can be attributed in part to disrupted mucociliary clearance by the airway epithelium. Currently it is incompletely understood how cigarette smoke (CS) affects production of constitutively expressed AMPs, an important contributor to epithelial antimicrobial barrier function. We hypothesized that CS-induced alterations in epithelial differentiation result in a decrease in constitutively expressed AMPs, thus rendering the host more susceptible to infection. To investigate this, primary bronchial epithelial cells (PBEC;n=7) were cultured at the air-liquid interface and daily exposed to CS for 2-3 weeks. Markers of basal and luminal epithelial cells and AMPs were assessed by qPCR, ELISA and immunofluorescence. Results showed that PBEC differentiation into luminal cells was significantly (p Supported by a Marie Curie Intra-European Fellowship (#622815), Galapagos N.V and the Lung Foundation Netherlands (grant # 5.1.13.033).

This paper describes the complete findings of the EU-funded research project OPTIMISC, which investigated methods to optimize the production and use of miscanthus biomass. Miscanthus bioenergy and bioproduct chains were investigated by trialing 15 diverse germplasm types in a range of climatic and soil environments across central Europe, Ukraine, Russia, and China. The abiotic stress tolerances of a wider panel of 100 germplasm types to drought, salinity, and low temperatures were measured in the laboratory and a field trial in Belgium. A small selection of germplasm types was evaluated for performance in grasslands on marginal sites in Germany and the UK. The growth traits underlying biomass yield and quality were measured to improve regional estimates of feedstock availability. Several potential high-value bioproducts were identified. The combined results provide recommendations to policymakers, growers and industry. The major technical advances in miscanthus production achieved by OPTIMISC include: (1) demonstration that novel hybrids can out-yield the standard commercially grown genotype Miscanthus x giganteus; (2) characterization of the interactions of physiological growth responses with environmental variation within and between sites; (3) quantification of biomass-quality-relevant traits; (4) abiotic stress tolerances of miscanthus genotypes; (5) selections suitable for production on marginal land; (6) field establishment methods for seeds using plugs; (7) evaluation of harvesting methods; and (8) quantification of energy used in densification (pellet) technologies with a range of hybrids with differences in stem wall properties. End-user needs were addressed by demonstrating the potential of optimizing miscanthus biomass composition for the production of ethanol and biogas as well as for combustion. The costs and life-cycle assessment of seven miscanthusbased value chains, including small- and large-scale heat and power, ethanol, biogas, and insulation material production, revealed GHG-emission- and fossil-energy-saving potentials of up to 30.6 t CO2eqC ha(-1) y(-1) and 429 GJ ha(-1)y(-1), respectively. Transport distance was identified as an important cost factor. Negative carbon mitigation costs of-78 epsilon t(-1) CO2eq C were recorded for local biomass use. The OPTIMISC results demonstrate the potential of miscanthus as a crop for marginal sites and provide information and technologies for the commercial implementation of miscanthus-based value chains.

Purpose Pulsed electromagnetic fields (PEMF) are currently used in the treatment of spinal fusions and non-unions. There are indications that PEMF might also be effective in the treatment of osteoporosis. In this study we examined whether whole-body PEMF treatment affects the bone microarchitecture in an osteoporotic rat model. Methods Twenty-week-old female rats were ovariectomised (n = 20). Four different PEMF treatment protocols based on previous experimental studies and based on clinically used PEMF signals were examined (2 h/day, 5 days/week). A control group did not receive PEMF. At zero, three and six weeks cancellous and cortical bone architectural changes at the proximal tibia were evaluated using in vivo microCT scanning. Results PEMF treatment did not induce any changes in cancellous or cortical bone compared to untreated controls. Conclusions Although previous studies have shown strong effects of PEMF in osteoporosis we were unable to demonstrate this in any of the treatment protocols. Using in vivo microCT scanning we were able to identify small bone changes in time. Subtle differences in the experimental set-up might explain the differences in study outcomes in the literature. Since PEMF treatment is safe, future experimental studies on the effect of PEMF on bone can better be performed directly on humans, eliminating the potential translation issues between animals and humans. In this study we found no support for the use of PEMF in the treatment of osteoporosis.

Item does not contain fulltext BACKGROUND: Tension-band wiring (TBW) has been accepted as the treatment of choice for displaced olecranon fractures. The aim of this study was to examine the effect of K-wire position on instability of the K-wires in relation to local complications and radiological and clinical long-term outcome. METHODS: We reviewed the early follow-up of 59 patients (mean age, 60 years) who underwent TBW osteosynthesis for displaced olecranon fractures. Follow-up information was available from medical records and radiographs. The main outcome measurements were proximal migration of the wires, gap, step, range of motion, and complications. Long-term follow-up included 21 patients (mean age, 58 years). Follow-up was available from a clinical visit and a radiograph. Visual Analogue Scale (VAS), Mayo Elbow Performance Score (MEPS), Disabilities of the Arm Shoulder and Hand (DASH), EuroQol-5D (EQ-5D), and Broberg and Morrey osteoarthritis scores were obtained. RESULTS: Seventy-eight percent of the patients treated with intramedullary K-wires were found to have instability of K-wires, compared to 36% in the patients treated with transcortical K-wires. Patients with instability of the K-wires tend to develop osteoarthritis more often. There is a better functional outcome in patients where the osteosynthetic material is removed. CONCLUSION: Instability of K-wires after TBW is more common after intramedullary placement of the wires resulting in proximal migration of the K-wires and gap appearance. There was a tendency of more osteoarthritis in the group of patients where instability of K-wires was identified. We would recommend the use of transcortical placed wires, as well as to have a low threshold in removing the implants. 01 maart 2012

Amplified Arctic warming is one of the key features of climate change. It is evident in observations as well as in climate model simulations. Usually referred to as Arctic amplification, it is generally recognized that the surface albedo feedback governs the response. However, a number of feedback mechanisms play a role in AA, of which those related to the prevalent near-surface inversion have received relatively little attention. Here we investigate the role of the near-surface thermal inversion, which is caused by radiative surface cooling in autumn and winter, on Arctic warming. We employ idealized climate change experiments using the climate model EC-Earth together with ERA-Interim reanalysis data to show that boundary-layer mixing governs the efficiency by which the surface warming signal is ‘diluted’ to higher levels. Reduced vertical mixing, as in the stably stratified inversion layer in Arctic winter, thus amplifies surface warming. Modelling results suggest that both shortwave—through the (seasonal) interaction with the sea ice feedback—and longwave feedbacks are affected by boundary-layer mixing, both in the Arctic and globally, with the effect on the shortwave feedback dominating. The amplifying effect will decrease, however, with climate warming because the surface inversion becomes progressively weaker. We estimate that the reduced Arctic inversion has slowed down global warming by about 5% over the past 2 decades, and we anticipate that it will continue to do so with ongoing Arctic warming.

We evaluated the applicability of combining in vitro bioassays with instrument analyses to identify potential endocrine disrupting pollutants in sulfuric acid-treated extracts of liver and/or blubber of high trophic-level animals. Dioxin-like and androgen receptor (AR) antagonistic activities were observed in Baikal seals, common cormorants, raccoon dogs, and finless porpoises by using a panel of rat and human cell-based chemical-activated luciferase gene expression (CALUX) reporter gene bioassays. On the other hand, no activity was detected in estrogen receptor α (ERα)-, glucocorticoid receptor (GR)-, progesterone receptor (PR)-, and peroxisome proliferator-activated receptor γ2 (PPARγ2)-CALUX assays with the sample amount applied. All individual samples (n = 66) showed dioxin-like activity, with values ranging from 21 to 5500 pg CALUX-2,3,7,8-tetrachlorodibenzo-p-dioxin equivalent (TEQ)/g-lipid. Because dioxins are expected to be strong contributors to CALUX-TEQs, the median theoretical contribution of dioxins calculated from the result of chemical analysis to the experimental CALUX-TEQs was estimated to explain up to 130% for all the tested samples (n = 54). Baikal seal extracts (n = 31), but not other extracts, induced AR antagonistic activities that were 8-150 μg CALUX-flutamide equivalent (FluEQ)/g-lipid. p,p′-DDE was identified as an important causative compound for the activity, and its median theoretical contribution to the experimental CALUX-FluEQs was 59% for the tested Baikal seal tissues (n = 25). Our results demonstrate that combining in vitro CALUX assays with instrument analysis is useful for identifying persistent organic pollutant-like compounds in the tissue of wild animals on the basis of in vitro endocrine disruption toxicity. © 2011 American Chemical Society.

From this investigation it is concluded that expansine C7H6O4, a substance with bactericidal and fungicidal properties isolated by Oosterhuis and Luyken 1 ) from the culture liquid of Penicillium expansum Westl., very probably has the structure of an anhydro-3-hydroxymethylene-tetrahydro-γ-pyron-2-carboxylic acid. Expansine is probably identical with patulin 1 ), claviformin 2 ) and clavacin 3 ).

An apparatus is described for the preparation of pure silicon by thermal decomposition of trichlorosilane on a hot tantalum wire in a hydrogen atmosphere. The polycrystalline silicon is obtained in the form of rods with a diameter of about 15 mm and a length of 20-40 cm. The yield of Si is 45-50 % if calculated on the Si-content of SiHCl3. From resistivity measurements, the boron content of the silicon obtained can be calculated to be 0.5 × 10−6% (resistivity of single crystals about 300–500 ohm-cm p-type).