Complications after plate fixation and elastic stable intramedullary nailing of dislocated midshaft clavicle fractures: a retrospective comparison

PURPOSE: The incidence of operative treatment of dislocated midshaft clavicle fractures (DMCF) is rising due to unsatisfactory results after non-operative treatment. Knowledge of complications is important for selection of the surgical technique and preoperative patient counselling. The aim of this study is to compare complications after plate fixation and elastic stable intramedullary nailing (ESIN) with a titanium elastic nail (TEN) for DMCF. METHODS: A retrospective analysis of our surgical database was performed. From January 2005 to January 2010, 90 patients with DMCF were treated with plate fixation or ESIN. Complications were evaluated in both treatment groups and subsequently compared. RESULTS: Seven implant failures occurred in six patients (14 %) of the plate group and one implant failure (2.1 %) was seen in the ESIN group (p = 0.051). Major revision surgery was performed in five cases in the plate group (11.6 %) and in one case (2.1 %) in the ESIN group (p = 0.100). Three refractures (7.0 %) were observed in the plate group after removal of the implant against none in the ESIN group (p = 0.105). Six minor revisions (13 %) were reported in the ESIN group and none were reported in the plate group (p = 0.027). CONCLUSIONS: Compared to other studies we report higher rates of refracture (7.0 %), major revision surgery (11.6 %) and implant failure (14.0 %) after plate fixation. The frequency of implant failures differed almost significantly for patients treated with plate fixation compared to ESIN. Furthermore, a tendency towards refracture after implant removal and major revision surgery after plate fixation was observed

Monitoring vegetation dynamics using meris fused images

The MEdium Resolution Imaging Spectrometer (MERIS) can be used to monitor vegetation dynamics at regional to global scales. However, the spatial resolutions provided by this sensor (300 or 1200 m) might not be appropriate to monitor fragmented landscapes. This is why the synergistic use of MERIS full resolution (300 m) and a high spatial resolution land use/land cover database (25 m) is studied in this paper. An unmixing-based data fusion approach was used to produce images that have the spectral and temporal resolutions provided by MERIS and a Landsat-like spatial resolution. The central part of The Netherlands was selected to illustrate this approach. Seven MERIS full resolution and one Landsat TM image were available over this area too. The radiometric characteristics of the fused images were evaluated at 25 and at 300 m. After this quantitative quality assessment, the best fused images were used to compute MTCI and MGVI profiles for the main land cover types present in the study area

Estimating forest parameters from top of atmosphere multi-angular radiance data using coupled radiative transfer models

ABSTRACT -Traditionally, the estimation of forest parameters using physically-based canopy radiative transfer models (RT

Spatio-temporal assessment of beech growth in relation to climate extremes in Slovenia – An integrated approach using remote sensing and tree-ring data

Climate change is predicted to affect tree growth due to increased frequency and intensity of extreme events such as ice storms, droughts and heatwaves. Yet, there is still a lot of uncertainty on how trees respond to an increase in frequency of extreme events. Use of both ground-based wood increment (i.e. ring width) and remotely sensed data (i.e. vegetation indices) can be used to scale-up ground measurements, where there is a link between the two, but this has only been demonstrated in a few studies. We used tree-ring data together with crown features derived from the Moderate Resolution Imaging Spectroradiometer (MODIS) to assess the effect of extreme climate events on the growth of beech (Fagus sylvatica L.) in Slovenia. We found evidence that years with climate extremes during the growing season (drought, high temperatures) had a lower ring width index (RWI) but we could not find such evidence for the remotely sensed EVI (Enhanced Vegetation Index). However, when assessing specific events where leaf burning or wilting has been reported (e.g. August 2011) we did see large EVI anomalies. This implies that the impact of drought or heatwave events cannot be captured by EVI anomalies until physical damage on the canopy is caused. This also means that upscaling the effect of climate extremes on RWI by using EVI anomalies is not straightforward. An exception is the 2014 ice storm that caused a large decline in both RWI and EVI. Extreme climatic parameters explained just a small part of the variation in both RWI and EVI by, which could indicate an effect of other climate variables (e.g. late frost) or biotic stressors such as insect outbreaks. Furthermore, we found that RWI was lower in the year after a climate extreme occurred in the late summer. Most likely due to the gradual increase in temperature and more frequent drought we found negative trends in RWI and EVI. EVI maps could indicate where beech is sensitive to climate changes and could be used for planning mitigation interventions. Logical next steps should focus on a tree-based understanding of the short -and long-term effects of climate extremes on tree growth and survival, taking into account differential carbon allocation to the crown (EVI) and to wood-based variables. This research highlights the value of an integrated approach for upscaling tree-based knowledge to the forest level

Lipid-mediated Wnt protein stabilization enables serum-free culture of human organ stem cells

Wnt signalling proteins are essential for culture of human organ stem cells in organoids, but most Wnt protein formulations are poorly active in serum-free media. Here we show that purified Wnt3a protein is ineffective because it rapidly loses activity in culture media due to its hydrophobic nature, and its solubilization requires a detergent, CHAPS (3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate), that interferes with stem cell self-renewal. By stabilizing the Wnt3a protein using phospholipids and cholesterol as carriers, we address both problems: Wnt activity remains stable in serum-free media, while non-toxic carriers allow the use of high Wnt concentrations. Stabilized Wnt3a supports strongly increased self-renewal of organ and embryonic stem cells and the serum-free establishment of human organoids from healthy and diseased intestine and liver. Moreover, the lipophilicity of Wnt3a protein greatly facilitates its purification. Our findings remove a major obstacle impeding clinical applications of adult stem cells and offer advantages for all cell culture uses of Wnt3a protein

Mouse Model of Alagille Syndrome and Mechanisms of Jagged1 Missense Mutations.

BACKGROUND & AIMS: Alagille syndrome is a genetic disorder characterized by cholestasis, ocular abnormalities, characteristic facial features, heart defects, and vertebral malformations. Most cases are associated with mutations in JAGGED1 (JAG1), which encodes a Notch ligand, although it is not clear how these contribute to disease development. We aimed to develop a mouse model of Alagille syndrome to elucidate these mechanisms. METHODS: Mice with a missense mutation (H268Q) in Jag1 (Jag1+/Ndr mice) were outbred to a C3H/C57bl6 background to generate a mouse model for Alagille syndrome (Jag1Ndr/Ndr mice). Liver tissues were collected at different timepoints during development, analyzed by histology, and liver organoids were cultured and analyzed. We performed transcriptome analysis of Jag1Ndr/Ndr livers and livers from patients with Alagille syndrome, cross-referenced to the Human Protein Atlas, to identify commonly dysregulated pathways and biliary markers. We used species-specific transcriptome separation and ligand-receptor interaction assays to measure Notch signaling and the ability of JAG1Ndr to bind or activate Notch receptors. We studied signaling of JAG1 and JAG1Ndr via NOTCH 1, NOTCH2, and NOTCH3 and resulting gene expression patterns in parental and NOTCH1-expressing C2C12 cell lines. RESULTS: Jag1Ndr/Ndr mice had many features of Alagille syndrome, including eye, heart, and liver defects. Bile duct differentiation, morphogenesis, and function were dysregulated in newborn Jag1Ndr/Ndr mice, with aberrations in cholangiocyte polarity, but these defects improved in adult mice. Jag1Ndr/Ndr liver organoids collapsed in culture, indicating structural instability. Whole-transcriptome sequence analyses of liver tissues from mice and patients with Alagille syndrome identified dysregulated genes encoding proteins enriched at the apical side of cholangiocytes, including CFTR and SLC5A1, as well as reduced expression of IGF1. Exposure of Notch-expressing cells to JAG1Ndr, compared with JAG1, led to hypomorphic Notch signaling, based on transcriptome analysis. JAG1-expressing cells, but not JAG1Ndr-expressing cells, bound soluble Notch1 extracellular domain, quantified by flow cytometry. However, JAG1 and JAG1Ndr cells each bound NOTCH2, and signaling from NOTCH2 signaling was reduced but not completely inhibited, in response to JAG1Ndr compared with JAG1. CONCLUSIONS: In mice, expression of a missense mutant of Jag1 (Jag1Ndr) disrupts bile duct development and recapitulates Alagille syndrome phenotypes in heart, eye, and craniofacial dysmorphology. JAG1Ndr does not bind NOTCH1, but binds NOTCH2, and elicits hypomorphic signaling. This mouse model can be used to study other features of Alagille syndrome and organ development

Quantifying the effect of forest age in annual net forest carbon balance

Forests dominate carbon (C) exchanges between the terrestrial biosphere and the atmosphere on land. In the long term, the net carbon flux between forests and the atmosphere has been significantly impacted by changes in forest cover area and structure due to ecological disturbances and management activities. Current empirical approaches for estimating net ecosystem productivity (NEP) rarely consider forest age as a predictor, which represents variation in physiological processes that can respond differently to environmental drivers, and regrowth following disturbance. Here, we conduct an observational synthesis to empirically determine to what extent climate, soil properties, nitrogen deposition, forest age and management influence the spatial and interannual variability of forest NEP across 126 forest eddy-covariance flux sites worldwide. The empirical models explained up to 62% and 71% of spatio-temporal and across-site variability of annual NEP, respectively. An investigation of model structures revealed that forest age was a dominant factor of NEP spatio-temporal variability in both space and time at the global scale as compared to abiotic factors, such as nutrient availability, soil characteristics and climate. These findings emphasize the importance of forest age in quantifying spatio-temporal variation in NEP using empirical approaches

Long-term culture of genome-stable bipotent stem cells from adult human liver.

Despite the enormous replication potential of the human liver, there are currently no culture systems available that sustain hepatocyte replication and/or function in vitro. We have shown previously that single mouse Lgr5+ liver stem cells can be expanded as epithelial organoids in vitro and can be differentiated into functional hepatocytes in vitro and in vivo. We now describe conditions allowing long-term expansion of adult bile duct-derived bipotent progenitor cells from human liver. The expanded cells are highly stable at the chromosome and structural level, while single base changes occur at very low rates. The cells can readily be converted into functional hepatocytes in vitro and upon transplantation in vivo. Organoids from α1-antitrypsin deficiency and Alagille syndrome patients mirror the in vivo pathology. Clonal long-term expansion of primary adult liver stem cells opens up experimental avenues for disease modeling, toxicology studies, regenerative medicine, and gene therapy.This work was supported by grants to MH (EU/236954) and to HC (The United European Gastroenterology Federation (UEGF) Research Prize 2010, EU/232814-StemCellMark and NWO/116002008). MH is supported by The Wellcome Trust Sir Henry Dale fellowship. The Rspo cell line was kindly provided by Dr. Calvin Kuo.This is the final published version. It first appeared at http://www.cell.com/abstract/S0092-8674%2814%2901566-9

Long-Term Adult Feline Liver Organoid Cultures for Disease Modeling of Hepatic Steatosis.

Hepatic steatosis is a highly prevalent liver disease, yet research is hampered by the lack of tractable cellular and animal models. Steatosis also occurs in cats, where it can cause severe hepatic failure. Previous studies demonstrate the potential of liver organoids for modeling genetic diseases. To examine the possibility of using organoids to model steatosis, we established a long-term feline liver organoid culture with adult liver stem cell characteristics and differentiation potential toward hepatocyte-like cells. Next, organoids from mouse, human, dog, and cat liver were provided with fatty acids. Lipid accumulation was observed in all organoids and interestingly, feline liver organoids accumulated more lipid droplets than human organoids. Finally, we demonstrate effects of interference with β-oxidation on lipid accumulation in feline liver organoids. In conclusion, feline liver organoids can be successfully cultured and display a predisposition for lipid accumulation, making them an interesting model in hepatic steatosis research