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Sand patches are one of the precursors to early stage protodunes and occur widely in both desert and coastal aeolian environments. Here we show field evidence of a mechanism to explain the initiation of sand patches on non‐erodible surfaces, such as desert gravels and moist beaches. Changes in sand transport dynamics, directly associated with the height of the saltation layer and variable transport law, observed at the boundary between non‐erodible and erodible surfaces lead to sand deposition on the erodible surface. This explains how sand patches can form on surfaces with limited sand availability where linear stability of dune theory does not apply. This new mechanism is supported by field observations that evidence both the change in transport rate over different surfaces and in situ patch formation that leads to modification of transport dynamics at the surface boundary. Plain Language Summary Sand patches can be observed in various environments such as beaches and gravel plains in deserts. Expected to be precursors of dunes when sediment supply is limited, these bedforms are typically a few centimeters high and present a reverse longitudinal elevation profile, with a sharp upwind edge and a smooth downwind tail. Based on field measurements, we propose a formation mechanism for these patches associated with the sensitive nature of wind‐blown sand transport to changing bed conditions: sand saltation is reduced at the transition from a solid to an erodible surface, hence favoring deposition on the patches. This allows us to explain their typical meter‐scale length as well as their asymmetric shapes. Key Points Sand patches can emerge on non‐erodible surfaces Differing surfaces characteristics control particle behavior Field measurements demonstrate the key role of sand transport in bedform initiation

BackgroundThe Osteoarthritis Initiative (OAI) is the largest knee osteoarthritis observational cohort. It provides the possibility to study the evolution of OA structural changes over time and the associated risk factors. It also allows the potential disease-modifying OA drug effects to be explored in patients over time.ObjectivesThis study aimed to examine, for the first time, the long-term (6-year) protective effect of combined glucosamine (Glu) and chondroitin sulfate (CS) treatment on OA knee cartilage volume using the OAI cohort.MethodsParticipants from the OAI Progression and Incidence sub-cohorts who had MRI data on the target knee at baseline and at 6 years and with a JSW greater than 1 mm, and information on the Glu/CS consumption were included (n=1593). The participants were stratified into two main groups based on whether or not they had medial meniscal extrusion at baseline, and the former group (n=429) were further stratified into subgroups based on their exposure time: not exposed, 1 year, 2 to 3 years, and 4 to 6 years. MRI assessments were done using fully automated quantitative technologies1,2. Statistical analysis included the Jonckheere-Terpstra trend test as well as multivariate analysis test.ResultsFindings indicate that in participants with knee OA, treatment with the combined Glu/CS significantly reduced the loss of cartilage in the global knee associated with the lateral compartment. Moreover, the extent of the treatment's positive effect was also found to be related to the exposure time to treatment, the protective effect at 6 years being significant in participants who were exposed to 2 or more years of treatment.ConclusionsThe findings of this study are in line with previous data showing chondroprotective effects of glucosamine and chondroitin sulfate treatment with preferential effects, and provide future support for the long-term structure-modifying effects of such treatment in knee osteoarthritis subjects.ReferencesDodin P, Pelletier JP, Martel-Pelletier J, Abram F. IEEE Trans Biomed Eng. 2010;57:2699–711.Dodin P, Abram F, Pelletier JP, Martel-Pelletier J. J Biomed Graph Comput. 2013;3:51–65.Disclosure of InterestJ. Marte-Pelletier Shareholder of: Arthrolab Inc., Grant/research support from: Bioiberica, Consultant for: Bioiberica, J. P. Raynauld: None declared, F. Abram: None declared, P. Delorme: None declared, J. P. Pelletier Shareholder of: Arthrolab Inc., Grant/research support from: Bioiberica, Consultant for: Bioiberica, Speakers bureau: Bioiberica

Background The Osteoarthritis Initiative (OAI) is the largest knee osteoarthritis (OA) observational cohort. It provides the possibility to study the evolution of OA structural changes over time and the associated risk factors. It also allows the potential disease-modifying OA drug (DMOAD) effects to be explored in patients over time. Objectives To determine, using data from participants enrolled in the progression cohort of the OAI, the effects of existing meniscal extrusion on the extent of cartilage loss and structural changes over time, and response to pharmacological treatment including the combination of glucosamine and chondroitin sulfate (Glu/CS). Methods Knee OA patients were stratified based on the presence/absence of medial meniscal extrusion at baseline and on whether or not they received conventional OA pharmacological treatment (analgesics/non-steroidal anti-inflammatory drugs [NSAIDs]) and/or Glu/CS for 24 consecutive months. The main outcomes were knee structural changes including the cartilage volume measured by quantitative magnetic resonance imaging (MRI) and of loss of joint space width (JSW). Results Participants reported taking (+) (n=300) or not taking (−) (n=300) OA treatment (analgesics/NSAIDs). The participants with meniscal extrusion had more severe disease at baseline. In the −analgesics/NSAIDs group with meniscal extrusion, participants taking Glu/CS had significantly reduced loss of cartilage volume at 24 months in the medial tibiofemoral compartment (p=0.02) and lateral plateau (p=0.05). No effect of Glu/CS was observed in patients without extrusion. In the +analgesic/NSAIDs group without meniscal extrusion, those taking Glu/CS had significantly reduced loss of cartilage volume in the global knee (p=0.055), medial compartment (p=0.05), lateral plateau (p=0.007), and trochlea (p=0.04). No effect of Glu/CS treatment occurred in participants with extrusion. No significant reduction in JSW was found between those taking (+) and not taking (−) Glu/CS treatment. Conclusions This study confirms that combined administration of Glu/CS has significant protective effects on structure in knee OA. The presence of meniscal extrusion was found to be an important factor that can influence the drug effect on cartilage volume. X-rays were found to be much less sensitive than MRI at documenting the protective effect of treatment on structural changes. Disclosure of Interest : J.-P. Pelletier Shareholder of: ArthroLab Inc., Consultant for: Bioiberica, C. Roubille: None declared, F. Abram Employee of: ArthroLab Inc., P. Delorme: None declared, J.-P. Raynauld Consultant for: ArthroLab Inc., J. Martel-Pelletier Shareholder of: ArthroLab Inc., Consultant for: Bioiberica DOI 10.1136/annrheumdis-2014-eular.2248

Background Knee osteoarthritis (OA) structural changes are complex and comprise cartilage volume loss as well as meniscal lesions, which were shown to promote cartilage loss. Recently, strontium ranelate (SrRan) was demonstrated to have DMOAD properties(1,2). Objectives We thus further evaluated the role of meniscal extrusion (mExt) on knee OA progression and its impact on response to SrRan treatment assessed by X-rays (change in joint space width [JSW]) and qMRI (cartilage volume loss [CVL] in the medial compartment) at 36 months (M36) in subjects with (mExt+) or without (mExt) meniscal extrusion, in association (+) or not (-) with bone marrow lesions (BML). Methods Patients from the qMRI substudy of the SrRan Efficacy in Knee OsteoarthrItis triAl (SEKOIA) (modified intention-to-treat, n=330) were stratified based on whether mExt (mExt+, n=60; mExt-, n=270) and BML were present or not (BML+, n=84; BML-, n=246) and on their association in the medial compartment at baseline. CVL was assessed by qMRI and JSW by X-rays at baseline and M36. Results In the placebo group, mExt+ patients demonstrated significantly more JSW loss (-0.76±0.67 mm; p=0.002) and CVL in the medial compartment (-10.40±4.23%; p=0.0005) than mExt- patients (-0.35±0.61 mm and -7.60±4.63%, respectively). mExt-/BML+ patients (n=18) had significantly more JSW loss (-0.77±0.68 mm; p=0.003) and a trend (-9.57±5.29%; p=0.090) toward more CVL compared to mExt-/BML- patients (n=68) (-0.23±0.55 mm and -7.08±4.33%, respectively). mExt+/BML+ patients (n=12) had a trend toward more CVL in the medial compartment (-11.22±1.90%; p=0.103) than mExt+/BML- (n=14) (-9.69±5.50%), while JSW change showed no difference. Importantly, the JSW loss and CVL in the medial compartment were greater when mExt and BML were both present simultaneously in this compartment. In mExt+ patients, while no difference was found in the JSW loss between groups, SrRan at 2 g/day reduced the CVL in the plateaus (-5.74±3.54%; p=0.007) and a trend toward a decrease in the medial plateaus (-4.90±5.19%; p=0.081) compared to the placebo (-10.01±5.79% and -9.07±8.74% respectively). In the mExt+/BML+ patients, SrRan 2 g/day significantly reduced the CVL in the medial plateaus (-1.13±2.24% vs -11.45±4.47% for the placebo; p=0.046), whereas there was no difference for the JSW loss. Conclusions The progression of knee OA assessed both by X-rays and qMRI was greater in mExt+ patients, and was further increased when co-localized with BML. Based on qMRI, SrRan 2 g/day showed beneficial DMOAD structural effects in mExt+ and mExt+/BML+ patients, targeting a subpopulation at higher risk of knee OA progression, while JSW loss was not sensitive enough to provide evidence of such effects. References Reginster JY. et al. Ann Rheum Dis 2013;72:179-86. Pelletier JP et al. Ann Rheum Dis. 2013 Dec 2. doi: 10.1136/annrheumdis-2013-203989. Disclosure of Interest C. Roubille: None declared, J. Martel-Pelletier Shareholder of: ArthroLab Inc., F. Abram Employee of: ArthroLab Inc., M. Dorais Consultant for: ArthroLab Inc., P. Delorme: None declared, J.-P. Raynauld Consultant for: ArthroLab Inc., J.-P. Pelletier Shareholder of: ArthroLab Inc. DOI 10.1136/annrheumdis-2014-eular.2539

Objectives To explore using quantitative magnetic resonance imaging (qMRI) the disease modifying effect of strontium ranelate (SrRan) treatment on the cartilage volume loss and bone marrow lesions (BMLs) in a subgroup of patients from a Phase III clinical trial on human knee osteoarthritis (OA) (SEKOIA). Methods Patients with primary symptomatic knee OA were randomized to receive either SrRan 1 g or 2 g/day or placebo. MRI was performed at baseline, 12, 24, and 36 months. The changes in knee cartilage volume loss and BMLs were assessed in the global joint and subregions. Missing values were imputed and the analyses were adjusted according to Bonferroni. Results In the subgroup of patients with MRI, the distribution of patients (n=330) was 113, 105, and 112 for SrRan 1 g/day, 2 g/day, and placebo, respectively. There were no between-group differences at baseline with regard to demographics, clinical symptoms, or imaging characteristics. Treatment with SrRan at 2 g/day significantly decreased the loss of cartilage volume on the tibial plateau at 12 (p=0.002) and 36 months (M36) (p=0.003). At M36, in patients with BML at baseline, the BML score decreased in the two treatment groups compared to an increase in the placebo group in the medial compartment (p=0.002 and p=0.001 in the SrRan 1 g/day and 2 g/day groups, respectively). In those patients, SrRan 2 g/day significantly (p=0.023) decreased the cartilage loss at M36 in the medial tibial plateau compared to placebo, whereas SrRan 1 g/day did not (p=0.763). Conclusions In knee OA patients, treatment with SrRan 2 g/day was found to have a beneficial effect both on cartilage and subchondral bone by significantly reducing the cartilage volume loss in the tibial plateau and the progression of BML in the medial compartment. Disclosure of Interest J. Martel-Pelletier Shareholder of: ArthroLab Inc, Grant/research support from: Servier, Consultant for: Servier, ArthroLab Inc, C. Roubille: None Declared, J.-P. Raynauld Consultant for: ArthroLab Inc, F. Abram Employee of: ArthroLab Inc., M. Dorais: None Declared, P. Delorme: None Declared, J.-P. Pelletier Shareholder of: ArthroLab Inc, Grant/research support from: Servier, Consultant for: Servier, ArthroLab Inc

Precipitation is the most important driver of the hydrological cycle, but it is challenging to estimate it over large scales from satellites and models. Here, we assessed the performance of six global and quasi-global high-resolution precipitation datasets (European Centre for Medium-Range Weather Forecasts (ECMWF) Reanalysis version 5 (ERA5), Climate Hazards group Infrared Precipitation with Stations version 2.0 (CHIRPS), Multi-Source Weighted-Ensemble Precipitation version 2.80 (MSWEP), TerraClimate (TERRA), Climate Prediction Centre Unified version 1.0 (CPCU), and Precipitation Estimation from Remotely Sensed Information using Artificial Neural Networks-Cloud Classification System-Climate Data Record (PERSIANN-CCS-CDR, hereafter PERCCDR) for hydrological modelling globally and quasi-globally. We forced the WBMsed global hydrological model with the precipitation datasets to simulate river discharge from 1983 to 2019 and evaluated the predicted discharge against 1825 hydrological stations worldwide, using a range of statistical methods. The results show large differences in the accuracy of discharge predictions when using different precipitation input datasets. Based on evaluation at annual, monthly, and daily timescales, MSWEP followed by ERA5 demonstrated a higher correlation (CC) and Kling–Gupta efficiency (KGE) than other datasets for more than 50 % of the stations, whilst ERA5 was the second-highest-performing dataset, and it showed the highest error and bias for about 20 % of the stations. PERCCDR is the least-well-performing dataset, with a bias of up to 99 % and a normalised root mean square error of up to 247 %. PERCCDR only show a higher KGE and CC than the other products for less than 10 % of the stations. Even though MSWEP provided the highest performance overall, our analysis reveals high spatial variability, meaning that it is important to consider other datasets in areas where MSWEP showed a lower performance. The results of this study provide guidance on the selection of precipitation datasets for modelling river discharge for a basin, region, or climatic zone as there is no single best precipitation dataset globally. Finally, the large discrepancy in the performance of the datasets in different parts of the world highlights the need to improve global precipitation data products.

Objectives To explore the effects of commonly used medications for treatment of knee osteoarthritis (OA) on structural progression. Methods Participants (n=600) were selected from the Osteoarthritis Initiative (OAI) progression cohort (http://www.oai.ucsf.edu/) (n=1,390) who met the following criteria: 24 consecutive months of follow-up with clinical and imaging data including radiographs and magnetic resonance imaging (MRI) of the index (highest WOMAC pain) knee. Data for joint space width (JSW) were obtained from the OAI database and cartilage volume was measured using fully-automated MRI. Results Participants reported taking (+) (n=300) or not taking (-) (n=300) OA treatment (analgesic/NSAID) over 24 months, with or without glucosamine and chondroitin sulfate (Glu/CS). The +analgesic/NSAID subjects had higher WOMAC scores (p<0.0001) and smaller JSW (p=0.013) reflecting more severe disease at baseline. In the -analgesic/NSAID group, subjects taking Glu/CS had a smaller loss of JSW at 12 months (p=0.057) and cartilage volume at 24 months in the medial central tibial plateau (p=0.022 univariate and p=0.025 multivariate analysis). In the +analgesic/NSAID group, the subjects taking Glu/CS had significantly lower WOMAC scores (pain, p<0.0001; stiffness, p=0.0373; disability, p=0.0004) and higher KOOS scores at baseline as well as a smaller cartilage volume loss in the tibial plateau at both 12 (p=0.029) and 24 months (p=0.033). In the -analgesic/NSAID groups, those who took Glu/CS and had JSW at baseline higher than the median showed less cartilage volume loss at 24 months in the medial compartment (p=0.025) and condyle (p=0.01). Conclusions In both the +analgesic/NSAID and -analgesic/NSAID groups, participants who took Glu/CS had reduced loss of JSW and cartilage volume over 24 months. These effects of Glu/CS on structural changes support results from previous studies. Disclosure of Interest None Declared

Objective To explore, using MRI, the disease-modifying effect of strontium ranelate (SrRan) treatment on cartilage volume loss (CVL) and bone marrow lesions (BMLs) in a subset of patients from a Phase III clinical trial in knee osteoarthritis (OA) (SrRan Efficacy in Knee OsteoarthrItis triAl (SEKOIA)). Material and methods Patients with primary symptomatic knee OA were randomised to receive either SrRan 1 g/day or 2 g/day or placebo (SEKOIA study). A subset of these patients had MRIs at baseline, 12, 24 and 36 months to assess the knee cartilage volume and BMLs. Missing values were imputed and the analyses were adjusted according to Bonferroni. Results In this MRI subset, the distribution of patients (modified intention-to-treat; n=330) was 113, 105 and 112 for SrRan 1 g/day, 2 g/day and placebo, respectively. The groups were fairly balanced at baseline regarding demographics, clinical symptoms or imaging characteristics. Treatment with SrRan 2 g/day significantly decreased CVL on the plateaus at 12 (p=0.002) and 36 (p=0.003) months compared with placebo. Of note, in the medial femur and plateau, SrRan 1 g/day, but not SrRan 2 g/day, had more CVL than placebo. In patients with BML in the medial compartment at baseline, the BML score at 36 months was decreased in both treatment groups compared with the placebo group (SrRan 1 g/day, p=0.002 and SrRan 2 g/day p=0.001, respectively), and CVL significantly decreased with SrRan 2 g/day (p=0.023) in the plateau compared with placebo. Conclusions In knee OA patients, treatment with SrRan 2 g/day was found to have beneficial effects on structural changes by significantly reducing CVL in the plateau and BML progression in the medial compartment.

Background There is an obvious need to identify biomarkers that could predict patient response to an osteoarthritis (OA) treatment. This post hoc study explored in a 2-year randomized controlled trial in patients with knee OA, the likelihood of some serum biomarkers to be associated with a better response to chondroitin sulfate in reducing cartilage volume loss. Methods Eight biomarkers were studied: hyaluronic acid (HA), C reactive protein (CRP), adipsin, leptin, N-terminal propeptide of collagen IIα (PIIANP), C-terminal crosslinked telopeptide of type I collagen (CTX-1), matrix metalloproteinase-1 (MMP-1), and MMP-3. Patients were treated with chondroitin sulfate (1200 mg/day; n  = 57) or celecoxib (200 mg/day; n  = 62). Serum biomarkers were measured at baseline. The cartilage volume at baseline and its loss at 2 years were assessed by quantitative magnetic resonance imaging (MRI). Statistical analysis included analysis of covariance. Results As data from the original MOSAIC trial showed no differences in cartilage volume and loss in the lateral compartment of the knee joint between the two treatment groups in any comparison, only the medial compartment and its subregions were studied. Stratification according to the median biomarker levels was used to discriminate treatment effect. In patients with levels of biomarkers of inflammation (HA, leptin and adipsin) lower than the median, those treated with chondroitin sulfate demonstrated less cartilage volume loss in the medial compartment, condyle, and plateau ( p  ≤ 0.047). In contrast, patients treated with chondroitin sulfate with higher levels of MMP-1 and MMP-3, biomarkers of cartilage catabolism, had less cartilage volume loss in the medial compartment, condyle, and plateau ( p  ≤ 0.050). Patients with higher levels of PIIANP and CTX-1, biomarkers related to collagen anabolism and bone catabolism, respectively, had reduced cartilage volume loss in the medial condyle ( p  ≤ 0.026) in the chondroitin sulfate group. Conclusion This study is suggestive of a potentially greater response to chondroitin sulfate treatment on cartilage volume loss in patients with knee OA with low level of inflammation and/or greater level of cartilage catabolism. Trial registration This is a post hoc study. Original trial registration: ClinicalTrials.gov, NCT01354145 . Registered on 13 May 2011. 

Following a scheme suggested by B. Feigon, we investigate a local relative trace formula in the situation of a reductive pp-adic group GG relative to a symmetric subgroup H=H_(F)H= \\underline {H}(\\mathrm {F}) where H_\\underline {H} is split over the local field F\\mathrm {F} of characteristic zero and G=G_(F)G = \\underline {G} (\\mathrm {F}) is the restriction of scalars of H_/E\\underline {H} _{/\\mathrm {E}} relative to a quadratic unramified extension E\\mathrm {E} of F\\mathrm {F}. We adapt techniques of the proof of the local trace formula by J. Arthur in order to get a geometric expansion of the integral over H×HH \\times H of a truncated kernel associated to the regular representation of GG.