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Abstract Background Secondary anterior cruciate ligament (ACL) ruptures are a relevant clinical concern after surgical treatment of a primary ACL rupture. However, there is a lack of scientific evidence related to the role of muscle strength prior to revision surgery in a second ACL rupture. The aim of this study was to assess differences in knee extensor and flexor strength in patients before primary and secondary ACL reconstruction compared to healthy controls. Methods In total, n = 69 age, weight and sex matched individuals were included in the study: n = 23 patients with isolated primary ACL rupture, n = 23 with secondary ACL rupture, and n = 23 matched healthy controls. Maximal isokinetic knee extension and flexion torque normalized to body mass was assessed for both legs. Results For patients with secondary ACL ruptures, torques were reduced in the non-injured (extension: 1.94 Nm/kg vs. 2.46 Nm/kg, p

Assimilating either soil moisture or streamflow individually has been well demonstrated to enhance the simulation performance of hydrological models. However, the runoff routing process may introduce a lag between soil moisture and outlet discharge, presenting challenges in simultaneously assimilating the two types of observations into a hydrological model. The asynchronous ensemble Kalman filter (AEnKF), an adaptation of the ensemble Kalman filter (EnKF), is capable of utilizing observations from both the assimilation moment and the preceding periods, thus holding potential to address this challenge. Our study first merges soil moisture data collected from field soil moisture monitoring sites with China Meteorological Administration Land Data Assimilation System (CLDAS) soil moisture data. We then employ the AEnKF, equipped with improved error models, to assimilate both the observed outlet discharge and the merged soil moisture data into the Xin'anjiang model. This process updates the state variables of the model, aiming to enhance real-time flood forecasting performance. Tests involving both synthetic and real-world cases demonstrates that assimilation of these two types of observations simultaneously substantially reduces the accumulation of past errors in the initial conditions at the start of the forecast, thereby aiding in elevating the accuracy of flood forecasting. Moreover, the AEnKF with the enhanced error model consistently yields greater forecasting accuracy across various lead times compared to the standard EnKF. [ABSTRACT FROM AUTHOR]

Groundwater is under pressure from a changing climate and increasing anthropogenic demands. In this study, we project the effect of these two processes onto future groundwater status. Climate projections of Representative Concentration Pathway 4.5 (RCP4.5) and Representative Concentration Pathway 8.5 (RCP8.5) from the Coupled Model Intercomparison Project Phase 6 (CMIP6) drive a one-way coupled fully distributed hydrological and groundwater model. In addition, three plausible groundwater abstraction scenarios with diverging predictions from increasing, constant, and decreasing volumes and spatial distributions are used. Groundwater status projections are assessed for short-term (2030), mid-term (2050), and long-term (2100) periods. We use the Bandung groundwater basin as our case study; it is located 120 km from the current capital city of Indonesia, Jakarta, which is currently scheduled for relocation. It is selected as the future anthropogenic uncertainties in the basin, related to the projected groundwater abstraction, are in agreement with our developed scenarios. Results show that changes in the projected climate input, including intensifying rainfall and rising temperature, do not propagate notable changes in groundwater recharge. At the current unsustainable groundwater abstraction rate, the confined piezometric heads are projected to drop by maxima of 7.14, 15.25, and 29.51 m in 2030, 2050, and 2100, respectively. When groundwater abstraction expands in proportion to present population growth, the impact is worsened almost 2-fold. In contrast, if groundwater abstraction decreases because of the relocated capital city, groundwater storage starts to show replenishment potential. As a whole, projected groundwater status changes are dominated by anthropogenic activity and less so by changes in climatic forcing. The results of this study are expected to show and inform responsible parties in operational water management about the issue of the impact of projected climate forcing and anthropogenic activity on future groundwater status. [ABSTRACT FROM AUTHOR]

Purpose: Previous evidence indicated that the tibiofemoral bone configuration might elevate the risk of an anterior cruciate ligament (ACL) injury. Furthermore, a low hamstring‐to‐quadriceps muscle ratio predisposes especially females to unfavourable knee kinematics. The primary objective of the present study was to investigate sex‐specific associations between tibiofemoral bone geometry and isokinetic knee flexion torque in patients with primary ACL injury followed by ACL reconstruction. Methods: N = 100 patients (72 = male, 28 = female, age = 31.3 ± 10.2, body mass index = 25.3 ± 3.6) with primary ACL rupture with isokinetic knee flexion torque assessments before and 6 months after ACL reconstruction surgery were analysed. Magnetic resonance imaging scans were analysed for medial posterior tibial slope (MPTS) and lateral posterior tibial slope, notch width index (NWI) and lateral femoral condyle index (LFCI). Additionally, isokinetic knee flexion torque (60°/s) and hamstring–quadriceps ratios were evaluated. Subsequently, functional parameters were correlated with imaging data for gender subgroups. Results: The findings showed that presurgical isokinetic knee flexion torque was not associated with any marker of femoral or tibial bone geometry. Further, while significant differences were observed between female (0.883 ± 0.31 Nm/kg) and male (1.18 ± 0.35 Nm/kg) patients regarding preoperative normalized knee flexion torque (p < 0.001), no significant sex differences were found for percentage increases in normalized knee flexion torque from presurgery to postsurgery. Generally, female patients demonstrated significantly higher MPTS magnitudes (p < 0.05) and lower LFCI values (p < 0.05) compared to men. Conclusion: The present results demonstrated no association between tibial or femoral bone geometry and muscle strength of the hamstrings in patients with ACL reconstruction, indicating an important mismatch of muscular compensation to deviations in bone geometry. There were no sex‐specific differences in tibiofemoral bone parameters. Level of Evidence: Level III. [ABSTRACT FROM AUTHOR]

Mohammad Arafat,1 Yunmei Song,1 Kyle Brewer,2 Paris Fouladian,1 Ankit Parikh,1 Hugo Albrecht,3 Anton Blencowe,2 Sanjay Garg1 1Pharmaceutical Innovation and Development (PIDG) Group, Clinical and Health Sciences, University of South Australia, Adelaide, SA, 5000, Australia; 2Applied Chemistry and Translational Biomaterials (ACTB) Group, Clinical and Health Sciences, University of South Australia, Adelaide, SA, 5000, Australia; 3Drug Discovery and Development Group, Clinical and Health Sciences, University of South Australia, Adelaide, SA, 5000, AustraliaCorrespondence: Sanjay GargPharmaceutical Innovation and Development (PIDG) Group, Clinical and Health Sciences, University of South Australia, Adelaide, SA, 5000, AustraliaEmail Sanjay.Garg@unisa.edu.auAnton BlencoweApplied Chemistry and Translational Biomaterials (ACTB) Group, Clinical and Health Sciences, University of South Australia, Adelaide, SA, 5000, AustraliaEmail Anton.Blencowe@unisa.edu.auBackground: Drug-eluting gastrointestinal (GI) stents are emerging as promising platforms for the treatment of GI cancers and provide the combined advantages of mechanical support to prevent lumen occlusion and as a reservoir for localized drug delivery to tumors. Therefore, in this work we present a detailed quality assurance study of 5-fluorouracil (5FU) drug-eluting stents (DESs) as potential candidates for the treatment of obstructive GI cancers.Methods: The 5FU DESs were fabricated via a simple two-step sequential dip-coating process of commercial GI self-expanding nitinol stents with a 5FU-loaded polyurethane basecoat and a drug-free protective poly(ethylene-co-vinyl acetate) topcoat. The drug loading, content uniformity and drug stability were determined using a validated high-performance liquid chromatography (HPLC) method, which is also recommended in the United States Pharmacopeia. In vitro drug release studies were performed in phosphate buffered saline to determine the drug releasing properties of the two 5FU-loaded stents. Gas chromatography (GC) and HPLC were employed to determine total residual tetrahydrofuran and N,N-dimethylformamide in the stents remaining from the manufacturing process. Sterilization of the stents was performed using gamma radiation and stability testing was carried out for 3 months.Results: The drug loading analysis revealed excellent uniformity in the distribution of 5FU between and within individual stents. Determination of drug stability in the biorelevant release media confirmed that 5FU remains stable over 100 d. In vitro drug release studies from the stents revealed sustained release of 5FU across two different time scales (161 and 30 d), and mathematical modeling of drug release profiles revealed a diffusion-controlled mechanism for the sustained 5FU release. GC and HPLC analysis revealed that the daily residual solvent leached from the stents was below the United States (US) Food and Drug Administration (FDA) guidelines, and therefore, unlikely to cause localized/systemic toxicities. Sterilization of the stents with gamma radiation and accelerated stability tests over a period of 3 months revealed no significant effect on the stability or in vitro release of 5FU.Conclusion: Our results demonstrate that the 5FU DESs meet relevant quality standards and display favourable drug release characteristics for the potential treatment of GI cancers and related obstructions.Keywords: drug-eluting stent, 5-fluorouracil, gastrointestinal cancer, self-expanding metal stents

In the past decades significant progress has been made in the fitting of hydrologic models to data. Most of this work has focused on simple, CPU-efficient, lumped hydrologic models using discharge, water table depth, soil moisture, or tracer data from relatively small river basins. In this paper, we focus on large-scale hydrologic modeling and analyze the effect of parameter and rainfall data uncertainty on simulated discharge dynamics with the global hydrologic model PCR-GLOBWB. We use three rainfall data products; the CFSR reanalysis, the ERA-Interim reanalysis, and a combined ERA-40 reanalysis and CRU dataset. Parameter uncertainty is derived from Latin Hypercube Sampling (LHS) using monthly discharge data from five of the largest river systems in the world. Our results demonstrate that the default parameterization of PCR-GLOBWB, derived from global datasets, can be improved by calibrating the model against monthly discharge observations. Yet, it is difficult to find a single parameterization of PCR-GLOBWB that works well for all of the five river basins considered herein and shows consistent performance during both the calibration and evaluation period. Still there may be possibilities for regionalization based on catchment similarities. Our simulations illustrate that parameter uncertainty constitutes only a minor part of predictive uncertainty. Thus, the apparent dichotomy between simulations of global-scale hydrologic behavior and actual data cannot be resolved by simply increasing the model complexity of PCR-GLOBWB and resolving sub-grid processes. Instead, it would be more productive to improve the characterization of global rainfall amounts at spatial resolutions of 0.5° and smaller.

Ensemble projections of future changes in discharge over Europe show large variation. Several methods for performance-based weighting exist that have the potential to increase the robustness of the change signal. Here we use future projections of an ensemble of three hydrological models forced with climate datasets from the Coordinated Downscaling Experiment - European Domain (EURO-CORDEX). The experiment is set-up for nine river basins spread over Europe that hold different climate and catchment characteristics. We evaluate the ensemble consistency and apply two weighting approaches; the Climate model Weighting by Independence and Performance (ClimWIP) that focuses on meteorological variables and the Reliability Ensemble Averaging (REA) in our study applied to discharge statistics per basin. For basins with a strong climate signal, in Southern and Northern Europe, the consistency in the set of projections is large. For rivers in Central Europe the differences between models become more pronounced. Both weighting approaches assign high weights to single General Circulation Models (GCMs). The ClimWIP method results in ensemble mean weighted changes that differ only slightly from the non-weighted mean. The REA method influences the weighted mean more, but the weights highly vary from basin to basin. We see that high weights obtained through past good performance can provide deviating projections for the future. It is not apparent that the GCM signal dominates the overall change signal, i.e., there is no strong intra GCM consistency. However, both weighting methods favored projections from the same GCM.

Sanjay Tripathi,1 Ashish Nikhare,2 Gaurav Sharma,3 Tim Shea,4 Helmut Albrecht5 1Department of Pulmonary Medicine, Sheth LG General Hospital & AMC MET Medical College, Ahmedabad, India; 2Department of Pulmonology, Lata Mangeshkar Hospital, Nagpur, India; 3Regional Medical Affairs (South of Asia), Reckitt Benckiser, Haryana, India; 4Global Medical - Respiratory, Reckitt Benckiser, Parsippany, NJ, USA; 5Department of Cellular Biology & Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USACorrespondence: Tim SheaReckitt Benckiser, 399 Interpace Parkway, Parsippany, NJ 07054, USATel +1 973 404 2883Fax +1 201-573-6325Email Tim.Shea@rb.comPurpose: An extended-release (ER) formulation of the expectorant guaifenesin has recently been launched in India for the treatment of productive cough accompanied by mucus (phlegm). Although the safety profile of ER guaifenesin marketed in the USA is well documented, there were limited safety data available in the Indian population. The aim of this study was to further elucidate the safety profile of ER guaifenesin in patients with acute upper respiratory tract infection (URTI).Patients and methods: A prospective, post-marketing surveillance study enrolled 552 adults with cough, thickened mucus and chest congestion due to URTI, who took ER guaifenesin 1200 mg (Mucinex®, Reckitt Benckiser; two 600 mg tablets) every 12 hrs for 7 days. Adverse events (AEs) were recorded and questionnaires administered to patients and investigators.Results: A total of 29 treatment-emergent AEs were recorded in 28/552 patients, including gastrointestinal (n = 11), nervous system (n = 8), psychiatric (n = 3), respiratory, thoracic and mediastinal (n = 2), skin and subcutaneous tissue (n = 2), and general disorders (n = 3). All AEs were mild in severity and no serious AEs or deaths occurred. The majority of both patients and investigators were either satisfied or very satisfied with improvements in treatment outcomes.Conclusion: This study found that ER guaifenesin was well tolerated and had a favorable safety profile in otherwise healthy patients suffering from symptoms of cough, thickened mucus and chest congestion associated with URTI. Registered trial NCT03725085 (ClinicalTrials.gov) and CTRI/2014/07/004730 (ctri.nic.in).Keywords: expectorant, guaifenesin, Mucinex, post-marketing surveillance, safety profile, satisfaction