Estimation of subsurface porosities and thermal conductivities of polygonal tundra by coupled inversion of electrical resistivity, temperature, and moisture content data

Studies indicate greenhouse gas emissions following permafrost thaw will amplify current rates of atmospheric warming, a process referred to as the permafrost carbon feedback. However, large uncertainties exist regarding the timing and magnitude of the permafrost carbon feedback, in part due to uncertainties associated with subsurface permafrost parameterization and structure. Development of robust parameter estimation methods for permafrost-rich soils is becoming urgent under accelerated warming of the Arctic. Improved parameterization of the subsurface properties in land system models would lead to improved predictions and a reduction of modeling uncertainty. In this work we set the groundwork for future parameter estimation (PE) studies by developing and evaluating a joint PE algorithm that estimates soil porosities and thermal conductivities from time series of soil temperature and moisture measurements and discrete in-time electrical resistivity measurements. The algorithm utilizes the Model-Independent Parameter Estimation and Uncertainty Analysis toolbox and coupled hydrological-thermal-geophysical modeling. We test the PE algorithm against synthetic data, providing a proof of concept for the approach. We use specified subsurface porosities and thermal conductivities and coupled models to set up a synthetic state, perturb the parameters, and then verify that our PE method is able to recover the parameters and synthetic state. To evaluate the accuracy and robustness of the approach we perform multiple tests for a perturbed set of initial starting parameter combinations. In addition, we varied types and quantities of data to better understand the optimal dataset needed to improve the PE method. The results of the PE tests suggest that using multiple types of data improve the overall robustness of the method. Our numerical experiments indicate that special care needs to be taken during the field experiment setup so that (1) the vertical distance between adjacent measurement sensors allows the signal variability in space to be resolved and (2) the longer time interval between resistivity snapshots allows signal variability in time to be resolved

Safety and efficacy of Riluzole in Acute Spinal Cord Injury Study (RISCIS): A multi-center, randomized, placebo-controlled, double-blinded trial

Riluzole is a sodium-glutamate antagonist that attenuates neurodegeneration in amyotrophic lateral sclerosis (ALS). It has shown favorable results in promoting recovery in pre-clinical models of traumatic spinal cord injury (tSCI) and in early phase clinical trials. This study aimed to evaluate the efficacy and safety of riluzole in acute cervical tSCI. An international, multi-center, prospective, randomized, double-blinded, placebo-controlled, adaptive, Phase III trial (NCT01597518) was undertaken. Patients with American Spinal Injury Association Impairment Scale (AIS) A-C, cervical (C4-C8) tSCI, and \u3c12 h from injury were randomized to receive either riluzole, at an oral dose of 100 mg twice per day (BID) for the first 24 h followed by 50 mg BID for the following 13 days, or placebo. The primary efficacy end-point was change in Upper Extremity Motor (UEM) scores at 180 days. The primary efficacy analyses were conducted on an intention to treat (ITT) and completed cases (CC) basis. The study was powered at a planned enrolment of 351 patients. The trial began in October 2013 and was halted by the sponsor on May 2020 (and terminated in April 2021) in the face of the global COVID-19 pandemic. One hundred ninety-three patients (54.9% of the pre-planned enrolment) were randomized with a follow-up rate of 82.7% at 180 days. At 180 days, in the CC population the riluzole-treated patients compared with placebo had a mean gain of 1.76 UEM scores (95% confidence interval: -2.54-6.06) and 2.86 total motor scores (CI: -6.79-12.52). No drug-related serious adverse events were associated with the use of riluzole. Additional pre-planned sensitivity analyses revealed that in the AIS C population, riluzole was associated with significant improvement in total motor scores (estimate: standard error [SE] 8.0; CI 1.5-14.4) and upper extremity motor scores (SE 13.8; CI 3.1-24.5) at 6 months. AIS B patients had higher reported independence, measured by the Spinal Cord Independence Measure score (45.3 vs. 27.3; d: 18.0 CI: -1.7-38.0) and change in mental health scores, measured by the Short Form 36 mental health domain (2.01 vs. -11.58; d: 13.2 CI: 1.2-24.8) at 180 days. AIS A patients who received riluzole had a higher average gain in neurological levels at 6 months compared with placebo (mean 0.50 levels gained vs. 0.12 in placebo; d: 0.38, CI: -0.2-0.9). The primary analysis did not achieve the predetermined end-point of efficacy for riluzole, likely related to insufficient power. However, on pre-planned secondary analyses, all subgroups of cervical SCI subjects (AIS grades A, B and C) treated with riluzole showed significant gains in functional recovery. The results of this trial may warrant further investigation to extend these findings. Moreover, guideline development groups may wish to assess the possible clinical relevance of the secondary outcome analyses, in light of the fact that SCI is an uncommon orphan disorder without an accepted neuroprotective treatment