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Benefits, Costs, and Distributional Impacts of a Groundwater Trading Program in the Diamond Valley, Nevada
No full textIn Nevada’s Diamond Valley, unsustainable groundwater pumping has decreased the aquifer’s water level, raising irrigators’ pumping costs and threatening the viability of existing wells and springs. Continued extraction in excess of natural recharge will trigger a legally required curtailment of water rights in the valley, which was recently declared a critical management area (CMA). The extent of rights curtailment is not mandated, but it could be as high as 64%, the amount required to reach the estimated natural recharge rate. The default policy for curtailment of water rights will occur according to the principle of prior appropriation, whereby rights are revoked in reverse order of their date of issuance. Rights granted most recently will be canceled first, and the revocation will proceed in order of increasing seniority until the government’s desired level of total water extraction is reached. Nevada law requires this intervention to occur within 10 years of the CMA declaration. By law, irrigators and other stakeholders can propose alternative policies for reducing groundwater over-extraction. Because sudden rights curtailment could have detrimental economic impacts, such policies are under discussion. This report analyzes the economic outcomes of sudden and alternative curtailment policies. Using a hydro-economic model tailored to conditions in the region to examine alternative extraction scenarios, the analysis finds that, with no action, the depth to the water table will exceed 200 feet by 2045; with policy action, aquifer levels can be stabilized at 170–180 feet and at higher depths with more gradual curtailment. Across all policy scenarios, net agricultural profit is lowest under the default curtailment policy, and it increases with more gradual curtailment. Under curtailment, allowing parties to trade rights to extract water modestly increases economic benefits relative to no-trade alternatives
Debating as an Authority: Tullia d’Aragona’s Authorial Self-Fashioning and the ‘Tre Corone’
No full textOften celebrated as the first woman to enter the philosophical debate on the ethics of love, the sixteenth-century philosopher, poet, and cortegiana honesta Tullia d’Aragona has attracted renewed attention in the past thirty years. In her Dialogo dell’Infinita d’Amore (1547) d’Aragona appeals to intellectual authorities to promote her own ethics of love and affirms her qualifications to insert a female voice into the male-dominated debate. This article explores the social and literary avenues for her access to a vernacular literary tradition which she then leveraged to self-fashion an intellectual identity that garnered the respect of her contemporaries. This analysis of d’Aragona’s invocation of the tre corone (Dante, Boccaccio, and Petrarch) in her Dialogo sheds light on her means of entering the debate on the ethics of love and establishing herself as an authority within this intellectual milieu
Microdrilling Resulted in Less Subchondral Bone Destruction Than a Traditional Microfracture Awl for Articular Cartilage Defect Bone Marrow Stimulation.
No full textPurposeThe purpose of this study was to compare bone marrow stimulation using micro-computed tomography (micro-CT) analysis of an abrasion arthroplasty technique, drilling k-wire technique, traditional microfacture awl, or a microdrill instrument for subchondral bone defects.MethodsEleven cadaveric distal femoral specimens were obtained and divided into 3 common areas of osteochondral defect: trochlea and weightbearing portions of the medial and lateral femoral condyles. Each area of interest was then denuded of cartilage using a PoweRasp and divided into quadrants. Each quadrant was assigned either a 1.6 mm Kirschner wire (k-wire), 1.25 mm microfracture awl, 1.5 mm fluted microdrill, PowerPick, or a curette (abrasion arthroplasty) to create 4 channels into the subchondral bone sing the same instrument. Subchondral bone and adjacent tissue areas were then evaluated using micro-CT to analyze adjacent bone destruction and extension into the bone marrow.ResultsOverall, there was a significantly decreased area of bone destruction or compression using the microdrill (0.030 mm) as compared to the microfracture awl (0.072 mm) and k-wire (0.062 mm) (P P P = .08).ConclusionBone marrow stimulation causes bony compression that may negatively impact subchondral bone and trabecular alignment. It is important to understand which tools used for bone marrow stimulation cause the least amount of damage to the subchondral bone.Clinical relevanceThis study demonstrates the decreased subchondral bony defects seen with the microdrill versus the traditional microfracture awl indicating that when performing bone marrow stimulation, the microdrill may be a less harmful tool to the subchondral bone
5-Hydroxymethylfurfural reduces skeletal muscle superoxide production and modifies force production in rats exposed to hypobaric hypoxia.
No full textDecreased blood-tissue oxygenation at high altitude (HA) increases mitochondrial oxidant production and reduces exercise capacity. 5-Hydroxymethylfurfural (5-HMF) is an antioxidant that increases hemoglobin's binding affinity for oxygen. For these reasons, we hypothesized that 5-HMF would improve muscle performance in rats exposed to a simulated HA of ~5500 m. A secondary objective was to measure mitochondrial activity and dynamic regulation of fission and fusion because they are linked processes impacted by HA. Fisher 344 rats received 5-HMF (40 mg/kg/day) or vehicle during exposure to sea level or HA for 72 h. Right ankle plantarflexor muscle function was measured pre- and post-exposure. Post-exposure measurements included arterial blood gas and complete blood count, flexor digitorum brevis myofiber superoxide production and mitochondrial membrane potential (ΔΨm), and mitochondrial dynamic regulation in the soleus muscle. HA reduced blood oxygenation, increased superoxide levels and lowered ΔΨm, responses that were accompanied by decreased peak isometric torque and force production at frequencies >75 Hz. 5-HMF increased isometric force production and lowered oxidant production at sea level. In HA exposed animals, 5-HMF prevented a decline in isometric force production at 75-125 Hz, prevented an increase in superoxide levels, further decreased ΔΨm, and increased mitochondrial fusion 2 protein expression. These results suggest that 5-HMF may prevent a decrease in hypoxic force production during submaximal isometric contractions by an antioxidant mechanism
Uncommitted State Revolving Funds
No full textStates and the federal government invest in water, wastewater, and stormwater infrastructure by providing subsidized loans and other financial assistance through State Revolving Fund (SRF) programs. The funds are capitalized with federal grants, state contributions, leveraged bonds, and loan repayments. Because the programs largely provide loans rather than grants, the repayment of principal and interest replenishes the pool of capital to finance infrastructure over time. Loan repayments are now the largest source of capital for SRFs. The amount of assistance available through the SRFs will increase substantially as state programs receive $55 billion in new funds through the bipartisan infrastructure law over the next five years.
The increase in available funding—from both federal appropriations and loan repayments—makes it more important than ever for states to efficiently commit funds to finance projects. Uncommitted funds represent missed opportunities to improve public health and water quality, spur economic development, and create jobs through infrastructure investment. As federal funds flow to states faster, it is imperative to understand how states can efficiently allocate funds to reach their full potential. The authors of this report analyzed data from the EPA, interviewed stakeholders, and conducted a survey of over 200 water system decision makers and 30 state SRF administrators to better understand what is driving uncommitted SRF funds.
The report offers three main recommendations to help states allocate funds, described fully in the report:
- Set and track goals for the allocation of funds.
- Stimulate demand for funds.
- Enhance effective administrative practices
Pharmacology of riluzole in acute spinal cord injury.
No full textObjectThe aim of this paper was to characterize individual and population pharmacokinetics of enterally administered riluzole in a Phase 1 clinical trial of riluzole as a neuroprotective agent in adults 18-70 years old with acute spinal cord injury (SCI).MethodsThirty-five individuals with acute SCI, American Spinal Injury Association Impairment Scale Grades A-C, neurological levels from C-4 to T-12, who were enrolled in the Phase 1 clinical trial sponsored by the North American Clinical Trials Network for Treatment of Spinal Cord Injury, received 50 mg riluzole twice daily for 28 doses. The first dose was administered at a mean of 8.7 ± 2.2 hours postinjury. Trough plasma samples were collected within 1 hour predose, and peak plasma samples were collected 2 hours postdose on Days 3 and 14 of treatment. Riluzole concentrations were quantified by high-performance liquid chromatography assay. The data were analyzed for individual and population pharmacokinetics using basic structural and covariate models. The pharmacokinetic measures studied were the peak concentration (C(max)), trough concentration (C(min)), systemic exposure (AUC(0-12)), clearance (CL/F), and volume of distribution (V_F) normalized by the bioavailability (F).ResultsThe C(max) and AUC(0-12) achieved in SCI patients were lower than those in ALS patients on the same dose basis, due to a higher CL and larger V. The pharmacokinetics of riluzole (C(max), C(min), AUC(0-12), CL, and V) changed during the acute and subacute phases of SCI during the 14 days of therapy. It was consistently observed in patients at all clinical sites that C(max), C(min), and AUC(0-12) (128.9 ng/ml, 45.6 ng/ml, and 982.0 ng × hr/ml, respectively) were significantly higher on Day 3 than on Day 14 (76.5 ng/ml, 19.1 ng/ml, and 521.0 ng × hr/ml, respectively). These changes resulted from lower CL (49.5 vs 106.2 L/hour) and smaller V (557.1 vs 1297.9/L) on Day 3. No fluid imbalance or cytochrome P 1A2 induction due to concomitant medications was identified during the treatment course to account for such increases in V and CL, respectively. Possible mechanisms underlying these changes are discussed.ConclusionsThis is the first report of clinical pharmacokinetics of riluzole in patients with SCI. The C(max) and AUC(0-12) achieved in SCI patients were lower than those in ALS patients on the same dose basis, due to a higher clearance and larger volume of distribution in SCI patients. The finding in SCI patients of an increase in the clearance and distribution of riluzole between the 3rd and 14th days after SCI, with a lower plasma concentration of riluzole on the 14th day, stresses the importance of monitoring changes in drug metabolism after SCI in interpreting the safety and efficacy of therapeutic drugs that are used in clinical trials in SCI. Clinical trial registration no.: NCT00876889
Potential of predictive computer models for preoperative patient selection to enhance overall quality-adjusted life years gained at 2-year follow-up: a simulation in 234 patients with adult spinal deformity.
No full textOBJECTIVE Patients with adult spinal deformity (ASD) experience significant quality of life improvements after surgery. Treatment, however, is expensive and complication rates are high. Predictive analytics has the potential to use many variables to make accurate predictions in large data sets. A validated minimum clinically important difference (MCID) model has the potential to assist in patient selection, thereby improving outcomes and, potentially, cost-effectiveness. METHODS The present study was a retrospective analysis of a multiinstitutional database of patients with ASD. Inclusion criteria were as follows: age ≥ 18 years, radiographic evidence of ASD, 2-year follow-up, and preoperative Oswestry Disability Index (ODI) > 15. Forty-six variables were used for model training: demographic data, radiographic parameters, surgical variables, and results on the health-related quality of life questionnaire. Patients were grouped as reaching a 2-year ODI MCID (+MCID) or not (-MCID). An ensemble of 5 different bootstrapped decision trees was constructed using the C5.0 algorithm. Internal validation was performed via 70:30 data split for training/testing. Model accuracy and area under the curve (AUC) were calculated. The mean quality-adjusted life years (QALYs) and QALYs gained at 2 years were calculated and discounted at 3.5% per year. The QALYs were compared between patients in the +MCID and -MCID groups. RESULTS A total of 234 patients met inclusion criteria (+MCID 129, -MCID 105). Sixty-nine patients (29.5%) were included for model testing. Predicted versus actual results were 50 versus 40 for +MCID and 19 versus 29 for -MCID (i.e., 10 patients were misclassified). Model accuracy was 85.5%, with 0.96 AUC. Predicted results showed that patients in the +MCID group had significantly greater 2-year mean QALYs (p = 0.0057) and QALYs gained (p = 0.0002). CONCLUSIONS A successful model with 85.5% accuracy and 0.96 AUC was constructed to predict which patients would reach ODI MCID. The patients in the +MCID group had significantly higher mean 2-year QALYs and QALYs gained. This study provides proof of concept for using predictive modeling techniques to optimize patient selection in complex spine surgery
Designing and Implementing a Community-Engaged Research e-Library: A Case Study for Adapting Academic Library Information Infrastructure to Respond to Stakeholder Needs
No full textRisk for opioid abuse is diminished by inhibiting aldehyde dehydrogenase-2 (ALDH-2) in rats
No full textSignificant opiate addiction is known to follow prescribed opiate use for pain. There is a serious unmet need for non-addicting medications to prevent subsequent opiate addiction after a short period of opioid treatment for temporary pain. Recent evidence indicates that selective inhibition of aldehyde dehydrogenase-2 (ALDH-2) reduces drug-seeking and trained self-administration of alcohol, cocaine and nicotine, apparently by preventing a concomitant surge of dopamine in the ventral tegmental area (VTA) and nucleus accumbens (NAc). Activation of the same dopaminergic pathway is also implicated in opioid-induced reinforcement. Therefore, we asked whether the selective ALDH-2 inhibitor, ANS-6637, would attenuate opioid self-administration in drug-naïve rats for opioid self-administration. Rats received oral doses of ANS-6637 (9, 18, 36 or 72 mg/kg) or an equal volume of control vehicle 2 h before exposure to remifentanil and a light cue to accentuate self-administration over 5 consecutive days. Self-administration and the numbers of lever presses on both active and inactive levers were recorded. ANS-6637 significantly reduces remifentanil self-administration over 5 sessions of treatment in rats without prior exposure to remifentanil. We also confirm that the highest dose of ANS-6637 (72 mg/kg) used in this study did not prevent remifentanil-induced analgesia using a classic hot plate test. Thus, ANS-6637 significantly reduces of initial exposure to remifentanil self-administration without affecting desired analgesia. These preliminary observations suggest that ANS-6637 appears to have potential value as a non-addictive therapeutic agent to prevent abuse of commonly used opiates in initiating pain management