Reengineering RCRA: The Command Control Requirements of the Waste Disposal Paradigm of Subtitle C and the Act’s Objective of Fostering Recycling-Rethinking the Definition of Solid Waste, Again

INTRODUCTION In 1992, the United States Environmental Protection Agency (EPA) created the Definition of Solid Waste Task Force (Task Force). 1 Specifically, the Task Force was created to eliminate perceived disincentives to recycling, eliminate regulatory loopholes for those recycling practices presenting risks to health and the environment, and clarify the definition of solid waste. 2 In September, 1994, the Task Force published a report titled Reengineering RCRA for Recycling: Definition of Solid Waste Task Force: Report and Recommendations (Reengineering RCRA). 3 This report advocated a new national regulatory system for recycling. 4 Consistent with past practice, the proposed system is to be administered by the EPA through jurisdiction vested in it by the Resource Conservation and Recovery Act of 1976 (RCRA), 5 as amended by the Hazardous and Solid Waste Amendments of 1984 (HSWA) 6 . 7 The development of a regulatory system for the recycling of industrial, commercial, and municipal solid wastes is currently among the most significant issues in the environmental policy arena. 8 While the development of other solid waste policies (such as the shift to producer responsibility and the development of market forces to encourage waste reduction and reuse) are increasingly being addressed on a global scale, RCRA recycling is a distinctly national issue. 9 The focus of this article is to develop a regulatory framework for a new national recycling system. The discussion contained herein advocates a regulatory system that moves away from perceptions of recycling as a subset of ..

Long-Term Safety of a Novel Antianginal Agent in Patients With Severe Chronic Stable Angina The Ranolazine Open Label Experience (ROLE)

ObjectivesThis report describes safety and tolerability data from 746 chronic angina patients treated in the ROLE (Ranolazine Open Label Experience) program.BackgroundRanolazine treats angina without depressing hemodynamic status. The long-term safety and tolerability of ranolazine have not been previously reported.MethodsPatients with severe functional impairment from angina (mean Duke Treadmill Score [DTS] of −14.4) who completed 1 of 2 randomized treadmill trials entered the ROLE program. Ranolazine was titrated to optimal dosages between 500 and 1,000 mg twice daily. Physical examination, laboratory tests, and adverse event reporting were performed periodically. We conducted analyses to evaluate possible predictors of ranolazine intolerance, such as advanced age, diabetes, poor exercise tolerance, or history of myocardial infarctions or congestive heart failure (CHF). The ROLE program’s mortality was compared against the DTS predictive model and other contemporary cohorts of high-risk CHD patients.ResultsMean follow-up was 2.82 years. Two years after initial dosing, 571 patients (76.7%) remained on therapy and 72 patients (9.7%) discontinued ranolazine due to adverse events. Among 6 factors evaluated, only age ≥64 years predicted for higher withdrawal rates. Patients with a history of CHF had lower withdrawal rates. Mean QTc interval was prolonged by 2.4 ms. No treatment discontinuations occurred due to QTc prolongation, and no Torsades de Pointes was reported. Sixty-four deaths occurred during a total of 2,102 patient-years (3.0% annually) during the ROLE program. When extending observations to all patients exposed to ranolazine during the double-blind trials (n = 972) preceding the ROLE program, annual mortality was 2.8% compared with >5% as predicted by DTS.ConclusionsLong-term therapy with ranolazine seems well tolerated in high-risk CHD patients. Survival analyses suggest that symptomatic improvements attributable to ranolazine are not offset by increased mortality

A Case of Unintentional Isopropanol Poisoning via Transdermal Absorption Delayed by Weekly Hemodialysis

BACKGROUND Isopropanol toxicity is the most common reported toxic alcohol ingestion in the United States and is well known to emergency physicians. Most toxicities result from unintentional ingestion of rubbing alcohol; however, an under-recognized mechanism of unintentional toxicity is transdermal absorption. Additionally, hemodialysis effectively removes isopropanol and its metabolites from circulation, so that in patients receiving regular hemodialysis, the manifestation of toxicity can be delayed. CASE REPORT A 67-year-old woman with end-stage renal disease secondary to insulin-dependent type II diabetes on once-weekly hemodialysis presented to the Emergency Department via the Emergency Medical Service with acute encephalopathy, severe hypoglycemia, and hypothermia. Her daughter found her confused and lethargic, smelling of acetone, and with a bottle of rubbing alcohol in her hand. The patient had been topically applying large quantities of rubbing alcohol for several months as a home remedy for cramps and adamantly denied any oral ingestion. She had missed several hemodialysis appointments over the previous month. Upon arrival, the patient was confused, profoundly hypoglycemic, and hypothermic. Additional laboratory examination revealed an elevated plasma osmolality, osmolar gap, isopropanol level, and acetone level. She was treated supportively with glucose-containing fluids and external warming and was admitted to the Intensive Care Unit. Hemodialysis was resumed, and the patient was discharged 3 days after admission with stable blood glucose, regular body temperature, and baseline mental status. CONCLUSIONS Our report is unique as it presents both an under-recognized mechanism of isopropanol toxicity (transdermal absorption) and an uncommon presentation of chronic exposure with manifestations of toxicity delayed by regular hemodialysis

Serendipitous Discovery of Light-Induced \u3cem\u3e(In Situ)\u3c/em\u3e Formation of An Azo-Bridged Dimeric Sulfonated Naphthol as a Potent PTP1B Inhibito

Background Protein tyrosine phosphatases (PTPs) like dual specificity phosphatase 5 (DUSP5) and protein tyrosine phosphatase 1B (PTP1B) are drug targets for diseases that include cancer, diabetes, and vascular disorders such as hemangiomas. The PTPs are also known to be notoriously difficult targets for designing inihibitors that become viable drug leads. Therefore, the pipeline for approved drugs in this class is minimal. Furthermore, drug screening for targets like PTPs often produce false positive and false negative results. Results Studies presented herein provide important insights into: (a) how to detect such artifacts, (b) the importance of compound re-synthesis and verification, and (c) how in situ chemical reactivity of compounds, when diagnosed and characterized, can actually lead to serendipitous discovery of valuable new lead molecules. Initial docking of compounds from the National Cancer Institute (NCI), followed by experimental testing in enzyme inhibition assays, identified an inhibitor of DUSP5. Subsequent control experiments revealed that this compound demonstrated time-dependent inhibition, and also a time-dependent change in color of the inhibitor that correlated with potency of inhibition. In addition, the compound activity varied depending on vendor source. We hypothesized, and then confirmed by synthesis of the compound, that the actual inhibitor of DUSP5 was a dimeric form of the original inhibitor compound, formed upon exposure to light and oxygen. This compound has an IC50 of 36 μM for DUSP5, and is a competitive inhibitor. Testing against PTP1B, for selectivity, demonstrated the dimeric compound was actually a more potent inhibitor of PTP1B, with an IC50 of 2.1 μM. The compound, an azo-bridged dimer of sulfonated naphthol rings, resembles previously reported PTP inhibitors, but with 18-fold selectivity for PTP1B versus DUSP5. Conclusion We report the identification of a potent PTP1B inhibitor that was initially identified in a screen for DUSP5, implying common mechanism of inhibitory action for these scaffolds

Four new T dwarfs identified in PanSTARRS 1 commissioning data

A complete well-defined sample of ultracool dwarfs is one of the key science programs of the Pan-STARRS 1 optical survey telescope (PS1). Here we combine PS1 commissioning data with 2MASS to conduct a proper motion search (0.1--2.0\arcsec/yr) for nearby T dwarfs, using optical+near-IR colors to select objects for spectroscopic followup. The addition of sensitive far-red optical imaging from PS1 enables discovery of nearby ultracool dwarfs that cannot be identified from 2MASS data alone. We have searched 3700 sq. deg. of PS1 y-band (0.95--1.03 um) data to y$\approx$19.5 mag (AB) and J$\approx$16.5 mag (Vega) and discovered four previously unknown bright T dwarfs. Three of the objects (with spectral types T1.5, T2 and T3.5) have photometric distances within 25 pc and were missed by previous 2MASS searches due to more restrictive color selection criteria. The fourth object (spectral type T4.5) is more distant than 25 pc and is only a single-band detection in 2MASS. We also examine the potential for completing the census of nearby ultracool objects with the PS1 3$\pi$ survey.Comment: 25 pages, 8 figures, 5 table, AJ accepted, updated to comply with Pan-STARRS1 naming conventio

On Bayesian Modelling of the Uncertainties in Palaeoclimate Reconstruction

We outline a model and algorithm to perform inference on the palaeoclimate and palaeoclimate volatility from pollen proxy data. We use a novel multivariate non-linear non-Gaussian state space model consisting of an observation equation linking climate to proxy data and an evolution equation driving climate change over time. The link from climate to proxy data is defined by a pre-calibrated forward model, as developed in Salter-Townshend and Haslett (2012) and Sweeney (2012). Climatic change is represented by a temporally-uncertain Normal-Inverse Gaussian Levy process, being able to capture large jumps in multivariate climate whilst remaining temporally consistent. The pre-calibrated nature of the forward model allows us to cut feedback between the observation and evolution equations and thus integrate out the state variable entirely whilst making minimal simplifying assumptions. A key part of this approach is the creation of mixtures of marginal data posteriors representing the information obtained about climate from each individual time point. Our approach allows for an extremely efficient MCMC algorithm, which we demonstrate with a pollen core from Sluggan Bog, County Antrim, Northern Ireland.Comment: 25 pages, 7 figure

Metastatic meningioma: positron emission tomography CT imaging findings

The imaging findings of a case of metastasing meningioma are described. The case illustrates a number of rare and interesting features. The patient presented with haemoptysis 22 years after the initial resection of an intracranial meningioma. CT demonstrated heterogeneous masses with avid peripheral enhancement without central enhancement. Blood supply to the larger lesion was partially from small feeding vessels from the inferior pulmonary vein. These findings correlate with a previously published case in which there was avid uptake of fluoro-18-deoxyglucose peripherally with lesser uptake centrally. The diagnosis of metastasing meningioma was confirmed on percutaneous lung tissue biopsy

Metastatic meningioma: positron emission tomography CT imaging findings

The imaging findings of a case of metastasing meningioma are described. The case illustrates a number of rare and interesting features. The patient presented with haemoptysis 22 years after the initial resection of an intracranial meningioma. CT demonstrated heterogeneous masses with avid peripheral enhancement without central enhancement. Blood supply to the larger lesion was partially from small feeding vessels from the inferior pulmonary vein. These findings correlate with a previously published case in which there was avid uptake of fluoro-18-deoxyglucose peripherally with lesser uptake centrally. The diagnosis of metastasing meningioma was confirmed on percutaneous lung tissue biopsy

Essential role of syntaxin-binding protein-1 in the regulation of glucagon-like peptide-1 secretion

Circadian secretion of the incretin, glucagon-like peptide-1 (GLP-1), correlates with expression of the core clock gene, Bmal1, in the intestinal L-cell. Several SNARE proteins known to be circadian in pancreatic α- and β-cells are also necessary for GLP-1 secretion. However, the role of the accessory SNARE, Syntaxin binding protein-1 (Stxbp1; also known as Munc18-1) in the L-cell is unknown. The aim of this study was to determine whether Stxbp1 is under circadian regulation in the L-cell and its role in the control of GLP-1 secretion. Stxbp1 was highly-enriched in L-cells, and STXBP1 was expressed in a subpopulation of L-cells in mouse and human intestinal sections. Stxbp1 transcripts and protein displayed circadian patterns in mGLUTag L-cells line, while chromatin-immunoprecipitation revealed increased interaction between BMAL1 and Stxbp1 at the peak time-point of the circadian pattern. STXBP1 recruitment to the cytosol and plasma membrane within 30 minutes of L-cell stimulation was also observed at this time-point. Loss of Stxbp1 in vitro and in vivo led to reduced stimulated GLP-1 secretion at the peak time-point of circadian release, and impaired GLP-1 secretion ex vivo. In conclusion, Stxbp1 is a circadian regulated exocytotic protein in the intestinal L-cell that is an essential regulatory component of GLP-1 secretion.Wellcome Trust MR

Multi-device study of temporal characteristics of magnetohydrodynamic modes initiating disruptions

Disruptions in tokamaks are often preceded by magnetohydrodynamic (MHD) instabilities that can rotate or become locked to the wall. Measurements from magnetic diagnostics in the presence of MHD mode precursors to disruptions can yield potentially valuable input to the plasma control system, with a view to disruption avoidance, prediction and mitigation. This paper presents an exploratory analysis of the growth of MHD modes and corresponding time scales on the basis of magnetic measurements in multiple tokamaks. To this end, a database was compiled using disruptive discharges from COMPASS, ASDEX Upgrade, DIII-D and JET, manually classified according to disruption root cause, and characterized by a great diversity of operational conditions and mode dynamics. The typical time during which a mode can be detected using saddle coils and the duration of the locked mode phase in the database both extend over several orders of magnitude, but generally the time scales increase with plasma size. Several additional factors are discussed that can influence these durations, including the disruption root cause. A scaling law for the locked phase duration was estimated, yielding predictions toward ITER of the order of hundreds of milliseconds or even seconds. In addition, a scaling law for the mode amplitude at the disruption onset, proposed earlier by de Vries et al. (2016), is applied to the database, and its predictive capabilities are assessed. Despite significant uncertainty on the predictions from both scaling laws, encouraging trends are observed of the fraction of disruptions that may be detected with sufficient warning time to allow mitigation or even avoidance, based solely on observations of MHD mode dynamics. When combined with similar analysis of measurements from diagnostics that are sensitive to other disruption precursors, our analysis methods and results may contribute to the reliability, robustness and generalization of disruption warning schemes for ITER