Dexterity test data contribute to reduction in leaded glovebox gloves use

Programmatic operations at the Los Alamos National Laboratory Plutonium Facility (T A-55) involve working with various amounts of plutonium and other highly toxic, alpha-emitting materials. The spread of radiological contamination on surfaces, airborne contamination, and excursions of contaminants into the operator's breathing zone are prevented through the use of a variety of gloveboxes. Using an integrated approach, controls have been developed and implemented through an efficient Glovebox Glove Integrity Program. A key element of this program is to consider measures that lower the overall risk of glovebox operations. Line management who own glovebox processes through this program make decisions on which type of glovebox gloves (hereafter referred to as gloves), the weakest component of this safety-significant system, would perform best in these aggressive environments. As Low as Reasonably Achievable considerations must be balanced with glove durability and worker dexterity, both of which affect the final overall risk of the operation. In the past, lead-loaded (leaded) gloves made from Hypalon(reg.) were the primary glove for programmatic operations at TA55. Replacing leaded gloves with unleaded gloves for certain operations would lower the overall risk as well as reduce the amount of mixed transuranic waste. This effort contributes to the Los Alamos National Laboratory Continuous Improvement Program by improving the efficiency, cost-effectiveness, and formality of glovebox operations. In this report, the pros and cons of wearing leaded gloves, the effect of leaded gloves versus unleaded gloves on task performance using standard dexterity tests, the justification for switching from leaded to unleaded gloves, and the pollution prevention benefits of this dramatic change in the glovebox system are presented

Early-Stage Metastasis Requires Mdm2 and Not p53 Gain of Function

Metastasis of cancer cells to distant organ systems is a complex process that is initiated with the programming of cells in the primary tumor. The formation of distant metastatic foci is correlated with poor prognosis and limited effective treatment options. We and others have correlated Mouse double minute 2 (Mdm2) with metastasis; however, the mechanisms involved have not been elucidated. Here, it is reported that shRNA-mediated silencing of Mdm2 inhibits epithelial–mesenchymal transition (EMT) and cell migration. In vivo analysis demonstrates that silencing Mdm2 in both post-EMT and basal/triple-negative breast cancers resulted in decreased primary tumor vasculature, circulating tumor cells, and metastatic lung foci. Combined, these results demonstrate the importance of Mdm2 in orchestrating the initial stages of migration and metastasis

Micromechanical Properties of Injection-Molded Starch–Wood Particle Composites

The micromechanical properties of injection molded starch–wood particle composites were investigated as a function of particle content and humidity conditions. The composite materials were characterized by scanning electron microscopy and X-ray diffraction methods. The microhardness of the composites was shown to increase notably with the concentration of the wood particles. In addition,creep behavior under the indenter and temperature dependence were evaluated in terms of the independent contribution of the starch matrix and the wood microparticles to the hardness value. The influence of drying time on the density and weight uptake of the injection-molded composites was highlighted. The results revealed the role of the mechanism of water evaporation, showing that the dependence of water uptake and temperature was greater for the starch–wood composites than for the pure starch sample. Experiments performed during the drying process at 70°C indicated that the wood in the starch composites did not prevent water loss from the samples.Peer reviewe

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Software programs that address site-specific inventory characteristics issues.

The proper characterization of Hazardous, Mixed Low-Level, and Mixed Transuranic waste enhances productivity and safety. Hazardous material criteria that need to be considered include physical and health hazards inherent to the waste stream. Other factors that may influence characterization include: particulate diameter, complexing or chelating agent properties, lead, and mercury content, pressurized containers, and P-listed wastes. To meet these requirements are only a simple matter of generating a database with the proper fields. Manufactures and institutional databases bank huge sources of information, such as, work control documents, substance identification, container types, components of mixtures, physical property data, and regulatory data. In this report, utilization of commercially available software programs to take advantage of these resources in addressing waste characterization issues are presented. The application of user-friendly programs eliminates part of the tediousness associated with the complex requirements of certifying to general waste acceptance criteria with minimal impact on programmatic work. In other words, tapping into manufacturer and institutional database provides a way to take advantage of the combined expertise of these resources in managing a cost effective waste certification program as well as adding a quality assurance element to the program

Waste Issues Associated with the Safe Movement of Hazardous Chemicals

Moving hazardous chemicals presents the risk of exposure for workers engaged in the activity and others that might be in the immediate area. Adverse affects are specific to the chemicals and can range from minor skin, eye, or mucous membrane irritation, to burns, respiratory distress, nervous system dysfunction, or even death. A case study is presented where in the interest of waste minimization; original shipping packaging was removed from a glass bottle of nitric acid, while moving corrosive liquid through a security protocol into a Radiological Control Area (RCA). During the transfer, the glass bottle broke. The resulting release of nitric acid possibly exposed 12 employees with one employee being admitted overnight at a hospital for observation. This is a clear example of administrative controls to reduce the generation of suspect radioactive waste being implemented at the expense of employee health. As a result of this event, material handling procedures that assure the safe movement of hazardous chemicals through a security protocol into a radiological control area were developed. Specifically, hazardous material must be transferred using original shipping containers and packaging. While this represents the potential to increase the generation of suspect radioactive waste in a radiological controlled area, arguments are presented that justify this change. Security protocols for accidental releases are also discussed. In summary, the 12th rule of ''Green Chemistry'' (Inherently Safer Chemistry for Accident Prevention) should be followed: the form of a substance used in a chemical process (Movement of Hazardous Chemicals) should be chosen to minimize the potential for chemical accidents, including releases

Determining risks for hazardous material operations

Integrated Safety Management (ISM) is structured to manage and control work at the activity level. Fundamental to ISM is that all work will be performed safely while meeting the applicable institutional-, facility-, and activity-level expectations. High and medium initial risk activities require certain levels of independent peer and/or Environmental, Health & Safety subject matter expert reviews prior to authorization. A key responsibility of line management and chemical workers is to assign initial risk adequately, so that the proper reviews are obtained. Thus, the effectiveness of an ISM system is largely dependent upon the adequacy and accuracy of this initial risk determination. In the following presentation, a Risk Determination Model (RDM) is presented for physical, health and ecological hazards associated with materials. Magnitude of exposure (Le., dose or concentration), frequency, duration, and quantity are the four factors most difficult to capture in a research and development setting. They are factored into the determination, as a function of the quantity of material. Quantity and magnitude of exposure components are simplified by using boundary criteria. This RDM will promote conformity and consistency in the assignment of risk to hazardous material activities. In conclusion, the risk assessors (line manager and chemical worker) should be capable of more accurately assessing the risk of exposure to a specific chemical with regard to the employee, public, and the environment

ADDRESSING POLLUTION PREVENTION ISSUES IN THE DESIGN OF A NEW NUCLEAR RESEARCH FACILITY

The Chemistry and Metallurgical Research (CMR) Facility was designed in 1949 and built in 1952 at Los Alamos National Laboratory (LANL) to support analytical chemistry, metallurgical studies, and actinide research and development on samples of plutonium and other nuclear materials for the Atomic Energy Commission's nuclear weapons program. These primary programmatic uses of the CMR Facility have not changed significantly since it was constructed. In 1998, a seismic fault was found to the west of the CMR Facility and projected to extend beneath two wings of the building. As part of the overall Risk Management Strategy for the CMR Facility, the Department of Energy (DOE) proposed to replace it by 2010 with what is called the CMR Facility Replacement (CMRR). In an effort to make this proposed new nuclear research facility environmentally sustainable, several pollution prevention/waste minimization initiatives are being reviewed for potential incorporation during the design phase. A two-phase approach is being adopted; the facility is being designed in a manner that integrates pollution prevention efforts, and programmatic activities are being tailored to minimize waste. Processes and procedures that reduce waste generation compared to current, prevalent processes and procedures are identified. Some of these ''best practices'' include the following: (1) recycling opportunities for spent materials; (2) replacing lithium batteries with alternate current adaptors; (3) using launderable contamination barriers in Radiological Control Areas (RCAs); (4) substituting mercury thermometers and manometers in RCAs with mercury-free devices; (5) puncturing and recycling aerosol cans; (6) using non-hazardous low-mercury fluorescent bulbs where available; (7) characterizing low-level waste as it is being generated; and (8) utilizing lead alternatives for radiological shielding. Each of these pollution prevention initiatives are being assessed for their technical validity, relevancy, and cost effectiveness. These efforts partially fulfill expectations of the DOE, other federal agencies, and the State of New Mexico for waste minimization. If the improvements discussed here are implemented, an estimated 1.8 million dollars in cost savings is expected

Dexterity tests data contribute to reduction in leaded glovebox gloves use

Programmatic operations at the Los Alamos National Laboratory Plutonium Facility (TA-55) involve working with various amounts of plutonium and other highly toxic, alphaemitting materials. The spread of radiological contamination on surfaces and airborne contamination and excursions of contaminants into the operator's breathing zone are prevented through the use of a variety of gloveboxes. Through an integrated approach, controls have been developed and implemented through an efficient Glovebox Glove Integrity Program (GGJP). A key element of this program is to consider measures that lower the overall risk of glovebox operations. Line management owning glovebox processes through this program make decisions on which type of glovebox gloves (the weakest component of this safety significant system) would perform in these aggressive environments. As Low As Reasonably Achievable (ALARA) considerations must be balanced with glove durability and worker dexterity, both of which affect the final overall risk of the operation. In the past, lead-loaded (leaded) glovebox gloves made from Hypalon(reg.) had been the workhorse of programmatic operations at TA-55. Replacing leaded gloves with unleaded gloves for certain operations would lower the overall risk as well as reduced the amount of mixed TRU waste. This effort contributes to Los Alamos National Laboratory Continuous Improvement Program by improving the efficiency, cost effectiveness, and formality of glovebox operations. In the following report, the pros and cons of wearing leaded glovebox gloves, the effect of leaded gloves versus unleaded gloves on task performance using standard dexterity tests, the justification for switching from leaded to unleaded gloves, and pollution prevention benefits of this dramatic change in the glovebox system are presented