ABSTRACT
Despite longstanding excitement and progress toward understanding liquid-liquid phase separation in natural and artificial membranes, fundamental questions have persisted about which molecules are required for this phenomenon. Except in extraordinary circumstances, the smallest number of components that has produced large-scale, liquid-liquid phase separation in bilayers has stubbornly remained at three: a sterol, a phospholipid with ordered chains, and a phospholipid with disordered chains. This requirement of three components is puzzling for two reasons: (1) the Gibbs Phase Rule states that only two components are necessary, and (2) only two components are required for liquid-liquid phase separation in lipid monolayers, which resemble half of a bilayer. Inspired by reports that sterols interact closely with lipids with ordered chains, we tested whether phase separation would occur in bilayers in which a sterol and lipid were replaced by a single, joined sterol-lipid. By evaluating a panel of sterol-lipids, we discovered a minimal bilayer of only two components (PChemsPC and diPhyPC) that demixes into micron-scale, liquid phases. In this system, the sterol-lipid behaves as a 3:1 ratio of cholesterol to phospholipid. Our system gives the computation and theory community a two-component membrane that maps directly onto simplified theories and that can be used to validate simulation force fields. It suggests a new role for sterol-lipids in nature, and it gives experimental communities a membrane in which tie-lines (and, therefore, the lipid composition of each phase) are easily determined and will be consistent across multiple laboratories. Significance Statement: A wide diversity of bilayer membranes, from those with hundreds of lipids (e.g., vacuoles of living yeast cells) to those with very few (e.g., artificial vesicles) phase separate into micron-scale liquid domains. The number of components required for liquid-liquid phase separation has been perplexing: only two should be necessary, but more are required except in extraordinary circumstances. What minimal set of molecular characteristics leads to liquid-liquid phase separation in bilayer membranes? This question inspired us to search for single, joined "sterol-lipid" molecules to replace both a sterol and a phospholipid in membranes undergoing liquid-liquid phase separation. By producing phase-separating membranes with only two components, we mitigate experimental challenges in determining tie-lines and in maintaining constant chemical potentials of lipids.
ABSTRACT
Background: Mechanical thrombectomy (MT) can improve the outcomes of patients with large vessel occlusion (LVO), but a minority of patients with LVO are treated and there are disparities in timely access to MT. In part, this is because in most regions, including Alabama, the emergency medical service (EMS) transports all patients with suspected stroke, regardless of severity, to the nearest stroke center. Consequently, patients with LVO may experience delayed arrival at stroke centers with MT capability and worse outcomes. Alabama's trauma communications center (TCC) coordinates EMS transport of trauma patients by trauma severity and regional hospital capability. Our aims are to develop a severity-based stroke triage (SBST) care model based on Alabama's trauma system, compare the effectiveness of this care pathway to current stroke triage in Alabama for improving broad, equitable, and timely access to MT, and explore stakeholder perceptions of the intervention's feasibility, appropriateness, and acceptability. Methods: This is a hybrid type 1 effectiveness-implementation study with a multi-phase mixed methods sequential design and an embedded observational stepped wedge cluster trial. We will extend TCC guided stroke severity assessment to all EMS regions in Alabama; conduct stakeholder interviews and focus groups to aid in development of region and hospital specific prehospital and inter-facility stroke triage plans for patients with suspected LVO; implement a phased rollout of TCC Coordinated SBST across Alabama's six EMS regions; and conduct stakeholder surveys and interviews to assess context-specific perceptions of the intervention. The primary outcome is the change in proportion of prehospital stroke system patients with suspected LVO who are treated with MT before and after implementation of TCC Coordinated SBST. Secondary outcomes include change in broad public health impact before and after implementation and stakeholder perceptions of the intervention's feasibility, appropriateness, and acceptability using a mixed methods approach. With 1200 to 1300 total observations over 36 months, we have 80% power to detect a 15% improvement in the primary endpoint. Discussion: This project, if successful, can demonstrate how the trauma system infrastructure can serve as the basis for a more integrated and effective system of emergency stroke care.
ABSTRACT
Advance care planning (ACP) increases the likelihood that individuals who are dying receive the care that they prefer. It also reduces depression and anxiety in family members and increases family satisfaction with the process of care. Honoring Choices Minnesota is an ACP program based on the Respecting Choices model of La Crosse, Wisconsin. The objective of this report is to describe the process, which began in 2008, of implementing Honoring Choices Minnesota in a large, diverse metropolitan area. All eight large healthcare systems in the metropolitan area agreed to participate in the project, and as of April 30, 2013, the proportion of hospitalized individuals 65 and older with advance care directives in the electronic medical record was 12.1% to 65.6%. The proportion of outpatients aged 65 and older was 11.6% to 31.7%. Organizations that had sponsored recruitment initiatives had the highest proportions of records containing healthcare directives. It was concluded that it is possible to reduce redundancy by recruiting all healthcare systems in a metropolitan area to endorse the same ACP model, although significantly increasing the proportion of individuals with a healthcare directive in their medical record requires a campaign with recruitment of organizations and individuals.
Subject(s)
Advance Care Planning/organization & administration , Community Health Services/organization & administration , Aged , Decision Making , Female , Focus Groups , Humans , Male , Minnesota , Models, Organizational , Program Development , Program EvaluationABSTRACT
Beryllium has been historically machined, handled and stored in facilities at Lawrence Livermore National Laboratory (LLNL) since the 1950s. Additionally, outdoor testing of beryllium-containing components has been performed at LLNL's Site 300 facility. Beryllium levels in local soils and atmospheric particulates have been measured over three decades and are comparable to those found elsewhere in the natural environment. While localized areas of beryllium contamination have been identified, laboratory operations do not appear to have increased the concentration of beryllium in local air or water. Variation in airborne beryllium correlates to local weather patterns, PM10 levels, normal sources (such as resuspension of soil and emissions from coal power stations) but not to LLNL activities. Regional and national atmospheric beryllium levels have decreased since the implementation of the EPA's 1990 Clean-Air-Act. Multi-element analysis of local soil and air samples allowed for the determination of comparative ratios for beryllium with over 50 other metals to distinguish between natural beryllium and process-induced contamination. Ten comparative elemental markers (Al, Cs, Eu, Gd, La, Nd, Pr, Sm, Th and Tl) that were selected to ensure background variations in other metals did not collectively interfere with the determination of beryllium sources in work-place samples at LLNL. Multi-element analysis and comparative evaluation are recommended for all workplace and environmental samples suspected of beryllium contamination. The multi-element analyses of soils and surface dusts were helpful in differentiating between beryllium of environmental origin and beryllium from laboratory operations. Some surfaces can act as "sinks" for particulate matter, including carpet, which retains entrained insoluble material even after liquid based cleaning. At LLNL, most facility carpets had beryllium concentrations at or below the upper tolerance limit determined by sampling facilities with no history of beryllium work. Some facility carpets had beryllium concentrations above the upper tolerance limits but can be attributed to tracking of local soils, while other facilities showed process-induced contamination from adjacent operations. In selected cases, distinctions were made as to the source of beryllium in carpets. Guidance on the determination of facility beryllium sources is given.
