High-resolution single-particle imaging at 100-200 keV with the Gatan Alpine direct electron detector.

Developments in direct electron detector technology have played a pivotal role in enabling high-resolution structural studies by cryo-EM at 200 and 300 keV. Yet, theory and recent experiments indicate advantages to imaging at 100 keV, energies for which the current detectors have not been optimized. In this study, we evaluated the Gatan Alpine detector, designed for operation at 100 and 200 keV. Compared to the Gatan K3, Alpine demonstrated a significant DQE improvement at these energies, specifically a âˆ¼ 4-fold improvement at Nyquist at 100 keV. In single-particle cryo-EM experiments, Alpine datasets yielded better than 2 Å resolution reconstructions of apoferritin at 120 and 200 keV on a ThermoFisher Scientific (TFS) Glacios microscope fitted with a non-standard SP-Twin lens. We also achieved a âˆ¼ 3.2 Å resolution reconstruction of a 115 kDa asymmetric protein complex, proving Alpine's effectiveness with complex biological samples. In-depth analysis revealed that Alpine reconstructions are comparable to K3 reconstructions at 200 keV, and remarkably, reconstruction from Alpine at 120 keV on a TFS Glacios surpassed all but the 300 keV data from a TFS Titan Krios with GIF/K3. Additionally, we show Alpine's capability for high-resolution data acquisition and screening on lower-end systems by obtaining âˆ¼ 3 Å resolution reconstructions of apoferritin and aldolase at 100 keV and detailed 2D averages of a 55 kDa sample using a side-entry cryo holder. Overall, we show that Gatan Alpine performs well with the standard 200 keV imaging systems and may potentially capture the benefits of lower accelerating voltages, bringing smaller sized particles within the scope of cryo-EM.

Clustered and distinct: a taxonomy of local multihospital systems.

Despite their prevalence and power in markets throughout the United States, local multihospital systems (LMSs)-also referred to as hospital-based "clusters"-remain an understudied organizational form, with studies instead primarily focusing either upon individual hospitals or viewing hospital systems collectively without distinguishing the local "sub-systems" that comprise larger regional or national hospital chains. To better understand these organizational forms, we develop a taxonomy specifically devoted to LMSs, applying taxonomic analysis methods to a sample of LMSs in six U.S. states while accounting for LMSs' geographic arrangements and non-hospital-based service locations. Our analysis identifies five distinct LMS categories, with forms clearly distinguished according to their varying degrees of differentiation and integration. The study's results accentuate the importance of accounting for hospital systems' activities and arrangements in local markets-including their non-hospital-based sites-and highlight differences in systems' achievement of integration and coordination across services and locations, providing considerations in light of U.S. health system reform as well as international patterns of regional system formation.

Atomic resolution scanning transmission electron microscopy at liquid helium temperatures for quantum materials.

Fundamental quantum phenomena in condensed matter, ranging from correlated electron systems to quantum information processors, manifest their emergent characteristics and behaviors predominantly at low temperatures. This necessitates the use of liquid helium (LHe) cooling for experimental observation. Atomic resolution scanning transmission electron microscopy combined with LHe cooling (cryo-STEM) provides a powerful characterization technique to probe local atomic structural modulations and their coupling with charge, spin and orbital degrees-of-freedom in quantum materials. However, achieving atomic resolution in cryo-STEM is exceptionally challenging, primarily due to sample drifts arising from temperature changes and noises associated with LHe bubbling, turbulent gas flow, etc. In this work, we demonstrate atomic resolution cryo-STEM imaging at LHe temperatures using a commercial side-entry LHe cooling holder. Firstly, we examine STEM imaging performance as a function of He gas flow rate, identifying two primary noise sources: He-gas pulsing and He-gas bubbling. Secondly, we propose two strategies to achieve low noise conditions for atomic resolution STEM imaging: either by temporarily suppressing He gas flow rate using the needle valve or by acquiring images during the natural warming process. Lastly, we show the applications of image acquisition methods and image processing techniques in investigating structural phase transitions in Cr2Ge2Te6, CuIr2S4, and CrCl3. Our findings represent an advance in the field of atomic resolution electron microscopy imaging for quantum materials and devices at LHe temperatures, which can be applied to other commercial side-entry LHe cooling TEM holders.

High-resolution single-particle imaging at 100-200 keV with the Gatan Alpine direct electron detector.

Developments in direct electron detector technology have played a pivotal role in enabling high-resolution structural studies by cryo-EM at 200 and 300 keV. Yet, theory and recent experiments indicate advantages to imaging at 100 keV, energies for which the current detectors have not been optimized. In this study, we evaluated the Gatan Alpine detector, designed for operation at 100 and 200 keV. Compared to the Gatan K3, Alpine demonstrated a significant DQE improvement at these voltages, specifically a ~4-fold improvement at Nyquist at 100 keV. In single-particle cryo-EM experiments, Alpine datasets yielded better than 2 Å resolution reconstructions of apoferritin at 120 and 200 keV on a ThermoFisher Scientific (TFS) Glacios microscope. We also achieved a ~3.2 Å resolution reconstruction for a 115 kDa asymmetric protein complex, proving its effectiveness with complex biological samples. In-depth analysis revealed that Alpine reconstructions are comparable to K3 reconstructions at 200 keV, and remarkably, reconstruction from Alpine at 120 keV on a TFS Glacios surpassed all but the 300 keV data from a TFS Titan Krios with GIF/K3. Additionally, we show Alpine's capability for high-resolution data acquisition and screening on lower-end systems by obtaining ~3 Å resolution reconstructions of apoferritin and aldolase at 100 keV and detailed 2D averages of a 55 kDa sample using a side-entry cryo holder. Overall, we show that Gatan Alpine performs well with the standard 200 keV imaging systems and may potentially capture the benefits of lower accelerating voltages, possibly bringing smaller sized particles within the scope of cryo-EM.

Post-acute care and vertical integration after the Patient Protection and Affordable Care Act.

The anticipated changes resulting from the passage of the Patient Protection and Affordable Care Act-including the proposed adoption of bundled payment systems and the promotion of accountable care organizations-have generated considerable controversy as U.S. healthcare industry observers debate whether such changes will motivate vertical integration activity. Using examples of accountable care organizations and bundled payment systems in the American post-acute healthcare sector, this article applies economic and sociological perspectives from organization theory to predict that as acute care organizations vary in the degree to which they experience environmental uncertainty, asset specificity, and network embeddedness, their motivation to integrate post-acute care services will also vary, resulting in a spectrum of integrative behavior.

To make or buy patient safety solutions: a resource dependence and transaction cost economics perspective.

BACKGROUND: For almost a decade, public and private organizations have pressured hospitals to improve their patient safety records. Since 2008, the Centers for Medicare & Medicaid Services has no longer been reimbursing hospitals for secondary diagnoses not reported during the point of admission. This ruling has motivated some hospitals to engage in safety-oriented programs to decrease adverse events. PURPOSE: This study examined which hospitals may engage in patient safety solutions and whether they create these patient safety solutions within their structures or use suppliers in the market. METHODOLOGY: We used a theoretical model that incorporates the key constructs of resource dependence theory and transaction cost economics theory to predict a hospital's reaction to Centers for Medicare & Medicaid Services "never event" regulations. We present propositions that speculate on how forces conceptualized from the resource dependence theory may affect adoption of patient safety innovations and, when they do, whether the adopting hospitals will do so internally or externally according to the transaction cost economics theory. FINDINGS: On the basis of forces identified by the resource dependence theory, we predict that larger, teaching, safety net, horizontally integrated, highly interdependent, and public hospitals in concentrated, high public payer presence, competitive, and resource-rich environments will be more likely to engage in patient safety innovations. Following the logic of the transaction cost economics theory, we predict that of the hospitals that react positively to the never event regulation, most will internalize their innovations in patient safety solutions rather than approach the market, a choice that helps hospitals economize on transaction costs. PRACTICE IMPLICATIONS: This study helps hospital managers in their strategic thinking and planning in relation to current and future regulations related to patient safety. For researchers and policy analysts, our propositions provide the basis for empirical testing.

Accountable Care Organizations and Transaction Cost Economics.

Using a Transaction Cost Economics (TCE) approach, this paper explores which organizational forms Accountable Care Organizations (ACOs) may take. A critical question about form is the amount of vertical integration that an ACO may have, a topic central to TCE. We posit that contextual factors outside and inside an ACO will produce variable transaction costs (the non-production costs of care) such that the decision to integrate vertically will derive from a comparison of these external versus internal costs, assuming reasonably rational management abilities. External costs include those arising from environmental uncertainty and complexity, small numbers bargaining, asset specificity, frequency of exchanges, and information "impactedness." Internal costs include those arising from human resource activities including hiring and staffing, training, evaluating (i.e., disciplining, appraising, or promoting), and otherwise administering programs. At the extreme, these different costs may produce either total vertical integration or little to no vertical integration with most ACOs falling in between. This essay demonstrates how TCE can be applied to the ACO organization form issue, explains TCE, considers ACO activity from the TCE perspective, and reflects on research directions that may inform TCE and facilitate ACO development.

The influence of institutional pressures on hospital electronic health record presence.

Electronic health records (EHR) are a promising form of health information technology that could help US hospitals improve on their quality of care and costs. During the study period explored (2005-2009), high expectations for EHR diffused across institutional stakeholders in the healthcare environment, which may have pressured hospitals to have EHR capabilities even in the presence of weak technical rationale for the technology. Using an extensive set of organizational theory-specific predictors, this study explored whether five factors - cause, constituents, content, context, and control - that reflect the nature of institutional pressures for EHR capabilities motivated hospitals to comply with these pressures. Using information from several national data bases, an ordered probit regression model was estimated. The resulting predicted probabilities of EHR capabilities from the empirical model's estimates were used to test the study's five hypotheses, of which three were supported. When the underlying cause, dependence on constituents, or influence of control were high and potential countervailing forces were low, hospitals were more likely to employ strategic responses that were compliant with the institutional pressures for EHR capabilities. In light of these pressures, hospitals may have acquiesced, by having comprehensive EHR capabilities, or compromised, by having intermediate EHR capabilities, in order to maintain legitimacy in their environment. The study underscores the importance of our assessment for theory and policy development, and provides suggestions for future research.

Primary care service areas: a new tool for the evaluation of primary care services.

OBJECTIVE: To develop and characterize utilization-based service areas for the United States which reflect the travel of Medicare beneficiaries to primary care clinicians. DATA SOURCE/STUDY SETTING: The 1996-1997 Part B and 1996 Outpatient File primary care claims for fee-for-service Medicare beneficiaries aged 65 and older. The 1995 Medicaid claims from six states (1995) and commercial claims from Blue Cross Blue Shield of Michigan (1996). STUDY DESIGN: A patient origin study was conducted to assign 1999 U.S. zip codes to Primary Care Service Areas on the basis of the plurality of beneficiaries' preference for primary care clinicians. Adjustments were made to establish geographic contiguity and minimum population and service localization. Generality of areas to younger populations was tested with Medicaid and commercial claims. DATA COLLECTION/EXTRACTION METHODS: Part B primary care claims were selected on the basis of provider specialty, place of service, and CPT code. Selection of Outpatient File claims used provider number, type of facility/service, and revenue center codes. PRINCIPAL FINDINGS: The study delineated 6,102 Primary Care Service Areas with a median population of 17,276 (range 1,005-1,253,240). Overall, 63 percent of the Medicare beneficiaries sought the plurality of their primary care from within area clinicians. Service localization compared to Medicaid (six states) and commercial primary care utilization (Michigan) was comparable but not identical. CONCLUSIONS: Primary Care Service Areas are a new tool for the measurement of primary care resources, utilization, and associated outcomes. Policymakers at all jurisdictional levels as well as researchers will have a standardized system of geographical units through which to assess access to, supply, use, organization, and financing of primary care services.

Why do some primary care practices engage in practice improvement efforts whereas others do not?

OBJECTIVE: To understand what motivates primary care practices to engage in practice improvement, identify external and internal facilitators and barriers, and refine a conceptual framework. DATA SOURCES: In-depth interviews and structured telephone surveys with clinicians and practice staff (n = 51), observations, and document reviews. STUDY DESIGN: Comparative case study of primary care practices (n = 8) to examine aspects of the practice and environment that influence engagement in improvement activities. DATA COLLECTION METHODS: Three on-site visits, telephone interviews, and two surveys. PRINCIPAL FINDINGS: Pressures from multiple sources create conflicting forces on primary care practices' improvement efforts. Pressures include incentives and requirements, organizational relationships, and access to resources. Culture, leadership priorities, values set by the physician(s), and other factors influence whether primary care practices engage in improvement efforts. CONCLUSIONS: Most primary care practices are caught in a cross fire between two groups of pressures: a set of forces that push practices to remain with the status quo, the "15-minute per patient" approach, and another set of forces that press for major transformations. Our study illuminates the elements involved in the decision to stay with the status quo or to engage in practice improvement efforts needed for transformation.

The relationship between organizational culture and practice systems in primary care.

The patient-centered medical home is an approach to comprehensive primary care relying on well-developed systems. Research has shown that for practices to meet patient-centered medical home requirements, care models may need to be redesigned. However, there is a dearth of information about what factors are important to achieve this goal. Self-report surveys from 293 staff across 42 practices in Minnesota showed variation in use of systems and dimensions of organizational culture. Organizational cultures that emphasize collegiality and quality but not autonomy were significantly related to the use of clinician reminders, clinical quality evaluation and improvement, and clinical information systems.

Medical home infrastructure: effect of the environment and practice characteristics on adoption in Virginia.

This study examined whether environmental factors and practice characteristics influence the existence of patient-centered medical home elements in family practices in Virginia. The study used multiple secondary data sets to measure the external environment and a survey of family practices to enumerate and describe medical home elements and practice environment. Results show a positive association between organizational slack, organizational relationships, and stakeholder expectations on the existence of medical home elements. A negative association was found between competition and medical home elements. Medicare and managed care penetration were not associated with medical home elements. The ability or willingness, or both, of family practices to innovate along the patient-centered medical home model is constrained by important institutional and resource dependencies, and policy makers should take these constraints into account if there is to be widespread adoption of a medical home approach to fee-for-service practices.

A new MEMS-based system for ultra-high-resolution imaging at elevated temperatures.

In recent years, an increasing number of laboratories have been applying in situ heating (and ultimately, gas reaction) techniques in electron microscopy studies of catalysts and other nanophase materials. With the advent of aberration-corrected electron microscopes that provide sub-Angström image resolution, it is of great interest to study the behavior of materials at elevated temperatures while maintaining the resolution capabilities of the microscope. In collaboration with Protochips Inc., our laboratory is developing an advanced capability for in situ heating experiments that overcomes a number of performance problems with standard heating stage technologies. The new heater device allows, for example, temperature cycling from room temperature to greater than 1000 degrees C in 1 ms (a heating rate of 1 million Centigrade degrees per second) and cooling at nearly the same rate. It also exhibits a return to stable operation (drift controlled by the microscope stage, not the heater) in a few seconds after large temperature excursions. With Protochips technology, we were able to demonstrate single atom imaging and the behavior of nanocrystals at high temperatures, using high-angle annular dark-field imaging in an aberration-corrected (S)TEM. The new capability has direct applicability for remote operation and (ultimately) for gas reaction experiments using a specially designed environmental cell.

An improved holey carbon film for cryo-electron microscopy.

Two issues that often impact the cryo-electron microscopy (cryoEM) specimen preparation process are agglomeration of particles near hole edges in holey carbon films and variations in vitreous ice thickness. In many cases, the source of these issues was identified to be the residues and topography often seen in commercially available films. To study and minimize their impact during specimen preparation, an improved holey carbon film has been developed. Rather than using a consumable template based on soft materials that must be removed prior to grid assembly, a method was developed that uses a hard template and a water-soluble release layer to replicate the template pattern into the carbon films. The advantages of this method are the improved purity and flatness of the carbon films, and these attributes are shown to have a dramatic improvement on the distribution of single particles embedded in vitreous ice suspended across the holes. Improving particle distribution is an enabling factor toward increasing the throughput of data collection for cryoEM.

The contribution of organization theory to nursing health services research.

We review nursing and health services research on health care organizations over the period 1950 through 2004 to reveal the contribution of nursing to this field. Notwithstanding this rich tradition and the unique perspective of nursing researchers grounded in patient care production processes, the following gaps in nursing research remain: (1) the lack of theoretical frameworks about organizational factors relating to internal work processes; (2) the need for sophisticated methodologies to guide empirical investigations; (3) the difficulty in understanding how organizations adapt models for patient care delivery in response to market forces; (4) the paucity of attention to the impact of new technologies on the organization of patient care work processes. Given nurses' deep understanding of the inner workings of health care facilities, we hope to see an increasing number of research programs that tackle these deficiencies.