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Recognition of phosphatidylserine (PS) lipids exposed on the extracellular leaflet of plasma membranes is implicated in both apoptotic cell removal and immune regulation. The PS receptor T cell immunoglobulin and mucin-domain-containing molecule 4 (Tim4) regulates T-cell immunity via phagocytosis of both apoptotic (high PS exposure) and nonapoptotic (intermediate PS exposure) activated T cells. The latter population must be removed at lower efficiency to sensitively control immune tolerance and memory cell population size, but the molecular basis for how Tim4 achieves this sensitivity is unknown. Using a combination of interfacial X-ray scattering, molecular dynamics simulations, and membrane binding assays, we demonstrate how Tim4 recognizes PS in the context of a lipid bilayer. Our data reveal that in addition to the known Ca ²⁺-coordinated, single-PS binding pocket, Tim4 has four weaker sites of potential ionic interactions with PS lipids. This organization makes Tim4 sensitive to PS surface concentration in a manner capable of supporting differential recognition on the basis of PS exposure level. The structurally homologous, but functionally distinct, Tim1 and Tim3 are significantly less sensitive to PS surface density, likely reflecting the differences in immunological function between the Tim proteins. These results establish the potential for lipid membrane parameters, such as PS surface density, to play a critical role in facilitating selective recognition of PS-exposing cells. Furthermore, our multidisciplinary approach overcomes the difficulties associated with characterizing dynamic protein/membrane systems to reveal the molecular mechanisms underlying Tim4’s recognition properties, and thereby provides an approach capable of providing atomic-level detail to uncover the nuances of protein/membrane interactions.

\"In celebration of the 50th anniversary of the Apollo 11 landing, the endlessly-mysterious moon is explored in this reprint short science fiction anthology from award-winning editor and anthologist Neil Clarke ... On July 20, 1969, mankind made what had only years earlier seemed like an impossible leap forward: when Apollo 11 became the first manned mission to land on the moon, and Neil Armstrong the first person to step foot on the lunar surface. While there have only been a handful of new missions since, the fascination with our planet's satellite continues, and generations of writers and artists have imagined the endless possibilities of lunar life. From adventures in the vast gulf of space between the earth and the moon, to journeys across the light face to the dark side, to the establishment of permanent residences on its surface, science fiction has for decades given readers bold and forward-thinking ideas about our nearest interstellar neighbor and what it might mean to humankind, both now and in our future. [This book] collects the best stories written in the fifty years since mankind first stepped foot on the lunar surface, serving as a shining reminder that the moon is and always has been our most visible and constant example of all the infinite possibility of the wider universe\"-- Provided by publisher.

[...]being the state's only academic medical center, UMMC had come to embrace its role and responsibility as the leader of health care delivery in the state and developed aspirations to be a regional health care leader alongside other outstanding academic medical centers in the southeast. UMMC was in the process of implementing a newly developed institutional strategic plan designed to further transform the institution's preexisting self-limiting insular approach (with a reputation as the state's charity hospital fueled largely by house staff care) into becoming recognized as a resource jewel for the state, run by faculty physicians offering patient-centric care, especially for those in need of high-end services. UMMC chose \"high reliability\" as the infrastructure on which to build its quality improvement program and began a journey toward becoming a high-reliability organization (HRO).3 Although several entities have espoused high reliability as the basis for driving change, UMMC specifically chose to use the model developed by The Joint Commission's Center for Transforming Healthcare.4 During the prior decade, the Center for Transforming Healthcare developed high-reliability tools that are applicable to health care and was in the process of expanding this work more broadly. Translating this goal to frontline improvement work requires making the gap understandable by converting the publicly reported standardized infection ratio, which is based on a rate per 1000 eligible patients/lines/catheters to the actual number of infections in an agreed time. [...]for a specific HAI, a standardized infection ratio of 1.206 may translate to a baseline of 10 HAIs per month which can then lead to setting a specific improvement target of a reduction such as 6 HAIs per month within 12 months.

Anemia during hospitalization is associated with poor health outcomes. Does anemia at discharge place patients at risk for hospital readmission within 30 days of discharge? Our objectives were to examine the prevalence and magnitude of anemia at hospital discharge and determine whether anemia at discharge was associated with 30-day readmissions among a cohort of hospitalizations in a single health care system. From January 1, 2009, to August 31, 2011, there were 152,757 eligible hospitalizations within a single health care system. The endpoint was any hospitalization within 30 days of discharge. The University HealthSystem Consortium's clinical database was used for demographics and comorbidities; hemoglobin values are from the hospitals' electronic medical records, and readmission status was obtained from the University HealthSystem Consortium administrative data systems. Mild anemia was defined as hemoglobin of greater than 11 to less than 12 g/dl in women and greater than 11 to less than 13 g/dl in men; moderate, greater than 9 to less than or equal to 11 g/dl; and severe, less than or equal to 9 g/dl. Logistic regression was used to assess the association of anemia and 30-day readmissions adjusted for demographics, comorbidity, and hospitalization type. Among 152,757 hospitalizations, 72% of patients were discharged with anemia: 31,903 (21%), mild; 52,971 (35%), moderate; and 25,522 (17%), severe. Discharge anemia was associated with severity-dependent increased odds for 30-day hospital readmission compared with those without anemia: for mild anemia, 1.74 (1.65-1.82); moderate anemia, 2.76 (2.64-2.89); and severe anemia, 3.47 (3.30-3.65), P < 0.001. Anemia at discharge is associated with a severity-dependent increased risk for 30-day readmission. A strategy focusing on anemia treatment care paths during index hospitalization offers an opportunity to influence subsequent readmissions.

Anemia at hospitalization is often treated as an accompaniment to an underlying illness, without active investigation, despite its association with morbidity. Development of hospital-acquired anemia (HAA) has also been associated with increased risk for poor outcomes. Together, they may further heighten morbidity risk from bad to worse. The aims of this study were to (1) examine mortality, length of stay, and total charges in patients with present-on-admission (POA) anemia and (2) determine whether these are exacerbated by development of HAA. In this cohort investigation, from January 1, 2009, to August 31, 2011, a total of 44,483 patients with POA anemia were admitted to a single health system compared with a reference group of 48,640 without POA anemia or HAA. Data sources included the University HealthSystem Consortium database and electronic medical records. Risk-adjustment methods included logistic and linear regression models for mortality, length of stay, and total charges. Present-on-admission anemia was defined by administrative coding. Hospital-acquired anemia was determined by changes in hemoglobin values from the electronic medical record. Approximately one-half of the patients experienced worsening of anemia with development of HAA. Risk for death and resource use increased with increasing severity of HAA. Those who developed severe HAA had 2-fold greater odds for death; that is, mild POA anemia with development of severe HAA resulted in greater mortality (odds ratio, 2.57; 95% confidence interval, 2.08-3.18; P < 0.001), increased length of stay (2.23; 2.16-2.31; P < 0.001), and higher charges (2.09; 2.03-2.15; P < 0.001). Present-on-admission anemia is associated with increased mortality and resource use. This risk is further increased from bad to worse when patients develop HAA. Efforts to address POA anemia and HAA deserve attention.

We investigated patterns of use of alcohol and its clinical effects among cirrhotic subjects who participated in a randomized clinical trial comparing the efficacy of transjugular intravenous portosystemic shunt and distal splenorenal shunt. There were 132 cirrhotic subjects, 78 with alcoholic liver disease (ALD), who were followed for a median of 49 months (range 2-93 months). Alcohol use was assessed by patient questionnaire, with corroboration by family members. Twenty-eight subjects (21%) were drinking at study entry and 60 subjects (45%) drank during follow-up. Heavy drinking (>4 drinks/day) was recorded in 25 ALD subjects, but in no non-ALD subjects (P < 0.0001). Drinking by ALD subjects was associated with a 153% increase in gamma-glutamyl transpeptidase (GGT) (P < 0.0001). The frequencies of death (46%vs 30%), ascites (33%vs 20%), encephalopathy (56%vs 42%), and variceal bleeding (11%vs 3%) were greater in the ALD group. In a Cox proportional hazards model only \"ever heavy drinking\" was associated with death (P= 0.0099), while recent heavy drinking increased the hazard of variceal hemorrhage dramatically (odds ratio 10.85). Whereas most cirrhotic subjects, alcoholic or not, did not drink during 5 yr of observation, heavy alcohol use occurred exclusively in ALD patients. Alcohol use by ALD subjects was associated with elevations in GGT and was linked to death and with rebleeding from shunt dysfunction.

OBJECTIVESWe will provide a context to health information technology systems (HIT) safety hazards discussions, describe how electronic health record–computer prescriber order entry (EHR-CPOE) simulation has already identified unrecognized hazards in HIT on a national scale, helping make EHR-CPOE systems safer, and we make the case for all stakeholders to leverage proven methods and teams in HIT performance verification. METHODSA national poll of safety, quality improvement, and health-care administrative leaders identified health information technology safety as the hazard of greatest concern for 2013. Quality, HIT, and safety leaders are very concerned about technology performance risks as addressed in the Health Information Technology and Patient Safety report of the Institute of Medicine; and these are being addressed by the Office of the National Coordinator of HIT of the U.S. Dept. of Human Services in their proposed plans. We describe the evolution of postdeployment testing of HIT performance, including the results of national deployment of Texas Medical Institute of Technology’s electronic health record computer prescriber order entry (TMIT EHR-CPOE) Flight Simulator verification test that is addressed in these 2 reports, and the safety hazards of concern to leaders. RESULTSA global webinar for health-care leaders addressed the top patient safety hazards in the areas of leadership, practices, and technologies. A poll of 76 of the 221 organizations participating in the webinar revealed that HIT hazards were the participants’ greatest concern of all 30 hazards presented. Of those polled, 89% rated HIT patient/data mismatches in EHRs and HIT systems as a 9 or 10 on a scale of 1 to 10 as a hazard of great concern. Review of a key study of postdeployment testing of the safety performance of operational EHR systems with CPOE implemented in 62 hospitals, using the TMIT EHR-CPOE simulation tool, showed that only 53% of the medication orders that could have resulted in fatalities were detected. The study also showed significant variability in the performance of specific EHR vendor systems, with the same vendor product scoring as high as a 75% detection score in one health-care organization, and the same vendor system scoring below 10% in another health-care organization. CONCLUSIONSHIT safety hazards should be taken very seriously, and the need for proven, robust, and regular postdeployment performance verification measurement of EHR system operations in every health-care organization is critical to ensure that these systems are safe for every patient. The TMIT EHR-CPOE flight simulator is a well-tested and scalable tool that can be used to identify performance gaps in EHR and other HIT systems. It is critical that suppliers, providers, and purchasers of health-care partner with HIT stakeholders and leverage the existing body of work, as well as expert teams and collaborative networks to make care safer; and public-private partnerships to accelerate safety in HIT. A global collaborative is already underway incorporating a “trust but verify” philosophy.

Position your organisation's culture to attain new heights Above the Line: How to Create a Company Culture that Engages Employees, Delights Customers and Delivers Results offers all leaders a handbook for leveraging an organisation's culture to engage staff, increase customer satisfaction and streamline business performance. A groundbreaking work, this book reveals what it takes to achieve optimum results from your organisational culture without employing the use of external consultants. This organic, in-house approach to company culture transformation saves both time and money. Step-by-step, author Michael Henderson illustrates how to create a culture in which employees and leaders delight those outside the company-customers, shareholder, employees' families, suppliers and the board of directors-and anyone else who may benefit from an association with the organisation. The book's proven models and ideas have been tried and tested with a broad range of of high-profile international companies. Expert author, Michael Henderson, a.k.a. The Corporate Anthropologist, has more than 30 years' experience, and a proven track record of working and consulting with organisations to enhance their workplace cultures. Reveals how to create an organisational culture that achieves desired results Puts the cultural transformation process in the hands of the people directly effected Smashes some of the established and costly myths about culture and how to work with culture This important resource is written for leaders, managers and supervisors at all levels and across industries.