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OBJECTIVE: To establish an enterprise initiative for improving health and health care through interoperable electronic health record (EHR) innovations. MATERIALS AND METHODS: We developed a unifying mission and vision, established multidisciplinary governance, and formulated a strategic plan. Key elements of our strategy include establishing a world-class team; creating shared infrastructure to support individual innovations; developing and implementing innovations with high anticipated impact and a clear path to adoption; incorporating best practices such as the use of Fast Healthcare Interoperability Resources (FHIR) and related interoperability standards; and maximizing synergies across research and operations and with partner organizations. RESULTS: University of Utah Health launched the ReImagine EHR initiative in 2016. Supportive infrastructure developed by the initiative include various FHIR-related tooling and a systematic evaluation framework. More than 10 EHR-integrated digital innovations have been implemented to support preventive care, shared decision-making, chronic disease management, and acute clinical care. Initial evaluations of these innovations have demonstrated positive impact on user satisfaction, provider efficiency, and compliance with evidence-based guidelines. Return on investment has included improvements in care; over $35 million in external grant funding; commercial opportunities; and increased ability to adapt to a changing healthcare landscape. DISCUSSION: Key lessons learned include the value of investing in digital innovation initiatives leveraging FHIR; the importance of supportive infrastructure for accelerating innovation; and the critical role of user-centered design, implementation science, and evaluation. CONCLUSION: EHR-integrated digital innovation initiatives can be key assets for enhancing the EHR user experience, improving patient care, and reducing provider burnout.

Type I diabetes is caused by the autoimmune destruction of pancreatic beta (â) cells [1]. Current treatment requires multiple daily injections of insulin to control blood glucose levels. Tight glucose control lowers, but does not eliminate, the onset of diabetic complications, which greatly reduce the quality and longevity of life for patients. Transplantation of pancreatic tissue as a treatment is restricted by the scarcity of donors and the requirement for lifelong immunosuppression to preserve the graft, which carries adverse side-effects. This is of particular concern as Type 1 diabetes predominantly affects children. Lack of glucose control could be overcome by genetically engineering "an artificial â-cell" that is capable of synthesising, storing and secreting insulin in response to metabolic signals. The donor cell type must be readily accessible and capable of being engineered to synthesise, process, store and secrete insulin under physiological conditions.

The ability to visualise proteins in their native environment and discern information regarding stoichiometry is of critical importance when studying protein interactions and function. We have used liquid cell atomic force microscopy (AFM) to visualise proteins in their native state in buffer and have determined their molecular volumes. The human proteins S100A8, S100A9, S100A12 and CLIC1 were used in this investigation. The effect of oxidation on the protein structure of CLIC1 was also investigated and we found that CLIC1 multimerisation could be discerned by AFM, which supports similar findings by other methods. We have found good correlation between the molecular volumes measured by AFM and the calculated volumes of the individual proteins. This method allows for the study of single soluble proteins under physiological conditions and could potentially be extended to study the structure of these proteins when located within a membrane environment.

BACKGROUND: In healthcare today, decisions are made in the face of serious resource constraints. Healthcare managers are struggling to provide high quality care, manage resources effectively, and meet changing patient needs. Healthcare managers who are constantly making difficult resource decisions desire a way to improve their priority setting processes. Despite the wealth of existing priority setting literature (for example, program budgeting and marginal analysis, accountability for reasonableness, the 'describe-evaluate-improve' strategy) there are still no tools to evaluate how healthcare resources are prioritised. This paper describes the development and piloting of a process to evaluate priority setting in health institutions. The evaluation process was designed to examine the procedural and substantive dimensions of priority setting using a multi-methods approach, including a staff survey, decision-maker interviews, and document analysis. METHODS: The evaluation process was piloted in a mid-size community hospital in Ontario, Canada while its leaders worked through their annual budgeting process. Both qualitative and quantitative methods were used to analyze the data. RESULTS: The evaluation process was both applicable to the context and it captured the budgeting process. In general, the pilot test provided support for our evaluation process and our definition of success, (i.e., our conceptual framework). CONCLUSIONS: The purpose of the evaluation process is to provide a simple, practical way for an organization to better understand what it means to achieve success in its priority setting activities and identify areas for improvement. In order for the process to be used by healthcare managers today, modification and contextualization of the process are anticipated. As the evaluation process is applied in more health care organizations or applied repeatedly in an organization, it may become more streamlined.

BACKGROUND: The sustainability of healthcare systems worldwide is threatened by a growing demand for services and expensive innovative technologies. Decision makers struggle in this environment to set priorities appropriately, particularly because they lack consensus about which values should guide their decisions. One way to approach this problem is to determine what all relevant stakeholders understand successful priority setting to mean. The goal of this research was to develop a conceptual framework for successful priority setting. METHODS: Three separate empirical studies were completed using qualitative data collection methods (one-on-one interviews with healthcare decision makers from across Canada; focus groups with representation of patients, caregivers and policy makers; and Delphi study including scholars and decision makers from five countries). RESULTS: This paper synthesizes the findings from three studies into a framework of ten separate but interconnected elements germane to successful priority setting: stakeholder understanding, shifted priorities/reallocation of resources, decision making quality, stakeholder acceptance and satisfaction, positive externalities, stakeholder engagement, use of explicit process, information management, consideration of values and context, and revision or appeals mechanism. CONCLUSION: The ten elements specify both quantitative and qualitative dimensions of priority setting and relate to both process and outcome components. To our knowledge, this is the first framework that describes successful priority setting. The ten elements identified in this research provide guidance for decision makers and a common language to discuss priority setting success and work toward improving priority setting efforts.

The development of nanostructured microcapsules based on a biomimetic lipid bilayer membrane (BLM) coating of poIy(sodium styrenesutfbnate) (PSS)/poIy(alIylamine hydrochloride) (PAH) polyelectrolyte hollow microcapsules is reported. A novel engineered ion channel, gramicidin (bisgA), incorporated into the lipid membrane coating provides a functional capability to control transport across the microcapsule wall. The microcapsules provide transport and permeation for drug-analog neutral species, as well as positively and negatively charged ionic species. This controlled transport can be tuned for selective release biomimetically by controlling the gating of incorporated bis-gA ion channels. This system provides a platform for the creation of "smart" biomimetic delivery vessels for the effective and selective therapeutic delivery and targeting of drugs. © 2009 WILEY-VCH Verlag GmbH & Co. KGaA.

In this paper the authors describe the implementation and validation of a prototype of an environmental and health monitoring system based on a Wireless Sensor Network (WSN). The solution proposed for our system combines environmental and medical sensors in order to monitor both the surrounding area of the patient and the patients health status simultaneously. This feature would allow a comprehensive understanding of the patients condition by the specialist caring for the subject. Another key feature of the system is the development of an architecture which provides an easy, viable, cheap and effective way for connecting our environmental and medical sensor network of MicaZ motes to the outside world using Simple Network Management Protocol (SNMP) version 3. A series of experimental scenarios were developed and implemented in a laboratory setting; firstly for evaluating the reactivity of the monitoring system to changes and secondly for understanding the reliability of the data obtained for benchmarking purposes. The conclusion considers the implementation of future improvements to the health monitoring network by introducing new sensors and location tracking capabilities, and by integrating alarm triggering algorithms and advanced security techniques.

The normal function of retinal capillaries to distribute blood within the retina depends on appropriate contractility of retinal pericytes, which is thought to be modulated by agents that alter intracellular cyclic adenosine-3'-monophosphate (cAMP) levels. We examined the hypothesis that the vasoactive peptides Vasoactive Intestinal Peptide (VIP) and Pituitary Adenylate Cyclase Activating Peptide (PACAP) reduce pericyte contractility via a protein kinase A (PKA)-mediated intracellular pathway that utilises cAMP. We utilised a single-call assay of contractility that is based on visualising the contractile force exerted by the pericytes on a silicone elastomer substrate and quantified, as a contractility index, from the number and length of wrinkles induced in the silicone elastomer by the pericytes. Pericytes were cultured from the retinas of freshly killed abattoir cattle, and identified in culture using immunohistochemical techniques. The pericytes contracted in response to norepinephrine (EC(50)=8 microM) and relaxed in response to both VIP (EC(50)=48 nM) and PACAP (EC(50)=3 nM). The relaxation induced by PACAP was inhibited by Rp-cAMPS (EC(50)=26 microM), which is an agent that inhibits cAMP binding at PKA. We confirmed the activation of PKA by PACAP in experiments where H89 also inhibited the PACAP-induced relaxation. U71322, which inhibits phospholipase C-linked events, was also able to inhibit the PACAP-induced pericyte relaxation. Our results support the hypothesis that PACAP leads to the relaxation of pericytes via a PKA-mediated intracellular pathway and a phospholipase C-mediated pathway, which probably relies on hyperpolarisation because of activation of Ca(2+)-dependent potassium channels. This single-cell assay has proved useful as the basis for the development of a diagnostic procedure for diabetic retinopathy, which is an eye disease caused by abnormal regulation of blood flow in the retinal capillaries.

The application of nanotechnology principles and methodology to problems in biotechnology is providing an exciting discipline that will generate a revolution of novel applications in several arenas. Applications of nanotechnology range from novel nanosensors, to novel methods for sorting and delivering bioactive molecules, to novel drug-delivery systems. The philosophical approaches to findingsolutions to those application areas historically have reliedon engineering and the physical sciences to produce materials and processes that are then tested for efficacy in the biological environment. The difficulty in that approach is that it relies on an entirelyempiricalprocess in testing new materials or processes for compatibility in biological systems, and then subsequently for ultimatetesting of the new material or process in humans. Whilst ourintention with this book is not to denigrate the philosophy of that approach, nor to make claims that biological systems are completely predictable and thus able to be entirely modelled, the alternative approach that this book aims to address is that of nanobiotechnology. Put simply, the alternative that nanobiotechnology offers is to more closely utilise biological principles in guiding and influencing the materials and processes that are developed from engineering and the physical sciences for use in medical applications.

This paper deals with the experimental construction, stochastic modeling, and statistical signal processing of a novel, artificially constructed biosensor comprised of biological ion channels. Such nanoscale biosensors have been built by incorporating dimeric gramicidin A (bis-gA) ion channels into bilayer membranes of giant unilamellar liposomes, and then excising small patches of the membrane loaded with ion channels. We present a stochastic model for the response of the biosensor and present statistical model validation tests to verify the adequacy of the model. We show that in the presence of specific target molecules, the statistics of the gating mechanisms of the gA channels are altered. By capturing the change in real time, we devise a maximum-likelihood detector to detect the presence of target molecules. To test the sensitivity of this model, we conducted patch-clamp experiments with two compounds known to inhibit conduction of the gA channels. We found experimentally that the real-time detection algorithm was able to accurately identify the addition of the compounds even when the alterations in the patch-clamp recordings were very small. This algorithm provides the sensitive detection system for ongoing development of lipid-based nanosensors. © 2007 IEEE.

Titanium nitride thin films are widely used in biomedical implants because of their biocompatibility, good mechanical properties and high corrosion resistance. Titanium nitride (TiN) thin films on silicon and glass substrates were prepared using a dc magnetron sputtering system under conditions of systematically varying the nitrogen pressure and titanium magnetron power. The nano-structure and microstructure of the coatings was examined using a scanning electron microscope and atomic force microscope. The present studies show that the surface structure, grain size, deposition rate and microhardness of the coatings are strongly dependent on the nitrogen pressure and titanium magnetron power. The grain diameter increased from 35 to 100 nm with the increase in nitrogen partial pressure from 0.4 to 1.0 mTorr. The optimal nitrogen partial pressure found for making gold colour TiN thin films and increased hardness (about 2550 Vickers number) was determined to be between 0.4 - 0.6 mTorr. The grain size was found to decrease from 60 to 28 nm and the microhardness increased from 1600 to 2550 (Vickers number) as the titanium magnetron power increased from 100 to 250 W. © Institute of Materials Engineering Australasia Ltd.

This is the first study to systematically identify and prioritize which applications of regenerative medicine are the most promising for improving health in developing countries.

S100 proteins are important Ca2+-binding proteins involved in vital cellular functions including the modulation of cell growth, migration and differentiation, regulation of intracellular signal transduction/ phosphorylation pathways, energy metabolism, cytoskeletal interactions and modulation of ion channels. Furthermore, they are implicated in oncogenesis and numerous other disease states. Three S100 proteins: S100A8, S100A9 and S100A12 are constitutively expressed in neutrophils and monocytes. At low levels of intracellular Ca2+, S100A8 and S100A9 are located predominantly in the cytosol but when Ca2+ concentrations are elevated as a consequence of activation, they translocate to membranes and complex with cytoskeletal components such as vimentin. The functions of S100A8 and S100A9 at the plasma membrane remain unclear. A possible role may be the regulation of ion channel proteins. The current study uses the techniques of Atomic Force Microscopy and production of artificial lipid membranes in the form of liposomes to investigate possible mechanisms for the insertion of these proteins into membranes in order to elucidate their structure and stoichiometry in the transmembrane state. We have successfully imaged the liposomes as a lipid bilayer, the S100A8/A9 protein complex in solution and the S100A8/A9 complex associating with lipid, using tapping-mode atomic force microscopy, in buffer.

The use of mobile phones is increasing, which also increases the population's exposure to global system of mobile communications (GSM) signals. Questions of safety and possible biological effects are of concern and to date, remain largely unanswered. In order to examine possible biological effects of a GSM-like signal at a cellular level, we exposed two human cell lines (one of neuronal (SK-N-SH) and the other of monocytoid (U937) origin) to a 900 MHz RF signal, pulsed at 217 Hz, producing a specific absorption rate (SAR) of 0.2 W/kg. Putative effects were assessed by comparing radiofrequency-exposed cells to sham-exposed cells using a variety of assay techniques. For the cell line SK-N-SH, effects were specifically assessed by gene microarray, followed by real-time PCR of the genes of interest, Western blot analysis was used to measure heat shock protein levels, and flow cytometry to measure cell cycle distributions and apoptosis. Effects of radiofrequency on the cell line U937 were assessed by cell viability and cell cycle analysis. From our study of these two cell lines, we found no significant difference between sham-exposed versus radiofrequency-exposed cells in any of the assays or conditions examined. © 2006 International Federation for Cell Biology.

We have constructed liposomes from L-alpha-Phosphatidylcholine (PC) lipids, which are biomimetic lipids similar to those present in the membranes of mammalian cells. We propose an advance in the use of liposomes, such as for drug delivery, to incorporate into the liposomal membranes transport proteins that have been extracted from the lipid membranes of mammalian cells. In this paper, we describe the usage of a novel optical microscope to characterize the nanomechanical properties of these liposomes. We have applied the technique of digital holographic microscopy1, using an instrument recently developed at the University of Münster, Germany. This system enabled us to measure quantitatively the structural changes in liposomes. We have investigated the deformations of these biomimetic lipids comprising these liposomes by applying osmotic stresses, in order to gain insight into the membrane environment prior to incorporation of cloned membrane transport proteins. This control of the nanomechanical properties is important in the stresses transmitted to mechanosensitive ion channels that we have incorporated into the liposomal membranes. These liposomes provide transporting vesicles that respond to mechanical stresses, such as those that occur during implantation.

How nanotechnology can be harnessed to address some of the world's most critical development problems

BACKGROUND: Priority setting, also known as rationing or resource allocation, occurs at all levels of every health care system. Daniels and Sabin have proposed a framework for priority setting in health care institutions called 'accountability for reasonableness', which links priority setting to theories of democratic deliberation. Fairness is a key goal of priority setting. According to 'accountability for reasonableness', health care institutions engaged in priority setting have a claim to fairness if they satisfy four conditions of relevance, publicity, appeals/revision, and enforcement. This is the first study which has surveyed the views of hospital decision makers throughout an entire health system about the fairness of priority setting in their institutions. The purpose of this study is to elicit hospital decision-makers' self-report of the fairness of priority setting in their hospitals using an explicit conceptual framework, 'accountability for reasonableness'. METHODS: 160 Ontario hospital Chief Executive Officers, or their designates, were asked to complete a survey questionnaire concerning priority setting in their publicly funded institutions. Eight-six Ontario hospitals completed this survey, for a response rate of 54%. Six close-ended rating scale questions (e.g. Overall, how fair is priority setting at your hospital?), and 3 open-ended questions (e.g. What do you see as the goal(s) of priority setting in your hospital?) were used. RESULTS: Overall, 60.7% of respondents indicated their hospitals' priority setting was fair. With respect to the 'accountability for reasonableness' conditions, respondents indicated their hospitals performed best for the relevance (75.0%) condition, followed by appeals/revision (56.6%), publicity (56.0%), and enforcement (39.5%). CONCLUSIONS: For the first time hospital Chief Executive Officers within an entire health system were surveyed about the fairness of priority setting practices in their institutions using the conc

BACKGROUND: Hospitals and regional health authorities must set priorities in the face of resource constraints. Decision-makers seek practical ways to set priorities fairly in strategic planning, but find limited guidance from the literature. Very little has been reported from the perspective of Board members and senior managers about what criteria, processes and parameters of success they would use to set priorities fairly. DISCUSSION: We facilitated workshops for board members and senior leadership at three health care organizations to assist them in developing a strategy for fair priority setting. Workshop participants identified 8 priority setting criteria, 10 key priority setting process elements, and 6 parameters of success that they would use to set priorities in their organizations. Decision-makers in other organizations can draw lessons from these findings to enhance the fairness of their priority setting decision-making. SUMMARY: Lessons learned in three workshops fill an important gap in the literature about what criteria, processes, and parameters of success Board members and senior managers would use to set priorities fairly.

BACKGROUND: While the desirability of interdisciplinary inquiry has been widely acknowledged, indeed has become 'the mantra of science policy', the methods of interdisciplinary collaboration are opaque to outsiders and generally remain undescribed. DISCUSSION: Many have analysed interdisciplinarity, especially in relation to the creation of new disciplines and institutions. These analyses are briefly outlined. Still, there currently persists a silence about the methods of interdisciplinary collaboration itself, and the core of this paper proposes a template for such methods. SUMMARY: Breaking this silence--by making the methods of interdisciplinary projects transparent--could further invigorate interdisciplinary research.

BACKGROUND: Decision makers in health care organizations struggle with how to set priorities for new technologies in medicine. Traditional approaches to priority setting for new technologies in medicine are insufficient and there is no widely accepted model that can guide decision makers. DISCUSSION: Daniels and Sabin have developed an ethically based account about how priority setting decisions should be made. We have developed an empirically based account of how priority setting decisions are made. In this paper, we integrate these two accounts into a transdisciplinary model of priority setting for new technologies in medicine that is both ethically and empirically based. SUMMARY: We have developed a transdisciplinary model of priority setting that provides guidance to decision makers that they can operationalize to help address priority setting problems in their institution.

BACKGROUND: Why waiting lists arise and how to address them remains unclear, and an improved understanding of these waiting list "dynamics" could lead to better management. The purpose of this study is to understand how the current shortage in radiation therapy in Ontario developed; the implications of prolonged waits; who is held accountable for managing such delays; and short, intermediate, and long-term solutions. METHODS: A case study of the radiation therapy shortage in 1998-99 at Princess Margaret Hospital, Toronto, Ontario, Canada. Relevant documents were collected; semi-structured, face-to-face interviews with ten administrators, health care workers, and patients were conducted, audio-taped and transcribed; and relevant meetings were observed. RESULTS: The radiation therapy shortage arose from a complex interplay of factors including: rising cancer incidence rates; broadening indications for radiation therapy; human resources management issues; government funding decisions; and responsiveness to previous planning recommendations. Implications of delays include poorer cancer control rates; patient suffering; and strained doctor-patient relationships. An incompatible relationship exists between moral responsibility, borne by government, and legal liability, borne by physicians. Short-term solutions include re-referral to centers with available resources; long-term solutions include training and recruiting health care workers, improving workload standards, increasing compensation, and making changes to the funding formula. CONCLUSION: Human resource planning plays a critical role in the causes and solutions of waiting lists. Waiting lists have harsh implications for patients. Accountability relationships require realignment.

Ion channels are known to be present on the plasma membrane of virtually all cells and have been found on the membranes of various intracellular organelles. However, until recently they were believed not to occur at the nuclear membrane. In this study we describe the molecular cloning and characterization of a nuclear ion channel protein, designated nuclear chloride channel-27 (NCC27), from the human myelomonocytic cell line, U937. NCC27 is a novel chloride ion channel protein that was found to localize principally to the cell nucleus. Its only known homologue is a bovine chloride ion channel protein (p64) believed to localize to internal organelles. NCC27 therefore represents the first human member of a new class of organella chloride ion channel proteins.

This paper describes an electronic device for the measurement of the diameter of the tip opening of micropipettes. The device measures the threshold pressure required to produce bubbles from the micropipette submerged in a liquid and displays the tip inner diameter in micrometres. We demonstrate that this technique can be used effectively in a range of liquids of different density, surface tension and viscosity and that the thickness of the glass from which the micropipettes are made does not influence the measurements.