Functional and physiological role of vitamin C transporters

Vitamin C (ascorbic acid) is required for the synthesis of collagen, carnitine, catecholamine and the neurotransmitter norepinephrine. Vitamin C also plays an important role in protection against oxidative stress. Transporters for vitamin C and its oxidized form dehydroascorbate (DHA) are crucial to keep vitamin concentrations optimal in the body. The human SLC23 family consists of the Na(+)-dependent vitamin C transporters SVCT1 (SLC23A1) and SVCT2 (SLC23A2) and the orphan transporter SVCT3 (SLC23A3). Phylogenetically, the SLC23 family belongs to the nucleobase-ascorbate transporter family although no specificity for nucleobases has yet been demonstrated for the human members of this family. In fact, the SVCT1 and SVCT2 transporters are rather specific for ascorbic acid. SVCT1 is expressed in epithelial tissues such as intestine, where it contributes to the maintenance of whole-body ascorbic acid levels, whereas the expression of SVCT2 is relatively widespread either to protect metabolically active cells and specialized tissues from oxidative stress or to deliver ascorbic acid to tissues that are in high demand of the vitamin for enzymatic reactions. DHA, the oxidized form of ascorbic acid is taken up and distributed in the body by facilitated transport via members of the SLC2/GLUT family (GLUT1, GLUT3, and GLUT4). Although, the main focus of this review is on the SLC23 family of ascorbic acid transporters, transporters of DHA and nucleobases are also briefly discussed for completeness.

A Method for Assessing the Sustainability of Design in Developing World Projects

Projects for the developing world usually find themselves at the bottom of an engineer’s priority list. There is often very little engineering effort placed on creating new products for the poorest people in the world. This trend is beginning to change now as people begin to recognize the potential for these projects. Engineers are beginning to try and solve some of the direst issues in the developing world and many are having positive impacts. However, the conditions needed to support these projects can only be maintained in the short term. There is now a need for greater sustainability. Sustainability has a wide variety of definitions in both business and engineering. These concepts are analyzed and synthesized to develop a broad meaning of sustainability in the developing world. This primarily stems from the “triple bottom line” concept of economic, social, and environmental sustainability. Using this model and several international standards, this thesis develops a metric for guiding and evaluating the sustainability of engineering projects. The metric contains qualitative questions that investigate the sustainability of a project. It is used to assess several existing projects in order to determine flaws. Specifically, three projects seeking to deliver eyeglasses are analyzed for weaknesses to help define a new design approach for achieving better results. Using the metric as a guiding tool, teams designed two pieces of optometry equipment: one to cut lenses for eyeglasses and the other to diagnose refractive error, or prescription. These designs are created and prototyped in the developed and developing worlds in order to determine general feasibility. Although there is a recognized need for eventual design iterations, the whole project is evaluated using the developed metric and compared to the existing projects. Overall, the success demonstrates the improvements made to the long-term sustainability of the project resulting from the use of the sustainability metric.

Training in Mental Health: Evaluation of the Telephone Conference Network

The Telephone Conference Network, sponsored by The Pennsylvania State University's Coordinating Council for Health Care, is designed as a cost-effective format for providing inservice training in geriatric mental health for individuals who serve the elderly. Institutions which subscribe to the Telephone Conference Network are equipped with a conference speaker and telephone hook-up providing a two-way line of communication, and may choose from a variety of inservice programs. Mailed evaluations were completed by participants (N=73) in the "Skills to Manage Moods" program, a series of four 1-hour sessions designed to teach participants the skills needed to help patients cope with depression and to deliver the program to others. The majority of respondents reported high levels of satisfaction with the Telephone Conference Network system and the specific program in which they participated. Although 85 percent reported that they would be able to use the skills learned in the program on the job, 50 percent reported that they would not be interested in teaching these skills to others. The convenience and efficiency of the Telephone Conference Network were the most frequently mentioned strengths of the system, while the physical facilities and the program delivery format adopted by the individual institutions were the most frequently mentioned weaknesses. These data suggested several recommendations for Network subscribers and for professionals offering telephone conference programs, including ensuring optimal class enrollment and adequate physical facilities, and participant involvement in program implementation.

Screening for sleep disorders in community pharmacies--evaluation of a campaign in Switzerland

BACKGROUND: In 2003 the Swiss federation of pharmacists organized a campaign "sleep disturbances--daytime sleepiness". The goal was to assist pharmacy clients in detecting likely causes of any sleep disturbance or daytime sleepiness through a free of charge screening, and to deliver targeted counselling. For pharmacy practice there are no screening or triage guidelines to assess the severity of sleep and wakefulness disturbances and potential causes for those disturbances. In this paper the outcome of the campaign in terms of feasibility, participation, observed response patterns, sale of over-the-counter (OTC) sleeping pills, and counselling activities is evaluated. METHODS: The Stanford sleep disorders questionnaire and the Epworth sleepiness scale served to identify patterns of symptoms suggestive of four major categories of sleep disorders. The questionnaires were posted on a web-site and the clients' data were entered online in the pharmacies. A report was automatically generated and immediately available online to the pharmacists. The pharmacists documented separately their counselling activities in a pharmacist's activity report. RESULTS: Six hundred and twenty-two (23%) of 2743 pharmacy clients had response patterns suggestive of obstructive sleep apnoea, 418 (15%) of restless-legs-syndrome, 39 (1%) of a sleep disorder potentially associated with a psychiatric condition and 79 (3%) of narcolepsy. An Epworth sleepiness score >10 points was found in 567 (21%). After screening, 2345 (86%) pharmacy clients received targeted counselling. Only 216 (8%) purchased an OTC sleeping pill and 704 (26%) were recommended to consult a physician, but of these, 446 (63%) were already under medical supervision. CONCLUSIONS: The online screening tool for sleep disorders and daytime sleepiness was successfully introduced in Swiss pharmacies. Pharmacies were able to assess the pattern of individual sleep disorders and to identify a possible cause in nearly one-third of the cases.

Association of lipopolysaccharide-binding protein and coronary artery disease in men

OBJECTIVES: In this study we tested the hypothesis that lipopolysaccharide-binding protein (LBP) might be able to be used as a biomarker for coronary artery disease (CAD). BACKGROUND: The mechanisms by which the innate immune recognition of pathogens could lead to atherosclerosis remain unclear. Lipopolysaccharide-binding protein is the first protein to encounter lipopolysaccharide and to deliver it to its cellular targets, toll-like receptors; therefore, its presence might be a reliable biomarker that indicates activation of innate immune responses. METHODS: A total of 247 men undergoing elective coronary angiography were studied, and the extent of coronary atherosclerosis was assessed by 2 established scores: "extent score" and "severity score." Levels of LBP, markers of inflammation, and traditional risk factors for CAD were assessed. RESULTS: Serum LBP concentration was significantly increased in 172 patients with angiographically confirmed CAD compared with 75 individuals without coronary atherosclerosis (20.6 +/- 8.7 pg/ml vs. 17.1 +/- 6.0 pg/ml, respectively; p = 0.002). Moreover in multivariable logistic regression analyses, adjusted for established cardiovascular risk factors and markers of systemic inflammation, LBP was a significant and independent predictor of prevalent CAD (p < 0.05 in all models). CONCLUSIONS: Lipopolysaccharide-binding protein might serve as a novel marker for CAD in men. The present results underlie the potential importance of innate immune mechanisms for CAD. Further studies are warranted to bolster the data and to identify pathogenetic links between innate immune system activation and atherosclerosis.

Soft-decision equalization techniques for frequency selective MIMO channels

Multi-input multi-output (MIMO) technology is an emerging solution for high data rate wireless communications. We develop soft-decision based equalization techniques for frequency selective MIMO channels in the quest for low-complexity equalizers with BER performance competitive to that of ML sequence detection. We first propose soft decision equalization (SDE), and demonstrate that decision feedback equalization (DFE) based on soft-decisions, expressed via the posterior probabilities associated with feedback symbols, is able to outperform hard-decision DFE, with a low computational cost that is polynomial in the number of symbols to be recovered, and linear in the signal constellation size. Building upon the probabilistic data association (PDA) multiuser detector, we present two new MIMO equalization solutions to handle the distinctive channel memory. With their low complexity, simple implementations, and impressive near-optimum performance offered by iterative soft-decision processing, the proposed SDE methods are attractive candidates to deliver efficient reception solutions to practical high-capacity MIMO systems. Motivated by the need for low-complexity receiver processing, we further present an alternative low-complexity soft-decision equalization approach for frequency selective MIMO communication systems. With the help of iterative processing, two detection and estimation schemes based on second-order statistics are harmoniously put together to yield a two-part receiver structure: local multiuser detection (MUD) using soft-decision Probabilistic Data Association (PDA) detection, and dynamic noise-interference tracking using Kalman filtering. The proposed Kalman-PDA detector performs local MUD within a sub-block of the received data instead of over the entire data set, to reduce the computational load. At the same time, all the inter-ference affecting the local sub-block, including both multiple access and inter-symbol interference, is properly modeled as the state vector of a linear system, and dynamically tracked by Kalman filtering. Two types of Kalman filters are designed, both of which are able to track an finite impulse response (FIR) MIMO channel of any memory length. The overall algorithms enjoy low complexity that is only polynomial in the number of information-bearing bits to be detected, regardless of the data block size. Furthermore, we introduce two optional performance-enhancing techniques: cross- layer automatic repeat request (ARQ) for uncoded systems and code-aided method for coded systems. We take Kalman-PDA as an example, and show via simulations that both techniques can render error performance that is better than Kalman-PDA alone and competitive to sphere decoding. At last, we consider the case that channel state information (CSI) is not perfectly known to the receiver, and present an iterative channel estimation algorithm. Simulations show that the performance of SDE with channel estimation approaches that of SDE with perfect CSI.

Study of water use and supply in the district of Independencia, Peru

Peru is a developing country with abundant fresh water resources, yet the lack of infrastructure leaves much of the population without access to safe water for domestic uses. The author of this report was a Peace Corps Volunteer in the sector of water & sanitation in the district of Independencia, Ica, Peru. Independencia is located in the arid coastal region of the country, receiving on average 15 mm of rain annually. The water source for this district comes from the Pisco River, originating in the Andean highlands and outflowing into the Pacific Ocean near the town of Pisco, Peru. The objectives of this report are to assess the water supply and sanitation practices, model the existing water distribution system, and make recommendations for future expansion of the distribution system in the district of Independencia, Peru. The assessment of water supply will be based on the results from community surveys done in the district of Independencia, water quality testing done by a detachment of the U.S. Navy, as well as on the results of a hydraulic model built in EPANET 2.0 to represent the distribution system. Sanitation practice assessments will be based on the surveys as well as observations from the author while living in Peru. Recommendations for system expansions will be made based on results from the EPANET model and the municipality’s technical report for the existing distribution system. Household water use and sanitation surveys were conducted with 84 families in the district revealing that upwards of 85% store their domestic water in regularly washed containers with lids. Over 80% of those surveyed are drinking water that is treated, mostly boiled. Of those surveyed, over 95% reported washing their hands and over 60% mentioned at least one critical time for hand washing when asked for specific instances. From the surveys, it was also discovered that over 80% of houses are properly disposing of excrement, in either latrines or septic tanks. There were 43 families interviewed with children five years of age or under, and just over 18% reported the child had a case of diarrhea within the last month at the time of the interview. Finally, from the surveys it was calculated that the average water use per person per day is about 22 liters. Water quality testing carried out by a detachment of the U.S. Navy revealed that the water intended for consumption in the houses surveyed was not suitable for consumption, with a median E. coli most probable number of 47/100 ml for the 61 houses sampled. The median total coliforms was 3,000 colony forming units per 100 ml. EPANET was used to simulate the water delivery system and evaluate its performance. EPANET is designed for continuous water delivery systems, assuming all pipes are always flowing full. To account for the intermittent nature of the system, multiple EPANET network models were created to simulate how water is routed to the different parts of the system throughout the day. The models were created from interviews with the water technicians and a map of the system created using handheld GPS units. The purpose is to analyze the performance of the water system that services approximately 13,276 people in the district of Independencia, Peru, as well as provide recommendations for future growth and improvement of the service level. Performance evaluation of the existing system is based on meeting 25 liters per person per day while maintaining positive pressure at all nodes in the network. The future performance is based on meeting a minimum pressure of 20 psi in the main line, as proposed by Chase (2000). The EPANET model results yield an average nodal pressure for all communities of 71 psi, with a range from 1.3 – 160 psi. Thus, if the current water delivery schedule obtained from the local municipality is followed, all communities should have sufficient pressure to deliver 25 l/p/d, with the exception of Los Rosales, which can only supply 3.25 l/p/d. However, if the line to Los Rosales were increased from one to four inches, the system could supply this community with 25 l/p/d. The district of Independencia could greatly benefit from increasing the service level to 24-hour water delivery and a minimum of 50 l/p/d, so that communities without reliable access due to insufficient pressure would become equal beneficiaries of this invaluable resource. To evaluate the feasibility of this, EPANET was used to model the system with a range of population growth rates, system lifetimes, and demands. In order to meet a minimum pressure of 20 psi in the main line, the 6-inch diameter main line must be increased and approximately two miles of trench must be excavated up to 30 feet deep. The sections of the main line that must be excavated are mile 0-1 and 1.5-2.5, and the first 3.4 miles of the main line must be increased from 6 to 16 inches, contracting to 10 inches for the remaining 5.8 miles. Doing this would allow 24-hour water delivery and provide 50 l/p/d for a range of population growth rates and system lifetimes. It is expected that improving the water delivery service would reduce the morbidity and mortality from diarrheal diseases by decreasing the recontamination of the water due to transport and household storage, as well as by maintaining continuous pressure in the system to prevent infiltration of contaminated groundwater. However, this expansion must be carefully planned so as not to affect aquatic ecosystems or other districts utilizing water from the Pisco River. It is recommended that stream gaging of the Pisco River and precipitation monitoring of the surrounding watershed is initiated in order to begin a hydrological study that would be integrated into the district’s water resource planning. It is also recommended that the district begin routine water quality testing, with the results available to the public.

DESIGN AND SYNTHESIS OF MULTIFUNCTIONAL POLYMERIC MICELLES FOR GENE-DIRECTED ENZYME PRODRUG THERAPY

Gene-directed enzyme prodrug therapy is a form of cancer therapy in which delivery of a gene that encodes an enzyme is able to convert a prodrug, a pharmacologically inactive molecule, into a potent cytotoxin. Currently delivery of gene and prodrug is a two-step process. Here, we propose a one-step method using polymer nanocarriers to deliver prodrug, gene and cytotoxic drug simultaneously to malignant cells. Prodrugs acyclovir, ganciclovir and 5-doxifluridine were used to directly to initiate ring-opening polymerization of epsilon-caprolactone, forming a hydrophobic prodrug-tagged poly(epsilon-caprolactone) which was further grafted with hydrophilic polymers (methoxy poly(ethylene glycol), chitosan or polyethylenemine) to form amphiphilic copolymers for micelle formation. Successful synthesis of copolymers and micelle formation was confirmed by standard analytical means. Conversion of prodrugs to their cytotoxic forms was analyzed by both two-step and one-step means i.e. by first delivering gene plasmid into cell line HT29 and then challenging the cells with the prodrug-tagged micelle carriers and secondly by complexing gene plasmid onto micelle nanocarriers and delivery gene and prodrug simultaneously to parental HT29 cells. Anticancer effectiveness of prodrug-tagged micelles was further enhanced by encapsulating chemotherapy drugs doxorubicin or SN-38. Viability of colon cancer cell line HT29 was significantly reduced. Furthermore, in an effort to develop a stealth and targeted carrier, CD47-streptavidin fusion protein was attached onto the micelle surface utilizing biotin-streptavidin affinity. CD47, a marker of self on the red blood cell surface, was used for its antiphagocytic efficacy, results showed that micelles bound with CD47 showed antiphagocytic efficacy when exposed to J774A.1 macrophages. Since CD47 is not only an antiphagocytic ligand but also an integrin associated protein, it was used to target integrin alpha(v)beta(3), which is overexpressed on tumor-activated neovascular endothelial cells. Results showed that CD47-tagged micelles had enhanced uptake when treated to PC3 cells which have high expression of alpha(v)beta(3). The synthesized multifunctional polymeric micelle carriers developed could offer a new platform for an innovative cancer therapy regime.

Two-Phase Flow In Microchannels: Morphology And Interface Phenomena

The existence and morphology, as well as the dynamics of micro-scale gas-liquid interfaces is investigated numerically and experimentally. These studies can be used to assess liquid management issues in microsystems such as PEMFC gas flow channels, and are meant to open new research perspectives in two-phase flow, particularly in film deposition on non-wetting surfaces. For example the critical plug volume data can be used to deliver desired length plugs, or to determine the plug formation frequency. The dynamics of gas-liquid interfaces, of interest for applications involving small passages (e.g. heat exchangers, phase separators and filtration systems), was investigated using high-speed microscopy - a method that also proved useful for the study of film deposition processes. The existence limit for a liquid plug forming in a mixed wetting channel is determined by numerical simulations using Surface Evolver. The plug model simulate actual conditions in the gas flow channels of PEM fuel cells, the wetting of the gas diffusion layer (GDL) side of the channel being different from the wetting of the bipolar plate walls. The minimum plug volume, denoted as critical volume is computed for a series of GDL and bipolar plate wetting properties. Critical volume data is meant to assist in the water management of PEMFC, when corroborated with experimental data. The effect of cross section geometry is assessed by computing the critical volume in square and trapezoidal channels. Droplet simulations show that water can be passively removed from the GDL surface towards the bipolar plate if we take advantage on differing wetting properties between the two surfaces, to possibly avoid the gas transport blockage through the GDL. High speed microscopy was employed in two-phase and film deposition experiments with water in round and square capillary tubes. Periodic interface destabilization was observed and the existence of compression waves in the gas phase is discussed by taking into consideration a naturally occurring convergent-divergent nozzle formed by the flowing liquid phase. The effect of channel geometry and wetting properties was investigated through two-phase water-air flow in square and round microchannels, having three static contact angles of 20, 80 and 105 degrees. Four different flow regimes are observed for a fixed flow rate, this being thought to be caused by the wetting behavior of liquid flowing in the corners as well as the liquid film stability. Film deposition experiments in wetting and non-wetting round microchannels show that a thicker film is deposited for wetting conditions departing from the ideal 0 degrees contact angle. A film thickness dependence with the contact angle theta as well as the Capillary number, in the form h_R ~ Ca^(2/3)/ cos(theta) is inferred from scaling arguments, for contact angles smaller than 36 degrees. Non-wetting film deposition experiments reveal that a film significantly thicker than the wetting Bretherton film is deposited. A hydraulic jump occurs if critical conditions are met, as given by a proposed nondimensional parameter similar to the Froude number. Film thickness correlations are also found by matching the measured and the proposed velocity derived in the shock theory. The surface wetting as well as the presence of the shock cause morphological changes in the Taylor bubble flow.

The laulimalide family: total synthesis and biological evaluation of neolaulimalide, isolaulimalide, laulimalide and a nonnatural analogue

We herein describe in full detail the first total synthesis of the antitumor agents neolaulimalide and isolaulimalide as well as a highly efficient route to laulimalide. A Kulinkovich reaction followed by a cyclopropyl-allyl rearrangement is used to install the exo-methylene group. The C(2)-C(16) aldehyde fragment is coupled with the C(17)-C(28) sulfone fragments by a highly (E)-selective Julia-Lythgoe-Kocienski olefination to deliver the key intermediates of all three syntheses. Various conditions for the Yamaguchi macrolactonization are applied to close the individual macrocycles. Finally a carefully elaborated endgame was developed to solve the problem of acyl migration in the case of neolaulimalide. All compounds were tested against several cell lines. The cytotoxicity of neolaulimalide could be confirmed for the first time since its original isolation and it could be shown that it induces tubulin polymerization as efficiently as laulimalide.

Social Work in an Ethnically Diverse Europe: The Shifting Challenges of Difference

This article addresses the inherently politicised context of social work practice located within the contested logics and values of national social policy and professional values and identities. Noting the key role of social work in delivering the state’s promise of social citizenship, it is argued that the increasing neo-nationalist sentiments and politics in European states generate significant pressures upon the universalist, inclusive, values of social work in a multiethnic Europe. The academic and policy debate around social cohesion is explored to illustrate how an assimilationist drift in multicultural state policies undermines the capacity of social work services to deliver appropriate, ethnically sensitive, services. It is further argued that the pervasive spread of populist counter-narratives to multiculturalism erode support for anti-racist and transcultural social work practice. In this context it is argued that social work must acknowledge its compromised situation and explicitly develop a political agenda committed to guaranteeing substantive equality in service delivery.

Factors influencing the quality of the consultation process

Sport psychology services have become to be an important brick stone when building athletic success. The strive for better performance is not only a characteristic of athletes, but of the whole support system in top level sport including sport psychology. Sport psychology consultants are permanently challenged to deliver highest quality services to their clients if they do not want to lose their contracts. Sport psychologists are continuously improving their consulting skills, learn new intervention techniques, read scientific papers and, last but not least, gain experience by accumulating hours of deliberate practice (Ericsson) in sport psychology. Even with increasing experience, the consultant has a certain number of degrees of freedom and has to make a series of decisions about how he or she wants to work. Quality, however, depends on a number of issues, and not all of them are under direct control of the consultant. It is argued that, in order for these choices being good, the following factors - among others - must be considered: Who is seeking assistance? What are the "issues and problems" (Gardner & Moore, 2006) the athlete is confronted with? What kind of approaches do fit with the client's need? Who is the 'client' the sport psychologist is supposed to work with? If it is a team, is the sport psychologist supposed to work with a number of individuals, with the coach, or with the whole system? Where are the boundaries of the system? What is the role of the sport psychologist in the sport system? All these issues directly affect the process and outcome quality of the sport psychology consultant. A sound theoretical basis, in connection with a distinct philosophy of the intervention, is an important cornerstone for the quality of sport psychology consultation.

The Advantages of Parametric Modeling for the Reconstruction of Historic Buildings

Consecrated in 1297 as the monastery church of the four years earlier founded St. Catherine’s monastery, the Gothic Church of St. Catherine was largely destroyed in a devastating bombing raid on January 2nd 1945. To counteract the process of disintegration, the departments of geo-information and lower monument protection authority of the City of Nuremburg decided to getting done a three dimensional building model of the Church of St. Catherine’s. A heterogeneous set of data was used for preparation of a parametric architectural model. In effect the modeling of historic buildings can profit from the so called BIM method (Building Information Modeling), as the necessary structuring of the basic data renders it into very sustainable information. The resulting model is perfectly suited to deliver a vivid impression of the interior and exterior of this former mendicant orders’ church to present observers.

The transpedicular approach as an alternative route for intervertebral disc regeneration

STUDY DESIGN Descriptive anatomical study on ovine and human cadaveric lumbar spinal segments. OBJECTIVE To describe the alternative transpedicular approach to deliver therapeutic agents into intervertebral disc (IVD). SUMMARY OF BACKGROUND DATA The present delivery approach of therapeutic agents (growth factors/cells/hydrogels) within the IVD is through injection, via the annulus fibrosus (AF). However, it has recently been demonstrated that small needle puncture of the AF leads to further degeneration and disc herniation. In addition, the injected material has a high chance to be extruded through the AF injury. METHODS Lumbar ovine and human spinal segments were used. Under fluoroscopy, a 2-mm Kirschner wire was introduced in the caudal vertebra through the pedicle and the inferior endplate to the nucleus pulposus. Gross anatomy analysis and high-resolution peripheral quantitative computed tomography (HR-pQCT) were performed to assess the right position of the wire in pedicles. Discography and nucleotomy were performed using a 14G cannula insertion or a 2-mm arthroscopic shaver blade, respectively. Nucleoplasty was also performed with agarose gel/contrast agent and imaged with HR-pQCT. RESULTS Gross anatomy, fluoroscopy, and HR-pQCT images showed that the nucleus pulposus could be approached through the endplate via the pedicle without affecting the spinal canal and the neural foramina. The contrast agent was delivered into the IVD and nucleus pulposus was removed from the disc and filled with agarose gel. CONCLUSION This study describes how a transpedicular approach can be used as an alternative route to deliver therapeutic agents to the disc without disruption of the AF showing the potential use of this technique in preclinical research and highlighting its clinical relevance for IVD regeneration.

Comparison of clinical knowledge management capabilities of commercially-available and leading internally-developed electronic health records.

BACKGROUND: We have carried out an extensive qualitative research program focused on the barriers and facilitators to successful adoption and use of various features of advanced, state-of-the-art electronic health records (EHRs) within large, academic, teaching facilities with long-standing EHR research and development programs. We have recently begun investigating smaller, community hospitals and out-patient clinics that rely on commercially-available EHRs. We sought to assess whether the current generation of commercially-available EHRs are capable of providing the clinical knowledge management features, functions, tools, and techniques required to deliver and maintain the clinical decision support (CDS) interventions required to support the recently defined "meaningful use" criteria. METHODS: We developed and fielded a 17-question survey to representatives from nine commercially available EHR vendors and four leading internally developed EHRs. The first part of the survey asked basic questions about the vendor's EHR. The second part asked specifically about the CDS-related system tools and capabilities that each vendor provides. The final section asked about clinical content. RESULTS: All of the vendors and institutions have multiple modules capable of providing clinical decision support interventions to clinicians. The majority of the systems were capable of performing almost all of the key knowledge management functions we identified. CONCLUSION: If these well-designed commercially-available systems are coupled with the other key socio-technical concepts required for safe and effective EHR implementation and use, and organizations have access to implementable clinical knowledge, we expect that the transformation of the healthcare enterprise that so many have predicted, is achievable using commercially-available, state-of-the-art EHRs.