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Commercial specifications for a new biotherapeutic product are a critical component of the product's overall control strategy that ensures safety and efficacy. This paper describes strategies for setting commercial specifications as proposed by a consortium of industry development scientists. The specifications for some attributes are guided by compendia and regulatory guidance. For other product quality attributes (PQAs), product knowledge and the understanding of attribute criticality built throughout product development should drive specification setting. The foundation of PQA knowledge is an understanding of potential patient impact through an assessment of potency, PK, immunogenicity and safety. In addition to PQA knowledge, the ability of the manufacturing process to consistently meet specifications, typically assessed through statistical analyses, is an important consideration in the specification-setting process. Setting acceptance criteria that are unnecessarily narrow can impact the ability to supply product or prohibit consideration of future convenient dosage forms. Patient-centric specifications enable appropriate control over higher risk PQAs to ensure product quality for the patient, and flexibility for lower risk PQAs for a sustainable supply chain. This paper captures common strategic approaches for setting specifications for standard biotherapeutic products such as monoclonal antibodies and includes considerations for ensuring specifications are patient centric.

Background: Homograft tissue is an important reconstructive material used in the surgical correction of a variety of congenital heart defects. The aim of this study is to evaluate the long-term outcome of pulmonary artery (PA) branch patches used in the reconstruction of the thoracic aorta in children. Methods: Retrospective review of 124 consecutive pediatric patients undergoing corrective surgery for their congenital heart defects between 2001 and 2016. Survival, reoperation, and reintervention data were collected, as well as imaging data to assess for presence of recoarctation, dilation, or aneurysm formation in the area of patch reconstruction. Results: Overall 15-year survival was 83.9% and 15-year freedom from reintervention in the area of patch reconstruction was 89.2%. Rates of mortality (0%), cardiac transplantation (0%), and reoperation (0.8%) attributable to the area of patch reconstruction were low. The frequency of catheter-based intervention in the area of patch reconstruction was 9.7%; such interventions were successful in all but one patient, who ultimately underwent successful surgical aortoplasty. Conclusions: Homograft patches harvested from PA branches are an effective reconstructive material used for reconstruction of the aorta in small children. Long-term results show no risk of aneurysm formation and low rates of stenosis formation.

Purpose of reviewThis is a review of the research on the effectiveness of vitamin supplementation for alcoholism and alcohol-related illnesses. The focus is on research, both clinical and basic on alcohol treatment and nutritional effectiveness of these vital nutrients.Recent findingsMost of the res

In this paper we address the problem of selection bias under multiple testing in the context of investment strategies. We introduce an unsupervised learning algorithm that determines the number of ...

Post-translational modifications (PTMs) that impact the safety or efficacy of protein therapeutics are critical quality attributes (CQAs) that need to be controlled to ensure product quality. Peptide mapping with online mass spectrometry (MS) is a powerful tool that has been used for many years to monitor PTM CQAs during product development. However, operating peptide mapping methods with high-resolution mass spectrometers in GMP compliant, commercial quality control (QC) labs can be difficult. Peptide mapping is also required as an identity test in several countries. To address these two different needs, we utilized high-resolution peptide mapping for comprehensive characterization during development and then developed and validated a targeted multi-attribute monitoring (MAM) method using the low-resolution Waters QDa MS system with a fully automated data processing workflow that is suitable for identity (ID) testing, sequence variant control, and CQA quantitation in commercial QC labs. The ID-MAM method was validated for the quantitation of three selected PTM CQAs (CDR isomerization, Fc Met oxidation, and CDR Met oxidation) to ensure control of the oxidation and isomerization degradation pathways of a bispecific antibody (BsAb). This ID-MAM method was successfully validated in six labs (three analytical development and three QC labs) across four countries for commercial release and stability testing of a BsAb. CQA results obtained with the ID-MAM method were similar to results obtained using high-resolution peptide mapping, and the method was robust and reproducible. To our knowledge, this ID-MAM method is the first MS-based peptide mapping method implemented in GMP compliant QC labs for commercial release and stability testing of a biotherapeutic.

Aquafeed manufacturers are increasingly interested in ensuring consistently high-quality products, while relying heavily on poultry offal meal (POM), which is inevitably variable. This study examined the chemical composition of 22 different commercially and experimentally produced POM to determine which chemical variables best predict in vivo protein digestibility in Atlantic salmon (Salmo salar) and to evaluate which production variable, rendering temperature or raw material freshness, has a greater impact on digestibility. The chemical composition of commercially and experimentally produced POM was extremely variable. Significant relationships were found between in vivo dietary protein digestibility and D-glutamic acid (R2 = 0.64) and D-aspartic acid (R2 = 0.62). Rendering temperature and raw material freshness had significant effects on D-amino acids and biogenic amines. D-glutamic and D-aspartic acids may provide rapid-assessment indication of POM quality, as these D-amino acids were linked to protein digestibility and affected by the production variables. This study supports the well-held notion that POM is subject to significant variability and addresses the specific chemical characterisation of POM and the production conditions which impact nutrient digestibility in Atlantic salmon. These results prove beneficial to aquafeed manufactures aiming to ensure consistency and high nutritional quality in protein sources for aquafeed.

Liquid chromatography–mass spectrometry (LC–MS) has been widely used throughout biotherapeutic development. However, its implementation in GMP-compliant commercial quality control (QC) laboratories remains a challenge. In this publication, we describe the covalidation and implementation of an automated, high-throughput, and GMP compliant subunit LC–MS method for monitoring antibody oxidation for commercial product release and stability testing. To our knowledge, this is the first report describing the implementation of a high-resolution LC–MS method in commercial QC laboratories for product release and stability testing in the biopharmaceutical industry. This work paves the road for implementing additional LC–MS methods to modernize testing in commercial QC with more targeted control of product quality.

Part two of this review evaluates the impact of physiological, husbandry and seasonal factors on the physicochemical properties of raw bovine milk and on products manufactured from it. For producers of dairy products, there are opportunities to select the most appropriate feeding regimes for producing raw milk which is optimal for their products, as well as understanding what are the best products to be made from milk produced at different times of the year. For these reasons, the concept of ‘best use’ for milk will become an exciting and profitable area for study.

This article reviews the literature underpinning the concept of ‘best use’ for milk. In factories where more than one milk product type is manufactured, there is an opportunity to select milk that would be best suited to that product. Also, for those considering producer processing, there is an opportunity to select the most appropriate breed of cow to produce milk, which is optimal for their selected products. It is the aim of this article to provide a better understanding of the genetic factors that influence the properties of raw milk and processed milk products in order to make best use for milk a more viable proposition.

The levels of many product related variants observed during the production of monoclonal antibodies are dependent on control of the manufacturing process, especially the cell culture process. However, it is difficult to characterize samples pulled from the bioreactor due to the low levels of product during the early stages of the process and the high levels of interfering reagents. Furthermore, analytical results are often not available for several days, which slows the process development cycle and prevents "real time" adjustments to the manufacturing process. To reduce the delay and enhance our ability to achieve quality targets, we have developed a low-volume, high-throughput, and high-content analytical platform for at-line product quality analysis. This workflow includes an automated, 96-well plate protein A purification step to isolate antibody product from the cell culture fermentation broth, followed by rapid, multiattribute LC-MS analysis. We have demonstrated quantitative correlations between particular process parameters with the levels of glycosylated and glycated species in a series of small scale experiments, but the platform could be used to monitor other attributes and applied across the biopharmaceutical industry.

The environment of a balloon based telescope puts opto-mechanical stability demands that wavefront sensing and focus control are important features to consider. The GHAPS telescope is designed to correct for rigid body motion of the secondary mirror based upon wavefront sensing from reference stars. In order to support the concept of operations of this approach, the precision of wavefront sensing with candidate reference stars needs to be addressed. Precision is expected to degrade with reduction in irradiance. To confirm this, a study was conducted to determine the relationship between broadband and narrow spectral irradiance and wavefront measurement precision. The results of the study demonstrate that a precision of 5 nm RMS can be achieved with a 20 x 20 sampling of the wavefront with an irradiance of a visual magnitude 5 star on 1 meter aperture with an exposure of 30 msec.

Most investment strategies uncovered by practitioners and academics are false. This partially explains the high rate of failure, especially among quantitative hedge funds (smart beta, factor investing, stat-arb, CTAs, etc.) In this paper we examine why false positives are so prevalent in finance, why researchers fail (in many cases purposely) to detect them, and why firms are able to monetize their scheme. Beyond merely pointing to this industrywide problem, we offer a practical solution. We hope that the machine learning tools presented in this paper will help financial academic journals filter out false positives, and bring up the retraction rate to reasonable levels. The SEC, FINRA and other regulatory agencies worldwide could use these tools to take a more active role in curving this rampant financial fraud. A presentation based on this paper can be found at https://ssrn.com/abstract=3173146.

As many scholars have noted, Samuel Butler's The Way of All Flesh is preoccupied with the authenticity of genealogical records. Through epithets, letters, newspapers, and its own meta-role as manus...

Energy consumption, water utilisation and waste production are now important environmental issues. However, compilations of data are not readily available, making it difficult for companies to assess how they are performing. This review aims to summarise the data that are available, including some benchmarking values. Also discussed are techniques for reducing water and energy consumption and waste production, tools for monitoring this and assistance that is available to improve efficiency ratios and reduce costs associated with these issues. Using information in this review, an individual company should be able to compare its performance against others producing similar products, nationally or globally in order to set and maintain rational benchmarking values to improve its performance and deal with environmental concerns.

The growing use of ‘targeted profiling’ approaches for the deconvolution of 1D-1H-NMR spectra by comparison to a pure compound library has created a need for an in-depth characterization of quantification variability that is beyond what is currently available in the literature. In this study, we explore the underlying source of quantification variability (tube insertion, spectra acquisition, and profiling) as well as a number of other factors, such as temporal consistency of repeated NMR scans, human consistency in repeated profiles, and human versus machine sampling. We also look at the effect of different pulse sequences on the differences between acquired spectra and the peak reference library. Two sample types were considered for this work—a synthetic five compound mixture as well as human urine. The result is a comprehensive examination of 1D-1H-NMR quantification error. Our investigation into variability sources revealed that apart from profiling, sample insertion and/or shimming can play a significant role in final quantification, a finding that is equally applicable to all integration-based methods of quantification. Both sources of error were also found to have temporal relationships, with bias identified as a function of both scan and profiling order, reinforcing the need for randomization in scanning and profiling. As well as presenting a practical estimate of variability in human urine samples, we have uncovered a considerable amount of complexity in underlying NMR variability that will hopefully serve as impetus for future exploration in this area.

Cloud infrastructures increasingly include a heterogeneous mix of components in terms of performance, power, and energy usage. As the size of cloud infrastructures grows, power consumption becomes a significant constraint. We use Apache Mesos and Apache Aurora, which provide massive scalability to web-scale applications, to demonstrate how a policy driven approach involving bin-packing workloads according to their power profiles, instead of the default allocation by Mesos and Aurora, can effectively reduce the peak-power and energy usage as well as the node utilization, when workloads are co-scheduled. Our experimental results show reductions of 11% in peak power, 86% for total energy usage, and an increase in utilization of 148% for memory and 8% CPU for the different policies.

Scheduling in large scale dynamic grids comprising eclectic collections of resources is increasingly difficult. Autonomous resource neighborhoods may wish to determine the level of grid offered load that they can or will accept; different sites may wish to attract different amounts of load, to satisfy some desired property within a grid economy. This changes the traditional notion of load sharing, which generally assumes that the desired equilibrium should be an equal distribution of load across all participating machines, because they are under the jurisdiction of a single site, and therefore more likely to implement one common policy. In large-scale grids, nodes and neighborhoods should instead get a portion of the load that best matches their local policies for supporting and admitting grid jobs. This article describes information dissemination protocols that can distribute load in this way, without using load rebalancing through job migration, which is more difficult and costly in large-scale heterogeneous grids. Essentially, nodes adjust their advertising rates and aggressiveness to influence where jobs get scheduled. We report experimental results with example resource configurations in which each resource neighborhood determines its ideal grid load and disseminates accordingly. In turn, each neighborhood attracts the requisite amount of resource requests from the grid. Moreover, performance does not degrade: overall query satisfaction rates are within 9% of both adaptive dissemination protocols that use static adaptation policies, and static dissemination protocols that may be custom-tailored to specific resource and load distributions.

When the call went out, about a generation ago, that the Western canon must be purged of its surfeit of "dead white males," the cry was loudest in departments of English. (Why this should be so--why it is easier to rally a mob against Milton and Spenser, say, than Michelangelo and Mozart--has never been satisfactorily explained.) And it is more than ironic that that same canon has in the intervening years been expanded to include someone who might be regarded as the double-distilled quintessence of the dead white male--that arch-brutalizer of women, Alfred Hitchcock--and that this should happen precisely in departments of English. In recent years, Hitchcock has been the subject of seminars and surveys throughout the country, almost all of them offered by English departments. A small selection might include "Theories of Authorship in the Cinema: Alfred Hitchcock" (Bryn Mawr); "Hitchcock: Cinema, Gender, Ideology" (Tufts); "Hitchcock in England and America" (Vanderbilt); "The Cinema of Alfre... Language: en

Background: To address the need of caring for the growing number of patients with diabetes, East Carolina University implemented a 1-year fellowship in diabetes. Most of the region has been designated as Health Professional Shortage Areas. Description: The objective of the fellowship is to educate primary care physicians to serve as regional specialists in diabetes. The program is administered by physicians, educators, and representatives of the university's affiliated teaching hospital. The curriculum includes clinical, didactic, and experiential learning strategies in outpatient and inpatient settings. Adult and pediatric endocrinologists, obstetricians, and generalists mentor and evaluate the fellows. Evaluation: This innovative training program has improved the availability of high-quality diabetes care for underserved patients in the region. Mean glycemic control in fellows' patients improved and other clinical endpoints were also met. Conclusions: A 1-year diabetes fellowship is a replicable solutio...

Grid resource providers can use gossiping to disseminate their available resource state to remote regions of the grid to attract application load. Pairwise gossiping protocols exchange information about limited subsets of other resources between pairs of potentially remote participants. In epidemic gossiping protocols, the provider disseminates information to multiple neighbors, who in turn forward it to their neighbors, and so on. One important metric for these protocols is their coverage, which characterizes how many and which resources receive the information. Coverage characteristics of epidemic protocols are non-uniform, concentrated within the vicinity of a disseminating node; they can exhibit bi-modal behavior where information either reaches distant nodes or dies out quickly. Pairwise gossiping protocols, on the other hand, provide a more uniform coverage, but it can take longer for the dissemination to reach desired uniformity. In this paper, we study performance characteristics of three gossiping protocols: (1) epidemic gossiping, (2) pairwise gossiping, and (3) adaptive information dissemination (which is based on a form of epidemic gossiping). We report experimental results based on our simulation framework that compare the three protocols in terms of packet overhead and query satisfaction rates. We show that pairwise gossiping protocols work best when resource distribution on the grid is uniform, and that they can be configured to perform well in support of grid scheduling. We also verify this behavior under typical node failures of real-world production grids.

Tetralogy of Fallot associated with complete atrioventricular canal (TC) is a relatively rare form of conotruncal anomaly. The indications for a systemico-pulmonary shunt are few today. We favor a two patch technique. Most of the time, the VSD patch closure is performed through the right atrium only; however a ventriculotomy is used when needed.

The Common Component Architecture (CCA) provides a means for software developers to manage the complexity of large-scale scientific simulations and to move toward a plug-and-play environment for high-performance coputing. In the scientific computing context, component models also promote collaboration using independently developed software, thereby allowing particular individals or groups to focus on the aspects of greatest interest to them. The CCA supports parallel and distributed coputing as well as local high-performance connections between components in a language-independent manner. The design places minimal requirements on components and thus facilitates the integration of existing code into the CCA environment. The CCA model imposes minimal ovehead to minimize the impact on application performance. The focus on high performance distinguishes the CCA from most other component models. The CCA is being applied within an increasing range of disciplines, including cobustion research, global climate simulation, and computtional chemistry.

Patent ductus arteriosus (PDA) is a recognized risk factor for massive pulmonary hemorrhage (MPH) in the newborn and is generally seen in association with other MPH risk factors such as prematurity. We report 6 cases of sudden and unexpected death of infants older than 4 days with MPH and PDA at autopsy. The cases were reviewed for other factors that could contribute to MPH to ascertain whether PDA is directly linked to MPH. Histology samples were examined for distribution of hemorrhage in the lungs and iron stained for hemosiderin evaluation. All of the cases had clinical histories and scene examinations which raised the differential diagnosis of mechanical asphyxia in the form of so-called overlayings. The diagnostic dilemma of attributing the MPH to the PDA as the sole cause, dual cause, or incidental finding is discussed. These cases illustrate the medicolegal dilemma faced by the pathologist, as well as the need for further research into the potential association of PDA with MPH.

This case study describes the area health education centers (AHEC) program in West Virginia, spanning 30 years from a first-generation project at Charleston in 1972 (AHEC 1) to a newly funded statewide program (AHEC 2). The outcome is an evolving university-community partnership designed to meet changing work-force and community health needs in the heart of rural Appalachia. West Virginia University's (WVU's) application of the original Carnegie Commission AHEC recommendations (1970) resulted in the Charleston AHEC, now part of the Robert C. Byrd Health Sciences Center of WVU. AHEC today trains more than 135 residents and interns, and one-third of the third-year and fourth-year WVU medical students. Charleston offers clinical and continuing education for nurses, dentists, pharmacists, and allied health professionals. A health sciences library, distance learning, and a network of primary care clinics help define Charleston's unique AHEC role. This AHEC hub continues to meet the classic Carnegie goals of recruiting and retaining health professionals, and providing access to care in the original service area and statewide. Based on the Charleston experience, four new federally funded AHECs are being developed to link rural primary care residencies with the state-funded West Virginia rural health education partnerships. These rural consortia AHECs are applying the concept of community competency, a performance-based methodology, to integrate learning while achieving the goals of Healthy People 2010.

Grid computing is the use of large collections of heterogeneous, distributed resources (including machines, databases, devices, and users) to support large-scale computations and wide-area data access. The Legion system is an implementation of a software architecture for grid computing. The basic philosophy underlying this architecture is the presentation of all grid resources as components of a single, seamless, virtual machine. Legion's architecture was designed to address the challenges of using and managing wide-area resources. Features of the architecture include: global, shared namespaces; support for heterogeneity; security; wide-area data sharing; wide-area parallel processing; application-adjustable fault tolerance; efficient scheduling and comprehensive resource management. We present the core design of the Legion architecture, with focus on the critical issues of extensibility and site autonomy. Grid systems software must be extensible because no static set of system-level decisions can meet all of the diverse, often conflicting, requirements of present and future user communities, nor take best advantage of unanticipated future hardware advances. Grid systems software must also support complete site autonomy, as resource owners will not turn control of their resources over to a dictatorial system.

When data centers employ the common and economical practice of upgrading subsets of nodes incrementally, rather than replacing or upgrading all nodes at once, they end up with clusters whose nodes have non-uniform processing capability, which we also call performance-heterogeneity. Popular frameworks supporting the effective MapReduce programming model for Big Data applications do not flexibly adapt to these environments. Instead, existing MapReduce frameworks, including Hadoop, typically divide data evenly among worker nodes, thereby inducing the well-known problem of stragglers on slower nodes. Our alternative MapReduce framework, called MARLA, divides each worker’s labor into sub-tasks, delays the binding of data to worker processes, and thereby enables applications to run faster in performance-heterogeneous environments. This approach does introduce overhead, however. We explore and characterize the opportunity for performance gains, and identify when the benefits outweigh the costs. Our results suggest that frameworks should support finer grained sub-tasking and dynamic data partitioning when running on some performance-heterogeneous clusters. Blindly taking this approach in homogeneous clusters can slow applications down. Our study further suggests the opportunity for cluster managers to build performance-heterogeneous clusters by design, if they also run MapReduce frameworks that can exploit them.

When data centers employ the common and economical practice of upgrading subsets of nodes incrementally, rather than replacing or upgrading all nodes at once, they end up with clusters whose nodes have non-uniform processing capability, which we also call performance-heterogeneity. Popular frameworks supporting the effective MapReduce programming model for Big Data applications do not flexibly adapt to these environments. Instead, existing MapReduce frameworks, including Hadoop, typically divide data evenly among worker nodes, thereby inducing the well-known problem of stragglers on slower nodes. Our alternative MapReduce framework, called MARLA, divides each worker's labor into sub-tasks, delays the binding of data to worker processes, and thereby enables applications to run faster in performance-heterogeneous environments. This approach does introduce overhead, however. We explore and characterize the opportunity for performance gains, and identify when the benefits outweigh the costs. Our results suggest that frameworks should support finer grained sub-tasking and dynamic data partitioning when running on some performance-heterogeneous clusters. Blindly taking this approach in homogeneous clusters can slow applications down. Our study further suggests the opportunity for cluster managers to build performance-heterogeneous clusters by design, if they also run MapReduce frameworks that can exploit them.

Although it has been shown with other drugs of abuse, behavioral sensitization has not been shown with ethanol in rats. One possible reason for the negative previous findings may be due to the doses of ethanol employed in the different phases of sensitization. In the current experiment, outbred Sprague-Dawley rats were divided into either high or low responders to novelty. They were pretreated for 15 days with intraperitoneal injections of either saline or 1.0 g/kg ethanol, and then given a challenge dose of 0.25 g/kg ethanol after a 3-week period. During the first 10 min after the challenge dose, rats high in response to novelty pretreated with ethanol displayed higher locomotor activity scores relative to the other three groups. These data demonstrated evidence for behavioral sensitization with ethanol in outbred rats.

Milk was subjected to a combination process involving reduced heat treatment (RHT) of 117 degrees C for 2 s and nisin (75 and 150 IU ml(-1)). The microbial activity and other quality aspects were compared with a RHT control (without nisin) and with a ultrahigh temperature (UHT) milk processed at 142 degrees C for 2 s. Nisin was found to inhibit microbial growth for products stored without refrigeration, and RHT-nisin samples stored at 30 degrees C showed very low spoilage rates during 150 days, although not low enough to satisfy requirements for commercial sterility. RHT-nisin samples could be distinguished from and were preferred to the UHT control. Significant browning occurred during storage at 30 degrees C and above but was less in the RHT-nisin milk samples compared with the UHT milk. In RHT-nisin milk samples stored at 20 and 10 degrees C, no microbial activity could be detected in most samples after storage for 1 year. The effectiveness of this combination of RHT, nisin, and low storage temperatures against gram-positive spore-forming bacteria suggests potential for use of nisin in extended shelf life products.

Soymilk is a traditional drink of Chinese origin. Recently a calcium-fortified soymilk (CFSM) has been developed as a functional beverage. The consumption of soy protein is claimed to result in a lower risk of some chronic diseases (including cardiovascular disease, cancer and osteoporosis) and alleviation of menopausal symptoms. Thus, CFSM has been consumed increasingly by European and North American consumers, with a large growth in sales.

During the 2011 Desert Research and Technology Studies (D-RATS) field tests, NASA and Honeywell conducted a series of special standalone demonstrations of two different heads up display technologies that are being considered for incorporation into the next generation spacesuit. These were conducted in anticipation of the need to provide a robust informational system that will facilitate increased crewmember autonomy by providing them an expanded set of information through visual and other means. This information includes but is not limited to life support system status information, navigational instructions, emergency alarms, and procedures. The two technologies tested were quite distinct from one another. One was a see-through display using a sophisticated waveguide and laser light source, and the other was a direct view, fully occluded display using more conventional LCD display technology. Since no spacesuits were used during these demonstrations, both displays were packaged in head worn goggles. Quantitative and qualitative data relating to perceived resolution and contrast was collected and analyzed for each device. Evaluations of the hardware started with notional status displays used during walkarounds, and were followed with performance of procedures that used Apollo heritage mockup hardware. A viewfinder function was also evaluated for each device. Questionnaires were administered to capture user opinions and perceived workload. The testing yielded numerous specific findings and increased confidence that heads up display technology will be appropriate in the future spacesuit. While both devices successfully delivered information to the users, and there was no obvious consensus as to which display type was preferred, the recommendation is that near-term future development testing focus on a see-through solution. This is due to the belief that see-through displays have many advantages, while their shortcomings can be overcome through future design enhancements.

A major disadvantage of rural medical practice is the limited reserve of consultative options. To determine the perceived clinical utility and educational impact of the West Virginia University Medical Access and Referral System (MARS), a 24-hour prompt telephone-consultation service, a mailed questionnaire was administered to 303 West Virginia clinicians who had used MARS for infectious disease problems. The overall questionnaire response rate was 62 percent. Callers included family practitioners (35%), medical specialists (32%), surgical specialists (13%), pediatricians (11%), obstetricians (5%), and nonphysicians (4%). Major referral questions posed were therapeutic (60%), diagnostic (48%), and epidemiologic (10%) in nature. On a scale of 1 (not useful) to 5 (very useful), survey responders rated the overall clinical usefulness of MARS as either a 4 (22%) or 5 (76%). Callers felt that MARS consultation assisted in accurate case diagnosis in 80 percent of cases, and aided in successful therapeutic management of 96 percent of cases. An educational benefit was reported by 96 percent of responders. Physicians located in more rural, underserved areas tended to use MARS to a greater degree than colleagues in more populated, medically accessible areas (P

Grid resource providers can use gossiping to disseminate their available resource state to remote regions of the grid to attract application load. Pairwise gossiping protocols exchange information about limited subsets of other resources between pairs of potentially remote participants. In epidemic gossiping protocols, the provider disseminates information to multiple neighbors, who in turn forward it to their neighbors, and so on. One important metric for these protocols is their coverage, which characterizes how many and which resources receive the information. Coverage characteristics of epidemic protocols are non-uniform, concentrated within the vicinity of a disseminating node; they can exhibit bi-modal behavior where information either reaches distant nodes or dies out quickly. Pairwise gossiping protocols, on the other hand, provide a more uniform coverage, but it can take longer for the dissemination to reach desired uniformity. In this paper, we study performance characteristics of three gossiping protocols: (1) epidemic gossiping, (2) pairwise gossiping, and (3) adaptive information dissemination (which is based on a form of epidemic gossiping). We report experimental results based on our simulation framework that compare the three protocols in terms of packet overhead and query satisfaction rates. We show that pairwise gossiping protocols work best when resource distribution on the grid is uniform, but that they can be configured to perform well in support of grid scheduling.

Resource scheduling in large-scale, volatile desktop grids is challenging because resource state is both dynamic and eclectic. Matching available resources with requests is not always possible with existing approaches. Partial dissemination protocols, such as gossiping, may provide efficient schedules when resource requesters are located near providers that can meet their needs. However, when requesters are distant from available resources, regular information dissemination techniques can waste communication bandwidth with futile messages. Thus, it may be advantageous to attempt to advertise to select remote regions of the grid, without necessarily also going through all intermediate nodes. This paper proposes dissemination proxies to increase coverage footprints and reduce dissemination overhead. We incorporate selecting and adjusting the amount of proxy nodes into an adaptive dissemination algorithm, and show that dissemination proxies are able to reduce dissemination overhead, and handle available resource distribution scenarios where regular information dissemination approaches may not produce efficient protocols. We also report initial results that indicate that randomly selecting nodes to serve as proxies can perform as well as strategies that select seemingly better-qualified proxies.

The size, complexity, heterogeneity, and dynamism of largescale computational grids make autonomic grid services and solutions necessary. In particular, grid schedulers must map applications onto resources whose state (1) influences the effectiveness of scheduling choices, and (2) changes frequently and considerably. A grid resource state information dissemination service must negotiate the inherent tradeoff between covering a large portion of the grid (so that all schedulers can make informed decisions with the largest number of options), and limiting the protocol’s overhead (i.e. the number of packets sent). This paper argues that probabilistic forwarding protocols must adapt to state changes, because static assignments of forwarding probabilities lead to excessive overhead or lower-than-possible query satisfaction rates in some scenarios. We introduce an approach that compares a node’s local utilization and query generation rates to corresponding rates in the node’s vicinity, and in the grid as a whole. These comparisons, in turn, produce a score that is used to adjust forwarding probabilities. We show that even this simple initial adaptive approach can work better than protocols with static forwarding probability assignments.

Differential Deserialization (DDS) is an optimization technique that exploits similarities between incoming SOAP messages to reduce deserialization time. DDS works by checkpointing the state of the SOAP deserializer at various points while deserializing a message, and using those checkpoints to avoid full deserialization of similar messages. DDS can improve performance in many cases, but its benefit is limited by the potentially significant memory and processing overhead associated with its checkpointing mechanism. Differential checkpointing (DCP) substantially reduces memory use, but still requires significant processing overhead. In this paper, we introduce lightweight checkpointing (LCP), a checkpointing approach that significantly reduces the cost of both DDS and DCP, in terms of both memory use and processing time. LCP statically determines locations in the incoming message where it would be most efficient to create checkpoints. LCP creates checkpoints much faster than both our original DDS checkpointing mechanism and our DCP approach. LCP also has significantly smaller memory requirements. For example, in some of our test cases, LCP requires only 10% of the memory that DCP requires, and only 3% of the memory that our original approach required. In terms of processing time, deserialization with LCP is approximately 50% to 60% faster than without differential deserialization, when approximately half the message is unchanged from the previous message.

Purpose We continue to increase the amount of evaluations to improve the outcomes of our residency programs. Although ongoing faculty evaluations clearly are an important part of faculty development, their value in terms of improving the program needs to be evaluated. The questions asked were as follows: (1) Do faculty evaluations continue to improve the faculty over the course of successive evaluation periods? (2) Are there groups of faculty who would benefit the most from faculty evaluation feedback? (3) Are there any specific objective categories within the evaluation that carry more value and may help to shorten this form? Methods Forty-two faculty members were evaluated by 40 surgical residents with an assessment form developed by surgical residents that assessed faculty members by 10 different criteria. The initial set of data was collected, and attending surgeons were given an intervention in the form of a letter detailing how they had been assessed in each of the 10 categories. The attending surgeons were evaluated again 6 months later and were given an intervention in the form of verbal feedback regarding their evaluations. The attending faculty members were then assessed 1 year after that. One way analyses of variance and Fisher Protected Least Significant Difference (PLSD) were used to analyze the resulting data to determine if there were significant differences in the faculty evaluations. A part–whole correlation was performed that correlated the 10 evaluation criteria against the mean score on each evaluation, and partial η-squared analysis was used to determine which criterion had the largest effect on the overall means. Results The means for the 42 faculty members as a whole continued to improve from the first to the final evaluation period, with 30 faculty members increasing their mean score (18 significantly) and 12 decreasing their mean score (4 significantly). Seven of the 10 evaluation criteria’s means improved sequentially by feedback session. These were (1) Didactic Teaching, (2) Teaching Rounds, (3) Attendance at Didactic Activities, (4) Allows [Resident] Autonomy to Make Independent Decisions, (5) Provides Feedback, (6) Stimulates Critical Thinking with Use of Literature, and (7) Encourages and Maintains an Atmosphere of Professional Mutual Respect for All Members of Health Care Team (Role Model). The faculty group with the lowest evaluations improved significantly more than those of both the middle and the role model group, with the middle and the role model groups improving, but not significantly differently from each other. Of the criteria that improved, only Provides Feedback improved significantly from the first to second and the second to third evaluation periods. The three criteria with the highest correlation coefficients were Role Model (0.76), Provides Feedback (0.75), and Stimulates Critical Thinking (0.74). The results from the partial η-squared test showed that the criterion with the largest effect size was Provides Feedback (0.28). These analyses indicate that the criterion Provides Feedback was both highly correlated with the average score on a faculty member’s evaluation and was more responsible than any other criteria for the overall improvement in the mean evaluation score of the faculty members. Conclusions (1) Ongoing faculty evaluations indeed are a powerful tool to improve the faculty as a whole. (2) The faculty members with the lowest evaluations showed the largest amount of improvement. (3) Providing feedback to the residents seems to be the most valued factor by the residents for faculty evaluations and perhaps could become the basis of the evaluation for the most accomplished faculty.

The SOAP protocol underpins Web services as the standard mechanism for exchanging information in a distributed environment. The XML-based protocol offers advantages including extensibility, interoperability, and robustness. The merger of Web services and grid computing promotes SOAP into a standard protocol for the large-scale scientific applications that computational grids promise to support, further elevating the protocol's importance and requiring high-performance implementations. Various SOAP implementations differ in their implementation language, invocation model and API, and supported performance optimizations. In this paper we compare and contrast the performance of widely used SOAP toolkits and draw conclusions about their current performance characteristics. We also provide insights into various design features that can lead to optimized SOAP implementations. The SOAP implementations included in our study are gSOAP 2.4, AxisC++ CVS May 28, AxisJava 1.2, .NET 1.1.4322 and XS0AP4/XSUL 1.1.

Differential serialization (DDS) is a SOAP optimization technique wherein servers save checkpoints and parser states associated with portions of previously received messages, and use them to avoid full parsing and deserialization of similar new messages. In this paper, we characterize DDS's memory requirements and memory overhead, introduce a new technique for storing only the differences between successive parser states for a message, and demonstrate how this optimization, which we call differential checkpointing, speeds up the DDS optimization and reduces its memory requirements.

Grid information dissemination protocols distribute information about the dynamic state of computational resources throughout interconnected wide area grids. Performance metrics for these protocols include the overhead of information packets, and the accuracy of the information at the time it is used to schedule applications. Our previous work advocated non-uniform protocols to keep dissemination local to the information source, as a method of keeping overhead manageable while achieving adequate freshness and accuracy. This paper considers the problem of providing better control over the dissemination of information and influencing the "coverage footprint" that defines where the information reaches within the grid. The paper describes work that investigates the coverage characteristics of existing protocols and refines and combines them into hybrid protocols that are more controllable. We consider this work to be a necessary step toward adaptive dissemination protocols that would be able to react to the state of grid resources to change dynamically how and where information is disseminated. This in turn increases the effectiveness of grid schedulers under various load levels and distributions

This paper extends the classification approaches described in reference [1] in the following way: (1.) developing and evaluating a new method for evolving organophosphate nerve agent Support Vector Machine (SVM) classifiers using Evolutionary Programming, (2.) conducting research experiments using a larger database of organophosphate nerve agents, and (3.) upgrading the architecture to an object-based grid system for evaluating the classification of EP derived SVMs. Due to the increased threats of chemical and biological weapons of mass destruction (WMD) by international terrorist organizations, a significant effort is underway to develop tools that can be used to detect and effectively combat biochemical warfare. This paper reports the integration of multi-array sensors with Support Vector Machines (SVMs) for the detection of organophosphates nerve agents using a grid computing system called Legion. Grid computing is the use of large collections of heterogeneous, distributed resources (including machines, databases, devices, and users) to support large-scale computations and wide-area data access. Finally, preliminary results using EP derived support vector machines designed to operate on distributed systems have provided accurate classification results. In addition, distributed training time architectures are 50 times faster when compared to standard iterative training time methods.

Beer is typically made from cereal grains. These, however, contain starch and so various strategies are necessary to convert starch to fermentable sugars. Most beer is brewed from specially chosen barley that is wetted, partially germinated, and dried to make malt. This modifies the raw barley to a form suitable for brewing. When malt is ground up and mixed with hot water, malt enzymes rapidly degrade starch to yield a spectrum of fermentable sugars and unfermentable dextrins. The grain extract (wort) is then boiled for an hour with hops, primarily to add bitterness but also to sterilize it. After cooling, a chosen yeast strain is added and fermentation ensues with production of mostly alcohol and carbon dioxide but also a host of flavor compounds each in low concentration. These, in concert with the flavor materials from malt and hops, define beer characteristics, and the brewer's particular choice of yeast, malt, and hops defines a beer brand. The green beer is aged or matured by secondary treatment, filtered and carbonated, and then packaged at high speed and without oxygen access for presentation to the consumer. Beer has some nutritional value and modest daily consumption reduces the risk of coronary heart disease. Keywords: beer; brewing; beverage; barley; malt; hops; fermentation; yeast

The microbiological status of beers rests on three bases: (1) the microbiological quality of the raw materials used, especially, for example, the yeast; (2) the nature of the process and product, including whether or not pasteurization is used; and (3) the sanitary condition of the beer-contact surfaces, that is, the cleanliness of the brewing equipment and the brewery. These three factors define the sanitary and microbiological quality of all beers, whether they be made in large volume or in microbreweries. These three rubrics also define the structure of this chapter. As the general principles of sanitation are dealt with in detail elsewhere in this volume (Chapter 11), only some specific aspects and applications of sanitation that are of particular importance in microbrewing practices and microbrewed products are discussed here. As a result, this chapter is brief.

This study examines the effects of the opioid receptor antagonist, naloxone, and the agonist, morphine, on voluntary wheel-running activity (WR) in rats. Male Sprague-Dawley rats were given 1-h access to a running wheel under non-deprived conditions. Naloxone injections (1.0, 0.5, or 0.25 mg/kg, ip), administered immediately before access to running wheels, dose-dependently suppressed WR. In another experiment, subjects were given 6-h access to running wheels under nondeprived conditions for 5 consecutive days. Morphine injections (2.0 mg/kg, sc) were found to increase WR after an initial suppression. These data demonstrate that naloxone inhibits WR, while morphine both suppresses and enhances WR depending on time and dose. These are in agreement with data on other behaviors that indicate that endogenous opioid systems play a major role in the mediation of motivational behaviors.

During brewing, large volumes of liquid are heated and cooled. Generally, the brewhouse processes, addressed in Chapter 15, are hot processes and the cellar Operations (Chapter 18) are cold ones. These processes work best when heat is transferred efficiently. Brewers, therefore, need some appreciation of the factors involved in heat transfer and refrigeration. The words “heat transfer” describe the transfer of energy from one place to another as a result of temperature difference.