Migrating medical communications software to a multi-tenant cloud environment

The rise of cloud computing has paved the way for many new applications. Many of these new cloud applications are also multi-tenant, ensuring multiple end users can make use of the same application instance. While these technologies make it possible to create many new applications, many legacy applications can also benefit from the added flexibility and cost-savings of cloud computing and multi-tenancy. In this paper, we describe the steps required to migrate a. NET-based medical communications application to the Windows Azure public cloud environment, and the steps required to add multi-tenancy to the application. We then discuss the advantages and disadvantages of our migration approach. We found that the migration to the cloud itself requires only a limited amount of changes to the application, but that this also limited the benefits, as individual instances would only be partially used. Adding multi-tenancy requires more changes, but when this is done, it has the potential to greatly reduce the cost of running the application

Genome sequence and characterization of Streptomyces phage Pablito, representing a new species within the genus Janusvirus

Streptomycetes are ubiquitous soil bacteria. Here we report the complete and annotated genome sequence and characterization of Streptomyces phage Pablito, isolated from a soil sample in Haarlem, the Netherlands using Streptomyces lividans as host. This phage was able to infect a diverse range of Streptomyces strains, but none belonging to the sister genus Kitasatospora. Phage Pablito has double-stranded DNA with a genome length of 49,581 base pairs encoding 76 putative proteins, of which 26 could be predicted. The presence of a serine integrase protein indicated the lysogenic nature of phage Pablito. The phage remained stable over a wide range of temperatures (25--45 \textdegreeC) and at pH\thinspace\thinspace7.0, but lost infectivity at temperatures above 55 \textdegreeC or when the pH dropped below 6.0. This newly isolated phage is closely related to Streptomyces phage Janus and Hank144 and considered a new species classified in the genus Janusvirus, within the subfamily Arquattrovirinae.This work was funded by a VICI grant from the Dutch Research Council (NWO) to DC (Grant Number VI.C.192.002) and an NWO XS grant to AB (Grant Number OCENW.XS.041). Microscope access was supported by the Netherlands Center for Electron Nanoscopy and partially funded by the Netherlands Electron Microscopy Infrastructure Grant 84.034.014.info:eu-repo/semantics/publishedVersio

Ambient-aware continuous care through semantic context dissemination

Background: The ultimate ambient-intelligent care room contains numerous sensors and devices to monitor the patient, sense and adjust the environment and support the staff. This sensor-based approach results in a large amount of data, which can be processed by current and future applications, e. g., task management and alerting systems. Today, nurses are responsible for coordinating all these applications and supplied information, which reduces the added value and slows down the adoption rate. The aim of the presented research is the design of a pervasive and scalable framework that is able to optimize continuous care processes by intelligently reasoning on the large amount of heterogeneous care data. Methods: The developed Ontology-based Care Platform (OCarePlatform) consists of modular components that perform a specific reasoning task. Consequently, they can easily be replicated and distributed. Complex reasoning is achieved by combining the results of different components. To ensure that the components only receive information, which is of interest to them at that time, they are able to dynamically generate and register filter rules with a Semantic Communication Bus (SCB). This SCB semantically filters all the heterogeneous care data according to the registered rules by using a continuous care ontology. The SCB can be distributed and a cache can be employed to ensure scalability. Results: A prototype implementation is presented consisting of a new-generation nurse call system supported by a localization and a home automation component. The amount of data that is filtered and the performance of the SCB are evaluated by testing the prototype in a living lab. The delay introduced by processing the filter rules is negligible when 10 or fewer rules are registered. Conclusions: The OCarePlatform allows disseminating relevant care data for the different applications and additionally supports composing complex applications from a set of smaller independent components. This way, the platform significantly reduces the amount of information that needs to be processed by the nurses. The delay resulting from processing the filter rules is linear in the amount of rules. Distributed deployment of the SCB and using a cache allows further improvement of these performance results

Hevin is down-regulated in many cancers and is a negative regulator of cell growth and proliferation

We have cloned a human Hevin cDNA from omental adipose tissue of different patients by reverse transcription polymerase chain reaction and shown a sequence variation due to a possible polymorphism at amino acid position 161 (E/G). Hevin protein expressed in vitro showed molecular weights of approximately 75 kDa and 150 kDa, suggesting that Hevin may form a homodimer in vitro. Using Northern blots and a human expressed sequence tAg database analysis, Hevin was shown to be widely expressed in human normal or non-neoplastic diseased tissues with various levels. In contrast to this, its expression was strongly down-regulated in most neoplastic cells or tissues tested. However, neither the mechanism nor the physiological meaning of this down-regulation is known. As an initial step towards investigating the functional role of Hevin in cell growth and differentiation, we transiently or stably expressed this gene in cancer cells (HeLa 3S) that are devoid of endogenous Hevin and measured DNA synthesis (cell proliferation) by 5-bromo-2′-deoxyuridine incorporation. Hevin was shown to be a negative regulator of cell proliferation. Furthermore, we have shown that Hevin can inhibit progression of cells from G1 to S phase or prolong G1 phase. This is the first report which describes the function of Hevin in cell growth and proliferation. Through database analysis, Hevin was found to be located on chromosome 4 which contains loss of heterozygosity of many tumour suppressor genes. Taken together, these results suggest that Hevin may be a candidate for a tumour suppressor gene and a potential target for cancer diagnosis/therapy. © 2000 Cancer Research Campaig

An ontology-based nurse call management system (oNCS) with probabilistic priority assessment

<p>Abstract</p> <p>Background</p> <p>The current, place-oriented nurse call systems are very static. A patient can only make calls with a button which is fixed to a wall of a room. Moreover, the system does not take into account various factors specific to a situation. In the future, there will be an evolution to a mobile button for each patient so that they can walk around freely and still make calls. The system would become person-oriented and the available context information should be taken into account to assign the correct nurse to a call.</p> <p>The aim of this research is (1) the design of a software platform that supports the transition to mobile and wireless nurse call buttons in hospitals and residential care and (2) the design of a sophisticated nurse call algorithm. This algorithm dynamically adapts to the situation at hand by taking the profile information of staff members and patients into account. Additionally, the priority of a call probabilistically depends on the risk factors, assigned to a patient.</p> <p>Methods</p> <p>The <it>ontology-based Nurse Call System (oNCS) </it>was developed as an extension of a <it>Context-Aware Service Platform</it>. An ontology is used to manage the profile information. Rules implement the novel nurse call algorithm that takes all this information into account. Probabilistic reasoning algorithms are designed to determine the priority of a call based on the risk factors of the patient.</p> <p>Results</p> <p>The <it>oNCS </it>system is evaluated through a prototype implementation and simulations, based on a detailed dataset obtained from Ghent University Hospital. The arrival times of nurses at the location of a call, the workload distribution of calls amongst nurses and the assignment of priorities to calls are compared for the <it>oNCS </it><it>system </it>and the current, place-oriented nurse call system. Additionally, the performance of the system is discussed.</p> <p>Conclusions</p> <p>The execution time of the nurse call algorithm is on average 50.333 ms. Moreover, the <it>oNCS system </it>significantly improves the assignment of nurses to calls. Calls generally have a nurse present faster and the workload-distribution amongst the nurses improves.</p

Development and evaluation of uncertainty quantifying machine learning models to predict piperacillin plasma concentrations in critically ill patients

Background: Beta-lactam antimicrobial concentrations are frequently suboptimal in critically ill patients. Population pharmacokinetic (PopPK) modeling is the golden standard to predict drug concentrations. However, currently available PopPK models often lack predictive accuracy, making them less suited to guide dosing regimen adaptations. Furthermore, many currently developed models for clinical applications often lack uncertainty quantification. We, therefore, aimed to develop machine learning (ML) models for the prediction of piperacillin plasma concentrations while also providing uncertainty quantification with the aim of clinical practice. Methods: Blood samples for piperacillin analysis were prospectively collected from critically ill patients receiving continuous infusion of piperacillin/tazobactam. Interpretable ML models for the prediction of piperacillin concentrations were designed using CatBoost and Gaussian processes. Distribution-based Uncertainty Quantification was added to the CatBoost model using a proposed Quantile Ensemble method, useable for any model optimizing a quantile function. These models are subsequently evaluated using the distribution coverage error, a proposed interpretable uncertainty quantification calibration metric. Development and internal evaluation of the ML models were performed on the Ghent University Hospital database (752 piperacillin concentrations from 282 patients). Ensuing, ML models were compared with a published PopPK model on a database from the University Medical Centre of Groningen where a different dosing regimen is used (46 piperacillin concentrations from 15 patients.). Results: The best performing model was the Catboost model with an RMSE and R-2 of 31.94-0.64 and 33.53-0.60 for internal evaluation with and without previous concentration. Furthermore, the results prove the added value of the proposed Quantile Ensemble model in providing clinically useful individualized uncertainty predictions and show the limits of homoscedastic methods like Gaussian Processes in clinical applications. Conclusions: Our results show that ML models can consistently estimate piperacillin concentrations with acceptable and high predictive accuracy when identical dosing regimens as in the training data are used while providing highly relevant uncertainty predictions. However, generalization capabilities to other dosing schemes are limited. Notwithstanding, incorporating ML models in therapeutic drug monitoring programs seems definitely promising and the current work provides a basis for validating the model in clinical practice

A systematic review of natural health product treatment for vitiligo

<p>Abstract</p> <p>Background</p> <p>Vitiligo is a hypopigmentation disorder affecting 1 to 4% of the world population. Fifty percent of cases appear before the age of 20 years old, and the disfigurement results in psychiatric morbidity in 16 to 35% of those affected.</p> <p>Methods</p> <p>Our objective was to complete a comprehensive, systematic review of the published scientific literature to identify natural health products (NHP) such as vitamins, herbs and other supplements that may have efficacy in the treatment of vitiligo. We searched eight databases including MEDLINE and EMBASE for vitiligo, leucoderma, and various NHP terms. Prospective controlled clinical human trials were identified and assessed for quality.</p> <p>Results</p> <p>Fifteen clinical trials were identified, and organized into four categories based on the NHP used for treatment. 1) L-phenylalanine monotherapy was assessed in one trial, and as an adjuvant to phototherapy in three trials. All reported beneficial effects. 2) Three clinical trials utilized different traditional Chinese medicine products. Although each traditional Chinese medicine trial reported benefit in the active groups, the quality of the trials was poor. 3) Six trials investigated the use of plants in the treatment of vitiligo, four using plants as photosensitizing agents. The studies provide weak evidence that photosensitizing plants can be effective in conjunction with phototherapy, and moderate evidence that <it>Ginkgo biloba </it>monotherapy can be useful for vitiligo. 4) Two clinical trials investigated the use of vitamins in the therapy of vitiligo. One tested oral cobalamin with folic acid, and found no significant improvement over control. Another trial combined vitamin E with phototherapy and reported significantly better repigmentation over phototherapy only. It was not possible to pool the data from any studies for meta-analytic purposes due to the wide difference in outcome measures and poor quality ofreporting.</p> <p>Conclusion</p> <p>Reports investigating the efficacy of NHPs for vitiligo exist, but are of poor methodological quality and contain significant reporting flaws. L-phenylalanine used with phototherapy, and oral <it>Ginkgo biloba </it>as monotherapy show promise and warrant further investigation.</p

Ginkgo biloba for the treatment of vitilgo vulgaris: an open label pilot clinical trial

<p>Abstract</p> <p>Background</p> <p>Vitiligo is a common hypopigmentation disorder with significant psychological impact if occurring before adulthood. A pilot clinical trial to determine the feasibility of an RCT was conducted and is reported here.</p> <p>Methods</p> <p>12 participants 12 to 35 years old were recruited to a prospective open-label pilot trial and treated with 60 mg of standardized <it>G. biloba </it>two times per day for 12 weeks. The criteria for feasibility included successful recruitment, 75% or greater retention, effectiveness and lack of serious adverse reactions. Effectiveness was assessed using the Vitiligo Area Scoring Index (VASI) and the Vitiligo European Task Force (VETF), which are validated outcome measures evaluating the area and intensity of depigmentation of vitiligo lesions. Other outcomes included photographs and adverse reactions. Safety was assessed by serum coagulation factors (platelets, PTT, INR) at baseline and week 12.</p> <p>Results</p> <p>After 2 months of recruitment, the eligible upper age limit was raised from 18 to 35 years of age in order to facilitate recruitment of the required sample size. Eleven participants completed the trial with 85% or greater adherence to the protocol. The total VASI score improved by 0.5 (P = 0.021) from 5.0 to 4.5, range of scale 0 (no depigmentation) to 100 (completely depigmented). The progression of vitiligo stopped in all participants; the total VASI indicated an average repigmentation of vitiligo lesions of 15%. VETF total vitiligo lesion area decreased 0.4% (P = 0.102) from 5.9 to 5.6 from baseline to week 12. VETF staging score improved by 0.7 (P = 0.101) from 6.6 to 5.8, and the VETF spreading score improved by 3.9 (P < 0.001)) from 2.7 to -1.2. There were no statistically significant changes in platelet count, PTT, or INR.</p> <p>Conclusions</p> <p>The criteria for feasibility were met after increasing the maximum age limit of the successful recruitment criterion; participant retention, safety and effectiveness criteria were also met. Ingestion of 60 mg of <it>Ginkgo biloba </it>BID was associated with a significant improvement in total VASI vitiligo measures and VETF spread, and a trend towards improvement on VETF measures of vitiligo lesion area and staging. Larger, randomized double-blind clinical studies are warranted and appear feasible.</p> <p>Trial Registration</p> <p>Clinical trials.gov registration number <a href="http://www.clinicaltrials.gov/ct2/show/NCT00907062">NCT00907062</a></p