Improve Turnaround Time Research Articles

SPIM workflow manager for HPC.

SummaryHere we introduce a Fiji plugin utilizing the HPC-as-a-Service concept, significantly mitigating the challenges life scientists face when delegating complex data-intensive processing workflows to HPC clusters. We demonstrate on a common Selective Plane Illumination Microscopy image processing task that execution of a Fiji workflow on a remote supercomputer leads to improved turnaround time despite the data transfer overhead. The plugin allows the end users to conveniently transfer image data to remote HPC resources, manage pipeline jobs and visualize processed results directly from the Fiji graphical user interface.Availability and implementationThe code is distributed free and open source under the MIT license. Source code: https://github.com/fiji-hpc/hpc-workflow-manager/, documentation: https://imagej.net/SPIM_Workflow_Manager_For_HPC.Supplementary information Supplementary data are available at Bioinformatics online.

Accelerated bacterial detection in blood culture by enhanced acoustic flow cytometry (AFC) following peptide nucleic acid fluorescence in situ hybridization (PNA-FISH).

Bacteraemia is a risk factor for subsequent clinical deterioration and death. Current reliance on culture-based methods for detection of bacteraemia delays identification and assessment of this risk until after the optimal period for positively impacting treatment decisions has passed. Therefore, a method for rapid detection and identification of bacterial infection in the peripheral bloodstream in acutely ill patients is crucial for improved patient survival through earlier targeted antibiotic treatment. The turnaround time for current clinical laboratory methods ranges from 12 to 48 hours, emphasizing the need for a faster diagnostic test. Here we describe a novel assay for accelerated generic detection of bacteria in blood culture (BC) using peptide nucleic acid fluorescence in situ hybridization enhanced acoustic flow cytometry (PNA-FISH-AFC). For assay development, we used simulated blood cultures (BCs) spiked with one of three bacterial species at a low starting concentration of 10 CFU/mL: Escherichia coli, Klebsiella pneumoniae or Pseudomonas aeruginosa. Under current clinical settings, it takes a minimum of 12 hours incubation to reach positivity on the BacTEC system, corresponding to a bacterial concentration of 107−109 CFU/mL optimal for further analyses. In contrast, our PNA-FISH-AFC assay detected 103–104 CFU/mL bacteria in BC following a much shorter culture incubation of 5 to 10 hours. Using either PCR-based FilmArray assay or MALDI-TOF for bacterial detection, it took 7–10 and 12–24 hours of incubation, respectively, to reach the positive result. These findings indicate a potential time advantage of PNA-FISH-AFC assay for rapid bacterial detection in BC with significantly improved turnaround time over currently used laboratory techniques.

IMMUNE THROMBOCYTOPENIC PURPURA DURING A DENGUE OUTBREAK: A DYNAMIC MASQUERADER

In this age of enhanced diagnostics and improved turnaround time, immune thrombocytopenic purpura (ITP), a disease primarily diagnosed by exclusion, is expected to be straightforward to diagnose. However, during a full-fledged dengue outbreak, the health-care system can be overwhelmed, and as a result, ITP can be underdiagnosed. The clinician should be aware of the various imitations that ITP can present with. Various clinical indicators have to be kept in mind while dealing with such an outbreak to avoid unnecessary health-care expenditure and prolonged hospital stays. In this case series, we present two patients diagnosed to have ITP during the dengue outbreak, each unique in its presentation and course, demonstrating the multiple patterns ITP can present itself.

Novel canine anti-Coccidioides immunoglobulin G enzyme immunoassay aids in diagnosis of coccidioidomycosis in dogs.

The diagnosis of coccidioidomycosis (CM) in dogs is typically based on clinical presentation, serology, and (less frequently) spherule identification. Agar gel immunodiffusion (AGID) is the most commonly employed serological method, but AGID is slow (requiring up to a week for titer). A Coccidioides antigen enzyme immunoassay (EIA) is also available; however, sensitivity is low in CM dogs. An antibody EIA was developed to detect canine immunoglobulin G (IgG) reacting to Coccidioides antigens. Serum was evaluated from dogs with pathology proven CM and/or AGID positive CM, as well as dogs with histoplasmosis, blastomycosis, non-fungal infections, or healthy dogs. A standard curve was used to convert optical density (OD) values into EIA units (EU). Serum and urine samples from CM dogs were also tested in the antigen EIA. Sensitivity and specificity for IgG were 89.2% and 97.2%, respectively, upon evaluation of dogs with proven or probable CM and control dogs. Cross-reactivity was observed in 7.7% and in 6.4% of dogs with histoplasmosis or blastomycosis, respectively. The antigen EIA alone was insensitive (33.8%). Combined IgG and antigen testing increased sensitivity to 93.2%, as three dogs were IgG-negative but had detectable serum or urine antigen. In 22 dogs with proven CM, sensitivity was statistically similar for antibody EIA and AGID (86% and 73%; P = .487). The MiraVista® canine Coccidioides antibody IgG EIA may aid in the diagnosis of CM by improving turnaround time with comparable sensitivity to AGID. Serial or concurrent testing by antibody and antigen EIAs may be beneficial when screening dogs for CM.

Analysing Turnaround Time in Laboratory - A Key Performance Indicator

Background: Turnaround time (TAT) is one of the key indicators of performance of a laboratory. Laboratories define it as the time from the receipt of sample/ specimen to the reporting. A fast TAT helps clinicians in making early diagnosis. Aim: To determine the turnaround time (TAT) of the biochemistry laboratory with evaluation of the contribution of pre-analytical and analytical phase to the total TAT. Results: A total of 399 samples were analysed from three outpatient departments. Average pre-analytical turnaround time contribution was found to be higher as compared to the analytical time. Excess workload and delay in pneumatic shoot were the main causes of delay in pre-analytical phase. Conclusion: Improved turnaround time is the key to clinicians’ and patients’ better satisfaction with the laboratory. It can be attained by minimising the bottlenecks within the process.

Advances in the molecular diagnosis of tuberculosis: From probes to genomes

Tuberculosis, disease caused by Mycobacterium tuberculosis, is currently the leading cause of death by a single infectious agent worldwide. Early, rapid and accurate identification of M. tuberculosis and the determination of drug susceptibility is essential for the treatment and management of this disease. Tuberculosis diagnosis is mainly based on chest radiography, smear microscopy and bacteriological culture. Smear microscopy has variable sensitivity, mainly in patients co-infected with the human immunodeficiency virus (HIV). Conventional culture for M. tuberculosis isolation, identification and drug susceptibility testing requires several weeks owning to the slow growth of M. tuberculosis. The delay in the time to results drives the prolongation of potentially inappropriate antituberculosis therapy contributing to the emergence of drug resistance, reducing treatment options and increasing treatment duration and associated costs, resulting in increased mortality and morbidity. For these reasons, novel diagnostic methods are need for timely identification of M. tuberculosis and determination of the antibiotic susceptibility profile of the infecting strain. Molecular methods offer enhanced sensitivity and specificity, early detection and the capacity to detect mixed infections. These technologies have improved turnaround time, cost effectiveness and are amenable for point-of-care testing. However, although these methods produce results within hours from sample collection, the phenotypic susceptibility testing is still needed for the determination of drug susceptibility and quantify the susceptibility levels of a given strain towards individual antibiotics. This review presents the history, advances and forthcoming promises in the molecular diagnosis of tuberculosis. An overview on the general principles, diagnostic value and the main advantages and disadvantages of the molecular methods used for the detection and identification of M. tuberculosis and its associated disease, is provided. It will be also discussed how the current phenotypic methods should be used in combination with the genotypic methods for rapid antituberculosis susceptibility testing.

1996. Addressing Pulmonary Nocardiosis Risk in Immunocompromised Patients: Development and Validation of a Commercially Available PCR

BackgroundPulmonary nocardiosis is an infection targeting immunocompromised patients characterized by high mortality and requires nonfrontline antibiotics for treatment. Nocardiosis is currently confirmed or excluded by BAL fluid culture followed by further phenotypic identification steps. A culture-independent method with more timely results would accelerate the administration of appropriate treatment. A rapid Nocardia (NOC) PCR assay for BAL has neither been previously validated nor offered for clinical testing to our knowledge.MethodsOligonucleotides for a rapid NOC PCR comprehensive of the causative agents of nocardiosis were aligned to the 16S regions of common NOC species and over 30 others. Specificity was verified against publically available bacterial 16S sequences. Rapid automated nucleic acid extraction (<1 hour for 24 samples) followed by fast PCR (<1 hour) was validated according to relevant compliance standards. Spiked/unspiked human BAL samples were used to assess analytical specificity, limit of detection (LOD), precision and accuracy using NOC and non-NOC strains.ResultsThe NOC PCR detected, among others, the most common NOC species (N. cyriacigeorgica, N. nova, N. farcinica and N. brasiliensis). We estimate more than 95% of causative agents of nocardiosis are detectable by the assay. No cross reactivity was detected from 30 non-NOC bacterial pathogens except for Rhodococcus and Crossiella spp. LOD in BAL fluid was determined to be 206, 41, and 26 copies/mL for N. cyriacigeorgica, N. nova, and N. transvalensis, respectively. Intra- and inter-assay precision studies revealed copies/mL %CV’s of <10% and <8% at a high concentration and <21% and <26% at a low concentration, respectively. Accuracy studies yielded 100% concordance with 33 BAL positives and 20 BAL negatives.ConclusionThe specificity, inclusivity, sensitivity, precision and accuracy of a qualitative PCR have been deployed as an aid in the diagnosis of pulmonary nocardiosis. NOC PCR allows for a culture-independent method that can rapidly detect clinically relevant NOC species with an improved turnaround time, leading to prompt diagnosis and administration of appropriate treatment.Disclosures E. Smith, Viracor Eurofins Clinical Diagnostics: Employee, Salary. K. Bartlett, Viracor Eurofins Clinical Diagnostics: Employee, Salary. J. Grantham, Viracor Eurofins Clinical Diagnostics: Employee, Salary. N. Powell, 1987: Employee, Salary. M. Altrich, Viracor Eurofins Clinical Diagnostics: Employee, Salary. S. Kleiboeker, Viracor Eurofins Clinical Diagnostics: Employee, Salary. M. Wissel, Viracor Eurofins Clinical Diagnostics: Employee, Salary.

Quantification of Methotrexate in Human Serum and Plasma by Liquid Chromatography Tandem Mass Spectrometry.

Mass spectrometry (MS) is a highly specific and sensitive technique that is used for the detection of many different analytes with diverse chemical characteristics. It has been adopted by clinical laboratories for the quantification of small molecules and, by extension, has been widely used for therapeutic drug monitoring. It is an attractive alternative to immunoassay methods, because it is not subject to the same interferences. A limitation of MS (relative to immunoassays) is the turnaround time. However, this can be addressed by workflow parallelization with other assays. Herein we describe a tandem LC-MS/MS method for the detection and quantification of methotrexate in human plasma with a lower limit of quantification of 0.01μM and within-assay and between-assay coefficients of variation of less than 15%. This method lacks interference from high-abundance metabolites and utilizes kindred chromatography to improve turnaround time in the therapeutic drug monitoring laboratory.

Public Cloud: The Future of Record Linkage?

IntroductionBusinesses worldwide are increasingly adopting the storage, compute and analytical services provided by cloud computing. Yet, few operational linkage units are keeping pace with this world of technological change - most use legacy systems approaching their limits with the rapidly increasing size and range of datasets now required for linkage.&#x0D; Objectives and ApproachTo meet the demands of linkage for the near future, it is important that new solutions for linkage consider the services provided by public cloud infrastructure for compute, storage and analytics. We examined Platform as a Service (PaaS) offerings for use in the development of a cost-effective cloud model for scalable, privacy-preserving record linkage (PPRL). PPRL techniques were adapted to maximise the quality of linkage and to automate as much of the process as possible. Finally, a prototype was created to demonstrate the capabilities and potential of the model.&#x0D; ResultsWe present our cloud model for PPRL, a platform for record linkage that provides rapid scaling of resources to meet demand, and the results of how our prototype performed on massive datasets.&#x0D; Conclusion/ImplicationsThe application of record linkage using relatively inexpensive cloud infrastructure represents a significant step towards providing an efficient and scalable record linkage service to researchers and government. Larger datasets can be linked efficiently, including national or cross-jurisdictional datasets, with little investment in private infrastructure, and improved turnaround times for researchers.

Development and application of two multiplex real-time PCR assays for detection and speciation of bacterial pathogens in the koala.

Infectious diseases have contributed to the decline in the health of koala ( Phascolarctos cinereus) populations in the wild in some regions of Australia. Herein we report the development and validation of 2 multiplex real-time PCR (rtPCR) panels for the simultaneous detection of Mycoplasma spp., Ureaplasma spp., Bordetella bronchiseptica, and Chlamydia, including speciation and quantification of Chlamydia, in ocular, reproductive, and nasal swab samples in addition to semen and male urogenital and reproductive tissues, from koalas. Each rtPCR panel was developed for use as a single-tube reaction using pathogen-specific primers and fluorescently labeled probe sets. DNA extracted from reference strains and isolates was used for validation of sequence gene targets for the multiplex rtPCR panels. Each panel was shown to be sensitive and specific in detecting and differentiating the bacterial pathogens. The multiplex rtPCR panels were used to screen clinical samples from free-ranging and hospitalized koalas for multiple pathogens simultaneously. The multiplex rtPCR will improve turnaround time compared to individual-pathogen rtPCR methods used, to date, for confirmation of diagnosis and will provide the wildlife clinician with the ability to make treatment decisions more rapidly.

Data-Driven Methods for Advancing Precision Oncology.

This article discusses the advances, methods, challenges, and future directions of data-driven methods in advancing precision oncology for biomedical research, drug discovery, clinical research, and practice. Precision oncology provides individually tailored cancer treatment by considering an individual's genetic makeup, clinical, environmental, social, and lifestyle information. Challenges include voluminous, heterogeneous, and disparate data generated by different technologies with multiple modalities such as Omics, electronic health records, clinical registries and repositories, medical imaging, demographics, wearables, and sensors. Statistical and machine learning methods have been continuously adapting to the ever-increasing size and complexity of data. Precision Oncology supportive analytics have improved turnaround time in biomarker discovery and time-to-application of new and repurposed drugs. Precision oncology additionally seeks to identify target patient populations based on genomic alterations that are sensitive or resistant to conventional or experimental treatments. Predictive models have been developed for cancer progression and survivorship, drug sensitivity and resistance, and identification of the most suitable combination treatments for individual patient scenarios. In the future, clinical decision support systems need to be revamped to better incorporate knowledge from precision oncology, thus enabling clinical practitioners to provide precision cancer care. Open Omics datasets, machine learning algorithms, and predictive models have enabled the advancement of precision oncology. Clinical decision support systems with integrated electronic health record and Omics data are needed to provide data-driven recommendations to assist clinicians in disease prevention, early identification, and individualized treatment. Additionally, as cancer is a constantly evolving disorder, clinical decision systems will need to be continually updated based on more recent knowledge and datasets.

Interfacing Complex Laboratory Instruments during a Change to Epic Beaker

Background: Implementing a laboratory-developed test sometimes requires incorporating an unconventional device into the laboratory information system (LIS) and customizing an interface to reduce transcription error and improve turnaround time. Such a custom interface is a necessity for complicated high-volume tests such as 25-OH Vitamin D by liquid chromatography-tandem mass spectrometry (LC-MS/MS) when there is no vendor-or LIS-supplied interface available. Here, we describe our work and experience interfacing a API 5000 LC-MS/MS instrument with our newly implemented LIS, Epic Beaker, using a combination of in-house scripting software and a middleware vendor, Data Innovations. Materials and Methods: For input interfacing, custom scripting software was developed to transcribe batched order lists generated by Epic into files usable by the instrument software, Analyst®. For output interfacing, results from the LC-MS/MS system were fed to a unidirectional instrument driver made by Data Innovations and selected data were transferred to the LIS. Results: Creation and validation of a new driver by Data Innovations took approximately 6 months. The interface was adopted for 25-OH Vitamin D and testosterone testing during periods of increasing test volume (4.5-fold over 8 years and 1.25-fold over 5 years). The amount of time spent reporting 25-OH Vitamin D results decreased 82% per order resulting in a savings of 1370 technician work hours and the amount of time spent reporting testosterone results decreased 75% per order resulting in a savings of 400 technician work hours. Conclusions: A mixed model using custom scripting and curated commercial middleware serve as a durable interface solution for laboratory instrumentation such as an LC-MS/MS and are flexible to future changes in instrument software, networking protocols, and the scope of LISs and work area managers.

Upfront dilution of ferritin samples to reduce hook effect, improve turnaround time and reduce costs.

IntroductionSandwich immunoassays offer advantages in the clinical laboratory but can yield erroneously low results due to hook (prozone) effect, especially with analytes whose concentrations span several orders of magnitude such as ferritin. This study investigated a new approach to reduce the likelihood of hook effect in ferritin immunoassays by performing upfront, five-fold dilutions of all samples for ferritin analysis. The impact of this change on turnaround time and costs were also investigated.Materials and methodsFerritin concentrations were analysed in routine clinical practice with and without upfront dilutions on Siemens Centaur® XP (Siemens Healthineers, Erlang, Germany) immunoanalysers. In addition, one month of baseline data (1026 results) were collected prior to implementing upfront dilutions and one month of data (1033 results) were collected after implementation.ResultsWithout upfront dilutions, hook effect was observed in samples with ferritin concentrations as low as 86,028 µg/L. With upfront dilutions, samples with ferritin concentrations as high as 126,050 µg/L yielded values greater than the measurement interval and would have been diluted until an accurate value was obtained. The implementation of upfront dilution of ferritin samples led to a decrease in turnaround time from a median of 2 hours and 3 minutes to 1 hour and 18 minutes (P = 0.002).ConclusionsImplementation of upfront dilutions of all ferritin samples reduced the possibility of hook effect, improved turnaround time and saved the cost of performing additional dilutions.

Influence of nursing management model based on information-motivation-behavioral skills on treatment compliance and quality of life of elderly patients with chronic obstructive pulmonary disease

Objective To observe the influence of nursing management model based on information-motivation-behavioral skills on treatment compliance and quality of life of elderly patients with chronic obstructive pulmonary disease (COPD). Methods According to stochastic sequential synthesis equilibrium method, 104 cases of elderly patients with COPD were divided into study group with 52 cases and control group with 52 cases.The control group were given the routine nursing management, while the study group were given nursing management model based on information-motivation-behavioral skills.Time for improved or disappeared symptoms and results of 6 MWT was observed.The treatment compliance and quality of life of patients of the two groups were compared. Results Improved breathing time, improved turnaround time and disappeared time of breathing difficulties of the study group were significantly less than that of the control group (P<0.05) and 6 MWT of the former was much higher than that of the latter (P<0.05). Compliance scores of prescribed medication, behavior habits and rehabilitation training, etc.of the study group were significantly higher than that of the control group (P<0.05). Scores of quality of life in all dimensions of the two groups were significantly higher than that before intervention (P<0.05), and the scores of the study group were significantly higher than that of the control group (P<0.05). Conclusions Nursing management model based on information-motivation-behavioral skills applied to elderly patients with COPD not only can speed up the improvement of symptoms, but also improve treatment compliance and quality of life. Key words: Information-motivation-behavioral skills; Nursing management; Chronic obstructive pulmonary disease; Compliance; Quality of life

Reducing diagnostic turnaround times of exome sequencing for families requiring timely diagnoses

Background and objectiveWhole-exome sequencing (WES) has now entered medical practice with powerful applications in the diagnosis of rare Mendelian disorders. Although the usefulness and cost-effectiveness of WES have been widely demonstrated, it is essential to reduce the diagnostic turnaround time to make WES a first-line procedure. Since 2011, the automation of laboratory procedures and advances in sequencing chemistry have made it possible to carry out diagnostic whole genome sequencing from the blood sample to molecular diagnosis of suspected genetic disorders within 50 h. Taking advantage of these advances, the main objective of the study was to improve turnaround times for sequencing results. MethodsWES was proposed to 29 patients with severe undiagnosed disorders with developmental abnormalities and faced with medical situations requiring rapid diagnosis. Each family gave consent. The extracted DNA was sequenced on a NextSeq500 (Illumina) instrument. Data were analyzed following standard procedures. Variants were interpreted using in-house software. Each rare variant affecting protein sequences with clinical relevance was tested for familial segregation. ResultsThe diagnostic rate was 45% (13/29), with a mean turnaround time of 40 days from reception of the specimen to delivery of results to the referring physician. Besides permitting genetic counseling, the rapid diagnosis for positive families led to two pre-natal diagnoses and two inclusions in clinical trials. ConclusionsThis pilot study demonstrated the feasibility of rapid diagnostic WES in our primary genetics center. It reduced the diagnostic odyssey and helped provide support to families.

Evaluation of a Novel Reporter Virus Neutralization Test for Serological Diagnosis of Zika and Dengue Virus Infection.

ABSTRACTCurrently, the laboratory diagnosis of Zika virus (ZIKV) infection is primarily through the detection of ZIKV RNA or antibodies against ZIKV proteins. The detection of viral RNA is highly sensitive and specific, but periods of viremia and viruria are brief, limiting the utility of ZIKV RNA assays. Instead, most ZIKV infections are diagnosed serologically, using an IgM antibody capture enzyme-linked immunosorbent assay (MAC-ELISA) for screening, followed by a confirmatory plaque reduction neutralization test (PRNT). Typical turnaround times vary, due to assay incubation periods and a lack of clinical laboratories performing these tests. Recently, a novel luciferase-ZIKV- and -dengue virus (DENV)-based serological assay, which considerably improves the turnaround times and throughput for ZIKV diagnosis, was described. Using the traditional PRNT as a reference method, we evaluated the performance characteristics of the reporter virus neutralization test (RVNT) with 258 clinical serum specimens. The ZIKV RVNT produced primary ZIKV screening and secondary confirmation results in 4 days, with 100% reproducibility. As a screening assay, the ZIKV RVNT displayed excellent diagnostic accuracy, sensitivity, and specificity of 98.2%, 100%, and 98.1%, respectively. As a confirmatory assay, the ZIKV RVNT titers displayed 93.1% agreement with the traditional ZIKV PRNT titers. Overall, the RVNT accurately and reliably detects neutralizing antibodies in patient serum specimens, with improved turnaround times, and can be used for the serological detection of ZIKV infections. Due to the homogeneous 96-well format, the RVNT has also significantly improved the assay throughput to allow testing of a large number of specimens in a single run.

Nonanalytic Laboratory Automation: A Quarter Century of Progress.

Clinical laboratory automation has blossomed since the 1989 AACC meeting, at which Dr. Masahide Sasaki first showed a western audience what his laboratory had implemented. Many diagnostics and other vendors are now offering a variety of automated options for laboratories of all sizes. Replacing manual processing and handling procedures with automation was embraced by the laboratory community because of the obvious benefits of labor savings and improvement in turnaround time and quality. Automation was also embraced by the diagnostics vendors who saw automation as a means of incorporating the analyzers purchased by their customers into larger systems in which the benefits of automation were integrated to the analyzers.This report reviews the options that are available to laboratory customers. These options include so called task-targeted automation-modules that range from single function devices that automate single tasks (e.g., decapping or aliquoting) to multifunction workstations that incorporate several of the functions of a laboratory sample processing department. The options also include total laboratory automation systems that use conveyors to link sample processing functions to analyzers and often include postanalytical features such as refrigerated storage and sample retrieval.Most importantly, this report reviews a recommended process for evaluating the need for new automation and for identifying the specific requirements of a laboratory and developing solutions that can meet those requirements. The report also discusses some of the practical considerations facing a laboratory in a new implementation and reviews the concept of machine vision to replace human inspections.

Personalized and precision medicine: integrating genomics into treatment decisions in gastrointestinal malignancies.

The advent of next generation sequencing (NGS) technologies has advanced our understanding of the intrinsic biology of different gastrointestinal (GI) tumor types. The use of novel, more efficient sequencing platforms has improved turnaround times of sequencing results. This is providing real time opportunities to put precision medicine to the test. A number of early phase clinical trials are testing targeted therapies in unique molecularly characterized subsets of patients (baskets). While basket studies are gaining momentum, treatment failures serve to remind us that shifting from a histology-driven to a histology-agnostic approach is unlikely to be a failure-free strategy for a number of tumor types as recently learnt from vemurafenib failure in BRAF mutated metastatic colorectal cancer (mCRC). GI malignancies are clinically and molecularly heterogeneous. Unfortunately, development of biomarkers of response to therapy as well as targeted therapies for GI adenocarcinomas has fallen behind compared to other malignancies. Trastuzumab is the only FDA approved targeted therapy for GI adenocarcinomas for which a biomarker of response (HER2 amplifications) is available. In addition, RAS mutations are known to predict lack of response to epidermal growth factor receptor (EGFR) inhibitors in advanced colorectal cancer (CRC) patients. However, NGS has recently revealed that a number of actionable genetic aberrations are present at low prevalence across different GI malignancies. Prospective randomized clinical trials will determine whether matching actionable aberration with targeted therapy will contribute to improve survival in patients with GI malignancies. Here, we review current evidence for targeted therapies in GI malignancies, as well as application and pitfalls of NGS including tissue testing and liquid biopsies.

A process-driven platform to manage datasets for research

ABSTRACT&#x0D; Objectives&#x0D; &#x0D; Accumulate, manage and control shared access to research data; &#x0D; Transform and maintain transformation state information about research data; &#x0D; Analyse and investigate data in related sets using open and bespoke tools; &#x0D; Publish extracted data to a secure safe haven environment.&#x0D; &#x0D; ApproachThe Research Data Management Platform (RDMP) is a set of data structures and processes, sharing a core Catalogue, to manage electronic health records, genomic data and imaging data throughout their lifecycle from identification and acquisition to safe disposal or archival and retention in secured Safe Havens (SH).&#x0D; The architecture components of the RDMP consist of the Catalogue and five internal processes: Data Load, Catalogue Management, Data Quality, Data Summary, and Data Extraction. These are designed to enforce rigorous information governance standards relevant to the processing and anonymisation of personal identifiable data. The Catalogue serves as the single ‘source of truth’ about the datasets which all RDMP processes consult. This facilitates repeatable, reliable and auditable operations on the data.&#x0D; The novelty of the RDMP is that it dynamically and seamlessly captures and preserves data transformation processes along with the primary research data to promote reuse and curation of continuously accruing research data repositories in a secure SH environment. Thus, the RDMP brings transparency and reproducibility that benefits research programmes in a way that archival of static data objects does not.&#x0D; ResultsThe RDMP has been in production use since July 1st 2014. There are 107 datasets configured in the Catalogue, with up to 67 dataset extractions for each of 48 research projects. It has provided data for 32 high-impact journal papers published in the last year.&#x0D; Improvements in turnaround time:&#x0D; &#x0D; Research project data provision reduced from six months to two weeks;&#x0D; Data loading reduced from two days to a few hours; &#x0D; Research query response reduced from days to within a day, due to improved and standardised metadata catalogue&#x0D; &#x0D; ConclusionThe RDMP is a key component in automating the regular release of datasets and rationalising dataset changes over time to ensure reliable delivery of extracts to research projects. The tools and processes comprising the RDMP not only fulfil the RDM requirements of researchers, but also support seamless collaboration of data cleaning, data transformation, data summarisation and data quality assessment activities by different research groups.

Evaluation of the SD Bioline TB Ag MPT64 test for identification of Mycobacterium tuberculosis complex from liquid cultures in Southwestern Uganda.

BackgroundTo confirm presence of Mycobacterium tuberculosis complex, some tuberculosis culture laboratories still rely on para-nitrobenzoic acid (PNB), a traditional technique that requires sub-culturing of clinical isolates and two to three weeks to give results. Rapid identification tests have improved turnaround times for mycobacterial culture results. Considering the challenges of the PNB method, we assessed the performance of the SD Bioline TB Ag MPT64 assay by using PNB as gold standard to detect M. tuberculosis complex from acid-fast bacilli (AFB) positive cultures.ObjectivesThe aim of this study was to determine the sensitivity, specificity and turnaround time of the SD MPT64 assay for identification of M. tuberculosis complex, in a setting with high prevalence of tuberculosis and HIV.MethodsA convenience sample of 690 patients, with tuberculosis symptoms, was enrolled at Epicentre Mbarara Research Centre between April 2010 and June 2011. The samples were decontaminated using NALC-NaOH and re-suspended sediments inoculated in Mycobacterium Growth Indicator Tubes (MGIT) media, then incubated at 37 °C for a maximum of eight weeks. A random sample of 50 known negative cultures and 50 non-tuberculous mycobacteria isolates were tested for specificity, while sensitivity was based on AFB positivity. The time required from positive culture to reporting of results was also assessed with PNB used as the gold standard.ResultsOf the 138 cultures that were AFB-positive, the sensitivity of the SD MPT64 assay was 100.0% [95% CI: 97.3 – 100] and specificity was 100.0% (95% CI, 96.4 – 100). The median time from a specimen receipt to confirmation of strain was 10 days [IQR: 8–12] with SD MPT64 and 24 days [IQR: 22–26] with PNB.ConclusionThe SD MPT64 assay is comparable to PNB for identification of M. tuberculosis complex and reduces the time to detection.