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MRIGlobal is an American independent, not-for-profit , contract research organization based in Kansas City, Missouri , with regional offices in Virginia and Maryland. In addition to its own research laboratories, MRIGlobal operates research facilities for the Department of Energy and the Department of Defense .

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65-472: MRIGlobal conducts programs in the areas of molecular diagnostics , antimicrobial resistance, therapeutics , engineering , mobile laboratories , CBRNE technology development and countermeasures, chemical testing facilities, real-time biosurveillance, national security and defense , energy and the environment , and agriculture . The purpose of MRIGlobal is to provide solutions through scientific research, technology development, and technical services for

130-431: A company's prospects. In economics, as in finance, risk is often defined as quantifiable uncertainty about gains and losses. Environmental risk arises from environmental hazards or environmental issues . In the environmental context, risk is defined as "The chance of harmful effects to human health or to ecological systems". Environmental risk assessment aims to assess the effects of stressors, often chemicals, on

195-405: A highly quantified way. The technique is usually referred to as probabilistic risk assessment (PRA). See WASH-1400 for an example of this approach. The incidence rate can also be reduced due to the provision of better occupational health and safety programmes. Security is freedom from, or resilience against, potential harm caused by others. A security risk is "any event that could result in

260-400: A large organization or simply crossing the road. Intuitive risk management is addressed under the psychology of risk below. Risk management refers to a systematic approach to managing risks, and sometimes to the profession that does this. A general definition is that risk management consists of "coordinated activities to direct and control an organization with regard to risk". ISO 31000 ,

325-526: A lot of PCR and hybridization assays have been approved by FDA as in vitro diagnostics. NGS assays, however, are still at an early stage in clinical diagnostics. To do the molecular diagnostic test for cancer, one of the significant issue is the DNA sequence variation detection. Tumor biopsy samples used for diagnostics always contain as little as 5% of the target variant as compared to wildtype sequence. Also, for noninvasive applications from peripheral blood or urine,

390-405: A million of different probes can be synthesized on an array with Affymetrix's Genechip technology with a detection limit of one to ten copies of mRNA per well. Optimized microarrays are typically considered to produce repeatable relative quantitation of different targets. Currently, FDA have already approved a number of diagnostics assays utilizing microarrays: Agendia's MammaPrint assays can inform

455-536: A patient. Preservation of the sample before analysis is critical. Manual handling should be minimised. The fragile RNA molecule poses certain challenges. As part of the cellular process of expressing genes as proteins, it offers a measure of gene expression but it is vulnerable to hydrolysis and breakdown by ever-present RNAse enzymes . Samples can be snap-frozen in liquid nitrogen or incubated in preservation agents. Because molecular diagnostics methods can detect sensitive markers, these tests are less intrusive than

520-431: A pool of risks including market risk, credit risk, operational risk, interest rate risk, mortality risk, longevity risks, etc. The term "risk" has a long history in insurance and has acquired several specialised definitions, including "the subject-matter of an insurance contract", "an insured peril" as well as the more common "possibility of an event occurring which causes injury or loss". Occupational health and safety

585-415: A sample of DNA instead, and because of cell-free DNA in plasma, could be less invasive, but as of 2013 it is still an adjunct to the conventional tests. Some of a patient's single nucleotide polymorphisms —slight differences in their DNA—can help predict how quickly they will metabolise particular drugs; this is called pharmacogenomics . For example, the enzyme CYP2C19 metabolises several drugs, such as

650-622: A simple summary, defining risk as "the possibility of something bad happening". The International Organization for Standardization (ISO) 31073 provides basic vocabulary to develop common understanding on risk management concepts and terms across different applications. ISO 31073 defines risk as: effect of uncertainty on objectives Note 1: An effect is a deviation from the expected. It can be positive, negative or both, and can address, create or result in opportunities and threats . Note 2: Objectives can have different aspects and categories, and can be applied at different levels. Note 3: Risk

715-405: A traditional biopsy . For example, because cell-free nucleic acids exist in human plasma , a simple blood sample can be enough to sample genetic information from tumours, transplants or an unborn fetus. Many, but not all, molecular diagnostics methods based on nucleic acids detection use polymerase chain reaction (PCR) to vastly increase the number of nucleic acid molecules, thereby amplifying

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780-521: A variety of hazards that may result in accidents causing harm to people, property and the environment. In the safety field, risk is typically defined as the "likelihood and severity of hazardous events". Safety risks are controlled using techniques of risk management. A high reliability organisation (HRO) involves complex operations in environments where catastrophic accidents could occur. Examples include aircraft carriers, air traffic control, aerospace and nuclear power stations. Some HROs manage risk in

845-528: Is a collection of techniques used to analyze biological markers in the genome and proteome , and how their cells express their genes as proteins , applying molecular biology to medical testing . In medicine the technique is used to diagnose and monitor disease, detect risk, and decide which therapies will work best for individual patients, and in agricultural biosecurity similarly to monitor crop- and livestock disease , estimate risk , and decide what quarantine measures must be taken. By analysing

910-510: Is a disease with excessive molecular causes and constant evolution. There's also heterogeneity of disease even in an individual. Molecular studies of cancer have proved the significance of driver mutations in the growth and metastasis of tumors. Many technologies for detection of sequence variations have been developed for cancer research. These technologies generally can be grouped into three approaches: polymerase chain reaction (PCR), hybridization, and next-generation sequencing (NGS). Currently,

975-494: Is a questionnaire screening tool, used to provide individuals with an evaluation of their health risks and quality of life. Health, safety, and environment (HSE) are separate practice areas; however, they are often linked. The reason is typically to do with organizational management structures; however, there are strong links among these disciplines. One of the strongest links is that a single risk event may have impacts in all three areas, albeit over differing timescales. For example,

1040-416: Is an individual or collaborative undertaking planned to achieve a specific aim. Project risk is defined as, "an uncertain event or condition that, if it occurs, has a positive or negative effect on a project's objectives". Project risk management aims to increase the likelihood and impact of positive events and decrease the likelihood and impact of negative events in the project. Safety is concerned with

1105-471: Is concerned with occupational hazards experienced in the workplace. The Occupational Health and Safety Assessment Series (OHSAS) standard OHSAS 18001 in 1999 defined risk as the "combination of the likelihood and consequence(s) of a specified hazardous event occurring". In 2018 this was replaced by ISO 45001 "Occupational health and safety management systems", which use the ISO Guide 73 definition. A project

1170-503: Is ethically complex: patients may not want the stress of knowing their risk. In countries without universal healthcare, a known risk may raise insurance premiums. Cancer is a change in the cellular processes that cause a tumour to grow out of control. Cancerous cells sometimes have mutations in oncogenes , such as KRAS and CTNNB1 (β-catenin). Analysing the molecular signature of cancerous cells—the DNA and its levels of expression via messenger RNA —enables physicians to characterise

1235-432: Is narrowly focused on computer security, information risks extend to other forms of information (paper, microfilm). Insurance is a risk treatment option which involves risk sharing. It can be considered as a form of contingent capital and is akin to purchasing an option in which the buyer pays a small premium to be protected from a potential large loss. Insurance risk is often taken by insurance companies, who then bear

1300-458: Is the possibility of something bad happening. Risk involves uncertainty about the effects/implications of an activity with respect to something that humans value (such as health, well-being, wealth, property or the environment), often focusing on negative, undesirable consequences. Many different definitions have been proposed. One international standard definition of risk is the "effect of uncertainty on objectives". The understanding of risk,

1365-472: Is the use of computers to store, retrieve, transmit, and manipulate data. IT risk (or cyber risk) arises from the potential that a threat may exploit a vulnerability to breach security and cause harm. IT risk management applies risk management methods to IT to manage IT risks. Computer security is the protection of IT systems by managing IT risks. Information security is the practice of protecting information by mitigating information risks. While IT risk

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1430-436: Is usually expressed in terms of risk sources, potential events, their consequences and their likelihood. This definition was developed by an international committee representing over 30 countries and is based on the input of several thousand subject-matter experts. It was first adopted in 2002 for use in standards. Its complexity reflects the difficulty of satisfying fields that use the term risk, in different ways. Some restrict

1495-503: The Nelson Art Gallery , and adjacent to University of Missouri - Kansas City and the headquarters of Russell Stovers candy. MRIGlobal obtained its first contract with NASA in 1961 and its first U.S. Arms Control and Disarmament Agency contract in 1964. In the 1970s, the organization began working for the U.S. Environmental Protection Agency developing tests to detect and measure pollutants. Expansion and growth continued in

1560-654: The malaria parasite and is rugged enough for developing countries. But despite these advances in genome analysis, in 2013 infections are still more often identified by other means—their proteome, bacteriophage , or chromatographic profile. Molecular diagnostics are also used to understand the specific strain of the pathogen—for example by detecting which drug resistance genes it possesses—and hence which therapies to avoid. In addition, assays based on metagenomic next generation sequencing can be implemented to identify pathogenic organisms without bias. A patient's genome may include an inherited or random mutation which affects

1625-419: The proteome and the genome . High-throughput protein arrays can use complementary DNA or antibodies to bind and hence can detect many different proteins in parallel. Molecular diagnostic tests vary widely in sensitivity, turn around time, cost, coverage and regulatory approval. They also vary in the level of validation applied in the laboratories using them. Hence, robust local validation in accordance with

1690-478: The variance (or standard deviation) of asset prices. More recent risk measures include value at risk . Because investors are generally risk averse , investments with greater inherent risk must promise higher expected returns. Financial risk management uses financial instruments to manage exposure to risk. It includes the use of a hedge to offset risks by adopting a position in an opposing market or investment. In financial audit , audit risk refers to

1755-465: The 1980s, the phrase was used in the names of companies such as Molecular Diagnostics Incorporated and Bethseda Research Laboratories Molecular Diagnostics . During the 1990s, the identification of newly discovered genes and new techniques for DNA sequencing led to the appearance of a distinct field of molecular and genomic laboratory medicine; in 1995, the Association for Molecular Pathology (AMP)

1820-757: The 1980s. In 1982, a venture group was created to commercialize MRIGlobal’s inventions. Major projects included engineering lightweight thermoelectric cooling devices for U.S. Army aircraft. This technology earned an R&D 100 Award, and was used in Operation Desert Storm to keep flight personnel cool while operating in warm climates. Throughout the next two decades, MRIGlobal expanded its operations, adding locations in Palm Bay, Florida, in 1999; Rockville, Maryland, in 2002; and Frederick, Maryland, in 2003. In January 2015, MRIGlobal powered up their first online detection database, CBRNE Tech Index. On March 1, 2011,

1885-542: The 3' end of primer. Many different companies have developed diagnostics tests based on ARMS PCR primers. For instance, Qiagen therascreen, Roche cobas and Biomerieux THxID have developed FDA approved PCR tests for detecting lung, colon cancer and metastatic melanoma mutations in the KRAS, EGFR and BRAF genes. Their IVD kits were basically validated on genomic DNA extracted from FFPE tissue. There are also microarrays that utilize hybridization mechanism to diagnose cancer. More than

1950-515: The ColoGuard test may be used to screen people over 55 years old for colorectal cancer . Cancer is a longtime-scale disease with various progression steps, molecular diagnostics tools can be used for prognosis of cancer progression. For example, the OncoType Dx test by Genomic Health can estimate risk of breast cancer. Their technology can inform patients to seek chemotherapy when necessary by examining

2015-411: The DNA test must be specific enough to detect mutations at variant allele frequencies of less than 0.1%. Currently, by optimizing the traditional PCR, there's a new invention, amplification-refractory mutation system (ARMS) is a method for detecting DNA sequence variants in cancer. The principle behind ARMS is that the enzymatic extension activity of DNA polymerases is highly sensitive to mismatches near

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2080-504: The Midwest Research Institute was renamed MRIGlobal to reflect its expanded focus. In 2014, MRIGlobal launched CBRNE Tech Index, a comprehensive database of Chemical, Biological, Radiological, Nuclear, and Explosive (CBRNE) detection equipment. Source: 39°02′17″N 94°34′53″W  /  39.038111°N 94.581251°W  / 39.038111; -94.581251 Molecular diagnostics Molecular diagnostics

2145-552: The Next Generation Sequencing (NGS). By utilizing DNA and RNA sequencing to do cancer diagnostics, technology in the field of molecular diagnostics tools will develop better. Although NGS throughput and price have dramatically been reduced over the past 10 years by roughly 100-fold, we remain at least 6 orders of magnitude away from performing deep sequencing at a whole genome level. Currently, Ion Torrent developed some NGS panels based on translational AmpliSeq, for example,

2210-621: The Oncomine Comprehensive Assay. They are focusing on utilizing deep sequencing of cancer-related genes to detect rare sequence variants. Molecular diagnostics tool can be used for cancer risk assessment. For example, the BRCA1/2 test by Myriad Genetics assesses women for lifetime risk of breast cancer. Also, some cancers are not always employed with clear symptoms. It is useful to analyze people when they do not show obvious symptoms and thus can detect cancer at early stages. For example,

2275-477: The RNA expression levels in breast cancer biopsy tissue. With rising government support in DNA molecular diagnostics, it is expected that an increasing number of clinical DNA detection assays for cancers will become available soon. Currently, research in cancer diagnostics are developing fast with goals for lower cost, less time consumption and simpler methods for doctors and patients. Risk In simple terms, risk

2340-563: The United States. Laboratory Information Management Systems help by tracking these processes. Regulation applies to both staff and supplies. As of 2012 , twelve US states require molecular pathologists to be licensed; several boards such as the American Board of Medical Genetics and the American Board of Pathology certify technologists, supervisors, and laboratory directors. Automation and sample barcoding maximise throughput and reduce

2405-533: The anti-clotting agent Clopidogrel , into their active forms. Some patients possess polymorphisms in specific places on the 2C19 gene that make poor metabolisers of those drugs; physicians can test for these polymorphisms and find out whether the drugs will be fully effective for that patient. Advances in molecular biology have helped show that some syndromes that were previously classed as a single disease are actually multiple subtypes with entirely different causes and treatments. Molecular diagnostics can help diagnose

2470-448: The benefit of government , industry, and the public. Source: Founded in 1944 during World War II as Midwest Research Institute, the organization's initial mission was to find a way to convert the ammonium nitrate military ordnance plants in Galena, Kansas , Parsons, Kansas , DeSoto, Kansas and El Dorado, Arkansas to peaceful uses of creating fertilizer . Among the nine founders

2535-441: The breast cancer recurrence risk by profiling the expression of 70 genes related to breast cancer; Autogenomics INFNITI CYP2C19 assay can profile genetic polymorphisms, whose impacts on therapeutic response to antidepressants are great; and Affymetrix's CytoScan Dx can evaluate intellectual disabilities and congenital disorders by analyzing chromosomal mutation. In the future, the diagnostic tools for cancer will likely to focus on

2600-408: The cancer and to choose the best therapy for their patients. As of 2010, assays that incorporate an array of antibodies against specific protein marker molecules are an emerging technology; there are hopes for these multiplex assays that could measure many markers at once. Other potential future biomarkers include micro RNA molecules , which cancerous cells express more of than healthy ones. Cancer

2665-619: The clinic and into the office or home. The clinical laboratory requires high standards of reliability; diagnostics may require accreditation or fall under medical device regulations. As of 2011 , some US clinical laboratories nevertheless used assays sold for "research use only". Laboratory processes need to adhere to regulations, such as the Clinical Laboratory Improvement Amendments , Health Insurance Portability and Accountability Act , Good Laboratory Practice , and Food and Drug Administration specifications in

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2730-711: The common methods of management, the measurements of risk and even the definition of risk differ in different practice areas. This section provides links to more detailed articles on these areas. Business risks arise from uncertainty about the profit of a commercial business due to unwanted events such as changes in tastes, changing preferences of consumers, strikes, increased competition, changes in government policy, obsolescence etc. Business risks are controlled using techniques of risk management . In many cases they may be managed by intuitive steps to prevent or mitigate risks, by following regulations or standards of good practice, or by insurance . Enterprise risk management includes

2795-452: The compromise of organizational assets i.e. the unauthorized use, loss, damage, disclosure or modification of organizational assets for the profit, personal interest or political interests of individuals, groups or other entities." Security risk management involves protection of assets from harm caused by deliberate acts. Risk is ubiquitous in all areas of life and we all manage these risks, consciously or intuitively, whether we are managing

2860-432: The context of public health , risk assessment is the process of characterizing the nature and likelihood of a harmful effect to individuals or populations from certain human activities. Health risk assessment can be mostly qualitative or can include statistical estimates of probabilities for specific populations. A health risk assessment (also referred to as a health risk appraisal and health & well-being assessment)

2925-532: The earliest use of the word in English (in the spelling of risque from its French original, 'risque') as of 1621, and the spelling as risk from 1655. While including several other definitions, the OED 3rd edition defines risk as: (Exposure to) the possibility of loss, injury, or other adverse or unwelcome circumstance; a chance or situation involving such a possibility. The Cambridge Advanced Learner's Dictionary gives

2990-414: The importance of different adverse effects in a particular situation. The Society for Risk Analysis concludes that "experience has shown that to agree on one unified set of definitions is not realistic". The solution is "to allow for different perspectives on fundamental concepts and make a distinction between overall qualitative definitions and their associated measurements." The understanding of risk,

3055-409: The late twentieth century, as did its clinical application. In 1980, Yuet Wai Kan et al . suggested a prenatal genetic test for Thalassemia that did not rely upon DNA sequencing —then in its infancy—but on restriction enzymes that cut DNA where they recognised specific short sequences, creating different lengths of DNA strand depending on which allele (genetic variation) the fetus possessed. In

3120-411: The latter's patents regarding two genes, BRCA1 , BRCA2 , which are associated with breast cancer. In 2013, the U.S. Supreme Court partially agreed , ruling that a naturally occurring gene sequence could not be patented. The industrialisation of molecular biology assay tools has made it practical to use them in clinics. Miniaturisation into a single handheld device can bring medical diagnostics into

3185-444: The local environment. Finance is concerned with money management and acquiring funds. Financial risk arises from uncertainty about financial returns. It includes market risk , credit risk , liquidity risk and operational risk . In finance, risk is the possibility that the actual return on an investment will be different from its expected return. This includes not only " downside risk " (returns below expectations, including

3250-469: The methods and processes used by organizations to manage risks and seize opportunities related to the achievement of their objectives. Economics is concerned with the production, distribution and consumption of goods and services. Economic risk arises from uncertainty about economic outcomes. For example, economic risk may be the chance that macroeconomic conditions like exchange rates, government regulation, or political stability will affect an investment or

3315-527: The methods of assessment and management, the descriptions of risk and even the definitions of risk differ in different practice areas ( business , economics , environment , finance , information technology , health , insurance , safety , security etc). This article provides links to more detailed articles on these areas. The international standard for risk management, ISO 31000 , provides principles and general guidelines on managing risks faced by organizations . The Oxford English Dictionary (OED) cites

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3380-403: The possibility of error or contamination during manual handling and results reporting. Single devices to do the assay from beginning to end are now available. Molecular diagnostics uses in vitro biological assays such as PCR- ELISA or Fluorescence in situ hybridization . The assay detects a molecule, often in low concentrations, that is a marker of disease or risk in a sample taken from

3445-425: The possibility of losing some or all of the original investment) but also "upside risk" (returns that exceed expectations). In Knight's definition, risk is often defined as quantifiable uncertainty about gains and losses. This contrasts with Knightian uncertainty , which cannot be quantified. Financial risk modeling determines the aggregate risk in a financial portfolio. Modern portfolio theory measures risk using

3510-440: The potential that an audit report may fail to detect material misstatement either due to error or fraud. Health risks arise from disease and other biological hazards . Epidemiology is the study and analysis of the distribution, patterns and determinants of health and disease. It is a cornerstone of public health , and shapes policy decisions by identifying risk factors for disease and targets for preventive healthcare . In

3575-455: The probability of developing a disease in the future. For example, Lynch syndrome is a genetic disease that predisposes patients to colorectal and other cancers; early detection can lead to close monitoring that improves the patient's chances of a good outcome. Cardiovascular risk is indicated by biological markers and screening can measure the risk that a child will be born with a genetic disease such as Cystic fibrosis . Genetic testing

3640-485: The quantity of target sequence. Detection of sequence variations using PCR typically involves the design and use oligonucleotide reagents that amplify the variant of interest more efficiently than wildtype sequence. PCR is currently the most widely used method for detection of DNA sequences. The detection of the marker might use real time PCR, direct sequencing, microarray chips —prefabricated chips that test many markers at once, or MALDI-TOF The same principle applies to

3705-417: The regulatory requirements and use of appropriate controls is required especially where the result may be used to inform a patient treatment decision. Benefits Conventional prenatal tests for chromosomal abnormalities such as Down Syndrome rely on analysing the number and appearance of the chromosomes—the karyotype . Molecular diagnostics tests such as microarray comparative genomic hybridisation test

3770-509: The specific single nucleotide polymorphism causing an individual's disease. As the commercial application of molecular diagnostics has become more important, so has the debate about patenting of the genetic discoveries at its heart . In 1998, the European Union 's Directive 98/44/ECclarified that patents on DNA sequences were allowable. In 2010 in the US, AMP sued Myriad Genetics to challenge

3835-516: The specifics of the patient and their disease, molecular diagnostics offers the prospect of personalised medicine . These tests are useful in a range of medical specialties , including infectious disease , oncology , human leucocyte antigen typing (which investigates and predicts immune function ), coagulation , and pharmacogenomics —the genetic prediction of which drugs will work best. They overlap with clinical chemistry (medical tests on bodily fluids). The field of molecular biology grew in

3900-446: The subtype—for example of infections and cancers—or the genetic analysis of a disease with an inherited component, such as Silver-Russell syndrome . Molecular diagnostics are used to identify infectious diseases such as chlamydia , influenza virus and tuberculosis ; or specific strains such as H1N1 virus or SARS-CoV-2 . Genetic identification can be swift; for example a loop-mediated isothermal amplification test diagnoses

3965-446: The target sequence(s) in the patient sample. PCR is a method that a template DNA is amplified using synthetic primers, a DNA polymerase, and dNTPs. The mixture is cycled between at least 2 temperatures: a high temperature for denaturing double-stranded DNA into single-stranded molecules and a low temperature for the primer to hybridize to the template and for the polymerase to extend the primer. Each temperature cycle theoretically doubles

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4030-422: The term to negative impacts ("downside risks"), while others also include positive impacts ("upside risks"). Some resolve these differences by arguing that the definition of risk is subjective. For example: No definition is advanced as the correct one, because there is no one definition that is suitable for all problems. Rather, the choice of definition is a political one, expressing someone's views regarding

4095-423: The uncontrolled release of radiation or a toxic chemical may have immediate short-term safety consequences, more protracted health impacts, and much longer-term environmental impacts . Events such as Chernobyl , for example, caused immediate deaths, and in the longer term, deaths from cancers, and left a lasting environmental impact leading to birth defects , impacts on wildlife, etc. Information technology (IT)

4160-739: Was Kenneth A. Spencer who would make a fortune from the Jayhawk Plant in Galena. Spencer would be chairman of the Institute from 1954 to 1957, and donated money for the Kenneth A. Spencer Laboratories Building and the Spencer Auditorium at MRIGlobal. MRIGlobal was located first in the former Westport, Missouri City Hall at 40th Terrace and Pennsylvania. That building was torn down in 1955 at which time MRIGlobal moved into its Kansas City headquarters facing

4225-659: Was formed to give it structure. In 1999, the AMP co-founded The Journal of Medical Diagnostics . Informa Healthcare launched Expert Reviews in Medical Diagnostics in 2001. From 2002 onwards, the HapMap Project aggregated information on the one-letter genetic differences that recur in the human population—the single nucleotide polymorphisms —and their relationship with disease. In 2012, molecular diagnostic techniques for Thalassemia use genetic hybridization tests to identify

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