259:, the mutation is prognostic since its presence in the patient endure the same outcome regardless of the treatment method used. Women who had the PIK3CA mutation before treatment, had the lowest average survival rate. The decline in the groups containing the mutant occurred quicker and in a much steeper decline. The independent nature of the prognostic factor allows researcher to study the disease or condition in its natural state. This makes it easier to observe these abnormal biological processes and speculate on how to correct them. Prognostic factors are often used in combination with predictive variables in therapeutics studies, to examine how effective different treatments are in curing specific diseases or cancer. As opposed to predictive biomarkers, prognostic do not rely on any explanatory variables, thus allowing for independent examination of the underlying disease or condition.
617:
concentrations in water, sediments, and aquatic organisms. The methods used to identify these chemical compounds were chromatography, spectrophotometry, electrochemistry, and radiochemistry. Although these methods were successful in elucidating the chemical makeup and concentrations present in the environment of the contaminants and the compounds in question, the tests did not provide data that was informative on the impact of a certain pollutant or chemical on a living organism or ecosystem. It was proposed that characterizing biomarkers could create a warning system to check in on the well being of a population or an ecosystem before a pollutant or compound could wreak havoc on the system. Now, due to the development of biomarker studies, biomarkers can be used and applied in the fields of human medicine and in the detection of diseases.
84:
biomarkers situated at the interface of pathology-specific molecular process architecture and drug mechanism of action promise capturing aspects allowing assessment of an individual treatment response. This offers a dual approach to both seeing trends in retrospective studies and using biomarkers to predict outcomes. For example, in metastatic colorectal cancer predictive biomarkers can serve as a way of evaluating and improving patient survival rates and in the individual case by case scenario, they can serve as a way of sparing patients from needless toxicity that arises from cancer treatment plans.
242:(MCI). One major current use of digital biomarkers involves keeping track of regular brain activity. Specific neural indicators can be measured by devices to evaluate patients for any neuro abnormalities. The data collected can determine the patients disease probability or condition. While patients carryout everyday tasks (IADL), computers are using machine learning to observe and detect any deviation from normal behavior. These markers are used as signs or indicators of cognitive decline.
100:
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that can be measured, depending on the contaminant or the response in question. There are also a variety of contaminants within water bodies. To analyze the impact of a pollutant on an organism, the biomarker must respond to a specific contaminant within a specific time frame or at a certain concentration. The biomarkers used to detect pollution in aquatic organisms can be enzymatic or non-enzymatic.
2959:
580:, raised the issue of using organochlorine pesticides and discussed the possible negative effects that said pesticides have on living organisms. Her book raised ethical issues against chemical corporations that were controlling the general reception of the effect of pesticides on the environment, which pioneered the need for
325:
The field of biomarker research is also expanding to include a combinatorial approach to identifying biomarkers from multiple sources. Combining biomarkers from various data allows for the possibility of developing panels that evaluate treatment response based on many biomarkers at a single time. One
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research. Most research to date uses biomarkers that are easily measured, including weight, blood pressure, and glucose; these biomarkers may reflect the impacts of diet, physical activity, and smoking reduction. However, the methods by which feedback from biomarkers are used in intervention research
567:
on the bottoms of streams, which is where many contaminants settle. These organisms have high exposure to the contamination, which makes them good study species when detecting pollutant concentrations and pollution impacts on an ecosystem. There are a variety of biomarkers within an aquatic organism
632:
In 1990, McCarthy and
Shugart defined biomarkers as, "measurements at the molecular, biochemical, or cellular level in either wild populations from contaminated habitats or in organisms experimentally exposed to pollutants that indicate that the organism has been exposed to toxic chemicals, and the
405:
Ensuring that all of the participants that are included each step of the project (i.e. planning, implementation, and the compilation of the results) are provided with the protection of ethical principles that are put in place prior to beginning the project. These ethical protections should not only
640:
In 1996, Van Gestel and Van
Brummelen attempted to redefine biomarkers to unambiguously differentiate a biomarker from a bioindicator. According to Van Gestel and Van Brummelen, a biomarker by definition should be used only to describe sublethal biochemical changes resulting from individual
317:
In reference to the clinical toolset, only two predictive biomarkers are implemented clinically in the case of metastatic colorectal cancer. In this case, the lack of data beyond retrospective studies and successful biomarker-driven approaches may be a factor in using biomarker studies due to the
74:
Biomarkers used in the medical field, are a part of a relatively new clinical toolset categorized by their clinical applications. The four main classes are molecular, physiologic, histologic and radiographic biomarkers. All four types of biomarkers have a clinical role in narrowing or guiding
279:
where reliable dietary information are required. A nutritional biomarker can be any specimen that reflects intake of dietary constituents and is sufficiently specific. Many biomarkers are derived from compounds found in foods, such as sugar or phytochemicals, or combinations thereof using a
83:
Predictive molecular, cellular, or imaging biomarkers that pass validation can serve as a method of predicting clinical outcomes. Predictive biomarkers are used to help optimize ideal treatments, and often indicate the likelihood of benefiting from a specific therapy. For example, molecular
616:
The widespread use of the term "biomarker" dates back to as early as 1980. The manner in which the environment was monitored and studied near the end of the 1980s was still mainly reliant on the study of chemical substances that were considered dangerous or toxic when found in moderate
531:. The oil affected many surrounding areas. Samples of the crude oil were collected in the various regions where it had spread and compared to samples that were unreleased in an attempt to distinguish between the spilled oil and the petrogenic background present in the spill area.
330:. In this example, a relatively low cost sequencing pipeline was shown to be able to detect low frequency mutations within tumor-associated cells. This highlights the general snapshot capability of mitochondrial DNA-based biomarkers in capturing heterogeneity amongst individuals.
662:
De Kock and Kramer developed the concept of active biomonitoring in 1994. Active biomonitoring is a comparison of the chemical/biological properties of a sample that has been relocated to a new environment that contains different conditions than its original environment.
636:
In 1994, Depledge defined a biomarker as, "a biochemical, cellular, physiological or behavioral change which can be measured in body tissues or fluids or at the level of the whole organism that reveals the exposure at/or the effects of one or more chemical
1135:"Thorough overview of ubiquitin C-terminal hydrolase-L1 and glial fibrillary acidic protein as tandem biomarkers cleared by US Food and Drug Administration for the evaluation of intracranial injuries among patients with traumatic brain injury"
648:
Biomarkers
Definitions Working Group defined a biomarker as "a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic
300:
Biomarkers for precision medicine are a part of a relatively new behavioral and clinical toolset. In terms of the behavioral toolset, biomarkers are increasingly being used to motivate health behavior change, particularly in
406:
protect the participants in the study, but also the non participants, researchers, sponsors, regulators, and all other persons or groups involved in the study. Some ethical protections could include but are not limited to:
250:
A prognostic biomarker provides information about the patients overall outcome, regardless of any treatment or therapeutic intervention. One example of a prognostic biomarkers in clinical research, is the use of mutated
326:
such area of expanding research in multiple-factor biomarkers is mitochondrial DNA sequencing. Mutations in mitochondrial DNA have been shown to correlate to risk, progression, and treatment response of head and neck
87:
Common examples of predictive biomarkers are genes such as ER, PR and HER2/neu in breast cancer, BCR-ABL fusion protein in chronic myeloid leukaemia, c-KIT mutations in GIST tumours and EGFR1 mutations in NSCLC.
126:. More specifically, a biomarker indicates a change in expression or state of a protein that correlates with the risk or progression of a disease, or with the susceptibility of the disease to a given treatment.
133:(PSA). This marker can be measured as a proxy of prostate size with rapid changes potentially indicating cancer. The most extreme case would be to detect mutant proteins as cancer specific biomarkers through
652:
In 2000, De
Lafontaine defined the term biomarker as a "biochemical and/or physiological change(s) in organisms exposed to contaminants, and thus represent initial responses to environmental perturbation and
354:
validation of these benefits. The biologic rationale of a study must be assessed on a small scale before any large scale studies can occur. Many candidates must be tested to select the most relevant ones.
2882:
Gagné F, Blaise C, Costan G, Gagnon P, Chan HM (August 2000). "Biomarkers in zebra mussels (Dreissena polymorpha) for the assessment and monitoring of water quality of the St
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629:
In 1987, biological markers were defined as "indicators signaling events in biological systems or samples" that could be classified into three categories: exposure, effect and susceptibility markers.
256:
1715:
Makarewicz CA, Sealy J (April 1, 2015). "Dietary reconstruction, mobility, and the analysis of ancient skeletal tissues: Expanding the prospects of stable isotope research in archaeology".
363:
One of the most important steps, it serves to identify specific characteristics of the candidate biomarker before developing a routine test. Several parameters are considered including:
96:
Diagnostic biomarkers that meet a burden of proof can serve a role in narrowing down diagnosis. This can lead to diagnosis that are significantly more specific to individual patients.
832:
Siderowf A, Aarsland D, Mollenhauer B, Goldman JG, Ravina B (April 2018). "Biomarkers for cognitive impairment in Lewy body disorders: Status and relevance for clinical trials".
219:), which can be seen as next-generation digital biomarkers. Collecting and tracking digital biomarkers have become more easily available with the advancement of smartphones and
2032:"Somatic mitochondrial mutation discovery using ultra-deep sequencing of the mitochondrial genome reveals spatial tumor heterogeneity in head and neck squamous cell carcinoma"
394:
This optimizes the validated protocol for routine use, including analysis of the critical points by scanning the entire procedure to identify and control the potential risks.
402:
In 1997 the
National Institute of Health suggested a need for guidelines and legislation development that would regulate the ethical dimensions of biomarker studies.
152:(GFAP) to aid in the diagnosis of the presence of cranial lesion(s) among moderate to mild TBI patients that is(are) otherwise only diagnosable with the use of a
416:
Access to participation opportunities independent of race, socio-economic status, gender, sexuality, etc. (within the range allowed by the experimental protocol)
519:. Biomarkers were used in the geo-chemical investigation of an oil spill in the San Francisco Bay, California in 1988. On April 22–23 around 400,000 gallons of
750:
Hirsch MS, Watkins J (May 2020). "A Comprehensive Review of
Biomarker Use in the Gynecologic Tract Including Differential Diagnoses and Diagnostic Pitfalls".
2993:
1335:"Detection of atrial fibrillation with a smartphone camera: first prospective, international, two-centre, clinical validation study (DETECT AF PRO)"
1672:
Jenab M, Slimani N, Bictash M, Ferrari P, Bingham SA (June 2009). "Biomarkers in nutritional epidemiology: applications, needs and new horizons".
145:
115:
A biomarker can be a traceable substance that is introduced into an organism as a means to examine organ function or other aspects of health.
2758:
2725:
2517:
2469:
2317:"Combining biomarker and community approaches using benthic macroinvertebrates can improve the assessment of the ecological status of rivers"
2227:
1604:
2782:
Van Gestel CA, Van
Brummelen TC (August 1996). "Incorporation of the biomarker concept in ecotoxicology calls for a redefinition of terms".
796:
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of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal
2925:
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2623:
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2942:
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or is associated with susceptibility to disease. They can be used to create genetic maps of whatever organism is being studied.
149:
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Oldenhuis CN, Oosting SF, Gietema JA, de Vries EG (May 2008). "Prognostic versus predictive value of biomarkers in oncology".
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studies. Ecotoxicologial studies could be considered the precursors to biomarker studies. Biomarkers are used to indicate an
2095:
The early detection research network :translational research to identify early cancer and cancer risk : initial report
645:
2270:"Testing sediment biological effects with the freshwater amphipod Hyalella azteca: the gap between laboratory and nature"
342:(EDRN) compiled a list of seven criteria by which biomarkers can be assessed in order to streamline clinical validation.
2998:
1544:"Digital Biomarkers for the Early Detection of Mild Cognitive Impairment: Artificial Intelligence Meets Virtual Reality"
172:
168:
134:
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2118:
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within the samples. Variations in the concentration of constituents of the crude oil samples and sediments were found.
215:. Novel non-invasive, molecular digital biomarkers are increasingly available recorded by e.g. on-skin sweat analysis (
1599:. Studies in Neuroscience, Psychology and Behavioral Economics (SNPBE). Cham, Switzerland: Springer Cham. p. 14.
2407:"The effects of carbamazepine on macroinvertebrate species: Comparing bivalves and polychaetes biochemical responses"
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227:(PD), for example, finger tapping a mobile phone via counting apps have been used as a method of (self-)evaluating
22:
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239:
130:
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It can also be a substance whose detection indicates a particular disease state, for example, the presence of an
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Previously used to identify the specific characteristics of the biomarker, this step is essential for doing an
272:
53:
2119:"Proof-of-concept study of biomarker development in mice provides a roadmap for a similar approach in humans"
327:
235:
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treatment decisions and follow a sub-categorization of being either predictive, prognostic, or diagnostic.
2974:
2741:
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1981:
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is a molecule that allows the detection and isolation of a particular cell type (for example, the protein
306:
224:
141:
516:
104:
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Biomarkers are being used to identify the effects of water contamination on aquatic organisms.
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Nutritional biomarkers (biochemical markers of intake) are used to estimate dietary intake in
176:
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171:. Biomarkers for precision oncology are typically utilized in the molecular diagnostics of
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422:
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203:. So far, digital biomarkers have been focusing on monitoring vital parameters such as
199:
Digital biomarkers are a novel emerging field of biomarkers, mostly collected by smart
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can be measured to determine exactly when an attack occurred and how severe it was.
2145:
825:
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2047:
1384:"Automated assessment of psychiatric disorders using speech: A systematic review"
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indicating the existence, past or present, of living organisms. In the fields of
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435:
Transparency and recognition of health and legal risks involved in participation
285:
276:
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144:(TBI) blood-based biomarker test consisted of measuring the levels of neuronal
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515:. The term biomarker is also used to describe biological involvement in the
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220:
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200:
123:
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Geochemical investigation of an oil spill in San Francisco Bay, California
1763:
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and in organisms. The biomarker may be an external substance itself (e.g.
597:
564:
500:
464:
302:
188:
160:
119:
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563:macro-invertebrates reside in the
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467:, a biomarker (identified as
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2851:10.1097/COH.0b013e32833ed177
2712:. CRC Press. pp. 3–14.
2637:10.1016/0002-9394(60)91653-6
2431:10.1016/j.watres.2015.08.003
2048:10.1016/j.canlet.2019.12.006
1869:O'Brien DM (July 17, 2015).
1756:IARC Scientific Publications
1634:Journal of Clinical Oncology
1628:Ballman KV (November 2015).
764:10.1097/PAP.0000000000000238
169:signal transduction pathways
159:Another example is KRAS, an
135:selected reaction monitoring
217:internet-enabled Sudorology
3022:
2333:10.1007/s10750-019-03991-7
2162:10.1016/j.trac.2017.12.015
1875:Annual Review of Nutrition
1022:10.1016/j.ejca.2008.03.006
1010:European Journal of Cancer
552:
546:
492:
486:
67:
28:In biomedical contexts, a
23:Biomarker (disambiguation)
20:
2582:Porter KA (August 1957).
2370:(1): 1. August 15, 2004.
2220:10.1007/978-0-387-79251-4
1737:10.1016/j.jas.2015.02.035
1686:10.1007/s00439-009-0662-5
1288:Frontiers in Neuroscience
1202:10.1007/s40291-013-0077-9
1053:National Cancer Institute
592:which are present in the
318:attrition of subjects in
240:mild cognitive impairment
131:prostate-specific antigen
2751:10.1201/9780367813703-20
1818:Tasevska N (July 2015).
1783:The Journal of Nutrition
1647:10.1200/JCO.2015.63.3651
1561:10.3389/fnhum.2020.00245
1301:10.3389/fnins.2017.00555
641:exposure to xenobiotics.
390:Protocol standardization
273:nutritional epidemiology
271:research, in particular
173:chronic myeloid leukemia
54:therapeutic intervention
2935:10.1002/047147844x.wq16
2718:10.1201/9781351070263-2
2533:Aronson JK (May 2005).
2255:2027/uc1.31210025025220
2104:2027/mdp.39015049497442
1351:10.1093/europace/euy176
1101:10.1073/pnas.1019203108
893:10.1602/neurorx.1.2.182
875:Mayeux R (April 2004).
810:10.1067/mcp.2001.113989
517:generation of petroleum
328:squamous cell carcinoma
307:cardiovascular diseases
236:artificial intelligence
2835:"What are biomarkers?"
2245:Hostettler FD (1991).
962:JCO Precision Oncology
537:aliphatic hydrocarbons
142:traumatic brain injury
112:
107:a number of different
2669:: 3–9. October 1987.
2502:Ecological Biomarkers
1986:Biological Psychiatry
1796:10.1093/jn/133.3.873S
290:stable isotope ratios
102:
658:Active biomonitoring
588:to or the effect of
458:embryonic stem cells
419:Scientific integrity
167:involved in several
70:Biomarker (medicine)
42:biological processes
21:For other uses, see
2999:Biology terminology
2896:2000AqTox..50...51D
2796:1996Ecotx...5..217V
2423:2015WatRe..85..137F
2376:2004ScTEn.329....1.
2286:2004Chmsp..57.1713W
1729:2015JArSc..56..146M
1092:2011PNAS..108.2444W
974:10.1200/PO.18.00260
679:Biomarker discovery
225:Parkinson's disease
2927:Water Encyclopedia
2884:Aquatic Toxicology
2804:10.1007/bf00118992
1500:10.1002/mdc3.12246
1439:Digital Biomarkers
1239:Digital Biomarkers
1055:. February 2, 2011
834:Movement Disorders
685:Biomarker Insights
525:San Joaquin Valley
413:of the participant
140:An example is the
113:
109:cardiac biomarkers
36:, is a measurable
2760:978-0-367-81370-3
2727:978-1-351-07026-3
2676:10.1289/ehp.87743
2519:978-0-429-11149-5
2471:978-0-14-118494-4
2464:. Penguin Books.
2460:Carson R (2000).
2280:(11): 1713–1724.
2228:978-0-387-79250-7
2196:. NIH publication
1992:(11): 1001–1005.
1837:10.3390/nu7075255
1640:(33): 3968–3971.
1606:978-3-030-31620-4
1451:10.1159/000504387
1251:10.1159/000502000
846:10.1002/mds.27355
725:Sponge biomarkers
705:Imaging biomarker
688: – a journal
529:Shell Oil Company
58:scientific fields
34:biological marker
3011:
2961:
2960:
2949:
2948:
2922:
2916:
2915:
2879:
2873:
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2830:
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2265:
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2231:
2222:Copyright: 2009
2212:
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2091:
2074:
2073:
2059:
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2018:
2017:
1977:
1971:
1970:
1960:
1942:
1918:
1909:
1908:
1898:
1866:
1860:
1859:
1849:
1839:
1830:(7): 5816–5833.
1815:
1809:
1808:
1798:
1789:(3): 873S–874S.
1774:
1768:
1767:
1758:(142): 103–126.
1747:
1741:
1740:
1712:
1706:
1705:
1680:(5–6): 507–525.
1669:
1660:
1659:
1649:
1625:
1619:
1618:
1590:
1584:
1583:
1573:
1563:
1539:
1530:
1529:
1519:
1479:
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1462:
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1423:
1413:
1403:
1401:10.1002/lio2.354
1379:
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1362:
1330:
1324:
1323:
1313:
1303:
1279:
1273:
1272:
1262:
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1224:
1223:
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1181:
1175:
1174:
1164:
1154:
1152:10.1002/ams2.622
1130:
1124:
1123:
1113:
1103:
1086:(6): 2444–2449.
1071:
1065:
1064:
1062:
1060:
1045:
1034:
1033:
1005:
996:
995:
985:
953:
944:
943:
941:
929:
923:
922:
912:
872:
866:
865:
829:
793:
784:
783:
747:
715:Molecular marker
582:ecotoxicological
574:, the author of
411:Informed consent
346:Proof of concept
122:may indicate an
3021:
3020:
3014:
3013:
3012:
3010:
3009:
3008:
2984:
2983:
2982:
2981:
2980:
2962:
2958:
2953:
2952:
2945:
2924:
2923:
2919:
2881:
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2876:
2832:
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2827:
2781:
2780:
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2740:
2739:
2735:
2728:
2707:
2706:
2702:
2657:
2656:
2652:
2622:
2621:
2617:
2581:
2580:
2576:
2532:
2531:
2527:
2520:
2499:
2498:
2487:
2472:
2459:
2458:
2454:
2404:
2403:
2399:
2361:
2360:
2356:
2314:
2313:
2309:
2267:
2266:
2262:
2244:
2243:
2234:
2213:
2209:
2199:
2197:
2188:
2187:
2183:
2143:
2142:
2138:
2128:
2126:
2125:. July 19, 2011
2117:
2116:
2112:
2093:
2092:
2077:
2029:
2028:
2021:
1979:
1978:
1974:
1920:
1919:
1912:
1868:
1867:
1863:
1817:
1816:
1812:
1776:
1775:
1771:
1749:
1748:
1744:
1714:
1713:
1709:
1671:
1670:
1663:
1627:
1626:
1622:
1607:
1592:
1591:
1587:
1541:
1540:
1533:
1481:
1480:
1476:
1432:
1431:
1427:
1381:
1380:
1376:
1332:
1331:
1327:
1281:
1280:
1276:
1232:
1231:
1227:
1183:
1182:
1178:
1139:Acute Med. Surg
1132:
1131:
1127:
1073:
1072:
1068:
1058:
1056:
1047:
1046:
1037:
1007:
1006:
999:
955:
954:
947:
931:
930:
926:
874:
873:
869:
831:
795:
794:
787:
749:
748:
744:
739:
734:
669:
660:
653:contamination".
623:
614:
557:
551:
545:
497:
491:
485:
442:
423:Confidentiality
400:
392:
379:reproducibility
361:
348:
336:
320:clinical trials
298:
265:
248:
197:
187:cancer, and in
163:that encodes a
94:
81:
72:
66:
52:responses to a
26:
17:
12:
11:
5:
3019:
3018:
3015:
3007:
3006:
3001:
2996:
2986:
2985:
2963:
2956:
2955:
2954:
2951:
2950:
2943:
2917:
2890:(1–2): 51–71.
2874:
2845:(6): 463–466.
2825:
2790:(4): 217–225.
2774:
2759:
2733:
2726:
2700:
2650:
2631:(3): 513–515.
2615:
2594:(4): 401–412.
2574:
2545:(5): 491–494.
2525:
2518:
2510:10.1201/b13036
2485:
2470:
2452:
2411:Water Research
2397:
2354:
2307:
2260:
2232:
2207:
2181:
2136:
2110:
2075:
2036:Cancer Letters
2019:
1972:
1910:
1881:(1): 565–594.
1861:
1810:
1769:
1742:
1707:
1674:Human Genetics
1661:
1620:
1605:
1585:
1531:
1494:(2): 184–187.
1474:
1445:(3): 155–165.
1425:
1374:
1325:
1274:
1225:
1196:(3): 273–284.
1176:
1125:
1066:
1035:
1016:(7): 946–953.
997:
945:
939:10.1101/573402
924:
887:(2): 182–188.
867:
840:(4): 528–536.
785:
758:(3): 164–192.
741:
740:
738:
735:
733:
732:
727:
722:
720:Saliva testing
717:
712:
707:
702:
697:
689:
681:
676:
670:
668:
665:
659:
656:
655:
654:
650:
649:intervention."
642:
638:
634:
630:
622:
619:
613:
610:
547:Main article:
544:
541:
487:Main article:
484:
481:
469:genetic marker
441:
438:
437:
436:
433:
430:
420:
417:
414:
399:
398:Ethical issues
396:
391:
388:
387:
386:
383:
380:
377:
374:
371:
368:
360:
357:
347:
344:
335:
332:
297:
294:
264:
261:
247:
244:
196:
193:
148:(UCH-L1) and
93:
90:
80:
77:
68:Main article:
65:
62:
48:processes, or
15:
13:
10:
9:
6:
4:
3:
2:
3017:
3016:
3005:
3002:
3000:
2997:
2995:
2992:
2991:
2989:
2978:
2977:
2976:
2970:
2966:
2946:
2944:0-471-47844-X
2940:
2936:
2932:
2928:
2921:
2918:
2913:
2909:
2905:
2901:
2897:
2893:
2889:
2885:
2878:
2875:
2870:
2866:
2861:
2856:
2852:
2848:
2844:
2840:
2836:
2829:
2826:
2821:
2817:
2813:
2809:
2805:
2801:
2797:
2793:
2789:
2785:
2784:Ecotoxicology
2778:
2775:
2770:
2766:
2762:
2756:
2752:
2748:
2744:
2737:
2734:
2729:
2723:
2719:
2715:
2711:
2704:
2701:
2696:
2692:
2687:
2682:
2677:
2672:
2668:
2664:
2660:
2654:
2651:
2646:
2642:
2638:
2634:
2630:
2626:
2619:
2616:
2611:
2607:
2602:
2597:
2593:
2589:
2585:
2578:
2575:
2570:
2566:
2561:
2556:
2552:
2548:
2544:
2540:
2536:
2529:
2526:
2521:
2515:
2511:
2507:
2504:. CRC Press.
2503:
2496:
2494:
2492:
2490:
2486:
2481:
2477:
2473:
2467:
2463:
2462:Silent spring
2456:
2453:
2448:
2444:
2440:
2436:
2432:
2428:
2424:
2420:
2416:
2412:
2408:
2401:
2398:
2393:
2389:
2385:
2381:
2377:
2373:
2369:
2365:
2358:
2355:
2350:
2346:
2342:
2338:
2334:
2330:
2326:
2322:
2321:Hydrobiologia
2318:
2311:
2308:
2303:
2299:
2295:
2291:
2287:
2283:
2279:
2275:
2271:
2264:
2261:
2256:
2252:
2248:
2241:
2239:
2237:
2233:
2229:
2225:
2221:
2217:
2211:
2208:
2195:
2191:
2185:
2182:
2177:
2172:
2167:
2163:
2159:
2155:
2151:
2147:
2140:
2137:
2124:
2120:
2114:
2111:
2105:
2100:
2096:
2090:
2088:
2086:
2084:
2082:
2080:
2076:
2071:
2067:
2063:
2058:
2053:
2049:
2045:
2041:
2037:
2033:
2026:
2024:
2020:
2015:
2011:
2007:
2003:
1999:
1995:
1991:
1987:
1983:
1976:
1973:
1968:
1964:
1959:
1954:
1950:
1946:
1941:
1940:10.2196/44359
1936:
1932:
1928:
1924:
1917:
1915:
1911:
1906:
1902:
1897:
1892:
1888:
1884:
1880:
1876:
1872:
1865:
1862:
1857:
1853:
1848:
1843:
1838:
1833:
1829:
1825:
1821:
1814:
1811:
1806:
1802:
1797:
1792:
1788:
1784:
1780:
1773:
1770:
1765:
1761:
1757:
1753:
1746:
1743:
1738:
1734:
1730:
1726:
1722:
1718:
1711:
1708:
1703:
1699:
1695:
1691:
1687:
1683:
1679:
1675:
1668:
1666:
1662:
1657:
1653:
1648:
1643:
1639:
1635:
1631:
1624:
1621:
1616:
1612:
1608:
1602:
1598:
1597:
1589:
1586:
1581:
1577:
1572:
1567:
1562:
1557:
1553:
1549:
1545:
1538:
1536:
1532:
1527:
1523:
1518:
1513:
1509:
1505:
1501:
1497:
1493:
1489:
1485:
1478:
1475:
1470:
1466:
1461:
1456:
1452:
1448:
1444:
1440:
1436:
1429:
1426:
1421:
1417:
1412:
1407:
1402:
1397:
1394:(1): 96–116.
1393:
1389:
1385:
1378:
1375:
1370:
1366:
1361:
1356:
1352:
1348:
1344:
1340:
1336:
1329:
1326:
1321:
1317:
1312:
1307:
1302:
1297:
1293:
1289:
1285:
1278:
1275:
1270:
1266:
1261:
1256:
1252:
1248:
1245:(2): 92–102.
1244:
1240:
1236:
1229:
1226:
1221:
1217:
1212:
1207:
1203:
1199:
1195:
1191:
1187:
1180:
1177:
1172:
1168:
1163:
1158:
1153:
1148:
1144:
1140:
1136:
1129:
1126:
1121:
1117:
1112:
1107:
1102:
1097:
1093:
1089:
1085:
1081:
1077:
1070:
1067:
1054:
1050:
1044:
1042:
1040:
1036:
1031:
1027:
1023:
1019:
1015:
1011:
1004:
1002:
998:
993:
989:
984:
979:
975:
971:
967:
963:
959:
952:
950:
946:
940:
935:
928:
925:
920:
916:
911:
906:
902:
898:
894:
890:
886:
882:
878:
871:
868:
863:
859:
855:
851:
847:
843:
839:
835:
827:
823:
819:
815:
811:
807:
803:
799:
792:
790:
786:
781:
777:
773:
769:
765:
761:
757:
753:
746:
743:
736:
731:
728:
726:
723:
721:
718:
716:
713:
711:
708:
706:
703:
701:
700:Endophenotype
698:
696:
694:
690:
687:
686:
682:
680:
677:
675:
672:
671:
666:
664:
657:
651:
647:
644:In 1998, the
643:
639:
635:
631:
628:
627:
626:
620:
618:
611:
609:
607:
603:
600:particles or
599:
595:
591:
587:
583:
579:
578:
577:Silent Spring
573:
572:Rachel Carson
569:
566:
562:
556:
550:
543:Ecotoxicology
542:
540:
538:
534:
530:
526:
522:
518:
514:
513:biosignatures
510:
506:
502:
496:
490:
482:
480:
478:
474:
470:
466:
461:
459:
455:
451:
447:
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428:
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418:
415:
412:
409:
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403:
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389:
384:
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369:
366:
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345:
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323:
321:
315:
312:
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293:
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278:
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270:
262:
260:
258:
254:
245:
243:
241:
237:
232:
230:
226:
222:
218:
214:
210:
206:
205:accelerometer
202:
194:
192:
190:
186:
182:
178:
174:
170:
166:
162:
157:
156:of the head.
155:
151:
147:
143:
138:
136:
132:
127:
125:
121:
116:
110:
106:
101:
97:
91:
89:
85:
78:
76:
71:
63:
61:
59:
55:
51:
50:pharmacologic
47:
43:
39:
35:
31:
24:
19:
2973:
2972:
2971:profile for
2968:
2926:
2920:
2887:
2883:
2877:
2842:
2838:
2828:
2787:
2783:
2777:
2742:
2736:
2709:
2703:
2666:
2662:
2653:
2628:
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