Clinical Chemistry

Apart from the central beneficial role platelets play in hemostasis, they are also involved in atherothrombotic diseases. Here, we review the current knowledge of platelet intracellular signal transduction pathways involved in platelet adhesion, activation, amplification of the activation signal and aggregation, as well as pathways limiting platelet aggregation. A thorough understanding of these pathways allows explanation of the mechanism of action of existing antiplatelet agents, but also helps to identify targets for novel drug development. Clin Chem Lab Med 2010;48:S3-13.

We measured apolipoproteins (apo) A-I and B by rate immunonephelometry (rate INA) during Phase 1 of the National Health and Nutrition Examination Survey (NHANES) III. We also made the measurements by radial immunodiffusion (RID) in a 20% subset of the samples. Aliquots of this subset were also analyzed in the Northwest Lipid Research Laboratories by fixed-time INA calibrated to the World Health Organization (WHO)-International Federation of Clinical Chemistry (IFCC) First International Reference Materials for Apolipoproteins A-I and B. The CVs for the rate INA and RID measurements were: apoA-I, 4.5-7.7% and 2.5-7.6%, respectively; apoB, 2.3-5.3% and 2.3-6.4%, respectively. In NHANES III, rate INA values (x) can be transformed to WHO-IFCC Reference Material-based values (y) as follows: for apoA-I, y = 0.87x + 251.8 mg/L (r = 0.93, SEslope = 0.13, SEintercept = 17, n = 708); for apoB (mg/L), y = 1.068x + 112.8 mg/L (r = 0.98, SEslope = 0.08, SEintercept = 7, n = 646).

The potential role of stem cells in neoplasia is a subject of recent interest. Three markers of melanocytic stem cells have been described recently. CD166 is expressed on the surface of mesenchymal stem cells and has been found on human melanoma cell lines. CD133 is expressed on the surface of dermal-derived stem cells that are capable of differentiating into neural cells. Nestin is an intermediate filament expressed in the cytoplasm of neuroepithelial stem cells. In this study, we evaluate the expression of these markers and possible differences among banal nevi, primary melanoma, and metastastic melanoma. Tissue microarrays containing normal tissue and 226 melanocytic lesions (71 banal nevi, 71 in situ and invasive melanomas, and 84 metastatic melanomas) were studied by immunohistochemistry using monoclonal antibodies CD166, CD133, and nestin. A significantly greater percentage of melanomas (combined primary and metastatic) contained cells that expressed CD166 (P ¼ 0.005), CD133 (P ¼ 0.003), and nestin (P ¼ 0.03) than banal nevi. Only nestin showed a statistical difference when comparing primary and metastatic melanoma (P ¼ 0.05). A stepwise increase in the proportion of lesions expressing all three markers was observed from banal nevi (2/19) to primary melanomas (8/17) to metastatic melanoma (19/28), P ¼ 0.0005. All cases of metastatic melanoma expressed at least one stem cell marker. The increased expression of CD166, CD133, and nestin in melanoma suggests that progression to malignant melanoma likely involves genetic pathways instrumental to stem cell biology and normal tissue development. Further studies and characterization of these pathways may also reveal new prognostic markers for a disease whose prognosis in advanced stages is dismal.

Orotic acid (ORA) is an important biochemical marker for uridine monophosphate synthase deficiency, an autoso-mal recessive disease characterized by macrocytic hypo-chromic megaloblastic anemia, growth retardation, orotic aciduria, and crystalluria (1). In addition, patients with urea cycle diseases excrete increased amounts of urinary ORA (2). Thus, ORA aciduria is observed in patients with ornithine carbamoylasetransferase deficiency (OCTD), an X-linked disorder, and could reveal heterozygosity after a protein load, and in citrullinemia, argininosuccinic acid-uria, and argininemia (2, 3). Currently there are two widely accepted approaches to the determination of urinary ORA, stable-isotope-dilution gas chromatography–mass spectrometry (GC/MS), and ion-exchange HPLC methods with ultraviolet detection,

This paper was my first as a graduate student of Professor Peter Perlmann at Stockholm University. At the time, RIAs were in full bloom, but they were too sophisticated for many areas of research and diagnosis because they required expensive equipment and used antigens and antibodies labeled with radioactive isotopes with short half-lives. We wanted something simpler with the same sensitivity. Techniques for labeling antibodies with enzymes had been described for immunohistochemistry (1), and we thought they could be useful for serologic assays as well. First, we gave the prospective enzyme immunoassay a name: enzymelinked immunosorbent assay, or ELISA (an important decision). Second, we chose to use an enzyme for which there was, at the time, a soluble and sensitive substrateproduct system, namely alkaline phosphatase. Third, we used the procedure of a standard RIA, i.e., a com

BACKGROUND High-sensitivity cardiac troponin T (hs-cTnT) is a biomarker used in diagnosing myocardial injury. The clinical utility and the variation of this biomarker over time remain unclear in hemodialysis (HD) and peritoneal dialysis (PD) patients. We sought to determine whether hs-cTnT concentrations were predictive of myocardial infarction (MI) and death and to examine hs-cTnT variability over a 1-year period. METHODS A total of 393 nonacute HD and PD patients (70% HD and 30% PD) were followed in a prospective observational study for new MI and death. RESULTS Median hs-cTnT was 57 ng/L (interquartile range, 36–101 ng/L) with no observed difference between HD and PD patients (P = 0.11). Incremental increases in mortality (P = 0.024) and MI (P = 0.001) were observed with increasing hs-cTnT quartiles. MI incidence increased significantly across quartiles in both HD and PD patients (P = 0.012 and P = 0.025, respectively), whereas mortality increased only in HD patients (P = 0.015)....

Total homocysteine is defined as the sum of all homocysteine species in plasma/serum, including free and proteinbound forms. In the present review, we compare and evaluate several techniques forthe determination of total homocystelne. Because these assays include the conversion of all forms into a single species by reduction, the redistribution between free and protein-bound homocysteine through disulfide interchange does not affect the results, and total homocysteine can be measured in stored samples. Total homocysteine in whole blood increases at room temperature because of a continuous production and release of homocysteine from blood cells, but artificial increase is low if the blood sample is centrifuged within 1 h of collection or placed on ice. Different methods correlate well, and values between 5 and 15 mol/L in fasting subjects are considered normal. Total homocysteine in serum/plasma is increased markedly in patients with cobalamin or folate deficiency, and decreases only when they are treated with the deficient vitamin. Total homocysteine is therefore of value for the diagnosis and follow-up of these deficiency states and may compensate for weaknesses of the traditional laboratory tests. In addition, total homocysteine is an independent risk factor for premature cardiovascular diseases. These disorders justify introduction of the total homocysteine assay in the routine clinical chemistry laboratory.

linear with respect to a lysate volume of 0 -300 L (r 2 ϭ 0.997). The influence of the substrate concentration on TPMT activity is shown in , B and C. K m s were 227 and 4.9 mol/L for 6-MP and SAM, respectively, and the maximum velocities (V max ) were 28.1 and 24.9 nmol/h per mL of packed cells. These values are similar to those reported previously using a radiochemical assay . The TPMT activity determined in a population of Caucasian subjects was 10.4 -41.7 nmol/h per mL of packed cells with a mean value of 28.9 nmol/h per mL of packed cells. These preliminary data are in close agreement with the results reported previously in an adult Caucasian European population (9, 13 ). One subject (2.4%) had TPMT in the intermediate range, 40 (97.6%) subjects had high TPMT activity, and no patient had low or undetect-

We describe the preparation of a lyophilized material containing purified human pancreatic a-amylase and the certification of its catalytic concentration. The enzyme was purified from human pancreas by ammonium sulphate precipitation and chromatography successively on DEAE-Sephacel, CM-Sepharose and Sephadex G-75. The purified enzyme Nonstandard abbreviations: IFCC, International Federation had a specific activity of 52.9 kU/g protein and was >99% pure on polyacrylamide gel electrophoresis. Only trace amounts of lipase and lactate dehydrogenase were detected in the purified fraction. The purified pancreatic a-amylase had a molar mass of 57 500 g/mol and an isoelectric point at 7.1. The material was prepared by diluting the purified or-amylase in a matrix containing PIPES buffer 25 mmol/1, pH 7.0, sodium chloride 50 mmol/l, calcium chloride 1.5 mmol/1, EDTA 0.5 mmol/1 and human serum albumin 30 g/l, dispensing in ampoules and freeze-drying. The ampoules were homogeneous and the yearly loss of activity on the basis of accelerated degradation studies was less than 0.01% at -20°C. The certified value for or-amylase catalytic concentration in the reconstituted reference material is 555 U/1 _+ 11 U/I when measured by the specified method at 37°C. The material can be used to verify the comparability of results from different laboratories, for intra-laboratory quality control or for calibration of a-amylase catalytic concentration measurements.

The first generation of troponin T ELISA (TnT 1) can yield false-positive results in patients with severe skeletal muscle injury. Therefore, a cardiac-specific second-generation troponin T ELISA (TnT 2) was developed, in which the cross-reactive antibody 1B10 has been replaced by a high-affinity cardiac-specific antibody M11.7. No cross-reactivity of TnT 2 was observed with purified skeletal muscle troponin T (1000 micrograms/L) or in test samples from 43 marathon runners and 24 patients with rhabdomyolysis and highly increased creatine kinase. TnT 2 was increased > 0.2 microgram/L in 5 of 40 patients with renal failure and in 4 of 20 muscular dystrophy patients. The detection limit is 0.012 microgram/L. Day-to-day imprecision (CV) within the range 0.19-14.89 micrograms/L was < 5.8%. In 4955 patients without myocardial damage, 99.6% had TnT < 0.10 microgram/L. Assay comparison (TnT 1 vs TnT 2) over the whole concentration range (i.e., in 323 samples from AMI-suspected patie...

We presentevidence for the utilityof an improvedassay for the activity of lactate dehydrogenase (EC 1.1.1.27) isoen-zymes1 and 2 in serum, involvinginhibitionof the H-subunit of LD by pyruvate at pH 7.1. Resultscorrelate well with the LD-1/total LD ratio as evaluated by immunologicalassay and, as an indexto infarct, the method is superiorto either the change in CK-MB activityor to the LD-1 activity or to a combinationof these tests, as is the percentage of LD-1 to total LD activity. Moreover, the percentage inhibition ofLD activity by pyruvate may have an advantageover other methods of isoenzyme fractionation because of its smaller populationCV for patients with acute myocardialinfarction than is true of other methods. We also demonstrate how, usinga lineardiscriminantanalysis,we comparedthis method with alternative methods.We determinedthat evaluation of CK-MB isoenzymecontributesno informationin additionto that obtainedfrom the LD-1 isoenzyme.

Colorectal carcinoma is the third most common cancer in the United States. Proper and standardized pathologic staging is vital for prognostic assessment and impacts therapeutic decisions. The Tumor Node Metastasis (TNM) staging system was developed by the American Joint Committee on Cancer (AJCC) to be a data-driven, evidence-based staging system providing an accurate prediction of outcome. The AJCC 7th edition (2010) included several changes clarifying some issues and leading to new controversies. We aim to address selected challenging issues in tumor T staging, neoadjuvant treatment effects in rectal cancer, and definition of lymph node vs tumor deposit. Serosal involvement in colorectal cancer is staged as T4, which is associated with decreased survival and may impact additional therapy decisions. Although careful sampling and sectioning are helpful, challenges remain in interpretation of tumor within 1 mm of serosal surface with a reaction. Elastic stain as a surrogate marker fo...

Metanephrines are O-methylated metabolites of catecholamines. We report the use of liquid chromatography with electrochemical detection to determine plasma concentrations of normetanephrine (NMN) and metanephrine (MN). Plasma NMN and MN in 32 normal volunteers and inpatients were compared with concentrations in 23 patients with pheochromocytoma. Metanephrines were adsorbed from plasma onto a cation-exchange column and eluted with ammoniacal methanol. The dried residue was dissolved in mobile phase and injected onto a reversedphase column. Recoveries of NMN and MN from 1 mL of plasma averaged 50-70%, and resultsvaried linearlywith quantity injected over a range of 0.13-55 pmol. The detection limit was 25 fmol for NMN and 50 fmol for MN. Intra-assay CVs were <5%. In normal volunteers and inpatients, plasma concentrations of NMN ranged between 0.12 and 0.73 nmol/L (mean 0.38 nmol/L), and MN between 0.06 and 0.63 nmol/L (mean 0.19 nmol/L). Plasma NMN concentrations were increased in all 23 patients with pheochromocytoma (range 1-172 nmol/L), whereas MN concentrations (range 0.10-382 nmol/L) were increased in only 9 patients. The assay method is reliable and sensitive and offers an approach to examine the extraneuronal metabolism of catecholamines. The method may also be useful in the diagnosis of pheochromocytoma. AddItional Keyphraaes: chromatography, reversed-phase catecholamine pheochromocytoma Normetanephrine (NMN) and metanephrine (MN), O-methylated metabolites of norepinephrine and epinephrine, are produced by the actions of catechol-Omethyltransferase (EC 2.1.1.6), an enzyme largely confined to extraneuronal tissues (1 )3 Measurements of NMN and MN concentrations in biological fluids may therefore provide a means to examine extraneuronal metabolism of catecholamines. Liquid chromatography and gas chromatography! mass spectrometry methods have been described for Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, and2 Hypertension-Endocrine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda,MD. 'Address for correspondence: Building 10, Room 5N214, National Institutes of Health, Bethesda,MD 20892. 3Nonstandard abbreviations: MN, metanephrune;NMN, normetanephrine; MHPEA, 3-methoxy-4-hydroxyphenylethylamine; HMBA, 4-hydroxy-3-methoxybenzylamine;EHPEA, 3-ethoxy-4hydroxyphenylethanolamine;and FNMN, 6-fluoronormetanephrue.

In this study, we investigated the role of hormones in the pathogenesis of calcifications in ovary and in endometrium and their neoplasms of the gynecologic tract and assessed the anatomic location and incidence of these calcifications. The study consists of three parts designed to investigate the pathogenesis, the location, and the incidence of calcifications in ovary and endometrium and their neoplasms. In the first part, 79 female guinea pigs were divided into 10 groups, and different hormones, given weekly for 12 months, were administered to the guinea pigs by group. A control group of 7 guinea pigs received sterile water. Calcifications developed in 5 of 7 guinea pigs treated with prolactin, 10 of 20 treated with human chorionic gonadotropin, 5 of 11 treated with estradiol, 3 of 7 treated with estrone, 1 of 6 treated with growth hormone, and 1 of 10 treated with testosterone; in 20 of the guinea pigs, the calcifications developed in the stroma of the endometrium, and in 5 guinea pigs, they developed in the ovary. The second part of the study consisted of an evaluation of the specific location of calcifications in 43 consecutive human surgical ovaries and endometria. Calcifications were seen only in the stroma in 100% of the ovarian serous adenofibroma specimens; in ovarian serous borderline neoplasms, the stroma contained 70 to 100% of the calcifications, and the epithelium had 0 to 30% of the calcifications. In ovarian serous carcinoma specimens, the calcifications were seen in the stroma in 50 to 60% of the cases, in the epithelium in 40% of the cases, and in areas of necrosis in 10% of the cases.

The emergence of novel technologies allows researchers to facilitate the comprehensive analyses of genomes, transcriptomes, and proteomes in health and disease. The information that is expected from such technologies may soon exert a dramatic change in the pace of cancer research and impact dramatically on the care of cancer patients. These approaches have already demonstrated the power of molecular medicine in discriminating among disease subtypes that are not recognizable by traditional pathologic criteria and in identifying specific genetic events involved in cancer progression. This review

The advent of in vitro DNA amplification has enabled rapid acquisition of genomic information. We present here an analogous technique for protein detection, in which the coordinated and proximal binding of a target protein by two DNA aptamers promotes ligation of oligonucleotides linked to each aptamer affinity probe . The ligation of two such proximity probes gives rise to an amplifiable DNA sequence that reflects the identity and amount of the target protein. This proximity ligation assay detects zeptomole (40 × 10 -21 mol) amounts of the cytokine platelet-derived growth factor (PDGF) without washes or separations, and the mechanism can be generalized to other forms of protein analysis.

Restless legs syndrome (RLS) is a neurological disorder that may be related to iron misregulation at the level of the central nervous system. Evidence that iron is involved in RLS comes from magnetic resonance imaging data, autopsy studies, analyses of cerebrospinal fluid (CSF), and correlations of symptoms with serum ferritin. To further examine the possibility that brain iron status is insufficient in RLS, we determined ferritin levels in the CSF. Specifically, we differentiated between the H-and L-subunits of ferritin, because these peptides are expressed from different chromosomes and have different functions. We measured H-and L-ferritin subunit levels in control and RLS human CSF using immunoblot analysis and found that both H-and L-ferritin are significantly decreased in early but not late-onset RLS. Additionally, we quantified total protein in each CSF sample to establish that the decrease in ferritin subunits in RLS did not reflect a decrease in total protein in CSF. Furthermore, we used equal amounts of total CSF protein in the immunoblot analyses, in contrast to previously published studies that provided only volumetric data, to determine which approach was more accurate for quantifying the amount of ferritin relative to other proteins in CSF. Our results establish a protein standard in RLS, provide a comparative analysis of protein-controlled versus volumetric immunoblot techniques, and argue for a profound loss of iron storage capacity in the brain in RLS, specifically in the early onset RLS phenotype. These data suggest that CSF ferritin levels may provide a biomarker for assisting in the diagnosis of RLS. (J Lab Clin Med 2006;147:67-73)

BACKGROUND: ⌬ 9-Tetrahydrocannabinol (THC), 11hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH) have been reported in blood from frequent cannabis smokers for an extended time during abstinence. We compared THC, 11-OH-THC, THCCOOH, cannabidiol, cannabinol, THC-glucuronide, and THCCOO-glucuronide blood and plasma disposition in frequent and occasional cannabis smokers. METHODS: Frequent and occasional smokers resided on a closed research unit and smoked one 6.8% THC cannabis cigarette ad libitum. Blood and plasma cannabinoids were quantified on admission (approximately 19 h before), 1 h before, and up to 15 times (0.5-30 h) after smoking. RESULTS: Cannabinoid blood and plasma concentrations were significantly higher in frequent smokers compared with occasional smokers at most time points for THC and 11-OH-THC and at all time points for THCCOOH and THCCOO-glucuronide. Cannabidiol, cannabinol, and THC-glucuronide were not significantly different at any time point. Overall blood and plasma cannabinoid concentrations were significantly higher in frequent smokers for THC, 11-OH-THC, THCCOOH, and THCCOO-glucuronide, with and without accounting for baseline concentrations. For blood THC Ͼ5 g/L, median (range) time of last detection was 3.5 h (1.1-Ͼ30 h) in frequent smokers and 1.0 h (0-2.1 h) in 8 occasional smokers; 2 individuals had no samples with THC Ͼ5 g/L. CONCLUSIONS: Cannabis smoking history plays a major role in cannabinoid detection. These differences may impact clinical and impaired driving drug detection. The presence of cannabidiol, cannabinol, or THCglucuronide indicates recent use, but their absence does not exclude it.

We studied the changes in blood glucose concentration in blood samples collected in heparinized specimen tubes containing no other preservative, or containing NaF, D-mannose, or a combination of NaF and D-mannose. Blood concentration in samples taken into NaF decreased by 0.40 mmol/L in the first 2 h; thereafter, there was no change. In samples collected into mannose there was a small but significant decrease in blood glucose concentration with time. When samples containing mannose were analyzed immediately after collection, the concentration of glucose was higher than in later analyses, probably because of an exchange of intracellular glucose for extracellular mannose. When a combination of NaF and mannose was used, the blood glucose concentration was relatively stable but slightly higher than nonpreserved samples for the next 24 h. However, samples containing mannose were unsuitable for electrolyte analysis. We conclude that a combination of D-mannose and NaF may be a better prese...

relevance of the observed effects. We conclude that the sequential measurement of OC and possibly also of bone ALP during the first 2 months after fracture might be used to predict delayed fracture healing. Previous studies have been very limited, and because of methodologic problems, they are only partly comparable with our study. Further studies are needed.

A series of 25 sera were assayed with the proposed system, in duplicate, each day for five days; the standard deviation of the results was ± 2.5 mg/dl. Correlation results for 33 sera assayed with the proposed system and with an automated o-toluidine one

Derde deelstudie van het project 'Landschappen van armoede' Annelou Ypeij Erik Snel Werkstukken Sociale Vraagstukken en Beleid Armoede en bestaansstratiegieën: Formele en informele sociale zekerheid in Amsterdam-Zuidoost: derde deelstudie van project 'Landschappen van armoede' / Annelou Ypeij & Erik Snel. Trefw.: Armoede -Beleving van armoede -Bestaansstrategieën -Sociale ondersteuning -sociale zekerheid. Rotterdam: RISBO Contractresearch BV / Erasmus Universiteit Rotterdam. Januari 2002 Verkoopprijs: € 15,90 (inclusief BTW en administratiekosten en exclusief verzendkosten) Exemplaren van deze uitgave zijn te bestellen bij: Secretariaat RISBO Erasmus Universiteit Rotterdam Postbus 1738 3000 DR Rotterdam tel: 010-4082124 fax: 010-4529734 © Copyright RISBO Contractresearch BV. Alle rechten voorbehouden. Niets uit deze uitgave mag worden vermenigvuldigd en/of openbaar gemaakt door middel van druk, fotokopie, microfilm of op welke wijze dan ook zonder voorafgaande toestemming van de Directie van het Instituut. ISBN 9076613-17-6 i Inhoudsopgave Andere gepubliceerde deelstudies: Ypeij, Annelou, Erik Snel en Godfried Engbersen (1999) Armoede in Amsterdam-Noord. Eerste deelstudie van project Landschappen van armoede, Rotterdam: Risbo Contract Research en Staring, Richard, Godfried Engbersen en Annelou Ypeij (2001) Armoede, migranten en informaliteit in Rotterdam-Delfshaven. Tweede Deelstudie van project Landschappen van armoede Rotterdam: Risbo Contract Research.

Cancer biomarkers are commonly used in pediatrics to monitor cancer progression, recurrence, and prognosis, but pediatric reference value distributions have not been well established for these markers. The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) sought to develop a pediatric database of covariate-stratified reference value distributions for 11 key circulating tumor markers, including those used in assessment of patients with childhood or adult cancers. Healthy community children from birth to 18 years of age were recruited to participate in the CALIPER project with informed parental consent. We analyzed serum samples from 400-700 children (depending on the analyte in question) on the Abbott Architect ci4100 and established reference intervals for α-fetoprotein (AFP), antithyroglobulin (anti-Tg), human epididymis protein 4 (HE4), cancer antigen 125 (CA125), CA15-3, CA19-9, progastrin-releasing peptide (proGRP), carcinoembryonic antigen (CEA), squamou...

The ABCA1 gene encodes for a member of subfamily A of the ATP-binding cassette transporters that plays an important role in cellular export of cholesterol and phospholipids; therefore, quantification of the ABCA1 mRNA is critical in many studies related to its expression and regulation by metabolic factors, nutritional status, and new antiatherogenic drug candidates. We developed a rapid, sensitive, specific, and reproducible real-time reverse transcription-PCR (RT-PCR) method for detection and quantification of ABCA1 transcripts in total RNA isolated from cultured human cells and tissues. To quantify ABCA1 mRNA, we generated a calibration curve from serial dilutions of in vitro-transcribed RNA corresponding to an amplified ABCA1 cDNA 205-bp fragment (homologous calibrator). Two pairs of fluorescent hybridization probes were used to detect the ABCA1 and porphobilinogen deaminase (PBGD) mRNAs; the latter served as an internal control. PCR was performed as real-time amplification of A...

Multi-proxy approach was used to reconstruct the environmental conditions of remote lakes in the High Tatra Mountains (Slovakia) over the past few centuries (approximately 500-1000 years). Short sediment cores (*30 cm) taken from three morphologically similar glacial lakes distributed along altitudinal gradient (subalpine to alpine conditions) were analysed for organic matter content (LOI), diatoms and chironomids. Both descriptive and correlative approaches were used for analysing stratigraphical data. Predictive canonical correspondence analysis and co-correspondence analysis were applied to directly relate physical and biological proxies to each other. The relationship between LOI and biotic proxies was inconsistent across groups and lakes. Concordant patterns in diatom and chironomid composition were found in two non-acidified lakes. Common trends in those assemblages indicated major past environmental events such as the Little Ice Age, air pollution and lake acidification. In contrast, no relationship between the composition of diatom and chironomid assemblages was found in the formerly acidified lake, suggesting different responses of assemblages to acidification. While chironomids showed shifts that are attributable to recovery, diatoms assemblage remained relatively stable throughout the uppermost layers of the sediment record. On the other hand, climatic-driven changes in assemblages detected in the deeper layers were more pronounced in diatoms than in chironomids.

BACKGROUND In cancer patients, circulating cell-free DNA (ccfDNA) can contain tumor-derived DNA (ctDNA), which enables noninvasive diagnosis, real-time monitoring, and treatment susceptibility testing. However, ctDNA fractions are highly variable, which challenges downstream applications. Therefore, established preanalytical work flows in combination with cost-efficient and reproducible reference materials for ccfDNA analyses are crucial for analytical validity and subsequently for clinical decision-making. METHODS We describe the efforts of the Innovative Medicines Initiative consortium CANCER-ID (http://www.cancer-id.eu) for comparing different technologies for ccfDNA purification, quantification, and characterization in a multicenter setting. To this end, in-house generated mononucleosomal DNA (mnDNA) from lung cancer cell lines carrying known TP53 mutations was spiked in pools of plasma from healthy donors generated from 2 different blood collection tubes (BCTs). ccfDNA extracti...

No reliable estimate of the prevalence of doping in elite sports has been published. Since 2001, the international governing body for athletics has implemented a blood-testing program to detect altered hematological profiles in the world's toplevel athletes.

We examine the effect of systematic bias and random error, quality control, and intraperson biological varia- tion on the National Cholesterol Education Program (NCEP) clinical classifications for reported lipid mea- surements. We consider misclassification to occur if a true lipid homeostatic set point is within a desirable range but the reported lipid value is in a high-risk range, or if

Background: Saliva is an alternative biologic matrix for drugs-of-abuse testing that offers the advantages of noninvasive, rapid, and easy sampling. We studied the excretion profile of 3,4-methylenedioxymethamphet- amine (MDMA) and its metabolites in both saliva and plasma, as well the effect of the drug on salivary pH. Methods: Saliva and plasma samples were obtained from eight healthy MDMA consumers after