Response to: Reliability and validity of telomere length measurements.
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ABSTRACT:
SUBMITTER: Verhulst S
PROVIDER: S-EPMC6068938 | biostudies-literature | 2016 Aug
REPOSITORIES: biostudies-literature
Publications
Response to: Reliability and validity of telomere length measurements.
Verhulst Simon S Susser Ezra E Factor-Litvak Pam R PR Simons Mirre M Benetos Athanase A Steenstrup Troels T Kark Jeremy D JD Aviv Abraham A
International journal of epidemiology 20160801 4
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Project description:PurposeVarious strategies for improving reliability of fascicle identification on ultrasound images are used in practice, yet these strategies are untested for effectiveness. Studies suggest that the largest part of differences between fascicle lengths on one image are attributed to the error on the initial image. In this study, we compared reliability results between different strategies.MethodsStatic single-image recordings and image sequence recordings during passive ankle rotations of the medial gastrocnemius were collected. Images were tracked by three different raters. We compared results from uninformed fascicle identification (UFI) and results with information from dynamic length changes, or data-informed tracking (DIT). A second test compared tracking of image sequences of either fascicle shortening (initial-long condition) or fascicle lengthening (initial-short condition).ResultsIntra-class correlations (ICC) were higher for the DIT compared to the UFI, yet yielded similar standard error of measurement (SEM) values. Between the initial-long and initial-short conditions, similar ICC values, coefficients of multiple determination, mean squared errors, offset-corrected mean squared errors and fascicle length change values were found for the DIT, yet with higher SEM values and greater absolute fascicle length differences between raters on the first image in the initial-long condition and on the final image in the initial-short condition.ConclusionsDIT improves reliability of fascicle length measurements, without lower SEM values. Fascicle length on the initial image has no effect on subsequent tracking results. Fascicles on ultrasound images should be identified by a single rater and care should be taken when comparing absolute fascicle lengths between studies.
| S-EPMC5733898 | biostudies-literature
Project description:Pectoralis minor muscle length is believed to play an important role in shoulder pain and dysfunction. Current clinical procedures for assessing pectoralis minor muscle length may not provide the most useful information for clinical decision making.To establish the reliability and construct validity of a novel technique to measure pectoralis minor muscle length under actively and passively lengthened conditions.Cross-sectional repeated measures.Thirty-four healthy adults (age: 23.9, SD=1.6 years; 18 females) participated in this study. Pectoralis minor muscle length was measured on the dominant arm in three length conditions: resting, actively lengthened, and passively lengthened. Based upon availability, two raters, out of a pool of five, used a caliper to measure the distance between the coracoid process and the 4th rib. The average of two pectoralis minor muscle length measures was used for all muscle length conditions and analyses. Intraclass correlation coefficients determined intra-and inter-rater reliability, and measurement error was determined via standard error of measurement and minimal detectable change. Construct validity was assessed by ANOVA to determine differences in muscle length across the three conditions.Our intra- and inter-rater reliability values across all three conditions ranged from 0.84 to 0.92 and from 0.80 to 0.90, respectively. Significant differences (p<0.001) in muscle length were found among all three conditions: rest-active (3.66; SD=1.36cm), rest-passive (4.72, SD=1.41cm), and active-passive (1.06, SD=0.47cm).The techniques described in this study for measuring pectoralis minor muscle length under resting and actively and passively lengthened conditions have acceptable reliability for clinical decision making.
| S-EPMC5537459 | biostudies-other
Project description:BackgroundThe femoral canal is frequently measured preoperatively in cases where an intramedullary device is planned for operative fixation of a fracture. To our knowledge, a formal assessment of validity and reliability of preoperative canal measurements has not been previously performed.Questions/purposesThis study aims to determine the validity and reliability of preoperative canal measurements of the femur made on plain radiographs using comparison with curved planar reformation software as the gold standard.MethodsFifty-six patients were identified based on availability of anterior-posterior (AP) and lateral radiographs of the femur and computed tomography (CT) of the lower extremity. Four "raters" measured the canal diameter at its narrowest point and the distance from the lesser trochanter to the isthmus on the AP, lateral radiograph, and CT. The width of the femoral nail on AP radiographs was also measured to determine magnification error. Curved planar reformation (CPR) was used to provide the most accurate calculation of the canal diameter.ResultsCompared to the isthmus position determined by CPR, the measurement was most accurate on an AP and the diameter of the canal was most accurate using coronal CT, followed by AP radiographs. The measured canal diameter of the fractured femur on APs was compared to that of the used implant and varied by 1 mm.Discussion/conclusionThe AP plain radiographic measurement was found to be more accurate for determination of the canal diameter compared to the lateral radiograph. These findings confirm the utility of preoperative canal measurements in predicting the feasibility of placing a specific size intramedullary implant.
| S-EPMC3757481 | biostudies-literature
Project description:In humans, DNA methylation (DNAm) based estimators of telomere length (TL) have been shown to better predict TL-associated variables (e.g., age, sex, and mortality) than TL itself. The biological significance of DNAm-based estimators of TL (DNAmTL) is unclear. In vitro DNAmTL shortens with cell replications, even when telomerase is maintaining TL. Telomerase is typically suppressed in humans, except in testes. Accordingly, sperm TL increases with age, and offspring with greater paternal age at conception (PAC) have longer TL. Thus, we expect that PAC associations with DNAmTL can shed light on whether in vivo cell replications in the presence of high telomerase activity (production of sperm) shorten DNAmTL or if PAC-lengthened TL causes lengthened DNAmTL. In a pre-registered analysis, using data from 1733 blood samples from the Philippines, we examined the association between paternal age at conception (PAC) and offspring DNAmTL. We did not find an association between PAC and DNAmTL but found a positive association of paternal grandfather's age at father's conception predicting grandchild's DNAmTL. In post hoc analyses, we examined how DNAmTL versus qPCR-measured TL (qPCR-TL) correlated with measures typically associated with TL. Contrary to previous findings, on almost all measures of external validity (correlations with parental TLs, southern blot TL, and age), qPCR-TL outperformed DNAmTL. The "kilobase" units of DNAm-based estimators of TL showed considerable deviations from southern blot-derived kilobase measures. Our findings suggest that DNAmTL is not a reliable index of inherited aspects of TL and underscores uncertainty about the biological meaning of DNAmTL.
| S-EPMC11226585 | biostudies-literature
Project description:Technical challenges associated with telomere length (TL) measurements have prompted concerns regarding their utility as a biomarker of aging. Several factors influence TL assessment via qPCR, the most common measurement method in epidemiological studies, including storage conditions and DNA extraction method. Here, we tested the impact of power supply during the qPCR assay. Momentary fluctuations in power can affect the functioning of high-performance electronics, including real-time thermocyclers. We investigated if mitigating these fluctuations by using an uninterruptible power supply (UPS) influenced TL assessment via qPCR. Samples run with a UPS had significantly lower standard deviation (p < 0.001) and coefficient of variation (p < 0.001) across technical replicates than those run without a UPS. UPS usage also improved exponential amplification efficiency at the replicate, sample, and plate levels. Together these improvements translated to increased performance across metrics of external validity including correlation with age, within-person correlation across tissues, and correlation between parents and offspring.
| S-EPMC7954403 | biostudies-literature
Project description:How many times does a typical hematopoietic stem cell (HSC) divide to maintain a daily production of over 1011 blood cells over a human lifetime? It has been predicted that relatively few, slowly dividing HSCs occupy the top of the hematopoietic hierarchy. However, tracking HSCs directly is extremely challenging due to their rarity. Here, we utilize previously published data documenting the loss of telomeric DNA repeats in granulocytes, to draw inferences about HSC division rates, the timing of major changes in those rates, as well as lifetime division totals. Our method uses segmented regression to identify the best candidate representations of the telomere length data. Our method predicts that, on average, an HSC divides 56 times over an 85-year lifespan (with lower and upper bounds of 36 and 120, respectively), with half of these divisions during the first 24 years of life.
| S-EPMC10285640 | biostudies-literature
Project description:The cervical range of motion device (CROM) has been shown to provide reliable forward head position (FHP) measurement when the upper cervical angle (UCA) is controlled. However, measurement without UCA standardization is reflective of habitual patterns. Criterion validity has not been reported. The purposes of this study were to establish: (1) criterion validity of CROM FHP and UCA compared to Optotrak data, (2) relative reliability and minimal detectable change (MDC95) in patients with and without cervical pain, and (3) to compare UCA and FHP in patients with and without pain in habitual postures.(1) Within-subjects single session concurrent criterion validity design. Simultaneous CROM and OP measurement was conducted in habitual sitting posture in 16 healthy young adults. (2) Reliability and MDC95 of UCA and FHP were calculated from three trials. (3) Values for adults over 35 years with cervical pain and age-matched healthy controls were compared.(1) Forward head position distances were moderately correlated and UCA angles were highly correlated. The mean (standard deviation) differences can be expected to vary between 1·48 cm (1·74) for FHP and -1·7 (2·46)° for UCA. (2) Reliability for CROM FHP measurements were good to excellent (no pain) and moderate (pain). Cervical range of motion FHP MDC95 was moderately low (no pain), and moderate (pain). Reliability for CROM UCA measurements was excellent and MDC95 low for both groups. There was no difference in FHP distances between the pain and no pain groups, UCA was significantly more extended in the pain group (P<0·05).Cervical range of motion FHP measurements were only moderately correlated with Optotrak data, and limits of agreement (LOA) and MDC95 were relatively large. There was also no difference in CROM FHP distance between older symptomatic and asymptomatic individuals. Cervical range of motion FHP measurement is therefore not recommended as a clinical outcome measure. Cervical range of motion UCA measurements showed good criterion validity, excellent test-retest reliability, and achievable MDC95 in asymptomatic and symptomatic participants. Differences of more than 6° are required to exceed error. Cervical range of motion UCA shows promise as a useful reliable and valid measurement, particularly as patients with cervical pain exhibited significantly more extended angles.
| S-EPMC4727731 | biostudies-literature
Project description:BackgroundTelomere length (TL) is considered a biological marker of aging and may indicate age-related disease susceptibility. Adults and children show a fixed ranking and tracking of TL over time. However, the contribution of an individual's initial birth TL to their later life TL is unknown. We evaluated change and tracking of TL from birth to child- and adulthood.MethodsTelomere length at birth was measured using qPCR in two independent prospective birth cohorts. After a median follow-up period of 4 years in ENVIRONAGE (n = 273) we assessed leukocyte telomere length (LTL) and after 23 years in EFPTS (n = 164) buccal TL was assessed. Correlations and multivariable regression models were applied to study telomere tracking and determinants of TL change from birth onwards.FindingsIn children, LTL at the age of 4 correlates with TL at the start of life both in cord blood (r = 0.71, P < 0.0001;) and placenta (r = 0.60, P < 0.0001) and was -11.2% and -33.1% shorter, respectively. In adulthood, buccal TL at the age of 23 correlates with placental TL (r = 0.46, P < 0.0001) and was -35.9% shorter. TL attrition was higher in individuals with longer birth TL. However, based on TL ranking, individuals do not tend to change dramatically from TL rank after 4 or 23 years of follow-up. Finally, longer maternal TL associates with lower telomere attrition in the next generation.InterpretationThe high prediction of newborn TL for later life TL, and stable TL ranking from birth onwards underscores the importance of understanding the initial setting of newborn TL and its significance for later life.FundingEuropean Research Council (ERC-StG310898) and Flemish Scientific Fund (12X9620N).
| S-EPMC7808927 | biostudies-literature
Project description:BackgroundAttention bias to threat is a fundamental transdiagnostic component and potential vulnerability factor for internalizing psychopathologies. However, the measurement of attentional bias, such as traditional scores from the dot-probe paradigm, evidence poor reliability and do not measure intra-individual variation in attentional bias.MethodsThe present study examined, in three independent samples, the psychometric properties of a novel attentional bias (AB) scoring method of the dot-probe task based on responses to individual trials. For six AB scores derived using the response-based approach, we assessed the internal consistency, test-retest reliability, familial associations, and external validity (using Social Anxiety Disorder, a disorder strongly associated with attentional bias to threatening faces).ResultsCompared to traditional AB scores, response-based scores had generally better internal consistency (range of Cronbach's alphas: 0.68-0.92 vs. 0.41-0.71), higher test-retest reliabilities (range of Pearson's correlations: 0.26-0.77 vs. -0.05-0.35), and were more strongly related in family members (range of ICCs: 0.11-0.27 vs. 0-0.05). Furthermore, three response-based scores added incremental validity beyond traditional scores and gender in the external validators of current and lifetime Social Anxiety Disorder.ConclusionsFindings indicate that response-based AB scores from the dot-probe task have better psychometric properties than traditional scores.
| S-EPMC8939897 | biostudies-literature
Project description:The number of (TTAGGG)n repeats at the ends of chromosomes is highly variable between individual chromosomes, between different cells and between species. Progressive loss of telomere repeats limits the proliferation of pre-malignant human cells but also contributes to aging by inducing apoptosis and senescence in normal cells. Despite enormous progress in understanding distinct pathways that result in loss and gain of telomeric DNA in different cell types, many questions remain. Further studies are needed to delineate the role of damage to telomeric DNA, replication errors, chromatin structure, liquid-liquid phase transition, telomeric transcripts (TERRA) and secondary DNA structures such as guanine quadruplex structures, R-loops and T-loops in inducing gains and losses of telomere repeats in different cell types. Limitations of current telomere length measurements techniques and differences in telomere biology between species and different cell types complicate generalizations about the role of telomeres in aging and cancer. Here some of the factors regulating the telomere length in embryonic and adult cells in mammals are discussed from a mechanistic and evolutionary perspective.
| S-EPMC9289283 | biostudies-literature