Developing a DNA methylation assay for human age prediction in blood and bloodstain

Age prediction of an individual based on biological traces remained in a crime scene is of ultimate importance for criminal investigation. Growing evidence indicates that some CpG sites may have age-related methylation changes and thus may be a promising tool for age prediction. In this study, we utilized the pyrosequencing approach to screen age-related CpG (AR-CpG) sites for age prediction. Five AR-CpGs were identified as age-related markers from thirty-eight candidates, among which three CpG sites, ITGA2B_1, NPTX2_3, and NPTX2_4 were never reported in previous studies. We fit a linear regression model for age prediction based on methylation assay for 89 blood samples from donors aged 9–75 years old. The model included four AR-CpG markers in three gene fragments ASPA, ITGA2B and NPTX2 and enabled the age prediction with R² = 0.819. The mean absolute deviation (MAD) from chronological age of the model was 7.870. We validated the linear regression model with a validation set of 40 blood samples, and the prediction MAD was 7.986. There was no statistically significant difference in age prediction between 20 pairs of blood samples and bloodstains. Six pairs of fresh and old bloodstains were analyzed using our assay. The obtained results showed the assay still performed an effective prediction on bloodstains after four-month storage in room conditions. This study indicates that our DNA methylation assay is a reliable and effective method for age prediction for forensic purposes.     

Development of a forensically useful age prediction method based on DNA methylation analysis

Forensic DNA phenotyping needs to be supplemented with age prediction to become a relevant source of information on human appearance. Recent progress in analysis of the human methylome has enabled selection of multiple candidate loci showing linear correlation with chronological age. Practical application in forensic science depends on successful validation of these potential age predictors. In this study, eight DNA methylation candidate loci were analysed using convenient and reliable pyrosequencing technology. A total number of 41 CpG sites was investigated in 420 samples collected from men and women aged from 2 to 75 years. The study confirmed correlation of all the investigated markers with human age. The five most significantly correlated CpG sites in ELOVL2 on 6p24.2, C1orf132 on 1q32.2, TRIM59 on 3q25.33, KLF14 on 7q32.3 and FHL2 on 2q12.2 were chosen to build a prediction model. This restriction allowed the technical analysis to be simplified without lowering the prediction accuracy significantly. Model parameters for a discovery set of 300 samples were R² = 0.94 and the standard error of the estimate = 4.5 years. An independent set of 120 samples was used to test the model performance. Mean absolute deviation for this testing set was 3.9 years. The number of correct predictions ±5 years achieved a very high level of 86.7% in the age category 2–19 and gradually decreased to 50% in the age category 60–75. The prediction model was deterministic for individuals belonging to these two extreme age categories. The developed method was implemented in a freely available online age prediction calculator.     

DNA methylation-based age prediction from saliva: High age predictability by combination of 7 CpG markers

DNA methylation is currently one of the most promising age-predictive biomarkers. Many studies have reported DNA methylation-based age predictive models, but most of these are based on DNA methylation patterns from blood. Only a few studies have examined age-predictive DNA patterns in saliva, which is one of the most frequently-encountered body fluids at crime scenes. In this study, we generated genome-wide DNA methylation profiles of saliva from 54 individuals and identified CpG markers that showed a high correlation between methylation and age. Because the age-associated marker candidates from saliva differed from those of blood, we investigated DNA methylation patterns of 6 age-associated CpG marker candidates (cg00481951, cg19671120, cg14361627, cg08928145, cg12757011, and cg07547549 of the SST, CNGA3, KLF14, TSSK6, TBR1, and SLC12A5 genes, respectively) in addition to a cell type-specific CpG marker (cg18384097 of the PTPN7 gene) in an independent set of saliva samples obtained from 226 individuals aged 18 to 65 years. Multiplex methylation SNaPshot reactions were used to generate the data. We then generated a linear regression model with age information and the methylation profile from the 113 training samples. The model exhibited a 94.5% correlation between predicted and chronological age with a mean absolute deviation (MAD) from chronological age of 3.13 years. In subsequent validation using 113 test samples, we also observed a high correlation between predicted and chronological age (Spearman’s rho = 0.952, MAD from chronological age = 3.15 years). The model composed of 7 selected CpG sites enabled age prediction in saliva with high accuracy, which will be useful in saliva analysis for investigative leads.     

Human age estimation from blood using mRNA,DNA methylation,DNA rearrangement,and telomere length

Establishing the age of unknown persons, or persons with unknown age, can provide important leads in police investigations, disaster victim identification, fraud cases, and in other legal affairs. Previous methods mostly relied on morphological features available from teeth or skeletal parts. The development of molecular methods for age estimation allowing to use human specimens that possess no morphological age information, such as bloodstains, is extremely valuable as this type of samples is commonly found at crime scenes. Recently, we introduced a DNA-based approach for human age estimation from blood based on the quantification of T-cell specific DNA rearrangements (sjTRECs), which achieves accurate assignment of blood DNA samples to one of four 20-year-interval age categories. Aiming at improving the accuracy of molecular age estimation from blood, we investigated different types of biomarkers. We started out by systematic genome-wide surveys for new age-informative mRNA and DNA methylation markers in blood from the same young and old individuals using microarray technologies. The obtained candidate markers were validated in independent samples covering a wide age range using alternative technologies together with previously proposed DNA methylation, sjTREC, and telomere length markers. Cross-validated multiple regression analysis was applied for estimating and validating the age predictive power of various sets of biomarkers within and across different marker types. We found that DNA methylation markers outperformed mRNA, sjTREC, and telomere length in age predictive power. The best performing model included 8 DNA methylation markers derived from 3 CpG islands reaching a high level of accuracy (cross-validated R² = 0.88, SE ± 6.97 years, mean absolute deviation 5.07 years). However, our data also suggest that mRNA markers can provide independent age information: a model using a combined set of 5 DNA methylation markers and one mRNA marker could provide similarly high accuracy (cross-validated R² = 0.86, SE ± 7.62 years, mean absolute deviation 4.60 years). Overall, our study provides new and confirms previously suggested molecular biomarkers for age estimation from blood. Moreover, our comparative study design revealed that DNA methylation markers are superior for this purpose over other types of molecular biomarkers tested. While the new and some previous findings are highly promising, before molecular age estimation can eventually meet forensic practice, the proposed biomarkers should be tested further in larger sets of blood samples from both healthy and unhealthy individuals, and markers and genotyping methods shall be validated to meet forensic standards.     

Epigenome-wide screening of CpG markers to develop a multiplex methylation SNaPshot assay for age prediction

Age prediction can provide important information about the contributors of biological evidence left at crime scenes. DNA methylation has been regarded as the most promising age-predictive biomarker. Measuring the methylation level at the genome-wide scale is an important step to screen specific markers for forensic age prediction. In present study, we screened out five age-related CpG sites from the public EPIC BeadChip data and evaluated them in a training set (115 blood) by multiplex methylation SNaPshot assay. Through full subset regression, the five markers were narrowed down to three, namely cg10501210 (C1orf132), cg16867657 (ELOVL2), and cg13108341 (DNAH9), of which the last one was a newly discovered age-related CpG site. An age prediction model was built based on these three markers, explaining 86.8% of the variation of age with a mean absolute deviation (MAD) of 4.038 years. Then, the multiplex methylation SNaPshot assay was adjusted according to the age prediction model. Considering that bloodstains are one of the most common biological samples in practical cases, three validation sets composed of 30 blood, 30 fresh bloodstains and 30 aged bloodstains were used for evaluation of the age prediction model. The MAD of each set was estimated as 4.734, 4.490, and 5.431 years, respectively, suggesting that our age prediction model was applicable for age prediction for blood and bloodstains in Chinese Han population of 11–71 age. In general, this study describes a workflow of screening CpG markers from public chip data and presents a 3-CpG markers model for forensic age prediction.     

Forensic age prediction for dead or living samples by use of methylation-sensitive high resolution melting

Age prediction with epigenetic information is now edging closer to practical use in forensic community. Many age-related CpG (AR-CpG) sites have proven useful in predicting age in pyrosequencing or DNA chip analyses. In this study, a wide range methylation status in the ELOVL2 and FHL2 promoter regions were detected with methylation-sensitive high resolution melting (MS-HRM) in a labor-, time-, and cost-effective manner. Non-linear-distributions of methylation status and chronological age were newly fitted to the logistic curve. Notably, these distributions were revealed to be similar in 22 living blood samples and 52 dead blood samples. Therefore, the difference of methylation status between living and dead samples suggested to be ignorable by MS-HRM. Additionally, the information from ELOVL2 and FHL2 were integrated into a logistic curve fitting model to develop a final predictive model through the multivariate linear regression of logit-linked methylation rates and chronological age with adjusted R² = 0.83. Mean absolute deviation (MAD) was 7.44 for 74 training set and 7.71 for 30 additional independent test set, indicating that the final predicting model is accurate. This suggests that our MS-HRM-based method has great potential in predicting actual forensic age.     

Energy cost of walking in children with spastic cerebral palsy: Relationship with age,body composition and mobility capacity

The energy cost (EC) of walking is different for typically developing (TD) and children with cerebral palsy (CP). The associated factors of EC are not fully understood in children with CP. We assessed the relationship between EC and age, body surface area (BSA), and gross motor function measure (GMFM). We retrospectively examined data collected between 2003 and 2011 on 276 children aged 4–18 years who were classified as Gross Motor Function Classification System level I, n = 79; II, n = 123; and III, n = 74. Energy cost was assessed while children walked 6–8 min at a comfortable, self-selected speed using their typical walking aids and/or orthoses as part of a clinical gait analysis. During the test, participants wore a breath-by-breath portable gas analysis system, measuring oxygen consumption. To calculate EC (J/kg/m), oxygen consumption was converted to J/kg/min and divided by walking speed. Data were analyzed using linear regression model. Energy cost correlated inversely with age (β = −0.16, R² = 0.02, P = 0.01), BSA (β = −3.35, R² = 0.11, P < 0.0001), and GMFM (β = −0.12, R² = 0.42, P < 0.0001). In the multiple linear regression model, GMFM was the most potent correlate of EC, BSA explained another 10% of the variance (R² = 0.53), and age was a marginally significant correlate of EC (P = 0.08). In summary, in children with CP in our study, EC decreased as GMFM and BSA increased, and GMFM was the most potent correlate of EC.     

Development of a methylation marker set for forensic age estimation using analysis of public methylation data and the Agena Bioscience EpiTYPER system

Individual age estimation has the potential to provide key information that could enhance and extend DNA intelligence tools. Following predictive tests for externally visible characteristics developed in recent years, prediction of age could guide police investigations and improve the assessment of age-related phenotype expression patterns such as hair colour changes and early onset of male pattern baldness. DNA methylation at CpG positions has emerged as the most promising DNA tests to ascertain the individual age of the donor of a biological contact trace. Although different methodologies are available to detect DNA methylation, EpiTYPER technology (Agena Bioscience, formerly Sequenom) provides useful characteristics that can be applied as a discovery tool in localized regions of the genome. In our study, a total of twenty-two candidate genomic regions, selected from the assessment of publically available data from the Illumina HumanMethylation 450 BeadChip, had a total of 177 CpG sites with informative methylation patterns that were subsequently investigated in detail. From the methylation analyses made, a novel age prediction model based on a multivariate quantile regression analysis was built using the seven highest age-correlated loci of ELOVL2, ASPA, PDE4C, FHL2, CCDC102B, C1orf132 and chr16:85395429. The detected methylation levels in these loci provide a median absolute age prediction error of ±3.07 years and a percentage of prediction error relative to the age of 6.3%. We report the predictive performance of the developed model using cross validation of a carefully age-graded training set of 725 European individuals and a test set of 52 monozygotic twin pairs. The multivariate quantile regression age predictor, using the CpG sites selected in this study, has been placed in the open-access Snipper forensic classification website.     

Walking cadence affects rate of plantar foot temperature change but not final temperature in younger and older adults

This study examined the relationship between (1) foot temperature in healthy individuals and walking cadence, (2) temperature change at different locations of the foot, and (3) temperature change and its relationship with vertical pressures exerted on the foot. Eighteen healthy adult volunteers (10 between 30 and 40 years – Age: 33.4 ± 2.4 years; 8 above 40 years – Age: 54.1 ± 7.7 years) were recruited. A custom-made insole with temperature sensors was placed directly onto the plantar surface of the foot and held in position using a sock. The foot was placed on a pressure sensor and the whole system placed in a canvas shoe. Participants visited the lab on three separate occasions when foot temperature and pressure data were recorded during walking on a treadmill at one of three cadences (80, 100, 120 steps/min). The plantar foot temperature increased during walking in both age groups 30–40 years: 4.62 ± 2.00 °C, >40 years: 5.49 ± 2.30 °C, with the rise inversely proportional to initial foot temperature (30–40 years: R² = −0.669, >40 years: R² = −0.816). Foot temperature changes were not different between the two age groups or the different foot locations and did not depend on vertical pressures. Walking cadence affected the rate of change of plantar foot temperature but not the final measured value and no association between temperature change and vertical pressure was found. These results provide baseline values for comparing foot temperature changes in pathological conditions which could inform understanding of pathophysiology and support development of evidence based healthcare guidelines for managing conditions such as diabetic foot ulceration (DFU).     

The arm posture in children with unilateral Cerebral Palsy is mainly related to antero-posterior gait instability

In this observational case-control study we aimed to determine whether altered arm postures in children with unilateral CP (uniCP) are related to gait instability in a specific direction.Antero-posterior and medio-lateral Foot Placement Estimator instability measures and arm posture measures (vertical and antero-posterior hand position, sagittal and frontal upper arm elevation angle) were determined in eleven uniCP (7 years–10 months) and twenty-four typically developing children (9 years–6 months) at two walking speeds. Spearman-rank correlation analyses were made to examine the relationship between antero-posterior and medio-lateral arm posture and gait instability.Arm posture in both planes was related to antero-posterior instability (e.g. sagittal and frontal upper arm elevation angle correlated moderately with antero-posterior instability; R = 0.41, p < 0.001, R = −0.47, p < 0.001). In uniCP, increased antero-posterior instability was associated with a higher (R = −0.62, p = 0.002) and more frontal position of the hemiplegic hand (R = −0.58, p = 0.005), while the non-hemiplegic upper arm was rotated more backward (R = 0.63, p = 0.002) and both upper arms rotated more sideways (hemiplegic: R = −0.58, p = 0.004; non-hemiplegic: R = −0.55, p = 0.008).The altered non-hemiplegic (sagittal and frontal) arm posture in uniCP may be a compensation to reduce antero-posterior gait instability.     

Sex determination from carpal bone volumes: A Multi Detector Computed Tomography (MDCT) study in a Malaysian population

PurposeThe use of Multi Detector Computed Tomography (MDCT) volume measurements of bones for sex determination allows fragile, fragmented human remains to be assessed without compromising the specimen. We set out to assess the ability of MDCT carpal bone volume measurement in determining sex in a Malaysian population.Materials and methods52 healthy volunteers were scanned in a 16-slice MDCT, and the volume of 104 sets of carpal bones was measured using a Syngo workstation (Both CT and workstation-Siemens Healthcare, Erlangen, Germany).ResultsMale carpal bones were of higher volume compared to the female carpal bones (p < 0.001). Area under the curve (AUC) assessment of responder-operator characteristics curves showed that the trapezium bone was best able to predict sex with an AUC of 0.986. At a trapezium bone volume of ⩾1.94 cm³, there was a 93.5% probability that the subject was male. Binary logistic regression analysis found that the highest accuracy was derived using the pisiform, trapezium and capitate bones. There was a strong relationship between sex prediction and grouping of the carpal bone volumes (Nagelkerke R² = 0.923) with an overall prediction accuracy of 97%.ConclusionAll 8 carpal bones exhibit sexual dimorphism to varying degrees. A binary regression analysis combining the 5 carpal bones with the highest predictive values for sex produces an accurate predictive model.     

A new method to reduce false positive results in breast MRI by evaluation of multiple spectral regions in proton MR-spectroscopy

ObjectivesTo investigate whether the evaluation of multiple spectral regions can increase the diagnostic performance of ¹H-MRS of the breast and reduce false positive findings.Methods93 patients (mean age 56 years, range 23–79) undergoing breast MRI for routine clinical indications on a 1.5 T scanner were eligible for this IRB-approved prospective study. Suspicious enhancing lesions ≥8 mm underwent single-voxel point-resolved ¹H-MRS (PRESS, TR = 2000 ms, TE = 272 ms). Histology showed 69 malignant and 24 benign lesions. The Signal-to-Noise ratio of choline, olefinic acids and the water-to-methylene ratio were measured. The area under the ROC-curve (AUC) was used to evaluate single measurements. Combined diagnostic accuracy was explored using a 10-fold cross-validated Chi-squared automatic interaction detection (CHAID) analysis. Inter-reader agreement was evaluated in a subset of patients.ResultsA significant AUC for differentiation between benign and malignant lesions was identified for choline (0.733, P = 0.001), olefinic acids (0.769, P = 0.0001) and water-to-methylene ratio (0.704, P = 0.003). All three variables were included in a classification algorithm using CHAID methodology. Using this classification, 70.8% (17/24) false positive diagnoses in benign lesions would have been avoided. Inter-reader agreement was almost perfect.ConclusionsThe combined evaluation of multiple spectral regions can increase the diagnostic performance of ¹H-MRS and potentially reduce false positive findings.     

Heart rate and blood lactate responses during Taekwondo training and competition

ObjectiveThe study investigated physical fitness characteristics of elite Taekwondo (TKD) players as well as their heart rate (HR) response and blood lactate concentration changes during TKD specific exercises and simulated competition.MethodsAnaerobic and aerobic power has been evaluated in eight elite TKD players (age: 20 ± 1 years, body mass: 70.8 ± 6 kg, Ht: 179.9 ± 4 cm). We also measured heart rate and blood lactate concentration during competition and specific-exercises (front kicks during 10 s, 1 and 3 min).ResultsMaximum oxygen uptake (VO₂max) and peak anaerobic power (Wpeak) averaged 56.22 ± 2.57 ml min^–1 kg^–1 and 12.1 ± 1.7 W kg^–1, respectively. HR and blood lactate [La] concentrations increased significantly during competition (F = 19.4, P < 0.001; F = 21.3, P < 0.001) compared to the resting value. HR and [La] values were significantly correlated with those measured during 10 s (R = 0.85, P < 0.05 and R = 0.79, P < 0.05, respectively) and 3-min specific exercises (R = 0.95, P < 0.01 and R = 0.76, P < 0.05).ConclusionsTKD requires high levels of both aerobic and anaerobic physical fitness. The correlation between specific exercises and competition is of practical interest for TKD players and trainers.     

Stride length–cadence relationship is disrupted in below-knee prosthesis users

The aim of this study was to evaluate the linearity of the relationship between stride length and cadence (STRIDE_LC) over three self-selected speeds (normal, slow, fast) in below-knee prosthesis users (n = 14, 11 men, mean age 43 ± 12 years, mean time since amputation 9.2 ± 6.9 years) in comparison to controls (n = 20, 11 men, mean age 43 ± 17 years). The step length–cadence relationship (STEP_LC) was also calculated for the prosthetic and intact legs in prosthesis users and compared to the dominant leg of controls. The goodness of linear fit (R²) and slope over 3 speeds were used as outcome measures. Prosthesis users walked significantly slower than controls (slow-fast speed means 82–131 vs. 97–169 cm/s, respectively, ANOVA p < 0.0001) due to both lower cadence (42–53 vs. 47–63 strides/min, p < 0.0001) and shorter stride length (116–149 vs. 123–161 cm, p < 0.0001). The R² of STRIDE_LC relationship in below-knee prosthesis users (0.76 ± 0.13) was significantly lower than in controls (0.91 ± 0.03, p < 0.001). The R² values of STEP_LC relationship between the prosthetic and intact legs in prosthesis users were correlated (r = 0.85, p < 0.001) and both (0.67 ± 0.19, 0.58 ± 0.21, respectively) were significantly smaller than in the dominant leg of controls (0.86 ± 0.04, p < 0.01). The slopes of STRIDE_LC and STEP_LC were not different. The R² of 0.84 for STRIDE_LC best discriminated prosthesis users from controls with high sensitivity (71%) and specificity (95%). The results indicate that coupling between stride/step length and cadence is disturbed in prosthesis users. Upon further investigation, the goodness of linear fit may prove to be useful in assessing prosthetic design, optimizing prosthetic fit, and predicting clinical outcomes.     

Effects of singular and dual task constraints on motor skill variability in childhood

We examined the effects of singular versus dual task constraints involving upper and lower extremities in typically developing children in young (4–6 years old), middle (7–9 years old), and old (10–13 years old) age groups. The purposes of this study were: 1) to investigate the effects of singular upper and lower extremity and dual upper and lower extremity conditions on motor variability and 2) to examine if variability in children’s motor actions would differ according to age (i.e., young, middle, or old). Twenty-four children (M age = 8.7; SD = 3.7) completed three tasks: finger rotation (upper extremity singular task constraint), obstacle crossing (lower extremity singular task constraint), and box carrying while walking (upper and lower extremity dual task constraint). Compared to the old age group, the young age group displayed more variable rotation strategies during clockwise (χ²(8, N = 24) = 12.4, p = 0.046) and counterclockwise finger rotation (χ²(8, N = 24) = 12.8, p = 0.047). During box carrying, children in the young age group had the most motor variability in their stride length, velocity, the vertical positioning of the box, and minimum and maximum joint excursion (all ps < 0.05). Crossing leg frontal plane hip angles were more variable on low versus high obstacles (all ps < 0.05). Our results suggest that four- to six-year-old children may still be developing the ability to produce consistent motor actions, especially under dual-task constraints. Examining children in the context of completing tasks with a variety of constraints may be useful in assessing the development of children's motor variability.     

Pancreatic adenocarcinoma: A simple CT score for predicting margin-positive resection in patients with resectable disease

BackgroundNegative-margin status is a prognostic indicator for long-term survival following curative intent resection for pancreatic adenocarcinoma. Patients at increased risk for positive-margin resections may benefit from neoadjuvant chemotherapy prior to resection.MethodsWe retrospectively analyzed preoperative computed-tomography (CT) scans in 108 consecutive patients that underwent curative intent resection for a resectable pancreatic ductal adenocarcinoma from 2009 to 2016 in two academic hospitals. Two radiologists independently staged the tumor, including tumor location, size, and tumor-to-superior mesenteric/portal vein (SMV/PV) contact. Uni and multivariate analysis were performed to identify independent predictors of an R1 resection.ResultsTwenty-nine patients had an R1 resection (26.9%). Tumor size, location, and presence of tumor-to-SMV/PV contact were significantly associated with an R1 resection. In multivariate analysis, the independent parameters associated with resection status were: tumor size (R² = 9.7), and tumor location (neck R² = 6.6; pancreaticoduodenal interface R² = 4.4; uncinate process R² = 4.1), but not tumor-to-SMV/PV contact (R² = 0.1, p = 0.7). A simple CT score was built based on tumor size and location. Patients with an R0 resectability score ≥3, i.e. patients with tumor size ≥30 mm (except when tumor location is at the pancreatico-duodenal interface) or patients with tumor size ≥20 mm AND tumor located in the uncinate process or neck, were at high-risk of an R1 resection (AUC, 0.82; sensitivity, 79%; specificity, 76%). This score also showed good diagnostic performances for predicting an R1 resection involving the medial resection margin only (AUC, 0.85).ConclusionsA simple score based on tumor location and size can accurately predict patients at high-risk of an R1 resection.     

Stature estimation in Japanese cadavers using the sacral and coccygeal length measured with multidetector computed tomography

We evaluated the relationship between stature and the length of the sacrum and coccyx using multidetector computed tomography (MDCT) and derived regression equations for stature estimation in the modern Japanese population. Two hundred and sixteen Japanese subjects (110 males and 106 females) who underwent postmortem computed tomography with subsequent forensic autopsy between January 2010 and August 2013 were measured. A sagittal-plane image of the sacrum and coccyx was used. Anterior sacral length (ASL) was defined as the linear distance from the anterosuperior edge of the first sacral vertebra (S1) to the anteroinferior edge of the fifth sacral vertebra (S5), and posterior sacral length (PSL) was defined as the linear distance from the posterosuperior edge of S1 to the anteroinferior edge of S5. Anterior sacrococcygeal length (ASCL) was defined as the linear distance from the anterosuperior edge of S1 to the anteroinferior edge of the last coccygeal vertebra (LCV), and posterior sacrococcygeal length (PSCL) was defined as the linear distance from the posterosuperior edge of S1 to the anteroinferior edge of the LCV. The correlation between stature and each parameter was evaluated by simple regression analysis using Pearson product-moment correlation coefficients. Each parameter was significantly and positively correlated with stature among both males and females. Cadaver stature (CS, cm) = 0.43 × PSL (mm) + 143.67 provided the most accurate stature prediction (R = 0.507, SEE = 5.83 cm) in males. CS (cm) = 0.56 × PSCL (mm) + 85.29 provided the most accurate stature prediction (R = 0.659, SEE = 6.68 cm) in females. We conclude that sacral/sacrococcygeal length measured with MDCT is a potentially useful tool for stature estimation, particularly in cases where better predictors such as the long bones are not available.     

Ageing and physical match performance in English Premier League soccer referees

Soccer referees are required to keep up with play at all times despite occupying an age bracket of on average 10–15 years older than their playing counterparts. Therefore, the aim of the present study was to examine the effect of age upon the physical match performances and match physiological loads of elite-level soccer referees. Match analysis data was collected (Prozone^®, Leeds, UK) from 22 professional soccer referees (age range 31–48 years) on FA Premier League matches over four consecutive seasons (778 observations). Physical match performance categories were total-distance covered (TD); high intensity running distance (speed >5.5 m s^?1, HIR); sprint count (>7.0 m s^?1, SC); top sprinting speed (TS); average distance from the ball (DB) and average distance from fouls (DF). Significant age effects were found for TD (r = ?0.52, p < 0.001), HIR (r = ?0.53, p < 0.001) and SC (r = ?0.53, p < 0.001). No age effect was found for DB and DF (p > 0.05). Despite covering less TD, HIR and performing fewer sprints the older referees (43–48 years) were able to maintain an average distance from fouls that was comparable to that recorded by the young (31–36 years) referees. Therefore, the reduced physical match performances associated with increasing referee age did not appear to impact upon the older referees’ ability to keep up with play. In light of these findings, refereeing governing bodies may wish to review their age-based retirement guidelines.     

Resectable pancreatic adenocarcinoma: Role of CT quantitative imaging biomarkers for predicting pathology and patient outcomes

BackgroundsPatients with a pancreatic cancer amenable to surgery still have a poor prognosis and high risk of post-operative recurrence. We aimed to assess the value of quantitative imaging biomarkers using computed-tomography (CT) texture analysis to evaluate the pathologic tumor aggressiveness and predict disease-free survival (DFS) in patients with resectable pancreatic adenocarcinoma.MethodsWe retrospectively performed attenuation measurements and texture analysis on the portal-venous phase of the pre-operative CT scan of 99 patients that underwent resection of a pancreatic ductal adenocarcinoma in two university hospitals. Tumor attenuation parameters included: mean attenuation value of the whole tumor (WHOLE-AV), and of the most hypoattenuating area within the tumor (CENTRAL-AV). Tumor heterogeneity parameters included: standard deviation, entropy, skewness, and kurtosis.ResultsTumor attenuation parameters showed significant association with the tumor differentiation grade (CENTRAL-AV, Odds ratio (OR) 0.968, 95% confidence interval (CI) 0.94–0.998) and lymph node invasion (WHOLE-AV, OR 0.886, CI 0.823–0.955). Variables associated with early-recurrence were: lymph node ratio (R² = 0.15), kurtosis (R² = 0.08), and CENTRAL-AV (R² = 0.04). Lymph node ratio (Hazard ratio (HR) 1.02), and CENTRAL-AV (HR 0.98) were independently associated with shorter DFS. Patients with CENTRAL-AV < 62 Hounsfield units had a shorter 1-year DFS (35% versus 68%, p = 0.004).ConclusionTumors that are more hypoattenuating on the portal-venous phase on CT scan are potentially more aggressive with higher tumor grade, greater lymph node invasion, and shorter DFS.