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Concept: Spearman's rank correlation coefficient

176

Human umbilical tissue-derived cells (hUTC) represent an attractive cell source and a potential technology for neurorestoration and improvement of functional outcomes following stroke. Male Wistar rats were subjected to a transient middle cerebral artery occlusion (tMCAo) and were intravenously administered hUTC (N = 11) or vehicle (N = 10) 48 hrs after stroke. White matter and vascular reorganization was monitored over a 12-week period using MRI and histopathology. MRI results were correlated with neurological functional and histology outcomes to demonstrate that MRI can be a useful tool to measure structural recovery after stroke. MRI revealed a significant reduction in the ventricular volume expansion and improvement in cerebral blood flow (CBF) in the hUTC treated group compared to vehicle treated group. Treatment with hUTC resulted in histological and functional improvements as evidenced by enhanced expression of vWF and synaptophysin, and improved outcomes on behavioral tests. Significant correlations were detected between MRI ventricular volumes and histological lesion volume as well as number of apoptotic cells. A positive correlation was also observed between MRI CBF or cerebral blood volume (CBV) and histological synaptic density. Neurological functional tests were also significantly correlated with MRI ventricular volume and CBV. Our data demonstrated that MRI measurements can detect the effect of hUTC therapy on the brain reorganization and exhibited positive correlation with histological measurements of brain structural changes and functional behavioral tests after stroke. MRI ventricular volumes provided the most sensitive index in monitoring brain remodeling and treatment effects and highly correlated with histological and functional measurements.

Concepts: Medicine, Brain, Blood, Spearman's rank correlation coefficient, Traumatic brain injury, Cerebrum, Correlation and dependence, Pearson product-moment correlation coefficient

169

BACKGROUND: Misreporting food intake is common because most health screenings rely on self-reports. The more accurate methods (eg, weighing food) are costly, time consuming, and impractical. OBJECTIVES: We developed a new instrument for reporting food intake-an Internet-based interactive virtual food plate. The objective of this study was to validate this instrument’s ability to assess lunch intake. METHODS: Participants were asked to compose an ordinary lunch meal using both a virtual and a real lunch plate (with real food on a real plate). The participants ate their real lunch meals on-site. Before and after pictures of the composed lunch meals were taken. Both meals included identical food items. Participants were randomized to start with either instrument. The 2 instruments were compared using correlation and concordance measures (total energy intake, nutritional components, quantity of food, and participant characteristics). RESULTS: A total of 55 men (median age: 45 years, median body mass index [BMI]: 25.8 kg/m(2)) participated. We found an overall overestimation of reported median energy intake using the computer plate (3044 kJ, interquartile range [IQR] 1202 kJ) compared with the real lunch plate (2734 kJ, IQR 1051 kJ, P<.001). Spearman rank correlations and concordance correlations for energy intake and nutritional components ranged between 0.58 to 0.79 and 0.65 to 0.81, respectively. CONCLUSION: Although it slightly overestimated, our computer plate provides promising results in assessing lunch intake.

Concepts: Nutrition, Spearman's rank correlation coefficient, Mass, Food, Interquartile range, Body mass index, Meal, Lunch

169

An important problem in systems biology is to reconstruct gene regulatory networks (GRNs) from experimental data and other a priori information. The DREAM project offers some types of experimental data, such as knockout data, knockdown data, time series data, etc. Among them, multifactorial perturbation data are easier and less expensive to obtain than other types of experimental data and are thus more common in practice. In this article, a new algorithm is presented for the inference of GRNs using the DREAM4 multifactorial perturbation data. The GRN inference problem among [Formula: see text] genes is decomposed into [Formula: see text] different regression problems. In each of the regression problems, the expression level of a target gene is predicted solely from the expression level of a potential regulation gene. For different potential regulation genes, different weights for a specific target gene are constructed by using the sum of squared residuals and the Pearson correlation coefficient. Then these weights are normalized to reflect effort differences of regulating distinct genes. By appropriately choosing the parameters of the power law, we constructe a 0-1 integer programming problem. By solving this problem, direct regulation genes for an arbitrary gene can be estimated. And, the normalized weight of a gene is modified, on the basis of the estimation results about the existence of direct regulations to it. These normalized and modified weights are used in queuing the possibility of the existence of a corresponding direct regulation. Computation results with the DREAM4 In Silico Size 100 Multifactorial subchallenge show that estimation performances of the suggested algorithm can even outperform the best team. Using the real data provided by the DREAM5 Network Inference Challenge, estimation performances can be ranked third. Furthermore, the high precision of the obtained most reliable predictions shows the suggested algorithm may be helpful in guiding biological experiment designs.

Concepts: DNA, Gene expression, Statistics, Spearman's rank correlation coefficient, Correlation and dependence, Pearson product-moment correlation coefficient, Regulation, Gene regulatory network

168

The aim of this study was to quantify anteroposterior facial soft tissue changes with respect to underlying skeletal movements after Le Fort I maxillary advancement and mandibular setback surgery with sagittal split osteotomy in Class III skeletal deformity by using lateral cephalograms taken before and after the operation. The material consisted of 31 patient (15 female, 16 male cases, mean age was 26.7 ± 2.5 years) with Class III skeletal deformity. All patients were treated by Le Fort I maxillary advancement and mandibular setback surgery with sagittal split osteotomy. Lateral cephalograms were taken before and 1.4 ± 0.3 years after surgery. Wilcoxon test was used to compare the pre- and post-surgical measurements. Pearson correlation test was used to compare the relationships between the skeletal, dental and facial soft tissue changes. In the maxilla, the APOINTAP (the anteroposterior position of A point) and ITIPAP (the anteroposterior position of upper incisor) showed significant protractions (-3.19 ± 3.63, and -3.19 ± 4.52, p < 0.01). In the mandible, the L1TIPAP (the anteroposterior position of lower incisor, -3.20 ± 5.83, p < 0.01), L1TIPSI (the superoinferior position of lower incisor, -2.43 ± 10.31, p < 0.05), BPOINTSP (the superoinferior position of B point, -2.28 ± 12.51, p < 0.05) and BPOINTAP (the anteroposterior position of B point, -3.19 ± 9.31, p < 0.01) showed significant retractions and upper positions after bimaxillary surgery. The insignificant decrease in soft tissue Pog-Vert distance was correlated the significant upper position of B point and lower incisor (r: 0.851, p < 0.001 and r: 0.842, p < 0.001).

Concepts: Spearman's rank correlation coefficient, Mandible, Tissues, Correlation and dependence, Pearson product-moment correlation coefficient, Soft tissue, Karl Pearson, Maxilla

167

PURPOSE: Existing patient self-reported shoulder scoring systems fail to express physicians' points of view, and understanding the wording can sometimes lead to confusion in Easterners. We sought to develop a valid, reliable, and responsive shoulder scoring system that combines the points of view of physicians and patients and is easily understood for worldwide applicability. METHODS: Six steps were followed to develop the scale: (1) investigation, identification of a specific population, and patient and physician interviews; (2) item generation, according to existing shoulder scales, a literature review, and patient and physician interviews; (3) item reduction, by combining and adjusting items; (4) formatting of the questionnaire, designed using both subjective and objective scales, with a 100-point score range; (5) pretesting, to eliminate confusion and misunderstanding of items, and (6) preliminary evaluation. Pearson correlation coefficients were calculated to assess validity (compared with American Shoulder and Elbow Surgeons, Constant-Murley, and University of California, Los Angeles scores), intraclass correlation coefficients were calculated to assess reliability (with a 2-week test-retest interval), and the standardized response mean was calculated to assess responsiveness (comparing preoperative and postoperative scores in patients). RESULTS: The final scoring system was designed to have a 100-point score range, with higher scores indicating better function. It consisted of self-report assessment by patients (61 points in total) and objective assessment by physicians (39 points in total). Updated scales, including a night pain subscale, patient-physician satisfaction, and 2-dimensional visual analog scale tool, were incorporated in our system. Compared with the other 3 scoring systems (American Shoulder and Elbow Surgeons, Constant-Murley, and University of California, Los Angeles scores), the new scoring system has shown favorable validity, with a Pearson correlation coefficient greater than 0.7. In addition, the intraclass correlation coefficient was greater than 0.9 during a 2-week test-retest interval, indicating high reliability, and the standardized response mean of the new system was greater than that of the other 3 scoring systems, indicating sensitive responsiveness. CONCLUSIONS: A new shoulder scoring system has been developed based on patients' and physicians' points of view and worldwide applicability and was verified to be valid, reliable, and responsive. The new scoring system includes a 2-dimensional visual analog scale, night pain subscale, and patient-physician satisfaction scale, which are not included in the existing scoring systems. LEVEL OF EVIDENCE: Level III, development of diagnostic criteria.

Concepts: Spearman's rank correlation coefficient, Physician, Assessment, Psychometrics, Correlation and dependence, Reliability, Pearson product-moment correlation coefficient, Covariance and correlation

166

Dietary iron absorption is regulated by hepcidin, an iron regulatory protein produced by the liver. Hepcidin production is regulated by iron stores, erythropoiesis and inflammation, but its physiology has not been characterized when repeated blood loss occurs. Hepcidin was measured in plasma samples obtained from 114 first-time/reactivated (no blood donations in prior 2 years) female donors and 34 frequent (≥3 red blood cell donations in prior 12 months) male donors as they were phlebotomized ≥4 or more times over 18-24 months. Hepcidin was compared to ferritin and hemoglobin using multivariable repeated measures regression models. Hepcidin, ferritin and hemoglobin declined with increasing frequency of donation in the first-time/reactivated females. Hepcidin and ferritin correlated well with each other (Spearman correlation of 0.74), but on average hepcidin varied more between donations for a given donor relative to ferritin. In a multivariable repeated measures regression model the predicted inter-donation decline in hemoglobin varied as a function of hepcidin and ferritin; hemoglobin was 0.51 g/dL lower for subjects with low (≤45.7 ng/ml) or decreasing hepcidin and low ferritin (≤26 ng/ml), and was essentially zero for other subjects including those with high (>45.7 ng/ml) or increasing hepcidin and low ferritin (≤26 ng/ml) (p<0.001). Hepcidin rapidly changes in response to dietary iron needed for erythropoiesis. The dynamic regulation of hepcidin in the presence of low ferritin suggests that plasma hepcidin may provide clinically useful information about an individual's iron status (and hence capacity to tolerate repeated blood donations) beyond that of ferritin alone.

Concepts: Hemoglobin, Blood, Red blood cell, Spearman's rank correlation coefficient, Liver, Anemia, Hematology, Iron deficiency anemia

166

We introduce a novel computational framework to enable automated identification of texture and shape features of lesions on (18)F-FDG-PET images through a graph-based image segmentation method. The proposed framework predicts future morphological changes of lesions with high accuracy. The presented methodology has several benefits over conventional qualitative and semi-quantitative methods, due to its fully quantitative nature and high accuracy in each step of (i) detection, (ii) segmentation, and (iii) feature extraction. To evaluate our proposed computational framework, thirty patients received 2 (18)F-FDG-PET scans (60 scans total), at two different time points. Metastatic papillary renal cell carcinoma, cerebellar hemongioblastoma, non-small cell lung cancer, neurofibroma, lymphomatoid granulomatosis, lung neoplasm, neuroendocrine tumor, soft tissue thoracic mass, nonnecrotizing granulomatous inflammation, renal cell carcinoma with papillary and cystic features, diffuse large B-cell lymphoma, metastatic alveolar soft part sarcoma, and small cell lung cancer were included in this analysis. The radiotracer accumulation in patients' scans was automatically detected and segmented by the proposed segmentation algorithm. Delineated regions were used to extract shape and textural features, with the proposed adaptive feature extraction framework, as well as standardized uptake values (SUV) of uptake regions, to conduct a broad quantitative analysis. Evaluation of segmentation results indicates that our proposed segmentation algorithm has a mean dice similarity coefficient of 85.75±1.75%. We found that 28 of 68 extracted imaging features were correlated well with SUV(max) (p<0.05), and some of the textural features (such as entropy and maximum probability) were superior in predicting morphological changes of radiotracer uptake regions longitudinally, compared to single intensity feature such as SUV(max). We also found that integrating textural features with SUV measurements significantly improves the prediction accuracy of morphological changes (Spearman correlation coefficient = 0.8715, p<2e-16).

Concepts: Cancer, Lung cancer, Non-small cell lung carcinoma, Spearman's rank correlation coefficient, Types of cancer, Squamous cell carcinoma, Correlation and dependence, Small cell carcinoma

166

BACKGROUND: Little evidence is available for the validity of dietary fish and polyunsaturated fatty acid intake derived from interviewer-administered questionnaires and plasma docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) concentration. METHODS: We estimated the correlation of DHA and EPA intake from both questionnaires and biochemical measurements. Ethnic Chinese adults with a mean (+/- SD) age of 59.8 (+/-12.8) years (n = 297) (47% women) who completed a 38-item semi-quantitative food-frequency questionnaire and provided a plasma sample were enrolled. Plasma fatty acids were analyzed by capillary gas chromatography. RESULTS: The Spearmen rank correlation coefficients between the intake of various types of fish and marine n-3 fatty acids as well as plasma DHA were significant, ranging from 0.20 to 0.33 (P < 0.001). In addition, dietary EPA, C22:5 n-3 and DHA were significantly correlated with the levels of marine n-3 fatty acids and DHA, with the Spearman rank correlation coefficients ranging from 0.26 to 0.35 (P < 0.001). Moreover, compared with those in the lowest fish intake quintile, participants in the highest quintile had a significantly higher DHA level (adjusted mean difference, 0.99 +/- 0.10%, test for trend, P < 0.001). Similar patterns between dietary DHA intake and plasma DHA levels were found. However, the association between dietary fish intake and plasma EPA was not significant (test for trend, P = 0.69). CONCLUSIONS: The dietary intakes of fish and of long chain n-3 fatty acids, as determined by the food frequency questionnaire, were correlated with the percentages of these fatty acids in plasma, and in particular with plasma DHA. Plasma DHA levels were correlated to dietary intake of long-chain n-3 fatty acids.

Concepts: Nutrition, Fatty acids, Spearman's rank correlation coefficient, Essential fatty acid, Omega-3 fatty acid, Eicosapentaenoic acid, Docosahexaenoic acid, Butyric acid

151

The purpose of this prospective study was to establish the ultrasonographic characteristics of the dimension of the right pancreatic lobe with that of the associated anatomic landmarks in healthy dogs. Ultrasonographic examinations were performed on 25 dogs. The thickness of the right pancreatic lobe was compared with that of mural thickness of duodenum, diameters of duodenum, pancreatic duct, abdominal aorta, portal vein, caudal vena cava, and length and width of the right kidney and right adrenal gland. The correlation between each pancreatic parameter and the dimensions of the anatomical landmarks were assessed using linear regression analysis and Pearson’s correlation coefficient ® test. Significant, but weak linear correlations were observed between thickness of right pancreatic lobe with that of duodenum mural thickness (r=0.605, R(2)=0.339, P=0.001); duodenum diameter (r=0.573, R(2)=0.299, P=0.003); and right adrenal gland length (r=0.508, R(2)=0.052, P=0.01). There was no significant dimensional relationship with other selected anatomic landmarks. The ratio between the thickness of right pancreatic lobe and the mural thickness of duodenum, diameter of duodenum and length of right adrenal gland were 2.88 ± 0.53, 1.27 ± 0.27, and 0.81 ± 0.15, respectively. Calculating the ratio of thickness of the right pancreatic lobe with the dimension of significantly correlated anatomic landmarks is a useful and simple method for evaluating the size of the right pancreatic lobe in dogs in clinical practice.

Concepts: Kidney, Pancreas, Spearman's rank correlation coefficient, Abdominal aorta, Correlation and dependence, Pearson product-moment correlation coefficient, Covariance and correlation, Adrenal gland

61

Accumulating evidence indicates high risk of bias in preclinical animal research, questioning the scientific validity and reproducibility of published research findings. Systematic reviews found low rates of reporting of measures against risks of bias in the published literature (e.g., randomization, blinding, sample size calculation) and a correlation between low reporting rates and inflated treatment effects. That most animal research undergoes peer review or ethical review would offer the possibility to detect risks of bias at an earlier stage, before the research has been conducted. For example, in Switzerland, animal experiments are licensed based on a detailed description of the study protocol and a harm-benefit analysis. We therefore screened applications for animal experiments submitted to Swiss authorities (n = 1,277) for the rates at which the use of seven basic measures against bias (allocation concealment, blinding, randomization, sample size calculation, inclusion/exclusion criteria, primary outcome variable, and statistical analysis plan) were described and compared them with the reporting rates of the same measures in a representative sub-sample of publications (n = 50) resulting from studies described in these applications. Measures against bias were described at very low rates, ranging on average from 2.4% for statistical analysis plan to 19% for primary outcome variable in applications for animal experiments, and from 0.0% for sample size calculation to 34% for statistical analysis plan in publications from these experiments. Calculating an internal validity score (IVS) based on the proportion of the seven measures against bias, we found a weak positive correlation between the IVS of applications and that of publications (Spearman’s rho = 0.34, p = 0.014), indicating that the rates of description of these measures in applications partly predict their rates of reporting in publications. These results indicate that the authorities licensing animal experiments are lacking important information about experimental conduct that determines the scientific validity of the findings, which may be critical for the weight attributed to the benefit of the research in the harm-benefit analysis. Similar to manuscripts getting accepted for publication despite poor reporting of measures against bias, applications for animal experiments may often be approved based on implicit confidence rather than explicit evidence of scientific rigor. Our findings shed serious doubt on the current authorization procedure for animal experiments, as well as the peer-review process for scientific publications, which in the long run may undermine the credibility of research. Developing existing authorization procedures that are already in place in many countries towards a preregistration system for animal research is one promising way to reform the system. This would not only benefit the scientific validity of findings from animal experiments but also help to avoid unnecessary harm to animals for inconclusive research.

Concepts: Scientific method, Critical thinking, Statistics, Mathematics, Spearman's rank correlation coefficient, Academic publishing, Experiment, Peer review