Application of Microhaplotypes in Sibling Kinship Testing / 法医学杂志

OBJECTIVES@#To investigate the efficacy of different numbers of microhaplotype (MH) loci and the introduction of different reference samples on the identification of full sibling, half sibling and differentiation between full sibling and half sibling kinships, and to explore the effect of changing mutation rate on sibling testing.@*METHODS@#First, a family map involving three generations was established, and four full sibling identification models, five half sibling identification models and five models distinguishing full and half siblings were constructed for different reference samples introduced. Based on the results of the previous study, two sets of nonbinary SNP-MH containing 34 and 54 loci were selected. Based on the above MH loci, 100 000 pairs of full sibling vs. unrelated individuals, 100 000 pairs of half sibling vs. unrelated individuals and 100 000 pairs of full sibling vs. half sibling were simulated based on the corresponding sibling kinship testing models, and the efficacy of each sibling kinship testing model was analyzed by the likelihood ratio algorithm under different thresholds. The mutant rate of 54 MH loci was changed to analyze the effect of mutation rate on sibling identification.@*RESULTS@#In the same relationship testing model, the systematic efficacy of sibling testing was positively correlated with the number of MH loci detected. With the same number of MH loci, the efficacy of full sibling testing was better than that of uncle or grandfather when the reference sample introduced was a full sibling of A, but there was no significant difference in the identification efficacy of the four reference samples introduced for full sibling and half sibling differentiation testing. In addition, the mutation rate had a slight effect on the efficacy of sibling kinship testing.@*CONCLUSIONS@#Increasing the number of MH loci and introducing reference samples of known relatives can increase the efficacy of full sibling testing, half sibling testing, and differentiation between full and half sibling kinships. The level of mutation rate in sibling testing by likelihood ratio method has a slight but insignificant effect on the efficacy.

Calculation of Likelihood Ratios for Incest Cases Using IBD Patterns / 法医学杂志

OBJECTIVES@#To calculate the likelihood ratios of incest cases using identity by descent (IBD) patterns.@*METHODS@#The unique IBD pattern was formed by denoting the alleles from the members in a pedigree with a same digital. The probability of each IBD pattern was obtained by multiplying the prior probability by the frequency of non-IBD alleles. The pedigree likelihoods of incest cases under different hypotheses were obtained by summing all IBD pattern probabilities, and the likelihood ratio(LR) was calculated by comparing the likelihoods of different pedigrees.@*RESULTS@#The IBD patterns and the formulae of calculating LR for father-daughter incest and brother-sister incest were obtained.@*CONCLUSIONS@#The calculations of LR for incest cases were illustrated based on IBD patterns.

Calculation of the Paternity Index for the Alleged Father Related to the Child's Mother / 法医学杂志

OBJECTIVES@#To derive the paternity index (PI) calculation formula of the alleged father (AF) when the AF is a relative (parent/child, siblings, grandparent/grandchild, uncle/nephew, first cousins) of the child's biological mother.@*METHODS@#For the case when the AF is related to the child's biological mother, the existence of the relationship in the numerator and denominator hypothesis of PI was considered. The genotype frequency of the AF was calculated by using the frequency formula in which the mother's genotype was considered, while the random male in the denominator was substituted as another relative of the mother's same rank. The PI calculation formula was derived to eliminate the effect of the relationship between AF and the child's biological mother.@*RESULTS@#When the AF and the biological mother have first, second and tertiary kinship, a more conservative PI was obtained from the PI calculation formula derived in this study compared with the PI calculation method which did not consider kinship.@*CONCLUSIONS@#The calculation method provided in this study can eliminate the effect of the relation of the AF and mother on the PI in incest cases, to obtain more accurate and conservative identification conclusions.

Identification Strategy of Biological Half Sibling Relationship / 法医学杂志

OBJECTIVES@#To compare the application value of the likelihood ratio (LR) method and identity by state (IBS) method in the identification involving half sibling relationships, and to provide a reference for the setting of relevant standards for identification of half sibling relationship.@*METHODS@#(1) Based on the same genetic marker combinations, the reliability of computer simulation method was verified by comparing the distributions of cumulated identity by state score (CIBS) and combined full sibling index in actual cases with the distributions in simulated cases. (2) In different numbers of three genetic marker combinations, the simulation of full sibling, half sibling and unrelated individual pairs, each 1 million pairs, was obtained; the CIBS, as well as the corresponding types of cumulative LR parameters, were calculated. (3) The application value of LR method was compared with that of IBS method, by comparing the best system efficiency provided by LR method and IBS method when genetic markers in different amounts and of different types and accuracy were applied to distinguish the above three relational individual pairs. (4) According to the existing simulation data, the minimum number of genetic markers required to distinguish half siblings from the other two relationships using different types of genetic markers was estimated by curve fitting.@*RESULTS@#(1) After the rank sum test, under the premise that the real relationship and the genetic marker combination tested were the same, there was no significant difference between the simulation method and the results obtained in the actual case. (2) In most cases, under the same conditions, the system effectiveness obtained by LR method was greater than that by IBS method. (3) According to the existing data, the number of genetic markers required for full-half siblings and half sibling identification could be obtained by curve fitting when the system effectiveness reached 0.95 or 0.99.@*CONCLUSIONS@#When distinguishing half sibling from full sibling pairs or unrelated pairs, it is recommended to give preference to the LR method, and estimate the required number of markers according to the identification types and the population data, to ensure the identification effect.

Methods and Research Hotspots of Forensic Kinship Testing / 法医学杂志

Kinship testing is widely needed in forensic science practice. This paper reviews the definitions of common concepts, and summarizes the basic principles, advantages and disadvantages, and application scope of kinship analysis methods, including identity by state (IBS) method, likelihood ratio (LR) method, method of moment (MoM), and identity by descent (IBD) segment method. This paper also discusses the research hotspots of challenging kinship testing, complex kinship testing, forensic genetic genealogy analysis, and non-human biological samples.

Added value of PET Bayesian penalized likelihood reconstruction algorithm in the diagnosis of solitary pulmonary nodules/masses / 中华核医学与分子影像杂志

Objective:To investigate the effects of silicon photomutipliers (SiPM) detector and Bayesian penalized likelihood (BPL) reconstruction algorithm on semiquantitative parameters of 18F-FDG PET/CT and diagnostic efficiency for solitary pulmonary nodules/masses compared with traditional photomultiplier tube (PMT) and ordered subsets expectation maximization (OSEM). Methods:From March 2020 to January 2022, 118 patients (76 males, 42 females, age (63.0±10.1) years) newly diagnosed with solitary pulmonary nodules/masses in First Hospital of Shanxi Medical University were prospectively enrolled and underwent 18F-FDG PET/CT imaging with two different PET/CT scanners successively. The images were divided into PMT+ OSEM, SiPM+ OSEM and SiPM+ BPL groups according to PET detector and reconstruction algorithms. The SUV max, SUV mean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of pulmonary nodules/masses were measured, then signal-to-noise ratio (SNR) and signal-to-background ratio (SBR) were calculated. One-way analysis of variance and Kruskal-Wallis rank sum test were performed to compare differences of above parameters among groups. ROC curve analysis was used to analyze the optimal threshold of SUV max for the differential diagnosis of pulmonary nodules/masses and AUCs were obtained. Results:There were 83 malignant nodules and 35 benign nodules. The image quality of SiPM+ BPL group (4.23±0.64) was better than that of SiPM+ OSEM group (3.57±0.50) or PMT+ OSEM group (3.58±0.51; F=54.85, P<0.001). There were significant differences in SUV max (7.57(3.86, 15.61) vs 4.95(2.22, 10.48)), SUV mean (4.43(2.28, 9.12) vs 2.84(1.21, 5.71)), MTV (3.54(1.57, 7.67) vs 5.09(2.83, 11.79)), SNR (28.12(12.55, 54.38) vs 20.16(8.29, 41.45)) and SBR (4.03(1.83, 7.75) vs 2.32(0.96, 5.03)) between SiPM+ BPL and SiPM+ OSEM groups ( H values: 16.63-37.05, all P<0.001). The optimal threshold values of SUV max in SiPM+ BPL, SiPM+ OSEM and PMT+ OSEM were 3.31, 2.21, 2.05 with AUCs of 0.686, 0.689, 0.615 for nodules < 2 cm, and were 10.29, 6.49, 4.33 with AUCs of 0.775, 0.782, 0.774 for nodules/masses ≥2 cm. Conclusions:Image quality and parameters of pulmonary nodules/masses are mainly affected by the reconstruction algorithms. BPL can improve SUV max, SUV mean, SBR and SNR, but reduce MTV without significant effect on liver parameters. SiPM+ BPL has a higher diagnostic threshold of SUV max than SiPM+ OSEM and PMT+ OSEM.

Interobserver agreement and diagnostic performance assessment of clear cell likelihood score using T 2WI with fat suppression technique / 中华放射学杂志

Objectives:To investigate the effect of fat suppression (FS) T 2WI on the interobserver agreement and diagnostic performance of clear cell likelihood score version 2.0 (ccLS v2.0) for clear cell renal cell carcinoma (ccRCC). Methods:In this retrospective study, the MR images of 111 patients with pathologically confirmed small renal masses (SRM) from January to December 2021 were analyzed in the First Medical Centre, Chinese PLA General Hospital. Of the 111 SRM, 82 cases were ccRCC and 29 cases were non-ccRCC. Two radiologists independently assessed ccLS scores based on T 2WI signal intensity (hypointense, isointense, hyperintense) and other MRI features (ccLS-T 2WI). After a one-month interval, the ccLS scores were independently evaluated utilizing the frequency-selective saturation FS-T 2WI and other MRI features (ccLS-FS-T 2WI). Fisher′s exact test was used to compare the difference in SRM signal intensity on T 2WI and FS-T 2WI. The weighted Kappa test was performed to assess the interobserver agreement of the two radiologists, and differences in the weighted Kappa coefficients were compared using the Gwet consistency coefficient. Receiver operating characteristic curves were drawn to evaluate the diagnostic performance of ccLS-T 2WI and ccLS-FS-T 2WI in diagnosing ccRCC, and the area under the curve (AUC) was compared utilizing the DeLong test. Results:The signal intensity of 111 SRM on T 2WI and FS-T 2WI had statistically significant difference (χ 2=126.33, P<0.001), consistent in 88 cases (79.3%) and varied in 23 cases (20.7%). The weighted Kappa coefficient of ccLS-T 2WI was 0.57 (95%CI 0.45-0.69) between the two radiologists, and the weighted Kappa coefficient of ccLS-FS-T 2WI was 0.55 (95%CI 0.42-0.67), and the difference was not statistically significant ( t=-0.65, P=0.520). The AUC of ccLS-T 2WI for ccRCC diagnosis was 0.92 (95%CI 0.86-0.97), while the AUC of ccLS-FS-T 2WI for ccRCC diagnosis was 0.91 (95%CI 0.85-0.96), and the difference was not statistically significant ( Z=1.50, P=0.133). Conclusions:The interobserver agreement and diagnostic performance of ccLS v2.0 based on T 2WI and FS-T 2WI sequences for ccRCC are comparable, and FS-T 2WI is applicable for the clinical application of ccLS v2.0.

Change point analysis of normal distribution based on the likelihood ratio principle and its application in the number of outpatients analysis / 中华地方病学杂志

Objective:The authors introduced the change point analysis of normal distribution based on the likelihood ratio principle, analyzed the number of outpatients in a hospital of Luohu District, Shenzhen, to provide scientific basis for rational allocation of health resources.Methods:The authors collected totally 636 number of outpatients' data from 8: 00 to 12: 00 a.m. at 48 time windows at 5 minutes intervals in a hospital of Luohu District, Shenzhen, and analyzed it with single change point analysis of simultaneous change of mean and variance, and discussed when the change point occurred.Results:The average number of outpatient was 13.250 0 for every time window, the change point occurred at 8: 50, the probability was 0.000 025, the average number of outpatient per 5 minutes from 8: 00 to 8: 50 was 7.000 0, the average number of outpatient per 5 minutes from 8: 50 to 12: 00 was 14.897 4, and the ratio of number of outpatients before and after the change point occurred was 1∶2.Conclusion:In the case of no need to determine the base period or compare the data, the change point analysis of normal distribution based on the principle of likelihood ratio provides a new way of statistical analysis and statistical monitoring for the rational allocation of health resources based on the number of patients.

Comparison of diagnostic performance of Clear Cell Likelihood Score v1.0 and v2.0 for clear renal cell carcinoma / 南方医科大学学报

OBJECTIVE@#To compare the performance of Clear Cell Likelihood Score (ccLS) v1.0 and v2.0 in diagnosing clear cell renal cell carcinoma (ccRCC) from small renal masses (SRM).@*METHODS@#We retrospectively analyzed the clinical data and MR images of patients with pathologically confirmed solid SRM from the First Medical Center of the Chinese PLA General Hospital between January 1, 2018, and December 31, 2021, and from Beijing Friendship Hospital of Capital Medical University and Peking University First Hospital between January 1, 2019 and May 17, 2021. Six abdominal radiologists were trained for use of the ccLS algorithm and scored independently using ccLS v1.0 and ccLS v2.0. Random- effects logistic regression modeling was used to generate plot receiver operating characteristic curves (ROC) to evaluate the diagnostic performance of ccLS v1.0 and ccLS v2.0 for ccRCC, and the area under curve (AUC) of these two scoring systems were compared using the DeLong's test. Weighted Kappa test was used to evaluate the interobserver agreement of the ccLS score, and differences in the weighted Kappa coefficients was compared using the Gwet consistency coefficient.@*RESULTS@#In total, 691 patients (491 males, 200 females; mean age, 54 ± 12 years) with 700 renal masses were included in this study. The pooled accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ccLS v1.0 for diagnosing ccRCC were 77.1%, 76.8%, 77.7%, 90.2%, and 55.7%, as compared with 80.9%, 79.3%, 85.1%, 93.4%, 60.6% with ccLS v2.0, respectively. The AUC of ccLS v2.0 was significantly higher than that of ccLS v1.0 for diagnosis of ccRCC (0.897 vs 0.859; P < 0.01). The interobserver agreement did not differ significantly between ccLS v1.0 and ccLS v2.0 (0.56 vs 0.60; P > 0.05).@*CONCLUSION@#ccLS v2.0 has better performance for diagnosing ccRCC than ccLS v1.0 and can be considered for use to assist radiologists with their routine diagnostic tasks.

Assessment of optic disk by disk damage likelihood scale staging using slit-lamp biomicroscopy and optical coherence tomography in diagnosing primary open-angle glaucoma

Purpose: The current study was aimed at assessment of optic disk by disk damage likelihood scale (DDLS) staging using slit?lamp biomicroscopy and optical coherence tomography (OCT) in diagnosing primary open?angle glaucoma (POAG) patients. Methods: This was a cross?sectional observational study of 106 POAG patients, which was conducted from April 2017 to April 2018. All patients underwent slit?lamp fundoscopy with a +78 D lens and high?definition (HD)?OCT, and the vertical cup disk ratios (VCDRs) were recorded. Disk size and neuroretinal rim assessment were done, and the disk was then staged using the recent version, which stages the optic nerve head (ONH) from 1 to 10 as read from the DDLS nomogram table. DDLS scores >5 indicate glaucomatous damage. Pearson coefficient was used to correlate the DDLS staging by slit?lamp biomicroscopy with best?corrected visual acuity (BCVA), intraocular pressure (IOP), disk size, and VCDR and VCDR, mean deviation, and DDLS staging by HD?OCT. Results: The mean age of the patients was 59.54 ± 6.61 years. The male: female ratio was 2:1. The mean IOP was 16.04 ± 1.97 mmHg, and BCVA was 0.72 ± 0.13 LogMAR units. The mean VCDR on 78 D slit?lamp biomicroscopy was 0.76 ± 0.09 (standard deviation [SD]) (range 0.1–0.77), whereas on HD?OCT, the mean VCDR was 0.81 ± 0.09 (SD) (range 0.07–0.81). The mean deviation on visual field testing in decibels was ?14.43 ± 3.31 (SD). The correlation coefficient between DDLS staging by slit?lamp biomicroscopy and DDLS staging by HD?OCT parameters was r = 0.96. Conclusion: There is a positive correlation between the DDLS system of optic disk evaluation on slit?lamp biomicroscopy and most of the HD?OCT evaluation parameters

Likelihood Ratio And Repertory: A Useful Tool To Update Our Repertories

Background:Homoeopathic Science is focusing on the scientific explanation regarding its medicinal action and prescriptions in language of Research and Methodology. Whenever the word Research is there in any area, statistics comes automatically for presentation of theresearch findings. Homoeopathy accepts various Statistical Methods in its research studies to show their efficacy in Medical Science. Likelihood ratio is one of the statistical tools that help Physicians to develop skill in diagnosis of the various disease conditions. In Homoeopathic Science, this tool is not only helpful in case management but also help us to update our Repertories with its scientific data obtained by various case studies. So, let’s explore this tool named Likelihood ratio and its utilityin Homoeopathic Tool named Repertory. Material And Methods:It is a type of analytical study with following inclusion and exclusion criteria.Inclusion criteria:Most frequently cited articles of likelihood ratio were included. Exclusion criteria: publications of article based on likelihood ratio before year 2000 AD were excluded from study.Result:Less than 9 articles with most frequent citation wereeligible for study. There was scarcityof data regarding likelihood ratio in Homoeopathic Science.Conclusion:Many research papersregarding utility of likelihood ratio and repertories are present in Homoeopathic world but still the concept is not able to put a great impact on Homoeopath’s mind.Acceptance of this tool may help us to improve our Homoeopathic practice as well as standards of our Homoeopathy in Medical Science.

Desempeño de biomarcadores de las imágenes con tensor de difusión en regiones tumorales del glioblastoma. Análisis exploratorio de datos mediante gráficos de zombie y pruebas de diagnóstico / Diffusion tensor imaging-derived biomarkers performance in glioblastoma tumor regions: exploratory data analysis using zombie plots and diagnostic tests

Resumen Introducción: Han sido reportados 11 biomarcadores de imágenes con tensor de difusión (DTI) en las regiones tumorales del glioblastoma. Objetivo: Comparar la eficacia de biomarcadores de glioblastoma mediante gráficos de zombie, que permiten la comparación simultánea en función de razones de verosimilitud. Métodos: Cohorte retrospectiva de 29 sujetos con glioblastoma a quienes se efectuó resonancia magnética cerebral de 3 T. Los eigenvalores mayor, intermedio y menor de ITD se utilizaron para calcular 11 biomarcadores en cinco regiones tumorales: sustancia blanca de apariencia normal (NAWM), edema proximal y distal, tumoral viable y necrosis. Las tablas de contingencia con resultados verdaderos y falsos positivos y negativos permitieron calcular gráficos de zombie basados en el factor de Bayes y pruebas diagnósticas previamente no reportadas. Resultados: Los biomarcadores DM, AF, q, L, Cl, Cp, AR actúan en la zona óptima para el diagnóstico de NAWM. Las regiones de edema proximal y distal, tejido tumoral que se realza con contraste y necrosis no poseen biomarcadores que las identifiquen en un nivel de rendimiento óptimo. Conclusiones: Los biomarcadores DM, AF, q, L, Cl, Cp, AR discriminan el tejido cerebral normal en la zona óptima, pero el rendimiento de otras regiones tumorales se ubica en las zonas de inclusión diagnóstica, exclusión diagnóstica y mediocre.

Abstract Introduction: Using diffusion tensor imaging (DTI), 11 biomarkers have been reported in different glioblastoma regions. Objective: To compare the efficacy of glioblastoma biomarkers using "zombie plots". Methods: Retrospective cohort of 29 subjects with glioblastoma who underwent 3-Tesla brain magnetic resonance imaging. DTI major, intermediate and minor eigenvalues were used to calculate biomarkers at five tumor regions: normal-appearing white matter (NAWM), proximal and distal edema, tumor tissue and necrosis. Contingency tables with true and false positive and negative results allowed the calculation of zombie plots based on the Bayes factor and previously unreported diagnostic tests. Results: The MD, FA, q, L, Cl, Cp and RA biomarkers had a good performance at the optimal zone for NAWM diagnosis. The proximal and distal edema, enhancing rim and necrosis regions do not have biomarkers that identify them with an optimal performance level. Conclusions: Zombie plots allow simultaneous comparison of biomarkers based on likelihood ratios. MD, FA, q, L, Cl, Cp, RA discriminated NAWM normal brain tissue at the optimal zone, but performance for other regions was at the mediocre, diagnostic inclusion and diagnostic exclusion zones.

Decisions on what diagnostic tests to request

@#In Evidence-based Family Practice, requesting a diagnostic test should be based on two issues. First is whether the test is accurate and thus will significantly help in clinical decision making. Second is whether the test is appropriate and acceptable for the patient. This involves careful discussion of risks and benefits based on the physician’s knowledge and experience and the patient’s values and preferences.

Distribution characteristics of choroidal thickness in normal population and the diagnostic cut-off value for pachychoroid / 中华实验眼科杂志

Objective:To characterize the distribution characteristics of choroidal thickness in healthy normal subjects and to define the diagnostic cut-off value for pachychoroid.Methods:A cross-sectional study design was carried out.Four hundred and forty-six eyes of 230 healthy subjects from the pachychoroid disease spectrum (PCD) cohort in Beijing Tongren Hospital from April 2018 to June 2021, were enrolled for the choroidal thickness distribution analysis.Three hundred and fourteen eyes of 274 patients with PCD including 149 eyes of 113 patients with central serous chorioretinopathy, 95 eyes of 81 patients with polypoid choroidal vasculopathy, 70 eyes of 60 patients with neovascular age-related macular degeneration, along with 382 eyes of 199 normal subjects matched for refractive error, age and gender with PCD were selected for likelihood ratio analysis.Routine eye examinations including the best corrected visual acuity, intraocular pressure, slit-lamp microscopy, dilated fundus examination and color fundus photography were performed in all subjects.Swept-source optical coherence tomography (SS-OCT) of 9 mm×9 mm scanning mode was used to measure the subfoveal choroidal thickness (SFCT) automatically in nine macular regions according to the Early Treatment Diabetic Retinopathy Study classification system using TOPCON Advanced Boundary Segmentation (TABS) software.Pearson linear correlation analysis and Spearman rank correlation analysis were adopted to evaluate the correlations between SFCT and age, diopter.Multiple linear regression was employed to analyze the factors affecting SFCT.After age and refractive error adjustment, the likelihood ratio test was used to determine the diagnostic cut-off value for pachychoroid.This study adhered to the Declaration of Helsinki.The study protocol was approved by an Ethics Committee of Beijing Tongren Hospital (No.TRECKY2016-054). Written informed consent was obtained from each subject prior to entering the cohort.Results:A negative correlation was found between SFCT and age in normal eyes ( r=-0.34, P<0.001), in both normal male and female subjects ( r=-0.43, P<0.001; r=-0.38; P<0.001). A weak positive correlation was found between SFCT and diopter ( rs=0.19, P<0.001). It was found that age and diopter were strongly correlated with SFCT (both at P<0.001). The cut-off values for pachychoroid in 20-39 years group, 40-59 years group, 60-79 years group and ≥80 years group were 320-330 μm, 330-340 μm, 250-275 μm and 200-225 μm, respectively.The percentages of eyes with pachychoroid in 20-39 years group, 40-59 years group and ≥60 years group were 14.71%(10/68), 24.48%(47/192) and 28.89%(55/184), respectively, showing statistically significant differences among them ( χ2=6.170, P=0.046; LR=6.579, P=0.037). The proportion of pachychoroid in ≥60 years group was significantly higher than that of 20-39 years group, showing a statistically significant difference ( χ2=5.982, P=0.014; LR=6.479, P=0.011). Conclusions:The distribution characteristics of pachychoroid vary in normal subjects over age.Age and diopter are the independent influencing factors of SFCT.

Key technology and multi-directional decomposition method of the causal mediation effect analysis / 四川精神卫生

The purpose of this paper was to introduce five key techniques and the multi-directional decomposition methods of effect components in the analysis of causal mediation effects. The contents of the five key technologies were as follows： ① identification of causal mediation effect； ② regression method of causal mediation effect analysis； ③ maximum likelihood estimation； ④ estimation of total effect and various component effects； ⑤ estimation by bootstrap method. The multi-directional decomposition methods included 3 bidirectional decompositions， 2 three-directional decompositions and 1 four-directional decomposition. Through an example， a causal mediation effect analysis model including covariates and interaction terms was constructed with the help of SAS， bidirectional decomposition， three-directional decomposition and four-directional decomposition were carried out for the total effect in the causal mediation effect analysis， and the output results were explained.

Niveles de ferritina en artritis idiopática juvenil de inicio sistémico comparada con otras fiebres de origen desconocido: estudio multicéntrico de pruebas diagnósticas / Ferritin levels in children with juvenile idiopathic arthritis of systemic onset and children with other causes of fever of unknown origin: A multicenter study of diagnostic tests

Resumen | Introducción. No se dispone de pruebas sensibles ni específicas para diagnosticar la artritis idiopática juvenil sistémica. Objetivo. Evaluar la utilidad diagnóstica de niveles de ferritina total cinco veces por encima del valor normal (ferritina total>5N) y el porcentaje disminuido (menor de o igual a 20 % de la ferritina total) de la ferritina glucosilada (ferritina glucosilada<20 %) para el diagnóstico de artritis idiopática juvenil sistémica en pacientes con fiebre de origen desconocido evaluados por reumatología pediátrica. Materiales y métodos. Se hizo un estudio observacional de pruebas diagnósticas de corte transversal en menores de 16 años hospitalizados entre el 2010 y el 2014. El patrón diagnóstico de referencia fue el cumplimiento de los criterios de clasificación o diagnóstico confirmado en el seguimiento. Se determinaron las medidas de utilidad de las pruebas. Resultados. Se incluyeron 40 pacientes con fiebre de origen desconocido: 11 con artritis idiopática juvenil sistémica y 29 con otros diagnósticos. La mediana de la ferritina total fue mayor en la artritis idiopática juvenil sistémica (3.992 ng/ml) comparada con otras causas de fiebre de origen desconocido (155 ng/ml) (p=0,0027), así como la ferritina total>5N (90,91 % Vs. 51,72 %) (p=0,023). El porcentaje de ferritina glucosilada≤20 % fue de 96,5 % en otras fiebres de origen desconocido en comparación con la artritis idiopática juvenil sistémica (81,8 %) (p=0,178). La ferritina total>5N tuvo una sensibilidad del 91 %, una especificidad del 48 %; un cociente de probabilidades (Likelihood Ratio, LR) positivo de 1,76 y uno negativo de 0,19, demostrando mayor utilidad para el diagnóstico que la combinación de la ferritina total>5N y ferritina glucosilada≤20 %, cuya sensibilidad fue del 81,8 %, la especificidad del 48,3 %, un cociente de probabilidades LR positivo de 1,58 y un LR negativo de 0,38. Conclusión. En pacientes con fiebre de origen desconocido evaluados por reumatología pediátrica, la ferritina total>5N demostró ser útil como prueba de tamización para el diagnóstico de artritis idiopática juvenil sistémica.

Abstract | Introduction: There are no sensitive or specific tests available to diagnose systemic juvenile idiopathic arthritis (sJIA). Objective: To assess the utility as diagnostic tests of total ferritin (TF) levels greater than 5 times the normal value (TF>5N) and the decreased percentage (less than or equal to 20% of TF) of glycosylated ferritin (GF≤20%) for the diagnosis of sJIA in patients with fever of unknown origin evaluated by pediatric rheumatology. Materials and methods: We conducted an observational, cross-sectional study of diagnostic tests in children under 16 years of age hospitalized between 2010 and 2014. The reference diagnostic standard was the fulfillment of the classification criteria or confirmed diagnosis at follow-up. We determined the measures of utility of the tests. Results: We included 40 patients with fever of unknown origin, 11 with sJIA, and 29 with other diagnoses. The median TF was higher in sAIJ (3992 ng/ml) versus other causes of fever of unknown origin (155 ng/ml) (p=0.0027), as well as TF>5N (90.91% versus 51.72%) (p=0.023). The percentage of GF≤20% was higher in patients with other causes of fever of unknown origin (96.5%) compared to sJIA (81.8%) (p=0.178). TF>5N had a sensitivity of 91%, specificity of 48%, positive likelihood ratio (LR) of 1.76, and negative LR of 0.19 demonstrating greater utility for the diagnosis of sJIA than the combination of FT> 5N with GFR <20%, with a sensitivity of 81.8%, specificity of 48.3%, positive LR of 1.58, and negative LR of 0.38. Conclusion: In patients with FUO evaluated by pediatric rheumatology, TF> 5N proved useful as a screening test for the diagnosis of sJIA.

Pruebas diagnósticas: Razones de probabilidad / Diagnostic tests: Probability Ratios

La utilidad de una prueba diagnóstica se cuantifica mediante el cálculo de las medidas de probabilidad y las medidas de razones de probabilidad. Las medidas de probabilidad son la sensibilidad, la especificidad, valor predictivo positivo y el valor predictivo negativo. La sensibilidad y la especificidad se usan para escoger la mejor prueba a utilizar, entre varias disponibles; sin embargo, no pueden ser utilizadas para estimar la probabilidad de determinada enfermedad en un paciente en particular. En la práctica clínica es esencial saber cuál es la probabilidad de que un paciente con un resultado positivo en una prueba diagnóstica presente la enfermedad y cuál es la probabilidad de que un paciente con un resultado negativo en una prueba diagnóstica no presente la enfermedad. Los valores predictivos positivos y negativos nos brindan la respuesta a esta cuestión, sin embargo, dependen tanto de la sensibilidad y especificidad, como de la prevalencia de la enfermedad en la muestra del estudio. Las medidas de razones de probabilidad también describen el rendimiento o utilidad de una prueba diagnóstica y poseen dos propiedades importantes: resumen el mismo tipo de información que la sensibilidad y la especificidad, y pueden utilizarse para calcular la probabilidad de la enfermedad después de una prueba positiva o negativa. El propósito de esta publicación fue definir el concepto de razones de probabilidad, exponer sus principales fortalezas y explicar cómo se calculan las razones de probabilidad cuando la prueba de interés expresa sus resultados en forma dicotómica, en más de dos categorías o de forma ordinal

The usefulness of a diagnostic test is quantified by calculating the probability measures and the probability ratio measures. Probability measures are sensitivity, specificity, positive predictive value, and negative predictive value. Sensitivity and specificity are used to choose the best test to use, among several available; however, they cannot be used to estimate the probability of a certain disease in a particular patient. In clinical practice it is essential to know what is the probability that a patient with a positive result in a diagnostic test will present the disease and what is the probability that a patient with a negative result in a diagnostic test will not present the disease. The positive and negative predictive values provide us with the answer to this question, however, it depends both on the sensitivity and specificity, and on the prevalence of the disease in the study sample. Probability ratio measures also describe the performance or usefulness of a diagnostic test and possess two important properties: they summarize the type of information that sensitivity and specificity, and they can be used to calculate the probability of disease after a positive or positive test. negative. The purpose of this publication was to define the concept of probability ratio measures, expose its main strengths, and explain how probability ratio measures are calculated when the test of interest expresses its results dichotomously, in more than two categories or ordinally

Explore functional brain changes in bipolar disorder: A whole brain ALE meta-analysis

ABSTRACT Background: Previous functional magnetic resonance imaging (fMRI) studies showed inconsistent results for comparison between bipolar disorder (BD) and healthy controls (HC). Methods: An anatomic likelihood estimation (ALE) meta-analysis was used to explore the key regions of brain pathology in BD with different current mood states. Results: Depressed BD patients showed reduced regional homogeneity (ReHo) in the left claustrum and the left middle frontal gyrus (MFG), compared to HC. BD patients with mixed mood status showed decreased fractional amplitude of low frequency fluctuations (fALFF) in the right cerebellar tonsil, the bilateral MFG and the right superior frontal gyrus, compared to HC. Additionally, BD patients with mixed mood status showed increased fALFF in the right inferior occipital gyrus, the right culmen and the left lentiform nucleus, compared to HC. BD patients with mixed mood status showed decreased functional connectivity (FC) in the bilateral cerebellar tonsil, compared to HC. Conclusion: In the present study, key regions undergoing functional deficits in BD patients with different current mood states were obtained with the ALE meta-analysis. In addition, deficits in these regions in fMRI studies might work as biomarkers for early diagnosis of BD.

Application of ITO Method in Determination of Special Half-Sibling Relationship / 法医学杂志

OBJECTIVES@#To identify whether the relationship between Zhang A, Zhang B, Zhang C and Zhang X is the half-sibling relationship whose mother is sister (hereinafter referred to as the special half-sibling relationship) or the common first cousin relationship and discuss the application of ITO method in discriminating the special kinship.@*METHODS@#DNA was extracted from blood stain of four identified individuals, PowerPlex® 21 System and AGCU 21+1 STR kit were used to detect autosomal STR genetic markers. Investigator® Argus X-12 QS kit was used to detect the X chromosome STR genetic markers, the special half-sibling index (SHSI) and first cousin index (FCI) and their likelihood ratio (LR) were calculated by ITO method.@*RESULTS@#The LR results of SHSI to FCI, which were calculated based on autosomal STR genotyping and the analysis of X-STR genotyping results suggested that the relationship between Zhang A, Zhang B, Zhang C and Zhang X was inclined to be a special half-sibling relationship.@*CONCLUSIONS@#For the identification of special kinship, it is necessary to comprehensively apply various genetic markers according to the case. After the conclusion that shared alleles cannot be excluded from the analysis, ITO method can be further used to establish discriminant assumptions according to the specific case to obtain objective and reliable identification opinions.

Emotional face processing in patients with social anxiety disorder: an activation likelihood estimation meta-analysis / 中华行为医学与脑科学杂志

Objective:To explore the relevant brain regions of face/non-face processing, and face processing under different emotional valence in patients with social anxiety disorder(SAD).Methods:PubMed, Medline, ScienceDirect, CNKI and other databases were retrieved, and 31 peer-reviewed emotional face studies of SAD patients were obtained (facial and non-facial processing: 13 literatures, 481 subjects, 161 foci; face processing with different emotional titers: 18 literatures, 586 subjects, 331 foci). Cluster-level family-wise error (FWE, P<0.05) based coordinates of Talairach space was adopted. Results:Face processing in SAD patients activated the left amygdala (x=-18, y=-8, z=-12), the right amygdala (x=26, y=0, z=-20), the entorhinal cortex (Brodmann area 28, x=16, y=-8, z=-10) and the medial prefrontal cortex (Brodmann area 10, x=2, y=44, z=-8). In addition, when SAD patients processed negative faces, the left amygdala (x=-26, y=0, z=-16), the right amygdala (x=26, y=0, z=-12), the left medial globus pallidus (x=-20, y=-10, z=-6) and right medial globus pallidus (x=20, y=-10, z=-6) had strong activation, which fear faces activated bilateral amygdala (left: x=-28, y=0, z=-16, right: x=28, y=-2, z=-12) and angry faces activated the medial globus pallidus (x=20, y=-8, z=-6).Conclusion:There are specific neural mechanisms for face processing in patients with SAD.Bilateral amygdala, entorhinal cortex and medial prefrontal cortex are key brain regions for face processing.The amygdala and medial globus pallidus are important neural regions for face processing of negative emotions.