Magnetism and electronic properties of ConMoP (n = 1 ~ 5) cluster: a DFT study.

CONTEXT: Hydrogen has emerged as a promising clean energy carrier, underscoring the imperative need to comprehend its adsorption mechanisms. This study delves into the magnetic and electronic properties of Co-Mo-P clusters, aiming to unveil their catalytic potential in hydrogen production. Employing density functional theory (DFT), we optimized cluster configurations and scrutinized their magnetic behaviors. Our investigation unveiled 16 stable configurations of the ConMoP (n = 1 ~ 5) cluster, predominantly in steric forms. The magnetic attributes were primarily ascribed to the d orbitals of Co metal atoms, with Co3MoP exhibiting exceptional magnetic characteristics. Analysis of density of state diagrams revealed the prevalence of spin-up α-electrons in d orbitals, while spin-down ß-electrons attenuated overall magnetic properties. Localized orbital (LOL) analysis highlighted stable covalent bonds within the clusters, affirming their catalytic potential. Orbital delocalization index (ODI) analysis revealed diverse spatial distribution ranges for orbitals across different configurations, suggesting a progressive attenuation of off-domain properties with increasing cluster size. Furthermore, infrared spectroscopy unveiled distinct vibrational peaks in various configurations, indicative of unique infrared activities. These findings contribute to a nuanced theoretical understanding of Co-Mo-P clusters and pave the path for future research aimed at augmenting their catalytic efficiency in hydrogen production. This study underscores the viability of Co-Mo-P clusters as alternatives to conventional Pt catalysts, offering insights into the design of novel materials for sustainable energy applications. Further research is warranted to explore the behavior of the Co-Mo-P system under diverse reaction conditions, fostering advancements in materials and energy science. METHODS: In this study, we harnessed the ConMoP (n = 1 ~ 5) cluster as a simulation platform for probing the local structure of the material. Our aim was to scrutinize the magnetism, electronic characteristics influenced by the varying metal atoms within these clusters. A systematic exploration involved incrementing the number of metal atoms and expanding the cluster size to elucidate the corresponding property variations. Density functional theory (DFT) calculations were pivotal to our methodology, employing the B3LYP hybrid functional implemented in the Gaussian 16 software package. The ConMoP (n = 1 ~ 5) cluster underwent optimization calculations and vibrational analysis at the def2-tzvp quantization level, yielding optimized configurations with diverse spin multiplet degrees. To comprehensively characterize and visually represent the stability, electronic features, and catalytic attributes of these configurations, we employed a suite of computational tools. Specifically, quantum chemistry software GaussView and wave function analysis software Multiwfn played integral roles. Through the integrated use of these computational tools, we acquired valuable insights into the magnetism, electronic characteristics of the ConMoP (n = 1 ~ 5) cluster, shedding light on their dependency on distinct metal atoms.

Comparative analysis of electronic, magnetic, catalytic properties of clusters (PS4, CrnPS4, AlnPS4, GanPS4, n = 1 ~ 3) based on density functional theory.

CONTEXT: The article presents a comparative study of the electronic, magnetic and catalytic properties of CrPS4, AlPS4, GaPS4 and their expanded structures. It is finally found that: When n = 2, 3, the internal electron mobility of the configurations is stronger than when n = 0,1. When n = 1, the five configurations, except configuration 1Cr(4), are susceptible to both electrophilic and nucleophilic reactions at the same time. The configurations are more prone to nucleophilic reactions when n = 2 and 3, and the reaction sites are mainly located on the metal atoms; the more metal atoms, the more nucleophilic reaction sites. When the M atoms in the configuration are Al and Ga atoms, there is no big difference between the contribution of metal atoms and non-metal atoms to the magnetism in the configuration, while in the configuration containing Cr atoms, the metal atoms contribute more to the magnetism and mainly originate from the d-orbitals, which has better magnetic properties and greater application value. Configuration 2Cr(4) and configuration 1Cr(2) have better catalytic and adsorption activities and are most suitable as catalysts. METHODS: In the article, based on topological principles, density functional theory, B3LYP functional and def2-tzvp basis group and Gaussian16 quantum chemistry software were used to optimise the calculations of the clusters CrPS4, AlPS4, GaPS4 and their expanded configurations, with the most stable structure selected for each cluster, and finally, with the help of Multiwfn program, the required analytical data were obtained by assisting the calculations.

Stability, electronic and catalytic properties of ConMoP(n = 1 ~ 5) clusters: A DFT study.

CONTEXT: The investigation of the stability, electronic properties, and catalytic activity of clusters ConMoP holds significant applications and implications in catalyst design, materials science, energy conversion and storage, and environmental protection. The study aims to delve into the unique features of the clusters ConMoP(n = 1 ~ 5), aiming to drive advancements in these related fields. The results obtained from the analysis revealed the stable configurations of the ten clusters, primarily characterized by steric structures. Furthermore, the energy of the clusters was found to increase continuously during growth, as indicated by calculations of atomic fragmentation energy and atomic binding energy. The researchers conducted an analysis of the Natural Population Analysis(NPA) charge, which revealed that Co atoms acted as electron donors, while P and Mo atoms acted as electron acceptors within the clusters. Additionally, an examination of the electrostatic potential indicated that Co and Mo atoms displayed nucleophilic tendencies, while P atoms exhibited electrophilic characteristics. Moreover, the density of states curves, HOMO and LUMO orbitals, and Kooperman's theorem were applied to the clusters ConMoP(n = 1 ~ 5).Through this study, a deeper understanding of the properties and behavior of clusters ConMoP has been achieved, shedding light on their potential as catalysts. The findings contribute to the existing knowledge of these clusters and provide a basis for further research and exploration in this field. METHODS: In this study, we employed the clusters ConMoP(n = 1 ~ 5) to simulate the local structure of the material, enabling us to investigate the stability, electronic properties, and catalytic properties influenced by the metal atoms. By systematically increasing the number of metal atoms and expanding the cluster size, we explored the variations in these properties. Density functional theory (DFT) calculations were performed using the B3LYP hybrid functional implemented in the Gaussian09 software package. The clusters ConMoP(n = 1 ~ 5) underwent optimization calculations and vibrational analysis at the def2-tzvp quantization level, resulting in optimized configurations with different spin multiplet degrees. For data characterization and graphical representation of the stability, electronic properties, and catalytic properties of the optimized configurations, we utilized a range of computational tools. Specifically, the quantum chemistry software GaussView, wave function analysis software Multiwfn were employed. Through the comprehensive utilization of these computational tools, we gained valuable insights into the stability, electronic properties, and catalytic properties of the clusters ConMoP(n = 1 ~ 5) and their dependence on different metal atoms.

Application of density functional theory to study the electronic structure and magnetic behavior of clusters MnPS3 (M = Fe, Co, Ni; n = 0 ~ 3).

CONTEXT: The article explores and compares the electronic structure and magnetic properties of transition metal phosphate materials, namely FePS3, CoPS3, and NiPS3. RESEARCH FINDINGS: Analysis of the optimized configuration reveals significant insights into the electronic properties of MnPS3 clusters. Electrons within the cluster exhibit a flow from the metal atom M and the non-metal atom P to the non-metal atom S. The S atom serves as the primary site for electrophilic reactions within the cluster, while the metal atom hosts the main site for nucleophilic reactions. Configurations 2a(2), 2b(2), 3a(4), 3b(3), and 3c(2) exhibit enhanced electron mobility and optimal electronic properties. Moreover, the analysis of the magnetic properties of the optimized configurations demonstrates that the magnetic behavior of MnPS3 clusters is influenced by the spin motion of α electrons in the p orbital. Metal atoms make a relatively significant contribution to the magnetic properties of MnPS3 clusters. Configurations 1b(3), 2c(4), and 3a(4) exhibit comparatively higher magnetic properties compared to other configurations of the same size. This study identifies the optimal configuration for the magnetic and electronic properties of transition metal phosphorothioate materials. It also elucidates the trends in magnetic and electronic properties as the number of metal atoms varies, thereby providing valuable theoretical support for the application of these materials in the fields of magnetic materials and electronic devices. METHODS: In this study, the Fe-based transition elements, namely Fe, Co, and Ni, are selected as the metal atoms M. The cluster MPS3 is used to simulate the local structure of the material, allowing for an investigation into the influence of the metal atoms on its electronic and magnetic properties. By increasing the number of metal atoms and expanding the cluster size, the variations in these properties are explored. Density functional theory (DFT) calculations are performed using the B3LYP functional within the Gaussian09 software package. The MnPS3 cluster is subjected to optimal calculations and vibrational analysis at the def2-tzvp quantization level, resulting in optimized configurations with different spin multiplet degrees. Quantum chemistry software GaussView, wave function analysis software Multiwfn, and plotting software Origin are utilized for data characterization and graphical representation of the magnetic and electronic properties of the optimized configurations. Through the employment of these computational tools, valuable insights into the magnetic and electronic properties of the MnPS3 cluster and its dependency on different metal atoms are obtained.

[STAT4 rs7574865 polymorphism is associated with the susceptibility of rheumatoid arthritis in Wuling mountain area].

Objective To investigate the association of single nucleotide polymorphisms (SNPs) of signal transducer and activator of transcription 4 (STAT4) rs7574865 and miRNA146a rs2910164 with rheumatoid arthritis (RA) in Wuling mountain area. Methods 287 RA patients and 305 age-matched healthy controls were included. The rs7574865 and rs2910164 SNPs of RA patients and control subjects were measured by multiplex PCR combined with high throughput sequencing(HI-SNP). The distributions of genotype and allele frequencies in the two groups were analyzed by the Chi-squared test, and also the relationship between these two SNPs and the risk of RA, rheumatoid factor (RF) and anti-cyclic citrullinated peptide (ACCP) antibody were investigated. Results Data showed that the genotype distribution of rs7574865 were significantly different between the cases and controls. The TT genotype and the T allele from rs7574865 were all associated with the risk of RA (OR=2.42, 95%CI: 1.37-4.28; OR=1.43, 95%CI: 1.12-1.82), and dominant and recessive models showed similar results. While, we found miRNA146a rs2910164 has no role in susceptibility to RA, and there was no statistically significant association between the SNPs of rs7574865 and rs2910164 and the level of RF or ACCP antibody. Conclusion STAT4 rs7574865 polymorphism is associated with RA, but not with RF or ACCP antibody levels in Wuling mountain area. In contrast, miRNA146a rs2910164 polymorphism is not correlated with RA.

[Chemical Constituents from Patrinia villosa].

Objective: To investigate the chemical constituents from the ethanol extract of Patrinia villosa. Methods: Various column chromatographic methods including silica gel and Sephadex LH-20 were used for the isolation and purification. Chemical structures were elucidated on the basis of spectroscopic analysis. Results: Six compounds were isolated and identified as 8,9-didehydro-7-hydroxydolichodial-1-dimethyl acetal ( 1), 8,9-didehydro-7-hydroxydolichodial( 2),ursolic acid( 3), 3-O-methylquercetin( 4),luteolin( 5) and kaempferol-3-O-arabinoside( 6). Conclusion: Compound 1 is a new secoiridoid,and compounds 2,4,6 are isolated from the Patrinia genus for the first time.

Effect of Raloxifene on all-cause mortality.

OBJECTIVE: Raloxifene, a selective estrogen receptor modulator, reduces osteoporosis and invasive breast cancer risk but increases risk for venous thromboembolism and fatal stroke in women with or at high risk for coronary heart disease. To assess the risk/benefit of raloxifene as a preventative treatment, we analyzed treatment effects on overall and cause-specific mortality. METHODS: A pooled analysis of mortality data was performed from large clinical trials of raloxifene (60 mg/day) versus placebo, including the Multiple Outcomes of Raloxifene Evaluation/Continuing Outcomes Relevant to Evista studies (7705 postmenopausal osteoporotic women followed for 4 years and a subset of 4011 participants followed for an additional 4 years; 110 deaths) and the Raloxifene Use for the Heart trial (10,101 postmenopausal women with coronary disease or multiple risk factors for coronary disease followed for 5.6 years; 1149 deaths). Cause of death was assessed by blinded adjudicators. Cox proportional hazards regression models compared mortality by treatment assignment in a pooled analysis of trial data from the Multiple Outcomes of Raloxifene Evaluation/Continuing Outcomes Relevant to Evista and Raloxifene Use for the Heart trials. RESULTS: All-cause mortality was 10% lower among women assigned to raloxifene 60 mg/day versus placebo (relative hazard 0.90; 95% confidence interval, 0.80-1.00; P=.05). Lower overall mortality was primarily due to lower rates of noncardiovascular deaths, especially a lower rate of noncardiovascular, noncancer deaths. CONCLUSIONS: All-cause mortality was 10% lower in pooled analyses among older postmenopausal women receiving raloxifene 60 mg/day compared with placebo, due primarily to a reduction in noncardiovascular, noncancer deaths. The mechanism whereby raloxifene might reduce the risk of noncardiovascular death is unclear.

Raloxifene and risk for stroke based on the framingham stroke risk score.

PURPOSE: Raloxifene reduces vertebral fracture and invasive breast cancer risks, but increases fatal strokes in postmenopausal women at increased coronary risk. We assessed whether this risk is concentrated in postmenopausal women already at high stroke risk. METHODS: Raloxifene Use for The Heart (RUTH) enrolled 10,101 postmenopausal women (mean age 67 years) with or at increased coronary heart disease risk; Multiple Outcomes of Raloxifene Evaluation (MORE) enrolled 7705 osteoporotic postmenopausal women (mean age 66 years). A Framingham Stroke Risk Score (FSRS) was calculated for all women with no prior cerebrovascular events (n = 16,858). The validity of the FSRS was assessed in the placebo groups, and then raloxifene-associated stroke risk was analyzed by FSRS subgroups. RESULTS: FSRS predicted an increased stroke risk in the placebo group of both clinical trials. There was no difference in the incidence of nonfatal strokes between the raloxifene and placebo groups in MORE or RUTH, regardless of baseline Framingham stroke risk. In RUTH, women with FSRS <13 showed no increase in raloxifene-associated fatal stroke risk (hazard ratio [HR] 1.08; 95% confidence interval [CI], 0.49-2.37). Those with FSRS >or=13 had a 75% increased risk of raloxifene-associated fatal stroke (HR 1.75; 95% CI, 1.01-3.02; interaction P = .33). In MORE, where 80% of women had a FSRS <13, no increase in fatal (HR 0.57; 95% CI, 0.19-1.68) stroke risk was observed. DISCUSSION: Risk of fatal stroke associated with raloxifene was greater in women at high stroke risk. These results might be useful for identifying postmenopausal women at high risk of first stroke who should avoid raloxifene therapy.

Reduced incidence of invasive breast cancer with raloxifene among women at increased coronary risk.

BACKGROUND: In the Raloxifene Use for The Heart trial, 10 101 postmenopausal women with coronary heart disease (CHD) or multiple CHD risk factors were randomly assigned to 60 mg/d raloxifene or to placebo and followed for a median of 5.6 years. Raloxifene, a selective estrogen receptor modulator, was found to reduce the risk of invasive breast cancer and vertebral fractures but not the risk of cardiovascular events. Here, we provide further details about breast cancer incidence by tumor characteristics, duration of treatment, and subgroup. METHODS: Reported breast cancer was adjudicated by an independent committee based on medical records and pathology reports. The primary analyses used Cox proportional hazards models with time to first breast cancer as the outcome. Subgroup effects were analyzed using similar models with terms for treatment by subgroup. All statistical tests were two-sided. RESULTS: As previously reported, raloxifene reduced the incidence of invasive breast cancer by 44% (hazard ratio [HR] = 0.56; 95% confidence interval [CI] = 0.38 to 0.83; absolute risk reduction = 1.2 invasive breast cancers per 1000 women treated for 1 year). The lower incidence of invasive breast cancer reflected a 55% lower incidence of invasive estrogen receptor (ER)-positive tumors (HR = 0.45; 95% CI = 0.28 to 0.72). However, raloxifene treatment did not reduce the incidence of noninvasive breast cancer or of invasive ER-negative breast cancer. The reduced incidence of invasive breast cancer was similar across subgroups, including those defined by age, body mass index, family history of breast cancer, prior use of postmenopausal hormones, and 5-year estimated risk of invasive breast cancer. CONCLUSION: Raloxifene reduces risk of invasive ER-positive breast cancer regardless of a woman's baseline breast cancer risk but does not reduce risk of noninvasive or ER-negative breast cancers. These results confirm those of the Multiple Outcomes of Raloxifene Evaluation, a previous randomized trial among women with osteoporosis.

Relationship between bone mass, invasive breast cancer incidence and raloxifene therapy in postmenopausal women with low bone mass or osteoporosis.

OBJECTIVE: To evaluate the relationship between bone mass and risk of breast cancer and to determine the effect of raloxifene therapy on breast cancer incidence in women categorized by bone mass into low bone mass and osteoporosis subgroups. DESIGN: In this post hoc analysis, data were analyzed from the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, enrolling postmenopausal women with low bone mass (N = 7705), and the Continuing Outcomes Relevant to Evista (CORE) trial, a follow-up to MORE enrolling 4011 MORE participants. Total follow-up was for up to 8 years. Women with a total hip bone mineral density (BMD) T-score < -1 to > -2.5 or T-score < or = -2.5 (referent, NHANES III database) were classified as having low bone mass or osteoporosis, respectively. Women with a pre-existing vertebral fracture were considered as having osteoporosis irrespective of BMD T-score. Analyses were performed for invasive breast cancers and invasive estrogen-receptor (ER) positive breast cancers. RESULTS: Women with low bone mass (N = 3829) had a twofold higher incidence of invasive ER-positive breast cancer than those with osteoporosis (N = 3836) (HR 2.13, 95% CI 1.12-4.03). The incidence of all invasive breast cancers did not differ significantly between the bone mass groups. The incidences of invasive and invasive ER-positive breast cancers were 65-78% lower in women assigned raloxifene versus placebo in both the low bone mass and osteoporosis groups (p < 0.05). CONCLUSIONS: In this post hoc analysis of postmenopausal women participating in MORE and CORE, bone mass was a predictor of invasive ER-positive breast cancer. Raloxifene treatment reduced the risk of invasive and invasive ER-positive breast cancers in women with low bone mass and those with osteoporosis. Since participants were older postmenopausal women with low bone mass, whether these findings can be generalized to other postmenopausal women is unclear.

Risk factors for breast cancer in older women: the relative contribution of bone mineral density and other established risk factors.

AIM: To determine the contribution of bone mineral density (BMD) to breast cancer risk relative to other established breast cancer risk factors in postmenopausal women with osteoporosis. METHODS: Data for this analysis comprised those collected from women randomized to placebo in the MORE and CORE trials (N = 2,576). Risk factors measured at baseline included age, family history of breast cancer, estradiol level, body mass index, prior hormone therapy, BMD and vertebral fracture status. Cox proportional hazards regression models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Over a total of 13,698 woman-years of follow-up, 65 incident breast cancers occurred. In univariate analyses, older age and family history of breast cancer were the strongest predictors of breast cancer risk, associated with a 2.4- and 2.6-fold increase in breast cancer incidence. A higher estradiol level was associated with a 1.9-fold increase in breast cancer incidence. The association between femoral neck BMD and breast cancer incidence was only significant after adjustment for age (P = 0.03). The final multivariable model included age, family history, estradiol, BMD, and the BMD-estradiol interaction since the effect of BMD on breast cancer varied by estradiol level (interaction P-value, 0.04); in those with a lower estradiol level, a higher BMD was associated with a 2.6-fold increased in breast cancer. CONCLUSION: Overall, BMD is a relatively weak predictor of breast cancer risk in these postmenopausal women with osteoporosis, after taking into consideration age, family history and endogenous estradiol level.

Skeletal effects of raloxifene after 8 years: results from the continuing outcomes relevant to Evista (CORE) study.

UNLABELLED: In the CORE breast cancer trial of 4011 women continuing from MORE, the incidence of nonvertebral fractures at 8 years was similar between placebo and raloxifene 60 mg/day. CORE had limitations for assessing fracture risk. In a subset of 386 women, 7 years of raloxifene treatment significantly increased lumbar spine and femoral neck BMD compared from the baseline of MORE. INTRODUCTION: The multicenter, double-blind Continuing Outcomes Relevant to Evista (CORE) trial assessed the effects of raloxifene on breast cancer for 4 additional years beyond the 4-year Multiple Outcomes of Raloxifene Evaluation (MORE) osteoporosis treatment trial. MATERIALS AND METHODS: In CORE, placebo-treated women from MORE continued with placebo (n = 1286), whereas those previously given raloxifene (60 or 120 mg/day) received raloxifene 60 mg/day (n = 2725). As a secondary endpoint, new nonvertebral fractures were analyzed as time-to-first event in 4011 postmenopausal women at 8 years. A substudy assessed lumbar spine and femoral neck BMD at 7 years, with the primary analysis based on 386 women (127 placebo, 259 raloxifene) who did not take other bone-active agents from the fourth year of MORE and who were > or =80% compliant with study medication in CORE. RESULTS: The risk of at least one new nonvertebral fracture was similar in the placebo (22.9%) and raloxifene (22.8%) groups (hazard ratio [HR], 1.00; Bonferroni-adjusted CI, 0.82, 1.21). The incidence of at least one new nonvertebral fracture at six major sites (clavicle, humerus, wrist, pelvis, hip, lower leg) was 17.5% in both groups. Posthoc Poisson analyses, which account for multiple events, showed no overall effect on nonvertebral fracture risk, and a decreased risk at six major nonvertebral sites in women with prevalent vertebral fractures (HR, 0.78; 95% CI, 0.63, 0.96). At 7 years after MORE randomization, the differences in mean lumbar spine and femoral neck BMD with raloxifene were 1.7% (p = 0.30) and 2.4% (p = 0.045), respectively, from placebo. Compared with MORE baseline, after 7 years, raloxifene treatment significantly increased lumbar spine (4.3% from baseline, 2.2% from placebo) and femoral neck BMD (1.9% from baseline, 3.0% from placebo). BMDs were significantly increased from MORE baseline at all time-points at both sites with raloxifene. CONCLUSION: Raloxifene therapy had no effect on nonvertebral fracture risk after 8 years, although CORE had limitations for fracture risk assessment. BMD increases were maintained after 7 years of raloxifene.

Assay validation for left-censored data.

In laboratory validation studies, it is often important to assess agreement between two assays, based on different techniques. Oftentimes, both assays have lower limits of detection and thus measurements are left censored. For example, in studies of Human Immunodeficiency Virus (HIV), the branched DNA (bDNA) assay was developed to quantify HIV-1 RNA concentrations in plasma. Validation of newer assays, such as the RT-PCR (reverse transcriptase polymerase chain reaction) involves assessing agreement of measurements obtained using the two techniques. Both bDNA and RT-PCR assays have lower limits of detection and thus new statistical methods are needed for assessing agreement between two left-censored variables. In this paper, we present maximum likelihood and generalized estimating equations approaches to evaluate agreement between two assays that are subject to lower limits of detection. The concordance correlation coefficient is used as an agreement index. The methodology is illustrated using HIV RNA assay data collected as part of a long-term HIV cohort study.

Assessing intra, inter and total agreement with replicated readings.

In clinical studies, assessing agreement of multiple readings on the same subject plays an important role in the evaluation of continuous measurement scale. The multiple readings within a subject may be replicated readings by using the same method or/and readings by using several methods (e.g. different technologies or several raters). The traditional agreement data for a given subject often consist of either replicated readings from only one method or multiple readings from several methods where only one reading is taken from each of these methods. In the first case, only intra-method agreement can be evaluated. In the second case, traditional agreement indices such as intra-class correlation (ICC) or concordance correlation coefficient (CCC) is often reported as inter-method agreement. We argue that these indices are in fact measures of total agreement that contains both inter and intra agreement. Only if there are replicated readings from several methods for a given subject, then one can assess intra, inter and total agreement simultaneously. In this paper, we present new inter-method agreement index, inter-CCC, and total agreement index, total-CCC, for agreement data with replicated readings from several methods where the ICCs within methods are used to assess intra-method agreement for each of the several methods. The relationship of the total-CCC with the inter-CCC and the ICCs is investigated. We propose a generalized estimating equations approach for estimation and inference. Simulation studies are conducted to assess the performance of the proposed approach and data from a carotid stenosis screening study is used for illustration.

Overall concordance correlation coefficient for evaluating agreement among multiple observers.

Accurate and precise measurement is an important component of any proper study design. As elaborated by Lin (1989, Biometrics 45, 255-268), the concordance correlation coefficient (CCC) is more appropriate than other indices for measuring agreement when the variable of interest is continuous. However, this agreement index is defined in the context of comparing two fixed observers. In order to use multiple observers in a study involving large numbers of subjects, there is a need to assess agreement among these multiple observers. In this article, we present an overall CCC (OCCC) in terms of the interobserver variability for assessing agreement among multiple fixed observers. The OCCC turns out to be equivalent to the generalized CCC (King and Chinchilli, 2001, Statistics in Medicine 20, 2131-2147; Lin, 1989; Lin, 2000, Biometrics 56, 324-325) when the squared distance function is used. We evaluated the OCCC through generalized estimating equations (Barnhart and Williamson, 2001, Biometrics 57, 931-940) and U-statistics (King and Chinchilli, 2001) for inference. This article offers the following important points. First, it addresses the precision and accuracy indices as components of the OCCC. Second, it clarifies that the OCCC is the weighted average of all pairwise CCCs. Third, it is intuitively defined in terms of interobserver variability. Fourth, the inference approaches of GEE and the U-statistics are compared via simulations for small samples. Fifth, we illustrate the use of the OCCC by two medical examples with the GEE, U-statistics, and bootstrap approaches.