Accurate modeling of temporal correlations in rapidly sampled fMRI time series.

Rapid imaging techniques are increasingly used in functional MRI studies because they allow a greater number of samples to be acquired per unit time, thereby increasing statistical power. However, temporal correlations limit the increase in functional sensitivity and must be accurately accounted for to control the false-positive rate. A common approach to accounting for temporal correlations is to whiten the data prior to estimating fMRI model parameters. Models of white noise plus a first-order autoregressive process have proven sufficient for conventional imaging studies, but more elaborate models are required for rapidly sampled data. Here we show that when the "FAST" model implemented in SPM is used with a well-controlled number of parameters, it can successfully prewhiten 80% of grey matter voxels even with volume repetition times as short as 0.35 s. We further show that the temporal signal-to-noise ratio (tSNR), which has conventionally been used to assess the relative functional sensitivity of competing imaging approaches, can be augmented to account for the temporal correlations in the time series. This amounts to computing the t-score testing for the mean signal. We show in a visual perception task that unlike the tSNR weighted by the number of samples, the t-score measure is directly related to the t-score testing for activation when the temporal correlations are correctly modeled. This score affords a more accurate means of evaluating the functional sensitivity of different data acquisition options.

Comparison of ADVIA Centaur ultra-sensitive and high-sensitive assays for troponin I in serum.

Cardiac troponin I (cTnI) is a standard biomarker for the diagnosis of acute myocardial infarction (AMI). While older, ultra-sensitive cTnI (us-cTnI) assays use the 99th percentile as the reference threshold, newer high-sensitive cTnI (hs-cTnI) assays use the limit of detection or functional sensitivity instead. However, little has been done to systematically compare these two methods. The present study also served as a validation of hs-cTnI in our laboratory. Here, we compared the results obtained from the blood serum obtained from 8810 patients using the us-cTnI and the hs-cTnI assays run in tandem on the ADVIA Centaur XP analyser. We found that in 2279 samples the concentration of cTnI measured with the ultra-sensitive method was below the detection limit, while with the high-sensitive method, only 540 were below the detection limit. We also compared results from these assays with the ultimate diagnosis of a subset of individuals. The analysis of the results below cut-off with the ultra-sensitive method showed that this method would not detect 96 cases related to heart disorder. Overall, the main finding of our research is that hs-cTnI is the preferable option and is able to be deployed effectively in the laboratory setting.

Emerging Patterns of Microbial Functional Traits.

Functional traits are measurable characteristics that affect an organism's fitness under certain environmental conditions. The use of functional traits in microbial ecology holds great promise for improving our ability to develop biogeochemical models and predict ecosystem responses to global changes. Notably, functional traits could be decoupled from taxonomic relatedness, owing to horizontal gene transfer among microorganisms and adaptive evolution. In recent years, our knowledge about microbial functional traits has been substantially enhanced, thereby revealing the multitude of ecological processes in driving community assembly and dynamics. Here, I summarize the emerging patterns of how microbial functional traits respond to changing environments, which considerably differ from better-studied microbial taxonomy. I use niche and neutral theories to explain microbial functional traits. Finally, I highlight future challenges to analyze, elucidate, and utilize functional traits in microbial ecology.

Ecological risk of combined pollution on soil ecosystem functions: Insight from the functional sensitivity and stability.

Assessing the ecological risk of combined pollution, especially from a holistic perspective with the consideration of the overarching functions of soil ecosystem, is crucial and beneficial to the improvement of ecological risk assessment (ERA) framework. In this study, four soils with similar physicochemical properties but contrasting heavy metals contamination levels were selected to explore changes in the integrated functional sensitivity (MSI), resistance (MRS) and resilience (MRL) of soil microbial communities subjected to herbicide siduron, based on which the ecological risk of the accumulation of siduron in the four studied soils were evaluated. The results suggested that the microbial biomass carbon, activity of denitrification enzyme and nitrogenase were indicative of MSI and MRS, and the same three parameters plus soil basal respiration were indicative of MRL. Significant dose-effect relationships between siduron residues in soils and MSI, MRS and MRL under combined pollution were observed. Heavy metal polluted soils showed higher sensitivity and lower resistance to the additional disturbance of herbicide siduron due to the lower microbial biomass, while the resilience of heavy metal polluted soils was much higher due to the pre-adaption to the chemical stresses. The quantifiable indicator microbial functional stability was incorporated in the framework of ERA and the results showed that the accumulation of siduron in the studied soils could exhibit potential harm to the integrated functional stability of soil microbial community. Thus, this work provides insights into the application of integrated function of soil microbial community into the framework of ERA.

How low can you go? Analytical performance of five automated testosterone immunoassays.

BACKGROUND: Testosterone is commonly measured using immunoassays, yet concerns with the accuracy and quality of testing by these methods exist, particularly for low testosterone concentrations. Study objectives were to evaluate selective performance characteristics, including functional sensitivity (FS), of 5 automated immunoassays for total testosterone. METHODS: FS, imprecision, assay interference, limit of blank, linearity, and accuracy were assessed using the Abbott ARCHITECT i2000SR, SIEMENS ADVIA Centaur and IMMULITE 2000, Beckman Coulter DxI 800, and Roche MODULAR E170. Comparisons to an in-house liquid chromatography-tandem mass spectrometry (LC-MS/MS) method were performed using patient samples from men, women, boys, and girls. RESULTS: FS at 20% coefficient of variation (CV) for the ARCHITECT, Centaur, DxI, E170 and IMMULITE assays were 0.14, 1.23, 0.36, 0.77, 3.49 nmol/L, respectively. Total CVs for the 5-day imprecision study were ≤ 9.0% for all methods. All assays met manufacturer's claims for hemolysis, icterus, and lipemia interference and limit of blank. Dilution linearity studies had deviations from the target recoveries ranging from 3.4% (ARCHITECT) to 14.3% (DxI). Using National Institute of Standards and Technology Standard Reference Material 971, recoveries ranged from 79.2-149.2% (DxI, male and female, respectively). When compared to LC-MS/MS, more immunoassays under-recovered in men and women and over-recovered in boys and girls. Slopes ranged from 0.71 (IMMULITE, women) to 1.35 (DxI, boys). The combined average for percent bias was higher in boys (28.0%) than men (11.6%), women (22.8%), and girls (25.7%). CONCLUSIONS: Challenges with accurately measuring testosterone appear to remain for some immunoassays, but not all. While most immunoassays remain optimized for concentrations observed in healthy men, some showed acceptable performance when challenged at lower concentrations.

Novel Nanomonitor ultra-sensitive detection of troponin T.

BACKGROUND: Troponin is the preferred biomarker for diagnosing myocardial infarction. Point of care devices have not matched the sensitivity of laboratory-based methods for measuring troponin. The Nanomonitor is a novel point-of-care device that uses the change in electrical impedance that occurs when a biomarker binds to its antibody, which is then correlated to the concentration of the target biomarker. METHODS: Performance characteristics of the Nanomonitor were evaluated and compared to a standard laboratory-based method. RESULTS: The limit of detection of the Nanomonior for troponin T was 0.0088ng/l. Total imprecission was 2.38% and 0.85% at troponin T concentrations of 73ng/l and 1800ng/l. The functional sensitivity (10% coeffecient of variation) was 0.329ng/l. The linear regression had a slope of 0.996 (95% confidence interval, 0.991, 1.002), r=1.00, and an intercept of 15.88ng/l (95% confidence interval, -68.39ng/l, 100.15ng/l). The mean difference between the assays was -7.54ng/l, determined by Bland-Altman analysis. CONCLUSION: The Nanomonitor preliminary results have favorable performance characteristics for detecting troponin T in patient blood, provide results in 15min, and are portable. More research is needed.

Co-Receptor CD8-Mediated Modulation of T-Cell Receptor Functional Sensitivity and Epitope Recognition Degeneracy.

The interaction between T-cell receptors (TCRs) and peptide epitopes is highly degenerate: a TCR is capable of interacting productively with a wide range of different peptide ligands, involving not only cross-reactivity proper (similar epitopes elicit strong responses), but also polyspecificity (ligands with distinct physicochemical properties are capable of interacting with the TCR). Degeneracy does not gainsay the fact that TCR recognition is fundamentally specific: for the vast majority of ligands, the functional sensitivity of a given TCR is virtually null whereas this TCR has an appreciable functional sensitivity only for a minute fraction of all possible ligands. Degeneracy can be described mathematically as the probability that the functional sensitivity, of a given TCR to a randomly selected ligand, exceeds a set value. Variation of this value generates a statistical distribution that characterizes TCR degeneracy. This distribution can be modeled on the basis of a Gaussian distribution for the TCR/ligand dissociation energy. The kinetics of the TCR and the MHCI molecule can be used to transform this underlying Gaussian distribution into the observed distribution of functional sensitivity values. In the present paper, the model is extended by accounting explicitly for the kinetics of the interaction between the co-receptor and the MHCI molecule. We show that T-cells can modulate the level of degeneracy by varying the density of co-receptors on the cell surface. This could allow for an analog of avidity maturation during incipient T-cell responses.

Assessment of the Precision and Functional Sensitivity of Two Thyroglobulin Assays: Comparison of the Second-Generation Roche Electrochemiluminescent Immunoassay and BRAHAMS Radioimmunoassay

BACKGROUND: Thyroglobulin (Tg) is the primary biochemical marker used to monitor patients with differentiated thyroid cancer (DTC) for residual or recurrent disease after total thyroidectomy, as only normal or well-differentiated malignant thyroid cells produce Tg. Here, we evaluated the precision and functional sensitivity (FS) of a recently developed highly sensitive Tg (hsTg) electrochemiluminescent immunoassay (ECLIA) and compared it to that of the radioimmunoassay (RIA) method using pooled human serum with low levels of Tg. METHODS: For the ECLIA method, the Elecsys Tg II kit (Roche Diagnostics, Germany) was used with an E170 analyzer (Roche Diagnostics). For the RIA method, the Tg-plus-RIA kit (BRAHAMS, Germany) was used with a Cobra Quantum gamma counter (Packard Instrument Company, USA). The precision and limit of detection (LOD) were determined according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. FS was determined using a modification of the CLSI guideline. RESULTS: The total precision of the hsTg ECLIA and RIA methods was 9.6% and 48.2%, respectively. The manufacturer-reported LOD was verified by the hsTg ECLIA (0.04 ng/mL), but not by the RIA method (>0.08 ng/mL). The hsTg ECLIA showed better FS (0.04 ng/mL at a coefficient of variation [CV] of 10%) than the RIA method (0.37 ng/mL at a CV of 20%). CONCLUSIONS: Thus, the hsTg ECLIA performed better than the RIA method in terms of FS, which is extremely important for the early detection of residual or recurrent disease in DTC patients after total thyroidectomy. The excellent performance of the hsTg ECLIA could allow for clinical Tg measurement without thyroid-stimulating hormone stimulation, in contrast to the insufficient performance of the RIA method.

Correctly understand and use analytical sensitivity and limit of detection / 中华检验医学杂志

Limit of detection is one of most important indicators of methodological evaluation.In consideration of the misunderstanding and incorrect differentiating sensitivity and limit of detection by clinical laboratory , equipment and reagent manufacturers and journals of laboratory medicine , this article would show detailed analysis and comparison to figure out the proper use method.

Evaluation of quantitative detection limit and functional sensitivity of prealbumin and their clinical applications analysis / 国际检验医学杂志

Objective To evaluate the limit of blank (LoB),limit of detection (LoD),limit of quantitation(LoQ)and functional sensitivity (FS)of prealbumin (PA)detected by the Roche Modular P automatic biochemical analyzer.Methods According to the EP17A file of the American Clinical and Laboratory Standards Institute (CLSI),saline as the blank sample and a series of low con-centration samples were detected by the Roche Modular P automatic biochemical analyzer for determining LoB,LoD and LoQ.And FS was determined based on the domestic universal method .Results LoB of PA was 16.35 mg/L,LoD was 18.23 mg/L,LoQ was temporarily unable to evaluate and FS was 25.00 mg/L.The report scope and the report mode in clinic were affirmed by combi-ning with the low value of the reportable scope.Conclusion LoD of PA detected by the Roche Modular P automatic biochemical an-alyzer is established,which provides more valuable information for clinical diagnosis and treatment.Conducting the comparison of different evaluation methods determines the advantages and limitation of the practical application of different methods.

O ensaio de tiroglobulina com melhor sensibilidade funcional enquanto os pacientes tomam L-T4 substituirá a tiroglobulina estimulada pelo TSH no seguimento dos pacientes com câncer diferenciado da tiróide? / Will the thyroglobulin assay with lower functional sensitivity whilst the patients are on L-T4 treatment replace the TSH-stimulated thyroglobulin assay in the follow-up of patients with differentiated thyroid cancer?

O autor apresenta evidências recentes da literatura que mostram que ensaios de tiroglobulina sérica (sTg) com maior sensibilidade funcional apresentam a mesma qualidade que a obtenção da sTg estimulada por rhTSH ou hipotiroidismo, no seguimento de pacientes com câncer diferenciado de tiróide (CDT). Desta forma, propõe modificar a prática recomendada pelas diretrizes de sociedades internacionais para o seguimento desses pacientes (desenvolvidas enquanto os ensaios disponíveis apresentavam sensibilidade de 1 ng/mL), substituindo-se a obtenção da sTg estimulada por rhTSH ou hipotiroidismo pelo acompanhamento dos pacientes na vigência da terapia com L-T4 com a medida da sTg desde que se empreguem técnicas com sensibilidade funcional da ordem de 0,1-0,2 ng/mL.

The author reviews the literature on the new assays for serum thyroglobulin (sTg) presenting lower functional sensitivity and demonstrates that its use, whilst the patients are taking L-T4, presents better results than sTg following TSH stimulation in the follow-up of patients with differentiated thyroid carcinoma. Therefore, he suggests a revision on the guidelines for the follow-up of these patients (developed when the available assays present a sensitivity of 1 ng/mL), proposing the use of sTg assays with functional sensitivity of 0.1-0.2 ng/mL with the patients on L-T4 treatment instead of sTg stimulated by TSH.