Pyroelectricity in poled all-organic polar polynorbornene/polydimethylsiloxane-based stretchable electrets.

Pyroelectricity in a recently developed all-organic composite electret with a polar polynorbornene-based filler and polydimethylsiloxane (PDMS) matrix has been studied with the help of thermal and dielectric techniques. Measurement of the pyroelectric p coefficient using a quasi-static periodic temperature variation at RT shows a non-linear dependence with the applied poling field, which is uncharacteristic of amorphous materials. Dielectric relaxation spectroscopy (DRS) and the thermally stimulated depolarization current (TSDC) technique reveal that this behaviour can be attributed to Maxwell-Wagner interface (MWI) polarization that occurs at the filler-matrix interface. These charges released during the onset of dipolar α and ß relaxations of the filler particles contribute majorly to the observed pyroelectricity at RT. The saturation of both MWI TSDC shoulders and spontaneous polarization at higher electric fields correlates with the p coefficient value reaching a plateau at these applied fields. A maximum p coefficient of 0.54 µC m-2 K-1 is calculated for a poling field of 30 V µm-1.

Screening for Primary Aldosteronism by Mass Spectrometry Versus Immunoassay Measurements of Aldosterone: A Prospective Within-Patient Study.

BACKGROUND: Measurements of aldosterone by mass spectrometry are more accurate and less prone to interferences than immunoassay measurements, and may produce a more accurate aldosterone:renin ratio (ARR) when screening for primary aldosteronism (PA). METHODS: Differences in diagnostic performance of the ARR using mass spectrometry vs immunoassay measurements of aldosterone were examined in 710 patients screened for PA. PA was confirmed in 153 patients and excluded in 451 others. Disease classifications were not achieved in 106 patients. Areas under receiver-operating characteristic curves (AUROC) and other measures were used to compare diagnostic performance. RESULTS: Mass spectrometry-based measurements yielded lower plasma aldosterone concentrations than immunoassay measurements. For the ARR based on immunoassay measurements of aldosterone, AUROCs were slightly lower (P = 0.018) than those using mass spectrometry measurements (0.895 vs 0.906). The cutoff for the ARR to reach a sensitivity of 95% was 30 and 21.5 pmol/mU by respective immunoassay and mass spectrometry-based measurements, which corresponded to specificities of 57% for both. With data restricted to patients with unilateral PA, diagnostic sensitivities of 94% with specificities >81% could be achieved at cutoffs of 68 and 52 pmol/mU for respective immunoassay and mass spectrometry measurements. CONCLUSIONS: Mass spectrometry-based measurements of aldosterone for the ARR provide no clear diagnostic advantage over immunoassay-based measurements. Both approaches offer limited diagnostic accuracy for the ARR as a screening test. One solution is to employ the higher cutoffs to triage patients likely to have unilateral PA for further tests and possible adrenalectomy, while using the lower cutoffs to identify others for targeted medical therapy.German Clinical Trials Register ID: DRKS00017084.

Integration of artificial intelligence and plasma steroidomics with laboratory information management systems: application to primary aldosteronism.

OBJECTIVES: Mass spectrometry-based steroidomics combined with machine learning (ML) provides a potentially powerful approach in endocrine diagnostics, but is hampered by limitations in the conveyance of results and interpretations to clinicians. We address this shortcoming by integration of the two technologies with a laboratory information management systems (LIMS) model. METHODS: The approach involves integration of ML algorithm-derived models with commercially available mathematical programming software and a web-based LIMS prototype. To illustrate clinical utility, the process was applied to plasma steroidomics data from 22 patients tested for primary aldosteronism (PA). RESULTS: Once mass spectrometry data are uploaded into the system, automated processes enable generation of interpretations of steroid profiles from ML models. Generated reports include plasma concentrations of steroids in relation to age- and sex-specific reference intervals along with results of ML models and narrative interpretations that cover probabilities of PA. If PA is predicted, reports include probabilities of unilateral disease and mutations of KCNJ5 known to be associated with successful outcomes of adrenalectomy. Preliminary results, with no overlap in probabilities of disease among four patients with and 18 without PA and correct classification of all four patients with unilateral PA including three of four with KCNJ5 mutations, illustrate potential utility of the approach to guide diagnosis and subtyping of patients with PA. CONCLUSIONS: The outlined process for integrating plasma steroidomics data and ML with LIMS may facilitate improved diagnostic-decision-making when based on higher-dimensional data otherwise difficult to interpret. The approach is relevant to other diagnostic applications involving ML.

The Saline Infusion Test for Primary Aldosteronism: Implications of Immunoassay Inaccuracy.

CONTEXT: Diagnosis of primary aldosteronism (PA) for many patients depends on positive results for the saline infusion test (SIT). Plasma aldosterone is often measured by immunoassays, which can return inaccurate results. OBJECTIVE: This study aimed to establish whether differences in aldosterone measurements by immunoassay versus mass spectrometry (MS) might impact confirmatory testing for PA. METHODS: This study, involving 240 patients tested using the SIT at 5 tertiary care centers, assessed discordance between immunoassay and MS-based measurements of plasma aldosterone. RESULTS: Plasma aldosterone measured by Liaison and iSYS immunoassays were respectively 86% and 58% higher than determined by MS. With an immunoassay-based SIT cutoff for aldosterone of 170 pmol/L, 78 and 162 patients had, respectivel, negative and positive results. All former patients had MS-based measurements of aldosterone < 117 pmol/L, below MS-based cutoffs of 162 pmol/L. Among the 162 patients with pathogenic SIT results, MS returned nonpathologic results in 62, including 32 under 117 pmol/L. Repeat measurements by an independent MS method confirmed nonpathogenic results in 53 patients with discordant results. Patients with discordant results showed a higher (P < 0.0001) prevalence of nonlateralized than lateralized adrenal aldosterone production than patients with concordant results (83% vs 28%). Among patients with nonlateralized aldosterone production, 66% had discordant results. Discordance was more prevalent for the Liaison than iSYS immunoassay (32% vs 16%; P = 0.0065) and was eliminated by plasma purification to remove interferents. CONCLUSION: These findings raise concerns about the validity of immunoassay-based diagnosis of PA in over 60% of patients with presumed bilateral disease. We provide a simple solution to minimize immunoassay inaccuracy-associated misdiagnosis of PA.

Replication vesicles are load- and choke-points in the hepatitis C virus lifecycle.

Hepatitis C virus (HCV) infection develops into chronicity in 80% of all patients, characterized by persistent low-level replication. To understand how the virus establishes its tightly controlled intracellular RNA replication cycle, we developed the first detailed mathematical model of the initial dynamic phase of the intracellular HCV RNA replication. We therefore quantitatively measured viral RNA and protein translation upon synchronous delivery of viral genomes to host cells, and thoroughly validated the model using additional, independent experiments. Model analysis was used to predict the efficacy of different classes of inhibitors and identified sensitive substeps of replication that could be targeted by current and future therapeutics. A protective replication compartment proved to be essential for sustained RNA replication, balancing translation versus replication and thus effectively limiting RNA amplification. The model predicts that host factors involved in the formation of this compartment determine cellular permissiveness to HCV replication. In gene expression profiling, we identified several key processes potentially determining cellular HCV replication efficiency.