Add-on testing: stability assessment of 63 biochemical analytes in centrifuged and capped samples stored at 16 °C.

OBJECTIVES: Integration of add-on testing in high-scale automated clinical laboratories constitute a valuable instrument not only for the clinicians and the general patient care, but also for the laboratory itself. Knowledge on sample quality and analytical stability upon storage is necessary to be able to offer add-on testing. The objectives of this study were to examine the analytical stability of 63 biochemical analytes in plasma and urine samples stored at 16 °C. METHODS: Samples were collected by professional laboratory technicians, analyzed at automated analyzers and stored in their primary, capped tube without separator for 10, 12, 16, 20 or 24 h at 16 °C. Stability was assessed by inspecting mean concentration of samples at baseline and examining if (A) mean concentration over time violated limits of bias, or if (B) individual sample concentrations violated limits of total error. RESULTS: The majority of the 63 analytes were stable for up to 24 h of storage. Few of the analytes were only suitable for add-on testing for 4, 6, 10, 12, 16 or 20 h of storage. One analyte, P-lactate dehydrogenase, was not found suitable for add-on testing when stored at 16 °C. CONCLUSIONS: Due to the increasing number of intelligent solutions for high-scale clinical laboratories, add-on testing has come to stay. Loss of stability could not be demonstrated for the majority of analytes after 10, 12, 16, 20 or 24 h of storage. This feature of analytical stability suggests that add-on testing is an acceptable tool for these analytes.

Establishing reference intervals for soluble urokinase plasminogen activator receptor in Northern European adults.

Objectives: Soluble urokinase plasminogen activator receptor (suPAR) may have untapped potential in clinical diagnostics. Previous studies determined reference intervals using an enzyme-linked immunoassay, but there is a need for reference intervals using a faster assay if the analysis is to be used in emergency medicine. The current study aims to determine reference intervals for suPAR using a fully automated particle-enhanced turbidimetric immunoassay (PETIA) according to the Clinical and Laboratory Standards Institute guideline A28-A3c. Design and methods: Blood samples were prospectively collected from Danish blood donors. Plasma suPAR was analyzed on the cobas 8000 module c502 in an open channel using a PETIA. Sex-partitioned reference intervals were determined using a parametric quantile approach. Results: The study included 241 participants-123 females and 118 males. The common reference interval for suPAR was 1.56-4.11 ng/mL (95% confidence intervals (CI) for the lower and upper limits were 1.56-1.63 and 3.81-4.47, respectively). The reference interval for females was 1.59-4.65 ng/mL (95% CIs 1.48-1.70 and 4.09-5.48, respectively) and for males, 1.56-3.59 ng/mL (95% CIs 1.47-1.65 and 3.31-3.93, respectively). Conclusions: Our results support using sex-partitioned reference intervals for suPAR and provide a basis for future studies using the PETIA method.

Unbiased and efficient estimation of causal treatment effects in crossover trials.

We introduce causal inference reasoning to crossover trials, with a focus on thorough QT (TQT) studies. For such trials, we propose different sets of assumptions and consider their impact on the modeling strategy and estimation procedure. We show that unbiased estimates of a causal treatment effect are obtained by a g-computation approach in combination with weighted least squares predictions from a working regression model. Only a few natural requirements on the working regression and weighting matrix are needed for the result to hold. It follows that a large class of Gaussian linear mixed working models lead to unbiased estimates of a causal treatment effect, even if they do not capture the true data-generating mechanism. We compare a range of working regression models in a simulation study where data are simulated from a complex data-generating mechanism with input parameters estimated on a real TQT data set. In this setting, we find that for all practical purposes working models adjusting for baseline QTc measurements have comparable performance. Specifically, this is observed for working models that are by default too simplistic to capture the true data-generating mechanism. Crossover trials and particularly TQT studies can be analyzed efficiently using simple working regression models without biasing the estimates for the causal parameters of interest.

Establishing Sex-Dependent Reference Intervals for KL-6 in Danish Adults.

Krebs von den Lungen-6 (KL-6) is a promising biomarker for the diagnosis and prognosis of interstitial lung disease. However, reference intervals in Northern Europeans remain to be established using a latex-particle-enhanced turbidimetric immunoassay. The participants were Danish blood donors subjected to strict health requirements. Analyses were performed using the Nanopia KL-6 reagent on the cobas 8000 module c502. Sex-partitioned reference intervals were determined using a parametric quantile approach according to the Clinical and Laboratory Standards Institute guideline EP28-A3c. The study included 240 participants-121 females and 119 males. The common reference interval was 59.4-398.5 U/mL (95% confidence intervals (CI) for the lower and upper limits were 47.3-71.9 and 369.5-430.1, respectively). For females, the reference interval was 56.8-324.0 U/mL (95% CIs for the lower and upper limits were 36.1-77.6 and 303.3-344.7, respectively). For males, the reference interval was 51.5-448.7 U/mL (95% CIs for the lower and upper limits were 32.8-71.2 and 397.3-508.1, respectively). These results emphasize the importance of sex partitioning when evaluating KL-6 reference intervals. The reference intervals increase the clinical applicability of the KL-6 biomarker and provide a basis for future scientific studies of its utility in patient management.

Faecal haemoglobin concentration predicts all-cause mortality.

BACKGROUND: Population-based screening for colorectal cancer by a faecal immunochemical test (FIT) is recommended by the European Union. Detectable faecal haemoglobin can indicate colorectal neoplasia as well as other conditions. A positive FIT predicts an increased risk of death from colorectal cancer but might also predict an increased risk of all-cause mortality. METHODS: A cohort of screening participants was followed using the Danish National Register of Causes of Death. Data were retrieved from the Danish Colorectal Cancer Screening Database supplemented with FIT concentrations. Colorectal cancer specific and all-cause mortality were compared between FIT concentration groups using multivariate cox proportional hazards regression models. FINDINGS: In 444,910 Danes invited for the screening program, 25,234 (5·7%) died during a mean follow-up of 56·5 months. Colorectal cancer caused 1120 deaths. The risk of colorectal cancer death increased with the increasing FIT concentration. The hazard ratios ranged from 2·6 to 25·9 compared to individuals with FIT concentrations <4 µg hb/g faeces. Causes other than colorectal cancer caused 24,114 deaths. The risk of all-cause death increased with the increasing FIT concentration, with the hazard ratios ranging from 1·6 to 5·3 compared to individuals with FIT concentrations <4 µg hb/g faeces. INTERPRETATION: The risk of colorectal cancer mortality increased with the increasing FIT concentrations even for FIT concentrations considered negative in all European screening programs. The risk of all-cause mortality was also increased for individuals with detectable faecal blood. For colorectal cancer specific mortality and all-cause mortality, the risk was increased at the FIT concentrations as low as 4-9 µg hb/g faeces. FUNDING: The study was funded by the Odense University Hospital grants A3610 and A2359.

Motivational predictors of children's involvement in out-of-school activities: An application of a football program.

The "11 for Health in Denmark" in-school educational football program has shown to have numerous positive physiological and psychological effects in 10- to 12-year-old schoolchildren. A key part of the successful application of the program, however, has not yet been examined, namely the motivational processes underlying participation and behavioral changes. This study examined such motivational processes (i.e., autonomous motivation, beliefs, and intentions) using the trans-contextual model (TCM) and investigated if the 11 for Health in Denmark program increased intentions to participate in physical activity (PA) outside of school in 10- to 12-year-old schoolchildren. Using a web-based questionnaire, Danish-speaking schoolchildren (N = 276 [boys, 50.4%]; Mage  = 10.44, SD = 0.35) from three schools and seven classes completed TCM-based questionnaires at three time-points (weeks 0, 1, and 5) while participating in the 11 for Health in Denmark program. Single-indicator structural equation modeling was performed to examine goodness-of-fit and parameter estimates. A path analysis using maximum likelihood estimation was used to test the direct and indirect effects of the TCM model. The results partly supported a mediation sequence, as we found significant direct effects in eight of 13 motivational variables (ß = -0.25-0.83, p < 0.05), indirect effects in one of nine variables (ß = 0.15, p < 0.01), but no effects with regard to PA behavior. Findings provide evidence for a motivational link between Danish-speaking schoolchildren's autonomous and controlled motivation from in school to out of school, and may inform future interventions promoting motivation and participation in out of school PA.

Scalable Synthetic Route to PDMS Ring Polymers in High Yields from Commercially Available Materials Using the Piers-Rubinsztajn Reaction.

While cyclic polymers have intrigued researchers for their novel set of architecture-driven rheological interactions, the possibility of incorporating them in topological systems has been limited by the availability of large ring polymers. Thus, the need for scalable methods to produce ring polymers has become apparent. Here, a facile method to prepare polysiloxane ring polymers by means of Piers-Rubinsztajn chemistry is presented. The one-pot nature and commercial availability of reagents additionally confirm the applicability of the method for large-scale production. Furthermore, a highly efficient yet simple purification method was developed for the isolation of pure ring polymers without linear side products.

Using fecal immunochemical test values below conventional cut-off to individualize colorectal cancer screening.

Background and study aims Of the participants in the Danish screening program, 89.9 % to 92.5 % have fecal immunochemical test (FIT) values < 10 µg/g feces (equivalent to 50 ng hemoglobin/mL buffer). This study aimed to investigate the risk of interval colorectal cancer (CRC) in this group before the next biennial screening round. Patients and methods This cohort study included all citizens from the region of Southern Denmark who participated in the Danish bowel screening program from 2014 trough 2016 and had a FIT value < 10 µg/g feces. Individuals receiving a CRC diagnosis were identified through the national CRC registry, with a follow up of 2 years corresponding to the current screening interval. We also examined the 3-year CRC incidence. Hazard ratios (HRs) were estimated using univariate and multivariate Cox proportional hazard regression models. Results Data from 185,654 citizens presenting with a FIT value < 10 µg/g feces were eligible for analysis. Overall, interval CRC incidence was 0.07 % within 2 years with HRs of 4.16 (95 % confidence interval [CI] 2.67;6.48) and 5.8 (95 % CI 3.34;10.05) for FIT values of 4 to 6.9 µg/g feces and 7 to 9.9 µg/g feces, respectively, compared to those having a FIT value below the limit of quantification of 4 µg/g feces. After 3 years, the overall CRC incidence increased to 0.14 %; however, this was not significant. Conclusions This study demonstrates a positive correlation between FIT value and risk of interval cancer even for very low values. It further suggests that an increase in the screening interval could be reasonable in the low FIT categories.

Higher free thyroxine associated with PFAS exposure in first trimester. The Odense Child Cohort.

BACKGROUND: Perfluoroalkyl substances (PFAS) are endocrine disrupting chemicals with elimination half-lives ranging from four to eight years. Experimental studies found PFAS able to interfere with thyroid hormone-binding proteins. During the first 20 weeks of gestation (GW), the fetus is reliant on placental transfer of maternal thyroid hormones, mainly free thyroxine (FT4). However, previous studies investigating associations between exposure to PFAS and thyroid hormone status mainly focused on blood samples from late pregnancy or umbilical cord with mixed findings. OBJECTIVES: To investigate associations between serum-PFAS concentrations and thyroid hormone status in early pregnancy as reflected by FT4 and thyroid-stimulating hormone (TSH). METHODS: In the Odense Child Cohort, a single-center study, we measured maternal pregnancy serum concentrations of five PFAS: perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA); and FT4 and TSH in 1048 pregnant women at median GW 12 (25th, 75th percentile: 10, 15). Multivariate linear regression models were performed to estimate associations between PFAS exposure and thyroid hormone status. RESULTS: A doubling in PFOS, PFOA, and PFNA concentrations was associated with an increment in FT4 concentration by 1.85% (95% CI: 0.66%, 3.05%), 1.29% (95% CI: 0.21%, 2.39%), and 1.70% (95% CI: 0.48%, 2.94%), respectively, in adjusted analyses. A statistically significant dose-response relationship was observed across exposure quartiles for PFOS, PFOA, and PFNA in the association with FT4. No association was found between concentrations of PFAS and TSH in adjusted analyses. CONCLUSION: Exposure to PFOS, PFOA, and PFNA was associated with higher FT4 concentrations in women during early pregnancy. The potential clinical implications of these findings remain to be clarified.

Evaluation of the point-of-care devices KetoSureTM and StatStrip Express® blood ketone tests using ß-hydroxybutyrate spiked samples.

Measurement of ß-hydroxybutyrate (BHB) in blood is used clinically as a measure of ketosis when diabetic ketoacidosis is expected. With the introduction of point-of-care testing (POCT) for blood-BHB, nonproductive time is reduced to a minimum in a potential critical situation; however, studies have observed inferior quality of POCT-BHB. Recently, the POCT device KetoSure (Roche) has been introduced to the clinic. In this study, we evaluated the imprecision and linearity of KetoSure and compared this to the established StatStrip Express (Nova Biomedical) based on spiked full blood samples. We found comparable imprecision for KetoSure and StatStrip Express. However, linearity was only observed in the lower part of the measuring range for both devices. In a method comparison, higher values of BHB were measured by KetoSure than by an enzymatic endpoint spectrophotometric reference method (mean bias: 21% (95% confidence interval (CI): 4%-37%)). Conversely, StatStrip Express returned lower values of BHB (mean bias: -16% (95% CI: -38%-7%), while the widely applied POCT device FreeStyle Precision Neo (Abbott) returned values equivalent with the reference method (mean bias: 5% (95% CI: -14%-24%). In samples with concentrations of BHB above the measuring range, the POCT devices could be provoked to return falsely low results. In conclusion, the quality of KetoSure is in line with other established POCT devices; however, the KetoSure measures higher concentrations than other POCT devices. As, linearity only was observed in the lower part of the measuring range and as falsely low measures could be provoked, we advise users to interpret results with precaution.

One reaction to make highly stretchable or extremely soft silicone elastomers from easily available materials.

Highly stretchable, soft silicone elastomers are of great interest for the fabrication of stretchable, soft devices. However, there is a lack of available chemistries capable of efficiently preparing silicone elastomers with superior stretchability and softness. Here we show an easy curing reaction to prepare silicone elastomers, in which a platinum-catalyzed reaction of telechelic/multi-hydrosilane (Si-H) functional polydimethylsiloxane (PDMS) in the presence of oxygen and water leads to slow crosslinking. This curing chemistry allows versatile tailoring of elastomer properties, which exceed their intrinsic limitations. Specifically, both highly stretchable silicone elastomers (maximum strain of 2800%) and extremely soft silicone elastomers (lowest shear modulus of 1.2 kPa) are prepared by creating highly entangled elastomers and bottle-brush elastomers from commercial precursor polymers, respectively.

Sampling in the case-time-control design among drug users when outcome prevents further treatment.

PURPOSE: The objective of this article is to advocate a new way of sampling controls in the case-time-control design in a cohort of drug users when the studied outcome prevents further treatment. METHODS: Mathematically we demonstrate how a standard sampling of controls, where controls are sampled among all subjects without an event at end-of-study, leads to a biased effect estimate. We propose to add the requirement that controls initiate treatment before the calendar time of event of their matched case to circumvent this. The standard and proposed sampling methods are compared in a simulation study and in an empirical data example examining the effect of nonsteroidal anti-inflammatory drug usage on the risk of upper gastrointestinal bleeding. RESULTS: When the controls are sampled the standard way, the case-time-control design confers a bias because cases and controls have a different time-trend of exposure. The bias has been upwards in all the scenarios we have investigated. The requirement we add to be a potential control ensures that cases and controls have the same time-trend of exposure when treatment and outcome are independent. The simulation study confirms that the proposed sampling method removes the bias between treatment and outcome. The proposed sampling method lowered the odds-ratio estimate from 3.72 to 3.26 in the data example. CONCLUSION: The proposed sampling method makes it possible to use the case-time-control design in a cohort of subjects with registered use of a drug when outcome prevents further treatment.

Highly Stretchable Silicone Elastomer Applied in Soft Actuators.

In this work, a highly stretchable silicone elastomer is incorporated into dielectric elastomer actuators (DEAs) in order to decrease operation voltages by applying high prestretches. Results show that the fabricated DEAs (5 mm diameter circle active region) can be actuated to a lateral strain of 30% at 4.3 kV for a 122 µm thick prestretched film, and to a lateral strain of 2.5% at only 250 V for a 6.9 µm thick prestretched film. Due to the significant viscous component of the silicone elastomer, the DEAs respond more slowly (2-14 s to reach 90% of full strain) and show greater strain changes over time compared to conventional silicone-based DEAs. While this inherent viscosity is not universally favorable, it can be advantageous in applications where actuator damping is desirable. The studied DEAs' mean lifetimes under DC actuation range significantly-from 0.9 h to more than 123.0 h-depending mainly on initial electrical fields (17.8-36.3 V µm-1 ). For instance, DEAs with a 150 µm initial thickness and a prestretch ratio of 3 show 1.4-2.6% lateral strains for the mean lifetime (123.0 h) at only 300 V. Given the strains achieved at low voltage, such DEAs show promise for applications that do not require fast response speeds.

Colon capsule endoscopy in colorectal cancer screening: Interim analyses of randomized controlled trial CareForColon2015.

Background and study aims The Danish CareForColon2015 trial, launched in 2020 as part of the Danish Colorectal Cancer Screening program, is the largest randomized controlled trial to date on colon capsule endoscopy (CCE). This paper presents the interim analysis with the objective of ensuring the safety of patients in the intervention group and evaluating the clinical performance of the trial's predefined clinical parameters. Patients and methods We evaluated the initial 234 CCEs according to quality, safety, and completion. The participation rates and preference distribution of all individuals invited were analyzed and sample size calculations were adjusted. Results Fecal immunochemical test and diagnostic participation rates were 62.1 % and 91.1 %, respectively. The completion rate for CCEs was 67.9 % and the rate of conclusive investigations was 80.3 %. The polyp detection rate (PDR) was high (73.5 %), only two (0.85 %) technical failures in 234 videos were observed, and six suspected cancers were identified (2.6 %). No major adverse events were recorded. The required number of invitations had been underestimated due to inaccurate assumptions in sample size calculations. Conclusions The trial was efficient and safe in terms of CCE quality and time to diagnostic investigation. Participation rates and PDRs were high. The proportion of suspected cancers was lower than expected and will be followed. The completion rate for CCEs was acceptable but lower than expected and the CCE procedure was reviewed for potential improvements and Resolor was added to the regime. The number of invitations for the intervention group of the trial has been adjusted from 62,107 to 185,153.

The Soluble Urokinase-Type Plasminogen Activator Receptor as a Biomarker for Survival and Early Treatment Effect in Metastatic Colorectal Cancer.

The soluble urokinase-type plasminogen activator receptor (suPAR) is prognostic for overall survival (OS) in colorectal cancer (CRC). Our study explored the association between baseline suPAR and OS and progression-free survival (PFS) in metastatic CRC (mCRC). It is also the first study to explore the association between the initial change in suPAR level and OS, PFS and the first CT response evaluation. The study included 132 patients with mCRC treated with chemotherapy (FOLFIRI) with or without an EGFR-inhibitor. Blood samples were drawn before the first treatment cycle and in between the first and second treatment cycle. suPAR levels were determined using an ELISA assay. Using the Kaplan-Meyer method, we demonstrated a significantly shorter OS for patients with suPAR levels above the median (HR = 1.79, 95%CI = 1.10-2.92, p = 0.01). We also showed association between plasma suPAR level, gender and performance status (PS). However, we could not show any association with PFS, and analysis on the change in suPAR level provided no significant results. The results showing association between baseline suPAR and OS are in line with previous findings.

Quantifying SARS-CoV-2 nucleocapsid antigen in oropharyngeal swabs using single molecule array technology.

This study aimed to develop a highly sensitive SARS-CoV-2 nucleocapsid antigen assay using the single molecule array (Simoa) technology and compare it with real time RT-PCR as used in routine clinical practice with the ambition to achieve a comparative technical and clinical sensitivity. Samples were available from 148 SARS-CoV-2 real time RT-PCR positive and 73 SARS-CoV-2 real time RT-PCR negative oropharyngeal swabs. For determination of technical sensitivity SARS-CoV-2 virus culture material was used. The samples were treated with lysis buffer and analyzed using both an in-house and a pre-commercial SARS-CoV-2 nucleocapsid antigen assay on Simoa. Both nucleocapsid antigen assays have a technical sensitivity corresponding to around 100 SARS-CoV-2 RNA molecules/mL. Using a cut-off at 0.1 pg/mL the pre-commercial SARS-CoV-2 nucleocapsid antigen assay had a sensitivity of 96% (95% CI 91.4-98.5%) and specificity of 100% (95% CI 95.1-100%). In comparison the in-house nucleocapsid antigen assay had sensitivity of 95% (95% CI 89.3-98.1%) and a specificity of 100% (95% CI 95.1-100%) using a cut-off at 0.01 pg/mL. The two SARS-CoV-2 nucleocapsid antigen assays correlated with r = 0.91 (P < 0.0001). The in-house and the pre-commercial SARS-CoV-2 nucleocapsid antigen assay demonstrated technical and clinical sensitivity comparable to real-time RT-PCR methods for identifying SARS-CoV-2 infected patients and thus can be used clinically as well as serve as a reference method for antigen Point of Care Testing.

A Synthetic Overview of Preparation Protocols of Nonmetallic, Contact-Active Antimicrobial Quaternary Surfaces on Polymer Substrates.

Antibacterial surfaces have been researched for more than 30 years and remain highly desirable. In particular, there is an interest in providing antimicrobial properties to commodity plastics, because these, in their native state, are excellent substrates for pathogens to adhere and proliferate on. Therefore, efficient strategies for converting surfaces of commodity plastics into contact-active antimicrobial surfaces are of significant interest. Many systems have been prepared and tested for their efficacy. Here, the synthetic approaches to such active surfaces are reviewed, with the restriction to only include systems with tested antibacterial properties. The review focuses on the synthetic approach to surface functionalization of the most common materials used and tested for biomedical applications, which effectively has limited the study to quaternary materials. For future developments in the field, it is evident that there is a need for development of simple methods that permit scalable production of active surfaces. Furthermore, in terms of efficacy, there is an outstanding concern of a lack of universal antimicrobial action as well as rapid deactivation of the antibacterial effect through surface fouling.

Daily monitoring of viral load measured as SARS-CoV-2 antigen and RNA in blood, IL-6, CRP and complement C3d predicts outcome in patients hospitalized with COVID-19.

OBJECTIVES: We hypothesized that the amount of antigen produced in the body during a COVID-19 infection might differ between patients, and that maximum concentrations would predict the degree of both inflammation and outcome for patients. METHODS: Eighty-four hospitalized and SARS-CoV-2 PCR swab-positive patients, were followed with blood sampling every day until discharge or death. A total of 444 serial EDTA plasma samples were analyzed for a range of biomarkers: SARS-CoV-2 nuclear antigen and RNA concentration, complement activation as well as several inflammatory markers, and KL-6 as a lung marker. The patients were divided into outcome groups depending on need of respiratory support and death/survival. RESULTS: Circulating SARS-CoV-2 nuclear antigen levels were above the detection limit in blood in 65 out of 84 COVID-19 PCR swab-positive patients on day one of hospitalization, as was viral RNA in plasma in 30 out of 84. In all patients, complete antigen clearance was observed within 24 days. There were definite statistically significant differences between the groups depending on their biomarkers, showing that the concentrations of virus RNA and antigen were correlated to the inflammatory biomarker levels, respiratory treatment and death. CONCLUSIONS: Viral antigen is cleared in parallel with the virus RNA levels. The levels of antigens and SARS-CoV-2 RNA in the blood correlates with the level of IL-6, inflammation, respiratory failure and death. We propose that the antigens levels together with RNA in blood can be used to predict the severity of disease, outcome, and the clearance of the virus from the body.

Free thyroxine in early pregnancy is an independent negative predictor of 3rd trimester HbA1c. Odense child cohort.

BACKGROUND: Lower thyroid function outside pregnancy is associated with an increased risk of type 2 diabetes mellitus. The relationship between thyroid function in early pregnancy and glucose status in 3rd trimester has not been investigated. AIMS: To study the association between 1st trimester thyroid function and 3rd trimester glucose status. DESIGN: In the prospective study Odense Child Cohort (OCC), 1,041 women had 1st trimester blood samples analysed for thyroid-stimulating hormone (TSH), free T4 (FT4), thyroid peroxidase antibody and HbA1c. Third trimester (week 28) fasting blood samples included plasma glucose, insulin and HbA1c. Oral glucose tolerance test (OGTT, 75 g glucose) was performed in 509 women. First trimester FT4 was dichotomized >vs. ≤ the 25th percentile (25p = 12.9 pmol/L). Homeostatic model assessment-insulin resistance (HOMA)-IR and HOMA-ß were calculated. RESULTS: Women with FT4 ≤25p had significantly higher HbA1c in 1st and 3rd trimesters and higher 3rd trimester fasting glucose, insulin, HOMA-IR and HOMA-ß compared to women with FT4 >25p. In multiple regression analyses, FT4 was an independent negative predictor of 3rd trimester HbA1c. FT4 levels in 3rd and 4th quartiles (high-normal FT4 levels) showed closest inverse associations with HbA1c (p-trend <.001). TSH was not associated with 3rd trimester HbA1c. CONCLUSION: Women with lower levels of FT4 in early pregnancy had higher HbA1c in 3rd trimester and FT4 was an independent negative predictor of 3rd trimester HbA1c.

Novel polyrotaxane cross-linkers as a versatile platform for slide-ring silicone.

Slide-ring elastomers have garnered a lot of interest for their potential use in dielectric elastomer actuators due to their intrinsically soft nature and high elasticity. However, the use of sliding cross-linkers has been constrained by their low miscibility with commonly used elastomer precursors and the specialized curing chemistries that are necessary for incorporating them into networks. Here, we have presented a method to produce vinyl functional polyrotaxane cross-linkers that are compatible with polysiloxanes and can be processed by industrially scalable methods. The sliding silicone films that were fabricated with these novel cross-linkers were highly extensible (>350%) and did not exhibit strain hardening even at high elongation. The composite films also retained the favorable dielectric properties of silicone elastomers such as the characteristic low dielectric loss. The modified polyrotaxanes present a robust platform for producing a new class of sliding silicone elastomers with well-defined networks structures.