Ultrasound Classification and Preoperative Ultrasound Diagnosis Analysis of Ovarian Ectopic Pregnancy.

This article was published in error while the article requires further revision and has been temporarily removed. 05 August 2024.

Vertasile ferritin nanocages: Applications in detection and bioimaging.

Food safety and human health remain significant concerns in the food industry. Detecting food contaminants and diagnosing diseases are critical aspects. Ferritin, an iron storage protein widely found in nature, offers unique advantages. Its hollow protein nanocage structure, distinct interfaces, hydrophobic or hydrophilic channels, and B-C loop regions recognized by transferrin receptor 1 make ferritin versatile for detecting heavy metals, free radicals, and bioimaging both in vitro and in vivo. This review summarizes ferritin's general characteristics, its specific properties as biosensors, and its applications in food safety and in vivo imaging. It emphasizes not only ferritin's role in detecting heavy metals like mercury and chemical hazards but also its potential in early diagnosing chronic diseases such as tumors, macrophages, and kidney diseases. Further research into ferritin promises advancements in enhancing food safety and improving human health diagnostics.

Rare primary intrapulmonary malignant peripheral nerve sheath tumor showing significant response to sintilimab: A case report and literature review.

Primary pulmonary malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma with a low incidence, poor prognosis and limited treatment options. The present study reported a case of lung MPNST in a 63-year-old male patient without any pulmonary symptoms. Immunohistochemical analysis of the tumor indicated a programmed death-ligand 1 (PD-L1) expression tumor proportion score of 60%. A total of six courses of sintilimab were used in this patient and a remarkable response was achieved. In summary, sintilimab single-agent immunotherapy may be a novel treatment for pulmonary MPNST. When encountering analogous cases in the future, oncologists can test for the expression of PD-L1 in patients to guide the therapy's design.

Efficacy and safety of neoadjuvant immunotherapy plus chemotherapy followed by adjuvant immunotherapy in resectable non-small cell lung cancer: a meta-analysis of phase 3 clinical trials.

Objective: At present, several important trials have been published show that perioperative immunotherapy combined with chemotherapy can improve the prognosis of patients with resectable non-small cell lung cancer, which further optimizes treatment options. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of perioperative immunotherapy combined with chemotherapy in resectable non-small cell lung cancer. Methods: The following databases were searched for relevant studies: PubMed, EMBASE, Cochrane library (updated 12 October 2023). All randomized trials comparing perioperative immunotherapy combined with chemotherapy versus chemotherapy alone in resectable non-small cell lung cancer were eligible for inclusion. Data were analyzed using Review Manager 5.4.1 (Cochrane collaboration software). Primary outcomes and measures included overall survival (OS), event-free survival (EFS), pathological complete response (pCR), major pathological response (MPR), R0 resection rate, rate of underwent surgery and adverse events (AEs). Results: A total of 2912 patients (1453 receiving perioperative immunotherapy plus chemotherapy and 1459 receiving chemotherapy alone) were included in this systematic review and meta-analysis. The result showed that compared with chemotherapy alone, combined therapy significantly improved OS (HR = 0.68;95% CI: 0.56-0.83), EFS (HR = 0.58;95% CI: 0.51-0.65), pCR (OR = 7.53;95% CI: 4.63-12.26), MPR (OR = 5.03;95% CI: 3.40-7.44), R0 resection (OR = 1.58;95% CI: 1.152.18) and rate of underwent surgery (OR = 1.25;95% CI: 1.04-1.49). However, combination therapy was associated with higher risk of severe adverse event (OR = 1.46;95% CI: 1.19-1.78; P=0.0002), grade 3 and higher treatment-related adverse event (TRAE) (OR = 1.25;95% CI: 1.06-1.49; P=0.010), TRAE that led to interruption (OR = 1.90;95% CI: 1.34-2.68; P=0.0003) and immune-related adverse event (OR = 2.78;95% CI: 2.18-3.55; P<0.00001). Significant benefits were observed across most subgroups of EFS and pCR. However, no statistical differences were observed for EFS of never smoked (HR = 0.73;95% CI: 0.51-1.05) and EGFR-mutation positive (HR = 0.35;95% CI: 0.04-3.03). Conclusion: This systematic review and meta-analysis found superior efficacy associated with perioperative immunotherapy plus chemotherapy compared with chemotherapy alone in both tumor regression and prolonged survival in resectable NSCLC, but increased the risk of TRAE, so monitoring for adverse events is warranted. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier (CRD42023476786).

Auxiliary two-filter particle smoothing for one generalized hidden Markov model.

This paper develops two-filter particle smoothing (TFPS) algorithms for the nonlinear fixed-interval smoothing problem of one generalized hidden Markov model (GHMM), where the current observation depends not only on the current state, but also on one-step previous state. Firstly, by Bayesian approach, the two-filter smoothing (TFS) formula for GHMM is established to calculate smoothing densities. In this TFS formula, the backward information prediction density is generally not a density of the state. This results in a difficulty that the normal sequential Monte Carlo (SMC) sampling technique cannot be directly applied to design corresponding TFPS algorithms based on the TFS formula. To solve this difficulty, a generalized TFS formula for GHMM is then proposed by introducing a sequence of artificial densities. By combining this generalized TFS formula, SMC, and the auxiliary variable sampling technique, a basic auxiliary TFPS (ATFPS) algorithm with quadratic computational complexity is proposed, and a simplified ATFPS algorithm with linear computational complexity is further developed. Finally, the effectiveness and superiority of the two proposed ATFPS algorithms for GHMM are verified via simulation examples and real experimental data.

Antifungal efficacy of scorpion derived peptide K1K8 against Candida albicans in vitro and in vivo.

As an alternative class of antimicrobial agents, antimicrobial peptides (AMPs) have gained significant attention. In this study, K1K8, a scorpion AMP derivative, showed effective activity against Candida albicans including clinically resistant strains. K1K8 killed C. albicans cells mainly by damaging the cell membrane and inducing necrosis via an ROS-related pathway. K1K8 could also interact with DNA after damaging the nuclear envelope. Moreover, K1K8 inhibited hyphal development and biofilm formation of C. albicans in a dose-dependent manner. In the mouse skin infection model, K1K8 significantly decreased the counts of C. albicans cells in the infection area. Overall, K1K8 is a potential anti-infective agent against skin infections caused by C. albicans.

Peritoneal Gene Transfection of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand for Tumor Surveillance and Prophylaxis.

Peritoneal metastasis is very common in gastrointestinal, reproductive, and genitourinary tract cancers in late stages or postsurgery, causing poor prognosis, so effective and nontoxic prophylactic strategies against peritoneal metastasis are highly imperative. Herein, we demonstrate the first gene transfection as a nontoxic prophylaxis preventing peritoneal metastasis or operative metastatic dissemination. Lipopolyplexes of TNF-related-apoptosis-inducing-ligand (TRAIL) transfected peritonea and macrophages to express TRAIL for over 15 days. The expressed TRAIL selectively induced tumor cell apoptosis while exempting normal tissue, providing long-term tumor surveillance. Therefore, tumor cells inoculated in the pretransfected peritoneal cavity quickly underwent apoptosis and, thus, barely formed tumor nodules, significantly prolonging the mouse survival time compared with chemotherapy prophylaxis. Furthermore, lipopolyplex transfection showed no sign of toxicity. Therefore, this peritoneal TRAIL-transfection is an effective and safe prophylaxis, preventing peritoneal metastasis.

A preliminary study to quantitatively evaluate the development of maturation degree for fetal lung based on transfer learning deep model from ultrasound images.

PURPOSE: The evaluation of fetal lung maturity is critical for clinical practice since the lung immaturity is an important cause of neonatal morbidity and mortality. For the evaluation of the development of fetal lung maturation degree, our study established a deep model from ultrasound images of four-cardiac-chamber view plane. METHODS: A two-stage transfer learning approach is proposed for the purpose of the study. A specific U-net structure is designed for the applied deep model. In the first stage, the model is to first learn the recognition of fetal lung region in the ultrasound images. It is hypothesized in our study that the development of fetal lung maturation degree is generally proportional to the gestational age. Then, in the second stage, the pretrained deep model is trained to accurately estimate the gestational age from the fetal lung region of ultrasound images. RESULTS: Totally 332 patients were included in our study, while the first 206 patients were used for training and the subsequent 126 patients were used for the independent testing. The testing results of the established deep model have the imprecision as 1.56 ± 2.17 weeks on the gestational age estimation. Its correlation coefficient with the ground truth of gestational age achieves 0.7624 (95% CI 0.6779 to 0.8270, P value < 0.00001). CONCLUSION: The hypothesis that the development of fetal lung maturation degree can be represented by the texture information from ultrasound images has been preliminarily validated. The fetal lung maturation degree can be considered as being represented by the deep model's output denoted by the estimated gestational age.

Dermal exposure to particle-bound polycyclic aromatic hydrocarbons from barbecue fume as impacted by physicochemical conditions.

Inhalation of size-dependent particle-bound polycyclic aromatic hydrocarbons (PAHs) has been extensively studied, whereas dermal absorption has not been adequately investigated. To address this knowledge gap, dermal absorption of size-dependent particle-bound PAHs was characterized through the collection of indoor air and forearm wipe samples in the setting of an indoor barbecue. The mass of size-fractioned PAHs associated with particulate matter was greater in fine particles (<1.8 µm) than in coarse particles (>1.8 µm). Gas-particle distribution of specific PAHs from barbecue fume was ascribed to both adsorption and absorption which would probably be close to equilibrium, while that from background air was dominated by absorption. Forearm-deposited amounts of particulate PAHs suggested that removal of coarse and fine particles could minimize exposure to low and high molecular-weight (MW) PAHs, respectively. Besides, the concentrations of particulate PAHs in forearms wipe were significantly correlated to their dry deposition fluxes with coarse particles, but weakly correlated to those with fine particles. This indicated that particle size would influence dermal absorption efficiency of particle-bound PAHs with fine particles prolonging dermal exposure to PAHs. Overall, higher MW particle-bound PAHs derived from barbecue fume may pose higher risk to human health by dermal absorption than lower MW PAHs.

Nickel-metalated porous organic polymer for Suzuki-Miyaura cross-coupling reaction.

A new Ni(ii)-α-diimine-based porous organic polymer, namely Ni(ii)-α-diimine-POP, was constructed in high yield via the Sonogashira coupling reaction between the metallo-building block of Ni(ii)-α-diimine and 1,3,5-triethynylbenzene. Besides the high thermal and chemical stability, the obtained Ni(ii)-α-diimine-POP can be a highly active reusable heterogeneous catalyst to promote the Suzuki-Miyaura coupling reaction. The obtained results indicate that the Ni(ii)-α-diimine-POP herein is a promising sustainable alternative to the Pd-based catalysts for catalysing the C-C formation in a heterogeneous way.

Porous organic polymer with in situ generated palladium nanoparticles as a phase-transfer catalyst for Sonogashira cross-coupling reaction in water.

A new Pd nanoparticle loaded and imidazolium-ionic liquid decorated organic polymer of Pd@PTC-POP was readily fabricated via a Pd(PPh3)4 catalysed in situ one-pot Suzuki cross-coupling reaction between imidazolium attached dibromobenzene and 1,3,5-tri(4-pinacholatoborolanephenyl)benzene. Besides the high thermal and chemical stability, the obtained Pd@PTC-POP can be used as a highly active and reusable phase-transfer solid catalyst to promote the Sonogashira coupling reaction in water. The obtained results indicate that the Pd@PTC-POP herein could create a versatile family of solid phase transfer catalysts for promoting a broad scope of reactions carried out in water.

Pd(II)-NHDC-Functionalized UiO-67 Type MOF for Catalyzing Heck Cross-Coupling and Intermolecular Benzyne-Benzyne-Alkene Insertion Reactions.

A novel palladium N-heterocyclic bis-carbene dicarboxylate ligand (Pd-NHDC-H2L) was successfully synthesized. In addition, an Pd-NHDC-containing UiO-67 type MOF (UiO-67-Pd-NHDC) was prepared on the basis of a size-matched ligand mixture of biphenyl-4,4'-dicarboxylic acid/Pd-NHDC-H2L (9/1) and ZrCl4 under solvothermal conditions. The obtained UiO-67-Pd-NHC MOF can be a highly heterogeneous catalyst to promote Heck cross-coupling and intermolecular benzyne-benzyne-alkene insertion reactions.

The pollution characteristics of PM2.5 and correlation analysis with meteorological parameters in Xinxiang during the Shanghai Cooperation Organization Prime Ministers' Meeting.

The pollution characteristics of PM2.5 and correlation analysis with meteorological parameters in Xinxiang during the Shanghai Cooperation Organization Prime Ministers' Meeting were investigated. During the whole meeting, nine PM2.5 samples were collected at a suburban site of Xinxiang, and the average concentration of PM2.5 was 122.28 µg m-3. NO3-, NH4+, SO42- accounted for 56.8% of the total water-soluble ions. In addition, with an exception of Cl-, all of water-soluble ions decreased during the meeting. Total concentrations of crustal elements ranged from 6.53 to 185.86 µg m-3, with an average concentration of 52.51 µg m-3, which accounted for 82.5% of total elements. The concentrations of organic carbon and elemental carbon were 7.71 and 1.52 µg m-3, respectively, lower than those before and after the meeting. It is indicated that during the meeting, limiting motor vehicles is to reduce exhaust emissions, delay heating is to reduce the fossil fuel combustion, and other measures are to reduce the concentration of PM2.5. The directly dispersing by mixing layer height increase and the indirectly reducing the formation of secondary aerosol by low relative humidity, and these are the only two key removing mechanisms of PM2.5 in Xinxiang during the meeting.

Clinical impact of improved point-of-care glucose monitoring in neonatal intensive care using Nova StatStrip: Evidence for improved accuracy, better sensitivity, and reduced test utilization.

OBJECTIVES: Studies have demonstrated improved analytical performance of the Nova StatStrip glucose meter, but limited data is available on its clinical performance in critically ill neonates in the neonatal intensive care unit (NICU). DESIGN AND METHODS: A retrospective charge review was conducted on 651 neonates admitted to the NICU over 2 years. Demographics, sample collection information, and clinical details were recorded. Glucose measurements were performed at the bedside using either the Nova StraStrip or LifeScan SureStep Flexx meters as well as corresponding measurements of laboratory venous plasma glucose. Performance was analyzed by receiver operator characteristic (ROC) curves for detecting hypoglycemia and critical glucose levels. RESULTS: Linear regression analysis comparing StatStrip and laboratory venous plasma glucose samples demonstrated significantly tighter agreement (r(2)=0.7994) and accuracy (mean bias=0.13mmol/L) than SureStep (r(2)=0.6845 and mean bias=0.53mmol/L). StatStrip also showed improved sensitivity for detecting critical low glucose values ≤3.0mmol/L (80.9 vs 68.9%, p<0.05). ROC curve analysis further demonstrated excellent performance of StatStrip at this cutoff with an AUC of 0.98. Overall, neonates were also tested significantly less frequently with the StatStrip meter by 24% compared to SureStep. CONCLUSIONS: Implementation of StatStrip led to better agreement with venous plasma glucose, improved detection of critical low glucose results, and more efficient test utilization. This study demonstrates the importance of accurate and sensitive glucose monitoring in the NICU.

Leveraging Big Data to Improve Health Awareness Campaigns: A Novel Evaluation of the Great American Smokeout.

BACKGROUND: Awareness campaigns are ubiquitous, but little is known about their potential effectiveness because traditional evaluations are often unfeasible. For 40 years, the "Great American Smokeout" (GASO) has encouraged media coverage and popular engagement with smoking cessation on the third Thursday of November as the nation's longest running awareness campaign. OBJECTIVE: We proposed a novel evaluation framework for assessing awareness campaigns using the GASO as a case study by observing cessation-related news reports and Twitter postings, and cessation-related help seeking via Google, Wikipedia, and government-sponsored quitlines. METHODS: Time trends (2009-2014) were analyzed using a quasi-experimental design to isolate spikes during the GASO by comparing observed outcomes on the GASO day with the simulated counterfactual had the GASO not occurred. RESULTS: Cessation-related news typically increased by 61% (95% CI 35-87) and tweets by 13% (95% CI -21 to 48) during the GASO compared with what was expected had the GASO not occurred. Cessation-related Google searches increased by 25% (95% CI 10-40), Wikipedia page visits by 22% (95% CI -26 to 67), and quitline calls by 42% (95% CI 19-64). Cessation-related news media positively coincided with cessation tweets, Internet searches, and Wikipedia visits; for example, a 50% increase in news for any year predicted a 28% (95% CI -2 to 59) increase in tweets for the same year. Increases on the day of the GASO rivaled about two-thirds of a typical New Year's Day-the day that is assumed to see the greatest increases in cessation-related activity. In practical terms, there were about 61,000 more instances of help seeking on Google, Wikipedia, or quitlines on GASO each year than would normally be expected. CONCLUSIONS: These findings provide actionable intelligence to improve the GASO and model how to rapidly, cost-effectively, and efficiently evaluate hundreds of awareness campaigns, nearly all for the first time.

Bacillus nitroreducens sp. nov., a humus-reducing bacterium isolated from a compost.

A Gram-staining-positive, facultative anaerobic, motile and rod-shaped bacterium, designated GSS08(T), was isolated from a windrow compost pile and characterized by means of a polyphasic approach. Growth occurred with 0-4 % (w/v) NaCl (optimum 1 %), at pH 6.5-9.5 (optimum pH 7.5) and at 20-45 °C (optimum 37 °C). Anaerobic growth occurred with anthraquinone-2,6-disulphonate, fumarate and NO3 (-) as electron acceptor. The main respiratory quinone was MK-7. The predominant polar lipids were diphosphatidylglycerol and phosphatidylethanolamine. The major fatty acids (>5 %) were iso-C15:0 (43.1 %), anteiso-C15:0 (27.4 %) and iso-C16:0 (8.3 %). The DNA G + C content was 39.6 mol%. The phylogenetic analysis based on 16S rRNA gene sequences revealed that strain GSS08(T) formed a phyletic lineage with the type strain of Bacillus humi DSM 16318(T) with a high sequence similarity of 97.5 %, but it displayed low sequence similarity with other valid species in the genus Bacillus (<96.0 %). The DNA-DNA relatedness between strains GSS08(T) and B. humi DSM 16318(T) was 50.8 %. The results of phenotypic, chemotaxonomic and genotypic analyses clearly indicated that strain GSS08(T) represents a novel species, for which the name Bacillus nitroreducens sp. nov. is proposed. The type strain is GSS08(T) (=KCTC 33699(T) = MCCC 1K01091(T)).

Pediatric reference value distributions and covariate-stratified reference intervals for 29 endocrine and special chemistry biomarkers on the Beckman Coulter Immunoassay Systems: a CALIPER study of healthy community children.

BACKGROUND: The CALIPER program is a national research initiative aimed at closing the gaps in pediatric reference intervals. CALIPER previously reported reference intervals for endocrine and special chemistry markers on Abbott immunoassays. We now report new pediatric reference intervals for immunoassays on the Beckman Coulter Immunoassay Systems and assess platform-specific differences in reference values. METHODS: A total of 711 healthy children and adolescents from birth to <19 years of age were recruited from the community. Serum samples were collected for measurement of 29 biomarkers on the Beckman Coulter Immunoassay Systems. Statistically relevant age and/or gender-based partitions were determined, outliers removed, and reference intervals calculated in accordance with Clinical and Laboratory Standards Institute (CLSI) EP28-A3c guidelines. RESULTS: Complex profiles were observed for all 29 analytes, necessitating unique age and/or sex-specific partitions. Overall, changes in analyte concentrations observed over the course of development were similar to trends previously reported, and are consistent with biochemical and physiological changes that occur during childhood. Marked differences were observed for some assays including progesterone, luteinizing hormone and follicle-stimulating hormone where reference intervals were higher than those reported on Abbott immunoassays and parathyroid hormone where intervals were lower. CONCLUSIONS: This study highlights the importance of determining reference intervals specific for each analytical platform. The CALIPER Pediatric Reference Interval database will enable accurate diagnosis and laboratory assessment of children monitored by Beckman Coulter Immunoassay Systems in health care institutions worldwide. These reference intervals must however be validated by individual labs for the local pediatric population as recommended by CLSI.

Complex reference value distributions and partitioned reference intervals across the pediatric age range for 14 specialized biochemical markers in the CALIPER cohort of healthy community children and adolescents.

BACKGROUND: The CALIPER program has previously reported a comprehensive database of pediatric reference intervals for 63 biochemical and immunochemical markers. Here, covariate-stratified reference intervals were determined for a number of special assays not previously reported. METHODS: A total of 1917 healthy children and adolescents were recruited and serum concentrations of 14 biochemical markers were measured using the Abbott Architect ci4100 system. Age and gender partitions were statistically determined, outliers removed and reference intervals calculated using CSLI C28-A3 guidelines. RESULTS: Many analytes showed dynamic changes in concentration requiring at least 3 age partitions. Unique intervals were required within the first year of life for: pancreatic amylase, C-peptide, ceruloplasmin, insulin, ß-2-microglobulin, cystatin C, dehydroepiandrosterone sulfate (DHEA-S), and α-1-glycoprotein. Cholinesterase, cholinesterase-dibucaine number, and immunoglobulin E required only 2 age partitions and α-1-antitrypsin required only one. Anti-CCP and anti-TPO levels were below the detection limit of the assay. Some analytes including insulin and DHEA-S required additional gender partitions for specific age groups. CONCLUSIONS: Complex profiles were observed for endocrine and special chemistry markers, requiring establishment of age- and gender-specific reference intervals. These updated reference intervals will allow improved laboratory assessment of pediatric patients but should be validated for each analytical platform and local population as recommended by CLSI.

Biochemical marker reference values across pediatric, adult, and geriatric ages: establishment of robust pediatric and adult reference intervals on the basis of the Canadian Health Measures Survey.

BACKGROUND: Biological covariates such as age and sex can markedly influence biochemical marker reference values, but no comprehensive study has examined such changes across pediatric, adult, and geriatric ages. The Canadian Health Measures Survey (CHMS) collected comprehensive nationwide health information and blood samples from children and adults in the household population and, in collaboration with the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER), examined biological changes in biochemical markers from pediatric to geriatric age, establishing a comprehensive reference interval database for routine disease biomarkers. METHODS: The CHMS collected health information, physical measurements, and biosamples (blood and urine) from approximately 12 000 Canadians aged 3-79 years and measured 24 biochemical markers with the Ortho Vitros 5600 FS analyzer or a manual microplate. By use of CLSI C28-A3 guidelines, we determined age- and sex-specific reference intervals, including corresponding 90% CIs, on the basis of specific exclusion criteria. RESULTS: Biochemical marker reference values exhibited dynamic changes from pediatric to geriatric age. Most biochemical markers required some combination of age and/or sex partitioning. Two or more age partitions were required for all analytes except bicarbonate, which remained constant throughout life. Additional sex partitioning was required for most biomarkers, except bicarbonate, total cholesterol, total protein, urine iodine, and potassium. CONCLUSIONS: Understanding the fluctuations in biochemical markers over a wide age range provides important insight into biological processes and facilitates clinical application of biochemical markers to monitor manifestation of various disease states. The CHMS-CALIPER collaboration addresses this important evidence gap and allows the establishment of robust pediatric and adult reference intervals.

Complex reference values for endocrine and special chemistry biomarkers across pediatric, adult, and geriatric ages: establishment of robust pediatric and adult reference intervals on the basis of the Canadian Health Measures Survey.

BACKGROUND: Defining laboratory biomarker reference values in a healthy population and understanding the fluctuations in biomarker concentrations throughout life and between sexes are critical to clinical interpretation of laboratory test results in different disease states. The Canadian Health Measures Survey (CHMS) has collected blood samples and health information from the Canadian household population. In collaboration with the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER), the data have been analyzed to determine reference value distributions and reference intervals for several endocrine and special chemistry biomarkers in pediatric, adult, and geriatric age groups. METHODS: CHMS collected data and blood samples from thousands of community participants aged 3 to 79 years. We used serum samples to measure 13 immunoassay-based special chemistry and endocrine markers. We assessed reference value distributions and, after excluding outliers, calculated age- and sex-specific reference intervals, along with corresponding 90% CIs, according to CLSI C28-A3 guidelines. RESULTS: We observed fluctuations in biomarker reference values across the pediatric, adult, and geriatric age range, with stratification required on the basis of age for all analytes. Additional sex partitions were required for apolipoprotein AI, homocysteine, ferritin, and high sensitivity C-reactive protein. CONCLUSIONS: The unique collaboration between CALIPER and CHMS has enabled, for the first time, a detailed examination of the changes in various immunochemical markers that occur in healthy individuals of different ages. The robust age- and sex-specific reference intervals established in this study provide insight into the complex biological changes that take place throughout development and aging and will contribute to improved clinical test interpretation.