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Both multifocal motor neuropathy (MMN) and chronic inflammatory demyelinating polyneuropathy (CIDP) are chronic progressive immune-mediated peripheral neuropathies without sensory loss. We aimed to explore the different features of ultrasonographic and electrophysiological changes among MMN, motor CIDP and typical CIDP patients.
Methods:
Nerve ultrasonographic studies were performed in 19 patients with MMN, 15 patients with motor CIDP and 117 patients with typical CIDP. Cross-sectional areas (CSAs) were measured on the bilateral median and ulnar nerves and brachial plexus. Nerve conduction studies (NCSs) were performed on the median and ulnar nerves.
Results:
In patients with MMN and typical CIDP, the percentage enlargement in the brachial plexus (MMN 45.7%, typical CIDP 78%) was similar to that in the arm (MMN 42.9%, typical CIDP 76.8%) and forearm (MMN 42.9%, typical CIDP 79.4%). However, in patients with motor CIDP, the percentage enlargement in the brachial plexus (74.1%) was more pronounced than in the arm (65.5%) and forearm (58.6%). The CMAPerb/CMAPaxilla in MMN was significantly higher than in motor CIDP (median nerve, 0.82 ± 0.28 for MMN and 0.60 ± 0.37 for motor CIDP, P = 0.017). The CSA decreased in the order of typical CIDP, motor predominant CIDP (MPred-CIDP), pure motor CIDP (PM-CIDP) and MMN. The motor nerve conduction velocity increased in the order of typical CIDP, MPred-CIDP, PM-CIDP and MMN. A total of 3/6 PM-CIDP and 3/3 MPred-CIDP patients responded to steroid treatment.
Conclusion:
Treatment response, nerve ultrasonography and NCS in MMN, PM-CIDP, MPred-CIDP and typical CIDP constitute a spectrum.
With the widespread use of high-fat diets (HFD) in aquaculture, the adverse effects of HFD on farmed fish are becoming increasingly apparent. Creatine has shown potential as a green feed additive in farmed fish; however, the potential of dietary creatine to attenuate adverse effects caused by high-fat diets remains poorly understood. To address such gaps, this study was conducted to investigate the mitigating effect of dietary creatine on HFD-induced disturbance on growth performance, hepatic lipid metabolism, intestinal health and muscle quality of juvenile largemouth bass. Three diets were formulated: a control diet (10·20 % lipid), a high-fat diet (HFD, 18·31 % lipid) and HFD with 2 % creatine (HFD + creatine). Juvenile largemouth bass (3·73 (sem 0·01) g) were randomly assigned to three diets for 10 weeks. The key findings were as follows: (1) the expression of muscle growth-related genes and proteins was stimulated by dietary creatine, which contributes to ameliorate the adverse effects of HFD on growth performance; (2) dietary creatine alleviates HFD-induced adverse effects on intestinal health by improving intestinal health, which also enhances feed utilisation efficiency; (3) dietary creatine causes excessive lipid deposition, mainly via lipolysis and β-oxidation. Notably, this study also reveals a previously undisclosed effect of creatine supplementation on improving muscle quality. Together, for the first time from a comprehensive multiorgan or tissue perspective, our study provides a feasible approach for developing appropriate nutritional strategies to alleviate the adverse effects of HFD on farmed fish, based on creatine supplementation.
We investigate the dynamics of close-contact melting (CCM) on ‘gas-trapped’ hydrophobic surfaces, with specific focus on the effects of geometrical confinement and the liquid–air meniscus below the liquid film. By employing dual-series and perturbation methods under the assumption of small meniscus deflections, we obtain numerical solutions for the effective slip lengths associated with velocity $\lambda$ and temperature $\lambda _t$ fields, across various values of aspect ratio $\Lambda$ (defined as the ratio of the film thickness $h$ to the structure’s periodic length $l$) and gas–liquid fraction $\phi$. Asymptotic solutions of $\lambda$ and $\lambda _t$ for $\Lambda \ll 1$ and $\Lambda \gg 1$ are derived and summarised for different surface structures, interface shapes and $\Lambda$, which reveal a different trend of $\lambda$ for $\Lambda \ll 1$ and depending on the presence of a meniscus. In the context of constant-pressure CCM, our results indicate that longitudinal grooves can enhance heat transfer under the effects of confinement and a meniscus when $\Lambda \lesssim 0.1$ and $\phi \lt 1 - 0.5^{2/3} \approx 0.37$. For gravity-driven CCM, the parameters of $l$ and $\phi$ determine whether the melting rate is enhanced, reduced or nearly unaffected. We construct a phase diagram based on the parameter matrix $(\log _{10} l, \phi )$ to delineate these three regimes. Lastly, we derive two asymptotic solutions for predicting the variation in time of the unmelted solid height.
Mapping reviews (MRs) are crucial for identifying research gaps and enhancing evidence utilization. Despite their increasing use in health and social sciences, inconsistencies persist in both their conceptualization and reporting. This study aims to clarify the conceptual framework and gather reporting items from existing guidance and methodological studies. A comprehensive search was conducted across nine databases and 11 institutional websites, including documents up to January 2024. A total of 68 documents were included, addressing 24 MR terms and 55 definitions, with 39 documents discussing distinctions and overlaps among these terms. From the documents included, 28 reporting items were identified, covering all the steps of the process. Seven documents mentioned reporting on the title, four on the abstract, and 14 on the background. Ten methods-related items appeared in 56 documents, with the median number of documents supporting each item being 34 (interquartile range [IQR]: 27, 39). Four results-related items were mentioned in 18 documents (median: 14.5, IQR: 11.5, 16), and four discussion-related items appeared in 25 documents (median: 5.5, IQR: 3, 13). There was very little guidance about reporting conclusions, acknowledgments, author contributions, declarations of interest, and funding sources. This study proposes a draft 28-item reporting checklist for MRs and has identified terminologies and concepts used to describe MRs. These findings will first be used to inform a Delphi consensus process to develop reporting guidelines for MRs. Additionally, the checklist and definitions could be used to guide researchers in reporting high-quality MRs.
Rates of self-harm among children and young people (CYP) have been on the rise, presenting major public health concerns in Australia and worldwide. However, there is a scarcity of evidence relating to self-harm among CYP from culturally and linguistically diverse (CALD) backgrounds.
Aims
To analyse the relationship between self-harm-related mental health presentations of CYP to emergency departments and CALD status in South Western Sydney (SWS), Australia.
Method
We analysed electronic medical records of mental health-related emergency department presentations by CYP aged between 10 and up to 18 years in six public hospitals in the SWS region from January 2016 to March 2022. A multilevel logistic regression model was used on these data to assess the association between self-harm-related presentations and CALD status while adjusting for covariates and individual-level clustering.
Results
Self-harm accounted for 2457 (31.5%) of the 7789 mental health-related emergency department presentations by CYP; CYP from a CALD background accounted for only 8% (n = 198) of the self-harm-related presentations. CYP from the lowest two most socioeconomic disadvantaged areas made 63% (n = 1544) of the total self-harm-related presentations. Findings of the regression models showed that CYP from a CALD background (compared with those from non-CALD backgrounds) had 19% lower odds of self-harm (adjusted odds ratio 0.81, 95% CI 0.66–0.99).
Conclusions
Findings of this study provide insights into the self-harm-related mental health presentations and other critical clinical features related to CYP from CALD backgrounds that could better inform health service planning and policy to manage self-harm presentations and mental health problems among CYP.
In this paper, a capsule endoscopy system with a sensing function is proposed for medical devices. A single-arm spiral antenna is designed for data transmission and is combined with the voltage controlled oscillator to achieve sensing capabilities. The designed antenna operates at a 900 MHz industrial scientific medical band. By establishing a three-layer cylindrical model of the stomach, it was concluded that the antenna in the stomach has a high peak gain of −1.1 dBi. Additionally, the antenna achieved a −10 dB impedance bandwidth of 5%. The capsule endoscopy was experimentally measured in both actual stomach and simulated environments. The maximum working distance of the capsule endoscope was measured to be 6.8 m. Additionally, the proposed capsule endoscope was tested for its sensing function using solutions with different dielectric constants. Finally, it was confirmed through link analysis that it has good communication capabilities. The results and analysis confirm that the proposed capsule endoscope can be used for examining gastric diseases.
Acid-activated bentonites are utilized in many applications, including those that depend on their rheological properties and behavior, but little information is available regarding the rheological characteristics of this important industrial material. The purpose of this study was to investigate the effects of solids concentration, salt concentration, and pH value on the shear rate, shear stress, and other flow parameters of acid-activated bentonite suspensions. Activated Na-bentonite was prepared using sulfuric acid. Flow curves of the suspensions were modeled using the Herschel-Bulkley equation, which performed well for this system. The Herschel-Bulkley yield stress increased with the solids concentration and showed a maximum and minimum at the NaCl concentrations of 0.001 M and 0.01 M, respectively, and increased again slightly with further increases in NaCl concentration. The yield stress was at a maximum and a minimum at pH values of ≈5 and ≈7, respectively, followed by a slight increase with pH under alkaline conditions. The variations in dispersion rheological properties can be attributed to the change in the particle-association modes under different conditions.
This study aims at establishing a model for close-contact melting (CCM) of shear-thinning fluids. We presented a theoretical framework for predicting the variation of liquid melt film thickness and motion of unmelted solid for both Carreau and power-law fluids. We identified the appropriate energy equation considering the convective effect and derived an analytical temperature profile across the liquid film. Using the lubrication approximation, force equilibrium relationships and the corresponding numerical approaches were built. By using laser interferometry and photographic recording methods, we found excellent agreement between numerical solutions and experimental results for Carreau liquids, revealing that the convective effect weakens heat transfer and melting rate. We identified the critical liquid film thickness that determines three situations of CCM in the theoretical model for Carreau fluids. Numerical prediction demonstrated that the CCM of Carreau fluids can be almost equivalent to that of power-law fluids if the initial film thickness is greater than the critical value. Finally, approximate analytical models were developed for both Carreau and power-law models. For the applicability of the approximate analytical solutions, we derived two- and three-dimensional dimensionless phase diagrams of validity range and identified a key dimensionless group $(\varLambda Re)^{4/3}{Re}\left [3\ln (Ste+1)\right ]^{1/3}{Pe}^{-1/3}$, where $\varLambda$ is dimensionless characteristic time, Re is Reynolds number, Ste is Stefan number and Pe is Peclect number. The reliability of the approximate solutions was verified by comparing with the numerical results. These approximate solutions enable convenient and low-cost computational prediction of the dynamic CCM process of shear-thinning fluids.
A blunted hypothalamic–pituitary–adrenal (HPA) axis response to acute stress is associated with psychiatric symptoms. Although the prefrontal cortex and limbic areas are important regulators of the HPA axis, whether the neural habituation of these regions during stress signals both blunted HPA axis responses and psychiatric symptoms remains unclear. In this study, neural habituation during acute stress and its associations with the stress cortisol response, resilience, and depression were evaluated.
Methods
Seventy-seven participants (17–22 years old, 37 women) were recruited for a ScanSTRESS brain imaging study, and the activation changes between the first and last stress blocks were used as the neural habituation index. Meanwhile, participants' salivary cortisol during test was collected. Individual-level resilience and depression were measured using questionnaires. Correlation and moderation analyses were conducted to investigate the association between neural habituation and endocrine data and mental symptoms. Validated analyses were conducted using a Montreal Image Stress Test dataset in another independent sample (48 participants; 17–22 years old, 24 women).
Results
Neural habituation of the prefrontal cortex and limbic area was negatively correlated with cortisol responses in both datasets. In the ScanSTRESS paradigm, neural habituation was both positively correlated with depression and negatively correlated with resilience. Moreover, resilience moderated the relationship between neural habituation in the ventromedial prefrontal cortex and cortisol response.
Conclusions
This study suggested that neural habituation of the prefrontal cortex and limbic area could reflect motivation dysregulation during repeated failures and negative feedback, which might further lead to maladaptive mental states.
Paresis of muscle groups in patients with amyotrophic lateral sclerosis (ALS) tends to present split phenomena. We explored the split phenomenon of fasciculation in multiple antagonistic muscle groups in ALS patients.
Methods:
One hundred and forty ALS patients and 66 non-ALS patients were included from a single ALS center. Muscle ultrasonography (MUS) was performed to detect fasciculation in elbow flexor-extensor, wrist flexor-extensor, knee flexor-extensor, and ankle flexor-extensor. Split phenomena of fasciculation between different antagonistic muscle groups were summarized, and the possible influence factors were analyzed through stratified analysis.
Results:
The frequency of split phenomenon of fasciculation intensity was significantly higher than those of muscle strength (26.1% vs. 7.1% for elbow flexor-extensor, 38.3% vs. 5.7% for wrist flexor-extensor, 37.9% vs. 3.0% for knee extensor-flexor, and 33.6% vs. 14.4% for ankle flexor-extensor) (P < 0.01). For muscles with 0–1 level of muscle strength (the Medical Research Council, MRC, score), significance difference in mean fasciculation intensity was observed only in ankle flexor-extensor. For muscles with 2–5 level of muscle strength, significant dissociation of fasciculation grade was common, especially among patients with slow rapid progression rate and both upper and lower motor neuron (UMN and LMN) involvement. As for non-ALS patients, no significant difference was observed in fasciculation intensity between antagonistic muscles.
Conclusion:
Split phenomenon of fasciculation between antagonistic muscles was common and relatively specific in ALS patients. Muscle strength, progression rate, and UMN involvement were influence factors of the split phenomenon of fasciculation intensity.
Climbing robots that use bionic claws can climb vertical or even inverted rough surfaces. However, wall-climbing robots with unidirectional spiny feet cannot crawl horizontally or downward on vertical rough surfaces. In this paper, a pair of gripping spiny feet is used to give a robot the capacity to crawl in any direction on a rough wall. On the basis of observations of the gecko’s method for grasping onto a vertical rough surface, a multilevel interlocking structure is proposed. A spherical contact model of the claw tip on a vertical rough surface is established, and the influences of the contact angle, friction coefficient, and other factors on the grappling claw action are analyzed. Moreover, the optimal structure of the grappling claws is proposed. The force during the grasping and detachment of the mechanism and the influence of the number of feet on grasping performance are determined through experiments. Furthermore, a six-legged wall-climbing robot is designed and evaluated in terms of crawling on a vertical rough surface at various angles. The feasibility of using an opposed gripping mechanism to allow a robot to crawl in any direction on a vertical rough surface is also verified.
Flavonoids are a group of phenolic secondary metabolites in plants that have important physiological, ecological and economic value. In this study, using the desert plant Artemisia sphaerocephala Krasch. as the sample material, the content and components of the total flavonoids in its seeds at seven different developmental stages were determined. In addition, the genes involved in flavonoid metabolism were identified by full-length transcriptome sequencing (third-generation sequencing technology based on PacBio RS II). Their expression levels were analysed by RNA-seq short reading sequencing, to reveal the patterns and regulation mechanisms of flavonoid accumulation during seed development. The key results were as follows: the content of total flavonoids in mature seeds was 15.05 mg g−1, including five subclasses: flavonols, chalcones, flavones, flavanones and proanthocyanidins, among which flavonols accounted for 45.78%. The period of rapid accumulation of flavonoids was 40–70 d following anthesis. The high expression of phenylalanine ammonia-lyase (PAL), 4-coumarate-CoA ligase (4CL) and UDP-glucose:flavonoids 3-o-glucosyltransferase (UF3GT) promoted the accumulation of total flavonoids, while the high expression of flavonoids 3′-hydroxylase (F3′H) and flavonols synthase (FLS) made flavanols the main component. Transcription factors such as the MYB-bHLH-WDR (MBW) complex and Selenium-binding protein (SBP) directly regulated the structural genes of flavonoid metabolism, while C2H2-type zinc finger (C2H2), Zinc-finger transcription factor (GATA), Dehydration-responsive element binding (DREB), Global Transcription factor Group E protein (GTE), Trihelix DNA-binding factors (Trihelix) and Phytochrome-interacting factor (PIF) indirectly promoted the synthesis of flavonoids through hormones such as brassinoidsteroids (BRs) and abscisic acid (ABA). These results provided valuable resources for the application of related genes in genetics and breeding.
A deep ice core was drilled at Dome A, Antarctic Plateau, East Antarctica, which started with the installation of a casing in January 2012 and reached 800.8 m in January 2017. To date, a total of 337 successful ice-core drilling runs have been conducted, including 118 runs to drill the pilot hole. The total drilling time was 52 days, of which eight days were required for drilling down and reaming the pilot hole, and 44 days for deep ice coring. The average penetration depths of individual runs were 1 and 3.1 m for the pilot hole drilling and deep ice coring, respectively. The quality of the ice cores was imperfect in the brittle zone (650−800 m). Some of the troubles encountered are discussed for reference, such as armoured cable knotting, screws falling into the hole bottom, and damaged parts, among others.
Emergency search and rescue on the sea is an important part of national emergency response for marine perils. Optimal route planning for maritime search and rescue is the key capability to reduce the searching time, improve the rescue efficiency, as well as guarantee the rescue target’s safety of life and property. The main scope of the searching route planning is to optimise the searching time and voyage within the constraints of missing search rate and duplicate search rate. This paper proposes an optimal algorithm for searching routes of large amphibious aircraft corresponding to its flight characteristics and sea rescue capability. This algorithm transforms the search route planning problem into a discrete programming problem and applies the route traceback indexes to satisfy the duplicate search rate and missing search rate.
p53, DNA damage regulated gene (PDRG) and apoptosis-stimulating p53 protein 2 (ASPP2) are p53-related genes which can promote apoptosis. The full-length cDNA sequence of the Px-pdrg and Px-aspp2 genes were characterized and their mRNA expression dynamics under heat stress were studied in diamondback moth (DBM) Plutella xylostella collected from Fuzhou, China. The full-length cDNA of Px-pdrg and Px-aspp2 spans 721 and 4201 bp, containing 395 and 3216 bp of the open reading frame, which encode a putative protein comprising 130 and 1072 amino acids with a calculated molecular weight of 14.58 and 118.91 kDa, respectively. As compared to 25°C, both Px-pdrg and Px-aspp2 were upregulated in chlorpyrifos-resistant (Rc) and -susceptible (Sm) strains of DBM adults and pupae under heat stress. In addition, Rc DBM showed a significantly higher expression level of Px-pdrg and Px-aspp2 in contrast to Sm DBM. The results indicate that high temperature can significantly promote apoptosis process, especially in Rc-DBM. Significant fitness cost in Rc-DBM might be associated with drastically higher transcript abundance of Px-pdrg and Px-aspp2 under the heat stress.
This research paper addresses the hypothesis that Septin6 is a key regulatory factor influencing amino acid (AA)-mediated cell growth and casein synthesis in dairy cow mammary epithelial cells (DCMECs). DCMECs were treated with absence of AA (AA−), restricted concentrations of AA (AAr) or normal concentrations of AA (AA+) for 24 h. Cell growth, expression of CSN2 and Septin6 were increased in response to AA supply. Overexpressing or inhibiting Septin6 demonstrated that cell growth, expression of CSN2, mTOR, p-mTOR, S6K1 and p-S6K1 were up-regulated by Septin6. Furthermore, overexpressing or inhibiting mTOR demonstrated that the increase in cell growth and expression of CSN2 in response to Septin6 overexpression were inhibited by mTOR inhibition, and vice versa. Our hypothesis was supported; we were able to show that Septin6 is an important positive factor for cell growth and casein synthesis, it up-regulates AA-mediated cell growth and casein synthesis through activating mTORC1 pathway in DCMECs.
To determine the prevalence of Cryptosporidium in dairy cattle in Guangdong Province, South China, 1440 fecal samples were collected from 10 farms and screened for Cryptosporidium with PCR. The overall prevalence of Cryptosporidium was 4.38% (63/1440), and the infection rates in preweaned calves, postweaned calves, heifers and adults were 6.4% (19/297), 6.19% (33/533), 1.48% (4/271) and 2.06% (7/339), respectively. Three Cryptosporidium species, Cryptosporidium andersoni (n = 33), Cryptosporidium bovis (n = 22) and Cryptosporidium ryanae (n = 8) were detected by DNA sequence analysis of the 63 positive samples, and C. andersoni was identified as the most common species on the dairy cattle farms. In preweaned calves, C. bovis was the most prevalent species (9/19, 47.4%). In contrast, C. andersoni was the predominant species (19/33, 57.6%) in postweaned calves and the only species found in heifers and adults. The zoonotic species Cryptosporidium parvum was not detected in this study. Twenty-four C. andersoni isolates were successfully classified into three multilocus sequence typing (MLST) subtypes. MLST subtype A4,A4,A4,A1 was the predominant subtype, and MLST subtype A2,A5,A2,A1, previously found in sheep, was detected in cattle for the first time. A linkage disequilibrium analysis showed that the C. andersoni isolates had a clonal genetic population structure. However, further molecular studies are required to better understand the epidemiology of Cryptosporidium in Guangdong.
Training students has been proven to be the optimal way to deliver cardiopulmonary resuscitation (CPR) skills. However, it is somehow unknown whether or not the current recommendations appropriate for Caucasian students are also suitable for East Asian students. The purpose of this study is to explore the best age for East Asian students to receive CPR training.
Methods
Students were recruited from six schools. Students participated in a standard CPR training program provided by tutors. Each student attended a 60-minute training session with a manikin. After being trained, within one hour, the student’s compression quality was assessed.
Results
A total of 360 students who constituted 12 continuous grades were recruited for this study. Adequate compression depth and satisfactory compression rate with correct hand position could be achieved since the age of 12. However, successful compression rate and complete release could be achieved since the younger age of six.
Conclusions
Current recommendations for Caucasian students to cultivate a full-capacity CPR rescuer at the age of 12 are also appropriate for East Asian students. However, the optimal age for students to receive CPR training should be decided based on evidence and importance assessment of CPR.
He D, Huang K, Yang Y, Jiang W, Yang N, Yang H. What is the optimal age for students to receive cardiopulmonary resuscitation training? Prehosp Disaster Med. 2018;33(4):394–398.
OBJECTIVES/SPECIFIC AIMS: To compare the accuracy and precision for estimating the diagnostic accuracies (sensitivities and specificities) between differential verification (DV) and partial verification (PV) methods. Comparisons were made under scenarios with different values of design parameters including disease prevalence, proportion of verification for positive results, proportion of verification for negative result, sensitivity and specificity of the brass standard (BS) test in DV method. Through comparing 2 different verification methods under different scenarios, we give suggestions that which verification method is optimal under different design settings. METHODS/STUDY POPULATION: For both PV and DV methods, simulation studies were performed using statistical package R, version 3.1.3. We were primarily interested in studying how the unbiasedness and precision for estimation of diagnostic accuracies (sensitivity and specificity) of an index test change with the following design parameters: disease prevalence, proportion of verification for positive test results, the proportion of verification for negative test results, and the sensitivity and specificity of a BS test. We chose different values for each of the above parameters. For each estimation, we allowed values in only 1 parameter to change by fixing the other 2 parameters, so that the effect of each design parameter on the unbiasedness and precision of both sensitivity and specificity can be determined. For the DV method, we also developed an analytical method to estimate the sensitivity and specificity of an index test using a quadratic equation with a unique solution of the specificity and sensitivity. RESULTS/ANTICIPATED RESULTS: For rare disease with prevalence less than 1%, the PV method resulted in a less biased and more precise estimate of sensitivities and specificities of the index test. If the disease prevalence was between 1% and 10%, the DV method using a BS test with moderate or high sensitivity and specificity (sensitivity and specificity >90%) resulted in a less biased and more precise estimate of diagnostic accuracies of the index test. When the disease prevalence was greater than 10%, the PV method was superior when the BS test had sensitivity and specificity <80%, and the DV method was superior when the BS test had both sensitivity and specificity >90%. When the proportion of verification of positive test results was <30% or >70%, the DV method yielded smaller bias for the estimated specificity than the PV method. However, the PV method generated a much smaller mean square error (MSE) for specificity than the DV method when the proportion of verification for positive test results was >50%. Although the disease prevalence was >10% and the proportion of verification of positive test results was <30%, the DV method resulted in a smaller MSE for specificity. DISCUSSION/SIGNIFICANCE OF IMPACT: Disease prevalence and proportions of verification for patients with positive and negative test results influence the accuracy of a new diagnostic test. If a new index test for a very rare disease is evaluated, the PV method should be used for assessing the performance of the index test. When a disease prevalence is >1%, the DV method will result in a less biased and more precise estimate of diagnostic accuracy of an index test, if the BS test itself used in the DV method has large specificity and specificity. One concern of using BS test for the DV method is the clinical cost. Depending on the disease type, the BS tests usually are imperfect, but may be less aggressive and/or less expensive than the gold standard test. Moreover, as all clinical examinations require professional personnel to perform, verification of the index test for relative large proportion of a large cohort of patients could become a burden on human resources. Thus, the future research of the optimal design method for a diagnostic accuracy study should be based on the comprehensive cost-effectiveness analysis.
OBJECTIVES/SPECIFIC AIMS: The goal of the study is to evaluate the prognostic importance and accuracies of a biomarker, human epidermal receptor 2 (Her2), for breast cancer recurrence in a cohort study, namely Lifetime after Cancer Epidemiology (LACE). We specifically interested in the role that Her2 plays in prognosis of breast tumor recurrence for women after a previously diagnosed and treated breast cancer. METHODS/STUDY POPULATION: The study cohort includes 2267 women enrolled in LACE who had previously diagnosed breast cancer. Patients were enrolled from each of the 2 LACE registries in California and Utah. The main endpoint of the study is the right-censored time to breast cancer recurrence. Patients’ enrollments were, on average, 2 years after diagnosis of the first breast cancer. The patients’ characteristics at baseline were obtained through self-administered questionnaires. Cox proportional hazard model with time-varying covariates was used to relate the Her2 status (Her2+ and Her2−) to the primary end point (time to breast cancer recurrence). Hazard ratios (HRs) and their 95% confidence interval comparing Her2+ and Her2− arms were estimated. Time-dependent sensitivity and specificity were used to investigate the performance of using Her2 for classifying patients into high and low risk (Her2 + is classified as hi risk and Her− as low risk) of future breast cancer recurrence at time points after baseline. The time-dependent sensitivity was calculated as the proportion of patients being classified as high risk of recurrence who had breast cancer recurrence before a series of pre-specified time points after baseline, and the time-dependent specificity was calculated as the proportion of subjects being classified as low risk of recurrence who did not have breast cancer recurrence at the same time points. RESULTS/ANTICIPATED RESULTS: The average patient follow-up time was 9.8 years, and 18% of the women got positive Her2 test results at baseline. Among 2267 patients in the study cohort, 2031 had records on their Her2 status, among whom 326 (16.1%) patients were Her2+ and 1705 (83.9%) were Her2−. The mean tumor size among the 2031 patient was 2.10±1.22 cm. A majority of the patients (78.9%) were White. Over one-half of these patients were neither current nor past smokers. Only 3% of the patient had a baseline stage IIIA or higher. About 49% of the patients underwent a mastectomy. Radiation therapy was used by 63.5% of the patients, and Tamoxifen users accounted for 78% of the study cohort. We found a statistically significant association between Her2 and breast cancer recurrence (HR=1.33, log-ran p-value=0.006). However, the HRs of breast cancer recurrence comparing Her2+ and Her2− patients decreased over time. We also investigate the effect of combined Her2, estrogen (ER), and progesterone (PR) on breast cancer recurrence and found that patients with Her2+/ER+/PR− had the highest risk of breast cancer recurrence. The hazard of recurrence for this group of patients was 85% higher than patients with Her2−/ER+/PR+. We also investigate the prognostic accuracies of Her2 in terms of time-dependent sensitivity and specificity. Using Her2 as the prognostic biomarker resulted in a specificity consistently over 80% from baseline up until 15 years post-baseline. The time-dependent sensitivity of Her2 was above 90% between baseline and 1.5 years. Then, the sensitivity dropped gradually to 40% from 1.5 years to 3 years post-baseline. For prognosis of breast cancer over 3 years from baseline, the sensitivity was between 30% and 40%. DISCUSSION/SIGNIFICANCE OF IMPACT: As a single biomarker and risk factor, Her2 was statistically significantly associated with the recurrence of breast cancer among patients in the LACE cohort. A composite biomarker by combining Her2, ER, and PR status was also significantly associated with the breast cancer recurrence. However, the HRs of breast cancer recurrence comparing Her2+ and Her2− patients decreased over time, implying that the Her2 status had a high impact on early recurrent breast tumors. Single biomarkers, usually, have very limited ability for prognosis of future events. However, we found that using HER2 as a single biomarker can give a relatively larger specificity consistently over 15 years of the study period. The sensitivity of Her2 is high for detecting early breast cancer recurrence. However, after 2.5 years from baseline, using Her2 for breast cancer recurrence detection is not reliable. Due to the relatively high accuracies of using Her2 status for prognosis of breast cancer recurrence, we conclude that Her2 should be considered in clinical studies related to prognosis of breast cancer recurrence. Future studies will investigate if prognostic accuracies can be improved by combining Her2 with baseline clinical risk factors such as age, tumor size and lymph nodes. In conclusion, our study has the clinical impact on prognosis (or early detection) of breast cancer recurrence among women with previously diagnosed and treated breast cancers.