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Background. Pulmonary artery hypertension (PAH) is a common complication of congenital heart disease (CHD) and is associated with worse outcomes and increased mortality. The Doppler echocardiography (DE) is a commonly used imaging tool for both diagnosis and follow-up examination of PAH. Here is to evaluate the diagnostic performance of DE combined with NTproBNP/BNP as screening strategy in PAH patients with CHD. Methods. A retrospective study in 64 patients with CHD has been carried out to compare estimate pulmonary artery systolic pressure (PASP) measured with DE to that measured with right heart catheterization (RHC). The Pearson correlation analyses were used to calculate the correlation coefficients between RHC and DE. The Bland-Altman analyses were carried out to assess the agreement between the two methods. ROC analyses were used to evaluate the diagnostic performance of DE, NTproBNP/BNP, and DE combined with NTproBNP/BNP. Results. Our data have demonstrated that a mild correlation ( r = 0.4401 , P < 0.01 ) was observed between PASP ( 78.1 ± 29.0 mmHg) measured during RHC and PASP ( 74.9 ± 19.7 mmHg) as estimated using DE. The Bland-Altman analysis demonstrated that the bias for DE PASP estimates was 3.2 mmHg with 95% limits of agreement ranging from -49.53 to 55.90 mmHg. The results of DE showed an AUC of 0.848 (95% CI = 0.666 -1; P < 0.001 ), the sensitivity of which was 98.3% and the specificity was 77.8%. The AUC of NTproBNP/BNP for the identification of PAH was 0.804 (95% CI = 0.651 -0.956; P < 0.001 ), the sensitivity of which was 81.4% and the specificity was 87.5%. The AUC of DE combined with NTproBNP/BNP was 0.857 (95% CI = 0.676 -1; P < 0.001 ), of which sensitivity was 100% and specificity was 77.8%. The positive predictive value (PPV) and negative predictive value (NPV) were 96.6% and 100%, respectively. Conclusions. Our study shows that the Doppler echocardiography combined with NTproBNP/BNP has better diagnostic performance in pulmonary artery hypertension associated with congenital heart disease, especially when DE negative screening in PAH patients.

A new indole-diterpenoid, penijanthine E (

Microwave vectorial near-field precision physical quantity sensing using ensembles of nitrogen vacancy (NV) centers in diamond has attracted much interest in recent years. The quantum probe of a micron-sized diamond particle attached to a tapered fiber has been widely studied for applications in condensed matter physics, bioscience and electromagnetics. A general issue of Microwave (MW) field vectorial sensing using the probe describe above is the orientation of the NV axes to specified directions in the lab frame. In this work, we propose a practical method for characterizing the MW vectorial near-field by using the quantum probe. The orientations of the NV axes in the lab frame are measured first by using 3-axis Helmholtz coils. The NV axis also needs to be rotated to any specified direction for sensing the MW vectorial near-field component on the perpendicular plane. We demonstrate coplanar waveguide (CPW) vectorial near-field characterization using this micrometer-sized probe, and the proposed method is expected to be applied in the field of millimeter wave imaging with nanometer spatial resolution.

Background Aortic stenosis is a common heart valvular disease whose pathological processes include an inflammatory reaction and lipid accumulation. However, its detailed pathogenesis is yet to be completely elucidated. Therefore, it is of great significance to further explore the molecular mechanisms of aortic stenosis. Methods Four datasets were downloaded from the Gene Expression Omnibus (GEO) database. Firstly, the differently expressed genes (DEGs) were screened between control and aortic stenosis samples. Secondly, weighted gene co-expression network analysis (WGCNA) was performed to find the highly relevant gene modules. Enrichment analysis and protein-protein interaction (PPI) networking were also performed, then Cytoscape was used to identify hub genes. Finally, the six participants (3 control participants and 3 patients with aortic stenosis) were recruited at the Tianjin Chest Hospital. In order to verify the expression level of USP14, several molecular experiments were performed, including hematoxylin-eosin (HE) staining, immunohistochemistry, immunofluorescence technology, real time-quantitative polymerase chain reaction (RT-qPCR), and western blotting. Results A total of 9636 DEGs were found between the control and aortic stenosis samples. The DEGs were mainly enriched in the autophagy-animal, cellular lipid catabolic process, apoptosis, and glycoside metabolic process categories. Eleven hub genes were identified via four different algorithms. Following verification of the patient samples, Ubiquitin-specific protease 14 (USP14) was found to be displayed at higher levels in the aortic stenosis samples. Conclusion USP14 might be involved in the occurrence and development of aortic stenosis, so it would be a molecular target for early diagnosis and specific treatment of aortic stenosis. There is a significant association between the high expression of USP14 and aortic stenosis, indicating that this gene may be a genetic risk factor for aortic stenosis.

A new indole-diterpenoid, penijanthine E (1), and a known analogue (2), were obtained from the PDB culture of the marine-derived fungus Penicillium citrinum ZSS-9. The absolute configuration of 1 was elucidated by calculated TDDFT ECD and DP4plus calculations. The absolute configuration of 2 was confirmed by single-crystal X-ray diffraction analysis and TDDFT ECD calculations. Compounds 1 and 2 showed antiviral activity against influenza A virus (IAV) of A/WSN/33(H1N1) and A/PR/8/34(H1N1) strains with IC50 values ranging from 12.6 to 46.8 μM.

BACKGROUND: Liriodendrin is a therapeutic constituent of sargentgloryvine stem which is a famous Chinese traditional medicine. Previous studies have suggested liriodendrin could inhibit different pathways to treat inflammation in lung and intestinal tract. But whether it can treat myocardial infarction (MI) is unknown. We investigated the protective effect of liriodendrin on acute MI in rats and explored the specific mechanisms to expand the use of this traditional Chinese medicine. METHODS: The rats were randomized into the sham group (sham operation), control group (ligation of the left anterior descending artery), and liriodendrin group. The liriodendrin group was intragastrically administered with a liriodendrin solution (100 mg/kg). The control group and the sham group were intragastrically administered with normal saline. Before all rats were euthanized, echocardiography was used to detect their cardiac function. Hematoxylin and eosin (HE) staining and the terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) method were performed. Further quantitative detection of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels in tissues were also detected. Western Blot and real-time polymerase chain reaction (RT-PCR) were used to detect the apoptosis and nuclear factor kappa-B (NF-κB) pathway in tissues. H9C2 cells were used to detect the related mechanisms in vitro. RESULTS: Echocardiography showed that, compared to control group, the cardiac function of the liriodendrin group was significantly improved. histopathological staining of the control group showed that the myocardial tissue was severely damaged, and inflammatory cells were infiltrated. Compared to the control group, the apoptosis index of the liriodendrin group was significantly lower (P

Objective To explore the effect of lipoprotein(a) [Lp(a)] on in-stent restenosis and non-target coronary lesions in coronary artery disease (CAD) patients implanted with drug-eluting stents. Methods One hundred and seventy-four patients, diagnosed as CAD and underwent percutaneous coronary intervention (PCI) with the implantation of drug-eluting stents (DES), were enrolled in present study; all of them were performed another elective PCI or revascularization within 1-4 years after their previous procedures. Thirty-one of enrolled patients were discovered to have in-stent restenosis. The relationship between Lp(a) and in-stent restenosis and the development of non-target coronary lesions were analyzed in groups stratified by the presence of in-stent stenosis or Lp(a) levels, and the independent risk factors of both in-stent restenosis and non-target lesions were also analyzed by multivariate logistic regression analysis. Results In CAD patients with DES, Lp(a) level in patients with in-stent restenosis showed a significant increase than those with the Lp(a) level non-restenosis [(437.57±391.60) mg vs. (279.46±288.06) mg, P=0.04]. In following analysis comparing lipid profiles and coronary angiography results between low and high Lp(a) groups, the percentage of triple-vessel disease and left main plus triple-vessel disease appeared to be statistically higher in high Lp(a) group than those in low Lp(a) group (P=0.022). Multivariate logistic regression analysis revealed that high level of Lp(a) and much number of stents implanted were the independent risk factors for in-stent restenosis of DES. In comparing the characteristics of coronary angiography and results of quantitative coronary angiography, number of cases with non-target lesions, presence of in-stent restenosis, minimal lumen diameter and in-stent late lumen loss were all significantly higher in high Lp(a) group than those in low Lp(a) group (P

DNA methylation of anthocyanin biosynthesis-related genes and MYB/bHLH transcription factors was associated with apple fruit skin color revealed by whole-genome bisulfite sequencing. DNA methylation is a common feature of epigenetic regulation and is associated with various biological processes. Anthocyanins are among the secondary metabolites that contribute to fruit colour, which is a key appearance and nutrition quality attribute of apple fruit. Although few studies reported that DNA methylation in the promoter of MYB transcription factor was associated with fruit skin color, there is a general lack of understanding of the dynamics of global and genic DNA methylation in apple fruit. Here, whole-genome bisulfite sequencing was carried out in fruit skin of apple (Malus domestica Borkh.) cv. ‘Red Delicious’ (G0) and its four-generation bud sport mutants, including ‘Starking Red’ (G1), ‘Starkrimson’ (G2), ‘Campbell Redchief’ (G3) and ‘Vallee spur’ (G4) at color break stage. Correlation and linear-regression analysis between DNA methylation level and anthocyanin content, as well as the transcription levels of genes related to anthocyanin biosynthesis were carried out. The results showed that the number of differentially methylated regions (DMRs) and differentially methylated genes (DMGs) was considerably increased from G1 to G4 versus the number observed in G0. The mCHH context was dominant in apple, but the levels of mCG and mCHG of DMGs were significantly higher than that of the mCHH. Genetic variation of bud sport mutants from ‘Red Delicious’ was associated with differential DNA methylation. Additionally, hypomethylation of mCG and mCHG contexts in flavonoid biosynthesis pathway genes (PAL, 4CL, CYP98A, PER, CCoAOMT, CHS, and F3′H), mCHG context in MYB10 at upstream, led to transcriptional activation and was conductive to anthocyanin accumulation. However, hypermethylation of mCG context in bHLH74 at upstream led to transcriptional inhibition, inhibiting anthocyanin accumulation.

Chronic stress refers to the non-specific systemic reaction that occurs when the body is stimulated by various internal and external negative factors over a long time. The physiological response to chronic stress exposure has long been recognized as a potent modulator in the occurrence of atherosclerosis. Furthermore, research has confirmed the correlation between atherosclerosis and cardiovascular events. Chronic stress is pervasive during negative life events and may lead to the formation of plaque. Several epidemiological studies have shown that chronic stress is an independent risk factor for the development of vascular disease and for increased morbidity and mortality in patients with pre-existing coronary artery disease. One possible mechanism for this process is that chronic stress causes endothelial injury, directly activating macrophages, promoting foam cell formation and generating the formation of atherosclerotic plaque. This mechanism involves numerous variables, including inflammation, signal pathways, lipid metabolism and endothelial function. The mechanism of chronic stress in atherosclerosis should be further investigated to provide a theoretical basis for efforts to eliminate the effect of chronic stress on the cardiocerebral vascular system.

Objective To analyze the correlation between D-dimer/fibrinogen (D/F) ratio, hypersensitive C-reactive protein (hs-CRP) level and the severity of coronary stenosis and illness in patients with acute coronary syndrome (ACS), and explore the clinical application value of D/F ratio. Methods The case data of 443 patients undergone coronary angiography in the Department of Cardiology, Nanfang Hospital, Southern Medical University during Jan. 2014 to Dec. 2017 were collected, and then the patients were divided into normal group, stable angina pectoris (SAP) group and acute coronary syndrome (ACS) group. The ACS group was divided into single-vessel disease group, double-vessel disease group and triple-vessel disease group according to the number of coronary lesions and into high Gensini score group and low Gensini score group according to the median of Gensini score. The correlations of D-dimer, fibrinogen, D/F ratio and hs-CRP with ACS were compared respectively, and then analyzing the predictive value for diagnosis of ACS and evaluation of lesion severity. Results The overall trend of D-dimer, fibrinogen and hs- CRP was normal group 0.05). Multivariate logistic regression analysis revealed that D/F ratio and hs-CRP were independent risk factors for high Gensini score in ACS patients (OR=1.136, P=0.045; OR=1.197, P

Background Vein graft restenosis (VGR), which appears to be caused by dyslipidemia following vascular transplantation, seriously affects the prognosis and long-term quality of life of patients. Methods This study analyzed the genetic data of restenosis (VGR group) and non-stenosis (control group) vessels from patients with coronary heart disease post-vascular transplantation and identified hub genes that might be responsible for its occurrence. GSE110398 was downloaded from the Gene Expression Omnibus database. A repeatability test for the GSE110398 dataset was performed using R language. This included the identification of differentially expressed genes (DEGs), enrichment analysis via Metascape software, pathway enrichment analysis, and construction of a protein–protein interaction network and a hub gene network. Results Twenty-four DEGs were identified between VGR and control groups. The four most important hub genes ( KIR6.1, PCLP1, EDNRB, and BPI) were identified, and Pearson’s correlation coefficient showed that KIR6.1 and BPI were significantly correlated with VGR. KIR6.1 could also sensitively predict VGR (0.9 Conclusion BPI and KIR6.1 were differentially expressed in vessels with and without stenosis after vascular transplantation, suggesting that these genes or their encoded proteins may be involved in the occurrence of VGR.

The WALL ASSOCIATED-KINASE - RECETOR-LIKE KINASE (WAK-RLK) gene family has been reported to act as a sensor for disease. Apple (Malus domestica) can be affected by multiple biotic stresses, such as fungal diseases from Valsa mali (Vm), Alternariaalternata Apple Pathotype (AaAP), and Pythium ultimum (Pu). However, there has been no report of WAK-RLK genes involved in apple biotic stress response. In this paper, we performed a comprehensive study including genome-wide annotation, characterization and gene expression analysis of WAK-RLKs in apple (MdWAK-RLKs). We found 44 members based on structural domain identification. The number of amino acids, molecular weight, and theoretical pI of these identified members ranged from 302 to 998, 33.63 to 110.35 kD, and 5.1 to 9.26, respectively. Members of the family were anchored to 16 out of 17 chromosomes and were classified into six phylogenetic groups. We found two phylogenetic groups specific to the apple genome. Synteny analysis revealed that 11 gene pairs arose from segmental duplications and 7 gene clusters resulted from tandem duplications. Cis-elements in the promoter region of MdWAK-RLKs were found mainly in response to circadian rhythm, hormones, and multiple stresses. The large number of members that showed high expression in multiple tissues and differential expressed in response to stress revealed that the different functional roles of MdWAK-RLKs under physiological or pathological conditions. Several genes, such as MDP0000278283, MDP0000153539, MDP0000170906, and MDP0000251865, were significantly influenced by multiple diseases. This study provides new insights into the potential function of WAK-RLKs in Malus and in Rosaceae and its contribution to disease resistance.

Objective To investigate the effect of serous amyloid P (SAP) component on serum paraoxonase 1 (PON1) activity, serum monocyte chemotactic protein 1 (MCP-1) expression and atherosclerosis progression in ApoE-/- mice, and explore the possible mechanisms thereof. Methods Six male C57/BL6 mice were fed with chow diet as normal control group. Twelve male ApoE-/- mice fed with western diet for 12 weeks were used to establish animal models of atherosclerosis, and then randomly divided into two groups (6 each): SAP and PBS group. Mice in SAP group were treated (i.p.) with SAP (6mg/g) every other day from day 0 to day 14. Mice in normal and PBS group were treated (i.p.) with PBS (same volume as SAP group) every other day from day 0 to day 14. The blood specimen and aorta vascular tissues were collected at the 16th week after the first immunization. Serum lipids and PON1 activity were assessed. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of serum SAP and MCP-1. Hematoxylin-eosin (HE) staining was used to observe the formation of atherosclerotic plaque. Oil red O staining was performed to observe the lipid accumulation, and immunohistochemical staining was performed to detect the SAP expression in the atherosclerotic plaque. Results Compared with the normal group, the serum PON1 activity reduced significantly while MCP-1 expression increased (P

Bud sport mutants of apple (Malus domestica Borkh.) trees with a highly blushed colouring pattern are mainly caused by the accumulation of anthocyanins in the pericarp. Hormones are important factors modulating anthocyanin accumulation. However, a good understanding of the interplay between hormones and anthocyanin synthesis in apples, especially in mutants at the molecular level, remains elusive. Here, physiological and comparative transcriptome approaches were used to reveal the molecular basis of pericarp pigmentation in ‘Red Delicious’ and its mutants, including ‘Starking Red’, ‘Starkrimson’, ‘Campbell Redchief’ and ‘Vallee spur’, which were designated G0 to G4, respectively. Pericarp pigmentation gradually proliferated from G0 to G4. The anthocyanin content was higher in the mutants than in ‘Red Delicious’. The activation of early phenylpropanoid biosynthesis genes, including ASP3, PAL, 4CL, PER, CHS, CYP98A and F3’H, was responsible for anthocyanin accumulation in mutants. In addition, IAA and ABA had a positive regulatory effect on the synthesis of anthocyanins, while GA had the reverse effect. The down-regulation of AACT1, HMGS, HMGR, MVK, MVD2, IDI1 and FPPS2 involved in terpenoid biosynthesis influences anthocyanin accumulation by positively regulating transcripts of AUX1 and SAUR that contribute to the synthesis of IAA, GID2 to GA, PP2C and SnRK2 to ABA. Furthermore, MYB and bHLH members, which are highly correlated (r=0.882–0.980) with anthocyanin content, modulated anthocyanin accumulation by regulating the transcription of structural genes, including CHS and F3’H, involved in the flavonoid biosynthesis pathway.

The aim of this study was to observe the effect of a formulation of traditional Chinese medicine extracts known as Xingnaojia (XNJ) on the liver function, learning ability and memory of rats with chronic alcoholism and to verify the mechanism by which it protects the brain and liver. A rat model of chronic alcoholism was used in the study. The spatial learning ability and memory of the rats were tested. The rats were then sacrificed and their brains and hepatic tissues were isolated. The activity of superoxide dismutase (SOD) and levels of glutamate (Glu), N-methyl D-aspartate receptor subtype 2B (NR2B), cyclin-dependent kinase 5 (CDK5) and cannabinoid receptor 1 (CB1) in the hippocampus were analyzed. The ultrastructure of the hepatic tissue was observed by electron microscopy. In addition, the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in serum were tested and the levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG) and total cholesterol (TCHOL) were analyzed. XNJ enhanced the learning and memory of rats with chronic alcoholism. Treatment with XNJ increased the activity of SOD, and decreased the expression levels of NR2B mRNA and NR2B, CB1 and CDK5 proteins in the brain tissues compared with those in the model rats. It also increased the activity of ALDH in the serum and liver, decreased the serum levels of LDL, TG and TCHOL and increased the serum level of HDL. These results indicate that XNJ exhibited a protective effect against brain and liver damage in rats with chronic alcoholism.

Destruction of bridge expanded joint is a serious problem for concrete bridge. Based on 5 years measured data, the temperature in the different positions of the concrete box girder was systemically analyzed to illuminate the cause of the bridge expanded joint damage. A method for predicting the extremum value of the temperature difference of concrete girder was proposed by use of the extrema analysis and curve fitting based on the temperature in the different positions of the concrete box girder. The relationship is quite useful in estimating the destruction of bridge expanded joint by effective temperature difference in concrete box-girder.

The high density lipoprotein (HDL) in human plasma is a heterogeneous lipoprotein consisting of roughly equal contents of lipid and protein in roughly equal content, and it consists of several subtypes. HDL possesses several well-documented functions, including anti-atherosclerosis by promoting reverse cholesterol transport, inhibiting the oxidative modification of low density lipoproteins (LDLs), inhibiting vascular inflammation, preventing thrombosis and apoptosis, and promoting endothelial repair. Recently, more cardiovascular protective functions of HDL have been found, mainly including the ability of suppressing immune inflammatory reaction, inhibiting the proliferation of hematopoietic stem cells, and regulating the plasma glucose level. It is of great importance to understand how different HDL subtypes contribute to the potentially cardioprotective functions. DOI: 10.11855/j.issn.0577-7402.2014.11.13

OBJECTIVE: To compare the value of apolipoprotein B (apoB) and low-density lipoprotein cholesterol (LDL-C) in assessing the risk of coronary heart disease in patients with inconsistent apoB and LDL-C levels. METHODS: In a total of 603 patients undergoing coronary angiography, apoB and LDL-C levels were categorized into high and low levels relative to the median levels of apoB and LDL-C, based on which the patients were divided into 4 groups with low apoB/low LDL-C, low apoB/ high LDL-C, high apoB/ low LDL-C, or high apoB/high LDL-C. According to the results of coronary angiography, we evaluated the number of coronary artery branches with lesions and the severity of coronary artery stenosis in the 4 groups to assess the correlation of apoB and LDL-C with cardiovascular risks. RESULTS: We found significant differences in the number of coronary artery branches with lesions and the severity of coronary artery stenosis among the 4 groups (P < 0.05). The number of coronary artery branches involved and the severity of stenosis differed significantly between patients with consistently high and low apoB/ LDL-C levels (P>0.005). Compared with those with low apoB/low LDL-C levels, the patients with high apoB/ low LDL-C levels showed a significantly greater number of coronary artery branches with lesions (P=0.017) and more severe stenosis (P=0.034), but such differences were not found in patients with low apoB/ high LDL-C levels. Pearson correlation analysis identified LDL-C and apoB as the risk factors for cardiovascular disease with areas under the ROC curve of 0.579 (P= 0.014) and 0.589 (P=0.006), respectively. CONCLUSIONS: In patients with inconsistent levels of apoB and LDL-C, apoB and LDL-C levels are both risk factors of coronary heart disease in close relation with the disease severity. LDL-C and apoB are comparable for their important values in predicting the risk of coronary heart disease.

To study the association of red blood cell distribution width (RDW) and lipoprotein-associated phospholipase A2 (LP-PLA2) with the degree of coronary artery stenosis in patients with coronary artery disease (CAD) and the value of RDW combined with LP-PLA2 detection in accurate evaluation of coronary artery stenosis.A total of 224 patients including 119 non-CAD cases and 105 CAD cases admitted in our hospital between June, 2013 and June, 2014 were enrolled in this study. The patients' baseline clinical data were collected and venous blood samples were obtained for detecting WBC, RDW-CV and LP-PLA2. The Gensini score of the CAD patients was calculated based on coronary angiographic findings.Compared with the non-CAD patients, CAD patients had significantly higher RDW-CV (P=0.009) and LP-PLA2 (P=0.004) levels. The CAD patients with high Gensini scores had also significantly higher RDW-CV (P=0.001) and LP-PLA2 (P0.001) levels than those with low scores; RDW-CV and LP-PLA2 were significantly correlated with the Gensini score, and the area under curve of their combined detection was 0.931.Combination of RDW and LP-PLA2 can improve the diagnostic accuracy of the degree of coronary artery stenosis in patients with CAD.

Purpose: To prepare and characterize buccal transmucosal delivery system of enalapril maleate for overcoming its low bioavailability, and hence provide improved therapeutic efficacy and patient compliance. Methods: Transmucosal drug delivery systems of enalapril maleate were formulated as buccal films by solvent casting technique using polyvinylpyrrolidone K90, hydroxypropyl methylcellulose, sodium carboxymethylcellulose (high viscosity). The films were evaluated for film weight, thickness, folding endurance, drug content uniformity, surface pH, in vitro residence time, in vitro drug release and ex-vivo permeation. Results: All the formulations showed high drug content (96.45 to 98.49 %). Those with good swelling showed good residence time. In vitro drug release was highest for films prepared with high viscosity grade sodium carboxymethylcellulose (SCMC- HV,F2), releasing 92.24 % of drug in 1.5 h) followed by F4 (containing polyvinyl pyrrolidone K-90 1 % w/v and SCMC (HV) 1 % w/v). Ex-vivo drug permeation at the end of 10 h was 82.24 and 89.9 % for F2 and F4, respectively. Conclusion: Prompt drug release was obtained from the formulation (F2) containing SCMC 2 % w/v with 10 mg enalapril. However, on the basis of the highest swelling and residence time, and controlled drug release, formulation F4 (containing PVP K-90 and SCMC HV) would be suitable for the development of buccal film for effective therapy of cardiac diseases. Keywords: Cardiac disease, Transmucosal, Buccal films, Enalapril maleate, Drug release, Ex-vivo permeation

In this study, an energy-efficient, configurable chip that can store and display phone numbers was designed. The chip is incorporated into an alert bracelet that can be used by people with cognitive dysfunction. The bracelet provides an uncomplicated, flexible, operationally safe, and cost-effective method for locating wandering and disoriented people.