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A low-profile wideband circularly polarized (CP) metasurface antenna is demonstrated for C-band applications. The metasurface consists of 4 × 4 square patches with Z-shaped slots. Characteristic mode analysis is used to investigate the modal behavior of the metasurface, and a pair of degenerate modes is chosen as the operating modes. The CP radiation is realized by exciting a pair of degenerate modes of the metasurface through a slot antenna, which is used as a feed structure with a 90° phase difference. The CP bandwidth is further widened by combining the resonance modes of the metasurface and slot antenna. The measured results show that the −10 dB impedance bandwidth of the antenna is 3.47–4.76 GHz, and the 3 dB axial ratio bandwidth is 3.5–4.9 GHz with a peak gain of 6.9 dBic. Moreover, the antenna exhibits well left-hand CP radiation performances with a low profile of 0.046λ0.
Catecholaminergic polymorphic ventricular tachycardia is an ion channelopathy, caused by mutations in genes coding for calcium-handling proteins. It can coexist with left ventricular non-compaction. We aim to investigate the clinical and genetic characteristics of this co-phenotype.
Medical records of 24 patients diagnosed with catecholaminergic polymorphic ventricular tachycardia in two Chinese hospitals between September, 2005, and January, 2020, were retrospectively reviewed. We evaluated their clinical and genetic characteristics, including basic demographic data, electrocardiogram parameters, medications and survival during follow-up, and their gene mutations. We did structural analysis for a novel variant ryanodine receptor 2-E4005V.
The patients included 19 with catecholaminergic polymorphic ventricular tachycardia mono-phenotype and 5 catecholaminergic polymorphic ventricular tachycardia-left ventricular non-compaction overlap patients. The median age of onset symptoms was 9.0 (8.0,13.5) years. Most patients (91.7%) had cardiac symptoms, and 50% had a family history of syncope. Overlap patients had lower peak heart rate and threshold heart rate for ventricular tachycardia and ventricular premature beat during the exercise stress test (p < 0.05). Sudden cardiac death risk may be higher in overlap patients during follow-up. Gene sequencing revealed 1 novel ryanodine receptor 2 missense mutation E4005V and 1 mutation previously unreported in catecholaminergic polymorphic ventricular tachycardia, but no left ventricular non-compaction-causing mutations were observed. In-silico analysis showed the novel mutation E4005V broke down the interaction between two charged residues.
Catecholaminergic polymorphic ventricular tachycardia overlapping with left ventricular non-compaction may lead to ventricular premature beat/ventricular tachycardia during exercise stress test at lower threshold heart rate than catecholaminergic polymorphic ventricular tachycardia alone; it may also indicate a worse prognosis and requires strict follow-up. ryanodine receptor 2 mutations disrupted interactions between residues and may interfere the function of ryanodine receptor 2.
OBJECTIVES/GOALS: Single-cell and spatial transcriptomics have revealed high heterogeneity in the tumor and microenvironment. Identifying populations of cells that impact a patient’s prognosis is an important research goal, so researchers can generate hypotheses and clinicians can provide targeted treatment. METHODS/STUDY POPULATION: DEGAS uses deep-transfer-learning to identify patterns between patient tumor RNA-seq and clinical outcomes and map these associations on to higher-resolution data like spatial and single-cell transcriptomics. We apply DEGAS to prostate and pancreatic cancer spatial transcriptomics samples, as well as one normal sample of prostate tissue. We used the TCGA prostate cancer cohort to with the accompanying survival information and publicly accessible prostate cancer ST data from 10X Genomics to predict survival associations in the ST slides derived from the TCGA patients. Based on these survival associations, we identify higher risk subsections of ST slides which can be further studied. RESULTS/ANTICIPATED RESULTS: We were able to validate our method by comparing it to Scissor and were able to show that the number of high-risk regions in prostate cancer slides increased with the stage of disease. Furthermore, we identify transcriptomic signatures enriched for ontology terms associated with growth regulation and apoptosis, inflammation, immune signaling, and autophagy in histologically normal prostate tissues and adjacent normal pancreatic cancer tissues that were identified as high-risk by DEGAS. The regions highlighted by DEGAS could reflect transcriptional precursors to intraepithelial neoplasia–a well-recognized premalignant morphological change in glandular epithelium. DISCUSSION/SIGNIFICANCE: Identifying biomarkers of tissue stress that precede morphologic diagnosis of high-grade pre-malignant lesions by a pathologist may help triage patients at high risk for future development of cancer, or aid in better understanding whether histologically normal pre-malignant tissues at tumor margins contribute to recurrence.
Multilayer dielectric gratings typically remove multiple-grating pillars after picosecond laser irradiation; however, the dynamic formation process of the removal is still unclear. In this study, the damage morphologies of multilayer dielectric gratings induced by an 8.6-ps laser pulse were closely examined. The damage included the removal of a single grating pillar and consecutive adjacent grating pillars and did not involve the destruction of the internal high-reflection mirror structure. Comparative analysis of the two damage morphological characteristics indicated the removal of adjacent pillars was related to an impact process caused by the eruption of localized materials from the left-hand pillar, exerting impact pressure on its adjacent pillars and eventually resulting in multiple pillar removal. A finite-element strain model was used to calculate the stress distribution of the grating after impact. According to the electric field distribution, the eruptive pressure of the dielectric materials after ionization was also simulated. The results suggest that the eruptive pressure resulted in a stress concentration at the root of the adjacent pillar that was sufficient to cause damage, corresponding to the experimental removal of the adjacent pillar from the root. This study provides further understanding of the laser-induced damage behavior of grating pillars and some insights into reducing the undesirable damage process for practical applications.
The mitochondrial genome provides important information for phylogenetic analysis and an understanding of evolutionary origin. In this study, the mitochondrial genomes of Ilisha elongata and Setipinna tenuifilis were sequenced, which are typical circular vertebrate mitochondrial genomes composed of 16,770 and 16,805 bp, respectively. The mitogenomes of I. elongata and S. tenuifilis include 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA), two ribosomal RNA (rRNA) genes and one control region (CR). Both two species' genome compositions were highly A + T biased and exhibited positive AT-skews and negative GC-skews. The genetic distance and Ka/Ks ratio analyses indicated that 13 PCGs were affected by purifying selection and the selection pressures were different from certain deep-sea fishes, which were most likely due to the difference in their living environment. Results of phylogenetic analysis support close relationships among Chirocentridae, Denticipitidae, Clupeidae, Engraulidae and Pristigasteridae based on the nucleotide and amino acid sequences of 13 PCGs. Within Clupeoidei, I. elongata and S. tenuifilis were most closely related to the family Pristigasteridae and Engraulidae, respectively. These results will help to better understand the evolutionary position of Clupeiformes and provide a reference for further phylogenetic research on Clupeiformes species.
It has been suggested that added sugar intake is associated with non-alcoholic fatty liver disease (NAFLD). However, previous studies only focused on sugar-sweetened beverages; the evidence for associations with total added sugars and their sources is scarce. This study aimed to examine the associations of total added sugars, their physical forms (liquid v. solid) and food sources with risk of NAFLD among adults in Tianjin, China. We used data from 15 538 participants, free of NAFLD, other liver diseases, CVD, cancer or diabetes at baseline (2013–2018 years). Added sugar intake was estimated from a validated 100-item FFQ. NAFLD was diagnosed by ultrasonography after exclusion of other causes of liver diseases. Multivariable Cox proportional hazards models were fitted to calculate hazard ratios (HR) and corresponding 95 % CI for NAFLD risk with added sugar intake. During a median follow-up of 4·2 years, 3476 incident NAFLD cases were documented. After adjusting for age, sex, BMI and its change from baseline to follow-up, lifestyle factors, personal and family medical history and overall diet quality, the multivariable HR of NAFLD risk were 1·18 (95 % CI 1·06, 1·32) for total added sugars, 1·20 (95 % CI 1·08, 1·33) for liquid added sugars and 0·96 (95 % CI 0·86, 1·07) for solid added sugars when comparing the highest quartiles of intake with the lowest quartiles of intake. In this prospective cohort of Chinese adults, higher intakes of total added sugars and liquid added sugars, but not solid added sugars, were associated with a higher risk of NAFLD.
This work studies the detachment of a micron-sized spherical particle from a surface with concave roughness in a linear shear flow. The concave roughness is described as regularly spaced hollow hemispheres below a flat surface and is characterised by two dimensionless parameters, i.e. dimensionless asperity distance and asperity size ratio. The hydrodynamic force and torque on the particle are calculated by performing lattice Boltzmann simulations for particle Reynolds numbers ranging from 0.02 to 40. Empirical correlations of the drag, lift and torque coefficients of the particle as functions of the particle Reynolds number and the asperity size ratio are proposed. For detachment by lifting, sliding and rolling, a numerical approach to calculate the critical particle Reynolds number (i.e. above which the particle can detach from the surface) is proposed. It is found that the dimensionless asperity distance and the distribution of asperities on the rough surface have a minor influence on the hydrodynamic force and torque on the particle, and the detachment of the particle becomes more difficult as the particle sits deeper in a larger hole. Both the empirical correlations and the numerical approach can be implemented into Lagrangian particle tracking and can accurately predict the detachment of particles from the surface with concave roughness or the detachment of particles embedded in a flat surface.
The nutritional status experienced in the early development of life plays a vital role in the long-term metabolic state of the individual, which is known as nutritional programming. The present study investigated the long-term effects of vegetable oil (VO) nutritional programming during the early life of large yellow croaker. First, larvae were fed either a fish oil (FO) diet or a VO diet for 30 d. Subsequently, under the same conditions, all fish were fed a commercial diet for 90 d and thereafter challenged with an FO or VO diet for 30 d. The results showed that growth performance was significantly lower in larvae fed the VO diet than in those in fed the FO diet in the stimulus phase. Notably, VO nutritional history fish showed lower levels of liver lipids liver total triglycerides and serum nonesterified free fatty acids than the FO nutritional history fish when juveniles were challenged with the VO diet, which was consistent with the expression of lipogenesis-related genes and proteins. Moreover, the VO nutritional history fish showed lower liver damage and higher antioxidant capacity than FO nutritional history fish when challenged with the VO diet. In summary, this study showed that a short VO stimulus during the early life stage of large yellow croaker, had a long-term effect on lipid metabolism and the antioxidant system. Specifically, VO nutritional programming had a positive effect on alleviating abnormal lipid deposition on the liver, liver damage, and the reduction of hepatic antioxidant capacity caused by a VO diet.
Prospective cohort studies linking organ meat consumption and non-alcoholic fatty liver disease (NAFLD) are limited, especially in Asian populations. This study aimed to prospectively investigate the association between organ meat consumption and risk of NAFLD in a general Chinese adult population. This prospective cohort study included a total of 15 568 adults who were free of liver disease, CVD and cancer at baseline. Dietary information was collected at baseline using a validated FFQ. NAFLD was diagnosed by abdominal ultrasound after excluding other causes related to chronic liver disease. Cox proportional regression models were used to assess the association between organ meat consumption and risk of NAFLD. During a median of 4·2 years of follow-up, we identified 3604 incident NAFLD cases. After adjusting for demographic characteristics, lifestyle factors, vegetable, fruit, soft drink, seafood and red meat consumption, the multivariable hazard ratios (95 % CI) for incident NAFLD across consumption of organ meat were 1·00 (reference) for almost never, 1·04 (0·94, 1·15) for tertile 1, 1·08 (0·99, 1·19) for tertile 2 and 1·11 (1·01, 1·22) for tertile 3, respectively (Pfor trend < 0·05). Such association did not differ substantially in the sensitivity analysis. Our study indicates that organ meat consumption was related to a modestly higher risk of NAFLD among Chinese adults. Further investigations are needed to confirm this finding.
High dietary fibre intake has been associated with a lower risk of diabetes, but the association of dietary fibre with prediabetes is only speculative, especially in China, where the supportive data from prospective studies are lacking. This study aimed to examine the association between dietary fibre intake and risk of incident prediabetes among Chinese adults. We performed a prospective analysis in 18 085 participants of the Tianjin Chronic Low-grade Systemic Inflammation and Health cohort study who were free of diabetes, prediabetes, cancer and CVD at baseline. Dietary data were collected using a validated 100-item FFQ. Prediabetes was defined based on the American Diabetes Association diagnostic criteria. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95 % CI. During 63 175 person-years of follow-up, 4139 cases of incident prediabetes occurred. The multivariable HR of prediabetes for the highest v. lowest quartiles were 0·85 (95 % CI 0·75, 0·98) (P for trend = 0·02) for total dietary fibre, 0·84 (95 % CI 0·74, 0·95) (P for trend < 0·01) for soluble fibre and 1·05 (95 % CI 0·93, 1·19) (P for trend = 0·38) for insoluble fibre. Fibre from fruits but not from cereals, beans and vegetables was inversely associated with prediabetes. Our results indicate that intakes of total dietary fibre, soluble fibre and fibre derived from fruit sources were associated with a lower risk of prediabetes.
To assess the relationship between the neutrophil-to-lymphocyte ratio (NLR) and related parameters to the severity of coronavirus disease 2019 (COVID-19) symptoms. Clinical data from 38 COVID-19 patients who were diagnosed, treated and discharged from the Qishan Hospital in Yantai over the period from January to February 2020 were analysed. NLR and procalcitonin (PCT) were determined in the first and fourth weeks after their admission, along with the clinical characteristics and laboratory test results of these patients. Based on results as obtained on the first and fourth weeks after admission, five indices consisting of NLR, white blood cells, neutrophils, lymphocytes (LY) and monocytes (MON) were selected to generate receiver operating characteristic curves, while optimal cutoff values, sensitivities and specificities were obtained according to the Yuden index. Statistically significant differences in neutrophils, LY and the NLR were present in the severe vs. moderate COVID-19 group from the first to the fourth week of their hospitalisation. The cut-off value of NLR for predicting the severity of COVID-19 was 4.425, with a sensitivity of 0.855 and a specificity of 0.979. A statistically significant positive correlation was present between PCT and NLR in the severe group as determined within the first week of admission. NLR can serve as a predictor of COVID-19 disease severity as patients' progress from the first to the fourth week of their hospitalisation. The statistically significant positive correlation between levels of NLR and PCT in severe patients indicated that increases in NLR were accompanied with gradual increases in PCT.
Seaweeds have numerous biologically active ingredients, such as polysaccharides, polyphenols and carotenoids, that are beneficial to human health. Although these benefits might be related to the synthesis, secretion or reabsorption of uric acid, no studies have explored the relationship between seaweeds consumption and hyperuricaemia (HUA) in the general population. The aim of this study was to investigate whether seaweeds consumption is related to HUA in a large-scale adult population. A cross-sectional study was conducted with 32 365 adults (17 328 men and 15 037 women) in Tianjin, People’s Republic of China. Frequency of seaweeds consumption was assessed by a validated self-administered FFQ. HUA was defined as serum uric acid levels >420 μmol/L in men and >350 μmol/L in women. The association between seaweeds consumption and HUA was assessed by multiple logistic regression analysis. Restricted cubic spline functions were used for non-linearity tests. The prevalence of HUA in men and women was 21·17 % and 5·93 %, respectively. After adjustments for potential confounding factors, the OR (95 % CI) for HUA across seaweed consumption (g/1000 kcal per d) were 1·00 (reference) for level 1, 0·91 (95 % CI 0·81, 1·02) for level 2; 0·90 (95 % CI 0·81, 1·01) for level 3; 0·86 (95 % CI 0·78, 0·97) for level 4 in men and 0·90 (95 % CI 0·73, 1·10) for level 2; 0·82 (95 % CI 0·67, 1·00) for level 3; 0·84 (95 % CI 0·68, 1·03) for level 4 in women, respectively. A negative correlation between seaweeds consumption and HUA in males but not in females was observed. Further studies are needed to explore the causal relationship.
According to the World Health Organization, there were approximately 0.5 million new cases of rifampicin-resistant tuberculosis in 2018, of which 78 percent were multidrug-resistant tuberculosis (MDR-TB), and China has one of the largest shares of the global burden (14%). In recent years, the Chinese government has made progress in TB control and prevention, but for MDR-TB, treatment options are still limited and expensive, and novel drugs are not always available. This research aims to evaluate the cost-effectiveness of adding bedaquiline to a background regimen (BR) of drugs for MDR-TB treatment in China, and to provide evidence for government to improve public health policies.
A cohort-based Markov model was developed to evaluate the incremental cost-effectiveness ratio (ICER) of bedaquiline plus BR (BBR) versus BR alone in MDR-TB treatment, over a 10-year time horizon. Data were sourced from a phase II clinical trial, real-world data in China, published literature, and expert opinion. Outcomes were evaluated in quality-adjusted life years (QALYs) and life-years gained (LYG). The discount rate was 3.5%. Probabilistic and deterministic sensitivity analyses were conducted.
The discounted costs per person for BBR was CNY 135,706 [USD 19,172], compared with CNY 92,465 [USD 13,063] for BR. The discounted utility per person for BBR was also higher than that for BR (3.943 QALYs versus 3.193 QALYs). The ICER of BBR was CNY 58,096 [USD 8,208]/QALY, which was lower than the willingness-to-pay threshold of CNY 212,676 [USD 30,046] (three-times the gross domestic product per capita). Therefore, BBR was considered to be cost-effective. The sensitivity analysis confirmed the robustness of the results. BBR remained cost-effective in the sensitivity analysis, with a 77.2 percent probability of being cost-effective versus BR.
In China, bedaquiline is not included in the National Reimbursement Medicine List, which results in a heavy financial burden for MDR-TB patients. From this study, BBR was cost-effective by significantly reducing time to sputum culture conversion and increasing QALYs and LYGs, which offset the higher drug costs.
Malignant tumors have become a major public health problem and their treatment cost is increasing rapidly in China, but treatment aimed at healing diseases or extending patients’ life. There is little empirical research on utilization of healthcare resources of terminally ill cancer patients. In order to explore the optimal treatment decision for patients and provide information for relevant decision makers, this study analyzed the consumption status of medical resources in patients with cancer during the whole treatment period, and the current medical resource utilization efficiency in different levels of hospital for end-stage cancer patients.
This study was based on the clinical treatment and payment data of 2,536 cases of patients with lung cancer from the medical insurance database during the period of 2007 to 2014 in Hubei province. We retrospectively analyzed patients’ medical expenditure and utilization of different medical resources during their whole treatment period as well as at the end stage.
The per capita inpatient expenditures of patients under 50 years old was 193,000 CNY (27,451 USD), while that of the patients over 70 years were 80,000–90,000 CNY (11,379–12,802 USD). Secondly, the medical expenditures spent during the last 6 months of life accounted for 66.1 percent of the total expenditures. Lastly, the medical expenditure spent in tertiary hospitals accounted for 95.3 percent of the total expenditure, and the expenditure was 14,200 ± 17,030 CNY (2,019.82 ± 2,422.36 USD) per visit.
Population aging is not the only factor causing the rise of medical expenditure. The unclear objectives of treatment and the reverse of medical resource allocation are also important factors to boost the growth of medical expenditure. It is necessary to improve the healthcare insurance payment system, strengthen the capacity of primary medical institutions, and develop the palliative care system in China.
Since the 18th National Congress of the Communist Party of China (CPC), remarkable achievements have been made in poverty alleviation. Over the past five years, the population of people living in poverty had decreased by 68.53million, fallen from 98.99 million in 2012 to 30.46 million at the end of 2017. As an impoverished province, Hebei province has been implementing the CPC Central Committee's guidance in the battle against poverty. In 2016, the government released the Implementation Scheme Plan for Improving the Level of Medical Security and Assistance. The plan introduces multi-layer medical security and assistance mechanisms which covers basic medical insurance, major disease insurance and medical assistance. In 2017, the government formulated the Implementation Plan for the Three-Batch Action Plan on the Health Care Program for Poverty Alleviation in Hebei Province, for people with major disease. Hebei Province has carried out many explorations on the health care program for poverty alleviation, and its effectiveness is a problem worthy of attention.
Based on data including basic medical insurance, major illness insurance, medical assistance, and other related information, we used descriptive statistics and quantitative methods to evaluate the overall expenditure of the poverty alleviation for Hebei province and the areas under its jurisdiction. Additionally, the expenditure of different levels of medical security system, the medical burden for people facing poverty and the distribution of disease in the population with assistance were evaluated.
The out-of-pocket payment per capita has decreased year by year, and it has dropped to 3% of catastrophic medical expenditure and 20% below the poverty line by June 2018. An imbalanced situation occurred with the implementation, with the more impoverished areas having greater the pressure on medical care and poverty alleviation. For people with medical assistance, diseases with higher population and overall expenditure are cerebrovascular disease, malignant tumor, diabetes and some other chronic diseases.
The health policies for poverty alleviation in Hebei province has achieved a remarkable success, and the medical burden of the poor has been significantly reduced. However, the implementation of the policies in various cities has shown an imbalanced situation, and the poverty alleviation policies need to be further improved.
The study of enclaves in granitic plutons provides fundamental information on the petrogenesis of their host rocks. Here we combine U–Pb zircon ages, petrography, geochemistry and Nd–Hf isotope composition to investigate the origin of dioritic–granodioritic enclaves and their host granodiorites and biotite granites in the Xuehuading–Panshanchong area, which is a pivotal site to study the Palaeozoic intracontinental orogenic processes of the South China Block. Obtained ages indicate that the host rocks were formed in early Silurian time (c. 432 Ma). The enclaves are fine grained, but with mineral assemblages similar to their hosts and contain amphibole, biotite and plagioclase. All rocks have fractionated rare earth element patterns ((La/Yb)N = 2.86–8.16), except for one biotite granite that has a concave rare earth element pattern ((La/Yb)N = 1.50). Most rocks are depleted in Ta–Nb–Ti, and have negative Eu anomalies and ϵNd(t) (–8.86 to –5.75) and zircon ϵHf(t) (–13.30 to –4.11, except for one, –39.08). We interpret that the enclaves were formed at the borders of magma-ascending conduits, where the mafic mineral crystallization was enhanced by rapid cooling. Conversely, the biotite granites were produced by fractional crystallization from a related granodiorite magma. The sample with a concave rare earth element pattern may have been influenced by hydrothermal fluid–melt interaction. Geochemical modelling suggests that the granodiorites were likely generated by disequilibrium melting of heterogeneous amphibolites in the middle–lower crust. Considering the geological data for the Palaeozoic magmatic rocks in the South China Block, we propose that the Xuehuading–Panshanchong magmatism was likely triggered by piecemeal removal of the thickened lithospheric root and subsequent thermal upwelling of mantle, without a mantle-derived magma contribution to the granites.
The upsurge in the number of people affected by the COVID-19 is likely to lead to increased rates of emotional trauma and mental illnesses. This article systematically reviewed the available data on the benefits of interventions to reduce adverse mental health sequelae of infectious disease outbreaks, and to offer guidance for mental health service responses to infectious disease pandemic. PubMed, Web of Science, Embase, PsycINFO, WHO Global Research Database on infectious disease, and the preprint server medRxiv were searched. Of 4278 reports identified, 32 were included in this review. Most articles of psychological interventions were implemented to address the impact of COVID-19 pandemic, followed by Ebola, SARS, and MERS for multiple vulnerable populations. Increasing mental health literacy of the public is vital to prevent the mental health crisis under the COVID-19 pandemic. Group-based cognitive behavioral therapy, psychological first aid, community-based psychosocial arts program, and other culturally adapted interventions were reported as being effective against the mental health impacts of COVID-19, Ebola, and SARS. Culturally-adapted, cost-effective, and accessible strategies integrated into the public health emergency response and established medical systems at the local and national levels are likely to be an effective option to enhance mental health response capacity for the current and for future infectious disease outbreaks. Tele-mental healthcare services were key central components of stepped care for both infectious disease outbreak management and routine support; however, the usefulness and limitations of remote health delivery should also be recognized.
Solid solution 0.94Na0.5Bi0.5TiO3–6BaTiO3 (NBT–6BT) is considered to be one kind of lead-free piezoelectric materials with excellent electrical properties due to the existence of morphotropic phase boundary (MPB). However, its relatively lower depolarization temperature is a long-standing bottleneck for the application of NBT-based piezoelectric ceramics. In this work, the influence of thermal quenching on depolarization temperature and electrical properties of rare-earth Ho-doped NBT–6BT lead-free ceramics was investigated. It was shown that the relative high piezoelectric performance, as well as an improvement of depolarization temperature (Td), can be realized by thermal quenching. The results showed that the quenching process induced high concentration of oxygen vacancy, giving rise to the change of octahedra mode and enhanced lattice distortion, which is benefit to the temperature stability of piezoelectric and ferroelectric properties. Furthermore, up-conversion photoluminescence (PL) of Ho-doped NBT–6BT could be effectively tuned by the introduction of oxygen vacancy, suggesting a promising potential in optical–electrical multifunctional devices.