Bifunctional hydroformylation on heterogeneous Rh-WOx pair site catalysts.

Metal-catalysed reactions are often hypothesized to proceed on bifunctional active sites, whereby colocalized reactive species facilitate distinct elementary steps in a catalytic cycle1-8. Bifunctional active sites have been established on homogeneous binuclear organometallic catalysts9-11. Empirical evidence exists for bifunctional active sites on supported metal catalysts, for example, at metal-oxide support interfaces2,6,7,12. However, elucidating bifunctional reaction mechanisms on supported metal catalysts is challenging due to the distribution of potential active-site structures, their dynamic reconstruction and required non-mean-field kinetic descriptions7,12,13. We overcome these limitations by synthesizing supported, atomically dispersed rhodium-tungsten oxide (Rh-WOx) pair site catalysts. The relative simplicity of the pair site structure and sufficient description by mean-field modelling enable correlation of the experimental kinetics with first principles-based microkinetic simulations. The Rh-WOx pair sites catalyse ethylene hydroformylation through a bifunctional mechanism involving Rh-assisted WOx reduction, transfer of ethylene from WOx to Rh and H2 dissociation at the Rh-WOx interface. The pair sites exhibited >95% selectivity at a product formation rate of 0.1 gpropanal cm-3 h-1 in gas-phase ethylene hydroformylation. Our results demonstrate that oxide-supported pair sites can enable bifunctional reaction mechanisms with high activity and selectivity for reactions that are performed in industry using homogeneous catalysts.

Phase Engineering of 2D Materials.

Polymorphic 2D materials allow structural and electronic phase engineering, which can be used to realize energy-efficient, cost-effective, and scalable device applications. The phase engineering covers not only conventional structural and metal-insulator transitions but also magnetic states, strongly correlated band structures, and topological phases in rich 2D materials. The methods used for the local phase engineering of 2D materials include various optical, geometrical, and chemical processes as well as traditional thermodynamic approaches. In this Review, we survey the precise manipulation of local phases and phase patterning of 2D materials, particularly with ideal and versatile phase interfaces for electronic and energy device applications. Polymorphic 2D materials and diverse quantum materials with their layered, vertical, and lateral geometries are discussed with an emphasis on the role and use of their phase interfaces. Various phase interfaces have demonstrated superior and unique performance in electronic and energy devices. The phase patterning leads to novel homo- and heterojunction structures of 2D materials with low-dimensional phase boundaries, which highlights their potential for technological breakthroughs in future electronic, quantum, and energy devices. Accordingly, we encourage researchers to investigate and exploit phase patterning in emerging 2D materials.

Uncovering the health implications of abandoned mines through protein profiling of local residents.

Residents in areas with abandoned mines risk significant exposure to abundant heavy metals in the environment. However, current clinical indicators cannot fully reflect the health changes associated with abandoned mine exposure. The aim of this study was to identify biological changes in the residents of abandoned mine areas via proteomic analysis of their blood. Blood samples were collected from abandoned mine and control areas, and mass spectrometry was used for protein profiling. A total of 138 unique or common proteins that were differentially expressed in low-exposure abandoned mine area (LoAMA) or high-exposure abandoned mine area (HiAMA) compared to non-exposure control area (NEA) were analyzed, and identified 4 clusters based on functional similarity. Among the 10 proteins that showed specific change in LoAMA, 4 proteins(Apolipoprotein M, Apolipoprotein E, Apolipoprotein L1, and Cholesteryl ester transfer protein) were cluded in cluster 1(plasma lipoprotein remodeling), and linked to proteins that showed specific change in protein expression in HiAMA. Therefore, it is suggested that 4 proteins are changed at low exposure to an abandoned mine (or initial exposure), and then at high exposure, changes in various proteins involved in linked plasma lipoprotein remodeling are induced, which might triggered by the 4 proteins. Interestingly, in addition to plasma lipoprotein remodeling, proteins involved in other functional networks were changed in the high exposure group. These were all directly or indirectly linked to the 4 biomarkers(Apolipoprotein M, Apolipoprotein E, Apolipoprotein L1, and Cholesteryl ester transfer protein) that changed during low exposure. This suggests their potential utility in identifying areas impacted by abandoned mines. Especially, proteins involved in lipid metabolism and renal function-related diseases in individuals exposed to heavy metals in abandoned mine areas were correlated. Chronic kidney disease is predominantly instigated by cardiovascular disease and is commonly accompanied by dyslipidemia.

Bilateral Visual Impairment following Combination Chemotherapy with Carboplatin in Patients with Small Cell Lung Cancer: A Case Report.

Background: Platinum-based combination chemotherapy, including cisplatin and carboplatin, are important cytotoxic anti-cancer agents that are widely used to treat various solid tumors. Carboplatin has a similar effect on survival in small cell lung cancer, but generally has a milder toxicity profile when compared with cisplatin. Both may cause moderate or severe neurotoxicity, but ocular neurotoxicity from carboplatin is rarely reported. Case presentation: A 79-year-old man underwent intravenous polychemotherapy (atezolizumab, etoposide, and carboplatin) for small cell lung cancer. One week after the second cycle of chemotherapy, he reported bilateral visual loss as hand motion in both eyes. Dilated fundus examination showed retinal arterial narrowing without hemorrhage, and diffuse choroidal and retinal thinning was observed in an optical coherence tomography scan. Fluorescein angiography revealed significantly delayed circulation without evidence of obstructive lesions. 30-Flicker electroretinogram testing showed a complete absence of cone response in both eyes. The patient's visual acuity aggravated to no light perception in both eyes, even after the cessation of chemotherapy. Conclusions: Carboplatin combination chemotherapy administered at therapeutic doses can result in irreversible visual loss, a side effect that is not widely acknowledged. When using carboplatin, physicians should be aware of its potential ocular toxicity.

Discovery and validation of metabolite markers in bloodstains for bloodstain age estimation.

Bloodstain age estimation involves measuring time-dependent changes in the levels of biomolecules in bloodstains. Although several studies have identified bloodstain metabolites as markers for estimating bloodstain age, none have considered sex, age-related metabolomic differences, or long-time bloodstain age. Therefore, we aimed to identify metabolite markers for estimating the age of bloodstains at weekly intervals within 28 days and validate them through multiple reaction monitoring. Adenosine 5'-monophosphate, choline, and pyroglutamic acid were selected as markers. Seven metabolites were validated, including five previously reported metabolites, ergothioneine, hypoxanthine, L-isoleucine, L-tryptophan, and pyroglutamic acid. Choline and hypoxanthine can be used to differentiate bloodstains between days 0 and 14 after deposition at weekly intervals, whereas L-isoleucine and L-tryptophan can help distinguish bloodstains between 7 days before and 14 days after deposition. Evaluation of the changes in metabolite levels according to sex and age revealed that the average levels of all seven metabolites were higher in women on day 0. Moreover, the level of ergothioneine was significantly higher in elderly individuals than in young individuals at all time points. In this study, we confirmed the potential effectiveness of metabolites in bloodstains as forensic markers and provided a new perspective on metabolomic approaches linked to forensic science.

Effect of environmental conditions on bloodstain metabolite analysis.

Establishing a correlation between environmental variables and chemical change can significantly improve the quality of research in multiple fields. Among various environmental variables, temperature and humidity are closely related to the rate of chemical reactions. This study aimed to confirm changes in metabolite markers that were previously discovered in other temperature and humidity environment conditions and to confirm the possibility that they could act as markers. After blood collection from the subjects and bloodstain preparation, the quantitative values of the bloodstain metabolites were confirmed (when the age of the bloodstain was within a month) under eight environmental conditions (4 °C/30%, 4 °C/60%, 25 °C/30%, 25 °C/60%, 25 °C/90%, 40 °C/30%, 40 °C/60%, and 40 °C/90%). Age-of-bloodstain estimation models were constructed to confirm the applicability of bloodstain metabolites as markers for bloodstain age in various environments. The average concentration of metabolite markers exhibited a decreasing trend with the age of the bloodstain, which transformed into an increasing trend from day 7 onwards. In terms of temperature and humidity, 25 °C and 90%, respectively, showed the most dissimilar metabolite change pattern compared to other conditions. The age-of-bloodstain estimation models developed here have an R-square value of up to 0.92 for each condition and an R-square value of 0.71 when all environmental conditions were combined. The findings herein highlight the immense potential of blood metabolites for field application, confirming the possibility of predicting metabolite changes from the rates of their chemical reactions and validating the importance of metabolites as age-of-bloodstain markers under various environmental conditions.

Bloodstain Metabolite Markers: Discovery and Validation for Estimating Age of Bloodstain within 7 Days.

Metabolomic research using analytical chemistry methods has been carried out in a wide range of research fields. However, research combining forensic science and metabolomics is rare. Determining the age of bloodstains could provide key information regarding when a crime was committed. Currently, validated methods for estimating the age of bloodstains are unavailable. Metabolites are intermediate and final products of chemical reactions. Therefore, they are less likely to be degraded than other components of blood under field conditions. In this study, metabolites in bloodstains were analyzed using liquid chromatography-mass spectrometry to discover and validate metabolic markers for determining the age of bloodstains within a week post-bleeding. Nontargeted analysis of bloodstain metabolites revealed statistically significant differences over time. Quantitative analysis of identified candidates via multiple reaction monitoring confirmed the statistical significance according to the age of bloodstain. Pyroglutamic acid, l-glutamine, acetylcarnitine, and adenosine 5'-monophosphate were selected as the final markers. The content of each marker exhibited a statistically significant and consistent tendency to decrease with the age of bloodstain. Furthermore, the effect of hemolysis was considered according to the blood fraction spots of the four markers. This study is the first to identify and validate metabolite markers that may help determine the age of bloodstains within a week post-bleeding. If applied to crime scenes as indicators of the age of bloodstains, they can be used as innovative and important tools for reconstructing crime scenes, suggesting initial investigative direction. This study highlights the forensic utility of blood metabolites ex vivo.

Discovery of donor age markers from bloodstain by LC-MS/MS using a metabolic approach.

Bloodstains are frequently encountered at crime scenes and they provide important evidence about the incident, such as information about the victim or suspect and the time of death or other events. Efforts have been made to identify the age of the bloodstain's donor through genomic approaches, but there are some limitations, such as the availability of databases and the quality dependence of DNA. There is a need for the development of a tool that can obtain information at once from a small blood sample. The aim of this study is to identify bloodstain metabolite candidates that can be used to determine donor age. We prepared bloodstain samples and analyzed metabolites using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Eighteen molecular features (MFs) were selected as candidates using volcano plots and multivariate analysis. Based on the MS/MS spectrum of the MFs, the following nine metabolites were identified from the METaboliteLINk database: Δ2-cis eicosenoic acid, ergothioneine, adenosine 5'-monophosphate, benzaldehyde, phenacylamine, myristic acid ethyl ester, p-coumaric acid, niacinamide, and N-arachidonoyl-L-alanine. These nine age markers at high or low abundances could be used to estimate the age of a bloodstain's donor. This study was the first to develop metabolite age markers that can be used to analyze crime scene bloodstains.

A safe and sustainable bacterial cellulose nanofiber separator for lithium rechargeable batteries.

Bacterial cellulose nanofiber (BCNF) with high thermal stability produced by an ecofriendly process has emerged as a promising solution to realize safe and sustainable materials in the large-scale battery. However, an understanding of the actual thermal behavior of the BCNF in the full-cell battery has been lacking, and the yield is still limited for commercialization. Here, we report the entire process of BCNF production and battery manufacture. We systematically constructed a strain with the highest yield (31.5%) by increasing metabolic flux and improved safety by introducing a Lewis base to overcome thermochemical degradation in the battery. This report will open ways of exploiting the BCNF as a "single-layer" separator, a good alternative to the existing chemical-derived one, and thus can greatly contribute to solving the environmental and safety issues.

Validation of the Metabolite Ergothioneine as a Forensic Marker in Bloodstains.

Ergothioneine, which is a naturally occurring metabolite, generally accumulates in tissues and cells subjected to oxidative stress, owing to its structural stability at physiological pH; therefore, it has been attracting attention in various biomedical fields. Ergothioneine has also been suggested as a potential forensic marker, but its applicability has not yet been quantitatively validated. In this study, quantitative analysis of ergothioneine in bloodstains was conducted to estimate the age of bloodstains and that of bloodstain donors. Blood from youth and elderly participants was used to generate bloodstains. After extracting metabolites from the bloodstains under prevalent age conditions, ergothioneine levels were quantified by mass spectrometry via multiple reaction monitoring. The concentration of ergothioneine in day 0 bloodstains (fresh blood), was significantly higher in the elderly group than in the youth group, but it did not differ by sex. Statistically significant differences were observed between the samples from the two age groups on days 0, 5 and 7, and on days 2 and 3 compared with day 0. The findings suggest that ergothioneine can be used to estimate the age of bloodstains and of the donor; it could be useful as a potential marker in reconstructing crime scenes.

Cancer-associated fibroblasts induce an aggressive phenotypic shift in non-malignant breast epithelial cells via interleukin-8 and S100A8.

Cancer-associated fibroblasts (CAFs) in the tumor microenvironment have been associated with tumor progression in breast cancer. Although crosstalk between breast cancer cells and CAFs has been studied, the effect of CAFs on non-neoplastic breast epithelial cells is not fully understood to date. Here, we investigated the effect of CAFs on aggressive phenotypes in non-neoplastic MCF10A breast epithelial cells. CAFs induced epithelial-to-mesenchymal transition (EMT) and invasive phenotype in MCF10A cells. S100A8, a potential prognostic marker in several cancers, was markedly increased in MCF10A cells by CAFs. S100A8 was crucial for CAFs-induced invasive phenotype of MCF10A cells. Among cytokines increased by CAFs, interleukin (IL)-8 induced S100A8 through transcription factors p65 NF-κB and C/EBPß. In a xenograft mouse model with MCF10A cells and CAFs, tumor was not developed, suggesting that coinjection with CAFs may not be sufficient for in vivo tumorigenicity of MCF10A cells. Xenograft mouse tumor models with MDA-MB-231 breast carcinoma cells provided an in vivo evidence for the effect of CAFs on breast cancer progression as well as a crucial role of IL-8 in tumor growth and S100A8 expression in vivo. Using a tissue microarray of human breast cancer, we showed that S100A8 expression was correlated with poor outcomes. S100A8 expression was more frequently detected in cancer-adjacent normal human breast tissues than in normal breast tissues. Together, this study elucidated a novel mechanism for the acquisition of invasive phenotype of non-neoplastic breast cells induced by CAFs, suggesting that targeting IL-8 and S100A8 may be an effective strategy against breast cancer.

Healthy measures: Feasibility study of a moderate carbohydrate weight management intervention.

BACKGROUND: People of all weights need to prevent changes that could lead to obesity, a leading public health issue. OBJECTIVE: To assess the feasibility of Healthy Measures, a moderate carbohydrate (160-300 g/d) nutrition education and behavioral intervention. DESIGN: An uncontrolled intervention feasibility study including in-person group meetings every 2 weeks for 3 months. SAMPLE: Fifteen participants of normal and overweight BMI. MEASUREMENTS: We assessed feasibility of recruitment, attendance, retention and satisfaction as well as anthropometric measures and social cognitive variables with Healthy Measures, a nutrition-focused intervention with moderate carbohydrate portions that also emphasizes self-monitoring of anthropometric measurements. An intent-to-treat analysis was used. RESULTS: Healthy Measures was feasible, with 13 participants (86.7%) completing pre- and post-intervention assessments. Eight participants lost or maintained weight (53.3%); four gained weight. Healthy eating self-efficacy increased overall (t = -2.54, p = .024). Increased protein and fat intake was associated with weight loss, while reduced protein, carbohydrate, and fat intake resulted in weight gain. CONCLUSIONS: Healthy Measures shows promise for prevention of weight gain, with evidence of feasibility and positive outcomes. Further research is needed to establish efficacy relative to alternative approaches.

Metabolomic profiling of bloodstains on various absorbent and non-absorbent surfaces.

Bloodstains found at crime scenes contain immense information about the crime; thus, studies involving analysis of small molecules in bloodstains have been conducted. However, most of these studies have not accounted for the difference in the results of small molecule analysis due to the surface of bloodstains. To evaluate the "surface effect," we prepared bloodstains on seven surfaces, including both absorbent and non-absorbent surfaces, and performed global small molecule analysis by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). We used three indicators: (1) count recovery rate (%) of molecular features (MFs), (2) the number of MFs extracted from the surface without bloodstains, and (3) difference in abundance recovery rate (%) of MFs, to determine the ranking of the seven surfaces in the order of their similarity with blood. We also confirmed the correlation between each surface and blood through multivariate analysis. We found that the non-absorbent surfaces ranked better than the absorbent surfaces; wooden flooring was ranked as the most efficient surface, followed by stainless, vinyl flooring, glass, tile, filter paper, and mixed cotton. This study will help in the selection of the most efficient surface for collection of bloodstains for small molecule analysis from a crime scene. This is the first study to identify the effects of surface on extraction of global small molecules from bloodstains; it will help forensic scientists in obtaining more accurate information from small molecules present in the bloodstains collected at the field. Graphical abstract.

Thymosin ß4 Reduces H2O2 Induced Oxidative Stress in MC3T3-E1 Cells on Titanium Surface.

Thymosin ß4 (Tß4) is known to inhibit an inflammatory response and to increase the survival of osteoblasts on titanium (Ti) surfaces. Ti is the most widely used graft material in dentistry; however, an inflammatory response induced following implant placement results in the generation of reactive oxygen species (ROS). The oxidative stress from the production of ROS such as nitric oxide (NO) and hydrogen peroxide (H2O2) can damage surrounding cells, resulting in implant failure by decreasing cell viability. Thus, the aim of this study was to determine the biological effects of Tß4 on the oxidative stress induced to MC3T3-E1 preosteoblasts on the Ti surface. Based on an MTT assay and bromodeoxyuridine immunofluorescence staining, Tß4 was found to increase the proliferation of the H2O2-exposed MC3T3-E1 cells on Ti discs. Reverse transcription-polymerase chain reaction and western blot analyses showed that Tß4 decreased the mRNA and protein expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in H2O2-exposed MC3T3-E1 cells on the Ti discs. Tß4 inhibited the synthesis of intracellular ROS and the secretion of NO and prostaglandin E2 (PGE2) from H2O2-exposed MC3T3-E1 cells on the Ti discs. In conclusion, Tß4 inhibits H2O2-induced iNOS and COX-2 expression with a decrease in ROS, NO, and PGE2 synthesis, which leads to improved cell survival with low cytotoxicity under an oxidative stress condition in MC3T3-E1 cells on the Ti surface. This suggests that Tß4 may be a crucial molecule to reduce oxidative stress-induced cell damage or hypoxia, leading to promoted osseointegration on the Ti surface during implant placement.

Efficient Syntheses of 1,2,3-Triazoloamide Derivatives Using Solid- and Solution-Phase Synthetic Approaches.

Efficient synthetic routes for the preparation of secondary and tertiary 1,2,3-triazoloamide derivatives were developed. A secondary α-1,2,3-triazoloamide library was constructed and expanded by a previously developed solid-phase synthetic route and a tertiary 1,2,3-triazoloamide library was constructed by a parallel solution-phase synthetic route. The synthetic routes rely on amide formation with secondary amines and chloro-acid chlorides; SN2 reaction with sodium azide; and the selective [3 + 2] Hüisgen cycloaddition with appropriate terminal alkynes. The target secondary and tertiary 1,2,3-triazoloamide derivatives were obtained with three-diversity points in excellent overall yields and purities using the reported solid- and solution-phase synthetic routes, respectively.

Social capital, social support, and food insecurity in food pantry users.

The purpose of this study was to examine the relationship between food security, social capital, and social support among urban food pantry users in Cincinnati. In-person interviews with 53 participants were completed using the U.S. Household Food Security Survey Module, Social Capital questionnaire, and Social Support questionnaire. Social capital was assessed through four subscales using a Likert scale, with a response range 1 to 4, and social support was measured by rating significant others' emotional, informational, and instrumental support as well as companionship (ranged from 0 to 4). The findings suggested that there were no significant associations among them. This may be due to a small sample size. Thus, the associations need to be examined with a larger sample. Further, a qualitative approach may be necessary to explore the contextual nature of social capital and social support related to food security.

Discovery and validation of protein biomarkers for monitoring the effectiveness of drug treatment for major depressive disorder.

Major depressive disorder (MDD) has a high prevalence worldwide. Although the economic burden of depression increases annually, the proportion of patients with MDD receiving treatment did not increase between 2010 and 2018, suggesting an unmet treatment need. The burden of long-term treatment for depression is borne by patients. In this context, biomarkers associated with drug-treatment responses can be used as reference indicators to reduce unnecessary treatment and costs. Changes in biomolecules in response to drug treatment for depression and drug-treatment response markers have been studied extensively. The Hamilton Depression Rating Scale (HAM-D) is mainly used as an indicator of response and remission; however, it is difficult to determine whether the medication contributes to recovery when evaluating the effect of drug treatment for depression based on this assessment. Therefore, it is necessary to monitor the effect of medication compared to normal health conditions. Here, serum protein levels were compared using liquid chromatography-tandem mass spectrometry among a group of patients with depression who did not receive medication, a group of patients receiving medication, and a control group. Eight selected biomarkers, including Apolipoproteins A-I, Complement factor H, Complement C5, Complement C1q subcomponent subunit B, Alpha-2-HS-glycoprotein, Complement C1q subcomponent subunit C, Vitamin D-binding protein and Corticosteroid-binding globulin were distinguished between disease states, and protein levels in the drug-treated group were similar to those in the control group. These markers can be used to monitor the effectiveness of drug treatment.

Epoxy-Based Copper (Cu) Sintering Pastes for Enhanced Bonding Strength and Preventing Cu Oxidation after Sintering.

The investigation of interconnection technologies is crucial for advancing semiconductor packaging technology. This study delved into the various methods of achieving electrical interconnections, focusing on the sintering process and composition of the epoxy. Although silver (Ag) has traditionally been utilized in the sintering process, its high cost often precludes widespread commercial applications. Copper (Cu) is a promising alternative that offers advantages, such as cost-effectiveness and high thermal and electrical conductivities. However, the mechanical robustness of the oxide layers formed on Cu surfaces results in several challenges. This research addresses these challenges by integrating epoxy, which has advantages such as adhesive capabilities, chemical resistance, and robust mechanical properties. The chemical reactivity of the epoxy was harnessed to both fortify adhesion and inhibit oxide layer formation. However, the optimal sintering performance required considering both the composite composition (20 wt% epoxy) and the specific sintering conditions (pre-heating at 200 °C and sintering at 250 °C). The experimental findings reveal a balance in the incorporation of epoxy (20 wt%) for the desired electrical and mechanical properties. In particular, the bisphenol A epoxy (Da)-containing sintered Cu chip exhibited the highest lab shear strength (35.9 MPa), whereas the sintered Cu chip without epoxy represented the lowest lab shear strength of 2.7 MPa. Additionally, the introduction of epoxy effectively curtailed the onset of oxidation in the sintered Cu chips, further enhancing their durability. For instance, 30 days after sintering, the percentage of oxygen atoms in the Da-containing sintered Cu chip (4.5%) was significantly lower than that in the sintered Cu chip without epoxy (37.6%), emphasizing the role of epoxy in improving Cu oxidation resistance. Similarly, the samples sintered with bisphenol-based epoxy binders exhibited the highest electrical and thermal conductivities after 1 month. This study provides insights into interactions between epoxy, carboxylic acid, solvents, and Cu during sintering and offers a foundation for refining the sintering conditions.

Simulation and Controller Design for a Fish Robot with Control Fins.

In this paper, a nonlinear simulation block for a fish robot was designed using MATLAB Simulink. The simulation block incorporated added masses, hydrodynamic damping forces, restoring forces, and forces and moments due to dorsal fins, pectoral fins, and caudal fins into six-degree-of-freedom equations of motion. To obtain a linearized model, we used three different nominal surge velocities (i.e., 0.2 m/s, 0.4 m/s, and 0.6 m/s). After obtaining output responses by applying pseudo-random binary signal inputs to a nonlinear model, an identification tool was used to obtain approximated linear models between inputs and outputs. Utilizing the obtained linearized models, two-degree-of-freedom proportional, integral, and derivative controllers were designed, and their characteristics were analyzed. For the 0.4 m/s nominal surge velocity models, the gain margins and phase margins of the surge, pitch, and yaw controllers were infinity and 69 degrees, 26.3 dB and 85 degrees, and infinity and 69 degrees, respectively. The bandwidths of surge, pitch, and yaw control loops were determined to be 2.3 rad/s, 0.17 rad/s, and 2.0 rad/s, respectively. Similar characteristics were observed when controllers designed for linear models were applied to the nonlinear model. When step inputs were applied to the nonlinear model, the maximum overshoot and steady-state errors were very small. It was also found that the nonlinear plant with three different nominal surge velocities could be controlled by a single controller designed for a linear model with a nominal surge velocity of 0.4 m/s. Therefore, controllers designed using linear approximation models are expected to work well with an actual nonlinear model.

Association between age-related macular degeneration and risk of incident cancer.

BACKGROUND/AIMS: Age-related macular degeneration (AMD) and cancer may share similar risk factors, indicating possible common pathogenic pathways. We aimed to describe the site-specific cancer risk based on the relationship of AMD with visual disability (VD) status. METHODS: This was a population-based cohort study using data from the Korean National Health Insurance Service database (2009-2019) including patients who participated in a national health screening programme in 2009. The subjects were categorised based on the presence of AMD and VD. The occurrence of cancer was identified using principal diagnosis according to the International Classification of Disease, 10th revision codes in claims data. The Cox regression hazard model was used to compare HRs of site-specific cancer. RESULTS: Among 4 088 814 participants, 51 596 had AMD of which 3683 subjects had VD. The mean follow-up period was 9.6 years. The overall cancer risk was generally null, but the risk of hypervascular cancer such as thyroid cancer (adjusted HR (aHR) 1.10, 95% CI 1.00 to 1.20) and renal cancer (aHR 1.16, 95% CI 1.00 to 1.33) was higher and the risk of stomach cancer (aHR 0.89, 95% CI 0.84 to 0.94) was lower in the AMD group than in the non-AMD group. CONCLUSION: This study demonstrated a possible association between AMD and several cancers. Increased renal and thyroid cancer risk among patients with AMD could indicate that AMD is associated with hypervascular cancer. Further studies in which additional databases are used and the underlying detailed mechanisms evaluated are needed to validate our results.