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Sensitive mid‐infrared (MIR) spectroscopy is highly demanded in various fields ranging from industrial inspection, biomedical diagnosis to astronomical observation. However, the detection sensitivity of conventional MIR spectrometers is severely limited by excessive noises for existing infrared sensors, which hinders widespread use in photon‐scarce scenarios. Here, a broadband MIR single‐photon time‐stretch spectrometer is devised and implemented based on high‐fidelity spectral upconversion and time‐correlated coincidence counting. Specifically, a nanophotonic supercontinuum illumination covering 2.4–4.2 µm is nonlinearly converted to the near‐infrared band, where low‐loss single‐mode fiber and high‐performance silicon detector can be leveraged to facilitate dispersive operation and sensitive detection, respectively. The arrival time for the dispersed upconversion photons is precisely registered with a low‐timing‐jitter photon counter, which enables us to obtain a high spectral resolution about 0.5 cm−1 under a low‐light‐level illumination down to 0.14 photons/nm/pulse. In comparison to previous MIR upconversion spectrometers, the presented time‐stretch architecture favors single‐pixel simplicity and high‐throughput acquisition for the single‐photon spectral measurement. The achieved MIR spectroscopic features of broadband spectral coverage, sub‐wavenumber resolution, single‐photon sensitivity, and room‐temperature operation would stimulate immediate applications in material and life sciences. [ABSTRACT FROM AUTHOR]

BACKGROUND: Obesity induces insulin resistance and chronic inflammation, impacting human health. The relationship between obesity, gut microbiota, and regulatory mechanisms has been studied extensively. Dendrobium officinale polysaccharide (DOP), a traditional Chinese herbal medicine, potentially reduces insulin resistance. However, the mechanism through which DOP affects gut microbiota and alleviates obesity‐induced insulin resistance in rats requires further investigation. RESULTS: The current study aimed to assess the impact of DOP on gut microbiota and insulin resistance in rats on a high‐fat diet. The results revealed that DOP effectively reduced blood lipids, glucose disorders, oxidative stress, and inflammatory infiltration in the liver of obese Sprague Dawley rats. This was achieved by downregulating SOCS3 expression and upregulating insulin receptor substrate‐1 (IRS‐1) by regulating the JAK/STAT/SOCS3 signaling pathway. Notably, DOP intervention enhanced the abundance of beneficial gut microbiota and reduced harmful microbiota. Correlation analysis demonstrated significant associations among intestinal microbiota, SOCS3‐mediated IRS‐1 expression, and inflammatory factors. CONCLUSION: Dendrobium officinale polysaccharide regulated the gut microbiota, enhanced IRS‐1 expression, and mitigated liver injury and insulin resistance due to a high‐fat diet. These findings depict the potential anti‐insulin resistance properties of DOP and offer further evidence for addressing obesity and its complications. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Sensitive and fast mid‐infrared (MIR) spectroscopy is highly attractive in a variety of applications including astronomical observation, pharmaceutical synthesis, and environmental monitoring. However, the performance of conventional MIR spectrometers has long been hindered by the limited sensitivity of narrow‐bandgap detectors and/or the deficient brightness of broadband light sources. Here, an ultra‐sensitive and broadband MIR upconversion spectrometer, which integrates a supercontinuum source covering 1.5–4.2 μ$\umu$m based on a silicon nitride nanophotonic waveguide, is devised and integrated. High‐efficiency and low‐noise nonlinear frequency upconversion is realized based on coincidence pulsed pumping with spectro‐temporal optimization, which enables leverage of silicon detectors for facilitating MIR single‐photon spectroscopy at 0.2 photons/nm/pulse. Furthermore, the upconversion‐based array spectrometer is manifested with high‐speed spectral acquisition rates beyond 200 kHz, which is about tenfold faster than the state‐of‐the‐art scan rates for FTIR‐based spectrometers at a comparable spectral resolution. The achieved features of broadband spectral coverage, single‐photon sensitivity, and sub‐MHz refreshing rate might open up new possibilities for infrared transient spectral measurements in combustion analysis, high‐throughput sorting, and reaction tracking, among others. [ABSTRACT FROM AUTHOR]

Edge enhanced imaging via the spiral phase contrast enables to reveal the phase or amplitude gradients of a target, which has been proved useful in feature recognition, machine vision, and object identification. A long quest is to extend the operation wavelength into the mid‐infrared (MIR) region, as highly demanded in various fields including infrared sensing, astronomic observation, and biomedical diagnosis. Here, ultra‐sensitive MIR imaging at the single‐photon level based on nonlinear frequency upconversion is demonstrated, where the spectrally converted replica of the MIR object image at 3070 nm is captured by a silicon electron multiplying charged coupled device. The imaging sensitivity is significantly improved by the coincidence pulsed pumping with a spectro‐temporal optimization. Furthermore, the edge enhancement is realized by imprinting the spiral phase pattern of the pump onto the upconverted field at the Fourier plane within the nonlinear crystal. Such a nonlinear spatial filter not only provides an effective way to implement the required high‐fidelity vortex screening in the edge enhanced detection, but also renders the MIR illumination into a visible image in an efficient and low‐noise fashion. The presented system for MIR edge enhanced imaging might facilitate immediate applications in label‐free histopathological diagnosis and non‐destructive defect inspection. [ABSTRACT FROM AUTHOR]

In this invited paper, we present an overview of the multi‐pixel photon counter (MPPC), which is a kind of spatial‐multiplexed photon‐number‐resolving detector. We review the operation principles of MPPC, its characterization via quantum detector tomography, and the applications of this detector in research fields such as quantum information, remote sensing and biological medicine. Finally, we discuss the current progress on the improvement of MPPC. [ABSTRACT FROM AUTHOR]

We examine the evidence for large‐scale tropical hydroclimate changes over the Common Era based on a compilation of 67 tropical hydroclimate records from 55 sites and assess the consistency between the reconstructed hydroclimate changes and those simulated by transient model simulations of the last millennium. Our synthesis of the proxy records reveals several regionally coherent patterns on centennial time scales. From 800 to 1000 CE, records from the eastern Pacific and parts of Mesoamerica indicate a pronounced drying event relative to background conditions of the Common Era. In addition, 1400–1700 CE is marked by pronounced hydroclimate changes across the tropics, including dry and/or isotopically enriched conditions in South and East Asia, wet and/or isotopically depleted conditions in the central Andes and southern Amazon in South America, and fresher and/or isotopically depleted conditions in the Maritime Continent. We find notable dissimilarities between the regional hydroclimate changes and global‐scale and hemispheric‐scale temperature reconstructions, indicating that more work needs to be done to understand the mechanisms of the widespread tropical hydroclimate changes during the LIA. Apropos to previous interpretations of large‐scale reorganization of tropical Pacific climate during the LIA, we do not find support for a large‐scale southward shift of the Pacific Intertropical Convergence Zone, while evidence for a strengthened Pacific Walker Circulation and/or an equatorward contraction of the monsoonal Asian‐Australian rain belt exists from limited geographic regions but require additional paleoclimate constraints. Transient climate model simulations exhibit weak forced long‐term tropical rainfall changes over the last millennium but provide several important insights to the proxy reconstructions. Key Points: A synthesis of 67 tropical hydroclimate records from 55 sites indicate several regionally coherent patterns of change in the Common EraRobust patterns include a regional drying event from 800 to 1000 CE and a range of tropical hydroclimate changes ∼1400–1700 CETransient model simulations provide several new insights to the proxy reconstructions [ABSTRACT FROM AUTHOR]

Genetic variation plays a fundamental role in pathogen's adaptation to environmental stresses. Pathogens with low genetic variation tend to survive and proliferate more poorly due to their lack of genotypic/phenotypic polymorphisms in responding to fluctuating environments. Evolutionary theory hypothesizes that the adaptive disadvantage of genes with low genomic variation can be compensated for structural diversity of proteins through post‐translation modification (PTM) but this theory is rarely tested experimentally and its implication to sustainable disease management is hardly discussed. In this study, we analyzed nucleotide characteristics of eukaryotic translation elongation factor‐1α (eEF‐lα) gene from 165 Phytophthora infestans isolates and the physical and chemical properties of its derived proteins. We found a low sequence variation of eEF‐lα protein, possibly attributable to purifying selection and a lack of intra‐genic recombination rather than reduced mutation. In the only two isoforms detected by the study, the major one accounted for >95% of the pathogen collection and displayed a significantly higher fitness than the minor one. High lysine representation enhances the opportunity of the eEF‐1α protein to be methylated and the absence of disulfide bonds is consistent with the structural prediction showing that many disordered regions are existed in the protein. Methylation, structural disordering, and possibly other PTMs ensure the ability of the protein to modify its functions during biological, cellular and biochemical processes, and compensate for its adaptive disadvantage caused by sequence conservation. Our results indicate that PTMs may function synergistically with nucleotide codes to regulate the adaptive landscape of eEF‐1α, possibly as well as other housekeeping genes, in P. infestans. Compensatory evolution between pre‐ and post‐translational phase in eEF‐1α could enable pathogens quickly adapting to disease management strategies while efficiently maintaining critical roles of the protein playing in biological, cellular, and biochemical activities. Implications of these results to sustainable plant disease management are discussed. [ABSTRACT FROM AUTHOR]

Climate change and pesticide resistance are two of the most imminent challenges human society is facing today. Knowledge of how the evolution of pesticide resistance may be affected by climate change such as increasing air temperature on the planet is important for agricultural production and ecological sustainability in the future but is lack in scientific literatures reported from empirical research. Here, we used the azoxystrobin‐Phytophthora infestans interaction in agricultural systems to investigate the contributions of environmental temperature to the evolution of pesticide resistance and infer the impacts of global warming on pesticide efficacy and future agricultural production and ecological sustainability. We achieved this by comparing azoxystrobin sensitivity of 180 P. infestans isolates sampled from nine geographic locations in China under five temperature schemes ranging from 13 to 25°C. We found that local air temperature contributed greatly to the difference of azoxystrobin tolerance among geographic populations of the pathogen. Both among‐population and within‐population variations in azoxystrobin tolerance increased as experimental temperatures increased. We also found that isolates with higher azoxystrobin tolerance adapted to a broader thermal niche. These results suggest that global warming may enhance the risk of developing pesticide resistance in plant pathogens and highlight the increased challenges of administering pesticides for effective management of plant diseases to support agricultural production and ecological sustainability under future thermal conditions. [ABSTRACT FROM AUTHOR]

A fuzzy clustering method with linguistic information is introduced. It uses a minimizing cross‐entropy model to avoid setting the clustering threshold artificially. During the clustering, the semantics of the linguistic information is conservatively represented by solving a programming. It maximizes the potential differences between the objects to be clustered, and further helps an analyst to reach a semantics‐robust clustering result. A case study on clustering a sample destination set, which includes 13 Asia Pacific regions, based on a group of tourists' perceptions is also proposed. [ABSTRACT FROM AUTHOR]

Temperature plays a multidimensional role in host–pathogen interactions. As an important element of climate change, elevated world temperature resulting from global warming presents new challenges to sustainable disease management. Knowledge of pathogen adaptation to global warming is needed to predict future disease epidemiology and formulate mitigating strategies. In this study, 21 Phytophthora infestans isolates originating from seven thermal environments were acclimated for 200 days under stepwise increase or decrease of experimental temperatures and evolutionary responses of the isolates to the thermal changes were evaluated. We found temperature acclimation significantly increased the fitness and genetic adaptation of P. infestans isolates at both low and high temperatures. Low‐temperature acclimation enforced the countergradient adaptation of the pathogen to its past selection and enhanced the positive association between the pathogen's intrinsic growth rate and aggressiveness. At high temperatures, we found that pathogen growth collapsed near the maximum temperature for growth, suggesting a thermal niche boundary may exist in the evolutionary adaptation of P. infestans. These results indicate that pathogens can quickly adapt to temperature shifts in global warming. If this is associated with environmental conditions favoring pathogen spread, it will threaten future food security and human health and require the establishment of mitigating actions. [ABSTRACT FROM AUTHOR]

Gene flow is an important evolutionary force that enables adaptive responses of plant pathogens in response to changes in the environment and plant disease management strategies. In this study, we made a direct inference concerning gene flow in the Irish famine pathogen Phytophthora infestans between two of its hosts (potato and tomato) as well as between China and India. This was done by comparing sequence characteristics of the eukaryotic translation elongation factor 1 alpha (eEF‐1α) gene, generated from 245 P. infestans isolates sampled from two countries and hosts. Consistent with previous results, we found that eEF‐1α gene was highly conserved and point mutation was the only mechanism generating any sequence variation. Higher genetic variation was found in the eEF‐1α sequences in the P. infestans populations sampled from tomato compared to those sampled from potato. We also found the P. infestans population from India displayed a higher genetic variation in the eEF‐1α sequences compared to China. No gene flow was detected between the pathogen populations from the two countries, which is possibly attributed to the geographic barrier caused by Himalaya Plateau and the minimum cross‐border trade of potato and tomato products. The implications of these results for a sustainable management of late blight diseases are discussed. [ABSTRACT FROM AUTHOR]

We demonstrate that self‐propagating sintering reaction could be activated and dramatically enhanced by laser excitation of ion dopants in the solid‐state reactants. Near‐resonant laser absorption and subsequent nonradiative decays make the solid‐state reactants be sintered efficiently while ionic excitations catalyze self‐propagating solid‐state reactions. As a prototype demo, we synthesized white light upconversion phosphors NaYbF4:Pr3+/Gd3+. A continuous‐wave laser at 980 nm was used to populate Yb3+ ions in YbF3 to excited level, which react with NaF to preform NaYbF4 nuclei. The preformed nuclei enhanced laser excitation and energy transfer to those ions that could not be directly excited by the pump laser and thus enabled self‐propagating solid‐state sintering synthesis of NaYbF4 microcrystals at quite low laser powers. Laser excitation of Yb3+ ions could also benefit facile rare‐earth ion doping through activated self‐propagating reactions. Gd3+ and Pr3+ ions were doped in NaYbF4 by simply adding Gd3+ and Pr3+ ionic oxides or fluorides in the raw materials. In addition, Gd3+ ions doping in F− anions ambient could transform the NaYbF4 microcrystal phase from cubic to hexagonal and tune upconversion photoluminescence. This synthetic method can be widely applied to synthesize many other solid‐state compounds, perovskite solar cells, photocatalysts, solid oxide fuel cells, and so forth. [ABSTRACT FROM AUTHOR]

Expected global changes in environmental conditions underline the need for a better understanding of genetic variation in ecological traits and their strategies of adaptation to the stresses. In this study, evolutionary mechanisms and processes of UV adaptation in plant pathogens were investigated by combining statistical genetics, physiological assays, and common garden experiment approaches in an assessment of the potato late blight pathogen, Phytophthora infestans, sampled from various geographic locations in China. We found spatial divergence caused by diversifying selection in UV tolerance among P. infestans populations. Local UV radiation was the driving force of selection as indicated by a positive correlation between UV tolerance in P. infestans populations and the altitude of collection sites. Plasticity accounted for 68% of population variation while heritability was negligible, suggesting temporary changes in gene expression and/or enzymatic activity play a more important role than permanent modification of gene structure in the evolution of UV adaptation. This adaptation strategy may explain the lack of fitness penalty observed in genotypes with higher UV tolerance. [ABSTRACT FROM AUTHOR]

Abstract: Effectors, a group of small proteins secreted by pathogens, play a critical role in the antagonistic interaction between plant hosts and pathogens through their dual functions in regulating host immune systems and pathogen infection capability. In this study, evolution in effector genes was investigated through population genetic analysis of Avr3a sequences generated from 96 Phytophthora infestans isolates collected from six locations representing a range of thermal variation and cropping systems in China. We found high genetic variation in the Avr3a gene resulting from diverse mechanisms extending beyond point mutations, frameshift, and defeated start and stop codons to intragenic recombination. A total of 51 nucleotide haplotypes encoding 38 amino acid isoforms were detected in the 96 full sequences with nucleotide diversity in the pathogen populations ranging from 0.007 to 0.023 (mean = 0.017). Although haplotype and nucleotide diversity were high, the effector gene was dominated by only three haplotypes. Evidence for a selective sweep was provided by (i) the population genetic differentiation (GST) of haplotypes being lower than the population differentiation (FST) of SSR marker loci; and (ii) negative values of Tajima's D and Fu's FS. Annual mean temperature in the collection sites was negatively correlated with the frequency of the virulent form (Avr3aEM), indicating Avr3a may be regulated by temperature. These results suggest that elevated air temperature due to global warming may hamper the development of pathogenicity traits in P. infestans and further study under confined thermal regimes may be required to confirm the hypothesis. [ABSTRACT FROM AUTHOR]

Summary: Background: Cases of pancreatitis were identified in the eluxadoline clinical development program, reflected in initial product labelling, and the subject of postmarketing reports. Aim: To analyse postmarketing cases of eluxadoline‐associated pancreatitis. Methods: We retrospectively analysed all US adverse event reports of pancreatitis associated with eluxadoline reported to the FDA Adverse Event Reporting System (FAERS) database from May 27, 2015 through February 15, 2017. Results: The analysis included 119 cases of pancreatitis associated with eluxadoline; one resulted in death and 75 in hospitalisation. Sixty‐seven cases reported the presence (n = 12) or absence (n = 55) of the patient's gallbladder. The eluxadoline dose received in the 55 cases of patients without gallbladders was 75 mg (n = 43), 100 mg (n = 5), or not reported (n = 7). Of the 119 cases, 37 reported the patient did not abuse alcohol and 82 did not report the alcohol abuse status. The single fatal case occurred in a patient without a gallbladder who received eluxadoline 75 mg and did not abuse alcohol. Forty‐seven cases reported development of pancreatitis within the first or second dose of eluxadoline initiation. The median time to onset for the development of pancreatitis (n = 83) was 1 day, ranging from 1 to 56 days of continued use of eluxadoline. Conclusion: The FAERS cases suggest that patients with or without a gallbladder receiving eluxadoline are at risk for the development of pancreatitis. However, patients without a gallbladder, despite receiving the recommended lower dose of eluxadoline 75 mg and screening for alcohol abuse, appear to be overrepresented among patients who developed eluxadoline‐associated pancreatitis. [ABSTRACT FROM AUTHOR]

Abstract: The spread of antimicrobial resistance and global change in air temperature represent two major phenomena that are exerting a disastrous impact on natural and social issues but investigation of the interaction between these phenomena in an evolutionary context is limited. In this study, a statistical genetic approach was used to investigate the evolution of antimicrobial resistance in agricultural ecosystem and its association with local air temperature, precipitation, and UV radiation. We found no resistance to mancozeb, a nonspecific fungicide widely used in agriculture for more than half a century, in 215 Alternaria alternata isolates sampled from geographic locations along a climatic gradient and cropping system representing diverse ecotypes in China, consistent with low resistance risk in many nonspecific fungicides. Genetic variance accounts for ~35% of phenotypic variation, while genotype–environment interaction is negligible, suggesting that heritability plays a more important role in the evolution of resistance to mancozeb in plant pathogens than phenotypic plasticity. We also found that tolerance to mancozeb in agricultural ecosystem is under constraining selection and significantly associated with local air temperature, possibly resulting from a pleiotropic effect of resistance with thermal and other ecological adaptations. The implication of these results for fungicide and other antimicrobial management in the context of global warming is discussed. [ABSTRACT FROM AUTHOR]

Background Chronic hepatitis C virus ( HCV) infection is the leading cause of cirrhosis and hepatocellular carcinoma ( HCC) in the United States ( US) and an emerging cause in China. Aim To compare the clinical characteristics of hepatitis C patients in the US and China, and factors influencing disease stage. Methods Prospective study of 2 cohorts of HCV patients recruited at 1 site in the US and 3 sites in China. Standardised questionnaire on risk factors and medical history were used and diagnosis of cirrhosis and HCC was based on pre-defined criteria. Results One thousand nine hundred and fifty seven patients (1000 US and 957 China) were enrolled. US patients were more likely to be men (61.4% vs 48.5%), older (median age 57 vs 53 years), obese (38.4% vs 16.8%) and diabetic (21.8% vs 10.8%). A significantly higher per cent of US patients had cirrhosis (38.2% vs 16.0%) and HCC (14.1% vs 2.7%). Investigator estimated time at infection in US was 10 years earlier than in Chinese patients but US patients were more likely to have advanced disease even after stratifying for duration of infection. Study site in the US, older age, truncal obesity, diabetes and prior HCV treatment were significant predictors of advanced disease on multivariate analysis. Conclusions HCV patients in the US had more advanced liver disease than those in China. We speculate that underlying fatty liver disease may be a major contributor to this difference, and management of glycometabolic abnormalities should occur in parallel with anti-viral therapy to achieve optimal outcomes. [ABSTRACT FROM AUTHOR]

Hereditary non-polyposis colorectal cancer (HNPCC), the most common type of hereditary colorectal cancer, is thought to be a simple Mendelian disease involving DNA mismatch repair genes. The majority of mutations associated with HNPCC occur in the hMSH2 and hMLH1 genes. The reported incidence of mismatch repair gene mutations in HNPCC kindreds varies considerably (from 22 to 86%), and most mutations are unique. This study aimed to determine the genetic basis of Taiwanese HNPCC kindreds, focusing on the two major genes involved in this disease. A total of 15 Taiwanese HNPCC kindreds meeting the Amsterdam criteria, including 72 affected individuals among a total of 266 individuals, were analyzed using both RNA- and DNA-based methods. The mutation rate of hMSH2 and hMLH1 in these 15 kindreds was 0% and 20%, respectively, which is lower than that reported in other countries. Two novel mutations were discovered in hMLH1: one was an allelic loss of a 5.2-kb genomic fragment causing exon 16 deletion; and the other was a two-nucleotide deletion that resulted in a frameshift mutation of exon 3. We also identified one hMLH1 exon 4 mutation (a C to T transition in codon 117), which had been reported previously in western countries. This is the first genetic study of HNPCC from Taiwan. [ABSTRACT FROM AUTHOR]

Temperature is one of the most important environmental parameters with crucial impacts on nearly all biological processes. Due to anthropogenic activity, average air temperatures are expected to increase by a few degrees in coming decades, accompanied by an increased occurrence of extreme temperature events. Such global trends are likely to have various major impacts on human society through their influence on natural ecosystems, food production and biotic interactions, including diseases. In this study, we used a combination of statistical genetics, experimental evolution and common garden experiments to investigate the evolutionary potential for thermal adaptation in the potato late blight pathogen, Phytophthora infestans, and infer its likely response to changing temperatures. We found a trade-off associated with thermal adaptation to heterogeneous environments in P. infestans, with the degree of the trade-off peaking approximately at the pathogen's optimum growth temperature. A genetic trade-off in thermal adaptation was also evidenced by the negative association between a strain's growth rate and its thermal range for growth, and warm climates selecting for a low pathogen growth rate. We also found a mirror effect of phenotypic plasticity and genetic adaptation on growth rate. At below the optimum, phenotypic plasticity enhances pathogen's growth rate but nature selects for slower growing genotypes when temperature increases. At above the optimum, phenotypic plasticity reduces pathogen's growth rate but natural selection favours for faster growing genotypes when temperature increases further. We conclude from these findings that the growth rate of P. infestans will only be marginally affected by global warming. [ABSTRACT FROM AUTHOR]

In addition to standard postmarketing drug safety monitoring, Section 915 of the Food and Drug Administration Amendments Act of 2007 (FDAAA) requires the US Food and Drug Administration (FDA) to conduct a summary analysis of adverse event reports to identify risks of a drug or biologic product 18 months after product approval, or after 10,000 patients have used the product, whichever is later. We assessed the extent to which these analyses identified new safety signals and resultant safety-related label changes. Among 458 newly approved products, 300 were the subjects of a scheduled analysis; a new safety signal that resulted in a safety-related label change was found for 11 of these products. Less than 2% of 713 safety-related label changes were based on the scheduled analyses. Our study suggests that the safety summary analyses provide only marginal value over other pharmacovigilance activities. [ABSTRACT FROM AUTHOR]

A genomic library was used to develop seven SSR markers for studying the population genetics of Alternaria solani, a pathogenic fungus causing early blight disease of potato and tomato worldwide. Population genetic analysis of 268 isolates of A. solani sampled from four locations, each representing one of four potato production systems in China, indicates that these SSR markers are moderately diverse, selectively neutral and possibly unlinked. Population genetic analysis also indicated that genetic variation of A. solani in China is high. About 2/3 of 123 genotypes were detected only once and genotype diversity measured by the standardized Shannon index ranged between 0·82 and 0·92 in the populations. Although clones were detected in multiple populations separated by thousands of kilometres, random association among SSR loci was found in half of the populations assayed. On average, nearly six copies of genetic material were exchanged among these populations each generation and no isolation by distance was detected. It is hypothesized that the joint effects of cryptic sexual reproduction and human-mediated gene flow may account for the observed population genetic structure of A. solani in China. [ABSTRACT FROM AUTHOR]

Previous empirical studies have, in general, found that a random walk provides an appropriate description of the exchange rate dynamics. What remains at issue is how the error term of the random walk should be parameterised. This study takes an entirely different approach to examining the exchange rate dynamics. Specifically, we employ the bootstrapping technique, coupled with two popular investment strategies, to investigate which of the following nine random walks best portrays the dynamics of the Japanese yen: a random walk whose error term is independent and identically distributed, four random walks whose error terms are ARCH-parameterised, and four random walks whose error terms are GARCH-parameterised. Using daily yen data from 1991 to 2010, our results show that, of the nine processes, the GARCH(1,1) random walk best portrays the yen over the said period. [ABSTRACT FROM AUTHOR]

Background Chronic constipation ( CC) is a highly prevalent health problem, potentially associated with increased risk of colorectal cancer (CRCancer). Aim To investigate the association between CC, its severity, and CRCancer by estimating the relative risk of developing CRCancer and benign colorectal neoplasm ( BCN) among severity-stratified patients with and without CC. Methods Chronic constipation patients from a large retrospective US claims database were matched 1:3 with CC-free controls by demographic characteristics. CRCancer and BCN prevalence were measured over 1 year. In pre-index CRCancer- and BCN-free patients, incidence rate ratios ( IRRs) of new CRCancer and BCN were calculated. Multivariate regression models adjusted for comorbidities and family history. CC patients' disease severity was rated based on CC-related resource use. IRRs for new CRCancer and BCN were estimated for CC severity groups and controls. Results Chronic constipation ( N = 28 854) and CC-free ( N = 86 562) patients had mean age 61.9 years; 66.7% were female. One-year CRCancer prevalence was 2.7% and 1.7%, and BCN prevalence was 24.8% and 11.9% for CC and CC-free patients, respectively. Adjusted IRRs between CC and CC-free patients were 1.59 [95% confidence interval (CI): 1.43-1.78] and 2.60 [95% CI: 1.51-2.70] for CRCancer and BCN, respectively. Patients with severe and very severe CC had significantly greater incidence of CRCancer and BCN. At ≥2 and ≥5 years of observation, CRCancer and BCN incidence remained consistently and significantly higher for CC patients. Conclusions Patients with chronic constipation are associated with significantly higher prevalence and incidence of colorectal cancer and benign colorectal neoplasm than matched chronic constipation-free patients. These risks increase with the severity of chronic constipation. [ABSTRACT FROM AUTHOR]

The multicriteria decision-making problem with an unbalanced linguistic scale is analyzed by multicriteria semantic dominance (MCSD) technique. The technique only requires the available partial semantics information about the scale. The MCSD rules on two types of unbalanced linguistic scale are introduced and proven. With these rules, alternatives are divided into two mutually exclusive sets called the efficient set and inefficient set. The decision maker with a specific type of linguistic scale will never choose the alternative from the corresponding inefficient set as the feasible one. Thus he/she can easily choose from the original alternative set. An example is also provided to illustrate the procedure of the proposed method. [ABSTRACT FROM AUTHOR]

The article discusses the use of loop-mediated isothermal amplification (LAMP) to detect abalone shrivelling syndrome-associated virus. It provides an overview about the marine gastropod mollusc Haliotis diversicolor Reeve and LAMP. It also suggests that the LAMP method was successfully modified in the study for AbSV detection, demonstrating high specificity and sensitivity at a level similar to other reported PCR methods for viral detection in molluscs.

Agrobacterium tumefaciens is a Gram-negative bacterium. It causes plants to produce crown gall disease because of the transfer, integration and expression of oncogenes encoded by the T- DNA (transferred DNA) region of the tumour-inducing ( Ti) plasmid. A set of transferred genes directs the production of bacterial nutrients, called opines, formed by condensation of an amino acid and a keto acid or a sugar. Transformed cells synthesize and secrete substantial quantities of particular opines, which A. tumefaciens then uses as a carbon and sometimes nitrogen source. Agrobacterium tumefaciens strains are usually classified on the basis of the opines they can catabolize. Because of the ability to transfer DNA between different kingdoms, A. tumefaciens is also frequently used to generate transgenic plants. This study analyses five poorly characterized wildtype Agrobacterium strains, 1D1108, 1 D1460, 1 D132, 1 D1478 and 1 D1487, isolated from Euonymus, cane, cherry, Salix and apple, respectively. Partial Ti-plasmid sequence analysis demonstrated that the five strains harbour the nopaline-type Ti plasmid. Tumorigenesis and transient transformation assays of the five analysed and six wildtype A. tumefaciens strains were performed with selected plant species, including two or three species of Brassicaceae, Asteraceae, Solanaceae, Apiaceae and Leguminosae. The A. tumefaciens strains 1 D1108, 1 D1460 and 1 D1478 showed higher transformation efficiencies than the previously characterized A. tumefaciens strains with several economically important crops. These data suggest the potential use of these newly characterized wildtype A. tumefaciens strains in transient transformation assays with certain plant species. [ABSTRACT FROM AUTHOR]

Aims To assess associations between hypoglycaemia and risk of accidents resulting in hospital visits among people with type 2 diabetes receiving antidiabetes drugs without insulin. Methods People with type 2 diabetes who were not treated with insulin were identified from a US-based employer claims database (1998-2010). Following initiation of an antidiabetes drug, the occurrence of accidents resulting in hospital visits was compared between people with, and without, claims for hypoglycaemia using multivariable Cox proportional hazard models adjusted for demographics, comorbidities, prior treatments and prior medical service use. Additional analyses were stratified by age 65 years or older. Results A total of N = 5582 people with claims for hypoglycaemia and N = 27 910 with no such claims were included. Accidents resulting in hospital visits occurred in 5.5 and 2.8% of people with, and without, hypoglycaemia, respectively. After adjusting for baseline characteristics, hypoglycaemia was associated with significantly increased hazards for any accident [hazard ratio ( HR) 1.39, 95% CI 1.21-1.59, p < 0.001], accidental falls ( HR 1.36, 95% CI 1.13-1.65, p < 0.001) and motor vehicle accidents ( HR 1.82, 95% CI 1.18-2.80, p = 0.007). In age-stratified analyses, hypoglycaemia was associated with greater hazards of driving-related accidents in people younger than age 65 and falls in people aged 65 or older. Conclusions In people with type 2 diabetes receiving antidiabetes drugs without insulin, hypoglycaemia was associated with a significantly higher risk of accidents resulting in hospital visits, including accidents related to driving and falls. [ABSTRACT FROM AUTHOR]

Aim To determine the long-term outcomes of patients in whom no initial cause for their anaemia is established. Method Six hundred and thirty-nine patients presenting to an iron deficiency anaemia pathway were prospectively entered onto a database. Initial assessment included haematological review, coeliac screen, oesophagogastroduodenoscopy and colonic imaging as per British Society of Gastroenterology guidelines. A 5-year audit of outcomes was undertaken using patient medical records and hospital laboratory databases. Results A diagnosis was found initially in 266 (42%) patients, with 124 (19%) having a gastrointestinal (GI) luminal neoplasm, 54 (8%) of which were malignant. Twelve patients had a nonluminal or non-GI malignancy. Eighty-eight (14%) had benign upper GI bleeding and 23 (4%) had coeliac disease. One hundred and forty-three (22%) did not have confirmed iron deficiency anaemia on review of haematinics. Complete records were available for 595 (93%) patients at 5 years. Of the 373 patients in whom a cause was not initially diagnosed, 6 (2%) were ultimately diagnosed with a GI luminal malignancy and 18 (5%) with a nonluminal or non-GI malignancy. There was no difference in the incidence of malignancies between those with or without confirmed iron deficiency. Conclusions Most patients in whom no cause was found at initial investigation resolve on oral iron supplements. Patients with normal ferritin values had as high an incidence of GI malignancies as those with low values and should be investigated. In the over 50s if the anaemia remains after a course of iron further investigation is recommended as there is a significant incidence of both GI and non-GI pathology. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to describe an easy and reproducible method of measuring clinical performance in colonoscopy. Method: Data from all endoscopy procedures performed within the main endoscopy unit at Derriford Hospital between January and December 2007 were analysed. Points were allocated for given procedures. A local health economic analysis revealed that at least 8 points (or four colonoscopies) must be performed to meet list costs. The clinical performance was described as a capability index of crude Caecal Intubation Rate (CIR) vs the mean Points Performed ⁄ Endoscopy List (points ⁄ list). Results: Overall, 3884 colonoscopies were performed, with a mean crude CIR of 89.6% and 8.3 points ⁄ List. Only 7 ⁄ 23 endoscopists consistently met the Joint Advisory Group on Gastrointestinal Endoscopy (JAG) standard in a cost-effective way. An annual colonoscopy rate of ‡ 150 cases was associated with higher points per list (points ⁄ list) (P = 0.003). Endoscopists offering ‡ 15% of cases as training cases had significantly higher crude CIRs and points ⁄ list (P = 0.051; P = 0.017). Conclusions Clinical performance is a function of quality provided in a cost-effective way. Our capability index is an effective and reproducible way of measuring clinical performance. Training was not associated with reduced volume. [ABSTRACT FROM AUTHOR]

Psoriasis is frequently associated with comorbidities. To estimate the incremental economic burden associated with comorbidities in patients with psoriasis, accounting for psoriasis severity. Patients continuously enrolled ≥ 6 months after a randomly selected psoriasis diagnosis date were selected from the Ingenix Impact National Managed Care Database (1999-2004). Comorbidities identified during the 6-month study included: psoriatic arthritis, cardiovascular disease, depression, diabetes, hyperlipidemia, hypertension, obesity, cerebrovascular diseases and peripheral vascular disease. Resource utilization and costs during the 6-month follow-up period were compared for patients with ≥ 1 comorbidity vs. those without and for patients with a specific comorbidity vs. those without. Adjusted incidence rate ratios (IRRs) and odds ratios (ORs) were estimated for resource utilization using negative binomial and logistic regression models, respectively. Adjusted incremental costs associated with comorbidities were reported using general linear models with log-link and gamma distributions or two-part models. Models controlled for age, sex and psoriasis severity. A total of 114 512 patients were included; 51% had ≥ 1 comorbidity. Hyperlipidemia (27%) and hypertension (25%) were most prevalent. Patients with comorbidities were more likely to experience urgent care [OR (95% confidence interval (CI)) = 1.58 (1.51-1.65)] than patients without comorbidities. They also had significantly greater hospitalization rates [IRR (95% CI) = 2.27 (2.13-2.42)] and outpatient visits [IRR (95% CI) = 1.53 (1.52-1.55)]. Compared with patients who did not have comorbidities, patients with comorbidities incurred $2184 ( P < 0.001) greater total costs. Comorbidities present a significant economic burden in patients with psoriasis. [ABSTRACT FROM AUTHOR]

Aliment Pharmacol Ther 2010; 32: 1228–1239 Summary: Background  Adalimumab induces and maintains remission in adults with Crohn's disease. Aim  To evaluate safety, fistula healing, quality of life and work productivity in adalimumab‐treated patients who failed infliximab, including primary nonresponders. Methods  After a ≥8‐week infliximab washout, patients with moderate‐to‐severe Crohn's disease received open‐label adalimumab as induction (160/80 mg at weeks 0/2) and maintenance (40 mg every other week) therapies. At/after 8 weeks, patients with flare/nonresponse could receive weekly therapy. Minimum study duration was 8 weeks, continuing until the commercial availability of adalimumab for Crohn's disease. Results  Of 673 patients enrolled, 17% were infliximab primary nonresponders and 83% were initial responders. Three percent of patients had serious infections (mainly abscesses). Complete fistula healing was achieved by 34/88 (39%) patients with baseline fistulas. Improvements in quality of life and work productivity were sustained from week 4 to week 24 for all patients, as well as the subgroup of primary nonresponders. Conclusions  Blinded clinical trials have shown adalimumab to be both an effective first‐line therapy for anti‐TNF‐naïve patients and an important treatment option for infliximab‐refractory or ‐intolerant patients. This trial presents open‐label experience to support further the safety and effectiveness of adalimumab in patients who failed infliximab therapy, including primary nonresponders (NCT00338650). [ABSTRACT FROM AUTHOR]

Aliment Pharmacol Ther 31, 693–707 Background Early onset and complications such as hospitalization and surgery contribute to the economic burden of ulcerative colitis. Aim To review systematically the literature on costs of ulcerative colitis in Western countries. Methods Studies estimating costs of ulcerative colitis in Western countries were identified using Medline, EMBASE and ISI Web of Science and were rated based on relevance and reliability of estimates. All costs were adjusted to 2008 currency values. A parallel review focused on the impact of disease severity on costs, hospitalizations and surgeries. Results Estimated annual per-patient direct medical costs of ulcerative colitis ranged from $6217 to $11 477 in the United States and from €8949 to €10 395 in Europe. Hospitalizations accounted for 41–55% of direct medical costs. Indirect costs accounted for approximately one-third of total costs in the United States and 54–68% in Europe. Total economic burden of ulcerative colitis was estimated at $8.1–14.9 billion annually in the United States and at €12.5–29.1 billion in Europe; total direct costs were $3.4–8.6 billion in the United States and €5.4–12.6 billion in Europe. Direct costs, hospitalizations and surgeries increased with worsening disease severity. Conclusions Ulcerative colitis is a costly disease. Hospitalizations contribute significantly to direct medical costs, and indirect costs are considerable, having previously been substantially underestimated. [ABSTRACT FROM AUTHOR]

Background Our team previously demonstrated arterial stiffening and cardiac hypertrophy in type 2 diabetic rats at 8 but not 4 weeks after being administered streptozotocin (STZ) and nicotinamide (NA). The present study focused on investigating the effects of type 2 diabetes on cardiac autonomic nerve function in the STZ- and NA-treated animals, using modern spectral estimation technique. Design An autoregressive process was performed to each detrended signal of heart rate and systolic blood pressure measured in the 4- and 8-week STZ-NA rats with anaesthesia. The power of low-frequency and high-frequency oscillations was automatically quantified with each spectral peak by computing the residuals. The closed-loop baroreflex gain was estimated using the square root of the ratio between heart rate and systolic blood pressure powers in the low-frequency band. Results Compared with the age-matched controls, both the 4- and 8-week STZ-NA diabetic rats had significantly decreased low-frequency oscillations of heart rate but not systolic blood pressure variability, showing a decline in baroreflex gain (0·451 ± 0·060 and 0·484 ± 0·056 vs. 1·196 ± 0·064 ms mmHg−1, P < 0·05). On the other hand, the low frequency–high frequency power ratio of the heart period was also diminished in the two diabetic groups, indicating a shift in sympatho-vagal balance of the heart control (0·472 ± 0·109 and 0·504 ± 0·090 vs. 1·857 ± 0·336, P < 0·05). Conclusions The cardiac autonomic dysfunction in the absence of any significant changes in vascular dynamics, 4 but not 8 weeks after induction of type 2 diabetes, suggests that the diabetic autonomic neuropathy may precede arterial stiffening and cardiac hypertrophy in the STZ- and NA-treated rats. [ABSTRACT FROM AUTHOR]

Background and Purpose: Aminoguanidine (AG), an inhibitor of advanced glycation endproducts, has been shown to prevent arterial stiffening and cardiac hypertrophy in streptozotocin (STZ) and nicotinamide (NA)-induced type 2 diabetes in rats. Our aims were to examine whether AG produced benefits on cardiac pumping mechanics in the STZ and NA-treated animals in terms of maximal systolic elastance (E(max)) and theoretical maximum flow (Q(max)).Experimental Approach: After induction of type 2 diabetes, rats received daily injections of AG (50 mg kg(-1), i.p.) for 8 weeks and were compared with age-matched, untreated, diabetic controls. Left ventricular (LV) pressure and ascending aortic flow signals were recorded to calculate E(max) and Q(max), using the elastance-resistance model. Physically, E(max) reflects the contractility of the myocardium as an intact heart, whereas Q(max) has an inverse relationship with the LV internal resistance.Key Results: Both type 2 diabetes and AG affected E(max) and Q(max), and there was an interaction between diabetes and AG for these two variables. The E(max) and Q(max) were reduced in rats with type 2 diabetes, but showed a significant rise after administration of AG to these diabetic rats. Moreover, the increase in Q(max) corresponded to a decrease in total peripheral resistance of the systemic circulation when the STZ and NA-induced diabetic rats were treated with AG.Conclusions and Implications: AG therapy prevented not only the contractile dysfunction of the heart, but also the augmentation in LV internal resistance in rats with STZ and NA-induced type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background and purpose:Aminoguanidine (AG), an inhibitor of advanced glycation endproducts, has been identified as a prominent agent that prevents the fructose-induced arterial stiffening in male Wistar rats. Our aims were to examine whether AG produced benefits on the left ventricular (LV)-arterial coupling in fructose-fed (FF) animals in terms of the ventricular and arterial chamber properties.Experimental approach:Rats given 10% fructose in drinking water (FF) were daily treated with AG (50 mg·kg−1, i.p.) for 2 weeks and compared with the untreated FF group. In anaesthetised rats, LV pressure and ascending aortic flow signals were recorded to calculate LV end-systolic elastance (E es, an indicator of myocardial contractility) and effective arterial volume elastance (E a). The optimal afterload (Q load) determined by the ratio of E a to E es was used to measure the coupling efficiency between the left ventricle and its vasculature.Key results:There was a significant interaction between fructose and AG in their effects on E a. Fructose loading significantly elevated E a and AG prevented the fructose-derived deterioration in arterial chamber elastance. Both fructose and AG affected E es and Q load, and there was an interaction between fructose and AG for these two variables. Both E es and Q load exhibited a decline with fructose feeding but showed a significant rise after AG treatment in the FF rats.Conclusions and Implications:AG prevented not only the contractile dysfunction of the heart caused by fructose loading, but also the fructose-induced deterioration in matching left ventricular function to the arterial system.British Journal of Pharmacology (2007) 151, 341–346; doi:10.1038/sj.bjp.0707223; published online 2 April 2007 [ABSTRACT FROM AUTHOR]

Tnticum aestivum cv. 'Chinese Spring, which carries the homneologous-pairing suppressor Phi on chromosome SB, was crossed with rye and octoploid Agrotricum, as were the ph1b mutant and nulli5B- tetra5D (N5BT5D). In the hybrids with rye, Ph1 conditioned a low frequency of homoenlogous pairing, N5BT5D a middle frequency and ph1b a high frequency. Among the Agrotricum hybrids, only those involving ph1b showed numerous multivalents. Thus ph1b should be more useful than N5BT5D for inducing the transfer of genes from rye and Agropyron to wheat. B-chromosomes from rye largely suppressed homoeologous pairing. [ABSTRACT FROM AUTHOR]

A 5-month-old boy with hypoplastic left heart syndrome developed chylothorax and oedema of the left upper arm more than 2 months after recovering from a Norwood stage II operation. Venography showed occlusion of the innominate vein with abundant collaterals crossing the midline to join the right internal jugular vein. The occlusion was caused by a peripherally inserted central catheter under systemic heparinisation. This case highlights the importance of a patent venous pathway, especially in patients with a cavopulmonary connection in the upper extremities. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the impact on the abnormality of arterioarterial anastomosis on early-onset umbilical artery flow in a monochorionic-diamniotic twin.