To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
OBJECTIVES/SPECIFIC AIMS: The aim of this study is to determine whether quantitative measures of knee structures including effusion, bone marrow lesions, cartilage, and meniscal damage can improve upon an existing model of demographic and clinical characteristics to classify accelerated knee osteoarthritis (AKOA). METHODS/STUDY POPULATION: We conducted a case-control study using data from baseline and four annual follow-up visits from the osteoarthritis initiative. Participants had no radiographic knee osteoarthritis (KOA) at baseline. AKOA is defined as progressing from no KOA to advance-stage KOA in at least 1 knee within 48 months. AKOA knees were matched 1:1 based on sex to (1) participants who did not develop KOA within 48 months and (2) participants who developed KOA but not AKOA. Analyses were person based. Classification and regression tree analysis was used to determine the important variables and percent of variance explained. RESULTS/ANTICIPATED RESULTS: A previous classification and regression tree analysis found that age, BMI, serum glucose, and femorotibial angle explained 31% of the variability between those who did and did not develop AKOA. Including structural measurements as candidate variables yielded a model that included effusion, BMI, serum glucose, cruciate ligament degeneration and coronal slope and explained 39% of the variability. DISCUSSION/SIGNIFICANCE OF IMPACT: Knee structural measurements improve classification of participants who developed AKOA Versus those who did not. Further research is needed to better classify patients at risk for AKOA.
Family history is a long-standing and readily obtainable risk factor for schizophrenia (SCZ). Low-cost genotyping technologies have enabled large genetic studies of SCZ, and the results suggest the utility of genetic risk scores (GRS, direct assessments of inherited common variant risk). Few studies have evaluated family history and GRS simultaneously to ask whether one can explain away the other.
We studied 5959 SCZ cases and 8717 controls from four Nordic countries. All subjects had family history data from national registers and genome-wide genotypes that were processed through the quality control procedures used by the Psychiatric Genomics Consortium. Using external training data, GRS were estimated for SCZ, bipolar disorder (BIP), major depression, autism, educational attainment, and body mass index. Multivariable modeling was used to estimate effect sizes.
Using harmonized genomic and national register data from Denmark, Estonia, Norway, and Sweden, we confirmed that family history of SCZ and GRS for SCZ and BIP were risk factors for SCZ. In a joint model, the effects of GRS for SCZ and BIP were essentially unchanged, and the effect of family history was attenuated but remained significant. The predictive capacity of a model including GRS and family history neared the minimum for clinical utility.
Combining national register data with measured genetic risk factors represents an important investigative approach for psychotic disorders. Our findings suggest the potential clinical utility of combining GRS and family history for early prediction and diagnostic improvements.
Ocular toxoplasmosis (OT) caused by Toxoplasma gondii is a major cause of infectious uveitis, however little is known about its immunopathological mechanism. Susceptible C57BL/6 (B6) and resistant BALB/c mice were intravitreally infected with 500 tachyzoites of the RH strain of T. gondii. B6 mice showed more severe ocular pathology and higher parasite loads in the eyes. The levels of galectin (Gal)-9 and its receptors (Tim-3 and CD137), interferon (IFN)-γ, IL-6 and IL-10 were significantly higher in the eyes of B6 mice than those of BALB/c mice; however, the levels of IFN-α and -β were significantly decreased in the eyes and CLNs of B6 mice but significantly increased in BALB/c mice after infection. After blockage of galectin–receptor interactions by α-lactose, neither ocular immunopathology nor parasite loads were different from those of infected BALB/c mice without α-lactose treatment. Although the expressions of Gal-9/receptor were significantly increased in B6 mice and Gal-1 and -3 were upregulated in both strains of mice upon ocular T. gondii infection, blockage of galectins did not change the ocular pathogenesis of genetic resistant BALB/c mice. However, IFN-α and -β were differently expressed in B6 and BALB/c mice, suggesting that type I IFNs may play a protective role in experimental OT.
It is imperative to evaluate precise nutrient requirements of animals in order to optimize productivity and minimize feed cost and nutrient excretions. The current non-phytate phosphorus (NPP) recommendation for broilers is based on the papers published 30 years ago. However, today’s commercial birds are quite different from those before 30 years. Therefore, the present experiment was conducted with growing male broiler chickens to evaluate an optimal dietary NPP level of broiler chickens fed a conventional corn–soybean meal diet from 4 to 6 weeks of age. The 1-day-old chicks were fed corn–soybean meal diet containing 0.39% NPP from 1 to 3 weeks of age. At 22 days of age, 360 birds were selected and randomly allotted by BW to one of 10 dietary treatments with six replicate cages of six birds per cage for each treatment. Birds were fed the P-unsupplemented corn–soybean meal basal diet and the basal diet supplemented with inorganic P as CaHPO4·H2O ranging from 0.00% to 0.45% with 0.05% increment from 4 to 6 weeks of age. The dietary NPP levels were 0.09%, 0.14%, 0.20%, 0.24%, 0.30%, 0.34%, 0.38%, 0.45%, 0.49% and 0.54%, respectively, and the dietary Ca level was fixed at 0.90% for all treatments. The results showed that average daily gain, serum inorganic P concentration, tibia bone strength, tibia ash percentage and P percentage, tibia bone mineral content (BMC) and density (BMD), middle toe ash percentage and P percentage, middle toe BMC, total body BMC and BMD were affected (P<0.0001) by dietary NPP level, and increased linearly (P<0.0001) and quadratically (P<0.003) as dietary NPP levels increased. Optimal dietary NPP levels estimated based on fitted broken-line models (P<0.0001) of the above indices are 0.21%, 0.29%, 0.29%, 0.29%, 0.29%, 0.31%, 0.29%, 0.30%, 0.27%, 0.29% and 0.28%, respectively. It is suggested that the total body BMC and BMD, and middle toe ash P and BMC might be new, sensitive and non-invasive criteria to evaluate the dietary NPP requirements of broilers. The optimal dietary NPP level would be 0.31% for broiler chickens fed a conventional corn–soybean meal diet from 4 to 6 weeks of age.
Floral organ development influences plant reproduction and crop yield. The mechanism of floral organ specification is generally conserved in angiosperms as demonstrated by the ‘ABC’ model. However, mechanisms underlying the development of floral organs in specific groups of species such as grasses remain unclear. In the genus Oryza (rice), a spikelet consists of a fertile floret sub-tended by a lemma, a palea, two sterile lemmas and rudimentary glumes. To understand how the lemma is formed, a curve-shaped lemma-distortion1 (ld1) mutant was identified. Genetic analysis confirmed that the ld1 mutant phenotype was due to a single recessive gene mutation. Using a large F2 population, the LD1 gene was mapped between markers Indel-7-15 and Indel-7-18, which encompassed a region of 15·6 kilo base pairs (kbp). According to rice genome annotations, two putative genes, LOC_Os07g32510 and LOC_Os07g32520, were located in this candidate region. However, DNA sequencing results indicated only 1 base pair (bp) substitution (T⇨C) was found in LOC_Os07g32510 between the wild-type and the ld1 mutant. Thus LOC_Os07g32510, encoding a DNA binding with one zinc finger (DoF) containing protein, was the candidate gene for LD1. Further analysis showed that mutation of the amino acid cysteine (C) to arginine (R) was likely to lead to zinc finger protein deactivation. Phylogenetic and conservation analysis of the gene from different species revealed that cysteine was critical to LD1 function. As a new gene controlling lemma development, the study of LD1 could provide insights into rice floral organ formation mechanisms.
Firstly, a brief overview will be given on different models that are able to describe the behaviour of wave propagation as a function of specific frequency ranges. Each range corresponds to different heating systems, namely, 20–100 MHz for the ion cyclotron resonant heating, 2–20 GHz for lower-hybrid heating or current drive, and 100–250 GHz for electron cyclotron resonant heating or current drive systems. The specification of every system will be explained in detail, including the typical set of equations and the assumptions needed to describe the properties of these heating or current drive systems, as well as their specific domains of validity. In these descriptions, special attention will be paid to the boundary conditions. A review of specific physical problems associated with the wave heating systems will also be provided. The review will detail the role of simulation in answering questions that arise from experiments on magnetized plasma devices devoted to fusion. A few examples that will be covered are the impact of edge turbulence on wave propagation and its consequences on heating system performance, the effects of fast particles and ponderomotive effects, among others. A study that is more focused on radio-frequency sheath effects will also be discussed. It shows that such simulations require very sophisticated tools to gain a partial understanding of the observations undertaken in dedicated experiments. To conclude this review, an overview will be given about the requirements and progress necessary to obtain relevant predictive simulation tools able to describe the wave heating systems used in fusion devices.
The Herschel Space Observatory was the fourth cornerstone mission in the European Space Agency (ESA) science programme with excellent broad band imaging capabilities in the sub-mm and far-infrared part of the spectrum. Although the spacecraft finished its observations in 2013, it left a large legacy dataset that is far from having been fully scrutinised and still has a large potential for new scientific discoveries. This is specifically true for the photometric observations of the PACS and SPIRE instruments. Some source catalogues have already been produced by individual observing programs, but there are many observations that risk to remain unexplored. To maximise the science return of the SPIRE and PACS data sets, we are in the process of building the Herschel Point Source Catalogue (HPSC) from all primary and parallel mode observations. Our homogeneous source extraction enables a systematic and unbiased comparison of sensitivity across the different Herschel fields that single programs will generally not be able to provide. The catalogue will be made available online through archives like the Herschel Science Archive (HSA), the Infrared Science Archive (IRSA), and the Strasbourg Astronomical Data Center (CDS).
Arginine kinase (AK) is an important regulation factor of energy metabolism in invertebrate. An arginine kinase gene, named HaAK, was identified to be differentially expressed between Cry1Ac-susceptible (96S) and Cry1Ac-resistant (Bt-R) Helicoverpa armigera larvae using cDNA-amplification fragment length polymorphism analysis. The full-length open reading frame sequence of HaAK gene with 1068 bp was isolated from H. armigera. Quantitative reverse transcription polymerase chain reaction assay revealed that HaAK gene is specifically expressed in multiple tissues and at larval developmental stages. The peak expression level of HaAK was detected in the midgut of the fifth-instar larvae. Moreover, the expression of HaAK was obviously down-regulated in Bt-R larvae. We further constructed a dsRNA vector directly targeting HaAK and employed RNAi technology to control the larvae. The feeding bioassays showed that minute quantities of dsRNA could greatly increase the larval mortality and delay the larval pupation. Silencing of HaAK significantly retarded the larval development, indicating that HaAK is a potential target for RNA interference-based pest management.
We determined the prevalence and seasonality of infections by Fasciola of goats and bovine species (cattle and water buffalo) in Hubei and Anhui provinces of China. Faecal samples were collected at 2- to 3-month intervals from 200 goats in Hubei province and from 152 bovine species in Anhui province. All faecal samples were examined for the presence of parasites. We determined the nucleotide sequences of the first and second internal transcribed spacers (ITS-1 and ITS-2) of the nuclear ribosomal DNA (rDNA) of 39 Fasciola worms from Anhui province. The prevalence of Fasciola infection in goats ranged between 3.5 and 37.0%, with mean eggs per gram (EPG) ranging between 29.0 and 166.0. Prevalence and EPG exhibited downward trends over time with significant differences. The prevalence of Fasciola infection in cattle ranged between 13.3 and 46.2% (mean EPG, 36.4–100.0), and that of water buffalo ranged between 10.3 and 35.4% (mean EPG, 25.0–89.6), with a higher prevalence of infection and EPG from June to October compared with December to March. Analysis of ITS-1 and ITS-2 sequences revealed that F. hepatica and F. gigantica were present in all bovine species of Anhui province and that F. gigantica mainly infected water buffalo. This is the first demonstration of Fasciola infection in Hubei province and detection of F. hepatica and F. gigantica in Anhui province. The present study of Hubei province shows that mass treatment of livestock with closantel sodium injections in April and August/September controlled Fasciola infection effectively.
Hand, foot and mouth disease (HFMD) is an infectious disease caused by enteroviruses, which usually occurs in children aged <5 years. In China, the HFMD situation is worsening, with increasing number of cases nationwide. Therefore, monitoring and predicting HFMD incidence are urgently needed to make control measures more effective. In this study, we applied an autoregressive integrated moving average (ARIMA) model to forecast HFMD incidence in Sichuan province, China. HFMD infection data from January 2010 to June 2014 were used to fit the ARIMA model. The coefficient of determination (R2), normalized Bayesian Information Criterion (BIC) and mean absolute percentage of error (MAPE) were used to evaluate the goodness-of-fit of the constructed models. The fitted ARIMA model was applied to forecast the incidence of HMFD from April to June 2014. The goodness-of-fit test generated the optimum general multiplicative seasonal ARIMA (1,0,1) × (0,1,0)12 model (R2 = 0·692, MAPE = 15·982, BIC = 5·265), which also showed non-significant autocorrelations in the residuals of the model (P = 0·893). The forecast incidence values of the ARIMA (1,0,1) × (0,1,0)12 model from July to December 2014 were 4103–9987, which were proximate forecasts. The ARIMA model could be applied to forecast HMFD incidence trend and provide support for HMFD prevention and control. Further observations should be carried out continually into the time sequence, and the parameters of the models could be adjusted because HMFD incidence will not be absolutely stationary in the future.
Background: There are no disease modifying agents for the treatment of Alzheimer’s disease (AD). Pathologically, AD is associated with the misfolding of two peptides: beta-amyloid (plaques) and tau (tangles). Methods: Using large-scale computer simulations, we modelled the misfolding of both beta-amyloid and tau, identifying a common conformational motif (CCM; i.e. an abnormal peptide shape), present in both beta-amyloid and tau, that promotes their misfolding. We screened a library of 11.8 million compounds against this in silico model of protein misfolding, identifying three novel molecular classes of putative therapeutics as anti-protein misfolding agents. We synthesized approximately 400 new chemical entity drug-like molecules in each of these three classes (i.e. 1200 potential drug candidates). These were comprehensively screened in a battery of five in vitro protein oligomerization assays. Selected compounds were next evaluated in the APP/PS1 doubly transgenic mouse model of AD. Results: Two new classes of molecules were identified with the ability to block the oligomerization of both beta-amyloid and tau. These compounds are drug-like with good pharmacokinetic properties and are brain-penetrant. They exhibit excellent efficacy in transgenic mouse models. Conclusion: Computer aided drug design has enabled the discovery of novel drug-like molecules able to inhibit both tau and beta-amyloid misfolding.
This study aimed to investigate the long-term efficacy of intratympanic methylprednisolone perfusion treatment for intractable Ménière's disease.
A retrospective analysis of 17 intractable Ménière's disease patients treated with intratympanic methylprednisolone perfusion was performed. Treatment efficacy was evaluated according to the American Academy of Otolaryngology–Head and Neck Surgery criteria. Short and long-term control or improvement rates were calculated after 6 and 24 months, respectively.
Sixteen patients were followed for more than two years. Short- and long-term vertigo control rates were 94 per cent and 81 per cent, respectively; short- and long-term functional activity improvements were 94 per cent and 88 per cent, respectively. The pure tone average was 53 ± 14 dB before treatment, and 50 ± 16 dB at 6 months and 52 ± 20 dB at 24 months after intratympanic methylprednisolone perfusion. Tinnitus was controlled or improved in five patients over the two-year follow-up period.
Intratympanic methylprednisolone perfusion can effectively control vertigo and improve functional activity in intractable Ménière's disease patients with good hearing preservation. It may therefore be a viable alternative treatment for intractable Ménière's disease.
To understand the clinical epidemiology and molecular characteristics of human bocavirus (HBoV) infection in children with diarrhoea in Guangzhou, South China, we collected 1128 faecal specimens from children with diarrhoea from July 2010 to December 2012. HBoV and five other major enteric viruses were examined using real-time polymerase chain reaction. Human rotavirus (HRV) was the most prevalent pathogen, detected in 250 (22·2%) cases, followed by enteric adenovirus (EADV) in 76 (6·7%) cases, human astrovirus (HAstV) in 38 (3·4%) cases, HBoV in 17 (1·5%) cases, sapovirus (SaV) in 14 (1·2%) cases, and norovirus (NoV) in 9 (0·8%) cases. Co-infections were identified in 3·7% of the study population and 23·5% of HBoV-positive specimens. Phylogenetic analysis revealed 14 HBoV strains to be clustered into species HBoV1 with only minor variations among them. Overall, the detection of HBoV appears to partially contribute to the overall detection gap for enteric infections, single HBoV infection rarely results in severe clinical outcomes, and HBoV sequencing data appears to support conserved genomes across strains identified in this study.
We present the results of an approximately 6 100 deg2 104–196 MHz radio sky survey performed with the Murchison Widefield Array during instrument commissioning between 2012 September and 2012 December: the MWACS. The data were taken as meridian drift scans with two different 32-antenna sub-arrays that were available during the commissioning period. The survey covers approximately 20.5 h < RA < 8.5 h, − 58° < Dec < −14°over three frequency bands centred on 119, 150 and 180 MHz, with image resolutions of 6–3 arcmin. The catalogue has 3 arcmin angular resolution and a typical noise level of 40 mJy beam− 1, with reduced sensitivity near the field boundaries and bright sources. We describe the data reduction strategy, based upon mosaicked snapshots, flux density calibration, and source-finding method. We present a catalogue of flux density and spectral index measurements for 14 110 sources, extracted from the mosaic, 1 247 of which are sub-components of complexes of sources.
Soybean is an important oil- and protein-producing crop and over the last few decades soybean genetic transformation has made rapid strides. The probability of occurrence of transgene flow should be assessed, although the discrimination of conventional and transgenic soybean seeds and their hybrid descendants is difficult in fields. The feasibility of non-destructive discrimination of conventional and glyphosate-resistant soybean seeds and their hybrid descendants was examined by a multispectral imaging system combined with chemometric methods. Principal component analysis (PCA), partial least squares discriminant analysis (PLSDA), least squares-support vector machines (LS-SVM) and back propagation neural network (BPNN) methods were applied to classify soybean seeds. The current results demonstrated that clear differences among conventional and glyphosate-resistant soybean seeds and their hybrid descendants could be easily visualized and an excellent classification (98% with BPNN model) could be achieved. It was concluded that multispectral imaging together with chemometric methods would be a promising technique to identify transgenic soybean seeds with high efficiency.
The transmission of haemorrhagic fever with renal syndrome (HFRS) is deeply influenced by the reservoir and hantavirus prevalence rate. In this study, a surveillance on human HFRS cases, relative rodent abundance, and hantavirus infection prevalence was conducted in Shaanxi province, China, during 1984–2012. A generalized linear model with Poisson-distributed residuals and a log link was used to quantify the relationship between reservoir, virus and HFRS cases. The result indicated that there was a significant association of HFRS incidence with relative rodent density and the prevalence rate. This research provides evidence that the changes of infection prevalence in the reservoir could lead directly to the emergence of a new epidemic. It was concluded that the measurement of a number of these variables could be used in disease surveillance to give useful advance warning of potential disease epidemics.
In this study, epidemiological factors of sparganosis cases reported in mainland China from 1959 to December 2012 were analysed. A total of 1061 valid cases were distributed throughout most of the provinces of mainland China, with most cases occurring in Southern and Eastern China. The average age of patients was 29 years (range 0–80 years). Modes of transmission to humans were via contact (54·6%), mainly by application of frog meat as a poultice, foodborne (33·8%), mainly through ingesting frogs or snakes, and waterborne (11·5%) through drinking raw water. The tissue/organs involved were subcutaneous/muscle (43·1%), eyes (31·0%), central nervous system (CNS) (17·9%), urogenital system (3·9%) and visceral organs (3·2%). Obvious differences existed in main risk factors for different areas. Close correlation was found between tissue/organs and risk factors. Main modes of transmission changed during the past decades, from contact (83·8% pre-1979) to foodborne (63·9% post-2000). The tissue/organs involved also changed at the same time. Cases involving eyes fell from 50·0% pre-1979 to 8·3% post-2000, and cases involving CNS increased from 0% pre-1979 to 47·8% post-2000. These results illustrate that China is one of the main epidemic countries of sparganosis in the world. Consumption of frog/snake meat was the main risk factor, although application of frog flesh as a poultice was the main risk factor before 2000. Sparganosis has become one of the neglected but important foodborne/waterborne parasitic diseases in mainland China.
Differentiating bipolar from recurrent unipolar depression is a major clinical challenge. In 18 healthy females and 36 females in a depressive episode – 18 with bipolar disorder type I, 18 with recurrent unipolar depression – we applied pattern recognition analysis using subdivisions of anterior cingulate cortex (ACC) blood flow at rest, measured with arterial spin labelling. Subgenual ACC blood flow classified unipolar v. bipolar depression with 81% accuracy (83% sensitivity, 78% specificity).
The influence of Zn on the adsorption and desorption of Cry1Ab toxin from Bacillus thuringiensis (Bt) on palygorskite and montmorillonite was studied. The adsorption of the toxin gradually increased with increasing Zn concentration from 0 to 1.0 mmol L–1, and then decreased with further increase in Zn concentration. The adsorption isotherms of the toxin in the absence and presence of Zn were well described by the Langmuir equation (R2 > 0.9810–0.9991). The separation factor (RL) decreased with increase of Zn concentration, suggesting that the irreversibility of the adsorption increases. The XRD results showed that the treatment by Tris buffer or Zn(NO3)2 solution caused an expansion of the interlayer space of montmorillonite but did not affect palygorskite. The IR spectra suggest that Zn was likely to be combined with amino groups on the surface of the toxin. The presence of Zn during the adsorption of the toxin decreased desorption, suggesting that the residual risk of toxin would be exacerbated if soil is polluted by zinc.