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Recent years have seen an exponential increase in the variety of healthcare data captured across numerous sources. However, mechanisms to leverage these data sources to support scientific investigation have remained limited. In 2013 the Pediatric Heart Network (PHN), funded by the National Heart, Lung, and Blood Institute, developed the Integrated CARdiac Data and Outcomes (iCARD) Collaborative with the goals of leveraging available data sources to aid in efficiently planning and conducting PHN studies; supporting integration of PHN data with other sources to foster novel research otherwise not possible; and mentoring young investigators in these areas. This review describes lessons learned through the development of iCARD, initial efforts and scientific output, challenges, and future directions. This information can aid in the use and optimisation of data integration methodologies across other research networks and organisations.
Hermaphroditism is thought to be an advantageous strategy common in marine molluscs that exhibit simultaneous, sequential or alternating hermaphroditism. Several species of patellid limpets have previously been shown to be protandrous hermaphrodites. The present study aimed to confirm whether this phenomenon occurs in Patella piperata. Transitional forms of simultaneous protandrous hermaphroditism were found in intermediate size classes of P. piperata, in Madeira (North-eastern Atlantic). Sequential hermaphroditism was confirmed after histological analysis. The overall sex-ratio was biased towards females but approached similar proportions in the larger size classes. Analysis of size at sex change showed that at a shell length of 36 mm 50% of the population probably have changed sex. The results reported confirm the occurrence of sequential hermaphroditism. These findings are of utmost importance to the understanding of the reproductive biology of this species with direct effect on management and conservation of this traditionally harvested limpet.
The eastern North Atlantic (ENA) has many highly productive areas where several species of cetaceans have been recorded, with the common dolphin (Delphinus delphis) being one of the most frequently sighted species. However, its spatial and temporal distribution in high seas is poorly known. The study presents the results from 5 years of cetacean monitoring in the ENA (2012–2016) aboard cargo ships that follow the routes from Continental Portugal to the Macaronesian archipelagos and north-west Africa. Common dolphin was the most frequently sighted cetacean with 192 occurrences registered on effort and an overall encounter rate of 0.36 sightings/100 nmi. The species was distributed in coastal and offshore waters, but absent from the Canaries and Cape Verde islands. Statistical ‘habitat’ models were developed to describe and explain the occurrence of sightings of the species: variables affecting detection of dolphins had a small impact and there were clear spatiotemporal distribution patterns, influenced to some degree by environmental variables. Predicted probability of occurrence was highest in coastal waters of continental Portugal and around the Azores. The models, combined with maps of distribution, were useful to identify important areas for the species, which could be the focus of future conservation efforts. Common dolphin presence was related to depth, distance to coast and seamounts, seabed slope, chlorophyll concentration, sea-surface temperature and sea level anomalies; the possible ecological significance of these relationships is explored.
Many economic losses occur in the poultry industry due to leg fragility. Knowing the genomic regions that influence traits associated with the growth and composition of the leg’s bone can help to improve the selection process leading to increased leg resistance to fracture. The present study aimed to map quantitative trait loci (QTL) for mineral composition and morphometric traits of the tibia in 478 animals from an F2 broiler × layer cross. The measurement of weight, length and width of Tibia was carried out at 42 days of age. Ash, dry matter, levels of calcium (Ca), phosphorus (P), magnesium (Mg), Zinc (Zn) and Calcium:Phosphorus (Ca:P) ratio were also recorded. The population was genotyped for 128 microsatellite markers and one single nucleotide polymorphism, covering 2630 cM of the chicken genome. A likelihood ratio test was performed to find QTLs. Additive and dominance effects of the QTLs were included in the model. In the chromosomes 2 (GGA2), 6 (GGA6), 8 (GGA8), 24 (GGA24) and 26 (GGA26) some suggestive QTLs (P<0.00276) were mapped for tibia weight (GGA2 and GGA26), ash percentage (GGA2 and GGA6), dry matter percentage (GGA2), Ca (GGA8 and GGA24) and Ca:P ratio (GGA8), many of which are close to genes already identified as good candidates for those traits. The suggestive QTL on GGA2 has a pleiotropic effect on ash percentage, dry matter and bone weight, whereas in the GGA8 there seems to be two QTLs, one for Ca and another for Ca:P ratio. Thus, this study identified at least five genomic regions, in different chromosomes, that can be targeted for further research to identify potential mutations influencing the development and composition of leg bones in Gallus gallus.
Intake, digestibility, nitrogen (N) balance, microbial protein synthesis, weight gain, yields of the main commercial cuts and carcass morphometric measurements were evaluated in lambs fed diets containing different levels of chitosan. Sixty Santa Inês crossbred sheep with an average body weight (BW) of 24 ± 2.2 kg were assigned to three treatments (diets containing 0, 136 or 272 mg chitosan/kg BW) in a completely randomized design. There was no effect of chitosan on dry matter (DM) intake. Ingested and retained N showed a quadratic response, with the highest values estimated at the chitosan levels of 142 and 152 mg/kg BW, respectively. Similar to N balance, microbial protein synthesis showed the same quadratic response, in which the level of 136 mg/kg BW resulted in higher synthesis when compared with the other levels. No effect of chitosan was detected on average daily gain, final weight, or carcass variables (hot carcass weight, cold carcass weight, yield of commercial cuts and morphometric measurements of the carcass). Conformation, visceral fat content and fatness of carcasses were also not altered by the use of chitosan. Chitosan improves the digestibility of DM, crude protein and neutral detergent fibre, and increases N balance and microbial protein synthesis but does not change the production performance of feedlot lambs.
The goal of this study was to analyse the spatial pattern of tuberculosis (TB) mortality using different approaches, namely: mortality rates (MR), spatial relative risks (RR) and Bayesian rates (Global and Local) and their association with human development index (HDI), Global and its three dimensions: education, longevity and income. An ecological study was developed in Curitiba, Brazil based on data from Mortality Information System (2008–2014). Spatial scan statistics were used to compute RR and identify high-risk clusters. Bivariate Local Indicator of Spatial Associations was used to assess associations. MR ranged between 0 and 25.24/100.000 with a mean (standard deviation) of 1.07 (2.66). Corresponding values for spatial RR were 0–27.46, 1.2 (2.99) and for Bayesian rates (Global and Local) were 0.49–1.66, 0.90 (0.19) and 0–6.59, 0.98 (0.80). High-risk clusters were identified for all variables, except for HDI-income and Global Bayesian rate. Significant negative spatial relations were found between MR and income; between RR and HDI global, longevity and income; and Bayesian rates with all variables. Some areas presented different patterns: low social development/low risk and high risk/high development. These results demonstrate that social development variables should be considered, in mortality due TB.
Thiazolidinones present a wide range of useful applications especially in the biological aspect. Based on these facts, the compound of interest 2-(α-naphthyl)-3-(α-pyridinyl)-1,3-thiazolidine-4-one (C18H14N2OS), was synthesized via multi-component reaction with the aim of obtaining a compound that would show activity against fungi and bacteria. The synthesis of 2-(α-naphthyl)-3-(α-pyridinyl)-1,3-thiazolidine-4-one, was carried out from the respective α-aminopyridine with α-naphthylaldehyde and α-mercaptoacetic acid, under reflux in dry toluene for 8 h, obtaining a solid compound. Molecular characterization of the compound was carried out by infrared spectrometry, mass spectrometry, and nuclear magnetic resonance. The study of the crystallization and the calculation of the unit-cell constants were determined by the technique of X-ray diffraction of polycrystalline samples. It was determined that the compound crystallizes in a monoclinic system with space group P21/c [No. 14] and the constants of the unit cell a = 11.958 (3), b = 9.675 (4), c = 12.661 (4) Å, β = 96.960° (2), V = 1454.01 (Å3).
At birth, when immune responses are insufficient, there begins the development of the defence capability against pathogens. Leptin and adiponectin, adipokines that are present in breast milk, have been shown to play a role in the regulation of immune responses. We report here, for the first time, the influence of in vivo adipokine supplementation on the intestinal immune system in early life. Suckling Wistar rats were daily supplemented with leptin (0·7 μg/kg per d, n 36) or adiponectin (35 μg/kg per d, n 36) during the suckling period. The lymphocyte composition, proliferation and cytokine secretion from mesenteric lymph node lymphocytes (on days 14 and 21), as well as intestinal IgA and IgM concentration (day 21), were evaluated. At day 14, leptin supplementation significantly increased the TCRαβ+ cell proportion in mesenteric lymph nodes, in particular owing to an increase in the TCRαβ+ CD8+ cell population. Moreover, the leptin or adiponectin supplementation promoted the early development CD8+ cells, with adiponectin being the only adipokine capable of enhancing the lymphoproliferative ability at the end of the suckling period. Although leptin decreased intestinal IgA concentration, it had a trophic effect on the intestine in early life. Supplementation of both adipokines modulated the cytokine profile during (day 14) and at the end (day 21) of the suckling period. These results suggest that leptin and adiponectin during suckling play a role in the development of mucosal immunity in early life.
High concentrations of indium (In) and selenium (Se) have been reported in the Neves-Corvo volcanic-hosted massive sulfide deposit, Portugal. The distribution of these ore metals in the deposit is complex as a result of the combined effects of early ore-forming processes and late tectonometamorphic remobilization. The In and Se contents are higher in Cu-rich ore types, and lower in Zn-rich ore types. At the deposit scale, both In and Se correlate positively with Cu, whereas their correlations with Zn are close to zero. This argues for a genetic connection between Cu, In and Se in terms of metal sourcing and precipitation. However, re-distribution and re-concentration of In and Se associated with tectonometamorphic deformation are also processes of major importance for the actual distribution of these metals throughout the whole deposit. Although minor roquesite and other In-bearing phases were recognized, it is clear that most In within the deposit is found incorporated within sphalerite and chalcopyrite. When chalcopyrite and sphalerite coexist, the In content in sphalerite (avg. 1400 ppm) is, on average, 2–3 times higher than in chalcopyrite (avg. 660 ppm). The In content in stannite (avg. 1.3 wt.%) is even higher than in sphalerite, but the overall abundance of stannite is subordinate to either sphalerite or chalcopyrite. Selenium is dispersed widely between many different ore minerals, but galena is the main Se-carrier. On average, the Se content in galena is ~50 times greater than in either chalcopyrite (avg. 610 ppm) or sphalerite (avg. 590 ppm). The copper concentrate produced at Neves-Corvo contains very significant In (+Se) content, well above economic values if the copper smelters recovered it. Moreover, the high In content of sphalerite from some Cu-Zn ores, or associated with shear structures, could possibly justify, in the future, a selective exploitation strategy for the production of an In-rich zinc concentrate.
Cognitive deficits are a core feature of early stages in schizophrenia. However, the extent to which antipsychotic (AP) have a deleterious effect on cognitive performance remains under debate. We aim to investigate whether anticholinergic loadings and dose of AP drugs in first episode of psychosis (FEP) in advanced phase of remission are associated with cognitive impairment and the differences between premorbid intellectual quotient (IQ) subgroups.
Two hundred and sixty-six patients participated. The primary outcomes were cognitive dimensions, dopaminergic/anticholinergic load of AP [in chlorpromazine equivalents (Eq-CPZ) and the Anticholinergic Risk Scale (ARS), respectively].
Impairments in processing speed, verbal memory and global cognition were significantly associated with high Eq-CPZ and verbal impairment with high ARS score. Moreover, this effect was higher in the low IQ subgroup.
Clinicians should be aware of the potential cognitive impairment associated with AP in advanced remission FEP, particularly in lower premorbid IQ patients.
Analysing the stability and adaptation of cultivars to different environments is always necessary before recommending them for planting on large areas. Additive main effects and multiplicative interaction (AMMI) models have been used to analyse genotype-by-environment interactions (G × E). AMMI models require data with homogeneous variance, normal errors and additive effects. However, agronomic data do not always conform to these statistical assumptions. The objective of the present study was to analyse G × E interactions for severity and incidence of grey leaf spot, a foliar disease in maize caused by Cercospora zeae-maydis, using a generalized AMMI model. Data were collected and evaluated for 36 maize cultivars from experiments carried out in nine Brazilian regions in 2010/11 by the Empresa Brasileira de Pesquisa Agropecuária (EMBRAPA – Milho e Sorgo). Only two of three stable genotypes defined by a quasi-likelihood model with a logistic link function could be recommended for their desirable agronomic characteristics. Four growing locations in which the genotypes were stable were identified, but in only one of these was stability associated with very severe grey leaf spot disease. Cultivars adapted to specific locations with low percentage disease severity were also identified.
Animal health surveillance enables the detection and control of animal diseases including zoonoses. Under the EU-FP7 project RISKSUR, a survey was conducted in 11 EU Member States and Switzerland to describe active surveillance components in 2011 managed by the public or private sector and identify gaps and opportunities. Information was collected about hazard, target population, geographical focus, legal obligation, management, surveillance design, risk-based sampling, and multi-hazard surveillance. Two countries were excluded due to incompleteness of data. Most of the 664 components targeted cattle (26·7%), pigs (17·5%) or poultry (16·0%). The most common surveillance objectives were demonstrating freedom from disease (43·8%) and case detection (26·8%). Over half of components applied risk-based sampling (57·1%), but mainly focused on a single population stratum (targeted risk-based) rather than differentiating between risk levels of different strata (stratified risk-based). About a third of components were multi-hazard (37·3%). Both risk-based sampling and multi-hazard surveillance were used more frequently in privately funded components. The study identified several gaps (e.g. lack of systematic documentation, inconsistent application of terminology) and opportunities (e.g. stratified risk-based sampling). The greater flexibility provided by the new EU Animal Health Law means that systematic evaluation of surveillance alternatives will be required to optimize cost-effectiveness.
Clinical manifestations of acute bronchiolitis (AB) vary from minimal disease to severe respiratory failure. The response to respiratory viral infections is possibly influenced by genetic polymorphisms linked to the regulation of the inflammatory response. In the present study, we investigated whether interleukin-8 (IL-8) and interleukin-17 (IL-17) genetic variants are associated with the severity of AB. A group of Brazilian infants hospitalized with AB and a control group (infants with no or mild AB, without hospitalization) were genotyped for four IL-8/IL-17 variations. For replication, we studied an Argentinean population sample of infants with mild and severe AB. IL-8 polymorphism (rs 2227543) and IL-17 (rs2275913) variants showed significant associations with the severity of AB. The effect of the IL-8 variation could be replicated in the Argentinean sample. This finding suggests that IL-8 variations may influence the severity of AB in young infants. Further genetic association studies in low- or middle-income populations are necessary with the aim of expanding knowledge in this area.
The aim of this study was to evaluate the effect of dietary lysine on performance, protein deposition and respiratory chain gene expression in male broilers. A total of 252 Cobb 500 broilers were distributed, in a completely randomized design, into four treatments with seven replicates of nine birds per experimental unit. Experimental treatments consisted of diets based on corn and soybean meal, with four levels of digestible lysine: 1.016%, 1.099%, 1.182% and 1.265%. The increase in the level of digestible lysine in the diet provided higher weight gains, feed efficiency and body protein deposition. Birds fed the lowest level of dietary lysine (1.016%) showed a lower expression of genes such as NADH dehydrogenase subunit I (ND1), cytochrome b (CYTB) and cytochrome c oxidase subunits I (COX I), II (COX II) and III (COX III), displaying the worst performance and body protein deposition. This demonstrates the relationship existing between the expression of the evaluated genes and the performance responses. In conclusion, results indicate that broilers fed diets with higher levels of digestible lysine have increased messenger RNA expression of some genes coded in the mitochondrial electron transport chain (ND1, CYTB, COX I, COX II and COX III). It may be stated that diets with proper levels of digestible lysine, within the ‘ideal protein’ concept, promote the expression of genes, which increases the mitochondrial energy, thereby fostering body protein deposition and the performance of broilers in the starter phase.
We say a graph is (Qn,Qm)-saturated if it is a maximal Qm-free subgraph of the n-dimensional hypercube Qn. A graph is said to be (Qn,Qm)-semi-saturated if it is a subgraph of Qn and adding any edge forms a new copy of Qm. The minimum number of edges a (Qn,Qm)-saturated graph (respectively (Qn,Qm)-semi-saturated graph) can have is denoted by sat(Qn,Qm) (respectively s-sat(Qn,Qm)). We prove that
for fixed m, disproving a conjecture of Santolupo that, when m=2, this limit is 1/4. Further, we show by a different method that sat(Qn, Q2)=O(2n), and that s-sat(Qn, Qm)=O(2n), for fixed m. We also prove the lower bound
We present lithium abundances for nine chromospherically young, kinematically old late-type stars. The data support the interpretation that these objects can be formed during the coalescence of a short-period binary.
Direct communication between the right pulmonary artery and the left atrium is rare. We report a case that was first detected in utero and confirmed by a two-dimensional echocardiographic study performed postnatally. The patient remained asymptomatic, and hence was managed conservatively. The fistula gradually decreased in size and closed spontaneously at 15 months of age. The rarity of the case is discussed.
Cognitive deficits are present from the onset of psychosis and are considered a core feature of the disorder. Increasing evidence suggests that cognitive function is associated with inflammatory processes. This study evaluated the association between cognition and inflammatory biomarkers in first-episode psychosis (FEP), in order to identify cognitive phenotypes from inflammatory expression profiles.
A case-control study of 92 FEP patients and 80 matched controls was used. Neurocognitive assessment, including verbal ability, sustained attention, verbal memory, working memory and executive function, was performed. The expression of pro- and anti-inflammatory mediators of the main intracellular inflammatory pathway was measured in peripheral blood mononuclear cells and plasma.
FEP patients performed worse in all cognitive domains compared to controls and had higher expression of pro-inflammatory mediators and lower expression of anti-inflammatory mediators. In the FEP group, cognition and psychopathology were associated with inflammation. Hierarchical regression analysis showed that association between the anti-inflammatory prostaglandin 15d-PGJ2 and sustained attention on one hand, and COX-2 expression and executive function on the other, were statistically significant.
Our study provides evidence for an association between anti-inflammatory biomarkers and cognition in FEP. The identification of a subgroup of patients based on these measures could be useful to guide treatment programmes by providing tools to select a personalized treatment approach, but longitudinal studies are needed before. In the future, establishment of biomarkers linked to cognition would be useful to monitor the course of cognitive impairment, but substantially more data will be required. Determination of IκBα, the inhibitory protein of the pro-inflammatory transcription factor NFκB, could be useful in early phases to assess clinical severity.
N-3 polyunsaturated fatty acids (PUFAs) have been hypothesised to be protective for depression during pregnancy. However, there are few data and no consensus regarding this association. In this line, we aim to evaluate if the concentration of n-3 and n-6 PUFAs, and their ratio, are associated with depressive symptoms throughout pregnancy.
A prospective cohort of 172 Brazilian women was followed at 5–13th, 20–26th and 30–36th weeks of gestation. The presence of depressive symptoms was evaluated using the Edinburgh Postnatal Depression Scale (EPDS) at each pregnancy trimester. Depression was defined as an EPDS score ≥11. The concentrations of n-3 [α-linolenic acid; eicosapentaenoic acid (EPA); docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA)] and n-6 PUFAs [linoleic acid; γ linolenic acid; eicosadienoic acid; eicosatrienoic acid; arachidonic acid; docosatetraenoic acid and docosapentaenoic acid] were expressed as absolute (μg/ml) values. The total n-6/n-3 ratio was calculated. Statistical analyses were performed using univariate and adjusted random intercept logistic model for each fatty acid (FA) considering the longitudinal nature of data. Covariates were selected as potential confounders based on their biological plausibility of having an association with the concentration of FA and depressive symptoms during pregnancy.
The prevalence of depressive symptoms was high in all pregnancy trimesters (1st = 33.7%; 2nd = 18.9%; 3rd = 17.4%). We did not find differences in means FA concentrations by depressive symptom classification, for each follow-up visit. The women presented a 5% decrease in the odds of having depressive symptoms for each one-week increase in the gestational age. As individual women progressed through pregnancy, higher concentrations of EPA (odds ratio (OR) = 0.92; 95% CI: 0.86–0.99), DHA (OR = 0.96; 95% CI: 0.93–0.99), DPA (OR = 0.87; 95% CI: 0.77–0.99) and total n-3 (OR = 0.98; 95% CI: 0.96–0.99) were associated with a lower odds of depressive symptoms, while higher total n-6/n-3 ratio were associated with greater odds of depressive symptoms (OR = 1.40; 95% CI: 1.09–1.79). We detected a decrease in the probability of depressive symptoms as concentrations of total n-3 FA, α-linolenic acid, DPA, and DHA increased. We also observed a sharper decline for women with initial greater chance of depressive symptoms compared with those with lower chance of having these symptoms.
We found a high prevalence of depressive symptoms in low-income Brazilian pregnant women and no significant associations between n-6 FA and depressive symptoms. Lower serum concentrations of DHA, EPA and DPA and a higher n-6/n-3 ratio at each pregnancy trimester were associated with higher odds of depressive symptoms throughout pregnancy.
Human toxocarosis is a chronic tissue parasitosis most often caused by Toxocara canis. The seroprevalence can reach up to 50%, especially among children and adolescents. The anthelmintics used in the treatment have moderate efficacy. The aim of this study was to evaluate the in vitro and in vivo anthelmintic activity of quinones and their derivatives against T. canis larvae and the cytotoxicity of the larvicidal compounds. The compounds were evaluated at 1 mg mL−1 concentration in microculture plates containing third stage larvae in an Roswell Park Memorial Institute (RPMI) 1640 environment, incubated at 37 °C in 5% CO2 tension for 48 h. Five naphthoxiranes were selected for the cytotoxicity analysis. The cell viability evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays using murine peritoneal macrophages isolated from C57BL/6 mice revealed that the naphthoxiranes (1 and 3) were less cytotoxic at a concentration of 0·05 mg mL−1. The efficacy of naphthoxiranes (1 and 3) was examined in murine toxocarosis also. The anthelmintic activity was examined by evaluating the number of larvae in the brain, carcass, liver, lungs, heart, kidneys and eyes. Compound (3) demonstrated anthelmintic activity similar to that of albendazole by decreasing the number of larvae in the organs of mice and thus could form the basis of the development of a new anthelmintic drug.