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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.
This study aimed to evaluate the transcriptional changes occurring in isolated perfused mammary alveolar tissue in response to inoculation with S. agalactiae and to identify the most affected biological functions and pathways after 3 h. Four udders taken at slaughter from cows with healthy mammary gland were perfused ex situ with warmed and gassed Tyrode's solution. Mammary alveolar tissue samples were taken from the left fore and rear quarters (IQ-inoculated quarters) before inoculation (hour 0) and at 3 h post inoculation (hpi) and at the same times from control right fore and rear quarters (not inoculated: NIQ). A total of 1756 differentially expressed genes (DEGs) were identified between IQ and NIQ at 3 hpi using edgeR package. Within this set of DEGs, 952 were up regulated and mainly involved with innate immune response and inflammatory response, e.g., CD14, CCL5, TLR2, IL-8, SAA3, as well as in transcriptional regulation such as FOS, STAT3 and NFKBIA. Genes down-regulated (804) included those involved with lipid synthesis e.g., APOC2, SCD, FABP3 and FABP4. The most affected pathways were chemokine signaling, Wnt signaling and complement and coagulation cascades, which likely reflects the early stage response of mammary tissue to S. agalactiae infection. No significant gene expression changes were detected by RNA-Seq in the others contrasts. Real time-PCR confirmed the increase in mRNA abundance of immune-related genes: TLR2, TLR4, IL-1β, and IL-10 at 3 hpi between IQ and NIQ. The expression profiles of Casp1 and Bax for any contrasts were unaffected whereas Bcl2 was increased in IQ, which suggests no induction of apoptosis during the first hours after infection. Results provided novel information regarding the early functional pathways and gene network that orchestrate innate immune responses to S. agalactiae infection. This knowledge could contribute to new strategies to enhance resistance to this disease, such as genomic selection.
In recent years, mobile robots have become increasingly frequent in daily life applications, such as cleaning, surveillance, support for the elderly and people with disabilities, as well as hazardous activities. However, a big challenge arises when the robotic system must perform a fully autonomous mission. The main problems of autonomous missions include path planning, localisation, and mapping. Thus, this research proposes a hybrid methodology for mobile robots on an autonomous mission involving an offline approach that uses the Direct-DRRT* algorithm and the artificial potential fields algorithm as the online planner. The experimental design covers three scenarios with an increasing degree of accuracy in respect of the real world. Additionally, an extensive evaluation of the proposed methodology is reported.
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.
To compare the accuracy of Mini-Mental State Examination (MMSE) and of the Montreal Cognitive Assessment (MoCA) in tracking mild cognitive impairment (MCI) and Alzheimer’s Disease (AD).
A Systematic review of the PubMed, Bireme, Science Direct, Cochrane Library, and PsycInfo databases was conducted. Using inclusion and exclusion criteria and staring with 1,629 articles, 34 articles were selected. The quality of the selected research was evaluated through the Quality Assessment of Diagnostic Accuracy Studies 2 tool (QUADAS-2).
More than 80% of the articles showed MoCA to be superior to MMSE in discriminating between individuals with mild cognitive impairment and no cognitive impairment. The area under the curve varied from 0.71 to 0.99 for MoCA, and 0.43 to 0.94 for MMSE, when evaluating the ability to discriminate MCI in the cognitively healthy elderly individuals, and 0.87 to 0.99 and 0.67 to 0.99, respectively, when evaluating the detection of AD. The AUC mean value for MoCA was significantly larger compared to the MMSE in discriminating MCI from control [0.883 (CI 95% 0.855-0.912) vs MMSE 0.780 (CI 95% 0.740-0.820) p < 0.001].
The screening tool MoCA is superior to MMSE in the identification of MCI, and both tests were found to be accurate in the detection of AD.
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.
Tuberculosis (TB) is still a major public health problem in many countries, including Brazil. Primary health care (PHC) services are a set of important services with infrastructure and resources to diagnose, treat, and cure several diseases, including the TB.
The aim of this study is to analyse aspects of the facility infrastructure of Brazilian PHC, regarding the control and treatment of TB from a countrywide perspective.
This is a cross-sectional study based on PHC services. Data were collected from 38,812 health centres and were assessed by means of the National Program for Improving Access and Quality Primary Care. The outcome was obtained by the presence and availability of the following infrastructure items: air circulation in the consultation room, refrigerator, individual protective equipment, plastic jar for sputum examination, and TB notification form of the primary care information system. Poisson regression was used to calculate the prevalence ratio.
Of the 38,812 evaluated centres, only 1628 (4.2%) presented a positive result regarding the outcome. Primary health centres, among all types of centres, presented the highest quality of facility infrastructure for TB control. Centres with large workloads, as well as those that presented a list of offered services and a welcoming consulting room, also presented the highest quality infrastructure. The present study shows that major improvements should be made to the infrastructure to reach a satisfactory TB control in Brazil.
The National Institute of Mental Health launched the Research Domain Criteria (RDoC) initiative to better understand dimensions of behavior and identify targets for treatment. Examining dimensions across psychiatric illnesses has proven challenging, as reliable behavioral paradigms that are known to engage specific neural circuits and translate across diagnostic populations are scarce. Delay discounting paradigms seem to be an exception: they are useful for understanding links between neural systems and behavior in healthy individuals, with potential for assessing how these mechanisms go awry in psychiatric illnesses. This article reviews relevant literature on delay discounting (or the rate at which the value of a reward decreases as the delay to receipt increases) in humans, including methods for examining it, its putative neural mechanisms, and its application in psychiatric research. There exist rigorous and reproducible paradigms to evaluate delay discounting, standard methods for calculating discount rate, and known neural systems probed by these paradigms. Abnormalities in discounting have been associated with psychopathology ranging from addiction (with steep discount rates indicating relative preference for immediate rewards) to anorexia nervosa (with shallow discount rates indicating preference for future rewards). The latest research suggests that delay discounting can be manipulated in the laboratory. Extensively studied in cognitive neuroscience, delay discounting assesses a dimension of behavior that is important for decision-making and is linked to neural substrates and to psychopathology. The question now is whether manipulating delay discounting can yield clinically significant changes in behavior that promote health. If so, then delay discounting could deliver on the RDoC promise.
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.
Introduction: Seeking patient outcome feedback (POF), defined as obtaining information on a patients clinical course beyond ones care, is crucial to the learning process. However, the lack of POF is a major pitfall of emergency medicine. Emergency department (ED) bouncebacks, which are characterized as patients with unplanned returns to the ED after being discharged, are an important type of POF to study because they represent a potential misdiagnosis or mismanagement and can highlight areas for physician self-improvement. Currently, most hospitals do not relay details about ED bouncebacks back to the treating physician, unless a grave error occurred. This studys purpose is to provide weekly reports to all physicians in the ED on patients who have unplanned returns within 7 days of discharge from the ED, and evaluate the impact this has on the physicians practice on seeking POF. Methods: A new weekly report was distributed to physicians working at an academic hospital outlining the patients who have returned within 7 days of discharge from the ED, their new presenting complaint and final disposition. An online survey was also administered to all ED staff evaluating the amount of POF they sought pre and post report, and their attitude towards the new reports. Results: 22 responses were received, for a response rate of 85%. The majority of respondents follow the reports (73%) and actively seek POF by looking up patients charts and results(70%). Additionally, 58% state that they seek POF more often since receiving these reports, for both the bouncebacks and their other patients. Furthermore, 37% claimed that the reports helped improve the appropriateness of their referrals and 32% stated it helped increase their confidence in their clinical practice. The majority of physicians (87%) found the reports to be helpful and would like to continue receiving it. Conclusion: Weekly bounceback reports are a high-yield tool for increasing POF sought in the ED and have benefits for both the physician and the department as a whole. They can be used to not only identify patients who may have had an error in their management, but also help to improve physicians’ clinical skills by encouraging and enabling follow-up of patients they managed. Thus, bounceback reports are a valuable tool to provide to physicians and should be considered by ED Departments.
By using quasi-optical tools, it is possible to approximate microwave radiation to Gaussian beams, which enables the study of its propagation and coupling to different components. Hence, their usefulness for wireless power transfer and rapid system design. In this paper, a system composed of two reflectors is analyzed both theoretically and by discussing two cases where quasi-optical tools were applied. The near- and far-field regimes were considered and corresponding frequencies of operation, beam radius, and radius of curvature were computed.
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.
Twin studies have found that ~50% of variance in electrocardiogram (ECG) traits can be explained by genetic factors. However, genetic variants identified through genome-wide association studies explain less than 10% of the total trait variability. Some have argued that the equal environment assumption for the classical twin model might be invalid, resulting in inflated narrow-sense heritability (h2) estimates, thus explaining part of the ‘missing h2’. Genomic relatedness restricted maximum likelihood (GREML) estimation overcomes this issue. This method uses both family data and genome-wide coverage of common SNPs to determine the degree of relatedness between individuals to estimate both h2 explained by common SNPs and total h2. The aim of the current study is to characterize more reliably than previously possible ECG trait h2 using GREML estimation, and to compare these outcomes to those of the classical twin model. We analyzed ECG traits (heart rate, PR interval, QRS duration, RV5+SV1, QTc interval, Sokolow-Lyon product, and Cornell product) in up to 3,133 twins from the TwinsUK cohort and derived h2 estimates by both methods. GREML yielded h2 estimates between 47% and 68%. Classical twin modeling provided similar h2 estimates, except for the Cornell product, for which the best fit included no genetic factors. We found no evidence that the classical twin model leads to inflated h2 estimates. Therefore, our study confirms the validity of the equal environment assumption for monozygotic and dizygotic twins and supports the robust basis for future studies exploring genetic variants responsible for the variance of ECG traits.
This study evaluates the morbidity, mortality, and cost differences between patients who underwent either a simple or a complex arterial switch operation.
A retrospective study of patients undergoing an arterial switch operation at a single institution was performed. Simple cases were defined as patients with d-transposition of the great arteries with usual coronary anatomy or circumflex artery originating from the right with either intact ventricular septum or ventricular septal defect. Complex cases included all other forms of coronary anatomy, aortic coarctation or arch hypoplasia, and Taussig–Bing anomalies. Costs were acquired using an institutional activity-based accounting system.
A total of 98 patients were identified, 68 patients in the simple group and 30 in the complex group. The mortality rate was 2% for the simple and 7% for the complex group, p=0.23. Major morbidities including cardiac arrest, extracorporeal membrane oxygenation, a major coronary event, surgical or catheter-based re-intervention, stroke, or permanent pacemaker placement, non-cardiac surgical procedures, mediastinitis, and sepsis did not differ between the simple and complex groups (16 versus 27%, p=0.16). The complex group had increased bleeding requiring re-exploration (0 versus 10%, p=0.04). Hospital and ICU length of stay did not differ. Complex patients had higher overall hospital costs (simple $80,749 versus complex $97,387, p=0.01) and higher postoperative costs (simple $60,192 versus complex $70,132, p=0.02). The operating room and supplies accounted for the majority of the cost difference.
Complex arterial switches can be safely performed with low rates of morbidity and mortality but at an increased cost.
While increasing trade and foreign direct investment, international trade agreements create winners and losers. Our paper examines the distributional consequences of preferential trade agreements (PTAs) at the firm level. We contend that PTAs expand trade among the largest and most productive multinationals by lowering preferential tariffs. We examine data covering the near universe of US foreign direct investment and disaggregated tariff data from PTAs signed by the United States. Our results indicate that US preferential tariffs increase sales to the United States from the most competitive subsidiaries of multinational corporations operating in partner countries. We also find increases in market concentration in partner countries following preferential liberalization with the United States. By demonstrating that the gains from preferential liberalization are unevenly distributed across firms, we shed new light on the firm-level, economic sources of political mobilization over international trade and investment policies.
Low heart rate variability (HRV) predicts sudden cardiac death. Long-chain (LC) n-3 PUFA (C20–C22) status is positively associated with HRV. This cross-sectional study investigated whether vegans aged 40–70 years (n 23), whose diets are naturally free from EPA (20 : 5n-3) and DHA (22 : 6n-3), have lower HRV compared with omnivores (n 24). Proportions of LC n-3 PUFA in erythrocyte membranes, plasma fatty acids and concentrations of plasma LC n-3 PUFA-derived lipid mediators were significantly lower in vegans. Day-time interbeat intervals (IBI), adjusted for physical activity, age, BMI and sex, were significantly shorter in vegans compared with omnivores (mean difference −67 ms; 95 % CI −130, −3·4, P<0·05), but there were no significant differences over 24 h or during sleep. Vegans had higher overall HRV, measured as 24 h standard deviation of normal-to-normal intervals (SDNN) (mean adjusted difference 27 ms; 95 % CI 1, 52, P=0·039). Conversely, vegans presented with decreased 8 h day-time HRV: mean adjusted difference in SDNN −20 ms; 95 % CI −37, −3, P=0·021, with no differences during nocturnal sleep. Day-time parameters of beat-to-beat HRV (root of the mean of the sum of the squares of differences between adjacent normal-to-normal intervals, percentage of adjacent normal-to-normal intervals that differ by >50 % and high-frequency power) were similarly lower in vegans, with no differences during sleep. In conclusion, vegans have higher 24 h SDNN, but lower day-time HRV and shorter day-time IBI relative to comparable omnivores. Vegans may have reduced availability of precursor markers for pro-resolving lipid mediators; it remains to be determined whether there is a direct link with impaired cardiac function in populations with low-n-3 status.