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Various host and parasite factors interact to determine the outcome of infection. We investigated the effects of two factors on the within-host dynamics of malaria in mice: initial infectious dose and co-infection with a helminth that limits the availability of red blood cells (RBCs). Using a statistical, time-series approach to model the within-host ‘epidemiology’ of malaria, we found that increasing initial dose reduced the time to peak cell-to-cell parasite propagation, but also reduced its magnitude, while helminth co-infection delayed peak cell-to-cell propagation, except at the highest malaria doses. Using a mechanistic model of within-host infection dynamics, we identified dose-dependence in parameters describing host responses to malaria infection and uncovered a plausible explanation of the observed differences in single vs co-infections. Specifically, in co-infections, our model predicted a higher background death rate of RBCs. However, at the highest dose, when intraspecific competition between malaria parasites would be highest, these effects of co-infection were not observed. Such interactions between initial dose and co-infection, although difficult to predict a priori, are key to understanding variation in the severity of disease experienced by hosts and could inform studies of malaria transmission dynamics in nature, where co-infection and low doses are the norm.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
Takeaway shops are more clustered around secondary than primary schools and UK planning policies to limit takeaways show poor implementation against international examples and good practice statements. A major concern is that, worldwide, there are no standardised measures used to measure the food environment around homes, schools, work or any other facilities. This study aims to examine the differences in using different methods to evaluate the food environment particularly around secondary schools in the Avon region in the UK. Geographical Information System (GIS) was used to locate all schools and takeaways in the region and to measure the density and proximity scores, applying both road network and straight-line methods. In addition, the Hansen Index was used to measure the accessibility score of each schools to all takeaways in the region (not just the nearest). All of the nonparametric statistical analysis tests including Wilcoxon test, agreement (Kappa statistic) test and correlation test were carried out using Stata software version 15.0. It was observed that more than 50% of the schools had no takeaway shops within 200, 400, and 600 metres when the road network buffer was used. Statistical differences were observed between the road network and the straight-line methods. For example, the median of the difference between the straight-line and road network density within 1000 metres was 4.1 (CI 2.6, 5.9; P < 0.001). The median of the difference between the road network and straight-line proximity was 203.2 (CI 144.6, 261.9; P < 0.001). Also, the agreement between straight-line and road network densities within 800 (Kappa = 0.38) and 1000 (Kappa = 0.47) metres were fair and moderate, respectively. The agreement between both methods to measure the proximity was fair to moderate (Kappa = 0.40). In addition, the correlation results showed that both the straight-line and road network proximity were negatively correlated to the accessibility score measured. Our findings suggest that the 800 and 1000 metres road network density and proximity may be more appropriate to explore the real relationships between fast food accessibility and diet or health relationships. In addition, the Hansen index is another metric that may be used if the aim of the study is to consider multiple locations when calculating the accessibility score. The availability of best-practice methods would help to explore the food environment in a consistent way and therefore lead to the implementation of effective actions and policies targeting the food environments, particularly around secondary schools.
The effects of fish oil (FO) supplementation on glycaemic control are unclear, and positive effects may occur only when the phospholipid content of tissue membranes exceeds 14 % as n-3 PUFA. Subjects (n 36, thirty-three completed) were paired based on metabolic parameters and allocated into a parallel double-blind randomised trial with one of each pair offered daily either 6 g of FO (3·9 g n-3 PUFA) or 6 g of maize oil (MO) for 9 months. Hyperinsulinaemic–euglycaemic–euaminoacidaemic (HIEGEAA) clamps (with [6,6 2H2 glucose]) were performed at the start and end of the intervention. Endogenous glucose production (EGP) and whole-body protein turnover (WBPT) were each measured after an overnight fast. The primary outcome involved the effect of oil type on insulin sensitivity related to glycaemic control. The secondary outcome involved the effect of oil type on WBPT. Subjects on FO (n 16) had increased erythrocyte n-3 PUFA concentrations >14 %, whereas subjects on MO (n 17) had unaltered n-3 PUFA concentrations at 9 %. Type of oil had no effect on fasting EGP, insulin sensitivity or total glucose disposal during the HIEGEAA clamp. In contrast, under insulin-stimulated conditions, total protein disposal (P=0·007) and endogenous WBPT (P=0·001) were both increased with FO. In an associated pilot study (n 4, three completed), although n-3 PUFA in erythrocyte membranes increased to >14 % with the FO supplement, the enrichment in muscle membranes remained lower (8 %; P<0·001). In conclusion, long-term supplementation with FO, at amounts near the safety limits set by regulatory authorities in Europe and the USA, did not alter glycaemic control but did have an impact on WBPT.
Mounting an antibody response capable of discriminating amongst and appropriately targeting different parasites is crucial in host defence. However, cross-reactive antibodies that recognize (bind to) multiple parasite species are well documented. We aimed to determine if a higher inoculating dose of one species, and thus exposure to larger amounts of antigen over a longer period of time, would fine-tune responses to that species and reduce cross-reactivity. Using the Plasmodium chabaudi chabaudi (Pcc)–Nippostrongylus brasiliensis (Nb) co-infection model in BALB/c mice, in which we previously documented cross-reactive antibodies, we manipulated the inoculating dose of Pcc across 4 orders of magnitude. We investigated antigen-specific and cross-reactive antibody responses against crude and defined recombinant antigens by enzyme linked immunosorbent assay, Western blot and antibody depletion assays. Contrary to our hypothesis that increasing exposure to Pcc would reduce cross-reactivity to Nb, we found evidence for increased avidity of a subpopulation of antibodies that recognized shared antigens. Western blot indicated proteins of apparent monomer molecular mass 28 and 98 kDa in both Nb and Pcc antigen preparations and also an Nb protein of similar size to recombinant Pcc antigen, merozoite surface protein-119. The implications of antibodies binding antigen from such phylogenetically distinct parasites are discussed.
The School Fruit and Vegetable Scheme (SFVS) provides children in government-run schools in England with a free piece of fruit or a vegetable each school day for the first 3 years of school. The present study examines the impact of the SFVS, in terms of its contribution towards the total daily intake of fruit and vegetables by children across England. Quantitative dietary data were collected from 2306 children in their third year of school, from 128 schools, using a 24 h food diary. The data were examined at different spatial scales, and variations in the impact of the scheme across areas with different socio-economic characteristics were analysed using a deprivation index and a geodemographic classification. The uptake of the SFVS and the total intake of fruit and vegetables by children varied across different parts of England. Participation in the SFVS was positively associated with fruit and vegetable consumption. That is, in any one area, those children who participated in the SFVS consumed more fruit and vegetables. However, children living in deprived areas still consumed less fruit and vegetables than children living in more advantaged areas: the mean daily frequency of fruit and vegetables consumed, and rates of consumption of fruit or vegetables five times or more per d, decreased as deprivation increased (r − 0·860; P = 0·001; r − 0·842; P = 0·002). So the SFVS does not eliminate the socio-economic gradient in fruit and vegetable consumption, but it does help to increase fruit and vegetable consumption in deprived (and affluent) areas.
To monitor growth trends in young children in order to ascertain success (or otherwise) in halting the rapid rise in childhood obesity prevalence, and to assess the suitability of using routinely measured data for this purpose.
Design
Retrospective serial cross-sectional analyses of the proportion of obese children (logistic regression) and BMI standard deviation score (linear regression/maps) were undertaken. BMI coverage was calculated as percentage of sample with data (‘usual’), percentage of total births and percentage of census values. BMI was standardised for age and sex (British reference data set).
Setting
Metropolitan Leeds, UK.
Subjects
Children aged 3 to 6 years. Weight, height, sex, age and postcode data were collected from Primary Care Trust records.
Results
Data were collected on 42 396 children, of whom 13 020 (31 %) were excluded due to missing data/data problems. Seventy-two per cent of 3-year-olds and 92 % of 5-year-olds had data recorded (‘usual’ coverage). From 1998 to 2003 there was a significant increase in the proportion of obese children (4·5 % to 6·6 %; P < 0·001); children were 1·5 times more likely to be obese in 2003 than in 1998.
Conclusions
Childhood obesity rose significantly between 1998 and 2003. Routinely measured data are an important means of monitoring population-level obesity trends, although more effort is required to reduce the quantity of data-entry errors, for relatively low marginal cost.
Smoking is one of the major causes of premature death and its negative effects on a person's health are a global issue. Therefore, the United Kingdom has introduced new policies aimed at reducing the proportion of smokers from 26% in 2005 down to 21% by 2010. One mechanism to meet this policy target is the provision of stop smoking services. This article aims to estimate the Leeds smoking population at the small area level and especially to highlight the distribution of hard-to-reach groups such as heavy smokers (> 20 cigarettes/day) and pregnant women who smoke. Then optimal location strategies are discussed in relation to stop smoking services. The findings show the importance of adding a spatial component to find out where the smoking population or specific subgroups of smokers are to support policymakers or healthcare planners who are responsible for the planning process of the services.
The requirement for accuracy in the counting of somatic cells in milk has been increased by the use of this measurement as a basis of payment for milk. This paper reports on several factors that can substantially affect efficiency of staining and cell detection in various types of fluorescent cell counters. These mordant factors include sample age, chemical preservative, other sample preservation treatments and reagent properties. Experiments were conducted in several laboratories with Fossomatic 215 and 360 cell counting instruments to measure the effect of these mordant factors on both cell fluorescence and cell count. Counting efficiency was as low as 20% for some instruments counting some particular samples, depending upon the combination of adverse mordant factors. The problem of poor counting efficiency was also not detected by calibration samples that had more favourable mordant treatments applied. The adverse mordant factors were shown to reduce the intensity of fluorescence of cells for all instruments. We suggest that a significant reduction in counting efficiency due to these adverse mordant factors is most likely to occur when the particular instrument already has an intrinsic inability to separate cell fluorescence properly from background noise. This paper also discusses quality control samples, the impact of various factors on discriminator curves and the use of appropriate measures to maintain good calibration adjustment.
Plantation Farm, Shippea Hill, is situated in the south-east corner of the Fenland, some seven miles ENE. of Ely. The vast Fenland plain, formed essentially by the filling-up of a corrugated basin of Jurassic and boulder clays with post-glacial peats, silts, and clays, provides a field for the study of post-glacial changes of environment in relation to man without equal in Britain. As reported in a recent number of the Antiquaries Journal, a Research Committee has been formed at Cambridge under the presidency of Dr. Seward, F.R.S., to organize research in this work and to secure adequate co-operation of specialists in the different sciences. Notwithstanding great advances in the technical equipment of research, remarkably little has been added to our knowledge in this field since the publication of Skertchley's Geology of the Fenland in 1877. We have had, therefore, to begin at the beginning, and this report, which establishes the stratigraphical context of the Early Bronze Age in the deposits of the south-eastern fens, represents one of the first-fruits of our activities. Sir Charles Hiam very kindly allowed us to work on his land, and the Trustees of the Percy Sladen Memorial Fund generously made the excavations and borings possible. We may also take the opportunity here of thanking Mr. Charles Leaf for his part in the initial discovery of the site.
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