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ABSTRACT IMPACT: Human exhaled breath is rich in metabolomic content that represents pulmonary function and gas exchange with blood, which can provide insights into an individual’s state of health. OBJECTIVES/GOALS: Human exhaled breath is rich in metabolomic content that represents pulmonary function and gas exchange with blood. It contains a mixture of compounds that offer insight into an individual’s state of health. Here, we present two novel non-invasive breath sampling devices for use in basic medical practice. METHODS/STUDY POPULATION: The two breath samplers have a disposable mouthpiece, a set of inhale and exhale one-way flap valves to allow condensation of exhaled breath only, and a saliva filter. The housing is constructed out of Teflon®, a chemically inert material to reduce chemical absorbance. The first device condenses exhaled breath into a frozen condensate using dry ice pellets and the other is a miniaturized design that liquifies exhaled breath on a condenser surface with micropatterned features on a cooling plate. Both designs have individual strategic and analytical advantages: frozen exhaled breath condensate (EBC) has high retention of analytes and sample volume; EBC collected in liquid phase offers facilitated sample collection and device portability. RESULTS/ANTICIPATED RESULTS: We investigated if breath aerosol size distribution affects the types or abundances of metabolites. We modified the geometry of the first device to redirect aerosol trajectories based on size. The trapping of larger aerosols increases with filter length, thus altering the aerosol size distribution although no significant changes in the metabolite profiles were found. With the miniaturized device, metabolite abundances were measured in a small cohort of healthy control and mild asthmatic subjects. Differences among subjects were found, as well as main differences between control and asthmatic groups. All analyses of EBC were performed with liquid chromatography - mass spectrometry. Inflammatory suppression found in asthmatic subjects can be explained by prescribed daily use of inhaled corticosteroids. DISCUSSION/SIGNIFICANCE OF FINDINGS: Breath collection devices can be used in intensive care units, outpatient clinics, workplaces, and at home. EBC analysis has been used to monitor asthma and chronic obstructive pulmonary disease. It can be applied to infectious respiratory diseases (e.g. influenza, COVID-19) and for monitoring environmental and occupational chemical exposures.
In December 2016, Public Health England investigated an outbreak of campylobacteriosis in North West England, with 69 cases in total. Epidemiological, microbiological and environmental investigations associated the illness with the consumption of unpasteurised cows' milk from Farm X, where milk was predominantly sold from a vending machine. Campylobacter was detected in milk samples which, when sequenced, were identical in sequence type as pathogens isolated from cases (Clonal Complex ST-403, Sequence Type 7432). The farm was served with a Hygiene Emergency Prohibition Order to prevent further cases. To our knowledge, this is the first outbreak of campylobacter associated with unpasteurised milk in England since 1996. Our findings highlighted several important lessons, including that the current testing regime in England for unpasteurised milk is not fit for purpose and that the required warning label should include additional wording, underscoring the risk to vulnerable groups. There has been a substantial increase in both the volume of unpasteurised milk consumed in England and the use of vending machines to sell unpasteurised milk over the last 10 years, making unpasteurised milk more readily accessible to a wider population. The evidence generated from outbreaks like this is therefore critical and should be used to influence policy development.
Solvency II came into force on 1 January 2016 and included a transitional measure on technical provisions (“TMTP”) designed to help smooth in the capital impact of Solvency II over a 16-year period. The working party’s view is that the main intention of the TMTP is to mitigate the impact of the introduction of the risk margin, which significantly increases the technical provisions of firms, relative to their Solvency I Pillar 2 liabilities.
The majority of firms who hold a TMTP have now had at least one recalculation approved by the Prudential Regulation Authority (PRA); or are in the process of applying for a recalculation. Despite this large number of approved recalculations, there remains significant uncertainty in the industry around the approach and triggers for recalculation.
This paper considers aspects of TMTP recalculation for regulated UK life firms, for example practicalities of the calculation, asset and liability considerations, and communications/announcements.
In this paper, we outline the need for pragmatism when considering the approach to recalculation of a measure originally intended to serve as the bridge between two regimes. We call for an allowance for doing what is sensible in a principles-based regime balancing what might be more theoretically correct with what is practical and possible to support effective management of the business.
Prior studies have demonstrated that both bacterial vaginosis (BV) and sexually transmitted infections (STIs) are strong independent risk factors for subsequent STI. In observational studies of this biological enhancement (BE) hypothesis, it is important to adjust for the risk of STI exposure so that the independent effect of BE can be assessed. We sought to model if two markers of local sexual network (partner concurrency and cumulative number of STIs) represented residual confounding in the models of risk for subsequent infection in a study that screened 3620 women for STIs every 3 months for a year. Mixed-effects logistic regression was used to calculate the odds ratios for an incident diagnosis of Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis and BV following a diagnosis of any of these four at the prior visit, controlling for the cumulative number of STIs and partner concurrency variables. We found that partner concurrency and cumulative number of STIs were each associated with incident infection, and in general, controlling for these variables reduced the strength of the association between prior and incident infections. We conclude that the frequently found association between prior and incident STIs is associated with both BE and sexual network structure.
There is considerable uncertainty as to the effectiveness of Neisseria gonorrhoeae (NG) screening in men who have sex with men. It is important to ensure that screening has benefits that outweigh the risks of increased antibiotics resistance. We develop a mathematical model to estimate the effectiveness of screening on prevalence. Separable Temporal Exponential family Random Graph Models are used to model the sexual relationships network, both with main and casual partners. Next, the transmission of Gonorrhoea is simulated on this network. The models are implemented using the R package ‘statnet’, which we adapted among other things to incorporate infection status at the pharynx, urethra and rectum separately and to distinguish between anal sex, oral sex and rimming. The different screening programmes compared are no screening, 3.5% of the population screened, 32% screened and 50% screened. The model simulates day-by-day evolution for 10 years of a population of 10 000. If half of the population would be screened, the prevalence in the pharynx decreases from 11.9% to 10.2%. We conclude that the limited impact of screening on NG prevalence may not outweigh the increased risk of antibiotic resistance.
The foetal mammary gland is sensitive to maternal weight and nutrition during gestation, which could affect offspring milk production. It has previously been shown that ewes born to dams offered maintenance nutrition during pregnancy (day 21 to 140 of gestation) produced greater milk, lactose and CP yields in their first lactation when compared with ewes born to dams offered ad libitum nutrition. In addition, ewes born to heavier dams produced greater milk and lactose yields when compared with ewes born to lighter dams. The objective of this study was to analyse and compare the 5-year lactation performance of the previously mentioned ewes, born to heavy or light dams that were offered maintenance or ad libitum pregnancy nutrition. Ewes were milked once per week, for the first 6 weeks of their lactation, for 5 years. Using milk yield and composition data, accumulated yields were calculated over a 42-day period for each year for milk, milk fat, CP, true protein, casein and lactose using a Legendre orthogonal polynomial model. Over the 5-year period, ewes born to heavy dams produced greater average milk (P=0.04), lactose (P=0.01) and CP (P=0.04) yields than offspring born to light dams. In contrast, over the 5-year period dam nutrition during pregnancy did not affect average (P>0.05) offspring milk yields or composition, but did increase milk and lactose accumulated yield (P=0.03 and 0.01, respectively) in the first lactation. These results indicate that maternal gestational nutrition appears to only affect the first lactational performance of ewe offspring. Neither dam nutrition nor size affected grand-offspring live weight gain to, or live weight at weaning (P>0.05). Combined these data indicate that under the conditions of the present study, manipulating dam weight or nutrition in pregnancy can have some effects of offspring lactational performance, however, these effects are not large enough to alter grand-offspring growth to weaning. Therefore, such manipulations are not a viable management tool for farmers to influence lamb growth to weaning.
We assessed if there has been a decline in the median number of reported lifetime sexual partners in Kenya following the AIDS epidemic. The Wilcoxon rank-sum test was used to compare the median and interquartile range (IQR) of the number of lifetime sexual partners for men aged 20–54 years in the 1993 and 2008 Kenyan Demographic Health Surveys. The median number of sexual partners in 1993 increased rapidly to 10 partners reported at age 30 years then plateaued at this level. In 2008, the median number of sexual partners plateaued at around half the value of the 1993 plateau. The median number of lifetime sexual partners for men aged 20–54 years declined from 10 (IQR 4-20) in 1993 to 3 (IQR 2-7) in 2008 (P < 0·001). This decline could be due to a combination of the effects of AIDS mortality and a misreporting bias.
We report a study of resistive switching in a silicon-based memristor/resistive RAM (RRAM) device in which the active layer is silicon-rich silica. The resistive switching phenomenon is an intrinsic property of the silicon-rich oxide layer and does not depend on the diffusion of metallic ions to form conductive paths. Both unipolar and bipolar programming is demonstrated.
Switching exhibits the pinched hysteresis I/V loop characteristic of RRAM/memristive systems, and on/off resistance ratios of 104:1 or higher can be easily achieved. Scanning Tunnelling Microscopy suggests that switchable conductive pathways are 10nm in diameter or smaller.
Mid-pregnancy shearing has consistently been shown to increase lamb birth weight, which can lead to an increase in lamb survival rates. However, shearing ewes during the winter months and under outdoor pastoral farming conditions can expose the recently shorn ewe to a greater risk of hypothermia. The aim of this study was to determine if exposure of ewes to repeated stressors, in mid- and late pregnancy, would result in an increase in lamb birth weight. This information may assist in the elucidation of the mechanism for the birth weight response to mid-pregnancy shearing, which in turn could assist in the design of management options to increase lamb birth weight without placing the ewe at risk. One hundred and forty-four twin-bearing Romney ewes were allocated to one of six mid-pregnancy treatments: control, isolation on 2 or 10 occasions, sham-shearing on 10 occasions, intramuscular cortisol injection on 10 occasions or shearing. Isolation, sham-shearing and cortisol treatments were conducted twice a week beginning, on average, day 74 of pregnancy and shearing occurred on day 76. During pregnancy, ewe treatment had no effect on ewe live weight. However, average ewe body condition scores were higher in the shorn group than in the sham-shorn or cortisol groups (P < 0.05). Intramuscular injections of cortisol had a greater effect on ewe plasma cortisol concentrations than all other treatments (P < 0.05). Shearing produced a greater plasma cortisol response than isolation × 10 and sham-shearing (P < 0.05). Ewe plasma cortisol responses decreased during the 5 weeks of isolation and sham-shearing but cortisol injections produced a greater response during the fifth treatment than the first or ninth treatments (P < 0.05). Lambs born to shorn ewes were heavier and had a longer crown rump, forelimb and hind limb lengths than all other lambs (P < 0.05). In addition, lambs born to ewes in the cortisol treatment were lighter than lambs born to control, isolation × 2, isolation × 10 and shorn ewes (P < 0.05). The plasma cortisol concentrations observed for ewes injected with cortisol were far greater than those observed in all other groups, which is likely to explain the low birth weights of lambs born to ewes in that group. These results indicate that the mechanism by which mid-pregnancy shearing increases lamb birth weight is unlikely to be repeated stressors.
The present study investigated the effects of maternal plasma iodine concentration on twin- and triplet-born lamb plasma thyroid hormone concentrations, rectal temperature and maximal heat production. On pregnancy day 68 (P68), 16 twin- and 14 triplet-bearing ewes were randomly chosen from ewes that were injected intramuscularly with 1·5 ml of iodized peanut oil and ewes that were not. Selected ewes were grazed on ad libitum pasture from P68 until parturition. After parturition, lamb blood samples were collected within 5 min of birth and at 3, 12 and 24–36 h after birth. Lamb rectal temperatures were measured within 5 min of birth and at 1, 3 and 12 h after birth. Lamb body weight, crown–rump length and thoracic-girth circumference were recorded at 3 h of age, and the capability of the lamb to produce heat at 24–36 h of age was measured using indirect open-circuit calorimetry. Maternal iodine supplementation successfully increased plasma iodine concentrations of twin- and triplet-bearing ewes throughout pregnancy, but had no effect on the rectal temperature, thyroid hormone concentration and maximal heat production of twin- or triplet-born lambs. Compared with twin-born lambs, triplet-born lambs had lower birth weights, rectal temperatures and plasma T4 and T3 concentrations within 5 min of birth. Overall, under the conditions of the present study, maternal iodine supplementation offered no benefit in improving lamb heat production.
In the UK, recent mean temperatures have consistently increased by between 1°C and 4°C compared to the 30-year monthly averages. Furthermore, all available predictive models for the UK indicate that the climate is likely to change further and feature more extreme weather events and a trend towards wetter, milder winters and hotter, drier summers. These changes will alter the prevalence of endemic diseases spatially and/or temporally and impact on animal health and welfare. Most notable among these endemic parasites are the helminths, which have been shown to be very strongly influenced by both the short-term weather and climate through effects on their free-living larval stages on pasture. In this review, we examine recent trends in prevalence and epidemiology of key helminth species and consider whether these could be climate-related. We identify likely effects of temperature and rainfall on the free-living stages and some key parasite traits likely to determine parasite abundance under changed climatic conditions. We find clear evidence that climate change, especially elevated temperature, has already changed the overall abundance, seasonality and spatial spread of endemic helminths in the UK. We explore some confounders and alternative explanations for the observed patterns. Finally, we explore the implications of these findings for policy makers and the livestock industry and make some recommendations for future research priorities.
This experiment was conducted to evaluate the effect of offering ewes two different feeding levels, during mid and late pregnancy, on ewe and lamb behaviour 12 to 24 h after birth. Romney ewes, bearing twin (n = 80) or triplet foetuses (n = 56), were allocated to a pasture sward height of 2 or 4 cm between 70 and 107 days of pregnancy. In late pregnancy (day 107 to 147), half of the ewes were reallocated the alternate sward height, which produced four treatments: 2-2, 2-4, 4-2 and 4-4. Ewes were weighed on days 65, 92, 107 and 130 of pregnancy and lamb live weights were recorded 12 to 24 h after birth. Twelve to 24 h after birth the maternal behaviour score (MBS) of the ewes were determined, whilst their lambs were tagged. After the lambs were released, the behaviour of each ewe and her lambs was observed for 5 min. Ewe treatment and litter size had no effect on ewe MBS. However, as MBS increased (ewes stayed closer to lambs during tagging), ewes bleated less in a high-pitch and were quicker to make contact with their lamb. During the observation period, ewes in the 4-4 treatment had a greater percentage of their bleats in a low pitch (P < 0.05) than ewes in the 2-2 and 4-2 treatment (61.3% v. 41.3% and 38.8% low bleats, respectively) and more lambs born to 4-4 ewes (95%) bleated than lambs born to 2-2 ewes (84%; P < 0.05). However, lambs born to ewes in the 2-2 treatment bleated earlier than lambs in all other treatments (P < 0.05). Lambs born to 4-4 ewes were less likely (P < 0.05) to move towards their dam in order to make contact than lambs born to 2-2 or 4-2 ewes (3.1% v. 16.9% and 16.7%, respectively). These findings suggest that under the conditions of the present study, ewe nutrition had little effect on maternal behaviour. However, lambs born to ewes offered 2 cm pasture sward heights during mid and/or late pregnancy (2-2, 2-4 and 4-2 treatments) displayed behaviour that demonstrated greater ‘need’ whereas lambs born to ewes offered 4 cm during mid and late pregnancy sought less attention from their dam.
The current study investigated the effect of offering concentrate supplement to ewes in late pregnancy on twin- and triplet-born lamb heat production at 24–36 h old and performance from birth until lactation day 94 (L94). Twin- (n=40) and triplet-bearing (n=28) ewes were grazed on a 60 mm sward height from day 70 of pregnancy (P70) until L94. From P100, half of the ewes from each litter size were offered 400 g/ewe/day of concentrate sheep pellets. Ewe liveweight and body condition were recorded on P50, 100, 130, 135 and 140. Ewe blood samples were also collected on P130, 135 and 140, and ewe herbage intake was estimated from P133–136 using the n-alkane method. Lamb measurements included liveweight and body size at birth, production of heat using indirect open-circuit calorimetry at 24–36 h old and liveweight at L94. Blood samples were also collected from lambs at 24–36 h old and directly before and after calorimetry measurements. While estimates of ewe herbage intake suggested that substitution of herbage for concentrate did not occur, offering concentrate supplement failed to improve ewe liveweight gain, or birth weight of lambs. Offering concentrate supplement, however, did have a positive effect (P<0·05) on the maximal amount of heat a triplet-born lamb can produce on a per kg of body weight basis (concentrate 21±1·3 W/kg, non-concentrate 17±0·6 W/kg). It also had a positive effect (P<0·05) on lamb square-root-transformed plasma gamma-glutamyl transferase (GGT) concentrations, an indicator of colostrum uptake (concentrate 46±3·1 U/l, non-concentrate 38±2·9 U/l). Irrespective of lamb birth rank, offering concentrate supplement had a positive effect (P<0·01) on liveweight gain per day from birth until L94 (concentrate 261±5·7 g/day, non-concentrate 239±5·8 g/day), although there was no effect on the total weight of lamb reared/ewe. Supplementation with concentrate resulted in triplet-born lambs that produced more heat which may have positive effects on the ability of the newborn lamb to deal with cold stress and potentially its survival. Offering concentrate supplement also produced greater lamb growth in twin- and triplet-born lambs.
The Gattini-DomeC project, part of the IRAIT site testing campaign and ongoing since January 2006, consists of two cameras for the measurement of optical sky brightness, large area cloud cover, and auroral detection above the DomeC site, home of the French-Italian Concordia station. The cameras are transit in nature and are virtually identical except for the nature of the lenses. The cameras have operated throughout the past two Antarctic winter seasons and here we present the results obtained from the 2006 winter-time dataset of the wide field “All-sky camera".
The Gattini cameras are two site testing instruments for the measurement of optical sky brightness, large area cloud cover and auroral detection of the night sky above the high altitude Dome C site in Antarctica. The cameras have been operating since installation in January 2006 and are currently at the end of the first Antarctic winter season. The cameras are transit in nature and are virtually identical, both adopting Apogee Alta CCD detectors. By taking frequent images of the night sky we obtain long term cloud cover statistics, measure the sky background intensity as a function of solar and lunar altitude and phase and directly measure the spatial extent of bright aurora if present and when they occur. The full data set will return in December 2006 however a limited amount of data has been transferred via the Iridium network enabling preliminary data reduction and system evaluation. An update of the project is presented together with preliminary results from data taken since commencement of the winter season.
A key to long-term sustainable enhancement of viable livestock production is the introduction of genetic traits that ensure that fertility and meat quality characteristics are compatible with farming environments and market needs. For example, the sheep industry could benefit if daughters of hill-breed ewes were of a crossbred genotype that enhances both carcass characteristics and fertility traits. Use of sires that confer better conformation is an option but does not significantly boost prolificacy. Introduction of the ‘Inverdale’ fecundity gene could change this. On a flock basis in the Romney breed, mean ovulation is increased by 1.0 and litter size by 0.6 in adult ewes carrying a single copy of this gene (designated as FecXI because it is on the X chromosome; Davis et al. 1992). Carrier males transmit it to all of their female offspring, these being heterozygous carriers of the gene unless it also is maternally inherited. In the latter instance, young would be infertile the homozygous genotype confers an undesirable ‘streak ovary’ phenotype. Although a number of sheep breeds world-wide exhibit significant ‘single gene’ effects on ovulation and litter size (Montgomery et al. 2001), Scottish hill sheep breeds show no evidence of this. Consequently, all ewe lambs generated by crossing these hill ewes with a ram carrying the Inverdale gene should be heterozygous. To ascertain whether such animals exhibit enhanced fecundity, an on-farm study investigated ovulation incidence in cyclic ewe lambs born to Cheviot or Scottish Blackface ewes that had been bred to Texel rams carrying a single copy of the ‘Inverdale’ gene.
High-frequency oscillatory potentials (HFOPs) have been recorded from
ganglion cells in cat, rabbit, frog, and mudpuppy retina and in
electroretinograms (ERGs) from humans and other primates. However, the
origin of HFOPs is unknown. Based on patterns of tracer coupling, we
hypothesized that HFOPs could be generated, in part, by negative
feedback from axon-bearing amacrine cells excited via
electrical synapses with neighboring ganglion cells. Computer
simulations were used to determine whether such axon-mediated feedback
was consistent with the experimentally observed properties of HFOPs.
(1) Periodic signals are typically absent from ganglion cell PSTHs, in
part because the phases of retinal HFOPs vary randomly over time and
are only weakly stimulus locked. In the retinal model, this phase
variability resulted from the nonlinear properties of axon-mediated
feedback in combination with synaptic noise. (2) HFOPs increase as a
function of stimulus size up to several times the receptive-field
center diameter. In the model, axon-mediated feedback pooled signals
over a large retinal area, producing HFOPs that were similarly size
dependent. (3) HFOPs are stimulus specific. In the model, gap junctions
between neighboring neurons caused contiguous regions to become phase
locked, but did not synchronize separate regions. Model-generated HFOPs
were consistent with the receptive-field center dynamics and spatial
organization of cat alpha cells. HFOPs did not depend qualitatively on
the exact value of any model parameter or on the numerical precision of
the integration method. We conclude that HFOPs could be mediated, in
part, by circuitry consistent with known retinal anatomy.
Psoroptes ovis, the causative agent of sheep scab, is an important ectoparasitic mite infecting sheep, goats and cattle. Infection is characterized by an extensive dermatitis, scab formation and intense itching. Initial focal lesions spread outwards, coalesce and may extend over the whole body. The host response to infestation has all the characteristics of an immediate-type hypersensitivity reaction but the mite antigens and allergens which initiate this response are almost completely undefined. Here, 507 randomly selected cDNAs derived from a mixed population of P. ovis were sequenced and the resultant nucleotide sequences subjected to Cluster analysis and Blast searches. This analysis yielded 280 clusters of which 49 had >1 sequence with 24 showing significant Blast X homology to another protein in the databases. There were 231 sequences which appeared on one occasion and 109 of these showed significant Blast X homology to other sequences in the databases. This analysis identified homologues of 9 different types of allergens which have been characterized in other allergic conditions such as responses to house dust mites. It also identified a number of cysteine proteases which may contribute to lesion development as well as several free-radical scavenging enzymes which may protect the mite from host immune effector responses.
High throughput, thin film synthesis methods have been used to make libraries of diverse metallic and metal-chalcogenide compositions. These libraries have been subject to a variety of screening protocols, including X-ray diffraction (XRD) after repeated annealing steps, and the measurement of temperature dependent electrical properties. The application of these methods for the development of materials for non-magnetic storage media is presented.