Syncytiotrophoblast extracellular vesicles from pre-eclampsia placentas differentially affect platelet function

Pre-eclampsia (PE) complicates around 3% of all pregnancies and is one of the most common causes of maternal mortality worldwide. The pathophysiology of PE remains unclear however its underlying cause originates from the placenta and manifests as raised blood pressure, proteinuria, vascular or systemic inflammation and hypercoagulation in the mother. Women who develop PE are also at significantly higher risk of subsequently developing cardiovascular (CV) disease. In PE, the failing endoplasmic reticulum, oxidative and inflammatory stressed syncytiotrophoblast layer of the placenta sheds increased numbers of syncytiotrophoblast extracellular vesicles (STBEV) into the maternal circulation. Platelet reactivity, size and concentration are also known to be altered in some women who develop PE, although the underlying reasons for this have not been determined. In this study we show that STBEV from disease free placenta isolated ex vivo by dual placental perfusion associate rapidly with platelets. We provide evidence that STBEV isolated from normal placentas cause platelet activation and that this is increased with STBEV from PE pregnancies. Furthermore, treatment of platelets with aspirin, currently prescribed for women at high risk of PE to reduce platelet aggregation, also inhibits STBEV-induced reversible aggregation of washed platelets. Increased platelet reactivity as a result of exposure to PE placenta derived STBEVs correlates with increased thrombotic risk associated with PE. These observations establish a possible direct link between the clotting disturbances of PE and dysfunction of the placenta, as well as the known increased risk of thromboembolism associated with this condition.

Climate change and heat-related mortality in six cities Part 2: climate model evaluation and projected impacts from changes in the mean and variability of temperature with climate change

Previous assessments of the impacts of climate change on heat-related mortality use the "delta method" to create temperature projection time series that are applied to temperature-mortality models to estimate future mortality impacts. The delta method means that climate model bias in the modelled present does not influence the temperature projection time series and impacts. However, the delta method assumes that climate change will result only in a change in the mean temperature but there is evidence that there will also be changes in the variability of temperature with climate change. The aim of this paper is to demonstrate the importance of considering changes in temperature variability with climate change in impacts assessments of future heat-related mortality. We investigate future heatrelated mortality impacts in six cities (Boston, Budapest, Dallas, Lisbon, London and Sydney) by applying temperature projections from the UK Meteorological Office HadCM3 climate model to the temperature-mortality models constructed and validated in Part 1. We investigate the impacts for four cases based on various combinations of mean and variability changes in temperature with climate change. The results demonstrate that higher mortality is attributed to increases in the mean and variability of temperature with climate change rather than with the change in mean temperature alone. This has implications for interpreting existing impacts estimates that have used the delta method. We present a novel method for the creation of temperature projection time series that includes changes in the mean and variability of temperature with climate change and is not influenced by climate model bias in the modelled present. The method should be useful for future impacts assessments. Few studies consider the implications that the limitations of the climate model may have on the heatrelated mortality impacts. Here, we demonstrate the importance of considering this by conducting an evaluation of the daily and extreme temperatures from HadCM3, which demonstrates that the estimates of future heat-related mortality for Dallas and Lisbon may be overestimated due to positive climate model bias. Likewise, estimates for Boston and London may be underestimated due to negative climate model bias. Finally, we briefly consider uncertainties in the impacts associated with greenhouse gas emissions and acclimatisation. The uncertainties in the mortality impacts due to different emissions scenarios of greenhouse gases in the future varied considerably by location. Allowing for acclimatisation to an extra 2°C in mean temperatures reduced future heat-related mortality by approximately half that of no acclimatisation in each city.

Projected impacts on heat-related mortality from changes in the mean and variability of temperature with climate change

The aim of this paper is to demonstrate the importance of changing temperature variability with climate change in assessments of future heat-related mortality. Previous studies have only considered changes in the mean temperature. Here we present estimates of heat-related mortality resulting from climate change for six cities: Boston, Budapest, Dallas, Lisbon, London and Sydney. They are based on climate change scenarios for the 2080s (2070-2099) and the temperature-mortality (t-m) models constructed and validated in Gosling et al. (2007). We propose a novel methodology for assessing the impacts of climate change on heat-related mortality that considers both changes in the mean and variability of the temperature distribution.

Brief and precarious lives: Infant mortality in contrasting sites from medieval and post-medieval England (AD 850-1859)

This study compares the infant mortality profiles of 128 infants from two urban and two rural cemetery sites in medieval England. The aim of this paper is to assess the impact of urbanization and industrialization in terms of endogenous or exogenous causes of death. In order to undertake this analysis, two different methods of estimating gestational age from long bone lengths were used: a traditional regression method and a Bayesian method. The regression method tended to produce more marked peaks at 38 weeks, while the Bayesian method produced a broader range of ages and were more comparable with the expected "natural" mortality profiles. At all the sites, neonatal mortality (28-40 weeks) outweighed post-neonatal mortality (41-48 weeks) with rural Raunds Furnells in Northamptonshire, showing the highest number of neonatal deaths and post-medieval Spitalfields, London, showing a greater proportion of deaths due to exogenous or environmental factors. Of the four sites under study, Wharram Percy in Yorkshire showed the most convincing "natural" infant mortality profile, suggesting the inclusion of all births (i.e., stillbirths and unbaptised infants).

Maternal label and gesture use affects acquisition of specific object names

Ten mothers were observed prospectively, interacting with their infants aged 0 ; 10 in two contexts (picture description and noun description). Maternal communicative behaviours were coded for volubility, gestural production and labelling style. Verbal labelling events were categorized into three exclusive categories: label only; label plus deictic gesture; label plus iconic gesture. We evaluated the predictive relations between maternal communicative style and children's subsequent acquisition of ten target nouns. Strong relations were observed between maternal communicative style and children's acquisition of the target nouns. Further, even controlling for maternal volubility and maternal labelling, maternal use of iconic gestures predicted the timing of acquisition of nouns in comprehension. These results support the proposition that maternal gestural input facilitates linguistic development, and suggest that such facilitation may be a function of gesture type.

Climate change and heat-related mortality in six cities Part 1: model construction and validation

Heat waves are expected to increase in frequency and magnitude with climate change. The first part of a study to produce projections of the effect of future climate change on heat-related mortality is presented. Separate city-specific empirical statistical models that quantify significant relationships between summer daily maximum temperature (T max) and daily heat-related deaths are constructed from historical data for six cities: Boston, Budapest, Dallas, Lisbon, London, and Sydney. ‘Threshold temperatures’ above which heat-related deaths begin to occur are identified. The results demonstrate significantly lower thresholds in ‘cooler’ cities exhibiting lower mean summer temperatures than in ‘warmer’ cities exhibiting higher mean summer temperatures. Analysis of individual ‘heat waves’ illustrates that a greater proportion of mortality is due to mortality displacement in cities with less sensitive temperature–mortality relationships than in those with more sensitive relationships, and that mortality displacement is no longer a feature more than 12 days after the end of the heat wave. Validation techniques through residual and correlation analyses of modelled and observed values and comparisons with other studies indicate that the observed temperature–mortality relationships are represented well by each of the models. The models can therefore be used with confidence to examine future heat-related deaths under various climate change scenarios for the respective cities (presented in Part 2).

Associations between elevated atmospheric temperature and human mortality: a critical review of the literature

The effects of the anomalously warm European summer of 2003 highlighted the importance of understanding the relationship between elevated atmospheric temperature and human mortality. This review is an extension of the brief evidence examining this relationship provided in the IPCC’s Assessment Reports. A comprehensive and critical review of the literature is presented, which highlights avenues for further research, and the respective merits and limitations of the methods used to analyse the relationships. In contrast to previous reviews that concentrate on the epidemiological evidence, this review acknowledges the inter-disciplinary nature of the topic and examines the evidence presented in epidemiological, environmental health, and climatological journals. As such, present temperature–mortality relationships are reviewed, followed by a discussion of how these are likely to change under climate change scenarios. The importance of uncertainty, and methods to include it in future work, are also considered.

Effect of dietary supplementation of different oils during the first or second half of pregnancy on the glucose tolerance of the sow

Poor glucose tolerance may be an under-researched contributory factor in the high (10% to 20%) pre-weaning mortality rate observed in pigs. Insulin resistance commences at around week 12 of gestation in the sow, although there are conflicting reports in the literature about the extent to which insulin resistance is modulated by maternal diet. The aim of the study was to determine the effects of supplementing the maternal diet with different dietary oils during either the first half or the second half of gestation on the glucose tolerance of the sow. Sows were offered the control (C: n = 5) diet as pellets or the C diet plus 10% extra energy (h = 16 per group) derived from either. (i) extra pellets; (ii) palm oil; (iii) olive oil; (iv) sunflower oil; or (v) fish oil. Experimental diets were fed during either the first (G1) or second (G2) half of gestation. A glucose tolerance test (GTT) was conducted on day 108 of gestation by administering 0.5g/kg glucose i.v. Blood samples were taken every 5 to 10 min for 90 min post administration. The change in body weight and backfat thickness during gestation was similar but both type and timing of dietary supplementation influenced litter size and weight. With the exception of the sunflower oil group, supplementing the maternal diet in G1 resulted in larger and heavier litters, particularly in mothers offered palm oil. Basal blood glucose concentrations tended to be more elevated in G1 than G2 groups, whilst plasma insulin concentrations were similar Following a GTT, the adjusted area under the curve was greater in G1 compared to G2 sows, despite no differences in glucose clearance. Maternal diet appeared to influence the relationship between glucose curve characteristics following a GTT and litter outcome. In conclusion, the degree of insulin sensitivity can be altered by both the period during which maternal nutritional supplementation is offered and the fatty acid profile of the diet.

A maternal influence on the conditioning to plant cues of Aphidius colemani Viereck, parasitizing the aphid Myzus persicae Sulzer

The offspring of parasitoids, Aphidius colemani Viereck, reared on Brussels sprouts and emerging from Myzus persicae Sulzer on a fully defined artificial diet, show no preferences in a four-way olfactometer, either for the odour of the diet, the odour of Brussels sprouts, or the odour of two other crucifers (cabbage and Chinese cabbage). A similar lack of odour preferences is shown when the host aphids are exposed for parasitization (for 48 h) on cabbage, Chinese cabbage or wheat. However, if parasitization occurs on Brussels sprouts, a weak but statistically highly significant response to Brussels sprout odour is observed. Although as many as 30-35% of the parasitoids show no response to any odour, another 35% respond positively to the odour of Brussels sprout compared with responses to the odours of cabbage, Chinese cabbage or wheat of only approximately 10%. An analagous result is obtained when the parent parasitoids are reared on cabbage. In this case, significant positive responses of their offspring to cabbage odour occur only if the 48-h parasitization has occurred also on cabbage. However, with parasitoids from Brussels sprouts parasitizing the aphids for 48 h also on Brussels sprouts, the offspring subsequently emerging from pupae excised from the mummies show no preference for Brussels sprout odour. Thus, although the Brussels sprout cue had been experienced early in the development of the parasitoids, they only become conditioned to it when emerging from the mummy. Both male and female parasitoids respond very similarly in all experiments. It is proposed that the chemical cue (probably glucosinolates in these experiments) is most likely in the silk surrounding the parasitoid pupa, and that the mother may leave the chemical in or around the egg at oviposition, inducing chemical defences in her offspring to the secondary plant compounds that the offspring are likely to encounter.

Influence of porcine genotype on the abundance of thyroid hormones and leptin in sow milk and its impact on growth, metabolism and expression of key adipose tissue genes in offspring

Neonatal mortality is greater in commercial porcine genotypes, compared with the ancient Meishan breed that rapidly lay down adipose tissue; this may be related to hormones, such as triiodothyronine (T3) or leptin. Leptin is present in maternal milk; however, the extent to which this supply provides the neonate with leptin is unknown, but may play a role in growth and development. We investigated whether thyroid hormones and leptin concentrations in maternal milk differed between genotypes; and whether this influenced piglet concentrations or expression of genes involved in adipose tissue regulation. Eight Meishan and six commercial sows were entered into the study and milk samples from the day of parturition to day 4 postpartum was taken daily. The median birth weight piglet in each litter had a daily venous blood sample taken and was euthanised on day 4. Gene expressions of IGF-I, IGF-binding protein 3 (IGFBP-3), peroxisome proliferators activated receptor (PPAR) and glucocorticoid receptor (GR) were measured in adipose tissue using real-time PCR. T3 was increased in Meishan milk, but not in piglet plasma. Milk thyroxine was similar between breeds but commercial piglet levels were significantly higher. Leptin was higher in commercial sow milk throughout the study. Milk leptin was strongly correlated to plasma leptin during the first postnatal days and also to organ and body weight in Meishan piglets that also had significantly higher expression of GR, but not IGF-I, IGFBP-3 or PPAR. In conclusion, we have found a significant disparity in the provision of thyroid hormones in Meishan and commercial sow’s milk. These changes are not always translated to plasma concentrations of hormone in the piglet. Leptin appears to have a stronger role in growth and development in the Meishan genotype compared with commercial; along with the increased GR expression, this may also represent a potential mechanism behind the rapid accumulation of adipose tissue in Meishan piglets.

A longitudinal study of sero-conversion to tick-borne pathogens in smallholder dairy youngstock in Tanzania

A longitudinal study of sero-conversion of youngstock to the tick-borne pathogens Theileria parva, T mutans, Anaplasma marginale, Babesia bigemina and B. bovis was conducted over two years on smallholder dairy farms in Tanga region, Tanzania. There was evidence of maternal antibodies to all tick-borne pathogens in animals less than 18 weeks of age. Seroprevalence increased as expected with age in animals older than this but seroprevalence profiles underestimated the force of infection due to waning antibody levels between samplings. By the end of the 2-year study, less than 50% of study animals had seroconverted to each of the tick-borne pathogens investigated, consistent with the low levels of tick attachment observed on the study animals. Some associations between seroconversion to tick-borne pathogens, and counts of their known tick vectors on the animals, were identified as expected. However, some were not, suggesting that counts of some tick species may act as an index of rates of attachment of other vector species. Variation in acaricide treatment frequencies was not associated with variations in tick-borne pathogen seroprevalence suggesting that acaricides may be used more frequently than necessary on many farms. Most animals were zero-grazed, a management system associated with a significantly lower likelihood that animals seroconverted to any tick-borne pathogen exceptA. marginale. Seroprevalence varied locally with farm location (particularly for Babesia spp.) but was not well predicted by indices of ecological conditions. Our findings suggest that attempts to achieve a state of 'endemic stability' for tick-bome pathogens may be unreasonable on the smallholder dairy farms studied but reductions in the frequency of use of acaricides may be possible following prospective studies of effects on mortality and morbidity due to tick-bome pathogens. (c) 2005 Elsevier B.V. All rights reserved.