Circulating Apolipoprotein E Concentration and Cardiovascular Disease Risk: Meta-analysis of Results from Three Studies

Background: The association of APOE genotype with circulating apolipoprotein E (ApoE) concentration and cardiovascular disease (CVD) risk is well established. However, the relationship of circulating ApoE concentration and CVD has received little attention. Methods and Findings: To address this, we measured circulating ApoE concentration in 9,587 individuals (with 1,413 CVD events) from three studies with incident CVD events: two population-based studies, the English Longitudinal Study of Ageing (ELSA) and the men-only Northwick Park Heart Study II (NPHSII), and a nested sub-study of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). We examined the association of circulating ApoE with cardiovascular risk factors in the two population-based studies (ELSA and NPHSII) and the relationship between ApoE concentration and coronary heart disease and stroke in all three studies. Analyses were carried out within study, and, where appropriate, pooled effect estimates were derived using meta-analysis. In the population-based samples, circulating ApoE was associated with systolic blood pressure (correlation coefficient 0.08, p < 0.001, in both ELSA and NPHSII), total cholesterol (correlation coefficient 0.46 and 0.34 in ELSA and NPHSII, respectively; both p < 0.001), low-density lipoprotein cholesterol (correlation coefficient 0.30 and 0.14, respectively; both p < 0.001), high-density lipoprotein (correlation coefficient 0.16 and ?0.14, respectively; both p < 0.001), and triglycerides (correlation coefficient 0.43 and 0.46, respectivly; both p < 0.001). In NPHSII, ApoE concentration was additionally associated with apolipoprotein B (correlation coefficient 0.13, p = 0.001) and lipoprotein(a) (correlation coefficient ?0.11, p < 0.001). In the pooled analysis of ASCOT, ELSA, and NPHSII, there was no association of ApoE with CVD events; the odds ratio (OR) for CVD events per 1-standard-deviation higher ApoE concentration was 1.02 (95% CI 0.96, 1.09). After adjustment for cardiovascular risk factors, the OR for CVD per 1-standard-deviation higher ApoE concentration was 0.97 (95% CI 0.82, 1.15). Limitations of these analyses include a polyclonal method of ApoE measurement, rather than isoform-specific measurement, a moderate sample size (although larger than any other study to our knowledge and with a long lag between ApoE measures), and CVD events that may attenuate an effect. Conclusions: In the largest study to date on this question, we found no evidence of an association of circulating ApoE concentration with CVD events. The established association of APOE genotype with CVD events may be explained by isoform-specific functions as well as other mechanisms, rather than circulating concentrations of ApoE

Groundwater residence time in the Kulnura-Mangrove Mountain Plateau (Gosford, NSW, Australia)

The Kulnura-Mangrove Mountain plateau consists of the catchments of Mangrove, Narara, Mooney Mooney, and Ourimbah Creeks, and Wyong River. Groundwater plays a key role in sustaining stream flow within these catchments. Estimates indicate up to 50% of annual stream flow is derived from baseflow. The local community water supply relies on the groundwater within the elevated Hawkesbury- Narrabeen sandstone plateau. Furthermore, the Gosford-Wyong Councils’ Water Authority (WSA) is the third largest in NSW and utilises many of the streams flowing from the sandstone plateau for municipal water supply. It is anticipated that the WSA will provide municipal water for 319 000 persons by the year 2010. The increasing volumes of groundwater being extracted and changing land use have the potential to cause damage to the fresh water aquifer through contamination and aquifer depletion. A hydrogeochemical survey (2006-2009) has been conducted in NSW Dept of Water and Energy (DWE) monitoring wells across the plateau in order to determine groundwater residence times. Groundwater was analysed for major ions, minor and trace elements, H2O 18O and 2H, 13CDIC, 87Sr/86Sr, 14CDIC, and 3H, and complemented with mineralogical and isotopic information obtained from soil and drill chips collected during well construction. Water stable isotopes confirm the meteoric origin of the groundwater with most values plotting on the local meteoric water line. Localised evaporative trends suggest recharge with evaporated groundwater stored in ponds. Shallow groundwaters have 3H and 14C activities consistent with modern recharge (Fig 1). Carbon “bomb pulse” signatures of up to 116.8 pmC are found in the central areas of the plateau. The thin soils, lack of carbonates in the intensely weathered near-surface Hawkesbury sandstone, and the shallow depth of the water samples is consistent with the 3H results measured, suggesting minimal dilution of the original 14C. Input of this data into a southern hemisphere bomb pulse model [1] suggest potential recharge during the 1990´s, coinciding with sustained wet conditions and above average rainfalls experienced during this period. Fig. 1. 14C vs 3H plot of groundwater samples in the Kulnura- Mangrove Mountain Plateau Deeper groundwaters have lower 14C and 3H activities in some cases close to background level (Fig. 1). The quantifiable 3H suggests residence times of <70 a. However, non-corrected 14C residence times are submodern (>500 a). This apparent discrepancy can be explained by either mixing with older waters or dissolution of carbonates. The good correlation of total dissolved inorganic carbon (TDIC) and Ca (R2=0.8), 13CTDIC in groundwater and mineralogy results from drill chips suggest that dissolution of dispersed carbonates is taking place. The deepest groundwaters show the most difference in residence time across the study area. The eastern and western plateaus yield old groundwater with 14C corrected residence times of around 9 ka and 4 ka respectively. However, the groundwater at equivalent depths in the central plateau was found to be considerably younger with residence times of <70 a

A comparison between direct and pan-derived measurements of the isotopic composition of atmospheric waters

The stable isotopes of water can be used to examine and quantify the contribution to atmospheric moisture from evaporation, transpiration and surface-waters. However, obtaining extensive and ongoing time series data of the isotopic composition of atmospheric moisture has been difficult. Presented here is an alternate method using an isotope mass balance approach to estimate the isotopic composition of atmospheric moisture using water samples collected from class A evaporation pans. While this evaporation pan method does not provide the high-resolution time series data that can be obtained from an isotope analyser taking in-situ measurements of atmospheric moisture, the method is relatively simple and inexpensive to set-up and maintain. In this preliminary investigation, a comparison between the isotopic composition of atmospheric moisture estimated from the evaporation pan method and in-situ measurements of the isotopic composition of water vapour using a Fourier Transform Infrared (FTIR) spectrometer deployed at the Lucas Heights weather station in New South Wales is undertaken. Through comparison of the two series of hydrogen isotope data, an assessment of the evaporation pan method can be made. Although there was some agreement between the isotopic composition of vapour measured by the FTIR spectrometer and the estimation for the atmospheric moisture (R2 = 0.49), the comparison is sensitive to climatic parameters that vary significantly within a 24-hour period such as the relative humidity of air and the air and pan temperatures. Inverting the model to use the FTIR spectrometer measurements at an hourly resolution improved the performance of the model (R2 =0.57). However, this also revealed that the model produced more depleted values of the evaporation pan water isotopes than those observed. In contrast, there was a variable relationship between the modelled and observed isotope values of atmospheric moisture. These conflicting results will need to be resolved before the evaporation pan method is broadly applied in isotope hydrology. © 2011 The Modelling and Simulation Society of Australia and New Zealand Inc

Selection at a single locus leads to widespread expansion of toxoplasma gondii lineages that are virulent in mice

The determinants of virulence are rarely defined for eukaryotic parasites such as T. gondii, a widespread parasite of mammals that also infects humans, sometimes with serious consequences. Recent laboratory studies have established that variation in a single secreted protein, a serine/threonine kinase known as ROPO18, controls whether or not mice survive infection. Here, we establish the extent and nature of variation in ROP18among a collection of parasite strains from geographically diverse regions. Compared to other genes, ROP18 showed extremely high levels of diversification and changes in expression level, which correlated with severity of infection in mice. Comparison with an out-group demonstrated that changes in the upstream region that regulates expression of ROP18 led to an historical increase in the expression and exposed the protein to diversifying selective pressure. Surprisingly, only three atypically distinct protein variants exist despite marked genetic divergence elsewhere in the genome. These three forms of ROP18 are likely adaptations for different niches in nature, and they confer markedly different virulence to mice. The widespread distribution of a single mouse-virulent allele among geographically and genetically disparate parasites may have consequences for transmission and disease in other hosts, including humans

Parental cultural models and resources for understanding mathematical achievement in culturally diverse school settings

This paper proposes that the theoretical concept of cultural models can offer useful insights into parental involvement in their child’s mathematical achievement and the resources they use to go about gaining information in culturally diverse learning settings. This examination takes place within a cultural-developmental framework and draws on the notion of cultural models to explicate parental understandings of their child’s mathematics achievement and what resources are used to make sense of this. Three parental resources are scrutinized: (a) the teacher, (b) examination test results, and (c) constructions of child development. The interviews with 22 parents revealed some ambiguity around the interpretation of these resources by the parent, which was often the result of incongruent cultural models held between the home and the school. The resources mentioned are often perceived as being unambiguous but show themselves instead to be highly interpretive because of the diversity of cultural models in existence in culturally diverse settings. Parents who are in minority or marginalized positions tend to have difficulties in interpreting cultural models held by school, thereby disempowering them to be parentally involved in the way the school would like

A preliminary study on the induction of dioestrous ovulation in the mare – a possible method for inducing prolonged luteal phase

BACKGROUND: Strong oestrous symptoms in the mare can cause problems with racing, training and handling. Since long-acting progesterone treatment is not permitted in mares at competition (e.g. according to FEI rules), there is a need for methods to suppress unwanted cyclicity. Spontaneous dioestrous ovulations in the late luteal phase may cause a prolongation of the luteal phase in mares. METHODS: In this preliminary study, in an attempt to induce ovulation during the luteal phase, human chorionic gonadotropin (hCG) (3000 IU) was injected intramuscularly in four mares (experimental group) in the luteal phase when a dioestrous follicle ≥ 30 mm was detected. A fifth mare included in this group was not treated due to no detectable dioestrous follicles ≥ 30 mm. Four control mares were similarly injected with saline. The mares were followed with ultrasound for 72 hours post injection or until ovulation. Blood samples for progesterone analysis were obtained twice weekly for one month and thereafter once weekly for another two to four months. RESULTS: Three of the hCG-treated mares ovulated within 72 hours after treatment and developed prolonged luteal phases of 58, 68 and 82 days respectively. One treated mare never ovulated after the hCG injection and progesterone levels fell below 3 nmol/l nine days post treatment. Progesterone levels in the control mares were below 3 nmol/l within nine days after saline injection, except for one mare, which developed a spontaneously prolonged luteal phase of 72 days. CONCLUSION: HCG treatment may be a method to induce prolonged luteal phases in the mare provided there is a dioestrous follicle ≥ 30 mm that ovulates post-treatment. However, the method needs to be tested on a larger number of mares to be able to draw conclusions regarding its effectiveness

Mass-producible 2D-WS2 bulk modified screen printed electrodes towards the hydrogen evolution reaction

© The Royal Society of Chemistry 2019. A screen-printable ink that contained varying percentage mass incorporations of two dimensional tungsten disulphide (2D-WS2) was produced and utilized to fabricate bespoke printed electrodes (2D-WS2-SPEs). These WS2-SPEs were then rigorously tested towards the Hydrogen Evolution Reaction (HER) within an acidic media. The mass incorporation of 2D-WS2 into the 2D-WS2-SPEs was found to critically affect the observed HER catalysis with the larger mass incorporations resulting in more beneficial catalysis. The optimal (largest possible mass of 2D-WS2 incorporation) was the 2D-WS2-SPE40%, which displayed a HER onset potential, Tafel slope value and Turn over Frequency (ToF) of -214 mV (vs. RHE), 51.1 mV dec-1 and 2.20, respectively. These values significantly exceeded the HER catalysis of a bare/unmodified SPE, which had a HER onset and Tafel slope value of -459 mV (vs. RHE) and 118 mV dec-1, respectively. Clearly, indicating a strong electrocatalytic response from the 2D-WS2-SPEs. An investigation of the signal stability of the 2D-WS2-SPEs was conducted by performing 1000 repeat cyclic voltammograms (CVs) using a 2D-WS2-SPE10% as a representative example. The 2D-WS2-SPE10% displayed remarkable stability with no variance in the HER onset potential of ca. -268 mV (vs. RHE) and a 44.4% increase in the achievable current over the duration of the 1000 CVs. The technique utilized to fabricate these 2D-WS2-SPEs can be implemented for a plethora of different materials in order to produce large numbers of uniform and highly reproducible electrodes with bespoke electrochemical signal outputs