Tracking of plasma lipids and lipoproteins, within-person and year-to-year variability in plasma cholesterol levels among participants from age 8 to 18 in Project HeartBeat!

Coronary heart disease remains the leading cause of death in the United States and increased blood cholesterol level has been found to be a major risk factor with roots in childhood. Tracking of cholesterol, i.e., the tendency to maintain a particular cholesterol level relative to the rest of the population, and variability in blood lipid levels with increase in age have implications for cholesterol screening and assessment of lipid levels in children for possible prevention of further rise to prevent adulthood heart disease. In this study the pattern of change in plasma lipids, over time, and their tracking were investigated. Also, within-person variance and retest reliability defined as the square root of within-person variance for plasma total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides and their relation to age, sex and body mass index among participants from age 8 to 18 years were investigated. ^ In Project HeartBeat!, 678 healthy children aged 8, 11 and 14 years at baseline were enrolled and examined at 4-monthly intervals for up to 4 years. We examined the relationship between repeated observations by Pearson's correlations. Age- and sex-specific quintiles were calculated and the probability of participants to remain in the uppermost quintile of their respective distribution was evaluated with life table methods. Plasma total cholesterol, HDL-C and LDL-C at baseline were strongly and significantly correlated with measurements at subsequent visits across the sex and age groups. Plasma triglyceride at baseline was also significantly correlated with subsequent measurements but less strongly than was the case for other plasma lipids. The probability to remain in the upper quintile was also high (60 to 70%) for plasma total cholesterol, HDL-C and LDL-C. ^ We used a mixed longitudinal, or synthetic cohort design with continuous observations from age 8 to 18 years to estimate within person variance of plasma total cholesterol, HDL-C, LDL-C and triglycerides. A total of 5809 measurements were available for both cholesterol and triglycerides. A multilevel linear model was used. Within-person variance among repeated measures over up to four years of follow-up was estimated for total cholesterol, HDL-C, LDL-C and triglycerides separately. The relationship of within-person and inter-individual variance with age, sex, and body mass index was evaluated. Likelihood ratio tests were conducted by calculating the deviation of −2log (likelihood) within the basic model and alternative models. The square root of within-person variance provided the retest reliability (within person standard deviation) for plasma total cholesterol, HDL-C, LDL-C and triglycerides. We found 13.6 percent retest reliability for plasma cholesterol, 6.1 percent for HDL-cholesterol, 11.9 percent for LDL-cholesterol and 32.4 percent for triglycerides. Retest reliability of plasma lipids was significantly related with age and body mass index. It increased with increase in body mass index and age. These findings have implications for screening guidelines, as participants in the uppermost quintile tended to maintain their status in each of the age groups during a four-year follow-up. The magnitude of within-person variability of plasma lipids influences the ability to classify children into risk categories recommended by the National Cholesterol Education Program. ^

A multiplicative model for standardizing vital rates without using external standards

Standardization is a common method for adjusting confounding factors when comparing two or more exposure category to assess excess risk. Arbitrary choice of standard population in standardization introduces selection bias due to healthy worker effect. Small sample in specific groups also poses problems in estimating relative risk and the statistical significance is problematic. As an alternative, statistical models were proposed to overcome such limitations and find adjusted rates. In this dissertation, a multiplicative model is considered to address the issues related to standardized index namely: Standardized Mortality Ratio (SMR) and Comparative Mortality Factor (CMF). The model provides an alternative to conventional standardized technique. Maximum likelihood estimates of parameters of the model are used to construct an index similar to the SMR for estimating relative risk of exposure groups under comparison. Parametric Bootstrap resampling method is used to evaluate the goodness of fit of the model, behavior of estimated parameters and variability in relative risk on generated sample. The model provides an alternative to both direct and indirect standardization method. ^

Development and Characterization of an in vitro Four-species Anaerobic Dental Biofilm Model

Dental caries is the most common chronic disease worldwide. It is characterized by the demineralization of tooth enamel caused by acid produced by cariogenic dental bacteria growing on tooth surfaces, termed bacterial biofilms. Cariogenesis is a complex biological process that is influence by multiple factors and is not attributed to a sole causative agent. Instead, caries is associated with multispecies microbial biofilm communities composed of some bacterial species that directly influence the development of a caries lesion and other species that are seemingly benign but must contribute to the community in an uncharacterized way. Clinical analysis of dental caries and its microbial populations is challenging due to many factors including low sensitivity of clinical measurement tools, variability in saliva chemistry, and variation in the microbiota. Our laboratory has developed an in vitro anaerobic biofilm model for dental carries to facilitate both clinical and basic research-based analyses of the multispecies dynamics and individual factors that contribute to cariogenicity. The rational for development of this system was to improve upon the current models that lack key elements. This model places an emphasis on physiological relevance and ease of maintenance and reproducibility. The uniqueness of the model is based on integrating four critical elements: 1) a biofilm community composed of four distinct and representative species typically associated with dental caries, 2) a semi-defined synthetic growth medium designed to mimic saliva, 3) physiologically relevant biofilm growth substrates, and 4) a novel biofilm reactor device designed to facilitate the maintenance and analysis. Specifically, human tooth sections or hydroxyapatite discs embedded into poly(methyl methacrylate) (PMMA) discs are incubated for an initial 24 hr in a static inverted removable substrate (SIRS) biofilm reactor at 37°C under anaerobic conditions in artificial saliva (CAMM) without sucrose in the presence of 1 X 106 cells/ml of each Actinomyces odontolyticus, Fusobacterium nucleatum, Streptococcus mutans, and Veillonella dispar. During days 2 and 3 the samples are maintained continually in CAMM with various exposures to 0.2% sucrose; all of the discs are transferred into fresh medium every 24 hr. To validate that this model is an appropriate in vitro representation of a caries-associated multispecies biofilm, research aims were designed to test the following overarching hypothesis: an in vitro anaerobic biofilm composed of four species (S. mutans, V. dispar, A. odontolyticus, and F. nucleatum) will form a stable biofilm with a community profile that changes in response to environmental conditions and exhibits a cariogenic potential. For these experiments the biofilms as described above were exposed on days 2 and 3 to either CAMM lacking sucrose (no sucrose), CAMM with 0.2% sucrose (constant sucrose), or were transferred twice a day for 1 hr each time into 0.2% sucrose (intermittent sucrose). Four types of analysis were performed: 1) fluorescence microscopy of biofilms stained with Syto 9 and hexidium idodine to determine the biofilm architecture, 2) quantitative PCR (qPCR) to determine the cell number of each species per cm2, 3) vertical scanning interferometry (VSI) to determine the cariogenic potential of the biofilms, and 4) tomographic pH imaging using radiometric fluorescence microscopy after exposure to pH sensitive nanoparticles to measure the micro-environmental pH. The qualitative and quantitative results reveal the expected dynamics of the community profile when exposed to different sucrose conditions and the cariogenic potential of this in vitro four-species anaerobic biofilm model, thus confirming its usefulness for future analysis of primary and secondary dental caries.

Ocean temperature response to idealized Gleissberg and de Vries solar cycles in a comprehensive climate model

The ~90-year Gleissberg and ~200-year de Vries cycles have been identified as two distinctive quasi-periodic components of Holocene solar activity. Evidence exists for the impact of such multi-decadal to centennial-scale variability in total solar irradiance (TSI) on climate, but concerning the ocean, this evidence is mainly restricted to the surface response. Here we use a comprehensive global climate model to study the impact of idealized solar forcing, representing the Gleissberg and de Vries cycles, on global ocean potential temperature at different depth levels, after a recent proxy record indicates a signal of TSI anomalies in the northeastern Atlantic at mid-depth. Potential impacts of TSI anomalies on deeper oceanic levels are climatically relevant due to their possible effect on ocean circulation by altering water mass characteristics. Simulated solar anomalies are shown to penetrate the ocean down to at least deep-water levels. Despite the fact that the two forcing periods differ only by a factor of ~2, the spatial pattern of response is significantly distinctive between the experiments, suggesting different mechanisms for solar signal propagation. These are related to advection by North Atlantic Deep Water flow (200-year forcing), and barotropic adjustment in the South Atlantic in response to a latitudinal shift of the westerly wind belt (90-year forcing).

Case studies of the effects of a total solar eclipse on weather with varying degrees of cloud cover using a local numerical weather prediction model

The importance of renewable energies for the European electricity market is growing rapidly. This presents transmission grids and the power market in general with new challenges which stem from the higher spatiotemporal variability of power generation. This uncertainty is due to the fact that renewable power production results from weather phenomena, thus making it difficult to plan and control. We present a sensitivity study of a total solar eclipse in central Europe in March. The weather in Germany and Europe was modeled using the German Weather Service's local area models COSMO-DE and COSMO-EU, respectively (http://www.cosmo-model.org/). The simulations were performed with and without considering a solar eclipse for the following 3 situations: 1. An idealized, clear-sky situation for the entire model area (Europe, COSMO-EU) 2. A real weather situation with mostly cloudy skies (Germany, COSMO-DE) 3. A real weather situation with mostly clear skies (Germany, COSMO-DE) The data should help to evaluate the effects of a total solar eclipse on the weather in the planetary boundary layer. The results show that a total solar eclipse has significant effects particularly on the main variables for renewable energy production, such as solar irradiation and temperature near the ground.

Terrain model of the eastern slope of the Porcupine Seabight (50 m grid size)

The topography of the eastern margin of the Porcupine Seabight was surveyed in June 2000 utilizing swath bathymetry. The survey was carried out during RV Polarstern cruise ANT XVII/4 as part of the GEOMOUND project. The main objective was to map and investigate the seafloor topography of this region. The investigated area contains a variability of morphological features such as deep sea channels and giant mounds. The survey was planned and realized on the basis of existing data so as to guarantee the complete coverage of the margin. In order to achieve a resolution of the final digital terrain model (DTM) that meets the project demands, data processing was adjusted accordingly. The grid spacing of the DTM was set to 50 m and an accuracy better than 1% of the water depth was achieved for 96% of the soundings.

Age model for the time between 3.45 and 2.45 Ma of ODP Site 189-1172

Calcareous nannoplankton assemblages and benthic d18O isotopes of Pliocene deep-sea sediments of ODP site 1172 (East of Tasmania) have been studied to improve our knowledge of the Southern Ocean paleoceanography. Our study site is located just north of the Subtropical Front (STF), an ideal setting to monitor migrations of the STF during our study period, between 3.45 and 2.45 Ma. The assemblage identified at ODP site 1172 has been interpreted as characteristic for the transitional zone water mass, located south of the STF, based on: (i) the low abundances (< 1%) of subtropical taxa, (ii) relatively high percentages of Coccolithus pelagicus, a subpolar type species, (iii) abundances from 2-10% of Calcidiscus leptoporus, a species that frequently inhabits the zone south of the STF and (iv) the high abundances of small Noelaerhabdaceae which at present dominates the zone south of the STF. Across our interval the calcareous nannoplankton manifests glacial-interglacial variability. We have identified cold events, characterized by high abundances of C. pelagicus which coincide with glacial periods, except during G7. After 3.1 Ma cold events are more frequent, in concordance with global cooling trends. Around 2.75 Ma, the interglacial stage G7 is characterized by anomalous low temperatures which most likely are linked to definite closure of the Central American Seaway (CAS), an event that is believed to have had global consequences. A gradual increase of very small Reticulofenestra across our section marks a significant trend in the small Noelaerhabdaceae species group and has been linked to a general enhanced mixing of the water column in agreement with previous studies. It is suggested that a rapid decline of small Gephyrocapsa after isotopic stage G7 might be related to the cooling observed in our study site after the closure of the CAS.

Trace metal concentration and age model of ODP Hole 165-1002C sediments

Titanium and iron concentration data from the anoxic Cariaco Basin, off the Venezuelan coast, can be used to infer variations in the hydrological cycle over northern South America during the past 14,000 years with subdecadal resolution. Following a dry Younger Dryas, a period of increased precipitation and riverine discharge occurred during the Holocene 'thermal maximum'. Since ~5400 years ago, a trend toward drier conditions is evident from the data, with high-amplitude fluctuations and precipitation minima during the time interval 3800 to 2800 years ago and during the 'Little Ice Age'. These regional changes in precipitation are best explained by shifts in the mean latitude of the Atlantic Intertropical Convergence Zone (ITCZ), potentially driven by Pacific-based climate variability. The Cariaco Basin record exhibits strong correlations with climate records from distant regions, including the high-latitude Northern Hemisphere, providing evidence for global teleconnections among regional climates.