Factors associated with high anticholinergic burden in aging adults with intellectual disabilities:a cross-sectional study

Background: Anticholinergic (AC) medications are associated with cognitive and functional decline in older people, with risk of adverse outcomes increasing with increasing AC exposure. Older people with intellectual disabilities are at increased risk of high AC exposure owing to higher prevalence of multimorbidity, particularly psychiatric morbidities. Objectives: The aims of this study were to determine individual’s AC exposure using the AC cognitive burden (ACB) scale, identify therapeutic classes contributing to burden and determine clinical and demographic factors associated with two levels of AC exposure (ACB score 1–4, ACB 5+). Methods: Cross-sectional (self-report/proxy report)medication data were drawn from Wave 1 of the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing, a study on ageing of 753nationally representative people with ID aged over40 randomly selected from the National Intellectual Disability Database. Medication data were available for 736 (98%). Each individual’s cumulative AC exposure was calculated using the ACB. Multinomiallogistic regression was performed identifying clinical and demographic factors associated with ACB score1–4, and ACB 5+. Results: In the eligible population of 736 participants(mean (±SD) age 54.1 (±8.8) years,55% female), 522(70.9%) were exposed to an ACB medicine (ACB 1+); 214 (29%) had an ACB score of 5+; mean total ACB score= 4.5 (±3.0). Antipsychotics accounted for35.6% of the cumulative ACB score. Age over 65yearswas associated with increased likelihood of both levels of AC exposure (ACB 1–4—adjusted OR 3.28; 95%CI 1.49–7.25, ACB 5+—adjusted OR 3.08; 95%CI1.21–7.63) and having a mental health condition(ACB 1–4—adjusted OR 9.79; 95%CI 5.63–17.02, ACB 5+—adjusted OR 23.74; 95%CI 12.29–45.83). Conclusions: Using a simple cumulative measure proved an effective means to capture total burden and established that AC exposure was high and associated with older age and mental health morbidity. This highlights need for comprehensive medication reviews for older people with intellectual disabilities.

Reading comprehension and mathematical concept acquisition through the use of math stories with bilingual children

Math storybooks are picture books in which the understanding of mathematical concepts is central to the comprehension of the story. Math stories have provided useful opportunities for children to expand their skills in the language arts area and to talk about mathematical factors that are related to their real lives. The purpose of this study was to examine bilingual children's reading and math comprehension of the math storybooks. ^ The participants were randomly selected from two Korean schools and two public elementary schools in Miami, Florida. The sample consisted of 63 Hispanic American and 43 Korean American children from ages five to seven. A 2 x 3 x (2) mixed-model design with two between- and one within-subjects variable was used to conduct this study. The two between-subjects variables were ethnicity and age, and the within-subjects variable was the subject area of comprehension. Subjects were read the three math stories individually, and then they were asked questions related to reading and math comprehension. ^ The overall ANOVA using multivariate tests was conducted to evaluate the factor of subject area for age and ethnicity. As follow-up tests for a significant main effect and a significant interaction effect, pairwise comparisons and simple main effect tests were conducted, respectively. ^ The results showed that there were significant ethnicity and age differences in total comprehension scores. There were also age differences in reading and math comprehension, but no significant differences were found in reading and math by ethnicity. Korean American children had higher scores in total comprehension than those of Hispanic American children, and they showed greater changes in their comprehension skills at the younger ages, from five to six, whereas Hispanic American children showed greater changes at the older ages, from six to seven. Children at ages five and six showed higher scores in reading than in math, but no significant differences between math and reading comprehension scores were found at age seven. ^ Through schooling with integrated instruction, young bilingual children can move into higher levels of abstraction and concepts. This study highlighted bilingual children's general nature of thinking and showed how they developed reading and mathematics comprehension in an integrated process. ^

Theological reflection at work: A phenomenological study of learning processes

Using the learning descriptions of graduates of a graduate ministry program, the mechanisms of interactions between the knowledge facets in learning processes were explored and described. The intent of the study was to explore how explicit, implicit, and emancipatory knowledge facets interacted in the learning processes at or about work. The study provided empirical research on Yang's (2003) holistic learning theory. ^ A phenomenological research design was used to explore the essence of knowledge facet interactions. I achieved epoche through the disclosure of assumptions and a written self-experience to bracket biases. A criterion based, stratified sampling strategy was used to identify participants. The sample was stratified by graduation date. The sample consisted of 11 participants and was composed primarily of married (n = 9), white, non-Hispanic (n = 10), females (n = 9), who were Roman Catholic (n = 9). Professionally, the majority of the group were teachers or professors (n = 5). ^ A semi-structured interview guide with scheduled and unscheduled probes was used. Each approximately 1-hour long interview was digitally recorded and transcribed. The transcripts were coded using a priori codes from holistic learning theory and one emergent code. The coded data were analyzed by identifying patterns, similarities, and differences under each code and then between codes. Steps to increase the trustworthiness of the study included member checks, coding checks, and thick descriptions of the data. ^ Five themes were discovered including (a) the difficulty in describing interactions between knowledge facets; (b) actual mechanisms of interactions between knowledge facets; (c) knowledge facets initiating learning and dominating learning processes; (d) the dangers of one-dimensional learning or using only one knowledge facet to learn; and (e) the role of community in learning. The interpretation confirmed, extended, and challenged holistic learning theory. Mechanisms of interaction included knowledge facets expressing, informing, changing, and guiding one another. Implications included the need for a more complex model of learning and the value of seeing spirituality in the learning process. The study raised questions for future research including exploring learning processes with people from non-Christian faith traditions or other academic disciplines and the role of spiritual identity in learning. ^

Controlled growth of carbon nanotubes for high performance nanoelectronics

Unique electrical and mechanical properties of single-walled carbon nanotubes (SWNTs) have made them one of the most promising candidates for next-generation nanoelectronics. Efficient utilization of the exceptional properties of SWNTs requires controlling their growth direction (e.g., vertical, horizontal) and morphologies (e.g., straight, junction, coiled). ^ In this dissertation, the catalytic effect on the branching of SWNTs, Y-shaped SWNTs (Y-SWNTs), was investigated. The formation of Y-shaped branches was found to be dependent on the composition of the catalysts. Easier carbide formers have a strong tendency to attach to the sidewall of SWNTs and thus enhance the degree of branching. Y-SWNTs based field-effect transistors (FETs) were fabricated and modulated by the metallic branch of the Y-SWNTs, exhibiting ambipolar characteristics at room temperature. A subthreshold swing of 700 mV/decade and an on/off ratio of 105 with a low off-state current of 10-13 A were obtained. The transport phenomena associated with Y- and cross-junction configurations reveals that the conduction mechanism in the SWNT junctions is governed by thermionic emission at T > 100 K and by tunneling at T < 100 K. ^ Furthermore, horizontally aligned SWNTs were synthesized by the controlled modification of external fields and forces. High performance carbon nanotube FETs and logic circuit were demonstrated utilizing the aligned SWNTs. It is found that the hysteresis in CNTFETs can be eliminated by removing absorbed water molecules on the CNT/SiO2 interface by vacuum annealing, hydrophobic surface treatment, and surface passivation. SWNT “serpentines” were synthesized by utilization of the interaction between drag force from gas flow and Van der Waals force with substrates. The curvature of bent SWNTs could be tailored by adjusting the gas flow rate, and changing the gas flow direction with respect to the step-edges on a single-crystal quartz substrate. Resistivity of bent SWNTs was observed to increase with curvature, which can be attributed to local deformations and possible chirality shift at curved part. ^ Our results show the successful synthesis of SWNTs having controllable morphologies and directionality. The capability of tailoring the electrical properties of SWNTs makes it possible to build an all-nanotube device by integrating SWNTs, having different functionalities, into complex circuits. ^

Healthy Eating Index and Alternate Healthy Eating Index among Haitian Americans and African Americans with and without Type 2 Diabetes

Ethnicities within Black populations have not been distinguished in most nutrition studies. We sought to examine dietary differences between African Americans (AA) and Haitian Americans (HA) with and without type 2 diabetes using the Healthy Eating Index, 2005 (HEI-05), and the Alternate Healthy Eating Index (AHEI). The design was cross-sectional (225 AA, 246 HA) and recruitment was by community outreach. The eating indices were calculated from data collected with the Harvard food-frequency questionnaire. African Americans had lower HEI-05 scores (−8.67, 13.1); , than HA. Haitian American females and AA males had higher AHEI than AA females and HA males, respectively, () adjusting for age and education. Participants with diabetes had higher adherence to the HEI-05 (1.78, 6.01), , and lower adherence to the AHEI (16.3, −3.19), , , than participants without diabetes. The findings underscore the importance of disaggregating ethnicities and disease state when assessing diet.

Annotated record of the detailed examination of Mn nodules recovered from the VA04 expedition (R/V Valdivia) in the Pacific Ocean

Twenty-four manganese nodules from the surface of the sea floor and fifteen buried nodules were studied. With three exceptions, the nodules were collected from the area covered by Valdivia Cruise VA 04 some 1200 nautical miles southeast of Hawaii. Age determinations were made using the ionium method. In order to get a true reproduction of the activity distribution in the nodules, they were cut in half and placed for one month on nuclear emulsion plates to determine the alpha-activity of the ionium and its daughter products. Special methods of counting the alpha-tracks resolution to depth intervals of 0.125 mm. For the first time it was possible to resolve zones of rapid growth (impulse growth) with growth rates, s > 50 mm/106 yr and interruptions in growth. With few exceptions the average rate of growth of all nodules was surprisingly uniform at 4-9 mm/10 yr. No growth could be recognized radioactively in the buried nodules. One exceptional nodule has had recent impulse growth and, in the material formed, the ionium is not yet in equilibrium with its daughter products. Individual layers in one nodule from the Indian Ocean could be dated and an average time interval of t = 2600±400 yr was necessary to form one layer. The alternation between iron and manganese-rich parts of the nodules was made visible by colour differences resulting from special treatment of cut surfaces with HCl vapour. The zones of slow growth of one nodule are relatively enriched in iron. Earlier attempts to find paleomagnetic reversals in manganese nodules have been continued. Despite considerable improvement in areal resolution, reversals were not detected in the nodules studied. Comparisons of the surface structure, microstructure in section and the radiometric dating show that there are erosion surfaces and growth surfaces on the outer surfaces of the manganese nodules. The formation of cracks in the nodules was studied in particular. The model of age-dependent nodule shrinkage and cracking surprisingly indicates that the nodules break after exceeding a certain age and/or size. Consequently, the breaking apart of manganese nodules is a continuous process not of catastrophic or discontinuous origin. The microstructure of the nodules exhibits differences in the mechanism of accretion and accretion rate of material, shortly referred to as accretion form. Thus non-directional growth inside the nodules as well as a directional growth may be observed. Those nodules with large accretion forms have grown faster than smaller ones. Consequently, parallel layers indicate slow growth. The upper surfaces of the nodules, protruding into the bottom water appear to be more prone to growth disturbances than the lower surfaces, immersed in the sediment. Features of some nodules show, that as they develop, they neither turned nor rolled. Yet unknown is the mechanism that keeps the nodules at the surface during continuous sedimentation. All in all, the nodules remain the objects of their own distinctive problems. The hope of using them as a kind of history book still seems to be very remote.

Environmental controls on bioturbation processes in marine benthic habits

Through bioturbation, the macrofauna mediate chemical, physical and biological processes in marine benthic ecosystems. Because of the importance of bioturbation as ecosystem mediator, various studies have been conducted on bioturbation intensity and depth, and the relation of bioturbation processes to environmental condition and ecosystem state. This thesis builds on those previous studies, using a standard field and analytical protocol and by expanding the geographical scale to three climatic regions along Canada’s East Coast and Arctic margins, the Arctic Archipelago, the coastal Subarctic (Labrador Fjords), and the temperate continental climate zone (Gulf of Maine and adjacent Scotian shelf/slope). This Ph.D. study provides a comprehensive assessment of environmental influences on bioturbation along gradients in latitude and ocean depth. Bioturbation intensity, mixing depth, and bioturbation structures were studied in relation to the quantity and quality of potential food sources (organic matter) and substrate characteristics to gain an understanding of the environmental controls on bioturbation in these regions. The three main research chapters of this thesis are divided based on the contrasting climatic and geographical regions studied. The analytical approach included seabed sampling with a boxcorer, describing the sedimentary fabric and bioturbation structures by X-radiography, estimating bioturbation intensity and depth applying a biodiffusion model to particle tracer profiles of ²¹⁰Pbₓs, ²²⁸Thₓs, ²³⁴Thₓs, and chlorophyll-a, and analyzing benthic organic matter and substrate characteristics. Strong regional and cross-climatic relations of bioturbation processes with combinations of environmental factors were observed. In particular, bioturbation depth and the vertical extent of bioturbation structures responded to the environmental patterns observed and, therefore, represented potentially applicable predictors of environmental conditions and ecosystem state. The results of this Ph.D. study may be further extended to other geographical regions with similar environmental characteristics to predict the effects of benthic habitat alterations through environmental stresses on a global scale. Integrated with biological data produced by fellow CHONe scientists the presented data may provide valuable information about functional roles of macrofaunal species and community traits in marine benthic ecosystems along Canada’s extensive East Coast and Arctic margins.

Seawater carbonate chemistry and growth, carbon acquisition, and species interaction of Antarctic phytoplankton species in a laboratory experiment

Despite the fact that ocean acidification is considered to be especially pronounced in the Southern Ocean, little is known about CO2-dependent physiological processes and the interactions of Antarctic phytoplankton key species. We therefore studied the effects of CO2 partial pressure (PCO2) (16.2, 39.5, and 101.3 Pa) on growth and photosynthetic carbon acquisition in the bloom-forming species Chaetoceros debilis, Pseudo-nitzschia subcurvata, Fragilariopsis kerguelensis, and Phaeocystis antarctica. Using membrane-inlet mass spectrometry, photosynthetic O2 evolution and inorganic carbon (Ci) fluxes were determined as a function of CO2 concentration. Only the growth of C. debilis was enhanced under high PCO2. Analysis of the carbon concentrating mechanism (CCM) revealed the operation of very efficient CCMs (i.e., high Ci affinities) in all species, but there were species-specific differences in CO2-dependent regulation of individual CCM components (i.e., CO2 and uptake kinetics, carbonic anhydrase activities). Gross CO2 uptake rates appear to increase with the cell surface area to volume ratios. Species competition experiments with C. debilis and P. subcurvata under different PCO2 levels confirmed the CO2-stimulated growth of C. debilis observed in monospecific incubations, also in the presence of P. subcurvata. Independent of PCO2, high initial cell abundances of P. subcurvata led to reduced growth rates of C. debilis. For a better understanding of future changes in phytoplankton communities, CO2-sensitive physiological processes need to be identified, but also species interactions must be taken into account because their interplay determines the success of a species.

Vacuum spacetimes with constant Weyl eigenvalues

Einstein spacetimes (that is vacuum spacetimes possibly with a non-zero cosmological constant A) with constant non-zero Weyl eigenvalues are considered. For type Petrov II & D this assumption allows one to prove that the non-repeated eigenvalue necessarily has the value 2A/3 and it turns out that the only possible spacetimes are some Kundt-waves considered by Lewandowski which are type II and a Robinson-Bertotti solution of type D. For Petrov type I the only solution turns out to be a homogeneous pure vacuum solution found long ago by Petrov using group theoretic methods. These results can be summarised by the statement that the only vacuum spacetimes with constant Weyl eigenvalues are either homogeneous or are Kundt spacetimes. This result is similar to that of Coley et al. who proved their result for general spacetimes under the assumption that all scalar invariants constructed from the curvature tensor and all its derivatives were constant.

Immunity and Arginine Deprivation in Alzheimer's Disease

The pathogenesis of Alzheimer’s disease (AD) is a critical unsolved question, and while recent studies have demonstrated a strong association between altered brain immune responses and disease progression, the mechanistic cause of neuronal dysfunction and death is unknown. We have previously described the unique CVN-AD mouse model of AD, in which immune-mediated nitric oxide is lowered to mimic human levels, resulting in a mouse model that demonstrates the cardinal features of AD, including amyloid deposition, hyperphosphorylated and aggregated tau, behavioral changes and age-dependent hippocampal neuronal loss. Using this mouse model, we studied longitudinal changes in brain immunity in relation to neuronal loss and, contrary to the predominant view that AD pathology is driven by pro-inflammatory factors, we find that the pathology in CVN-AD mice is driven by local immune suppression. Areas of hippocampal neuronal death are associated with the presence of immunosuppressive CD11c+ microglia and extracellular arginase, resulting in arginine catabolism and reduced levels of total brain arginine. Pharmacologic disruption of the arginine utilization pathway by an inhibitor of arginase and ornithine decarboxylase protected the mice from AD-like pathology and significantly decreased CD11c expression. Our findings strongly implicate local immune-mediated amino acid catabolism as a novel and potentially critical mechanism mediating the age-dependent and regional loss of neurons in humans with AD.

There is a large interest in identifying, lineage tracing, and determining the physiologic roles of monophagocytes in Alzheimer’s disease. While Cx3cr1 knock-in fluorescent reporting and Cre expressing mice have been critical for studying neuroimmunology, mice that are homozygous null or hemizygous for CX3CR1 have perturbed neural development and immune responses. There is, therefore, a need for similar tools in which mice are CX3CR1+/+. Here, we describe a mouse where Cre is driven by the Cx3cr1 promoter on a bacterial artificial chromosome (BAC) transgene (Cx3cr1-CreBT) and the Cx3cr1 locus is unperturbed. Similarly to Cx3cr1-Cre knock-in mice, these mice express Cre in Ly6C-, but not Ly6C+, monocytes and tissue macrophages, including microglia. These mice represent a novel tool that maintains the Cx3cr1 locus while allowing for selective gene targeting in monocytes and tissue macrophages.

The study of immunity in Alzheimer’s requires the ability to identify and quantify specific immune cell subsets by flow cytometry. While it is possible to identify lymphocyte subsets based on cell lineage-specific markers, the lack of such markers in brain myeloid cell subsets has prevented the study of monocytes, macrophages and dendritic cells. By improving on tissue homogenization, we present a comprehensive protocol for flow cytometric analysis, that allows for the identification of several cell types that have not been previously identified by flow cytometry. These cell types include F4/80hi macrophages, which may be meningeal macrophages, IA/IE+ macrophages, which may represent perivascular macrophages, and dendritic cells. The identification of these cell types now allows for their study by flow cytometry in homeostasis and disease.

Bayesian Inference in Large-scale Problems

Many modern applications fall into the category of "large-scale" statistical problems, in which both the number of observations n and the number of features or parameters p may be large. Many existing methods focus on point estimation, despite the continued relevance of uncertainty quantification in the sciences, where the number of parameters to estimate often exceeds the sample size, despite huge increases in the value of n typically seen in many fields. Thus, the tendency in some areas of industry to dispense with traditional statistical analysis on the basis that "n=all" is of little relevance outside of certain narrow applications. The main result of the Big Data revolution in most fields has instead been to make computation much harder without reducing the importance of uncertainty quantification. Bayesian methods excel at uncertainty quantification, but often scale poorly relative to alternatives. This conflict between the statistical advantages of Bayesian procedures and their substantial computational disadvantages is perhaps the greatest challenge facing modern Bayesian statistics, and is the primary motivation for the work presented here.

Two general strategies for scaling Bayesian inference are considered. The first is the development of methods that lend themselves to faster computation, and the second is design and characterization of computational algorithms that scale better in n or p. In the first instance, the focus is on joint inference outside of the standard problem of multivariate continuous data that has been a major focus of previous theoretical work in this area. In the second area, we pursue strategies for improving the speed of Markov chain Monte Carlo algorithms, and characterizing their performance in large-scale settings. Throughout, the focus is on rigorous theoretical evaluation combined with empirical demonstrations of performance and concordance with the theory.

One topic we consider is modeling the joint distribution of multivariate categorical data, often summarized in a contingency table. Contingency table analysis routinely relies on log-linear models, with latent structure analysis providing a common alternative. Latent structure models lead to a reduced rank tensor factorization of the probability mass function for multivariate categorical data, while log-linear models achieve dimensionality reduction through sparsity. Little is known about the relationship between these notions of dimensionality reduction in the two paradigms. In Chapter 2, we derive several results relating the support of a log-linear model to nonnegative ranks of the associated probability tensor. Motivated by these findings, we propose a new collapsed Tucker class of tensor decompositions, which bridge existing PARAFAC and Tucker decompositions, providing a more flexible framework for parsimoniously characterizing multivariate categorical data. Taking a Bayesian approach to inference, we illustrate empirical advantages of the new decompositions.

Latent class models for the joint distribution of multivariate categorical, such as the PARAFAC decomposition, data play an important role in the analysis of population structure. In this context, the number of latent classes is interpreted as the number of genetically distinct subpopulations of an organism, an important factor in the analysis of evolutionary processes and conservation status. Existing methods focus on point estimates of the number of subpopulations, and lack robust uncertainty quantification. Moreover, whether the number of latent classes in these models is even an identified parameter is an open question. In Chapter 3, we show that when the model is properly specified, the correct number of subpopulations can be recovered almost surely. We then propose an alternative method for estimating the number of latent subpopulations that provides good quantification of uncertainty, and provide a simple procedure for verifying that the proposed method is consistent for the number of subpopulations. The performance of the model in estimating the number of subpopulations and other common population structure inference problems is assessed in simulations and a real data application.

In contingency table analysis, sparse data is frequently encountered for even modest numbers of variables, resulting in non-existence of maximum likelihood estimates. A common solution is to obtain regularized estimates of the parameters of a log-linear model. Bayesian methods provide a coherent approach to regularization, but are often computationally intensive. Conjugate priors ease computational demands, but the conjugate Diaconis--Ylvisaker priors for the parameters of log-linear models do not give rise to closed form credible regions, complicating posterior inference. In Chapter 4 we derive the optimal Gaussian approximation to the posterior for log-linear models with Diaconis--Ylvisaker priors, and provide convergence rate and finite-sample bounds for the Kullback-Leibler divergence between the exact posterior and the optimal Gaussian approximation. We demonstrate empirically in simulations and a real data application that the approximation is highly accurate, even in relatively small samples. The proposed approximation provides a computationally scalable and principled approach to regularized estimation and approximate Bayesian inference for log-linear models.

Another challenging and somewhat non-standard joint modeling problem is inference on tail dependence in stochastic processes. In applications where extreme dependence is of interest, data are almost always time-indexed. Existing methods for inference and modeling in this setting often cluster extreme events or choose window sizes with the goal of preserving temporal information. In Chapter 5, we propose an alternative paradigm for inference on tail dependence in stochastic processes with arbitrary temporal dependence structure in the extremes, based on the idea that the information on strength of tail dependence and the temporal structure in this dependence are both encoded in waiting times between exceedances of high thresholds. We construct a class of time-indexed stochastic processes with tail dependence obtained by endowing the support points in de Haan's spectral representation of max-stable processes with velocities and lifetimes. We extend Smith's model to these max-stable velocity processes and obtain the distribution of waiting times between extreme events at multiple locations. Motivated by this result, a new definition of tail dependence is proposed that is a function of the distribution of waiting times between threshold exceedances, and an inferential framework is constructed for estimating the strength of extremal dependence and quantifying uncertainty in this paradigm. The method is applied to climatological, financial, and electrophysiology data.

The remainder of this thesis focuses on posterior computation by Markov chain Monte Carlo. The Markov Chain Monte Carlo method is the dominant paradigm for posterior computation in Bayesian analysis. It has long been common to control computation time by making approximations to the Markov transition kernel. Comparatively little attention has been paid to convergence and estimation error in these approximating Markov Chains. In Chapter 6, we propose a framework for assessing when to use approximations in MCMC algorithms, and how much error in the transition kernel should be tolerated to obtain optimal estimation performance with respect to a specified loss function and computational budget. The results require only ergodicity of the exact kernel and control of the kernel approximation accuracy. The theoretical framework is applied to approximations based on random subsets of data, low-rank approximations of Gaussian processes, and a novel approximating Markov chain for discrete mixture models.

Data augmentation Gibbs samplers are arguably the most popular class of algorithm for approximately sampling from the posterior distribution for the parameters of generalized linear models. The truncated Normal and Polya-Gamma data augmentation samplers are standard examples for probit and logit links, respectively. Motivated by an important problem in quantitative advertising, in Chapter 7 we consider the application of these algorithms to modeling rare events. We show that when the sample size is large but the observed number of successes is small, these data augmentation samplers mix very slowly, with a spectral gap that converges to zero at a rate at least proportional to the reciprocal of the square root of the sample size up to a log factor. In simulation studies, moderate sample sizes result in high autocorrelations and small effective sample sizes. Similar empirical results are observed for related data augmentation samplers for multinomial logit and probit models. When applied to a real quantitative advertising dataset, the data augmentation samplers mix very poorly. Conversely, Hamiltonian Monte Carlo and a type of independence chain Metropolis algorithm show good mixing on the same dataset.

The impact of maternal inflammation and maternal stress in the regulation of neurodevelopment and physiological function

The mechanisms governing fetal development follow a tightly regulated pattern of progression such that interference at any one particular stage is likely to have consequences for all other stages of development in the physiological system that has been affected thereafter. These disturbances can take the form of many different events but two of the most common and widely implicated in causing detrimental effects to the developing fetus are maternal immune activation (MIA) and maternal stress. MIA has been shown to cause an increase in circulating proinflammatory cytokines in both the maternal and fetal circulation. This increase in proinflammatory mediators in the fetus is thought to occur by fetal production rather than through exchange between the maternal-fetal interface. In the case of maternal stress it is increased levels of stress related hormones such as cortisol/corticosterone which is thought to elicit the detrimental effects on fetal development. In the case of both maternal infection and stress the timing and nature of the insult generally dictates the severity and type of effects seen in affected offspring. We investigated the effect of a proinflammatory environment on neural precursor cells of which exposure resulted in a significant decrease in the normal rate of proliferation of NPCs in culture but did not have any effect on cell survival. These effects were seen to be age dependent. Using a restraint stress model we investigated the effects of prenatal stress on the development of a number of different physiological systems in the same cohort of animals. PNS animals exhibited a number of aberrant changes in cardiovascular function with altered responses to stress and hypertension, modifications in respiratory responses to hypercapnic and hypoxic challenges and discrepancies in gastrointestinal innervation. Taken together these findings suggest that both maternal infection and maternal stress are detrimental to the normal development of the fetus.

Radiocarbon dating, oxygen isotopes, and sea-level reconstruction of sediment core GeoB5844-2 from the northern end of the Red Sea

Based on a radiocarbon and paleomagnetically dated sediment record from the northern Red Sea and the exceptional sensitivity of the regional changes in the oxygen isotope composition of sea water to the sea-level-dependent water exchange with the Indian Ocean, we provide a new global sea-level reconstruction spanning the last glacial period. The sea-level record has been extracted from the temperature-corrected benthic stable oxygen isotopes using coral-based sea-level data as constraints for the sea-level/oxygen isotope relationship. Although, the general features of this millennial-scale sea-level records have strong similarities to the rather symmetric and gradual Southern Hemisphere climate patterns, we observe, in constrast to previous findings, pronounced sea level rises of up to 25 m to generally correspond with Northern Hemisphere warmings as recorded in Greenland ice-core interstadial intervals whereas sea-level lowstands mostly occur during cold phases. Corroborated by CLIMBER-2 model results, the close connection of millennial-scale sea-level changes to Northern Hemisphere temperature variations indicates a primary climatic control on the mass balance of the major Northern Hemisphere ice sheets and does not require a considerable Antarctic contribution.

Grain-size, lithic grains, foraminifera-derived and dinocyst-derived data of sediment core MD99-2281

The last glacial period was punctuated by abrupt climatic events with extrema known as Heinrich and Dansgaard-Oeschger events. These millennial events have been the subject of many paleoreconstructions and model experiments in the past decades, but yet the hydrological processes involved remain elusive. In the present work, high-resolution analyses were conducted on the 12-42 ka BP section of core MD99-2281 retrieved southwest of the Faeroe Islands, and combined with analyses conducted in two previous studies (Zumaque et al., 2012; Caulle et al., 2013). Such a multiproxy approach, coupling micropaleontological, geochemical and sedimentological analyses, allows us to track surface, subsurface, and deep hydrological processes occurring during these rapid climatic changes. Records indicate that the coldest episodes of the studied period (Greenland stadials and Heinrich stadials) were characterized by a strong stratification of surface waters. This surface stratification seems to have played a key role in the dynamics of subsurface and deep-water masses. Indeed, periods of high surface stratification are marked by a coupling of subsurface and deep circulations which sharply weaken at the beginning of stadials, while surface conditions progressively deteriorate throughout these cold episodes; conversely, periods of decreasing surface stratification (Greenland interstadials) are characterized by a coupling of surface and deep hydrological processes, with progressively milder surface conditions and gradual intensification of the deep circulation, while the vigor of the subsurface northward Atlantic flow remains constantly high. Our results also reveal different and atypical hydrological signatures during Heinrich stadials (HSs): while HS1 and HS4 exhibit a "usual" scheme with reduced overturning circulation, a relatively active North Atlantic circulation seems to have prevailed during HS2, and HS3 seems to have experienced a re-intensification of this circulation during the middle of the event. Our findings thus bring valuable information to better understand hydrological processes occurring in a key area during the abrupt climatic shifts of the last glacial period.

Lung clearance index in adults and children with cystic fibrosis

Background: Lung clearance index (LCI) has good clinimetric properties and an acceptable feasibility profile as a surrogate endpoint in Cystic Fibrosis (CF). Although most studies to date have been in children, increasing numbers of adults with CF also have normal spirometry. Further study of LCI as an endpoint in CF adults is required. Therefore, the purpose of this study was to determine the clinimetric properties of LCI over the complete age range of people with CF. Methods: Clinically stable adults and children with CF and age matched healthy controls were recruited. Results: LCI and spirometry data for 110 CF subjects and 61 controls were collected at a stable visit. CF Questionnaire-Revised (CFQ-R) was completed by 80/110 CF subjects. Fifty-six CF subjects completed a second stable visit. The LCI CV% was 4.1% in adults and 6.3% in children with CF. The coefficient of repeatability of LCI was 1.2 in adults and 1.3 in children. In both adults and children, LCI (AUCROC=0.93 and 0.84) had greater combined sensitivity and specificity to discriminate between people with CF and controls compared to FEV1 (AUCROC=0.88 and 0.60) and FEF25-75 (AUCROC=0.87 and 0.68). LCI correlated significantly with the CFQ-R treatment burden in adults (r=-0.37; p<0.01) and children (r=-0.50; p<0.01). Washout tests were successful in 90% of CF subjects and were perceived as comfortable and easy to perform in both adults and children. Conclusions: These data support the use of LCI as a surrogate outcome measure in CF clinical trials in adults as well as children.