Repeated measures of body mass index and C-reactive protein in relation to all-cause mortality and cardiovascular disease: Results from the consortium on health and ageing network of cohorts in Europe and the United States (CHANCES)

Obesity has been linked with elevated levels of C-reactive protein (CRP), and both have been associated with increased risk of mortality and cardiovascular disease (CVD). Previous studies have used a single ‘baseline’ measurement and such analyses cannot account for possible changes in these which may lead to a biased estimation of risk. Using four cohorts from CHANCES which had repeated measures in participants 50 years and older, multivariate time-dependent Cox proportional hazards was used to estimate hazard ratios (HR) and 95 % confidence intervals (CI) to examine the relationship between body mass index (BMI) and CRP with all-cause mortality and CVD. Being overweight (≥25–<30 kg/m2) or moderately obese (≥30–<35) tended to be associated with a lower risk of mortality compared to normal (≥18.5–<25): ESTHER, HR (95 % CI) 0.69 (0.58–0.82) and 0.78 (0.63–0.97); Rotterdam, 0.86 (0.79–0.94) and 0.80 (0.72–0.89). A similar relationship was found, but only for overweight in Glostrup, HR (95 % CI) 0.88 (0.76–1.02); and moderately obese in Tromsø, HR (95 % CI) 0.79 (0.62–1.01). Associations were not evident between repeated measures of BMI and CVD. Conversely, increasing CRP concentrations, measured on more than one occasion, were associated with an increasing risk of mortality and CVD. Being overweight or moderately obese is associated with a lower risk of mortality, while CRP, independent of BMI, is positively associated with mortality and CVD risk. If inflammation links CRP and BMI, they may participate in distinct/independent pathways. Accounting for independent changes in risk factors over time may be crucial for unveiling their effects on mortality and disease morbidity.

CCAAT/enhancer binding protein α predicts poorer prognosis and prevents energy starvation-induced cell death in hepatocellular carcinoma

CCAAT enhancer binding protein α (C/EBPα) plays an essential role in cellular differentiation, growth, and energy metabolism. Here, we investigate the correlation between C/EBPα and hepatocellular carcinoma (HCC) patient outcomes and how C/EBPα protects cells against energy starvation. Expression of C/EBPα protein was increased in the majority of HCCs examined (191 pairs) compared with adjacent nontumor liver tissues in HCC tissue microarrays. Its upregulation was correlated significantly with poorer overall patient survival in both Kaplan-Meier survival (P = 0.017) and multivariate Cox regression (P = 0.028) analyses. Stable C/EBPα-silenced cells failed to establish xenograft tumors in nude mice due to extensive necrosis, consistent with increased necrosis in human C/EBPα-deficient HCC nodules. Expression of C/EBPα protected HCC cells in vitro from glucose and glutamine starvation-induced cell death through autophagy-involved lipid catabolism. Firstly, C/EBPα promoted lipid catabolism during starvation, while inhibition of fatty acid beta-oxidation significantly sensitized cell death. Secondly, autophagy was activated in C/EBPα-expressing cells, and the inhibition of autophagy by ATG7 knockdown or chloroquine treatment attenuated lipid catabolism and subsequently sensitized cell death. Finally, we identified TMEM166 as a key player in C/EBPα-mediated autophagy induction and protection against starvation.

CONCLUSION: The C/EBPα gene is important in that it links HCC carcinogenesis to autophagy-mediated lipid metabolism and resistance to energy starvation; its expression in HCC predicts poorer patient prognosis.

Neural basis of language switching in the brain: fMRI evidence from Korean-Chinese early bilinguals

Using fMRI, we conducted two types of property generation task that involved language switching, with early bilingual speakers of Korean and Chinese. The first is a more conventional task in which a single language (L1 or L2) was used within each trial, but switched randomly from trial to trial. The other consists of a novel experimental design where language switching happens within each trial, alternating in the direction of the L1/L2 translation required. Our findings support a recently introduced cognitive model, the 'hodological' view of language switching proposed by Moritz-Gasser and Duffau. The nodes of a distributed neural network that this model proposes are consistent with the informative regions that we extracted in this study, using both GLM methods and Multivariate Pattern Analyses: the supplementary motor area, caudate, supramarginal gyrus and fusiform gyrus and other cortical areas. 

Preschool Children's Awareness of and Attitudes Toward Difference: A Study of 3- and 4-Year-Old Children in Northern Ireland

This paper presents the findings of a large-scale survey (n = 1,049) of the ethnic awareness and attitudes of 3-4 year old children in Northern Ireland. In drawing upon and applying Bourdieu’s notion of habitus, the paper demonstrates how even at this age, the children are already beginning to embody and internalize the cultural habits and dispositions of their respective ethnic groups. This was found in relation to the children’s: friendships choices; preferences for particular national flags; and dispositions towards specific sports associated with their respective communities. Informed by the work of Bourdieu, the paper concludes by arguing for the need for greater use of quantitative methods employing multivariate and multilevel statistical analyses and for these to be based on a more open and meaningful engagement with the findings of indepth qualitative and ethnographic research in this area.

A multivariate analysis of beta diversity across organisms and environments

We examined variability in hierarchical beta diversity across ecosystems, geographical gradients, and organism groups using multivariate spatial mixed modeling analysis of two independent data sets. The larger data set comprised reported ratios of regional species richness (RSR) to local species richness (LSR) and the second data set consisted of RSR: LSR ratios derived from nested species-area relationships. There was a negative, albeit relatively weak, relationship between beta diversity and latitude. We found only relatively subtle differences in beta diversity among the realms, yet beta diversity was lower in marine systems than in terrestrial or freshwater realms. Beta diversity varied significantly among organisms' major characteristics such as body mass, trophic position, and dispersal type in the larger data set. Organisms that disperse via seeds had highest beta diversity, and passively dispersed organisms showed the lowest beta diversity. Furthermore, autotrophs had lower beta diversity than organisms higher up the food web; omnivores and carnivores had consistently higher beta diversity. This is evidence that beta diversity is simultaneously controlled by extrinsic factors related to geography and environment, and by intrinsic factors related to organism characteristics.

Population genetic analyses reveal distinct geographical blooms of the jellyfish Rhizostoma octopus (Scyhpozoa)

Understanding the spatial integrity and connectivity of jellyfish blooms is important for ecologists and coastal stakeholders alike. Previous studies have shown that the distribution of jellyfish blooms can display a marked consistency in space and time, suggesting that such patterns cannot be attributed to passive processes alone. In the present study, we used a combination of microsatellite markers and mitochondrial cytochrome oxidase I sequences to investigate genetic structuring of the scyphozoan jellyfish Rhizostoma octopus in the Irish and Celtic Seas. The mitochondrial data indicated far higher levels of population differentiation than the microsatellites: ΦST[MT] = 0.300 vs. ΦST[NUC] = 0.013. Simulation studies indicated that the low levels of nuclear differentiation were not the result of limited power because of low levels of polymorphism. These findings, supported by palaeodistribution modelling and mismatch distribution analysis, are consistent with expansion of R. octopus from a single, limited refugium after the Last Glacial Maximum, followed by subsequent isolation, and that the discrepancy between the mitochondrial and nuclear markers is a result of the nuclear loci taking longer to reach mutation–drift equilibrium following the expansion as a result of their four-fold larger effective population size. The populations studied are probably not well connected via gene flow, and thus genetically as well as geographically distinct, although our findings also highlight the need to use a combination of organellar and nuclear markers to enable a more complete understanding of population demography and structure, particularly for species with large effective population sizes.

Phylogeographical analyses of shellfish viruses: inferring a geographical origin for ostreid herpesviruses OsHV-1 (Malacoherpesviridae)

Mortality episodes have regularly been affecting the shellfish industry throughout its history. Some of these mortalities, especially in the oyster industry, have been attributed to herpesviruses. Purification of viral particles and molecular characterization have led to the development of routine monitoring, as well as improved taxonomic classification. Ostreid herpesviruses (Malacoherpesviridae), mostly affecting Pacific oysters Crassostrea gigas, have been sporadically recorded in the French oyster industry since the early 1990s (OsHV-1 'reference'). From 2008, a new variant of ostreid herpesvirus (OsHV-1 mu Var) has emerged and seriously impacted oyster production in France and other European countries. Consequently, the presence of ostreid herpesviruses has been monitored in different oyster producing areas around the world. The present study compiles molecular data that are available from survey efforts and takes a biogeographical approach, in order to infer an origin for ostreid herpesviruses. The highest genotype diversity was found in East Asia, despite a lower survey effort in that area than in Europe. Genotype network analyses show that both populations of ostreid herpesviruses present in Europe (OsHV-1 'reference' and OsHV-1 mu Var) are closely related to genotypes recorded in Asia. Moreover, ostreid herpesviruses have been detected in wild and symptom-free populations of various Asian native Crassostrea species. In the rest of the world, ostreid herpesvirus genotypes were recorded from cultivated C. gigas, and mostly associated with mortality episodes. Results of this study are therefore highly suggestive of an Asian origin for these viruses, which can be pathogenic under farming conditions. It also highlights the risks of European stock improvements, by means of overseas shellfish imports.

Aspirin therapy in patients with acute respiratory distress syndrome (ARDS) is associated with reduced intensive care unit mortality: a prospective analysis

INTRODUCTION: Acute respiratory distress syndrome (ARDS) is a common clinical syndrome with high mortality and long-term morbidity. To date there is no effective pharmacological therapy. Aspirin therapy has recently been shown to reduce the risk of developing ARDS, but the effect of aspirin on established ARDS is unknown.

METHODS: In a single large regional medical and surgical ICU between December 2010 and July 2012, all patients with ARDS were prospectively identified and demographic, clinical, and laboratory variables were recorded retrospectively. Aspirin usage, both pre-hospital and during intensive care unit (ICU) stay, was included. The primary outcome was ICU mortality. We used univariate and multivariate logistic regression analyses to assess the impact of these variables on ICU mortality.

RESULTS: In total, 202 patients with ARDS were included; 56 (28%) of these received aspirin either pre-hospital, in the ICU, or both. Using multivariate logistic regression analysis, aspirin therapy, given either before or during hospital stay, was associated with a reduction in ICU mortality (odds ratio (OR) 0.38 (0.15 to 0.96) P = 0.04). Additional factors that predicted ICU mortality for patients with ARDS were vasopressor use (OR 2.09 (1.05 to 4.18) P = 0.04) and APACHE II score (OR 1.07 (1.02 to 1.13) P = 0.01). There was no effect upon ICU length of stay or hospital mortality.

CONCLUSION: Aspirin therapy was associated with a reduced risk of ICU mortality. These data are the first to demonstrate a potential protective role for aspirin in patients with ARDS. Clinical trials to evaluate the role of aspirin as a pharmacological intervention for ARDS are needed.

Bdellovibrio predation in the presence of decoys:Three-way bacterial interactions revealed by mathematical and experimental analyses

Bdellovibrio bacteriovorus is a small, gram-negative, motile bacterium that preys upon other gram-negative bacteria, including several known human pathogens. Its predation efficiency is usually studied in pure cultures containing solely B. bacteriovorus and a suitable prey. However, in natural environments, as well as in any possible biomedical uses as an antimicrobial, Bdellovibrio is predatory in the presence of diverse decoys, including live nonsusceptible bacteria, eukaryotic cells, and cell debris. Here we gathered and mathematically modeled data from three-member cultures containing predator, prey, and nonsusceptible bacterial decoys. Specifically, we studied the rate of predation of planktonic late-log-phase Escherichia coli S17-1 prey by B. bacteriovorus HD100, both in the presence and in the absence of Bacillus subtilis nonsporulating strain 671, which acted as a live bacterial decoy. Interestingly, we found that although addition of the live Bacillus decoy did decrease the rate of Bdellovibrio predation in liquid cultures, this addition also resulted in a partially compensatory enhancement of the availability of prey for predation. This effect resulted in a higher final yield of Bdellovibrio than would be predicted for a simple inert decoy. Our mathematical model accounts for both negative and positive effects of predator-prey-decoy interactions in the closed batch environment. In addition, it informs considerations for predator dosing in any future therapeutic applications and sheds some light on considerations for modeling the massively complex interactions of real mixed bacterial populations in nature.