Fetal growth restriction results in remodeled and less efficient hearts in children

Background— Fetal growth restriction (FGR) affects 5% to 10% of newborns and is associated with increased cardiovascular mortality in adulthood. The most commonly accepted hypothesis is that fetal metabolic programming leads secondarily to diseases associated with cardiovascular disease, such as obesity, diabetes mellitus, and hypertension. Our main objective was to evaluate the alternative hypothesis that FGR induces primary cardiac changes that persist into childhood. Methods and Results— Within a cohort of fetuses with growth restriction identified in fetal life and followed up into childhood, we randomly selected 80 subjects with FGR and compared them with 120 normally grown fetuses, matched for gender, birth date, and gestational age at birth. Cardiovascular assessment was performed in childhood (mean age of 5 years). Compared with control subjects, children with FGR had a different cardiac shape, with increased transversal diameters and more globular cardiac ventricles. Although left ejection fraction was similar among the study groups, stroke volume was reduced significantly, which was compensated for by an increased heart rate to maintain output in severe FGR. This was associated with subclinical longitudinal systolic dysfunction (decreased myocardial peak velocities) and diastolic changes (increased E/E' ratio and E deceleration time). Children with FGR also had higher blood pressure and increased intima-media thickness. For all parameters evaluated, there was a linear increase with the severity of growth restriction. Conclusions— These findings suggest that FGR induces primary cardiac and vascular changes that could explain the increased predisposition to cardiovascular disease in adult life. If these results are confirmed, the impact of strategies with beneficial effects on cardiac remodeling should be explored in children with FGR.

Joint purchasers and the presumption of joint beneficial ownership:a matter of informed choice?

This paper examines the ruling of Jones v Kernott and shows the results of an empirical survey of conveyancing solicitors and their practices where so affected by the ruling. In particular the paper considers how conveyancing practitioners deal with the issue of organising trusts of land and giving advice to clients in relation to the co-purchase of land.

A critical analysis of the 'amyloid cascade hypothesis'

The 'amyloid cascade hypothesis' (ACH) is the most influential model of the pathogenesis of Alzheimer's disease (AD). The hypothesis proposes that the deposition of β-amyloid (Aβ) is the initial pathological event in AD, leading to the formation of extracellular senile plaques (SP), tau-immunoreactive neurofibrillary tangles (NFT), neuronal loss, and ultimately, clinical dementia. Ever since the formulation of the ACH, however, there have been questions regarding whether it completely describes AD pathogenesis. This review critically examines various aspects of the ACH including its origin and development, the role of amyloid precursor protein (APP), whether SP and NFT are related to the development of clinical dementia, whether Aβ and tau are 'reactive' proteins, and whether there is a pathogenic relationship between SP and NFT. The results of transgenic experiments and treatments for AD designed on the basis of the ACH are also reviewed. It was concluded: (1) Aβ and tau could be the products rather than the cause of neuro-degeneration in AD, (2) it is doubtful whether there is a direct causal link between Aβ and tau, and (3) SP and NFT may not be directly related to the development of dementia, (4) transgenic models involving APP alone do not completely replicate AD pathology, and (5) treatments based on the ACH have been unsuccessful. Hence, a modification of the ACH is proposed which may provide a more complete explanation of the pathogenesis of AD.

On Statistical Hypothesis Testing via Simulation Method

A procedure for calculating critical level and power of likelihood ratio test, based on a Monte-Carlo simulation method is proposed. General principles of software building for its realization are given. Some examples of its application are shown.

Riemann's Hypothesis

Riemann’s memoir is devoted to the function π(x) defined as the number of prime numbers less or equal to the real and positive number x. This is really the fact, but the “main role” in it is played by the already mentioned zeta-function.

Is more capability always beneficial for firm performance? Market orientation, core business process capabilities, and business environment

This study examines the role of capabilities in core marketing-related business processes–product development management (PDM), supply chain management (SCM) and customer relationship management (CRM)–in translating a firm’s market orientation (MO) into firm performance. The study is the first to examine the interplay of all three business process capabilities simultaneously, while investigating how environmental conditions moderate their performance effects. A moderated mediation analysis of 468 product-focused firms finds that PDM and CRM process capabilities play important mediating roles, whereas SCM process capability does not mediate the relationship between MO and performance. However, the relative importance of the capabilities as mediators varies along the degree of environmental turbulence, and under certain conditions, an increase in the level of business process capability may even turn detrimental.

Specificity, stability and comparative physiology of coral-Symbiodinium mutualisms: Evaluating the potential for acclimation and/or adaptation in reef corals

The relationship between reef corals and endosymbiotic dinoflagellates is fundamental to the existence of coral reefs. To evaluate the fidelity of coral-Symbiodinium mutualisms, corals maintained in aquaria for years were analyzed by denaturant gradient gel electrophoresis (DGGE). Comparing Symbiodinium populations of captive aquarium colonies with known associations in nature is a practical way of examining partner flexibility. The finding of "normal" symbiont populations in corals existing under highly variable conditions supports the premise that most coral colonies possess stable associations. High sensitivity real-time PCR (rtPCR) was used to evaluate background populations of the putatively stress-tolerant Symbiodinium D in reef corals of the Caribbean. Analyses of samples collected during periods of environmental stability indicate the ability of Symbiodinium D to associate with a wider diversity of host taxa than previously recognized. To gain a broader perspective with regard to the ecology of Symbiodinium D1a, rtPCR and DGGE were used to evaluate the symbiont populations of reef corals from Barbados before and after the 2005 mass coral bleaching. Background populations were observed in 56% of the host genera prior to observations of bleaching. These findings indicate that 'stress', not 'bleaching', caused the displacement of 'natural' symbiont population and the opportunistic proliferation of D1a in many host taxa. Of the 12 host taxa monitored before and after the bleaching event, there was a 40% increase in colonies hosting Symbiodinium D1a. Together, these studies elucidate the mechanism responsible for recent observations reporting the emergence of Symbiodinium D following thermal disturbances. These observations are now most easily explained as the disproportionate growth of existing in hospite symbiont populations, rather than novel symbiont acquisition subsequent to bleaching. To evaluate the comparative "fitness" of corals able to host multiple symbiont types, rates of calcification were measured in P. verrucosa hosting either Symbiodinium C1b-c or D1 at elevated temperature. Rates of calcification decreased significantly for both host-symbiont combinations, but differences attributable to symbiont composition were not detected. This research improves our knowledge of the symbiosis biology and ecology of reef corals and contributes information necessary to most accurately predict the response of these ecosystems to global climate changes.

Contribution of the vasculature to the Alzheimer's disease process

One of the pathological hallmarks of Alzheimer's disease (AD) brain is extracellular β-amyloid (Aβ) plaques containing 39-42 amino acid Aβ peptides. The deposition of Aβ around blood vessels, known as Cerebral amyloid angiopathy (CAA), is also a common feature in AD brain. Vascular density and cerebral blood flow are reduced in AD brains, and vascular risk factors such as hypertension and diabetes are also risk factors for AD. We have shown previously that Aβ peptides can potently inhibit angiogenesis both in-vitro and in-vivo, but the mechanism of action for this effect is not known. Therefore, my first hypothesis was that particular amino acid sequence(s) within the Aβ peptide are required for inhibition of angiogenesis. From this aim, I found a peptide sequence which was critical for anti-angiogenic activity (HHQKLVFF). This sequence contains a heparan sulfate proteoglycan growth factor binding domain implying that Aβ can interfere with growth factor signaling. Leading on from this, my second hypothesis was that Aβ can inhibit angiogenesis by binding to growth factor receptors. I found that Aβ can bind to Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2), and showed that this is one mechanism by which Aβ can inhibit angiogenesis. Since the vasculature is disrupted in AD brains, I investigated whether a strategy to increase brain vascularization would be beneficial against AD pathology. Therefore, my third hypothesis was that voluntary exercise (which is known to increase brain vascularization in rodents) can ameliorate Aβ pathology, increase brain vascularization, and improve behavioral deficits in a transgenic mouse model of AD. I found that exercise has no effect on Aβ pathology, brain vascularization or behavioral deficits. Therefore, in the transgenic mouse model that I used, exercise is an ineffective therapeutic strategy against AD pathology and symptoms.

Tests of the Intersensory Redundancy Hypothesis across early postnatal development

The Intersensory Redundancy Hypothesis (IRH; Bahrick & Lickliter, 2000, 2002, 2012) predicts that early in development information presented to a single sense modality will selectively recruit attention to modality-specific properties of stimulation and facilitate learning of those properties at the expense of amodal properties (unimodal facilitation). Vaillant (2010) demonstrated that bobwhite quail chicks prenatally exposed to a maternal call alone (unimodal stimulation) are able to detect a pitch change, a modality-specific property, in subsequent postnatal testing between the familiarized call and the same call with altered pitch. In contrast, chicks prenatally exposed to a maternal call paired with a temporally synchronous light (redundant audiovisual stimulation) were unable to detect a pitch change. According to the IRH (Bahrick & Lickliter, 2012), as development proceeds and the individual's perceptual abilities increase, the individual should detect modality-specific properties in both nonredundant, unimodal and redundant, bimodal conditions. However, when the perceiver is presented with a difficult task, relative to their level of expertise, unimodal facilitation should become evident. The first experiment of the present study exposed bobwhite quail chicks 24 hr after hatching to unimodal auditory, nonredundant audiovisual, or redundant audiovisual presentations of a maternal call for 10min/hr for 24 hours. All chicks were subsequently tested 24 hr after the completion of the stimulation (72 hr following hatching) between the familiarized maternal call and the same call with altered pitch. Chicks from all experimental groups (unimodal, nonredundant audiovisual, and redundant audiovisual exposure) significantly preferred the familiarized call over the pitch-modified call. The second experiment exposed chicks to the same exposure conditions, but created a more difficult task by narrowing the pitch range between the two maternal calls with which they were tested. Chicks in the unimodal and nonredundant audiovisual conditions demonstrated detection of the pitch change, whereas the redundant audiovisual exposure group did not show detection of the pitch change, providing evidence of unimodal facilitation. These results are consistent with predictions of the IRH and provide further support for the effects of unimodal facilitation and the role of task difficulty across early development.

Evidence of the heterogeneous market hypothesis using wavelet multi -resolution analysis

In finance literature many economic theories and models have been proposed to explain and estimate the relationship between risk and return. Assuming risk averseness and rational behavior on part of the investor, the models are developed which are supposed to help in forming efficient portfolios that either maximize (minimize) the expected rate of return (risk) for a given level of risk (rates of return). One of the most used models to form these efficient portfolios is the Sharpe's Capital Asset Pricing Model (CAPM). In the development of this model it is assumed that the investors have homogeneous expectations about the future probability distribution of the rates of return. That is, every investor assumes the same values of the parameters of the probability distribution. Likewise financial volatility homogeneity is commonly assumed, where volatility is taken as investment risk which is usually measured by the variance of the rates of return. Typically the square root of the variance is used to define financial volatility, furthermore it is also often assumed that the data generating process is made of independent and identically distributed random variables. This again implies that financial volatility is measured from homogeneous time series with stationary parameters. In this dissertation, we investigate the assumptions of homogeneity of market agents and provide evidence for the case of heterogeneity in market participants' information, objectives, and expectations about the parameters of the probability distribution of prices as given by the differences in the empirical distributions corresponding to different time scales, which in this study are associated with different classes of investors, as well as demonstrate that statistical properties of the underlying data generating processes including the volatility in the rates of return are quite heterogeneous. In other words, we provide empirical evidence against the traditional views about homogeneity using non-parametric wavelet analysis on trading data, The results show heterogeneity of financial volatility at different time scales, and time-scale is one of the most important aspects in which trading behavior differs. In fact we conclude that heterogeneity as posited by the Heterogeneous Markets Hypothesis is the norm and not the exception.

Development of the Sphere Overlap Scale (SOS) : compartmentalization and the spillover hypothesis

The purpose of this study was to create a scale that could measure compartmentalization. In the first of two studies 311 working undergraduates were asked to indicate agreement with 119 items that measured compartmentalization. The resulting scale's reliability and validity were evaluated by having a second sample of 312 working students complete the items that comprise a sphere overlap scale, two measures of spillover, and a measure of personality, coping, and demoralization. Although the study's original goal was not realized, its procedures were successful in developing a short (10-item) measure of work-to-home spillover whose items loaded on a single factor. Structural equation modeling indicated that SOS items were correlated with existing measures of spillover and could be discriminated from related concepts of personality and coping. The SOS was also more highly correlated with demoralization than existing measures of spillover in hierarchical analyses that controlled for demographic factors, personality characteristics, and coping style. It is concluded that the SOS shows enough promise to warrant the cost of its appraisal as an alternative measure of spillover in a longitudinal study.

Data compilation on the biological response to ocean acidification: environmental and experimental context of data sets and related literature

The exponential growth of studies on the biological response to ocean acidification over the last few decades has generated a large amount of data. To facilitate data comparison, a data compilation hosted at the data publisher PANGAEA was initiated in 2008 and is updated on a regular basis (doi:10.1594/PANGAEA.149999). By January 2015, a total of 581 data sets (over 4 000 000 data points) from 539 papers had been archived. Here we present the developments of this data compilation five years since its first description by Nisumaa et al. (2010). Most of study sites from which data archived are still in the Northern Hemisphere and the number of archived data from studies from the Southern Hemisphere and polar oceans are still relatively low. Data from 60 studies that investigated the response of a mix of organisms or natural communities were all added after 2010, indicating a welcomed shift from the study of individual organisms to communities and ecosystems. The initial imbalance of considerably more data archived on calcification and primary production than on other processes has improved. There is also a clear tendency towards more data archived from multifactorial studies after 2010. For easier and more effective access to ocean acidification data, the ocean acidification community is strongly encouraged to contribute to the data archiving effort, and help develop standard vocabularies describing the variables and define best practices for archiving ocean acidification data.

Joint hypothesis tests for multidimensional inequality indices

Acknowledgments This work has been undertaken with the support of the A*MIDEX project (n ∘ ANR-11-IDEX-0001-02) funded by the “Investissements d’Avenir” French Government program, managed by the French National Research Agency (ANR). We are grateful to Julian Williams, Editor Badi H. Baltagi and an anonymous referee for helpful comments. We are responsible for any errors.

A molecular analysis of the interactions of escherichia coli and macrophages

Escherichia coli (E.coli) is a diverse bacterial species that primarily forms a beneficial symbiotic relationship with the host in the human lower gastrointestinal track (GIT), however it can also be pathogenic in this environment. Furthermore, some strains can diverge from the GIT and occupy niches such as the urinary tract. In all these environments, E. coli interacts with the immune system and macrophages represent the front line of the innate immune system. In this study we characterise the immune response by macrophages to E. coli infection. It was shown that E. coli broadly provoke a similar cytokine response during macrophages infection and furthermore are degraded primarily by the phagocytosis pathway. Recently a new group of E. coli called Adherent Invasive Escherichia coli (AIEC) has been described. AIEC are present in the guts of Crohn’s disease (CD) patients at a higher frequency than in healthy patients. AIEC can replicate in macrophages but the mechanism for this is not fully understood. The processing of AIEC by macrophages was investigated and it was shown that AIEC only replicated in permissive macrophages. Furthermore, even in a permissive macrophages AIEC are trafficked through macrophages in a similar manner to commensal E. coli. This supports the hypothesis that AIEC are highly similar to commensal E. coli and only cause pathogenicity when present in the permissive environment of the gut of CD patients. Replication in macrophages requires functioning metabolic pathways and it was identified that glycolysis is important for AIEC survival in macrophages. AIEC mutants without a fully functioning glycolysis pathway induced less IL-1β cytokine release from macrophages than wild type strain suggesting that metabolism plays a role in inflammasome activation. Furthermore, AIEC mutants that could not produce the glycolytic end product acetate induced significantly reduced IL-1β release during infection. This suggest that the acetate molecule or a phenotypic effect of its production may be a driver of IL-1β release from AIEC infected macrophages. The interaction of uropathogenic E. coli (UPEC) with macrophages was also investigated. UPEC induced very high levels of cytotoxicity in human macrophages which was shown to be dependent on the production of the pore forming toxin α-hemolysin. However, UPEC did not induced high levels of cytotoxicity in murine macrophages suggesting there are species specific sensitivity to α-hemolysin that should be considered when studying UPEC pathogenicity in murine models.