On the Modelling and Forecasting of Multivariate Realized Volatility: Generalized Heterogeneous Autoregressive (GHAR) Model

Recent multivariate extensions of the popular heterogeneous autoregressive model (HAR) for realized volatility leave substantial information unmodelled in residuals. We propose to employ a system of seemingly unrelated regressions to model and forecast a realized covariance matrix to capture this information. We find that the newly proposed generalized heterogeneous autoregressive (GHAR) model outperforms competing approaches in terms of economic gains, providing better mean–variance trade‐off, while, in terms of statistical precision, GHAR is not substantially dominated by any other model. Our results provide a comprehensive comparison of the performance when realized covariance, subsampled realized covariance and multivariate realized kernel estimators are used. We study the contribution of the estimators across different sampling frequencies, and show that the multivariate realized kernel and subsampled realized covariance estimators deliver further gains compared to realized covariance estimated on a 5‐minute frequency. In order to show economic and statistical gains, a portfolio of various sizes is used. Copyright © 2016 John Wiley & Sons, Ltd.     

Mutations in the polyglutamine binding protein 1 gene cause X-linked mental retardation

We found mutations in the gene PQBP1 in 5 of 29 families with nonsyndromic (MRX) and syndromic (MRXS) forms of X-linked mental retardation (XLMR). Clinical features in affected males include mental retardation, microcephaly, short stature, spastic paraplegia and midline defects. PQBP1 has previously been implicated in the pathogenesis of polyglutamine expansion diseases. Our findings link this gene to XLMR and shed more light on the pathogenesis of this common disorder.     

Reweighting the general household survey 1979-2007

We have calculated two new sets of weights applicable to the General Household Survey (GHS) from 1979 to 2007. One of these is for use with any general analysis of GHS topics and the second is designed for analyses of data collected in the Family Information section. The methods used follow closely those employed by ONS from 1996 onwards. The performance of the weights is assessed in estimating the Total Fertility Rate (TFR) from 1971-2007, an aggregate measure of fertility for which reliable figures are available at national level from vital registration statistics. Our weights improve the GHS estimates, reducing bias both in the TFR and in age-specific fertility rates.     

Stability and change in fertility intentions in Britain, 1991-2007

The very low fertility experienced in several European countries in recent decades in the presence of higher intended family sizes has renewed interest in fertility intentions data. While the overall level of childbearing in Britain over the past few decades has remained relatively stable and high in comparison with many other European countries, we have seen sizeable increases in the age at which childbearing starts. This study uses data from the 1991 to 2007 General Household Surveys to examine trends in family intentions data in an attempt to arrive at a better understanding of these recent fertility developments. First, time trends in intended family size are compared with trends in observed fertility. Next, aggregate changes in intentions regarding the level and timing of fertility across the life course for cohorts are investigated together with the extent to which these aggregate intentions are matched by the subsequent childbearing of cohorts. Finally, both change across the life course and uncertainty in family intentions are examined. We conclude by discussing what these findings might tell us about contemporary reproductive decision making.     

On estimating contemporaneous quarterly regional GDP

Subnational regional jurisdictions rarely have at their disposal a reasonable array of timely statistics to monitor their economic condition. In light of this, we develop a procedure that simultaneously estimates a quarterly time series for all regions of a country based upon quarterly national and annual regional data. While other such techniques exist, we suggest a temporal error structure that eliminates possible spurious jumps. Using our approach, regional analysts should now be able to distribute national growth among regions as soon as quarterly national figures are released. In a Spanish application, we detail some practicalities of the process and show that our proposal produces better estimates than the uniregional methods often used. Copyright © 2007 John Wiley & Sons. Ltd.     

The occurrence of facultative paedomorphosis in a lacustrine population of the Pyrenean newt (Calotriton asper): morphology and age structure

Facultative paedomorphosis is a common polyphenism in newts where two alternative phenotypes can coexist: metamorphs and paedomorphs (mature with larval traits, i.e. retaining gills). This phenomenon has been reported in some lacustrine populations of the Pyrenean newt (Calotriton asper). The morphology and life-history traits were studied in a lacustrine population of this species with the occurrence of facultative paedomorphosis. The results showed that 24.3% of adults retained gills at different levels of reabsorption and had a smoother skin compared with the other populations, which were fully metamorphic. The body size and shape showed significant sexual differences, with males being larger than females. The presence of paedomorphic traits also affected the body size and shape, revealing a complex pattern of growth in which metamorphic adults were larger than paedomorphs. The age structure was different between sexes, with a median age of 10.5 and 7 years and longevity of 19 and 14 years in males and females, respectively. Considering each sex separately, the age structure was not significantly different between metamorphic and paedomorphic newts. In addition, metamorphosed and branchiate juveniles were found with a maximum age of 13 and 20 years, respectively. Remarkably, long-lived larvae with an exceptional individual of 18 years were found, which has not previously been reported in any other newt species. The mechanisms that can explain the evolution of paedomorphosis are complex and comprise the interaction of multiple factors related to the cost of reproduction and growth.     

Simvastatin overcomes the resistance to serum withdrawal-induced apoptosis of lymphocytes from Alzheimer’s disease patients

Statins may exert beneficial effects on Alzheimer’s disease (AD) patients. Based on the antineoplastic and apoptotic effects of statins in a number of cell types, we hypothesized that statins may be able to protect neurons by controlling the regulation of cell cycle and/or apoptosis. A growing body of evidence indicates that neurodegeneration involves the cell-cycle activation in postmitotic neurons. Failure of cell-cycle control is not restricted to neurons in AD patients, but occurs in peripheral cells as well. For these reasons, we studied the role of simvastatin (SIM) on cell survival/death in lymphoblasts from AD patients. We report here that SIM induces apoptosis in AD lymphoblasts deprived of serum. SIM interacts with PI3K/Akt and ERK1/2 signaling pathways thereby decreasing the serum withdrawal-enhanced levels of the CDK inhibitor p21^Cip1 (p21) and restoring the vulnerability of AD cells to trophic factor deprivation.     

Molecular recycling within amyloid fibrils

Amyloid fibrils are thread-like protein aggregates with a core region formed from repetitive arrays of beta-sheets oriented parallel to the fibril axis. Such structures were first recognized in clinical disorders, but more recently have also been linked to a variety of non-pathogenic phenomena ranging from the transfer of genetic information to synaptic changes associated with memory. The observation that many proteins can convert into similar structures in vitro has suggested that this ability is a generic feature of polypeptide chains. Here we have probed the nature of the amyloid structure by monitoring hydrogen/deuterium exchange in fibrils formed from an SH3 domain using a combination of nuclear magnetic resonance spectroscopy and electrospray ionization mass spectrometry. The results reveal that under the conditions used in this study, exchange is dominated by a mechanism of dissociation and re-association that results in the recycling of molecules within the fibril population. This insight into the dynamic nature of amyloid fibrils, and the ability to determine the parameters that define this behaviour, have important implications for the design of therapeutic strategies directed against amyloid disease.     

Endonuclease G is a novel determinant of cardiac hypertrophy and mitochondrial function

Left ventricular mass (LVM) is a highly heritable trait and an independent risk factor for all-cause mortality. So far, genome-wide association studies have not identified the genetic factors that underlie LVM variation, and the regulatory mechanisms for blood-pressure-independent cardiac hypertrophy remain poorly understood. Unbiased systems genetics approaches in the rat now provide a powerful complementary tool to genome-wide association studies, and we applied integrative genomics to dissect a highly replicated, blood-pressure-independent LVM locus on rat chromosome 3p. Here we identified endonuclease G (Endog), which previously was implicated in apoptosis but not hypertrophy, as the gene at the locus, and we found a loss-of-function mutation in Endog that is associated with increased LVM and impaired cardiac function. Inhibition of Endog in cultured cardiomyocytes resulted in an increase in cell size and hypertrophic biomarkers in the absence of pro-hypertrophic stimulation. Genome-wide network analysis unexpectedly implicated ENDOG in fundamental mitochondrial processes that are unrelated to apoptosis. We showed direct regulation of ENDOG by ERR-α and PGC1α (which are master regulators of mitochondrial and cardiac function), interaction of ENDOG with the mitochondrial genome and ENDOG-mediated regulation of mitochondrial mass. At baseline, the Endog-deleted mouse heart had depleted mitochondria, mitochondrial dysfunction and elevated levels of reactive oxygen species, which were associated with enlarged and steatotic cardiomyocytes. Our study has further established the link between mitochondrial dysfunction, reactive oxygen species and heart disease and has uncovered a role for Endog in maladaptive cardiac hypertrophy.