Incorporating Financial Statement Information to Improve Forecasts of Corporate Taxable Income

We contribute to the research on the information content of earnings as it applies to the forecasting of economic activity across reporting models. We examine whether publicly available financial statement information is incrementally useful in forecasting confidentially reported taxable income. More precise firm-level taxable income forecasts can improve policymakers’ modeling of the tax system and their ability to analyze the effect of proposed changes in corporate tax law. When aggregated, improved micro-forecasts can also yield more accurate macro-forecasts of corporate taxable income, a significant component of the federal budget. We find that financial statement information improves firm-level estimates of future taxable income by providing more timely information. We also document the usefulness of the deferred tax valuation allowance in improving taxable income estimates for loss firms. Our evidence suggests public financial statement information complements proprietary data to improve estimates of future taxable income for budgetary and policy use

Middle and Late Pleistocene environmental history of the Marsworth area, south-central England

To elucidate the Middle and Late Pleistocene environmental history of south-central England, we report the stratigraphy, sedimentology, palaeoecology and geochronology of some deposits near the foot of the Chiltern Hills scarp at Marsworth, Buckinghamshire. The Marsworth site is important because its sedimentary sequences contain a rich record of warm stages and cold stages, and it lies close to the Anglian glacial limit. Critical to its history are the origin and age of a brown pebbly silty clay (diamicton) previously interpreted as weathered till. The deposits described infill a river channel incised into chalk bedrock. They comprise clayey, silty and gravelly sediments, many containing locally derived chalk and some with molluscan, ostracod and vertebrate remains. Most of the deposits are readily attributed to periglacial and fluvial processes, and some are dated by optically stimulated luminescence to Marine Isotope Stage (MIS) 6. Although our sedimentological data do not discriminate between a glacial or periglacial interpretation of the diamicton, amino-acid dating of three molluscan taxa from beneath it indicates that it is younger than MIS 9 and older than MIS 5e. This makes a glacial interpretation unlikely, and we interpret the diamicton as a periglacial slope deposit. The Pleistocene history reconstructed for Marsworth identifies four key elements: (1) Anglian glaciation during MIS 12 closely approached Marsworth, introducing far-travelled pebbles such as Rhaxella chert and possibly some fine sand minerals into the area. (2) Interglacial environments inferred from fluvial sediments during MIS 7 varied from fully interglacial conditions during sub-stages 7e and 7c, cool temperate conditions during sub-stage 7b or 7a, temperate conditions similar to those today in central England towards the end of the interglacial, and cool temperate conditions during sub-stage 7a. (3) Periglacial activity during MIS 6 involved thermal contraction cracking, permafrost development, fracturing of chalk bedrock, fluvial activity, slopewash, mass movement and deposition of loess and coversand. (4) Fully interglacial conditions during sub-stage 5e led to renewed fluvial activity, soil formation and acidic weathering

The Circadian Deadenylase Nocturnin Is Necessary for Stabilization of the iNOS mRNA in Mice

Nocturnin is a member of the CCR4 deadenylase family, and its expression is under circadian control with peak levels at night. Because it can remove poly(A) tails from mRNAs, it is presumed to play a role in post-transcriptional control of circadian gene expression, but its target mRNAs are not known. Here we demonstrate that Nocturnin expression is acutely induced by the endotoxin lipopolysaccharide (LPS). Mouse embryo fibroblasts (MEFs) lacking Nocturnin exhibit normal patterns of acute induction of TNFα and iNOS mRNAs during the first three hours following LPS treatment, but by 24 hours, while TNFα mRNA levels are indistinguishable from WT cells, iNOS message is significantly reduced 20-fold. Accordingly, analysis of the stability of the mRNAs showed that loss of Nocturnin causes a significant decrease in the half-life of the iNOS mRNA (t1/2 = 3.3 hours in Nocturnin knockout MEFs vs. 12.4 hours in wild type MEFs), while having no effect on the TNFα message. Furthermore, mice lacking Nocturnin lose the normal nighttime peak of hepatic iNOS mRNA, and have improved survival following LPS injection. These data suggest that Nocturnin has a novel stabilizing activity that plays an important role in the circadian response to inflammatory signals

The intra-tumoral stroma in patients with breast cancer increases with age

Purpose The tumor microenvironment in older patients is subject to changes. The tumor-stroma ratio (TSR) was evaluated in order to estimate the amount of intra-tumoral stroma and to evaluate the prognostic value of the TSR in older patients with breast cancer (≥70 years). Methods Two retrospective cohorts, the FOCUS study (N = 619) and the Nottingham Breast Cancer series (N = 1793), were used for assessment of the TSR on hematoxylin and eosin stained tissue slides. Results The intra-tumoral stroma increases with age in the FOCUS study and the Nottingham Breast Cancer series (B 0.031, 95% CI 0.006-0.057, P = 0.016 and B 0.034, 95% CI 0.015-0.054, P ≤ 0.001, respectively). Fifty-one percent of the patients from the Nottingham Breast Cancer series ≤40 years had a stroma-high tumor compared to 73% of the patients of ≥90 years from the FOCUS study. The TSR did not validate as an independent prognostic parameter in patients ≥70 years. Conclusions The intra-tumoral stroma increases with age. This might be the result of an activated tumor microenvironment. The TSR did not validate as an independent prognostic parameter in patients ≥70 years in contrast to young women with breast cancer as published previously

Mood and emotional reactivity of adolescents during the COVID-19 pandemic: the short-term and long-term effects and the impact of social and socioeconomic stressors

Adolescence is a formative period for socio-emotional development which is threatened by the COVID-19 pandemic. The current longitudinal study examined two aims: (1) the short- and long-term effects of the pandemic on young people’s mood (i.e. vigor, tension, and depression levels) and emotional reactivity (i.e. fluctuations in daily mood), and (2) the impact of stressors on mood, emotional reactivity, self-oriented (i.e. maladaptive behavior towards COVID-19 rules) and other-benefitting behaviors (i.e. behavior aimed at helping and comforting others). We conducted an online two-week daily diary study among 462 Dutch adolescents (Mage = 15.27 years, 64% females) and 371 young adults (Mage = 21.49 years, 81% females) in May 2020, with a follow-up in November 2020 (N = 238 and 231, respectively adolescents and young adults). In May 2020, young adults and older relative to younger adolescents showed higher levels and more fluctuations in tension and depression and lower levels of vigor. Vigor levels decreased and tension and depression levels increased between May 2020 and November 2020, especiall

Genetic Linkage and Association Analysis for Loneliness in Dutch Twin and Sibling Pairs Points to a Region on Chromosome 12q23–24

We obtained evidence from a large study in Dutch twins (N = 8387) and siblings (N = 2295) that variation in loneliness has a genetic component. The heritability estimate for loneliness, which was assessed as an ordinal trait, was 40% and did not differ between males and females. There were 682 sibling pairs with genotypic (around 400 microsatellite markers) data. We combined phenotypic and genotypic data to carry out a genome scan to localize QTLs for loneliness. One region on chromosome 12q23.3-24.3, showed near suggestive linkage. Genetic association tests within this region revealed significant association (p-value 0.009) with one of the alleles of marker D12S79 and with one of the alleles of neighbouring marker D12S395 (p-value 0.043). We review evidence for linkage in this region for psychiatric disorders and discuss our findings within this context. © 2006 Springer Science+Business Media, Inc

A Src-Tks5 Pathway Is Required for Neural Crest Cell Migration during Embryonic Development

In the adult organism, cell migration is required for physiological processes such as angiogenesis and immune surveillance, as well as pathological events such as tumor metastasis. The adaptor protein and Src substrate Tks5 is necessary for cancer cell migration through extracellular matrix in vitro and tumorigenicity in vivo. However, a role for Tks5 during embryonic development, where cell migration is essential, has not been examined. We used morpholinos to reduce Tks5 expression in zebrafish embryos, and observed developmental defects, most prominently in neural crest-derived tissues such as craniofacial structures and pigmentation. The Tks5 morphant phenotype was rescued by expression of mammalian Tks5, but not by a variant of Tks5 in which the Src phosphorylation sites have been mutated. We further evaluated the role of Tks5 in neural crest cells and neural crest-derived tissues and found that loss of Tks5 impaired their ventral migration. Inhibition of Src family kinases also led to abnormal ventral patterning of neural crest cells and their derivatives. We confirmed that these effects were likely to be cell autonomous by shRNA-mediated knockdown of Tks5 in a murine neural crest stem cell line. Tks5 was required for neural crest cell migration in vitro, and both Src and Tks5 were required for the formation of actin-rich structures with similarity to podosomes. Additionally, we observed that neural crest cells formed Src-Tks5-dependent cell protrusions in 3-D culture conditions and in vivo. These results reveal an important and novel role for the Src-Tks5 pathway in neural crest cell migration during embryonic development. Furthermore, our data suggests that this pathway regulates neural crest cell migration through the generation of actin-rich pro-migratory structures, implying that similar mechanisms are used to control cell migration during embryogenesis and cancer metastasis

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

GA4GH: International policies and standards for data sharing across genomic research and healthcare.

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe