Hybrid Tail Risk and Expected Stock Returns: When Does the Tail Wag the Dog?

This paper introduces a new, hybrid measure of covariance risk in the lower tail of the stock return distribution, motivated by the under-diversified portfolio holdings of individual investors, and investigates its performance in predicting the cross-sectional variation in stock returns over the sample period July 1963-December 2009. Our key innovation is that the covariance is measured across the states of the world in which the individual stock return is in its left tail, not across the corresponding tail states for the market return as in standard systematic risk measures. The results indicate a positive and significant relation between what we label hybrid tail covariance risk (H-TCR) and expected stock returns, in contrast to the insignificant or negative results for purely stock-specific or standard systematic tail risk measures. A trading strategy that goes long stocks in the highest H-TCR decile and shorts stocks in the lowest H-TCR decile produces average raw and risk-adjusted returns of 6% to 8% per annum, consistent with results from a cross-sectional regression analysis that controls for a battery of known predictors

Maxing Out: Stocks as Lotteries and the Cross-Section of Expected Returns

Motivated by existing evidence of a preference among investors for assets with lottery-like payoffs and that many investors are poorly diversified, we investigate the significance of extreme positive returns in the cross-sectional pricing of stocks. Portfolio-level analyses and firm-level cross-sectional regressions indicate a negative and significant relation between the maximum daily return over the past one month (MAX) and expected stock returns. Average raw and risk-adjusted return differences between stocks in the lowest and highest MAX deciles exceed 1% per month. These results are robust to controls for size, book-to-market, momentum, short-term reversals, liquidity, and skewness. Of particular interest, including MAX reverses the puzzling negative relation between returns and idiosyncratic volatility recently documented in Ang et al. (2006, 2008).

Site specific insertion of a transgene into the murine α-casein (CSN1S1) gene results in the predictable expression of a recombinant protein in milk

Gene loci of highly expressed genes provide ideal sites for transgene expression. Casein genes are highly expressed in mammals leading to the synthesis of substantial amounts of casein proteins in milk. We have assessed the α-casein (CSN1S1) gene as a site of transgene expression in transgenic mice and a mammary gland cell line. A transgene encoding an antibody light chain gene (A1L) was inserted into the α-casein gene using sequential homologous and site-specific recombination. Expression of the inserted transgene is directed by the α-casein promoter, is responsive to lactogenic hormone activation, leads to the synthesis of a chimeric α-casein/A1L transgene mRNA and secretion of the recombinant A1L protein into milk. Transgene expression is highly consistent in all transgenic lines, but lower than that of the α-casein gene (4%). Recombinant A1L protein accounted for 0.5% and 1.6% of total milk protein in heterozygous and homozygous transgenic mice, respectively. The absence of the α-casein protein in homozygous A1L transgenic mice leads to a reduction of total milk protein and delayed growth of the pups nursed by these mice. Overall, the data demonstrate that the insertion of a transgene into a highly expressed endogenous gene is insufficient to guarantee its abundant expression. This article is protected by copyright. All rights reserved.</p

Randomised controlled trial of early frenotomy in breastfed infants with mild-moderate tongue-tie

TRIAL DESIGN: A randomised, parallel group, pragmatic trial. SETTING: A large UK maternity hospital. PARTICIPANTS: Term infants <2 weeks old with a mild or moderate degree of tongue-tie, and their mothers who were having difficulties breastfeeding. OBJECTIVES: To determine if immediate frenotomy was better than standard breastfeeding support. INTERVENTIONS: Participants were randomised to an early frenotomy intervention group or a ‘standard care’ comparison group. OUTCOMES: Primary outcome was breastfeeding at 5 days, with secondary outcomes of breastfeeding self-efficacy and pain on feeding. Final assessment was at 8 weeks; 20 also had qualitative interviews. Researchers assessing outcomes, but not participants, were blinded to group assignment. RESULTS: 107 infants were randomised, 55 to the intervention group and 52 to the comparison group. Five-day outcome measures were available for 53 (96%) of the intervention group and 52 (100%) of the comparison group, and intention-to-treat analysis showed no difference in the primary outcome—Latch, Audible swallowing, nipple Type, Comfort, Hold score. Frenotomy did improve the tongue-tie and increased maternal breastfeeding self-efficacy. At 5 days, there was a 15.5% increase in bottle feeding in the comparison group compared with a 7.5% increase in the intervention group. After the 5-day clinic, 44 of the comparison group had requested a frenotomy; by 8 weeks only 6 (12%) were breastfeeding without a frenotomy. At 8 weeks, there were no differences between groups in the breastfeeding measures or in the infant weight. No adverse events were observed. CONCLUSIONS: Early frenotomy did not result in an objective improvement in breastfeeding but was associated with improved self-efficacy. The majority in the comparison arm opted for the intervention after 5 days

Reduced levels of two modifiers of epigenetic gene silencing, Dnmt3a and Trim28, cause increased phenotypic noise

Background: Inbred individuals reared in controlled environments display considerable variance in many complex traits but the underlying cause of this intangible variation has been an enigma. Here we show that two modifiers of epigenetic gene silencing play a critical role in the process.Results: Inbred mice heterozygous for a null mutation in DNA methyltransferase 3a (Dnmt3a) or tripartite motif protein 28 (Trim28) show greater coefficients of variance in body weight than their wild-type littermates. Trim28 mutants additionally develop metabolic syndrome and abnormal behavior with incomplete penetrance. Genome-wide gene expression analyses identified 284 significantly dysregulated genes in Trim28 heterozygote mutants compared to wild-type mice, with Mas1, which encodes a G-protein coupled receptor implicated in lipid metabolism, showing the greatest average change in expression (7.8-fold higher in mutants). This gene also showed highly variable expression between mutant individuals.Conclusions: These studies provide a molecular explanation of developmental noise in whole organisms and suggest that faithful epigenetic control of transcription is central to suppressing deleterious levels of phenotypic variation. These findings have broad implications for understanding the mechanisms underlying sporadic and complex disease in humans

Counter-Insurgency against ‘kith and kin’?: the British Army in Northern Ireland, 1970–76

This article argues that state violence in Northern Ireland during the period 1970–1976—when violence during the Troubles was at its height and before the re-introduction of the policy of police primacy in 1976—was on a greatly reduced scale from that seen in British counterinsurgency campaigns in the colonies after the Second World War. When the army attempted to introduce measures used in the colonies—curfews, internment without trial—these proved to be extremely damaging to London's political aims in Northern Ireland, namely the conciliation of the Catholic minority within the United Kingdom and the defeat of the IRA. However, the insistence by William Whitelaw, secretary of state for Northern Ireland (1972–73), on ‘throttling back'—the release of internees and the imposition of unprecedented restrictions on the use of violence by the army—put a serious strain on civil-military relations in Northern Ireland. The relatively stagnant nature of the conflict—with units taking casualties in the same small ‘patch’ of territory without opportunities for the types of ‘positive actions’ seen in the colonies—led to some deviancy on the part of small infantry units who sought informal, unsanctioned ways of taking revenge upon the local population. Meanwhile, a disbelieving and defensive attitude at senior levels of command in Northern Ireland meant that informal punitive actions against the local population were often not properly investigated during 1970–72, until more thorough civilian and military investigative procedures were put in place. Finally, a separation of ethnic and cultural identity between the soldiers and the local population—despite their being citizens of the same state—became professionally desirable in order for soldiers to carry out difficult, occasionally distasteful work

Efficient TALEN-mediated gene knockout in livestock

Transcription activator-like effector nucleases (TALENs) are programmable nucleases that join FokI endonuclease with the modular DNA-binding domain of TALEs. Although zinc-finger nucleases enable a variety of genome modifications, their application to genetic engineering of livestock has been slowed by technical limitations of embryo-injection, culture of primary cells, and difficulty in producing reliable reagents with a limited budget. In contrast, we found that TALENs could easily be manufactured and that over half (23/36, 64%) demonstrate high activity in primary cells. Cytoplasmic injections of TALEN mRNAs into livestock zygotes were capable of inducing gene KO in up to 75% of embryos analyzed, a portion of which harbored biallelic modification. We also developed a simple transposon coselection strategy for TALEN-mediated gene modification in primary fibroblasts that enabled both enrichment for modified cells and efficient isolation of modified colonies. Coselection after treatment with a single TALEN-pair enabled isolation of colonies with mono- and biallelic modification in up to 54% and 17% of colonies, respectively. Coselection after treatment with two TALEN-pairs directed against the same chromosome enabled the isolation of colonies harboring large chromosomal deletions and inversions (10% and 4% of colonies, respectively). TALEN-modified Ossabaw swine fetal fibroblasts were effective nuclear donors for cloning, resulting in the creation of miniature swine containing mono- and biallelic mutations of the LDL receptor gene as models of familial hypercholesterolemia. TALENs thus appear to represent a highly facile platform for the modification of livestock genomes for both biomedical and agricultural applications

Estimating population size, density and dynamics of Pre-Pottery Neolithic villages in the central and southern Levant: an analysis of Beidha, southern Jordan

The Pre-Pottery Neolithic (PPN) of the central and southern Levant played an integral role in the Neolithic Demographic Transition (NDT) from mobile hunter-gatherer to village-based, agro-pastoralist societies. An understanding of population dynamics is essential for reconstructing the trajectories of these early village societies. However, few investigations have produced absolute estimates of population parameters for these villages and those which have base estimates on a limited methodological framework. This research examines the methodological and theoretical basis for existing estimates, and explores a range of methodologies in order to derive more empirically-robust demographic data. Results reveal that commonly utilized methodologies and population density coefficients employed for estimating PPN village populations require re-evaluation. This article presents the application of methodologies to the PPNB site of Beidha in southern Jordan