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This paper derives an optimal timing strategy for a regular slow trader considering investing in a high-frequency trading (HFT) technology. The market is fragmented, and slow traders compete with fast traders for trade execution. Given this optimal timing rule, I then char- acterise the equilibrium level of fast trading in the market as well as the welfare-maximising socially optimal level. I show that there is always a unique cost of investment such that the equilibrium level of fast trading and the socially optimal level coincide. Finally I discuss potential policy responses to addressing equilibrium and social optimality misalignment in HFT.

Despite the considerable reductions in primary and secondary air pollutants in China, surface ozone levels have increased in recent years. We report a trend of 3.3 ± 4.7 μg.m−3 year−1 in the annual mean maximum daily average ozone over an 8-h period (MDA8 ozone) across China between 2015 and 2019. Leveraging the Kolmogorov–Zurbenko filter method, we find that meteorology enhanced the ozone levels in Beijing–Tianjin–Hebei (BTH), the Yangtze River Delta (YRD), and the Pearl River Delta (PRD) while the reduction of solar radiation and the planetary boundary layer height accelerated ozone decreases in the Sichuan Basin (SCB) after 2017. Solar radiation and temperature increases, together with the reduction in sea level pressure, were the main contributors to enhance ozone in the YRD. They also contributed to 32% of ozone increases in BTH. Weaker meridional wind, lower relative humidity, and higher temperature escalated ozone enhancement in the PRD between 2016 and 2018. Regarding precursor emissions, NO2 long-term components showed a noticeable decline in all regions after 2017, partially due to the introduction of the most current action plan to reduce air pollutants over China in 2018. In contrast, the satellite-retrieved data suggest that VOC concentrations did not change substantially in target regions during the study period. After 2017, however, VOCs slightly increased in BTH, the YRD, and the PRD, which might be driven by temperature enhancements. Overall, the impact of meteorology on ozone variations was dominant in the YRD, the PRD, and the SCB from 2015 to 2019. Precursor emissions, however, played a leading role in ozone enhancement over the BTH. We also found that BTH and the YRD were in a transitional ozone formation regime while the PRD and the SCB tended to be more NOx-sensitive.

Microbial communities have considerable impacts on animal health. However, only in recent years have the host factors impacting microbiome composition been explored. An increasing wealth of microbiome data in combination with decades of research on behavior, physiology, and development have resulted in the European honey bee (Apis mellifera) as a burgeoning model system for studying the influence of host behavior on the microbiota. Honey bees are eusocial insects which exhibit striking behavioral and physiological differences between castes and life stages. These include changes in social contact, environmental exposure, diet, and physiology: all factors which can affect microbial composition and function. The honey bee system offers an opportunity to tease apart the interactive effects of all these factors on microbiota composition, abundance, and diversity.

Background Stillbirth rates in the United Kingdom (UK) are amongst the highest of all developed nations. The association between small-for-gestational-age (SGA) foetuses and stillbirth is well established, and observational studies suggest that improved antenatal detection of SGA babies may halve the stillbirth rate. The Growth Assessment Protocol (GAP) describes a complex intervention that includes risk assessment for SGA and screening using customised fundal-height growth charts. Increased detection of SGA from the use of GAP has been implicated in the reduction of stillbirth rates by 22%, in observational studies of UK regions where GAP uptake was high. This study will be the first randomised controlled trial examining the clinical efficacy, health economics and implementation of the GAP programme in the antenatal detection of SGA. Methods/design In this randomised controlled trial, clusters comprising a maternity unit (or National Health Service Trust) were randomised to either implementation of the GAP programme, or standard care. The primary outcome is the rate of antenatal ultrasound detection of SGA in infants found to be SGA at birth by both population and customised standards, as this is recognised as being the group with highest risk for perinatal morbidity and mortality. Secondary outcomes include antenatal detection of SGA by population centiles, antenatal detection of SGA by customised centiles, short-term maternal and neonatal outcomes, resource use and economic consequences, and a process evaluation of GAP implementation. Qualitative interviews will be performed to assess facilitators and barriers to implementation of GAP. Discussion This study will be the first to provide data and outcomes from a randomised controlled trial investigating the potential difference between the GAP programme compared to standard care for antenatal ultrasound detection of SGA infants. Accurate information on the performance and service provision requirements of the GAP protocol has the potential to inform national policy decisions on methods to reduce the rate of stillbirth. Trial registration Primary registry and trial identifying number: ISRCTN 67698474. Registered on 2 November 2016. Electronic supplementary material The online version of this article (10.1186/s13063-019-3242-6) contains supplementary material, which is available to authorized users.

Photoreceptor loss is the final common endpoint in most retinopathies that lead to irreversible blindness, and there are no effective treatments to restore vision1,2. Chemical reprogramming of fibroblasts offers an opportunity to reverse vision loss; however, the generation of sensory neuronal subtypes such as photoreceptors remains a challenge. Here we report that the administration of a set of five small molecules can chemically induce the transformation of fibroblasts into rod photoreceptor-like cells. The transplantation of these chemically induced photoreceptor-like cells (CiPCs) into the subretinal space of rod degeneration mice (homozygous for rd1, also known as Pde6b) leads to partial restoration of the pupil reflex and visual function. We show that mitonuclear communication is a key determining factor for the reprogramming of fibroblasts into CiPCs. Specifically, treatment with these five compounds leads to the translocation of AXIN2 to the mitochondria, which results in the production of reactive oxygen species, the activation of NF-κB and the upregulation of Ascl1. We anticipate that CiPCs could have therapeutic potential for restoring vision. A set of five small molecules can induce the transformation of fibroblasts into rod photoreceptor-like cells, which can partially restore pupil reflex and visual function when transplanted into a rod degeneration mouse model.

Iceberg orders, which allow traders to hide a portion of their order size, have become prevalent in many electronic limit order markets. This paper investigates, via a real options analysis, whether small traders, who have no use for submitting iceberg orders, are better off submitting their orders to fully transparent markets which have low depth, or to more liquid markets which do permit the placement of iceberg orders by large traders. Surprisingly, we find that in the context of our model, small traders are better off submitting to fully transparent markets in spite of them being less liquid.

The thermal sensitivities of organisms regulate a wide range of ecological interactions, including host-parasite dynamics. The effect of temperature on disease ecology can be remarkably complex in disease systems where the hosts are ectothermic and where thermal conditions constrain pathogen reproductive rates. Amphibian chytridiomycosis, caused by the pathogen Batrachochytrium dendrobatidis (Bd), is a lethal fungal disease that is influenced by temperature. However, recent temperature studies have produced contradictory findings, suggesting that our current understanding of thermal effects on Bd may be incomplete. We investigated how temperature affects three different Bd strains to evaluate diversity in thermal responses. We quantified growth across the entire thermal range of Bd, and beyond the known thermal limits (T-max and T-min). Our results show that all Bd strains remained viable and grew following 24 h freeze (-12 degrees C) and heat shock (28 degrees C) treatments. Additionally, we found that two Bd strains had higher logistic growth rates (r) and carrying capacities (K) at the upper and lower extremities of the temperature range, and especially in low temperature conditions (2-3 degrees C). In contrast, a third strain exhibited relatively lower growth rates and carrying capacities at these same thermal extremes. Overall, our results suggest that there is considerable variation among Bd strains in thermal tolerance, and they establish a new thermal sensitivity profile for Bd. More generally, our findings point toward important questions concerning the mechanisms that dictate fungal thermal tolerances and temperature-dependent pathogenesis in other fungal disease systems. National Science Foundation [IOS-13542421]; Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health [P20GM103451] We thank Gabriela Rios-Sotelo, Rachel Perez, Cecelia Ogunro and Zachary Gajewski for their assistance with data collection and editing. This study was supported by the National Science Foundation (IOS-13542421 to EBR and JV) and an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health (P20GM103451 to JV).

This paper derives an optimal timing strategy for a regular slow trader considering investing in a high-frequency trading technology. The market is fragmented, and slow traders compete with fast traders for trade execution. Assuming all traders adhere to the optimal strategy derived for a single trader, I then determine the equilibrium level of fast trading in the market across all traders, as well as the socially optimal level. I show that there is a unique level of market fragmentation such that the equilibrium level of fast trading and the socially optimal level coincide. Moreover, the real options approach to investment yields an equilibrium level which is less socially optimal than the equilibrium level obtained via the classical net present value approach.

Minor changes (~0.1 m/s) in human gait speed are predictive of various measures of decline and can be used to identify at-risk individuals prior to further decline. These associations are possible due to an abundance of human clinical research. However, age-related gait changes are not well defined in rodents, even though rodents are used as the primary pre-clinical model for many disease states as well as aging research. Our study investigated the usefulness of a novel automated system, the CatWalk™ XT, to measure age-related differences in gait. Furthermore, age-related functional declines have been associated with decreases in the reduced to oxidized glutathione ratio leading to a pro-oxidizing cellular shift. Therefore the secondary aim of this study was to determine whether chronic glutathione deficiency led to exacerbated age-associated impairments. Groups of male and female wild-type (gclm+/+) and knock-out (gclm-/-) mice aged 4, 10 and 17 months were tested on the CatWalk and gait measurements recorded. Similar age-related declines in all measures of gait were observed in both males and females, and chronic glutathione depletion was associated with some delays in age-related declines, which were further exacerbated. In conclusion, the CatWalk is a useful tool to assess gait changes with age, and further studies will be required to identify the potential compensating mechanisms underlying the effects observed with the chronic glutathione depletion.

The link between income and subjective satisfaction with one’s financial situation is explored in this paper using a panel analysis of 1,998 individuals tracked through the course of the boom period in Ireland, 1994-2001. A dynamic ordered probit model which incorporates state dependence and controls for correlated individual effects and the initial conditions problem is applied. The impact of the level of household income, the time-path of income and deviations of individual income from reference group income and household income are all considered. To the extent that income influences financial satisfaction, there is strong evidence from this paper that the level of household income has the most important effect but this effect is lessened once persistence in the data is controlled for and is diminishing at higher income levels. Controlling for income and socio-economic characteristics, the positive deviations of household income from reference group income are found to have a positive effect on financial satisfaction as are positive deviations of individual income from household income.

This paper outlines a real options approach to valuing those announcements which are made by firms outside of their legal requirements. From the firm's perspective, information is disclosed only if the manager of the firm is sufficiently certain that the market response to the announcement will have a positive impact on the value of the firm.\ud \ud When debt financing is possible we find that the manager adopts a more transparent disclosure policy, thus violating the Modigliani-Miller theorem on irrelevance of capital structure.

Comparing self-assessed indicators of subjective outcomes such as health, work disability, political efficacy, job satisfaction, etc. across countries or socio-economic groups is often hampered by the fact that different groups use systematically different response scales. Anchoring vignettes have been introduced as an effective tool to correct for such differences. This paper develops an integrated framework in which objective measurements are used to validate the vignette based corrections. The framework is applied to vignettes and objective and subjective self-assessments of drinking behavior by students in Ireland. Model comparisons using the Akaike information criterion favor a specification with response consistency and vignette corrected response scales. Put differently, vignette based corrections appear quite effective in bringing objective and subjective measures closer together. Diageo Ireland PLC ; Higher Education Authority Programme for Research in Third-Level Institutions (PRTLI) ; NIA

Homologous recombination in ES cells was employed to generate mice with targeted deletion of the first three exons of the γ-synuclein gene. Complete inactivation of gene expression in null mutant mice was confirmed on the mRNA and protein levels. Null mutant mice are viable, are fertile, and do not display evident phenotypical abnormalities. The effects of γ-synuclein deficiency on motor and peripheral sensory neurons were studied by various methods in vivo and in vitro. These two types of neurons were selected because they both express high levels of γ-synuclein from the early stages of mouse embryonic development but later in the development they display different patterns of intracellular compartmentalization of the protein. We found no difference in the number of neurons between wild-type and null mutant animals in several brain stem motor nuclei, in lumbar dorsal root ganglia, and in the trigeminal ganglion. The survival of γ -synuclein-deficient trigeminal neurons in various culture conditions was not different from that of wild-type neurons. There was no difference in the numbers of myelinated and nonmyelinated fibers in the saphenous nerves of these animals, and sensory reflex thresholds were also intact in γ-synuclein null mutant mice. Nerve injury led to similar changes in sensory function in wild-type and mutant mice. Taken together, our data suggest that like α-synuclein, γ-synuclein is dispensable for the development and function of the nervous system.