Post-Newtonian accurate parametric solution to the dynamics of spinning compact binaries in eccentric orbits: The leading order spin-orbit interaction

We derive Keplerian-type parametrization for the solution of post-Newtonian (PN) accurate conservative dynamics of spinning compact binaries moving in eccentric orbits. The PN accurate dynamics that we consider consists of the third post-Newtonian accurate conservative orbital dynamics influenced by the leading order spin effects, namely the leading order spin-orbit interactions. The orbital elements of the representation are explicitly given in terms of the conserved orbital energy, angular momentum and a quantity that characterizes the leading order spin-orbit interactions in Arnowitt, Deser, and Misner-type coordinates. Our parametric solution is applicable in the following two distinct cases: (i) the binary consists of equal mass compact objects, having two arbitrary spins, and (ii) the binary consists of compact objects of arbitrary mass, where only one of them is spinning with an arbitrary spin. As an application of our parametrization, we present gravitational wave polarizations, whose amplitudes are restricted to the leading quadrupolar order, suitable to describe gravitational radiation from spinning compact binaries moving in eccentric orbits. The present parametrization will be required to construct `ready to use' reference templates for gravitational waves from spinning compact binaries in inspiralling eccentric orbits. Our parametric solution for the post-Newtonian accurate conservative dynamics of spinning compact binaries clearly indicates, for the cases considered, the absence of chaos in these systems. Finally, we note that our parametrization provides the first step in deriving a fully second post-Newtonian accurate `timing formula', that may be useful for the radio observations of relativistic binary pulsars like J0737-3039.Comment: 18 pages, accepted by Phys. Rev.

Canonical formalism for the Born-Infeld particle

In the previous paper (hep-th/9712161) it was shown that the nonlinear Born-Infeld field equations supplemented by the "dynamical condition" (certain boundary condition for the field along the particle's trajectory) define perfectly deterministic theory, i.e. particle's trajectory is determined without any equations of motion. In the present paper we show that this theory possesses mathematically consistent Lagrangian and Hamiltonian formulations. Moreover, it turns out that the "dynamical condition" is already present in the definition of the physical phase space and, therefore, it is a basic element of the theory.Comment: 14 pages, LATE

Evaluation of updated Feed Saved breeding values developed in Australian Holstein dairy cattle.

Although selection for increased milk production traits has led to a genetic increase in body weight (BW), the genetic gain in milk production has exceeded the gain in BW, so gross feed efficiency has improved. Nonetheless, greater gains may be possible by directly selecting for a measure of feed efficiency. Australia first introduced Feed Saved (FS) estimated breeding value (EBV) in 2015. Feed Saved combines residual feed intake (RFI) genomic EBV and maintenance requirements calculated from mature BW EBV. The FS EBV was designed to enable the selection of cows for reduced energy requirements with similar milk production. In this study, we used a reference population of 3,711 animals in a multivariate analysis including Australian heifers (AUSh), Australian cows (AUSc), and overseas cows (OVEc) to update the Australian EBV for lifetime RFI (i.e., a breeding value that incorporated RFI in growing and lactating cows) and to recalculate the FS EBV in Australian Holstein bulls (AUSb). The estimates of genomic heritabilities using univariate (only AUSc or AUSh) to trivariate (including the OVEc) analyses were similar. Genomic heritabilities for RFI were estimated as 0.18 for AUSc, 0.27 for OVEc, and 0.36 for AUSh. The genomic correlation for RFI between AUSc and AUSh was 0.47 and that between AUSc and OVEc was 0.94, but these estimates were associated with large standard errors (range: 0.18-0.28). The reliability of lifetime RFI (a component of FS) in the trivariate analysis (i.e., including OVEc) increased from 11% to 20% compared with the 2015 model and was greater, by 12%, than in a bivariate analysis in which the reference population included only AUSc and AUSh. By applying the prediction equation of the 2020 model, the average reliability of the FS EBV in 20,816 AUSb that were born between 2010 and 2020 improved from 33% to 43%. Previous selection strategies-that is, using the predecessor of the Balanced Performance Index (Australian Profit Ranking index) that did not include FS-have resulted in an unfavorable genetic trend in FS. However, this unfavorable trend has stabilized since 2015, when FS was included in the Balanced Performance Index, and is expected to move in a favorable direction with selection on Balanced Performance Index or the Health Weighted Index. Doubling the reference population, particularly by incorporating international data for feed efficiency, has improved the reliability of the FS EBV. This could lead to increased genetic gain for feed efficiency in the Australian industry

Potentially preventable infant and child deaths identified at autopsy; findings and implications

Purpose The purpose of the study was to determine the proportion of pediatric deaths investigated by HM Coronial autopsy which were potentially preventable deaths due to treatable natural disease, and what implications such findings may have for health policies to reduce their occurrence. Methods A retrospective study of 1779 autopsies of individuals between 7 days and 14 years of age requested by HM Coroner, taking place in one specialist pediatric autopsy center, was undertaken. Cases were included if they involved a definite natural disease process in which appropriate recognition and treatment was likely to have affected their outcome. Strict criteria were used and cases were excluded where the individual had any longstanding condition which might have predisposed them to, or altered the recognition of, acute illness, or its response to therapy. Results Almost 8 % (134/1779) of the study group were potentially preventable deaths as a result of natural disease, the majority occurring in children younger than 2 years of age. Most individuals reported between 1 and 7 days of symptoms before their death, and the majority had sought medical advice during this period, including from general practitioners within working hours, and hospital emergency departments. Of those who had sought medical attention, around one-third had done so more than once (28 %, 15/53). Sepsis and pneumonia accounted for the majority of deaths (46 and 34 % respectively), with all infections (sepsis, pneumonia and meningitis) accounting for 110/134 (82 %). Conclusion Around 10 % of pediatric deaths referred to HM Coroner are potentially preventable, being the result of treatable natural acute illnesses. In many cases medical advice had been sought during the final illness. The results highlight how a review of autopsy data can identify significant findings with the potential to reduce mortality, and the importance of centralized investigation and reporting of pediatric deaths

Genetic Background Can Result in a Marked or Minimal Effect of Gene Knockout (GPR55 and CB2 Receptor) in Experimental Autoimmune Encephalomyelitis Models of Multiple Sclerosis

PMCID: PMC379391

Einstein-Podolsky-Rosen-Bohm experiment with relativistic massive particles

The EPRB experiment with massive partcles can be formulated if one defines spin in a relativistic way. Two versions are discussed: The one using the spin operator defined via the relativistic center-of-mass operator, and the one using the Pauli-Lubanski vector. Both are shown to lead to the SAME prediction for the EPRB experiment: The degree of violation of the Bell inequality DECREASES with growing velocity of the EPR pair of spin-1/2 particles. The phenomenon can be physically understood as a combined effect of the Lorentz contraction and the Moller shift of the relativistic center of mass. The effect is therefore stronger than standard relativistic phenomena such as the Lorentz contraction or time dilatation. The fact that the Bell inequality is in general less violated than in the nonrelativistic case will have to be taken into account in tests for eavesdropping if massive particles will be used for a key transfer.Comment: Figures added as appeared in PRA, two typos corrected (one important in the formula for eigenvector in Sec. IV); link to the unpublished 1984 paper containing the results (without typos!) of Sec. IV is adde

The developmental impact of prenatal stress, prenatal dexamethasone and postnatal social stress on physiology, behaviour and neuroanatomy of primate offspring: studies in rhesus macaque and common marmoset

RATIONALE: Exposure of the immature mammalian brain to stress factors, including stress levels of glucocorticoids, either prenatally or postnatally, is regarded as a major regulatory factor in short- and long-term brain function and, in human, as a major aetiological factor in neuropsychiatric disorders. Experimental human studies are not feasible and animal studies are required to demonstrate causality and elucidate mechanisms. A number of studies have been conducted and reviewed in rodents but there are relatively few studies in primates. OBJECTIVES: Here we present an overview of our published studies and some original data on the effects of: (1) prenatal stress on hypothalamic-pituitary-adrenal (HPA) re/activity and hippocampus neuroanatomy in juvenile-adolescent rhesus macaques; (2) prenatal dexamethasone (DEX) on HPA activity, behaviour and prefrontal cortex neuroanatomy in infant-adolescent common marmosets; (3) postnatal daily parental separation stress on HPA re/activity, behaviour, sleep and hippocampus and prefrontal cortex neuroanatomy in infant-adolescent common marmoset. RESULTS: Prenatal stress increased basal cortisol levels and reduced neurogenesis in macaque. Prenatal DEX was without effect on HPA activity and reduced social play and skilled motor behaviour in marmoset. Postnatal social stress increased basal cortisol levels, reduced social play, increased awakening and reduced hippocampal glucocorticoid and mineralocorticoid receptor expression in marmoset. CONCLUSIONS: Perinatal stress-related environmental events exert short- and long-term effects on HPA function, behaviour and brain status in rhesus macaque and common marmoset. The mechanisms mediating the enduring effects remain to be elucidated, with candidates including increased basal HPA function and epigenetic programming

Sharing of either phenotypes or genetic variants can increase the accuracy of genomic prediction of feed efficiency.

BACKGROUND Sharing individual phenotype and genotype data between countries is complex and fraught with potential errors, while sharing summary statistics of genome-wide association studies (GWAS) is relatively straightforward, and thus would be especially useful for traits that are expensive or difficult-to-measure, such as feed efficiency. Here we examined: (1) the sharing of individual cow data from international partners; and (2) the use of sequence variants selected from GWAS of international cow data to evaluate the accuracy of genomic estimated breeding values (GEBV) for residual feed intake (RFI) in Australian cows. RESULTS GEBV for RFI were estimated using genomic best linear unbiased prediction (GBLUP) with 50k or high-density single nucleotide polymorphisms (SNPs), from a training population of 3797 individuals in univariate to trivariate analyses where the three traits were RFI phenotypes calculated using 584 Australian lactating cows (AUSc), 824 growing heifers (AUSh), and 2526 international lactating cows (OVE). Accuracies of GEBV in AUSc were evaluated by either cohort-by-birth-year or fourfold random cross-validations. GEBV of AUSc were also predicted using only the AUS training population with a weighted genomic relationship matrix constructed with SNPs from the 50k array and sequence variants selected from a meta-GWAS that included only international datasets. The genomic heritabilities estimated using the AUSc, OVE and AUSh datasets were moderate, ranging from 0.20 to 0.36. The genetic correlations (rg) of traits between heifers and cows ranged from 0.30 to 0.95 but were associated with large standard errors. The mean accuracies of GEBV in Australian cows were up to 0.32 and almost doubled when either overseas cows, or both overseas cows and AUS heifers were included in the training population. They also increased when selected sequence variants were combined with 50k SNPs, but with a smaller relative increase. CONCLUSIONS The accuracy of RFI GEBV increased when international data were used or when selected sequence variants were combined with 50k SNP array data. This suggests that if direct sharing of data is not feasible, a meta-analysis of summary GWAS statistics could provide selected SNPs for custom panels to use in genomic selection programs. However, since this finding is based on a small cross-validation study, confirmation through a larger study is recommended

Big conductance calcium-activated potassium channel openers control spasticity without sedation.

BACKGROUND AND PURPOSE: Our initial aim was to generate cannabinoid agents that control spasticity, occurring as a consequence of multiple sclerosis (MS), whilst avoiding the sedative side effects associated with cannabis. VSN16R was synthesized as an anandamide (endocannabinoid) analogue in an anti-metabolite approach to identify drugs that target spasticity. EXPERIMENTAL APPROACH: Following the initial chemistry, a variety of biochemical, pharmacological and electrophysiological approaches, using isolated cells, tissue-based assays and in vivo animal models, were used to demonstrate the activity, efficacy, pharmacokinetics and mechanism of action of VSN16R. Toxicological and safety studies were performed in animals and humans. KEY RESULTS: VSN16R had nanomolar activity in tissue-based, functional assays and dose-dependently inhibited spasticity in a mouse experimental encephalomyelitis model of MS. This effect occurred with over 1000-fold therapeutic window, without affecting normal muscle tone. Efficacy was achieved at plasma levels that are feasible and safe in humans. VSN16R did not bind to known CB1 /CB2 /GPPR55 cannabinoid-related receptors in receptor-based assays but acted on a vascular cannabinoid target. This was identified as the major neuronal form of the big conductance, calcium-activated potassium (BKCa ) channel. Drug-induced opening of neuronal BKCa channels induced membrane hyperpolarization, limiting excessive neural-excitability and controlling spasticity. CONCLUSIONS AND IMPLICATIONS: We identified the neuronal form of the BKCa channel as the target for VSN16R and demonstrated that its activation alleviates neuronal excitability and spasticity in an experimental model of MS, revealing a novel mechanism to control spasticity. VSN16R is a potential, safe and selective ligand for controlling neural hyper-excitability in spasticity