The volumetric rate of calcium-rich transients in the local universe

We present a measurement of the volumetric rate of `calcium-rich' optical transients in the local universe, using a sample of three events from the Palomar Transient Factory (PTF). This measurement builds on a detailed study of the PTF transient detection efficiencies, and uses a Monte Carlo simulation of the PTF survey. We measure the volumetric rate of calcium-rich transients to be higher than previous estimates: $1.21^{+1.13}_{-0.39}\times10^{-5}$ events yr$^{-1}$ Mpc$^{-3}$. This is equivalent to 33-94% of the local volumetric type Ia supernova rate. This calcium-rich transient rate is sufficient to reproduce the observed calcium abundances in galaxy clusters, assuming an asymptotic calcium yield per calcium-rich event of ~0.05$\mathrm{M}_{\odot}$. We also study the PTF detection efficiency of these transients as a function of position within their candidate host galaxies. We confirm as a real physical effect previous results that suggest calcium-rich transients prefer large physical offsets from their host galaxies.Comment: Accepted for publication in ApJ. 9 pages, 5 figure

Segmenting subregions of the human hippocampus on structural magnetic resonance image scans: An illustrated tutorial

BACKGROUND: The hippocampus plays a central role in cognition, and understanding the specific contributions of its subregions will likely be key to explaining its wide-ranging functions. However, delineating substructures within the human hippocampus in vivo from magnetic resonance image scans is fraught with difficulties. To our knowledge, the extant literature contains only brief descriptions of segmentation procedures used to delineate hippocampal subregions in magnetic resonance imaging/functional magnetic resonance imaging studies. // METHODS: Consequently, here we provide a clear, step-by-step and fully illustrated guide to segmenting hippocampal subregions along the entire length of the human hippocampus on 3T magnetic resonance images. // RESULTS: We give a detailed description of how to segment the hippocampus into the following six subregions: dentate gyrus/Cornu Ammonis 4, CA3/2, CA1, subiculum, pre/parasubiculum and the uncus. Importantly, this in-depth protocol incorporates the most recent cyto- and chemo-architectural evidence and includes a series of comprehensive figures which compare slices of histologically stained tissue with equivalent 3T images. // CONCLUSION: As hippocampal subregion segmentation is an evolving field of research, we do not suggest this protocol is definitive or final. Rather, we present a fully explained and expedient method of manual segmentation which remains faithful to our current understanding of human hippocampal neuroanatomy. We hope that this 'tutorial'-style guide, which can be followed by experts and non-experts alike, will be a practical resource for clinical and research scientists with an interest in the human hippocampus

The Rising Light Curves of Type Ia Supernovae

We present an analysis of the early, rising light curves of 18 Type Ia supernovae (SNe Ia) discovered by the Palomar Transient Factory (PTF) and the La Silla-QUEST variability survey (LSQ). We fit these early data flux using a simple power-law $(f(t) = {\alpha\times t^n})$ to determine the time of first light $({t_0})$, and hence the rise-time $({t_{rise}})$ from first light to peak luminosity, and the exponent of the power-law rise ($n$). We find a mean uncorrected rise time of $18.98 {\pm} 0.54$ days, with individual SN rise-times ranging from $15.98$ to $24.7$ days. The exponent n shows significant departures from the simple 'fireball model' of $n = 2$ (or ${f(t) \propto t^2}$) usually assumed in the literature. With a mean value of $n = 2.44 {\pm} 0.13$, our data also show significant diversity from event to event. This deviation has implications for the distribution of 56Ni throughout the SN ejecta, with a higher index suggesting a lesser degree of 56Ni mixing. The range of n found also confirms that the 56Ni distribution is not standard throughout the population of SNe Ia, in agreement with earlier work measuring such abundances through spectral modelling. We also show that the duration of the very early light curve, before the luminosity has reached half of its maximal value, does not correlate with the light curve shape or stretch used to standardise SNe Ia in cosmological applications. This has implications for the cosmological fitting of SN Ia light curves.Comment: 19 pages, 19 figures, accepted for publication in MNRA

Tonic inhibition of accumbal spiny neurons by extrasynaptic 4 GABAA receptors modulates the actions of psychostimulants

Within the nucleus accumbens (NAc), synaptic GABAA receptors (GABAARs) mediate phasic inhibition of medium spiny neurons (MSNs) and influence behavioral responses to cocaine. We demonstrate that both dopamine D1- and D2-receptor-expressing MSNs (D-MSNs) additionally harbor extrasynaptic GABAARs incorporating α4, β, and δ subunits that mediate tonic inhibition, thereby influencing neuronal excitability. Both the selective δ-GABAAR agonist THIP and DS2, a selective positive allosteric modulator, greatly increased the tonic current of all MSNs from wild-type (WT), but not from δ−/− or α4−/− mice. Coupling dopamine and tonic inhibition, the acute activation of D1 receptors (by a selective agonist or indirectly by amphetamine) greatly enhanced tonic inhibition in D1-MSNs but not D2-MSNs. In contrast, prolonged D2 receptor activation modestly reduced the tonic conductance of D2-MSNs. Behaviorally, WT and constitutive α4−/− mice did not differ in their expression of cocaine-conditioned place preference (CPP). Importantly, however, mice with the α4 deletion specific to D1-expressing neurons (α4D1−/−) showed increased CPP. Furthermore, THIP administered systemically or directly into the NAc of WT, but not α4−/− or α4D1−/− mice, blocked cocaine enhancement of CPP. In comparison, α4D2−/− mice exhibited normal CPP, but no cocaine enhancement. In conclusion, dopamine modulation of GABAergic tonic inhibition of D1- and D2-MSNs provides an intrinsic mechanism to differentially affect their excitability in response to psychostimulants and thereby influence their ability to potentiate conditioned reward. Therefore, α4βδ GABAARs may represent a viable target for the development of novel therapeutics to better understand and influence addictive behaviors

Decoding neuronal ensembles in the human hippocampus

BACKGROUND: The hippocampus underpins our ability to navigate, to form and recollect memories, and to imagine future experiences. How activity across millions of hippocampal neurons supports these functions is a fundamental question in neuroscience, wherein the size, sparseness, and organization of the hippocampal neural code are debated. RESULTS: Here, by using multivariate pattern classification and high spatial resolution functional MRI, we decoded activity across the population of neurons in the human medial temporal lobe while participants navigated in a virtual reality environment. Remarkably, we could accurately predict the position of an individual within this environment solely from the pattern of activity in his hippocampus even when visual input and task were held constant. Moreover, we observed a dissociation between responses in the hippocampus and parahippocampal gyrus, suggesting that they play differing roles in navigation. CONCLUSIONS: These results show that highly abstracted representations of space are expressed in the human hippocampus. Furthermore, our findings have implications for understanding the hippocampal population code and suggest that, contrary to current consensus, neuronal ensembles representing place memories must be large and have an anisotropic structure

The p53Pro72Arg Polymorphism is Associated with Albuminuria among Aboriginal Australians

Albuminuria is a widely recognized marker of renal disease and cardiovascular risk. This is especially true in Aboriginal Australians living in remote communities who suffer high rates of end-stage renal disease and cardiovascular mortality. During a survey of risk factors for renal and cardiovascular disease in one such community, an association between a common polymorphism at codon 72 (Arg/Pro) of the p53 gene and markers of renal disease was sought. A cross-sectional community survey including 217 people was performed. Genotypes of the polymorphism were distributed in Hardy-Weinberg equilibrium, with p53Arg allele frequency of 0.45 (range, 0.41 to 0.50). Overall prevalence of albuminuria was high (31% microalbuminuria; 14% overt albuminuria). Urine albumin/creatinine ratio (ACR) was significantly associated with the number of p53Pro alleles (P = 0.01), and there was an interaction with tobacco smoking (P = 0.04). The p53 genotype was also associated with increasing HbA1c, but the relationship between p53 and ACR was independent of this. This is a previously unreported association. This study does not address the mechanism, but this finding, if confirmed, expands the described effects of p53 in cellular proliferation and apoptosis to include a role in the course of renal and possibly cardiovascular disease in this population

The dual endothelin converting enzyme/neutral endopeptidase inhibitor SLV-306 (daglutril), inhibits systemic conversion of big endothelin-1 in humans

Aims - Inhibition of neutral endopeptidases (NEP) results in a beneficial increase in plasma concentrations of natriuretic peptides such as ANP. However NEP inhibitors were ineffective anti-hypertensives, probably because NEP also degrades vasoconstrictor peptides, including endothelin-1 (ET-1). Dual NEP and endothelin converting enzyme (ECE) inhibition may be more useful. The aim of the study was to determine whether SLV-306 (daglutril), a combined ECE/NEP inhibitor, reduced the systemic conversion of big ET-1 to the mature peptide. Secondly, to determine whether plasma ANP levels were increased. Main methods - Following oral administration of three increasing doses of SLV-306 (to reach an average target concentration of 75, 300, 1200 ng ml− 1 of the active metabolite KC-12615), in a randomised, double blinded regime, big ET-1 was infused into thirteen healthy male volunteers. Big ET-1 was administered at a rate of 8 and 12 pmol kg− 1 min− 1 (20 min each). Plasma samples were collected pre, during and post big ET-1 infusion. ET-1, C-terminal fragment (CTF), big ET-1, and atrial natriuretic peptide (ANP) were measured. Key findings - At the two highest concentrations tested, SLV-306 dose dependently attenuated the rise in blood pressure after big ET-1 infusion. There was a significant increase in circulating big ET-1 levels, compared with placebo, indicating that SLV-306 was inhibiting an increasing proportion of endogenous ECE activity. Plasma ANP concentrations also significantly increased, consistent with systemic NEP inhibition. Significance - SLV-306 leads to inhibition of both NEP and ECE in humans. Simultaneous augmentation of ANP and inhibition of ET-1 production is of potential therapeutic benefit in cardiovascular disease

A New Automated Way to Measure Polyethylene Wear in THA Using a High Resolution CT Scanner: Method and Analysis

As the most advantageous total hip arthroplasty (THA) operation is the first, timely replacement of only the liner is socially and economically important because the utilization of THA is increasing as younger and more active patients are receiving implants and they are living longer. Automatic algorithms were developed to infer liner wear by estimating the separation between the acetabular cup and femoral component head given a computed tomography (CT) volume. Two series of CT volumes of a hip phantom were acquired with the femoral component head placed at 14 different positions relative to the acetabular cup. The mean and standard deviation (SD) of the diameter of the acetabular cup and femoral component head, in addition to the range of error in the expected wear values and the repeatability of all the measurements, were calculated. The algorithms resulted in a mean (±SD) for the diameter of the acetabular cup of 54.21 (±0.011) mm and for the femoral component head of 22.09 (±0.02) mm. The wear error was ±0.1 mm and the repeatability was 0.077 mm. This approach is applicable clinically as it utilizes readily available computed tomography imaging systems and requires only five minutes of human interaction

Autobiographical memory: A candidate latent vulnerability mechanism for psychiatric disorder following childhood maltreatment

BACKGROUND: Altered autobiographical memory (ABM) functioning has been implicated in the pathogenesis of depression and post-traumatic stress disorder and may represent one mechanism by which childhood maltreatment elevates psychiatric risk. AIMS: To investigate the impact of childhood maltreatment on ABM functioning. METHOD: Thirty-four children with documented maltreatment and 33 matched controls recalled specific ABMs in response to emotionally-valenced cue words during functional magnetic resonance imaging (fMRI). RESULTS: Children with maltreatment experience showed reduced hippocampal and increased middle temporal and para-hippocampal activation during positive ABM recall compared to peers. During negative ABM recall they exhibited increased amygdala activation, and greater amygdala connectivity with the salience network. CONCLUSIONS: Childhood maltreatment is associated with altered ABM functioning, specifically reduced activation in areas encoding specification of positive memories, and greater activation of the salience network for negative memories. This pattern may confer latent vulnerability to future depression and post-traumatic stress disorder