GeV Gamma-Ray Attenuation and the High-Redshift UV Background

We present new calculations of the evolving UV background out to the epoch of cosmological reionization and make predictions for the amount of GeV gamma-ray attenuation by electron-positron pair production. Our results are based on recent semi-analytic models of galaxy formation, which provide predictions of the dust-extinguished UV radiation field due to starlight, and empirical estimates of the contribution due to quasars. We account for the reprocessing of ionizing photons by the intergalactic medium. We test whether our models can reproduce estimates of the ionizing background at high redshift from flux decrement analysis and proximity effect measurements from quasar spectra, and identify a range of models that can satisfy these constraints. Pair-production against soft diffuse photons leads to a spectral cutoff feature for gamma rays observed between 10 and 100 GeV. This cutoff varies with redshift and the assumed star formation and quasar evolution models. We find only negligible amounts of absorption for gamma rays observed below 10 GeV for any emission redshift. With observations of high-redshift sources in sufficient numbers by the Fermi Gamma-ray Space Telescope and new ground-based instruments it should be possible to constrain the extragalactic background light in the UV and optical portion of the spectrum.Comment: 19 pages, 12 figures, Accepted for publication in MNRAS, this version includes minor correction

Divergent amino acid and sphingolipid metabolism in patients with inherited neuro-retinal disease

OBJECTIVES: The non-essential amino acids serine, glycine, and alanine, as well as diverse sphingolipid species, are implicated in inherited neuro-retinal disorders and are metabolically linked by serine palmitoyltransferase (SPT), a key enzyme in membrane lipid biogenesis. To gain insight into the pathophysiological mechanisms linking these pathways to neuro-retinal diseases we compared patients diagnosed with two metabolically intertwined diseases: macular telangiectasia type II (MacTel), hereditary sensory autonomic neuropathy type 1 (HSAN1), or both. METHODS: We performed targeted metabolomic analyses of amino acids and broad sphingolipids in sera from a cohort of MacTel (205), HSAN1 (25) and Control (151) participants. RESULTS: MacTel patients exhibited broad alterations of amino acids, including changes in serine, glycine, alanine, glutamate, and branched-chain amino acids reminiscent of diabetes. MacTel patients had elevated 1-deoxysphingolipids but reduced levels of complex sphingolipids in circulation. A mouse model of retinopathy indicates dietary serine and glycine restriction can drive this depletion in complex sphingolipids. HSAN1 patients exhibited elevated serine, lower alanine, and a reduction in canonical ceramides and sphingomyelins compared to controls. Those patients diagnosed with both HSAN1 and MacTel showed the most significant decrease in circulating sphingomyelins. CONCLUSIONS: These results highlight metabolic distinctions between MacTel and HSAN1, emphasize the importance of membrane lipids in the progression of MacTel, and suggest distinct therapeutic approaches for these two neurodegenerative diseases

Facial expressions depicting compassionate and critical emotions: the development and validation of a new emotional face stimulus set

Attachment with altruistic others requires the ability to appropriately process affiliative and kind facial cues. Yet there is no stimulus set available to investigate such processes. Here, we developed a stimulus set depicting compassionate and critical facial expressions, and validated its effectiveness using well-established visual-probe methodology. In Study 1, 62 participants rated photographs of actors displaying compassionate/kind and critical faces on strength of emotion type. This produced a new stimulus set based on N = 31 actors, whose facial expressions were reliably distinguished as compassionate, critical and neutral. In Study 2, 70 participants completed a visual-probe task measuring attentional orientation to critical and compassionate/kind faces. This revealed that participants lower in self-criticism demonstrated enhanced attention to compassionate/kind faces whereas those higher in self-criticism showed no bias. To sum, the new stimulus set produced interpretable findings using visual-probe methodology and is the first to include higher order, complex positive affect displays

Neurobehavioral consequences of chronic intrauterine opioid exposure in infants and preschool children: a systematic review and meta-analysis

<b>Background</b><p></p> It is assumed within the accumulated literature that children born of pregnant opioid dependent mothers have impaired neurobehavioral function as a consequence of chronic intrauterine opioid use.<p></p> <b>Methods</b><p></p> Quantitative and systematic review of the literature on the consequences of chronic maternal opioid use during pregnancy on neurobehavioral function of children was conducted using the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We searched Cinahl, EMBASE, PsychINFO and MEDLINE between the periods of January 1995 to January 2012.<p></p> <b>Results</b><p></p> There were only 5 studies out of the 200 identified that quantitatively reported on neurobehavioral function of children after maternal opioid use during pregnancy. All 5 were case control studies with the number of exposed subjects within the studies ranging from 33–143 and 45–85 for the controls. This meta-analysis showed no significant impairments, at a non-conservative significance level of p < 0.05, for cognitive, psychomotor or observed behavioural outcomes for chronic intra-uterine exposed infants and pre-school children compared to non-exposed infants and children. However, all domains suggested a trend to poor outcomes in infants/children of opioid using mothers. The magnitude of all possible effects was small according to Cohen’s benchmark criteria.<p></p> <b>Conclusions</b><p></p> Chronic intra-uterine opioid exposed infants and pre-school children experienced no significant impairment in neurobehavioral outcomes when compared to non-exposed peers, although in all domains there was a trend to poorer outcomes. The findings of this review are limited by the small number of studies analysed, the heterogenous populations and small numbers within the individual studies. Longitudinal studies are needed to determine if any neuropsychological impairments appear after the age of 5 years and to help investigate further the role of environmental risk factors on the effect of ‘core’ phenotypes

Horizontal DNA transfer mechanisms of bacteria as weapons of intragenomic conflict

Horizontal DNA transfer (HDT) is a pervasive mechanism of diversification in many microbial species, but its primary evolutionary role remains controversial. Much recent research has emphasised the adaptive benefit of acquiring novel DNA, but here we argue instead that intragenomic conflict provides a coherent framework for understanding the evolutionary origins of HDT. To test this hypothesis, we developed a mathematical model of a clonally descended bacterial population undergoing HDT through transmission of mobile genetic elements (MGEs) and genetic transformation. Including the known bias of transformation toward the acquisition of shorter alleles into the model suggested it could be an effective means of counteracting the spread of MGEs. Both constitutive and transient competence for transformation were found to provide an effective defence against parasitic MGEs; transient competence could also be effective at permitting the selective spread of MGEs conferring a benefit on their host bacterium. The coordination of transient competence with cell-cell killing, observed in multiple species, was found to result in synergistic blocking of MGE transmission through releasing genomic DNA for homologous recombination while simultaneously reducing horizontal MGE spread by lowering the local cell density. To evaluate the feasibility of the functions suggested by the modelling analysis, we analysed genomic data from longitudinal sampling of individuals carrying Streptococcus pneumoniae. This revealed the frequent within-host coexistence of clonally descended cells that differed in their MGE infection status, a necessary condition for the proposed mechanism to operate. Additionally, we found multiple examples of MGEs inhibiting transformation through integrative disruption of genes encoding the competence machinery across many species, providing evidence of an ongoing "arms race." Reduced rates of transformation have also been observed in cells infected by MGEs that reduce the concentration of extracellular DNA through secretion of DNases. Simulations predicted that either mechanism of limiting transformation would benefit individual MGEs, but also that this tactic's effectiveness was limited by competition with other MGEs coinfecting the same cell. A further observed behaviour we hypothesised to reduce elimination by transformation was MGE activation when cells become competent. Our model predicted that this response was effective at counteracting transformation independently of competing MGEs. Therefore, this framework is able to explain both common properties of MGEs, and the seemingly paradoxical bacterial behaviours of transformation and cell-cell killing within clonally related populations, as the consequences of intragenomic conflict between self-replicating chromosomes and parasitic MGEs. The antagonistic nature of the different mechanisms of HDT over short timescales means their contribution to bacterial evolution is likely to be substantially greater than previously appreciated

On the Integrand-Reduction Method for Two-Loop Scattering Amplitudes

We propose a first implementation of the integrand-reduction method for two-loop scattering amplitudes. We show that the residues of the amplitudes on multi-particle cuts are polynomials in the irreducible scalar products involving the loop momenta, and that the reduction of the amplitudes in terms of master integrals can be realized through polynomial fitting of the integrand, without any apriori knowledge of the integral basis. We discuss how the polynomial shapes of the residues determine the basis of master integrals appearing in the final result. We present a four-dimensional constructive algorithm that we apply to planar and non-planar contributions to the 4- and 5-point MHV amplitudes in N=4 SYM. The technique hereby discussed extends the well-established analogous method holding for one-loop amplitudes, and can be considered a preliminary study towards the systematic reduction at the integrand-level of two-loop amplitudes in any gauge theory, suitable for their automated semianalytic evaluation.Comment: 26 pages, 11 figure

A Comprehensive Model of Audiovisual Perception: Both Percept and Temporal Dynamics

The sparse information captured by the sensory systems is used by the brain to apprehend the environment, for example, to spatially locate the source of audiovisual stimuli. This is an ill-posed inverse problem whose inherent uncertainty can be solved by jointly processing the information, as well as introducing constraints during this process, on the way this multisensory information is handled. This process and its result - the percept - depend on the contextual conditions perception takes place in. To date, perception has been investigated and modeled on the basis of either one of two of its dimensions: the percept or the temporal dynamics of the process. Here, we extend our previously proposed audiovisual perception model to predict both these dimensions to capture the phenomenon as a whole. Starting from a behavioral analysis, we use a data-driven approach to elicit a Bayesian network which infers the different percepts and dynamics of the process. Context-specific independence analyses enable us to use the model's structure to directly explore how different contexts affect the way subjects handle the same available information. Hence, we establish that, while the percepts yielded by a unisensory stimulus or by the non-fusion of multisensory stimuli may be similar, they result from different processes, as shown by their differing temporal dynamics. Moreover, our model predicts the impact of bottom-up (stimulus driven) factors as well as of top-down factors (induced by instruction manipulation) on both the perception process and the percept itself

Fatal myocarditis in a child with systemic onset juvenile idiopathic arthritis during treatment with an interleukin 1 receptor antagonist

<p>Abstract</p> <p>Background</p> <p>The pathologic diagnosis of isolated myocarditis without pericardial involvement is uncommonly encountered in systemic onset Juvenile Idiopathic Arthritis (soJIA).</p> <p>Case</p> <p>An eleven year-old boy with soJIA died suddenly while being treated with the interleukin 1 (IL-1) receptor inhibitor, anakinra. His autopsy revealed an enlarged heart and microscopic findings were consistent with myocarditis, but not pericarditis. Viral PCR testing performed on his myocardial tissue was negative.</p> <p>Conclusion</p> <p>This case illustrates myocarditis as a fatal complication of soJIA, potentially enabled by anakinra.</p

The clinical and molecular spectrum of galactosemia in patients from the Cape Town region of South Africa

BACKGROUND: The objective of this study was to document the clinical, laboratory and genetic features of galactosemia in patients from the Cape Town metropolitan region. METHODS: Diagnoses were based on thin layer chromatography for galactosuria/galactosemia and assays of erythrocyte galactose-1-phosphate uridyltransferase (GALT) and galactokinase activities. Patients were screened for the common S135L and Q188R transferase gene mutations, using PCR-based assays. Screening for the S135L mutation in black newborns was used to estimate the carrier rate for galactosemia in black South Africans. RESULTS: A positive diagnosis of galactosemia was made in 17 patients between the years 1980 to 2001. All had very low or absent galactose-1-phosphate uridyltransferase (GALT) activity, and normal galactokinase levels. The mean age at diagnosis was 5.1 months (range 4 days to 6.5 months). A review of 9 patients showed that hepatomegaly (9/9), and splenomegaly, failure to thrive, developmental delay, bilateral cataracts (6/9) were the most frequent features at diagnosis. Six had conjugated hyperbilirubinemia. Four experienced invasive E. coli infection before diagnosis. Ten patients were submitted to DNA analysis. All 4 black patients and 2 of mixed extraction were homozygous for the S135L allele, while all 3 white patients were homozygous for the Q188R allele. The remaining patient of mixed extraction was heterozygous for the Q188R allele. The estimated carrier frequency of the S135L mutation in 725 healthy black newborns was 1/60. CONCLUSIONS: In the absence of newborn screening the delay in diagnosis is most often unacceptably long. Also, carrier frequency data predict a galactosemia incidence of approximately 1/14 400 for black newborns in the Cape Metropole, which is much higher than the current detection rate. It is thus likely that many patients go undetected