Missing Power vs low-l Alignments in the Cosmic Microwave Background: No Correlation in the Standard Cosmological Model

On large angular scales (greater than about 60 degrees), the two-point angular correlation function of the temperature of the cosmic microwave background (CMB), as measured (outside of the plane of the Galaxy) by the Wilkinson Microwave Anisotropy Probe, shows significantly lower large-angle correlations than expected from the standard inflationary cosmological model. Furthermore, when derived from the full CMB sky, the two lowest cosmologically interesting multipoles, the quadrupole (l=2) and the octopole (l=3), are unexpectedly aligned with each other. Using randomly generated full-sky and cut-sky maps, we investigate whether these anomalies are correlated at a statistically significant level. We conclusively demonstrate that, assuming Gaussian random and statistically isotropic CMB anisotropies, there is no statistically significant correlation between the missing power on large angular scales in the CMB and the alignment of the l=2 and l=3 multipoles. The chance to measure the sky with both such a lack of large-angle correlation and such an alignment of the low multipoles is thus quantified to be below 10^{-6}.Comment: 4 Pages, 1 Figur

The Virtues of Frugality - Why cosmological observers should release their data slowly

Cosmologists will soon be in a unique position. Observational noise will gradually be replaced by cosmic variance as the dominant source of uncertainty in an increasing number of observations. We reflect on the ramifications for the discovery and verification of new models. If there are features in the full data set that call for a new model, there will be no subsequent observations to test that model's predictions. We give specific examples of the problem by discussing the pitfalls of model discovery by prior adjustment in the context of dark energy models and inflationary theories. We show how the gradual release of data can mitigate this difficulty, allowing anomalies to be identified, and new models to be proposed and tested. We advocate that observers plan for the frugal release of data from future cosmic variance limited observations.Comment: 5 pages, expanded discussion of Lambda and of blind anlysis, added refs. Matches version to appear in MNRAS Letter

RAF inhibitors activate the integrated stress response by direct activation of GCN2

Paradoxical RAF activation by chemical RAF inhibitors (RAFi) is a well-understood on-target biological and clinical response. In this study, we show that a range of RAFi drive ERK1/2-independent activation of the Unfolded Protein Response (UPR), including expression of ATF4 and CHOP, that required the translation initiation factor eIF2-alpha. RAFi-induced ATF4 and CHOP expression was not reversed by inhibition of PERK, a known upstream activator of the eIF2-alpha-dependent Integrated Stress Response (ISR). Rather, we found that RAFi exposure activated GCN2, an alternate eIF2-alpha kinase, leading to eIF2-alpha-dependent (and ERK1/2-independent) ATF4 and CHOP expression. The GCN2 kinase inhibitor A-92, GCN2 RNAi, GCN2 knock-out or ISRIB (an eIF2-alpha antagonist) all reversed RAFi-induced expression of ATF4 and CHOP indicating that RAFi require GCN2 to activate the ISR. RAFi also activated full-length recombinant GCN2 in vitro and in cells, generating a characteristic bell-shaped concentration-response curve, reminiscent of RAFi-driven paradoxical activation of WT RAF dimers. Activation of the ISR by RAFi was abolished by GCN2 kinase dead mutations and M802A or M802G gatekeeper mutations, suggesting that RAFi bind directly to the GCN2 kinase domain; this was supported by mechanistic structural models of RAFi interaction with GCN2. Since the ISR is a critical pathway for determining cell survival or death, our observations may be relevant to the clinical use of RAFi, where paradoxical GCN2 activation may be a previously unappreciated off-target effect that may modulate tumour cell responses

High-Resolution Oscillator Strength Measurements of the v\u27 = 0,1 Bands of the B-X, C-X, and E-X Systems in Five Isotopologues of Carbon Monoxide

We report oscillator strengths for six strong vibrational bands between 105.0 and 115.2 nm, associated with transitions from the v = 0 level of the X 1Σ+ ground state to the v = 0 and 1 levels of the B 1Σ+, C 1Σ+, and E 1Π states, in 12C16O, 12C17O, 12C18O, 13C16O, and 13C18O. These measurements extend the development of a comprehensive database of line positions, oscillator strengths, and linewidths of photodissociating transitions for all astrophysically relevant CO isotopologues. The E–X bands, in particular, play central roles in CO photodissociation and fractionationmodels of interstellar clouds and circumstellar disks including the early solar nebula. The resolving powers of the room-temperature measurements, R = 300,000–400,000, allow for the analysis of individual line strengths within bands; the measurements reveal J-dependences in the branch intensities of the C(v = 0,1)–X(0) and E(v = 0,1)–X(0) bands in all isotopologues. Minimal or no isotopologue dependence was found in the f-values of the C(v = 0,1)–X(0) and E(v = 0,1)–X(0) bands at a ∼5% uncertainty level. Revised dissociation branching ratios for the C(v = 0,1) and E(v = 0,1) levels are computed based on these f-values. The weak isotopologue dependence of the f-values presented here eliminates this mechanism as an explanation for the large 17O enrichments seen in recent laboratory photolysis experiments on CO at wavelengths from 105 to 108 nm

Bias in low‐multipole cosmic microwave background reconstructions

The large‐angle, low‐multipole cosmic microwave background (CMB) provides a unique view of the largest angular scales in the Universe. Study of these scales is hampered by the facts that we have only one Universe to observe, only a few independent samples of the underlying statistical distribution of these modes, and an incomplete sky to observe due to the interposing Galaxy. Techniques for reconstructing a full sky from partial‐sky data are well known and have been applied to the large angular scales. In this work, we critically study the reconstruction process and show that, in practice, the reconstruction is biased due to leakage of information from the region obscured by foregrounds to the region used for the reconstruction. We conclude that, despite being suboptimal in a technical sense, using the unobscured region without reconstructing is the most robust measure of the true CMB sky. We also show that for noise‐free data reconstructing using the usual optimal, unbiased estimator may be employed without smoothing, thus avoiding the leakage problem. Unfortunately, directly applying this to real data with noise and residual, unmasked foregrounds yields highly biased reconstructions requiring further care to apply this method successfully to the real‐world CMB.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/88089/1/j.1365-2966.2011.19511.x.pd

No large-angle correlations on the non-Galactic microwave sky

We investigate the angular two-point correlation function of temperature in the WMAP maps. Updating and extending earlier results, we confirm the lack of correlations outside the Galaxy on angular scales greater than about 60 degrees at a level that would occur in 0.025 per cent of realizations of the concordance model. This represents a dramatic increase in significance from the original observations by the COBE-DMR and a marked increase in significance from the first-year WMAP maps. Given the rest of the reported angular power spectrum C_\ell, the lack of large-angle correlations that one infers outside the plane of the Galaxy requires covariance among the C_\ell up to \ell=5. Alternately, it requires both the unusually small (5 per cent of realizations) full-sky large-angle correlations, and an unusual coincidence of alignment of the Galaxy with the pattern of cosmological fluctuations (less than 2 per cent of those 5 per cent). We argue that unless there is some undiscovered systematic error in their collection or reduction, the data point towards a violation of statistical isotropy. The near-vanishing of the large-angle correlations in the cut-sky maps, together with their disagreement with results inferred from full-sky maps, remain open problems, and are very difficult to understand within the concordance model.Comment: 9 pages, 2 figures, updated with corrections in published versio

Gambling disorder and suicide: An overview of the associated co-morbidity and clinical characteristics

Context: A high prevalence of suicide and attempted suicide in relation to gambling disorder is in increasing evidence in current scientific data. The objective of this review was to explore if there was a primary correlation between psychiatric co-morbidities and gambling and/or a secondary correlation with suicide acts. Evidence Acquisition: We performed a critical analysis of the most recent papers in the scientific literature in this regard and report on the most significant findings. Results: A direct relationship between gambling and suicidality was highlighted in a number of European, American, and Asian countries. However, it was not clear whether or not gambling increased the risk of suicidal behavior. Twogeneral trends were noted. The first was that gamblers with extreme gambling behavior incurred economic losses and debts to such an extent that suicidal acts appeared to be the only solution. The second was that suicidal acts by gamblers were precipitated by interpersonal and/or working challenges, in conjunction with personality traits of impulsivity and psychiatric co-morbidities. Conclusions: A combination of impulsivity, certain psychiatric disorders, and social factors may explain the frequent occurrence of suicidal behavior in gamblers

Trends in prevalence, mortality, and morbidity associated with high systolic blood pressure in Brazil from 1990 to 2017 : estimates from the “Global Burden of Disease 2017” (GBD 2017) study

Background: Hypertension remains the leading risk factor for cardiovascular disease (CVD) worldwide, and its impact in Brazil should be assessed in order to better address the issue. We aimed to describe trends in prevalence and burden of disease attributable to high systolic blood pressure (HSBP) among Brazilians ≥ 25 years old according to sex and federal units (FU) using the Global Burden of Disease (GBD) 2017 estimates. Methods: We used the comparative risk assessment developed for the GBD study to estimate trends in attributable deaths and disability-adjusted life-years (DALY), by sex, and FU for HSBP from 1990 to 2017. This study included 14 HSBP-outcome pairs. HSBP was defined as ≥ 140 mmHg for prevalence estimates, and a theoretical minimum risk exposure level (TMREL) of 110–115 mmHg was considered for disease burden. We estimated the portion of deaths and DALYs attributed to HSBP. We also explored the drivers of trends in HSBP burden, as well as the correlation between disease burden and sociodemographic development index (SDI). Results: In Brazil, the prevalence of HSBP is 18.9% (95% uncertainty intervals [UI] 18.5–19.3%), with an annual 0.4% increase rate, while age-standardized death rates attributable to HSBP decreased from 189.2 (95%UI 168.5–209.2) deaths to 104.8 (95%UI 94.9–114.4) deaths per 100,000 from 1990 to 2017. In spite of that, the total number of deaths attributable to HSBP increased 53.4% and HSBP raised from 3rd to 1st position, as the leading risk factor for deaths during the period. Regarding total DALYs, HSBP raised from 4th in 1990 to 2nd cause in 2017. The main driver of change of HSBP burden is population aging. Across FUs, the reduction in the age-standardized death rates attributable to HSBP correlated with higher SDI. Conclusions: While HSBP prevalence shows an increasing trend, age-standardized death and DALY rates are decreasing in Brazil, probably as results of successful public policies for CVD secondary prevention and control, but suboptimal control of its determinants. Reduction was more significant in FUs with higher SDI, suggesting that the effect of health policies was heterogeneous. Moreover, HSBP has become the main risk factor for death in Brazil, mainly due to population aging