Observational constraints on an inflation model with a running mass

We explore a model of inflation where the inflaton mass-squared is generated at a high scale by gravity-mediated soft supersymmetry breaking, and runs at lower scales to the small value required for slow-roll inflation. The running is supposed to come from the coupling of the inflaton to a non-Abelian gauge field. In contrast with earlier work, we do not constrain the magnitude of the supersymmetry breaking scale, and we find that the model might work even if squark and slepton masses come from gauge-mediated supersymmetry breaking. With the inflaton and gaugino masses in the expected range, and $\alpha = g^2/4\pi$ in the range $10^{-2}$ to $10^{-3}$ (all at the high scale) the model can give the observed cosmic microwave anisotropy, and a spectral index in the observed range. The latter has significant variation with scale, which can confirm or rule out the model in the forseeable future.Comment: Latex, 19 pages, 14 figures, uses epsf.st

Evidence from Cameroon reveals differences in the genetic structure and histories of chimpanzee populations

The history of the genus Pan is a topic of enduring interest. Chimpanzees (Pan troglodytes) are often divided into subspecies, but the population structure and genetic history of chimpanzees across Africa remain unclear. Some population genetics studies have led to speculation that, until recently, this species constituted a single population with ongoing gene flow across its range, which resulted in a continuous gradient of allele frequencies. Chimpanzees, designated here as P. t. ellioti, occupy the Gulf of Guinea region that spans southern Nigeria and western Cameroon at the center of the distribution of this species. Remarkably, few studies have included individuals from this region, hindering the examination of chimpanzee population structure across Africa. Here, we analyzed microsatellite genotypes of 94 chimpanzees, including 32 designated as P. t. ellioti. We find that chimpanzees fall into three major populations: (i) Upper Guinea in western Africa (P. t. verus); (ii) the Gulf of Guinea region (P. t. ellioti); and (iii) equatorial Africa (P. t. troglodytes and P. t. schweinfurthii). Importantly, the Gulf of Guinea population is significantly different genetically from the others, sharing a last common ancestor with the populations in Upper Guinea similar to 0.46 million years ago (mya) and equatorial Africa similar to 0.32 mya. Equatorial chimpanzees are subdivided into up to three populations occupying southern Cameroon, central Africa, and eastern Africa, which may have constituted a single population until similar to 0.10-0.11 mya. Finally, occasional hybridization may be occurring between the Gulf of Guinea and southern Cameroon population

Pseudogap formation of four-layer BaRuO3_3 and its electrodynamic response changes

We investiaged the optical properties of four-layer BaRuO$_{3}$, which shows a fermi-liquid-like behavior at low temperature. Its optical conductivity spectra clearly displayed the formation of a pseudogap and the development of a coherent peak with decreasing temperature. Temperature-dependences of the density $n$ and the scattering rate $1/\tau$ of the coherent component were also derived. As the temperature decreases, both $n$ and $1/\tau$ decrease for four-layer BaRuO$_{3}$. These electrodynamic responses were compared with those of nine-layer BaRuO$_{3}$, which also shows a pseudogap formation but has an insulator-like state at low temperature. It was found that the relative rates of change of both $n$ and $1/\tau$ determine either metallic or insulator-like responses in the ruthenates. The optical properties of the four-layer ruthenate were also compared with those of other pseudogap systems, such as high $T_{c}$ cuprates and heavy electron systems.Comment: 7 figures. submitted to Phys. Rev.

Particle physics models of inflation

Inflation models are compared with observation on the assumption that the curvature perturbation is generated from the vacuum fluctuation of the inflaton field. The focus is on single-field models with canonical kinetic terms, classified as small- medium- and large-field according to the variation of the inflaton field while cosmological scales leave the horizon. Small-field models are constructed according to the usual paradigm for beyond Standard Model physicsComment: Based on a talk given at the 22nd IAP Colloquium, ``Inflation +25'', Paris, June 2006 Curve omitted from final Figur

Risk of Bias Assessments and Evidence Syntheses for Observational Epidemiologic Studies of Environmental and Occupational Exposures: Strengths and Limitations.

BACKGROUND: Increasingly, risk of bias tools are used to evaluate epidemiologic studies as part of evidence synthesis (evidence integration), often involving meta-analyses. Some of these tools consider hypothetical randomized controlled trials (RCTs) as gold standards. METHODS: We review the strengths and limitations of risk of bias assessments, in particular, for reviews of observational studies of environmental exposures, and we also comment more generally on methods of evidence synthesis. RESULTS: Although RCTs may provide a useful starting point to think about bias, they do not provide a gold standard for environmental studies. Observational studies should not be considered inherently biased vs. a hypothetical RCT. Rather than a checklist approach when evaluating individual studies using risk of bias tools, we call for identifying and quantifying possible biases, their direction, and their impacts on parameter estimates. As is recognized in many guidelines, evidence synthesis requires a broader approach than simply evaluating risk of bias in individual studies followed by synthesis of studies judged unbiased, or with studies given more weight if judged less biased. It should include the use of classical considerations for judging causality in human studies, as well as triangulation and integration of animal and mechanistic data. CONCLUSIONS: Bias assessments are important in evidence synthesis, but we argue they can and should be improved to address the concerns we raise here. Simplistic, mechanical approaches to risk of bias assessments, which may particularly occur when these tools are used by nonexperts, can result in erroneous conclusions and sometimes may be used to dismiss important evidence. Evidence synthesis requires a broad approach that goes beyond assessing bias in individual human studies and then including a narrow range of human studies judged to be unbiased in evidence synthesis. https://doi.org/10.1289/EHP6980

Probabilistic Reachability for Parametric Markov Models

Abstract. Given a parametric Markov model, we consider the problem of computing the formula expressing the probability of reaching a given set of states. To attack this principal problem, Daws has suggested to first convert the Markov chain into a finite automaton, from which a regular expression is computed. Afterwards, this expression is evaluated to a closed form expression representing the reachability probability. This paper investigates how this idea can be turned into an effective procedure. It turns out that the bottleneck lies in an exponential growth of the regular expression relative to the number of states. We therefore proceed differently, by tightly intertwining the regular expression computation with its evaluation. This allows us to arrive at an effective method that avoids the exponential blow up in most practical cases. We give a detailed account of the approach, also extending to parametric models with rewards and with non-determinism. Experimental evidence is provided, illustrating that our implementation provides meaningful insights on non-trivial models.

Cerebrovascular effects of sildenafil in small vessel disease: the OxHARP trial

BACKGROUND: Vascular cognitive impairment due to cerebral small vessel disease is associated with cerebral pulsatility, white matter hypoperfusion, and reduced cerebrovascular reactivity (CVR), and is potentially improved by endothelium-targeted drugs such as cilostazol. Whether sildenafil, a phosphodiesterase-5 inhibitor, improves cerebrovascular dysfunction is unknown. METHODS: OxHARP trial (Oxford Haemodynamic Adaptation to Reduce Pulsatility) was a double-blind, randomized, placebo-controlled, 3-way crossover trial after nonembolic cerebrovascular events with mild-moderate white matter hyperintensities (WMH), the most prevalent manifestation of cerebral small vessel disease. The primary outcome assessed the superiority of 3 weeks of sildenafil 50 mg thrice daily versus placebo (mixed-effect linear models) on middle cerebral artery pulsatility, derived from peak systolic and end-diastolic velocities (transcranial ultrasound), with noninferiority to cilostazol 100 mg twice daily. Secondary end points included the following: cerebrovascular reactivity during inhalation of air, 4% and 6% CO 2 on transcranial ultrasound (transcranial ultrasound-CVR); blood oxygen-level dependent–magnetic resonance imaging within WMH (CVR-WMH) and normal-appearing white matter (CVR-normal-appearing white matter); cerebral perfusion by arterial spin labeling (magnetic resonance imaging pseudocontinuous arterial spin labeling); and resistance by cerebrovascular conductance. Adverse effects were compared by Cochran Q. RESULTS: In 65/75 (87%) patients (median, 70 years;79% male) with valid primary outcome data, cerebral pulsatility was unchanged on sildenafil versus placebo (0.02, −0.01 to 0.05; P =0.18), or versus cilostazol (−0.01, −0.04 to 0.02; P =0.36), despite increased blood flow (∆ peak systolic velocity, 6.3 cm/s, 3.5–9.07; P <0.001; ∆ end-diastolic velocity, 1.98, 0.66–3.29; P =0.004). Secondary outcomes improved on sildenafil versus placebo for CVR-transcranial ultrasound (0.83 cm/s per mm Hg, 0.23–1.42; P =0.007), CVR-WMH (0.07, 0–0.14; P =0.043), CVR-normal-appearing white matter (0.06, 0.00–0.12; P =0.048), perfusion (WMH: 1.82 mL/100 g per minutes, 0.5–3.15; P =0.008; and normal-appearing white matter, 2.12, 0.66–3.6; P =0.006) and cerebrovascular resistance (sildenafil-placebo: 0.08, 0.05–0.10; P =4.9×10 −8 ; cilostazol-placebo, 0.06, 0.03–0.09; P =5.1×10 − 5 ). Both drugs increased headaches ( P =1.1×10 − 4 ), while cilostazol increased moderate-severe diarrhea ( P =0.013). CONCLUSIONS: Sildenafil did not reduce pulsatility but increased cerebrovascular reactivity and perfusion. Sildenafil merits further study to determine whether it prevents the clinical sequelae of small vessel disease. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03855332

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium

Background:Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. Methods:Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. Results:Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95 confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. Conclusion:Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2. © 2014 Cancer Research UK