Primordial black hole constraints in cosmologies with early matter domination

Moduli fields, a natural prediction of any supergravity and superstring-inspired supersymmetry theory, may lead to a prolonged period of matter domination in the early Universe. This can be observationally viable provided the moduli decay early enough to avoid harming nucleosynthesis. If primordial black holes form, they would be expected to do so before or during this matter dominated era. We examine the extent to which the standard primordial black hole constraints are weakened in such a cosmology. Permitted mass fractions of black holes at formation are of order $10^{-8}$, rather than the usual $10^{-20}$ or so. If the black holes form from density perturbations with a power-law spectrum, its spectral index is limited to $n \lesssim 1.3$, rather than the $n \lesssim 1.25$ obtained in the standard cosmology.Comment: 7 pages RevTeX file with four figures incorporated (uses RevTeX and epsf). Also available by e-mailing ARL, or by WWW at http://star-www.maps.susx.ac.uk/papers/infcos_papers.htm

Blue spectra and induced formation of primordial black holes

We investigate the statistical properties of primordial black hole (PBH) formation in the very early Universe. We show that the high level of inhomogeneity of the early Universe leads to the formation of the first generation PBHs. %The existence of these PBHs This causes later the appearance of a dust-like phase of the cosmological expansion. We discuss here a new mechanism for the second generation of PBH formation during the dust-like phase. This mechanism is based on the coagulation process. We demonstrate that the blue power spectrum of initial adiabatic perturbations after inflation leads to overproduction of primordial black holes with $10^9$g$\le M\le10^{15}$g if the power index is $n\ge1.2$.Comment: 16 pages, 2 figure

Supersymmetry and primordial black hole abundance constraints

We study the consequences of supersymmetry for primordial black hole (PBH) abundance constraints. PBHs with mass less than about 10^{11}g will emit supersymmetric particles when they evaporate. In most models of supersymmetry the lightest of these particles, the lightest supersymmetric particle (LSP), is stable and will hence survive to the present day. We calculate the limit on the initial abundance of PBHs from the requirement that the present day LSP density is less than the critical density. We apply this limit, along with those previously obtained from the effects of PBH evaporation on nucleosynthesis and the present day density of PBHs, to PBHs formed from the collpase of inflationary density perturbations, in the context of supersymmetric inflation models. If the reheat temperature after inflation is low, so as to avoid the overproduction of gravitinos and moduli, then the lightest PBHs which are produced in significant numbers will be evaporating around the present day and there are therefore no constraints from the effects of the evaporation products on nucleosynthesis or from the production of LSPs. We then examine models with a high reheat temperature and a subsequent period of thermal inflation. In these models avoiding the overproduction of LSPs limits the abundance of low mass PBHs which were previously unconstrained. Throughout we incorporate the production, at fixed time, of PBHs with a range of masses, which occurs when critical collapse is taken into account.Comment: 8 pages RevTeX file with 3 figures incorporated (uses RevTeX and epsf). Version to appear in Phys. Rev. D: minor change to calculation and added discussio

Cosmological constraints on primordial black holes produced in the near-critical gravitational collapse

The mass function of primordial black holes created through the near-critical gravitational collapse is calculated in a manner fairly independent of the statistical distribution of underlying density fluctuation, assuming that it has a sharp peak on a specific scale. Comparing it with various cosmological constraints on their mass spectrum, some newly excluded range is found in the volume fraction of the region collapsing into black holes as a function of the horizon mass.Comment: 9 pages. Typos corrected. To appear in Physical Review

Structure of the silicon vacancy in 6H-SiC after annealing identified as the carbon vacancy–carbon antisite pair

We investigated radiation-induced defects in neutron-irradiated and subsequently annealed 6H-silicon carbide (SiC) with electron paramagnetic resonance (EPR), the magnetic circular dichroism of the absorption (MCDA), and MCDA-detected EPR (MCDA-EPR). In samples annealed beyond the annealing temperature of the isolated silicon vacancy we observed photoinduced EPR spectra of spin S=1 centers that occur in orientations expected for nearest neighbor pair defects. EPR spectra of the defect on the three inequivalent lattice sites were resolved and attributed to optical transitions between photon energies of 999 and 1075 meV by MCDA-EPR. The resolved hyperfine structure indicates the presence of one single carbon nucleus and several silicon ligand nuclei. These experimental findings are interpreted with help of total energy and spin density data obtained from the standard local-spin density approximation of the density-functional theory, using relaxed defect geometries obtained from the self-consistent charge density-functional theory based tight binding scheme. We have checked several defect models of which only the photoexcited spin triplet state of the carbon antisite–carbon vacancy pair (CSi-VC) in the doubly positive charge state can explain all experimental findings. We propose that the (CSi-VC) defect is formed from the isolated silicon vacancy as an annealing product by the movement of a carbon neighbor into the vacancy

Recommendations for a practical implementation of circulating tumor DNA mutation testing in metastatic non-small-cell lung cancer

BACKGROUND: Liquid biopsy (LB) is a rapidly evolving diagnostic tool for precision oncology that has recently found its way into routine practice as an adjunct to tissue biopsy (TB). The concept of LB refers to any tumor-derived material, such as circulating tumor DNA (ctDNA) or circulating tumor cells that are detectable in blood. An LB is not limited to the blood and may include other fluids such as cerebrospinal fluid, pleural effusion, and urine, among others. PATIENTS AND METHODS: The objective of this paper, devised by international experts from various disciplines, is to review current challenges as well as state-of-the-art applications of ctDNA mutation testing in metastatic non-small-cell lung cancer (NSCLC). We consider pragmatic scenarios for the use of ctDNA from blood plasma to identify actionable targets for therapy selection in NSCLCs. RESULTS: Clinical scenarios where ctDNA mutation testing may be implemented in clinical practice include complementary tissue and LB testing to provide the full picture of patients’ actual predictive profiles to identify resistance mechanism (i.e. secondary mutations), and ctDNA mutation testing to assist when a patient has a discordant clinical history and is suspected of showing intertumor or intratumor heterogeneity. ctDNA mutation testing may provide interesting insights into possible targets that may have been missed on the TB. Complementary ctDNA LB testing also provides an option if the tumor location is hard to biopsy or if an insufficient sample was taken. These clinical use cases highlight practical scenarios where ctDNA LB may be considered as a complementary tool to TB analysis. CONCLUSIONS: Proper implementation of ctDNA LB testing in routine clinical practice is envisioned in the near future. As the clinical evidence of utility expands, the use of LB alongside tissue sample analysis may occur in the patient cases detailed here

Constraints on the density perturbation spectrum from primordial black holes

We re-examine the constraints on the density perturbation spectrum, including its spectral index $n$, from the production of primordial black holes. The standard cosmology, where the Universe is radiation dominated from the end of inflation up until the recent past, was studied by Carr, Gilbert and Lidsey; we correct two errors in their derivation and find a significantly stronger constraint than they did, $n \lesssim 1.25$ rather than their 1.5. We then consider an alternative cosmology in which a second period of inflation, known as thermal inflation and designed to solve additional relic over-density problems, occurs at a lower energy scale than the main inflationary period. In that case, the constraint weakens to $n \lesssim 1.3$, and thermal inflation also leads to a `missing mass' range, $10^{18} g \lesssim M \lesssim 10^{26} g$, in which primordial black holes cannot form. Finally, we discuss the effect of allowing for the expected non-gaussianity in the density perturbations predicted by Bullock and Primack, which can weaken the constraints further by up to 0.05.Comment: 10 pages RevTeX file with four figures incorporated (uses RevTeX and epsf). Also available by e-mailing ARL, or by WWW at http://star-www.maps.susx.ac.uk/papers/infcos_papers.htm

Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) overexpression in pancreatic ductal adenocarcinoma correlates with poor survival

<p>Abstract</p> <p>Background</p> <p>Pancreatic ductal adenocarcinoma is a lethal disease with a 5-year survival rate of 4% and typically presents in an advanced stage. In this setting, prognostic markers identifying the more agrressive tumors could aid in managment decisions. Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3, also known as IMP3 or KOC) is an oncofetal RNA-binding protein that regulates targets such as insulin-like growth factor-2 (IGF-2) and ACTB (beta-actin).</p> <p>Methods</p> <p>We evaluated the expression of IGF2BP3 by immunohistochemistry using a tissue microarray of 127 pancreatic ductal adenocarcinomas with tumor grade 1, 2 and 3 according to WHO criteria, and the prognostic value of IGF2BP3 expression.</p> <p>Results</p> <p>IGF2BP3 was found to be selectively overexpressed in pancreatic ductal adenocarcinoma tissues but not in benign pancreatic tissues. Nine (38%) patient samples of tumor grade 1 (n = 24) and 27 (44%) of tumor grade 2 (n = 61) showed expression of IGF2BP3. The highest rate of expression was seen in poorly differentiated specimen (grade 3, n = 42) with 26 (62%) positive samples. Overall survival was found to be significantly shorter in patients with IGF2BP3 expressing tumors (P = 0.024; RR 2.3, 95% CI 1.2-4.8).</p> <p>Conclusions</p> <p>Our data suggest that IGF2BP3 overexpression identifies a subset of pancreatic ductal adenocarcinomas with an extremely poor outcome and supports the rationale for developing therapies to target the IGF pathway in this cancer.</p