The failure of stellar feedback, magnetic fields, conduction, and morphological quenching in maintaining red galaxies

The quenching "maintenance'" and related "cooling flow" problems are important in galaxies from Milky Way mass through clusters. We investigate this in halos with masses $\sim 10^{12}-10^{14}\,{\rm M}_{\odot}$, using non-cosmological high-resolution hydrodynamic simulations with the FIRE-2 (Feedback In Realistic Environments) stellar feedback model. We specifically focus on physics present without AGN, and show that various proposed "non-AGN" solution mechanisms in the literature, including Type Ia supernovae, shocked AGB winds, other forms of stellar feedback (e.g. cosmic rays), magnetic fields, Spitzer-Braginskii conduction, or "morphological quenching" do not halt or substantially reduce cooling flows nor maintain "quenched" galaxies in this mass range. We show that stellar feedback (including cosmic rays from SNe) alters the balance of cold/warm gas and the rate at which the cooled gas within the galaxy turns into stars, but not the net baryonic inflow. If anything, outflowing metals and dense gas promote additional cooling. Conduction is important only in the most massive halos, as expected, but even at $\sim 10^{14}\,{\rm M}_{\odot}$ reduces inflow only by a factor $\sim 2$ (owing to saturation effects and anisotropic suppression). Changing the morphology of the galaxies only slightly alters their Toomre-$Q$ parameter, and has no effect on cooling (as expected), so has essentially no effect on cooling flows or maintaining quenching. This all supports the idea that additional physics, e.g., AGN feedback, must be important in massive galaxies.Comment: 16 pages, 12 figure

Cosmic Rays or Turbulence can Suppress Cooling Flows (Where Thermal Heating or Momentum Injection Fail)

The quenching ‘maintenance’ and ‘cooling flow’ problems are important from the Milky Way through massive cluster elliptical galaxies. Previous work has shown that some source of energy beyond that from stars and pure magnetohydrodynamic processes is required, perhaps from active galactic nuclei, but even the qualitative form of this energetic input remains uncertain. Different scenarios include thermal ‘heating’, direct wind or momentum injection, cosmic ray heating or pressure support, or turbulent ‘stirring’ of the intracluster medium (ICM). We investigate these in 10¹²−10¹⁴M⊙ haloes using high-resolution non-cosmological simulations with the FIRE-2 (Feedback In Realistic Environments) stellar feedback model, including simplified toy energy injection models, where we arbitrarily vary the strength, injection scale, and physical form of the energy. We explore which scenarios can quench without violating observational constraints on energetics or ICM gas. We show that turbulent stirring in the central ∼100 kpc, or cosmic ray injection, can both maintain a stable low-star formation rate halo for >Gyr time-scales with modest energy input, by providing a non-thermal pressure that stably lowers the core density and cooling rates. In both cases, associated thermal-heating processes are negligible. Turbulent stirring preserves cool-core features while mixing condensed core gas into the hotter halo and is by far the most energy efficient model. Pure thermal heating or nuclear isotropic momentum injection require vastly larger energy, are less efficient in lower mass haloes, easily overheat cores, and require fine tuning to avoid driving unphysical temperature gradients or gas expulsion from the halo centre

Cosmic Rays or Turbulence can Suppress Cooling Flows (Where Thermal Heating or Momentum Injection Fail)

The quenching ‘maintenance’ and ‘cooling flow’ problems are important from the Milky Way through massive cluster elliptical galaxies. Previous work has shown that some source of energy beyond that from stars and pure magnetohydrodynamic processes is required, perhaps from active galactic nuclei, but even the qualitative form of this energetic input remains uncertain. Different scenarios include thermal ‘heating’, direct wind or momentum injection, cosmic ray heating or pressure support, or turbulent ‘stirring’ of the intracluster medium (ICM). We investigate these in 10¹²−10¹⁴M⊙ haloes using high-resolution non-cosmological simulations with the FIRE-2 (Feedback In Realistic Environments) stellar feedback model, including simplified toy energy injection models, where we arbitrarily vary the strength, injection scale, and physical form of the energy. We explore which scenarios can quench without violating observational constraints on energetics or ICM gas. We show that turbulent stirring in the central ∼100 kpc, or cosmic ray injection, can both maintain a stable low-star formation rate halo for >Gyr time-scales with modest energy input, by providing a non-thermal pressure that stably lowers the core density and cooling rates. In both cases, associated thermal-heating processes are negligible. Turbulent stirring preserves cool-core features while mixing condensed core gas into the hotter halo and is by far the most energy efficient model. Pure thermal heating or nuclear isotropic momentum injection require vastly larger energy, are less efficient in lower mass haloes, easily overheat cores, and require fine tuning to avoid driving unphysical temperature gradients or gas expulsion from the halo centre

Family history of cancer and risk for esophageal and gastric cancer in Shanxi, China

<p>Abstract</p> <p>Background</p> <p>Family history (FH) by different relative types and risk of upper gastrointestinal (UGI) cancers has been only rarely reported; the data on UGI cancer survival are sparse.</p> <p>Methods</p> <p>600 esophageal squamous cell carcinoma (ESCC) cases, 598 gastric cardia adenocarcinoma cases, and 316 gastric non-cardia adenocarcinoma cases, and 1514 age-, gender-, and neighborhood-matched controls were asked for FH in first degree relatives and non-blood relatives. Odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regressions, and hazard ratios (HRs) from Cox proportional hazard regressions were estimated.</p> <p>Results</p> <p>Increased ESCC risk was associated with FH of any cancer (OR = 1.72, 95% CI = 1.39–2.12), FH of any UGI cancer (OR = 2.28, 95%CI = 1.77–2.95) and FH of esophageal cancer (OR = 2.84, 95%CI = 2.09–3.86), but not FH of non-UGI cancer. Individuals with two or more affected first-degree relatives had 10-fold increased ESCC risk. FH of gastric cardia cancer was associated with an increased risk of all three cancers. Cancer in non-blood relatives was not associated with risk of any UGI cancer. FH of UGI cancer was associated with a poorer survival rate among younger ESCC cases (HR = 1.82, 95%CI = 1.01–3.29).</p> <p>Conclusion</p> <p>These data provide strong evidence that shared susceptibility is involved in esophageal carcinogenesis and also suggest a role in prognosis.</p

Involvement of the Efflux Pumps in Chloramphenicol Selected Strains of Burkholderia thailandensis: Proteomic and Mechanistic Evidence

Burkholderia is a bacterial genus comprising several pathogenic species, including two species highly pathogenic for humans, B. pseudomallei and B. mallei. B. thailandensis is a weakly pathogenic species closely related to both B. pseudomallei and B. mallei. It is used as a study model. These bacteria are able to exhibit multiple resistance mechanisms towards various families of antibiotics. By sequentially plating B. thailandensis wild type strains on chloramphenicol we obtained several resistant variants. This chloramphenicol-induced resistance was associated with resistance against structurally unrelated antibiotics including quinolones and tetracyclines. We functionally and proteomically demonstrate that this multidrug resistance phenotype, identified in chloramphenicol-resistant variants, is associated with the overexpression of two different efflux pumps. These efflux pumps are able to expel antibiotics from several families, including chloramphenicol, quinolones, tetracyclines, trimethoprim and some β-lactams, and present a partial susceptibility to efflux pump inhibitors. It is thus possible that Burkholderia species can develop such adaptive resistance mechanisms in response to antibiotic pressure resulting in emergence of multidrug resistant strains. Antibiotics known to easily induce overexpression of these efflux pumps should be used with discernment in the treatment of Burkholderia infections

Postmenopausal Hormone Therapy and Colorectal Cancer Risk by Molecularly Defined Subtypes and Tumor Location

Background: Postmenopausal hormone therapy (HT) is associated with a decreased colorectal cancer (CRC) risk. As CRC is a heterogeneous disease, we evaluated whether the association of HT and CRC differs across etiologically relevant, molecularly defined tumor subtypes and tumor location. Methods: We pooled data on tumor subtypes (microsatellite instability status, CpG island methylator phenotype status, BRAF and KRAS mutations, pathway: adenoma-carcinoma, alternate, serrated), tumor location (proximal colon, distal colon, rectum), and HT use among 8220 postmenopausal women (3898 CRC cases and 4322 controls) from 8 observational studies. We used multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CIs) for the association of ever vs never HT use with each tumor subtype compared with controls. Models were adjusted for study, age, body mass index, smoking status, and CRC family history. All statistical tests were 2-sided. Results: Among postmenopausal women, ever HT use was associated with a 38% reduction in overall CRC risk (OR =0.62, 95% CI = 0.56 to 0.69). This association was similar according to microsatellite instability, CpG island methylator phenotype and BRAF or KRAS status. However, the association was attenuated for tumors arising through the serrated pathway (OR = 0.81, 95% CI = 0.66 to 1.01) compared with the adenoma-carcinoma pathway (OR = 0.63, 95% CI = 0.55 to 0.73; P het =.04) and alternate pathway (OR = 0.61, 95% CI = 0.51 to 0.72). Additionally, proximal colon tumors had a weaker association (OR = 0.71, 95% CI = 0.62 to 0.80) compared with rectal (OR = 0.54, 95% CI = 0.46 to 0.63) and distal colon (OR = 0.57, 95% CI = 0.49 to 0.66; P het =.01) tumors. Conclusions: We observed a strong inverse association between HT use and overall CRC risk, which may predominantly reflect a benefit of HT use for tumors arising through the adenoma-carcinoma and alternate pathways as well as distal colon and rectal tumors

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A&gt;T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations