Soft thermal contributions to 3-loop gauge coupling

We analyze 3-loop contributions to the gauge coupling felt by ultrasoft ("magnetostatic") modes in hot Yang-Mills theory. So-called soft/hard terms, originating from dimension-six operators within the soft effective theory, are shown to cancel 1097/1098 of the IR divergence found in a recent determination of the hard 3-loop contribution to the soft gauge coupling. The remaining 1/1098 originates from ultrasoft/hard contributions, induced by dimension-six operators in the ultrasoft effective theory. Soft 3-loop contributions are likewise computed, and are found to be IR divergent, rendering the ultrasoft gauge coupling non-perturbative at relative order O(alphas^{3/2}). We elaborate on the implications of these findings for effective theory studies of physical observables in thermal QCD.Comment: 31 pages. v2: clarifications added, published versio

Safety and efficacy of transarterial chemoembolization with degradable starch microspheres (DSM-TACE) in the treatment of secondary liver malignancies

Purpose: To evaluate the safety and efficacy of degradable starch microspheres (DSM) as embolic agents in transarterial chemoembolization (TACE) in the treatment of secondary liver metastases. Methods: This was a national, multicenter observational study. Primary endpoints were safety and treatment response according to Modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. Results: A total of 77 DSM-TACE procedures were performed in 20 patients. Minor immediate adverse events (AEs) were epigastric pain with an incidence of 45.5% (35/77), and nausea and vomiting at an incidence of 23.4% (18/77). Delayed minor AEs were epigastric pain in 13/77 (16.9%) treatments and nausea and vomiting in 10 (13.0%) treatments. No severe AEs were documented. Therapeutic efficacy of DSM-TACE procedures according to mRECIST was as follows: complete response 0/77, partial response 17/77, stable disease 33/77 and progressive disease 6/77, no data was available for 21/77 treatments. Overall, objective response was achieved in 8 of 20 patients (40.0%). Conclusion: DSM as embolic agent for TACE is safe in the treatment of liver metastases. An objective response in 40.0% of patients and disease control in 64.9% of procedures was achieved, and this should lead to further evaluation of DSM-TACE as treatment option for nonresectable liver metastases

On A Conjecture of Tian

We study Tian's $\alpha$-invariant in comparison with the $\alpha_1$-invariant for pairs $(S_d,H)$ consisting of a smooth surface $S_d$ of degree $d$ in the projective three-dimensional space and a hyperplane section $H$. A conjecture of Tian asserts that $\alpha(S_d,H)=\alpha_1(S_d,H)$. We show that this is indeed true for $d=4$ (the result is well known for $d\leqslant 3$), and we show that $\alpha(S_d,H)<\alpha_1(S_d,H)$ for $d\geqslant 8$ provided that $S_d$ is general enough. We also construct examples of $S_d$, for $d=6$ and $d=7$, for which Tian's conjecture fails. We provide a candidate counterexample for $S_5$.Comment: Final version. To appear in Mathematische Zeitschrif

Long-term survival after percutaneous irreversible electroporation of inoperable colorectal liver metastases

Background: For colorectal liver metastases (CRLM) that are not amenable to surgery or thermal ablation, irreversible electroporation (IRE) is a novel local treatment modality and additional option. Methods: This study is a retrospective long-term follow-up of patients with CRLM who underwent IRE as salvage treatment. Results: Of the 24 included patients, 18(75.0%) were male, and the median age was 57 (range: 28-75) years. The mean time elapsed from diagnosis to IRE was 37.9 +/- 37.3 months. Mean overall survival was 26.5 months after IRE (range: 2.5-69.2 months) and 58.1 months after diagnosis (range: 14.8-180.1 months). One-, three-, and five-year survival rates after initial diagnosis were 100.0%, 79.2%, and 41.2%; after IRE, the respective survival rates were 79.1%, 25.0%, and 8.3%. There were no statistically significant differences detected in survival after IRE with respect to gender, age, T- or N-stage at the time of diagnosis, size of metastases subject to IRE, number of hepatic lesions, or time elapsed between IRE and diagnosis. Conclusion: For nonresectable CRLM, long-term survival data emphasize the value of IRE as a new minimally invasive local therapeutic approach in multimodal palliative treatment, which is currently limited to systemic or regional therapies in this setting

Transarterial chemoembolization (TACE) with degradable starch microspheres (DSM) in hepatocellular carcinoma (HCC): multi-center results on safety and efficacy

Background: Hepatocellular carcinoma (HCC) is the 3rd leading cause of cancer-related death worldwide. The majority of HCCs are diagnosed in a stage that is not eligible for curative resection. For intermediate stage HCC, transarterial chemoembolization (TACE) is the recommended treatment. We evaluated the safety and efficacy of DSM (degradable starch microspheres) as embolic agent in transarterial chemoembolization (TACE) for the treatment of intermediate stage, non-resectable hepatocellular carcinoma (HCC). Methods and Findings: A national, multi-center observational study on the safety and efficacy of DSM-TACE for the treatment of intermediate HCC was conducted. The recruitment period for the study was from January 2010 to June 2014. The primary endpoints were safety and treatment response according to the mRECIST criteria. A total of 179 DSM-TACE procedures in 50 patients were included in the analysis. The therapeutic efficacy assessed with mRECIST was as follows: complete response (n=1; 2 %), 21 partial response (42 %), 13 stable disease (26 %), 9 progressive disease (18 %), and 6 incomplete data (12 %). Thus, the objective response rate was 44% (n=22) and disease control rate was 70% (n=35). A total of 76 immediate adverse events (AE) and 2 severe adverse events (SAE) were recorded. Forty-eight percent of patients (n=24) did not encounter any immediate AE/SAE. Between treatments, a total of 66 AE and one SAE were recorded. Twenty-four patients (48 %) did not encounter any AE/SAE in between treatments. Conclusion: The use of DSM as a TACE embolic agent appears to be safe for the treatment of HCC and has promising efficacy

Urine metabolome profiling of immune-mediated inflammatory diseases

Background: Immune-mediated inflammatory diseases (IMIDs) are a group of complex and prevalent diseases where disease diagnostic and activity monitoring is highly challenging. The determination of the metabolite profiles of biological samples is becoming a powerful approach to identify new biomarkers of clinical utility. In order to identify new metabolite biomarkers of diagnosis and disease activity, we have performed the first large-scale profiling of the urine metabolome of the six most prevalent IMIDs: rheumatoid arthritis, psoriatic arthritis, psoriasis, systemic lupus erythematosus, Crohn?s disease, and ulcerative colitis. Methods: Using nuclear magnetic resonance, we analyzed the urine metabolome in a discovery cohort of 1210 patients and 100 controls. Within each IMID, two patient subgroups were recruited representing extreme disease activity (very high vs. very low). Metabolite association analysis with disease diagnosis and disease activity was performed using multivariate linear regression in order to control for the effects of clinical, epidemiological, or technical variability. After multiple test correction, the most significant metabolite biomarkers were validated in an independent cohort of 1200 patients and 200 controls. Results: In the discovery cohort, we identified 28 significant associations between urine metabolite levels and disease diagnosis and three significant metabolite associations with disease activity (PFDR < 0.05). Using the validation cohort, we validated 26 of the diagnostic associations and all three metabolite associations with disease activity (PFDR < 0.05). Combining all diagnostic biomarkers using multivariate classifiers we obtained a good disease prediction accuracy in all IMIDs and particularly high in inflammatory bowel diseases. Several of the associated metabolites were found to be commonly altered in multiple IMIDs, some of which can be considered as hub biomarkers. The analysis of the metabolic reactions connecting the IMID-associated metabolites showed an overrepresentation of citric acid cycle, phenylalanine, and glycine-serine metabolism pathways. Conclusions: This study shows that urine is a source of biomarkers of clinical utility in IMIDs. We have found that IMIDs show similar metabolic changes, particularly between clinically similar diseases and we have found, for the first time, the presence of hub metabolites. These findings represent an important step in the development of more efficient and less invasive diagnostic and disease monitoring methods in IMIDs

Acid-evoked Ca2+ signalling in rat sensory neurones: effects of anoxia and aglycaemia

Ischaemia excites sensory neurones (generating pain) and promotes calcitonin gene-related peptide release from nerve endings. Acidosis is thought to play a key role in mediating excitation via the activation of proton-sensitive cation channels. In this study, we investigated the effects of acidosis upon Ca2+ signalling in sensory neurones from rat dorsal root ganglia. Both hypercapnic (pHo 6.8) and metabolic–hypercapnic (pHo 6.2) acidosis caused a biphasic increase in cytosolic calcium concentration ([Ca2+]i). This comprised a brief Ca2+ transient (half-time approximately 30 s) caused by Ca2+ influx followed by a sustained rise in [Ca2+]i due to Ca2+ release from caffeine and cyclopiazonic acid-sensitive internal stores. Acid-evoked Ca2+ influx was unaffected by voltage-gated Ca2+-channel inhibition with nickel and acid sensing ion channel (ASIC) inhibition with amiloride but was blocked by inhibition of transient receptor potential vanilloid receptors (TRPV1) with (E)-3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4] dioxin-6-yl)acrylamide (AMG 9810; 1 μM) and N-(4-tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl) tetrahydropryazine-1(2H)-carbox-amide (BCTC; 1 μM). Combining acidosis with anoxia and aglycaemia increased the amplitude of both phases of Ca2+ elevation and prolonged the Ca2+ transient. The Ca2+ transient evoked by combined acidosis, aglycaemia and anoxia was also substantially blocked by AMG 9810 and BCTC and, to a lesser extent, by amiloride. In summary, the principle mechanisms mediating increase in [Ca2+]i in response to acidosis are a brief Ca2+ influx through TRPV1 followed by sustained Ca2+ release from internal stores. These effects are potentiated by anoxia and aglycaemia, conditions also prevalent in ischaemia. The effects of anoxia and aglycaemia are suggested to be largely due to the inhibition of Ca2+-clearance mechanisms and possible increase in the role of ASICs