Electronic Raman scattering of Tl-2223 and the symmetry of the supercon- ducting gap

Single crystalline Tl2Ba2Ca2Cu3O10 was studied using electronic Raman scattering. The renormalization of the scattering continuum was investigated as a function of the scattering geometry to determine the superconducting energy gap 2Delta(k). The A1g- and B2g-symmetry component show a linear frequency behaviour of the scattering intensity with a peak related to the energy gap, while the B1g-symmetry component shows a characteristic behaviour at higher frequencies. The observed frequency dependencies are consistent with a dx^2-y^2-wave symmetry of the gap and yield a ratio of 2Delta/k_BT_c=7.4. With the polarization of the scattered and incident light either parallel or perpendicular to the CuO2-planes a strong anisotropy due to the layered structure was detected, which indicates an almost 2 dimensional behaviour of this system.Comment: 2 pages, Postscript-file including 2 figures. Accepted for publication in the Proceedings of the M^2SHTSC IV Conference, Grenoble (France), 5-9 July 1994. Proceedings to be published in Physica C. Contact address: [email protected]

Analytic structure of solutions to multiconfiguration equations

We study the regularity at the positions of the (fixed) nuclei of solutions to (non-relativistic) multiconfiguration equations (including Hartree--Fock) of Coulomb systems. We prove the following: Let {phi_1,...,phi_M} be any solution to the rank--M multiconfiguration equations for a molecule with L fixed nuclei at R_1,...,R_L in R^3. Then, for any j in {1,...,M} and k in {1,...,L}, there exists a neighbourhood U_{j,k} in R^3 of R_k, and functions phi^{(1)}_{j,k}, phi^{(2)}_{j,k}, real analytic in U_{j,k}, such that phi_j(x) = phi^{(1)}_{j,k}(x) + |x - R_k| phi^{(2)}_{j,k}(x), x in U_{j,k} A similar result holds for the corresponding electron density. The proof uses the Kustaanheimo--Stiefel transformation, as applied earlier by the authors to the study of the eigenfunctions of the Schr"odinger operator of atoms and molecules near two-particle coalescence points.Comment: 15 page

A large multi-ethnic genome-wide association study identifies novel genetic loci for intraocular pressure.

Elevated intraocular pressure (IOP) is a major risk factor for glaucoma, a leading cause of blindness. IOP heritability has been estimated to up to 67%, and to date only 11 IOP loci have been reported, accounting for 1.5% of IOP variability. Here, we conduct a genome-wide association study of IOP in 69,756 untreated individuals of European, Latino, Asian, and African ancestry. Multiple longitudinal IOP measurements were collected through electronic health records and, in total, 356,987 measurements were included. We identify 47 genome-wide significant IOP-associated loci (P < 5 × 10-8); of the 40 novel loci, 14 replicate at Bonferroni significance in an external genome-wide association study analysis of 37,930 individuals of European and Asian descent. We further examine their effect on the risk of glaucoma within our discovery sample. Using longitudinal IOP measurements from electronic health records improves our power to identify new variants, which together explain 3.7% of IOP variation

The impact of adjusting for baseline in pharmacogenomic genome-wide association studies of quantitative change.

In pharmacogenomic studies of quantitative change, any association between genetic variants and the pretreatment (baseline) measurement can bias the estimate of effect between those variants and drug response. A putative solution is to adjust for baseline. We conducted a series of genome-wide association studies (GWASs) for low-density lipoprotein cholesterol (LDL-C) response to statin therapy in 34,874 participants of the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort as a case study to investigate the impact of baseline adjustment on results generated from pharmacogenomic studies of quantitative change. Across phenotypes of statin-induced LDL-C change, baseline adjustment identified variants from six loci meeting genome-wide significance (SORT/CELSR2/PSRC1, LPA, SLCO1B1, APOE, APOB, and SMARCA4/LDLR). In contrast, baseline-unadjusted analyses yielded variants from three loci meeting the criteria for genome-wide significance (LPA, APOE, and SLCO1B1). A genome-wide heterogeneity test of baseline versus statin on-treatment LDL-C levels was performed as the definitive test for the true effect of genetic variants on statin-induced LDL-C change. These findings were generally consistent with the models not adjusting for baseline signifying that genome-wide significant hits generated only from baseline-adjusted analyses (SORT/CELSR2/PSRC1, APOB, SMARCA4/LDLR) were likely biased. We then comprehensively reviewed published GWASs of drug-induced quantitative change and discovered that more than half (59%) inappropriately adjusted for baseline. Altogether, we demonstrate that (1) baseline adjustment introduces bias in pharmacogenomic studies of quantitative change and (2) this erroneous methodology is highly prevalent. We conclude that it is critical to avoid this common statistical approach in future pharmacogenomic studies of quantitative change

How should the respiration rate be counted in cattle?

Respiration rate (RR) is a proficient indicator to measure the health status of cattle. The common method of measurement is to count the number of respiratory cycles each minute based on flank movements. However, there is no consistent method of execution. In previous studies, various methods have been described, including counting flank movements for 15 s, 30 s or 60 s as well as stopping the time for 5 or 10 breaths. We assume that the accuracy of the aforementioned methods differs. Therefore, we compared their precision with an RR sensor, which was used as the reference method in this study. Five scientists from the fields of agricultural science and veterinary medicine quantified the flank movement according to each of the five methods mentioned above. The results showed that with an average RR of 30 breaths per minute (bpm), all methods showed a high correlation to the values of the RR sensor. However, counting breaths for 60 s had the highest level of conformity with the RR sensor (Lin`s concordance correlation coefficient: 0.96) regardless of the level of RR. With rising RR, the inaccuracy increased significantly for the other four investigated methods, especially when counting 5 and 10 breaths. Therefore, we would recommend that counting for 60 s should be used as the standard method for future studies due to its high precision regardless of the level of RR

Novel treatment options in head and neck cancer

The treatment of head and neck squamous cell carcinoma (HNSCC) has been a medical challenge with limited improvement in overall survival over the past few decades. However, recently, very interesting innovations in the field of immunotherapy have been shown to be beneficial for patients with advanced HNSCC. In this article, the latest medical developments are reviewed with special focus on the clinical achievements and current clinical studies in the field of immunotherapy. The landscape of clinical studies has changed considerably from antibody-based growth factor inhibition towards immune checkpoint modulation, and new indications in the adjuvant and neoadjuvant setting are being tested in large patient cohorts. Even the combination of 2 or more immune modulatory approaches and the correct synchronization with standard cancer therapy is promising and warrants suitable clinical trials

a meta-analysis of the 5-year efficacy and safety

Background The objective of this study was to compare the efficacy and safety of taxane (docetaxel or paclitaxel), cisplatin, and fluorouracil (Tax-PF) with cisplatin plus fluorouracil (PF) regimen by a meta-analysis of data retrieved from the literature. Methods Seven randomized clinical trials were identified, which included patients with advanced head and neck cancer who underwent induction chemotherapy with either a Tax-PF or PF protocol. The outcomes included the 3-year and 5-year overall survival (OS) and progression-free survival (PFS), overall response rate (ORR) and different types of adverse events. Results The 3-year OS rate (HR: 1.14; 95% CI: 1.03 to 1.25; P = 0.008), 3-year PFS rate (HR: 1.24; 95% CI: 1.08 to 1.43; P = 0.002), 5-year OS rate (HR: 1.30; 95% CI, 1.09 to 1.55;P = 0.003), 5-year PFS rate (HR: 1.39; 95% CI, 1.14 to 1.70; P = 0.001) and ORR to chemotherapy (OR 1.66; 95% CI, 1.35 to 2.05; P < 0.001) of the patients in the Tax-PF group were statistically superior to those in the PF group. In terms of toxicities, the incidence of febrile neutropenia (OR 2.36; 95% CI, 1.62 to 3.46; P < 0.001), alopecia (OR 8.22; 95% CI, 3.99 to 16.92; P < 0.001), diarrhea (OR 1.57; 95% CI, 1.05 to 2.36; P = 0.03) and leukopenia (OR 2.79; 95% CI, 1.86 to 4.21; P < 0.001) was higher in the Tax-PF group. Conclusion The Tax-PF induction chemotherapy improved PFS and OS, and the ORR was better as compared to PF- based therapy regimens at the cost of a higher incidence of adverse events

Genetic variation in the SIM1 locus is associated with erectile dysfunction.

Erectile dysfunction affects millions of men worldwide. Twin studies support the role of genetic risk factors underlying erectile dysfunction, but no specific genetic variants have been identified. We conducted a large-scale genome-wide association study of erectile dysfunction in 36,649 men in the multiethnic Kaiser Permanente Northern California Genetic Epidemiology Research in Adult Health and Aging cohort. We also undertook replication analyses in 222,358 men from the UK Biobank. In the discovery cohort, we identified a single locus (rs17185536-T) on chromosome 6 near the single-minded family basic helix-loop-helix transcription factor 1 (SIM1) gene that was significantly associated with the risk of erectile dysfunction (odds ratio = 1.26, P = 3.4 × 10-25). The association replicated in the UK Biobank sample (odds ratio = 1.25, P = 6.8 × 10-14), and the effect is independent of known erectile dysfunction risk factors, including body mass index (BMI). The risk locus resides on the same topologically associating domain as SIM1 and interacts with the SIM1 promoter, and the rs17185536-T risk allele showed differential enhancer activity. SIM1 is part of the leptin-melanocortin system, which has an established role in body weight homeostasis and sexual function. Because the variants associated with erectile dysfunction are not associated with differences in BMI, our findings suggest a mechanism that is specific to sexual function