Properties and biases of the global heat flow compilation

Geothermal heat flow is inferred from the gradient of temperature values in boreholes or short-penetration probe measurements. Such measurements are expensive and logistically challenging in remote locations and, therefore, often targeted to regions of economic interest. As a result, measurements are not distributed evenly. Some tectonic, geologic and even topographic settings are overrepresented in global heat flow compilations; other settings are underrepresented or completely missing. These limitations in representation have implications for empirical heat flow models that use catalogue data to assign heat flow by the similarity of observables. In this contribution, we analyse the sampling bias in the Global Heat Flow database of the International Heat Flow Commission; the most recent and extensive heat flow catalogue, and discuss the implications for accurate prediction and global appraisals. We also suggest correction weights to reduce the bias when the catalogue is used for empirical modelling. From comparison with auxiliary variables, we find that each of the following settings is highly overrepresented for heat flow measurements; continental crust, sedimentary rocks, volcanic rocks, and Phanerozoic regions with hydrocarbon exploration. Oceanic crust, cratons, and metamorphic rocks are underrepresented. The findings also suggest a general tendency to measure heat flow in areas where the values are elevated; however, this conclusion depends on which auxiliary variable is under consideration to determine the settings. We anticipate that using our correction weights to balance disproportional representation will improve empirical heat flow models for remote regions and assist in the ongoing assessment of the Global Heat Flow database

New angles on top quark decay to a charged Higgs

To properly discover a charged Higgs Boson ($H^\pm$) requires its spin and couplings to be determined. We investigate how to utilize \ttbar spin correlations to analyze the $H^\pm$ couplings in the decay $t\to bH^+\to b\tau^+\nu_\tau$. Within the framework of a general Two-Higgs-Doublet Model, we obtain results on the spin analyzing coefficients for this decay and study in detail its spin phenomenology, focusing on the limits of large and small values for $\tan\beta$. Using a Monte Carlo approach to simulate full hadron-level events, we evaluate systematically how the $H^\pm\to\tau^\pm\nu_\tau$ decay mode can be used for spin analysis. The most promising observables are obtained from azimuthal angle correlations in the transverse rest frames of $t(\bar{t})$. This method is particularly useful for determining the coupling structure of $H^\pm$ in the large $\tan\beta$ limit, where differences from the SM are most significant.Comment: 28 pages, 13 figures. Uses JHEP forma

Intratumor Heterogeneity of the Estrogen Receptor and the Long-term Risk of Fatal Breast Cancer.

Background:Breast cancer patients with estrogen receptor (ER)-positive disease have a continuous long-term risk for fatal breast cancer, but the biological factors influencing this risk are unknown. We aimed to determine whether high intratumor heterogeneity of ER predicts an increased long-term risk (25 years) of fatal breast cancer. Methods:The STO-3 trial enrolled 1780 postmenopausal lymph node-negative breast cancer patients randomly assigned to receive adjuvant tamoxifen vs not. The fraction of cancer cells for each ER intensity level was scored by breast cancer pathologists, and intratumor heterogeneity of ER was calculated using Rao's quadratic entropy and categorized into high and low heterogeneity using a predefined cutoff at the second tertile (67%). Long-term breast cancer-specific survival analyses by intra-tumor heterogeneity of ER were performed using Kaplan-Meier and multivariable Cox proportional hazard modeling adjusting for patient and tumor characteristics. Results:A statistically significant difference in long-term survival by high vs low intratumor heterogeneity of ER was seen for all ER-positive patients (P < .001) and for patients with luminal A subtype tumors (P = .01). In multivariable analyses, patients with high intratumor heterogeneity of ER had a twofold increased long-term risk as compared with patients with low intratumor heterogeneity (ER-positive: hazard ratio [HR] = 1.98, 95% confidence interval [CI] = 1.31 to 3.00; luminal A subtype tumors: HR = 2.43, 95% CI = 1.18 to 4.99). Conclusions:Patients with high intratumor heterogeneity of ER had an increased long-term risk of fatal breast cancer. Interestingly, a similar long-term risk increase was seen in patients with luminal A subtype tumors. Our findings suggest that intratumor heterogeneity of ER is an independent long-term prognosticator with potential to change clinical management, especially for patients with luminal A tumors

Physics at the e+ e- Linear Collider

A comprehensive review of physics at an e+e- Linear Collider in the energy range of sqrt{s}=92 GeV--3 TeV is presented in view of recent and expected LHC results, experiments from low energy as well as astroparticle physics.The report focuses in particular on Higgs boson, Top quark and electroweak precision physics, but also discusses several models of beyond the Standard Model physics such as Supersymmetry, little Higgs models and extra gauge bosons. The connection to cosmology has been analyzed as well.Comment: 179 pages, plots and references updated, version to be published at EPJ

Prognostic implications of various models for calculation of S-phase fraction in 259 patients with soft tissue sarcoma

The S-phase fraction (SPF) in flow cytometric DNA histograms in soft tissue sarcoma (STS) can be calculated in various ways. The traditional planimetric method of Baisch has been shown to be prognostic, but is hampered by a failure rate of around 40%. We therefore tested other models to see if this rate could be decreased with retained prognostic value. In 259 STS of the locomotor system the SPF was calculated according to Baisch and with commercial parametric MultiCycle software using different corrections for background. Using the Baisch model, 159 histograms could be evaluated for SPF. The 5-year metastasis-free survival rate (MFSR) was 0.94 for the low-risk group (defined with SPF), and 0.53 for the high-risk group. In the low-risk group, four of the seven patients who developed metastasis did so after 5 years. Using the MultiCycle software, SPF could be calculated in 253 tumours. Depending on type of background correction used, the 5-year MFSR varied between 0.67 and 0.82 for the low-risk group, and between 0.47 and 0.53 for the high-risk group. The late metastasis pattern in the low-risk group was never seen using the MultiCycle software. We conclude that in paraffin archival material, calculation of SPF according to Baisch is preferable in clinical use due to better separation between low-risk and high-risk groups, and also the possibility to identify patients who metastasize late. © 1999 Cancer Research Campaig

Pharmacogenetics of efficiency and tolerance of the peroral antidiabetic drug metformin

Elektroniskā versija nesatur pielikumusMetformīns ir pirmās izvēles medikaments jaundiagnosticētu 2.tipa cukura diabēta (T2DM) pacientu ārstēšanā. Mēs identificējām asociāciju starp metformīna blakusparādībām un 2 ģenētiskiem variantiem (rs628031 and rs36056065) Organisko Katjonu transportierī 1 (OCT1/SLC22A1). Polimorfismiem rs3119309, rs2481030 un rs7757336, lokalizētiem Organisko Katjonu transportieru 2 un 3 (OCT2/SLC22A2 un OCT3/SLC22A3) starpgēnu reģionā, tika noteikta būtiska asociācija ar metformīna īstermiņa terapijas efektivitāti. Divi no šiem variantiem tika analizēti replikācijas pētījumā ar 126 T2DM pacientiem no Slovākijas un farmakokinētikas pētījumā ar 15 veseliem brīvprātīgajiem. Visbeidzot, 33 ģenētiskas variācijas tika izpētītas ATM, STK11 un T2DM kandidātgēnos, bet tikai dažas no tām bija nomināli asociētas ar metformīna īstermiņa terapijas efektivitāti. Atslēgas vārdi: OCTs, metformīns, farmakoģenētika, blakusparādības, efektivitāte.Metformin is the first-line medication used in treatment of newly-diagnosticed Type 2 diabetes mellitus (T2DM). We show an association between metformin side-effects and two genetic variants (rs628031 and rs36056065) in Organic Cation Transporter 1 (OCT1/SLC22A1). Polymorphisms rs3119309, rs2481030 un rs7757336 in intergenic region between Organic Cation Transporter 2 and 3 (OCT2/SLC22A2 and OCT3/ SLC22A3) were found to be associated with short-term efficiency of metformin therapy. Two of these variants were analysed in replication study in 126 T2DM patients from Slovakia and in pharmacokinetic study with 15 healthy participants. At last, 33 genetic variants in ATM, STK11 and list of T2DM susceptibility genes were investigated, but only few showed a nominal association with short-term efficiency of metformin monotherapy. Keywords: OCTs, metformin, pharmacogenetics, side-effects, efficiency