Cutaneous metastases in renal cell carcinoma: a case report

Renal cell carcinoma is the most common form of malignant renal tumour and is extremely lethal. About 25% of the patients develop metastasis at the time of diagnosis, and in many cases during the course of the disease, affecting the lung, lymphatic ganglions, liver, and bone, with skin metastases being quite rare

Deep Inelastic Scattering at the TeV Energy Scale and the LHeC Project

The prospect of an ep collider involving an LHC proton beam and a new electron accelerator is discussed. Configurations reaching centre of mass energies a factor of 5 beyond HERA are possible with luminosities of the order of 10^33 cm^-2 s^-1. The physics programme with such a facility is surveyed and possible machine and detector lay-outs are sketched.Comment: To appear in the proceedings of the Ringberg Workshop on New Trends in HERA Physics, October 200

Weekly paclitaxel, gemcitabine, and external irradiation followed by randomized farnesyl transferase inhibitor R115777 for locally advanced pancreatic cancer.

PURPOSE: The Radiation Therapy Oncology Group (RTOG) multi-institutional Phase II study 98-12, evaluating paclitaxel and concurrent radiation (RT) for locally advanced pancreatic cancer, demonstrated a median survival of 11.3 months and a 1-year survival of 43%. The purpose of the randomized Phase II study by RTOG 0020 was to evaluate the addition of weekly low- dose gemcitabine with concurrent paclitaxel/RT and to evaluate the efficacy and safety of the farnesyl transferase inhibitor R115777 following chemoradiation. PATIENTS AND METHODS: Patients with unresectable, nonmetastatic adenocarcinoma of the pancreas were eligible. Patients in Arm 1 received gemcitabine, 75 mg/m(2)/week, and paclitaxel, 40 mg/m(2)/week, for 6 weeks, with 50.4 Gy radiation (CXRT). Patients in Arm 2 received an identical chemoradiation regimen but then received maintenance R115777, 300 mg twice a day for 21 days every 28 days (CXRT+R115777), until disease progression or unacceptable toxicity. RESULTS: One hundred ninety-five patients were entered into this study, and 184 were analyzable. Grade 4 nonhematologic toxicities occurred in less than 5% of CXRT patients. The most common grade 3/4 toxicity from R115777 was myelosuppression; however, grade 3/4 hepatic, metabolic, musculoskeletal, and neurologic toxicities were also reported. The median survival time was 11.5 months and 8.9 months for the CXRT and CXRT+R115777 arms, respectively. CONCLUSIONS: The CXRT arm achieved a median survival of almost 1-year, supporting chemoradiation as an important therapeutic modality for locally advanced pancreatic cancer. Maintenance R115777 is not effective and is associated with a broad range of toxicities. These findings provide clinical evidence that inhibition of farnesylation affects many metabolic pathways, underscoring the challenge of developing an effective K-ras inhibitor

On the Universality of CP Violation in Delta F = 1 Processes

We show that new physics which breaks the left-handed SU(3)_Q quark flavor symmetry induces contributions to CP violation in Delta F = 1 couplings which are approximately universal, in that they are not affected by flavor rotations between the up and the down mass bases. (Only the short distance contributions are universal, while observables are also affected by hadronic matrix elements.) Therefore, such flavor violation cannot be aligned, and is constrained by the strongest bound from either the up or the down sectors. We use this result to show that the bound from eps'/eps prohibits an SU(3)_Q breaking explanation of the recent LHCb evidence for CP violation in D meson decays. Another consequence of this universality is that supersymmetric alignment models with a moderate mediation scale are consistent with the data, and are harder to probe via CP violating observables. With current constraints, therefore, squarks need not be degenerate. However, future improvements in the measurement of CP violation in D-Dbar mixing will start to probe alignment models.Comment: 10 pages, 2 figures. Clarifications and references adde

Machine detector interface for the e+e−e^+e^- future circular collider

The international Future Circular Collider (FCC) study aims at a design of $pp$, $e^+e^-$, $ep$ colliders to be built in a new 100 km tunnel in the Geneva region. The $e^+e^-$ collider (FCC-ee) has a centre of mass energy range between 90 (Z-pole) and 375 GeV (tt_bar). To reach such unprecedented energies and luminosities, the design of the interaction region is crucial. The crab-waist collision scheme has been chosen for the design and it will be compatible with all beam energies. In this paper we will describe the machine detector interface layout including the solenoid compensation scheme. We will describe how this layout fulfills all the requirements set by the parameters table and by the physical constraints. We will summarize the studies of the impact of the synchrotron radiation, the analysis of trapped modes and of the backgrounds induced by single beam and luminosity effects giving an estimate of the losses in the interaction region and in the detector.Comment: 6 pages, 7 figures, 62th ICFA ABDW on High Luminosity Circular $e^+e^-$ Colliders, eeFACT2018, Hong Kong, Chin

The precision electroweak data in warped extra-dimension models

The Randall-Sundrum scenario with Standard Model fields in the bulk and a custodial symmetry is considered. We determine the several minimal quark representations allowing to address the anomalies in the forward-backward b-quark asymmetry A^b_FB, while reproducing the bottom and top masses via wave function overlaps. The calculated corrections of the Zbb coupling include the combined effects of mixings with both Kaluza-Klein excitations of gauge bosons and new b'-like states. It is shown that the mechanism, in which the left-handed doublet of third generation quarks results from a mixing on the UV boundary of introduced fields Q_1L and Q_2L, is necessary for phenomenological reasons. Within the obtained models, both the global fit of R_b with A^b_FB [at the various center of mass energies] and the fit of last precision electroweak data in the light fermion sector can simultaneously be improved significantly with respect to the pure Standard Model case, for M_KK = 3,4,5 TeV (first KK gauge boson) and a best-fit Higgs mass m_h > 115 GeV i.e. compatible with the LEP2 direct limit. The quantitative analysis of the oblique parameters S,T,U even shows that heavy Higgs mass values up to ~500 GeV may still give rise to an acceptable quality of the electroweak data fit, in contrast with the Standard Model. The set of obtained constraints on the parameter space, derived partly from precision electroweak data, is complementary of a future direct exploration of this parameter space at the LHC. In particular, we find that custodians, like b' modes, can be as light as ~1200 GeV i.e. a mass lying possibly in the potential reach of LHC.Comment: 24 pages, 8 figures. Added references, corrected typos and Higgs mass dependence discussion complete

Overdetection, overtreatment and costs in prostate-specific antigen screening for prostate cancer

Background:Prostate cancer screening with prostate-specific antigen (PSA) has shown to reduce prostate cancer mortality in the European Randomised study of Screening for Prostate Cancer (ERSPC) trial. Overdetection and overtreatment are substantial unfavourable side effects with consequent healthcare costs. In this study the effects of introducing widespread PSA screening is evaluated.Methods:The MISCAN model was used to simulate prostate cancer growth and detection in a simulated cohort of 100 000 men (European standard population) over 25 years. PSA screening from age 55 to 70 or 75, with 1, 2 and 4-year-intervals is simulated. Number of diagnoses, PSA tests, biopsies, treatments, deaths and corresponding costs for 100 000 men and for United Kingdom and United States are compared.Results:Without screening 2378 men per 100 000 were predicted to be diagnosed with prostate cancer compared with 4956 men after screening at 4-year intervals. By introducing screening, the costs would increase with 100% to \[euro]60 695 000. Overdetection is related to 39% of total costs (\[euro]23 669 000). Screening until age 75 is relatively most expensive because of the costs of overtreatment.Conclusion:Introduction of PSA screening will increase total healthcare costs for prostate cancer substantially, of which the actual screening costs will be a small part

A Large Hadron Electron Collider at CERN

This document provides a brief overview of the recently published report on the design of the Large Hadron Electron Collider (LHeC), which comprises its physics programme, accelerator physics, technology and main detector concepts. The LHeC exploits and develops challenging, though principally existing, accelerator and detector technologies. This summary is complemented by brief illustrations of some of the highlights of the physics programme, which relies on a vastly extended kinematic range, luminosity and unprecedented precision in deep inelastic scattering. Illustrations are provided regarding high precision QCD, new physics (Higgs, SUSY) and electron-ion physics. The LHeC is designed to run synchronously with the LHC in the twenties and to achieve an integrated luminosity of O(100) fb$^{-1}$. It will become the cleanest high resolution microscope of mankind and will substantially extend as well as complement the investigation of the physics of the TeV energy scale, which has been enabled by the LHC

Dynamic Behavior of Salmonella-Induced Membrane Tubules in Epithelial Cells

Salmonella Typhimurium is a facultative intracellular pathogen that causes acute gastroenteritis in man. Intracellular Salmonella survive and replicate within a modified phagosome known as the Salmonella-containing vacuole (SCV). The onset of intracellular replication is accompanied by the appearance of membrane tubules, called Salmonella-induced filaments (Sifs), extending from the SCV. Sifs are enriched in late endosomal/lysosomal membrane proteins such as lysosome-associated membrane protein 1, but their formation and ability to interact with endosomal compartments are not characterized. In this study, we use live cell imaging techniques to define the dynamics of Sif formation in infected epithelial cells. At early time-points, Sifs are simple tubules extending from the surface of SCVs. These tubules are highly dynamic and exhibit bidirectional, microtubule-dependent movement. At the distal ends of individual Sif tubules, furthest from the SCV, a distinct ‘leader’ domain was often observed. At later times, Sifs develop into highly complex tubular networks that extend throughout the cell and appear less dynamic than nascent Sifs; however, individual tubules continue to display bidirectional dynamics. Sifs can acquire endocytic content by fusion, indicating a sustained interaction with the endocytic pathway. Together, these results show that these Salmonella-induced tubules form a highly dynamic network that involves both microtubule-dependent motility and interactions with endosomal compartments