mTORC2 signaling drives the development and progression of pancreatic cancer

mTOR signaling controls several critical cellular functions and is deregulated in many cancers, including pancreatic cancer. To date, most efforts have focused on inhibiting the mTORC1 complex. However, clinical trials of mTORC1 inhibitors in pancreatic cancer have failed, raising questions about this therapeutic approach. We employed a genetic approach to delete the obligate mTORC2 subunit Rictor and identified the critical times during which tumorigenesis requires mTORC2 signaling. Rictor deletion resulted in profoundly delayed tumorigenesis. Whereas previous studies showed most pancreatic tumors were insensitive to rapamycin, treatment with a dual mTORC1/2 inhibitor strongly suppressed tumorigenesis. In late-stage tumor-bearing mice, combined mTORC1/2 and PI3K inhibition significantly increased survival. Thus, targeting mTOR may be a potential therapeutic strategy in pancreatic cancer

Softening the Supersymmetric Flavor Problem in Orbifold GUTs

The infra-red attractive force of the bulk gauge interactions is applied to soften the supersymmetric flavor problem in the orbifold SU(5) GUT of Kawamura. Then this force aligns in the infra-red regime the soft supersymmetry breaking terms out of their anarchical disorder at a fundamental scale, in such a way that flavor-changing neutral currents as well as dangerous CP-violating phases are suppressed at low energies. It is found that this dynamical alignment is sufficiently good compared with the current experimental bounds, as long as the diagonalization matrices of the Yukawa couplings are CKM-like.Comment: 15 pages,4 figure

Implementation of routine outcome measurement in child and adolescent mental health services in the United Kingdom: a critical perspective

The aim of this commentary is to provide an overview of clinical outcome measures that are currently recommended for use in UK Child and Adolescent Mental Health Services (CAMHS), focusing on measures that are applicable across a wide range of conditions with established validity and reliability, or innovative in their design. We also provide an overview of the barriers and drivers to the use of Routine Outcome Measurement (ROM) in clinical practice

A randomised, feasibility trial of an Exercise and Nutrition-based Rehabilitation programme (ENeRgy) in people with cancer

From Wiley via Jisc Publications RouterErna Haraldsdottir - ORCID: 0000-0003-4891-0743 https://orcid.org/0000-0003-4891-0743Background: Despite rehabilitation being increasingly advocated for people living with incurable cancer, there is limited evidence supporting efficacy or component parts. The progressive decline in function and nutritional in this population would support an approach that targets these factors. This trial aimed to assess the feasibility of an exercise and nutrition based rehabilitation programme in people with incurable cancer. Methods: We randomized community dwelling adults with incurable cancer to either a personalized exercise and nutrition based programme (experimental arm) or standard care (control arm) for 8 weeks. Endpoints included feasibility, quality of life, physical activity (step count), and body weight. Qualitative and health economic analyses were also included. Results: Forty‐five patients were recruited (23 experimental arm, 22 control arm). There were 26 men (58%), and the median age was 78 years (IQR 69–84). At baseline, the median BMI was 26 kg/m2 (IQR: 22–29), and median weight loss in the previous 6 months was 5% (IQR: −12% to 0%). Adherence to the experimental arm was >80% in 16/21 (76%) patients. There was no statistically significant difference in the following between trial arms: step count − median % change from baseline to endpoint, per trial arm (experimental −18.5% [IQR: −61 to 65], control 5% [IQR: −32 to 50], P = 0.548); weight − median % change from baseline to endpoint, per trial arm (experimental 1%[IQR: −3 to 3], control −0.5% [IQR: −3 to 1], P = 0.184); overall quality of life − median % change from baseline to endpoint, per trial arm (experimental 0% [IQR: −20 to 19], control 0% [IQR: −23 to 33], P = 0.846). Qualitative findings observed themes of capability, opportunity, and motivation amongst patients in the experimental arm. The mean incremental cost of the experimental arm versus control was £‐319.51 [CI −7593.53 to 6581.91], suggesting the experimental arm was less costly. Conclusions: An exercise and nutritional rehabilitation intervention is feasible and has potential benefits for people with incurable cancer. A larger trial is now warranted to test the efficacy of this approach.12pubpub

Geographically touring the eastern bloc: British geography, travel cultures and the Cold War

This paper considers the role of travel in the generation of geographical knowledge of the eastern bloc by British geographers. Based on oral history and surveys of published work, the paper examines the roles of three kinds of travel experience: individual private travels, tours via state tourist agencies, and tours by academic delegations. Examples are drawn from across the eastern bloc, including the USSR, Poland, Romania, East Germany and Albania. The relationship between travel and publication is addressed, notably within textbooks, and in the Geographical Magazine. The study argues for the extension of accounts of cultures of geographical travel, and seeks to supplement the existing historiography of Cold War geography

A survey for redshifted molecular and atomic absorption lines I

We are currently undertaking a large survey for redshifted atomic and molecular absorption ... only one clear and one tentative detection were obtained: HI absorption at z = 0.097 in PKS 1555-140 and OH absorption at z =0.126 in PKS 2300-189, respectively... In order to determine why no clear molecular absorption was detected in any of the 13 sources searched, we investigate the properties of the five redshifted systems currently known to exhibit OH absorption. In four of these, molecules were first detected via millimetre-wave transitions and the flat radio spectra indicate compact background continuum sources, which may suggest a high degree of coverage of the background source by the molecular clouds in the absorber. Furthermore, for these systems we find a relationship between the molecular line strength and red optical--near infrared (V-K) colours, thus supporting the notion that the reddening of these sources is due to dust, which provides an environment conducive to the formation of molecules. Upon comparison with the V-K colours of our sample, this relationship suggests that, presuming the reddening occurs at the host galaxy redshift at least in some of the targets, many of our observations still fall short of the sensitivityrequired to detect OH absorption, although a confirmation of the ``detection'' of OH in 2300-189 could contravene this.Comment: 13 pages, loads of figures, accepted by MNRA

Joint 3D modelling of the polarized Galactic synchrotron and thermal dust foreground diffuse emission

We present for the first time a coherent model of the polarized Galactic synchrotron and thermal dust emissions which are the main diffuse foreground for the measurement of the polarized power spectra of the CMB fluctuations with the Planck satellite mission. We produce 3D models of the Galactic magnetic field including regular and turbulent components, and of the distribution of matter in the Galaxy, relativistic electrons and dust grains. By integrating along the line of sight we construct maps of the polarized Galactic synchrotron and thermal dust emission for each of these models and compare them to currently available data. We consider the 408 MHz all-sky continuum survey, the 23 GHz band of the Wilkinson Microwave Anisotropy Probe and the 353 GHz Archeops data.}{The best-fit parameters obtained are consistent with previous estimates in the literature based only on synchrotron emission and pulsar rotation measurements. They allows us to reproduce the large scale structures observed on the data. Poorly understood local Galactic structures and turbulence make difficult an accurate reconstruction of the observations in the Galactic plane. Finally, using the best-fit model we are able to estimate the expected polarized foreground contamination at the Planck frequency bands. For the CMB bands, 70, 100, 143 and 217 GHz, at high Galactic latitudes although the CMB signal dominates in general, a significant foreground contribution is expected at large angular scales. In particular, this contribution will dominate the CMB signal for the B modes expected from realistic models of a background of primordial gravitational waves

Muon anomalous magnetic moment, lepton flavor violation, and flavor changing neutral current processes in SUSY GUT with right-handed neutrino

Motivated by the large mixing angle solutions for the atmospheric and solar neutrino anomalies, flavor changing neutral current processes and lepton flavor violating processes as well as the muon anomalous magnetic moment are analyzed in the framework of SU(5) SUSY GUT with right-handed neutrino. In order to explain realistic mass relations for quarks and leptons, we take into account effects of higher dimensional operators above the GUT scale. It is shown that the supersymmetric (SUSY) contributions to the CP violation parameter in $K^0-\bar{K}^0$ mixing, $\epsilon_K$, the $\mu \to e \gamma$ branching ratio, and the muon anomalous magnetic moment become large in a wide range of parameter space. We also investigate correlations among these quantities. Within the current experimental bound of $\text{B}(\mu \to e \gamma)$, large SUSY contributions are possible either in the muon anomalous magnetic moment or in $\epsilon_K$. In the former case, the favorable value of the recent muon anomalous magnetic moment measurement at the BNL E821 experiment can be accommodated. In the latter case, the allowed region of the Kobayashi-Maskawa phase can be different from the prediction within the Standard Model (SM) and therefore the measurements of the CP asymmetry of $B\to J/\psi K_S$ mode and $\Delta m_{B_s}$ could discriminate this case from the SM. We also show that the $\tau \to \mu \gamma$ branching ratio can be close to the current experimental upperbound and the mixing induced CP asymmetry of the radiative B decay can be enhanced in the case where the neutrino parameters correspond to the Mikheyev-Smirnov-Wolfenstein small mixing angle solution.Comment: 70 pages, 14 figure

Liquid 4He near the superfluid transition in the presence of a heat current and gravity

The effects of a heat current and gravity in liquid 4He near the superfluid transition are investigated for temperatures above and below T_lambda. We present a renormalization-group calculation based on model F for the Green's function in a self-consistent approximation which in quantum many-particle theory is known as the Hartree approximation. The approach can handle a zero average order parameter above and below T_lambda and includes effects of vortices. We calculate the thermal conductivity and the specific heat for all temperatures T and heat currents Q in the critical regime. Furthermore, we calculate the temperature profile. Below T_lambda we find a second correlation length which describes the dephasing of the order parameter field due to vortices. We find dissipation and mutual friction of the superfluid-normal fluid counterflow and calculate the Gorter-Mellink coefficient A. We compare our theoretical results with recent experiments.Comment: 26 pages, 9 figure

Composite Quarks and Leptons from Dynamical Supersymmetry Breaking without Messengers

We present new theories of dynamical SUSY breaking in which the strong interactions that break SUSY also give rise to composite quarks and leptons with naturally small Yukawa couplings. In these models, SUSY breaking is communicated directly to the composite fields without ``messenger'' interactions. The compositeness scale can be anywhere between 10 TeV and the Planck scale. These models can naturally solve the supersymmetric flavor problem, and generically predict sfermion mass unification independent from gauge unification.Comment: 27 pages, LaTeX; Clarified flavor symmetry of strong interactions; corrected overestimate of FCNC's; conclusions strengthene