A Boolean-based machine learning framework identifies predictive biomarkers of HSP90-targeted therapy response in prostate cancer

Precision medicine has emerged as an important paradigm in oncology, driven by the significant heterogeneity of individual patients' tumour. A key prerequisite for effective implementation of precision oncology is the development of companion biomarkers that can predict response to anti-cancer therapies and guide patient selection for clinical trials and/or treatment. However, reliable predictive biomarkers are currently lacking for many anti-cancer therapies, hampering their clinical application. Here, we developed a novel machine learning-based framework to derive predictive multi-gene biomarker panels and associated expression signatures that accurately predict cancer drug sensitivity. We demonstrated the power of the approach by applying it to identify response biomarker panels for an Hsp90-based therapy in prostate cancer, using proteomic data profiled from prostate cancer patient-derived explants. Our approach employs a rational feature section strategy to maximise model performance, and innovatively utilizes Boolean algebra methods to derive specific expression signatures of the marker proteins. Given suitable data for model training, the approach is also applicable to other cancer drug agents in different tumour settings.Sung-Young Shin, Margaret M. Centenera, Joshua T. Hodgson, Elizabeth V. Nguyen, Lisa M. Butler, Roger J. Daly and Lan K. Nguye

Generation of Large-Scale Vorticity in a Homogeneous Turbulence with a Mean Velocity Shear

An effect of a mean velocity shear on a turbulence and on the effective force which is determined by the gradient of Reynolds stresses is studied. Generation of a mean vorticity in a homogeneous incompressible turbulent flow with an imposed mean velocity shear due to an excitation of a large-scale instability is found. The instability is caused by a combined effect of the large-scale shear motions (''skew-induced" deflection of equilibrium mean vorticity) and ''Reynolds stress-induced" generation of perturbations of mean vorticity. Spatial characteristics, such as the minimum size of the growing perturbations and the size of perturbations with the maximum growth rate, are determined. This instability and the dynamics of the mean vorticity are associated with the Prandtl's turbulent secondary flows. This instability is similar to the mean-field magnetic dynamo instability. Astrophysical applications of the obtained results are discussed.Comment: 8 pages, 3 figures, REVTEX4, submitted to Phys. Rev.

‘Growing your own’: a multi-level modelling approach to understanding personal food growing trends and motivations in Europe

Growing food for personal and family consumption is a significant global activity, but one that has received insufficient academic attention, particularly in developed countries. This paper uses data from the European Quality of Life Survey (EQLS) to address three areas of particular concern: the prevalence of growing your own food and how this has changed over time; the individual and household context in which growing takes place; and whether those who grow their own food are happier than those who do not. Results showed that there was a marked increase in growing your own food in Europe, in the period 2003–2007. This increase is largely associated with poorer households and thus, possibly, economic hardship. In the UK however the increase in growing your own food is predominantly associated with older middle class households. Across Europe, whether causal or not, those who grew their own were happier than those who did not. The paper therefore concludes that claims about the gentrification of growing your own may be premature. Despite contrary evidence from the UK, the dominant motive across Europe appears to be primarily economic — to reduce household expenditure whilst ensuring a supply of fresh food

Models of peer support to remediate post-intensive care syndrome: A report developed by the SCCM Thrive International Peer Support Collaborative

Objective: Patients and caregivers can experience a range of physical, psychological, and cognitive problems following critical care discharge. The use of peer support has been proposed as an innovative support mechanism. Design: We sought to identify technical, safety and procedural aspects of existing operational models of peer support, among the Society of Critical Care Medicine Thrive Peer Support Collaborative. We also sought to categorize key distinctions between these models and elucidate barriers and facilitators to implementation. Subjects: 17 Thrive sites from the USA, UK, and Australia were represented by a range of healthcare professionals. Interventions: Via an iterative process of in-person and email/conference calls, members of the Collaborative, defined the key areas on which peer support models could be defined and compared; collected detailed self-reports from all sites; reviewed the information and identified clusters of models. Barriers and challenges to implementation of peer support models were also documented. Results: Within the Thrive Collaborative, six general models of peer support were identified: Community based, Psychologist-led outpatient, Models based within ICU follow-up clinics, Online, Groups based within ICU and Peer mentor models. The most common barriers to implementation were: recruitment to groups, personnel input and training: sustainability and funding, risk management and measuring success. Conclusion: A number of different models of peer support are currently being developed to help patients and families recover and grow in the post-critical care setting

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02

Observation of a new chi_b state in radiative transitions to Upsilon(1S) and Upsilon(2S) at ATLAS

The chi_b(nP) quarkonium states are produced in proton-proton collisions at the Large Hadron Collider (LHC) at sqrt(s) = 7 TeV and recorded by the ATLAS detector. Using a data sample corresponding to an integrated luminosity of 4.4 fb^-1, these states are reconstructed through their radiative decays to Upsilon(1S,2S) with Upsilon->mu+mu-. In addition to the mass peaks corresponding to the decay modes chi_b(1P,2P)->Upsilon(1S)gamma, a new structure centered at a mass of 10.530+/-0.005 (stat.)+/-0.009 (syst.) GeV is also observed, in both the Upsilon(1S)gamma and Upsilon(2S)gamma decay modes. This is interpreted as the chi_b(3P) system.Comment: 5 pages plus author list (18 pages total), 2 figures, 1 table, corrected author list, matches final version in Physical Review Letter

Search for displaced vertices arising from decays of new heavy particles in 7 TeV pp collisions at ATLAS

We present the results of a search for new, heavy particles that decay at a significant distance from their production point into a final state containing charged hadrons in association with a high-momentum muon. The search is conducted in a pp-collision data sample with a center-of-mass energy of 7 TeV and an integrated luminosity of 33 pb^-1 collected in 2010 by the ATLAS detector operating at the Large Hadron Collider. Production of such particles is expected in various scenarios of physics beyond the standard model. We observe no signal and place limits on the production cross-section of supersymmetric particles in an R-parity-violating scenario as a function of the neutralino lifetime. Limits are presented for different squark and neutralino masses, enabling extension of the limits to a variety of other models.Comment: 8 pages plus author list (20 pages total), 8 figures, 1 table, final version to appear in Physics Letters

Reducing heterotic M-theory to five dimensional supergravity on a manifold with boundary

This paper constructs the reduction of heterotic $M$-theory in eleven dimensions to a supergravity model on a manifold with boundary in five dimensions using a Calabi-Yau three-fold. New results are presented for the boundary terms in the action and for the boundary conditions on the bulk fields. Some general features of dualisation on a manifold with boundary are used to explain the origin of some topological terms in the action. The effect of gaugino condensation on the fermion boundary conditions leads to a `twist' in the chirality of the gravitino which can provide an uplifting mechanism in the vacuum energy to cancel the cosmological constant after moduli stabilisation.Comment: 16 pages, RevTe

Measurement of the inclusive isolated prompt photon cross-section in pp collisions at sqrt(s)= 7 TeV using 35 pb-1 of ATLAS data

A measurement of the differential cross-section for the inclusive production of isolated prompt photons in pp collisions at a center-of-mass energy sqrt(s) = 7 TeV is presented. The measurement covers the pseudorapidity ranges |eta|<1.37 and 1.52<=|eta|<2.37 in the transverse energy range 45<=E_T<400GeV. The results are based on an integrated luminosity of 35 pb-1, collected with the ATLAS detector at the LHC. The yields of the signal photons are measured using a data-driven technique, based on the observed distribution of the hadronic energy in a narrow cone around the photon candidate and the photon selection criteria. The results are compared with next-to-leading order perturbative QCD calculations and found to be in good agreement over four orders of magnitude in cross-section.Comment: 7 pages plus author list (18 pages total), 2 figures, 4 tables, final version published in Physics Letters