Sorafenib dose escalation is not uniformly associated with blood pressure elevations in normotensive patients with advanced malignancies.

Hypertension after treatment with vascular endothelial growth factor (VEGF) receptor inhibitors is associated with superior treatment outcomes for advanced cancer patients. To determine whether increased sorafenib doses cause incremental increases in blood pressure (BP), we measured 12-h ambulatory BP in 41 normotensive advanced solid tumor patients in a randomized dose-escalation study. After 7 days' treatment (400 mg b.i.d.), mean diastolic BP (DBP) increased in both study groups. After dose escalation, group A (400 mg t.i.d.) had marginally significant further increase in 12-h mean DBP (P = 0.053), but group B (600 mg b.i.d.) did not achieve statistically significant increases (P = 0.25). Within groups, individuals varied in BP response to sorafenib dose escalation, but these differences did not correlate with changes in steady-state plasma sorafenib concentrations. These findings in normotensive patients suggest BP is a complex pharmacodynamic biomarker of VEGF inhibition. Patients have intrinsic differences in sensitivity to sorafenib's BP-elevating effects

Eliminating Malaria Vectors.

Malaria vectors which predominantly feed indoors upon humans have been locally eliminated from several settings with insecticide treated nets (ITNs), indoor residual spraying or larval source management. Recent dramatic declines of An. gambiae in east Africa with imperfect ITN coverage suggest mosquito populations can rapidly collapse when forced below realistically achievable, non-zero thresholds of density and supporting resource availability. Here we explain why insecticide-based mosquito elimination strategies are feasible, desirable and can be extended to a wider variety of species by expanding the vector control arsenal to cover a broader spectrum of the resources they need to survive. The greatest advantage of eliminating mosquitoes, rather than merely controlling them, is that this precludes local selection for behavioural or physiological resistance traits. The greatest challenges are therefore to achieve high biological coverage of targeted resources rapidly enough to prevent local emergence of resistance and to then continually exclude, monitor for and respond to re-invasion from external populations

Direct CP violation in charm and flavor mixing beyond the SM

We analyze possible interpretations of the recent LHCb evidence for CP violation in D meson decays in terms of physics beyond the Standard Model. On general grounds, models in which the primary source of flavor violation is linked to the breaking of chiral symmetry (left-right flavor mixing) are natural candidates to explain this effect, via enhanced chromomagnetic operators. In the case of supersymmetric models, we identify two motivated scenarios: disoriented A-terms and split families. These structures predict other non-standard signals, such as nuclear EDMs close to their present bounds and, possibly, tiny but visible deviations in K and B physics, or even sizable flavor-violating processes involving the top quark or the stops. Some of these connections, especially the one with nuclear EDMs, hold beyond supersymmetry, as illustrated with the help of prototype non-supersymmetric models.Comment: 30 pages, 6 figure

NLSP Gluino Search at the Tevatron and early LHC

We investigate the collider phenomenology of gluino-bino co-annihilation scenario both at the Tevatron and 7 TeV LHC. This scenario can be realized, for example, in a class of realistic supersymmetric models with non-universal gaugino masses and t-b-\tau Yukawa unification. The NLSP gluino and LSP bino should be nearly degenerate in mass, so that the typical gluino search channels involving leptons or hard jets are not available. Consequently, the gluino can be lighter than various bounds on its mass from direct searches. We propose a new search for NLSP gluino involving multi-b final states, arising from the three-body decay \tilde{g}-> b\bar{b}\tilde{\chi}_1^0. We identify two realistic models with gluino mass of around 300 GeV for which the three-body decay is dominant, and show that a 4.5 \sigma observation sensitivity can be achieved at the Tevatron with an integrated luminosity of 10 fb^{-1}. For the 7 TeV LHC with 50 pb^{-1} of integrated luminosity, the number of signal events for the two models is O(10), to be compared with negligible SM background event.Comment: 14 pages, 4 figures and 3 tables, minor modifications made and accepted for publication in JHE

General Messenger Gauge Mediation

We discuss theories of gauge mediation in which the hidden sector consists of two subsectors which are weakly coupled to each other. One sector is made up of messengers and the other breaks supersymmetry. Each sector by itself may be strongly coupled. We provide a unifying framework for such theories and discuss their predictions in different settings. We show how this framework incorporates all known models of messengers. In the case of weakly-coupled messengers interacting with spurions through the superpotential, we prove that the sfermion mass-squared is positive, and furthermore, that there is a lower bound on the ratio of the sfermion mass to the gaugino mass.Comment: 37 pages; minor change

Partially Supersymmetric Composite Higgs Models

We study the idea of the Higgs as a pseudo-Goldstone boson within the framework of partial supersymmetry in Randall-Sundrum scenarios and their CFT duals. The Higgs and third generation of the MSSM are composites arising from a strongly coupled supersymmetric CFT with global symmetry SO(5) spontaneously broken to SO(4), whilst the light generations and gauge fields are elementary degrees of freedom whose couplings to the strong sector explicitly break the global symmetry as well as supersymmetry. The presence of supersymmetry in the strong sector may allow the compositeness scale to be raised to ~10 TeV without fine tuning, consistent with the bounds from precision electro-weak measurements and flavour physics. The supersymmetric flavour problem is also solved. At low energies, this scenario reduces to the "More Minimal Supersymmetric Standard Model" where only stops, Higgsinos and gauginos are light and within reach of the LHC.Comment: 28 pages. v2 minor changes and Refs. adde

CP Violation in Supersymmetry with Effective Minimal Flavour Violation

We analyze CP violation in supersymmetry with Effective Minimal Flavour Violation, as recently proposed in arXiv:1011.0730. Unlike the case of standard Minimal Flavour Violation, we show that all the phases allowed by the flavour symmetry can be sizable without violating existing Electric Dipole Moment constraints, thus solving the SUSY CP problem. The EDMs at one and two loops are precisely analyzed as well as their correlations with the expected CP asymmetries in B physics.Comment: 22 pages, 7 figures. v2: Discussion in section 2 extended, conclusions unchanged. Matches published versio

Skyrmion Multi-Walls

Skyrmion walls are topologically-nontrivial solutions of the Skyrme system which are periodic in two spatial directions. We report numerical investigations which show that solutions representing parallel multi-walls exist. The most stable configuration is that of the square $N$-wall, which in the $N\to\infty$ limit becomes the cubically-symmetric Skyrme crystal. There is also a solution resembling parallel hexagonal walls, but this is less stable.Comment: 7 pages, 1 figur

An affordable, quality-assured community-based system for high-resolution entomological surveillance of vector mosquitoes that reflects human malaria infection risk patterns.

ABSTRACT: BACKGROUND: More sensitive and scalable entomological surveillance tools are required to monitor low levels of transmission that are increasingly common across the tropics, particularly where vector control has been successful. A large-scale larviciding programme in urban Dar es Salaam, Tanzania is supported by a community-based (CB) system for trapping adult mosquito densities to monitor programme performance. Methodology An intensive and extensive CB system for routine, longitudinal, programmatic surveillance of malaria vectors and other mosquitoes using the Ifakara Tent Trap (ITT-C) was developed in Urban Dar es Salaam, Tanzania, and validated by comparison with quality assurance (QA) surveys using either ITT-C or human landing catches (HLC), as well as a cross-sectional survey of malaria parasite prevalence in the same housing compounds. RESULTS: Community-based ITT-C had much lower sensitivity per person-night of sampling than HLC (Relative Rate (RR) [95% Confidence Interval (CI)] = 0.079 [0.051, 0.121], P < 0.001 for Anopheles gambiae s.l. and 0.153 [0.137, 0.171], P < 0.001 for Culicines) but only moderately differed from QA surveys with the same trap (0.536 [0.406,0.617], P = 0.001 and 0.747 [0.677,0.824], P < 0.001, for An. gambiae or Culex respectively). Despite the poor sensitivity of the ITT per night of sampling, when CB-ITT was compared with QA-HLC, it proved at least comparably sensitive in absolute terms (171 versus 169 primary vectors caught) and cost-effective (153US$versus 187US$ per An. gambiae caught) because it allowed more spatially extensive and temporally intensive sampling (4284 versus 335 trap nights distributed over 615 versus 240 locations with a mean number of samples per year of 143 versus 141). Despite the very low vectors densities (Annual estimate of about 170 An gambiae s.l bites per person per year), CB-ITT was the only entomological predictor of parasite infection risk (Odds Ratio [95% CI] = 4.43[3.027,7. 454] per An. gambiae or Anopheles funestus caught per night, P =0.0373). Discussion and conclusion CB trapping approaches could be improved with more sensitive traps, but already offer a practical, safe and affordable system for routine programmatic mosquito surveillance and clusters could be distributed across entire countries by adapting the sample submission and quality assurance procedures accordingly

Top mass dependent alpha_s^3 corrections to B-meson mixing in the MSSM

We compute the top mass dependent NLO strong interaction matching conditions to the Delta F=2 effective Hamiltonian in the general MSSM. We study the relevance of such corrections, comparing its size with that of previously known NLO corrections in the limit mt->0, in scenarios with degeneracy, alignment, and hierarchical squarks. We find that, while these corrections are generally small, there are regions in the parameter space where the contributions to the Wilson coefficients C1 and C4 could partially overcome the expected suppression m_t/M_SUSY.Comment: 15 pages, 6 figure