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

The impact of contact tracing in clustered populations

The tracing of potentially infectious contacts has become an important part of the control strategy for many infectious diseases, from early cases of novel infections to endemic sexually transmitted infections. Here, we make use of mathematical models to consider the case of partner notification for sexually transmitted infection, however these models are sufficiently simple to allow more general conclusions to be drawn. We show that, when contact network structure is considered in addition to contact tracing, standard “mass action” models are generally inadequate. To consider the impact of mutual contacts (specifically clustering) we develop an improvement to existing pairwise network models, which we use to demonstrate that ceteris paribus, clustering improves the efficacy of contact tracing for a large region of parameter space. This result is sometimes reversed, however, for the case of highly effective contact tracing. We also develop stochastic simulations for comparison, using simple re-wiring methods that allow the generation of appropriate comparator networks. In this way we contribute to the general theory of network-based interventions against infectious disease

Heterotic strings on G_2 orbifolds

We study compactification of heterotic strings to three dimensions on orbifolds of G_2 holonomy. We consider the standard embedding and show that the gauge group is broken from E_8 x E_8 or SO(32) to F_4 x E_8 or SO(25) respectively. We also compute the spectrum of massless states and compare with the results obtained from reduction of the 10-dimensional fields. Non-standard embeddings are discussed briefly. For type II compactifications we verify that IIB and IIA have equal massless spectrum.Comment: LaTex, 21 page

Maternal self-efficacy and 1–5-year-old children's brushing habits

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73681/1/j.1600-0528.2007.00313.x.pd

A special road to AdS vacua

We apply the techniques of special Kaehler geometry to investigate AdS_4 vacua of general N=2 gauged supergravities underlying flux compactifications of type II theories. We formulate the scalar potential and its extremization conditions in terms of a triplet of prepotentials P_x and their special Kaehler covariant derivatives only, in a form that recalls the potential and the attractor equations of N=2 black holes. We propose a system of first order equations for the P_x which generalize the supersymmetry conditions and yield non-supersymmetric vacua. Special geometry allows us to recast these equations in algebraic form, and we find an infinite class of new N=0 and N=1 AdS_4 solutions, displaying a rich pattern of non-trivial charges associated with NSNS and RR fluxes. Finally, by explicit evaluation of the entropy function on the solutions, we derive a U-duality invariant expression for the cosmological constant and the central charges of the dual CFT's.Comment: 41 pages; v2, v3: minor improvements, references added, published versio

Moduli Stabilization and Cosmology of Type IIB on SU(2)-Structure Orientifolds

We consider type IIB flux compactifications on six-dimensional SU(2)-structure manifolds with O5- and O7-planes. These six-dimensional spaces allow not only for F_3 and H_3 fluxes but also for F_1 and F_5 fluxes. We derive the four-dimensional N=1 scalar potential for such compactifications and present one explicit example of a fully stabilized AdS vacuum with large volume and small string coupling. We then discuss cosmological aspects of these compactifications and derive several no-go theorems that forbid dS vacua and slow-roll inflation under certain conditions. We also study concrete examples of cosets and twisted tori and find that our no-go theorems forbid dS vacua and slow-roll inflation in all but one of them. For the latter we find a dS critical point with \epsilon numerically zero. However, the point has two tachyons and eta-parameter \eta \approx -3.1.Comment: 35 pages + appendices, LaTeX2e; v2: numerical dS extremum added, typos corrected, references adde

Revisiting Lynam's notion of the "fledgling psychopath": are HIA-CP children truly psychopathic-like?

<p>Abstract</p> <p>Background</p> <p>In his developmental model of emerging psychopathy, Lynam proposed that the "fledgling psychopath" is most likely to be located within a subgroup of children elevated in both hyperactivity/inattention/impulsivity (HIA) and conduct problems (CP). This approach has garnered some empirical support. However, the extent to which Lynam's model captures children who resemble psychopathy with regard to the core affective and interpersonal features remains unclear.</p> <p>Methods</p> <p>In the present study, we investigated this issue within a large community sample of youth (<it>N </it>= 617). Four groups (non-HIA-CP, HIA-only, CP-only, and HIA-CP), defined on the basis of teacher reports of the Strengths and Difficulties Questionnaire (SDQ), were compared with respect to parent-reported psychopathic-like traits and subjective emotional reactivity in response to unpleasant, emotionally-laden pictures from the International Affective Pictures System (IAPS).</p> <p>Results</p> <p>Results did not support Lynam's model. HIA-CP children did not appear most psychopathic-like on dimensions of callous-unemotional and narcissistic personality, nor did they report reduced emotional reactivity to the IAPS relative to the other children. Post-hoc regression analyses revealed a significant moderation such that elevated HIA weakened the association between CP and emotional underarousal.</p> <p>Conclusions</p> <p>Implications of these findings with regard to the development of psychopathy are discussed.</p

BPS-like potential for compactifications of heterotic M-theory?

We analyze the possibility to rewrite the action of Horava-Witten theory in a BPS-like form, which means that it is given as a sum of squares of the supersymmetry conditions. To this end we compactify the theory on a seven dimensional manifold of SU(3) structure and rewrite the scalar curvature of the compactification manifold in terms of the SU(3) structure forms. This shows that a BPS-like form cannot be obtained in general, but only for certain types of compactifications.Comment: 31 pages, no figures, references added, typos correcte

Water quality is a poor predictor of recreational hotspots in England

Maintaining and improving water quality is key to the protection and restoration of aquatic ecosystems, which provide important benefits to society. In Europe, the Water Framework Directive (WFD) defines water quality based on a set of biological, hydro-morphological and chemical targets, and aims to reach good quality conditions in all river bodies by the year 2027. While recently it has been argued that achieving these goals will deliver and enhance ecosystem services, in particular recreational services, there is little empirical evidence demonstrating so. Here we test the hypothesis that good water quality is associated with increased utilization of recreational services, combining four surveys covering walking, boating, fishing and swimming visits, together with water quality data for all water bodies in eight River Basin Districts (RBDs) in England. We compared the percentage of visits in areas of good water quality to a set of null models accounting for population density, income, age distribution, travel distance, public access, and substitutability. We expect such association to be positive, at least for fishing (which relies on fish stocks) and swimming (with direct contact to water). We also test if these services have stronger association with water quality relative to boating and walking alongside rivers, canals or lakeshores. In only two of eight RBDs (Northumbria and Anglian) were both criteria met (positive association, strongest for fishing and swimming) when comparing to at least one of the null models. This conclusion is robust to variations in dataset size. Our study suggests that achieving the WFD water quality goals may not enhance recreational ecosystem services, and calls for further empirical research on the connection between water quality and ecosystem services