Universal de Sitter solutions at tree-level

Type IIA string theory compactified on SU(3)-structure manifolds with orientifolds allows for classical de Sitter solutions in four dimensions. In this paper we investigate these solutions from a ten-dimensional point of view. In particular, we demonstrate that there exists an attractive class of de Sitter solutions, whose geometry, fluxes and source terms can be entirely written in terms of the universal forms that are defined on all SU(3)-structure manifolds. These are the forms J and Omega, defining the SU(3)-structure itself, and the torsion classes. The existence of such universal de Sitter solutions is governed by easy-to-verify conditions on the SU(3)-structure, rendering the problem of finding dS solutions purely geometrical. We point out that the known (unstable) solution coming from the compactification on SU(2)x SU(2) is of this kind.Comment: 20 pages, 3 figures, v2: added reference

The problematic backreaction of SUSY-breaking branes

In this paper we investigate the localisation of SUSY-breaking branes which, in the smeared approximation, support specific non-BPS vacua. We show, for a wide class of boundary conditions, that there is no flux vacuum when the branes are described by a genuine delta-function. Even more, we find that the smeared solution is the unique solution with a regular brane profile. Our setup consists of a non-BPS AdS_7 solution in massive IIA supergravity with smeared anti-D6-branes and fluxes T-dual to ISD fluxes in IIB supergravity.Comment: 27 pages, Latex2e, 5 figure

Black holes in supergravity and integrability

Stationary black holes of massless supergravity theories are described by certain geodesic curves on the target space that is obtained after dimensional reduction over time. When the target space is a symmetric coset space we make use of the group-theoretical structure to prove that the second order geodesic equations are integrable in the sense of Liouville, by explicitly constructing the correct amount of Hamiltonians in involution. This implies that the Hamilton-Jacobi formalism can be applied, which proves that all such black hole solutions, including non-extremal solutions, possess a description in terms of a (fake) superpotential. Furthermore, we improve the existing integration method by the construction of a Lax integration algorithm that integrates the second order equations in one step instead of the usual two step procedure. We illustrate this technology with a specific example.Comment: 44 pages, small typos correcte

Epidemiology of frequent attenders: a 3-year historic cohort study comparing attendance, morbidity and prescriptions of one-year and persistent frequent attenders

BACKGROUND: General Practitioners spend a disproportionate amount of time on frequent attenders. So far, trials on the effect of interventions on frequent attenders have shown negative results. However, these trials were conducted in short-term frequent attenders. It would be more reasonable to target intervention at persistent frequent attenders. Typical characteristics of persistent frequent attenders, as opposed to 1-year frequent attenders and non-frequent attenders, may generate hypotheses regarding modifiable factors on which new randomized trials may be designed. METHODS: We used the data of all 28,860 adult patients from 5 primary healthcare centers. Frequent attenders were patients whose attendance rate ranked in the (age and sex adjusted) top 10 percent during 1 year (1-year frequent attenders) or 3 years (persistent frequent attenders). All other patients on the register over the 3-year period were referred to as non-frequent attenders. The lists of medical problems coded by the GP using the International Classification of Primary Care (ICPC) were used to assess morbidity.First, we determined which proportion of 1-year frequent attenders was still a frequent attender during the next two consecutive years and calculated the GPs' workload for these patients. Second, we compared morbidity and number of prescriptions for non-frequent attenders, 1-year frequent attenders and persistent frequent attenders. RESULTS: Of all 1-year frequent attenders, 15.4% became a persistent frequent attender equal to 1.6% of all patients. The 1-year frequent attenders (3,045; 10.6%) were responsible for 39% of the face-to-face consultations; the 470 patients who would become persistent frequent attenders (1.6%) were responsible for 8% of all consultations in 2003. Persistent frequent attenders presented more social problems, more psychiatric problems and medically unexplained physical symptoms, but also more chronic somatic diseases (especially diabetes). They received more prescriptions for psychotropic medication. CONCLUSION: One out of every seven 1-year-frequent attenders (15.4%) becomes a persistent frequent attender. Compared with non-frequent attenders, and 1-year frequent attenders, persistent frequent attenders consume more health care and are diagnosed not only with more somatic diseases but especially more social problems, psychiatric problems and medically unexplained physical symptoms

Immediate thoracotomy for penetrating injuries: Ten years' experience at a Dutch level I trauma center

Background: An emergency department thoracotomy (EDT) or an emergency thoracotomy (ET) in the operating theater are both beneficial in selected patients following thoracic penetrating injuries. Since outcome-descriptive European studies are lacking, the aim of this retrospective study was to evaluate ten years of experience at a Dutch level I trauma center. Method: Data on patients who underwent an immediate thoracotomy after sustaining a penetrating thoracic injury between October 2000 and January 2011 were collected from the trauma registry and hospital files. Descriptive and univariate analyses were performed. Results: Among 56 patients, 12 underwent an EDT and 44 an ET. Forty-six patients sustained one or multiple stab wounds, versus ten with one or multiple gunshot wounds. Patients who had undergone an EDT had a lower GCS (p < 0. 001), lower pre-hospital RTS and hospital triage RTS (p < 0. 001 and p = 0. 009, respectively), and a lower SBP (p = 0. 038). A witnessed loss of signs of life generally occurred in EDT patients and was accompanied by 100 % mortality. Survival following EDT was 25 %, which was significantly lower than in the ET group (75 %; p = 0. 002). Survivors had lower ISS (p = 0. 011), lower rates of pre-hospital (p = 0. 031) and hospital (p = 0. 003) hemodynamic instability, and a lower prevalence of concomitant abdominal injury (p = 0. 002). Conclusion: The overall survival rate in our study was 64 %. The outcome of immediate thoracotomy performed in this level I trauma center was similar to those obtained in high-incidence regions like the US and South Africa. This suggests that trauma units where immediate thoracotomies are not part of the daily routine can achieve similar results, if properly trained

A Global View on The Search for de-Sitter Vacua in (type IIA) String Theory

The search for classically stable Type IIA de-Sitter vacua typically starts with an ansatz that gives Anti-de-Sitter supersymmetric vacua and then raises the cosmological constant by modifying the compactification. As one raises the cosmological constant, the couplings typically destabilize the classically stable vacuum, so the probability that this approach will lead to a classically stable de-Sitter vacuum is Gaussianly suppressed. This suggests that classically stable de-Sitter vacua in string theory (at least in the Type IIA region), especially those with relatively high cosmological constants, are very rare. The probability that a typical de-Sitter extremum is classically stable (i.e., tachyon-free) is argued to be Gaussianly suppressed as a function of the number of moduli.Comment: 23 pages, 5 figures; v2, v3: arguments improved, references added; v4: version to appear in JHE

Geometry sensing by dendritic cells dictates spatial organization and PGE2-induced dissolution of podosomes

Assembly and disassembly of adhesion structures such as focal adhesions (FAs) and podosomes regulate cell adhesion and differentiation. On antigen-presenting dendritic cells (DCs), acquisition of a migratory and immunostimulatory phenotype depends on podosome dissolution by prostaglandin E2 (PGE2). Whereas the effects of physico-chemical and topographical cues have been extensively studied on FAs, little is known about how podosomes respond to these signals. Here, we show that, unlike for FAs, podosome formation is not controlled by substrate physico-chemical properties. We demonstrate that cell adhesion is the only prerequisite for podosome formation and that substrate availability dictates podosome density. Interestingly, we show that DCs sense 3-dimensional (3-D) geometry by aligning podosomes along the edges of 3-D micropatterned surfaces. Finally, whereas on a 2-dimensional (2-D) surface PGE2 causes a rapid increase in activated RhoA levels leading to fast podosome dissolution, 3-D geometric cues prevent PGE2-mediated RhoA activation resulting in impaired podosome dissolution even after prolonged stimulation. Our findings indicate that 2-D and 3-D geometric cues control the spatial organization of podosomes. More importantly, our studies demonstrate the importance of substrate dimensionality in regulating podosome dissolution and suggest that substrate dimensionality plays an important role in controlling DC activation, a key process in initiating immune responses

Vaccine antigens modulate the innate response of monocytes to Al(OH)3.

Aluminum-based adjuvants have widely been used in human vaccines since 1926. In the absence of antigens, aluminum-based adjuvants can initiate the inflammatory preparedness of innate cells, yet the impact of antigens on this response has not been investigated so far. In this study, we address the modulating effect of vaccine antigens on the monocyte-derived innate response by comparing processes initiated by Al(OH)3 and by Infanrix, an Al(OH)3-adjuvanted trivalent combination vaccine (DTaP), containing diphtheria toxoid (D), tetanus toxoid (T) and acellular pertussis (aP) vaccine antigens. A systems-wide analysis of stimulated monocytes was performed in which full proteome analysis was combined with targeted transcriptome analysis and cytokine analysis. This comprehensive study revealed four major differences in the monocyte response, between plain Al(OH)3 and DTaP stimulation conditions: (I) DTaP increased the anti-inflammatory cytokine IL-10, whereas Al(OH)3 did not; (II) Al(OH)3 increased the gene expression of IFNγ, IL-2 and IL-17a in contrast to the limited induction or even downregulation by DTaP; (III) increased expression of type I interferons-induced proteins was not observed upon DTaP stimulation, but was observed upon Al(OH)3 stimulation; (IV) opposing regulation of protein localization pathways was observed for Al(OH)3 and DTaP stimulation, related to the induction of exocytosis by Al(OH)3 alone. This study highlights that vaccine antigens can antagonize Al(OH)3-induced programming of the innate immune responses at the monocyte level

Vaccine responses in newborns.

Immunisation of the newborn represents a key global strategy in overcoming morbidity and mortality due to infection in early life. Potential limitations, however, include poor immunogenicity, safety concerns and the development of tolerogenicity or hypo-responsiveness to either the same antigen and/or concomitant antigens administered at birth or in the subsequent months. Furthermore, the neonatal immunological milieu is polarised towards Th2-type immunity with dampening of Th1-type responses and impaired humoral immunity, resulting in qualitatively and quantitatively poorer antibody responses compared to older infants. Innate immunity also shows functional deficiency in antigen-presenting cells: the expression and signalling of Toll-like receptors undergo maturational changes associated with distinct functional responses. Nevertheless, the effectiveness of BCG, hepatitis B and oral polio vaccines, the only immunisations currently in use in the neonatal period, is proof of concept that vaccines can be successfully administered to the newborn via different routes of delivery to induce a range of protective mechanisms for three different diseases. In this review paper, we discuss the rationale for and challenges to neonatal immunisation, summarising progress made in the field, including lessons learnt from newborn vaccines in the pipeline. Furthermore, we explore important maternal, infant and environmental co-factors that may impede the success of current and future neonatal immunisation strategies. A variety of approaches have been proposed to overcome the inherent regulatory constraints of the newborn innate and adaptive immune system, including alternative routes of delivery, novel vaccine configurations, improved innate receptor agonists and optimised antigen-adjuvant combinations. Crucially, a dual strategy may be employed whereby immunisation at birth is used to prime the immune system in order to improve immunogenicity to subsequent homologous or heterologous boosters in later infancy. Similarly, potent non-specific immunomodulatory effects may be elicited when challenged with unrelated antigens, with the potential to reduce the overall risk of infection and allergic disease in early life

Complex Interactions between Soil-Transmitted Helminths and Malaria in Pregnant Women on the Thai-Burmese Border

Intestinal worms, particularly hookworm and whipworm, can cause anaemia, which is harmful for pregnant women. The WHO recommends deworming in pregnancy in areas where hookworm infections are frequent. Some studies indicate that coinfection with worms and malaria adversely affects pregnancy whereas other studies have shown that coinfection with worms might reduce the severity of malaria. On the Thai-Burmese border malaria in pregnancy has been an important cause of maternal death. We examined the relationship between intestinal helminth infections in pregnant women and their malaria risk in our antenatal care units. In total 70% of pregnant women had worm infections, mostly hookworm, but also roundworm and whipworm; hookworm was associated with mild anaemia although ova counts were not high. Women infected with hookworm had more malaria and their babies had a lower birth weight than women without hookworm. In contrast women with roundworm infections had the lowest rates of malaria in pregnancy. Deworming eliminates all worms. In this area it is unclear whether mass deworming would be beneficial