Drosophila as a model system to study nonautonomous mechanisms affecting tumour growth and cell death

The study of cancer has represented a central focus in medical research for over a century. The great complexity and constant evolution of the pathology require the use of multiple research model systems and interdisciplinary approaches. This is necessary in order to achieve a comprehensive understanding into the mechanisms driving disease initiation and progression, to aid the development of appropriate therapies. In recent decades, the fruit fly Drosophila melanogaster and its associated powerful genetic tools have become a very attractive model system to study tumour-intrinsic and non-tumour-derived processes that mediate tumour development in vivo. In this review, we will summarize recent work on Drosophila as a model system to study cancer biology. We will focus on the interactions between tumours and their microenvironment, including extrinsic mechanisms affecting tumour growth and how tumours impact systemic host physiology

Collisions of particles in locally AdS spacetimes II Moduli of globally hyperbolic spaces

We investigate 3-dimensional globally hyperbolic AdS manifolds containing "particles", i.e., cone singularities of angles less than $2\pi$ along a time-like graph $\Gamma$. To each such space we associate a graph and a finite family of pairs of hyperbolic surfaces with cone singularities. We show that this data is sufficient to recover the space locally (i.e., in the neighborhood of a fixed metric). This is a partial extension of a result of Mess for non-singular globally hyperbolic AdS manifolds.Comment: 29 pages, 3 figures. v2: 41 pages, improved exposition. To appear, Comm. Math. Phys. arXiv admin note: text overlap with arXiv:0905.182

Hyperbolic manifolds with convex boundary

Let $(M, \partial M)$ be a compact 3-manifold with boundary, which admits a convex co-compact hyperbolic metric. We consider the hyperbolic metrics on $M$ such that the boundary is smooth and strictly convex. We show that the induced metrics on the boundary are exactly the metrics with curvature $K>-1$, and that the third fundamental forms of \dr M are exactly the metrics with curvature $K2\pi$. Each is obtained exactly once. Other related results describe existence and uniqueness properties for other boundary conditions, when the metric which is achieved on \dr M is a linear combination of the first, second and third fundamental forms.Comment: Check the updated version(s) on http://picard.ups-tlse.fr/~schlenker/ Version 2: an error corrected. Version 3: simpler main statement, small corrections, more details on one technical statement. Version 5: one error correcte

Minimal surfaces and particles in 3-manifolds

We use minimal (or CMC) surfaces to describe 3-dimensional hyperbolic, anti-de Sitter, de Sitter or Minkowski manifolds. We consider whether these manifolds admit ``nice'' foliations and explicit metrics, and whether the space of these metrics has a simple description in terms of Teichm\"uller theory. In the hyperbolic settings both questions have positive answers for a certain subset of the quasi-Fuchsian manifolds: those containing a closed surface with principal curvatures at most 1. We show that this subset is parameterized by an open domain of the cotangent bundle of Teichm\"uller space. These results are extended to ``quasi-Fuchsian'' manifolds with conical singularities along infinite lines, known in the physics literature as ``massive, spin-less particles''. Things work better for globally hyperbolic anti-de Sitter manifolds: the parameterization by the cotangent of Teichm\"uller space works for all manifolds. There is another description of this moduli space as the product two copies of Teichm\"uller space due to Mess. Using the maximal surface description, we propose a new parameterization by two copies of Teichm\"uller space, alternative to that of Mess, and extend all the results to manifolds with conical singularities along time-like lines. Similar results are obtained for de Sitter or Minkowski manifolds. Finally, for all four settings, we show that the symplectic form on the moduli space of 3-manifolds that comes from parameterization by the cotangent bundle of Teichm\"uller space is the same as the 3-dimensional gravity one.Comment: 53 pages, no figure. v2: typos corrected and refs adde

Factors associated with alcohol reduction in harmful and hazardous drinkers following alcohol brief intervention in Scotland: a qualitative enquiry

Background: Alcohol Brief Intervention (ABI) uses a motivational counselling approach to support individuals to reduce excessive alcohol consumption. There is growing evidence on ABI’s use within various health care settings, although how they work and which components enhance success is largely unknown. This paper reports on the qualitative part of a mixed methods study. It explores enablers and barriers associated with alcohol reduction following an ABI. It focuses on alcohol’s place within participants’ lives and their personal perspectives on reducing consumption. There are a number of randomised controlled trials in this field though few ABI studies have addressed the experiences of hazardous/harmful drinkers. This study examines factors associated with alcohol reduction in harmful/hazardous drinkers following ABI. Methods: This qualitative study was underpinned by a realist evaluation approach and involved semistructured interviews with ten harmful or hazardous alcohol drinkers. Participants (n = 10) were from the intervention arm of a randomised controlled trial (n = 124). All had received ABI, a 20 min motivational counselling interview, six months previously, and had reduced their alcohol consumption. Interviews were recorded, transcribed verbatim and thematically analysed. Results: Participants described their views on alcohol, its’ place in their lives, their personal perspectives on reducing their consumption and future aspirations. Conclusions: The findings provide an insight into participants’ views on alcohol, ABI, and the barriers and enablers to change. Participants described a cost benefit analysis, with some conscious consideration of the advantages and disadvantages of reducing intake or abstaining from alcohol. Findings suggest that, whilst hospital admission can act as a catalyst, encouraging individuals to reflect on their alcohol consumption through ABI may consolidate this, turning this reflective moment into action. Sustainability may be enhanced by the presence of a ‘significant other’ who encourages and experiences benefit. In addition having a purpose or structure with activities linked to employment and/or social and leisure pursuits offers the potential to enhance and sustain reduced alcohol consumption. Trial registration: Trial registration number TRN NCT00982306 September 22nd 200

A national survey of the availability of intensity-modulated radiation therapy and stereotactic radiosurgery in Canada

<p>Abstract</p> <p>Background</p> <p>The timely and appropriate adoption of new radiation therapy (RT) technologies is a challenge both in terms of providing of optimal patient care and managing health care resources. Relatively little is known regarding the rate at which new RT technologies are adopted in different jurisdictions, and the barriers to implementation of these technologies.</p> <p>Methods</p> <p>Surveys were sent to all radiation oncology department heads in Canada regarding the availability of RT equipment from 2006 to 2010. Data were collected concerning the availability and use of Intensity Modulated Radiation Therapy (IMRT) and stereotactic radiosurgery (SRS), and the obstacles to implementation of these technologies.</p> <p>Results</p> <p>IMRT was available in 37% of responding centers in 2006, increasing to 87% in 2010. In 2010, 72% of centers reported that IMRT was available for all patients who might benefit, and 37% indicated that they used IMRT for "virtually all" head and neck patients. SRS availability increased from 26% in 2006 to 42.5% in 2010. Eighty-two percent of centers reported that patients had access to SRS either directly or by referral. The main barriers for IMRT implementation included the need to train or hire treatment planning staff, whereas barriers to SRS implementation mostly included the need to purchase and/or upgrade existing planning software and equipment.</p> <p>Conclusions</p> <p>The survey showed a growing adoption of IMRT and SRS in Canada, although the latter was available in less than half of responding centers. Barriers to implementation differed for IMRT compared to SRS. Enhancing human resources is an important consideration in the implementation of new RT technologies, due to the multidisciplinary nature of the planning and treatment process.</p

An Outbreak of Serotype 1 Streptococcus pneumoniae Meningitis in Northern Ghana with Features That Are Characteristic of Neisseria meningitidis Meningitis Epidemics

BackgroundThe Kassena-Nankana District (KND) of northern Ghana lies in the African meningitis belt, where epidemics of bacterial meningitis have been reoccurring every 8-12 years. These epidemics are generally caused by Neisseria meningitidis an organism that is considered to be uniquely capable of causing meningitis epidemics MethodsWe recruited all patients with suspected meningitis in the KND between 1998 and 2003. Cerebrospinal fluid samples were collected and analyzed by standard microbiological techniques. Bacterial isolates were subjected to serotyping, multilocus sequence typing (MLST), and antibiotic-resistance testing ResultsA continual increase in the incidence of pneumococcal meningitis was observed from 2000 to 2003. This outbreak exhibited strong seasonality, a broad host age range, and clonal dominance, all of which are characteristic of meningococcal meningitis epidemics in the African meningitis belt. The case-fatality rate for pneumococcal meningitis was 44.4%; the majority of pneumococcal isolates were antibiotic sensitive and expressed the serotype 1 capsule. MLST revealed that these isolates belonged to a clonal complex dominated by sequence type (ST) 217 and its 2 single-locus variants, ST303 and ST612 ConclusionsThe S. pneumoniae ST217 clonal complex represents a hypervirulent lineage with a high propensity to cause meningitis, and our results suggest that this lineage might have the potential to cause an epidemic. Serotype 1 is not included in the currently licensed pediatric heptavalent pneumococcal vaccine. Mass vaccination with a less complex conjugate vaccine that targets hypervirulent serotypes should, therefore, be considere

Retinal Expression of Wnt-Pathway Mediated Genes in Low-Density Lipoprotein Receptor-Related Protein 5 (Lrp5) Knockout Mice

Mutations in low-density lipoprotein receptor-related protein 5 (Lrp5) impair retinal angiogenesis in patients with familial exudative vitreoretinopathy (FEVR), a rare type of blinding vascular eye disease. The defective retinal vasculature phenotype in human FEVR patients is recapitulated in Lrp5 knockout $(Lrp5^{-/-})$ mouse with delayed and incomplete development of retinal vessels. In this study we examined gene expression changes in the developing $Lrp5^{−/−}$ mouse retina to gain insight into the molecular mechanisms that underlie the pathology of FEVR in humans. Gene expression levels were assessed with an Illumina microarray on total RNA from $Lrp5^{−/−}$ and WT retinas isolated on postnatal day (P) 8. Regulated genes were confirmed using RT-qPCR analysis. Consistent with a role in vascular development, we identified expression changes in genes involved in cell-cell adhesion, blood vessel morphogenesis and membrane transport in $Lrp5^{−/−}$ retina compared to WT retina. In particular, tight junction protein claudin5 and amino acid transporter slc38a5 are both highly down-regulated in $Lrp5^{−/−}$ retina. Similarly, several Wnt ligands including Wnt7b show decreased expression levels. Plasmalemma vesicle associated protein (plvap), an endothelial permeability marker, in contrast, is up-regulated consistent with increased permeability in $Lrp5^{−/−}$ retinas. Together these data suggest that Lrp5 regulates multiple groups of genes that influence retinal angiogenesis and may contribute to the pathogenesis of FEVR

Collisions of particles in locally AdS spacetimes I. Local description and global examples

We investigate 3-dimensional globally hyperbolic AdS manifolds containing "particles", i.e., cone singularities along a graph $\Gamma$. We impose physically relevant conditions on the cone singularities, e.g. positivity of mass (angle less than $2\pi$ on time-like singular segments). We construct examples of such manifolds, describe the cone singularities that can arise and the way they can interact (the local geometry near the vertices of $\Gamma$). We then adapt to this setting some notions like global hyperbolicity which are natural for Lorentz manifolds, and construct some examples of globally hyperbolic AdS manifolds with interacting particles.Comment: This is a rewritten version of the first part of arxiv:0905.1823. That preprint was too long and contained two types of results, so we sliced it in two. This is the first part. Some sections have been completely rewritten so as to be more readable, at the cost of slightly less general statements. Others parts have been notably improved to increase readabilit

Household crowding, social mixing patterns and respiratory symptoms in seven countries of the African meningitis belt.

OBJECTIVES: To describe the variation in household crowding and social mixing patterns in the African meningitis belt and to assess any association with self-reported recent respiratory symptoms. METHODS: In 2010, the African Meningococcal Carriage Consortium (MenAfriCar) conducted cross-sectional surveys in urban and rural areas of seven countries. The number of household members, rooms per household, attendance at social gatherings and meeting places were recorded. Associations with self-reported recent respiratory symptoms were analysed by univariate and multivariate regression models. RESULTS: The geometric mean people per room ranged from 1.9 to 2.8 between Ghana and Ethiopia respectively. Attendance at different types of social gatherings was variable by country, ranging from 0.5 to 1.5 per week. Those who attended 3 or more different types of social gatherings a week (frequent mixers) were more likely to be older, male (OR 1.27, p<0.001) and live in urban areas (OR 1.45, p<0.001). Frequent mixing and young age, but not increased household crowding, were associated with higher odds of self-reported respiratory symptoms (aOR 2.2, p<0.001 and OR 2.8, p<0.001 respectively). A limitation is that we did not measure school and workplace attendance. CONCLUSION: There are substantial variations in household crowding and social mixing patterns across the African meningitis belt. This study finds a clear association between age, increased social mixing and respiratory symptoms. It lays the foundation for designing and implementing more detailed studies of social contact patterns in this region