Spherical parameterization for genus zero surfaces using Laplace-Beltrami eigenfunctions

International audienceIn this work, we propose a fast and simple approach to obtain a spherical parameterization of a certain class of closed surfaces without holes. Our approach relies on empirical findings that can be mathematically investigated, to a certain extent, by using Laplace-Beltrami Operator and associated geometrical tools. The mapping proposed here is defined by considering only the three first non-trivial eigenfunctions of the Laplace-Beltrami Operator. Our approach requires a topological condition on those eigenfunctions, whose nodal domains must be 2. We show the efficiency of the approach through numerical experiments performed on cortical surface meshes

It is time to consider third-line options in antiretroviral-experienced paediatric patients?

<p>Abstract</p> <p>Background</p> <p>The historic use of full-dose ritonavir as part of an unboosted protease inhibitor (PI)-based antiretroviral therapy regimen in some South African children contributes to the frequent accumulation of major PI resistance mutations.</p> <p>Methods</p> <p>In order to describe the prevalence of major PI resistance in children failing antiretroviral therapy and to investigate the clinical, immunological and virological outcomes in children with PI resistance, we conducted a cross-sectional study, with a nested case series, following up those children with major PI resistance. The setting was public health sector antiretroviral clinics in the Western Cape province of South Africa, and the subjects were children failing antiretroviral therapy. The following outcome measures were investigated: CD4 count, viral load and resistance mutations.</p> <p>Results</p> <p>Fourteen (17%) of 82 patients, referred from tertiary hospitals, had major PI resistance. All these patients were exposed to regimens that included ritonavir as a single PI. Immune reconstitution and clinical benefit were achieved when using a lopinavir/ritonavir-based treatment regimen in these children with prior PI resistance. At first HIV-1 viral load follow up after initial resistance testing (n = 11), only one patient had a viral load of less than 400 copies/ml; at a subsequent follow up (n = 9), the viral loads of five patients were less than 400 copies/ml. Patients retained on LPV/r had lower viral loads than those switched to a non-nucleoside reverse transcriptase inhibitor (NNRTI). However, two of three patients with follow-up resistance tests accumulated additional PI resistance.</p> <p>Conclusions</p> <p>In children with pre-existing PI resistance, although initially effective, the long-term durability of a lopinavir/ritonavir-based treatment regimen can be compromised by the accumulation of resistance mutations. Furthermore, a second-line NNRTI regimen is often not durable in these patients. As genotypic resistance testing and third-line treatment regimens are costly and limited in availability, we propose eligibility criteria to identify patients with high risk for resistance and guidance on drug selection for children who would benefit from third-line therapy.</p

HIV Prevalence and Impact on Renutrition in Children Hospitalised for Severe Malnutrition in Niger: An Argument for More Systematic Screening

Background: In developing countries, malnutrition is a contributing factor in over 50 % of child deaths. Mortality rates are higher in underweight children, and HIV-infection is known to increase underweight. Our goals were to evaluate the prevalence of HIV among children hospitalised for severe malnutrition (SM) at the Niamey national hospital (Niger), and to compare renutrition and mortality by HIV-status. Methods: Retrospective study based on all children,5 years hospitalised for SM between January 1 st 2008 and July 1 st 2009. HIV-prevalence was the ratio of HIV+ children on the number of children tested. Duration of renutrition and mortality were described using survival curves. Results: During the study period, 477 children were hospitalised for SM. HIV testing was accepted in 470 (98.5%), of which 40 were HIV+ (HIV prevalence (95 % confidence interval) of 8.6 % (6.2–11.5)). Duration of renutrition was longer in HIV+ than HIV2 children (mean: 22 vs. 15 days; p = 0.003). During renutrition, 8 (20%) and 61 (14%) HIV+ and HIV2 children died, respectively (p = 0.81). Conclusion: Around 9 % of children hospitalised for severe malnutrition were HIV infected, while in Niger HIV prevalence i

Mutations in DONSON disrupt replication fork stability and cause microcephalic dwarfism

To ensure efficient genome duplication, cells have evolved numerous factors that promote unperturbed DNA replication and protect, repair and restart damaged forks. Here we identify downstream neighbor of SON (DONSON) as a novel fork protection factor and report biallelic DONSON mutations in 29 individuals with microcephalic dwarfism. We demonstrate that DONSON is a replisome component that stabilizes forks during genome replication. Loss of DONSON leads to severe replication-associated DNA damage arising from nucleolytic cleavage of stalled replication forks. Furthermore, ATM- and Rad3-related (ATR)-dependent signaling in response to replication stress is impaired in DONSON-deficient cells, resulting in decreased checkpoint activity and the potentiation of chromosomal instability. Hypomorphic mutations in DONSON substantially reduce DONSON protein levels and impair fork stability in cells from patients, consistent with defective DNA replication underlying the disease phenotype. In summary, we have identified mutations in DONSON as a common cause of microcephalic dwarfism and established DONSON as a critical replication fork protein required for mammalian DNA replication and genome stability

Surface smoothing: a way back in early brain morphogenesis.

International audienceIn this article we propose to investigate the analogy between early cortical folding process and cortical smoothing by mean curvature flow. First, we introduce a one-parameter model that is able to fit a developmental trajectory as represented in a Volume-Area plot and we propose an efficient optimization strategy for parameter estimation. Second, we validate the model on forty cortical surfaces of preterm newborns by comparing global geometrical indices and trajectories of central sulcus along developmental and simulation time