Mutational Heterogeneity in Melanoma: An Inconvenient Truth

Identification of oncogenic BRAF mutations in primary and metastatic melanomas supports a linear model of clonal evolution in cancer. Some mutational studies, however, have failed to identify BRAF mutations in metastatic tumors from patients with BRAFmutant primary melanomas. Using a combination of methods, Riveiro-Falkenbach et al. (2015) assert that technical issues, and not clonal heterogeneity, may explain prior discordant mutational results

Prevention of cisplatin-induced hearing loss in children: Informing the design of future clinical trials.

Cisplatin is an essential chemotherapeutic agent in the treatment of many pediatric cancers. Unfortunately, cisplatin-induced hearing loss (CIHL) is a common, clinically significant side effect with life-long ramifications, particularly for young children. ACCL05C1 and ACCL0431 are two recently completed Childrens Oncology Group studies focused on the measurement and prevention of CIHL. The purpose of this paper was to gain insights from ACCL05C1 and ACCL0431, the first published cooperative group studies dedicated solely to CIHL, to inform the design of future pediatric otoprotection trials. Use of otoprotective agents is an attractive strategy for preventing CIHL, but their successful development must overcome a unique constellation of methodological challenges related to translating preclinical research into clinical trials that are feasible, evaluate practical interventions, and limit risk. Issues particularly important for children include use of appropriate methods for hearing assessment and CIHL severity grading, and use of trial designs that are well-informed by preclinical models and suitable for relatively small sample sizes. Increasing interest has made available new funding opportunities for expanding this urgently needed research

Food assistance is associated with improved body mass index, food security and attendance at clinic in an HIV program in central Haiti: a prospective observational cohort study

<p>Abstract</p> <p>Background</p> <p>Few data are available to guide programmatic solutions to the overlapping problems of undernutrition and HIV infection. We evaluated the impact of food assistance on patient outcomes in a comprehensive HIV program in central Haiti in a prospective observational cohort study.</p> <p>Methods</p> <p>Adults with HIV infection were eligible for monthly food rations if they had any one of: tuberculosis, body mass index (BMI) <18.5kg/m², CD4 cell count <350/mm³(in the prior 3 months) or severe socio-economic conditions. A total of 600 individuals (300 eligible and 300 ineligible for food assistance) were interviewed before rations were distributed, at 6 months and at 12 months. Data collected included demographics, BMI and food insecurity score (range 0 - 20).</p> <p>Results</p> <p>At 6- and 12-month time-points, 488 and 340 subjects were eligible for analysis. Multivariable analysis demonstrated that at 6 months, food security significantly improved in those who received food assistance versus who did not (-3.55 vs -0.16; P < 0.0001); BMI decreased significantly less in the food assistance group than in the non-food group (-0.20 vs -0.66; P = 0.020). At 12 months, food assistance was associated with improved food security (-3.49 vs -1.89, P = 0.011) and BMI (0.22 vs -0.67, P = 0.036). Food assistance was associated with improved adherence to monthly clinic visits at both 6 (P < 0.001) and 12 months (P = 0.033).</p> <p>Conclusions</p> <p>Food assistance was associated with improved food security, increased BMI, and improved adherence to clinic visits at 6 and 12 months among people living with HIV in Haiti and should be part of routine care where HIV and food insecurity overlap.</p

First Detection and Modeling of Spatially Resolved Lyα\alpha in TW Hya

Lyman-$\alpha$ (Ly$\alpha$) is the strongest emission line in UV spectra from T-Tauri stars. Due to its resonant nature, Ly$\alpha$ emission carries information about the physical properties of the H I medium via the scattering process. This work presents spatially resolved Ly$\alpha$ emission across a protoplanetary disk in the iconic face-on T-Tauri star TW Hya, observed with HST-STIS at spatial offsets 0$''$, $\pm 0.2''$, and $\pm 0.4''$. To comprehensively interpret these Ly$\alpha$ spectra, we utilize a 3D Monte-Carlo radiative transfer simulation in a wind-disk geometry. Successfully reproducing the observed spectra requires scattering contributions from both the wind and the H I disk. We constrain the properties of the wind, the H I column density ($\sim 10^{20} \rm cm^{-2}$) and the outflow velocity ($\sim 200 \rm km s^{-1}$). To reproduce the observed spatial distribution of Ly$\alpha$, we find that the wind must cover the H I disk when viewed face-on. Furthermore, to explore the effect of Ly$\alpha$ radiative transfer in T-Tauri stars, we compute the radiation field within the scattering medium and reveal that the wind reflection causes more Ly$\alpha$ photons to penetrate the disk. We also show the dependence between the disk inclination angle and the spatially resolved Ly$\alpha$ spectra. Understanding the role of Ly$\alpha$ emission in T-Tauri stars is pivotal for decoding the complex interactions between the winds, protoplanetary disks, and surrounding environments, which can significantly impact the chemistry in the protoplanetary disk. Our observation and modeling of spatially resolved Ly$\alpha$ show the necessity of spatially resolved Ly$\alpha$ observation of a broad range of targets.Comment: 17 pages, 18 figures, Submitted to MNRA

Relating the Cosmological Constant and Supersymmetry Breaking in Warped Compactifications of IIB String Theory

It has been suggested that the observed value of the cosmological constant is related to the supersymmetry breaking scale M_{susy} through the formula Lambda \sim M_p^4 (M_{susy}/M_p)^8. We point out that a similar relation naturally arises in the codimension two solutions of warped space-time varying compactifications of string theory in which non-isotropic stringy moduli induce a small but positive cosmological constant.Comment: 7 pages, LaTeX, references added and minor changes made, (v3) map between deSitter and global cosmic brane solutions clarified, supersymmetry breaking discussion improved and references adde

Locally Localized Gravity Models in Higher Dimensions

We explore the possibility of generalizing the locally localized gravity model in five space-time dimensions to arbitrary higher dimensions. In a space-time with negative cosmological constant, there are essentially two kinds of higher-dimensional cousins which not only take an analytic form but also are free from the naked curvature singularity in a whole bulk space-time. One cousin is a trivial extension of five-dimensional model, while the other one is in essence in higher dimensions. One interesting observation is that in the latter model, only anti-de Sitter ($AdS_p$) brane is physically meaningful whereas de Sitter ($dS_p$) and Minkowski ($M_p$) branes are dismissed. Moreover, for $AdS_p$ brane in the latter model, we study the property of localization of various bulk fields on a single brane. In particular, it is shown that the presence of the brane cosmological constant enables bulk gauge field and massless fermions to confine to the brane only by a gravitational interaction. We find a novel relation between mass of brane gauge field and the brane cosmological constant.Comment: 20 pages, LaTex 2e, revised version (to appear in Phys. Rev. D

Bosonic Fields in the String-like Defect Model

We study localization of bosonic bulk fields on a string-like defect with codimension 2 in a general space-time dimension in detail. We show that in cases of spin 0 scalar and spin 1 vector fields there are an infinite number of massless Kaluza-Klein (KK) states which are degenerate with respect to the radial quantum number, but only the massless zero mode state among them is coupled to fermion on the string-like defect. It is also commented on interesting extensions of the model at hand to various directions such as 'little' superstring theory, conformal field theory and a supersymmetric construction.Comment: 17 pages, LaTex 2e, revised version (to appear in Phys. Rev. D

Relaxation Response Induces Temporal Transcriptome Changes in Energy Metabolism, Insulin Secretion and Inflammatory Pathways

The relaxation response (RR) is the counterpart of the stress response. Millennia-old practices evoking the RR include meditation, yoga and repetitive prayer. Although RR elicitation is an effective therapeutic intervention that counteracts the adverse clinical effects of stress in disorders including hypertension, anxiety, insomnia and aging, the underlying molecular mechanisms that explain these clinical benefits remain undetermined. To assess rapid time-dependent (temporal) genomic changes during one session of RR practice among healthy practitioners with years of RR practice and also in novices before and after 8 weeks of RR training, we measured the transcriptome in peripheral blood prior to, immediately after, and 15 minutes after listening to an RR-eliciting or a health education CD. Both short-term and long-term practitioners evoked significant temporal gene expression changes with greater significance in the latter as compared to novices. RR practice enhanced expression of genes associated with energy metabolism, mitochondrial function, insulin secretion and telomere maintenance, and reduced expression of genes linked to inflammatory response and stress-related pathways. Interactive network analyses of RR-affected pathways identified mitochondrial ATP synthase and insulin (INS) as top upregulated critical molecules (focus hubs) and NF-κB pathway genes as top downregulated focus hubs. Our results for the first time indicate that RR elicitation, particularly after long-term practice, may evoke its downstream health benefits by improving mitochondrial energy production and utilization and thus promoting mitochondrial resiliency through upregulation of ATPase and insulin function. Mitochondrial resiliency might also be promoted by RR-induced downregulation of NF-κB-associated upstream and downstream targets that mitigates stress