Description: Purpose: While extent of tumor resection is an important predictor of outcome in glioma, margin delineation remains challenging due to lack of inherent contrast between tumor and normal parenchyma. Fluorescence-guided surgery is promising for its ability to enhance contrast through exogenous fluorophores; however, the specificity and sensitivity of the underlying contrast mechanism and tumor delivery and uptake vary widely across approved and emerging agents. Experimental Design: Rats with orthotopic F98 wild-type and F98 EGFR-positive (EGFR + ) gliomas received in vivo administration of IRDye680RD, 5-aminioleuvulinic acid, and ABY-029—markers of perfusion, protoporphyrin metabolism, and EGFR expression, respectively. Ex vivo imaging demonstrates the contrast mechanism–dependent spatial heterogeneity and enables within-animal comparisons of tumor-to-background ratio (TBR). Results: Generally, ABY-029 outperformed PpIX in F98 EGFR orthotopic tumor margins and core (50% and 60% higher TBR, respectively). PpIX outperformed ABY-029 in F98 wt margins by 60% but provided equivalent contrast in the bulk tumor. IRDye680RD provided little contrast, having an average TBR of 1.7 ± 0.2. The unique spatial patterns of each agent were combined into a single metric, the multimechanistic fluorescence-contrast index (MFCI). ABY-029 performed best in EGFR + tumors (91% accuracy), while PpIX performed best in wild-type tumors (87% accuracy). Across all groups, ABY-029 and PpIX performed similarly (80% and 84%, respectively) but MFCI was 91% accurate, supporting multiagent imaging when tumor genotype was unknown. Conclusions: Human use of ABY-029 for glioma resection should enhance excision of EGFR + tumors and could be incorporated into current PpIX strategies to further enhance treatment in the general glioma case. Clin Cancer Res; 23(9); 2203–12. ©2016 AACR .

Description: Phase variation (random ON/OFF switching) of gene expression is a common feature of host-adapted pathogenic bacteria. Phase variably expressed N 6 -adenine DNA methyltransferases (Mod) alter global methylation patterns resulting in changes in gene expression. These systems constitute phase variable regulons called phasevarions. Neisseria meningitidis phasevarions regulate genes including virulence factors and vaccine candidates, and alter phenotypes including antibiotic resistance. The target site recognized by these Type III N 6 -adenine DNA methyltransferases is not known. Single molecule, real-time (SMRT) methylome analysis was used to identify the recognition site for three key N. meningitidis methyltransferases: ModA11 (exemplified by M.NmeMC58I) (5'-CGY m6 A G-3'), ModA12 (exemplified by M.Nme77I, M.Nme18I and M.Nme579II) (5'-AC m6 A CC-3') and ModD1 (exemplified by M.Nme579I) (5'-CC m6 A GC-3'). Restriction inhibition assays and mutagenesis confirmed the SMRT methylome analysis. The ModA11 site is complex and atypical and is dependent on the type of pyrimidine at the central position, in combination with the bases flanking the core recognition sequence 5'-CGY m6 A G-3'. The observed efficiency of methylation in the modA11 strain (MC58) genome ranged from 4.6% at 5'-GCGC m6 A GG-3' sites, to 100% at 5'-ACGT m6 A GG-3' sites. Analysis of the distribution of modified sites in the respective genomes shows many cases of association with intergenic regions of genes with altered expression due to phasevarion switching.

Description: Author(s): Mario Pitschmann, Chien-Yeah Seng, Craig D. Roberts, and Sebastian M. Schmidt A symmetry-preserving Dyson-Schwinger equation treatment of a vector-vector contact interaction is used to compute dressed-quark-core contributions to the nucleon σ-term and tensor charges. The latter enable one to directly determine the effect of dressed-quark electric dipole moments (EDMs) on neut... [Phys. Rev. D 91, 074004] Published Fri Apr 03, 2015

Description: Author(s): Chao Shi, Chen Chen, Lei Chang, Craig D. Roberts, Sebastian M. Schmidt, and Hong-Shi Zong We compute all kaon and pion parton distribution amplitudes (PDAs) to twist three and find that only the pseudotensor PDA can reasonably be approximated by its conformal limit expression. At terrestrially accessible energy scales, the twist-two and pseudoscalar twist-three PDAs differ significantly … [Phys. Rev. D 92, 014035] Published Thu Jul 30, 2015

Description: Background: Globally, countries are increasingly prioritizing the reduction of health inequalities and provision of universal health coverage. While national benchmarking has become more common, such work at subnational levels is rare. The timely and rigorous measurement of local levels and trends in key health interventions and outcomes is vital to identifying areas of progress and detecting early signs of stalled or declining health system performance. Previous studies have yet to provide a comprehensive assessment of Uganda’s maternal and child health (MCH) landscape at the subnational level. Methods: By triangulating a number of different data sources – population censuses, household surveys, and administrative data – we generated regional estimates of 27 key MCH outcomes, interventions, and socioeconomic indicators from 1990 to 2011. After calculating source-specific estimates of intervention coverage, we used a two-step statistical model involving a mixed-effects linear model as an input to Gaussian process regression to produce regional-level trends. We also generated national-level estimates and constructed an indicator of overall intervention coverage based on the average of 11 high-priority interventions. Results: National estimates often veiled large differences in coverage levels and trends across Uganda’s regions. Under-5 mortality declined dramatically, from 163 deaths per 1,000 live births in 1990 to 85 deaths per 1,000 live births in 2011, but a large gap between Kampala and the rest of the country persisted. Uganda rapidly scaled up a subset of interventions across regions, including household ownership of insecticide-treated nets, receipt of artemisinin-based combination therapies among children under 5, and pentavalent immunization. Conversely, most regions saw minimal increases, if not actual declines, in the coverage of indicators that required multiple contacts with the health system, such as four or more antenatal care visits, three doses of oral polio vaccine, and two doses of intermittent preventive therapy during pregnancy. Some of the regions with the lowest levels of overall intervention coverage in 1990, such as North and West Nile, saw marked progress by 2011; nonetheless, sizeable disparities remained between Kampala and the rest of the country. Countrywide, overall coverage increased from 40 % in 1990 to 64 % in 2011, but coverage in 2011 ranged from 57 % to 70 % across regions. Conclusions: The MCH landscape in Uganda has, for the most part, improved between 1990 and 2011. Subnational benchmarking quantified the persistence of geographic health inequalities and identified regions in need of additional health systems strengthening. The tracking and analysis of subnational health trends should be conducted regularly to better guide policy decisions and strengthen responsiveness to local health needs.

Description: Author(s): Jorge Segovia, Bruno El-Bennich, Eduardo Rojas, Ian C. Cloët, Craig D. Roberts, Shu-Sheng Xu, and Hong-Shi Zong We employ a continuum approach to the three valence-quark bound-state problem in relativistic quantum field theory to predict a range of properties of the proton’s radial excitation and thereby unify them with those of numerous other hadrons. Our analysis indicates that the nucleon’s first radial ex… [Phys. Rev. Lett. 115, 171801] Published Wed Oct 21, 2015

Description: Journal of Medicinal Chemistry DOI: 10.1021/acs.jmedchem.5b00948

Description: Any wildfire generates ash, the solid residue derived from burning biomass. Vegetation fire ash consists of charred organic material, charcoal, and inorganic mineral substances. Recent studies identified ash deposits as a dual system: soil and ash strata. The addition of ash to the soil profile alters soil properties and dynamics. A thorough analysis of ash-soil profile reveals a structural appearance of thin laminas. The laminas differ in a variety of physical properties and mineral composition. This research aims at assessing the unique properties of ash-soil profiles by performing an infrared spectroscopic study and statistical analysis. For that purpose, several laboratory experiments were conducted. The paper presents semi-quantitative results of spectral analysis calculated by four statistical methods. The results indicate a well-established laminar structure of the ash and evaluate the characteristics of each lamina. The proposed methodology was examined under real-world conditions; a field experiment of 2 m 2 parcel with in-situ O horizon was flamed and burned-out. The field samples illustrated the formation of micro-laminas, which proved to be similar to the laboratory samples. This detailed approach may promote a better understanding of the complex nature to the ash, the ash-soil interactions and its effect on the edaphic ecosystem.

Description: Introduction To interrupt malaria transmission, strategies must target the parasite reservoir in both humans and mosquitos. Testing of community members linked to an index case, termed reactive case detection (RACD), is commonly implemented in low transmission areas, though its impact may be limited by the sensitivity of current diagnostics. Indoor residual spraying (IRS) before malaria season is a cornerstone of vector control efforts. Despite their implementation in Namibia, a country approaching elimination, these methods have been met with recent plateaus in transmission reduction. This study evaluates the effectiveness and feasibility of two new targeted strategies, reactive focal mass drug administration (rfMDA) and reactive focal vector control (RAVC) in Namibia. Methods and analysis This is an open-label cluster randomised controlled trial with 2 x 2 factorial design. The interventions include: rfMDA (presumptive treatment with artemether-lumefantrine (AL)) versus RACD (rapid diagnostic testing and treatment using AL) and RAVC (IRS with Acellic 300CS) versus no RAVC. Factorial design also enables comparison of the combined rfMDA+RAVC intervention to RACD. Participants living in 56 enumeration areas will be randomised to one of four arms: rfMDA, rfMDA+RAVC, RACD or RACD+RAVC. These interventions, triggered by index cases detected at health facilities, will be targeted to individuals residing within 500 m of an index. The primary outcome is cumulative incidence of locally acquired malaria detected at health facilities over 1 year. Secondary outcomes include seroprevalence, infection prevalence, intervention coverage, safety, acceptability, adherence, cost and cost-effectiveness. Ethics and dissemination Findings will be reported on clinicaltrials.gov, in peer-reviewed publications and through stakeholder meetings with MoHSS and community leaders in Namibia. Trial registration number NCT02610400; Pre-results.

Description: Biochemistry DOI: 10.1021/acs.biochem.6b01139