Stratification of malaria incidence in Papua New Guinea (2011-2019): contribution towards a sub-national control policy

Malaria risk in Papua New Guinea (PNG) is highly heterogeneous, between and within geographical regions, which is operationally challenging for control. To enhance targeting of malaria interventions in PNG, we investigated risk factors and stratified malaria incidence at the level of health facility catchment areas. Catchment areas and populations of 808 health facilities were delineated using a travel-time accessibility approach and linked to reported malaria cases (2011-2019). Zonal statistics tools were used to calculate average altitude and air temperature in catchment areas before they were spatially joined with incidence rates. In addition, empirical Bayesian kriging (EBK) was employed to interpolate incidence risk strata across PNG. Malaria annual incidence rates are, on average, 186.3 per 1000 population in catchment areas up to 600 m, dropped to 98.8 at (800-1400) m, and to 24.1 cases above 1400 m altitude. In areas above the two altitudinal thresholds 600m and 1400m, the average annual temperature drops below 22°C and 17°C, respectively. EBK models show very low- to low-risk strata ( 200 per 1000) strata are modelled mainly in Momase and Islands Regions. Besides, strata with moderate risk (100-200) predominate throughout the coastal areas. While 35.7% of the PNG population (estimated 3.33 million in 2019) lives in places at high or moderate risk of malaria, 52.2% (estimated 4.88 million) resides in very low-risk areas. In five provinces, relatively large proportions of populations (> 50%) inhabit high-risk areas: New Ireland, East and West New Britain, Sandaun and Milne Bay. Incidence maps show a contrast in malaria risk between coastal and inland areas influenced by altitude. However, the risk is highly variable in low-lying areas. Malaria interventions should be guided by sub-national risk levels in PNG

SpotXplore: a Cytoscape plugin for visual exploration of hotspot expression in gene regulatory networks

Summary: SpotXplore is a plugin for Cytoscape for extraction and visualization of differentially expressed subnetworks (hotspots) from gene networks. The hotspot-based visualization approach enables interactive exploration of regulatory interactions in differentially expressed gene sets, and it allows a researcher to explore gene expression in direct relation to the affected cellular gene network. The hotspots provide a view beyond the commonly used metabolic pathways and gene ontologies

How Human Brucellosis Incidence in Urban Kampala Can Be Reduced Most Efficiently? A Stochastic Risk Assessment of Informally-Marketed Milk

In Kampala, Uganda, studies have shown a significant incidence of human brucellosis. A stochastic risk assessment involving two field surveys (cattle farms and milk shops) and a medical record survey was conducted to assess the risk of human brucellosis infection through consumption of informally marketed raw milk potentially infected with Brucella abortus in Kampala and to identify the best control options.In the cattle farm survey, sera of 425 cows in 177 herds in the Kampala economic zone were sampled and tested for brucellosis using a competitive enzyme-linked immunosorbent assay (CELISA). Farmers were interviewed for dairy information. In the milk shop surveys, 135 milk sellers in the urban areas were interviewed and 117 milk samples were collected and tested using an indirect enzyme-linked immunosorbent assay (IELISA). A medical record survey was conducted in Mulago National Referral Hospital for serological test results. A risk model was developed synthesizing data from these three surveys. Possible control options were prepared based on the model and the reduction of risk was simulated for each scenario. Overall, 12.6% (6.8-18.9: 90%CI) of informally marketed milk in urban Kampala was contaminated with B.abortus at purchase and the annual incidence rate was estimated to be 5.8 (90% CI: 5.3-6.2) per 10,000 people. The best control option would be the construction of a milk boiling centre either in Mbarara, the largest source of milk, or in peri-urban Kampala and to ensure that milk traders always sell milk to the boiling centre; 90% success in enforcing these two options would reduce risk by 47.4% (21.6-70.1: 90%CI) and 82.0% (71.0-89.0: 90%CI), respectively.This study quantifies the risk of human brucellosis infection through informally marketed milk and estimates the incidence rate in Kampala for the first time; risk-based mitigation strategies are outlined to assist in developing policy

Extreme Magnification Microlensing Event OGLE-2008-BLG-279: Strong Limits on Planetary Companions to the Lens Star

We analyze the extreme high-magnification microlensing event OGLE-2008-BLG-279, which peaked at a maximum magnification of A ~ 1600 on 30 May 2008. The peak of this event exhibits both finite-source effects and terrestrial parallax, from which we determine the mass of the lens, M_l=0.64 +/- 0.10 M_Sun, and its distance, D_l = 4.0 +/- 0.6. We rule out Jupiter-mass planetary companions to the lens star for projected separations in the range 0.5-20 AU. More generally, we find that this event was sensitive to planets with masses as small as 0.2 M_Earth ~= 2 M_Mars with projected separations near the Einstein ring (~3 AU).Comment: 25 pages, 7 figures, submitted to Ap

Frequency of Solar-Like Systems and of Ice and Gas Giants Beyond the Snow Line from High-Magnification Microlensing Events in 2005-2008

We present the first measurement of planet frequency beyond the "snow line" for planet/star mass-ratios[-4.5<log q<-2]: d^2 N/dlog q/dlog s=(0.36+-0.15)/dex^2 at mean mass ratio q=5e-4, and consistent with being flat in log projected separation, s. Our result is based on a sample of 6 planets detected from intensive follow-up of high-mag (A>200) microlensing events during 2005-8. The sample host stars have typical mass M_host 0.5 Msun, and detection is sensitive to planets over a range of projected separations (R_E/s_max,R_E*s_max), where R_E 3.5 AU sqrt(M_host/Msun) is the Einstein radius and s_max (q/5e-5)^{2/3}, corresponding to deprojected separations ~3 times the "snow line". Though frenetic, the observations constitute a "controlled experiment", which permits measurement of absolute planet frequency. High-mag events are rare, but the high-mag channel is efficient: half of high-mag events were successfully monitored and half of these yielded planet detections. The planet frequency derived from microlensing is a factor 7 larger than from RV studies at factor ~25 smaller separations [2<P<2000 days]. However, this difference is basically consistent with the gradient derived from RV studies (when extrapolated well beyond the separations from which it is measured). This suggests a universal separation distribution across 2 dex in semi-major axis, 2 dex in mass ratio, and 0.3 dex in host mass. Finally, if all planetary systems were "analogs" of the Solar System, our sample would have yielded 18.2 planets (11.4 "Jupiters", 6.4 "Saturns", 0.3 "Uranuses", 0.2 "Neptunes") including 6.1 systems with 2 or more planet detections. This compares to 6 planets including one 2-planet system in the actual sample, implying a first estimate of 1/6 for the frequency of solar-like systems.Comment: 42 pages, 10 figure

Experimental determination of translational start sites resolves uncertainties in genomic open reading frame predictions – application to Mycobacterium tuberculosis

Correct identification of translational start sites is important for understanding protein function and transcriptional regulation. The annotated translational start sites contained in genome databases are often predicted using bioinformatics and are rarely verified experimentally, and so are not all accurate. Therefore, we devised a simple approach for determining translational start sites using a combination of epitope tagging and frameshift mutagenesis. This assay was used to determine the start sites of three Mycobacterium tuberculosis proteins: LexA, SigC and Rv1955. We were able to show that proteins may begin before or after the predicted site. We also found that a small, non-annotated open reading frame upstream of Rv1955 was expressed as a protein, which we have designated Rv1954A. This approach is readily applicable to any bacterial species for which plasmid transformation can be achieved

Extracellular nanovesicles for packaging of CRISPR-Cas9 protein and sgRNA to induce therapeutic exon skipping

Prolonged expression of the CRISPR-Cas9 nuclease and gRNA from viral vectors may cause off-target mutagenesis and immunogenicity. Thus, a transient delivery system is needed for therapeutic genome editing applications. Here, we develop an extracellular nanovesicle-based ribonucleoprotein delivery system named NanoMEDIC by utilizing two distinct homing mechanisms. Chemical induced dimerization recruits Cas9 protein into extracellular nanovesicles, and then a viral RNA packaging signal and two self-cleaving riboswitches tether and release sgRNA into nanovesicles. We demonstrate efficient genome editing in various hard-to-transfect cell types, including human induced pluripotent stem (iPS) cells, neurons, and myoblasts. NanoMEDIC also achieves over 90% exon skipping efficiencies in skeletal muscle cells derived from Duchenne muscular dystrophy (DMD) patient iPS cells. Finally, single intramuscular injection of NanoMEDIC induces permanent genomic exon skipping in a luciferase reporter mouse and in mdx mice, indicating its utility for in vivo genome editing therapy of DMD and beyond

MOA-2009-BLG-387Lb: A massive planet orbiting an M dwarf

We report the discovery of a planet with a high planet-to-star mass ratio in the microlensing event MOA-2009-BLG-387, which exhibited pronounced deviations over a 12-day interval, one of the longest for any planetary event. The host is an M dwarf, with a mass in the range 0.07 M_sun < M_host < 0.49M_sun at 90% confidence. The planet-star mass ratio q = 0.0132 +- 0.003 has been measured extremely well, so at the best-estimated host mass, the planet mass is m_p = 2.6 Jupiter masses for the median host mass, M = 0.19 M_sun. The host mass is determined from two "higher order" microlensing parameters. One of these, the angular Einstein radius \theta_E = 0.31 +- 0.03 mas, is very well measured, but the other (the microlens parallax \pi_E, which is due to the Earth's orbital motion) is highly degenate with the orbital motion of the planet. We statistically resolve the degeneracy between Earth and planet orbital effects by imposing priors from a Galactic model that specifies the positions and velocities of lenses and sources and a Kepler model of orbits. The 90% confidence intervals for the distance, semi-major axis, and period of the planet are 3.5 kpc < D_L < 7.9 kpc, 1.1 AU < a < 2.7AU, and 3.8 yr < P < 7.6 yr, respectively.Comment: 20 pages including 8 figures. A&A 529 102 (2011