The yellow fever virus (YFV) epidemic in Brazil is the largest in decades. The recent discovery of YFV in Brazilian
species mosquitos highlights a need to monitor the risk of reestablishment of urban ...YFV transmission in the Americas. We use a suite of epidemiological, spatial, and genomic approaches to characterize YFV transmission. We show that the age and sex distribution of human cases is characteristic of sylvatic transmission. Analysis of YFV cases combined with genomes generated locally reveals an early phase of sylvatic YFV transmission and spatial expansion toward previously YFV-free areas, followed by a rise in viral spillover to humans in late 2016. Our results establish a framework for monitoring YFV transmission in real time that will contribute to a global strategy to eliminate future YFV epidemics.
Despite great progress in curing childhood acute lymphoblastic leukemia (ALL), survival after relapse remains poor. We analyzed survival after relapse among 9585 pediatric patients enrolled on ...Children's Oncology Group clinical trials between 1988 and 2002. A total of 1961 patients (20.5%) experienced relapse at any site. The primary end point was survival. Patients were subcategorized by the site of relapse and timing of relapse from initial diagnosis. Time to relapse remains the strongest predictor of survival. Patients experiencing early relapse less than 18 months from initial diagnosis had a particularly poor outcome with a 5-year survival estimate of 21.0+/-1.8%. Standard risk patients who relapsed had improved survival compared with their higher risk counterparts; differences in survival for the two risk groups was most pronounced for patients relapsing after 18 months. Adjusting for both time and relapse site, multivariate analysis showed that age (10+ years) and the presence of central nervous system disease at diagnosis, male gender, and T-cell disease were significant predictors of inferior post-relapse survival. It can be noted that there was no difference in survival rates for relapsed patients in earlier vs later era trials. New therapeutic strategies are urgently needed for children with relapsed ALL and efforts should focus on discovering the biological pathways that mediate drug resistance.
Current strategies to treat pediatric acute lymphoblastic leukemia rely on risk stratification algorithms using categorical data. We investigated whether using continuous variables assigned different ...weights would improve risk stratification. We developed and validated a multivariable Cox model for relapse-free survival (RFS) using information from 21199 patients. We constructed risk groups by identifying cutoffs of the COG Prognostic Index (PI
) that maximized discrimination of the predictive model. Patients with higher PI
have higher predicted relapse risk. The PI
reliably discriminates patients with low vs. high relapse risk. For those with moderate relapse risk using current COG risk classification, the PI
identifies subgroups with varying 5-year RFS. Among current COG standard-risk average patients, PI
identifies low and intermediate risk groups with 96% and 90% RFS, respectively. Similarly, amongst current COG high-risk patients, PI
identifies four groups ranging from 96% to 66% RFS, providing additional discrimination for future treatment stratification. When coupled with traditional algorithms, the novel PI
can more accurately risk stratify patients, identifying groups with better outcomes who may benefit from less intensive therapy, and those who have high relapse risk needing innovative approaches for cure.
Over the past 3 decades the Arctic has seen substantial warming. Previous local to regional scale studies have shown a considerable reduction in the size of lakes in this region. The subsequent ...exposure of carbon‐ and methane‐rich sediments and the direct changes in surface albedo feed back into the drivers of regional and global climate change. Understanding and quantifying changes in the Arctic is a critical component of climate modeling due to the cooling effect of the Arctic on the global climate. The current work utilizes global satellite data from the Moderate Resolution Imaging Spectro‐radiometer (MODIS) instrument to investigate changes in lakes across Canada between 2000 and 2009. The results show a net reduction of more than 6,700 km2 in the surface area of water in lakes across Canada. Modest gains in the southern regions are offset by larger losses in surface area farther north. Additionally, spatial analysis shows that the lakes showing change are clustered in groups. This suggests that local variability may play a role in the observed changes. Further work is needed to extend the analysis to the circumpolar Arctic.
Key Points
Arctic lakes are numerous and are changing
Changes are greater and more widespread than previous studies indicate
Changes can be seen using moderate resolution remote sensing
Remission induction therapy for acute lymphoblastic leukemia (ALL) includes medications that may cause hepatotoxicity, including asparaginase. We used a genome‐wide association study to identify loci ...associated with elevated alanine transaminase (ALT) levels after induction therapy in children with ALL enrolled on St. Jude Children's Research Hospital (SJCRH) protocols. Germline DNA was genotyped using arrays and exome sequencing. Adjusting for age, body mass index, ancestry, asparaginase preparation, and dosage, the PNPLA3 rs738409 (C>G) I148M variant, previously associated with fatty liver disease risk, had the strongest genetic association with ALT (P = 2.5 × 10‐8). The PNPLA3 rs738409 variant explained 3.8% of the variability in ALT, and partly explained race‐related differences in ALT. The PNPLA3 rs738409 association was replicated in an independent cohort of 2,285 patients treated on Children's Oncology Group protocol AALL0232 (P = 0.024). This is an example of a pharmacogenetic variant overlapping with a disease risk variant.
A tale of two clades: monkeypox viruses Likos, Anna M; Sammons, Scott A; Olson, Victoria A ...
Journal of general virology,
10/2005, Letnik:
86, Številka:
10
Journal Article
Recenzirano
Odprti dostop
1 National Center for Infectious Disease, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop G43, Atlanta, GA 30333, USA
2 World Health Organization, Geneva, Switzerland
...Correspondence Inger K. Damon iad7{at}cdc.gov
Human monkeypox was first recognized outside Africa in 2003 during an outbreak in the USA that was traced to imported monkeypox virus (MPXV)-infected West African rodents. Unlike the smallpox-like disease described in the Democratic Republic of the Congo (DRC; a Congo Basin country), disease in the USA appeared milder. Here, analyses compared clinical, laboratory and epidemiological features of confirmed human monkeypox case-patients, using data from outbreaks in the USA and the Congo Basin, and the results suggested that human disease pathogenicity was associated with the viral strain. Genomic sequencing of USA, Western and Central African MPXV isolates confirmed the existence of two MPXV clades. A comparison of open reading frames between MPXV clades permitted prediction of viral proteins that could cause the observed differences in human pathogenicity between these two clades. Understanding the molecular pathogenesis and clinical and epidemiological properties of MPXV can improve monkeypox prevention and control.
Published online ahead of print on 25 July 2005 as DOI 10.1099/vir.0.81215-0.
The GenBank/EMBL/DDBJ accession numbers for the sequences reported in this paper are DQ011153 DQ011157 .
Supplementary material is available in JGV Online.
These authors contributed equally to this work.
Advancing technologies of the corn dry-milling ethanol production process includes the mechanical separation of fiber containing particles from a portion of plant and yeast based nitrogenous ...particles. The resulting high protein processed corn coproduct (HPCoP) contains approximately 52% CP, 36% NDF, 6.4% total fatty acids. The objective of this experiment was to examine the effects of replacing non-enzymatically browned soybean meal with the HPCoP on DMI, energy and N utilization, and milk production of lactating Jersey cows. Twelve multiparous Jersey cows were utilized in a triplicated 4x4 Latin square design consisting of 4, 28 d periods. Cows were blocked by milk yield and assigned randomly to 1 of 4 treatment diets that contained HPCoP (DM basis) at (1) 0% (00CTRL); (2) 2.6% (2.6L); (3) 5.4% (5.4M); and (4) 8.0% (8.0H). Diets were formulated to be isonitrogenous and thus replace non-enzymatically browned soybean meal with HPCoP in the concentrate mix while forage inclusion remained the same across diets. Increasing the concentration of HPCoP had no effect on dry matter intake (averaging 19.9 ± 0.62 kg/d), but tended to linearly increase milk yield (27.8, 28.5, 29.8, and 29.0 ± 1.00 kg/d). While no difference was observed in the concentration of milk protein with increasing inclusion of HPCoP (3.40 ± 0.057%), the concentration of fat linearly increased with the inclusion of HPCoP (5.05, 5.19, 5.15, 5.47 ± 0.18%). No differences were observed in the digestibility of dry matter, neutral detergent fiber, crude protein, total fatty acids, and gross energy averaging 66.6 ± 0.68%, 49.0 ± 1.03%, 66.1 ± 0.82%, 73.6 ± 1.73%, 66.3 ± 0.72%, respectively with increasing HPCoP inclusion. The concentration of dietary gross energy linearly increased with increasing concentrations of HPCoP (4.25, 4.26, 4.28, and 4.31 ± 0.01 Mcal/kg), but no difference was observed in digestible energy and metabolizable energy (ME) across treatments averaging 2.83 ± 0.033 and 2.53 ± 0.043 Mcal/kg, respectively. Concentration of dietary net energy for lactation (NEL) tended to increase with increasing HPCoP (1.61, 1.72, 1.74, 1.72 ± 0.054 Mcal/kg) with the ratio of NEL:ME increasing linearly with increasing HPCoP inclusion (0.648, 0.676, 0.687, 0.677 ± 0.0124). Results of this study suggest that inclusion of the HPCoP can replace non-enzymatically browned soybean meal and support normal milk production.
Very high resolution (VHR) satellite data is experiencing rapid annual growth, producing petabytes of remotely sensed data per year. The WorldView constellation, operated by DigitalGlobe, images over ...1.2billionkm2 annually at <2m spatial resolution. Due to computation, data cost, and methodological concerns, VHR satellite data has mainly been used to produce needed geospatial information for site-specific phenomena. This project produced a VHR spatiotemporally explicit wall-to-wall cropland area map for the rainfed residential cropland mosaic of the Tigray Region, Ethiopia, which is comprised mostly of smallholder farms. Moderate resolution satellite data do not have adequate spatial resolution to capture the total area occupied by smallholder farms, i.e., farms with agricultural fields of ≤45×45m in dimension. In order to accurately map smallholder cropped area over a large region, hundreds of VHR images spanning two or more years are needed. Sub-meter WorldView-1 and WorldView-2 segmentation results were combined with median phenology amplitude from Landsat 8 data to map cropped area. Over 2700 VHR WorldView-1, -2 data were obtained from the U.S. National Geospatial-Intelligence Agency (NGA) via the NextView license agreement and were processed from raw imagery to produce a smallholder crop map in ~1week using a semi-automated method with the large computing capacity of the Advanced Data Analytics Platform. We estimated cropped area in Tigray to be 46% with a commission error of 5%±10% and omission error of 15%±12%. This methodology is extensible to other regions with similar vegetation texture and can easily be expanded to run on much larger regions.
•First very high resolution wall-to-wall smallholder crop area for Tigray, Ethiopia•Semi-automated segmentation of over 40TB of WorldView-1 and WorldView-2 images•Timely big data processing on NASA Advanced Data Analytics Platform (ADAPT)•Results show 46% of area is smallholder croplands where field sizes are ≤1ha.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive motor neuron loss, with additional pathophysiological involvement of non-neuronal cells such as ...microglia. The commonest ALS-associated genetic variant is a hexanucleotide repeat expansion (HRE) mutation in C9orf72. Here, we study its consequences for microglial function using human iPSC-derived microglia. By RNA-sequencing, we identify enrichment of pathways associated with immune cell activation and cyto-/chemokines in C9orf72 HRE mutant microglia versus healthy controls, most prominently after LPS priming. Specifically, LPS-primed C9orf72 HRE mutant microglia show consistently increased expression and release of matrix metalloproteinase-9 (MMP9). LPS-primed C9orf72 HRE mutant microglia are toxic to co-cultured healthy motor neurons, which is ameliorated by concomitant application of an MMP9 inhibitor. Finally, we identify release of dipeptidyl peptidase-4 (DPP4) as a marker for MMP9-dependent microglial dysregulation in co-culture. These results demonstrate cellular dysfunction of C9orf72 HRE mutant microglia, and a non-cell-autonomous role in driving C9orf72-ALS pathophysiology in motor neurons through MMP9 signaling.
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