Avian GIS models signal human risk for West Nile virus in Mississippi

BACKGROUND: West Nile virus (WNV) poses a significant health risk for residents of Mississippi. Physicians and state health officials are interested in new and efficient methods for monitoring disease spread and predicting future outbreaks. Geographic Information Systems (GIS) models have the potential to support these efforts. Environmental conditions favorable for mosquito habitat were modeled using GIS to derive WNV risk maps for Mississippi. Variables important to WNV dissemination were selected and classified as static and dynamic. The static variables included road density, stream density, slope, and vegetation. The dynamic variable represented seasonal water budget and was calculated using precipitation and evaporation estimates. Significance tests provided deterministic evidence of variable importance to the models. RESULTS: Several models were developed to estimate WNV risk including a landscape-base model and seasonal climatic sub-models. P-values from t-tests guided variable importance ranking. Variables were ranked and weights assigned as follows: road density (0.4), stream density (0.3), slope (0.2) and vegetation (0.1). This landscape-base model was modified by climatic conditions to assess the importance of climate to WNV risk. Human case data at the zip code level were used to validate modeling results. All models were summarized by zip codes for interpretation and model validation. For all models, estimated risk was higher for zip codes with at least one human case than for zip codes where no human cases were recorded. Overall median measure of risk by zip code indicated that 67% of human cases occurred in the high-risk category. CONCLUSION: Modeling results indicated that dead bird occurrences are correlated with human WNV risk and can facilitate the assessment of environmental variables that contribute to that risk. Each variable's importance in GIS-based risk predictions was assigned deterministically. Our models indicated non-uniform distribution of risk across the state and showed elevated risk in urban and as well as rural areas. Model limitations include resolution of human data, zip code aggregation issues, and quality/availability of vegetation and stream density layers. Our approach verified that WNV risk can be modeled at the state level and can be modified for risk predictions of other vector-borne diseases in varied ecological regions

Giant segregation transition as origin of liquid metal embrittlement in the Fe-Zn system

A giant Zn segregation transition is revealed using CALPHAD-integrated density-based modelling of Zn segregation into Fe grain boundaries (GBs). The results show that above a threshold of only a few atomic percent Zn in the alloy, a substantial amount of up to 60 at.% Zn can segregate to the GB. We also found that the amount of segregation significantly increases with decreasing temperature, while the required Zn content in the alloy for triggering the segregation transition decreases. Direct evidence of this Zn segregation transition is obtained using high-resolution scanning transmission electron microscopy. We trace the origin of the segregation transition and its temperature dependence back to the low cohesive energy of Zn and a miscibility gap in Fe-Zn GB, arising from the magnetic ordering effect, which is demonstrated by ab initio calculations. We show that the massive Zn segregation resulting from the segregation transition greatly assists with liquid wetting and reduces the work of separation along the GB. These findings reveal the fundamental origin of GB weakening and therefore liquid metal embrittlement in the Fe-Zn system.Comment: Original work, Letter, 14 pages including supplementary material (SM), 8 figures (3 in SM), 2 tables in S

Influence of functionalized fullerene structure on polymer photovoltaic degradation

The time dependence of device performance has been measured for photocells using blends containing the conjugated polymer, poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV) with two different functionalized C60 electron acceptor molecules: commercially available [6,6]-phenyl C61 butyric acid methyl ester (PCBM) or [6,6]-phenyl C61 butyric acid octadecyl ester (PCBOD) produced in this laboratory. Performance was characterized by the short-circuit current output of the devices, with the time dependence of PCBM samples typically degrading exponentially. Variations in the characteristic lifetime of the devices were observed to depend on the molar fraction of the electron acceptor molecules (calculated with respect to the MEH-PPV monomer fraction). In comparison to the PCBM samples, the stability of the PCBOD blends was significantly enhanced, with a one or two order of magnitude improvement. Corresponding spectroscopic data with similar time evolution as the transport measurements suggest an independent means for determining and understanding degradation mechanisms

Type 1 Diabetes in the BB Rat: A Polygenic Disease

OBJECTIVE-Two type 1 diabetes susceptibility genes have been identified in the spontaneously diabetic biobreeding diabetes-prone (BBDP) rat, the major histocompatibility complex (MHC) (RT1) class II u haplotype (Iddm1) and Gimap5 (Iddm2). The strong effects of these have impeded previous efforts to map additional loci. We tested the hypothesis that type 1 diabetes is a polygenic disease in the BBDP rat. RESEARCH DESIGN AND METHODS-We performed the most comprehensive genome-wide linkage analysis for type 1 diabetes, age of disease onset (AOO), and insulitis subpheno- types in 574 F2 animals from a cross-intercross between BBDP and type 1 diabetes-resistant, double congenic ACI.BBDP- RT1u,Gimap5 (ACI.BB 1ulyp) rats, where both Iddm1 and Iddm2 were fixed as BBDP. RESULTS-A total of 19% of these F2 animals developed type 1 diabetes, and eight type 1 diabetes susceptibility loci were mapped, six showing significant linkage (chromosomes 1, 3, 6 [two loci], 12, and 14) and two (chromosomes 2 and 17) suggestive linkage. The chromosomes 6, 12, and 14 intervals were also linked to the severity of islet infiltration by immunocytes, while those on chromosomes 1, 6 (two loci), 14, 17, and a type 1 diabetes-unlinked chromosome 8 interval showed significant linkage to the degree of islet atrophy. Four loci exhibited suggestive linkage to AOO on chromosomes 2 (two loci), 7, and 18 but were unlinked to type 1 diabetes. INS, PTPN22, IL2/IL21, C1QTNF6, and C12orf30, associated with human type 1 diabetes, are contained within the chromosomes 1, 2, 7, and 12 loci. CONCLUSIONS-This study demonstrates that the BBDP diabetic syndrome is a complex, polygenic disease that may share additional susceptibility genes besides MHC class II with human type 1 diabetes

Application of a stochastic modeling to evaluate tuberculosis onset in patients treated with tumor necrosis factor inhibitors

In this manuscript we apply stochastic modeling to investigate the risk of reactivation of latent mycobacterial infections in patients undergoing treatment with tumor necrosis factor inhibitors. First, we review the perspective proposed by one of the authors in a previous work and which consists in predicting the occurrence of reactivation of latent tuberculosis infection or newly acquired tuberculosis during treatment; this is based on variational procedures on a simple set of parameters (e.g. rate of reactivation of a latent infection). Then, we develop a full analytical study of this approach through a Markov chain analysis and we find an exact solution for the temporal evolution of the number of cases of tuberculosis infection (re)activation. The analytical solution is compared with Monte Carlo simulations and with experimental data, showing overall excellent agreement. The generality of this theoretical framework allows to investigate also the case of non-tuberculous mycobacteria infections; in particular, we show that reactivation in that context plays a minor role. This may suggest that, while the screening for tuberculous is necessary prior to initiating biologics, when considering non-tuberculous mycobacteria only a watchful monitoring during the treatment is recommended. The framework outlined in this paper is quite general and could be extremely promising in further researches on drug-related adverse events.Comment: 26 pages, 7 figure

Mycobactericidal activity of sutezolid (PNU-100480) in sputum (EBA) and blood (WBA) of patients with pulmonary tuberculosis

Rationale: Sutezolid (PNU-100480) is a linezolid analog with superior bactericidal activity against Mycobacterium tuberculosis in the hollow fiber, whole blood and mouse models. Like linezolid, it is unaffected by mutations conferring resistance to standard TB drugs. This study of sutezolid is its first in tuberculosis patients. METHODS: Sputum smear positive tuberculosis patients were randomly assigned to sutezolid 600 mg BID (N = 25) or 1200 mg QD (N = 25), or standard 4-drug therapy (N = 9) for the first 14 days of treatment. Effects on mycobacterial burden in sputum (early bactericidal activity or EBA) were monitored as colony counts on agar and time to positivity in automated liquid culture. Bactericidal activity was also measured in ex vivo whole blood cultures (whole blood bactericidal activity or WBA) inoculated with M. tuberculosis H37Rv. RESULTS: All patients completed assigned treatments and began subsequent standard TB treatment according to protocol. The 90% confidence intervals (CI) for bactericidal activity in sputum over the 14 day interval excluded zero for all treatments and both monitoring methods, as did those for cumulative WBA. There were no treatment-related serious adverse events, premature discontinuations, or dose reductions due to laboratory abnormalities. There was no effect on the QT interval. Seven sutezolid-treated patients (14%) had transient, asymptomatic ALT elevations to 173±34 U/L on day 14 that subsequently normalized promptly; none met Hy's criteria for serious liver injury. CONCLUSIONS: The mycobactericidal activity of sutezolid 600 mg BID or 1200 mg QD was readily detected in sputum and blood. Both schedules were generally safe and well tolerated. Further studies of sutezolid in tuberculosis treatment are warranted. Trial Registration ClinicalTrials.gov NCT0122564

High-accuracy relativistic many-body calculations of van der Waals coefficients C_6 for alkaline-earth atoms

Relativistic many-body calculations of van der Waals coefficients C_6 for dimers correlating to two ground state alkaline-earth atoms at large internuclear separations are reported. The following values and uncertainties were determined : C_6 = 214(3) for Be, 627(12) for Mg, 2221(15) for Ca, 3170(196) for Sr, and 5160(74) for Ba in atomic units.Comment: 5 pages, submitted to Phys. Rev.

The Effect of Metabolic Syndrome on the Occurrence of Restenosis After Carotid Endarterectomy

Objectives: The metabolic syndrome (MetS) is a cluster of risk factors for cardiovascular disease. The effect of MetS on clinical outcome in patients with cerebrovascular disease remains largely unknown because conflicting results have been published. This study aimed to determine the influence of MetS on the occurrence of restenosis after carotid endarterectomy (CEA). Methods: All patients who underwent CEA between June 2003 and December 2014 in two tertiary academic referral centres in The Netherlands were included. MetS was defined if three or more of the following criteria were present: hypertension, obesity, high fasting serum blood glucose, high serum triglycerides, or low serum high density lipoprotein cholesterol. The primary outcome measure was the occurrence of ipsilateral restenosis after index surgery. The secondary outcome measure was (all cause) mortality during follow up. For the primary analysis, missing data were multiply imputed using multivariable imputation by chained equations. A Cox proportional hazards model was used to perform an adjusted analysis on the multiply imputed data sets. Results: A total of 1668 CEA procedures (in 1577 patients) were performed. The presence or absence of MetS could not be determined in 263 patients because of missing data. There was no significant difference in freedom from restenosis in the MetS group vs. the no-MetS group (hazard ratio [HR], 1.10; 95% confidence interval [CI] 0.98-1.23; p = .10) or in all cause mortality (HR 1.20; 95% CI 0.94-1.54; p = .14). Conclusion: This study shows that MetS does not predict restenosis after CEA. Also, the presence of MetS did not influence patient survival negatively

Autism-Like Behavior and Epigenetic Changes Associated with Autism as Consequences of In Utero Exposure to Environmental Pollutants in a Mouse Model

We tested the hypothesis that in utero exposure to heavy metals increases autism-like behavioral phenotypes in adult animals and induces epigenetic changes in genes that have roles in the etiology of autism. Mouse dams were treated with cadmium, lead, arsenate, manganese, and mercury via drinking water from gestational days (E) 1–10. Valproic acid (VPA) injected intraperitoneally once on (E) 8.5 served as a positive control. Young male offspring were tested for behavioral deficits using four standardized behavioral assays. In this study, in utero exposure to heavy metals resulted in multiple behavioral abnormalities that persisted into adulthood. VPA and manganese induced changes in perseverative/impulsive behavior and social dominance behavior, arsenic caused changes only in perseverative/impulsive behavior, and lead induced abnormalities in social interaction in comparison to the control animals. Brain samples from Mn, Pb, and VPA treated and control animals were evaluated for changes in CpG island methylation in promoter regions and associated changes in gene expression. The Chd7 gene, essential for neural crest cell migration and patterning, was found to be hypomethylated in each experimental animal tested compared to water-treated controls. Furthermore, distinct patterns of CpG island methylation yielded novel candidate genes for further investigation

Somatic neurofibromatosis type 1 (NF1) inactivation characterizes NF1-associated pilocytic astrocytoma

Low-grade brain tumors (pilocytic astrocytomas) arising in the neurofibromatosis type 1 (NF1) inherited cancer predisposition syndrome are hypothesized to result from a combination of germline and acquired somatic NF1 tumor suppressor gene mutations. However, genetically engineered mice (GEM) in which mono-allelic germline Nf1 gene loss is coupled with bi-allelic somatic (glial progenitor cell) Nf1 gene inactivation develop brain tumors that do not fully recapitulate the neuropathological features of the human condition. These observations raise the intriguing possibility that, while loss of neurofibromin function is necessary for NF1-associated low-grade astrocytoma development, additional genetic changes may be required for full penetrance of the human brain tumor phenotype. To identify these potential cooperating genetic mutations, we performed whole-genome sequencing (WGS) analysis of three NF1-associated pilocytic astrocytoma (PA) tumors. We found that the mechanism of somatic NF1 loss was different in each tumor (frameshift mutation, loss of heterozygosity, and methylation). In addition, tumor purity analysis revealed that these tumors had a high proportion of stromal cells, such that only 50%–60% of cells in the tumor mass exhibited somatic NF1 loss. Importantly, we identified no additional recurrent pathogenic somatic mutations, supporting a model in which neuroglial progenitor cell NF1 loss is likely sufficient for PA formation in cooperation with a proper stromal environment