147 research outputs found

    Space-time variation of malaria incidence in Yunnan province, China

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    BACKGROUND Understanding spatio-temporal variation in malaria incidence provides a basis for effective disease control planning and monitoring. METHODS Monthly surveillance data between 1991 and 2006 for Plasmodium vivax and Plasmodium falciparum malaria across 128 counties were assembled for Yunnan, a province of China with one of the highest burdens of malaria. County-level Bayesian Poisson regression models of incidence were constructed, with effects for rainfall, maximum temperature and temporal trend. The model also allowed for spatial variation in county-level incidence and temporal trend, and dependence between incidence in June-September and the preceding January-February. RESULTS Models revealed strong associations between malaria incidence and both rainfall and maximum temperature. There was a significant association between incidence in June-September and the preceding January-February. Raw standardised morbidity ratios showed a high incidence in some counties bordering Myanmar, Laos and Vietnam, and counties in the Red River valley. Clusters of counties in south-western and northern Yunnan were identified that had high incidence not explained by climate. The overall trend in incidence decreased, but there was significant variation between counties. CONCLUSION Dependence between incidence in summer and the preceding January-February suggests a role of intrinsic host-pathogen dynamics. Incidence during the summer peak might be predictable based on incidence in January-February, facilitating malaria control planning, scaled months in advance to the magnitude of the summer malaria burden. Heterogeneities in county-level temporal trends suggest that reductions in the burden of malaria have been unevenly distributed throughout the province.This project was supported by a University of Queensland New Research Scientist Start-Up Fund grant. RWS is a Wellcome Trust Principal Research Fellow (#079080) and receives additional support from the Wellcome Trust for the Malaria Atlas Project (MAP, http://www.map.ox.ac.uk)

    Periodontal regeneration risk assessment in the treatment of intrabony defects.

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    BACKGROUND: Regenerative approaches performed in periodontics seems to be efficient in treating intrabony defects. There are, however, many factors that may affect the predictability of the regenerative procedures. The present article aimed to propose a new risk assessment tool for treating periodontal intrabony defects by regenerative therapy. METHODS: Different variables that could affect the success of a regenerative procedure were considered based on their impact on (i) the wound healing potential, promoting wound stability, cells, and angiogenesis, or (ii) the ability to clean the root surface and maintain an optimal plaque control or (iii) aesthetics (risk for gingival recession). RESULTS: The risk assessment variables were divided into a patient, tooth, defect, and operator level. Patient-related factors included medical conditions such as diabetes, smoking habit, plaque control, compliance with supportive care, and expectations. Tooth-related factors included prognosis, traumatic occlusal forces or mobility, endodontic status, root surface topography, soft tissue anatomy, and gingival phenotype. Defect-associated factors included local anatomy (number of residual bone walls, width, and depth), furcation involvement, cleansability, and number of sides of the root involved. Operator-related factors should not be neglected and included the clinician\u27s level of experience, the presence of environmental stress factors, and the use of checklists in the daily routine. CONCLUSIONS: Using a risk assessment comprised of patient-, tooth-, defect- and operator-level factors can aid the clinician in identifying challenging characteristics and in the treatment decision process

    Molecular mechanism of MLL PHD3 and RNA recognition by the Cyp33 RRM domain

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    The nuclear protein cyclophilin 33 (Cyp33) is a peptidyl-prolyl cis-trans isomerase that catalyzes cis-trans isomerization of the peptide bond preceding a proline and promotes folding and conformational changes in folded and unfolded proteins. The N-terminal RNA-recognition motif (RRM) domain of Cyp33 has been found to associate with the third plant homeodomain (PHD3) finger of the mixed lineage leukemia (MLL) proto-oncoprotein and a poly(A) RNA sequence. Here, we report a 1.9 A resolution crystal structure of the RRM domain of Cyp33 and describe the molecular mechanism of PHD3 and RNA recognition. The Cyp33 RRM domain folds into a five-stranded antiparallel beta-sheet and two alpha-helices. The RRM domain, but not the catalytic module of Cyp33, binds strongly to PHD3, exhibiting a 2 muM affinity as measured by isothermal titration calorimetry. NMR chemical shift perturbation (CSP) analysis and dynamics data reveal that the beta strands and the beta2-beta3 loop of the RRM domain are involved in the interaction with PHD3. Mutations in the PHD3-binding site or deletions in the beta2-beta3 loop lead to a significantly reduced affinity or abrogation of the interaction. The RNA-binding pocket of the Cyp33 RRM domain, mapped on the basis of NMR CSP and mutagenesis, partially overlaps with the PHD3-binding site, and RNA association is abolished in the presence of MLL PHD3. Full-length Cyp33 acts as a negative regulator of MLL-induced transcription and reduces the expression levels of MLL target genes MEIS1 and HOXA9. Together, these in vitro and in vivo data provide insight into the multiple functions of Cyp33 RRM and suggest a Cyp33-dependent mechanism for regulating the transcriptional activity of MLL

    The Influence of the BuccoĂą Palatal Distance on Sinus Augmentation Outcomes

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141630/1/jper1041.pd

    Specificity of the STAT4 Genetic Association for Severe Disease Manifestations of Systemic Lupus Erythematosus

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    Systemic lupus erythematosus (SLE) is a genetically complex disease with heterogeneous clinical manifestations. A polymorphism in the STAT4 gene has recently been established as a risk factor for SLE, but the relationship with specific SLE subphenotypes has not been studied. We studied 137 SNPs in the STAT4 region genotyped in 4 independent SLE case series (total n = 1398) and 2560 healthy controls, along with clinical data for the cases. Using conditional testing, we confirmed the most significant STAT4 haplotype for SLE risk. We then studied a SNP marking this haplotype for association with specific SLE subphenotypes, including autoantibody production, nephritis, arthritis, mucocutaneous manifestations, and age at diagnosis. To prevent possible type-I errors from population stratification, we reanalyzed the data using a subset of subjects determined to be most homogeneous based on principal components analysis of genome-wide data. We confirmed that four SNPs in very high LD (r2 = 0.94 to 0.99) were most strongly associated with SLE, and there was no compelling evidence for additional SLE risk loci in the STAT4 region. SNP rs7574865 marking this haplotype had a minor allele frequency (MAF) = 31.1% in SLE cases compared with 22.5% in controls (OR = 1.56, p = 10−16). This SNP was more strongly associated with SLE characterized by double-stranded DNA autoantibodies (MAF = 35.1%, OR = 1.86, p<10−19), nephritis (MAF = 34.3%, OR = 1.80, p<10−11), and age at diagnosis<30 years (MAF = 33.8%, OR = 1.77, p<10−13). An association with severe nephritis was even more striking (MAF = 39.2%, OR = 2.35, p<10−4 in the homogeneous subset of subjects). In contrast, STAT4 was less strongly associated with oral ulcers, a manifestation associated with milder disease. We conclude that this common polymorphism of STAT4 contributes to the phenotypic heterogeneity of SLE, predisposing specifically to more severe disease

    The Gemini Planet Imager Exoplanet Survey: Giant Planet and Brown Dwarf Demographics From 10-100 AU

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    We present a statistical analysis of the first 300 stars observed by the Gemini Planet Imager Exoplanet Survey (GPIES). This subsample includes six detected planets and three brown dwarfs; from these detections and our contrast curves we infer the underlying distributions of substellar companions with respect to their mass, semi-major axis, and host stellar mass. We uncover a strong correlation between planet occurrence rate and host star mass, with stars M >> 1.5 M⊙M_\odot more likely to host planets with masses between 2-13 MJup_{\rm Jup} and semi-major axes of 3-100 au at 99.92% confidence. We fit a double power-law model in planet mass (m) and semi-major axis (a) for planet populations around high-mass stars (M >> 1.5M⊙_\odot) of the form d2Ndmda∝mαaÎČ\frac{d^2 N}{dm da} \propto m^\alpha a^\beta, finding α\alpha = -2.4 ±\pm 0.8 and ÎČ\beta = -2.0 ±\pm 0.5, and an integrated occurrence rate of 9−4+59^{+5}_{-4}% between 5-13 MJup_{\rm Jup} and 10-100 au. A significantly lower occurrence rate is obtained for brown dwarfs around all stars, with 0.8−0.5+0.8^{+0.8}_{-0.5}% of stars hosting a brown dwarf companion between 13-80 MJup_{\rm Jup} and 10-100 au. Brown dwarfs also appear to be distributed differently in mass and semi-major axis compared to giant planets; whereas giant planets follow a bottom-heavy mass distribution and favor smaller semi-major axes, brown dwarfs exhibit just the opposite behaviors. Comparing to studies of short-period giant planets from the RV method, our results are consistent with a peak in occurrence of giant planets between ~1-10 au. We discuss how these trends, including the preference of giant planets for high-mass host stars, point to formation of giant planets by core/pebble accretion, and formation of brown dwarfs by gravitational instability.Comment: 52 pages, 18 figures. AJ in pres

    The Gemini Planet Imager View of the HD 32297 Debris Disk

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    We present new H-band scattered light images of the HD 32297 edge-on debris disk obtained with the Gemini Planet Imager. The disk is detected in total and polarized intensity down to a projected angular separation of 0.?15, or 20 au. On the other hand, the large-scale swept-back halo remains undetected, likely a consequence of its markedly blue color relative to the parent body belt. We analyze the curvature of the disk spine and estimate a radius of ?100 au for the parent body belt, smaller than past scattered light studies but consistent with thermal emission maps of the system. We employ three different flux-preserving post-processing methods to suppress the residual starlight and evaluate the surface brightness and polarization profile along the disk spine. Unlike past studies of the system, our high-fidelity images reveal the disk to be highly symmetric and devoid of morphological and surface brightness perturbations. We find the dust scattering properties of the system to be consistent with those observed in other debris disks, with the exception of HR 4796. Finally, we find no direct evidence for the presence of a planetary-mass object in the system
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