Tropical Cyclone Diurnal Cycle as Observed by TRMM

Using infrared satellite data, previous work has shown a consistent diurnal cycle in the pattern of cold cloud tops around mature tropical cyclones. In particular, an increase in the coverage by cold cloud tops often occurs in the inner core of the storm around the time of sunset and subsequently propagates outward to several hundred kilometers over the course of the following day. This consistent cycle may have important implications for structure and intensity changes of tropical cyclones and the forecasting of such changes. Because infrared satellite measurements are primarily sensitive to cloud top, the goal of this study is to use passive and active microwave measurements from the Tropical Rainfall Measurement Mission (TRMM) Microwave Imager (TMI) and Precipitation Radar (PR), respectively, to examine and better understand the tropical cyclone diurnal cycle throughout a larger depth of the storm's clouds. The National Hurricane Center's best track dataset was used to extract all PR and TMI pixels within 1000 km of each tropical cyclone that occurred in the Atlantic basin between 1998-2011. Then the data was composited according to radius (100-km bins from 0-1000 km) and local standard time (LST; 3-hr bins). Specifically, PR composites involved finding the percentage of pixels with reflectivity greater than or equal to 20 dBZ at various heights (i.e., 2-14 km in increments of 2 km) as a function of radius and time. The 37- and 85- GHz TMI channels are especially sensitive to scattering by precipitation-sized ice in the mid to upper portions of clouds. Hence, the percentage of 37- and 85-GHz polarization corrected temperatures less than various thresholds were calculated using data from all storms as a function of radius and time. For 37 GHz, thresholds of 260 K, 265 K, 270 K, and 275 K were used, and for 85 GHz, thresholds of 200-270 K in increments of 10 K were utilized. Note that convection forced by the interactions of a tropical cyclone with land (e.g., due to frictional convergence) may disrupt the natural convective cycle of a cyclone. Hence, only data pertaining to storms whose centers were greater than 300 km from land were included in the composites. Early results suggest the presence of a diurnal cycle in the PR composites of all Atlantic basin tropical cyclones from a height of 2-12 km from approximately 0-400 km radius, but the cycle is most apparent above 6 km. At a height of 8 km, there is a peak (minimum) in the percentage of PR pixels greater than or equal to 20 dBZ near 0 (21) LST in the inner core with some indication that this signal propagates outward with time. In contrast, the 37- and 85-GHz composites show little indication of a diurnal cycle at any radii, regardless of the threshold used. Ongoing work with this project will involve sub-setting the composites according to storm intensity to see if the diurnal cycle varies with storm strength. Moderate to strong vertical wind shear often leads to asymmetries in tropical cyclone convection and may disrupt the cyclone's natural diurnal cycle. Therefore, wind shear thresholds will be applied to the composites to determine if the diurnal cycle becomes more apparent in a low shear environment. Finally, other work to be completed will involve developing composites for other tropical cyclone basins, including the East Pacific, Northwest Pacific, South Pacific, and Indian Ocean

Lightning Observations and Tropical Cyclogenesis in the Atlantic and East Pacific

It has been hypothesized that deep, intense convective-scale "hot" towers may aid the process of tropical cyclogenesis and intensification through dynamic and thermodynamic feedbacks on the larger meso-to-synoptic scale circulation. In this study, we make use of NCEP Reanalysis data and Tropical Rainfall Measurement Mission (TRMM) lightning imaging sensor (LIS), precipitation radar (PR), and microwave imager (TMI) data to investigate the role that widespread and/or intense lightning-producing convection (i.e., "electrically-hot towers") present in African easterly waves (AEWs) may play in tropical cyclogenesis over the Atlantic, Caribbean, and East Pacific regions. NCEP Reanalysis 700 hPa meridional winds for the months of June to November for the years 2001-2009 were analyzed for the domain of 5degN-20degN and 130degW-20degE in order to partition individual AEWs into northerly, southerly, trough, and ridge phases. Subsequently, information from National Hurricane Center (NHC) storm reports was used to divide the waves into developing and non-developing waves. In addition, information from the NHC reports was used to further divide the developing waves into those waves that spawned storms that only developed to tropical storm strength and those that spawned storms that reached hurricane strength. The developing waves were also divided by the region in which they developed. To assess the evolution of convection associated with the AEWs as they propagated across our analysis domain, the full 130degW-20degE domain was divided into five longitude bands, and waves were analyzed for each band. To help determine the gross nature of the smaller convective scale, composites were created of all developing and non-developing waves as a function of AEW wave phase over the full analysis domain and each longitude band by compositing TRMM PR, TMI, LIS, and IR brightness temperature data extracted from the NASA global-merged infrared brightness temperature dataset. Finally, similar composites were created using various NCEP variables to assess the nature of the larger scale environment and circulation

Electrically-Active Convection in Tropical Easterly Waves and Implications for Tropical Cyclogenesis in the Atlantic and East Pacific

In this study, we investigate the characteristics of tropical easterly wave convection and the possible implications of convective structure on tropical cyclogenesis and intensification over the Atlantic Ocean and East Pacific using data from the Tropical Rainfall Measurement Mission Microwave Imager, Precipitation Radar (PR), and Lightning Imaging Sensor as well as infrared (IR) brightness temperature data from the NASA global-merged IR brightness temperature dataset. Easterly waves were partitioned into northerly, southerly, trough, and ridge phases based on the 700-hPa meridional wind from the NCEP-NCAR reanalysis dataset. Waves were subsequently divided according to whether they did or did not develop tropical cyclones (i.e., developing and nondeveloping, respectively), and developing waves were further subdivided according to development location. Finally, composites as a function of wave phase and category were created using the various datasets. Results suggest that the convective characteristics that best distinguish developing from nondeveloping waves vary according to where developing waves spawn tropical cyclones. For waves that developed a cyclone in the Atlantic basin, coverage by IR brightness temperatures .240 K and .210 K provide the best distinction between developing and nondeveloping waves. In contrast, several variables provide a significant distinction between nondeveloping waves and waves that develop cyclones over the East Pacific as these waves near their genesis location including IR threshold coverage, lightning flash rates, and low-level (<4.5 km) PR reflectivity. Results of this study may be used to help develop thresholds to better distinguish developing from nondeveloping waves and serve as another aid for tropical cyclogenesis forecasting

Matrix Metalloproteinase (MMP)-8 and MMP-9 in Cerebrospinal Fluid during Bacterial Meningitis: Association with Blood-Brain Barrier Damage and Neurological Sequelae

To evaluate the spectrum and regulation of matrix metalloproteinases (MMPs) in bacterial meningitis (BM), concentrations of MMP-2, MMP-3, MMP-8, and MMP-9 and endogenous inhibitors of metalloproteinases (TIMP-1 and TIMP-2) were measured in the cerebrospinal fluid (CSF) of 27 children with BM. MMP-8 and MMP-9 were detected in 91% and 97%, respectively, of CSF speci-mens from patients but were not detected in control patients. CSF levels of MMP-9 were higher (P <.05) in 5 patients who developed hearing impairment or secondary epilepsy than in those who recovered without neurological deficits. Levels of MMP-9 correlated with concentrations of TIMP-1 (P <.001) and tumor necrosis factor-α (P =.03). Repeated lumbar punctures showed that levels of MMP-8 and MMP-9 were regulated independently and did not correlate with the CSF cell count. Therefore, MMPs may derive not only from granulocytes infiltrating the CSF space but also from parenchymal cells of the meninges and brain. High concentrations of MMP-9 are a risk factor for the development of postmeningitidal neurological sequela

PIB is a non-specific imaging marker of amyloid-beta (Aβ) peptide-related cerebral amyloidosis

The in vivo imaging probe [11C]-PIB (Pittsburgh Compound B, N-methyl[11C]2-(4′-methylaminophenyl-6-hydroxybenzathiazole) is under evaluation as a key imaging tool in Alzheimer's disease (AD) and to date has been assumed to bind with high affinity and specificity to the amyloid structures associated with classical plaques (CPs), one of the pathological hallmarks of the disease. However, no studies have systematically investigated PIB binding to human neuropathological brain specimens at the tracer concentrations achieved during in vivo imaging scans. Using a combination of autoradiography and histochemical techniques, we demonstrate that PIB, in addition to binding CPs clearly delineates diffuse plaques and cerebrovascular amyloid angiopathy (CAA). The interaction of PIB with CAA was not fully displaceable and this may be linked to the apolipoprotein E-ε4 allele. PIB was also found to label neurofibrillary tangles, although the overall intensity of this binding was markedly lower than that associated with the amyloid-beta (Aβ) pathology. The data provide a molecular explanation for PIB's limited specificity in diagnosing and monitoring disease progression in AD and instead indicate that the ligand is primarily a non-specific marker of Aβ-peptide related cerebral amyloidosi

Relation between tropical easterly wave convection and tropical cyclogenesis over the Atlantic and east Pacific

The characteristics of tropical easterly wave convection and the possible implications of convective structure on tropical cyclogenesis and intensification over the Atlantic Ocean and East Pacific were investigated in this study. Easterly waves were partitioned into northerly, southerly, trough, and ridge phases based on 700-hPa meridional wind data. Waves were subsequently divided according to whether they did or did not develop tropical cyclones (i.e., developing waves [DWs] and non-developing waves [NDWs], respectively), and composites of synoptic-scale and convective-scale variables as a function of wave phase and category were created using Eulerian and Lagrangian frameworks. Results of both the Eulerian and Lagrangian composites indicate that the greatest difference between DWs and NDWs is observed for the fractional coverage by infrared brightness temperatures ≤240 K and ≤210 K. Indicators of convective intensity (e.g., lightning flash rates, mean convective reflectivity profiles) provide relatively few statistically significant differences between DWs and NDWs, except over the East Pacific. In addition, the Lagrangian composites suggest that as genesis is approached for DWs, the coverage by convection and cold cloudiness increases, while convective intensity decreases. In contrast, convective coverage and intensity both increase with time for NDWs. Thus, the results of both the Lagrangian and Eulerian frameworks suggest that the coverage by cold cloudiness/convection is generally more important than convective intensity for tropical cyclogenesis. In terms of large-scale variables, both types of composites suggest that enhanced upper-level (~200 hPa) divergence and deep-layer moisture are particularly important for cyclogenesis and for distinguishing DWs from NDWs. The Eulerian composites also suggest that favorable large-scale conditions for cyclogenesis (e.g., significantly greater low-level [~925 hPa] vorticity) occur for Atlantic DWs relative to NDWs over regions farther east away from where these DWs spawn cyclones. In contrast, favorable conditions for tropical cyclogenesis don\u27t develop for waves that spawn tropical cyclones over the East Pacific until these waves move over the East Pacific. Results of this study contribute to a greater understanding of the processes involved in tropical cyclogenesis and may contribute to applications that help improve forecasts of cyclogenesis from easterly waves

Multivariate characterization of white matter heterogeneity in autism spectrum disorder

The complexity and heterogeneity of neuroimaging findings in individuals with autism spectrum disorder has suggested that many of the underlying alterations are subtle and involve many brain regions and networks. The ability to account for multivariate brain features and identify neuroimaging measures that can be used to characterize individual variation have thus become increasingly important for interpreting and understanding the neurobiological mechanisms of autism. In the present study, we utilize the Mahalanobis distance, a multidimensional counterpart of the Euclidean distance, as an informative index to characterize individual brain variation and deviation in autism. Longitudinal diffusion tensor imaging data from 149 participants (92 diagnosed with autism spectrum disorder and 57 typically developing controls) between 3.1 and 36.83 years of age were acquired over a roughly 10-year period and used to construct the Mahalanobis distance from regional measures of white matter microstructure. Mahalanobis distances were significantly greater and more variable in the autistic individuals as compared to control participants, demonstrating increased atypicalities and variation in the group of individuals diagnosed with autism spectrum disorder. Distributions of multivariate measures were also found to provide greater discrimination and more sensitive delineation between autistic and typically developing individuals than conventional univariate measures, while also being significantly associated with observed traits of the autism group. These results help substantiate autism as a truly heterogeneous neurodevelopmental disorder, while also suggesting that collectively considering neuroimaging measures from multiple brain regions provides improved insight into the diversity of brain measures in autism that is not observed when considering the same regions separately. Distinguishing multidimensional brain relationships may thus be informative for identifying neuroimaging-based phenotypes, as well as help elucidate underlying neural mechanisms of brain variation in autism spectrum disorders

Genotype-Phenotype correlations in multiple sclerosis: HLA genes influence disease severity inferred by 1HMR spectroscopy and MRI measures

Genetic susceptibility to multiple sclerosis (MS) is associated with the human leukocyte antigen (HLA) DRB1*1501 allele. Here we show a clear association between DRB1*1501 carrier status and four domains of disease severity in an investigation of genotype-phenotype associations in 505 robust, clinically well characterized MS patients evaluated cross-sectionally: (i) a reduction in the N-acetyl-aspartate (NAA) concentration within normal appearing white matter (NAWM) via 1HMR spectroscopy (P = 0.025), (ii) an increase in the volume of white matter (WM) lesions utilizing conventional anatomical MRI techniques (1,127 mm3; P = 0.031), (iii) a reduction in normalized brain parenchymal volume (nBPV) (P = 0.023), and (iv) impairments in cognitive function as measured by the Paced Auditory Serial Addition Test (PASAT-3) performance (Mean Z Score: DRB1*1501+: 0.110 versus DRB1*1501-: 0.048; P = 0.004). In addition, DRB1*1501+ patients had significantly more women (74% versus 63%; P = 0.009) and a younger mean age at disease onset (32.4 years versus 34.3 years; P = 0.025). Our findings suggest that DRB1*1501 increases disease severity in MS by facilitating the development of more T2-foci, thereby increasing the potential for irreversible axonal compromise and subsequent neuronal degeneration, as suggested by the reduction of NAA concentrations in NAWM, ultimately leading to a decline in brain volume. These structural aberrations may explain the significant differences in cognitive performance observed between DRB1*1501 groups. The overall goal of a deep phenotypic approach to MS is to develop an array of meaningful biomarkers to monitor the course of the disease, predict future disease behaviour, determine when treatment is necessary, and perhaps to more effectively recommend an available therapeutic interventio

Clomiphene, Metformin, or Both for Infertility in the Polycystic Ovary Syndrome

Background The polycystic ovary syndrome is a common cause of infertility. Clomiphene and insulin sensitizers are used alone and in combination to induce ovulation, but it is unknown whether one approach is superior. Methods We randomly assigned 626 infertile women with the polycystic ovary syndrome to receive clomiphene citrate plus placebo, extended-release metformin plus placebo, or a combination of metformin and clomiphene for up to 6 months. Medication was discontinued when pregnancy was confirmed, and subjects were followed until delivery. Results The live-birth rate was 22.5% (47 of 209 subjects) in the clomiphene group, 7.2% (15 of 208) in the metformin group, and 26.8% (56 of 209) in the combinationtherapy group (P\u3c0.001 for metformin vs. both clomiphene and combination therapy; P=0.31 for clomiphene vs. combination therapy). Among pregnancies, the rate of multiple pregnancy was 6.0% in the clomiphene group, 0% in the metformin group, and 3.1% in the combination-therapy group. The rates of first-trimester pregnancy loss did not differ significantly among the groups. However, the conception rate among subjects who ovulated was significantly lower in the metformin group (21.7%) than in either the clomiphene group (39.5%, P=0.002) or the combinationtherapy group (46.0%, P\u3c0.001). With the exception of pregnancy complications, adverse-event rates were similar in all groups, though gastrointestinal side effects were more frequent, and vasomotor and ovulatory symptoms less frequent, in the metformin group than in the clomiphene group. Conclusions Clomiphene is superior to metformin in achieving live birth in infertile women with the polycystic ovary syndrome, although multiple birth is a complication. (ClinicalTrials.gov number, NCT00068861.

A Systematic Mapping Approach of 16q12.2/FTO and BMI in More Than 20,000 African Americans Narrows in on the Underlying Functional Variation: Results from the Population Architecture using Genomics and Epidemiology (PAGE) Study

Genetic variants in intron 1 of the fat mass- and obesity-associated (FTO) gene have been consistently associated with body mass index (BMI) in Europeans. However, follow-up studies in African Americans (AA) have shown no support for some of the most consistently BMI-associated FTO index single nucleotide polymorphisms (SNPs). This is most likely explained by different race-specific linkage disequilibrium (LD) patterns and lower correlation overall in AA, which provides the opportunity to fine-map this region and narrow in on the functional variant. To comprehensively explore the 16q12.2/FTO locus and to search for second independent signals in the broader region, we fine-mapped a 646-kb region, encompassing the large FTO gene and the flanking gene RPGRIP1L by investigating a total of 3,756 variants (1,529 genotyped and 2,227 imputed variants) in 20,488 AAs across five studies. We observed associations between BMI and variants in the known FTO intron 1 locus: the SNP with the most significant p-value, rs56137030 (8.3×10-6) had not been highlighted in previous studies. While rs56137030was correlated at r2>0.5 with 103 SNPs in Europeans (including the GWAS index SNPs), this number was reduced to 28 SNPs in AA. Among rs56137030 and the 28 correlated SNPs, six were located within candidate intronic regulatory elements, including rs1421085, for which we predicted allele-specific binding affinity for the transcription factor CUX1, which has recently been implicated in the regulation of FTO. We did not find strong evidence for a second independent signal in the broader region. In summary, this large fine-mapping study in AA has substantially reduced the number of common alleles that are likely to be functional candidates of the known FTO locus. Importantly our study demonstrated that comprehensive fine-mapping in AA provides a powerful approach to narrow in on the functional candidate(s) underlying the initial GWAS findings in European populations