A case of anaplastic lymphoma kinase-positive renal cell carcinoma coincident with Hodgkin lymphoma.

We report a case of ALK-positive renal cell carcinoma coincident with Hodgkin lymphoma. The patient was a 19 year-old-girl without sickle cell trait. The right renal tumor was discovered concomitantly with Hodgkin lymphoma (HL). After chemotherapy for HL, right nephrectomy was performed. Microscopically, the tumor showed a solid and focally pseudo-papillary growth pattern studded with tubular structures. Most tumor cells were small bland eosinophilic cells, but rhabdoid cells, vacuolated cells, pleomorphic multinucleated giant cells were also admixed. The variety of growth patterns and cell features led us to speculate a possibility of ALK-positive renal cell carcinoma (ALK + RCC). ALK was immunohistochemically positive, and fluorescence in situ hybridization analysis detected a split signal of the ALK gene. We examined previously reported partner genes (STRN, TPM3, VCL and EML4) by RT-PCR, but fusion gene was not detected. RCC showing solid or cribriform growth patterns with vacuolated cells with intracytoplamic lumina, rhabdoid cells, and mucus production indicates the possibility of ALK + RCC.

Particulate matter exposure, prenatal and postnatal windows of susceptibility, and autism spectrum disorders.

BACKGROUND: Recent studies suggest that exposure to traffic-related air pollutants, including particulate matter (PM), is associated with autism spectrum disorder (autism). METHODS: Children with autism were identified by records-based surveillance (n = 645 born in North Carolina in 1994, 1996, 1998, or 2000, and n = 334 born in the San Francisco Bay Area in California in 1996). They were compared with randomly sampled children born in the same counties and years identified from birth records (n = 12,434 in North Carolina and n = 2,232 in California). Exposure to PM less than 10 µm (PM10) at the birth address was assigned to each child by a geostatistical interpolation method using daily concentrations from air pollution regulatory monitors. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for a 10 µg/m increase in PM10 within 3-month periods from preconception through the child's first birthday, adjusting for year, state, maternal education and age, race/ethnicity, and neighborhood-level urbanization and median household income, and including a nonparametric term for week of birth to account for seasonal trends. RESULTS: Temporal patterns in PM10 were pronounced, leading to an inverse correlation between the first- and third-trimester concentrations (r = -0.7). Adjusted ORs were, for the first trimester, 0.86 (95% CI = 0.74-0.99), second trimester, 0.97 (0.83-1.15), and third trimester, 1.36 (1.13-1.63); and, after simultaneously including first- and third-trimester concentrations to account for the inverse correlation, were: first trimester, 1.01 (0.81-1.27) and third trimester, 1.38 (1.03-1.84). CONCLUSIONS: Our study adds to previous work in California showing a relation between traffic-related air pollution and autism, and adds similar findings in an eastern US state, with results consistent with increased susceptibility in the third-trimester.

Large scale air pollution estimation method combining land use regression and chemical transport modeling in a geostatistical framework.

In recognition that intraurban exposure gradients may be as large as between-city variations, recent air pollution epidemiologic studies have become increasingly interested in capturing within-city exposure gradients. In addition, because of the rapidly accumulating health data, recent studies also need to handle large study populations distributed over large geographic domains. Even though several modeling approaches have been introduced, a consistent modeling framework capturing within-city exposure variability and applicable to large geographic domains is still missing. To address these needs, we proposed a modeling framework based on the Bayesian Maximum Entropy method that integrates monitoring data and outputs from existing air quality models based on Land Use Regression (LUR) and Chemical Transport Models (CTM). The framework was applied to estimate the yearly average NO2 concentrations over the region of Catalunya in Spain. By jointly accounting for the global scale variability in the concentration from the output of CTM and the intraurban scale variability through LUR model output, the proposed framework outperformed more conventional approaches.

Myostatin inhibits proliferation of human urethral rhabdosphincter satellite cells.

OBJECTIVES: Myostatin, a member of the transforming growth factor-ß superfamily, is a negative regulator of myogenesis in skeletal muscle. We examined the effect of myostatin and myostatin inhibition by an antagonistic agent, follistatin, on growth of human urethral rhabdosphincter satellite cells (muscle stem cells) to develop a new strategy for treatment of stress urinary incontinence. METHODS: Rhabdosphincter satellite cells were cultured and selected by magnetic affinity cell sorting using an anti-neural cell adhesion molecule antibody. The cells were transfected with simian virus-40 antigen to extend their lifespan. A cell proliferation assay, a cell cycle analysis and an investigation of signal transduction were carried out. The autocrine action of endogenous myostatin by western blotting, real-time reverse transcription polymerase chain reaction and immunoneutralization using an anti-myostatin antibody was also evaluated. RESULTS: Selectively cultured cells expressed markers of striated muscles and successfully differentiated into myotubes. Myostatin inhibited proliferation of these cells through Smad2 phosphorylation and cell cycle arrest. Inhibitory effects of myostatin were reversed by addition of follistatin. However, rhabdosphincter satellite cells did not appear to use autocrine secretion of myostatin to regulate their proliferation. CONCLUSIONS: Inhibition of myostatin function might be a useful pathway in the development of novel strategies for stimulating rhabdosphincter cells regeneration to treat stress urinary incontinence.

Progression of a large syphilis outbreak in rural North Carolina through space and time: Application of a Bayesian Maximum Entropy graphical user interface.

In 2001, the primary and secondary syphilis incidence rate in rural Columbus County, North Carolina was the highest in the nation. To understand the development of syphilis outbreaks in rural areas, we developed and used the Bayesian Maximum Entropy Graphical User Interface (BMEGUI) to map syphilis incidence rates from 1999-2004 in seven adjacent counties in North Carolina. Using BMEGUI, incidence rate maps were constructed for two aggregation scales (ZIP code and census tract) with two approaches (Poisson and simple kriging). The BME maps revealed the outbreak was initially localized in Robeson County and possibly connected to more urban endemic cases in adjacent Cumberland County. The outbreak spread to rural Columbus County in a leapfrog pattern with the subsequent development of a visible low incidence spatial corridor linking Roberson County with the rural areas of Columbus County. Though the data are from the early 2000s, they remain pertinent, as the combination of spatial data with the extensive sexual network analyses, particularly in rural areas gives thorough insights which have not been replicated in the past two decades. These observations support an important role for the connection of micropolitan areas with neighboring rural areas in the spread of syphilis. Public health interventions focusing on urban and micropolitan areas may effectively limit syphilis indirectly in nearby rural areas.

Integrating address geocoding, land use regression, and spatiotemporal geostatistical estimation for groundwater tetrachloroethylene.

Geographic information systems (GIS) based techniques are cost-effective and efficient methods used by state agencies and epidemiology researchers for estimating concentration and exposure. However, budget limitations have made statewide assessments of contamination difficult, especially in groundwater media. Many studies have implemented address geocoding, land use regression, and geostatistics independently, but this is the first to examine the benefits of integrating these GIS techniques to address the need of statewide exposure assessments. A novel framework for concentration exposure is introduced that integrates address geocoding, land use regression (LUR), below detect data modeling, and Bayesian Maximum Entropy (BME). A LUR model was developed for tetrachloroethylene that accounts for point sources and flow direction. We then integrate the LUR model into the BME method as a mean trend while also modeling below detects data as a truncated Gaussian probability distribution function. We increase available PCE data 4.7 times from previously available databases through multistage geocoding. The LUR model shows significant influence of dry cleaners at short ranges. The integration of the LUR model as mean trend in BME results in a 7.5% decrease in cross validation mean square error compared to BME with a constant mean trend.

Long-term cryopreservation of pyramidalis muscle specimens as a source of striated muscle stem cells for treatment of post-prostatectomy stress urinary incontinence.

BACKGROUND: Stem-cell injection into the degenerated external urethral sphincter is a new treatment modality for stress urinary incontinence (SUI). We examined the possibility of long-term cryopreserved pyramidalis muscle (PM) specimens as a source of striated muscle stem cells for the treatment of post-prostatectomy SUI. METHODS: PM specimens were obtained from five male patients (mean age, 61-70 years) who underwent radical prostatectomy for prostate cancer. Specimens (volume, approximately 125 mm³ ) were obtained from the incisional edge, minced, and stored at -80°C in a freezing medium (Cell Banker 1®). After 24-60 months, the specimens were thawed and directly incubated at 37°C. Satellite cells were selectively cultured by magnetic affinity cell sorting using an anti-neural cell adhesion molecule (NCAM) antibody. Osteogenic and adipogenic differentiation were induced by bone morphogenic protein-7 (BMP-7) and γ-linolenic acid, respectively. RESULTS: NCAM-positive cells (>99% purity) were selectively cultured from all cryopreserved PM specimens and confirmed as being of striated muscle origin by the expression of desmin and MyoD. They fused and differentiated into multinucleated myotubes 7 days after incubation in a differentiation induction medium. Stimulation by BMP-7 and γ-linolenic acid induced expression of alkaline phosphatase (osteoblast marker) and lipid deposition within the cytoplasm (adipocyte characteristic), respectively. CONCLUSIONS: Long-term cryopreserved PM specimens can be used to culture muscle stem cells. Therefore, this method may be utilized for SUI treatment when necessary. Moreover, complete remove of the prostate gland without fear of injury to the urethral sphincter may be possible in patients with apical cancer or T3 prostate cancer.

Fecal contamination of shallow tubewells in Bangladesh inversely related to arsenic.

The health risks of As exposure due to the installation of millions of shallow tubewells in the Bengal Basin are known, but fecal contamination of shallow aquifers has not systematically been examined. This could be a source of concern in densely populated areas with poor sanitation because the hydraulic travel time from surface water bodies to shallow wells that are low in As was previously shown to be considerably shorter than for shallow wells that are high in As. In this study, 125 tubewells 6-36 m deep were sampled in duplicate for 18 months to quantify the presence of the fecal indicator Escherichia coli. On any given month, E. coli was detected at levels exceeding 1 most probable number per 100 mL in 19-64% of all shallow tubewells, with a higher proportion typically following periods of heavy rainfall. The frequency of E. coli detection averaged over a year was found to increase with population surrounding a well and decrease with the As content of a well, most likely because of downward transport of E. coli associated with local recharge. The health implications of higher fecal contamination of shallow tubewells, to which millions of households in Bangladesh have switched in order to reduce their exposure to As, need to be evaluated.

Impact of tubewell access and tubewell depth on childhood diarrhea in Matlab, Bangladesh.

BACKGROUND: During the past three decades in Bangladesh, millions of tubewells have been installed to reduce the prevalence of diarrheal disease. This study evaluates the impacts of tubewell access and tubewell depth on childhood diarrhea in rural Bangladesh. METHODS: A total of 59,796 cases of diarrhea in children under 5 were recorded in 142 villages of Matlab, Bangladesh during monthly community health surveys between 2000 and 2006. The location and depth of 12,018 tubewells were surveyed in 2002-04 and integrated with diarrhea and other data in a geographic information system. A proxy for tubewell access was developed by calculating the local density of tubewells around households. Logistic regression models were built to examine the relationship between childhood diarrhea, tubewell density and tubewell depth. Wealth, adult female education, flood control, population density and the child's age were considered as potential confounders. RESULTS: Baris (patrilineally-related clusters of households) with greater tubewell density were associated with significantly less diarrhea (OR (odds ratio) = 0.87, 95% confidence interval (CI): 0.85-0.89). Tubewell density had a greater influence on childhood diarrhea in areas that were not protected from flooding. Baris using intermediate depth tubewells (140-300 feet) were associated with more childhood diarrhea (OR = 1.24, 95% CI: 1.19-1.29) than those using shallow wells (10-140 feet). Baris using deep wells (300-990 feet) had less diarrheal disease than those using shallow wells, however, the difference was significant only when population density was low (< 1000 person/km(2)) or children were at the age of 13-24 months. CONCLUSIONS: Increased access to tubewells is associated with a lower risk of childhood diarrhea. Intermediate- depth wells are associated with more childhood diarrhea compared to shallower or deeper wells. These findings may have implications for on-going efforts to reduce exposure to elevated levels of arsenic contained in groundwater that is pumped in this study area primarily from shallow tubewells.

Construction of highly oriented crystalline surface coordination polymers composed of copper dithiooxamide complexes.

Layer-by-layer bottom-up crystal engineering of metal-organic crystals at the surface of sapphire or glass from organic (rubeanic acid and derivatives) and inorganic (Cu(2+)) components which when mixed in solution form instantly an amorphous solid with high proton conduction.

Spatiotemporal nonattainment assessment of surface water tetrachloroethylene in New Jersey.

Tetrachloroethylene (PCE) is one of the most frequently detected volatile organic compounds (VOCs) in water systems across the USA. In New Jersey, the Department of Environmental Protection (NJDEP) monitors surface water quality at several sites throughout the state. However due to budget and scientific limitations, the sampling data is insufficient to assess all river streams in New Jersey. To address this problem, the objective of this study is to utilize a framework for the space/time estimation of PCE throughout all river reaches in New Jersey over the 1999 through 2003 time period and to track how this concentration evolves over time. We use the Bayesian maximum entropy (BME) mapping method to take into account the composite spatiotemporal variability of PCE, and we produce maps providing a stochastic description of the distribution of PCE at all times throughout the river network. In addition, we conduct a nonattainment assessment analysis by applying a criterion based on the estimated probability distribution function that allows us to identify the river miles that are highly likely in nonattainment of the standard, those that are highly likely in attainment of the standard, and the remaining labeled as nonassessed. Using this criterion we investigate how the river miles contaminated by PCE vary over space and time, and we identify watershed management areas (WMAs) with contamination problems. Finally, a cross validation comparison with a purely spatial analysis demonstrates that the space/time framework leads to a better estimation and a reduction of the number of nonassessed miles.

A Voxel-Based Morphometry Study Reveals Local Brain Structural Alterations Associated with Ambient Fine Particles in Older Women.

Objective: Exposure to ambient fine particulate matter (PM2.5: PM with aerodynamic diameters < 2.5 µm) has been linked with cognitive deficits in older adults. Using fine-grained voxel-wise analyses, we examined whether PM2.5 exposure also affects brain structure. Methods: Brain MRI data were obtained from 1365 women (aged 71-89) in the Women's Health Initiative Memory Study and local brain volumes were estimated using RAVENS (regional analysis of volumes in normalized space). Based on geocoded residential locations and air monitoring data from the U.S. Environmental Protection Agency, we employed a spatiotemporal model to estimate long-term (3-year average) exposure to ambient PM2.5 preceding MRI scans. Voxel-wise linear regression models were fit separately to gray matter (GM) and white matter (WM) maps to analyze associations between brain structure and PM2.5 exposure, with adjustment for potential confounders. Results: Increased PM2.5 exposure was associated with smaller volumes in both cortical GM and subcortical WM areas. For GM, associations were clustered in the bilateral superior, middle, and medial frontal gyri. For WM, the largest clusters were in the frontal lobe, with smaller clusters in the temporal, parietal, and occipital lobes. No statistically significant associations were observed between PM2.5 exposure and hippocampal volumes. Conclusions: Long-term PM2.5 exposures may accelerate loss of both GM and WM in older women. While our previous work linked smaller WM volumes to PM2.5, this is the first neuroimaging study reporting associations between air pollution exposure and smaller volumes of cortical GM. Our data support the hypothesized synaptic neurotoxicity of airborne particles.

Toward step-by-step nuclear growth of surface two-dimensional porphyrin nanonetworks.

We report the development of a solution-based step-by-step technique, which utilizes the coordination bond between metalloporphyrin molecular units and metal linkages and results in the nuclear growth of nano-networks on solid substrates. The growth of the surface structures is strongly influenced by the choice of substrate materials and solvents: the molecule-substrate interaction and the solubility of the molecular units are important parameters in tuning the size and growth of the domains.

A method for estimating urban background concentrations in support of hybrid air pollution modeling for environmental health studies.

Exposure studies rely on detailed characterization of air quality, either from sparsely located routine ambient monitors or from central monitoring sites that may lack spatial representativeness. Alternatively, some studies use models of various complexities to characterize local-scale air quality, but often with poor representation of background concentrations. A hybrid approach that addresses this drawback combines a regional-scale model to provide background concentrations and a local-scale model to assess impacts of local sources. However, this approach may double-count sources in the study regions. To address these limitations, we carefully define the background concentration as the concentration that would be measured if local sources were not present, and to estimate these background concentrations we developed a novel technique that combines space-time ordinary kriging (STOK) of observations with outputs from a detailed chemistry-transport model with local sources zeroed out. We applied this technique to support an exposure study in Detroit, Michigan, for several pollutants (including NOx and PM2.5), and evaluated the estimated hybrid concentrations (calculated by combining the background estimates that addresses this issue of double counting with local-scale dispersion model estimates) using observations. Our results demonstrate the strength of this approach specifically by eliminating the problem of double-counting reported in previous hybrid modeling approaches leading to improved estimates of background concentrations, and further highlight the relative importance of NOx vs. PM2.5 in their relative contributions to total concentrations. While a key limitation of this approach is the requirement for another detailed model simulation to avoid double-counting, STOK improves the overall characterization of background concentrations at very fine spatial scales.

The moving-window Bayesian maximum entropy framework: estimation of PM(2.5) yearly average concentration across the contiguous United States.

Geostatistical methods are widely used in estimating long-term exposures for epidemiological studies on air pollution, despite their limited capabilities to handle spatial non-stationarity over large geographic domains and the uncertainty associated with missing monitoring data. We developed a moving-window (MW) Bayesian maximum entropy (BME) method and applied this framework to estimate fine particulate matter (PM(2.5)) yearly average concentrations over the contiguous US. The MW approach accounts for the spatial non-stationarity, while the BME method rigorously processes the uncertainty associated with data missingness in the air-monitoring system. In the cross-validation analyses conducted on a set of randomly selected complete PM(2.5) data in 2003 and on simulated data with different degrees of missing data, we demonstrate that the MW approach alone leads to at least 17.8% reduction in mean square error (MSE) in estimating the yearly PM(2.5). Moreover, the MWBME method further reduces the MSE by 8.4-43.7%, with the proportion of incomplete data increased from 18.3% to 82.0%. The MWBME approach leads to significant reductions in estimation error and thus is recommended for epidemiological studies investigating the effect of long-term exposure to PM(2.5) across large geographical domains with expected spatial non-stationarity.

Efficacy of hollow-fiber ultrafiltration for microbial sampling in groundwater.

The goal of this study was to test hollow-fiber ultrafiltration as a method for concentrating in situ bacteria and viruses in groundwater samples. Water samples from nine wells tapping a shallow sandy aquifer in a densely populated village in Bangladesh were reduced in volume approximately 400-fold using ultrafiltration. Culture-based assays for total coliforms and Escherichia coli, as well as molecular-based assays for E. coli, Bacteroides, and adenovirus, were used as microbial markers before and after ultrafiltration to evaluate performance. Ultrafiltration increased the concentration of the microbial markers in 99% of cases. However, concentration factors (CF = post-filtration concentration/pre-filtration concentration) for each marker calculated from geometric means ranged from 52 to 1018 compared to the expected value of 400. The efficiency was difficult to quantify because concentrations of some of the markers, especially E. coli and total coliforms, in the well water (WW) collected before ultrafiltration varied by several orders of magnitude during the period of sampling. The potential influence of colloidal iron oxide precipitates in the groundwater was tested by adding EDTA to the pre-filtration water in half of the samples to prevent the formation of precipitates. The use of EDTA had no significant effect on the measurement of culturable or molecular markers across the 0.5 to 10 mg/L range of dissolved Fe(2+) concentrations observed in the groundwater, indicating that colloidal iron did not hinder or enhance recovery or detection of the microbial markers. Ultrafiltration appears to be effective for concentrating microorganisms in environmental water samples, but additional research is needed to quantify losses during filtration.

Lower incidence of inguinal hernia: minilaparotomy radical retropubic prostatectomy compared with conventional technique. A preliminary report.

INTRODUCTION: The purpose of the present study was to compare the incidence of inguinal hernias after conventional and minilaparotomy (minilap) radical retropubic prostatectomy (RRP). PATIENTS AND METHODS: In this retrospective study, we review our experience with 70 consecutive patients with prostate cancer who underwent prostatectomy from April 1995 through March 2001. Of these, 35 patients had conventional RRP, and 35 patients had minilap RRP. RESULTS: Conventional RRP and minilap RRP groups were similar in body mass index (mean 24.4 and 23.5), operative time (mean 260 and 241 min), previous lower abdominal operation record (mean 37.1 and 25.7%), and post-prostatectomy anastomotic strictures (mean 11.4 and 14.3%). The volume of the estimated blood loss was significantly less for minilap RRP (mean 1,220 ml) than for conventional RRP (mean 1,666 ml; p = 0.0194). The incidence of postoperative inguinal hernias was 17.1% (6 of 35), 2.9% (1 of 35), and 3.2% (1 of 31) in conventional RRP, minilap RRP, and unoperated groups, respectively. The incidence of inguinal hernias after minilap RRP was significantly lower than after conventional RRP (p = 0.0464). Seven patients with postoperative inguinal hernias had a high incidence of postoperative strictures (42.9%), while 63 patients without hernia had a low incidence (9.5%). There was a significant difference in developing postoperative strictures between patients with hernia and those without (p = 0.0124). While postoperative stricture and operative technique were different in the hernia and hernia-free groups on univariate analysis, multivariate logistic analysis revealed that the operative technique was an independent factor for the occurrence of inguinal hernias (p = 0.0419). CONCLUSION: Minilap RRP compares favorably with conventional RRP in view of the postoperative inguinal hernia development.