Quantification of arsenic, lead, mercury and cadmium in newborn dried blood spots

AbstractExposures to heavy metals during fetal and perinatal development are of particular concern. Yet, the health impacts of exposures to toxic metals during these early stages of human development are not well understood due to the paucity of in vivo human data. Dried blood spots (DBS), collected by public health departments to screen for inherited metabolic errors and other disorders, are routinely archived and can be used for exposure assessment. Here we report an improved method for quantifying arsenic, lead, mercury and cadmium in newborn DBS to facilitate epidemiologic research on the health effects of early exposures to toxic metals

Enrichment of cysteinyl adducts of human serum albumin

We report a method to enrich cysteinyl adducts of human serum albumin (HSA)2, representing biomarkers of exposure to systemic electrophiles. Because the major site of HSA adduction is the single free sulfhydryl group at Cys34, we used thiol-affinity resins to remove mercaptalbumin (i.e., unadducted HSA) from the cysteinyl adducts. Electrospray ionization mass spectrometry was used to detect mercaptalbumin and HSA-Cys34 modifications before and after enrichment of HSA. Differences in adduct content were detected across samples of freshly-isolated, archived, and commercial HSA. Cysteinylated and glycosylated adducts were present in all samples with abundances decreasing in the order: commercial HSA > archived HSA > fresh HSA. After enrichment of HSA, mercaptalbumin was no longer observed in mass spectra. The ratio of HSA adducts post-/pre-enrichment, quantified via the Bradford assay and gel electrophoresis, was 0.029 mg adducts/mg HSA in fresh HSA and 0.323 mg adducts/mg HSA in archived HSA. The apparent elevation of adduct levels in archived samples could be due to differences in specimen preparation and storage, rather than to differences in circulating HSA adducts. We conclude that thiol-affinity resins can efficiently remove mercaptalbumin from HSA samples prior to characterization and quantitation of protein adducts of reactive systemic electrophiles

A retrospective analysis of survival and prognostic factors after stereotactic radiosurgery for aggressive meningiomas

BACKGROUND: While most meningiomas are benign, aggressive meningiomas are associated with high levels of recurrence and mortality. A single institution’s Gamma Knife radiosurgical experience with atypical and malignant meningiomas is presented, stratified by the most recent WHO classification. METHODS: Thirty-one patients with atypical and 4 patients with malignant meningiomas treated with Gamma Knife radiosurgery between July 2000 and July 2011 were retrospectively reviewed. All patients underwent prior surgical resection. Overall survival was the primary endpoint and rate of disease recurrence in the brain was a secondary endpoint. Patients who had previous radiotherapy or prior surgical resection were included. Kaplan-Meier and Cox proportional hazards models were used to estimate survival and identify factors predictive of recurrence and survival. RESULTS: Post-Gamma Knife recurrence was identified in 11 patients (31.4%) with a median overall survival of 36 months and progression-free survival of 25.8 months. Nine patients (25.7%) had died. Three-year overall survival (OS) and progression-free survival (PFS) rates were 78.0% and 65.0%, respectively. WHO grade II 3-year OS and PFS were 83.4% and 70.1%, while WHO grade III 3-year OS and PFS were 33.3% and 0%. Recurrence rate was significantly higher in patients with a prior history of benign meningioma, nuclear atypia, high mitotic rate, spontaneous necrosis, and WHO grade III diagnosis on univariate analysis; only WHO grade III diagnosis was significant on multivariate analysis. Overall survival was adversely affected in patients with WHO grade III diagnosis, prior history of benign meningioma, prior fractionated radiotherapy, larger tumor volume, and higher isocenter number on univariate analysis; WHO grade III diagnosis and larger treated tumor volume were significant on multivariate analysis. CONCLUSION: Atypical and anaplastic meningiomas remain difficult tumors to treat. WHO grade III diagnosis and treated tumor volume were significantly predictive of recurrence and survival on multivariate analysis in aggressive meningioma patients treated with radiosurgery. Larger tumor size predicts poor survival, while nuclear atypia, necrosis, and increased mitotic rate are risk factors for recurrence. Clinical and pathologic predictors may help identify patients that are at higher risk for recurrence

Indoor Air Pollutants and Health in the United Arab Emirates

Background: Comprehensive global data on the health effects of indoor air pollutants are lacking. There are few large population-based multi–air pollutant health assessments. Further, little is known about indoor air health risks in the Middle East, especially in countries undergoing rapid economic development

Reflections on Seminole Rock: The Past, Present, and Future of Deference to Agency Regulatory Interpretations

Seminole Rock (or Auer) deference has captured the attention of scholars, policymakers, and the judiciary. That is why Notice & Comment, the blog of the Yale Journal on Regulation and the American Bar Association’s Section of Administrative Law & Regulatory Practice, hosted an online symposium from September 12 to September 23, 2016 on the subject. This symposium contains over 20 contributions addressing different aspects of Seminole Rock deference. Topics include: History of Seminole Rock Empirical Examinations of Seminole Rock Understanding Seminole Rock Within Agencies Understanding Seminole Rock as Applied to Tax, Environmental Law, and Criminal Sentencing Why Seminole Rock Matters Should the Supreme Court Overrule Seminole Rock? Would Overruling Seminole Rock Have Unintended Consequences? What Might the Supreme Court Do? What Might Congress Do? The Future of Seminole Roc

Conducting Environmental Health Research in the Arabian Middle East: Lessons Learned and Opportunities

Background: The Arabian Gulf nations are undergoing rapid economic development, leading to major shifts in both the traditional lifestyle and the environment. Although the pace of change is brisk, there is a dearth of environmental health research in this region

Using Mathematical Models In A Unified Approach To Predicting The Next Emerging Infectious Disease

Emerging infectious diseases (EIDs) pose a significant threat to human health, global economies, and conservation (Smolinski et al. 2003). They are defined as diseases that have recently increased in incidence (rate of the development of new cases during a given time period), are caused by pathogens that recently moved from one host population to another, have recently evolved, or have recently exhibited a change in pathogenesis (Morse 1993; Krause 1994). Some EIDs threaten global public health through pandemics with large-scale mortality (e.g., HN/AIDS). Others cause smaller outbreaks but have high case fatality ratios or lack effective therapies or vaccines (e.g. Ebola virus or methicillin-resistant Staphylococcus aureus). As a group, EIDs cause hundreds of thousands of deaths each year, and some outbreaks (e.g., SARS, H5N1) have cost the global economy tens of billions of dollars. Emerging diseases also affect plants, livestock, and wildlife and are recognized as a Significant threat to the conservation of biodiversity (Daszak et al. 2000). Approximately 60% of emerging human disease events are zoonotic, and over 75% of these diseases originate in wildlife (Jones et al. 2008). The global response to such epidemics is frequently reactive, and the effectiveness of conventional disease control operations is often too little, too late\u27: With rising globalization, the ease with which diseases spread globally has increased dramatically in recent times. Also, interactions between humans and wildlife have intensified through trade markets, agricultural intensification, logging and mining, and other forms of development that encroach into wild areas. Rapid human population growth, land use change, and change in global trade and travel require a shift toward a proactive, predictive, and preventive approaches for the next zoonotic pandemic

Adaptive divergence despite strong genetic drift: genomic analysis of the evolutionary mechanisms causing genetic differentiation in the island fox (\u3ci\u3eUrocyon littoralis\u3c/i\u3e)

The evolutionary mechanisms generating the tremendous biodiversity of islands have long fascinated evolutionary biologists. Genetic drift and divergent selection are pre- dicted to be strong on islands and both could drive population divergence and specia- tion. Alternatively, strong genetic drift may preclude adaptation. We conducted a genomic analysis to test the roles of genetic drift and divergent selection in causing genetic differentiation among populations of the island fox (Urocyon littoralis). This species consists of six subspecies, each of which occupies a different California Chan- nel Island. Analysis of 5293 SNP loci generated using Restriction-site Associated DNA (RAD) sequencing found support for genetic drift as the dominant evolutionary mech- anism driving population divergence among island fox populations. In particular, pop- ulations had exceptionally low genetic variation, small Ne (range = 2.1–89.7; median = 19.4), and significant genetic signatures of bottlenecks. Moreover, islands with the lowest genetic variation (and, by inference, the strongest historical genetic drift) were most genetically differentiated from mainland grey foxes, and vice versa, indicating genetic drift drives genome-wide divergence. Nonetheless, outlier tests identified 3.6–6.6% of loci as high FST outliers, suggesting that despite strong genetic drift, divergent selection contributes to population divergence. Patterns of similarity among populations based on high FST outliers mirrored patterns based on morphology, providing additional evidence that outliers reflect adaptive divergence. Extremely low genetic variation and small Ne in some island fox populations, particularly on San Nicolas Island, suggest that they may be vulnerable to fixation of deleterious alleles, decreased fitness and reduced adaptive potential

Measurement of Angular Distributions and R= sigma_L/sigma_T in Diffractive Electroproduction of rho^0 Mesons

Production and decay angular distributions were extracted from measurements of exclusive electroproduction of the rho^0(770) meson over a range in the virtual photon negative four-momentum squared 0.5< Q^2 <4 GeV^2 and the photon-nucleon invariant mass range 3.8< W <6.5 GeV. The experiment was performed with the HERMES spectrometer, using a longitudinally polarized positron beam and a ^3He gas target internal to the HERA e^{+-} storage ring. The event sample combines rho^0 mesons produced incoherently off individual nucleons and coherently off the nucleus as a whole. The distributions in one production angle and two angles describing the rho^0 -> pi+ pi- decay yielded measurements of eight elements of the spin-density matrix, including one that had not been measured before. The results are consistent with the dominance of helicity-conserving amplitudes and natural parity exchange. The improved precision achieved at 47 GeV, reveals evidence for an energy dependence in the ratio R of the longitudinal to transverse cross sections at constant Q^2.Comment: 15 pages, 15 embedded figures, LaTeX for SVJour(epj) document class Revision: Fig. 15 corrected, recent data added to Figs. 10,12,14,15; minor changes to tex

Challenges in quantifying changes in the global water cycle

Human influences have likely already impacted the large-scale water cycle but natural variability and observational uncertainty are substantial. It is essential to maintain and improve observational capabilities to better characterize changes. Understanding observed changes to the global water cycle is key to predicting future climate changes and their impacts. While many datasets document crucial variables such as precipitation, ocean salinity, runoff, and humidity, most are uncertain for determining long-term changes. In situ networks provide long time-series over land but are sparse in many regions, particularly the tropics. Satellite and reanalysis datasets provide global coverage, but their long-term stability is lacking. However, comparisons of changes among related variables can give insights into the robustness of observed changes. For example, ocean salinity, interpreted with an understanding of ocean processes, can help cross-validate precipitation. Observational evidence for human influences on the water cycle is emerging, but uncertainties resulting from internal variability and observational errors are too large to determine whether the observed and simulated changes are consistent. Improvements to the in situ and satellite observing networks that monitor the changing water cycle are required, yet continued data coverage is threatened by funding reductions. Uncertainty both in the role of anthropogenic aerosols, and due to large climate variability presently limits confidence in attribution of observed changes