The potential of major ion chemistry to assess groundwater vulnerability of a regional aquifer in southern Quebec (Canada)

Groundwater vulnerability mapping provides useful but limited information for developing protection plans of the resource. Classical vulnerability ranking methods often do not take into account complex hydrostratigraphy and never consider groundwater flow dynamics. The objective of this work was to test the potential of major ion chemistry to assess regional-scale intrinsic groundwater vulnerability. Because it reflects water–sediment and water–rock interactions, the new vulnerability index reflects both infiltration processes and groundwater hydrodynamics. The method was applied on a regional fractured bedrock aquifer located in the Becancour region of southern Quebec (Canada). In this region, hydrogeochemistry shows that freshly recharged groundwater evolves from (Ca, Mg)–HCO3 and Ca–SO4 to Na–HCO3 type with gradually increasing confinement conditions in the fractured aquifer and tends to Na–Cl type locally by mixing with trapped marine pore-water. The new method identified recharge areas as those of the highest vulnerability and gradually decreasing vulnerability as confinement of the aquifer increased. It also highlights local discontinuities in confinement that differ from the regional pattern. Results showed a good correlation between groundwater vulnerability estimated with the new method and nitrate occurrence in groundwater. Eighty-two per cent of all samples presenting detectable nitrate concentrations were characterized by a Hydrogeochemical Vulnerability Index greater than 9 (maximum is 10). The ability of the new vulnerability method to identify areas vulnerable to detectable nitrate concentrations was much higher than that deriving from the DRASTIC method. This work confirms that major ions chemistry contains significant information about groundwater vulnerability and could be used to improve groundwater resource management

Occult Cushing\u27s Syndrome Presenting with Osteoporosis

Osteoporosis is a frequent complication both of endogenous hypercortisolism and of long-term treatment with corticosteroids, but only rarely is it the major clinical feature with the more characteristic features absent or minimally present. In the two patients presented, hypercortisolism was uncovered only during routine evaluation of osteoporosis. This presentation is probably due to slow progression of the disease and is often associated with so-called black adenoma of the adrenal gland. Secondary causes should be sought in all patients with seemingly senile or postmenopausal osteoporosis

Power, sample size and sampling costs for clustered data

The data collected in epidemiological or clinical studies are frequently clustered. In such settings, appropriate variance adjustments must be made in order to estimate the sufficient sample size correctly. This paper works through the sample size calculations for clustered data. Importantly, our explicit variance expressions also enable us to optimize the design with respect to the number of clusters and number of subjects; the objective could be either to maximize the power or to minimize the costs with given costs on the clusters and on the individuals. In our approach, units on different levels and treatment groups can have different costs, but the members of the same cluster are assumed to belong to the same treatment group. Design considerations in the health coaching project TERVA are used as motivating examples. R-functions for carrying out the computations presented are provided. (C) 2011 Elsevier B.V. All rights reserved

Precise U-Pb zircon ages and geochemistry of Jurassic granites, Ellsworth-Whitmore terrane, central Antarctica

The Ellsworth-Whitmore Mountain terrane of central Antarctica was part of the early Paleozoic amalgamation of Gondwana, including a 13,000 m section of Cambrian–Permian sediments in the Ellsworth Mountains deposited on Grenville-age crust. The Jurassic breakup of Gondwana involved a regional, bimodal magmatic event during which the Ellsworth-Whitmore terrane was intruded by intraplate granites before translation of the terrane to its present location in central Antarctica. Five widely separated granitic plutons in the Ellsworth-Whitmore terrane were analyzed for their whole-rock geochemistry (X-ray fluorescence), Sr, Nd, and Pb isotopic compositions, and U-Pb zircon ages to investigate the origins of the terrane magmas and their relationships to mafic magmatism of the 183 Ma Karoo-Ferrar large igneous province (LIP). We report high-precision (±0.1 m.y.) isotope dilution–thermal ionization mass spectrometry (ID-TIMS) U-Pb zircon ages from granitic rocks from the Whitmore Mountains (208.0 Ma), Nash Hills (177.4–177.3 Ma), Linck Nunatak (175.3 Ma), Pagano Nunatak (174.8 Ma), and the Pirrit Hills (174.3–173.9 Ma), and U-Pb sensitive high-resolution ion microprobe (SHRIMP) ages from the Whitmore Mountains (200 ± 5 Ma), Linck Nunatak (180 ± 4 Ma), Pagano Nunatak (174 ± 4 Ma), and the Pirrit Hills (168 ± 4 Ma). We then compared these results with existing K-Ar ages and Nd model ages, and used initial Sr, Nd, and Pb isotope ratios, combined with xenocrystic zircon U-Pb inheritance, to infer characteristics of the source(s) of the parent magmas. We conclude that the Jurassic plutons were not derived exclusively from crustal melts, but rather they are hybridized magmas composed of convecting mantle, subcontinental lithospheric mantle, and lower continental crustal contributions. The mantle contributions to the granites share isotopic similarities to the sources of other Jurassic LIP mafic magmas, including radiogenic 87Sr/86Sr (0.706–0.708), unradiogenic 143Nd/144Nd (εNd < –5), and Pb isotopes consistent with a low-µ source (where μ = 238U/204Pb). Isotopes and zircon xenocrysts point toward a crustal end member of predominantly Proterozoic provenance (0.5–1.0 Ga; Grenville crust), extending the trends illustrated by Ferrar mafic intrusive rocks, but contrasting with the inferred Archean crustal and/or lithospheric mantle contributions to some basalts of the Karoo sector of the LIP. The Ellsworth-Whitmore terrane granites are the result of mafic rocks underplating the hydrous crust, causing crustal melting, hybridization, and fractionation to produce granitic magmas that were eventually emplaced as post-Ferrar, within-plate melts at higher crustal levels as the Ellsworth-Whitmore terrane rifted off Gondwana (47°S) before migrating to its current position (82°S) in central Antarctica

Travel Characteristics and Yellow Fever Vaccine Usage Among US Global TravEpiNet Travelers Visiting Countries with Risk of Yellow Fever Virus Transmission, 2009–2011

Yellow fever (YF) vaccine-associated serious adverse events and changing YF epidemiology have challenged healthcare providers to vaccinate only travelers whose risk of YF during travel is greater than their risk of adverse events. We describe the travel characteristics and YF vaccine use among US travelers visiting Global TravEpiNet clinics from January of 2009 to March of 2011. Of 16,660 travelers, 5,588 (34%) had itineraries to areas with risk of YF virus transmission. Of those travelers visiting one country with YF risk (N = 4,517), 71% were vaccinated at the visit, and 20% were presumed to be immune from prior vaccination. However, travelers visiting friends and relatives (odds ratio [OR] = 2.57, 95% confidence interval [95% CI] = 1.27–5.22) or going to Nigeria (OR = 3.01, 95% CI = 1.37–6.62) were significantly more likely to decline vaccination. To optimize YF vaccine use, clinicians should discuss an individual's risk–benefit assessment of vaccination and close knowledge gaps regarding vaccine use among at-risk populations

Reducing DNA Polymerase in the Absence of Drosophila ATR Leads to P53-Dependent Apoptosis and Developmental Defects

The ability to respond to DNA damage and incomplete replication ensures proper duplication and stability of the genome. Two checkpoint kinases, ATM and ATR, are required for DNA damage and replication checkpoint responses. In Drosophila, the ATR ortholog (MEI-41) is essential for preventing entry into mitosis in the presence of DNA damage. In the absence of MEI-41, heterozygosity for the E(mus304) mutation causes rough eyes. We found that E(mus304) is a mutation in DNApol-α180, which encodes the catalytic subunit of DNA polymerase α. We did not find any defects resulting from reducing Polα by itself. However, reducing Polα in the absence of MEI-41 resulted in elevated P53-dependent apoptosis, rough eyes, and increased genomic instability. Reducing Polα in mutants that lack downstream components of the DNA damage checkpoint (DmChk1 and DmChk2) results in the same defects. Furthermore, reducing levels of mitotic cyclins rescues both phenotypes. We suggest that reducing Polα slows replication, imposing an essential requirement for the MEI-41-dependent checkpoint for maintenance of genome stability, cell survival, and proper development. This work demonstrates a critical contribution of the checkpoint function of MEI-41 in responding to endogenous damage

Use of Japanese Encephalitis Vaccine in US Travel Medicine Practices in Global TravEpiNet

Few data regarding the use of Japanese encephalitis (JE) vaccine in clinical practice are available. We identified 711 travelers at higher risk and 7,578 travelers at lower risk for JE who were seen at US Global TravEpiNet sites from September of 2009 to August of 2012. Higher-risk travelers were younger than lower-risk travelers (median age = 29 years versus 40 years, P < 0.001). Over 70% of higher-risk travelers neither received JE vaccine during the clinic visit nor had been previously vaccinated. In the majority of these instances, clinicians determined that the JE vaccine was not indicated for the higher-risk traveler, which contradicts current recommendations of the Advisory Committee on Immunization Practices. Better understanding is needed of the clinical decision-making regarding JE vaccine in US travel medicine practices

Lead immobilization in thermally remediated soils and igneous rocks

This is the final report for a three-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The principal goal of this project was to investigate the speciation of lead in the environment at LANL and to determine the feasibility of using thermal remediation methods to immobilize lead in the environment. Lead occurs as pyromorphite [Pb(PO{sub 4}){sub 3}(Cl, OH)], cerussite (PbCO{sub 3}) and galena (PbS) in vapor-phase-altered Bandelier Tuff samples. LANL soils primarily contain cerussite and PbO. Thermal remediation experiments at high temperatures (up to 400 C) suggest that thermal immobilization of highly-reactive Pb compounds in the environment may be feasible, but that this technique is not optimal for more refractory lead phases such as cerussite and PbO

Loss of p53 in quaking viable mice leads to Purkinje cell defects and reduced survival

The qkv mutation is a one megabase deletion resulting in abnormal expression of the qkI gene. qkv mice exhibit hypomyelination of the central nervous system and display rapid tremors and seizures as adults. The qkI locus on 6q26-27 has also been implicated as a candidate tumor suppressor gene as the qkI locus maps to a region of genetic instability in Glioblastoma Multiforme (GBM), an aggressive brain tumor of astrocytic lineage. As GBM frequently harbors mutations affecting p53, we crossbred qkv and p53 mutant mice to examine whether qkv mice on a p53−/− background have an increased incidence of GBM. qkv/v; p53−/− mice had a reduced survival rate compared to p53−/− littermates, and the cause of death of the majority of the mice remains unknown. In addition, immunohistochemistry revealed Purkinje cell degeneration in the cerebellum. These results suggest that p53 and qkI are genetically linked for neuronal maintenance and survival

Amino Alkynylisoquinoline and Alkynylnaphthyridine Compounds Potently Inhibit Acute Myeloid Leukemia Proliferation in Mice

B ackground: Acute myeloid leukemia (AML) remains one of the most lethal, rarely cured cancers, despite decades of active development of AML therapeutics. Currently, the 5-year survival of AML patients is about 30% and for elderly patients, the rate drops to b10%. About 30% of AML patients harbor an activating mutation in the tyrosine kinase domain (TKD) of Fms-Like Tyrosine kinase 3 (FLT3) or a FLT3 internal tandem duplication (FLT3-ITD). In- hibitors of FLT3, such as Rydapt that was recently approved by the FDA, have shown good initial response but pa- tients often relapse due to secondary mutations in the FLT3 TKD, like D835Y and F691 L mutations. Methods: Alkynyl aminoisoquinoline and naphthyridine compounds were synthesized via Sonogashira coupling. The compounds were evaluated for their in vitro and in vivo effects on leukemia growth. Findings: The compounds inhibited FLT3 kinase activity at low nanomolar concentrations. The lead compound, HSN431, also inhibited Src kinase activity. The compounds potently inhibited the viability of MV4–11 and MOLM-14 AML cells with IC50 values b1 nM. Furthermore, the viability of drug-resistant AML cells harboring the D835Y and F691 L mutations were potently inhibited. In vivo efficacy studies in mice demonstrated that the compounds could drastically reduce AML proliferation in mice. Interpretation: Compounds that inhibit FLT3 and downstream targets like Src (for example HSN431) are good leads for development as anti-AML agents