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We report a case of a 61-year-old Filipino-American male who developed pulmonary tuberculosis after travel to the Philippines. His history, presentation, imaging findings, and clinical course are presented as well as a discussion of the interesting imaging features in his case. Our case highlights the importance of having a high index of suspicion for tuberculosis in the setting of "bronchiectatic air bronchograms" as well as the value of computed tomography (CT) imaging in pulmonary tuberculosis. [ABSTRACT FROM AUTHOR]

The efficacy of an antibiotic support team (AST) has been demonstrated in both large teaching hospitals and smaller community hospitals. The usefulness of an AST in a medium-sized military hospital was investigated in the present study. Patients at least 18 years old hospitalized at the David Grant USAF Medical Center (DGMC) and receiving > or =1 of 17 specified antibiotics for > or =3 consecutive days were randomized to an educational intervention group or control group. Primary endpoints included antibiotic defined daily dose (DDD) per patient treatment course and days of antibiotic therapy (DOT) per patient. Fifty-two patients were analyzed from March to August 2006. DDD per patient treatment course was significantly lower in the intervention group, (6.7 +/- 7.6 vs. 12.9 +/- 16.3, p = 0.05). A trend toward fewer DOT per patient was seen in the intervention vs. control group. Implementation of an AST decreased the intensity of exposure to antibiotics. [ABSTRACT FROM AUTHOR]

Geophysical methods can provide three-dimensional (3D), spatially continuous estimates of soil moisture. However, point-to-point comparisons of geophysical properties to measure soil moisture data are frequently unsatisfactory, resulting in geophysics being used for qualitative purposes only. This is because (1) geophysics requires models that relate geophysical signals to soil moisture, (2) geophysical methods have potential uncertainties resulting from smoothing and artifacts introduced from processing and inversion, and (3) results from multiple geophysical methods are not easily combined within a single soil moisture estimation framework. To investigate these potential limitations, an irrigation experiment was performed wherein soil moisture was monitored through time, and several surface geophysical datasets indirectly sensitive to soil moisture were collected before and after irrigation: ground penetrating radar, electrical resistivity tomography (ERT), and frequency domain electromagnetics (FDEM). Data were exported in both raw and processed form, and then snapped to a common 3D grid to facilitate moisture prediction by standard calibration techniques, multivariate regression, and machine learning. A combination of inverted ERT data, raw FDEM, and inverted FDEM data was most informative for predicting soil moisture using a random regression forest model (one-thousand 60/40 training/test cross-validation folds produced root mean squared errors ranging from 0.025-0.046 cm 3 /cm 3 ). This cross-validated model was further supported by a separate evaluation using a test set from a physically separate portion of the study area. Machine learning was conducive to a semi-automated model-selection process that could be used for other sites and datasets to locally improve accuracy., Competing Interests: CONFLIC OF INTEREST The authors declare no conflict of interest.

Groundwater/surface-water (GW/SW) exchange and hyporheic processes are topics receiving increasing attention from the hydrologic community. Hydraulic, chemical, temperature, geophysical, and remote sensing methods are used to achieve various goals (e.g., inference of GW/SW exchange, mapping of bed materials, etc.), but the application of these methods is constrained by site conditions such as water depth, specific conductance, bed material, and other factors. Researchers and environmental professionals working on GW/SW problems come from diverse fields and rarely have expertise in all available field methods; hence there is a need for guidance to design field campaigns and select methods that both contribute to study goals and are likely to work under site-specific conditions. Here, we present the spreadsheet-based GW/SW-Method Selection Tool (GW/SW-MST) to help practitioners identify methods for use in GW/SW and hyporheic studies. The GW/SW-MST is a Microsoft Excel-based decision support tool in which the user selects answers to questions about GW/SW-related study goals and site parameters and characteristics. Based on user input, the tool indicates which methods from a toolbox of 32 methods could potentially contribute to achieving the specified goals at the site described., (© 2022 National Ground Water Association. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

We present a geostatistics-based stochastic salinity estimation framework for the Montebello Oil Field that capitalizes on available total dissolved solids (TDS) data from groundwater samples as well as electrical resistivity (ER) data from borehole logging. Data from TDS samples (n = 4924) was coded into an indicator framework based on falling below four selected thresholds (500, 1000, 3000, and 10,000 mg/L). Collocated TDS-ER data from the surrounding groundwater basin were then employed to produce a kernel density estimator to establish conditional probabilities for ER data (n = 8 boreholes) falling below the selected TDS thresholds within the Montebello Oil Field area. Directional variograms were estimated from these indicator coded data, and 500 TDS realizations from conditional indicator simulation were generated for the subsurface region above the Montebello Oil Field reservoir. Simulations were summarized as 3D maps of median TDS, most likely salinity class, and probability for exceeding each of the specified TDS thresholds. Results suggested TDS was below 500 mg/L in most of the study area, with a trend toward higher values (500 to 1000 mg/L) to the southwest; consistent with the average regional groundwater flow direction. Discrete localized zones of TDS greater than 1000 mg/L were observed, with one of these zones in the greater than 10,000 mg/L range; however, these areas were not prevalent. The probabilistic approach used here is adaptable and is readily modified to include additional data and types and can be employed in time-lapse salinity modeling through Bayesian updating., (Published 2021. This article is a U.S. Government work and is in the public domain in the USA. Groundwater published by Wiley Periodicals LLC on behalf of National Ground Water Association.)

Groundwater discharge generates streamflow and influences stream thermal regimes. However, the water quality and thermal buffering capacity of groundwater depends on the aquifer source-depth. Here, we pair multi-year air and stream temperature signals to categorize 1729 sites across the continental United States as having major dam influence, shallow or deep groundwater signatures, or lack of pronounced groundwater (atmospheric) signatures. Approximately 40% of non-dam stream sites have substantial groundwater contributions as indicated by characteristic paired air and stream temperature signal metrics. Streams with shallow groundwater signatures account for half of all groundwater signature sites and show reduced baseflow and a higher proportion of warming trends compared to sites with deep groundwater signatures. These findings align with theory that shallow groundwater is more vulnerable to temperature increase and depletion. Streams with atmospheric signatures tend to drain watersheds with low slope and greater human disturbance, indicating reduced stream-groundwater connectivity in populated valley settings.

Freshwater lenses underlying small ocean islands exhibit spatial variability and temporal fluctuations in volume, influencing ecologic management. For example, The Palmyra Atoll National Wildlife Refuge harbors one of the few surviving native stands of Pisonia grandis in the central Pacific Ocean, yet these trees face pressure from groundwater salinization, with little basic groundwater data to guide decision making. Adding to natural complexity, the geology of Palmyra was heavily altered by dredge and fill activities. Our study based at this atoll combines geophysical and hydrological field measurements from 2008 to 2019 with groundwater modeling to study the drivers of observed freshwater lens dynamics. Electromagnetic induction (EMI) field data were collected on the main atoll islands over repeat transects in 2008 following 'strong' La Niña conditions (wet) and in 2016 during 'very strong' El Niño conditions (dry). Shallow monitoring wells were installed adjacent to the geophysical transects in 2013 and screened within the fresh/saline groundwater transition zone. Temporal EMI and monitoring well data showed a strong contraction of the freshwater lens in response to El Niño conditions, and indicated a thicker lens toward the ocean side, an opposite spatial pattern to that observed for many other Pacific islands. On an outer islet where a stand of mature Pisonia trees exist, EMI surveys revealed only a thin (<3 m from land surface) layer of brackish groundwater during El Niño. Numerical groundwater simulations were performed for a range of permeability distributions and climate conditions at Palmyra. Results revealed that the observed atypical lens asymmetry is likely due to more efficient submarine groundwater discharge on the lagoon side as a result of lagoon dredging and filling with high-permeability material. Simulations also predict large decreases (40%) in freshwater lens volume during dry cycles and highlight threats to the Pisonia trees, yielding insight for atoll ecosystem management worldwide., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Releases of oil and gas (OG) wastewaters can have complex effects on stream-water quality and downstream organisms, due to sediment-water interactions and groundwater/surface water exchange. Previously, elevated concentrations of sodium (Na), chloride (Cl), barium (Ba), strontium (Sr), and lithium (Li), and trace hydrocarbons were determined to be key markers of OG wastewater releases when combined with Sr and radium (Ra) isotopic compositions. Here, we assessed the persistence of an OG wastewater spill in a creek in North Dakota using a combination of geochemical measurements and modeling, hydrologic analysis, and geophysical investigations. OG wastewater comprised 0.1 to 0.3% of the stream-water compositions at downstream sites in February and June 2015 but could not be quantified in 2016 and 2017. However, OG-wastewater markers persisted in sediments and pore water for 2.5 years after the spill and up to 7.2-km downstream from the spill site. Concentrations of OG wastewater constituents were highly variable depending on the hydrologic conditions. Electromagnetic measurements indicated substantially higher electrical conductivity under the bank adjacent to a seep 7.2 km downstream from the spill site. Geomorphic investigations revealed mobilization of sediment is an important contaminant transport process. Labile Ba, Ra, Sr, and ammonium (NH 4 ) concentrations extracted from sediments indicated sediments are a long-term reservoir of these constituents, both in the creek and on the floodplain. Using the drivers of ecological effects identified at this intensively studied site we identified 41 watersheds across the North Dakota landscape that may be subject to similar episodic inputs from OG wastewater spills. Effects of contaminants released to the environment during OG waste management activities remain poorly understood; however, analyses of Ra and Sr isotopic compositions, as well as trace inorganic and organic compound concentrations at these sites in pore-water provide insights into potentials for animal and human exposures well outside source-remediation zones., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

A new version of the computer program FLASH (Flow-Log Analysis of Single Holes) is presented for the analysis of borehole vertical flow logs to estimate fracture (or layer) transmissivities and far-field hydraulic heads. The program is written in R, an open-source environment. All previous features have been retained and new features incorporated including more rigorous parameter estimation, uncertainty analysis, and improved data import. The program has a dynamic user interface compatible with most operating systems., (Published 2020. This article is a U.S. Government work and is in the public domain in the USA.)

The hydrogeology below large surface water features such as rivers and estuaries is universally under-informed at the long reach to basin scales (tens of km+). This challenge inhibits the accurate modeling of fresh/saline groundwater interfaces and groundwater/surface water exchange patterns at management-relevant spatial extents. Here we introduce a towed, floating transient electromagnetic (TEM) system (i.e. FloaTEM) for rapid (up to 15 km/h) high resolution electrical mapping of the subsurface below large water bodies to depths often a factor of 10 greater than other towed instruments. The novel FloaTEM system is demonstrated at a range of diverse 4th through 6th-order riverine settings across the United States including 1) the Farmington River, near Hartford, Connecticut; 2) the Upper Delaware River near Barryville, New York; 3) the Tallahatchie River near Shellmound, Mississippi; and, 4) the Eel River estuary, on Cape Cod, near Falmouth, Massachusetts. Airborne frequency-domain electromagnetic and land-based towed TEM data are also compared at the Tallahatchie River site, and streambed geologic scenarios are explored with forward modeling. A range of geologic structures and pore water salinity interfaces were identified. Process-based interpretation of the case study data indicated FloaTEM can resolve varied sediment-water interface materials, such as the accumulation of fines at the bottom of a reservoir and permeable sand/gravel riverbed sediments that focus groundwater discharge. Bedrock layers were mapped at several sites, and aquifer confining units were defined at comparable resolution to airborne methods. Terrestrial fresh groundwater discharge with flowpaths extending hundreds of meters from shore was also imaged below the Eel River estuary, improving on previous hydrogeological characterizations of that nutrient-rich coastal exchange zone. In summary, the novel FloaTEM system fills a critical gap in our ability to characterize the hydrogeology below surface water features and will support more accurate prediction of groundwater/surface water exchange dynamics and fresh-saline groundwater interfaces., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Fiber-optic distributed temperature sensing (FO-DTS) has proven to be a transformative technology for the hydrologic sciences, with application to diverse problems including hyporheic exchange, groundwater/surface-water interaction, fractured-rock characterization, and cold regions hydrology. FO-DTS produces large, complex, and information-rich datasets. Despite the potential of FO-DTS, adoption of the technology has been impeded by lack of tools for data processing, analysis, and visualization. New tools are needed to efficiently and fully capitalize on the information content of FO-DTS datasets. To this end, we present DTSGUI, a public-domain Python-based software package for editing, parsing, processing, statistical analysis, georeferencing, and visualization of FO-DTS data., (© 2019, National Ground Water Association.)

In cooperation with the U.S. Environmental Protection Agency (EPA), the U.S. Geological Survey (USGS) collected numerous types of geophysical data at a site in Fredericktown, Missouri, in June 2018. Various geophysical surveys were collectively used to help evaluate the overall suitability of the site for use as a mine waste-soil and sediment repository, and to evaluate the suite of geophysical methods for rapid collection and preliminary assessment of sites with shallow sediments. Land-based geophysical methods, which included frequency-domain electromagnetic induction (FDEM), electrical resistivity tomography (ERT), horizontal-to-vertical spectral ratio passive seismic (HVSR), and shear-wave refraction, were used to determine the depths to crystalline bedrock and characterize the overlying unconsolidated sediments (or regolith). Water-borne FDEM profiles and forward-looking infrared (FLIR) thermal image surveys were conducted along the Fredericktown City Lake shoreline to identify locations of potential interactions between groundwater and surface water. Sediment temperature profilers were installed at two locations along the shoreline to characterize shallow unconsolidated sediment thermal properties and support the interpretation of the other geophysical surveys. Geophysical reconnaissance methods including the FDEM and HVSR methods, were used to rapidly evaluate the vertical and lateral extent of overburden, or unconsolidated sediments, overlying the bedrock at the site. The results of these methods were compared to reference geophysical methods of ERT and shear-wave refraction surveys that have greater accuracy and are more labor intensive and time-consuming. A goal of the project was the evaluation of the validity and reliability of this suite of reconnaissance geophysical methods as a means by which shallow (less than 3 meters (m)) sediments can be rapidly assessed. Two orthogonal ERT survey profiles, which used 28 electrodes spaced 1 m apart in dipole-dipole and combined Wenner-Schlumberger configurations, were collected to determine the subsurface resistivity. The results were inverted to produce electrical resistivity profiles that were compared to the FDEM and HVSR survey results. The FDEM data were collected along cleared paths through the proposed disposal cell locations. The data were inverted to generate depth-dependent estimates of electrical conductivity along the transects. An analysis of the depth of investigation (DOI) indicated the FDEM imaged to depths of about 3 m below land surface. The ERT, FDEM, and HVSR indicated the depth to crystalline bedrock was approximately 1.5 m below land surface with shallower and deeper areas. Results from this investigation indicate this suite of methods will likely perform well at sites with shallow depths to bedrock and strong conductivity and acoustic impedance contrasts, where the FDEM and HVSR methods can provide estimates of the depth to bedrock, and ERT and shear-wave refraction surveys might not be worth the added time and expense.

River to floodplain hydrologic connectivity is strongly enhanced by beaver- (Castor canadensis) engineered channel water diversions. The hydroecological impacts are wide ranging and generally positive, however, the hydrogeochemical characteristics of beaver-induced flowpaths have not been thoroughly examined. Using a suite of complementary ground- and drone-based heat tracing and remote sensing methodology we characterized the physical template of beaver-induced floodplain exchange for two alluvial mountain streams near Crested Butte, Colorado, USA. A flowpath-oriented perspective to water quality sampling allowed characterization of the chemical evolution of channel water diverted through floodplain beaver ponds and ultimately back to the channel in 'beaver pond return flows'. Subsurface return flow seepages were universally suboxic, while ponds and surface return flows showed a range of oxygen concentration due to in-situ photosynthesis and atmospheric mixing. Median concentrations of reduced metals: manganese (Mn), iron (Fe), aluminum (Al), and arsenic (As) were substantially higher along beaver-induced flowpaths than in geologically controlled seepages and upstream main channel locations. The areal footprint of reduced return seepage flowpaths were imaged with surface electromagnetic methods, indicating extensive zones of high-conductivity shallow groundwater flowing back toward the main channels and emerging at relatively warm bank seepage zones observed with infrared. Multiple-depth redox dynamics within one focused seepage zone showed coupled variation over time, likely driven by observed changes in seepage rate that may be controlled by pond stage. High-resolution times series of dissolved Mn and Fe collected downstream of the beaver-impacted reaches demonstrated seasonal dynamics in mixed river metal concentrations. Al time series concentrations showed proportional change to Fe at the smaller stream location, indicating chemically reduced flowpaths were sourcing Al to the channel. Overall our results indicated beaver-induced floodplain exchanges create important, and perhaps dominant, transport pathways for floodplain metals by expanding chemically-reduced zones paired with strong advective exchange., (Published by Elsevier B.V.)

Quantitative evaluation of groundwater/surface water exchange dynamics is universally challenging in large river systems, because existing methodology often does not yield spatially-distributed data and is difficult to apply in deeper water. Here we apply a combined near-surface geophysical and direct groundwater chemical toolkit to refine fresh groundwater discharge estimates to the Colorado River through a 4-km 2 wetland that borders the town of Moab, Utah, USA. Preliminary characterization of raw electromagnetic imaging (EMI) data, collected by kayak and by walking, was used to guide additional direct-contact electrical measurements and installation of new monitoring wells. Chemical data from the wells strongly supported the EMI spatial characterization of preferential fresh groundwater discharge embedded in natural brine groundwaters and weighted to the southern wetland section. Inversion of the EMI data revealed sub-meter scale detail regarding bulk electrical conductivity zonation across approximately 15.5 km of transects, collected in only 3 days. This electrical detail indicates processes such as salinization of the unsaturated zone and direct discharge through the Colorado River sediments and a tributary creek bed. Overall, the study contributed to a substantial reduction in fresh groundwater discharge estimates previously made using sparse existing well data and a simplified assumption of diffuse fresh groundwater discharge below the entire wetland. EMI will likely become a widely used tool in systems with natural electrical contrast as groundwater/surface water hydrogeologists continue to recognize the prevalence of preferential groundwater discharge processes., (© 2019, National Ground Water Association.)

The characterization of pore-space connectivity in porous media at the sediment/water interface is critical in understanding contaminant transport and reactive biogeochemical processes in zones of groundwater and surface-water exchange. Previous in situ studies of dual-domain (i.e., mobile/less-mobile porosity) systems have been limited to solute tracer injections at scales of meters to hundreds of meters and subsequent numerical model parameterization using fluid concentration histories. Pairing fine-scale (e.g., sub-meter) geoelectrical measurements with fluid tracer data over time alleviates dependence on flowpath-scale experiments, enabling spatially targeted characterization of shallow sediment/water interface media where biogeochemical reactivity is often high. The Dual-Domain Porosity Apparatus is a field-tested device capable of variable rate-controlled downward flow experiments. The Dual-Domain Porosity Apparatus facilitates inference of dual-domain parameters, i.e., mobile/less-mobile exchange rate coefficient and the ratio of less mobile to mobile porosity. The Dual-Domain Porosity Apparatus experimental procedure uses water electrical conductivity as a conservative tracer of differential loading and flushing of pore spaces within the region of measurement. Variable injection rates permit the direct quantification of the flow-dependence of dual-domain parameters, which has been theorized for decades but remains challenging to assess using existing experimental methodologies., (Published 2018. This article is a U.S. Government work and is in the public domain in the USA.)

Streams strongly influenced by groundwater discharge may serve as "climate refugia" for sensitive species in regions of increasingly marginal thermal conditions. The main goal of this study is to develop paired air and stream water annual temperature signal analysis techniques to elucidate the relative groundwater contribution to stream water and the effective groundwater flowpath depth. Groundwater discharge to streams attenuates surface water temperature signals, and this attenuation can be diagnostic of groundwater gaining systems. Additionally, discharge from shallow groundwater flowpaths can theoretically transfer lagged annual temperature signals from aquifer to stream water. Here we explore this concept using multi-year temperature records from 120 stream sites located across 18 mountain watersheds of Shenandoah National Park, VA, USA and a coastal watershed in Massachusetts, USA. Both areas constitute important cold-water habitat for native brook trout (Salvelinus fontinalis). Observed annual temperature signals indicate a dominance of shallow groundwater discharge to streams in the National Park, in contrast to the coastal watershed that has strong, apparently deeper, groundwater influence. The average phase lag from air to stream signals in Shenandoah National Park is 11 d; however, extended lags of approximately 1 month were observed in a subset of streams. In contrast, the coastal stream has pronounced attenuation of annual temperature signals without notable phase lag. To better understand these observed differences in signal characteristics, analytical and numerical models are used to quantify mixing of the annual temperature signals of surface and groundwater. Simulations using a total heat budget numerical model indicate groundwater-induced annual temperature signal phase lags are likely to show greater downstream propagation than the related signal amplitude attenuation. The measurement of multi-seasonal paired air and water temperatures offers great promise toward understanding catchment processes and informing current cold-water habitat management at ecologically-relevant scales., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Noninvasive geophysical estimation of soil moisture has potential to improve understanding of flow in the unsaturated zone for problems involving agricultural management, aquifer recharge, and optimization of landfill design and operations. In principle, several geophysical techniques (e.g., electrical resistivity, electromagnetic induction, and nuclear magnetic resonance) offer insight into soil moisture, but data-analysis tools are needed to "translate" geophysical results into estimates of soil moisture, consistent with (1) the uncertainty of this translation and (2) direct measurements of moisture. Although geostatistical frameworks exist for this purpose, straightforward and user-friendly tools are required to fully capitalize on the potential of geophysical information for soil-moisture estimation. Here, we present MoisturEC, a simple R program with a graphical user interface to convert measurements or images of electrical conductivity (EC) to soil moisture. Input includes EC values, point moisture estimates, and definition of either Archie parameters (based on experimental or literature values) or empirical data of moisture vs. EC. The program produces two- and three-dimensional images of moisture based on available EC and direct measurements of moisture, interpolating between measurement locations using a Tikhonov regularization approach., (Published 2018. This article is a U.S. Government work and is in the public domain in the USA.)

Brook trout (Salvelinus fontinalis) spawn in fall and overwintering egg development can benefit from stable, relatively warm temperatures in groundwater-seepage zones. However, eggs are also sensitive to dissolved oxygen concentration, which may be reduced in discharging groundwater (i.e., seepage). We investigated a 2 km reach of the coastal Quashnet River in Cape Cod, Massachusetts, USA, to relate preferred fish spawning habitats to geology, geomorphology, and discharging groundwater geochemistry. Thermal reconnaissance methods were used to locate zones of rapid groundwater discharge, which were predominantly found along the central channel of a wider stream valley section. Pore-water chemistry and temporal vertical groundwater flux were measured at a subset of these zones during field campaigns over several seasons. Seepage zones in open-valley sub-reaches generally showed suboxic conditions and higher dissolved solutes compared to the underlying glacial outwash aquifer. These discharge zones were cross-referenced with preferred brook trout redds and evaluated during 10 years of observation, all of which were associated with discrete alcove features in steep cutbanks, where stream meander bends intersect the glacial valley walls. Seepage in these repeat spawning zones was generally stronger and more variable than in open-valley sites, with higher dissolved oxygen and reduced solute concentrations. The combined evidence indicates that regional groundwater discharge along the broader valley bottom is predominantly suboxic due to the influence of near-stream organic deposits; trout show no obvious preference for these zones when spawning. However, the meander bends that cut into sandy deposits near the valley walls generate strong oxic seepage zones that are utilized routinely for redd construction and the overwintering of trout eggs. Stable water isotopic data support the conclusion that repeat spawning zones are located directly on preferential discharges of more localized groundwater. In similar coastal systems with extensive valley peat deposits, the specific use of groundwater-discharge points by brook trout may be limited to morphologies such as cutbanks, where groundwater flow paths do not encounter substantial buried organic material and remain oxygen-rich., Competing Interests: Competing interests. The authors declare that they have no conflict of interest.

Geophysical tools have much to offer users in environmental, water resource, and geotechnical fields; however, techniques such as electrical resistivity imaging (ERI) are often oversold and/or overinterpreted due to a lack of understanding of the limitations of the techniques, such as the appropriate depth intervals or resolution of the methods. The relationship between ERI data and resistivity is nonlinear; therefore, these limitations depend on site conditions and survey design and are best assessed through forward and inverse modeling exercises prior to field investigations. In this approach, proposed field surveys are first numerically simulated given the expected electrical properties of the site, and the resulting hypothetical data are then analyzed using inverse models. Performing ERI forward/inverse modeling, however, requires substantial expertise and can take many hours to implement. We present a new spreadsheet-based tool, the Scenario Evaluator for Electrical Resistivity (SEER), which features a graphical user interface that allows users to manipulate a resistivity model and instantly view how that model would likely be interpreted by an ERI survey. The SEER tool is intended for use by those who wish to determine the value of including ERI to achieve project goals, and is designed to have broad utility in industry, teaching, and research., (© 2017, National Ground Water Association.)

A new version of the computer program 1DTempPro extends the original code to include new capabilities for (1) automated parameter estimation, (2) layer heterogeneity, and (3) time-varying specific discharge. The code serves as an interface to the U.S. Geological Survey model VS2DH and supports analysis of vertical one-dimensional temperature profiles under saturated flow conditions to assess groundwater/surface-water exchange and estimate hydraulic conductivity for cases where hydraulic head is known., (Published 2015. This article is a U.S. Government work and is in the public domain in the USA.)

Biostimulation is increasingly used to accelerate microbial remediation of recalcitrant groundwater contaminants. Effective application of biostimulation requires successful emplacement of amendment in the contaminant target zone. Verification of remediation performance requires postemplacement assessment and contaminant monitoring. Sampling-based approaches are expensive and provide low-density spatial and temporal information. Time-lapse electrical resistivity tomography (ERT) is an effective geophysical method for determining temporal changes in subsurface electrical conductivity. Because remedial amendments and biostimulation-related biogeochemical processes often change subsurface electrical conductivity, ERT can complement and enhance sampling-based approaches for assessing emplacement and monitoring biostimulation-based remediation. Field studies demonstrating the ability of time-lapse ERT to monitor amendment emplacement and behavior were performed during a biostimulation remediation effort conducted at the Department of Defense Reutilization and Marketing Office (DRMO) Yard, in Brandywine, Maryland, United States. Geochemical fluid sampling was used to calibrate a petrophysical relation in order to predict groundwater indicators of amendment distribution. The petrophysical relations were field validated by comparing predictions to sequestered fluid sample results, thus demonstrating the potential of electrical geophysics for quantitative assessment of amendment-related geochemical properties. Crosshole radar zero-offset profile and borehole geophysical logging were also performed to augment the data set and validate interpretation. In addition to delineating amendment transport in the first 10 months after emplacement, the time-lapse ERT results show later changes in bulk electrical properties interpreted as mineral precipitation. Results support the use of more cost-effective surface-based ERT in conjunction with limited field sampling to improve spatial and temporal monitoring of amendment emplacement and remediation performance., (Published 2014. This article is a U.S. Government work and is in the public domain in the USA.)

We apply fluid-replacement logging in arsenic-contaminated regions of Bangladesh using a low-cost, down-well fluid conductivity logging tool to detect leaks in the cased section of wells. The fluid-conductivity tool is designed for the developing world: it is lightweight and easily transportable, operable by one person, and can be built for minimal cost. The fluid-replacement test identifies leaking casing by comparison of fluid conductivity logs collected before and after spiking the wellbore with a sodium chloride tracer. Here, we present results of fluid-replacement logging tests from both leaking and non-leaking casing from wells in Araihazar and Munshiganj, Bangladesh, and demonstrate that the low-cost tool produces measurements comparable to those obtained with a standard geophysical logging tool. Finally, we suggest well testing procedures and approaches for preventing casing leaks in Bangladesh and other developing countries., (© 2014, National Ground Water Association.)

A new computer program, 1DTempPro, is presented for the analysis of vertical one-dimensional (1D) temperature profiles under saturated flow conditions. 1DTempPro is a graphical user interface to the U.S. Geological Survey code Variably Saturated 2-Dimensional Heat Transport (VS2DH), which numerically solves the flow and heat-transport equations. Pre- and postprocessor features allow the user to calibrate VS2DH models to estimate vertical groundwater/surface-water exchange and also hydraulic conductivity for cases where hydraulic head is known., (Published 2013. This article is a U.S. Government work and is in the public domain in the USA.)

A small-diameter nuclear magnetic resonance (NMR) logging tool has been developed and field tested at various sites in the United States and Australia. A novel design approach has produced relatively inexpensive, small-diameter probes that can be run in open or PVC-cased boreholes as small as 2 inches in diameter. The complete system, including surface electronics and various downhole probes, has been successfully tested in small-diameter monitoring wells in a range of hydrogeological settings. A variant of the probe that can be deployed by a direct-push machine has also been developed and tested in the field. The new NMR logging tool provides reliable, direct, and high-resolution information that is of importance for groundwater studies. Specifically, the technology provides direct measurement of total water content (total porosity in the saturated zone or moisture content in the unsaturated zone), and estimates of relative pore-size distribution (bound vs. mobile water content) and hydraulic conductivity. The NMR measurements show good agreement with ancillary data from lithologic logs, geophysical logs, and hydrogeologic measurements, and provide valuable information for groundwater investigations., (© 2013, National Ground Water Association.)

Groundwater discharge locations along the upper Delaware River, both discrete bank seeps and diffuse streambed upwelling, may create thermal niche environments that benefit the endangered dwarf wedgemussel (Alasmidonta heterodon). We seek to identify whether discrete or diffuse groundwater inflow is the dominant control on refugia. Numerous springs and seeps were identified at all locations where dwarf wedgemussels still can be found. Infrared imagery and custom high spatial resolution fiber-optic distributed temperature sensors reveal complex thermal dynamics at one of the seeps with a relatively stable, cold groundwater plume extending along the streambed/water-column interface during midsummer. This plume, primarily fed by a discrete bank seep, was shown through analytical and numerical heat-transport modeling to dominate temperature dynamics in the region of potential habitation by the adult dwarf wedgemussel.

We describe a computer-controlled tactile stimulator for use in human psychophysical and monkey neurophysiological studies of 3D shape perception. The stimulator is constructed primarily of commercially available parts, as well as a few custom-built pieces for which we will supply diagrams upon request. There are two components to the stimulator: a tactile component and a hand positioner component. The tactile component consists of multiple stimulating units that move about in a Cartesian plane above the restrained hand. Each stimulating unit contains a servo-controlled linear motor with an attached small rotary stepper motor, allowing arbitrary stimulus shapes to contact the skin through vibration, static indentation, or scanning. The hand positioner component modifies the conformation of the restrained hand through a set of mechanical linkages under motorized control. The present design controls the amount of spread between digits 2 and 3, the spread between digits 4 and 3, and the degree to which digit 3 is flexed or extended, thereby simulating different conformations of the hand in contact with objects. This design is easily modified to suit the needs of the experimenter. Because the two components of the stimulator are independently controlled, the stimulator allows for parametric study of the mechanoreceptive and proprioceptive contributions to 3D tactile shape perception.

While the existence of relatively fresh groundwater sequestered within permeable, porous sediments beneath the Atlantic continental shelf of North and South America has been known for some time, these waters have never been assessed as a potential resource. This fresh water was likely emplaced during Pleistocene sea-level low stands when the shelf was exposed to meteoric recharge and by elevated recharge in areas overrun by the Laurentide ice sheet at high latitudes. To test this hypothesis, we present results from a high-resolution paleohydrologic model of groundwater flow, heat and solute transport, ice sheet loading, and sea level fluctuations for the continental shelf from New Jersey to Maine over the last 2 million years. Our analysis suggests that the presence of fresh to brackish water within shallow Miocene sands more than 100 km offshore of New Jersey was facilitated by discharge of submarine springs along Baltimore and Hudson Canyons where these shallow aquifers crop out. Recharge rates four times modern levels were computed for portions of New England's continental shelf that were overrun by the Laurentide ice sheet during the last glacial maximum. We estimate the volume of emplaced Pleistocene continental shelf fresh water (less than 1 ppt) to be 1300 km(3) in New England. We also present estimates of continental shelf fresh water resources for the U.S. Atlantic eastern seaboard (10(4) km(3)) and passive margins globally (3 x 10(5) km(3)). The simulation results support the hypothesis that offshore fresh water is a potentially valuable, albeit nonrenewable resource for coastal megacities faced with growing water shortages.

Background: Acute increases in serum inorganic phosphorus (Pi) up to 4.75 mmol/l in the absence of hypocalcemia and tissue deposition of calcium phosphate were noted in 3 patients receiving liposomal amphotericin B (L-AMB). We investigated L-AMB as a possible cause of pseudohyperphosphatemia., Methods: Serum samples from the index patient were analyzed for Pi content by our laboratory's primary analyzer (Synchron LX20) and by an alternate analyzer (Vitros). Clear and lipemic serum pools, and normal saline, were spiked with L-AMB and analyzed by the LX20 Pi method. Ultrafiltration studies were performed on patient and spiked sera., Results: Increased Pi values were obtained only from the LX20 analyzer. There was a direct linear relationship between the concentration of L-AMB in the spiked samples and the LX20 Pi results, indicating a 0.9 mmol/l Pi increase for every 100 mg/l increase in L-AMB. Ultrafiltration normalized the Pi results., Conclusion: Serum Pi results may be falsely increased in patients receiving L-AMB when measured by the LX20 analyzer. This novel cause of pseudohyperphosphatemia is due to interference of L-AMB with the method and is corrected by ultrafiltration of the specimen. Since the LX20 analyzer is widely used by the clinical laboratories clinicians and laboratory personnel should recognize this interference in order to avoid unnecessary diagnostic procedures and interventions.

The regiochemical outcome of Pictet-Spengler cyclization reactions directed toward the preparation of the pentacyclic core of the ecteinascidin class of antitumor antibiotics has been investigated on two different phenolic substrates. In one substrate, the assistance of an incipient benzylamine group at C-4 is postulated to direct the cyclization in favor of the pentacyclic framework of ET-743, which bears a hydroxyl group at C-18. Conversely, cyclization of an alternative substrate lacking a heteroatom at C-4 favors the opposite regiochemical outcome, primarily affording an unnatural pentacyclic core bearing a hydroxyl group at C-16.

We investigate the position invariant receptive field properties of neurons in the macaque second somatosensory (SII) cortical region. Previously we reported that many SII region neurons show orientation tuning in the center of multiple finger pads of the hand and further that the tuning is similar on different pads, which can be interpreted as position invariance. Here we study the receptive field properties of a single finger pad for a subset (n = 61) of those 928 neurons, using a motorized oriented bar that we positioned at multiple locations across the pad. We calculate both vector fields and linear receptive fields of the finger pad to characterize the receptive field properties that give rise to the tuning, and we perform an additional regression analysis to quantify linearity, invariance, or both in individual neurons. We show that orientation tuning of SII region neurons is based on a variety of mechanisms. For some neurons, the tuning is explained by simple excitatory regions, simple inhibitory regions, or some combination of these structures. However, a large fraction of the neurons (n = 20 of 61, 33%) show position invariance that is not explained well by their linear receptive fields. Finding invariance within a finger pad, coupled with the previous result of similar tuning on different pads, indicates that some SII region neurons may exhibit similar tuning throughout large regions of the hand. We hypothesize that invariant neurons play an important role in tactile form recognition.

Analogues of the tetrahydroisoquinoline family of antitumor antibiotics, 3-epi-jorumycin (3) and 3-epi-renieramycin G (4), in addition to their respective parent natural products (-)-jorumycin (1) and (-)-renieramycin G (2) were evaluated against both human colon (HCT-116) and human lung (A549) cancer cell lines. (-)-Jorumycin (1) displayed potent growth inhibition with GI50 values in the low nanomolar range (1.9-24.3 nM), while compounds 2-4 were found to be substantially less cytotoxic (GI50 0.6-14.0 microM).

The detailed structure of multidigit receptive fields (RFs) in somatosensory cortical areas such as the SII region has not been investigated previously using systematically controlled stimuli. Recently (Fitzgerald et al., 2004), we showed that the SII region comprises three adjoining fields: posterior, central, and anterior. Here we characterize the RF structures of the 928 neurons that were reported in that study using a motorized oriented bar that was indented into the 12 finger pads of digits 2-5. Most (81%) of the neurons were responsive to the oriented bar stimuli, and 81% of those neurons had RFs that spanned multiple digits. Furthermore, the RFs varied greatly in size, shape, and complexity. Some RFs contained only excitatory finger pads, some contained only inhibitory pads, and some contained both types of pads. A subset of the neurons (23%) showed orientation tuning within one or more pads. The RFs spread across different digits more than within individual digits, and the responsive finger pads for a given neuron tended to cluster together within the hand. Distal and lateral finger pads were better represented than proximal and medial finger pads. Furthermore, neurons in the posterior, central, and anterior SII region fields contained different proportions of RF types. These results collectively indicate that most SII region neurons are selective for different stimulus forms either within single finger pads or across multiple pads. We hypothesize that these RFs represent the kernels underlying the representation of tactile shape.

Orientation tuning has been studied extensively in the visual system, but little is known about it in the somatosensory system. Here we investigate tuning in the second somatosensory (SII) region using a motorized stimulator that presented a small oriented bar to the 12 finger pads of digits 2-5 (D2-D5) of the macaque monkey. A subset (23%; n = 218) of the 928 SII region neurons [the same 928 neurons studied by Fitzgerald et al. (2004, 2006)] exhibited tuning, and most of these were tuned on one or two finger pads. All eight 22.5 degrees separated orientations were represented as the preferred orientation of multiple neurons, although not necessarily in equal numbers. A measure of bandwidth indicated that tuning in the SII region is sharp and is similar to the tuning observed in visual cortical areas. In addition, two-dimensional Gaussians that were fit to the tuning curves had very high r2 values, indicating that most tuning curves are both unimodal and symmetrical with respect to their preferred orientation. Most tuned neurons had additional untuned pads, although the responsiveness of these pads tended to be less than the responsiveness of tuned pads. Neurons with multiple tuned pads tended to have similar preferred orientations on their tuned pads, which can be interpreted as evidence for integration of information across fingers or as a form of positional invariance. Finally, comparison of the tuning properties showed that there are small but significant differences between the posterior, central, and anterior fields of the SII region.

The USGS conducted a geophysical investigation in support of a U.S. Naval Facilities Engineering Command, Southern Division field-scale biostimulation pilot project at Anoka County Riverfront Park (ACP), down-gradient of the Naval Industrial Reserve Ordnance Plant, Fridley, Minnesota. The goal of the pilot project is to evaluate subsurface injection of vegetable oil emulsion (VOE) to stimulate microbial degradation of chlorinated hydrocarbons. To monitor the emplacement and movement of the VOE and changes in water chemistry resulting from VOE dissolution and/or enhanced biological activity, the USGS acquired cross-hole radar zero-offset profiles, travel-time tomograms, and borehole geophysical logs during five site visits over 1.5 years. Analysis of pre- and postinjection data sets using petrophysical models developed to estimate VOE saturation and changes in total dissolved solids provides insights into the spatial and temporal distribution of VOE and ground water with altered chemistry. Radar slowness-difference tomograms and zero-offset slowness profiles indicate that the VOE remained close to the injection wells, whereas radar attenuation profiles and electromagnetic induction logs indicate that bulk electrical conductivity increased down-gradient of the injection zone, diagnostic of changing water chemistry. Geophysical logs indicate that some screened intervals were located above or below zones of elevated dissolved solids; hence, the geophysical data provide a broader context for interpretation of water samples and evaluation of the biostimulation effort. Our results include (1) demonstration of field and data analysis methods for geophysical monitoring of VOE biostimulation and (2) site-specific insights into the spatial and temporal distributions of VOE at the ACP.

The total synthesis of (-)-jorumycin (1) and (-)-renieramycin G (2) has been accomplished in 25 and 23 steps, respectively, from 5-benzyloxy-2,4-dimethoxy-3-methyl-benzyl alcohol. The synthesis features a substrate-tunable stereoselective intramolecular Pictet-Spengler-type reaction for the construction of the key pentacyclic core of both targets, bearing either the natural configuration or the epimeric configuration at C-3. With access to a C-3 epi-pentacyclic framework, 3-epi-jorumycin (32) and 3-epi-renieramycin G (34) were also successfully synthesized. Furthermore, preliminary biological evaluation of 3-epi-jorumycin (32), in addition to relevant synthetic intermediates, revealed that significant cytotoxicity had been retained in these compounds. Therefore, these early studies constitute the basis for a new structure activity relationship (SAR) investigation for this class of antitumor antibiotics.

Boreholes drilled through contaminated zones in fractured rock create the potential for vertical movement of contaminated ground water between fractures. The usual assumption is that purging eliminates cross contamination; however, the results of a field study conducted in a trichloroethylene (TCE) plume in fractured sandstone with a mean matrix porosity of 13% demonstrates that matrix-diffusion effects can be strong and persistent. A deep borehole was drilled to 110 m below ground surface (mbgs) near a shallow bedrock well containing high TCE concentrations. The borehole was cored continuously to collect closely spaced samples of rock for analysis of TCE concentrations. Geophysical logging and flowmetering were conducted in the open borehole, and a removable multilevel monitoring system was installed to provide hydraulic-head and ground water samples from discrete fracture zones. The borehole was later reamed to complete a well screened from 89 to 100 mbgs; persistent TCE concentrations at this depth ranged from 2100 to 33,000 microg/L. Rock-core analyses, combined with the other types of borehole information, show that nearly all of this deep contamination was due to the lingering effects of the downward flow of dissolved TCE from shallower depths during the few days of open-hole conditions that existed prior to installation of the multilevel system. This study demonstrates that transfer of contaminant mass to the matrix by diffusion can cause severe cross contamination effects in sedimentary rocks, but these effects generally are not identified from information normally obtained in fractured-rock investigations, resulting in potential misinterpretation of site conditions.

The detailed functional organization of the macaque second somatosensory cortex (SII) is not well understood. Here we report the results of a study of the functional organization of the SII hand region that combines microelectrode mapping using hand-held stimuli with single-unit recordings using a motorized, computer-controlled tactile oriented bar. The data indicate that the SII hand region extends approximately 10 mm in the anteroposterior (AP) dimension, primarily within the upper bank of the lateral sulcus. Furthermore, we find evidence that this region consists of multiple functional fields, with a central field containing neurons that are driven well by cutaneous stimuli, flanked by an anterior field and a posterior field that each contain neurons that are driven well by proprioceptive stimuli and less well by cutaneous stimuli. The anterior field extends approximately 4-5 mm AP, the central field extends approximately 3-4 mm, and the posterior field extends approximately 3 mm. Data from the motorized stimulator indicate that neurons in the central field are more responsive to oriented bars, more frequently exhibit orientation tuning, and have larger receptive fields than neurons in the anterior and posterior fields. We speculate that the three putative fields play different functional roles in tactile perception; the anterior and posterior fields process information that involves both proprioceptive and cutaneous input such as sensorimotor integration or stereognosis, whereas the central field processes primarily cutaneous information.

[reaction: see text]. A new method was developed for the stereoselective synthesis of alpha-substituted serine amino acids. The strategy utilizes a common enantiomerically enriched intermediate obtained through an enzymatic desymmetrization. A variety of amino acids were synthesized in good ee's through nucleophilic acetylide addition reactions and palladium-catalyzed Sonogashira couplings.

As part of an effort to probe the mechanism by which glycosyltransferases recognize glycoproteins and assemble the core structures of O-linked oligosaccharides, constrained glycopeptides, compounds 2 and 3, based on the alpha-N-acetylgalactosaminyl serine substructure 1, were designed. In this paper we describe a stereoselective preparation of protected versions of these compounds. A pig liver esterase-catalyzed enzymatic desymmetrization of a diacetate substrate, 10, was employed as a key component in the synthesis.

The first case of plexiform fibrohistiocytic tumor in the foot is presented in this article. The tumor developed on the dorsum of the left foot in a 14-year-old female. This tumor was originally described in 1988 by Enzinger and Zhang. Their study indicated that this tumor has a female predominance, median age of 14.5 years, 63% located in the upper extremities, 37.5% recurrence rate, and 3% metastasis rate. These tumors are very unique with a nodular pattern and a cellular component of histiocytes, fibroblasts, and multinucleated giant cells. Typically they are located within the deep dermis and subcutaneous tissue. Immunohistochemical preparations show that the tumor does not stain for S-100 protein, desmin, cytokeratin, factor VIII-related protein, or lysozyme. However, it does stain for alpha-1-antitrypsin, alpha-1-antichymotrypsin, alpha-smooth muscle-specific actin, vimentin, and CD68 antibody.

The common groundwater contaminant trichloroethylene (TCE), when given by oral gavage, can produce free radical species during metabolism. Furthermore, TCE end-stage metabolites, trichloroacetic acid and dichloroacetic acid, cause lipid peroxidation in mouse liver. The time courses of lipid peroxidation, free radical generation, and 8-hydroxydeoxyguanosine (8OHdG) formation were used to assess the level of oxidative stress in the liver of B6C3F1 mice dosed orally once daily, 5 days a week for 8 weeks at 0, 400, 800, and 1200 mg/kg TCE in corn oil. Peroxisomal proliferation, cell proliferation, and apoptosis were evaluated at selected times during the study. Lipid peroxidation, as measured by thiobarbituric acid-reactive substances (TBARS), was significantly elevated at the two highest dose levels of TCE on days 6 through 14 of the study. 8OHdG levels were statistically significant in the 1200 mg/kg/day group on days 2, 3, 10, 28, 49, and 56 only. The highest measured free radical load, 307% of oil control, occurred at day 6. A significant increase in cell and peroxisomal proliferation was observed during the same time period in the 1200 mg/kg/day group. Necrosis or an increase in apoptosis was not observed at any dose. The temporal relationship between oxidative stress and cellular response of proliferation, both of which occur and resolve within the same relative time period, suggests that TCE-induced mitogenesis may result from alteration in the liver microenvironment which offers a selective advantage for certain hepatocyte subpopulations.

Fluorescent dyes were used to mark and identify the tracks left by extracellular microelectrodes in neurophysiological experiments. Forty-two penetrations were made into the postcentral gyrus of 3 Macaque monkeys with electrodes coated with 1 of 5 fluorescent dyes (DiI, DiO, DiI-C5, PyPO, and Fast Blue). The electrodes were driven at rates ranging from 10 to 1000 microns/min, to a depth of about 4000 microns, where a small electrolytic lesion was made. Histological sections were viewed under fluorescent optics and the electrode tracks were reconstructed from the dye traces. Fluorescent traces (width 50-400 microns) were observed in 41 of 42 penetrations with 24 traces extending to the lesion site. Of the electrodes driven in less than 3 h, those coated with DiI (8/8) and DiI-C5 (8/8) left a trace to the lesion site, while 57% (4/7) of the DiO, 40% (2/5) of the Fast Blue and only 11% (1/9) of the PyPO tracks were fully marked. This method of marking penetrations can be used with any extracellular recording configuration, does not require tissue sections to be processed or stained, does not require electrical lesions, and causes no detectable tissue damage. Because the dyes fluoresce at different wavelengths, closely spaced tracks can be uniquely identified.

1. Patch clamp techniques were used to measure the ionic dependence of amiloride block of single mechanosensitive (MS) channels in frog (Xenopus laevis) oocytes. 2. The primary aim was to determine whether the difference in potency of amiloride block of MS channels in frog oocytes (IC50 = 0.5 mM) and chick auditory hair cells (IC50 = 50 microM) was due to the different ionic recording solutions. 3. Amiloride block of the oocyte MS channel does not vary significantly with complete substitution of external Na+ (i.e. 100 mM) with K+ in Ca(2+)-free recording solution (in both Na+ and K+ the IC50 = 0.5 mM). 4. A physiological concentration (1.8 mM) of external Ca2+ blocks the oocyte MS channel and reduces the potency of amiloride block (IC50 = 1.1 mM) without altering the voltage-dependence or the HIll coefficient (n = 1.8) of amiloride block. The reduction in potency can be explained by surface charge screening by Ca2+ which reduces the effective amiloride surface concentration. 5. The present results indicate that factors other than ionic recording conditions must underlie the difference in potency of amiloride block of MS channels in oocytes and auditory hair cells.

1. Patch clamp recording techniques have been used to compare the block caused by amiloride and some of its structural analogues of the mechanosensitive (MS) cation selective channel in frog (Xenopus laevis) oocytes. 2. Like amiloride, the amiloride analogues dimethylamiloride (DMA), benzamil and bromohexamethyleneamiloride (BrHMA) block the MS channel in a highly voltage-dependent manner. 3. All analogues tested were more potent blockers than amiloride with IC50's of 500 microM (amiloride), 370 microM (DMA), 95 microM (benzamil) and 34 microM (BrHMA). 4. Hill plots gave Hill coefficients of 2 (amiloride), 1.8 (DMA), 1 (benzamil) and 1.2 (BrHMA) indicating that the binding of two ligand molecules may be necessary for the block caused by amiloride, DMA and possibly BrHMA whereas only a single ligand molecule may be required for the block by benzamil. 5. The potential use of BrHMA as a light-activated, covalent label of the MS channel protein is discussed. 6. The amiloride analogue 'fingerprinting' of the blocking site on the MS channel indicates it is structurally different from previously described amiloride-sensitive ion transport pathways but may be related to the amiloride binding site on outer hair cells of the ear.

1. Patch clamp recording techniques have been used to investigate the block by amiloride of the mechanosensitive cation-selective channel in frog (Xenopus laevis) oocytes. 2. Cell-attached and outside-out patch recording configurations were employed to study the differences in block produced when amiloride was present at either the extracellular (external) or intracellular (internal) membrane face. 3. External amiloride causes a highly voltage-dependent 'flickery' block of single mechanosensitive channel currents in which inward mechanosensitive current recorded at negative potentials is reduced in amplitude but outward mechanosensitive current recorded at positive potentials is almost unaffected. 4. At -100 mV the apparent dissociation constant (Kd) for external amiloride block is 0.5 mM. The extracellular concentration dependence of amiloride block yields a Hill coefficient equal to 2, inconsistent with a single site blocking stoichiometry. 5. The shapes of current-voltage relationships measured in different external amiloride concentrations also indicate deviations from a simple channel plug model in which a single blocking cation is driven into the channel by the membrane potential. 6. Internal amiloride causes a voltage-independent 'flickery' block of mechanosensitive channel currents which equally reduces both inward and outward mechanosensitive currents. 7. The present data indicate that a minimum of two amiloride binding sites are necessary to predict external amiloride block. A model involving a voltage-dependent conformational change with subsequent voltage-independent co-operative binding of two amiloride molecules is found to explain the data. 8. The relevance of the present actions of amiloride on mechanosensitive channels is discussed in relation to reports of amiloride-inhibitable cation flux pathways involved in a number of basic physiological functions including mechanosensitivity of sensory cells, volume regulation and fertilization.

The Anxiety Symptoms Interview (ASI) is a diagnostic instrument designed to identify agoraphobia (with and without panic attacks), panic disorder, social phobia, and obsessive compulsive disorder according to DSM-III criteria. The present study evaluated the diagnostic validity of this instrument by examining the extent to which ASI diagnoses assigned to 73 clinic patients agreed with diagnoses determined by clinicians. Most kappa coefficients and other concordance indicators were in the acceptable range or above, a finding that held for diagnoses overall and for specific diagnoses of agoraphobia with panic attacks, social phobia, and obsessive compulsive disorder. However, none of the 73 patients had clinician-assigned diagnoses of panic disorder (that is, without agoraphobia) or agoraphobia without panic. Limitations and applications of the ASI are discussed.