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Background New pharmacotherapies to treat alcohol use disorders (AUD) are needed. Given the complex nature of AUD, there likely exist multiple novel drug targets. We, and others, have shown that the tetracycline drugs, minocycline and doxycycline, reduced ethanol (EtOH) drinking in mice. To test the hypothesis that suppression of high EtOH consumption is a general property of tetracyclines, we screened several derivatives for antidrinking activity using the Drinking-In-the-Dark (DID) paradigm. Active drugs were studied further using the dose–response relationship. Methods Adult female and male C57BL/6J mice were singly housed and the DID paradigm was performed using 20% EtOH over a 4-day period. Mice were administered a tetracycline or its vehicle 20 hours prior to drinking. Water and EtOH consumption was measured daily. Body weight was measured at the start of drug injections and after the final day of the experiment. Blood was collected for EtOH content measurement immediately following the final bout of drinking. Results Seven tetracyclines were tested at a 50 mg/kg dose. Only minocycline and tigecycline significantly reduced EtOH drinking, and doxycycline showed a strong effect size trend toward reduced drinking. Subsequent studies with these 3 drugs revealed a dose-dependent decrease in EtOH consumption for both female and male mice, with sex differences in efficacy. Minocycline and doxycycline reduced water intake at higher doses, although to a lesser degree than their effects on EtOH drinking. Tigecycline did not negatively affect water intake. The rank order of potency for reduction in EtOH consumption was minocycline > doxycycline > tigecycline, indicating efficacy was not strictly related to their partition coefficients or distribution constants. Conclusions Due to its effectiveness in reducing high EtOH consumption coupled without an effect on water intake, tigecycline was found to be the most promising lead tetracycline compound for further study toward the development of a new pharmacotherapy for the treatment of AUD.

Background Physicians have long reported that patients with chronic pain show higher tendencies for alcohol use disorder (AUD), and AUD patients appear to have higher pain sensitivities. The goal of this study was to test 2 hypotheses: (i) binge alcohol consumption increases inflammatory pain and mechanical and cold sensitivities; and (ii) tigecycline is an effective treatment for alcohol-mediated-increased pain behaviors and sensitivities. Both female and male mice were used to test the additional hypothesis that important sex differences in the ethanol (EtOH)-related traits would be seen. Methods “Drinking in the Dark” (DID) alcohol consuming and nondrinking control, female and male, adult C57BL/6J mice were evaluated for inflammatory pain behaviors and for the presence of mechanical and cold sensitivities. Inflammatory pain was produced by intraplantar injection of formalin (10 μl, 2.5% in saline). For cold sensation, a 20 μl acetone drop was used. Mechanical withdrawal threshold was measured by an electronic von Frey anesthesiometer. Efficacy of tigecycline (80 mg/kg i.p.) to reduce DID-related pain responses and sensitivity was tested. Results DID EtOH consumption increased inflammatory pain behavior, while it also produced sustained mechanical and cold sensitivities in both females and males. Tigecycline produced antinociceptive effects in males; a pro-nociceptive effect was seen in females in the formalin test. Likewise, the drug reduced both mechanical and cold sensitivities in males, but females showed an increase in sensitivity in both tests. Conclusions Our results demonstrated that binge drinking increases pain, touch, and thermal sensations in both sexes. In addition, we have identified sex-specific effects of tigecycline on inflammatory pain, as well as mechanical and cold sensitivities. The development of tigecycline as an AUD pharmacotherapy may need consideration of its pro-nociceptive action in females. Further studies are needed to investigate the mechanism underlying the sex-specific differences in nociception.

Background Alcohol use disorder (AUD) is a spectrum disorder characterized by mild to severe symptoms, including potential withdrawal signs upon cessation of consumption. Approximately five hundred thousand patients with AUD undergo clinically relevant episodes of withdrawal annually (New Engl J Med, 2003, 348, 1786). Recent evidence indicates potential for drugs that alter neuroimmune pathways as new AUD therapies. We have previously shown the immunomodulatory drugs, minocycline and tigecycline, were effective in reducing ethanol (EtOH) consumption in both the 2-bottle choice and drinking-in-the-dark paradigms. Here, we test the hypothesis that tigecycline, a tetracycline derivative, will reduce the severity of EtOH withdrawal symptoms in a common acute model of alcohol withdrawal (AWD) using a single anesthetic dose of EtOH in seizure sensitive DBA/2J (DBA) mice. Methods Naive adult female and male DBA mice were given separate injections of 4 g/kg i.p. EtOH with vehicle or tigecycline (0, 20, 40, or 80 mg/kg i.p.). The 80 mg/kg dose was tested at 3 time points (0, 4, and 7 hours) post EtOH treatment. Handling-induced convulsions (HICs) were measured before and then over 12 hours following EtOH injection. HIC scores and areas under the curve were tabulated. In separate mice, blood EtOH concentrations (BECs) were measured at 2, 4, and 7 hours postinjection of 4 g/kg i.p. EtOH in mice treated with 0 and 80 mg/kg i.p. tigecycline. Results AWD symptom onset, peak magnitude, and overall HIC severity were reduced by tigecycline drug treatment compared to controls. Tigecycline treatment was effective regardless of timing throughout AWD, with earlier treatment showing greater efficacy. Tigecycline showed a dose-responsive reduction in acute AWD convulsions, with no sex differences in efficacy. Importantly, tigecycline did not affect BECs over a time course of elimination. Conclusions Tigecycline effectively reduced AWD symptoms in DBA mice at all times and dosages tested, making it a promising lead compound for development of a novel pharmacotherapy for AWD. Further studies are needed to determine the mechanism of tigecycline action.

Successful hydrologic modeling depends heavily on high-quality rainfall data sets. If hydrologists cannot determine what is coming into a watershed, there is little chance that any hydrologic model will accurately estimate what is coming out on a consistent basis. Hydrologists are frequently forced to use rainfall data sets derived from sparse rain gauge networks that poorly resolve critical rainfall features, leading to inadequate model results. Over the past several years, the modernizing National Weather Service, the Federal Aviation Administration, and the Department of Defense have installed a new nationwide network of weather radars, providing a rich suite of real-time meteorological observations. Radar rainfall estimates from the new radars cover vast areas at a spatial and temporal resolution that would be impossibly expensive to match with a conventional rain gauge network. Hydrologists can now literally see between the gauges and view truer representations of the spatial distribution of rainfall than ever before. Results from the analysis of the January 9-10, 1995, storms in Sacramento, California, show that gauge-adjusted radar rainfall estimates help resolve rainfall features that could not have been inferred from rain gauge analysis alone. Accurate estimates of the volume, timing, and distribution of rainfall helped create excellent modeling results. In Waco, Texas, radar rainfall estimates were used to improve the analysis of excess inflow and infiltration into city storm sewers. The radar rainfall analyses enabled modelers to account for inflow/infiltration variations down to the neighborhood level.

Current processes for developing Depth Area Reduction Factors (DARF), design storms, and temporal rainfall distributions from approximately 20 agencies as well procedures identified in US National Oceanic and Atmospheric Administration (NOAA) rainfall atlases were reviewed and benchmarked for the Contra Costa County Flood Control and Water Conservation District (District) in Martinez, CA. The majority of the agency procedures reviewed uses some variation of the NOAA Atlas DARF curves. Modified NOAA Atlas 2 procedures often follow the longer DARF duration (e.g. 3-hr – 24-hr) storms of NOAA Atlas 2 but use NOAA processes to create new DARFs for short durations (e.g. 5-min to 1-hr). Two agencies, the City of Colorado Springs and the Metropolitan Sewer District of St. Louis are utilizing the growing database of radar rainfall estimates to develop DARF curves using a storm-centered approach. Most of the counties evaluated in this study rely on a Rational Method approach for small drainage areas which requires an estimate of rainfall intensity. Each county or agency has a unique method for obtaining the rainfall intensity, but the differences between them appear minor. Only three of the counties or agencies reviewed have design storm procedures with additional steps to adjusting point rainfall estimates beyond applying a DARF factor. Typically, one of three general approaches is used in determining the temporal distribution of a design storm. The first is called a nested or balanced storm pattern. The second approach is the use of synthetic curves such as SCS types I, IA, II and III. The third approach is the use of local historical data to develop a temporal distribution.

As part of the development of radar-based design storms in the Phoenix, AZ, area used for water infrastructure design, an analysis of expected antecedent moisture conditions was needed to support hydrologic/hydraulic modeling. Several hundred precipitation gages found in Phoenix from 1994 to 2012 were identified and evaluated to find the ideal antecedent precipitation for a design storm. When using a design storm of a given frequency for infrastructure planning, some assumption must be made regarding the moisture conditions likely present at the beginning of the storm. If a moisture condition is assumed that is relatively rare, the combined probabilities (i.e. event probability and antecedent moisture probability) can be quite different than the intended design frequency. The task reported herein used antecedent precipitation in the Phoenix area as a surrogate for antecedent moisture conditions. The study evaluated the likelihood of antecedent precipitation impacting the design storm response and found that dry antecedent moisture conditions can safely be assumed and are recommended for the a design storm.

Two catastrophic floods in the Chehalis River Basin in west central Washington in the past decade prompted several initiatives to manage flood risk in the basin. One initiative was the development of a comprehensive flood warning system to improve emergency response to developing flood threats and to improve the operating environment for future dams and or levees in the basin. After a needs analysis canvassing stakeholders with interests in the basin, a flood warning system was implemented that included an expanded rain, temperature, and stream gage network, an internet based data collection, management and distribution system, as well as inundation mapping for approximately 100 miles of stream channel. The system leveraged existing automated gage networks in the region, an internet based data management service, and National Weather Service river forecasts to form the core of the system. The web site features total public access to observed hydrometeorological data, weather forecasts, quantitative precipitation and temperature forecasts, local road conditions as well as links to other critical flood preparedness resources. A sophisticated alarm manager is included that enables automatic message transmission via email or text messaging to mobile devices when user specified alarm criteria are met. Neighborhood level inundation mapping keyed to the full range of National Weather Service river forecasts covering initial monitoring stages through minor, moderate and major flooding is included. Residents can clearly see where and when flooding will occur relative to homes, critical facilities, and avenues of ingress and egress in advance of anticipated flooding. The Chehalis River Basin flood warning system will be described and summarized. In addition, it will be shown how the system is easily scalable to statewide application.

[1] This paper presents a weather generator that allows simulation of hydrometeorological variables representative of a given geographic location: precipitation, total cloud cover, incoming shortwave radiation, air temperature, humidity, and wind speed. The approach captures the essential relationships among the quantities of interest, while modeling the diurnal variation of weather conditions at the hourly scale. Precipitation is considered to be the key driver of simulated hydrometeorological conditions, which leads to a consistent covariation of the weather variables. The generator was calibrated and validated with data from three meteorological stations located in New Mexico, Arizona, and Oklahoma. The set of variables reproduced by the weather generator can serve as input to a number of models of environmental systems, involving hydrological, ecological, water resources, and agricultural applications. The model is also suitable for creating scenarios of climate regimes (e.g., dry versus wet climates) useful in sensitivity studies. The source codes of the weather generator, manual, and test applications are publicly available.

Traditional analyses defining the spatial structure of design storms are interpreted from point rain gage data. However, rarely are rain gage networks dense enough to provide accurate assessments of the very storms these networks are intended to monitor. Furthermore, rainfall topologies interpolated from point data may be quite different from the actual storm shapes. For the past decade, large scale databases of radar rainfall estimates have been created and archived providing a rich store of info rmation that has never existed before. The se databases can be mined for detailed information regarding the spatial characteristics of storms. This paper will present findings on the spatial structure of storms from Florida and other locations in the United States. Example frequency distribution s of storm parameters will be presented. In addition, information will be presented on how th ese data are being used to develop more realistic design storms.

Rainfall distributions from rain gages are typically estimated by assuming a spatial geometry tied to point rain gage observations using, for example, Thiessen polygons, inverse distance squared weighting, or statistical Kriging techniques. Unfortunately, the spatial distributions inferred by these approaches have little connection with how rain actually falls. Since the release of the WSR-88D (NEXRAD) radar in the early 1990s, many hydrologists and engineers have begun using gage-adjusted radar rainfall estimates for hydrologic and water resource modeling. Over large areas under multiple NEXRAD radar coverages, the quality of radar rainfall estimates can vary significantly from one location to another. Visible discontinuities can develop at the limits of coverage of a single NEXRAD site because of slightly different performance or calibration techniques used at the different radar sites. Using a variety of GIS procedures for this study, these discontinuities were eliminated and locations of ground clutter were suppressed, yielding a seamless map of unadjusted radar rainfall estimates. These data were adjusted with over 400 rain gages located throughout the state using a modified spatial adjustment technique originally developed by Brandes at the National Severe Storms Lab in the mid-1970s. This approach was able to retain the volumetric rainfall estimates from the gages while maintaining the spatial signature of the rainfall. Use of this technique greatly improves gage-adjusted radar rainfall estimates.

An active 1999 hurricane season brought several significant hurricanes, tropical storms, and other heavy rainfall events to the Florida Peninsula. During this period, high-resolution gageadjusted radar-rainfall estimates were developed for the entire state. Radar-rainfall estimates from a mosaic of overlapping radar coverages in Florida were combined with local rain gages from northeastern Florida to create a composite data set of gage-adjusted radar-rainfall estimates on a 2 km x 2 km grid every 15 minutes. This paper presents comparisons between gage measurements and the resulting radar estimates. The results will focus on a 12,400 square mile area in northeastern Florida containing 97 rain gages. The results are quite promising. For example, the R-squared correlation coefficient for storm totals (gage & gage-adjusted radar) from Hurricane Floyd was 0.87. Example gage-radar scatter grams, gage-radar rainfall accumulation charts, and maps will be presented. Perhaps the most important result from radar-rainfall estimates is the improvement in the spatial definition of rainfall when compared to the spatial definitions derived from rain gages alone. Conventional techniques for distributing rainfall such as inverse distance-squared, Kriging, or Thiessen polygons often severely distort our understanding of the true rainfall distribution. Conventional techniques are also geometrically static and fail to convey storm dynamics to hydrologic models. High resolution radar-rainfall estimates not only provide a better definition of the volumetric distribution of rainfall at each time step, the high resolution data also better communicates storm dynamics to hydrologic models, which leads to more consistent model results.

In addition to increased flood runoff, urban development has caused a significant increase in sediment loads in streams. While many means of sediment and runoff control have been proposed, stormwater detention has been shown to be one of the more cost efficient means. Because detention facilities have not been used extensively in the past, a data base is not available for determining the effect of design factors on sediment trap efficiency and runoff control characteristics. A mathematical model, which includes erosion, sedimentation, and detention facility components, was developed from principles of hydraulics and classical settling mechanics. The model was used to examine the effect of: (1)Detention basin location; (2)soil particle size distribution; (3)basin depth; (4)initial storage, and (5)orifice diameter. An understanding of the relative importance of these factors may lead to better design of stormwater detention facilities.

To establish optimum land-use policies, it is important that local planners understand the economic implications of various land-use alternatives. Data were collected for two alternative forms of residential housing, single-family detached homes and apartment complexes in Frederick County, Maryland. A benefit-cost analysis was performed to determine the relative profitability of these housing forms in Frederick County. The results compared favorably to a similar study conducted in Anne Arundel County, Maryland. Additionally, sensitivity analyses were performed to determine the relative importance of factors affecting the benefit-cost ratio. These factors included (1) The property tax assessment rate; (2) the average household income; (3) the average number of school children per dwelling; and (4) the average number of inhabitants per dwelling.