Informing Future Risks of Record-Level Rainfall in the United States.

The changing risk of extreme precipitation is difficult to project. Events are rare by definition, and return periods of heavy precipitation events are often calculated assuming a stationary climate. Furthermore, ensembles of climate model projections are not large enough to fully categorize the tails of the distribution. To address this, we cluster the contiguous United States into self-similar hydroclimates to estimate changes in the expected frequency of extremely rare events under scenarios of global mean temperature change. We find that, although there is some regional variation, record events are projected in general to become more intense, with 500-year events intensifying by 10-50% under 2 °C of warming and by 40-100% under 4 °C of warming. This analysis could provide information to inform regional prioritization of resources to improve the resilience of U.S. infrastructure.

Characterization of pathogenesis of and immune response to Burkholderia pseudomallei K96243 using both inhalational and intraperitoneal infection models in BALB/c and C57BL/6 mice.

Burkholderia pseudomallei, the etiologic agent of melioidosis, is a Gram negative bacterium designated as a Tier 1 threat. This bacterium is known to be endemic in Southeast Asia and Northern Australia and can infect humans and animals by several routes. Inhalational melioidosis has been associated with monsoonal rains in endemic areas and is also a significant concern in the biodefense community. There are currently no effective vaccines for B. pseudomallei and antibiotic treatment can be hampered by non-specific symptomology and also the high rate of naturally occurring antibiotic resistant strains. Well-characterized animal models will be essential when selecting novel medical countermeasures for evaluation prior to human clinical trials. Here, we further characterize differences between the responses of BALB/c and C57BL/6 mice when challenged with low doses of a low-passage and well-defined stock of B. pseudomallei K96243 via either intraperitoneal or aerosol routes of exposure. Before challenge, mice were implanted with a transponder to collect body temperature readings, and daily body weights were also recorded. Mice were euthanized on select days for pathological analyses and determination of the bacterial burden in selected tissues (blood, lungs, liver, and spleen). Additionally, spleen homogenate and sera samples were analyzed to better characterize the host immune response after infection with aerosolized bacteria. These clinical, pathological, and immunological data highlighted and confirmed important similarities and differences between these murine models and exposure routes.

Query2Question: Translating Visualization Interaction into Natural Language.

Richly interactive visualization tools are increasingly popular for data exploration and analysis in a wide variety of domains. Existing systems and techniques for recording provenance of interaction focus either on comprehensive automated recording of low-level interaction events or on idiosyncratic manual transcription of high-level analysis activities. In this paper, we present the architecture and translation design of a query-to-question (Q2Q) system that automatically records user interactions and presents them semantically using natural language (written English). Q2Q takes advantage of domain knowledge and uses natural language generation (NLG) techniques to translate and transcribe a progression of interactive visualization states into a visual log of styled text that complements and effectively extends the functionality of visualization tools. We present Q2Q as a means to support a cross-examination process in which questions rather than interactions are the focus of analytic reasoning and action. We describe the architecture and implementation of the Q2Q system, discuss key design factors and variations that effect question generation, and present several visualizations that incorporate Q2Q for analysis in a variety of knowledge domains.

Visual analysis of higher-order conjunctive relationships in multidimensional data using a hypergraph query system.

Visual exploration and analysis of multidimensional data becomes increasingly difficult with increasing dimensionality. We want to understand the relationships between dimensions of data, but lack flexible techniques for exploration beyond low-order relationships. Current visual techniques for multidimensional data analysis focus on binary conjunctive relationships between dimensions. Recent techniques, such as cross-filtering on an attribute relationship graph, facilitate the exploration of some higher-order conjunctive relationships, but require a great deal of care and precision to do so effectively. This paper provides a detailed analysis of the expressive power of existing visual querying systems and describes a more flexible approach in which users can explore n-ary conjunctive inter- and intra- dimensional relationships by interactively constructing queries as visual hypergraphs. In a hypergraph query, nodes represent subsets of values and hyperedges represent conjunctive relationships. Analysts can dynamically build and modify the query using sequences of simple interactions. The hypergraph serves not only as a query specification, but also as a compact visual representation of the interactive state. Using examples from several domains, focusing on the digital humanities, we describe the design considerations for developing the querying system and incorporating it into visual analysis tools. We analyze query expressiveness with regard to the kinds of questions it can and cannot pose, and describe how it simultaneously expands the expressiveness of and is complemented by cross-filtering.

Variation in estimated ozone-related health impacts of climate change due to modeling choices and assumptions.

BACKGROUND: Future climate change may cause air quality degradation via climate-induced changes in meteorology, atmospheric chemistry, and emissions into the air. Few studies have explicitly modeled the potential relationships between climate change, air quality, and human health, and fewer still have investigated the sensitivity of estimates to the underlying modeling choices. OBJECTIVES: Our goal was to assess the sensitivity of estimated ozone-related human health impacts of climate change to key modeling choices. METHODS: Our analysis included seven modeling systems in which a climate change model is linked to an air quality model, five population projections, and multiple concentration-response functions. Using the U.S. Environmental Protection Agency's (EPA's) Environmental Benefits Mapping and Analysis Program (BenMAP), we estimated future ozone (O(3))-related health effects in the United States attributable to simulated climate change between the years 2000 and approximately 2050, given each combination of modeling choices. Health effects and concentration-response functions were chosen to match those used in the U.S. EPA's 2008 Regulatory Impact Analysis of the National Ambient Air Quality Standards for O(3). RESULTS: Different combinations of methodological choices produced a range of estimates of national O(3)-related mortality from roughly 600 deaths avoided as a result of climate change to 2,500 deaths attributable to climate change (although the large majority produced increases in mortality). The choice of the climate change and the air quality model reflected the greatest source of uncertainty, with the other modeling choices having lesser but still substantial effects. CONCLUSIONS: Our results highlight the need to use an ensemble approach, instead of relying on any one set of modeling choices, to assess the potential risks associated with O(3)-related human health effects resulting from climate change.

Cross-filtered views for multidimensional visual analysis.

Analysis of multidimensional data often requires careful examination of relationships across dimensions. Coordinated multiple view approaches have become commonplace in visual analysis tools because they directly support expression of complex multidimensional queries using simple interactions. However, generating such tools remains difficult because of the need to map domain-specific data structures and semantics into the idiosyncratic combinations of interdependent data and visual abstractions needed to reveal particular patterns and distributions in cross-dimensional relationships. This paper describes: 1) a method for interactively expressing sequences of multidimensional set queries by cross-filtering data values across pairs of views and 2) design strategies for constructing coordinated multiple view interfaces for cross-filtered visual analysis of multidimensional data sets. Using examples of cross-filtered visualizations of data from several different domains, we describe how cross-filtering can be modularized and reused across designs, flexibly customized with respect to data types across multiple dimensions, and incorporated into more wide-ranging multiple view designs. We also identify several important limitations of the approach. The demonstrated analytic utility of these examples suggests that cross-filtering is a suitable design pattern for instantiation in a wide variety of visual analysis tools.

Conjunctive visual forms.

Visual exploration of multidimensional data is a process of isolating and extracting relationships within and between dimensions. Coordinated multiple view approaches are particularly effective for visual exploration because they support precise expression of heterogeneous multidimensional queries using simple interactions. Recent visual analytics research has made significant progress in identifying and understanding patterns of composed views and coordinations that support fast, flexible, and open-ended data exploration. What is missing is formalization of the space of expressible queries in terms of visual representation and interaction. This paper introduces the Conjunctive Visual Form model in which visual exploration consists of interactively-driven sequences of transitions between visual states that correspond to conjunctive normal forms in boolean logic. The model predicts several new and useful ways to extend the space of rapidly expressible queries through addition of simple interactive capabilities to existing compositional patterns. Two recent related visual tools offer a subset of these capabilities, providing a basis for conjecturing about such extensions.

Evaluation and comparison of portable emissions measurement systems and federal reference methods for emissions from a back-up generator and a diesel truck operated on a chassis dynamometer.

There is considerable interest in portable emissions measurement systems (PEMS) for emission inventory and regulatory applications. For this study, four commercial PEMS were compared with a Federal Reference Method (FRM) for measuring emissions from a back-up generator (BUG) over steady-state loads and a diesel truck on transient and steady-state chassis dynamometer tests. The agreement between the PEMS and the FRM varied depending on the pollutant and the particular PEMS tested for both the BUG and chassis dynamometer testing. The best performing PEMS for both the BUG and chassis testing was within approximately 12% for NOx of the FRM. For the BUG testing, several PEMS showed agreement with the FRM within approximately 5% for CO2. For the chassis dynamometer testing, the best PEMS showed agreement typically within approximately 5% for CO2. PM measurements for the BUG testing were low compared to the FRM, with the best measurements approximately 20% lower. For the chassis testing, two PM PEMS showed a good correlation but a high bias, while the correlation was worse for the other two PEMS. For each emissions component, some PEMS under different test conditions showed considerably larger deviations than those for the best performing PEMS.

Self-reported adherence versus pill count in Parkinson's disease: the NET-PD experience.

PURPOSE: To compare the Morisky medication adherence questionnaire to pill counts as measures of adherence in the NET-PD futility clinical trials. BACKGROUND: Like in other chronic diseases, non-adherence with medications occurs in Parkinson's disease (PD), although nonadherence has not been of significant concern in most PD clinical trials. The most common approach to assessment is to do a pill count at each visit. The simple, 4-question Morisky medication adherence questionnaire may provide an alternative approach to monitoring treatment adherence in PD. METHODS: Adherence data from two NET-PD Phase II clinical trials enrolling a total of 413 participants were analyzed. The association between demographic and clinical characteristics and adherence was explored. RESULTS: Ninety-percent of participants took 80% or more of the study drug. However, the Morisky medication adherence questionnaires showed 56% report high and 44% report medium adherence. Agreement between the two measures is fair (ICC = 0.40). CONCLUSIONS: Overall adherence as assessed by pill count appears high. The Morisky medication adherence questionnaire may be useful in PD clinical trials, since it is moderately correlated to pill count and may be more sensitive to nonadherence.

Evaluation of a new pulse oximeter sensor.

BACKGROUND: A new forehead noninvasive oxygen saturation sensor may improve signal quality in patients with low cardiac index. OBJECTIVES: To examine agreement between oxygen saturation values obtained by using digit-based and forehead pulse oximeters with arterial oxygen saturation in patients with low cardiac index. METHODS: A method-comparison study was used to examine the agreement between 2 different pulse oximeters and arterial oxygen saturation in patients with low cardiac index. Readings were obtained from a finger and a forehead sensor and by analysis of a blood sample. Bias, precision, and root mean square differences were calculated for the digit and forehead sensors. Differences in bias and precision between the 2 noninvasive devices were evaluated with a t test (level of significance P<.05). RESULTS: Nineteen patients with low cardiac index (calculated as cardiac output in liters per minute divided by body surface area in square meters; mean 1.98, SD 0.34) were studied for a total of 54 sampling periods. Mean (SD) oxygen saturations were 97% (2.4) for blood samples, 96% (3.2) for the finger sensor, and 97% (2.8) for the forehead sensor. By Bland Altman analysis, bias +/- precision was -1.16 +/- 1.62% for the digit sensor and -0.36 +/- 1.74% for the forehead sensor; root mean square differences were 1.93% and 1.70%, respectively. Bias and precision differed significantly between the 2 devices; the forehead sensor differed less from the blood sample. CONCLUSIONS: In patients with low cardiac index, the forehead sensor was better than the digit sensor for pulse oximetry.

Effect of aspirin, clopidogrel and dipyridamole on soluble markers of vascular function in normal volunteers and patients with prior ischaemic stroke.

Although the mechanisms of action by which aspirin, clopidogrel and dipyridamole inhibit platelets are well characterised, their effects on soluble modulators of thrombosis, inflammation, and endothelial function have yet to assessed systematically. In this investigation aspirin (A), clopidogrel (C), and dipyridamole (D) were administered singly and in combination (A, C, D, AC, AD, CD, ACD) in random order for 2 weeks (without washout) to 11 healthy subjects and 11 patients with previous ischaemic stroke. At the end of each treatment period plasma cyclic guanosine monophosphate (cGMP), monocyte chemoattractant pertide-1 (MCP-1), nitric oxide metabolites (NO(x)), plasminogen activator inhibitor-1 (PAI-1) and von Willebrand factor (vWf); and serum C-reactive protein (CRP) and platelet derived growth factor (PDGF); were measured blinded to treatment. Dipyridamole reduced plasma vWf levels (%) in both volunteers, -10.0 (4.95), and patients, -10.11 (4.34) (p < 0.05). Dipyridamole also lowered CRP (mg/l) in patients, -0.96 (0.47), but not volunteers. Clopidogrel reduced PAI-1 (ng/ml) in volunteers, -5.30 (2.20) (p < 0.05), and patients, -3.61 (2.75) (non-significant trend). Aspirin lowered PDGF (ng/ml) in volunteers, -3.46 (1.55), but not patients. Triple antiplatelet therapy was superior to dual and mono therapy in reducing vWf levels. In conclusion, antiplatelet agents have non-platelet-related effects on soluble modulators of thrombosis, inflammation, and endothelial function. In particular, dipyridamole reduces plasma vWf and clopidogrel lowers plasma PAI-1 levels. These effects may explain, in part, their roles in preventing atherothrombogenesis.

Effects of aspirin, clopidogrel and dipyridamole administered singly and in combination on platelet and leucocyte function in normal volunteers and patients with prior ischaemic stroke.

The aim of this study was to assess whether triple antiplatelet therapy is superior to dual and mono therapy in attenuating platelet and leucocyte function. Aspirin (A), clopidogrel (C), and dipyridamole (D) were administered singly and in various combinations (A, C, D, AC, AD, CD, ACD), each for two weeks (without washout) to 11 healthy subjects and to 11 patients with previous ischaemic stroke in two randomised multiway crossover trials. At the end of each two-week period platelet aggregation, platelet-leucocyte conjugate formation and leucocyte activation were measured ex vivo blinded to treatment. Platelets were stimulated with collagen; additional measurements were made with adenosine diphosphate (ADP), platelet activating factor (PAF), adrenaline and the combination of, ADP, PAF and adrenaline. Results show that in the presence of collagen, ACD was superior to all antagonists or combinations, except AC, in reducing aggregation, platelet-leucocyte conjugate formation, and monocyte activation (all p<0.05). ACD was also more potent than other treatments, except AC, in inhibiting the aggregation and platelet-monocyte conjugate formation induced by the combination of ADP, PAF and adrenaline. The effects were similar in both volunteers and stroke patients. No serious adverse events or major bleeding events occurred. Triple antiplatelet therapy did not appear to be more effective than combined aspirin and clopidogrel in moderating platelet and leucocyte function. Any additional clinical benefit provided by dipyridamole may be through other mechanisms of action.

Sample size calculations in acute stroke trials: a systematic review of their reporting, characteristics, and relationship with outcome.

BACKGROUND AND PURPOSE: Only a few randomized controlled trials in acute stroke have shown a treatment-related benefit. Inadequate trial design, especially low sample size, may partly explain this failure. We investigated sample size calculations (SSCs) in a systematic review of acute stroke trials. METHODS: Full reports of nonconfounded randomized controlled trials that recruited patients within 1 week of stroke onset and were published before the end of 2001 were identified from the Cochrane Library and other bibliographic databases. Information on the SSC and outcome event rates was collected for each trial. RESULTS: Of 189 identified trial reports, 57 (30%) reported > or =1 components of the SSC, phase II 14/129 (11%) versus phase III 43/60 (72%) (P<0.001), with 32 (56%) giving all the required parameters. Significance (alpha) was mentioned in 54 (96%) reports; 53 used a significance level of alpha=0.05. And 55 (98%) reports gave the power (1-beta) of the study (median [25th and 75th percentile] 0.80 [0.80, 0.90]). The anticipated percentage of control subjects having a primary outcome event was given in 24 (42%) articles: case fatality 21.8% (11.8%, 23.5%, n=4) and combined death or disability/dependency 55.5% (44.5%, 66.3%, n=20); 25 studies used other outcomes and 8 studies gave insufficient information. Four of the 22 trials achieved a control rate within 5% of their prediction. 49 (86%) reports gave the anticipated treatment effect; case fatality: anticipated 9.5% (1.1%, 12.5%, n=6), achieved -0.3% (-4.1%, +2.4%); combined death or disability/dependency: anticipated 13.0% (10.0%, 16.0%, n=25), achieved 1.8% (-0.5%, +5.4%). The median calculated sample size was 600 (198, 995, n=54). CONCLUSIONS: Too few trial publications report the assumptions underlying their SSC. Most trials were underpowered, ie, power <0.90, used inappropriate assumptions for event rates, and were grossly overoptimistic in their expectation of treatment effect. These deficiencies will together have resulted in trials being far too small and reduced their chance of being able to detect real treatment effects.

The effects of transdermal glyceryl trinitrate, a nitric oxide donor, on blood pressure, cerebral and cardiac hemodynamics, and plasma nitric oxide levels in acute stroke.

High blood pressure in acute stroke is common and appears to be associated with a poor outcome. Lowering blood pressure might therefore improve outcome, provided that cerebral perfusion is not compromised. We assessed the effects of glyceryl trinitrate (GTN) on cerebral and systemic hemodynamic measures in acute stroke. Ninety patients with acute ischemic or hemorrhagic stroke were randomized within 72 hours of ictus to transdermal GTN given daily for 10 days (either 5 mg, 5 mg for 4 days then 10 mg, or 10 mg) or control. Twenty-four hour blood pressure monitoring, middle cerebral artery blood velocity, cardiac output, augmentation index, and plasma nitric oxide levels were each measured at baseline and then on days 1, 4, 5, and 10. The primary outcome was blood pressure on day 1. We found that GTN lowered mean peripheral arterial blood pressure on day 1 by 5.3% to 6.7% in a dose dependent manner as compared with control (mean, SD): control, 108.8 (15.1) mmHg; 5 mg, 102.5 (13.9) mmHg; 5/10 mg, 103.4 (14.9) mmHg; 10 mg, 101.5 (12.6) mmHg; (P = .005). Increasing the dose from 5 to 10 mg on day 5 resulted in an overall reduction in blood pressure of 11.4% as compared with leaving the dose at 5 mg (P = .006). GTN reduced peripheral pulse pressure, central aortic blood pressure, pulse pressure, and augmentation index on day 1. Middle cerebral artery blood velocity and pulsatility index in the affected hemisphere, cardiac output, systemic peripheral resistance, and plasma nitric oxide levels were not altered by GTN. Treatment with GTN was associated with headache: control 0 (0%), GTN 9 (15%) (P = .027); no negative effect on end-of-treatment death or deterioration, or 3 month death or dependency was discernable. GTN reduced peripheral blood pressure in a dose-dependent fashion in patients with acute stroke at day 1 and also reduced central blood pressure and augmentation index. In contrast, GTN did not alter middle cerebral artery blood velocity or pulsatility index in the affected hemispheres, suggesting that cerebral blood flow did not change. A trial assessing the effect of lowering blood pressure with GTN on safety and functional outcome in patients with acute stroke is now warranted.