Search

Summary Background INCREASE was a randomised, placebo-controlled, phase 3 trial that evaluated inhaled treprostinil in patients with interstitial lung disease (ILD) and associated pulmonary hypertension. Treprostinil improved exercise capacity from baseline to week 16, assessed with the use of a 6-min walk test, compared with placebo. Improvements in forced vital capacity (FVC) were also reported. The aim of this post-hoc analysis was to further characterise the effects of inhaled treprostinil on FVC in the overall study population and in various subgroups of interest. Methods In this post-hoc analysis, we evaluated FVC changes in the overall study population and in various subgroups defined by cause of disease or baseline clinical parameters. The study population included patients aged 18 years and older who had a diagnosis of ILD based on evidence of diffuse parenchymal lung disease on chest CT done within 6 months before random assignment (not centrally adjudicated). All analyses were done on the intention-to-treat population, defined as individuals who were randomly assigned and received at least one dose of study drug. The INCREASE study is registered with ClinicalTrials.gov, NCT02630316. Findings Between Feb 3, 2017, and Aug 30, 2019, 326 patients were enrolled in the INCREASE trial. Inhaled treprostinil was associated with a placebo-corrected least squares mean improvement in FVC of 28·5 mL (SE 30·1; 95% CI −30·8 to 87·7; p=0·35) at week 8 and 44·4 mL (35·4; −25·2 to 114·0; p=0·21) at week 16, with associated percentage of predicted FVC improvements of 1·8% (0·7; 0·4 to 3·2; p=0·014) and 1·8% (0·8; 0·2 to 3·4; p=0·028). Subgroup analysis of patients with idiopathic interstitial pneumonia showed FVC differences of 46·5 mL (SE 39·9; 95% CI −32·5 to 125·5; p=0·25) at week 8 and 108·2 mL (46·9; 15·3 to 201·1; p=0·023) at week 16. Analysis of patients with idiopathic pulmonary fibrosis showed FVC differences of 84·5 mL (52·7; −20·4 to 189·5; p=0·11) at week 8 and 168·5 mL (64·5; 40·1 to 297·0; p=0·011) at week 16. The most frequent adverse events included cough, headache, dyspnoea, dizziness, nausea, fatigue, and diarrhoea. Interpretation In patients with ILD and associated pulmonary hypertension, inhaled treprostinil was associated with improvements in FVC versus placebo at 16 weeks. This difference was most evident in patients with idiopathic interstitial pneumonia, particularly idiopathic pulmonary fibrosis. Inhaled treprostinil appears to be a promising therapy for idiopathic pulmonary fibrosis that warrants further investigation in a prospective, randomised, placebo-controlled study. Funding United Therapeutics Corporation.

Treprostinil is a prostacyclin approved for the treatment of pulmonary arterial hypertension. Commercial data sets indicate that approximately 20–25% of patients are prescribed a higher dose than the maximum recommended dosage of nine breaths per treatment session (bps) (54 μg), four times a day (QID) and numerous studies have demonstrated the safety of doses >9 bps QID. This phase 4, retrospective analysis of specialty pharmacy records assessed the effects of inhaled treprostinil at doses >9 bps QID. Patients receiving inhaled treprostinil between September 2009 and June 2018 were included, and a random sampling of 5000 patients was selected for further analysis. Subjects were grouped based on the highest dose reached for ≥2 months within a rolling six-month window and were followed for up to three years. Of the total of 5000 patients analyzed, 28.5% received >9 bps QID. Survival rates were significantly higher in the >9 bps QID dosing group for years one, two, and three ( P 9 bps (17.5 months) compared to doses ≤9 bps (9.5 moths; P 9 bps at years 1, 2, and 3 ( P 9 bps QID had a higher rate of survival and drug persistence over a three-year period, suggesting that higher doses may provide clinically relevant benefits while remaining tolerable.

Rationale The INCREASE study of inhaled treprostinil met its primary endpoint of change in 6-minute walk distance at Week 16. In addition, there were significantly fewer clinical worsening events in patients receiving inhaled treprostinil. However, the incidence of multiple events in the same patient is unknown. Objectives This post-hoc analysis evaluated the effect of continued treatment with inhaled treprostinil on the frequency and impact of multiple disease progression events. Methods Patients enrolled in INCREASE were analyzed for disease progression events, defined as ≥15% decline in 6-minute walk distance, exacerbation of underlying lung disease, cardiopulmonary hospitalization, lung transplantation, ≥10% decline in forced vital capacity, or death during the duration of the 16-week study. Measurements and Main Results 147 disease progression events occurred in the inhaled treprostinil group (89/163 patients, 55%) compared to 215 events (109/163 patients, 67%) in the placebo group (p=0.018). There was a lower incidence of each disease progression component in the inhaled treprostinil group: 6-minute walk distance decline (45 vs. 64 events), lung disease exacerbation (48 vs. 72 events), forced vital capacity decline (19 vs. 33), cardiopulmonary hospitalization (23 vs. 33 events) and death (10 vs. 12). Fewer patients receiving inhaled treprostinil had multiple progression events compared to placebo (35 vs. 58; 22% vs. 36%, p=0.005). Conclusions Patients who received inhaled treprostinil were significantly less likely to experience further disease progression events after an initial event compared to placebo. These results support the continuation of inhaled treprostinil despite the occurrence of disease progression in clinical practice. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background Until recently, many clinical trials in patients with pulmonary arterial hypertension (PAH) evaluated exercise capacity with 6-minute walk distance (6MWD) as the primary endpoint. Common secondary endpoints include PAH functional class (FC), which assesses symptoms, and either brain natriuretic peptide (BNP) or the inactive N-terminal cleavage product of its prohormone (NT-proBNP), which assesses cardiac function. Objective Examine the relationships among 6MWD, FC, and BNP/NT-proBNP measured at baseline or follow-up with long-term outcomes in PAH studies. Methods Relevant literature from January 1990 to April 2018 were obtained by searching PubMed, Embase, and Cochrane. Articles in English reporting on associations between 6MWD, FC, or BNP/NT-proBNP and outcomes in PAH were identified. Each endpoint was evaluated individually. Prespecified inclusion and exclusion criteria were applied at level 1 (titles/abstracts) and level 2 (full-text review). Results The database search yielded 836 unique records; 65 full-text articles were reviewed. Twenty-five studies were eligible for inclusion. Findings supported the importance of measuring PAH noninvasive endpoints in predicting long-term outcomes. Patients with shorter or decreased 6MWD, poor (III/IV) or declining FC (e.g., from II to III), or elevated or increasing BNP/NT-proBNP had a higher risk of death and costly events (e.g., hospitalization, lung transplant). FC also predicted health care resource utilization and costs. Collectively, these endpoints establish risk groups that predict likelihood of complications from PAH or death. Conclusion Assessment of 6MWD, FC, and BNP/NT-proBNP provides low-cost, efficient, and noninvasive means of predicting long-term health and economic outcomes in patients with PAH.

Electrochromic (EC) materials and devices provide a user-controlled, dynamic way of displaying information using low power, making them interesting for a range of applications in numerous markets, including logistics, retail, consumer goods, and health care. To optimize the cost while simplifying the production, expanding the color space, and enhancing the contrast and vibrancy of EC displays aimed for cost-sensitive products, we sought to reduce the number of layers as well as remove the underlying conducting layer that accounts for a substantial fraction of the cost of a printed label. Here, we show how conjugated electrochromic polymers, which are inherently semiconducting, can be used to accomplish this goal and afford printable EC displays with a flexible form factor. Using a combination of electrochemical probes, in situ spectroscopy, solid-state conductivity, and in situ conductance measurements, we have studied and compared five different EC polymers with conductivities spanning multiple orders of magnitude and colors that span most of the visible range, identifying polymers and properties that allow for switching from the colored to the clear state without an underlying conducting layer. Finally, we incorporate these EC polymers into optimized flexible devices without an underlying conductor and demonstrate that they are able to provide on-demand, reversible colored-to-clear switching on the order of seconds to minutes, with operating voltages below ±1 V, optical memories exceeding 60 min, and a shelf-life exceeding 12 months.

Background: INCREASE was a multicenter, randomized, double-blind, placebo-controlled, 16-week study that evaluated the safety and efficacy of inhaled treprostinil in patients with interstitial lung disease and associated pulmonary hypertension (PH-ILD). The study met its primary endpoint of change in peak 6-minute walk distance at Week 16. Methods: Pulmonary function testing and exacerbations of underlying lung disease were conducted as safety assessments. This current analysis assessed the effects of inhaled treprostinil on the forced vital capacity (FVC). Findings: 326 patients were randomized to inhaled treprostinil or placebo. Inhaled treprostinil was associated with placebo-corrected improvements in the FVC of 28·5 mL (95% CI -30·8-87.7, p=0·345) and 44·4 mL (95% CI -25·3-114·1, p=0·211) at Weeks 8 and 16, respectively. The associated percent predicted FVC improvements at Weeks 8 and 16 were 1·79% (95% CI 0·37-3·21, p=0·014) and 1·80% (95% CI 0·20-3·39, p=0·028), respectively. Patients with idiopathic interstitial pneumonia (IIP) demonstrated FVC improvements of 46·5 mL (n=129, 95% CI -32·55-125·5, p=0·247) and 108·2 mL (n=115, 95% CI 15·3-201·1, p=0·023) at Weeks 8 and 16, respectively. Patients with idiopathic pulmonary fibrosis (IPF) demonstrated FVC improvements of 84·5 mL (n=78, 95% CI -20·4-189·5, p=0·113) and 168·5 mL (n=70, 95% CI 40·1-297·0, p=0·011) at Weeks 8 and 16, respectively. Interpretation: In patients with PH-ILD, inhaled treprostinil resulted in improvements in FVC compared to placebo. This difference was most evident in patients with IIP and in particular, IPF. Inhaled treprostinil appears to be a promising therapy for IPF that warrants further prospective clinical study. Trial Registration: The INCREASE study (NCT02630316) is registered with ClinicalTrials.gov. Funding Statement: The INCREASE study was funded by United Therapeutics Corporation. Declaration of Interests: SDN has received research funding and consulting fees from United Therapeutics. He has received consulting fees from Boehringer-Ingelheim, Roche-Genentech and Galapagos. He is also on the speakers bureau for Boehringer-Ingelheim and Roche-Genentech. AW reports grants from United Therapeutics Corporation, during the conduct of the study. SR reports grants from United Therapeutics Corporation, during the conduct of the study; grants and personal fees from United Therapeutics, grants and personal fees from Janssen Pharmaceuticals, personal fees from Altavant Sciences, personal fees from Liquidia Technologies, Inc., personal fees from Insmed, Inc., personal fees from Bayer Pharmaceuticals, outside the submitted work. AC reports grants from United Therapeutics Corporation, during the conduct of the study. SJ reports grants from United Therapeutics Corporation, during the conduct of the study; grants and personal fees from Bayer Pharmaceuticals, grants from Bellerophon Therapeutics, grants and personal fees from Janssen Research and Development, outside the submitted work. HD reports grants from United Therapeutics Corporation during the conduct of the study; grants and personal fees from Actelion Pharmaceuticals, outside the submitted work. DZ reports grants from United Therapeutics Corporation, during the conduct of the study. SS reports grants from United Therapeutics Corporation, during the conduct of the study; personal fees and non-financial support from Bayer Pharmaceuticals, personal fees and non-financial support from United Therapeutics, personal fees and non-financial support from Actelion Pharmaceuticals, personal fees from Liquidia, personal fees from Altavant Sciences, from GSK, grants from ACCP CHEST ILD Research Grant, personal fees from Boehringer Ingelheim, outside the submitted work. CK reports grants from United Therapeutics Corporation, during the conduct of the study; personal fees from United Therapeutics, personal fees from Actelion, personal fees from Boehringer Ingelheim Pharmaceuticals, personal fees from Genentech, outside the submitted work. LMG reports grants and personal fees from United Therapeutics Corporation, during the conduct of the study; personal fees from United Therapeutics Corporation, personal fees from Janssen and Janssen Pharmaceuticals, personal fees from Bayer Pharmaceuticals, outside the submitted work. PS reports personal fees from United Therapeutics Corporation, during the conduct of the study; personal fees from United Therapeutics Corporation, outside the submitted work. ES reports personal fees from United Therapeutics Corporation, during the conduct of the study; personal fees from United Therapeutics Corporation, outside the submitted work. LDE reports personal fees from United Therapeutics Corporation, during the conduct of the study; personal fees from United Therapeutics Corporation, outside the submitted work. AN reports personal fees from United Therapeutics Corporation, during the conduct of the study; personal fees from United Therapeutics Corporation, outside the submitted work. VFT reports grants from United Therapeutics Corporation, during the conduct of the study; personal fees from United Therapeutics, outside the submitted work. Ethics Approval Statement: The study protocol was approved by the institutional review board at each participating site. The study was monitored by an independent data and safety monitoring committee and was conducted in accordance with the principles of Good Clinical Practice.

Electrochromic cells consisting of a black-to-transmissive propylenedioxythiophene/benzothiadiazole copolymer active layer and a minimally colored dioxypyrrole-based charge storage layer were constructed, and the effect of the redox capacity ratio between the two layers was evaluated. This ratio was tuned between large excesses of either the active layer or the charge storage layer (an unbalanced configuration), to cells where both films had the same redox capacity (a balanced configuration), and the effects on cell voltage, optical contrast, switching time and switching stability were assessed. The inclusion of an auxiliary reference electrode allowed us to monitor the redox behavior of both the active layer and the charge storage layer during cell operation. With this setup, we show that the redox behavior of each layer is highly dependent on the redox capacity ratio between the two films. We also demonstrate that, in principle, any electrochromic material that has a colorless state can serve as an optically inactive charge storage material if it is present in sufficient excess in an electrochromic cell. Additionally, by monitoring the redox behavior of each individual layer during cell operation, we show that performance loss in electrochromic cells during long-term stability testing is not necessarily due to an irreversible electrochemical or structural degradation of the active material or the charge storage layer. Rather we observe a drift in the oxidation state of both layers, suggesting that the losses are reversible, and could be mitigated through proper electrochemical control of the cells. The main benefit of an unbalanced configuration is the substantial lowering of the operating voltage without compromising switching time or the contrast as long as transparency of the charge storage material is maintained.

Treprostinil is a prostacyclin analogue approved for the treatment of pulmonary arterial hypertension. Apart from the inhaled formulation, there is neither a target dose nor a ceiling dose to guide clinicians using treprostinil; doses are individualized for each patient based upon tolerability and clinical improvement. Using combined data from the pivotal subcutaneous and oral treprostinil studies, we evaluated the effect of treprostinil dose on hospitalization and exercise capacity to better define the treprostinil dose–response relationship. Data from the pivotal subcutaneous and oral treprostinil studies were combined by converting oral doses to weight-based continuous doses (ng/kg/min) accounting for patient weight and bioavailability. Patients were divided into dose tertiles (lowest, middle, highest 33%) and retrospectively analyzed. Analysis 1 assessed the effect of dose on pulmonary arterial hypertension-related and all-cause hospitalizations. Analysis 2 evaluated the effects of dose on six-minute walk distance, Borg dyspnea score, and World Health Organization functional class. Results showed that, in Analysis 1, higher doses of treprostinil were associated with significantly longer times to first pulmonary arterial hypertension-related and all-cause hospitalization. In Analysis 2, there was a trend toward improvements in six-minute walk distance with higher doses. In patients with pulmonary arterial hypertension on systemic treprostinil therapy, higher doses were associated with significantly longer time to first pulmonary arterial hypertension-related and all-cause hospitalization. There was a trend toward improvements in six-minute walk distance. Collectively, these results underscore the importance of managing prostacyclin adverse events in order to achieve appropriate dose titration. Further studies are required to confirm these findings and to better characterize the dose–response relationship of treprostinil.

This chapter aims to teach general concepts and structure–property relationships that govern color and provides electrochromic switching control. It focuses on soluble and high molecular weight electrochromic polymers. The chapter draws on systems that can switch between a colored and a clear state as these require color tuning both in the neutral and charged state. It demonstrates how to expand the range of accessible colors, as well as how switching to a more colorless oxidized state can be achieved. Electrochromism refers to the ability of a material to reversibly change its electromagnetic spectrum when undergoing a redox process. While the determination of optical contrast is a relatively straightforward measurement that can be done using a simple spectrophotometer, quantitative comparisons between materials in the literature is not trivial. The switching time is highly dependent on experimental parameters such as electrolyte concentration, cell geometry, film thickness, and substrate resistance.

Pulmonary arterial hypertension (PAH) is a chronic and progressive disorder characterized by vascular remodeling of the small pulmonary arteries, resulting in elevated pulmonary vascular resistance and ultimately, right ventricular failure. Expanded understanding of PAH pathophysiology as it pertains to the nitric oxide (NO), prostacyclin (prostaglandin I2) (PGI2) and endothelin-1 pathways has led to recent advancements in targeted drug development and substantial improvements in morbidity and mortality. There are currently several classes of drugs available to target these pathways including phosphodiesterase-5 inhibitors (PDE5i), soluble guanylate cyclase (sGC) stimulators, prostacyclin class agents and endothelin receptor antagonists (ERAs). Combination therapy in PAH, either upfront or sequentially, has become a widely adopted treatment strategy, allowing for simultaneous targeting of more than one of these signaling pathways implicated in disease progression. Much of the current treatment landscape has focused on initial combination therapy with ambrisentan and tadalafil, an ERA and PDE5I respectively, following results of the AMBITION study demonstrating combination to be superior to either agent alone as upfront therapy. Consequently, clinicians often consider combination therapy with other drugs and drug classes, as deemed clinically appropriate, for patients with PAH. An alternative regimen that targets the NO and PGI2 pathways has been adopted by some clinicians as an effective and sometimes preferred therapeutic combination for PAH. Although there is a paucity of prospective data, preclinical data and results from secondary data analysis of clinical studies targeting these pathways may provide novel insights into this alternative combination as a reasonable, and sometimes preferred, alternative approach to combination therapy in PAH. This review of preclinical and clinical data will discuss the current understanding of combination therapy that simultaneously targets the NO and PGI2 signaling pathways, highlighting the clinical advantages and theoretical biochemical interplay of these agents.

This work reports on the performance of a segmented polymer electrochromic display that was fabricated with solution-based processes in ambient atmosphere. An encapsulation process and the combination of structured wells for the polymer electrochrome and electrolyte layers as well as the use of a preoxidized counter polymer yields high contrasts and fast switching speeds. Asymmetric driving-with respect to time-of the display is investigated for the first time and the degradation effects in the electrochrome layer are analyzed and addressed to yield a stable device exceeding 100,000 switching cycles. A printed circuit board was integrated with the display, allowing the device to be run as a clock, where the segments only required short pulses to switch without the need for a constant current to maintain its state. Such an application pairs well with the advantages of electrochromic polymers, drawing on its high contrast, stability, and ability to maintain its colored or colorless state without the need for a constant power supply, to demonstrate the promise as well as the challenges of developing more sophisticated electrochromic devices.

We report a straightforward strategy of accessing a wide variety of colors through simple predictive color mixing of electrochromic polymers (ECPs). We have created a set of brown ECP blends that can be incorporated as the active material in user-controlled electrochromic eyewear. Color mixing of ECPs proceeds in a subtractive fashion, and we acquire various hues of brown through the mixing of cyan and yellow primaries in combination with orange and periwinkle-blue secondary colors. Upon oxidation, all of the created blends exhibit a change in transmittance from ca. 10 to 70% in a few seconds. We demonstrate the attractiveness of these ECP blends as active materials in electrochromic eyewear by assembling user-controlled, high-contrast, fast-switching, and fully solution-processable electrochromic lenses with colorless transmissive states and colored states that correspond to commercially available sunglasses. The lenses were fabricated using a combination of inkjet printing and blade-coating to illustrate the feasibility of using soluble ECPs for high-throughput and large-scale processing.

Throughout the literature, a variety of counter electrode materials have been used in conjugated polymer-based electrochromic devices (ECDs) without a comparative understanding of their effects on the electrochromic properties of the device. In this study, we show that poor ECD performance, often attributed to electrochromic polymer (ECP) stability, is in fact largely due to an inappropriate choice of counter electrode. We have compared a set of counter electrode materials used in the ECD literature in magenta-to-clear and black-to-clear devices and evaluated how they affect the device parameters including contrast, switching time, stability, and voltage requirements. We demonstrate that through the appropriate choice of counter electrode material (i) the operating voltage can be lowered, (ii) no additional equilibration/break-in time is required, and (iii) the contrast and switching times of the ECP is maintained when incorporated into a device. Furthermore, we show that even unencapsulated ECDs with ECP-Magenta as the vibrantly colored material assembled and operated under ambient conditions can withstand over 10 000 switches without compromising contrast or switching time.

Shading systems have the potential to reduce energy consumption of electric lighting and improve visual comfort. Various automated control systems of shading device and electric lighting have been widely used. However, existing lighting and shading systems typically operate independently, i.e., information is not shared, and thus system performance is not optimal. Therefore, integrated control systems have been proposed to maximize energy efficiency and user comfort. Some problems are still unaddressed. For example, the benefits of sharing control information (e.g., HVAC state and occupancy information) between the lighting and shading control systems have not been quantified; the benefits of integrated controls have not been quantified. To address these issues, improved independent and integrated control strategies were proposed by adding shared HVAC state and occupancy information. To provide a quantitative comparison of these control strategies, a co-simulation platform consisting of BCVTB, EnergyPlus and Matlab was developed to perform an in-depth quantitative study of seven control strategies (manual, independent and integrated control strategies). Simulation results for a reference office building were presented for three climate zones (Baltimore, London, Abu-Dhabi), two types of blinds (interior, exterior) and two window-to-wall ratios (66%, 100%). A dynamic occupancy model was developed from actual office occupancy data and used in the simulations. The lighting, heating and cooling energy consumption, electric demand and visual comfort of different control strategies were evaluated and compared. Overall, in most cases, integrated lighting and daylight control outperforms all other strategies in energy and visual comfort performance.

We present a resistive network model, protein assay data, and outlook of the giant magnetoresistive (GMR) spin-valve magneto-nanosensor platform ideal for multiplexed detection of protein biomarkers in solutions. The magneto-nanosensors are designed to have optimal performance considering several factors such as sensor dimension, shape anisotropy, and magnetic nanoparticle tags. The resistive network model indicates that thinner spin-valve sensors with narrower width lead to higher signals from magnetic nanoparticle tags. Standard curves and real-time measurements showed a sensitivity of ~10 pM for phosphorylated-structural maintenance of chromosome 1 (phosphor-SMC1), ~53 fM for granulocyte colony stimulation factor (GCSF), and ~460 fM for interleukin-6 (IL6), which are among the representative biomarkers for radiation exposure and cancer.

The typical hedge fund incentive contract stipulates that 20 per cent of the profits are kept for the manager as an incentive to perform well: that is, provide large, persistent positive returns to investors. Rather than focusing on maximising their investor's wealth, managers may subvert this incentive scheme and focus on maximising assets under management instead. By doing so, managers may generate profits for themselves, even if their returns to their investors are small and do not persist. The aim of this work is to understand how a surviving manager may maximise monthly asset in-flow and minimise out-flow, and hence, maximise overall asset growth. Surprisingly, we find that non-return-based performance characteristics like fund age, relative performance, and fund size are key factors when forecasting monthly asset flow. Furthermore, we find that different causes of in- and out-flows exist.

In building retrofit projects, dynamic simulations are performed to simulate building performance. Uncertainty may negatively affect model calibration and predicted lighting energy savings, which increases the chance of default on performance-based contracts. Therefore, the aim of this paper is to develop a simulation-based method that can analyze lighting performance risk in lighting retrofit decisions. The model uses a surrogate model, which is constructed by adaptively selecting sample points and generating approximation surfaces with fast computing time. The surrogate model is a replacement of the computation intensive process. A statistical method is developed to generate extreme weather profile based on the 20-year historical weather data. A stochastic occupancy model was created using actual occupancy data to generate realistic occupancy patterns. Energy usage of lighting, and heating, ventilation, and air conditioning (HVAC) is simulated using EnergyPlus. The method can evaluate the influence of different risk factors (e.g., variation of luminaire input wattage, varying weather conditions) on lighting and HVAC energy consumption and lighting electricity demand. Probability distributions are generated to quantify the risk values. A case study was conducted to demonstrate and validate the methods. The surrogate model is a good solution for quantifying the risk factors and probability distribution of the building performance.

Nowadays, hospitals are ubiquitous and integral to modern society. Patients flow in and out of a veritable whirlwind of paperwork, consultations, and potential inpatient admissions, through an abstracted system that is not without flaws. One of the biggest flaws in the medical system is perhaps an unexpected one: the patient alarm system. One longitudinal study reported an 88.8% rate of false alarms, with other studies reporting numbers of similar magnitudes. These false alarm rates lead to deleterious effects that manifest in a lower standard of care across clinics. This paper discusses a model-based probabilistic inference approach to estimate physiological variables at a detection level. We design a generative model that complies with a layman's understanding of human physiology and perform approximate Bayesian inference. One primary goal of this paper is to justify a Bayesian modeling approach to increasing robustness in a physiological domain. In order to evaluate our algorithm we look at the application of heart beat detection using four datasets provided by PhysioNet, a research resource for complex physiological signals, in the form of the PhysioNet 2014 Challenge set-p1 and set-p2, the MIT-BIH Polysomnographic Database, and the MGH/MF Waveform Database. On these data sets our algorithm performs on par with the other top six submissions to the PhysioNet 2014 challenge. The overall evaluation scores in terms of sensitivity and positive predictivity values obtained were as follows: set-p1 (99.72%), set-p2 (93.51%), MIT-BIH (99.66%), and MGH/MF (95.53%). These scores are based on the averaging of gross sensitivity, gross positive predictivity, average sensitivity, and average positive predictivity.

To evaluate the indications and diagnoses made with 200 small bowel capsule endoscopies in an academic medical center.Wireless capsule endoscopy (PillCam SB) has recently become available as a new tool in the evaluation of patients with small bowel diseases. Its impact on patient care and usefulness in clinical practice has steadily been gaining ground, yet there are few studies that evaluate large numbers of patients.A retrospective review of wireless capsule endoscopies was performed between September 2003 and January 2005. Reviewed are the indications for the studies, number of complete and incomplete examinations, evaluation of gastric and small bowel transit times, findings made on examination, and the percent of diagnoses made and diagnoses suspected for each study indication.A total of 200 cases were reviewed. Indications included anemia (66% of cases), gastrointestinal hemorrhage (31% cases), abdominal pain (21% cases), diarrhea (11% cases), and other indications such as evaluation of abnormal radiographic findings or surveillance of inflammatory bowel disease (9% cases). The average patient age was 61.5 years (SD +/- 19.1 years). Males comprised 49% of patients. The wireless capsule endoscopy study completely evaluated the entire small bowel in 87% of cases. The most common cause for an incomplete examination was premature battery failure in 8% of cases. Only 9.5% of studies were normal without findings. Small bowel ulcerations were present in 38% of studies. Vascular ectasias were present in 23% of studies. Overall, a diagnosis was made in 23% of all studies, whereas a diagnosis was suspected based on the findings in an additional 31% of studies. The indication with the highest percentage of diagnoses made or suspected was gastrointestinal hemorrhage, with a diagnostic yield of 65%, followed by anemia 61%, diarrhea 36%, and pain 17%.Wireless capsule endoscopy is a valuable diagnostic tool in the evaluation of occult small bowel lesions, and was most effective in patients with gastrointestinal hemorrhage and anemia.

Due to the fluctuations in energy prices and the global warming effects as a result of pollution emission in the energy generation/conversion processes, energy conservation has gained much attention recently. The buildings in US consume significant amount of energy. Thus undertaking a building retrofitting project, in which new technology and features are added to the existing structure, can potentially both yield a good return on investment due to the future savings in energy consumption and reduce the negative environmental impact due to reduction in greenhouse gas emission. In this project, we study how to optimally perform energy retrofitting of existing building structures. Most existing methods either focus solely on minimizing energy consumption, while overlooking the financial incentives and occupant comfort, or aim at optimizing the energy related expenses under one particular deterministic setting and omitting the stochastic risks, such as volatility in energy pricing, weather uncertainties, in the operating environment. Hence, the building owners may not find the recommendation for building construction/recommendation relevant and profitable over its lifetime, and may not be willing to undertake such projects. This work proposes a novel risk management system on building energy retrofit, which uses a comprehensive optimization framework and considers both deterministic and stochastic factors. In one case study, we show that this system can improve the performance of the building under uncertainties while satisfying constraints imposed by occupant.

Today, most of the Manufacturing Execution Systems (MES) are monolithic, insufficiently configurable and difficult to modify. Using a distributed object-oriented technique, we will present a systematic approach, to develop a computer-integrated MES Framework which is open, modularized, distributed, configurable, interoperable, and maintainable. We start with the system analysis by collecting domain requirements and analysing domain knowledge. Our MES Framework is designed by the process of constructing an abstract object model based on domain knowledge, partitioning the application domain into components, identifying generic parts among components, defining framework messages, and developing design patterns for generic parts. After finishing the MES Framework design, we design a variety of functional components by inheriting appropriate design patterns of the Framework. An application can then be constructed by invoking corresponding methods of related components. The proposed MES Framework can be integra...

The creation and progress of OAK-TREE (One-of-a-Kind Traffic Research and Education Experiment) are chronicled. OAK-TREE is a traffic educational laboratory experiment that was developed and conducted at the University of California at Irvine (UCI) during the spring quarter of 1996. This project involved a cooperative effort between the academic community and public-sector transportation operating agencies in developing a comprehensive field and laboratory educational experience for undergraduate students in transportation engineering. The agencies involved in this effort were the Department of Civil and Environmental Engineering at the University of California at Irvine, the Advanced Traffic Surveillance and Control Center of the city of Los Angeles, the Transportation Management Center of the city of Anaheim, and the Irvine Traffic Research and Control Center of the city of Irvine. These agencies were instrumental in creating an innovative laboratory experience for academic training in the use of state-of-the-practice resources and methods for traffic engineering. The results were the development of a state-of-the-art traffic-control educational laboratory at UCI and the genesis of a unique traffic-control course that fulfilled the requirements of both fundamental academic education and rigorous professional training.

We report on the optimization of the capacitive behavior of poly(3,4-ethylenedioxythiophene) (PEDOT) films as polymeric electrodes in flexible, Type I electrochemical supercapacitors (ESCs) utilizing ionic liquid (IL) and organic gel electrolytes. The device performance was assessed based on figures of merit that are critical to evaluating the practical utility of electroactive polymer ESCs. PEDOT/IL devices were found to be highly stable over hundreds of thousands of cycles and could be reversibly charged/discharged at scan rates between 500 mV/s and 2 V/s depending on the polymer loading. Furthermore, these devices exhibit leakage currents and self-discharge rates that are comparable to state of the art electrochemical double-layer ESCs. Using an IL as device electrolyte allowed an extension of the voltage window of Type I ESCs by 60%, resulting in a 2.5-fold increase in the energy density obtained. The efficacies of tjese PEDOT ESCs were assessed by using them as a power source for a high-contrast and fast-switching electrochromic device, demonstrating their applicability in small organic electronic-based devices.

Acupuncture analgesia has been a common modality for management of acute and chronic pain. Acupuncture analgesia was based on the traditional Chinese medicine theory of the balance of Yin and Yang to regulate the Qi (energy) and blood. The Qi travels through various channels in the body via meridians. Although it is difficult to translate and poorly understood in Western scientific terms, both basic and clinical research on acupuncture analgesia has begun to expose substantial progress. There are correlations between acupuncture analgesia and the neural pathways such as afferent peripheral transduction and nerve transmission, ascending and descending modulation pathways, interpretation and central processing in the brain. Ongoing animal study models have yielded insight into acupuncture analgesia starting from behavioral observation and then dissect into the molecular level. Newer imaging techniques, e.g., functional magnetic resonance imaging (FMRI) and positron emission tomography (PET) scan have gradually revealed varying levels of neural modulation throughout central nervous system. Despite the deficiency of a vibrant consensus exploring the mechanism of its effect on analgesia, acupuncture has been shown to be beneficial in management of acute and chronic pain. Basic and clinical research has explored and compared electroacupuncture to manual acupuncture. There were greater analgesia and less intense pain during a brief period of electrical stimulation versus manual acupuncture. The clinical assessment and application of diverse frequencies and duration of electroacupuncture versus manual acupuncture may provide effective and systematic benefit. Further ongoing research is still in great demand in order to better elucidate the mechanism of acupuncture analgesia.

The purpose of this study is to use existing simulation tools to quantify the energy savings benefits of integrated control in office buildings. An EnergyPlus medium office benchmark simulation model (V1.0_3.0) developed by the Department of Energy (DOE) was used as a baseline model for this study. The baseline model was modified to examine the energy savings benefits of three possible control strategies compared to a benchmark case across 16 DOE climate zones. Two controllable subsystems were examined: (1) dimming of electric lighting, and (2) controllable window transmission. Simulation cases were run in EnergyPlus V3.0.0 for building window-to-wall ratios (WWR) of 33% and 66%. All three strategies employed electric lighting dimming resulting in lighting energy savings in building perimeter zones ranging from 64% to 84%. Integrated control of electric lighting and window transmission resulted in heating, ventilation, and air conditioning (HVAC) energy savings ranging from −1% to 40%. Control of electric lighting and window transmission with HVAC integration (seasonal schedule of window transmission control) resulted in HVAC energy savings ranging from 3% to 43%. HVAC energy savings decreased moving from warm climates to cold climates and increased when moving from humid, to dry, to marine climates.

The purpose of this study was to examine the effects of different sensor orientation on the positional accuracy of an AC electromagnetic tracking system, the second generation NDI Aurora, within a CT scanner environment. A three-axis positioning robot was used to move three electromagnetically tracked needles above the CT table throughout a 30cm by 30cm by 30cm volume sampled in 2.5cm steps. All three needle tips were held within 2mm of each other, with the needle axes orthogonally located in the +x, +y, and +z directions of the Aurora coordinate system. The corresponding position data was captured from the Aurora for each needle and was registered to the positioning system data using a rigid body transformation minimizing the least squares L2-norm. For all three needle orientations the largest errors were observed farthest from the field generator and closest to the CT table. However, the 3D distortion error patterns were different for each needle, demonstrating that the sensor orientation has an effect on the positional measurement of the sensor. This suggests that the effectiveness of using arrays of reference sensors to model and correct for metal distortions may depend strongly on the orientation of the reference sensors in relation to the orientation of the tracked device. In an ideal situation, the reference sensors should be oriented in the same direction as the tracked needle.

The purpose of this study was to quantify the effects of a computed tomography (CT) scanner environment on the positional accuracy of an AC electromagnetic tracking system, the second generation NDI Aurora. A three-axis positioning robot was used to move an electromagnetically tracked needle above the CT table throughout a 30cm by 30cm axial plane sampled in 2.5cm steps. The corresponding position data was captured from the Aurora and was registered to the positioning system data using a rigid body transformation minimizing the least squares L2-norm. Data was sampled at varying distances from the CT gantry (three feet, two feet, and one foot) and with the CT table in a nominal position and lowered by 10cm. A coordinate system was defined with the x axis normal to the CT table and the origin at the center of the CT table, and the z axis spanning the table in the lateral direction with the origin at the center of the CT table. In this coordinate system, the positional relationships of each sampled point, the CT table, and the Aurora field generator are clearly defined. This allows error maps to be displayed in accurate spatial relationship to the CT scanner as well as to a representative patient anatomy. By quantifying the distortions in relation to the position of CT scanner components and the Aurora field generator, the optimal working field of view and recommended guidelines for operation can be determined such that targeting inside human anatomy can be done with reasonable expectations of desired performance.

biliary stricture (62%) and choledocholithiasis (21%). Other indications included pancreatic duct stones, evaluation of IPMN, suspected biliary mass, and surveillance for cholangiocarcinoma. The clinical diagnosis was altered by Spyglass in 24% of indeterminate biliary stricture cases, most commonly from suspected malignant stricture to benign stricture. One patient with biliary obstruction caused by a hepatic lesion suspicious for metastasis, was found to have a hepatic abscess that was treated endoscopically. Management of stones (8 biliary, 1 pancreatic) with laser or electrohydraulic lithotripsy was successful in all cases. Complete clearance in a single session was achieved in all but one case, in which a heavy stone burden necessitated additional sessions. Cholangioscopic visualization alone was adequate for diagnosis in only 7% of cases, while pancreatoscopic visualization alone was adequate in 2/3 cases. Biopsy was performed in 24 cases, and yielded adequate tissue for histologic evaluation in 88%. The endoscopists’ impression was that the Spyglass procedure contributed meaningfully to patient management in 86% of cases. Procedure related complications occurred in 5 patients: 1) hemorrhage following sphincterotomy; 2) post-ERCP cholecystitis; 3) pancreatitis following pancreatoscopy; 4) post-procedure abdominal pain; and 5) congestive heart failure. Conclusions: The Spyglass system allows single-operator choledochoscopy and pancreatoscopy, high yield, endoscopically directed tissue sampling.and facilitates biliary and pancreatic lithotripsy. The nature and frequency of complications are within the spectrum of those reported with other interventional pancreaticobiliary procedures

In building retrofit projects, numerous sources of uncertainty about building performance need to be addressed. Deterministic simulations are usually used to estimate the potential performance difference from a baseline building. This approach needs building model calibration. Varying uncertain building parameters could lead to orders of magnitude simulation times. For example, in a lighting retrofit project, uncertainty (e.g., lamp input wattage, and varying weather conditions may negatively affect model calibration and lighting energy savings, which increases the chance of default on performance contract. Therefore, the aim of this paper is to develop a method that can conduct risk analysis based on building model (e.g., building information modelling). A stochastic occupancy model is used to simulate the occupancy pattern. Two lighting control strategies (occupancy and daylight controls) and two luminaire types (LED and fluorescent) are considered. Historical weather data is analyzed using statistical analysis, and the extreme weather conditions are generated to evaluate the impact of weather conditions on the lighting and HVAC energy usage. Then, EnergyPlus is used to simulate the energy usage based on different lamp types, control strategies, occupancy patterns, and weather conditions. A surrogate model is developed by using a small sample size of simulation data to construct an approximation surface to enable fast computing time. This method can evaluate impact of uncertainty of risk factors (e.g., occupancy level, luminaire type, weather) on lighting and HVAC energy usage and lighting electricity demand. This method can also prioritize risk factors based on sensitivity analysis on building performance and help users to choose different lamp types to minimize risks.