Combined Behavioral and Engineering Approach to Preventing Highway Fatalities

Traditional, single-discipline highway safety approaches can be augmented through multidisciplinary approaches that consider both engineering and behavioral interventions (e.g., education, enforcement, public outreach campaigns). Leveraging a systems-based conceptual framework of roadway safety, multiple forms of statistical and geospatial analysis, and SPF modeling and network screening, this report proposes and demonstrates methods for unpacking the influence of behavioral-related factors on crash occurrences and outcomes. The primary focus is on behaviors targeted in the Strategic Highway Safety Plan — aggressive driving, distracted driving, impaired driving, and driving without proper restraint (i.e., seatbelts). Based on application of these methods, the report highlights areas and highway corridors in Kentucky where behavioral-related crashes have been most common. Practitioners can use methods presented in the report to locate areas where behavioral-related crashes are problematic and based on this knowledge design behavioral modification strategies and countermeasures which focus on at-risk populations

Mast Cell–Derived Particles Deliver Peripheral Signals to Remote Lymph Nodes

During infection, signals from the periphery are known to reach draining lymph nodes (DLNs), but how these molecules, such as inflammatory cytokines, traverse the significant distances involved without dilution or degradation remains unclear. We show that peripheral mast cells, upon activation, release stable submicrometer heparin-based particles containing tumor necrosis factor and other proteins. These complexes enter lymphatic vessels and rapidly traffic to the DLNs. This physiological drug delivery system facilitates communication between peripheral sites of inflammation and remote secondary lymphoid tissues

Constructing Search Spaces for Search-Based Software Testing Using Neural Networks

A central requirement for any Search-Based Software Testing (SBST) technique is a convenient and meaningful fitness landscape. Whether one follows a targeted or a diversification driven strategy, a search landscape needs to be large, continuous, easy to construct and representative of the underlying property of interest. Constructing such a landscape is not a trivial task often requiring a significant manual effort by an expert. We present an approach for constructing meaningful and convenient fitness landscapes using neural networks (NN) – for targeted and diversification strategies alike. We suggest that output of an NN predictor can be interpreted as a fitness for a targeted strategy. The NN is trained on a corpus of execution traces and various properties of interest, prior to searching. During search, the trained NN is queried to predict an estimate of a property given an execution trace. The outputs of the NN form a convenient search space which is strongly representative of a number of properties. We believe that such a search space can be readily used for driving a search towards specific properties of interest. For a diversification strategy, we propose the use of an autoencoder; a mechanism for compacting data into an n-dimensional “latent” space. In it, datapoints are arranged according to the similarity of their salient features. We show that a latent space of execution traces possesses characteristics of a convenient search landscape: it is continuous, large and crucially, it defines a notion of similarity to arbitrary observations

Stable Dry Powder Formulation for Nasal Delivery of Anthrax Vaccine

There is a current biodefense interest in protection against Anthrax. Here we developed a new generation of stable and effective anthrax vaccine. We studied the immune response elicited by rPA delivered intranasally with a novel mucosal adjuvant, a mast cell activator Compound 48/80. The vaccine formulation was prepared in a powder form by spray-freeze-drying (SFD) under optimized conditions to produce particles with a target size of D50=25μm, suitable for delivery to the rabbit nasal cavity. Physicochemical properties of the powder vaccines were characterized to assess their delivery and storage potential. Structural stability of rPA was confirmed by CD and ATR-FTIR, while functional stability of rPA and C48/80 was monitored by cell-based assays. Animal study was performed using a unitdose powder device for direct nasal application. Results showed that C48/80 provided effective mucosal adjuvant activity in rabbits. Freshly prepared SFD powder vaccine formulations or powders stored for over two years at room temperature elicited significantly elevated serum PA-specific and lethal toxin neutralization antibody titers that were comparable to that induced by IM immunization with rPA. Nasal delivery of this vaccine formulation may be a viable alternative to the currently licensed vaccine, or an attractive vaccine platform for other mucosally transmitted diseases

Pathologist Concordance for Ovarian Carcinoma Subtype Classification and Identification of Relevant Histologic Features Using Microscope and Whole Slide Imaging.

CONTEXT.—: Despite several studies focusing on the validation of whole slide imaging (WSI) across organ systems or subspecialties, the use of WSI for specific primary diagnosis tasks has been underexamined. OBJECTIVE.—: To assess pathologist performance for the histologic subtyping of individual sections of ovarian carcinomas using a light microscope and WSI. DESIGN.—: A panel of 3 experienced gynecologic pathologists provided reference subtype diagnoses for 212 histologic sections from 109 ovarian carcinomas based on optical microscopy review. Two additional attending pathologists provided diagnoses and also identified the presence of a set of 8 histologic features important for ovarian tumor subtyping. Two experienced gynecologic pathologists and 2 fellows reviewed the corresponding WSI images for subtype classification and feature identification. RESULTS.—: Across pathologists specialized in gynecologic pathology, concordance with the reference diagnosis for the 5 major ovarian carcinoma subtypes was significantly higher for a pathologist reading on a microscope than each of 2 pathologists reading on WSI. Differences were primarily due to more frequent classification of mucinous carcinomas as endometrioid with WSI. Pathologists had generally low agreement in identifying histologic features important to ovarian tumor subtype classification with either an optical microscopy or WSI. This result suggests the need for refined histologic criteria for identifying such features. Interobserver agreement was particularly low for identifying intracytoplasmic mucin with WSI. Inconsistencies in evaluating nuclear atypia and mitoses with WSI were also observed. CONCLUSIONS.—: Further research is needed to specify the reasons for these diagnostic challenges and to inform users and manufacturers of WSI technology

Management of Intrathecal Catheter-Tip Inflammatory Masses: A Consensus Statement

In a companion article, we synthesized current clinical and preclinical data to formulate hypotheses about the etiology of drug administration catheter-tip inflammatory masses. In this article, we communicate our recommendations for the detection, treatment, mitigation, and prevention of such masses. Methods. We reviewed published and unpublished case reports and our own experiences to find methods to diagnose and treat catheter-tip inflammatory masses in a manner that minimized adverse neurological sequelae. We also formulated hypotheses about theoretical ways to mitigate, and possibly, prevent the formation of such masses. Results. Human cases have occurred only in patients with chronic pain who received intrathecal opioid drugs, alone or mixed with other drugs, or in patients who received agents that were not labeled for long-term intrathecal use. Most patients had noncancer pain owing to their large representation among the population with implanted pumps. Such patients also had a longer life expectancy and exposure to intrathecal drugs, and they received higher daily doses than patients with cancer pain. Clues to diagnosis included the loss of analgesic drug effects accompanied by new, gradually progressive neurological symptoms and signs. When a mass was diagnosed before it filled the spinal canal or before it caused severe neurological symptoms, open surgery to remove the mass often was not required. Anecdotal reports and the authors' experiences suggest that cessation of drug administration through the affected catheter was followed by shrinkage or disappearance of the mass over a period of 2-5 months. Conclusions. Attentive follow-up and maintenance of an index of suspicion should permit timely diagnosis, minimally invasive treatment, and avoidance of neurological injury from catheter-tip inflammatory masses. Whenever it is feasible, positioning the catheter in the lumbar thecal sac and/or keeping the daily intrathecal opioid dose as low as possible for as long possible may mitigate the seriousness, and perhaps, reduce the incidence of such inflammatory masses.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75020/1/j.1526-4637.2002.02055.x.pd

Salmonella Typhimurium Impedes Innate Immunity with a Mast-Cell-Suppressing Protein Tyrosine Phosphatase, SptP

The virulence of Salmonella is linked to its invasive capacity and suppression of adaptive immunity. This does not explain, however, the rapid dissemination of the pathogen after breaching the gut. Here we showed that early in infection, S. Typhimurium suppressed degranulation of local mast cells (MCs), resulting in limited neutrophil recruitment and restricted outflow of vascular contents into infection sites, thus facilitating bacterial spread. MC suppression was mediated by the Salmonella phosphatase (SptP), which shares structural homology with Yersinia YopH. SptP functioned by dephosphorylating the vesicle fusion protein N-ethylmalemide-sensitive factor (NSF) and by blocking phosphorylation of Syk. Without SptP, orally challenged S. Typhimurium failed to suppress MC degranulation and exhibited limited colonization of the mesenteric lymph nodes. Administration of SptP to sites of Escherichia coli infection markedly enhanced its virulence. Thus, SptP-mediated inactivation of local MCs is a powerful mechanism utilized by S. Typhimurium to impede early innate immunity

Affordances, constraints and information flows as ‘leverage points’ in design for sustainable behaviour

Copyright @ 2012 Social Science Electronic PublishingTwo of Donella Meadows' 'leverage points' for intervening in systems (1999) seem particularly pertinent to design for sustainable behaviour, in the sense that designers may have the scope to implement them in (re-)designing everyday products and services. The 'rules of the system' -- interpreted here to refer to affordances and constraints -- and the structure of information flows both offer a range of opportunities for design interventions to in fluence behaviour change, and in this paper, some of the implications and possibilities are discussed with reference to parallel concepts from within design, HCI and relevant areas of psychology