Physical and thermal strain of firefighters according to the firefighting tactics used to suppress wildfires

The aim of this study was to analyse the physiological strain of firefighters, using heart rate (HR) and core temperature, during real wildfire suppression according to the type of attack performed (direct, indirect or mixed). Three intensity zones were established according to the HR corresponding to the ventilatory threshold (VT) and respiratory compensation threshold (RCT): zone 1, RCT. The exercise workload (training impulse (TRIMP)), the physiological strain index (PSI) and the cumulative heat strain index(CHSI) were calculated using the time spent in each zone, and the HR and core temperature, respectively. Significantly higher mean HR, time spent in Z2 and Z3 and TRIMP h(-1) were found in direct and mixed versus indirect attacks. The highest PSI and CHSI were observed in the direct attack. In conclusion, exercise strain and combined thermal strain, but not core temperature during wildfire suppression, are related to the type of attack performed. STATEMENT OF RELEVANCE: Our findings demonstrated that wildfire firefighting is associated with high physiological demands, which vary significantly depending on the tactics chosen for performing the task. These results should be kept in mind when planning programmes to improve wildland firefighters' physical fitness, which will allow improvement in their performance.     

Molecular modeling optimization of anticoagulant pyridine derivatives

Intravascular clotting remains a major health problem in the United States, the most prominent being deep vein thrombosis, pulmonary embolism and thromboembolic stroke. Previous reports on the use of pyridine derivatives in cardiovascular drug development encourage us to pursue new types of compounds based on a pyridine scaffold. Eleven pyridine derivatives (oximes, semicarbazones, N-oxides) previously synthesized in our laboratories were tested as anticoagulants on pooled normal plasma using the prothrombin time (PT) protocol. The best anticoagulant within the oxime series was compound AF4, within the oxime N-oxide series was compound AF4-N-oxide, and within the semicarbazone series, compound MD1-30Y. We also used a molecular modeling approach to guide our efforts, and found that there was good correlation between coagulation data and computational energy scores. Molecular docking was performed to target the active site of thrombin with the DOCK v5.2 package. The results of molecular modeling indicate that improvement in anticoagulant activities can be expected by functionalization at the three-position of the pyridine ring and by N-oxide formation. Results reported here prove the suitability of DOCK in the lead optimization process.     

High-resolution biomarker discovery: Moving from large-scale proteome profiling to quantitative validation of lead candidates

Diverse proteomic techniques based on protein MS have been introduced to systematically characterize protein perturbations associated with disease. Progress in clinical proteomics is essential for personalized medicine, wherein treatments will be tailored to individual needs based on patient stratification using noninvasive disease monitoring procedures to reveal the most appropriate therapeutic targets. However, breakthroughs await the successful development and application of a robust proteomic pipeline capable of identifying and rigorously assessing the relevance of multiple candidate proteins as informative diagnostic and prognostic indicators or suitable drug targets involved in a pathological process. While steady progress has been made toward more comprehensive proteome profiling, the emphasis must now shift from in depth screening of reference samples to stringent quantitative validation of selected lead candidates in a broader clinical context. Here, we present an overview of the emerging proteomic strategies for high-throughput protein detection focused primarily on targeted MS/MS as the basis for biomarker verification in large clinical cohorts. We discuss the conceptual promise and practical pitfalls of these methods in terms of achieving higher dynamic range, higher throughput, and more reliable quantification, highlighting research avenues that merit additional inquiry.     

Method of imaging low density lipoproteins by atomic force microscopy

This short paper reports a simple method to image low density lipoproteins (LDL) using atomic force microscopy (AFM). This instrument allows imaging of biological samples in liquid and presents the advantage of needing no sample preparation such as staining or fixation that may affect their general structure. Dimensions (diameter and height) of individual LDL particles were successfully measured. AFM imaging revealed that LDL have a quasi-spherical structure on the x and y axis with an oblate spheroid structure in the z axis (i.e., height). LDLs were found to have an average diameter of 23 +/- 3 nm. The obtained mean height was 10 +/- 2 nm.     

Anticipating the content and circumstances of skill transfer: unrealistic expectations of driver training and graduated licensing?

There is substantial evidence that driving skills improve during driver training, but the long-term safety benefit of such formal training remains unproven. Restricting the exposure of newly licensed drivers to more hazardous driving circumstances, as in graduated driver licensing (GDL) regimes, demonstrably reduces crash risk, but drivers remain at risk after the restrictions are eased. GDL and most other licensing regimes advocate increased basic training and practice, but thereafter require neither advanced training nor systematic increase in exposure to risk. This assumes that basic skills acquired during formal training will transfer positively to new and more demanding traffic circumstances. This paper reviews the theoretical basis for these assumptions and offers a way of systematically identifying the extent of transfer desired. It is concluded that there is little theoretical or empirical foundation for the supposition that what is learned during or after training will have a safety benefit in later driving.     

Molecular dynamics at the receptor level of immunodominant myelin basic protein epitope 87-99 implicated in multiple sclerosis and its antagonists altered peptide ligands: triggering of immune response

This work reports molecular dynamics studies at the receptor level of the immunodominant myelin basic protein (MBP) epitope 87-99 implicated in multiple sclerosis, and its antagonists altered peptide ligands (APLs), namely [Arg91, Ala96] MBP87-99 and [Ala91,96] MBP87-99. The interaction of each peptide ligand with the receptor human leukocyte antigen HLA-DR2b was studied, starting from X-ray structure with pdb code: 1ymm. This is the first such study of APL-HLA-DR2b complexes, and hence the first attempt to gain a better understanding of the molecular recognition mechanisms that underlie TCR antagonism by these APLs. The amino acids His88 and Phe89 serve as T-cell receptor (TCR) anchors in the formation of the trimolecular complex TCR-peptide-HLA-DR2b, where the TCR binds in a diagonal, off-centered mode to the peptide-HLA complex. The present findings indicate that these two amino acids have a different orientation in the APLs [Arg91, Ala96] MBP87-99 and [Ala91,96] MBP87-99: His88 and Phe89 remain buried in HLA grooves and are not available for interaction with the TCR. We propose that this different topology could provide a possible mechanism of action for TCR antagonism.     

Toward the improvement of image-guided interventions for minimally invasive surgery: three factors that affect performance

OBJECTIVES: The objectives were to measure the impact of specific features of imaging devices on tasks relevant to minimally invasive surgery (MIS) and to investigate cognitive and perceptual factors in such tasks. BACKGROUND: Although image-guided interventions used in MIS provide benefits for patients, they pose drawbacks for surgeons, including degraded depth perception and reduced field of view (FOV). It is important to identify design factors that affect performance. METHOD: In two navigation experiments, observers fed a borescope through an object until it reached a target. Task completion time and object shape judgments were measured. In a motion perception experiment, observers reported the direction of a line that moved behind an aperture. A motion illusion associated with reduced FOV was measured. RESULTS: Navigation through an object was faster when a preview of the object's exterior was provided. Judgments about the object's shape were more accurate with a preview (compared with none) and with active viewing (compared with passive viewing). The motion illusion decreased with a rectangular or rotating octagonal viewing aperture (compared with circular). CONCLUSIONS: Navigation performance may be enhanced when surgeons develop a mental model of the surgical environment, when surgeons (rather than assistants) control the camera, and when the shape of the image is designed to reduce visual illusions. APPLICATION: Unintentional contact between surgical tools and healthy tissues may be reduced during MIS when (a) visual aids permit surgeons to maintain a mental model of the surgical environment, (b) images are bound by noncircular apertures, and (c) surgeons manually control the camera.     

3D distance fields: a survey of techniques and applications

A distance field is a representation where, at each point within the field, we know the distance from that point to the closest point on any object within the domain. In addition to distance, other properties may be derived from the distance field, such as the direction to the surface, and when the distance field is signed, we may also determine if the point is internal or external to objects within the domain. The distance field has been found to be a useful construction within the areas of computer vision, physics, and computer graphics. This paper serves as an exposition of methods for the production of distance fields, and a review of alternative representations and applications of distance fields. In the course of this paper, we present various methods from all three of the above areas, and we answer pertinent questions such as How accurate are these methods compared to each other? How simple are they to implement?, and What is the complexity and runtime of such methods?     

Incorporating biologically based models into assessments of risk from chemical contaminants

The general approach to assessment of risk from chemical contaminants in drinking water involves three steps: hazard identification, exposure assessment, and dose-response assessment. Traditionally, the risks to humans associated with different levels of a chemical have been derived from the toxic responses observed in animals. It is becoming increasingly clear, however, that further information is needed if risks to humans are to be assessed accurately. Biologically based models help clarify the dose-response relationship and reduce uncertainty.     

Incremental backprojection algorithm: modification of the searching flow scheme and utilization of the relationship among projection views

A two-dimensional (2-D) search flow scheme is proposed for the incremental backprojection algorithm. In this scheme, the searching direction in a beam is determined only by the distance from the current pixel to the corresponding ray; no pixels outside the beam are involved in the procedure. In addition, the geometrical relationships between the image grids and the projection rays in different views are fully exploited to further reduce the search operations. It is found that backprojection of four views can be performed at the same time, and the search operation is only required for one of them if the number of views is even. Thus, backprojection is accomplished on a quartet-by-quartet of views basis as well as on beam-by-beam basis. These approaches not only minimize the number of search operations but also possess a simple algorithm structure. Implementation results obtained with an AST-386 computer for the incremental backprojection algorithm using this search flow scheme and the relationship among projection views show that the processing time can be reduced by a factor of about 2.