Experimental Validation of Methods for Prophylaxis against Deep Venous Thrombosis: A Review and Proposal

The experimental procedure by which the valve cusp hypoxia (VCH) hypothesis of the etiology of deep venous thrombosis (DVT) was confirmed lends itself to testing of methods of prophylaxis. Similar animal experiments could end the present exclusive reliance on statistical analysis of data from large patient cohorts to evaluate prophylactic regimes. The reduction of need for such (usually retrospective) analyses could enable rationally-based clinical trials of prophylactic methods to be conducted more rapidly, and the success of such trials would lead to decreased incidences of DVT-related mortality and morbidity. This paper reviews the VCH hypothesis (“VCH thesis”, following its corroboration) and its implications for understanding DVT and its sequelae, and outlines the experimental protocol for testing prophylactic methods. The advantages and limitations of the protocol are briefly discussed

Evaluation of a Graphical Anesthesia Drug Display for Space Travel

As the frequency and duration of space travel increase, the potential need for emergency medical care in space grows, and with it the need for patient monitoring devices supporting therapeutic treatment. Providing emergency care to an injured astronaut may necessitate immediate surgery. During such events, the timely administration of anesthetic agents will need to be performed by someone who is not a formally trained anesthesiologist. The availability of usable real-time displays of intravenous anesthetic concentrations and effects could significantly enhance intraoperative clinical decision-making both in space and on earth. The effectiveness of the real-time anesthesia display on the management of total intravenous anesthesia was determined by 31 anesthesiologists participating in a simulation study. In the presence of the anesthesia drug display, clinicians maintained physiologic indicators such as blood pressure and heart rate closer to baseline levels. Participants also reported an increase in perceived performance when using the drug display. The results indicate that surgeries on earth and in orbit would benefit from the implementation of this display

On the Tail of the Scottish Vowel Length Rule in Glasgow

One of the most famous sound features of Scottish English is the short/long timing alternation of /i u ai/vowels, which depends on the morpho-phonemic environment, and is known of as the Scottish Vowel Length Rule (SVLR). These alternations make the status of vowel quantity in Scottish English (quasi-)phonemic but are also susceptible to change, particularly in situations of intense sustained dialect contact with Anglo-English. Does the SVLR change in Glasgow where dialect contact at the community level is comparably low? The present study sets out to tackle this question, and tests two hypotheses involving (1) external influences due to dialect-contact and (2) internal, prosodically-induced factors of sound change. Durational analyses of /i u a/ were conducted on a corpus of spontaneous Glaswegian speech from the 1970s and 2000s, and four speaker groups were compared, two of middle-aged men, and two of adolescent boys. Our hypothesis that the development of the SVLR over time may be internally constrained and interact with prosody was largely confirmed. We observed weakening effects in its implementation which were localised in phrase-medial unaccented positions in all speaker groups, and in phrase-final positions in the speakers born after the Second World War. But unlike some other varieties of Scottish or Northern English which show weakening of the Rule under a prolonged contact with Anglo-English, dialect contact seems to be having less impact on the durational patterns in Glaswegian vernacular, probably because of the overall reduced potential for a regular, everyday contact in the West given the different demographies

EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA); Scientific Opinion on principles for deriving and applying Dietary Reference Values

This Opinion of the EFSA Panel on Dietetic products, Nutrition, and Allergies (NDA) deals with the general principles for development and application of Dietary Reference Values (DRVs). These quantitative reference values for nutrient intakes for healthy individuals and populations are based on health criteria. Derived from DRVs, nutrients goals and recommendations take into account other criteria such as food composition or dietary habits, and may be used for assessment and planning of diets. It is proposed to derive the following DRVs: 1) Population Reference Intakes (PRI), 2) Average Requirement (AR), 3) Lower Threshold Intake (LTI), 4) Adequate Intake (AI), 5) Reference Intake ranges for macronutrients (RI). Nutrient requirements differ with age, sex and physiological condition. The Panel proposes to define the age ranges used for each nutrient on a case-by-case basis depending on the available data. For the age group < 6 months requirements are considered to be equal to the supply from breast- milk, except in those cases where this does not apply. Separate reference values will be established for pregnant and lactating women. Interpolation or extrapolation between population groups will be used in instances where no data are available for defined age and sex groups

Pulmonary Metaphor Design and Anesthesia Simulation Testing

Medical decision making is a crucial process to successfully treat a critical medical emergency. During an unexpected medical event, astronauts, like anesthesiologists, must react quickly in a complex environment. Tools, such as the pulmonary metaphor display, were created to aid the medical caregiver\u27s decision making process. The pulmonary metaphor display is designed to help the caregiver collect and integrate pulmonary data to provide a more accurate, quicker diagnosis and treatment. The following outline anesthesiology simulation study will provide the data to prove that the pulmonary metaphor display is beneficial to medical decision making

Editorial: hypotheses about protein folding - the proteomic code and wonderfolds

Theoretical biology journals can contribute in many ways to the progress of knowledge. They are particularly well-placed to encourage dialogue and debate about hypotheses addressing problematical areas of research. An online journal provides an especially useful forum for such debate because of the option of posting comments within days of the publication of a contentious article

Hydrophilicity Matching – A Potential Prerequisite for the Formation of Protein-Protein Complexes in the Cell

A binding event between two proteins typically consists of a diffusional search of binding partners for one another, followed by a specific recognition of the compatible binding sites resulting in the formation of the complex. However, it is unclear how binding partners find each other in the context of the crowded, constantly fluctuating, and interaction-rich cellular environment. Here we examine the non-specific component of protein-protein interactions, which refers to those physicochemical properties of the binding partners that are independent of the exact details of their binding sites, but which can affect their localization or diffusional search for one another. We show that, for a large set of high-resolution experimental 3D structures of binary, transient protein complexes taken from the DOCKGROUND database, the binding partners display a surprising, statistically significant similarity in terms of their total hydration free energies normalized by a size-dependent variable. We hypothesize that colocalization of binding partners, even within individual cellular compartments such as the cytoplasm, may be influenced by their relative hydrophilicity, potentially in response to local hydrophilic gradients

On the thermodynamic origin of metabolic scaling

This work has been funded by projects AYA2013-48623-C2-2, FIS2013-41057-P, CGL2013-46862-C2-1-P and SAF2015-65878-R from the Spanish Ministerio de Economa y Competitividad and PrometeoII/2014/086, PrometeoII/2014/060 and PrometeoII/2014/065 from the Generalitat Valenciana (Spain). BL acknowledges funding from a Salvador de Madariaga fellowship, and L.L. acknowledges funding from EPSRC Early Career fellowship EP/P01660X/1

Systematic Evaluation of the Descriptive and Predictive Performance of Paediatric Morphine Population Models

Purpose: A framework for the evaluation of paediatric population models is proposed and applied to two different paediatric population pharmacokinetic models for morphine. One covariate model was based on a systematic covariate analysis, the other on fixed allometric scaling principles. Methods: The six evaluation criteria in the framework were 1) number of parameters and condition number, 2) numerical diagnostics, 3) prediction-based diagnostics, 4) η-shrinkage, 5) simulation-based diagnostics, 6) diagnostics of individual and population parameter estimates versus covariates, including measurements of bias and precision of the population values compared to the observed individual values. The framework entails both an internal and external model evaluation procedure. Results: The application of the framework to the two models resulted in the detection of overparameterization and misleading diagnostics based on individual predictions caused by high shrinkage. The diagnostic of individual and population parameter estimates versus covariates proved to be highly informative in assessing obtained covariate relationships. Based on the framework, the systematic covariate model proved to be superior over the fixed allometric model in terms of predictive performance. Conclusions: The proposed framework is suitable for the evaluation of paediatric (covariate) models and should be applied to corroborate the descriptive and predictive properties of these models