Applying the adaptive model of comfort

This note is directed to one major aspect of the comfort of building occupants &ndash; namely, thermal comfort. Even though it may be difficult to isolate thermal sensations from the whole of comfort itself, humans have a strong physiological connection with their thermal environment. Our thermal perceptions and sensations often vary greatly, especially between our indoor and outdoor environments. We may be totally comfortable lounging under a shade cloth on a 35&deg;C day with a stiff breeze enveloping our body, but would never tolerate similar conditions indoors. Such divergent perceptions of the same thermal stimulus across differing contexts raise countless questions about just what the determinants of thermal comfort actually are, and how they may be managed against the demands for an environmentally responsive architecture. <br /

Validation of the Fiala multi-node thermophysiological model for UTCI application

The important requirement that COST Action 730 demanded of the physiological model to be used for the Universal Thermal Climate Index (UTCI) was its capability of accurate simulation of human thermophysiological responses across a wide range of relevant environmental conditions, such as conditions corresponding to the selection of all habitable climates and their seasonal changes, and transient conditions representing the temporal variation of outdoor conditions. In the first part of this study, available heat budget/two-node models and multi-node thermophysiological models were evaluated by direct comparison over a wide spectrum of climatic conditions. The UTCI-Fiala model predicted most reliably the average human thermal response, as shown by least deviations from physiologically plausible responses when compared to other models. In the second part of the study, this model was subjected to extensive validation using the results of human subject experiments for a range of relevant (steady-state and transient) environmental conditions. The UTCI-Fiala multi-node model proved its ability to predict adequately the human physiological response for a variety of moderate and extreme conditions represented in the COST 730 database. The mean skin and core temperatures were predicted with average root-mean-square deviations of 1.35 ± 1.00°C and 0.32 ± 0.20°C, respectivel

Validation of the Fiala multi-node thermophysiological model for UTCI application

The important requirement that COST Action 730 demanded of the physiological model to be used for the Universal Thermal Climate Index was its capability of accurate simulation of the human thermophysiological responses across a wide range of relevant environmental conditions, such as conditions corresponding to the selection of all habitable climates and their seasonal changes, and transient conditions representing temporal variation of outdoor conditions. In the first part of this study available heat budget/two-node models and multi-node thermophysiological models were evaluated by direct comparison over the wide spectrum of climatic conditions. The UTCI-Fiala model predicted most reliably the average human thermal response which was showed by least deviations from physiologically plausible responses when compared to other models. In the second part of the study, this model was, therefore, subjected to extensive validation using results of human subject experiments for a range of relevant (steady-state and transient) environmental conditions. The UTCI-Fiala multi-node model proved its ability to predict adequately the human physiological response for a variety of moderate and extreme conditions represented in the COST 730 database. The mean skin and core temperatures were predicted with average root-meansquare deviations of 1.35 ± 1.00 °C and 0.32 ± 0.20 °C, respectively

Piezo1 integration of vascular architecture with physiological force

The mechanisms by which physical forces regulate endothelial cells to determine the complexities of vascular structure and function are enigmatic¹⁻⁵. Studies of sensory neurons have suggested Piezo proteins as subunits of Ca²⁺-permeable non-selective cationic channels for detection of noxious mechanical impact⁶⁻⁸. Here we show Piezo1 (Fam38a) channels as sensors of frictional force (shear stress) and determinants of vascular structure in both development and adult physiology. Global or endothelial-specific disruption of mouse Piezo1 profoundly disturbed the developing vasculature and was embryonic lethal within days of the heart beating. Haploinsufficiency was not lethal but endothelial abnormality was detected in mature vessels. The importance of Piezo1 channels as sensors of blood flow was shown by Piezo1 dependence of shear-stress-evoked ionic current and calcium influx in endothelial cells and the ability of exogenous Piezo1 to confer sensitivity to shear stress on otherwise resistant cells. Downstream of this calcium influx there was protease activation and spatial reorganization of endothelial cells to the polarity of the applied force. The data suggest that Piezo1 channels function as pivotal integrators in vascular biology

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome