Cortical gene expression architecture links healthy neurodevelopment to the imaging, transcriptomics and genetics of autism and schizophrenia.

Human brain organization involves the coordinated expression of thousands of genes. For example, the first principal component (C1) of cortical transcription identifies a hierarchy from sensorimotor to association regions. In this study, optimized processing of the Allen Human Brain Atlas revealed two new components of cortical gene expression architecture, C2 and C3, which are distinctively enriched for neuronal, metabolic and immune processes, specific cell types and cytoarchitectonics, and genetic variants associated with intelligence. Using additional datasets (PsychENCODE, Allen Cell Atlas and BrainSpan), we found that C1-C3 represent generalizable transcriptional programs that are coordinated within cells and differentially phased during fetal and postnatal development. Autism spectrum disorder and schizophrenia were specifically associated with C1/C2 and C3, respectively, across neuroimaging, differential expression and genome-wide association studies. Evidence converged especially in support of C3 as a normative transcriptional program for adolescent brain development, which can lead to atypical supragranular cortical connectivity in people at high genetic risk for schizophrenia.

Transcriptional cartography integrates multiscale biology of the human cortex.

The cerebral cortex underlies many of our unique strengths and vulnerabilities, but efforts to understand human cortical organization are challenged by reliance on incompatible measurement methods at different spatial scales. Macroscale features such as cortical folding and functional activation are accessed through spatially dense neuroimaging maps, whereas microscale cellular and molecular features are typically measured with sparse postmortem sampling. Here, we integrate these distinct windows on brain organization by building upon existing postmortem data to impute, validate, and analyze a library of spatially dense neuroimaging-like maps of human cortical gene expression. These maps allow spatially unbiased discovery of cortical zones with extreme transcriptional profiles or unusually rapid transcriptional change which index distinct microstructure and predict neuroimaging measures of cortical folding and functional activation. Modules of spatially coexpressed genes define a family of canonical expression maps that integrate diverse spatial scales and temporal epochs of human brain organization - ranging from protein-protein interactions to large-scale systems for cognitive processing. These module maps also parse neuropsychiatric risk genes into subsets which tag distinct cyto-laminar features and differentially predict the location of altered cortical anatomy and gene expression in patients. Taken together, the methods, resources, and findings described here advance our understanding of human cortical organization and offer flexible bridges to connect scientific fields operating at different spatial scales of human brain research.

Two human brain systems micro-structurally associated with obesity.

The relationship between obesity and human brain structure is incompletely understood. Using diffusion-weighted MRI from ∼30,000 UK Biobank participants, we test the hypothesis that obesity (waist-to-hip ratio, WHR) is associated with regional differences in two micro-structural MRI metrics: isotropic volume fraction (ISOVF), an index of free water, and intra-cellular volume fraction (ICVF), an index of neurite density. We observed significant associations with obesity in two coupled but distinct brain systems: a prefrontal/temporal/striatal system associated with ISOVF and a medial temporal/occipital/striatal system associated with ICVF. The ISOVF~WHR system colocated with expression of genes enriched for innate immune functions, decreased glial density, and high mu opioid (MOR) and other neurotransmitter receptor density. Conversely, the ICVF~WHR system co-located with expression of genes enriched for G-protein coupled receptors and decreased density of MOR and other receptors. To test whether these distinct brain phenotypes might differ in terms of their underlying shared genetics or relationship to maps of the inflammatory marker C-reactive Protein (CRP), we estimated the genetic correlations between WHR and ISOVF (rg = 0.026, P = 0.36) and ICVF (rg = 0.112, P < 9×10-4) as well as comparing correlations between WHR maps and equivalent CRP maps for ISOVF and ICVF (P<0.05). These correlational results are consistent with a two-way mechanistic model whereby genetically determined differences in neurite density in the medial temporal system may contribute to obesity, whereas water content in the prefrontal system could reflect a consequence of obesity mediated by innate immune system activation.

People with obesity are at greater risk of cardiovascular diseases and metabolic conditions such as type 2 diabetes. More recently obesity has also been linked to changes in the brain that are associated with age-related dementia and cognitive decline. This includes a thinner cortex (the brain's outer layer) and lower volume of grey matter which is where cognitive processes, such as learning, take place. However, questions remain about how obesity and grey matter are connected. For instance, it is unclear whether the change in volume is due to there being fewer cells (and thus more water between them) or fewer connections between cells in these brain areas. It is also unknown whether the reduced volume of grey matter is a cause or consequence of obesity. To address these questions, Kitzbichler et al. analysed 30,000 MRI scans of the human brain which are stored in the UK Biobank. This revealed two characteristics in grey matter that were linked to obesity: higher amounts of water between cells in some areas, and a lower density of connections between neurons in others. The areas with higher levels of free water are known to have more glial cells which provide support to neurons. They also have more receptors that bind to fatty acids (which are often raised in people with obesity) and more receptors for molecules and cells involved in the immune response. In contrast, the areas with a lower density of connections between neurons usually were more closely associated with genetic risk factors associated with obesity, and fewer receptors involved in feeding, appetite and energy use. The findings of Kitzblicher et al. suggest that differences in the density of connections between neurons may contribute to obesity. High water content in grey matter, on the other hand, may be a consequence of obesity that occurs as a result of immune receptors becoming activated. This provides new insights in to how obesity and grey matter in the brain are connected.

The Chinese thermal comfort dataset.

Heating and cooling in buildings accounts for over 20% of total energy consumption in China. Therefore, it is essential to understand the thermal requirements of building occupants when establishing building energy codes that would save energy while maintaining occupants' thermal comfort. This paper introduces the Chinese thermal comfort dataset, established by seven participating institutions under the leadership of Xi'an University of Architecture and Technology. The dataset comprises 41,977 sets of data collected from 49 cities across five climate zones in China over the past two decades. The raw data underwent careful quality control procedure, including systematic organization, to ensure its reliability. Each dataset contains environmental parameters, occupants' subjective responses, building information, and personal information. The dataset has been instrumental in the development of indoor thermal environment evaluation standards and energy codes in China. It can also have broader applications, such as contributing to the international thermal comfort dataset, modeling thermal comfort and adaptive behaviors, investigating regional differences in indoor thermal conditions, and examining occupants' thermal comfort responses.

An immersive multisensory virtual reality approach to the study of human-built environment interactions: Technical workflows.

Virtual Reality technology has gained increased attention due to its capacity to provide immersive and interactive experiences to its users. Although increasing evidence has suggested that incorporating multisensory components in VR can promote the sense of presence and improve user performance, most of the current VR applications are limited to visual and auditory senses. In this article, a novel method of integrating thermal-related devices (heat lamps and fans) into Virtual Reality was developed. Automated interaction with the thermal-related devices was achieved using Arduino-based control module with its program embedded into the VR platform-Unity. The functions, hardware and software requirements of the multisensory Virtual Reality system as well as the step-by-step procedures are detailed to provide a reproducible workflow for future applications.•A practical workflow to integrate thermal apparatus into Virtual Reality.•Dynamic airflow and radiative heating incorporated into Virtual Reality.•Automated process to allow user interaction with the thermal components in Virtual Reality.

How many days of indoor positioning system data are required to characterise typical movement behaviours of office workers?

Indoor Positioning Systems (IPS) appear to offer great potential to study the movement and interaction of people and their working environment, including office workplaces. But little is known about appropriate durations for data collection. In this study, location observations collected from 24 office workers on a 1220 m2 office floor over a 3-month period, were analysed to determine how many days are required to estimate their typical movement and spatial behaviours. The analysis showed that up to 8 days of data was sufficient to characterise participants' typical daily movement behaviours and 10 days were required to estimate their typical spatial mobility. However, the results also indicate that 5 weeks of data collection are required to gather the necessary 10 days of data from each participant. These findings will help researchers and workplace professionals to understand the capabilities and requirements of IPS when considering their use in indoor work environments.

The potential for indoor fans to change air conditioning use while maintaining human thermal comfort during hot weather: an analysis of energy demand and associated greenhouse gas emissions.

BACKGROUND: Increasing air conditioner use for cooling indoor spaces has the potential to be a primary driver of global greenhouse gas emissions. Moving indoor air with residential fans can raise the temperature threshold at which air conditioning needs to be turned on to maintain the thermal comfort of building occupants. We investigate whether fans can be used to reduce air conditioner use and associated greenhouse gas emissions. METHODS: We developed an integrated framework, featuring a dynamic adaptive thermal comfort model with a geographical information system-based spatially gridded map of Australia, further complemented with census data. We assessed the change in energy use and associated greenhouse gas emissions for five scenarios of air conditioner and fan use: an air conditioner-only scenario (no fans); and four fan-first scenarios with fans operating at speeds of 0·1 m/s, 0·3 m/s, 0·8 m/s, and 1·2 m/s, with air conditioning used only once the upper temperature threshold for thermal discomfort is exceeded. For each day of the selected case study year, we estimated the upper temperature limit for thermal comfort and the number of hours in which air conditioning would be switched on. FINDINGS: The thermal comfort threshold was increased by the use of fans compared with air conditioner use alone. We found that widespread indoor fan use had the potential to reduce energy demand and greenhouse gas emissions attributable to air conditioner use, without compromising thermal comfort. Taking an annual perspective, the use of fans with air speeds of 1·2 m/s compared with air conditioner use alone resulted in a 76% reduction in energy use (from 5592 GWh to 1344 GWh) and associated greenhouse gas emissions (5091 kilotonnes to 1208 kilotonnes). INTERPRETATION: A common strategy to cope with hot weather is the use of air conditioners, which feed a cycle of high electricity consumption, often delivered by fossil fuel power stations that in turn contribute to further increases in emissions. Moving air with electric fans could serve as a sustainable alternative, reducing air conditioner use and associated greenhouse gas emissions without sacrificing thermal comfort. FUNDING: Australian Research Council, New South Wales Department of Planning, Industry and Environment, and The University of Sydney.

Effect of adaptive opportunity on cognitive performance in warm environments.

This study investigates the hypothesis that thermal adaptive opportunities available to building occupants affect their cognitive performance and mental workload. The change rate of cerebral blood flow (Δtotal Hb) was measured by Near Infra-Red Spectroscopy (NIRS) and interpreted as the metric of mental workload in subjects while performing cognitive tasks (n-back tests) with, or without access to thermal adaptive opportunities such as regulable fan-induced air flow and clothing insulation adjustment. Participants underwent three experimental conditions: Condition 22 (operative temperature to = 22 °C without adaptive opportunities), Condition 28 (to = 28 °C without adaptive opportunities), and Condition 28w (to = 28 °C with adaptive opportunities. Under Condition 28w, thermal sensations were neutral, while thermal satisfaction and comfort levels were higher than those reported for Condition 28, and the same as those reported under Condition 22. The subjects' mean skin temperature under Condition 22 was the lowest at 32.1 °C, followed by Condition 28w at 33.6 °C, while the highest, 34.5 °C was recorded in Condition 28. No significant differences were observed in accuracy and reaction time of n-back tests between the three different environmental conditions. Under Condition 28w, mental fatigue levels and the left side Δ total Hb results were lowest out of all three conditions, although the differences failed to reach statistical significance. Availability of adaptive opportunities plays a role in expanding the range of thermal environmental conditions for optimal cognitive task performance in a moderately warm environment (to = 28 °C). This finding cannot be fully explained by the direct effect of adaptive behaviours on human heat balance and associated physiological responses, but the unexplained component may potentially be attributed to the psychological dimension of human adaptive response. These findings and their interpretation within an adaptive comfort framework are consistent with the extended-U hypothesis of cognitive performance.

A sex/age anomaly in thermal comfort observed in an office worker field study: A menopausal effect?

In a field study conducted in office settings in Sydney, Australia, background survey and right-here-right-now thermal comfort questionnaires were collected from a sample of office workers. Indoor environmental observations, including air temperature, mean radiant temperature, air velocity, and relative humidity, were also recorded and matched with each questionnaire according to the time and location. During exploratory data analyses, we observed that female subjects aged over 40 and 50 or younger registered significantly warmer sensations than other subjects, male and female, from other age ranges. To further explore this phenomenon, the sample of building occupants was classified into two groups-women of perimenopausal age (over 40 and 50 or younger) while the remaining respondents served as a reference group for comparison. Women in the perimenopausal age range demonstrated an increased perception of warmth (p < 0.01) and expressed thermal dissatisfaction more frequently (p < 0.01) than the reference group respondents who were exposed to the same indoor environmental conditions. Furthermore, women of perimenopausal age also expressed preference for cooler thermal environments, that is, lower air temperature (p < 0.01) and greater air movement (p<0.01) than the reference group, and their thermal neutrality (ie, the room temperature corresponding to a neutral thermal sensation) was approximately 2°C cooler than that of the reference group (20.7°C vs 22.4°C). A potential physiological explanation for the distinct thermal perception of women aged over 40 and 50 or younger observed in this study could stem from menopausal symptoms-the presence of hot flushes and dysregulation of the thermoregulatory system.

Activity space, office space: Measuring the spatial movement of office workers.

A key to the development of more effective interventions to promote movement and reduce physical inactivity in office workplaces may be to measure and locate individual's spatial movement. Using an activity space estimation method, high resolution location data collected from 15 office workers over 12 days were used to estimate and analyse the location and extent of their daily spatial movement whilst in an office work-based setting. The results indicated that the method, kernel density estimation, combined with location data offers significant opportunities to not only measure and compare spatial movement behaviours but also simultaneously identify the locations where the behaviours occur. Combined with other data streams, this method will allow researchers to further investigate the influence of different environmental characteristics on these behaviours, potentially leading the development of more effective, longer lasting interventions to promote movement and reduce stationary behaviour, ultimately improving the health of office workers.

Overcooling of offices reveals gender inequity in thermal comfort.

Growth in energy use for indoor cooling tripled between 1990 and 2016 to outpace any other end use in buildings. Part of this energy demand is wasted on excessive cooling of offices, a practice known as overcooling. Overcooling has been attributed to poorly designed or managed air-conditioning systems with thermostats that are often set below recommended comfort temperatures. Prior research has reported lower thermal comfort for women in office buildings, but there is insufficient evidence to explain the reasons for this disparity. We use two large and independent datasets from US buildings to show that office temperatures are less comfortable for women largely due to overcooling. Survey responses show that uncomfortable temperatures are more likely to be cold than hot regardless of season. Crowdsourced data suggests that overcooling is a common problem in warm weather in offices across the US. The associated impacts of this pervasive overcooling on well-being and performance are borne predominantly by women. The problem is likely to increase in the future due to growing demand for cooling in increasingly extreme climates. There is a need to rethink the approach to air-conditioning office buildings in light of this gender inequity caused by overcooling.

Hot weather and heat extremes: health risks.

Hot ambient conditions and associated heat stress can increase mortality and morbidity, as well as increase adverse pregnancy outcomes and negatively affect mental health. High heat stress can also reduce physical work capacity and motor-cognitive performances, with consequences for productivity, and increase the risk of occupational health problems. Almost half of the global population and more than 1 billion workers are exposed to high heat episodes and about a third of all exposed workers have negative health effects. However, excess deaths and many heat-related health risks are preventable, with appropriate heat action plans involving behavioural strategies and biophysical solutions. Extreme heat events are becoming permanent features of summer seasons worldwide, causing many excess deaths. Heat-related morbidity and mortality are projected to increase further as climate change progresses, with greater risk associated with higher degrees of global warming. Particularly in tropical regions, increased warming might mean that physiological limits related to heat tolerance (survival) will be reached regularly and more often in coming decades. Climate change is interacting with other trends, such as population growth and ageing, urbanisation, and socioeconomic development, that can either exacerbate or ameliorate heat-related hazards. Urban temperatures are further enhanced by anthropogenic heat from vehicular transport and heat waste from buildings. Although there is some evidence of adaptation to increasing temperatures in high-income countries, projections of a hotter future suggest that without investment in research and risk management actions, heat-related morbidity and mortality are likely to increase.

Reducing the health effects of hot weather and heat extremes: from personal cooling strategies to green cities.

Heat extremes (ie, heatwaves) already have a serious impact on human health, with ageing, poverty, and chronic illnesses as aggravating factors. As the global community seeks to contend with even hotter weather in the future as a consequence of global climate change, there is a pressing need to better understand the most effective prevention and response measures that can be implemented, particularly in low-resource settings. In this Series paper, we describe how a future reliance on air conditioning is unsustainable and further marginalises the communities most vulnerable to the heat. We then show that a more holistic understanding of the thermal environment at the landscape and urban, building, and individual scales supports the identification of numerous sustainable opportunities to keep people cooler. We summarise the benefits (eg, effectiveness) and limitations of each identified cooling strategy, and recommend optimal interventions for settings such as aged care homes, slums, workplaces, mass gatherings, refugee camps, and playing sport. The integration of this information into well communicated heat action plans with robust surveillance and monitoring is essential for reducing the adverse health consequences of current and future extreme heat.

Predicting thermal pleasure experienced in dynamic environments from simulated cutaneous thermoreceptor activity.

Research into human thermal perception indoors has focused on "neutrality" under steady-state conditions. Recent interest in thermal alliesthesia has highlighted the hedonic dimension of our thermal world that has been largely overlooked by science. Here, we show the activity of sensory neurons can predict thermal pleasure under dynamic exposures. A numerical model of cutaneous thermoreceptors was applied to skin temperature measurements from 12 human subjects. A random forest model trained on simulated thermoreceptor impulses could classify pleasure responses (F1 score of 67%) with low false positives/negatives (4%). Accuracy increased (83%) when excluding the few extreme (dis)pleasure responses. Validation on an independent dataset confirmed model reliability. This is the first empirical demonstration of the relationship between thermoreceptors and pleasure arising from thermal stimuli. Insights into the neurophysiology of thermal perception can enhance the experience of built environments through designs that promote sensory excitation instead of neutrality.

Dynamic thermal pleasure in outdoor environments - temporal alliesthesia.

Thermal comfort research has been historically centred around the concept of "thermal neutrality". Thermal neutrality originates from the steady-state indoor environment and is increasingly questioned when used to define the optimum sensation in outdoor environments. This calls for new criteria, designated for non-steady state and dynamically evolving outdoor settings. To address this need, we investigated thermal pleasure dynamics in outdoor environments based on thermal alliesthesia - a psychophysiological framework for understanding the hedonic responses elicited by non-steady-state thermal exposures. Detailed field studies were conducted in Sydney, Australia, during a 30-day period covering both summer and winter with a total of 35 subjects. The thermal sensation scale was quantitatively divided into four alliesthesial potential areas - two with moderate and two with strong alliesthesial potential - based on their divergence to the preferred sensation. We find that the temporal pleasure change (dP) can be predicted using thermal sensation change (dT). The results showed that linear regression performed strongly (R2 = 0.77 for summer and R2 = 0.79 for winter) in predicting dP when subjects' preceding sensation was in the strong alliesthesial potential zones - namely the 'Hot' and 'Cold' areas. When subjects' prior thermal sensation fell in the thermoneutral zone with moderate alliesthesial potential, a quadratic fit against dT provides a more reasonable prediction of dP (R2 = 0.61 for summer and R2 = 0.56 for winter). The dynamic thermal pleasure models provide a more nuanced subjective interpretation of outdoor urban spaces that includes thermal pleasure and delight. This study contributes further empirical support to the thermal alliesthesia framework and extends its application scope into outdoor thermal comfort research.

Movement at work: A comparison of real time location system, accelerometer and observational data from an office work environment.

Office workers can spend significant periods of time being stationary whilst at work, with potentially serious health consequences. The development of effective health interventions could be aided by a greater understanding of the location and environmental context in which this stationary behaviour occurs. Real time location systems (RTLS) potentially offer the opportunity to gather this much needed information, but they have not been extensively trialled in office workplaces, nor rigorously compared against more familiar devices such as accelerometers. The aim of this paper was to determine whether an RTLS can measure and spatially locate the non-stationary and stationary behaviours of adults working in an office work environment. Data collected from a series of comparison studies undertaken in a commercial office building suggests that RTLS can measure the velocity at which people are moving and locate them, when stationary, with an accuracy of 0.668 m (SD 0.389). This opens up significant opportunities to further understand how people move within buildings, the indoor physical environmental influences on that movement, and the development of effective interventions to help people to move more whilst at work.

Development of a bioclimatic wind rose tool for assessment of comfort wind resources in Sydney, Australia for 2013 and 2030.

This study assessed the effect of wind on human thermal comfort by preforming outdoor urban climatic comfort simulations using state-of-the-art heat-balance models of human thermo-physiology (Universal Thermal Climate Index-UTCI). A series of simulations for computing "wind cooling potential" have been performed using the UTCI index temperatures. The comfort cooling effect of wind has been estimated by modelling with wind taken into account, and under calm wind (0.05 m/s) (ΔUTCI). A novel wind rose biometeorological data visualisation tool that integrates an additional thermal comfort dimension into the conventional climatology wind rose visualisation was developed in this study. The new wind rose graphic tool identifies "predominant" wind directions, and whether or not they are "desirable" from the human thermal comfort point of view. This tool's utility lies in its identification of the optimal building orientation in its surrounding urban morphology, based on the cooling potential of wind resources when enhanced ventilation is desirable for thermal comfort.

Outdoor thermal physiology along human pathways: a study using a wearable measurement system.

An outdoor summer study on thermal physiology along subjects' pathways was conducted in a Japanese city using a unique wearable measurement system that measures all the relevant thermal variables: ambient temperature, humidity, wind speed (U) and short/long-wave radiation (S and L), along with some physio-psychological parameters: skin temperature (T skin), pulse rate, subjective thermal sensation and state of body motion. U, S and L were measured using a globe anemo-radiometer adapted use with pedestrian subjects. The subjects were 26 healthy Japanese adults (14 males, 12 females) ranging from 23 to 74 years in age. Each subject wore a set of instruments that recorded individual microclimate and physiological responses along a designated pedestrian route that traversed various urban textures. The subjects experienced varying thermal environments that could not be represented by fixed-point routine observational data. S fluctuated significantly reflecting the mixture of sunlit/shade distributions within complex urban morphology. U was generally low within urban canyons due to drag by urban obstacles such as buildings but the subjects' movements enhanced convective heat exchanges with the atmosphere, leading to a drop in T skin. The amount of sweating increased as standard effective temperature (SET*) increased. A clear dependence of sweating on gender and body size was found; males sweated more than females; overweight subjects sweated more than standard/underweight subjects. T skin had a linear relationship with SET* and a similarly clear dependence on gender and body size differences. T skin of the higher-sweating groups was lower than that of the lower-sweating groups, reflecting differences in evaporative cooling by perspiration.

Microrheological investigations in ionic liquids using optical trapping techniques.

In this paper, we demonstrate optical trapping of melamine particles (d ≈ 2.3 µm) within the pure ionic liquid ethylammonium nitrate (EAN) and show the first microrheological investigations of these important compounds using this technique. By analyzing the power spectrum of a particle trapped in EAN, we monitor the variation in viscous drag that it experiences in proximity to the sample coverslip, showing excellent agreement with Faxén's law. We also demonstrate hydrodynamic coupling between pairs of trapped particles. Finally, we explore temperature-dependent viscosity changes in ∼µL samples of EAN as a further example of microrheological investigations of ILs.

Single aerosol trapping with an annular beam: improved particle localisation.

In this paper we explore the trapping of aerosol droplets using an annular beam, formed by blocking the central portion of a Gaussian beam, and quantify the improvements over conventional Gaussian beam traps. Recent work on the modelling of single aerosol dynamics within an optical tweezer trap [Burnham et al., Journal of the Optical Society of America B, 2011, 28, 2856-2864] has indicated that the use of annular beams can allow smaller droplets to be trapped, which we experimentally verify. We also demonstrate that annular beams allow droplets to be trapped at higher powers, and with reduced axial displacement with increasing power, than Gaussian beams. We confirm these results, due to a reduction in the axial scattering forces, using this theoretical model. Finally back focal plane interferometry is used to determine the axial and lateral trap stiffnesses for a series of droplets, showing a significant increase in the axial : lateral trap stiffness ratio from 0.79 ± 0.04 to 1.15 ± 0.04 when an annular beam is used.