Clinical Research Directory

Title: ICARUS - Psycho-physiological Profiling of Low and High Heat-resilient Individuals

The escalating environmental heat-stress associated with global warming is a societal challenge with large and potential harmful consequences for humans. Excess morbidity and mortality during heat waves provides strong evidence for fatal outcomes. However, it is unclear why some people are particularly vulnerable and get sick from hyperthermia, while others adapt and tolerate exposure. The Icarus project aims to provide a psycho-physiological framework for improved mitigation of the health threats associated with global warming. Combining expertise in integrative thermal physiology, pharmacology, photobiology, psychology and machine learning, we will collaborate on comprehensive cross-scientific studies using controlled lab-exposure combined with investigations in ecological settings including vulnerable and highly tolerant people across populations from northern to southern Europe. Advanced algorithms will be developed to generate personalized alerts and advising based on behavioral patterns, psychological profiling, predicted vulnerability and willingness to adopt resilience-building strategies. Global warming is projected to continue towards the end of the 21st century and constitutes an increasing threat to human health unless we as individuals and collectively become better in preventing acute effects, as well as devise sustainable strategies to limit further anthropogenic warming of the climate system. Acutely, improved guidance is important for both individual and public health, where Icarus aims at providing a highly improved basis for preventing heat-related disease, advising or nudging people towards pro-health behavior, including smarter use of technologies to mitigate heat stress, or adjusting medication to reduce adverse effects during heat events. In support of the sustainability agenda, our framework also forms a novel basis for developing advising algorithms relevant for optimization of climate change mitigation policy-making.

Indigenous Nutritional Supplements for Pregnancy to Improve Resilience in Environmental Heat

The purpose of this study is to learn whether a simple, traditional, and balanced meal made from local foods, eaten once a day during pregnancy, can help women in rural Pakistan stay healthier in hot weather and give birth to healthier babies. Climate change has made heat a serious challenge for pregnant women, especially in areas with limited resources. This study will explore whether an indigenous meal that is culturally acceptable and easy to prepare can improve resilience to heat stress and support better outcomes for both mothers and newborns. The study will focus on two main questions: * Can this daily balanced meal reduce the harmful effects of heat stress during pregnancy? * Does it improve newborn health, especially birth weight? Researchers will compare women who eat the balanced local meal every day with women who continue their usual meals. They will check changes in women's health, levels of key vitamins and nutrients, and their babies' birth outcomes. During the study, participants will: * Either eat the balanced local meal daily or continue their usual meals. * Share information on their health, diet, and heat exposure. * Provide small samples, such as blood and stool, to study nutrient levels and gut health. * Have their newborns' health and growth measured at birth.

Heat Stress Exposure Among Low-Income Residents in Bangladesh and Evaluation of Indoor Interventions

The goal of this clinical trial is to learn if infrastructure and equipment installed to cool homes reduce adverse health outcomes. The main questions it aims to answer are: What is the impact of the intervention on indoor heat stress? What is the impact of the intervention on personal exposure to heat stress? What is the impact of the intervention on health outcomes, including heart rate, and heart rate variability, and sleep quality? Participants will have cooling infrastructure and/or equipment installed in their home; have heat stress sensors installed inside and outside their home and wear personal heat stress monitors; allow some biological functions such as heat rate, heat rate variability, and sleep quality.

Implementing an Intervention to Reduce Heat Stress and Chemical Exposures

The investigators are studying the dangers that farmworkers face while working in the fields and at home. The investigators goals are: 1. Measure how much heat and chemicals farmworkers in Imperial County are exposed to. The investigators will ask the participants to wear a special belt under their clothes during work to measure heat. The investigators will also put two small temperature monitors in the participant's home for a day. The investigators will collect a urine sample to check hydration, and also measure the participants height, weight, blood pressure, and some blood markers for diseases using a simple finger-prick test. To measure chemicals, the investigators will give the participants a wristband to wear for a week and hang another in the participants home. The investigators will also collect dust from each participant's home with a vacuum. Then, the investigators will analyze everything at San Diego State University. After collecting samples, a trained community health worker will ask the participants a few questions about their work, lifestyle, health symptoms, and any hazards they face. The investigators will meet the participants twice at their homes to distribute the tools which will later be collected. Once the tools are collected, the investigators will have the chance to follow up with the participants if they have any questions. 2. Provide help to lower heat and chemical exposure with the help of community health workers. 3. Measure heat and chemicals again using the same methods to see if the project made a difference. 4. Talk to participants about what they liked and how the investigators can make future projects better.

Impact of Indoor Overheating on Physiological Strain in Children

Communities worldwide are experiencing increasing heat extremes that challenge the limits of human thermoregulation, particularly among vulnerable populations such as children. Compared with adults, children are more susceptible to heat related illness due to less efficient thermoregulatory systems and difficulty recognizing early signs of heat stress. In addition, prolonged heat exposure can adversely affect their mental health, contributing to cognitive decline, heightened anxiety, and irritability. As children spend substantial time in hot environments at school and at home, and as these conditions intensify with climate change, actions to safeguard their health are essential. Yet our understanding of heat exposure effects in children remains incomplete, hindering the development of evidence based strategies to protect them. To address this gap, the investigators aim to evaluate whether an indoor temperature limit of 26 °C (45 percent relative humidity), the upper threshold recommended to protect older adults, can effectively prevent dangerous increases in physiological strain and declines in cognitive function in children during a simulated daylong heatwave. The preliminary study will assess physiological and cognitive responses in children aged 10 to 15 years during a 6 hour exposure (approximating a typical school day) to two conditions: (1) the recommended indoor temperature upper limit (26 °C) and (2) a high heat condition representative of homes and schools without air conditioning during extreme heat events (36 °C). In both conditions, children will remain seated at rest while wearing light clothing (t shirt and shorts), with the exception of performing 15 minutes of stepping exercise (6-6.5 METS) each hour (excluding the lunch period) to reflect typical daily activity in a school setting. This experimental design will allow investigators to determine whether maintaining indoor temperatures at the recommended upper limit for older adults sufficiently mitigates physiological strain in children.

Heat Stress in Individuals With Schizophrenia

Schizophrenia is a severe mental illness affecting approximately 24 million people worldwide and is associated with more than double the all cause mortality risk of the general population. Emerging evidence demonstrates that elevated temperatures acutely worsen mental health symptoms and significantly increase the risk of heat related morbidity and mortality. For people living with schizophrenia, prolonged exposure to heat can exacerbate psychiatric symptoms, impair judgment and decision making, and reduce the ability to engage in protective behaviors such as increasing hydration, reducing clothing, improving ventilation, or seeking cooler environments. As a result, individuals with schizophrenia may experience higher rates of heat related illness. To date our understanding of heat exposure effects in individuals with schizophrenia remains incomplete, hindering the development of evidence-based strategies to protect them. Thus, the primary objective of this exploratory study is to gather preliminary data on the effects of indoor overheating on physiological responses (core body temperature and cardiovascular function), cognitive performance (attention, working memory, and reaction time), and mood in adults with schizophrenia. Specifically, we will assess whether maintaining indoor conditions at the upper recommended temperature limit for older adults (26°C, 45% relative humidity \[RH\]; PMID: 38329752) is sufficient to mitigate physiological strain compared with exposure to a hot indoor environment (36°C, 45% RH) representative of non-air-conditioned homes during extreme heat events in individuals with schizophrenia. In both conditions, the individual will remain seated at rest while wearing light clothing (t shirt and shorts), with the exception of performing 15 minutes of stepping exercise (4-4.5 METS) each hour (excluding the lunch period) to reflect typical daily activities of daily living.

Beat the Heat Boston

The goal of this stepped wedge trial is to assess the practical effects of air conditioners on hot weather impacts among older adults. The main questions it aims to answer are: How does the presence of an air conditioning unit affect heat stress, heat strain, mental health, and healthcare utilization among older adults who did not previously have access to air conditioning? How, and in what conditioners, do older adults use air conditioning once it is installed in their home? Researchers will compare participants in arms with (A) and without (B) air conditioning units in the first summer season; this will allow them to assess the effect of air conditioners. In the second summer season, both arms will have air conditioning units, but those in the year two distribution arm (B) will receive an electricity subsidy, while those in the year one AC distribution arm (A) will not, allowing researchers to assess the effect of an electricity subsidy. Participants will be randomized to receive an air conditioner and financial support for electricity costs in either the first summer season or the second summer season of the study. * Heat stress, heat strain, mental health, and healthcare utilization will be assessed via participant survey. * Air conditioner utilization will be assessed via continuous load monitoring devices. * Indoor air temperature will be assessed via continuous data loggers.

Suitability of a 26 °C Indoor Environment for Mitigating Heat Strain in Young Adults

While an indoor upper temperature limit of 26 °C has been shown to protect heat-vulnerable older adults (DOI: 10.1289/EHP11651), this guideline has not been verified in young, habitually active adults. Public health recommendations during hot weather typically emphasize staying in cool environments, avoiding strenuous activity, wearing lightweight clothing, and maintaining adequate hydration. However, young adults may be less likely to follow these guidelines. They often do not reduce their physical activity during extreme heat events and may overdress for fashion, cultural, or religious reasons. These behaviors can impose an additional thermoregulatory burden and lead to greater physiological strain during heat exposure, even though young adults generally have a higher capacity for heat dissipation than older individuals. Accordingly, it is important to evaluate whether an indoor temperature limit of 26 °C is sufficient to protect young, habitually active adults. To address this gap, the investigators aim to assess changes in body temperature and cardiovascular strain in young, habitually active adults (18-29 years) during an 8-hour exposure to the recommended indoor upper temperature limit of 26 °C and 45% relative humidity (humidex of 29, considered comfortable). Participants will complete two conditions: A) seated rest while dressed in light clothing (T-shirt, shorts, and socks), and B) light exercise (stepping to simulate activities of daily living, 4-4.5 METs) performed once per hour (except for the lunch hour) while dressed in light clothing plus an additional insulating layer (sweatshirt and sweatpants). This experimental design will allow investigators to determine the effects of added clothing insulation and light activity-representative of typical daily behaviors-on physiological strain in young adults, and to assess whether refinements to the recommended 26 °C indoor temperature limit are warranted for this population.

Identifying the Limits of Survivability in Heat-exposed Older Females

Climate change increases extreme heat events, elevating global heat-illness risk. Females have reduced heat loss capacity (\~5%) compared to males, driven by differences in skin blood flow and sweating responses. While findings on sex-mediated mortality are mixed, some studies suggest older females (≥65 years), face higher heat-related mortality/morbidity risks, evidenced by disproportionate female deaths in the 2021 Western Heat Dome. The effects of extreme uncompensable heat on older females remain understudied. Heat exposure initially causes net heat gain, raising core/skin temperatures and triggering heat-loss responses. Under compensable heat stress, heat loss balances gain, stabilizing core temperature. Uncompensable heat stress (exceeding maximal dissipation capacity) causes continuous core temperature rise, posing severe health risks. The specific temperature and relative humidity (RH) limits where compensability is lost are critical survival determinants, influenced by age and sex. Ramping protocols identify these limits: participants face progressively increasing heat stress (e.g., staged humidity rises) while core temperature is monitored. Core temperature typically stabilizes initially, then exhibits an abrupt rapid increase at an inflection point, operationally defined as the limit of compensability. Despite increasing use, ramping protocol validity for accurately identifying this threshold remains unverified. This project assesses ramping protocol validity for determining uncompensable conditions in older females and evaluates cumulative thermal and cardiovascular strain, as well as psychological and cognitive responses to both uncompensable and compensable heat. Participants will complete five trials. Trial 1 (Ramping): Rest at 42°C, 28% RH for 70min, then incremental RH increases (3% every 10min) to 70% RH. Individual core temperature (rectal) inflection points are identified from the ramping trial. Trials 2-5 (Fixed Conditions, Randomized): i) \~10% below inflection; ii) \~5% below inflection; iii) \~5% above inflection; iv) Thermo-neutral control (26°C, 45% RH). Comparing the rate of rectal temperature change and cumulative strain during prolonged fixed exposures (especially below vs. above inflection) will validate if the ramping inflection point represents the true limit of compensability for older females.

Suitability of the 26 °C Indoor Temperature Upper Limit for Older Adults: Impacts of Clothing and Daily Activity

While an upper limit of 26°C has been shown to be protective for heat-vulnerable older occupants (DOI: 10.1289/EHP11651), this recommendation did not consider the added heat burden associated with increases in internal heat production accompanying activities of daily living or the restriction to heat loss caused by clothing insulation. To safeguard the health of older adults, health agencies worldwide recommend the remain in cool space indoors, avoid strenuous activity, wear lightweight clothing, and drink cool water regularly throughout the day. However, older adults do not sense heat as well as their younger counterparts. Consequently, they may not take appropriate countermeasures to mitigate physiological strain from indoor overheating. This may include overdressing despite high indoor temperatures. In other cases, individuals may wear insulated clothing in hot weather to observe cultural or religious modesty requirements, which serve as expressions of faith and identity rather than a tool for thermoregulation. Further, individuals may be unaware of the consequences of increases in physical activity on heat gain and may therefore not adjust their normal day-to-day activity levels to prevent potentially dangerous rises in body temperature. Consequently, this may necessitate a lowering of recommended upper indoor temperature limit during hot weather. To address these important considerations, on separate occasions the investigators will assess the change in body temperature and cardiovascular strain in older adults (65-85 years) exposed for 8 hours to the recommended indoor temperature upper limit of 26°C and 45% relative humidity equivalent humidex of 29 (considered comfortable) while they A) perform seated rest dressed in light clothing (t-shirt, shorts and socks), B) perform light exercise (stepping exercise to simulate activities of daily living, 4-4.5 METS) every hour (except during lunch hour period) dressed in light clothing, C) perform light exercise (4-4.5 METS) every hour (except during lunch hour period) dressed in light clothing (t-shirt, shorts and socks) and an added clothing layer (sweatshirt and sweatpants) and D) perform seated rest dressed in light clothing (t-shirt, shorts and socks) and an added clothing layer (sweatshirt and sweatpants). With this experimental design, investigators will assess the effects of added clothing insulation and light activity, representative in activities of daily living on physiological strain and identify whether refinements in the recommended 26°C indoor temperature limit may be required.

Aging, Beta Blockers, and Thermoregulatory Responses

This study will test the hypothesis that the drugs propranolol and metoprolol will result in greater increases in core body temperature during 3 hours of extreme heat exposure in older adults.

The Impact of Wearing the Hijab on Whole-body Heat Loss During Exercise-heat Stress

The hijab (headscarf and cloak) is a Muslim dress, which covers the head, neck and chest, and conceals the female hair, leaving the face uncovered. It is worn by Muslim women worldwide including young Muslim women engaging in sports and exercise. As with any clothing worn on the body, the hijab can impact heat dissipation during exercise, potentially leading to increased body temperature and discomfort, especially in warmer environments. However, the extent to which the hijab may restrict heat loss remains unclear. This study aims to assess dry and evaporative heat exchange in young women performing moderate-intensity intermittent exercise in dry heat conditions (40°C, 15% relative humidity).

Influence of Indoor Humidity on Physiological Strain in Older Adults During a Simulated Heat Wave

Laboratory-based studies show that exposure to high humidity can worsen the effects of heat stress in young and older adults by impeding sweat evaporation - the main mechanism by which the human body cools itself. At high levels of humidity, the efficiency of sweating decreases causing a greater rise core temperature and burden on the cardiovascular system. In this context, increasing temperatures and humidity with climate change thus pose a potential compound risk for human health. While humidity's role in heat-health outcomes could substantially alter projections of health burdens from climate change, the impact of humidity on physiological strain in vulnerable people in relation to the indoor environment has yet to be evaluated. In a recent study delineating the physiological effects of the proposed 26°C indoor upper limit (PMID: 38329752), relative humidity was set to 45% in all conditions based on indoor humidity standards by the American Society of Heating and Air-Conditioning Engineers. However, it is unknown whether a refinement of the recommended indoor temperature limit of 26°C is required in situations where humidity cannot be maintained at this level. On separate occasions, the investigators will assess the change in body temperature and cardiovascular strain in older adults (65-85 years) exposed for 10 hours at the recommended indoor temperature limit of 26°C and 45% relative humidity (equivalent humidex of 29 (considered comfortable)) (experimental condition A), to 26°C with a relative humidity of 15% (equivalent humidex of 23 (considered comfortable); humidex is used to measure the perceived temperature taking into account the humidity)) (experimental condition B), to 26°C with a relative humidity of 85% (equivalent humidex of 37 (considered somewhat uncomfortable)) (experimental condition C), and to 31°C and 45% relative humidity with an equivalent humidex of 37 (considered somewhat uncomfortable) that is similar to experimental condition C. With this experimental design, investigators will assess the effects of indoor humidity in driving human heat strain and identify whether refinements in the recommended 26°C indoor temperature limit may be required. Further, by evaluating changes in relation to ambient conditions with a similar humidex, the investigators can assess how individuals perceive and respond to both heat and humidity.

Ethanol Consumption in the Heat

Climate change has significantly increased the earth's average surface temperature and heat waves have been predicted to increase in frequency, intensity and duration. Extreme heat events have increased the susceptibility to heat-related illnesses, such as heat exhaustion, heat stroke or death. Heat health action plans have been designed to advertise cooling behaviours to mitigate physiological strain. Heat health action plans suggest avoiding alcohol consumption during extreme heat as it may increase dehydration and impair behavioural or physiological temperature regulation and thermal perception. Regardless of these messages, alcohol sales continue to remain high during the summer months year after year, and 1/5 of adults identify alcohol as a hydration strategy during extreme heat events. A recent scoping review investigating the effects of alcohol and heat has demonstrated that acute alcohol consumption does not negatively influence thermoregulation, hydration, or hormone markers of fluid balance in the heat compared to a control fluid (https://doi.org/10.1186/s12940-024-01113-y). Further, alcohol consumption may elicit sex- and age-specific alterations in physiological and perceptual responses, neither of which have been explored. Therefore, this study aims to comprehensively evaluate how alcohol consumption systematically alters physiological responses and perceptions during conditions similar to those experienced indoors during extreme heat events in younger and older adults.

Impact of Extreme Heat on Myocardial Blood Flow and Flow Reserve in Young and Older Adults

Extreme heat causes a disproportionate number of hospitalizations and deaths in older adults relative to any other age group. Importantly, many hospitalizations and deaths are primarily due to cardiovascular events such as myocardial infarction. Previous data indicate that older adults have attenuated skin blood flow and sweating responses when exposed to heat, resulting greater increase in core body temperature. Despite these observations, relatively little is known about the risk for myocardial ischemia potentially contributing to the aforementioned higher morbidity and mortality in older adults during heat waves. The broad objective of this work is to determine the impact of ambient heat exposure on myocardial blood flow and flow reserve in young and older adults. Aim 1 will test the hypothesis that older adults exhibit attenuated myocardial flow reserve compared to young adults during heat stress. Aim 2 will determine if the percent of maximal myocardial flow reserve (assess via vasodilator stress) during heat exposure is higher in older adults compared to young adults. The expected outcome from this body of work will improve our understanding of the consequences of aging on cardiovascular responses to ambient heat stress.

Preparing for Heat Waves - Enhancing Human Thermophysiological Resilience

As the ongoing progression of climate change exposes individuals to elevated temperatures and an escalating frequency of extreme heat events, the risk of more intense and prolonged heat waves raises significant concerns for public health, particularly among vulnerable populations. The physiological response to acute heat stress involves involuntary thermolytic reactions that may strain the cardiovascular system, especially in individuals with pre-existing vulnerabilities. Heat acclimation has been identified as a potential strategy to enhance thermoregulation and mitigate the adverse effects of heat stress. While existing research primarily focuses on athletes and military, this study aims to investigate the impact of a practical heat acclimation strategy, combining passive and active heat exposure, on thermophysiological, cardiovascular and metabolic parameters in healthy overweight adults. The study targets a population at increased risk for heat-related complications, seeking to provide realistic guidelines for broader application when a heat wave appears on the weather forecast.