Deep Learning-based Segmentation of CT Scans Predicts Disease Progression and Mortality in IPF.

RATIONALE: Despite evidence demonstrating a prognostic role for CT scans in IPF, image-based biomarkers are not routinely used in clinical practice or trials. OBJECTIVES: Develop automated imaging biomarkers using deep learning based segmentation of CT scans. METHODS: We developed segmentation processes for four anatomical biomarkers which were applied to a unique cohort of treatment-naive IPF patients enrolled in the PROFILE study and tested against a further UK cohort. The relationship between CT biomarkers, lung function, disease progression and mortality were assessed. MEASUREMENTS AND MAIN RESULTS: Data was analysed from 446 PROFILE patients. Median follow-up was 39.1 months (IQR 18.1-66.4) with cumulative incidence of death of 277 over 5 years (62.1%). Segmentation was successful on 97.8% of all scans, across multiple imaging vendors at slice thicknesses 0.5-5mm. Of 4 segmentations, lung volume showed strongest correlation with FVC (r=0.82, p<0.001). Lung, vascular and fibrosis volumes were consistently associated across cohorts with differential five-year survival, which persisted after adjustment for baseline GAP score. Lower lung volume (HR 0.98, CI 0.96-0.99, p=0.001), increased vascular volume (HR 1.30, CI 1.12-1.51, p=0.001) and increased fibrosis volume (HR 1.17, CI 1.12-1.22, p=<0.001) were associated with reduced two-year progression-free survival in the pooled PROFILE cohort. Longitudinally, decreasing lung volume (HR 3.41; 95% CI 1.36-8.54; p=0.009) and increasing fibrosis volume (HR 2.23; 95% CI 1.22-4.08; p=0.009) were associated with differential survival. CONCLUSIONS: Automated models can rapidly segment IPF CT scans, providing prognostic near and long-term information, which could be used in routine clinical practice or as key trial endpoints. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

Functional respiratory imaging identifies redistribution of pulmonary blood flow in patients with COVID-19.

An increasing observation is that some patients with COVID-19 have normal lung compliance but significant hypoxaemia different from typical acute respiratory distress syndrome (ARDS). We hypothesised that changes in pulmonary blood distribution may be partially responsible and used functional respiratory imaging on CT scans to calculate pulmonary blood volume. We found that patients with COVID-19 had significantly reduced blood volume in the smaller calibre blood vessels (here defined as <5 mm2 cross-sectional area) compared with matched ARDS patients and healthy controls. This suggests that using high levels of PEEP may not alone be enough to oxygenate these patients and that additional management strategies may be needed.

Caffeine and energy drink use by combat arms soldiers in Afghanistan as a countermeasure for sleep loss and high operational demands.

OBJECTIVES: Combat deployments are characterized by high operational demands with limited opportunities for sleep leading to fatigue and degraded cognitive and operational performance. Caffeine in moderate doses is recognized as an effective intervention for physical and cognitive decrements associated with sleep loss. METHODS: This report is based on data collected by two separate, independently conducted surveys administered in Afghanistan in 2011-2012. It assessed caffeine use and sleep disruption among U.S. Army combat soldiers (J-MHAT 8; n = 518) and among deployed soldiers with different military assignments (USARIEM Deployment Survey; n = 260). RESULTS: Daily caffeine intake assessed in the J-MHAT 8 survey averaged 404 ± 18 mg. In the USARIEM Deployment Survey, intake was 303 ± 29 mg and was significantly higher among combat arms soldiers (483 ± 100 mg) compared to combat service support personnel (235 ± 23 mg). In both surveys, over 55% of total caffeine intake was from energy drinks. Additional sources of caffeine included coffee, tea, sodas, gum, candy, and over-the-counter medications. Higher caffeine intake was not associated with ability to fall asleep at night or wake-up in the morning (J-MHAT 8 survey). Higher caffeine consumption was associated with disrupted sleep from high operational tempo and nighttime duties of combat operations. DISCUSSION: Overall caffeine consumption and energy drink use in Afghanistan was greater than among non-deployed soldiers and civilians. Caffeine was frequently used as a countermeasure during night operations to offset adverse effects of sleep loss on physical and cognitive function, consistent with current Department of the Army recommendations.

Inflammatory responses of older firefighters to intermittent exercise in the heat.

PURPOSE: Repeated strenuous work in the heat may predispose firefighters to augmented immune responses and inflammation. This study examined the immune responses in 12 older Firefighters (FF) and 12 older Non-Firefighters (Non-FF), and a group of 6 young FF and 6 young Non-FF, following intermittent exercise in the heat. METHODS: The participants, matched for age, body surface area, body composition, and VO(2peak), cycled 4 × 15 min at moderate-to-high heat production (400 W), each followed by 15-min rest, in dry [10-20% relative humidity (RH)] and humid (60% RH) heat (35 °C). Rectal temperature (T(re)) and heart rate (HR) were measured continuously, and blood samples at baseline (PRE) and following 60-min recovery (POST) were analyzed for Interleukin (IL)-6, Tumor Necrosis Factor (TNF-α), C-reactive protein (CRP), platelet count (PLT), and mean platelet volume (MPV). RESULTS: No differences were observed for T(re), HR, TNF-α, CRP, or PLT between the FF and Non-FF in either condition. The Non-FF had greater changes in IL-6 (Warm/Dry = +1.10 ± 0.18, Warm/Humid = +2.94 ± 0.74 pg mL(-1)), compared to the FF (Warm/Dry = +0.67 ± 0.17, Warm/Humid = +0.70 ± 0.33 pg mL(-1)), and MPV at PRE/POST compared to the FF. Between the young and older FF and Non-FF, no differences in T(re), HR, PLT, or MPV were observed, however, elevated CRP (Warm/Dry) in the older FF, and IL-6 (Warm/Dry) and TNF-α (both conditions) in the older Non-FF, were observed. CONCLUSIONS: The elevated IL-6 in the Non-FF is potentially indicative of increased strain in the Non-FF and/or adaptive changes in the FF due to the occupational demands.

Moderate-intensity intermittent work in the heat results in similar low-level dehydration in young and older males.

Older individuals may be more susceptible to the negative thermal and cardiovascular consequences of dehydration during intermittent work in the heat. This study examined the hydration, thermal, and cardiovascular responses to intermittent exercise in the heat in 14 Young (Y, Mean ± SE; 25.8 ± 0.8 years), Middle-age (MA, 43.6 ± 0.9 years), and Older (O, 57.2 ± 1.5 years) healthy, non-heat acclimated males matched for height, mass, body surface area, and percent body fat. Rectal temperature (Tre), heart rate (HR), local sweat rate (LSR), and hydration indices were measured during 4 × 15-min moderate to heavy cycling bouts at 400 W heat production, each followed by a 15-min rest period, in Warm/Dry (35°C, 20% relative humidity [RH]) and Warm/Humid (35°C, 60% RH) heat. No differences were observed between the age groups for Tre, Tre change, HR, LSR, mass change, urine specific gravity, and plasma protein concentration in either condition, irrespective of the greater level of thermal and cardiovascular strain experienced in the Warm/Humid environment. Plasma volume changes (Dry Y: -5.4 ± 0.7, MA: -6.2 ± 0.9, O: -5.7 ± 0.9%, Humid Y: -7.3 ± 1.0, MA: -7.9 ± 0.8, O: -8.4 ± 1.0%) were similar between groups, as were urine specific gravity and plasma protein concentrations. Thus, physically active Young, Middle-age, and Older males demonstrate similar hydration, thermal, and cardiovascular responses during moderate- to high-intensity intermittent exercise in the heat.

Protein supplementation for military personnel: a review of the mechanisms and performance outcomes.

Protein supplement use is common among athletes, active adults, and military personnel. This review provides a summary of the evidence base that either supports or refutes the ergogenic effects associated with different mechanisms that have been proposed to support protein supplementation. It was clear that if carbohydrate delivery was optimal either during or after an acute bout of exercise that additional protein will not increase exercise capacity. Evidence was also weak to substantiate use of protein supplements to slow the increase in brain serotonin and onset of central fatigue. It was also evident that additional research is warranted to test whether the benefits of protein supplements for enhancing recovery of fluid balance after exercise will affect subsequent work in the heat. In contrast, with repeated exercise, use of protein supplementation was associated with reductions in muscle soreness and often a faster recovery of muscle function due to reductions in protein degradation. There was also good supportive evidence for long-term benefits of protein supplementation for gains in muscle mass and strength through accelerated rates of protein synthesis, as long as the training stimulus was of sufficient intensity, frequency, and duration. However, studies have not examined the impact of protein supplements under the combined stress of a military environment that includes repeated bouts of exercise with little opportunity for feeding and recovery, lack of sleep, and exposure to extreme environments. Both additional laboratory and field research is warranted to help provide evidence-based guidance for the choice of protein supplements to enhance soldier performance.

Do older firefighters show long-term adaptations to work in the heat?

Older experienced firefighters may show signs of heat adaptation, and thus reduced physiological strain, due to repeated occupational heat stress exposure. The aim was to examine physiological and perceptual strain, and hydration, responses to intermittent exercise in the heat in 12 older Non-Firefighter (Non-FF) and experienced Firefighter (FF) males, pair matched for age (Group mean ± SE: Non-FF = 51.7 ± 1.5, FF = 49.8 ± 1.1 years), VO(2peak) (Non-FF = 39.4 ± 2.2, FF = 40.7 ± 1.8 mL·kg(-1)·min(-1)), body surface area (Non-FF = 1.94 ± 0.04, FF = 2.03 ± 0.03 m(2)), and percent body fat (Non-FF = 24.4 ± 2.3, FF = 19.3 ± 1.8%). Rectal (Tre) and mean skin (MT(sk)) temperatures, heart rate (HR), local sweat rate (LSR), hydration indices, and ratings of thermal sensation and perceived exertion were measured during 4 ×15-min (rest 15-min) moderate-to-heavy cycling bouts (400 W heat production) in Dry and Humid heat (35°C, ∼20 and ∼60% relative humidity, respectively). No differences were observed between the Non-FF and FF for T(re), T(re) change, MT(sk), HR,% max HR, LSR, physiological strain index (PhSI), or % plasma volume change. Plasma protein concentration was reduced at baseline for the Non-FF (7.6 ± 0.1 g·100 mL(-1)) than FF (8.0 ± 0.1 g·100 mL(-1)). The Perceptual Strain Index overestimated PhSI for Non-FF and FF in both thermal conditions. At the end of exercise, the Non-FF showed a greater Tre difference between thermal conditions (0.27 ± 0.05°C) compared to the FF (0.10 ± 0.09°C). Although the Non-Firefighters and Firefighters demonstrate similar cardiovascular and hydration responses during moderate-to-heavy intensity exercise within each of the thermal conditions, the attenuated thermal effects between the two heat stress conditions in the Firefighters suggests a protective adaptation.

Physiological strain of next generation combat uniforms with chemical and biological protection: importance of clothing vents.

This study examined whether vents in the arms, legs and chest of new protective assault uniforms (PTAU) reduced heat strain at 35 °C during a low dressed state (DSlow), and subsequently improved tolerance time (TT) after transitioning to DShigh compared with the battle dress uniform and overgarment (BDU+O). Small but significant reductions in rectal temperature (Tre), heart rate and vapour pressures over the thigh and shin were observed during DSlow with vents open (37.9 ± 0.2 °C, 120 ± 10 b/min, 3.7 ± 0.4 and 3.5 ± 1.0 kPa) versus closed (38.0 ± 0.1 °C, 127 ± 5 b/min, 4.3 ± 0.3 and 4.6 ± 0.5 kPa). During DShigh Tre was reduced and TT increased significantly with the PTAUs (1.1 ± 0.2 °C/h and 46 ± 24 min) versus BDU+O (1.6 ± 0.2 °C/h and 33 ± 16 min). The vents marginally reduced heat strain during DSlow and extended TT during DShigh) compared with BDU+O. Practitioner Summary: Clothing vents in chemical and biological protective uniforms can assist with heat transfer in situations where the uniforms must be worn for extended periods prior to exposure to a hazardous condition. Once the vents are closed, exposure time is increased and the increase in body temperature reduced.

Peripheral markers of central fatigue in trained and untrained during uncompensable heat stress.

The development of fatigue is more pronounced in the heat than thermoneutral environments; however, it is unclear whether biomarkers of central fatigue are consistent with the higher core temperature (T (c)) tolerated by endurance trained (TR) versus untrained (UT) during exertional heat stress (EHS). The purpose of this study was to examine the indicators of central fatigue during EHS in TR versus UT. Twelve TR and 11 UT males (mean ± SE [Formula: see text] = 70 ± 2 and 50 ± 1 mL kg LBM(-1) min(-1), respectively) walked on a treadmill to exhaustion (EXH) in 40°C (dry) wearing protective clothing. Venous blood was obtained at PRE and 0.5°C T (c) increments from 38 to 40°C/EXH. Free tryptophan (f-TRP) decreased dramatically at 39.5°C for the TR. Branch chain amino acids decreased with T (c) and were greater for UT than TR at EXH. Tyrosine and phenylalanine remained unchanged. Serum S100ß was undetectable (<5 pg mL(-1)). Albumin was greater for the UT from PRE to 39.0°C and at EXH. Prolactin (PRL) responded to relative thermal strain with similar EXH values despite higher T (c) tolerated for TR (39.7 ± 0.09°C) than UT (39.0 ± 0.09°C). The high EXH PRL values for both groups support its use as a biomarker of the serotonin and dopamine interplay within the brain during the development of central fatigue.

Cortisol and interleukin-6 responses during intermittent exercise in two different hot environments with equivalent WBGT.

Blood marker concentrations such as cortisol (COR) and interleukin (IL)-6 are commonly used to evaluate the physiological strain associated with work in the heat. It is unclear, however, if hot environments of an equivalent thermal stress, as defined by a similar wet bulb globe temperature (WBGT), result in similar response patterns. This study examined markers of neuroendocrine (COR) and immune (IL-6) responses, as well as the cardiovascular and thermal responses, relative to changes in body heat content measured by whole-body direct calorimetry during work in two different hot environments with equivalent WBGT. Eight males performed a 2-hr heavy intermittent exercise protocol (six 15-min bouts of cycling at a constant rate of metabolic heat production (360W) interspersed by 5-min rest periods) in Hot/Dry (46°C, 10% relative humidity [RH]) and Warm/Humid (33°C, 60% RH) conditions (WBGT ∼ 29°C). Whole-body evaporative and dry heat exchange, change in body heat content (ΔH(b)), rectal temperature (T(re)), and heart rate were measured continuously. Venous blood was obtained at rest (PRE) and the end of each exercise bout for the measurement of changes in plasma volume (PV), plasma protein (an estimate of plasma water changes), COR, and IL-6. Ratings of perceived exertion and thermal sensation were measured during the last minute of each exercise bout. No differences existed for ΔH(b), heart rate, T(re),%ΔPV, plasma protein concentration, perceptual strain (thermal sensation, perceived exertion), and COR between the Hot/Dry and Warm/Humid conditions. IL-6 exhibited an interaction effect (p = 0.041), such that greater increases were observed in the Hot/Dry (Δ = 1.61 pg·mL(-1)) compared with the Warm/Humid (Δ = 0.64 pg·mL(-1)) environment. These findings indicate that work performed in two different hot environments with equivalent WBGT resulted in similar levels of thermal, cardiovascular, and perceptual strain, which support the use of the WBGT stress index. However, the greater IL-6 response in the Hot/Dry requires further research to elucidate the effects of different hot environments and work intensities.

How Academic Medicine Can Help Confront the Opioid Crisis.

The United States is in the midst of a devastating overdose and addiction crisis involving opioids as well as other drugs. Yet, despite the existence of effective treatments for opioid use disorder, only a minority of people who need treatment for this or other substance use disorders receive it. Besides the terrible human and economic costs of overdose deaths and the other health consequences of addiction, untreated substance use has wide-ranging impacts across health care. Academic medicine can help address this crisis by increasing the preparedness of the current and future clinical workforce to detect and treat substance misuse and addiction through increased attention to these topics in medical and nursing schools and in residency programs. In this commentary, the authors explore the barriers to treatment for substance misuse and addiction and the role of academic medicine in improving treatment outcomes through training, clinical care, health service delivery, and research.

HPA and SAS responses to increasing core temperature during uncompensable exertional heat stress in trained and untrained males.

Increases in core temperature (T (c)) augment stress hormones and neurotransmitters; however, the effect of different T (c) tolerated with varying fitness levels during uncompensable exertional heat stress (EHS) is unclear. The purpose was to examine the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic-adrenomedullary system (SAS) responses during uncompensable EHS in trained (TR) versus untrained (UT) males. Twelve TR and 11 UT (VO(2peak) = 70 +/-2 and 50 +/- 1 mL kg of lean body mass(-1) min(-1)) walked on a treadmill to exhaustion (EXH) in 40 degrees C (dry), dressed in protective clothing. PRE and 0.5 degrees C T (c) increments from 38.0-40.0 degrees C/EXH venous blood was obtained. Cortisol responded to absolute thermal strain, increasing throughout EHS and independent of fitness. Adrenocorticotropic Hormone, Norepinephrine, and Dehydroepiandrosterone-Sulphate responded to relative thermal strain with similar EXH values, despite higher T (c) tolerated for TR (39.7 degrees C) than UT (39.0 degrees C). Epinephrine, Growth Hormone (GH), and Aldosterone increased initially, with a plateau above 38.5 degrees C T (c). Findings demonstrate the complexity of the HPA axis, SAS, and T (c) relationship, with the stress pathways responding largely to relative thermal strain, although some hormones exhibited a clamping response likely as a protective mechanism. For the TR, evidence existed for a reduced pituitary sensitivity to glucocorticoids and the amplified GH may have contributed to their greater T (c) tolerated.

Hyperbaric stress in divers and non-divers: neuroendocrine and psychomotor responses.

This study compared neuroendocrine and psychomotor responses in divers (D, n = 11) and non-divers (ND, n = 9) following 30-minute hyperbaric and decompression stress to 180, 300 and 450 kPa. Venous blood was drawn pre-dive and at 20 and 60 minutes post-dive and analyzed for norepinephrine (NE), epinephrine (E), tryptophan (TRP), cortisol (COR), growth hormone (GH), adrenocorticotrophic hormone (ACTH) and prolactin (PRL). Reaction time was assessed using a psychomotor vigilance task. There was no difference between groups, across time or among levels of hyperbaric stress, for NE, E, TRP or GH. Small decreases over time in COR were noted. ACTH was significantly higher for ND at 20 minutes following 180 kPa and after 60 minutes for 450 kPa exposure. PRL increased significantly more for ND, and changes from baseline following 450 kPa exposure were moderately related (r = 0.52) to the significant slowing of reaction time at 20 minutes (296 +/- 55 msec) and 60 minutes (277 +/- 35 msec) compared with baseline (247 +/- 22 msec), although PRL returned to baseline levels faster than reaction time. It was concluded that for the stress hormones measured, PRL may provide some indication of the adaptation involved with repeated hyperbaric stress, but its relationship to changes in reaction time was weak.

Influence of hydration volume and ambient temperature on physiological responses while wearing CBRN protective clothing.

This study examined a low (L; 5 ml/kg per h) and high (H, 10 ml/kg per h) rate of fluid replacement in moderate (18°C) and hot (30°C) conditions on physiological responses while wearing personal protective equipment (PPE). PPE included the gas-tight suit (GTS), the powered respirator protective suit (PRPS) and the civil responder 1 (CR1). Relative to the moderate condition, physiological responses were greater in the hot condition. The percentage change in body mass was different (p < 0.05) between L and H in the hot (L vs. H, GTS: -0.83 vs. -0.38%; PRPS: -1.18 vs. -0.71%; CR1: -1.62 vs. -0.57%) and moderate conditions, although in GTS and CR1 body mass increased (L vs. H, GTS: -0.48 vs. 0.06%; PRPS: -0.66 vs. -0.11%; CR1: -0.18 vs. 0.67%). Fluid replacement strategies for PPE should be adjusted for environmental conditions in order to avoid >1% body mass loss and/or net body mass gain. STATEMENT OF RELEVANCE: Currently, the UK Emergency Services do not have specific evidence-based fluid replacement guidelines to follow when wearing chemical, biological, radiological and/or nuclear (CBRN) PPE. Although ad libitum fluid replacement is encouraged (when breathing apparatus permits), recommendations from evidence-based findings specific to different PPE and to different environmental conditions are lacking. This study provides novel evidence supporting the need to develop fluid replacement strategies during CBRN deployments in both moderate and hot environmental conditions for CBRN PPE.

Chemical-biological protective clothing: effects of design and initial state on physiological strain.

PURPOSE: This study examined whether heat strain during low states of chemical and biological protection (CB(low)) impacted tolerance time (TT) after transition to a high state of protection (CB(high)) and whether vents in the uniform reduced heat strain during CB(low) and increased TT. METHODS: There were eight men who walked at 35 degrees C in CB(low), and then transitioned to CB(high). Subjects wore fatigues in CB(low) with an overgarment during CB(high) (F+OG) or a new 1-piece (1PC) or 2PC uniform throughout CB(low) and CB(high). One condition also tested opened vents in the torso, arms, and legs of the 2PC uniform (2PC(vent)) during CB(low); these vents were closed during CB(high). Also worn were fragmentation and tactical vests and helmet. RESULTS: Heart rates were reduced significantly during CB(low) for F+OG and 2PC(vent) (114 +/- 13) vs. 1 PC and 2PC (122 +/- 18). Rectal temperature (T(re)) increased least in CB(low) for F+OG (0.86 +/- 0.23 degree C) and was significantly lower for 2PC(vent) (1.02 +/- 0.25 degree C) vs. 2PC (1.11 +/- 0.27 degree C). T(re) increased rapidly during CB(high) for F+OG, which had the shortest TT (40 +/- 9 min). Increased thermal strain during CB(low) for 1PC negated its advantage in CB(high) and TT (46 +/- 21 min) was similar to F+OG. Differences in T(re) between 2PC and 2PC(vent) remained during CB(high) whereTT was increased during 2PC(vent) (74 +/- 17 min) vs. 2PC (62 +/- 19 min). CONCLUSIONS: It was concluded that heat strain during CB(low) impacted TT during CB(high), and use of vents reduced heat strain during CB(low), thereby increasing TT.

Caffeine effects on physical and cognitive performance during sustained operations.

PURPOSE: This study examined caffeine (CAF) effects on physical performance and vigilance during 4 d and 3 nights of sustained operations in Special Forces personnel. METHODS: There were 20 soldiers (28.6 +/- 4.7 yr, 177.6 +/- 7.5 cm, 81.2 +/- 8.0 kg) who were divided equally into placebo (PLAC) and CAF groups. A 4-km run that included three obstacles (OBST) was completed each morning with the performance on Day 2 representing control (CON) after familiarization on Day 1 and an 8-h sleep. From 01:30 to 06:15 of Days 3-5, soldiers performed two 2-h vigilance (VIG) sessions in the field. PLAC or 200 mg of CAF was administered at 21:45 of Days 2-4 and at 01:00, 03:45, and approximately 07:00 on Days 3-5. The run commenced within 30 min of the final dose. Soldiers were provided a 4-h sleep period from 13:30-17:30 during Days 3 and 4. RESULTS: VIC during Days 3-5 was greater for CAF vs. PLAC and not different from CON. Total run time was faster for CAF (29.7 +/- 2.0 min) compared with PLAC (30.7 +/- 2.9 min) on Day 3 due to faster completion of OBST (8.7 +/- 0.7 min vs. 9.2 +/- 1.0 min for CAF and PLAC, respectively). Thereafter, run times decreased for both groups on Days 4 and 5 compared with CON due primarily to an increased pace between OBST. CONCLUSIONS: it was concluded that CAF maintained both vigilance and physical performance during sustained operations that require periods of overnight wakefulness and restricted opportunities for daytime sleep.

The management of heat stress for the firefighter: a review of work conducted on behalf of the Toronto Fire Service.

This report provides a summary of research conducted through a grant provided by the Workplace Safety Insurance Board of Ontario. The research was divided into two phases; first, to define safe work limits for firefighters wearing their protective clothing and working in warm environments; and, the second, to examine strategies to reduce the thermal burden and extend the operational effectiveness of the firefighter. For the first phase, subjects wore their protective ensemble and carried their self-contained breathing apparatus (SCBA) and performed very light, light, moderate or heavy work at 25 degrees C, 30 degrees C or 35 degrees C. Thermal and evaporative resistance coefficients were obtained from thermal manikin testing that allowed the human physiological responses to be compared with modeled data. Predicted continuous work times were then generated using a heat strain model that established limits for increases in body temperature to 38.0 degrees C, 38.5 degrees C and 39.0 degrees C. Three experiments were conducted for the second phase of the project. The first study revealed that replacing the duty uniform pants that are worn under the bunker pants with shorts reduced the thermal strain for activities that lasted longer than 60 min. The second study examined the importance of fluid replacement. The data revealed that fluid replacement equivalent to at least 65% of the sweat lost increased exposure time by 15% compared with no fluid replacement. The last experiment compared active and passive cooling. Both the use of a mister or forearm and hand submersion in cool water significantly increased exposure time compared with passive cooling that involved only removing most of the protective clothing. Forearm and hand submersion proved to be most effective and produced dramatic increases in exposure time that approximated 65% compared with the passive cooling procedure. When the condition of no fluid replacement and passive cooling was compared with fluid replacement and forearm and hand submersion, exposure times were effectively doubled with the latter condition. The heat stress wheel that was generated can be used by Commanders to determine safe work limits for their firefighters during activities that involve wearing their protective clothing and carrying their SCBA.