Most advice for improving physiological strain in the heat includes maintaining hydration using long-term acclimation protocols (>10 days). Therefore, the major aims of this thesis were to examine; (i) effectiveness of short term (5-day) heat acclimation (STHA) with moderately and highly trained athletes; (ii) fluid regulatory strain has a thermally-independent role in heat adaptation; and, (iii) impact of STHA on a marker of thermotolerancè (inducible heat shock protein 70; HSP70). Ten moderately trained males completed heat acclimation (Acc) under controlled hyperthermia (rectal temperature 38.5�C) for 90-min on five consecutive days (T[a] = 40�C, 60% RH), on two occasions separated by a five-week washout, in a cross-over design. One Acc was undertaken with euhydration (fluid replenishment; EUH) and one with dehydration (no fluid intake; DEH) during daily Acc bouts. Participants completed an exercising heat stress test (HST) one week before, then on the 2nd day after Acc for both regimes. HST involved cycling at 40% PPO for 90 min (T[a] = 35�C, 60% RH), 10 min rest and a ramp protocol (2% PPO each 30 s) to volitional fatigue. HSTs were further completed 1, 2, and 3 wks after Acc to track the acclimation decay. On a later occasion eight highly trained male rowers were heat acclimated under the same protocol but with DEH acclimation only and a rowing-specific HST (2000 m rowing performance test). Plasma volume (PV) at rest and cardiac output (Q̇) during HSTs were measured using CO and CO₂ rebreathing, respectively. A number of plasma constituents were measured: PV, AVP, aldosterone, HSP70, total protein, albumin, Na⁺, K⁺, Cl⁻ and osmolality. Short term heat acclimation resulted in physiological adaptation and enhanced exercise capacity for moderately trained participants. Compared to EUH permissive DEH during Acc bouts conferred larger acclimation-induced increases in resting PV by 4.1% (95%CI: -1.5 to 9.8%; p=0.06), Q̇[F]. (4.2: 0.7 to 7.8 mlmin⁻� 100 ml⁻�; p0.009), FVC (0.06: 0.02 to 0.10 ml 100ml Tissue⁻�mmHg⁻�; p=0.006), end-exercise V[s] (45.9: 3.6 to 84.4 mL; p=0.02) and decreased end-exercise f[c] by 17% (19: -29 to 9 b�min⁻�; p=0.08). Cardiovascular adaptations except PV persisted for one wk, but not two wks after Acc indicating that cardiovascular-related benefits from STHA may not be mediated by hypervolaemic responses per se. The highly trained athletes had functional heat adaptations of similar magnitude to lesser fitness-adapted participants across DEH acclimation, including resting PV expansion (4.5: 0.7 to 8.3%) and increased performance (-4.0: -6.3 to 0.6[s]; p=0.02). Plasma total protein-corrected HSP70 concentration increased from rest to end-exercise across acclimation (p=0.001). There was a greater change from rest to end-exercise on day one versus day five Acc (p=0.05), indicating a reduced stress-induced increase and a protective adaptive change. There were weak to moderate relationships between hydration indices in dynamic circumstances indicating that there is no single measure to accurately assess hydration status. In conclusion, short-term (5-day) heat acclimation was effective with adaptations more pronounced after fluid regulatory strain from a dehydration acclimation regime. Similar findings were found using highly trained and lesser- fitness adapted participants. Thermotolerance was increased by dehydration acclimation.

Most advice for improving physiological strain in the heat includes maintaining hydration using long-term acclimation protocols (>10 days). Therefore, the major aims of this thesis were to examine; (i) effectiveness of short term (5-day) heat acclimation (STHA) with moderately and highly trained athletes; (ii) fluid regulatory strain has a thermally-independent role in heat adaptation; and, (iii) impact of STHA on a marker of thermotolerancè (inducible heat shock protein 70; HSP70). Ten moderately trained males completed heat acclimation (Acc) under controlled hyperthermia (rectal temperature 38.5�C) for 90-min on five consecutive days (T[a] = 40�C, 60% RH), on two occasions separated by a five-week washout, in a cross-over design. One Acc was undertaken with euhydration (fluid replenishment; EUH) and one with dehydration (no fluid intake; DEH) during daily Acc bouts. Participants completed an exercising heat stress test (HST) one week before, then on the 2nd day after Acc for both regimes. HST involved cycling at 40% PPO for 90 min (T[a] = 35�C, 60% RH), 10 min rest and a ramp protocol (2% PPO each 30 s) to volitional fatigue. HSTs were further completed 1, 2, and 3 wks after Acc to track the acclimation decay. On a later occasion eight highly trained male rowers were heat acclimated under the same protocol but with DEH acclimation only and a rowing-specific HST (2000 m rowing performance test). Plasma volume (PV) at rest and cardiac output (Q̇) during HSTs were measured using CO and CO₂ rebreathing, respectively. A number of plasma constituents were measured: PV, AVP, aldosterone, HSP70, total protein, albumin, Na⁺, K⁺, Cl⁻ and osmolality. Short term heat acclimation resulted in physiological adaptation and enhanced exercise capacity for moderately trained participants. Compared to EUH permissive DEH during Acc bouts conferred larger acclimation-induced increases in resting PV by 4.1% (95%CI: -1.5 to 9.8%; p=0.06), Q̇[F]. (4.2: 0.7 to 7.8 mlmin⁻� 100 ml⁻�; p0.009), FVC (0.06: 0.02 to 0.10 ml 100ml Tissue⁻�mmHg⁻�; p=0.006), end-exercise V[s] (45.9: 3.6 to 84.4 mL; p=0.02) and decreased end-exercise f[c] by 17% (19: -29 to 9 b�min⁻�; p=0.08). Cardiovascular adaptations except PV persisted for one wk, but not two wks after Acc indicating that cardiovascular-related benefits from STHA may not be mediated by hypervolaemic responses per se. The highly trained athletes had functional heat adaptations of similar magnitude to lesser fitness-adapted participants across DEH acclimation, including resting PV expansion (4.5: 0.7 to 8.3%) and increased performance (-4.0: -6.3 to 0.6[s]; p=0.02). Plasma total protein-corrected HSP70 concentration increased from rest to end-exercise across acclimation (p=0.001). There was a greater change from rest to end-exercise on day one versus day five Acc (p=0.05), indicating a reduced stress-induced increase and a protective adaptive change. There were weak to moderate relationships between hydration indices in dynamic circumstances indicating that there is no single measure to accurately assess hydration status. In conclusion, short-term (5-day) heat acclimation was effective with adaptations more pronounced after fluid regulatory strain from a dehydration acclimation regime. Similar findings were found using highly trained and lesser- fitness adapted participants. Thermotolerance was increased by dehydration acclimation.

High temperatures are a significant biological stressor for mammals, which they may adapt to through behavioral changes, physiological plasticity, and via genetic adaptation. Savanna monkeys (genus Chlorocebus) have a wide climatic range in Africa south of the Sahara, making them a good model species for understanding adaptations to heat stress in primates. Savanna monkeys have been observed to behaviorally mitigate high temperatures, and genetic signs of selection in response to climate have also been found (specifically in relation to cold). In this study, I investigate whether there is genetic variation and evidence for selection related to function in a heat shock protein gene (HSPA1L) in 73 wild savanna monkeys ranging from equatorial Africa to the southern coast of South Africa. Given the important role of heat shock proteins in buffering heat stress, I hypothesized that genetic variation would be associated with maximum summer temperatures, as those are most likely to be warm enough to induce a heat shock response. I found 45 single nucleotide polymorphisms (SNPs) outside of Hardy-Weinberg Equilibrium, and 10 SNPs with significant integrated haplotype scores, only one of which was in a protein coding region (17:40210341; piHS = 2.20). Using phylogenetic least squares modeling I found that maximum temperature of the warmest month was strongly but not significantly associated with the frequency of a derived allele nested within a regulatory region for HSPA1L (17:40207386; piHS = 2.57; b = 0.044, p = 0.061) presumably experiencing selection. I discuss implications of these results for heat tolerance in primates and resilience to climate change.

Childhood asthma is one of the most common chronic diseases worldwide, including in South Africa. There has been substantial evidence on the role of air pollution in asthma exacerbation but limited research on the role of climate change and how the interaction between climate change and air pollution is affecting childhood asthma, specifically in low and middle-income countries (LMICs). Temperature changes can be used as an effect of climate change to investigate the association between climate change, air pollution and childhood asthma. This study, therefore, used a case study approach aimed at examining the interaction between air pollution and temperature in exacerbating childhood asthma focusing on clinical data obtained from Red Cross War Memorial Children's Hospital, air quality data (City of Cape Town) and temperature data (South African Weather Services) for Cape Town, South Africa for three study years (2009, 2014 and 2019). The protocol (Part A) of the mini dissertation describes childhood asthma literature globally and in LMICs and specifically in South Africa. It also discusses the increasing incidences and prevalence of the disease and possible causes such as air pollution and climate change. Furthermore, it discusses the vulnerability of children to the exposure of interest, being air pollution (PM2.5, PM10, NO2 and O3) and climate change (i.e., temperature). Subsequently, the development of air quality standards is discussed, specifically concerning whether they consider the specific children's vulnerability to exposures. The protocol then describes the study population and methodologies for conducting this study. The journal ready article (Part B) presents the findings of the study. Spearman's correlation was used to measure the degree of association between temperature variables and air pollutants. The results indicated that diurnal temperature was associated with PM2.5 (r=0.579: p< 0.01) and PM10 (r=0.505: p< 0.01). A Poisson regression analysis was applied to evaluate the relationship between asthma exacerbation with air pollutants and temperature variables. In a univariate analysis there was a statistically significant relationship between asthma exacerbation and diurnal temperature for 2019, IRR=0.98 (95% CI,0.97 – 0.99) p< 0.05, maximum temperature 2014, IRR=0.99(95% CI, 0.98 - 1.00) p< 0.05 and for 2019, IRR=0.98(95% CI, 0.97 - 0.99) p< 0.01, average temperature 2014, IRR=0.99(95% CI, 0.98 - 1.00) p< 0.05 and for 2019, IRR=0.98(95% CI, 0.97 - 0.99) p< 0.01. Using a multivariate analysis there v of 110 was no significant relationship between childhood asthma exacerbation and air pollutants (PM10, NO2 and O3) except for PM2.5 IRR=0.12(95% CI, 0.01 - 0.81) p< 0.05. Diurnal temperature statistically significant childhood asthma predictor for 2009, IRR=1.02(95% CI, 1.00 - 1.05) p< 0.05 and for 2014, IRR=0.97(95% CI, 0.96 - 0.99) p< 0.01. Temperature increase, therefore, seems to be related to asthma exacerbation. More research is needed on the relationship between diurnal temperature, childhood asthma, and air pollutants to inform adaptation strategies. The findings of this study are important for the development of climate change and health adaptation and prevention strategies in South Africa, particularly in relation to heat adaptation. These findings are also relevant for the development of air quality guidelines and guidelines to address children, as the most vulnerable population to environmental health exposures. The appendices (Part C) present the analyses that were not included in the protocol (Part A) and article (Part B). These also include documents relating to the study such as ethics approval and permission to conduct research by different entities.