Measuring human capital using global learning data.

Human capital-that is, resources associated with the knowledge and skills of individuals-is a critical component of economic development1,2. Learning metrics that are comparable for countries globally are necessary to understand and track the formation of human capital. The increasing use of international achievement tests is an important step in this direction3. However, such tests are administered primarily in developed countries4, limiting our ability to analyse learning patterns in developing countries that may have the most to gain from the formation of human capital. Here we bridge this gap by constructing a globally comparable database of 164 countries from 2000 to 2017. The data represent 98% of the global population and developing economies comprise two-thirds of the included countries. Using this dataset, we show that global progress in learning-a priority Sustainable Development Goal-has been limited, despite increasing enrolment in primary and secondary education. Using an accounting exercise that includes a direct measure of schooling quality, we estimate that the role of human capital in explaining income differences across countries ranges from a fifth to half; this result has an intermediate position in the wide range of estimates provided in earlier papers in the literature5-13. Moreover, we show that average estimates mask considerable heterogeneity associated with income grouping across countries and regions. This heterogeneity highlights the importance of including countries at various stages of economic development when analysing the role of human capital in economic development. Finally, we show that our database provides a measure of human capital that is more closely associated with economic growth than current measures that are included in the Penn world tables version 9.014 and the human development index of the United Nations15.

An intercellular heme-trafficking protein delivers maternal heme to the embryo during development in C. elegans.

Extracellular free heme can intercalate into membranes and promote damage to cellular macromolecules. Thus it is likely that specific intercellular pathways exist for the directed transport, trafficking, and delivery of heme to cellular destinations, although none have been found to date. Here we show that Caenorhabditis elegans HRG-3 is required for the delivery of maternal heme to developing embryos. HRG-3 binds heme and is exclusively secreted by maternal intestinal cells into the interstitial fluid for transport of heme to extraintestinal cells, including oocytes. HRG-3 deficiency results either in death during embryogenesis or in developmental arrest immediately post-hatching-phenotypes that are fully suppressed by maternal but not zygotic hrg-3 expression. Our results establish a role for HRG-3 as an intercellular heme-trafficking protein.

Uncoupling of Ca2+ sparks from BK channels in cerebral arteries underlies hypoperfusion in hypertension-induced vascular dementia.

The deficit in cerebral blood flow (CBF) seen in patients with hypertension-induced vascular dementia is increasingly viewed as a therapeutic target for disease-modifying therapy. Progress is limited, however, due to uncertainty surrounding the mechanisms through which elevated blood pressure reduces CBF. To investigate this, we used the BPH/2 mouse, a polygenic model of hypertension. At 8 mo of age, hypertensive mice exhibited reduced CBF and cognitive impairment, mimicking the human presentation of vascular dementia. Small cerebral resistance arteries that run across the surface of the brain (pial arteries) showed enhanced pressure-induced constriction due to diminished activity of large-conductance Ca2+-activated K+ (BK) channels-key vasodilatory ion channels of cerebral vascular smooth muscle cells. Activation of BK channels by transient intracellular Ca2+ signals from the sarcoplasmic reticulum (SR), termed Ca2+ sparks, leads to hyperpolarization and vasodilation. Combining patch-clamp electrophysiology, high-speed confocal imaging, and proximity ligation assays, we demonstrated that this vasodilatory mechanism is uncoupled in hypertensive mice, an effect attributable to physical separation of the plasma membrane from the SR rather than altered properties of BK channels or Ca2+ sparks, which remained intact. This pathogenic mechanism is responsible for the observed increase in constriction and can now be targeted as a possible avenue for restoring healthy CBF in vascular dementia.

Functionally linked potassium channel activity in cerebral endothelial and smooth muscle cells is compromised in Alzheimer's disease.

The brain microcirculation is increasingly viewed as a potential target for disease-modifying drugs in the treatment of Alzheimer's disease patients, reflecting a growing appreciation of evidence that cerebral blood flow is compromised in such patients. However, the pathogenic mechanisms in brain resistance arteries underlying blood flow defects have not yet been elucidated. Here we probed the roles of principal vasodilatory pathways in cerebral arteries using the APP23 mouse model of Alzheimer's disease, in which amyloid precursor protein is increased approximately sevenfold, leading to neuritic plaques and cerebrovascular accumulation of amyloid-ß similar to those in patients with Alzheimer's disease. Pial arteries from APP23 mice (18 mo old) exhibited enhanced pressure-induced (myogenic) constriction because of a profound reduction in ryanodine receptor-mediated, local calcium-release events ("Ca2+ sparks") in arterial smooth muscle cells and a consequent decrease in the activity of large-conductance Ca2+-activated K+ (BK) channels. The ability of the endothelial cell inward rectifier K+ (Kir2.1) channel to cause dilation was also compromised. Acute application of amyloid-ß 1-40 peptide to cerebral arteries from wild-type mice partially recapitulated the BK dysfunction seen in APP23 mice but had no effect on Kir2.1 function. If mirrored in human Alzheimer's disease, these tandem defects in K+ channel-mediated vasodilation could account for the clinical cerebrovascular presentation seen in patients: reduced blood flow and crippled functional hyperemia. These data direct future research toward approaches that reverse this dual vascular channel dysfunction, with the ultimate aim of restoring healthy cerebral blood flow and improving clinical outcomes.

Third Harmonic Generation Enhancement and Wavefront Control Using a Local High-Q Metasurface.

High quality factor optical nanostructures provide a great opportunity to enhance nonlinear optical processes such as third harmonic generation. However, the field enhancement in these high quality factor structures is typically accompanied by optical mode nonlocality. As a result, the enhancement of nonlinear processes comes at the cost of their local control as needed for nonlinear wavefront shaping, imaging, and holography. Here we show simultaneous strong enhancement and spatial control over third harmonic generation with a local high-Q metasurface relying on higher-order Mie resonant modes. Our results demonstrate third harmonic generation at an efficiency of up to 3.25 × 10-5, high quality wavefront shaping as illustrated by a third harmonic metalens, and a flatband, angle independent, third harmonic response up to ±11° incident angle. The demonstrated high level of local control and efficient frequency conversion offer promising prospects for realizing novel nonlinear optical devices.

Molecular Additives Improve the Selectivity of CO2 Photoelectrochemical Reduction over Gold Nanoparticles on Gallium Nitride.

Photoelectrochemical CO2 reduction (CO2R) is an appealing solution for converting carbon dioxide into higher-value products. However, CO2R in aqueous electrolytes suffers from poor selectivity due to the competitive hydrogen evolution reaction that is dominant on semiconductor surfaces in aqueous electrolytes. We demonstrate that functionalizing gold/p-type gallium nitride devices with a film derived from diphenyliodonium triflate suppresses hydrogen generation from 90% to 18%. As a result, we observe increases in the Faradaic efficiency and partial current density for carbon monoxide of 50% and 3-fold, respectively. Furthermore, we demonstrate through optical absorption measurements that the molecular film employed herein, regardless of thickness, does not affect the photocathode's light absorption. Altogether, this study provides a rigorous platform for elucidating the catalytic structure-property relationships to enable engineering of active, stable, and selective materials for photoelectrochemical CO2R.

Electrochemical CO2 Reduction in Acidic Electrolytes: Spectroscopic Evidence for Local pH Gradients.

Inspired by recent advances in electrochemical CO2 reduction (CO2R) under acidic conditions, herein we leverage in situ spectroscopy to inform the optimization of CO2R at low pH. Using attenuated total reflection surface-enhanced infrared absorption spectroscopy (ATR-SEIRAS) and fluorescent confocal laser scanning microscopy, we investigate the role that alkali cations (M+) play on electrochemical CO2R. This study hence provides important information related to the local electrode surface pH under bulk acidic conditions for CO2R, both in the presence and absence of an organic film layer, at variable [M+]. We show that in an acidic electrolyte, an appropriate current density can enable CO2R in the absence of metal cations. In situ local pH measurements suggest the local [H+] must be sufficiently depleted to promote H2O reduction as the competing reaction with CO2R. Incrementally incorporating [K+] leads to increases in the local pH that promotes CO2R but only at proton consumption rates sufficient to drive the pH up dramatically. Stark tuning measurements and analysis of surface water structure reveal no change in the electric field with [M+] and a desorption of interfacial water, indicating that improved CO2R performance is driven by suppression of H+ mass transport and modification of the interfacial solvation structure. In situ pH measurements confirm increasing local pH, and therefore decreased local [CO2], with [M+], motivating alternate means of modulating proton transport. We show that an organic film formed via in situ electrodeposition of an organic additive provides a means to achieve selective CO2R (FECO2R ∼ 65%) over hydrogen evolution reaction in the presence of strong acid (pH 1) and low cation concentrations (≤0.1 M) at both low and high current densities.

Placebo Effects Are Small on Average in the 7.5% CO2 Inhalational Model of Generalized Anxiety.

BACKGROUND: Anxiety disorders are highly prevalent and socio-economically costly. Novel pharmacological treatments for these disorders are needed because many patients do not respond to current agents or experience unwanted side effects. However, a barrier to treatment development is the variable and large placebo response rate seen in trials of novel anxiolytics. Despite this, the mechanisms that drive placebo responses in anxiety disorders have been little investigated, possibly due to low availability of convenient experimental paradigms. We aimed to develop and test a novel protocol for inducing placebo anxiolysis in the 7.5% CO2 inhalational model of generalized anxiety in healthy volunteers. METHODS: Following a baseline 20-minute CO2 challenge, 32 healthy volunteers were administered a placebo intranasal spray labelled as either the anxiolytic "lorazepam" or "saline." Following this, participants surreptitiously underwent a 20-minute inhalation of normal air. Post-conditioning, a second dose of the placebo was administered, after which participants completed another CO2 challenge. RESULTS: Participants administered sham "lorazepam" reported significant positive expectations of reduced anxiety (P = .001), but there was no group-level placebo effect on anxiety following CO2 challenge post-conditioning (Ps > .350). Surprisingly, we found many participants exhibited unexpected worsening of anxiety, despite positive expectations. CONCLUSIONS: Contrary to our hypothesis, our novel paradigm did not induce a placebo response, on average. It is possible that effects of 7.5% CO2 inhalation on prefrontal cortex function or behavior in line with a Bayesian predictive coding framework attenuated the effect of expectations on subsequent placebo response. Future studies are needed to explore these possibilities.

Acute, pro-contractile effects of prorenin on rat mesenteric arteries.

Prorenin and the prorenin receptor ((P)RR) are important, yet controversial, members of the renin-angiotensin-aldosterone system. The ((P)RR) is expressed throughout the body, including the vasculature, however, the direct effect of prorenin on arterial contractility is yet to be determined. Within rat mesenteric arteries, immunostaining and proximity ligation assays were used to determine the interacting partners of (P)RR in freshly isolated vascular smooth muscle cells (VSMCs). Wire myography examined the functional effect of prorenin. Simultaneous changes in [Ca2+ ]i and force were recorded in arteries loaded with Fura-2AM. Spontaneously transient outward currents were recorded via perforated whole-cell patch-clamp configuration in freshly isolated VSMCs. We found that the (P)RR is located within a distance of less than 40 nm from the V-ATPase, caveolin-1, ryanodine receptors, and large conductance Ca2+ -activated K+ channels (BKCa ) in VSMCs. [Ca2+ ]i imaging and isometric tension recordings indicate that 1 nM prorenin enhanced α1-adrenoreceptor-mediated contraction, associated with an increased number of Ca2+ waves, independent of voltage-gated Ca2+ channels activation. Incubation of VSMCs with 1 nM prorenin decreased the amplitude and frequency of spontaneously transient outward currents and attenuated BKCa -mediated relaxation. Inhibition of the V-ATPase with 100 nM bafilomycin prevented prorenin-mediated inhibition of BKCa -derived relaxation. Renin (1 nM) had no effect on BKCa -mediated relaxation. In conclusion, prorenin enhances arterial contractility by inhibition of BKCa and increasing intracellular Ca2+ release. It is likely that this effect is mediated through a local shift in pH upon activation of the (P)RR and stimulation of the V-ATPase.

Myths and Methodologies: Standardisation in human physiology research-should we control the controllables?

The premise of research in human physiology is to explore a multifaceted system whilst identifying one or a few outcomes of interest. Therefore, the control of potentially confounding variables requires careful thought regarding the extent of control and complexity of standardisation. One common factor to control prior to testing is diet, as food and fluid provision may deviate from participants' habitual diets, yet a self-report and replication method can be flawed by under-reporting. Researchers may also need to consider standardisation of physical activity, whether it be through familiarisation trials, wash-out periods, or guidance on levels of physical activity to be achieved before trials. In terms of pharmacological agents, the ethical implications of standardisation require researchers to carefully consider how medications, caffeine consumption and oral contraceptive prescriptions may affect the study. For research in females, it should be considered whether standardisation between- or within-participants in regards to menstrual cycle phase is most relevant. The timing of measurements relative to various other daily events is relevant to all physiological research and so it can be important to standardise when measurements are made. This review summarises the areas of standardisation which we hope will be considered useful to anyone involved in human physiology research, including when and how one can apply standardisation to various contexts.

Effects of physical form of ß-lactoglobulin and calcium ingestion on GLP-1 secretion, gastric emptying and energy intake in humans: a randomised crossover trial.

The aim of this study was to assess whether adding Ca2+ to aggregate or native forms of ß-lactoglobulin alters gut hormone secretion, gastric emptying rates and energy intake in healthy men and women. Fifteen healthy adults (mean ± sd: 9M/6F, age: 24 ± 5 years) completed four trials in a randomised, double-blind, crossover design. Participants consumed test drinks consisting of 30 g of ß-lactoglobulin in a native form with (NATIVE + MINERALS) and without (NATIVE) a Ca2+-rich mineral supplement and in an aggregated form both with (AGGREG + MINERALS) and without the mineral supplement (AGGREG). Arterialised blood was sampled for 120 min postprandially to determine gut hormone concentrations. Gastric emptying was determined using 13C-acetate and 13C-octanoate, and energy intake was assessed with an ad libitum meal at 120 min. A protein × mineral interaction effect was observed for total glucagon-like peptide-1 (GLP-1TOTAL) incremental AUC (iAUC; P < 0·01), whereby MINERALS + AGGREG increased GLP-1TOTAL iAUC to a greater extent than AGGREG (1882 ± 603 v. 1550 ± 456 pmol·l-1·120 min, P < 0·01), but MINERALS + NATIVE did not meaningfully alter the GLP-1 iAUC compared with NATIVE (1669 ± 547 v. 1844 ± 550 pmol·l-1·120 min, P = 0·09). A protein × minerals interaction effect was also observed for gastric emptying half-life (P < 0·01) whereby MINERALS + NATIVE increased gastric emptying half-life compared with NATIVE (83 ± 14 v. 71 ± 8 min, P < 0·01), whereas no meaningful differences were observed between MINERALS + AGGREG v. AGGREG (P = 0·70). These did not result in any meaningful changes in energy intake (protein × minerals interaction, P = 0·06). These data suggest that the potential for Ca2+ to stimulate GLP-1 secretion at moderate protein doses may depend on protein form. This study was registered at clinicaltrials.gov (NCT04659902).

Society for Research on Nicotine and Tobacco as an Outgrowth of the 1988 Surgeon General's Report on Nicotine Addiction: Reflections of the Early Presidents.

INTRODUCTION: The Society for Research on Nicotine and Tobacco began in the United States as a scientific organization "to stimulate the generation and dissemination of new knowledge concerning nicotine and tobacco in all its manifestations." Now in its 30th year, the Society is taking on new challenges in tobacco control, nicotine vaping, product regulation, and public policy. AIMS AND METHODS: This Review describes the formative years of the Society from the perspective of researchers who were in leadership positions during that time, documenting how biobehavioral and clinical research in the first 10 years was a continuation of the scientific mission of the 1988 United States Surgeon General's Report on Nicotine Addiction and summarizing organizational innovations during each president's term of office. CONCLUSIONS: The Society's promotion of scientific research served as a catalyst for funding, policy, and regulation, setting the stage for its influence and credibility. IMPLICATIONS: This Commentary provides context and an overview of the scientific research and the organizational innovations that occurred during the early years of the Society for Research on Nicotine and Tobacco using publications and available documentation. The Society was able to thrive because biobehavioral research on nicotine addiction provided the scientific underpinnings for the tobacco control enterprise as a whole. The objective of this Commentary is to describe formative events in the Society's history based on the accomplishments of its early leaders.

Subwavelength integrated photonics.

In the late nineteenth century, Heinrich Hertz demonstrated that the electromagnetic properties of materials are intimately related to their structure at the subwavelength scale by using wire grids with centimetre spacing to manipulate metre-long radio waves. More recently, the availability of nanometre-scale fabrication techniques has inspired scientists to investigate subwavelength-structured metamaterials with engineered optical properties at much shorter wavelengths, in the infrared and visible regions of the spectrum. Here we review how optical metamaterials are expected to enhance the performance of the next generation of integrated photonic devices, and explore some of the challenges encountered in the transition from concept demonstration to viable technology.

Effect of sportswear on performance and physiological heat strain during prolonged running in moderately hot conditions.

INTRODUCTION: This study examined the impact of different upper-torso sportswear technologies on the performance and physiological heat strain of well-trained and national-level athletes during prolonged running in moderately hot conditions. METHODS: A randomized crossover design was employed in which 20 well-trained (n = 16) and national-level (n = 4) athletes completed four experimental trials in moderately hot conditions (35°C, 30% relative humidity). In each trial, participants ran at 70% of their peak oxygen uptake (70% V̇O2peak ) for 60 min, while wearing a different upper-body garment: cotton t-shirt, t-shirt with sweat-wicking fabric, compression t-shirt, and t-shirt with aluminum dots lining the inside of the upper back of the garment. Running speed was adjusted to elicit the predetermined oxygen consumption associated with 70% V̇O2peak . Physiological (core and skin temperatures, total body water loss, and urine specific gravity) and perceptual (thermal comfort and sensation, ratings of perceived exertion, and garment cooling functionality) parameters along with running speed at 70% V̇O2peak were continuously recorded. RESULTS: No significant differences were observed between the four garments for running speed at 70% V̇O2peak , physiological heat strain, and perceptual responses (all p > 0.05). The tested athletes reported larger areas of perceived suboptimal cooling functionality in the cotton t-shirt and the t-shirt with aluminum dots relative to the sweat-wicking and compression t-shirts (d: 0.43-0.52). CONCLUSION: There were not differences among the tested garments regarding running speed at 70% V̇O2peak , physiological heat strain, and perceptual responses in well-trained and national-level endurance athletes exercising in moderate heat.

Reliability and validity of the MX3 portable sweat sodium analyser during exercise in warm conditions.

PURPOSE: Accurately measuring sweat sodium concentration ([Na+]) in the field is advantageous for coaches, scientists, and dieticians looking to tailor hydration strategies. The MX3 hydration testing system is a new portable analyser that uses pre-calibrated biosensors to measure sweat [Na+]. This study aimed to assess the validity and reliability of the MX3 hydration testing system. METHODS: Thirty-one (11 females) recreationally active participants completed one experimental trial. During this trial, participants exercised at a self-selected pace for 45 min in a warm environment (31.5 ± 0.8 °C, 63.2 ± 1.3% relative humidity). Sweat samples were collected from three measurement sites using absorbent patches. The samples were then analysed for sweat [Na+] using both the MX3 hydration testing system and the Horiba LAQUAtwin-NA-11. The reliability of the MX3 hydration testing system was determined following two measurements of the same sweat sample. RESULTS: The mean difference between measurements was 0.1 mmoL·L-1 (95% limits of agreement (LoA): - 9.2, 9.4). The analyser demonstrated a coefficient of variation (CV) of 5.6% and the standard error of measurement was 3.3 mmoL·L-1. When compared to the Horiba LAQUAtwin-NA-11, there was a mean difference of - 1.7 mmoL·L-1 (95% LoA: - 0.25 X ¯ , 0.25 X ¯ ) and the CV was 9.8%. CONCLUSION: The MX3 hydration testing system demonstrated very good single-trial reliability, moderate agreement and a very good CV relative to the Horiba LAQUAtwin-Na-11. To further validate its performance, the MX3 hydration testing system should be compared with analytical techniques known for superior reliability and validity.

Quantifying bacterial evolution in the wild: A birthday problem for Campylobacter lineages.

Measuring molecular evolution in bacteria typically requires estimation of the rate at which nucleotide changes accumulate in strains sampled at different times that share a common ancestor. This approach has been useful for dating ecological and evolutionary events that coincide with the emergence of important lineages, such as outbreak strains and obligate human pathogens. However, in multi-host (niche) transmission scenarios, where the pathogen is essentially an opportunistic environmental organism, sampling is often sporadic and rarely reflects the overall population, particularly when concentrated on clinical isolates. This means that approaches that assume recent common ancestry are not applicable. Here we present a new approach to estimate the molecular clock rate in Campylobacter that draws on the popular probability conundrum known as the 'birthday problem'. Using large genomic datasets and comparative genomic approaches, we use isolate pairs that share recent common ancestry to estimate the rate of nucleotide change for the population. Identifying synonymous and non-synonymous nucleotide changes, both within and outside of recombined regions of the genome, we quantify clock-like diversification to estimate synonymous rates of nucleotide change for the common pathogenic bacteria Campylobacter coli (2.4 x 10-6 s/s/y) and Campylobacter jejuni (3.4 x 10-6 s/s/y). Finally, using estimated total rates of nucleotide change, we infer the number of effective lineages within the sample time frame-analogous to a shared birthday-and assess the rate of turnover of lineages in our sample set over short evolutionary timescales. This provides a generalizable approach to calibrating rates in populations of environmental bacteria and shows that multiple lineages are maintained, implying that large-scale clonal sweeps may take hundreds of years or more in these species.

Efficacy of the FIFA cooling break heat policy during an intermittent treadmill football simulation in hot conditions in trained males.

OBJECTIVE: To evaluate the efficacy of the Fédération Internationale de Football Association (FIFA) cooling break policy against alternative cooling configurations in attenuating thermal strain during simulated football in the heat. METHODS: 12 males (age: 27±6 years, V̇O2peak: 61±7 mL/kg/min) completed five 90 min intermittent treadmill football match simulations in 40°C and 41% relative humidity (32°C wet-bulb globe temperature) with different cooling configurations: regular match without cooling breaks (REG), 3 min breaks without cooling (BRKno-cool), 3 min breaks with cooling (BRKcool: current FIFA policy; chilled fluid ingestion and ice towel across neck and shoulders), 5 min extended half-time without cooling breaks (ExtHTonly) and 3 min cooling breaks with 5 min ExtHT (ExtHTcool). Rectal temperature (Tre), heart rate, whole-body sweat rate (WBSR) and rating of perceived exertion (RPE) were recorded. Data are presented as mean (95% CIs). RESULTS: Final Tre was lower in BRKno-cool (0.20°C (0.01, 0.39), p=0.038), BRKcool (0.39°C (0.21, 0.57), p<0.001) and ExtHTcool (0.40°C (0.22, 0.58), p<0.001) than REG (39.1°C (38.8, 39.3)). Mean Tre was lower in ExtHTcool (38.2°C (38.0, 38.4)) than BRKcool (38.3°C (38.1, 38.5), p=0.018), BRKno-cool and ExtHTonly (38.4°C (38.2, 38.6), p<0.001) and REG (38.5°C (38.3, 38.7), p<0.001). Mean heart rate was lower during BRKcool (6 beats/min (4, 7), p<0.001) and ExtHTcool (7 beats/min (6, 8), p<0.001) compared with REG. WBSR was comparable across trials (p≥0.07) and RPE was attenuated during BRKcool (0.4 (0.1, 0.7), p=0.004) and ExtHTcool (0.5 (0.2, 0.7), p=0.002), compared with REG. CONCLUSION: BRKcool and ExtHTcool attenuated thermal, cardiovascular and perceptual strain during a simulated football match in the heat. Additional strategies may be required in field settings or under harsher conditions.

Postoperative Elbow Instability: Options for Revision Stabilization.

Persistent and recurrent postoperative elbow instability includes a spectrum of pathologies ranging from joint incongruity and subluxation to dislocation. Restoration of osseous anatomy, particularly the coronoid, is a priority in restoring elbow alignment and maintaining ulnohumeral joint stability. After managing bony deficiencies, soft-tissue and ligamentous structures are typically addressed. When required, both static and dynamic adjunctive stabilization procedures have been described, which aid in maintaining a concentric reduction. In these complex procedures, both complication avoidance and early recognition of postoperative complications assist in obtaining a good result. In this review, we discuss current treatment options for revision stabilization for patients with persistent and recurrent elbow subluxation or dislocation after primary stabilization.

Myths and Methodologies: Standardisation in Human Physiology Research-Should We Control the Controllables?

The premise of research in human physiology is to explore a multifaceted system whilst identifying one or a few outcomes of interest. Therefore, the control of potentially confounding variables requires careful thought regarding the extent of control and complexity of standardisation. One common factor to control prior to testing is diet, as food and fluid provision may deviate from participants' habitual diets, yet a self-report and replication method can be flawed by under-reporting. Researchers may also need to consider standardisation of physical activity, whether it be through familiarisation trials, wash-out periods, or guidance on levels of physical activity to be achieved before trials. In terms of pharmacological agents, the ethical implications of standardisation require researchers to carefully consider how medications, caffeine consumption and oral contraceptive prescriptions may affect the study. For research in females, it should be considered whether standardisation between- or within-participants in regards to menstrual cycle phase is most relevant. The timing of measurements relative to various other daily events is relevant to all physiological research and so it can be important to standardise when measurements are made. This review summarises the areas of standardisation which we hope will be considered useful to anyone involved in human physiology research, including when and how one can apply standardisation to various contexts.

Auditing the Representation of Females Versus Males in Heat Adaptation Research.

The aim of this audit was to quantify female representation in research on heat adaptation. Using a standardized audit tool, the PubMed database was searched for heat adaptation literature from inception to February 2023. Studies were included if they investigated heat adaptation among female and male adults (≥18-50 years) who were free from noncommunicable diseases, with heat adaptation the primary or secondary outcome of interest. The number and sex of participants, athletic caliber, menstrual status, research theme, journal impact factor, Altmetric score, Field-Weighted Citation Impact, and type of heat exposure were extracted. A total of 477 studies were identified in this audit, including 7,707 participants with ∼13% of these being female. Most studies investigated male-only cohorts (∼74%, n = 5,672 males), with ∼5% (n = 360 females) including female-only cohorts. Of the 126 studies that included females, only 10% provided some evidence of appropriate methodological control to account for ovarian hormone status, with no study meeting best-practice recommendations. Of the included female participants, 40% were able to be classified to an athletic caliber, with 67% of these being allocated to Tier 2 (i.e., trained/developmental) or below. Exercise heat acclimation was the dominant method of heat exposure (437 interventions), with 21 studies investigating sex differences in exercise heat acclimation interventions. We recommend that future research on heat adaptation in female participants use methodological approaches that consider the potential impact of sexual dimorphism on study outcomes to provide evidence-based guidelines for female athletes preparing for exercise or competition in hot conditions.