STAR_outliers: a python package that separates univariate outliers from non-normal distributions.

There are not currently any univariate outlier detection algorithms that transform and model arbitrarily shaped distributions to remove univariate outliers. Some algorithms model skew, even fewer model kurtosis, and none of them model bimodality and monotonicity. To overcome these challenges, we have implemented an algorithm for Skew and Tail-heaviness Adjusted Removal of Outliers (STAR_outliers) that robustly removes univariate outliers from distributions with many different shape profiles, including extreme skew, extreme kurtosis, bimodality, and monotonicity. We show that STAR_outliers removes simulated outliers with greater recall and precision than several general algorithms, and it also models the outlier bounds of real data distributions with greater accuracy.Background Reliably removing univariate outliers from arbitrarily shaped distributions is a difficult task. Incorrectly assuming unimodality or overestimating tail heaviness fails to remove outliers, while underestimating tail heaviness incorrectly removes regular data from the tails. Skew often produces one heavy tail and one light tail, and we show that several sophisticated outlier removal algorithms often fail to remove outliers from the light tail. Multivariate outlier detection algorithms have recently become popular, but having tested PyOD's multivariate outlier removal algorithms, we found them to be inadequate for univariate outlier removal. They usually do not allow for univariate input, and they do not fit their distributions of outliership scores with a model on which an outlier threshold can be accurately established. Thus, there is a need for a flexible outlier removal algorithm that can model arbitrarily shaped univariate distributions.Results In order to effectively model arbitrarily shaped univariate distributions, we have combined several well-established algorithms into a new algorithm called STAR_outliers. STAR_outliers removes more simulated true outliers and fewer non-outliers than several other univariate algorithms. These include several normality-assuming outlier removal methods, PyOD's isolation forest (IF) outlier removal algorithm (ACM Transactions on Knowledge Discovery from Data (TKDD) 6:3, 2012) with default settings, and an IQR based algorithm by Verardi and Vermandele that removes outliers while accounting for skew and kurtosis (Verardi and Vermandele, Journal de la Société Française de Statistique 157:90-114, 2016). Since the IF algorithm's default model poorly fit the outliership scores, we also compared the isolation forest algorithm with a model that entails removing as many datapoints as STAR_outliers does in order of decreasing outliership scores. We also compared these algorithms on the publicly available 2018 National Health and Nutrition Examination Survey (NHANES) data by setting the outlier threshold to keep values falling within the main 99.3 percent of the fitted model's domain. We show that our STAR_outliers algorithm removes significantly closer to 0.7 percent of values from these features than other outlier removal methods on average.Conclusions STAR_outliers is an easily implemented python package for removing outliers that outperforms multiple commonly used methods of univariate outlier removal.

Improving Genetic Association Studies with a Novel Methodology that Unveils the Hidden Complexity of All-Cause Heart Failure.

Motivation: Genome-Wide Association Studies (GWAS) commonly assume phenotypic and genetic homogeneity that is not present in complex conditions. We designed Transformative Regression Analysis of Combined Effects (TRACE), a GWAS methodology that better accounts for clinical phenotype heterogeneity and identifies gene-by-environment (GxE) interactions. We demonstrated with UK Biobank (UKB) data that TRACE increased the variance explained in All-Cause Heart Failure (AHF) via the discovery of novel single nucleotide polymorphism (SNP) and SNP-by-environment (i.e. GxE) interaction associations. First, we transformed 312 AHF-related ICD10 codes (including AHF) into continuous low-dimensional features (i.e., latent phenotypes) for a more nuanced disease representation. Then, we ran a standard GWAS on our latent phenotypes to discover main effects and identified GxE interactions with target encoding. Genes near associated SNPs subsequently underwent enrichment analysis to explore potential functional mechanisms underlying associations. Latent phenotypes were regressed against their SNP hits and the estimated latent phenotype values were used to measure the amount of AHF variance explained. Results: Our method identified over 100 main GWAS effects that were consistent with prior studies and hundreds of novel gene-by-smoking interactions, which collectively accounted for approximately 10% of AHF variance. This represents an improvement over traditional GWAS whose results account for a negligible proportion of AHF variance. Enrichment analyses suggested that hundreds of miRNAs mediated the SNP effect on various AHF-related biological pathways. The TRACE framework can be applied to decode the genetics of other complex diseases. Availability: All code is available at https://github.com/EpistasisLab/latent_phenotype_project.

Polarization Topology at the Nominally Charged Domain Walls in Uniaxial Ferroelectrics.

Ferroelectric domain walls provide a fertile environment for novel materials physics. If a polarization discontinuity arises, it can drive a redistribution of electronic carriers and changes in band structure, which often result in emergent 2D conductivity. If such a discontinuity is not tolerated, then its amelioration usually involves the formation of complex topological patterns, such as flux-closure domains, dipolar vortices, skyrmions, merons, or Hopfions. The degrees of freedom required for the development of such patterns, in which dipolar rotation is a hallmark, are readily found in multiaxial ferroelectrics. In uniaxial ferroelectrics, where only two opposite polar orientations are possible, it has been assumed that discontinuities are unavoidable when antiparallel components of polarization meet. This perception has been borne out by the appearance of charged conducting domain walls in systems such as hexagonal manganites and lithium niobate. Here, experimental and theoretical investigations on lead germanate (Pb5 Ge3 O11 ) reveal that polar discontinuities can be obviated at head-to-head and tail-to-tail domain walls by mutual domain bifurcation along two different axes, creating a characteristic saddle-point domain wall morphology and associated novel dipolar topology, removing the need for screening charge accumulation and associated conductivity enhancement.

PMLB v1.0: an open-source dataset collection for benchmarking machine learning methods.

MOTIVATION: Novel machine learning and statistical modeling studies rely on standardized comparisons to existing methods using well-studied benchmark datasets. Few tools exist that provide rapid access to many of these datasets through a standardized, user-friendly interface that integrates well with popular data science workflows. RESULTS: This release of PMLB (Penn Machine Learning Benchmarks) provides the largest collection of diverse, public benchmark datasets for evaluating new machine learning and data science methods aggregated in one location. v1.0 introduces a number of critical improvements developed following discussions with the open-source community. AVAILABILITY AND IMPLEMENTATION: PMLB is available at https://github.com/EpistasisLab/pmlb. Python and R interfaces for PMLB can be installed through the Python Package Index and Comprehensive R Archive Network, respectively.

Intelligent Fusion Imaging Photonics for Real-Time Lighting Obstructions.

Dynamic detection in challenging lighting environments is essential for advancing intelligent robots and autonomous vehicles. Traditional vision systems are prone to severe lighting conditions in which rapid increases or decreases in contrast or saturation obscures objects, resulting in a loss of visibility. By incorporating intelligent optimization of polarization into vision systems using the iNC (integrated nanoscopic correction), we introduce an intelligent real-time fusion algorithm to address challenging and changing lighting conditions. Through real-time iterative feedback, we rapidly select polarizations, which is difficult to achieve with traditional methods. Fusion images were also dynamically reconstructed using pixel-based weights calculated in the intelligent polarization selection process. We showed that fused images by intelligent polarization selection reduced the mean-square error by two orders of magnitude to uncover subtle features of occluded objects. Our intelligent real-time fusion algorithm also achieved two orders of magnitude increase in time performance without compromising image quality. We expect intelligent fusion imaging photonics to play increasingly vital roles in the fields of next generation intelligent robots and autonomous vehicles.

Clinical stage molecule PT150 is a modulator of glucocorticoid and androgen receptors with antiviral activity against SARS-CoV-2.

PT150 is a clinical-stage molecule, taken orally, with a strong safety profile having completed Phase 1 and Phase 2 clinical trials for its original use as an antidepressant. It has an active IND for COVID-19. Antiviral activities have been found for PT150 and other members of its class in a variety of virus families; thus, it was now tested against SARS-CoV-2 in human bronchial epithelial lining cells and showed effective 90% inhibitory antiviral concentration (EC90) of 5.55 µM. PT150 is a member of an extended platform of novel glucocorticoid receptor (GR) and androgen receptor (AR) modulating molecules. In vivo, their predominant net effect is one of systemic glucocorticoid antagonism, but they also show direct downregulation of AR and minor GR agonism at the cellular level. We hypothesize that anti-SARS-CoV-2 activity depends in part on this AR downregulation through diminished TMPRSS2 expression and modulation of ACE2 activity. Given that hypercortisolemia is now suggested to be a significant co-factor for COVID-19 progression, we also postulate an additive role for its potent immunomodulatory effects through systemic antagonism of cortisol.

Clonal tracking in gene therapy patients reveals a diversity of human hematopoietic differentiation programs.

In gene therapy with human hematopoietic stem and progenitor cells (HSPCs), each gene-corrected cell and its progeny are marked in a unique way by the integrating vector. This feature enables lineages to be tracked by sampling blood cells and using DNA sequencing to identify the vector integration sites. Here, we studied 5 cell lineages (granulocytes, monocytes, T cells, B cells, and natural killer cells) in patients having undergone HSPC gene therapy for Wiskott-Aldrich syndrome or ß hemoglobinopathies. We found that the estimated minimum number of active, repopulating HSPCs (which ranged from 2000 to 50 000) was correlated with the number of HSPCs per kilogram infused. We sought to quantify the lineage output and dynamics of gene-modified clones; this is usually challenging because of sparse sampling of the various cell types during the analytical procedure, contamination during cell isolation, and different levels of vector marking in the various lineages. We therefore measured the residual contamination and corrected our statistical models accordingly to provide a rigorous analysis of the HSPC lineage output. A cluster analysis of the HSPC lineage output highlighted the existence of several stable, distinct differentiation programs, including myeloid-dominant, lymphoid-dominant, and balanced cell subsets. Our study evidenced the heterogeneous nature of the cell lineage output from HSPCs and provided methods for analyzing these complex data.

Lentiviral gene therapy for X-linked chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a rare inherited disorder of phagocytic cells1,2. We report the initial results of nine severely affected X-linked CGD (X-CGD) patients who received ex vivo autologous CD34+ hematopoietic stem and progenitor cell-based lentiviral gene therapy following myeloablative conditioning in first-in-human studies (trial registry nos. NCT02234934 and NCT01855685). The primary objectives were to assess the safety and evaluate the efficacy and stability of biochemical and functional reconstitution in the progeny of engrafted cells at 12 months. The secondary objectives included the evaluation of augmented immunity against bacterial and fungal infection, as well as assessment of hematopoietic stem cell transduction and engraftment. Two enrolled patients died within 3 months of treatment from pre-existing comorbidities. At 12 months, six of the seven surviving patients demonstrated stable vector copy numbers (0.4-1.8 copies per neutrophil) and the persistence of 16-46% oxidase-positive neutrophils. There was no molecular evidence of either clonal dysregulation or transgene silencing. Surviving patients have had no new CGD-related infections, and six have been able to discontinue CGD-related antibiotic prophylaxis. The primary objective was met in six of the nine patients at 12 months follow-up, suggesting that autologous gene therapy is a promising approach for CGD patients.

Copper Nanocubes for CO2 Reduction in Gas Diffusion Electrodes.

Electroreduction of CO2 represents a promising solution for addressing the global challenges in energy and sustainability. This reaction is highly sensitive to the surface structure of electrocatalysts and the local electrochemical environment. We have investigated the effect of Cu nanoparticle shape on the electrocatalysis of CO2 reduction by using gas-diffusion electrodes (GDEs) and flowing alkaline catholytes. Cu nanocubes of ∼70 nm in edge length are synthesized with {100} facets preferentially exposed on the surface. They are demonstrated to possess substantially enhanced catalytic activity and selectivity for CO2 reduction, compared to Cu nanospheres of similar particle sizes. The electrocatalytic performance was further found to be dependent on the concentration of electrolyte (KOH). The Cu nanocubes reach a Faradaic efficiency of 60% and a partial current density of 144 mA/cm2 toward ethylene (C2H4) production, with the catalytic enhancement being attributable to a combination of surface structure and electrolyte alkalinity effects.

Ensemble Effect in Bimetallic Electrocatalysts for CO2 Reduction.

Alloying is an important strategy for the design of catalytic materials beyond pure metals. The conventional alloy catalysts however lack precise control over the local atomic structures of active sites. Here we report on an investigation of the active-site ensemble effect in bimetallic Pd-Au electrocatalysts for CO2 reduction. A series of Pd@Au electrocatalysts are synthesized by decorating Au nanoparticles with Pd of controlled doses, giving rise to bimetallic surfaces containing Pd ensembles of various sizes. Their catalytic activity for electroreduction of CO2 to CO exhibits a nonlinear behavior in dependence of the Pd content, which is attributed to the variation of Pd ensemble size and the corresponding tuning of adsorption properties. Density functional theory calculations reveal that the Pd@Au electrocatalysts with atomically dispersed Pd sites possess lower energy barriers for activation of CO2 than pure Au and are also less poisoned by strongly binding *CO intermediates than pure Pd, with an intermediate ensemble size of active sites, such as Pd dimers, giving rise to the balance between these two rate-limiting factors and achieving the highest activity for CO2 reduction.

A quantitative approach for measuring the reservoir of latent HIV-1 proviruses.

A stable latent reservoir for HIV-1 in resting CD4+ T cells is the principal barrier to a cure1-3. Curative strategies that target the reservoir are being tested4,5 and require accurate, scalable reservoir assays. The reservoir was defined with quantitative viral outgrowth assays for cells that release infectious virus after one round of T cell activation1. However, these quantitative outgrowth assays and newer assays for cells that produce viral RNA after activation6 may underestimate the reservoir size because one round of activation does not induce all proviruses7. Many studies rely on simple assays based on polymerase chain reaction to detect proviral DNA regardless of transcriptional status, but the clinical relevance of these assays is unclear, as the vast majority of proviruses are defective7-9. Here we describe a more accurate method of measuring the HIV-1 reservoir that separately quantifies intact and defective proviruses. We show that the dynamics of cells that carry intact and defective proviruses are different in vitro and in vivo. These findings have implications for targeting the intact proviruses that are a barrier to curing HIV infection.

Long-term remission despite clonal expansion of replication-competent HIV-1 isolates.

Clonal expansion of T cells harboring replication-competent virus has recently been demonstrated in patients on suppressive antiretroviral therapy (ART) regimens. However, there has not been direct evidence of this phenomenon in settings of natural control, including in posttreatment controllers who maintain control of viral replication after treatment when ART is discontinued. We present a case of an individual who has had undetectable viral loads for more than 15 years following the cessation of ART. Using near-full-genome sequence analysis, we demonstrate that 9 of 12 replication-competent isolates cultured from this subject were identical and that this identity was maintained 6 months later. A similar pattern of replication-competent virus clonality was seen in a treatment-naive HLA-B*57 elite controller. In both cases, we show that CD8+ T cells are capable of suppressing the replication of the clonally expanded viruses in vitro. Our data suggest that, while clonal expansion of replication-competent virus can present a barrier to viral eradication, these viral isolates remain susceptible to HIV-specific immune responses and can be controlled in patients with long-term suppression of viral replication.

A Recurrent Silent Mutation Implicates fecA in Ethanol Tolerance by Escherichia coli.

BACKGROUND: An issue associated with efficient bioethanol production is the fact that the desired product is toxic to the biocatalyst. Among other effects, ethanol has previously been found to influence the membrane of E. coli in a dose-dependent manner and induce changes in the lipid composition of the plasma membrane. We describe here the characterization of a collection of ethanol-tolerant strains derived from the ethanologenic Escherichia coli strain FBR5. RESULTS: Membrane permeability assays indicate that many of the strains in the collection have alterations in membrane permeability and/or responsiveness of the membrane to environmental changes such as temperature shifts or ethanol exposure. However, analysis of the strains by gas chromatography and mass spectrometry revealed no qualitative changes in the acyl chain composition of membrane lipids in response to ethanol or temperature. To determine whether these strains contain any mutations that might contribute to ethanol tolerance or changes in membrane permeability, we sequenced the entire genome of each strain. Unexpectedly, none of the strains displayed mutations in genes known to control membrane lipid synthesis, and a few strains carried no mutations at all. Interestingly, we found that four independently-isolated strains acquired an identical C → A (V244 V) silent mutation in the ferric citrate transporter gene fecA. Further, we demonstrated that either a deletion of fecA or over-expression of fecA can confer increased ethanol survival, suggesting that any misregulation of fecA expression affects the cellular response to ethanol. CONCLUSIONS: The fact that no mutations were observed in several ethanol-tolerant strains suggested that epigenetic mechanisms play a role in E. coli ethanol tolerance and membrane permeability. Our data also represent the first direct phenotypic evidence that the fecA gene plays a role in ethanol tolerance. We propose that the recurring silent mutation may exert an effect on phenotype by altering RNA-mediated regulation of fecA expression.

Development of mirror pain following trigeminal nerve injury: a case report and review of neuropathic mechanisms.

Following injury to a peripheral nerve, patients may complain of pain over the distribution of the same contralateral nerve, a phenomenon referred to as contralateral pain or mirror pain (MP). Symptoms of MP usually begin after the neuropathic pain from the original nerve injury has become chronic. Chronic neuropathic pain can lead to sensitization and spread of pain. Because the diagnosis of MP can be missed, patients may undergo multiple treatment procedures that prove to be ineffective in relieving the pain. This article presents a case of MP that appeared approximately 20 months following inferior alveolar nerve injury that occurred during placement of a dental implant in the region of the first molar. Acutely painful nerve injuries must be aggressively treated to prevent changeover to a chronic pain state characterized by sensitization and spread of pain beyond the initial injury. Consequently, clinicians need to begin effective, early pain management to prevent the changeover to chronic pain that has become centralized and refractive to treatment.

Insulin resistance and adipose-derived hormones in young men with untreated obstructive sleep apnea.

PURPOSE: Obstructive sleep apnea (OSA) increases the risk for insulin resistance (IR). The mechanisms that link the two are not clear and are frequently confounded by obesity. OSA is associated with alterations in adipose-derived hormones (adipokines) that increase IR; however, previous studies have focused on middle-aged and older adults. The objective of this study was to determine if IR and alterations in adipokines exist in young men with OSA, independent of obesity. METHODS: Subjects were assigned into the following groups based on body mass index and presence of OSA: obese with OSA (OSA, n = 12), obese without OSA (NOSA, n = 18), and normal weight without OSA (CON, n = 15). Fasting blood was obtained for batch analysis of biomarkers of IR. The homeostasis model assessment (HOMA) method was used to assess IR. RESULTS: HOMA and leptin were higher in the OSA group than the CON group. There were no differences in insulin, tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) between the OSA and NOSA groups. Adiponectin was lower in the OSA group vs. NOSA and CON; however, when controlled for central abdominal fat (CAF), the difference was nullified. When controlled for total body adiposity, however, CAF was 24 % higher in the subjects with OSA vs. subjects without OSA. CONCLUSIONS: These findings suggest that excess CAF in young men with OSA may contribute to risk for type 2 diabetes indirectly by a degree that would otherwise not be reached through obesity, although further research is needed.

Synthesis of epitaxial metal oxide nanocrystals via a phase separation approach.

Perovskite phase instability of BiMnO3 has been exploited to synthesize epitaxial metal oxide magnetic nanocrystals. Thin film processing conditions are tuned to promote the breakdown of the perovskite precursor into Bi2O3 matrix and magnetic manganese oxide islands. Subsequent cooling in vacuum ensures complete volatization of the Bi2O3, thus leaving behind an array of self-assembled magnetic Mn3O4 nanostructures. Both shape and size can be systematically controlled by the ambient oxygen environments and deposition time. As such, this approach can be extended to any other Bi-based complex ternary oxide system as it primarily hinges on the breakdown of parent Bi-based precursor and subsequent Bi2O3 volatization.

All-linear time reversal by a dynamic artificial crystal.

The time reversal of pulsed signals or propagating wave packets has long been recognized to have profound scientific and technological significance. Until now, all experimentally verified time-reversal mechanisms have been reliant upon nonlinear phenomena such as four-wave mixing. In this paper, we report the experimental realization of all-linear time reversal. The time-reversal mechanism we propose is based on the dynamic control of an artificial crystal structure, and is demonstrated in a spin-wave system using a dynamic magnonic crystal. The crystal is switched from an homogeneous state to one in which its properties vary with spatial period a, while a propagating wave packet is inside. As a result, a linear coupling between wave components with wave vectors k≈π/a and k'=k-2π/a≈-π/a is produced, which leads to spectral inversion, and thus to the formation of a time-reversed wave packet. The reversal mechanism is entirely general and so applicable to artificial crystal systems of any physical nature.

Early evidence of increased risk for metabolic syndrome in young men with latent obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is characterized by a repetitive collapse of the upper airway during sleep and may affect as many as 1 in 5 adults. Although OSA appears to increase risk for metabolic syndrome in middle-aged adults, no data currently exist in a younger, preclinical cohort. METHODS: Forty-five sedentary young men: 12 overweight with OSA (OSA), 18 overweight without OSA (NOSA), and 15 normal-weight without OSA (CON). Respiratory distress index (RDI) was determined using an at-home, unsupervised, portable polygraphy device. Total and subcutaneous abdominal fat (SAF) were quantified using dual-energy X-ray absorptiometry (DXA). Blood pressure was obtained manually via auscultation. Fasting triglycerides, glucose, and high-density lipoprotein cholesterol (HDL-C) concentrations were analyzed from whole blood using a commercial lipid profile kit. RESULTS: The OSA group had 25% more SAF than the NOSA group (P < 0.05) and higher triglycerides (136.7 +/- 21.3 mg/dL versus 92.2 +/- 7.5, P < 0.05). RDI was directly related to fasting triglycerides (R = 0.32, P < 0.05) after controlling for SAF. The number of metabolic syndrome components was directly correlated to indices of adiposity, but not RDI. Using multiple linear regression analysis, triglycerides were the only independent predictor of RDI. CONCLUSIONS: Results from this study demonstrate that unique physiologic and anthropometric abnormalities exist in young men with occult OSA, beyond those that are seen in uncomplicated obesity. These findings may indicate early pathogenesis of metabolic syndrome in these young men.

Altered ventilatory responses to exercise testing in young adult men with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is a disorder characterized by repetitive obstructions of the upper airway. Individuals with OSA experience intermittent hypoxia, hypercapnia, and arousals during sleep, resulting in increased sympathetic activation. Chemoreflex activation, arising from the resultant oscillatory disturbances in blood gases from OSA, exerts control over ventilation, and may induce increases in sympathetic vasoconstriction, contributing to increased long-term risks for hypertension (HTN) and cardiovascular disease (CVD). METHODS: To evaluate whether OSA elicits exaggerated ventilatory responses to exercise in young men, 14 overweight men with OSA and 16 overweight men without OSA performed maximal ramping cycle ergometer exercise tests. Oxygen consumption (VO(2)), ventilation, (V(E)), ventilatory equivalents for oxygen (V(E)/VO(2)) and carbon dioxide (V(E)/VCO(2)), and V(E)/VCO(2) slope were measured. RESULTS: The VO(2) response to exercise did not differ between groups. The V(E), V(E)/VCO(2), V(E)/VO(2) were higher (p< 0.05, 0.002, and p<0.02, respectively) in the OSA group across all workloads. The V(E)/VCO(2) slope was greater in the OSA group (p<0.05). The V(E)/VCO(2) slope and AHI were significantly correlated (r=0.56, p<0.03). Thus, young, overweight men with OSA exhibit increased ventilatory responses to exercise when compared to overweight controls. This may reflect alterations in chemoreflex sensitivity, and contribute to increased sympathetic drive and HTN risk.

Potential clinical use of cardiopulmonary exercise testing in obstructive sleep apnea hypopnea syndrome.

There is growing evidence linking obstructive sleep apnea hypopnea syndrome (OSAHS) with multiple cardiovascular and metabolic diseases. Exercise testing is generally available and routinely used to provide valuable information on cardiopulmonary function in healthy and diseased populations. This review summarizes and integrates recent findings on exercise testing in OSAHS and discusses the potential mechanisms that may contribute to the responses that seem to differentiate these patients from apparently healthy subjects and patients with other cardiopulmonary diseases. Although exercise testing is widely used in the evaluation and diagnosis of coronary artery disease patients, recent studies showed distinctive cardiopulmonary responses in OSAHS that raise the possibility of similar applications in this disorder, as well. Several studies illustrated in this review found that OSAHS patients have a reduced exercise capacity, as shown by low peak oxygen uptake achieved. Also, their exercise HR response was reported as significantly lower than in healthy peers, suggesting chronotropic incompetence. Exercise blood pressure response were atypical as well. OSAHS patients had increased systolic and diastolic BP during exercise and a persistently elevated systolic BP during the early post-exercise recovery period. Possible explanations for these responses include cardiac dysfunction, impaired muscle metabolism, chronic sympathetic over-activation, and endothelial dysfunction. Early identification of OSAHS using cardiopulmonary exercise testing (CPXT) shows promise for selecting patients at risk for this disorder in the clinical setting. A uniform definition and measurement of OSAHS together with more rigorous trials are necessary to establish the utility of exercise responses in clinical settings.