KR158 spheres harboring slow-cycling cells recapitulate GBM features in an immunocompetent system.

Glioblastoma (GBM) poses a significant challenge in clinical oncology due to its aggressive nature, heterogeneity, and resistance to therapies. Cancer stem cells (CSCs) play a critical role in GBM, particularly in treatment-resistance and tumor relapse, emphasizing the need to comprehend the mechanisms regulating these cells. Also, their multifaceted contributions to the tumor-microenvironment (TME) underline their significance, driven by their unique properties. This study aimed to characterize glioblastoma stem cells (GSCs), specifically slow-cycling cells (SCCs), in an immunocompetent murine GBM model to explore their similarities with their human counterparts. Using the KR158 mouse model, we confirmed that SCCs isolated from this model exhibited key traits and functional properties akin to human SCCs. KR158 murine SCCs, expanded in the gliomasphere assay, demonstrated sphere forming ability, self-renewing capacity, positive tumorigenicity, enhanced stemness and resistance to chemotherapy. Together, our findings validate the KR158 murine model as a framework to investigate GSCs and SCCs in GBM-pathology, and explore specifically the SCC-immune system communications, understand their role in disease progression, and evaluate the effect of therapeutic strategies targeting these specific connections.

Increased odds for COVID-19 infection among individuals with periodontal disease.

OBJECTIVES: Periodontal disease has been linked to multiple systemic conditions, but the relationship with COVID-19 still needs to be elucidated. We hypothesized that periodontal disease may be associated with COVID-19 infection. MATERIALS AND METHODS: This study utilized cross-sectional data to establish the strength of the association between periodontal disease and COVID-19 infection. The University of Florida Health Center's i2b2 patient's registry was used to generate patient counts through ICD-10 diagnostic codes. Univariate descriptive statistics of the patient population and logistic regression to estimate odds ratios of associations between periodontal disease and COVID-19 infection were used for analysis. RESULTS: Patients with periodontal disease were 4.4 times more likely to be positively diagnosed with COVID-19 than patients without PD. Associations remained similar and robust (P value < 0.0001) after adjustment for age (OR = 4.34; 95% CI, 3.68-5.09), gender (OR = 4.46; 95% CI, 3.79-5.23), and smoking status (OR = 4.77; 95% CI, 4.04-5.59). Associations were smaller but remained robust (P value < 0.0001) after adjusting for race (OR = 2.83; 95% CI, 2.40-3.32), obesity (OR = 2.53; 95% CI, 2.14-2.98), diabetes (OR = 3.32; 95% CI, 2.81-3.90), and cardiovascular disease (OR = 2.68; 95% CI, 2.27-3.14). CONCLUSIONS: Periodontal disease is significantly associated with increased odds for COVID-19 infection. CLINICAL RELEVANCE: With the caveat of a cross-sectional study design, these results suggest that periodontal disease may increase the odds for COVID-19 infection.

Variant APOL1 protein in plasma associates with larger particles in humans and mouse models of kidney injury.

BACKGROUND: Genetic variants in apolipoprotein L1 (APOL1), a protein that protects humans from infection with African trypanosomes, explain a substantial proportion of the excess risk of chronic kidney disease affecting individuals with sub-Saharan ancestry. The mechanisms by which risk variants damage kidney cells remain incompletely understood. In preclinical models, APOL1 expressed in podocytes can lead to significant kidney injury. In humans, studies in kidney transplant suggest that the effects of APOL1 variants are predominantly driven by donor genotype. Less attention has been paid to a possible role for circulating APOL1 in kidney injury. METHODS: Using liquid chromatography-tandem mass spectrometry, the concentrations of APOL1 were measured in plasma and urine from participants in the Seattle Kidney Study. Asymmetric flow field-flow fractionation was used to evaluate the size of APOL1-containing lipoprotein particles in plasma. Transgenic mice that express wild-type or risk variant APOL1 from an albumin promoter were treated to cause kidney injury and evaluated for renal disease and pathology. RESULTS: In human participants, urine concentrations of APOL1 were correlated with plasma concentrations and reduced kidney function. Risk variant APOL1 was enriched in larger particles. In mice, circulating risk variant APOL1-G1 promoted kidney damage and reduced podocyte density without renal expression of APOL1. CONCLUSIONS: These results suggest that plasma APOL1 is dynamic and contributes to the progression of kidney disease in humans, which may have implications for treatment of APOL1-associated kidney disease and for kidney transplantation.

Integrated Quantitative Targeted Lipidomics and Proteomics Reveal Unique Fingerprints of Multiple Metabolic Conditions.

Aberrations in lipid and lipoprotein metabolic pathways can lead to numerous diseases, including cardiovascular disease, diabetes, neurological disorders, and cancer. The integration of quantitative lipid and lipoprotein profiling of human plasma may provide a powerful approach to inform early disease diagnosis and prevention. In this study, we leveraged data-driven quantitative targeted lipidomics and proteomics to identify specific molecular changes associated with different metabolic risk categories, including hyperlipidemic, hypercholesterolemic, hypertriglyceridemic, hyperglycemic, and normolipidemic conditions. Based on the quantitative characterization of serum samples from 146 individuals, we have determined individual lipid species and proteins that were significantly up- or down-regulated relative to the normolipidemic group. Then, we established protein-lipid topological networks for each metabolic category and linked dysregulated proteins and lipids with defined metabolic pathways. To evaluate the differentiating power of integrated lipidomics and proteomics data, we have built an artificial neural network model that simultaneously and accurately categorized the samples from each metabolic risk category based on the determined lipidomics and proteomics profiles. Together, our findings provide new insights into molecular changes associated with metabolic risk conditions, suggest new condition-specific associations between apolipoproteins and lipids, and may inform new biomarker discovery in lipid metabolism-associated disorders.

Deleterious mtDNA mutations are common in mature oocytes.

Heritable mitochondrial DNA (mtDNA) mutations are common, yet only a few recurring pathogenic mtDNA variants account for the majority of known familial cases in humans. Purifying selection in the female germline is thought to be responsible for the elimination of most harmful mtDNA mutations during oogenesis. Here we show that deleterious mtDNA mutations are abundant in ovulated mature mouse oocytes and preimplantation embryos recovered from PolG mutator females but not in their live offspring. This implies that purifying selection acts not in the maternal germline per se, but during post-implantation development. We further show that oocyte mtDNA mutations can be captured and stably maintained in embryonic stem cells and then reintroduced into chimeras, thereby allowing examination of the effects of specific mutations on fetal and postnatal development.

Parameterizing a dynamic influenza model using longitudinal versus age-stratified case notifications yields different predictions of vaccine impacts.

Dynamic transmission models of influenza are sometimes used in decision-making to identify which vaccination strategies might best reduce influenza-associated health burdens. Our goal was to use laboratory confirmed influenza cases to fit model parameters in an age-structured, two-type (influenza A/B) dynamic model of influenza. We compared the fitted model under two fitting methodologies: using longitudinal weekly case notification data versus using cross-sectional age-stratified cumulative case notification data. The longitudinal data came from a Canadian province (Ontario)whereasthecross-sectionaldatacamefromthenationallevel(allofCanada). Wefindthatthe longitudinal fitting method provides best fitting parameter sets that have a higher variance between the respective parameters in each set than the cross-sectional cumulative case method. Model predictions-particularly for influenza A-are very different for the two fitting methodologies under hypothetical vaccination scenarios that expand coverage in either younger age classes or older age classes: the cross-sectional method predicts much larger decreases in total cases under expanded vaccine coverage than the longitudinal method. Also, the longitudinal method predicts that vaccinating younger age groups yields greater declines in total cases than vaccinating older age groups, whereas the cross- sectional method predicts the opposite. We conclude that model predictions of vaccination impacts under different strategies may differ at national versus provincial levels. Finally, we discuss whether usinglongitudinalversuscross-sectionaldatainmodelfittingmaygeneratefurtherdifferencesinmodel predictions (above and beyond population-specific differences) and how such a hypothesis could be tested in future studies.

Development and Validation of a Novel Risk Score for Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction.

BACKGROUND: Primary percutaneous coronary intervention (PPCI) is the default treatment for patients with ST elevation myocardial infarction (STEMI) and carries a higher risk of adverse outcomes when compared with elective and urgent PCI. Conventional PCI risk scores tend to be complex and may underestimate the risk associated with PPCI due to under-representation of patients with STEMI in their datasets. This study aimed to develop a simple, practical and contemporary risk model to provide risk stratification in PPCI. METHODS: Demographic, clinical and outcome data were collected for all patients who underwent PPCI between January 2009 and October 2013 at the Northern General Hospital, Sheffield. Multiple regression analysis was used to identify independent predictors of mortality and to construct a risk model. This model was then separately validated on an internal and external dataset. RESULTS: The derivation cohort included 2870 patients with a 30-day mortality of 5.1% (145 patients). Only four variables were required to predict 30-day mortality: age [OR:1.047, 95% CI:1.031-1.063], call-to-balloon (CTB) time [OR:1.829, 95% CI:1.198-2.791], cardiogenic shock [OR:13.886, 95% CI:8.284-23.275] and congestive heart failure [OR:3.169, 95% CI:1.420-7.072]. Internal validation was performed in 693 patients and external validation in 660 patients undergoing PPCI. Our model showed excellent discrimination on ROC-curve analysis (C-Stat = 0.87 internal and 0.86, external), and excellent calibration on Hosmer-Lemeshow testing (p = 0.37 internal, 0.55 external). CONCLUSIONS: We have developed a bedside risk model which can predict 30-day mortality after PPCI using only four variables: age, CTB time, congestive heart failure and shock.

Two photon spectroscopy and microscopy of the fluorescent flavoprotein, iLOV.

LOV-domains are ubiquitous photosensory proteins that are commonly re-engineered to serve as powerful and versatile fluorescent proteins and optogenetic tools. The photoactive, flavin chromophore, however, is excited using short wavelengths of light in the blue and UV regions, which have limited penetration into biological samples and can cause photodamage. Here, we have used non-linear spectroscopy and microscopy of the fluorescent protein, iLOV, to reveal that functional variants of LOV can be activated to great effect by two non-resonant photons of lower energy, near infrared light, not only in solution but also in biological samples. The two photon cross section of iLOV has a significantly blue-shifted S0 → S1 transition compared with the one photon absorption spectrum, suggesting preferential population of excited vibronic states. It is highly likely, therefore, that the two photon absorption wavelength of engineered, LOV-based tools is tuneable. We also demonstrate for the first time two photon imaging using iLOV in human epithelial kidney cells. Consequently, two photon absorption by engineered, flavin-based bio-molecular tools can enable non-invasive activation with high depth resolution and the potential for not only improved image clarity but also enhanced spatiotemporal control for optogenetic applications.

Core lipid, surface lipid and apolipoprotein composition analysis of lipoprotein particles as a function of particle size in one workflow integrating asymmetric flow field-flow fractionation and liquid chromatography-tandem mass spectrometry.

Lipoproteins are complex molecular assemblies that are key participants in the intricate cascade of extracellular lipid metabolism with important consequences in the formation of atherosclerotic lesions and the development of cardiovascular disease. Multiplexed mass spectrometry (MS) techniques have substantially improved the ability to characterize the composition of lipoproteins. However, these advanced MS techniques are limited by traditional pre-analytical fractionation techniques that compromise the structural integrity of lipoprotein particles during separation from serum or plasma. In this work, we applied a highly effective and gentle hydrodynamic size based fractionation technique, asymmetric flow field-flow fractionation (AF4), and integrated it into a comprehensive tandem mass spectrometry based workflow that was used for the measurement of apolipoproteins (apos A-I, A-II, A-IV, B, C-I, C-II, C-III and E), free cholesterol (FC), cholesterol esters (CE), triglycerides (TG), and phospholipids (PL) (phosphatidylcholine (PC), sphingomyelin (SM), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and lysophosphatidylcholine (LPC)). Hydrodynamic size in each of 40 size fractions separated by AF4 was measured by dynamic light scattering. Measuring all major lipids and apolipoproteins in each size fraction and in the whole serum, using total of 0.1 ml, allowed the volumetric calculation of lipoprotein particle numbers and expression of composition in molar analyte per particle number ratios. Measurements in 110 serum samples showed substantive differences between size fractions of HDL and LDL. Lipoprotein composition within size fractions was expressed in molar ratios of analytes (A-I/A-II, C-II/C-I, C-II/C-III. E/C-III, FC/PL, SM/PL, PE/PL, and PI/PL), showing differences in sample categories with combinations of normal and high levels of Total-C and/or Total-TG. The agreement with previous studies indirectly validates the AF4-LC-MS/MS approach and demonstrates the potential of this workflow for characterization of lipoprotein composition in clinical studies using small volumes of archived frozen samples.

Development and validation of a clinical risk score to predict mortality after percutaneous coronary intervention.

OBJECTIVE: To develop and validate a contemporary clinical risk score to predict mortality after percutaneous coronary intervention (PCI). METHODS: Using data collected from patients undergoing PCI at the South Yorkshire Cardiothoracic Centre, Sheffield, UK, between January 2007 and September 2013, a risk score was developed to predict mortality. Logistic regression was used to evaluate the effect of each variable upon 30-day mortality. A backwards stepwise logistic regression model was then used to build a predictive model. The results were validated both internally and externally with data from Manchester Royal Infirmary, UK. 30-Day mortality status was determined from the UK Office of National Statistics. RESULTS: The development data set comprised 6522 patients from Sheffield. Five risk factors, including cardiogenic shock, procedural urgency, history of renal disease, diabetes mellitus and age, were statistically significant to predict 30-day mortality. The risk score was validated internally on a further 3290 patients from Sheffield and externally on 3230 patients from Manchester. The discrimination of the model was high in the development (C-statistic=0.82, 95% CI 0.79 to 0.85), internal (C-statistic=0.81, 95% CI 0.76 to 0.86) and external (C statistics=0.90, 95% CI 0.87 to 0.93) cohorts. There was no significant difference between observed and predicted mortality in any group. CONCLUSION: This contemporary risk score reliably predicts 30-day mortality after PCI using a small number of clinical variables obtainable prior to the procedure, without knowledge of the coronary anatomy.

Long-Term Efficacy of GMP Grade Xeno-Free hESC-Derived RPE Cells Following Transplantation.

PURPOSE: Retinal pigment epithelium (RPE) dysfunction underlies the retinal degenerative process in age-related macular degeneration (AMD), and thus RPE cell replacement provides an optimal treatment target. We characterized longitudinally the efficacy of RPE cells derived under xeno-free conditions from clinical and xeno-free grade human embryonic stem cells (OpRegen) following transplantation into the subretinal space of Royal College of Surgeons (RCS) rats. METHODS: Postnatal (P) day 20 to 25 RCS rats (n = 242) received a single subretinal injection of 25,000 (low)-, 100,000 (mid)-, or 200,000 (high)-dose xeno-free RPE cells. BSS+ (balanced salt solution) (vehicle) and unoperated eyes served as controls. Optomotor tracking (OKT) behavior was used to quantify functional efficacy. Histology and immunohistochemistry were used to evaluate photoreceptor rescue and transplanted cell survival at 60, 100, 150, and 200 days of age. RESULTS: OKT was rescued in a dose-dependent manner. Outer nuclear layer (ONL) was significantly thicker in cell-treated eyes than controls up to P150. Transplanted RPE cells were identified in both the subretinal space and integrated into the host RPE monolayer in animals of all age groups, and often contained internalized photoreceptor outer segments. No pathology was observed. CONCLUSIONS: OpRegen RPE cells survived, rescued visual function, preserved rod and cone photoreceptors long-term in the RCS rat. Thus, these data support the use of OpRegen RPE cells for the treatment of human RPE cell disorders including AMD. TRANSLATIONAL RELEVANCE: Our novel xeno-free RPE cells minimize concerns of animal derived contaminants while providing a promising prospective therapy to the diseased retina.

Long-term Characterization of Retinal Degeneration in Royal College of Surgeons Rats Using Spectral-Domain Optical Coherence Tomography.

Purpose: Prospective treatments for age-related macular degeneration and inherited retinal degenerations are commonly evaluated in the Royal College of Surgeons (RCS) rat before translation into clinical application. Historically, retinal thickness obtained through postmortem anatomic assessments has been a key outcome measure; however, utility of this measurement is limited because it precludes the ability to perform longitudinal studies. To overcome this limitation, the present study was designed to provide a baseline longitudinal quantification of retinal thickness in the RCS rat by using spectral-domain optical coherence tomography (SD-OCT). Methods: Horizontal and vertical linear SD-OCT scans centered on the optic nerve were captured from Long-Evans control rats at P30, P60, P90 and from RCS rats between P17 and P90. Total retina (TR), outer nuclear layer+ (ONL+), inner nuclear layer (INL), and retinal pigment epithelium (RPE) thicknesses were quantified. Histologic sections of RCS retina obtained from P21 to P60 were compared to SD-OCT images. Results: In RCS rats, TR and ONL+ thickness decreased significantly as compared to Long-Evans controls. Changes in INL and RPE thickness were not significantly different between control and RCS retinas. From P30 to P90 a subretinal hyperreflective layer (HRL) was observed and quantified in RCS rats. After correlation with histology, the HRL was identified as disorganized outer segments and the location of accumulated debris. Conclusions: Retinal layer thickness can be quantified longitudinally throughout the course of retinal degeneration in the RCS rat by using SD-OCT. Thickness measurements obtained with SD-OCT were consistent with previous anatomic thickness assessments. This study provides baseline data for future longitudinal assessment of therapeutic agents in the RCS rat.

High throughput quantification of apolipoproteins A-I and B-100 by isotope dilution MS targeting fast trypsin releasable peptides without reduction and alkylation.

PURPOSE: Apolipoprotein A-I (ApoA-I) and apolipoprotein B-100 (ApoB-100) are amphipathic proteins that are strong predictors of cardiovascular disease risk. The traceable calibration of apolipoprotein assays is a persistent challenge, especially for ApoB-100, which cannot be solubilized in purified form. EXPERIMENTAL DESIGN: A simultaneous quantitation method for ApoA-I and ApoB-100 was developed using tryptic digestion without predigestion reduction and alkylation, followed by LC separation coupled with isotope dilution MS analysis. The accuracy of the method was assured by selecting structurally exposed signature peptides, optimal choice of detergent, protein:enzyme ratio, and incubation time. Peptide calibrators were value assigned by isobaric tagging isotope dilution MS amino acid analysis. RESULTS: The method reproducibility was validated in technical repeats of three serum samples, giving 2-3% intraday CVs (N = 5) and <7% interday CVs (N = 21). The repeated analysis of interlaboratory harmonization standards showed -1% difference for ApoA-I and -12% for ApoB-100 relative to the assigned value. The applicability of the method was demonstrated by repeated analysis of 24 patient samples with a wide range of total cholesterol and triglyceride levels. CONCLUSIONS AND CLINICAL RELEVANCE: The method is applicable for simultaneous analysis of ApoA-I and ApoB-100 in patient samples, and for characterization of serum pool calibrators for other analytical platforms.

On-column trypsin digestion coupled with LC-MS/MS for quantification of apolipoproteins.

Apolipoproteins measured in plasma or serum are potential biomarkers for assessing metabolic irregularities that are associated with the development of cardiovascular disease (CVD). LC-MS/MS allows quantitative measurement of multiple apolipoproteins in the same sample run. However, the accuracy and precision of the LC-MS/MS measurement depends on the reproducibility of the enzymatic protein digestion step. With the application of an immobilized enzyme reactor (IMER), the reproducibility of the trypsin digestion can be controlled with high precision via flow rate, column volume and temperature. In this report, we demonstrate the application of an integrated IMER-LC-MS/MS platform for the simultaneous quantitative analysis of eight apolipoproteins. Using a dilution series of a characterized serum pool as calibrator, the method was validated by repeated analysis of pooled sera and individual serum samples with a wide range of lipid profiles, all showing intra-assay CV<4.4% and inter-assay CV<8%. In addition, the method was compared with traditional homogeneous digestion coupled LC-MS/MS for the quantification of apoA-I and apoB-100. Applied in large scale human population studies, this method can serve the translation of a wider panel of apolipoprotein biomarkers from research to clinical application. SIGNIFICANCE: Currently, the translation of apolipoprotein biomarkers to clinical application is impaired because of the high cost of large cohort studies using traditional single-analyte immunoassays. The application of on-line tryptic digestion coupled with LC-MS/MS analysis is an effective way to address this problem. In this work we demonstrate a high throughput, multiplexed, automated proteomics workflow for the simultaneous analysis of multiple proteins.

The impacts of simultaneous disease intervention decisions on epidemic outcomes.

Mathematical models of the interplay between disease dynamics and human behavioural dynamics can improve our understanding of how diseases spread when individuals adapt their behaviour in response to an epidemic. Accounting for behavioural mechanisms that determine uptake of infectious disease interventions such as vaccination and non-pharmaceutical interventions (NPIs) can significantly alter predicted health outcomes in a population. However, most previous approaches that model interactions between human behaviour and disease dynamics have modelled behaviour of these two interventions separately. Here, we develop and analyze an agent based network model to gain insights into how behaviour toward both interventions interact adaptively with disease dynamics (and therefore, indirectly, with one another) during the course of a single epidemic where an SIRV infection spreads through a contact network. In the model, individuals decide to become vaccinated and/or practice NPIs based on perceived infection prevalence (locally or globally) and on what other individuals in the network are doing. We find that introducing adaptive NPI behaviour lowers vaccine uptake on account of behavioural feedbacks, and also decreases epidemic final size. When transmission rates are low, NPIs alone are as effective in reducing epidemic final size as NPIs and vaccination combined. Also, NPIs can compensate for delays in vaccine availability by hindering early disease spread, decreasing epidemic size significantly compared to the case where NPI behaviour does not adapt to mitigate early surges in infection prevalence. We also find that including adaptive NPI behaviour strongly mitigates the vaccine behavioural feedbacks that would otherwise result in higher vaccine uptake at lower vaccine efficacy as predicted by most previous models, and the same feedbacks cause epidemic final size to remain approximately constant across a broad range of values for vaccine efficacy. Finally, when individuals use local information about others' behaviour and infection prevalence, instead of population-level information, infection is controlled more efficiently through ring vaccination, and this is reflected in the time evolution of pair correlations on the network. This model shows that accounting for both adaptive NPI behaviour and adaptive vaccinating behaviour regarding social effects and infection prevalence can result in qualitatively different predictions than if only one type of adaptive behaviour is modelled.

Operation Windshield and the simplification of emergency management.

Large, complex, multi-stakeholder exercises are the culmination of years of gradual progression through a comprehensive training and exercise programme. Exercises intended to validate training, refine procedures and test processes initially tested in isolation are combined to ensure seamless response and coordination during actual crises. The challenges of integrating timely and accurate situational awareness from an array of sources, including response agencies, municipal departments, partner agencies and the public, on an ever-growing range of media platforms, increase information management complexity in emergencies. Considering that many municipal emergency operations centre roles are filled by staff whose day jobs have little to do with crisis management, there is a need to simplify emergency management and make it more intuitive. North Shore Emergency Management has accepted the challenge of making emergency management less onerous to occasional practitioners through a series of initiatives aimed to build competence and confidence by making processes easier to use as well as by introducing technical tools that can simplify processes and enhance efficiencies. These efforts culminated in the full-scale earthquake exercise, Operation Windshield, which preceded the 2015 Emergency Preparedness and Business Continuity Conference in Vancouver, British Columbia.

Room for Improvement in Nutrition Knowledge and Dietary Intake of Male Football (Soccer) Players in Australia.

Athletes require sufficient nutrition knowledge and skills to enable appropriate selection and consumption of food and fluids to meet their health, body composition, and performance needs. This article reports the nutrition knowledge and dietary habits of male football (soccer) players in Australia. Players age 18 years and older were recruited from 1 A-League club (professional) and 4 National Premier League clubs (semiprofessional). No significant difference in general nutrition knowledge (GNK; 54.1% ± 13.4%; 56.8% ± 11.7%; M ± SD), t(71) = -0.91, p = .37, or sports nutrition knowledge (SNK; 56.9% ± 15.5%; 61.3% ± 15.9%), t(71) = -1.16, p = .25) were noted between professional (n = 29) and semiprofessional (n = 44) players. In general, players lacked knowledge in regard to food sources and types of fat. Although nutrition knowledge varied widely among players (24.6-82.8% correct responses), those who had recently studied nutrition answered significantly more items correctly than those who reported no recent formal nutrition education (62.6% ± 11.9%; 54.0% ± 11.4%), t(67) = 2.88, p = .005). Analysis of 3-day estimated food diaries revealed both professionals (n = 10) and semiprofessionals (n = 31) consumed on average less carbohydrate (3.5 ± 0.8 gC/kg; 3.9 ± 1.8 gC/kg) per day than football-specific recommendations (FIFA Medical and Assessment Research Centre [F-MARC]: 5-10 gC/kg). There was a moderate, positive correlation between SNK and carbohydrate intake (n = 41, ρ = 0.32, p = .04), indicating that players who exhibited greater SNK had higher carbohydrate intakes. On the basis of these findings, male football players in Australia would benefit from nutrition education targeting carbohydrate and fat in an attempt to improve nutrition knowledge and dietary practices.

Coupled disease-behavior dynamics on complex networks: A review.

It is increasingly recognized that a key component of successful infection control efforts is understanding the complex, two-way interaction between disease dynamics and human behavioral and social dynamics. Human behavior such as contact precautions and social distancing clearly influence disease prevalence, but disease prevalence can in turn alter human behavior, forming a coupled, nonlinear system. Moreover, in many cases, the spatial structure of the population cannot be ignored, such that social and behavioral processes and/or transmission of infection must be represented with complex networks. Research on studying coupled disease-behavior dynamics in complex networks in particular is growing rapidly, and frequently makes use of analysis methods and concepts from statistical physics. Here, we review some of the growing literature in this area. We contrast network-based approaches to homogeneous-mixing approaches, point out how their predictions differ, and describe the rich and often surprising behavior of disease-behavior dynamics on complex networks, and compare them to processes in statistical physics. We discuss how these models can capture the dynamics that characterize many real-world scenarios, thereby suggesting ways that policy makers can better design effective prevention strategies. We also describe the growing sources of digital data that are facilitating research in this area. Finally, we suggest pitfalls which might be faced by researchers in the field, and we suggest several ways in which the field could move forward in the coming years.