Overestimation of stereo thresholds by the TNO stereotest is not due to global stereopsis.

PURPOSE: It has been repeatedly shown that the TNO stereotest overestimates stereo threshold compared to other clinical stereotests. In the current study, we test whether this overestimation can be attributed to a distinction between 'global' (or 'cyclopean') and 'local' (feature or contour-based) stereopsis. METHODS: We compared stereo thresholds of a global (TNO) and a local clinical stereotest (Randot Circles). In addition, a global and a local psychophysical stereotest were added to the design. One hundred and forty-nine children between 4 and 16 years old were included in the study. RESULTS: Stereo threshold estimates with TNO were a factor of two higher than with any of the other stereotests. No significant differences were found between the other tests. Bland-Altman analyses also indicated low agreement between TNO and the other stereotests, especially for higher stereo threshold estimates. Simulations indicated that the TNO test protocol and test disparities can account for part of this effect. DISCUSSION: The results indicate that the global - local distinction is an unlikely explanation for the overestimated thresholds of TNO. Test protocol and disparities are one contributing factor. Potential additional factors include the nature of the task (TNO requires depth discrimination rather than detection) and the use of anaglyph red/green 3D glasses rather than polarizing filters, which may reduce binocular fusion.

Clinical Perineal Streptococcal Infection in Children: Epidemiologic Features, Low Symptomatic Recurrence Rate after Treatment, and Risk Factors for Recurrence.

OBJECTIVES: To evaluate the epidemiology of perineal streptococcal infection and recurrence rates following amoxicillin treatment. STUDY DESIGN: We used laboratory logs in a single pediatric practice to identify patients 0-18 years of age with perineal cultures positive for group A Streptococcus (GAS) and reviewed their medical charts. We described epidemiologic features, determined recurrence rates following antibiotic treatment, and performed a case-control study to identify possible risk factors for recurrence in patients treated with amoxicillin. RESULTS: We found a perineal streptococcal infection rate of 4.6 per 10,000 patient encounters and a recurrence rate in 157 patients with perineal streptococcal infection of 12.4% after amoxicillin. In male patients, the predominant site of involvement was the perianal region (86%), and for female patients, the perivaginal area (62%). Nearly 80% of patients were 2-7 years of age (range 18 days-12.5 years). Perineal streptococcal infection and GAS pharyngitis followed a similar seasonal pattern of occurrence with 65% of perineal streptococcal infection occurring October through March. In patients with perineal streptococcal infection, 95% had a concomitant pharyngeal culture positive for GAS. Best predictive factors for recurrence after amoxicillin were longer duration of symptoms prior to diagnosis and having a sibling with perineal streptococcal infection at some time before or after the initial episode. CONCLUSIONS: Following treatment with amoxicillin, we found a low recurrence rate of 12.4%. Amoxicillin can be expected to be reliable first-line therapy for perineal streptococcal infection.

The contrast sensitivity function of the praying mantis Sphodromantis lineola.

The detection of visual motion and its direction is a fundamental task faced by several visual systems. The motion detection system of insects has been widely studied with the majority of studies focussing on flies and bees. Here we characterize the contrast sensitivity of motion detection in the praying mantis Sphodromantis lineola, an ambush predator that stays stationary for long periods of time while preying on fast-moving prey. In this, its visual behaviour differs from previously studied insects and we might therefore expect its motion detection system to differ from theirs. To investigate the sensitivity of the mantis we analyzed its optomotor response in response to drifting gratings with different contrasts and spatio-temporal frequencies. We find that the contrast sensitivity of the mantis depends on the spatial and temporal frequencies present in the stimulus and is separably tuned to spatial and temporal frequency rather than specifically to object velocity. Our results also suggest that mantises are sensitive to a broad range of velocities, in which they differ from bees and are more similar to hoverflies. We discuss our results in relation to the contrast sensitivities of other insects and the visual ecology of the mantis.

Relationship of obstructive sleep apnea and cardiometabolic risk factors in elderly patients with abdominal aortic aneurysm.

PURPOSE: This study seeks to determine the risks for obstructive sleep apnea (OSA) and cardiometabolic disease (CMR) in elderly patients with mild-moderate abdominal aortic aneurysms (AAA). METHODS: Three hundred two elderly patients with diagnosed small AAA disease were subjects. CMR was assessed by several biomarkers, with special focus on the Lipid Accumulation Product (LAP) and the Triglyceride-Glucose Index (TyG Index), two validated screening indicators of CMR related to central obesity and insulin resistance, respectively. Analysis of OSA risk was assessed with the Berlin Questionnaire. RESULTS: The patients (60.6 %) had increased risk of OSA; those at high risk also were at increased (p < 0.05) risk for CMR (15/25 biomarkers). CONCLUSIONS: As a group, elderly AAA patients are at risk for both OSA and cardiometabolic disease. Given that OSA and CMR may both amplify risk for AAA expansion, these patients should be screened for OSA, and when indicated, referred for definitive evaluation and treatment.

Comparison of patient attitudes and provider perceptions regarding medical student involvement in obstetric/gynecologic care.

BACKGROUND: Community physicians are becoming increasingly involved in clinical medical education. Some obstetrician/gynecologists have expressed reluctance to participate as clinical preceptors for medical students due to the sensitive nature of many of their patient encounters and concern for diminished patient satisfaction. PURPOSES: The purpose was to evaluate the willingness of community ob/gyn patients to participate in clinical medical education and to determine the accuracy of provider perceptions regarding this issue. METHODS: Surveys were distributed to women seeking ob/gyn care at 4 private practice sites in Tucson, Arizona. The surveys explored patient attitudes toward community physician involvement in clinical medical education as well as factors influencing personal willingness to include students as part of their healthcare team. Similar surveys were administered to the ob/gyn providers in those sites and evaluated their expectations of aggregate patient responses. RESULTS: Of 234 patient respondents, 87.6% believed that physicians have a responsibility to participate in medical education. Providers underestimated the number of patients for whom such participation would positively influence their personal provider choice (12.7% vs. 30.8%, p<.01) and overestimated negative (16.7% vs. 6.8%, p<.01) influence. Providers also underestimated acceptance rates of student pelvic examinations based on learner gender (13.8% vs. 24.3% male students, p=.01; 28.1% vs. 44.4% female students, p<.01). CONCLUSIONS: Patients in southern Arizona recognize and appreciate physicians' responsibility to educate future providers of women's healthcare. Providers may underestimate patient acceptance and value of students as part of their healthcare team. This bias may unnecessarily limit student exposure to clinical learning opportunities.

Disparities in adherence to physical activity guidelines among US adults: A population-based study.

The objective of this study was to determine adherence to national guidelines for aerobic and muscle-strengthening physical activity among United States (US) adults and identify factors associated with guideline nonadherence. The 2022 National Health Interview Survey data were analyzed to evaluate self-reported physical activity among 26,494 US adults. Adherence to national guidelines was defined as engaging in ≥150 minutes moderate-intensity or ≥75 minutes vigorous-intensity aerobic activity/week, and muscle-strengthening activity ≥2 days/week. A multivariable logistic regression model evaluated associations between 24 sociodemographic and health variables with nonadherence to physical activity guidelines. Shapley Additive Explanations were used to assess the relative importance of each factor in the model. The population-weighted analysis revealed that only 24.3% of US adults met both the aerobic and muscle-strengthening activity guidelines. The regression model identified 17 factors significantly associated with nonadherence. When evaluating the relative importance of these variables, older age, lower educational attainment, and lower household income emerged as the primary determinants of nonadherence. Guideline adherence was lowest among subgroups with multiple risk factors, with only 6.5% of older adults with lower income and education meeting the guidelines. In contrast, adherence was 42.7% in younger respondents with higher incomes and educational attainment. In conclusion, physical activity rates among US adults remain below public health targets, with significant disparities among sociodemographic groups. Expanded outreach efforts targeting higher-risk populations are urgently needed to address barriers, promote physical activity engagement, and achieve health equity.

Oxidative stress, redox status and surfactant metabolism in mechanically ventilated patients receiving different approaches to oxygen therapy (MecROX): An observational study protocol for mechanistic evaluation.

Background: MecROX is a mechanistic sub-study of the UK-ROX trial which was designed to evaluate the clinical and cost-effectiveness of a conservative approach to oxygen therapy for invasively ventilated adults in intensive care. This is based on the scientific rationale that excess oxygen is harmful. Epithelial cell damage with alveolar surfactant deficiency is characteristic of hyperoxic acute lung injury. Additionally, hyperoxaemia (excess blood oxygen levels) may exacerbate whole-body oxidative stress leading to cell death, autophagy, mitochondrial dysfunction, bioenergetic failure and multi-organ failure resulting in poor clinical outcomes. However, there is a lack of in-vivo human models evaluating the mechanisms that underpin oxygen-induced organ damage in mechanically ventilated patients. Aim: The aim of the MecROX mechanistic sub-study is to assess lung surfactant composition and global systemic redox status to provide a mechanistic and complementary scientific rationale to the UK-ROX trial findings. The objectives are to quantify in-vivo surfactant composition, synthesis, and metabolism with markers of oxidative stress and systemic redox disequilibrium (as evidenced by alterations in the 'reactive species interactome') to differentiate between groups of conservative and usual oxygen targets. Methods and design: After randomisation into the UK-ROX trial, 100 adult participants (50 in the conservative and 50 in usual care group) will be recruited at two trial sites. Blood and endotracheal samples will be taken at 0, 48 and 72 hours following an infusion of 3 mg/kg methyl-D 9-choline chloride. This is a non-radioactive, stable isotope of choline (vitamin), which has been extensively used to study surfactant phospholipid kinetics in humans. This study will mechanistically evaluate the in-vivo surfactant synthesis and breakdown (by hydrolysis and oxidation), oxidative stress and redox disequilibrium from sequential plasma and bronchial samples using an array of analytical platforms. We will compare conservative and usual oxygenation groups according to the amount of oxygen administered. Trial registration: ISRCTNISRCTN61929838, 27/03/2023 https://doi.org/10.1186/ISRCTN61929838.

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.

Fat and muscle indices assessed by pQCT: relationships with physical activity and type 2 diabetes risk.

The aim of this study was to compare and determine the repeatability of foreleg and forearm muscle and fat indices evaluated by the peripheral quantitative computed tomography (pQCT). Effects of habitual physical activity and associated health risk of type 2 diabetes were examined within the interrelations of intermuscular adipose tissue (IMAT) and muscle density. Eighty-two premenopausal women (mean age ± standard deviation: 38.6 ± 4.7 yr) underwent dual-energy X-ray absorptiometry scans and pQCT of foreleg and forearm scans to assess muscle and fat parameters. Physical activity status was based on 4-d self-reported log and pedometer step counts. Fat and muscle distribution between the foreleg and forearm were similar and highly correlated to total body adiposity. The pQCT device reliably measured muscle density in the foreleg and forearm; coefficients of variation were 0.8% and 2.1%, which was therefore used to reflect IMAT status. Muscle density was positively related to physical activity and negatively associated with markers of fat distribution and risk for type 2 diabetes. The pQCT is a novel, noninvasive tool to assess IMAT and muscle density in the foreleg and forearm. Additional research is necessary to understand the biology of IMAT and its relations with physical activity and potentially, with risks for cardiometabolic disease.

Whole genome sequencing of cyanobacterium Nostoc sp. CCCryo 231-06 using microfluidic single cell technology.

The Nostoc sp. strain CCCryo 231-06 is a cyanobacterial strain capable of surviving under extreme conditions and thus is of great interest for the astrobiology community. The knowledge of its complete genome sequence would serve as a guide for further studies. However, a major concern has been placed on the effects of contamination on the quality of sequencing data without a reference genome. Here, we report the use of microfluidic technology combined with single cell sequencing and de novo assembly to minimize the contamination and recover the complete genome of the Nostoc strain CCCryo 231-06 with high quality. 100% of the whole genome was recovered with all contaminants removed and a strongly supported phylogenetic tree. The data reported can be useful for comparative genomics for phylogenetic and taxonomic studies. The method used in this work can be applied to studies that require high-quality assemblies of genomes of unknown microorganisms.

Non-random genetic alterations in the cyanobacterium Nostoc sp. exposed to space conditions.

Understanding the impact of long-term exposure of microorganisms to space is critical in understanding how these exposures impact the evolution and adaptation of microbial life under space conditions. In this work we subjected Nostoc sp. CCCryo 231-06, a cyanobacterium capable of living under many different ecological conditions, and also surviving in extreme ones, to a 23-month stay at the International Space Station (the Biology and Mars Experiment, BIOMEX, on the EXPOSE-R2 platform) and returned it to Earth for single-cell genome analysis. We used microfluidic technology and single cell sequencing to identify the changes that occurred in the whole genome of single Nostoc cells. The variant profile showed that biofilm and photosystem associated loci were the most altered, with an increased variant rate of synonymous base pair substitutions. The cause(s) of these non-random alterations and their implications to the evolutionary potential of single bacterial cells under long-term cosmic exposure warrants further investigation.

Porphyromonas somerae Invasion of Endometrial Cancer Cells.

Recent evidence suggests an association between endometrial cancer and the understudied bacterial species Porphyromonas somerae. This association was demonstrated in previous work that indicated a significantly enriched abundance of P. somerae in the uterine microbiome of endometrial cancer patients. Given the known associations of the Porphyromonas genus and oral cancer, we hypothesized that P. somerae may play a similar pathogenic role in endometrial cancer via intracellular activity. Before testing our hypothesis, we first characterized P. somerae biology, as current background data is limited. These novel characterizations include growth curves in liquid medium and susceptibility tests to antibiotics. We tested our hypothesis by examining growth changes in response to 17ß-estradiol, a known risk factor for endometrial cancer, followed by metabolomic profiling in the presence and absence of 17ß-estradiol. We found that P. somerae exhibits increased growth in the presence of 17ß-estradiol of various concentrations. However, we did not find significant changes in metabolite levels in response to 17ß-estradiol. To study direct host-microbe interactions, we used in vitro invasion assays under hypoxic conditions and found evidence for intracellular invasion of P. somerae in endometrial adenocarcinoma cells. We also examined these interactions in the presence of 17ß-estradiol but did not observe changes in invasion frequency. Invasion was shown using three lines of evidence including visualization via differential staining and brightfield microscopy, increased frequency of bacterial recovery after co-culturing, and in silico methods to detail relevant genomic and transcriptomic components. These results underscore potential intracellular phenotypes of P. somerae within the uterine microbiome. Furthermore, these results raise new questions pertaining to the role of P. somerae in the progression of endometrial cancer.

Gut and vaginal microbiomes on steroids: implications for women's health.

This review discusses the interactions of steroids with the gut and vaginal microbiomes within each life phase of adult women and the implications for women's health. Each phase of a woman's life is characterized by distinct hormonal states which drive overall physiology of both host and commensal microbes. These host-microbiome interactions underlie disease pathology in disorders that affect women across their lifetime, including bacterial vaginosis, gestational diabetes, polycystic ovary syndrome (PCOS), anxiety, depression, and obesity. Although many associations between host health and microbiome composition are well defined, the mechanistic role of the microbiome in women's health outcomes is largely unknown. This review addresses potential mechanisms by which the microbiota influences women's health and highlights gaps in current knowledge.

Efficient estimation of stereo thresholds: What slope should be assumed for the psychometric function?

Bayesian staircases are widely used in psychophysics to estimate detection thresholds. Simulations have revealed the importance of the parameters selected for the assumed subject's psychometric function in enabling thresholds to be estimated with small bias and high precision. One important parameter is the slope of the psychometric function, or equivalently its spread. This is often held fixed, rather than estimated for individual subjects, because much larger numbers of trials are required to estimate the spread as well as the threshold. However, if this fixed value is wrong, the threshold estimate can be biased. Here we determine the optimal slope to minimize bias and maximize precision when measuring stereoacuity with Bayesian staircases. We performed 2- and 4AFC disparity detection stereo experiments in order to measure the spread of the disparity psychometric function in human observers assuming a Logistic function. We found a wide range, between 0.03 and 3.5 log10 arcsec, with little change with age. We then ran simulations to examine the optimal spread using the empirical data. From our simulations and for three different experiments, we recommend selecting assumed spread values between the percentiles 60-80% of the population distribution of spreads (these percentiles can be extended to other type of thresholds). For stereo thresholds, we recommend a spread around the value σ = 1.7 log10 arcsec for 2AFC (slope ß = 4.3 /log10 arcsec), and around σ = 1.5 log10 arcsec for 4AFC (ß = 4.9 /log10 arcsec). Finally, we compared a Bayesian procedure (ZEST using the optimal σ) with five Bayesian procedures that are versions of ZEST-2D, Psi, and Psi-marginal. In general, for the conditions tested, ZEST optimal σ showed the lowest threshold bias and highest precision.

Isokinetic resistance training increases tibial bending stiffness in young women.

Bone mineral content (BMC) and bone mineral density (BMD) are common but imperfect surrogate measures of bone strength. The mechanical response tissue analyzer is a device that measures long bone bending stiffness (EI), which strongly predicts bone breaking strength. We hypothesized that isokinetic resistance training of the knee flexor and extensor muscles would increase tibial EI, BMC, and BMD in young women. Fifty-two women, aged 18-26 years, performed concentric (CON, n = 30) or eccentric (ECC, n = 22) isokinetic resistance training with the nondominant leg three times per week for 20 weeks. Before and after the training period, subjects were tested for CON and ECC peak torque of the knee flexor and extensor muscles with isokinetic dynamometry, tibial BMC and BMD using dual-energy X-ray absorptiometry, and tibial EI using mechanical response tissue analysis. Both training groups increased CON (15-21%) and ECC (17-31%) peak torque vs. the untrained leg. Tibial EI increased in the entire cohort (26%) and in each training group (CON 34%, ECC 16%) vs. the untrained tibia. Tibial BMC and BMD increased in the trained and untrained tibiae, with no significant differences between limbs. No differential tibial EI or bone mineral outcomes were observed between the CON and ECC training groups. In summary, CON and ECC isokinetic resistance training increased tibial EI, but not BMC or BMD, in young women.

Age influences anthropometric and fitness-related predictors of bone mineral in men.

OBJECTIVE: This study assessed the influence of age on the predictors of bone mineral in men. METHODS: Middle-age (n = 41, 54 +/- 4 yrs) and older (n = 40, 69 +/- 5 yrs) men underwent grip and knee extensor strength tests, total body dual-energy X-ray absorptiometry with regional analyses and a graded exercise treadmill test. RESULTS: Bone-free lean mass (BFLM) and, to a lesser extent, fat mass (FM) were correlated with bone mineral variables in middle-age men. In older men, BFLM and, to a lesser extent, FM were related to bone mineral content (BMC) at most sites, but inconsistently to bone mineral density (BMD). Knee extensor strength related to bone mineral (BMC and BMD) at most sites in middle-age men, but none in older men. Grip strength inconsistently related to bone mineral in both groups. Aerobic capacity related to bone mineral in middle-age men, but none in older men. In multiple regression, body weight or BFLM predicted bone mineral in middle-age men (R2 = 0.33-0.68) and BMC in older men (R2 = 0.33-0.50). Predictors of BMD were inconsistent in older men. CONCLUSIONS: Relationships of body composition, muscular strength and aerobic capacity to bone mineral are stronger in middle-age versus older men.

Attenuated heart rate recovery following exercise testing in overweight young men with untreated obstructive sleep apnea.

STUDY OBJECTIVE: To evaluate whether cardiovascular responses to maximal exercise testing and recovery are altered with obstructive sleep apnea (OSA) in overweight young adult men. DESIGN: Three sedentary subject groups were recruited: Overweight with OSA (OSA), overweight without OSA (No-OSA), and normal weight without OSA (Control). Presence of OSA was screened via portable diagnostic device. Body composition was measured with dual-energy X-ray absorptiometry. Subjects performed maximal ramping exercise testing (RXT) on a cycle ergometer with 5 minutes of active recovery. Exercise measurements included heart rate (HR), blood pressure (BP), respiratory exchange ratio (RER), and oxygen consumption (VO2). Recovery HR was converted to a HR difference (HR(diff)) calculation (HR(peak) - HR(each minute recovery)), and BP was converted to a recovery ratio for each minute. SETTING: The study was carried out on the campus of Virginia Tech, Department of Human Nutrition, Foods, and Exercise, Blacksburg, Virginia. PARTICIPANTS: 14 OSA, 16 No-OSA, and 14 Control volunteers. INTERVENTION: N/A. MEASUREMENTS AND RESULTS: In OSA subjects, HR recovery was significantly attenuated compared to the No-OSA and Control groups throughout recovery (P = 0.009). No differences were noted in the HR or BP response to exercise in any group. The VO2, adjusted for fat-free soft tissue mass, did not differ between groups. CONCLUSIONS: We found that OSA elicits alterations in the cardiovascular response post exercise, reflected by an attenuated HR recovery. This may indicate an imbalance in the autonomic regulation of HR. Exercise tests may provide utility in risk stratification for those at risk for OSA.

Small changes in nutrition and physical activity promote weight loss and maintenance: 3-month evidence from the ASPIRE randomized trial.

BACKGROUND: Current obesity interventions use intensive behavior changes to achieve large initial weight loss. However, weight regain after treatment is common, and drop out rates are relatively high. Smaller behavioral changes could produce initial weight loss and be easier to sustain after active treatment. PURPOSE: We examined the efficacy of an intervention that targeted small but cumulative participant-chosen changes in diet and physical activity (ASPIRE) and compared this treatment to standard didactic and wait-list control groups. The primary outcome measures were body weight, waist circumference, and intra-abdominal fat. METHODS: Fifty-nine overweight or obese sedentary adults were randomized to one of three groups: (1) the ASPIRE group (n = 20), (2) a standard educationally-based treatment group (n = 20), or (3) a wait list control group (n = 19) for 4 months. Active treatment groups received identical resistance and aerobic training programs. RESULTS: Intention-to-treat analyses showed that participants in the ASPIRE group lost significantly more weight than the standard and control groups (-4.4 vs. -1.1 and +0.1 kg, respectively), and the greater initial weight loss in the ASPIRE group was sustained 3 months after active treatment (4.1 kg). An alternative analytic strategy (0.3 kg/month weight gain for those lost to follow-up) showed continued weight loss (-0.2 kg after active treatment; -4.6 kg from baseline) at follow-up in the ASPIRE group. Similar patterns were observed for the other adiposity measures. CONCLUSION: More modest behavioral changes are capable of promoting weight loss, decreasing adiposity markers and sustaining these changes over 3 months. Longer-term studies comparing this approach with traditional behavioral weight loss treatments are warranted.

Is new science driving practice improvements and better patient outcomes? Applications for cardiac rehabilitation.

Evidence from many clinical trials in recent years suggests that a large "treatment gap" exists between recommended therapies and the care that patients actually receive. This gap has been particularly apparent in the area of primary and secondary prevention of cardiovascular disease. In this article, three areas are discussed in which new scientific advances have not been adequately translated to clinical practice. These include: 1) the most appropriate measures to define the risks associated with obesity; 2) the under-diagnosis of obstructive sleep apnea and its relation to cardiovascular risk; and 3) the use and misuse of the exercise test and other functional status tools to predict health outcomes. Each is discussed in terms of how they should be quantified, their contribution to the estimation of cardiovascular disease risk, their response to interventions, and implications for cardiac rehabilitation. Clinical cardiac rehabilitation programs can benefit from routinely including these measures, both for their value in stratifying risk and for their importance in quantifying program efficacy. Physicians and allied health professionals should expand their routine medical evaluations and coronary risk factor profiling to include these measures.