Prediction Models Discriminating between Nonlocomotive and Locomotive Activities in Children Using a Triaxial Accelerometer with a Gravity-removal Physical Activity Classification Algorithm

The aims of our study were to examine whether a gravity-removal physical activity classification algorithm (GRPACA) is applicable for discrimination between nonlocomotive and locomotive activities for various physical activities (PAs) of children and to prove that this approach improves the estimation accuracy of a prediction model for children using an accelerometer. Japanese children (42 boys and 26 girls) attending primary school were invited to participate in this study. We used a triaxial accelerometer with a sampling interval of 32 Hz and within a measurement range of ±6 G. Participants were asked to perform 6 nonlocomotive and 5 locomotive activities. We measured raw synthetic acceleration with the triaxial accelerometer and monitored oxygen consumption and carbon dioxide production during each activity with the Douglas bag method. In addition, the resting metabolic rate (RMR) was measured with the subject sitting on a chair to calculate metabolic equivalents (METs). When the ratio of unfiltered synthetic acceleration (USA) and filtered synthetic acceleration (FSA) was 1.12, the rate of correct discrimination between nonlocomotive and locomotive activities was excellent, at 99.1% on average. As a result, a strong linear relationship was found for both nonlocomotive (METs = 0.013×synthetic acceleration +1.220, R² = 0.772) and locomotive (METs = 0.005×synthetic acceleration +0.944, R² = 0.880) activities, except for climbing down and up. The mean differences between the values predicted by our model and measured METs were −0.50 to 0.23 for moderate to vigorous intensity (>3.5 METs) PAs like running, ball throwing and washing the floor, which were regarded as unpredictable PAs. In addition, the difference was within 0.25 METs for sedentary to mild moderate PAs (<3.5 METs). Our specific calibration model that discriminates between nonlocomotive and locomotive activities for children can be useful to evaluate the sedentary to vigorous PAs intensity of both nonlocomotive and locomotive activities.     

Plasma Zinc Concentration,Body Composition and Physical Activity in Obese Preschool Children

Zinc (Zn) deficiency and obesity can be observed together in some developing countries. Zn deficiency may enhance fat deposition and decrease lean mass accrual, which in turn, appears to influence physical activity (PA), although this has not yet been evaluated in obese children. The objective of the study was to find out the association between measurements of plasma Zn and serum leptin, body composition, and PA in Chilean obese preschool children. Seventy-two 18- to 36-month-old obese children [weight-for-length/height z score (WHZ) > 2.0 SD], belonging to low socioeconomic communities, participated in the study. Plasma Zn, serum leptin, weight, waist circumference, height, total body water (TBW) assessed by deuterium isotopic dilution technique and daily activity, measured by registering 48 h with an accelerometer, were evaluated. We found 82% of children with WHZ > 3 SD. The geometric mean Zn intake was 6.2 ± 2.5 mg/day. The mean plasma Zn was 91.8 ± 11.4 μg/dL, with 10% of the children having levels <80 μg/dL. No correlation was found between plasma Zn concentrations and either weight, WHZ, or waist circumference. Serum leptin was lower in males than in females (2.9 ± 2.8 vs 6.8 ± 5.0 ng/mL, respectively; p < 0.001). TBW was different between males and females (56.2 ± 5.4 vs 52.8 ± 4.3% body weight, respectively; p = 0.004), but no significant association was found between TBW and plasma Zn. Moderate + intense PA, (as percentage of wake time), was greater in males than in females (6.3 ± 3.1% vs 3.4 ± 2.3%, respectively; p < 0.001), but it was not significantly correlated to plasma Zn. In conclusion, plasma Zn was not associated with body composition as assessed by TBW, serum leptin, or with the magnitude of physical activity in Chilean overweight preschool children.     

Validation of a Fecal Glucocorticoid Assay to Assess Adrenocortical Activity in Meerkats Using Physiological and Biological Stimuli

In mammals, glucocorticoid (i.e. GC) levels have been associated with specific life-history stages and transitions, reproductive strategies, and a plethora of behaviors. Assessment of adrenocortical activity via measurement of glucocorticoid metabolites in feces (FGCM) has greatly facilitated data collection from wild animals, due to its non-invasive nature, and thus has become an established tool in behavioral ecology and conservation biology. The aim of our study was to validate a fecal glucocorticoid assay for assessing adrenocortical activity in meerkats (Suricata suricatta), by comparing the suitability of three GC enzyme immunoassays (corticosterone, 11β-hydroxyetiocholanolone and 11oxo-etiocholanolone) in detecting FGCM increases in adult males and females following a pharmacological challenge with adrenocorticotropic hormone (ACTH) and biological stimuli. In addition, we investigated the time course characterizing FGCM excretion, the effect of age, sex and time of day on FGCM levels and assessed the potential effects of soil contamination (sand) on FGCM patterns. Our results show that the group specific 11β-hydroxyetiocholanolone assay was most sensitive to FGCM alterations, detecting significant and most distinctive elevations in FGCM levels around 25 h after ACTH administration. We found no age and sex differences in basal FGCM or on peak response levels to ACTH, but a marked diurnal pattern, with FGCM levels being substantially higher in the morning than later during the day. Soil contamination did not significantly affect FGCM patterns. Our results emphasize the importance of conducting assay validations to characterize species-specific endocrine excretion patterns, a crucial step to all animal endocrinology studies using a non-invasive approach.     

The Obesogenic Quality of the Home Environment: Associations with Diet,Physical Activity,TV Viewing,and BMI in Preschool Children

Objectives

The home environment is thought to play a key role in early weight trajectories, although direct evidence is limited. There is general agreement that multiple factors exert small individual effects on weight-related outcomes, so use of composite measures could demonstrate stronger effects. This study therefore examined whether composite measures reflecting the ‘obesogenic’ home environment are associated with diet, physical activity, TV viewing, and BMI in preschool children.

Methods

Families from the Gemini cohort (n = 1096) completed a telephone interview (Home Environment Interview; HEI) when their children were 4 years old. Diet, physical activity, and TV viewing were reported at interview. Child height and weight measurements were taken by the parents (using standard scales and height charts) and reported at interview. Responses to the HEI were standardized and summed to create four composite scores representing the food (sum of 21 variables), activity (sum of 6 variables), media (sum of 5 variables), and overall (food composite/21 + activity composite/6 + media composite/5) home environments. These were categorized into ‘obesogenic risk’ tertiles.

Results

Children in ‘higher-risk’ food environments consumed less fruit (OR; 95% CI = 0.39; 0.27–0.57) and vegetables (0.47; 0.34–0.64), and more energy-dense snacks (3.48; 2.16–5.62) and sweetened drinks (3.49; 2.10–5.81) than children in ‘lower-risk’ food environments. Children in ‘higher-risk’ activity environments were less physically active (0.43; 0.32–0.59) than children in ‘lower-risk’ activity environments. Children in ‘higher-risk’ media environments watched more TV (3.51; 2.48–4.96) than children in ‘lower-risk’ media environments. Neither the individual nor the overall composite measures were associated with BMI.

Conclusions

Composite measures of the obesogenic home environment were associated as expected with diet, physical activity, and TV viewing. Associations with BMI were not apparent at this age.     

Variability in Physical Activity Assessed with Accelerometer Is an Independent Predictor of Mortality in CHF Patients

AimsPatients with heart failure often display a distinct pattern of walking characterized by short step-length and frequent short pauses. In the current study we sought to explore if qualitative aspects of movement have any additive value to established factors to predict all-cause mortality in patients with advanced heart failure.ConclusionThe feature skewness, a measure of asymmetry in the intensity level of periods of high physical activity, was identified to be predictive of all-cause mortality independent of the established prognostic model–HFSS and peak VO2. The findings from the present study emphasize the use of accelerometer analysis in clinical practice to make more accurate prognoses in addition to extract features of physical activity relevant to functional classification.     

Influence of Accelerometer Type and Placement on Physical Activity Energy Expenditure Prediction in Manual Wheelchair Users

PurposeTo assess the validity of two accelerometer devices, at two different anatomical locations, for the prediction of physical activity energy expenditure (PAEE) in manual wheelchair users (MWUs).MethodsSeventeen MWUs (36 ± 10 yrs, 72 ± 11 kg) completed ten activities; resting, folding clothes, propulsion on a 1% gradient (3,4,5,6 and 7 km·hr^-1) and propulsion at 4km·hr^-1 (with an additional 8% body mass, 2% and 3% gradient) on a motorised wheelchair treadmill. GT3X+ and GENEActiv accelerometers were worn on the right wrist (W) and upper arm (UA). Linear regression analysis was conducted between outputs from each accelerometer and criterion PAEE, measured using indirect calorimetry. Subsequent error statistics were calculated for the derived regression equations for all four device/location combinations, using a leave-one-out cross-validation analysis.ResultsAccelerometer outputs at each anatomical location were significantly (p < .01) associated with PAEE (GT3X+-UA; r = 0.68 and GT3X+-W; r = 0.82. GENEActiv-UA; r = 0.87 and GENEActiv-W; r = 0.88). Mean ± SD PAEE estimation errors for all activities combined were 15 ± 45%, 14 ± 50%, 3 ± 25% and 4 ± 26% for GT3X+-UA, GT3X+-W, GENEActiv-UA and GENEActiv-W, respectively. Absolute PAEE estimation errors for devices varied, 19 to 66% for GT3X+-UA, 17 to 122% for GT3X+-W, 15 to 26% for GENEActiv-UA and from 17.0 to 32% for the GENEActiv-W.ConclusionThe results indicate that the GENEActiv device worn on either the upper arm or wrist provides the most valid prediction of PAEE in MWUs. Variation in error statistics between the two devices is a result of inherent differences in internal components, on-board filtering processes and outputs of each device.     

The Cultural Validation of Two Scales to Assess Social Stigma in Leprosy

Background

Stigma plays in an important role in the lives of persons affected by neglected tropical diseases, and assessment of stigma is important to document this. The aim of this study is to test the cross-cultural validity of the Community Stigma Scale (EMIC-CSS) and the Social Distance Scale (SDS) in the field of leprosy in Cirebon District, Indonesia.

Methodology/principle findings

Cultural equivalence was tested by assessing the conceptual, item, semantic, operational and measurement equivalence of these instruments. A qualitative exploratory study was conducted to increase our understanding of the concept of stigma in Cirebon District. A process of translation, discussions, trainings and a pilot study followed. A sample of 259 community members was selected through convenience sampling and 67 repeated measures were obtained to assess the psychometric measurement properties. The aspects and items in the SDS and EMIC-CSS seem equally relevant and important in the target culture. The response scales were adapted to ensure that meaning is transferred accurately and no changes to the scale format (e.g. lay out, statements or questions) of both scales were made. A positive correlation was found between the EMIC-CSS and the SDS total scores (r = 0.41). Cronbach''s alphas of 0.83 and 0.87 were found for the EMIC-CSS and SDS. The exploratory factor analysis indicated for both scales an adequate fit as unidimensional scale. A standard error of measurement of 2.38 was found in the EMIC-CSS and of 1.78 in the SDS. The test-retest reliability coefficient was respectively, 0.84 and 0.75. No floor or ceiling effects were found.

Conclusions/significance

According to current international standards, our findings indicate that the EMIC-CSS and the SDS have adequate cultural validity to assess social stigma in leprosy in the Bahasa Indonesia-speaking population of Cirebon District. We believe the scales can be further improved, for instance, by adding, changing and rephrasing certain items. Finally, we provide suggestions for use with other neglected tropical diseases.     

A Novel,Open Access Method to Assess Sleep Duration Using a Wrist-Worn Accelerometer

Wrist-worn accelerometers are increasingly being used for the assessment of physical activity in population studies, but little is known about their value for sleep assessment. We developed a novel method of assessing sleep duration using data from 4,094 Whitehall II Study (United Kingdom, 2012–2013) participants aged 60–83 who wore the accelerometer for 9 consecutive days, filled in a sleep log and reported sleep duration via questionnaire. Our sleep detection algorithm defined (nocturnal) sleep as a period of sustained inactivity, itself detected as the absence of change in arm angle greater than 5 degrees for 5 minutes or more, during a period recorded as sleep by the participant in their sleep log. The resulting estimate of sleep duration had a moderate (but similar to previous findings) agreement with questionnaire based measures for time in bed, defined as the difference between sleep onset and waking time (kappa = 0.32, 95%CI:0.29,0.34) and total sleep duration (kappa = 0.39, 0.36,0.42). This estimate was lower for time in bed for women, depressed participants, those reporting more insomnia symptoms, and on weekend days. No such group differences were found for total sleep duration. Our algorithm was validated against data from a polysomnography study on 28 persons which found a longer time window and lower angle threshold to have better sensitivity to wakefulness, while the reverse was true for sensitivity to sleep. The novelty of our method is the use of a generic algorithm that will allow comparison between studies rather than a “count” based, device specific method.     

The Value of Body Weight Measurement to Assess Dehydration in Children

Dehydration secondary to gastroenteritis is one of the most common reasons for office visits and hospital admissions. The indicator most commonly used to estimate dehydration status is acute weight loss. Post-illness weight gain is considered as the gold-standard to determine the true level of dehydration and is widely used to estimate weight loss in research. To determine the value of post-illness weight gain as a gold standard for acute dehydration, we conducted a prospective cohort study in which 293 children, aged 1 month to 2 years, with acute diarrhea were followed for 7 days during a 3-year period. The main outcome measures were an accurate pre-illness weight (if available within 8 days before the diarrhea), post-illness weight, and theoretical weight (predicted from the child’s individual growth chart). Post-illness weight was measured for 231 (79%) and both theoretical and post-illness weights were obtained for 111 (39%). Only 62 (21%) had an accurate pre-illness weight. The correlation between post-illness and theoretical weight was excellent (0.978), but bootstrapped linear regression analysis showed that post-illness weight underestimated theoretical weight by 0.48 kg (95% CI: 0.06–0.79, p<0.02). The mean difference in the fluid deficit calculated was 4.0% of body weight (95% CI: 3.2–4.7, p<0.0001). Theoretical weight overestimated accurate pre-illness weight by 0.21 kg (95% CI: 0.08–0.34, p = 0.002). Post-illness weight underestimated pre-illness weight by 0.19 kg (95% CI: 0.03–0.36, p = 0.02). The prevalence of 5% dehydration according to post-illness weight (21%) was significantly lower than the prevalence estimated by either theoretical weight (60%) or clinical assessment (66%, p<0.0001).These data suggest that post-illness weight is of little value as a gold standard to determine the true level of dehydration. The performance of dehydration signs or scales determined by using post-illness weight as a gold standard has to be reconsidered.     

Biosensors to Assess the Activity of Promoters and Chaperones in Bacillus subtilis Cells

Applied Biochemistry and Microbiology - Plasmids have been constructed to determine the activities of promoters in Bacillus subtilis cells. The plasmids contain constitutive (PfbaA, PymdA_mut3,...     

Energy Expenditure Compared to Physical Activity Measured by Accelerometry and Self-Report in Adolescents: A Validation Study

Background

Physical inactivity is responsible for 5.3 million deaths annually worldwide. To measure physical activity energy expenditure, the doubly labeled water (DLW) method is the gold standard. However, questionnaires and accelerometry are more widely used. We compared physical activity measured by accelerometer and questionnaire against total (TEE) and physical activity energy expenditure (PAEE) estimated by DLW.

Methods

TEE, PAEE (TEE minus resting energy expenditure) and body composition were measured using the DLW technique in 25 adolescents (16 girls) aged 13 years living in Pelotas, Brazil. Physical activity was assessed using the Actigraph accelerometer and by self-report. Physical activity data from accelerometry and self-report were tested against energy expenditure data derived from the DLW method. Further, tests were done to assess the ability of moderate-to-vigorous intensity physical activity (MVPA) to predict variability in TEE and to what extent adjustment for fat and fat-free mass predicted the variability in TEE.

Results

TEE varied from 1,265 to 4,143 kcal/day. It was positively correlated with physical activity (counts) estimated by accelerometry (rho  = 0.57; p = 0.003) and with minutes per week of physical activity by questionnaire (rho  = 0.41; p = 0.04). An increase of 10 minutes per day in moderate-to-vigorous intensity physical activity (MVPA) relates to an increase in TEE of 141 kcal/day. PAEE was positively correlated with accelerometry (rho  = 0.64; p = 0.007), but not with minutes per week of physical activity estimated by questionnaire (rho  = 0.30; p = 0.15). Physical activity by accelerometry explained 31% of the vssariability in TEE. By incorporating fat and fat-free mass in the model, we were able to explain 58% of the variability in TEE.

Conclusion

Objectively measured physical activity significantly contributes to the explained variance in both TEE and PAEE in Brazilian youth. Independently, body composition also explains variance in TEE, and should ideally be taken into account when using accelerometry to predict energy expenditure values.     

A Permutation Method to Assess Heterogeneity in External Validation for Risk Prediction Models

The value of a developed prediction model depends on its performance outside the development sample. The key is therefore to externally validate the model on a different but related independent data. In this study, we propose a permutation method to assess heterogeneity in external validation for risk prediction models. The permutation p value measures the extent of homology between development and validation datasets. If p < 0.05, the model may not be directly transported to the external validation population without further revision or updating. Monte-Carlo simulations are conducted to evaluate the statistical properties of the proposed method, and two microarray breast cancer datasets are analyzed for demonstration. The permutation method is easy to implement and is recommended for routine use in external validation for risk prediction models.     

Examination of Different Accelerometer Cut-Points for Assessing Sedentary Behaviors in Children

Background

Public health research on sedentary behavior (SB) in youth has heavily relied on accelerometers. However, it has been limited by the lack of consensus on the most accurate accelerometer cut-points as well as by unknown effects caused by accelerometer position (wrist vs. hip) and output (single axis vs. multiple axes). The present study systematically evaluates classification accuracy of different Actigraph cut-points for classifying SB using hip and wrist-worn monitors and establishes new cut-points to enable use of the 3-dimensional vector magnitude data (for both hip and wrist placement).

Methods

A total of 125 children ages 7–13 yrs performed 12 randomly selected activities (from a set of 24 different activities) for 5 min each while wearing tri-axial Actigraph accelerometers on both the hip and wrist. The accelerometer data were categorized as either sedentary or non-sedentary minutes using six previously studied cut-points: 100counts-per-minute (CPM), 200CPM, 300CPM, 500CPM, 800CPM and 1100CPM. Classification accuracy was evaluated with Cohen''s Kappa (κ) and new cut-points were identified from Receiver Operating Characteristic (ROC).

Results

Of the six cut-points, the 100CPM value yielded the highest classification accuracy (κ = 0.81) for hip placement. For wrist placement, all of the cut-points produced low classification accuracy (ranges of κ from 0.44 to 0.67). Optimal sedentary cut-points derived from ROC were 554.3CPM (ROC-AUC of 0.99) for vector magnitude for hip, 1756CPM (ROC-AUC of 0.94) for vertical axis for wrist, and 3958.3CPM (ROC-AUC of 0.93) for vector magnitude for wrist placement.

Conclusions

The 100CPM was supported for use with vertical axis for hip placement, but not for wrist placement. The ROC-derived cut-points can be used to classify youth SB with the wrist and with vector magnitude data.     

Localization of Physical Activity in Primary School Children Using Accelerometry and Global Positioning System

Background

Ecological approaches have highlighted the importance of the built environment as a factor affecting physical activity. However, knowledge on children’s activity patterns is still incomplete. Particularly, data on the spatial context of physical activity is limited, which limits the potential to design location-based interventions effectively. Using global positioning system (GPS) and accelerometry, this study aimed to identify locations where children engage in moderate-vigorous physical activity (MVPA).

Methods

Participants included 119 children (11–14 years, 57% girls) from public schools in Winterthur, Switzerland. During a regular school week between February and April 2013, children wore an accelerometer and GPS sensor for seven consecutive days. Time-matched accelerometer and GPS data was mapped with a geographic information system and each data point was assigned to one of seven defined activity settings. Both the absolute amount of MVPA and proportion of time in MVPA were calculated for every setting. Multilevel analyses accounting for the hierarchical structure of the data were conducted to investigate any gender differences.

Results

Children achieved most MVPA on streets (34.5%) and on school grounds (33.4%). The proportion children spent in MVPA was highest in recreational facilities (19.4%), at other schools (19.2%) and on streets (18.6%). Boys accumulated significantly more MVPA overall and on other school grounds (p < 0.05) and showed a significantly higher proportion of time in MVPA at own school and outside of Winterthur (p < 0.05).

Conclusions

The results indicate the importance of streets and school grounds as activity-promoting environments. The high use of streets may be an indicator for active transportation, which appears to contribute to an active lifestyle in both genders. In contrast, the school setting is more likely to encourage physical activity in boys. Recreational facilities seem to be conducive for MVPA among both genders, although infrequently visited during the week of measurement.     

Heart Rate and Stroke Volume Responses in Children of Early School Age to Change in Their Physical Activity Regimen

A study was made of the adaptation of the cardiac pump function in children of early school age to change in their physical activity associated with the transition from preschool to elementary school. Children of the experimental group, who engaged in physical exercise daily over the first school year, developed so-called bradycardia of training, which enhanced the tendency of the heart rate to decrease with age. The level of bradycardia attained in the first school year was retained over the two subsequent years, despite a considerable decrease in the amount of physical activity in this period. Daily exercising significantly increased the stroke volume, which remained at a high level even after the daily exercising program was stopped. Children of the control group participated only in physical activities of the regular physical education program. Their heart rate remained unchanged over the first two school years. At the beginning of the third year, a decrease in the heart rate and a rise in the stroke volume were observed, as expected of their age.     

Development of the Intrinsic Language Network in Preschool Children from Ages 3 to 5 Years

Resting state studies of spontaneous fluctuations in the functional magnetic resonance imaging (fMRI) blood oxygen level dependent signal have shown great potential in mapping the intrinsic functional connectivity of the human brain underlying cognitive functions. The aim of the present study was to explore the developmental changes in functional networks of the developing human brain exemplified with the language network in typically developing preschool children. To this end, resting-sate fMRI data were obtained from native Chinese children at ages of 3 and 5 years, 15 in each age group. Resting-state functional connectivity (RSFC) was analyzed for four regions of interest; these are the left and right anterior superior temporal gyrus (aSTG), left posterior superior temporal gyrus (pSTG), and left inferior frontal gyrus (IFG). The comparison of these RSFC maps between 3- and 5-year-olds revealed that RSFC decreases in the right aSTG and increases in the left hemisphere between aSTG seed and IFG, between pSTG seed and IFG, as well as between IFG seed and posterior superior temporal sulcus. In a subsequent analysis, functional asymmetry of the language network seeding in aSTG, pSTG and IFG was further investigated. The results showed an increase of left lateralization in both RSFC of pSTG and of IFG from ages 3 to 5 years. The IFG showed a leftward lateralized trend in 3-year-olds, while pSTG demonstrated rightward asymmetry in 5-year-olds. These findings suggest clear developmental trajectories of the language network between 3- and 5-year-olds revealed as a function of age, characterized by increasing long-range connections and dynamic hemispheric lateralization with age. Our study provides new insights into the developmental changes of a well-established functional network in young children and also offers a basis for future cross-culture and cross-age studies of the resting-state language network.     

Effects of Varying Epoch Lengths,Wear Time Algorithms,and Activity Cut-Points on Estimates of Child Sedentary Behavior and Physical Activity from Accelerometer Data

Objective

To examine the effects of accelerometer epoch lengths, wear time (WT) algorithms, and activity cut-points on estimates of WT, sedentary behavior (SB), and physical activity (PA).

Methods

268 7–11 year-olds with BMI ≥ 85^th percentile for age and sex wore accelerometers on their right hips for 4–7 days. Data were processed and analyzed at epoch lengths of 1-, 5-, 10-, 15-, 30-, and 60-seconds. For each epoch length, WT minutes/day was determined using three common WT algorithms, and minutes/day and percent time spent in SB, light (LPA), moderate (MPA), and vigorous (VPA) PA were determined using five common activity cut-points. ANOVA tested differences in WT, SB, LPA, MPA, VPA, and MVPA when using the different epoch lengths, WT algorithms, and activity cut-points.

Results

WT minutes/day varied significantly by epoch length when using the NHANES WT algorithm (p < .0001), but did not vary significantly by epoch length when using the ≥ 20 minute consecutive zero or Choi WT algorithms. Minutes/day and percent time spent in SB, LPA, MPA, VPA, and MVPA varied significantly by epoch length for all sets of activity cut-points tested with all three WT algorithms (all p < .0001). Across all epoch lengths, minutes/day and percent time spent in SB, LPA, MPA, VPA, and MVPA also varied significantly across all sets of activity cut-points with all three WT algorithms (all p < .0001).

Conclusions

The common practice of converting WT algorithms and activity cut-point definitions to match different epoch lengths may introduce significant errors. Estimates of SB and PA from studies that process and analyze data using different epoch lengths, WT algorithms, and/or activity cut-points are not comparable, potentially leading to very different results, interpretations, and conclusions, misleading research and public policy.