Personal best time and training volume, not anthropometry, is related to race performance in the 'Swiss Bike Masters' mountain bike ultramarathon

We investigated in 73 male ultraendurance mountain bikers, with (mean and SD) age 39.1 (8.6) years, weight 74.4 (8.3) kg, height 1.78 (0.07) m, and a body mass index of 23.3 (1.9) kg·m?2, whether variables of anthropometry, training, or prerace experience were associated with race time using bi and multivariate analysis. Our investigation was conducted at the "Swiss Bike Masters," which covers a distance of 120 km and an altitude of 5,000 m. In the bivariate analysis, body mass index (r = 0.29), circumference of upper arm (r = 0.28), sum of upper body skinfolds (r = 0.38), sum of lower body skinfolds (r = 0.25), sum of 8 skinfolds (r = 0.36), percent body fat (r = 0.41), total cycling kilometers per year (r = -0.47), yearly volume in both mountain bike (r = -0.33) and road cycling (r = -0.52), number of training units per week (r = -0.48), distance per unit in road cycling (r = -0.33), average speed during training in road cycling (r = -0.33), and personal best time in the "Swiss Bike Masters"(r = 0.67) were related to race time. In the multiple linear regression analysis, personal best time in the "Swiss Bike Masters" (p = 0.000), total yearly cycling kilometers (p = 0.004), and yearly training kilometers in road cycling (p = 0.017) were related to race time. When the personal best time was the dependent variable in a separate regression model, total yearly cycling kilometers (p = 0.002) remained the single predictor variable. We concluded that finishing a particular mountain bike ultramarathon does not seem to require a special anthropometry but rather a specific skill and experience for this selective kind of race coupled with a high training volume. For practical use, we concluded that successful athletes in a mountain bike ultramarathon, in a special environment and using sophisticated equipment, need prerace experience coupled with high training volume, rather than any special anthropometry.     

"Personal best times in an olympic distance triathlon and a marathon predict an ironman race time for recreational female triathletes"

"The aim of this study was to investigate whether the characteristics of anthropometry, training or previous performance were related to an Ironman race time in recreational female Ironman triathletes. These characteristics were correlated to an Ironman race time for 53 recreational female triathletes in order to determine the predictor variables, and so be able to predict an Ironman race time for future novice triathletes. In the bi-variate analysis, no anthropometric characteristic was related to race time. The weekly cycling kilometers (r = -0.35) and hours (r = -0.32), as well as the personal best time in an Olympic distance triathlon (r = 0.49) and in a marathon (r = 0.74) were related to an Ironman race time (< 0.05). Stepwise multiple regressions showed that both the personal best time in an Olympic distance triathlon ( P = 0.0453) and in a marathon (P = 0.0030) were the best predictors for the Ironman race time (n = 28, r2 = 0.53). The race time in an Ironman triathlon might be partially predicted by the following equation (r2 = 0.53, n = 28): Race time (min) = 186.3 + 1.595 × (personal best time in an Olympic distance triathlon, min) + 1.318 × (personal best time in a marathon, min) for recreational female Ironman triathletes."     

Effects of a concurrent strength and endurance training on running performance and running economy in recreational marathon runners

The purpose of this study was to investigate the effects of a concurrent strength and endurance training program on running performance and running economy of middle-aged runners during their marathon preparation. Twenty-two (8 women and 14 men) recreational runners (mean ± SD: age 40.0 ± 11.7 years; body mass index 22.6 ± 2.1 kg·m?2) were separated into 2 groups (n = 11; combined endurance running and strength training program [ES]: 9 men, 2 women and endurance running [E]: 7 men, and 4 women). Both completed an 8-week intervention period that consisted of either endurance training (E: 276 ± 108 minute running per week) or a combined endurance and strength training program (ES: 240 ± 121-minute running plus 2 strength training sessions per week [120 minutes]). Strength training was focused on trunk (strength endurance program) and leg muscles (high-intensity program). Before and after the intervention, subjects completed an incremental treadmill run and maximal isometric strength tests. The initial values for VO2peak (ES: 52.0 ± 6.1 vs. E: 51.1 ± 7.5 ml·kg?1·min?1) and anaerobic threshold (ES: 3.5 ± 0.4 vs. E: 3.4 ± 0.5 m·s?1) were identical in both groups. A significant time × intervention effect was found for maximal isometric force of knee extension (ES: from 4.6 ± 1.4 to 6.2 ± 1.0 N·kg?1, p < 0.01), whereas no changes in body mass occurred. No significant differences between the groups and no significant interaction (time × intervention) were found for VO2 (absolute and relative to VO2peak) at defined marathon running velocities (2.4 and 2.8 m·s?1) and submaximal blood lactate thresholds (2.0, 3.0, and 4.0 mmol·L?1). Stride length and stride frequency also remained unchanged. The results suggest no benefits of an 8-week concurrent strength training for running economy and coordination of recreational marathon runners despite a clear improvement in leg strength, maybe because of an insufficient sample size or a short intervention period.     

Effects of hip flexor training on sprint, shuttle run, and vertical jump performance

Although hip flexion is integral in sports, hip flexion exercises are seldom emphasized in strength and conditioning for sports performance. This study aimed to determine whether a hip flexor resistance-training program could improve performance on a variety of tasks. Thirteen men and 11 women completed an 8-week hip flexion resistance-training program. Eleven men and 13 women served as controls. Isometric hip flexion strength, 40-yd dash time and the time for the first 10-yds, 4 x 5.8-m shuttle run time, and vertical jump height were evaluated at the beginning and end of the training and control period. Improvements were observed in the training group but not in the control group. Individuals in the training group improved hip flexion strength by 12.2% and decreased their 40-yd and shuttle run times by 3.8% and 9.0%, respectively. An increase in hip flexion strength can help to improve sprint and agility performance for physically active, untrained individuals.     

Thigh-muscles strength training, dance exercise, dynamometry, and anthropometry in professional ballerinas

The purpose of the present study was to assess the effects of 12 weeks of quadriceps and hamstring strength training on torque levels after a dance exercise and on selected anthropometric parameters. The sample consisted of 22 (ages, 25 +/- 1.3 years) full-time professional ballerinas who were randomly assigned into experimental (n = 12) and control (n = 10) groups. A dance routine designed to cause fatigue within 5 minutes, isokinetic dynamometry, and anthropometric assessments were conducted before and after strength training in both groups. Before strength training, the dance routine resulted in significant reductions of hamstring (p < 0.001) and quadriceps (p < 0.001) peak torques in both subject groups. However, after strength training, only control subjects demonstrated such torque decrements (p < 0.001) after the dance routine. Furthermore, the experimental group revealed greater knee extension (119 vs. 138 N.m; p < 0.001) and flexion (60 vs. 69 N.m; p < 0.001) torques, smaller sum of skinfolds (33.6 vs. 27.8 mm; p < 0.01), more fat-free mass (37.7 vs. 39.4 kg; p < 0.05), but unchanged body mass (p > 0.05) and thigh circumferences (p > 0.05). A negative relationship (p < 0.001) was found between initial strength levels and improvements measured at the end of the 12-week program. These results suggest that supplementary strength training for hamstring and quadriceps muscles is beneficial to professional ballerinas and their dancing; weaker individuals are more likely to benefit from such regimens than their stronger counterparts, whereas increases in thigh-muscle strength do not alter selected aesthetic components.     

24-hour, weekly, and annual patterns in traumatic and non-traumatic surgical pediatric emergencies

24 h patterns with high frequency components in the incidence of pediatric trauma were validated and quantified in one of our earlier studies. Herein, we further explored the temporal—high frequency, 24 h, weekly (7 d), hemi-weekly (3.5 d), and annual - patterns in traumatic (1990-1997; n=15,110 events) and non-traumatic pediatric surgical emergencies (PSE) (1992-2001; n=5,593 events) as well as automobile accidents (AA) (1990-1997; n=67,712) in the County of Vaud, Switzerland. The latter served as a reference system of human adult activity and risk. Two-way ANOVA, χ2, correlation, and cosinor analyses were used as statistical tools. A 24 h pattern, reproducible from year to year, was validated in traumatic and non-traumatic PSE and AA. The 24 h patterns were not correlated and differed from one another in terms of their acrophase (peak time) and amplitude. A gender-related difference was found only in the non-traumatic time series for weekly (7 d) and hemi-weekly (3.5 d) patterns. The latter were detected in boys but not girls. No statistically significant difference was found in the acrophase and amplitude between boys and girls in the temporal patterns of other periods. An annual pattern was validated in automobile accidents (acrophase: 4th of September ±37 d (SD)) and pediatric trauma (acrophase: 14th of June ±10 d), but not in non-traumatic PSE. These results suggest that environmental modulations differ between the incidence of traumatic and non-traumatic PSE. Presumably, the two phenomena involve different aspects of the temporal organization and/or different levels of susceptibility of a set of biological rhythms to environmental factors.     

The effect of a change in sleep-wakefulness timing, bright light and physical exercise interventions on 24-hour patterns of performance, mood and body temperature

Experiments consisting of baseline, bright light and physical exercise studies were carried out to compare the effect of a 9-hour delay in sleep-wakefulness timing, and the effects of bright light and physical exercise interventions on 24-hour patterns of performance, mood and body temperature were examined. Each study comprised a 24-hour constant routine at the beginning followed by 3 night shifts and 24-hour constant routine at the end. Performance on tasks differing in cognitive load, mood and body temperature was measured during each constant routine and the interventions were applied during the night shifts. The 24-hour pattern of alertness and performance on the tasks with low cognitive load in post-treatment conditions followed the change in sleep-wakefulness timing while more cognitively loaded tasks tended to show a reverse trend when compared to pre-treatment conditions. There was a phase delay around 4 hours in circadian rhythms of body temperature in post-treatment conditions.     

Inter-session reliability and sex-related differences in hamstrings total reaction time,pre-motor time and motor time during eccentric isokinetic contractions in recreational athlete

The purposes were twofold: (a) to ascertain the inter-session reliability of hamstrings total reaction time, pre-motor time and motor time; and (b) to examine sex-related differences in the hamstrings reaction times profile. Twenty-four men and 24 women completed the study. Biceps femoris and semitendinosus total reaction time, pre-motor time and motor time measured during eccentric isokinetic contractions were recorded on three different occasions. Inter-session reliability was examined through typical percentage error (CV_TE), percentage change in the mean (CM) and intraclass correlations (ICC). For both biceps femoris and semitendinosus, total reaction time, pre-motor time and motor time measures demonstrated moderate inter-session reliability (CV_TE < 10%; CM < 3%; ICC > 0.7). The results also indicated that, although not statistically significant, women reported consistently longer hamstrings total reaction time (23.5 ms), pre-motor time (12.7 ms) and motor time (7.5 ms) values than men. Therefore, an observed change larger than 5%, 9% and 8% for total reaction time, pre-motor time and motor time respectively from baseline scores after performing a training program would indicate that a real change was likely. Furthermore, while not statistically significant, sex differences were noted in the hamstrings reaction time profile which may play a role in the greater incidence of ACL injuries in women.     

24-hour changes in ACTH, corticosterone, growth hormone, and leptin levels in young male rats subjected to calorie restriction

Calorie restriction of young male rats increases plasma prolactin, decreases luteinizing hormone (LH) and testosterone, and disrupts their 24 h secretory pattern. To study whether this could be the consequence of stress, we examined the 24 h variations of plasma adrenocorticotropic hormone (ACTH) corticosterone, growth hormone (GH), leptin, and adrenal corticosterone. Rats were submitted to a calorie restriction equivalent to a 66% of usual intake for 4 weeks, starting on day 35 of life. Controls were kept in individual cages and allowed to eat a normal calorie regimen. Significantly lower ACTH levels were detected in calorie-restricted rats. Plasma corticosterone levels during the light phase of the daily cycle were significantly higher in calorie-restricted rats. Time-of-day variation in plasma ACTH and corticosterone levels attained significance in calorie-restricted rats only, with a maximum toward the end of the resting phase. The daily pattern of adrenal gland corticosterone mirrored that of circulating corticosterone; however, calorie restriction reduced its levels. Plasma ACTH and corticosterone correlated significantly in controls only. Calorie restriction decreased plasma GH and leptin, and it distorted 24 h rhythmicity. In a second study, plasma ACTH and corticosterone levels were measured in group-caged rats, isolated control rats, and calorie-restricted rats during the light phase of the daily cycle. Plasma ACTH of calorie-restricted rats was lower, and plasma corticosterone was higher, compared with isolated or group-caged controls. The changes in the secretory pattern of hormones hereby reported may be part of the neuroendocrine and metabolic mechanisms evolved to maximize survival during periods of food shortage.     

Relationship between clinical, 24-hour, average day-time and night-time blood pressure and measures of arterial stiffness in essential hypertension

Arterial wall stiffness is considered an independent cardiovascular risk factor. Aim of this study was to evaluate relationship between clinical, 24-hour, average day-time and night-time blood pressure (BP) and measures of arterial stiffness assessed by pulse wave velocity (PWV) (using SphygmoCor applanation tonometer) in essential hypertension (severe-resistant (RH, n=29) and moderate hypertension (EH, n=35)) and in normotensive control subjects (n-29) (NCS) matched by age. After multiple regression analysis, PWV remains significantly correlated mainly with night-time pulse pressure and to a lesser extent with age. PWV was significantly higher in RH compared to moderate EH and NCS.     

An eight-week golf-specific exercise program improves physical characteristics, swing mechanics, and golf performance in recreational golfers

The purpose of this study was to determine the effects of an 8-week golf-specific exercise program on physical characteristics, swing mechanics, and golf performance. Fifteen trained male golfers (47.2 +/- 11.4 years, 178.8 +/- 5.8 cm, 86.7 +/- 9.0 kg, and 12.1 +/- 6.4 U.S. Golf Association handicap) were recruited. Trained golfers was defined operationally as golfers who play a round of golf at least 2-3 times per week and practice at the driving range at least 2-3 times per week during the regular golf season. Subjects performed a golf-specific conditioning program 3-4 times per week for 8 weeks during the off-season in order to enhance physical characteristics. Pre- and posttraining testing of participants included assessments of strength (torso, shoulder, and hip), flexibility, balance, swing mechanics, and golf performance. Following training, torso rotational strength and hip abduction strength were improved significantly (p < 0.05). Torso, shoulder, and hip flexibility improved significantly in all flexibility measurements taken (p < 0.05). Balance was improved significantly in 3 of 12 measurements, with the remainder of the variables demonstrating a nonsignificant trend for improvement. The magnitude of upper-torso axial rotation was decreased at the acceleration (p = 0.015) and impact points (p =0.043), and the magnitude of pelvis axial rotation was decreased at the top (p = 0.031) and acceleration points (p = 0.036). Upper-torso axial rotational velocity was increased significantly at the acceleration point of the golf swing (p = 0.009). Subjects increased average club velocity (p = 0.001), ball velocity (p = 0.001), carry distance (p = 0.001), and total distance (p = 0.001). These results indicate that a golf-specific exercise program improves strength, flexibility, and balance in golfers. These improvements result in increased upper-torso axial rotational velocity, which results in increased club head velocity, ball velocity, and driving distance.     

A half-marathon and a marathon run induce oxidative DNA damage, reduce antioxidant capacity to protect DNA against damage and modify immune function in hobby runners

This study investigated whether a 21.1 km (half-marathon) or a 42.195 km (marathon) run modulates DNA damage, antioxidant capacity in lymphocytes and plasma, and the immune system in healthy hobby runners. Ten and 12 volunteers who completed the Baden-Marathon race in Karlsruhe with a running distance of 21.1 km and 41.195 km, respectively, were assessed 10 days before and immediately after the finish. There was no increase in the levels of endogenous DNA strand breaks immediately after half-marathon or marathon races. A statistically significant increase in the levels of oxidative DNA damage in lymphocytes was found using endonuclease III but not formamidopyrimidine glycolase (Fpg). The resistance of DNA to oxidative damage induced by hydrogen peroxide in isolated lymphocytes was significantly decreased after both races. The levels of plasma antioxidants such as alpha-tocopherol, beta-carotene and lycopene were close to, or higher than, those considered optimal for reducing the risk of cardiovascular diseases and there were no significant changes after the races in antioxidant capacity of LDL (lag-time test) or plasma in ORAC, TEAC or paraoxonase assays. The number and percentage of granulocytes and monocytes able to generate oxidative burst were significantly increased after both races, but the lytic activity of NK cells was significantly increased at the end of the half-marathon; no effect was observed in the marathon runners. Thus, oxidative DNA damage in lymphocytes, decreased the antioxidant capacity to protect lymphocytes against DNA strand breaks and increased the formation of reactive species by phagocytes in well-nourished hobby runners indicating moderate oxidative damage during such high-intensity exercise.     

24-hour changes in circulating prolactin, follicle-stimulating hormone, luteinizing hormone, and testosterone in young male rats subjected to calorie restriction

This work analyzes the effect of calorie restriction on the 24 h variation of pituitary-testicular function in young male Wistar rats by measuring the circulating levels of prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone. Control animals were provided an equilibrium calorie diet and the experimental animals a calorie-restriction diet equivalent to 66% of food restriction for four weeks starting on day 35 of life. Different groups of control and experimental rats were killed at 6 h intervals around the clock, beginning 1 h after light on (HALO). Compared to the control animals, the mean secretion of prolactin was augmented and that of LH and testosterone decreased in calorie-restricted rats, whereas FSH release remained unchanged. Significant changes in the 24 h secretory pattern of circulating prolactin, LH, and testosterone occurred in the calorie-restricted rats. These include the appearance of a second maximum of plasma prolactin at 21 HALO, blunting of the LH peak seen at 13 HALO, and phase-shift of the testosterone peak from 13 HALO in controls to 17 HALO in calorie-restricted rats. The significant positive correlation between individual LH and testosterone levels found in controls was no longer observed in calorie-restricted rats. Availability of nutrients presumably affects the mechanisms that modulate the circadian variation of the pituitary-gonadal axis in growing male rats.     

Prospective evaluation of cardiac effects of first-time marathon training,running, and recovery in middle-aged men: cohort study rationale and design

BackgroundSeveral phenomena may point to potentially detrimental cardiac effects of endurance exercise, such as elevated circulating cardiac troponin levels and reductions in systolic and diastolic function directly after marathon completion. Furthermore, while myocardial abnormalities have been reported in patients who recovered from COVID-19, the cardiac impact of extensive endurance exercise in individuals who recovered from COVID-19 remains unknown. We therefore aim to investigate (potentially detrimental) cardiac effects of first-time marathon training and participation, including a subset of participants who recovered from COVID-19, in apparently healthy middle-aged men.Study designThis exploratory prospective cohort study investigates cardiac effects of first-time marathon running in 24 middle-aged (35–50 years) healthy men. Primary outcomes are cardiac morphological changes from pre-training up to 1 month after marathon completion, measured with magnetic resonance imaging (MRI) at 4 time points: 1) baseline (4 months before the marathon), 2) pre-marathon (2 weeks before the marathon), 3) post-marathon (< 24 h post-marathon), and 4) recovery (4 weeks after the marathon). Secondary parameters include other cardiac or non-cardiac changes: 1) quantitative MRI myocardial mapping, including mean diffusivity and extracellular volume fraction, 2) echocardiographic morphology and function changes, 3) VO₂max, 4) electrocardiogram changes, and 5) levels of cardiac biomarkers.DiscussionThis study will contribute to our understanding of cardiac adaptations and maladaptations to first-time marathon running in middle-aged men, and the interaction between extreme endurance exercise and potential detrimental cardiac effects, also in the context of COVID-19. Results will inform on future research directions while providing new clinical insights for health professionals involved in athlete care.     

Growth, reproduction and activity rhythms in two species of edible snails, Helix aspersa and Helix lucorum, in non 24-hour light cycles

Both juvenile and adult Helix aspera and H. lucorum showed significant periodicities in locomotor activity close to an imposed 24-h die1 of 13L: 11D, and to 20 diels of 13L:7D and 11L: 9D. Helix aspersa is active earlier in the night in 24-h diels than H. lucorum . In both 20-h diels H. aspersa showed a lag in attaining peak activity. We discuss the fact that H. aspersa copes better with 13L:7D and H. lucorum copes better with 11L:9D. Although both of them seem to grow faster in the 24-h diel, H. lucorum is indifferent to photoperiod in relation to its growth. Helix aspersa became mature in four months in all the three regimes, but its size and maturity were influenced by the three photoperiod regimes. Egg-laying was also influenced by the photoperiod regimes, but hatching was not.     

Serum testosterone concentration in response to exogenous GnRH does not predict service rates or pregnancy rates by yearling, performance tested, crossbred bulls

Ten bulls with a scrotal circumference of less than 30 cm at the end of growth performance testing, and 10 cohorts of the same age, size and breed type with a scrotal circumference greater than 30 cm were used to evaluate if testosterone response following GnRH administration could be used to test for fertility, for semen quality, and for specific pathologic testicular parenchymal changes. Serum testosterone concentrations were determined immediately before and 2 to 3 hours following intramuscular injection of 250 ug GnRH. Bulls were examined for breeding soundness, then fertility was tested in a breeding trial; testicular histology was assessed by determining the percentage of cross-sections of seminiferous tubules with no spermatocytes. The mean (+/- SEM) post-GnRH serum testosterone concentration for all bulls was 11.71 (+/-0.64) ng/ml. In order to examine for an association, the GnRH response was classified as above or below the mean for resultant serum testosterone concentration. The GnRH response classification was not related to the scrotal circumference, percentage of tubules devoid of spermatocytes, or percentage of progressively motile spermatozoa (P > 0.10). The percentage of morphologically normal spermatozoa was significantly higher (P < 0.05) in the bulls with a higher than mean testosterone secretion in response to GnRH injection. In the breeding trial, the percentage of heifers bred and the percentage of heifers pregnant (60 days post breeding) were not significantly different (P > 0.10) between the 2 classifications of GnRH response. The GnRH response test was related to the percentage of morphologically normal spermatozoa but did not predict fertility of yearling bulls in this study.     

Trait plasticity,not values,best corresponds with woodland plant success in novel and manipulated habitats

Aims The clustering of plants with similar leaf traits along environmental gradients may arise from adaptation as well as acclimation to heterogeneous habitat conditions. Determining the forces that shape plant leaf traits requires both linking variation in trait morphology with abiotic gradients and linking that trait variation with plant performance under varying abiotic conditions. Across the spectrum of plant types, shade-tolerant evergreen herbs are relatively low in trait plasticity, compared to deciduous and sun-adapted species. These plants employ stress-tolerant strategies for survival, which coincide with relatively static trait morphologies, slow growth and hence a lower ability to adjust to changing environmental conditions.Methods We investigate how the survival of two ecologically similar understory evergreen species, Asarum arifolium and Hepatica nobilis, corresponds with variation in six commonly measured functional traits (leaf area, specific leaf area, plant height, leaf number, leaf length and shoot mass) along natural and experimental abiotic gradients. We examine temporal (the period 2007–9) and spatial (100 km) variations in these traits after (i) translocating 576 plants across a span from the southern Appalachian Mountains in NC, USA, to the Piedmont, GA, USA, which includes north- and south-facing slope habitats and (ii) the experimental manipulation of diffuse light and soil moisture.Important findings We find that when translocated into a novel habitats, with novel environmental conditions that often are more extreme than the source habitat, both species appear capable of considerable morphological acclimation and generally converge to similar trait values. Hepatica nobilis does not exhibit mean trait values particularly different from those of A. arifolium, but it demonstrates much greater phenotypic plasticity. These results indicate that relatively conservative plant species nonetheless acclimate and survive across heterogeneous environmental conditions.     

Volume and density of microglomeruli in the honey bee mushroom bodies do not predict performance on a foraging task

The mushroom bodies (MBs) are insect brain regions important for sensory integration, learning, and memory. In adult worker honey bees (Apis mellifera ), the volume of neuropil associated with the MBs is larger in experienced foragers compared with hive bees and less experienced foragers. In addition, the characteristic synaptic structures of the calycal neuropils, the microglomeruli, are larger but present at lower density in 35‐day‐old foragers relative to 1‐day‐old workers. Age‐ and experience‐based changes in plasticity of the MBs are assumed to support performance of challenging tasks, but the behavioral consequences of brain plasticity in insects are rarely examined. In this study, foragers were recruited from a field hive to a patch comprising two colors of otherwise identical artificial flowers. Flowers of one color contained a sucrose reward mimicking nectar; flowers of the second were empty. Task difficulty was adjusted by changing flower colors according to the principle of honey bee color vision space. Microglomerular volume and density in the lip (olfactory inputs) and collar (visual inputs) compartments of the MB calyces were analyzed using anti‐synapsin I immunolabeling and laser scanning confocal microscopy. Foragers displayed significant variation in microglomerular volume and density, but no correlation was found between these synaptic attributes and foraging performance. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1057–1071, 2017