Immune checkpoint inhibitor toxicity and associated outcomes in older patients with cancer.

INTRODUCTION: Increased immune checkpoint inhibitor (ICI) use in various advanced cancer types has led to a parallel rise in immune-related adverse events (irAEs). Despite widespread use, ICI data in older patients remains limited. We investigate irAE prevalence in older patients receiving ICI and whether irAEs and survival are associated. MATERIALS AND METHODS: Our retrospective study included patients aged ≥65 years with advanced malignancies who had ≥1 dose of ICI from January 2011 through September 2019. We evaluated irAE cases and their respective grades and assessed oncological response by progression-free survival (PFS) and overall survival (OS). RESULTS: Mean age of 210 patients was 75.0 ± 7.2 years, 58.1% were men, and most were white. IrAE prevalence was 41.4% (n = 87); 9.5% (n = 20) developed multisystem irAE. Most irAEs were grades 1 and 2 (27.6% and 49.4%, respectively), while grades 3 and 4 accounted for 17.2% and 5.8%, respectively. No grade 5 irAE occurred. Compared with patients with no irAEs, those with irAEs had improved OS (HR [hazard ratio], 0.41; 95% CI [confidence interval], 0.282-0.597; p < 0.0001) and PFS (HR, 0.311; 95% CI: 0.213-0.453; p < 0.0001). Improved OS was seen with irAE grades 1 and 2 versus grades 3 and 4 (HR, 0.344; 95% CI: 0.171-0.694; p = 0.0029). Similarly, improved PFS was seen with lower grade irAE (HR, 0.489; 95% CI: 0.247-0.965; p = 0.0391). DISCUSSION: The irAE prevalence in older patients was similar to that in younger patients. To our knowledge, this is one of few studies that confirms a positive association of irAE on both OS and PFS in older patients with cancer, and improved OS and PFS with lower versus higher grade irAE.

Relative Contributions of Handgrip and Individual Finger Strength on Climbing Performance in a Bouldering Competition.

PURPOSE: To determine the relative contributions of handgrip and individual finger strength for the prediction of climbing performance in a bouldering competition. A secondary aim was to examine the influence of body size, bouldering experience, and training habits. METHODS: Sixty-seven boulderers (mean [SD], age = 21.1 [4.0] y; body mass = 69.5 [9.8] kg) volunteered for this study. Data collection occurred immediately before an indoor bouldering competition and involved the assessment of handgrip and individual finger maximal force production using an electronic handheld dynamometer. The bouldering competition consisted of 70 routes graded V0 to V8, with higher point values awarded for completing more difficult routes. Stepwise multiple regression analysis was used to examine the relative contributions of handgrip and individual finger strengths, body mass, height, bouldering experience, and bouldering frequency to the prediction of performance scores in the competition. RESULTS: Ring finger pinch strength, bouldering experience, and bouldering frequency significantly (P < .05) contributed to the model (R2 = .373), whereas body mass; height; full handgrip strength, as well as index, middle, and little finger pinch strengths did not. The ß weights showed that ring finger pinch strength (ß = .430) was the most significant contributor, followed by bouldering experience (ß = .331) and bouldering frequency (ß = .244). CONCLUSIONS: The current findings indicated that trainable factors contributed to the prediction of bouldering performance. These results suggest greater bouldering frequency and experience likely contribute to greater isolated individual finger strength, thereby optimizing preparation for the diverse handholds in competitive rock climbing.

Application of the neuromuscular fatigue threshold treadmill test to muscles of the quadriceps and hamstrings.

PURPOSE: The purposes of the present study were: (1) to determine whether the physical working capacity at the fatigue threshold (PWCFT) model that has been used for estimating the onset of neuromuscular fatigue in the vastus lateralis (VL) during incremental treadmill running could also be applied to the vastus medialis (VM), biceps femoris (BF), and semitendinosus (ST) muscles; and (2) if applicable, to compare the running velocities associated with the PWCFT among these muscles. METHODS: Eleven subjects (age 21.7 ± 1.8 years) performed an incremental treadmill test to exhaustion with electromyographic signals recorded from the VL, VM, BF, and ST. RESULTS: The results indicated there were no significant (p > 0.05) mean differences in the running velocities associated with the PWCFT for the VL (14.4 ± 2.0 km/h), VM (14.3 ± 1.9 km/h), BF (13.8 ± 1.8 km/h), and ST (14.7 ± 2.3 km/h). In addition, there were significant inter-correlations (r = 0.68-0.88) among running velocities associated with the PWCFT of each muscle. Individual results also indicated that 9 of the 11 subjects exhibited identical PWCFT values for at least 3 of the 4 muscles, but there were no uniform patterns for any intra-individual differences. CONCLUSION: The findings of the present study suggested that the PWCFT test is a viable method to identify neuromuscular fatigue in the quadriceps and hamstrings during incremental treadmill exercise and results in consistent PWCFT values among these muscles.

Accessing interpersonal and intrapersonal coordination dynamics.

Both intrapersonal and interpersonal coordination dynamics have traditionally been investigated using relative phase patterns of in-phase (ϕ = 0°) and/or anti-phase (ϕ = 180°). Numerous investigations have demonstrated that coordination tasks that require other relative phase patterns (e.g., 90°) are difficult or near impossible to perform without extended practice. Recent findings, however, have demonstrated that an individual can produce a wide range of intrapersonal bimanual patterns within a few minutes of practice when provided integrated feedback. The present experiment was designed to directly compare intra- and interpersonal coordination performance and variability when provided Lissajous feedback or pacing metronome. Single participants (N = 12) and pairs of participants (N = 24, 12 pairs) were required to produce relative phase patterns between 0° and 180° in 30° increments using either pacing metronomes or Lissajous displays. The Lissajous displays involved a goal template and a cursor providing integrated feedback regarding the position of the two effectors. The results indicated both single and pairs of participants could effectively produce a large range of coordination patterns that typically act as repellers after only 6 min of practice when provided integrated feedback. However, single participants performed the in-phase coordination pattern more accurately and with less variability than paired participants, regardless of the feedback condition. These results suggest an advantage for intrapersonal coordination when performing in-phase coordination, possibly due to the stabilizing effect occurring via the neuro-muscular linkage between effectors.

Thinking Outside the Block: External Focus of Attention Improves Reaction Times and Movement Preparation Times in Collegiate Track Sprinters.

While focusing attention on external cues (EF) has been shown to enhance performance track and field coaches tend to provide instructions that promote internal focus of attention (IF) during block starts. The aims of this study were to determine: (1) whether promoting EF versus IF would improve reaction time (RT) of sprinters, and (2) if changes occur at the level of central processes during movement preparation (premotor RT) or peripheral processes during movement execution (motor RT). Twelve collegiate track sprinters (age 20.8 ± 1.7) completed three testing sessions under EF, IF, and no focus instruction (NF) conditions. RT was recorded from the left and right blocks. Muscle activation time (EMG) was recorded from the vastus lateralis and gastrocnemius muscles. Mean rear foot RT was significantly shorter (p < 0.0001) under the EF (212.11 ms) compared with the IF (234.21 ms) and NF conditions (236.87 ms). Front foot RT was significantly shorter (p < 0.05) during EF (250.24 ms), compared to IF (266.98 ms) but not shorter than the NF (268.73 ms) condition. Mean premotor RT under the EF condition (157.75 ms) was significantly shorter (p < 0.001) compared with the IF (181.90 ms) and NF (173.60 ms) conditions. No differences were found in motor RT across conditions (p > 0.05). Adopting an EF improves RT during sprint starts. This improvement likely originates from a shortening in movement preparation time, as opposed to a faster excitation contraction coupling of the muscle fibers. These findings could potentially contribute to the development of new coaching methods aimed at improving the starting technique of athletes.

Influence of acute stress on decision outcomes and heuristics.

BACKGROUND: The purpose of this study was to examine the take-the-first (TTF) heuristic and decision outcomes in sports under conditions of no, mental, and physical stress. METHODS: Participants (N.=68) performed 8 video decision-making trials under each of 3 stress conditions: no stress (counting backwards), mental stress (mental serial subtraction), and physical stress (running on treadmill at 13 RPE). Prior to each decision-making trial, participants were exposed to 30 seconds of stress. The decision-making task required participants to watch a video depicting an offensive situation in basketball and then decide what the player with the ball should do next. RESULTS: No differences were found between the 3 stress conditions on TTF frequency, number of options generated, quality of first generated option, or final decision quality. However, participants performing under conditions of no stress and physical stress generated their first option and made their final decision faster than they did when making decisions under mental stress. CONCLUSIONS: Overall, results suggest that mental stress impairs decision speed and that TTF is an ecologically rationale heuristic in dynamic, time-pressured situations.

Muscle activation of the quadriceps and hamstrings during incremental running.

INTRODUCTION: The aim of this study was to determine the patterns of responses for the electromyographic (EMG) amplitude vs. oxygen uptake ( V̇O2 ) relationships from muscles of the quadriceps femoris and hamstrings during incremental treadmill running. METHODS: Twelve men volunteered to perform an incremental test to exhaustion while EMG signals were recorded from the vastus lateralis, vastus medialis, biceps femoris, and semitendinosus muscles. Polynomial regression analyses were used to determine the best model fit for the EMG amplitude vs. V̇O2 relationships. RESULTS: There were significant (P < 0.05) increases in EMG amplitude across V̇O2 for the vastus lateralis (quadratic, R = 0.995), vastus medialis (quadratic, R = 0.997), biceps femoris (cubic, R = 0.999), and semitendinosus (linear, R = 0.992) muscles as well as the hamstrings-to-quadriceps ratio (cubic, R = 0.999). CONCLUSION: These findings indicate that the patterns of responses for muscle activation vs. exercise intensity appear to be unique among muscles of the thigh.

Acute effects of an arginine-based supplement on neuromuscular, ventilatory, and metabolic fatigue thresholds during cycle ergometry.

The purpose of the present study was to examine the effects of an acute dose of an arginine-based supplement on the physical working capacity at the fatigue threshold (PWCFT), lactate threshold (LT), ventilatory threshold (VT), and peak oxygen uptake during incremental cycle ergometry. This study used a double-blinded, placebo-controlled, within-subjects crossover design. Nineteen untrained men (mean age ± SD = 22.0 ± 1.7 years) were randomly assigned to ingest either the supplement (3.0 g of arginine, 300 mg of grape seed extract, and 300 mg of polyethylene glycol) or placebo (microcrystalline cellulose) and performed an incremental test on a cycle ergometer for determination of PWCFT, LT, VT, and peak oxygen uptake. Following a 1-week period, the subjects returned to the laboratory and ingested the opposite substance (either supplement or placebo) prior to completing another incremental test to be reassessed for PWCFT, LT, VT, and peak oxygen uptake. The paired-samples t tests indicated there were significant (P < 0.05) mean differences between the arginine and placebo conditions for the PWCFT (192 ± 42 vs. 168 ± 53 W, respectively) and VT (2546 ± 313 vs. 2452 ± 342 mL·min(-1)), but not the LT (135 ± 26 vs. 138 ± 22 W), absolute peak oxygen uptake (3663 ± 445 vs. 3645 ± 438 mL·min(-1)), or relative peak oxygen uptake (46.5 ± 6.0 vs. 46.2 ± 5.0 mL·kg(-1)·min(-1)). These findings suggested that the arginine-based supplement may be used on an acute basis for delaying the onset of neuromuscular fatigue (i.e., PWCFT) and improving the VT in untrained individuals.

Development of an Anaerobic Sprint Running Test Using a Nonmotorized Treadmill.

The purpose of this study was to determine the test-retest reliability of a newly developed anaerobic sprint running test (ASRT) on a nonmotorized treadmill (NMT). Twenty-six collegiate male athletes (21.2 ± 2.1 years; 181.3 ± 6.5 cm; 79.0 ± 9.3 kg) completed 3 trials of a 25-second maximal effort sprint on an NMT against a workload set to 18% of their individual body mass. Anaerobic power was determined by relative peak power output (PP) and anaerobic capacity was determined by relative mean power output (MP) during the test. Blood lactate (BLa) responses and fatigue index (FI) were also determined. Test-retest reliability was assessed by intraclass correlation coefficients (ICCs) and coefficients of variation (CV%). Results indicated no significant difference between the 3 trials for PP (T1 = 29.95 ± 6.51 W·kg(-1), T2 = 28.57 ± 5.55 W·kg(-1), T3 = 29.47 ± 5.94 W·kg(-1)), MP (T1 = 20.97 ± 3.64 W·kg(-1), T2 = 20.50 ± 3.46 W·kg(-1), T3 = 21.17 ± 3.79 W·kg(-1), and FI (T1 = 55 ± 8%, T2 = 51 ± 8%, T3 = 52 ± 9%). Reliability between the 3 trials for PP (ICC: r = 0.96, CV: 7%) and MP (ICC: r = 0.97, CV: 6%) was considered high. Reliability for FI exhibited an ICC of r = 0.83 (CV: 6%). Postsprint BLa values were not significantly different (p = 0.49) between the 3 trials. Test-retest reliability for postsprint BLa was found to be good (r = 0.68, CV = 8.8%). The results of the study indicate that the ASRT is reliable for assessing PP and MP in highly motivated subjects. In addition, anaerobic testing using the ASRT may be a more sport-specific test to assess anaerobic performance for many coaches and athletes.

An electromyographic-based test for estimating neuromuscular fatigue during incremental treadmill running.

The purposes of the present study were two fold: (1) to determine if the model used for estimating the physical working capacity at the fatigue threshold (PWCFT) from electromyographic (EMG) amplitude data during incremental cycle ergometry could be applied to treadmill running to derive a new neuromuscular fatigue threshold for running, and (2) to compare the running velocities associated with the PWCFT, ventilatory threshold (VT), and respiratory compensation point (RCP). Fifteen college-aged subjects (21.5 ± 1.3 y, 68.7 ± 10.5 kg, 175.9 ± 6.7 cm) performed an incremental treadmill test to exhaustion with bipolar surface EMG signals recorded from the vastus lateralis. There were significant (p < 0.05) mean differences in running velocities between the VT (11.3 ± 1.3 km h(-1)) and PWCFT (14.0 ± 2.3 km h(-1)), VT and RCP (14.0 ± 1.8 km h(-1)), but not the PWCFT and RCP. The findings of the present study indicated that the PWCFT model could be applied to a single continuous, incremental treadmill test to estimate the maximal running velocity that can be maintained prior to the onset of neuromuscular fatigue. In addition, these findings suggested that the PWCFT, like the RCP, may be used to differentiate the heavy from severe domains of exercise intensity.

Bimanual Fitts' tasks: Kelso, Southard, and Goodman, 1979 revisited.

The experiment was designed to replicate and extend to an integrated feedback condition the pattern of movement time results found by Kelso et al. (J Exp Psychol Hum Percept Perform 5:229-238, 1979a, Science 204:1029-1031, 1979b) where the simultaneous movement of one hand to a low ID target and the other to a higher ID target indicated "a tight coordinate coupling between the hands" (p. 229). In the present experiment, a control group was provided feedback that depicted the independent movement of the two limbs under low and higher indexes of difficulty (ID). A Lissajous group was provided integrated feedback in the form of a Lissajous plot. The results indicated a pattern of results for the control and Lissajous groups similar to that found by Kelso et al. for one and two-limb movements to the same difficulty targets. The control group also replicated the finding for two-limb movements to mixed ID tasks. However, the Lissajous group simultaneously produced disparate movement in the mixed target conditions. The results are consistent with recent findings indicating that when provided salient integrated feedback participants can effectively produce disparate movements of the two limbs.

The coding and inter-manual transfer of movement sequences.

The manuscript reviews recent experiments that use inter-manual transfer and inter-manual practice paradigms to determine the coordinate system (visual-spatial or motor) used in the coding of movement sequences during physical and observational practice. The results indicated that multi-element movement sequences are more effectively coded in visual-spatial coordinates even following extended practice, while very early in practice movement sequences with only a few movement elements and relatively short durations are coded in motor coordinates. Likewise, inter-manual practice of relatively simple movement sequences show benefits of right and left limb practice that involves the same motor coordinates while the opposite is true for more complex sequences. The results suggest that the coordinate system used to code the sequence information is linked to both the task characteristics and the control processes used to produce the sequence. These findings have the potential to greatly enhance our understanding of why in some conditions participants following practice with one limb or observation of one limb practice can effectively perform the task with the contralateral limb while in other (often similar) conditions cannot.

The learning of 90° continuous relative phase with and without Lissajous feedback: external and internally generated bimanual coordination.

Results from recent experiments (e.g., Kovacs, Buchanan, & Shea, 2009a-b, 2010a,b) suggest that when salient visual information is presented using Lissajous plots bimanual coordination patterns typically thought to be very difficult to perform without extensive practice can be performed with remarkably low relative phase error and variability with 5min or less of practice. However, when this feedback is removed, performance deteriorates. The purpose of the present experiment was to determine if reducing the frequency of feedback presentation will decrease the participant's reliance on the feedback and will facilitate the development of an internal representation capable of sustaining performance when the Lissajous feedback is withdrawn. The results demonstrated that reduced frequency Lissajous feedback results in very effective bimanual coordination performance on tests with Lissajous feedback available and when feedback is withdrawn. Taken together the present experiments add to the growing literature that supports the notion that salient perceptual information can override some aspects of the system's intrinsic dynamics typically linked to motor output control. Additionally, the present results suggest that the learning of both externally and internally driven bimanual coordination is facilitated by providing reduced frequency Lissajous feedback.

Perceptual and attentional influences on continuous 2:1 and 3:2 multi-frequency bimanual coordination.

Two experiments were conducted to determine if multi-frequency (2:1 and 3:2) coordination between the limbs is enhanced when integrated feedback is provided in the form of Lissajous plots, attention demands are reduced, and attempts to consciously coordinate the limbs are not encouraged. To determine the influence of vision of the limbs, covered and uncovered limb groups were provided online Lissajous feedback. To determine the impact of the Lissajous feedback, a control group that was not provided Lissajous feedback was also tested. The data indicated remarkably effective performances after 5 min of practice when limbs were covered and Lissajous feedback was provided. When Lissajous feedback was provided and vision of the limbs was permitted, performance deteriorated. Performance by the group not provided Lissajous feedback was quite poor. The findings suggest that some of the difficulty associated with producing difficult bimanual coordination patterns are due to the less than optimal perceptual information available in various testing situations and the attentional focus imposed by the participant.

Amplitude differences, spatial assimilation, and integrated feedback in bimanual coordination.

The purpose of the experiment was to determine the influence of Lissajous feedback on 1:1 bimanual coordination patterns (0 degrees , 90 degrees , and 180 degrees phase lags) when the movement amplitudes of the two limbs were different (30 degrees , 60 degrees ). The present data supports the notion that the lead-lag relationship as well as amplitude assimilation observed in the literature can be partially attributed to the visual-perceptual factors present in the testing environment. When participants are provided integrated feedback in the form of Lissajous plots much of the lead-lag and amplitude assimilation effects were eliminated, and relative phase error and variability were also greatly reduced after only 3 min of practice under each condition.

Coding of on-line and pre-planned movement sequences.

Recent experiments have demonstrated that complex multi-element movement sequences were coded in visual-spatial coordinates even after extensive practice, while relatively simple spatial-temporal movement sequences are coded in motor coordinates after a single practice session. The purpose of the present experiment was to determine if the control process rather than the difficulty of the sequence played a role in determining the pattern of effector transfer. To accomplish this, different concurrent feedback conditions were provided to two groups of participants during practice of the same movement sequence. The results indicated that when concurrent visual feedback was provided during the production of the movement, which was thought to encourage on-line control, the participants performed transfer tests with the contra-lateral limb better when the visual-spatial coordinates were reinstated than when the motor coordinates were reinstated. When concurrent visual feedback was not provided, which was thought to encourage pre-planned control, the opposite was observed. The data are consistent with the hypothesis that the mode of control dictates the coordinate system used to code the movement sequence rather than sequence difficulty or stage of practice as has been proposed.

Impossible is nothing: 5:3 and 4:3 multi-frequency bimanual coordination.

The present findings demonstrate that when participants are provided a Lissajous display with cursor indicating the position of the limbs and a template illustrating the desired movement pattern they can rapidly (10 min) and effectively (continuous relative phase errors and variability ~10 degrees ) tune in a difficult 5:3 bimanual coordination pattern and without additional practice re-tune their responding to an equally difficult 4:3 coordination pattern. The findings indicate the extreme difficulty associated with producing complex polyrhythms in previous experiments has been due to split attention when Lissajous feedback has been provided and inability of the participant to detect and correct coordination errors when only provided vision of the limbs. Effective transfer to the 4:3 polyrhythm without previous practice suggests that the perception-action system's capabilities are extensive. The present findings when viewed in the context of recent experiments using similar protocols suggest that much, but not all, of the difficulty associated with producing a variety of bimanual coordination tasks should be viewed in terms of perceptual constraints imposed by the testing environment.

Representation of movement sequences is related to task characteristics.

Recent experiments have produced mixed results in terms of performance when, after learning a sequential task, the same visual-spatial coordinates or the same motor coordinates were reinstated on a subsequent effector transfer test. Given the diversity of tasks and especially sequence characteristics used in previous experiments, the cross-experimental comparison makes inferences and unambiguous interpretations difficult. The purpose of the present experiment was to determine in a principled manner how the spatio-temporal structure of a sequence influences the way the sequence is represented. The results indicated that after limited amount of practice relatively more simple sequences (S1) are coded more efficiently in a mirror (motor) representation which requires the same pattern of homologous muscle activation. Conversely, relatively more complex sequences (S2) are more efficiently coded in a visual-spatial coordinate system which requires movements to the same spatial locations as during acquisition. The data are also consistent with the notion that sequences with different spatio-temporal structures rely to a different degree on distinct control mechanisms (pre-planned vs. on-line, respectively).