Optimal stride frequencies in running at different speeds

During running at a constant speed, the optimal stride frequency (SF) can be derived from the u-shaped relationship between SF and heart rate (HR). Changing SF towards the optimum of this relationship is beneficial for energy expenditure and may positively change biomechanics of running. In the current study, the effects of speed on the optimal SF and the nature of the u-shaped relation were empirically tested using Generalized Estimating Equations. To this end, HR was recorded from twelve healthy (4 males, 8 females) inexperienced runners, who completed runs at three speeds. The three speeds were 90%, 100% and 110% of self-selected speed. A self-selected SF (SFself) was determined for each of the speeds prior to the speed series. The speed series started with a free-chosen SF condition, followed by five imposed SF conditions (SFself, 70, 80, 90, 100 strides·min-1) assigned in random order. The conditions lasted 3 minutes with 2.5 minutes of walking in between. SFself increased significantly (p<0.05) with speed with averages of 77, 79, 80 strides·min-1 at 2.4, 2.6, 2.9 m·s-1, respectively). As expected, the relation between SF and HR could be described by a parabolic curve for all speeds. Speed did not significantly affect the curvature, nor did it affect optimal SF. We conclude that over the speed range tested, inexperienced runners may not need to adapt their SF to running speed. However, since SFself were lower than the SFopt of 83 strides·min-1, the runners could reduce HR by increasing their SFself

Phase 3 Randomized Trial of Prophylactic Cranial Irradiation With or Without Hippocampus Avoidance in SCLC (NCT01780675)

Introduction: To compare neurocognitive functioning in patients with SCLC who received prophylactic cranial irradiation (PCI) with or without hippocampus avoidance (HA). Methods: In a multicenter, randomized phase 3 trial (NCT01780675), patients with SCLC were randomized to standard PCI or HA-PCI of 25 Gy in 10 fractions. Neuropsychological tests were performed at baseline and 4, 8, 12, 18, and 24 months after PCI. The primary end point was total recall on the Hopkins Verbal Learning Test-Revised at 4 months; a decline of at least five points from baseline was considered a failure. Secondary end points included other cognitive outcomes, evaluation of the incidence, location of brain metastases, and overall survival. Results: From April 2013 to March 2018, a total of 168 patients were randomized. The median follow-up time was 26.6 months. In both treatment arms, 70% of the patients had limited disease and baseline characteristics were well balanced. Decline on the Hopkins Verbal Learning Test-Revised total recall score at 4 months was not significantly different between the arms: 29% of patients on PCI and 28% of patients on HA-PCI dropped greater than or equal to five points (p = 1.000). Performance on other cognitive tests measuring memory, executive function, attention, motor function, and processing speed did not change significantly different over time between the groups. The overall survival was not significantly different (p = 0.43). The cumulative incidence of brain metastases at 2 years was 20% (95% confidence interval: 12%-29%) for the PCI arm and 16% (95% confidence interval: 7%-24%) for the HA-PCI arm. Conclusions: This randomized phase 3 trial did not find a lower probability of cognitive decline in patients with SCLC receiving HA-PCI compared with conventional PCI. No increase in brain metastases at 2 years was observed in the HA-PCI arm. (C) 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved

Effects of fatigue on trunk stability in elite gymnasts

The aim of the present study was to test the hypothesis that fatigue due to exercises performed in training leads to a decrement of trunk stability in elite, female gymnasts. Nine female gymnasts participated in the study. To fatigue trunk muscles, four series of five dump handstands on the uneven bar were performed. Before and after the fatigue protocol, participants performed three trials of a balancing task while sitting on a seat fixed over a hemisphere to create an unstable surface. A force plate tracked the location of the center of pressure (CoP). In addition, nine trials were performed in which the seat was backward inclined over a set angle and suddenly released after which the subject had to regain balance. Sway amplitude and frequency in unperturbed sitting were determined from the CoP time series and averaged over trials. The maximum displacement and rate of recovery of the CoP location after the sudden release were determined and averaged over trials. After the fatigue protocol, sway amplitude in the fore-aft direction was significantly increased (p = 0.03), while sway frequency was decreased (p = 0.005). In addition, the maximum displacement after the sudden release was increased (p = 0.009), while the rate of recovery after the perturbation was decreased (p = 0.05). Fatigue induced by series of exercises representing a realistic training load caused a measurable decrement in dynamic stability of the trunk in elite gymnasts

Resectability and Ablatability Criteria for the Treatment of Liver Only Colorectal Metastases:Multidisciplinary Consensus Document from the COLLISION Trial Group

The guidelines for metastatic colorectal cancer crudely state that the best local treatment should be selected from a 'toolbox' of techniques according to patient- and treatment-related factors. We created an interdisciplinary, consensus-based algorithm with specific resectability and ablatability criteria for the treatment of colorectal liver metastases (CRLM). To pursue consensus, members of the multidisciplinary COLLISION and COLDFIRE trial expert panel employed the RAND appropriateness method (RAM). Statements regarding patient, disease, tumor and treatment characteristics were categorized as appropriate, equipoise or inappropriate. Patients with ECOG≤2, ASA≤3 and Charlson comorbidity index ≤8 should be considered fit for curative-intent local therapy. When easily resectable and/or ablatable (stage IVa), (neo)adjuvant systemic therapy is not indicated. When requiring major hepatectomy (stage IVb), neo-adjuvant systemic therapy is appropriate for early metachronous disease and to reduce procedural risk. To downstage patients (stage IVc), downsizing induction systemic therapy and/or future remnant augmentation is advised. Disease can only be deemed permanently unsuitable for local therapy if downstaging failed (stage IVd). Liver resection remains the gold standard. Thermal ablation is reserved for unresectable CRLM, deep-seated resectable CRLM and can be considered when patients are in poor health. Irreversible electroporation and stereotactic body radiotherapy can be considered for unresectable perihilar and perivascular CRLM 0-5cm. This consensus document provides per-patient and per-tumor resectability and ablatability criteria for the treatment of CRLM. These criteria are intended to aid tumor board discussions, improve consistency when designing prospective trials and advance intersociety communications. Areas where consensus is lacking warrant future comparative studies.</p

Identification of elderly fallers by muscle strength measures

For efficient prevention of falls among older adults, individuals at a high risk of falling need to be identified. In this study, we searched for muscle strength measures that best identified those individuals who would fall after a gait perturbation and those who recovered their balance. Seventeen healthy older adults performed a range of muscle strength tests. We measured maximum and rate of development of ankle plantar flexion moment, knee extension moment and whole leg push-off force, as well as maximum jump height and hand grip strength. Subsequently, their capacity to regain balance after tripping over an obstacle was determined experimentally. Seven of the participants were classified as fallers based on the tripping outcome. Maximum isometric push-off force in a leg press apparatus was the best measure to identify the fallers, as cross-validation of a discriminant model with this variable resulted in the best classification (86% sensitivity and 90% specificity). Jump height and hand grip strength were strongly correlated to leg press force (r = 0.82 and 0.59, respectively) and can also be used to identify fallers, although with slightly lower specificity. These results indicate that whole leg extension strength is associated with the ability to prevent a fall after a gait perturbation and might be used to identify the elderly at risk of falling

B-cell targeting with anti-CD38 daratumumab:implications for differentiation and memory responses

B cell–targeted therapies, such as CD20-targeting mAbs, deplete B cells but do not target the autoantibody-producing plasma cells (PCs). PC-targeting therapies such as daratumumab (anti-CD38) form an attractive approach to treat PC-mediated diseases. CD38 possesses enzymatic and receptor capabilities, which may impact a range of cellular processes including proliferation and differentiation. However, very little is known whether and how CD38 targeting affects B-cell differentiation, in particular for humans beyond cancer settings. Using in-depth in vitro B-cell differentiation assays and signaling pathway analysis, we show that CD38 targeting with daratumumab demonstrated a significant decrease in proliferation, differentiation, and IgG production upon T cell–dependent B-cell stimulation. We found no effect on T-cell activation or proliferation. Furthermore, we demonstrate that daratumumab attenuated the activation of NF-?B in B cells and the transcription of NF-?B–targeted genes. When culturing sorted B-cell subsets with daratumumab, the switched memory B-cell subset was primarily affected. Overall, these in vitro data elucidate novel non-depleting mechanisms by which daratumumab can disturb humoral immune responses. Affecting memory B cells, daratumumab may be used as a therapeutic approach in B cell–mediated diseases other than the currently targeted malignancies

Response perseveration and ventral prefrontal sensitivity to reward and punishment in male problem gamblers and smokers

Pathological gambling (PG) is associated with maladaptive perseverative behavior, but the underlying mechanism and neural circuitry is not completely clear. Here, the hypothesis was tested that PG is characterized by response perseveration and abnormalities in reward and/or punishment sensitivity in the ventral frontostriatal circuit. Executive functioning was assessed to verify if these effects are independent of the dorsal frontostriatal circuit. A group of smokers was also included to examine whether impairments in PG generalize to substance use disorders. Response perseveration and reward/punishment sensitivity were measured with a probabilistic reversal-learning task, in which subjects could win and lose money. Executive functioning was measured with a planning task, the Tower of London. Performance and fMRI data were acquired in 19 problem gamblers, 19 smokers, and 19 healthy controls. Problem gamblers showed severe response perseveration, associated with reduced activation of right ventrolateral prefrontal cortex in response to both monetary gain and loss. Results did not fully generalize to smokers. Planning performance and related activation of the dorsal frontostriatal circuit were intact in both problem gamblers and smokers. PG is related to response perseveration and diminished reward and punishment sensitivity as indicated by hypoactivation of the ventrolateral prefrontal cortex when money is gained and lost. Moreover, intact planning abilities and normal dorsal frontostriatal responsiveness indicate that this deficit is not due to impaired executive functioning. Response perseveration and ventral prefrontal hyporesponsiveness to monetary loss may be markers for maladaptive behavior seen in chemical and nonchemical addictions. © 2009 Nature Publishing Group All rights reserved

Guideline for diagnosis and treatment of subacromial pain syndrome

Treatment of "subacromial impingement syndrome" of the shoulder has changed drastically in the past decade. The anatomical explanation as "impingement" of the rotator cuff is not sufficient to cover the pathology. "Subacromial pain syndrome", SAPS, describes the condition better. A working group formed from a number of Dutch specialist societies, joined by the Dutch Orthopedic Association, has produced a guideline based on the available scientific evidence. This resulted in a new outlook for the treatment of subacromial pain syndrome. The important conclusions and advice from this work are as follows: (1) The diagnosis SAPS can only be made using a combination of clinical tests. (2) SAPS should preferably be treated non-operatively. (3) Acute pain should be treated with analgetics if necessary. (4) Subacromial injection with corticosteroids is indicated for persistent or recurrent symptoms. (5) Diagnostic imaging is useful after 6 weeks of symptoms. Ultrasound examination is the recommended imaging, to exclude a rotator cuff rupture. (6) Occupational interventions are useful when complaints persist for longer than 6 weeks. (7) Exercise therapy should be specific and should be of low intensity and high frequency, combining eccentric training, attention to relaxation and posture, and treatment of myofascial trigger points (including stretching of the muscles) may be considered. (8) Strict immobilization and mobilization techniques are not recommended. (9) Tendinosis calcarea can be treated by shockwave (ESWT) or needling under ultrasound guidance (barbotage). (10) Rehabilitation in a specialized unit can be considered in chronic, treatment resistant SAPS, with pain perpetuating behavior. (11) There is no convincing evidence that surgical treatment for SAPS is more effective than conservature management. (12) There is no indication for the surgical treatment of asymptomatic rotator cuff tears

Stride and Step Length Obtained with Inertial Measurement Units during Maximal Sprint Acceleration

During sprint acceleration, step length, step rate, ground contact, and airtime are key variables for coaches to guide the training process and technical development of their athletes. In the field, three of these variables are easily obtained with inertial measurement units (IMUs), but, unfortunately, valid estimates of step length with IMUs currently are limited to low speeds ( 0.05) and acceptable agreement (root mean square error, RMSE = 8.0 cm, bias ± Limits of Agreement = -0.15 ± 16 cm). Step length estimations further improved (RMSE = 5.7 cm, -0.16 ± 11 cm) after smoothing the original estimated step lengths with a third order polynomial function (R2 = 0.94 ± 0.04). In conclusion, during maximal sprint acceleration, acceptable estimates of stride and step length were obtained from IMU-derived step times and 30-m (split) and 60-m sprint times