Chronic Lymphocytic Leukemia Therapy Guided by Measurable Residual Disease.

BACKGROUND: The combination of ibrutinib and venetoclax has been shown to improve outcomes in patients with chronic lymphocytic leukemia (CLL) as compared with chemoimmunotherapy. Whether ibrutinib-venetoclax and personalization of treatment duration according to measurable residual disease (MRD) is more effective than fludarabine-cyclophosphamide-rituximab (FCR) is unclear. METHODS: In this phase 3, multicenter, randomized, controlled, open-label platform trial involving patients with untreated CLL, we compared ibrutinib-venetoclax and ibrutinib monotherapy with FCR. In the ibrutinib-venetoclax group, after 2 months of ibrutinib, venetoclax was added for up to 6 years of therapy. The duration of ibrutinib-venetoclax therapy was defined by MRD assessed in peripheral blood and bone marrow and was double the time taken to achieve undetectable MRD. The primary end point was progression-free survival in the ibrutinib-venetoclax group as compared with the FCR group, results that are reported here. Key secondary end points were overall survival, response, MRD, and safety. RESULTS: A total of 523 patients were randomly assigned to the ibrutinib-venetoclax group or the FCR group. At a median of 43.7 months, disease progression or death had occurred in 12 patients in the ibrutinib-venetoclax group and 75 patients in the FCR group (hazard ratio, 0.13; 95% confidence interval [CI], 0.07 to 0.24; P<0.001). Death occurred in 9 patients in the ibrutinib-venetoclax group and 25 patients in the FCR group (hazard ratio, 0.31; 95% CI, 0.15 to 0.67). At 3 years, 58.0% of the patients in the ibrutinib-venetoclax group had stopped therapy owing to undetectable MRD. After 5 years of ibrutinib-venetoclax therapy, 65.9% of the patients had undetectable MRD in the bone marrow and 92.7% had undetectable MRD in the peripheral blood. The risk of infection was similar in the ibrutinib-venetoclax group and the FCR group. The percentage of patients with cardiac serious adverse events was higher in the ibrutinib-venetoclax group than in the FCR group (10.7% vs. 0.4%). CONCLUSIONS: MRD-directed ibrutinib-venetoclax improved progression-free survival as compared with FCR, and results for overall survival also favored ibrutinib-venetoclax. (Funded by Cancer Research UK and others; FLAIR ISRCTN Registry number, ISRCTN01844152; EudraCT number, 2013-001944-76.).

Match Running Performance in Australian Football Is Related to Muscle Fiber Typology.

PURPOSE: To examine the association between muscle fiber typology and match running performance in professional Australian football (AF) athletes. METHODS: An observational time-motion analysis was performed on 23 professional AF athletes during 224 games throughout the 2020 competitive season. Athletes were categorized by position as hybrid, small, or tall. Athlete running performance was measured using Global Navigation Satellite System devices. Mean total match running performance and maximal mean intensity values were calculated for moving mean durations between 1 and 10 minutes for speed (in meters per minute), high-speed-running distance (HSR, >4.17 m·s-1), and acceleration (in meters per second squared), while intercept and slopes were calculated using power law. Carnosine content was quantified by proton magnetic resonance spectroscopy in the gastrocnemius and soleus and expressed as a carnosine aggregate z score (CAZ score) to estimate muscle fiber typology. Mixed linear models were used to determine the association between CAZ score and running performance. RESULTS: The mean (range) CAZ score was -0.60 (-1.89 to 1.25), indicating that most athletes possessed a greater estimated proportion of type I muscle fibers. A greater estimated proportion of type I fibers (ie, lower CAZ score) was associated with a larger accumulation of HSR (>4.17 m·s-1) and an increased ability to maintain HSR as the peak period duration increased. CONCLUSION: AF athletes with a greater estimated proportion of type I muscle fibers were associated with a greater capacity to accumulate distance running at high speeds, as well as a greater capacity to maintain higher output of HSR running during peak periods as duration increases.

Hamstring harvest results in significantly reduced knee muscular protection during side-step cutting two years after anterior cruciate ligament reconstruction.

The purpose of this study was to determine the effect of donor muscle morphology following tendon harvest in anterior cruciate ligament (ACL) reconstruction on muscular support of the tibiofemoral joint during sidestep cutting. Magnetic resonance imaging (MRI) was used to measure peak cross-sectional area (CSA) and volume of the semitendinosus (ST) and gracilis (GR) muscles and tendons (bilaterally) in 18 individuals following ACL reconstruction. Participants performed sidestep cutting tasks in a biomechanics laboratory during which lower-limb electromyography, ground reaction loads, whole-body motions were recorded. An EMG driven neuro-musculoskeletal model was subsequently used to determine force from 34 musculotendinous units of the lower limb and the contribution of the ST and GR to muscular support of the tibiofemoral joint based on a normal muscle-tendon model (Standard model). Then, differences in peak CSA and volume between the ipsilateral/contralateral ST and GR were used to adjust their muscle-tendon parameters in the model followed by a recalibration to determine muscle force for 34 musculotendinous units (Adjusted model). The combined contribution of the donor muscles to muscular support about the medial and lateral compartments were reduced by 52% and 42%, respectively, in the adjusted compared to standard model. While the semimembranosus (SM) increased its contribution to muscular stabilisation about the medial and lateral compartment by 23% and 30%, respectively. This computer simulation study demonstrated the muscles harvested for ACL reconstruction reduced their support of the tibiofemoral joint during sidestep cutting, while the SM may have the potential to partially offset these reductions. This suggests donor muscle impairment could be a factor that contributes to ipsilateral re-injury rates to the ACL following return to sport.

Ibrutinib and rituximab versus fludarabine, cyclophosphamide, and rituximab for patients with previously untreated chronic lymphocytic leukaemia (FLAIR): interim analysis of a multicentre, open-label, randomised, phase 3 trial.

BACKGROUND: The approval of Bruton tyrosine kinase (BTK) inhibitors in patients with previously untreated chronic lymphocytic leukaemia (CLL) was based on trials which compared ibrutinib with alkylating agents in patients considered unfit for fludarabine, cyclophosphamide, and rituximab, the most effective chemoimmunotherapy in CLL. We aimed to assess whether ibrutinib and rituximab is superior to fludarabine, cyclophosphamide, and rituximab in terms of progression-free survival. METHODS: This study is an interim analysis of FLAIR, which is an open-label, randomised, controlled, phase 3 trial in patients with previously untreated CLL done at 101 UK National Health Service hospitals. Eligible patients were between 18 and 75 years of age with a WHO performance status of 2 or less and disease status requiring treatment according to International Workshop on CLL criteria. Patients with greater than 20% of their CLL cells having the chromosome 17p deletion were excluded. Patients were randomly assigned (1:1) by means of minimisation (Binet stage, age, sex, and centre) with a random element in a web-based system to ibrutinib and rituximab (ibrutinib administered orally at 420 mg/day for up to 6 years; rituximab administered intravenously at 375 mg/m2 on day 1 of cycle 1 and at 500 mg/m2 on day 1 of cycles 2-6 of a 28-day cycle) or fludarabine, cyclophosphamide, and rituximab (fludarabine 24 mg/m2 per day orally on day 1-5, cyclophosphamide 150 mg/m2 per day orally on days 1-5; rituximab as above for up to 6 cycles). The primary endpoint was progression-free survival, analysed by intention to treat. Safety analysis was per protocol. This study is registered with ISRCTN, ISRCTN01844152, and EudraCT, 2013-001944-76, and recruiting is complete. FINDINGS: Between Sept 19, 2014, and July 19, 2018, of 1924 patients assessed for eligibility, 771 were randomly assigned with median age 62 years (IQR 56-67), 565 (73%) were male, 206 (27%) were female and 507 (66%) had a WHO performance status of 0. 385 patients were assigned to fludarabine, cyclophosphamide, and rituximab and 386 patients to ibrutinib and rituximab. After a median follow-up of 53 months (IQR 41-61) and at prespecified interim analysis, median progression-free survival was not reached (NR) with ibrutinib and rituximab and was 67 months (95% CI 63-NR) with fludarabine, cyclophosphamide, and rituximab (hazard ratio 0·44 [95% CI 0·32-0·60]; p<0·0001). The most common grade 3 or 4 adverse event was leukopenia (203 [54%] patients in the fludarabine, cyclophosphamide, and rituximab group and 55 [14%] patients in the ibrutinib and rituximab group. Serious adverse events were reported in 205 (53%) of 384 patients receiving ibrutinib and rituximab compared with 203 (54%) of 378 patients receiving fludarabine, cyclophosphamide, and rituximab. Two deaths in the fludarabine, cyclophosphamide, and rituximab group and three deaths in the ibrutinib and rituximab group were deemed to be probably related to treatment. There were eight sudden unexplained or cardiac deaths in the ibrutinib and rituximab group and two in the fludarabine, cyclophosphamide, and rituximab group. INTERPRETATION: Front line treatment with ibrutinib and rituximab significantly improved progression-free survival compared with fludarabine, cyclophosphamide, and rituximab but did not improve overall survival. A small number of sudden unexplained or cardiac deaths in the ibrutinib and rituximab group were observed largely among patients with existing hypertension or history of cardiac disorder. FUNDING: Cancer Research UK and Janssen.

Morphology of proximal and distal human semitendinosus compartments and the effects of distal tendon harvesting for anterior cruciate ligament reconstruction.

The human semitendinosus muscle is characterized by a tendinous inscription separating proximal and distal neuromuscular compartments. As each compartment is innervated by separate nerve branches, potential exists for independent operation and control of compartments. However, the morphology and function of each compartment have not been thoroughly examined in an adult human population. Further, the distal semitendinosus tendon is typically harvested for use in anterior cruciate ligament reconstruction surgery, which induces long-term morphological changes to the semitendinosus muscle-tendon unit. It remains unknown if muscle morphological alterations following anterior cruciate ligament reconstruction are uniform between proximal and distal semitendinosus compartments. Here, we performed magnetic resonance imaging on 10 individuals who had undergone anterior cruciate ligament reconstruction involving an ipsilateral distal semitendinosus tendon graft 14 ± 4 months prior, extracting morphological parameters of the whole semitendinosus muscle and each individual compartment from both the (non-injured) contralateral and surgical legs. In the contralateral leg, volume and length of the proximal compartment were smaller than the distal compartment. No between-compartment differences in volume or length were found for anterior cruciate ligament reconstructed legs, likely due to greater shortening of the distal compared to the proximal compartment after anterior cruciate ligament reconstruction. The maximal anatomical cross-sectional area of both compartments was substantially smaller on the anterior cruciate ligament reconstructed leg but did not differ between compartments on either leg. The absolute and relative between-leg differences in proximal compartment morphology on the anterior cruciate ligament reconstructed leg were strongly correlated with the corresponding between-leg differences in distal compartment morphological parameters. Specifically, greater between-leg morphological differences in one compartment were highly correlated with large between-leg differences in the other compartment, and vice versa for smaller differences. These relationships indicate that despite the heterogeneity in compartment length and volume, compartment atrophy is not independent or random. Further, the tendinous inscription endpoints were generally positioned at the same proximodistal level as the compartment maximal anatomical cross-sectional areas, providing a wide area over which the tendinous inscription could mechanically interact with compartments. Overall, results suggest the two human semitendinosus compartments are not mechanically independent.

Venetoclax ramp-up strategies for chronic lymphocytic leukaemia in the United Kingdom: a real world multicentre retrospective study.

This retrospective, observational study evaluated patterns of inpatient versus outpatient tumour lysis syndrome (TLS) monitoring during venetoclax ramp-up in 170 patients with chronic lymphocytic leukaemia. The primary outcome was clinical/biochemical TLS. Two clinical and four biochemical TLS occurred (4.1%). Five of the six events occurred in high-risk patients, four occurred at 20 mg dose and three at the 6-h time-point. Inpatient versus outpatient TLS rates within the high-risk subgroup were 15% and 8%. Risk category was the only predictor of TLS events in multivariate analysis. Outpatient escalation did not associate with clinically meaningful TLS events, suggesting outpatient escalation has manageable associated TLS risks, including in high-risk cohorts. These observations require confirmation in larger studies.

Reducing oral steroid intolerability and drug costs for acute wheezers: A retrospective evaluation of a clinical management algorithm in a Pediatric Emergency Department.

PROJECT AIM: To retrospectively evaluate a clinical management algorithm for acute wheezers in a UK Pediatric Emergency Department (PED). OVERVIEW AND RATIONALE: Acute wheezing attacks are a leading cause of PED attendances and inpatient admissions. Prednisolone, a routine treatment, is intolerable in almost one-third of children, requiring repeated dosing, which may prolong length of stay (LOS). To address this problem, we: (1) developed an acute management algorithm (concise, single-sided flow-chart, instructing immediate management); (2) modified the OCS regime from prednisolone (1 mg/kg, 3-day course) to dexamethasone (600 then 300 mcg/kg); (3) and disseminated guidance regionally. Written information-handouts, e-mails, and posters-were followed-up with verbal reinforcement. We implemented the algorithm in 2017 and revised it further in 2018. EVALUATION: In 2019, we retrospectively collected data on 100 acute wheeze attendances (those requiring OCS, aged 2-14), between October and December in 2016, 2017, and 2018 (n = 300), and assessed outcomes. RESULTS: Over a 48-month period, we reduced OCS intolerability by 67.2% and OCS drug costs by 85.8% (saving £41,470.14), while not significantly influencing the other outcomes. CONCLUSIONS: Reduced intolerability and substantial cost savings can be achieved by implementing a structured acute pediatric wheeze algorithm and modifying the OCS to single-dose dexamethasone (300 mcg/kg).

Damage amplification during repetitive seismic waves in mechanically loaded rocks.

Cycles of stress build-up and release are inherent to tectonically active planets. Such stress oscillations impart strain and damage, prompting mechanically loaded rocks and materials to fail. Here, we investigate, under uniaxial conditions, damage accumulation and weakening caused by time-dependent creep (at 60, 65, and 70% of the rocks' expected failure stress) and repeating stress oscillations (of ± 2.5, 5.0 or 7.5% of the creep load), simulating earthquakes at a shaking frequency of ~ 1.3 Hz in volcanic rocks. The results show that stress oscillations impart more damage than constant loads, occasionally prompting sample failure. The magnitudes of the creep stresses and stress oscillations correlate with the mechanical responses of our porphyritic andesites, implicating progressive microcracking as the cause of permanent inelastic strain. Microstructural investigation reveals longer fractures and higher fracture density in the post-experimental rock. We deconvolve the inelastic strain signal caused by creep deformation to quantify the amount of damage imparted by each individual oscillation event, showing that the magnitude of strain is generally largest with the first few oscillations; in instances where pre-existing damage and/or the oscillations' amplitude favour the coalescence of micro-cracks towards system scale failure, the strain signal recorded shows a sharp increase as the number of oscillations increases, regardless of the creep condition. We conclude that repetitive stress oscillations during earthquakes can amplify the amount of damage in otherwise mechanically loaded materials, thus accentuating their weakening, a process that may affect natural or engineered structures. We specifically discuss volcanic scenarios without wholesale failure, where stress oscillations may generate damage, which could, for example, alter pore fluid pathways, modify stress distribution and affect future vulnerability to rupture and associated hazards.

Obinutuzumab as consolidation after chemo-immunotherapy: Results of the UK National Cancer Research Institute phase II/III GALACTIC trial.

The GA101 (obinutuzumab) monocLonal Antibody as Consolidation Therapy In chronic lymphocytic leukaemia (CLL) (GALACTIC) was a seamless phase II/III trial designed to test whether consolidation with obinutuzumab is safe and eradicates minimal residual disease (MRD) and, subsequently, whether this leads to prolonged progression-free survival (PFS) in patients with CLL who have recently responded to chemo-immunotherapy. Patients with a response 3-24 months after chemotherapy were assessed for MRD. MRD-positive patients were randomised to receive consolidation therapy with obinutuzumab or no consolidation. The trial closed after the phase II part due to slow recruitment. In all, 48 patients enrolled of whom 19 were MRD negative and were monitored. Of the 29 MRD-positive patients, 14 were randomised to receive consolidation and 15 to no consolidation. At 6 months after randomisation, 10 and 13 consolidated patients achieved MRD negativity by flow cytometry (sensitivity 10-4 ) in bone marrow and peripheral blood respectively. PFS was significantly better in consolidated patients compared to non-consolidated patients (p = 0.001). No difference was observed in PFS, overall survival or duration of MRD negativity when comparing the 10 MRD-negative patients after consolidation with the 19 MRD-negative patients in the monitoring group. Common adverse events in the consolidation arm were thrombocytopenia, infection, and cough. Only 1% of events were infusion-related reactions. This observation provides further evidence that consolidation to achieve MRD negativity improves outcomes in CLL and that obinutuzumab is well tolerated in patients with low levels of disease.

The Muscle Typology of Elite and World-Class Swimmers.

PURPOSE: To examine whether the muscle typology of elite and world-class swimmers could discriminate between their best distance event, swimming stroke style, or performance level. METHODOLOGY: The muscle carnosine content of 43 male (860 [76] FINA [Fédération Internationale de Natation] points) and 30 female (881 [63] FINA points) swimmers was measured in the soleus and gastrocnemius by proton magnetic resonance spectroscopy and expressed as a carnosine aggregate Z score (CAZ score) to estimate muscle typology. A higher CAZ score is associated with a higher estimated proportion of type II fibers. Swimmers were categorized by their best stroke, distance category (sprinters, 50-100 m; middle distance, 200-400 m; or long distance, 800 m-open water), and performance level (world-class, world top 10, or elite and world top 100 swimmers outside of the world top 10). RESULTS: There was no significant difference in the CAZ score of sprint- (-0.08 [0.55]), middle- (-0.17 [0.70]), or long-distance swimmers (-0.30 [0.75], P = .693). World-class sprint swimmers (all strokes included) had a significantly higher CAZ score (0.37 [0.70]) when compared to elite sprint swimmers (-0.25 [0.61], P = .024, d = 0.94). Breaststroke swimmers (0.69 [0.73]) had a significantly higher CAZ score compared to freestyle (-0.24 [0.54], P < .001, d = 1.46), backstroke (-0.16 [0.47], P = .006, d = 1.42), and butterfly swimmers (-0.39 [0.53], P < .001, d = 1.70). Furthermore, within the cohort of breaststroke swimmers, there was a significant positive correlation between FINA points and CAZ score (r = .728, P = .011); however, this association was not evident in other strokes. CONCLUSION: While there was no clear association between muscle typology and event distance specialization, world-class sprint swimmers possess a greater estimated proportion of type II fibers compared to elite sprint swimmers, as well as breaststroke swimmers compared to freestyle, backstroke, and butterfly swimmers.

Dark-field tomography of an attenuating object using intrinsic x-ray speckle tracking.

Purpose: We investigate how an intrinsic speckle tracking approach to speckle-based x-ray imaging is used to extract an object's effective dark-field (DF) signal, which is capable of providing object information in three dimensions. Approach: The effective DF signal was extracted using a Fokker-Planck type formalism, which models the deformations of illuminating reference beam speckles due to both coherent and diffusive scatter from the sample. Here, we assumed that (a) small-angle scattering fans at the exit surface of the sample are rotationally symmetric and (b) the object has both attenuating and refractive properties. The associated inverse problem of extracting the effective DF signal was numerically stabilized using a "weighted determinants" approach. Results: Effective DF projection images, as well as the DF tomographic reconstructions of the wood sample, are presented. DF tomography was performed using a filtered back projection reconstruction algorithm. The DF tomographic reconstructions of the wood sample provided complementary, and otherwise inaccessible, information to augment the phase contrast reconstructions, which were also computed. Conclusions: An intrinsic speckle tracking approach to speckle-based imaging can tomographically reconstruct an object's DF signal at a low sample exposure and with a simple experimental setup. The obtained DF reconstructions have an image quality comparable to alternative x-ray DF techniques.

Free Achilles tendon strain during selected rehabilitation, locomotor, jumping, and landing tasks.

A better understanding of the strains experienced by the Achilles tendon during commonly prescribed exercises and locomotor tasks is needed to improve efficacy of Achilles tendon training and rehabilitation programs. The aim of this study was to estimate in vivo free Achilles tendon strain during selected rehabilitation, locomotor, jumping, and landing tasks. Sixteen trained runners with no symptoms of Achilles tendinopathy participated in this study. Personalized free Achilles tendon moment arm and force-strain curve were obtained from imaging data and used in conjunction with motion capture and surface electromyography to estimate free Achilles tendon strain using electromyogram-informed neuromusculoskeletal modeling. There was a strong correspondence between Achilles tendon force estimates from the present study and experimental data reported in the literature (R2 > 0.85). The average tendon strain was highest for maximal hop landing (8.8 ± 1.6%), lowest for walking at 1.4 m/s (3.1 ± 0.8%), and increased with locomotor speed during running (run 3.0 m/s: 6.5 ± 1.6%; run 5.0 m/s: 7.9 ± 1.7%) and during heel rise exercise with added mass (BW: 5.8 ± 1.3%; 1.2 BW: 6.9 ± 1.7%). The peak tendon strain was highest during running (5 m/s: 13.7 ± 2.5%) and lowest during walking (1.4 m/s: 7 ± 1.8%). Overall findings provide a preliminary evidence base for exercise selection to maximize anabolic tendon remodeling during training and rehabilitation of the Achilles tendon.NEW & NOTEWORTHY Our work combines medical imaging and electromyogram-informed neuromusculoskeletal modeling data to estimate free Achilles tendon strain during selected rehabilitation, locomotor, jumping, and landing tasks in trained middle-distance runners. These data may potentially be used to inform Achilles tendon training and rehabilitation to maximize anabolic tendon remodeling.

Determinants of Performance in Paced and Maximal 800-m Running Time Trials.

PURPOSE: We aimed to identify the underpinning physiological and speed/mechanical determinants of different types of 800-m running time trials (i.e., with a positive or negative pacing strategy) and key components within each 800-m time trial (i.e., first and final 200 m). METHODS: Twenty trained male 800-m runners (800-m personal best time (min:s): 1:55.10 ± 0:04.44) completed a maximal 800-m time trial (800MAX) and one pacing trial, whereby runners were paced for the first lap, and speed was reduced by 7.5% (800PACE) relative to 800MAX, whereas the last lap was completed in the fastest time possible. Anaerobic speed reserve, running economy, the velocity corresponding with V˙O2peak (VV˙O2peak), maximal sprint speed (MAXSS), maximal accumulated oxygen deficit, and sprint force-velocity-power profiles were derived from laboratory and field testing. Carnosine content was quantified by proton magnetic resonance spectroscopy in the gastrocnemius and soleus and expressed as a carnosine aggregate Z (CAZ) score to estimate muscle typology. Data were analyzed using multiple stepwise regression analysis. RESULTS: MAXSS and vV˙O2peak largely explained the variation in 800MAX time (r2 = 0.570; P = 0.020), whereas MAXSS was the best explanatory variable for the first 200-m time in 800MAX (adjusted r2 = 0.661, P < 0.001). Runners with a higher CAZ score (i.e., higher estimated percentage of type II fibers) reduced their last lap time to a greater extent in 800PACE relative to 800MAX (adjusted r2 = 0.413, P < 0.001), whereas better maintenance of mechanical effectiveness during sprinting, a higher CAZ score and vV˙O2peak was associated with a faster final 200-m time during 800PACE (adjusted r2 = 0.761, P = 0.001). CONCLUSIONS: These findings highlight that diversity in the physiological and speed/mechanical characteristics of male middle-distance runners may be associated with their suitability for different 800-m racing strategies to have the best chance of winning.

The Influence of Muscle Fiber Typology on the Pacing Strategy of 200-m Freestyle Swimmers.

PURPOSE: To determine the influence of muscle fiber typology (MFT) on the pacing strategy of elite swimmers competing in the 200-m freestyle event. METHOD: The top 3 career-best performances from 25 elite 200-m freestyle swimmers were analyzed-12 women (1:58.0 [0:01.3] min:s) and 13 men (1:48.4 [0:02.5]). Muscle carnosine concentration was quantified by proton magnetic resonance spectroscopy in the gastrocnemius and soleus muscles and expressed as a carnosine aggregate z score (CAZ score) relative to an age- and gender-matched nonathlete control group to estimate MFT. Linear regression models were employed to examine the influence of MFT on the percentage of overall race time spent in each 50-m lap. RESULTS: Swimmers with a higher CAZ score spent a greater percentage of race time in lap 3 compared with swimmers with a lower CAZ score (0.1%, 0.0% to 0.2%; mean, 90% confidence interval, P = .02). For every 1% increase in the percentage of race time spent in lap 1, the percentage of race time spent in lap 3 decreased by 0.4% for swimmers with a higher CAZ score (0.2% to -0.5%, P = .00, r = -.51), but not for swimmers with a lower CAZ score (-0.1%, -0.3% to 0.1%, P = .28, r = -.18). The percentage of race time spent in lap 4 decreased by 0.8% for higher-CAZ-score swimmers (-0.5% to -1.0%, P = .00, r = -.66) and by 0.9% for lower-CAZ-score swimmers (-0.6% to -1.3%, P = .00, r = -.65) when lap 1 percentage increased by 1%. CONCLUSION: MFT may influence the pacing strategy of swimmers in the 200-m freestyle event, which provides an avenue for maximizing individualized pacing strategies of elite swimmers.

Muscle Fiber Typology and Its Association With Start and Turn Performance in Elite Swimmers.

PURPOSE: To determine the association between estimated muscle fiber typology and the start and turn phases of elite swimmers during competition. METHODS: International and national competition racing performance was analyzed from 21 female (FINA points = 894 ± 39: 104.5 ± 1.8% world record ratio [WRR]) and 25 male (FINA points = 885 ± 54: 104.8 ± 2.1% WRR) elite swimmers. The start, turn, and turn out times were determined from each of the swimmers' career best performance times (FINA points = 889 ± 48: 104.7 ± 2.0% WRR). Muscle carnosine concentration was quantified by proton magnetic resonance spectroscopy in the gastrocnemius and soleus and was expressed as a carnosine aggregate z score relative to an age- and gender-matched nonathlete control group to estimate muscle fiber typology. Linear mixed models were employed to determine the association between muscle fiber typology and the start and turn times. RESULTS: While there was no significant influence of carnosine aggregate z score on the start and turn times when all strokes and distance events were entered into the model, the swimmers with a higher carnosine aggregate z score (ie, faster muscle typology) had a significantly faster start time in 100-m events compared with the swimmers with a lower carnosine aggregate z score (P = .02, F = 5.825). The start and turn times were significantly faster in the male compared with the female swimmers in the 100-m events compared with other distances, and between the 4 different swimming strokes (P < .001). CONCLUSION: This study suggests that start times in sprint events are partly determined (and limited) by muscle fiber typology, which is highly relevant when ∼12% of the overall performance time is determined from the start time.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroconversion in hematology-oncology patients.

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China at the end of 2019, the virus has spread rapidly across the globe leading to millions of infections and subsequent deaths. Although the virus infects those exposed indiscriminately, there are groups in society at an increased risk of severe infection, leading to increased morbidity. Patients suffering from hematological cancers, particularly leukemia, lymphoma, and myeloma, may be one such group and previous studies have suggested that they may be at a three to four times greater risk of severe COVID-19 after SARS-CoV-2 infection, leading to admissions to ICU, mechanical ventilation, and death compared to those without such malignancies. Serological testing for IgG seroconversion has been extensively studied in the immunocompetent, but fewer publications have characterized this process in large series of immunocompromised patients. This study described 20 patients with hematological cancers who tested positive for SARS-CoV-2 via PCR with 12 of the patients receiving further serological testing. We found that of the 12 patients screened for SARS-CoV-2 IgG antibodies, only 2 (16.6%) were able to generate an immune response to the infection. Yet despite this low seroconversion rate in this cohort, none of these patients died or became particularly unwell with COVID-19 or its related complications.

A review framework of how earthquakes trigger volcanic eruptions.

It is generally accepted that tectonic earthquakes may trigger volcanic activity, although the underlying mechanisms are poorly constrained. Here, we review current knowledge, and introduce a novel framework to help characterize earthquake-triggering processes. This framework outlines three parameters observable at volcanoes, namely magma viscosity, open- or closed-system degassing and the presence or absence of an active hydrothermal system. Our classification illustrates that most types of volcanoes may be seismically-triggered, though require different combinations of volcanic and seismic conditions, and triggering is unlikely unless the system is primed for eruption. Seismically-triggered unrest is more common, and particularly associated with hydrothermal systems.

Relationships between Lower Limb Muscle Characteristics and Force-Velocity Profiles Derived during Sprinting and Jumping.

PURPOSE: This study aimed to identify the relationships between lower limb muscle characteristics and mechanical variables derived from the vertical (jumping) and horizontal (sprinting) force-velocity-power (FVP) profiles. METHODS: Nineteen subelite male rugby league players performed a series of squat jumps and linear 30-m sprints to derive the vertical and horizontal FVP profiles, respectively. The theoretical maximal force (F0), velocity (V0), and power (Pmax) were derived from both the vertical (i.e., vF0, vV0, and vPmax) and the horizontal (i.e., hF0, hV0, and hPmax) FVP profiles. Vastus lateralis (VL), biceps femoris long head, and gastrocnemius medialis (GM) and lateralis muscle fascicle length, pennation angle, and thickness were measured using B-mode ultrasonography. Magnetic resonance imaging was used to calculate volumes of major lower limb muscles, whereas proton magnetic resonance spectroscopy was used to quantify the carnosine content of the GM to estimate muscle fiber typology. RESULTS: Variation in vPmax was best explained by GM muscle fiber typology (i.e., greater estimated proportion of Type II fibers) and VL volume (adjusted r2 = 0.440, P = 0.006), whereas adductor and vastus medialis volume and GM muscle fiber typology explained the most variation in hPmax (adjusted r2 = 0.634, P = 0.032). Rectus femoris and VL volume explained variation in vF0 (r2 = 0.430, P = 0.008), whereas adductor and vastus medialis volume explained variation in hF0 (r2 = 0.432, P = 0.007). Variations in vV0 and hV0 were best explained by GM muscle fiber typology (adjusted r2 = 0.580, P < 0.001) and GM muscle fiber typology and biceps femoris short head volume (adjusted r2 = 0.590, P < 0.001), respectively. CONCLUSION: Muscle fiber typology and muscle volume are strong determinants of maximal muscle power in jumping and sprinting by influencing the velocity- and force-oriented mechanical variables.

Determinants of last lap speed in paced and maximal 1500-m time trials.

PURPOSE: The present study identified the physiological and performance characteristics that are deterministic during a maximal 1500-m time trial and in paced 1500-m time trials, with an all-out last lap. METHODS: Thirty-two trained middle-distance runners (n = 21 male, VO2peak: 72.1 ± 3.2; n = 11, female, VO2peak: 61.2 ± 3.7 mL kg-1 min-1) completed a 1500-m time trial in the fastest time possible (1500FAST) as well as a 1500MOD and 1500SLOW trial whereby mean speed was reduced during the 0-1100 m by 5% and 10%, respectively. Anaerobic speed reserve (ASR), running economy (RE), the velocity corresponding with VO2peak (VVO2peak), maximal sprint speed (MSS) and maximal accumulated oxygen deficit (MAOD) were determined during additional testing. Carnosine content was quantified by proton magnetic resonance spectroscopy in the gastrocnemius and expressed as a Z-score to estimate muscle fibre typology. RESULTS: 1500FAST time was best explained by RE and VVO2peak in female runners (adjusted r2 = 0.80, P < 0.001), in addition to the 0-1100-m speed relative to VVO2peak in male runners (adjusted r2 = 0.72, P < 0.001). Runners with a higher gastrocnemius carnosine Z-score (i.e., higher estimated percentage of type II fibres) and greater MAOD, reduced their last lap time to a greater extent in the paced 1500-m trials. Neither ASR nor MSS was associated with last lap time in the paced trials. CONCLUSION: These findings suggest that VVO2 peak and RE are key determinants of 1500-m running performance with a sustained pace from the start, while a higher carnosine Z-score and MAOD are more important for last lap speed in tactical 1500-m races.