The multi-specific VH-based Humabody CB213 co-targets PD1 and LAG3 on T cells to promote anti-tumour activity.

BACKGROUND: Improving cancer immunotherapy long-term clinical benefit is a major priority. It has become apparent that multiple axes of immune suppression restrain the capacity of T cells to provide anti-tumour activity including signalling through PD1/PD-L1 and LAG3/MHC-II. METHODS: CB213 has been developed as a fully human PD1/LAG3 co-targeting multi-specific Humabody composed of linked VH domains that avidly bind and block PD1 and LAG3 on dual-positive T cells. We present the preclinical primary pharmacology of CB213: biochemistry, cell-based function vs. immune-suppressive targets, induction of T cell proliferation ex vivo using blood obtained from NSCLC patients, and syngeneic mouse model anti-tumour activity. CB213 pharmacokinetics was assessed in cynomolgus macaques. RESULTS: CB213 shows picomolar avidity when simultaneously engaging PD1 and LAG3. Assessing LAG3/MHC-II or PD1/PD-L1 suppression individually, CB213 preferentially counters the LAG3 axis. CB213 showed superior activity vs. αPD1 antibody to induce ex vivo NSCLC patient T cell proliferation and to suppress tumour growth in a syngeneic mouse tumour model, for which both experimental systems possess PD1 and LAG3 suppressive components. Non-human primate PK of CB213 suggests weekly clinical administration. CONCLUSIONS: CB213 is poised to enter clinical development and, through intercepting both PD1 and LAG3 resistance mechanisms, may benefit patients with tumours escaping front-line immunological control.

The dose-response relationship between interval-training and VO2max in well-trained endurance runners: A systematic review.

Success in endurance running is primarily determined by maximal aerobic power (VO2max), fractional utilization, and running economy (RE). Within the literature, two training modalities have been identified to improve VO2max; continuous training (CT) and interval-training (IT). The efficacy of IT to improve VO2max in well-trained runners remains equivocal, as does whether a dose-response relationship exists between the IT training load performed and changes in VO2max. A keyword search was performed in five electronic databases. Seven studies met the inclusion criteria for this systematic review. The training impulse (TRIMP) was calculated to analyse relationships between training load and changes in VO2max, by calculating the time accumulated in certain intensity domains throughout a training intervention. Non-significant (P>0.05) improvements in VO2max were reported in six studies, with only one study reporting a significant (P<0.05) improvement following the IT interventions. A relationship between the training session impulse of the interval-training performed (IT STRIMP) and VO2max improvements were observed. The efficacy of IT to improve VO2max in well-trained runners remains equivocal, nevertheless, the novel method of training-load analysis demonstrates a relationship between the IT STRIMP and VO2max improvements. This provides practical application for the periodization of IT within the training regime of well-trained distance runners.

Inter-limb strength asymmetry in adolescent distance runners: Test-retest reliability and relationships with performance and running economy.

The purpose of this investigation was, firstly, to quantify the test-retest reliability of strength measures in adolescent distance runners; and secondly, to explore the relationships between inter-limb strength asymmetry and performance and running economy (RE) in a similar cohort of young runners. For the reliability study, twelve (n = 6 female) post-pubertal adolescent distance runners performed an isometric quarter-squat on a dual force plate and unilateral isometric hip extension and hip abduction tests on two occasions. For the correlation study, participants (n = 31) performed the strength tests plus a submaximal incremental running assessment and a maximal running test. Running economy was expressed as the average energy cost of running for all speeds below lactate turnpoint and was scaled for body mass using a previously calculated power exponent. Allometrically scaled peak force during the quarter-squat and peak torque in the hip strength tasks showed acceptable levels of reproducibility (typical error ≤6.3%). Relationships between strength asymmetry and performance and RE were low or negligible (r < 0.47, p > 0.05), except for hip abduction strength asymmetry and RE in the female participants (r = 0.85, p < 0.001, n = 16). Practitioners should consider inter-limb hip abduction strength asymmetry on an individual level, and attempting to reduce this asymmetry in females may positively impact RE.

The Reliability of Potential Fatigue-Monitoring Measures in Elite Youth Soccer Players.

ABSTRACT: Fitzpatrick, JF, Hicks, KM, Russell, M, and Hayes, PR. The reliability of potential fatigue-monitoring measures in elite youth soccer players. J Strength Cond Res 35(12): 3448-3452, 2021-Monitoring fatigue is of vital importance to practitioners; however, logistics and concerns about reliability may impede the use of certain measures. This study aimed to quantify the reliability of potential measures of fatigue; a subjective wellness questionnaire, jump performance tests, and tri-axial accelerometer variables derived during submaximal shuttle running in elite youth soccer players. A secondary aim was to establish the minimum test duration that could be used for the submaximal shuttle run while maintaining good reliability. Seventeen male youth team players (age: 17.4 ± 0.5 years) were assessed on 2 occasions, spaced 7 days apart. Typical error, coefficient of variation (CV%), interclass correlation (ICC), and minimum detectable change were calculated for a subjective wellness questionnaire, countermovement jump (CMJ), squat jump (SJ) and drop jump contact time (DJ-CT), drop jump height (DJ-JH), and reactive strength (DJ-RSI). A novel submaximal shuttle running test was also used to assess tri-axial accelerometer data reliability. Results suggest that CMJ, SJ, DJ-CT, and DJ-RSI have good test-retest reliability (CV% = 4.5-7.7; ICC = 0.80-0.88); however DJ-JH did not show acceptable reliability (CV% = 6.0; ICC = 0.76). Good reliability was found for all tri-axial accelerometer variables during a 3-minute (2-minute analysis) submaximal shuttle run (CV% = 2.4-8.0; ICC = 0.81-0.95), except for % PlayerLoad anterior-posterior (%PLAP) (CV% = 7.2; ICC = 0.63). The subjective wellness questionnaire demonstrated poor reliability for all items (CV% = 11.2-30.0; ICC = 0.00-0.78). The findings from this study provide practitioners with valuable information about the reliability of a range of potential fatigue-monitoring measures. This can be used to help make accurate decisions about the magnitude of change in these assessments when used in practice.

Strength and Conditioning Habits of Competitive Distance Runners.

Blagrove, RC, Brown, N, Howatson, G, and Hayes, PR. Strength and conditioning habits of competitive distance runners. J Strength Cond Res 34(5): 1392-1399, 2020-Targeted strength and conditioning (S&C) programs can potentially improve performance and reduce injury risk factors in competitive runners. However, S&C practices of distance runners are unknown. This study aimed to explore S&C practices of competitive middle- and long-distance runners and examined whether reported frequency of injuries was influenced by training behaviors. One thousand eight hundred eighty-three distance runners (≥15 years old) completed an online survey. All runners who raced competitively were included in data analysis (n = 667). Distance runners mainly engaged with S&C activities to lower risk of injury (63.1%) and improve performance (53.8%). The most common activities used were stretching (86.2%) and core stability exercises (70.2%). Resistance training (RT) and plyometric training (PT) were used by 62.5 and 35.1% of runners, respectively. Junior (under-20) runners include PT, running drills, and circuit training more so than masters runners. Significantly more international standard runners engaged in RT, PT, and fundamental movement skills training compared with competitive club runners. Middle-distance (800-3,000 m) specialists were more likely to include RT, PT, running drills, circuit training, and barefoot exercises in their program than longer-distance runners. Injury frequency was associated with typical weekly running volume and run frequency. Strength and conditioning did not seem to confer a protection against the number of injuries the runners experienced. Practitioners working with distance runners should critically evaluate the current S&C practices of their athletes, to ensure that activities prescribed have a sound evidence-based rationale.

Quantification of aerobic determinants of performance in post-pubertal adolescent middle-distance runners.

PURPOSE: The use of oxygen cost ([Formula: see text]aero) parameters to predict endurance performance has recently been criticized. Instead, it is suggested that aerobic energy cost ([Formula: see text]) provides greater validity; however, a comparison of these quantification methods has not previously been made. METHODS: Fifty-six male (n = 34) and female (n = 22) competitive adolescent (17 ± 1 years) middle-distance runners participated in a sub-maximal and maximal incremental treadmill test. Running economy (RE) was measured at the speed corresponding to lactate turnpoint, and the three speeds prior. Maximal oxygen uptake ([Formula: see text]O2max), speed at [Formula: see text]O2max and fraction of [Formula: see text]O2max utilized across a range of intensities, and speeds from 0.8, 1.5 and 3 km races were also quantified. RE and fractional utilization were calculated in units of [Formula: see text]aero and [Formula: see text]aero. RESULTS: Multiple linear regression models demonstrated no discernible difference in the predictive capability of RE, fractional utilization and [Formula: see text]O2max when expressed as [Formula: see text]aero or [Formula: see text]aero in both sexes. When plotted as a function of running speed, [Formula: see text]aero displayed a stepwise decrease (F = 11.59, p < 0.001) whereas [Formula: see text]aero exhibited a curvilinear response (F = 4.74, p = 0.015). Differences were also evident in the slopes plotted for %[Formula: see text]O2max and %[Formula: see text]aeromax against running speed (F = 5.38, p = 0.021). CONCLUSIONS: Quantifying aerobic determinants of performance in units of [Formula: see text]aero provides no greater validity compared to [Formula: see text]aero-based measurement. Although both [Formula: see text]aero and [Formula: see text]aero are sensitive to changes in speed, [Formula: see text]aero provides the more valid reflection of the underlying metabolic cost of running. Physiologists should also be aware of the potential differences between expression of aerobic running intensity based upon %[Formula: see text]O2max compared to %[Formula: see text]aeromax.

Use of Loaded Conditioning Activities to Potentiate Middle- and Long-Distance Performance: A Narrative Review and Practical Applications.

Blagrove, RC, Howatson, G, and Hayes, PR. Use of loaded conditioning activities to potentiate middle- and long-distance performance: a narrative review and practical applications. J Strength Cond Res 33(8): 2288-2297, 2019-The warm-up is an integral component of a middle- and long-distance athlete's preperformance routine. The use of a loaded conditioning activity (LCA), which elicits a postactivation potentiation (PAP) response to acutely enhance explosive power performance, is well researched. A similar approach incorporated into the warm-up of a middle- or long-distance athlete potentially provides a novel strategy to augment performance. Mechanisms that underpin a PAP response, relating to acute adjustments within the neuromuscular system, should theoretically improve middle- and long-distance performance through improvements in submaximal force-generating ability. Attempts to enhance middle- and long-distance-related outcomes using an LCA have been used in several recent studies. Results suggest that benefits to performance may exist in well-trained middle- and long-distance athletes by including high-intensity resistance training (1-5 repetition maximum) or adding load to the sport skill itself during the latter part of warm-ups. Early stages of performance seem to benefit most, and it is likely that recovery (5-10 minutes) also plays an important role after an LCA. Future research should consider how priming activity, designed to enhance the VO2 kinetic response, and an LCA may interact to affect performance, and how different LCAs might benefit various modes and durations of middle- and long-distance exercises.

Excelling at youth level in competitive track and field athletics is not a prerequisite for later success.

Enhancing our understanding of athlete development would be valuable for coaches, parents and administrators to set realistic performance expectations and to advance youth sport policy. To this end, a database of track and field performances was examined. Records of 134,313 performances by athletes aged between 12 and 35 years in sprinting, throwing, jumping and middle distance events were analysed. Results revealed that a minority (Male, 9%; Female, 13%) of top 20 ranked senior athletes were also ranked in the top 20 at Under 13 (U13). These results were supported by the finding that a minority of athletes retained their top 20 ranking at subsequent age grades (36.3% U13-U15; 23% U13-U17; 13% U13-U20; 43.3% U15-U17; 22.1% U15-U20; 41.8% U17-U20). By U20, less than 30% of athletes who had been ranked in the top 20 at U13 were still listed on the national rankings. Examining a broader sample of athletes revealed weak to moderate correlations between performances at different age grades until at least Under 17-Under 20. These findings reinforce the message that excelling at youth level in competitive athletics is not a prerequisite for senior success.

Faster, higher, stronger, older: Relative age effects are most influential during the youngest age grade of track and field athletics in the United Kingdom.

The relative age effect (RAE) is a common phenomenon in youth sport, whereby children born early in the selection year are more likely to experience success and to sustain participation. There is a lack of research investigating variables which influence RAEs within track and field athletics. Such information is vital to guide policies in relation to competition structure, youth development squads and coach education. A database of competition results was analysed to determine the extent to which RAEs were present in track and field athletics in the United Kingdom. Subsequent analyses examined whether age, sex, event and skill level influenced the RAE. Examination of 77,571 records revealed that RAEs were widespread, but most pronounced during Under 13 (U13) competitions; that is, during athletes' first exposure to formal track and field competition. Sex, event and skill level further influenced the existence and magnitude of RAEs at different age grades. Relative age is a key influencing factor within track and field athletics, especially at the youngest age category. Consequently, national governing bodies need to consider what administrative and stakeholder initiatives are necessary to minimise the effects of RAEs on young athletes' early experiences of competition.

A 6-minute sub-maximal run test to predict VO2 max.

Maximal oxygen uptake ([Formula: see text] max) is a key indicator to assess health as well as sports performance. Currently, maximal exercise testing is the most accurate measure of maximal aerobic power, since submaximal approaches are still imprecise. In this paper, we propose a new method to predict [Formula: see text] max from a submaximal, low intensity, test in sports men and women. 182 males and 108 females from the High Performance Center of Pontevedra (Spain), aged 10-46 years old, with a [Formula: see text] max between 30.1 and 81.2 mL·min-1·kg-1, completed a maximal incremental test to volitional exhaustion. The test began at a speed of 6 km·h-1 and increased by 0.25 km·h-1 every 15 seconds. Using the data gathered during the first 6 minutes of the test, two different regression models were adjusted using functional data analysis and a traditional linear regression model with scalar covariates. The functional regression model obtained the best results, adjusted r2 = 0.845 and RMSE = 2.8 mL·min-1·kg-1, but the linear regression model also obtained a good fit, adjusted r2 = 0.798 and RMSE = 3.5 mL·min-1·kg-1. Both methods are more accurate than classical submaximal tests, although oxygen consumption needs to be measured during the test.

Effect of volume of milk consumed on the attenuation of exercise-induced muscle damage.

Exercise-induced muscle damage (EIMD) leads to decrements in muscle performance, increases in intramuscular proteins and delayed-onset of muscle soreness (DOMS). Previous research demonstrated that one litre of milk-based protein-carbohydrate (CHO) consumed immediately following muscle damaging exercise can limit changes in markers of EIMD possibly due to attenuating protein degradation and/or increasing protein synthesis. If the attenuation of EIMD is derived from changes in protein metabolism then it can be hypothesised that consuming a smaller volume of CHO and protein will elicit similar effects. Three independent matched groups of 8 males consumed 500 mL of milk, 1,000 mL of milk or a placebo immediately following muscle damaging exercise. Passive and active DOMS, isokinetic muscle performance, creatine kinase (CK), myoglobin and interleukin-6 were assessed immediately before and 24, 48 and 72 h after EIMD. After 72 h 1,000 mL of milk had a likely benefit for limiting decrements in peak torque compared to the placebo. After 48 h, 1,000 mL of milk had a very likely benefit of limiting increases in CK in comparison to the placebo. There were no differences between consuming 500 or 1,000 mL of milk for changes in peak torque and CK. In conclusion, decrements in isokinetic muscle performance and increases in CK can be limited with the consumption of 500 mL of milk.

Gait and Neuromuscular Changes Are Evident in Some Masters Club Level Runners 24-h After Interval Training Run.

Purpose: To examine the time course of recovery for gait and neuromuscular function immediately after and 24-h post interval training. In addition, this study compared the impact of different statistical approaches on detecting changes. Methods: Twenty (10F, 10M) healthy, recreational club runners performed a high-intensity interval training (HIIT) session consisting of six repetitions of 800 m. A 6-min medium intensity run was performed pre, post, and 24-h post HIIT to assess hip and knee kinematics and coordination variability. Voluntary activation and twitch force of the quadriceps, along with maximum isometric force were examined pre, post, and 24-h post significance HIIT. The time course of changes were examined using two different statistical approaches: traditional null hypothesis significance tests and "real" changes using minimum detectable change. Results: Immediately following the run, there were significant (P < 0.05) increases in the hip frontal kinematics and coordination variability. The runners also experienced a loss of muscular strength and neuromuscular function immediately post HIIT (P < 0.05). Individual assessment, however, showed that not all runners experienced fatigue effects immediately post HIIT. Null hypothesis significance testing revealed a lack of recovery in hip frontal kinematics, coordination variability, muscle strength, and neuromuscular function at 24-h post, however, the use of minimum detectable change suggested that most runners had recovered. Conclusion: High intensity interval training resulted in altered running kinematics along with central and peripheral decrements in neuromuscular function. Most runners had recovered within 24-h, although a minority still exhibited signs of fatigue. The runners that were not able to recover prior to their run at 24-h were identified to be at an increased risk of running-related injury.

Sirt1 overexpression in neurons promotes neurite outgrowth and cell survival through inhibition of the mTOR signaling.

The mammalian nicotinamide-adenine dinucleotide (NAD)-dependent deacetylase Sirt1 impacts different processes involved in the maintenance of brain integrity and in the pathogenic pathways associated with several neurodegenerative disorders, including Alzheimer's disease. Here we used human Sirt1 transgenic mice to demonstrate that neuron-specific Sirt1 overexpression promoted neurite outgrowth and improved cell viability under normal and nutrient-limiting conditions in primary culture systems and that Sirt1-overexpressing neurons exhibited higher tolerance to cell death or degeneration induced by amyloid-ß1-42 oligomers. Coincidentally, we found that enhanced Sirt1 expression in neurons downregulated the mammalian target of rapamycin (mTOR) protein levels and its phosphorylation without changes in its mRNA levels, which was accompanied by concomitant inhibition of the mTOR downstream signaling activity as revealed by decreased p70S6 kinase (p70S6K) phosphorylation at Thr389. Consistently with this, using a Sirt1 siRNA transfection approach, we observed that reduction of endogenous mouse Sirt1 led to increased levels of mTOR and phosphorylation of itself and p70S6K as well as impaired cell survival and neurite outgrowth in wild-type mouse primary neurons, corroborating a suppressing effect of mTOR by Sirt1. Correspondingly, the mTOR inhibitor rapamycin markedly improved neuronal cell survival in response to nutrient deprivation and significantly enhanced neurite outgrowth in wild-type mouse neurons. The protective effect of rapamycin was extended to neurons even with Sirt1 siRNA knockdown that displayed developmental abnormalities compared with siRNA control-treated cells. Collectively, our findings suggest that Sirt1 may act to promote growth and survival of neurons in the central nervous system via its negative modulation of mTOR signaling.

Depot- and ethnic-specific differences in the relationship between adipose tissue inflammation and insulin sensitivity.

OBJECTIVE: It is unclear whether there are differences in inflammatory gene expression between abdominal and gluteal subcutaneous adipose tissue (SAT), and between black and white women. We therefore tested the hypotheses that SAT inflammatory gene expression is greater in the abdominal compared to the gluteal depot, and SAT inflammatory gene expression is associated with differential insulin sensitivity (S(I) ) in black and white women. DESIGN AND METHODS: S(I) (frequently sampled intravenous glucose tolerance test) and abdominal SAT and gluteal SAT gene expression levels of 13 inflammatory genes were measured in normal-weight (BMI 18-25 kg/m²) and obese (BMI >30 kg/m²) black (n = 30) and white (n = 26) South African women. RESULTS: Black women had higher abdominal and gluteal SAT expression of CCL2, CD68, TNF-α and CSF-1 compared to white women (P < 0·01). Multivariate analysis showed that inflammatory gene expression in the white women explained 56·8% of the variance in S(I) (P < 0·005), compared to 20·9% in black women (P = 0·30). Gluteal SAT had lower expression of adiponectin, but higher expression of inflammatory cytokines, macrophage markers and leptin than abdominal SAT depots (P < 0·05). CONCLUSIONS: Black South African women had higher inflammatory gene expression levels than white women; however, the relationship between AT inflammation and S(I) was stronger in white compared to black women. Further research is required to explore other factors affecting S(I) in black populations. Contrary to our original hypothesis, gluteal SAT had a greater inflammatory gene expression profile than abdominal SAT depots. The protective nature of gluteo-femoral fat therefore requires further investigation.

The effect of muscular endurance on running economy.

The purpose of this study was to examine the relationship between fatigue-induced changes in running economy (RE) and muscular strength endurance (MSE). Ten well-trained male runners completed 2 runs of the same energy expenditure at 20%Δ VO(2) below LT. In the middle of the experimental condition (high intensity exercise [HIE]), there was a 4-minute block at sVO(2)max. The aim of the 4-minute block was to increase RE through fatigue, without inducing exhaustion. The MSE of hip extensors (HEs) and knee flexors (KFs) was assessed by 2 20-second eccentric bouts on an isokinetic dynamometer at 180°·s(-1). The RE increased after HIE compared to the control condition. Partial correlations found the increase in RE was strongly related with KF MSE (r = -0.709-0.798; p = 0.03-0.01). Greater MSE appeared to confer a fatigue resistant effect, resulting in a smaller increase in RE. The underlying mechanism of the fatigue resistant effect remains to be elucidated. Conditioning work focusing on augmenting eccentric muscular endurance of the legs may offer beneficial adaptations that promote fatigue resistance.

The Prevalence and Consequences of Within-Sport Specialization in Track and Field Athletics.

Purpose: The aim of this study was to provide an in-depth analysis of the prevalence and consequences of within-sport specialization in track and field in the United Kingdom. Method: The competition histories of top 100 ranked athletes from four representative events (100 m, 800 m, long jump, and shot put) were recorded from a publically-accessible database. Athletes were drawn from Under 20 (U20), U15, and U13 populations from the 2014/15 season, U15 populations from the 2009/10 season, and U13 populations from the 2007/08 season. Athletes' specialization status was defined based upon the number of event groups (sprint, endurance, jump, throw) in which they had recorded at least one performance. Chi-squared tests were used to examine the association between level of specialization at U13 and U15 and both performance and retention at subsequent age grades. Results: Within-sport specialization was rare among U13 and U15 track and field athletes, with approximately 10% of top 100 ranked U13s and 25% of top 100 ranked U15s competing in a single event group only. However, less than 35% of participants competed in sprinting, endurance running, jumping, and throwing events (i.e., diversification). There were no sex differences in the extent of specialization. Top ranked U20 female athletes were more likely to have diversified at U13 than their peers. There was no association between specialization at U13/U15 and subsequent retention. Conclusion: Administrators and coach educators should provide more sophisticated guidance for coaches and parents in relation to within-sport specialization.

Fatigue Induced Changes in Muscle Strength and Gait Following Two Different Intensity, Energy Expenditure Matched Runs.

PURPOSE: To investigate changes in hip and knee strength, kinematics, and running variability following two energy expenditure matched training runs; a medium intensity continuous run (MICR) and a high intensity interval training session (HIIT). METHODS: Twenty (10 Females, 10 Males) healthy master class runners were recruited. Each participant completed the HIIT consisting of six repetitions of 800 m with a 1:1 work: rest ratio. The MICR duration was set to match energy expenditure of the HIIT session. Hip and knee muscular strength were examined pre and post both HIIT and MICR. Kinematics and running variability for hip and knee, along with spatiotemporal parameters were assessed at start and end of each run-type. Changes in variables were examined using both 2 × 2 ANOVAs with repeated measures and on an individual level when the change in a variable exceeded the minimum detectable change (MDC). RESULTS: All strength measures exhibited significant reductions at the hip and knee (P < 0.05) with time for both run-types; 12% following HIIT, 10.6% post MICR. Hip frontal plane kinematics increased post run for both maximum angle (P < 0.001) and range of motion (P = 0.003). Runners exhibited increased running variability for nearly all variables, with the HIIT having a greater effect. Individual assessment revealed that not all runners were effected post run and that following HIIT more runners had reduced muscular strength, altered kinematics and increased running variability. CONCLUSION: Runners exhibited fatigue induced changes following typical training runs, which could potentially present risk of injury development. Group and individual assessment revealed different findings where the use of MDC is recommended over that of P-values.

Diverse human VH antibody fragments with bio-therapeutic properties from the Crescendo Mouse.

We describe the 'Crescendo Mouse', a human VH transgenic platform combining an engineered heavy chain locus with diverse human heavy chain V, D and J genes, a modified mouse Cγ1 gene and complete 3' regulatory region, in a triple knock-out (TKO) mouse background devoid of endogenous immunoglobulin expression. The addition of the engineered heavy chain locus to the TKO mouse restored B cell development, giving rise to functional B cells that responded to immunization with a diverse response that comprised entirely 'heavy chain only' antibodies. Heavy chain variable (VH) domain libraries were rapidly mined using phage display technology, yielding diverse high-affinity human VH that had undergone somatic hypermutation, lacked aggregation and showed enhanced expression in E. coli. The Crescendo Mouse produces human VH fragments, or Humabody® VH, with excellent bio-therapeutic potential, as exemplified here by the generation of antagonistic Humabody® VH specific for human IL17A and IL17RA.

A mathematical model for quantifying training.

A systems modelling approach has been used to quantify the dose-response nature of training. Considerable attention has been focused on the modelling process with little work on the determination of the training impulse (TRIMP) scores. Currently, the methods employed to calculate TRIMPs are subject to various limitations including the use of generic ordinal category or exponential weighting factors for higher exercise intensities. These weightings are necessary to prevent excessively high scores from long duration, low intensity bouts of exercise. We propose a new method to calculate TRIMP scores based upon a whole body bioenergetic model. Our method is individual specific, removing many of the previous limitations. Furthermore, this model could enable a greater comparison of continuous and interval training methods. This model takes into account the length of repetition(s), concentration of the interval session and mode of recovery. This approach, while requiring further research, offers a potential improvement in the accuracy of training load calculations.

The effect of two plyometric training techniques on muscular power and agility in youth soccer players.

The aim of this study was to compare the effects of two plyometric training techniques on power and agility in youth soccer players. Twelve males from a semiprofessional football club's academy (age = 17.3 +/- 0.4 years, stature = 177.9 +/- 5.1 cm, mass = 68.7 +/- 5.6 kg) were randomly assigned to 6 weeks of depth jump (DJ) or countermovement jump (CMJ) training twice weekly. Participants in the DJ group performed drop jumps with instructions to minimize ground-contact time while maximizing height. Participants in the CMJ group performed jumps from a standing start position with instructions to gain maximum jump height. Posttraining, both groups experienced improvements in vertical jump height (p < 0.05) and agility time (p < 0.05) and no change in sprint performance (p > 0.05). There were no differences between the treatment groups (p > 0.05). The study concludes that both DJ and CMJ plyometrics are worthwhile training activities for improving power and agility in youth soccer players.