Morphomechanical Innovation Drives Explosive Seed Dispersal.

How mechanical and biological processes are coordinated across cells, tissues, and organs to produce complex traits is a key question in biology. Cardamine hirsuta, a relative of Arabidopsis thaliana, uses an explosive mechanism to disperse its seeds. We show that this trait evolved through morphomechanical innovations at different spatial scales. At the organ scale, tension within the fruit wall generates the elastic energy required for explosion. This tension is produced by differential contraction of fruit wall tissues through an active mechanism involving turgor pressure, cell geometry, and wall properties of the epidermis. Explosive release of this tension is controlled at the cellular scale by asymmetric lignin deposition within endocarp b cells-a striking pattern that is strictly associated with explosive pod shatter across the Brassicaceae plant family. By bridging these different scales, we present an integrated mechanism for explosive seed dispersal that links evolutionary novelty with complex trait innovation. VIDEO ABSTRACT.

PLEKHS1 drives PI3Ks and remodels pathway homeostasis in PTEN-null prostate.

The PIP3/PI3K network is a central regulator of metabolism and is frequently activated in cancer, commonly by loss of the PIP3/PI(3,4)P2 phosphatase, PTEN. Despite huge research investment, the drivers of the PI3K network in normal tissues and how they adapt to overactivation are unclear. We find that in healthy mouse prostate PI3K activity is driven by RTK/IRS signaling and constrained by pathway feedback. In the absence of PTEN, the network is dramatically remodeled. A poorly understood YXXM- and PIP3/PI(3,4)P2-binding PH domain-containing adaptor, PLEKHS1, became the dominant activator and was required to sustain PIP3, AKT phosphorylation, and growth in PTEN-null prostate. This was because PLEKHS1 evaded pathway-feedback and experienced enhanced PI3K- and Src-family kinase-dependent phosphorylation of Y258XXM, eliciting PI3K activation. hPLEKHS1 mRNA and activating Y419 phosphorylation of hSrc correlated with PI3K pathway activity in human prostate cancers. We propose that in PTEN-null cells receptor-independent, Src-dependent tyrosine phosphorylation of PLEKHS1 creates positive feedback that escapes homeostasis, drives PIP3 signaling, and supports tumor progression.

An mTORC1-to-CDK1 Switch Maintains Autophagy Suppression during Mitosis.

Since nuclear envelope breakdown occurs during mitosis in metazoan cells, it has been proposed that macroautophagy must be inhibited to maintain genome integrity. However, repression of macroautophagy during mitosis remains controversial and mechanistic detail limited to the suggestion that CDK1 phosphorylates VPS34. Here, we show that initiation of macroautophagy, measured by the translocation of the ULK complex to autophagic puncta, is repressed during mitosis, even when mTORC1 is inhibited. Indeed, mTORC1 is inactive during mitosis, reflecting its failure to localize to lysosomes due to CDK1-dependent RAPTOR phosphorylation. While mTORC1 normally represses autophagy via phosphorylation of ULK1, ATG13, ATG14, and TFEB, we show that the mitotic phosphorylation of these autophagy regulators, including at known repressive sites, is dependent on CDK1 but independent of mTOR. Thus, CDK1 substitutes for inhibited mTORC1 as the master regulator of macroautophagy during mitosis, uncoupling autophagy regulation from nutrient status to ensure repression of macroautophagy during mitosis.

NANOGP1, a tandem duplicate of NANOG, exhibits partial functional conservation in human naïve pluripotent stem cells.

Gene duplication events can drive evolution by providing genetic material for new gene functions, and they create opportunities for diverse developmental strategies to emerge between species. To study the contribution of duplicated genes to human early development, we examined the evolution and function of NANOGP1, a tandem duplicate of the transcription factor NANOG. We found that NANOGP1 and NANOG have overlapping but distinct expression profiles, with high NANOGP1 expression restricted to early epiblast cells and naïve-state pluripotent stem cells. Sequence analysis and epitope-tagging revealed that NANOGP1 is protein coding with an intact homeobox domain. The duplication that created NANOGP1 occurred earlier in primate evolution than previously thought and has been retained only in great apes, whereas Old World monkeys have disabled the gene in different ways, including homeodomain point mutations. NANOGP1 is a strong inducer of naïve pluripotency; however, unlike NANOG, it is not required to maintain the undifferentiated status of human naïve pluripotent cells. By retaining expression, sequence and partial functional conservation with its ancestral copy, NANOGP1 exemplifies how gene duplication and subfunctionalisation can contribute to transcription factor activity in human pluripotency and development.

Mechanism and spectrum of inhibition of a 4´-cyano modified nucleotide analog against diverse RNA polymerases of prototypic respiratory RNA viruses.

The development of safe and effective broad-spectrum antivirals that target the replication machinery of respiratory viruses is of high priority in pandemic preparedness programs. Here, we studied the mechanism of action of a newly discovered nucleotide analog against diverse RNA-dependent RNA polymerases (RdRp) of prototypic respiratory viruses. GS-646939 is the active 5'-triphosphate (TP) metabolite of a 4'-cyano modified C-adenosine analog phosphoramidate prodrug GS-7682. Enzyme kinetics show that the RdRps of human rhinovirus type 16 (HRV-16) and enterovirus 71 (EV-71) incorporate GS-646939 with unprecedented selectivity; GS-646939 is incorporated 20-50-fold more efficiently than its natural ATP counterpart. The RdRp complex of respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) incorporate GS-646939 and ATP with similar efficiency. In contrast, influenza B RdRp shows a clear preference for ATP and human mitochondrial RNA polymerase (h-mtRNAP) does not show significant incorporation of GS-646939. Once incorporated into the nascent RNA strand, GS-646939 acts as a chain-terminator although higher NTP concentrations can partially overcome inhibition for some polymerases. Modeling and biochemical data suggest that the 4'-modification inhibits RdRp translocation. Comparative studies with GS-443902, the active triphosphate form of the 1'-cyano modified prodrugs remdesivir and obeldesivir, reveal not only different mechanisms of inhibition, but also differences in the spectrum of inhibition of viral polymerases. In conclusion, 1'-cyano and 4'-cyano modifications of nucleotide analogs provide complementary strategies to target the polymerase of several families of respiratory RNA viruses.

Strength-trained adults demonstrate greater corticoreticular activation versus untrained controls.

The rapid increase in strength following strength-training involves neural adaptations, however, their specific localisation remains elusive. Prior focus on corticospinal responses prompts this study to explore the understudied cortical/subcortical adaptations, particularly cortico-reticulospinal tract responses, comparing healthy strength-trained adults to untrained peers. Fifteen chronically strength-trained individuals (≥2 years of training, mean age: 24 ± 7 years) were compared with 11 age-matched untrained participants (mean age: 26 ± 8 years). Assessments included maximal voluntary force (MVF), corticospinal excitability using transcranial magnetic stimulation (TMS), spinal excitability (cervicomedullary stimulation), voluntary activation (VA) and reticulospinal tract (RST) excitability, utilizing StartReact responses and ipsilateral motor-evoked potentials (iMEPs) for the flexor carpi radialis muscle. Trained participants had higher normalized MVF (6.4 ± 1.1 N/kg) than the untrained participants (4.8 ± 1.3 N/kg) (p = .003). Intracortical facilitation was higher in the strength-trained group (156 ± 49%) (p = .02), along with greater VA (98 ± 3.2%) (p = .002). The strength-trained group displayed reduced short-interval-intracortical inhibition (88 ± 8.0%) compared with the untrained group (69 ± 17.5%) (p < .001). Strength-trained individuals exhibited a greater normalized rate of force development (38.8 ± 10.1 N·s-1/kg) (p < .009), greater reticulospinal gain (2.5 ± 1.4) (p = .02) and higher ipsilateral-to-contralateral MEP ratios compared with the untrained group (p = .03). Strength-trained individuals displayed greater excitability within the intrinsic connections of the primary motor cortex and the RST. These results suggest greater synaptic input from the descending cortico-reticulospinal tract to α-motoneurons in strength-trained individuals, thereby contributing to the observed increase in VA and MVF.

Social Decision-Making Analysis: A General Approach to Inform Decisions on Resources in the Public Sector.

OBJECTIVES: Public expenditure aims to achieve social objectives by improving a range of socially valuable attributes of benefit (arguments in a social welfare function). Public expenditure is typically allocated to public sector budgets, where budget holders are tasked with meeting a subset of social objectives. METHODS: Decision makers require an evidence-based assessment of whether a proposed investment is likely to be worthwhile given existing levels of public expenditure. However, others also require some assessment of whether the overall level and allocation of public expenditure are appropriate. This article proposes a more general theoretical framework for economic evaluation that addresses both these questions. RESULTS: Using a stylized example of the economic evaluation of a new intervention in a simplified UK context, we show that this more general framework can support decisions beyond the approval or rejection of single projects. It shows that broader considerations about the level and allocation of public expenditure are possible and necessary when evaluating specific investments, which requires evidence of the range of benefits offered by marginal changes in different types of public expenditure and normative choices of how the attributes of benefit gained and forgone are valued. CONCLUSIONS: The proposed framework shows how to assess the value of a proposed investment and whether and how the overall level of public expenditure and its allocation across public sector budgets might be changed. It highlights that cost-benefit analysis and cost-effectiveness analysis can be viewed as special cases of this framework, identifying the weakness with each.

Two-week step-reduction has limited negative effects on physical function and metabolic health in older adults.

PURPOSE: This study determined the effects of a 2-week step-reduction period followed by 4-week exercise rehabilitation on physical function, body composition, and metabolic health in 70-80-year-olds asymptomatic for injury/illness. METHODS: A parallel-group randomized controlled trial (ENDURE-study, NCT04997447) was used, where 66 older adults (79% female) were randomized to either intervention or control group. The intervention group reduced daily steps to < 2000, monitored by accelerometer, for two weeks (Period I) and then step-reduction requirement was removed with an additional exercise rehabilitation 4 times per week for 4 weeks (Period II). The control group continued their habitual physical activity throughout with no additional exercise intervention. Laboratory tests were performed at baseline, after Period I and Period II. The primary outcome measure was leg lean mass (LLM). Secondary outcomes included total lean and fat mass, blood glucose and insulin concentration, LDL cholesterol and HDL cholesterol concentration, maximal isometric leg press force (MVC), and chair rise and stair climb performance. RESULTS: LLM remained unchanged in both groups and no changes occurred in physical function nor body composition in the intervention group in Period I. HDL cholesterol concentration reduced after Period I (from 1.62 ± 0.37 to 1.55 ± 0.36 mmol·L-1, P = 0.017) and returned to baseline after Period II (1.66 ± 0.38 mmol·L-1) in the intervention group (Time × Group interaction: P = 0.065). MVC improved after Period II only (Time × Group interaction: P = 0.009, Δ% = 15%, P < 0.001). CONCLUSION: Short-term step-reduction in healthy older adults may not be as detrimental to health or physical function as currently thought.

Cortical and spinal responses to short-term strength training and detraining in young and older adults in rectus femoris muscle.

INTRODUCTION: Strength training mitigates the age-related decline in strength and muscle activation but limited evidence exists on specific motor pathway adaptations. METHODS: Eleven young (22-34 years) and ten older (66-80 years) adults underwent five testing sessions where lumbar-evoked potentials (LEPs) and motor-evoked potentials (MEPs) were measured during 20 and 60% of maximum voluntary contraction (MVC). Ten stimulations, randomly delivered, targeted 25% of maximum compound action potential for LEPs and 120, 140, and 160% of active motor threshold (aMT) for MEPs. The 7-week whole-body resistance training intervention included five exercises, e.g., knee extension (5 sets) and leg press (3 sets), performed twice weekly and was followed by 4 weeks of detraining. RESULTS: Young had higher MVC (~ 63 N·m, p = 0.006), 1-RM (~ 50 kg, p = 0.002), and lower aMT (~ 9%, p = 0.030) than older adults at baseline. Young increased 1-RM (+ 18 kg, p < 0.001), skeletal muscle mass (SMM) (+ 0.9 kg, p = 0.009), and LEP amplitude (+ 0.174, p < 0.001) during 20% MVC. Older adults increased MVC (+ 13 N·m, p = 0.014), however, they experienced decreased LEP amplitude (- 0.241, p < 0.001) during 20% MVC and MEP amplitude reductions at 120% (- 0.157, p = 0.034), 140% (- 0.196, p = 0.026), and 160% (- 0.210, p = 0.006) aMT during 60% MVC trials. After detraining, young and older adults decreased 1-RM, while young adults decreased SMM. CONCLUSION: Higher aMT and MEP amplitude in older adults were concomitant with lower baseline strength. Training increased strength in both groups, but divergent modifications in cortico-spinal activity occurred. Results suggest that the primary locus of adaptation occurs at the spinal level.

Time Course of Neuromuscular Fatigue During Different Resistance Exercise Loadings in Power Athletes, Strength Athletes, and Nonathletes.

ABSTRACT: Kotikangas, J, Walker, S, Peltonen, H, and Häkkinen, K. Time course of neuromuscular fatigue during different resistance exercise loadings in power athletes, strength athletes, and nonathletes. J Strength Cond Res 38(7): 1231-1242, 2024-Training background may affect the progression of fatigue and neuromuscular strategies to compensate for fatigue during resistance exercises. Thus, our aim was to examine how training background affects the time course of neuromuscular fatigue in response to different resistance exercises. Power athletes (PA, n = 8), strength athletes (SA, n = 8), and nonathletes (NA, n = 7) performed hypertrophic loading (HL, 5 × 10 × 10RM), maximal strength loadings (MSL, 7 × 3 × 3RM) and power loadings (PL, 7 × 6 × 50% of 1 repetition maximum) in back squat. Average power (AP), average velocity (VEL), surface electromyography (sEMG) amplitude (sEMGRMS), and sEMG mean power frequency (sEMGMPF) were measured within all loading sets. During PL, greater decreases in AP occurred from the beginning of SET1 to SET7 and in VEL to both SET4 and SET7 in NA compared with SA (p < 0.01, g > 1.84). During HL, there were various significant group × repetition interactions in AP within and between sets (p < 0.05, ηp2 > 0.307), but post hoc tests did not indicate significant differences between the groups (p > 0.05, g = 0.01-0.93). During MSL and HL, significant within-set and between-set decreases occurred in AP (p < 0.001, ηp2 > 0.701) and VEL (p < 0.001, ηp2 > 0.748) concurrently with increases in sEMGRMS (p < 0.01, ηp2 > 0.323) and decreases in sEMGMPF (p < 0.01, ηp2 > 0.242) in all groups. In conclusion, SA showed fatigue resistance by maintaining higher AP and VEL throughout PL. During HL, PA tended to have the greatest initial fatigue response in AP, but between-group comparisons were nonsignificant despite large effect sizes (g > 0.8). The differences in the progression of neuromuscular fatigue may be related to differing neural activation strategies between the groups, but further research confirmation is required.

Modulation of H-reflex and V-wave responses during dynamic balance perturbations.

Motoneuron excitability is possible to measure using H-reflex and V-wave responses. However, it is not known how the motor control is organized, how the H-reflex and V-wave responses modulate and how repeatable these are during dynamic balance perturbations. To assess the repeatability, 16 participants (8 men, 8 women) went through two, identical measurement sessions with ~ 48 h intervals, where maximal isometric plantar flexion (IMVC) and dynamic balance perturbations in horizontal, anterior-posterior direction were performed. Soleus muscle (SOL) neural modulation during balance perturbations were measured at 40, 70, 100 and 130 ms after ankle movement by using both H-reflex and V-wave methods. V-wave, which depicts the magnitude of efferent motoneuronal output (Bergmann et al. in JAMA 8:e77705, 2013), was significantly enhanced as early as 70 ms after the ankle movement. Both the ratio of M-wave-normalized V-wave (0.022-0.076, p < 0.001) and H-reflex (0.386-0.523, p < 0.001) increased significantly at the latency of 70 ms compared to the latency of 40 ms and remained at these levels at latter latencies. In addition, M-wave normalized V-wave/H-reflex ratio increased from 0.056 to 0.179 (p < 0.001). The repeatability of V-wave demonstrated moderate-to-substantial repeatability (ICC = 0.774-0.912) whereas the H-reflex was more variable showing fair-to-substantial repeatability (ICC = 0.581-0.855). As a conclusion, V-wave was enhanced already at 70 ms after the perturbation, which may indicate that increased activation of motoneurons occurred due to changes in descending drive. Since this is a short time-period for voluntary activity, some other, potentially subcortical responses might be involved for V-wave increment rather than voluntary drive. Our results addressed the usability and repeatability of V-wave method during dynamic conditions, which can be utilized in future studies.

AIM2 Suppresses Inflammation and Epithelial Cell Proliferation during Glomerulonephritis.

Absent in melanoma-2 (AIM2) is an inflammasome-forming innate immune sensor for dsDNA but also exhibits inflammasome-independent functions such as restricting cellular proliferation. AIM2 is expressed in the kidney, but its localization and function are not fully characterized. In normal human glomeruli, AIM2 localized to podocytes. In patients with glomerulonephritis, AIM2 expression increased in CD44+-activated parietal epithelial cells within glomerular crescents. To explore AIM2 effects in glomerular disease, studies in Aim2 -/- mice were performed. Aim2-/- glomeruli showed reduced expression of Wilm tumor gene-1 (WT1), WT1-driven podocyte genes, and increased proliferation in outgrowth assays. In a nephrotoxic serum (NTS)-induced glomerulonephritis model, Aim2-/- (B6) mice exhibited more severe glomerular crescent formation, tubular injury, inflammation, and proteinuria compared with wild-type controls. Inflammasome activation markers were absent in both Aim2 -/- and wild-type kidneys, despite an increased inflammatory transcriptomic signature in Aim2 -/- mice. Aim2 -/- mice also demonstrated dysregulated cellular proliferation and an increase in CD44+ parietal epithelial cells during glomerulonephritis. The augmented inflammation and epithelial cell proliferation in Aim2 -/- (B6) mice was not due to genetic background, as Aim2 -/- (B6.129) mice demonstrated a similar phenotype during NTS glomerulonephritis. The AIM2-like receptor (ALR) locus was necessary for the inflammatory glomerulonephritis phenotype observed in Aim2 -/- mice, as NTS-treated ALR -/- mice displayed equal levels of injury as wild-type controls. Podocyte outgrowth from ALR -/- glomeruli was still increased, however, confirming that the ALR locus is dispensable for AIM2 effects on epithelial cell proliferation. These results identify a noncanonical role for AIM2 in suppressing inflammation and epithelial cell proliferation during glomerulonephritis.

Supporting the revision of the health benefits package in Uganda: A constrained optimisation approach.

This study demonstrates how the linear constrained optimization approach can be used to design a health benefits package (HBP) which maximises the net disability adjusted life years (DALYs) averted given the health system constraints faced by a country, and how the approach can help assess the marginal value of relaxing health system constraints. In the analysis performed for Uganda, 45 interventions were included in the HBP in the base scenario, resulting in a total of 26.7 million net DALYs averted. When task shifting of pharmacists' and nutrition officers' tasks to nurses is allowed, 73 interventions were included in the HBP resulting in a total of 32 million net DALYs averted (a 20% increase). Further, investing only $58 towards hiring additional nutrition officers' time could avert one net DALY; this increased to $60 and $64 for pharmacists and nurses respectively, and $100,000 for expanding the consumable budget, since human resources present the main constraint to the system.

Smart wing rotation and trailing-edge vortices enable high frequency mosquito flight.

Mosquitoes exhibit unusual wing kinematics; their long, slender wings flap at remarkably high frequencies for their size (>800 Hz)and with lower stroke amplitudes than any other insect group. This shifts weight support away from the translation-dominated, aerodynamic mechanisms used by most insects, as well as by helicopters and aeroplanes, towards poorly understood rotational mechanisms that occur when pitching at the end of each half-stroke. Here we report free-flight mosquito wing kinematics, solve the full Navier-Stokes equations using computational fluid dynamics with overset grids, and validate our results with in vivo flow measurements. We show that, although mosquitoes use familiar separated flow patterns, much of the aerodynamic force that supports their weight is generated in a manner unlike any previously described for a flying animal. There are three key features: leading-edge vortices (a well-known mechanism that appears to be almost ubiquitous in insect flight), trailing-edge vortices caused by a form of wake capture at stroke reversal, and rotational drag. The two new elements are largely independent of the wing velocity, instead relying on rapid changes in the pitch angle (wing rotation) at the end of each half-stroke, and they are therefore relatively immune to the shallow flapping amplitude. Moreover, these mechanisms are particularly well suited to high aspect ratio mosquito wings.

Epistemic problems with mental health legislation in the doctor-patient relationship.

Mental health legislation that requires patients to accept 'care' has come under increasing scrutiny, prompted primarily by a human rights ethic. Epistemic issues in mental health have received some attention, however, less attention has been paid to the possible epistemic problems of mental health legislation existing. In this manuscript, we examine the epistemic problems that arise from the presence of such legislation, both for patients without a prior experience of being detained under such legislation and for those with this experience. We also examine how the doctor is legally obligated to compound the epistemic problems by the knowledge they prioritise and the failure to generate new knowledge. Specifically, we describe the problems of testimonial epistemic injustice, epistemic silencing, and epistemic smothering, and address the possible justification provided by epistemic paternalism. We suggest that there is no reasonable epistemic justification for mental health legislation that creates an environment that fundamentally unbalances the doctor-patient relationship. Significant positive reasons to counterbalance this are needed to justify the continuation of such legislation.

Contraction intensity modulates spinal excitability during transcranial magnetic stimulation-evoked silent period in rectus femoris muscle.

PURPOSE: Reduced spinal excitability during the transcranial magnetic stimulation (TMS) silent period (SP) has recently been shown to last longer than previously thought in the upper limbs, as assessed via spinal electrical stimulation. Further, there is reason to expect that contraction intensity affects the duration of the reduced spinal excitability. METHODS: This study investigated spinal excitability at different time delays within the TMS-evoked SP in m.rectus femoris. Fifteen participants performed non-fatiguing isometric knee extensions at 25%, 50% and 75% of maximum voluntary contraction (MVC). Lumbar stimulation (LS) induced a lumbar-evoked potential (LEP) of 50% resting M-max. TMS stimulator output induced a SP lasting ~ 200 ms. In each contraction, a LEP (unconditioned) was delivered ~ 2-3 s prior to TMS, which was followed by a second LEP (conditioned) 60, 90, 120 or 150 ms into the silent period. Five contractions were performed at each contraction intensity and for each time delay in random order. RESULTS: Compared to the unconditioned LEP, the conditioned LEP amplitude was reduced (- 28 ± 34%, p = 0.007) only at 60 ms during 25% of MVC. Conditioned LEP amplitudes during 50% and 75% of MVC were reduced at 60 ms (- 37 ± 47%, p = 0.009 and - 37 ± 42%, p = 0.005, respectively) and 150 ms (- 30% ± 37%, p = 0.0083 and - 37 ± 43%, p = 0.005, respectively). LEP amplitude at 90 ms during 50% of MVC also reduced (- 25 ± 35%, p = 0.013). CONCLUSION: Reduced spinal excitability is extended during 50% and 75% of MVC. In future, paired TMS-LS could be a potential method to understand changes in spinal excitability during SP (at different contraction intensities) when testing various neurophysiological phenomena.

Strategies to improve the success of fixed-time artificial insemination in the ewe.

During the sheep breeding season, ovulatory follicles vary widely in age at pessary removal impacting both the timing of oestrus and pregnancy rates following artificial insemination (AI). Ovulatory follicles that emerge between days 7 to 9 of the pessary period are associated with higher fertility whilst those that emerge earlier or later are associated with lower fertility. In this study, two strategies to improve the success of AI by controlling the development of the ovulatory follicle were examined. In the first, ewes were treated with PGF2α at either -12 and/or +6 days (experiment 1) or -27 days (experiment 2) relative to pessary insertion to control the time of emergence of the ovulatory follicle. In the second, ewes were treated with eCG (400 IU per ewe) at either 0 h, -6 h or -12 h relative to pessary removal (experiment 3) to improve the development of young ovulatory follicles. PGF2α administered on day -27 increased the percentage of pregnant ewes by 17.8% and the number of foetuses per 100 ewes inseminated by 33.9%. PGF2α treatment at other times had either no effect or reduced fertility. During the breeding season, treatment with eCG at -12 h improved the synchrony of oestrus, reduced the size of the ovulatory follicle but did not improve pregnancy rate compared with other treatments. Treatment had no effect during the non-breeding season, supporting earlier findings that the quality of young ovulatory follicles differs during the year. In conclusion, PGF2α treatment 27 days before pessary insertion provides a new and cheap strategy to improve the success of fixed-time AI programs.

Physical qualities and body composition predictors of running performance in national level women's official soccer matches.

The purpose of the study was to (1) determine match running performance, anthropometry and various physical qualities of national level women soccer players and (2) identify key physical qualities and anthropometric predictors of match running profile during a competitive season. Twenty-five national level Finnish soccer players participated in the study. Players performed countermovement jump, loaded squat jumps, 30-meter sprint, maximum isokinetic knee flexor and extensor contractions, an incremental treadmill test and underwent body composition assessment in the lab. Match running performance was analyzed from 115 match observations during competitive league matches over 11 weeks after the laboratory tests. Pearson's correlation was used to determine bivariate relationships between match running variables and physical qualities and anthropometric variables. Identified significant bivariate relationships were then entered into multiple regression analyses to identify the best predictors of match running performance. Physical qualities and anthropometric variables predicted 65% of very high-intensity (VHIR) (> 19 km/h) and 63% of high-intensity (HIR) (13-19 km/h) running distances covered during matches, but only 22% of low-intensity (LIR) and 43% of total distances. Body fat percentage and high-speed knee flexor concentric strength were the most important predictors to VHIR and HIR while aerobic capacity-related variables were most important predictors to LIR and total distance. Physical qualities and anthropometry can predict a large portion of players' VHIR and HIR performance during matches in women's national level soccer. To increase player's VHIR and HIR distance, coaches could aim to develop players' high-speed (especially knee flexor concentric) strength and optimize player's body composition.

Acute neuromuscular and hormonal responses to 20 versus 40% velocity loss in males and females before and after 8 weeks of velocity-loss resistance training.

NEW FINDINGS: What is the central question of this study? Do males and females differ in fatiguability during dynamic loadings, and what are the acute neuromuscular and hormonal responses to 20 versus 40% velocity-loss resistance loadings? How does an 8-week velocity-loss resistance training period modify acute neuromuscular and hormonal responses in males and females? What is the main finding and its importance? Using resistance training methods that regulated the within-set fatigue limit, males appeared to be more susceptible to fatigue than females before the training period. This between-sex difference was diminished after training. The predominant mechanisms of fatigue from 20 and 40% velocity-based resistance training appear to be within the musculature. ABSTRACT: Scientific examination of velocity-based resistance training (VBRT) has increased recently, but how males and females respond to different VBRT protocols or how these acute responses are modified after a period of training is unknown. Habitually resistance-trained males and females followed either a 20 or 40% velocity-loss programme for 8 weeks. Acute squat loading tests (five sets, 70% one-repetition maximum load, 3 min rest) were performed before and after the training period. Tests of maximum neuromuscular performance and blood sampling were conducted before, within 10 min of completion (POST) and 24 h after each acute loading test. Testing included countermovement jump, resting femoral nerve electrical stimulation and bilateral isometric leg press. Blood samples were analysed for whole-blood lactate, serum testosterone, cortisol, growth hormone and creatine kinase concentrations. Countermovement jump height, maximum isometric bilateral leg-press force and the force from a 10 Hz doublet decreased in all groups at POST after 20 and 40% velocity loss. Only males showed reduced force from the 100 Hz doublet and voluntary force over 100 ms at POST before training. The 40% velocity loss led to increased blood lactate and growth hormone responses before training in both males and females. After training, more systematic and equivalent responses in force over 100 ms, force from a 100 Hz doublet and blood lactate were observed regardless of sex/VBRT protocol. Overall, acute responses were greater from 40% VBRT, and males were more susceptible to acute loss in force production capacity before the training period. These VBRT protocol- and sex-related differences were diminished after training.

Study Protocol. Evaluating the life-course health impact of a city-wide system approach to improve air quality in Bradford, UK: A quasi-experimental study with implementation and process evaluation.

BACKGROUND: Air quality is a major public health threat linked to poor birth outcomes, respiratory and cardiovascular disease, and premature mortality. Deprived groups and children are disproportionately affected. Bradford will implement a Clean Air Zone (CAZ) as part of the Bradford Clean Air Plan (B-CAP) in 2022 to reduce pollution, providing a natural experiment. The aim of the current study is to evaluate the impact of the B-CAP on health outcomes and air quality, inequalities and explore value for money. An embedded process and implementation evaluation will also explore barriers and facilitators to implementation, impact on attitudes and behaviours, and any adverse consequences. METHODS: The study is split into 4 work packages (WP). WP1A: 20 interviews with decision makers, 20 interviews with key stakeholders; 10 public focus groups and documentary analysis of key reports will assess implementation barriers, acceptability and adverse or unanticipated consequences at 1 year post-implementation (defined as point at which charging CAZ goes 'live'). WP1B: A population survey (n = 2000) will assess travel behaviour and attitudes at baseline and change at 1 year post-implementation). WP2: Routine air quality measurements will be supplemented with data from mobile pollution sensors in 12 schools collected by N = 240 pupil citizen scientists (4 within, 4 bordering and 4 distal to CAZ boundary). Pupils will carry sensors over four monitoring periods over a 12 month period (two pre, and two post-implementation). We will explore whether reductions in pollution vary by CAZ proximity. WP3A: We will conduct a quasi-experimental interrupted time series analysis using a longitudinal routine health dataset of > 530,000 Bradford residents comparing trends (3 years prior vs 3 years post) in respiratory health (assessed via emergency/GP attendances. WP3B: We will use the richly-characterised Born in Bradford cohort (13,500 children) to explore health inequalities in respiratory health using detailed socio-economic data. WP4: will entail a multi-sectoral health economic evaluation to determine value for money of the B-CAP. DISCUSSION: This will be first comprehensive quasi-experimental evaluation of a city-wide policy intervention to improve air quality. The findings will be of value for other areas implementing this type of approach. TRIAL REGISTRATION: ISRCTN67530835 https://doi.org/10.1186/ISRCTN67530835.