Training Response Research Articles

An algorithmic study of periodization strategy optimization in combined anaerobic and anaerobic fitness training for improving athletes’ endurance qualities

Abstract The principle of flexibility and change should be adopted in the process of physical training, and the optimization of periodization training strategy can only be reasonably carried out according to the specific training response of athletes in order to improve the overall athletic ability of athletes. This paper utilizes the sports training pyramid as a guide, scrutinizes the endurance qualities athletes should possess, and suggests an optimization process for the periodization training strategy, which integrates multiple elements of periodization training. Based on the physiological characteristic indexes of athletes’ cardiorespiratory endurance, a model of cardiorespiratory endurance with different periodization training and different frequencies was established, and the results of the model were inputted into a BP network model optimized by the artificial fish swarm algorithm, thus realizing the prediction of the athletes’ cardiorespiratory endurance. The maximum value of the athletes’ endurance predicted by the ASFA-BP model was 81.09N, which differed from the actual value of the athletes’ endurance only by 1.58%, and the difference in the average lung capacity index (ALCI) was only 1.58%. The difference in mean spirometry index fluctuated between [0.16 mL/kg and 0.29 mL/kg]. The optimal duration of the periodization training strategy based on the acquired endurance data was between 10 and 18 days, and the exercise training load should be reduced by approximately 46% to 65%. The effective prediction of athletes’ endurance quality can help optimize the periodization training strategy and improve athletes’ competitive level faster.

Association of the G>A (rs6265) polymorphism in the brain derived neurotrophic factor gene (BDNF) with post-training changes in Caucasian women

The brain-derived neurotrophic factor (BDNF) rs6265 (G196A; Val66Met) polymorphism has been associated with obesity and type 2 diabetes, with contradictory results involving either A or G as the risk allele. The main aim of this study was to examine whether the BDNF rs6265 polymorphism would influence the efficiency of a training program. An additional aim was to determine whether selected polymorphism can be used as a genetic marker for obesity-related parameters. We studied the genotype distribution in a group of 160 Caucasian females in whom body mass and composition parameters, lipid profile, and glucose levels were measured before and after the 12-week aerobic training program. The majority of obesity-related parameters significantly changed during the intervention (main effect of training); however, the training response was not modulated by genotype (non-significant genotype × training interactions). We also did not find an effect of genotype on selected parameters. Our study showed that the rs6265 polymorphism does not affect the efficiency of the applied training program and is not a good genetic marker for assessing the obesity-related parameters in the studied population. However, we confirmed that regular physical activity is associated with an improvement in obesity-related parameters, which is an important observation for public health.

Dynamics model and vibrational response analysis of helical gear-rotor-bearing transmission system

As a core component of wind turbines, wind power gear speed increasers often work in harsh environments, so it is necessary to study the vibration characteristics of gear transmission systems. Taking a wind turbine gearbox high-speed stage helical gear transmission system as the research object, the dynamics model of multi-degree-of-freedom helical gear-rotor-bearing transmission system is established by the lumped parameter method and solved by Runge-Kutta method, taking into account the tooth side clearance of the gear, transmission error, eccentricity and support force of the nonlinear bearing. The effects of input torque, transmission error and tooth side clearance on the vibration characteristic response of the helical gear train were analyzed. The relationship between the trend of amplitude change in each direction of the gear and the trend of change in the major frequency components was analyzed under the conditions of changing internal and external excitation. The results show that torsional vibration dominates in the system. As the input torque increases, the vibration amplitude of the driving and driven gears decreases, and the frequency amplitude decreases significantly at multiple locations. Gear transmission errors and changes in tooth side clearance have significant effects on gear vibration amplitudes, but are sensitive only to the meshing frequency. The trend of gear vibration amplitude caused by the change of external excitation of the gear set is synchronized with the trend of main frequency amplitude in the corresponding direction, while the change of vibration amplitude caused by internal excitation is consistent with the trend of mesh frequency amplitude in the corresponding direction. The results of this paper can pave a certain foundation for the design and fault diagnosis of wind power gearbox transmission system.

A test of the role of stimulus-response and stimulus-outcome associations in the effects of intermittent-access training

Increased reinforcer motivation in rats has been repeatedly demonstrated following intermittent-access (IntA) training, where the reinforcer is only available for brief periods during a session, compared to continuous-access (ContA) training where the reinforcer is available throughout the session. The present study investigated whether different associations learned during training on the two procedures contributes to the effect. Two experiments tested the importance of the stimulus-response (S-R) and stimulus-outcome (S-O) associations between the IntA availability cues and the training response and reinforcer, respectively. In Exp. 1, separate groups of rats were trained to lever press for saccharin on the IntA or ContA procedures. Increased motivation for saccharin was observed in the IntA group on a later progressive ratio test where nosepoking was the operant (but not when lever pressing was the operant). The outcome of the nosepoke test suggests that a potential S-R association formed during IntA training was not critical for the effect. In Exp. 2, increased saccharin motivation (on nosepoke tests) after IntA training (with lever pressing) was observed regardless of the presence or absence of IntA availability cues, indicating that the S-O association formed during training is not critical for the effect either. Overall, these results suggest that the elemental associations learned on IntA procedures may not be what drives increased motivation observed after IntA training.

O6-methylguanine DNA methyltransferase regulates β-glucan-induced trained immunity of macrophages via farnesoid X receptor and AMPK

Trained immunity is the heightened state of innate immune memory that enhances immune response resulting in nonspecific protection. Epigenetic changes and metabolic reprogramming are critical steps that regulate trained immunity. In this study, we reported the involvement of O6-methylguanine DNA methyltransferase (MGMT), a DNA repair enzyme of lesion induced by alkylating agents, in regulation the trained immunity induced by β-glucan (BG). Pharmacological inhibition or silencing of MGMT expression altered LPS stimulated pro-inflammatory cytokine productions in BG-trained bone marrow derived macrophages (BMMs). Targeted deletion of Mgmt in BMMs resulted in reduction of the trained responses both invitro and invivo models. The transcriptomic analysis revealed that the dampening trained immunity in MGMT KO BMMs is partially mediated by ATM/FXR/AMPK axis affecting the MAPK/mTOR/HIF1α pathways and the reduction in glycolysis function. Taken together, a failure to resolve a DNA damage may have consequences for innate immune memory.

Abstract C176: Cancer-specific AI identifies multi-modal biomarkers of therapeutic response for 1,951 drugs including TNG348, a highly selective USP1 inhibitor

Abstract Understanding drug mechanism-of-action and improving clinical response rates are critical challenges to cancer therapeutic development. We designed a deep learning framework that learns molecular mechanisms of drug sensitivity and resistance from preclinical and/or clinical drug response data. The trained model can then generate biomarker strategies, suggest companion diagnostics, and propose rational drug-drug combinations that increase or restore drug sensitivity. The key innovation is the model’s architecture; the framework learns an embedding that reflects an interpretable relationship between a cellular process and drug response by emulating a tumor cell’s proteomic architecture. We applied the framework to learn genetic determinants of response for 1,951 drugs and 17,386 CRISPR gene knockouts screened in human cancer cell lines. The learned embeddings reflected known and novel mechanisms. RAF inhibitors, MEK inhibitors, and BRAF CRISPR knockout colocalized (P=1.7×10-11) due to their shared dependency on hyperactivation of RAF signaling. CDK4/6 inhibitor efficacy was strongly associated with a set of physically interacting proteins that control G1-to-S transition (P=5.6×10-12). Validating the clinical applicability of the finding, the trained model stratified patient response in a retrospective analysis of 70 ER+ metastatic breast cancer patients treated with the CDK4/6 inhibitor palbociclib (P=0.05, log-rank predicted responsive vs. non-responsive). As a case study, we examined mechanisms of sensitivity and resistance to TNG348 – a potent and highly selective USP1 inhibitor – in non-small cell lung cancer (NSCLC). By integrating genetics, gene expression, and CRISPR screens, the model identified seven genes whose expression explained >50% of the variation in response to TNG348 across 32 held-out NSCLC cell lines (Spearman R=0.74; P=8.7×10-7). The findings extend TNG348’s known relationship with homologous repair to additional protein complexes involved in cell cycle and DNA repair. The model leveraged the new associations to generate a six-biomarker inclusion-exclusion logic that captures both a large population (31.4% of TCGA lung adenocarcinoma patients meet inclusion criteria) and substantially enriches for strong response amongst preclinical models (OR=14.8, P=3.0×10-3). Finally, we asked the model to design rational combinations to overcome acquired resistance mechanisms. Proposed combinations included clinically successful combinations such as RAF+MEK inhibitors and were enriched for synergistic matches in a cell line screen of 986 drug pairings (Spearman rho P=6.6×10-4). These results highlight the promise of explainable AI to learn complex cellular mechanisms-of-action and generate non-obvious biomarker hypothesis and rational drug combination strategies for clinical development. Citation Format: Adam Yaari, Lee McDaniel, Antoine Simoneau, Samuel Meier, Oliver Priebe, Eduardo Farias, Alan Huang, Jannik Andersen, Yi Yu, Maxwell Sherman. Cancer-specific AI identifies multi-modal biomarkers of therapeutic response for 1,951 drugs including TNG348, a highly selective USP1 inhibitor [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C176.

Mucosal recombinant BCG vaccine induces lung-resident memory macrophages and enhances trained immunity via mTORC2/HK1-mediated metabolic rewiring

Bacillus Calmette–Guérin (BCG) vaccination induces a type of immune memory known as “trained immunity”, characterized by the immunometabolic and epigenetic changes in innate immune cells. However, the molecular mechanism underlying the strategies for inducing and/or boosting trained immunity in alveolar macrophages remains unknown. Here, we found that mucosal vaccination with the recombinant strain rBCGPPE27 significantly augmented the trained immune response in mice, facilitating a superior protective response against Mycobacterium tuberculosis and non-related bacterial reinfection in mice when compared to BCG. Mucosal immunization with rBCGPPE27 enhanced innate cytokine production by alveolar macrophages associated with promoted glycolytic metabolism, typical of trained immunity. Deficiency of the mammalian target of rapamycin complex 2 and hexokinase 1 abolished the immunometabolic and epigenetic rewiring in mouse alveolar macrophages after mucosal rBCGPPE27 vaccination. Most noteworthy, utilizing rBCGPPE27’s higher-up trained effects: The single mucosal immunization with rBCGPPE27-adjuvanted coronavirus disease (CoV-2) vaccine raised the rapid development of virus-specific immunoglobulin G antibodies, boosted pseudovirus neutralizing antibodies, and augmented T helper type 1-biased cytokine release by vaccine-specific T cells, compared to BCG/CoV-2 vaccine. These findings revealed that mucosal recombinant BCG vaccine induces lung-resident memory macrophages and enhances trained immunity via reprogramming mTORC2- and HK-1-mediated aerobic glycolysis, providing new vaccine strategies for improving tuberculosis (TB) or coronavirus variant vaccinations, and targeting innate immunity via mucosal surfaces.

Maximal Expiratory Pressure and Its Link With Cough Airflow Before and After Expiratory Muscle Strength Training in Parkinson's Disease

Purpose: Expiratory muscle strength training (EMST) improves maximal expiratory pressure (MEP), and several researchers have reported improvements to voluntary cough airflow in people with Parkinson's disease (PD). However, the link between the change in MEP and cough and whether patient-specific factors impact the training response is not well understood. Therefore, study aims were to examine (a) the relationship between MEP and cough pre- and post-EMST, (b) the associations between the change in MEP and change in cough, and (c) if patient-specific factors predict the change MEP. Method: This is a secondary analysis of data from 30 people with PD who completed MEP and voluntary and reflex cough testing via spirometry pre– and post–5 weeks of EMST. Pearson's r correlations were used for Aims 1 and 2. Multivariable linear regression was used for Aim 3. Results: Pre-EMST correlations between MEP and cough as well as correlations between the change in MEP and change in cough were nonsignificant. Post-EMST, MEP was correlated with voluntary cough expired volume (CEV, r = .58 , p < .001), peak expiratory flow rate (PEFR, r = .56 , p = .001), and cough volume acceleration ( r = .47 , p = .009 ) , as well as reflex CEV ( r = .5, p = .005). Patient-specific factors did not predict the change in MEP. Conclusions: This study showed that there was a larger correlation between expiratory muscle strength and cough airflow post-EMST than pre-EMST for voluntary and reflex cough in PD; however, the correlation between the change was small. Future research is needed to identify additional physiologic changes that are impacting cough airflow after EMST. Supplemental Material: https://doi.org/10.23641/asha.24602565

Acid ceramidase regulates innate immune memory

Innate immune memory, also called "trained immunity," is a functional state of myeloid cells enabling enhanced immune responses. This phenomenon is important for host defense, but also plays a role in various immune-mediated conditions. We show that exogenously administered sphingolipids and inhibition of sphingolipid metabolizing enzymes modulate trained immunity. In particular, we reveal that acid ceramidase, an enzyme that converts ceramide to sphingosine, is a potent regulator of trained immunity. We show that acid ceramidase regulates the transcription of histone-modifying enzymes, resulting in profound changes in histone 3 lysine 27 acetylation and histone 3 lysine 4 trimethylation. We confirm our findings by identifying single-nucleotide polymorphisms in the region of ASAH1, the gene encoding acid ceramidase, that are associated with the trained immunity cytokine response. Our findings reveal an immunomodulatory effect of sphingolipids and identify acid ceramidase as a relevant therapeutic target to modulate trained immunity responses in innate immune-driven disorders.

Training Load Is Correlated with Changes in Creatine Kinase and Wellness over a 12-Week Multi-Stage Preparatory Training Block for a Major Competition in International Boxers

Background: There are no published data on the training-load magnitude or distribution in elite international-level boxers preparing for a major competition nor on the training load’s relationship with objective and subjective training markers. Methods: Twelve elite boxers (eight males and four females) preparing for the 2018 Commonwealth Games were monitored during training for 12 weeks. The training load (TL), change in creatine kinase (ΔCK), and wellness variables were measured daily but were amalgamated into average weekly values over the 12-week period for weekly comparisons. The relationships between the TL, ΔCK, and wellness variables were also assessed. Results: The significant (p < 0.001) main effects of the week with large and moderate effect sizes were noted for the TL and ΔCK, respectively, with weeks 9 and 12 in the competition-specific and taper phases showing the greatest differences, respectively. For wellness, only the muscle condition showed a significant change over time (p < 0.001). There were significant (p < 0.05) small–moderate correlations between the TL, ΔCK, and wellness variables. Conclusions: This is the first study to describe the weekly training loads and responses to training of elite international boxers across a 12-week pre-competition training period in preparation for a major competition. The findings within this study report that elite international boxers have high chronic training loads that change between training blocks to put emphasis on different qualities. Monitoring the indirect muscle damage through CK may provide further information on the internal training responses in boxers.

Fatty acid desaturation and lipoxygenase pathways support trained immunity

Infections and vaccines can induce enhanced long-term responses in innate immune cells, establishing an innate immunological memory termed trained immunity. Here, we show that monocytes with a trained immunity phenotype, due to exposure to the Bacillus Calmette-Guérin (BCG) vaccine, are characterized by an increased biosynthesis of different lipid mediators (LM) derived from long-chain polyunsaturated fatty acids (PUFA). Pharmacological and genetic approaches show that long-chain PUFA synthesis and lipoxygenase-derived LM are essential for the BCG-induced trained immunity responses of human monocytes. Furthermore, products of 12-lipoxygenase activity increase in monocytes of healthy individuals after BCG vaccination. Grasping the underscoring lipid metabolic pathways contributes to our understanding of trained immunity and may help to identify therapeutic tools and targets for the modulation of innate immune responses.

Eight weeks of heavy strength training increases hemoglobin mass and V̇o2peak in well-trained to elite female and male rowers.

O2-transport and endurance exercise performance are greatly influenced by hemoglobin mass (Hbmass), which largely depends on lean body mass (LBM). This study investigated the effects of 8 wk with three weekly sessions of conventional (3-SET: 3 × 10 reps) or high-volume strength training (10-SET: 5-10 × 10 reps) on LBM, Hbmass, muscle strength, and exercise performance in female and male rowers. Hematological parameters were obtained through CO rebreathing and body composition by dual-energy X-ray absorptiometry (DEXA) scans before and after the training period. Concomitantly, V̇o2peak was determined during 2-km ergometer rowing and muscle strength by isometric midthigh pull. There were no differences in training responses between groups for any of the parameters. Pooled data revealed overall increments for Hbmass (10-SET: 882 ± 199 g to 897 ± 213 g; 3-SET: 936 ± 245 g to 962 ± 247 g, P = 0.02) and V̇o2peak (10-SET: 4.3 ± 1.0 to 4.4 ± 0.9 L·min-1; 3-SET: 4.5 ± 0.9 to 4.6 ± 0.9 L·min-1, P = 0.03), whereas LBM remained unchanged (10-SET: 58.7 ± 10.5 to 58.7 ± 10.1 kg; 3-SET: 64.1 ± 10.8 to 64.5 ± 10.6 kg, P = 0.42). Maximal isometric midthigh pull strength increased (10-SET: 224 ± 47 kg to 237 ± 55 kg; 3-SET: 256 ± 77 kg to 281 ± 83 kg, P = 0.001). Strong associations were observed between LBM and Hbmass and V̇o2peak (r2 = 0.88-0.90), entailing sex differences in Hbmass and V̇o2peak. Normalizing V̇o2peak to LBM reduced the sex difference to ∼10%, aligning with the sex difference in Hbmass·LBM-1. Strength training successfully increased Hbmass and V̇o2peak in elite female and male rowers, without an additional effect from increased training volume. Moreover, sex differences in V̇o2peak were mainly explained by differences in LBM, but likely also by differences in Hbmass·LBM-1.NEW & NOTEWORTHY This study in female and male rowers demonstrates that hemoglobin mass (Hbmass), V̇o2peak, and muscle strength increases with 8 wk of heavy strength training and that this response is not different between conventional (3 × 10 repetitions) and high-volume strength training (10 × 10 repetitions). Moreover, female rowers exhibited less hemoglobin per kilogram of lean body mass compared with their male counterparts, which likely contributes to sex differences in V̇o2peak and rowing performance.

Abstract 16612: Cardiomyocyte PGC-1α Prevents Cardiac Atrophy and Failure in Response to Endurance Exercise Training

Introduction: Aerobic exercise promotes physiologic hypertrophy of the heart in healthy individuals. In skeletal muscle and heart, a key orchestrator of the adaptation to exercise is the transcriptional regulator PGC-1α. PGC-1α may mediate cardiac adaptation to physiological stress through myriad mechanisms. The role of cardiac PGC-1α to the systemic training response is poorly understood. Methods: We generated PGC-1α cardiomyocyte-specific knockout (KO) mice to study its role in endurance exercise. We also silenced Ppargc1a expression in a cell model of physiologic cardiomyocyte hypertrophy. Results: Sedentary KO mice demonstrated normal cardiac function and minimal differences in acute exercise tolerance. However, KO mice demonstrated a lack of ability to augment exercise capacity after 6 weeks of wheel running (work achieved 32.9 J in WT [39% increase] vs 23.1 J in KOs [no change vs baseline], p<0.001, unpaired t-test). This was despite comparable voluntary wheel distance run during training (2.93-3.67 km/day for both over 5 weeks, p=0.58). Unexpectedly, after 6 weeks of training, KO mice developed a dilated cardiomyopathy and exercise-related dysfunction (contractile reserve [ΔFS stress-rest ] +6.0 in WT vs -6.4% in KO, p<0.05, unpaired t-test). They also demonstrated features of cardiac cachexia as measured by 27% and 19% reductions in inguinal adipose and gastrocnemius mass, respectively (P<0.05, unpaired t-test). RNA sequencing of the hearts from these mice demonstrated activation of pathological ( Nppa , Nppb , Myh7/Myh6 ), fibrotic and atrophic secreted factors ( Gdf15 , Fstl3 ). Silencing Ppargc1a in rat cardiomyocytes after IGF1 treatment failed to induce physiologic hypertrophy and activated fibrotic programs and conferred atrophy. Conclusions: Our studies posit cardiomyocyte PGC-1α as a key mediator of the adaptive response to exercise training and unveil its central role in protecting from exercise-related cardiac atrophy and fibrosis.

Multiverse Recurrent Expansion With Multiple Repeats: A Representation Learning Algorithm for Electricity Theft Detection in Smart Grids

Electricity theft, known as “Non-Technical Loss” (NTL) is certainly one of the priorities of power distribution utilities. Indeed, NTL could lead to serious damage ranging from massive financial losses to loss of reputation resulting from poor power quality. With advances in metering infrastructure technologies, the availability of user data has fueled the emergence of data-driven methods in NTL detection. Among these methods, deep learning (DL) is an indisputable alternative to conventional human-centric approaches. Typically, modeling based on NTL data is subject to three main challenges, including (i) missing information; (ii) class imbalance; and (iii) data complexity. In this context, this paper contributes to solving these three main problems while paying more attention to data complexity related to cardinality. Accordingly, a multiverse recurrent expansion with multiple repeats (MV-REMR) algorithm is proposed in this paper. MV-REMR is able to provide deeper representations than ordinary DL networks and take advantage of different trained deep network responses to build an efficient model. For MV-REMR efficiency analysis, a realistic NTL dataset is considered. As a result, MV-REMR has shown that it can achieve what is considered excellent feature mapping proven by both scatter visualization and variations in widely used classification metrics. Moreover, MV-REMR shows its ability to marginalize the distance of data classes with superior performance. In addition, thanks to the new mapping scheme, MV-REMR shows its ability to correct outliers resulting from errors in missing values filling techniques. Finally, a comparison with some recent successful works also confirms the superiority of the MV-REMR model.

Introducing the STReaC (Spike Train Response Classification) toolbox

Background:This work presents a toolbox that implements methodology for automated classification of diverse neural responses to optogenetic stimulation or other changes in conditions, based on spike train recordings. New Method:The toolbox implements what we call the Spike Train Response Classification algorithm (STReaC), which compares measurements of activity during a baseline period with analogous measurements during a subsequent period to identify various responses that might result from an event such as introduction of a sustained stimulus. The analyzed response types span a variety of patterns involving distinct time courses of increased firing, or excitation, decreased firing, or inhibition, or combinations of these. Excitation (inhibition) is identified from a comparative analysis of the spike density function (interspike interval function) for the baseline period relative to the corresponding function for the response period. Results:The STReaC algorithm as implemented in this toolbox provides a user-friendly, tunable, objective methodology that can detect a variety of neuronal response types and associated subtleties. We demonstrate this with single-unit neural recordings of rodent substantia nigra pars reticulata (SNr) during optogenetic stimulation of the globus pallidus externa (GPe). Comparison with existing methods:In several examples, we illustrate how the toolbox classifies responses in situations in which traditional methods (spike counting and visual inspection) either fail to detect a response or provide a false positive. Conclusions:The STReaC toolbox provides a simple, efficient approach for classifying spike trains into a variety of response types defined relative to a period of baseline spiking.

Resistance training and hematological responses

Aplastic anemia is a hematopoietic dysfunction that compromises pluripotent cells; the phenomenon that gives rise to the multiplication and maturation of the precursor or primordial cells of blood cells. It is commonly treated with immunosuppressive therapy and/or halogenic bone marrow transplantation. However, despite the comorbidities of aplastic anemia, studies associating physiological changes related to regular physical exercise are still scarce, possibly due to the low prevalence of the disease. Thus, we describe here the impact of a resistance training program on different hematological markers in a patient with severe aplastic anemia. A 39-year-old white male diagnosed with aplastic anemia 22 years ago underwent 12 weeks of resistance training. Different hematological markers were analyzed before and after 7 and 12 weeks of intervention. After the intervention an increase in reticulocytes and several other blood components were observed, the values of which remained within normal limits. In addition, there was a reduction in transaminases and liver enzymes that mark canalicular lesions, proving an improved liver condition. We conclude that after 12 weeks of strength training the patient presented positive changes in different hematological markers, such as erythrocytes, hemoglobin, hematocrit, neutrophils, and leukocytes, suggesting a positive effect of resistance training on the patient's clinical picture associated with the natural course of disease treatment.

Dynamic Response and Running Safety of High-Speed Railway Train–Track–Bridge System Under Near-Fault Pulse-Type Ground Motion

The pulse effect of near-fault ground motion has asevere threat to high-speed railway train running on bridge. Current research generally relies on numerical simulation and lacks physical test data. In this paper, a scale indoor physical test of high-speed train running on bridge is conducted and dynamic characteristics of high-speed railway train–track–bridge system under near-fault pulse-type ground motion are explored. The bridge of the physical test is excited by shaking table with lateral inputs of near-fault pulse-type ground motion, pulse-free ground motion and far-field ground motion. A corresponding numerical model is established and validated by the test data. Then, the influence regularities of pulse effect on system dynamic response and running safety indexes are explored under different peak ground acceleration (PGA) and train speeds using data of the physical tests and the numerical simulation comprehensively. Results suggest that compared to the near-fault pulse-free ground motion and the far-field ground motion, the near-fault pulse-type ground motion leads to larger lateral beam displacement, lateral train acceleration, and running safety indexes in different degrees. And from the data results of this paper, its lateral wheel–rail force and derailment coefficient are the first to break through the limit values. By studying the parameter sensitivity of lateral train acceleration, it was found that under the near-fault pulse-type ground motion, the lateral train acceleration is significantly more sensitive to changes of train speed and PGA. From the perspective of energy, the near-fault pulse-type ground motion results in spectrum intensity (SI) indexes which are larger and improve faster with the increase of PGA than other ground motions. This indicates that it inputs significantly more energy into the high-speed railway train–track–bridge system, although it may not excite larger lateral beam acceleration.

Bone marrow metabolism is affected by body weight and response to exercise training varies according to anatomical location.

High body weight is a protective factor against osteoporosis, but obesity also suppresses bone metabolism and whole-body insulin sensitivity. However, the impact of body weight and regular training on bone marrow (BM) glucose metabolism is unclear. We studied the effects of regular exercise training on bone and BM metabolism in monozygotic twin pairs discordant for body weight. We recruited 12 monozygotic twin pairs (mean ± SD age 40.4 ± 4.5 years; body mass index 32.9 ± 7.6, mean difference between co-twins 7.6 kg/m2 ; eight female pairs). Ten pairs completed the 6-month long training intervention. We measured lumbar vertebral and femoral BM insulin-stimulated glucose uptake (GU) using 18 F-FDG positron emission tomography, lumbar spine bone mineral density and bone turnover markers. At baseline, heavier co-twins had higher lumbar vertebral BM GU (p < .001) and lower bone turnover markers (all p < .01) compared with leaner co-twins but there was no significant difference in femoral BM GU, or bone mineral density. Training improved whole-body insulin sensitivity, aerobic capacity (both p < .05) and femoral BM GU (p = .008). The training response in lumbar vertebral BM GU was different between the groups (time × group, p = .02), as GU tended to decrease in heavier co-twins (p = .06) while there was no change in leaner co-twins. In this study, regular exercise training increases femoral BM GU regardless of weight and genetics. Interestingly, lumbar vertebral BM GU is higher in participants with higher body weight, and training counteracts this effect in heavier co-twins even without reduction in weight. These data suggest that BM metabolism is altered by physical activity.

A novel retrofitting strategy for restoring railway masonry arch bridge undergoing failure by settlement due to scouring

Arch is most possibly one of the oldest structural forms used for bridge superstructures, especially for masonry bridges. Masonry arch bridges are the longest serving structural systems among the railway bridge population most of which are still performing well. To preserve our heritage and to utilize these bridges to their maximum capacity, understanding the behavior and assessing the integrity of arch bridges is vital. Proper maintenance of these bridges will improve the service life of these structures instead of rebuilding with new structure. In this paper, failure investigations are carried out on an old railway stone masonry arch bridge which is severely damaged due to heavy floods during the monsoon. Due to excessive scouring of the soil, uneven settlement of the piers occurred leading to cracks in the arch barrel which made the train traffic to be stopped. Immediate measures are taken to prevent the failure of arch by erecting temporary supporting of full arch and cement grouting of the cracks in order to restore the traffic limiting to minimum speed. In order to assess the integrity and performance of the arch bridge span during the movement of train traffic, instrumentation and response measurements are carried out during the passage of trains with supports under arch and also during the removal of the temporary supports. Field measurements indicated that the load carrying capacity of the arch is inadequate without the temporary supports. Analytical studies are carried out to design a novel retrofitting system to maintain the integrity of the structure while performing the permanent strengthening of the arch. Responses are measured after novel retrofitting to assess the efficacy of the proposed system during the passage of train traffic. The proposed retrofitting system is found to be effective in providing adequate integrity to the arch with less intervention to stoppage of traffic and river flow which will also be integral part of the permanent strengthening scheme for the arch span.

Bacillus Calmette-Guérin vaccination as defense against SARS-CoV-2 (BADAS): a randomized controlled trial to protect healthcare workers in the USA by enhanced trained immune responses

BackgroundA large epidemic, such as that observed with SARS-CoV-2, seriously challenges available hospital capacity, and this would be augmented by infection of healthcare workers (HCW). Bacillus Calmette-Guérin (BCG) is a vaccine against tuberculosis, with protective non-specific effects against other respiratory tract infections in vitro and in vivo. Preliminary analyses suggest that regions of the world with existing BCG vaccination programs have lower incidence and mortality from COVID-19. We hypothesize that BCG vaccination can reduce SARS-CoV-2 infection and disease severity.MethodsThis will be a placebo-controlled adaptive multi-center randomized controlled trial. A total of 1800 individuals considered to be at high risk, including those with comorbidities (hypertension, diabetes, obesity, reactive airway disease, smokers), racial and ethnic minorities, elderly, teachers, police, restaurant wait-staff, delivery personnel, health care workers who are defined as personnel working in a healthcare setting, at a hospital, medical center or clinic (veterinary, dental, ophthalmology), and first responders (paramedics, firefighters, or law enforcement), will be randomly assigned to two treatment groups. The treatment groups will receive intradermal administration of BCG vaccine or placebo (saline) with groups at a 1:1 ratio. Individuals will be tracked for evidence of SARS-CoV-2 infection and severity as well as obtaining whole blood to track immunological markers, and a sub-study will include cognitive function and brain imaging. The majority of individuals will be followed for 6 months, with an option to extend for another 6 months, and the cognitive sub-study duration is 2 years. We will plot Kaplan-Meier curves that will be plotted comparing groups and hazard ratios and p-values reported using Cox proportional hazard models.DiscussionIt is expected this trial will allow evaluation of the effects of BCG vaccination at a population level in high-risk healthcare individuals through a mitigated clinical course of SARS-CoV-2 infection and inform policy making during the ongoing epidemic.Trial registrationClinicalTrials.gov NCT04348370. Registered on April 16, 2020.