Effects of Game Pitch Count and Body Mass Index on Pitching Biomechanics in 9- to 10-Year-Old Baseball Athletes

Background: Pitching while fatigued and body composition may increase the injury risk in youth and adult pitchers. However, the relationships between game pitch count, biomechanics, and body composition have not been reported for a study group restricted to 9- to 10-year-old athletes. Hypothesis: During a simulated game with 9- to 10-year-old athletes, (1) participants will experience biomechanical signs of fatigue, and (2) shoulder and elbow kinetics will correlate with body mass index (BMI). Study Design: Descriptive laboratory study. Methods: Thirteen 9- to 10-year-old youth baseball players pitched a simulated game (75 pitches). Range of motion and muscular output tests were conducted before and after the simulated game to quantify fatigue. Kinematic parameters at foot contact, maximum external rotation, and maximum internal rotation velocity (MIRV), as well as maximum shoulder and elbow kinetics between foot contact and MIRV were compared at pitches 1-5, 34-38, and 71-75. Multivariate analyses of variance were used to test the first hypothesis, and linear regressions were used to test the second hypothesis. Results: MIRV increased from pitches 1-5 to 71-75 (P = .007), and head flexion at MIRV decreased from pitches 1-5 to 34-38 (P = .022). Maximum shoulder horizontal adduction, external rotation, and internal rotation torques increased from pitches 34-38 to 71-75 (P = .031, .023, and .021, respectively). Shoulder compression force increased from pitches 1-5 to 71-75 (P = .011). Correlations of joint torque/force with BMI were found at every pitch period: for example, shoulder internal rotation (R2 = 0.93, P \u3c .001) and elbow varus (R2 = 0.57, P = .003) torques at pitches 1-5. Conclusion: Several results differed from those of previous studies with adult pitchers: (1) pitch speed remained steady, (2) shoulder MIRV increased, and (3) shoulder kinetics increased during a simulated game. The strong correlations between joint kinetics and BMI reinforce previous findings that select body composition measures may be correlated with pitching arm joint kinetics for youth baseball pitchers. Clinical Relevance: The results improve our understanding of pitching biomechanics for 9- to 10-year-old baseball pitchers and may be used in future studies to improve evidence-based injury prevention guidelines

Effects of Game Pitch Count and Body Mass Index on Pitching Biomechanics in 9-to 10-Year-Old Baseball Athletes

Background: Pitching while fatigued and body composition may increase the injury risk in youth and adult pitchers. However, the relationships between game pitch count, biomechanics, and body composition have not been reported for a study group restricted to 9-to 10-year-old athletes. Hypothesis: During a simulated game with 9-to 10-year-old athletes, (1) participants will experience biomechanical signs of fatigue, and (2) shoulder and elbow kinetics will correlate with body mass index (BMI). Study Design: Descriptive laboratory study. Methods: Thirteen 9-to 10-year-old youth baseball players pitched a simulated game (75 pitches). Range of motion and muscular output tests were conducted before and after the simulated game to quantify fatigue. Kinematic parameters at foot contact, maximum external rotation, and maximum internal rotation velocity (MIRV), as well as maximum shoulder and elbow kinetics between foot contact and MIRV were compared at pitches 1-5, 34-38, and 71-75. Multivariate analyses of variance were used to test the first hypothesis, and linear regressions were used to test the second hypothesis. Results: MIRV increased from pitches 1-5 to 71-75 (P ¼.007), and head flexion at MIRV decreased from pitches 1-5 to 34-38 (P ¼ .022). Maximum shoulder horizontal adduction, external rotation, and internal rotation torques increased from pitches 34-38 to 7175 (P ¼.031, .023, and .021, respectively). Shoulder compression force increased from pitches 1-5 to 71-75 (P ¼.011). Correlations of joint torque/force with BMI were found at every pitch period: for example, shoulder internal rotation (R2 ¼0.93, P \u3c .001) and elbow varus (R2 ¼0.57, P ¼.003) torques at pitches 1-5. Conclusion: Several results differed from those of previous studies with adult pitchers: (1) pitch speed remained steady, (2) shoulder MIRV increased, and (3) shoulder kinetics increased during a simulated game. The strong correlations between joint kinetics and BMI reinforce previous findings that select body composition measures may be correlated with pitching arm joint kinetics for youth baseball pitchers. Clinical Relevance: The results improve our understanding of pitching biomechanics for 9-to 10-year-old baseball pitchers and may be used in future studies to improve evidence-based injury prevention guidelines

The structural properties of sexual fantasies for sexual offenders : a preliminary model

While the phenomenon of sexual fantasy has been researched extensively, little contemporary inquiry has investigated the structural properties of sexual fantasy within the context of sexual offending. In this study, a qualitative analysis was used to develop a descriptive model of the phenomena of sexual fantasy during the offence process. Twenty-four adult males convicted of sexual offences provided detailed retrospective descriptions of their thoughts, emotions and behaviours—before, during and after their offences. A data-driven approach to model development, known as Grounded Theory, was undertaken to analyse the interview transcripts. A model was developed to elucidate the structural properties of sexual fantasy in the process of sexual offending, as well as the physiological and psychological variables associated with it. The Sexual Fantasy Structural Properties Model (SFSPM) comprises eight categories that describe various properties of sexual fantasy across the offence process. These categories are: origin, context, trigger, perceptual modality, clarity, motion, intensity and emotion. The strengths of the SFSPM are discussed and its clinical implications are reviewed. Finally, the limitations of the study are presented and future research directions discussed

ML-based Real-Time Control at the Edge: An Approach Using hls4ml

This study focuses on implementing a real-time control system for a particle accelerator facility that performs high energy physics experiments. A critical operating parameter in this facility is beam loss, which is the fraction of particles deviating from the accelerated proton beam into a cascade of secondary particles. Accelerators employ a large number of sensors to monitor beam loss. The data from these sensors is monitored by human operators who predict the relative contribution of different sub-systems to the beam loss. Using this information, they engage control interventions. In this paper, we present a controller to track this phenomenon in real-time using edge-Machine Learning (ML) and support control with low latency and high accuracy. We implemented this system on an Intel Arria 10 SoC. Optimizations at the algorithm, high-level synthesis, and interface levels to improve latency and resource usage are presented. Our design implements a neural network, which can predict the main source of beam loss (between two possible causes) at speeds up to 575 frames per second (fps) (average latency of 1.74 ms). The practical deployed system is required to operate at 320 fps, with a 3ms latency requirement, which has been met by our design successfully

Hypermethioninaemia due to methionine adenosyltransferase I/III (MAT I/III) deficiency: diagnosis in an expanded neonatal screening programme

The Expanded Newborn Screening Program (MS/MS) in the region of Galicia (NW Spain) was initiated in 2000 and includes the measurement of methionine levels in dried blood spots. Between June 2000 and June 2007, 140 818 newborns were analysed, and six cases of persistent hypermethioninaemia were detected: one homocystinuria due to cystathionine β-synthase (CβS) deficiency, and five methionine adenosyltransferase I/III (MAT I/III) deficiencies. The five cases of MAT I/III deficiency represent an incidence of 1/28 163 newborns. In these five patients, methionine levels in dried blood spots ranged from 50 to 147 μmol/L. At confirmation of the persistence of the hypermethioninaemia in a subsequent plasma sample, plasma methionine concentrations were moderately elevated in 4 of the 5 patients (mean 256 μmol/L), while total homocysteine (tHcy) was normal; the remaining patient showed plasma methionine of 573 μmol/L and tHcy of 22.8 μmol/L. All five patients were heterozygous for the same dominant mutation, R264H in the MAT1A gene. With a diet not exceeding recommended protein requirements for their age, all patients maintained methionine levels below 300 μmol/L. Currently, with a mean of 2.5 years since diagnosis, the patients are asymptomatic and show developmental quotients within the normal range. Our results show a rather high frequency of hypermethioninaemia due to MAT I/III deficiency in the Galician neonatal population, indicating a need for further studies to evaluate the impact of persistent isolated hypermethioninaemia in neonatal screening programmes

De-Novo Assembly and Analysis of the Heterozygous Triploid Genome of the Wine Spoilage Yeast Dekkera bruxellensis AWRI1499

Despite its industrial importance, the yeast species Dekkera (Brettanomyces) bruxellensis has remained poorly understood at the genetic level. In this study we describe whole genome sequencing and analysis for a prevalent wine spoilage strain, AWRI1499. The 12.7 Mb assembly, consisting of 324 contigs in 99 scaffolds (super-contigs) at 26-fold coverage, exhibits a relatively high density of single nucleotide polymorphisms (SNPs). Haplotype sampling for 1.2% of open reading frames suggested that the D. bruxellensis AWRI1499 genome is comprised of a moderately heterozygous diploid genome, in combination with a divergent haploid genome. Gene content analysis revealed enrichment in membrane proteins, particularly transporters, along with oxidoreductase enzymes. Availability of this assembly and annotation provides a resource for further investigation of genomic organization in this species, and functional characterization of genes that may confer important phenotypic traits

An ultra-deep sequencing strategy to detect sub-clonal TP53 mutations in presentation chronic lymphocytic leukemia cases using multiple polymerases

Chronic lymphocytic leukaemia (CLL) is the most common clonal B-cell disorder characterized by clonal diversity, a relapsing and remitting course, and in its aggressive forms remains largely incurable. Current front-line regimes include agents such as fludarabine, which act primarily via the DNA damage response pathway. Key to this is the transcription factor p53. Mutations in the TP53 gene, altering p53 functionality, are associated with genetic instability, and are present in aggressive CLL. Furthermore, the emergence of clonal TP53 mutations in relapsed CLL, refractory to DNA-damaging therapy, suggests that accurate detection of sub-clonal TP53 mutations prior to and during treatment may be indicative of early relapse. In this study, we describe a novel deep sequencing workflow using multiple polymerases to generate sequencing libraries (MuPol-Seq), facilitating accurate detection of TP53 mutations at a frequency as low as 0.3%, in presentation CLL cases tested. As these mutations were mostly clustered within the regions of TP53 encoding DNA-binding domains, essential for DNA contact and structural architecture, they are likely to be of prognostic relevance in disease progression. The workflow described here has the potential to be implemented routinely to identify rare mutations across a range of diseases

The structure of the C-terminal actin-binding domain of talin

Talin is a large dimeric protein that couples integrins to cytoskeletal actin. Here, we report the structure of the C-terminal actin-binding domain of talin, the core of which is a five-helix bundle linked to a C-terminal helix responsible for dimerisation. The NMR structure of the bundle reveals a conserved surface-exposed hydrophobic patch surrounded by positively charged groups. We have mapped the actin-binding site to this surface and shown that helix 1 on the opposite side of the bundle negatively regulates actin binding. The crystal structure of the dimerisation helix reveals an antiparallel coiled-coil with conserved residues clustered on the solvent-exposed face. Mutagenesis shows that dimerisation is essential for filamentous actin (F-actin) binding and indicates that the dimerisation helix itself contributes to binding. We have used these structures together with small angle X-ray scattering to derive a model of the entire domain. Electron microscopy provides direct evidence for binding of the dimer to F-actin and indicates that it binds to three monomers along the long-pitch helix of the actin filament

Protein coalitions in a core mammalian biochemical network linked by rapidly evolving proteins

<p>Abstract</p> <p>Background</p> <p>Cellular ATP levels are generated by glucose-stimulated mitochondrial metabolism and determine metabolic responses, such as glucose-stimulated insulin secretion (GSIS) from the β-cells of pancreatic islets. We describe an analysis of the evolutionary processes affecting the core enzymes involved in glucose-stimulated insulin secretion in mammals. The proteins involved in this system belong to ancient enzymatic pathways: glycolysis, the TCA cycle and oxidative phosphorylation.</p> <p>Results</p> <p>We identify two sets of proteins, or protein coalitions, in this group of 77 enzymes with distinct evolutionary patterns. Members of the glycolysis, TCA cycle, metabolite transport, pyruvate and NADH shuttles have low rates of protein sequence evolution, as inferred from a human-mouse comparison, and relatively high rates of evolutionary gene duplication. Respiratory chain and glutathione pathway proteins evolve faster, exhibiting lower rates of gene duplication. A small number of proteins in the system evolve significantly faster than co-pathway members and may serve as rapidly evolving adapters, linking groups of co-evolving genes.</p> <p>Conclusions</p> <p>Our results provide insights into the evolution of the involved proteins. We find evidence for two coalitions of proteins and the role of co-adaptation in protein evolution is identified and could be used in future research within a functional context.</p

Variation in dopamine D2 and serotonin 5-HT2A receptor genes is associated with working memory processing and response to treatment with antipsychotics

Dopamine D2 and serotonin 5-HT2A receptors contribute to modulate prefrontal cortical physiology and response to treatment with antipsychotics in schizophrenia. Similarly, functional variation in the genes encoding these receptors is also associated with these phenotypes. In particular, the DRD2 rs1076560 T allele predicts a lower ratio of expression of D2 short/long isoforms, suboptimal working memory processing, and better response to antipsychotic treatment compared with the G allele. Furthermore, the HTR2A T allele is associated with lower 5-HT2A expression, impaired working memory processing, and poorer response to antipsychotics compared with the C allele. Here, we investigated in healthy subjects whether these functional polymorphisms have a combined effect on prefrontal cortical physiology and related cognitive behavior linked to schizophrenia as well as on response to treatment with secondgeneration antipsychotics in patients with schizophrenia. In a total sample of 620 healthy subjects, we found that subjects with the rs1076560 T and rs6314 T alleles have greater fMRI prefrontal activity during working memory. Similar results were obtained within the attentional domain. Also, the concomitant presence of the rs1076560 T/rs6314 T alleles also predicted lower behavioral accuracy during working memory. Moreover, we found that rs1076560 T carrier/rs6314 CC individuals had better responses to antipsychotic treatment in two independent samples of patients with schizophrenia (n¼63 and n¼54, respectively), consistent with the previously reported separate effects of these genotypes. These results indicate that DRD2 and HTR2A genetic variants together modulate physiological prefrontal efficiency during working memory and also modulate the response to antipsychotics. Therefore, these results suggest that further exploration is needed to better understand the clinical consequences of these genotype–phenotype relationships