A decentralized solid compound storage facility managed by a centralized electronic platform at a growing drug discovery company.

Within a growing drug discovery company, scientists acquire (either through in house synthesis or purchase) then store, retrieve, and ship solid compound samples daily between multiple locations. The efficient management and tracking of this entire process to support drug discovery is a significant challenge. This article describes a decentralized and cost-effective inventory facility that simplifies the solid compound storage and retrieval process. Standardized storage cabinets from the market are utilized, providing a cost-effective physical infrastructure. The cabinets can be distributed across storage rooms at multiple sites and arranged into spaces with a variety of dimensions, allowing the system to be retrofitted into existing facilities and scaled up easily. We can provide storage close to work areas at each location, minimizing both unnecessary movement of staff and transportation of substances. We have applied a systematic barcoding method to the compound batch identifier that correlates with its compound location. This simplifies the compound registration process as well as the process of finding and returning compounds. Additionally, a centralized electronic platform has been employed to store, update and track solid compound information, such as properties, location and quantity. Compound shipment may be initiated from different sites, and a centralized electronic platform assists the information retrieval process, ensuring each location possesses up-to-date information. The electronic platform we present streamlines the management of compound registration, location tracking, weight updates and shipment information, facilitating seamless record sharing among all stakeholders. Every step of the process can be tracked in real time by the project team. The platform can be flexibly configured to adapt to an evolving set of storage locations, with all information and processes being audited.

Skill acquisition interventions for the learning of sports-related skills: A scoping review of randomised controlled trials.

BACKGROUND: Skill acquisition science is the study of how motor skills are acquired, developed and/or learned. There is substantive evidence for general motor skill acquisition in controlled laboratory settings yet the literature on the learning of sports-related skills is typically less conclusive. OBJECTIVES: This scoping review aimed to summarise the current literature on skill acquisition intervention studies examining the learning of sports-related skills as part of a randomised controlled trial, by synthesizing and extracting the most relevant features. METHODS: Four electronic databases (PsychINFO, PubMed, SPORTDiscus and Web of Science) were searched for relevant studies. The sample characteristics of these studies were extracted, and summarised. Two systematic searches of the literature were conducted. In the first search, eighty-six studies were retained. A second search was conducted in July 2022 to include new studies and specifically focused on the inclusion of within-subject design studies, resulting in the inclusion of 35 additional studies. A third search was conducted in May 2023 to include new studies resulting in the inclusion of 10 additional studies. RESULTS: One hundred and thirty studies across 29 sports were included in the review. The vast majority of the studies in this scoping review (n = 104) examined the learning of a sport-related skill in participants with no experience. Twenty-eight percent of all retained studies (n = 35) considered only the learning of a golf skill, and all studies were practiced in a laboratory environment, examining closed motor skills (n = 130). The most common intervention categories reported were attention (n = 22), instruction and demonstration (n = 20), practice design (n = 20), and perceptual training (n = 19). Nearly half of all studies used an immediate retention test within 48 h of the cessation of practice (n = 63), and just over one quarter of studies (n = 34) reported incorporating some form of transfer test. Eighty-six percent (n = 112) reported positive findings. CONCLUSIONS: The skewed focus on golf skills across a small number of skill acquisition interventions, the inconsistent use and reporting of performance measures, practice durations and measures of learning alongside the relatively small sample sizes consisting mostly of inexperienced learners and the skewed publication of positive findings should warrant caution. More empirical studies across a broader range of sports and with more consistent methodologies are needed to develop a robust pool of literature that can support academics and practitioners interested in which skill acquisition interventions could be used to influence the learning of sports-related skills.

Safety and efficacy of peripheral nerve blocks to treat refractory headaches after aneurysmal subarachnoid hemorrhage - A pilot observational study.

Objectives: Headache after aneurysmal subarachnoid hemorrhage (HASH) is common, severe, and often refractory to conventional treatments. Current treatment standards include medications including opioids, until the pain is mitigated. Peripheral nerve blocks (PNBs) may be an effective therapeutic option for HASH. We conducted a small before-and-after study of PNBs to determine safety, feasibility, and efficacy in treatment of HASH. Methods: We conducted a pilot before-and-after observational study and collected data for 5 patients in a retrospective control group and 5 patients in a prospective intervention PNB group over a 12-month period. All patients received a standard treatment of medications including acetaminophen, magnesium, gabapentin, dexamethasone and anti-spasmodics or anti-emetics as needed. Patients in the intervention group received bilateral greater occipital, lesser occipital, and supraorbital PNBs in addition to medications. The primary outcome was pain severity, measured by Numeric pain rating scale (NPRS). All patients were followed for 1 week following enrollment. Results: The mean ages in the PNB group and control group were 58.6 and 57.4, respectively. One patient in the control group developed radiographic vasospasm. Three patients in both groups had radiographic hydrocephalus and IVH, requiring external ventricular drain (EVD) placement. The PNB group had an average reduction in mean raw pain score of 2.76 (4.68, 1.92 p = 0.024), and relative pain score by 0.26 (0.48, 0.22 p = 0.026), compared to the control group. The reduction occurred immediately after PNB administration. Conclusion: PNB can be a safe, feasible and effective treatment modality for HASH. Further investigations with a larger sample size are warranted.

Dynamical biomarkers in teams and other multiagent systems.

Effective team behavior in high-performance environments such as in sport and the military requires individual team members to efficiently perceive the unfolding task events, predict the actions and action intents of the other team members, and plan and execute their own actions to simultaneously accomplish individual and collective goals. To enhance team performance through effective cooperation, it is crucial to measure the situation awareness and dynamics of each team member and how they collectively impact the team's functioning. Further, to be practically useful for real-life settings, such measures must be easily obtainable from existing sensors. This paper presents several methodologies that can be used on positional and movement acceleration data of team members to quantify and/or predict team performance, assess situation awareness, and to help identify task-relevant information to support individual decision-making. Given the limited reporting of these methods within military cohorts, these methodologies are described using examples from team sports and teams training in virtual environments, with discussion as to how they can be applied to real-world military teams.

The prevalence of relative age effects and the influence of the talent pool size on Australian male and female youth football.

The current study explored the association between talent pool size and relative age effects in Football Australia's talent pathway. It also compared relative age effects between male and female players. Participants were 54,207 youth football players (females: n = 12,527, age-range = 14.0-15.9; males: n = 41,680, age-range = 13.0-14.9) eligible for the National Youth Championships. We developed linear regression models to examine the association between the member federation size and the probability of a player being born earlier in the year. We also analysed selection probabilities based on birth quartile and year half across three layers. Overall, talent pool size was associated with a higher probability of selecting a player born in the first half of the year over the second. More specifically, an increase of 760 players led to a 1% higher selection probability for those born in the first six months of a chronological age group. In addition, there were more occurrences of relative age effects in the male than the female sample. Future studies should focus on the impact of the talent pool size on relative age effects at each major talent identification/selection stage of a talent pathway.

CTP Synthase 1 Is a Novel Therapeutic Target in Lymphoma.

Lymphoma is the most common hematological malignancy and is among the 10 most prevalent cancers worldwide. Although survival has been improved by modern immunochemotherapeutic regimens, there remains a significant need for novel targeted agents to treat both B-cell and T-cell malignancies. Cytidine triphosphate synthase 1 (CTPS1), which catalyzes the rate-limiting step in pyrimidine synthesis, plays an essential and nonredundant role in B-cell and T-cell proliferation but is complemented by the homologous CTPS2 isoform outside the hemopoietic system. This report describes the identification and characterization of CTPS1 as a novel target in B- and T-cell cancers. A series of small molecules have been developed which show potent and highly selective inhibition of CTPS1. Site-directed mutagenesis studies identified the adenosine triphosphate pocket of CTPS1 as the binding site for this small molecule series. In preclinical studies, a potent and highly selective small molecule inhibitor of CTPS1 blocked the in vitro proliferation of human neoplastic cells, showing the highest potency against lymphoid neoplasms. Importantly, pharmacological CTPS1 inhibition induced cell death by apoptosis in the majority of lymphoid cell lines tested, thus demonstrating a cytotoxic mechanism of action. Selective CTPS1 inhibition also inhibited the growth of neoplastic human B- and T- cells in vivo. These findings identify CTPS1 as a novel therapeutic target in lymphoid malignancy. A compound from this series is in phase 1/2 clinical studies for the treatment of relapsed/refractory B- and T-cell lymphoma (NCT05463263).

Development and Validation of Single Items for Fatigue and Recovery in Dancers.

PURPOSE: To examine the construct validity and reliability of 2 single items for fatigue and recovery in dancers. The construct validity was assessed using reference instruments: the fatigue items of the Brunel Mood Scale (BRUMS) and the Short Recovery and Stress Scale (SRSS). A secondary aim was to explore the respondent interpretation of these 2 items using a concept identification approach. METHODS: Two hundred forty-three (N = 243) dancers completed single-item fatigue and recovery (unipolar and bipolar), BRUMS, and SRSS once for construct validity. For reliability, 49 dancers completed the questionnaires twice, 1 week apart. Using a concept identification approach, 49 dancers were also asked comprehension and interpretation of fatigue and recovery. RESULTS: The fatigue item correlated with SRSS stress items (rs = .37-.51) and BRUMs fatigue items (rs = .63-.66). The recovery item was only partially confirmed in terms of construct validity, when using the SRSS recovery items as reference (rs = .39-.43). Reliability was confirmed for the single items of fatigue (κ = .77-.78) and recovery (κ = .71-.78). Main responses for the concept of fatigue were tiredness (34.7%), muscle soreness (17.3%), and energy (13.0%). Main responses for the concept of recovery were muscle soreness (43.0%), tiredness (27.9%), and fatigue (24.0%). CONCLUSION: We provide preliminary confirmation of the validity and reliability of the single item fatigue in dancers. The recovery item was only partially confirmed in terms of construct validity, when using the SRSS recovery items as reference, but did display acceptable reliability and agreement. Further research is warranted further exploring other measurement properties.

A holistic analysis of collective behaviour and team performance in Australian Football via structural equation modelling.

Despite awareness of the importance of quantifying technical, tactical, and physical characteristics of match play, few studies have examined the structural relationship of these aspects in professional sport. Accordingly, this study concurrently examined these components in relation to quarter outcome (n = 272) in Australian Football. The study followed a retrospective longitudinal case study design where one teams' cooperative passing network, skill counts, physical loads, and spatiotemporal behaviours during official Australian Football League games were collected from a period spanning four seasons (2016-2019). A principal components analysis (PCA) and structural equation modelling were used to explore the structural relationships between components and examine the influence on quarter outcome as determined by the point differential (quarter margin). Scoring opportunity and ball movement had direct associations with quarter margin, while unpredictability, uncontested behaviour and physical behaviour did not. Negative associations between uncontested behaviour and scoring opportunity suggest that elevated high-pressure success and a lack of synchrony may positively influence scoring opportunity, a determinant of quarter margin. Further, negative associations between physical behaviour and ball movement suggest that with less physical work, a team's collective ability to transfer possession between teammates is facilitated, offering an interesting dichotomy between skill and physical demands of Australian Football. While hundreds of different metrics are available, the present study was the first to concurrently examine the influence of a variety of match play components on performance outcomes in Australian Football. These results may provide direction for coaches and practitioners when contemplating practice design, tactical strategies, or the development of behaviour through specific training exercises. Game plans and training drills that focus on optimising attacking and low-pressure ball movement coupled with high levels of mutual interaction between teammates may be beneficial for performance.

Factors associated with cooperative network connectedness in a professional Australian football small-sided game.

OBJECTIVES: Connectedness is a cooperative network measure that describes how well players in the team bi-directionally connect and how easily reachable they are to other players. It has been associated with an increased probability of winning competitive matches in professional Australian Football (AF), although applications towards training have not been reported. Therefore, this study investigated associations between constraints manipulated by professional AF coaches and the connectedness of cooperative passing networks during a small-sided game (SSG). DESIGN: Data were collected describing the task constraints manipulated by professional coaches across one SSG performed on multiple occasions. The SSG focused on transitioning between defence and attack and was performed fifteen times across a whole season, resulting in 36 observations of team connectedness. METHOD: A linear mixed-effects model was constructed to examine the collective influence of constraints manipulations made by professional coaches (e.g. field size) and team skill characteristics (e.g. kick efficiency) on connectedness scores. RESULTS: The number of team shots on goal and the time on task both positively contributed to connectedness scores, explaining 65% of its variance. CONCLUSION: The findings show that the number of shots on goal and the time on task may be used to elicit higher or lower connectedness scores in AF SSGs. Skill acquisition specialists, in conjunction with coaching staff, can use these metrics to aid practice design in professional AF or indeed other invasion-style team sports.

Discovery and Optimization of Potent and Orally Available CTP Synthetase Inhibitors for Use in Treatment of Diseases Driven by Aberrant Immune Cell Proliferation.

Herein, we report the discovery of a first-in-class chemotype 2-(alkylsulfonamido)thiazol-4-yl)acetamides that act as pan-selective inhibitors of cytidine 5'-triphosphate synthetase (CTPS1/2), critical enzymes in the de novo pyrimidine synthesis pathway. Weak inhibitors identified from a high-throughput screening of 240K compounds have been optimized to a potent, orally active agent, compound 27, which has shown significant pharmacological responses at 10 mg/kg dose BID in a well-established animal model of inflammation.

Tactical analysis of individual and team behaviour in professional Australian Football.

INTRODUCTION: This study sought to reduce the dimensionality of commonly reported spatiotemporal characteristics obtained from Australian Football games to facilitate their practical use and interpretability. METHODS: A retrospective longitudinal design was utilised with team and individual spatiotemporal variables, measured via global navigation satellite system devices, collected during official Australian Football League matched over three seasons. Two separate principal component analyses were conducted at the team and individual level to reduce correlated spatiotemporal characteristics into a smaller set of uncorrelated components. RESULTS: At the team level, eighteen variables were reduced to five components pertaining to dispersive coordination, lateral predictability and spacing, multidirectional synchrony, longitudinal predictability and longitudinal behaviour whilst maintaining 69% of variance in the original dataset. At the individual level, fifteen variables were reduced to four components pertaining to multidirectional and spacing synchrony, unpredictability, player movement and player positioning whilst maintaining 64% of variance. CONCLUSION: This study is the first to provide a simplified, novel method for analysing spatiotemporal behaviour in an Australian Football context with both the team- and individual- derived metrics revealing useful information for coaches and practitioners. Components may provide insight into behaviours that emerge and persist throughout a game and allow coaches to distinguish between different playing/behavioural styles.

An efficient and reliable chemical inventory system at a growing drug discovery company.

Within a growing drug discovery company, hundreds of scientists take and move reagent chemicals on a daily basis. Conveniently updating the locations of tens of thousands of chemical containers in an electronic system is a big challenge. We have an electronic inventory system, but keeping the chemical records up to date relied on scientists finding an available computer in the lab and logging into a system whenever they took or moved a chemical container, taking several minutes. It was all too easy to think that the task could be deferred until later, but the scientist may then forget all about it, leaving the database inaccurate. As a result, searching for the chemicals we need can take a frustratingly long time if they are not where they should be. We have developed an efficient and reliable system, namely ScanStation, to solve this issue. It relies on a low-cost Raspberry Pi attached to a touch screen connected with a barcode scanner. This equipment is always on and placed in strategic locations around all our labs and chemical stores. This new process is much easier. There is no need to remove gloves to log into the computer, and it is just a scan on the barcode and is done. Now when we check the database for a chemical, we get an instant answer that reliably tells us where to find it. All the time we save have a real benefit in our productivity and our scientists can focus on discovering new medicines.

Match simulation practice may not represent competitive match play in professional Australian football.

Match simulation in team sport should sample representative constraints and behaviours to those observed in competitive matches to enhance near skill transfer. This study compared task constraints (field length, field width, length per width ratio, space per player), time-standardised skill metrics (goals, shots on goal, handballs, kicks, marks, turnovers, tackles, handball proficiency, kick proficiency) and cooperative passing metrics (connectedness, indegree variability and outdegree variability) between match simulation practice and competitive Australian Football League (AFL) games for one professional team. MANOVAs identified activity-related differences for task constraints, skill metrics and cooperative passing networks. During match simulation, goals were scored more frequently, but with less passing actions per minute. Receiving and distributing passing networks were more centralised (reliance on fewer key individuals), with less turnovers and tackles per minute compared to AFL matches. If match simulation is designed to reflect competition, then player and team skill preparation may be compromised. Furthermore, the competing demands in high-performance sport may restrict the degree of representativeness that can be achieved during practice. These findings provide valuable insight and may assist practitioners and/or coaches to understand the value of match simulation practice and to maximise near skill transfer from match simulation to competition.

Implementation of path analysis and piecewise structural equation modelling to improve the interpretation of key performance indicators in team sports: An example in professional rugby union.

Analysis of key performance indicators (KPIs) in team sports has frequently involved multiple univariate analyses and modelling of direct associations between each KPI and match outcomes. This study aimed to show a more appropriate framework and modelling process to establish causal plausibility for future confirmatory studies. A cross-sectional design was adopted, using 337 team-match observations of Australian Super Rugby performances. A tentative model was developed in consultation with a domain expert (national analyst) and analysed using piecewise structural equation modelling. Model fit was assessed using Fisher's C and the Akaike Information Criterion (AIC). Hypothesised relationships were modelled using linear mixed effects models and unmodelled pathways were investigated using tests of directed separation. The model was an acceptable fit overall, and adjustments were identified in collaboration with the national head analyst, improving the AIC from 127.15 to 120.77 (Fisher's C = 66.78; p = 0.382). Modelling the hierarchical data structure and developing models that contain more logical hypothesised associations (in consultation with domain experts) is a more useful and important step to analyse and interpret effects of KPIs on team performance. This analysis provides support to the plausibility of the causal structure and generation of new and more precise hypotheses.

An assessment of physical and spatiotemporal behaviour during different phases of match play in professional Australian football.

Despite advancements in the scale of data available for quantifying the physical and spatiotemporal characteristics of match play, there is an absence of research combining these aspects in professional sport. This study sought to differentiate between phases of play in professional Australian football using novel physical and spatiotemporal metrics. Data was obtained from Australian Football League games to provide new insight into the specific characteristics of each phase of play. A retrospective cross-sectional design was utilised with team's physical and spatiotemporal variables, measured via global navigation satellite system devices. A multinomial logistic regression was conducted to determine which physical and spatiotemporal measures were associated with each phase of play (contested play, defence, offence, set shot, goal reset, umpire stoppage). The addition of the predictors to a model that contained only the intercept significantly improved the fit between the model and data, with the logistic model correctly predicting the phase of play for 63.7% of the cases. This was the first study to concurrently examine differences in physical and spatiotemporal characteristics with respect to phase of play in an Australian football context. Differences in duration, physical and spatiotemporal properties were observed, providing new insight for coaches and subsequently providing direction for conditioning and practice design.

Analysis of the worst-case scenarios in an elite football team: Towards a better understanding and application.

This study investigated the variability in the worst-case scenario (WCS) and suggested a framework to improve the definition and guide further investigation. Optical tracking data from 26 male players across 38 matches were analysed to determine the WCS for total distance, high-speed running (>5.5 m.s-1) and sprinting (>7.0 m.s-1) using a 3-minute rolling window. Position, total output, previous epoch, match half, time of occurrence, classification of starter vs substitute, and minutes played were modelled as selected contextual factors hypothesized to have associations with the WCS. Linear mixed effects models were used to account for cross-sectional observations and repeated measures. Unexplained variance remained high (total distance R2 = 0.53, high-speed running R2 = 0.53 and sprinting R2 = 0.40). Intra-individual variability was also high (total distance CV = 4.6-8.2%; high-speed CV = 15.6-37.8% and Sprinting CV = 21.1-76.4%). The WCS defined as the maximal physical load in a given time-window, produces unstable metrics lacking context, with high variability. Furthermore, training drills targetting this metric concurrently across players may not have representative designs and may underprepare athletes for complete match demands and multifaceted WCS scenarios. Using WCS as benchmarks (reproducing similar physical activity for training purposes) is conceptually questionable.

Additional Clothing Increases Heat Load in Elite Female Rugby Sevens Players.

PURPOSE: To determine whether elite female rugby sevens players are exposed to core temperatures (Tc) during training in the heat that replicate the temperate match demands previously reported and to investigate whether additional clothing worn during a hot training session meaningfully increases the heat load experienced. METHODS: A randomized parallel-group study design was employed, with all players completing the same approximately 70-minute training session (27.5°C-34.8°C wet bulb globe temperature) and wearing a standardized training ensemble (synthetic rugby shorts and training tee [control (CON); n = 8]) or additional clothing (standardized training ensemble plus compression garments and full tracksuit [additional clothing (AC); n = 6]). Groupwise differences in Tc, sweat rate, GPS-measured external locomotive output, rating of perceived exertion, and perceptual thermal load were compared. RESULTS: Mean (P = .006, ηp2=.88) and peak (P < .001, ηp2=.97) Tc were higher in AC compared with CON during the training session. There were no differences in external load (F4,9 = 0.155, P = .956, Wilks Λ = 0.935, ηp2=.06) or sweat rate (P = .054, Cohen d = 1.09). A higher rating of perceived exertion (P = .016, Cohen d = 1.49) was observed in AC compared with CON. No exertional-heat-illness symptomology was reported in either group. CONCLUSIONS: Player Tc is similar between training performed in hot environments and match play in temperate conditions when involved for >6 minutes. Additional clothing is a viable and effective method to increase heat strain in female rugby sevens players without compromising training specificity or external locomotive capacity.

Acute:Chronic Workload Ratio: Conceptual Issues and Fundamental Pitfalls.

The number of studies examining associations between training load and injury has increased exponentially. As a result, many new measures of exposure and training-load-based prognostic factors have been created. The acute:chronic workload ratio (ACWR) is the most popular. However, when recommending the manipulation of a prognostic factor in order to alter the likelihood of an event, one assumes a causal effect. This introduces a series of additional conceptual and methodological considerations that are problematic and should be considered. Because no studies have even tried to estimate causal effects properly, manipulating ACWR in practical settings in order to change injury rates remains a conjecture and an overinterpretation of the available data. Furthermore, there are known issues with the use of ratio data and unrecognized assumptions that negatively affect the ACWR metric for use as a causal prognostic factor. ACWR use in practical settings can lead to inappropriate recommendations, because its causal relation to injury has not been established, it is an inaccurate metric (failing to normalize the numerator by the denominator even when uncoupled), it has a lack of background rationale to support its causal role, it is an ambiguous metric, and it is not consistently and unidirectionally related to injury risk. Conclusion: There is no evidence supporting the use of ACWR in training-load-management systems or for training recommendations aimed at reducing injury risk. The statistical properties of the ratio make the ACWR an inaccurate metric and complicate its interpretation for practical applications. In addition, it adds noise and creates statistical artifacts.

Improving the interpretation of skill indicators in professional Australian Football.

OBJECTIVES: This study aimed to provide a simplified, novel method for analysing technical skill involvements in an Australian Football context by reducing the dimensionality of commonly reported skill counts obtained from Australian Football League (AFL) games. This may facilitate their practical use and interpretability. DESIGN: Retrospective longitudinal design where individual players' technical skill counts were collected over three seasons of official AFL games. METHODS: Seventy-three skill count values provided publicly by ChampionData® were collected for each match over a three-year analysis period. A principal component analysis was used to reduce the dimensionality of a large number of correlated technical skill indicators into a smaller set of uncorrelated components whilst maintaining most of the variance from the original data set. RESULTS: The principal component analysis derived four principal components pertaining to high-pressure success, low-pressure success, attacking ball movement ability and scoring ability. CONCLUSIONS: This study is the first to provide a simplified, novel method for analysing technical skill counts in Australian Football. The derived metrics reveal useful information for coaches and practitioners. This may consequently ease the interpretation of skill count data available to coaches from games, guide opposition analysis, help in the design of representative practice and inform player performance ratings.

Using cooperative networks to analyse behaviour in professional Australian Football.

OBJECTIVES: Reducing the dimensionality of commonly reported complex network characteristics obtained from Australian Football League (AFL) games to facilitate their practical use and interpretability. DESIGN: Retrospective longitudinal design where individual players' interactions, determined through the distribution and receipt of kicks and handballs, during official AFL games were collected over three seasons. METHODS: A principal component analysis was used to reduce the number of characteristics related to the cooperative network analysis. RESULTS: The principal component analysis derived two individual-based principal components pertaining to in- and out-degree importance and three team-based principal components related to connectedness and in- and out-degree centralisation. CONCLUSIONS: This study is the first to provide a simplified, novel method for analysing complex network structures in an Australian Football context with both the team- and individual-derived metrics revealing useful information for coaches and practitioners. This may consequently guide opposition analysis, training implementation, player performance ratings and player selection.