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Purpose: The amount of sodium chloride (NaCl) that escapes a nebulizer cup, intended for patient inhalation, during a 5-min hypertonic saline jet nebulization (HSJN) breathing treatment is apparently unknown in the pure and applied scientific literature. This study aimed to address this void by focusing on NaCl mass changes prior to and after a typical HSJN breathing treatment using an ordinary household, medical-grade air compressor. Research methods: Saline solutions of varying concentrations were nebulized to room air for 5 min. Pre- and post-nebulization NaCl concentrations were determined from measured conductivities via calibration curve. The resulting data were used to quantify NaCl mass changed from the beginning and end of a typical HSJN breathing treatment. Main findings: Conductivity was a reliable metric in NaCl concentrations ranging from 2.10 × 10-1 to 8.16 × 10-3 M. Pre- and post-nebulization NaCl mass differences of 19–114 mg linearly correlated with saline concentration (wt%). The resulting trendline data reasonably predict how much NaCl is available for patient inhalation during a typical HSJN breathing treatment. Linearity in the data suggests that factors such as colligative properties (e.g., osmolarity) have a minimal influence on the amount of NaCl that escapes the nebulizer cup. Conclusions: These results are the first to quantify how much NaCl escapes a nebulizer cup during a typical HSJN breathing treatment. Furthermore, the results represent a key starting point upon which future studies can be built to explore additional airflow rates, kinetics, and temperature effects. Collectively, these findings will play a critical role in ascertaining the mechanism of action in hypertonic saline breathing treatments.

Objectives: The purpose of this study was to estimate between and within-athlete variabilities, to form threshold values for interpreting changes in locomotor activity in a female junior international hockey team., Design: Thirty-three female international hockey players (age: 20 ± 0.9 year; height: 166.1 ± 4.4 cm; body mass: 62.5 ± 6.2 kg) competed in thirty-four junior international hockey games.., Methods: Data were monitored through global positioning system technology. Locomotor activity was quantified as relative distances covered by players for each quarter at three speed zones (<16 km/h, 16-19.9 km/h, >20 km/h). Data were analysed using linear mixed models, accounting for the fixed effects of position (defenders, n = 13; midfielders, n = 8; forwards, n = 12), game result, type, location, and opposition rank. Variabilities are summarised as coefficients of variation (%CV)., Results: Variabilities in athletes' game-to-game and quarter-to-quarter locomotor activity differed substantially between lower (<16 km/h) and higher (16-19.9 km/h and >20 km/h) speed zones. Game-to-game variability of low-speed movement (<16 km/h) was 5%; whereas, corresponding variabilities for high- (16-19.9 kmh) and very high-speed (>20 km/h) running were 22% and 34%, respectively. Within-athlete quarter-to-quarter variability increased for each speed zone, and was greatest for midfielders in low-speed movement and for defenders in high and very high-speed running., Conclusions: The game-to-game variabilities inform thresholds for estimating changes in performance over time. Caution is required when interpreting such data, and coaches should carry out estimates in their specific contexts. Additionally, quarter-to-quarter variabilities in high- and very high-speed running for junior international hockey players outline position specific differences informing training practices to better prepare players for game demands., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Abstract: McGuinness, A, Passmore, D, Malone, S, and Collins, K. Peak running intensity of elite female field hockey players during competitive match play. J Strength Cond Res 36(4): 1064-1070, 2022-In recent years, backroom coaching staff have relied heavily on the global demands of competitive match-play to monitor running performance within training and match environments. Although, these figures help prepare players for the demands of match-play, they do not account for the physical and physiological stress of the most intense periods of competition. The aim of the current study was to quantify the duration and position-specific maximal running performance during match-play using a 1-10-minute moving average epoch methodology. Twenty-six (n = 26) elite international female field hockey players (23 ± 3 years; 162.6 ± 13 cm; 66 ± 6 kg) participated in the current observational study. Data were collected during 22 international games, resulting in over 360 individual samples (n = 368) being obtained for analysis. Players were categorized based on their positional lines of play (defenders, midfielders, and forwards). Variables of interest included relative total (m·min-1), high-speed (>16 km·h-1; m·min-1) and sprint distance (>20 km·h-1; m·min-1). Regardless of position, varying differences were observed between 10-minute rolling average for relative total (mod-large), high-speed (mod-large), and sprint (mod-large) distance respectively. Furthermore, as the duration of the rolling average increased, so did the observed differences (small). The forwards (119.3 ± 19.7 m·min-1) were reported to have the highest peak output during minute one for relative high-speed distance when compared with the defenders (100.7 ± 19.7, effect size [ES] 0.9, large) and the midfield (106.8 ± 23.4 m·min-1, ES 0.5, moderate). The results of the current study show that the running performance of field hockey players alters during match-play irrespective of moving average. Finally, the data will aid practitioners in the development of sport-specific drills to adequately prepare hockey players for the maximal intensity periods of elite hockey match-play., (Copyright © 2020 National Strength and Conditioning Association.)

Existing literature highlights the common characteristics of successful talent development environments, notably the need for long-term development, individual athlete attention, communication, alignment, and psycho-behavioural development. Little is known however about the complex talent development environment of an international sport organisation where multiple contexts and various stakeholders exist. Considering the lack of research relating to females in talent development, we examined a female national hockey talent development environment and more specifically the level of coherence that existed within the talent development environment from different stakeholder perspectives. Twenty-seven international female hockey players and fourteen pathway staff members from across the talent development pathway participated in semi-structured focus groups. An inductive-deductive thematic analysis was conducted. Results suggest that the talent development environment provides a long-term development experience supplemented with individual athlete attention at international level. However, a general lack of coherence and systematic development was evident across the talent development environment contexts with varying levels of coherence found within the higher-order themes of appropriate development, not early success, individualised and ongoing development, and wide-ranging coherent messages and support. This highlights a need for improved direction from the National Governing Body if systematic coherence towards talent development is to be achieved.

Background: Fatigue is one of the most common and debilitating symptoms of multiple sclerosis (MS), experienced by more than 80% of people with MS. FACETS (Fatigue: Applying Cognitive Behavioral and Energy Effectiveness Techniques to Lifestyle) is an evidence-based, face-to-face, 6-session group fatigue management program for people with MS. Homework tasks are an integral part of FACETS and are currently undertaken in a paper-based form. Feedback from a consultation undertaken with FACETS attendees and health care professionals with experience in delivering the FACETS program suggested that being able to complete the homework tasks digitally would be desirable, potentially enhancing engagement and adherence and enabling on-the-go access to fit into busy lifestyles. Relative to other long-term conditions, there are few apps specifically for MS and, of those available, many have been developed with little or no input from people with MS., Objective: The purpose of this mixed methods study was to create a digital toolkit comprising the homework tasks (eg, activity diary, goal planner, thought diary) of the FACETS program for people with MS, considering end users' unique requirements throughout the design, build, prototyping, and testing stages., Methods: Phase 1 involved the elicitation of detailed user requirements for the toolkit via 2 focus groups with previous attendees of FACETS (n=3 and n=6) and wireframing. Phase 2 involved supervised usability testing with people with MS (n=11) with iterative prototyping. The usability sessions involved going through test scenarios using the FACETS toolkit on an Android test phone with video capture and concurrent think-aloud followed by completion of the System Usability Scale (SUS) and a semistructured interview collecting feedback about design, content, and functionality., Results: The mean SUS score for the digital toolkit was 74.3 (SD 16.8, 95% CI 63.2-85.6; range 37.5-95), which equates to an adjective rating of good and a B grade (70th-79th percentile range) on the Sauro-Lewis curved grading scale. A number of usability and design issues (such as simplifying overall screen flow to better meet users' needs) and suggestions for improvements (such as using location-based services and displaying personalized information and progress via a central dashboard) were addressed and implemented during the usability testing cycle., Conclusions: This work highlights the importance of the participation of people with MS across the entire development cycle, working to a human-centered design methodology to enable a considered and MS-centered solution to be developed. Continued horizon scanning for emergent technological enhancements will enable us to identify opportunities for further improvements to the FACETS toolkit prior to launch. The toolkit supports self-monitoring and management of fatigue and has potential applicability to other long-term conditions where fatigue is a significant issue., (©Sarah Thomas, Andy Pulman, Huseyin Dogan, Nan Jiang, David Passmore, Keith Pretty, Beth Fairbanks, Angela Davies Smith, Peter W Thomas. Originally published in JMIR Formative Research (https://formative.jmir.org), 09.12.2021.)

Although there is research available into successful Talent Development Environments (TDEs), the data mostly reflects TDEs in elite academies, national groups or in a single successful club. This literature provides insight into the positive characteristics that are commonplace in these effective TDEs. However, little is known about the TDE surrounding an entire amateur national organization where athletes regularly compete across multiple teams, simultaneously representing at both domestic and international level. Importantly this added complexity increases the number of stakeholders across the pathway (e.g., school, club, international) creating a need for coherence throughout the TDE. Additionally considering the lack of research relating to females in talent development, we were interested from a pragmatic view, in examining the TDE of an amateur national hockey organization where young female athletes must navigate the pathway while simultaneously playing on multiple teams, contending with various coaches and contexts. The results suggest that the TDE provides a long term development experience supplemented with a good support network across all contexts. However, the alignment of expectations across contexts and the quality preparation of athletes in this TDE requires more attention to facilitate effective holistic athlete development.

A series of tetrahydroisoquinoline-based benzodiazepine dimers were synthesized and tested for in vitro cytotoxicity against a panel of cancer cell lines. Structure-activity relationship investigation of various spacers guided by molecular modeling studies helped to identify compounds with picomolar activity. Payload 17 was conjugated to anti-mesothelin and anti-fucosylated monosialotetrahexosylganglioside (FucGM1) antibodies using lysosome-cleavable valine-citrulline dipeptide linkers via heterogeneous lysine conjugation and bacterial transglutaminase-mediated site-specific conjugation. In vitro, these antibody drug conjugates (ADCs) exhibited significant cytotoxic and target-mediated selectivity on human cancer cell lines. The pharmacokinetics and efficacy of these ADCs were further evaluated in gastric and lung cancer xenograft models in mice. Consistent pharmacokinetic profiles, high target specificity, and robust antitumor activity were observed in these models after a single dose of the ADC- 46 (0.02 μmol/kg).

Antibody-drug conjugates (ADCs) use antibodies to deliver cytotoxic payloads directly into tumor cells via specifically binding to the target cell surface antigens. ADCs can enhance the anti-tumor effects of antibodies, and increase the delivery of cytotoxic payloads to cancer cells with a better therapeutic index. An ADC was prepared with a potent carbamate-containing tubulysin analogue attached to an anti-mesothelin antibody via a Cit-Val dipeptide linker. An aniline functionality in the tubulysin analogue was created to provide a site of linker attachment via an amide bond that would be stable in systemic circulation. Upon ADC internalization into antigen-positive cancer cells, the Cit-Val dipeptide linker was cleaved by lysosomal proteases, and the drug was released inside the tumor cells. The naturally occurring acetate of tubulysin was modified to a carbamate to reduce acetate hydrolysis of the ADC in circulation and to increase the hydrophilicity of the drug. The ADC bearing the monoclonal anti-mesothelin antibody and the carbamate-containing tubulysin was highly potent and immunologically specific to H226 human lung carcinoma cells in vitro, and efficacious at well-tolerated doses in a mesothelin-positive OVCAR3 ovarian cancer xenograft mouse model.

Stability of antibody-drug conjugates (ADCs) in mouse serum is one of the critical requirements for the evaluation of ADCs in mouse tumor models. Described herein is a strategy to address the mouse serum instability of uncialamycin linker-payloads through various chemical approaches that involve modification of different parts of the linker and payload. This effort ultimately led to the identification of a m -amide p -aminobenzyl carbamate (MA-PABC) group that resulted in linkers with dramatic improvement of mouse serum stability without affecting the desired proteolytic cleavage., Competing Interests: The authors declare no competing financial interest.

McGuinness, McMahon, G, A, Malone, S, Kenna, D, Passmore, D, and Collins, K. Monitoring wellness, training load, and running performance during a major international female field hockey tournament. J Strength Cond Res 34(8): 2312-2320, 2020-The current observational study quantified players' activity profiles during a major international female field hockey tournament and determined whether an association exists between well-being measures and running performance within elite female hockey players. Elite female field hockey players (23 ± 3 years; 162.6 ± 13 cm; and 66 ± 6 kg) participated in the study. Participants running performance was monitored using global positioning system technology (S5; Catapult Innovations, Scoresby, Victoria, Australia), with daily well-being questionnaires used to quantify player responses during the tournament. Thresholds for the magnitude of the observed change for each variable were determined using the Hopkins Spreadsheets for analysis of controlled trials. Relative distance (m·min) was likely lower when compared with game 1 in game 7. Relative high speed (m·min >16 km·h) was likely lower in games 5, 6, and 7 when compared with game 1. Subjective load was very likely higher in game 2 and very likely lower in game 3 when compared with game 1. Mood and sleep quality were likely lower in game 1 when compared with game 4 and game 7. Muscle soreness was likely higher when compared with game 1 in game 7. During the tournament, it was observed that a decrease in players' daily well-being was accompanied by changes in running performance. Furthermore, changes to players' muscle soreness and sleep quality result in decreased players' high-speed running performance during match-play. Therefore, to prevent the observed effects, coaches should adopt strategies to enhance sleep quality and incorporate specific recovery modalities to reduce musculoskeletal soreness.

Dietary fibre (DF) has multiple health benefits and wheat grains are major sources of DF for human health. However, DF is depleted in white wheat flour which is more widely consumed than wholegrain. The major DF component in white flour is the cell wall polysaccharide arabinoxylan (AX). We have identified the Chinese wheat cultivar Yumai 34 as having unusually high contents of AX in both water-soluble and insoluble forms. We have therefore used populations generated from crosses between Yumai 34 and four other wheat cultivars, three with average contents of AX (Ukrainka, Altigo and Claire) and one also having unusually high AX (Valoris), in order to map QTLs for soluble AX (determined as relative viscosity of aqueous extracts of wholemeal flours) and total AX (determined by enzyme fingerprinting of white flour). A number of QTL were mapped, but most were only detected in one or two crosses. However, all four crosses showed strong QTLs for high RV/total AX on chromosome 1B, with Yumai 34 being the increasing parent, and a KASP marker for the Yumai 34 high AX allele was validated by analysis of high AX lines derived from Yumai 34 but selected by biochemical analysis. A QTL for RV was also mapped on chromosome 6B in Yumai 34 x Valoris, with Valoris being the increasing allele, which is consistent with the observation of transgressive segregation for this population. Association studies in an independent germplasm panel identified marker trait associations for relative viscosity in these same locations while direct selection for fibre content in breeding resulted in high levels of enrichment for the Yumai 34 1B allele. The data therefore indicate that marker-assisted breeding can be used to develop wheat with high AX fibre in white flour., Competing Interests: The authors have declared that no competing interests exist.

Antibody drug conjugates (ADCs) can undergo in vivo biotransformation (e.g., payload metabolism, deconjugation) leading to reduced or complete loss of activity. The location/site of conjugation of payload-linker can have an effect on ADC stability and hence needs to be carefully optimized. Affinity capture LC-MS of intact ADCs or ADC subfragments has been extensively used to evaluate ADC biotransformation. However, the current methods have certain limitations such as the requirement of specific capture reagents, limited mass resolution of low mass change metabolites, low sensitivity, and use of capillary or nanoflow LC-MS. To address these challenges, we developed a generic affinity capture LC-MS assay that can be utilized to evaluate the biotransformation of any site-specific ADC independent of antibody type and site of conjugation (Fab and Fc) in preclinical studies. The method involves a combination of some or all of these steps: (1) "mono capture" or "dual capture" of ADCs from serum with streptavidin magnetic beads coated with a generic biotinylated antihuman capture reagent, (2) "on-bead" digestion with IdeS and/or PNGase F, and (3) reduction of interchain disulfide bonds to generate ∼25 kDa ADC subfragments, which are finally analyzed by LC-HRMS on a TOF mass spectrometer. The advantages of this method are that it can be performed using commercially available generic reagents and requires sample preparation time of less than 7 h. Furthermore, by reducing the size of intact ADC (∼150 kDa) to subfragments (∼25 kDa), the identification of conjugated payload and its metabolites can be achieved with excellent sensitivity and resolution (hydrolysis and other small mass change metabolites). This method was successfully applied to evaluate the in vitro and in vivo biotransformation of ADCs conjugated at different sites (LC, HC-Fab, and HC-Fc) with various classes of payload-linkers.

Background: Fruit and vegetable consumption is important for health, but many individuals fail to consume adequate amounts for health benefits. Although many individuals are aware of current fruit and vegetable consumption recommendations, research suggests that adherence to these is hampered by low knowledge of the details of these recommendations., Objective: This paper reports the development and details of a pilot randomized controlled test of a novel interactive mobile phone app for addressing low knowledge of the UK 5-a-day fruit and vegetable recommendations., Methods: Requirements for the app were first defined by researchers and potential end users and prioritized using the MoSCoW (Must have, Should have, Could have, Won't have) method. Second, a prototype mobile phone app was developed using an agile approach. Third, the prototype app was tested in a randomized controlled pilot trial for impacts on knowledge and intake of fruit and vegetables. Volunteers were randomized to either receive (n=50) or not receive the app (n=44) for 2 or 4 weeks, and fruit and vegetable knowledge, intake, and behavior were assessed at the beginning of the study and after 1 and 2 weeks or after 2 and 4 weeks, respectively. App usage and qualitative feedback were also investigated. All findings then informed the development of a final app., Results: Low knowledge of consumption recommendations centered around portion sizes and the need for variety, and an interactive mobile phone app was considered a suitable tool for improving this knowledge in a practical manner that would be available both at time of consumption and outside of these times. The pilot test revealed improved behavior after 2 weeks compared with baseline in volunteers who received the app, but improvements in knowledge on fruit and vegetable recommendations were found in both groups, and no improvements in fruit and vegetable intakes were found in formal measures. Patterns of app usage and qualitative feedback also suggested a number of modifications. The resultant final app incorporates several behavior change techniques (goal-setting, self-monitoring, and personalized feedback) as well as aiming to improve knowledge., Conclusions: A novel interactive mobile phone app was successfully developed based on requirements, and when tested in a pilot randomized controlled trial, this app was found to have some impacts on fruit and vegetable outcomes. Although benefits from the app were small, impacts will likely increase as a result of recent modifications. The final SMART 5-A-DAY app is available in the Google Play Store and now needs testing in the target population., Trial Registration: ClinicalTrials.gov NCT02779491; https://www.clinicaltrials.gov/ct2/show/NCT02779491., (©Katherine Marie Appleton, David Passmore, Isobel Burn, Hanna Pidgeon, Philippa Nation, Charlotte Boobyer, Nan Jiang. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 20.11.2019.)

McGuinness, A, Malone, S, Hughes, B, and Collins, K. Physical activity and physiological profiles of elite international female field hockey players across the quarters of competitive match play. J Strength Cond Res 33(9): 2513-2522, 2019-The aim of the current investigation was to quantify the physical and physiological demands of elite international female field hockey across the quarters of match-play. Twenty-seven elite international female field hockey outfield players (23 ± 3 years; 162.6 ± 13.0 cm; 66.0 ± 6.0 kg) participated in the current observational study during the 2016-2017 season. Participants were monitored using global positioning system technology and HR monitors. Players were categorized based on 3 different playing positions. Activity was categorized into total distance (in meters), relative total distance (m·min), low-, moderate-, and high-intensity distance (m), maximum velocity (km·h), and percentage maximal velocity (%). Physiological demands were quantified through players peak heart rate (HRPeak), which was classified based on the player's individual HRmax determined using a Yo-Yo intermittent recovery level 1 test. Players spent on average 38 ± 8 minutes in match play. The total distance covered was 4,847 ± 583 m (127.6 ± 15.6 m·min). Defenders covered a greater total distance across all 3 positions (p = ≤ 0.05). The midfielders covered a greater moderate-intensity distance (p ≤ 0.001), whereas the forwards covered more high-intensity distance (p ≤ 0.001). The HRpeak of the players was 198 ± 4 b·min with a mean exercise intensity of 95 ± 1% HRmax. The time spent >70% HRmax decreased significantly across the quarters (p = 0.01, η = 0.03). Defenders were found to spend more time >85% HRmax when compared with other positions (p ≤ 0.001, η = 0.28). The current study provides normative data that coaches should consider when developing training drills to better optimize the positional physical and physiological activity profiles that best replicate match play.

Although there is an extensive literature about talent development, the lack of data pertaining to females is problematic. Indeed, the gender data gap can be seen in practically all domains including sport and exercise medicine. Evidence-based practice is the systematic reviewing of the best evidence in order to make informed choices about practice. Unfortunately, it may be that the data collected in sport is typically about male experiences, and not female; a rather unfortunate omission given that approximately half of the population is made up of women. When female athletes are underrepresented in research there are issues when making inferences about data collected in male dominated research domains to inform practice and policy for female athletes. In parallel, female sport participation is continually increasing worldwide. Recognizing the importance of evidence-based practice in driving policy and practice, and reflecting the gender data gap that is a consistent feature of (almost) all other domains, we were interested in examining whether a gender data gap exists in talent development research. The results suggest that a gender data gap exists in talent development research across all topics. Youth athlete development pathways may be failing to recognize the development requirements of females, particularly where female sports may be borrowing systems that are perceived to work for their male counterparts. In order to ensure robust evidence based practice in female youth sport there is a need to increase the visibility of female athletes in talent development literature., (Copyright © 2019 Curran, MacNamara and Passmore.)

Uncialamycin analogs were evaluated as potential cytotoxic agents in an antibody-drug conjugate (ADC) approach to treating human cancer. These analogs were synthesized using Hauser annulations of substituted phthalides as a key step. A highly potent uncialamycin analog 3c with a valine-citrulline dipeptide linker was conjugated to an anti-mesothelin monoclonal antibody (mAb) through lysines to generate a meso-13 conjugate. This conjugate demonstrated subnanomolar potency (IC50 = 0.88 nM, H226 cell line) in in vitro cytotoxicity experiments with good immunological specificity to mesothelin-positive lung cancer cell lines. The potency and mechanism of action of this uncialamycin class of enediyne antitumor antibiotics make them attractive payloads in ADC-based cancer therapy., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

It has been suggested that intensive breeding has led to decreased contents of health-promoting components in modern wheats. We therefore compared the contents and compositions of the major dietary fibre components, arabinoxylan and β-glucan, in semolina and wholemeal flour of old and modern Italian durum wheats. No differences in total arabinoxylan content were observed but the modern varieties had higher proportions of soluble arabinoxylan in wholemeals and of β-glucan in semolina. The study therefore provides no evidence that intensive breeding has had negative effects on the contents of dietary fibre components in durum wheat. However, comparison of material grown over two years indicated that the content and composition of arabinoxylan and β-glucan were more stable in the older than in the modern genotypes. The identification of modern cultivars with high viscosity associated with a high content of β-glucan suggests that they are good sources of fibre for human health., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The data presented are related to the research article entitled "Comparison of the dietary fibre composition of old and modern durum wheat ( Triticum turgidum spp. durum ) genotypes" (De Santis et al., 2018) [1]. This article provides details of the structures of the major dietary fibre components, arabinoxylan and β-glucan, in semolina and wholemeal flour of old and modern Italian durum wheat genotypes grown in two seasons, determined by enzyme digestion followed by high-performance anion-exchange chromatography (enzyme fingerprinting).