What's in a Message? Effects of Mental Fatigue and Message Framing on Motivation for Physical Activity.

Many adults worldwide do not meet current physical activity (PA) guidelines. Mental fatigue decreases the likelihood of choosing to engage in PA. Message framing may enhance PA motivation when fatigued. We examined the effects of mental fatigue and message framing on PA motivation with additional focus on the messaging "congruency effect." Three hundred and twenty undergraduates completed measures of dispositional motivational orientation and were exposed to either gain-framed or loss-framed messages before completing an effort discounting questionnaire. Results showed lower motivation to engage in PA of higher intensities and longer durations. Direct effects of message framing on PA motivation were not significant. Interaction effects revealed that participants receiving messages congruent with their dominant motivational orientation showed increased motivation for light-intensity PA and decreased motivation for vigorous-intensity PA as mental fatigue increased. Findings suggest that providing messages congruent with one's dominant motivational orientation may increase motivation for engaging in light-intensity PA when fatigued.

Implementation of back to living well, a community-based program for the tertiary prevention of low back pain: a study protocol.

BACKGROUND: The current literature supports the effectiveness of exercise, education, and self-management interventions for the long-term management of persistent low back pain. However, there is significant uncertainty about the implementation of interventions related to barriers, facilitators, and patient's preferences. This study will evaluate the Back to Living Well program implementation from a participant and organizational perspective. More specifically we address the following objectives: 1) identify program barriers and facilitators from participants' perspectives, 2) identify factors related to program, personal and contextual factors that contribute to negative and positive outcomes, and outcome trajectories, 3) identify factors influencing participants' selection of an in-person or e-health program, and 4) evaluate program specific barriers and facilitators from the organization and care delivery perspectives. METHODS: This study will utilize a mixed-method convergent design including a longitudinal cohort strand and a longitudinal qualitative interview strand. The RE-AIM framework will be used to assess program implementation. Participants (n = 90, 1:1: in person or virtual) who choose to register in the program as well as staff (n = 10 to 15) involved in the delivery of the program will be invited to participate. Participants will participate in a 12-week physical activity, education, and self-management program. Implementation outcomes will be measured at 3-, 6-, 12-months, and six months after the end of the follow-ups. Interview scripts and directed content analysis will be constructed based on the Theoretical Domains Framework and the Neuromatrix Model of Pain, Theoretical Domains Framework. Staff interviews will be constructed and analyzed using the Consolidated Framework for Implementation Research. Participants will also complete pain, disability, quality of life and psychological questionnaires, wear an activity tracker at all time points, and complete weekly pain and activity limitation questions using a mobile application. DISCUSSION: The study results will provide evidence to inform potential future implementation of the program. An effective, appropriately targeted, and well implemented exercise program for the long-term management (i.e., tertiary prevention) of LBP could minimize the burden of the condition on patients, the health care system and society. TRIAL REGISTRATION: ClinicalTrials.gov NCT05929846. This (Registration Date: July 3 2023) study has been approved by the Hamilton Integrated Research Ethics Board Project ID#15,354.

Exploring the perspectives of older adults who are pre-frail and frail to identify interventions to reduce sedentary behaviour and improve mobility: a thematic content analysis.

Older adults who are frail are one of the most sedentary and the least physically active age groups. Prolonged sedentary time is associated with increased risk of negative health outcomes. To help design effective and sustainable content and optimize the uptake of sedentary behaviour interventions, an in-depth understanding of older adults' perceptions of sedentary behaviour is needed; however, most qualitative studies have been conducted in healthy older adults. The aim of this study was to explore perspectives of sedentary behaviour within the context of older adults who are pre-frail and frail after the winter and spring. We included participants if they: (1) spoke English or attended with a translator or caregiver, (2) were ≥ 60 years, and (3) were frail on the Morley Frail Scale. We utilized a qualitative description methodology including a semi-structured in-depth interview and thematic content analysis. Concepts from the COM-B (Capability Opportunity Motivation-Behaviour) model were used to guide the semi-structured interviews and analysis. To ensure credibility of the data, we used an audit trail and analyst triangulation. We recruited 21 older adults (72 ± 7.3 years, 13 females, 13 frail) from southwestern Ontario, Canada. Two individuals were lost to follow-up due to medical mistrust and worse health. We transcribed 39 audio recordings. We identified three salient themes: (1) older adults rationalize their sedentary behaviours through cognitive dissonance (reflective motivation), (2) urban cities in southwestern Ontario may not be "age-friendly" (physical opportunity), and (3) exercise is something people "have to do", but hobbies are for enjoyment despite medical conditions (psychological capability). Perspectives of sedentary behaviour were different in the winter versus spring, with participants perceiving themselves to be less active in winter. Incorporating dissonance-based interventions as part of an educational program could be used to target the reflective motivation and psychological capability components. Future research should consider interdisciplinary collaborations with environmental gerontology to develop age-friendly communities that promote meaningful mobility to target physical opportunity.

Mapping sedentary behaviour (MAPS-B) in winter and spring using wearable sensors, indoor positioning systems, and diaries in older adults who are pre-frail and frail: A feasibility longitudinal study.

Older adults who are frail are likely to be sedentary. Prior interventions to reduce sedentary time in older adults have not been effective as there is little research about the context of sedentary behaviour (posture, location, purpose, social environment). Moreover, there is limited evidence on feasible measures to assess context of sedentary behaviour in older adults. The aim of our study was to determine the feasibility of measuring context of sedentary behaviour in older adults with pre-frailty or frailty using a combination of objective and self-report measures. We defined "feasibility process" using recruitment (20 participants within two-months), retention (85%), and refusal (20%) rates and "feasibility resource" if the measures capture context and can be linked (e.g., sitting-kitchen-eating-alone) and are all participants willing to use the measures. Context was assessed using a wearable sensor to assess posture, a smart home monitoring system for location, and an electronic or hard-copy diary for purpose and social context over three days in winter and spring. We approached 80 potential individuals, and 58 expressed interest; of the 58 individuals, 37 did not enroll due to lack of interest or medical mistrust (64% refusal). We recruited 21 older adults (72±7.3 years, 13 females, 13 frail) within two months and experienced two dropouts due to medical mistrust or worsening health (90% retention). The wearable sensor, indoor positioning system, and electronic diary accurately captured one domain of context, but the hard copy was often not completed with enough detail, so it was challenging to link it to the other devices. Although not all participants were willing to use the wearable sensor, indoor positioning system, or electronic diary, we were able to triage the measures of those who did. The use of wearable sensors and electronic diaries may be a feasible method to assess context of sedentary behaviour, but more research is needed with device-based measures in diverse groups.

The contribution and interplay of implicit and explicit processes on physical activity behavior: empirical testing of the physical activity adoption and maintenance (PAAM) model.

The adoption and maintenance of physical activity (PA) is an important health behavior. This paper presents the first comprehensive empirical test of the Physical Activity Adoption and Maintenance (PAAM) model, which proposes that a combination of explicit (e.g., intention) and implicit (e.g., habit,, affect) self-regulatory processes is involved in PA adoption and maintenance. Data were collected via online questionnaires in English, German, and Italian at two measurement points four weeks apart. The study included 422 participants (Mage= 25.3, SDage= 10.1; 74.2% women) from Germany, Switzerland, Italy, Canada, and the U.S. The study results largely supported the assumptions of the PAAM model, indicating that intentions and habits significantly mediate the effects of past PA on future PA. In addition, the effect of past PA on future PA was shown to be significant through a mediation chain involving affect and habit. Although the hypothesis that trait self-regulation moderates the intention-behavior relationship was not supported, a significant moderating effect of affect on the same relationship was observed. The results suggest that interventions targeting both explicit and implicit processes may be effective in promoting PA adoption and maintenance.

Investigating real-time physical activity behavior using ecological momentary assessment: Effects of mental fatigue and benefit-cost valuations.

BACKGROUND: Current research investigating the relationship between mental fatigue and physical activity behaviors relies on laboratory-based, experimental studies which lack ecological validity. OBJECTIVE: This study used ecological momentary assessment (EMA) to assess feelings of mental fatigue and subjective evaluations (benefits and costs) as predictors of moderate-to-vigorous intensity physical activity in the everyday lives of young adults. METHODS: One hundred participants (n = 22 males, n = 78 females, Mage = 20.60 years, 70% meeting or exceeding physical activity guidelines) responded to digital survey prompts up to four times a day and wore an accelerometer for seven consecutive days. Moderate-to-vigorous intensity physical activity in the 180-min time window following each survey prompt was recorded. Data from the 28 survey-moderate-to-vigorous intensity physical activity epochs were analyzed using multilevel mixed-effects linear modelling. RESULTS: Higher levels of mental fatigue than one's average level were associated with engaging in fewer moderate-to-vigorous intensity physical activity minutes (p = .004) and lower benefit vs. cost scores (p = .001). Higher benefit vs. cost scores than one's average level were associated with engaging in more minutes of moderate-to-vigorous intensity physical activity (p < .001). CONCLUSIONS: Results are the first to demonstrate outside the lab, that mental fatigue experienced in everyday life may amplify the perceived costs of moderate-to-vigorous intensity physical activity, with both factors playing a potential role in moderate-to-vigorous intensity physical activity decision-making. Future research may apply insights gained from this study in design and testing of real-time interventions promoting moderate-to-vigorous intensity physical activity.

Computational pharmacogenotype extraction from clinical next-generation sequencing.

Background: Next-generation sequencing (NGS), including whole genome sequencing (WGS) and whole exome sequencing (WES), is increasingly being used for clinic care. While NGS data have the potential to be repurposed to support clinical pharmacogenomics (PGx), current computational approaches have not been widely validated using clinical data. In this study, we assessed the accuracy of the Aldy computational method to extract PGx genotypes from WGS and WES data for 14 and 13 major pharmacogenes, respectively. Methods: Germline DNA was isolated from whole blood samples collected for 264 patients seen at our institutional molecular solid tumor board. DNA was used for panel-based genotyping within our institutional Clinical Laboratory Improvement Amendments- (CLIA-) certified PGx laboratory. DNA was also sent to other CLIA-certified commercial laboratories for clinical WGS or WES. Aldy v3.3 and v4.4 were used to extract PGx genotypes from these NGS data, and results were compared to the panel-based genotyping reference standard that contained 45 star allele-defining variants within CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, CYP4F2, DPYD, G6PD, NUDT15, SLCO1B1, TPMT, and VKORC1. Results: Mean WGS read depth was >30x for all variant regions except for G6PD (average read depth was 29 reads), and mean WES read depth was >30x for all variant regions. For 94 patients with WGS, Aldy v3.3 diplotype calls were concordant with those from the genotyping reference standard in 99.5% of cases when excluding diplotypes with additional major star alleles not tested by targeted genotyping, ambiguous phasing, and CYP2D6 hybrid alleles. Aldy v3.3 identified 15 additional clinically actionable star alleles not covered by genotyping within CYP2B6, CYP2C19, DPYD, SLCO1B1, and NUDT15. Within the WGS cohort, Aldy v4.4 diplotype calls were concordant with those from genotyping in 99.7% of cases. When excluding patients with CYP2D6 copy number variation, all Aldy v4.4 diplotype calls except for one CYP3A4 diplotype call were concordant with genotyping for 161 patients in the WES cohort. Conclusion: Aldy v3.3 and v4.4 called diplotypes for major pharmacogenes from clinical WES and WGS data with >99% accuracy. These findings support the use of Aldy to repurpose clinical NGS data to inform clinical PGx.

The Geras virtual frailty rehabilitation program to build resilience in older adults with frailty during COVID-19: a randomized feasibility trial.

BACKGROUND: The Coronavirus (COVID-19) pandemic has exacerbated the risk for poor physical and mental health outcomes among vulnerable older adults. Multicomponent interventions could potentially prevent or reduce the risk of becoming frail; however, there is limited evidence about utilizing alternative modes of delivery where access to in-person care may be challenging. This randomized feasibility trial aimed to understand how a multicomponent rehabilitation program can be delivered remotely to vulnerable older adults with frailty during the pandemic. METHODS: Participants were randomized to either a multimodal or socialization arm. Over a 12-week intervention period, the multimodal group received virtual care at home, which included twice-weekly exercise in small group physiotherapy-led live-streamed sessions, nutrition counselling and protein supplementation, medication consultation via a videoconference app, and once-weekly phone calls from student volunteers, while the socialization group received only once-weekly phone calls from the volunteers. The RE-AIM (Reach, Effectiveness, Adoption, Implementation and Maintenance) framework was used to evaluate the feasibility of the program. The main clinical outcomes were change in the 5-times sit-to-stand test (5 × STS) and Depression, Anxiety and Stress Scale (DASS-21) scores. The feasibility outcomes were analyzed using descriptive statistics and expressed as frequencies and mean percent with corresponding confidence intervals (CI). Analysis of covariance (ANCOVA) was used for the effectiveness component. RESULTS: The program enrolled 33% (n = 72) of referrals to the study (n = 220), of whom 70 were randomized. Adoption rates from different referral sources were community self-referrals (60%), community organizations (33%), and healthcare providers (25%). At the provider level, implementation rates varied from 75 to 100% for different aspects of program delivery. Participant's adherence levels included virtual exercise sessions 81% (95% CI: 75-88%), home-based exercise 50% (95% CI: 38-62%), protein supplements consumption 68% (95% CI: 55-80%), and medication optimization 38% (95% CI: 21-59%). Most participants (85%) were satisfied with the program. There were no significant changes in clinical outcomes between the two arms. CONCLUSION: The GERAS virtual frailty rehabilitation study for community-dwelling older adults living with frailty was feasible in terms of reach of participants, adoption across referral settings, adherence to implementation, and participant's intention to maintain the program. This program could be feasibly delivered to improve access to socially isolated older adults where barriers to in-person participation exist. However, trials with larger samples and longer follow-up are required to demonstrate effectiveness and sustained behavior change. TRIAL REGISTRATION: ClinicalTrials.gov NCT04500366. Registered August 5, 2020, https://clinicaltrials.gov/ct2/show/NCT04500366.

Physical Activity Trajectories in Early Childhood: Investigating Personal, Environmental, and Participation Factors.

INTRODUCTION/PURPOSE: To determine personal, environmental, and participation factors that predict children's physical activity (PA) trajectories from preschool through to school years. METHODS: Two hundred seventy-nine children (4.5 ± 0.9 yr, 52% boys) were included in this study. Physical activity was collected via accelerometry at six different timepoints over 6.3 ± 0.6 yr. Time-stable variables were collected at baseline and included child's sex and ethnicity. Time-dependent variables were collected at six timepoints (age, years) and included household income (CAD), parental total PA, parental influence on PA, and parent-reported child's quality of life, child's sleep, and child's amount of weekend outdoor PA. Group-based trajectory modeling was applied to identify trajectories of moderate-to-vigorous PA (MVPA) and total PA (TPA). Multivariable regression analysis identified personal, environmental, and participation factors associated with trajectory membership. RESULTS: Three trajectories were identified for each of MVPA and TPA. Group 3 in MVPA and TPA expressed the most PA over time, with increased activity from timepoints 1 to 3, and then declining from timepoints 4 to 6. For the group 3 MVPA trajectory, male sex (ß estimate, 3.437; P = 0.001) and quality of life (ß estimate, 0.513; P < 0.001) were the only significant correlates for group membership. For the group 3 TPA trajectory, male sex (ß estimate, 1.970; P = 0.035), greater household income (ß estimate, 94.615; P < 0.001), and greater parental total PA (ß estimate, 0.574; P = 0.023) increased the probability of belonging to this trajectory group. CONCLUSIONS: These findings suggest a need for interventions and public health campaigns to increase opportunities for PA engagement in girls starting in the early years. Policies and programs to address financial inequities, positive parental modeling, and improving quality of life are also warranted.

Is It Really Worth the Effort? Examining the Effects of Mental Fatigue on Physical Activity Effort Discounting.

Physical activity (PA) guidelines are informed by epidemiological evidence but do not account for people's motivation for exerting physical effort. Previous research has shown that people are less motivated to engage in moderate- to vigorous-intensity PA when fatigued. In a two-study series, we investigated how intensity and duration affected people's willingness to engage in PA using an effort-discounting paradigm. A secondary purpose was to examine whether effort discounting was affected by mental fatigue. Both studies revealed a significant Intensity × Duration interaction demonstrating a reduced willingness to engage in PA of higher intensities across increasing duration levels. Study 1 demonstrated greater effort discounting for vigorous-intensity PA with increasing mental fatigue; however, this effect was not observed in Study 2. Findings provide novel insight toward people's motivation for engaging in PA based on the properties of the task, and some evidence suggesting feelings of fatigue may also influence motivation to exert physical effort.

Understanding Changes in Adolescent Physical Activity Behaviors and Cognitions Prior to and During the COVID-19 Pandemic.

Despite accumulating evidence that has found significant negative declines in physical activity (PA) as a result of the COVID-19 pandemic, little work has sought to understand how PA cognitions have changed during this period and in relation to behavior change during the pandemic. The purpose of the current study was to investigate the changes in adolescents' PA behaviors and cognitions associated with COVID-19 and prospective predictors of PA using the Multi-Process Action Control (M-PAC) framework. Adolescents were recruited from a large school board and a total of 588 participants (Mage = 15.87 ± 0.43 years, 60% female) completed data collection in both Fall 2019 and 2020-prior to and during the COVID-19 pandemic. Participants completed self-reported measures of moderate-to-vigorous PA (MVPA), participation in organized activities, and variables derived from the M-PAC framework. Mixed effects models were computed to examine longitudinal changes in MVPA and cognitions as well as whether cognitions prior to COVID-19 predict MVPA during COVID-19. A generalized estimating equations model was computed to examine longitudinal changes for participation in organized activities. Findings indicated that MVPA (B = -56.41, p < 0.01) and participation in organized activities (OR = 0.33, p < 0.01) significantly decreased during the COVID-19 pandemic. Correspondingly, there were significant decreases in intentions (B = -0.34), identity (B = -0.19), and habit (B = -0.20), though there were increases in behavioral regulation (B = 0.18). No significant changes were found in affective attitudes, instrumental attitudes, perceived opportunity, and perceived capability. Among the baseline M-PAC cognitions, habit (B = 46.28) was the lone significant predictor of MVPA during COVID-19. Overall results suggest that adolescents' PA behaviors and cognitions were negatively impacted by the COVID-19 pandemic, along with promising evidence that restrictions prompted adaptive utilization of behavioral regulation skills. Moreover, habit appears to play a salient role in predicting PA behaviors during uncertain times involving major life disruptions. These findings highlight the need to dedicate additional attention to PA promotion as COVID-19 moves toward an endemic phase, and that interventions targeting habit formation may be critical for helping adolescents better sustain healthy active lifestyles during major life changes.

Initial Phase I Safety Study of Gedatolisib plus Cofetuzumab Pelidotin for Patients with Metastatic Triple-Negative Breast Cancer.

PURPOSE: The PI3K pathway is dysregulated in the majority of triple-negative breast cancers (TNBC), yet single-agent inhibition of PI3K has been ineffective in TNBC. PI3K inhibition leads to an immediate compensatory upregulation of the Wnt pathway. Dual targeting of both pathways is highly synergistic against TNBC models in vitro and in vivo. We initiated a phase I clinical trial combining gedatolisib, a pan-class I isoform PI3K/mTOR inhibitor, and cofetuzumab pelidotin, an antibody-drug conjugate against the cell-surface PTK7 protein (Wnt pathway coreceptor) with an auristatin payload. PATIENTS AND METHODS: Participants (pt) had metastatic TNBC or estrogen receptor (ER) low (ER and PgR < 5%, HER2-negative) breast cancer, and had received at least one prior chemotherapy for advanced disease. The primary objective was safety. Secondary endpoints included overall response rate (ORR), clinical benefit at 18 weeks (CB18), progression-free survival (PFS), and correlative analyses. RESULTS: A total of 18 pts were enrolled in three dose cohorts: gedatolisib 110 mg weekly + cofetuzumab pelidotin 1.4 mg/kg every 3 weeks (n = 4), 180 mg + 1.4 mg/kg (n = 3), and 180 mg + 2.8 mg/kg (n = 11). Nausea, anorexia, fatigue, and mucositis were common but rarely reached ≥grade 3 severity. Myelosuppression was uncommon. ORR was 16.7% (3/18). An additional 3 pts had stable disease (of these 2 had stable disease for >18 weeks); CB18 was 27.8%. Median PFS was 2.0 months (95% confidence interval for PFS: 1.2-6.2). Pts with clinical benefit were enriched with genomic alterations in the PI3K and PTK7 pathways. CONCLUSIONS: The combination of gedatolisib + cofetuzumab pelidotin was well tolerated and demonstrated promising clinical activity. Further investigation of this drug combination in metastatic TNBC is warranted.

Analytical Validation of a Computational Method for Pharmacogenetic Genotyping from Clinical Whole Exome Sequencing.

Germline whole exome sequencing from molecular tumor boards has the potential to be repurposed to support clinical pharmacogenomics. However, accurately calling pharmacogenomics-relevant genotypes from exome sequencing data remains challenging. Accordingly, this study assessed the analytical validity of the computational tool, Aldy, in calling pharmacogenomics-relevant genotypes from exome sequencing data for 13 major pharmacogenes. Germline DNA from whole blood was obtained for 164 subjects seen at an institutional molecular solid tumor board. All subjects had whole exome sequencing from Ashion Analytics and panel-based genotyping from an institutional pharmacogenomics laboratory. Aldy version 3.3 was operationalized on the LifeOmic Precision Health Cloud with copy number fixed to two copies per gene. Aldy results were compared with those from genotyping for 56 star allele-defining variants within CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, CYP4F2, DPYD, G6PD, NUDT15, SLCO1B1, and TPMT. Read depth was >100× for all variants except CYP3A4∗22. For 75 subjects in the validation cohort, all 3393 Aldy variant calls were concordant with genotyping. Aldy calls for 736 diplotypes containing alleles assessed by both platforms were also concordant. Aldy identified additional star alleles not covered by targeted genotyping for 139 diplotypes. Aldy accurately called variants and diplotypes for 13 major pharmacogenes, except for CYP2D6 variants involving copy number variations, thus allowing repurposing of whole exome sequencing to support clinical pharmacogenomics.

Preschool to School-Age Physical Activity Trajectories and School-Age Physical Literacy: A Longitudinal Analysis.

PURPOSE: The associations between longitudinal physical activity (PA) patterns across childhood and physical literacy have not been studied. The purpose of this study was to identify PA trajectories from preschool to school-age, and to determine if trajectory group membership was associated with school-age physical literacy. METHODS: Participants (n = 279, 4.5 [0.9] y old, 48% girls) enrolled in this study and completed annual assessments of PA with accelerometry over 6 timepoints. Physical literacy was assessed at timepoint 6 (10.8 [1.0] y old). Group-based trajectory analysis was applied to identify trajectories of total volume of PA and of moderate to vigorous PA and to estimate group differences in physical literacy. RESULTS: Three trajectories of total volume of PA and of moderate to vigorous PA were identified. Groups 1 (lowest PA) included 40% to 53% of the sample, groups 2 included 39% to 44% of the sample, and groups 3 (highest PA) included 8% to 16% of the sample. All trajectories declined from timepoint 1 to timepoint 6. School-age physical literacy was lowest in trajectory groups with the lowest total volume of PA or moderate to vigorous PA over time (P < .05). CONCLUSIONS: PA should be promoted across early and middle childhood, as it may play a formative role in the development of school-age physical literacy.

Modelling the disappearance of coarse woody debris, following a land clearing event.

BACKGROUND: Land clearing generates coarse woody debris (CWD), much of which ultimately becomes atmospheric CO2. Schemes for greenhouse gas accounting must consider the contribution from land clearing, but the timing of the contribution will have large uncertainty, due to a paucity of knowledge about the rate of CWD disappearance. To better understand above-ground CWD disappearance following a land clearing event-through the actions of microorganisms, invertebrates, wildfire, or deliberate burning-we combined statistical modelling with an archive of semi-quantitative observations (units of CWD %), made within Queensland, Australia. RESULTS: Using a generalised additive mixed-effects model (median absolute error = 14.7%), we found that CWD disappearance was strongly influenced by the: (i) number of years elapsed since clearing; (ii) clearing method; (iii) bioregion (effectively a climate-by-tree species interaction); and (iv) the number of times burned. Years-since-clearing had a strongly non-linear effect on the rate of CWD disappearance. The data suggested that disappearance was reverse-sigmoidal, with little change in CWD apparent for the first three years after clearing. In typical conditions for Queensland, the model predicted that it will take 38 years for 95% of CWD to disappear, following a land clearing event; however, accounting for uncertainty in the data and model, this value could be as few as 5 years, or > 100 years. In contrast, due to an assumption about the propensity of land managers to burn CWD, the official method used to assess Australia's greenhouse gas emissions predicted that 95% of CWD will disappear in < 1 year. CONCLUSIONS: In Queensland, the CWD generated by land clearing typically takes 38 years to disappear. This ultimately implies that a key assumption of Australia's official greenhouse gas reporting-i.e. that 98% of CWD is burned soon after a clearing event-does not adequately account for delayed CO2 emissions.

Investigating the Effects of Mental Fatigue on Resistance Exercise Performance.

Mental fatigue can impart negative effects on subsequent physical performance, although the mechanisms underlying these effects are not well understood. This study examined whether mental fatigue confers negative carryover effects on the performance of a set of biceps curls, while also investigating physiological and psychological mechanisms proposed to explain the predicted effect. A randomized, cross-over design was employed. On visit 1, participants (N = 10) performed a barbell biceps curl one-repetition maximum (1RM) test. On visits 2-3, participants performed 20 biceps curls at 50% of their 1RM, followed by their respective 10 min experimental manipulation (high vs. low cognitive exertion) and then a second set of biceps curls to exhaustion. Ratings of perceived exertion and electromyography of the biceps brachii, triceps brachii, upper trapezius, thoracic erector spinae and lumbar erector spinae were recorded during the physical task. The total number of repetitions completed was similar across the conditions. Results also failed to show between-condition differences for muscle activation and perceptions of exertion. Future research is needed to build an adequate knowledge base to determine whether there is an effect of mental fatigue on dynamic resistance-based task performance and, if so, identify the mechanisms explaining how and why.

Potential Utility of Pre-Emptive Germline Pharmacogenetics in Breast Cancer.

Patients with breast cancer often receive many drugs to manage the cancer, side effects associated with cancer treatment, and co-morbidities (i.e., polypharmacy). Drug-drug and drug-gene interactions contribute to the risk of adverse events (AEs), which could lead to non-adherence and reduced efficacy. Here we investigated several well-characterized inherited (germline) pharmacogenetic (PGx) targets in 225 patients with breast cancer. All relevant clinical, pharmaceutical, and PGx diplotype data were aggregated into a single unifying informatics platform to enable an exploratory analysis of the cohort and to evaluate pharmacy ordering patterns. Of the drugs recorded, there were 38 for which high levels of evidence for clinical actionability with PGx was available from the US FDA and/or the Clinical Pharmacogenetics Implementation Consortium (CPIC). These data were associated with 10 pharmacogenes: DPYD, CYP2C9, CYP2C19, CYP2D6, CYP3A5, CYP4F2, G6PD, MT-RNR1, SLCO1B1, and VKORC1. All patients were taking at least one of the 38 drugs and had inherited at least one actionable PGx variant that would have informed prescribing decisions if this information had been available pre-emptively. The non-cancer drugs with PGx implications that were common (prescribed to at least one-third of patients) included anti-depressants, anti-infectives, non-steroidal anti-inflammatory drugs, opioids, and proton pump inhibitors. Based on these results, we conclude that pre-emptive PGx testing may benefit patients with breast cancer by informing drug and dose selection to maximize efficacy and minimize AEs.

Effects of dance on cognitive function in older adults: a systematic review and meta-analysis.

BACKGROUND: dance is a mind-body activity that stimulates neuroplasticity. We explored the effect of dance on cognitive function in older adults. METHODS: we searched MEDLINE, EMBASE, CENTRAL and PsycInfo databases from inception to August 2020 (PROSPERO:CRD42017057138). Inclusion criteria were (i) randomised controlled trials (ii) older adults (aged ≥ 55 years), (iii) intervention-dance and (iv) outcome-cognitive function. Cognitive domains were classified with the Diagnostic and Statistical Manual of Mental Disorders-5 Neurocognitive Framework. Meta-analyses were performed in RevMan5.3 and certainty of evidence with GradePro. RESULTS: we reviewed 3,997 records and included 11 studies (N = 1,412 participants). Seven studies included only healthy older adults and four included those with mild cognitive impairment (MCI). Dance interventions varied in frequency (1-3×/week), time (35-60 minutes), duration (3-12 months) and type. We found a mean difference (MD) = 1.58 (95% confidence interval [CI) = 0.21-2.95) on the Mini Mental State Examination for global cognitive function (moderate-certainty evidence), and the Wechsler Memory Test for learning and memory had an MD = 3.02 (95% CI = 1.38-4.65; low-certainty evidence). On the Trail Making Test-A for complex attention, MD = 3.07 (95% CI = -0.81 to 6.95; high-certainty evidence) and on the Trail Making Test-B for executive function, MD = -4.12 (95% CI = -21.28 to 13.03; moderate-certainty evidence). Subgroup analyses did not suggest consistently greater effects in older adults with MCI. Evidence is uncertain for language, and no studies evaluated social cognition or perceptual-motor function. CONCLUSIONS: dance probably improves global cognitive function and executive function. However, there is little difference in complex attention, and evidence also suggests little effect on learning and memory. Future research is needed to determine the optimal dose and if dance results in greater cognitive benefits than other types of physical activity and exercise.

Measurement properties of the Physical Literacy Assessment for Youth (PLAY) Tools.

The Physical Literacy Assessment for Youth (PLAY) Tools are a suite of tools to assess an individual's physical literacy. The purpose of this study is to examine the psychometric properties of the PLAY Tools, including inter-rater reliability, internal consistency, validity and the associations between the tools. In this study, 218 children and youth (aged 8.4 to 13.7 years) and a parent/guardian completed the appropriate physical literacy assessments (i.e., PLAYbasic, PLAYfun, PLAYparent and PLAYself) and the Bruiniks-Oseretsky Test of Motor Proficiency (BOT-2). Inter-rater reliability for PLAYfun was excellent (intraclass correlation coefficient = 0.94). The PLAYbasic, PLAYfun total, running and object control scores, and PLAYparent motor competence domain were higher in males than females, and PLAYfun locomotor skills were lower in males than females (p < 0.05). Age was positively correlated with PLAYbasic and PLAYfun (r = 0.14-0.32, p < 0.05). BOT-2 was positively correlated with PLAYfun and PLAYbasic (r = 0.19-0.59, p < 0.05). PLAYbasic is a significant predictor of PLAYfun (r2 = 0.742, p < 0.001). PLAYfun, PLAYparent and PLAYself were moderately correlated with one another. PLAYfun, PLAYparent and PLAYself demonstrated acceptable internal consistency (α = 0.74-0.87, ω = 0.73-0.87). The PLAY Tools demonstrated moderate associations between one another, strong inter-rater reliability and good construct and convergent validity. Continued evaluation of these tools with other populations, such as adolescents, is necessary. Novelty: In school-age children, the PLAY Tools demonstrated strong inter-rater reliability, moderate associations with one another, acceptable internal consistency and good construct and convergent validity. The results suggest that that PLAY Tools are an acceptable method of evaluation for physical literacy in school-age children.

Evaluation of molecular subtypes and clonal selection during establishment of patient-derived tumor xenografts from gastric adenocarcinoma.

Patient-derived xenografts (PDX) have emerged as an important translational research tool for understanding tumor biology and enabling drug efficacy testing. They are established by transfer of patient tumor into immune compromised mice with the intent of using them as Avatars; operating under the assumption that they closely resemble patient tumors. In this study, we established 27 PDX from 100 resected gastric cancers and studied their fidelity in histological and molecular subtypes. We show that the established PDX preserved histology and molecular subtypes of parental tumors. However, in depth investigation of the entire cohort revealed that not all histological and molecular subtypes are established. Also, for the established PDX models, genetic changes are selected at early passages and rare subclones can emerge in PDX. This study highlights the importance of considering the molecular and evolutionary characteristics of PDX for a proper use of such models, particularly for Avatar trials.