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BACKGROUND AND AIMS The use of forceps for removal of non-diminutive polyps is associated with incomplete resection compared to snare polypectomy. However, few studies have characterized the frequency of forceps polypectomy for non-diminutive polyps or identified strategies to improve this practice. To address this gap, we estimated prevalence and predictors of forceps polypectomy in clinical practice and examined the effectiveness of a multi-component intervention to reduce inappropriate forceps polypectomy. METHODS We retrospectively reviewed all colonoscopies with polypectomies performed at two U.S. health systems between 10/1/2017 and 9/30/2019. We used a mixed-effects logistic regression model to examine the effect of a multi-component intervention, including provider education and a financial incentive, to reduce inappropriate forceps polypectomy, defined as use of forceps polypectomy for polyps ≥5mm. RESULTS A total of 9968 colonoscopies with 25534 polypectomies were performed by 42 gastroenterologists during the study period. Overall, 8.5% (n=2176) of polyps were removed with inappropriate forceps polypectomy. Inappropriate forceps polypectomy significantly decreased after the intervention (OR 0.34, 95% CI 0.30-0.39), from 11.4% (n=1539) to 5.3% (n=637). Predictors of inappropriate forceps polypectomy included: inadequate bowel prep (OR 1.25, 95% CI 1.06 – 1.47), polyps in the right colon (vs. left: OR 1.29, 95% CI 1.09 – 1.51), and number of polyps removed (OR 0.96, 95% CI 0.94 – 0.97). Inappropriate forceps polypectomy also varied by gastroenterologist (median odds ratio 3.43). In a post-hoc analysis, the proportion of polyps >2mm removed with forceps decreased from 50.0% before the intervention to 43.0% after it (OR 0.62, 95% CI 0.58-0.68). CONCLUSIONS Inappropriate forceps polypectomy is common but modifiable. The proportion of non-diminutive polyps removed with forceps polypectomy should be considered as a quality measure.

In the absence of stress, crop growth depends on the amount of light intercepted by the canopy and the conversion efficiency [radiation use efficiency (RUE)]. This study tested the hypothesis that long-term genetic gain for grain yield was partly due to improved RUE. The hypothesis was tested using 30 elite maize hybrids commercialized in the US corn belt between 1930 and 2017. Crops grown under irrigation showed that pre-flowering crop growth increased at a rate of 0.11 g m–2 year–1, while light interception remained constant. Therefore, RUE increased at a rate of 0.0049 g MJ–1 year–1, translating into an average of 3 g m–2 year–1 of grain yield over 100 years of maize breeding. Considering that the harvest index has not changed for crops grown at optimal density for the hybrid, the cumulative RUE increase over the history of commercial maize breeding in the USA can account for ~32% of the documented yield trend for maize grown in the central US corn belt. The remaining RUE gap between this study and theoretical maximum values suggests that a yield improvement of a similar magnitude could be achieved by further increasing RUE.

During pregnancy, assessment of cardiac output (𝑄̇), a fundamental measure of cardiovascular function, provides important insight into maternal adaptation. However, methods for dynamic 𝑄̇ measurement require validation. The purpose of this study was to estimate the agreement of 𝑄̇ measured by echocardiography and Modelflow® at rest and during submaximal exercise in non-pregnant (n = 18), pregnant (n = 15, 22-26 weeks gestation) and postpartum women (n = 12, 12-16 weeks post-delivery). Simultaneous measurements of 𝑄̇ derived from echocardiography [criterion] and Modelflow® were obtained at rest and during low-moderate intensity (25% and 50% peak power output) cycling exercise and compared using Bland-Altman analysis and limits of agreement. Agreement between echocardiography and Modelflow® was poor in non-pregnant, pregnant and postpartum women at rest (mean difference ± SD: -1.1 ± 3.4; -1.2 ± 2.9; -1.9 ± 3.2 L.min-1), and this remained evident during exercise. The Modelflow® method is not recommended for 𝑄̇ determination in research involving young, healthy non-pregnant and pregnant women at rest or during dynamic challenge. Previously published 𝑄̇ data from studies utilising this method should be interpreted with caution.

Byrne, PJ, Moody, JA, Cooper, SM, and Kinsella, S. Acute effects of "composite" training on neuromuscular and fast stretch-shortening cycle drop jump performance in hurling players. J Strength Cond Res 35(12): 3474-3481, 2021-"Composite" training is a term developed by the authors and defined as the combination of a plyometric exercise with an explosive activity such as a sprint run, performed as a "combined repetition"/session. The purposes of this study were to investigate the acute effect of a "composite" training session on neuromuscular and fast stretch-shortening cycle bounce drop jumps (BDJs) in hurling players' immediately, after session, and after 7 days of recovery. Eight hurling players first completed a drop jump test to identify individual BDJ drop height, followed 72 hours later with a single "composite" training session. Three repetition maximum (3RM) back squat strength, BDJ, countermovement jump (CMJ), and sprint performance testing were performed 10 minutes before and immediately after session and 7 days after session. An analysis of variance reported a significant decrease in CMJ measures (height, velocity, and eccentric rate of force development) and sprint performance from presession to postsession (p ≤ 0.05). Moreover, a significant increase was evident for CMJ performance (height and power), sprint performance (5 and 20 m), 3RM back squat strength, and BDJ performance (reactive strength index and height) from postsession to post-7-day recovery (p ≤ 0.05). Pairwise comparisons indicated that absolute and relative 3RM strength significantly increased from presession to post-7 days (absolute 3RM: p = 0.0001; relative 3RM: p = 0.01). The findings indicate that "composite" training results in an immediate decline in CMJ measures after session possibly due to acute muscle fatigue, and supercompensation augments maximum lower-limb strength after 7 days of recovery.

A major focus for genomic prediction has been on improving trait prediction accuracy using combinations of algorithms and the training data sets available from plant breeding multi-environment trials (METs). Any improvements in prediction accuracy are viewed as pathways to improve traits in the reference population of genotypes and product performance in the target population of environments (TPE). To realize these breeding outcomes there must be a positive MET-TPE relationship that provides consistency between the trait variation expressed within the MET data sets that are used to train the genome-to-phenome (G2P) model for applications of genomic prediction and the realized trait and performance differences in the TPE for the genotypes that are the prediction targets. The strength of this MET-TPE relationship is usually assumed to be high, however it is rarely quantified. To date investigations of genomic prediction methods have focused on improving prediction accuracy within MET training data sets, with less attention to quantifying the structure of the TPE and the MET-TPE relationship and their potential impact on training the G2P model for applications of genomic prediction to accelerate breeding outcomes for the on-farm TPE. We extend the breeder’s equation and use an example to demonstrate the importance of the MET-TPE relationship as a key component for the design of genomic prediction methods to realize improved rates of genetic gain for the target yield, quality, stress tolerance and yield stability traits in the on-farm TPE.

Breeding climate-resilient crops with improved levels of abiotic and biotic stress resistance as a response to climate change presents both opportunities and challenges. Applying the framework of the “breeder’s equation,” which is used to predict the response to selection for a breeding program cycle, we review methodologies and strategies that have been used to successfully breed crops with improved levels of drought resistance, where the target population of environments (TPEs) is a spatially and temporally heterogeneous mixture of drought-affected and favorable (water-sufficient) environments. Long-term improvement of temperate maize for the US corn belt is used as a case study and compared with progress for other crops and geographies. Integration of trait information across scales, from genomes to ecosystems, is needed to accurately predict yield outcomes for genotypes within the current and future TPEs. This will require transdisciplinary teams to explore, identify, and exploit novel opportunities to accelerate breeding program outcomes; both improved germplasm resources and improved products (cultivars, hybrids, clones, and populations) that outperform and replace the products in use by farmers, in combination with modified agronomic management strategies suited to their local environments.

Transgenes have been successfully commercialized for qualitatively inherited insect and herbicide resistance traits that show similar effects across genetic backgrounds. However, for quantitative traits like yield, genetic background may affect the measured transgene value. In this paper, we evaluated whether different genetic backgrounds impact the estimated value of a transgene for grain yield, ear height, and anthesis-silking interval for maize by developing isogenic pairs of lines with and without a transgene and testing them in hybrid combination with non-transgenic lines from a complementary heterotic group across eleven environments in the USA. Over all hybrid combinations, the transgene increased yield by 0.2 Mg ha−1. Across multiple non-transgenic lines of the opposing heterotic group, the transgene effect within a line pair ranged from an increase of 0.8 Mg ha−1for the NSS4 and SS7 transgenic lines to a reduction of 0.3 Mg ha−1for the NSS5 transgenic line when compared to their non-transgenic isoline. Transgenic hybrids were often taller than non-transgenic hybrids (P

The Tropical Conservativism Hypothesis and Biogeographical Conservativism Hypothesis were tested in forest millipedes. Latitudinal diversity gradient (LDG) was measured in the genus Sphaerotherium and Tetraconasoma to distinguish between the two hypotheses. There was a marginally significant correlation between the number of species and latitudinal degrees away from the equator in Tetraconasoma (r=-0.78091517, Z score=-1.48168825, n=5, p=0.06921166), not Sphaerotherium (r=-0.73029674, Z score=-0.92936295, n=4, p=0.17635049). The relationship in Tetraconasoma was shown to be significant (Spearman's Rho rs=-0.89443, p (2-tailed) = 0.04052). An evolutionary preference for temperate environments appearing to have led to climatic constraints on dispersal based primarily on precipitation seasonality gradients was previously suggested. The antennal cone cells in the Tetraconasoma are suggested to be responsible for this sensory adaptive radiation and variation.

To identify types of nurse-led interventions for multimorbidity and which outcomes are positively affected by them.Mixed-methods systematic review following the Joanna Briggs Institute (JBI) methods for convergent-integrated reviews.CRD42020197956.Cochrane CENTRAL, CINAHL, Embase and MEDLINE were searched in October 2020. Grey literature sources included OpenGrey, the Journal of Multimorbidity and Comorbidity and reference mining.English-language reports of nurse-led interventions for people with multimorbidity were included based on author consensus. Two reviewers performed independent quality appraisal using JBI tools. Data were extracted and synthesized using a pre-existing taxonomy of interventions and core outcome set.Twenty studies were included, with a median summary quality score of 77.5%. Interventions were mostly case-management or transitional care interventions, with nurses in advanced practice, support to self-manage conditions, and an emphasis on continuity of care featuring frequently. Patient-centred outcomes such as quality of healthcare and health-related quality of life were mostly improved, with mixed effects on healthcare utilization, costs, mortality and other outcomes.Interventions such as case management are agreeable to patients and transitional care interventions may have a small positive impact on healthcare utilization. Interventions include long-term patient management or short-term interventions targeted at high-risk junctures. These interventions feature nurses in advanced practice developing care plans in partnership with patients, to simplify and improve the quality of care both in the long and short-term.This is the first mixed-methods review which includes all types of nurse-led interventions for multimorbidity and does not focus on specific comorbidities or elderly/frail populations. Using adapted consensus-developed frameworks for interventions and outcomes, we have identified the common features of interventions and their overall typology. We suggest these interventions are of value to patients and healthcare systems but require localization and granular evaluation of their components to maximize potential benefits.

Byrne, PJ, Moody, JA, Cooper, S-M, Farrell, E, and Kinsella, S. Short-term effects of "composite training" on strength, jump, and sprint performance in hurling players. J Strength Cond Res 36(8): 2253-2261, 2022-The purpose of this study was to compare the short-term effects of "composite" training to sprint training on strength, jump, and sprint acceleration performance in hurling players. A randomized counterbalanced group design with baseline test, pretest and post-test measures was used. Twenty-five hurling players volunteered to participate and 21 completed the study. Subjects were divided into a "composite" (COMP group, n = 10) or a sprint training (SPRINT group, n = 11) group. Both groups trained twice per week for 7 weeks with the SPRINT group performing 6 repetitions of 20 m sprints and the COMP group completing 6 repetitions (1 repetition = 3 bounce drop jumps [BDJs] with a 20 m sprint after 15 seconds recovery). Significant differences existed pretraining to post-training for the COMP group for BDJ contact time (-7.25%; p = 0.05) and countermovement jump (CMJ) variables (height: 7.43%, p = 0.006; force: 5.24%, p = 0.05; power: 15.11%, p = 0.001). No significant differences were found between groups at baseline and for group by time interactions. Significant improvements were observed pretraining to post-training in both groups for the following: absolute 3 repetition maximum (3RM) back squat strength (12.73-17.62%, p = 0.01), 5 m (5.74-9.49%, p = 0.006-0.04), 10 m (4.27-5.59%, p = 0.007-0.02), and 20 m (3.35-3.98%, p = 0.003-0.01). In conclusion, "composite" training is effective in enhancing fast stretch-shortening cycle efficiency inducing CMJ force and power augmentation. However, "composite" and sprint training are effective training approaches for enhancing maximal strength and sprint performance in a time efficient manner in hurling players.

OBJECTIVE To examine potential relationships between ECG characteristics and echocardiographic measures of cardiac structure in chimpanzees (Pan troglodytes). ANIMALS 341 chimpanzees (175 males and 166 females) from 5 sanctuaries and 2 zoological collections. PROCEDURES Chimpanzees were anesthetized for routine health examinations between May 2011 and July 2017 as part of the International Primate Heart Project and, during the same anesthetic events, underwent 12-lead ECG and transthoracic echocardiographic assessments. Relationships between results for ECG and those for echocardiographic measures of atrial areas, left ventricular internal diameter in diastole (LVIDd), and mean left ventricular wall thicknesses (MLVWT) were assessed with correlational analysis, then multiple linear regression analyses were used to create hierarchical models to predict cardiac structure from ECG findings. RESULTS Findings indicated correlations (r = −0.231 to 0.310) between results for ECG variables and echocardiographic measures. The duration and amplitude of P waves in lead II had the strongest correlations with atrial areas. The Sokolow-Lyon criteria, QRS-complex duration, and R-wave amplitude in leads V6 and II had the strongest correlations with MLVWT, whereas the Sokolow-Lyon criteria, QRS-complex duration, and S-wave amplitude in leads V2 and V1 had the strongest correlations with LVIDd. However, the ECG predictive models that were generated only accounted for 17%, 7%, 11%, and 8% of the variance in the right atrial end-systolic area, left atrial end-systolic area, MLVWT, and LVIDd, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that relationships existed between ECG findings and cardiac morphology in the chimpanzees of the present study; however, further research is required to examine whether the predictive models generated can be modified to improve their clinical utility.

Byrne, PJ, Moody, JA, Cooper, SM, Callanan, D, and Kinsella, S. Potentiating response to drop-jump protocols on sprint acceleration: drop-jump volume and intrarepetition recovery duration. J Strength Cond Res 34(3): 717-727, 2020-The purpose of this study was to investigate the postactivation potentiation response first to bounce drop jump (BDJ) volume; second, BDJ intrarepetition recovery duration and recovery duration between BDJs and 20-meter (including 5- and 10-m split times) sprint performance. The study was undertaken in 2 parts, the first part compared different volumes of BDJs and the second part compared different BDJ intrarepetition recovery periods. The effect of recovery periods between the BDJs and the subsequent 20-m sprints was examined in both parts 1 and 2 (15 seconds, 4, 8, and 12 minutes). Fourteen (mean ± SD: age = 20.83 ± 1.26 years; height = 1.77 ± 0.04 m; and mass = 74.89 ± 6.07 kg) (part 1) and 15 (mean ± SD: age = 20.64 ± 1.00 years; height = 1.78 ± 0.06 m; and mass = 75.67 ± 6.28 kg) (part 2) male collegiate and club hurling players volunteered to participate. A randomized cross-over design was used to compare BDJ volumes (1, 2, and 3 sets of 3 repetitions) and BDJ intrarepetition recovery time (15 vs. 60 seconds) after a warm-up followed by 2 baseline 20-m sprints. The results in part 1 reported a significant improvement in 5- and 10-m sprint time for 1 set of 3 BDJs between baseline and 4 minutes (5 m: -2.34%, p = 0.04, effect size [ES] = -0.043; 10 m: -1.42%, p = 0.03, ES = -0.35), and baseline and 12 minutes (5 m: -3.33%, p = 0.03, ES = -0.57; 10 m: -2.13%, p = 0.01, ES = -0.52). Part 2 reported a significant improvement in 5-m sprint time between baseline and 15 seconds (5 m: -3.38%, p = 0.01, ES = -0.83; 10 m: -2.07%, p = 0.02, ES = -0.58) after the BDJs. The findings support the use of 1 set of 3 BDJs using a 15-second intrarepetition recovery period to maximize 5-, 10-, and 20-m sprint performance after 15 seconds of recovery after the final BDJ in hurling players. The acute response to this BDJ protocol proves to be time efficient and effective in acutely improving sprint acceleration.

Funding The Fold-Thrust Research Group has been funded by InterOil, Santos, OilSearch and NAGRA. The original compilation of Cadell’s researches was part of an outreach programme funded by BP. Acknowledgements RWHB is indebted to the late John Mendum for arranging access to Cadell’s notebooks and his field maps that were lodged in the then offices of the British Geological Survey in Murchison House, Edinburgh. This formed part of a collaboration with BGS and the development of the “Assynt’s Geology” website in the early 2000s. Many of the images from Cadell’s notebooks, including his experimental results, were part of this site. Regrettably it has not been maintained and is no longer accessible. Rectifying this loss of resource forms the motivation for this contribution. We thank Juergen Adam and an anonymous referee for construct reviews, together with James Hammerstein for shepherding the manuscript through the editing process, although of course the views expressed in this paper remain the responsibility of the authors alone.

Hyperkalemia after starting renin-angiotensin system inhibitors has been shown to be subsequently associated with a higher risk of cardiovascular and kidney outcomes. However, whether to continue or discontinue the drug after hyperkalemia remains unclear.Data came from the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial, which included a run-in period where all participants initiated angiotensin-converting enzyme inhibitor-based therapy (a fixed combination of perindopril and indapamide). The study population was taken as patients with type 2 diabetes with normokalemia (serum potassium of 3.5 to5.0 mEq/L) at the start of run-in. Potassium was remeasured 3 weeks later when a total of 9694 participants were classified into hyperkalemia (≥5.0 mEq/L), normokalemia, and hypokalemia (3.5 mEq/L) groups. After run-in, patients were randomized to continuation of the angiotensin-converting enzyme inhibitor-based therapy or placebo; major macrovascular, microvascular, and mortality outcomes were analyzed using Cox regression during the following 4.4 years (median).During active run-in, 556 (6%) participants experienced hyperkalemia. During follow-up, 1505 participants experienced the primary composite outcome of major macrovascular and microvascular events. Randomized treatment of angiotensin-converting enzyme inhibitor-based therapy significantly decreased the risk of the primary outcome (38.1 versus 42.0 per 1000 person-years; hazard ratio, 0.91; 95% confidence interval, 0.83 to 1.00;Continuation of angiotensin-converting enzyme inhibitor-based therapy consistently decreased the subsequent risk of clinical outcomes, including cardiovascular and kidney outcomes and death, regardless of short-term changes in serum potassium.Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE), NCT00145925.

Global food security requires food production to be increased in the coming decades. The closure of any existing genetic yield gap (Yig) by genetic improvement could increase crop yield potential and global production. Here we estimated present global wheat Yig, covering all wheat-growing environments and major producers, by optimizing local wheat cultivars using the wheat model Sirius. The estimated mean global Yig was 51%, implying that global wheat production could benefit greatly from exploiting the untapped global Yig through the use of optimal cultivar designs, utilization of the vast variation available in wheat genetic resources, application of modern advanced breeding tools, and continuous improvements of crop and soil management.

Predictive breeding is now widely practised in crop improvement programmes and has accelerated selection response (i.e. the amount of genetic gain between breeding cycles) for complex traits. However, world food production needs to increase further to meet the demands of the growing human population. The prediction of complex traits with current methods can be inconsistent across different genetic, environmental and agronomic management contexts because the complex relationships between genomic and phenotypic variation are not well accounted for. Therefore, developing gene-to-phenotype network models for traits that integrate the knowledge of networks from systems biology, plant and crop physiology with population genomics has been proposed to close this gap in predictive modelling. Here, we develop a gene-to-phenotype network for shoot branching, a critical developmental pathway underpinning harvestable yield for many crop species, as a case study to explore the value of developing gene-to-phenotype networks to enhance understanding of selection responses. We observed that genetic canalization is an emergent property of the complex interactions among shoot branching gene-to-phenotype network components, leading to the accumulation of cryptic genetic variation, reduced selection responses and large variation in selection trajectories across populations. As genetic canalization is expected to be pervasive in traits, such as grain yield, that result from interactions among multiple genes, traits, environments and agronomic management practices, the need to model traits in crop improvement programmes as outcomes of gene-to-phenotype networks is highlighted as an emerging opportunity to advance our understanding of selection response and the efficiency of developing resilient crops for future climates.

Purpose: Problematic polypharmacy can exaggerate “medicine burden” for the patient. Patient-reported outcomes (PROs) are key indicators of medicine burden, and PRO measures (PROMs) can help patients articulate their perceptions of medicine burden. We aimed to: (a) evaluate what PROMs currently exist that assess medicine burden, and what PROs they target, and (b) understand patients’ experiences with using multiple medicines to establish a core set of most meaningful and relevant PROs for assessment in polypharmacy medicines reviews. Patients and Methods: We conducted a prospective, sequential mixed-methods study in two consecutive work phases. Phase 1 involved a rapid review of PROMs, informed by the published PRISMA and COSMIN initiative guidelines. We integrated all evidence in a thematic narrative synthesis. Phase 2 involved cross-sectional, one-to-one, semi-structured interviews with key stakeholders, including members of the public and healthcare professionals (HCPs). We conducted thematic content analysis to identify and classify emerging PROs. Results: In Phase 1, 13 studies described the development and/or validation of 12 PROMs. The PROMs targeted 14 content domains of adult patients’ experiences with prescribed medicines. PROMs varied widely in terms of length, comprehensiveness and psychometric robustness. In Phase 2, all participants (seven members of the public; eight HCPs) agreed on the clinical relevance of PROMs, providing a rich account of justifications. We identified four core PROs: ‘Knowledge, information and communication about own medicines’; “Perceptions, views and attitudes about (own) medicines”; “Impact on daily living: Side-effects and practicalities”, and “Medicine usage: ‘as planned’, misuse, abuse, no use”. Conclusion: We suggest combining psychometrically robust PROMs or domains across PROMs into a bespoke PROM that addresses comprehensively and succinctly the four core PROs. We recommend a careful implementation process that must involve consultation with all relevant stakeholders, while establishing a clear purpose for collecting a PROM and realistic and ongoing collection at key time-points.

Aim: \ud This study aimed to identify, evaluate and summarise current evidence in relation to the factors that influence the conducting of research by nurses in clinical practice.\ud \ud Design: \ud This study used mixed methods systematic review.\ud \ud Data sources: \ud CINAHL, EMBASE, MEDLINE, Scopus and ASSIA, with dates limited from 2015 to 2020, were used to conduct a systematic search of the literature.\ud \ud Review methods: \ud The Joanna Briggs Institute approach was followed, with results reported according to the Preferred Reporting System for Systematic Reviews and Meta-Analyses. The associated checklist for systematic reviews was also used. A standardised data extraction tool was then used, with quality appraisal guided by the Mixed Methods Appraisal Tool, with a subsequent convergent qualitative synthesis.\ud \ud Results: \ud Sixteen papers were identified for inclusion, nine quantitative, six qualitative and one mixed methods. Four themes were identified: research competence and culture, proactive research mentorship, research resources and making a difference. These were critically discussed in relation to barriers and enablers to the conduct of research by nurses in clinical practice. Commonly cited barriers included a lack of research knowledge, confidence and access to resources, particularly protected time, while enablers such as educational partnerships, identifying research-motivated clinical nurses and access to research role models were also apparent in the literature.\ud \ud Conclusions: \ud Globally, nurses in clinical practice are clearly motivated to engage in the research process despite apparent barriers that have a significant impact on productivity. Nevertheless, there are also enablers to building research capacity apparent that offer methodological and structural approaches to empower this group to conduct research.

Alzheimer’s disease (AD) is a neurodegenerative disorder, accounting for at least two-thirds of dementia cases. A combination of genetic, epigenetic and environmental triggers is widely accepted to be responsible for the onset and development of AD. Accumulating evidence shows that oxidative stress and dysregulation of energy metabolism play an important role in AD pathogenesis, leading to neuronal dysfunction and death. Redox-induced protein modifications have been reported in the brain of AD patients, indicating excessive oxidative damage. Coenzyme A (CoA) is essential for diverse metabolic pathways, regulation of gene expression and biosynthesis of neurotransmitters. Dysregulation of CoA biosynthesis in animal models and inborn mutations in human genes involved in the CoA biosynthetic pathway have been associated with neurodegeneration. Recent studies have uncovered the antioxidant function of CoA, involving covalent protein modification by this cofactor (CoAlation) in cellular response to oxidative or metabolic stress. Protein CoAlation has been shown to both modulate the activity of modified proteins and protect cysteine residues from irreversible overoxidation. In this study, immunohistochemistry analysis with highly specific anti-CoA monoclonal antibody was used to reveal protein CoAlation across numerous neurodegenerative diseases, which appeared particularly frequent in AD. Furthermore, protein CoAlation consistently co-localized with tau-positive neurofibrillary tangles, underpinning one of the key pathological hallmarks of AD. Double immunihistochemical staining with tau and CoA antibodies in AD brain tissue revealed co-localization of the two immunoreactive signals. Further, recombinant 2N3R and 2N4R tau isoforms were found to be CoAlated in vitro and the site of CoAlation mapped by mass spectrometry to conserved cysteine 322, located in the microtubule binding region. We also report the reversible H2O2-induced dimerization of recombinant 2N3R, which is inhibited by CoAlation. Moreover, CoAlation of transiently expressed 2N4R tau was observed in diamide-treated HEK293/Pank1β cells. Taken together, this study demonstrates for the first time extensive anti-CoA immunoreactivity in AD brain samples, which occurs in structures resembling neurofibrillary tangles and neuropil threads. Covalent modification of recombinant tau at cysteine 322 suggests that CoAlation may play an important role in protecting redox-sensitive tau cysteine from irreversible overoxidation and may modulate its acetyltransferase activity and functional interactions.

The Canadian Federation of Earth Sciences (CFES) has issued this statement to summarize the science, effects, and implications of climate change. We highlight the role of Earth scientists in documenting and mitigating climate change, and in managing and adapting to its consequences in Canada. CFES is the coordinated voice of Canada’s Earth Sciences community with 14 member organizations representing some 15,000 geoscientists. Our members are drawn from academia, industry, education, and government. The mission of CFES is to ensure decision makers and the public understand the contributions of Earth Science to Canadian society and the economy.Climate change has become a national and global priority for all levels of government. The geological record shows us that the global climate has changed throughout Earth’s history, but the current rates of change are almost unprecedented. Over the last 70 years, levels of common greenhouse gases (GHGs) in the atmosphere have steadily increased. Carbon dioxide (CO2) concentration is now 418 parts per million — its highest of the last three million years. The chemical (isotopic) composition of carbon in the atmosphere indicates the increase in GHGs is due to burning fossil fuels. GHGs absorb energy emitted from Earth’s surface and re-radiate it back, warming the lower levels of the atmosphere. Climatic adjustments that have recently occurred are, in practical terms, irreversible, but further change can be mitigated by lowering emissions of GHGs.Climate change is amplified by three important Earth system processes and effects. First, as the climate warms evaporation increases, raising atmospheric concentrations of water vapour, itself a GHG — and adding to warming. Second, loss of ice cover from the polar ice sheets and glaciers exposes larger areas of land and open water — leading to greater absorption of heat from the sun. Third, thawing of near-surface permafrost releases additional GHGs (primarily CO2 and methane) during decay of organic matter previously preserved frozen in the ground. Some impacts of climate change are incremental and steadily occurring, such as melting of glaciers and ice sheets, with consequent sea level rise. Others are intermittent, such as extreme weather events, like hurricanes — but are becoming more frequent. Summer water shortages are increasingly common in western Canada as mountain snowpacks melt earlier and summer river flows decline. In northern Canada, warming and thawing of near-surface permafrost has led to deterioration of infrastructure and increased costs for buildings that now require chilled foundations. Other consequences of unchecked climate change include increased coastal erosion, increases in the number and size of wildfires, and reduction in winter road access to isolated northern communities. Reductions in net GHG emissions are urgently required to mitigate the many effects of further climate change. Industrial and public works development projects must now assess the effects of climate change in their planning, design, and management. Cities, municipalities, and rural communities need to plan new residential development carefully to avoid enhanced risk of flooding, coastal erosion, or wildfire.Earth Science knowledge and expertise is integral to exploration and development of new metals and Earth materials required for a carbon-neutral future, and in the capture and storage of CO2 within the Earth. Earth Science is also central to society’s adaptation to new climatic regimes and reduction of risks. This includes anticipation, assessment, and management of extreme events, development of new standards and guidelines for geotechnical and engineering practice, and revision to regulations that consider climate change. Geoscientists also have an important role in the education of students and the public on the reasons for necessary action. Canada is uniquely positioned with its strong global geoscientific leadership, its vast landmass, and its northern terrain to effectively leverage research activities around climate change. Geoscience tools and geoscientists’ skills will be integral to Canada’s preparation for climate change., La Fédération canadienne des sciences de la Terre (FCST) a publié ce communiqué pour résumer la science, les effets et les implications des changements climatiques. Nous soulignons le rôle des scientifiques en science de la Terre dans la documentation et l'atténuation des changements climatiques, ainsi que dans la gestion de leurs conséquences et la création de mesures d'adaptation au Canada. La FCST est la voix coordonnée de la communauté canadienne des sciences de la Terre avec 14 organisations membres représentant environ 15 000 géoscientifiques. Nos membres sont issus du milieu universitaire, de l'industrie, de l'éducation et du gouvernement. La mission de la FCST est de s'assurer que les décideurs et le public comprennent les contributions des sciences de la Terre à la société canadienne et à l'économie.Les changements climatiques sont devenus une priorité nationale et mondiale à tous les niveaux de gouvernement. Les archives géologiques nous montrent que le climat mondial a changé tout au long de l'histoire de la Terre, mais les taux de changement actuels sont presque sans précédent. Au cours des 70 dernières années, les niveaux de gaz à effet de serre (GES) communs dans l'atmosphère n'ont cessé d'augmenter. La concentration de dioxyde de carbone (CO2) est maintenant de 418 parties par million - son plus haut niveau des trois derniers millions d'années. La composition chimique (isotopique) du carbone dans l'atmosphère indique que l'augmentation des GES est due à la combustion de combustibles fossiles. Les GES absorbent l'énergie émise par la surface de la Terre et la réfléchissent, réchauffant les niveaux inférieurs de l'atmosphère. Les modifications climatiques qui se sont produits récemment sont, concrètement, irréversibles, mais les changements additionnels peuvent être atténués en réduisant les émissions de GES.Les changements climatiques sont amplifiés par trois processus et effets importants du système terrestre. Premièrement, à mesure que le climat se réchauffe, l'évaporation augmente, ce qui augmente les concentrations atmosphériques de vapeur d'eau, elle-même un GES, et contribue au réchauffement. Deuxièmement, la perte de la couverture de glace des calottes glaciaires polaires et des glaciers expose de plus grandes superficies de terre et d'eau libre, ce qui entraîne une plus grande absorption de la chaleur du soleil. Troisièmement, le dégel du pergélisol proche de la surface libère des GES supplémentaires (principalement du CO2 et du méthane) lors de la décomposition de la matière organique jusqu’alors préservée gelée dans le sol. Certains impacts des changements climatiques sont progressifs et se produisent régulièrement, comme la fonte des glaciers et des calottes glaciaires, avec pour conséquence une élévation du niveau de la mer. D'autres sont intermittents, comme les événements météorologiques extrêmes, tels que les ouragans, mais deviennent de plus en plus fréquents. Les pénuries d'eau en été sont de plus en plus courantes dans l'ouest du Canada, car le manteau neigeux des montagnes fond plus tôt et le débit des rivières en été diminue. Dans le nord du Canada, le réchauffement et le dégel du pergélisol proche de la surface ont entraîné une détérioration des infrastructures et une augmentation des coûts des bâtiments qui nécessitent maintenant des fondations réfrigérées. Les autres conséquences des changements climatiques incontrôlés comprennent l'augmentation de l'érosion côtière, l'augmentation du nombre et de la taille des incendies de forêt et la réduction de l'accès aux routes d’hiver aux collectivités isolées du Nord. Des réductions des émissions nettes de GES sont nécessaires de toute urgence pour atténuer les nombreux effets de nouveaux changements climatiques. Les projets de développement industriel et de travaux publics doivent désormais évaluer les effets des changements climatiques dans leur planification, leur conception et leur gestion. Les villes, les municipalités et les communautés rurales doivent planifier soigneusement les nouveaux développements résidentiels pour éviter les risques accrus d'inondation, d'érosion côtière ou d'incendie de forêt.Les connaissances et l'expertise en sciences de la Terre font partie intégrante de l'exploration et du développement de nouveaux métaux et matériaux terrestres requis pour un avenir neutre en carbone, ainsi que dans la capture et la séquestration du CO2 dans la Terre. Les sciences de la Terre sont également au cœur de l'adaptation de la société aux nouveaux régimes climatiques et de la réduction des risques. Cela comprend l'anticipation, l'évaluation et la gestion des événements extrêmes, l'élaboration de nouvelles normes et directives pour les pratiques géotechniques et d'ingénierie, et la révision des réglementations qui tient compte des changements climatiques. Les géoscientifiques ont également un rôle important dans l'éducation des étudiants et du public sur le fondement des mesures nécessaires. Le Canada occupe une position unique grâce à son solide leadership géoscientifique mondial, sa vaste étendue et son territoire nordique pour tirer efficacement parti des activités de recherche sur les changements climatiques. Les outils géoscientifiques et les compétences des géoscientifiques feront partie intégrante de la préparation du Canada aux changements climatiques.