Sensitivity of ocean circulation to warming during the Early Eocene greenhouse.

Multiple abrupt warming events ("hyperthermals") punctuated the Early Eocene and were associated with deep-sea temperature increases of 2 to 4 °C, seafloor carbonate dissolution, and negative carbon isotope (δ13C) excursions. Whether hyperthermals were associated with changes in the global ocean overturning circulation is important for understanding their driving mechanisms and feedbacks and for gaining insight into the circulation's sensitivity to climatic warming. Here, we present high-resolution benthic foraminiferal stable isotope records (δ13C and δ18O) throughout the Early Eocene Climate Optimum (~53.26 to 49.14 Ma) from the deep equatorial and North Atlantic. Combined with existing records from the South Atlantic and Pacific, these indicate consistently amplified δ13C excursion sizes during hyperthermals in the deep equatorial Atlantic. We compare these observations with results from an intermediate complexity Earth system model to demonstrate that this spatial pattern of δ13C excursion size is a predictable consequence of global warming-induced changes in ocean overturning circulation. In our model, transient warming drives the weakening of Southern Ocean-sourced overturning circulation, strengthens Atlantic meridional water mass aging gradients, and amplifies the magnitude of negative δ13C excursions in the equatorial to North Atlantic. Based on model-data consistency, we conclude that Eocene hyperthermals coincided with repeated weakening of the global overturning circulation. Not accounting for ocean circulation impacts on δ13C excursions will lead to incorrect estimates of the magnitude of carbon release driving hyperthermals. Our finding of weakening overturning in response to past transient climatic warming is consistent with predictions of declining Atlantic Ocean overturning strength in our warm future.

Very large release of mostly volcanic carbon during the Palaeocene-Eocene Thermal Maximum.

The Palaeocene-Eocene Thermal Maximum (PETM) was a global warming event that occurred about 56 million years ago, and is commonly thought to have been driven primarily by the destabilization of carbon from surface sedimentary reservoirs such as methane hydrates. However, it remains controversial whether such reservoirs were indeed the source of the carbon that drove the warming. Resolving this issue is key to understanding the proximal cause of the warming, and to quantifying the roles of triggers versus feedbacks. Here we present boron isotope data-a proxy for seawater pH-that show that the ocean surface pH was persistently low during the PETM. We combine our pH data with a paired carbon isotope record in an Earth system model in order to reconstruct the unfolding carbon-cycle dynamics during the event. We find strong evidence for a much larger (more than 10,000 petagrams)-and, on average, isotopically heavier-carbon source than considered previously. This leads us to identify volcanism associated with the North Atlantic Igneous Province, rather than carbon from a surface reservoir, as the main driver of the PETM. This finding implies that climate-driven amplification of organic carbon feedbacks probably played only a minor part in driving the event. However, we find that enhanced burial of organic matter seems to have been important in eventually sequestering the released carbon and accelerating the recovery of the Earth system.

The VISA-A (sedentary) should be used for sedentary patients with Achilles tendinopathy: a modified version of the VISA-A developed and evaluated in accordance with the COSMIN checklist.

OBJECTIVE: To develop and evaluate a modified version of the Victorian Institute of Sport Assessment-Achilles (VISA-A) questionnaire, for use in sedentary patients with Achilles tendinopathy, using the Consensus-based Standards for the selection of health Measurement Instruments recommendations. METHODS: Twenty-two sedentary patients with Achilles tendinopathy completed the VISA-A and provided feedback regarding the relevance, comprehensiveness and comprehensibility of each item, response options and instructions. Patient and professional feedback was used to develop the VISA-A (sedentary) questionnaire. Reliability, validity and responsiveness of the VISA-A (sedentary) was evaluated in 51 sedentary patients with Achilles tendinopathy: 47.1% women, mean age 64.8 (SD 11.24). RESULTS: Factor analysis identified two dimensions (symptoms and activity) for the VISA-A (sedentary). Test-retest reliability was excellent for symptoms (intraclass correlation coefficient, ICC=0.991) and activity (ICC=0.999). Repeatability was 1.647 for symptoms and 0.549 for activity. There was a significant difference between the VISA-A and VISA-A (sedentary) scores both pretreatment and post-treatment. There was stronger correlation between the pretreatment to post-treatment change in the VISA-A (sedentary) scores (r=0.420 for symptoms, r=0.407 for activity) and the global rating of change than the VISA-A scores (r=0.253 for symptoms, r=0.186 for activity). CONCLUSION: The VISA-A (sedentary) demonstrates adequate reliability, validity and responsiveness in sedentary patients with Achilles tendinopathy. The VISA-A (sedentary) is a more appropriate measure than the VISA-A for this cohort and is recommended for clinical and research purposes.

The diagnostic accuracy of clinical tests for anterior cruciate ligament tears are comparable but the Lachman test has been previously overestimated: a systematic review and meta-analysis.

PURPOSE: The diagnostic accuracy of clinical tests for anterior cruciate ligament injury has been reported in previous systematic reviews. Numerous studies in these reviews include subjects with additional knee ligament injury, which could affect the sensitivity of the tests. Meta-analyses have also been performed using methods that do not account for the non-independence of sensitivity and specificity, potentially overestimating diagnostic accuracy. The aim of this study was to report the diagnostic accuracy of clinical tests for anterior cruciate ligament tears (partial and complete) without concomitant knee ligament injury. METHODS: A systematic review with meta-analysis was performed according to the PRISMA guidelines. Meta-analyses included studies reporting the specificity and/or sensitivity of tests with or without concomitant meniscal injury. Where possible, pooled diagnostic estimates were calculated with bivariate random-effects modelling to determine the most accurate effect sizes. Diagnostic accuracy values are presented for the anterior drawer, Lachman, Lever sign and pivot shift tests overall and in acute or post-acute presentations. RESULTS: Pooled estimates using a bivariate model for overall sensitivity and specificity respectively were as follows: anterior drawer test 83% [95% CI, 77-88] and 85% [95% CI, 64-95]; Lachman test 81% [95% CI, 73-87] and 85% [95% CI, 73-92]; pivot shift test 55% [95% CI, 47-62] and 94% [95% CI, 88-97]; Lever sign test 83% [95% CI, 68-92] and 91% [95% CI, 83-95]. For specific presentations, the sensitivity and specificity of the Lachman test, respectively, were: complete tears 68% [95% CI, 54-79] and 79% [95% CI, 51-93]; post-acute injuries 70% [95% CI, 57-80] and 77% [95% CI, 53-91]. CONCLUSIONS: The pivot shift and Lever sign were the best tests overall for ruling in or ruling out an anterior cruciate ligament tear, respectively. The diagnostic accuracy of the Lachman test, particularly in post-acute presentations and for complete tears, is lower than previously reported. Further research is required to establish more accurate estimates for the Lachman test in acute presentations and partial ligament tears using bivariate analysis. LEVEL OF EVIDENCE: III.

Endoscopic features of buried Barrett's mucosa.

BACKGROUND AND AIMS: Buried Barrett's mucosa is defined as intestinal metaplasia that is "buried" under the normal-appearing squamous epithelium. This can occur in Barrett's esophagus with or without previous endoscopic therapy. Dysplasia and neoplasia within buried Barrett's mucosa have also been reported. However, endoscopic features of buried Barrett's mucosa have not been described. At our tertiary referral center for Barrett's esophagus, several endoscopic features have been observed in patients who were found to have buried Barrett's mucosa on histology. These features are squamous epithelium which is (1) darker pink on white-light and darker brown on narrow-band imaging and/or (2) has a slightly raised or nodular appearance. It was also observed that either of these 2 features is frequently seen adjacent to a Barrett's mucosa island. This study aimed to (1) evaluate the diagnostic accuracy of these endoscopic features, and (2) evaluate the frequency of endoscopically identifiable buried Barrett's mucosa in patients with dysplastic Barrett's esophagus, before and after endoscopic eradication therapy. METHODS: This was a retrospective analysis of a prospectively observed cohort of all cases of dysplastic Barrett's esophagus referred to St Vincent's Hospital, Melbourne. Endoscopy documentation software and histopathology reports of esophageal biopsy and EMR specimens between March 2013 and March 2019 were searched for terms "buried" or "subsquamous" Barrett's mucosa. Endoscopic reports, images, and histopathology reports of suspected buried Barrett's mucosa were then reviewed to apply the endoscopic features and correlate with the histologic diagnosis. RESULTS: In a cohort of 506 patients with dysplastic Barrett's esophagus, 33 (7%) patients (73% male, median age at referral 70.5 years) had buried Barrett's mucosa on histology. Twenty-seven (82%) patients had previous treatment for dysplastic Barrett's esophagus; radiofrequency in 2 (6%), EMR in 4 (12%), and both modalities in 21 (64%). Six (18%) had no previous treatment. Histologically confirmed buried Barrett's mucosa was suspected at endoscopy in 26 patients (79%). Endoscopic features were (1) darker pink or darker brown mucosa underneath squamous epithelium (24%), (2) raised areas underneath squamous mucosa (27%), and both features present concurrently (27%). These features were associated with adjacent islands of Barrett's esophagus in 48%. Forty-four cases of buried Barrett's mucosa were suspected endoscopically, and these were sampled by biopsy (50%) and EMR (50%). Buried Barrett's mucosa was confirmed in 26 cases, with a positive predictive value of endoscopic suspicion of 59%. Eighteen cases of endoscopically suspected buried Barrett's mucosa had no buried Barrett's mucosa on histology; inflammation or reflux was identified in 12 (67%) patients. Dysplasia was identified within buried Barrett's mucosa in 12 (36%) patients; 5 intramucosal adenocarcinoma, 1 high-grade dysplasia, and 6 low-grade dysplasia. Endoscopic features of buried Barrett's mucosa were observed in 11 of 12 cases harboring dysplasia or neoplasia, compared with 15 of 21 cases of buried Barrett's mucosa without dysplasia. CONCLUSIONS: In this retrospective analysis of prospectively observed patients with dysplastic Barrett's esophagus, buried Barrett's mucosa was identified in 7%, including treatment-naive patients. The proposed endoscopic features of buried Barrett's mucosa were seen in 79% of patients with histology confirmed disease. These endoscopic features may predict the presence of buried Barrett's mucosa, which may contain dysplasia or neoplasia. An overlap between the endoscopic features of inflammation, reflux, and buried Barrett's mucosa was observed. Future prospective studies are required to develop and validate endoscopic criteria for identifying buried Barrett's mucosa.

Barrett's esophagus with low-grade dysplasia: high rate of upstaging at Barrett's esophagus referral units suggests progression rates may be overestimated.

BACKGROUND AND AIMS: The reported progression rate from low-grade dysplasia (LGD) in Barrett's esophagus (BE) to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) ranges from .4% to 13.4% per year. We hypothesize that some reported progression rates may be overestimated because of prevalent HGD or EAC that was not identified during endoscopic assessments performed in the community. Our aim is to determine the proportion of prevalent HGD or EAC detected by BE referral units (BERUs) in patients referred from the community with a recent diagnosis of LGD. METHODS: All patients referred from the community to 6 BERUs with a diagnosis of BE with LGD were identified. Patients with an assessment endoscopy performed at BERUs more than 6 months from their referral endoscopy in the community were excluded. Visible lesions and histology outcomes were compared between the community referral endoscopy and the assessment endoscopy performed at BERUs. RESULTS: The median time between BERU assessment and referral endoscopy was 79 days (interquartile range, 54-114). Of the 75 patients referred from the community with LGD, BERU assessment identified HGD or EAC in 20 patients (27%). BERU assessment identified more visible lesions than referral endoscopy performed in the community (39 [52%] vs 9 [12%], respectively; P = .029). CONCLUSIONS: BERU assessment endoscopy identified more visible lesions than community referral endoscopy and identified HGD or EAC in 27% of patients referred from the community with a recent diagnosis of LGD. Reported progression rates from LGD to HGD or EAC may be overestimated.

Two pulses of morphological diversification in Pacific pelagic fishes following the Cretaceous-Palaeogene mass extinction.

Molecular phylogenies suggest some major radiations of open-ocean fish clades occurred roughly coincident with the Cretaceous-Palaeogene (K/Pg) boundary, however the timing and nature of this diversification is poorly constrained. Here, we investigate evolutionary patterns in ray-finned fishes across the K/Pg mass extinction 66 million years ago (Ma), using microfossils (isolated teeth) preserved in a South Pacific sediment core spanning 72-43 Ma. Our record does not show significant turnover of fish tooth morphotypes at the K/Pg boundary: only two of 48 Cretaceous tooth morphotypes disappear at the event in the South Pacific, a rate no different from background extinction. Capture-mark-recapture analysis finds two pulses of origination in fish tooth morphotypes following the mass extinction. The first pulse, at approximately 64 Ma, included short-lived teeth, as well as forms that contribute to an expansion into novel morphospace. A second pulse, centred at approximately 58 Ma, produced morphotype novelty in a different region of morphospace from the first pulse, and contributed significantly to Eocene tooth morphospace occupation. There was no significant increase in origination rates or expansion into novel morphospace during the early or middle Eocene, despite a near 10-fold increase in tooth abundance during that interval. Our results suggest that while the K/Pg event had a minor impact on fish diversity in terms of extinction, the removal of the few dominant Cretaceous morphotypes triggered a sequence of origination events allowing fishes to rapidly diversify morphologically, setting the stage for exceptional levels of ray-finned fish diversity in the Cenozoic.

New Age of Fishes initiated by the Cretaceous-Paleogene mass extinction.

Ray-finned fishes (Actinopterygii) comprise nearly half of all modern vertebrate diversity, and are an ecologically and numerically dominant megafauna in most aquatic environments. Crown teleost fishes diversified relatively recently, during the Late Cretaceous and early Paleogene, although the exact timing and cause of their radiation and rise to ecological dominance is poorly constrained. Here we use microfossil teeth and shark dermal scales (ichthyoliths) preserved in deep-sea sediments to study the changes in the pelagic fish community in the latest Cretaceous and early Paleogene. We find that the Cretaceous-Paleogene (K/Pg) extinction event marked a profound change in the structure of ichthyolith communities around the globe: Whereas shark denticles outnumber ray-finned fish teeth in Cretaceous deep-sea sediments around the world, there is a dramatic increase in the proportion of ray-finned fish teeth to shark denticles in the Paleocene. There is also an increase in size and numerical abundance of ray-finned fish teeth at the boundary. These changes are sustained through at least the first 24 million years of the Cenozoic. This new fish community structure began at the K/Pg mass extinction, suggesting the extinction event played an important role in initiating the modern "age of fishes."

Eocene global warming events driven by ventilation of oceanic dissolved organic carbon.

'Hyperthermals' are intervals of rapid, pronounced global warming known from six episodes within the Palaeocene and Eocene epochs (∼65-34 million years (Myr) ago). The most extreme hyperthermal was the ∼170 thousand year (kyr) interval of 5-7 °C global warming during the Palaeocene-Eocene Thermal Maximum (PETM, 56 Myr ago). The PETM is widely attributed to massive release of greenhouse gases from buried sedimentary carbon reservoirs, and other, comparatively modest, hyperthermals have also been linked to the release of sedimentary carbon. Here we show, using new 2.4-Myr-long Eocene deep ocean records, that the comparatively modest hyperthermals are much more numerous than previously documented, paced by the eccentricity of Earth's orbit and have shorter durations (∼40 kyr) and more rapid recovery phases than the PETM. These findings point to the operation of fundamentally different forcing and feedback mechanisms than for the PETM, involving redistribution of carbon among Earth's readily exchangeable surface reservoirs rather than carbon exhumation from, and subsequent burial back into, the sedimentary reservoir. Specifically, we interpret our records to indicate repeated, large-scale releases of dissolved organic carbon (at least 1,600 gigatonnes) from the ocean by ventilation (strengthened oxidation) of the ocean interior. The rapid recovery of the carbon cycle following each Eocene hyperthermal strongly suggests that carbon was re-sequestered by the ocean, rather than the much slower process of silicate rock weathering proposed for the PETM. Our findings suggest that these pronounced climate warming events were driven not by repeated releases of carbon from buried sedimentary sources, but, rather, by patterns of surficial carbon redistribution familiar from younger intervals of Earth history.

Eighty-five million years of Pacific Ocean gyre ecosystem structure: long-term stability marked by punctuated change.

While the history of taxonomic diversification in open ocean lineages of ray-finned fish and elasmobranchs is increasingly known, the evolution of their roles within the open ocean ecosystem remains poorly understood. To assess the relative importance of these groups through time, we measured the accumulation rate of microfossil fish teeth and elasmobranch dermal denticles (ichthyoliths) in deep-sea sediment cores from the North and South Pacific gyres over the past 85 million years (Myr). We find three distinct and stable open ocean ecosystem structures, each defined by the relative and absolute abundance of elasmobranch and ray-finned fish remains. The Cretaceous Ocean (pre-66 Ma) was characterized by abundant elasmobranch denticles, but low abundances of fish teeth. The Palaeogene Ocean (66-20 Ma), initiated by the Cretaceous/Palaeogene mass extinction, had nearly four times the abundance of fish teeth compared with elasmobranch denticles. This Palaeogene Ocean structure remained stable during the Eocene greenhouse (50 Ma) and the Eocene-Oligocene glaciation (34 Ma), despite large changes in the overall accumulation of both groups during those intervals, suggesting that climate change is not a primary driver of ecosystem structure. Dermal denticles virtually disappeared from open ocean ichthyolith assemblages approximately 20 Ma, while fish tooth accumulation increased dramatically in variability, marking the beginning of the Modern Ocean. Together, these results suggest that open ocean fish community structure is stable on long timescales, independent of total production and climate change. The timing of the abrupt transitions between these states suggests that the transitions may be due to interactions with other, non-preserved pelagic consumer groups.

Patient-specific computational models predict prognosis in B cell lymphoma by quantifying pro-proliferative and anti-apoptotic signatures from genetic sequencing data.

Genetic heterogeneity and co-occurring driver mutations impact clinical outcomes in blood cancers, but predicting the emergent effect of co-occurring mutations that impact multiple complex and interacting signalling networks is challenging. Here, we used mathematical models to predict the impact of co-occurring mutations on cellular signalling and cell fates in diffuse large B cell lymphoma and multiple myeloma. Simulations predicted adverse impact on clinical prognosis when combinations of mutations induced both anti-apoptotic (AA) and pro-proliferative (PP) signalling. We integrated patient-specific mutational profiles into personalised lymphoma models, and identified patients characterised by simultaneous upregulation of anti-apoptotic and pro-proliferative (AAPP) signalling in all genomic and cell-of-origin classifications (8-25% of patients). In a discovery cohort and two validation cohorts, patients with upregulation of neither, one (AA or PP), or both (AAPP) signalling states had good, intermediate and poor prognosis respectively. Combining AAPP signalling with genetic or clinical prognostic predictors reliably stratified patients into striking prognostic categories. AAPP patients in poor prognosis genetic clusters had 7.8 months median overall survival, while patients lacking both features had 90% overall survival at 120 months in a validation cohort. Personalised computational models enable identification of novel risk-stratified patient subgroups, providing a valuable tool for future risk-adapted clinical trials.

Inline dynamometry provides reliable measurements of quadriceps strength in healthy and ACL-reconstructed individuals and is a valid substitute for isometric electromechanical dynamometry following ACL reconstruction.

BACKGROUND: Quadriceps strength testing is recommended to guide rehabilitation and mitigate the risk of second injury following anterior cruciate ligament (ACL) reconstruction. Hand-held dynamometry is a practical alternative to electromechanical dynamometry but demonstrates insufficient reliability and criterion validity in healthy and ACL-reconstructed participants respectively. The purpose of this study is to investigate the reliability and concurrent validity of inline dynamometry for measuring quadriceps strength. The hypotheses are that intra-class correlation coefficient (ICC) values will be >0.90 for reliability and concurrent validity. METHODS: This was a cross sectional study using a within-participant, repeated measures design. Isometric quadriceps testing was performed at 60° knee flexion in 50 healthy and 52 ACL-reconstructed participants. Interrater reliability, intrarater reliability, and concurrent validity of inline dynamometry was investigated through calculation of ICCs, Bland-Altman analysis, linear regression, standard error of measurement (SEM) and minimal detectable change (MDC). RESULTS: The lower bounds of the 95% confidence intervals were >0.90 for all reliability and validity ICCs in healthy and ACL-reconstructed participants, except for intrarater reliability in healthy participants using absolute scores (ICC = 0.936 [95% CI 0.890-0.963]). In ACL-reconstructed participants, Bland-Altman bias was 0.01 Nm/kg for absolute and average scores, limits of agreement were -11.74% to 12.59% for absolute scores, the SEM was 0.13Nm/kg (95% CI 0.10-0.17) and the MDC was 0.36Nm/kg (95% CI 0.28 - 0.47). CONCLUSION: Inline dynamometry is a reliable and economical alternative to electromechanical dynamometry for the assessment of quadriceps strength following ACL-reconstruction. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT05109871).

Oxygen rise in the tropical upper ocean during the Paleocene-Eocene Thermal Maximum.

The global ocean's oxygen inventory is declining in response to global warming, but the future of the low-oxygen tropics is uncertain. We report new evidence for tropical oxygenation during the Paleocene-Eocene Thermal Maximum (PETM), a warming event that serves as a geologic analog to anthropogenic warming. Foraminifera-bound nitrogen isotopes indicate that the tropical North Pacific oxygen-deficient zone contracted during the PETM. A concomitant increase in foraminifera size implies that oxygen availability rose in the shallow subsurface throughout the tropical North Pacific. These changes are consistent with ocean model simulations of warming, in which a decline in biological productivity allows tropical subsurface oxygen to rise even as global ocean oxygen declines. The tropical oxygen increase may have helped avoid a mass extinction during the PETM.

Implications of noncoding regulatory functions in the development of insulinomas.

Insulinomas are rare neuroendocrine tumors arising from pancreatic ß cells, characterized by aberrant proliferation and altered insulin secretion, leading to glucose homeostasis failure. With the aim of uncovering the role of noncoding regulatory regions and their aberrations in the development of these tumors, we coupled epigenetic and transcriptome profiling with whole-genome sequencing. As a result, we unraveled somatic mutations associated with changes in regulatory functions. Critically, these regions impact insulin secretion, tumor development, and epigenetic modifying genes, including polycomb complex components. Chromatin remodeling is apparent in insulinoma-selective domains shared across patients, containing a specific set of regulatory sequences dominated by the SOX17 binding motif. Moreover, many of these regions are H3K27me3 repressed in ß cells, suggesting that tumoral transition involves derepression of polycomb-targeted domains. Our work provides a compendium of aberrant cis-regulatory elements affecting the function and fate of ß cells in their progression to insulinomas and a framework to identify coding and noncoding driver mutations.

Multi-proxy evidence for sea level fall at the onset of the Eocene-Oligocene transition.

Continental-scale expansion of the East Antarctic Ice Sheet during the Eocene-Oligocene Transition (EOT) is one of the largest non-linear events in Earth's climate history. Declining atmospheric carbon dioxide concentrations and orbital variability triggered glacial expansion and strong feedbacks in the climate system. Prominent among these feedbacks was the repartitioning of biogeochemical cycles between the continental shelves and the deep ocean with falling sea level. Here we present multiple proxies from a shallow shelf location that identify a marked regression and an elevated flux of continental-derived organic matter at the earliest stage of the EOT, a time of deep ocean carbonate dissolution and the extinction of oligotrophic phytoplankton groups. We link these observations using an Earth System model, whereby this first regression delivers a pulse of organic carbon to the oceans that could drive the observed patterns of deep ocean dissolution and acts as a transient negative feedback to climate cooling.

Anterior Cruciate Ligament Rehabilitation for the 10- to 18-Year-Old Adolescent Athlete: Practice Guidelines Based on International Delphi Consensus.

Background: There are 2 treatment options for adolescent athletes with anterior cruciate ligament (ACL) injuries-rehabilitation alone (nonsurgical treatment) or ACL reconstruction plus rehabilitation. However, there is no clear consensus on how to include strength and neuromuscular training during each phase of rehabilitation. Purpose: To develop a practical consensus for adolescent ACL rehabilitation to help provide care to this age group using an international Delphi panel. Study Design: Consensus statement. Methods: A 3-round online international Delphi consensus study was conducted. A mix of open and closed literature-based statements were formulated and sent out to an international panel of 20 ACL rehabilitation experts. Statements were divided into 3 domains as follows: (1) nonsurgical rehabilitation; (2) prehabilitation; and (3) postoperative rehabilitation. Consensus was defined as 70% agreement between panel members. Results: Panel members agreed that rehabilitation should consist of 3 criterion-based phases, with continued injury prevention serving as a fourth phase. They also reached a consensus on rehabilitation being different for 10- to 16-year-olds compared with 17- and 18-year-olds, with a need to distinguish between prepubertal (Tanner stage 1) and mid- to postpubertal (Tanner stages 2-5) athletes. The panel members reached a consensus on the following topics: educational topics during rehabilitation; psychological interventions during rehabilitation; additional consultation of the orthopaedic surgeon; duration of postoperative rehabilitation; exercises during phase 1 of nonsurgical and postoperative rehabilitation; criteria for progression from phase 1 to phase 2; resistance training during phase 2; jumping exercises during phase 2; criteria for progression from phase 2 to phase 3; and criteria for return to sports (RTS). The most notable differences in recommendations for prepubertal compared with mid- to postpubertal athletes were described for resistance training and RTS criteria. Conclusion: Together with available evidence, this international Delphi statement provides a framework based on expert consensus and describes a practice guideline for adolescent ACL rehabilitation, which can be used in day-to-day practice. This is an important step toward reducing practice inconsistencies, improving the quality of rehabilitation after adolescent ACL injuries, and closing the evidence-practice gap while waiting for further studies to provide clarity.

Abrupt reversal in ocean overturning during the Palaeocene/Eocene warm period.

An exceptional analogue for the study of the causes and consequences of global warming occurs at the Palaeocene/Eocene Thermal Maximum, 55 million years ago. A rapid rise of global temperatures during this event accompanied turnovers in both marine and terrestrial biota, as well as significant changes in ocean chemistry and circulation. Here we present evidence for an abrupt shift in deep-ocean circulation using carbon isotope records from fourteen sites. These records indicate that deep-ocean circulation patterns changed from Southern Hemisphere overturning to Northern Hemisphere overturning at the start of the Palaeocene/Eocene Thermal Maximum. This shift in the location of deep-water formation persisted for at least 40,000 years, but eventually recovered to original circulation patterns. These results corroborate climate model inferences that a shift in deep-ocean circulation would deliver relatively warmer waters to the deep sea, thus producing further warming. Greenhouse conditions can thus initiate abrupt deep-ocean circulation changes in less than a few thousand years, but may have lasting effects; in this case taking 100,000 years to revert to background conditions.

Evidence for abrupt speciation in a classic case of gradual evolution.

In contrast with speciation in terrestrial organisms, marine plankton frequently display gradual morphological change without lineage division (e.g., phyletic gradualism or gradual evolution), which has raised the possibility that a different mode of evolution dominates within pelagic environments. Here, we reexamine a classic case of putative gradual evolution within the Globorotalia plesiotumida-G. tumida lineage of planktonic foraminifera, and find both compelling evidence for the existence of a third cryptic species during the speciation event and the abrupt evolution of the descendant G. tumida. The third morphotype, not recognized in previous analyses, differs in shape and coiling direction from its ancestor, G. plesiotumida. This species dominates the globorotaliid population for 414,000 years just before the appearance of G. tumida. The first population of the descendant, G. tumida, evolves abruptly within a 44,000-year interval. A combination of morphological data and biostratigraphic evidence suggests that G. tumida evolved by cladogenesis. Our findings provide an unexpected twist on one of the best-documented cases of within-lineage phyletic gradualism and, in doing so, revisit the limitations and promise of the study of speciation in the fossil record.

ICON 2020-International Scientific Tendinopathy Symposium Consensus: A Systematic Review of Outcome Measures Reported in Clinical Trials of Achilles Tendinopathy.

BACKGROUND: Nine core domains for tendinopathy have been identified. For Achilles tendinopathy there is large variation in outcome measures used, and how these fit into the core domains has not been investigated. OBJECTIVE: To identify all available outcome measures outcome measures used to assess the clinical phenotype of Achilles tendinopathy in prospective studies and to map the outcomes measures into predefined health-related core domains. DESIGN: Systematic review. DATA SOURCES: Embase, MEDLINE (Ovid), Web of Science, CINAHL, The Cochrane Library, SPORTDiscus and Google Scholar. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Clinical diagnosis of Achilles tendinopathy, sample size ≥ ten participants, age ≥ 16 years, and the study design was a randomized or non-randomized clinical trial, observational cohort, single-arm intervention, or case series. RESULTS: 9376 studies were initially screened and 307 studies were finally included, totaling 13,248 participants. There were 233 (177 core domain) different outcome measures identified across all domains. For each core domain outcome measures were identified, with a range between 8 and 35 unique outcome measures utilized for each domain. The proportion of studies that included outcomes for predefined core domains ranged from 4% for the psychological factors domain to 72% for the disability domain. CONCLUSION: 233 unique outcome measures for Achilles tendinopathy were identified. Most frequently, outcome measures were used within the disability domain. Outcome measures assessing psychological factors were scarcely used. The next step in developing a core outcome set for Achilles tendinopathy is to engage patients, clinicians and researchers to reach consensus on key outcomes measures. PROSPERO REGISTRATION: CRD42020156763.