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.

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.

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).

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.

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.

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.

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.

Correction: A Neolithic Mega-Tsunami Event in the Eastern Mediterranean: Prehistoric Settlement Vulnerability Along the Carmel Coast, Israel.

[This corrects the article DOI: 10.1371/journal.pone.0243619.].

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.

Paleo-diatom composition from Santa Barbara Basin deep-sea sediments: a comparison of 18S-V9 and diat-rbcL metabarcoding vs shotgun metagenomics.

Sedimentary ancient DNA (sedaDNA) analyses are increasingly used to reconstruct marine ecosystems. The majority of marine sedaDNA studies use a metabarcoding approach (extraction and analysis of specific DNA fragments of a defined length), targeting short taxonomic marker genes. Promising examples are 18S-V9 rRNA (~121-130 base pairs, bp) and diat-rbcL (76 bp), targeting eukaryotes and diatoms, respectively. However, it remains unknown how 18S-V9 and diat-rbcL derived compositional profiles compare to metagenomic shotgun data, the preferred method for ancient DNA analyses as amplification biases are minimised. We extracted DNA from five Santa Barbara Basin sediment samples (up to ~11 000 years old) and applied both a metabarcoding (18S-V9 rRNA, diat-rbcL) and a metagenomic shotgun approach to (i) compare eukaryote, especially diatom, composition, and (ii) assess sequence length and database related biases. Eukaryote composition differed considerably between shotgun and metabarcoding data, which was related to differences in read lengths (~112 and ~161 bp, respectively), and overamplification of short reads in metabarcoding data. Diatom composition was influenced by reference bias that was exacerbated in metabarcoding data and characterised by increased representation of Chaetoceros, Thalassiosira and Pseudo-nitzschia. Our results are relevant to sedaDNA studies aiming to accurately characterise paleo-ecosystems from either metabarcoding or metagenomic data.

A Neolithic mega-tsunami event in the eastern Mediterranean: Prehistoric settlement vulnerability along the Carmel coast, Israel.

Tsunami events in antiquity had a profound influence on coastal societies. Six thousand years of historical records and geological data show that tsunamis are a common phenomenon affecting the eastern Mediterranean coastline. However, the possible impact of older tsunamis on prehistoric societies has not been investigated. Here we report, based on optically stimulated luminescence chronology, the earliest documented Holocene tsunami event, between 9.91 to 9.29 ka (kilo-annum), from the eastern Mediterranean at Dor, Israel. Tsunami debris from the early Neolithic is composed of marine sand embedded within fresh-brackish wetland deposits. Global and local sea-level curves for the period, 9.91-9.29 ka, as well as surface elevation reconstructions, show that the tsunami had a run-up of at least ~16 m and traveled between 3.5 to 1.5 km inland from the palaeo-coastline. Submerged slump scars on the continental slope, 16 km west of Dor, point to the nearby "Dor-complex" as a likely cause. The near absence of Pre-Pottery Neolithic A-B archaeological sites (11.70-9.80 cal. ka) suggest these sites were removed by the tsunami, whereas younger, late Pre-Pottery Neolithic B-C (9.25-8.35 cal. ka) and later Pottery-Neolithic sites (8.25-7.80 cal. ka) indicate resettlement following the event. The large run-up of this event highlights the disruptive impact of tsunamis on past societies along the Levantine coast.

On impact and volcanism across the Cretaceous-Paleogene boundary.

The cause of the end-Cretaceous mass extinction is vigorously debated, owing to the occurrence of a very large bolide impact and flood basalt volcanism near the boundary. Disentangling their relative importance is complicated by uncertainty regarding kill mechanisms and the relative timing of volcanogenic outgassing, impact, and extinction. We used carbon cycle modeling and paleotemperature records to constrain the timing of volcanogenic outgassing. We found support for major outgassing beginning and ending distinctly before the impact, with only the impact coinciding with mass extinction and biologically amplified carbon cycle change. Our models show that these extinction-related carbon cycle changes would have allowed the ocean to absorb massive amounts of carbon dioxide, thus limiting the global warming otherwise expected from postextinction volcanism.

The impact of proinflammatory cytokines on the ß-cell regulatory landscape provides insights into the genetics of type 1 diabetes.

The early stages of type 1 diabetes (T1D) are characterized by local autoimmune inflammation and progressive loss of insulin-producing pancreatic ß cells. Here we show that exposure to proinflammatory cytokines reveals a marked plasticity of the ß-cell regulatory landscape. We expand the repertoire of human islet regulatory elements by mapping stimulus-responsive enhancers linked to changes in the ß-cell transcriptome, proteome and three-dimensional chromatin structure. Our data indicate that the ß-cell response to cytokines is mediated by the induction of new regulatory regions as well as the activation of primed regulatory elements prebound by islet-specific transcription factors. We find that T1D-associated loci are enriched with newly mapped cis-regulatory regions and identify T1D-associated variants disrupting cytokine-responsive enhancer activity in human ß cells. Our study illustrates how ß cells respond to a proinflammatory environment and implicate a role for stimulus response islet enhancers in T1D.

The Effect of Formalin Fixation on Resection Margins in Colorectal Cancer.

Resection margins in colorectal cancer carry clinical significance with regard to disease recurrence risk and selection for multimodal adjuvant therapy, especially with circumferential resection margins in rectal cancer. Colorectal cancer specimens are routinely fixed in formalin, which results in specimen and tumor-free margin shrinkage. However, the effects of shrinkage have not traditionally been taken into account when analyzing tumor-free margins. In this prospective study, 46 colorectal cancer specimens were measured in the fresh state and subsequently after formalin fixation for total specimen length, distal resection margin, and radial margin (circumferential resection margin for rectal cancer). The mean reduction after formalin fixation was 17.48 mm (14.7%) for distal resection margin and 1.20 mm (10.5%) for radial margin. For rectal cancer, circumferential resection margin reduction was 0.88 mm (11.8%); this was not affected by neoadjuvant chemoradiotherapy. Duration of formalin fixation did not significantly affect the extent of margin shrinkage. This is the first study to evaluate the effect of formalin fixation on radial resection margins, specifically as it relates to rectal cancer, and it demonstrates that shrinkage from formalin fixation should be a consideration in decision-making where the magnitude of tumor-free margins is small.

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.

Diagnostic challenges in a patient with an occult insulinoma:68 Ga-DOTA-exendin-4 PET/CT and 68Ga-DOTATATE PET/CT.

Despite growing evidence for GLP-1R molecular-based imaging, successful localization of insulinomas may require the use of multiple imaging modalities. Not all benign insulinomas express the GLP-1R as expected. Our case demonstrates that there is a still an important role for traditional methods for the anatomical localization of an insulinoma.

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.

Prehistorical and historical declines in Caribbean coral reef accretion rates driven by loss of parrotfish.

Caribbean coral reefs have transformed into algal-dominated habitats over recent decades, but the mechanisms of change are unresolved due to a lack of quantitative ecological data before large-scale human impacts. To understand the role of reduced herbivory in recent coral declines, we produce a high-resolution 3,000 year record of reef accretion rate and herbivore (parrotfish and urchin) abundance from the analysis of sediments and fish, coral and urchin subfossils within cores from Caribbean Panama. At each site, declines in accretion rates and parrotfish abundance were initiated in the prehistorical or historical period. Statistical tests of direct cause and effect relationships using convergent cross mapping reveal that accretion rates are driven by parrotfish abundance (but not vice versa) but are not affected by total urchin abundance. These results confirm the critical role of parrotfish in maintaining coral-dominated reef habitat and the urgent need for restoration of parrotfish populations to enable reef persistence.