Introduction and impact of routine whole genome sequencing in the diagnosis and management of sarcoma.

BACKGROUND: Sarcomas are diverse neoplasms with highly variable histological appearances in which diagnosis is often challenging and management options for metastatic/unresectable disease limited. Many sarcomas have distinctive molecular alterations, but the range of alterations is large, variable in type and rapidly increasing, meaning that testing by limited panels is unable to capture the broad spectrum of clinically pertinent genomic drivers required. Paired whole genome sequencing (WGS) in contrast allows comprehensive assessment of small variants, copy number and structural variants along with mutational signature analysis and germline testing. METHODS: Introduction of WGS as a diagnostic standard for all eligible patients with known or suspected soft tissue sarcoma over a 2-year period at a soft tissue sarcoma treatment centre. RESULTS: WGS resulted in a refinement in the diagnosis in 37% of cases, identification of a target for personalised therapy in 33% of cases, and a germline alteration in 4% of cases. CONCLUSION: Introduction of WGS poses logistical and training challenges, but offers significant benefits to this group of patients.

Large-Area Fabrication of Porous Graphene Networks on Carbon Fabric via Millisecond Photothermal Processing of Polyaniline for Supercapacitors.

Supercapacitors demonstrate promising potential for flexible, multi-functional energy storage devices; however, their widespread adoption is confronted by fabrication challenges. To access a combination of desirable device qualities such as flexibility, lightweight, structural stability, and enhanced electrochemical performance, carbon fiber (CF) can be utilized as a current collector, alongside graphene as an electrochemically active material. Yet achieving a cost-effective, large-scale graphene production, particularly on CF, remains challenging. Here, a rapid (<1 min) photothermal approach is developed for the large-scale production of graphene directly onto CF, utilizing polyaniline (PANI) as a polymer precursor. The in situ electropolymerization of PANI on CF facilitates its rapid synthesis on large areas, followed by conversion into graphene networks, enabling the binder-free fabrication of supercapacitor devices. These devices exhibit an areal capacitance of 180 mF cm-2 (at 2 mA cm-2 in 1 m H2SO4), an order of magnitude higher than other fabric-based devices. Moreover, the devised photothermal strategy allows for one-step preparation of supercapacitor devices on areas exceeding 100 cm-2, yielding an absolute areal capacitance of 4.5 F. The proportional increase in capacitance with device area facilitates scaling and indicates the commercial viability of this approach for low-cost, energy-efficient, and high-throughput production of lightweight, high-performance graphene-based multi-functional supercapacitor devices.

Polyploidy and environmental stress response: a comparative study of fern gametophytes.

Climate change is rapidly altering natural habitats and generating complex patterns of environmental stress. Ferns are major components of many forest understories and, given their independent gametophyte generation, may experience unique pressures in emerging temperature and drought regimes. Polyploidy is widespread in ferns and may provide a selective advantage in these rapidly changing environments. This work aimed to understand whether the gametophytes of allopolyploid ferns respond differently to climate-related physiological stress than their diploid parents. The experimental approach involved a multifactorial design with 27 treatment combinations including exposure to multiple levels of drought and temperature over three treatment durations, with recovery measured at multiple timepoints. We measured Chl fluorescence from over 2000 gametophytes to evaluate stress avoidance and tolerance in diploid and polyploid species. Polyploids generally showed a greater ability to avoid and/or tolerate a range of stress conditions compared with their diploid counterparts, suggesting that polyploidy may confer enhanced flexibility and resilience under climate stress. Overall, these results suggest that polyploidy may provide some resilience to climate change in mixed ploidy populations. However, all species remain susceptible to the impacts of extreme drought and heat stress.

Factors predictive of hospital length of stay in patients with an index episode of acute necrotizing pancreatitis.

INTRODUCTION: Acute necrotizing pancreatitis (ANP) complicates 15 % of acute pancreatitis cases and is associated with prolonged length of stay (LOS). There are limited studies exploring potential predictors. METHODS: We carried out a retrospective study of all consecutive patients presenting to a large referral healthcare system with ANP. Patients younger than 18 years of age, without confirmed glandular necrosis and with in-hospital mortality were excluded. Poisson regression was carried out to identify potential predictors of prolonged hospital stay. RESULTS: One hundred and sixty-two patients hospitalized between December 2016 and June 2020 were included. The median LOS was 12 days (range: 1-155 days). On multivariate analysis, organ dysfunction at presentation (Incidence rate ratio (IRR) 1.21, p = 0.01) or during admission (IRR 1.32, p = 0.001), Charlson Comorbidity Index scores (IRR 1.1 per CCI point, p < 0.001), known chronic pancreatitis (IRR 1.19, p = 0.03), concurrent (non-pancreas related) infections (IRR 1.13, p = 0.04), need for enteral tube placement (IRR 3.42, p < 0.001) and in-hospital interventions (IRR 1.48-2.85 depending on intervention, p < 0.001) were associated with increased LOS. For patients in the cohort to whom this applied, delayed hospital transfers (IRR 1.02, p < 0.001) and delayed start of enteral feeds (IRR 1.01, p = 0.017) contributed to increased overall LOS. CONCLUSION: We demonstrate that multiple factors including delayed transfers to hospitals with pancreaticobiliary expertise lead to increased length of hospitalization. We suggest various strategies that can be considered to target those gaps and may have a favorable effect on LOS.

Recurrent FOSL1 rearrangements in desmoplastic fibroblastoma.

The FOS gene family has been implicated in tumourigenesis across several tumour types, particularly mesenchymal tumours. The rare fibrous tumour desmoplastic fibroblastoma is characterised by overexpression of FOSL1. However, previous studies using cytogenetic and molecular techniques did not identify an underlying somatic change involving the FOSL1 gene to explain this finding. Prompted by an unusual index case, we report the discovery of a novel FOSL1 rearrangement in desmoplastic fibroblastoma using whole-genome and targeted RNA sequencing. We investigated 15 desmoplastic fibroblastomas and 15 fibromas of tendon sheath using immunohistochemistry, in situ hybridisation and targeted RNA sequencing. Rearrangements in FOSL1 and FOS were identified in 10/15 and 2/15 desmoplastic fibroblastomas respectively, which mirrors the pattern of FOS rearrangements observed in benign bone and vascular tumours. Fibroma of tendon sheath, which shares histological features with desmoplastic fibroblastoma, harboured USP6 rearrangements in 9/15 cases and did not demonstrate rearrangements in any of the four FOS genes. The overall concordance between FOSL1 immunohistochemistry and RNA sequencing results was 90%. These findings illustrate that FOSL1 and FOS rearrangements are a recurrent event in desmoplastic fibroblastoma, establishing this finding as a useful diagnostic adjunct and expanding the spectrum of tumours driven by FOS gene family alterations. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

A cutaneous spindle cell neoplasm characterized by a COL3A1::PDGFRA fusion.

Cutaneous spindle cell neoplasms can be challenging to diagnose using routine histopathological techniques alone, and the growing repertoire of molecular studies can assist in diagnosis. We describe a cutaneous spindle cell neoplasm characterized by a COL3A1::PDGFRA rearrangement predicted to lead to constitutive activation of the PDGFRA kinase domain. The lesion shows some similarities to dermatofibrosarcoma protuberans and also benign and epithelioid fibrous histiocytomas but is distinct from these entities histopathologically and molecularly. This tumor is considered to represent an entity in the spectrum of PDGFR-driven cutaneous mesenchymal neoplasms.

Bottlebrush Networks: A Primer for Advanced Architectures.

Bottlebrush networks (BBNs) are an exciting new class of materials with interesting physical properties derived from their unique architecture. While great strides have been made in our fundamental understanding of bottlebrush polymers and networks, an interdisciplinary approach is necessary for the field to accelerate advancements. This review aims to act as a primer to BBN chemistry and physics for both new and current members of the community. In addition to providing an overview of contemporary BBN synthetic methods, we developed a workflow and desktop application (LengthScale), enabling bottlebrush physics to be more approachable. We conclude by addressing several topical issues and asking a series of pointed questions to stimulate conversation within the community.

A reduced role for water transport during the Cenozoic evolution of epiphytic Eupolypod ferns.

The Cretaceous-Cenozoic expansion of tropical forests created canopy space that was subsequently occupied by diverse epiphytic communities including Eupolypod ferns. Eupolypods proliferated in this more stressful niche, where lower competition enabled the adaptive radiation of thousands of species. Here, we examine whether xylem traits helped shape the Cenozoic radiation of Eupolypod ferns. We characterized the petiole xylem anatomy of 39 species belonging to the Eupolypod I and Eupolypod II clades occupying the epiphytic, hemiepiphytic, and terrestrial niche, and we assessed vulnerability to embolism in a subset of species. The transition to the canopy was associated with reduced xylem content and smaller tracheid diameters, but no differences were found in species vulnerability to embolism and pit membrane thickness. Phylogenetic analyses support selection for traits associated with reduced water transport in Eupolypod 1 species. We posit that in Eupolypod epiphytes, selection favored water retention via thicker leaves and lower stomatal density over higher rates of water transport. Consequently, lower leaf water loss was coupled with smaller quantities of xylem and narrower tracheid diameters. Traits associated with water conservation were evident in terrestrial Eupolypod 1 ferns and may have predisposed this clade toward radiation in the canopy.

Utilization pattern of prophylactic measures for prevention of post-ERCP pancreatitis: a National Survey Study.

BACKGROUND AND AIMS: Post-ERCP pancreatitis (PEP) is the most frequent adverse event of ERCP. Various prophylactic measures are endorsed by the American Society for Gastrointestinal Endoscopy and the European Society of Gastrointestinal Endoscopy to both lower the incidence of PEP and to decrease its severity. The extent to which these interventions are practiced throughout the United States is unclear. The aim of this study was to describe the utilization pattern of various PEP measures and determine factors that affect utilization of these measures. METHODS: A 27-question electronic survey was distributed using a cloud-based program (Qualtrics). The questions assessed ERCP training, practice setting, experience, practice patterns, and perceptions for PEP prophylaxis interventions. Endoscopists with practices based in the United States listed in the American Society for Gastrointestinal Endoscopy member directory received a survey invitation via e-mail. The invitation outlined the study and contained a link with instructions to complete the voluntary survey if they had an active ERCP practice. Data were de-identified for the purposes of analysis. RESULTS: Of survey respondents (N = 319), 46% reported therapeutic endoscopy fellowship training and 37% practiced in teaching programs. Annualized ERCP volume of >100 cases per year were reported by 47%, with pancreatic ERCP comprising ≤5% of procedure volume reported by the majority of respondents (61%). The majority of respondents used prophylactic pancreatic stent (PPS), and 54% reported frequent use during high-risk ERCP. The most common indications for PPS were difficult cannulation, to assist biliary access, and multiple pancreatic duct injections. Most respondents reported frequent use of indomethacin (89%). Of physicians who did not use PPS, use of indomethacin was the most common reason (80%). Variables associated with frequent use of PPS were ERCP fellowship training (P ≤ .001), practice at a teaching program (P ≤ .001), <10 years in practice (P = .005), higher procedure volume (P ≤ .001), and higher proportion of pancreatic cases (P ≤ .001). CONCLUSIONS: Physicians with higher annual ERCP volume, who teach at hospital-based ERCP practices, and who regularly perform pancreatic ERCP are more likely to use PPS. Therapeutic ERCP fellowship training and recent entry into practice were also associated with PPS utilization. Indomethacin use seems to be more frequent than PPS. Our findings suggest that indomethacin is supplanting PPS as the preferred method of PEP prophylaxis.

Soft self-expandable metal stent to treat painful pancreatic duct strictures secondary to chronic pancreatitis: a prospective multicenter trial.

BACKGROUND AND AIMS: Fully covered self-expandable metal stents (FCSEMSs) may offer a treatment option for pain associated with a dilated pancreatic duct (PD) in chronic pancreatitis (CP), but optimal patient selection and FCSEMS design, efficacy, and safety remain uncertain. We studied an investigational pancreatic FCSEMS for treatment of CP-associated pain. METHODS: Patients with painful CP, a dominant distal PD stricture, and PD dilation upstream were enrolled in a prospective, multicenter, single-arm trial studying 6-month indwell of a 4- to 6-cm-long soft pancreatic FCSEMS. Primary efficacy and safety endpoints were pain reduction 6 months after FCSEMS indwell (performance goal ≥53%) and PD stenting-related serious adverse events (SAEs), respectively (performance goal <32%). The primary efficacy endpoint was assessed in patients with sufficiently severe and frequent pain at FCSEMS placement as a first stent or in exchange of a plastic stent. RESULTS: Among 67 patients (mean age, 52.7 ± 12.5 years; mean time since CP diagnosis, 6.4 ± 6.4 years), 34 (50.7%) had plastic stent placement within 90 days of FCSEMS placement, and 46 patients were eligible for the primary efficacy endpoint analysis. Technical success was 97.0% (65/67). The observed primary efficacy (26.1%, 12/46) and safety endpoints (31.3%, 21/67) failed to meet the a priori study hypotheses. Study stent migration occurred in 47.7% of patients (31/65). CONCLUSIONS: Six-month treatment with an FCSEMS did not lead to an expected degree of pain reduction, and migrations and SAEs were common. Further study is needed to clarify optimal decompressive strategy, FCSEMS design, and patient selection. (Clinical trial registration number: NCT02802020.).

Adhesion and mechanical properties of poly(dimethylsiloxane) bottlebrush elastomers.

Poly(dimethylsiloxane) (PDMS) bottlebrush elastomers (BBEs) are attractive soft materials with well-controlled bulk mechanical properties. However, their surface and interfacial properties have not been studied in depth. We report a detailed study of the adhesion of PDMS BBEs to glass using a contact adhesion test to determine the critical energy release rates, Gc, as a function of interfacial separation velocity. For BBEs, Gc for initiating separation, G0, was found to be independent of the crosslink density. We hypothesize that the monomer chemistry of side chains plays a primary role in defining surface properties for this materials system. After crack initiation, BBEs showed a significantly lower Gc and less velocity dependence than linear chain networks. Scaling analysis attributes these properties to the faster dissipative relaxation mechanisms within the BBEs. These findings demonstrate that the adhesion properties of BBEs can be finely tuned through the monomer chemistry and side chain length for potential applications.

Functional traits and trait coordination change over the life of a leaf in a tropical fern species.

PREMISE: Plant ecological strategies are often defined by the integration of underlying traits related to resource acquisition, allocation, and growth. Correlations between key traits across diverse plants suggest that variation in plant ecological strategies is largely driven by a fast-slow continuum of plant economics. However, trait correlations may not be constant through the life of a leaf, and it is still poorly understood how trait function varies over time in long-lived leaves. METHODS: Here, we compared trait correlations related to resource acquisition and allocation across three different mature frond age cohorts in a tropical fern species, Saccoloma inaequale. RESULTS: Fronds exhibited high initial investments of nitrogen and carbon, but with declining return in photosynthetic capacity after the first year. In the youngest fronds, we found water-use efficiency to be significantly lower than in the oldest mature fronds due to increased transpiration rates. Our data suggest that middle-aged fronds are more efficient relative to younger, less water-use efficient fronds and that older fronds exhibit greater nitrogen investments without higher photosynthetic return. In addition, several trait correlations expected under the leaf economics spectrum (LES) do not hold within this species, and some trait correlations only appear in fronds of a specific developmental age. CONCLUSIONS: These findings contextualize the relationship between traits and leaf developmental age with those predicted to underlie plant ecological strategy and the LES and are among the first pieces of evidence for when relative physiological trait efficiency is maximized in a tropical fern species.

Timing of ERCP after extracorporeal shock wave lithotripsy for large main pancreatic duct stones.

BACKGROUND AND AIMS: Extracorporeal shock wave lithotripsy (ESWL) is performed to fragment large main pancreatic duct (MPD) stones in symptomatic patients. Subsequent endoscopic retrograde cholangiopancreatography (ERCP) is often performed to clear the stone fragments. Edema of surrounding tissue after ESWL theoretically affects the ability to perform ERCP. However, the optimal timing of ERCP after ESWL is not clearly defined. The aim of this study is to determine the efficacy and safety of same-day ERCP after ESWL and to determine if the timing of ERCP after ESWL affects outcomes. METHODS: This is a retrospective study of consecutive patients from January, 2013 to September, 2019 who received ESWL for MPD stones at our center. Included patients received subsequent same-day ERCP under the same general anesthesia session or later session ERCP (1-30 days after ESWL). Demographics, anatomical findings, history, and outcomes were collected. Success was defined as complete or near complete (> 80%) stone fragmentation with clearance. RESULTS: 218 patients were treated with ESWL and subsequent ERCP. 133 (61.0%) received ERCP on the same day immediately after ESWL, while 85 (39.0%) returned for ERCP at a later day (median 3.0 days after ESWL). Baseline characteristics demonstrated patients who received same-day ERCP had a higher rate of pain at baseline (94.7% vs 87.1%, p = 0.045). Main outcomes demonstrated an overall successful MPD stone clearance rate of 90.4%, with similar rates between same-day ERCP and later session ERCP (91.7% vs 88.2%, p = 0.394). Additionally, successful cannulation at ERCP, adverse events, and post-procedure admission rates were similar. CONCLUSIONS: Delaying ERCP to allow peripancreatic tissue recovery after ESWL does not affect outcomes. Same-day ERCP after ESWL is safe and effective.

Silicone elastomers and the Persson-Brener adhesion model.

Many modern anti-icing and anti-fouling coatings rely on soft, low surface energy elastomeric materials such as polydimethylsiloxane for their functionality. While the low surface energy is desirable for reducing adhesion, very little work considers the larger contribution to adhesive failure caused by the viscoelastic nature of elastomers. Here we examine several different siloxane elastomers using a JKR adhesion test, which was operated over a range of different speeds and temperatures. Additionally, we characterize the dynamic mechanical modulus over a large range of frequencies for each material. We note that surface energies of the materials are all similar, but variation in adhesion strength is clear in the data. The variation at low speeds is related to elastomer architecture but the speed dependence itself is independent of architecture. Qualitative correlations are noted between the JKR adhesion measurements and the dynamic moduli. Finally, an attempt is made to directly compare moduli and adhesion through the recent Persson-Brener model. Approximations of the model are shown to be inaccurate. The full model is found to be accurate at low speeds, although it fails to precisely capture higher speed behaviour.

The NHS England 100,000 Genomes Project: feasibility and utility of centralised genome sequencing for children with cancer.

BACKGROUND: Whole-genome sequencing (WGS) of cancers is becoming an accepted component of oncological care, and NHS England is currently rolling out WGS for all children with cancer. This approach was piloted during the 100,000 genomes (100 K) project. Here we share the experience of the East of England Genomic Medicine Centre (East-GMC), reporting the feasibility and clinical utility of centralised WGS for individual children locally. METHODS: Non-consecutive children with solid tumours were recruited into the pilot 100 K project at our Genomic Medicine Centre. Variant catalogues were returned for local scrutiny and appraisal at dedicated genomic tumour advisory boards with an emphasis on a detailed exploration of potential clinical value. RESULTS: Thirty-six children, representing one-sixth of the national 100 K cohort, were recruited through our Genomic Medicine Centre. The diagnoses encompassed 23 different solid tumour types and WGS provided clinical utility, beyond standard-of-care assays, by refining (2/36) or changing (4/36) diagnoses, providing prognostic information (8/36), defining pathogenic germline mutations (1/36) or revealing novel therapeutic opportunities (8/36). CONCLUSION: Our findings demonstrate the feasibility and clinical value of centralised WGS for children with cancer. WGS offered additional clinical value, especially in diagnostic terms. However, our experience highlights the need for local expertise in scrutinising and clinically interpreting centrally derived variant calls for individual children.

Microbiology of bile aspirates obtained at ERCP in patients with suspected acute cholangitis.

BACKGROUND: The cornerstone of treatment for acute cholangitis is source control with biliary drainage and early antibiotics. The primary aim of this study was to describe the microbiology of bile aspirate pathogens obtained at the time of endoscopic retrograde cholangiopancreatography (ERCP) in patients suspected of having acute cholangitis. METHODS: In this single-center retrospective study, patients were included if a bile aspirate was collected at ERCP for suspicion of acute cholangitis, from 1 January 2010 to 31 December 2016. RESULTS: There were 721 ERCP procedures for suspected acute cholangitis with bile culture results, with 662 positive bile cultures (91.8 %). Pathogens included: Enterococcus species (spp.) 448 (67.7 %); Klebsiella spp. 295 (44.6 %); Escherichia coli 269 (40.6 %); Pseudomonas spp. 52 (7.9 %); and anaerobes 64 (9.7 %). Susceptibility of Klebsiella pneumoniae and E.coli isolates to ciprofloxacin was 88 % and 64 %, respectively. Extended-spectrum beta-lactamases and carbapenem resistance were found in 7.9 % and 3.6 % of Enterobacteriaceae, respectively. There were 437 concurrent blood cultures, of which 174 were positive (39.8 % of cultures drawn). Prior biliary endoscopic sphincterotomy (ES) was evident in 459 ERCP cases (63.7 %), and was associated with increased frequency of Klebsiella spp., Pseudomonas aeruginosa, Enterobacter spp., and Enterococcus spp. Prior biliary ES significantly increased the probability of vancomycin-resistant Enterococcus (VRE). CONCLUSIONS: The vast majority of bile cultures (91.8 %) were positive. The susceptibilities of E.coli and K.pneumoniae to ciprofloxacin are lower than historically noted. A notable portion of cultures contained pathogenic drug-resistant organisms. Prior biliary ES is associated with a higher frequency of certain organisms and higher frequency of VRE.

Antheridiogen controls spatial dynamics of sex expression in naturally occurring gametophytes of the tree fern Cyathea multiflora.

PREMISE: Antheridiogen systems are a set of pheromonal mechanisms that control sex expression in fern gametophytes. However, antheridiogen has rarely been studied outside of the laboratory, and little is known about its function in natural settings. Combining predictions based on field and laboratory study, we tested whether the sexual structure of gametophytic colonies of a tree fern were attributable to antheridiogen. METHODS: Gametophytic colonies of the antheridiogen-producing tree fern Cyathea multiflora were collected at La Selva Biological Station in Costa Rica in January 2019. The sex of each gametophyte was determined, mapped, and spatial statistic approaches were used to examine the distribution of sex in each colony. RESULTS: In all gametophytic colonies, males were most common, representing 62-68% of individuals. No hermaphroditic gametophytes were identified in any colony. A quadrat-based method showed female gametophytes were not clustered in each colony, while male gametophytes were clustered. In two of the colonies, the K(r) test statistic for males was greater than expected compared to random simulations of sex expression, indicating male sex expression was spatially associated with females. CONCLUSIONS: This study provides the first documentation of spatial sex expression in natural settings of gametophytes of an antheridiogen-producing tree fern species. The profound impact of antheridiogen on gametophytic sex expression in field settings suggests this system is intimately tied to mating system, fitness, and genetic diversity in Cyathea multiflora.

Clear cell variant of atypical fibroxanthoma and pleomorphic dermal sarcoma: Molecular characterization and review of the literature.

Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are unusual cutaneous tumors that typically arise in sun-damaged skin of elderly individuals. Several histopathologic variants have been described, but the clear cell variant is particularly rare with only 18 cases of AFX and one case of PDS reported. Here, we present two cases of clear cell AFX and PDS highlighting key histopathologic findings and molecular alterations assessed by next-generation sequencing.

A comparative study between single-operator pancreatoscopy with intraductal lithotripsy and extracorporeal shock wave lithotripsy for the management of large main pancreatic duct stones.

BACKGROUND AND AIMS: Endoscopic management of large main pancreatic ductal (MPD) stones often require treatment with lithotripsy. Extracorporeal shock wave lithotripsy (ESWL) has been the mainstay therapy, and single-operator pancreatoscopy with intraductal (intracorporeal) lithotripsy (SOPIL) is an emerging technique. However, no comparative studies between these techniques exist. We therefore aimed to compare ESWL to SOPIL for the treatment of large MPD stones. METHODS: This is a retrospective cohort study comparing patients who were treated with ESWL or SOPIL from September 2013 to September 2019 at a single tertiary center. Logistic regression was performed to identify factors associated with technical success and efficient stone clearance (≤ 2 procedures to clear stones). RESULTS: There were 240 patients who were treated with ESWL and 18 treated with SOPIL. The overall technical success rate of stone clearance was 224/258 (86.8%), which was similar between the ESWL and SOPIL groups (86.7% vs 88.9%, p = 1.000). A SOPIL approach required fewer total procedures (1.6 ± 0.6 vs 3.1 ± 1.5, p < 0.001) and less aggregate procedure time (101.6 ± 68.2 vs 191.8 ± 111.6 min, p = 0.001). Adverse event rates were similar between the groups (6.3% vs 5.6%, p = 1.000). The use of SOPIL was independently associated with greater efficiency compared to ESWL (OR 5.241 [1.348-20.369], p = 0.017). Stone size > 10 mm was associated with less efficient stone clearance (OR 0.484 [0.256-0.912], p = 0.025). CONCLUSION: Both ESWL and SOPIL are safe and effective endoscopic adjunct modalities for treating large pancreatic duct stones. SOPIL is an emerging alternative to ESWL that is potentially more efficient for lithotripsy and MPD stone clearance.

Ca isotopes record rapid crystal growth in volcanic and subvolcanic systems.

Kinetic calcium isotope effects can be used as growth-rate proxies for volcanic and subvolcanic minerals. Here, we analyze Ca isotopic compositions in experimental and natural samples and confirm that large kinetic effects (>2‰) can occur during magmatic plagioclase crystallization. Experiments confirm theoretical predictions that disequilibrium isotope effects depend mainly on the rates for crystal growth relative to liquid phase Ca diffusivity (R/D). Plagioclase phenocrysts from the 1915 Mount Lassen rhyodacite eruption, the ∼650-y-old Deadman Creek Dome eruption, and several mafic subvolcanic orbicules and plagioclase comb layers from Northern California have disequilibrium Ca isotopic compositions that suggest rapid crystal growth rates (>1 cm/y to 15 cm/y). The Ca isotope results, combined with complementary crystal-size distribution analyses, suggest that magmatic rejuvenation (and eruption) events, as reflected in crystal growth times, can be as short as ∼10-3 y. Although mafic systems are predicted to have shorter magmatic rejuvenation periods, we find similarly short timescales in both mafic and silicic systems. These results are consistent with a growing body of evidence suggesting that dominantly crystalline volcanic magma reservoirs can be rapidly reactivated by the injection of fresh magma prior to eruption. By focusing on a common mineral such as plagioclase, this approach can be applied across all major magmatic compositions, suggesting that Ca isotopes can be used as a tool for investigating the dynamics and timing of volcanic eruptions.