Glypican 4 and Mmp14 interact in regulating the migration of anterior endodermal cells by limiting extracellular matrix deposition.

During embryogenesis, the germ layers, including the endoderm, undergo convergence and extension movements to narrow and elongate the body plan. In zebrafish, the dorsal migration of endodermal cells during gastrulation is controlled by chemokine signaling, but little is known about how they migrate during segmentation. Here, we show that glypican 4 (Gpc4), a member of the heparin sulfate proteoglycan family, is required for efficient migration of anterior endodermal cells during early segmentation, regulating Rac activation to maintain polarized actin-rich lamellipodia. An endoderm transplantation assay showed that Gpc4 regulates endoderm migration in a non-cell-autonomous fashion. Further analyses revealed that the impaired endoderm migration in gpc4 mutants results from increases in the expression and assembly of fibronectin and laminin, major components of the extracellular matrix (ECM). Notably, we found that matrix metalloproteinase 14 (Mmp14a/b) is required for the control of ECM expression during endoderm migration, with Gpc4 acting through Mmp14a/b to limit ECM expression. Our results suggest that Gpc4 is crucial for generating the environment required for efficient migration of endodermal cells, uncovering a novel function of Gpc4 during development.

Implementation of an injury prevention programme in community netball: An observational study.

The Netball KNEE programme is a freely available, netball-specific injury prevention programme promoted to netball coaches. However, little is known about its implementation. This cross-sectional study aimed to evaluate the implementation of the Netball KNEE programme in community netball, and determine if implementation differed by player age. Four netball clubs participated. Training sessions (n = 67) were observed to determine if coaches used Netball KNEE programme activities as intended, modified or not at all during training, and whether feedback on technique was provided. No team performed the recommended number of activities without modification. On average, only 12%, 18% and 14% of the recommended number of activities were performed as intended in the 7-10, 11-13 and ≥14 years age groups, respectively. Warm-up/footwork activities (30%; 0-80%) were more frequently performed than strength (0%; 0-50%), balance/landing (0%; 0-50%), and agility (0%; 0-25%) activities (p < 0.001). Feedback was required in 65% of activities, but frequently not provided (56%). Netball KNEE programme implementation is low in community netball, particularly strength, balance/landing and agility activities. This finding, and lack of provision of feedback on technique, is concerning as improving movement patterns is a key aim of injury prevention programmes.

The relationship between adverse interpersonal experiences and self-esteem in people with intellectual disabilities: The role of shame, self-compassion and social support.

BACKGROUND: People with intellectual disabilities are reported to have low self-esteem and to experience high rates of adverse interpersonal experiences (AIEs). This study aimed to investigate whether shame and self-compassion mediate the relationship between AIEs and self-esteem for people with intellectual disabilities and whether perceived social support moderates this relationship. METHOD: This study employed a cross-sectional design, involving between-group comparisons. Forty-seven people with intellectual disabilities and 50 people without intellectual disabilities completed self-report questionnaires measuring shame, self-compassion, self-esteem, early AIEs and social support. RESULTS: Shame and self-compassion were found to mediate the relationship between AIEs and self-esteem for people with intellectual disabilities. There was no evidence for a moderating effect of social support and no difference between groups in shame or self-compassion. CONCLUSIONS: The findings suggest shame and self-compassion are important concepts for people with intellectual disabilities. Clinical and research implications are discussed.

Establishing a Smartphone Ambulatory ECG Service for Patients Presenting to the Emergency Department with Pre-Syncope and Palpitations.

Background and Objectives: The Investigation of Palpitations in the ED (IPED) study showed that a smartphone-based event recorder increased the number of patients in whom an electrocardiogram (ECG) was captured during symptoms over five-fold to more than 55% at 90 days compared to standard care and concluded that this safe, non-invasive and easy-to-use device should be considered part of on-going care to all patients presenting acutely with unexplained palpitations or pre-syncope. This study reports the process of establishing a smartphone palpitation and pre-syncope ambulatory care Clinic (SPACC) service. Materials and Methods: A clinical standard operating procedure (SOP) was devised, and funding was secured through a business case for the purchase of 40 AliveCor devices in the first instance. The clinic was launched on 22 July 2019. Results: Between 22 July 2019 and 31 October 2019, 68 patients seen in the emergency departments (EDs) with palpitations or pre-syncope were referred to SPACC. Of those, 30 were male and 38 were female, and the mean age was 45.8 years old (SD 15.1) with a range from 18 years old to 80 years old. A total of 50 (74%) patients underwent full investigation. On the first assessment, seven (10%) patients were deemed to have non-cardiac palpitations and were not fitted with the device. All patients who underwent full investigation achieved symptomatic rhythm correlation most with sinus rhythm, ventricular ectopics, or bigeminy. A symptomatic cardiac dysrhythmia was detected in six (8.8%) patients. Three patients had supraventricular tachycardia (4%), two had atrial fibrillation (3%), and one had atrial flutter (2%). Qualitative feedback from the SPACC team suggested several areas where improvement to the clinic could be made. Conclusion: We believe a smartphone palpitation service based on ambulatory care is simple to implement and is effective at detecting cardiac dysrhythmia in ED palpitation patients.

Anatomical Evaluation of a Conventional Pectoralis II Versus a Subserratus Plane Block for Breast Surgery.

BACKGROUND: Pectoralis I and II (Pecs I/Pecs II) blocks are modern regional anesthetic techniques performed in combination to anesthetize the nerves involved in breast surgery and axillary node dissection. Pecs II spread and clinical efficacy is thought to be independent of whether injection occurs between pectoralis minor and serratus anterior or deep to serratus anterior. Injecting deep to serratus anterior onto the rib may be technically easier; however, our clinical experience suggests that this approach may be less effective for axillary dissection. We undertook a cadaveric study to evaluate a subserratus plane approach for use in breast and axillary surgery. METHODS: Ultrasound-guided blocks using methylene blue dye were performed on 4 Genelyn-embalmed cadavers to assess and compare dye spread after a conventional Pecs II and a subserratus plane block at the third rib. RESULTS: Conventional Pecs II injection demonstrated staining of the intercostobrachial nerve, third intercostal nerve, thoracodorsal nerve, long thoracic nerve, medial pectoral, and lateral pectoral nerve. The subserratus plane produced significantly less axillary spread, incomplete staining of the medial pectoral, and very minimal staining of the lateral pectoral nerve. Dye spread was limited to the lateral cutaneous branches of the intercostal nerves in both injections. CONCLUSIONS: In our cadaveric study, injecting deep to serratus plane produced significantly less axillary spread. For breast surgery excluding the axilla, both techniques may be effective; however, for axillary dissection, the conventional Pecs II is likely to produce superior analgesia and additionally may help achieve complete coverage of the deeper pectoral nerve branches.

Timing and causes of mid-Holocene mammoth extinction on St. Paul Island, Alaska.

Relict woolly mammoth (Mammuthus primigenius) populations survived on several small Beringian islands for thousands of years after mainland populations went extinct. Here we present multiproxy paleoenvironmental records to investigate the timing, causes, and consequences of mammoth disappearance from St. Paul Island, Alaska. Five independent indicators of extinction show that mammoths survived on St. Paul until 5,600 ± 100 y ago. Vegetation composition remained stable during the extinction window, and there is no evidence of human presence on the island before 1787 CE, suggesting that these factors were not extinction drivers. Instead, the extinction coincided with declining freshwater resources and drier climates between 7,850 and 5,600 y ago, as inferred from sedimentary magnetic susceptibility, oxygen isotopes, and diatom and cladoceran assemblages in a sediment core from a freshwater lake on the island, and stable nitrogen isotopes from mammoth remains. Contrary to other extinction models for the St. Paul mammoth population, this evidence indicates that this mammoth population died out because of the synergistic effects of shrinking island area and freshwater scarcity caused by rising sea levels and regional climate change. Degradation of water quality by intensified mammoth activity around the lake likely exacerbated the situation. The St. Paul mammoth demise is now one of the best-dated prehistoric extinctions, highlighting freshwater limitation as an overlooked extinction driver and underscoring the vulnerability of small island populations to environmental change, even in the absence of human influence.

Testate amoeba records indicate regional 20th-century lowering of water tables in ombrotrophic peatlands in central-northern Alberta, Canada.

Testate amoebae are abundant in the surface layers of northern peatlands. Analysis of their fossilized shell (test) assemblages allows for reconstructions of local water-table depths (WTD). We have reconstructed WTD dynamics for five peat cores from peatlands ranging in distance from the Athabasca bituminous sands (ABS) region in western Canada. Amoeba assemblages were combined with plant macrofossil records, acid-insoluble ash (AIA) fluxes and instrumental climate data to identify drivers for environmental change. Two functional traits of testate amoebae, mixotrophy and the tendency to integrate xenogenic mineral matter in test construction, were quantified to infer possible effects of AIA flux on testate amoeba presence. Age-depth models showed the cores each covered at least the last ~315 years, with some spanning the last millennium. Testate amoeba assemblages were likely affected by permafrost development in two of the peatlands, yet the most important shift in assemblages was detected after 1960 CE. This shift represents a significant apparent lowering of water tables in four out of five cores, with a mean drop of ~15 cm. Over the last 50 years, assemblages shifted towards more xerophilous taxa, a trend which was best explained by increasing Sphagnum s. Acutifolia and, to a lesser extent, mean summer temperature. This trend was most evident in the two cores from the sites located farthest away from the ABS region. AIA flux variations did not show a clear effect on mineral-agglutinating taxa, nor on S. s. Acutifolia presence. We therefore suggest the drying trend was forced by the establishment of S. s. Acutifolia, driven by enhanced productivity following regional warming. Such recent apparent drying of peatlands, which may only be reconstructed by appropriate indicators combined with high chronological control, may affect vulnerability to future burning and promote emissions of CO2 .

Peat Bogs Document Decades of Declining Atmospheric Contamination by Trace Metals in the Athabasca Bituminous Sands Region.

Peat cores were collected from five bogs in the vicinity of open pit mines and upgraders of the Athabasca Bituminous Sands, the largest reservoir of bitumen in the world. Frozen cores were sectioned into 1 cm slices, and trace metals determined in the ultraclean SWAMP lab using ICP-QMS. The uppermost sections of the cores were age-dated with 210Pb using ultralow background gamma spectrometry, and selected plant macrofossils dated using 14C. At each site, trace metal concentrations as well as enrichment factors (calculated relative to the corresponding element/Th ratio of the Upper Continental Crust) reveal maximum values 10 to 40 cm below the surface which shows that the zenith of atmospheric contamination occurred in the past. The age-depth relationships show that atmospheric contamination by trace metals (Ag, Cd, Sb, Tl, but also V, Ni, and Mo which are enriched in bitumen) has been declining in northern Alberta for decades. In fact, the greatest contemporary enrichments of Ag, Cd, Sb, and Tl (in the top layers of the peat cores) are found at the control site (Utikuma) which is 264 km SW, suggesting that long-range atmospheric transport from other sources must be duly considered in any source assessment.

Airborne Petcoke Dust is a Major Source of Polycyclic Aromatic Hydrocarbons in the Athabasca Oil Sands Region.

Oil sands mining has been linked to increasing atmospheric deposition of polycyclic aromatic hydrocarbons (PAHs) in the Athabasca oil sands region (AOSR), but known sources cannot explain the quantity of PAHs in environmental samples. PAHs were measured in living Sphagnum moss (24 sites, n = 68), in sectioned peat cores (4 sites, n = 161), and snow (7 sites, n = 19) from ombrotrophic bogs in the AOSR. Prospective source samples were also analyzed, including petroleum coke (petcoke, from both delayed and fluid coking), fine tailings, oil sands ore, and naturally exposed bitumen. Average PAH concentrations in near-field moss (199 ng/g, n = 11) were significantly higher (p = 0.035) than in far-field moss (118 ng/g, n = 13), and increasing temporal trends were detected in three peat cores collected closest to industrial activity. A chemical mass-balance model estimated that delayed petcoke was the major source of PAHs to living moss, and among three peat core the contribution to PAHs from delayed petcoke increased over time, accounting for 45-95% of PAHs in contemporary layers. Petcoke was also estimated to be a major source of vanadium, nickel, and molybdenum. Scanning electron microscopy with energy-dispersive X-ray spectroscopy confirmed large petcoke particles (>10 µm) in snow at near-field sites. Petcoke dust has not previously been considered in environmental impact assessments of oil sands upgrading, and improved dust control from growing stockpiles may mitigate future risks.

Experiences from an interprofessional student-assisted chronic disease clinic.

Faced with significant health and workforce challenges in the region, the Central Queensland Health Service District (CQHSD) commenced a student-assisted clinical service. The Capricornia Allied Health Partnership (CAHP) is an interprofessional clinical placement program in which pre-entry students from exercise physiology, nutrition and dietetics, occupational therapy, pharmacy, podiatry and social work are embedded in a collaborative chronic disease service delivery model. The model coordinates multiple student clinical placements to: address service delivery gaps for previously underserved people with chronic disease in need of early intervention and management; provide an attractive clinical placement opportunity for students that will potentially lead to future recruitment success, and demonstrate leadership in developing future health workforce trainees to attain appropriate levels of interprofessional capacity. The CAHP clinic commenced student placements and client services in February 2010. This report provides early evaluative information regarding student experiences included self-reported changes in practice.

Capricornia Allied Health Partnership (CAHP): a case study of an innovative model of care addressing chronic disease through a regional student-assisted clinic.

Faced with significant health and workforce challenges, the Central Queensland Hospital and Health Service commenced an innovative student-assisted clinical model of care. The Capricornia Allied Health Partnership (CAHP) in 2010. The clinic supports pre-entry allied health student clinical placements to: (1) address service delivery gaps for previously underserved people with chronic disease; (2) facilitate hospital avoidance and early discharge from the local hospital; (3) provide an attractive clinical placement opportunity for allied health students that will potentially lead to future recruitment success, and (4) demonstrate leadership in developing interprofessional skills of future health workforce trainees. This case study details the conceptual background of the initial model, the key features of the clinical placement and service delivery model, and discusses the current and future evaluation of the clinic.

Optimising Patient Outcomes in Tongue Cancer: A Multidisciplinary Approach.

A multidisciplinary approach to the management of tongue cancer is vital for achieving optimal patient outcomes. Nursing and allied health professionals play essential roles within the team. We developed symposia comprising a series of online lectures offering a detailed perspective on the role each discipline and consumer perspective has in the management of patients with tongue cancer. The topics, including epidemiology and prevention, diagnosis, treatment planning, surgery, adjuvant care, and the management of recurrent or metastatic disease, were thoroughly examined. The symposia highlighted the significance of fostering collaboration and continuous learning through a multidisciplinary approach. This initiative should be relevant to healthcare professionals, researchers, and policymakers striving to enhance patient outcomes in tongue cancer care through innovative collaboration.

BMP4 sufficiency to induce choroid plexus epithelial fate from embryonic stem cell-derived neuroepithelial progenitors.

Choroid plexus epithelial cells (CPECs) have essential developmental and homeostatic roles related to the CSF and blood-CSF barrier they produce. Accordingly, CPEC dysfunction has been implicated in many neurological disorders, such as Alzheimer's disease, and transplant studies have provided proof-of-concept for CPEC-based therapies. However, such therapies have been hindered by the inability to expand or generate CPECs in culture. During development, CPECs differentiate from preneurogenic neuroepithelial cells and require bone morphogenetic protein (BMP) signaling, but whether BMPs suffice for CPEC induction is unknown. Here we provide evidence for BMP4 sufficiency to induce CPEC fate from neural progenitors derived from mouse embryonic stem cells (ESCs). CPEC specification by BMP4 was restricted to an early time period after neural induction in culture, with peak CPEC competency correlating to neuroepithelial cells rather than radial glia. In addition to molecular, cellular, and ultrastructural criteria, derived CPECs (dCPECs) had functions that were indistinguishable from primary CPECs, including self-assembly into secretory vesicles and integration into endogenous choroid plexus epithelium following intraventricular injection. We then used BMP4 to generate dCPECs from human ESC-derived neuroepithelial cells. These findings demonstrate BMP4 sufficiency to instruct CPEC fate, expand the repertoire of stem cell-derived neural derivatives in culture, and herald dCPEC-based therapeutic applications aimed at the unique interface between blood, CSF, and brain governed by CPECs.

The sociodemographic and health-related characteristics of a regional population with chronic disease at an interprofessional student-assisted clinic in Queensland Capricornia Allied Health Partnership.

OBJECTIVE: This paper describes the sociodemographic and health-related characteristics of people with chronic disease attending an interprofessional student-assisted clinic in regional Queensland. DESIGN: A retrospective review of data collected during the first 10 months of operation of the clinic was conducted. SETTING, PARTICIPANTS AND OUTCOME MEASURES: Data was collected on up to 378 patients during an intake appointment at the Capricornia Allied Health Partnership (CAHP) community-based clinic and compared with normative reference groups where available. Sociodemographic characteristics included age, gender and education level; health-related characteristics included body mass index and hospitalisations in the previous 12 months; and risk factors included prescribed medications, smoking status and general practitioner-diagnosed medical conditions. RESULTS: Patients attending the CAHP clinic had a mean number of chronic conditions of 4.9 ± 2.1 per patient, and 97% of patients had multimorbidities. A high level of socioeconomic disadvantage was found in comparison with normative comparison groups based on employment, highest level of schooling completed and the index of social disadvantage. Patients predominantly lived in inner regional areas (76.7%). The most common diagnoses of patients attending the clinic for the first time were hypertension, osteoarthritis, high cholesterol, diabetes and chronic back pain. CONCLUSIONS: The CAHP clinic offers a unique student-assisted service model for interprofessional management of patients who are socioeconomically disadvantaged, have multimorbid chronic disease and live in regional areas. The description of baseline data in this paper is important to refine clinic services, to guide other chronic disease clinics and to inform future research study designs.

Experience of a smartphone ambulatory ECG clinic for emergency department patients with palpitation: a single-centre cohort study.

BACKGROUND AND IMPORTANCE: Palpitation is one of the commonest presenting complaints to the emergency department (ED). Diagnosis depends on capturing an ECG during the episode. Unlike syncope, patients retain consciousness and therefore their ability to activate an ECG event recorder. The Investigation of Palpitation in the ED study demonstrated Food and Drug Administration approved AliveCor/Kardia device that links to a smartphone app was safe and effective. A Smartphone Palpitation and Pre-syncope Ambulatory Care Clinic was therefore established. OBJECTIVES: To review the first year of patients attending the service to determine the number and cost-effectiveness of cardiac dysrhythmias diagnoses. DESIGN: Single-center cohort study. SETTINGS AND PARTICIPANTS: Royal Infirmary of Edinburgh, UK. All patients (over 16 years) presenting consecutively to ED with palpitation or pre-syncope, whose ECG was normal, had a compatible device and where an underlying cardiac dysrhythmia was possible were enrolled. INTERVENTION: Ambulatory Care Clinic utilizing the AliveCor/Kardia device. OUTCOME MEASURES AND ANALYSIS: Number diagnosed with cardiac dysrhythmia and mean cost per diagnosis. MAIN RESULTS: Between 24 July 2019 and 23 July 2020, 290 consecutive patients were referred of age 16-80 years (mean 43.3, SD 15.0). One hundred twenty (41.4%) were male. Two hundred thirty-seven (81.7%) were fitted with the device and 220 (75.9%) underwent full investigation. Seventeen of 237 (7.2%) patients had a cardiac diagnosis (12 atrial fibrillation/flutter, 5 supraventricular tachycardia and 1 atrial tachycardia). CONCLUSIONS: There were 17 cardiac diagnoses (7.2%). The cost per symptomatic rhythm diagnosis was 358 GBP (~415 Euro) and the cost per cardiac dysrhythmia diagnosis was 4570 GBP (~5298 Euro). A smartphone-based event recorder clinic should be considered for ED palpitation patients.

Therapeutic vulnerability to PARP1,2 inhibition in RB1-mutant osteosarcoma.

Loss-of-function mutations in the RB1 tumour suppressor are key drivers in cancer, including osteosarcoma. RB1 loss-of-function compromises genome-maintenance and hence could yield vulnerability to therapeutics targeting such processes. Here we demonstrate selective hypersensitivity to clinically-approved inhibitors of Poly-ADP-Polymerase1,2 inhibitors (PARPi) in RB1-defective cancer cells, including an extended panel of osteosarcoma-derived lines. PARPi treatment results in extensive cell death in RB1-defective backgrounds and prolongs survival of mice carrying human RB1-defective osteosarcoma grafts. PARPi sensitivity is not associated with canonical homologous recombination defect (HRd) signatures that predict PARPi sensitivity in cancers with BRCA1,2 loss, but is accompanied by rapid activation of DNA replication checkpoint signalling, and active DNA replication is a prerequisite for sensitivity. Importantly, sensitivity in backgrounds with natural or engineered RB1 loss surpasses that seen in BRCA-mutated backgrounds where PARPi have established clinical benefit. Our work provides evidence that PARPi sensitivity extends beyond cancers identifiable by HRd and advocates PARP1,2 inhibition as a personalised strategy for RB1-mutated osteosarcoma and other cancers.

Improving VTE risk assessment and prophylaxis prescribing rate in medical patients: integrating risk assessment tool into the workflow.

Medical inpatients often have important risk factors for venous thromboembolism (VTE). In our institution, VTE prophylaxis in this group was underused. The main barriers identified were inattention to VTE prophylaxis, competing priorities and lack of confidence in the decision-making. We aimed to improve the rate of VTE prophylaxis use by introducing a paper-based risk assessment tool, with actionable management recommendations within the prescription chart. The rationale was that an assessment tool at the point of prescribing can reduce steps between decision-making and prescribing process, thus promoting confidence and acting as a reminder. A total of 552 prescription charts completed over a period of 29 weeks were examined during the baseline period. In the postintervention period, 871 charts completed over 40 weeks period were examined. The risk assessment tool was completed in 51% of the cases examined in the postintervention period. The introduction of the risk assessment tool was associated with a significant change in the pattern of VTE pharmacological prophylaxis use. The change occurred when the form was made highly visible and enclosed in the prescription chart. The pharmacological prophylaxis use was higher with a completed assessment form than without (mean (SD) 97.5% (7.6%) vs 70.1% (19.4%); p<0.0001). The rate of appropriate prophylaxis decision was 98.2% (SD 5.2%) with a completed assessment form, and 80.7% (SD 17.9%) when it was not used. The qualitative interviews revealed positive themes; many users found it useful, easy and convenient to use. Our data have shown that a paper-based VTE risk assessment tool placed within the prescription chart could substantially improve the rate of appropriate assessment and VTE prophylaxis implementation. This suggests that tool clearly needs to be a seamless integration into the workflow to capture users' attention and mitigate the influence of time perception.

Development of a bioactive paper sensor for detection of neurotoxins using piezoelectric inkjet printing of sol-gel-derived bioinks.

There is an increasing interest in new strategies to rapidly detect analytes of clinical and environmental interest without the need for sophisticated instrumentation. As an example, the detection of acetylcholinesterase (AChE) inhibitors such as neurotoxins and organophosphates has implications for neuroscience, drug assessment, pharmaceutical development, and environmental monitoring. Functionalization of surfaces with multiple reagents, including enzymes and chromogenic reagents, is a critical component for the effective development of "dipstick" or lateral flow biosensors. Herein, we describe a novel paper-based solid-phase biosensor that utilizes piezoelectric inkjet printing of biocompatible, enzyme-doped, sol-gel-based inks to create colorimetric sensor strips. For this purpose, polyvinylamine (PVAm, which captures anionic agents) was first printed and then AChE was overprinted by sandwiching the enzyme within two layers of biocompatible sol-gel-derived silica on paper. AChE inhibitors, including paraoxon and aflatoxin B1, were detected successfully using this sensor by measuring the residual activity of AChE on paper, using Ellman's colorimetric assay, with capture of the 5-thio-2-nitrobenzoate (TNB(-)) product on the PVAm layer. The assay provided good detection limits (paraoxon, approximately 100 nM; aflatoxin B1, approximately 30 nM) and rapid response times (<5 min). Detection could be achieved either by eye or using a digital camera and image analysis software, avoiding the need for expensive and sophisticated instrumentation. We demonstrate that the bioactive paper strip can be used either as a dipstick or a lateral flow-based biosensor. The use of sol-gel-based entrapment produced a sensor that retained enzyme activity and gave reproducible results after storage at 4 degrees C for at least 60 days, making the system suitable for storage and use in the field.

Recent summer warming in northwestern Canada exceeds the Holocene thermal maximum.

Eastern Beringia is one of the few Western Arctic regions where full Holocene climate reconstructions are possible. However, most full Holocene reconstructions in Eastern Beringia are based either on pollen or midges, which show conflicting early Holocene summer temperature histories. This discrepancy precludes understanding the factors that drove past (and potentially future) climate change and calls for independent proxies to advance the debate. We present a ~13.6 ka summer temperature reconstruction in central Yukon, part of Eastern Beringia, using precipitation isotopes in syngenetic permafrost. The reconstruction shows that early Holocene summers were consistently warmer than the Holocene mean, as supported by midges, and a thermal maximum at ~7.6-6.6 ka BP. This maximum was followed by a ~6 ka cooling, and later abruptly reversed by industrial-era warming leading to a modern climate that is unprecedented in the Holocene context and exceeds the Holocene thermal maximum by +1.7 ± 0.7 °C.

Quantifying the Intra-Operative Hemodynamic Effects of Glue Embolization in Vein of Galen Malformations.

Vein of Galen malformation is a rare congenital pathological intracranial arteriovenous shunt which carries 30% risk of death before 28 days-of-age. Treatment is by high risk minimally invasive endovascular glue embolization of shunt feeding arteries under angiographic control. A tool to support intra-operative decision making would be useful. We present a novel method for visualizing angiography data to demonstrate the effect of the intervention based upon change the after embolization in the delay in time of peak contrast density relative to the injected artery and a novel method for quantifying the immediate effect of embolization on the hemodynamics of the shunt. The method is demonstrated on the angiograms of five neonates who underwent embolization. We show consistent results including a post-embolization increase in the delay in time of peak contrast density relative to the injected artery at the venous outflow in keeping with reduced shunting and redistribution of blood following embolization.