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Seasonal influenza immunization reduces the risk of cardiovascular events. Patients with established cardiovascular disease (CVD) derive a greater benefit than those without, yet up to 50 % do not take up the immunization. Patient perceptions and beliefs are known to inform immunization behaviors, yet the immunization related beliefs of patients with CVD have not been described. Objective: To describe beliefs, perceptions and behaviors regarding influenza immunization in patients with CVD. Methods: We undertook a cross-sectional, voluntary and anonymous survey of 181 cardiology inpatients and outpatients attending three large hospitals in Victoria. Results: Median age was 64, 35.0 % were female and 24.2 % spoke a language other than English at home. Over one-third-(34.5 %) of respondents did not receive the seasonal influenza immunization in the prior year. Only half (54.2 %) of patients agreed that their heart condition placed them at higher risk of complications and serious illness if they contracted influenza. Nearly a quarter of patients (24.0 %) were concerned about side effects while 1 in 10 patients raised cost as a barrier despite being free-of-charge in Australia. If asked to receive the seasonal influenza immunization, 86 % patients would agree if their cardiologist recommended it. Conclusion: Despite guideline recommendations, most cardiology patients are uninformed of the cardiovascular benefits of seasonal influenza immunization with many unaware they are at higher risk of influenza-related illness. The vast majority of patients would accept the immunization if recommended by their cardiologist highlighting their important role in improving uptake.

Introduction Central venous access devices (CVADs) are commonly used for the treatment of paediatric cancer patients. Catheter locking is a routine intervention that prevents CVAD-associated adverse events, such as infection, occlusion and thrombosis. While laboratory and clinical data are promising, tetra-EDTA (T-EDTA) has yet to be rigorously evaluated or introduced in cancer care as a catheter lock.Methods and analysis This is a protocol for a two-arm, superiority type 1 hybrid effectiveness-implementation randomised controlled trial conducted at seven hospitals across Australia and New Zealand. Randomisation will be in a 3:2 ratio between the saline (heparinised saline and normal saline) and T-EDTA groups, with randomly varied blocks of size 10 or 20 and stratification by (1) healthcare facility; (2) CVAD type and (3) duration of dwell since insertion. Within the saline group, there will be a random allocation between normal and heparin saline. Participants can be re-recruited and randomised on insertion of a new CVAD. Primary outcome for effectiveness will be a composite of CVAD-associated bloodstream infections (CABSI), CVAD-associated thrombosis or CVAD occlusion during CVAD dwell or at removal. Secondary outcomes will include CABSI, CVAD-associated-thrombosis, CVAD failure, incidental asymptomatic CVAD-associated-thrombosis, other adverse events, health-related quality of life, healthcare costs and mortality. To achieve 90% power (alpha=0.05) for the primary outcome, data from 720 recruitments are required. A mixed-methods approach will be employed to explore implementation contexts from the perspective of clinicians and healthcare purchasers.Ethics and dissemination Ethics approval has been provided by Children’s Health Queensland Hospital and Health Service Human Research Ethics Committee (HREC) (HREC/22/QCHQ/81744) and the University of Queensland HREC (2022/HE000196) with subsequent governance approval at all sites. Informed consent is required from the substitute decision-maker or legal guardian prior to participation. In addition, consent may also be obtained from mature minors, depending on the legislative requirements of the study site. The primary trial and substudies will be written by the investigators and published in peer-reviewed journals. The findings will also be disseminated through local health and clinical trial networks by investigators and presented at conferences.Trial registration number ACTRN12622000499785.

Prior criteria for organ dysfunction in critically ill children were based mainly on expert opinion. We convened the Pediatric Organ Dysfunction Information Update Mandate (PODIUM) expert panel to summarize data characterizing single and multiple organ dysfunction and to derive contemporary criteria for pediatric organ dysfunction. The panel was composed of 88 members representing 47 institutions and 7 countries. We conducted systematic reviews of the literature to derive evidence-based criteria for single organ dysfunction for neurologic, cardiovascular, respiratory, gastrointestinal, acute liver, renal, hematologic, coagulation, endocrine, endothelial, and immune system dysfunction. We searched PubMed and Embase from January 1992 to January 2020. Study identification was accomplished using a combination of medical subject headings terms and keywords related to concepts of pediatric organ dysfunction. Electronic searches were performed by medical librarians. Studies were eligible for inclusion if the authors reported original data collected in critically ill children; evaluated performance characteristics of scoring tools or clinical assessments for organ dysfunction; and assessed a patient-centered, clinically meaningful outcome. Data were abstracted from each included study into an electronic data extraction form. Risk of bias was assessed using the Quality in Prognosis Studies tool. Consensus was achieved for a final set of 43 criteria for pediatric organ dysfunction through iterative voting and discussion. Although the PODIUM criteria for organ dysfunction were limited by available evidence and will require validation, they provide a contemporary foundation for researchers to identify and study single and multiple organ dysfunction in critically ill children.

Abstract Coronavirus disease 2019 (COVID‐19) patients have increased thrombosis risk. With increasing age, there is an increase in COVID‐19 severity. Additionally, adults with a history of vasculopathy have the highest thrombotic risk in COVID‐19. The mechanisms of these clinical differences in risk remain unclear. Human umbilical vein endothelial cells (HUVECs) were infected with SARS‐CoV‐2, influenza A/Singapore/6/86 (H1N1) or mock‐infected prior to incubation with plasma from healthy children, healthy adults or vasculopathic adults. Fibrin on surface of cells was observed using scanning electron microscopy, and fibrin characteristics were quantified. This experiment was repeated in the presence of bivalirudin, defibrotide, low‐molecular‐weight‐heparin (LMWH) and unfractionated heparin (UFH). Fibrin formed on SARS‐CoV‐2 infected HUVECs was densely packed and contained more fibrin compared to mock‐infected cells. Fibrin generated from child plasma was the thicker than fibrin generated in vasculopathic adult plasma (p = 0.0165). Clot formation was inhibited by LMWH (0.5 U/ml) and UFH (0.1–0.7 U/ml). We show that in the context of the SARS‐CoV‐2 infection on an endothelial culture, plasma from vasculopathic adults produces fibrin clots with thinner fibrin, indicating that the plasma coagulation system may play a role in determining the thrombotic outcome of SARS‐CoV‐2 infection. Heparinoid anticoagulants were most effective at preventing clot formation.

While rare, SARS-CoV-2-infected children can develop severe COVID-19 (ARDS) or inflammatory syndrome (MIS-C). Here, the authors use proteomics to characterize hundreds of blood proteins and identify key biological pathways that differentiate MIS-C and ARDS.

Platelets are a key component of the hemostatic system and their roles in inflammation via interactions with leukocytes have also gained attention in recent years. Changes in platelet phenotype and function can cause bleeding and/or thrombosis and, as such, monitoring platelet-specific changes is crucial to assessing hemostasis in the clinical setting. Currently, available platelet function tests such as platelet aggregometry and thromboelastography require a large volume of blood, which is a major limitation for the pediatric population. Whole blood flow cytometric analysis of platelets is increasingly utilized in recent years, primarily due to the sensitivity of this method, but also because it only requires a small amount of blood with minimal sample manipulation. We have developed a whole blood flow cytometry methodological approach that enables the assessment of platelet phenotype, function, and their interactions with monocytes and neutrophils.

This case study explores the processes and challenges of assessing and managing transitional agreements (TAs) at the University of Salford. TAs are contracts with publishers that shift spending from subscriptions to open access and therefore enable the transition to full and immediate open access for research articles. As a teaching-intensive and research-informed university with a small team, Salford needs to ensure that transitional deals are managed effectively and efficiently to maximize our resources and provide the content and publishing opportunities needed to support our teaching and research strategies. Here we describe our processes and the challenges we have faced working remotely and across teams. Finally, we reflect on future developments and how we can continue to adapt and develop our processes as the scholarly landscape evolves.

Snakebite is a globally neglected tropical disease, with coagulation disturbances being the primary pathology of many deadly snake venoms. Age-related differences in human plasma have been abundantly reported, yet the effect that these differences pose regarding snakebite is largely unknown. We tested for differences in coagulotoxic effects (via clotting time) of multiple snake venoms upon healthy human adult (18+) and paediatric (median 3.3 years old) plasma in vivo and compared these effects to the time it takes the plasmas to clot without the addition of venom (the spontaneous clotting time). We tested venoms from 15 medically significant snake species (from 13 genera) from around the world with various mechanisms of coagulotoxic actions, across the three broad categories of procoagulant, pseudo-procoagulant, and anticoagulant, to identify any differences between the two plasmas in their relative pathophysiological vulnerability to snakebite. One procoagulant venom (Daboia russelii, Russell’s Viper) produced significantly greater potency on paediatric plasma compared with adult plasma. In contrast, the two anticoagulant venoms (Pseudechis australis, Mulga Snake; and Bitis cornuta, Many-horned Adder) were significantly more potent on adult plasma. All other procoagulant venoms and all pseudo-procoagulant venoms displayed similar potency across both plasmas. Our preliminary results may inform future studies on the effect of snake venoms upon plasmas from different age demographics and hope to reduce the burden of snakebite upon society.

The Fontan circulation introduces an increased risk of thromboembolism which is associated with substantial mortality and morbidity. Adverse outcomes of thromboembolic complications post-Fontan surgery vary in both nature and severity, ranging from local tissue infarction and pulmonary embolism to Fontan failure and ischemic stroke. Furthermore, recent studies have identified that subclinical stroke is common yet underdiagnosed in Fontan patients. Fontan patients are commonly treated with antiplatelet agents and/or anticoagulants as primary thromboprophylaxis. Optimal thromboprophylaxis management in the Fontan population is still unclear, and clinical consensus remains elusive despite the growing literature on the subject. This perspective will describe the nature of thromboembolism post-Fontan surgery and provide evidence for the use of both current and emerging thromboprophylaxis options for children and adults living with Fontan circulation.

Abstract Objectives Extracorporeal membrane oxygenation (ECMO) involves complex coagulation management and frequent hemostatic complications. ECMO practice between centers is variable. To compare results between coagulation studies, standardized definitions and clear documentation of ECMO practice is essential. We assessed how study population, outcome definitions, and ECMO‐, coagulation‐, and transfusion‐related parameters were described in pediatric ECMO studies. Data sources Embase, Medline, Web of Science, Cochrane Library and Google Scholar. Study selection English original studies of pediatric ECMO patients describing hemostatic tests or outcome. Data extraction Eligibility was assessed following PRISMA guidelines. Study population, outcome and ECMO‐, coagulation, and transfusion parameters were summarized. Data synthesis A total of 107 of 1312 records were included. Study population parameters most frequently included (gestational) age (79%), gender (60%), and (birth) weight (59%). Outcomes, including definitions of bleeding (29%), thrombosis (15%), and survival (43%), were described using various definitions. Description of pump type, oxygenator and cannulation mode occurred in 49%, 45%, and 36% of studies, respectively. The main coagulation test (53%), its reference ranges (49%), and frequency of testing (24%) were the most prevalent reported coagulation parameters. The transfusion thresholds for platelets, red blood cells, and fibrinogen were described in 27%, 18%, and 18% of studies, respectively. Conclusions This systematic review demonstrates a widespread lack of detail or standardization of several parameters in coagulation research of pediatric ECMO patients. We suggest several parameters that might be included in future coagulation studies. We encourage the ECMO community to adopt and refine this list of parameters and to use standardized definitions in future research.

Flow cytometry is a valuable tool in determining the phenotype and function of platelets accurately. The emergence of platelet flow cytometry in recent years provides an attractive alternative to other platelet analytical techniques, with advantages such as requiring small volumes and being highly sensitive to minimal changes in receptor function and expression. Here we present a methodical approach encompassing the stages in the development and optimization of platelet flow cytometry panels based on our extensive experience in this area.

Abstract This ISTH “State of the Art” review aims to critically evaluate the hematologic considerations and complications in extracorporeal membrane oxygenation (ECMO). ECMO is experiencing a rapid increase in clinical use, but many questions remain unanswered. The existing literature does not address or explicitly state many pertinent details that may influence hematologic complications and, ultimately, patient outcomes. This review aims to broadly introduce modern ECMO practices, circuit designs, circuit materials, hematologic complications, transfusion‐related considerations, age‐ and size‐related differences, and considerations for choosing outcome measures. Relevant studies from the 2019 ISTH Congress in Melbourne, which further advanced our understanding of these processes, will also be highlighted.

SARS-CoV-2 is the causative agent of the COVID-19 pandemic. Vaccination, supported by social and public health measures, has proven efficacious for reducing disease severity and virus spread. However, the emergence of highly transmissible viral variants that escape prior immunity highlights the need for additional mitigation approaches. Heparin binds the SARS-CoV-2 spike protein and can inhibit virus entry and replication in susceptible human cell lines and bronchial epithelial cells. Primary infection predominantly occurs via the nasal epithelium, but the nasal cell biology of SARS-CoV-2 is not well studied. We hypothesized that prophylactic intranasal administration of heparin may provide strain-agnostic protection for household contacts or those in high-risk settings against SARS-CoV-2 infection. Therefore, we investigated the ability of heparin to inhibit SARS-CoV-2 infection and replication in differentiated human nasal epithelial cells and showed that prolonged exposure to heparin inhibits virus infection. Furthermore, we establish a method for PCR detection of SARS-CoV-2 viral genomes in heparin-treated samples that can be adapted for the detection of viruses in clinical studies.

Children have reduced severity of COVID-19 compared to adults and typically have mild or asymptomatic disease. The immunological mechanisms underlying these age-related differences in clinical outcomes remain unexplained. Here, we quantify 23 immune cell populations in 141 samples from children and adults with mild COVID-19 and their PCR-negative close household contacts at acute and convalescent time points. Children with COVID-19 displayed marked reductions in myeloid cells during infection, most prominent in children under the age of five. Recovery from infection in both children and adults was characterised by the generation of CD8 TCM and CD4 TCM up to 9 weeks post infection. SARS-CoV-2-exposed close contacts also had immunological changes over time despite no evidence of confirmed SARS-CoV-2 infection on PCR testing. This included an increase in low-density neutrophils during convalescence in both exposed children and adults, as well as increases in CD8 TCM and CD4 TCM in exposed adults. In comparison to children with other common respiratory viral infections, those with COVID-19 had a greater change in innate and T cell-mediated immune responses over time. These findings provide new mechanistic insights into the immune response during and after recovery from COVID-19 in both children and adults.

Background and objective Serum iron results are not indicative of iron deficiency yet may be incorrectly used to diagnose iron deficiency instead of serum ferritin results. Our objective was to determine the association between serum iron test results and iron-deficiency diagnosis in children by general practitioners.Design, setting, patients and main outcome measures A retrospective observational study of 14 187 children aged 1–18 years with serum ferritin and serum iron test results from 137 general practices in Victoria, Australia, between 2008 and 2018. Generalised estimating equation models calculating ORs were used to determine the association between serum iron test results (main exposure measure) and iron-deficiency diagnosis (outcome measure) in the following two population groups: (1) iron-deplete population, defined as having a serum ferritin 30 µg/L.Results 3484 tests were iron deplete and 15 528 were iron replete. Iron-deplete children were less likely to be diagnosed with iron deficiency if they had normal serum iron levels (adjusted OR (AOR): 0.73; 95% CI 0.57 to 0.96). Iron-replete children had greater odds of an iron-deficiency diagnosis if they had low serum iron results (AOR: 2.59; 95% CI 1.72 to 3.89). Other contributors to an iron-deficiency diagnosis were female sex and having anaemia.Conclusion Serum ferritin alone remains the best means of diagnosing iron deficiency. Reliance on serum iron test results by general practitioners is leading to significant overdiagnosis and underdiagnosis of iron deficiency in children.

Abstract Background The EINSTEIN-Jr program will evaluate rivaroxaban for the treatment of venous thromboembolism (VTE) in children, targeting exposures similar to the 20 mg once-daily dose for adults. Methods This was a multinational, single-dose, open-label, phase I study to describe the pharmacodynamics (PD), pharmacokinetics (PK) and safety of a single bodyweight-adjusted rivaroxaban dose in children aged 0.5–18 years. Children who had completed treatment for a venous thromboembolic event were enrolled into four age groups (0.5–2 years, 2–6 years, 6–12 years and 12–18 years) receiving rivaroxaban doses equivalent to 10 mg or 20 mg (either as a tablet or oral suspension). Blood samples for PK and PD analyses were collected within specified time windows. Results Fifty-nine children were evaluated. In all age groups, PD parameters (prothrombin time, activated partial thromboplastin time and anti-Factor Xa activity) showed a linear relationship versus rivaroxaban plasma concentrations and were in line with previously acquired adult data, as well as in vitro spiking experiments. The rivaroxaban pediatric physiologically based pharmacokinetic model, used to predict the doses for the individual body weight groups, was confirmed. No episodes of bleeding were reported, and treatment-emergent adverse events occurred in four children and all resolved during the study. Conclusions Bodyweight-adjusted, single-dose rivaroxaban had predictable PK/PD profiles in children across all age groups from 0.5 to 18 years. The PD assessments based on prothrombin time and activated partial thromboplastin time demonstrated that the anticoagulant effect of rivaroxaban was not affected by developmental hemostasis in children. Trial registration ClinicalTrials.gov number, NCT01145859.

Abstract Background Venous thromboembolism (VTE) is a relatively rare condition in childhood with treatment mainly based on extrapolation from studies in adults. Therefore, clinical trials of anticoagulation in children require novel approaches to deal with numerous challenges. The EINSTEIN-Jr program identified pediatric rivaroxaban regimens commencing with in vitro dose finding studies followed by evaluation of children of different ages through phase I and II studies using extensive modeling to determine bodyweight-related doses. Use of this approach resulted in drug exposure similar to that observed in young adults treated with rivaroxaban 20 mg once-daily. Methods EINSTEIN-Jr phase III is a randomized, open-label, study comparing the efficacy and safety of rivaroxaban 20 mg-equivalent dose regimens with those of standard anticoagulation for the treatment of any types of acute VTE in children aged 0–18 years. A total of approximately 500 children are expected to be included during the 4-year study window. Flexibility of treatment duration is allowed with study treatment to be given for 3 months with the option to continue treatment in 3-month increments, up to a total of 12 months. However, based on most common current practice, children younger than 2 years with catheter-related thrombosis will have a main treatment period of 1 month with the option to prolong treatment in 1-month increments, up to a total of 3 months. Conclusions EINSTEIN-Jr will compare previously established 20 mg-equivalent rivaroxaban dosing regimens with standard anticoagulation for the treatment of VTE in children. Demonstration of similarity of disease, as well as equivalent rivaroxaban exposure and exposure-response will enable extrapolation of efficacy from adult trials, which is critical given the challenges of enrollment in pediatric anticoagulation trials. Trial registration Clinicaltrials.gov NCT02234843, registered on 9 September 2014.

Abstract Background Venous thromboembolism (VTE) in young children is not well documented. Methods Clinicians from 12 institutions retrospectively evaluated the presentation, therapeutic management, and outcome of VTE in children younger than 2 years seen in 2011–2016. Feasibility of recruiting these children in EINSTEIN-Jr. phase III, a randomized trial evaluating rivaroxaban versus standard anticoagulation for VTE, was assessed. Results We identified 346 children with VTE, of whom 227 (65.6%) had central venous catheter-related thrombosis (CVC-VTE), 119 (34.4%) had non-CVC-VTE, and 156 (45.1%) were younger than 1 month. Of the 309 children who received anticoagulant therapy, 86 (27.8%) had a short duration of therapy (i.e.

Abstract: Pregnancies affected by preeclampsia (PE) or fetal growth restriction (FGR) display increases in thrombin generation and reductions in angiogenesis and cell growth. There is significant interest in the potential for low molecular weight heparins (LMWHs) to reduce the recurrence of PE and FGR. However, LMWH is associated with an increased risk of bleeding. Therefore, it is of vital importance to determine the exact molecular function of heparins in pregnancy if they are used as therapy for pregnant women. We aimed to determine this using our model for PE/FGR in microvascular endothelial cells. The expression of decorin, a proteoglycan, was reduced to mimic PE/FGR in these cells compared with controls. Four concentrations of unfractionated heparin (UFH), LMWH, and nonanticoagulant heparin (NAC) were added to determine the effect on thrombin generation, angiogenesis, and cell growth. Treatment with UFH and LMWH reduced thrombin generation and restored angiogenesis but decreased cell growth. Treatment with NAC did not affect thrombin generation, restored angiogenesis, and showed a trend toward cell growth. In conclusion, treatment with NAC produced the same, if not better, results as treatment with UFH or LMWH, without the same impact on coagulation. Therefore, NAC could potentially be a better therapeutic option for prevention of PE/FGR in high-risk women, without the risk of the adverse effects of traditional anticoagulants.

Background: Despite increasing technical improvement and extracorporeal membrane oxygenation (ECMO)-related knowledge over the past three decades, morbidity and mortality associated with bleeding and clotting complications remain high in pediatric patients undergoing ECMO. Platelets, a key element of the coagulation system, have been proposed to be the main cause of coagulopathy in the setting of ECMO. This systematic review aims to summarize and discuss the existing knowledge of platelet phenotype and function in the pediatric ECMO population.Methods: A systematic review was conducted for the Embase, Medline, and PubMed databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines.Results: The detailed study selection process yielded a total of 765 studies and only 3 studies that fulfilled the selection criteria were included in this review. Techniques used to assess platelet function in the three existing studies included platelet aggregometry, flow cytometry, and thromboelastography-platelet mapping. The finding that is common to the three studies is reduced platelet function in pediatric patients during ECMO either compared to before the initiation of ECMO or in non-survivors compared to survivors. Two studies demonstrated reduced platelet aggregation that are irreversible by platelet transfusion during ECMO. Two studies reported bleeding events and mortality in children on ECMO and none of the studies investigated thrombotic events.Conclusions: This systematic review demonstrates the extremely limited information available for platelet phenotype and function in the pediatric ECMO population. Evidence from the existing literature suggests reduced platelet aggregation and increased platelet activation in children during ECMO. However, this needs to be interpreted with care due to the limitations associated with the techniques used for platelet function testing. Furthermore, the association between platelet dysfunction and clinical outcomes in the pediatric ECMO population remains elusive. Multiple research gaps have been identified when it comes to the knowledge of platelet phenotype and function of children on ECMO, highlighting the need for robust, well-designed studies in this setting.

Background: The intestinal vitamin D receptor (VDR) remains poorly characterized in patients with inflammatory bowel disease (IBD). Methods: Colonoscopic biopsies and intestinal resection specimens from the terminal ileum, ascending and sigmoid colon, from patients with and without IBD, were analyzed for VDR mRNA quantification by polymerase chain reaction, and protein localization and semi-quantification by immunohistochemistry. The relationship between VDR and intestinal inflammation, serum 25(OH)D and oral vitamin D intake was elicited. Results: A total of 725 biopsies from 20 patients with Crohn’s disease (CD), 15 with ulcerative colitis (UC) and 14 non-IBD controls who underwent colonoscopy were studied. VDR gene expression and protein staining intensity was similar across all three groups, and across the intestinal segments. Sigmoid colon VDR mRNA expression inversely correlated with faecal calprotectin ( r = −0.64, p = 0.026) and histological score ( r = −0.67, p = 0.006) in UC, and histological score ( r = −0.58, p = 0.019) in patients with CD. VDR staining intensity was higher in quiescent than diseased segments. No relationship with serum 25(OH)D or oral vitamin D intake was noted. Immunohistochemical staining of 28 intestinal resection specimens from 15 patients (5 each with CD, UC and non-IBD controls) showed diffuse VDR staining in the mucosa, submucosa and circular muscle. Conclusions: VDR transcript expression and protein staining intensity are inversely related to inflammation in IBD, but unrelated to serum 25(OH)D, and similar to non-IBD controls. Strategies to upregulate intestinal VDR, potentially translating to modulation of disease activity, require investigation.

The accumulation of blood proteins and cells on extracorporeal membrane oxygenation (ECMO) circuits has been proposed as a contributing factor to the coagulopathic state of many patients. This systematic review aims to summarize and discuss the existing knowledge of blood components binding to the ECMO circuits in human patients. A systematic review was conducted using the Medline, PubMed and Embase databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Seven studies were included in this review. Three studies identified a leukocyte adhesion, three studies observed von Willebrand factor accumulation and four studies identified bound platelets on the surface of the circuits. Other identified components included fibrin, albumin, hemoglobin, erythrocytes, progenitor cells, fibronectin and IgG. This systematic review demonstrates the limited state of knowledge when it comes to adsorption to the ECMO circuits in humans. Most of the studies lacked insight or detail into the mechanisms of binding and the interactions between different components bound to the ECMO circuits. Further research is required to comprehensively characterize surface adsorption to ECMO circuits in humans and to define the specific mechanisms of binding, enabling improvements that increase biocompatibility between the blood-circuit interface in this important clinical setting.

Domesticated animals in the prehispanic American Southwest/Mexican Northwest functioned in many roles, but these roles seem to have varied across time and space. In this study, we use bone collagen and apatite carbon (δ13Ccol/ap) and nitrogen (δ15N) stable isotopes to investigate the role(s) of seven canids from Arroyo Hondo Pueblo (LA 12), a 14th century site in the northern Rio Grande, New Mexico. Results indicate that in some cases, coyotes seem to have been treated like dogs; in others, dogs seem to have been treated like their wild relatives. In all cases, canids were treated differently than domestic turkeys. We conclude that ethnographic, genetic, geochemical and site-specific contextual data are required to understand the roles of dogs and wild canids in Ancestral Puebloan contexts. Social Media: New isotopic data, combined with previously published provenience and a DNA information, suggest different classifications of canids by Ancestral Puebloans at Arroyo Hondo Pueblo.

Background: Pulmonary hypertension (PH) in pregnancy is associated with a high maternal mortality and morbidity and has been found to be as high as 30-56%. Aim: To review the management of such patients in a tertiary center over a 15 year period, as the current literature consists of a few case reports, a few small case series and 2 meta-analyses. Materials and Methods: A review of all patients admitted to our institution for management of PH in pregnancy between 1994 and February 2009 was undertaken. Cases were identified from the high-risk pregnancy database within the department of anesthesia and from the hospital medical records. Severity of PH, type of PH, NYHA functional status at presentation and delivery, mode of delivery, peripartum monitoring and APGAR scores were noted. Patients were reviewed by a multidisciplinary team and management planned accordingly. Results: 19 eligible patients were identified. Patients who were significantly sick due to their PH were aggressively managed during pregnancy. Overall there was an improvement in NYHA functional status at the time of delivery. Epidural analgesia and anesthesia for labor and operatively delivery seem to be the ideal choice. Conclusion: Multidisciplinary approach is a key to the successful management of these patients. Secondary PH results in higher morbidity and mortality, in particular, older the age higher the maternal morbidity and mortality.

This article reads the papal encyclical as a genre in political thought. As a form, the encyclical authorizes itself through the ontological surety provided by Christian revelation, juxtaposed with an intervention into contemporary and contested politics. As explicitly theological texts, encyclicals trouble normative notions of the political. At the same time, however, they do significant political work in the world. This article reads the genre as a form, attempting to disaggregate the theological and the political inhering within, while recognizing their inextricability. The object of the article is, thus, to reckon with the encyclical, and to take it seriously in the post-secular.

The bovine paranasal sinuses are a group of complex cavernous air-filled spaces, lined by respiratory epithelium, the exact function of which is unclear. While lesions affecting these sinuses are occasionally reported in cattle, their microbial flora has not been defined. Furthermore, given that the various bacterial and viral pathogens causing bovine respiratory disease (BRD) persist within herds, we speculated that the paranasal sinuses may serve as a refuge for such infectious agents. The paranasal sinuses of clinically normal cattle (n = 99) and of cattle submitted for post-mortem examination (PME: n = 34) were examined by microbial culture, PCR and serology to include bacterial and viral pathogens typically associated with BRD: Mycoplasma bovis, Histophilus somni, Mannheimia haemolytica and Pasteurella multocida, bovine respiratory syncytial virus (BRSV) and bovine parainfluenza-3 virus (BPIV-3). Overall, the paranasal sinuses were either predominantly sterile or did not contain detectable microbes (83.5%: 94.9% of clinically normal and 50.0% of cattle submitted for PME). Bacteria, including BRD causing pathogens, were identified in relatively small numbers of cattle (