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Background: Optimal composition and infusion rates of intravenous maintenance fluids for children undergoing surgery are not well defined. Avoidance of hypoglycaemia, ketosis, and hyponatraemia is important, and current guidelines recommend isotonic fluids containing 1.0-2.5% glucose. However, evidence for its safe use in infants is insufficient. The aim of this study was to investigate whether normoglycaemia is maintained in infants using a balanced electrolyte maintenance infusion with 1% glucose., Methods: Infants 1-12 months of age undergoing surgery were included in this prospective two-centre study. Intravenous maintenance fluid was given with infusion rates of 4-8 ml kg -1 h -1 . Blood gas and ketone body analysis were performed at induction and at the end of anaesthesia. Plasma glucose concentration was monitored intraoperatively., Results: For the 365 infants included in this study, the median infusion rate of maintenance fluid was 3.97 (interquartile range 3.21-5.35) ml kg -1 h -1 . Mean plasma glucose concentration increased from 5.3 mM at induction to 6.1 mM at the end of anaesthesia (mean difference 0.8 mM; 95% confidence interval 0.6-0.9, P<0.001). No cases of hypoglycaemia (<3.0 mM) occurred. Mean sodium concentration remained stable during anaesthesia. Chloride and ketone body concentration increased and base excess decreased, but these were within the normal range., Conclusions: In infants undergoing surgery, maintenance infusion with a balanced electrolyte solution containing 1% glucose, at rates similar to those proposed by Holliday and Segar is a safe alternative with regards to homeostasis of glucose, electrolytes, and acid-base balance., Clinical Trial Registration: ACTRN12619000833167., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Coral reefs are facing threats from a variety of global change stressors, including ocean warming, acidification, and deoxygenation. It has been hypothesized that growing corals near primary producers such as macroalgae or seagrass may help to ameliorate acidification and deoxygenation stress, however few studies have explored this effect in situ. Here, we investigated differences in coral growth rates across a natural gradient in seawater temperature, pH, and dissolved oxygen (DO) variability in a nearshore seagrass bed on Dongsha Atoll, Taiwan, South China Sea. We observed strong spatial gradients in temperature (5°C), pH (0.29 pH units), and DO (129 μmol O2 kg-1) across the 1-kilometer wide seagrass bed. Similarly, diel variability recorded by an autonomous sensor in the shallow seagrass measured diel ranges in temperature, pH, and DO of up to 2.6°C, 0.55, and 204 μmol O2 kg-1, respectively. Skeletal cores collected from 15 massive Porites corals growing in the seagrass bed at 4 sites revealed no significant differences in coral calcification rates between sites along the gradients. However, significant differences in skeletal extension rate and density suggest that the dynamic temperature, pH, and/or DO variability may have influenced these properties. The lack of differences in coral growth between sites may be because favorable calcification conditions during the day (high temperature, pH, and DO) were proportionally balanced by unfavorable conditions during the night (low temperature, pH, and DO). Alternatively, other factors were simply more important in controlling coral calcification and/or corals were acclimated to the prevailing conditions at each site., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Pezner et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Mixed venous oxygen saturation (SvO 2 ) is a critical variable in the assessment of oxygen supply and demand but is rarely used in children due to the invasive nature of pulmonary artery catheters. The aim of this prospective, observational study was to investigate the accuracy of noninvasively measured SvO 2 acquired by the novel capnodynamic method, based on differential Fick equation (Capno-SvO 2 ), against gold standard CO-oximetry., Methods: Capno-SvO 2 was compared to SvO 2 measured by pulmonary artery blood gas CO-oximetry in children undergoing cardiac catheter interventions and subjected to moderate hemodynamic challenges. Bland-Altman analysis was used to describe the agreement of absolute values between CO-oximetry and Capno-SvO 2 , and a concordance rate was calculated to evaluate the ability of Capno-SvO 2 to track change., Results: Twenty-five procedures were included in the study. Capno-SvO 2 showed a bias toward CO-oximetry of +3 percentage points; upper and lower limits of agreement were +11 percentage points (95% confidence interval [CI], 9-14) and -5 percentage points (95% CI, -8 to -3), respectively. The concordance rate was 92% (95% CI, 89-96)., Conclusions: In conclusion, this first clinical application of a novel concept for noninvasive SvO 2 monitoring without the need for a pulmonary artery catheter indicates that Capno-SvO 2 generates absolute values and trending capacity in close agreement with the gold standard reference method., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2024 International Anesthesia Research Society.)

The use of outpatient parenteral antimicrobial therapy (OPAT) for children has several advantages, including reduced length of hospital stay and costs. A reliable vascular access is key to delivering safe and effective pediatric OPAT. In recent years, midline catheters (MC) have been increasingly used for short-term intravenous antibiotic therapy in children. However, there are no studies investigating the use of MCs in the OPAT setting. The main aim of this paper was to evaluate the success and complications of using MCs for pediatric OPAT. This was a retrospective cohort study from a tertiary academic pediatric hospital. All MCs inserted at the hospital and used for OPAT were eligible for study inclusion. The primary objective was to describe the percentage of patients able to complete OPAT without the need for additional venous access. Forty-one MCs were included in the study. Patient mean (SD) age was 5.9 (4.9) years. In 31 cases (76%, 95% CI 62-86%), the iv therapy could be successfully completed using only the MC. Imbalances between the groups suggested unfavorable outcome for saphenous vein catheters as well as for shorter and smaller-sized catheters. Fourteen patients (34%) were subjected to a MC-related complication. Pain on injection in the MC was the most frequent complication (n = 10, 24%).    Conclusion: Midline catheters could be an alternative to central venous access for pediatric OPAT. Avoiding saphenous vein insertion and using longer and larger-sized catheters could increase MC success rate. No severe MC-related complication was found. Further randomized studies comparing different catheter types are needed. What is Known: • For selected patients, pediatric outpatient parenteral antimicrobial therapy (OPAT) is safe and provides health-economic, psychosocial, and medical advantages compared to in-hospital care. • A reliable venous access is one of the key factors to the success of OPAT, but this can be a challenge in children. What is New: • Using midline catheters, 76% of patients could complete their intended iv therapy without the need for additional venous access. Avoiding saphenous vein insertion and using longer and larger-sized catheters could increase the success rate. • Thirty-four percent of catheters were subject to some kind of complication, the most common being pain on injection in the catheter., (© 2024. The Author(s).)

Background: Midline catheters are peripheral intravenous (IV) catheters in which the tip of the catheter does not reach the central circulation. In children, the use of midline catheters could lead to decreased complications from central venous catheters. To validate the safety of midline catheter use in children, we aimed to describe the complications and dwell time of pediatric midline catheters. The primary outcome was the incidence of catheter-related venous thromboembolism (VTE)., Methods: We conducted an observational, prospective study including consecutive patients at a tertiary multidisciplinary pediatric hospital. One hundred pediatric midline catheters were followed for thrombotic, infectious, and mechanical complications. After catheter removal, Doppler ultrasonography was performed to detect asymptomatic VTE., Results: The mean age was 6.0 years (standard deviation [SD], 4.7), and median catheter dwell time was 6 (4-8) days. Most midline catheters were inserted in arm veins, most commonly in the basilic vein (56%). Catheter-related VTE was diagnosed in 30 (30%; 95% confidence interval [CI], 21%-40%) cases, corresponding to an incidence rate of 39 (95% CI, 26-55) cases per 1000 catheter days. Eight of 14 saphenous vein catheters were complicated by VTE compared to 22 of 86 arm vein catheters, suggesting an imbalance in favor of arm vein insertion site. Two patients needed anticoagulation therapy due to catheter-related VTE. Thirty (30%) catheters were removed unintentionally or due to complications, 22 of these needed additional IV access to complete the intended therapy. No catheter-related bloodstream infection (95% CI, 0%-4%) occurred. Mechanical complications occurred in 33 (33%; 95% CI, 24%-43%) midline catheters., Conclusions: In children, thrombotic and mechanical complications of midline catheters are common, but only few VTEs are severe enough to warrant anticoagulation therapy. Systemic infectious complications are rare. Seventy-eight percent of patients did not need additional venous access to complete short-term IV therapy. Considering the rate of clinically relevant complications and the catheter dwell time, pediatric midline catheters could be an alternative to central venous access for short-term (5-10 days) IV therapy., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 International Anesthesia Research Society.)

Coastal upwelling regions are among the most productive marine ecosystems but may be threatened by amplified ocean acidification. Increased acidification is hypothesized to reduce iron bioavailability for phytoplankton thereby expanding iron limitation and impacting primary production. Here we show from community to molecular levels that phytoplankton in an upwelling region respond to short-term acidification exposure with iron uptake pathways and strategies that reduce cellular iron demand. A combined physiological and multi-omics approach was applied to trace metal clean incubations that introduced 1200 ppm CO 2 for up to four days . Although variable, molecular-level responses indicate a prioritization of iron uptake pathways that are less hindered by acidification and reductions in iron utilization. Growth, nutrient uptake, and community compositions remained largely unaffected suggesting that these mechanisms may confer short-term resistance to acidification; however, we speculate that cellular iron demand is only temporarily satisfied, and longer-term acidification exposure without increased iron inputs may result in increased iron stress., (© 2023. The Author(s).)

Objectives: Supraglottoplasty (SGP) for severe laryngomalacia (LM) in children with medical comorbidities has been associated with high risk of surgical failure and increased need of postoperative pediatric intensive care unit (PICU) intervention, but evidence for this is ambiguous. The objective was to evaluate surgical outcome and risk of need for PICU-intervention following SGP for severe LM in comorbid patients., Methods: Retrospective observational study of 116 patients treated with SGP for severe LM between 2000 and 2021 at a tertial referral pediatric airway surgery center Karolinska University Hospital. Medical records were reviewed and patient data regarding surgical timing, type of SGP procedure, PICU-intervention, complications, and outcomes were recorded. Patients were defined as non-comorbid vs high-risk comorbid (HRC) based on a coexisting comorbidity for risk of surgical failure and postoperative PICU-intervention. Surgical failure was defined as need of revision surgery, tracheostomy or assisted ventilation (continuous positive airway pressure and bilevel positive airway pressure). PICU intervention was defined as need of postoperative assisted ventilation or intubation. Statistical comparisons were performed with outcome of SGP on children with LM and no comorbidities., Results: 41/116 patients included had a HRC associated with an increased risk of PICU-intervention and surgical failure. 75/116 patients were defined as non-comorbid. The overall surgical success in the study population was 89.7% (104/116), 94.7% in the non HRC group vs 80.5% in the HRC-group. 5/41 HRC patients and 1/75 non-comorbid patients needed SGP revision in which 5/6 was successful. There was no significantly increased need for postoperative PICU intervention in HRC patients., Conclusion: SGP for severe LM patients with high-risk comorbidities performed in a tertiary setting had an overall good result and low risk of PICU-intervention. Revision SGP was more common in HRC patients but had a good outcome. Multidisciplinary experience in perioperative care of comorbid patients may be of key importance for outcome and children with high-risk comorbidities should thus not be withheld the possible benefit of SGP without assessment at a tertiary pediatric airway center., Competing Interests: Declaration of competing interest No conflicts of interests were reported from any of the authors., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

We investigated whether CO 2 -induced ocean acidification (OA) affects dopamine receptor-dependent behavior in bicolor damselfish (Stegastes partitus). Damselfish were kept in aquaria receiving flow through control (pH ~ 8.03; pCO 2  ~ 384 μatm) or OA (pH ~ 7.64; CO 2  ~ 1100 μatm) seawater at a rate of 1 L min -1 . Despite this relatively fast flow rate, fish respiration further acidified the seawater in both control (pH ~7.88; pCO 2  ~ 595 μatm) and OA (pH ~7.55; pCO 2  ~ 1450 μatm) fish-holding aquaria. After five days of exposure, damselfish locomotion, boldness, anxiety, and aggression were assessed using a battery of behavioral tests using automated video analysis. Two days later, these tests were repeated following application of the dopamine D 1 receptor agonist SKF 38393. OA-exposure induced ceiling anxiety levels that were significantly higher than in control damselfish, and SKF 38393 increased anxiety in control damselfish to a level not significantly different than that of OA-exposed damselfish. Additionally, SKF 38393 decreased locomotion and increased boldness in control damselfish but had no effect in OA-exposed damselfish, suggesting an alteration in activity of dopaminergic pathways that regulate behavior under OA conditions. These results indicate that changes in dopamine D 1 receptor function affects fish behavior during exposure to OA. However, subsequent measurements of seawater sampled using syringes during the daytime (~3-4 pm local time) from crevasses in coral reef colonies, which are used as shelter by damselfish, revealed an average pH of 7.73 ± 0.03 and pCO 2 of 925.8 ± 62.2 μatm; levels which are comparable to Representative Concentration Pathway (RCP) 8.5 predicted end-of-century mean OA levels in the open ocean. Further studies considering the immediate environmental conditions experienced by fish as well as individual variability and effect size are required to understand potential implications of the observed OA-induced behavioral effects on damselfish fitness in the wild., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The organization of healthcare could have an impact on the outcome of patients treated for acute cholecystitis (AC). The aim of this study was to analyze the way in which patients with AC are managed relative to the level of care by the treating hospital., Methods: Data were collected from the Swedish Register for Gallstone Surgery and ERCP (GallRiks). Cholecystectomies between 2010 and 2019 were included. The inclusion criterion was acute cholecystectomy in patients with AC operated at either tertiary referral centers (TRCs) or regional hospitals., Results: A total of 24,194 cholecystectomies with AC met the inclusion criterion. The time between admission and acute surgery was significantly elongated at TRCs compared with regional hospitals (2.2 ± 1.7 days vs. 1.6 ± 1.4 days, mean ± SD; p < 0.0001). Patients with a history of AC were more frequent at TRC (10.1% vs. 8.9%, p < 0.0056) and had a higher adverse event rate compared with those at regional hospitals (OR 1.61; CI 1.40-1.84, p < 0.0001). Surprisingly, an increased number of hospital beds correlated slightly with an increased number of days between admission and surgery (R 2  = 0.132; p = 0.0075)., Conclusion: Compared with regional hospitals, patients with AC had to wait longer at TRCs before surgery. A history of AC significantly increased the risk of adverse events. These findings indicate that logistic and organizational aspects of hospital care may affect the management of patients with AC. However, whether these findings can be generalized to healthcare organizations outside Sweden requires further investigation., (© 2022. The Author(s).)

The California Current System experiences seasonal ocean acidification and hypoxia (OAH) owing to wind-driven upwelling, but little is known about the intensity, frequency, and depth distribution of OAH in the shallow nearshore environment. Here we present observations of OAH and dissolved inorganic carbon and nutrient parameters based on monthly transects from March 2017 to September 2018 extending from the surf zone to the ~ 40 m depth contour in La Jolla, California. Biologically concerning OAH conditions were observed at depths as shallow as 10 m and as close as 700 m to the shoreline. Below 20 m depth, 8% of observations were undersaturated with respect to aragonite, 28% of observations had a pH T less than 7.85, and 19% of observations were below the sublethal oxygen threshold of 157 µmol kg -1 . These observations raise important questions about the impacts of OAH on coastal organisms and ecosystems and how future intensified upwelling may exacerbate these conditions., (© 2022. The Author(s).)

In this study, we demonstrated the first, to our knowledge, integrated continuous bioprocess (ICB) designed for the production of acid-sensitive monoclonal antibodies, prone to aggregate at low pH, on pilot scale. A high cell density perfusion culture, stably maintained at 100 × 10 6  cells/ml, was integrated with the downstream process, consisting of a capture step with the recently developed Protein A ligand, Z Ca ; a solvent/detergent-based virus inactivation; and two ion-exchange chromatography steps. The use of a mild pH in the downstream process makes this ICB suitable for the purification of acid-sensitive monoclonal antibodies. Integration and automation of the downstream process were achieved using the Orbit software, and the same equipment and control system were used in initial small-scale trials and the pilot-scale downstream process. High recovery yields of around 90% and a productivity close to 1 g purified antibody/L/day were achieved, with a stable glycosylation pattern and efficient removal of impurities, such as host cell proteins and DNA. Finally, negligible levels of antibody aggregates were detected owing to the mild conditions used throughout the process. The present work paves the way for future industrial-scale integrated continuous biomanufacturing of all types of antibodies, regardless of acid stability., (© 2022 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals LLC.)

The risk for venous thromboembolism (VTE) is considered to be low in the general paediatric intensive care unit (PICU) population, and pharmacological thromboprophylaxis is not routinely used. PICU patients considered at high-risk of VTE could possibly benefit from pharmacological thromboprophylaxis, but the incidence of VTE in this group of patients is unclear. This was an observational, prospective study at a tertiary multi-disciplinary paediatric hospital. We used comprehensive ultrasonography screening for VTE in critically ill children with multiple risk factors for VTE. Patients admitted to PICU ≥ 72 h and with ≥ two risk factors for VTE were included. Patients receiving pharmacological thromboprophylaxis during their entire PICU stay were excluded. The primary outcome of the study was VTEs not related to the use of a CVC. Ultrasonography screening of the great veins was performed at PICU discharge. Seventy patients with median (interquartile range) 3 (2-4) risk factors for VTE were evaluated. Median age was 0.3 years (0.03-4.3) and median PICU length of stay 9 days (5-17). Regarding the primary outcome, no symptomatic VTEs occurred and no asymptomatic VTEs were found on ultrasonography screening, resulting in an incidence of VTEs not related to a vascular catheter of 0% (95% CI: 0-5.1%)., Conclusion: Our results indicate that VTEs not related to a vascular catheter are a rare event even in a selected group of severely ill small children considered to be at high risk of VTE., What Is Known: • Children in the PICU often have several risk factors for venous thromboembolism (VTE). • The incidence of VTE in PICU patients is highly uncertain, and there are no evidence-based guidelines regarding VTE prophylaxis., What Is New: • This study found an incidence of VTEs not related to a vascular catheter of 0% (95% CI: 0-5.1%). • This indicates that such VTE events are rare even in PICU patients with multiple risk factors for VTE., (© 2022. The Author(s).)

Monoclonal antibodies and antibody fragments are increasingly important classes of biotherapeutics. However, these products are both challenging and expensive to manufacture. New process analytical technologies used to monitor these products during their manufacture are of significant interest. Deep UV Raman spectroscopy promises to provide the required specificity and accuracy, however instruments, have historically been large and complex. In this paper, a new deep UV Raman instrument is described using a solid-state laser and a spatial heterodyne spectrometer. The instrument overcomes practical limitations of the technique and could readily be used for online measurement. A series of observations have been made of biopharmaceutical products, including immunoglobulin G and domain antibodies. Where high levels of both specificity and linearity when measuring samples of different concentration with a precision of better than 0.05 mg/mL has been demonstrated., (© 2022 IS-Instruments Ltd. Journal of Biophotonics published by Wiley-VCH GmbH.)

Purpose: We describe levels of cancer worry in the general population as measured with the Cancer Worry Scale (CWS) and investigate the association with colonoscopy screening intentions in three colorectal cancer risk scenarios., Methods: The data were sourced through a population-based survey. Respondents ( n = 943) completed an eight-item CWS and questions on colonoscopy screening interest at three hypothetical risk levels., Results: Respondents without a personal cancer history ( n = 853) scored 9.46 on the six-item CWS (mean, SD 2.72). Mean scores were significantly higher in women (9.91, SD 2.89) as compared to men (9.06, SD 2.49, p < 0.001). Linear regression showed higher cancer worry in women and those with children when controlling for education, age group, and country of birth. High cancer worry (six-item CWS mean >12) was identified in 25% of women and in 17% of men. Among those, 71% would attend a colonoscopy screening compared to 52% of those with low cancer worry ( p < 0.001, 5% CRC-risk)., Conclusions: The distribution of cancer worry in a general population sample showed higher mean scores in women, and levels overlapped with earlier findings in cancer-affected samples. Respondents with high cancer worry were more inclined to undergo a colonoscopy screening, and intention increased with higher levels of hypothetical risk.

Salinity normalization of total alkalinity (TA) and dissolved inorganic carbon (DIC) data is commonly used to account for conservative mixing processes when inferring net metabolic modification of seawater by coral reefs. Salinity (S), TA, and DIC can be accurately and precisely measured, but salinity normalization of TA (nTA) and DIC (nDIC) can generate considerable and unrecognized uncertainties in coral reef metabolic rate estimates. While salinity normalization errors apply to nTA, nDIC, and other ions of interest in coral reefs, here, we focus on nTA due to its application as a proxy for net coral reef calcification and the importance for reefs to maintain calcium carbonate production under environmental change. We used global datasets of coral reef TA, S, and modeled groundwater discharge to assess the effect of different volumetric ratios of multiple freshwater TA inputs (i.e., groundwater, river, surface runoff, and precipitation) on nTA. Coral reef freshwater endmember TA ranged from -2 up to 3032 μmol/kg in hypothetical reef locations with freshwater inputs dominated by riverine, surface runoff, or precipitation mixing with groundwater. The upper bound of freshwater TA in these scenarios can result in an uncertainty in reef TA of up to 90 μmol/kg per unit S normalization if the freshwater endmember is erroneously assumed to have 0 μmol/kg alkalinity. The uncertainty associated with S normalization can, under some circumstances, even shift the interpretation of whether reefs are net calcifying to net dissolving, or vice versa. Moreover, the choice of reference salinity for normalization implicitly makes assumptions about whether biogeochemical processes occur before or after mixing between different water masses, which can add uncertainties of ±1.4% nTA per unit S normalization. Additional considerations in identifying potential freshwater sources of TA and their relative volumetric impact on seawater are required to reduce uncertainties associated with S normalization of coral reef carbonate chemistry data in some environments. However, at a minimum, researchers should minimize the range of salinities over which the normalization is applied, precisely measure salinity, and normalize TA values to a carefully selected reference salinity that takes local factors into account., Competing Interests: The authors have declared that no competing interests exist.

The transition from preclinical biological drug development into clinical trials requires an efficient upscaling process. In this context, bispecific antibody drugs are particularly challenging due to their propensity to form aggregates and generally produce low titers. Here, the upscaling process for a tetravalent bispecific antibody expressed by a piggyBac transposon-mediated stable HEK293 cell pool has been evaluated. The project was performed as a case study at Testa Center, a non-GMP facility for scale-up testing of biologics in Sweden, and encompassed media adaptation strategies, fed-batch optimization and a novel antibody purification technology. The cell pool was adapted to different culture media for evaluation in terms of cell viability and titers compared to its original Expi293 Expression Medium. These parameters were assessed in both sequential stepwise adaption and direct media exchanges. By this, a more affordable medium was identified that did not require stepwise adaptation and with similar titers and viability as in the Expi293 Expression Medium. Fed-batch optimizations resulted in culture densities reaching up to 20 × 10 6 viable cells/mL with over 90 % viability 12 days post-inoculum, and antibody titers three times higher than corresponding batch cultures. By implementing a novel high-speed protein A fiber technology (Fibro PrismA) with a capture residence time of only 7.5 s, 8 L of supernatant could be purified in 4.5 h without compromising the purity, structural integrity and function of the bispecific antibody. Results from this study related to medium adaptation and design of fed-batch protocols will be highly beneficial during the forthcoming scale-up of this therapeutic antibody., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: Pediatric venous thromboembolic events are commonly associated with in situ central venous catheters. The risk for severe venous thromboembolism increases if a larger portion of the vessel lumen is occupied by the central venous catheter. A functioning vascular catheter is required when the continuous renal replacement therapy is used in critically ill children. Due to the high blood flow required for continuous renal replacement therapy, the external diameter of the catheter needs to be larger than a conventional central venous catheter used for venous access, potentially increasing the risk of venous thromboembolism. However, children on continuous renal replacement therapy often receive systemic anticoagulation to prevent filter clotting, possibly also preventing venous thromboembolism. The frequency of catheter-related venous thromboembolic events in this setting has not been described. Our main objective was to determine the prevalence of catheter-related venous thromboembolism in pediatric continuous renal replacement therapy., Design: Retrospective cohort study., Setting: Tertiary multidisciplinary academic pediatric hospital., Patients: Patients 0-18 years old with a vascular catheter used for continuous renal replacement therapy., Interventions: None., Measurements and Main Results: In our series of 80 patients, we used 105 vascular catheters. The median age of the patients was 10 months and PICU mortality rate was 21%. Venous thromboembolic events were considered to be catheter related if located in the same vein as the vascular catheter and radiologically verified. Six (5.7%) catheter-related venous thromboembolic events were found. The clinically relevant complications of venous thromboembolism included superior vena cava syndrome and catheter dysfunction. In one patient, severe and life-threatening pulmonary embolism occurred. In comparison with patients without venous thromboembolism, venous thromboembolic events were associated with lower body weight (p = 0.03) and longer durations of continuous renal replacement therapy (p < 0.01), mechanical ventilation (p = 0.03), and PICU stay (p < 0.01). Five out of six venous thromboembolisms appeared in neonates., Conclusions: Catheter-related venous thromboembolism is a clinically relevant complication of pediatric continuous renal replacement therapy, with a prevalence of 5.7% in our cohort. Clinicians involved in pediatric continuous renal replacement therapy need to be vigilant for symptoms of venous thromboembolisms and initiate appropriate treatment as soon as possible., Competing Interests: Dr. Szeps disclosed that this study was funded through institutional funds only. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Transfusions should be given for medical indications and based on the clinical context for the individual patient. Clinicians should follow the most current existing clinical guidelines. The neonatal hemostatic system differs significantly from that of children and adults. Still, healthy neonates have a balanced hemostatic system. Since the level of hemoglobin is critical to tissue oxygenation, it is important in the rapidly developing neonate. For preterm neonates, different red blood cell transfusion thresholds should be used based on postnatal age and illness severity. Most hemodynamically stable pediatric intensive care patients with a hemoglobin >70 g/L do not require transfusion. Pediatric massive transfusion protocols should exist in pediatric hospitals. At Karolinska University Hospital, red blood cells, fresh frozen plasma and platelets are transfused in a ratio of 20:20:10 mL/kg to children <50 kg. In liver disease, transfusions can lead to increased bleeding.

The hydrodynamics within small boreal lakes have rarely been studied, yet knowing whether turbulence at the air-water interface and in the water column scales with metrics developed elsewhere is essential for computing metabolism and fluxes of climate-forcing trace gases. We instrumented a humic, 4.7 ha, boreal lake with two meteorological stations, three thermistor arrays, an infrared (IR) camera to quantify surface divergence, obtained turbulence as dissipation rate of turbulent kinetic energy ( ε ) using an acoustic Doppler velocimeter and a temperature-gradient microstructure profiler, and conducted chamber measurements for short periods to obtain fluxes and gas transfer velocities ( k ). Near-surface ε varied from 10 -8 to 10 -6 m 2 s -3 for the 0-4 m s -1 winds and followed predictions from Monin-Obukhov similarity theory. The coefficient of eddy diffusivity in the mixed layer was up to 10 -3 m 2 s -1 on the windiest afternoons, an order of magnitude less other afternoons, and near molecular at deeper depths. The upper thermocline upwelled when Lake numbers ( L N ) dropped below four facilitating vertical and horizontal exchange. k computed from a surface renewal model using ε agreed with values from chambers and surface divergence and increased linearly with wind speed. Diurnal thermoclines formed on sunny days when winds were < 3 m s -1 , a condition that can lead to elevated near-surface ε and k . Results extend scaling approaches developed in the laboratory and for larger water bodies, illustrate turbulence and k are greater than expected in small wind-sheltered lakes, and provide new equations to quantify fluxes., Competing Interests: None declared., (© 2020 The Authors. Limnology and Oceanography published by Wiley Periodicals LLC on behalf of Association for the Sciences of Limnology and Oceanography.)

The North Atlantic Oscillation (NAO) has been hypothesized to drive interannual variability in Bermudan coral extension rates and reef-scale calcification through the provisioning of nutritional pulses associated with negative NAO winters. However, the direct influence of the NAO on Bermudan coral calcification rates remains to be determined and may vary between species and reef sites owing to implicit differences in coral life history strategies and environmental gradients across the Bermuda reef platform. In this study, we investigated the connection between negative NAO winters and Bermudan Diploria labyrinthiformis, Pseudodiploria strigosa, and Orbicella franksi coral calcification rates across rim reef, lagoon, and nearshore reef sites. Linear mixed effects modeling detected an inverse correlation between D. labyrinthiformis calcification rates and the winter NAO index, with higher rates associated with increasingly negative NAO winters. Conversely, there were no detectable correlations between P. strigosa or O. franksi calcification rates and the winter NAO index suggesting that coral calcification responses associated with negative NAO winters could be species-specific. The correlation between coral calcification rates and winter NAO index was significantly more negative at the outer rim of the reef (Hog Reef) compared to a nearshore reef site (Whalebone Bay), possibly indicating differential influence of the NAO as a function of the distance from the reef edge. Furthermore, a negative calcification anomaly was observed in 100% of D. labyrinthiformis cores in association with the 1988 coral bleaching event with a subsequent positive calcification anomaly in 1989 indicating a post-bleaching recovery in calcification rates. These results highlight the importance of assessing variable interannual coral calcification responses between species and across inshore-offshore gradients to interannual atmospheric modes such as the NAO, thermal stress events, and potential interactions between ocean warming and availability of coral nutrition to improve projections for future coral calcification rates under climate change., Competing Interests: The authors have declared that no competing interests exist.

Background: Targeted surveillance of at-risk individuals in families with increased risk of hereditary cancer is an effective prevention strategy if relatives are identified, informed and enrolled in screening programs. Despite the potential benefits, many eligible at-risk relatives remain uninformed of their cancer risk. This study describes the general public's opinion on disclosure of hereditary colorectal cancer (CRC) risk information, as well as preferences on the source and the mode of information., Methods: A random sample of the general public was assessed through a Swedish citizen web-panel. Respondents were presented with scenarios of being an at-risk relative in a family that had an estimated increased hereditary risk of CRC; either 10% (moderate) or 70% (high) lifetime risk. A colonoscopy was presented as a preventive measure. Results were analysed to identify significant differences between groups using the Pearson's chi-square (χ 2 ) test., Results: Of 1800 invited participants, 977 completed the survey (54%). In the moderate and high-risk scenarios, 89.2 and 90.6% respectively, would like to receive information about a potential hereditary risk of CRC (χ2, p  = .755). The desire to be informed was higher among women (91.5%) than men (87.0%, χ2, p  = .044). No significant differences were found when comparing different age groups, educational levels, place of residence and having children or not. The preferred source of risk information was a healthcare professional in both moderate and high-risk scenarios (80.1 and 75.5%). However, 18.1 and 20.1% respectively would prefer to be informed by a family member. Assuming that healthcare professionals disclosed the information, the favoured mode of information was letter and phone (38.4 and 33.2%)., Conclusions: In this study a majority of respondents wanted to be informed about a potential hereditary risk of CRC and preferred healthcare professionals to communicate this information. The two presented levels of CRC lifetime risk did not significantly affect the interest in being informed. Our data offer insights into the needs and preferences of the Swedish population, providing a rationale for developing complementary healthcare-assisted communication pathways to realise the full potential of targeted prevention of hereditary CRC., Competing Interests: Competing interestsThe author(s) declare that they have no competing interest., (© The Author(s) 2020.)

Background: Venous thrombosis (VT) in children is often associated with a central venous catheter (CVC). We aimed to determine the incidence of VT associated with percutaneous non-tunnelled CVCs in a general paediatric population, and to identify risk factors for VT in this cohort., Methods: Observational, prospective study enrolling consecutive patients at a tertiary multi-disciplinary paediatric hospital. A total of 211 percutaneous, non-tunnelled CVCs were analysed. Data regarding potential risk factors for CVC-related VT were collected. Compression ultrasonography with colour Doppler was used to diagnose VT., Results: Overall, 30.3% of children developed CVC-related VT, with an incidence rate of 29.6 (confidence interval, 22.5-36.9) cases/1000 CVC days. Upper body CVC location, multiple lumen CVCs, and male gender were independent risk factors for VT in multivariate analysis. All upper body VTs were in the internal jugular vein (IJV). The occurrence of CVC-related VT did not affect length of paediatric ICU or hospital stay. In patients with VT, femoral CVCs, young age, paediatric ICU admission, and a ratio of CVC/vein diameter >0.33 were associated with VT being symptomatic, occlusive, or both. IJV VT was often asymptomatic and non-occlusive., Conclusions: Paediatric non-tunnelled CVCs are frequently complicated by VT. Avoiding IJV CVCs and multiple lumen catheters could potentially reduce the overall risk of VT. However, IJV VT was more likely to be smaller and asymptomatic compared with femoral vein VT. More data are needed on the risk of complications from smaller, asymptomatic VT compared with the group of VT with symptoms or vein occlusion. Femoral vein CVCs and CVC/vein diameter >0.33 could be modifiable risk factors for VT with larger thrombotic mass., Clinical Trial Registration: ACTRN12615000442505., (Copyright © 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Patients with multiple organ failure (MOF) often receive large amounts of resuscitation fluid, making them at high risk of fluid overload (FO). Our main objective was to investigate if the ability to achieve a negative fluid balance during the first 3 continuous renal replacement therapy (CRRT) days was associated with mortality in children with MOF., Methods: Retrospective cohort study in a tertiary multidisciplinary academic paediatric hospital. The study included 63 patients (age 0-18 years) with 3 or more failing organs receiving CRRT due to acute kidney injury and/or fluid overload., Results: The median age was 4 months, and PICU mortality was 29%. Survivors had significantly lower degree of FO at CRRT initiation, (median 15% (Interquartile range 9-22)) than non-survivors (24% (17%-37%), P = 0.002). On PICU admission, PIM-3 score was significantly higher in non-survivors (P = 0.01), but at CRRT initiation there was no difference in PELOD-2 score (P = 0.98). Mortality in patients achieving a cumulative net negative fluid balance during the first 3 days after CRRT initiation was 12%, compared to 86% in those not achieving this (P < 0.0001). In multivariate analysis, the inability to achieve a net negative fluid balance during 3 days after CRRT initiation (P < 0.0001) and FO >20% at CRRT initiation (P = 0.0019) remained associated with mortality., Conclusion: Our results suggest that early fluid removal is associated with improved patient outcome in critically ill children receiving CRRT, and that prompt measures should be taken to prevent fluid overload in critical illness. These results need to be verified in further, prospective studies., (© 2019 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

In vast areas of the ocean, the scarcity of iron controls the growth and productivity of phytoplankton. Although most dissolved iron in the marine environment is complexed with organic molecules, picomolar amounts of labile inorganic iron species (labile iron) are maintained within the euphotic zone and serve as an important source of iron for eukaryotic phytoplankton and particularly for diatoms. Genome-enabled studies of labile iron utilization by diatoms have previously revealed novel iron-responsive transcripts, including the ferric iron-concentrating protein ISIP2A, but the mechanism behind the acquisition of picomolar labile iron remains unknown. Here we show that ISIP2A is a phytotransferrin that independently and convergently evolved carbonate ion-coordinated ferric iron binding. Deletion of ISIP2A disrupts high-affinity iron uptake in the diatom Phaeodactylum tricornutum, and uptake is restored by complementation with human transferrin. ISIP2A is internalized by endocytosis, and manipulation of the seawater carbonic acid system reveals a second-order dependence on the concentrations of labile iron and carbonate ions. In P. tricornutum, the synergistic interaction of labile iron and carbonate ions occurs at environmentally relevant concentrations, revealing that carbonate availability co-limits iron uptake. Phytotransferrin sequences have a broad taxonomic distribution and are abundant in marine environmental genomic datasets, suggesting that acidification-driven declines in the concentration of seawater carbonate ions will have a negative effect on this globally important eukaryotic iron acquisition mechanism.

Ocean acidification refers to the lowering of the ocean's pH due to the uptake of anthropogenic CO 2 from the atmosphere. Coral reef calcification is expected to decrease as the oceans become more acidic. Dissolving calcium carbonate (CaCO 3 ) sands could greatly exacerbate reef loss associated with reduced calcification but is presently poorly constrained. Here we show that CaCO 3 dissolution in reef sediments across five globally distributed sites is negatively correlated with the aragonite saturation state (Ω ar ) of overlying seawater and that CaCO 3 sediment dissolution is 10-fold more sensitive to ocean acidification than coral calcification. Consequently, reef sediments globally will transition from net precipitation to net dissolution when seawater Ω ar reaches 2.92 ± 0.16 (expected circa 2050 CE). Notably, some reefs are already experiencing net sediment dissolution., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Worldwide, coral reef ecosystems are experiencing increasing pressure from a variety of anthropogenic perturbations including ocean warming and acidification, increased sedimentation, eutrophication, and overfishing, which could shift reefs to a condition of net calcium carbonate (CaCO3) dissolution and erosion. Herein, we determine the net calcification potential and the relative balance of net organic carbon metabolism (net community production; NCP) and net inorganic carbon metabolism (net community calcification; NCC) within 23 coral reef locations across the globe. In light of these results, we consider the suitability of using these two metrics developed from total alkalinity (TA) and dissolved inorganic carbon (DIC) measurements collected on different spatiotemporal scales to monitor coral reef biogeochemistry under anthropogenic change. All reefs in this study were net calcifying for the majority of observations as inferred from alkalinity depletion relative to offshore, although occasional observations of net dissolution occurred at most locations. However, reefs with lower net calcification potential (i.e., lower TA depletion) could shift towards net dissolution sooner than reefs with a higher potential. The percent influence of organic carbon fluxes on total changes in dissolved inorganic carbon (DIC) (i.e., NCP compared to the sum of NCP and NCC) ranged from 32% to 88% and reflected inherent biogeochemical differences between reefs. Reefs with the largest relative percentage of NCP experienced the largest variability in seawater pH for a given change in DIC, which is directly related to the reefs ability to elevate or suppress local pH relative to the open ocean. This work highlights the value of measuring coral reef carbonate chemistry when evaluating their susceptibility to ongoing global environmental change and offers a baseline from which to guide future conservation efforts aimed at preserving these valuable ecosystems.

Modern reef-building corals sustain a wide range of ecosystem services because of their ability to build calcium carbonate reef systems. The influence of environmental variables on coral calcification rates has been extensively studied, but our understanding of their relative importance is limited by the absence of in situ observations and the ability to decouple the interactions between different properties. We show that temperature is the primary driver of coral colony ( Porites astreoides and Diploria labyrinthiformis ) and reef-scale calcification rates over a 2-year monitoring period from the Bermuda coral reef. On the basis of multimodel climate simulations (Coupled Model Intercomparison Project Phase 5) and assuming sufficient coral nutrition, our results suggest that P. astreoides and D. labyrinthiformis coral calcification rates in Bermuda could increase throughout the 21st century as a result of gradual warming predicted under a minimum CO 2 emissions pathway [representative concentration pathway (RCP) 2.6] with positive 21st-century calcification rates potentially maintained under a reduced CO 2 emissions pathway (RCP 4.5). These results highlight the potential benefits of rapid reductions in global anthropogenic CO 2 emissions for 21st-century Bermuda coral reefs and the ecosystem services they provide.

Oceanic uptake of anthropogenic carbon dioxide (CO2) has acidified open-ocean surface waters by 0.1 pH units since preindustrial times. Despite unequivocal evidence of ocean acidification (OA) via open-ocean measurements for the past several decades, it has yet to be documented in near-shore and coral reef environments. A lack of long-term measurements from these environments restricts our understanding of the natural variability and controls of seawater CO2-carbonate chemistry and biogeochemistry, which is essential to make accurate predictions on the effects of future OA on coral reefs. Here, in a 5-y study of the Bermuda coral reef, we show evidence that variations in reef biogeochemical processes drive interannual changes in seawater pH and Ωaragonite that are partly controlled by offshore processes. Rapid acidification events driven by shifts toward increasing net calcification and net heterotrophy were observed during the summers of 2010 and 2011, with the frequency and extent of such events corresponding to increased offshore productivity. These events also coincided with a negative winter North Atlantic Oscillation (NAO) index, which historically has been associated with extensive offshore mixing and greater primary productivity at the Bermuda Atlantic Time-series Study (BATS) site. Our results reveal that coral reefs undergo natural interannual events of rapid acidification due to shifts in reef biogeochemical processes that may be linked to offshore productivity and ultimately controlled by larger-scale climatic and oceanographic processes.

Understanding bacterioplankton community dynamics in coastal hypoxic environments is relevant to global biogeochemistry because coastal hypoxia is increasing worldwide. The temporal dynamics of bacterioplankton communities were analysed throughout the illuminated water column of Devil's Hole, Bermuda during the 6-week annual transition from a strongly stratified water column with suboxic and high-pCO2 bottom waters to a fully mixed and ventilated state during 2008. A suite of culture-independent methods provided a quantitative spatiotemporal characterization of bacterioplankton community changes, including both direct counts and rRNA gene sequencing. During stratification, the surface waters were dominated by the SAR11 clade of Alphaproteobacteria and the cyanobacterium Synechococcus. In the suboxic bottom waters, cells from the order Chlorobiales prevailed, with gene sequences indicating members of the genera Chlorobium and Prosthecochloris--anoxygenic photoautotrophs that utilize sulfide as a source of electrons for photosynthesis. Transitional zones of hypoxia also exhibited elevated levels of methane- and sulfur-oxidizing bacteria relative to the overlying waters. The abundance of both Thaumarcheota and Euryarcheota were elevated in the suboxic bottom waters (> 10(9) cells l(-1)). Following convective mixing, the entire water column returned to a community typical of oxygenated waters, with Euryarcheota only averaging 5% of cells, and Chlorobiales and Thaumarcheota absent., (© 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.)

The persistence of carbonate structures on coral reefs is essential in providing habitats for a large number of species and maintaining the extraordinary biodiversity associated with these ecosystems. As a consequence of ocean acidification (OA), the ability of marine calcifiers to produce calcium carbonate (CaCO(3)) and their rate of CaCO(3) production could decrease while rates of bioerosion and CaCO(3) dissolution could increase, resulting in a transition from a condition of net accretion to one of net erosion. This would have negative consequences for the role and function of coral reefs and the eco-services they provide to dependent human communities. In this article, we review estimates of bioerosion, CaCO(3) dissolution, and net ecosystem calcification (NEC) and how these processes will change in response to OA. Furthermore, we critically evaluate the observed relationships between NEC and seawater aragonite saturation state (Ω(a)). Finally, we propose that standardized NEC rates combined with observed changes in the ratios of dissolved inorganic carbon to total alkalinity owing to net reef metabolism may provide a biogeochemical tool to monitor the effects of OA in coral reef environments.

Meta-analysis of experimental results has been interpreted to imply that the calcification response of organisms depositing high Mg-calcite is more resilient to ocean acidification than organisms depositing aragonite/calcite. This conclusion might be biased by inadequate recognition and categorisation of high Mg-calcite according to mineral solubility., (© 2011 Blackwell Publishing Ltd/CNRS.)

Ocean acidification produced by dissolution of anthropogenic carbon dioxide (CO(2)) emissions in seawater has profound consequences for marine ecology and biogeochemistry. The oceans have absorbed one-third of CO(2) emissions over the past two centuries, altering ocean chemistry, reducing seawater pH, and affecting marine animals and phytoplankton in multiple ways. Microbially mediated ocean biogeochemical processes will be pivotal in determining how the earth system responds to global environmental change; however, how they may be altered by ocean acidification is largely unknown. We show here that microbial nitrification rates decreased in every instance when pH was experimentally reduced (by 0.05-0.14) at multiple locations in the Atlantic and Pacific Oceans. Nitrification is a central process in the nitrogen cycle that produces both the greenhouse gas nitrous oxide and oxidized forms of nitrogen used by phytoplankton and other microorganisms in the sea; at the Bermuda Atlantic Time Series and Hawaii Ocean Time-series sites, experimental acidification decreased ammonia oxidation rates by 38% and 36%. Ammonia oxidation rates were also strongly and inversely correlated with pH along a gradient produced in the oligotrophic Sargasso Sea (r(2) = 0.87, P < 0.05). Across all experiments, rates declined by 8-38% in low pH treatments, and the greatest absolute decrease occurred where rates were highest off the California coast. Collectively our results suggest that ocean acidification could reduce nitrification rates by 3-44% within the next few decades, affecting oceanic nitrous oxide production, reducing supplies of oxidized nitrogen in the upper layers of the ocean, and fundamentally altering nitrogen cycling in the sea.

Background: Endothelin-1 is a potent endogenous vasoconstrictor that contributes to renal microcirculatory impairment during endotoxemia and sepsis. Here we investigated if the renal circulatory and metabolic effects of endothelin during endotoxemia are mediated through activation of endothelin-A receptors., Methods and Findings: A randomized experimental study was performed with anesthetized and mechanically ventilated pigs subjected to Escherichia coli endotoxin infusion for five hours. After two hours the animals were treated with the selective endothelin receptor type A antagonist TBC 3711 (2 mg⋅kg(-1), n = 8) or served as endotoxin-treated controls (n = 8). Renal artery blood flow, diuresis and creatinine clearance decreased in response to endotoxemia. Perfusion in the cortex, as measured by laser doppler flowmetry, was reduced in both groups, but TBC 3711 attenuated the decrease in the medulla (p = 0.002). Compared to control, TBC 3711 reduced renal oxygen extraction as well as cortical and medullary lactate/pyruvate ratios (p<0.05) measured by microdialysis. Furthermore, TBC 3711 attenuated the decline in renal cortical interstitial glucose levels (p = 0.02) and increased medullary pyruvate levels (p = 0.03). Decreased creatinine clearance and oliguria were present in both groups without any significant difference., Conclusions: These results suggest that endothelin released during endotoxemia acts via endothelin A receptors to impair renal medullary blood flow causing ischemia. Reduced renal oxygen extraction and cortical levels of lactate by TBC 3711, without effects on cortical blood flow, further suggest additional metabolic effects of endothelin type A receptor activation in this model of endotoxin induced acute kidney injury.

Beneficial anti-inflammatory properties have been ascribed to volatile anesthetics in septic conditions, but no studies have compared anesthesia to the conscious state in a large-animal model. The aim of this study was to investigate the effect of isoflurane anesthesia on cardiovascular and respiratory function, leukocyte activation, and lung damage in a model of endotoxemia in sheep. Conscious (n = 6) and anesthetized (n = 6) sheep were made endotoxemic by continuous infusion of LPS for 48 h. Central hemodynamics were monitored continuously, and blood samples were collected regularly. Activation of leukocytes was assessed by surface expression of CD11b and plasma myeloperoxidase concentration. Lung damage was determined by electron microscopy, cell count in bronchoalveolar lavage fluid, and analysis of lung vascular permeability. Four additional animals (two conscious and two anesthetized) went through the same protocol but did not receive LPS. LPS infusion induced a hyperdynamic sepsis. The drop in total peripheral resistance was compensated by an increase in heart rate and cardiac output in the conscious group, whereas anesthetized sheep failed to compensate in this way. Endotoxemic isoflurane-anesthetized sheep also showed signs of aggravated lung edema formation and tissue damage together with enhanced neutrophil activation and lung tissue accumulation. Our data suggest that isoflurane in conjunction with mechanical ventilation blunts cardiovascular compensatory mechanisms in sepsis and enhances leukocyte activation, which may contribute to lung edema formation and tissue damage.

The oceans play a key role in climate regulation especially in part buffering (neutralising) the effects of increasing levels of greenhouse gases in the atmosphere and rising global temperatures. This chapter examines how the regulatory processes performed by the oceans alter as a response to climate change and assesses the extent to which positive feedbacks from the ocean may exacerbate climate change. There is clear evidence for rapid change in the oceans. As the main heat store for the world there has been an accelerating change in sea temperatures over the last few decades, which has contributed to rising sea-level. The oceans are also the main store of carbon dioxide (CO2), and are estimated to have taken up approximately 40% of anthropogenic-sourced CO2 from the atmosphere since the beginning of the industrial revolution. A proportion of the carbon uptake is exported via the four ocean 'carbon pumps' (Solubility, Biological, Continental Shelf and Carbonate Counter) to the deep ocean reservoir. Increases in sea temperature and changing planktonic systems and ocean currents may lead to a reduction in the uptake of CO2 by the ocean; some evidence suggests a suppression of parts of the marine carbon sink is already underway. While the oceans have buffered climate change through the uptake of CO2 produced by fossil fuel burning this has already had an impact on ocean chemistry through ocean acidification and will continue to do so. Feedbacks to climate change from acidification may result from expected impacts on marine organisms (especially corals and calcareous plankton), ecosystems and biogeochemical cycles. The polar regions of the world are showing the most rapid responses to climate change. As a result of a strong ice-ocean influence, small changes in temperature, salinity and ice cover may trigger large and sudden changes in regional climate with potential downstream feedbacks to the climate of the rest of the world. A warming Arctic Ocean may lead to further releases of the potent greenhouse gas methane from hydrates and permafrost. The Southern Ocean plays a critical role in driving, modifying and regulating global climate change via the carbon cycle and through its impact on adjacent Antarctica. The Antarctic Peninsula has shown some of the most rapid rises in atmospheric and oceanic temperature in the world, with an associated retreat of the majority of glaciers. Parts of the West Antarctic ice sheet are deflating rapidly, very likely due to a change in the flux of oceanic heat to the undersides of the floating ice shelves. The final section on modelling feedbacks from the ocean to climate change identifies limitations and priorities for model development and associated observations. Considering the importance of the oceans to climate change and our limited understanding of climate-related ocean processes, our ability to measure the changes that are taking place are conspicuously inadequate. The chapter highlights the need for a comprehensive, adequately funded and globally extensive ocean observing system to be implemented and sustained as a high priority. Unless feedbacks from the oceans to climate change are adequately included in climate change models, it is possible that the mitigation actions needed to stabilise CO2 and limit temperature rise over the next century will be underestimated.

Background: Microcirculatory dysfunction is a common feature of sepsis. The potent vasoconstrictor endothelin (ET) is released in sepsis and endotoxemia, potentially contributing to sepsis-induced microcirculatory failure. In this study we tested the hypothesis that mixed ET receptor antagonism with tezosentan would improve splanchnic microcirculatory blood flow in acute porcine endotoxemia., Materials and Methods: Sixteen anesthetized and mechanically ventilated pigs received an infusion of endotoxin for 300 min. After 120 min eight pigs received a bolus dose of tezosentan 1 mg/kg followed by an infusion of tezosentan of 1 mg/kg/h throughout the experiment. Eight pigs served as endotoxin controls. Laser Doppler flowmetry was used to measure microcirculatory blood flow in the liver and in the ileal and colon mucosa. PCO(2) in the ileal mucosa was measured by air tonometry and portal vein flow by an ultrasonic flow probe., Results: Endotoxin administration induced a state of shock with impaired splanchnic microcirculatory blood flow. Microcirculation in the mucosa of the colon and ileum and mucosal-arterial PCO(2) gap were improved by tezosentan. Portal vein flow was increased, but hepatic microcirculatory blood flow was not significantly improved. Tezosentan preserved cardiac index and decreased pulmonary capillary wedge pressure compared to controls, without causing any differences in the heart rate or mean arterial blood pressure response. Tezosentan also distinctly improved pH and arterial lactate values., Conclusions: The findings of this study indicate that ET is involved in the microcirculatory dysfunction seen in the ileal and colon mucosa in early endotoxemia. Moreover, this detrimental effect was counteracted by i.v. administration of the mixed ET receptor antagonist tezosentan.