Ex vivo normothermic perfusion (EVNP) is a novel method of preservation that restores circulation and allows an organ to regain function prior to transplantation. The aim of this study was to assess ...the effects of EVNP in kidneys from marginal donors. Eighteen kidneys from extended criteria donors (ECD) underwent a period of EVNP immediately before transplantation. Kidneys were perfused with a plasma free red‐cell based solution at a mean temperature of 34.6°C. The outcome of these kidneys was compared to a control group of 47 ECD kidneys that underwent static cold storage (CS). The mean donor age was 61 ± 1 years in the EVNP and 62 ± 6 years in the CS group (p = 0.520). EVNP kidneys were perfused for an average of 63 ± 16 min and all were transplanted successfully. The delayed graft function rate (DGF), defined as the requirement for dialysis within the first 7 days was 1/18 patients (5.6%) in the EVNP group versus 17/47 (36.2%) in the CS group (p = 0.014). There was no difference in graft or patient survival at 12 months (p = 0.510, 1.000). This first series of EVNP in renal transplantation demonstrates that this technique is both feasible and safe. Our preliminary data suggests that EVNP offers promise as a new technique of kidney preservation.
This study reports early promising results from a pilot experience with ex vivo normothermic kidney perfusion using extended criteria donor kidneys.
In the sea‐ice‐impacted Southern Ocean, the spring sea‐ice melt and its impact on physical processes set the rate of surface water mass modification. These modified waters will eventually subduct ...near the polar front and enter the global overturning circulation. Submesoscale processes modulate the stratification of the mixed layer (ML) and ML properties. Sparse observations in polar regions mean that the role of submesoscale motions in the exchange of properties across the base of the ML is not well understood. The goal of this study is to determine the interplay between sea‐ice melt, surface boundary layer forcing, and submesoscale flows in setting properties of the surface ML in the Antarctic marginal ice zone. High‐resolution observations suggest that fine‐scale lateral fronts arise from either/both mesoscale and submesoscale stirring of sea‐ice meltwater anomalies. The strong salinity‐driven stratification at the base of the ML confines these fronts to the upper ocean, limiting submesoscale vertical fluxes across the ML base. This strong stratification prevents the local subduction of modified waters by submesoscale flows, suggesting that the subduction site that links to the global overturning circulation does not correspond with the location of sea‐ice melt. However, surface‐enhanced fronts increase the potential for Ekman‐driven cross‐frontal flow to modulate the stability of the ML and ML properties. The parameterization of submesoscale processes in coupled‐climate models, particularly those contributing to the Ekman buoyancy flux, may improve the representation of ML heat and freshwater transport in the ice‐impacted Southern Ocean during summer.
Plain Language Summary
Sea‐ice melt around Antarctica is an annual event in which the state of the surface ocean is transformed, during which over 15 trillion liters of freshwater enter the upper ocean. This fresh layer separates the upper ocean from the deep ocean and suppresses the exchange of heat and gases—like carbon dioxide—between the deep ocean and the atmosphere, with important implications for the climate system. Using state‐of‐the‐art autonomous underwater gliders, we observed key physical properties of the surface ocean following the melt of sea‐ice. The presence of fine‐scale fronts (sharp changes in density), of less than 10 km at horizontal scales, revealed that sea‐ice melt not only stabilizes the upper ocean, but also provides additional energy for small eddies and filaments to form. While the eddies are unable to extend deeper than the fresher surface layer, they enhance the ocean response to winds. These findings may contribute to the improvement of global climate models and our understanding of how the ocean will react to changes in sea‐ice under a warmer climate.
Key Points
Sea‐ice meltwater controls the buoyancy of the mixed layer during early summer
Mixed layer eddies grow from mesoscale meltwater lateral gradients but are confined to the surface boundary layer
Observations suggest that mixed layer variability at submesoscales is dominated by wind‐front interactions
The Antarctic Marginal Ice Zone (MIZ) accounts for 15% of the Southern Ocean's primary production (PP), but limited data has hindered understanding of its variability and connection to carbon export. ...Using a combination of gliders, biogeochemical Argo floats and satellite observations in the northeast Weddell Sea, we show that years with more sea‐ice formation over winter are followed by more intense phytoplankton blooms (∼15% greater daily PP) and export to 100 m (∼50% higher daily carbon export) the following summer. However, the carbon export beyond the deepest winter mixed layer did not vary in proportion to PP, suggesting different drivers of carbon export at depth compared to surface waters. Furthermore, across the entire MIZ, the response of blooms to sea‐ice volume was spatially variable, indicating the need to consider spatial heterogeneity in the response of the biological carbon pump to future sea‐ice changes.
Plain Language Summary
Algae in the ocean surface take up carbon dioxide from the atmosphere through photosynthesis and transfer it to the deep ocean when they die and sink. This process is key to maintaining a habitable planet and is known as the biological carbon pump (BCP). The seasonally ice‐covered ocean around Antarctica is one of the most active areas for algal growth, but also a region of rapid climate change. Because of the difficulty in taking measurements in this remote region, the physical and biological processes that control the growth and sinking of algae and its response to changing sea‐ice remain uncertain. In this study, we use a combination of satellites and autonomous robots to elucidate the role of sea‐ice variability on the BCP. We find that sea‐ice impacts algal growth by its influence on both the light and nutrient conditions needed for photosynthesis. Predicting the amount of algae that subsequently sinks to depth as carbon flux, although influenced by sea‐ice conditions, is more complex and linked to the greater marine ecosystem. Evidence suggests that the species of algae, zooplankton grazing, and the rate at which dead algae breaks down and sinks are important and should be a focus point for further research.
Key Points
High‐resolution in‐situ observations are used to characterize multi‐year phytoplankton bloom phenology and amplitude in the Antarctic Marginal Ice Zone
Years with greater sea‐ice volume drive deeper mixing that tend to support higher magnitude blooms in the northeast Weddell Sea
Carbon export efficiency is affected by bloom magnitude, community composition and water column stratification
Genome-wide association studies (GWAS) have identified loci reproducibly associated with pulmonary diseases; however, the molecular mechanism underlying these associations are largely unknown. The ...objectives of this study were to discover genetic variants affecting gene expression in human lung tissue, to refine susceptibility loci for asthma identified in GWAS studies, and to use the genetics of gene expression and network analyses to find key molecular drivers of asthma. We performed a genome-wide search for expression quantitative trait loci (eQTL) in 1,111 human lung samples. The lung eQTL dataset was then used to inform asthma genetic studies reported in the literature. The top ranked lung eQTLs were integrated with the GWAS on asthma reported by the GABRIEL consortium to generate a Bayesian gene expression network for discovery of novel molecular pathways underpinning asthma. We detected 17,178 cis- and 593 trans- lung eQTLs, which can be used to explore the functional consequences of loci associated with lung diseases and traits. Some strong eQTLs are also asthma susceptibility loci. For example, rs3859192 on chr17q21 is robustly associated with the mRNA levels of GSDMA (P = 3.55 × 10(-151)). The genetic-gene expression network identified the SOCS3 pathway as one of the key drivers of asthma. The eQTLs and gene networks identified in this study are powerful tools for elucidating the causal mechanisms underlying pulmonary disease. This data resource offers much-needed support to pinpoint the causal genes and characterize the molecular function of gene variants associated with lung diseases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Dissolved iron (DFe) plays an immeasurable role in shaping the biogeochemical processes of the open‐ocean Southern Ocean. However, due to observational constraints iron supply pathways remain poorly ...understood. Using an idealized eddy‐resolving physical‐biogeochemical model representing a turbulent sector of the Southern Ocean with seasonal buoyancy forcing and zonal winds overlaid by storms, we quantify the importance of a range of subsurface and surface iron supply mechanisms. The main physical supply pathways to the surface layer are via eddy advection and winter convective mixing in equal proportions. The associated subsurface loss of DFe is restocked via net remineralization (75%) and eddy advection (25%). Summer storms resulted in weak DFe supplies relative to the seasonal supplies (<7.6%). However, in situations of deep summer mixed layers and when interacting with underlying ocean fronts, summer storms resulted in enhanced diffusive and advective DFe supplies and raised summer primary production by 20% for several days.
Plain Language Summary
The surface of the Southern Ocean is iron depleted, which strongly limits the amount of phytoplankton growth that can occur. Every year, deep mixing in winter moves large quantities of iron from a subsurface underutilized iron reservoir to the surface alleviating the iron limitation. Once there is sufficient light in spring, phytoplankton consume this iron supply leaving the summer months iron depleted. How exactly phytoplankton are supported through the summer when iron limitations are strong remains under question. This study uses a numerical model to simulate the seasonal and intraseasonal iron supply pathways. We show that physical supplies via advection by eddies and winter mixing drive surface seasonal supplies in equal proportions. During summer, storms supply iron via intermittent mixing and thus increase primary production, particularly over regions of strong ocean fronts.
Key Points
Eddy advection and winter mixing support annual surface iron supplies in equal proportion in an eddy‐resolving model
Eddy advection contributes 25% to restocking subsurface iron reservoir in addition to 75% by local recycling
Storms are the most efficient in increasing iron supplies in early summer and over ocean fronts
Laparoscopic surgery reduces pain after donor nephrectomy; however, most patients still require a significant amount of postoperative parenteral opiate analgesia. Therefore, there is a need to ...investigate techniques that might further reduce postoperative pain. This study assessed the safety and efficacy of using a transversus abdominis plane (TAP) block in a randomized, double-blind, placebo-controlled trial.
Forty-six patients were analyzed in the trial and were randomized to undergo the TAP block procedure with either bupivacaine (n=24) or saline placebo (Control n=22) injected into the muscle plane. Prefilled syringes were dispensed with the group allocation concealed to maintain blinding. After surgery, the amount of morphine, level of pain, and measures of recovery were recorded.
The amount of morphine used 6 hr after surgery was significantly lower in patients receiving TAP block with bupivacaine compared with the control (presented as mean SD, 12.4 8.4 vs. 21.2 14.0 mg; P=0.015). However, the total amount of morphine used was similar in both groups 45.6 31.4 vs. 52.7 28.8 mg; P=0.771. Patients in the bupivacaine group experienced significantly less pain on postoperative days 1 (score, 19 15 vs. 37 20; P=0.003) and 2 (score, 11 10 vs. 19 13; P=0.031). Recovery and postoperative hospital stay were similar in both groups. There were no complications associated with the procedure.
The TAP block procedure is beneficial in reducing postoperative pain and early morphine requirements in laparoscopic live-donor nephrectomy.
Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is an autoimmune condition caused by immunoglobulin (Ig)G antibodies directed against the NR1 subunit of the NMDA glutamate receptor. ...Approximately 65% of cases present with psychiatric symptoms, particularly psychosis. It remains to be established whether anti-NMDA receptor antibodies can cause a 'purely' psychotic illness without overt neurological symptoms.
We conducted a systematic literature search to establish what proportion of patients with schizophrenia and related psychoses have antibodies directed against the NMDA receptor. Studies were included if (a) subjects had a diagnosis of schizophrenia, schizophrenia spectrum disorder or first-episode psychosis (FEP) using standard criteria, (b) serum was analysed for the presence of anti-NMDA receptor antibodies; and (c) the purpose of the study was to look for the presence of anti-NMDA receptor antibodies in patients with a primary psychiatric diagnosis without clinical signs of encephalitis.
Seven studies were included, comprising 1441 patients, of whom 115 7.98%, 95% confidence interval (CI) 6.69-9.50 were anti-NMDA receptor antibody positive. Of these, 21 (1.46%, 95% CI 0.94-2.23) patients were positive for antibodies of the IgG subclass. Prevalence rates were greater in cases than controls only for IgG antibodies; other subclasses are of less certain aetiological relevance. There was significant heterogeneity in terms of patient characteristics and the antibody assay used.
A minority of patients with psychosis are anti-NMDA receptor antibody positive. It remains to be established whether this subset of patients differs from antibody-negative patients in terms of underlying pathology and response to antipsychotic treatment, and whether immunomodulatory treatments are effective in alleviating psychotic symptoms in this group.
Seasonal progression of dissolved iron (DFe) concentrations in the upper water column was examined during four occupations in the Atlantic sector of the Southern Ocean. DFe inventories from euphotic ...and aphotic reservoirs decreased progressively from July to February, while dissolved inorganic nitrogen decreased from July to January with no significant change between January and February. Results suggest that between July and January, DFe loss from both euphotic and aphotic reservoirs was predominantly in support of phytoplankton growth (iron‐to‐carbon uptake ratio of 16 ± 3 μmol/mol), highlighting the importance of the “winter DFe reservoir” for biological uptake. During January to February, excess loss of DFe relative to dissolved inorganic nitrogen (iron‐to‐carbon uptake ratio of 44 ± 8 μmol/mol and aphotic DFe loss rate of 0.34 ± 0.06 μmol·m−2·day−1) suggests that scavenging is the dominant removal mechanism of DFe from the aphotic, while continued production is likely supported by recycled nutrients.
Plain Language Summary
Trace metal iron is one of the limiting nutrients for primary productivity in the Southern Ocean; however, the relative importance of seasonal iron supply and sinks remains poorly understood, due to sparse data coverage across the seasonal cycle and lack of high‐resolution dissolved iron (DFe) measurements. Here we present four “snapshots” of DFe measurements at a single station in the southeast Southern Atlantic Ocean (one in winter and three in late spring‐summer), to address the seasonal evolution of DFe and dissolved inorganic nitrogen (DIN) concentrations within the biologically active sunlit and subsurface reservoirs. We observed a seasonal depletion of DFe inventories from July to February, while DIN inventories decrease from July to January with no concomitant changes between January and February. This suggests that in addition to biological uptake in the sunlit layer, the observed decrease in DFe inventories below this (relative to DIN) is driven by aggregation and incorporation of iron particles into larger “marine snow” sinking particles, while nutrient recycling is driving the observed continuation of primary productivity during late summer. Our results provide insight into seasonal change of DFe availability in different reservoirs where interplay between removal and supply processes are controlling its distributions and bioavailability to support upper surface primary production.
Key Points
We report the first seasonal changes of the upper surface dissolved iron concentrations of four occupations from late winter to late summer
Euphotic zone dissolved iron decreases due to biological uptake, while aphotic iron decreases due to colloidal aggregation and scavenging
Recycling of nutrients might be responsible for sustaining the observed seasonal primary production in late January to early February
A short period of ex vivo normothermic perfusion (EVNP) immediately before transplantation can revive the kidney and reduce the effects of cold ischemic (CI) injury. Herein, we report a clinical case ...of EVNP carried out at an intermediate period of the preservation interval. The kidney was retrieved from a 63‐year‐old extended criteria donor. After 10 h 29 min of CI the kidney underwent EVNP with 1 unit of compatible packed red blood cells mixed with a priming solution at 35.0°C while the recipient was being prepared for surgery. The mean renal blood flow was 93.6 mL/min/100 g and the kidney produced 60 mL of urine. Shortly after the start of surgery the first intended recipient became unfit for transplantation. After 60 min EVNP the kidney was flushed with cold preservation solution and re‐packed in ice. The second period of CI was 5 h and 21 min. The kidney was transplanted without any complications into a 54‐year‐old predialysis patient. The recipient had immediate graft function with serum creatinine levels falling from 315 to 105 µmol/L by day 7. This is the first report of an intermediate period of EVNP in clinical renal transplantation. This case demonstrates the feasibility and safety of the technique.
This case describes the practicality of an intermediate period of ex vivo normothermic kidney perfusion.
Background
A significant proportion of donation after circulatory death (DCD) kidneys are declined for transplantation because of concerns over their quality. Ex vivo normothermic machine perfusion ...(NMP) provides a unique opportunity to assess the quality of a kidney and determine its suitability for transplantation.
Methods
In phase 1 of this study, declined human DCD kidneys underwent NMP assessment for 60 min. Kidneys were graded 1–5 using a quality assessment score (QAS) based on macroscopic perfusion, renal blood flow and urine output during NMP. In phase 2 of the study, declined DCD kidneys were assessed by NMP with an intention to transplant them.
Results
In phase 1, 18 of 42 DCD kidneys were declined owing to poor in situ perfusion. After NMP, 28 kidneys had a QAS of 1–3, and were considered suitable for transplantation. In phase 2, ten of 55 declined DCD kidneys underwent assessment by NMP. Eight kidneys had been declined because of poor in situ flushing in the donor and five of these were transplanted successfully. Four of the five kidneys had initial graft function.
Conclusion
NMP technology can be used to increase the number of DCD kidney transplants by assessing their quality before transplantation.
Increases available kidneys
PDF
