Many donor lungs do not meet current criteria for transplantation. In this study, ex vivo lung perfusion and ventilation allowed the successful transplantation of lungs that might otherwise have been ...considered unsuitable as transplants.
Lung transplantation is lifesaving for patients with end-stage lung diseases. However, the number of patients waiting for a lung transplant greatly exceeds the number of available donors. On average, only 15% of lungs from multiorgan donors are used for transplantation
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; the rest are considered unsuitable owing to the lung injury that occurs after brain death and to complications associated with treatment in the intensive care unit (ICU) (e.g., barotrauma and pulmonary edema). Although nonstandard donor lungs (i.e., lungs with suboptimal gas-exchange function or infiltrates visible on chest radiographs)
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have been used successfully,
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,
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increased primary graft dysfunction — an . . .
Ex-vivo lung perfusion (EVLP) can be used to extend overall lung preservation time by splitting one long cold ischaemic time into two shorter ones and interposing an additional EVLP time. We assessed ...the outcomes after clinical transplantation of lungs with more than 12 h of preservation time.
For this retrospective study, we searched the Toronto Lung Transplant Program database for patients who had received at least one lung transplant between Jan 1, 2006, and April 30, 2015, at a single hospital in Toronto, Canada. We split the identified patients into those with a total preservation time of more than 12 h and those with a total preservation time of less than 12 h to act as the control group. Total preservation time was defined as the sum of first cold ischaemic time, EVLP time, and second cold ischaemic time. We excluded patients if they had received a heart-lung transplant or were younger than 18 years. In bilateral lung transplantations, we used the longer preservation time of the two lungs for analysis. Lung preservation was done according to present standards of care and EVLP was done according to the Toronto EVLP technique. The primary outcomes were survival and International Society for Heart and Lung Transplantation Primary Graft Dysfunction (PGD) grade at 72 h post-transplantation. We compared outcomes with our control group using univariable and multivariable models.
We identified 906 patients who met eligibility criteria and had sufficient data for analysis (<12 h group n=809; mean lung preservation time 400·8 min SD 121·8 vs >12 h group n=97; 875·7 min 109·0). Median hospital and intensive-care unit length of stay were similar between the less than 12 h group and the more than 12 h group (hospital stay: 23 days 16-42 vs 25·5 days 17-50·25, p=0·60; intensive-care unit stay: 4 days 2-14 vs 4 days 2-16, p=0·53). PGD grade was also not different between the two groups at 72 h post-transplantation (p=0·85). There was also no difference in survival between the two groups as shown on Kaplan-Meier survival curves (p=0·61). Multivariable survival analysis using Cox's model showed increasing recipient age to be a significant variable affecting survival.
Extension of graft preservation time beyond 12 h with EVLP does not negatively affect early lung transplantation outcomes. Extension of clinical lung preservation times might allow for more transplantations to be done as a result of improved facilitation and increased flexibility around timing of lung transplantation operations.
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Ex vivo lung perfusion (EVLP) is being increasingly applied as a method to evaluate and treat donor lungs for transplantation. However, with the previous limited worldwide experience, no studies have ...been able to evaluate the impact of indication for EVLP on organ utilization rates and recipient outcomes after lung transplantation (LTx). We examined these outcomes in a large-cohort, single-center series of clinical EVLP cases.
All EVLP procedures performed at our institution between October 2008 and December 2017 were examined. The EVLPs were divided into 4 groups based on the indication for the procedure: group 1, high-risk brain death donors (HR-BDD); group 2, standard-risk donation after cardiac death (S-DCD); group 3, high-risk donation after cardiac death (HR-DCD); and group 4, logistics (LOGISTICS, the need for prolongation of preservation time or organ retrieval by a different transplantation team).
During the study period, a total of 1106 lung transplants were performed in our institution. In this period, 372 EVLPs were performed, 255 (69%) of which were accepted for transplantation, resulting in 262 transplants. Utilization rates were 70% (140 of 198) for group 1, 82% (40 of 49) for group 2, 63% (69 of 109) for group 3, and 81% (13 of 16) for group 4 (P = .42, Fisher's exact test). Recipient age (P = .27) and medical diagnosis (P = .31) were not different across the 4 groups. Kaplan–Meier survival by EVLP indication group demonstrated no differences. Thirty-day mortality was 2.1% in group 1, 5% in group 2, 2.9% in group 3, and 0% in group 4 (P = .87, Fisher's exact test). The median days of mechanical ventilation, intensive care unit stay, and hospital stay were 2, 4, and 21 in group 1; 2, 3, and 21 in group 2; 3, 5, and 28 in group 3; and 2, 4, and 17 in group 4 (P = .29, .17, and .09, respectively, Kruskal–Wallis rank-sum test).
Clinical implementation of EVLP has allowed our program to expand the annual lung transplantation activity by 70% in this time period. It has improved confidence in the utilization of DCD lungs and BDD lungs, with an average 70% utilization of post-EVLP treated donor lungs with excellent outcomes, while addressing significant challenges in donor lung assessment and the logistics of “real-life” clinical lung transplantation.
Eusocial insects provide special opportunities to elucidate the evolution of ageing as queens have apparently evaded costs of reproduction and reversed the fecundity–longevity trade-off generally ...observed in non-social organisms. But how reproduction affects longevity in eusocial insects has rarely been tested experimentally. In this study, we took advantage of the reproductive plasticity of workers to test the causal role of reproduction in determining longevity in eusocial insects. Using the eusocial bumblebee Bombus terrestris, we found that, in whole colonies, in which workers could freely ‘choose’ whether to become reproductive, workers' level of ovarian activation was significantly positively associated with longevity and ovary-active workers significantly outlived ovary-inactive workers. By contrast, when reproductivity was experimentally induced in randomly selected workers, thereby decoupling it from other traits, workers' level of ovarian activation was significantly negatively associated with longevity and ovary-active workers were significantly less long-lived than ovary-inactive workers. These findings show that workers experience costs of reproduction and suggest that intrinsically high-quality individuals can overcome these costs. They also raise the possibility that eusocial insect queens exhibit condition-dependent longevity and hence call into question whether eusociality entails a truly reversed fecundity–longevity trade-off involving a fundamental remodelling of conserved genetic and endocrine networks underpinning ageing.
Autism spectrum disorders (ASDs) are an early onset, heterogeneous group of heritable neuropsychiatric disorders with symptoms that include deficits in social interaction skills, impaired ...communication abilities, and ritualistic-like repetitive behaviours. One of the hypotheses for a common molecular mechanism underlying ASDs is altered translational control resulting in exaggerated protein synthesis. Genetic variants in chromosome 4q, which contains the EIF4E locus, have been described in patients with autism. Importantly, a rare single nucleotide polymorphism has been identified in autism that is associated with increased promoter activity in the EIF4E gene. Here we show that genetically increasing the levels of eukaryotic translation initiation factor 4E (eIF4E) in mice results in exaggerated cap-dependent translation and aberrant behaviours reminiscent of autism, including repetitive and perseverative behaviours and social interaction deficits. Moreover, these autistic-like behaviours are accompanied by synaptic pathophysiology in the medial prefrontal cortex, striatum and hippocampus. The autistic-like behaviours displayed by the eIF4E-transgenic mice are corrected by intracerebroventricular infusions of the cap-dependent translation inhibitor 4EGI-1. Our findings demonstrate a causal relationship between exaggerated cap-dependent translation, synaptic dysfunction and aberrant behaviours associated with autism.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Ex vivo lung perfusion (EVLP) is an effective method to assess and improve the function of otherwise unacceptable lungs, alleviating the shortage of donor lungs. The early results with EVLP have been ...encouraging, but longer-term results, including functional and patient-reported outcomes, are not well characterized.
This retrospective single-center study included all lung transplants performed between September 2008 and December 2012. We investigated whether survival or rate of chronic lung allograft dysfunction (CLAD) differed in recipients of EVLP-treated lungs compared with contemporaneous recipients of conventional donor lungs. We also studied functional (highest forced expiratory volume in 1 second predicted, change in 6-minute walk distance, number of acute rejection episodes) and quality of life outcomes.
Of 403 lung transplants that were performed, 63 patients (15.6%) received EVLP-treated allografts. Allograft survival for EVLP and conventional donor lung recipients was 79% vs 85%, 71% vs 73%, and 58% vs 57% at 1, 3, and 5 years after transplant, respectively (log-rank p = not significant). Freedom from CLAD was also similar (log-rank p = 0.53). There were no significant differences in functional outcomes such as highest forced expiratory volume in 1 second predicted (76.5% ± 23.8% vs 75.8% ± 22.8%, p = 0.85), change in 6-minute walk distance (194 ± 108 meters vs 183 ± 126 meters, p = 0.57), or the number of acute rejection episodes (1.5 ± 1.4 vs 1.3 ± 1.3, p = 0.36). The EVLP and conventional donor groups both reported a significantly improved quality of life after transplantation, but there was no intergroup difference.
EVLP is a safe and effective method of assessing and using high-risk donor lungs before transplantation and leads to acceptable long-term survival, graft function, and improvements of quality of life that are comparable with conventionally selected donor lungs.
Abstract During extensive periods without rain, known as dry-downs, decreasing soil moisture (SM) induces plant water stress at the point when it limits evapotranspiration, defining a critical SM ...threshold (θ crit ). Better quantification of θ crit is needed for improving future projections of climate and water resources, food production, and ecosystem vulnerability. Here, we combine systematic satellite observations of the diurnal amplitude of land surface temperature (dLST) and SM during dry-downs, corroborated by in-situ data from flux towers, to generate the observation-based global map of θ crit . We find an average global θ crit of 0.19 m 3 /m 3 , varying from 0.12 m 3 /m 3 in arid ecosystems to 0.26 m 3 /m 3 in humid ecosystems. θ crit simulated by Earth System Models is overestimated in dry areas and underestimated in wet areas. The global observed pattern of θ crit reflects plant adaptation to soil available water and atmospheric demand. Using explainable machine learning, we show that aridity index, leaf area and soil texture are the most influential drivers. Moreover, we show that the annual fraction of days with water stress, when SM stays below θ crit , has increased in the past four decades. Our results have important implications for understanding the inception of water stress in models and identifying SM tipping points.
Bumblebees (Bombus species) are major pollinators of commercial crops and wildflowers but factors affecting their abundance, including causes of recent population declines, remain unclear. ...Investigating the ecology of species with expanding ranges provides a potentially powerful means of elucidating these factors. Such species may also bring novel pollination services to their new ranges. We therefore investigated landscape-scale habitat use and foraging preferences of the Tree Bumblebee, B. hypnorum, a recent natural colonist that has rapidly expanded its range in the UK over the past decade. Counts of B. hypnorum and six other Bombus species were made in March-June 2012 within a mixed landscape in south-eastern Norfolk, UK. The extent of different landscape elements around each transect was quantified at three scales (250 m, 500 m and 1500 m). We then identified the landscape elements that best predicted the density of B. hypnorum and other Bombus species. At the best fitting scale (250 m), B. hypnorum density was significantly positively associated with extent of both urban and woodland cover and significantly negatively associated with extent of oilseed rape cover. This combination of landscape predictors was unique to B. hypnorum. Urban and woodland cover were associated with B. hypnorum density at three and two, respectively, of the three scales studied. Relative to other Bombus species, B. hypnorum exhibited a significantly higher foraging preference for two flowering trees, Crataegus monogyna and Prunus spinosa, and significantly lower preferences for Brassica napus, Glechoma hederacea and Lamium album. Our study provides novel, quantitative support for an association of B. hypnorum with urban and woodland landscape elements. Range expansion in B. hypnorum appears to depend, on exploitation of widespread habitats underutilised by native Bombus species, suggesting B. hypnorum will readily co-exist with these species. These findings suggest that management could target bumblebee species with distinctive habitat requirements to help maintain pollination services.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The increasing frequency and intensity of climate extremes and complex ecosystem responses motivate the need for integrated observational studies at low-latency to determine biosphere responses and ...carbon-climate feedbacks. Here, we develop a satellite-based rapid attribution workflow and demonstrate its use at a 1–2-month latency to attribute drivers of the carbon cycle feedbacks during the 2020-2021 Western US drought and heatwave. In the first half of 2021, concurrent negative photosynthesis anomalies and large positive column CO2 anomalies were detected with satellites. Using a simple atmospheric mass balance approach, we estimate a surface carbon efflux anomaly of 132 TgC in June 2021, a magnitude corroborated 28 independently with a dynamic global vegetation model. Integrated satellite observations of hydrologic processes, representing the soil-plant-atmosphere continuum (SPAC), show that these surface carbon flux anomalies are largely due to substantial reductions in photosynthesis because of a spatially widespread moisture-deficit propagation through the SPAC between 2020 and 2021. A causal model indicates deep soil moisture stores partially drove photosynthesis, maintaining its values in 2020 and driving its declines throughout 2021. The causal model also suggests legacy effects may have amplified photosynthesis deficits in 2021 beyond the direct effects of environmental forcing. The integrated, observation framework presented here provides a valuable first assessment of a biosphere extreme response and an independent testbed for improving drought propagation and mechanisms in models. The rapid identification of extreme carbon anomalies and hotspots can also aid mitigation and adaptation decisions.
Objective To analyze the outcomes of patients with pulmonary arterial hypertension referred for lung transplantation and determine the changes over time. Methods All patients with pulmonary arterial ...hypertension referred for lung transplantation in our program from January 1997 to September 2010 were reviewed. Pulmonary arterial hypertension was classified as idiopathic (n = 123) or associated with congenital heart disease (n = 77), connective tissue disease (n = 102), or chronic thromboembolic disease (n = 14). Results After completing their assessment, 61 patients (19%) were found to be unsuitable for lung transplantation, 38 (12%) refused lung transplantation, 65 (21%) were too early to be listed, and 48 (15%) died before their assessment (n = 34) or being listed (n = 14). Of the 100 patients listed for lung transplantation, 57 underwent bilateral lung transplantation, 22 underwent heart–lung transplantation, 18 died while waiting, and 3 were still waiting. The waiting list mortality was the greatest for patients with connective tissue disease–pulmonary arterial hypertension (34% vs 11% in the remaining patients, P = .005). The number of patients admitted to the hospital to be bridged to lung transplantation increased from 7% in the 1997–2004 cohort to 25% in the 2005–2010 cohort ( P = .02). After lung transplantation, the 30-day mortality decreased from 24% in the 1997–2004 group to 6% in the 2005–2010 group ( P = .007). The 10-year survival was worse for those with idiopathic pulmonary arterial hypertension (42% vs 70% for the remaining patients, P = .01). The long-term survival reached 69% at 10 years in the patients with connective tissue disease pulmonary arterial hypertension. Conclusions Lung transplantation is an option for about one third of the patients with pulmonary arterial hypertension referred for lung transplantation. The 30-day mortality after lung transplantation improved significantly over time, but the long-term survival remained similar between the two cohorts. Patients with connective tissue disease–pulmonary arterial hypertension have a high mortality on the waiting list but excellent long-term survival.
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