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Native to Central and Eastern Europe, the euryhaline pikeperch Sander lucioperca can acclimatize to elevated salinity levels (e.g., up to 30), but it remains unknown whether their invasive populations use this ability to inhabit and/or disperse through brackish waters, such as estuaries and inshore areas. To test whether invasive pikeperch show a propensity to move into areas of relatively high salinity, their spatial use and movement patterns (e.g., home range, distances moved, and movement rates) were assessed using acoustic telemetry in the upper River Thames estuary, southeast England. Analyses revealed that individual pikeperch were capable of moving relatively long distances in a short time (e.g., speeds up to 70 m min-1), with movement patterns associated more with tidal state and elevation at the water surface (both assumed to relate to changes in salinity) than diurnal changes. There were no recorded movements of any pikeperch into the more saline, downstream waters of the estuary where salinity levels were recorded to over 40, with the mean salinity in the most downstream area where pikeperch were detected being 1.39 (range of logger: 1.22-1.71). The results suggest that these pikeperch did not use high salinity waters when less saline waters were available, and thus the risk that they will use to move through high salinity areas to expand their invasive range appears low. Accordingly, efforts to minimize risks of the further dispersal of invasive pikeperch populations can focus on control and containment programmes within fresh waters.
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Hereditary haemorrhagic telangiectasia is a genetic condition of abnormal blood vessel formation resulting from an imbalance of pro- and anti-angiogenic products of the transforming growth factor ß/bone morphogenetic protein signalling pathway which contributes to vascular remodelling and maintenance. Hepatic vascular malformations are common although less frequently symptomatic, but may result in high-output cardiac failure, portal hypertension and biliary ischaemia. Whilst the understanding of the genetic and cell signalling pathways that are the hallmark of hereditary haemorrhagic telangiectasia have been clarified, there remain challenges in therapy for these patients. Only patients with symptomatic hepatic vascular malformations require treatment, with most (63%) responding to first-line medical therapy. For non-responders, bevacizumab is effective in reducing cardiac output in those with heart failure secondary to hepatic vascular malformations as well as other manifestations of the disease. Although liver transplantation is the only curative option, optimal timing is critical. Novel anti-angiogenetic drugs and those that target aberrant cell signalling pathway are being explored.
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Trasplante de Hígado , Telangiectasia Hemorrágica Hereditaria , Humanos , Telangiectasia Hemorrágica Hereditaria/complicaciones , Telangiectasia Hemorrágica Hereditaria/genética , Inhibidores de la Angiogénesis/uso terapéutico , Hígado/irrigación sanguínea , Transducción de Señal , Hipertensión Portal/etiología , Hipertensión Portal/fisiopatología , Bevacizumab/uso terapéuticoRESUMEN
Background: Anaesthesiology clinicians can implement risk mitigation strategies if they know which patients are at greatest risk for postoperative complications. Although machine learning models predicting complications exist, their impact on clinician risk assessment is unknown. Methods: This single-centre randomised clinical trial enrolled patients age ≥18 undergoing surgery with anaesthesiology services. Anaesthesiology clinicians providing remote intraoperative telemedicine support reviewed electronic health records with (assisted group) or without (unassisted group) also reviewing machine learning predictions. Clinicians predicted the likelihood of postoperative 30-day all-cause mortality and postoperative acute kidney injury within 7 days. Area under the receiver operating characteristic curve (AUROC) for the clinician predictions was determined. Results: Among 5,071 patient cases reviewed by 89 clinicians, the observed incidence was 2% for postoperative death and 11% for acute kidney injury. Clinician predictions agreed with the models more strongly in the assisted versus unassisted group (weighted kappa 0.75 versus 0.62 for death [difference 0.13, 95%CI 0.10-0.17] and 0.79 versus 0.54 for kidney injury [difference 0.25, 95%CI 0.21-0.29]). Clinicians predicted death with AUROC of 0.793 in the assisted group and 0.780 in the unassisted group (difference 0.013, 95%CI -0.070 to 0.097). Clinicians predicted kidney injury with AUROC of 0.734 in the assisted group and 0.688 in the unassisted group (difference 0.046, 95%CI -0.003 to 0.091). Conclusions: Although there was evidence that the models influenced clinician predictions, clinician performance was not statistically significantly different with and without machine learning assistance. Further work is needed to clarify the role of machine learning in real-time perioperative risk stratification. Trial Registration: ClinicalTrials.gov NCT05042804.
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Background: Novel applications of telemedicine can improve care quality and patient outcomes. Telemedicine for intraoperative decision support has not been rigorously studied. Methods: This single centre randomised clinical trial ( clinicaltrials.gov NCT03923699 ) of unselected adult surgical patients was conducted between July 1, 2019 and January 31, 2023. Patients received usual care or decision support from a telemedicine service, the Anesthesiology Control Tower (ACT). The ACT provided real-time recommendations to intraoperative anaesthesia clinicians based on case reviews, machine-learning forecasting, and physiologic alerts. ORs were randomised 1:1. Co-primary outcomes of 30-day all-cause mortality, respiratory failure, acute kidney injury (AKI), and delirium were analysed as intention-to-treat. Results: The trial completed planned enrolment with 71927 surgeries (35956 ACT; 35971 usual care). After multiple testing correction, there was no significant effect of the ACT vs. usual care on 30-day mortality [641/35956 (1.8%) vs 638/35971 (1.8%), risk difference 0.0% (95% CI -0.2% to 0.3%), p=0.96], respiratory failure [1089/34613 (3.1%) vs 1112/34619 (3.2%), risk difference -0.1% (95% CI -0.4% to 0.3%), p=0.96], AKI [2357/33897 (7%) vs 2391/33795 (7.1%), risk difference -0.1% (-0.6% to 0.4%), p=0.96], or delirium [1283/3928 (32.7%) vs 1279/3989 (32.1%), risk difference 0.6% (-2.0% to 3.2%), p=0.96]. There were no significant differences in secondary outcomes or in sensitivity analyses. Conclusions: In this large RCT of a novel application of telemedicine-based remote monitoring and decision support using real-time alerts and case reviews, we found no significant differences in postoperative outcomes. Large-scale intraoperative telemedicine is feasible, and we suggest future avenues where it may be impactful.
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Aneuploidy, having an aberrant genome, is gaining increasing attention in neurodegenerative diseases. It gives rise to proteotoxic stress as well as a stereotypical oxidative shift which makes these cells sensitive to internal and environmental stresses. A growing body of research from numerous laboratories suggests that many neurodegenerative disorders, especially Alzheimer's disease and frontotemporal dementia, are characterised by neuronal aneuploidy and the ensuing apoptosis, which may contribute to neuronal loss. Using Drosophila as a model, we investigated the effect of induced aneuploidy in GABAergic neurons. We found an increased proportion of aneuploidy due to Mad2 depletion in the third-instar larval brain and increased cell death. Depletion of Mad2 in GABAergic neurons also gave a defective climbing and seizure phenotype. Feeding animals an antioxidant rescued the climbing and seizure phenotype. These findings suggest that increased aneuploidy leads to higher oxidative stress in GABAergic neurons which causes cell death, climbing defects, and seizure phenotype. Antioxidant feeding represents a potential therapy to reduce the aneuploidy-driven neurological phenotype.
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Aneuploidia , Neuronas GABAérgicas , Estrés Oxidativo , Fenotipo , Animales , Neuronas GABAérgicas/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Antioxidantes/farmacología , Antioxidantes/metabolismo , Convulsiones/genética , Convulsiones/metabolismo , Drosophila melanogaster/genética , Encéfalo/metabolismo , Drosophila/genéticaRESUMEN
This study provides a regional picture of long-term changes in Atlantic salmon growth at the southern edge of their distribution, using a multi-population approach spanning 49 years and five populations. We provide empirical evidence of salmon life history being influenced by a combination of common signals in the marine environment and population-specific signals. We identified an abrupt decline in growth from 1976 and a more recent decline after 2005. As these declines have also been recorded in northern European populations, our study significantly expands a pattern of declining marine growth to include southern European populations, thereby revealing a large-scale synchrony in marine growth patterns for almost five decades. Growth increments during their sea sojourn were characterized by distinct temporal dynamics. At a coarse temporal resolution, growth during the first winter at sea seemed to gradually improve over the study period. However, the analysis of finer seasonal growth patterns revealed ecological bottlenecks of salmon life histories at sea in time and space. Our study reinforces existing evidence of an impact of early marine growth on maturation decision, with small-sized individuals at the end of the first summer at sea being more likely to delay maturation. However, each population was characterized by a specific probabilistic maturation reaction norm, and a local component of growth at sea in which some populations have better growth in some years might further amplify differences in maturation rate. Differences between populations were smaller than those between sexes, suggesting that the sex-specific growth threshold for maturation is a well-conserved evolutionary phenomenon in salmon. Finally, our results illustrate that although most of the gain in length occurs during the first summer at sea, the temporal variability in body length at return is buffered against the decrease in post-smolt growth conditions. The intricate combination of growth over successive seasons, and its interplay with the maturation decision, could be regulating body length by maintaining diversity in early growth trajectories, life histories, and the composition of salmon populations.
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Salmo salar , Humanos , Animales , Ríos , Europa (Continente) , Evolución Biológica , Estaciones del AñoRESUMEN
Ectopic variceal bleeding is a rare cause of gastrointestinal bleeding that can occur in settings of cirrhotic and non-cirrhotic portal hypertension and is characterised by its development at locations remote from the oesophagus and stomach. Ectopic varices can be difficult to identify and access, and, although a relatively uncommon cause of portal hypertensive bleeding, can represent a difficult diagnostic and therapeutic challenge associated with considerable mortality. Low incidence and variance in variceal anatomy preclude large randomised controlled trials, and clinical practice is based on experience from case reports, case series, and specialist centre expertise. Optimisation of survival outcomes relies on understanding a patient's portal venous anatomy and functional hepatic reserve to guide timely and targeted endoscopic and endovascular interventions to facilitate the rapid control of ectopic variceal bleeding.
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Várices Esofágicas y Gástricas , Hipertensión Portal , Várices , Humanos , Várices Esofágicas y Gástricas/diagnóstico , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/terapia , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/terapia , Hipertensión Portal/complicaciones , Hipertensión Portal/diagnóstico , Várices/complicaciones , Várices/diagnóstico , Vena PortaRESUMEN
Importance: Telemedicine for clinical decision support has been adopted in many health care settings, but its utility in improving intraoperative care has not been assessed. Objective: To pilot the implementation of a real-time intraoperative telemedicine decision support program and evaluate whether it reduces postoperative hypothermia and hyperglycemia as well as other quality of care measures. Design, Setting, and Participants: This single-center pilot randomized clinical trial (Anesthesiology Control Tower-Feedback Alerts to Supplement Treatments [ACTFAST-3]) was conducted from April 3, 2017, to June 30, 2019, at a large academic medical center in the US. A total of 26 254 adult surgical patients were randomized to receive either usual intraoperative care (control group; n = 12 980) or usual care augmented by telemedicine decision support (intervention group; n = 13 274). Data were initially analyzed from April 22 to May 19, 2021, with updates in November 2022 and February 2023. Intervention: Patients received either usual care (medical direction from the anesthesia care team) or intraoperative anesthesia care monitored and augmented by decision support from the Anesthesiology Control Tower (ACT), a real-time, live telemedicine intervention. The ACT incorporated remote monitoring of operating rooms by a team of anesthesia clinicians with customized analysis software. The ACT reviewed alerts and electronic health record data to inform recommendations to operating room clinicians. Main Outcomes and Measures: The primary outcomes were avoidance of postoperative hypothermia (defined as the proportion of patients with a final recorded intraoperative core temperature >36 °C) and hyperglycemia (defined as the proportion of patients with diabetes who had a blood glucose level ≤180 mg/dL on arrival to the postanesthesia recovery area). Secondary outcomes included intraoperative hypotension, temperature monitoring, timely antibiotic redosing, intraoperative glucose evaluation and management, neuromuscular blockade documentation, ventilator management, and volatile anesthetic overuse. Results: Among 26 254 participants, 13 393 (51.0%) were female and 20 169 (76.8%) were White, with a median (IQR) age of 60 (47-69) years. There was no treatment effect on avoidance of hyperglycemia (7445 of 8676 patients [85.8%] in the intervention group vs 7559 of 8815 [85.8%] in the control group; rate ratio [RR], 1.00; 95% CI, 0.99-1.01) or hypothermia (7602 of 11 447 patients [66.4%] in the intervention group vs 7783 of 11 672 [66.7.%] in the control group; RR, 1.00; 95% CI, 0.97-1.02). Intraoperative glucose measurement was more common among patients with diabetes in the intervention group (RR, 1.07; 95% CI, 1.01-1.15), but other secondary outcomes were not significantly different. Conclusions and Relevance: In this randomized clinical trial, anesthesia care quality measures did not differ between groups, with high confidence in the findings. These results suggest that the intervention did not affect the targeted care practices. Further streamlining of clinical decision support and workflows may help the intraoperative telemedicine program achieve improvement in targeted clinical measures. Trial Registration: ClinicalTrials.gov Identifier: NCT02830126.
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Hiperglucemia , Hipotermia , Adulto , Humanos , Femenino , Persona de Mediana Edad , Anciano , Masculino , Hipotermia/prevención & control , Hiperglucemia/prevención & control , Grupos Control , Centros Médicos Académicos , GlucosaRESUMEN
Aneuploidy, or having a disrupted genome, is an aberration commonly found in tumours but rare in normal tissues. It gives rise to proteotoxic stress as well as a stereotypical oxidative shift, which makes these cells sensitive to internal and environmental stresses. Using Drosophila as a model, we investigated the changes in transcription in response to ongoing changes to ploidy (chromosomal instability, CIN). We noticed changes in genes affecting one-carbon metabolism, specifically those affecting the production and use of s-adenosyl methionine (SAM). The depletion of several of these genes has led to cell death by apoptosis in CIN cells but not in normal proliferating cells. We found that CIN cells are particularly sensitive to SAM metabolism at least partly because of its role in generating polyamines. Feeding animals spermine was seen to rescue the cell death caused by the loss of SAM synthase in CIN tissues. The loss of polyamines led to decreased rates of autophagy and sensitivity to reactive oxygen species (ROS), which we have shown to contribute significantly to cell death in CIN cells. These findings suggest that a well-tolerated metabolic intervention such as polyamine inhibition has the potential to target CIN tumours via a relatively well-characterised mechanism.
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INTRODUCTION: Millions of patients receive general anaesthesia for surgery annually. Crucial gaps in evidence exist regarding which technique, propofol total intravenous anaesthesia (TIVA) or inhaled volatile anaesthesia (INVA), yields superior patient experience, safety and outcomes. The aim of this pilot study is to assess the feasibility of conducting a large comparative effectiveness trial assessing patient experiences and outcomes after receiving propofol TIVA or INVA. METHODS AND ANALYSIS: This protocol was cocreated by a diverse team, including patient partners with personal experience of TIVA or INVA. The design is a 300-patient, two-centre, randomised, feasibility pilot trial. Patients 18 years of age or older, undergoing elective non-cardiac surgery requiring general anaesthesia with a tracheal tube or laryngeal mask airway will be eligible. Patients will be randomised 1:1 to propofol TIVA or INVA, stratified by centre and procedural complexity. The feasibility endpoints include: (1) proportion of patients approached who agree to participate; (2) proportion of patients who receive their assigned randomised treatment; (3) completeness of outcomes data collection and (4) feasibility of data management procedures. Proportions and 95% CIs will be calculated to assess whether prespecified thresholds are met for the feasibility parameters. If the lower bounds of the 95% CI are above the thresholds of 10% for the proportion of patients agreeing to participate among those approached and 80% for compliance with treatment allocation for each randomised treatment group, this will suggest that our planned pragmatic 12 500-patient comparative effectiveness trial can likely be conducted successfully. Other feasibility outcomes and adverse events will be described. ETHICS AND DISSEMINATION: This study is approved by the ethics board at Washington University (IRB# 202205053), serving as the single Institutional Review Board for both participating sites. Recruitment began in September 2022. Dissemination plans include presentations at scientific conferences, scientific publications, internet-based educational materials and mass media. TRIAL REGISTRATION NUMBER: NCT05346588.
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Propofol , Humanos , Adolescente , Adulto , Propofol/efectos adversos , Proyectos Piloto , Estudios de Factibilidad , Anestesia General , Administración Intravenosa , Anestesia Intravenosa/efectos adversosRESUMEN
BACKGROUND: The STRIDeR (Support Tool for Re-Irradiation Decisions guided by Radiobiology) project aims to create a clinically viable re-irradiation planning pathway within a commercial treatment planning system (TPS). Such a pathway should account for previously delivered dose, voxel-by-voxel, taking fractionation effects, tissue recovery and anatomical changes into account. This work presents the workflow and technical solutions in the STRIDeR pathway. METHODS: The pathway was implemented in RayStation (version 9B DTK) to allow an original dose distribution to be used as background dose to guide optimisation of re-irradiation plans. Organ at risk (OAR) planning objectives in equivalent dose in 2 Gy fractions (EQD2) were applied cumulatively across the original and re-irradiation treatments, with optimisation of the re-irradiation plan performed voxel-by-voxel in EQD2. Different approaches to image registration were employed to account for anatomical change. Data from 21 patients who received pelvic Stereotactic Ablative Radiotherapy (SABR) re-irradiation were used to illustrate the use of the STRIDeR workflow. STRIDeR plans were compared to those produced using a standard manual method. RESULTS: The STRIDeR pathway resulted in clinically acceptable plans in 20/21 cases. Compared to plans produced using the laborious manual method, less constraint relaxation was required or higher re-irradiation doses could be prescribed in 3/21. CONCLUSION: The STRIDeR pathway used background dose to guide radiobiologically meaningful, anatomically-appropriate re-irradiation treatment planning within a commercial TPS. This provides a standardised and transparent approach, offering more informed re-irradiation and improved cumulative OAR dose evaluation.
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Radioterapia de Intensidad Modulada , Reirradiación , Humanos , Dosificación Radioterapéutica , Reirradiación/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Fraccionamiento de la Dosis de Radiación , Radioterapia de Intensidad Modulada/métodos , Órganos en Riesgo/efectos de la radiaciónAsunto(s)
Braquiterapia , Tumor de Células de la Granulosa , Neoplasias Hepáticas , Neoplasias Ováricas , Femenino , Humanos , Tumor de Células de la Granulosa/radioterapia , Tumor de Células de la Granulosa/patología , Neoplasias Hepáticas/terapia , Braquiterapia/efectos adversos , Neoplasias Ováricas/patologíaRESUMEN
Cancer metabolic reprogramming is essential for maintaining cancer cell survival and rapid replication. A common target of this metabolic reprogramming is one-carbon metabolism which is notable for its function in DNA synthesis, protein and DNA methylation, and antioxidant production. Polyamines are a key output of one-carbon metabolism with widespread effects on gene expression and signaling. As a result of these functions, one-carbon and polyamine metabolism have recently drawn a lot of interest for their part in cancer malignancy. Therapeutic inhibitors that target one-carbon and polyamine metabolism have thus been trialed as anticancer medications. The significance and future possibilities of one-carbon and polyamine metabolism as a target in cancer therapy are discussed in this review.
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Antineoplásicos , Neoplasias , Humanos , Carbono/metabolismo , Poliaminas/metabolismo , Metilación de ADN , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismoRESUMEN
OBJECTIVE: The Anesthesiology Control Tower (ACT) for operating rooms (ORs) remotely assesses the progress of surgeries and provides real-time perioperative risk alerts, communicating risk mitigation recommendations to bedside clinicians. We aim to identify and map ACT-OR nonroutine events (NREs)-risk-inducing or risk-mitigating workflow deviations-and ascertain ACT's impact on clinical workflow and patient safety. MATERIALS AND METHODS: We used ethnographic methods including shadowing ACT and OR clinicians during 83 surgeries, artifact collection, chart reviews for decision alerts sent to the OR, and 10 clinician interviews. We used hybrid thematic analysis informed by a human-factors systems-oriented approach to assess ACT's role and impact on safety, conducting content analysis to assess NREs. RESULTS: Across 83 cases, 469 risk alerts were triggered, and the ACT sent 280 care recommendations to the OR. 135 NREs were observed. Critical factors facilitating ACT's role in supporting patient safety included providing backup support and offering a fresh-eye perspective on OR decisions. Factors impeding ACT included message timing and ACT and OR clinician cognitive lapses. Suggestions for improvement included tailoring ACT message content (structure, timing, presentation) and incorporating predictive analytics for advanced planning. DISCUSSION: ACT served as a safety net with remote surveillance features and as a learning healthcare system with feedback/auditing features. Supporting strategies include adaptive coordination and harnessing clinician/patient support to improve ACT's sustainability. Study insights inform future intraoperative telemedicine design considerations to mitigate safety risks. CONCLUSION: Incorporating similar remote technology enhancement into routine perioperative care could markedly improve safety and quality for millions of surgical patients.
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Quirófanos , Telemedicina , Antropología Cultural , Humanos , Seguridad del Paciente , Flujo de TrabajoRESUMEN
Fish somatic growth is indeterminate and can be influenced by a range of abiotic and biotic variables. With climate change forecast to increase the frequency of warming and unusual discharge events, it is thus important to understand how these variables currently influence somatic growth and how that might differ for specific age-classes and/ or life stages. Here, we used a 17-year dataset from a chalk stream in southern England to identify the abiotic and biotic influences on the growth of juvenile, sub-adult and adult life stages of European grayling (Thymallus thymallus), a cold-water riverine salmonid. The results revealed that interannual variations in grayling growth were well described by annual- and site-specific abiotic and biotic explanatory variables. We found divergent responses between life stages to increased temperature and unusual discharge during the main growth period with, for example, elevated temperatures related to increased juvenile growth but reduced sub-adult growth, and high discharge events related to increased sub-adult growth yet reduced juvenile growth. Conversely, stage-specific grayling abundance negatively influenced growth at each life stage, though only juvenile growth was impacted by the abundance of a competitor species, brown trout (Salmo trutta). These results emphasise the merits of testing a wide range of environmental and biological explanatory variables on fish growth, and across life stages. They also reveal the importance of maintaining high habitat heterogeneity in rivers to ensure all life stages can reduce their competitive interactions and have access to adequate flow and thermal refugia during periods of elevated environmental stress.
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Salmonidae , Animales , Cambio Climático , Ecosistema , Ríos , Salmonidae/fisiología , Trucha/fisiologíaRESUMEN
Populations of Atlantic salmon Salmo salar have experienced precipitous declines in abundance since the 1970s. This decline has been associated with reduced numbers of adult salmon returning to fresh water from their marine migration, i.e., their marine return rates (MRR). Thus, understanding the factors that affect MRR is of crucial conservation importance. The authors used a state-space model with a 13-year time series of individually tagged salmon mark-recapture histories on the River Frome, southern England, to test the effect of smolt body length on their MRR. In addition to smolt length, the model tested for the influence of environmental covariates that were representative of the conditions experienced by the smolts in the early stages of their seaward migration, i.e., from the lower river to the estuary exit. The model indicated that, even when accounting for environmental covariates, smolt body length was an important predictor of MRR. Although larger smolts have a higher probability of returning to their natal river as adults than smaller smolts, and one-sea-winter salmon have a survival rate twice as high as multi-sea-winter salmon, the actual biological mechanisms underpinning this phenomenon remain uncertain. These results have important applications for salmon conservation, as efforts to bolster salmon populations in the freshwater environment should consider methods to improve smolt quality (i.e., body size) as well as smolt quantity.
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Migración Animal , Salmo salar , Animales , Estuarios , Ríos , Estaciones del AñoRESUMEN
Aquatic habitats are severely threatened by human activities. For anadromous species, managing freshwater habitats to maximize production of more, larger juveniles could improve resilience to threats in marine habitats and enhance population viability. In some juvenile salmonid habitats, complexity created by large substrates provides resources and reduces competitive interactions, thereby promoting juvenile production. In lowland rivers, which lack large substrates, aquatic plants might provide similar complexity and enhance fish productivity. To test the influence of aquatic plants on juvenile Atlantic salmon and sympatric brown trout in a lowland river, we directly manipulated the cover of the dominant macrophyte, Ranunculus, in nine sites during summer and autumn for two years. We quantified the abundance, site retention and growth of salmon and trout under high, medium or low Ranunculus cover. To investigate the effects of Ranunculus cover on feeding opportunities and interspecific competition, we quantified available prey biomass and body size, fish diet composition and compared dietary niche overlap. Experimentally increased Ranunculus cover supported higher salmon abundance in summer and autumn, and higher site retention and growth of salmon in summer. Trout abundance and growth were not influenced by Ranunculus cover, but trout site retention doubled in high, relative to low, cover sites. Despite the weak effects of Ranunculus cover on prey availability, salmon and trout inhabiting high cover sites consumed larger prey and a higher biomass of prey. Furthermore, dietary niche overlap was lower in high, relative to low, cover sites, suggesting that abundant Ranunculus reduced interspecific competition. This field experiment shows that high Ranunculus cover can support more and better growing juvenile salmon, and facilitate foraging and co-existence of sympatric salmonid species. Maintaining or enhancing natural macrophyte cover can be achieved through sympathetic in-river and riparian vegetation management and mitigating pressures on them, such as sediment inputs and low flows, or through planting. Further research should test whether macrophyte cover benefits propagate to subsequent life stages, particularly juvenile overwintering associated with high mortality. This knowledge, in combination with our findings, would further clarify whether beneficial juvenile habitat can improve the viability of at-risk salmonid populations. Overall, our findings suggest that the aims of river restoration might be achieved through promotion of in-stream aquatic vegetation.
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Salmo salar , Animales , Agua Dulce , Ríos , Estaciones del Año , TruchaRESUMEN
BACKGROUND AND AIM: Portal vein thrombosis (PVT) is a common complication of cirrhosis. The exact pathophysiology remains largely unknown, and treatment with anticoagulants does not lead to recanalization of the portal vein in all patients. A better insight into the structure and composition of portal vein thrombi may assist in developing strategies for the prevention and treatment of PVT. APPROACH AND RESULTS: Sixteen prospectively and 63 retrospectively collected nonmalignant portal vein thrombi from patients with cirrhosis who underwent liver transplantation were included. Histology, immunohistochemistry, and scanning electron microscopy were used to assess structure and composition of the thrombi. Most recent CT scans were reanalyzed for thrombus characteristics. Clinical characteristics were related to histological and radiological findings. All samples showed a thickened, fibrotic tunica intima. Fibrin-rich thrombi were present on top of the fibrotic intima in 9/16 prospective cases and in 21/63 retrospective cases. A minority of the fibrotic areas stained focally positive for fibrin/fibrinogen (16% of cases), von Willebrand factor (VWF; 10%), and CD61 (platelets, 21%), while most of the fibrin-rich areas stained positive for those markers (fibrin/fibrinogen, 100%; VWF, 77%; CD61, 100%). No associations were found between clinical characteristics including estimated thrombus age and use of anticoagulants and presence of fibrin-rich thrombi. CONCLUSION: We demonstrate that PVT in patients with cirrhosis consists of intimal fibrosis with an additional fibrin-rich thrombus in only one-third of cases. We hypothesize that our observations may explain why not all portal vein thrombi in patients with cirrhosis recanalize by anticoagulant therapy.
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Trombosis , Trombosis de la Vena , Anticoagulantes/uso terapéutico , Fibrina/uso terapéutico , Fibrinógeno , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Vena Porta , Estudios Retrospectivos , Trombosis/etiología , Trombosis de la Vena/complicaciones , Factor de von WillebrandRESUMEN
BACKGROUND: Re-irradiation (reRT) is a promising technique for patients with localized recurrence in a previously irradiated area but presents major challenges. These include how to deal with anatomical change between two courses of radiotherapy and integration of radiobiology when summating original and re-irradiation doses. The Support Tool for Re-Irradiation Decisions guided by Radiobiology (STRIDeR) project aims to develop a software tool for use in a commercial treatment planning system to facilitate more informed reRT by accounting for anatomical changes and incorporating radiobiology. We evaluated three approaches to dose summation, incorporating anatomical change and radiobiology to differing extents. METHODS: In a cohort of 21 patients who previously received pelvic re-irradiation the following dose summation strategies were compared: (1) Rigid registration (RIR) and physical dose summation, to reflect the current clinical approach, (2) RIR and radiobiological dose summation in equivalent dose in 2 Gy fractions (EQD2), and (3) Patient-specific deformable image registration (DIR) with EQD2 dose summation. RESULTS: RIR and physical dose summation (Strategy 1) resulted in high cumulative organ at risk (OAR) doses being 'missed' in 14% of cases, which were highlighted by EQD2 dose summation (Strategy 2). DIR (with EQD2 dose summation; Strategy 3) resulted in improved OAR overlap and distance to agreement metrics compared to RIR (with EQD2 dose summation; Strategy 2) and was consistently preferred in terms of clinical utility. DIR was considered to have a clinically important impact on dose summation in 38% of cases. CONCLUSION: Re-irradiation cases require individualized assessment when considering dose summation with the previous treatment plan. Fractionation correction is necessary to meaningfully assess cumulative doses and reduce the risk of unintentional OAR overdose. DIR can add clinically relevant information in selected cases, especially for significant anatomical change. Robust solutions for cumulative dose assessment offer the potential for future improved understanding of cumulative OAR tolerances.
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Reirradiación , Fraccionamiento de la Dosis de Radiación , Humanos , Pelvis , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por ComputadorRESUMEN
Pancreatic neuroendocrine tumours can have varied and complex presentations. Whilst hormone hypersecretion often induces characteristic clinical syndromes, non-specific symptoms may arise due to localized tumour effects. Malignant invasion of local vasculature is an increasingly recognized complication of these neoplasms and can be associated with significant morbidity. Herein, we present the case of a 47-year-old male with a recurrence of a pancreatic neuroendocrine tumour who presented with unusual upper gastrointestinal bleeding. The tumour had recurred within the superior mesenteric vein, replacing the vessel and invading its branches. This resulted in porto-mesenteric hypertension and the formation of bleeding mesenteric varices. The patient subsequently developed progressive metabolic disturbances and was diagnosed with ectopic Cushing's syndrome, despite his primary tumour having been non-functional. This case demonstrates not only a rare pattern of tumour recurrence but also the potential for pancreatic neuroendocrine tumours to de-differentiate and change from non-functional to hormone secreting, a phenomenon which may complicate diagnosis and management.