Stable isotope-based methods have proved to be immensely valuable for ecological studies ranging in focus from animal movements to species interactions and community structure. Nevertheless, the use ...of these methods is dependent on assumptions about the incorporation and turnover of isotopes within animal tissues, which are oftentimes not explicitly acknowledged and vetted. Thus, the purpose of this review is to provide an overview of the estimation of stable isotope turnover rates in animals, and to highlight the importance of these estimates for ecological studies in terrestrial, freshwater, and marine systems that may use a wide range of stable isotopes. Specifically, we discuss 1) the factors that contribute to variation in turnover among individuals and across species, which influences the use of stable isotopes for diet reconstructions, 2) the differences in turnover among tissues that underlie so-called ‘isotopic clocks’, which are used to estimate the timing of dietary shifts, and 3) the use of turnover rates to estimate nutritional requirements and reconstruct histories of nutritional stress from tissue isotope signatures. As we discuss these topics, we highlight recent works that have effectively used estimates of turnover to design and execute informative ecological studies. Our concluding remarks suggest several steps that will improve our understanding of isotopic turnover and support its integration into a wider range of ecological studies.
Whether dietary antioxidants are effective for alleviating oxidative costs associated with energy-demanding life events first requires they are successfully absorbed in the digestive tract and ...transported to sites associated with reactive species production (e.g. the mitochondria). Flying birds are under high energy and oxidative demands, and although birds commonly ingest dietary antioxidants in the wild, the bioavailability of these consumed antioxidants is poorly understood. We show for the first time that an ingested lipophilic antioxidant, α-tocopherol, reached the mitochondria in the flight muscles of a songbird but only if they regularly exercise (60 min of perch-to-perch flights two times in a day or 8.5 km day-1). Deuterated α-tocopherol was found in the blood of exercise-trained zebra finches within 6.5 hrs and in isolated mitochondria from pectoral muscle within 22.5 hrs, but never reached the mitochondria in caged sedentary control birds. This rapid pace (within a day) and extent of metabolic routing of a dietary antioxidant to muscle mitochondria means that daily consumption of such dietary sources can help to pay the inevitable oxidative costs of flight muscle metabolism, but only when combined with regular exercise.
The noble gases are elements of broad importance across science and technology and are primary constituents of planetary and stellar atmospheres, where they segregate into droplets or layers that ...affect the thermal, chemical, and structural evolution of their host body. We have measured the optical properties of noble gases at relevant high pressures and temperatures in the laser-heated diamond anvil cell, observing insulator-to-conductor transformations in dense helium, neon, argon, and xenon at 4,000â15,000 K and pressures of 15â52 GPa. The thermal activation and frequency dependence of conduction reveal an optical character dominated by electrons of low mobility, as in an amorphous semiconductor or poor metal, rather than free electrons as is often assumed for such wide band gap insulators at high temperatures. White dwarf stars having helium outer atmospheres cool slower and may have different color than if atmospheric opacity were controlled by free electrons. Helium rain in Jupiter and Saturn becomes conducting at conditions well correlated with its increased solubility in metallic hydrogen, whereas a deep layer of insulating neon may inhibit core erosion in Saturn.
Significance Planets and stars contain matter at extreme pressures and temperatures hidden deep beneath their opaque surfaces. Unable to see these states of matter directly, we instead produce them in laboratory experiments. Here a novel method of studying extreme states in a tabletop experiment is described and applied to common planet- and star-forming materials, the noble gases. Helium, neon, argon, and xenon transform in the experiments from transparent electrical insulators to opaque electrical conductors. In Saturn, rain composed of noble gas becomes conductive as it falls and can form a protective layer around the planetary core that prevents the core from dissolving into surrounding metallic hydrogen. White dwarf stars have unexpectedly opaque helium atmospheres, causing them to age slower than anticipated.
Collateralisation around stenotic or occlusive arterial disease is a commonly observed adaptation for maintenance of arterial perfusion. It occurs through pathways of well-understood embryological ...origin. Examples include Winslow's pathway (internal thoracic artery to iliac artery via the epigastric arteries) and the arc of Riolan (between superior and inferior mesenteric arteries). In this article, we describe a pathway of collateralisation around stenotic disease of the coeliac and superior mesenteric arteries in a 76-year-old man with an abdominal aortic aneurysm. The collateral pathway was identified on computed tomography angiography between the left internal thoracic artery in the thorax and the coeliac artery in the abdomen via the left inferior phrenic artery. This has implications for routine cardiac surgery, such that left internal thoracic artery harvest during coronary artery bypass surgery would likely result in acute ischaemia of the abdominal viscera.
To assess the improvements during patient follow-up after implementing a proactive plan for retrieval of inferior vena cava (IVC) filters.
A retrospective study was undertaken including all patients ...who had a temporary IVC filter inserted over a 10-year period. Patient demographics, insertion dates, retrieval dates, retrieval rates, and complications were recorded. Patients were categorised into three groups as follows: group A, no intervention where retrieval was not suggested; group B, passive intervention where retrieval was suggested but no appointment made; and group C, proactive intervention where a retrieval date was booked by the radiologist.
Five hundred and nine patients had a temporary IVC filter inserted at Royal Liverpool University Hospital over the study period. One per cent of patients in group C were lost to follow-up compared to 41% and 29% in groups A and B respectively (p<0.001). The number of patients who had an IVC retrieval attempt also increased to 80% in group C compared to 53% and 64% in groups A and B (p<0.001).
Incorporation of a proactive retrieval booking system has significantly reduced the number of patients lost to follow-up to 1%, leading to an increased number of IVC filter retrieval attempts.
•Inferior Vena Cava filter (IVCF) retrieval rates remain poor.•Active retrieval plan introduced to reduce lost to follow-up rate.•Automatic retrieval appointments generated immediately after IVCF insertion.•Plan reduces lost to follow-up rate and increases number of retrieval attempts.
CDKN2A and TP53 mutations are recurrent events in melanoma, occurring in 13.3% and 15.1% of cases respectively and are associated with poorer outcomes. It is unclear what effect CDKN2A and TP53 ...mutations have on the clinical outcomes of patients treated with checkpoint inhibitors.
All patients with cutaneous melanoma or melanoma of unknown primary who received checkpoint inhibitor therapy and underwent genomic profiling with the 50-gene Mayo Clinic solid tumor targeted cancer gene panel were included. Patients were stratified according to the presence or absence of mutations in BRAF, NRAS, CDKN2A, and TP53. Patients without mutations in any of these genes were termed quadruple wild type (QuadWT). Clinical outcomes including median time to progression (TTP), median overall survival (OS), 6-month and 12-month OS, 6-month and 12-month without progression, ORR and disease control rate (DCR) were analyzed according to the mutational status of CDKN2A, TP53 and QuadWT.
A total of 102 patients were included in this study of which 14 had mutations of CDKN2A (CDKN2Amut), 21 had TP53 mutations (TP53mut), and 12 were QuadWT. TP53mut, CDKN2Amut and QuadWT mutational status did not impact clinical outcomes including median TTP, median OS, 6-month and 12-month OS, 6-month and 12-month without progression, ORR and DCR. There was a trend towards improved median TTP and DCR in CDKN2Amut cohort and a trend towards worsened median TTP in the QuadWT cohort.
Cell cycle regulators such as TP53 and CDKN2A do not appear to significantly alter clinical outcomes when immune checkpoint inhibitors are used.
Bismuth has long been a prototypical system for investigating phase transformations and melting at high pressure. Despite decades of experimental study, however, the lattice-level response of Bi to ...rapid (shock) compression and the relationship between structures occurring dynamically and those observed during slow (static) compression, are still not clearly understood. We have determined the structural response of shock-compressed Bi to 68 GPa using femtosecond X-ray diffraction, thereby revealing the phase transition sequence and equation-of-state in unprecedented detail for the first time. We show that shocked-Bi exhibits a marked departure from equilibrium behavior - the incommensurate Bi-III phase is not observed, but rather a new metastable phase, and the Bi-V phase is formed at significantly lower pressures compared to static compression studies. We also directly measure structural changes in a shocked liquid for the first time. These observations reveal new behaviour in the solid and liquid phases of a shocked material and give important insights into the validity of comparing static and dynamic datasets.
Background
Fenestrated endovascular aneurysm repair (FEVAR) is increasingly being used for juxtarenal aortic aneurysms. The aim of this study was to review long‐term results and assess the importance ...of changing stent‐graft design on outcomes.
Methods
This was a retrospective review of all patients who underwent FEVAR within a single unit over 12 years (February 2003 to December 2015). Kaplan–Meier analysis of survival, and freedom from target vessel loss, aneurysm expansion, graft‐related endoleak and secondary intervention was performed. Comparison between outcomes of less complex grafts (fewer than 3 fenestrations) and more complex grafts (3 or 4 fenestrations) was undertaken.
Results
Some 173 patients underwent FEVAR; median age was 76 (i.q.r. 70–79) years and 90·2 per cent were men. Median aneurysm diameter was 63 (59–71) mm and median follow‐up was 34 (16–50) months. The adjusted primary technical operative success rate was 95·4 per cent. The in‐hospital mortality rate was 5·2 per cent; there was no known aneurysm‐related death during follow‐up. Median survival was 7·1 (95 per cent c.i. 5·2 to 8·1) years and overall survival was 60·1 per cent (104 of 173). There was a trend towards an increasing number of fenestrations in the graft design over time. In‐hospital mortality appeared higher when more complex stent‐grafts were used (8 versus 2 per cent for stent‐grafts with 3–4 versus fewer than 3 fenestrations; P = 0·059). Graft‐related endoleaks were more common following deployment of stent‐grafts with three or four fenestrations (12 of 90 versus 6 of 83; P < 0·001).
Conclusion
Fenestrated endovascular aneurysm repair for juxtarenal aneurysm is associated with few aneurysm‐related deaths in the long term. Significant numbers of secondary interventions are required, but the majority of these can be performed using an endovascular approach.
Prevents aneurysm rupture
Brain AVM, cerebral abscess, and ischemic stroke are among the well known neurologic manifestations of hereditary hemorrhagic telangiectasia. However, recently reported data suggest an additional ...association with malformations of cortical development. The purpose of this study was to determine the prevalence of malformations of cortical development in a population of pediatric patients with hereditary hemorrhagic telangiectasia.
A retrospective review of brain MRIs from 116 pediatric patients was performed. Each patient was referred from our institution's Hereditary Hemorrhagic Telangiectasia Clinic. Each MRI included a 3D sequence, most frequently MPRAGE. The 3D sequence was evaluated by a neuroradiology fellow, with specific attention to the presence or absence of malformations of cortical development. Positive studies were subsequently reviewed by 2 attending neuroradiologists, who rendered a final diagnosis.
Fourteen of 116 (12.1%) patients were found to have a malformation of cortical development. Among these 14, there were 12 cases of polymicrogyria and 2 cases of bifrontal periventricular nodular heterotopia.
Pediatric patients with hereditary hemorrhagic telangiectasia have a relatively high prevalence of malformations of cortical development, typically perisylvian polymicrogyria.
Uveal melanoma is a rare type of melanoma, with only five to seven cases per one million persons diagnosed each year. Patients with metastatic melanoma of uveal origin tend to have lower response ...rates on traditional therapies. Herein we report our experience with 10 patients with metastatic uveal melanoma (MUM) who received pembrolizumab. Eligible patients were more than or equal to 18 years old, had unresectable MUM, progressed on prior ipilimumab therapy, had good performance status (Eastern Cooperative Oncology Group of 0 or 1), and adequate organ and marrow function. Patients could have central nervous system disease, but needed to be clinically stable. Patients were treated with 2 mg/kg pembrolizumab intravenously over 30 min every 3 weeks until disease progression, unacceptable toxicity, or for up to 2 years. Between April 2014 and October 2014, we treated a total of 10 patients with MUM with pembrolizumab. Median age was 65 years, with 70% being female. As of the data cutoff date of 14 May 2015, median progression-free survival was 18 weeks (range 3.14-49.3 weeks), with four patients still currently receiving therapy. Of eight evaluable patients, there was one complete response, two partial responses, and one patient with stable disease. Four patients had rapidly progressive disease. Toxicities were as expected and were usually grade 1/2 in nature. Although this cohort of patients was small, to our knowledge this is the first such report of outcomes in uveal melanoma patients being treated with anti-PD1 therapy. In the absence of a clinical trial, treatment with pembrolizumab appears to be a viable option for patients with MUM.
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