Keeping cool in acute liver failure: rationale for the use of mild hypothermia

Encephalopathy, brain edema and intracranial hypertension are neurological complications responsible for substantial morbidity/mortality in patients with acute liver failure (ALF), where, aside from liver transplantation, there is currently a paucity of effective therapies. Mirroring its cerebro-protective effects in other clinical conditions, the induction of mild hypothermia may provide a potential therapeutic approach to the management of ALF. A solid mechanistic rationale for the use of mild hypothermia is provided by clinical and experimental studies showing its beneficial effects in relation to many of the key factors that determine the development of brain edema and intracranial hypertension in ALF, namely the delivery of ammonia to the brain, the disturbances of brain organic osmolytes and brain extracellular amino acids, cerebro-vascular haemodynamics, brain glucose metabolism, inflammation, subclinical seizure activity and alterations of gene expression. Initial uncontrolled clinical studies of mild hypothermia in patients with ALF suggest that it is an effective, feasible and safe approach. Randomized controlled clinical trials are now needed to adequately assess its efficacy, safety, clinical impact on global outcomes and to provide the guidelines for its use in ALF.CR: CIHR-post-doctoral fellowshi

Breakfast and exercise contingently affect postprandial metabolism and energy balance in physically active males

The present study examined the impact of breakfast and exercise on postprandial metabolism, appetite and macronutrient balance. A sample of twelve (blood variables n 11) physically active males completed four trials in a randomised, crossover design comprising a continued overnight fast followed by: (1) rest without breakfast (FR); (2) exercise without breakfast (FE); (3) breakfast consumption(1859 kJ) followed by rest (BR); (4) breakfast consumption followed by exercise (BE). Exercise was continuous, moderate-intensity running (expending approximately 2·9MJ of energy). The equivalent time was spent sitting during resting trials. A test drink (1500 kJ) was ingested on all trials followed 90 min later by an ad libitum lunch. The difference between the BR and FR trials in blood glucose time-averaged AUC following test drink consumption approached significance (BR: 4·33 (SEM 0·14) v. FR: 4·75 (SEM 0·16) mmol/l; P¼0·08); but it was not different between FR and FE (FE: 4·77 (SEM 0·14) mmol/l; P¼0·65); and was greater in BE (BE: 4·97 (SEM 0·13) mmol/l) v. BR(P¼0·012). Appetite following the test drink was reduced in BR v. FR (P¼0·006) and in BE v. FE (P¼0·029). Following lunch, the most positive energy balance was observed in BR and least positive in FE. Regardless of breakfast, acute exercise produced a less positive energy balance following ad libitum lunch consumption. Energy and fat balance is further reduced with breakfast omission. Breakfast improved the overall appetite responses to foods consumed later in the day, but abrogated the appetite suppressive effect of exercise

Bottom-up control of sardine and anchovy population cycles in the canary current: insights from an end-to-end model simulation

Sardine and anchovy can exhibit dramatic decadal-scale shifts in abundance in response to climate variability. Sharpe declines of these populations entail particularly serious commercial and ecological consequences in eastern boundary current ecosystems, where they sustain major world fisheries and provide the forage for a broad variety of predators. Understanding the mechanisms and environmental forcing that drive the observed fish variability remains a challenging problem. The modelling study presented here provides an approach that bridges a comprehensive database with an end-to-end modelling framework enabling the investigation of the sources of variability of sardine and anchovy in the Canary Current System. Different biological traits and behaviour prescribed for sardine and anchovy gave rise to different distribution and displacements of the populations, but to a rather synchronous variability in terms of abundance and biomass, in qualitative agreement with historical landing records. Analysis of years with anomalously high increase and decline of the adult population points to food availability (instead of temperature or other environmental drivers) as the main environmental factor determining recruitment for both sardine (via spawning and survival of feeding age-0 individuals) and anchovy (via survival of feeding age-0). Consistent with this, the two species thrive under enhanced upwelling-favourable winds, but only up to some threshold of the wind velocity beyond which larval drift mortality exceeds the positive effect of the extra food supply. Based on the analysis of the simulation, we found that anchovy larvae are particularly vulnerable to enhanced wind-driven advection, and as such do better with more moderate upwelling than sardines.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Long‐term nutrient addition increases respiration and nitrous oxide emissions in a New England salt marsh

© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Ecology and Evolution 8 (2018): 4958-4966, doi:10.1002/ece3.3955.Salt marshes may act either as greenhouse gas (GHG) sources or sinks depending on hydrological conditions, vegetation communities, and nutrient availability. In recent decades, eutrophication has emerged as a major driver of change in salt marsh ecosystems. An ongoing fertilization experiment at the Great Sippewissett Marsh (Cape Cod, USA) allows for observation of the results of over four decades of nutrient addition. Here, nutrient enrichment stimulated changes to vegetation communities that, over time, have resulted in increased elevation of the marsh platform. In this study, we measured fluxes of carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O) in dominant vegetation zones along elevation gradients of chronically fertilized (1,572 kg N ha−1 year−1) and unfertilized (12 kg N ha−1 year−1) experimental plots at Great Sippewissett Marsh. Flux measurements were performed using darkened chambers to focus on community respiration and excluded photosynthetic CO2 uptake. We hypothesized that N‐replete conditions in fertilized plots would result in larger N2O emissions relative to control plots and that higher elevations caused by nutrient enrichment would support increased CO2 and N2O and decreased CH4 emissions due to the potential for more oxygen diffusion into sediment. Patterns of GHG emission supported our hypotheses. Fertilized plots were substantially larger sources of N2O and had higher community respiration rates relative to control plots, due to large emissions of these GHGs at higher elevations. While CH4 emissions displayed a negative relationship with elevation, they were generally small across elevation gradients and nutrient enrichment treatments. Our results demonstrate that at decadal scales, vegetation community shifts and associated elevation changes driven by chronic eutrophication affect GHG emission from salt marshes. Results demonstrate the necessity of long‐term fertilization experiments to understand impacts of eutrophication on ecosystem function and have implications for how chronic eutrophication may impact the role that salt marshes play in sequestering C and N

Calculating the Sun\u27s Photospheric Temperature, an Undergraduate Physics Laboratory

We provide physics students and teachers with a simple technique for measuring the solar spectrum and a method for analyzing that spectrum through popular computer software. We discuss modern physics concepts related to blackbody radiation while modeling the sun\u27s spectrum to determine the temperature of the sun\u27s photosphere. We provide a reliable method to determine the sun\u27s photospheric temperature with a typical error of less than 10%, primarily dependent on atmospheric conditions. The focus of this work is on data analysis, not acquisition

Physical consequences of P≠\neqNP and the DMRG-annealing conjecture

Computational complexity theory contains a corpus of theorems and conjectures regarding the time a Turing machine will need to solve certain types of problems as a function of the input size. Nature {\em need not} be a Turing machine and, thus, these theorems do not apply directly to it. But {\em classical simulations} of physical processes are programs running on Turing machines and, as such, are subject to them. In this work, computational complexity theory is applied to classical simulations of systems performing an adiabatic quantum computation (AQC), based on an annealed extension of the density matrix renormalization group (DMRG). We conjecture that the computational time required for those classical simulations is controlled solely by the {\em maximal entanglement} found during the process. Thus, lower bounds on the growth of entanglement with the system size can be provided. In some cases, quantum phase transitions can be predicted to take place in certain inhomogeneous systems. Concretely, physical conclusions are drawn from the assumption that the complexity classes {\bf P} and {\bf NP} differ. As a by-product, an alternative measure of entanglement is proposed which, via Chebyshev's inequality, allows to establish strict bounds on the required computational time.Comment: Accepted for publication in JSTA

The role of temperature in the magnetic irreversibility of type-I Pb superconductors

Evidence of how temperature takes part in the magnetic irreversibility in the intermediate state of a cylinder and various disks of pure type-I superconducting lead is presented. Isothermal measurements of first magnetization curves and magnetic hysteresis cycles are analyzed in a reduced representation that defines an equilibrium state for flux penetration in all the samples and reveals that flux expulsion depends on temperature in the disks but not in the cylinder. The magnetic field at which irreversibility sets in along the descending branch of the hysteresis cycle and the remnant magnetization at zero field are found to decrease with temperature in the disks. The contributions to irreversibility of the geometrical barrier and the energy minima associated to stress defects that act as pinning centers on normal-superconductor interfaces are discussed. The differences observed among the disks are ascribed to the diverse nature of the stress defects in each sample. The pinning barriers are suggested to decrease with the magnetic field to account for these results

Improved high throughput protocol for targeting eukaryotic symbionts in metazoan and eDNA samples

Eukaryote symbionts of animals are major drivers of ecosystems not only because of their diversity and host interactions from variable pathogenicity but also through different key roles such as commensalism and to different types of interdependence. However, molecular investigations of metazoan eukaryomes require minimising coamplification of homologous host genes. In this study we (1) identified a previously published “antimetazoan” reverse primer to theoretically enable amplification of a wider range of microeukaryotic symbionts, including more evolutionarily divergent sequence types, (2) evaluated in silico several antimetazoan primer combinations, and (3) optimised the application of the best performing primer pair for high throughput sequencing (HTS) by comparing one-step and two-step PCR amplification approaches, testing different annealing temperatures and evaluating the taxonomic profiles produced by HTS and data analysis. The primer combination 574*F – UNonMet_DB tested in silico showed the largest diversity of nonmetazoan sequence types in the SILVA database and was also the shortest available primer combination for broadly-targeting antimetazoan amplification across the 18S rRNA gene V4 region. We demonstrate that the one-step PCR approach used for library preparation produces significantly lower proportions of metazoan reads, and a more comprehensive coverage of host-associated microeukaryote reads than the two-step approach. Using higher PCR annealing temperatures further increased the proportion of nonmetazoan reads in all sample types tested. The resulting V4 region amplicons were taxonomically informative even when only the forward read is analysed. This region also revealed a diversity of known and putatively parasitic lineages and a wider diversity of host-associated eukaryotes.publishedVersio

Serological screening for tick-borne encephalitis virus in eight Norwegian herds of semi-domesticated reindeer

Tick-borne encephalitis virus (TBEV) is found in Ixodes ricinus ticks throughout the area where viable tick populations exist. In Norway, TBEV is found in I. ricinus from the south coast until Brønnøy municipality in Nordland County and the range of the vector is expanding due to changes in climate, vegetation, host animals and environmental conditions. TBEV might thus have the potential to establish in new areas when I. ricinus expand its geographical distribution. At present, there is little knowledge on the status of the virus in high-altitude areas of inland regions in Norway. It has previously been indicated that reindeer may be an important sentinel species and indicator of the spread of ticks and TBEV in high-altitude regions. In this study, 408 semi-domesticated Eurasian tundra reindeer (Rangifer tarandus tarandus) from eight herds, from Tana in Troms and Finnmark County in northern Norway to Filefjell in Innlandet and Viken Counties in southern Norway, were screened for TBEV antibodies using a commercial enzyme-linked immunosorbent assay (ELISA). We found 16 TBEV reactive reindeer samples by ELISA; however, these results could not be confirmed by the serum neutralization test (SNT). This could indicate that a flavivirusand not necessarily TBEV, may be circulating among Norwegian semi-domesticated reindeer. The results also indicate that TBEV was not enzootic in Norwegian semi-domesticated reindeer in 2013–2015. This knowledge is important as an information base for future TBEV and flavivirus surveillance in Norway

Radiofluorination of a highly potent ATM inhibitor as a potential PET imaging agent

PURPOSE: Ataxia telangiectasia mutated (ATM) is a key mediator of the DNA damage response, and several ATM inhibitors (ATMi) are currently undergoing early phase clinical trials for the treatment of cancer. A radiolabelled ATMi to determine drug pharmacokinetics could assist patient selection in a move towards more personalised medicine. The aim of this study was to synthesise and investigate the first 18F-labelled ATM inhibitor [18F]1 for non-invasive imaging of ATM protein and ATMi pharmacokinetics. METHODS: Radiofluorination of a confirmed selective ATM inhibitor (1) was achieved through substitution of a nitro-precursor with [18F]fluoride. Uptake of [18F]1 was assessed in vitro in H1299 lung cancer cells stably transfected with shRNA to reduce expression of ATM. Blocking studies using several non-radioactive ATM inhibitors assessed binding specificity to ATM. In vivo biodistribution studies were performed in wild-type and ATM-knockout C57BL/6 mice using PET/CT and ex vivo analysis. Uptake of [18F]1 in H1299 tumour xenografts was assessed in BALB/c nu/nu mice. RESULTS: Nitro-precursor 2 was synthesised with an overall yield of 12%. Radiofluorination of 2 achieved radiochemically pure [18F]1 in 80 ± 13 min with a radiochemical yield of 20 ± 13% (decay-corrected) and molar activities up to 79.5 GBq/μmol (n = 11). In vitro, cell-associated activity of [18F]1 increased over 1 h, and retention of [18F]1 dropped to 50% over 2 h. [18F]1 uptake did not correlate with ATM expression, but could be reduced significantly with an excess of known ATM inhibitors, demonstrating specific binding of [18F]1 to ATM. In vivo, fast hepatobiliary clearance was observed with tumour uptake ranging 0.13-0.90%ID/g after 1 h. CONCLUSION: Here, we report the first radiofluorination of an ATM inhibitor and its in vitro and in vivo biological evaluations, revealing the benefits but also some limitations of 18F-labelled ATM inhibitors