Safety of selective internal radiation therapy (SIRT) with yttrium-90 microspheres combined with systemic anticancer agents: expert consensus

Selective internal radiation therapy (SIRT) with microspheres labelled with the β-emitter yttrium-90 (Y-90) enables targeted delivery of radiation to hepatic tumors. SIRT is primarily used to treat inoperable primary or metastatic liver tumors. Eligible patients have usually been exposed to a variety of systemic anticancer therapies, including cytotoxic agents, targeted biologics, immunotherapy and peptide receptor radionuclide therapy (PRRT). All these treatments have potential interactions with SIRT; however, robust evidence on the safety of these potential combinations is lacking. This paper provides current clinical experiences and expert consensus guidelines for the use of SIRT in combination with the anticancer treatment agents likely to be encountered in clinical practice. It was agreed by the expert panel that precautions need to be taken with certain drugs, but that, in general, systemic therapies do not necessarily have to be stopped to perform SIRT. The authors recommend stopping vascular endothelial growth factor inhibitors 4-6 weeks before SIRT, and restart after the patient has recovered from the procedure. It may also be prudent to stop potent radiosensitizers such as gemcitabine therapy 4 weeks before SIRT, and restart treatment at least 2‒4 weeks later. Data from phase III studies combining SIRT with fluorouracil (5FU) or folinic acid/5FU/oxaliplatin (FOLFOX) suggest that hematological toxicity is more common from the combination than it is from chemotherapy without SIRT. There is no evidence to suggest that chemotherapy increases SIRT-specific gastro-intestinal or liver toxicities

Giant Superfluorescent Bursts from a Semiconductor Magnetoplasma

Currently, considerable resurgent interest exists in the concept of superradiance (SR), i.e., accelerated relaxation of excited dipoles due to cooperative spontaneous emission, first proposed by Dicke in 1954. Recent authors have discussed SR in diverse contexts, including cavity quantum electrodynamics, quantum phase transitions, and plasmonics. At the heart of these various experiments lies the coherent coupling of constituent particles to each other via their radiation field that cooperatively governs the dynamics of the whole system. In the most exciting form of SR, called superfluorescence (SF), macroscopic coherence spontaneously builds up out of an initially incoherent ensemble of excited dipoles and then decays abruptly. Here, we demonstrate the emergence of this photon-mediated, cooperative, many-body state in a very unlikely system: an ultradense electron-hole plasma in a semiconductor. We observe intense, delayed pulses, or bursts, of coherent radiation from highly photo-excited semiconductor quantum wells with a concomitant sudden decrease in population from total inversion to zero. Unlike previously reported SF in atomic and molecular systems that occur on nanosecond time scales, these intense SF bursts have picosecond pulse-widths and are delayed in time by tens of picoseconds with respect to the excitation pulse. They appear only at sufficiently high excitation powers and magnetic fields and sufficiently low temperatures - where various interactions causing decoherence are suppressed. We present theoretical simulations based on the relaxation and recombination dynamics of ultrahigh-density electron-hole pairs in a quantizing magnetic field, which successfully capture the salient features of the experimental observations.Comment: 21 pages, 4 figure

Hybridization in parasites: consequences for adaptive evolution, pathogenesis and public health in a changing world

[No abstract available

The comparative osmoregulatory ability of two water beetle genera whose species span the fresh-hypersaline gradient in inland waters (Coleoptera: Dytiscidae, Hydrophilidae).

A better knowledge of the physiological basis of salinity tolerance is essential to understanding the ecology and evolutionary history of organisms that have colonized inland saline waters. Coleoptera are amongst the most diverse macroinvertebrates in inland waters, including saline habitats; however, the osmoregulatory strategies they employ to deal with osmotic stress remain unexplored. Survival and haemolymph osmotic concentration at different salinities were examined in adults of eight aquatic beetle species which inhabit different parts of the fresh-hypersaline gradient. Studied species belong to two unrelated genera which have invaded saline waters independently from freshwater ancestors; Nebrioporus (Dytiscidae) and Enochrus (Hydrophilidae). Their osmoregulatory strategy (osmoconformity or osmoregulation) was identified and osmotic capacity (the osmotic gradient between the animal's haemolymph and the external medium) was compared between species pairs co-habiting similar salinities in nature. We show that osmoregulatory capacity, rather than osmoconformity, has evolved independently in these different lineages. All species hyperegulated their haemolymph osmotic concentration in diluted waters; those living in fresh or low-salinity waters were unable to hyporegulate and survive in hyperosmotic media (> 340 mosmol kg(-1)). In contrast, the species which inhabit the hypo-hypersaline habitats were effective hyporegulators, maintaining their haemolymph osmolality within narrow limits (ca. 300 mosmol kg(-1)) across a wide range of external concentrations. The hypersaline species N. ceresyi and E. jesusarribasi tolerated conductivities up to 140 and 180 mS cm(-1), respectively, and maintained osmotic gradients over 3500 mosmol kg(-1), comparable to those of the most effective insect osmoregulators known to date. Syntopic species of both genera showed similar osmotic capacities and in general, osmotic responses correlated well with upper salinity levels occupied by individual species in nature. Therefore, osmoregulatory capacity may mediate habitat segregation amongst congeners across the salinity gradient

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Acute Cellular Alterations in the Hippocampus After Status Epilepticus

The critical, fundamental mechanisms that determine the emergence of status epilepticus from a single seizure and the prolonged duration of status epilepticus are uncertain. However, several general concepts of the pathophysiology of status epilepticus have emerged: (a) the hippocampus is consistently activated during status epilepticus; (b) loss of GABA-mediated inhibitory synaptic transmission in the hippocampus is critical for emergence of status epilepticus; and, finally (c) glutamatergic excitatory synaptic transmission is important in sustaining status epilepticus. This review focuses on the alteration of GABAergic inhibition in the hippocampus that occurs during the prolonged seizures of status epilepticus. If reduction in GABAergic inhibition leads to development of status epilepticus, enhancement of GABAergic inhibition would be expected to interrupt status epilepticus. Benzodiazepines and barbiturates are both used in the treatment of status epilepticus and both drugs enhance GABA A receptor-mediated inhibition. However, patients often become refractory to benzodiazepines when seizures are prolonged, and barbiturates are often then used for these refractory cases of status epilepticus. Recent evidence suggests the presence of multiple GABA A receptor isoforms in the hippocampus with different sensitivity to benzodiazepines but similar sensitivity to barbiturates, thus explaining why the two drug classes might have different clinical effects. In addition, rapid functional plasticity of GABA A receptors has been demonstrated to occur during status epilepticus in rats. During status epilepticus, there was a substantial reduction of diazepam potency for termination of the seizures. The loss of sensitivity of the animals to diazepam during status epilepticus was accompanied by an alteration in the functional properties of hippocampal dentate granule cell GABA A receptors. Dentate granule cell GABA A receptor currents from rats undergoing status epilepticus had reduced sensitivity to diazepam and zinc but normal sensitivity to GABA and pentobarbital. Therefore, the prolonged seizures of status epilepticus rapidly altered the functional properties of hippocampal dentate granule cell GABA A receptors, possibly explaining why benzodiazepines and barbiturates may not be equally effective during treatment of the prolonged seizures of status epilepticus. A comprehensive understanding of the cellular and molecular events leading to the development, maintenance, and cytotoxicity of status epilepticus should permit development of more effective treatment strategies and reduction in the mortality and morbidity of status epilepticus.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65664/1/j.1528-1157.1999.tb00873.x.pd

Pervasive transition of the Brazilian land-use system

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Contrasting effects of hemiparasites on ecosystem processes: can positive litter effects offset the negative effects of parasitism?

Hemiparasites are known to influence community structure and ecosystem functioning, but the underlying mechanisms are not well studied. Variation in the impacts of hemiparasites on diversity and production could be due to the difference in the relative strength of two interacting pathways: direct negative effects of parasitism and positive effects on N availability via litter. Strong effects of parasitism should result in substantial changes in diversity and declines in productivity. Conversely, strong litter effects should result in minor changes in diversity and increased productivity. We conducted field-based surveys to determine the association of Castillejaoccidentalis with diversity and productivity in the alpine tundra. To examine litter effects, we compared the decomposition of Castilleja litter with litter of four other abundant plant species, and examined the decomposition of those four species when mixed with Castilleja. Castilleja was associated with minor changes in diversity but almost a twofold increase in productivity and greater foliar N in co-occurring species. Our decomposition trials suggest litter effects are due to both the rapid N loss of Castilleja litter and the effects of mixing Castilleja litter with co-occurring species. Castilleja produces litter that accelerates decomposition in the alpine tundra, which could accelerate the slow N cycle and boost productivity. We speculate that these positive effects of litter outweigh the effects of parasitism in nutrient-poor systems with long-lived hemiparasites. Determining the relative importance of parasitism and litter effects of this functional group is crucial to understand the strong but variable roles hemiparasites play in affecting community structure and ecosystem processes

Dressed for Sex: Red as a Female Sexual Signal in Humans

Background: In many non-human primate species, a display of red by a female serves as a sexual signal to attract male conspecifics. Red is associated with sex and romance in humans, and women convey their sexual interest to men through a variety of verbal, postural, and behavioral means. In the present research, we investigate whether female red ornamentation in non-human primates has a human analog, whereby women use a behavioral display of red to signal their sexual interest to men. Methodology/Principal Findings: Three studies tested the hypothesis that women use red clothing to communicate sexual interest to men in profile pictures on dating websites. In Study 1, women who imagined being interested in casual sex were more likely to display red (but not other colors) on their anticipated web profile picture. In Study 2, women who indicated interest in casual sex were more likely to prominently display red (but not other colors) on their actual web profile picture. In Study 3, women on a website dedicated to facilitating casual sexual relationships were more likely to prominently exhibit red (but not other colors) than women on a website dedicated to facilitating marital relationships. Conclusions/Significance: These results establish a provocative parallel between women and non-human female primates in red signal coloration in the mating game. This research shows, for the first time, a functional use of color in women’s sexual self-presentation, and highlights the need to extend research on color beyond physics, physiology, and preference to psychological functioning