A randomized crossover trial assessing patient preference for two different types of portable infusion-pump devices

Background: A variety of anticancer agents are better tolerated and more effective if given as continuous compared to bolus administration. Portable pump devices are needed to allow outpatient continuous infusion. Different types of portable pumps are available and we tested patient preference in a randomized crossover design. Patients and methods: Patients on continuous infusion fluorouracil were randomly assigned to start treatment with an elastomeric infusor (Baxter) or a mechanical, electronically controlled pump (CADD-1™, Pharmacia) and crossed over to the alternative model after three weeks. After exposure to both pump types patients were asked to indicate their preferred device. Results: After 10 patients the study was closed because all study participants preferred the elastomeric pump (P < 0.01). Reasons were pump weight (100%), smaller pump size (89%), interference with daily activities (89%), user friendliness (56%), impact on sleep (44%), and lack of technical problems (22%). Although the mechanical pump required more handling time for the first two refillings, the learning curve suggested about equal time requirement thereafter. Conclusion: In the interest of patient comfort, the disposable elastomeric infusor is an acceptable alternative to the more accurate electronically controlled pumps especially for drugs with a short half-life and a favorable toxicity profil

Early alterations in the MCH system link aberrant neuronal activity and sleep disturbances in a mouse model of Alzheimer’s disease

Early Alzheimer’s disease (AD) is associated with hippocampal hyperactivity and decreased sleep quality. Here we show that homeostatic mechanisms transiently counteract the increased excitatory drive to CA1 neurons in App NL-G-F mice, but that this mechanism fails in older mice. Spatial transcriptomics analysis identifies Pmch as part of the adaptive response in App NL-G-F mice. Pmch encodes melanin-concentrating hormone (MCH), which is produced in sleep–active lateral hypothalamic neurons that project to CA1 and modulate memory. We show that MCH downregulates synaptic transmission, modulates firing rate homeostasis in hippocampal neurons and reverses the increased excitatory drive to CA1 neurons in App NL-G-F mice. App NL-G-F mice spend less time in rapid eye movement (REM) sleep. App NL-G-F mice and individuals with AD show progressive changes in morphology of CA1-projecting MCH axons. Our findings identify the MCH system as vulnerable in early AD and suggest that impaired MCH-system function contributes to aberrant excitatory drive and sleep defects, which can compromise hippocampus-dependent functions

ARMC9 and TOGARAM1 define a Joubert syndrome-associated protein module that regulates axonemal post-translational modifications and cilium stability

Joubert syndrome (JBTS) is a recessive neurodevelopmental ciliopathy, characterized by a pathognomonic hindbrain malformation. All known JBTS-genes encode proteins involved in the structure or function of primary cilia, ubiquitous antenna-like organelles essential for cellular signal transduction. Here, we use the recently identified JBTS-associated protein ARMC9 in tandem-affinity purification and yeast two-hybrid screens to identify a novel ciliary module composed of ARMC9-TOGARAM1-CCDC66-CEP104- CSPP1. TOGARAM1-variants cause JBTS and disrupt its interaction with ARMC9. Using a combination of protein interaction analyses and characterization of patient-derived fibroblasts, CRISPR/Cas9-engineered zebrafish and hTERT-RPE1 cells, we demonstrate that dysfunction of ARMC9 or TOGARAM1 results in short cilia with decreased axonemal acetylation and glutamylation, but relatively intact transition zone function. Aberrant serum-induced ciliary resorption and cold-induced depolymerization in both ARMC9 and TOGARAM1 patient cells lines suggest a role for this new JBTS-associated protein complex in ciliary stability

Effective Long-Distance Pollen Dispersal in Centaurea jacea

BACKGROUND: Agri-environment schemes play an increasingly important role for the conservation of rare plants in intensively managed agricultural landscapes. However, little is known about their effects on gene flow via pollen dispersal between populations of these species. METHODOLOGY/PRINCIPAL FINDINGS: In a 2-year experiment, we observed effective pollen dispersal from source populations of Centaurea jacea in restored meadows, the most widespread Swiss agri-environment scheme, to potted plants in adjacent intensively managed meadows without other individuals of this species. Potted plants were put in replicated source populations at 25, 50, 100 m and where possible 200 m distance from these source populations. Pollen transfer among isolated plants was prevented by temporary bagging, such that only one isolated plant was accessible for flower visitors at any one time. Because C. jacea is self-incompatible, seed set in single-plant isolates indicated insect mediated effective pollen dispersal from the source population. Seed set was higher in source populations (35.7+/-4.4) than in isolates (4.8+/-1.0). Seed set declined from 18.9% of that in source populations at a distance of 25 m to 7.4% at 200 m. At a distance of 200 m seed set was still significantly higher in selfed plants, indicating long-distance effective pollen dispersal up to 200 m. Analyses of covariance suggested that bees contributed more than flies to this long-distance pollen dispersal. We found evidence that pollen dispersal to single-plant isolates was positively affected by the diversity and flower abundance of neighboring plant species in the intensively managed meadow. Furthermore, the decline of the dispersal was less steep when the source population of C. jacea was large. CONCLUSIONS: We conclude that insect pollinators can effectively transfer pollen from source populations of C. jacea over at least 200 m, even when "recipient populations" consisted of single-plant isolates, suggesting that gene flow by pollen over this distance is very likely. Source population size and flowering environment surrounding recipient plants appear to be important factors affecting pollen dispersal in C. jacea. It is conceivable that most insect-pollinated plants in a network of restored sites within intensively managed grassland can form metapopulations, if distances between sites are of similar magnitude as tested here

Reconstructed Dynamics of Rapid Extinctions of Chaparral-Requiring Birds in Urban Habitat Islands

The distribution of native, chaparral-requiring bird species was determined for 37 isolated fragments of canyon habitat ranging in size from 0.4 to 104 hectares in coastal, urban San Diego County, California The area of chaparral habitat and canyon age (time since isolation of the habitat fragment) explains most of the variation in the number of chaparral-requiring bird species. In addition, the distribution of native predators may influence species number. There is statistical evidence that coyotes control the populations of smaller predators such as foxes and domestic cats. The absence of coyotes may lead to higher levels of predation by a process of mesopredator release. The distance of canyons from other patches of chaparral habitat does not add significantly to the explained variance in chaparral-requiring species number–probably because of the virtual inability of most chaparral-requiring species to disperse through developed areas and nonscrub habitats. These results and other lines of evidence suggest that chaparral-requiring birds in isolated canyons have very high rates of extinction, in part because of their low vagility. The best predictors of vulnerability of the individual species are their abundances (densities) in undisturbed habitat and their body sizes; together these two variables account for 95 percent of the variation in canyon occupancy. A hypothesis is proposed to account for the similarity between the steep slopes of species-area curves for chaparral-requiring birds and the slopes for some forest birds on small islands or in habitat fragments. The provision of corridors appears to be the most effective design and planning feature for preventing the elimination of chaparral-requiring species in a fragmented landscape.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74761/1/j.1523-1739.1988.tb00337.x.pd

Food for pollinators: quantifying the nectar and pollen resources of urban flower meadows

Planted meadows are increasingly used to improve the biodiversity and aesthetic amenity value of urban areas. Although many ‘pollinator-friendly’ seed mixes are available, the floral resources these provide to flower-visiting insects, and how these change through time, are largely unknown. Such data are necessary to compare the resources provided by alternative meadow seed mixes to each other and to other flowering habitats. We used quantitative surveys of over 2 million flowers to estimate the nectar and pollen resources offered by two exemplar commercial seed mixes (one annual, one perennial) and associated weeds grown as 300m2 meadows across four UK cities, sampled at six time points between May and September 2013. Nectar sugar and pollen rewards per flower varied widely across 65 species surveyed, with native British weed species (including dandelion, Taraxacum agg.) contributing the top five nectar producers and two of the top ten pollen producers. Seed mix species yielding the highest rewards per flower included Leontodon hispidus, Centaurea cyanus and C. nigra for nectar, and Papaver rhoeas, Eschscholzia californica and Malva moschata for pollen. Perennial meadows produced up to 20x more nectar and up to 6x more pollen than annual meadows, which in turn produced far more than amenity grassland controls. Perennial meadows produced resources earlier in the year than annual meadows, but both seed mixes delivered very low resource levels early in the year and these were provided almost entirely by native weeds. Pollen volume per flower is well predicted statistically by floral morphology, and nectar sugar mass and pollen volume per unit area are correlated with flower counts, raising the possibility that resource levels can be estimated for species or habitats where they cannot be measured directly. Our approach does not incorporate resource quality information (for example, pollen protein or essential amino acid content), but can easily do so when suitable data exist. Our approach should inform the design of new seed mixes to ensure continuity in floral resource availability throughout the year, and to identify suitable species to fill resource gaps in established mixes