In situ analysis of neuronal dynamics and positional cues in the patterning of nerve connections

Recently developed imaging techniques permit individual cells to be uniquely labeled and followed over time as development proceeds in intact vertebrate embryos. Small groups of cells in the developing eye rudiment of the frog Xenopus have been labeled with the vital dyes DiI, lysinated fluorescein dextran (LFD) or lysinated rhodamine dextran (LRD). Individual optic axons and their growth cones were clearly visible in the intact living animal using confocal microscopy or epifluorescence microscopy with a low light level video camera and computer-based video image enhancement. To follow the dynamics of single optic nerve fiber terminal arborizations, small groups of cells, or even single retinal ganglion cells, were labeled with DiI, and the resulting labeled optic nerve fibers were imaged using a confocal microscope. The images show a profound alteration in morphology from day to day, demonstrating that optic nerve terminal arborizations are dynamic structures constantly extending and retracting branches. To follow the topography of the developing projection and analyze the cues that guide its formation, small groups of eyebud cells from LFD- and LRD-labeled donor embryos were grafted to an unlabeled host in either a location equivalent to that from which they had been removed (homotopic grafts) or a non-equivalent location (heterotopic grafts). Axons from homotopic grafts projected to the tectum as expected from the adult topography of the retinotectal projection. Dorsoventral topography was present from the time that the optic nerve fibers were observable in the tectum, in agreement with previous work. Nasotemporal topography was subtle or absent for the first few days, and then slowly refined. The importance of positional cues was tested by performing heterotopic eyebud grafts, in which the labeled eyebud cells are grafted to inappropriate places in the host eyebud. The heterotopic grafts appeared to integrate with the ectopic site in the eyebud in a functional manner. They should, therefore, project to the tectum together with their new neighbors if neighbor interactions or activity-based cues were of primary importance in the initial patterning of the map. However, the experiments showed that the axons from heterotopic grafts always behaved in a fashion appropriate to their position of origin in the donor, regardless of their final position in the host. These observations indicate that small groups of eyebud cells (as small as a single cell) possess positional information that plays a dominant role in guiding the optic nerve fibers to their target sites in the tectum

The pharmacokinetics of nebulized nanocrystal budesonide suspension in healthy volunteers.

Nanocrystal budesonide (nanobudesonide) is a suspension for nebulization in patients with steroid-responsive pulmonary diseases such as asthma. The pharmacokinetics and safety of the product were compared to those of Pulmicort Respules. Sixteen healthy volunteers were administered nanobudesonide 0.5 and 1.0 mg, Pulmicort Respules 0.5 mg, and placebo in a four-way, randomized crossover design. All nebulized formulations were well tolerated, with no evidence of bronchospasm. Nebulization times were significantly shorter for nanobudesonide compared to Pulmicort Respules. Because of a low oral bioavailability, plasma concentration of budesonide is a good marker of lung-delivered dose. The pharmacokinetics of nanobudesonide 0.5 and 1.0 mg were approximately dose proportional with respect to Cmax, AUC(0-t), and AUC(0-infinity). Nanobudesonide 0.5 mg and Pulmicort Respules 0.5 mg exhibited similar AUCs, suggesting a similar extent of pulmonary absorption. A higher Cmax was noted with nanobudesonide 0.5 mg, and the tmax was significantly different, suggesting a more rapid rate of drug delivery of nanobudesonide 0.5 mg than Pulmicort Respules. In conclusion, nebulized nanobudesonide 0.5 mg was safe in healthy volunteers, with a similar extent of absorption as Pulmicort Respules

Spatial Predictive Modeling and Remote Sensing of Land Use Change in the Chesapeake Bay Watershed

This project was focused on modeling the processes by which increasing demand for developed land uses, brought about by changes in the regional economy and the socio-demographics of the region, are translated into a changing spatial pattern of land use. Our study focused on a portion of the Chesapeake Bay Watershed where the spatial patterns of sprawl represent a set of conditions generally prevalent in much of the U.S. Working in the region permitted us access to (i) a time-series of multi-scale and multi-temporal (including historical) satellite imagery and (ii) an established network of collaborating partners and agencies willing to share resources and to utilize developed techniques and model results. In addition, a unique parcel-level tax assessment database and linked parcel boundary maps exists for two counties in the Maryland portion of this region that made it possible to establish a historical cross-section time-series database of parcel level development decisions. Scenario analyses of future land use dynamics provided critical quantitative insight into the impact of alternative land management and policy decisions. These also have been specifically aimed at addressing growth control policies aimed at curbing exurban (sprawl) development. Our initial technical approach included three components: (i) spatial econometric modeling of the development decision, (ii) remote sensing of suburban change and residential land use density, including comparisons of past change from Landsat analyses and more traditional sources, and (iii) linkages between the two through variable initialization and supplementation of parcel level data. To these we added a fourth component, (iv) cellular automata modeling of urbanization, which proved to be a valuable addition to the project. This project has generated both remote sensing and spatially explicit socio-economic data to estimate and calibrate the parameters for two different types of land use change models and has undertaken analyses of these models. One (the CA model) is driven largely by observations on past patterns of land use change, while the other (the EC model) is driven by mechanisms of the land use change decision at the parcel level. Our project may be the first serious attempt at developing both types of models for the same area, using as much common data as possible. We have identified the strengths and weaknesses of the two approaches and plan to continue to revise each model in the light of new data and new lessons learned through continued collaboration. Questions, approaches, findings, publication and presentation lists concerning the research are also presented

Fossil Pollen and Insect Evidence for Postglacial Environmental Conditions, Nushagak and Holitna Lowland Regions, Southwest Alaska

This paper discusses the results of pollen and insect analyses of postglacial samples from the Nushagak and Holitna lowlands, southwest Alaska. Although radiocarbon dating control is poor, the samples can be arranged in a relative-age sequence based on stratigraphic occurrence. The fossil pollen data record the regional transition from a late-glacial dry graminoid tundra through the postglacial Birch, Alder, and Spruce zones. The lack of xeric insect species in the early postglacial suggests that the lowlands of southwest Alaska experienced maritime climatic conditions, in contrast to the interior. Rapid climatic warming is subsequently indicated by the fossil insect data, although the arrival of alder in the region postdates 8500 yr BP. There is no evidence for coniferous forest in the Nushagak lowland at any time in the postglacial, although spruce arrived in the Holitna lowland in the mid-postglacial.Key words: pollen analysis, fossil insects, paleoenvironments, postglacial, southwest AlaskaRÉSUMÉ. Cet article traite des résultats d’analyses polliniques et d’insectes d’échantillons postglaciaires venant des basses-terres de Nushagak et d’Holitna, dans le sud-ouest de l’Alaska. Bien que le contrôle de la datation par le radiocarbone soit médiocre, les échantillons peuvent être classés en ordre d’âger elatif, d’après leur occurrence stratigraphique. Les données de pollens fossiles traduisent le passage de la région d’une toundra sèche de graminées datant de la fin de l’époque glaciaire, à des zones postglaciaires de bouleaux, d’aulnes et d’épicéas. L’absence d’espèces d’insectes xérophiles au début du postglaciaire donne à penser que les basses-terres du sud-ouest de l’Alaska ont connu des conditions climatiques maritimes, contrairement à l’intérieur. Les données sur les insectes fossiles permettent donc d’établir qu’il y a eu un réchauffement climatique rapide, bien que l’arrivée de l’aulne dans la région soit postérieure à 8500 ans avant le présent. On n’a pas de preuve de l’existence d’une forêt de coniferes dans la basse-terre de Nushagak à un moment quelconque du postglaciaire, bien que l’épicéa fasse son arrivée dans la basse-terre d’Holitna au milieu du postglaciaire.Mots clés: analyse pollinique, insectes fossiles, paléoenvironnements, postglaciaire, sud-ouest de l’Alask

Shaping attitudes: the association between prior contact with residential aged care and resistance to enter residential aged care

Background: The ageing population is increasing, and negative attitudes towards older people are all too common and largely overlooked. However, little research has examined how ageist, prejudice, and discrimination, that often occur in healthcare settings, impact the community's perceptions of entering Residential Aged Care (RAC) in the future. In particular, studies have not investigated how contact with RAC influences individuals’ attitudes towards RAC facilities, residents and staff. This study is the first to examine individuals’ resistance towards living in RAC using the contact hypothesis, a theory of prejudice reduction. Aims: To explore how positive or negative contact with RAC residents and staff impacts individuals’ behavioural intentions towards entering RAC in the future. To examine whether perceptions of trust, independence and RAC staff mediate the relationship between contact and behavioural intentions towards entering RAC in the future. Design: A cross-sectional survey design. Method: Data were collected via online surveys using contact (positive or negative), trust, independence, perceptions of RAC staff and resistance levels (mild refusal or extreme refusal) measures. Participants (n\ua0=\ua0373) from Australia and USA were recruited using social media, word of mouth and Amazons Mechanical Turk. Findings: Individuals who experienced negative contact with RAC residents and staff were more likely to report intense resistance to RAC, “I would rather die than enter RAC”. Whereas, positive contact with RAC residents and staff was associated with reductions in the adverse appraisal of RAC staff; a diminished perception that individuals lost their independence, and an increased trust in RAC residents, facilities and staff. Participants from USA reported greater levels of resistance towards RAC in comparison with participants from Australia. This study demonstrates how interactions with RAC residents, facilities and staff are critical in shaping attitudes towards RAC. Implications for practice: It is recommended that the public are exposed to opportunities where they can experience positive contact with RAC. RAC facilities can promote interaction between the public and RAC residents through encouraging participation in community partnership programs/intergenerational programs

PEPFAR Public Health Evaluation - Care and Support - Phase 2 Kenya

Phase 2 consisted of a longitudinal cohort study to measure patient-reported outcomes of care and support, a costing survey, and qualitative interviews to understand patient and carer experiences

Late Quaternary Marine and Terrestrial Environments, Northwestern Baffin Island, Northwest Territories

Paleoenvironmental data were analyzed from terrestrial, lake, and marine sediments collected near Arctic Bay, Baffin Island, N.W.T. Eighteen new radiocarbon dates provide chronological control, superseding earlier results. Spuriously old dates were obtained from both sandy peats and low-organic lake sediments. The most reliable dates were from marine shells and foraminifera. They indicate that déglaciation was underway by 9000 BP rather than 16,000 BP. Over the period of the record, the local environment was characterized by a high arctic pollen assemblage dominated by grass, sedge, and willow; a middle Holocene warm period is indicated by increased willow, herb, and moss values. Sea-ice conditions were severe enough to inhibit the growth of diatoms until ca. 6300 BP and ice proximal and deglacial conditions prevailed in the fiords until ca. 6000 BP. Diatom productivity increased between 3000 BP and 2500 BP, suggesting warmer surface waters and less sea ice. After 2000 BP diatom accumulation decreased sharply, due to a cooling of climate. The foraminifera indicate a major change in bottom water conditions ca. 4000 BP as the benthic species shift from a calcareous to an arenaceous assemblage.On a procédé à l'analyse des données paléoenvironnementales tirées de sédiments terrestres, marins et lacustres, près de Arctic Bay. Dix-huit nouvelles dates au radiocarbone ont permis d'établir une nouvelle chronologie. Les dates les plus anciennes, et les moins fiables, ont été obtenus dans des tourbes sableuses et des sédiments lacustres à basse teneur organique. Les dates les plus sûres proviennent de coquillages marins et des foraminifères. Elles indiquent que la déglaciation était en cours dès 9000 BP plutôt qu'à 16 000 BP. Pendant la période relevée, l'environnement dans le haut Arctique était caractérisé au niveau local par un assemblage pollinique dominé par l'herbe, le carex et le saule; à l'Holocène moyen, les valeurs croissantes du saule, de l'herbe et de la mousse reflètent une période chaude. La densité de la glace marine était assez forte pour empêcher la croissance des diatomées jusqu'à 6300 BP; la déglaciation s'est poursuivie jusque vers 6000 BP dans les fjords. La reproduction des diatomées a augmenté entre 3000 et 2500 BP en raison de températures de surface plus chaudes et une diminution des glaces marines. Après 2000 BP, l'accumulation des diatomées a décru abruptement en raison d'un refroidissement climatique. Les foraminifères démontrent un changement important survenu dans l'état des eaux profondes vers 4000 BP puisqu'il y a eu remplacement des espèces benthoniques à test calcaire par des espèces à test agglutiné.Man hat Palâoumweltdaten von Erd-, See- und Meeres-Sedimenten analysiert, die man in der Nâhe der Arctic Bay, lnsel Baffin, Nordwest-Territorien gesammelt hat. Achtzehn neue Radiocarbondaten liefern eine chronologische Kontrolle und ersetzen so fruhere Resultate. Faische alte Daten hat man sowohi aus sandigem Ton1 wie auch aus Seesedimenten mit niedrigem organischem Gehalt gewonnen. Die zuver-làssigsten Daten stammen von Meeres-muscheln und Foraminiferen. Sie zeigen, dass die Enteisung urn 9000 v.u.Z. und nicht um 16,000 v.u.Z. im Gange war. Liber den Zeitraum des Belegs charakterisierte sich die lokale Umwelt durch eine Pollen-Zusammensetzung der hohen Arktis, die von Gras, Schilfgras und Weide beherrscht war; auf eine warme Période wâhrend des mittleren Holozàns weisen zunehmende Weiden-, Gras- und Mooswerte. Die Meereseisbedingungen waren streng genug, um das Wachstum von Diatomeen bis etwa 6300 v.u.Z. zu verhindern und Proximaleis und Enteisungsbedingungen herrschten in den Fjords bis etwa 6000 v.u.Z. vor. Die Reproduktion von Diatomeen nahm zwischen 3000 v.u.Z. und 2500 v.u.Z. zu, was auf wàrmeres Oberflàchenwasser und weniger Meereseis schliessen làsst. Nach 2000 v.u.Z. nahm die Diatomeen-Akkumulation wegen einer Klimaabkuhlung plôtzlich ab. Die Foraminiferen zeigen einen betràchtlichen Wechsel der Bedingungen im tiefen Wasser um etwa 4000 v.u.Z., wenn die benthonischen Spezies von einer kalkartigen zu einer sandigen Zusammensetzung ubergehen

Modulus variation of composite graphite electrodes in lithium-ion batteries during electrochemical cycling

Graphite is currently the most common anode material used in commercial lithium-ion batteries. During battery charging and discharging processes, lithium ions intercalate into and deintercalate from graphite, forming several distinct stages of graphite-lithium intercalation compounds (G-LICs). Each stage of G-LIC has a unique spacing between graphene layers, with the spacing increasing for increasing lithium content. In graphite-based composite electrodes (graphite particles in a porous polymer matrix), the changing layer spacing leads to stress and strain evolution on the composite length scale. In two separate experiments, we use substrate-curvature measurements to monitor stress changes in a thin electrode constrained on an inert, rigid substrate, and we use digital image correlation to track strain changes in a free-standing, unconstrained electrode. Combining the in-situ stress and strain analyses enables us to extract the change in the apparent modulus of the composite graphite electrode as a function of electrode potential and lithium content. As expected, we found that constrained electrodes develop compressive stress during lithiation (~10 MPa) and that unconstrained electrodes undergo free expansion (~1.5% linear strain). Interestingly, the apparent modulus of the electrode increases the most significantly during the formation of the dilute stage I compound, increases slightly with the formation of the stage IV, dilute stage II, and stage II compounds, and then decreases with the formation of the stage I compound (LiC 6). During delithiation, unconstrained electrodes contract, recovering nearly their original size. In constrained electrodes during delithation, however, the compressive stress is first relaxed, and then a tensile stress develops and is subsequently relaxed. The tensile stress leads to an apparent softening of the composite electrode over a broad range of electrode potential and capacity. At the end of one complete lithiation/delithiation cycle, the apparent modulus returns to approximately its original value. The evolution of stress, strain, and modulus data provides quantitative information on the coupled electro-chemo-mechanical response of battery electrodes and insight on material strategies to increase battery reliability