Tuning the relaxation rates of dual-mode T?/T? nanoparticle contrast agents: a study into the ideal system

Magnetic resonance imaging (MRI) is an excellent imaging modality. However the low sensitivity of the technique poses a challenge to achieving an accurate image of function at the molecular level. To overcome this, contrast agents are used; typically gadolinium based agents for T? weighted imaging, or iron oxide based agents for T? imaging. Traditionally, only one imaging mode is used per diagnosis although several physiological situations are known to interfere with the signal induced by the contrast agents in each individual imaging mode acquisition. Recently, the combination of both T? and T? imaging capabilities into a single platform has emerged as a tool to reduce uncertainties in MR image analysis. To date, contradicting reports on the effect on the contrast of the coupling of a T? and T? agent have hampered the application of these specialised probes. Herein, we present a systematic experimental study on a range of gadolinium-labelled magnetite nanoparticles envisioned to bring some light into the mechanism of interaction between T? and T? components, and advance towards the design of efficient (dual) T? and T? MRI probes. Unexpected behaviours observed in some of the constructs will be discussed. In this study, we demonstrate that the relaxivity of such multimodal probes can be rationally tuned to obtain unmatched potentials in MR imaging, exemplified by preparation of the magnetite-based nanoparticle with the highest T? relaxivity described to date

Functional significance of M-type potassium channels in nociceptive cutaneous sensory endings

M-channels carry slowly activating potassium currents that regulate excitability in a variety of central and peripheral neurons. Functional M-channels and their Kv7 channel correlates are expressed throughout the somatosensory nervous system where they may play an important role in controlling sensory nerve activity. Here we show that Kv7.2 immunoreactivity is expressed in the peripheral terminals of nociceptive primary afferents. Electrophysiological recordings from single afferents in vitro showed that block of M-channels by 3 μM XE991 sensitized Aδ- but not C-fibers to noxious heat stimulation and induced spontaneous, ongoing activity at 32°C in many Aδ-fibers. These observations were extended in vivo: intraplantar injection of XE991 selectively enhanced the response of deep dorsal horn (DH) neurons to peripheral mid-range mechanical and higher range thermal stimuli, consistent with a selective effect on Aδ-fiber peripheral terminals. These results demonstrate an important physiological role of M-channels in controlling nociceptive Aδ-fiber responses and provide a rationale for the nocifensive behaviors that arise following intraplantar injection of the M-channel blocker XE991

Patterns of competition and insolation along a canopy disturbance severity gradient: implications for the Quercus bottleneck

Regeneration failure of Quercus has been widely reported throughout the Central Hardwood Forest of the eastern United States across all but the most xeric site types. Quercus seedlings are often abundant in upland hardwood stands, but typically fail to recruit to larger size classes (i.e. the Quercus bottleneck). The goal of my study was to investigate the competition with small-sized Quercus stems to elucidate what variables may cause resistance or facilitation of Quercus recruitment. I established a 2 ha plot in the Sipsey Wilderness, AL that was subdivided into 5 x 5 m quadrats to encompass the entire extent of damage caused by an EF1 tornado in 2011. The study area encompassed a range of damage (light, moderate, severe), starting from the center of the tornado tract and ending in an undamaged area (control). The canopy disturbance provided a range of light conditions in the understory (0.5–91.0% full sunlight). In each quadrat, the height of all small-sized Quercus stems (≥ 0.5 m in height to >5 cm DBH) were measured and recorded. The nearest neighbor was identified by species and measured for height and distance from the focal Quercus stem. Photosynthetically active radiation was quantified at 1.4 m above the forest floor. Quercus’ competition was largely interspecific and the majority of competitors were shade-tolerant species such as Acer saccharum and Ostrya virginiana. Competitive indices of Quercus’ primary competitors were significantly different (p 0.01) effect on the competitive ability of species. Spatial patterns of Quercus stems, their nearest neighbor, and percent full sunlight were analyzed at 5 x 5 m, 10 x 10 m, and 20 x 20 m. Analysis at a fine-scale resolution revealed spatial patterns which would otherwise not be apparent at coarser scales. Creative and flexible silvicultural techniques may need to be implemented at finer scales to optimize the recruitment of Quercus spp. (Published By University of Alabama Libraries

Defining the medical sphere

Part of the debate on cost containment in health care systems can be characterized as applied political philosophy. Three philosophical directions can be traced. (1) Norman Daniels and Ronald Dworkin advocate a health care distributional system based on a Rawls' A Theory of Justice. (2) Tristram Engelhardt defends a market based approach, reminiscent of Nozick's Anarchy, State, and Utopia. (3) Daniel Callahan advocates a communitarian strategy which resembles the work of Christopher Lasch and Robert Bellah. In the first part of this article these three strategies will be discussed. Occasionally health care philosophers also refer to Michael Walzer's Spheres of Justice. However, no one has undertaken the task to design a health care distributional system style Michael Walzer. According to the author this is to be regretted. Walzer argues that Americans ought to establish a health care system resembling the British National Health Service, because the concepts and categories in which they discuss the distribution of medical goods, as well as established institutions such as Medicare and Medicaid, reveal that they have been committed to something akin to the NHS all along. Walzer's critics point out that a large part of medical goods in the United States is bought and sold on the market. Why should the institution of private health care insurance not be taken as evidence that a straightforward market system is what Americans have wanted in their heart of hearts? In the second part of this article it will be argued that the controversy between Walzer and his critics is based on a serious mistake in Spheres of Justice. Once this mistake has been rectified Walzer's theory of justice might be a fruitful approach to the discussion of cost containment in health care services