In vivo multiphoton imaging reveals gradual growth of newborn amyloid plaques over weeks

The kinetics of amyloid plaque formation and growth as one of the characteristic hallmarks of Alzheimer’s disease (AD) are fundamental issues in AD research. Especially the question how fast amyloid plaques grow to their final size after they are born remains controversial. By long-term two-photon in vivo imaging we monitored individual methoxy-X04-stained amyloid plaques over 6 weeks in 12 and 18 months old Tg2576 mice. We found that in 12 months old mice, newly appearing amyloid plaques were initially small in volume and subsequently grew over time. The growth rate of plaques was inversely proportional to their volume; thus amyloid plaques that were already present at the first imaging time point grew over time but slower compared to new plaques. Additionally, we analyzed 18 months old Tg2576 mice in which we neither found newly appearing plaques nor a significant growth of pre-existing plaques over 6 weeks of imaging. In conclusion, newly appearing amyloid plaques are initially small in size but grow over time until plaque growth can not be detected anymore in aged mice. These results suggest that drugs that target plaque formation should be most effective early in the disease, when plaques are growing

The potential for AMS analysis of Be-10 using BeF-

The potential for the measurement of Be-10/Be-9 ratios near 10(-12), using (BeF-)-Be-10-F-19 ions and small accelerator mass spectrometry (AMS) systems, is described. In comparison with the use of (10)Be16O(-) ions the interference from the B-10 isobar is reduced by about five orders of magnitude. This is because molecular ions of mass 29 containing B-10 are much rarer than ions of mass 26 such as BO-. In addition, the ion HBeF- has not been observed, thereby reducing a possible interference from BeH2+, which allows Be-10(2+) to be counted with small AMS systems. Three molecular ions, BF-, BBeB- and H2BO-, are found to be mainly responsible for producing the B-10(2+) ions entering the final detector. The observation of weak beams of BF- is consistent with, but does not prove, the theoretical prediction that the ion will exist only as an excited metastable state. In that case a lifetime longer than similar to1 mus would be needed to explain the observed flux of BF-. The overall efficiency when using BeF- is expected to be roughly comparable to using BeO- on similar AMS systems, because of the simplifications introduced, but possibly with greater potential for further development. (C) 2004 Elsevier B.V. All rights reserved

Iodine 129/CFC 11 transit times for Denmark Strait Overflow Water in the Labrador and Irminger Seas

Iodine 129 discharged from nuclear fuel reprocessing plants in France and the United Kingdom is transported into the Nordic Seas on timescales of 3 - 5 years. Tracer I-129 is subsequently injected into intermediate waters that overflow the sills between Greenland, Iceland, and Scotland and ventilate the North Atlantic Deep Waters ( NADW). During the early 1990s, discharges of I-129 increased by 600%, resulting in a large, well- resolved tracer " front'' whose passage through the Nordic Seas is presently being observed by a time series of I-129 measurements on the WOCE ( AR7W) section in the Labrador Sea. The highest I-129 levels were measured below depths of 3000 m in Denmark Strait Overflow Water ( DSOW). These levels increased by about 300% between 1997 and 2001 to values > 40 x 10(7) atoms/ L, indicating that the leading edge of the tracer " front'' from the early 1990s was being observed entering the NADW. Using a simple mixing/ advection model, I-129 and CFC 11 results were used to calculate transit times of 0.4 - 2.6 years for the flow of DSOW from formation regions in the Nordic Seas to the Labrador Sea. Measurements on samples collected in the Irminger Sea in 2001 gave transit times of 0.3 years for core DSOW immediately south of Denmark Strait and about 2 years for locations off the southern tip of Greenland. An increase in DSOW transit times observed in the Labrador Sea between 1999 and 2001 probably reflects a more general weakening in the subpolar gyre of the North Atlantic during the 1990s

Superior efficacy of St John's wort extract WS^®5570 compared to placebo in patients with major depression: a randomized, double-blind, placebo-controlled, multi-center trial [ISRCTN77277298]

<p>Abstract</p> <p>Background</p> <p>The aim of the current study was to assess the antidepressant efficacy and safety of <it>Hypericum perforatum </it>(St. John's wort) extract WS^®5570 at doses of 600 mg/day in a single dose and 1200 mg/day in two doses.</p> <p>Methods</p> <p>The participants in this double-blind, randomized, placebo-controlled, multi-center clinical trial were male and female adult out-patients with an episode of mild or moderate major depressive episode (single or recurrent episode, DSM-IV criteria). As specified by the relevant guideline, the study was preceded by a medication-free run-in phase. For the 6-week treatment, 332 patients were randomized: 123 to WS^®5570 600 mg/day, 127 to WS^®5570 1200 mg/day, and 82 to placebo. The primary outcome measure was the change in total score on the Hamilton Rating Scale for Depression (HAM-D, 17-item version) between baseline and endpoint. Additional measures included the number of responders, the number of patients in remission, and several other standard rating scales. Efficacy and safety were assessed after 2 and 6 weeks. The design included an interim analysis performed after randomization with the option of early termination.</p> <p>Results</p> <p>After 6 weeks of treatment, mean ± standard deviation decreases in HAM-D total scores of 11.6 ± 6.4, 10.8 ± 7.3, and 6.0 ± 8.1 points were observed for the WS^®5570 600 mg/day, 1200 mg/day and placebo groups, respectively (endpoint analysis). Secondary measures of treatment efficacy also showed that both WS^®5570 groups were statistically superior to placebo. Significantly more patients in the WS^®5570 treatment groups than in the placebo group showed treatment response and remission. WS^®5570 was consistently more effective than placebo in patients with either less severe or more severe baseline impairment. The number of patients who experienced remission was higher in the WS^®5570 1200 mg/day group than the WS^®5570 600 mg/day group. The incidence of adverse events was low in all groups. The adverse event profile was consistent with the known profile for <it>Hypericum </it>extract preparations.</p> <p>Conclusion</p> <p><it>Hypericum perforatum </it>extract WS^®5570 at doses of 600 mg/day (once daily) and 1200 mg/day (600 mg twice daily) were found to be safe and more effective than placebo, with comparable efficacy of the WS^®5570 groups for the treatment of mild to moderate major depression.</p

Professional Associations

A professional association is a body of a knowledge-based group, whose main concern is the promotion of technical standards (Torstendahl 1990). Anglo-American sociology of professions usually refers to professional associations as a sign of the maturity of a professional project (Carr-Saunders and Wilson 1933; Wilensky 1964; Larson 1979). Classic references from the sociology of professions identify the existence of stages of professionalization. Professional associations may thus be conceived as a stage of professionalization among others, like the creation of specific training or the existence of a licence law and of an ethical code (Wilensky 1964). Professional associations can also be understood as a strategy of an occupational group to strengthen its status, reducing conflicts among professionals and mobilizing resources (Selander 1990). This strategy usually tends to closure (Torstendahl 1990). In this sense, professional associations test the ability of members...info:eu-repo/semantics/publishedVersio