CSF sTREM2: Marking the tipping point between preclinical AD and dementia?

Biomarkers for Alzheimer's disease (AD) have improved our understanding of the temporal sequence of biological events that lead to AD dementia (Jack et al, 2013). AD is characterized neuropathologically by amyloid plaques comprised of the amyloid‐β peptide and neurofibrillary tangles comprised of tau. Brain amyloid deposition, as evidenced by a decline in amyloid‐β peptide 42 (Aβ42) in the cerebrospinal fluid (CSF) or by binding of amyloid PET ligands, is thought to be a key initiating event in AD and begins many years prior to the onset of dementia. A rise in CSF tau and phosphorylated tau in the setting of Aβ deposition appears to reflect neurodegeneration and also begins years prior to the onset of dementia but after Aβ deposition has begun to accumulate. Individuals with “preclinical AD,” that is, normal cognition but abnormal AD biomarkers, have a much higher risk for developing AD dementia but may remain cognitively normal for years (Vos et al, 2013). While deposition of amyloid and formation of tau tangles are necessary for AD to occur, it is likely that additional events involving inflammation or other processes contribute to crossing the tipping point from preclinical AD to AD dementia. Current efforts are aimed at defining the biomarker(s) that best predict the transition from cognitive normality to abnormality. A biomarker that is closely associated with the onset of cognitive decline could help us to understand the biological events that connect amyloid deposition and tangle formation to cognitive decline and could have significant practical value in AD diagnosis and clinical trial design

Losing Weight: A KECK Spectroscopic Survey of the Massive Cluster of Galaxies RX J1347-1145

We present a sample of 47 spectroscopically confirmed members of RX J1347-1145, the most luminous X-ray cluster of galaxies discovered to date. With two exceptions, all the galaxies in this sample have red B-R colors and red spectral indices, with spectra similar to old local ellipticals. Using all 47 cluster members, we derive a mean redshift of 0.4509\pm 0.003, and a velocity dispersion of 910\pm130 km/sec, which corresponds to a virial mass of 4.4 x 10^{14} h^{-1} Solar masses with an harmonic radius of 380 h^{-1} kpc. The derived total dynamical mass is marginally consistent with that deduced from the cluster's X-ray emission based on the analysis of ROSAT/ASCA images (Schindler et al. 1997), but not consistent with the more recent X-ray analyses of Allen (2000), Ettori, Allen & Fabian (2001) and Allen, Schmidt & Fabian (2002). Furthermore, the dynamical mass is significantly smaller than that derived from weak lensing (Fischer & Tyson 1997) and from strong lensing (Sahu et al. 1998). We propose that these various discrepant mass estimates may be understood if RX J1347-1145 is the product of two clusters caught in the act of merging in a direction perpendicular to the line of sight, although there is no evidence from the galaxy redshift distribution supporting this hypothesis. Even with this hypothesis, a significant part of the extremely high X-ray luminosity must still arise from non-virialized, presumably shocked, gas. Finally, we report the serendipitous discovery of a lensed background galaxy at z=4.083 which will put strong constraints on the lensing mass determination once its counter-image is securely identified.Comment: Minor changes to conform to version accepted by Ap

Wide-field weak lensing by RXJ1347-1145

We present an analysis of weak lensing observations for RXJ1347-1145 over a 43' X 43' field taken in B and R filters on the Blanco 4m telescope at CTIO. RXJ1347-1145 is a massive cluster at redshift z=0.45. Using a population of galaxies with 20<R<26, we detect a weak lensing signal at the p<0.0005 level, finding best-fit parameters of \sigma_v=1400^{+130}_{-140} km s^{-1} for a singular isothermal sphere model and r_{200} = 3.5^{+0.8}_{-0.2} Mpc with c = 15^{+64}_{-10} for a NFW model in an \Omega_m = 0.3, \Omega_\Lambda = 0.7 cosmology. In addition, a mass to light ratio M/L_R =90 \pm 20 M_\odot / L_{R\odot} was determined. These values are consistent with the previous weak lensing study of RXJ1347--1145 by Fischer and Tyson, 1997, giving strong evidence that systemic bias was not introduced by the relatively small field of view in that study. Our best-fit parameter values are also consistent with recent X-ray studies by Allen et al, 2002 and Ettori et al, 2001, but are not consistent with recent optical velocity dispersion measurements by Cohen and Kneib, 2002.Comment: accepted to ApJ, tentative publication 10 May 2005, v624

Deuteron electromagnetic form factors in a renormalizable formulation of chiral effective field theory

We calculate the deuteron electromagnetic form factors in a modified version of Weinberg's chiral effective field theory approach to the two-nucleon system. We derive renormalizable integral equations for the deuteron without partial wave decomposition. Deuteron form factors are extracted by applying the Lehmann-Symanzik-Zimmermann reduction formalism to the three-point correlation function of deuteron interpolating fields and the electromagnetic current operator. Numerical results of a leading-order calculation with removed cutoff regularization agree well with experimental data.Comment: 9 pages, 2 figure

Dienogest in long-term treatment of endometriosis

Endometriosis is a chronic disease primarily affecting women of childbearing age, in which endometriotic lesions form outside the uterus, typically leading to painful symptoms, fatigue, and infertility. The symptoms of endometriosis may cause significant impairment in quality of life and represent a substantial economic burden to patients, families, and society. There is no cure for endometriosis; management consists of alleviating pain and other symptoms, reducing endometriotic lesions, and improving quality of life. Recurrence after surgical intervention is common, while the clinical evidence to support the efficacy and safety of many medications currently used in endometriosis is limited. Dienogest is an oral progestin that has been investigated extensively in the treatment of endometriosis in two clinical programs performed in Europe and Japan, including dose-ranging, placebo-controlled, active comparator-controlled, and long-term (up to 65 weeks) studies. These studies demonstrated that dienogest 2 mg daily effectively alleviates the painful symptoms of endometriosis, reduces endometriotic lesions, and improves indices of quality of life. Dienogest showed a favorable safety and tolerability profile in these studies, with predictable adverse effects, high rates of patient compliance, and low withdrawal rates. This review article describes the clinical trial evidence that characterizes the efficacy and safety of dienogest in endometriosis, including two studies characterizing dienogest in long-term use. The relevance of these findings to the management of endometriosis in clinical practice is discussed

Amend the Lanham Act: Trademark Infringement Needs A Statute of Limitations

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