Evaluation of alpha-synuclein immunohistochemical methods for the detection of Lewy-type synucleinopathy in gastrointestinal biopsies

The observation showing that Lewy type synucleinopathy (LTS), the pathological hallmark of Parkinson’s disease (PD), is found in the gut of almost all PD subjects led to a substantial amount of research to develop a diagnostic procedure in living patients based on endoscopically obtained gastrointestinal biopsies. However, the existing studies have provided conflicting results regarding the sensitivity and specificity of gastrointestinal biopsies for the detection of LTS. We therefore undertook a multi-center staining and blinded judging of a common set of slides from colonic biopsies to determine the optimal protocol for the detection of LTS. Four different immunohistochemical methods, developed in four separate expert laboratories, were evaluated for their sensitivity and specificity to detect enteric LTS. Test sets of formalin-fixed, paraffin-embedded sections from biopsies of 9 PD subjects and 3 controls were stained with the 4 methods and graded by 4 different observers. Four types of staining morphology (granular staining in the lamina propria, perivascular/vascular wall staining in the submucosa, lacy-granular pattern in the submucosa and epithelial cell nuclear staining) were variably observed in the slides stained by the 4 methods. Positive alpha-synuclein staining was observed by all 5 judges in most of the slides from control cases, regardless of the staining methods that were used. Moreover, none of the tested method or staining pattern had a specificity and sensitivity more than 80 % regarding to PD. Overall, our study suggest that the tested methods are not adequate for the prediction of PD using gastrointestinal biopsies. Future studies are warranted to test new immunostaining methods

Revisiting the Higgs Mass and Dark Matter in the CMSSM

Taking into account the available accelerator and astrophysical constraints, the mass of the lightest neutral Higgs boson h in the minimal supersymmetric extension of the Standard Model with universal soft supersymmetry-breaking masses (CMSSM) has been estimated to lie between 114 and ~ 130 GeV. Recent data from ATLAS and CMS hint that m_h ~ 125 GeV, though m_h ~ 119 GeV may still be a possibility. Here we study the consequences for the parameters of the CMSSM and direct dark matter detection if the Higgs hint is confirmed, focusing on the strips in the (m_1/2, m_0) planes for different tan beta and A_0 where the relic density of the lightest neutralino chi falls within the range of the cosmological cold dark matter density allowed by WMAP and other experiments. We find that if m_h ~ 125 GeV focus-point strips would be disfavoured, as would the low-tan beta stau-chi and stop -chi coannihilation strips, whereas the stau-chi coannihilation strip at large tan beta and A_0 > 0 would be favoured, together with its extension to a funnel where rapid annihilation via direct-channel H/A poles dominates. On the other hand, if m_h ~ 119 GeV more options would be open. We give parametrizations of WMAP strips with large tan beta and fixed A_0/m_0 > 0 that include portions compatible with m_h = 125 GeV, and present predictions for spin-independent elastic dark matter scattering along these strips. These are generally low for models compatible with m_h = 125 GeV, whereas the XENON100 experiment already excludes some portions of strips where m_h is smaller.Comment: 24 pages, 9 figure

Colliders and Cosmology

Dark matter in variations of constrained minimal supersymmetric standard models will be discussed. Particular attention will be given to the comparison between accelerator and direct detection constraints.Comment: Submitted for the SUSY07 proceedings, 15 pages, LaTex, 26 eps figure

Likelihood Functions for Supersymmetric Observables in Frequentist Analyses of the CMSSM and NUHM1

On the basis of frequentist analyses of experimental constraints from electroweak precision data, g-2, B physics and cosmological data, we investigate the parameters of the constrained MSSM (CMSSM) with universal soft supersymmetry-breaking mass parameters, and a model with common non-universal Higgs masses (NUHM1). We present chi^2 likelihood functions for the masses of supersymmetric particles and Higgs bosons, as well as b to s gamma, b to mu mu and the spin-independent dark matter scattering cross section. In the CMSSM we find preferences for sparticle masses that are relatively light. In the NUHM1 the best-fit values for many sparticle masses are even slightly smaller, but with greater uncertainties. The likelihood functions for most sparticle masses are cut off sharply at small masses, in particular by the LEP Higgs mass constraint. Both in the CMSSM and the NUHM1, the coannihilation region is favoured over the focus-point region at about the 3-sigma level, largely but not exclusively because of g-2. Many sparticle masses are highly correlated in both the CMSSM and NUHM1, and most of the regions preferred at the 95% C.L. are accessible to early LHC running. Some slepton and chargino/neutralino masses should be in reach at the ILC. The masses of the heavier Higgs bosons should be accessible at the LHC and the ILC in portions of the preferred regions in the (M_A, tan beta) plane. In the CMSSM, the likelihood function for b to mu mu is peaked close to the Standard Model value, but much larger values are possible in the NUHM1. We find that values of the DM cross section > 10^{-10} pb are preferred in both the CMSSM and the NUHM1. We study the effects of dropping the g-2, b to s gamma, relic density and M_h constraints.Comment: 34 pages, 24 figure

Lifetimes of High-Degree p Modes in the Quiet and Active Sun

We study variations of the lifetimes of high-degree solar p-modes in the quiet and active Sun with the solar activity cycle. The lifetimes in the degree range 300 - 600 and frequency 2.5 - 4.5 mHz were computed from SOHO/MDI data in an area including active regions and quiet Sun using the time-distance technique. We applied our analysis to the data in four different phases of solar activity: in 1996 (at minimum), 1998 (rising phase), 2000 (at maximum) and 2003 (declining phase). The results from the area with active regions show that the lifetime decreases as activity increases. The maximal lifetime variations are between solar minimum in 1996 and maximum in 2000; the relative variation averaged over all mode degree values and frequencies is a decrease of about 13%. The lifetime reductions relative to 1996 are about 7% in 1998 and about 10% in 2003. The lifetime computed in the quiet region still decreases with solar activity although the decrease is smaller. On average, relative to 1996, the lifetime decrease is about 4% in 1998, 10% in 2000 and 8% in 2003. Thus, measured lifetime increases when regions of high magnetic activity are avoided. Moreover, the lifetime computed in quiet regions also shows variations with activity cycle.Comment: 13 pages, 5 figures; Accepted for publication in Solar Physic

Prognostic factors of a lower CD4/CD8 ratio in long term viral suppression HIV infected children

Background Combination antiretroviral therapy (cART) is associated with marked immune reconstitution. Although a long term viral suppression is achievable, not all children however, attain complete immunological recovery due to persistent immune activation. We use CD4/CD8 ratio like a marker of immune reconstitution. Methods Perinatal HIV-infected children who underwent a first-line cART, achieved viral suppression in the first year and maintained it for more than 5 years, with no viral rebound were included. Logistic models were applied to estimate the prognostic factors, clinical characteristics at cART start, of a lower CD4/CD8 ratio at the last visit. Results 146 HIV-infected children were included: 77% Caucasian, 45% male and 28% CDC C. Median age at cART initiation was 2.3 years (IQR: 0.5-6.2). 42 (30%) children received mono-dual therapy previously to cART. Time of undetectable viral load was 9.5 years (IQR: 7.8, 12.5). 33% of the children not achieved CD4/CD8 ratio >1. Univariate analysis showed an association between CD4/CD8 <1 with lower CD4 nadir and baseline CD4; older age at diagnosis and at cART initiation; and a previous exposure to mono-dual therapy. Multivariate analysis also revealed relationship between CD4/CD8 <1 and lower CD4 nadir (OR: 1.002, CI 95% 1.000-1.004) as well as previous exposure to mono-dual therapy (OR: 0.16, CI 95% 0.003-0.720). Conclusions CD4/CD8 > 1 was not achieved in 33% of the children. Lower CD4 nadir and previous exposure to suboptimal therapy, before initiating cART, are factors showing independently association with a worse immune recovery (CD4/CD8 < 1)

The LEGA-C survey completed: stellar populations and stellar kinematics of galaxies 7 Gyr ago

Galaxie

Whole genome analysis of a schistosomiasis-transmitting freshwater snail

Biomphalaria snails are instrumental in transmission of the human blood fluke Schistosoma mansoni. With the World Health Organization's goal to eliminate schistosomiasis as a global health problem by 2025, there is now renewed emphasis on snail control. Here, we characterize the genome of Biomphalaria glabrata, a lophotrochozoan protostome, and provide timely and important information on snail biology. We describe aspects of phero-perception, stress responses, immune function and regulation of gene expression that support the persistence of B. glabrata in the field and may define this species as a suitable snail host for S. mansoni. We identify several potential targets for developing novel control measures aimed at reducing snail-mediated transmission of schistosomiasis

Immunohistochemical Method and Histopathology Judging for the Systemic Synuclein Sampling Study (S4)

Immunohistochemical (IHC) α-synuclein (Asyn) pathology in peripheral biopsies may be a biomarker of Parkinson disease (PD). The multi-center Systemic Synuclein Sampling Study (S4) is evaluating IHC Asyn pathology within skin, colon and submandibular gland biopsies from 60 PD and 20 control subjects. Asyn pathology is being evaluated by a blinded panel of specially trained neuropathologists. Preliminary work assessed 2 candidate immunoperoxidase methods using a set of PD and control autopsy-derived sections from formalin-fixed, paraffin-embedded blocks of the 3 tissues. Both methods had 100% specificity; one, utilizing the 5C12 monoclonal antibody, was more sensitive in skin (67% vs 33%), and was chosen for further use in S4. Four trainee neuropathologists were trained to perform S4 histopathology readings; in subsequent testing, their scoring was compared to that of the trainer neuropathologist on both glass slides and digital images. Specificity and sensitivity were both close to 100% with all readers in all tissue types on both glass slides and digital images except for skin, where sensitivity averaged 75% with digital images and 83.5% with glass slides. Semiquantitative (0-3) density score agreement between trainees and trainer averaged 67% for glass slides and 62% for digital images