Association Between Lifetime Marijuana Use and Cognitive Function in Middle Age: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

Marijuana use is increasingly common in the United States. It is unclear whether it has long-term effects on memory and other domains of cognitive function. To study the association between cumulative lifetime exposure to marijuana use and cognitive performance in middle age. We used data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a cohort of 5115 black and white men and women aged 18 to 30 years at baseline from March 25, 1985, to June 7, 1986 (year 0), and followed up over 25 years from June 7, 1986, to August 31, 2011, to estimate cumulative years of exposure to marijuana (1 year = 365 days of marijuana use) using repeated measures and to assess associations with cognitive function at year 25. Linear regression was used to adjust for demographic factors, cardiovascular risk factors, tobacco smoking, use of alcohol and illicit drugs, physical activity, depression, and results of the mirror star tracing test (a measure of cognitive function) at year 2. Data analysis was conducted from June 7, 1986, to August 31, 2011. Three domains of cognitive function were assessed at year 25 using the Rey Auditory Verbal Learning Test (verbal memory), the Digit Symbol Substitution Test (processing speed), and the Stroop Interference Test (executive function). Among 3385 participants with cognitive function measurements at the year 25 visit, 2852 (84.3%) reported past marijuana use, but only 392 (11.6%) continued to use marijuana into middle age. Current use of marijuana was associated with worse verbal memory and processing speed; cumulative lifetime exposure was associated with worse performance in all 3 domains of cognitive function. After excluding current users and adjusting for potential confounders, cumulative lifetime exposure to marijuana remained significantly associated with worse verbal memory. For each 5 years of past exposure, verbal memory was 0.13 standardized units lower (95% CI, -0.24 to -0.02; P = .02), corresponding to a mean of 1 of 2 participants remembering 1 word fewer from a list of 15 words for every 5 years of use. After adjustment, we found no associations with lower executive function (-0.03 [95% CI, -0.12 to 0.07]; P = .56) or processing speed (-0.04 [95% CI, -0.16 to 0.08]; P = .51). Past exposure to marijuana is associated with worse verbal memory but does not appear to affect other domains of cognitive function

Quantifying positional isomers (QPI) by top-down mass spectrometry

Proteomics has exposed a plethora of posttranslational modifications, but demonstrating functional relevance requires new approaches. Top-down proteomics of intact proteins has the potential to fully characterize protein modifications in terms of amount, site(s), and the order in which they are deposited on the protein; information that so far has been elusive to extract by shotgun proteomics. Data acquisition and analysis of intact multimodified proteins have however been a major challenge, in particular for positional isomers that carry the same number of modifications at different sites. Solutions were previously proposed to extract this information from fragmentation spectra, but these have so far mainly been limited to peptides and have entailed a large degree of manual interpretation. Here, we apply high-resolution Orbitrap fusion top-down analyses in combination with bioinformatics approaches to attempt to characterize multiple modified proteins and quantify positional isomers. Automated covalent fragment ion type definition, detection of mass precision and accuracy, and extensive use of replicate spectra increase sequence coverage and drive down false fragment assignments from 10% to 1.5%. Such improved performance in fragment assignment is key to localize and quantify modifications from fragment spectra. The method is tested by investigating positional isomers of Ubiquitin mixed in known concentrations, which results in quantification of high ratios at very low standard errors of the mean (<5%), as well as with synthetic phosphorylated peptides. Application to multiphosphorylated Bora provides an estimation of the so far unknown stoichiometry of the known set of phosphosites and uncovers new sites from hyperphosphorylated Bora.Chemical Immunolog

Perspectives on metaphyseal conservative stems

Total hip replacement is showing, during the last decades, a progressive evolution toward principles of reduced bone and soft tissue aggression. These principles have become the basis of a new philosophy, tissue sparing surgery. Regarding hip implants, new conservative components have been proposed and developed as an alternative to conventional stems. Technical and biomechanical characteristics of metaphyseal bone-stock-preserving stems are analyzed on the basis of the available literature and our personal experience. Mayo, Nanos and Metha stems represent, under certain aspects, a design evolution starting from shared concepts: reduced femoral violation, non-anatomic geometry, proximal calcar loading and lateral alignment. However, consistent differences are level of neck preservation, cross-sectional geometry and surface finishing. The Mayo component is the most time-tested component and, in our hands, it showed an excellent survivorship at the mid-term follow-up, with an extremely reduced incidence of aseptic loosening (partially reduced by the association with last generation acetabular couplings). For 160 implants followed for a mean of 4.7 years, survivorship was 97.5% with 4 failed implants: one fracture with unstable stem, 1 septic loosening and 2 aseptic mobilizations. DEXA analysis, performed on 15 cases, showed a good calcar loading and stimulation, but there was significant lateral load transfer to R3–R4 zones, giving to the distal part of the stem a function not simply limited to alignment. Metaphyseal conservative stems demonstrated a wide applicability with an essential surgical technique. Moreover, they offer the options of a “conservative revision” with a conventional primary component in case of failure and a “conservative revision” for failed resurfacing implants

The spectral gap for some spin chains with discrete symmetry breaking

We prove that for any finite set of generalized valence bond solid (GVBS) states of a quantum spin chain there exists a translation invariant finite-range Hamiltonian for which this set is the set of ground states. This result implies that there are GVBS models with arbitrary broken discrete symmetries that are described as combinations of lattice translations, lattice reflections, and local unitary or anti-unitary transformations. We also show that all GVBS models that satisfy some natural conditions have a spectral gap. The existence of a spectral gap is obtained by applying a simple and quite general strategy for proving lower bounds on the spectral gap of the generator of a classical or quantum spin dynamics. This general scheme is interesting in its own right and therefore, although the basic idea is not new, we present it in a system-independent setting. The results are illustrated with an number of examples.Comment: 48 pages, Plain TeX, BN26/Oct/9

Deconfining Phase Transition as a Matrix Model of Renormalized Polyakov Loops

We discuss how to extract renormalized from bare Polyakov loops in SU(N) lattice gauge theories at nonzero temperature in four spacetime dimensions. Single loops in an irreducible representation are multiplicatively renormalized without mixing, through a renormalization constant which depends upon both representation and temperature. The values of renormalized loops in the four lowest representations of SU(3) were measured numerically on small, coarse lattices. We find that in magnitude, condensates for the sextet and octet loops are approximately the square of the triplet loop. This agrees with a large $N$ expansion, where factorization implies that the expectation values of loops in adjoint and higher representations are just powers of fundamental and anti-fundamental loops. For three colors, numerically the corrections to the large $N$ relations are greatest for the sextet loop, $\leq 25$; these represent corrections of $\sim 1/N$ for N=3. The values of the renormalized triplet loop can be described by an SU(3) matrix model, with an effective action dominated by the triplet loop. In several ways, the deconfining phase transition for N=3 appears to be like that in the $N=\infty$ matrix model of Gross and Witten.Comment: 24 pages, 7 figures; v2, 27 pages, 12 figures, extended discussion for clarity, results unchange

SND@LHC: The Scattering and Neutrino Detector at the LHC

SND@LHC is a compact and stand-alone experiment designed to perform measurements with neutrinos produced at the LHC in the pseudo-rapidity region of ${7.2 < \eta < 8.4}$. The experiment is located 480 m downstream of the ATLAS interaction point, in the TI18 tunnel. The detector is composed of a hybrid system based on an 830 kg target made of tungsten plates, interleaved with emulsion and electronic trackers, also acting as an electromagnetic calorimeter, and followed by a hadronic calorimeter and a muon identification system. The detector is able to distinguish interactions of all three neutrino flavours, which allows probing the physics of heavy flavour production at the LHC in the very forward region. This region is of particular interest for future circular colliders and for very high energy astrophysical neutrino experiments. The detector is also able to search for the scattering of Feebly Interacting Particles. In its first phase, the detector will operate throughout LHC Run 3 and collect a total of 250 $\text{fb}^{-1}$

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

Relationship of edge localized mode burst times with divertor flux loop signal phase in JET

A phase relationship is identified between sequential edge localized modes (ELMs) occurrence times in a set of H-mode tokamak plasmas to the voltage measured in full flux azimuthal loops in the divertor region. We focus on plasmas in the Joint European Torus where a steady H-mode is sustained over several seconds, during which ELMs are observed in the Be II emission at the divertor. The ELMs analysed arise from intrinsic ELMing, in that there is no deliberate intent to control the ELMing process by external means. We use ELM timings derived from the Be II signal to perform direct time domain analysis of the full flux loop VLD2 and VLD3 signals, which provide a high cadence global measurement proportional to the voltage induced by changes in poloidal magnetic flux. Specifically, we examine how the time interval between pairs of successive ELMs is linked to the time-evolving phase of the full flux loop signals. Each ELM produces a clear early pulse in the full flux loop signals, whose peak time is used to condition our analysis. The arrival time of the following ELM, relative to this pulse, is found to fall into one of two categories: (i) prompt ELMs, which are directly paced by the initial response seen in the flux loop signals; and (ii) all other ELMs, which occur after the initial response of the full flux loop signals has decayed in amplitude. The times at which ELMs in category (ii) occur, relative to the first ELM of the pair, are clustered at times when the instantaneous phase of the full flux loop signal is close to its value at the time of the first ELM

Measurement of the muon flux from 400 GeV/c protons interacting in a thick molybdenum/tungsten target

The SHiP experiment is proposed to search for very weakly interacting particles beyond the Standard Model which are produced in a 400 GeV/c proton beam dump at the CERN SPS. About 1011 muons per spill will be produced in the dump. To design the experiment such that the muon-induced background is minimized, a precise knowledge of the muon spectrum is required. To validate the muon flux generated by our Pythia and GEANT4 based Monte Carlo simulation (FairShip), we have measured the muon flux emanating from a SHiP-like target at the SPS. This target, consisting of 13 interaction lengths of slabs of molybdenum and tungsten, followed by a 2.4 m iron hadron absorber was placed in the H4 400 GeV/c proton beam line. To identify muons and to measure the momentum spectrum, a spectrometer instrumented with drift tubes and a muon tagger were used. During a 3-week period a dataset for analysis corresponding to (3.27±0.07) × 1011 protons on target was recorded. This amounts to approximatively 1% of a SHiP spill