Search for magnetic monopoles produced via the Schwinger mechanism.

Electrically charged particles can be created by the decay of strong enough electric fields, a phenomenon known as the Schwinger mechanism1. By electromagnetic duality, a sufficiently strong magnetic field would similarly produce magnetic monopoles, if they exist2. Magnetic monopoles are hypothetical fundamental particles that are predicted by several theories beyond the standard model3-7 but have never been experimentally detected. Searching for the existence of magnetic monopoles via the Schwinger mechanism has not yet been attempted, but it is advantageous, owing to the possibility of calculating its rate through semi-classical techniques without perturbation theory, as well as that the production of the magnetic monopoles should be enhanced by their finite size8,9 and strong coupling to photons2,10. Here we present a search for magnetic monopole production by the Schwinger mechanism in Pb-Pb heavy ion collisions at the Large Hadron Collider, producing the strongest known magnetic fields in the current Universe11. It was conducted by the MoEDAL experiment, whose trapping detectors were exposed to 0.235 per nanobarn, or approximately 1.8 × 109, of Pb-Pb collisions with 5.02-teraelectronvolt center-of-mass energy per collision in November 2018. A superconducting quantum interference device (SQUID) magnetometer scanned the trapping detectors of MoEDAL for the presence of magnetic charge, which would induce a persistent current in the SQUID. Magnetic monopoles with integer Dirac charges of 1, 2 and 3 and masses up to 75 gigaelectronvolts per speed of light squared were excluded by the analysis at the 95% confidence level. This provides a lower mass limit for finite-size magnetic monopoles from a collider search and greatly extends previous mass bounds.

First Search for Dyons with the Full MoEDAL Trapping Detector in 13 TeV pp Collisions.

The MoEDAL trapping detector consists of approximately 800 kg of aluminum volumes. It was exposed during run 2 of the LHC program to 6.46 fb^{-1} of 13 TeV proton-proton collisions at the LHCb interaction point. Evidence for dyons (particles with electric and magnetic charge) captured in the trapping detector was sought by passing the aluminum volumes comprising the detector through a superconducting quantum interference device (SQUID) magnetometer. The presence of a trapped dyon would be signaled by a persistent current induced in the SQUID magnetometer. On the basis of a Drell-Yan production model, we exclude dyons with a magnetic charge ranging up to five Dirac charges (5g_{D}) and an electric charge up to 200 times the fundamental electric charge for mass limits in the range 870-3120 GeV and also monopoles with magnetic charge up to and including 5g_{D} with mass limits in the range 870-2040 GeV.

Magnetic Monopole Search with the Full MoEDAL Trapping Detector in 13 TeV pp Collisions Interpreted in Photon-Fusion and Drell-Yan Production.

MoEDAL is designed to identify new physics in the form of stable or pseudostable highly ionizing particles produced in high-energy Large Hadron Collider (LHC) collisions. Here we update our previous search for magnetic monopoles in Run 2 using the full trapping detector with almost four times more material and almost twice more integrated luminosity. For the first time at the LHC, the data were interpreted in terms of photon-fusion monopole direct production in addition to the Drell-Yan-like mechanism. The MoEDAL trapping detector, consisting of 794 kg of aluminum samples installed in the forward and lateral regions, was exposed to 4.0 fb^{-1} of 13 TeV proton-proton collisions at the LHCb interaction point and analyzed by searching for induced persistent currents after passage through a superconducting magnetometer. Magnetic charges equal to or above the Dirac charge are excluded in all samples. Monopole spins 0, ½, and 1 are considered and both velocity-independent and-dependent couplings are assumed. This search provides the best current laboratory constraints for monopoles with magnetic charges ranging from two to five times the Dirac charge.

At-vessel mortality of skates (Rajidae) taken in coastal fisheries and evidence of longer-term survival.

Data on the vigour and at-vessel mortality (AVM) of 6798 skates (comprising Raja clavata n = 6295; R. brachyura n = 208; R. undulata n = 185, R. montagui n = 98 and R. microocellata n = 12) captured by commercial fishing vessels in the inshore waters of the southern North Sea and English Channel were recorded. AVM in longline fisheries averaged 0·44% across five vessels (0-1·47%), although skates were usually unhooked manually and did not usually pass through a bait-stripper. AVM in otter trawls averaged 0·76% (0-2·35%), from four vessels fishing with tow durations of <1·5 h (southern North Sea) or 1-4 h (English Channel). No AVM was noted for skates taken as a by-catch in drift trammel nets (soak times <4 h). Anchored tangle nets resulted in an overall AVM of 2·0-2·7%, but increased from 1·47% (13-28 h soak time) to 6·16% (42-53 h soak time). There were significant differences in the vigour of skates between gears, with R. clavata caught by longline and tangle nets in better condition than those captured by otter trawl or drift trammel net. Similarly, R. undulata caught by tangle net were in better condition than those caught by otter trawl. The vigour of R. undulata was also found to be higher than other skate species for both trawl and tangle net. In total, 5283 skates were tagged with Petersen discs and released, with recapture rates for the various combinations of vessel and gear ranging up to 24·8% for R. clavata. Whilst confirming a degree of post-release survival, quantitative estimates of post-release mortality for skates remain unknown.

Likelihood analysis of the pMSSM11 in light of LHC 13-TeV data.

We use MasterCode to perform a frequentist analysis of the constraints on a phenomenological MSSM model with 11 parameters, the pMSSM11, including constraints from ∼ 36 /fb of LHC data at 13 TeV and PICO, XENON1T and PandaX-II searches for dark matter scattering, as well as previous accelerator and astrophysical measurements, presenting fits both with and without the ( g - 2 ) µ constraint. The pMSSM11 is specified by the following parameters: 3 gaugino masses M 1 , 2 , 3 , a common mass for the first-and second-generation squarks m q ~ and a distinct third-generation squark mass m q ~ 3 , a common mass for the first-and second-generation sleptons m ℓ ~ and a distinct third-generation slepton mass m τ ~ , a common trilinear mixing parameter A, the Higgs mixing parameter µ , the pseudoscalar Higgs mass M A and tan ß . In the fit including ( g - 2 ) µ , a Bino-like χ ~ 1 0 is preferred, whereas a Higgsino-like χ ~ 1 0 is mildly favoured when the ( g - 2 ) µ constraint is dropped. We identify the mechanisms that operate in different regions of the pMSSM11 parameter space to bring the relic density of the lightest neutralino, χ ~ 1 0 , into the range indicated by cosmological data. In the fit including ( g - 2 ) µ , coannihilations with χ ~ 2 0 and the Wino-like χ ~ 1 ± or with nearly-degenerate first- and second-generation sleptons are active, whereas coannihilations with the χ ~ 2 0 and the Higgsino-like χ ~ 1 ± or with first- and second-generation squarks may be important when the ( g - 2 ) µ constraint is dropped. In the two cases, we present χ 2 functions in two-dimensional mass planes as well as their one-dimensional profile projections and best-fit spectra. Prospects remain for discovering strongly-interacting sparticles at the LHC, in both the scenarios with and without the ( g - 2 ) µ constraint, as well as for discovering electroweakly-interacting sparticles at a future linear e + e - collider such as the ILC or CLIC.

Likelihood analysis of the minimal AMSB model.

We perform a likelihood analysis of the minimal anomaly-mediated supersymmetry-breaking (mAMSB) model using constraints from cosmology and accelerator experiments. We find that either a wino-like or a Higgsino-like neutralino LSP, [Formula: see text], may provide the cold dark matter (DM), both with similar likelihoods. The upper limit on the DM density from Planck and other experiments enforces [Formula: see text] after the inclusion of Sommerfeld enhancement in its annihilations. If most of the cold DM density is provided by the [Formula: see text], the measured value of the Higgs mass favours a limited range of [Formula: see text] (and also for [Formula: see text] if [Formula: see text]) but the scalar mass [Formula: see text] is poorly constrained. In the wino-LSP case, [Formula: see text] is constrained to about [Formula: see text] and [Formula: see text] to [Formula: see text], whereas in the Higgsino-LSP case [Formula: see text] has just a lower limit [Formula: see text] ([Formula: see text]) and [Formula: see text] is constrained to [Formula: see text] in the [Formula: see text] ([Formula: see text]) scenario. In neither case can the anomalous magnetic moment of the muon, [Formula: see text], be improved significantly relative to its Standard Model (SM) value, nor do flavour measurements constrain the model significantly, and there are poor prospects for discovering supersymmetric particles at the LHC, though there are some prospects for direct DM detection. On the other hand, if the [Formula: see text] contributes only a fraction of the cold DM density, future LHC [Formula: see text]-based searches for gluinos, squarks and heavier chargino and neutralino states as well as disappearing track searches in the wino-like LSP region will be relevant, and interference effects enable [Formula: see text] to agree with the data better than in the SM in the case of wino-like DM with [Formula: see text].

Likelihood analysis of supersymmetric SU(5) GUTs.

We perform a likelihood analysis of the constraints from accelerator experiments and astrophysical observations on supersymmetric (SUSY) models with SU(5) boundary conditions on soft SUSY-breaking parameters at the GUT scale. The parameter space of the models studied has seven parameters: a universal gaugino mass [Formula: see text], distinct masses for the scalar partners of matter fermions in five- and ten-dimensional representations of SU(5), [Formula: see text] and [Formula: see text], and for the [Formula: see text] and [Formula: see text] Higgs representations [Formula: see text] and [Formula: see text], a universal trilinear soft SUSY-breaking parameter [Formula: see text], and the ratio of Higgs vevs [Formula: see text]. In addition to previous constraints from direct sparticle searches, low-energy and flavour observables, we incorporate constraints based on preliminary results from 13 TeV LHC searches for jets + [Formula: see text] events and long-lived particles, as well as the latest PandaX-II and LUX searches for direct Dark Matter detection. In addition to previously identified mechanisms for bringing the supersymmetric relic density into the range allowed by cosmology, we identify a novel [Formula: see text] coannihilation mechanism that appears in the supersymmetric SU(5) GUT model and discuss the role of [Formula: see text] coannihilation. We find complementarity between the prospects for direct Dark Matter detection and SUSY searches at the LHC.

Search for Magnetic Monopoles with the MoEDAL Forward Trapping Detector in 13 TeV Proton-Proton Collisions at the LHC.

MoEDAL is designed to identify new physics in the form of long-lived highly ionizing particles produced in high-energy LHC collisions. Its arrays of plastic nuclear-track detectors and aluminium trapping volumes provide two independent passive detection techniques. We present here the results of a first search for magnetic monopole production in 13 TeV proton-proton collisions using the trapping technique, extending a previous publication with 8 TeV data during LHC Run 1. A total of 222 kg of MoEDAL trapping detector samples was exposed in the forward region and analyzed by searching for induced persistent currents after passage through a superconducting magnetometer. Magnetic charges exceeding half the Dirac charge are excluded in all samples and limits are placed for the first time on the production of magnetic monopoles in 13 TeV pp collisions. The search probes mass ranges previously inaccessible to collider experiments for up to five times the Dirac charge.

A review of capture and post-release mortality of elasmobranchs.

There is a need to better understand the survivorship of discarded fishes, both for commercial stocks and species of conservation concern. Within European waters, the landing obligations that are currently being phased in as part of the European Union's reformed common fisheries policy means that an increasing number of fish stocks, with certain exceptions, should not be discarded unless it can be demonstrated that there is a high probability of survival. This study reviews the various approaches that have been used to examine the discard survival of elasmobranchs, both in terms of at-vessel mortality (AVM) and post-release mortality (PRM), with relevant findings summarized for both the main types of fishing gear used and by taxonomic group. Discard survival varies with a range of biological attributes (species, size, sex and mode of gill ventilation) as well as the range of factors associated with capture (e.g. gear type, soak time, catch mass and composition, handling practices and the degree of exposure to air and any associated change in ambient temperature). In general, demersal species with buccal-pump ventilation have a higher survival than obligate ram ventilators. Several studies have indicated that females may have a higher survival than males. Certain taxa (including hammerhead sharks Sphyrna spp. and thresher sharks Alopias spp.) may be particularly prone to higher rates of mortality when caught.

Reproductive characteristics and life-history relationships of starry smooth-hound Mustelus asterias in British waters.

The reproductive biology and other life-history parameters were investigated for Mustelus asterias in British waters, with specimens caught from both commercial fisheries and research-vessel surveys. In total, 504 specimens [238 males, 24-99 cm total length (LT) and 266 females, 28-124 cm LT] were examined, with further information collected from 238 uterine pups. The lengths at 50% maturity were estimated as 70·4 and 81·9 cm LT for males and females, respectively. Ovarian fecundity ranged from one to 28, and uterine fecundity from four to 20. The number, mass and LT of pups were positively correlated with maternal LT. Full-term pups ranged from 205 to 329 mm LT, and the smallest free-living fish caught was 24 cm LT . Parturition occurred in February in the western English Channel and during June to July in the eastern English Channel and southern North Sea, indicating either protracted spawning or asynchronous parturition for the stock as a whole. The reproductive cycle is thought to extend beyond 1 year. Developmental abnormalities observed included atresia in oocytes, uterine eggs that failed to develop, a partly developed pup and an abnormal male with a single aberrant clasper. Data relating to conversion factors, oocyte numbers and diameter and gonado-somatic and hepato-somatic indices are presented, and the seasonality of the reproductive cycle is discussed.

Supersymmetric dark matter after LHC run 1.

Different mechanisms operate in various regions of the MSSM parameter space to bring the relic density of the lightest neutralino, [Formula: see text], assumed here to be the lightest SUSY particle (LSP) and thus the dark matter (DM) particle, into the range allowed by astrophysics and cosmology. These mechanisms include coannihilation with some nearly degenerate next-to-lightest supersymmetric particle such as the lighter stau [Formula: see text], stop [Formula: see text] or chargino [Formula: see text], resonant annihilation via direct-channel heavy Higgs bosons H / A, the light Higgs boson h or the Z boson, and enhanced annihilation via a larger Higgsino component of the LSP in the focus-point region. These mechanisms typically select lower-dimensional subspaces in MSSM scenarios such as the CMSSM, NUHM1, NUHM2, and pMSSM10. We analyze how future LHC and direct DM searches can complement each other in the exploration of the different DM mechanisms within these scenarios. We find that the [Formula: see text] coannihilation regions of the CMSSM, NUHM1, NUHM2 can largely be explored at the LHC via searches for [Formula: see text] events and long-lived charged particles, whereas their H / A funnel, focus-point and [Formula: see text] coannihilation regions can largely be explored by the LZ and Darwin DM direct detection experiments. We find that the dominant DM mechanism in our pMSSM10 analysis is [Formula: see text] coannihilation: parts of its parameter space can be explored by the LHC, and a larger portion by future direct DM searches.

The pMSSM10 after LHC run 1.

We present a frequentist analysis of the parameter space of the pMSSM10, in which the following ten soft SUSY-breaking parameters are specified independently at the mean scalar top mass scale [Formula: see text]: the gaugino masses [Formula: see text], the first-and second-generation squark masses [Formula: see text], the third-generation squark mass [Formula: see text], a common slepton mass [Formula: see text] and a common trilinear mixing parameter A, as well as the Higgs mixing parameter [Formula: see text], the pseudoscalar Higgs mass [Formula: see text] and [Formula: see text], the ratio of the two Higgs vacuum expectation values. We use the MultiNest sampling algorithm with [Formula: see text]1.2 [Formula: see text] points to sample the pMSSM10 parameter space. A dedicated study shows that the sensitivities to strongly interacting sparticle masses of ATLAS and CMS searches for jets, leptons [Formula: see text][Formula: see text] signals depend only weakly on many of the other pMSSM10 parameters. With the aid of the Atom and Scorpion codes, we also implement the LHC searches for electroweakly interacting sparticles and light stops, so as to confront the pMSSM10 parameter space with all relevant SUSY searches. In addition, our analysis includes Higgs mass and rate measurements using the HiggsSignals code, SUSY Higgs exclusion bounds, the measurements of [Formula: see text] by LHCb and CMS, other B-physics observables, electroweak precision observables, the cold dark matter density and the XENON100 and LUX searches for spin-independent dark matter scattering, assuming that the cold dark matter is mainly provided by the lightest neutralino [Formula: see text]. We show that the pMSSM10 is able to provide a supersymmetric interpretation of [Formula: see text], unlike the CMSSM, NUHM1 and NUHM2. As a result, we find (omitting Higgs rates) that the minimum [Formula: see text] with 18 degrees of freedom (d.o.f.) in the pMSSM10, corresponding to a [Formula: see text] probability of 30.8 %, to be compared with [Formula: see text] in the CMSSM (NUHM1) (NUHM2). We display the one-dimensional likelihood functions for sparticle masses, and we show that they may be significantly lighter in the pMSSM10 than in the other models, e.g., the gluino may be as light as [Formula: see text]1250 [Formula: see text] at the 68 % CL, and squarks, stops, electroweak gauginos and sleptons may be much lighter than in the CMSSM, NUHM1 and NUHM2. We discuss the discovery potential of future LHC runs, [Formula: see text] colliders and direct detection experiments.

Angular roughshark Oxynotus centrina (Squaliformes: Oxynotidae) in captivity feeding exclusively on elasmobranch eggs: an overlooked feeding niche or a matter of individual taste?

A specimen of angular roughshark Oxynotus centrina has been kept successfully in captivity for the first time. Over a period of 24 months, the specimen preyed exclusively on the contents of elasmobranch egg cases, suggesting a specialized trophic niche.

The NUHM2 after LHC Run 1.

We make a frequentist analysis of the parameter space of the NUHM2, in which the soft supersymmetry (SUSY)-breaking contributions to the masses of the two Higgs multiplets, [Formula: see text], vary independently from the universal soft SUSY-breaking contributions [Formula: see text] to the masses of squarks and sleptons. Our analysis uses the MultiNest sampling algorithm with over [Formula: see text] points to sample the NUHM2 parameter space. It includes the ATLAS and CMS Higgs mass measurements as well as the ATLAS search for supersymmetric jets + [Formula: see text] signals using the full LHC Run 1 data, the measurements of [Formula: see text] by LHCb and CMS together with other B-physics observables, electroweak precision observables and the XENON100 and LUX searches for spin-independent dark-matter scattering. We find that the preferred regions of the NUHM2 parameter space have negative SUSY-breaking scalar masses squared at the GUT scale for squarks and sleptons, [Formula: see text], as well as [Formula: see text]. The tension present in the CMSSM and NUHM1 between the supersymmetric interpretation of [Formula: see text] and the absence to date of SUSY at the LHC is not significantly alleviated in the NUHM2. We find that the minimum [Formula: see text] with 21 degrees of freedom (dof) in the NUHM2, to be compared with [Formula: see text] in the CMSSM, and [Formula: see text] in the NUHM1. We find that the one-dimensional likelihood functions for sparticle masses and other observables are similar to those found previously in the CMSSM and NUHM1.

The CMSSM and NUHM1 after LHC Run 1.

We analyze the impact of data from the full Run 1 of the LHC at 7 and 8 TeV on the CMSSM with [Formula: see text] and [Formula: see text] and the NUHM1 with [Formula: see text], incorporating the constraints imposed by other experiments such as precision electroweak measurements, flavour measurements, the cosmological density of cold dark matter and the direct search for the scattering of dark matter particles in the LUX experiment. We use the following results from the LHC experiments: ATLAS searches for events with [Formula: see text] accompanied by jets with the full 7 and 8 TeV data, the ATLAS and CMS measurements of the mass of the Higgs boson, the CMS searches for heavy neutral Higgs bosons and a combination of the LHCb and CMS measurements of [Formula: see text] and [Formula: see text]. Our results are based on samplings of the parameter spaces of the CMSSM for both [Formula: see text] and [Formula: see text] and of the NUHM1 for [Formula: see text] with 6.8[Formula: see text], 6.2[Formula: see text] and 1.6[Formula: see text] points, respectively, obtained using the MultiNest tool. The impact of the Higgs-mass constraint is assessed using FeynHiggs 2.10.0, which provides an improved prediction for the masses of the MSSM Higgs bosons in the region of heavy squark masses. It yields in general larger values of [Formula: see text] than previous versions of FeynHiggs, reducing the pressure on the CMSSM and NUHM1. We find that the global [Formula: see text] functions for the supersymmetric models vary slowly over most of the parameter spaces allowed by the Higgs-mass and the [Formula: see text] searches, with best-fit values that are comparable to the [Formula: see text] for the best Standard Model fit. We provide 95 % CL lower limits on the masses of various sparticles and assess the prospects for observing them during Run 2 of the LHC.

An ex vivo investigation of the effect of the TATE canine elbow arthroplasty system on kinematics of the elbow.

OBJECTIVE: To devise a kinematic technique to objectively ascertain the location and orientation of the centre of rotation of the canine elbow and to compare this axis following arthroplasty with the first generation TATE™ prosthesis in an ex vivo model. METHODS: Five pairs of cadaveric forelimbs were obtained and proximal limb soft tissues removed. Pin-mounted reflective markers were applied to the humerus and ulna. Limbs were mounted on a frame and six trials of the elbow manually cycled through its sagittal range of motion captured using 4 Qualisys cameras at 120 Hz. Radiography was performed to identify marker position. TATE™ cartridges were implanted and kinematic analysis repeated. Kinematic data were imported into custom software and the three-dimensional joint centre of rotation defined using a closed-form solution for absolute orientation. Paired t tests were performed to determine if the centre of rotation of the elbow differed significantly (P<0·05) pre- and postoperatively and between left and right limbs. RESULTS: There was no significant difference in three-dimensional orientation of the elbow axis between pre and postoperative measurements or between left and right limbs. CLINICAL SIGNIFICANCE: A critical factor in obtaining a successful functional outcome following elbow arthroplasty in humans is accurate reconstruction of the anatomic centre of rotation. The first generation TATE canine elbow arthroplasty cartridge and its instrumentation accurately reconstructed the anatomic centre of rotation in 8 of the 10 elbows assessed in this ex vivo model.

An overview of the biology and status of undulate ray Raja undulata in the north-east Atlantic Ocean.

The undulate ray Raja undulata is one of the lesser-known skates occurring on the continental shelf of the north-east Atlantic Ocean. It is patchily distributed throughout its range, with sites of local abundance in the central English Channel and off the coasts of Ireland, France, Spain and Portugal. Raja undulata is most abundant in coastal waters (<50 m deep) and is often found in proximity to large estuaries, rias and bays. It is a relatively large-bodied species, attaining a maximum total length (L(T) ) of at least 114 cm, with females maturing at an L(T) of c. 84 cm in Portuguese waters. Although infrequently taken in existing trawl surveys, it can be locally abundant in certain areas, where it can be the dominant skate species. Given its large size, patchy distribution and concern over the possibilities of localized depletions, the IUCN listed R. undulata as an endangered species and, since 2009, the European Union has established regulations to prohibit commercial fisheries landing the species. Given the increased interest in the species, a synopsis of current knowledge is provided, and available data from internationally co-ordinated trawl surveys presented.

Species composition of skates (Rajidae) in commercial fisheries around the British Isles and their discarding patterns.

Recent regulations have required European nations to report commercial landings of Rajidae (skates) to species level since 2008. Morphological similarities between some species, variability in colouration and regional differences in common names may compromise the accuracy of some of these data. An increased proportion of rajid landings reported by the U.K. (England, Wales and Northern Ireland) are now reported to species level (42% in 2008, rising to 92% in 2010). Recent landings (2007-2010) of Rajidae by the U.K. indicated that the majority of reported landings were made by otter trawl (55·9%), tangle and gillnet (18·7%) and beam trawl (15·5%). Approximately 70% of recent landings originated from four ICES Divisions: the Irish Sea (VIIa), western English Channel (VIIe), Bristol Channel (VIIf) and southern North Sea (IVc). Recent species-specific landings of Rajidae are appraised in terms of the species reported and the overall composition, and potential problems identified. Data from observer trips have been used to estimate the species composition of Rajidae taken in some of the main commercial fisheries operating around the British Isles, and these data are compared to landings. Although there was typically broad agreement between these data sets in terms of the main species landed, misidentification issues were apparent and Rajidae with highly patchy distributions may be under-represented in observer data. Data from observer trips were also used to examine the discard and retention pattern. Most rajid species were first retained from total lengths, L(T) , of 27-34 cm, with 50% retention occurring at between 49 and 51 cm and near-full retention at L(T) of 60-67 cm. Beam trawls captured a higher proportion of smaller individuals, whilst gillnets (>150 mm mesh size) caught proportionally more larger rajids.

The relationship between nicotinic receptors and cognitive functioning in healthy aging: An in vivo positron emission tomography (PET) study with 2-[(18)F]fluoro-A-85380.

Extensive experimental and neuropathological evidence supports the general hypothesis that decline in the basal forebrain cholinergic system contributes significantly to age-related cognitive impairment. Postmortem studies suggest reductions in neuronal nicotinic acetylcholine receptors (nAChRs, particularly the alpha(4)beta(2) subtype) with aging. This study aimed to determine the distribution of alpha(4)beta(2)-subtype nAChRs in vivo by 2-FA PET in healthy subjects (aged 21-83) and to establish whether there is an age-related decline in nAChRs. Furthermore, the relationship between PET measures of 2-FA binding and neurobehavioral measures of cognitive function was investigated. All participants were nonsmokers and underwent extensive cognitive testing and a PET scan after injection of 2-FA (200 MBq). Brain regional 2-FA binding was assessed through a simplified estimation of distribution volume (DV(S)). As expected, increasing age was associated with poorer cognitive performance, particularly on tasks assessing episodic memory and attentional processes. No significant age-related differences in regional nAChR DV(S) were found. Furthermore, no significant correlations were found between cognitive measures and nAChR DV(S). These results are consistent with recent studies suggesting the stability of cholinergic markers during senescence. It is plausible that changes in alpha(4)beta(2) nAChRs do occur with advancing age, but are beyond detection by the clinical 2-FA PET approach adopted here. However, this approach may be appropriate for use in pathologies considered to undergo extensive nAChR loss such as Alzheimer's disease and Parkinson's disease.

Galantamine-induced improvements in cognitive function are not related to alterations in alpha(4)beta (2) nicotinic receptors in early Alzheimer's disease as measured in vivo by 2-[18F]fluoro-A-85380 PET.

INTRODUCTION: The nicotinic acetylcholine receptor (nAChR) system plays a regulatory role in a number of cognitive processes. Cholinesterase inhibitors (i.e., galantamine) that potentiate cholinergic neurotransmission improve cognitive function in Alzheimer's disease (AD); however, the relationship between these effects and associated changes in nAChRs are yet to be established in vivo. MATERIALS AND METHODS: 2-[18F]Fluoro-A-85380 (2-FA) binds to nAChRs and with positron emission tomography (PET) imaging provides a composite measure of receptor density and ligand affinity. This study aimed to: (1) quantify nAChRs in vivo in 15 drug-naïve patients with mild AD before and after chronic treatment with galantamine, using 2-FA and PET, and (2) examine the relationship between treatment-induced changes in nAChRs and improvements in cognitive function. Participants were nonsmokers and underwent extensive cognitive testing and a PET scan after injection of approximately 200 MBq of 2-FA on two occasions (before and after 12 weeks, galantamine treatment). A 3-day washout period preceded the second scan. Brain regional 2-FA binding was assessed through a simplified estimation of distribution volume (DV(S)). RESULTS: Performance on global measures of cognition significantly improved following galantamine treatment (p < 0.05). This improvement extended to specific cognitive measures of language and verbal learning. No significant differences in nAChR DV(S) before and after galantamine treatment were found. The treatment-induced improvement in cognition was not correlated with regional or global nAChR DV(S), suggesting that changes in nAChRs may not be responsible for the improvements in cognition following galantamine in patients with mild AD.