A graph-based integration of multimodal brain imaging data for the detection of early mild cognitive impairment (E-MCI)

Alzheimer's disease (AD) is the most common cause of dementia in older adults. By the time an individual has been diagnosed with AD, it may be too late for potential disease modifying therapy to strongly influence outcome. Therefore, it is critical to develop better diagnostic tools that can recognize AD at early symptomatic and especially pre-symptomatic stages. Mild cognitive impairment (MCI), introduced to describe a prodromal stage of AD, is presently classified into early and late stages (E-MCI, L-MCI) based on severity. Using a graph-based semi-supervised learning (SSL) method to integrate multimodal brain imaging data and select valid imaging-based predictors for optimizing prediction accuracy, we developed a model to differentiate E-MCI from healthy controls (HC) for early detection of AD. Multimodal brain imaging scans (MRI and PET) of 174 E-MCI and 98 HC participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort were used in this analysis. Mean targeted region-of-interest (ROI) values extracted from structural MRI (voxel-based morphometry (VBM) and FreeSurfer V5) and PET (FDG and Florbetapir) scans were used as features. Our results show that the graph-based SSL classifiers outperformed support vector machines for this task and the best performance was obtained with 66.8% cross-validated AUC (area under the ROC curve) when FDG and FreeSurfer datasets were integrated. Valid imaging-based phenotypes selected from our approach included ROI values extracted from temporal lobe, hippocampus, and amygdala. Employing a graph-based SSL approach with multimodal brain imaging data appears to have substantial potential for detecting E-MCI for early detection of prodromal AD warranting further investigation

Memory enhancing drugs and Alzheimer’s Disease: Enhancing the self or preventing the loss of it?

In this paper we analyse some ethical and philosophical questions related to the development of memory enhancing drugs (MEDs) and anti-dementia drugs. The world of memory enhancement is coloured by utopian thinking and by the desire for quicker, sharper, and more reliable memories. Dementia is characterized by decline, fragility, vulnerability, a loss of the most important cognitive functions and even a loss of self. While MEDs are being developed for self-improvement, in Alzheimer’s Disease (AD) the self is being lost. Despite this it is precisely those patients with AD and other forms of dementia that provide the subjects for scientific research on memory improvement. Biomedical research in the field of MEDs and anti-dementia drugs appears to provide a strong impetus for rethinking what we mean by ‘memory’, ‘enhancement’, ‘therapy’, and ‘self’. We conclude (1) that the enhancement of memory is still in its infancy, (2) that current MEDs and anti-dementia drugs are at best partially and minimally effective under specific conditions, (3) that ‘memory᾿and ‘enhancement᾿are ambiguous terms, (4) that there is no clear-cut distinction between enhancement and therapy, and (5) that the research into MEDs and anti-dementia drugs encourages a reductionistic view of the human mind and of the self

Restricted and Repetitive Behavior and Brain Functional Connectivity in Infants at Risk for Developing Autism Spectrum Disorder

Background: Restricted and repetitive behaviors (RRBs), detectable by 12 months in many infants in whom autism spectrum disorder (ASD) is later diagnosed, may represent some of the earliest behavioral markers of ASD. However, brain function underlying the emergence of these key behaviors remains unknown. Methods: Behavioral and resting-state functional connectivity (fc) magnetic resonance imaging data were collected from 167 children at high and low familial risk for ASD at 12 and 24 months (n = 38 at both time points). Twenty infants met criteria for ASD at 24 months. We divided RRBs into four subcategories (restricted, stereotyped, ritualistic/sameness, self-injurious) and used a data-driven approach to identify functional brain networks associated with the development of each RRB subcategory. Results: Higher scores for ritualistic/sameness behavior were associated with less positive fc between visual and control networks at 12 and 24 months. Ritualistic/sameness and stereotyped behaviors were associated with less positive fc between visual and default mode networks at 12 months. At 24 months, stereotyped and restricted behaviors were associated with more positive fc between default mode and control networks. Additionally, at 24 months, stereotyped behavior was associated with more positive fc between dorsal attention and subcortical networks, whereas restricted behavior was associated with more positive fc between default mode and dorsal attention networks. No significant network-level associations were observed for self-injurious behavior. Conclusions: These observations mark the earliest known description of functional brain systems underlying RRBs, reinforce the construct validity of RRB subcategories in infants, and implicate specific neural substrates for future interventions targeting RRBs

Parasite Zoonoses and Wildlife: Emerging Issues

The role of wildlife as important sources, reservoirs and amplifiers of emerging human and domestic livestock pathogens, in addition to well recognized zoonoses of public health significance, has gained considerable attention in recent years. However, there has been little attention given to the transmission and impacts of pathogens of human origin, particularly protozoan, helminth and arthropod parasites, on wildlife. Substantial advances in molecular technologies are greatly improving our ability to follow parasite flow among host species and populations and revealing valuable insights about the interactions between cycles of transmission. Here we present several case studies of parasite emergence, or risk of emergence, in wildlife, as a result of contact with humans or anthropogenic activities. For some of these parasites, there is growing evidence of the serious consequences of infection on wildlife survival, whereas for others, there is a paucity of information about their impact

Horizontal Branch Stars: The Interplay between Observations and Theory, and Insights into the Formation of the Galaxy

We review HB stars in a broad astrophysical context, including both variable and non-variable stars. A reassessment of the Oosterhoff dichotomy is presented, which provides unprecedented detail regarding its origin and systematics. We show that the Oosterhoff dichotomy and the distribution of globular clusters (GCs) in the HB morphology-metallicity plane both exclude, with high statistical significance, the possibility that the Galactic halo may have formed from the accretion of dwarf galaxies resembling present-day Milky Way satellites such as Fornax, Sagittarius, and the LMC. A rediscussion of the second-parameter problem is presented. A technique is proposed to estimate the HB types of extragalactic GCs on the basis of integrated far-UV photometry. The relationship between the absolute V magnitude of the HB at the RR Lyrae level and metallicity, as obtained on the basis of trigonometric parallax measurements for the star RR Lyrae, is also revisited, giving a distance modulus to the LMC of (m-M)_0 = 18.44+/-0.11. RR Lyrae period change rates are studied. Finally, the conductive opacities used in evolutionary calculations of low-mass stars are investigated. [ABRIDGED]Comment: 56 pages, 22 figures. Invited review, to appear in Astrophysics and Space Scienc

Search for Neutral Higgs Bosons of the Minimal Supersymmetric Standard Model in e+e- Interactions at \sqrt{s} = 189 GeV

A search for the lightest neutral scalar and neutral pseudoscalar Higgs bosons in the Minimal Supersymmetric Standard Model is performed using 176.4 pb^-1 of integrated luminosity collected by L3 at a center-of-mass energy of 189 GeV. No signal is observed, and the data are consistent with the expected Standard Model background. Lower limits on the masses of the lightest neutral scalar and pseudoscalar Higgs bosons are given as a function of tan(beta). Lower mass limits for tan(beta)>1 are set at the 95% confidence level to be m_h > 77.1 GeV and m_A > 77.1 GeV

Search for Extra Dimensions in Boson and Fermion Pair Production in e+e- Interactions at LEP

Extra spatial dimensions are proposed by recent theories that postulate the scale of gravity to be of the same order as the electroweak scale. A sizeable interaction between gravitons and Standard Model particles is then predicted. Effects of these new interactions in boson and fermion pair production are searched for in the data sample collected at centre-of-mass energies above the Z pole by the L3 detector at LEP. In addition, the direct production of a graviton associated with a Z boson is investigated. No statistically significant hints for the existence of these effects are found and lower limits in excess of 1 TeV are derived on the scale of this new theory of gravity

Measurement of the Probability of Gluon Splitting into Charmed Quarks in Hadronic Z Decays

We have measured the probability, n(g->cc~), of a gluon splitting into a charm-quark pair using 1.7 million hadronic Z decays collected by the L3 detector. Two independent methods have been applied to events with a three-jet topology. One method relies on tagging charmed hadrons by identifying a lepton in the lowest energy jet. The other method uses a neural network based on global event shape parameters. Combining both methods, we measure n(g->cc~)= [2.45 +/- 0.29 +/- 0.53]%

Measurement of Hadron and Lepton-Pair Production at 130GeV < \sqrt{s} < 189 GeV at LEP

We report on measurements of e+e- annihilation into hadrons and lepton pairs. The data have been collected with the L3 detector at LEP at centre-of-mass energies between 130 and 189 GeV. Using a total integrated luminosity of 243.7 pb^-1, 25864 hadronic and 8573 lepton-pair events are selected for the measurement of cross sections and leptonic forward-backward asymmetries. The results are in good agreement with Standard Model predictions

Measurement of Triple-Gauge-Boson Couplings of the W Boson at LEP

We report on measurements of the triple-gauge-boson couplings of the W boson in e+e- collisions with the L3 detector at LEP. W-pair, single-W and single-photon events are analysed in a data sample corresponding to a total luminosity of 76.7 pb^{-1} collected at centre-of-mass energies between 161 GeV and 183 GeV. CP-conserving as well as both C- and P-conserving triple-gauge-boson couplings are determined. The results, in good agreement with the Standard-Model expectations, confirm the existence of the self coupling among the electroweak gauge bosons and constrain its structure