Neuroimaging and Analytical Methods for Studying the Pathways from Mild Cognitive Impairment to Alzheimer’s Disease: Protocol for a Rapid Systematic Review

Background Alzheimer’s disease (AD) is a neurodegenerative disorder commonly associated with deficits of cognition and changes in behavior. Mild cognitive impairment (MCI) is the prodromal stage of AD that is defined by slight cognitive decline. Not all with MCI progress to AD dementia. Thus, the accurate prediction of progression to Alzheimer’s, particularly in the stage of MCI could potentially offer developing treatments to delay or prevent the transition process. The objective of the present study is to investigate the most recent neuroimaging procedures in the domain of prediction of transition from MCI to AD dementia for clinical applications and to systematically discuss the machine learning techniques used for the prediction of MCI conversion. Methods Electronic databases including PubMed, SCOPUS, and Web of Science will be searched from January 1, 2017, to the date of search commencement to provide a rapid review of the most recent studies that have investigated the prediction of conversion from MCI to Alzheimer’s using neuroimaging modalities in randomized trial or observational studies. Two reviewers will screen full texts of included papers using predefined eligibility criteria. Studies will be included if addressed research on AD dementia and MCI, explained the results in a way that would be able to report the performance measures such as the accuracy, sensitivity, and specificity. Only studies addressed Alzheimer’s type of dementia and its early-stage MCI using neuroimaging modalities will be included. We will exclude other forms of dementia such as vascular dementia, frontotemporal dementia, and Parkinson’s disease. The risk of bias in individual studies will be appraised using an appropriate tool. If feasible, we will conduct a random effects meta-analysis. Sensitivity analyses will be conducted to explore the potential sources of heterogeneity. Discussion The information gathered in our study will establish the extent of the evidence underlying the prediction of conversion to AD dementia from its early stage and will provide a rigorous and updated synthesis of neuroimaging modalities allied with the data analysis techniques used to measure the brain changes during the conversion process

Moderate-Intensity Physical Activity, Music and Art Activities Preserved Cognitive Health in Older Adults: An Argument for Social Prescribing Solution

Introduction: Rates of dementia are projected to increase over the coming years as global populations age. Without a treatment to slow the progression of dementia, many health policies are focusing on preventing dementia by slowing the rate of cognitive decline with age. However, it is unclear which lifestyle changes in old age meaningfully reduce the rate of cognitive decline associated with aging. Objectives: Use existing, multi-year longitudinal health data to determine if engagement in a variety of different lifestyle activities can slow the rate of cognitive decline as older adults age. Method: Data from the English Longitudinal Study of Aging was analyzed using a quasi-experimental, efficient matched-pair design inspired by the clinical trial methodology. Changes in short-term memory scores were assessed over a multi-year interval for groups who undertook one of 11 different lifestyle activities, compared to control groups matched across confounding socioeconomic and lifestyle factors. Results: Two factors, moderate-intensity physical activity and learning activities, resulted in significant positive impact on cognitive function. Conclusion: Our analysis brings cognitive benefit arguments in favor of two lifestyle activities, moderate-intensity physical activity and learning activities, while rejecting other factors advanced by the literature such as vigorous-intensity physical activity. Those findings justify and encourage the development of new lifestyle health programs by health authorities and bring forward the new health system solution, social prescribing

Electrophysiological indices of feedback processing

xii, 76 leaves : ill. (chiefly col.) ; 29 cmAll sentient organisms use contextual information to assess the amount of reward associated with a particular behavior. Human beings have arguably evolved the most sophisticated of these mechanisms and are capable of integrating information over a long duration of time to accurately assess the expected outcome of a chosen action. This thesis used electroencephalography (EEG) to measure how the human brain processes rewarding and punishing feedback in a gambling-type game with variable risk and reward. Experiment 1 determined that phase-locked (evoked) and non-phase-locked (induced) electroencephalographic activity share only partially overlapping generators in human mediofrontal cortex. Experiment 2 determined that the magnitude of certain evoked EEG components during reward processing tracked subsequent changes in bets placed in the next round. These results extend the body of literature by assessing the overlap between induced and evoked EEG components and the role of evoked activity in affecting future decision making

Effects of dalcetrapib in patients with a recent acute coronary syndrome

In observational analyses, higher levels of high-density lipoprotein (HDL) cholesterol have been associated with a lower risk of coronary heart disease events. However, whether raising HDL cholesterol levels therapeutically reduces cardiovascular risk remains uncertain. Inhibition of cholesteryl ester transfer protein (CETP) raises HDL cholesterol levels and might therefore improve cardiovascular outcomes

phot1 inhibition of ABCB19 primes lateral auxin fluxes in the shoot apex required for phototropism

It is well accepted that lateral redistribution of the phytohormone auxin underlies the bending of plant organs towards light. In monocots, photoreception occurs at the shoot tip above the region of differential growth. Despite more than a century of research, it is still unresolved how light regulates auxin distribution and where this occurs in dicots. Here, we establish a system in Arabidopsis thaliana to study hypocotyl phototropism in the absence of developmental events associated with seedling photomorphogenesis. We show that auxin redistribution to the epidermal sites of action occurs at and above the hypocotyl apex, not at the elongation zone. Within this region, we identify the auxin efflux transporter ATP-BINDING CASSETTE B19 (ABCB19) as a substrate target for the photoreceptor kinase PHOTOTROPIN 1 (phot1). Heterologous expression and physiological analyses indicate that phosphorylation of ABCB19 by phot1 inhibits its efflux activity, thereby increasing auxin levels in and above the hypocotyl apex to halt vertical growth and prime lateral fluxes that are subsequently channeled to the elongation zone by PIN-FORMED 3 (PIN3). Together, these results provide new insights into the roles of ABCB19 and PIN3 in establishing phototropic curvatures and demonstrate that the proximity of light perception and differential phototropic growth is conserved in angiosperm

Cenozoic Global Sea Level, Sequences, and the New Jersey Transect: Results from Coastal Plain and Continental Slope Drilling

The New Jersey Sea Level Transect was designed to evaluate the relationships among global sea level (eustatic) change, unconformity-bounded sequences, and variations in subsidence, sediment supply, and climate on a passive continental margin. By sampling and dating Cenozoic strata from coastal plain and continental slope locations, we show that sequence boundaries correlate (within ±0.5 myr) regionally (onshore-offshore) and interregionally (New Jersey-Alabama-Bahamas), implicating a global cause. Sequence boundaries correlate with δ18O increases for at least the past 42 myr, consistent with an ice volume (glacioeustatic) control, although a causal relationship is not required because of uncertainties in ages and correlations. Evidence for a causal connection is provided by preliminary Miocene data from slope Site 904 that directly link δ18O increases with sequence boundaries. We conclude that variation in the size of ice sheets has been a primary control on the formation of sequence boundaries since ∼42 Ma. We speculate that prior to this, the growth and decay of small ice sheets caused small-amplitude sea level changes (less than 20 m) in this supposedly ice-free world because Eocene sequence boundaries also appear to correlate with minor δ18O increases. Subsidence estimates (backstripping) indicate amplitudes of short-term (million-year scale) lowerings that are consistent with estimates derived from δ18O studies (25–50 m in the Oligocene-middle Miocene and 10–20 m in the Eocene) and a long-term lowering of 150–200 m over the past 65 myr, consistent with estimates derived from volume changes on mid-ocean ridges. Although our results are consistent with the general number and timing of Paleocene to middle Miocene sequences published by workers at Exxon Production Research Company, our estimates of sea level amplitudes are substantially lower than theirs. Lithofacies patterns within sequences follow repetitive, predictable patterns: (1) coastal plain sequences consist of basal transgressive sands overlain by regressive highstand silts and quartz sands; and (2) although slope lithofacies variations are subdued, reworked sediments constitute lowstand deposits, causing the strongest, most extensive seismic reflections. Despite a primary eustatic control on sequence boundaries, New Jersey sequences were also influenced by changes in tectonics, sediment supply, and climate. During the early to middle Eocene, low siliciclastic and high pelagic input associated with warm climates resulted in widespread carbonate deposition and thin sequences. Late middle Eocene and earliest Oligocene cooling events curtailed carbonate deposition in the coastal plain and slope, respectively, resulting in a switch to siliciclastic sedimentation. In onshore areas, Oligocene sequences are thin owing to low siliciclastic and pelagic input, and their distribution is patchy, reflecting migration or progradation of depocenters; in contrast, Miocene onshore sequences are thicker, reflecting increased sediment supply, and they are more complete downdip owing to simple tectonics. We conclude that the New Jersey margin provides a natural laboratory for unraveling complex interactions of eustasy, tectonics, changes in sediment supply, and climate change

Divergent roles of IL-23 and IL-12 in host defense against Klebsiella pneumoniae

Interleukin (IL)-23 is a heterodimeric cytokine that shares the identical p40 subunit as IL-12 but exhibits a unique p19 subunit similar to IL-12 p35. IL-12/23 p40, interferon γ (IFN-γ), and IL-17 are critical for host defense against Klebsiella pneumoniae. In vitro, K. pneumoniae–pulsed dendritic cell culture supernatants elicit T cell IL-17 production in a IL-23–dependent manner. However, the importance of IL-23 during in vivo pulmonary challenge is unknown. We show that IL-12/23 p40–deficient mice are exquisitely sensitive to intrapulmonary K. pneumoniae inoculation and that IL-23 p19−/−, IL-17R−/−, and IL-12 p35−/− mice also show increased susceptibility to infection. p40−/− mice fail to generate pulmonary IFN-γ, IL-17, or IL-17F responses to infection, whereas p35−/− mice show normal IL-17 and IL-17F induction but reduced IFN-γ. Lung IL-17 and IL-17F production in p19−/− mice was dramatically reduced, and this strain showed substantial mortality from a sublethal dose of bacteria (103 CFU), despite normal IFN-γ induction. Administration of IL-17 restored bacterial control in p19−/− mice and to a lesser degree in p40−/− mice, suggesting an additional host defense requirement for IFN-γ in this strain. Together, these data demonstrate independent requirements for IL-12 and IL-23 in pulmonary host defense against K. pneumoniae, the former of which is required for IFN-γ expression and the latter of which is required for IL-17 production

The Phanerozoic Record of Global Sea-Level Change

We review Phanerozoic sea-level changes [543 million years ago (Ma) to the present] on various time scales and present a new sea-level record for the past 100 million years (My). Long-term sea level peaked at 100 ± 50 meters during the Cretaceous, implying that ocean-crust production rates were much lower than previously inferred. Sea level mirrors oxygen isotope variations, reflecting ice-volume change on the 104- to 106-year scale, but a link between oxygen isotope and sea level on the 107-year scale must be due to temperature changes that we attribute to tectonically controlled carbon dioxide variations. Sea-level change has influenced phytoplankton evolution, ocean chemistry, and the loci of carbonate, organic carbon, and siliciclastic sediment burial. Over the past 100 My, sea-level changes reflect global climate evolution from a time of ephemeral Antarctic ice sheets (100 to 33 Ma), through a time of large ice sheets primarily in Antarctica (33 to 2.5 Ma), to a world with large Antarctic and large, variable Northern Hemisphere ice sheets (2.5 Ma to the present)

A Detailed Observational Analysis of V1324 Sco, the Most Gamma-Ray Luminous Classical Nova to Date

It has recently been discovered that some, if not all, classical novae emit GeV gamma rays during outburst, but the mechanisms involved in the production of the gamma rays are still not well understood. We present here a comprehensive multi-wavelength dataset---from radio to X-rays---for the most gamma-ray luminous classical nova to-date, V1324 Sco. Using this dataset, we show that V1324 Sco is a canonical dusty Fe-II type nova, with a maximum ejecta velocity of 2600 km s$^{-1}$ and an ejecta mass of few $\times 10^{-5}$ M$_{\odot}$. There is also evidence for complex shock interactions, including a double-peaked radio light curve which shows high brightness temperatures at early times. To explore why V1324~Sco was so gamma-ray luminous, we present a model of the nova ejecta featuring strong internal shocks, and find that higher gamma-ray luminosities result from higher ejecta velocities and/or mass-loss rates. Comparison of V1324~Sco with other gamma-ray detected novae does not show clear signatures of either, and we conclude that a larger sample of similarly well-observed novae is needed to understand the origin and variation of gamma rays in novae.Comment: 26 pages, 13 figure