AimsHyperphosphorylated tau neuronal cytoplasmic inclusions (ht‐NCI) are the best protein correlate of clinical decline in Alzheimer's disease (AD). Qualitative evidence identifies ht‐NCI ...accumulating in the isodendritic core before the entorhinal cortex. Here, we used unbiased stereology to quantify ht‐NCI burden in the locus coeruleus (LC) and dorsal raphe nucleus (DRN), aiming to characterize the impact of AD pathology in these nuclei with a focus on early stages.MethodsWe utilized unbiased stereology in a sample of 48 well‐characterized subjects enriched for controls and early AD stages. ht‐NCI counts were estimated in 60‐μm‐thick sections immunostained for p‐tau throughout LC and DRN. Data were integrated with unbiased estimates of LC and DRN neuronal population for a subset of cases.ResultsIn Braak stage 0, 7.9% and 2.6% of neurons in LC and DRN, respectively, harbour ht‐NCIs. Although the number of ht‐NCI+ neurons significantly increased by about 1.9× between Braak stages 0 to I in LC (P = 0.02), we failed to detect any significant difference between Braak stage I and II. Also, the number of ht‐NCI+ neurons remained stable in DRN between all stages 0 and II. Finally, the differential susceptibility to tau inclusions among nuclear subdivisions was more notable in LC than in DRN.ConclusionsLC and DRN neurons exhibited ht‐NCI during AD precortical stages. The ht‐NCI increases along AD progression on both nuclei, but quantitative changes in LC precede DRN changes.
Stereological analysis of tau pathology in the locus coeruleus and dorsal raphe nucleus in early Alzheimer's disease demonstrate that early involvement of brain stem nuclei has important functional implications.
We report the INTernational Gamma-ray Astrophysics Laboratory (INTEGRAL) detection of the short gamma-ray burst GRB 170817A (discovered by Fermi-GBM) with a signal-to-noise ratio of 4.6, and, for the ...first time, its association with the gravitational waves (GWs) from binary neutron star (BNS) merging event GW170817 detected by the LIGO and Virgo observatories. The significance of association between the gamma-ray burst observed by INTEGRAL and GW170817 is 3.2 , while the association between the Fermi-GBM and INTEGRAL detections is 4.2 . GRB 170817A was detected by the SPI-ACS instrument about 2 s after the end of the GW event. We measure a fluence of (1.4 0.4 0.6) × 10−7 erg cm−2 (75-2000 keV), where, respectively, the statistical error is given at the 1 confidence level, and the systematic error corresponds to the uncertainty in the spectral model and instrument response. We also report on the pointed follow-up observations carried out by INTEGRAL, starting 19.5 hr after the event, and lasting for 5.4 days. We provide a stringent upper limit on any electromagnetic signal in a very broad energy range, from 3 keV to 8 MeV, constraining the soft gamma-ray afterglow flux to <7.1 × 10−11 erg cm−2 s−1 (80-300 keV). Exploiting the unique capabilities of INTEGRAL, we constrained the gamma-ray line emission from radioactive decays that are expected to be the principal source of the energy behind a kilonova event following a BNS coalescence. Finally, we put a stringent upper limit on any delayed bursting activity, for example, from a newly formed magnetar.
Gamma-ray lines from radioactive decay of unstable isotopes produced in massive- star and supernova nucleosynthesis have been measured with INTEGRAL over the past ten years, complementing the earlier ...COMPTEL survey. 26Al has become a tool to study specific source regions, such as massive-star groups and associations in nearby regions which can be discriminated from the galactic-plane background, and the inner Galaxy where Doppler shifted lines add to the astronomical information. Recent findings are that superbubbles show a remarkable asymmetry, on average, in the spiral arms of our galaxy. 60Fe is co-produced by the sources of 26Al, and the isotopic ratio from their nucleosynthesis encodes stellar-structure information. Annihilation gamma-rays from positrons in interstellar space show a puzzling bright and extended source region central to our Galaxy, but also may be partly related to nucleosynthesis. 56Ni and 44Ti isotope gamma-rays have been used to constrain supernova explosion mechanisms. Here we summarize latest results using the accumulated multi-year database of observations, and discuss their astrophysical interpretations. We also add a comparison of isotopic ratios between the ISM of the current Galaxy and the solar vicinity at solar-system formation time.
There is mounting anecdotal and empirical evidence that gardening and art-making afford therapeutic benefits. This randomly controlled pilot study tested the hypothesis that participation in ...group-based indoor gardening or art-making activities for one hour twice a week for four weeks would provide quantifiably different therapeutic benefits to a population of healthy women ages 26-49. A population of 42 volunteers was randomly assigned to parallel gardening or art-making treatment groups. A total of 36 participants initiated the treatment protocol and 32 (Gardening n = 15 and Art n = 17) received the interventions and completed all assessments. Treatments included eight one-hour group-based gardening or art intervention sessions. Self-report psychometric assessments were conducted for anxiety, depression symptomatology, mood disturbance, stress, satisfaction with discretionary social activities, and quality of life measures. Cardiac physiological data were also collected. Outcomes were measured at baseline, during, and post-intervention. Engaging in both gardening and art-making activities resulted in apparent therapeutic improvements for self-reported total mood disturbance, depression symptomatology, and perceived stress with different effect sizes following eight one-hour treatment sessions. Gardening also resulted in improvements for indications of trait anxiety. Based on time-course evidence, dosage responses were observed for total mood disturbance, perceived stress, and depression symptomatology for both gardening and art-making. However, gardening or art-making did not have an apparent influence on heart rate or blood pressure or result in marked improvement for satisfaction with discretionary leisure activities. The data did not support the hypothesis of differential therapeutic benefits of gardening and art-making for healthy women. When taken together, group-based gardening or art-making can provide quantitatively measurable improvements in healthy women's psychosocial health status that imply potentially important public health benefits.
Originating from relativistic quantum field theory, Dirac fermions have been invoked recently to explain various peculiar phenomena in condensed-matter physics, including the novel quantum Hall ...effect in graphene, the magnetic-field-driven metal-insulator-like transition in graphite, superfluidity in 3He (ref. 5) and the exotic pseudogap phase of high-temperature superconductors. Despite their proposed key role in those systems, direct experimental evidence of Dirac fermions has been limited. Here, we report the first direct observation of relativistic Dirac fermions with linear dispersion near the Brillouin zone (BZ) corner H, which coexist with quasiparticles that have a parabolic dispersion near another BZ corner K. In addition, we also report a large electron pocket that we attribute to defect-induced localized states. Thus, graphite presents a system in which massless Dirac fermions, quasiparticles with finite effective mass and defect states all contribute to the low-energy electronic dynamics.
CONTEXT Air pollution is a risk factor for cardiovascular diseases (CVD), but the underlying biological mechanisms are not well understood. OBJECTIVE To determine whether markers related to CVD ...pathophysiological pathways (biomarkers for systemic inflammation and thrombosis, heart rate, and blood pressure) are sensitive to changes in air pollution. DESIGN, SETTING, AND PARTICIPANTS Using a quasi-experimental opportunity offered by greatly restricted air pollution emissions during the Beijing Olympics, we measured pollutants daily and the outcomes listed below in 125 healthy young adults before, during, and after the 2008 Olympics (June 2-October 30). We used linear mixed-effects models to estimate the improvement in outcome levels during the Olympics and the anticipated reversal of outcome levels after pollution controls ended to determine whether changes in outcome levels were associated with changes in pollutant concentrations. MAIN OUTCOME MEASURES C-reactive protein (CRP), fibrinogen, von Willebrand factor, soluble CD40 ligand (sCD40L), soluble P-selectin (sCD62P) concentrations; white blood cell count (WBC); heart rate; and blood pressure. RESULTS Concentrations of particulate and gaseous pollutants decreased substantially (−13% to −60%) from the pre-Olympic period to the during-Olympic period. Using 2-sided tests conducted at the .003 level, we observed statistically significant improvements in sCD62P levels by −34.0% (95% CI, −38.4% to −29.2%; P < .001) from a pre-Olympic mean of 6.29 ng/mL to a during-Olympic mean of 4.16 ng/mL and von Willebrand factor by −13.1% (95% CI, −18.6% to −7.5%; P < .001) from 106.4% to 92.6%. After adjustments for multiple comparisons, changes in the other outcomes were not statistically significant. In the post-Olympic period when pollutant concentrations increased, most outcomes approximated pre-Olympic levels, but only sCD62P and systolic blood pressure were significantly worsened from the during-Olympic period. The fraction of above-detection-limit values for CRP (percentage ≥ 0.3 mg/L) was reduced from 55% in the pre-Olympic period to 46% in the during-Olympic period and reduced further to 36% in the post-Olympic period. Interquartile range increases in pollutant concentrations were consistently associated with statistically significant increases in fibrinogen, von Willebrand factor, heart rate, sCD62P, and sCD40L concentrations. CONCLUSIONS Changes in air pollution levels during the Beijing Olympics were associated with acute changes in biomarkers of inflammation and thrombosis and measures of cardiovascular physiology in healthy young persons. These findings are of uncertain clinical significance.
Unprecedented pollution control actions during the Beijing Olympics provided a quasi-experimental opportunity to examine biologic responses to drastic changes in air pollution levels.
To determine ...whether changes in levels of biomarkers reflecting pulmonary inflammation and pulmonary and systemic oxidative stress were associated with changes in air pollution levels in healthy young adults.
We measured fractional exhaled nitric oxide, a number of exhaled breath condensate markers (H(+), nitrite, nitrate, and 8-isoprostane), and urinary 8-hydroxy-2-deoxyguanosine in 125 participants twice in each of the pre- (high pollution), during- (low pollution), and post-Olympic (high pollution) periods. We measured concentrations of air pollutants near where the participants lived and worked. We used mixed-effects models to estimate changes in biomarker levels across the three periods and to examine whether changes in biomarker levels were associated with changes in pollutant concentrations, adjusting for meteorologic parameters.
From the pre- to the during-Olympic period, we observed significant and often large decreases (ranging from -4.5% to -72.5%) in levels of all the biomarkers. From the during-Olympic to the post-Olympic period, we observed significant and larger increases (48-360%) in levels of these same biomarkers. Moreover, increased pollutant concentrations were consistently associated with statistically significant increases in biomarker levels.
These findings support the important role of oxidative stress and that of pulmonary inflammation in mediating air pollution health effects. The findings demonstrate the utility of novel and noninvasive biomarkers in the general population consisting largely of healthy individuals.
Abstract
Type Ia supernovae (SNe Ia) may originate from a wide variety of explosion scenarios and progenitor channels. They exhibit a factor of ≈10 difference in brightness and thus a differentiation ...in the mass of
56
Ni →
56
Co →
56
Fe. We present a study on the fate of positrons within SNe Ia in order to evaluate their escape fractions and energy spectra. Our detailed Monte Carlo transport simulations for positrons and
γ
-rays include both
β
+
decay of
56
Co and pair production. We simulate a wide variety of explosion scenarios, including the explosion of white dwarfs (WDs) close to the Chandrasekhar mass (
M
Ch
), He-triggered explosions of sub-
M
Ch
WDs, and dynamical mergers of two WDs. For each model, we study the influence of the size and morphology of the progenitor magnetic field between 1 and 10
13
G. Population synthesis based on the observed brightness distribution of SNe Ia was used to estimate the overall contributions to Galactic positrons due to escape from SNe Ia. We find that this is dominated by SNe Ia of normal brightness, where variations in the distribution of emitted positrons are small. We estimate a total SNe Ia contribution to Galactic positrons of <2% and, depending on the magnetic field morphology, <6–20% for
M
Ch
and sub-
M
Ch
, respectively.
Persistent pain may follow nerve injuries associated with invasive therapeutic interventions. About 3% to 7% of the patients remain with chronic pain after endodontic treatment, and these are ...described as suffering from painful posttraumatic trigeminal neuropathy (PTTN). Unfortunately, we are unable to identify which patients undergoing such procedures are at increased risk of developing PTTN. Recent findings suggest that impaired endogenous analgesia may be associated with the development of postsurgical chronic pain. We hypothesized that patients with PTTN display pronociceptive pain modulation, in line with other chronic pain disorders. Dynamic (conditioned pain modulation, temporal summation) and static (response to mechanical and cold stimulation) psychophysical tests were performed intraorally and in the forearm of 27 patients with PTTN and 27 sex- and age-matched controls. The dynamic sensory testing demonstrated less efficient conditioned pain modulation, suggesting reduced function of the inhibitory endogenous pain-modulatory system, in patients with PTTN, mainly in those suffering from the condition for more than a year. The static sensory testing of patients with PTTN demonstrated forearm hyperalgesia to mechanical stimulation mainly in patients suffering from the condition for less than a year and prolonged painful sensation after intraoral cold stimulus mainly in patients suffering from the condition for more than a year. These findings suggest that PTTN is associated more with the inhibitory rather than the facilitatory arm of pain modulation and that the central nervous system has a role in PTTN pathophysiology, possibly in a time-dependent fashion.
Massive stars influence their environment through stellar winds, ionising radiation, and supernova explosions. The efficiency of the energy injection into the interstellar medium (ISM) via bubbles ...and superbubbles is uncertain, and is usually treated as a free parameter for galaxy scale effects. In particular, since many stars are born in groups, it is interesting to study the dependence of the effective energy injection on the concentration of the stars. We aim to reproduce observations of superbubbles, their relation to the energy injection of the parent stars, and to understand their effective energy input into the ISM, as a function of the spatial configuration of the group of parent stars. The Vishniac instability may be responsible for the broadening of the shells of interstellar bubbles. Massive star winds are significant energetically due to their -- in the long run -- more efficient, steady energy injection and because they evacuate the space around the massive stars. For larger scale simulations, the feedback effect of close groups of stars or clusters may be subsumed into one effective energy input with insignificant loss of energy accuracy.
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