Accelerated telomere length attrition has been associated with psychological stress and early adversity in adults; however, no studies have examined whether telomere length in childhood is associated ...with early experiences. The Bucharest Early Intervention Project is a unique randomized controlled trial of foster care placement compared with continued care in institutions. As a result of the study design, participants were exposed to a quantified range of time in institutional care, and represented an ideal population in which to examine the association between a specific early adversity, institutional care and telomere length. We examined the association between average relative telomere length, telomere repeat copy number to single gene copy number (T/S) ratio and exposure to institutional care quantified as the percent of time at baseline (mean age 22 months) and at 54 months of age that each child lived in the institution. A significant negative correlation between T/S ratio and percentage of time was observed. Children with greater exposure to institutional care had significantly shorter relative telomere length in middle childhood. Gender modified this main effect. The percentage of time in institutional care at baseline significantly predicted telomere length in females, whereas the percentage of institutional care at 54 months was strongly predictive of telomere length in males. This is the first study to demonstrate an association between telomere length and institutionalization, the first study to find an association between adversity and telomere length in children, and contributes to the growing literature linking telomere length and early adversity.
Bapineuzumab, a humanized anti-amyloid-beta (Abeta) monoclonal antibody for the potential treatment of Alzheimer disease (AD), was evaluated in a multiple ascending dose, safety, and efficacy study ...in mild to moderate AD.
The study enrolled 234 patients, randomly assigned to IV bapineuzumab or placebo in 4 dose cohorts (0.15, 0.5, 1.0, or 2.0 mg/kg). Patients received 6 infusions, 13 weeks apart, with final assessments at week 78. The prespecified primary efficacy analysis in the modified intent-to-treat population assumed linear decline and compared treatment differences within dose cohorts on the Alzheimer's Disease Assessment Scale-Cognitive and Disability Assessment for Dementia. Exploratory analyses combined dose cohorts and did not assume a specific pattern of decline.
No significant differences were found in the primary efficacy analysis. Exploratory analyses showed potential treatment differences (p < 0.05, unadjusted for multiple comparisons) on cognitive and functional endpoints in study "completers" and APOE epsilon4 noncarriers. Reversible vasogenic edema, detected on brain MRI in 12/124 (9.7%) bapineuzumab-treated patients, was more frequent in higher dose groups and APOE epsilon4 carriers. Six vasogenic edema patients were asymptomatic; 6 experienced transient symptoms.
Primary efficacy outcomes in this phase 2 trial were not significant. Potential treatment differences in the exploratory analyses support further investigation of bapineuzumab in phase 3 with special attention to APOE epsilon4 carrier status.
Due to varying doses and a lack of statistical precision, this Class II ascending dose trial provides insufficient evidence to support or refute a benefit of bapineuzumab.
A low ankle brachial index (ABI) indicates atherosclerosis and an increased risk of cardiovascular and cerebrovascular events. Screening for a low ABI can identify an asymptomatic higher risk group ...potentially amenable to preventive treatments.
To determine the effectiveness of aspirin in preventing events in people with a low ABI identified on screening the general population.
The Aspirin for Asymptomatic Atherosclerosis trial was an intention-to-treat double-blind randomized controlled trial conducted from April 1998 to October 2008, involving 28,980 men and women aged 50 to 75 years living in central Scotland, free of clinical cardiovascular disease, recruited from a community health registry, and had an ABI screening test. Of those, 3350 with a low ABI (< or = 0.95) were entered into the trial, which was powered to detect a 25% proportional risk reduction in events.
Once daily 100 mg aspirin (enteric coated) or placebo.
The primary end point was a composite of initial fatal or nonfatal coronary event or stroke or revascularization. Two secondary end points were (1) all initial vascular events defined as a composite of a primary end point event or angina, intermittent claudication, or transient ischemic attack; and (2) all-cause mortality.
After a mean (SD) follow-up of 8.2 (1.6) years, 357 participants had a primary end point event (13.5 per 1000 person-years, 95% confidence interval CI, 12.2-15.0). No statistically significant difference was found between groups (13.7 events per 1000 person-years in the aspirin group vs 13.3 in the placebo group; hazard ratio HR, 1.03; 95% CI, 0.84-1.27). A vascular event comprising the secondary end point occurred in 578 participants (22.8 per 1000 person-years; 95% CI, 21.0-24.8) and no statistically significant difference between groups (22.8 events per 1000 person-years in the aspirin group vs 22.9 in the placebo group; HR, 1.00; 95% CI, 0.85-1.17). There was no significant difference in all-cause mortality between groups (176 vs 186 deaths, respectively; HR, 0.95; 95% CI, 0.77-1.16). An initial event of major hemorrhage requiring admission to hospital occurred in 34 participants (2.5 per 1000 person-years) in the aspirin group and 20 (1.5 per 1000 person-years) in the placebo group (HR, 1.71; 95% CI, 0.99-2.97).
Among participants without clinical cardiovascular disease, identified with a low ABI based on screening a general population, the administration of aspirin compared with placebo did not result in a significant reduction in vascular events.
isrctn.org Identifier: ISRCTN66587262.
Ultrahigh energy neutrinos are interesting messenger particles since, if detected, they can transmit exclusive information about ultrahigh energy processes in the Universe. These particles, with ...energies above 10 super(16)eV , interact very rarely. Therefore, detectors that instrument several gigatons of matter are needed to discover them. The ARA detector is currently being constructed at the South Pole. It is designed to use the Askaryan effect, the emission of radio waves from neutrino-induced cascades in the South Pole ice, to detect neutrino interactions at very high energies. With antennas distributed among 37 widely separated stations in the ice, such interactions can be observed in a volume of several hundred cubic kilometers. Currently three deep ARA stations are deployed in the ice, of which two have been taking data since the beginning of 2013. In this article, the ARA detector "as built" and calibrations are described. Data reduction methods used to distinguish the rare radio signals from overwhelming backgrounds of thermal and anthropogenic origin are presented. Using data from only two stations over a short exposure time of 10 months, a neutrino flux limit of 1.5x10 super(-6)GeV/cm super(2)/s/sr is calculated for a particle energy of 10 super(18)eV , which offers promise for the full ARA detector.
Cognitive decline is a feared aspect of growing old. It is a major contributor to lower quality of life and loss of independence in old age. We investigated the genetic contribution to individual ...differences in nonpathological cognitive ageing in five cohorts of older adults. We undertook a genome-wide association analysis using 549 692 single-nucleotide polymorphisms (SNPs) in 3511 unrelated adults in the Cognitive Ageing Genetics in England and Scotland (CAGES) project. These individuals have detailed longitudinal cognitive data from which phenotypes measuring each individual's cognitive changes were constructed. One SNP--rs2075650, located in TOMM40 (translocase of the outer mitochondrial membrane 40 homolog)--had a genome-wide significant association with cognitive ageing (P=2.5 × 10(-8)). This result was replicated in a meta-analysis of three independent Swedish cohorts (P=2.41 × 10(-6)). An Apolipoprotein E (APOE) haplotype (adjacent to TOMM40), previously associated with cognitive ageing, had a significant effect on cognitive ageing in the CAGES sample (P=2.18 × 10(-8); females, P=1.66 × 10(-11); males, P=0.01). Fine SNP mapping of the TOMM40/APOE region identified both APOE (rs429358; P=3.66 × 10(-11)) and TOMM40 (rs11556505; P=2.45 × 10(-8)) as loci that were associated with cognitive ageing. Imputation and conditional analyses in the discovery and replication cohorts strongly suggest that this effect is due to APOE (rs429358). Functional genomic analysis indicated that SNPs in the TOMM40/APOE region have a functional, regulatory non-protein-coding effect. The APOE region is significantly associated with nonpathological cognitive ageing. The identity and mechanism of one or multiple causal variants remain unclear.
DTI is increasingly being used as a measure to study tissue damage in several neurologic diseases. Our aim was to investigate the comparability of DTI measures between different MR imaging magnets ...and platforms.
Two healthy volunteers underwent DTI on five 3T MR imaging scanners (3 Trios and 2 Signas) by using a matched 33 noncollinear diffusion-direction pulse sequence. Within each subject, a total of 16 white matter (corpus callosum, periventricular, and deep white matter) and gray matter (cortical and deep gray) ROIs were drawn on a single image set and then were coregistered to the other images. Mean FA, ADC, and longitudinal and transverse diffusivities were calculated within each ROI. Concordance correlations were derived by comparing ROI DTI values among each of the 5 magnets.
Mean concordance for FA was 0.96; for both longitudinal and transverse diffusivities, it was 0.93; and for ADC, it was 0.88. Mean scan-rescan concordance was 0.96-0.97 for all DTI measures. Concordance correlations within platforms were, in general, better than those between platforms for all DTI measures (mean concordance of 0.96).
We found that a 3T magnet and high-angular-resolution pulse sequence yielded comparable DTI measurements across different MR imaging magnets and platforms. Our results indicate that FA is the most comparable measure across magnets, followed by individual diffusivities. The comparability of DTI measures between different magnets supports the feasibility of multicentered clinical trials by using DTI as an outcome measure.
The Antarctic Impulsive Transient Antenna, a NASA long-duration balloon payload, searches for radio emission from interactions of ultrahigh-energy neutrinos in polar ice. The third flight of the ...Antarctic Impulsive Transient Antenna was launched in December 2014 and completed a 22-day flight. We present the results of three analyses searching for Askaryan radio emission of neutrino origin. In the most sensitive of the analyses, we find one event in the signal region on an expected background of 0.7−0.3+0.5. Though consistent with the background estimate, the event remains compatible with a neutrino hypothesis even after additional postunblinding scrutiny.
Recently, the ANITA collaboration reported on two upward-going extensive air shower events consistent with a primary particle that emerges from the surface of the Antarctic ice sheet. These events ...may be of ν τ origin, in which the neutrino interacts within the Earth to produce a τ lepton that emerges from the Earth, decays in the atmosphere, and initiates an extensive air shower. In this paper we estimate an upper bound on the ANITA acceptance to a diffuse ν τ flux detected via τ -lepton-induced air showers within the bounds of standard model uncertainties. By comparing this estimate with the acceptance of Pierre Auger Observatory and IceCube and assuming standard model interactions, we conclude that a ν τ origin of these events would imply a neutrino flux at least two orders of magnitude above current bounds.
The ANtarctic Impulsive Transient Antenna (ANITA) NASA long-duration balloon payload completed its fourth flight in December 2016, after 28 days of flight time. ANITA is sensitive to impulsive ...broadband radio emission from interactions of ultrahigh-energy neutrinos in polar ice (Askaryan emission). We present the results of two separate blind analyses searching for signals from Askaryan emission in the data from the fourth flight of ANITA. The more sensitive analysis, with a better expected limit, has a background estimate of 0.64−0.45+0.69 and an analysis efficiency of 82±2%. The second analysis has a background estimate of 0.34−0.16+0.66 and an analysis efficiency of 71±6%. Each analysis found one event in the signal region, consistent with the background estimate for each analysis. The resulting limit further tightens the constraints on the diffuse flux of ultrahigh-energy neutrinos at energies above 1019.5 eV.
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