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Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
Antipseudomonal carbapenems are an important target for antimicrobial stewardship programs. We evaluated the impact of formulary restriction and preauthorization on relative carbapenem use for medical and surgical intensive care units at a large, urban academic medical center using interrupted time-series analysis.
A national need is to prepare for and respond to accidental or intentional disasters categorized as chemical, biological, radiological, nuclear, or explosive (CBRNE). These incidents require specific subject-matter expertise, yet have commonalities. We identify 7 core elements comprising CBRNE science that require integration for effective preparedness planning and public health and medical response and recovery. These core elements are (1) basic and clinical sciences, (2) modeling and systems management, (3) planning, (4) response and incident management, (5) recovery and resilience, (6) lessons learned, and (7) continuous improvement. A key feature is the ability of relevant subject matter experts to integrate information into response operations. We propose the CBRNE medical operations science support expert as a professional who (1) understands that CBRNE incidents require an integrated systems approach, (2) understands the key functions and contributions of CBRNE science practitioners, (3) helps direct strategic and tactical CBRNE planning and responses through first-hand experience, and (4) provides advice to senior decision-makers managing response activities. Recognition of both CBRNE science as a distinct competency and the establishment of the CBRNE medical operations science support expert informs the public of the enormous progress made, broadcasts opportunities for new talent, and enhances the sophistication and analytic expertise of senior managers planning for and responding to CBRNE incidents.
Optimising short- and long-term outcomes for children and patients with CHD depends on continued scientific discovery and translation to clinical improvements in a coordinated effort by multiple stakeholders. Several challenges remain for clinicians, researchers, administrators, patients, and families seeking continuous scientific and clinical advancements in the field. We describe a new integrated research and improvement network – Cardiac Networks United – that seeks to build upon the experience and success achieved to-date to create a new infrastructure for research and quality improvement that will serve the needs of the paediatric and congenital heart community in the future. Existing gaps in data integration and barriers to improvement are described, along with the mission and vision, organisational structure, and early objectives of Cardiac Networks United. Finally, representatives of key stakeholder groups – heart centre executives, research leaders, learning health system experts, and parent advocates – offer their perspectives on the need for this new collaborative effort.
Functionally graded materials (FGMs) in which the elemental composition intentionally varies with position can be fabricated using directed energy deposition additive manufacturing (AM). This work examines an FGM that is linearly graded from V to Invar 36 (64 wt% Fe, 36 wt% Ni). This FGM cracked during fabrication, indicating the formation of detrimental phases. The microstructure, composition, phases, and microhardness of the gradient zone were analyzed experimentally. The phase composition as a function of chemistry was predicted through thermodynamic calculations. It was determined that a significant amount of the intermetallic σ-FeV phase formed within the gradient zone. When the σ phase constituted the majority phase, catastrophic cracking occurred. The approach presented illustrates the suitability of using equilibrium thermodynamic calculations for the prediction of phase formation in FGMs made by AM despite the nonequilibrium conditions in AM, providing a route for the computationally informed design of FGMs.
The catchments of Pine Island Glacier and Thwaites Glacier in the Amundsen Sea Embayment are two of the largest, most rapidly changing, and potentially unstable sectors of the West Antarctic Ice Sheet. They are also neighboring outlets, separated by the topographically unconfined eastern shear margin of Thwaites Glacier and the southwest tributary of Pine Island Glacier. This tributary begins just downstream of the eastern shear margin and flows into the Pine Island ice shelf. As a result, it is a potential locus of interaction between the two glaciers and could result in cross-catchment feedback during the retreat of either. Here, we analyze relative basal reflectivity profiles from three radar sounding survey lines collected using the UTIG HiCARS radar system in 2004 and CReSIS MCoRDS radar system in 2012 and 2014 to investigate the extent and character of ocean access beneath the southwest tributary. These profiles provide evidence of ocean access ~12 km inland of the 1992–2011 InSAR-derived grounding line by 2014, suggesting either retreat since 2011 or the intrusion of ocean water kilometers inland of the grounding line.
The Taipan galaxy survey (hereafter simply ‘Taipan’) is a multi-object spectroscopic survey starting in 2017 that will cover 2π steradians over the southern sky (δ ≲ 10°, |b| ≳ 10°), and obtain optical spectra for about two million galaxies out to z < 0.4. Taipan will use the newly refurbished 1.2-m UK Schmidt Telescope at Siding Spring Observatory with the new TAIPAN instrument, which includes an innovative ‘Starbugs’ positioning system capable of rapidly and simultaneously deploying up to 150 spectroscopic fibres (and up to 300 with a proposed upgrade) over the 6° diameter focal plane, and a purpose-built spectrograph operating in the range from 370 to 870 nm with resolving power R ≳ 2000. The main scientific goals of Taipan are (i) to measure the distance scale of the Universe (primarily governed by the local expansion rate, H0) to 1% precision, and the growth rate of structure to 5%; (ii) to make the most extensive map yet constructed of the total mass distribution and motions in the local Universe, using peculiar velocities based on improved Fundamental Plane distances, which will enable sensitive tests of gravitational physics; and (iii) to deliver a legacy sample of low-redshift galaxies as a unique laboratory for studying galaxy evolution as a function of dark matter halo and stellar mass and environment. The final survey, which will be completed within 5 yrs, will consist of a complete magnitude-limited sample (i ⩽ 17) of about 1.2 × 106 galaxies supplemented by an extension to higher redshifts and fainter magnitudes (i ⩽ 18.1) of a luminous red galaxy sample of about 0.8 × 106 galaxies. Observations and data processing will be carried out remotely and in a fully automated way, using a purpose-built automated ‘virtual observer’ software and an automated data reduction pipeline. The Taipan survey is deliberately designed to maximise its legacy value by complementing and enhancing current and planned surveys of the southern sky at wavelengths from the optical to the radio; it will become the primary redshift and optical spectroscopic reference catalogue for the local extragalactic Universe in the southern sky for the coming decade.
Evaniid wasps develop as solitary egg predators within the oothecae of cockroaches. Fossil evaniids are relatively common compared with most other parasitoid Hymenoptera, undoubtedly due to their searching for host cockroaches on tree trunks and thus an increased chance of being trapped in tree resin. The genus Parevania Kieffer, 1907 is widely distributed through the Old World and is also known from a small number of rather unremarkable fossil taxa. Here we add to this extinct fauna Parevania oculiseparata Jennings, Krogmann, and Austin new species from Baltic Eocene amber, a species that has highly modified compound eyes that are unique among the Hymenoptera, and possibly among insects as a whole. Parevania oculiseparata n. sp. possesses a prominent acute ridge extending across the entire dorso-ventral elongation of the eye surface. Modifications to the regular curved surface of the eyes are extremely rare among Hymenoptera and previously were only known from two species of Inostemma Haliday, 1833 (Platygastridae s. s.) and the three known species of Isomerala Shipp, 1894 (Eucharitidae). In describing this unusual fossil evaniid species, we also analyze the optical consequences of the eye surface discontinuity, and discuss different types of compound eye modifications that occur in other Hymenoptera and other insects.
A clean hot-water drill was used to gain access to Subglacial Lake Whillans (SLW) in late January 2013 as part of the Whillans Ice Stream Subglacial Access Research Drilling (WISSARD) project. Over 3 days, we deployed an array of scientific tools through the SLW borehole: a downhole camera, a conductivity–temperature–depth (CTD) probe, a Niskin water sampler, an in situ filtration unit, three different sediment corers, a geothermal probe and a geophysical sensor string. Our observations confirm the existence of a subglacial water reservoir whose presence was previously inferred from satellite altimetry and surface geophysics. Subglacial water is about two orders of magnitude less saline than sea water (0.37–0.41 psu vs 35 psu) and two orders of magnitude more saline than pure drill meltwater (<0.002 psu). It reaches a minimum temperature of –0.55~C, consistent with depression of the freezing point by 7.019 MPa of water pressure. Subglacial water was turbid and remained turbid following filtration through 0.45 µm filters. The recovered sediment cores, which sampled down to 0.8 m below the lake bottom, contained a macroscopically structureless diamicton with shear strength between 2 and 6 kPa. Our main operational recommendation for future subglacial access through water-filled boreholes is to supply enough heat to the top of the borehole to keep it from freezing.
Addressing the obesity epidemic depends on a holistic understanding of the reasons that people become and maintain excessive fat. Theories about the causes of obesity usually focus proximately or evoke evolutionary mismatches, with minimal clinical value. There is potential for substantial progress by adapting strategic body mass regulation models from evolutionary ecology to human obesity by assessing the role of information.
Approximately half of the variation in wellbeing measures overlaps with variation in personality traits. Studies of non-human primate pedigrees and human twins suggest that this is due to common genetic influences. We tested whether personality polygenic scores for the NEO Five-Factor Inventory (NEO-FFI) domains and for item response theory (IRT) derived extraversion and neuroticism scores predict variance in wellbeing measures. Polygenic scores were based on published genome-wide association (GWA) results in over 17,000 individuals for the NEO-FFI and in over 63,000 for the IRT extraversion and neuroticism traits. The NEO-FFI polygenic scores were used to predict life satisfaction in 7 cohorts, positive affect in 12 cohorts, and general wellbeing in 1 cohort (maximal N = 46,508). Meta-analysis of these results showed no significant association between NEO-FFI personality polygenic scores and the wellbeing measures. IRT extraversion and neuroticism polygenic scores were used to predict life satisfaction and positive affect in almost 37,000 individuals from UK Biobank. Significant positive associations (effect sizes <0.05%) were observed between the extraversion polygenic score and wellbeing measures, and a negative association was observed between the polygenic neuroticism score and life satisfaction. Furthermore, using GWA data, genetic correlations of -0.49 and -0.55 were estimated between neuroticism with life satisfaction and positive affect, respectively. The moderate genetic correlation between neuroticism and wellbeing is in line with twin research showing that genetic influences on wellbeing are also shared with other independent personality domains.
Impulse control disorders (ICDs) have become a widely recognized non-motor complication of Parkinson's disease (PD) in patients taking dopamine replacement therapy (DRT). There are no current evidence-based recommendations for their treatment, other than reducing their dopaminergic medication.
This study reviews the current literature of the treatment of ICDs including pharmacological treatments, deep brain stimulation, and psychotherapeutic interventions.
Dopamine agonist withdrawal is the most common and effective treatment, but may lead to an aversive withdrawal syndrome or motor symptom degeneration in some individuals. There is insufficient evidence for all other pharmacological treatments in treating ICDs in PD, including amantadine, serotonin selective reuptake inhibitors, antipsychotics, anticonvulsants, and opioid antagonists (e.g. naltrexone). Large randomized control trials need to be performed before these drugs can be routinely used for the treatment of ICDs in PD. Deep brain stimulation remains equivocal because ICD symptoms resolve in some patients after surgery but may appear de novo in others. Cognitive behavioral therapy has been shown to improve ICD symptoms in the only published study, although further research is urgently needed.
Further research will allow for the development of evidence-based guidelines for the management of ICDs in PD.
We discuss the stellar halos of massive elliptical galaxies, as revealed by our ambitious integral-field spectroscopic survey MASSIVE. We show that metallicity drops smoothly as a function of radius out to ~ 2.5 Re, while the [α/Fe] abundance ratios stay flat. The stars in the outskirts likely formed rapidly (to explain the high ratio of alpha to Fe) but in a relatively shallow potential (to explain the low metallicities). This is consistent with expectations for a two-phase growth of massive galaxies, in which the second phase involves accretion of small satellites. We also show some preliminary study of the gas content of these most MASSIVE galaxies.
We analyzed the recent (< 25 yr) spread in New Hampshire, USA, of the exotic tree Kalopanax septemlobus, native to Asia. The invasion was likely initiated by a single tree planted ca. 1972. Our objective was to assess the viability of the invasion, especially in light of the small propagule size. We tallied, mapped, aged, and measured the height and growth of K. septemlobus individuals at two sites, the University of New Hampshire campus (UC) and Thompson Farm (TF), both in Durham. We found over 3,800 plants at UC and 270 at TF in < 120 ha (296 ac) total area. Plant age ranged from 0 to 22 yr, and UC plants were as far as 775 m (2,543 ft) from the purported parent tree. Annual height growth was comparable to midtolerant native trees. Plants occurred in both open and forested habitats, and the mean level of photosynthetically active radiation incident on understory plants was 4 to 6% of full sun. The large population size, shade tolerance, rapid height growth, and ability to sprout from damaged stems suggest potential for K. septemlobus to invade and persist in forests, the most common natural ecosystem in the northeastern United States. We further suggest that small propagule size, likely a single tree, has not prevented K. septemlobus from initiating a spatially extensive and vigorous population. Kalopanax septemlobus has been planted as an ornamental in the northeastern United States, and prevention of region-wide invasion might depend on removal of these trees, even when they occur as single individuals.