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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.
The US Agency for Healthcare Research and Quality (AHRQ) Evidence-based Practice Center (EPC) program sponsors the development of systematic reviews to inform clinical policy and practice. The EPC program sought to better understand how health systems identify and use this evidence.
Representatives from eleven EPCs, the EPC Scientific Resource Center, and AHRQ developed a semi-structured interview script to query a diverse group of nine Key Informants (KIs) involved in health system quality, safety and process improvement about how they identify and use evidence. Interviews were transcribed and qualitatively summarized into key themes.
All KIs reported that their organizations have either centralized quality, safety, and process improvement functions within their system, or they have partnerships with other organizations to conduct this work. There was variation in how evidence was identified, with larger health systems having medical librarians and central bureaus to gather and disseminate information and smaller systems having local chief medical officers or individual clinicians do this work. KIs generally prefer guidelines, especially those with treatment algorithms, because they are actionable. They like systematic reviews because they efficiently condense study results and reconcile conflicting data. They prefer information from systematic reviews to be presented as short digestible summaries with the full report available on demand. KIs preferred systematic reviews from reputable entities and those without commercial bias. Some of the challenges KIs reported include how to resolve conflicting evidence, the generalizability of evidence to local needs, determining whether the evidence is up-to-date, and the length of time required to generate reviews. The topics of greatest interest included predictive analytics, high-value care, advance care planning, and care coordination. To increase awareness of AHRQ EPC reviews, KIs suggest alerting people at multiple levels in a health-system when new evidence reports are available and making reports easier to find in common search engines.
Systematic reviews are valued by health system leaders. To be most useful they should be easy to locate and available in different formats targeted to the needs of different audiences.
A controversy at the 2016 IUCN World Conservation Congress on the topic of closing domestic ivory markets (the 007, or so-called James Bond, motion) has given rise to a debate on IUCN's value proposition. A cross-section of authors who are engaged in IUCN but not employed by the organization, and with diverse perspectives and opinions, here argue for the importance of safeguarding and strengthening the unique technical and convening roles of IUCN, providing examples of what has and has not worked. Recommendations for protecting and enhancing IUCN's contribution to global conservation debates and policy formulation are given.
Near ice shelves around Antarctica the ocean becomes supercooled and has been observed to carry small suspended ice crystals. Our measurements demonstrate that these small crystals are persistently present in the water column beneath the winter fast ice, and when incorporated in sea ice they reduce the mean grain size of the sea-ice cover. By midwinter, larger ice crystals below the ice/water interface are observed to form a porous sub-ice platelet layer with an ice volume fraction of 0.25 ± 0.06. The magnitude and direction of the oceanic heat flux varied between (5 ± 6) Wm-2 (upwards) and (-15 ± 10) Wm-2 (downwards) in May, but by September it settled between (-6 ± 2) and (-11 ± 2) W m-2. The negative values imply that the ocean acts as a heat sink which is responsible for the growth of 12% of the ice thickness between June and September. This oceanic contribution should not be ignored in models of Antarctic sea-ice thickness close to an ice shelf.
Population III has been invoked to explain the missing mass in the haloes of galaxies, the first heavy elements in our Galaxy and even to explain the whole microwave background. However there are alternative explanations for each of these phenomena. The most compelling evidence for the existence of a pregalactic generation of objects is the observed distortion of the microwave background in the millimetre range, which can be explained as radiation from Population III objects absorbed and re-emitted by dust grains. If the distortion is confirmed, we can probably conclude that the density fluctuations in the early universe were isothermal and that no neutrino can have a mass in the astrophysically interesting range 1–100 eV.
The contributions to the far infrared spectra of galaxies of the ‘cool’ cirrus and ‘warm’ starburst components are reviewed, together with the complications introduced by dust in the narrow-line regions of Seyferts, the destruction of very small grains, and the small percentage of galaxies which are optically thick in the optical band. The role of interactions and mergers in generating ultraluminous infrared galaxies is reviewed.
Excavations at Abreu Garcia provide a detailed case study of a mound and enclosure mortuary complex used by the southern proto-Jê in the southern Brazilian highlands. The recovery of 16 secondary cremation deposits within a single mound allows an in-depth discussion of spatial aspects of mortuary practices. A spatial division in the placement of the interments adds another level of duality to the mortuary landscape, which comprises: (1) paired mound and enclosures, (2) twin mounds within a mound and enclosure, and (3) the dual division in the mound interior. The multiple levels of nested asymmetric dualism evoke similarities to the moiety system that characterizes modern southern Jê groups, highlighting both the opposition and the complementarity of the social system. The findings offer deeper insight into fundamental aspects of southern proto-Jê social organization, including the dual nature of the community, the manifestation of social structure in the landscape, and its incorporation into mortuary ritual. The results have implications for research design and developing appropriate methodologies to answer culture-specific questions. Furthermore, the parallels among archaeology, ethnohistory, and ethnography enable an understanding of the foundation of modern descendent groups and an assessment of the continuity in indigenous culture beyond European contact.
New strain data relating to flexural oscillations of the Erebus Glacier Tongue (EGT), McMurdo Sound, Antarctica, are presented and are analysed in the frequency domain. The data were collected during November 1989, just 3 months prior to the most recent calving of the ice tongue which occurred in March 1990. A broad-band oscillation centred on 50 s is found in both the strain measurements collected on the EGT and those collected on the sea ice nearby. The oscillation is shown, at least in part, to be propagating with a phase velocity of approximately 65 ms−1 in a direction away from the snout towards the grounding line, rather than being wholly due to a standing-wave pattern in the EGT. A coupling model between the sea ice and the EGT is proposed and is shown to compare reasonably well with the data.
Stonehenge is a site that continues to yield surprises. Excavation in 2009 added a new and unexpected feature: a smaller, dismantled stone circle on the banks of the River Avon, connected to Stonehenge itself by the Avenue. This new structure has been labelled ‘Bluestonehenge’ from the evidence that it once held a circle of bluestones that were later removed to Stonehenge. Investigation of the Avenue closer to Stonehenge revealed deep periglacial fissures within it. Their alignment on Stonehenge's solstitial axis (midwinter sunset–midsummer sunrise) raises questions about the early origins of this ritual landscape.
Infrared wavelengths are free of several of the problems that plague optical galaxy surveys. At high galactic latitude ≥99% of 60μ sources in the IRAS Point Source Catalog, after deletion of obvious stars, are galaxies. At lower latitudes care has to be taken to avoid confusion with emission from interstellar dust (the ‘cirrus’). IRAS galaxies have been used to determined the direction of the gravitational acceleration acting on the Local Group due to galaxies and clusters within about 200 Mpc. This agrees well with the direction of the microwave background dipole. The density of matter in the universe, distributed like IRAS galaxies, needed to account for the observed velocity of the Local Group, corresponds to Ωo = 1.0 ± 0.2. In the standard hot Big Bang model, 90–95% of this matter would have to be non-baryonic.
IRAS galaxies are significantly less clustered than optically selected galaxy samples.
A simple and versatile parametrized approach to the star formation history allows a quantitative investigation of the constraints from far infrared and submillimetre counts and background intensity measurements.
The models include four spectral components: infrared cirrus, an M 82-like starburst, an Arp 220-like starburst and an AGN dust torus. The 60 μm luminosity function is determined for each chosen rate of evolution using the PSCz redshift data for 15000 galaxies. The proportions of each spectral type as a function of 60 μm luminosity are chosen for consistency with IRAS and SCUBA colour-luminosity relations, and with the fraction of AGN as a function of luminosity found in 12 μm samples.
A good fit to the observed counts at 0.44, 2.2, 15, 60, 90, 175 and 850 μm can be found with pure luminosity evolution in all 3 cosmological models investigated: Ω0 = 1, Ω0 = 0.3 (Λ = 0), and Ω0 = 0.3, Λ = 0.7. All 3 models also give an acceptable fit to the integrated background spectrum. The total mass-density of stars generated in all 3 cosmological models is consistent with that observed.
Library consortia navigate a course between providing benefit to their member institutions through a range of collaborative activities and opportunities and, in return, requiring financial and in-kind commitments to sustain the consortium. Deriving benefit from library collaboration usually entails obligations from each participant, such as long-term commitment to programmes, active engagement of library leadership and staff in the management and co-ordination of activities, and both direct and indirect financial commitments to the consortium and the programmes it operates on members’ behalf.
The commitment implicit in any form of formal library collaboration can be twofold. On the one hand, members of a consortium have a commitment to the entity or organization set up to manage and co-ordinate a collaborative enterprise on their behalf, while on the other hand there is a commitment directly to the other participants in the collaborative activity. For example, a certain level of spending commitment may be required for a library to participate in a consortial acquisitions exercise, or a commitment to provide access to library collections may be a prerequisite of a collaborative resource-sharing or inter-lending programme. Such commitment may demand that a participating library undertake not just a share in the consortium's costs or management, but a degree of compromise and risk in committing and adhering to collaborative programmes and activities in the long term. Potentially, there is an inherent risk in collaboration, in so far as the object of the collaboration or the actions taken to achieve it may fail or may depart from the original aims. There is also a potential for compromise, in that an individual member may need to make concessions so as to accommodate the broader needs or interests of the group.
The value of collaborative library activity may also vary over time as the assumptions on which a joint enterprise is undertaken are undermined, for example, by systemic changes to the types of resources and services that the library offers and the way in which these are delivered, or by the opportunities that arise from technological or environmental changes and their potential to supersede the collaborative enterprise, or by the demands and imperatives set by parent institutions to demonstrate value and return on investment.
Understanding who is most vulnerable during an earthquake will help health care responders prepare for future disasters. We analyzed the demography of casualties from the Christchurch earthquake in New Zealand.
The demography of the total deceased, injured, and hospitalized casualties of the Christchurch earthquake was compared with that of the greater Christchurch population, the Christchurch central business district working population, and patients who presented to the single acute emergency department on the same month and day over the prior 10 years. Sex data were compared to scene of injury, context of injury, clinical characteristics of injury, and injury severity scores.
Significantly more females than males were injured or killed in the entire population of casualties (P<0.001). Most of the deceased and hospitalized casualties were injured in the central business district (171/182 deceased [94%]; 33/91 hospitalized [36.2%]). Approximately half of both sexes were injured at home (1002/2032 males [49%]; 2390/4627 females [52%]) and >20% were injured at commercial or service localities (444/2032 males [22%]; 1105/4627 females [24%]). Adults aged between 20 and 69 years (1639/2032 males [81%]; 3717/4627 females [80%]) were most frequently injured.
Where people were and what they were doing at the time of the earthquake influenced their risk of injury. (Disaster Med Public Health Preparedness. 2016;10:67-73)
Memory clinics, typically led by multidisciplinary teams and requiring health professional referral, are one means of providing diagnosis and care coordination for dementia. Nurse-led clinics may provide an effective and alternative means to dementia diagnosis, and open referral policies may minimize existing barriers to accessing a diagnosis, but evidence is needed.
Patients attending a one-day per week nurse-led memory clinic over a 25-month period during 2011–2013 (n = 106) completed comprehensive cognitive assessments and were diagnosed by an aged care nurse practitioner. Descriptive statistics detail the demographics, assessment scores, and diagnostic profiles of patients. Comparable data from published literature was identified, and the differences were analyzed qualitatively.
One hundred and six patients were assessed with the key differences from other data sets being history of falls more common, higher mean Mini-Mental State Examination scores, and fewer dementia diagnoses. Sixty-four patients (60%) were self-referred to the nurse-led memory clinic, of which 19 (30%) were diagnosed with mild cognitive impairment (MCI) or dementia. Overall, forty-eight patients (45%) received diagnoses of MCI or dementia.
An open referral policy led to a high proportion of patients being self-referred, and nearly a third of these were diagnosed with cognitive impairment or dementia. Open referral policies and nurse-led services may overcome some of the barriers to early diagnosis that are currently experienced. Considering an aging population worldwide and the associated increases in cognitive impairment, which benefits from early identification and intervention, this paper provides an alternative model of nurse-led assessment.