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This study sought to conduct a comprehensive search for genetic risk of cognitive decline in the context of geriatric depression.
A genome-wide association study (GWAS) analysis in the Neurocognitive Outcomes of Depression in the Elderly (NCODE) study.
Longitudinal, naturalistic follow-up study.
Older depressed adults, both outpatients and inpatients, receiving care at an academic medical center.
The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) neuropsychological battery was administered to the study participants at baseline and a minimum of twice within a subsequent 3-year period in order to measure cognitive decline. A GWAS analysis was conducted to identify genetic variation that is associated with baseline and change in the CERAD Total Score (CERAD-TS) in NCODE.
The GWAS of baseline CERAD-TS revealed a significant association with an intergenic single-nucleotide polymorphism (SNP) on chromosome 6, rs17662598, that surpassed adjustment for multiple testing (p = 3.7 × 10−7; false discovery rate q = 0.0371). For each additional G allele, average baseline CERAD-TS decreased by 8.656 points. The most significant SNP that lies within a gene was rs11666579 in SLC27A1 (p = 1.1 × 10−5). Each additional copy of the G allele was associated with an average decrease of baseline CERAD-TS of 4.829 points. SLC27A1 is involved with processing docosahexaenoic acid (DHA), an endogenous neuroprotective compound in the brain. Decreased levels of DHA have been associated with the development of Alzheimer’s disease. The most significant SNP associated with CERAD-TS decline over time was rs73240021 in GRXCR1 (p = 1.1 × 10−6), a gene previously linked with deafness. However, none of the associations within genes survived adjustment for multiple testing.
Our GWAS of cognitive function and decline among individuals with late-life depression (LLD) has identified promising candidate genes that, upon replication in other cohorts of LLD, may be potential biomarkers for cognitive decline and suggests DHA supplementation as a possible therapy of interest.
An improved understanding of diagnostic and treatment practices for patients with rare primary mitochondrial disorders can support benchmarking against guidelines and establish priorities for evaluative research. We aimed to describe physician care for patients with mitochondrial diseases in Canada, including variation in care.
We conducted a cross-sectional survey of Canadian physicians involved in the diagnosis and/or ongoing care of patients with mitochondrial diseases. We used snowball sampling to identify potentially eligible participants, who were contacted by mail up to five times and invited to complete a questionnaire by mail or internet. The questionnaire addressed: personal experience in providing care for mitochondrial disorders; diagnostic and treatment practices; challenges in accessing tests or treatments; and views regarding research priorities.
We received 58 survey responses (52% response rate). Most respondents (83%) reported spending 20% or less of their clinical practice time caring for patients with mitochondrial disorders. We identified important variation in diagnostic care, although assessments frequently reported as diagnostically helpful (e.g., brain magnetic resonance imaging, MRI/MR spectroscopy) were also recommended in published guidelines. Approximately half (49%) of participants would recommend “mitochondrial cocktails” for all or most patients, but we identified variation in responses regarding specific vitamins and cofactors. A majority of physicians recommended studies on the development of effective therapies as the top research priority.
While Canadian physicians’ views about diagnostic care and disease management are aligned with published recommendations, important variations in care reflect persistent areas of uncertainty and a need for empirical evidence to support and update standard protocols.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
Groups of student volunteers were immunized with one of five different inactivated influenza virus vaccines. The concentration of virus in the various vaccines differed by both the international unitage test and by the concentration of haemagglutinin, as measured by the single radial diffusion test; the results of the two methods of standardization showed no correlation. The serum HI response to immunization was variable; volunteers given A/England/72 showed a 16·6-fold increase in homologous serum antibody titre whilst volunteers given A/Hong Kong/68 vaccine showed a 4·2-fold increase. The variable response of volunteers to immunization could not be explained by the varied concentration of virus in the vaccines, as measured by either test, the titres of serum HI antibody present before immunization, or a combination of these two factors.
The ability to infect volunteers with WRL 105 virus 4 weeks after immunization with heterologous, inactivated virus vaccine was directly related to the degree of cross-reactivity between the haemagglutinins of this vaccine virus and WRL 105 virus. Thus, the greatest number of infections by the challenge virus were seen in volunteers given A/Hong Kong/68 vaccine, less were observed in volunteers given A/England/72 vaccine, and least were found in groups given A/Port Chalmers/73 or A/Scotland/74 vaccine. However, compared with the incidence of infection in volunteers given B/Hong Kong/73 vaccine, all the heterologous influenza A vaccine gave some immunity to challenge infection.
Interpretation of the Nogahabara I assemblage as a Late Pleistocene abandoned toolkit rests primarily on the premise of a single brief occupation at the site. The limited contextual data presented do not discount a palimpsest of noncontemporaneous assemblages in secondary contexts associated with a lag deposit. Spatial patterning, lithic assemblage patterning, artifact surface alteration, and disparate radiocarbon dates at the site, as well as geological data from the Nogahabara and nearby Kobuk dunes, indicate that the cultural material was subjected to post-depositional disturbance. Alternate hypotheses of site formation and avenues for testing these hypotheses are considered.
Objectives and Methods: Many authors have argued that ethical, legal, and social issues (“ELSIs”) should be explicitly integrated into health technology assessment (HTA), yet doing so poses challenges. This discussion may be particularly salient for technologies viewed as ethically complex, such as genetic screening. Here we provide a brief overview of contemporary discussions of the issues from the HTA literature. We then describe key existing policy evaluation frameworks in the fields of disease screening and public health genomics. Finally, we map the insights from the HTA literature to the policy evaluation frameworks, with discussion of the implications for HTA in genetic screening.
Results and Conclusions: A critical discussion in the HTA literature considers the definition of ELSIs in HTA, highlighting the importance of thinking beyond ELSIs as impacts of technology. Existing HTA guidance on integrating ELSIs relates to three broad approaches: literature synthesis, involvement of experts, and consideration of stakeholder values. The thirteen key policy evaluation frameworks relating to disease screening and public health genomics identified a range of ELSIs relevant to genetic screening. Beyond straightforward impacts of screening, these ELSIs require consideration of factors such as the social and political context surrounding policy decisions. The three broad approaches to addressing ELSIs described above are apparent in the screening/genomics literatures. In integrating these findings we suggest that the method chosen for addressing ELSIs in HTA for genetic screening may determine which ELSIs are prioritized; and that an important challenge is the lack of guidance for evaluating such methods.
Allometric analyses of the three major salivary glands of 44 tammar wallabies Macropus eugenii and 58 parma wallabies Macropus parma from Kawau Island, New Zealand, indicate that tammar wallabies have larger parotid glands while parma wallabies have larger mandibular glands. The difference can be related to the importance of cooling in tammars, an arid-zone species, and the need for greater buffering of forestomach digesta in parma wallabies because of their greater daily food intakes and a higher browse component in their natural diet. Comparisons of sublingual gland size of these two species viewed in terms of their capacity for mucus production suggest that this may be influenced by the need to protect mucosa from mechanical and chemical injury from browse. Sample sizes of brush-tailed rock-wallabies Petrogale pencilliata and swamp wallabies Wallabia bicolor were too small for similar statistical comparisons, but they confirmed that salivary gland histology was broadly similar among all four species.
We have ion implanted a series of dopants into single crystal CdTe. The influence of the impurities on the CdTe has been studied by low temperature photoluminescence spectroscopy. The impurities studied are: O, Cl, Cu, S, Na and Sb, and were selected because of their potential importance in thin film CdTe/CdS photovoltaic devices. Each impurity was implanted to give a smooth gaussian distribution in the first few microns of material with a doping density of 1×1015cm−3. Low temperature photoluminescence spectra were recorded from each sample and compared with an undoped sample. The PL features observed in each sample are discussed and the data is compared to an earlier photoluminescence study of thin film CdTe/CdS photovoltaic device structures.
Tantalum zinc oxide (TZO) with the chemical formula Ta2Zn3O8 can be generated from the reaction of 3 mol ZnO and 1 mol Ta2O5 at elevated temperatures. This phase has been shown to exhibit blue cathodoluminescence at low electron beam voltages. It has also been realized in thin film form on silicon substrate, making TZO an important material for monolithic field emission display devices. The structure type of TZO has been investigated using powder x-ray diffraction techniques. The unit cell of this phase has been determined and found to be monoclinic. These results allow for indexing of the powder pattern first reported by Kasper in 1967 and correct for a discrepancy in the single-crystal structure lattice constants reported by Waburg and Muller-Buschbaum in 1984.
Thin films have been deposited by rf magnetron sputtering from a stoichiometric Ta2Zn3O8 ceramic target (3ZnO + 1Ta2O5). Negative ion re-sputtering effects have been observed in the stoichiometric Ta2Zn3O8 target and have been attributed to O ion formation from primarily Ta-O bonds. Zinc deficient thin films were deposited as a result of the preferential re- sputtering of Zn versus Ta. The negative ion re-sputtering effects are exacerbated at higher powers and lower pressure. This observation is correlated to the oxygen ion transport through the dark space and the plasma, which ultimately controls the energy distribution of the oxygen particles that arrive at the substrate. To circumvent the negative ion re-sputtering, a mosaic ZnO-Ta target was sputtered, which resulted in stoichiometric and luminescent thin films.
The precise birth date of the aerospace composites industry cannot readily be identified; perhaps one should really talk about its rebirth as the first aircraft relied on natural composites such as wood. McMullen gives 1946 as the date that work on cellulose based composites for aircraft use was abandoned in favour of much more stable inorganic reinforcement fibres. This change in the direction of approach was crucial to further developments and can be thought of as marking the start of the aerospace composites industry that can be seen today. Whatever the exact date the industry is now about 50 years old so this golden jubilee edition seems an appropriate place to look at the constraints on the use of composite materials and at recent work at Bristol University aimed at reducing these constraints.
As part of an ongoing investigation to characterize the properties and structure of zinc halide-tellurium oxide glasses, we report preliminary measurements of the optical properties of several Nd- and Er-doped tellurites. Measurements include florescence lifetimes and estimates of the theoretical radiative lifetimes (as obtained by traditional Judd-Ofelt analysis of optical absorption spectra) as well as phonon sideband studies sensitive to vibrational characteristics near the rare earth ion. The response of these optical features to the substitution of alternative halides is examined.
Neutron powder diffraction studies of the layered compounds R1.2Sr1.8Mn2O7, (R = La,Pr, Nd), RSr2Mn2O7 (R = Pr,Nd),and La1.4Sr1.6Mn2O7 show that the degree of distortion of the MnO6 octahcdra do not correlate with the appearance of a metal-insulator (MI) transition in these compounds. Instead, the in-plane Mn-O bond length appears to be a better indicator of the electronic behavior. Detailed bulk magnetization studies on single crystal La1.2Sr1.8Mn2O7 show thai there are three magnetic regimes as a function of temperature: paramagnetic insulator, short-range ordered (SRO) fcrrromangct, and long-range ordered (LRO) fcrromagnct. Scaling analysis indicates that a 2D finite-size XY model is an appropriate description of the magnetic state in the SRO regime.
We present simultaneous energetic electron and solar radio observations from the ISEE−3 spacecraft of several solar type III radio bursts. The UC Berkeley energetic particle experiment measures from 2 to ~ 103 keV with good energy and pitch angle resolution while the Meudon/GSFC radio experiment tracks type III radio bursts at 24 frequencies in the range 30 kHz—2 MHz.
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