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The present study explored relationships among personality, Alzheimer’s disease (AD) biomarkers, and dementia by addressing the following questions: (1) Does personality discriminate healthy aging and earliest detectable stage of AD? (2) Does personality predict conversion from healthy aging to early-stage AD? (3) Do AD biomarkers mediate any observed relationships between personality and dementia status/conversion?
Both self- and informant ratings of personality were obtained in a large well-characterized longitudinal sample of cognitively normal older adults (N = 436) and individuals with early-stage dementia (N = 74). Biomarkers included amyloid imaging, hippocampal volume, cerebral spinal fluid (CSF) Aβ42, and CSF tau.
Higher neuroticism, lower conscientiousness, along with all four biomarkers strongly discriminated cognitively normal controls from early-stage AD individuals. The direct effects of neuroticism and conscientiousness were only mediated by hippocampal volume. Conscientiousness along with all biomarkers predicted conversion from healthy aging to early-stage AD; however, none of the biomarkers mediated the relationship between conscientiousness and conversion. Conscientiousness predicted conversion as strongly as the biomarkers, with the exception of hippocampal volume.
Conscientiousness and to a lesser extent neuroticism serve as important independent behavioral markers for AD risk.
Soft matter has historically been an unlikely candidate for investigation by electron microscopy techniques due to damage by the electron beam as well as inherent instability under a high vacuum environment. Characterization of soft matter has often relied on ensemble-scattering techniques. The recent development of cryogenic transmission electron microscopy (cryo-TEM) provides the soft matter community with an exciting opportunity to probe the structure of soft materials in real space. Cryo-TEM reduces beam damage and allows for characterization in a native, frozen-hydrated state, providing direct visual representation of soft structure. This article reviews cryo-TEM in soft materials characterization and illustrates how it has provided unique insights not possible by traditional ensemble techniques. Soft matter systems that have benefited from the use of cryo-TEM include biological-based “soft” nanoparticles (e.g., viruses and conjugates), synthetic polymers, supramolecular materials as well as the organic–inorganic interface of colloidal nanoparticles. Many challenges remain, such as combining structural and chemical analyses; however, the opportunity for soft matter research to leverage newly developed cryo-TEM techniques continues to excite.
Measuring the elastic and plastic properties with nanoindentation is predicated on the indentation not fracturing the material. In this study, an unloading curve analysis is used to identify indentation-induced fracture in brittle molecular organic crystals to define conditions, where properties measurements are accurate, and for calculating the toughness. Single crystals of cyclotetramethylene tetranitramine (HMX) and idoxuridine were indented from 1 to 300 mN with indenter probes of varying acuity to identify fracture initiation loads. Idoxuridine displayed no fracture up to and at 100 mN, with fracture occurrence then seen at an increasing rate until every indentation made induced fracture at 300 mN. HMX displayed no fracture up to and at 4 mN, with fracture then occurring at an increasing rate until every sample fractured at 8 mN. The toughness of HMX and idoxuridine is ≈0.28 ≈ 0.4–0.5 MPa/m1/2, respectively.
Wind-driven snow redistribution can increase the spatial heterogeneity of snow accumulation on ice caps and ice sheets, and may prove crucial for the initiation and survival of glaciers in areas of marginal glaciation. We present a snowdrift model (Snow_Blow), which extends and improves the model of Purves, Mackaness and Sugden (1999, Journal of Quaternary Science 14, 313–321). The model calculates spatial variations in relative snow accumulation that result from variations in topography, using a digital elevation model (DEM) and wind direction as inputs. Improvements include snow redistribution using a flux routing algorithm, DEM resolution independence and the addition of a slope curvature component. This paper tests Snow_Blow in Antarctica (a modern environment) and reveals its potential for application in palaeoenvironmental settings, where input meteorological data are unavailable and difficult to estimate. Specifically, Snow_Blow is applied to the Ellsworth Mountains in West Antarctica where ablation is considered to be predominantly related to wind erosion processes. We find that Snow_Blow is able to replicate well the existing distribution of accumulating snow and snow erosion as recorded in and around Blue Ice Areas. Lastly, a variety of model parameters are tested, including depositional distance and erosion vs wind speed, to provide the most likely input parameters for palaeoenvironmental reconstructions.
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 initial classic Fontan utilising a direct right atrial appendage to pulmonary artery anastomosis led to numerous complications. Adults with such complications may benefit from conversion to a total cavo-pulmonary connection, the current standard palliation for children with univentricular hearts.
A single institution, retrospective chart review was conducted for all Fontan conversion procedures performed from July, 1999 through January, 2017. Variables analysed included age, sex, reason for Fontan conversion, age at Fontan conversion, and early mortality or heart transplant within 1 year after Fontan conversion.
A total of 41 Fontan conversion patients were identified. Average age at Fontan conversion was 24.5 ± 9.2 years. Dominant left ventricular physiology was present in 37/41 (90.2%) patients. Right-sided heart failure occurred in 39/41 (95.1%) patients and right atrial dilation was present in 33/41 (80.5%) patients. The most common causes for Fontan conversion included atrial arrhythmia in 37/41 (90.2%), NYHA class II HF or greater in 31/41 (75.6%), ventricular dysfunction in 23/41 (56.1%), and cirrhosis or fibrosis in 7/41 (17.1%) patients. Median post-surgical follow-up was 6.2 ± 4.9 years. Survival rates at 30 days, 1 year, and greater than 1-year post-Fontan conversion were 95.1, 92.7, and 87.8%, respectively. Two patients underwent heart transplant: the first within 1 year of Fontan conversion for heart failure and the second at 5.3 years for liver failure.
Fontan conversion should be considered early when atrial arrhythmias become common rather than waiting for severe heart failure to ensue, and Fontan conversion can be accomplished with an acceptable risk profile.
Current surveillance for healthcare-associated (HA) urinary tract infection (UTI) is focused on catheter-associated infection with hospital onset (HO-CAUTI), yet this surveillance does not represent the full burden of HA-UTI to patients. Our objective was to measure the incidence of potentially HA, community-onset (CO) UTI in a retrospective cohort of hospitalized patients.
Retrospective cohort study.
Academic, quaternary care, referral center.
Hospitalized adults at risk for HA-UTI from May 2009 to December 2011 were included.
Patients who did not experience a UTI during the index hospitalization were followed for 30 days post discharge to identify cases of potentially HA-CO UTI.
We identified 3,273 patients at risk for potentially HA-CO UTI. The incidence of HA-CO UTI in the 30 days post discharge was 29.8 per 1,000 patients. Independent risk factors of HA-CO UTI included paraplegia or quadriplegia (adjusted odds ratio [aOR], 4.6; 95% confidence interval [CI], 1.2–18.0), indwelling catheter during index hospitalization (aOR, 1.5; 95% CI, 1.0–2.3), prior piperacillin-tazobactam prescription (aOR, 2.3; 95% CI, 1.1–4.5), prior penicillin class prescription (aOR, 1.7; 95% CI, 1.0–2.8), and private insurance (aOR, 0.6; 95% CI, 0.4–0.9).
HA-CO UTI may be common within 30 days following hospital discharge. These data suggest that surveillance efforts may need to be expanded to capture the full burden to patients and better inform antibiotic prescribing decisions for patients with a history of hospitalization.
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.
Environmental risk factors for dementia are poorly understood. Aluminium and fluorine in drinking water have been linked with dementia but uncertainties remain about this relationship.
In the largest longitudinal study in this context, we set out to explore the individual effect of aluminium and fluoride in drinking water on dementia risk and, as fluorine can increase absorption of aluminium, we also examine any synergistic influence on dementia.
We used Cox models to investigate the association between mean aluminium and fluoride levels in drinking water at their residential location (collected 2005–2012 by the Drinking Water Quality Regulator for Scotland) with dementia in members of the Scottish Mental Survey 1932 cohort who were alive in 2005.
A total of 1972 out of 6990 individuals developed dementia by the linkage date in 2012. Dementia risk was raised with increasing mean aluminium levels in women (hazard ratio per s.d. increase 1.09, 95% CI 1.03–1.15, P < 0.001) and men (1.12, 95% CI 1.03–1.21, P = 0.004). A dose-response pattern of association was observed between mean fluoride levels and dementia in women (1.34, 95% CI 1.28–1.41, P < 0.001) and men (1.30, 95% CI 1.22–1.39, P < 0.001), with dementia risk more than doubled in the highest quartile compared with the lowest. There was no statistical interaction between aluminium and fluoride levels in relation with dementia.
Higher levels of aluminium and fluoride were related to dementia risk in a population of men and women who consumed relatively low drinking-water levels of both.
To enhance enrollment into randomized clinical trials (RCTs), we proposed electronic health record-based clinical decision support for patient–clinician shared decision-making about care and RCT enrollment, based on “mathematical equipoise.”
As an example, we created the Knee Osteoarthritis Mathematical Equipoise Tool (KOMET) to determine the presence of patient-specific equipoise between treatments for the choice between total knee replacement (TKR) and nonsurgical treatment of advanced knee osteoarthritis.
With input from patients and clinicians about important pain and physical function treatment outcomes, we created a database from non-RCT sources of knee osteoarthritis outcomes. We then developed multivariable linear regression models that predict 1-year individual-patient knee pain and physical function outcomes for TKR and for nonsurgical treatment. These predictions allowed detecting mathematical equipoise between these two options for patients eligible for TKR. Decision support software was developed to graphically illustrate, for a given patient, the degree of overlap of pain and functional outcomes between the treatments and was pilot tested for usability, responsiveness, and as support for shared decision-making.
The KOMET predictive regression model for knee pain had four patient-specific variables, and an r2 value of 0.32, and the model for physical functioning included six patient-specific variables, and an r2 of 0.34. These models were incorporated into prototype KOMET decision support software and pilot tested in clinics, and were generally well received.
Use of predictive models and mathematical equipoise may help discern patient-specific equipoise to support shared decision-making for selecting between alternative treatments and considering enrollment into an RCT.
Cognitive impairment is a core feature of psychotic disorders, but the profile of impairment across adulthood, particularly in African-American populations, remains unclear.
Using cross-sectional data from a case–control study of African-American adults with affective (n = 59) and nonaffective (n = 68) psychotic disorders, we examined cognitive functioning between early and middle adulthood (ages 20–60) on measures of general cognitive ability, language, abstract reasoning, processing speed, executive function, verbal memory, and working memory.
Both affective and nonaffective psychosis patients showed substantial and widespread cognitive impairments. However, comparison of cognitive functioning between controls and psychosis groups throughout early (ages 20–40) and middle (ages 40–60) adulthood also revealed age-associated group differences. During early adulthood, the nonaffective psychosis group showed increasing impairments with age on measures of general cognitive ability and executive function, while the affective psychosis group showed increasing impairment on a measure of language ability. Impairments on other cognitive measures remained mostly stable, although decreasing impairments on measures of processing speed, memory and working memory were also observed.
These findings suggest similarities, but also differences in the profile of cognitive dysfunction in adults with affective and nonaffective psychotic disorders. Both affective and nonaffective patients showed substantial and relatively stable impairments across adulthood. The nonaffective group also showed increasing impairments with age in general and executive functions, and the affective group showed an increasing impairment in verbal functions, possibly suggesting different underlying etiopathogenic mechanisms.
Annually dated tree-rings of 509 live and deadwood limber pine (Pinus flexilis) samples from the semi-arid Wassuk Range, Nevada, yielded a 3996-yr record extending from 1983 BC to AD 2013. Correlations of radial growth with climate were positive for water relations and negative for summer temperatures. Long-term trends of ring-width corresponded to climate variability documented from other proxies, including low growth during the Late Holocene Dry Period and Medieval Climate Anomaly (MCA) and elevated growth during cool, wet periods of the Neoglacial and Little Ice Age. Spline fit of the data indicated that growth decrease in the last 20 years was second lowest on record, surpassed by lowest growth at 20 BC—AD 150. Demographics of limber pine by aspect and elevation were not strongly related to long-term climate dynamics, except in the case of extirpations on all but north aspects at the end of the MCA. Pines occurred persistently on north aspects, where a continuous record existed to present. Elevation shifts were not obvious on any aspect, and no evidence existed for migration above current treeline. Non-climatic factors appear to interact with climate to make north slopes refugial for upland pines in semi-arid regions across four millennia.
This paper examines retirement saving policy for independent – or contingent – workers, a growing segment of the workforce. Because few of these workers are covered by employer-sponsored retirement plans, they often do not benefit from payroll deduction, employer matching contributions, automatic enrollment, and other provisions that encourage retirement saving. Better use of fintech, judicious changes to tax policy, and expanded Automatic IRAs would help independent workers save for retirement. In addition, we propose the creation of retirement saving accounts that attach to the worker as a supplement to, and possible replacement for, the current system of employer-sponsored accounts.
The aim of this work is to provide new information about the history of astronomical science and the efforts of the people that have enriched our discipline, often coming from anonymity. Here we compile the attempts made in our country to prove the theory of General Relativity through experiments that, as they were without success, fell into oblivion.
India was still a British colony when the International Astronomical Union was born in 1919. India did not have a national science academy nor a national research council at the time. The Royal Society, London, which was the adhering body of Great Britain to IAU, handled matters of the colony too. India formally joined the IAU in 1948 as an independent nation through an initiative taken by the Government of India. In 1968, the National Institute of Sciences of India (NISI) became the adhering organisation to the IAU, as did the other affiliate Unions of ICSU. Soon after, its name was changed to Indian National Science Academy (INSA).
Till the nineteen-sixties, individual Indian membership in the IAU grew rather tardily but the situation changed with the rapid growth of astronomical activities in the country. In 1967, M.K. Vainu Bappu, the then Director of the Kodaikanal Observatory, was elected a Vice-President of the Union. In 1979, he was elected the President of IAU for the triennium 1979–1982, and during the same period, V. Radhakrishnan and Govind Swarup were elected Presidents respectively of the Commisions 34 and 40. In 1985, the General Assembly of the Union was held in New Delhi. It was dedicated to the memory of Vainu Bappu who had initiated the process of inviting the Union to hold its GA in India. A few years later the Sixth Asian-Pacific Regional IAU Meeting was held in Pune. A number of IAU symposia and colloquia have also been held in the country. During the last three decades, the engagement of the Indian astronomers with IAU has increased a great deal with a large number of them taking on important official roles in the IAU. Currently, India has close to 300 individual members.
Breakthrough Listen is a 10-yr initiative to search for signatures of technologies created by extraterrestrial civilisations at radio and optical wavelengths. Here, we detail the digital data recording system deployed for Breakthrough Listen observations at the 64-m aperture CSIRO Parkes Telescope in New South Wales, Australia. The recording system currently implements two modes: a dual-polarisation, 1.125-GHz bandwidth mode for single-beam observations, and a 26-input, 308-MHz bandwidth mode for the 21-cm multibeam receiver. The system is also designed to support a 3-GHz single-beam mode for the forthcoming Parkes ultra-wideband feed. In this paper, we present details of the system architecture, provide an overview of hardware and software, and present initial performance results.
Seafloor geodetic studies such as Global Positioning System (GPS)-Acoustic experiments often require the measurement platform on the sea surface to be positioned accurately to within a few centimetres. In this paper, we test the utility of Precise Point Positioning (PPP) for this application with two experiments. The first fixed platform experiment is a comparison between three independent processing software packages: Positioning and Navigation Data Analyst (PANDA), Global Navigation Satellite System-Inferred Positioning System and Orbit Analysis Simulation Software (GIPSY-OASIS), and the Canadian Spatial Reference System (CSRS)) and a more accurate solution based on conventional differential processing of a remote GPS station in the Aleutian Islands. The second moving platform experiment is a comparison among the three PPP software packages using 40 hours of ship navigation data collected during the Roger Revelle RR1605 cruise 170 nautical miles southwest of Palau in May 2016. We found the PPP solutions were repeatable to 5·49 cm in the horizontal components and 12·4 cm in the vertical component. This demonstrates not only that PPP is a useful tool for positioning marine platforms in remote locations, but also that modern ship navigation instruments such as the Kongsberg Seapath 330 + are suitable for seafloor geodetic application.