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The global ageing population and the long prodromal period for the development of cognitive decline and dementia brings a need to understand the antecedents of both successful and impaired cognitive ageing. It is increasingly apparent that the trajectory of risk-factor change, as well as the level of the risk factor, may be associated with an increased or decreased risk of cognitive decline or dementia.
Our aim was to summarise the published evidence and to generate hypotheses related to risk-factor trajectories and risk of incident cognitive decline or dementia.
We collated data from longitudinal observational studies relating to trajectory of blood pressure, obesity and cholesterol and later cognitive decline or dementia using standard systematic review methodology. The databases MEDLINE, Embase and PsycINFO were searched from inception to 26 April 2018.
Thirteen articles were retained for inclusion. Analytical methods varied. Our summary of the current evidence base suggests that first body mass index and then blood pressure rises and then falls more steeply in those who go on to develop dementia. The evidence for cholesterol was less consistent.
Based on our review we present the hypothesis that weight falls around 10 years and blood pressure around 5 years before diagnosis. Confirmatory work is required. However, characterisation of risk according to combinations and patterns of risk factors may ultimately be integrated into the assessments used to identify those at risk of receiving a diagnosis of cognitive decline or dementia in late life.
Fast ice flow is associated with the deformation of subglacial sediment. Seismic shear velocities, Vs, increase with the rigidity of material and hence can be used to distinguish soft sediment from hard bedrock substrates. Depth profiles of Vs can be obtained from inversions of Rayleigh wave dispersion curves, from passive or active-sources, but these can be highly ambiguous and lack depth sensitivity. Our novel Bayesian transdimensional algorithm, MuLTI, circumvents these issues by adding independent depth constraints to the inversion, also allowing comprehensive uncertainty analysis. We apply MuLTI to the inversion of a Rayleigh wave dataset, acquired using active-source (Multichannel Analysis of Surface Waves) techniques, to characterise sediment distribution beneath the frontal margin of Midtdalsbreen, an outlet of Norway's Hardangerjøkulen ice cap. Ice thickness (0–20 m) is constrained using co-located GPR data. Outputs from MuLTI suggest that partly-frozen sediment (Vs 500–1000 m s−1), overlying bedrock (Vs 2000–2500 m s−1), is present in patches with a thickness of ~4 m, although this approaches the resolvable limit of our Rayleigh wave frequencies (14–100 Hz). Uncertainties immediately beneath the glacier bed are <280 m s−1, implying that MuLTI cannot only distinguish bedrock and sediment substrates but does so with an accuracy sufficient for resolving variations in sediment properties.
Introduction: Our team developed “The Ottawa Troponin Pathway” (OTP) for Non-ST Elevation Myocardial Infarction (NSTEMI) diagnosis using serial conventional troponin (cTnI) 3 hours apart to aid in safe and early disposition of ED patients. The primary objective of this study is to validate the diagnostic accuracy of the OTP in the cohort of patients with cTnI values above the 99th percentile ( > 45ng/L). Methods: This study is a health records review conducted at the Civic and General Campuses of The Ottawa Hospital from August 2017 to December 2017. Adults (≥18 years) who presented to the ED with symptoms of ACS, and who had serial cTnI (at least two values 3 hours ±15 minutes apart) performed for diagnosis of NSTEMI and at least one cTnI value > 45ng/L were included. Patients with cardiac arrest, STEMI, unstable angina or those with TnI values ≤45ng/L were excluded. The outcomes were death due to unknown cause or NSTEMI adjudicated by two blinded investigators within 30 days. Data collected include baseline characteristics, ED management, length of stay, cTnI values and times of measurement, disposition, and outcome. We used descriptive statistics and test diagnostic characteristics to analyze our data. Results: We screened 53,077 patients, of whom 635 patients were included in the study (mean age 71.6 years; 57.6% males; 59.7% hospitalized; median ED length of stay 4.7 hours.). 107 patients (16.9%; 95%CI 14.1%-20.0%) were diagnosed with NSTEMI within 30 days. Among patients with TNI values above the 99th percentile, the OTP did not miss any patients diagnosed with NSTEMI. The sensitivity and the specificity of the OTP were 100% (95%CI 96.6%-100%) and 32.2% (95%CI 28.2%-36.4%) respectively. Conclusion: Our results show that the OTP is diagnostically accurate in ruling out NSTEMI among patients with cTNI values above the 99th percentile with symptoms concerning for ACS. Using the OTP will allow for early referral to consulting services for management, safe and early discharge home, and improve ED crowding.
A cluster of Salmonella Paratyphi B variant L(+) tartrate(+) infections with indistinguishable pulsed-field gel electrophoresis patterns was detected in October 2015. Interviews initially identified nut butters, kale, kombucha, chia seeds and nutrition bars as common exposures. Epidemiologic, environmental and traceback investigations were conducted. Thirteen ill people infected with the outbreak strain were identified in 10 states with illness onset during 18 July–22 November 2015. Eight of 10 (80%) ill people reported eating Brand A raw sprouted nut butters. Brand A conducted a voluntary recall. Raw sprouted nut butters are a novel outbreak vehicle, though contaminated raw nuts, nut butters and sprouted seeds have all caused outbreaks previously. Firms producing raw sprouted products, including nut butters, should consider a kill step to reduce the risk of contamination. People at greater risk for foodborne illness may wish to consider avoiding raw products containing raw sprouted ingredients.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
Coups d’état, once a common end for democracies in the Americas, have declined sharply in recent years. This article investigates whether overall public support for coups is also in decline. Examining 21 countries in Latin America and the Caribbean from 2004 to 2014 helps to evaluate two alternative theses on democratization: Mainwaring and Pérez-Liñán’s 2013 normative regime preferences theory, which inquires (but does not test) whether public opinion can signal to elites a reluctance or willingness to support a coup; and classic modernization theory (Inglehart 1988; Inglehart and Welzel 2005). We find a substantively meaningful effect of democratic attitudes on coup support and a weak effect for national wealth, from which we infer that evolving elite values and preferences are paralleled at the mass level and that together, those two trends play a stronger role in the consolidation of democratic regimes than does modernization.
Observationally locating the position of the H2O snowline in protoplanetary disks is crucial for understanding planetesimal and planet formation processes, and the origin of water on the Earth. In our studies, we conducted calculations of chemical reactions and water line profiles in protoplanetary disks, and identified that ortho/para-H216O, H218O lines with small Einstein A coefficients and relatively high upper state energies are dominated by emission from the hot midplane region inside the H2O snowline. Therefore, through analyzing their line profiles the position of the H2O snowline can be located. Moreover, because the number density of the H218O is much smaller than that of H216O, the H218O lines can trace deeper into the disk and thus they are potentially better probes of the exact position of the H2O snowline in disk midplane.
Antimicrobials play a critical role in treating cases of invasive non-typhoidal salmonellosis (iNTS) and other diseases, but efficacy is hindered by resistant pathogens. Selection for phenotypical resistance may occur via several mechanisms. The current study aims to identify correlations that would allow indirect selection of increased resistance to ceftriaxone, ciprofloxacin and azithromycin to improve antimicrobial stewardship. These are medically important antibiotics for treating iNTS, but these resistances persist in non-Typhi Salmonella serotypes even though they are not licensed for use in US food animals. A set of 2875 Salmonella enterica isolates collected from animal sources by the National Antimicrobial Resistance Monitoring System were stratified in to 10 subpopulations based on serotype and host species. Collateral resistances in each subpopulation were estimated as network models of minimum inhibitory concentration partial correlations. Ceftriaxone sensitivity was correlated with other β-lactam resistances, and less commonly resistances to tetracycline, trimethoprim-sulfamethoxazole or kanamycin. Azithromycin resistance was frequently correlated with chloramphenicol resistance. Indirect selection for ciprofloxacin resistance via collateral selection appears unlikely. Density of the ACSSuT subgraph resistance aligned well with the phenotypical frequency. The current study identifies several important resistances in iNTS serotypes and further research is needed to identify the causative genetic correlations.
The Neotoma Paleoecology Database is a community-curated data resource that supports interdisciplinary global change research by enabling broad-scale studies of taxon and community diversity, distributions, and dynamics during the large environmental changes of the past. By consolidating many kinds of data into a common repository, Neotoma lowers costs of paleodata management, makes paleoecological data openly available, and offers a high-quality, curated resource. Neotoma’s distributed scientific governance model is flexible and scalable, with many open pathways for participation by new members, data contributors, stewards, and research communities. The Neotoma data model supports, or can be extended to support, any kind of paleoecological or paleoenvironmental data from sedimentary archives. Data additions to Neotoma are growing and now include >3.8 million observations, >17,000 datasets, and >9200 sites. Dataset types currently include fossil pollen, vertebrates, diatoms, ostracodes, macroinvertebrates, plant macrofossils, insects, testate amoebae, geochronological data, and the recently added organic biomarkers, stable isotopes, and specimen-level data. Multiple avenues exist to obtain Neotoma data, including the Explorer map-based interface, an application programming interface, the neotoma R package, and digital object identifiers. As the volume and variety of scientific data grow, community-curated data resources such as Neotoma have become foundational infrastructure for big data science.
OBJECTIVES/SPECIFIC AIMS: Clinical guidelines recommend using predicted atherosclerotic cardiovascular disease (ASCVD) risk to inform treatment decisions. The objective was to compare the contribution of changes in modifiable risk factors Versus aging to the development of high 10-year predicted ASCVD risk. METHODS/STUDY POPULATION: Prospective follow-up of the Jackson Heart Study, an exclusively African-American cohort, at visit 1 (2000–2004) and visit 3 (2009–2012). Analyses included 1115 African-American participants without a high 10-year predicted ASCVD risk (<7.5%), hypertension, diabetes, or ASCVD at visit 1. We used the Pooled Cohort equations to calculate the incidence of high (≥7.5%) 10-year predicted ASCVD risk at visit 3. We recalculated the percentage with a high 10-year predicted ASCVD risk at visit 3 assuming each risk factor [age, systolic blood pressure (SBP), antihypertensive medication use, diabetes, smoking, total and high-density lipoprotein cholesterol], one at a time, did not change from visit 1. RESULTS/ANTICIPATED RESULTS: The mean age at visit 1 was 45.2±9.5 years. Overall, 30.9% (95% CI 28.3%–33.4%) of participants developed high 10-year predicted ASCVD risk. Aging accounted for 59.7% (95% CI 54.2%–65.1%) of the development of high 10-year predicted ASCVD risk compared with 32.8% (95% CI 27.0%–38.2%) for increases in SBP or antihypertensive medication initiation and 12.8% (95% CI 9.6%–16.5%) for incident diabetes. Among participants <50 years, the contribution of increases in SBP or antihypertensive medication initiation was similar to aging. DISCUSSION/SIGNIFICANCE OF IMPACT: Increases in SBP and antihypertensive medication initiation are major contributors to the development of high 10-year predicted ASCVD risk in African Americans, particularly among younger adults.
The Protoplanetary Discussions conference—held in Edinburgh, UK, from 2016 March 7th–11th—included several open sessions led by participants. This paper reports on the discussions collectively concerned with the multi-physics modelling of protoplanetary discs, including the self-consistent calculation of gas and dust dynamics, radiative transfer, and chemistry. After a short introduction to each of these disciplines in isolation, we identify a series of burning questions and grand challenges associated with their continuing development and integration. We then discuss potential pathways towards solving these challenges, grouped by strategical, technical, and collaborative developments. This paper is not intended to be a review, but rather to motivate and direct future research and collaboration across typically distinct fields based on community-driven input, to encourage further progress in our understanding of circumstellar and protoplanetary discs.
The Amdeh Formation is a 3.4 km stack of sparsely fossiliferous quartzites and shales which crops out in the Al Hajar mountains near Muscat. Here we describe the uppermost member (Am5) that can be dated biostratigraphically as Darriwilian and which is the outcrop equivalent, and probably the seaward continuation, of the Saih Nihayda Formation in the Ghaba Salt Basin of northern Oman. The outcrops at Wadi Daiqa and Hayl al Quwasim consist of 690 m of quartzitic sandstones, shales and bivalve-rich shell beds. Trace fossils referable to the Cruziana and Skolithos ichnofacies abound. The member comprises storm-dominated shelf, shoreface and delta deposits. A number of new discoveries have been made in the outcrops: fragments of the arandaspid fish Sacabambaspis, ossicles and moulds of the early disparid crinoid Iocrinus, two new genera of conodont, an occurrence of the rare trinucleid trilobite Yinpanolithus, and palynological and sedimentological evidence of more continuous Floian–Darriwilian deposition than is usual in the region. Sea levels during Middle Ordovician time are estimated to have been 50–200 m above present levels and a wide, low-gradient shelf covered much of Arabia. Similar trace fossils and storm-dominated, micro-tidal, sedimentary rocks occur throughout the region. Small changes of sea level, possibly caused by the growth and melting of polar ice sheets, could lead to substantial seaward or landward shifts of facies belts. The Am5 deposits are thick compared to most equivalents in Arabia implying active subsidence and a ready supply of sediment.
The fundamental reason for the presence of peatlands is a positive balance between plant production and decomposition of organic matter. Organic matter accumulates in these systems because prolonged waterlogged conditions result in soil anoxia (i.e. exclusion of oxygen), and under these conditions decomposition rates can be lower than those of primary production, as seen in Figure 8.1. Climate therefore plays an important role in peat accumulation, both directly by affecting plant productivity and decomposition of organic matter, and indirectly through its effects on hydrology, water balance and vegetation composition (for a summary, refer to Yu, Beilman and Jones (2009)). Climate provides broad-scale controls on peatland extent, types and vegetation, and ultimately, ecosystem services such as carbon sequestration and storage, as well as water and hazard regulation (Chapters 4 and 5). Peatlands can therefore play a vital role in ecosystem-based adaptation in helping society mitigate and adapt to climate change.
Future climate change is likely to alter the hydrology and soil temperature of peatlands, with far-reaching consequences for their biodiversity, ecology and biogeochemistry, and interactions with the Earth system. For example, the possibility of drier conditions allowing peat erosion and increases in CO2 emissions that would result in a positive feedback to climate change (Turetsky 2010). Peatlands that have been damaged by human activity are more vulnerable to climate-induced changes in hydrology and temperature, but suitable management strategies may make them more resilient to changes and help to stabilise the delivery of ecosystem services (Chapter 1).
This chapter describes the interactions between climate and peatlands in three sections. The first section explains how present climate influences peatlands, by documenting how climate limits peatland geographical extent globally, and how bioclimatic envelope models can predict peatland extent. We indicate how each type of peatland is linked to a specific climate range, and introduce the concept of how climate controls peatland ecosystem function and services. The second section looks into the past. It describes how peat preserves a record of past climates and environmental conditions that can be deciphered to reveal the history of peatland vegetation, hydrology and carbon accumulation changes in relation to past changes in climate. We highlight lessons that can be learned from the palaeo-record preserved in peat.
Background: Acute flaccid paralysis (AFP) is notifiable in Canada with a differential diagnosis that includes a number of conditions. This analysis describes the epidemiology of AFP in Canadian youth less than 15 years old. Methods: Monthly active surveillance for AFP was conducted as part of the Canadian AFP Surveillance System. Results: From 1996 to 2014, 850 cases of AFP were reported, representing an average annual crude incidence rate of 0.77 cases per 100,000 youth less than 15 years old. The mean age of cases was 6.8 years (median 5.9 years). Nine percent had an abnormal neurological history and 53% had an acute respiratory illness within 30 days of onset. Fever occurred in 23% of cases, 96% experienced bilateral weakness, 21% had respiratory muscle involvement, and 26% had cranial nerve involvement. The average hospital length of stay was 13.5 days. The most common diagnoses were Guillain-Barré Syndrome (GBS) or a variant (70%), and transverse myelitis (TM, 14%). At the time of the initial report, 14% had fully recovered. Conclusions: Our AFP surveillance system provides a baseline for AFP and its causes in the Canadian paediatric population. While rare, AFP is associated with severe morbidity in youth. GBS and TM were the most common diagnoses.
Mapping combined with till provenance studies have resulted in a re-appraisal of the pre-Devensian glacial stratigraphy of Norfolk, England. The traditional model invoked two formations, a North Sea Drift Formation (NSDF) overlain by a Lowestoft Formation, formed by co-existing ice-sheets originating in Scandinavia and Northern Britain respectively. The NSDF included three diamictons, the First, Second and Third Cromer tills. The Briton’s Lane Sands and Gravels were considered to overlie the Lowestoft Formation. However, our work has shown this stratigraphy to be untenable, and we propose a model of several glaciations instead of co-existing ice-sheets. In our revised stratigraphy, the oldest formation, the Happisburgh Formation (including the Happisburgh or First Cromer Till) includes massive, sandy tills derived from northern Britain. The overlying Lowestoft Formation, including the Second Cromer (Walcott) Till is confirmed as derived from the west, introducing much Jurassic material as well as Chalk. The Sheringham Cliffs Formation includes both brown sandy tills (the Third Cromer Till) and ‘marly drift’, in a variety of tectonic relationships, and derived from the north and NNW. Finally the Briton’s Lane Formation is the only formation to include Scandinavian erratics. Dating of the four formations is at varying levels of confidence, with the Lowestoft Formation most confidently confirmed as MIS 12. The Happisburgh Formation is believed to represent an earlier glaciation, and MIS 16 is proposed. The Sheringham Cliffs Formation is tentatively believed to date from MIS 10, and the Briton’s Lane Formation is assigned to MIS 6.
Among dialysis facilities participating in a bloodstream infection (BSI) prevention collaborative, access-related BSI incidence rate improvements observed immediately following implementation of a bundle of BSI prevention interventions were sustained for up to 4 years. Overall, BSI incidence remained unchanged from baseline in the current analysis.
The collective response of electrons in an ultrathin foil target irradiated by an ultraintense (
) laser pulse is investigated experimentally and via 3D particle-in-cell simulations. It is shown that if the target is sufficiently thin that the laser induces significant radiation pressure, but not thin enough to become relativistically transparent to the laser light, the resulting relativistic electron beam is elliptical, with the major axis of the ellipse directed along the laser polarization axis. When the target thickness is decreased such that it becomes relativistically transparent early in the interaction with the laser pulse, diffraction of the transmitted laser light occurs through a so called ‘relativistic plasma aperture’, inducing structure in the spatial-intensity profile of the beam of energetic electrons. It is shown that the electron beam profile can be modified by variation of the target thickness and degree of ellipticity in the laser polarization.