To date, there is no validated fluid biomarker for tau pathology in Alzheimer's disease, with contradictory results from studies evaluating the correlation between phosphorylated tau in CSF with tau ...PET imaging. Tau protein is subjected to proteolytic processing into fragments before being secreted to the CSF. A recent study suggested that tau cleavage after amino acid 368 by asparagine endopeptidase (AEP) is upregulated in Alzheimer's disease. We used immunoprecipitation followed by mass spectrometric analyses to evaluate the presence of tau368 species in CSF. A novel Simoa® assay for quantification of tau368 in CSF was developed, while total tau (t-tau) was measured by ELISA and the presence of tau368 in tangles was evaluated using immunohistochemistry. The diagnostic utility of tau368 was first evaluated in a pilot study (Alzheimer's disease = 20, control = 20), then in a second cohort where the IWG-2 biomarker criteria were applied (Alzheimer's disease = 37, control = 45), and finally in a third cohort where the correlation with 18F-GTP1 tau PET was evaluated (Alzheimer's disease = 38, control = 11). The tau368/t-tau ratio was significantly decreased in Alzheimer's disease (P < 0.001) in all cohorts. Immunohistochemical staining demonstrated that tau fragments ending at 368 are present in tangles. There was a strong negative correlation between the CSF tau368/t-tau ratio and 18F-GTP1 retention. Our data suggest that tau368 is a tangle-enriched fragment and that the CSF ratio tau368/t-tau reflects tangle pathology. This novel tau biomarker could be used to improve diagnosis of Alzheimer's disease and to facilitate the development of drug candidates targeting tau pathology. Furthermore, future longitudinal studies will increase our understanding of tau pathophysiology in Alzheimer's disease and other tauopathies.
In most animals, the sex that invests least in its offspring competes more intensely for access to the opposite sex and shows greater development of secondary sexual characters than the sex that ...invests most. However, in some mammals where females are the primary care-givers, females compete more frequently or intensely with each other than males. A possible explanation is that, in these species, the resources necessary for successful female reproduction are heavily concentrated and intrasexual competition for breeding opportunities is more intense among females than among males. Intrasexual competition between females is likely to be particularly intense in cooperative breeders where a single female monopolizes reproduction in each group. Here, we use data from a twelve-year study of wild meerkats (Suricata suricatta), where females show high levels of reproductive skew, to show that females gain greater benefits from acquiring dominant status than males and traits that increase competitive ability exert a stronger influence on their breeding success. Females that acquire dominant status also develop a suite of morphological, physiological and behavioural characteristics that help them to control other group members. Our results show that sex differences in parental investment are not the only mechanism capable of generating sex differences in reproductive competition and emphasize the extent to which competition for breeding opportunities between females can affect the evolution of sex differences and the operation of sexual selection.
The Dark Energy Spectroscopic Instrument (DESI) survey is a spectroscopic survey of tens of millions of galaxies at \(0 < z < 3.5\) covering 14,000 square degrees of the sky. In its first 1.1 years ...of survey operations, it has observed more than 14 million galaxies and 4 million stars. We describe the processes that govern DESI's observations of the 15,000 fields composing the survey. This includes the planning of each night's observations in the afternoon; automatic selection of fields to observe during the night; real-time assessment of field completeness on the basis of observing conditions during each exposure; reduction, redshifting, and quality assurance of each field of targets in the morning following observation; and updates to the list of future targets to observe on the basis of these results. We also compare the performance of the survey with historical expectations and find good agreement. Simulations of the weather and of DESI observations using the real field-selection algorithm show good agreement with the actual observations. After accounting for major unplanned shutdowns, the dark time survey is progressing about 7% faster than forecast, which is good agreement given approximations made in the simulations.
DAHe white dwarfs from the DESI Survey Manser, Christopher J; Gänsicke, Boris T; Inight, Keith ...
Monthly notices of the Royal Astronomical Society,
03/2023, Letnik:
521, Številka:
4
Journal Article
Recenzirano
Odprti dostop
ABSTRACT
A new class of white dwarfs, dubbed DAHe, that present Zeeman-split Balmer lines in emission has recently emerged. However, the physical origin of these emission lines remains unclear. We ...present here a sample of 21 newly identified DAHe systems and determine magnetic field strengths and (for a subset) periods that span the ranges of ≃6.5–147 MG and ≃0.4–36 h, respectively. All but four of these systems were identified from the Dark Energy Spectroscopic Instrument survey sample of more than 47 000 white dwarf candidates observed during its first year of observations. We present detailed analysis of the new DAHe WD J161634.36+541011.51 with a spin period of 95.3 min, which exhibits an anticorrelation between broad-band flux and Balmer line strength that is typically observed for this class of systems. All DAHe systems cluster closely on the Gaia Hertzsprung–Russell diagram where they represent ≃1 per cent of white dwarfs within that region. This grouping further solidifies their unexplained emergence at relatively late cooling times and we discuss this in context of current formation theories. Nine of the new DAHe systems are identifiable from Sloan Digital Sky Survey spectra of white dwarfs that had been previously classified as featureless DC-type systems. We suggest high-S/N (signal-to-noise ratios), unbiased observations of DCs as a possible route for discovering additional DAHe systems.
ABSTRACT
The presence of planetary material in white dwarf atmospheres, thought to be accreted from a dusty debris disc produced via the tidal disruption of a planetesimal, is common. Approximately 5 ...per cent of these discs host a co-orbital gaseous component detectable via emission from atomic transitions – usually the 8600 Å Ca ii triplet. These emission profiles can be highly variable in both morphology and strength. Furthermore, the morphological variations in a few systems have been shown to be periodic, likely produced by an apsidally precessing asymmetric disc. Of the known gaseous debris discs, that around HE 1349–2305 has the most rapidly evolving emission-line morphology, and we present updated spectroscopy of the Ca ii triplet of this system. The additional observations show that the emission-line morphologies vary periodically and consistently, and we constrain the period to two aliases of 459 ± 3 and 502 ± 3 d. We produce images of the Ca ii triplet emission from the disc in velocity space using Doppler tomography – only the second such imaging of a white dwarf debris disc. We suggest that the asymmetric nature of these velocity images is generated by gas moving on eccentric orbits with radially dependent excitation conditions via photoionization from the white dwarf. We also obtained short-cadence (≃4 min) spectroscopy to search for variability on the time-scale of the disc’s orbital period (≃hours) due to the presence of a planetesimal, and rule out variability at a level of ≃1.4 per cent.
•Road study examining an impact of an in-vehicle intersection crossing assist system.•The efficacy of the system was examined across age groups, at a real-world location.•The results showed trends ...towards benefits of the assist system presence.•Older and younger drivers performed similarly, with older being more conservative.
One of the principal facets of age-related decline–diminished perceptual ability, can also be viewed as a prominent factor when crossing intersections, particularly rural intersections that have disproportionately high fatality rate and where vehicles travel at higher velocities. Providing information through in-vehicle technology may aid drivers in improving crossing of such intersections. The current study examines the efficacy of an in-vehicle intersection crossing assist system in a real-world rural setting across age groups. Thirty-two, older and younger drivers completed several crossings of a busy rural intersection. Drivers completed two blocks of trials in which the presence/absence of the in-vehicle system was counterbalanced. The results showed a limited impact of the system on driving performance, exhibited in longer wait time before crossing and rising trend towards reduced probability of accepting small crossing gaps. Older drivers performed similarly to younger, although they showed a greater tendency towards conservative driving behaviour. The current study represents an initial effort to examine an in-vehicle intersection crossing assist system in a real-world rural environment, generating results that reveal a potential for these types of systems to be assistive to drivers across age groups and increase the safety at rural intersections.
Introduction
Effective teamwork plays a critical role in achieving high-performance outcomes in healthcare. Consequently, conducting a comprehensive assessment of team performance is essential for ...providing meaningful feedback during team trainings and enabling comparisons in scientific studies. However, traditional methods like self-reports or behavior observations have limitations such as susceptibility to bias or being resource consuming. To overcome these limitations and gain a more comprehensive understanding of team processes and performance, the assessment of objective measures, such as physiological parameters, can be valuable. These objective measures can complement traditional methods and provide a more holistic view of team performance. The aim of this study was to explore the potential of the use of objective measures for evaluating team performance for research and training purposes. For this, experts in the field of research and medical simulation training were interviewed to gather their opinions, ideas, and concerns regarding this novel approach.
Methods
A total of 34 medical and research experts participated in this exploratory qualitative study, engaging in semi-structured interviews. During the interview, experts were asked for (a) their opinion on measuring team performance with objective measures, (b) their ideas concerning potential objective measures suitable for measuring team performance of healthcare teams, and (c) their concerns regarding the use of objective measures for evaluating team performance. During data analysis responses were categorized per question.
Results
The findings from the 34 interviews revealed a predominantly positive reception of the idea of utilizing objective measures for evaluating team performance. However, the experts reported limited experience in actively incorporating objective measures into their training and research. Nevertheless, they identified various potential objective measures, including acoustical, visual, physiological, and endocrinological measures and a time layer. Concerns were raised regarding feasibility, complexity, cost, and privacy issues associated with the use of objective measures.
Discussion
The study highlights the opportunities and challenges associated with employing objective measures to assess healthcare team performance. It particularly emphasizes the concerns expressed by medical simulation experts and team researchers, providing valuable insights for developers, trainers, researchers, and healthcare professionals involved in the design, planning or utilization of objective measures in team training or research.
Abstract Background & Aims Primary sclerosing cholangitis (PSC) is an orphan hepatobiliary disorder associated with inflammatory bowel disease (IBD). We aimed to estimate the risk of disease ...progression based on distinct clinical phenotypes in a large, international cohort of patients with PSC. Methods We performed a retrospective outcome analysis of patients diagnosed with PSC from 1980 through 2010 at 37 centers in Europe, North America, and Australia. For each patient, we collected data on sex, clinician-reported age at and date of PSC and IBD diagnoses, phenotypes of IBD and PSC, and date and indication of IBD-related surgeries. The primary and secondary endpoints were liver transplantation or death (LTD) and hepatopancreatobiliary malignancy, respectively. Cox proportional hazards models were applied to determine the effects of individual covariates on rates of clinical events, with time-to-event analysis ascertained through Kaplan-Meier estimates. Results Of the 7121 patients in the cohort, 2616 met the primary endpoint (median time-to-event of 14.5 years) and 721 developed hepatopancreatobiliary malignancy. The most common malignancy was cholangiocarcinoma (n=594); patients of advanced age at diagnosis had an increased incidence, compared with younger patients (incidence rate IR: 1.2 per 100 patient-years for patients younger than 20 years old, 6.0 per 100 patient-years for patients 21–30 years old, 9.0 per 100 patient-years for patients 31–40 years old, 14.0 per 100 patient-years for patients 41–50 years old, 15.2 per 100 patient-years for patients 51–60 years old, and 21.0 per 100 patient-years for patients older than 60 years). Of all patients with PSC studied, 65.5% were men, 89.8% had classical or large-duct disease, and 70.0% developed IBD at some point. Assessing the development of IBD as a time-dependent covariate, Crohn’s disease (CD) and no IBD (both vs ulcerative colitis UC) were associated with a lower risk of LTD (unadjusted hazard ratio HR, 0.62; P <.001 and HR, 0.90; P =.03; respectively) and malignancy (HR, 0.68; P =.008 and HR, 0.77; P =.004, respectively). Small-duct PSC was associated with a lower risk of LTD or malignancy compared with classic PSC (HR, 0.30 and HR, 0.15, respectively; both P <.001). Female sex was also associated with a lower risk of LTD or malignancy (HR, 0.88; P =.002 and HR, 0.68; P <.001, respectively). In multivariable analyses assessing the primary endpoint, small-duct PSC characterized a low-risk phenotype in both sexes (adjusted HR for men, 0.23; P <.001 and adjusted HR for women, 0.48; P =.003). Conversely, patients with UC had an increased risk of liver disease progression compared to patients with CD (HR, 1.56; P <.001) or no IBD (HR, 1.15; P =.002). Conclusions In an analysis of data from individual patients with PSC worldwide, we found significant variation in clinical course associated with age at diagnosis, sex, and ductal- and IBD subtypes. The survival estimates provided might be used to estimate risk levels for patients with PSC and select patients for clinical trials.
Despite thousands of spectroscopic detections, only four isolated white dwarfs exhibit Balmer emission lines. The temperature inversion mechanism is a puzzle over 30 years old that has defied ...conventional explanations. One hypothesis is a unipolar inductor that achieves surface heating via ohmic dissipation of a current loop between a conducting planet and a magnetic white dwarf. To investigate this model, new time-resolved spectroscopy, spectropolarimetry, and photometry of the prototype GD 356 are studied. The emission features vary in strength on the rotational period, but in anti-phase with the light curve, consistent with a cool surface spot beneath an optically thin chromosphere. Possible changes in the line profiles are observed at the same photometric phase, potentially suggesting modest evolution of the emission region, while the magnetic field varies by 10 per cent over a full rotation. These comprehensive data reveal neither changes to the photometric period, nor additional signals such as might be expected from an orbiting body. A closer examination of the unipolar inductor model finds points of potential failure: the observed rapid stellar rotation will inhibit current carriers due to the centrifugal force, there may be no supply of magnetospheric ions, and no anti-phase flux changes are expected from ohmic surface heating. Together with the highly similar properties of the four cool, emission-line white dwarfs, these facts indicate that the chromospheric emission is intrinsic. A tantalizing possibility is that intrinsic chromospheres may manifest in (magnetic) white dwarfs, and in distinct parts of the HR diagram based on structure and composition.
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