Rationale
Adult‐onset asthma differs from childhood‐onset asthma in many respects. It is more heterogeneous, often severe and frequently associated with loss of lung function. To identify underlying ...mechanisms of adult‐onset asthma and to capture predictors of disease progression, detailed characterization and phenotyping is necessary.
Objectives
To characterize adult‐onset asthma and identify subphenotypes of adult‐onset asthma.
Methods
A cohort of 200 patients with adult‐onset (>18 year) asthma (age 54 (26–75) year) was recruited from one academic and three nonacademic pulmonary outpatient clinics in Amsterdam, the Netherlands. These patients were fully characterized with respect to clinical, functional and inflammatory markers. After data reduction, K‐means nonhierarchical cluster analysis was performed to identify clusters of adult‐onset asthma.
Measurements and main results
Patients with adult‐onset asthma were predominately female (61%) and nonatopic (55%). Within this group of patients were identified three clusters of adult‐onset asthma. Cluster 1 (n = 69) consisted of patients with severe eosinophilic inflammation‐predominant asthma and persistent airflow limitation despite high‐intensity anti‐inflammatory treatment, with relatively low symptom scores. The second cluster was characterized by obese women with frequent symptoms, high healthcare utilization and low sputum eosinophils. The third cluster consisted of patients with mild‐to‐moderate, well‐controlled asthma with normal lung function and low inflammatory markers. Repeatability accuracy was 98.2%.
Conclusions
Amongst patients with adult‐onset asthma, three subphenotypes can be identified with distinct clinical and inflammatory characteristics. These subphenotypes help to understand the underlying pathobiology and provide clinicians with directions for personalized management.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Familial hypercholesterolemia is marked by very elevated low-density lipoprotein cholesterol levels and premature cardiovascular disease. This 20-year follow-up study showed that statin initiation ...during childhood in affected persons slowed the progression of carotid intima–media thickness and reduced the risk of cardiovascular disease in adulthood.
Maintenance of high physical performance during aging might be supported by an adequate dietary intake of niacin, vitamins B-6 and B-12, and folate because these B vitamins are involved in multiple ...processes related to muscle functioning. However, not much is known about the association between dietary intake of these B vitamins and physical performance.
The objectives of this study were to investigate the association between dietary intake of niacin, vitamins B-6 and B-12, and folate and physical performance in older adults and to explore mediation by niacin status and homocysteine concentrations.
We used baseline data from the New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe (NU-AGE) trial, which included n = 1249 healthy older adults (aged 65–79 y) with complete data on dietary intake measured with 7-d food records and questionnaires on vitamin supplement use and physical performance measured with the short physical performance battery and handgrip dynamometry. Associations were assessed by adjusted linear mixed models.
Intake of vitamin B-6 was related to lower chair rise test time β: –0.033 ± 0.016 s (log); P = 0.043. Vitamin B-6 intake was also significantly associated with handgrip strength, but for this association, a significant interaction effect between vitamin B-6 intake and physical activity level was found. In participants with the lowest level of physical activity, higher intake of vitamin B-6 tended to be associated with greater handgrip strength (β: 1.5 ± 0.8 kg; P = 0.051), whereas in participants in the highest quartile of physical activity, higher intake was associated with lower handgrip strength (β: –1.4 ± 0.7 kg; P = 0.041). No evidence was found for an association between intake of niacin, vitamin B-12, or folate and physical performance or for mediation by niacin status or homocysteine concentrations.
Vitamin B-6 intake was associated with better chair rise test time in a population of European healthy older adults and also with greater handgrip strength in participants with low physical activity only. Homocysteine concentrations did not mediate these associations. The NU-AGE trial was registered at clinicaltrials.gov as NCT01754012.
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CMK, GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We discuss the properties of 137 cataclysmic variables (CVs) which are included in the Sloan Digital Sky Survey (SDSS) spectroscopic data base, and for which accurate orbital periods have been ...measured. 92 of these systems are new discoveries from SDSS and were followed-up in more detail over the past few years. 45 systems were previously identified as CVs because of the detection of optical outbursts and/or X-ray emission, and subsequently re-identified from the SDSS spectroscopy. The period distribution of the SDSS CVs differs dramatically from that of all the previously known CVs, in particular it contains a significant accumulation of systems in the orbital period range 80–86 min. We identify this feature as the elusive ‘period minimum spike’ predicted by CV population models, which resolves a long-standing discrepancy between compact binary evolution theory and observations. We show that this spike is almost entirely due to the large number of CVs with very low accretion activity identified by SDSS. The optical spectra of these systems are dominated by emission from the white dwarf photosphere, and display little or no spectroscopic signature from the donor stars, suggesting very low mass companion stars. We determine the average absolute magnitude of these low-luminosity CVs at the period minimum to be 〈Mg〉= 11.6 ± 0.7. Comparison of the SDSS CV sample to the CVs found in the Hamburg Quasar Survey and the Palomar Green Survey suggests that the depth of SDSS is the key ingredient resulting in the discovery of a large number of intrinsically faint short-period systems.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
White dwarfs are often found in binary systems with orbital periods ranging from tens of minutes to hours in which they can accrete gas from their companion stars. In about 15 per cent of these ...binaries, the magnetic field of the white dwarf is strong enough (at 10
gauss or more) to channel the accreted matter along field lines onto the magnetic poles. The remaining systems are referred to as 'non-magnetic', because until now there has been no evidence that they have a magnetic field that is strong enough to affect the accretion dynamics. Here we report an analysis of archival optical observations of the 'non-magnetic' accreting white dwarf in the binary system MV Lyrae, whose light curve displays quasi-periodic bursts of about 30 minutes duration roughly every 2 hours. The timescale and amplitude of these bursts indicate the presence of an unstable, magnetically regulated accretion mode, which in turn implies the existence of magnetically gated accretion, in which disk material builds up around the magnetospheric boundary (at the co-rotation radius) and then accretes onto the white dwarf, producing bursts powered by the release of gravitational potential energy. We infer a surface magnetic field strength for the white dwarf in MV Lyrae of between 2 × 10
gauss and 1 × 10
gauss, too low to be detectable by other current methods. Our discovery provides a new way of studying the strength and evolution of magnetic fields in accreting white dwarfs and extends the connections between accretion onto white dwarfs, young stellar objects and neutron stars, for which similar magnetically gated accretion cycles have been identified.
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IJS, KISLJ, NUK, SBMB, UL, UM, UPUK
Machine vision technology has been used in automated body condition score (BCS) classification of dairy cows. The current vision-based classifications use information acquired from a limited number ...of body regions of the cow. Our study aimed to improve automated BCS classification by including multiple body condition–related features extracted from 3 viewpoints in 8 body regions. The data set of this study included 44 lactating cows with their BCS evenly distributed over the scale of BCS from 1.5 to 4.5 units. The body images of these cows were recorded over 2 consecutive days using 3-dimensional cameras positioned to view the cow from the top, right side, and rear. Each image was automatically processed to identify anatomical landmarks on the body surface. Around these anatomical landmarks, the bony prominences and body surface depressions were quantified to describe 8 body condition–related features. A manual BCS of each cow was independently assigned by 2 trained assessors using the same predefined protocol. With the extracted features as inputs and manual BCS as the reference, we built a nearest-neighbor classification model to classify BCS and obtained an overall classification sensitivity of 0.72 using a 10-fold cross-validation. We conclude that the sensitivity of automated BCS classification has been improved by expanding the selection of body condition–related features extracted from multiple body regions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Nova explosions are caused by global thermonuclear runaways triggered in the surface layers of accreting white dwarfs
. It has been predicted
that localized thermonuclear bursts on white dwarfs can ...also take place, similar to type-I X-ray bursts observed in accreting neutron stars. Unexplained rapid bursts from the binary system TV Columbae, in which mass is accreted onto a moderately strong magnetized white dwarf from a low-mass companion, have been observed on several occasions in the past 40 years
. During these bursts, the optical/ultraviolet luminosity increases by a factor of more than three in less than an hour and fades in around ten hours. Fast outflows have been observed in ultraviolet spectral lines
, with velocities of more than 3,500 kilometres per second, comparable to the escape velocity from the white dwarf surface. Here we report on optical bursts observed in TV Columbae and in two additional accreting systems, EI Ursae Majoris and ASASSN-19bh. The bursts have a total energy of approximately 10
times than those of classical nova explosions (micronovae) and bear a strong resemblance to type-I X-ray bursts
. We exclude accretion or stellar magnetic reconnection events as their origin and suggest thermonuclear runaway events in magnetically confined accretion columns as a viable explanation.
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IJS, KISLJ, NUK, SBMB, UL, UM, UPUK
The objectives of this study were to quantify the error of body weight prediction using automatically measured morphological traits in a 3-dimensional (3-D) vision system and to assess the influence ...of various sources of uncertainty on body weight prediction. In this case study, an image acquisition setup was created in a cow selection box equipped with a top-view 3-D camera. Morphological traits of hip height, hip width, and rump length were automatically extracted from the raw 3-D images taken of the rump area of dairy cows (n = 30). These traits combined with days in milk, age, and parity were used in multiple linear regression models to predict body weight. To find the best prediction model, an exhaustive feature selection algorithm was used to build intermediate models (n = 63). Each model was validated by leave-one-out cross-validation, giving the root mean square error and mean absolute percentage error. The model consisting of hip width (measurement variability of 0.006 m), days in milk, and parity was the best model, with the lowest errors of 41.2 kg of root mean square error and 5.2% mean absolute percentage error. Our integrated system, including the image acquisition setup, image analysis, and the best prediction model, predicted the body weights with a performance similar to that achieved using semi-automated or manual methods. Moreover, the variability of our simplified morphological trait measurement showed a negligible contribution to the uncertainty of body weight prediction. We suggest that dairy cow body weight prediction can be improved by incorporating more predictive morphological traits and by improving the prediction model structure.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Quantum computation requires quantum logic gates that use the interaction within pairs of quantum bits (qubits) to perform conditional operations. Superconducting qubits may offer an attractive route ...towards scalable quantum computing. In previous experiments on coupled superconducting qubits, conditional gate behaviour and entanglement were demonstrated. Here we demonstrate selective execution of the complete set of four different controlled-NOT (CNOT) quantum logic gates, by applying microwave pulses of appropriate frequency to a single pair of coupled flux qubits. All two-qubit computational basis states and their superpositions are used as input, while two independent single-shot SQUID detectors measure the output state, including qubit-qubit correlations. We determined the gate's truth table by directly measuring the state transfer amplitudes and by acquiring the relevant quantum phase shift using a Ramsey-like interference experiment. The four conditional gates result from the symmetry of the qubits in the pair: either qubit can assume the role of control or target, and the gate action can be conditioned on either the 0-state or the 1-state. These gates are now sufficiently characterized to be used in quantum algorithms, and together form an efficient set of versatile building blocks.
The introduction of programmed cell death protein 1 (PD-1) blockers (i.e. nivolumab and pembrolizumab) has significantly improved the prognosis of patients with advanced melanoma. However, the long ...treatment duration (i.e. two years or longer) has a high impact on patients and healthcare systems in terms of (severe) toxicity, health-related quality of life (HRQoL), resource use, and healthcare costs. While durable tumour responses have been observed and PD-1 blockade is discontinued on an individual basis, no consensus has been reached on the optimal treatment duration. The objective of the Safe Stop trial is to evaluate whether early discontinuation of first-line PD-1 blockade is safe in patients with advanced and metastatic melanoma who achieve a radiological response.
The Safe Stop trial is a nationwide, multicentre, prospective, single-arm, interventional study in the Netherlands. A total of 200 patients with advanced and metastatic cutaneous melanoma and a confirmed complete response (CR) or partial response (PR) according to response evaluation criteria in solid tumours (RECIST) v1.1 will be included to early discontinue first-line monotherapy with nivolumab or pembrolizumab. The primary objective is the rate of ongoing responses at 24 months after discontinuation of PD-1 blockade. Secondary objectives include best overall and duration of response, need and outcome of rechallenge with PD-1 blockade, and changes in (serious) adverse events and HRQoL. The impact of treatment discontinuation on healthcare resource use, productivity losses, and hours of informal care will also be assessed. Results will be compared to those from patients with CR or PR who completed 24 months of treatment with PD-1 blockade and had an ongoing response at treatment discontinuation. It is hypothesised that it is safe to early stop first-line nivolumab or pembrolizumab at confirmed tumour response while improving HRQoL and reducing costs.
From a patient, healthcare, and economic perspective, shorter treatment duration is preferred and overtreatment should be prevented. If early discontinuation of first-line PD-1 blockade appears to be safe, early discontinuation of PD-1 blockade may be implemented as the standard of care in a selected group of patients.
The Safe Stop trial has been registered in the Netherlands Trial Register (NTR), Trial NL7293 (old NTR ID: 7502), https://www.trialregister.nl/trial/7293 . Date of registration September 30, 2018.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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