Breast cancer oncologists are challenged to personalize care with rapidly changing scientific evidence, drug approvals, and treatment guidelines. Artificial intelligence (AI) clinical ...decision-support systems (CDSSs) have the potential to help address this challenge. We report here the results of examining the level of agreement (concordance) between treatment recommendations made by the AI CDSS Watson for Oncology (WFO) and a multidisciplinary tumor board for breast cancer.
Treatment recommendations were provided for 638 breast cancers between 2014 and 2016 at the Manipal Comprehensive Cancer Center, Bengaluru, India. WFO provided treatment recommendations for the identical cases in 2016. A blinded second review was carried out by the center's tumor board in 2016 for all cases in which there was not agreement, to account for treatments and guidelines not available before 2016. Treatment recommendations were considered concordant if the tumor board recommendations were designated ‘recommended’ or ‘for consideration’ by WFO.
Treatment concordance between WFO and the multidisciplinary tumor board occurred in 93% of breast cancer cases. Subgroup analysis found that patients with stage I or IV disease were less likely to be concordant than patients with stage II or III disease. Increasing age was found to have a major impact on concordance. Concordance declined significantly (P ≤ 0.02; P < 0.001) in all age groups compared with patients <45 years of age, except for the age group 55–64 years. Receptor status was not found to affect concordance.
Treatment recommendations made by WFO and the tumor board were highly concordant for breast cancer cases examined. Breast cancer stage and patient age had significant influence on concordance, while receptor status alone did not. This study demonstrates that the AI clinical decision-support system WFO may be a helpful tool for breast cancer treatment decision making, especially at centers where expert breast cancer resources are limited.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Lightning is a dangerous yet poorly understood natural phenomenon. Lightning forms a network of plasma channels propagating away from the initiation point with both positively and negatively charged ...ends-called positive and negative leaders
. Negative leaders propagate in discrete steps, emitting copious radio pulses in the 30-300-megahertz frequency band
that can be remotely sensed and imaged with high spatial and temporal resolution
. Positive leaders propagate more continuously and thus emit very little high-frequency radiation
. Radio emission from positive leaders has nevertheless been mapped
, and exhibits a pattern that is different from that of negative leaders
. Furthermore, it has been inferred that positive leaders can become transiently disconnected from negative leaders
, which may lead to current pulses that both reconnect positive leaders to negative leaders
and cause multiple cloud-to-ground lightning events
. The disconnection process is thought to be due to negative differential resistance
, but this does not explain why the disconnections form primarily on positive leaders
, or why the current in cloud-to-ground lightning never goes to zero
. Indeed, it is still not understood how positive leaders emit radio-frequency radiation or why they behave differently from negative leaders. Here we report three-dimensional radio interferometric observations of lightning over the Netherlands with unprecedented spatiotemporal resolution. We find small plasma structures-which we call 'needles'-that are the dominant source of radio emission from the positive leaders. These structures appear to drain charge from the leader, and are probably the reason why positive leaders disconnect from negative ones, and why cloud-to-ground lightning connects to the ground multiple times.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Identification of risk factors and causes of stroke is key to optimize treatment and prevent recurrence. Up to one-third of young patients with stroke have a cryptogenic stroke according to current ...classification systems (Trial of ORG 10172 in Acute Stroke Treatment TOAST and atherosclerosis, small vessel disease, cardiac pathology, other causes, dissection ASCOD). The aim was to identify risk factors and leads for (new) causes of cryptogenic ischemic stroke in young adults, using the pediatric classification system from the IPSS study (International Pediatric Stroke Study).
This is a multicenter prospective cohort study conducted in 17 hospitals in the Netherlands, consisting of 1322 patients aged 18 to 49 years with first-ever, imaging confirmed, ischemic stroke between 2013 and 2021. The main outcome was distribution of risk factors according to IPSS classification in patients with cryptogenic and noncryptogenic stroke according to the TOAST and ASCOD classification.
The median age was 44.2 years, and 697 (52.7%) were men. Of these 1322 patients, 333 (25.2%) had a cryptogenic stroke according to the TOAST classification. Additional classification using the ASCOD criteria reduced the number patients with cryptogenic stroke from 333 to 260 (19.7%). When risk factors according to the IPSS were taken into account, the number of patients with no potential cause or risk factor for stroke reduced to 10 (0.8%).
Among young adults aged 18 to 49 years with a cryptogenic ischemic stroke according to the TOAST classification, risk factors for stroke are highly prevalent. Using a pediatric classification system provides new leads for the possible causes in cryptogenic stroke, and could potentially lead to more tailored treatment for young individuals with stroke.
Summary Background Pulsed high-dose dexamethasone induced long-lasting remission in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in a pilot study. The PREDICT study ...aimed to compare remission rates in patients with CIDP treated with high-dose dexamethasone with rates in patients treated with standard oral prednisolone. Methods In eight neuromuscular centres in the Netherlands and one in the UK, patients aged 18 years or older who had newly diagnosed definite or probable CIDP were randomly assigned to a treatment regimen of either pulsed high-dose dexamethasone or standard oral prednisolone. Randomisation was done with a random number generator. The primary outcome measure was remission at 12 months, defined as improvement of at least three points on the Rivermead mobility index and improvement of at least one point on the inflammatory neuropathy cause and treatment disability scale. Analysis was by intention to treat. This trial is registered with Current Controlled Trials, number ISRCTN07779236. Findings Between December, 2003, and December, 2008, 40 patients were treated: 24 received dexamethasone and 16 received prednisolone. At 12 months, 16 patients were in remission: ten in the dexamethasone group and six in the prednisolone group (odds ratio OR 1·2, 95% CI 0·3–4·4). Most adverse events were minor and did not differ substantially between treatment groups; however, sleeplessness and Cushing's face occurred more often in the prednisolone group. Interpretation Pulsed high-dose dexamethasone treatment did not induce remission more often than prednisolone treatment. A substantial proportion of patients were in remission at 12 months in both treatment groups. High-dose dexamethasone could be considered as induction therapy in CIDP, but comparison with intravenous immunoglobulin treatment is needed. Funding The Prinses Beatrix Fonds (MAR01-0213) and the Department of Neurology, Academic Medical Center.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Serotonergic function is known to fluctuate in association with light and temperature. Serotonin-related behaviors and disorders similarly vary with climatic exposure, but the associations are ...complex. This complexity may reflect the importance of dose and timing of exposure, as well as acclimation. This cross-sectional study tests how average climate exposures (ambient temperature and solar insolation) vary with the prevalence of a group of SSRI-treated disorders. For comparison, we similarly studied a group of disorders not treated by SSRIs (i.e substance use disorders). Psychiatric prevalence data were obtained from the Collaborative Psychiatric Epidemiology Surveys (CPES). Average yearly solar insolation was obtained from NASA's NLDAS-2 Forcing Dataset Information. Average yearly temperature was obtained from NOAA's US Climate Normals. Logistic regression models were generated to assess the relationship between these two climatic factors and the prevalence of SSRI-treated and substance use disorders. Age, gender, race, income, and education were included in the models to control for possible confounding. Temperature and insolation were significantly associated with the SSRI-responsive group. For an average 1 GJ/m2/year increase, OR was 0.90 (95% CI 0.85–0.96, p = 0.001), and for an average 10 °F increase, OR was 0.93 (95% CI 0.88–0.97, p = 0.001). This relationship was not seen with substance use disorders (insolation OR: 0.97, p = 0.682; temperature OR: 0.96, p = 0.481). These results warrant further investigation, but they support the hypothesis that chronic exposure to increased temperature and light positively impact serotonin function, and are associated with reduced prevalence of some psychiatric disorders. They also support further investigation of light and hyperthermia treatments.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Treatment results of AML in elderly patients are unsatisfactory. In an open label randomized phase II study, we investigated whether addition of the XPO1 inhibitor selinexor to intensive chemotherapy ...would improve outcome in this population. 102 AML patients > 65 years of age (median 69 (65–80)) were randomly assigned to standard chemotherapy (3 + 7) with or without oral selinexor 60 mg twice weekly (both arms n = 51), days 1–24. In the second cycle, cytarabine 1000 mg/m2 twice daily, days 1–6 with or without selinexor was given. CR/CRi rates were significantly higher in the control arm than in the investigational arm (80% (95% C.I. 69–91%) vs. 59% (45–72%; p = 0.018), respectively). At 18 months, event-free survival was 45% for the control arm versus 26% for the investigational arm (Cox-p = 0.012) and overall survival 58% vs. 33%, respectively (p = 0.009). AML and infectious complications accounted for an increased death rate in the investigational arm. Irrespective of treatment, MRD status after two cycles appeared to be correlated with survival. We conclude that the addition of selinexor to standard chemotherapy does negatively affect the therapeutic outcome of elderly AML patients. (Netherlands Trial Registry number NL5748 (NTR5902), www.trialregister.nl).
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Causes of stroke in young adults differ from those in the elderly individuals, and in a larger percentage, no cause can be determined. To gain more insight into the etiology of (cryptogenic) stroke ...in the young population, we investigated whether trigger factors, such as short-lasting exposure to toxins or infection, may play a role.
Patients aged 18-49 years with a first-ever ischemic stroke or intracerebral hemorrhage (ICH) in 17 participating centers in the Netherlands completed a questionnaire about exposure to 9 potential trigger factors in hazard periods and on a regular yearly basis. A case-crossover design was used to assess relative risks (RRs) with 95% confidence intervals (95% CIs) by the Mantel-Haenszel case-crossover method, for any stroke (ischemic stroke and ICH combined) and for different etiologic subgroups of ischemic stroke.
One thousand one hundred forty-six patients completed the questionnaire (1,043 patients with an ischemic stroke and 103 with an ICH, median age 44.0 years, 52.6% men). For any stroke, an increased risk emerged within 1 hour of cola consumption (RR 2.0, 95% CI 1.5-2.8) and vigorous physical exercise (RR 2.6, 95% CI 2.2-3.0), within 2 hours after sexual activity (RR 2.4, 95% CI 1.6-3.5), within 4 hours after illicit drug use (RR 2.8, 95% CI 1.7-4.9), and within 24 hours after fever or flu-like disease (RR 14.1, 95% CI 10.5-31.2; RR 13.9, 95% CI 8.9-21.9). Four trigger factors increased the risk of other determined and cryptogenic ischemic stroke, 3 that of cardioembolic stroke, 2 that of large vessel atherosclerosis and likely atherothrombotic stroke combined and stroke with multiple causes, and none that of stroke due to small vessel disease.
We identified cola consumption, vigorous physical exercise, sexual activity, illicit drug use, fever, and flu-like disease as potential trigger factors for stroke in the young population and found differences in the type and number of trigger factors associated with different etiologic subgroups of ischemic stroke. These findings might help in better understanding the pathophysiologic mechanisms of (cryptogenic) stroke in the young population.
Context.
Repeating fast radio bursts (FRBs) present excellent opportunities to identify FRB progenitors and host environments as well as to decipher the underlying emission mechanism. Detailed ...studies of repeating FRBs might also hold clues as to the origin of FRBs as a population.
Aims.
We aim to detect bursts from the first two repeating FRBs, FRB 121102 (R1) and FRB 180814.J0422+73 (R2), and to characterise their repeat statistics. We also want to significantly improve the sky localisation of R2 and identify its host galaxy.
Methods.
We used the Westerbork Synthesis Radio Telescope to conduct extensive follow-up of these two repeating FRBs. The new phased-array feed system, Apertif, allows one to cover the entire sky position uncertainty of R2 with fine spatial resolution in a single pointing. The data were searched for bursts around the known dispersion measures of the two sources. We characterise the energy distribution and the clustering of detected R1 bursts.
Results.
We detected 30 bursts from R1. The non-Poissonian nature is clearly evident from the burst arrival times, which is consistent with earlier claims. Our measurements indicate a dispersion measure (DM) of 563.5(2) pc cm
−3
, suggesting a significant increase in DM over the past few years. Assuming a constant position angle across the burst, we place an upper limit of 8% on the linear polarisation fraction for the brightest burst in our sample. We did not detect any bursts from R2.
Conclusions.
A single power-law might not fit the R1 burst energy distribution across the full energy range or widely separated detections. Our observations provide improved constraints on the clustering of R1 bursts. Our stringent upper limits on the linear polarisation fraction imply a significant depolarisation, either intrinsic to the emission mechanism or caused by the intervening medium at 1400 MHz, which is not observed at higher frequencies. The non-detection of any bursts from R2, despite nearly 300 h of observations, implies either a highly clustered nature of the bursts, a steep spectral index, or a combination of the two assuming that the source is still active. Another possibility is that R2 has turned off completely, either permanently or for an extended period of time.
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The LOFAR LBA Sky Survey de Gasperin, F.; Williams, W. L.; Best, P. ...
Astronomy and astrophysics (Berlin),
04/2021, Volume:
648
Journal Article
Peer reviewed
Open access
Context.
The LOw Frequency ARray (LOFAR) is the only radio telescope that is presently capable of high-sensitivity, high-resolution (i.e. < 1 mJy beam
−1
and < 15″) observations at ultra-low ...frequencies (< 100 MHz). To utilise these capabilities, the LOFAR Surveys Key Science Project is undertaking a large survey to cover the entire northern sky with Low Band Antenna (LBA) observations.
Aims.
The LOFAR LBA Sky Survey (LoLSS) aims to cover the entire northern sky with 3170 pointings in the frequency range between 42 − 66 MHz, at a resolution of 15″ and at a sensitivity of 1 mJy beam
−1
(1
σ
). In this work, we outline the survey strategy, the observational status, and the calibration techniques. We also briefly describe several of our scientific motivations and present the preliminary public data release.
Methods.
The preliminary images were produced using a fully automated pipeline aimed at correcting all direction-independent effects in the data. Whilst the direction-dependent effects, such as those from the ionosphere, have not yet been corrected, the images presented in this work are still ten times more sensitive than previous available surveys at these low frequencies.
Results.
The preliminary data release covers 740 deg
2
around the HETDEX spring field region at an angular resolution of 47″ with a median noise level of 5 mJy beam
−1
. The images and the catalogue of 25 247 sources have been publicly released. We demonstrate that the system is capable of reaching a root mean square (rms) noise of 1 mJy beam
−1
and an angular resolution of 15″ once direction-dependent effects are accounted for.
Conclusions.
LoLSS will provide the ultra-low-frequency information for hundreds of thousands of radio sources, providing critical spectral information and producing a unique data set that can be used for a wide range of science topics, such as the search for high redshift galaxies and quasars, the study of the magnetosphere of exoplanets, and the detection of the oldest populations of cosmic-rays in galaxies, clusters of galaxies, as well as those produced by active galactic nuclei.
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The Low-Frequency Array (LOFAR) Long-Baseline Calibrator Survey (LBCS) was conducted between 2014 and 2019 in order to obtain a set of suitable calibrators for the LOFAR array. In this paper, we ...present the complete survey, building on the preliminary analysis published in 2016 which covered approximately half the survey area. The final catalogue consists of 30 006 observations of 24 713 sources in the northern sky, selected for a combination of high low-frequency radio flux density and flat spectral index using existing surveys (WENSS, NVSS, VLSS, and MSSS). Approximately one calibrator per square degree, suitable for calibration of ≥200 km baselines is identified by the detection of compact flux density, for declinations north of 30° and away from the Galactic plane, with a considerably lower density south of this point due to relative difficulty in selecting flat-spectrum candidate sources in this area of the sky. The catalogue contains indicators of degree of correlated flux on baselines between the Dutch core and each of the international stations, involving a maximum baseline length of nearly 2000 km, for all of the observations. Use of the VLBA calibrator list, together with statistical arguments by comparison with flux densities from lower-resolution catalogues, allow us to establish a rough flux density scale for the LBCS observations, so that LBCS statistics can be used to estimate compact flux densities on scales between 300 mas and 2′′, for sources observed in the survey. The survey is used to estimate the phase coherence time of the ionosphere for the LOFAR international baselines, with median phase coherence times of about 2 min varying by a few tens of percent between theshortest and longest baselines. The LBCS can be used to assess the structures of point sources in lower-resolution surveys, with significant reductions in the degree of coherence in these sources on scales between 2′′ and 300 mas. The LBCS survey sources show a greater incidence of compact flux density in quasars than in radio galaxies, consistent with unified schemes of radio sources. Comparison with samples of sources from interplanetary scintillation (IPS) studies with the Murchison Widefield Array shows consistent patterns of detection of compact structure in sources observed both interferometrically with LOFAR and using IPS.
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