Abstract
We introduce the Automatic Learning for the Rapid Classification of Events (ALeRCE) broker, an astronomical alert broker designed to provide a rapid and self-consistent classification of ...large etendue telescope alert streams, such as that provided by the Zwicky Transient Facility (ZTF) and, in the future, the Vera C. Rubin Observatory Legacy Survey of Space and Time (LSST). ALeRCE is a Chilean-led broker run by an interdisciplinary team of astronomers and engineers working to become intermediaries between survey and follow-up facilities. ALeRCE uses a pipeline that includes the real-time ingestion, aggregation, cross-matching, machine-learning (ML) classification, and visualization of the ZTF alert stream. We use two classifiers: a stamp-based classifier, designed for rapid classification, and a light curve–based classifier, which uses the multiband flux evolution to achieve a more refined classification. We describe in detail our pipeline, data products, tools, and services, which are made public for the community (see
https://alerce.science
). Since we began operating our real-time ML classification of the ZTF alert stream in early 2019, we have grown a large community of active users around the globe. We describe our results to date, including the real-time processing of 1.5 × 10
8
alerts, the stamp classification of 3.4 × 10
7
objects, the light-curve classification of 1.1 × 10
6
objects, the report of 6162 supernova candidates, and different experiments using LSST-like alert streams. Finally, we discuss the challenges ahead in going from a single stream of alerts such as ZTF to a multistream ecosystem dominated by LSST.
To assess efficacy (event-free survival, EFS) and safety in patients followed up for 3 years in the PrefHer study (NCT01401166).
Post surgery and post chemotherapy in the (neo)adjuvant setting, ...patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer were randomised to receive four cycles of the subcutaneous form of trastuzumab (Herceptin® SC H SC via single-use injection device Cohort 1 or delivery via a hand-held syringe from an SC Vial Cohort 2; 600 mg fixed dose) followed by four of the intravenous form of trastuzumab (Herceptin® H IV; 8 mg/kg loading, 6 mg/kg maintenance doses) in the adjuvant setting or vice versa every 3 weeks. Patients could have received H before randomisation. H was then continued to complete a total of 18 cycles, including any cycles received before randomisation.
A total of 488 patients were randomised across both cohorts. After median follow-up of 36.1 months, 3-year EFS across both groups in the evaluable intention-to-treat population (467 patients) was 90.6% overall, 89.9% in Cohort 1, and 91.1% in Cohort 2. No new safety signals were identified during long-term follow-up, with only one cardiac serious adverse event in the safety population (483 patients).
Three-year EFS data following H SC and H IV treatment are consistent with those reported by previous trials for H in the adjuvant setting. The overall safety profile during adjuvant treatment was as expected.
•3-year event-free survival data in PrefHer were consistent with previous trials.•The overall safety profile during adjuvant treatment was as expected.•H SC was well tolerated and no new safety signals were identified.
Clinical trial participants who benefit from experimental neural devices for the treatment of debilitating and otherwise treatment-resistant conditions are generally not ensured continued access to ...effective therapy or maintenance of devices at the conclusion of trials.
Objective/Hypothesis: Post-trial obligations have been extensively examined in the context of drug trials, but there has been little empirical examination of stakeholder perspectives regarding these obligations in the rapidly growing field of neural device research.
This study examined the perspectives of 44 stakeholders (i.e., 23 researchers and 21 patient-participants) involved in implantable neural device trials.
Researchers were concerned about current post-trial management, identified barriers like cost, and suggested ways to improve the system. Many patient-participants were unaware of whether they would have post-trial access, but most thought they should keep devices if beneficial, and agreed with researchers that more should be done to help them keep and maintain these neural devices.
To our knowledge, this is the first in-depth examination of researcher perspectives regarding continued access to experimental neural devices and only the second such examination of patient-participant perspectives. These data can help inform future ethical and policy decisions about post-trial access to implantable neurotechnology.
•Post-trial access to beneficial implantable neural devices is generally not ensured.•Lack of post-trial access is ethically problematic when participants do not have other alternatives.•Researchers were concerned about current post-trial management and identified barriers.•Many participants were unaware of whether they would have post-trial access, but most thought they should keep devices if beneficial.
Interest and investment in closed-loop or adaptive deep brain stimulation (aDBS) systems have quickly expanded due to this neurotechnology's potential to more safely and effectively treat refractory ...movement and psychiatric disorders compared to conventional DBS. A large neuroethics literature outlines potential ethical concerns about conventional DBS and aDBS systems. Few studies, however, have examined stakeholder perspectives about ethical issues in aDBS research and other next-generation DBS devices. To help fill this gap, we conducted semi-structured interviews with researchers involved in aDBS trials (
= 23) to gain insight into the most pressing ethical questions in aDBS research and any concerns about specific features of aDBS devices, including devices' ability to measure brain activity, automatically adjust stimulation, and store neural data. Using thematic content analysis, we identified 8 central themes in researcher responses. The need to measure and store neural data for aDBS raised concerns among researchers about
issues (noted by 91% of researchers), including the avoidance of unintended or unwanted third-party access to data. Researchers reflected on the
(83%) of aDBS due to the experimental nature of automatically modulating then observing stimulation effects outside a controlled clinical setting and in relation to need for surgical battery changes. Researchers also stressed the importance of ensuring
(74%). Concerns related to
(65%) were discussed, including current uncertainties about biomarker validity. Additionally, researchers discussed the potential impacts of automatic stimulation on patients'
(57%). Lastly, researchers discussed concerns related to
(defining criteria for candidacy) (39%), challenges of ensuring
(39%), and potential effects on
(30%). To help address researcher concerns, we discuss the need to minimize cybersecurity vulnerabilities, advance biomarker validity, promote the balance of device control between patients and clinicians, and enhance ongoing informed consent. The findings from this study will help inform policies that will maximize the benefits and minimize potential harms of aDBS and other next-generation DBS devices.
Persistent high-risk human papillomavirus (HR-HPV) infections play a major role in the development of invasive cervical cancer (CC), and screening for such infections is in many countries the primary ...method of detecting and preventing CC. HPV typing can be used for triage and risk stratification of women with atypical squamous cells of undetermined significance (ASC-US)/low-grade cervical lesions (LSIL), though the current clinical practice in Mexico is to diagnose CC or its preceding conditions mainly via histology and HR-HPV detection. Additional information regarding these HPV infections, such as viral load and co-infecting agents, might also be useful for diagnosing, predicting, and evaluating the possible consequences of the infection and of its prevention by vaccination. The goal of this follow-up hospital case study was to determine if HPV types, multiple HPV infections, and viral loads were associated with infection persistence and the cervical lesion grade. A total of 294 cervical cytology samples drawn from patients with gynecological alterations were used in this study. HPV types were identified by real-time PCR DNA analysis. A subset of HPV-positive patients was reevaluated to identify persistent infections. We identified HPV types 16, 18, and 39 as the most prevalent. One hundred five of the patients (59%) were infected with more than one type of HPV. The types of HPV associated with multiple HPV infections were 16, 18, and 39. In the follow-up samples, 38% of patients had not cleared the initially detected HPV infection, and these were considered persistent. We found here an association between multiple HPV infections and high viral loads with and infection persistence. Our findings suggest there are benefits in ascertaining viral load and multiple HPV infections status of HR-HPV infections for predicting the risk of persistence, a requirement for developing CC. These findings contribute to our understanding of HPV epidemiology and may allow screening programs to better assess the cancer-developing risks associated with individual HR-HPV infections.
► Use of low calorific fuels in current gas turbine and combined cycle technology. ► Combined cycle components updates proposed for these fuels. ► Updates selected according to their technical ...feasibility and economic viability. ► Assessment of the updates effects in the performance of the redesigned plants.
The utilisation of low-calorific syngas fuels in conventional gas turbines and gas and steam combined cycle equipments has been studied by the authors over the last years. In the present work, the effects of using different fuels of the referred type on the performance of a gas and steam combined cycle performance are assessed. The main bottle-necks found when trying to exploit the potential of the syngas fuels considered are also identified and some general rules with regard to the necessary modifications that need to be implemented in standard plants are provided.
In continuation to this research line, the present work analyses the challenges that using syngas fuels have on the major equipment of a conventional combined cycle designed for natural gas operation. First, the most relevant constraints imposed by the new fuels onto the conventional power plant are identified. This leads to setting up a list of the bottle-necks that prevent the plant from fully exploiting the potential of the new fuels employed. A list of the necessary modifications of the existing pieces of equipment, selected according to their technical feasibility and economic viability, is developed accordingly. These design updates are then assessed by means of a performance analysis of the redesigned plant. The full analysis is based on commercial and in-house computer codes.
The modifications proposed in this work can be regarded as general rules to redesign existing combined cycle power plants. The conclusions drawn from the paper permit to envisage the work that needs to be done if the present combined cycle plants are to be adapted to syngas fuels in a near future.
Display omitted
► An efficient method for the determination of sixteen pesticides in atmospheric samples. ► XAD-4 is an interesting support for collecting gas-phase pesticides, with similar ...performances than the conventional XAD-2. ► The ultrasonic extraction is cheaper, less aggressive and time-consuming with excellent analytical parameters. ► The method has been successfully tested by using high volume atmospheric simulation chamber and field campaigns.
A reliable multi-residue method for determining gaseous and particulate phase pesticides in atmospheric samples has been developed. This method, based on full scan gas chromatography–mass spectrometry (GC–MS), allowed the proper determination of sixteen relevant pesticides, in a wide range of concentrations and without the influence of interferences. The pesticides were benfluralin, bitertanol, buprofezin, chlorfenvinphos, chlorpyrifos, chlorpyrifos-methyl, ethalfluralin, fenthion, lindane, malathion, methidathion, propachlor, propanil, pyriproxifen, tebuconazol and trifluralin. Comparisons of two types of sampling filters (quartz and glass fibre) and four types of solid-phase cartridges (XAD-2, XAD-4, Florisil and Orbo-49P) showed that the most suitable supports were glass fibre filter for particulate pesticides and XAD-2 and XAD-4 cartridges for gaseous pesticides (>95% recovery). Evaluations of elution solvents for ultrasonic-assisted extraction demonstrated that isooctane is better than ethylacetate, dichloromethane, methanol or a mixture of acetone:hexane (1:1).
Recovery assays and the standard addition method were performed to validate the proposed methodology. Moreover, large simulator chamber experiments allowed the best study of the gas-particle partitioning of pesticides for testing the sampling efficiency for the validation of an analytical multiresidue method for pesticides in air. Satisfactory analytical parameters were obtained, with a repeatability of 5
±
1%, a reproducibility of 13
±
3% and detection limits of 0.05–0.18
pg
m
−3 for the particulate phase and 26–88
pg
m
−3 for the gaseous phase. Finally, the methodology was successfully applied to rural and agricultural samples in the Mediterranean area.
The expansion of research on deep brain stimulation (DBS) and adaptive DBS (aDBS) raises important neuroethics and policy questions related to data sharing. However, there has been little empirical ...research on the perspectives of experts developing these technologies. We conducted semi-structured, open-ended interviews with aDBS researchers regarding their data sharing practices and their perspectives on ethical and policy issues related to sharing. Researchers expressed support for and a commitment to sharing, with most saying that they were either sharing their data or would share in the future and that doing so was important for advancing the field. However, those who are sharing reported a variety of sharing partners, suggesting heterogeneity in sharing practices and lack of the broad sharing that would reflect principles of open science. Researchers described several concerns and barriers related to sharing, including privacy and confidentiality, the usability of shared data by others, ownership and control of data (including potential commercialization), and limited resources for sharing. They also suggested potential solutions to these challenges, including additional safeguards to address privacy issues, standardization and transparency in analysis to address issues of data usability, professional norms and heightened cooperation to address issues of ownership and control, and streamlining of data transmission to address resource limitations. Researchers also offered a range of views on the sensitivity of neural activity data (NAD) and data related to mental health in the context of sharing. These findings are an important input to deliberations by researchers, policymakers, neuroethicists, and other stakeholders as they navigate ethics and policy questions related to aDBS research.
We aimed to analyze prognostic factors for relapse in stage I seminoma managed by either active surveillance or adjuvant chemotherapy, and to describe the long-term patterns of recurrence in both ...groups.
From 1994 to 2008, 744 patients were included in three consecutive, prospective risk-adapted studies by the Spanish Germ Cell Cancer Group. Low-risk patients were managed by surveillance and high-risk patients were given two courses of adjuvant carboplatin. Relapses were treated mainly with chemotherapy. Patient age, tumor size, histological variant, pT staging, rete testis invasion, and preoperative serum BHCG levels were assessed for prediction of disease-free survival (DFS).
After a median follow-up of 80 months, 63 patients (11.1%) have relapsed: 51/396 (14.8%) on surveillance and 12/348 (3.2%) following adjuvant carboplatin. Actuarial overall 5-year DFS was 92.3% (88.3% for surveillance versus 96.8% for chemotherapy, P = 0.0001). Median time to relapse was 14 months. Most recurrences were located at retroperitoneum (86%), with a median tumor size of 26 mm. All patients were rendered disease-free with chemotherapy (92%), radiotherapy (5%), or surgery followed by chemotherapy (3%). A nomogram was developed from surveillance patients that includes two independent, predictive factors for relapse: rete testis invasion and tumor size (as a continuous variable).
Long-term follow-up confirms the risk-adapted approach as an effective option for patients with stage I seminoma. The pattern of relapses after adjuvant chemotherapy is similar to that observed following surveillance. A new nomogram for prediction of DFS among patients on surveillance is proposed. Rete testis invasion and tumor size should be taken into account when considering the administration of adjuvant carboplatin. Prospective validation is warranted.
A proposal for high efficiency hybrid systems based on molten carbonate fuel cells is presented in this paper. This proposal is based on adopting a closed cycle bottoming gas turbine using ...supercritical carbon dioxide as working fluid as opposed to open cycle hot air turbines typically used in this type of power generators.
First, both bottoming cycles are compared for the same operating conditions, showing that their performances do not differ as much as initially expected, even if the initial objective of reducing compression work is accomplished satisfactorily. In view of these results, a profound review of research and industrial literature is carried out in order to determine realistic specifications for the principal components of the bottoming systems. From this analysis, it is concluded that an appropriate set of specifications must be developed for each bottoming cycle as the performances of compressor, turbine and recuperator differ significantly from one working fluid to another. Thus, when the operating conditions are updated, the performances of the resulting systems show a remarkable advantage of carbon dioxide based systems over conventional air units. Actually, the proposed hybrid system shows its capability to achieve 60% net efficiency, what represents a 10% increase with respect to the reference system.
PDF
