Search

[Display omitted] Mepolizumab is an anti-IL-5 mAb treatment for severe eosinophilic asthma that reduces asthma exacerbations. Residual airway inflammation with mepolizumab therapy may lead to persistent exacerbations. Oral corticosteroids remain the main treatment for these residual exacerbations. Our study aimed to explore the corticosteroid responsiveness of airway inflammation after mepolizumab treatment to find potentially treatable inflammatory mechanisms beyond the IL-5 pathway. The MAPLE trial was a multicenter, randomized, double-blind, placebo-controlled, crossover study of 2 weeks of high-dose oral prednisolone treatment at stable state in 27 patients treated with mepolizumab for severe eosinophilic asthma. We analyzed paired sputum (n = 16) and plasma (n = 25) samples from the MAPLE trial using high-throughput Olink proteomics. We analyzed additional sputum proteins using ELISA. In patients receiving mepolizumab, prednisolone significantly downregulated sputum proteins related to type 2 inflammation and chemotaxis including IL-4, IL-5, IL-13, CCL24, CCL26, EDN, CCL17, CCL22, OX40 receptor, FCER2, and the ST2 receptor. Prednisolone also downregulated cell adhesion molecules, prostaglandin synthases, mast cell tryptases, MMP1, MMP12, and neuroimmune mediators. Neutrophilic pathways were upregulated. Type 2 proteins were also downregulated in plasma, combined with IL-12, IFN-γ, and IP-10. IL-10 and amphiregulin were upregulated. At stable state, prednisolone has broad anti-inflammatory effects on top of mepolizumab. These effects are heterogeneous and may be clinically relevant in residual exacerbations. [ABSTRACT FROM AUTHOR]

The experience of living with children with CP is dominated by the voice of the mother while others are rarely reported. Incorporation of the voices of other family members is important for a holistic understanding. Drawing on the philosophical perspectives of pragmatism, generic qualitative methodology, and Frank's narratives, this article highlights how restitution was constructed by 30 family members. They constructed restitution by hoping for a cure through either biomedical and/or alternative models of treatment, followed by intransitive and transcendent restitution. This appears to be the first time that restitution has been extended to families living with children with chronic illnesses. This would mean that paediatric nursing professionals and other health professionals dealing with family members living with children with CP could attend to their stories in an open and focused manner to honour and validate their stories as well as their experiences. [ABSTRACT FROM AUTHOR]

Understanding how asthma biomarkers relate to gene expression signatures could help identify drivers of pathogenesis. This post hoc exploratory analysis of the phase II tralokinumab trial MESOS (ClinicalTrials.gov identifier NCT02449473) aimed to profile baseline airway inflammation in patients with moderate-to-severe asthma. The T2 and T17 gene expression signatures, 3-gene mean and 5-gene mean, were calculated through transcriptomic analysis of baseline bronchial brushing samples. Clustering analysis using these signatures identified 3 distinct inflammatory subgroups: T2LOW/T17HIGH (n = 33), T2HIGH/T17LOW (n = 10), and T2LOW/T17LOW (n = 27). Fractional exhaled nitric oxide (F eno) levels were highest for T2HIGH/T17LOW and lowest for T2LOW/T17HIGH (median = 52.0 [range 42.5-116.3] and median = 18.8 [range 6.6-128.6] ppb, respectively; P =.003). High F eno levels were strongly correlated with high T2 gene expression (Spearman ρ = 0.5537; P <.001). Individual genes differentially expressed in patients with elevated levels of F eno , blood and bronchial submucosal eosinophil counts, and IgE level were explored, with cystatin SN (CST1) being the most upregulated gene in all subgroups (4.49- to 34.42-fold upregulation across clinically defined subgroups with high biomarker expression). F eno level may be useful to differentiate patients with T2 or T17 gene expression. Elevated F eno levels are associated with high CST1 expression. [ABSTRACT FROM AUTHOR]

• Manoomin (wild rice) is a sacred food and relative for Great Lakes American Indians. • University-tribal partnership transforms interdisciplinary research on manoomin. • Ten tenets for responsible university research with Indigenous peoples. • Collaborative research to support tribal sovereignty and environmental justice. Manoomin, the Ojibwe word for wild rice, grows in shallow lakes and streams and provides physical, spiritual, and cultural sustenance as a sacred food and relative for Indigenous peoples across the Great Lakes region of North America. Unfortunately, Manoomin has been declining due to multiple environmental stressors. In 2018, an interdisciplinary group from the University of Minnesota came together with natural resource managers from tribes and inter-tribal organizations to understand Manoomin within its socio-environmental context. This partnership grew despite a history fraught with settler colonial structures of knowledge production and commodification. Based on lessons learned from building this transformational partnership, this paper describes ten tenets for responsible research: 1) Honor Indigenous sovereignty and rights; 2) Address past and present harms; 3) Be on the path together with researchers and Indigenous partners; 4) Recognize, respect, and value Indigenous participation and intellectual labor; 5) Encourage the robust exchange of ideas; 6) Recognize that documents formalizing a relationship are not the whole relationship; 7) Make a plan for identifying and protecting sensitive Indigenous data; 8) Be prepared to navigate institutional obstacles; 9) Seek, support, and collaborate with diverse students; and 10) Actively listen and be open to different ways of engaging with the world. These lessons can serve as tools to form accountable partnerships that enable robust, nuanced, and effective environmental science, policy, and stewardship. [ABSTRACT FROM AUTHOR]

Electrochemical machining is a controlled metal shaping process based on anodic dissolution performed by the electrode reactions. When pulse signals, in the micro-second or less range, are combined with a small inter-electrode gap, the process is referred to as Micro-Electro-Chemical machining or μECM. The application of using nano-second/micro second pulses for μECM for certain passivation metals can be very limited by the formation of an oxide layer that prohibits the penetration of ultra-short pulse durations due to the capacitive effect of the oxide layer. This paper will present findings from the development of a μECM numerical model that incorporates an advanced hybrid time stepping approach for representing nano-second pulse interactions with the physical phenomena of the electrolytic environment associated with μECM, thereby enabling the characterisation of the capacitive model of the formed oxide barrier layer. Experimental work was conducted using nano and micro-second pulses on the machining of 18CrNi8 and copper using NaNO3 electrolyte. The μECM simulation model contributed to quantifying the lack of faradic machining of 18CrNi8 that was experimentally observed. A particular solution, believed to be effective in breaking through the oxide film, is to directly pre-polarize the layer by super imposing a DC signal prior to the ultra-short pulses, such that its capacity has been already loaded when the short pulse signal is applied. However, too long of a DC signal application time can lead to machining damage. Through the development of an ultra-short pulse simulation model, this work has established, that we can numerically determine an optimal DC signal duration necessary to load the oxide layer just enough for facilitating anodic dissolution during physical μECM process, thus minimising machining damage. [ABSTRACT FROM AUTHOR]

Study Objective: To evaluate practice patterns among gynecologic oncologists with regard to sentinel lymph node injection and biopsy in endometrial cancer.Design: An observational study with no control group.Setting and Patients: Active members of the Society of Gynecologic Oncology.Interventions: After institutional review board approval, we performed an online survey among active members of the Society of Gynecologic Oncology. Members were contacted via e-mail and their answers anonymously captured. Study data were collected using REDCap (REDCap developed by Vanderbilt University, Nashville TN).Measurements and Main Results: Three hundred eighteen of 1216 listed members completed the online survey. The majority of respondents (82.7%) perform sentinel lymph node sampling for endometrial cancer staging. Most technical aspects of sentinel lymph node sampling were consistently applied by the vast majority of respondents, including the choice of indocyanine green as a lymphatic tracer (97.3%) and its injection into the cervix (100%). Other technical aspects of sentinel lymph node sampling, such as the depth of injection, varied among respondents. Although 50.9% of the respondents perform an intraoperative assessment of the uterus by frozen section, only 17.9% assess sentinel lymph nodes by frozen section and/or touch prep. Some of the respondents' approaches are based on limited data, including (1) the use of sentinel lymph node injection and biopsy for high-risk histologies (performed by 69%-75% of the respondents dependent on the histology), (2) omitting side-specific completion lymphadenectomy in the absence of sentinel node mapping (in up to 57.8%), or (3) when lymph node metastases are present (in 39.9%).Conclusion: In summary, despite the growing use of sentinel lymph node injection and biopsy in endometrial cancer, practice patterns vary considerably among providers sampled by this survey. Some of the decisions are based on limited evidence and, in some instances, deviate from current published guidelines. [ABSTRACT FROM AUTHOR]

Objective This study aims to understand the treatment patterns and clinical outcomes of older women with cervical cancer compared to younger women. Methods Women undergoing care for cervical cancer between 2000 and 2013 at two academic institutions were identified. The cohort of older patients was defined as >65 years old at diagnosis. Patient charts were retrospectively reviewed, and clinical variables were extracted. Fisher's exact tests, logistic regression, and Kaplan-Meier analyses were performed. Results From 2000 to 2013 1119 women with cervical cancer were identified. Of these, 191 (17.0%) were >65 years old at the time of diagnosis. Older women were more likely to present with higher stage disease (p < 0.001). Controlling for stage, older women were less likely to undergo surgery during their treatment course (38% versus 70%, p < 0.001) and more likely to undergo radiation (77% versus 52%, p < 0.001), but no more likely to receive chemotherapy (p = 0.34). If they did undergo surgery, older women were less likely to have a pelvic lymph node dissection performed (41% versus 61%, p = 0.04), though the rate of positive pelvic lymph nodes was not different (p = 0.80). Overall survival was decreased in the older cohort (p < 0.001). A multivariate model identified age > 65 (HR 1.76, 95%CI 1.30–2.40), stage (HR 2.77, 95%CI 2.40–3.21), and ever undergoing surgery (HR 0.60, 95%CI 0.44–0.82) as independently associated with overall survival. Conclusions Women over age 65 with cervical cancer are less likely to undergo surgical management and were observed to have a decreased overall survival, even when controlling for use of surgery and stage of disease. [ABSTRACT FROM AUTHOR]

Despite increasing interest in learning from Indigenous communities, efforts to involve Indigenous knowledge in environmental policy-making are often fraught with contestations over knowledge, values, and interests. Using the co-production of knowledge and social order ( Jasanoff, 2004 ), this case study seeks to understand how some Indigenous communities are engaging in science-policy negotiations by linking traditional ecological knowledge (TEK), western science, and other knowledge systems. The analysis follows twenty years of Indigenous forest management negotiations between the Xáxli’p community and the Ministry of Forests in British Columbia (B.C.), Canada, which resulted in the Xáxli’p Community Forest (XCF). The XCF is an eco-cultural restoration initiative that established an exclusive forest tenure for Xáxli’p over the majority of their aboriginal territory—a political shift that was co-produced with new articulations of Xáxli’p knowledge. This research seeks to understand knowledge co-production with Indigenous communities, and suggests that existing knowledge integration concepts are insufficient to address ongoing challenges with power asymmetries and Indigenous knowledge. Rather, this work proposes interpreting XCF knowledge production strategies through the framework of “Indigenous articulations,” where Indigenous peoples self-determine representations of their identities and interests in a contemporary socio-political context. This work has broader implications for considering how Indigenous knowledge is shaping science-policy negotiations, and vice versa. [ABSTRACT FROM AUTHOR]

Study Objective: To assess outcomes of women with cervical cancer undergoing upfront radical hysterectomy (RH) via a minimally invasive surgery (MIS) or a traditional laparotomy (XL) approach at 2 large US academic institutions to determine whether the mode of surgery affects patient outcomes.Design: Retrospective cohort study (Canadian Task Force classification II-1).Setting: Two academic medical institutions in the United States.Patients: Women undergoing upfront RH for cervical cancer between 2000 and 2013.Intervention: Minimally invasive techniques (laparoscopic and robotic) for RH compared with XL.Measurements and Main Results: A total of 383 women met the eligibility requirements. Of these, 101 underwent an MIS (i.e., traditional laparoscopy, laparoendoscopic single site, or robotic) approach, and 282 underwent an XL approach. Overall survival (median not reached; p = .29) was not different between the 2 groups. Recurrence was rare and equivalent in the 2 groups, affecting 5.0% of patients in the MIS group and 6.4% of those in the XL group (p = .86). Pelvic lymph nodes were dissected in 98% of patients in the MIS group and 97% of those in the XL group (p > .99) and were found to be positive in 10.9% and 8.5% of those patients, respectively (p = .55). The mean number of pelvic lymph nodes retrieved was higher in the MIS group (19.4 vs 16.0; p < .001). There was no between-group difference in the rate of postoperative chemotherapy (p = .32) or radiation therapy (p = .28). Surgical margins were positive in 5.0% of specimens in the MIS group and in 4.6% of specimens in the XL group (p = .54). Although there was no difference in the overall rate of complications (15.1% and 17.2%, respectively; p = .87), laparotomy was associated with a higher median estimated blood loss (EBL) (50 cm3 vs 500 cm3) and a higher rate of perioperative blood transfusion (3.0% vs 26.2%; p < .001). Length of perioperative hospital stay was significantly shorter in the MIS group (1.9 days vs 4.9 days; p < .001).Conclusion: MIS RH does not compromise patient outcomes, including overall survival, rate of recurrence, and the frequency of pelvic lymph node dissection or positivity. Morbidity was decreased in the MIS group, including decreased EBL, fewer blood transfusions, and shorter hospital stay. [ABSTRACT FROM AUTHOR]

Electrochemical Machining (ECM) is a well-established process in areas such as the aviation and automobile industries but the further commercial development and use of the μECM process has been prohibited by several issues, the main one being the lack of a suitable power supply unit (PSU) that can deliver the high-current pulses required while maintaining a minimal form factor, physical geometry, and realistic cost. The work presented in the paper is based on research that was carried out during the development of a novel switch mode power supply (SMPS) that is capable of delivering nano-second pulses at the MHz frequency range to the machine tool with minimal inductance. Preliminary experimental work was conducted to obtain initial design parameters and specifications required for the power supply. This included analysis of load characterisation followed by an investigation into the power switching using gallium nitrate based field effect transistors (FETs) as a novel switching technology and an investigation of the effects of the Inter Electrode Gap (IEG) loop. A Pulse Width Modulator (PWM) Frequency generator was constructed that was tested and shown to produce a modulated frequency of up to 45 MHz with a minimum pulse on time of 14 ns. Methods were investigated and deployed for monitoring the current and voltage sensing feedback for optimising process performance and control. Control system requirements were defined and implemented by adapting a Texas Instrument Piccolo microcontroller specifically for interfacing with the PSU that was then integrated with the higher-level Delta Tau control system deployed for the controlling the overall machining process of the μECM demonstrator machine. The PSU was tested, validated and integrated with the demonstrator machine for a number of machining trials that were conducted on copper and 18CrNi8, with material removal observed. This paper will outline the development work that was undertaken for the PSU and present findings from the PSU control tests. In addition, findings will also be discussed and presented from the analysis of a novel multi-probe IEG connection concept which was shown to be correctly transmitting pulses to the IEG with a total loop inductance of just 50 nH with pulse-on times as short as 50 ns without any issue. [ABSTRACT FROM AUTHOR]

This paper presents an experimental investigation of Wire Electro Discharge Machining of Polycrystalline Diamond. The objective was to understand how the PCD reacts to the process parameters and to determine if there was a relationship between the parameters and surface finish and processing speed. Taguchi design of experiments was used to obtain the optimum conditions through the study of signal- noise (S/N) ratio for surface finish (Ra) and cutting speed (mm/s). ANOVA analysis was used to predict the significant machining parameters and develop a regression equation to model the machining process. Two L9 orthogonal arrays were developed in order to study the pulse generator parameters, (on-time, off-time, and servo voltage) and the physical parameters (wire tension, wire unspooling speed and injection pressure). A parallel experiment was performed using different coated wires. A total of six wires were tested (hard brass wire included), core materials such as Cu, CuZn36 and CuZn 63/37 and coating materials such as zinc diffused and zinc rich brass double layer were used. The results showed that coated wires will increase cutting speed to a value of 4.7 mm/min without affecting surface roughness drastically (0.8 μm Ra). Following the experimental analysis, successful results were achieved with an actual surface finish value of 0.68 μm Ra, which had an error of 12% compared with the predicted value. The highest cutting speed achieved was 4.8 mm/min, which was 8% less than the predicted value. [ABSTRACT FROM AUTHOR]

• Rhino-orbito-cerebral mucormycosis may be a co-infection derived from NeuroCOVID. • Use of corticosteroids in COVID-19 is associated with mucormycosis. • Cerebral mucormycosis may be a manifestation of post-COVID 19 neurological syndrome. [ABSTRACT FROM AUTHOR]

Solar-aided upgrade of the energy content of fossil fuels, such as natural gas, can provide a near-term transition path towards a future solar-fuel economy and reduce carbon dioxide emission from fossil fuel consumption. Both steam and dry reforming a methane-containing fuel stream have been studied with concentrated solar power as the energy input to drive the highly endothermic reactions but the concept has not been demonstrated at a commercial scale. Under a current project with the U.S. Department of Energy, PNNL is developing an integrated solar thermochemical reaction system that combines solar concentrators with micro- and meso-channel reactors and heat exchangers to accomplish more than 20% solar augment of methane higher heating value. The objective of our three-year project is to develop and prepare for commercialization such solar reforming system with a high enough efficiency to serve as the frontend of a conventional natural gas (or biogas) combined cycle power plant, producing power with a levelized cost of electricity less than 6¢/kWh, without subsidies, by the year 2020. In this paper, we present results from the first year of our project that demonstrated a solar-to-chemical energy conversion efficiency as high as 69% with a prototype reaction system. [ABSTRACT FROM AUTHOR]

A simple, sector specific webtool was developed within the EU funded ‘LCA to go’ project, to enable SMEs to perform first environmental assessments of their industrial machines and machine tools. The tool was applied together with several SMEs, sixteen of which provided feedback on their user experience, applicability, value of the results and future plans with the tool. The software flow of the webtool is presented together with a summary of the outcome of the case studies. Based on the feedback and the application of the webtool further development options for the sector specific tool were developed. [ABSTRACT FROM AUTHOR]

Abstract: Cervical Spondylotic Myelopathy (CSM) is the most common type of myelopathy in adults over 55 years of age. In the early stages symptoms may include local neck pain and stiffness that might mimic the presentation of non-specific mechanical neck pain (NSMNP). The patient was a 79 year old male, who complained of eight weeks of neck pain. He had been referred for physiotherapy by his family physician with a diagnosis of NSMNP. Initial presentation was consistent with the referral, but further assessment by the physiotherapist revealed findings suggestive of CSM. He was referred for an urgent cervical MRI scan, which revealed myelomalacic changes at C3/4 due to spondylotic changes. The patient was unsuitable for manual therapy intervention and was referred to a spinal orthopaedic surgeon who performed a posterior decompression and stabilisation at C3–C5, 2 months after the initial presentation. This case report highlights the importance of considering CSM in adults over 55 years of age presenting with NSMNP, particularly as the prevalence of both increases with age. It demonstrates the need for health professionals to carry out detailed examination where CSM may be a potential differential diagnosis. Outcomes are less favourable for patients over the age of 70, therefore an urgent surgical opinion was required for this patient. Deterioration of symptoms whilst he awaited surgery demonstrates how missed diagnosis may lead to possible long term spinal cord damage, with potential medico-legal concerns for the therapist. [Copyright &y& Elsevier]

Abstract: In this paper, we present the results of a Second Law analysis of a highly efficient, solar thermochemical reaction system for the production of syngas using micro- and meso-channel process technology. The evaluation includes the initial conversion of solar energy/exergy into physical energy/exergy and its subsequent conversion into chemical energy/exergy through the catalytic, endothermic reforming reaction, including quantifications of exergy destruction for components and the overall system. Possible applications include the combustion of the product syngas in a hybrid, solar/natural gas power plant, providing an efficient solar augment to the natural gas fuel; the thermochemical storage of solar energy, as part of an open or closed-cycle storage process; the production of hydrogen for use in fuel cells and for other purposes; and the production of synthetic fuels such as methanol or long-chain hydrocarbons. The analyses show that the overall process is exergetically-efficient and consistent with First Law and economic analyses. Finally, opportunities for improving the exergetic efficiency of the process are identified and discussed [Copyright &y& Elsevier]

Abstract: High quality holes of diameters less than 145 μm are required for the manufacture of next generation diesel fuel injection nozzles for improved combustion efficiency and reduction of emission to the environment. The current practice of using electro-discharge machining (EDM) drilling of fuel injection nozzles is limited in terms of the hole size it can produce effectively and the length of time needed to drill. In addition, the tooling cost is high. This paper reports on an investigation into a sequential laser and EDM micro-drilling technique for the manufacture of next generation fuel injection nozzles. A laser-drilled pilot hole is rimmed out by EDM drilling. It was found that this hybrid process has eliminated the problems of recast and heat affected zones typically associated with the laser drilling process. The new process has enabled a 70% reduction in total drilling time compared to standard EDM drilling as less material is removed by the EDM. The quality of the holes is as good as direct EDM drilling, thus eliminating the need for re-certification of the drilling process. Various combinations of laser/EDM drilling conditions have been examined. Optimum diameters for the pilot hole and the EDM electrode have been identified for a particular diameter of fuel injection nozzle, giving the minimum total drilling time and the best quality holes. A special system was designed to enable the alignment of nozzles to be controlled to within ± 20 μm. The technique has enabled valuable cost savings and increase in production capacity for next generation fuel injection nozzle manufacture. [Copyright &y& Elsevier]

Asymmetries are negatively associated with developmental precision. However, asymmetries in human traits, which consist partly or entirely of soft-tissue, are correlated with a surprising diversity of fitness domains, including fertility, disease resistance, running speed, aggression, and depression. We show that in men there are both between-subject differences in asymmetry and short-term (24 h) within-subject changes in soft-tissue asymmetry, and the latter are more pronounced in some subjects than in others. A number of hormones showed significant correlations with these changes, including positive associations between asymmetry and luteinising hormone (LH), total thyroxine (T4), and parathyroid hormone (PTH), and negative associations between asymmetry and follicle stimulating hormone (FSH). “Fixed” asymmetries accumulated during development represent long-term developmental imprecision and are related to various stressors. Nonfixed asymmetries in soft-tissue traits may correlate with short-term changes in hormone concentrations. We discuss the implications of our findings for the understanding of the relationships between asymmetry, behaviour, and fitness in men, and the possible patterns of short-term changes in asymmetry in male and female partners. [Copyright &y& Elsevier]

Background Exacerbations of asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous. Objective We sought to investigate the sputum cellular, mediator, and microbiome profiles of both asthma and COPD exacerbations. Methods Patients with severe asthma or moderate-to-severe COPD were recruited prospectively to a single center. Sputum mediators were available in 32 asthmatic patients and 73 patients with COPD assessed at exacerbation. Biologic clusters were determined by using factor and cluster analyses on a panel of sputum mediators. Patterns of clinical parameters, sputum mediators, and microbiome communities were assessed across the identified clusters. Results The asthmatic patients and patients with COPD had different clinical characteristics and inflammatory profiles but similar microbial ecology. Three exacerbation biologic clusters were identified. Cluster 1 was COPD predominant, with 27 patients with COPD and 7 asthmatic patients exhibiting increased blood and sputum neutrophil counts, proinflammatory mediators (IL-1β, IL-6, IL-6 receptor, TNF-α, TNF receptors 1 and 2, and vascular endothelial growth factor), and proportions of the bacterial phylum Proteobacteria. Cluster 2 had 10 asthmatic patients and 17 patients with COPD with increased blood and sputum eosinophil counts, type 2 mediators (IL-5, IL-13, CCL13, CCL17, and CCL26), and proportions of the bacterial phylum Bacteroidetes. Cluster 3 had 15 asthmatic patients and 29 patients with COPD with increased type 1 mediators (CXCL10, CXCL11, and IFN-γ) and proportions of the phyla Actinobacteria and Firmicutes. Conclusions A biologic clustering approach revealed 3 subgroups of asthma and COPD exacerbations, each with different percentages of patients with overlapping asthma and COPD. The sputum mediator and microbiome profiles were distinct between clusters. [ABSTRACT FROM AUTHOR]

CHRONOS''s purpose is to transform Earth history research by seamlessly integrating stratigraphic databases and tools into a virtual on-line stratigraphic record. In this paper, we describe the various components of CHRONOS''s distributed data system, including the encoding of semantic and descriptive data into a service-based architecture. We give examples of how we have integrated well-tested resources available from the open-source and geoinformatic communities, like the GeoSciML schema and the simple knowledge organization system (SKOS), into the services-oriented architecture to encode timescale and phylogenetic synonymy data. We also describe on-going efforts to use geospatially enhanced data syndication and informally including semantic information by embedding it directly into the XHTML Document Object Model (DOM). XHTML DOM allows machine-discoverable descriptive data such as licensing and citation information to be incorporated directly into data sets retrieved by users. [Copyright &y& Elsevier]