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Background/Aims During the COVID-19 pandemic rheumatology services were advised to limit face to face contact, with remote telemedicine used instead. Although suitable for some people, issues have been highlighted with telemedicine. The frequency and proportion of remote appointments during the pandemic has not been described, or the socio-demographic characteristics of those accessing remote or in-person rheumatology care. This study aims to describe rheumatology healthcare utilisation and mode of appointment (remote/in-person) in people with rheumatoid arthritis (RA), prior to, and during the pandemic in England. Methods A retrospective prevalent cohort study of people with RA, identified using a validated algorithm, as of 1st April 2019 using electronic health record data (OpenSAFELY). Outpatient rheumatology appointments between 1st April 2019 and 31st March 2022 were identified. For each year, the number of outpatient appointments, mode of appointment (remote/in-person) and patient socio-demographic characteristics were described. Results 130,884 people with RA were identified. Since the start of the pandemic, the proportion of people without any appointments in a 12-month period increased from 28.5% in 2019/20 to 33.3% in 2020/ 21 and has not recovered. Older people were most frequently not seen (51% of people >80 years in 2020/21 and 2021/22). Of appointments where mode was known, 54.4% of people with appointments in the year from April 2020 were only seen remotely, reducing to 35.1% in the year from April 2021 (Table 1). The proportion with all remote appointments increased with increasing age, comprising 62% of people >80 years in 2020. This age gradient persisted in 2021, though proportions of those >80 years with all-remote appointments was lower (44%). Compared to urban dwellers, a higher proportion of those living in rural areas had all remote appointments in 2020 (58% vs 53%) and 2021 (38% vs 34%). Conclusion During the pandemic, one third of people with RA were not seen at all over a 12-month period and these were more frequently older people. Over half of people were only seen remotely in 2020, decreasing to one-third in 2021. Given the limitations of remote appointments it is unknown whether this increased frequency of remote appointments will impact long-term outcomes.
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Purpose: Drawing on the concept of community of practice, the purpose of this study was to explore Brazilian physical education teachers' experiences of nurturing a community of practice online during the COVID-19 pandemic. Method: This was an action research project, and the participants were 13 high school physical education teachers (one of them acted as teacher-facilitator), one critical friend, and one meta-critical friend. Data sources included teachers' online meetings, critical friend conversations, interviews, and the facilitator's reflexive journal. Results: Inductive analysis resulted in four themes: finding emotional and pedagogical support, building a teachers-only space, creating an online group dynamic, and negotiating to research their own practice. The findings are discussed in relation to the characteristics of community of practices and online continuing professional development. Conclusion: Key aspects for future online collaborative continuing professional development are highlighted: (a) teachers-only;(b) by teachers, for teachers;and (c) combination of tools.
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Objectives: In this study, we developed angiotensin-converting enzyme 2 (ACE2)-specific, peptide-derived 68Ga- and 18F-labeled radiotracers, motivated by the hypotheses that ACE2 is an important determinant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) susceptibility and that modulation of ACE2 in coronavirus disease 2019 (COVID-19) drives severe organ injury. Our current efforts are focusing on broader dissemination of ACE2-targeted PET radiotracers based on chelation of [18F]AlF enabling advanced murine and potentially human studies. Method(s): A series of NOTA-conjugated peptides derived from the known ACE2 inhibitor DX600 were synthesized, with variable linker identity. Since DX600 bears 2 cystine residues, both linear and cyclic peptides were studied. An ACE2 inhibition assay was used to identify lead compounds, which were labeled with 68Ga and 18F-AlF to generate the corresponding peptide radiotracers (68Ga-NOTA-PEP). The most potent 68Ga and 18F-AlF DX600 derivatives were subsequently studied in a humanized ACE2 (hACE2) transgenic model. Result(s): Cyclic DX-600-derived peptides had markedly lower half-maximal inhibitory concentrations than their linear counterparts. The 3 cyclic peptides with triglycine, aminocaproate, and polyethylene glycol linkers had calculated half-maximal inhibitory concentrations similar to or lower than the parent DX600 molecule. Peptides were readily labeled with 68Ga and 18F-AlF, and the biodistribution of both tracers was determined in an hACE2 transgenic murine cohort. Pharmacologic concentrations of coadministered NOTA-PEP (blocking) showed a significant reduction of 68Ga-NOTA-PEP4 signals in the heart, liver, lungs, and small intestine. Ex vivo hACE2 activity in these organs was confirmed as a correlate to in vivo results. The biodistribution of both tracers was similar, with apparent blocking observed in the lungs using the 18F-AlF peptide that needs to be verified via additional experiments. Conclusion(s): NOTA-conjugated cyclic peptides derived from the known ACE2 inhibitor DX600 retain their activity when N-conjugated for 68Ga or 18F-AlF chelation. In vivo studies in a transgenic hACE2 murine model using the lead tracer, 68Ga-NOTA-PEP4, showed specific binding in the heart, liver, lungs and intestine-organs known to be affected in SARS-CoV-2 infection. Blocking studies using the 18F-AlF labeled correlate showed modulation of PET signals in the normal lungs. These results suggest that 68Ga-NOTA-PEP4 or the 18F-AlF correlate could be used to detect organ-specific suppression of ACE2 in SARS-CoV-2-infected murine models and COVID-19 patients.Copyright © 2023 Southern Society for Clinical Investigation.
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BACKGROUND: Barriers to rapid return of sequencing results can affect the utility of sequence data for infection prevention and control decisions. AIM: To undertake a mixed-methods analysis to identify challenges that sites faced in achieving a rapid turnaround time (TAT) in the COVID-19 Genomics UK Hospital-Onset COVID-19 Infection (COG-UK HOCI) study. METHODS: For the quantitative analysis, timepoints relating to different stages of the sequencing process were extracted from both the COG-UK HOCI study dataset and surveys of study sites. Qualitative data relating to the barriers and facilitators to achieving rapid TATs were included from thematic analysis. FINDINGS: The overall TAT, from sample collection to receipt of sequence report by infection control teams, varied between sites (median 5.1 days, range 3.0-29.0 days). Most variation was seen between reporting of a positive COVID-19 polymerase chain reaction (PCR) result to sequence report generation (median 4.0 days, range 2.3-27.0 days). On deeper analysis, most of this variability was accounted for by differences in the delay between the COVID-19 PCR result and arrival of the sample at the sequencing laboratory (median 20.8 h, range 16.0-88.7 h). Qualitative analyses suggest that closer proximity of sequencing laboratories to diagnostic laboratories, increased staff flexibility and regular transport times facilitated a shorter TAT. CONCLUSION: Integration of pathogen sequencing into diagnostic laboratories may help to improve sequencing TAT to allow sequence data to be of tangible value to infection control practice. Adding a quality control step upstream to increase capacity further down the workflow may also optimize TAT if lower quality samples are removed at an earlier stage.
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BACKGROUND: In response to the COVID-19 pandemic, jurisdictions around the world implemented policies to reduce COVID-19 transmission through public masking, travel restrictions, and closure of non-essential businesses. Collectively known as non-pharmaceutical interventions (NPI), these strategies reliably reduce the spread of COVID-19. International data suggests NPI also reduce hospitalizations for pediatric respiratory infections and their consequences, particularly asthma exacerbation. However, few Canadian studies have examined the impact of NPI on hospitalizations for common causes of pediatric respiratory distress. OBJECTIVE(S): This study describes the impact of NPI on admissions for bronchiolitis, pneumonia, and asthma at a Canadian pediatric tertiary care centre. DESIGN/METHODS: A retrospective chart review was conducted including all pediatric patients <18 years admitted to the general pediatric and pediatric intensive care units with bronchiolitis, pneumonia, or asthma. Data regarding diagnosis, length of hospitalization, and mortality were collected before (September 2016-March 2020) and in the 6 months after provincial NPI implementation (March 2020-September 2020). NPI were present throughout this period, however, specific measures varied due to evolving public health orders. Chi-squared testing was conducted to describe the impact of NPI on number of admissions, length of hospitalization, and mortality. RESULT(S): Participants (n=1631) included 111 (6.8%) patients <1 month, 878 (53.8%) patients 1-23 months, 331 (20.3%) patients 24 months-4 years, and 311 (19.1%) patients >=5 years. A mean of 205 patients were admitted every 6 months with respiratory distress (bronchiolitis, pneumonia, and/or asthma) prior to NPI implementation. During this timeframe, the 6-month mean admissions due to asthma, pneumonia, and bronchiolitis were 48, 56, and 101, respectively. In the 6 months following NPI implementation, there were 56 admissions for respiratory distress, including 15 for asthma, 19 for pneumonia, and 22 for bronchiolitis. Mean length of stay increased following the implementation of NPI from 8.49 to 11.68 days, whereas 6-month mean mortality decreased from two to zero deaths. Results did not attain statistical significance (p>0.05). CONCLUSION(S): Results suggest NPI reduce hospitalizations and mortality from bronchiolitis, pneumonia, and asthma. Given the similar seasonality of these conditions, periodic use of NPI beyond the COVID-19 pandemic may reduce pediatric morbidity and mortality from common causes of respiratory distress. However, additional research is needed to describe the relationship between NPI and length of hospitalization. Future studies should also examine the impact of NPI on other pediatric infectious diseases to better characterize their utility.
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Background: Vaccine-induced Immune Thrombotic Thrombocytopenia (VITT) is a rare, anti-platelet factor 4 (PF4) antibody-mediated prothrombotic syndrome associated with the AstraZeneca (AZ) Covid-19 vaccination. Diagnostic criteria include thrombosis, thrombocytopenia, appropriate timing post AZ vaccine, and demonstration of an anti-PF4 antibody by enzyme-linked (Table Presented) immunosorbent assay (ELISA). ELISA methods have varying sensitivity and specificity for detecting anti-PF4 antibodies, therefore, functional assays (modified serotonin release and flow cytometry) assist in diagnosis. In Australia, the primary assay for detection of anti-PF4 antibodies is the Asserachrom HPIA IgG ELISA. Aim(s): To assess the accuracy of an alternate ELISA method for suspected VITT compared to the gold standard (clinicopathological diagnosis). Method(s): 96 stored frozen samples from patients with suspected VITT, previously analysed by Asserachrom HPIA IgG ELISA (Stago, Melbourne, Australia), were tested using the Hyphen Biomed Zymutest HIA IgG ELISA (Haematex Research, Sydney, Australia). These patients had confirmed thrombosis within 42 days post first dose of AZ vaccine. Cases were classified as 'serologically confirmed VITT' if clinicopathological criteria were met, and initial ELISA testing and/or functional assays were positive. Results were interpreted as positive or negative for anti-PF4 antibodies using the manufacturer's cut-offs derived for the diagnosis of Heparin-Induced Thrombocytopenia. Result(s): 96 patient samples were tested, including 35 classified as VITT (Table 1). The Hyphen assay had a moderate sensitivity (82%), including 2 probable false negatives on initial testing which were strongly positive by Hyphen assay. The specificity was 93%, including 5 probable false positives on initial ELISA which were negative by Hyphen assay (Table 2). Conclusion(s): The Hyphen ELISA is suitably accurate for the diagnosis of VITT. These data highlight the limitations of using a single ELISA testing method for anti-PF4 antibody detection. In cases with high clinical suspicion, a second ELISA method or functional assay should be considered.
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Case Diagnosis: 83-year-old male with spontaneous intracerebral hemorrhage (ICH) due to acquired Factor IX and XI clotting disorder from COVID-19 vaccine Case Description or Program Description: The patient was admitted with a spontaneous intracerebral hemorrhage managed conservatively before transfer to inpatient rehab facility. During his rehabilitation stay, he was found to have worsening left side weakness with concern for new spontaneous hemorrhage (ICH). Setting(s): Academic Inpatient Rehabilitation Facility and Academic Acute Care Hospital Assessment/Results: CT head showed expansion of the bleed in the right subinsular region and concern for new subfalcine and uncal herniation. Patient was transferred to the Neurosurgical ICU for further conservative management. Labs revealed an acute coagulopathy. Hematology was consulted and recommended mixing studies which did not correct, and Bethesda assay showing an acquired inhibitor of factor IX and XI. Malignancy workup and autoimmune titers were unremarkable. With unknown etiology, it was postulated that this may be vaccine related as patient received his last dose of the Moderna vaccine one month prior to admission and confirmed with positive COVID spike protein testing. Patient was placed on cyclophosphamide, rituximab, and high dose prednisone. He continued to have worsening weakness and dysphagia during his acute hospital admission and ultimately pursued comfort care. Discussion (relevance): Acquired hemophilia is a rare bleeding disorder due to production of inhibitors and against the body's own coagulation factors, which inhibits homeostasis. Deficiencies of factors IX and XI are very rare and typically caused by cancer or autoimmune disease. While very rare, acquired coagulopathy has been seen with the COVID-19 vaccine in only a handful of cases. Those reported have all been associated with Factor XIII. This is the first reported case, to our knowledge, of factor IX and XI inhibitor development after COVID vaccination. Conclusion(s): Acquired coagulopathy can occur after COVID-19 vaccine inducing a spontaneous hemorrhage and should be considered as part of the etiologies of ICH.
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Many consequences of climate change undermine the stability of global food systems, decreasing food security and diet quality, and exposing vulnerable populations to multiple forms of malnutrition. The emergence of pandemics such as Covid-19 exacerbate the situation and make interactions even more complex. Climate change impacts food systems at different levels, including changes in soil fertility and crop yield, composition, and bioavailability of nutrients in foods, pest resistance, and risk of malnutrition. Sustainable and resilient food systems, coupled with climate-smart agriculture, are needed to ensure sustainable diets that are adequately diverse, nutritious, and better aligned with contextual ecosystem functions and environmental conservation. Robust tools and indicators are urgently needed to measure the reciprocal food systems-climate change interaction, that is further complicated by pandemics, and how it impacts human health. Copyright © 2022 Owino, Kumwenda, Ekesa, Parker, Ewoldt, Roos, Lee and Tome.
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Background: We aimed to assess whether stress, boredom, drinking motives, and/or inhibitory control were related to alcohol use during a period of social isolation. Method: Analyses were carried out on questionnaire data (N = 337) collected during the first wave of the COVID-19 pandemic (7 April–3 May 2020). We first assessed changes in drinking behavior, stress and boredom. We then regressed drinking behavior on drinking motives, inhibitory control, stress, and boredom. We also investigated interactions between change in stress/boredom and inhibitory control. Results: A minority of respondents reported increased alcohol use (units = 23.52%, drinking days = 20.73%, heavy days = 7.06%), alcohol-related problems (9.67%), and stress (36.63%). Meanwhile, most respondents reported increased boredom (67.42%). Similarly, boredom significantly increased (B = 21.22, p <.001), on average, while alcohol-related problems decreased (B = −1.43 p <.001). Regarding drinking motives, decreased alcohol-related problems were associated with social drinking motives (B = −0.09, p =.005). Surprisingly, risk-taking was associated with decreased alcohol-related problems (B = −0.02, p =.008) and neither stress nor boredom independently predicted changes in alcohol use. Finally, several significant interactions suggested that those who were more impulsive and less bored were more likely to report increased alcohol use and vice versa. Conclusions: These data provide a nuanced overview of changes in drinking-related behavior during the COVID-19-induced period of social isolation. While most people reduced their drinking, there was evidence of complex interactions between impulsivity and boredom that may be explored in future studies. © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
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Human existence is complemented by environmental sounds as by-products of people's activities as well as intentionally generated sounds that allow human society to function, including transport and traffic sounds and notification sounds. The resulting soundscapes surround and permeate people's daily existence. Technological, as well as behavioural change causes some of these sounds to become extinct at the local or universal level. While expressions of human communication through spoken words (language) and song are deemed to be heritage and thus formally collected and documented, there is a general lack of consideration of the heritage potential of anthropogenic environmental sounds. Focussing on examples from the state of NSW (Australia), this paper discusses sound loss in the urban heritage environment and advances two variations of a conceptual framework to assist heritage practitioners in decision-making to assess heritage potential in order to safeguard some of these sounds for the future.
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The aviation sector represents an important terrain for contemporary environmental politics and policy. This position has been complicated by the Covid-19 pandemic, which led to a dramatic slowdown in international travel and threatened the position of the aviation and airline sectors. The temporality of this decline remains unclear. In this article, we present online qualitative research that explores how people think their flying habits might change in the future-in the wake of both Covid-19 and resultant social restrictions and awareness of climate breakdown. To do so, we foreground our analysis in Bristol, United Kingdom-a city characterized by a strong brand of green politics and debates surrounding airport expansion and the role of aviation in a net-zero future. This work adopted a research design conducted entirely online, incorporating surveys disseminated via local media and online focus groups. Findings from this work demonstrate that close to 60% of those surveyed will likely fly less in a post-Covid future. Furthermore, the Covid-19 pandemic has prompted a "reimagination" of flying-with important behavioral, policy, and justice implications. Our objective in presenting this work is twofold-first to illuminate emergent patterns of behavioral change in flying post-Covid and, second, to critically reflect on conducting online qualitative research in a pandemic. © 2022 by the Regents of the University of California. All rights reserved.
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The processing power of mobile devices including medical devices has increased substantially, so much so that devices that needed to connect to computers within the hospital for processing power now have significant amounts of processing power and memory on the own. The leverage of mobile, new technologies requires security that adapts to new scenarios. The invention of the Continuous Glucose Meter represents a breakthrough for diabetics, allowing them to manage their diet and insulin more precisely. A Clinical IoT trend, which has been accelerated by the COVID-19 Pandemic, has been the transition of acute care from the hospital to Long-Term Acute Care facilities and/or the home. In dealing with severely infectious patients, healthcare workers are at a significantly greater risk of infection than the overall population due to their frequency and time in contact with the infected patients. To resolve the issues of interconnectedness between healthcare components, businesses, government organizations worked to create standard methods for reducing paper-based healthcare records. © 2022 selection and editorial matter, Sherri Douville;individual chapters, the contributors.
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Introduction The CHaDOx1 nCov-19 AstraZeneca (AZ) vaccination has been associated with an antibody-mediated prothrombotic syndrome, termed “Thrombosis with Thrombocytopenia Syndrome” (TTS)[1-3]. The current diagnostic criteria for TTS are thrombosis (venous or arterial) within 4-42 days of AZ vaccine, thrombocytopenia and presence of an antibody to platelet factor 4 (PF4)[4, 5]. TTS commonly presents with cerebral venous sinus thrombosis (CVST) or splanchnic vessel thrombosis (SVT), but outside of TTS, CVST and SVT are uncommon, with an overall incidence of less than 0.5 per 100,000 [5-7]. Deep vein thrombosis (DVT) and pulmonary embolism (PE) are also associated with TTS, however the background incidence of venous thromboembolism (VTE) is much higher, with 1-2 events per 1000 patients per year[7, 8]. Therefore, many patients will present with new VTE and a recent exposure to the AZ vaccine, requiring consideration of investigation for TTS. Recent data suggests that PF4 antibodies can be seen in up to 8% of patients without thrombosis but following AZ vaccination[9]. We hypothesised in patients with recent AZ vaccination, new VTE but with a normal platelet count, that the incidence of a PF4 antibody is similar to this background rate of PF4 positivity. If confirmed, then presence of a normal platelet count despite new VTE and recent vaccination may exclude TTS without the need for PF4 antibody testing. We present our preliminary data on the rates of PF4 antibody positivity amongst patients with VTE, recent AZ vaccination and a normal platelet count at presentation. Aim and Methods To assess the incidence of PF4 ELISA positive results in patients with confirmed VTE, recent vaccination (within 4-42 days) with the first dose of AZ vaccine, and platelet count greater than 150x10 9/L. A retrospective audit of cases referred with suspected TTS to Monash Pathology, Melbourne, Victoria, and New South Wales Health Pathology at Royal Prince Alfred Hospital and St George Hospital sites Sydney, New South Wales, Australia, for testing for anti PF4 antibodies from 1 st April to 31 st July 2021. Patient sera were tested for the Anti-PF4 antibody using the STAGO Asserachrom HPIA IgG ELISA (Asnières sur Seine, France). For patients with a positive PF4 antibody test additional testing was sought for either the presence of platelet activating antibodies with a flow cytometry-based assay or the presence of spontaneous serotonin release without heparin in the serotonin release assay. Results From April 1 st to July 31 st 350 tests were run on 332 patients. 91 patients met our criteria, of whom 51 were female and 40 male, with a median age of 73 years. Median platelet count at presentation was 226x10 9/L, and median D dimer values were 10 times the upper limit of normal. 86 patients had either DVT, PE or both, including 2 with upper limb DVT, and 5 patients had PE with concurrent arterial events (1 axillary artery thrombosis, 3 arterial strokes, 1 coronary artery thrombosis). Further details are presented in table 1. 82 patient samples tested negative for anti-PF4 antibodies by ELISA, 5 were positive, and were 4 weak positive/equivocal (see table 2 for further details). Of the positive results, 3 had functional testing available, of which 2 were negative, and 1 showed discordant results, with a positive SRA but negative flow cytometry. None of the weak positive/equivocal cases had functional testing results available. Of the negative ELISA results, 5 patients had functional testing results available, of which 4 were negative. One of these cases had positive testing by flow cytometry, but negative by SRA (case included in table 2). Conclusion In our Australian cohort of patients with their first dose of AZ vaccine and new VTE within 4-42days, but a normal platelet count (therefore not fulfilling the clinical criteria of TTS), the incidence of a positive PF4 antibody test was 9/91 (9.9%, 95% CI 3.7-15.9%) and only one had evidence of platelet activating antibodies. This observed rate is similar to that observed in healthy patients wi hout thrombosis who received AZ vaccination as described by Thiele et. al., 2021. Further confirmation in a larger cohort of VTE patients is required, but if confirmed, then PF4 ELISA testing in patients with VTE and normal platelet count post AZ vaccine may not be required, and should give clinicians confidence to institute routine management. [Formula presented] Disclosures: No relevant conflicts of interest to declare.
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This paper details how a major international operator was able to work directly with a Managed Pressure Drilling (MPD) service provider during the global pandemic to mobilize to a deep water Tension Leg Platform (TLP) in the Gulf of Mexico in fewer than four weeks from notification to being operationally ready. Apart from the time crunch, the challenging part was achieving it virtually without face-to-face meetings or rig visit. The legacy hydraulically controlled MPD system used on the previous well had proven to be very challenging. It could not provide the desired precise control to maintain the annular pressures within the operational window, thus necessitating a change. Furthermore, the deck space limitations had significantly restricted the equipment that could be used to gain accurate pressure control. Despite COVID, all the planning stages were performed, albeit virtually, and a compact modular electric servo choke MPD system was deployed, installed, and commissioned within four weeks from the initial discussions. The new MPD system, which replaced the legacy system, was successfully utilized on this project executing the constant bottom hole pressure (CBHP) MPD variations. It achieved bottom hole pressure (BHP) control within a 0.1 - 0.2 ppg operational window. This paper will discuss how, operationally, this 1-man per shift MPD crew communicated with the rig and operator personnel, delivered accurate pressure control on connections, performed dynamic formation integrity tests (FITs), delivering flawless execution, and meeting the client's expectations. Global pandemic made big changes in our work, learning and interact with people with social distancing. © 2021, IADC/SPE Managed Pressure Drilling & Underbalanced Operations Conference & Exhibition
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Drilling the Point Pleasant-Utica formation in the Appalachian Basin has posed challenges to most operators, especially in Western Pennsylvania. A recent well drilled in this region demonstrated that with proper buy-in from the Operator, Constant Bottomhole Pressure (CBHP) Managed Pressure Drilling (MPD) could be the answer when planned and executed correctly. This paper drives the point that MPD is more than simply dropping chokes on location. Prior to drilling the well, the Operator initiated the communication very early with the MPD service provider and created an avenue to reduce the projected mud weight and develop a detailed CBHP MPD plan with a Pressurized Mudcap Drilling (PMCD) contingency. The anticipated challenges on this well were: High-pressure gas fractures, formation instability/shale breakout, severe/total loss of returns, inability to reach Target Depth, and casing/cementing issues. The Operator took time and worked with the new MPD service provider to carefully design and plan a new well (referred to as 'Y1' in this document), which helped execute the MPD part of the project within 30 days. In contrast, the MPD execution on a previous well (referred to as 'X2' in this document) with the older MPD service provider took more than 90 days. MPD execution on the new MPD well included dynamic influx management and loss mitigation, and understanding of the petro-physical conditions to reach the target. The significant factors that helped drill this well safely with a low Non-Productive Time (NPT) are excellent safety culture, communication, high quality and well-maintained MPD equipment, and a very knowledgeable and highly experienced MPD team. This project was finished within half of the budgeted Authorization for Expenditure (AFE), setting milestones in this region for this Operator. © 2021, IADC/SPE Managed Pressure Drilling & Underbalanced Operations Conference & Exhibition