We assessed the collateral impact of the COVID−19 pandemic on healthcare service use among people with disabilities.We utilized the COVID−19 database from the Korean National Health Insurance Service claims from 2015 until June 2020. We included 5,850 people with disabilities and matched 5,850 without disabilities among those who were neither tested nor diagnosed with COVID−19. We used a quasi–experimental setting with a COVID−19 outbreak as an external event in a difference–difference estimation with matching controls.Participants with disabilities recorded a larger decrease in the number of claims for total services (2.1 claims per 5 months) upon the COVID−19 pandemic's onset compared to those without disabilities (1.6 claims), and the difference–in–difference estimates were statistically significant (0.46 claims). The decline was driven by outpatient and emergency visits. The extent of the decline was large for the severe disability group overall. By disability type, those with a physical disability showed a statistically significant decline in the number of claims.The COVID−19 pandemic has had a collateral impact on people with disabilities' use of healthcare services. Continued assessment is needed regarding whether the collateral impact has been sustained or is following a different path. The novel SARS–CoV−2 and the disease COVID−19 were first reported in late 2019, and the World Health Organization declared COVID−19 a global pandemic on March 11, 2020 . There wThe COVID−19 pandemic has caused collateral damage to the healthcare system in many countries; for example, the use of inpatient services fell by almost one–half after the onset of the pandemic in the United States, not only for elective surgeries but also for acute illnesses, such as stroke, cirrhosis, and myocardial infarction –8. The uConsiderable attention has been paid to the collateral influence of the COVID−19 pandemic on various non–COVID health outcomes, such as suicide , mortaliHealth disparities—defined as avoidable differences in health status or healthcare —between We analyzed data from the South Korean National Health Insurance Service (NHIS) COVID−19 database (DB), a retrospective cohort that includes all COVID−19 patients and their matched controls. The NHIS is the only public health insurer to have all Koreans as compulsory beneficiaries and every healthcare provider as a mandatory participant. The NHIS claims data include both enrollees' insurance qualification information and insurance claims from healthcare providers. Disability type and severity are included in the qualification information. In response to the COVID−19 pandemic, the Korean government publicly released the COVID−19 DB, which includes healthcare utilization data for 2020, covering medical claims from January 1, 2015, to July 31, 2020; this is the only publicly available dataset with healthcare use information from the COVID−19 pandemic period. The first diagnosis of COVID−19 in South Korea was made on January 8, 2020, so we considered 2020 as post–COVID−19 and all years up to 2019 as pre–COVID−19. Because the NHIS COVID−19 data were only compiled until July 2020, we used the 5–month data (from February to June) in each year from 2015 to 2020 for comparison.The NHIS COVID−19 DB includes patients who were diagnosed with COVID−19 from January 1 to June 4, 2020, those who were tested for COVID−19 but not diagnosed; and those who were randomly selected to match the COVID−19 patients using a ratio of 1:15, matching by sex, age, and residential region. This study excluded COVID−19 patients and those tested for COVID−19 infection, noting that these groups might differ from the general population. The Korean government released a National Code of Conduct in March 2020 and ordered a mandatory quarantine for all confirmed cases and their close contacts, with the former being secluded in designated public hospitals with no out–of–pocket expenses . Therefon = 121,050) and classified them as disabled  or nondisabled . We matched the disabled and non-disabled groups using a 1:1 ratio, employing a propensity score matching method with age group, gender, and Charlson comorbidity index (CCI) as matching variables. Age was measured in 10–year intervals ranging from 0–9 years to 80 years or older. The CCI is a widely used composite indicator for comorbidities ranging between 0  and 16 (the highest level of comorbidity) for 19 diseases, each of which is weighted from 1 to 6 by severity  framework to assess COVID−19's impact on healthcare service utilization by disability status. This DID framework allowed us to compare COVID−19's effects on the dependent variables for the treatment group (people with disabilities) and the control group (people without disabilities), respectively, by controlling background changes in outcomes that occur with time . We usedi and t indicate each participant and each year, respectively. Y represents a series of dependent variables: healthcare utilization  overall and by service type. If a specific service type was not used for a given observation, then the dependent variables were coded as zero. Disabled and Post are dummy variables denoting people with disabilities and the post–COVID−19 outbreak, respectively. Time is a linear variable that represents years, with 1 indicating the year 2015. X is a vector for the aforementioned confounding variables. ui is a constant error component for each participant.where 2+β3 represents marginal changes in Y after the COVID−19 outbreak among people with disabilities compared to pre–outbreak. β2 represents the marginal change in Y after the COVID−19 outbreak among people without disabilities compared to pre–outbreak. Therefore, β3 is the DID estimate for the incremental change of Y after the COVID−19 outbreak among people with disabilities when the difference in Y between pre– and post–outbreak among people without disabilities is controlled.βWe also estimated the DID after classifying disabilities as severe or mild as well as by disability type to assess variation in the COVID−19 outbreak's collateral impact by disability profile. All data extraction and statistical analyses were performed using SAS (version 9.4) and STATA (version 17).Dividing participants with disabilities into two groups by severity also uncovered an immediate decline in the number of claims at the beginning of the COVID−19 pandemic, with a larger decline for those with a mild disability compared to those with a severe disability. However, for emergency services, a sharper decrease was found among patients with severe disabilities than those with mild disabilities There were different healthcare service utilization outcomes by disability severity in terms of the number of claims. Participants with mild disabilities showed a decline in the number of claims for total and outpatient services  compared to the pre–COVID−19 period, controlling for the corresponding difference among those without disabilities. For emergency services, only participants with severe disabilities had a lower number of claims (by 0.0371 per 5 months per year) compared to the pre–COVID−19 period, controlling for the corresponding difference among those without disabilities  upon the onset of the pandemic, controlling for the pre–post difference among those without disabilities .The study revealed significantly larger decreases in healthcare service use overall and for outpatient and emergency services, particularly upon the onset of the COVID−19 outbreak among people with disabilities compared to those without disabilities. The study further showed that the severe disability group had a larger decline in medical expenditures compared to the mild disability group, with these declines being driven by emergency service use. The number of claims was estimated to decline for overall and outpatient services in the mild disability group but emergency services in the severe disability group.Although our findings do not account for the underlying mechanisms driving such differences, they at least highlight the need for continuous scrutiny. People with disabilities confront more challenges in situations such as the COVID−19 pandemic. For example, non-transparent masks hinder communication for people with hearing disabilities . HealthcWe estimated that the incremental decrease in the number of claims for overall healthcare services upon the onset of the COVID−19 pandemic was statistically significant among people with physical disabilities. There has been relatively few research on COVID−19's effect on people with disabilities (not to mention in terms of disability type) despite the significant attention paid to COVID−19's overall collateral impact . For exaWe acknowledge that this study has several limitations. First, some information is not present in insurance claims data because these data are originally collected administratively for reimbursement purposes. For example, in place of socioeconomic status, we were forced to substitute health insurance premium level, which is approximately proportionate to household incomes and assets, and qualification information for occupational status. We also note that the unit of analysis is claims per person rather than individual visits. Second, outpatient drug costs are not available in the COVID−19 DB. Third, we extracted the disabled and non-disabled groups from those who were neither tested for nor diagnosed with COVID−19 in the database. Nevertheless, this was the only database available in South Korea that included insurance claims during the COVID−19 outbreak.Despite some caveats, this study has several merits. A recent study in Korea estimated that people with disabilities had higher risks of major adverse outcomes from COVID−19, including admission to the intensive care unit, invasive ventilation, and mortality . HoweverGiven the data's limited availability, we assessed only the immediate impact of the COVID−19 outbreak on healthcare service utilization. Whether this short–term impact will be sustained or follow a different path should be assessed further after the additional accumulation of data. Additionally, long–term studies should use more specific service characteristics for assessment—including preventive healthcare or targeted services, such as rehabilitation or assistive care—to enable more purposeful responses to similar future shocks for people with disabilities. Future studies also need to assess whether there are variations in the collateral impact of the COVID−19 pandemic on people with disabilities by socioeconomic or demographic characteristics as well as other disability profiles such as disability duration or types uninvestigated in this study.Our findings have important implications for people with disabilities and the continuity of their care. People with disabilities used healthcare services  less frequently during the early stages of the COVID-19 pandemic relative to people without disabilities. Whether such declines stem from exacerbated access disparities during the COVID−19 outbreak and newly created disparities in health outcomes should be assessed in future work.https://nhiss.nhis.or.kr/bd/ab/bdaba000eng.do;jsessionid=EdTiA5aI1e1JP24bLXzVxDO7AasuZvIoWYvEa1306FNRmmHU75Yx2DamU4FI8L4U.primrose2_servlet_engine10.Publicly available datasets were analyzed in this study. This data can be found here: The studies involving human participants were reviewed and approved by Yonsei Institute Review Board (7001988– 202010–HR−1005–01E). Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.EH conceptualized the study, designed methodology, and prepared original draft. MS wrote original draft. HK curated data, wrote original draft preparation and contributed visualization of the results. HC and HyC reviewed and revised the manuscript. All authors contributed to the article and approved the submitted version.Funding was provided by the National Research Foundation of Korea (Grant no. 2022R1A2B5B0100125311) and the National Evidence–Based Healthcare Collaborating Agency (Grant no. HC20C0010).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The manual wheelchair skills training programme is used to structure teaching manual wheelchair use for people following injury or disability. This pilot study aimed to explore the outcomes of introducing a group wheelchair skills training programme on skill performance, confidence and frequency of wheelchair use for people with lower limb amputation in a rehabilitation setting from the perspective of participants and group facilitators.This pilot study used a two‐phase mixed methods nested design. Eleven people with lower limb amputations received a minimum of two 45‐min wheelchair skills sessions, using the Wheelchair Skills Training Program, delivered in a mix of group and one‐to‐one sessions. In phase one, wheelchair skill performance, confidence and frequency were measured using the Wheelchair Skills Test Questionnaire‐Version 5.0, goal achievement was measured through the Functional Independence Measure and Goal Attainment Scale. These measures were repeated in phase two. Nested within phase two was qualitative data collection. Interviews were conducted with eight participants and a focus group held with three programme facilitators, to gather their perceptions of the training process. Descriptive statistics were used to analyse and report quantitative data and thematic analysis was used to combine qualitative data from the two participant groups.Post intervention, the mean Wheelchair Skills Test Questionnaire score increased in performance (42.3 ± 13.4), confidence (33.9 ± 20.7) and frequency (33.9 ± 27.3). Goal Attainment was achieved or exceeded by 91% of all participants. Four themes were developed from qualitative data including, “motivators driving learning,” “delivery methods, structure and profile of the Wheelchair Skills Training Program,” “managing risk and safety” and “confidence in wheelchair use.”The pilot study found that The Wheelchair Skills Training Program can improve wheelchair performance, confidence and frequency to support enhanced safety, independence and quality of life for people with lower limb amputations. The first author has more than 5 years' experience in teaching wheelchair skills but all other facilitators had no prior experience. Facilitators were provided with written copies and links to the WSTP webpage. The day and the time of the WSTP remained flexible to accommodate participant availability. Over the three sessions, indoor skills were consolidated before progressing to community skills. In circumstances where only two sessions were completed, all indoor skills were covered, but sometimes there was insufficient time to fully address community skills. While the intent was to deliver WSTP in groups, this was not always possible with some one‐to‐one sessions occurring based on the availability of programme participants on the ward at the time of running the sessions. Participants who received individual training were able to have higher frequency of skill practice due to the facilitator only having one person to spot and all were encouraged to practice their skill acquisition in their own time if the occupational therapists agreed they were safe. The WSTP was completed using a manual wheelchair provided by the rehabilitation centre until participants sourced their own wheelchair.2.52.5.1Following provision of consent, electronic health records were used to collect demographic data regarding: sex, age, weight, diagnosis, other comorbidities, living/social situation and time since amputation.The first 21 of the 32 skills outlined in the Wheelchair Skills Test—Questionnaire (WST‐Q) (Version 5.0)  was used to measure achievement of occupation specific wheelchair goals through quantifying the meaning of goal achievement in specific and measurable terms. GAS is being increasingly used as an outcome measure in rehabilitative research  scores relating to mobility were captured to track wheelchair mobility changes pre and post WSTP , was excluded from the focus group. The focus group was completed on the ward by the second author (CM), an experienced researcher external to the programme. A flexible focus group guide, encompassing seven questions was developed by the second author (CM) and refined by the research team. Facilitators were asked about their experience of the WSTP, and any perceived benefits, challenges and recommendations see .2.6Descriptive statistics were used to analyse and report data from each domain of the WST‐Q , FIM and GAS into frequency distributions. Mean calculations with standard deviation were used to report data distribution and range . After the programme, they more often completed wheelchair skills when they needed or wanted to (mean percentage increase of 33.9 ± 27.3). Table 3.2.2Due to the varied functional abilities and comorbidities experienced by participants, goals identified by participants varied considerably in task demand (i.e. complex community access to simple self‐propelling at home). Ten participants experienced improvement in their GAS, achieving or exceeding their identified goal, with an average GAS change of two points ±1. An example of goal achievement included one participant moving from being pushed by a therapist within his home environment to being able to independently navigate his home with increased time and effort. One participant did not achieve their goal but did not decline in GAS score.3.2.3n = 9) recording a mobility FIM of six, meaning they could operate their wheelchair independently for a minimum of 50 m, turn around, manoeuvre the wheelchair to a table, bed and toilet, manoeuvre over rugs and over door sills and can negotiate a 3% graded ramp. The remaining two participants recorded a mobility FIM of five, indicating they could operate a wheelchair independently for short distances only, a minimum of 17 metres and there may be safety considerations or more time may be required to complete the task.Participants had an average mobility FIM change of 3.9 ± .5, with 82% (3.2.4n = 8) and facilitators (n = 3) are described using four themes including: motivators driving learning; delivery methods; structure and profile of the WSTP; managing risk and safety and confidence in wheelchair use.The collective perspectives of programme participants ((Evie‐facilitator).“We had a few issues from patients who did not want to come” (Chris‐participant)“Some people do not want to learn, want to sleep” There were conflicting opinions between participants and facilitators about the best way to learn wheelchair skills with participants not always being motivated.(Maxine‐facilitator)“you sort of pitch it that this is essential for your rehab and this is your main way of getting around and this is your mobility” According to facilitators, participants would engage sporadically and, on their terms, depending on who was in the group or their fatigue. Conflicting appointments and explanations of the programme influenced willingness to participate.(Maxine‐facilitator)“I feel like rapport is a big one. … as I developed my relationship with him, I could see that he realised that all the tips I am giving him actually makes his life easier.” Communication and rapport building were essential in maintaining engagement in the programme as well as knowing the participants' capacity well enough to set small realistic challenges and provide skill specific positive reinforcement.really (emphasis) patient driven.” (Robin‐facilitator)“You're kind of like helping them create goals, so I guess it is probably a little bit skewed in regards to being Participants not knowing whether they were a candidate for a prosthesis meant they were uncertain about what they wanted to achieve, leading to facilitators being over‐involved in their goal setting.(Robin‐facilitator)“I found it really easy to just come in and facilitate the session with the handout” Prior to the introduction of the WSTP, the training provided in wheelchair use was adhoc. Facilitators liked the structure of the WSTP and the manual to ensure that all key skills were covered.A large proportion of participants were ambivalent about the structure of sessions, including intensity and length. Freddie, Gerda and Edward found that the training grading and intensity were adequate and covered skills for a diverse age group, but Henry wanted more than one session a week to consolidate learning and Brad suggested sessions be longer to allow for the preservation of energy. One facilitator, Maxine, reflected that having three sessions provided flexibility to repeat and consolidate skills that participants found difficult. Maxine reported that session structure depended on the abilities of participants and their goals.(Chris‐participant)“I think family members must know about wheelchair. I know family help to make lunch or something else, but they do not know how to help transfer from wheelchair to other chair.” Participants additionally requested inclusion of wheelchair use during everyday tasks such as carrying objects when self‐propelling and suggested incorporating family members into training and provision of education around wheelchair maintenance.(Brad‐participant)“Seeing it done is way different to having someone say you have got to push here … it is a lot more instructional.” Visual learning tools were highly valued as participants had difficulty following verbal instructions, particularly with some of the advanced skills that were difficult to explain.Facilitators developed a strategy of asking participants to visualise their wheelchair wheel as a clock to assist with hand positioning and propulsion and they suggested learning could be further facilitated through watching videos of skills being performed (i.e. iPad) either prior to or during WSTP.(Robin‐facilitator)“I love it when patients encourage other patients. It is more effective than when the therapists encourage them, just because they have that bond … in it together.” (Freddie‐participant).“you can bounce off each other and sort of share‐ do it with someone else and yeah help each other through.” All facilitators and four participants agreed that there was value in the WSTP occurring in a group setting as well as one‐to‐one due to the peer support that was offered.slowing down and having a bit of a rest and thinking about that next move.” (Brad‐participant).Brad, who had both individual and group sessions found it advantageous that the group format allowed for “(Dave‐participant)“One‐to‐one is more focused, can be at the speed you are doing things” Facilitators reflected that it was rare to get concurrent eligible people with similar skill levels meaning they needed to be highly familiar with the process and participants. They suggested that low admissions during the time of the project exacerbated this issue. Some participants and facilitators wondered if one‐to one sessions were more advantageous because they could account for individual need.(Evie‐facilitator)“One time he actually did hit it (kerb) and almost went straight forward out of the wheelchair and … I was there to help prevent it from happening.” Sound clinical reasoning skills and proactive planning and close positioning during training supported facilitators to manage risk during the WSTP.An example of clinical reasoning included weighing up the risk of making the chair more tippy by moving forward rear axle settings to decrease stress placed on shoulders to enhance propulsion technique.(Robin‐facilitator)“Putting them in a situation where they are a little at risk, but with your support … then they have their own realisation that, no I should not be doing that” (Maxine‐facilitator)“Sometimes even though I wanted him to say he would not attempt something by himself, he would do it and so we'd do it together and then after he'd go OK actually that was really scary, I should not have done that.” Staff agreed that some level of risk helped participants learn more about their own ability to negotiate certain environments.There were some conflicting opinions amongst the facilitators about confidence to deliver the WSTP. Robin reported feeling confident through drawing on knowledge learnt at university, observing colleagues and through referring to the adapted WSTP checklist. However, Evie felt that it was challenging to teach skills that she was only learning herself.(Freddie‐participant)“It's given me a bit of confidence to use it [wheelchair] wherever I am, you have got to know what you are doing up and down places and I do not want to flip sideways” The WSTP was an opportunity to further assess the functional and cognitive performances of participants and link that back to decision making to facilitate discharge planning. Facilitators observed that participants who went through the WSTP were better equipped and more confident on discharge and this was affirmed by some participants.(Chris‐participant).“I am scared …. Can I hurt someone maybe?” (Brad‐participant)“Maybe I was too inexperienced with the wheelchair to be able to cope with the run offs and the footpaths …. I found it very scary.” Two participants, Brad and Chris, spoke about feeling “scared” and anxious about using a wheelchair, particularly within a community setting, where it was perceived there was a higher potential risk of injury to themselves and others.(Robin‐facilitator)“I guess in a more functional type setting that might be really handy. It goes hand in hand with OT [occupational therapy] does not it?” Both facilitators and participants saw the value in graded skill acquisition to build confidence. Facilitators suggested training in more advanced skills such as negotiating shopping centres was warranted to further support confidence and reinforce basic skills as well.4Findings of this research concur with earlier studies that suggest the WSTP builds wheelchair skill performance and confidence amongst wheelchair users (Keeler et al., Engagement in the WSTP was affected by challenges due to competing commitments and priorities, such as other rehabilitation or rest. It is unclear whether motivation played a role, or if the considerable impairment associated with a lower limb amputation and the process of coming to terms with the loss, may have interfered with their readiness to engage in rehabilitation and their willingness to engage in rich dialogue during interviews (Horgan & MacLachlan, Implementation of this programme onto a busy rehabilitation ward was also challenging due to the high levels of staff rotations, limited staffing availability and competing time demands. Staff reported low facilitation confidence, indicating that the expectation of learning risk management processes and experiential skill development on the job is a flawed approach and that alternate mechanisms may be more efficacious.A boot camp type approach that encompasses instruction, demonstration and hands on practice was identified as a successful method for learning the WSTP within Universities in North America (Giesbrecht, Wilson, et al., While it was recognised that group education enabled modelling and the provision of encouragement from others to support confidence, group education was challenging within the inpatient rehabilitation setting (Best et al., 4.1As this was a pilot study with a low sample size, the intent was not to produce generalisable results. Participants in the WSTP were also receiving usual rehabilitation and experiencing natural recovery of function meaning improvements in WST‐Q and GAS cannot be attributed solely to the WSTP. Only 31% of WSTP sessions were completed in a group setting as anticipated, meaning participants received differing levels of attention and time spent practising wheelchair skills. The first author, who was involved in goal setting, the delivery of the programme and collection of data was not blinded which may have introduced some bias as well as affecting honesty from participants when interviewed. Additionally, there was no follow‐up once participants left rehabilitation to see carryover of skills learned in the home environment.4.2This research highlights the importance of a structured programme for teaching wheelchair skills for people with amputations and some of the associated systematic challenges. Facilitators require training in the delivery of wheelchair skills to support their confidence, but this training needs to be flexible to reduce the amount of time spent away from clinical practice. Raising the profile of WSTP as ‘usual practice’ and developing systematic protocols and processes related to the WSTP within inpatient rehabilitation settings is recommended and important for safety.To support engagement with wheelchair skills training, it needs to be relevant to participants and this may be achieved through having a stronger occupational focus. The education and practising of more advanced wheelchair skills may be appropriate for completion within a community setting, where there may be stronger intrinsic motivation due to their environment (Siegert & Taylor, Structured education in wheelchair use builds skill capacity and confidence in people with amputations.An occupational focus may enhance wheelchair skills training.Occupational Therapists require flexible options for learning facilitation skills of WSTPThe authors have no conflict of interest to declare.KC conceptualised and designed the research with support from other authors. KC and CM collected the data. Data analysis was led by KC with all authors contributing. All authors contributed to framing the write up of the manuscript and reviewed the final drafts. KC wrote the first full draft of the manuscript with CM contributing editing and revisions.Data S1 Supporting InformationClick here for additional data file.


P = .03; 92% selection). Patients with AML report improved QoL after treatment, despite higher mean out‐of‐pocket expenditures compared with MDS , greater loss of productivity‐related income , and greater caregiver effects . Our results suggest that including patient‐reported QoL and socioeconomic indicators can improve the accuracy of survival models.Understanding how patient‐reported quality of life (QoL) and socioeconomic status (SES) relate to survival of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) may improve prognostic information sharing. This study explores associations among QoL, SES, and survival through administration of the Euro‐QoL 5‐Dimension, 3‐level and Functional Assessment of Cancer Therapy‐Leukemia and financial impact questionnaires to 138 adult participants with newly diagnosed AML or MDS in a longitudinal, pan‐Canadian study. Cox regression and lasso variable selection models were used to explore associations among QoL, SES, and established predictors of survival. Secondary outcomes were changes in QoL, performance of the QoL instruments, and lost income. We found that higher QoL and SES were positively associated with survival. The Lasso model selected the visual analog scale of the EQ‐5D‐3L as the most important predictor among all other variables ( Incidence rates nearly triple for those 70 and older and survival outcomes are poorer with increased age . DecisioThere is a growing literature that suggests patient‐reported outcomes, such as QoL, may improve the accuracy of risk models used to predict survival outcomes. Incorporating patient‐reported fatigue, for example, into the International Prognostic Scoring System for MDS (IPSS) has improved survival prediction . The proMissing or invisible prognostic data—such as patient‐reported QoL—may be a source of error in evaluating chances of successful treatment if it is impactful. There is reason to believe that QoL both impacts survival and is a measurable outcome for treatment. Long‐term AML survivors have reported poorer QoL compared to age‐matched members of the population without exposure to the disease or treatment . The abiSocioeconomic indicators are another unexplored and potentially impactfulmissing data. Studies in the Swedish population, have shown that elderly patients with geographic access to intensive treatment for AML live longer than those without . If riskKnowledge on the contribution that patient‐reported outcomes and/or SES has on survival and the resulting datasets generated could lead to improved modeling and better communication between clinicians and to patients and their families. In this study, we aim to explore the potential of these data to improve the accuracy of survival modeling and our understanding of how QoL and socioeconomic indicators change following treatment for AML and MDS. The study was part of the Terry Fox Research Institute's Prognostic Risk study for AML and MDS (NCT01685619), undertaken at six study centers across Canada.22.1Adults (age > 19) with a suspected diagnosis of AML or MDS were invited to join the observational, prognostic risk study, at six major cancer centers across Canada. The study was designed to collect biological, clinical, and patient‐reported outcomes data from newly diagnosed patients with AML or MDS. The overall study objective was to explore prognostic indicators related to remission and survival including genomic and molecular indicators under investigation by the laboratory‐based investigators, and clinical outcomes such as survival, QoL, health status, and personal financial impacts for patients with AML or MDS, over 24 months of follow‐up. Patients were considered for enrollment in part two of the study if a diagnosis of AML or MDS was confirmed from a bone marrow biopsy and patients re‐consented to the study. Demographic characteristics were obtained at baseline and changes to QoL and personal financial impacts were assessed over five follow‐up time points: baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3), 18 months (T4), and 24 months (T5). Recruitment started in October 2013 and ceased in March 2015 due to discontinuation in the funding for the laboratory‐based objectives, whereas funding for the clinical objectives was retained to complete follow‐up for participants who had enrolled prior to this date.2.2FLT3 and NPM1 for intermediate‐risk AML, and ckit for low‐risk AML. Molecular testing was only undertaken if individuals were candidates for induction/CR1 consolidation treatment, that is, without significant age or comorbidities to preclude treatment with alloSCT. If molecular testing results for FLT3 or NPM1 for intermediate risk or ckit mutations for core binding factor t or inv[16] AML were unavailable, an unconfirmed risk group status was assigned and included in the regression analysis as a dummy variable. All MDS‐related cytogenetic changes according to the WHO 2008 classification scheme were considered to be adverse‐risk AML.Cytogenetic risk for AML was assigned according to current NCCN guidelines , with th2.3Following REB approval at each of the six study centers, study coordinators trained in administering the questionnaires conducted interviews in person or over the telephone, at each of the time points. The questionnaires were translated into Canadian‐French for participants in the province of Quebec. Sociodemographic characteristics, treatments, outcomes, and reasons for missing data were reported on case report forms at each of the subsequent time points and returned to a central database. The questionnaire package included the Euro‐QoL 5‐Dimension, 3‐Level (EQ‐5D‐3L) to measure QoL according to preference‐weighted health utility and Functional Assessment of Cancer Therapy‐Leukemia (FACT‐LEU) and personal financial impact questionnaires. Clinicians provided subjective measures of health status at each time point with measures of Karnofsky Performance Scores along with hospital days, survival, and remission status. Results from the EQ‐5D‐3L were scored according to preference weights specific for Canada, to generate Canadian preference‐based index utility values . Individ2.4The validity of the EQ‐5D‐3L and FACT‐LEU was assessed for all participants, at each time point, through intra‐instrument item correlations and inter‐instrument total score correlations. The reliability of the FACT‐LEU was evaluated with the coefficient for Cronbach's alpha and the corrected item total correlation scores for both instruments were calculated, at each time point. Correlation with EQ‐5D‐3L index scores and the visual analogue scale (VAS) measured the relationship of the index score to an individual's own perception of QoL.2.5P‐values below .15 in a univariable analysis were included in the Cox regression and excluded by backward selection if their exclusion improved the Akaike information criteria score for the model. The coding of the variables and their selection for inclusion in the model were further refined to minimize any collinearity in the models. A complete list of all of the variables tested individually may be found in the Supporting Information. The proportional hazards assumption was tested in all models and a decision was made to adjust, stratify the model, or separately model effects for any variables that showed time‐dependent characteristics.Overall survival was defined as the time from enrollment in the study to either death or 24 months of follow‐up, whichever occurred first. Event rates were the ratio for the number of events to the person years at risk for the event. The median overall survival of the cohort was estimated using Kaplan Meir life tables and log rank equality of survivor functions. Variables from established prognostic risk models  were included a priori. All other study variables with P‐values for the Lasso model [We used the least absolute shrinkage and selection operator (Lasso) method to enhance the accuracy and interpretation of the results from the Cox model . The Lasso model . A boots2.6Multistate modeling was applied to the cohort data to simultaneously analyze QoL and survival outcomes. The method involves defining a set of health states that the cohort may experience and calculating the probability of transitions between them . We distFor each health state identified, the mean EQ‐5D‐3L index and FACT‐LEU scores were calculated. Any missing QoL data were accounted for by imputing missing values on health states with at least 60% of the complete data. Use of an imputed dataset is critical to analyses of patient‐reported outcomes in this disease area to adequately represent missing date due to adverse health status. The reason for missing data was recorded on the case report form and analyzed for each participant and time point. If the reason was related to poor health status , the imputed data were generated from the mean of the lowest quintile of the complete dataset, for each time point (T0‐T5). If the cause for the missing data was random, an imputation model was developed for each time point, using baseline and time‐dependent covariates to generate the missing values (see Supporting Information).2.7Mann‐Whitney rank sum tests were used to test mean differences in out‐of‐pocket expenditures and productivity income losses due to time off from paid work and QoL differences related to the health states modeled for this cohort. We used Chi‐squared or Fishers exact tests to distinguish frequencies of catastrophic healthcare spending, adverse impacts on caregiver productivity, and characteristics of nonresponding participants.3P = .03; 92% successful selection) . Of these, 51 individuals survived the 24‐month duration of follow‐up; 32 of the long‐term survivors had AML and 19 had MDS , suggesting good convergent validity between the two QoL instruments. Correlation of the EQ‐5D‐3L index score with the VAS, however, indicated the instrument had poor construct validity  across all time points. The corrected item total correlations (CITC) indicated only fair reliability for both instruments, with some CITC scores falling below the commonly referenced thresholds for reliability of 0.2; specifically, the CITC score for the anxiety and depression item on the EQ‐5D‐3L at month 6 was 0.16 and the social and family well‐being subscale of the FACT‐LEU at baseline was 0.17.P < .05). AML patients who had remissions longer than 6 months and those with MDS were more likely to respond with scores of perfect health, indicating a ceiling effect for the instrument and potential aggreability bias for people with more desirable outcomes.The multistate modeling defined 10 finite health states for this cohort Figure . Mean QoP = .05) and high medical costs may persist over longer terms of follow‐up; month six mean out‐of‐pocket expenses were $334 versus $129, P = .06. Nearly two thirds (67%) of all study participants reported out‐of‐pocket medical expenses that totaled more than 5% of their monthly income. Patients with AML who were in remission also reported greater productivity income losses at both T1 and T2 time points compared to all other patients. At T1 (3 months), patients with AML who had productivity income loss paid an uninsured average of $1786  in lost income per month compared to $708  reported by patients with MDS (P < .05). Compared with participants with MDS, participants with AML were younger  and more likely to be employed in either full or part‐time work at baseline . Fewer than 10% of all patients who had alloSCT—and were working at baseline—returned to work within a year. In addition, participants with AML reported greater caregiver productivity losses such as foregone employment, use of vacation time, or unpaid leave for at least 6 months compared with caregiver impacts for participants with MDS . Mean hospital days over the first 6 months of treatment were similar for patients with AML and MDS .When compared to MDS, the mean out‐of‐pocket expenses  were higher for patients with AML at month three ($559 vs $239; 4The results from this study suggest that data on patient‐reported QoL and SES can improve the accuracy of risk models and that scores from the EQ‐5D‐3L's visual analogue scale are the most important predictor to include in post‐remission survival models. The VAS is a subjective measure reflecting a patient's own concept of QoL. Our results suggest that including the VAS or other patient‐reported QoL measures can improve the accuracy how risk is communicated to patients. The novel finding that the VAS was the most important predictor also raises questions about how well the QoL instruments represent outcomes that are meaningful to patients.The instruments used to measure QoL in this study were found to be only moderately reliable and the EQ‐5D‐3L notably suffered ceiling effects that often indicates agreeability bias. The EQ‐5D‐5L has been developed since this analysis in an effort to mitigate ceiling effects in other disease areas. Our findings concur with the literature suggesting that measuring QoL for AML may require more specific instruments due to the severity of the disease and the wide range of treatments and outcomes implied over time , 22, 23.Our study is limited by missing responses arising mostly from discontinuity in study staffing. Despite this limitation, sufficient data were captured to show socioeconomic and financial disparity in this cohort. This is a novel accomplishment for this disease area, highlighting potential for including patient‐reported outcomes in future studies. The response rates were similar to those reported from other studies of these diseases with more frequent missing values for individuals with poorer survival outcomes such as AML patients who did not receive induction therapy, or whose therapy did not result in CR1. There were, however, lower response rates for income and race/ethnicity questions than other baseline demographic reply items. Our results are therefore conservative in estimating the extent of disparity for AML patients and overrepresent outcomes for healthy individuals of higher SES.The potential for QoL and SES variables to improve the accuracy of survival models warrants further attention. QoL outcome measures should be routinely obtained in clinical trials and the question on how meaningful those outcomes are needs to be robustly explored. Collecting information on SES from patients in research studies may improve population outcomes with information on disparity or potential gaps in unemployment insurance coverage. In Canada, any out‐of‐pocket expenditure greater than 5% of a person's net income is considered catastrophic and requires policy to protect those affected  The infoThe authors declare no conflict of interest.Dr Couban, the principal investigator for the TFRI prognostic risk study, died before this publication. He was a proponent in the advancement of our understanding of patient‐relevant outcomes and was enthusiastic about sharing these results with the hematology community. His influence on the lives of patients and grace of leadership guided our collaboration.Sonya Cressman, Stephen Couban, Stuart Peacock, Donna Hogge, Mark Minden, and Aly Karsan designed the research. Sonya Cressman, Emily McPherson, Khalif Halani, and Jing Yi Weng analyzed the data. All authors participated in the interpretation of the findings and the writing of the manuscript.Supporting informationClick here for additional data file.


Danaus plexippus), a species that possesses a magnetic sense, locate their overwintering sites in Central Mexico using inherited geomagnetic map cues. We examined whether overwintering locations and the abundance of monarchs changed with the natural shift of Earth's magnetic field from 2004 to 2018. We found that migratory monarchs continued to overwinter at established sites in similar abundance despite significant shifts in the geomagnetic field, which is inconsistent with monarchs using fine‐scale geomagnetic map cues to find overwintering sites. It is more likely that monarchs use geomagnetic cues to assess migratory direction rather than location and use other cues to locate overwintering sites.How first‐time animal migrants find specific destinations remains an intriguing ecological question. Migratory marine species use geomagnetic map cues acquired as juveniles to aide long‐distance migration, but less is known for long‐distance migrants in other taxa. We test the hypothesis that naïve Eastern North American fall migratory monarch butterflies ( Secular shifts in the Earth's geomagnetic field combined with a lack of change in abundance in the overwintering habitats of the migratory monarch butterfly indicate that it does not use an inherited geomagnetic map sense to locate overwintering sites. This problem is exacerbated for migrants that voyage on their own and that cannot rely on conspecifics that have previously completed the journey. One proposed mechanism facilitating migration for naïve migrants is via the use of a magnetic map, a set of instructions or cues that allows animals to navigate using parameters of the Earth's magnetic field  in Eastern North America potentially use geomagnetic map cues to migrate to overwintering sites in Central Mexico . The total area (ha) is used as an estimate of relative yearly abundance , which provides historical data since 1900 based on date, latitude, and longitude  via a general linear model (glm) in R , there is no long‐term geomagnetic site specificity for monarch butterflies. The results from this natural displacement study are inconsistent with fall Eastern North American monarchs possessing a long‐term  inherited innate magnetic map sense to locate the same overwintering sites in Mexico year after year Figure . In contThe behavior of monarchs could be like the behavior of naïve individuals of other migratory species, for example, sea turtles and salmon, that use geomagnetic map signatures to locate sites during migration Putman, . These sThis type of inherited, annually updated magnetic map mechanism could also involve the use of a very broad scale map sense  potentially explains the capability of monarchs to find the same sites each year despite secular variation, several aspects of the monarch migration make these possibilities unlikely. It is unlikely that monarchs use yearly recalibrated, inherited geomagnetic map cues. Geomagnetic parameters  showed mean yearly shifts in different directions and magnitudes that would be sufficient to alter yearly overwintering abundance at the current overwintering sites Figure . While bIt is also unlikely that fall monarchs possess an inherited large‐scale (100 s of km) magnetic map sense  to maintain a southward flight heading during migration until they reach the border between the United States and Mexico. They may then use the geography of Mexico  to get funneled to their overwintering sites while continuing to fly in a southerly direction Calvert, . Once neOne key possibility is that monarchs might recognize and locate their overwintering sites via habitat selection, as they may be looking for specific microclimates while flying south, which are provided by these overwintering areas. An important aspect of the microclimate at overwintering sites is that it provides temperatures that are cold enough to keep metabolic demands low during overwintering, produce cold conditions that can recalibrate the time‐compensated sun compass for northward oriented flight during the spring remigration ; writing – review and editing . Adam F. Parlin: Formal analysis (supporting); visualization (lead); writing – review and editing . Stephen F. Matter: Conceptualization ; formal analysis ; visualization (supporting); writing – original draft (lead); writing – review and editing .The authors declare no conflicts of interest.


Accordingly, the end of the 1990s and the early 2000s saw a surge of research and syntheses on the ecological linkages between above‐ and belowground subsystems , foliar herbivory can cause plants to release carbon‐rich molecules into the soil. This observation led to predictions that aboveground herbivory should stimulate the activity of soil microbial communities, which in turn may increase the size of the soil inorganic nitrogen pool available to plants  that the plant produces both above‐ and belowground and how these resources enter the soil, are degraded, and feed back to plant growth. The second has focused on the mechanisms of such interactions and, more specifically, how plant physiological changes, such as plant defence strategies or the production of particular primary and secondary metabolites, mediate above‐ and belowground interactions between herbivores and higher trophic level organisms (Soler et al., Moreover, to approach the conundrum of the evolutionary route to aboveground–belowground interactions is to detail a standardized method to measure AG‐BG—as has been done for other plant functional traits (Pérez‐Harguindeguy et al., In sum, as Dante already hinted at, plant‐mediated aboveground–belowground interactions can have widespread effects on community structure, population dynamics, and ecosystem functioning by connecting two otherwise separated subsystems. Research so far has highlighted that there is a high degree of taxonomic and ecological context dependency in such interactions and a relatively high amount of natural genetic variation among plant species. How such variation is maintained across sites and whether AG‐BGs are subject to different selection pressures depending on local ecological conditions Figure  should b


Varenicline is an effective treatment for smoking cessation. While clinical trials did not confirm a causal role, case reports suggested a possible link of varenicline with neuropsychiatric adverse drug events (NPAEs). This study aims to investigate the risk of NPAEs associated with varenicline initiation among the general population in a real‐world setting.We conducted a sequence symmetry analysis (SSA) based on the University of Groningen IADB.nl prescription database. We selected incident users of both varenicline and marker drugs for NPAEs, including depression, anxiety and sleep disorder within different time‐intervals. Adjusted sequence ratios (aSR) were calculated for each time‐interval.Within 365‐days' time‐interval 1066 patients were incident users of both varenicline and NPAE marker drugs. In total, 505 patients were prescribed varenicline before NPAE marker drugs and 561 vice versa . After adjustments for trends in prescriptions, overall a null association was found . Regarding specific NPAEs, no increased risks were found for depression nor anxiety within any time‐interval. A small transient increased risk was found for sleep disorders, particularly in earlier time‐intervals 3 and 6 months . Subgroup and sensitivity analyses showed similar findings.Varenicline initiation was unlikely to be associated with an increased risk of taking anti‐depressants nor anti‐anxiety drugs. Yet a small, but statistically significant, transient association with drugs for sleep disorders was noticed, possibly associated with withdrawal symptoms caused by smoking cessation. In a real‐world setting, initiation of varenicline was not associated with an increased risk of severe adverse events like depressions or anxieties.A possible transient increase in sleep disorders should be taken into account to minimize its influence on the drug adherence.The evidence on neuropsychiatric safety of varenicline from this observational self‐controlled sequence symmetry analysis (SSA) design is consistent with evidence from randomized controlled trials.14β2 nicotinic acetylcholine receptors.Although the prevalence of tobacco use has been declining in recent years,However, subsequent post‐marketing reports related to neuropsychiatric adverse events (NPAEs), such as depression, anxiety, sleep disorder and even suicide, among varenicline users raised concerns about the neuropsychiatric safety of varenicline.Although ICSRs are important for signal detection of adverse drug reactions (ADRs), it is difficult to establish the association and compute incidence rates or risks.Therefore, assessing whether NPAEs occur by varenicline in the real‐world is necessary. To our knowledge, although several observational studies explored the real‐world neuropsychiatric safety,However, the relationship between varenicline and NPAEs has been studied before neither by SSA design, nor among the Dutch population. SSA has been widely used in recent decade to investigate the ADRs of medications as a signal detection method for pharmacovigilance,This study was to examine whether there is an association between varenicline use and onset of NPAEs in a real‐world setting among Dutch population by using SSA.22.1This study was conducted using the widely researched University of Groningen's pharmacy prescription database IADB.nl, a growing database that comprises a population of approximately 730 000 people from 72 community pharmacies in the northern Netherlands since 1994.2.2The SSA design compares the frequency of initiation of a marker drug (as proxy for an ADR) before and after initiation of an index drug within the same individual. The individuals who were prescribed the index drug before marker drugs were labeled the “exposure → outcome” group. Conversely, those who were prescribed index drug after the marker drugs were labeled the “outcome → exposure” group. The crude sequence ratio (cSR) was the number of patients in the “exposure → outcome” group divided by the number of patients in the “outcome → exposure” group. If there is no association, the distribution of sequence orders is expected to be symmetrical and the cSR is close to 1. Of note, the SSA design is sensitive to changing trends in drug prescriptions over time due to factors like reimbursement policy changes and safety warnings. Therefore, a null‐effect sequence ratio (nSR) was used to adjust for the temporal prescription trends of index and marker drugs for ADRs.2.3As the goal of SSA is to evaluate the relation between two incident events, we needed to identify the incident users of both index and marker drugs. As our index drug, that is, varenicline, was authorized for use by EMA on 26 September 2006, no varenicline was prescribed in the database IADB.nl before 2007. Therefore, in theory, patients with the first recorded prescription of varenicline during the study period were all incident users. Since the marker drugs have long been used for chronic treatment of NPAEs, most of their current users will be captured at the beginning of the study period. To exclude the current users and identify incident users of NPAEs marker drugs, we used the waiting time distribution to determine the run‐in period.2.4This study included all individuals who were incident users of both varenicline (ATC: N07BA03) and any marker drugs as potential treatment for NPAEs including depression , anxiety (N05B) and sleep disorder (N05C) from January 2007 to December 2018 in IADB.nl. The first prescription of varenicline was the index date of varenicline, the first prescription of any of the marker drugs for NPAEs was set as index date of any NPAEs. The first prescription of specific marker drugs for depression, anxiety and sleep disorder were set as index date of specific NPAE. Those who were prescribed the index and marker drug on the same day were excluded as their sequence of varenicline and NPAE is not clear.We defined different time‐intervals  between the initiation of the varenicline and NPAEs marker drugs to explore their association. Therefore, incident users of both varenicline and marker drugs within pre‐set time intervals of each other were included for the SSA.2.5u is the last day of the research period, m and n are the consecutive days of the survey period, d is the time interval between index and marker drugs. Am is the number of individuals being prescribed the index drug first on the m day. Bn is the number of individuals being prescribed marker drugs first on the n day.In this study, cSR was ratio of the number of patients in the “varenicline → NPAE” group to the number of individuals in the “NPAEs → varenicline” group. nSR is the expected SR in the absence of an associations due to the trends in utilization alone.p < 0.05 as the level of statistical significance. All statistical tests were two‐tailed.All statistical analyses were performed using IBM SPSS statistics 25  for Windows. We defined 2.6Stratified analysis was conducted according to different gender and age groups. We considered that several policy changes occurred during the study period: (a) reimbursement of PSCTs: PSCTs were reimbursed in 2011, non‐reimbursed in 2012 and again reimbursed from 2013 onwards. (b) Black box warning: FDA communicated it in 2009 and removed it in 2016; we performed sensitivity analyses by calculating the aSR for each year of the study period, as well as in several year groups. Besides, these sensitivity analyses stratified by specific year also reflected the influence of longer run‐in period on results as the incident users that captured before that year were all excluded. Thus, these analyses could further test the robustness of the results.3In total, there were 6440 patients who initiated both varenicline and marker drugs for the selected NPAEs Figure . Of thesAmong the eligible patients, there were 505 patients in the varenicline → NPAE group and 561 patients in the NPAE → varenicline group. Within time‐interval of 365 days, no statistically significant difference was observed between the two groups. The aSR between varenicline and any NPAEs was 1.00  compared with traditional observational studies.Our results by using SSA further confirmed the neuropsychiatric safety of varenicline about possible risk of depression and anxiety. Clinicians and users of varenicline should however remain aware of increased occurrence of sleep disorder, especially in the first 3–6 months after varenicline initiation, which may be the withdrawal symptoms. However, as sleep disorders could be early symptoms of depression,5Our SSA results suggest that the real‐world use of varenicline is unlikely to be associated with risk of depression or anxiety that treated with medication. However, consistent with previous evidence, there was a small transient increased risk of sleep disorder associated with varenicline initiation, particularly in the first 3–6 months. Whether sleep disorder was caused by the adverse effects of varenicline or related to withdrawal symptoms needs confirmation by further studies.The authors declare no conflicts of interest.The authors state that no ethical approval was needed as this study was based on existing database, which was established before according to related ethics criteria.Figure S1 Number of patients newly prescribed varenicline in each year of the study period.Table S1: Prescription sequence symmetry results of the association between varenilcine use and marker drugs for NPAEs within a time window of 1 year, stratified by year.Table S2: Prescription sequence symmetry results of the association between varenicline use and marker drugs for NPAEs within a time window of 365 days, stratified by gender and age groups.Click here for additional data file.


Most clustering methods assume data are structured as discrete hyperspheroidal clusters to be evaluated by measures of central tendency. If vegetation data do not conform to this model, then vegetation data may be clustered incorrectly. What are the implications for cluster stability and evaluation if clusters are of irregular shape or density?Southeast Australia.We define misplacement as the placement of a sample in a cluster other than (distinct from) its nearest neighbor and hypothesize that optimizing homogeneity incurs the cost of higher rates of misplacement. Chameleon is a graph‐theoretic algorithm that emphasizes interconnectivity and thus is sensitive to the shape and distribution of clusters. We contrasted its solutions with those of traditional nonhierarchical and hierarchical (agglomerative and divisive) approaches.Chameleon‐derived solutions had lower rates of misplacement and only marginally higher heterogeneity than those of k‐means in the range of 15–60 clusters, but their metrics converged with larger numbers of clusters. Solutions derived by agglomerative clustering had the best metrics (and divisive clustering the worst) but both produced inferior high‐level solutions to those of Chameleon by merging distantly‐related clusters.Graph‐theoretic algorithms, such as Chameleon, have an advantage over traditional algorithms when data exhibit discontinuities and variable structure, typically producing more stable solutions (due to lower rates of misplacement) but scoring lower on traditional metrics of central tendency. Advantages are less obvious in the partitioning of data from continuous gradients; however, graph‐based partitioning protocols facilitate the hierarchical integration of solutions. Our results suggest that Chameleon may have an advantage over traditional algorithms at thematic scales at which data exhibit discontinuities and variable structure, potentially producing more stable solutions (due to lower rates of misplacement), but scoring lower on traditional metrics of central‐tendency. Chameleon's advantages are less obvious in the partitioning of continuous data, however its graph‐based partitioning protocol facilitates hierarchical integration of solutions. To test these hypotheses, we used a large regional dataset of 7541 plot samples to compare the performance of traditional clustering algorithms  with the Chameleon algorithm. For this evaluation, we used both internal metrics  and the concept of “correctness,” which we apply as the misplacement rate: the proportion of samples that do not cluster with their nearest neighbor. Since we could find no examples of the use of Chameleon in the clustering of vegetation data, we explore the effects of different parameter settings and compare Chameleon's clusters (15‐cluster solution) to the units of a reference classification.22.1Chameleon models the feature space as a k‐nearest neighbor graph (sparse graph) with samples forming vertices connected by links that are proportional to pairwise similarity between samples Figure . The use2.22 encompassing mountains and plateaus of the Great Dividing Range. Average annual precipitation ranges from 460 to 2,344 mm and mean annual temperatures are 3 – 16o C. The area is underlain by a complex series of heavily folded metamorphosed sedimentary rocks deposited from the Ordovician to Devonian periods and interspersed with numerous granite intrusions and, to a much lesser extent, basalts deposited in the Paleogene.The study area encompassed the South East Highlands and Australian Alps Bioregions of the state of NSW, Australia  index for presence‐absence data) between samples Clarke,  using th2.5A very wide range of algorithms has been applied to the classification of vegetation data, with variable performance as measured by internal and external metrics such as cluster homogeneity, silhouette width, species fidelity, etc.  produced by each algorithm retrieved species sets characterizing the units of an established subcontinental‐scale vegetation classification that covers 800,000 kma Keith, , includia Keith, . Its higa Keith, . For eac3A summary of the analytical trials performed and a brief synopsis of the results are contained in Table Trends in the misplacement rate and average within‐cluster homogeneity in Chameleon cluster solutions generated using the single‐link functions are summarized in Figure n) or the number of sub‐partitions (a) in the agglomerative phase were increased, although increasing n disproportionately affected the misplacement rate while increasing a disproportionately affected cluster homogeneity  the utility of the different clustering methods cannot be encapsulated solely in terms of cluster homogeneity and rates of misplacement, (ii) internal evaluators can be misleading in terms of cluster quality, and (iii) the superior performance of Chameleon in elucidating upper‐hierarchical clusters is entirely dependent on selecting appropriate parameters from an infinite range of combinations. The clearest support for our hypotheses was evident in the comparison between solutions derived using Chameleon clusters with those derived by k‐means over the range from 15 to 250 clusters. Chameleon's best 15 and 30 cluster solutions exhibited significantly lower rates of misplacement than those of k‐means at the cost of an increase in heterogeneity Figure , while asensu Peet & Roberts, Accounting for the performance of agglomerative and divisive clustering algorithms is more complicated. First, on the basis of cluster homogeneity and rates of misplacement, our agglomerative algorithm performed better than either Chameleon or k‐means, scoring higher on both metrics across the spectrum of solutions from few to many clusters, while our divisive algorithm scored worse Figure . Both, hComparisons with a reference classification suggest unevenness in the cluster size is more likely to be indicative of chaining because the largest clusters were made up of samples representing multiple classes (as indicated by the range in diagnostic species), some of which are relatively distantly related. This phenomenon was most strongly evident in the agglomerative and divisive solutions Tables , 4, 5. T4.2Although our approach trades‐off cluster homogeneity for improvements in (mis)placement of samples in the cluster, the degree of trade‐off is likely to depend on the structure of individual datasets. In our case study, the misplacement rate achieved by Chameleon was half that of k‐means at the cost of a 10% reduction in cluster homogeneity. If the clusters Chameleon retrieved in our dataset are indeed irregular shapes, then our results suggest they are unlikely to be highly elongated, and variability in our data structure tends toward uneven density rather than irregular shape.A priori, we expect that more heterogenous clusters would mean fewer diagnostic species, the pattern reflected in our results. However, Schmidtlein et al. ; data curation ; formal analysis ; investigation ; methodology . David A. Keith: Conceptualization ; project administration ; supervision .This research was supported by an Australian Government Research Training Program scholarship. We thank Dr Kate Wilson, former Executive Director of Science, NSW Department of Environment and Principal Research Scientist Dr Tony Auld for their support and constructive discussions at the inception of this project. We acknowledge the considerable contribution made by Ken Turner to data curation and thank Greg Steenbeeke for digitising the NSW state vegetation classification species lists. This work has been greatly improved by the inciteful and constructive suggestions we received from our reviewers and editors.


These findings could be understood due to mono‐use of vitamin D, and combination of vitamin D with protein intake and exercise would be a better strategy for patients with sarcopenia according to prior experience.I2 = 71%) may need a further discussion. According to previous evidence, age might be a potential factor due to the associations between them.It was interesting to read a synthesis of effects of vitamin D monotherapy on sarcopenia in community‐dwelling older adults by Konstantinos Prokopidis et al. (2022),FigureWe did further analysis based on the data set that were reported by Prokopidis In conclusion, this further analysis fosters the understanding of the effects of vitamin D monotherapy for sarcopenia outcome in community‐dwelling older population through exploring the influence of age. Vitamin D supplement may have different effect in older population of different age. This hypothesis may explain the divergent conclusion of previous study on vitamin D in preventing falling. Nevertheless, subgroup analysis could not fully explain the heterogeneity in young‐old population. Regression would be a better method to identify the association between effects of vitamin D monotherapy and age, while our analysis has no power to find the trend due to very limited numbers of studies included in the meta‐regression. Wherefore, large‐scale studies are still needed to reveal how the effects of vitamin D on sarcopenia outcomes in community‐dwelling older population, and identify which age group should take vitamin D cautiously.


Malawi is rapidly closing the gap in achieving the UNAIDS 95‐95‐95 targets, with 90% of people living with HIV in Malawi aware of their status. As we approach epidemic control, interventions to improve coverage will become more costly. There is, therefore, an urgent need to identify innovative and low‐cost strategies to maintain and increase testing coverage without diverting resources from other HIV services. The objective of this study is to model different combinations of facility‐based HIV testing modalities and determine the most cost‐effective strategy to increase the proportion of men and youth testing for HIV.A data‐driven individual‐based model was parameterized with data from a community‐representative survey  of men and youth in Malawi (data collected August 2019). In total, 79 different strategies for the implementation of HIV self‐testing (HIVST) and provider‐initiated‐testing‐and‐counselling at the outpatient department (OPD) were evaluated. Outcomes included percent of men/youth tested for HIV in a 12‐month period, cost‐effectiveness and human resource requirements. The testing yield was assumed to be constant across the scenarios.Facility‐based HIVST offered year‐round resulted in the greatest increase in the proportion of men and youth tested in the OPD (from 45% to 72%–83%), was considered cost‐saving for HIVST kit priced at $1.00, and generally reduced required personnel as compared to the status quo. At higher HIVST kit prices, and more relaxed eligibility criteria, all scenarios that considered year‐round HIVST in the OPD remained on the cost‐effectiveness frontier.Facility‐based HIVST is a cost‐effective strategy to increase the proportion of men/youth tested for HIV in Malawi and decreases the human resource requirements for HIV testing in the OPD—providing additional healthcare worker time for other priority healthcare activities. HoweverRoutine HIV testing often misses men and youth in Malawi . Men areOnly a handful of studies have evaluated the impact of facility‐based HIVST, and most are implemented over a brief time period , 14. It Through the creation of a data‐driven individual‐based model, parameterized with survey data of a community‐representative survey of men and youth in Malawi, we modelled the impact of using facility‐based HIV testing modalities to determine the most cost‐effective strategy to increase the proportion of men and youth testing for HIV.22.1This individual‐based simulation model was parameterized using the results of a community‐representative survey of 1180 Malawian men ages 15–64 years) and 300 young women (ages 15–24 years). The survey was conducted from August to October 2019 across 36 randomly selected villages in Central and Southern Malawi using a multi‐staged sampling design. The parent study was designed to assess utilization of facility‐based health services over the past 2 years, offer and uptake of HIV testing services, reasons for testing or not and willingness to use an HIV self‐test. Additional details regarding the parent study have been published elsewhere [4 years an∼45 per village, although some villages had fewer than 45 men due to small village size) and age categories: young men ; middle‐aged men ; older men ; and young women .Eligibility criteria included: (1) aged 15–64 years for men or aged 15–24 for women; (2) current resident of the participating village; and (3) spent >15 nights within the village in the past 30 days. Those who self‐reported as ever testing HIV positive were excluded since they fall outside the target population for HIV testing strategies. Random selection was stratified by village (2.2n = 1480). Characteristic variables included age, sex and numerous questions regarding facility attendance history, such as the date and reason for the visit, whether HIV testing was offered and/or accepted, and whether the visit was as a client or a guardian. Therefore, each simulation reflects the demographics, patient journey and HIV testing history of individuals from this community representative survey. This allows us to understand the likely result of different facility‐based HIV testing strategies at different times. The simulations were scaled by a factor of 100 to aid interpretability for a total simulated population of 148,000.Characteristics were assigned to each individual in the model using survey results (2.3Survey data included facility attendance dates for the four most recent visits within the past 4 years (whether as client or guardian), as well as the total number of visits over a 24‐month period prior to the survey. Given likely recall bias for visits >12 months ago, this analysis only included visits within the last 12 months. For every visit date assigned, the visit reason, whether the visit was as a client or a guardian, was recorded and assigned to the individual in the model. The individual simulations were programmed in MATLAB v9.7 .2.4We estimated the number of healthcare worker hours required to implement each facility‐based testing scenario , and the personnel required to implement these guidelines. Facility‐based HIVST, as implemented to date , has takVarying coverage of standard  PITC and HIVST from 5% to 90%Targeted to OPD clients, guardians or bothTargeted to different periods Therefore, the scenarios included variations of the following:A set of 79 mutually exclusive intervention combinations of the above three factors were considered Table . AssignmWithin the model design and for each scenario, there are noted elements which used randomization to assign tests to visits. As such, to achieve a better overview of what a typical implementation may look like, each scenario was iterated 100 times and the average results for all iterations were exported for analysis.2.8To calculate the total costs for each scenario, we accounted for the full cost of test kits, including professional‐use tests prescribed by Malawi's HIV testing algorithm, Determine HIV 1/2 (Alere), Uni‐Gold HIV (Trinity Biotech) and OraQuick HIVST (OraSure), staff time, consumables and overhead estimated from previous work , 15. The2.9The National Health Sciences Review Committee of Malawi (number 2338) and the University of California Los Angeles Institutional Review Board (number 20–001606) approved the study activities. All eligible individuals completed a written informed consent form immediately following screening procedures. For individuals between 15 and 18 years of age, guardians provided written consent.3Of the 79 scenarios tested, 61 increased the proportion of men and youth tested in the past year compared to the baseline PITC scenario (in which PITC is offered at approximately 50% of visits) Table . The sceAmong the HIVST‐only scenarios, only testing those not tested in the past 12 months  would reduce testing coverage to 74% of individuals being tested within a 12‐month window (vs. 83% with no restrictions). The reduction is largely due to when individuals’ visit health facilities and not returning after they would become eligible for testing (i.e. >12 months since the last test). Limiting testing to those who have not been tested in the past 6 months increased the proportion tested to 81% of individuals getting tested within a 12‐month window. There was limited marginal gain when further loosening testing eligibility criteria .At the highest HIVST kit price $1.80), the only cost‐saving scenario was where PITC covers 10% of all OPD client visits at random (for clients and guardians) and increases to 60% of all visits receiving PITC at random during the highest volume 3 months of the year , the scenario in which PITC covers 5% of all visits at random during the year for both clients and guardians and provides HIVST to clients only during the highest volume 3 months of the year for clients only (not guardians) (scenario 7) is considered cost‐saving compared to baseline PITC. Similarly to when the HIVST kit price was $1.80, the subsequent four scenarios on the cost‐effectiveness frontier were all sub‐scenarios of scenario 8 : limited to those not tested in the last 12 months , the last 6 months , the last 3 months  and not limited by time since the last test .At the lowest HIVST kit price ($1.00), the scenario in which HIVST is offered for 12 months  was considered cost‐saving compared to baseline PITC, resulting in a 20% reduction in total costs compared to the current coverage of PITC alone. The subsequent three scenarios on the cost‐effectiveness frontier were the remaining versions of scenario 8: limited to those not tested in the last 6 months , the last 3 months  and not limited .4In this data‐driven, individual‐based model, we assessed the cost‐effectiveness of multiple implementation strategies at different HIVST price points for HIV testing in OPD settings in Malawi that would increase testing coverage among men and youth. We found that almost all facility‐based HIVST scenarios increase community‐level HIV testing coverage among men and youth when implemented in OPD settings. Men and youth are historically underserved by current PITC programmes, as standard PITC achieves poor coverage within busy OPD settings , 17. TheThe only PITC‐based scenarios that can increase the proportion of men and youth tested to the same degree as year‐round HIVST require a significant increase in personnel requirements. The reduction in healthcare worker time required for HIVST compared to the current status quo is a significant advantage to the HIVST scenarios, requiring up to 70% fewer personnel than the current standard of care. Saved human resource capacity from HIVST implementation could be used for other activities like patient linkage, treatment support, to provide support elsewhere in the facility or to additional testing strategies, such as index testing or initial HIV screening to increase testing yield.Our findings contribute to a growing body of evidence on how facility‐based HIVST can contribute to achieving the UNAIDS first 95 goals for those traditionally unreached by HIV services. HIVST is consistently shown to increase testing rates in comparison with standard PITC models, even in randomized controlled trials where providers receive additional support for implementing PITC , 14, 21.Our study has several limitations. First, for different standard PITC coverage levels, we randomly assigned individuals to be offered an HIV test, and the uptake of that test was dependent on their survey response. In reality, PITC coverage among outpatient visits is unlikely to be completely random. Any selection in favour of someone at increased risk of HIV infection would result in increased cost‐effectiveness of any scenarios, including PITC, through a reduced cost per positive test. However, the sensitivity of any type of screening needs to be weighed against the additional time required to administer it, which could increase human resource requirements and offset the reduction in cost per positive test. Within our test assignment, we also did not offer HIVST to PITC refusers given our assumptions about implementation from the facility‐based HIVST trial . Future 5Facility‐based HIVST in the OPD is cost‐effective and can significantly increase access to HIV testing for men and youth in Malawi. The feasibility of covering all OPD visits with HIVST will depend on the available budget for test kits. Additional investment in capacity to implement year‐round facility‐based HIVST, limiting testing based on time‐since‐last‐HIV‐test and introduction of lower‐priced HIVST products should be prioritized to maximize the impact of facility‐based testing strategies.The authors declare that there are no competing interests.BEN, ND and KD conceived the study. KB, MM, SK, CS, ND and KD acquired and analysed data for the model. BEN, AdN, MB and GR developed the model. BEN, AdN, CWC, CAR and KD interpreted model results. BEN, AdN and KD wrote the first draft of the manuscript. MB, KB, MM, GR, CWC, SK, CS, CAR and ND contributed to the writing of the manuscript. All authors read and approved the final manuscript.The Foreign, Commonwealth and Development Office of the United Kingdom of Great Britain and Northern Ireland funded the study (grant number: 300380), as well as the United States Agency for International Development (Cooperative agreement 72061221CA00010). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.


OzFlux is a network not only for ecosystem researchers, but also for those ‘next users’ of the knowledge, information and data that such networks provide. Here, we focus on eight lessons across topics of climate change and variability, disturbance and resilience, drought and heat stress and synergies with remote sensing and modelling. In distilling the key lessons learned, we also identify where further research is needed to fill knowledge gaps and improve the utility and relevance of the outputs from OzFlux. Extreme climate variability across Australia and New Zealand (droughts and flooding rains) provides a natural laboratory for a global understanding of ecosystems in this time of accelerating climate change. As evidence of worsening global fire risk emerges, the natural ability of these ecosystems to recover from disturbances, such as fire and cyclones, provides lessons on adaptation and resilience to disturbance. Drought and heatwaves are common occurrences across large parts of the region and can tip an ecosystem's carbon budget from a net CO2 sink to a net CO2 source. Despite such responses to stress, ecosystems at OzFlux sites show their resilience to climate variability by rapidly pivoting back to a strong carbon sink upon the return of favourable conditions. Located in under‐represented areas, OzFlux data have the potential for reducing uncertainties in global remote sensing products, and these data provide several opportunities to develop new theories and improve our ecosystem models. The accumulated impacts of these lessons over the last 20 years highlights the value of long‐term flux observations for natural and managed systems. A future vision for OzFlux includes ongoing and newly developed synergies with ecophysiologists, ecologists, geologists, remote sensors and modellers.In 2020, the Australian and New Zealand flux research and monitoring network, OzFlux, celebrated its 20 The Australian and New Zealand ecosystem observation network—OzFlux—celebrated 20 years making ecosystem measurements in 2020. Important insights and new knowledge from this 20‐year period were identified and discussed as eight key lessons. Our vision for the future of OzFlux is also discussed, and includes training the next generation and providing ecosystem data to improve understanding of Australia's and New Zealand's rapidly changing environments. Two decades on from its establishment in 2001, OzFlux has matured into a network that supports research about Australia's and New Zealand's unique ecosystems, provides key data for Southern Hemisphere terrestrial systems, and observations for some ecosystems subject to an extreme and highly variable climate. The OzFlux community has created an observing network and platform to enable scientific discoveries by generations of researchers and to deliver relevant and robust data and information for researchers, resource managers and policymakers, now and into the future. Through OzFlux, this research community has also transformed its approach to data sharing, acknowledging the challenges this can involve and developing solutions to address these, alongside demonstrating the significant benefits that flow from ensuring that data complies with FAIR (Findable Accessible Interoperable Reusable) principles  ecosystem response, resistance and resilience to disturbance and stress; (2) ecosystem processes that modulate water availability, runoff and productivity and (3) net greenhouse gas emissions and the potential for these ecosystems to mitigate climate change and support ecosystem services and food production in the future. This aim reflects that our primary audience for these lessons is the ecosystem research community, however we anticipate that those ‘next users’ of the knowledge, information and data that networks such as OzFlux support may also find benefit from these insights. In distilling the key lessons learned, we also identify where further research is needed to fill knowledge gaps and improve the utility and relevance of the outputs from OzFlux.2The OzFlux journey began in the early 1990s when Australian and New Zealand researchers embarked on longer‐term micrometeorological field campaigns and studies in agricultural, natural and modified forest, native grassland and wetland ecosystems. This research revealed gaps in our knowledge of ecosystem dynamics and feedbacks with climate and hydrology at multiple timescales, across the diverse landscapes of New Zealand and Australia  a mThese foundational flux tower sites sowed the seeds of OzFlux, which expanded to a continental network when TERN  was funded in 2009. This funding provided the capital and institutional investment needed to support the ‘hard’ infrastructure of around a dozen flux towers and supersites across Australia  recovers to pre‐fire levels, despite fires having little effect on respiration or nutrient cycling   and a resultant increase in more frequent and intense heatwaves , whereas the nearby hummock grasslands become a CO2 source if the annual rainfall falls below the pivot point of 506 mm yr−1  or other stress as was demonstrated at the temperate, wet sclerophyll, managed forest at Tumbarumba, where long‐term drought coincided with an insect attack . This dairy expansion, which has to a large extent replaced extensive sheep farming in the lower and flatter regions of the country, is overwhelmingly based on rotational grazing practice, involves active nutrient and feed supplement management and is in some drier regions supported with irrigation of pastures. Managing the land for food production has thus accelerated and intensified carbon, nutrient and water cycles and increased the country's agricultural greenhouse gas emissions by 17% from 1990 to 2019  of carbon. To assess whether an agroecosystem gains or loses carbon over time, these exports and imports need to be quantified together with NEE to obtain the net ecosystem carbon balance (NECB). A productive system is usually a net COWater fluxes are of critical concern in agroecosystems, where irrigation decisions are informed by balancing crop water use with yield‐based revenue, irrigation costs and regulatory limits for nutrient leaching. There are concerns that the practice of irrigation, increasingly widespread in NZ, may lead to net carbon losses, and soil‐core sampling studies point in this direction  and N2O . Technological challenges and instrumentation costs have limited the usage of the eddy covariance method for measuring fluxes of these non‐CO2 greenhouse gases; hence, other micrometeorological methods have predominantly been applied within the OzFlux network. Laubach and Hunt  most of the time, even in the absence of cattle. Net emissions of similar magnitude have recently been found on farms in the north of NZ . The source of these CH4 emissions is unknown, and therefore it is not clear whether they are related to agricultural management. The flux gradient technique has also been applied to measure nitrous oxide emissions from dairy pasture  that introduced the first suite of satellite‐based global ecology products for long‐term monitoring of ecosystem functioning, phenology, disturbance and plant stress  to better understand arid vegetation responses to Australia's climate extremes , gravitational total water storage (GRACE), VIs (MODIS) and solar‐induced chlorophyll fluorescence  with OzFlux tower derived NEP. They analysed the hydroclimate drivers and pulse response behaviour of carbon fluxes during the big wet and reported that semi‐arid Australian net CO2 uptake was highly transient and rapidly dissipated by subsequent drought. The accuracies of the remotely sensed CO2 retrievals and the atmospheric transport models are approaching the levels needed to constrain CO2 fluxes to estimate net biome productivity (NBP) from the natural biosphere . These continent‐wide green flushes can contribute significantly to the global land carbon sink and induce sea‐level anomalies, as occurred in 2010–2011  and the Australian Phenocam Network (http://phenocam.org.au/). SpecNet sites are equipped with hyperspectral instruments and play important roles in linking in situ optical measures  from tower platforms with flux observations, to explore mechanistic and scaling relationships  for inversion studies and advanced hyperspectral sensors for canopy traits. These new remote sensing advances will be vital to scale knowledge  provide sub‐daily, 10‐min image acquisition frequencies in near real‐time across Australia, enabling integration with diurnal fluxes for refined insights into ecosystem dynamics. A metric of canopy structure, canopy clumping index, was recently retrieved from sub daily measures from the Deep Space Climate Observatory (DSCOVR) satellite and evaluated at OzFlux sites  soil moisture  with satellite remote sensing, would enable the development of new theory to understand leaf growth dynamics under changing water availability. Measurements of hydraulic traits across the OzFlux network   than the tropical savanna at AU‐How, which is surprising given C4 grasses (high WUE) dominate the understory of the savanna ecosystem. However, these grasses are largely annual and are only active 4–5 months of the wet season, whereas the evergreen C3 woody species of Australia's temperate forests are active all year , and WUE increased by 16% over 18 years, whereas the tropical savanna site only increased by 6% . As climate variability increases, there is a clear imperative to maintain long‐term monitoring sites and invest in modelling systems structured to the physiological properties of Australian and New Zealand vegetation to assess their response to increasing climatic variability and disturbance. Australian ecosystems have shown a degree of resilience to date  inform the science and models needed for accurate ecological forecasts and longer‐term projections of responses to climate extremes; (2) document recovery from disturbances, and evaluate potential new land management strategies and longer‐term trends in the effects of observed climate change and variability—this demands multi‐decadal and continuous observations; (3) diagnose interannual variability in the carbon cycle and net greenhouse gas emissions, and verify carbon market products and greenhouse‐gas mitigation approaches; (4) evaluate and improve models of terrestrial ecosystem feedbacks to climate change, and (5) evaluate and improve simulations of the feedbacks between the land and atmosphere in the context of short‐duration heatwaves and drought.https://science.uq.edu.au/neps). This could facilitate integration of environmental observations with predictive modelling, thus improving environmental risk management. New streams of earth observing satellite data are emerging from advanced sensors. However, the interpretation of their underlying ecological signals requires continued validation with ground‐based sensors and leaf‐level measurements. Using spectral indices and more direct observations of vegetation productivity through SIF provide excellent prospects for better detection of ecosystem stress . OzFlux will continue to participate as a key provider of ground stations in the Southern Hemisphere and will provide opportunities for further synergies between remote sensing and ecosystem ecologists.Ecosystems are expected to experience continued long‐term climate change and greater variability along with increased disturbance leading to a loss of ecosystem services. To best maintain our ecosystems and their services, we must anticipate and plan for these changes using predictive modelling and ecological forecasting. Developing this capability is crucial and will require forecasting (over the near term) and projections over multidecadal time scales) using real‐time flux information (OzFlux), ecological observing infrastructure (e.g. TERN), new and emerging satellite information and a new iterative model forecasting paradigm (Dietze et al., Ongoing collaboration between ecophysiologists and ecosystem flux researchers is leading to improved mechanistic understanding of the role of the terrestrial vegetation in the annual and inter‐decadal hydrologic cycle and the carbon balance across a wide range of ecosystems.Of emerging interest is the connection of physiological/hydraulic traits to the dynamic role of the subsurface in regulating surface ecosystem fluxes and vegetation health. For example, an increasing body of international evidence illustrates how groundwater, deep soil moisture (Mu, De Kauwe, Ukkola, Pitman, Guo, et al., A significant proportion of Australia's total ecosystem biomass (ca. 30%–50%, Spawn et al., 2 and water cycles to monitoring other greenhouse gases, especially emissions of CH4 from wetlands and N2O from agricultural systems as highlighted in the lessons above. These potent greenhouse gases can now be measured at temporal and spatial scales that are relevant to land management and planning for mitigation of climate change.Ecosystem observatories are moving beyond COThere is currently a high demand for new researchers with skills in environmental monitoring, sensors and data analysis; however, it is a challenge to sustain training of postgraduate students and our capacity in the discipline of global change biology. Recruitment of new talent needs to start at the undergraduate level or earlier, to ensure a flow of quantitatively skilled researchers who are passionate about ecosystem science. Educational collaborations among engineers, atmospheric scientists, hydrologists, ecologists, physicists and others will set the stage for the next generation of environmental leadership and stewardship. OzFlux will continue to play a major role in training this next generation and in providing the ecosystem data which scientists, the public and managers/government can rely on in understanding our rapidly changing environment in Australia and New Zealand.This manuscript was designed after a 20 years of OzFlux celebration conference held in 2020. The manuscript was prepared by Beringer, Moore and Cleugh with input from all co‐authors. Each lesson was compiled by a section lead as follows; Cleugh led ‘the genesis of OzFlux’, Griebel led Lesson 1, Cleverly led Lesson 2, Moore led Lesson 3, Campbell led Lesson 4, Grover and Laubach led Lesson 5, Huete and van Niel led Lesson 6, De Kauwe and Kirschbaum led Lesson 7 and Hutley led Lesson 8.