The frequency and duration of heatwaves are increasing because of human activities. To cope with the changes, species with longer generation times may have to rely on plastic responses. The probability that their responses are adaptive is higher if the species have experienced temperature fluctuations also in their evolutionary past. However, experimental studies investigating responses to heatwaves often use exposure times that are significantly shorter than recent heatwaves. We show that this can lead to faulty conclusions and that the duration of higher temperature has to be considered in experimental designs. We recorded the response of threespine stickleback to prolonged duration of higher temperature during the breeding season, using a population that has experienced large fluctuations in temperature in its past and, hence, is expected to endure temperature changes well. We found males to adaptively adjust their reproductive behaviours to short periods of higher temperature, but not to longer periods that extended across two breeding cycles. Males initially increased their reproductive activities—nest building, courtship and parental care—which ensured high reproductive success during the first breeding cycle, but decreased their reproductive activities during the second breeding cycle when exposed to sustained high temperature. This reduced their courtship success and resulted in fewer offspring. Thus, a species expected to cope well with higher temperature suffers fitness reductions when the duration of high temperature is prolonged. The results stress the importance of considering the duration of extreme environmental conditions when investigating the impact that human activities have on species. Responses to short‐term exposures cannot be extrapolated to assess responses to longer periods of extreme conditions. The frequency and duration of heatwaves are increasing because of human activities. We show that stickleback males are able to adaptively adjust their reproductive behaviours to short‐term increases in temperature, but not to longer‐term periods that extend across two breeding cycles. This highlights the importance of considering the duration of extreme environmental conditions when investigating the impact of human activities on species Species with long generation times in relation to the rate at which the environment is changing may not be able to adapt through genetic modifications but have to rely on plastic adjustments , and such conditions are expected to increase in the future  using Plexiglas traps ). A temperature of 19°C or higher is occasionally attained when air temperature exceeds 25°C for several days. However, during the preceding 9 years, temperatures of 19°C or higher had not lasted more than maximum 5 days .When males came into reproductive condition, as determined by the development of nuptial colouration, we measured their size (standard length and weight) and transferred them to 10‐L aerated tanks in climate chambers, one male per tank. We exposed them to one of four temperature treatments during two breeding cycles, 18 males per treatment: (1) constant normal temperature of 14°C, NN, (2) constant high temperature of 19°C, HH, (3) switch from high to normal temperature between breeding cycles, HN and (4) switch from normal to high temperature between cycles NH. The constant normal temperature served as the control and the constant high temperature as the long‐term treatment, and the two treatments with switches as short‐term treatments where the higher temperature occurred either early or later during the breeding season. A temperature of 14°C represents average natural temperature in the spawning habitat during the breeding season, as measured in June during 9 years preceding the study  filled with sand and filamentous algae, 2.3When a nest was ready, we recorded the courtship behaviour of the male towards three consecutive gravid females, with a 30 min break between presentations. Some females were reused among males, which was considered in the analyses. Each female was enclosed within a perforated, transparent jar and the presentation lasted for 10 min. Females had been kept in the outdoor facility under natural temperature conditions until 1–2 days before experimentation, when they were transferred to an 10‐L aerated tank held at the same temperature as the experimental male tank. We video recorded the courtship behaviour of the male and analysed his behaviour using the software BORIS .After the third courtship recording, we released the female and allowed her to spawn with the male. We recorded the time until spawning occurred. If the female did not spawn within 2 h, we assumed she was not interested in the male and replaced her with a new female. Spawning time was in these cases noted as the maximum time, 120 min. We measured the number of eggs spawned by gently removing all eggs from the nest 2 h after spawning—when the eggs had hardened—and weighing the total clutch to the nearest 0.01 g .We allowed the males from the first breeding cycle to complete a second cycle by providing them with fresh material for nest building, and repeated the procedures from the first cycle. Four males did not enter a second cycle; one at normal temperature, and three at high temperature. In the analyses, qualitatively similar results are gained if these males are removed from the analyses or maintained as missing values during the second cycle. Given that we do not know the reason for the males not entering a second breeding cycle, we present the more conservative results with the males removed from the analyses. The total number of eggs received across the two breeding cycles did not differ among treatments , courtship , and parental care . Males built a nest faster, courted more vigorously, and spent more time on parental care . During the second cycle, time until spawning did not differ from the first cycle at constant normal temperature (NN) but was extended at constant high temperature (HH) and when temperature dropped (HN), while the time was shortened when temperature rose (NH)  Table . Thus, tF1,70 = 1200.71, p < .001) and the second cycle . Hatching success (percent of eggs hatching) did not depend on temperature during the first cycle . During the second cycle, males at constant high temperature (HH) had a lower hatching success than during the first cycle, while males at constant normal temperature (NN) and males experiencing a fall in temperature (HN) showed no change in hatching success (Table The eggs hatched earlier at the higher temperature during both the first (SE) than at constant normal temperature (NN) , falling temperature (HN)  or rising temperature (NH) , falling temperature (HN) , or rising temperature (NH) . Males experiencing a rise or fall in temperature (NH or HN) did not differ in the time it took to complete the two breeding cycles  or in weight loss .Males completed the two breeding cycles faster when maintained at constant high temperature (HH) (18 days ± 1, mean ± 4Our results show that threespine stickleback males adjust their reproductive behaviours—nest building, courtship and parental care—to changes in water temperature. They increase their activity when temperature rises and decrease it when temperature drops, as expected for ectothermic organisms (Dillon et al., During the short spell of high temperature, males increased their reproductive activities irrespective of whether the spell occurred early or late during the breeding season. Thus, our expectation of males being less able to adjust to temperature increases later in the season, due to a gradual decrease in body condition (Candolin, The increased activity during a short spell of higher temperature was most likely a consequence of faster metabolic rate, as is generally the case in ectotherms (Dillon et al., The cause of the inability of males to maintain high reproductive activity under sustained high temperature—during the second breeding cycle—was probably exhaustion. This is supported by males losing more weight in the sustained high temperature treatment than in the other treatments. In addition, the nest building period between the two breeding cycles was prolonged for males on high temperature during the first cycle, which indicates the need for a longer recovery time. This prolongation partly cancelled out the benefit of a shorter parental care period, which otherwise could increase the number of breeding cycles that males could complete (Candolin, These results indicate that threespine stickleback males are able to cope with shorter spells of higher temperature, but not when their duration is prolonged. Yet, such extreme conditions are becoming increasingly common. The investigated stickleback population has apparently adapted to short periods of high temperature, as these have occurred also in the past, but not to their prolongation. Thus, responses to short‐term extreme conditions cannot be used to predict responses to longer‐term changes for the investigated species. This stresses the importance of considering the duration of extreme conditions, such as heatwaves, when evaluating the ability of organisms to cope with the ongoing climate change. Investigations often focus on the limits of temperature tolerance, while effects of the duration of high temperature is seldom considered (Lawson et al., The results further stress the importance of considering the past history of species when predicting and assessing responses to extreme conditions (Chevin & Hoffmann, To conclude, our results show that threespine stickleback males are able to adaptively adjust their reproductive behaviours to short‐term increases in temperature, but that the prolonged duration of high temperature poses a challenge that reduces the activity and reproductive success of stickleback. Thus, the average reaction norm that has evolved in the population is insufficient for coping with temperature rises when the duration of high temperature is prolonged. These results emphasise the importance of considering the duration of extreme conditions when assessing the impact of climate change on species. Responses to short‐term exposures cannot be extrapolated to assess responses to sustained periods of extreme conditions.The authors declare no conflict of interest.Appendix S1Click here for additional data file.


Mindfulness‐based Cognitive Therapy (MBCT) is a relapse‐prevention intervention for people experiencing major depression. Three qualitative meta‐syntheses investigating experiences of taking part in MBCT and/or Mindfulness‐based Stress Reduction (MBSR) across different diagnostic populations reported themes including control, choice, group processes, relationships and struggles. As multiple studies have been published since, we aimed to update, systematically review and synthesize the experiences of participants with depression taking part in MBCT.Four databases were searched systematically  up to and including 12 November 2021. Twenty‐one qualitative studies met the review criteria. All papers were rated as fair using a quality appraisal tool. Meta‐ethnography was applied.Across 21 studies of participants with current or previous depression who had participated in MBCT, three overarching themes were developed: ‘Becoming skilled and taking action’, ‘Acceptance’ and ‘Ambivalence and Variability’. Participants became skilled through engagement in mindfulness practices, reporting increased awareness, perspective and agency over their experiences. Participants developed acceptance towards their experiences, self and others. There was variability and ambivalence regarding participants' expectations and difficulties within mindfulness practices.Many studies were conducted in MBCT‐research centres that may hold conflicts of interest. Many studies did not address the impact of the participant–researcher relationship thus potentially affecting their interpretations. Studies were skewed towards the experiences of female participants.Our findings help to enhance participant confidence in MBCT, alongside understanding the processes of change and the potential for difficulties. MBCT is beneficial and provides meaningful change for many but remains challenging for some. This meta‐ethnography of 21 qualitative studies generated three overarching themes.MBCT enables the development of new skills and different ways of responding, as well as a shift towards accepting experiences, self and others.Meaningful change is variable across participants and there is the potential for difficult experiences to arise both during and beyond MBCT.This study gives practitioners a greater understanding of the processes of change, alongside the benefits and challenges of MBCT.We highlight clear implications and include recommendations for practice for MBCT teachers, clinicians and researchers.1Major depression affects approximately 264 million people worldwide and has an estimated lifetime prevalence of 10.8% . This review was conducted in line with both the updated ‘Preferred Reporting Items for Systematic Reviews and Meta‐analyses’ , delivered in a group or one‐to‐one setting, either face‐to‐face and/or via remote methods . The recipients of MBCT could include individuals, couples, or families, provided that all of the remaining inclusion and exclusion criteria were met. Minor amendments to MBCT were acceptable provided they did not deviate from the focus on relapse‐prevention in depression or extensively from the manual  and (depress*) and . MeSH terms were selected in PsycInfo and Medline  with ‘suggested subject terms’ selected instead on Web of Science and CINAHL . There were no prior date limits to enable identification of all relevant papers published up until the date of the search. The search was initially conducted on 2 October 2020, with an updated search completed on 12 November 2021. The updated search followed the same methodology and analysis as highlighted here.N = 21) were emailed to enquire about any further publications, either unpublished or in preparation; all 21 authors replied but no eligible studies were identified. Four authors were contacted for further clarification over study methods , with others across mainland Europe (N = 3) or the USA (N = 4). Nineteen studies included adult samples; two studies included adolescent samples. Only 15 studies reported on gender which was skewed towards female (range 63%–100%). The majority of studies reported on group‐based, face‐to‐face delivery of MBCT (N = 20) with one study delivering online MBCT. Most studies (N = 15) included participants with histories of multiple ‘episodes’ of depression but were either currently free from symptoms (‘full remission’) or experiencing mild symptoms . The remaining studies (N = 6) included participants who were currently experiencing symptoms in line with ‘mild’ to ‘moderate’ severities. Interviews were conducted either post‐MBCT , during follow‐up (N = 6) or at both post‐MBCT and follow‐up . Semi‐structured or open interviews were administered (N = 18); the remaining studies used written questionnaires (N = 1) or a mix of interviews and questionnaires (N = 2). All studies employed qualitative analysis.Study characteristics are in Table One study also included interviews with parents and staff; only the findings from interviews with adolescents were included. Although parents participated in MBCT, this was to better support their child through depression . A consistent finding across studies was that participants felt able to choose which style of practices they engaged with. For example, whilst some described persisting with the longer practices ‘because they allowed time for the mind to slow down and focus’  thoughts and emotions was lessening’  feelings of vulnerability’ or ‘hopelessness’ : ‘Becoming skilled and taking action’, ‘Acceptance’ and ‘Ambivalence and variability’.Our findings replicate and extend the findings of the earlier meta‐syntheses  as transient mental events rather than as truths  with participants. All MBCT teachers, whether in clinical, community or research settings, should ensure that participants are given full opportunity to discuss their expectations of MBCT and whether these can be realistically met during MBCT, to ensure fully informed participation. Further, when facilitating MBCT for people with histories of depression, it is arguably more important to consider the role of expectations. MBCT teachers should maintain an awareness that their clients may hold potentially higher levels of hopelessness and lower expectations of change at the start, during and at the end of MBCT. We encourage MBCT teachers to find a balance between acknowledging the realistic expectations of what MBCT can and cannot offer, whilst also aiming to instil hope in clients as they navigate through the MBCT course. MBCT teachers should discuss the possible logistical, practical and emotional challenges that may arise with taking part and offer further support or alternative options for attendance .Given our findings of the importance of the development of agency and control over thoughts, feelings and experiences, and permission for self‐care, MBCT teachers should work to empower clients who may typically have a strong history of feeling hopeless or powerless. Specifically, during MBCT sessions, MBCT teachers can help their clients to develop a sense of metacognitive awareness of their thoughts, feelings and experiences through explicitly naming and increasing awareness of how they are beginning to recognize and develop their own agency and control. MBCT teachers could actively monitor group dynamics and offer more regular check‐ins regarding the group sense of cohesion and safety, particularly as our findings showed that the belonging to a safe group enabled self‐acceptance and acceptance from others. This may be particularly important for those who are currently experiencing symptoms of depression as our findings showed that this was a more commonly mentioned theme across those studies investigating participants with current symptoms.both mindfulness practices and class discussions. If individuals subsequently decide to still continue with MBCT, it will be important that teachers and participants discuss ways in which support could be offered to participants during MBCT practices, class discussions and in their homework practice. This may involve inclusion of content warnings prior to delivered content or group discussions or explicitly giving permission to participants to pause or sit out of practices or discussions. This may also involve an in‐class discussion around the potential to feel triggered by difficult practices or conversations and providing additional guidance at those times: ad hoc practices around sitting with difficulty or inviting pauses for acknowledgement of the difficulty and group reflection.Additionally, MBCT teachers and participants should discuss their expectations for what may feel triggering  or what might arise during a practice . It will be important that individuals wishing to undertake MBCT are fully assessed in terms of their clinical histories, with an emphasis on explicitly discussing the potential for memories, flashbacks, feelings and thoughts to be triggered during As mentioned in the results, most second‐order constructs were present across multiple studies, which supports the strength of the overarching themes as participants reported changes in line with the underlying principles of MBCT, suggesting that MBCT is working as intended. However, it could also be argued that there may be some questions that are not explored or some participant experiences that are missed; this may be the case for those participants who drop out or do not sign up to an MBCT group. Exploring these perspectives in future research would help to clarify this. Further research could specifically explore how experiences are shaped by current depression severity alongside the core themes. Our findings highlight the importance of considering the qualitative experiences of MBCT, especially in light of our findings around variable change that is individually meaningful, as meaning becomes a difficult concept to quantify.4.2Thirteen studies did not specifically acknowledge the impact of the participant–researcher relationship; thus, we cannot be certain what effect this may have had on the original authors' interpretations. A number of studies included researchers who have been extensively involved in MBCT practice and research whose particular biases, expectations and conflicts of interest may have impacted on study findings. However, the inclusion of studies, which were conducted in non‐expert MBCT centres of research works to mitigate this. There were a number of similarities across the different study characteristics. However, it is noticeable that the concept of ‘acceptance’ was rarely, if at all, discussed within studies from the United States, in comparison to those from the United Kingdom/Europe. These findings may be a result of cultural implications, which may be worth exploring in further research. There were significantly fewer studies focused on adolescent and older adult experiences, where there may also be different considerations and experiences. Gender distribution within studies was skewed towards participants identifying as female. This might be explained by higher proportions of women experiencing depression Kuehner,  or sugge4.3The lead researcher was interested in and experienced in delivering and researching MBCT, which may have impacted on the interpretations made in this synthesis. However, efforts to stay aware of and reflect on this were made through use of the reflective log and in‐team discussions. All studies were required to be written in English which may have meant that we missed some studies. The lead researcher screened all of the titles and abstracts, of which an independent researcher screened 15%, with good agreement between the two researchers' search strategies. Additionally, the lead researcher conducted the coding of the individual studies, which was discussed regularly with the other co‐authors to ensure resolution of any disagreements. It should be acknowledged that in order to enhance researcher objectivity and reduce the chance for researcher error, it would have been beneficial to have had a second researcher conduct both a parallel screening of all the titles and abstracts and the coding of the individual studies. Finally, although unpublished theses and conference abstracts were detected by our search strategy, we did not specifically search any grey literature databases thus may have missed other relevant studies.5Across 21 qualitative studies, we found three overarching themes specifically relevant to participants' experiences of MBCT, including ‘Becoming skilled and taking action’, ‘Acceptance’ and ‘Ambivalence and Variability’. Our findings suggest that whilst some people benefit from developing skills in mindfulness, develop awareness, agency and acceptance of themselves and others, others may have difficulty in practicing mindfulness and attending MBCT classes. This may indicate that MBCT needs to be carefully tailored to individual experiences and expectations in order to maximize relapse prevention. Our findings provide an update and a more specifically tailored meta‐synthesis of qualitative studies for participants with depression participating in MBCT. Our findings help to enhance confidence in MBCT, to further understand the processes involved in change following MBCT and to better understand who may experience difficulties.The study authors have no conflicts of interest to declare.Table S1. PRISMA checklistTable S2. PRISMA 2020 for Abstracts checklist Table S7. Sensitivity analyses based on study characteristics and organized by overarching themes and second‐order constructsTable S8. Step 4. 2nd order categories across studies incorporating author themes, subthemes, descriptions and interpretationsTable S9. Full text screening decisionsTable S10. CASP quality results by studyTable S11. Second‐order construct and example quoteClick here for additional data file.


Numenius arquata) from GPS tag movement patterns using the “recurse” package in R. This package identifies foci of activity (using K‐means clustering) based on revisitations. Using a training data set from an individual of known breeding status, we visually assessed the frequency of revisits to particular locations to identify prebreeding, incubation, chick guarding, and post‐breeding stages to an accuracy of a within at most half a day and thus breeding outcomes. Limited validation was provided by additional field observations. Based on our results, we estimate a low daily nest survival rate of 0.935 during incubation, that only a small proportion of individuals successfully raised young, and that there was a high proportion (26%) of non‐breeders in the population. The Eurasian Curlew is a species of high conservation concern across Europe, and our results concur with recent studies highlighting that population declines are likely to be driven by low levels of productivity. The acquisition of improved knowledge on the behaviors of individuals at each stage of breeding enables more targeted conservation efforts and reduces the need for additional monitoring visits that may cause increased disturbance and risk of nest failure. We hope that the approach outlined may be developed to provide practitioners who have detailed knowledge of the behavior of their study species with a practical means of assessing the breeding status and outcomes of their study populations.Identifying the breeding status of cryptic bird species has proved problematic without intense or inherently expensive monitoring. Most, if not all, intensive bird monitoring comes with disturbance risks and many projects now rely on tagging of individuals to provide remote information on movements. Given the importance of breeding status when targeting conservation interventions novel methods are needed. This study aimed to identify breeding status in Eurasian Curlew ( Our study has found that it is possible to identify breeding stage of Curlew in terms of incubation, chick rearing or failure from the movement patterns of GPS tagged birds alone. By using frequency plots from a package that normally just determines clustering of points, we can remotely identify the successes and failures of cryptic species that normally wouldn't be possible without intensive and expensive fieldwork. While the causes of species declines can occur throughout a species' life history, maintaining rates of recruitment remains important to ensure stable or increasing populations. Nevertheless, fledging estimates are missing or unknown for many species especially breeding waders  where the precocial nature of their offspring makes monitoring of breeding attempts difficult after incubation  is an iconic breeding species of lowland and upland grasslands and heaths, but which is rapidly declining across many regions in Europe , lesser kestrel , Mediterranean gull , and by Schreven et al. (Anser brachyrhynchus); these studies set the precedent for our study. With respect to waders, tracking studies have specifically been used to distinguish and assess the length of nesting (incubation) attempts in black‐tailed godwit  tags and other tagging sensors  have previously been used to identify the general movements, habitat use, and behavior of a large number of bird species  and overall breeding) can be determined from locational data using a preexisting R package, 22.1Data were collected during a field project based at three locations in North Wales, UK  during the spring breeding seasons of 2016, 2018 and 2019. North Wales contains the majority of the Welsh breeding population of Curlew, with breeding pairs found across a wide variety of habitats from lowland farmed landscapes, e.g., on the Isle of Anglesey, through to upland grassland and heath on the mainland, e.g., in Snowdonia and the Clwydian Ranges . Tags were on average 4.82 g in weight  and were fitted with a small piece of gauze to aid attachment. Following the methods of Seward et al.  were caught by cannon‐netting at the start of the breeding season, between 9th April and 16th May, generally prior to the start of incubation. Each bird caught was fitted with a numbered metal ring and unique combination of color rings for subsequent field identification, and morphometric measurements were taken . Sexes were determined based on bill length and weight , which were downloaded to nearby base stations whenever the birds were in range throughout the tagging period. In total, analyzable data were obtained for 23 individuals  and then imported into R  for a set of relocations  within a predefined radius which for this analysis was set at 20 m  or even 3 days of data (~288) to enable the date of transition between statuses to be identified.The package was initially used simply to identify coordinates of potential nesting locations. However, we then used the “2.2.1Stage 1: Weekly frequency plots: Histograms of revisitation frequency were plotted for each week of the year for which data were obtained for a male Curlew (tag ID 339O_OW) whose breeding status was known through field observations throughout the 2018 breeding season to visually define the distributions associated with breeding status. It was predicted that during incubation bird's activities would be more concentrated with repeated visits to a number of locations, most especially in and around the nest location. Both male and female Curlew share incubation duties , and overall breeding attempts. This 3‐day window was identified as the minimum set of data needed to clearly identify change in breeding status for our 15 min relocations. Incubation and chick‐rearing periods were expected to be ~28 and ~35 days, respectively . However, many studies only use hourly data or less when investigating migration and others only use short bursts of data  and 43.3 days of data (range 0.3–96.1 days) between April and August  on June 13, 2018, the field that the chicks was known to use with their parent was mown and following this the male Curlew showed behavioral signs of chick loss. Attempts to find the nest cup following this were successful, but the temperature logger was not recovered.3.2.1The frequency plots for weeks 19–22 Figure  are bimo3.2.2getRecursions function was run over the smallest subset of data possible without error which proved to be 3 days (~288 relocations). By focussing on those weeks where change occurred, with a rolling 3 day window of data, we identified the specific timing of change based on plots of timed locational data . Two of these birds were either still chick guarding when their tags came off or they moved out of the study site. One bird lost its chicks and is the individual used for the training analysis. The other bird (002O_GO) was observed with chicks in the third week of June 2019, providing validation of the predicted status of this individual. Post‐breeding season sightings of large chicks suggested some of the birds whose tags fell off earlier in incubation may have also successfully raised fledglings.One of the birds that successfully hatched chicks was tagged before it settled and started incubating and we observed 33 days of incubation behavior before we identified the chicks as hatching. Prebreeding behavior was observed in 13 of the 23 birds and post‐breeding behavior in nine. For birds with an observed start date of incubation that failed, we measured an average of 7.0 days (11 birds) before failure for incubation 1 and 7.3 days for incubation 2 (three birds).The presumed (first and second) nest locations of two birds tagged together in 2019 on Anglesey  were identical, and it was thus assumed that these birds were a pair.Based on the 25 predicted nesting (incubation) attempts and their fates, we estimated a daily nest survival rate over the incubation period of 0.935  and a point estimate of nesting success over the entire incubation period of 15.1%.3.4Frequency plots for male ID 339O_OW for 4 weeks of particular interest based on (a) the full data set collected at 15 min sampling intervals and reduced samples taken at (b) 30 min intervals, (c) 60 min intervals, and from (d) daylight mornings (08:00–13:59 UTC) are shown in Figure The plots show that it was progressively less easy to detect reliable patterns in the data as sample sizes were reduced. Data sampled at 30‐min intervals showed similar patterns to the full data set collected at 15 min intervals. However, it was not possible to discern chick‐guarding behavior with data sampled at 60‐min intervals, while no detected patterns were apparent in data sampled from the morning.With the full data set collected at 15 min sampling intervals, dates of change in breeding were visible with a minimum of 3 days of data. However, with data sampled at 30 and 60 min intervals, 6 and 9 days of data were needed, respectively. With data only sampled from the morning, 10 days of data were needed to detect patterns. While it was less easy to discern changes in breeding status when the data set was reduced in size and resolution, it was still possible to identify focal locations based on weekly data. Figure 4recurse  success of Curlew in the present study, limited the information available during the chick‐guarding stage. Thus, use of the approach at other study sites would be particularly valuable in validating predictions during this breeding stage.The approach used in this study, utilizing a preexisting statistical package , it is also possible to then assess how habitat use and requirements may change across the breeding cycle, enabling conservation management interventions to be better targeted. The composition of habitat in breeding areas is highly associated with nesting success in Curlew . Standard monitoring guidelines for upland waders ; formal analysis (lead); methodology (lead); validation (lead); writing – original draft (lead). Stephen Dodd: Resources ; writing – original draft (supporting); writing – review and editing . Patrick Lindley: Funding acquisition (lead); writing – review and editing . Niall H.K. Burton: Funding acquisition (supporting); writing – original draft (supporting); writing – review and editing . Rachel C Taylor: Conceptualization ; formal analysis (supporting); funding acquisition (supporting); methodology (supporting); resources ; supervision (lead); writing – original draft (supporting); writing – review and editing .The authors declare that there are no conflicts of interest.


Dear Editor,1The molecular characterization of glioma genes is essential for properly managing and treating this heterogeneous disease.The study flow chart for this study is shown in Figure We compared TISF at disease progression with paired primary tumour samples in 33 patients Figure , and furIn the cohort of 20 patients (time from patients’ postoperative period to imaging suggestive of progressive disease (PD), shown in Figure We grouped the 20 patients described earlier according to their different mutational statuses in GNAS/CIC at PD. We found that the clinical prognosis of the patients differed significantly between the different groups. Median progression‐free survival was significantly lower in GNAS/CIC‐cleared patients than patients who acquired or maintained the GNAS/CIC mutation at PD. Furthermore, under treatment pressure, patients with GNAS wild type from BL to PD had a better prognosis compared to patients with GNAS clearance. At the same time, there was no significant difference in prognosis compared to patients who acquired or still maintained the GNAS mutation Figure . NotablyAfter disease progression, further analysis of the TISF genome may reveal mechanisms related to bevacizumab's therapeutic effects and drug resistance Figure . New genIn this study, longitudinal analysis of gliomas genomic changes provides more conclusive evidence supporting ctDNA sequencing in TISF to capture the mutational gene profile in gliomas dynamically. What is more, we have revealed through serial ctDNA analysis that gliomas have a high degree of temporal heterogeneity in their true in vivo evolution under standard therapeutic pressure and have identified significant differences in survival prognosis for patients with altered mutational status in genes like GNAS and CIC, which can be used as biological markers to provide early and accurate molecular risk stratification. Changes in ctDNA‐related level indicators such as MVAF and the number of mutations can indicate intra‐tumour heterogeneityThe authors declare no potential conflicts of interest.Supporting InformationClick here for additional data file.Supporting InformationClick here for additional data file.Supporting InformationClick here for additional data file.Supporting InformationClick here for additional data file.Figure S1 Flow chart of study design and patient screeningFigure S2 Genetic characterization of primary tumor tissue in 33 patients and time from postoperative to imaging suggestive of disease progression (PD) in 20 patients.Figure S3 (A and B) The heat map compares the VAF of high‐frequency‐mutated genes in TISF samples at disease progression in Patient 1 and Patient 15, respectively, with the VAF of the corresponding loci in recurrent tumour tissue samples from recurrent secondary surgery.Figure S4 ctDNA changes in TISF and tumour tissue suggest two patterns of tumour recurrence evolution.Click here for additional data file.Table S1 Clinical characteristics of 33 patients with glioma at disease progressionClick here for additional data file.


Medical errors pose high risks to patients. Several organizational factors may impact the high rate of medical errors in complex and dynamic healthcare systems. However, limited research is available regarding probabilistic interdependencies between the organizational factors and patient safety errors. To explore this, we adopt a data‐driven Bayesian Belief Network (BBN) model to represent a class of probabilistic models, using the hospital‐level aggregate survey data from U.K. hospitals. Leveraging the use of probabilistic dependence models and visual features in the BBN model, the results shed new light on relationships existing among eight organizational factors and patient safety errors. With the high prediction capability, the data‐driven approach results suggest that “health and well‐being” and “bullying and harassment in the work environment” are the two leading factors influencing the number of reported errors and near misses affecting patient safety. This study provides significant insights to understand organizational factors’ role and their relative importance in supporting decision‐making and safety improvements. Since the U.S. Institute of Medicine (IoM) published their pioneer safety report, which shows up to 98,000 people dying as a consequence of preventable medical errors  model to help explore organizational factors that may influence patient safety. Being at the intersection between statistics and machine learning, a BBN model represents either causal probabilistic relationships or statistical dependencies among interconnected variables. Further, when BBN features are exploited, the analysis goes beyond basic data analysis and potentially reveals deeper insights, probabilistic outcomes, and valuable findings.Identifying organizational factors that contribute to patient safety errors is vital toward knowing how to provide sustainable safety improvements. The primary purpose of this article is to evaluate the relationship between organizational factors and reported error rates related to patient safety and establish the relative importance of the factors through the lens of BBNs. In this study, our intention is not to test specific hypotheses, but rather to explore organizational factors and their probabilistic dependencies on the safety outcome.The outline of the paper is as follows: The literature review on organizational factors and patient safety, and BBNs is presented in Section 22.1Various factors may play a role in the occurrence of incidents in different industries and domains  health and well‐being; (X3) immediate managers; (X4) quality of care; (X5) safety culture; (X6) team working; (X7) safe environment—bullying and harassment (b&h); and (X8) safe environment—violence. Within these factors, there are 32 specific survey items. Table Our data source is the British NHS staff survey data. With the availability of the data, we analyzed the following eight factors in the survey that could be related to patient safety: (X1) equality, diversity, and inclusion (X1) has been fed by four questions (see Table q16b). The calculation of this outcome measure is based on the percentage of staff selecting “yes” out of those who responded to the question from the respective hospital. It should be noted that a higher score provides a more favorable result for organizational factors, while it is the opposite for the target variable (patient safety errors).As shown in the unit/remarks column in Table It should be noted that hospitals may have different characteristics; therefore, hospital‐level comparison may be limited in prediction and feature importance analyses. However, to prevent such issues, the survey data have primarily been weighted by NHS considering the occupational group weight, trust size weight, and the combination of these two weights NHS SCC, . The weiTable As shown in Table p‐values. Results showed that the relationships between each organizational factor and patient safety errors are statistically significant ) attached to each variable Xi with parents pa(Xi). For instance, if there is an arc leading from each of X2, X7, and X8  to X9 (target variable), X2, X7, and X8 are classified as the parents of X9.a conditional probability table As discussed earlier, we adopt a data‐driven BBN model to investigate the probabilistic dependencies between the organizational factors and patient safety errors. A BBN model comprises the following elements:U=X1,…,X9, factoring joint probabilities are obtained through the chain rule of probability theory resulting from the calculations conducted under certain probability states. The value of a particular node is conditional solely on its parent nodes’ values in the BBN model. Thus, the unique joint probability distribution, P(U) represents the product of all conditional probability tables with the given Equation  Backward propagation of beliefs once the low state of patient safety errors is established. (b) Probability distribution of factors associated with patent safety errors. (c) Backward propagation of beliefs once the high state of patient safety errors is established.health and well‐being” and “safe environment—bullying and harassment” are the two leading critical factors in the back propagation impact assessment given the low and high state of patient safety errors.The impact assessment across the organizational factors given the low and high state of patient safety errors is summarized in Fig. Safe environment—bullying and harassment” was identified as the most critical factor relative to its adverse impact on the target variable since it yielded the highest net increase in the probability (35%) associated with patient safety errors  associated with patient safety errors  of a factor represents its impact on a target variable associated with the realization of the worst (best) possible state of the factor  health and well‐being; (X3) immediate managers; (X4) quality of care; (X5) safety culture; (X6) team working, (X7) safe environment—bullying and harassment; and (X8) safe environment—violence, have a statistically significant relationship with the patient safety errors. These factors were then fed into the BBN model to explore their interdependencies and relative importance towards patient safety errors. Based on the results, our model concludes that health and well‐being (X2), and bullying and harassment in the work environment (X7) are the two leading factors driving the number of reported errors and near misses affecting patient safety.Several organizational factors may have an impact on patient safety errors. Using the survey data, our results revealed that the organizational factors, including (X1) health and well‐being factor and patient safety errors that we found in this study. Therefore, it can be recommended that increased psychological and emotional support to the provider may lead to improved patient safety.In the literature, these factors have been identified as contributing factors to the safety risks in various industries, including healthcare. Specifically, work‐related stress  is a trending topic that its role on patient and provider safety has been investigated widely in various healthcare settings  evaluating organizational factors and their influence on patient safety errors; and (2) adopting a data‐driven BBN approach to provide significant insights on the relative importance of the factors. To our knowledge, this is the first study evaluating a BBN‐based approach in this particular safety context. Identifying the importance of organizational factors is essential for organizations to drive safety improvement. In this study, it is important to note that the data‐driven BBN model has revealed some valuable insights regarding the factors’ relative importance, a central area of uncertainty in risk assessment Aven, . As earlFurther, it is noteworthy to mention that the relative importance of individual factors was established through change assessment in the probability distribution of patient safety errors regarding the realization of individual factors’ extreme states. In terms of the prediction capability, the chosen PC algorithm achieved a classification accuracy of 78% in a three‐state discretization scheme. Our findings revealed that healthcare organizations should improve organizational factors that their providers experience in the work environment to accelerate patient safety improvement. It is, nonetheless, important for not only organizations but also policymakers, such as governments, to support the important factors’ development with appropriate policy implementations , and bullying and harassment in the work environment (X7) are the leading factors driving safety errors. Future studies may benefit from using the same methodology in a specific healthcare unit or organization. Future research may also evaluate and integrate other traditional or machine learning approaches to compare prediction capabilities and possible disparities in the relative importance of the organizational factors. It would also be interesting to collect data not only from providers but also from patients to investigate how patient experience is related to safety outcomes.Utilizing the hospital‐level aggregate survey data from the U.K. hospitals, adoption of the BBN model revealed that Our study has some limitations that may give a caution to interpret and generalize the results. First, this study is based on the hospital‐level aggregate data; therefore, specific units and hospitals may have differences in the relative importance ranking of the organizational factors. Second, the study is based on the data from the U.K. hospitals; therefore, the generalizability and transferability of the results to other industries and countries may be limited. Therefore, future research might also consider replicating this study in different healthcare settings or industries to help create a more holistic conclusion regarding the interdependencies between organizational factors and safety errors.


Please view the corrected table here.There is a typographical error in S1 TableThis parameter set was obtained by a qualitative comparison of the Wilson-Cowan model’s harmonic and temporal spectra with empirical data, and used to illustrate how graph properties affect neural field dynamics in one dimension.(PDF)Click here for additional data file.


Successful conservation and management of marine top predators rely on detailed documentation of spatiotemporal behavior. For cetacean species, this information is key to defining stocks, habitat use, and mitigating harmful interactions. Research focused on this goal is employing methodologies such as visual observations, tag data, and passive acoustic monitoring (PAM) data. However, many studies are temporally limited or focus on only one or few species. In this study, we make use of an existing long‐term (2009–2019), labeled PAM data set to examine spatiotemporal patterning of at least 10 odontocete  species in the Hawaiian Islands using compositional analyses and modeling techniques. Species composition differs among considered sites, and this difference is robust to seasonal movement patterns. Temporally, hour of day was the most significant predictor of detection across species and sites, followed by season, though patterns differed among species. We describe long‐term trends in species detection at one site and note that they are markedly similar for many species. These trends may be related to long‐term, underlying oceanographic cycles that will be the focus of future study. We demonstrate the variability of temporal patterns even at relatively close sites, which may imply that wide‐ranging models of species presence are missing key fine‐scale movement patterns. Documented seasonal differences in detection also highlights the importance of considering season in survey design both regionally and elsewhere. We emphasize the utility of long‐term, continuous monitoring in highlighting temporal patterns that may relate to underlying climatic states and help us predict responses to climate change. We conclude that long‐term PAM records are a valuable resource for documenting spatiotemporal patterns and can contribute many insights into the lives of top predators, even in highly studied regions such as the Hawaiian Islands. In this study, we make use of an existing long‐term, labeled PAM data set to examine spatiotemporal patterning of at least 10 odontocete  species in the Hawaiian Islands using compositional analyses and modeling techniques. We demonstrate the variability of temporal patterns even at relatively close sites, which may imply that wide‐ranging models of species presence are missing key fine‐scale movement patterns. Detailed spatial information about species presence often aids in the definition of new or distinct populations as well as the understanding of habitat use and movement patterns , rough‐toothed dolphin (Steno bredanensis), short‐finned pilot whale , Blainville's beaked whale (Mesoplodon densirostris), and Cuvier's beaked whale (Ziphius cavirostris). Additional genus or group‐level labels were stenellid dolphins , striped dolphin , and spinner dolphin (S. longirostris)), Kogia spp. ), but potentially containing detections of pygmy sperm whale (K. breviceps) based on sighting records , and melon‐headed whale . However, descriptions of patterns within these labeled data, and comparisons to literature have not been completed.A PAM data set from the Hawaiian archipelago presents a unique opportunity to examine odontocete fine‐scale temporal patterns at several sites over a longer time frame (2009–2019) than most other studies. These recordings include data from two subsites at a remote island in the Northwestern Hawaiian Islands , where records of odontocete spatiotemporal trends are limited compared to the Main Hawaiian Islands. A recent study that applied a machine learning toolkit to this data set resulted in labeled data for eight groupings of odontocetes , temporal analyses and documentation of patterns are relatively novel, as few previous studies have had sufficient detections of these species to describe patterns. In the case of rough‐toothed dolphin, description of spatiotemporal trends based on a novel click type described by Ziegenhorn et al.  were derived from the existing, labeled PAM data set to examine spatiotemporal patterning in the Hawaiian Islands for the eight groupings of odontocetes mentioned above. Composition among sites was evaluated, and significance of temporal patterns was determined using generalized additive models (GAMs) with generalized estimating equations (GEEs). Significant temporal patterns were described and compared to available previous literature. The patterns described improve upon previous research for many species where records at various scales  are lacking, providing a baseline for studies of behavior. The breadth of results presented here highlights the utility of long‐term, fine‐scale detection data in species monitoring efforts.22.1Passive acoustic data were collected in the Hawaiian Islands using High Frequency Acoustic Recording Packages . Further detail on network precision and accuracy can be found in Ziegenhorn et al.  to approximate the number of “true” clicks in that bin. Bins were retained for timeseries only if they had more than a certain number of “true” clicks  terms were removed before creation of the final model. Term order in the final model was determined through backwards selection, based on comparing QICs from models with each term removed sequentially to evaluate their relative contribution to the model's predictive power. p‐value, degrees of freedom, and chi‐squared values from an ANOVA of final models were noted.Generalized additive models (GAMs) with generalized estimating equations (GEEs) were used as a model framework to additionally combat the autocorrelation expected in continuous passive acoustic data sets  were also evaluated for this final model using r2_tjur in the performance package in R, as typically used for generalized linear models with binary outcomes , short‐finned pilot whales (62%), and Blainville's beaked whales .Temporal patterns were modeled with GAM‐GEEs using hourly presence or absence of all types as response variable and hour of day, Julian day , and year (Hawai'i only) as explanatory variables. This provided information on the significance of these temporal scales to detection of species or types Table . ReliablR2 values, nor was there a relationship between more detection hours and better model performance. Model results are discussed in further detail below. Full timeseries of detections for each species and site can be found in Figures Performance of models was variable, with several models (5 of 22) reaching >90% of values within the error bounds of the binned residuals plot, though no model reached >95% Table . These v3.3.1Kogia spp., detections increased during daylight hours. Probability of false killer whale detection was higher during mid‐morning at Kaua'i , with a strong diel trend only at Hawai'i. For rough‐toothed dolphins, the bottlenose dolphin and melon‐headed whale class, short‐finned pilot whales, and stenellids, models showed a distinct diel trend, with echolocation detections being much lower in daylight hours  sightings also match our findings, in which detections were more common off Hawai'i than off Kaua'i , manual review was completed for all false killer whale detections, and this manually modified data set was used moving forward  among species may have led to some variation in detectability in this data set. However, considering acoustic presence on a relatively coarse scale compared to the scale of cue rate variability should have mitigated such issues. Species‐specific thresholds for “true” detections also served to minimize differences caused by cue rate. Additionally, it is worth noting that the species considered produce a variety of other vocalizations that were not included in this study. Incorporation of these vocalizations  would further contribute to fully describing acoustic presence patterns of the species considered.Feresa attenuata, in our data set due to a resident population off the coast of Hawai'i  have been noted in very few previous studies. Research on the Main Hawaiian Islands insular stock of false killer whales found some spatial variability in use of the Main Hawaiian Islands region for one social cluster of animals, with highest presence west of Hawai'i during spring and early summer (May through July) and west of Kaua'i in summer and early fall . One downside of including year as a smoothed term in this model is that the representative figures necessarily indicate relationships during years where there is little to no data . It is not possible to say whether the true relationship during those years would be similar to what the model suggests, so we refrained from drawing conclusions related to those time periods. Changes in presence may also be linked to oceanographic variables, particularly those that affect the presence of various prey species. The dip in presence in 2018 is particularly interesting as there was continuous effort throughout that year. Future work on this data set using environmental correlates may illuminate the reasons for this decrease in detections.Multiyear analysis at Hawai'i yielded interesting results in several cases, though in most cases these patterns had no comparable records in the literature. A distinct peak in presence in 2010 was observed for rough‐toothed dolphins, short‐finned pilot whales, and Blainville's and Cuvier's beaked whales. In 2014, a dip in presence was observed for many types. Presence then peaked again in 2016 for all types except false killer whale and 5Kogia spp.). The work presented here highlights the utility of using multiple methodologies for studying species in this region and others.Discussion of various temporal predictors in relation to previous studies highlights the importance of continued monitoring efforts, in this region and others, to inform understanding of odontocete spatiotemporal patterns. This is especially true for species where this study presents the first regional description of a given pattern, or previous records are not comparable to the effort of the PAM data set used  where the records provided here have little to no comparison in previous literature. In that way, this study provides a useful starting point for other species‐specific studies of these animals. Future work employing these results in models considering environmental and anthropogenic parameters will help provide explanations for the patterns observed. These will be useful in the further understanding of these species habitats and behaviors and may help to explain any existing behavioral discrepancies between this and previous studies. These behaviors and movements are important to understand in the context of the Hawaiian ecosystem to which these odontocetes belong. The work completed emphasizes the merits of establishing baselines and comparing patterns of detections on fine temporal and spatial scales in marine top predator monitoring efforts. The patterns established in this study provide useful records to which additional studies of included species can be compared, allowing for documentation of regional differences in temporal behaviors which may be relevant for conservation purposes. These processes are necessary for management and conservation efforts of these species regionally as well as worldwide.In terms of multiyear trends, results of this study at Hawai'i are novel for most species, though it is worth noting that, as the detection range covered by the HARPs is relatively small (2–5 km for most odontocetes), shifts in acoustic presence may represent small shifts in high‐use areas by island‐associated populations. In Hawai'i, few long‐term trends have been described, though portions of this data set have been used for long‐term assessments of sperm whales ; data processing and analysis (lead); metholodolgy (lead); validation (lead); visualization (lead); writing – original draft (lead); writing – review and editing (lead). John A. Hildebrand: Conceptualization (supporting); methodology (supporting); resources ; supervision ; writing – original draft (supporting); writing – review and editing (supporting). Erin M. Oleson: Data collection (lead); methodology (supporting); funding acquisition ; resources ; validation ; writing – review and editing (supporting). Robin W. Baird: Methodology (supporting); validation ; resources (supporting); writing – review and editing (supporting); Sean M. Wiggins: Resources ; writing – review and editing (supporting). Simone Baumann‐Pickering: Conceptualization (supporting); methodology (supporting); resources ; funding acquisition ; writing – original draft (supporting); writing – review and editing (supporting).The authors have no conflicts of interest to report.Appendix S1.Click here for additional data file.


To provide the first estimates of the risk of suicide after bereavement by the suicide of any first‐degree relative and the proportion of suicides in Denmark attributable to suicide bereavement.n = 32,248), age‐matched to four living controls. Using three exposure categories  and conditional logistic regression adjusted for pre‐specified covariates we estimated the odds of exposure to suicide bereavement in cases versus controls. We tested whether associations differed for men and women, estimated the population attributable fraction (PAF) of suicides in our population at risk that could be attributed to a first‐degree relative's suicide loss, and estimated the attributable fraction among the exposed (AFe).We conducted a nationwide nested case–control study defining cases as all Danish‐born individuals who died by suicide in Denmark between 01 January 1980 and 31 December 2016  or non‐suicide bereavement . There was no evidence to support any interaction with sex. PAF  and AFe  estimates suggested that in Denmark 0.69% of suicides, and 60% of suicides among suicide‐bereaved relatives, could be prevented if it was possible to address all factors increasing suicide risk in suicide‐bereaved relatives.Suicide bereavement was associated with an increased odds of suicide when compared with no bereavement (ORSuicide bereavement in relatives and partners contributes to at least one in 145 suicides in Denmark. Risk of suicide is elevated in relatives and partners bereaved by suicide, whether compared with people bereaved by other causes or people unexposed to bereavement.An estimated one in 145 suicides in Denmark is attributable to the suicide loss of a first‐degree relative.If we could eliminate exposure to suicide bereavement (or address factors increasing suicide risk in Danish people bereaved by a relative or partner's suicide), we could prevent an estimated 60% of suicides in this group.Our exposure classification under‐ascertained bereavements recorded i) prior to 1980, ii) overseas, iii) of relatives not identified by linkage prior to 1953, or iv) where individuals had been exposed to both suicide bereavements and other bereavements.Our analyses underestimated psychopathology because of the lack of data on primary care presentations and outpatient care, as well as episodes of mental illness or self‐harm in which no healthcare presentations were made.1Suicide bereavement is estimated to affect 22% of the population across the life course and 4% of the population in any given year.Systematic reviews of this literature show that the risk of suicide after suicide loss has only been quantified in specific kinship groups bereaved by suicide.1.1To use Danish population‐based registry data to estimate the association between bereavement by the suicide of any identified first‐degree relative  and risk of suicide in relation to two reference groups: (a) people bereaved by other causes of death (controlling for the trauma of bereavement per se) and (b) people not bereaved by any identified first‐degree relative's death.To assess whether the relationship differed for men and women.To estimate the proportion of suicides attributable to suicide bereavement in the population (PAF) and among those exposed (AFe).22.1We conducted a population‐based nested case–control study (case–control within a cohort study) to quantify the risk of suicide after exposure to a relative's suicide, whether related genetically (parents/children/siblings), by adoption, or partnership (spouse/civil partner/cohabiting partner), with no age restrictions. Cases were defined as people who had died by suicide (our outcome), controls were age‐matched individuals alive on the day of suicide, and our exposure of interest was prior death of a linked first‐degree relative since 1980.2.2An individual‐level data linkage on all Danish‐born residents who had not migrated since birth was conducted using a unique personal identification numberUsing incidence density sampling,2.32.3.1Exposure was classified according to bereavement by the death of a parent, child, sibling, partner or former partner between 01 January 1980 and 31 December 2016 that occurred prior to the suicide of the case (or corresponding matching date among controls), using relevant ICD‐8 and ICD‐10 codes Table . We defi2.3.2Seven confounders were identified a priori based on the literature, identifying pre‐bereavement differences on physical and mental health measures between people bereaved by suicide and bereaved or non‐bereaved controls.Marital status was used as distinct from cohabitation status to capture the confounding effect of divorce.All covariates were updated on the exact date of change  or  January 1 each calendar year. Within each set of one case and four controls we measured values for each time‐varying covariate at the same timepoint, based on the earliest date of exposure within each set. For individuals who had experienced multiple bereavements, covariates were measured for the first bereavement. For sets in which no‐one was exposed, we assigned a pseudo index date2.4We conducted our main analyses on cases (who had died by suicide) and living age‐matched controls who had complete data on all variables in the analysis, comparing their exposure to suicide bereavement, other bereavement, and no bereavement. As both cases and exposures were defined according to a suicide, any individual who died by suicide between 1980 and 2016 was classified as a case, but would also have defined their relatives as exposed to suicide bereavement. The demographic and clinical characteristics of cases and controls were examined using frequencies/percentages  or medians/interquartile range (continuous variables). We estimated the association between suicide bereavement (exposure) and odds of suicide using conditional logistic regression, with each case forming a separate stratum. As controls were randomly selected from the appropriate risk sets, estimated odds ratios were indicative of unbiased estimates of the corresponding incidence rate ratios from the wider cohort.Initially, we estimated the univariable association between bereavement status and suicide, changing the reference category to compare suicide bereavement with (a) other bereavement and then (b) no bereavement. We re‐ran models adjusted for potential confounders . We used Wald tests to assess effect modification by sex within each model including an interaction term between bereavement and sex.punafcc command in Stata.We estimated the PAF and AFe for our univariable and multivariable models, with 95% confidence intervals, using the user‐written To establish whether missing data were associated with suicide bereavement (exposure) and/or with suicide (outcome), we compared characteristics between the analytic sample and those excluded because of missing information. A proportion of data were missing because income and marital status data were only available from 1980, therefore pre‐bereavement income and marital status were unavailable for some individuals who were bereaved early on in the follow‐up period.We carried out a sensitivity analysis to estimate associations using multiply imputed data, assuming data were missing at random. We performed multiple imputation by chained equations based on 50 iterations, including all confounding variables, exposure, and outcome. To account for the matched design, we included the matching variable (birth year) within our imputation model.Data preparation was carried out in SAS software version 9.4.3N = 161,240), there were 12,981  with missing information on income or marital status. Given the matched design, this excluded 14,086 (8.7%) individuals. These individuals were older and more likely to be female, widowed, and to have a history of depression, or any physical disorder  with complete data consisted of 29,513 cases who died by suicide and 117,641 living age‐matched controls  than non‐suicide bereavement .Suicide bereavement was associated with increased odds of suicide compared with exposure to other bereavement and with no bereavement Table . In unadp = 0.107), or non‐suicide bereavement (p = 0.896)Table .Our PAF estimate, based on the fully adjusted model, suggested that approximately 0.69% (95%CI: 0.62%–0.77%) of suicides could be prevented in the Danish‐born population of Denmark if no first‐degree relatives experienced suicide bereavement, assuming a causal association Table . The corOur findings were robust to a sensitivity analysis based on the multiply imputed sample Tables  and S4.44.1We found, in our nested case–control study of the whole Danish population, an elevated risk of suicide in relatives and partners bereaved by suicide, whether compared with people bereaved by other causes or people unexposed to bereavement. This is the first study to have quantified the suicide risk associated with suicide bereavement for all first‐degree relatives (including partners), complementing previous studies presenting risk estimates for individual kinship groups.Our hypothesis was supported that the magnitude of risk associated with suicide bereavement was greater when compared with unexposed controls than bereaved controls, in keeping with our broader understanding of the impact of suicide bereavement relative to other losses.4.2No other studies investigating the effects of suicide bereavement have calculated PAF/AFe estimates, and few examples are provided in the research literature for other suicide risk factors. We are therefore limited in the comparisons we can make to those calculated for other risk factors, such as sexual abuse or PTSD, although our estimate remains much lower than these. Our estimate of the magnitude of suicide risk associated with suicide bereavement across a range of kinship groups complements evidence from registry‐based studies describing an elevated risk of suicide in individual kinship groups; after the suicide of an adult child,4.3Providing the first estimate of suicide risk associated with suicide bereavement for all first‐degree relatives, including partners, was possible using a case–control design and data on an entire population at risk.The nested case–control design, matching cases and controls on birth year, partially dealt with the problems encountered using a cohort study design in addressing heterogeneity of kinship groups and age at loss . Our use of routine registry data addressed problems of recall bias typical of cross‐sectional data, and meant we had low levels of missing data and for only two key variables . Our exclusion of some (8.7%) cases and controls from the analysis because of missing data may have biased our findings based on their characteristics. However, our findings were robust to investigation of the effects of potential biases introduced by missing data. Our exposure classification under‐ascertained bereavements recorded prior to 1980, overseas, of relatives not identified by linkage prior to 1953, or where individuals had been exposed to both suicide bereavements and other bereavements. We did not take into account multiple exposures (of the same or another bereavement type) because we wanted to investigate the specific impact of suicide loss, and this was not a clear confounder. Our use of a household variable to capture cohabitees as well as legally‐recognised partnerships addressed under‐ascertainment of partner bereavement, but the standard partner definition excluded same‐sex cohabitees and couples with larger age differences.Our use of variables from a range of linked population registers meant we were able to adjust not only for pre‐bereavement psychopathology, but also other important potential sociodemographic and clinical confounders. This improves on previous registry‐based analyses taking into account only age, sex, time since loss and kinship.4.4These findings confirm to clinicians and policymakers that bereavement by the suicide of a first‐degree relative, including former/current partners, is a risk factor for suicide, supporting its inclusion in suicide prevention strategies as a focus for intervention (termed postvention).Our PAF and AFe estimates are useful tools for policymakers in considering the relative contribution of suicide bereavement among suicide risk factors. Such figures are illustrative, assuming causality , and set out the challenge that if we could prevent suicide bereavement (or address the mediators of suicide risk in suicide‐bereaved relatives), we could prevent 0.69% of suicides in this population. Suicide bereavement is theoretically a modifiable exposure through wider efforts to prevent suicide. However, given these challenges, it may also be possible to reduce the incidence of suicide in the suicide‐bereaved by addressing  modifiable mediators of the association between suicide bereavement and suicide. As these mediators have not yet been identified, it is assumed that this could be achieved through investment in a broad range of bereavement support services to address the unmet needs of the suicide‐bereaved.5In conclusion, these first estimates of the population burden of suicide mortality after suicide bereavement of a first‐degree relative, and the burden specific to the suicide‐bereaved, highlight the importance of reducing exposure to suicide and addressing the known adverse effects of suicide bereavement in care planning as part of global efforts to reduce suicide mortality.The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.https://publons.com/publon/10.1111/acps.13493.The peer review history for this article is available at The study was approved by the Danish Data Protection Agency and informed consent was waived. Institutional approval to analyse extracted data was provided by the UCL Research Ethics Committee .Appendix S1 Supporting Information.Click here for additional data file.


Anolis lizards was one ornament previously thought to conform to the classical expectation of hyper‐allometry. We re‐evaluated this classic example alongside a second arboreal group of lizards that has also independently evolved a functionally equivalent dewlap, the Southeast Asian Draco lizards. Across multiple closely related species in both genera, the Anolis and Draco dewlaps were either isometric or had hypo‐allometric scaling patterns. In the case of the Anolis dewlap, variation in dewlap allometry was predicted by the distance of conspecifics and the light environment in which the dewlap was typically viewed. Signal efficacy, therefore, appears to have driven the evolution of hypo‐allometry in what was originally thought to be a sexually selected ornament with hyper‐allometry. Our findings suggest that other elaborate morphological structures used in social communication might similarly exhibit isometric or hypo‐allometric scaling patterns because of environmental constraints on signal detection.Visual ornaments have long been assumed to evolve hyper‐allometry as an outcome of sexual selection. Yet growing evidence suggests many sexually selected morphologies can exhibit other scaling patterns with body size, including hypo‐allometry. The large conspicuous throat fan, or dewlap, of arboreal Caribbean  The large conspicuous dewlap of anoles and other lizards that were previously thought to be hyper‐allometric and the product of sexual selection are in fact isometric or hypo‐allometric and the product of signal detection. When these structures honestly reflect individual condition, the size of ornaments or weapons can operate as a condition‐dependent signal that receivers can use to assess the relative quality or fighting potential of its owner  termed ‘hyper‐allometry’. This is because larger individuals are able to invest more in exaggerated sexual characteristics than smaller individuals, resulting in a disproportionate increase in the size of ornaments or weapons with increasing body size across males within the population. Furthermore, the magnitude that exponents exceed 1  has been argued to reflect the extent to which the exaggerated structure is targeted by sexual selection  from the islands of Puerto Rico and Jamaica. Males use a conspicuous throat fan, or dewlap, as part of a visual display used to establish and maintain territories that encompass several trees , another arboreal genus that are remarkable parallels in behaviour and ecology to the Anolis  for each male lizard to compute within‐taxon static allometries  from 14 taxa  from Puerto Rico and Jamaica, and multiple free‐living territorial males of Draco  from six taxa  from peninsula Malaysia and Borneo. See Tables We studied multiple free‐living territorial males of Males in both genera establish territories that typically comprise several trees or shrubs and frequently advertize territory ownership from arboreal perches using elaborate visual displays. These displays include the extension of a large, often colourful dewlap, with males typically orienting themselves on perches in order to maximize the conspicuousness of displays to a variety of surrounding conspecific receivers  were digitally measured from extracted video stills using software ImageJ v.142q . Lizard body length estimates, SVL, were based on a measure from the snout to the approximated vent position at the base of the tail. Three measures of dewlap area and SVL were taken from three separate bouts of display for each male lizard (repeatability estimates across the three measures are provided in Tables Draco) and body length. Averaging was done to control for potential measurement error. In the case of dewlap area, this ‘average’ still represented the size of the dewlap at its maximum extension (not its average extension length).From the archive library of video recordings, we exported still images during periods where males had their dewlap fully extended and without the dewlap extended in order to more accurately measure body length. The external anatomy of the Draco lizards developed by Ord, Blazek, et al. . A digital video camcorder mounted on a tripod was positioned several metres away from the displaying robot. A Ping‐Pong ball of known size was video recorded where the robot had been positioned to calibrate the distance of the camcorder from the robot. Stills of the robot with its dewlap at full extension were then extracted from the video, and ImageJ was used to measure both the area of the dewlap and length of the robot body. There was no statistical difference in either dewlap area or the length of the body compared to their known values . Video estimates of dewlap area were on average of 3.6% smaller than known values, but not statistically different from zero with a 95% confidence range of 9.7% smaller to 2.5% bigger than known values. Video estimates of body length were on average of 0.5% longer than known values, but again this was not statistically different from zero with a 95% confidence range of 2.6% shorter to 3.7% longer than known values. These analyses show the measurement of dewlap area and body length from video stills of displaying free‐living lizards provide a reasonable and non‐invasive estimate of these features.To confirm the accuracy of measurements taken from video stills, we used 15 robotic , et al.  to compa, et al. ). These 2.2b). Intercept values were not evaluated as variation among taxa in slope estimates make direct comparisons of intercept estimates difficult, unless body size data is subject to some form of mean centring transformation . Dewlap and lapel area measurements were first linearized using a square‐root transformation  and each species separately, for a total of 14 within‐taxon static allometries for Anolis and six within‐taxon static allometries for Draco. Our previous work on other animals has indicated that estimates of static allometry can be accurately computed when roughly 10 or more individuals have been sampled over a wide range of adult body sizes in a population  or reduced major axis regressions, but a general consensus has begun to emerge that OLS regression provides a more reliable analysis for estimating allometry relationships  were entered into a series of phylogenetic regressions with various combinations of ambient light, visual noise, receiver distance (in the exclusive case of Anolis) and their interactions. These analyses relied on an Ornstein–Uhlenbeck (OU) process to model the residual variation in regressions and were implemented with the package ‘phylolm’ version 2.6.2 . These values were converted into model weights  were calculated using a phylogenetic OU regression of mean‐taxon dewlap area on mean‐taxon body length separately for Anolis and Draco. An additional analysis was also conducted for Draco that used an estimate of dewlap area inclusive of the lapel. Third, in order to evaluate the extent to which habitat accounted for differences in mean area of the dewlap (relative to taxon body length), we applied an additional set of regressions that included various combinations of ambient light, visual noise, receiver distance (in the case of Anolis) and their various interactions. In these analyses, we used the residuals of mean‐taxon dewlap area as a function of mean‐taxon body length computed from the bivariate evolutionary allometry regressions to focus the analyses specifically on mean‐taxon dewlap area controlling for taxon body size. An alternative approach of standardizing dewlap area would be to use the intercept values computed from taxon static allometries in which body size is centred on a common value for all species. This approach is generally not appropriate for our study because there are several species of Anolis and Draco that do not overlap in size range . It is still possible to compute a global mean for all species of a genus and then rely on intercept values that might be inferred beyond the range of the available data for that species. There are statistical concerns with doing this, but we nevertheless repeat the habitat analyses in which residual dewlap areas are substituted with static allometry intercept values where body size has been centred on a global mean. These analyses are reported in Table Our final set of analyses investigated the evolutionary allometry of the dewlap—differences in mean‐taxon dewlap area as a function of mean‐taxon body length—and the extent to which the average size of the dewlap across taxa could be predicted by the type of habitat occupied by species. First, we averaged the natural‐logged transformed data across males within a given taxon to compute the mean size of the dewlap and mean body length of that taxon. Second, evolutionary exponents  of 0.77–0.91, and for male Draco lizards were on average of 0.62, with a 95% CI of 0.51–0.73 . That is, dewlap size in both genera exhibited hypo‐allometries, with larger male lizards possessing disproportionately smaller dewlaps compared to smaller male lizards.No e Figure . InsteadAnolis and Draco taxa in estimated allometric exponents . However, we lacked information on receiver distance for Draco lizards and our sample size was also lower for Draco than Anolis. Furthermore, there was generally little variation in computed exponents across Draco taxa.There was, however, considerable variation among s Figure . In the ce Table . Specifis Figure , whereas3.2Anolis dewlap across taxa  was generally larger than Draco , but there was a high degree of overlap in the range of dewlap sizes between the two groups, particularly when comparing dewlap sizes of Draco that included the area of the lapel . Furthermore, the evolutionary allometric exponent  across Anolis taxa versus 0.92 (95% CIs = 0.65–1.19) across Draco taxa . Similarly, estimates of the evolutionary intercept  and Draco  were comparable, which again implies the dewlap was approximately similar in size between the two genera.The average size of the t Figure  of the mt Figure  indicateAnolis lizards, variation among taxa in the gross (taxon mean) size of the dewlap was negatively correlated with habitat light , possessed larger dewlaps than taxa living in well‐lit environments. In the case of Draco lizards, variation in gross dewlap size could not be convincingly attributed to any environmental variable  occupy bright environments and communicate to conspecifics over short distances and similarly exhibit hypo‐allometries in their dewlap size .More generally, the isometry and hypo‐allometry of the Anolis is highly elastic . In contrast, all previous studies . What tJenssen,  and is cJenssen, . That isJenssen, , 2000. AAnolis dewlap is not evident for Jamaican and Puerto Rican anoles. This is significant because hyper‐allometry has served as evidence for dewlap size being a key target of sexual selection (e.g. Echelle et al., Regardless, what is clear is that the putative hyper‐allometry of the TCS and TJO conceived the project, designed the study and collected the data. TJO funded the work and obtained ethics and licencing approval to conduct the work. TCS analysed the data and prepared the figures and tables. TCS and TJO wrote the paper.The authors have no conflict of interest to declare.https://publons.com/publon/10.1111/jeb.14102.The peer review history for this article is available at Is the author interested in applying for an Open Research Badge?: Yes.Figure S1Click here for additional data file.Figure S2Click here for additional data file.Tables S1–S3Click here for additional data file.


Considering that early detection of squamous cell carcinoma (SCC) improves prognosis and clinical examination is the primary detection method, we identified factors related to the clinical evaluation of oral mucosal lesions. Due to the growing role of telehealth, our study was based on clinical image evaluation.Oral medicine specialists and dental students evaluated six images of benign, potentially malignant, or SCC lesions . We analyzed the role of personal factors of the examiners and the visual pathological features of the lesion upon which the participants based their evaluation.One hundred thirty‐three subjects participated. Half of the benign images were correctly evaluated. On average 1.2 (±SD1.3) cancer pictures were recognized correctly and 3.66 (±SD1.42) images were considered potentially malignant. Potentially malignant lesions were correctly evaluated at an average of 4.08 (±SD1.48) images. For cancer and potentially malignant lesion images, there were significantly better results among clinicians with the worst results from the fourth‐year students. Student results correlated significantly with years of study, number of weeks spent in the oral medicine clinic, and interest in oral pathology. Consideration of lesion irregularity yielded a correct diagnosis, whereas wrong answers were based on color changes. Lesion size and margins were considered equally important.Using clinical images as part of the diagnostic process provides good results, though increased clinical experience for graduates and undergraduates may be necessary to improve accuracy. Therefore, emphasizing the important visual parameters of malignancy may be valuable in the current telehealth era. Therefore, here our first aim was to analyze factors about the examiner associated with the correct evaluation of visual features of oral lesions. The second aim was to investigate image assessment in order to determine which visual factors affect correct evaluation. Our final aim was to use our analysis to suggest ways to improve accuracy of diagnosing lesions based on clinical images.2In order to eliminate bias, participants examined clinical images without any accompanying details and completed a questionnaire.2.1Oral medicine clinicians and dental students at the Hebrew University‐Hadassah School of Dental Medicine, in their final 3 years of study, participated. Participants were invited by email and those consenting to joining the study were sent a link to an anonymous questionnaire associated with clinical images viewed at a screen.2.2Images—In order to minimize variables such as site differences, we focused on the lateral tongue, which has the highest prevalence of SCC. The images used were original, taken at the oral diseases' clinic using a Canon 1200D , using a ring flash. Images were 5–7 MB in size and saved as JPEGs. The pathology, when present, was located in the center of the image and in focus. Images with multiple pathologies, blurred images, and those with too bright a flash were excluded. The benign group included images of normal appearing mucosa from common, benign conditions Figure . The potA pilot study with 24 clinical images showed that the time needed for full completion of the questionnaire was approximately 20 min, with reduced attention at the last images, while 18 images allowed better attention and full compliance. The 18 original clinical images of the lateral tongue were presented in the same randomized order to all participants with no additional information. For each image the participants chose the most probable diagnosis  and were asked to select which two features assisted them the most in their evaluations: size, color, margins, irregularity which refers to nonhomogenous features of the lesion (such as variation in color and warty or verrucous appearance), or lesion surface appearance . We divided the responders into three groups according to their evaluation accuracy. Those evaluating up to eight images correctly (a correct answer rate of less than 50%), those with a correct evaluation of 9–11 images (51%–66%) and those who were correct for 12–18 images (67%–100%). We then investigated whether the degree of evaluation accuracy was related to any of the personal characteristics recorded: age and gender, and for students their year of study, their degree of interest in the field of oral medicine , and the number of mandatory rotations in oral medicine clinic during their undergraduate dental training. For clinicians, the number of years of experience as a clinician was recorded.2.3The work described is in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki) for experiments involving humans. The study was approved by the institutional ethics committee (#30102017). Participation was voluntary, with informed consent.2.4t‐tests or Mann–Whitney tests for nonparametric data were performed to compare quantitative variables between two groups. For comparing quantitative variables between three or more groups, analysis of variance (ANOVA) test or Kruskal–Wallis for nonparametric data were performed. If significance was found, further paired comparisons and Scheffe post hoc analysis was performed. Nonparametric tests were used when one of the groups was small and the distribution was not normal. Normality was tested by Kolmogorov–Smirnov test. In order to determine the correlation between two qualitative variables, Chi‐squared test and Fisher's exact test were used. Furthermore, in order to determine significance of a trend for a qualitative variable the linear‐by‐linear test was used. Statistical significance was set as p < 0.05. Data was analyzed using SPSS‐IBM version 25.Student's 3A total of 133 individuals participated in the study—125 students (94%) and 8 clinicians (6%). There were 50 males (37.6%) and 83 females (62.4%), aged 21–44 years with an average age of 27 years. The distribution of the year of study of the students was approximately equal for each year  or benign (p < 0.001). Post hoc analysis showed that the source of the difference was the fourth‐year students (data not shown).Analysis of the groups evaluating the six images of erythro/leukoplakia with diagnosed dysplasia is presented in Figure 5p < 0.01) or benign (p < 0.01) (ANOVA). Post hoc analysis showed that the responses of the fourth‐year students were the source of this difference (data not shown).Analysis of the groups evaluating the malignancies is presented in Figure 6p < 0.001) even when analyzed by linear‐by‐linear association (p < 0.001). Table p < 0.001) and the trend remained significant when analyzed by linear‐by‐linear association (p < 0.001). Finally, there was a significant trend toward more correct answers  for students who expressed a greater interest in mucosal pathologies  for st7The six SCC images were evaluated by 133 participants and yielded 798 responses. After deleting 11 partial responses, from the remaining 787 we analyzed which features were important to those making the correct evaluation compared to those who were incorrect  lesions. There was no significant difference between the subgroups (clinicians versus students in each year). These results may be due to a high level of suspicion among the participants in a research project, making them evaluate benign images as pathologic. Clinically, a higher level of suspicion is preferable, such that this finding can be considered acceptable.At the other end of the pathological spectrum were the images of SCC of the tongue. The clinicians had the highest number of correct evaluations followed by sixth‐year students, with the fourth‐year students showing the least accuracy. All students were already exposed to the relevant courses covering oral examination and oral potentially malignant disorders, so the differences in accuracy between fourth‐year students and the higher years shows that even a relatively short amount of clinical time improves diagnostic skills. Most SCC images were considered as pathologic and not normal by all participants. While a mistaken evaluation of SCC as potentially malignant lesion is not ideal, it usually means that the correct steps for a diagnosis  will be taken. These findings reflect a clinical dilemma in differentiating between SCC and a potentially malignant lesion, which have nonspecific and overlapping visual features.When dividing the responders into groups based on evaluation accuracy, we found that clinicians had the best results and fourth‐year students had the poorest, following a pattern where the percentage of correct evaluations increased with experience. The relationship between better performance and more rotation weeks indicates that time spent in the oral medicine clinic improves diagnostic skills. Therefore, undergraduate programs should include at least 2 weeks of exposure to “oral medicine”‐like clinics in which nondental pathologies are examined and diagnosed. Indeed, the need for further education is also supported by the findings of others.The next factor we wanted to examine was the amount of interest participants had in oral mucosal pathologies. The trend noted in the current study was more evaluation accuracy with greater interest, with the group reporting the highest interest having the most correct responses and vice versa. The tendency of better results with higher consistency and absolute agreement among oral medicine specialists compared to other dentists evaluating clinical images has been reported previously.Analysis of the results for all the images showed that males had higher percentage of correct answers than females. This finding was not apparent in the analysis of the subgroup of cases. Studies on gender differences in diagnostic ability have yielded inconsistent results.The importance of image evaluation and visual parameters has increased remarkably with the telehealth trend due to the COVID‐19 pandemic. In order to determine which visual features assisted in making a correct evaluation, the participants were asked to identify the main visual feature that affected their decision. The significant differences identified between correct and incorrect evaluations of SCC images were lesion irregularity and color, respectively. While all responders considered the surface appearance as a major parameter, irregularity was the feature that correct responders relied on more than the incorrect responders, suggesting its importance in rendering an accurate evaluation at the time of diagnosis. Although “irregularity” is a nonspecific term providing no clear description of visual features, it is an important feature that can reflect epithelial and subepithelial changes and includes atrophic, hyperplastic, and indurated areas.Although the analysis of diagnostic abilities based on clinical images alone might be limited, this technique has been used previously.Our results are applicable to both clinical and “digital” settings and support the positive attitude of younger clinicians toward this tool for teaching, monitoring premalignancy, and clinician communication.9The clinical primary diagnosis of SCC and potentially malignant disorders improves with experience and interest in mucosal pathologies. Because increasing clinical experience improves diagnostic skills, it would be beneficial to expand clinical exposure during undergraduate training and in continuing education programs. The utilization of clinical images in the process of developing a diagnosis may be a helpful adjunct and provide accurate results when evaluated by properly trained clinicians emphasizing the important visual parameters of malignancy such as lesion irregularity. These findings may be of great value in the currently expanding telehealth era.The authors declare no conflict of interest.