A puzzle has emerged amidst rising inequality: why do people profess high levels of belief in meritocracy even as income gains are increasingly concentrated at the top? In light of contradictory theories and evidence, we undertake the first assessment of the relationship between local income inequality and meritocratic beliefs outside the United States, using data from the UK Household Longitudinal Study. We find that the positive relationship between country‐level income inequality and meritocratic beliefs identified in the recent literature does not translate straightforwardly below country level: there is no robust relationship between local income inequality and meritocratic beliefs in England. However, there is a robust—and somewhat paradoxical—positive association between high local income inequality and meritocratic beliefs among those with the lowest incomes. On average, respondents with annual household incomes of £10,000 are five points more likely  to believe their hard work will pay off if they live in the most rather than the least unequal places in England. We also show that this applies beyond the specific case of meritocratic beliefs: low‐income respondents in unequal places are also notably more satisfied with their own (low) income than similar respondents in more equal localities. In line with system justification theory, we argue that belief in meritocracy serves as an important tool of psychological resilience for low‐income individuals who regularly come into contact with others more economically fortunate than themselves: though it legitimates their current position at the bottom of the status hierarchy, this belief also offers the promise of future advancement. While this reduces concern about the psychological effects of growing local income inequality on the most economically vulnerable, it also suggests that there is little prospect of demand for systemic economic change emerging from what might have been considered the most likely places. Invented as a dystopian satire Young, , the ideThe peculiar relationship between country‐level income inequality and meritocratic beliefs is documented by Mijs , who shoThis explanation raises important questions about the relationship between local contexts and meritocratic beliefs. Though a simple extrapolation of Mijs'  findingsExisting evidence on this topic is contradictory. Exploring the relationship between local income inequality and meritocratic beliefs in the United States, both Newman et al.  and SoltWhile Newman et al. have subsequently acknowledged two sets of errorsThe nature of the relationship between income inequality and meritocratic beliefs is fundamental to the broader questions of how (and how much) income inequality affects individual well‐being  across economic fault lines, with rich and poor increasingly living their lives in separate spheres. The growth of meritocratic ideology reflects the increasing social and spatial distance between income groups and the fact that, as the gap grows larger, other people's lives fade out of view  drawn from the US Religious Landscape Survey (RLS) and reach largely opposite conclusions. They find that low‐income respondents living in the most unequal counties are 19% points (±7) less likely to reject meritocracy than similarly low‐income people living where inequality is at its lowest observed level. Or formulated differently, low‐income respondents tend to express a stronger belief in the meritocracy if they live in high inequality localities. The same shift in local income inequality is associated with a decline in the predicted probability of rejecting meritocracy among individuals with household incomes below $50,000, but there is no relationship above this income threshold. We therefore also test the following counter subhypothesis (H2b): the more unequal the local context in which low income people live, the stronger their belief in meritocracy; for high income people, this association is attenuated.However, the claims of Newman et al.  have nota means of escaping the subjective sense of powerlessness, if not its objective condition  English unitary authorities, metropolitan boroughs, nonmetropolitan districts, and London boroughs  illustrated in Figure English Atlas of Inequality, and experimental admin‐based household income statistics produced by the Office for National Statistics (ONS) for the tax year 2015–2016. Due to LAD‐level data availability, we restrict our analysis to UKHLS respondents based in England. Following this restriction and listwise deletion, the analytical sample comprises 24,943 respondents in 315 Local Authority Districts in England.We match individual‐level location data to administrative data drawn from a range of sources, including the UK Labour Force Survey, Rae and Nyanzu's , 2019b E3.2Our dependent variable is derived from a one‐off question asked in Wave 5 of the UKHLS, when respondents were asked to express their agreement or disagreement with the following statement: “I have always felt like my hard work would pay off in the end.” This question differs from the more general survey items employed as measures of meritocratic beliefs by Mijs , Newman 3.3In line with the great majority of research in this field, we measure income inequality at the Local Authority District level using the Gini coefficient of income inequality. The Gini coefficient describes the distribution of income within a particular spatial unit. It ranges from a minimum of 0 to a maximum of 1, whereby 0 would indicate that income is equally shared among all residents of an area and 1 that all income is held by 1 person or household. The United Kingdom is unusual in that the nine Government Office Regions represent the lowest spatial scale for which official ONS Gini data are available. We therefore use unofficial LAD Gini estimates constructed by Rae and Nyanzu , 2019b8Though evidence suggests that residents are able to detect higher and lower levels of income inequality as measured by the Gini coefficient  in GBP. Reflecting the approach adopted by Newman et al.  and Solt3.4We use linear multilevel models (estimated using the maximum likelihood estimator) to account for the hierarchical structure of our data, whereby individuals are nested in Local Authority Districts. In the first step, we estimate models with all controls in order to establish whether and how much LAD‐level income inequality affects meritocratic beliefs, all else being equal. In a second step, we introduce a cross‐level interaction between net household income and the LAD Gini coefficient (or 80:20 ratio) to test the hypothesis that the effect of income inequality is conditional on household income and establish the nature and direction of this relationship. All interaction models include a random slope on net household income as advised by Heisig and Schaeffer , and all44.1Model I in Table Model II in Table This pattern can also be seen in Figure 4.2Repeating Steps 1 and 2 with the 80:20 ratio of local income inequality rather than the Gini coefficient paints a similar but non‐identical picture. Against the expectations of Hypothesis 1, Model III in Table Where findings using this alternative specification of income inequality differ is in relation to wealthy respondents. Figure 4.3We conduct a number of additional analyses in order to probe the robustness of our findings, the results of which are displayed in the Appendix. Findings are robust to several alternative specifications of household income Tables  and A4 aSince more unequal localities tend to be more prosperous localities  inequality” proposed by Mijs . This exThis finding also means we should only cautiously use explanations that see belief in meritocracy as a conscious and explicit type of knowledge. Attitudes toward social status, social value, and individual merit are not purely cognitive and conscious phenomenon. These attitudes are not merely the result of the diffusion of information and the knowledge about theories of inequality. They probably also involve a sociopsychological comparison and justification dynamic. Principles of equality and fairness are likely to be embedded in how people perceive the social structure, how they situate themselves within social structures, and what prospect of future improvement they perceive to be realistic. More generally, this finding raises questions for studies comparing belief in meritocracy over time and between countries. If these meritocratic beliefs cannot be explained by patterns of spatial and social distancing, then we need to develop convincing alternative explanations.Second, the fact that we largely replicate Solt et al.'s  findingsgreater inequality provides richer individuals with the motive and the means to disseminate religion more widely throughout their societies  and a concept that can offer insight into the validity of the future advancement hypothesis: income satisfaction. Intuitively, one would expect income satisfaction among low‐income respondents to decline with rising income inequality and exposure to the more affluent; if it does not, then we take this as evidence for the future advancement hypothesis. To enhance comparability with our measure of meritocratic beliefs, we first rescale the original 7‐point Likert response scale to a 0–100 score, where 0 denotes completely dissatisfied and 100 completely satisfied. We then run additional linear multilevel models of income satisfaction, using exactly the same set of covariates employed in our analysis of meritocratic beliefs.In line with the future advancement hypothesis, findings  income, as well as stronger meritocratic beliefs suggests that these beliefs may well be turned toward the future. For the most economically vulnerable members of society, it is at least plausible that regular direct and indirect contact with others “who have made it,” coupled with the higher levels of economic dynamism in more unequal localities  information from multiple sources and life domains, including friends and family, news media, and even public entertainment Kim, . Our und6In this article, we contribute to a recent debate by undertaking the first assessment of the relationship between local income inequality and meritocratic beliefs outside the United States, using data from the UK Household Longitudinal Study. We find that the positive relationship between country‐level income inequality and meritocratic beliefs identified by Mijs  does notIn combination, our results have far‐reaching implications for a collective understanding of how income inequality affects individual well‐being and whether such inequality is self‐correcting. If higher levels of local income inequality did depress belief in the core premise of the western democratic system—either among the population as a whole or among the most economically vulnerable—then two things would follow. While there would be reasons to worry about the psychological effects of high levels of local income inequality, we could also expect greater bottom‐up demand for redistribution to emerge from unequal localities and self‐correction processes to kick in. But since we find no general association, and since living in places of higher income inequality is actually associated with higher levels of meritocratic belief (and income satisfaction) among those who are most economically vulnerable within England, the converse holds. There is less reason to worry about the unequal psychological effects of income inequality but there is also little prospect of system correction. Low‐income respondents are unlikely to embark on political action intended to overthrow the unequal status quo if they endorse meritocratic ideology with the same fervor as their much wealthier counterparts.In order to corroborate—or refute—this interpretation of the spatial and social distribution of belief in meritocracy, future research should dig deeper into how belief in meritocracy is linked to other attitudes, dispositions, and values. For instance, do low‐income individuals and families in highly unequal areas have a distinctive orientation toward the future? Is their belief integrated into a typical configuration of dispositions or attitudes? But as highlighted above, researchers must also dig deeper into the meaning of living in an unequal context: what does it mean to individuals, and what are the features of these unequal contexts in terms of neighborhood networks, local public spheres, and social interaction more generally?We thank the UK Data Service for their assistance in obtaining the special licence required to access restricted versions of Understanding Society used in this paper, and participants of the UNIL Parcours de vie et inégalités sociales seminar and the ECSR Annual Conference 2021 for their helpful comments and ideas. We would also like to express our thanks to the BJS editorial team and two anonymous reviewers for the pertinent and helpful feedback and the constructive spirit of challenge and engagement, which were both greatly appreciated. Open access funding provided by Universite de Lausanne.https://osf.io/svwn2/.Replication Stata syntax, which includes links to the individual and LAD‐level data employed in the analysis have been archived at:


To analyze student performance when using a sustainable teaching tool developed to guide learning toward interprofessional perspectives.This study compiled data about D4 students’ performance when using an interprofessional education (IPE) teaching tool reported previously in this journal, during their 5‐week Geriatric and Special Needs Program rotation in the academic years 2018–2019 and 2019–2020. Ninety‐two students were introduced to IPE concepts and teaching tools during their orientation. Students were then asked a question regarding the perspective of each healthcare team member and whether they would contact these healthcare team members for collaboration during the provision of oral care with regard to various patient cases. Students were scored on whether they answered the question about the perspective of each health care team member. The same two independent evaluators also noted whether the student thought each member of the health care team should be contacted.n = 70; 76.1%), followed by family caregivers , and pharmacists . The results of the interrater agreement between the two‐faculty scoring students were between 86.7% and 100%.A majority (90.2%–95.7%) of dental students applied their knowledge to questions regarding each health care team member's perspectives. The profession that dental students most often indicated they wished to contact for collaboration was primary care providers (The teaching tool is sustainable and succinct. Students considered the perspectives of each health care team member at a rate above 90%, and the interrater agreement was high among the faculty evaluators. Students considered contacting primary care providers, family caregivers, and pharmacists more often than the other health care team members. We see this model as one approach to begin the articulation of learning outcomes for IPP. A secondary purpose is to explore the students’ propensity for engaging fellow team members with their patients.3GSNP) rotation in the academic years 2018–2019 and 2019–2020 . This study compiled data about D4 students’ performance using an interprofessional education (IPE) teaching tool, during their 5‐week Geriatric and Special Needs Program , missed the step (M), or marked it as not applicable (N/A) to their patient/case. The same two evaluators also noted whether the student thought each member of the health care team should be contacted. The questions on who to consult elicited intuitive responses. The next step is to add structure to the discussion on who to consult and why. The same is true for the student intuitively designating a question as “Not Applicable.”These data reflect evaluations completed in three time periods between May 2018 and March 2020, and responses are split into three groups by time. Group 1 spans May 16, 2018, to December 12, 2018, group 2 spans February 6, 2019, to August 1, 2019, and group 3 spans September 11, 2019, to March 11, 2020.κ and percent agreement, calculated within each health care team member's question and combining responses from all three time periods. Because the interrater agreement was high across all categories, the first rater's answer for each question was used when possible, while the other rater's answer was only used if the first rater's answer was missing. These final data were tabulated overall and by time period. To examine differences in rates of different answers across the three groups, χ2 and Fisher's exact tests were used. All analyses were performed in R version 4.0.0 using a 5% significance level. We did not adjust for multiple comparisons.Interrater agreement between the two raters was assessed via Cohen's For primary care: Physical assessment as part of the Oral Surgery rotation and health histories of every patientPharmacology and Pharmacy courses and ongoing clinical consultsNutrition fundamentalsSocial work skillset in the 5‐week Geriatrics rotation and social work concepts in Quality Assurance assessments with patients.The didactic/clinical thread before implementation of the IPP skillset included:There were no explicit didactic courses in nursing or physical therapy.4n = 88 to n = 83 depending on the question) asked and responded to the question for each discipline. A lower percentage of students recommended contacting any of the disciplines than asked and responded to the provider question from each discipline. Results are in Table n = 83), “Social Work” (n = 83), and “occupational therapy/phylical therapy” (n = 83). The discipline that dental students most often indicated they wished to contact for collaboration was primary care providers , followed by family caregivers , and pharmacists . Less commonly indicated to be contacted were nurses , nutritionists , and physical therapists/occupational therapists . The results of the interrater agreement between the two‐faculty scoring students were between 86.7% and 100%. Students who were judged to “Apply” a step were almost always judged to “Grasp” the meaning of the step. Although there are no data to show student performance in systematically asking the questions of each discipline before the IPP exercise was introduced, faculty agree that students did not explicitly ask discipline‐based questions before the learning exercise was introduced. The question, “Do you recommend contacting a team member about this patient?” was also significantly different in the family caregiver—groups 2 and 3 had higher rates of contacting the family caregiver than group 1 (p < .001). No other significant differences were seen.A high percentage of students asked and responded to the provider question for each discipline. Results are in Table 5This Emulation Model for IPP is shown as sustainable in eliciting dental students to systematically ask and respond to questions deemed important for every member of the health care team to ask regarding the next patient. The collective thought processes of the team members became the learning outcome, learning guide, and assessment instrument. The high‐performance rate  is interpreted to mean that the exercise was effective in engaging students in incorporating the initial thinking of each discipline. The lower percentages of students who would recommend contacting respective disciplines is more difficult to interpret. One explanation could be that the student had enough confidence to manage the patient without actual consultation. A future direction in refining the exercise will be to add the question, “Why would you contact team member X?” Some association is seen between exposure to explicit clinical or clinically oriented material (whether didactic or in‐clinic) and articulation of that discipline in the IPP exercise. The inclusion of “primary care provider” was most articulated by students and is the area with more extensive didactic and clinical exposure. Pharmacy is next most common in the IPP exercise and also has extensive didactic and clinical exposure. Nursing is less frequently cited and is associated with no explicit didactic content in Nursing. Similarly, there is no explicit instruction in Physical Therapy in the dental curriculum. Nutrition has an extensive didactic component, but not a clinical rubric. Social work has little explicit didactic coursework, but there is an extensive quality assurance component with elements of social work. Yet to be determined is how effectively the students will be in identifying explicit patent problems once the question is asked. Also, yet to be determined is the effectiveness of the student in recommending treatments for the patient once the question is asked and responses are obtained.Having established sustainability and practical application for the emulation model for IPP, the next step is to articulate how effective students could be in improving patient acceptance of recommended treatment using this model. It is likely that a separate critical thinking skill will be needed to guide learning on patient adherence to recommended treatment.While beyond the scope of this project, the next step would be to find the impact on patient outcomes (Glick et al., 6Generalizations of the conclusions to other health disciplines have limitations, yet the conclusions are mostly common sense regarding other disciplines and would seem to have some generalizability.7After 2 years, the critical thinking model for IPP is seen to be sustainable and succinct. In this 2‐year observation period, students considered the perspectives of each health care team member at a rate above 90%, and the interrater agreement was high among the faculty evaluators. While we do not expect for students to have an in‐depth grasp for the thinking of an experienced health team member from another discipline, results are seen as a first step in at least considering the first priority question for each team member. We are not aware this step has been previously taken. For student patient/cases in the Geriatrics and Special Needs Clinic, students considered contacting primary care providers, family caregivers, and pharmacists more often than the other health care team members. Since the initial reporting of implementing this model, we are not aware of other models emerging with explicit learning outcomes for IPP.Trevor W. Craig: Participation in designing the project, collating raw data, reviewing data, and designing and reviewing the manuscript. Carissa L. Comnick: Participation in designing the project, reviewing data, conducting statistical tests, designing tables, and designing and reviewing the manuscript. Kecia S. Leary: Participation in designing the project, in reviewing data, and designing and reviewing the manuscript. Jennifer E. Hartshorn: Participation in designing the project, conducting seminars where data were gathered, reviewing data, and designing and reviewing the manuscript. David C. Johnsen: Participation in designing the project, reviewing data, and designing and reviewing the manuscript. Leonardo Marchini: Participation in designing the project, conducting seminars where data were collected, reviewing data, and designing and reviewing the manuscript.The authors declare no conflict of interest.


Lung transplantation (LTx) is a lifesaving procedure burdened with limited long‐term survival. The most common cause of death after LTx is chronic lung allograft dysfunction (CLAD). Today, useful biomarkers for the detection of CLAD are lacking. Circulating cell‐free DNA (cfDNA) is released during cellular decay and can be detected using polymerase chain reaction (PCR). Thus, donor‐derived cfDNA in recipient serum indicates cellular decay in the transplanted organ. In the current study, we explore the possibility of using a novel PCR method to detect cfDNA as a biomarker for clinical events, especially CLAD.Four patients were retrospectively tested for levels of both donor and recipient‐derived cfDNA using digital droplet PCR after targeted preamplification. The results were correlated to recorded clinical events.p = .0015).All available samples rendered results. Both patients that later developed CLAD showed a persistently elevated ratio between donor‐and recipient‐derived cfDNA. Also, the mean level of cfDNA was higher in the two patients who later developed CLAD than in patients who did not  covaries with chronic lung allograft dysfunction (CLAD) and infectious severe events in a proof‐of‐concept study of a novel method for biomonitoring of lung transplant recipients. Almost 70,000 lung transplants have been performed internationally until today,Cell‐free DNA (cfDNA) is released from cells into the surrounding tissue and bloodstream during apoptotic and necrotic cellular decay and can be detected in plasma and serum.To evaluate the potential usefulness of the method for lung transplant recipients, this pilot study aimed to in a limited, select population, explore the potential association between levels of PCR‐detected cfDNA in serum and the timing and severity of various clinical events, with a particular emphasis on CLAD after lung transplantation.22.1g and aliquoted before they were frozen at −80°C within 24 h after sampling. Surveillance of infectious complications was performed with a multiplex real‐time PCR assay as previously describedNinety‐eight patients who underwent LTx between 2009 and 2011 at Sahlgrenska University Hospital were prospectively included in a follow‐up study designed to investigate the impact of infectious complications on the outcome following LTx. Data from this study has been the subject of previous publications.Four patients were selected for this exploratory proof‐of‐concept investigation. Eligible patients were patients without retransplantation, with not more than three recorded clinical events and at least five sequential serum samples available. Patients with variable FEV1 and CLAD at end of follow‐up were identified from this group. Patients without CLAD and intermittent FEV1 loss during follow‐up were identified as controls. From each of these two groups, two patients were selected at random. For the current study, both CLAD diagnoses were reevaluated to be adherent to the 2019 definition.The laboratory staff was blinded to all clinical and patient‐related data. Serum samples were identified by serial numbers only during analysis and data management.Base immunosuppression protocol for each patient is outlined in Table CLAD was defined as an irreversible loss of >20% of baseline FEV1, confirmed with at least two spirometries at least 3 weeks apart, where other differential diagnoses had been excluded. Furthermore, treatment with azithromycin for at least 3 months without any signs of restitution was added as a criterion to be included as definitive CLAD in the current study.2.2Whole blood samples were used for genotyping. Donor and recipient genomic DNA was extracted from EDTA‐blood preparations using the DNeasy Blood & Tissue Kit (Qiagen).Serum samples were used for longitudinal detection of cfDNA. cfDNA was extracted from 0.25 to 1.25 ml serum using the QIAamp® Circulating Nucleic Acid Kit (Qiagen) according to the manufacturer's protocol. Concentrations of cfDNA were quantified with the Qubit® 3.0 Fluorometer (Thermo Fisher Scientific), fragment sizes were analyzed with the 4200 TapeStation (Agilent Technologies). A panel of 35 highly polymorphic SNP (single‐nucleotide polymorphism)‐assays2.3Target preamplification of cfDNA was performed using pooled primers from the 35 SNP panels. The preamplified cfDNA was quantified by ddPCR using specific single SNP assays from the SNP panel, based on the difference in genotypes between the recipient and its donor. Multiple SNP assays were used for each patient, all experiments included no template controls. The copies generated by droplet ddPCR for each allele at each SNP locus were calculated using Quanta Soft (Bio‐Rad). The mean value from triplicate assays was used to calculate the absolute levels of dd‐cfDNA, rd‐cfDNA, and DF. DF was defined as the percentage of dd‐cfDNA of the total amount of cfDNA.The dd‐cfDNA, rd‐cfDNA, and DF levels were compared with clinical events focusing on the relationship between elevated DF and CLAD.2.4The efficiency of target‐specific preamplification was determined using a cfDNA control, from normal donor plasma, in the range of 0.5–32 ng. cfDNA was preamplified in a single multiplex reaction for 10 cycles and monitored for individual SNP assays by real‐time PCR and SYBR‐green in triplicates. The quantitative real‐time PCR (qPCR) profiles for the SNP assays used in this study are shown in Figure Limit of blank (LOB), limit of detection (LOD), and limit of quantification (LOQ) were defined based on guidelines in Reference . ReferenThe LOB was set as the highest level of donor DNA that might be found when replicates of blank samples (no donor genome present) are tested: LOB = mean (blank) + 1.645 × SD (blank). The LOD was set at the lowest copy number concentration that could be distinguished from LOB with >95% certainty: LOD = LOB + 1.645 × SD (low‐concentration sample). The LOQ was set as the lowest analyte concentration for which the method provides results with an acceptable uncertainty.2.5U test. p < .05 was considered statistically significant.All graphs were made using GraphPad® Prism 9.0.2. Values were shown as median with standard deviation. Comparisons at the group level were performed using the Mann–Whitney 33.1The efficiency of preamplification was determined using a cfDNA standard and qPCR to monitor individual SNP assays. The qPCR profiles for the SNP assays are seen in Figure R2 values determined for each dilution series of the respective assay were >0.99 in all cases indicating that the assays were sufficiently accurate to allow LOQ = LOD  among patients who developed CLAD within the follow‐up period (Figure The mean levels of dd‐cfDNA of all samples collected within the entire follow‐up period of the first 36 months were higher (4We propose a novel method for detecting and quantifying both dd‐cfDNA and rd‐cfDNA that can be performed using frozen serum samples at a low cost and a rapid analysis turnover. The levels of the different origins of cfDNA are associated with clinical events where the elevation of dd‐cfDNA mirrors damage to the graft. Raised levels of rd‐cfDNA correlated with several infection episodes of the host. We recorded a doubling of the levels from an individual baseline associated with a recorded clinical event in close proximity in all but two cases. A consistently elevated DF was preceding CLAD diagnosis in both patients and noted up to 6 months before CLAD was evident.The events with observational proximity in time, between event and cfDNA elevation, are all of a more severe nature. The three events where both rd‐cfDNA and dd‐cfDNA were elevated represent infectious complications. Most interestingly, one of those is a symptomatic common cold coronavirus respiratory tract infection, previously suggested to be associated with long‐term CLAD development.There were two recorded clinical events without any marked elevation of cfDNA from either donor or recipient. These cases were an asymptomatic rhinovirus infection and a case of VZV reactivation with shingles, indicating that these two events represent less severe complications. Quantification of cfDNA could thus possibly be used to determine the clinical importance of infectious events in conjunction with other tests. This could possibly differ severe infectious events from those of limited importance at an earlier stage.In‐detail interpretation of the results from each of the patients is warranted. For Patient 1 Figure  showed eThe average amounts of dd‐cfDNA were higher in the two patients that eventually developed CLAD during the sample period Figure . This isde Vlaminck et al.Notably, in Agbor‐Enoch et al.'s study,All of the samples were stored frozen for more than 5 years in the present study. The study was designed to detect a vast majority of infectious events and combined surveillance testing with testing in acute events. Thus, the samples are very well suited to investigate the viability of the current method as a biomarker. The high temporal accordance between cfDNA and clinical events implies that the method might be possible to use in a clinical setting. It also shows the advantage of having dd‐cfDNA and rd‐cfDNA levels measured as well when interpreting DF. The results also confirm the capacity to analyze previously frozen sera. The possibility of freezing and storing samples opens up for sampling at a secondary site which means that the rather complicated method only needs to be set up in a limited number of laboratories to cover one or several transplant programs.The study analyzed a limited number of patients. This and the retrospective design leads to limited direct clinical usefulness of the results. The samples were not collected and prepared according to the currently used protocol.Future studies of the current method for cfDNA analysis in lung transplant patients need to be in larger cohorts to define inter‐patient variability better. The studies should include analyses of cfDNA response to different non‐CLAD types of allograft injury, such as infections, acute rejection, and biopsies, as demonstrated in the current study. Also, cfDNA response to different types of CLAD as well as post‐CLAD dynamics of cfDNA needs to be analyzed. Furthermore, prospective sampling in parallel with current monitoring practices, for example, donor‐derived antibodies, would be of great interest.In conclusion, the present pilot study shows that analysis of the quantity and relative proportion of donor‐ and recipient‐derived cfDNA using this novel method is feasible and that circulating levels may reflect important clinical events like allograft damage and significant infectious complications following lung transplantation. The results hint at the possibility of the method being used to detect CLAD. Further prospective research is warranted to validate the measurement of cfDNA to predict complications in a clinical setting.Jesper M. Magnusson conceptualized the idea, compiled data, interpreted data, drafted the manuscript. Anne Ricksten was pivotal to the methodology, supervised the laboratory analyses, supervised data accuracy, interpreted data, and contributed to the writing of the manuscript. Göran Dellgren supervised the study and contributed to the writing of the manuscript. Carina Wasslavik performed the laboratory analyses and contributed to the writing of the manuscript. Rickard Nordén refined the idea, interpreted data, and contributed to the writing of the manuscript. Johan Westin refined the idea, managed overall performance of the study, interpreted data, and contributed to writing the manuscript. Jens Boehmer conceptualized the idea, Interpreted the data, and contributed to writing the manuscript.Supplementary information.Click here for additional data file.Supplementary information.Click here for additional data file.


Calidris alpina schinzii. As predicted by the APH, survival from nest predation was positively linked to spring small mammal abundance and negatively linked to autumn small mammal abundance. Importantly, local recruitment showed opposite responses. This counterintuitive result may be explained by density‐dependent survival. When nest depredation rates are low, predators may show stronger numerical and functional responses to high shorebird chick abundance on coastal meadows, whereas in years of high nest depredation, few hatching chicks lure fewer predators. The opposite effects on nest and local recruitment demonstrate the diverse mechanisms by which population size variation in primary prey can affect dynamics of alternative prey populations.Generalist predators using small mammals as their primary prey are suggested to shift hunting alternative prey such as bird nests, when small mammals are in short supply . Nest survival and survival of young individuals should be positively linked to small mammal abundance and negatively linked to predator abundance, but little information exists from survival of chicks, especially until recruitment. We test these predictions of the APH using 13 years (2002–2014) of life history data from a ground nesting shorebird breeding on coastal meadows. We use small mammal abundance in the previous autumn as a proxy for spring predator abundance, mainly of mammalian predators. We examine whether small mammal abundance in the spring and previous autumn explain annual variation in nest survival from depredation and local recruitment of the southern dunlin  Using long‐term life history data, we show that nest survival and juvenile survival of a precocial shorebird are linked to the regional small mammal abundances during the breeding season and during the previous autumn. While these results support the alternative prey hypothesis, they also show that variation in small mammal abundance can have different impacts on different life history stages of the alternative prey. As in many ground‐nesting bird populations, the most common cause of nest failure is nest depredation . We have collected individual based data from this population since 2002  were recorded. These species fluctuate synchronously , which is situated roughly 10 km east from the city of Oulu. The trapping area is ca. 30–50 km from the study meadows, but vole abundances can be safely assumed to reflect abundances in study area because of much larger scale geographical synchrony in their population dynamics . We started with a general model [Φ(age1t/age2c) p(age1t/age2c)]. This model included the effect age (age: juveniles age1 vs. adults age2). Survival and recapture probabilities were constant in time for adults (age2c) but time‐dependent for juveniles . This model fit the data . We were not able to reliably estimate survival in 2004 because only 9 chicks hatched. Hence, we separated the year 2004 with a separate parameter and fitted the covariates to years (2002–2003 and 2005–2014).We used program MARK to analyze local recruitment  using an age‐dependent version of the CJS model . If the autumn small mammal abundance affects how well the predators and their offspring survive from autumn to the next breeding season, it should be linked to the amount of predators in the next breeding season, and we can expect that there is a negative association between previous autumn small mammal abundance and survival. Local recruitment includes both pre‐fledging survival (period before chicks are capable of flying) and post‐fledging survival (period after starting to fly) until age of one year. In shorebirds such as the dunlins, local recruitment reflects mostly pre‐fledging survival rather than survival during the post‐fledging period  models to examine temporal variation in survival and to allow estimation of the percentage of temporal variation explained by covariates (see below). We compared the time‐dependent model with a constant (intercept only) model to check for annual variation in survival. After this, we fitted models where survival was a function of linear or quadratic effects of (1) spring small mammal abundance and/or (2) previous autumn small mammal abundance. Here, spring abundance is the number of small mammals trapped per 100 nights during the same spring as the nests were followed and juveniles hatched (year t). If the generalist predators switch to hunting shorebird eggs and chicks when the small mammal abundance is low, we can expect a positive association between small mammal abundances and survival. Previous autumn small mammal abundance is the number of small mammals trapped per 100 nights during the autumn of the previous year  is the deviance from the constant model, Dev(cov) is deviance from the covariate model and Dev(t) is the deviance from the time‐dependent model  to calculate the percentage of annual temporal variation explained by the covariate(s) as follows:We used the Akaike's information criterion corrected for small sample size AICc when comparing support for nest survival models and the Quasi‐AICc when comparing support for models explaining local recruitment  survive, these species provide shelter for smaller shorebird species by deterring avian predators such as corvids and birds of prey  and the alternative prey occupy the same areas, and predators switch to depredating bird nests when small mammal are low in abundance  can create further variation.Our best models explained 55% of annual variation in nest survival. The unexplained part of temporal variation in the depredation of nests can be linked to multiple processes. For example, annual variation in the number of breeding larger wader species that deter avian predators from the breeding sites  may cause annual variation in nest depredation of smaller species such as the dunlin. Furthermore, predators that specialize in small mammals can show varying behavior, and their population sizes can be affected by conditions during the annual cycle such as spread of diseases, competition or predation that that may not linked to small mammal abundance. Finally, depredation by predator species that do not specialize in small mammals when they are abundant  chicks in years with high vole abundance. Such a pattern could be explained by the apparent competition hypothesis, i.e., incidental depredation of chicks by predators that were after small mammals . The nature of the breeding sites, i.e., distinct patches that are surrounded to a large degree by forest and reedbeds, may facilitate this pattern, especially when broods of most shorebird species aggregate to the shoreline.Intriguingly, we found that small mammal abundance in the spring and autumn caused opposite effects on local recruitment compared with nest depredation. Survival of chicks from hatching until age one was lower when spring small mammal abundance was high and small mammal abundance in the previous autumn was low. Our result is similar to Ludwig et al. , who repWe show that variation in nest success of a ground nesting shorebird is linked to the abundance of small mammals. This link may be formed by generalist predators switching to alternative prey, such as shorebird nests, when small mammals are low in abundance. If this is the case, the observed pattern has important conservation implications as many ground nesting bird species, including a number of shorebirds, suffer from increased nest depredation and are declining in numbers ; data curation ; formal analysis (lead); funding acquisition ; investigation ; methodology (lead); project administration ; resources ; supervision ; writing – original draft (lead); writing – review and editing . Risto Tornberg: Conceptualization ; data curation ; formal analysis ; investigation ; methodology ; project administration ; resources ; supervision ; writing – review and editing . Eveliina Airaksinen: Conceptualization ; formal analysis ; methodology ; resources ; writing – review and editing . Nelli Rönkä: Data curation ; methodology ; resources ; writing – review and editing . Kari Koivula: Conceptualization ; data curation ; formal analysis ; funding acquisition ; investigation ; methodology ; project administration ; resources ; supervision ; writing – review and editing .The authors declare that they have no conflict of interest.


Most wireless localization methods utilize only one means of detection for the surgeon, sufficient to localize a single small breast lesion for excision. Complex cases requiring bracketing of a larger lesion or localization of two or more close lesions can superimpose the signal from separate “seeds” with such methods. The lack of discernment between the localization “seeds” can disorient the surgeon, risking a missed lesion on excision and longer operative times. with the use of neoadjuvant chemotherapy prior to breast surgery, the necessity of localizing both a breast lesion and an axillary lymph node previously biopsied is becoming frequent.A 44 year‐old woman underwent neoadjuvant chmotherapy for a breast cancer the did not express estrogen receptor, progesterone receptor, or HER2 receptor. In establishing the extent of disease, a suspicious ipsilateral lymph node was biopsied and found to contain metastatic disease. She had an excellent response to the chemotherapy, with decreased size of the primary tumor and the previously biopsied lymph node. The patient desired breast conservation. The primary tumor and associated calcifications were bracketed using two different Smartclips™, with a third localizing the lymph node biopsied.This report illustrates how the use of three SmartClips™, within the EnVisioTM system, allowed for separate tracking of each “seed” throughout a complex surgery in a patient following neoadjuvant chemotherapy. This resulted in successful resection of both the tumor and the tagged lymph node. This presents a dilemma to the consulting surgeon. Prior to screening, excisional breast biopsies were based on palpation. Without haptic guidance, the placement of a needle and wire with imaging guidance on the morning of surgery became the method of choice for preoperative localization as it was widely available and relatively inexpensive. In the case of more extensive disease, multiple wires were frequently placed in the breast to localize larger or multiple areas, and wires were rarely placed in the axilla for localization of lymph nodes.Wire localization has its limitations and challenges, including migration or displacement of the wire prior to a patient's arrival in the operating suiteIntraoperatively, the success of wire localization depends on the surgeon's mental reconstruction of the images, the trajectory of the wire, and the perceived intraoperative position of the lesion.Wireless “seed” localization techniques have been developed to allow for greater flexibility in beginning an early operative day incorporating localization. This uncouples the tight time reliance of the surgeon on the radiologist's performance of the wire localization prior to the surgical resection. These newer “seed” methods include but are not limited to the use of a radioactive iodine‐125 seed, a radiofrequency identification tag, the SAVI® Scout  implantable non‐radioactive infrared‐activated electromagnetic wave reflector, or one that utilizes magnetic detection . Multiple series have described the utility of these approaches in excising non‐palpable breast lesions.With the increased utilization of neoadjuvant chemotherapy for breast cancers, newer algorithms for application of axillary sentinel lymph node biopsy are evolving in the management of the patient who presents with cN1 disease that converts to cN0 following chemotherapy.2The University of Cincinnati database on breast disease, approved by the Institutional Review Board, includes data relative to breast cancer and its treatment (IRB 2019 ‐0147). Separate consent was obtained from this single patient for case report purposes. UC Health switched to use of the SmartClip™ in localizations of the breast and axilla in 2019. The application of this localization technique can include biopsy‐proven breast cancers, benign lesions, as well as lymph nodes.This patient is a 44‐year‐old woman, originally from the Ivory Coast, who had was found to have a benign cyst in the left breast on her first screening mammogram the year previous. Her screening mammogram in July 2020 revealed new calcifications. Anterior to these calcifications was the previously described cyst, unchanged. Diagnostic mammogram of the left breast at that time showed a 1.4 cm grouping of pleomorphic calcifications in the upper outer quadrant. Ultrasound of the left breast was performed for further evaluation due to the patient's breast density, which also demonstrated an irregular 3.6 cm mass associated with the calcifications. Ultrasound of the left axilla demonstrated a suspicious left axillary lymph node. The suspicious left breast mass and lymph node underwent ultrasound‐guided core needle biopsy. Screening and diagnostic workup was performed at the Breast Imaging Center within the Barrett cancer Center at the University of Cincinnati Medical Center, in Cincinnati, Ohio, USA. Pathology revealed primary invasive ductal carcinoma associated with high‐grade ductal carcinoma in situ in the breast, as well as carcinoma metastatic to the biopsied lymph node. Tissue markers were left in both the diagnosed cancer as well as the affected lymph node at the time of biopsy.The pathology of the left breast primary cancer revealed invasive ductal carcinoma, high grade. The receptor profile of this patient's tumor proved negative for estrogen receptor, progesterone receptor and HER2/neu receptor expression, with 50% proliferation inferred by Ki‐67 immunohistochemical staining. She was referred for consultation with a surgical oncologist as well as a medical oncologist. She stated that she had no symptoms relative to feeling a new mass, any focal pain, or nipple discharge. She had no reported weight loss and enjoyed a high quality of life. She had no symptoms to suggest distant metastatic disease, and her CT scans of chest, abdomen and pelvis failed to demonstrate any metastasis. On physical exam, the mass measured at least 4.0 cm, including overlying skin, with use of external calipers. An enlarged, mobile left axillary node was appreciated also. Given the size of the tumor and the triple negative receptor profile, the standard of care strongly supported initiation of neoadjuvant chemotherapy prior to surgery.The patient underwent a medical port insertion for ease in venous access for treatment. She received four doses of doxorubicin and cyclophosphamide, cycling every 2 weeks, followed by eight weekly doses of paclitaxel. She returned for evaluation prior to surgical resection as she completed her regimen. She demonstrated a remarkable clinical improvement, with no palpable mass or palpable ipsilateral lymph node at the completion of chemotherapy. Repeat imaging confirmed marked decrease in size of the breast mass and the known affected lymph node, with no appreciable change in the extent of the suspicious calcifications. Since she desired breast conservation, we proceeded to prepare for a left partial mastectomy in addition to left axillary sentinel lymph node biopsy. In addition, a targeted axillary dissection of the previously biopsied lymph node (tagged) would be included, as it had proven to be positive for metastatic breast cancer cells prior to neoadjuvant therapy. A completion axillary lymph node dissection would follow if she should have any tumor cells within the lymph nodes excised.Inclusion of the previously tagged positive lymph node in the resection, if proven to be a sentinel lymph node as well, would lower the false negative rate in the context of the sentinel lymph node biopsy.2.1The SmartClip™ is a fiducial composed of a non‐radioactive ferrite core with parylene C coating, measuring 8 mm in length and 1.4 mm in diameter  was placed in a syringe with 15 ml sterile injectable saline solution. After she was cleansed and draped, the syringe of methylene blue dye with saline was injected subcutaneously under her left areola at four equidistant points. This was then massaged for 10 min.Figure The EnVisio™ Navigator was placed on the electrocautery pen; through interaction with the “pad” under the patient, its use locates the position of the SmartClip™‐tagged axillary lymph node, or either of the two SmartClips™ bracketing the cancer, depending on which SmartClip™ is chosen for primary detection. The “Heads Up Display” (HUD) screen was mounted pre‐operatively on the drape pole to the patient's right, across from the operating surgeons. Detection of the SmartClips™ was confirmed on the EnVision View Figure  of the HThe sentinel lymph node biopsy and targeted axillary dissection were performed first. An incision was planned under the left axillary hairline for a length of approximately 3 cm. After the incision was made and extended through the dermis, the location of the SmartClip™ tagged node was easily checked for depth and relative location on a regular basis since the electrocautery and Navigator are attached Figure . The HUDen bloc. An intraoperative specimen radiograph was obtained separately for the breast specimen and the images were forwarded to the breast radiologist for confirmation.A radial incision was planned for the left partial mastectomy in the lateral left breast at approximately the 2:30 position. Initially, the HUD demonstrated that the Pink and Green SmartClips™ were close from an anterior perspective as they appeared superimposed in position over the detection cassette under the pad beneath the patient's back Figure . However3The pre‐operative localization of the previously biopsied left axillary lymph node with a SmartClip™, as well as the use of two Smartclips™ to bracket the extent of left breast cancer using techniques similar to other seed methods, proceeded without difficulty. A final post‐procedure mammogram confirmed adequate position of all three SmartClips™ relative to their targets Figure .). Intraoperative frozen section of this first node demonstrated residual metastatic disease, which was sufficient to prompt the completion left axillary dissection.The first left axillary sentinel lymph proved to be the lymph node that initially contained metastatic disease prior to neoadjuvant chemotherapy. This was confirmed by intraoperative specimen radiograph of the lymph node, which also revealed the tissue marker and the SmartClip™ Figure . IntraoThe bracketed SmartClip™‐localized partial mastectomy specimen revealed residual invasive ductal carcinoma on specimen radiograph, present as scattered tumor cell clusters measuring up to 5 mm within a tumor bed of 1.2 cm, consistent with treatment‐related change Figure . Surgica4Use of the EnVisio™ system, with precise distances of the operating electrocautery unit to the localized SmartClips™ enabled a complex case to be approached with greater confidence. This was reinforced by the ability of the surgeon to continually monitor the distance of the operating electrocautery unit relative to the Smartclip™ of concern. Intraoperative radiographs of specimens removed that were localized would be performed in the context of any localization method, but that feedback is only upon completion of the dissection.Traditionally, this case would have been performed as a multisite needle localization the morning of the surgery. The coupling of radiology and surgery schedules has led to significant stress for both disciplines in the recent past, given the increased push for time efficiency to reduce escalating costs. As in the case of a complicated needle localization, the radiologist may feel pressure to perform the procedure quickly to accommodate the surgical schedule. Multiple imaging modalities would have been necessary in this case to bracket the malignant calcifications under mammographic guidance and to localize the lymph node under ultrasound guidance. The complexity of placing three wires can require extra time in planning the procedure on the morning of surgery.A primary advantage of wire‐free localization methods is uncoupling of the radiology and surgery schedules. Radioactive iodine‐125 seed localization (RSL), and SAVI Scout® radar (SSR) inserts demonstrate significantly less patient delay preoperatively as compared to wire localization.SAVI Scout® radar inserts in a similar fashion to the other seed type methods and the wire localization method.In addition, radiofrequency identification tags (RFID) , Magseed® , and SmartClip™ are all seed‐type wireless localizers placed independently of the day of surgery, resulting in fewer delays on the day of surgery. Patient comfort is improved on the day of localization without the added stress of surgery and NPO status. The patient is also more comfortable the day of surgery since there are no external components for the patient to manage as with wire localizations. Placement of a wire in the axilla can be particularly uncomfortable for patients and subject to migration in the duration between placement and excision due to fidgeting. These seed type wireless localizers all avoid the risk of complications associated with an external wire component and do not impact the surgical approach to excision or the location of the incision.Studies published that examine resection margin status in using wire‐guided localizations, RSL and SSR, Magseed® and RFID appear to be comparable or slightly improved over wire localization in obtaining negative margins on excision.This article describes localization and successful excision with more than one SmartClip™ seed. With some implanted localization devices, differentiating between the seed locations could become a challenge. This article describes the use of three separate SmartClips™ placed and excised without difficulty; one of these clips was used to tag a lymph node previously marked and known to be positive for metastatic disease prior to neoadjuvant chemotherapy. Certainly, multiple localizations have been described using wire localizations,In the shift toward increasing use of neoadjuvant therapy prior to definitive surgical management of breast cancer, wireless localizations are playing an increasingly important role in the localization of biopsy‐proven metastatic axillary lymph nodes in patients with breast cancer following systemic therapy. In light of our experience, up to three SmartClips™ could be inserted at the time of biopsy, or closer to surgical date. To our knowledge, this is the first report of use of the SmartClip™ for localization, and only one of a handful of reports utilizing three sites of localization. Yet, three localizations are no longer rare in this context and use of the SmartClip™ and its clear differentiation from other sites made the case straightforward.SmartClips™ are approved by the FDA for both temporary and permanent insertion within the breast tissue.5The use of the SmartClip™ fiducial proved successful in its application to the setting of multiple localizations for surgical excision. The continuous feedback to the surgeon as to resection location relative to the Smartclip™ position easily enabled a timely excision of multiple sites.Elizabeth A. Shaughnessy: Conceptualization ; data curation ; formal analysis ; investigation ; methodology ; visualization ; writing – original draft ; writing – review and editing . Charmi Vijapura: Investigation ; methodology ; writing – original draft ; writing – review and editing . Chantal Reyna: Conceptualization ; formal analysis ; investigation ; methodology ; writing – original draft ; writing – review and editing . Jaime Lewis: Conceptualization ; methodology ; writing – original draft ; writing – review and editing . Kyle Lewis: Methodology ; writing – original draft ; writing – review and editing . Su‐Ju Lee: Methodology ; writing – original draft . Lawrence Sobel: Methodology ; writing – original draft ; writing – review and editing . Rifat Wahab: Methodology ; writing – original draft ; writing – review and editing . Lauren Rosen: Visualization ; writing – original draft ; writing – review and editing . Ann Brown: Conceptualization ; data curation ; formal analysis ; investigation ; methodology ; visualization ; writing – original draft ; writing – review and editing .Dr. Chantal Reyna recently became a consultant for Elucent Medical. The remaining authors have explicitly stated that there are no conflicts of interest in connection with this article.The study was approved by the Institutional Review Board of the University of Cincinnati (protocol #2020‐0675) and written informed consent was obtained.


Strigolactones are phytohormones with many attributed roles in development, and more recently in responses to environmental stress. We will review evidence of the latter in the frame of the classic distinction among the three main stress acclimation strategies , by taking osmotic stress in its several facets as a non‐exclusive case study. The picture we will sketch is that of a hormonal family playing important roles in each of the mechanisms tested so far, and influencing as well the build‐up of environmental memory through priming. Thus, strigolactones appear to be backstage operators rather than frontstage players, setting the tune of acclimation responses by fitting them to the plant individual history of stress experience. Strigolactones act as backstage operators rather than frontstage players in stress acclimation strategies , by tuning them to the plant individual history of stress experience. The second is tolerance, which is conspicuously acquired via the mitigation of stress impact by structural and biochemical mechanisms. The third is escape, which is mainly achieved by altering the pace of the developmental programme as to shorten the life cycle, and flower shortly after drought recovery. It must be emphasized that the boundaries between these schematic paths may be blurred, in that plants may adopt a combination of strategies depending on the species, but also on the intensity and the speed of stress onset , which affects the ability of the plant to acclimate to the incoming stress  and non‐canonical ones, in which the A, B or C rings are missing. A further distinction is between strigol‐ or orobanchol‐type strigolactones, depending on the orientation of the C ring  and the carotenoid cleavage dioxygenases (CCD) 7 (MAX3/D17/HTD1/RMS5/DAD3) and CCD8   leading to hydroxylated carlactone, which may in turn act as the precursor of as‐yet unidentified strigolactones , tomato (Solanum lycopersicum) and cowpea (Vigna unguiculata)  , an α/β‐fold hydrolase protein which retains enzymatic activity but with extremely low turnover. This implies that the hormone is rather slowly hydrolysed to a tricyclic ABC and a bri1‐EMS‐suppressor 1 (BES1), which was initially characterized as a positive regulator in the brassinosteroid signalling pathway and later proposed as a regulator of strigolactone‐dependent shoot branching  because its mutant, while not affected in strigolactone perception, is insensitive to compounds named karrikins. These are abiotic in origin, as they are smoke components produced by combustion of plant tissues; they act as germination stimulants for fire‐succession species and structurally share a butenolide ring with strigolactones  to describe the effects of exogenous strigolactones further obfuscated the picture, since it contains two stereoisomers, GR245DS and GR24ent‐5DS  is less potent than GR245DS but more specific to D14 stimulation in arabidopsis  in green algae, before the evolutionary appearance of obvious perception and signalling components, rather suggests an exogenous role for ancestral strigolactones. This hypothesis is strongly supported by the recent identification of the novel strigolactone molecule bryosymbiol in the bryophyte 4DO could stimulate degradation of SMXL2 specifically and unexpectedly downstream of D14   are unrelated to strigolactones. However, given the demonstrated upward mobility of strigolactone themselves in the xylem parenchyma, and their ability to repress their own biosynthetic pathway, it may also occur directly, with the loss of root‐derived strigolactones de‐repressing synthesis in the shoot under drought   and nitric oxide production in arabidopsis  Figure . Given t4.1Brassica napus L.)       , DMTU  or EGTA  can reverse the positive effect of rac‐GR24 treatment on salt‐stressed plants, as observed in cucumber  have been tested during salt stress in tomato. GSNO has similar effects as rac‐GR24 in terms of increased antioxidant enzyme activity and chlorophyll content, mitigating the damage caused by salt exposure. However, in the presence of TIS108 (a triazole‐type strigolactone synthesis inhibitor), the protective role of NO during salt stress is reduced, suggesting that strigolactones are necessary for the NO‐induced protective response to salt stress   in leaves of grapevine (Vitis vinifera L.) under PEG‐induced osmotic stress, by allowing to maintain net carbon assimilation rates in the presence of lower stomatal conductance. GR24 treatment is also associated to lower electrolyte leakage and increased water and chlorophyll content compared to the non‐treated, stressed plants, which may be seen as both a feature of increased stress tolerance, and of avoidance. In this experimental set‐up, though, the enzymatic and non‐enzymatic antioxidant system was less activated and yet, the H2O2 and MDA content were lower in GR24‐treated plants. This suggests that stress was rather avoided than better tolerated; however, the work lacks appropriate controls on GR24‐treated, unstressed plants  lines silenced for CCD8 do not flower at all (Pasare et al., CCD8 silencing causes fewer and smaller flowers and fruits (Kohlen et al., max2 plants have delayed flowering (Rasmussen et al., A missing part of the picture is whether strigolactones may also regulate stress escape by affecting the timing of flowering. While direct evidence is sorely needed, several clues suggest that they might, especially in certain plant species. First, strigolactones affect sensitivity to ABA, a hormone that has been proven important for drought escape (Riboni et al., 6The number of open questions regarding the functions of strigolactones in stress acclimation are undoubtedly still more numerous than the ones we have answered so far. Nonetheless, it appears clear that strigolactones do play a pivotal role in potentially all main codified aspects of the process Figure . It may


To the Editor1 the authors pulled together 20 clinical trials for a total of 4384 patients with resectable locoregional esophageal cancer.1 suggested that neoadjuvant chemoradiation followed by surgery (NCRT + S) may be the most efficient neoadjuvant treatment for resectable locoregional esophageal cancer. At the same time, the authors highlight that NCRT + S may increase the risk of postoperative mortality, but not morbidity.The optimal perioperative treatment for resectable locoregional esophageal cancer is uncertain and several questions remain unanswered in this setting. In the current systematic review and network meta‐analysis (NMA) published by Bao et al.,1 performed Bayesian NMA to optimize data extrapolation and to compare different treatments when no direct comparative trial was available and to obtain more precise effect estimated by jointly considering direct and indirect comparisons.Bao et al.However, we believe some methodological issues would deserve discussion.First, Bayesian NMA—similarly to pairwise meta‐analysis—may be associated with the inflation of false‐positive (type 1) and false‐negative (type 2) errors; because these specific errors have been suggested to play an important role to validating true‐positive as well as true‐negative findings in meta‐analyses, this issue should be carefully considered.In our view, Bao et al. are to be commended for this interesting NMA aimed at evaluating a timely topic in resectable locoregional esophageal cancer. At the same time, Bayesian NMA has some limitations that should be considered and cannot replace head‐to‐head clinical trials comparison. Based on these premises, the NMA by Bao and colleaguesWe invite the authors to share their view on these remarks.This research received no financial support.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All authors contributed to the article and approved the submitted version.


Forest tree communities are largely structured by interactions between phenotypes and their environments. Functional traits have been popularized as providing key insights into plant functional tradeoffs. Similarly, tree crown—stem diameter and tree height—stem diameter allometric relationships are likely to be strongly coordinated with functional trait tradeoff axes. Specifically, species with functional traits indicative of conservative strategies  should be related to tree architectures that have lower heights and wider crowns for a given stem diameter. For example, shade‐tolerant species in tropical forests are typically characterized as having dense wood, large seeds, and relatively broad crowns at early ontogenetic stages. Here, we focus on 14 dominant dicot tree species in a tropical forest. We utilized hierarchical Bayesian models to characterize species‐specific height and crown size allometric parameters. We sampled from the posterior distributions for these parameters and correlated them with six functional traits. We also characterize the expected height and crown size for a series of reference stem diameters to quantify the relationship between traits and tree architecture across size classes. We find little interspecific variation in allometric slopes, but clear variation in allometric intercepts. Allometeric height intercepts were negatively correlated with wood density and crown size intercepts were positively related to wood density and seed mass and negatively related to leaf percent phosphorus. Thus, interspecific variation in tree architecture is generated by interspecific variation in allometric intercepts and not slopes. These intercepts could be predicted using a handful of functional traits where conservative traits were indicative of trees that are relatively short and have larger crown sizes. This demonstrates a coordination of tropical tree life histories that can be characterized simultaneously with functional traits and tree allometries. The ontogenetic trajectory of height and crown allocation of tropical trees is an essential indicator of their life histories. Here, we show that this whole plant strategy can be linked to organ‐level plant functional traits leading to insights into how phenotypes are integrated. TA key question in community ecology has been the extent to which these fundamental tradeoff axes or trait spectra are coordinated  and fast resource acquisition rates. Previous work has indicated that, indeed, wood density does predict tree allometric relationships in tropical rainforest trees  what allometric parameters are variable among species thereby allowing for diversity in tree architecture? (ii) are functional traits that are related to where a species lands on an acquisitive to conservative ecological strategy related to allometric parameters? and (iii) are the changes in tree architecture  across trunk diameter sizes related to functional traits?22.1The present study was conducted in the area around the El Verde Field Station (350 m a.s.l.) located in the El Yunque National Forest on the island of Puerto Rico. The forest is classified as a subtropical wet forest receiving around 3.5 m of rainfall per year. The first 4 months of the calendar year are drier, but no <0.2 m of rain falls during any of these months . Only healthy trees with no evidence of structural damage were chosen and only trees where crowns could be viewed with confidence via binoculars were chosen. After tree diameter measurement, we used binoculars to identify the location of the crown edge, position themselves under that edge and use a laser range finder or tape measure to measure the distance to the tree stem. Next, the canopy edge at 90 degrees from the first measurement was taken using the same methodology. An average of these two measures was used in subsequent analyses. The height of each tree was then measured using the laser range finder. We only utilized trees where there was a clear line of sight to both the base of the trunk and top of the tree.2.33), leaf area (cm2), specific leaf area , and seed mass (g). The leaf %N, leaf %P, and SLA values indicate where species fall along a fast‐to‐slow strategy continuum where species with high values have higher rates of photosynthesis at the cost of shorter leaf lifespans, whereas species with lower values have longer leaf lifespans  is the DBH of individual i in species j. The average tree crown radius was modeled as:μi,j is the expected log10 crown radius of individual i in species j, αj and βj are the intercept and slope for species j, and log10 (DBH) is the DBH of individual i in species j. In both models, a covariance between αj and βj parameters was included. The models were evaluated using STAN via the rethinking R package  for each functional trait and allometric intercept and slope. The contrasts were calculated using a previously published phylogenetic tree containing all species in our study built using DNA barcode data  by sampling from the posterior distributions for the allometric equations for each species. This was repeated 10,000 times and the expected height and crown radius for a species at the reference diameter was correlated with their trait values to determine the sizes at which a trait predicts tree architecture. We found that only wood density predicted the expected height of the trees studied and this only occurred between reference trunk diameters of 1–5 cm Figure . That is4The present research sought to elucidate whether coordination between tree allometries and functional traits exist. We focused on 14 dominant tree species in a tropical rain forest that experiences repeated tropical storms and hurricanes that may select for species with coordinated trait axes and allometries. The results show that species vary in their allometric intercepts, but they did not vary in their allometric slopes for both height–trunk diameter and crown radius–trunk diameter relationships. The variation in allometric intercepts and not slopes indicates that interspecific differences in tree architecture in this forest are due to intercepts and not interspecific differences in the proportional increase in height or crown size for a given trunk diameter increase. Lastly, the interspecific variation in allometric intercepts and overall tree architecture across sizes could be predicted by a handful of functional traits. In the following, we discuss these results in detail.4.1Tabebuia heterophylla, Cordia borinquensis, and Manilkara bidentata were distinguishably lower from that of Casearia arborea. In other words, the first three species are shorter for smaller trunk diameters than C. arborea . There was very little interspecific variation in the slopes of the crown radius–DBH and height–DBH relationships. Accordingly, functional traits were not related to these slopes Table . In otheThere was clear interspecific variation in allometric intercepts and these could be predicted upon the basis of functional traits. The intercept of the height‐DBH allometry was negatively related to wood density Table . In othe4.3The final focus of this study was to quantify whether traits were related to overall tree form across ontogeny. To accomplish this, we sampled from the posterior distributions of the allometric models and predicted the height and crown radius of trees across reference stem diameters 1–19 cm in increments of 2 cm. The expected height of a tree species could only be predicted by wood density at the three smallest stem diameter classes ; formal analysis ; writing – original draft ; writing – review and editing . Nathan G. Swenson: Conceptualization ; data curation ; formal analysis ; funding acquisition (lead); investigation ; resources ; writing – original draft (lead); writing – review and editing .The authors declare no conflict of interest.


Hemorrhagic pancreatic fluid collections (hPFC) are a complication of pancreatitis with an unknown influence on prognosis. Advancements in endoscopic management of PFC have improved results over their surgical and percutaneous alternatives. We performed a propensity‐matched analysis comparing clinical outcomes in hemorrhagic and non‐hemorrhagic PFC (nhPFC).From November 2015 to November 2021, a retrospective comparative cohort analysis was performed comparing clinical outcomes for patients with hPFC and nhPFC managed with lumen‐apposing metal stents. Propensity score matching was used to balance the two subgroups. Wilcoxon two‐sample tests were used to compare continuous variables and Fisher's exact test was used to compare categorical variables. Kaplan‐Meier method was used to estimate overall survival.p = 0.23); however, more hPFC patients required intensive care unit admission post‐procedure . Patients with hPFC were more likely to be readmitted to the hospital within 30 days . Mortality at 3 months  and 6 months  was higher in the hPFC cohort. The 1‐year survival estimate was 73.3% (standard error = 11.4) in the hPFC group and 88.9% (6.1) in the nhPFC group (p = 0.16).Fifteen patients with hPFC were matched with 30 nhPFC patients. Technical and clinical success was similar in both groups. The median length of hospitalization was 6 days in the hPFC group and 3 days in the nhPFC group (Patients with hPFC are more likely to be readmitted to the hospital within 30 days and have worse clinical outcomes. Pancreatic fluid collections (PFC) result from acute and chronic pancreatitis during which inflammation compromises gland integrity causing pancreatic juices to leak into the surrounding tissues. These collections are associated with various complications including infection, biliary obstruction, gastric outlet obstruction, hemorrhage, or rupture.Between November 2015 and November 2021, a retrospective analysis of a prospectively maintained database was performed on all patients who underwent endoscopic ultrasound‐guided drainage of PFC using lumen‐apposing metal stents (LAMS). Institutional Review Board approval was obtained (IRB 00035936). Endoscopic drainage was performed for patients with symptomatic PFC. These symptoms included abdominal pain, gastric outlet obstruction, biliary obstruction, early satiety, and organ failure. All patients who underwent drainage of PFC using LAMS were classified into two groups differentiated by the presence or absence of hemorrhage identified on cross‐sectional imaging (diagnosed as a collection with a density of 50–100 Houndsfield units) and/or endoscopic ultrasound.All patients with hPFC underwent computed tomography (CT) angiogram to assess the presence of pseudoaneurysm prior to endoscopic drainage. Selective angioembolization was performed if a pseudoaneurysm was identified Figure  and PFC Technical success was defined as the successful deployment of LAMS into the cyst cavity. Clinical success was defined as a decrease in the size of PFC to less than or equal to 2 cm at the time of LAMS removal with a resolution of symptoms. Recurrence of PFC was defined as increasing the size of the prior drained collection (greater than 2 cm) on subsequent imaging. Follow‐up duration was measured from the time of LAMS placement to the most recent clinic visit with a gastroenterologist. Adverse events were recorded and graded with the American Society of Gastrointestinal Endoscopy Lexicon criteria.Secondary endpoints included length of hospitalization, length of intensive care unit (ICU) stay, in‐hospital mortality, mortality at 3 and 6 months, 30‐day hospital readmission rate, and overall survival. The criteria for admission or readmission following discharge were the need for medical care that could not be provided as an outpatient. This included patients with symptoms related to their collection including but not limited to intractable abdominal pain requiring intravenous analgesia, evidence of hemodynamic instability, concern for infection requiring intravenous antibiotics, sepsis, single organ or multiorgan failure, and intractable nausea and vomiting secondary to gastric outlet obstruction. Patients were discharged after the procedure if none of the above criteria were present. ICU stay was defined as a patient admitted to the hospital under the care of an intensive care specialist with options for mechanical ventilation or vasopressor support.Descriptive statistics were used to compare the two groups (hemorrhagic and non‐hemorrhagic). Propensity score matching employing a greedy‐matching algorithm and no replacement was used to balance the hemorrhagic and non‐hemorrhagic patients in a 1:2 fashion. The balanced samples were compared using Fisher's exact test for categorical measures and Wilcoxon two‐sample tests for continuous outcomes. The Chi‐square approximation of the log‐rank test was used to assess differences between groups in survival outcomes. The Kaplan‐Meier method was used to estimate overall survival in the propensity score‐matched cohorts. Statistical analysis system  was used for all analyses.There were 5277 patients diagnosed with acute pancreatitis during the study period. Of the 113 patients who underwent endoscopic management of symptomatic PFC using LAMS, 15 (12.6%) were found to have hemorrhagic collections. A pseudoaneurysm was diagnosed on a CT angiogram in two patients who underwent interventional radiology‐guided angioembolization prior to endoscopic drainage. By propensity score matching at a ratio of 1:2, the hPFC patients were matched with 30 patients from the nhPFC group (98 patients) resulting in a total of 45 patients . The median index procedure time was 43 min in the hPFC group compared to 42 min in the nhPFC group (p = 0.81). The median number of necrosectomies for patients with hemorrhagic PFCs was 1 . For non‐hemorrhagic collections, the median number of necrosectomies was 1.5 . The p‐value comparing necrosectomies for hPFC and nhPFC was 0.41. The median duration of LAMS placement was similar between the two groups . The median length of hospitalization was 6 days in the hPFC group and 3 days in the nhPFC group (p = 0.25); however, more hPFC patients required ICU admission post‐procedure . The median ICU length of stay was 8 days for hPFC compared to 4 days for nhPFC (p = 0.40). The outcomes of patients are summarized in Tables All patients in both propensity‐matched cohorts achieved technical success (p > 0.99). The single patient in the hPFC group without clinical success died prior to LAMS removal due to multiorgan failure secondary to infected walled‐off necrosis refractory to endoscopic drainage. This patient was not escalated to surgical step‐up due to poor candidacy in the setting of multiple comorbidities. Of the two clinical failures in the nhPFC group, one patient passed away from multiorgan failure despite dual‐modality drainage and escalation to open surgical necrosectomy. The other patient was successfully managed with surgical step‐up.Clinical success was achieved in 14 (93%) hPFC patients and 28 nhPFC patients  at the site of LAMS placement. The second patient developed UGIB after LAMS placement secondary to impingement of the stent on the apposing cyst wall causing bleeding and requiring epinephrine injection. In both patients, the LAMS were removed and replaced with double pigtail plastic stents. In the nhPFC group, there were five adverse events. Three patients had persistent fever following stent placement which was concerning inadequate drainage. On repeat endoscopy, necrotic material occluding the stent was seen. All three patients were treated with IV antibiotics and required endoscopic necrosectomy with the resolution of symptoms. One patient had an upper gastrointestinal bleed secondary to a pseudoaneurysm in the splenic artery requiring angioembolization. The last patient had postoperative abdominal pain due to smoldering pancreatitis requiring admission, intravenous fluids, and analgesics.p = 0.28), the median length of follow‐up , in‐hospital mortality , 3‐month mortality , and 6‐month mortality  did not reach statistical significance. However, when comparing post‐discharge 30‐day readmission rates, hPFC patients were more likely to be readmitted to the hospital . Intensive care unit readmission was seen in two patients in the hPFC group and none in nhPFC (p = 0.11). A comparison of adverse outcomes between hPFC and nhPFC collections is summarized in Table p = 0.16)  Figure .hPFC result from autodigestion of blood vessels from pancreatic enzymes causing weakening of the vessel walls. These collections, which develop as a complication of pancreatitis, have an unclear influence on clinical outcomes. Recent advances in endoscopy have shown benefits to minimally invasive approaches in the management of PFC; however, extrapolation of these results to hemorrhagic collections is largely unknown.The underlying pathophysiology of acute pancreatitis complicated by bleeding is unique and distinctly different from acute pancreatitis.  Factors that contribute to worse outcomes associated with bleeding include coagulopathy, severe inflammatory state, severe protein deficiency, and systemic anticoagulation in patients with comorbidities such as cardiac arrhythmia. In addition, hemorrhagic PFC likely result in hemostatic dysequilibrium with procoagulant and antithrombotic factors contributing to anemia and poor clinical outcomes.  Our study demonstrates that endoscopists should be cognizant of intracystic hemorrhage as it likely yields worse outcomes. There was a statistically significant increase in 30‐day readmission rates amongst patients with hemorrhagic collections. In addition, patients in the hPFC group had a longer length of hospital stay, an increased likelihood of intensive care admission post‐procedure, and a higher 3‐ and 6‐month mortality; however, the analysis did not reach statistical significance. The clinical significance of these findings should not be understated. These results demonstrate that patients with hPFC are more likely to decline and have a more severe clinical course than their counterparts warranting close observation.A standardized diagnostic and management algorithm is essential for the endoscopic management of hPFC. This includes CT angiography to assess the need for angioembolization of a pseudoaneurysm prior to endoscopic therapy. Endoscopic drainage of hPFC using LAMS provides a safe and effective alternative to surgical interventions, similar to non‐hemorrhagic PFC. However, due to the complexity of these collections and the risk of readmission, a multidisciplinary approach is warranted. Furthermore, patients may benefit from the close follow‐up to ensure the stability of the collection. This approach should promote improved outcomes, prevent patient morbidity, and ensure the safe resolution of the collection.The existing literature on the management of intracystic hemorrhage is limited to a small collection of case series and case reports without long‐term follow‐up. Most of the reported cases in the literature have focused on surgical management of hPFC which has recently been supplanted by endoscopic and interventional radiology interventions due to their lower morbidity and mortality.The strengths of this study include its standardized approach to managing the subjects. In addition, all patients were managed by a multidisciplinary team with regular imaging obtained at the same institution. This eliminated the concern for variability in imaging quality. Furthermore, all patients were followed for at least 6 months with a gastroenterologist ensuring the capture of relevant clinical outcomes.Our study is not without limitations. First and foremost, only 15 patients were identified during the study period to have hemorrhagic collections which limited the power of the analysis and likely underestimated the importance of hPFC. In addition, the presence of hemorrhage was identified by the endoscopist prior to drainage; therefore, treatment bias is a concern as this could have led to a more conservative management approach. In addition, all procedures were performed upon consultation with a multidisciplinary team including advanced therapeutic endoscopists, a hepatobiliary surgeon, and abdominal radiologists at a large tertiary care facility. This may prevent the extrapolation of these findings to all institutions.In conclusion, our findings show that hPFC warrant close attention due to their impact on clinical outcomes. Larger studies are indicated to examine the significance of hPFC.Dr Rishi Pawa is a consultant for Boston Scientific. Dr. Girish Mishra is a consultant for Cook Endoscopy and Pentax Medical.